description
stringlengths 2.59k
3.44M
| abstract
stringlengths 89
10.5k
| cpc
int64 0
2
|
|---|---|---|
This is a division, of application Ser. No. 486,583, filed July 8, 1974, and now U.S. Pat. No. 3,890,691.
BACKGROUND OF THE INVENTION
Apparatus for hydro-therapeutic treatment, for example to carry out massages by water or in water with the aid of natural water, mineral water, sea water or water mixed with appropriate products or a gas are known in the art. Such massages may be applied manually by the operator by means of a jet of water under pressure, or by injection of water and gas under pressure through a plurality of jets installed in the apparatus through a plurality of orifices or appropriate nozzles which may be provided in the wall of the apparatus disposed in such a manner that the water under pressure passes through the orifices or nozzles to thus provide a massage. Usually the water or liquid is recycled by means of a pump which sucks the water from the vessel of the apparatus and recirculates the water through the aforementioned orifices or nozzles.
Thus it is often necessary to provide a vessel with a double wall provided with circulation channels for the water under pressure to feed this water to the aforementioned orifices or nozzles of injection into the interior of the apparatus that is the main trough of the same.
The methods so far known for providing such an apparatus are not adapted to provide a great number of orifices or nozzles through which water may be injected into the main trough or vessel of the apparatus due to the difficulty of construction of the body of such apparatus which may be formed from cast-iron, plastic material or other suitable materials.
Summary of the Invention
It is an object of the present invention to provide a method of forming an apparatus of the aforementioned kind which avoids the difficulties of known methods according to the prior art.
It is an additional object of the present invention to provide a method in which the nozzles are arranged that in addition to water under pressure also an appropriate auxiliary fluid may be injected therethrough, in which the nozzles are fixed in a particular manner to the remainder of the apparatus and in which a channel integral with the wall of the main vessel or trough of the apparatus is provided with which the aforementioned nozzles communicate so that water fed under pressure in the channel is injected through the nozzles into the main vessel of the apparatus.
With these and other objects in view, which will become apparent as the description proceeds, the method according to the present invention of producing an apparatus for hydro-therapeutic treatment having a vessel provided with a channel of integral double-walled structure mainly comprises the steps of providing a mold having a wall with an outer surface corresponding to the inner surface of the vessel to be produced and being formed in the wall thereof with a row of apertures, in which the mold is placed on a support with the outer surface thereof facing upwardly, whereafter in each of the aforementioned apertures an insert is fixed projecting beyond the outer surface of the mold wall. A first layer of hardenable or polymerizable plastic material is then applied onto the outer surface of the mold wall with the aforementioned inserts projecting beyond the outer surface of this first layer. An elongated plug of meltable or dissolvable material having the form of the channel to be produced and provided with a row of passages is then placed on each row of inserts with the latter respectively projecting through and beyond the passages and an additional layer of plastic material is then applied onto the free outer surface of the aforementioned plug while the first layer is still in plastic condition so that the additional layer is integrally joined to the first layer. After the layers have hardened, the inserts are removed to provide in the layers openings corresponding to surface portions of the inserts. Subsequently thereto the plug is removed by melting or dissolving the material thereof, and nozzle members having outer surface portions identical with the surface portions of the inserts are then placed into the openings previously occupied by the inserts and fixed axially immovably at opposite ends to the first and the additional layer.
The apparatus thus produced is especially characterized in that the nozzles are axially immovably fixed in the channel of integral double-wall structure.
The material from which the vessel and the channel of double-walled structure is formed is preferably a polymerizable compound of polyester and glass fibers applied to the mold and the plug for instance by spraying with a spray gun.
The novel features which are considered as characteristic for the invention are set forth in particular in the appended claims. The invention itself, however, both as to its construction and its method of operation, together with additional objects and advantages thereof, will be best understood from the following description of specific embodiments when read in connection with the accompanying drawing.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a longitudinal cross-section through a mold for forming the vessel of the apparatus in form of a bath tub;
FIG. 2 is a longitudinal cross-section through part of the hollow body or channel provided on the vessel in the region of a nozzle, and part of the mold shown in FIG. 1;
FIG. 3 is a partial cross-section through the aforementioned hollow body provided with a plurality of different nozzles;
FIG. 4 is a side view of an insert used during forming of the apparatus;
FIG. 5 is a schematic perspective view of the plug for molding the aforementioned channel;
FIG. 6 is a transverse cross-section through the aforementioned channel and provided with a nozzle communicating therewith;
FIG. 7 is an axial cross-section, shown at an enlarged scale, through a nozzle provided with a first passage inclined to the nozzle axis and a second passage extending along the nozzle axis for the respective passage of a fluid under pressure and an auxiliary fluid;
FIG. 8 is an axial cross-section, likewise shown at enlarged scale, of a different nozzle provided with only one passage therethrough; and
FIG. 9 is an axial cross-section through a manifold to be connected to the axial passages of a plurality of nozzles as shown in FIG. 7 for supplying the same with air or another gas.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1 illustrates a longitudinal cross-section through a hollow thin-walled mold 1 used for forming the vessel in form of a bathtub. The mold 1 is placed with its open end, as shown in FIG. 1, on a table or similar support 1a. The mold 1 has an outer surface corresponding to the inner surface of the vessel to be produced and is formed in a portion of its wall with one or a plurality of rows of openings 2 spaced in longitudinal direction from each other. The mold is preferably formed from polyester reinforced with glass fibers and it is carefully covered on the outer surface thereof with a film of material preventing adherence of the material to be applied to the mold to the latter. A plurality of inserts 3 of frustoconical configuration, as best shown in FIGS. 2 and 4, are then coaxially fixed at each opening 2 to the mold 1 by screws 4 respectively extending through the openings 2 and screwed into correspondingly threaded axial bores of the insert 4. A washer 4a is preferably sandwiched between the head of each screw and the inner surface of the mold 1. The inserts 3 are preferably made of Teflon or similar material which will assure that the material from which the vessel of the apparatus is formed will not stick to the insert. The wall 7 of the vessel, only partly shown in FIGS. 2 and 3, is preferably applied to the mold 1 by spraying, through a spray gun, a polymerizable mixture of polyester and glass fibers, which may be colored before spraying to any color desired. A first layer 7 of the aforementioned material is thus applied to the outer surface of the mold 1 with the inserts 3 projecting beyond this first layer. Each of said inserts has at one end, abutting against the outer surface of the mold 1, a frusto-conical end portion 3a of a larger cone angle than the main portion of the insert so as to properly anchor each insert in the first layer 7, and each insert has at the other end thereof a portion 3b of smaller diameter. An elongated plug 9 of the form as best shown in FIG. 5, molded with a row of holes or passages 9a passing therethrough, spaced from each other in the longitudinal direction of the elongated plug, is then placed on the first layer 7 with the inserts 8 respectively projecting through the holes 9a and with the portions 3b of each insert projecting beyond the upper surface of the plug 9. The plug 9 has an outer surface corresponding to the inner surface of the channel to be formed on the layer 7. The elongated plug 9 is a so-called "lost plug", that is, it is formed of material liable to melt, to disintegrate or to be dissolved in the presence of heat, water or an appropriate other solvent. The material from which the plug may be formed may be, for instance, bee wax or paraffine. The plug 9 may terminate at one end thereof with a cylindrical projection 9b onto which a, preferably metallic, tube 10, as shown in FIG. 3, is placed. Subsequently thereto an additional layer 8 of a plastic polymerizable compound which may have the same composition as the layer 7 is applied to the free outer surface of the plug 9 and around the tube 10, while the first layer 7 is still in plastic condition, so that the additional layer 8 is integrally joined to the first layer 7. The inserts 3 project with portions of the portions 3b beyond the additional layer 8, as shown in FIG. 2 and so does the outer end of the metallic tube placed onto the cylindrical projection 9b of the plug 9. A washer 5 is fixed by a snap ring 6 engaged in a corresponding groove to the projecting portion 3b of each insert so that the bottom face of the washer engages the upper surface of the additional layer 8 to maintain during the complete polymerization or hardening of the plastic material the outer surface of the additional layer 8 at a fixed distance L from the bottom face of the layer 7.
Subsequently thereto the screws 7 are unscrewed from the inserts 3, the vessel formed by the layer 7 is then removed from the mold 1, the snap rings 6 are removed from the grooves in the portions 3b of the inserts, the washers 5 are removed, and the inserts 3 withdrawn. Subsequently thereto the plug 9 is destroyed by rendering its materials flowable by heating, injection of hot water or a solvent and discharging the material through the various openings in the layers 7 and 8 to thus obtain the desired channel with openings and conical seats into which subsequently thereto the nozzles 20 or 21 of a shape as respectively shown in FIGS. 7 and 8 are inserted. Each of the nozzles 20 and 21 is provided at one end thereof with a frustoconical portion 22 of the same cone angle as the portion 3a of each insert and a portion 23 of the same cone angle of the main portion of each insert 3. An annular groove 24 is provided between the frustroconical portions 22 and 23. A stem 25 of the nozzle 20 (shown in FIG. 7) projects coaxially from one end of the frustoconical portion 23 and this stem 25 is provided adjacent its free end with an outer screw thread 26. A passage 15 inclined to the axis of the stem 25 extends through the portion 23 of the nozzle 20 and terminates at the end face 22a of the nozzle with a passage portion 16 of a slightly larger diameter than the passage 15, and an additional passage 17 extends coaxially through the stem 25 and the portion 23 communicating at one end thereof with the passage portion 16.
The nozzle 21 shown in FIG. 8 is provided with a central solid stem 27 provided at its free end with a screw thread 28. The nozzle 21 is formed with a single passage therethrough having a passage portion 28 extending transverse to the stem axis and a passage portion 29, communicating therewith and arranged coaxially with the axis of the stem. The stems 25 and 27 of the nozzles 20 and 21 have an outer surface corresponding to an outer surface portion of the insert portions 3b. The nozzles 20 or 21 are inserted through the openings formed in the walls 7 and 8 by the previously inserted inserts, in the manner as best shown in FIG. 3, so that the passages 15 or 28 and 29 communicate with the interior of the channel provided between the walls 7 and 8. A sealing ring 31 of compressible material is preferably placed in the annular groove 24 of each nozzle. The stem portions 26 or 27 of the nozzles project upwardly beyond the wall 8 and a nut 32 screwed onto the threaded portion 26 or 28 of the stem portions of the nozzles hold the latter axially immovable with respect to the walls 7 and 8. A washer of compressible material is preferably sandwiched between each nut 32 and the outer surface of the wall 8. The tube 10 is connected at its outer end, in a manner not shown in the drawing, to a supply of water under pressure, likewise not shown. The axial passage 17 of the nozzles 20 may be connected to passages in a manifold 34, shown in FIG. 9, which is supplied through a valve 35 with an auxiliary fluid, for instance a gas under pressure from a supply not shown in the drawing.
It will be understood that each of the elements described above, or two or more together, may also find a useful application in other types of apparatus differing from the types described above.
While the invention has been illustrated and described as embodied in an apparatus for hydro-therapeutic treatment, it is not intended to be limited to the details shown, since various modifications and structural changes may be made without departing in any way from the spirit of the present invention.
Without further analysis, the foregoing will so fully reveal the gist of the present invention that others can, by applying current knowledge, readily adapt it for various applications without omitting features that, from the standpoint of prior art, fairly constitute essential characteristics of the generic or specific aspects of this invention. | An apparatus for hydrotherapeutic treatment includes a vessel having a wall of plastic material provided at a portion of its outer surface with a channel formed by a wall integral with the vessel wall. Inlet means communicate with the channel for feeding a fluid under pressure thereinto. A plurality of nozzles extend transversely through openings in the vessel and channel walls removably fixed at opposite ends to these walls. Each of the nozzles has a passage communicating with the interior of the channel and a discharge end at the inner surface of the vessel wall. | 1 |
BACKGROUND OF THE INVENTION
I. Field of the Invention
The present invention relates to a manually arm powered swimming aid device which both supports the swimmer and also supplements the usual paddling action to help the beginning swimmer learn to swim and to provide a water toy.
II. Description of the Prior Art
There are a number of known manually arm powered swimming aids which also provide support to the swimmer. U.S. Pat. No. 1,102,526 has a flotation ring to encircle a swimmer which supports a pair of opposed paddle wheels which are operated by a manual crank. U.S. Pat. No. 1,777,749 has a pair of flotation disks which carry a number of hinged paddle elements and are interconnected by a crank. The immersed swimmer rotates the disks by the paddle wheel which provides both flotation and propulsion. U.S. Pat. No. 3,580,213 is quite similar except that the flotation elements have fixed radial elements formed into the disk but the purpose and operation is quite similar. U.S. Pat. No. 3,779,202 has a pair of paddles attached to a surfboard which are crank operated by a swimmer lying on the surfboard for support. U.S. Pat. No. 3,045,636 has a flotation structure in which the operator is seated for support with two independent opposed arm operated paddle wheels for propulsion.
All of these devices rely strictly on rotation of the paddle wheels for propulsion which bears no relationship to a normal arm swimming stroke. Those that utilize the paddle wheel solely to support the swimmer in the water are large unwieldly structures which are bulky to store and transport. Further, a large amount of the energy required to rotate a paddle wheel supporting a swimmer is wasted because when the paddle wheel is largely immersed in the water, as results when it is the sole support, the individual paddles enter and leave the water at a corresponding large angle. As a consequence, the paddle moves the water downward and rearward while entering the water and upward and rearward when leaving the water. Since only the movement of water which is rearward versus the direction of movement actually propels the swimmer, all additional energy spent in moving the water vertically is wasted and since water is a very dense medium this wasted energy is considerable.
My invention avoids these problems by permitting a swimming motion which closely mimics the normal arm motions of a swimmer to aid in more rapid learning. Only one blade is used for each paddle rather than a paddle wheel which greatly reduces storage and transportation problems. Only one blade is rotated at a time similar to an oar engaging the water while the blade motion is horizontal which eliminates waste energy in moving the water vertically and which mimics a normal swimming stroke.
SUMMARY OF THE PRESENT INVENTION
The present invention provides a manually powered pair of flat paddles which are interconnected by a crank which offsets sized to be rotated and driven by the arms of a swimmer. Two handles which are free to rotate with respect to the crank permits the swimmer to grasp the crank and exert a great deal of force with little rotation friction. Each paddle is essentially flat and is affixed to opposite ends of the crank.
The paddles are formed from a foamed plastic which solidifies into a solid with a great number of entrapped air bubbles to provide flotation. If desired, the paddles can be enclosed by a matching plastic skin to provide protection for the foamed plastic. The paddles are each formed about a pair of metal plates and have a central semicircular channel sized such that when the plates are placed opposing each other the resulting circular channel will fit about the end of the crank.
A disk shaped mechanism on each end of the crank is attached to a perpendicular extension on these metal plates. The disk shaped mechanism is arranged to encircle the crank ends when the paddles are mounted in place. A driver portion of this mechanism is keyed to the crank while a follower portion is attached to the perpendicular extensions from each of the plates. A wobble plate mounted adjacent to the plate extensions permits the driver to be vertically displaced to intermittently engage the follower by allowing a projecting cam on the driver to engage a spur on the follower when the cam is at a certain angular relationship with respect to the follower. A cover plate is secured over the mechanism and end of the crank for protection. When the driver is advanced approximately 180 degrees the follower portion of the mechanism is no longer driven to provide intermittent motion.
In use, the swimmer thrusts downward and backward with one arm and upward and forward with the other arm. The downward thrusting arm will rotate the crank and also bear downward on that side. The wobble plate is arranged to permit the end of the crank to shift to always be on the down side relative to the remainder of the mechanism. The drivers are arranged 180° out of phase such that one of the projections on the drives on the downward crank will engage the follower while the projections on the driver of the opposite end will be disengaged. When the driver engages the follower the crank will rotate the follower and the paddle on that end while the paddle on the opposite end will be disengaged and will lie flat on the water. The result will be that one paddle only will engage with the water and provide a propulsive force while the opposite paddle will lie flat and provide support only. There is little vertical movement in this stroke and consequently little wasted energy.
When the swimmer reaches the end of this stroke where the driven paddle has rotated 180 degrees and is lying flat in the water with the drivers both rotated 180° the engagement will reverse ends and will permit the driver on the opposite end to engage the follower to repeat the stroke on the opposite side while the first end driver will be disconnected.
While some rotation motion of the swimmer's arms is still necessary to operate this device an alternate rowing motion of the arms is also required which much more closely approximates the normal use of the arms in swimming. The water is driven horizontally which makes this device very efficient.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of the apparatus in use.
FIG. 2 is a top view of the apparatus with the left paddle in phantom outline.
FIG. 3 is a cross-section 3--3 of FIG. 2.
FIG. 4 is a perspective view of a portion of the mechanism enlarged with the mechanism engaged.
FIG. 5 is the view of FIG. 4 with the mechanism disengaged.
FIG. 6 is a plane view of a driver.
FIG. 7 is a plane view of a wobble plate.
FIG. 8 is a cross-section side view of the mechanism and a portion of adjacent parts.
FIG. 9 is a plane view of a follower.
FIG. 10 is a plane view of a spacer washer.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to the drawings FIGS. 1-9 illustrate a preferred embodiment of this apparatus. FIG. 1 illustrates a swimmer 5 using swimming device 10 in the water. In this figure swimmer 5 is thrusting forward with his right hand and pulling with his left hand to rotate the device in the direction indicated by the arrows. Paddles 12 are mounted on opposite ends of crank 16 but here only the left paddle relative to the starter is being rotated while the right paddle rests flat in the water.
Crank 16 has two free turning handles 18 to permit swimmer 5 to turn the crank freely. Handles 18 are limited in their horizontal movement along crank 16 by the offsets adjacent to the handles of the crank which can be seen more clearly in FIG. 2.
Here leftmost paddle 12 is shown in phantom outline with the inner structure revealed. The outer structure of paddle 12 is formed from plastic liquids which are foamed and set into a solid and which is formed by a mold into the shape illustrated.
In FIG. 3 the cross-sectional end view of the interior of paddle 12 can be seen. A plastic skin 22 which covers and protects foam 20 is secured in place after the foam is set by gluing two plastic skin halves together each having the same interior shape as the exterior of the foam. Two generally flat metal plates 24 each have a semi-circular center section to enclose crank 16. Each plate 24 has an integral peripheral projection 23 at the outside edge to engage the remainder of the mechanism using holes 25 as will be described later.
In FIGS. 6, 7, 9, and 10 parts of mechanism 14 are shown. FIG. 6 is a plane view of a driver 26 with a projecting cam 27 which is used to alternately couple power from crank 16 to paddle 12. A vertical integral cylinder 28 extending from driver 26 is sized to fit about the end of crank 16. A pair of aligned holes 30 perpendicular to cylinder 28 are sized to receive a pin, not shown, which is used to key driver 26 to crank 16.
In FIG. 7 wobble plate 32 is shown which has an elongated center hole 34 and two mounting holes 36. In FIG. 9 follower 38 is shown having two opposing inwardly directed spurs 40 and mounting holes 42 which are the same size and spacing as mounting holes 36 in FIG. 7. In FIG. 10 a washer 43 with mounting holes 45 is shown.
In FIG. 8 mechanism 14 is shown mounted on one end of crank 16. The opposite end of crank 16 has the same mechanism 14 mounted as here but with the drive mechanism 180° out of phase with respect to the crank. A metal cover plate 44 is secured over the end of crank 16 which has a stamped cupped center to accomodate the projecting end of the crank. Cover plate 44 encloses the operating parts of mechanism 14 to keep foam plastic liquids out during manufacture and to keep lubricant in during use. Two mounting holes through cover plate 44 are of the same size and spacing as mounting holes 36 in wobble plate 32, shown in FIG. 7.
Mechanism 14 is assembled with cover plate 44 leftmost then washer 43 then follower plate 38 encircling driver 26 then wobble plate 32 with all parts mounted around the end of crank 16. Bolts 46 through the mounting holes in cover plate 44, mounting holes 45 in washer 43, mounting holes 42 in follower plate 48, mounting holes 36 in wobble plate 32 and holes 25 in projections 23 extending from plates 24 are all secured by nuts 48 to hold mechanism 14 together and attach it to plates 24. A key 50 through holes 30 in cylinder 28 and a matching aligned hole in crank 16 keys driver 26 to the crank. Washer 43 keeps the edges of driver 26 aligned with follower plate 38. A sleeve bearing 52 mounted around crank 16 minimizes friction, shown in FIG. 4.
In FIGS. 4 and 5 the operation of the various parts of mechanism 14 is shown. In FIG. 4 crank 16 is being rotated counterclockwise as viewed from the left end and handle 18 is horizontal in the stroke and being forced downward. In this view cover plate 44 and washer 43 are omitted to give a better view of the remainder of mechanism 14. At this part of the cycle elongated center hole 34 in wobble plate 32, not shown, is oriented with the long dimension vertical which permits the end of crank 16 to move downward with respect to plates 24. This occurs because plates 24 are supported by paddle 12, not shown in this figure, being supported by water. This relative vertical motion permits cam 27 to engage spur 40 on the bottom of follower 38 which will cause plates 24 and associated paddle 12 to rotate. At the same time the opposite end of crank 16 is in the relationship with hole 34 in wobble plate 32 also oriented with the long dimension vertical but since driver 26 is keyed 180 degrees out of phase the driver will be disconnected from the follower, as will be explained later.
Whereas before in FIG. 4 the lower edge of cam 27 was aligned with spur 40, which caused follower 38 to be rotated by driver 26, now 180 degrees later, as shown in FIG. 5, with crank 16 again at the lower position cam 27 will clear upper spur 40 allowing free rotation of crank 16 in the direction shown. This will decouple shaft 16 from plate 24 and from the enclosing paddle 12. In the position between FIGS. 4 and 5 when the paddle 12 enclosing plate 24 passes beyond the point where the flat paddle is perpendicular to the water the buoyancy of the paddle will tend to rotate the paddle to the attitude shown in FIG. 5 where it will remain until driver 26 again reengages follower 38 as described earlier.
This mechanism will operate in the same way regardless of the direction of rotation in that one paddle will be driven and the other paddle free for essentially one half a revolution and then the driven and free paddles will be reversed.
Mechanism 14 thus provides a means for coupling and decoupling paddles 12 from crank 16 with each paddle alternately providing propulsion or support only. Device 10 will work with either paddle oriented on the swimmer's left or right side. There is no orientation restriction in that device 10 can merely be thrown into the water and the swimmer 5 can grasp either side and the operation will be the same.
The mechanical parts can be stamped from a number of metals or plastics and the formed center of paddles 12 can use any number of plastics well known in the art which will foam and entrap air and then solidify. This swimming aid is easy to manufacture, simple in construction and easy to store and transport. Its use will both support the beginning swimmer in the water, permit him to use his legs normally and permit him to mimic an arm swimming stroke.
While this invention has been described with reference to an illustrative embodiment, this description is not intended to be construed in a limiting sense. Various modifications of the illustrative embodiment, as well as other embodiments of the invention, will be apparent to persons skilled in the art upon reference to this description. It is therefore contemplated that the appended claims will cover any such modifications or embodiments as fall within the true scope of the invention. | A manually powered pair of crank operated flat paddles used by a swimmer combines a rotary and paddling motion. One paddle is rotated to engage the water while the opposite paddle is disengaged and provides flotation only. The opposite paddle is then rotated to engage the water while the first paddle is disengaged. This apparatus combines support with propulsion to assist the beginning swimmer. The motion of the swimmer's arms using this device mimics a normal swimming stroke and aids the learning process. | 0 |
BACKGROUND OF THE INVENTION
This disclosure relates to a method and apparatus for correcting abnormal flexion of the joints of the human foot. More particularly, this disclosure relates to a combination of dorsifexion of the metatarsal/proximal phalangeal joint and plantar flexion of the proximal interphalangeal joint, commonly called a hammer toe.
The lesser toes of the human foot are composed of three bones and contain two joints. The three toe bones are a proximal phalanx (closest to the metatarsal bone), a middle phalanx, and a distal phalanx (at the end of the toe). The three toe bones are connected by two toe joints, a proximal interphalangeal joint (PIPJ), which is formed by a distal end of the proximal phalanx and a proximal portion of the middle phalanx; and a distal interphalangeal joint (DIPJ), distal to the PIPJ and formed by a distal end of the middle phalanx and a proximal end of the distal phalanx.
Contraction of the lesser toes of the foot is a common pathologic condition due to an imbalance between the tendons on the top and bottom of the toe(s). When an affected toe is able to be straightened out manually, i.e. by an individual or an eternal force, it is referred to as a flexible hammer toe. If left untreated these flexible contractures will become a fixed deformity know as a rigid hammer toe, which cannot be put back into normal alignment. The PIPJ is more implicated in a hammer toe syndrome deformity then the DIPJ.
There are many palliative modalities such as pads and various forms of orthodigital devices used to accommodate toe deformities. Those conservative options, however, do not provide an individual with enough comfort and in some cases are simply illogical given the fact that various alternative surgical options are available.
Throughout the history of performing toe surgery many methods have been attempted by surgeons ranging from simple tendon release, partial joint excision, full joint excision and, as a final resort, complete fusion (arthrodesis) of a joint rendering a straight toe. Arthrodesis of the joint is usually reserved for severe deformities or in cases where previous non-arthrodesic procedures were performed but failed to provide a patient with desired expectations.
In the past some surgeons fused the PIPJ joint by a simple end-to-end method. In this procedure a surgeon resects the articular cartilage of the end of one toe bone and the base of an adjoining bone which forms an abnormal joint. The two ends are approximated to each other with the expectation that they will fuse together. An inherent problem with this method is a high rate of non-union with possible recurrence of deformity.
Another method is to insert a smooth pin or wire that extends out of the distal end of the toe. The wire is used to hold the ends of the bones in alignment until fusion occurs. Because these wires and pins are smooth, however, it is possible for the joint to distract leading to a failure or non-union.
Additionally, yet another method was developed which utilized a thin screw inserted from the tip of a toe across the joint. The purpose of this device was to provide compression which facilitates end-to-end fusion. The insertion of a specialized screw is difficult to perform and presents a possibility of damaging the DIPJ. Furthermore, when the pin is removed it requires a second surgical procedure.
Yet, another device was developed utilizing “memory” metal that was simply inserted into either the DIPJ or PIPJ after resection of the joint. These devices are relatively expensive when compared to pins, wires, or screws and also have been known to sometimes expand too quickly rending the device ineffective.
Finally, a hinged toe fusion device was developed to replace the PIPJ. Each end of the device was inserted into a corresponding end of the bones flanking the PIPJ. A limitation with this device is that it is relatively difficult to work with. The two components are not designed to be easily separated. Also, the device can be difficult to properly align and can rotate out of the proper position after insertion. Also, it does not allow for the additional use of a pin or wire to be inserted across the metatarsophalangeal joint (MPJ), the joint proximal to the PIPJ, which is sometimes desirable.
The difficulties and limitations suggested in the preceding are not intended to be exhaustive, but rather are among many which demonstrate that although significant attention has been devoted to surgically correcting hammer toe disfigurement, nevertheless surgical implants and procedures appearing in the past will admit to worthwhile improvement.
BRIEF SUMMARY OF PREFERRED EMBODIMENTS
The subject disclosure includes advantages of bone fusion while simplifying the procedure and decreasing or eliminating incidences of non-union and non-alignment. A preferred embodiment comprises a two-component device including (1) a proximal phalanx component and (2) a middle phalanx component. The two components are handled separately during a surgical procedure. Each is inserted axially into a respective host bone. After insertion, the components are joined. The attached components are held together in various ways, for example a detent arm/aperture mechanism. As the components are brought together, the arms of one component slide into a central channel, or cannula, in the other component. The arms are spring loaded as they first encounter an inner surface of the cannula and then spring out when the arms encounter lateral apertures present further on along the cannula. Each component can be cannulated to allow for the passage of a wire, e.g. 0.045 inch kirschner wire (k-wire), which passes through the center to stabilize either the DIPJ or the MPJ.
An interphalangeal joint implant is inserted using the following procedure. A surgeon exposes the PIPJ, separates the two bones making up the joint and then removes the articular cartilage. Next, a device, such as a trephine, is used to “core” the ends of the bones on each side of the joint. The trephine removes a central cylindrical section of bone within the bone shafts which allows for a press-fit junction of the stems of the opposing implant components. A stem of the proximal implant component is inserted into the proximal phalanx and a stem of a distal implant component is inserted into the middle phalanx. These endosseous stems preferably are non-cylindrical in shape. This will inhibit unintended rotation of the implant after insertion. If stabilization of an adjacent joint is required a k-wire can be directed from within the joint out through the tip of the toe making certain that the proximal end of the wire will not prevent the fastening together of the two implant components. The middle phalanx portion would then be fitted to the proximal phalanx portion and then the k-wire can be passed through the MPJ.
THE DRAWINGS
Numerous advantages of the present disclosure will become apparent from the following detailed description of preferred embodiments taken in conjunction with the accompanying drawings wherein:
FIG. 1 is an axonometric view of a context of the disclosure comprising a front portion of a human foot with some flesh removed from a lesser second toe to illustrate severe plantar flexion of the proximal interphalangeal joint (“PIPJ”) reflecting a rigid joint deformity commonly known as hammer toe;
FIG. 2 is an axonometric view of an interphalangeal joint implant in accordance with a preferred embodiment of the invention;
FIGS. 3A-3B are axonometric views of individual proximal and distal components of the interphalangeal joint implant depicted in FIG. 2 ;
FIG. 4 is a cross-sectional view taken along section line 4 - 4 of FIG. 2 ;
FIGS. 5A-5B are cross-sectional views taken along sections line 5 A- 5 A and 5 B- 5 B in FIGS. 3A and 3B , respectively;
FIG. 6 is a cross-sectional view taken along section line 6 - 6 in FIG. 2 ;
FIGS. 7A-7B are a side views taken along section lines 7 A- 7 A and 7 B- 7 B in FIGS. 3A and 3B , respectively;
FIG. 8 is a top view of the interphalangeal implant shown in FIG. 2 ;
FIG. 9 is a side view of the interphalangeal implant depicted in FIG. 8 .
FIG. 10 is a top view of an alternative preferred embodiment of the interphalangeal implant;
FIG. 11 is a side view of the interphalangeal implant depicted in FIG. 10 illustrating one of the endosseous stems with an imaginary central longitudinal axis offset from the other stem's axis by a distance “A,” and by an angle Theta (θ); and
FIGS. 12A-E illustrate, in schematic format, a procedure for correcting a misaligned PIPJ ( FIG. 12A ) where the bones flanking the PIPJ are separated ( FIG. 12B ), tissue around the PIPJ is removed ( FIG. 12C ), the implant components are inserted, one into each of the bones flanking the PIPJ ( FIG. 12D ), and the components of the implant are joined into an integrated unit ( FIG. 12E ).
DETAILED DESCRIPTION
Context of the Invention
Referring now particularly to the drawings, wherein like reference characters refer to like parts, and initially to FIG. 1 , there will be seen a schematic illustration of a context of the subject disclosure—a misaligned interphalangeal joint commonly referred to as a “Hammer toe.”
The disclosure is directed to correction of misalignment between virtually any two bones, but particularly for the flange bones that make up the five digits of the foot and hands. A typical bone misalignment is illustrated in FIG. 1 , with flesh removed from a second toe for illustrative purposes. Depicted are a metatarsal 100 , proximal phalanx 102 , middle phalanx 104 and distal phalanx 106 bone segments in a human foot. As noted above, FIG. 1 illustrates a hammer toe condition characterized by dorsifexion of the metatarsal/proximal phalangeal joint 108 and plantar flexion the proximal interphalangeal joint (“PIPJ”) 110 . The subject apparatus and procedure are directed to correction of this abnormal flexion of the PIPJ. Although the subject disclosure is directed in particular to medically correcting hammer toe syndrome it is also useful for more curved or claw toe maladies as well. In this sense the term hammer toe as used herein includes claw toe, mallet toe and curly toe conditions. The disclosure also applies to analogous conditions affecting human fingers.
Interphalangeal Joint Implant
FIG. 2 illustrates an axonometric view of the device with two component parts operably joined together. FIG. 3A is the proximal phalanx component and FIG. 3B is the middle phalanx component of a human second toe.
The proximal phalanx component 112 , FIG. 3A , is designed to be inserted into the distal end of the proximal phalanx. It comprises an endosseous stem 114 , 116 and a base 118 . The stem is either cylindrical, non-cylindrical or a combination of the two. A non-cylindrical shape has the advantage that the stem will not easily rotate after insertion into the proximal phalanx. The component 112 illustrated in FIG. 3A combines a cylindrical portion 114 at the tip of the stem and a non-cylindrical, oval or regular trapezoidal portion 116 at the base of the stem. The shape need not be oval or regular trapezoidal. Any shape that is non-spherical in cross-section will function to inhibit rotation of the device once it is inserted into the bone. Other measures can be employed to inhibit or prevent rotation such as the use of adhesives or surgical cement. Also, the device can be designed to screw into place provided one insures that the device will be in the proper orientation when the base of the device contacts the end of the bone.
Other structures can be added to the device to inhibit an untended tendency for the device to loosen or slide out from the end of bone. For example, the device can have regular or irregular surface protrusions. Alternatively, the surface of the stem can have various structures and shapes that promote tissue in growth such as interstitial spaces, ribs, channels, holes, grooves and the like.
The proximal phalanx component 126 also contains a base 128 . When the component is fully inserted, the base will be flush against the distal end of the proximal phalanx, in position to contact the corresponding base of the middle phalanx component illustrated in FIG. 3B .
The base can be equipped with a registry structure that will insure the bases, FIG. 3A and FIG. 3B , will properly align when brought into contact. A preferred registry structure is illustrated in FIG. 3A , two pins 120 that interact with correspondingly shaped circular cavities 136 in the base 128 of the middle phalanx component illustrated in FIG. 3B .
The middle phalanx component, FIG. 3B , designed for insertion into the proximal end of the middle phalanx, will be generally smaller than the proximal phalanx component of FIG. 3A but is similar in other respects. The middle phalanx component will have an endosseous stem 130 and a base 128 . The stem can be either cylindrical, non-cylindrical or a combination of the two, just as its counterpart in FIG. 3A . The stem illustrated in FIG. 3B has a non-cylindrical, oval shape 130 .
The middle phalanx component, like its proximal phalanx counterpart, can have additional structures that inhibit (or prevent) the device from rotating or otherwise loosening after it is inserted into the end of the bone.
When the two components are brought together in correct alignment, a locking mechanism will engage and hold the components together. A preferred locking mechanism features lateral detent arms on one component and a corresponding aperture on the other component. As the two components are slid together the arms are spring loaded then, when they encounter apertures on the corresponding component, the arms spring out and lock the two components together. An example of this preferred locking mechanism is seen in FIGS. 4 , 5 A and 5 B, which are cross-sections of FIGS. 2 , 3 A and 3 B respectively. FIG. 5B illustrates detent arms 132 which have a bulge at the head 134 . The arms are designed so that they can be compressed into an opening 122 ( FIG. 3A ) in the complementary component. Then the arms will spring out when the bulge 134 lines up with the mating aperture 122 in the complementary component. The two components locked together can be seen in FIG. 2 and FIG. 4 which is a cross-section of FIG. 2 taken along line 4 .
The locking mechanism can have an additional design function which allows the two components to properly align and maintain a proper alignment. This is illustrated in FIGS. 6 , 7 A and 7 B, which are cross-sections of FIGS. 2 , 3 A and 3 B taken along line 6 , 7 a and 7 B, respectively. The arms have a taper 132 as shown in FIG. 7B that is sized to completely fill a complementary taper on said parallel inner surfaces 124 shown in FIG. 7A . The taper insures proper alignment and prevents rotation of the components after the components are locked together as shown in FIG. 6 .
Other structures and mechanical components in addition to the one illustrated here can perform the function of locking the two components together. These can be differently shaped prongs, flexible links or any other type of arm or protrusion that extends from one component to the other. The structures can be any male/female pair of mating structure that, when the pairs contact each other, lock the two components together.
Alternatively, the structure used to lock the components together can be extra elements such as various epoxies, adhesives, magnets or the addition of a third structure specifically designed for locking, such as a clip. This third structure would be moved into position and interact with structures on both pieces and keep them together. Of course any common locking mechanism will function with this device such as screws, pins, rivets, nuts and bolts and the like. A preferred locking structure is a detent arm/aperture mechanism.
Under certain conditions it may become desirable to remove the implant or merely separate the two components after they have been joined. For this purpose a separation notch 119 / 129 is provided as shown in FIG. 2 . The notch is shown in the separated components 119 , 129 in FIGS. 3A and 3B . The surgeon can insert into the notch a surgical tool that creates leverage and mechanical advantage allowing the surgeon to pry apart the two components.
The purpose of the implants is to treat bones in an abnormal and sometimes dysfunctional position, such as a hammer toe, and to reestablish function. The bones must function properly throughout active motion of the foot as well as when the foot is at rest. To a first approximation, the functional position is to straighten the PIPJ joint, that is, the longitudinal axis of the proximal phalanx is in axial alignment with the longitudinal axis of the middle phalanx. This may not, in practice, be the optimal position for the PIPJ joint. In another preferred embodiment, a slight angle between these bones may be more functional for a patient. In this case the implants can be altered so that the PIPJ varies from straight to 15° from linear. A preferable angle is 10° from linear. These embodiments are illustrated in FIGS. 8 through 11 . FIGS. 8 and 9 illustrate a device designed to produce a perfectly straight (0° angle) PIPJ joint. FIG. 8 is a top view of the device. FIG. 9 is a side view. Compare these to FIGS. 10 and 11 , which illustrate a device in which the PIPJ joint will be offset from perfectly straight by the angle “θ” which, in this example, is 10°. FIG. 10 is a top view and FIG. 11 is a side view.
Notice that the middle phalanx component 218 in FIG. 11 is offset from the proximal phalanx component 210 , 212 by a distance of “A.” This offset is provided to deal with an issue arising from cannulation of the device. When the device is straight, that is, designed to generate a 0° angle for the PIPJ joint, a cannulation will pass straight down the central axis of both components of the device. The cannulation will enter at the proximal end of the proximal phalanx component and exit out the distal end of the middle phalanx component. When, however, the device is angled a cannulation entering at the proximal end of the proximal phalanx component may exit out the side of the middle phalanx component, rather than the end.
This problem is resolved as shown in FIG. 11 . An offset will allow the cannulation to continue straight through the middle phalanx component and exit out the end. In FIG. 11 the central longitudinal axis of the proximal phalanx component is shown. Note that this axis is extended down the length of the middle phalanx component 218 and exits through the end of the middle phalanx component. This is because the middle phalanx component is offset dorsally (in FIG. 11 this is to the left) by the distance “A.” If the middle phalanx component were not dorsally offset, the central axis line would exit on the dorsal (left) side of the middle phalanx component rather than out the end, as shown. Thus, this offset allows a straight cannulation to pass from one end of the two component device to the other, even if the central axes of the two components are not collinear.
While a preferred embodiment of the device is use in the PIPJ to correct hammer toe, the device is not limited solely to use with the lesser toes but can also be used in fingers as well as the thumb and great toe. Indeed, variations of the device can treat a wide variety of maladies related to improper bone alignment. A non-exhaustive list of examples includes: flexible and rigid hammer toe, deviated/crooked toes or fingers (caused by either physical injury or inherited) arthritic joints, claw toe, mallet toe and long toes requiring shortening (e.g. Morton's Toe).
A preferred material for the implant is medical grade titanium. However, other medical grade materials can also be used.
Method of Treatment for Abnormal Flexion
As discussed previously, hammer toe malady consists of a combination of dorsifexion of the metatarsal/proximal phalangeal joint 108 ( FIG. 1 ) and plantar flexion of the PIPJ 110 ( FIGS. 1 , 12 A). It is treated by correcting the PIPJ 110 misalignment, as illustrated in FIG. 1 and FIGS. 12A-12E . FIGS. 12A-E illustrate the bones flanking the PIPJ in isolation. This series of figures outline a preferred method of use of the interphalangeal joint implant in which the PIPJ 110 is targeted for correction. In a typical operation, an excision is made to expose an area surrounding the PIPJ 110 , the distal end of proximal phalanx 102 and the proximal end of the middle phalanx 104 . These bones are then separated, as shown in FIG. 12B , and the articular cartilage on either side of the joint is removed. If the ends of the bones 300 , 304 are malformed or damaged the ends of the bones may be osteotomized to create a proper surface for the next step in the procedure as shown in FIG. 12C .
Next, central shafts 302 , 306 are introduced into the ends of the bones using standard methods. For example, the ends of the two bones can be “cored” using a trephine, a cylindrical drill with a hollow center. The specifics of the operation are surgeon's choice. For example, to prevent problematic “drift” of the trephine as the teeth first contact the bone, a pilot hole can be drilled first. A trephine with a central drill guide is used as drill guide is inserted into the pilot hole. As long as the drill guide remains in the guide hole, the trephine will remain centered at the proper location during the drilling operation.
After the ends of the bones 300 , 304 are cored to form a central channel to the desired depth 302 , 306 the two components of the implants 112 , 126 are inserted into the bones as shown in FIG. 12D . A proximal phalanx component 112 is designed for insertion into the distal end 300 of the proximal phalanx 102 and a middle phalanx component 126 is designed for insertion into the proximal end 304 of the middle phalanx 104 .
The surgeon should drill the channels so that they form a tight fit with the inserts. If there is any doubt the surgeon should err on the side of drilling a channel that is slightly too large. After insertion, tissue ingrowth can, so some extent, fill in and replace the missing bone tissue to produce a lasting phalangeal joint connection.
The distal interphalangeal joint (DIPJ) 111 , the joint between the middle phalanx and the distal phalanx, can also be affected by bone misalignment and require stabilization. In this case Kirschner wire (k-wire) is employed. K-wire is directed from within the PIPJ out through the tip of the toe making certain that the proximal end of the wire will not prevent the fastening together of the two implant components. When properly installed, k-wire passes through the center of the implant, the middle phalanx and the distal phalanx. The k-wire typically exits the distal end of the distal phalanx. When installed in this manner, the k-wire in combination with the implant will stabilize the DIPJ 111 as well as the PIPJ 110 .
The method functions by restoring a preferred angle, θ, between the central axis of the proximal phalanx and the central axis of the middle phalanx. The angle θ is defined as the degree by which the imaginary central axis of the middle phalanx stem is pointed downward with respect to the imaginary central axis of the proximal phalanx. In one preferred embodiment θ is zero, that is, the two bones are aligned linearly. In another embodiment θ can be any angle between zero and approximately fifteen degrees. In a preferred embodiment θ is approximately ten degrees.
The preferred angles above will be achieved by designing the interphalangeal joint implant so that these same angles are present between the corresponding parts of the implant. The imaginary central axises of the middle phalanx stem and that of the proximal phalanx stem will form the angle θ.
In the specification and claims the expression “approximately” or “generally” are intended to mean at or near, and not exactly, such that the exact location or configuration is not considered critical unless specifically stated.
In the claims in some instances reference has been made to use of the term “means” followed by a statement of function. When that convention is used applicant intends the means to include the specific structural components recited in the specification, including the drawings, and in addition other structures and components that will be recognized by those of skill in the art as equivalent structures for performing the recited function and not merely structural equivalents of the structures as specifically shown and described in the drawings and written specification. The term “attachment” is intended to mean the physical structure disclosed in the specification and also other designs to perform a permanent or reversible connection function such as for example surgical cement, screws, clips, detents, and other attachment structures.
In describing the invention, reference has been made to preferred embodiments. Those skilled in the art however, and familiar with the disclosure of the subject invention, may recognize additions, deletions, substitutions, modifications and/or other changes which will fall within the scope of the invention as defined in the following claims. | A method and apparatus for correcting malformed joints, in particular the “hammer toe” contraction of the proximal interphalangeal joint. The disclosure comprises a two-component implant: a proximal phalanx component and a middle phalanx component. An endosseous stem on each component is inserted axially into the end of a respective host bone and, after insertion, the components are attached. The attached components are held together in various ways, for example a detent arm/aperture mechanism. Each component can be cannulated to allow for the passage of a kirschner wire, if necessary, to stabilize adjacent joints such as the proximal interphalangeal joint. The bones of the treated joint can be set to form a desired angle by adjusting the angle formed by the corresponding endosseous stems. | 0 |
FIELD OF THE INVENTION
The present invention generally relates to packaging apparatus and methods and, more particularly, to shrink wrapping apparatus and methods in which a plastic film shrinks tightly around one or more products.
BACKGROUND OF THE INVENTION
Various methods and apparatus have been employed to shrink a plastic film about one or more products during an assembly line packaging operation. The products may be in many different forms and package configurations. Most notably, these apparatus typically comprise forced air ovens or other tunnel structures through which a conveyor passes. The products, which are encased in a loose plastic shrink film and then placed on the conveyor, pass through the oven or tunnel structure. As they are heated, for example, by a forced air system or other types of heaters, the film shrinks tightly about the product or products. The timing is such that the shrink process occurs as the product or products are traveling from the entrance to the exit of the oven or tunnel.
Ideally, the shrink wrap will uniformly shrink about the outer surface of the product or products with minimal distortion of the film. However, this is especially difficult with products that have irregular shapes. With such products, the shrink film may contact certain areas of the outer surface of the product and may not contact other areas of the outer surface. The problem is further complicated by the fact that many ovens and tunnels have “hot spots” and “cold spots” due to uneven heat distribution within the oven or tunnel interior. For example, ovens that use forced air typically introduce the air into the oven interior through a duct and use various baffles which may be adjustable in an attempt to uniformly distribute the heated air throughout the interior of the oven. This adjustment procedure is often more of an art than a science and, especially when faced with small production runs, the adjustment process becomes even more difficult, inefficient, time consuming and therefore costly. Adjustments must properly balance the temperature, conveyor speed, and air flow through the various ducts and baffle structure. Often, this adjustment process can take up to several hours before achieving consistent shrink wrapped products of a quality acceptable to the customer. As mentioned above, this time consumption is especially impractical and costly for small production runs.
One specific aspect of prior ovens or tunnels which presents certain problems is the riser bar used to raise a short section of the conveyor within the oven or tunnel. These riser bars are used to briefly lift each product during its travel through the oven or tunnel as an aid to more uniformly distribute and control the bubble or balloon-like effect that briefly occurs in the shrink film during the shrink wrap process. As the product is briefly lifted off the conveyor at the riser bar location, the weight of the product is taken off the underlying shrink film. This reduces or eliminates grid marks in the film otherwise caused by the conveyor. Prior riser bars suffer from two general drawbacks. First, the conveyor rubs over the riser bar and, eventually, the friction wears down the riser bar making it less useful and in need of replacement. Second, the riser bar is of fixed diameter and, therefore, may work effectively only across a limited variety of product sizes and configurations run through the tunnel.
To address these concerns as well as other concerns in the shrink wrap field, it would be desirable to provide a shrink tunnel requiring little or no adjustments to be made to achieve high quality shrink wrapping of a wide range of product configurations and sizes. It would also be desirable to provide a shrink tunnel having an adjustable riser member allowing the elevation of a section of the conveyor to be changed in accordance with different product configurations, sizes and weights.
SUMMARY OF THE INVENTION
Generally, the invention relates to an apparatus for shrink wrapping at least one product and including a housing having an interior space with a top, a bottom, an entrance and an exit. The product may or may not be included in another container or package during the shrink wrap process. A heater is thermally coupled to the interior space and a first air mover can be operatively coupled with the interior space and configured to move air generally around the interior space and through the open area of the conveyor belt. A conveyor belt passes through the interior space from the entrance to the exit and preferably comprises an open configuration, such as a mesh configuration.
In one main aspect of the invention, an adjustable riser member is coupled to the conveyor belt and is adjustable in height to raise and lower a transverse section of the conveyor belt. For example, the transverse section of the conveyor belt may be raised higher for larger and/or heavier products and may be raised to a lesser extent for smaller and/or lighter products. For very lightweight products or products which are more prone to tip over, the riser member may be adjusted so that the conveyor remains flat. In the preferred embodiment, the riser member is a bar or shaft extending transverse to the conveyor belt, and optionally including at least one roller engaging the conveyor belt. As another desirable feature, the riser member is adjustable from outside the housing for ease of use by the operator. The conveyor belt is preferably a free tension belt, i.e., one that is mounted and moves under little or no tension. This ensures that the belt height may be easily adjusted without placing the conveyor belt or the riser member under undesirable stress. It will be appreciated that this feature may be incorporated into any type of shrink wrap apparatus.
The openly configured conveyor belt is substantially unobstructed on upper and lower sides thereof as it travels within the housing. For example, the conveyor belt may be supported by the riser member or bar extending across one generally central section thereof transverse to the conveyor path and may also be supported by thin underlying rods.
In accordance with the preferred embodiment, respective upper and lower heaters are located above and below the conveyor belt and are constructed generally as assemblies with the air movers which may comprise fan blades. In another aspect of the invention, the fan blades have at least substantially no pitch. For that reason, the fans do not forcefully direct air at the products moving along the conveyor belt but rather move the air generally uniformly and with relatively low velocity within the interior space of the tunnel. This helps to ensure that no “hot spots” or “cold spots” are created within the interior space of the tunnel.
In accordance with another aspect of the invention, the conveyor belt is positioned closer to a mid-point between the upper heater and the lower heater than to the upper and lower heaters themselves. Due to this generally central positioning of the conveyor belt between the upper and lower heaters, the products moving along the conveyor belt are more uniformly heated on their upper and lower sides. The same spatial relationship also preferably exists between the top and bottom walls of the tunnel housing and the conveyor. This general aspect of the invention furthers the goal of shrinking the plastic film about the product or products without burning the film or producing unacceptable distortions of the film.
The present invention further contemplates various methods of shrink wrapping at least one product including the various operations of the tunnel described hereinabove either taken alone or in any of their various combinations in accordance with the needs of the user.
These and other features, objects and advantages will become more readily apparent to those of ordinary skill in the art upon review of the following detailed description taken in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a shrink tunnel constructed in accordance with the preferred embodiment of the invention.
FIG. 2 is a cross sectional view taken along line 2 — 2 of FIG. 1 .
FIG. 3 is an enlarged view of a portion of the cross section shown in FIG. 2, and illustrating two different positions of the adjustable riser member.
FIG. 4 is an exploded perspective view of one of the air mover and heater assemblies.
DETAILED DESCRIPTION
FIGS. 1-4 illustrate one preferred embodiment of the invention, including its several aspects. As shown generally in FIG. 1, shrink tunnel 10 includes an insulated housing or chamber 12 . As shown further in FIG. 2, insulated housing 12 more specifically comprises end walls 12 a , 12 b and top and bottom walls 12 c , 12 d . Likewise, side walls 12 e , 12 f are thermally insulated, although these walls are not shown in cross section. Each of the walls 12 a-f are preferably formed by an insulating material sandwiched between sheet metal layers. As further shown in FIGS. 1 and 2 shrink tunnel 10 is supported by a frame structure 14 which may ride on lockable caster wheels 16 . A control box 18 is provided for housing heating and motor controls of shrink tunnel 10 . Such controls are conventional and well known to those of ordinary skill and therefore are not detailed herein. A control panel 20 is provided for the operator controls.
A conveyor belt 30 is provided and is preferably constructed with an open mesh-like construction. More specifically, conveyor belt 30 is preferably formed such that it provides at least 80% open area to allow heated air to pass through during the shrink wrap operation. Housing 12 includes an entrance opening 32 and an exit opening 34 (best shown in FIG. 2 ). The entrance and exit openings 32 , 34 are obstructed by high temperature flexible covers or flaps 36 a , 36 b which are slitted to allow for products (not shown) to easily pass through. Covers or flaps 36 a , 36 b help retain the heated air within the interior of housing 12 . A centrally located window 38 is provided above the control panel 20 to allow an operator to observe the products as they pass through tunnel 10 during the shrink wrap process. A second window 40 may also be provided on the opposite side of housing 12 .
More specifically referring to FIG. 2, housing 12 includes an interior 42 having a top 44 and a bottom 46 . Conveyor 30 passes through interior 42 at a height “C” which is closer to the mid-point “M” of the total interior height “H” than to either the top 44 or bottom 46 of interior 42 . This has been found to provide more even heating of products traveling through interior 42 on conveyor belt 30 in the present configuration due especially to the more centralized location of the products relative to the various heaters to be discussed below. As further shown in FIG. 2, various additional frame members, such as frame members 14 , 54 , 56 secure the end walls 12 a , 12 b and top wall 12 c together. A top cover 52 is provided as well.
Referring most particularly to FIGS. 3 and 4, preferably four identical air moving units 60 a , 60 b , 60 c , 60 d are provided with two units 60 c , 60 d located closely adjacent top wall 12 c and two units 60 a , 60 b located closely adjacent bottom wall 12 d as shown in FIG. 2 . Lower air moving units 60 a , 60 b move air generally in an upward direction through conveyor 30 and upper air moving units 60 c , 60 d move air generally downwardly toward conveyor 30 .
Each air moving unit 60 a-d is identical and, therefore only one air moving unit 60 a will be described in detail. As shown in FIGS. 3 and 4 , air moving unit 60 a includes an electric motor 62 secured to bottom wall 12 d with a mounting bracket 64 . Electric motor 62 includes a rotatable output 66 through which it rotates a fan 68 preferably in a range of 500 to 1500 rpm for most applications. Located immediately adjacent to fan 68 , i.e., on the side facing conveyor belt 30 , is an electric heating coil 70 coupled with a conventional heating control unit 72 . Operating together, heating coils 70 maintain a temperature of about 200° F. to 400° F. within interior 42 . As shown in FIG. 2, each electric heating coil 70 may include a cover 74 which is open along its side facing conveyor 30 such that the heat radiating from each coil 70 is essentially radiated toward conveyor 30 . As with the top 44 and bottom 46 of interior 42 , the upper and lower heaters 70 are positioned so that the conveyor belt 30 is closer to midpoint “M” than to either the upper heaters 70 or the lower heaters 70 . As best shown in FIG. 4, fan 68 includes a plurality of radially extending fan blades 68 a . Fan blades 68 a are preferably flat and contained within vertical planes which extend radially from the axis of rotation of fan 68 . In this manner, fan blades 68 have at least substantially no pitch. This ensures that fans 68 gently move the air within chamber interior 42 as opposed to forcefully directing the air in an upward or downward direction. This has been found to provide for “softer” convection characteristics and improved uniformity of temperature, i.e., the elimination of hot and cold spots within chamber interior 42 .
FIG. 2 also illustrates the drive system for conveyor belt 30 generally comprised of a conventional motor and gear assembly 80 which drives one or more sprockets 82 a which are toothed to engage conveyor belt 30 . Preferably, conveyor belt 30 moves at a speed of about 10 ft./min. to 120 ft./min. for most applications. Sprockets 82 a and any additionally necessary circular supports 82 b , as shown in FIG. 1, are fixed for rotation with a shaft 84 which is operatively coupled to motor and gear assembly 80 for rotation by same. This coupling may, for example, be through a belt drive or chain drive, or the output of motor and gear assembly 80 may be directly coupled with shaft 84 . In addition, any suitable drive system may be used other than a motor and gear drive assembly. In one advantageous aspect of the invention, conveyor belt 30 is a free tension belt which is under little or no tension during use. That is, conveyor belt 30 hangs freely from sprockets 82 a and rotating supports 82 b (FIG. 1 ). Thus, as discussed below, a riser bar assembly 90 may be used to raise and lower belt 30 within chamber interior 42 without generating undesirable forces and stress on belt 30 or on the riser bar assembly 90 .
Adjustable riser bar assembly 90 is used to raise and lower a desired transverse section of conveyor belt 30 within chamber or housing interior 42 as shown in FIGS. 2 and 3. Raising and lowering a transverse section of belt 30 helps to ensure higher quality shrink wrapping of packages and/or product containers, and the height adjustability provided by this invention allows a wider range of package and product container sizes and configurations to be shrink wrapped in the same tunnel with more uniform, higher quality results. As best shown in FIG. 3, riser bar assembly 90 specifically comprises a pivoting support 92 which rotates from the position shown in solid lines to the position shown in dashed lines about a pivot rod 94 . Pivot rod 94 is supported for rotation in a slot 96 a of a stationary support plate 96 . Stationary support plate 96 includes an additional slot 96 b which may be used when conveyor belt 30 is moving in the opposite direction. Although not shown, there is a similar pivot and support assembly on the opposite side of conveyor belt 30 .
A riser bar actuating rod 98 is coupled to a link 100 by a pivot 102 . Link 100 is further coupled to pivoting support 92 by a second pivot 104 . At least one roller or bearing 106 is coupled to a shaft (not shown) which is coupled to and coaxial with pivot 104 . Multiple rollers 106 may be provided at spaced locations across the width of conveyor belt 30 for supporting belt 30 while providing as little obstruction to the flow of air at that location as possible. One or more rollers 106 provide reduced friction as conveyor belt 30 passes over them and briefly elevates. At this location, a product (not shown) which is encased in a shrink wrap film is also briefly elevated such that the bubble which is created by the heated shrink wrap film during the shrink wrap process is more uniformly distributed about the product or its particular package configuration. This helps ensure that the shrink wrap film itself is more evenly heated and therefore subject to less distortion and more uniform shrinking of the shrink film.
Adjustable riser bar assembly 90 allows a transverse section of the conveyor belt 30 to be elevated to different heights within a predetermined range by moving actuating rod 98 back and forth in the direction of arrow 110 as shown in FIG. 3 . To accommodate most applications, the height adjustment may be in the range of 0 to 1½”. When moved to the right, actuating rod 98 rotates pivot support 92 in the direction of arrow 112 to the position shown in dashed lines. Thus, the two extreme positions are shown in FIG. 3 with the solid line depiction of support 92 and roller 106 illustrating the highest elevation of conveyor belt 30 and the dashed line depiction showing roller or rollers 106 completely disengaged from conveyor belt 30 . Higher elevations tend to be useful for shorter, heavier products. In the disengaged position of roller 106 , conveyor belt 30 is maintained completely planar during its travel through interior 42 . This position is useful, for example, when the products are prone to tip during elevation by the riser bar, or for very lightweight products which will be elevated by the shrink film bubble formed during the process and, therefore, do not need to be elevated by any additional structure. Preferably, actuating rod 98 extends to the exterior of housing 12 such that it may be operated to raise and lower conveyor belt 30 without the necessity of the operator reaching into chamber interior 42 . Actuating rod 98 is secured in the desired position, thereby securing the height of conveyor belt 30 at the desired elevation, by a suitable retaining assembly also located outside of interior 42 , such as a clamping structure (not shown). It will be appreciated that such a retaining assembly or device would simply prevent any further linear motion of actuating rod 98 in opposite directions indicated by arrow 110 (FIG. 3 ).
While the present invention has been illustrated by the description of various embodiments thereof, and while the embodiments have been described in considerable detail, it is not intended to restrict or in any way limit the scope of the appended claims to such detail. Additional advantages and modifications will readily appear to those skilled in the art. The invention in its broader aspects is therefore not limited to the specific details, representative apparatus and methods and illustrative examples shown and described. Accordingly, departures may be made from such details without departing from the scope or spirit of applicants' general inventive concept. | A tunnel for shrink wrapping at least one product includes a housing having an interior space with a top, a bottom, an entrance and an exit. A conveyor belt passes through the interior space from the entrance to the exit. The conveyor belt is substantially unobstructed on upper and lower sides and includes an opened configuration allowing substantial air flow therethrough at relatively low velocity. Heaters and air movers are located above and below the conveyor belt to uniformly heat products contained in shrink film and moving along the conveyor belt. The shrink tunnel further includes an adjustable riser member to allow a transverse section of the conveyor belt to be selectively adjusted in height from outside the housing. | 1 |
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates generally to moving objects and devices for use therewith, and more particularly, to methods and devices for accelerating and decelerating moving vehicles.
[0003] 2. Prior Art
[0004] Along many highways, exits are provided for runaway trucks or other types of vehicles. Once a vehicle takes such an exit, it enters a stretch of a road that is filled with relatively fine sand of an appropriate depth. As the runaway vehicle enters the sand-filled portion of the road, it quickly begins to decelerate and slow down and after a relatively short distance it comes to rest. The deceleration of the vehicle is caused primarily by the process of “sinking” the vehicle tires into the sand, and forcing it to continuously “climb the height of the sand in front of it, i.e., a height equal to the sinking depth of the tire. The kinetic energy of the vehicle is absorbed primarily by the friction forces generated within the displacing sand. This process is fairly similar to an uphill travel of a vehicle, which would decelerate a non-powered vehicle and eventually bring it to rest. The amount of deceleration, i.e., the rate of slow-down, is dependent on the uphill slope. For the case of a sand-filled road, the amount of deceleration that can be achieved is dependent on the depth of the sand and the mechanical characteristics in terms of the amount of resistance that it can provide to its displacement by the tires.
[0005] As the vehicle travels along the sand-filled road, the vehicle usually experiences a fairly bumpy ride, since the sand cannot be made and maintained perfectly flat and perfectly homogeneous or protected from contaminants carried by the wind and rain and also by an uneven absorption of moisture. Another major disadvantage of the sand is that due to the relatively small friction that it provides between the tire and the roadway, the tires can easily skid sideways and slip, particularly if the driver attempts to use the brakes, and the vehicle may easily be rendered minimally controllable while slowing down. As a result, accidents, such as overturning and jackknifing, can occur while the vehicle is being brought to rest. The skidding, slipping and partial loss of control becomes increasingly more probable with increased initial speed of the vehicle as it enters the stretch of sand-filled road.
[0006] In addition, a depth of sand that is most appropriate for a certain vehicle weight, number of tires, and/or tire size may not be appropriate for other vehicles having a significantly different weight, number of tires, and/or tire size. For example, a road with a depth of sand that is appropriate for a heavy truck will decelerate a light vehicle too fast and can therefore result in injury to the passengers due to the rapid deceleration and/or most likely due to the vehicle loss of control. The optimal depth of the sand is also dependent on the initial speed of the vehicle. If a vehicle enters the sand-filled road with a relatively slow speed, then it would be best for the depth of sand to be relatively small, so that the vehicle is brought to stop as slowly as the length of the sand-filled road allows. Other factors also contribute to the optimal design of such sand-filled roads such as the weight of the vehicle, the number and size of the tires, etc. In short, to achieve an optimal condition, a sand-filled road has to be tuned to the type of the vehicle, its entering weight and initial velocity. In addition, the road and sand conditions have to be regularly monitored and maintained. Such conditions cannot obviously be met for roads that are constructed for general use and are subject to various environmental conditions. Such sand-filled roads are in use in numerous highways and are particularly located where the downward slope of the road is high and heavier vehicles such as trucks are prone to run away and are used as the means of last resort.
[0007] Such sand-filled roads are not, however, suitable for fast moving vehicles such as airplanes. For the case of airplanes, other issues may also arise. For example, the load on each tire is usually much larger than road vehicles; the relative distance between the tires may be smaller than those of road vehicles, thereby rendering them more uncontrollable; the center of mass of the plane may be higher than that of road vehicles, thereby making them more prone to tipping over; etc. In addition, and particularly for fast moving planes, the load applied to the tires keep varying due to the suspensions and the lift action, and therefore may cause a ripple to be formed on the surface of the sand-filled road, thereby making the ride even more bumpy and uncontrollable. In addition, the sand-filled section of the runway needs to be re-leveled after each use. In short, sand-filled roads are not appropriate and practical for fast moving vehicles in general and for airplanes in particular.
[0008] To overcome the aforementioned shortcomings for airplanes, runway segments have been added to the end of test runways that are constructed with a special type of concrete that collapses in a more or less controlled manner under the load of the airplane tire. Such runway segments solve some of the aforementioned problems of sand-filled roadways. However, such runway segments leave some of the major aforementioned problems unsolved and they even create some new problems and hazards. For example, the problem of lack of control is only partially solved by reducing the skidding potential caused by the sand. However, the collapsed concrete tends to constrain the tire to travel, more or less, in the generated “groove,” making it difficult for the plane to maneuver (turn) sideways due to the resistance that the uncrushed “concrete wall” provides against the tire as it attempts to turn sideways. In addition, the concrete material cannot be formed such that it is sufficiently homogeneous to prevent bumpy rides. In addition, the collapsible concrete runway can only be optimally formulated and constructed for a certain airplane with a certain total weight and certain initial velocity as it reaches the collapsible segment of the runway.
[0009] Furthermore, once the collapsible segment of the runway is used by a “runaway” plane during landing or takeoff, the damaged segment has to be repaired before the runway can be opened to traffic. Otherwise, the damaged segment would pose a hazardous condition for the next runaway plane or even for a plane that could have stopped if a regular runway segment was present in place of the collapsible segment. In addition, while the repair crew is repairing the damage, any takeoff or landing would pose a hazardous condition for the repair crew and the plane. The use of the runway must therefore wait for the completion of the repairs, including the time required for the proper setting of the added or replaced sections of the concrete and inspection of the final condition of the runway. In short, the operation of the airport must be significantly curtailed for a significant length of time, and if the airport has only one runway, the entire operation of the airport has to be suspended until the damaged sections of the collapsible runway has been repaired. In short, such collapsible runway segments have major technical difficulties for safe operation and even those technical problems are one day solved, they are still effectively impractical due to the required relatively long periods of closure after each use and the related economical costs involved.
[0010] A need therefore exits for reusable runways and driveways that can slow down or bring to stop a “runaway” vehicle. For high-speed approaches, particularly for airplanes, it is also essential that the ride be as smooth as possible and that the vehicle stays fully controllable during the entire time it is being decelerated. It is also highly desirable that the runway or driveway parameters be readily adjustable to optimally match the type, weight and initial speed of the vehicle. Such adaptable runway segments are particularly important for planes for the aforementioned reasons and in practice, the parameters of the runway segment can be readily adjusted by the air traffic controller or even by the pilot since all the required information about the plane and its flight conditions is known prior to landing and takeoff. The information may even be automatically transmitted from the plane by a wireless means to a central processor. In addition, if the plane is experiencing some type of malfunction or is damaged, the runway segment may be adjusted for optimal performance with each specific condition. Such changes in the runway parameters may be achieved manually or automatically before the plane reaches the runway segment or even as it is traveling along the runway.
[0011] Such runway segments may even be placed along the entire length or a portion of the runway (or other road surface) to routinely assist in the deceleration of aircraft (or other vehicles), thereby reducing their tire and brake wear. The equipped runway segments may also be kept inactive, thereby acting as a regular (solid) segment of the roadway surface, and be activated only when needed, such as in an emergency.
SUMMARY OF THE INVENTION
[0012] Hereinafter, such runway or driveway segments are referred to as “reusable and adaptive runways” (RAR) without intending to limit their applications to airplanes or for their deceleration. Those skilled in the art will appreciate that the devices and methods of the present invention, although having particular utility for decelerating aircraft, can be used for any type of vehicle and for deceleration as well as acceleration thereof. For example, the RAR can be used on portions of a highway, such as on segments of the shoulders of the roadway for emergency stops or on exit ramps to assist in decelerating vehicles, particularly those that are traveling at dangerously high speeds, as they leave the highway. Thus, the RAR can be used regularly in such situations to decrease the length of exit ramps, or can be used in connection with a detection system and only employed where a dangerous condition is detected. In the latter, for example, a detection system can detect a large truck traveling too fast for a particular exit ramp and as a result automatically activate the RAR to slow the truck. Of course, a manual operator can also activate the RAR, which can be the driver of the truck.
[0013] During landing, the kinetic energy of the airplane due to its mass and speed is transformed into potential energy stored in elastic or other similar types of elements of the RAR. A portion of the kinetic energy, preferably a small portion, is transformed into other types of energies such as heat. The stored potential energy may later be used to accelerate the airplane forward during takeoff, thereby reducing the amount of energy required to bring the plane to its takeoff speed, and/or shorten the length of the runway needed for takeoff.
[0014] The primary objective of the present invention is to provide reusable and adaptive runways (RAR) that can be used safely by high-speed vehicles in general and airplanes in particular. To this end, the disclosed RAR has one or more of the following characteristics:
[0015] 1. The RAR is preferably reusable, in the sense that none of its components are permanently damaged after each use and can be brought back to its usable condition within a very short period of time automatically or by an operator.
[0016] 2. An operator is preferably able to set and control the parameters of the runway to optimally match the type, weight, initial speed and other appropriate traveling conditions of the vehicle as possible.
[0017] 3. As the vehicle travels along the RAR and its characteristics and traveling conditions are measured more accurately or is varied, the parameters of the RAR can be preferably adjusted accordingly for more optimal operation of the RAR. For example, if the vehicle brakes are still operational, then the RAR could be set to only assist the brakes in stopping or slowing down the vehicle.
[0018] 4. The runway may preferably be equipped with any one of the available means of determining the entering speed of the vehicle, its weight and by means of a pattern recognition software, the type of vehicle and any visible structural damage for optimally setting the parameters of the RAR automatically or by an operator (which may be the driver or the pilot).
[0019] 5. The runway may be equipped with the communications equipment necessary to receive the information indicated in the previous item directly from the vehicle for use for optimally setting the parameters of the RAR automatically or by an operator (which may be the driver or the pilot). The RAR controller may combine the information received from the vehicle with information collected by the runway sensory instrumentation (as described in the previous item) to check for any discrepancy or added information and base its decision for optimal setting of the RAR parameters on the total collected data for maximum reliability.
[0020] 6. The RAR provides a safe process for slowing down the vehicle or for bringing it to a stop in the sense that it does not reduce the friction between the tire and the runway surface and it does not tend to force the tire to follow a given path such as the impressed path generated in the collapsible concrete or sand, both of which can readily lead to skidding, slippage and/or loss of control by the pilot or driver.
[0021] 7. The operator of the vehicle or the runway or an appropriately computerized automated control unit is preferably able to optimally set the parameters of the RAR for bringing the vehicle to a complete stop or to a reduced speed over a desired distance of travel along the RAR.
[0022] 8. The RAR system can be set to operate automatically, i.e., become operational for each and every landing and takeoff, thereby providing a failsafe mechanism for the operation of runways.
[0023] 9. The entire or a major segment of the runway may be constructed as a RAR unit, thereby allowing planes to use them to bring them to a stop with minimal or less use of their brakes, thereby minimizing braking system, tire, and runway wear.
[0024] Another objective of the present invention is to provide the means to reduce the required length of runways for landing airplanes, while reducing stress on the structure of the airplane during hard braking, reducing tire wear, reducing brake wear, and making the airplane more controllable during its deceleration. Deceleration by braking is the result of the work done by the friction force between the tire and the road surface. This friction force tends to tip over the vehicle since it acts at a point away (below) the center of mass of the vehicle. In this regard, an advantage of the RAR runways is that it can decelerate vehicles without the tendency of tipping them over.
[0025] Another objective of the present invention is to provide the means to reduce the required length of runways for airplane takeoff, while reducing the stress on the structure of the plane and saving fuel.
[0026] Another objective of the present invention is to provide RAR segments that partially disabled airplanes may use for landing with greatly increased probability of coming to stop safely rather than, e.g., sliding uncontrollably to a stop over great distances, which could mean leaving the runway and striking some obstacles or falling into a ditch or water. In addition, since the runway surface is readily accessible from under the RAR surface panels, provisions can be made to introduce highly sticky and/or fire retardant or fire distinguishing substances such as fluid or foam to the surface of the runway or spray the same some distance above the surface over the incoming vehicle to significantly reduce the probability of fire and/or introduce fire inhibiting gases so that the spilled fuel could not be ignited and/or prevent the fire from spreading.
[0027] In the remainder of this description, the basic principles of operation and various embodiments of the present invention are described in terms of airplanes and runways. However, it is understood that whenever applicable, the terms also apply to ground and other similar vehicles.
[0028] A basic principle of the operation of the reusable and adaptable runaways (RAR) of the present invention is the provision for the vehicle (tires or some other structural member of a damaged aircraft) to continuously tend to climb an inclined surface, which under the weight of the vehicle undergoes a displacement thereby deforming certain elastic elements. The process is similar to the vehicle traveling uphill, and as the vehicle travels along the runway, its kinetic energy is stored in the deformed elastic elements. However, no significant amount of potential energy stored in the elastic elements is preferably transferred back to the vehicle as it passes over the displaced surface of the RAR. To this end, appropriate means are preferably provided to “lock” the elastic elements in their deformed position, i.e., to “lock” the runway structure and its various members substantially in their deformed configuration.
[0029] Accordingly, a roadway upon which a vehicle travels is provided which assists in decelerating the vehicle. The roadway comprises: a movable surface extending in a direction of the vehicle's travel; and potential energy storage means operatively connected to the movable surface for converting a kinetic energy of the vehicle into potential energy upon movement of the movable surface thereby slowing the vehicle.
[0030] Also provided is a roadway upon which a wheeled vehicle travels which assists in accelerating the vehicle. The roadway comprises: a movable surface extending in a direction of the vehicle's travel; and potential energy transfer means operatively connected to the movable surface for transferring a stored potential energy associated with the movable surface into kinetic energy upon movement of the movable surface thereby propelling the vehicle.
[0031] Still provided is a method for slowing a vehicle upon a roadway. The method comprising: providing a movable surface upon which the vehicle travels; converting a kinetic energy of the vehicle into potential energy upon movement of the vehicle over the movable surface; and storing the potential energy in the elastic elements of the movable surface mechanism to thereby slow the vehicle.
[0032] Still provided is an RAR in which part or all of the kinetic energy transferred to the movable surface mechanism is absorbed by viscous damping and/or dry friction forces and/or by controlling electric motors and/or electric power generators.
[0033] Still yet further provided is a method for accelerating a vehicle upon a roadway. The method comprising: providing a movable surface upon which the vehicle travels; and moving the movable surface to transfer a potential energy stored in the movable surface to the vehicle to thereby propel the vehicle.
BRIEF DESCRIPTION OF THE DRAWINGS
[0034] These and other features, aspects, and advantages of the apparatus and methods of the present invention will become better understood with regard to the following description, appended claims, and accompanying drawings where:
[0035] FIG. 1 illustrates a schematic sectional view of a preferred implementation of a reusable and adaptive runway of the present invention.
[0036] FIG. 2 illustrates a schematic of a single runway panel and support and control elements corresponding to the panel.
[0037] FIG. 3 illustrates a schematic of the single runway panel of FIG. 2 under the weight of a vehicle tire.
[0038] FIG. 4 illustrates a schematic cross section of another preferred implementation of the reusable and adaptive runway of the present invention.
[0039] FIG. 5 illustrates a schematic cross section of yet another preferred implementation of the reusable and adaptive runway of the present invention.
[0040] FIG. 6 illustrates a schematic cross section of still another preferred implementation of the reusable and adaptive runway of the present invention.
[0041] FIG. 7 illustrates a schematic cross section of another implementation of the reusable and adaptive runway of the present invention.
[0042] FIG. 8 illustrates a schematic cross section of still another preferred implementation of the reusable and adaptive runway of the present invention.
[0043] FIG. 9 illustrates a graph showing a preferred relationship between spring displacement and force for the spring elements of the reusable and adaptive runway of the present invention.
[0044] FIG. 10 illustrates a schematic cross section of still another preferred implementation of the reusable and adaptive runway of the present invention.
[0045] FIG. 11 illustrates a schematic cross section of still another preferred implementation of the reusable and adaptive runway of the present invention.
[0046] FIG. 12 illustrates a schematic cross section of still yet another preferred implementation of the reusable and adaptive runway of the present invention.
[0047] FIG. 13 illustrates a sectional view of a vehicle tire having means for converting kinetic energy of the vehicle to potential energy, similar to that of the RAR.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0048] Although this invention is applicable to numerous and various types of roadways and surfaces, it has been found particularly useful in the environment of runways for aircraft. Therefore, without limiting the applicability of the invention to runways for aircraft, the invention will be described in such environment. Those skilled in the art will appreciate that the RAR of the present invention can be used on roadways for automobiles and trucks and for other wheeled vehicles. The RAR of the present invention can also be adapted for use with trains where the panels described below are proximate the rails upon which the trains travel.
[0049] A schematic of the side view of a preferred RAR illustrating its basic principles of operation is shown in FIG. 1 . In this illustration, the RAR 100 segment is shown positioned at the end of a typical (fixed) runway 101 . At the end of the fixed runway 101 , one or more transition runway panels 102 are to be installed in a transition segment 103 of the RAR 100 . The function of the transition segment 103 of the RAR 100 is to provide for a smooth transition for a vehicle during its motion from the fixed segment of the runway 101 to the RAR segment 100 . In general, more than one transition runway panel 102 is preferred in order to make the vehicle motion smooth as it enters the RAR segment 100 of the runway, i.e., in order to prevent the tires from suddenly striking the RAR segment 101 which would otherwise form a step like configuration immediately following the fixed runway segment 100 .
[0050] The transition runway panels 102 are constructed with a surface panel 102 which make an angle α ( 104 in FIG. 1 ) with the surface of the fixed runway 101 , rising to the height H ( 105 in FIG. 1 ). Under the transition runway panel(s) 102 are elastic elements, motion constraining mechanisms, braking mechanisms, and all other components, collectively shown in FIG. 1 as element 106 , which hereinafter is referred to as the runway panel “support and control assembly.” The details of the support and control assembly 106 is provided in FIG. 2 . The support and control assembly 106 is mounted on a runway foundation 107 . Following the transition runway panels 102 , the regular runway panels 108 are positioned. The runway panels 108 are held in place above the foundation 107 by support and control elements 109 , which are very similar in function and construction to the support and control elements 106 . In FIG. 1 and to simplify the illustration, the mechanisms used to attach the transition panels 102 to the fixed runway 101 and to the other transition 102 and regular runway panels 108 are not shown. These details are provided in the ensuing illustrations. In addition, it is understood that the outermost side of the runway panels 108 are preferably not exposed. In practice, the sides of the runway panels 108 are preferably protected from the elements without the addition of any motion restraining elements such as with simple bellows. In addition, it is understood that in FIG. 1 only one runway panel 108 is shown along the width of each segment of the RAR 100 . However, it is understood that more than one runway panel 108 may be positioned side by side along the width of each runway panel segment 108 .
[0051] The structure of the simplest type of support and control elements 106 and 109 is shown in the schematics of FIGS. 2 and 3 . Such a support and control element consists of one or more spring elements 110 and one or more braking elements 111 connecting the runway panels 102 and 108 to the runway foundation 107 . As the vehicle tire 112 leaves the fixed portion of the runway 101 , it first rolls over the panels 102 within the transition segment 103 of the RAR 100 , and then rolls over the regular RAR panels 108 as shown in FIG. 3 . The relatively small angle α ( 104 ) ensures that the transition between the transition panel 102 and regular panel 108 segments of the RAR 100 is relatively smooth. Depending on the weight W ( 114 ) being born on the tire 112 and the total spring rate provided by the spring elements 110 , the panel 102 ( 108 ) is displaced downward a distance D ( 113 ) as shown in FIG. 3 . The spring rate is preferably selected, i.e., set by a spring rate adjustment mechanism (not shown) such that the amount of downward displacement D ( 113 ) is fairly close to the height H ( 105 ) of the regular panels 108 . The amount of potential energy PE stored in the spring elements 110 is readily shown to be
PE= 1/2 k D 2 (1)
where k is the effective spring rate of the spring elements 110 , assuming that the spring elements 110 are not pre-loaded. If the spring elements 110 are pre-loaded a distance D 0 , then the potential energy stored in the spring elements 110 is readily shown to be
PE= 1/2 k ( D+D 0 ) 2 −1/2 k D 0 2 (2)
[0053] In general, the spring elements 110 are desired to be pre-loaded in order to reduce the amount of displacement D for a desired level of potential energy PE.
[0054] The source of potential energy PE that is stored in the spring elements 110 is the kinetic energy of the vehicle. Therefore, the kinetic energy of the vehicle is reduced by the amount of potential energy PE that is stored in the RAR panel 102 ( 108 ). Obviously, the panel 102 ( 108 ) and thereby the spring elements 110 have to be locked in their displaced position shown in FIG. 3 . Otherwise, as the tire 112 passes over the panel 102 ( 108 ), the panel 102 ( 108 ) could transfer most of the stored potential energy back to the tire, thereby causing the RAR system to have a minimal effect in absorbing the kinetic energy of the vehicle, i.e., from slowing the vehicle down. Here, the locking action is intended to be provided by the brake 111 , which is actuated by the braking force 115 .
[0055] The preferred length of each of the RAR panels 102 ( 108 ) relative to the size of the tire 112 and the preferred methods of connecting the panels 102 ( 108 ) together and to the runway foundation 107 will be described later.
[0056] The components shown in the support and control elements 106 and 109 are the minimum type of elements that allow for the proper operation of the RAR 100 . Additional elements, such as those previously mentioned may, however, be added to provide for features that may be desirable depending on the operational requirements of each runway, the level of automation that is desired to be incorporated into the overall design, for allowing for the adjustment of one or more of the parameters of the system, its effective height H ( 105 ), the configuration of the system, etc. In the remainder of this description, various preferred design configurations and the types and ranges of parameters are provided as a function of various desired operating conditions.
[0057] The operation of such reusable and adaptive runways (RAR) 100 is equivalent to the vehicle traveling along an inclined surface, thereby transforming its kinetic energy into potential energy proportional to the vertical height that its center of mass attains. In the present invention, the kinetic energy of the vehicle is transformed into potential energy stored in the deforming elastic elements, i.e., the springs 110 . In certain situations, it may be desired to provide friction (braking action) and/or viscous damping elements that are positioned in parallel or in certain cases in series with the elastic elements, thereby dissipating a certain portion of the kinetic energy of the vehicle. Yet in other certain situations, it may be desired to use kinetic energy storage elements such as flywheels in series or in parallel with the elastic elements or even in place of the elastic elements. In a similar design, opposing magnet or magnets and coils (i.e., linear or rotary motors) may be used in parallel or in series with one or more of the aforementioned elements. Yet in certain other situations, electrical energy generators may be positioned in series or parallel with the elastic elements or in place of the elastic elements, or in series or parallel with the kinetic energy storage elements or in place of the kinetic energy storage elements. The electric energy generators or electric actuation devices (or in fact any other means of actuation) may be used as means to absorb part or the entire kinetic energy that is transferred to the RAR panels, or they may be used in part or entirely as means of controlling the rate of such energy transfers. The latter means of control is usually aimed at achieving a smooth motion for the vehicle. In general, the spring rates, viscous damping rates, and the characteristics of any one of the aforementioned elements may be constant or adjustable. Such means of adjustment of the characteristics and parameters of the aforementioned elements may be used to adjust the characteristics of the RAR 100 to their near optimal conditions for each approaching vehicle, its speed, and operating condition. The aforementioned elements may also have linear or nonlinear characteristics. The advantages and disadvantages of a number of aforementioned combinations and the general characteristics that they can provide the RAR system is described later in this disclosure.
[0058] In short, a number of combinations and configurations of one or more elastic elements, one or more kinetic energy storage elements, one or more viscous damping elements, one or more braking elements, one or more electrical or hydraulic or pneumatic motors or their combination, and one or more electrical energy generators may be positioned in series or in parallel to provide the desired effect of “absorbing” the kinetic energy of the vehicle.
[0059] The RAR panels 102 and 108 are preferably constructed with relatively rigid but lightweight materials as relatively rogod but lightweight structures. The surface of the panels are preferably coated with appropriately formulated material to enhance endurance, increase friction and decrease wear.
[0060] The RAR surface panels 102 ( 108 ) may be constructed with panel or panel like elements that are relatively free to move relative to each other, particularly in the vertical direction and in rotation about a transversely directed axis (perpendicular to the vertical and longitudinal axes of the runway or roadway). In such a configuration, the horizontal motion of the panels 108 relative to each other and relative to the runway foundation 107 is preferably controlled by relatively stiff elastic elements 125 ( FIG. 4 ), preferably with a considerable amount of (preferably viscous like) damping (such as with synthetic rubber type of materials) in order to control the panels from slipping in the longitudinal direction under the rotating tire. Mechanical stops may also be provided to assist in the control of the horizontal motion of the RAR panels 108 . Such a RAR panel configuration is suitable when the size of the panels 108 , particularly their length (measured along the length of the runway) is relatively small compared to the size of the vehicle tire such that at any point in time, the tire is in contact with more than one panel 108 , preferably with at least three panels 108 . The latter condition is necessary in order to assure a smooth motion for the vehicle as the tire moves from one panel 108 to the other, causing the panels 108 to generally conform to the shape of the tire as shown in FIG. 4 , rather than causing the tire to move up a step like path.
[0061] In another embodiment of this invention, the surface panels 102 ( 108 ) are hinged together as shown in FIG. 5 along the length of the runway to allow for their relative rotation about their transverse axes in order to accommodate to the shape of the traveling tire 112 . The panels 108 (or 102 ) are connected with hinges 120 to allow their relative rotation. Such a rotation is required for the smooth operation of the RAR so that as the tire moves over the first panel 108 ( FIG. 5 ) and depresses a certain amount, the next panel 108 is rotated counterclockwise the required amount to allow such vertical displacement of the first panel 108 without resulting in a step to be formed between the two panels 108 . The hinge 120 or at its connections to the panels 108 or the panels 108 themselves may be constructed with certain amount of flexibility to allow the change in the horizontal projection of the longitudinal length of the panels due to the relative rotation of the panels 108 to be compensated.
[0062] In yet another embodiment of the present invention, the panels are attached to the underlying structure (foundation 107 ) of the runway by means of mechanical elements, i.e., linkage or other types of mechanisms, such that their motion relative to the foundation is constrained in certain manner to allow for the smooth travel of the tire over the panels. An example of one of numerous possible types of such motion constraint mechanisms is shown in FIG. 6 . This mechanism is constructed with linkage type of mechanisms. In FIG. 6 , the side view of only one runway panel 108 ( 102 ) is shown. In this design, one side of the panel 108 ( 102 ) is attached with two links 136 and 137 which are hinged together at the hinge 134 . The link 136 is attached to the runway panel 108 ( 102 ) by the hinge 130 . The link 137 is attached to the runway foundation 107 by the hinge 132 . The opposite end of the panel 108 ( 102 ) is attached to the foundation 107 by links 138 and 139 which are hinged together with hinge 135 . In turn, the link 138 is attached to the panel 108 ( 102 ) by hinge 131 and link 139 is attached to the foundation 107 by hinge 133 . The pair of links 136 and 137 and the pair of links 138 and 139 reduce the total degree of freedom of the panel for motion in the vertical plane from three degrees of freedom (two displacements and one rotation) to two degrees of freedom, i.e., the motion of the panel in the vertical plane is constrained by the linkage mechanism shown in FIG. 6 to two degrees of freedom. As a result, other elements of the mechanism 106 ( 109 ) (not shown in FIG. 6 for clarity), mostly the spring elements 110 , provide fewer constraining forces to provide for the aforementioned desired motion of the panels as the tire travels over the panel. Those skilled in the art will appreciate that the elastic elements are operatively connected with the panels (or belt) to convert the kinetic energy of the vehicle to potential energy. Thus, the elastic elements can be directly connected to the panels (or belt) or connected to the links in way which deforms the elastic element(s) upon movement of the links.
[0063] It should be noted that in general, the panels 108 ( 102 ) are desired to possess two degrees of freedom in motion in the vertical plane. This is the case since as the tire travels over the panels 108 (except a panel 102 located immediately following the fixed segment of the runway), the panels 108 are desired to undergo a motion which is essentially a counterclockwise rotation that brings their edge closest to the tire downward, followed by a clockwise rotation that brings the opposite edge of the panel downward until the panel is essentially horizontal. It is readily observed that if the panels 108 are short relative to the size of the tire 112 as shown in FIG. 4 , then during the above counterclockwise and clockwise rotations, the panels 108 would also undergo a vertical displacement such that the panels are essentially tangent to the periphery of the tire 112 at all times. However, panels 108 that are long relative to the size of the tire 112 such that the tire 112 may be located at times entirely over the surface of only one panel 108 , would undergo a more or less pure counterclockwise rotation as the leading edge of the panel 108 closest to the tire 112 is pushed downward to essentially the maximum set depth 105 , and as the tire 112 moves over the panel 108 , the panel 108 would then begin to rotate clockwise about the same leading edge until the panel 108 is essentially horizontal. The configuration of the panels 102 ( 108 ) is shown by way of example only and not to limit the scope or spirit of the present invention. For example, as shown in FIG. 12 , all or a significant portion of the panels can be arranged at an angle α such as the transition panel 102 , or alternatively, all of the panels could be arranged flat (e.g., α=0), such as panels 108 . In the alternative configuration of FIG. 12 , the panels 102 are not attached to each other but are instead all hinged to the roadway for pivotal movement therewith.
[0064] Another class of mechanism that may be used to constrain the motion of the aforementioned longer runway panels 108 ( 102 ) relative to the runway foundation 107 to the aforementioned sequential counterclockwise and clockwise rotation about the leading edge 140 closest to the incoming tire 112 , as shown in FIG. 7 . In this class of constraining mechanisms, the motion of the leading edge 140 of the panel 108 is constrained to a vertical motion, while the panel 108 ( 102 ) is free to rotate about the leading edge 140 . In the mechanism shown in FIG. 7 , the motion of the edge 140 is constrained to the vertical direction by the sliding joint 141 , which consists of the sliding element 143 and the guide 144 . The sliding element 143 is hinged to the edge 140 of the panel 108 ( 102 ) by a rotary joint 142 , thereby allowing the panel to rotate counterclockwise as the edge 140 is pushed down to the previous panel and once the tire 112 begins to move over the panel 108 ( 102 ) shown in FIG. 7 , to allow the panel 108 to rotate in the clockwise direction until it is essentially horizontal and depressed a distance H 105 . A plurality of such motion constraint mechanisms may be constructed. In fact, the mechanism shown in FIG. 7 is selected only for the purpose of demonstrating the mode of operation of such motion constraint mechanisms and does not constitute the preferred embodiment unless the sliding joint is constructed as a living joint. This is the case since sliding joints constructed sliding and guiding elements, even together with balls or rollers or other anti-friction constructions, are much more susceptible to sticking, generally generate more friction forces, are harder to keep free of dirt and contaminants, and are generally larger and heavier, thereby are generally desirable to be avoided. The preferred mechanisms are constructed with rotary joints, such as in the form of one of many well-known linkage mechanisms that generate nearly straight-line motions.
[0065] Motion constraining mechanisms may also be preferably used to constrain the motion of the panels 108 ( 102 ) to rotations about axes perpendicular to the longitudinal and vertical directions, i.e., clockwise and counterclockwise rotations as illustrated in FIGS. 4, 5 , 6 , and 7 . In the schematic of FIG. 8 , the edge 150 of a runway panel 108 ( 102 ) along the width of the runway 107 , i.e., as viewed in a direction parallel to the longitudinal direction of the runway, is illustrated. To limit the motion of the runway panel to the above rotations, the motion constraining mechanism constrains the edge 150 to motions in the vertical direction while keeping the edge 150 parallel to the horizontal plane (here, for the sake of simplicity and without intending to place any limitation on the design of the runway foundation, the foundation surface is considered to be flat and parallel to the horizontal plane). The simplest linkage mechanism that would provide the above constraining motion, is a double parallelogram mechanism 160 as shown in FIG. 8 . The mechanism consists of links 153 of equal lengths that are attached to the runway panel 108 ( 102 ) by spherical joints 151 ; links 155 of equal lengths that are connected to the foundation 107 with spherical joints 156 ; and a common link 154 to which the ends of the links 153 and 155 are hinged with rotary joints 152 . One or more double parallelogram mechanisms 160 may be used to constrain the motion of each runway panel 108 ( 102 ).
[0066] In yet another embodiment of the present invention as shown in FIG. 10 , the panels are replaced with an appropriately sized and relatively flat surfaced chain like or belt like structures 170 that cover a commonly used underlying support structure which is in turn attached to the support and control elements 106 ( 109 ) with or without one or more of the aforementioned motion constraining mechanisms. The use of such chain or belt like surface structures allow for a smoother travel of the tire, similar to the case of shorter panels shown in FIG. 4 . For example, a continuous belt segment would in effect act similar to panels with very small lengths.
[0067] Hereinafter, the above types of runway surface elements are referred to as runway panels without intending to limit them to any one of the above designs. To those skilled in the art, numerous other “runway panel” design configurations that allow relatively smooth vertical displacement of the underlying surface as the vehicle tire travels over such “runway panel” and thereby affect deformation of appropriately positioned elastic potential energy storage elements similar to the spring elements 110 are possible and are intended to be covered by the present disclosure.
[0068] The runway panels are elastically supported by spring elements that are positioned between the panels and the runway foundation. The elastic (spring) elements may take any form, for example, they may be constructed in a helical or similar form by spring wires of various cross-sections, or they may be formed as torsion or bending springs, torsion bars, or any of their combinations. To optimally control the vertical movement of the runway panels, the spring rates, i.e., the relationship between the applied vertical force and the resulting vertical displacement of the runway panel may be linear or nonlinear. The spring elements may be positioned directly between the runway panels and the runway foundation or act on the mechanical elements that provide motion constraint to the panels. In general, various spring types and configurations may be used to provide various elastic responses upon the application of load (mostly vertical) at certain points on the panel, i.e., to provide the desired effective spring rates in response to the vertical displacement and rotation about an axis directed in the transverse direction.
[0069] The potential energy storage elements can also be the structural elements disclosed in U.S. Pat. No. 6,054,197, the contents of which are incorporated herein by its reference. In general, as shown in FIG. 11 , the weight 115 of the tire 112 deforms the structural element 200 which is disposed between each panel 102 ( 108 ) and the runway base 107 to store a potential energy therein. The structural element may also itself serve as the braking element where displaced fluid 202 from the interior of the structural element (caused by the deformation) is captured in a reservoir 204 and restricted from returning to the cavity 202 , such as by closing a valve 206 while the structural element is deformed. The structural element 200 is released or reset (extended) by removing the restriction, such as by opening the valve 206 to allow the fluid to flow back into the cavity 202 . Preferably, the structural elements 200 are remotely controlled by a processor 208 operatively connected to a solenoid which operates the opening and closing of the valves 206 . The amount of deformation the structural elements undergo can also be controlled and varied by the processor by controlling the amount that the valves 206 open (i.e., the orifice size is varied). A structural element 200 corresponding to a valve 206 that is partially opened will be more rigid and thus undergo less deformation than a structural element having a corresponding valve 206 that is fully open.
[0070] Each runway panel assembly, i.e., the runway panel, its motion constraining mechanisms and the elastic elements, viscous and dry friction based damping elements, are also equipped with one-way locks, that as the elastic elements are deformed under load, they are held in their maximum deformed position and are substantially prevented from regaining their original configuration as the load is lifted. Such one-way locking mechanisms may be placed at any appropriate position between the runway panels and the foundation or between the runway panels and the mechanical motion constraining elements. The one-way locking mechanisms may also be positioned in parallel with one or more of the elastic elements, or may be constructed as an integral part of one or more of the elastic or damping elements. Regardless of their design and the method of integrating them into the runway panel assembly, the one-way locks serve one basic function. This basic function is to “lock” the depressed runway panels in place and prevent them from “springing” back to their original position. In other words, as the airplane or other vehicle tire displaces a runway panel, the work done by the force exerted on the displacing surface panels (mostly vertically and some in rotation) is to be stored in the spring elements 110 ( 200 ) as potential energy. The function of the aforementioned one-way lock mechanisms is to “lock in” this potential energy by preventing the spring elements 110 ( 200 ) from moving back to their original position. The potential energy stored in the spring elements 110 ( 200 ), neglecting all other commonly present energy losses due to friction, etc., is equal to the kinetic energy that is transferred from the airplane or other vehicle to the spring elements 110 ( 200 ). In general, one or more elastic elements of various types may be used on each runway panel and one or more of the spring elements may be initially preloaded. The primary purpose of preloading of the elastic elements is to reduce the amount of vertical and/or rotational displacement of the runway panels for a given applied load. Another function of selectively preloading one or more of the elastic elements is to create the load-displacement (rotation) characteristics that is optimal or close to optimal for the operation of the runway.
[0071] In the preferred embodiment of this invention, the effective spring rates of each runway panel assembly and the spring preloading are adjustable remotely. The spring rates and preloads may obviously be adjustable manually, particularly for runways that are only used with a few similar types of airplanes.
[0072] In general, the runway panel assemblies are designed such that they do not require motion damping elements such as viscous dampers for their proper operation such as to prevent the bouncing action upon initial tire contact. Such dampers are used to control the response of the runway panel assemblies to the speed of application of the tire load. In any case, minimal damping is desired to be used to make the RAR most responsive to high-speed vehicles. In addition, if the stored potential energy in the elastic elements are intended to be used or harvested, minimal damping is desired to be employed since such dampers would convert a portion of the kinetic energy of the plane into heat, i.e., a type of energy that is difficult to harness as compared to potential energy stored in elastic elements.
[0073] On the other hand, certain runway panel assemblies, particularly those that are located at or close to the portion of the runway over which the plane travels at high speeds, may be desired to be equipped with motion damping elements such as viscous dampers that are appropriately positioned to provide resistance to the displacement and/or rotation of the runway panels for smooth operation. The effective damping rates of these elements are also desired to be adjustable remotely, manually and if possible by a closed-loop control loop.
[0074] When the runway is intended to slow down airplanes upon landing, the plane may first land on a regular (fixed) runway segment and then enter the RAR segment to be slowed or be brought to complete stop. In such cases, it is important that the transition between the two runway segments be as smooth as possible. Such smooth transitions are readily obtained, e.g., by providing higher spring rates for the initial highway panels and/or hinging them to the edge of the regular runway segment and then gradually decreasing the panel spring rates to achieve maximum deflection, i.e., maximum vertical displacement of the runway panels under tire load. As the result, the vehicle begins to slow down smoothly as it enters the RAR segment. Then, as the plane continues to travel along the RAR segment, the runway panels begin to be displaced vertically to their maximum set amount, and the kinetic energy of the plane continues to be transferred to the spring elements, while a certain (usually much smaller) portion of the kinetic energy is dissipated in the viscous damping and/or brake like friction elements. The plane will loose no control since the slowing down process does not involve any skidding or reduction or loss of contact friction between the tires and the runway surface. This is in total contrast with sand-filled roads and collapsible concrete runways that would form certain “pathways” along which the tires are forced to travel. Of course, the RAR may also constitute the entire runway which may be much smaller in length then a conventional runway for the same size aircraft.
[0075] Once the plane has been slowed down to the desired speed or has been brought to rest, the braking mechanisms of the runway panels can be released to slowly bring the panels to their original position. To make the movement smooth and prevent vibration, viscous damping or friction elements may be engaged during this return movement. Alternatively, energy transformation means such as electric generators may be used to transform the stored energy in the elastic elements into usable electric energy.
[0076] On the other hand, the potential energy stored in the elastic element of the runway panels may be used to accelerate a plane during its takeoff. The process is the reverse of the slowing down process. Here, as the tire moves over a depressed runway panel, the panel brakes are released in a controlled manner from the back of each panel to the front as the tire moves over the panel, thereby pushing the plane forward and transferring the potential energy stored in the elastic elements to the plane as kinetic energy. By properly releasing the braking mechanisms, it is possible to transfer most of the stored potential energy to the plane. This process has the effect of allowing the plane to travel along a runway with a downward incline, thereby transferring the potential energy of the plane due to the total drop in the plane elevation to the plane in the form of kinetic energy.
[0077] Both landing and taking off processes using RAR can be seen to be highly energy efficient. During the landing, minimal or no braking is required. During takeoff, a large portion of the required kinetic energy can be absorbed from the RAR. By appropriate selection of the RAR parameters, planes are able to land and take off in relatively short runways. Such runways can therefore be also very useful for the construction of emergency landing and takeoff strips and for aircraft carrier.
[0078] In general, elastomeric or hydraulic type of shock absorbers and bumpers may be used to limit the motion of the runway panels 108 ( 102 ) in the vertical direction to the designated depth H ( 105 ), or prevent excessive lateral motion of the panels or the motion constraint mechanisms, etc. In all situations, such elements are provided in order to smoothly bring these components to a stop and without a sudden shock. For the case of the depth 105 limiting stops, the allowable depth H ( 105 ) is preferably adjustable by a control system that adjusts the system parameters for each particular vehicle and initial speed and operating condition. Such a controller is described above with regard to FIG. 11 , however, similar control methods may be employed in the other embodiments discussed herein for controlling any or all system parameters.
[0079] In general, the spring elements 110 are preferably preloaded to reduce the required depth H ( 105 ). It is also generally preferable to have springs with nonlinear force displacement characteristics of the general form shown in FIG. 9 so that as the deformation is increased, the effective spring rate is also increased. Such a spring rate characteristic allows the springs to also act as effective stops as the maximum desired depth H ( 105 ) is approached. The general shape of the desired spring displacement versus spring force curve 163 is shown in FIG. 9 . The amount of preloading force is indicated by 165 . The spring rate, i.e., the slope of the curve 163 increases with spring displacement. For a given displacement 161 of the spring, the corresponding spring rate k ( 162 ) is given by the slope of the tangent 164 at that point on the curve 163 . As can be observed, by proper selection of the spring 110 , as the displacement is increased (in this case as it reaches the desired amount H ( 105 ), the spring rate becomes very large (somewhere to the right of the point 161 ), where the spring turns into an effective stop.
[0080] In general, more than one wide runway panel 108 ( 102 ) is desired to cover the width of the runway. By utilizing narrower panels, the effective mass that is displaced as the tire moves over a panel is reduced, thereby allowing for the RAR panels to respond quickly. As a result, faster moving vehicles can be accommodated. In which case, the panels are desired to be hinged together as described for the longitudinal sides of the panels, together with similar elastic elements to allow the length variations due to the relative rotation of the panels. In one embodiment of the present invention, the aforementioned relative rotation of the panels along their hinged side edges is allowed. Such an option would provide a certain amount of barrier that the tires have to climb in order to move in the direction of the width of the runway. Such a barrier is desired, particularly if the vehicle is damaged or if the pilot is having problems controlling the vehicle. In an emergency situation, by allowing the depth H ( 105 ) to become larger, a larger stabilizing barrier can be provided for keeping the vehicle on the runway. For such emergency situations, auxiliary barriers positioned on the sides of the runway may also be activated to increase the height of the side barriers. On the other hand, in normal situations, the aforementioned relative rotation of the panels is preferably limited or is totally prevented by the provided hinges and the motion constraining mechanisms.
[0081] Although the RAR is described above having static parameters, such parameters can be variable, either adjusted manually or automatically in response to sensed characteristics. For Example, the RAR can be equipped with sensors for detection of the position, size, and/or velocity of the vehicle before entering the RAR. The information detected by one or more sensors is then input to a processor, which adjusts the parameters of the RAR before the vehicle enters the RAR. The sensors can also continue to monitor the vehicle as it travels on the RAR and adjust the parameters thereof accordingly. For example, one parameter that can be adjusted based on the sensed characteristics is the spring rates of the spring elements 110 . Means for adjusting spring rates of spring elements are well known in the art, such as helical or other passive springs in combination with pressurized gas springs. Another example of a parameter that can be adjusted, is the viscous damping rates of the damper can also be adjusted based on the sensed characteristics. Means for adjusting damping rates are well known in the art, such as providing an electrically actuated orifice change or by using magneto-restrictive fluids in fixed orifice fluid dampers. Yet another example of a parameter that could be adjusted in response to the sensed characteristics is to provide moving stops that vary the amount of movement of the panels 102 , 108 . The stops can be moved by any means known in the art, such as by using electrically or hydraulically driven lead screws. These characteristics can be varied as a whole (applied to all of the panels 102 , 108 , or applied to selective panels 102 ( 108 ) and done manually or under the control of a central processor or control unit.
[0082] Referring now to FIG. 13 , there is shown a tire 300 capable of transferring the kinetic energy of a vehicle to potential energy thus slowing the vehicle as if it were going up an inclined surface. The tire 300 has support and control assemblies 109 similar to that described above with regard to the RAR. Those skilled in the art will appreciate that as the tire 300 rotates, the elastic elements contained in the support and control assemblies 109 are deformed and held in the deformed state (such as with a braking element) similar to that described above with regard to the RAR. As the tire 300 further rotates such that the deformed elastic elements are no longer in contact with the roadway (or runway) 101 , the braking of the deformed elastic elements is released and the process repeats as the tire continues to roll over the roadway 101 . Those skilled in the art will appreciate that such a tire, when activated, slows the vehicle as if the vehicle was traveling up an inclined surface. Those skilled in the art will further appreciate that the tire can also be used to accelerate the vehicle. When the tire 300 is used during normal operation the elastic elements are either not engaged so as not to deform or permitted to freely deform without being held in the deformed state.
[0083] While there has been shown and described what is considered to be preferred embodiments of the invention, it will, of course, be understood that various modifications and changes in form or detail could readily be made without departing from the spirit of the invention. It is therefore intended that the invention be not limited to the exact forms described and illustrated, but should be constructed to cover all modifications that may fall within the scope of the appended claims. | A roadway upon which a wheeled vehicle travels is provided. The roadway including a movable surface extending in a direction of the vehicle's travel and a potential energy transfer arrangement operatively connected to the movable surface for transferring a stored potential energy associated with the movable surface into kinetic energy upon movement of the movable surface thereby propelling the vehicle. A method for accelerating a vehicle upon a roadway is also provided. | 1 |
BACKGROUND
[0001] 1. Field
[0002] The invention relates to automotive structural joints and methods of making the same.
[0003] 2. Discussion
[0004] Certain structural panels and joints are known. As an example, U.S. Pat. No. 3,256,669 to Seiwert discloses a reinforced metal panel assembly made by using a pair of metal panels and an intermediate core of suitable material such as plywood, balsa, Masonite, wall-board, aluminum or any of the other light metals. The panels are joined to produce a compressive interference fit between the panels and the core. The metal panels may be designated as an inner and an outer panel depending on their intended position in a finished structure.
[0005] As another example, U.S. Pat. No. 4,791,765 to Noggle discloses a synthetic material structural body panel comprising a synthetic material. An aperture extends through the synthetic material panel. A metal attachment plate fixedly engages the synthetic material and spans the aperture. Noggle also discloses a joint between the synthetic material structural body panel and another structural body panel. The joint comprises a metal attachment plate as described above and means, such as spot welding, for securing the metal attachment plate to the other structural body panel.
[0006] As yet another example, U.S. Pat. No. 6,291,792 to Fussnegger et al. discloses a welded joint made between a sheet-steel component and a sheet-aluminum component by way of a lap or web weld. Hat-like clip parts are pushed through openings in the sheet-aluminum component. The clip parts are welded at their bottom to the sheet-steel component and overlap an exposed flat side of the sheet-aluminum component with their flanges. An adhesive is introduced into a gap situated between the clip part and the sheet-aluminum component.
SUMMARY
[0007] A joint for an automotive vehicle may comprise a composite member having opposing surfaces and including an aperture extending therethrough and a first metal member positioned adjacent to one of the opposing surfaces of the composite member. The joint may also include a second metal member positioned adjacent to the other of the opposing surfaces of the composite member. The second metal member includes a portion extending into the aperture of the composite member. The portion extending into the aperture is fixedly attached with the first metal member. The joint may further include a first uncured adhesive layer disposed between one of (i) the first metal member and the one of the opposing surfaces of the composite member and (ii) the second metal member and the other of the opposing surfaces of the composite member.
[0008] A structural member for an automotive vehicle may include a composite panel having opposing sides and a surface defining an aperture therethrough. The structural member may also include first and second metal panels respectively adhesively bonded to the opposing sides of the composite panel. The first and second metal panels each include a button formed thereon. The buttons each extend into the aperture and are attached together.
[0009] A structural joint for an automotive vehicle may comprise a composite member having opposing surfaces and including an aperture extending therethrough, a first member adhered with one of the opposing surfaces of the composite member and a second member adhered with the other of the opposing surfaces. The second member includes a portion extending into the aperture of the composite member. The portion extending into the aperture is fixedly attached with the first member.
[0010] A method of forming a structural joint for an automotive vehicle may include applying an adhesive to at least one of a first member and a first surface of a composite member, placing the first member in contact with the first surface of the composite member and applying an adhesive to at least one of a second member and a second surface of the composite member opposite the first surface. The method may also include positioning a divot portion of the second member within an aperture of the composite member, placing the second member in contact with the second surface of the composite member, attaching the divot portion of the second member with the first member and curing the adhesives.
[0011] While example embodiments in accordance with the invention are illustrated and disclosed, such disclosure should not be construed to limit the claims. It is anticipated that various modifications and alternative designs may be made without departing from the scope of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] FIG. 1 is a perspective view of an embodiment of a portion of an automotive structural joint.
[0013] FIG. 2A is an exploded view, in cross-section, of the automotive structural joint of FIG. 1 .
[0014] FIG. 2B is an assembly view, in cross-section, of the automotive structural joint of FIG. 1 .
DETAILED DESCRIPTION
[0015] Referring now to FIG. 1 , a composite member 10 is sandwiched between members 12 , 14 to form a structural joint 16 . The composite member 10 may comprise any synthetic material suitable for use as a structural member for an automotive vehicle. For example, the composite member 10 may comprise a non-reinforced or fiber-reinforced thermoplastic and/or a thermoset plastic. The material comprising the composite member 10 may be selected based on the particular application for which it is intended. Suitable commercially available fibers include glass fibers, carbon fibers, etc. and any combination thereof. Of course, other suitable materials may be used.
[0016] The members 12 , 14 may comprise any suitable metal, e.g., steel, aluminum, etc., for use in automotive applications. For example, the member 12 may comprise a steel doubling plate and the member 14 may comprise a structural steel rail configured to act as a load bearing member of a vehicle body.
[0017] The composite member 10 of a chosen synthetic material may be formed or shaped into the desired configuration using any suitable technique. Such suitable techniques include injection molding, resin transfer molding and compression molding. The technique used may depend on the material employed. For example, compression molding techniques may be applied to sheet molding compounds (SMC) including a fiber-reinforced thermoset polyester.
[0018] In the embodiment of FIG. 1 , buttons 18 , e.g., divots, depressions, etc., are provided in the member 12 and extend into respective apertures 20 in the composite member 10 . The buttons 18 may be stamped or otherwise integrally formed with the member 12 . In other embodiments, the buttons 18 may be provided in the member 14 in addition to, or instead of, the member 12 . In certain of these embodiments, some of the buttons 18 provided in the members 12 , 14 may extend into the same apertures 20 (and, for example, meet in a middle of the apertures 20 ) while other of the buttons 18 may extend into different apertures 20 . For example, the buttons 18 provided in the members 12 , 14 may extend into every other of the apertures 20 in an alternating fashion. Of course, other configurations are also possible.
[0019] The buttons 18 of FIG. 1 are sized relative to the apertures 20 so as to provide a clearance fit. In other embodiments, the buttons 18 may be sized relative to the apertures 20 so as to provide an interference fit.
[0020] The structural joint 16 illustrated in FIG. 1 includes three buttons positioned generally along an axis, A. Of course, a greater or fewer number of the buttons 18 may be used. In other embodiments, the buttons 18 may be positioned to form a grid or other desired pattern/layout.
[0021] In some embodiments, a portion of each of the buttons 18 contact and are welded, as discussed below, to the member 14 . In other embodiments, the buttons 18 may be riveted, bolted or otherwise mechanically fastened to the member 14 . Additionally, the buttons 18 (and the apertures 20 ) may be of sufficient size so as to permit several welds per button 18 .
[0022] The buttons 18 may be formed so that portions of the member 12 lie flush against the composite member 10 . For example, the buttons 18 may have a depth approximately equal to the thickness of the composite member 10 . The buttons 18 may also be formed so that portions of the member 12 are spaced away from the composite member 10 . For example, the buttons 18 may have a depth that is greater than the thickness of the composite member 10 . Other configurations and arrangements are also possible.
[0023] The apertures 20 may be formed during the initial manufacture of the composite member 10 . For example, the apertures 20 may be cut into the composite member 10 or may be provided by appropriate design of the tooling used in molding the composite member 10 .
[0024] The apertures 20 of FIG. 1 have a shape complimentary to the buttons 18 . In other embodiments, the apertures 20 may, for example, have a shape non-complimentary to the buttons 18 . For example, the apertures 20 may have a square shape and the buttons 18 may have a conical shape.
[0025] As discussed below, the members 12 , 14 are bonded with the composite member 10 so as to span, e.g., cover, the apertures 20 of the composite member 10 . The buttons 18 of FIG. 1 engage the apertures 20 to, inter alia, locate the member 12 relative to the composite member 10 . When the members 12 , 14 are attached with the composite member 10 , at least a portion of the composite member 10 surrounding the apertures 20 is sandwiched between the members 12 , 14 . The members 12 , 14 may be adhesively bonded, as discussed below, or otherwise fixedly engaged with the composite member 10 so as to cover the apertures 20 .
[0026] Adhesives for bonding the members 12 , 14 with the composite member 10 may include an epoxy, urethane, acrylic, etc., applied, for example, as a tape, liquid, paste or pressure sensitive adhesive. Any suitable adhesive, however, may be used. The selection of a suitable adhesive may depend on the material comprising the composite member 10 , the cost of the adhesive, ease of processing the adhesive, the intended use of the structural joint 16 , etc. The adhesives may be cured by heat, room-temperature chemical reaction, induction or any other curing method.
[0027] In some embodiments, gaps between the members 10 , 12 and 10 , 14 may be determined by glass beads, wires, stand-offs on any of the members 10 , 12 , 14 , assembly fixturing, etc.
[0028] As apparent to those of ordinary skill, the composite member 10 and the members 12 , 14 may have any configuration suitable for the environment and/or intended use of the structural joint 16 . For example, in embodiments where the member 14 is curved, the composite member 10 and member 12 may also be formed with corresponding curves to mate with the member 14 . Likewise, the apertures 20 and buttons 18 may have any suitable configuration for the environment and/or intended use of the structural joint 16 . For example, the apertures 20 may have a triangular, square or other suitable shape. Similarly, the buttons 18 may have a mating triangular, square or other suitable shape similar or dissimilar to the shape of the apertures 20 .
[0029] Referring now to FIGS. 2A and 2B , the following may be performed to assemble the structural joint 16 . An adhesive layer 22 is applied to one or both of the composite member 10 and the member 14 . The member 14 is then placed in contact with the composite member 10 . An adhesive layer 24 is applied to one or both of the composite member 10 and the member 12 . The member 12 is positioned relative to the composite member 10 such that the button 18 is in registration with the aperture 20 . The member 12 is then placed in contact with the composite member 10 . The button 18 is fixedly attached, e.g., spot welded, with the member 14 at weld 26 . The adhesive layers 22 , 24 are then cured to bond the composite member 10 with the members 12 , 14 . Because the button 18 is fixedly attached with the member 14 prior to curing, there is no need for fixturing or other machinery to hold the members 12 , 14 in place relative to one another during the curing process.
[0030] In other embodiments, the adhesive layer 24 may first be applied to one or both of the composite member 10 and the member 12 . The member 12 may then be positioned relative to the composite member 10 such that the button 18 is in registration with the aperture 20 . The member 12 may then be placed in contact with the composite member 10 . The adhesive layer 22 may next be applied to one or both of the composite member 10 and the member 14 . The member 14 may then be placed in contact with the composite member 10 . Welding, for example, of the button 18 with the structural member 14 and curing of the adhesive layers 22 , 24 may follow. In still other embodiments, the adhesive layers 22 , 24 may be applied at the same time, etc., prior to fixedly attaching and curing. Alternatively, a single adhesive layer may also be applied prior to fixedly attaching and curing.
[0031] The structural joint 16 may be used in a variety of applications. For example, the structural joint 16 may be used to join a composite floorpan of an automotive vehicle to a steel frame rail, dash-panel and rear floor of the vehicle. The structural joint 16 may also be used to join a composite hood inner panel of an automotive vehicle to steel hinge reinforcements of the vehicle, etc.
[0032] While only certain embodiments of the invention have been illustrated and described, it is not intended that these embodiments illustrate and describe all possible forms of the invention. Rather, the words used in the specification are words of description rather than limitation, and it is understood that various changes may be made without departing from the spirit and scope of the invention. | A joint for an automotive vehicle may be formed by applying an adhesive to at least one of a first member and a first surface of a composite member, placing the first member in contact with the first surface of the composite member, applying an adhesive to at least one of a second member and a second surface of the composite member, positioning a divot portion of the second member within an aperture of the composite member, placing the second member in contact with the second surface of the composite member, attaching the divot portion of the second member with the first member and curing the adhesives. | 1 |
FIELD OF THE INVENTION
[0001] The present invention relates to health and personal hygiene equipment and methods of controlling such equipment. More particularly, the present invention relates to oral irrigators and methods of controlling such equipment.
BACKGROUND OF THE INVENTION
[0002] Oral irrigators for discharging a high-pressure fluid stream into a user's oral cavity are well known in the art and are useful for promoting oral hygiene and health. For example, a particularly effective oral irrigator is disclosed in U.S. patent application Ser. No. 10/749,675 which is hereby incorporated by reference in its entirety into the present application.
[0003] It is advantageous for an oral irrigator to discharge a fluid stream at a select pulse rate that is generally constant. For example, a particularly useful constant pulse rate is 1200 cycles per minute.
[0004] Depending on the user and the part of the oral cavity being impacted by the fluid stream, a high-pressure fluid stream or a low-pressure fluid stream may be preferred. Thus, it is preferable to offer oral irrigators with an ability to vary the pressure of the fluid stream discharging from the oral irrigator. Prior art oral irrigators have attempted to meet this need by adjusting pumping speed. Unfortunately, this approach results in an inability of the oral irrigator to provide a generally constant pulse rate.
[0005] There is a need in the art for an oral irrigator that offers discharge pressure control while still maintaining a generally constant pulse rate. There is also a need in the art for a method of controlling the pressure of a fluid stream discharging from the oral irrigator while still maintaining a generally constant pulse rate.
SUMMARY OF THE INVENTION
[0006] The present invention, in one embodiment, is a handheld oral irrigator comprising a fluid reservoir, a pump, a pressure control assembly, and a nozzle. The pump includes a suction side and a discharge side. The suction side is in fluid communication with the fluid reservoir. The pressure control assembly includes a casing and a member displaceable within the casing. The casing has an inlet and an outlet. The inlet is in fluid communication with the discharge side of the pump, and the nozzle is in fluid communication with the outlet of the casing.
[0007] In one embodiment, the member is longitudinally displaceable within the casing. In one embodiment, the oral irrigator also includes an actuator for displacing the member within the casing and wherein the member comprises a portion that extends through the casing to couple to the actuator. In one embodiment, the portion of the member is an arm that extends through a longitudinally extending slot in the casing. In one embodiment, a fluid flow path extending from the inlet to the outlet is modifiable between a first route that extends along at least a portion of the member and a second route that does not.
[0008] The present invention, in one embodiment, is an oral irrigator comprising a pump, a discharge nozzle and a pressure control. The pump has a generally constant operating speed and feeds the discharge nozzle. The pressure control is adapted to modify a discharge pressure at the nozzle without a significant change in pump speed. The pressure control modifies a level of fluid flow restriction between the pump and the nozzle. In one embodiment, the pressure control modifies the diameter of a fluid flow path extending through the pressure control. In one embodiment, the pressure control modifies the length of a fluid flow path extending through the pressure control. In one embodiment, the pressure control modifies the number of direction changes of a fluid flow path extending through the pressure control.
[0009] The present invention, in one embodiment, is an oral irrigator comprising a pump and a pressure adjustment assembly. The pump supplies a nozzle. The pressure adjustment assembly is configured to provide a first fluid flow path associated with a high nozzle discharge pressure and a second fluid flow path associated with a low nozzle discharge pressure. The pressure adjustment assembly is located between the pump and nozzle.
[0010] In one embodiment, the first fluid flow path offers a more direct route to the nozzle than the second fluid flow path. In one embodiment, the first fluid flow path has a length that is shorter than a length of the second fluid flow path. In one embodiment, the second fluid flow path has a diameter that is smaller than a diameter of the first fluid flow path.
[0011] In one embodiment, the pressure adjustment assembly includes a casing and a member displaceable within the casing. The casing includes an orifice and the member includes an orifice. The second fluid flow path extends through both orifices. The first fluid flow path extends only through the orifice of the casing.
[0012] In one embodiment, the pressure adjustment assembly includes a casing and a member displaceable within the casing. A portion of the second fluid flow path extends circumferentially about at least a portion of the member. In one embodiment, the member is generally cylindrical and includes a groove extending about at least a portion of the circumferential outer surface of the member. The casing includes an inlet orifice that aligns with the groove to form a portion of the second fluid flow path. The member includes a longitudinally extending center lumen in fluid contact with the groove via an orifice extending through a wall of the member.
[0013] The present invention, in one embodiment, is an oral irrigator comprising a pump and a pressure adjustment assembly. The pump supplies a nozzle. The pressure adjustment assembly comprises a first fluid flow friction setting associated with a high nozzle discharge pressure and a second fluid flow friction setting associated with a low nozzle discharge pressure.
[0014] The present invention, in one embodiment, is a method of controlling a nozzle discharge pressure of an oral irrigator that includes a pump that feeds a nozzle. The method comprises modifying a fluid flow friction value of a fluid flow path between the pump and nozzle by modifying the fluid flow path. In one embodiment, the fluid flow path is modified by changing its length. In one embodiment, the fluid flow path is modified by changing its diameter. In one embodiment, the fluid flow path is modified by changing its number of direction deviations.
[0015] The present invention, in one embodiment, is an oral irrigator including a handle portion and a faceplate. The faceplate is selectively attachable to the handle portion to customize an appearance of the oral irrigator.
[0016] While multiple embodiments are disclosed, still other embodiments of the present invention will become apparent to those skilled in the art from the following detailed description, which shows and describes illustrative embodiments of the invention. As will be realized, the invention is capable of modifications in various aspects, all without departing from the spirit and scope of the present invention. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not restrictive.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] FIG. 1 is a top isometric view of the handheld oral irrigator.
[0018] FIG. 2 is a top isometric view of the handheld oral irrigator.
[0019] FIG. 3 is a control side elevation of the handheld oral irrigator.
[0020] FIG. 4 is a reservoir side elevation of the handheld oral irrigator.
[0021] FIG. 5 is a right side elevation of the handheld oral irrigator as if viewed from the direction of arrow A in FIG. 3 .
[0022] FIG. 6 is a left side elevation of the handheld oral irrigator as if viewed from the direction of arrow B in FIG. 3 .
[0023] FIG. 7 is a top plan view of the handheld oral irrigator.
[0024] FIG. 8 is a bottom plan view of the handheld oral irrigator.
[0025] FIG. 9 is a section elevation of the handheld oral irrigator as taken along section line 9 - 9 in FIG. 4 .
[0026] FIG. 10 is an isometric view of a motor side of the handheld oral irrigator with the outer housing of the handle portion removed to show the internal elements of the irrigator.
[0027] FIG. 11 is the same type of view as illustrated in FIG. 10 , except of a pump side of the handheld oral irrigator.
[0028] FIG. 12 is a longitudinal section through the pump.
[0029] FIG. 13 is an isometric of view of the motor/pump/transmission arrangement with the rest of the irrigator 10 hidden for clarity purposes.
[0030] FIG. 14 is an isometric view of the pressure control valve assembly 85 with the majority of the rest of the handheld oral irrigator 10 hidden for clarity purposes.
[0031] FIG. 15 is a side elevation of the same elements depicted in FIG. 14 , as viewed from the same direction as FIG. 6 .
[0032] FIG. 16 is a side elevation of the same elements depicted in FIG. 14 , as viewed from the same direction as FIG. 4 .
[0033] FIG. 17A is a longitudinal cross section of the pressure control valve assembly as taken along section line 17 - 17 in FIG. 15 and wherein a spool is in a rearward location (i.e., a high discharge pressure position) within the valve cylinder.
[0034] FIG. 17B is the same view depicted in FIG. 17A , except the spool is in a forward location (i.e., a low discharge pressure position) within the valve cylinder.
[0035] FIG. 18A is a longitudinal cross section of the pressure control valve assembly as taken along section line 18 - 18 in FIG. 16 and wherein the spool is in a rearward location (i.e., a high discharge pressure position) within the valve cylinder.
[0036] FIG. 18B is the same view depicted in FIG. 18A , except the spool is in a forward location (i.e., a low discharge pressure position) within the valve cylinder.
[0037] FIG. 19 is a side view of the pressure control valve assembly as shown in FIG. 15 , except the discharge tube, nozzle and control button are hidden for clarity purposes.
[0038] FIG. 20 is an isometric view of the valve assembly wherein the discharge tube, nozzle and control button are hidden for clarity purposes.
[0039] FIG. 21 is an isometric view of the spool and yoke.
[0040] FIG. 22 is an isometric latitudinal cross section taken along section line 22 - 22 in FIG. 15 .
[0041] FIG. 23 is a similar view as illustrated in FIG. 10 , except various components are shown in an alternate configuration.
[0042] FIG. 24 is a similar view as illustrated in FIG. 11 , except various components are shown in an alternate configuration.
[0043] FIG. 25 is a bottom perspective view of a reservoir of the handheld oral irrigator.
[0044] FIG. 26 is a rear perspective view of a removable faceplate of the handheld oral irrigator.
DETAILED DESCRIPTION OF THE INVENTION
[0045] The subject invention, in one embodiment, is a handheld oral irrigator 10 that allows a user to adjust the discharge pressure of the irrigator generated fluid stream while maintaining the pulse rate of the fluid stream. Thus, the handheld oral irrigator 10 is advantageous over the prior art because it allows a user to adjust the fluid stream discharge pressure to suit the user's comfort preference, while still allowing the oral irrigator to supply the fluid stream at a preferred or most effective pulse rate (e.g., 1200 cycles per minute).
[0046] For a discussion of the overall external configuration of one embodiment of the handheld oral irrigator 10 , reference is made to FIGS. 1-8 . FIGS. 1 and 2 are top isometric views of the handheld oral irrigator 10 . FIG. 3 is a control side elevation of the handheld oral irrigator 10 . FIG. 4 is a reservoir side elevation of the handheld oral irrigator 10 . FIG. 5 is a right side elevation of the handheld oral irrigator 10 as if viewed from the direction of arrow A in FIG. 3 . FIG. 6 is a left side elevation of the handheld oral irrigator 10 as if viewed from the direction of arrow B in FIG. 3 . FIG. 7 is a top plan view of the handheld oral irrigator 10 . FIG. 8 is a bottom plan view of the handheld oral irrigator 10 .
[0047] As shown in FIGS. 1-7 , in one embodiment, the irrigator 10 includes a handle portion 15 and a nozzle 20 with an orthodontic tip at its distal end. The nozzle 20 extends from a top end of the handle portion 15 . The nozzle 20 is detachable from the handle portion 15 via a nozzle release button 25 located on the top of the handle portion 15 .
[0048] As illustrated in FIGS. 1-6 , in one embodiment, the handle portion 15 has a modified hourglass shape that gradually narrows from a wide base 30 (the proximal end of the irrigator 10 ) to a narrow gripping area 35 and gradually widens from the narrow gripping area 35 to a moderately wide top 40 (the distal end of the irrigator 10 ). The hourglass shape is aesthetically pleasing and ergonomically shaped to accommodate a user's hand, which in one embodiment will be a child or adolescent hand.
[0049] As indicated in FIGS. 1 , 2 and 4 - 8 , in one embodiment, the handle portion 15 includes a reservoir 45 that forms a part of the base 30 . The reservoir 45 is removable from the rest of the handle portion 15 and includes a fill port 50 near the bottom of the reservoir 45 . To fill the reservoir with fluid, the reservoir 45 may be disengaged and removed from the rest of the handle portion 15 , the cap of the fill port 50 is opened, and a fluid is flowed into the reservoir 45 via the open fill port 50 . Once the reservoir 45 is filled, the cap is closed on the fill port 50 and the reservoir 45 is reattached to the rest of the handle portion 15 .
[0050] As can be understood from FIGS. 1 , 2 and 4 - 8 , the reservoir 45 may be filled while still attached to the rest of the handle portion 15 . To do this, the cap of the fill port 50 is opened and a fluid is flowed into the reservoir 45 via the open fill port 50 . Once the reservoir 45 is filled, the cap is closed.
[0051] For a discussion regarding disengaging the reservoir 45 from the rest of the handle portion, reference is made to FIGS. 8 and 25 , wherein FIG. 25 is a bottom perspective view of the reservoir of the handheld oral irrigator. As best shown in FIGS. 8 and 25 , the reservoir 45 includes a leaf spring latch 47 molded into a lower portion of the reservoir 45 to releasably secure the reservoir 45 to the handle portion 15 . The leaf spring latch 47 is biased to engage the handle portion 15 when the reservoir 45 is joined with the handle portion 15 . To disengage the leaf spring latch 47 from the handle portion 15 , the user moves a latch portion 49 of the leaf spring latch 47 in the direction indicated by an arrow formed, printed, or placed on the leaf spring latch 47 . In one embodiment, the reservoir 45 moves downwardly relative to the handle portion 15 when the leaf spring latch 47 is disengaged from the handle portion 15 .
[0052] Referring again to FIGS. 1 , 3 and 5 - 7 for a continued discussion of the overall external configuration of the handheld oral irrigator, in one embodiment, a control side of the gripping area 35 includes an on/off control 52 , a pressure control 54 , and a removable faceplate 56 that surrounds the locations of the two controls 52 , 54 . The on/off control 52 allows a user to turn on or shut off the irrigator 10 . To turn the irrigator 10 on, the on/off control 52 , which can be a slide, button, etc., is moved (e.g., slid or depressed) to complete an electrical circuit between the irrigator's internal power source and its motor. To turn the irrigator 10 off, the control 52 is moved again to break the electrical circuit.
[0053] The pressure control 54 allows a user to adjust the discharge pressure of a fluid stream discharging from the distal tip of the nozzle 20 . In one embodiment, the nozzle release button 25 is located on the reservoir side opposite from the controls 50 , 52 , which helps limit accidental release of the nozzle 20 by accidental pressing or other engagement of the nozzle release button 25 when the user operates the controls 50 , 52 .
[0054] The removable faceplate 56 can be replaced with other faceplates having other colors or designs, thereby allowing the user to customize the appearance of the irrigator 10 as preferred. In one embodiment, the handheld oral irrigator 10 is sold or provided with multiple faceplates 56 of various designs and colors. The user selects their preferred faceplate and mounts it on the handle portion 15 .
[0055] As shown in FIG. 26 , which is a rear perspective view of the removable faceplate of the handheld oral irrigator, the removable face plate 56 has two or more L-shaped tabs 410 a , 410 b for receipt in corresponding slots or grooves defined in the handle portion 15 of the oral irrigator 10 to join the removable faceplate 56 to the handle portion 15 . When joined together, the short legs of the tabs 410 a , 410 b are received in the slots or grooves defined in the handle portion 15 to maintain the joined relationship between the removable faceplate 56 and the handle portion 15 .
[0056] To disconnect the removable faceplate 56 from the handle portion 15 , the removable faceplate 56 is sufficiently flexible such that a user can deflect the edges 415 , 420 of the removable faceplate 56 inward in order disengage the tabs 410 a , 410 b from the handle portion 15 to pull the faceplate 56 away from the handle portion 15 . As a user moves the edges 415 , 420 of the removable faceplate 56 inwardly, the short legs of the tabs 410 a , 410 b are removed from the slots or grooves in the handle portion 15 , thereby allowing the user to remove the removable faceplate 56 from the handle portion 15 .
[0057] To join the removable faceplate 56 to the handle portion 15 , a user deflects the edges 415 , 420 of the removable faceplate 56 inwardly and abuts a rear facing surface 425 of the removable faceplate 56 against the handle portion 15 . When the removable faceplate 56 abuts the handle portion 15 in the proper location and orientation, the short legs of the tabs 410 a , 410 b generally align with the grooves or slots in the handle portion 15 . In one embodiment, the handle portion 15 has a recessed surface surrounding the controls 50 , 52 to aid a user in properly locating and orienting the removable faceplate 56 relative to the handle portion. 15 . Once the removable faceplate 45 abuts the handle portion 56 in the proper location and orientation, the user stops squeezing the edges 415 , 420 of the removable faceplate inwardly, thereby causing the short legs of the tabs 410 a , 410 b , which are biased to move outwardly by the internal forces generated by inward movement of the edges 415 , 420 of the removable faceplate 56 , to enter into the grooves or slots defined in the handle portion 15 .
[0058] Referring again to FIGS. 1 , 3 and 5 - 7 for a continued discussion of the overall external configuration of the handheld oral irrigator, the reservoir side of the gripping area 35 includes a soft over molded grip area 58 , which in one embodiment, includes gripping bumps 60 , a textured gripping surface, or other grip enhancing features.
[0059] As illustrated in FIGS. 1 and 3 , in one embodiment, a charging plug 63 exits in the handle portion 15 near the base 30 . The charging plug 63 is used to place an external power source in electrical communication with an internal power source (e.g., battery) located within the handle portion 15 .
[0060] For a discussion of the overall internal configuration of one embodiment of the handheld oral irrigator 10 , reference is made to FIGS. 9-11 , 23 and 24 . FIG. 9 is a section elevation of the handheld oral irrigator 10 as taken along section line 9 - 9 in FIG. 4 . FIG. 10 is an isometric view of a motor side of the handheld oral irrigator 10 with the outer housing 65 of the handle portion 15 removed to show the internal elements of the irrigator 10 . FIG. 11 is the same type of view as illustrated in FIG. 10 , except of a pump side of the handheld oral irrigator 10 . FIG. 23 is a similar view as illustrated in FIG. 10 , except various components are shown in an alternate configuration. FIG. 24 is a similar view as illustrated in FIG. 11 , except various components are shown in an alternate configuration.
[0061] As shown in FIG. 9 , the irrigator 10 includes an outer housing 65 that forms the exterior surface of the handle portion 15 . The housing 65 encloses a motor 70 , a pump 75 , a transmission 77 , a rechargeable NiCad battery 80 , and a pressure control valve assembly 85 . In one embodiment as illustrated in FIGS. 10 and 11 , the motor 70 and pump 75 are located in a side-by-side arrangement near the base 30 , the transmission 77 is located below the motor 70 and pump 75 , the battery 80 is located above the motor 70 and pump 75 , and the valve assembly 85 is located above the battery 80 . In another embodiment as illustrated in FIGS. 23 and 24 , the battery 80 is located near the base 30 , the motor 70 and pump 75 are located above the battery 80 , the transmission 77 is located above the motor 70 and pump 75 , and the valve assembly 85 is located above the transmission 77 . The transmission 77 couples the motor 70 to the pump 75 to convert the rotational output of the motor 70 into the longitudinally reciprocating movement of the pump's piston 120 .
[0062] As illustrated in FIG. 9 , the removable reservoir 45 forms a significant part of a lower side of the handle portion 15 . The fill port 50 opens into the reservoir 45 , and the reservoir 45 extends under a portion of the housing 65 enclosing the motor 70 and pump 75 . A transfer tube 90 extends from a bottom level of the reservoir 45 to a seal coupling 95 . In one embodiment, the transfer tube 90 is part of the reservoir. In another embodiment, the transfer tube 90 is separate from the reservoir 45 . When the reservoir 45 is coupled to the rest of the handle portion 15 , the seal coupling 95 sealing mates with a bottom end of a suction tube 100 , which leads to a suction port 105 of the pump 75 , as best understood from FIGS. 11 and 24 . Thus, the reservoir 45 is placed in fluid communication with the suction side of the pump 75 .
[0063] As indicated in FIGS. 10 and 11 , and FIGS. 23 and 24 , the motor 70 , pump 75 , transmission 77 and valve assembly 85 are coupled to a chassis plate 110 longitudinally extending through the housing 65 of the handle portion 15 . In one embodiment, the controls 52 , 54 , motor 70 and the battery 80 are located on one side of the plate 110 , and the pump 70 and valve assembly 85 are located on the other side of the plate 110 .
[0064] As can be understood from FIGS. 9 and 11 , the suction tube 100 is detachably sealably coupled to the seal coupling 95 by coupling the reservoir 45 to the rest of the housing 65 of the handle portion 15 such that the free end of the suction tube 100 is received in the seal coupling 95 . As shown in FIG. 11 , fluid traveling form the reservoir 45 to the distal end of the nozzle 20 is drawn through the transfer tube 90 , into the suction tube 100 at the seal coupling 95 and to the suction port 105 of the pump 75 .
[0065] As can be understood from FIG. 12 , which is a longitudinal section through the pump 75 , when a piston 120 moves rearwardly in a cylinder 115 of a cylinder casing 118 (rearward movement indicated by arrow X in FIG. 12 ), a discharge wafer 121 of a discharge wafer valve arrangement is forced against a discharge valve seat 122 and the fluid is drawn through the suction port 105 of a suction casing 107 of the pump 75 , past a suction wafer 108 forming a suction wafer valve arrangement, and into the cylinder 115 . When the piston 120 moves forwardly (as indicated by arrow Y in FIG. 12 ), the suction wafer 108 is forced against the suction valve seat 125 and the fluid is forced past the discharge wafer 121 , into a discharge port 130 of a discharge casing 135 of the pump 75 , and into a discharge tube 140 leading to the valve assembly 85 , as illustrated in FIGS. 11 and 24 .
[0066] In one embodiment, as depicted in FIGS. 11 and 12 , the pump 75 is formed from three casings (e.g., the suction casing 107 , cylinder casing 118 and discharge casing 135 ). In one embodiment, the three casings 107 , 118 , 135 are held together via a joining mechanism. For example, in one embodiment, a screw 145 (illustrated in FIG. 11 ) is received in screw receiving holes 146 (shown in FIG. 12 ) in the three casings 107 , 118 , 135 .
[0067] For a discussion of the motor/pump/transmission arrangement, reference is made to FIG. 13 , which is an isometric of view of the motor/pump/transmission arrangement with the rest of the irrigator 10 hidden for clarity purposes. As shown in FIG. 12 , a pinion gear 150 extends from the motor 70 to drive a gear 155 carrying a cam 160 . A piston rod 165 (see FIGS. 12 and 13 ) extends between the piston 120 and a cam follower end 170 of the piston rod 165 . The cam follower end 170 receives the cam 160 , and as the cam 160 is caused to rotate, the cam follower 170 and cam 160 act to convert the rotational movement of the motor 70 into longitudinal reciprocal displacement of the piston 120 within the cylinder 115 .
[0068] For a discussion of the pressure control valve assembly 85 , reference is made to FIGS. 14-22 . FIG. 14 is an isometric view of the pressure control valve assembly 85 with the majority of the rest of the handheld oral irrigator 10 hidden for clarity purposes. FIG. 15 is a side elevation of the same elements depicted in FIG. 14 , as viewed from the same direction as FIG. 6 . FIG. 16 is a side elevation of the same elements depicted in FIG. 14 , as viewed from the same direction as FIG. 4 . FIG. 17A is a longitudinal cross section of the pressure control valve assembly 85 as taken along section line 17 - 17 in FIG. 15 and wherein a spool 180 is in a rearward location (i.e., a high discharge pressure position) within the valve cylinder 185 . FIG. 17B is the same view depicted in FIG. 17A , except the spool 180 is in a forward location (i.e., a low discharge pressure position) within the valve cylinder 185 . FIG. 18A is a longitudinal cross section of the pressure control valve assembly 85 as taken along section line 18 - 18 in FIG. 16 and wherein the spool 180 is in a rearward location (i.e., a high discharge pressure position) within the valve cylinder 185 . FIG. 18B is the same view depicted in FIG. 18A , except the spool 180 is in a forward location (i.e., a low discharge pressure position) within the valve cylinder 185 . FIG. 19 is a side view of the pressure control valve assembly 85 as shown in FIG. 15 , except the discharge tube 140 , nozzle 20 and control button 54 are hidden for clarity purposes. FIG. 20 is an isometric view of the pressure control valve assembly 85 wherein the discharge tube 140 , nozzle 20 and control button 54 are hidden for clarity purposes. FIG. 21 is an isometric view of the spool 180 and yoke 190 . FIG. 22 is an isometric latitudinal cross section taken along section line 22 - 22 in FIG. 15 .
[0069] As can be understood from FIGS. 14-18B and 22 , fluid pumped through the discharge tube 140 from the pump 75 enters an inlet 210 of the pressure control valve assembly 85 . As depicted in FIG. 19 and FIG. 22 , in one embodiment, to enter the valve cylinder 185 , the fluid passes through slot openings 215 in the cylinder wall 220 .
[0070] As can be understood from FIGS. 17A-18B , a spool 180 is located in the cylinder 185 and longitudinally displaceable within the cylinder 185 . As illustrated in FIG. 21 , the spool 180 is cylindrically shaped with a pair of arms 257 extending outwardly and rearwardly from a middle portion of the spool 180 . A lumen 258 extends longitudinally through the length of the spool 180 . The free ends of the arms 257 are received in pivot holes 259 in a yoke 261 . The distal end of the spool 180 includes a pair of o-ring receiving grooves 260 , a fluid groove 265 positioned between the o-ring grooves 260 , and an orifice 275 extending between the fluid groove 265 and the lumen 270 . The proximal end of the spool 180 includes an o-ring receiving groove 277 .
[0071] As indicated in FIGS. 17A and 18A , when the spool 180 is located rearwardly in the cylinder 185 , the fluid passes through the slot openings 215 (see FIGS. 19 and 20 ) and directly from the front of the cylinder 185 , through the valve assembly outlet 225 , through the lumen 230 of the nozzle 20 , and out the distal tip of the nozzle 20 as a high discharge pressure fluid stream. As indicated in FIGS. 17B , 18 B and 21 , when the spool 180 is located forwardly in the cylinder 185 , the fluid passes through the slot openings 215 (see FIGS. 19 and 20 ) and between the fluid groove 265 and the inner circumferential surface of the cylinder 185 , through the orifice 275 , into the lumen 258 of the spool 180 , through the valve assembly outlet 225 , through the lumen 230 of the nozzle 20 , and out the distal tip of the nozzle 20 as a low discharge pressure fluid stream.
[0072] As can be understood from FIGS. 17A-20 , when the spool 180 is in the forward position within the cylinder 185 (i.e., the low discharge pressure position), the fluid flow passing through the pressure control valve assembly 85 must overcome a substantially increased frictional resistance as compared to when the spool 180 is in the rearward position within the cylinder 185 (i.e., the high discharge pressure position). Accordingly, when the spool 180 is in the low discharge pressure position, the pressure control valve assembly 85 creates a substantially high-pressure drop in the fluid flow passing through the assembly 85 as compared to when the spool 180 is in the high discharge pressure position. Thus, without having to adjust the operating speed of the pump 75 , a user may adjust the discharge pressure of a fluid stream emanating from the nozzle 20 of the oral irrigator 10 by adjusting the position of the spool 180 within the cylinder 185 . Accordingly, the discharge pressure may be substantially modified by a user without causing a substantial change in the preferred pulse rate of the fluid stream.
[0073] As can be understood from FIGS. 17A-20 , moving the spool 180 from the high discharge pressure position (see FIGS. 17A and 18A ) to the low discharge pressure position (see FIGS. 17B and 18B ) modifies, in several ways, the fluid flow path through the discharge pressure control assembly 85 and, as a result, the fluid flow path between the pump 75 and the nozzle 20 . First, moving the spool 180 from the high to the low discharge pressure position increases the length of the fluid flow path because the flow is diverted about the fluid groove 265 , through the orifice 275 and through the lumen 258 before the flow can pass through the cylinder outlet 225 to the nozzle 20 . Second, moving the spool 180 from the high to the low discharge pressure position substantially decreases the diameters or flow areas of the fluid flow path because the diameters or flow areas of the fluid groove 265 , orifice 275 , and lumen 258 are substantially smaller than the internal diameter or flow area of the cylinder 185 . Third moving the spool 180 from the high to the low discharge pressure position increases the number of direction deviations the fluid flow must undergo because the fluid must travel a tortuous route around the groove 265 and through the orifice 275 and lumen 258 before the flow can pass through the cylinder outlet 225 to the nozzle 20 .
[0074] Each of these modifications to the fluid flow path brought about by moving the spool 180 from the high to low discharge pressure position increases the magnitude of the fluid flow friction between the pump 75 and the nozzle 20 . Accordingly, although the pump 75 continues to operate at generally the same speed and provides a fluid stream at generally the same pulse rate, because the spool 180 moves from the high to the low discharge pressure position within the cylinder 185 , the discharge pressure of the fluid stream at the distal end of the nozzle 20 decreases from a high to low discharge pressure.
[0075] Research has indicated that some fluid stream pulse rates are more effective than other pulse rates. For example, in one embodiment of the subject invention, the pump 75 of the oral irrigator 10 cycles at a rate such that it discharges a fluid stream out the nozzle 20 that has a pulse rate of 1000-1600 pulses per minute and, in one embodiment, 1100-1400 pulses per minute and, in one embodiment, 1200 pulses per minute. As discussed in U.S. Pat. No. 3,227,158 issued to Mattingly, which is incorporated by reference herein in its entirety, a pulse rate of 1000-1600 pulses per minute has been found to be the most effective pulse rates for the purposes of oral hygiene and health. Other highly effective pulse rates for the purposes of oral hygiene and health also include 1100-1400 pulse per minute and 1200 pulses per minute.
[0076] The pressure control feature of the subject invention is advantageous because it allows a user to adjust the fluid stream discharge pressure to suit the user's comfort preferences while maintaining the pulse rate generally at a preferred pulse rate. For example, regardless of whether the pressure control valve assembly 85 is set to cause a low or high discharge pressure fluid stream to emanate from the nozzle 20 , the fluid stream will have a preferred number of pulses per minute (e.g., 1000-1600 pulses per minute, 1100-1400 pulses per minute, 1200 pulses per minute, etc.).
[0077] For a discussion of the cylinder's configuration, reference is again made to FIGS. 14 and 17 A- 20 . As best understood from FIGS. 14 , 19 and 20 , the cylinder 185 of the pressure control valve assembly 185 includes a proximal portion 185 a received within a collar portion 185 b of a distal portion 185 c . A slot 300 extends longitudinally along the sides of the cylinder 185 , and the arms 257 of the spool 180 extend through the slots 300 to couple with the arms of the yoke 261 . As indicated in FIGS. 17A-18B , the cylinder 185 is hollow to receive the spool 180 , and the proximal end of the cylinder proximal portion 185 c is walled-off such that when a fluid flows into the lumen 258 of the spool 180 , the fluid impacts the proximal end of the cylinder proximal portion 185 c to establish a back pressure condition within the pressure control valve assembly 85 . As can be understood from FIGS. 17A and 17B , the o-rings 260 , 277 prevent fluid from escaping the cylinder 185 through the slots 300 .
[0078] For a discussion of the linkage 305 used to cause the spool 180 to displace within the cylinder 185 , reference is again made to FIGS. 9 , 14 , 15 , 18 A- 21 . As best understood from these figures, the linkage 305 includes the yoke 261 and the pressure control 54 . The yoke 261 includes a pair of arms, and each arm has a pivot hole 259 near its free end. The pivot holes 259 pivotally receive therein the free ends of the spool arms 257 . The yoke includes an arcuately slotted tongue 310 opposite the yoke arms for pivotally receiving therein a ball 315 extending from the pressure control 54 .
[0079] As indicated in FIG. 9 , in one embodiment, the pressure control 54 is a slide supported by the housing 65 of the handle portion 15 of the irrigator 10 . As illustrated in FIGS. 19 and 21 , the yoke 261 has a rocker portion 320 from which the tongue 310 extends. As shown in FIGS. 18A and 18B , the rocker portion 320 resides within a hole or slot 325 in the chassis plate 110 , which allows the tongue 310 to rock towards the nozzle 20 or towards the base 30 , depending on how the slide 54 is displaced along the housing 65 .
[0080] As indicated in FIG. 18A , when the slide 54 is shifted towards the nozzle 20 , the tongue 310 is rocked towards the nozzle 20 thereby causing the yoke 261 to pivot about the hole 325 in the chassis plate 110 such that the yoke arms move towards the base 30 and pull the spool arms 257 towards the base 30 , which causes the spool 180 to move towards the base 30 (i.e., the spool 180 moves into the high discharge pressure position). As indicated in FIG. 18B , when the slide 54 is shifted towards the base 30 , the tongue 310 is rocked towards the base 30 thereby causing the yoke 261 to pivot about the hole 325 in the chassis plate 110 such that the yoke arms move towards the nozzle 20 and pull the spool arms 257 towards the nozzle 20 , which causes the spool 180 to move towards the nozzle 20 (i.e., the spool 180 moves into the low discharge pressure positions).
[0081] For a discussion regarding the elements of the nozzle release, reference is again made to FIGS. 9 , 14 , 15 and 18 A- 20 . As illustrated in these figures, the nozzle release button 25 is coupled to a collar 350 having an opening 355 centered about the hole 360 of the nozzle base receiving cylinder 368 , which extends from the cylinder outlet 225 . The proximal end of the nozzle 20 is received in the receiving cylinder 368 and the collar 350 . The collar 350 is biased into a nozzle base groove 370 by a spring 380 . The groove 370 extends about the circumference of the nozzle base. To release or disengage the collar 350 from the nozzle base groove 370 to allow the nozzle 20 to be withdrawn from the receiving cylinder 368 , the nozzle release button 25 is depressed against the biasing force of the spring 380 , which causes the collar 350 to shift out of engagement with the groove 370 . The nozzle 20 is then withdrawn from the cylinder 368 .
[0082] As can be understood from the preceding discussion, the oral irrigator of the present invention is advantageous because it allows a user to adjust the discharge pressure of the fluid stream emanating from the oral irrigator without bringing about a significant change in the pulse rate of the fluid stream. Thus, the oral irrigator can continue to supply a fluid stream at a preferred pulse rate regardless of the discharge pressure selected by the user.
[0083] Although the present invention has been described with reference to preferred embodiments, persons skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention. The invention is limited only by the scope of the following claims. | The present invention is an oral irrigator comprising a pump, a discharge nozzle and a pressure control. The pump has a generally constant operating speed and feeds the discharge nozzle. The pressure control is adapted to modify a discharge pressure at the nozzle without a significant change in pump speed. The pressure control modifies a level of fluid flow restriction between the pump and the nozzle. The modification of the level of fluid flow restriction is accomplished by modifying aspects of a fluid flow path extending through the pressure control. The aspects modified include the diameter, length and/or number of direction changes of the fluid flow path. | 0 |
This application is a division of application Ser. No. 07/692,766, filed Apr. 29, 1991, U.S. Pat. No. 5,106,928.
BACKGROUND OF THE INVENTION
This invention relates to a novel organoboron complex initiator system and an acrylic adhesive composition containing this initiator. More particularly this invention involves a two-part initiator system comprising in one-part a stable organoboron amine complex and in the second part an organic acid destabilizer or activator. This initiator system is especially useful in elastomeric acrylic adhesive compositions.
Adhesive compositions including acrylic adhesives such as solutions of elastomeric polymers in soluble polymerizable acrylic or methacrylic monomers are well known in the art. These compositions which are especially known for their toughening properties generally include a redox system which comprises a catalyst or initiator, an accelerator and an activator to initiate cure, as well as other additives such as adhesion promoters, chelators, cross-linking agents, thickeners and plasticizers. Two-part acrylic adhesives where an activator is added as a separate second component are widely used and are known for curing speed as well as toughness. The catalyst or initiator typically used in these adhesives are free-radical initiators of the organic peroxy or hydroperoxy type, perester or peracid type.
Many known adhesive systems, such as the epoxies, require a thermal cure to obtain desirable properties, while others that do not, usually require prolonged cure times. In comparison, the adhesive composition with organoboron amine complex initiator of this invention cures at room temperature and reaches high tensile strength in a short period of time. Additionally, the adhesive composition of this invention has shown exceptional stability on ageing while exhibiting both high tensile strength and high peel strength.
SUMMARY OF THE INVENTION
This invention involves a novel two-part organoboron amine complex initiating system useful in elastomeric acrylic adhesives compositions to provide better and faster room temperature curing thereof.
The organoboron initiating system of this invention is a two-part system comprising:
A) a stabilized organoboron amine complex of the formula: ##STR1## where R, R 1 and R 2 are alkyl of 1 to 10 carbon atoms or phenyl, R 3 and R 4 are hydrogen or alkyl of 1 to 10 carbon atoms, or ##STR2## where R 5 and R 6 are hydrogen or alkyl of 1 to 10 carbon atoms, m is 2 to 10 and n is 1 to 6, and
B) an organic acid activator having the formula:
R--COOH
where R is hydrogen, alkyl or alkenyl of 1 to 8 carbon atoms, or aryl having 6 to 10 carbon atoms.
DETAILED DESCRIPTION OF THE INVENTION
The stabilized organoboron amine complex of the structure (I) which comprises one part of the initiator of this invention is made by combining an organoboron compound with a primary or secondary amine or polyamine containing primary or secondary amines. The organoboron compound has the formula: ##STR3## where R, R 1 and R 2 are alkyl of 1 to 10 carbon atoms or phenyl, preferably alkyl of 1 to 4 carbons. In this formula, the alkyl groups may be straight or branch chained and the phenyl group may contain substituents such as alkyl, alkoxy or halogen. Illustrative compounds of this type include, e.g., trimethylboron, triethylboron, tri-n-butylboron, tri-sec-butylboron and tri-isobutylboron.
The amine which is used in forming the organoboron amine complex (I) may be any primary or secondary amine or polyamine containing a primary or secondary amine, or ammonia and having the following formula: ##STR4## where R 3 and R 4 are hydrogen or alkyl of 1 to 10 carbon atoms, or ##STR5## where R 5 and R 6 are hydrogen or alkyl of 1 to 10 carbon atoms, m is 2 to 10, and n is 1 to 6. The alkyl groups in this formula may be straight or branch chained. Preferably, the R groups noted in the amine will be hydrogen or alkyl of 1 to 4 carbon atoms, m will be 2 to 6 and more preferably 2 to 3 and n will be 1 to 2. Illustrative compounds of this type include, e.g., n-octylamine, 1,6-diaminohexane, diethylamine, dibutylamine, diethylene triamine, dipropylene diamine, ammonia, 1,3-propylenediamine and 1,2-propylenediamine.
The stabilized amine complex can be prepared by combining a solution of the organoboron with the amine under an inert atmosphere with cooling as needed.
The activator used as the second part or component of the initiator system will be a compound which will destabilize or liberate the free organoboron compound by removing the amine group and thereby allow it to initiate the polymerization process. This activator is an organic acid having the formula:
R--COOH
where R is H, alkyl or alkenyl of 1 to 8 and preferably 1 to 4 carbon atoms, or aryl of 6 to 10, preferably 6 to 8 carbon atoms. It is further understood that the alkyl or alkenyl group of this organic acid may be straight or branch chained and the aryl may contain substituents such as alkyl, alkoxy or halogen. Illustrative examples of compounds of this type include: acrylic acid, methacrylic acid, benzoic acid, and p-methoxybenzoic acid.
Generally the initiator system of this invention will comprise the organoboron amine complex and an effective destabilizing amount of the organic acid activator. More particularly from about 0.1:1 to 200:1 parts by weight of acid to amine complex and preferably from about 1:1 to 24:1 parts by weight of acid to amine complex may be used.
The organoboron initiator of this invention is particularly useful in acrylic adhesive compositions and especially solutions of elastomeric or rubber polymers in compatible polymerizable acrylic monomers.
The polymerizable acrylic monomer may be monofunctional, polyfunctional or a combination thereof.
One class of polymerizable monomers useful in the present compositions correspond to the general formula: ##STR6## wherein R is selected from the group consisting of hydrogen methyl, ethyl, ##STR7## R' is selected from the group consisting of hydrogen, chlorine, methyl and ethyl;
R" is selected from the group consisting of hydrogen, hydroxy, and ##STR8## m is an integer equal to at least 1, e.g., from 1 to 8 or higher and preferably from 1 to 4 inclusive;
n is an integer equal to at least 1, e.g., from 1 to 20 or more; and
p is one of the following: 0 or 1.
Monomers useful in this invention and which come within the above general formula include, for example, ethylene glycol dimethacrylate, ethylene glycol diacrylate, polyethylene glycol diacrylate, tetraethylene glycol dimethacrylate, diglycerol diacrylate, diethylene glycol dimethacrylate, pentaerythritol triacrylate, trimethylolpropane trimethacrylate, and other polyether diacrylates and dimethacrylates.
The above class of monomers is in essence described in U.S. Pat. No. 3,043,820 issued Jul. 10, 1962 (to R. H. Krieble).
A second class of polymerizable monomers useful in the present compositions correspond to the general formula: ##STR9## wherein R represents hydrogen, chlorine, methyl or ethyl; R' represents alkylene with 2-6 carbon atoms; and, R" represents (CH 2 ) m in which m is an integer of from 0 to 8, or ##STR10## and n represents an integer of from 1 to 4.
Typical monomers of this class include, for example, dimethacrylate of bis(ethylene glycol) adipate, dimethacrylate of bis(ethylene glycol) maleate, dimethacrylate of bis(diethylene glycol) phthalate, dimethacrylate of bis(tetraethylene glycol) phthalate, dimethacrylate of bis(tetraethylene glycol) sebacate, dimethacrylates of bis(tetraethylene glycol) maleate, and the diacrylates and chloroacrylates corresponding to said dimethacrylates, and the like.
The above class of monomers is in essence described in U.S. Pat. No. 3,457,212 issued Jul. 22, 1969 (Sumitomo Chemical Company, Ltd.)
Also useful herein are monomers which are isocyanate-hydroxyacrylate or isocyanate-aminoacrylate reaction products which may be characterized as acrylate terminated polyurethanes and polyureides or polyureas. These monomers correspond to the general formula: ##STR11## wherein X is selected from the group consisting of --O-- and ##STR12## and R is a member selected from the group consisting of hydrogen and lower alkyl of 1 to 7 carbon atoms; A represents the organic residue of an active hydrogen containing acrylic ester wherein the active hydrogen has been removed, the ester being hydroxy or amino substituted on the alkyl portion thereof and the methyl, ethyl and chlorine homologs thereof; n is an integer from 1 to 6 inclusive; and B is a mono- or polyvalent organic radical selected from the group consisting of alkyl, alkylene, alkenyl, cycloalkyl, cycloalkylene, aryl, aralkyl, alkaryl, poly(oxyalkylene), poly(carboalkoxyalkylene), and heterocyclic radicals both substituted and unsubstituted.
Typical monomers of this class include the reaction product of mono- or polyisocyanate, for example, toluene diisocyanate, with an acrylate ester containing a hydroxy or amino group in the non-acrylate portion thereof, for example, hydroxyethyl methacrylate.
The above class of monomers is in essence described in U.S. Pat. No. 3,425,988 issued Feb. 4, 1969 (Loctite Corporation).
Another class of monomers useful in the present application are the mono- and polyacrylate and methacrylate esters of bisphenol type compounds. These monomers may be described by the formula: ##STR13## where R 1 is methyl, ethyl, carboxyalkyl or hydrogen; R 2 is hydrogen, methyl or ethyl; R 3 is hydrogen, methyl or hydroxyl; R 4 is hydrogen, chlorine, methyl or ethyl; and n is an integer having a value of 0 to 8.
Representative monomers of the above-described class include: dimethacrylate and diacrylate esters of 4,4'-bis-hydroxyethoxy-bisphenol A; dimethacrylate and diacrylate esters of bisphenol A; etc. These monomers are essentially described in Japanese Patent Publication No. 70-15640 (to Toho Chemical Manuf. Ltd.).
In addition to the monomers already described, other useful monomers are monofunctional acrylate and methacrylate esters and the substituted derivatives thereof such as hydroxy, amide, cyano, chloro, and silane derivatives. Such monomers include, for example, methyl acrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, isobornyl methacrylate, hydroxyethyl methacrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, butyl acrylate, n-octyl acrylate, 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, decylmethacrylate, dodecyl methacrylate, cyclohexyl methacrylate, tert-butyl methacrylate, acrylamide, N-methylolacrylamide, diacetone acrylamide, N-tert-butyl acrylamide, N-tert-octyl acrylamide, N-butoxyacrylamide, gamma-methacryloxypropyl trimethoxysilane, 2-cyanoethyl acrylate, 3-cyanopropyl acrylate, tetrahydrofurfuryl methacrylate, tetrahydrofurfuryl chloroacrylate, glycidyl acrylate, glycidyl methacrylate, and the like.
The monomers useful herein are seen to be polymerizable monomers having one or more acrylic or substituted acrylic groups as a common, unifying characteristic, and for convenience may be generically termed acrylic monomers.
The elastomer or rubber polymers may be any of the typically available synthetic rubbers that are soluble in the monomer such as those based on polyisoprenes, polybutadienes, polyolefins, polyurethane, polyesters, etc. Examples of elastomeric materials include homopolymers such as polybutadiene, polyisoprene and polyisobutylene; diene type copolymers such as butadiene/styrene copolymer, butadiene/acrylonitrile copolymer, butadiene/methyl methacrylate copolymer and butadiene/alkyl acrylate copolymer; ethylene/vinyl acetate copolymers; ethylene/alkyl acrylate copolymers (1-8 carbons in the alkyl group), rubbery polyalkyl acrylates or copolymers thereof; polyurethane; chlorinated polyethylenes; and EPDM (ethylene/propylene/diene terpolymers).
The elastomers of these structures may contain a functional group at one or both ends or within a particular segment or repeating unit of the copolymer. Among the suitable functional groups are vinyl, epoxy, carboxyalkyl, and mercapto groups. Other functional groups may be employed as deemed useful as determined by routine experimentation.
One preferred group of elastomers are the block copolymers. Several such block copolymers are manufactured by Shell Chemical Company under the tradename Kraton and by Firestone under the tradename Stereon. In particular, Stereon 840A, a poly(styrene-b-butadiene-b-styrene) block copolymer, has been found to be especially useful in the instant adhesive composition. Other preferred block copolymers of this type are available under the tradename Solprene 416, manufactured by Phillips Petroleum Co.
The monomer solution containing the elastomer or rubbery polymer is commonly prepared by dissolving the elastomer in the monomer, which may be in the form of a syrup. In some cases, the monomer solution may be prepared by extracting a rubbery polymer from a latex of the rubbery polymer in water, as used for suspension polymerization, and then dissolving in the monomer.
The amount of the acrylic monomer to be used in this invention may vary somewhat depending on the specific properties desired but generally about 10 to 90% by weight of the composition and preferably about 15 to 80% by weight is used. Adjustment within these ranges are easily made within the skill of the art. The elastomer is generally present in amounts of about 5 to 80% by weight and preferably about 20 to 60% by weight of the composition.
The second part of the initiator which contains the acid activator, preferably may also contain a peroxy or hydroperoxy component having the formula:
R--OOH
where R is hydrogen, alkyl of 1 to 10 preferably 4 to 10 carbon atoms or aryl or alkaryl of 6 to 14, preferably 6 to 10 carbon atoms. Illustrative compounds of this type are t-butyl hydroperoxide and cumene hydroperoxide. Typically these hydroperoxy compounds which aid in the initiation of polymerization are used in the initiator system in amounts of about 0.2:1 to 100:1 and preferably from about 0.4:1 to 20:1 parts by weight of hydroperoxy to amine complex.
The organoboron amine complex used in an adhesive composition in accordance with this invention generally comprises from about 0.1 to 5% by weight of the total composition and preferably from about 0.5 to 2.5% and the organic acid activator comprises from about 0.5 to 20%, preferably from about 1 to 12% by weight of the total composition. When a hydroperoxy compound is used in the adhesive composition, it generally comprises from about 0.2 to 10% by weight of the total composition and preferably from about 0.5 to 2%.
Other additives useful in elastomeric acrylic adhesives of this type, such as adhesion promoters, chelators, cross-linking agents, inhibitors, activators such as N,N-dimethyltoluidine as well as thickeners, plasticizers and diluents may also be used in the adhesive compositions of this invention.
The organoboron initiator system as described above comprises a two component system. When used in the acrylic rubber compositions of this invention generally the two parts are mixed in equal quantities of the monomer-polymer solution, but this may vary at the discretion of the user. That is, the stabilized organoboron compound is added to a solution of the elastomer or rubber polymer dissolved in the polymerizable acrylic monomer and the organo acid activator and optional hydroperoxy compound are added as a second part which also may be in a solution of the rubber polymer in acrylic monomer.
Adhesive compositions of this invention are particularly useful in structural and semi-structural applications such as speaker magnets, metal-metal bonding (automotive) glass-metal bonding, glass-glass bonding, circuit board component bonding, selected plastic to metal, glass, wood, etc. and electric motor magnets.
In the following examples, which are merely illustrative of the embodiments of this invention, all parts and percentages are given by weight and all temperatures are in degrees Celsius unless otherwise noted.
EXAMPLE I
Preparation of Organoboron Amine Complexes
Into a 3-neck flask containing a stirrer, condenser, thermometer and a nitrogen purge, 11.1 g (0.15 m, 50% excess) of 1,3-propylene diamine was added and the nitrogen purge continued while 100 ml of 1 molar solution (0.1 m) of tributylboron in tetrahydrofuran was further added. A mild exotherm developed and the temperature was kept below about 40° C. by cooling as necessary. When the addition was complete, the mixture was stirred for about 0.5 hour and transferred to a bottle previously flushed with nitrogen. This amine complex is identified below as initiator XII as well as other amine complexes prepared in a similar manner using the amines and amounts indicated.
______________________________________AMINE AMOUNT INITIATOR NO.______________________________________ethylene diamine 6.0 g (0.10 m) Iethylene diamine 9.0 g (0.15 m) IIethylene diamine 12.0 g (0.20 m) III1,2-propylene diamine 11.1 g (0.15 m) IVn-octylamine 19.4 g (0.15 m) V1,6-diaminohexane 17.4 g (0.15 m) VIdiethylenetriamine 10.3 g (0.10 m) VII1,3-propylene diamine.sup.1 7.4 g (0.10 m) VIII4-aminomethylpyridine 10.8 g (0.10 m) IX3-aminomethylpyridine 10.8 g (0.10 m) Xdiethylamine 10.95 g (0.15 m) XI1,3-propylene diamine 11.1 g (0.15 m) XII______________________________________ .sup.1 1 molar solution of triethylboron in tetrahydrofuran used
EXAMPLE II
Preparation of Adhesive Composition
An adhesive formulation was prepared consisting of two parts that were mixed just prior to use. The first part contained the monomer-polymer syrup and the stabilized organoboron amine complex initiator from Example I. The second part contained a similar monomer-polymer syrup and an acid activator or reagent that destabilized the organoboron amine complex liberating the free organoboron. When mixed with the first part polymerization was initiated. The two adhesive composition parts were:
______________________________________Part IStereon 840A (styrene-butadiene block copolymer) 30 partsIsobornyl methacrylate 70 partsOrganoboron amine initiator No. 12.sup.1 4 partsPart IIStereon 840A 30 partsIsobornyl methacrylate 61 partsMethacrylic acid 5 partsCumene hydroperoxide (CHP) 4 parts______________________________________ .sup.1 1 molar solution in tetrahydrofuran
Approximately equal portions of Parts I and II were mixed and applied to steel plates and allowed to cure. Tensile shear strength measurement on the adhesive bond was made according to the ASTM standard method D1002-72(1973) and found to be 2000 psi.
Additional adhesive formulations were prepared in a similar manner using the components as identified below along with the resulting tensile strength determined is described above for the formed adhesive bond.
__________________________________________________________________________ INITIATOR BOND TENSILERUBBER (%) (%) % ACID.sup.1 % CHP.sup.2 STRENGTH PSI__________________________________________________________________________Stereon 840a (20) XII (0.5) 10 0.1 1875Stereon 840a (25) VIII (0.5) 1 1 1550Kraton 1107 (20).sup.3 II (0.5) 10 1 1850Kraton 1107 (20) II (0.25) 10 1 1350Kraton 1107 (20) II (1.0) 10 1 2100Hycar 4051 (10).sup.4 IV (0.5) 10 1 1200Kraton 1122 (25).sup.5 VI (0.5) 1 1 1500Stereon 840A (20) I (0.5) 0.5 1.7 1500 also contains 13% octyl acrylateStereon 840A (30) VIII (0.5) 10 1 2700 monomer was tetrahydrofurfuryl methacrylate__________________________________________________________________________ .sup.1 methacrylic acid .sup.2 cumene hydroperoxide .sup.3 styreneisoprene .sup.4 polyacrylic rubber polymer .sup.5 styreneisoprene
EXAMPLE III
Similar adhesive formulations were prepared as in Example II using an amine complex of 1,3 propylene diamine and triethyl boron as the initiator (initiator No. VIII). The formulations contained two-parts as in Example II that were mixed just prior to use and had the following compositions:
__________________________________________________________________________Part ISample No. Initiator Rubber.sup.1 Monomer A Monomer B Monomer C__________________________________________________________________________3A-I 2 parts 25 parts 60 parts 15 parts -- (IBOMA) (OMA)3B-I 2 parts 25 parts 60 parts 15 parts -- (IBOMA) (OMA)3C-I 2 parts 25 parts 60 parts 15 parts -- (IBOMA) (ODA)3D-I 2 parts 25 parts 60 parts 15 parts -- (IBOMA) (HDDA)3E-I 2 parts 25 parts 60 parts 15 parts -- (IBOMA) (HDDMA)3F-I 2 parts 30 parts -- -- 70 parts (THFMA)3G-I 2 parts 30 parts -- -- 70 parts (THFMA)3H-I 2 parts 30 parts -- -- 70 parts (THFMA)3I-I 2 parts 30 parts -- -- 70 parts (THFMA)3J-I 2 parts 30 parts 55 parts -- 15 parts (IBOMA) (HPMA)__________________________________________________________________________
__________________________________________________________________________Part IISample No. Rubber.sup.1 Monomer A Monomer B Acid CHP__________________________________________________________________________3A-II 25 parts 50 parts 15 parts 10 parts -- (THFMA) (OMA) (MAA)3B-II 25 parts 50 parts 15 parts 10 parts -- (IBOMA) (OMA) (MAA)3C-II 25 parts 50 parts 15 parts 10 parts -- (THFMA) (ODA) (MAA)3D-II 25 parts 50 parts 15 parts 10 parts -- (THFMA) (HDDA) (MAA)3E-II 25 parts 50 parts 15 parts 10 parts -- (THFMA) (HDDMA) (MAA)3F-II 30 parts 60 parts -- 10 parts 0.125 parts (THFMA) (MAA)3G-II 30 parts 60 parts -- 10 parts 0.250 parts (THFMA) (MAA)3H-II 30 parts 60 parts -- 10 parts 0.5 parts (THFMA) (MAA)3I-II 30 parts 60 parts -- 10 parts 1 part (THFMA) (MAA)3J-II 30 parts 55 parts 15 parts 1 part -- (THFMA) (HPMA) (MAA)__________________________________________________________________________ .sup.1 Stereon 840A IBOMA isobornyl methacrylate OMA 2-ethylhexyl methacrylate ODA n-octylacrylate/n-decylacrylate mixture HDDA 1,6-hexanediol diacrylate HDDMA 1,6-hexanediol dimethacrylate THFMA tetrahydrofurfryl methacrylate HPMA 2-hydroxypropyl methacrylate MAA methacrylic acid CHP cumene hydroperoxide
Approximately equal portions of Parts I and II were applied to steel plates and allowed to cure at room temperature. The bonds were evaluated for tensile shear strength using ASTM standard method D1002-72 (1973) in pounds/inch 2 (psi) and for T-peel using ASTM standard method D1876-72 in pounds/linear inch (pli). These results are shown below (where, e.g., 3A is 3AI+3AII).
______________________________________Adhesive Sample No. Tensile Shear (psi) T-Peel (pli)______________________________________3A 2500 203B 1700 83C 2400 143D 2700 63E 2900 53F 1875 --3G 2600 --3H 2000 --3I 2600 --3J 1800 4______________________________________ | A two-part initiator system useful in acrylic adhesive compositions comprising in one-part a stable organoboron amine complex and in the second part an organic acid destabilizer or activator. This initiator is particularly useful in elastomeric acrylic adhesive compositions and provides a fast, room temperature cure with good stability and exhibiting both high tensile strength and high peel strength. | 2 |
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority of Taiwan Patent Application No. 102123932, filed on Jul. 4, 2013, the entirety of which is incorporated by reference herein.
BACKGROUND
[0002] 1. Technical Field
[0003] The disclosure relates to a tumor vessel embolizing agent, and in particular to a tumor vessel embolizing agent using nanoparticles.
[0004] 2. Description of the Related Art
[0005] A vessel tumor embolism of the head, neck and central nervous system has become an important treatment method in addition to a surgical operation. This embolism may decreases the rates of outbreak and death, and may assist to remove a portion of a tumor at the same time. For tumors which cannot be treated with a surgical operation, an embolism may be the main treatment method. The embolism is usually performed by vessel transportation. However, the embolus may also be directly injected into the tumor by penetration injection. The vessel transportation is usually performed by invasively penetrating a micro catheter into an artery (for example, the inguinal femoral artery, carotid artery, etc.) and then the micro catheter is led to the tumor to inject the embolus, embolizing the blood supply to the tumor. This embolus may be permanent or temporary. For example, this embolus may be liquid (ethanol, acrylic acid, Onyx) or particles (poly(vinyl alcohol), Gelfoam).
[0006] Gold nanoparticles (Au-NPs) have been used in a variety of nanotechnology applications, such as bio-sensing, biological imaging, and nanoscale treatment. Au-NPs play an important role in the biomedical fields such as health, diagnosis, and fighting malignant diseases such as cancer. Au-NPs are small in size and have Enhanced Permeability and Retention Effect (EPR) in tumor parts, and are able to selectively agglomerate in cancer tissues. Therefore, Au-NPs are suitable as drug-delivery carriers or radiotherapy enhancers.
[0007] It is desirable to provide a vessel embolizing agent which has specificity to a tumor and may block a tumor vessel to inhibit the growth of the tumor, and provide real-time monitoring as well.
SUMMARY
[0008] The present disclosure provides a tumor vessel embolizing agent, including: unmodified gold nanoparticles; and a pharmaceutically acceptable medium.
[0009] The present disclosure also provides a method of embolizing tumor vessel, including administrating gold nanoparticles as a tumor vessel embolizing agent into a subject to accumulate the gold nanoparticles at a tumor in the subject and to embolize a vessel of the tumor.
[0010] A detailed description is given in the following embodiments with reference to the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] The disclosure may be more fully understood by reading the subsequent detailed description and examples with references made to the accompanying drawings, wherein:
[0012] FIG. 1 is an X-ray image (exposure time: 100 milliseconds) of gold nanoparticles accumulated and embolized in a tumor vessel after arterially injecting the gold nanoparticles into mice, wherein the circular part is the scope of the tumor.
DETAILED DESCRIPTION
[0013] In the following detailed description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the disclosed embodiments. It will be apparent, however, that one or more embodiments may be practiced without these specific details.
[0014] The present disclosure utilizes unmodified gold nanoparticles as a tumor vessel embolizing agent and injects the unmodified gold nanoparticles into a tumor vessel in a subject. The subject is irradiated by an X-ray source to accumulate and embolize the gold nanoparticles with high absorption contrast at the tumor vessel. The X-ray image of the gold nanoparticles is then used to observe the tumor.
[0015] The X-ray source may be a synchrotron radiation X-ray source, a medical X-ray source, or a laboratory X-ray source. X-ray source has wavelength ranging from about 3.09×10 −1 to 6.1×10 −5 nm and energy ranging from about 4 keV-20 MeV. X-ray may overcome the inadequate penetration of photons in vivo, and is able to efficiently stimulate the nanoparticles administrated in the subject. In addition, X-ray source irradiation may be performed for less than about 1 second (60 minutes), preferably less than about 200 milliseconds (5 minutes). The effective penetration depth of the subject irradiated by the X-ray source may be about 30 cm from the surface to the deep tissue. Since the high-energy X-ray source adopted in the present disclosure has a high penetration ability in vivo, tumor cells in vivo may be monitored in real-time by X-ray imaging of the present disclosure, saving the need for sample slicing from living subjects as conventional medical imaging requires.
[0016] The present disclosure is suitable to embolize the tumor vessel in a subject. In one embodiment, subjects may be mammals, birds, amphibians, reptiles, fish, insects, or other appropriate multicellular animals.
[0017] In some embodiments, the tumor may include, but is not limited to, an epithelial tumor, brain tumor, melanoma tumor, lymphatic tumor, plasmacytoma, carneus tumor, ganglioglioma, thymic tumor, or a tumor in the oral cavity, esophagus, digestive system, respiratory system, bone, joint, soft tissue, skin, breast, reproductive system, urinary system, eye, eye socket, brain, other nervous system, endocrine system, lymph, bone marrow and etc.
[0018] In one embodiment, methods of administering the unmodified gold nanoparticles to a subject may include, but are not limited to, intravenous injection, arterial injection, lymphatic injection, or local organ injection. In one embodiment, the gold nanoparticles are injected into a tumor upstream artery.
[0019] The gold nanoparticles used herein are unmodified. In one embodiment, the gold nanoparticles in the present disclosure are grown by a synchrotron radiation method. This method may include providing gold ion-containing precursor solution such as HAuCl 4 .3H 2 O solution and adjusting the pH value of this precursor solution to make this precursor solution basic to prevent aggregation and size non-uniformity. For example, the pH value of the precursor solution may be adjusted to about 8-11. Then this precursor solution is irradiated by synchrotron radiation X-ray (such as 4-30 keV X-ray from a BL01A beamline) to transform the precursor into gold nanoparticles. The size of the gold nanoparticles may be adjusted according to the irradiation time. The longer the irradiation time, the smaller the size of the resulting gold nanoparticles. In some embodiments, the gold nanoparticles may range from 1 nm-100 μm, preferably from 1-50 nm. The gold nanoparticles are relatively inert, non-toxic and harmless to the subject.
[0020] In some embodiments, the gold nanoparticles may be combined with a pharmaceutically acceptable medium such as a solvent, dispersant or isotonic agent. In some embodiments, the pharmaceutically acceptable medium may include water, physiological saline, sugar, gel, porous matrix, preservative or a combination thereof. In some embodiments, the pharmaceutically acceptable medium is water. In one embodiment, the concentration of the gold nanoparticles may range from about 1-1000 mg/ml, preferably from about 1-300 mg/ml. For example, the concentration of the gold nanoparticles may be about 190 mg/ml. The injection dose of the gold nanoparticles may range from about 0.0001-100 g/kg, preferably from about 0.0001-2 g/kg. For example, the injection dose of the gold nanoparticles may be about 0.19 g/kg.
EXAMPLE
Example 1
In Vivo X-ray Image of Gold Nanoparticles Accumulated at Tumor Vessel
[0021] The mice used in this example were BALB/c mice (purchased from the National Laboratory Animal Center, Taiwan) approved by the Academia Sinica Institutional Animal Care and Utilization Committee (AS IACUC). All mice were housed in individual cages (five per cage) and kept at 24±2° C. with a humidity of 40%-70% and a 12-hour light/dark cycle.
[0022] 4-5 week-old mice were anesthetized by intramuscular injection of 10 μl of Zoletil 50 (50 mg/kg; Virbac Laboratories, Carros, France). A PE-08 catheter was inserted into a carotid artery of each of the mice (about 20-25 g of weight). Then 1000 μl, 50 mM of the above gold nanoparticle-containing contrast dye was injected into a late-stage tumor (16 days) in the mice from the carotid artery through the PE-08 catheter (PE-08 catheters, BB31695, Scientific Commodities, Inc., I.D.: 0.2 mm, O.D.: 0.36 mm). The injection rate of the contrast dye was 1 μl/s. During the development, the mice were kept under anesthesia using 1% isoflurene in oxygen. The image was an X-ray image taken 5 minutes after the injection of the mouse from its carotid artery. The exposure time was 100 milliseconds and the wavelength of the synchrotron radiation X-ray ranged from about 3.09×10 −1 -4.13×10 −2 nm nm. The energy of the synchrotron radiation X-ray ranged from about 4 keV-30 keV. The X-ray source had a dose of less than about 100 Gy. The result is shown in FIG. 1 , which is the X-ray image of the tumor vessel in the mice with the gold nanoparticles accumulated and embolized in the tumor vessel.
[0023] Although some embodiments of the present disclosure and their advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the disclosure as defined by the appended claims. For example, it will be readily understood by those skilled in the art that many of the features, functions, processes, and materials described herein may be varied while remaining within the scope of the present disclosure. Moreover, the scope of the present application is not intended to be limited to the particular embodiments of the process, machine, manufacture, composition of matter, means, methods and steps described in the specification. As one of ordinary skill in the art will readily appreciate from the disclosure of the present disclosure, processes, machines, manufacture, compositions of matter, means, methods, or steps, presently existing or later to be developed, that perform substantially the same function or achieve substantially the same result as the corresponding embodiments described herein may be utilized according to the present disclosure. Accordingly, the appended claims are intended to include within their scope such processes, machines, manufacture, compositions of matter, means, methods, or steps. | The present disclosure provides a tumor vessel embolizing agent, including: unmodified gold nanoparticles; and a pharmaceutically acceptable medium. The present disclosure also provides a method of embolizing tumor vessel, including administrating gold nanoparticles as a tumor vessel embolizing agent into a subject to accumulate the gold nanoparticles at a tumor in the subject and to embolize a vessel of the tumor. | 0 |
INTRODUCTION
Numerous stands have been provided for mounting cut trees, such as Christmas trees; however, these stands have not been without problems. For example, if the lower portion of the tree trunk is bent or bowed, often it is very difficult to mount the tree vertically. Or, if the tree is mounted vertically, it is only with a great amount of trial and error.
In the art, U.S. Pat. No. 4,156,323 discloses a tree supporting stand having a central support member mounting a plurality of radially extending legs, each of which is adapted to engage a horizontal surface for supporting a tree.
U.S. Pat. No. 3,231,227 discloses an adjustable tree support to make allowances for curvature in tree trunks and to actually hold tree trunks in a vertical position.
U.S. Pat. No. 3,779,493 discloses a stand for trees, particularly means to secure the tree in a water container to take various positions of inclination. A ball joint is provided to permit adjustment of the alignment of the water container relative to the base supporting the tree.
U.S. Pat. No. 4,699,347 discloses a a Christmas tree stand having a circular base and three legs extending upward in tripod form to an apex where a clamping mechanism is located. A ball is securely held between a claim base located atop one leg and a clamp top. An elongated member pivots on the socket leg, and the tree can be adjusted to the vertical position.
U.S. Pat. No. 4,571,882 discloses a tree stand which permits a tree, if deformed or if placed in the stand at an angle, to be aligned in a perpendicular position with respect to any type of floor, whether it be irregular or uneven. The receptacle for retaining the tree is formed integral therewith a hemispherical ball which is received by two adjustable jaws which form a hemispherical cavity.
The present invention overcomes the problems encountered in prior tree stands and permits mounting and securing the tree in a vertical position with ease.
SUMMARY OF THE INVENTION
Disclosed is an improved tree stand for holding a tree trunk to position a tree in a substantially vertical position. The tree stand is comprised of a base member having a clamp means positioned on the base member, a tree trunk holder having a sleeve for receiving the tree trunk. The sleeve has a circumferential band thereon which has a substantially circular outer surface. A clamp means is attached to the base member and is designed to receive the circumferential band and to permit the tree trunk holder to swivel prior to being clamped in position.
It is, therefore, an object of this invention to provide an improved tree stand.
It is yet another object of this invention to provide an improved tree stand having a tree trunk holder which permits ease of positioning a cut tree in the vertical position even when the tree trunk is bent or crooked.
Yet another object is to provide a tree stand having an adjustable tree trunk holder.
These and other objects of the invention will be understood from the following description and accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of the tree stand showing a tree trunk holder and base.
FIG. 2 is an elevational view of the tree trunk holder.
FIG. 3 is an elevational view of the base.
FIG. 4 is a cross-sectional view of the base and tree trunk holder showing water in the base.
FIG. 5 is a top view of the base along the line 5--5.
FIG. 6 is a top view of the tree trunk holder along the line 4--4.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1 is a perspective view of the tree stand 10 showing a circular base 12 having side wall 14 and collar 20. Collar 20 has a screw mechanism 24 which can be turned to clamp tightly around a tree trunk holder referred to generally as 30. Tree trunk holder 30 (FIGS. 2 and 6) comprises a sleeve-shaped portion 34 and has fasteners 32 for gripping the tree trunk upon its insertion into the sleeve-shaped portion. As can be seen in FIG. 2, sleeve-shaped portion 34 has a circumferential band 36 rigidly attached to sleeve-shaped portion 34. Band 36 is positioned on sleeve-shaped portion 34 to enable a part 38 of sleeve-shaped portion 34 to project into base 12 as seen in FIG. 4. In addition, sleeve-shaped portion 34 preferably has a part thereof which projects above band 36 to enable fastening of the trunk in the sleeve portion. Further, preferably sleeve portion has an end 40 which is tapered sufficiently inwardly to prevent the tree trunk from slipping through the sleeve portion. That is, tapered end 40 serves as a stop and prevents the tree trunk from resting on bottom 42 which would interfere with adjusting the tree into the vertical position, thereby defeating the purpose of the present invention.
Circumferential band 36 is generally circular and has an outer surface 44 which is curved or arched as shown. Preferably, surface 44 is curved to form a sector of a circle. As shown in FIG. 3, collar 20 has an interior surface 48 which is curved inwardly at lower section 50. That is, the inside diameter of collar 20 at lower extremity 50 is smaller than the inside diameter of collar 20 at upper extremity 51. The dimensions of band 36 should be such to permit the band to fit snugly in collar 20, as shown in FIG. 4. Surface 44 should be rounded or curved as noted to permit sleeve-shaped portion 34 to swivel or tilt from a vertical axis, as shown in FIG. 1, for example. Lower section 50 acts as a stop and as a bearing surface against band surface 44, thereby permitting sleeve-shaped portion 34 to be rotated when the tree trunk is inserted into the sleeve portion.
Collar 20 has a clamp means to secure band 36. The clamp shown is a screw mechanism 24 which serves to tighten collar 20 about circumferential band 36 whenever the tree has been placed in a desirable vertical position. Preferably, collar 20 is securely fastened at one point by welding, for example, so as to permit collar 20 to adjust and clamp band 36 firmly.
In using the adjustable stand, sleeve-shaped portion 34 may be removed from the base and the sleeve portion mounted on the tree trunk. The sleeve portion can be securely fastened to the trunk with screws 32 without the need for precisely centering the tree trunk within the sleeve portion. The sleeve portion containing the trunk is then placed in collar 20 and the tree rotated to a vertical position where it is then clamped using screw mechanism 24.
The adjustable tree stand has the added advantage that base 12 serves as a container for water 54 to keep the tree in fresh condition. An opening for adding water to the base may be provided in wall 14.
Further, the adjustable tree stand, including base and sleeve portion, can be fabricated or formed from plastic material, steel or aluminum, or like materials.
While the invention has been described with respect to embodiments and configurations shown in the drawings, it will be appreciated that other embodiments and configurations may be used which employ the spirit of the invention, and such is contemplated within the purview of the invention. | This invention relates to stands for cut trees, such as Christmas trees, and more particularly, it relates to a tree stand which permits the tree to be mounted vertically even when the tree trunk is bent. | 0 |
BACKGROUND OF THE INVENTION
This invention relates to a process, apparatus and system for removing radioactive radon gas, (radon-222) from potable water supplies, particularly for residential use.
Radon is a colorless, odorless, radioactive gas produced from the natural decay of uranium. In outdoor air, radon is diluted and not recognized as a health hazard. However, when radon gas is trapped indoors in air or water, in sufficiently high concentrations, it can be dangerous. Radon has been shown in several epidemiological studies to be a very potent carcinogen that causes lung cancer in humans. In A Citizen's Guide to Radon OPA-86-004 the United States Environmental Protection Agency (EPA) stated that scientists have estimated that about 5,000 to about 20,000 of the 130,000 lung cancer deaths in the United States in 1986 may have been caused by long term exposure to radon gas. Of these 5,000 to 20,000 deaths, about 500 to 1500 have been attributed to radon from residential potable water supplies. The risk from water borne radon may be higher than the combined risk from all of the other man-made chemical contaminants in residential drinking water.
The EPA is currently developing standards for acceptable levels of radon in public water supplies. The range of values for radioactivity concentration being considered run from 500 pico-curies per liter (pc/1) to 40,000 pc/1. Although the EPA standard for public water supplies may not be directly applicable to private residences, it is likely that the public will accept and regard this standard as the safe level.
Naturally occurring radon in water generally emanates from the radium in bedrock surrounding an underground well and through which the water going to the well flows. This is in sharp contrast to the most commonly known sources of contamination in water, which generally arise from remote point contamination sources such as leaky pipes or improperly disposed of waste materials. As such, methods of purifying water of organic contamination are not clearly applicable to removing radon from water.
There are fundamentally two known methods for treatment of water supplies for radon removal in the prior art: decay storage and spray aeration. Conceptually, the simplest example of decay storage is a large baffled water storage tank. Since radon has a radiological half life of only 3.785 days, simply holding the contaminated water in a storage tank for approximately a month will greatly reduce the radon level. One problem with this type of decay storage is that it requires a large tank which maintains essentially plug flow conditions to prevent backmixing.
Another example of decay storage requires accumulation of the radon on an adsorbent material such as activated carbon. Since the radon decays relatively rapidly, the concentration of radon on the adsorbent bed will initially increase, and then gradually reach an equilibrium with the influent radon concentration in the water. One disadvantage with this type of system is that the adsorbent bed gives off radioactivity as the radon decays, which may present a health hazard. A second disadvantage is that it is difficult to legally dispose of the radioactive carbon filter when it becomes fouled by other water borne contaminants such as iron, sediment or bacteria.
Spray aeration is the only method of aeration which is known in the prior art to be practical on a residential scale for removal of radon. For such spray aeration systems, radon removal efficiencies are reported to be approximately 50% on each spray cycle. Therefore, in order to achieve an overall removal efficiency of 90%, the water must be recycled through the spray aeration device 3 to 4 times. This is disadvantageous in that it requires a spray tank that is relatively large, to provide a sufficient quantity of treated water for use in the home.
In addition, aeration of water using an air stripping column is known in the prior art as a method of removing volatile organic contaminants (VOC) such as trichloroethylene, tetrachloroethylene, and benzene from water. Two general types of air-stripping aeration systems are known. In one type of system, an aeration column of at least fifteen to thirty feet in height is required to remove more than 90% of the organic contaminants in a single pass through the system. An aeration column of such a height is not considered practical for residential use. In the second type of system, a shorter aeration column may be used to remove more than 90% of the organic contaminants in the water, but only with multiple passes of the water through the system. In one such system, contaminated water is taken from an underground well and repeatedly pumped through the aeration system and back into the well. The purified water pumped into the well creates a progressively larger buffer zone against influent organic contamination, which would not be useful in inhibiting further radon contamination as the radon source surrounds the well. Any purified water that was injected back into the well would simply become recontaminated with radon which is a product of the decay of Radium, a naturally occurring element in the bedrock into which the well is drilled.
SUMMARY OF THE INVENTION
A general feature of the invention is a system which efficiently removes radon from water, in a single pass without recycling the water through the system, comprising a vertically oriented hollow column having mass transfer packing material, an inlet adapted for distributing radon laden water and an outlet adapted for venting radon gas in the upper portion of the column, a gas blower in fluid communication with the column, and at least one fluid container in fluid communication with the lower portion of the column.
In preferred embodiments, the system has a column which is sized to fit within a single story of a residential building, preferably being less than seven feet, six inches in height and having a substantially circular cross section with a diameter of less than one foot. There is also preferably a pump in fluid communication with the inlet, which in turn is in fluid communication with a well containing radon-contaminated water having a radioactivity concentration in excess of 10,000 pc/1 or the maximum contaminant level established by the EPA. Preferably also, the inlet is a course mist spray nozzle connected to the radon-contaminated well water for distributing the water evenly across the surface of the mass transfer packing. The gas blower is preferably located either near the bottom or near the top of the column to force air through the packed column to carry radon-laden air out of the building, with the fluid container being a tank of sufficient capacity to maintain a reservoir of treated water for immediate residential use either at the bottom of the column, or located remote from the column. Alternatively, there may be two fluid containers with a first fluid container at the bottom of the column, and a second fluid container remote from the column with a transfer pump in fluid communication with both fluid containers. In another preferred embodiment, the mass transfer material is packed to a height of less than six feet in the column, leaving a space between the nozzle and the mass transfer packing, upon a packing support screen.
Another general feature of the invention is a method of removing radon from radon laden potable water supplies comprising the steps of distributing the radon laden water in the upper portion of a vertically oriented hollow column containing mass transfer packing material, forcing air through the column to evaporate radon gas out of the radon laden water as the water splashes through the packing material, venting air laden with radon which has evaporated from the radon-laden water out of the column, and collecting water significantly purified by removal of radon (e.g. after removing on the order of 90% of the radon) as the water falls to the lower portion of the column, whereby the water so collected is suitable for use (e.g. bathing) without further removal of radon or further recycling of the processed water.
Preferred embodiments of the invention include positioning the column within a single story of a residential building, pumping the radon laden water from a well to the column, spraying the radon laden water upon the mass transfer packing material, blowing the air into the bottom of the column or drawing the air through the column, and pumping the collected water into a water container, whereby collected and stored water is available for immediate residential use (e.g. bathing).
The invention also provides a novel method of operation and automatic control sequence so that the pressure in the home water system is always maintained in a desired range.
Thus, the present invention provides an improved radon removal system for stripping potable residential water supplies of the radioactive gas radon 222, which is sized to fit within a residential structure, which continuously treats all of the water that the residential user demands and that the well can supply, which positively vents the stripped radon outside the home, and which reduces the radon concentration by at least 90% in a single pass through the equipment.
Other features and advantages of the invention will become apparent from the following description of the preferred embodiment and accompanying drawings, and from the claims.
DESCRIPTION OF THE PREFERRED EMBODIMENT
We first briefly describe the drawings.
FIG. 1 is a side elevation view with parts cut away of a radon removal system constructed in accordance with the preferred embodiment of the present invention;
FIG. 2 is a perspective view of packing material used in the system of FIG. 1; and
FIG. 3 is a side elevation view of a portion of an alternate embodiment of the system of FIG. 1.
Structure
Referring to FIG. 1, there is a radon removal system 10 in accordance with the present invention located within the basement of a residential building, resting on a concrete floor 12. The system 10 is of the type manufactured by North East Environmental Products, Inc. A supply pipe 14 passes through a concrete wall 16 and leads to a well pump (not shown) and a well which contains radon contaminated water (not shown). The opposite end of the pipe 14 leads to a spray nozzle 18 located at the top of a vertically oriented hollow column 20.
The hollow column 20 is preferably sized to fit within a single story of a residential building, and is typically less than seven feet, six inches in height. The column 20 preferably is fabricated from PVC duct material and has a diameter on the order of eight inches. The internal diameter of the column 20 is selected to provide a surface loading rate, at the well pump rate, of on the order of five to forty gallons per minute per square foot.
The column 20 contains polypropylene mass transfer packing material 22, which can be more clearly seen in FIG. 2. The packing material fills the column 20 to a height on the order of five feet, leaving a space between the top of the packing material and the spray nozzle 18. The packing material 22 preferably consists of either 5/8 inch or 1 inch Pall rings manufactured and sold by the Koch Company of Houston, Tex. Both of these sizes appear to perform equally well, however, the 1 inch size is currently most preferable, as it is less expensive per unit volume than the 5/8 inch size. The maximum nominal diameter of the packing material 22 is on the order of one-eighth of the internal diameter of the column 20. The preferred packing material 22 has a high surface to volume ratio, and consists of three linked open rings 24 and internal bracing members 26. Other commercially available mass transfer packings can also be used.
The column 20 is attached to an accumulator tank 28, preferably sized to contain on the order of 15 gallons of water. A float switch 30 within the tank 28 is connected to a transfer pump level control switch 32 which is in turn connected to a level control relay 34. The float switch 30 includes three distinct float switches, 30A, 30B and 30C. Switch 30B turns transfer pump 44 on, switch 30C turns transfer pump 44 off and switch 30A is a safety device which will be more fully described hereinafter.
An air blower 36, which preferably provides on the order of 20-40 cubic feet per minute of air, is located outside of the tank 28 for blowing air into the upper portion of the tank 28. As will be more fully set forth hereinafter, the blower 36 is controlled by a flow or pressure switch 40 located in the supply pipe 14 between the well pump and the spray nozzle 18. Alternatively, as shown in FIG. 3, the blower 36 could draw air out of the top of the column 20.
A transfer pipe 42, which has a check valve 43, connects the lower portion of the accumulator tank 28 to a transfer pump 44. The transfer pump 44 is preferably rated on the order of 1/3 horsepower providing on the order of 10 gallons per minute of water at 20 p.s.i. The pump 44 is controlled by a transfer pump pressure switch 46.
The transfer pump 44 is connected to a feed pipe 48. The feed pipe 48 feeds to a pressure tank 52. A pressure switch 54 is located at the top of the pressure tank 52, and a well pump control 56 is connected to the pressure switch 54. The well pump control 56 operates a well pump (not shown) located at the remote end of the supply pipe 14.
At the top of the hollow column 20, above the spray nozzle 18 is an air vent duct 58 containing a demister pad 60. The air vent duct 58 passes through a frame member 62 of the residential building and leads to the atmosphere.
Operation
Water contaminated with radon is pumped from the well (not shown) through the supply pipe 14 to the spray nozzle 18 at the top of the column 20. The radon laden water is sprayed from the nozzle 18 through the space above the packing material 22 onto the surface of the packing material. The water splashes through the packing material 22 and into the accumulator tank 28. Simultaneously, the air blower 36 blows air upward through the packing material 22 in the column 20.
The packing material 22 provides up to 10 equilibrium stages of contact between the falling water and rising air streams in the column 20. The blower 36 is preferably sized to provide an air to water flow rate ratio of between 5 to 1 and 100 to 1 cubic feet of air per cubic foot of water. The packing material 22 also serves to transfer oxygen into the water and to promote the oxidation of iron, which may be subsequently filtered or settled out of the water supply. Hydrogen sulfide, if present, is also substantially evaporated from the water. As is known from the prior art, packed column aeration systems will remove some portion of common volatile organic compounds from contaminated water supplies. The system of the present invention will probably remove less than 50% of the VOC'S
After the purified water collects in the accumulator tank 28, it is pumped by the transfer pump 44 through he transfer pipe 42 and the feed pipe 48 to the pressure tank 52, from where it can be delivered for use (e.g. bathing) anywhere within the residence.
Air which has been blown upward through the packing material 22 and has thus become contaminated with radon is vented through the vent duct 58 outside of the residence. The vent may be either through the sill plate of the house (in the same manner as a dryer vent) or preferably through a pipe running to a point above the roof line, similar to a sewer vent.
Control Logic
The water supplied for use in the home by the feed pipe 48 typically has a pressure on the order of 20 to 40 p.s.i., as is commonly found in most homes. When water is used in the home, the water level and pressure inside the pressure tank 52 drop. When the pressure drops below 20 p.s.i., pressure switch 54 activates well pump control 56 which operates the well pump (not shown), sending radon laden water into the supply pipe 14. As the water flowing in pipe 14 flows toward the column 20, it activates the flow or pressure switch 40 starting the blower 36.
As the system operates, water collects in the accumulator tank 28 causing the float 30 to rise to a point that activates the transfer pump level control switch 32, which operates the transfer pump 44 through the level control relay 34, causing the transfer pump 44 to pump water from the accumulator tank 28 into the pressure tank 52. As water is pumped into the tank 52, the pressure in the tank and the feed pipe 48 increases. Once the pressure reaches 40 p.s.i., pressure switch 46 is activated, shutting off transfer pump 44, and pressure switch 54 is simultaneously activated shutting off the well pump (not shown).
The transfer pump 44 is preferably sized to pump more water than the well pump (not shown) and therefore, even during periods of continuous water use, the transfer pump 44 is able to stay ahead of the well pump. After the well pump shuts off, flow or pressure switch 40 detects the lack of flow.
In the event of failure of level switch 30B, the water flow from the well could continue longer than necessary, flooding the basement. To prevent this, if rising water in the accumulator tank 28 reaches a sufficiently high point, (level switch 30A) the transfer pump level control switch 32 will operate the level control relay 34, turning on transfer pump 44.
Testing
The radon removal system of the present invention has been tested using radon contaminated well water. Preliminary tests showed that 85% of the radon content could be removed from radon laden water having initial radon concentrations of between 9,500 and 11,000 pc/1, using blowing air at 15° F.
Three prototype radon removal systems have been fabricated and installed in private residences for long term operational performance testing. Test results for these prototypes show that untreated well water having an initial radon concentration of on the order of 25,000 pc/1 could be purified by about 92%, well water having an initial radon concentration of on the order of 51,000 pc/1 could be purified by about 90%, and well water having an initial radon concentration of on the order of 102,000 pc/1 could also be purified by about 90%. | A radon removal system includes a packed mass transfer material aeration column and is sized to fit within a single story of a residential building. A residential water supply that is naturally contaminated with radioactive radon gas is connected to the top of the column. The water is preferably distributed across the top of the mass transfer packing by a coarse mist spray nozzle. The water splashes down through the packing and collects in a holding tank at the bottom of the column. Air, blown up through the column packing, comes into contact with the radon-laden water, and evaporates the radon out of the water. The radon-laden air is then vented outside the home. | 2 |
CROSS-REFERENCE TO RELATED APPLICATIONS
Not Applicable
FEDERALLY SPONSORED
Not Applicable
NAMES OF PARTIES TO JOINT RESEARCH AGREEMENT
Not Applicable
COMPACT DISC OR TEXT FILE (EFS-WEB)
Not Applicable
STATEMENT OF PRIOR DISCLOSURES
Not Applicable
BACKGROUND OF THE INVENTION
1.) Field of Invention
Hydrogen generator
2.) Description of Related Art
A) U.S. Pat. No. 899,403A; Date August, 1975, Cook, Jr., Edward H. B) U.S. Pat. No. 9,217,203, Date December, 2015, Gotheil-Yelle, Scott C) Published Ref.: “21 Years of Creative Work” by George Manojlovich, copyrighted 1977, pages 42-48 (Copy enclosed)
BRIEF SUMMARY
The Recycling Hydrogen Generator is a safety compliant, flexible combination of filters and compartments for removing sodium and chlorine from the electrolysis process of generating hydrogen from water by remixing or recycling the NaOH+HCl residue into NaCl+H 2 O for reuse as new recycled electrolyte, preventing dangerous chlorine gases from entering the atmosphere, and allowing for the safe generation of hydrogen for individual automobile and home use as a source of electricity.
The flexibility is extended by anodes and cathodes with larger surface area or by the connection of multiple insulated anodes to each other and multiple insulated cathodes connected to each other, wherein the rate of hydrogen production is controlled and the control is increased by an attached hydrogen storage tank, a pressure sensor, rheostat and cut-off switch to cut off the electricity causing the electrolysis. The addition of a breakable window between compartments C-1, C-3 and C-4 allows for the instant remix of NaOH+HCl+H 2 O residue with disproportionately created chlorine gas, in the event of a collision
The Recycling Hydrogen Generator combines and thereby improves upon various common knowledge technologies which have been patented already or discovered while working with the chlor-alkali process in order to solve problems such as preventing dangerous, disproportionately created chlorine gases from entering the atmosphere and controlling the production of only a safe amount of hydrogen.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
FIG. 1 : depicts the recycling hydrogen generator. Internal Side View of chlorine gas filtration system
FIG. 2 : depicts the recycling hydrogen generator Internal Side View of expanded surface anode and cathode in expanded compartment comprised of compartments labeled C-1, C-2 and C-3.
FIG. 3 : depicts the recycling hydrogen generator Top View of the expanded surface anode and cathode
FIG. 4 : depicts the recycling hydrogen generator Internal Side View of further expanded surface area comprising electrically connected, insulated wire mesh cylinders, where anodes are vented at one level and cathodes at a higher level.
FIG. 5 : depicts the recycling hydrogen generator Internal End View of alternating wire mesh anodes and cathodes with venting system.
DETAILED DESCRIPTION OF THE INVENTION
In FIG. 1 Internal Side View of chlorine gas filtration system shows the division of the approximately 12″×8″×12″ sturdy, acid-resistant plastic housing into five compartments labeled C#1-C#5. The Figure {it} shows in C#1 the anode used for electrolysis; a vent or digitally controlled, re-sealable opening on the upper side for the addition of more salt water, and a re-sealable tube adjacent to the anode for the extraction of chlorine gas into compartment C#4. Compartment C#1 is divided from compartment C#2 into substantially equal sections by a broken line representing the PEM (permeable ion-exchange membrane) or ion-selective membrane which allows hydrogen and oxygen atoms to pass through it (after electrolysis has split the NaCl molecules) but not the chlorine or sodium atoms or H 2 O molecules. A vent on the bottom of C#1 extends across the bottom of C#2, to allow the liquid remaining in both compartments, after electrolysis, to fall by gravity into compartment C#3. A breakable window on the left side of C#1 extends to the lower left side of C#3 for safety so that in case of accident, water and NaOH and HCl residue will mix with the dangerous chlorine gas contained in compartment C#4 immediately before any can enter the outside atmosphere due to damage to the outside housing or box, forming additional HCl, such as found in a normal car battery, which is much less dangerous than chlorine gas. FIG. 1 shows that compartment C#2 contains a cathode at the top with an adjacent closeable tube for the removal of hydrogen to a storage tank, and a vent for the addition of clean distilled water It shows that C#3 contains a vent on the lower left side for chlorine gas to be pumped from C#4 into the bottom of the solution in C#3 where the water or weak HCl serves as an additional filter (Filter 2) for the chlorine gases pumped into C#3, some of which will float to the surface, where a second vent above the solution level on the right side pumps any remaining chlorine gases created by disproportionality during electrolysis through a tube to the bottom of C#5 and a re-sealable vent on the bottom side which connects to the discharge or re-cycling tube for the liquid in C#3. FIG. 1 shows that compartment C#4 contains chlorine gas. It connects to the re-sealable chlorine gas tube adjacent to the anode in C#1. A vent on the bottom right internal wall allows the chlorine gas to be siphon pumped into the solution in C#3 to become HCl, and the breakable window that extends across the sides of both C#1 and C#3. Finally FIG. 1 shows that compartment C#5 has a vent and a tube from C#3 (above the solution level) to the bottom of C#5 where any remaining oxygen and chlorine gases can be filtered through a Na OH filter (Filter 3) and then 1a BaO 2 filter (Filter 4) before being released from the generator so that only oxygen is a byproduct
In FIGS. 2 and 3 , compartments C#4 and C#5 remain the same (although if C#3 also remains the same, the filtration system is improved), but the central combined compartment wherein C#1 and C#2 are combined by the elimination of the PEM and wherein this compartment can be expanded while C#3 is decreased in size has the addition of a very large surface zinc or zinc-plated or gold-plated (or half zinc-plated and half gold plated) titanium or steel anode (where zinc draws chlorine to it to form zinc-chloride, a solid which can be removed during maintenance cleaning while gold draws oxygen) and an equal size and shape rare metal or rare metal plated (preferably palladium which draws hydrogen) cathode. The zinc anode forms another filter (Filter 5) for removing chlorine gases, transforming them into less dangerous zinc-chloride.
FIG. 4 and FIG. 5 show an even larger surface anode and cathode system for a faster rate of hydrogen production comprising cylindrical or rectangular, zinc or gold plated wire mesh tubes as anodes and palladium-plated wire mesh tube cathodes, which are electrically connected anode to anode and cathode to cathode, but each individually insulated by a plastic wall sealed to the top of the said combined housing compartment C#1 and C#2 wherein this compartment can be expanded while C#3 is decreased in size, and wherein in the case of anodes the said insulating tube is sealed to the level 1 oxygen and chlorine vent and in the case of cathodes sealed to the level 2 hydrogen vent, but not touching the bottom of said combined housing compartment, where Na OH collects as a heavier molecule than hydrogen, oxygen or chlorine gas. There is a vent attached to the internal side wall of the said combined housing compartment to add fresh water. C#4 and C#5 remain the same, while C#3 is decreased in size or included in the said combined C#1 and C#2 retaining its vent above the liquid level entering compartment C#5, but a vent above each anode opens into a tube connected to C#4; while a vent above each cathode opens into a separate tube on a higher level for removal of hydrogen to a hydrogen storage tank. The said anodes and cathodes are spaced alternatively with anodes on one side of the said combined compartment and cathodes on the other so as to have access to the collection tube or vent level designated for them.
These variations in compartment, anode and cathode size in FIGS. 2, 3, 4 , and 5 cause varying rates of hydrogen production requiring for potential safety standard regulation an external hydrogen storage tank attached to the other end of the hydrogen collector tube from the cathode vent, equipped with a pressure sensor, rheostat, and electrical cut-off switch to stop hydrogen production when the tank is full. An external vibration system is attached to the said housing to improve remixing of the Na OH+H Cl residue into Na Cl+H 2 O; and is attached directly to the insulated palladium-plated cathode series to remove the hydrogen from the palladium cathode (Filter 6), which common knowledge in the industry has shown to be a problem especially in small enclosures which clog up easily, and is attached to the zinc-plated anode to remove the zinc-chloride from the zinc anode (Filter 5) unless this process is controlled manually or mechanically. | The recycling hydrogen generator comprises a chlorine filtration and safety feature system wherein alternative size and type housing compartments, anodes, cathodes and an attached vibration system recycle or remix electrolyte residue for use as new electrolyte and permit the free passage of hydrogen into the external storage tank with electric cut-off switch safety feature for control of the rate and amount of hydrogen produced for individual and home use, and wherein the breakable window safety feature instantly remixes said dangerous chlorine gases with said liquid electrolytic residue in case accident endangers the said housing. | 2 |
BACKGROUND OF THE INVENTION
The present invention relates to a surgical retractor holder, and more particularly, to a spring detent to keep the holder from coming off its support ring when the retractor is released.
In surgical operations on the chest or abdomen, it is customary to employ a retraction apparatus. Most, if not all, versions of the retraction apparatus are attached directly to the operating room table by means of affixation to a rail which is provided along each side of the table. By connection to one or both rails, the retraction apparatus generally provides a framework extending over the region of the patient in which the operation is to be performed. One or more retractor blades are attached to the apparatus framework, which may be a ring, and these blades are positioned in the incision and serve to hold back tissue, organs, and the like so that the surgeon may operate on the intended area. These retractors, known as self-retaining surgical retractors, contribute to the efficiency of the surgeon, and are generally sufficiently adjustable to be useful in a variety of such surgical operations. Typical variations of this type of retractor are found in U.S. Pat. Nos. 3,572,236 2,594,086 and 2,586,488. Although the known and available self-retaining surgical retractors offer many advantages in the operating room, some deficiencies are evident as well.
Retractor blades usually include a long handle which engages a holder. The holder mounts on the apparatus framework or ring. Many holders are attached to the ring by means of a set screw or other means. Moving the holder requires unscrewing the set screw, moving the retractor and then tightening the screw. It would be desirable to have a holder which eliminated the loosening and tightening of a set screw but at the same time was securely fastened to the ring.
SUMMARY OF THE INVENTION
Surgical retractor assemblies include a support post which clamps to the operating table. An extension rod is adjustably connected to the post and is adapted to extend in a direction generally over a patient on the operating table. The extension rod clamps to a generally oval-shaped ring. At least one retractor blade is connected to the ring by a holder.
Preferably, a plurality of retractor blades are mounted on the ring member by separate holders, with each blade being adjustable both in its position along the ring member and in a general radial direction toward the open center of the ring member.
Each holder includes a quick-release ratchet mechanism which attaches the retractor blades to the ring member. The holder has an open slot for receiving the ring and a spring detent whose end closest to the ring center is enlarged to snap around the ring and keep the holder engaged in the ring when the retraction is relaxed. The spring detent only loosely retains the holder so that the holder may be easily moved along the ring. No wing nuts or screws are required in this invention in order to make the attachment of retractor blade to the ring member.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view illustrating the preferred surgical retractor assembly attached to a surgical operating table and ready for use in a surgical operation on a patient.
FIG. 2 is a top plan view of one retractor blade attached to the ring member, shown in partial view; and,
FIG. 3 is an enlarged perspective view of the preferred pawl mechanism for attaching the retractor blade to the ring member.
DETAILED DESCRIPTION
While this invention is satisfied by embodiments in many different forms, there is shown in the drawings, and will herein be described in detail, a preferred embodiment of the invention with the understanding that the present disclosure is to be considered as exemplary of the principles of the invention and is not intended to limit the invention to the embodiment illustrated. The scope of the invention will be pointed out in the appended claims.
Adverting to the drawings, particularly to FIG. 1, there is illustrated a self-retaining surgical retractor assembly 10 attached to a surgical operating room table 12 and in a position as it would appear during an operation on a simulated patient P. The main components comprising this surgical retractor are an elongated support post 14, an elongate extension rod 15 which is connected to support post 14 by a coupling device 16, a substantially flat, oval-shaped ring member 18 adjustably affixed to extension rod 15 and a plurality of retractor blades 19 adjustably mounted on ring member 18.
In FIGS. 2 and 3, one retractor blade 19 is shown mounted on ring member 18 with its quick-release pawl attachment mechanism with body section 72. The retractor blade includes the blade portion 74 which is inserted into an incision for restraining tissue, organs and the like during the surgical procedure. A handle 75 extends from blade portion 74 and, in the embodiment being described, preferably has a square or rectangular cross-section. Along one surface of handle 75 is a plurality of spaced ratchet teeth 76 which are spaced to provide small incremental adjustments of the handle. Handle 75 is inserted through a compatible opening bore 78 extending through body section 72, as seen in FIG. 3. Teeth 76 on the handle face a spring-loaded pawl 79 which is connected by a pivot pin 80 to the pawl mechanism. The leading edge 81 of pawl 79 mates with teeth 76 and thereby locks the handle in a fixed position. The mechanism is slid onto ring member 18 by means of a slot 82 through the body 95 of the pawl mechanism. Slot 82 is open to the opposite surface from that surface which leading edge 81 of the pawl extends. Although not seen in FIG. 3, slot 82 may incorporate a dowel or other pin with a smooth radius to matingly fit into an indentation 70 on ring member 18, to hold the pawl mechanism securely onto the ring member. By referring to FIG. 2, it can be seen that body section 72 holds retractor blade 19 so that the handle extends in a generally radial direction and is thus adjustable in the radial direction by means of pawl 79 and ratchet teeth 76. It is appreciated that the pawl mechanism requires no screws, wing nuts, or other fixation devices inasmuch as the inwardly directed radial force transmitted from blade portion 74 during use of the retractor tends to maintain the pawl mechanism in position on ring member 18. This type of pawl mechanism mounting with the various retractors can be seen by referring to FIG. 1, which shows retractor blades 19 in a position as they may appear during a surgical operation on a patient P. It can be seen that each retractor may be adjustably positioned to any desirable annular position on ring member 18; also, each retractor blade may be adjusted in a generally radial direction toward or away from the open center of the ring member. A spring detent 90 is attached to the bottom of body section 72 by means of screws 92. The front end of detent 90 curls up to a height slightly higher than the top surface 94 of slot 82. The radial distance between the inside surface 96 of slot 82 and the confronting surface 98 of spring detent 90 is somewhat longer than the width of annular ring 18 so that the pawl mechanism will stay loosely engaged on ring 18 when the retraction is relaxed without impeding the motion of the holder of along ring 18. | A quick-release ratcheting holder for a surgical retractor which includes a spring detent to keep the holder from coming off the ring member when the retractor is relaxed. | 0 |
RELATION TO OTHER APPLICATIONS
[0001] The present application claims benefit of U.S. Provisional Application No. 62/098,170 filed Dec. 30, 2014.
FIELD OF THE INVENTION
[0002] The present invention relates to garments in general, and, more particularly, to fire-retardant or flame-resistant garments.
BACKGROUND OF THE INVENTION
[0003] Fire-retardant, flame-retardant, or flame-resistant (collectively “FR”) garments are in use across many industries. Any user that deals with high temperatures, potential fires, heated metal, explosives, or any other combustible, flammable, or explosive matter is a potential wearer of fire-retardant garments.
[0004] The market for fire-retardant garments includes workers in the oil and gas fields, firefighters, welders, metallurgists, workers on high-voltage electrical cables, etc. In recent years, this market has expanded in response to the War on Terror. With increased use of incendiary devices and improvised explosive devices, the market has expanded beyond explosive ordnance disposal (EOD) personnel. Now any soldier, sailor, airman, or marine may be exposed to explosives or incendiary devices. Contractors and civilian personnel that serve in these capacities may also be exposed.
[0005] Typically, most fire-retardant garments mimic those of regular garments. For example, a firefighter's pants and coat, a welder's apron, or a soldier's uniform. There are limitations to using the existing clothing model when applied to fire-retardant garments.
[0006] One such limitation is in the use of fasteners. Many types of fasteners are simply insufficient. Regular buttons and almost all plastic fasteners melt. Metal fasteners or plastic fasteners that can withstand high heat can get too hot and can burn a wearer when exposed to a wearer's skin. Clothes worn under the garment can be burnt or melted, exposing a wearer to further danger.
[0007] There exists a need for improved fire-retardant garments.
SUMMARY OF THE INVENTION
[0008] The present invention is a fire-retardant garment that combines a new fastener with improved fastener placement to prevent exposure of a wearer's skin or clothes to the fastener itself without some of the disadvantages of the prior art. This provides superior fire-retardant qualities and protection for a wearer.
[0009] For the purpose of this specification, the term “garment” is defined as any clothing that can be worn by a person or animal or placed upon some other apparatus or item so that the wearer may be protected from the elements or other dangers, such as fire or dangerous materials.
[0010] In accordance with the illustrative embodiment of the present invention, fire-retardant garment 200 is a garment with improved fasteners and improved placement of the fasteners. Fire-retardant garment 200 comprises improved fasteners that combine both the fastener and the length adjuster in order to prevent the metal or other material from the length adjuster from coming into contact with a wearer's skin or clothes. Furthermore, the placement of the fastener and the fastening point lower on the garment has the benefit of keeping metal parts or other dangerous parts away from the wearer's skin or clothes.
[0011] It will also be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention in which the fire-retardant garment is fashioned in a different manner.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] FIG. 1 depicts a fire-retardant garment in accordance with the prior art.
[0013] FIG. 2 depicts a fire-retardant garment in accordance with the illustrative embodiment of the present invention.
[0014] FIG. 3 depicts a fastener and fastening point in accordance with the illustrative embodiment of the present invention.
[0015] FIG. 4 depicts a fastener in accordance with the illustrative embodiment of the present invention.
DETAILED DESCRIPTION
[0016] FIG. 1 depicts a fire-retardant garment in accordance with the prior art. Fire-retardant garment 100 is comprised of two (2) length adjusters 101 , two (2) fasteners 102 , two (2) fastening points 103 , two (2) straps 104 , and one (1) central pocket 105 . Fire-retardant garment 100 is also in the form of overalls.
[0017] Fire-retardant garment 100 is in the form of overalls, which provides protection to a wearer's legs and torso.
[0018] FIG. 2 depicts a fire-retardant garment in accordance with the illustrative embodiment of the present invention. Fire-retardant garment 200 is comprised of two (2) length adjusters 201 , two (2) fasteners 202 , two (2) fastening points 203 , two (2) straps 204 , and one (1) central pocket.
[0019] Although fire-retardant garment 200 comprises two (2) fasteners, it will be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention in which there are any number of fasteners.
[0020] Although fire-retardant garment 200 comprises two (2) fastening points, it will be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention in which there are any number of fastening points.
[0021] Although fire-retardant garment 200 comprises two (2) length adjusters, it will be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention in which there are any number of length adjusters.
[0022] Although fire-retardant garment 200 comprises two (2) straps, it will be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention in which there are any number of straps.
[0023] Although fire-retardant garment 200 comprises one (1) central pocket, it will be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention in which there are any number of pockets.
[0024] Although fire-retardant garment 200 is in the form of overalls, it will be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention in which fire-retardant garment 200 takes any form, for example and without limitation: trousers, a jacket, an apron, etc.
[0025] Fire-retardant garment 200 is a garment comprised of one or more fire-retardant materials or textiles sewn together such that they provide a wearer with protection from fire, heat, and other dangerous elements. These types of materials are known to those skilled in the art. It will be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention in which the materials or textiles used are any material or textile.
[0026] For the purpose of this specification, the term “textile” is defined as any flexible material that consists of a network of fibers, whether woven or non-woven, include any cloth or fabric, such that said textile may be used in production of further goods, for example and without limitation: a garment. For example and without limitation, textiles would include, yarns, felt, nylon, etc.
[0027] In accordance with the illustrative embodiment of the present invention, the textile used would be a fire-retardant, flame-retardant, or flame-resistant (FR) material. However, it will be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention in which any material is used.
[0028] In accordance with the illustrative embodiment of the present invention, fire-retardant garment 200 is sewn in the shape of overalls. This type of garment provides the wearer with protection for the wearer's legs and torso. However, it will be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention in which another garment type is used, for example, and without limitation: trousers, jacket, etc.
[0029] Fire-retardant garment 200 has fasteners and fastener points that are different from fire-retardant garment 100 .
[0030] In accordance with the illustrative embodiment of the present invention, straps 204 attach to the bib portion of the garment (which covers the wearer's chest) using a rivet (fastening point 203 ) and clasp mechanism (fastener 202 ). However, it will be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention in which another fastener is used, for example and without limitation: snaps, a hook mechanism, hook-and-loop fastener, etc.
[0031] A disadvantage of the prior art is in the placement of fastener 102 and fastening point 103 in fire-retardant garment 100 . Portions of the fastener are exposed to a wearer's skin at the point above the bib portion of the garment. In contrast, the lower placement of the points allows for additional protection for the wearer of fire-retardant garment 200 .
[0032] In contrast with fire-retardant garment 100 , the fastener 202 and fastening point 203 are placed lower on the garment of fire-retardant garment 200 . One advantage of this placement is that all portions of the fastener and fastening points are protected from the wearer's skin by the fire-retardant material.
[0033] Fastening point 203 is at a lower point on fire-retardant garment 200 than that of fastening point 103 on garment 100 . In accordance with the illustrative embodiment of the present invention, fastening point 203 is approximately 1 inch (1″) lower than the placement of fastening point 103 in the garment of FIG. 1 . It will be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention in which the placement of fastening point 203 is at a point different than the one illustrated. For example, and without limitation: at a still lower point, like 2 inches (2″) below that or fastening point 103 , or at any point.
[0034] Furthermore, it will be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention in which the placement of fastening point 203 may depend on other factors, for example, and without limitation: the size of the rivet, the size of the clasp, the size of the length adjustors, the materials used in the garment, etc.
[0035] However, it will be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention, in which a different attachment mechanism is used, a different placement is chosen, etc.
[0036] In accordance with the illustrative embodiment of the present invention, the length adjuster of fire-retardant garment 200 , which adjusts the length of the straps, is attached to the fastener. In contrast, the length adjuster of fire-retardant garment 100 is placed on the strap itself.
[0037] FIG. 3 depicts a fastener and fastening point in accordance with the illustrative embodiment of the present invention. FIG. 3 is comprised of length adjuster 201 , fastener 202 , and fastening point 203 .
[0038] Although the closure depicted in FIG. 3 is a rivet and clasp typical of overalls, it will be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention in which a different closure is depicted, for example and without limitation: snaps, a clasp, hook-and-loop fastener, etc.
[0039] Although the length adjuster 201 , fastener 202 , and fastening point 203 are depicted as being comprised of metal or a metallic substance, it will be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention in which a different substance is utilized, for example and without limitation: plastic, fiber, etc.
[0040] Although the closure depicted in FIG. 3 comprises both the closure and a length adjuster as a single unit, it will be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention in which these are separated.
[0041] Although the closure depicted in FIG. 3 comprises both the closure with a length adjuster directly above it, it will be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention in which the closure and length adjuster are attached in a manner differently than that displayed.
[0042] As described, infra, with respect to FIG. 2 , the fastener and fastening point illustrated in FIG. 3 provide advantages over the prior art.
[0043] The closure depicted in FIG. 3 has both fastener and length adjuster on the same piece. This provides several advantages over the prior art.
[0044] In the prior art, as in FIG. 1 and fire-retardant garment 100 , the length adjuster was separated from the fastener. This placed the length adjuster along the strap of the garment. In this situation, the metal or other material would come in contact with the clothes under the fire-retardant garment or directly in contact with a wearer's skin. This presents a significant safety risk. By placing the lengthener with the fastener, this effect is lessened. The illustrative embodiment of the present invention thus increases safety for the wearer.
[0045] Another advantage of combining the fastener with the length adjuster is that it may be formed form a single mold, which may have cost savings over the separate pieces used in the prior art implementations.
[0046] In the prior art, such as fire-retardant garment 100 , the fastener and fastening points are placed at the top of the bib portion of the garment. In this situation, the metal or other material of the fastener would come in contact with the clothes under the fire-retardant garment or directly in contact with a wearer's skin. This presents a significant safety risk.
[0047] In the illustrative embodiment of the present invention, fire-retardant garment 200 , discussed, infra, with respect to FIG. 2 , the placement of the fastener and the fastening points are moved so that the metal (or other material) does not come into contact with the clothes under fire-retardant garment 200 or with a wearer's skin.
[0048] It will be clear to one skilled in the art, after reading this disclosure, how to make and use the illustrative embodiment and alternative embodiments of the fastener and length adjuster illustrated in FIG. 3 .
[0049] FIG. 4 depicts a fastener in accordance with the illustrative embodiment of the present invention. FIG. 4 is comprised of fasteners 401 and fasteners 402 .
[0050] Although fire-retardant garment 200 comprises two (2) hook-and-loop fastener pairs, it will be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention in which there are any number of hook-and-loop fasteners.
[0051] Although fire-retardant garment 200 comprises hook-and-loop fasteners, it will be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention in which a different fastener is used, for example, and without limitation: snaps, a clasp, rivets, etc.
[0052] In accordance with the illustrative embodiment of the present invention, the length adjuster of FIG. 3 is attached to the fastener. One issue that may arise when combining these two pieces is that a length of excess material may materialize. Thus, FIG. 4 incorporates a fastener 401 and fastener 402 that fastens any excess material to the strap of the garment. This has the advantage of keeping any excess material from getting in the way of a wearer or getting caught on something, potentially exposing the wearer to other dangers.
[0053] In accordance with the illustrative embodiment of the present invention, the fastener is hook-and-loop fastener, more commonly known by the brand name as “VELCRO.” However, it will be clear to one skilled in the art, after reading this disclosure, how to make and use alternative embodiments of the present invention in which other fasteners are uses, for example and without limitation: snaps, a belt buckle, 3M Command, 3M Dual Lock, other hook-and-loop-style fasteners, VELCRO or VELCRO-like attachments, etc.
[0054] In accordance with the illustrative embodiment of the present invention, the fastener is placed on the excess material and on the strap such that all parts of the fastener are contained by the fire-retardant fabric. In other words, fastener 401 and fastener 402 are of widths less than the width of the straps to which they are attached. Alternatively, this may be viewed as the fasteners are placed on the excess material and on the strap such that no part of fastener 401 and fastener 402 may be exposed to a wearer's clothing or skin.
[0055] It will be clear to one skilled in the art, after reading this disclosure, how to make and use other implementations of the present invention in which one or more of the parts are omitted or are utilized in a different manner than the one presented.
[0056] It is to be understood that the disclosure teaches just one example of the illustrative embodiment and that many variations of the invention can easily be devised by those skilled in the art after reading this disclosure and that the scope of the present invention is to be determined by the following claims. | A fire-retardant garment that combines a new fastener with improved fastener placement to prevent exposure of a wearer's skin or clothes to the fastener itself without some of the disadvantages of the prior art is disclosed.
In accordance with the illustrative embodiment of the present invention, the fire-retardant garment has improved fasteners and improved placement of the fasteners. The fire-retardant garment comprises improved fasteners that combine both the fastener and the length adjuster in order to prevent the metal or other material from the length adjuster from coming into contact with a wearer's skin or clothes. Furthermore, the placement of the fastener and the fastening point lower on the garment has the benefit of keeping metal parts or other dangerous parts away from the wearer's skin or clothes. | 0 |
BACKGROUND OF THE INVENTION
The present invention relates generally to safety ski bindings, and more particularly to a heel unit for a safety ski binding which permits automatic release of the ski boot upon application of a predetermined minimal separation force and also has automatic step-in capabilities permitting locking of the ski boot sole without manual intervention.
In known ski bindings of this kind, such as the one described in French Pat. No. 1,572,250, an elastic locking means is provided laterally between a sole catch and the side branches of a stirrup. The locking means comprises tumblers pivoted on the sole catch on horizontal axes, a part of the tumblers being subjected to a spring, while another part cooperates with the side branches of the stirrup. Such known ski binding is relatively complex, which does not enable it to be as small as desirable. Furthermore, such a binding must be reclosed manually around the sole of the boot.
The ski binding, according to the invention, avoids the disadvantages of the prior art. Though having a structure simpler than that of the prior art, it affords the same safety on release in case the skier falls and, furthermore, enables the skier to put on his binding automatically, without manual intervention, by simply stepping into the binding mechanism.
SUMMARY OF THE INVENTION
In accordance with the present invention, a binding comprises a sole catch, a first part of which is designed to lock the end of a boot sole placed on a support, and a second part capable of pivoting on a bridge arranged transverse to the support and parallel to the bearing plane of the latter on the sole; the bridge being the transverse portion of a stirrup having two legs bent in relation to the bridge and connected, by their opposite ends, to the two sides of the support respectively adjacent the sides of the end of the boot sole; elastic locking means are provided laterally between the sole catch and the legs, whereby rotation of the sole catch around the bridge is possible only when a predetermined minimum effort is exerted upwardly by the edge of the sole on the first part of the sole catch.
The locking means consist, on each side of the sole catch, of a ramp integral with the latter, working together with the adjacent leg of the stirrup. Each leg is elastically deformable laterally under the action of the ramp only when a predetermined minimum effort is exerted upwardly by the edge of the sole on the first part of the sole catch. A stop is placed on each side of the sole catch and works together with the adjacent stirrup leg to prevent the downward rotation of the sole catch around the bridge. The two stirrup legs are also elastically deformable in a plane parallel to the longitudinal axis of the support and perpendicular to the bearing plane of the latter. Means are provided to keep the sole catch a predetermined distance above the support so as to enable the ski binding to be locked on the boot automatically. Without departing from the scope of this invention, a single ramp, placed on one side of the sole catch, and a single stop, whether placed on the same side or not, can each work together with a single leg of the stirrup; the ramp or ramps, as the case may be, can be adjustable in position, for example, by lateral sliding in relation to the sole catch.
In some embodiments, in which the legs are pivotally mounted on the support, the means for keeping the sole catch a predetermined distance above the support consist of at least one stop integral with at least one leg of the stirrup, capable of working together with the support or with the ski. This stop can, for example, consist of a bent intermediate part of one of the legs of the stirrup. It can also consist of a part of said leg placed between said bent part and the pivot point of the leg on the support.
In other embodiments, the means for keeping the sole catch a predetermined distance above the support consist of a device preventing the pivoting of the legs at their point of connection with the support; for example, the legs can be firmly fastened to the support; they can also be detachable, but shaped to be adjusted in the support so as not to be able to turn in relation to said support.
In other embodiments, each leg of the stirrup contains a wound intermediate part forming at least one turn, one part of which works together with the corresponding ramp. That turn can, for example, when the stirrup is in skiing position, be placed roughly over the rest of the leg; its part roughly farthest from the rest of the leg works together with the ramp; the part roughly diametrically opposite the turn can advantageously constitute the bent part serving as a stop to keep the sole catch a predetermined distance above the support.
There has thus been outlined rather broadly the more important features of the invention in order that the detailed description thereof that follows may be better understood, and in order that the present contribution to the art may be better appreciated. There are, of course, additional features of the invention that will be described hereinafter and which will form the subject of the claims appended hereto. Those skilled in the art will appreciate that the conception upon which this disclosure is based may readily be utilized as a basis for the designing of other structures or methods for carrying out the several purposes of the invention. It is important, therefore, that the claims be regarded as including such equivalent constructions and methods as do not depart from the spirit and scope of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
Certain specific embodiments of the invention have been chosen for purposes of illustration and description, and are shown in the accompanying drawings, forming a part of the specification wherein:
FIG. 1 is a side view of a first embodiment of the invention, in skiing position;
FIG. 2 is a side view of the same embodiment as FIG. 1, illustrating engagement;
FIG. 3 is a side view of the same embodiment as FIG. 1, illustrating release;
FIG. 4 is a plan view of the first embodiment of the invention;
FIG. 5 is a sectional view taken along lines V--V of FIG. 4; and
FIG. 6 is a perspective view of a second embodiment of the invention.
DESCRIPTION OF THE INVENTION
With reference to FIGS. 1 to 4, the ski safety binding comprises a sole catch 1, a first part of which is provided to engage and lock the end of a sole 2 of a boot in order to keep the latter on a support 3. The first part has two rollers 4 and 5 arranged to be placed respectively on each side of sole 2; the rollers being cone-shaped in order to match the shape of sole 2. The rollers are pivoted on a shaft 6, placed parallel to the upper face of the support and transverse to the longitudinal axis of the latter, supported by sole catch 1. As illustrated, support 3 consists of a sole plate itself forming part of a safety device wherein sole catch 1 constitutes a second safety feature which is capable of being released only after release of the first safety device. The second safety feature is important, notably, when the first safety device contains a foot plate which is connected to ski 9, even after release, by a flexible cable subjected, for example, to the action of an elastic tension device. Without departing from the scope of this invention, support 3 could consist of ski 9 itself, sole catch 1 constituting in that case the only safety release device.
Sole catch 1 is pivoted by a second part, farther from the end of sole 1 than the first, on a bridge 7 of a stirrup 8. Bridge 7 is arranged parallel to shaft 6, transverse to support 3, and is connected to support 3 by legs 11 and 12 having inwardly turned feet pivotally supported within openings 13 provided respectively on each side of support 3. Legs 11 and 12 are bent at 14 to assume a rough S-shape; one of their parts 15, close to bent part 14, is provided to bear on a stop 16 integral with each side of support 3. A second part 17 maintains sole catch 1 a specific distance upwardly from support 3 and from the ski.
A locking device is laterally provided between sole catch 1 and legs 11 and 12. It consists, first of all, of a ramp 21 placed on each side of sole catch 1; each ramp 21 works together with the top part 18 of the corresponding leg 11 or 12, which is elastically deformable laterally in the direction of arrows 22 and 23 (FIG. 4). Each ramp 21 is situated, when the binding is in skiing position (FIG. 1), below the corresponding leg 11 or 12, and is oriented in the direction of the latter. Preferably, ramps 21 are mounted on sole catch 1 so as to be adjustable in the direction of arrows 22 or 23 crosswise to sole catch 1. As represented in FIG. 5, an adjusting screw 24 has, for that purpose, a cone-shaped end 25 which engages two other ramps 26 provided at one end of two sliding elements 28 and 29 that in turn have ramps 21 at their other end. Thus, the axial displacement of screw 24 in the direction of arrow 30 separates elements 28 and 29, in the direction of arrow 22 and 23 respectively, to adjust the position of the two ramps 21 to the exact spacing of legs 11 and 12. Sliding elements 28 and 29 contain oblong openings 31 through which pass fastening screws 32, the threaded end of which is engaged with threaded openings provided in a plate 33. The locking of screws 32 immobilizes sliding elements 28 and 29 between sole catch 1 proper and plate 33.
Sole catch 1 further includes, on each of its side parts, a stop 37 working together with the corresponding leg 11 or 12 in order to prevent the rotation of sole catch 1 around bridge 7, downwardly in the direction of arrow 38 (FIGS. 1 and 2). Finally, dished area 39 is provided at the top of sole catch 1 (FIGS. 1 and 4), the purpose of which will be described hereinafter.
Legs 11 and 12 are also elastically deformable in the direction of arrow 40 (FIGS. 1 and 2), in a plane parallel to the longitudinal axis of support 3 and perpendicular to the bearing plane of sole 2 on the latter.
To lock into the binding, the end of the sole of boot 2 is brought into contact with rollers 4 and 5 and then, as represented on FIG. 2, the sole is shifted in the direction of arrow 41, which produces an elastic deformation of the legs 11 and 12 and a rotation, in the direction of arrow 40 of bridge 7 about an axis defined by stops 16. At the same time, rollers 4 and 5 are temporarily separated from sole 2. When sole 2 is borne on support 3, legs 11 and 12 elastically resume their rest position, rollers 4 and 5 then being lodged on the upper edge of sole 2, as represented in FIG. 1. The safety binding is thus in skiing position. If packed snow, for example, gets in between sole 2 and support 3, the binding is put on in the same way, but in this case a slight play exists, after putting it on, between stops 16 and parts 15 of legs 11 and 12 which does not hamper the binding capabilities.
In the event the skier falls, when a predetermined minimum separation effort is exerted, upwardly, for example, in the direction of arrow 42, between the edge of sole 2 and support 3, ramps 21 push back laterally, in the direction of arrows 22 and 23 respectively (FIG. 4), legs 11 and 12, which are thus elastically deformed, permitting rotation, in the direction of arrow 43, of sole catch 1 around bridge 7 of stirrup 8. As represented in FIG. 3, rollers 4 and 5 thus free sole 2 of the boot. As can be seen in FIG. 3, this release occurs only when support 3 has by itself already separated from the ski and a flexible cable 44, joining the latter to the ski, has reached the limit of extension. The release of sole catch 1 would take place in the same way if support 3 consisted of ski 9 itself.
To take off the binding at will, it is necessary only to exert in the direction of arrow 46 an effort on sole catch 1 with, for example, a ski pole inserted in dished part 39 (FIG. 1); legs 11 and 12 thus yield in the direction of arrow 40 and the edge of sole 2 is released.
When not skiing, legs 11 and 12 may be rotated, in the direction of arrow 45 (FIG. 1), from the position where they are bearing on stops 16 and are advantageously flattened, together with sole catch 1, against support 3. Sole catch 1 is thus reduced in size, more favorable for carrying the skis.
According to a variant of the first embodiment, not represented in the drawing, bent parts 14 and stops 16 are eliminated and legs 11 and 12, instead of being hinged at 13 in support 3, are secured at 13 in said support 3 so that they cannot turn in relation to the latter. All of the other elements are identical to those of the first embodiment previously described. The operation of the unit is likewise similar.
In a second embodiment of the invention, illustrated in FIG. 6, the S-shaped legs 11 and 12 of the first embodiment are replaced by legs 51 and 52, each of which contains an intermediate part forming a turn 53. Ramps 21 of FIGS. 1 to 5 are replaced by cone-shaped ramps 54. When stirrup 8 is in skiing position, each turn 53 is set roughly over the rest of the corresponding leg 51 or 52. The top area 55 of the leg works together with the corresponding cone-shaped ramp 54 (FIG. 6). An area 56 of each turn 53, roughly opposite area 55, is provided to serve as a stop during skiing in order to keep sole catch 1 a predetermined distance above support 3 and thus enable the ski binding to be put on automatically. All of the other elements and operation are identical to those of the first embodiment. The presence of turns 53 favors the elastic deformation of legs 51 and 52 laterally in the direction of arrows 22 or 23 as well as longitudinally in the direction of arrow 40.
The ski safety binding, object of the invention, can be used in all cases where such a binding must have a very small volume, while easily enabling it to be put on automatically. While represented herein as a heel unit, the invention may also conceivably be used as a toe binding. | A step-in safety ski binding comprises a stirrup mounted to a support, a boot clasp is rotatably mounted to the stirrup and includes a first part which engages the ski boot sole and a second part which pivots on the bridging section of the stirrup. An elastic locking mechanism is provided laterally between the sole engaging part and the stirrup legs so that the boot sole can be automatically locked therein and is releasable therefrom upon application of a predetermined minimum separation force. | 0 |
BACKGROUND OF THE INVENTION
[0001] 1. Field of Invention
[0002] The invention relates to a marking object with at least one object carrier and at least one object blank held by the object carrier, the object being markable by a marking device. Furthermore, the invention also relates to a marking device for marking such a marking object with at least one marking unit, at least one marking object holding device and at least one defined or definable marking pattern, the marking unit and the marking object holding device being movable relative to one another in the main transport direction.
[0003] 2. Description of Related Art
[0004] Marking objects of the type under consideration have long been known and are used in industrial and commercial practice, often within the framework of housing and connection identifications, for example, in the form of labels, of self-adhesive or clip-in identification strips, in the form of identification cards, notch strips, stick-in tags, tag plates, clamp strips, marking sleeves, marking tags or other molded articles. These objects are generally held in a larger number of items by the object carrier. For molded articles, the object carriers are often frames, for example, of plastic, the object being joined to the object carrier which is made as a frame by way of a crosspiece which constitutes a scored site. By separating the crosspiece, the molded part can then be released from the object carrier.
[0005] For flat object blanks, therefore especially for labels or marking tags, several labels or marking tags are located next to one another on a flat object carrier, often a flat, coated paper web or preferably a plastic injection molding.
[0006] The marking objects for marking of the object are conventionally inserted into a marking device or into a marking object holding device of the marking device and are drawn in by the marking device, whereupon the object blanks are provided with a marking pattern, generally alphanumeric characters. The marking unit responsible for the actual marking is generally a printer or a printing head which performs marking by applying ink. These printers have been known for a long time, the printer generally being intended for printing on paper. A printer with which marking objects of plastic which have several marking tags as the object blanks can be printed is known, for example, from German Patent Application DE 10 2006 003 056 A1.
[0007] However, the marking unit can also be a pressing or engraving tool which by applying pressure or by metal cutting delivers the given marking pattern into the respective object blank.
[0008] The marking of a marking object with known marking devices is subject to some disadvantages. For example, in practice, often only a few of the objects encompassed by the marking object are needed at the same time so that marking objects are only partially marked in one pass, i.e., only some of the object blanks are marked, and the marking objects with the remaining unmarked object blanks are generally not further used, but are disposed of unused as scrap.
[0009] Furthermore, in the operation of a marking device, it must be accurately watched that the marking objects are held and guided in the uniquely correct orientation by the marking object holding device since the marking pattern otherwise is incorrectly applied to the marking object. In particular, for asymmetrical marking objects or object blanks located asymmetrically in the object carrier, misalignment of the marking object in the marking object holding device leads to faulty marking of the object blanks which then can no longer be further used.
[0010] Therefore, when using different marking objects, for example, when using marking objects of different manufacturers or also only when using different types of marking objects, suitable set-up—parameterization—of the marking device must be observed. This parameterization conventionally comprises consideration of the material comprising the marking object because, for example, it dictates how thickly the ink is applied when executing the marking, or for example, also with what temperature the inscribed object should be subsequently dried or with which irradiation intensity the object should be irradiated. Faulty parameterization of the marking device, therefore parameterization which does not consider the particulars of the marking object used, likewise leads to the marking objects not being correctly marked and only becoming scrap.
SUMMARY OF THE INVENTION
[0011] The object of this invention is, therefore, to avoid the indicated disadvantages of known marking objects and of known marking devices for marking of marking objects, at least in part.
[0012] This object is achieved, first of all, in accordance with the invention for the marking objects under consideration in that the object carrier comprises at least one identification means, the identification means containing at least one item of information relating to the marking object and/or at least one item of information relating to the marking object being able to be stored in the identification means. The configuration of the marking object in accordance with the invention results in that the information relating to the marking object is linked or can be linked directly to the marking object so that the information necessary for correct marking of the marking object or of the object blanks of the marking object can be obtained from the marking object itself or can be filed on the marking object itself.
[0013] In one configuration of the invention, the identification means performs inscribing and/or engraving and/or embossing and/or in perforation of the object carrier, this configurations being especially suitable for more valuable marking objects since they can be provided easily and at low cost. In particular, for high quality marking objects and object blanks, the use of electronic data media as the identification means is also advantageous, especially so-called RFID (radio frequency identification) chips or magnetic strips enabling contactless reading and storage of information in the identification means; this is of great benefit mainly for sensitive marking objects.
[0014] In one preferred embodiment, the object carrier has at least one crosspiece, the identification means at least partially being provided on the crosspiece of the object carrier. However, two crosspieces which run essentially parallel to one another are especially advantageous, these crosspieces then being provided mainly such that, for proper use of the marking object in a marking device, the crosspieces point in the main transport direction of the marking object. In this configuration, the crosspieces can also be used at the same time to make positive or nonpositive contact with the marking object by the transport device of the marking device—for example, driven rolls which press against one another—and to transport the marking object in the main transport direction.
[0015] It is especially advantageous if there are several identification means on the object carrier of the marking object such that the item of information of at least one of several identification means can be detected regardless of the orientation of the marking object and the information can be stored in at least one of several identification means regardless of the orientation of the marking object.
[0016] In one advantageous configuration of the invention, the item of information of the identification means relating to the marking object is the manufacturer identification and/or the type identification, with which the manufacturer of the marking object and the type of marking object can be easily determined. The type identification can be an “abstract” type which does not comprise concrete data such as, for example, the type of material used for the object blanks. In this case, “concrete” information for describing the marking object of the pertinent type can be determined only by comparison with a database which can be encompassed, for example, by the marking device.
[0017] In another advantageous configuration of the invention, the item of information of the identification means relating to the marking object—symmetry identification—indicates whether the marking object is symmetrical or asymmetrical. A marking object is called symmetrical when the object blank is held or located symmetrically on the object carrier so that the three-dimensional arrangement of object blank at a fixed point does not change when the marking object is turned by 180°. This information can be, for example, used specifically for monitoring the correct feeding of a marking device with the marking objects in accordance with the invention. If the marking object is symmetrical, it is irrelevant with which of the two face sides the marking object is introduced into the marking device, i.e., which of the two face sides is forward when viewed in the main transport direction.
[0018] In this connection, it has been found to be especially advantageous if the marking object is made such that the item of information of the identification means relating to the marking object describes the orientation of the marking object, especially indicates whether the identification means is on the front or back of the marking object and/or on which side of the front and/or back of the marking object the identification means is located. By this measure, the orientation of the marking object can be very easily detected from the outside, by which it can be assessed whether the marking object is suitably aligned for further processing.
[0019] In one especially preferred embodiment of a marking object in accordance with the invention, the identification means is set up such that the item of information regarding which object blank has been marked or which object blank has not yet been marked is stored or can be stored in it (object blank identification). This advantageous configuration of the invention allows a suitable marking device to properly mark even already partially marked marking objects or marking objects with object blanks already removed. In this way, the marking objects which have only some of the originally present object blanks can also be further used.
[0020] In another advantageous configuration, it is also provided that the identification means is provided on the outer edge of the object carrier, especially specifically on the outer edge with which the marking object in proper use can be introduced first into the marking device. This ensures that the information relating to the marking object is being detected while the marking object is still being positioned.
[0021] The initially described object is also achieved in accordance with the invention in the marking device under consideration by at least one detection and/or influencing device being provided for interaction with the identification means, and by way of the detection and/or influencing means, at least one item of information relating to the marking object can be detected and/or at least one item of information relating to the marking object can be stored in the identification means. Because the marking device in accordance with the invention is suitable for using the marking objects in accordance with the invention in the proper manner, specifically such that the information which is to be stored or which is contained in the identification means of the marking object can be detected or stored, the information described above in conjunction with the marking object in accordance with the invention can be used for processing of the marking object in the marking device in the aforementioned advantageous manner.
[0022] In one preferred configuration of the marking device, it is provided that, before marking of the object blanks of the marking object,] the item of information relating to the marking object is detected and held by the detection and/or influencing means, especially specifically the manufacturer identification and/or the type identification and/or the orientation and/or the item of information about the marked or unmarked object blanks (object blank identification) of the marking object is detected and held by the detection and/or influencing means.
[0023] Here, if the point is that the item of information relating to the marking object can be detected by the detection and/or influencing means, specifically by “interaction” with the identification means, this of course presupposes that the marking device somehow encompasses a type of data processing means. This goes without saying and does not require further explanation. In exactly the same way, it goes without saying that such a data processing means is used altogether for implementation of the functionality described here and for corresponding control of the marking device. For example, if the point is that, with the detection and/or influencing means, the item of information relating to the marking object is detected and held, thus technically the use of a data processing means with which the described functionality is implemented is meant. Both an item of information of an identification means can be read out by the detection and/or influencing means, and the item of information can be written into the identification means, i.e., stored in it, and an item of information which has been read out of the identification means can be evaluated and stored by the data processing means.
[0024] In one preferred embodiment, the detected and stored item of information relating to the marking object is used in the marking device for parameterization and control of the marking unit. This means especially that, for example, the item of information relating to the orientation of the object blanks leads to suitable alignment—especially rotation—and/or scaling of the marking pattern so that marking of the object blanks can be carried out independently of the location in the marking object in the marking object holding device. By detecting the orientation of the object blank or blanks, the marking device can adapt the given marking pattern such that the marking can be corrected applied to the intended object blank. Misalignment of the marking objects is accordingly no longer possible in the marking device in accordance with the invention since the marking device adapts the marking pattern which is present in an electronic data format to the detected alignment of the marking object by a corresponding transformation. These transformations of video data—for example, translation, rotation, mirroring—are conventionally known.
[0025] According to another advantageous embodiment of the marking device, it is provided that the detected and stored item of information relating to the marked or unmarked object blanks of the marking object (object blank identification) be used for triggering of the marking unit and/or for adaptation of the marking pattern, specifically such that only unmarked object blanks are marked by the marking unit. The marking device made in this way also makes it possible to re-use even partially used marking objects, i.e., marking objects in which only some of the object blanks are marked. The marking device is specifically able to obtain information about which object blanks of the marking object are still present and still unmarked and/or which object blanks are no longer present or have already been marked. The marking device in accordance with the invention can recognize by comparison of this item of information with the defined or definable marking pattern which parts of the defined marking pattern at the corresponding position can no longer be marked, and it is therefore possible for the marking device to react to such a collision. This can take place either by the marking unit not undertaking any marking on the position of the already marked object blanks or by the defined marking pattern being adapted, for example, by no longer markable positions of object blanks being shifted to still markable positions of still unmarked object blanks.
[0026] In particular there is still a host of possibilities for embodying and developing the marking object in accordance with the invention and the marking device in accordance with the invention as will be apparent form the following description of embodiments in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0027] FIG. 1 shows one exemplary embodiment of a marking object in accordance with the invention in a plan view,
[0028] FIG. 2 shows another exemplary embodiment of a marking object in accordance with the invention in a plan view,
[0029] FIG. 3 shows still another exemplary embodiment of a marking object in accordance with the invention in a plan view,
[0030] FIG. 4 shows a schematic of one exemplary embodiment of a marking device in accordance with the invention in a side view and
[0031] FIG. 5 shows a perspective of a printer as a marking device.
DETAILED DESCRIPTION OF THE INVENTION
[0032] FIGS. 1 to 3 each show a marking object 1 with an object carrier 2 and several object blanks 3 which are held by the object carrier 2 . In FIGS. 1 and 3 , the object blanks 3 are arranged symmetrically in columns; conversely, the object blanks 3 in FIG. 2 are arranged asymmetrically. The marking object 1 shown in FIGS. 1 and 3 is thus made symmetrically, i.e., it is irrelevant with which of the two face sides the marking object 1 is introduced into the marking device 7 . In contrast, the marking object 1 shown in FIG. 2 is asymmetrical so that in the marking of the object blanks 3 , it must be considered with which face side the marking object 1 is introduced into the marking device 7 . The object blanks 3 can be marked by the marking device which is shown only in FIG. 4 .
[0033] The marking objects 1 shown in the figures are each made such that the object carrier 2 comprises several identification means ( 4 a , 4 b , 4 c , 4 d ), the identification means ( 4 a , 4 b , 4 c , 4 d ) containing at least one item of information which relates to the marking object 1 . In the marking object 1 shown in FIG. 3 , an item of information relating to the marking object 1 can also be stored in the identification means 4 d.
[0034] It can be recognized in FIGS. 1 to 3 that the object carrier 2 comprises two crosspieces 5 which run essentially parallel to one another, the identification means ( 4 a , 4 b , 4 c , 4 d ) being provided on the crosspieces 5 of the object carrier 2 . The crosspieces 5 here run parallel to the main transport direction T in which the marking object 1 is inserted into the marking device 7 .
[0035] The marking objects 1 shown in FIGS. 1 to 4 , likewise, have in common that there are several identification means ( 4 a , 4 b , 4 c , 4 d ) on the object carrier 2 such that the information of at least one of several identification means ( 4 a , 4 b , 4 c , 4 d ) can be detected independently of the orientation of the marking object 1 . For example, it can be recognized that the identification means 4 a and the identification means 4 c are located in each of opposite corners of the marking object 1 so that, when using the marking object 1 , it is irrelevant with which of its two face sides the marking object is introduced, for example, into a marking device. The same also applies to the identification means 4 b which are provided on opposite locations on the crosspieces 5 .
[0036] In the illustrated embodiments, the item of information of the identification means ( 4 a , 4 b , 4 c , 4 d ) relating to the marking object 1 is a manufacturer identification 4 a and a type identification 4 b . Furthermore, there is also a symmetry identification 4 c which indicates whether the marking object 1 or the arrangement of object blanks 3 on the marking object 1 is symmetrical or asymmetrical. In the embodiments shown in FIGS. 1 to 3 , the symmetry identification 4 c is in opposite perforations, the perforations for a symmetrical marking object 1 being square and of the same size ( FIGS. 1 and 3 ), and for the asymmetrical marking object 1 as shown in FIG. 2 their being of different size so that altogether it can be recognized that there is asymmetry and which of the different face sides of the marking object 1 is in fact being detected.
[0037] Marking objects which are not shown here are characterized in that the item of information of the identification means relating to the marking object describes the orientation of the marking object, specifically especially indicates whether the identification means is on the front or back of the marking object and/or on which side of the front and/or back of the marking object the identification means is located.
[0038] The embodiment as shown in FIG. 3 is characterized in that the identification means is an object use identification 4 d which is set up such that the information as to which of the object blanks 3 has been marked or which object blanks 3 has not yet been marked is stored or can be stored in it. In this way, it is fundamentally possible to mark incompletely marked marking objects 1 by a suitably equipped marking device such that only the still unmarked object blanks 3 are used.
[0039] In the illustrated embodiments the identification means ( 4 a , 4 b , 4 c , 4 d ) are on the outer edge 6 of the object carrier 2 so that it is easily established at what locations of the marking object 1 the information of the identification means ( 4 a , 4 b , 4 c , 4 d ) can be read off and stored. The illustrated marking objects 1 are preferably made as plastic injection moldings and the object blanks 3 as marking tags for electrical or electronic devices, and the marking tags can preferably be locked or inserted in the corresponding recesses on the housings of the devices.
[0040] FIG. 4 partially shows a marking device 7 for marking of at least one marking object 1 . The marking device 7 comprises a marking unit 8 and a marking object holding device 9 which are both shown in FIG. 5 . The marking device 7 also comprises a marking pattern with which the object blanks 3 are to be identified. The marking unit 8 and the marking object holding device 9 can be moved relative to one another in a main transport direction T, the main transport direction T, in the illustrated exemplary embodiment, into the plane of the paper in FIG. 4 . The marking object 1 used is one of the above described marking objects 1 with an object carrier 2 and several object blanks 3 which are held by the object carrier 2 , the object carrier 2 comprising identification means 4 .
[0041] For interaction with the identification means 4 , there is a detection and/or influencing device 10 , and by way of the detection and/or influencing device 10 , an item of information relating to the marking object 1 can be detected and an item of information relating to the marking object 1 can be stored in the identification means 4 .
[0042] The marking device 7 is also characterized by the item of information relating to the marking object 1 being detected and stored before marking of the object blanks 3 of the marking object 1 with the detection and/or influencing device 10 . This item of information or the detected information in the illustrated embodiment is the manufacturer identification 4 a , the type identification 4 b , the symmetry identification 4 c and the object blank identification 4 d.
[0043] In the illustrated marking device 7 , the detected and stored information relating to the marking object 1 is used for parameterization and control of the marking unit 8 ; this makes the illustrated marking device 7 especially advantageous since the information belonging to the actually used marking object 1 is necessarily always used.
[0044] In the illustrated embodiment, the information relating to the orientation of the object blanks 3 is used for suitable alignment—especially specifically rotation—and scaling of the marking patterns so that marking of the object blanks 3 can be carried out independently of the position of the marking object 1 in the marking object holding device 9 . In particular, the detected and held information relating to the marked or unmarked object blanks 3 of the marking object 1 —object use identification—is used for triggering of the marking unit 8 or also for adaptation of the marking pattern so that only unmarked object blanks 3 are marked by the marking unit 8 .
[0045] Finally, the marking device 7 shown in FIG. 4 is characterized in that the marking device 7 , in the identification means 4 , stores or updates the information regarding which object blanks 3 have been marked by the marking unit 8 .
[0046] FIG. 5 shows a printer which is used as the marking device 7 and which can be an inkjet printer. The printer 7 has a printing head which is only suggested here as the marking unit 8 and a marking object holding device 9 . The marking object holding device 9 is used both for holding and also for transport of the marking object 1 to be marked in the main transport direction. For transport of the marking object 1 through the marking device 7 there can be several rollers 11 (which are only suggested in FIG. 4 ) in the marking device 7 , and which are aligned with one another such that they make positive and nonpositive contact with the crosspieces 5 of a marking object 1 which has been inserted into the marking object holding device 9 , and thus, transport the marking object 1 in the main transport direction. FIG. 5 also shows a data processing means 12 which interacts with the detection and/or influencing device 10 . | A marking object having at least one object blank ( 3 ) and held by an object carrier ( 2 ), the object blank ( 3 ) being markable by a marking apparatus ( 7 ). To configure the marking objects such that the known drawbacks are eliminated, the object carrier ( 2 ) has at least one identification means ( 4 a, 4 b, 4 c, 4 d ) that contains at least one piece of information relating to the marking object ( 1 ) and/or the identification means ( 4 a, 4 b, 4 c, 4 d ) can be used to store at least one piece of information relating to the marking object ( 1 ). | 1 |
RELATED APPLICATIONS
[0001] This application is a continuation-in-part of application Ser. No. 09/867,087 filed May 29, 2001.
BACKGROUND OF THE INVENTION
[0002] The present invention relates to a microtitration plate.
[0003] Microtitration plates are used for most varied microbiological, cell-breeding, and immunological techniques. In particular, microtitration plates are employed for the PCR (polymerase-chain-reaction) or the breeding of microorganisms or cells.
[0004] Microtitration plates have already been known which have a frame with a plate to which a multiplicity of vessels are fixed which have a receiving portion protruding from the underside of the plate and are accessible from the upper surface of the plate through apertures. The vessels are also referred to as “wells”. The current 96-type microtitration plates have 8×12=96 vessels in rows and columns. However, microtitration plates having a larger number of vessels are used more and more.
[0005] Single-component microtitration plates in polystyrene are unsuitable for the PCR, particularly because the softening temperature of this plastic (about 85° C.) is exceeded during the PCR.
[0006] Single-component microtitration plates in polypropylene generally are adapted to be used for the PCR. However, they are flexurally soft, tend to be distorted, are uneven and are manufactured only at large tolerances and undergo large tolerance variations when in use. Specifically, they are not particularly suited for being handled by automatic devices because their softness makes it difficult for automatic devices to grip them. Further, their low dimensional stability may have the consequence that the proportioning needles will contact the walls while being introduced into the vessels. Furthermore, heat transfer into the walls is poor because the thick walls of the vessels impede it, which is adverse to temperature regulation and the length of cycle times during the PCR.
[0007] It is particularly in breeding microorganisms or cells that the sample requires sufficient oxygen supply. In the 96-type microtitration plates, this can be ensured because of the relatively large apertures of the vessels. However, in microtitration plates having a larger number of vessels, e.g. 384, oxygen supply may be impaired very much by the reduced cross-sections of the apertures. In addition, it would be desirable to ensure oxygen supply even if the apertures are closed in order to avoid transversal contaminations between the samples of various vessels.
[0008] Attempts to avoid transversal contaminations are also made in other applications of microtitration plates. To this end, there are sealing foils which are welded onto the upper surface of the microtitration plate and have to be released again if an access is required to the contents of the vessels. In addition, there are rubber mats which have cones at their underside in order to sealingly engage the apertures of the vessels when placed on the microtitration plate. Further, there are plastic strips which are designed with stoppers at their underside in order to be forced into the apertures of a row of vessels in the microtitration plate.
[0009] The known sealing methods are complicated in use and do not satisfy the increased requirements to tightness.
[0010] Therefore, it is the object of the invention to provide a microtitration plate having more favourable characteristics in use.
[0011] In addition, a technique for the manufacture of the microtitration plate will be provided.
SUMMARY OF THE INVENTION
[0012] The object of the invention is achieved by providing a microtitration plate comprising:
[0013] a frame made of a stiff first plastic which has a plate with a multiplicity of holes, and
[0014] a multiplicity of vessels made of a second plastic suited for the PCR and/or exhibiting permeability to oxygen, which are fixedly connected to the plate by directly molding them to the holes, have a receiving portion protruding from the underside of the plate, and are accessible from the upper surface of the plate through apertures, means for formlockingly connecting the vessels with the plate.
[0015] Because of its stiffness, the frame of the microtitration plate is particularly suited for being handled by automatic devices. Preferably, its edge is provided with a bordering protruding from the underside which increases its stability, may form a surface to stand on and a surface for engagement by the automatic device. For this purpose, the frame may be manufactured so as to have particularly low distortion and particularly low tolerance. The first plastic may be an amorphous plastic or even a partially crystalline, heavily filled plastic. The plastic concerned may be polycarbonate which actually is unsuited for the PCR or oxygen supply. Since this plastic is confined to the frame, however, it allows to utilize its advantageous characteristics even for microtitration plates for the PCR or oxygen supply to samples.
[0016] The vessels are made of a plastic different from that of the frame. It is a second plastic which is suitable for the PCR and/or is permeable to oxygen. Suitability for the PCR may be given, in particular, by an increased resistance to temperatures (up to about 90 to 95° C.). It may further be given by a reduced plastic affinity or neutrality of the plastic to DNA or other substances of the PCR. It preferably is a soft and/or partially crystalline plastic. Preferably, the second plastic can be polypropylene.
[0017] Each vessel is molded directly to the hole associated therewith. Generally, the vessels can be positively, formlockingly connected to the plate and/or can be non-positively, frictionally connected with the plate, and/or be connected by molding the vessels in holes having varying cross-sections in an axial direction and/or to the marginal area of the holes on at least one side of the plate, while connecting them thereto in a non-positive manner. With a vessel being molded in a hole, it becomes bonded to the plate by the material the vessel is made of. Under a formlocking connection is understood a connection in which two connected parts are provided with interengaging elements having complementary forms or shapes. Upon connection of the two parts, the interengaging complementary elements prevent the two parts from being disconnected.
[0018] Molding the vessels to the plate directly provides very short flow paths of the material in molding, which allows to achieve particularly small wall thicknesses which preferably are in the range of about 0.05 to 0.25 mm and, in particular, may be about 0.1 mm. This favors heat transfer. The vessel bottom of each vessel has a gate mark and from which the material fills the first wall portion of a reduced wall thickness and an upper wall portion connected to the plate. A gate mark is a point corresponding to a point in a mold for an injection-molded part at which a plastified plastic enters the mold. On a finished part, the gate mark is a visible as e.g., an uneveness on a surface. It is preferred that the upper wall portion be designed as a collar of an increased wall thickness, which allows to manufacture the microtitration plate with particularly small tolerances.
[0019] Since the frame is manufactured from a first plastic and the vessels are manufactured from a second plastic the best solutions possible will be achieved with materials which correspond to the desired functions of the frame and vessels. Higher rigidity, better planarity, a lower tendency to distortion, and smaller tolerances are achieved by using an amorphous, rigid, and highly temperature-resistant material for the frame. The extremely thinness of the walls for better heat transfer is achieved by molding the vessels thereto in a direct way. The frame is not filled via the vessels so that the entire pressure gradient always is available to one vessel only. The vessels may be molded of soft materials suited for the PCR. It is uncritical to mold the frame. It preferably may have several edge-side gate marks (about four to six) provided on the frame edge.
[0020] In order to ensure an increased permeability to oxygen the second plastic preferably is silicon. In particular, it may be LSR (Liquid Silicon Rubber).
[0021] According to the inventive manufacturing technique, the frame and vessels are produced by a multi-component molding technique. In the simplest case, it is a two-component molding technique or “twin-shot” technique.
[0022] For manufacture at particularly low tolerances, it is preferred to mold the frame initially and the vessels subsequently. This has the advantage that the frame first may undergo a certain shrinkage before the vessels are molded thereto. The time interval from molding the frame to molding the vessels thereto may be chosen so that the shrinkage of the frame (by cooling it down) essentially is effected completely. Once the vessels are molded on, shrinking techniques virtually do not impair the dimensional stability of the microtitration plate any longer. It specifically is the tolerance of the vessel-to-vessel distance which, thus, can be confined to very low values (about t 0.15 mm). This makes it easier to introduce proportioning needles with no wall contact.
[0023] It is particularly advantageous here if the upper wall region of the vessels is designed as a collar of an increased wall thickness because the collar may compensate hole position tolerances that have remained during molding.
[0024] The object further is achieved by providing a microtitration plate which comprises:
[0025] a rigid frame which includes a plate,
[0026] a multiplicity of vessels, which are fixedly connected to the plate, have a receiving portion protruding from the underside of the plate, and are accessible from the upper surface of the plate through apertures, a rigid lid adapted to be releasably attached on the upper surface of the plate, and
[0027] at least one seal between the lid and the plate which is of an elastic material which deviates from the plastic of the plate and/or the lid and is fixedly connected to the lid and/or the plate in order to close the apertures when the lid is disposed on the plate.
[0028] In other words, according to the invention, the plate and/or the lid is designed with at least one seal of an elastic material deviating from the material of the plate and/or the lid. In particular, the material concerned may be a thermoplastic, elastomer, thermoplastic elastomer or rubber. The connection of the seal to the plate and/or the lid may be a non-positive and/or positive and/or by the material of the vessel when the vessel is bonded to the plate. Thermoplastic elastomers, in particular, enable a non-positive connection with matching materials of the plate and lid. In particular, in a microtitration plate, the seal may be provided on a collar of the vessels. If the vessels are manufactured from an elastic material, there is a possibility of forming the seals integrally with the vessels here.
[0029] In this microtitration plate, the at least one integrated sealing, in conjunction with a rigid lid, makes possible rapid and simple sealing of the apertures which satisfies the high requirements to tightness. It is particularly advantageous for handling and sealing that the lid is designed so as to be adapted to be locked with the frame, specifically by locking it with the marginal area of the frame. Specifically if designed with a plane seal at its underside, the lid can also be used with known microtitration plates having thermoplastic sealing collars at the apertures of the vessels.
[0030] If the at least one seal is to be connected to the plate annular contours enclosing the apertures are preferred. If connected to the lid, the seals particularly may be annular, plug-shaped, mat-shaped or lip-shaped seals.
[0031] For the manufacture of this microtitration plate, it again is a multi-component molding technique which preferably is employed, particularly a two-component molding technique (a “twin-shot” technique) or a three-component molding technique (a “three-shot” technique. A three-component molding technique may be employed particularly if two different plastics are used for the frame and vessels, and a third plastic is employed for the at least one seal.
[0032] It is preferred that the frame be molded initially and the at least one seal is molded to the frame subsequently and/or the lid is molded initially and the at least one seal is molded to the lid subsequently. If required, the frame is molded integrally with the vessels. However, the vessels may be molded in a second step and the at least one sealing in a third step.
BRIEF DESCRIPTION OF THE DRAWINGS
[0033] The invention will now be explained in more detail with reference to the accompanying drawings of embodiments. In the drawings:
[0034] FIG. 1 shows a 96 type microtitration plate with a frame and vessels made of various plastics in a plan view;
[0035] FIG. 2 shows the same microtitration plate in an oblique perspective view from bottom;
[0036] FIG. 3 shows the same microtitration plate in a largely magnified vertical section-in-part through the plate of the frame and a vessel;
[0037] FIG. 4 shows a 96 type microtitration plate which is integrally made from a single plastic and has integrated annular sealings in an oblique perspective view from top;
[0038] FIG. 5 shows a microtitration plate modified by connection webs between the sealings as compared to the embodiment of FIG. 4 in an oblique partial perspective view from top;
[0039] FIG. 6 shows a microtitration plate having a lid with integrated plug-shaped sealings in a partial perspective view.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0040] In the drawings, the same elements are designated by identical reference numerals. The description pertaining thereto applies to all of the embodiments.
[0041] Referring to FIGS. 1 through 3 , a microtitration plate 1 comprises a frame 2 and a multiplicity of vessels 3 . There is a total of 96 vessels arranged in eight columns and twelve rows.
[0042] The frame 2 has a substantially rectangular plate 4 the outer edge of which is surrounded by a bordering 5 which protrudes approximately perpendicular from the underside of the plate 4 , i.e. beyond the vessels 3 . At bottom, the bordering 5 , as is known, has an expansion 6 which enables stacking on the upper surface of an appropriate microtitration plate 1 .
[0043] The frame 2 has a total of ninety-six holes 2 ′ in the plate 4 . These have a profile 2 ″ of the cross-section which widens towards the upper surface 7 of the plate 4 in two portions of different conicity and towards the underside 8 of the plate 4 in a conical portion.
[0044] In a first molding step, the frame 2 is integrally molded from a plastic which is relatively rigid when cured. Gate marks are formed at the edge of frame 2 , e.g. at the lower edge of the bordering 5 .
[0045] At their base, vessels 3 have a cup-shaped bottom 9 which is bordered by a conical wall portion 10 of a very small wall thickness (about 0.1 mm). Above it, there is a wall portion 11 the wall thickness of which gradually increases towards the top. At its outside, it has the same conicity as the wall portion 10 . At its inside, however, it is designed nearly cylindrically, which results in an approximately wedge-shaped profile of the cross-section.
[0046] Wall portion 11 terminates in a collar 12 which also is of a largely increased wall thickness with respect to wall portion 10 . Vessels 3 are molded to plate 4 in the area of collar 12 . To this end, a collar 12 externally bears against the inner periphery of holes 2 ′. It further has a projection 13 , 14 at the upper surface 7 and the underside 8 of plate 4 , respectively. With the engagement of the projections 13 , 14 with the upper surface 7 and the underside 8 , a formlocking connection of the collar 12 and, thereby, of the vessel 3 with plate 4 is formed.
[0047] As shown in FIG. 3 , the collar 12 has an outer profile 12 ′ of the cross-section that widens likewise as the profile 2 ″ of the hold 1 ′, toward the upper surface 7 of the plate 4 in two portions of different conicity and toward the underside 8 of the plate 4 in a conical portion, i.e., the cross-sectional profile 2 ″ of the hole 2 ′ and the cross-sectional profile 12 ′ of the collar 12 are complementarily formed. Therefore, a form locking connection is already formed when a vessel 3 is inserted in the hole 2 ′. The projections 13 , 14 only inhance the already formed form locking connection. The collar 12 can have not two but only one projection 13 or 14 . Both projections are necessary when the complementary profiles of the vessel 3 and the hole 2 ′ have a circular cross-section.
[0048] Though a specific cross-sectional profile of the hole 2 ′ and the vessel 3 was described, it should be understood that they can have a different shape, e.g. the hole wall can have a convex profile, with the outer surface of the collar having a concave profile. Further, the complementary profiles of the hole 2 ′ and the vessel 3 can be formed of two sections, a cylindrical section and a conical section widening to the upper surface 7 of the plate 4 or to the underside 8 . In case the conical section widens toward the upper surface 7 of the plate 4 , the collar 12 is provided with a bottom projection 14 . If the comical section widens to the underside 8 of the plate 4 , the collar is provided with the upper projection 13 .
[0049] In the area of collar 12 , vessels 3 have a cross-section expanding towards the top in two portions of different conicity. Vessels are accessible from the upper surface of plate 4 through apertures 15 .
[0050] All of the vessels are simultaneously molded directly to the frame 2 and the holes 2 ′ thereof. Each vessel 3 has its own central gate mark at the underside of bottom 9 . This helps achieve shorter flow paths of the plastic which are made possible by the particularly small wall thickness in wall portion 10 . The material used is polypropylen or LSR, for example, for the purpose of the PCR or oxygen supply to a sample inside the vessel.
[0051] FIG. 4 shows a microtitration plate 1 ′ in which the frame 2 ″ and the vessels 3 ′ are integrally made of a single plastic in a known manner. The outer shape of microtitration plate 1 ′ substantially corresponds to that of the preceding example with the vessels 3 ′, however, having a substantially uniform course of wall thickness and are fused to plate 4 ′ with no projections. At the edge, plate 4 ′ is connected, in a known manner, to bordering 5 ′ which has the expansion 6 ′ at the bottom.
[0052] Vessels 3 ′ are accessible from the top through apertures 15 ′ with an annular sealing 16 made of an elastic material being disposed around each aperture. In the example, it is a plastic which is capable of getting connected to the plastic of microtitration plate 1 ′ by being bonded thereto.
[0053] Instead, a non-positive connection may be produced by placing seal 16 in an undercut groove in the upper surface of plate 4 ′.
[0054] Preferably, seals 16 are fixedly connected to microtitration plate 1 ′ by a multicomponent molding technique.
[0055] Now, it is possible to sealingly close apertures 15 ′ by placing thereon a lid (not shown) made of a rigid material. The lid may approximately have the dimensions of plate 4 ′. Preferably, it is locked in the marginal area of microtitration plate 1 ′. Such locking may be effected, for example, in the recesses 17 which the bordering 5 ′ has directly beneath plate 4 ′.
[0056] The embodiment of FIG. 5 differs from the aforementioned in that the adjoining annular seals 16 are connected to each other by straight-lined webs 18 , 19 which extend in the row and column directions. This may be advantageous particularly for technical reasons of manufacture, but also for reasons of fixedly connecting the seals to the microtitration plate 1 ′ or for providing additional sealing.
[0057] Referring to FIG. 6 , a microtitration plate 1 ′ is shown which is made of a single material only in correspondence to the one of FIG. 4 . However, there are no annular seals 16 here. Plate 4 ′ of microtitration plate 1 ′ has, seated thereon a lid 20 . It has a plate 21 the contours of which substantially are the same as those of the plate 4 ′. Plate 21 is supported on the upper surface of plate 4 ′ in marginal areas 21 ′. It is spaced by a small gap from plate 4 ′ in a region 21 ″ between marginal areas 21 ′. This allows it to be placed onto conventional microtitration plates which have sealing collars at the upper surface of retaining plate 4 ′.
[0058] In region 21 ″, plate 21 has plug-like seals 22 which protrude from its underside. These plug-like seals 22 have a circumferential sealing bulge 23 at their outer periphery.
[0059] Each aperture 15 ′ of vessels 3 ′ has associated thereto a seal 22 . Here, seals 22 engage apertures 15 ′ so as to sealingly cause their sealing bulges 23 to bear against the inner wall of vessels 3 ′.
[0060] Seals 22 are disposed in appropriate recesses of plate 21 . They are connected to each other by short webs 24 , 25 which extend in the row and column directions.
[0061] Borderings 26 protrude from the underside of the plate at the edge thereof, from which borderings catch projections 27 protrude inwardly which are adapted to be locked in the recesses 17 (see FIG. 4 ) of microtitration plate 1 ′. Handles 28 project upwardly from borderings 26 . Those make it easier for lid 20 to be locked. Furthermore, pivoting the handles 28 makes it possible to disconnect the locking engagement between catch projections 27 and recesses 17 because the borderings 26 will be pivoted along.
[0062] Preferably, lid 21 with seals 22 is also manufactured by a multi-component molding technique. | A microtitration plate has a frame ( 2 ) made of a first stiff plastic and having a plate ( 4 ) with multiplicity of holes ( 2 ′), and a multiplicity of vessels ( 3 ) made of a second plastic suited for the PCR and/or exhibiting permeability to oxygen, which are fixedly connected to the plate ( 4 ) by directly molding them to the holes ( 6 ), which have a receiving portion ( 9, 10, 11 ) protruding from an underside ( 8 ) of the plate ( 4 ), and which are accessible from an upper surface ( 7 ) of the plate through apertures ( 15 ). | 1 |
THE TECHNICAL FIELD
[0001] The invention relates to a device for insertion of a cannula of e.g. and infusion set for intermittent or continuous administration of a therapeutical substance, such as e.g. insulin. The insertion device assures that before, during and after insertion the insertion needle is not visible to the patient.
BACKGROUND OF THE INVENTION
[0002] The document U.S. Pat. No. 6,387,078 pertains to an automatic injection apparatus which injects a single, pre-measured dose of stored medicine intramuscularly or transdermally, and the injection apparatus automatically retracts the hypodermic needle into the device after the injection is completed. The user presses the distal end i.e. the needle end, of the device onto the desired injection site and presses the actuation button. This releases the plunger-syringe-combination from its temporary engagement with the housing. The plunger-syringe-combination together with the spring-to-plunger-coupling are then forced away from the proximal end, i.e. the actuation end, of the housing by an energized driver spring. The driver spring propels the plunger-syringe-combination forward through the bore of the housing until the hypodermic needle exits the housing, and enters the recipient's tissue, and the syringe barrel touches the interior distal end of the housing. During this movement, a return spring positioned between the syringe assembly and the fixed, distal end of the housing becomes compressed and energized. When the liquid of the automatic injection apparatus is discharged by the plunger being pushed forward through the interior of the syringe barrel, the spring-to-plunger-coupling comes into contact with a splitter which disengages the driver spring from the plunger. Without the influence of the driver spring upon the plunger-syringe-combination, the energized return spring forces the plunger-syringe-combination to retreat rearward towards the proximal end of the device until the hypodermic needle is fully retracted into the housing.
[0003] As this automatic injection apparatus is directed toward injections of a pre-measured dose of stored liquid medicine where the plunger during injection pushes the liquid dose of stored medicine out of the apparatus, the solution will not be applicable for use when inserting an injection device as the handling and injection of a liquid under sterile conditions necessitates a complicated injection apparatus which need to interact with the liquid.
[0004] WO 2005/046780 (FIG. 97-102) describes a device used for automatic insertion of a cannula of an infusion device into the skin of a patient, and afterwards automatic retraction of the insertion needle. The insertion device has the form of an oblong cylinder (length 4× diameter) which is open in one end (1984) and provided with means for activation at the other end (1952). When the infusion set has been loaded onto the needle (1968) the lock member (1962) is moved in direction of the end provided with means for activation by the patient using projections (1974) which projections are accessible through a slot (1976) of the housing until barbs (1956) of the lock member (1962) engage an outer surface of the housing (page 26, I. 24-27). Then the open end (1984) is placed against the skin of the patient and the means for activation (1952) is activated. When activated shoulders (1954) on the means for activation engage, the barbs (1956) are pushed toward each other in order to disengage the barbs from the housing. When the barbs are clear of the housing the lock member, the needle hub, the retainer body and the associated infusion device are moved by a first spring in direction of the open end (1984). The inserter device moves the infusion device towards the skin of the patient thereby inserting the needle and the cannula of the infusion device. As the cannula is fully inserted, barbs (1964) of the needle hub (1965) engage ramped surfaces (1972) of the sleeve (1982), causing the barbs (1964) to be forced toward, one another. When the barbs (1964) have been forced sufficiently inwardly to clear ends (1988) of the main body (1980), the second spring (1966) then moves the needle hub (1965) in the direction of the activation means (1952). Thus the needle is removed from the infusion device leaving the infusion device in place on the skin while the retainer body remains in a position adjacent the open end of the sleeve so that once the insertion device is removed from the skin of the patient, the retainer body protects the patient from further contact with the needle.
[0005] This insertion device is rather complex and used for automatic insertion of a cannula of an infusion device into the skin of a patient. A feature illustrating the complexity of the unit is the fact that the two springs respectively biases the housing from the lock member and the retainer body from the needle hub while a main body is placed between the two spring systems to transfer the force from the first spring to the second spring.
[0006] An insertion device for medical devices is also described in DE 201 10 059, in this document the first insertion part is constituted by the housing 6 and the second insertion part, i.e. the part connected to the injection needle, is constituted by the plunger part 27 . The first insertion part according to this device is closed in the distal end where the distal end is the end opposite the end where from the injection needle protrudes during activation. The activation means of this device comprises two buttons 24 , 25 on the side of the cylindrical device.
[0007] According to the present invention the first insertion part 1 is shaped as a cylindrical tube which tube is open in both ends where the second insertion part 2 , which is connected to the injection needle and functions as a plunger, exceeds the distal end of the first insertion part both when the second insertion part is in a retracted and in a forward position relative to the first insertion part. The movable parts of the present invention are relatively large, e.g. the activation means of this device can be constituted by the second insertion part, and as a result the device is very robust and easy to use as the user just by watching the device will be able to predict how it functions.
SUMMARY OF INVENTION
[0008] The object of the invention is to provide a simple, non-expensive inserter for an infusion device which inserter would be easy and safe for the user to handle during use and safe to dispose of after use.
[0009] The invention concerns a device for insertion of a cannula into a subcutaneous or transcutaneously layer of skin of a patient. The device comprises a first insertion part and a second insertion part, a cannula holding part provided with a cannula, and an injection needle where
the second insertion part is connected to the injection needle and the injection needle is releasably combined with the cannula of the cannula holding part, the first insertion part covers the injection needle in a non-activated position and in an activated position the injection needle projects beyond the first insertion part, at least a part of the second insertion part and the first insertion part can be moved in relation to each other between at least one activated position and at least one non-activated position, further the second insertion part exceeds the distal end of the first insertion part.
[0013] This position of the second insertion part in relation to the first insertion part makes it possible to use the second insertion part as activation means. In one embodiment the second insertion part is provided with handling means for retraction of the insertion needle from the patients skin.
[0014] The cannula can be either a soft cannula which is inserted into the patients skin by a separate insertion needle. The insertion needle is then secured releasably or un-releasably to the second insertion part. The cannula can also be a self-penetrating cannula which stays positioned in the patients skin after insertion. The cannula then is the insertion needle and is the insertion needle/cannula is then only secured to the second insertion part before insertion.
[0015] In one embodiment an elastic element supports bringing the second insertion part which is connected to the injection needle from a forward i.e. an activated position to a retracted i.e. a non-activated position. The elastic element can comprise a spring being in contact respectively with a surface of the second insertion part and a surface of the first insertion part.
[0016] According to one embodiment at least a part of the second insertion part moves between at least one forward position and at least one retracted position surrounding the first insertion part.
[0017] According to one embodiment the second insertion part and the first insertion part are provided with interacting guiding means for guiding the a slidable movement over a certain distance of the first and second insertion parts in relation to each other.
[0018] According to one embodiment of the device the injection needle is unreleasably connected to the second insertion part. This is the case if the insertion device is intended for single-use.
[0019] According to a second embodiment the injection needle is releasably connected to the second insertion part. This is the case if the insertion device or at least a part of the insertion device is intended for multiple-use. If the insertion device is intended for multiple-use the first and the second insertion parts can be releasably connected to each other and then one part is reusable while the other part is disposable.
[0020] According to one embodiment the first insertion part comprises means for releasably connecting to a corresponding receiving portion placed on a patient's skin e.g. the receiving portion is part of a base plate fastened to the patients skin.
[0021] According to one embodiment of the invention the proximal end of the first insertion part is shaped as a cylindrical tube which can be releasably connected to a corresponding cylindrical portion placed on a surface on the skin of a patient, e.g. the receiving portion is attached to a base part which is positioned on a patient's skin before injection of the cannula-holding part.
[0022] According to one embodiment an elastic element supports bringing the second infusion part from a forward to a retracted position, the elastic element can e.g. be in the form of a helix metal spring, a rubber element or the like.
[0023] According to one embodiment the elastic element is unbiased or only slightly biased when the first and the second insertion parts are in a non-activated position.
[0024] According to one embodiment the first insertion part is supported against a surface while the guiding means guide the injection needle of the second insertion part through the surface and back again.
[0025] According to one embodiment the first insertion part is formed as a pipe section or a tube piece while the second insertion part is at least partly formed as a plunger corresponding to the interior of the first insertion part i.e. a part of the second insertion part can slide between a forward and a retracted position guided by the interior walls of the first insertion part.
[0026] According to one embodiment the insertion device is provided with means for manually injecting the injection needle ( 6 ) by manually pushing the second insertion part towards the surface of injection. Further retraction of the injection needle can also be done by manually pulling the second insertion part away from the surface of injection.
[0027] According to one embodiment the needle holding part of the second insertion part including the injection needle is retained in the first insertion part when the first and the second insertion parts are released from each other.
[0028] The first insertion part is shaped as a tube piece being open in both ends and having a round or angular transverse profile.
[0029] The insertion device can comprise locking means which locking means can lock the position of the first insertion part in relation to the second insertion part in the non-activated position. The locking means can comprise a protruding part positioned on the outer surface of the first insertion part combined with an opening or slit in the surface of the second insertion part.
DEFINITIONS
[0030] Distal—in the present text the word distal refers to parts which are far way from the patient's skin in the position the device takes during insertion, normally as far away as possible.
[0031] Proximal—in the present text the word proximal refers to parts which are close to the patient's skin in the position the device takes during insertion, normally as close as possible.
SHORT DESCRIPTION OF THE DRAWINGS
[0032] Embodiments of the invention will now be described with reference to the figures in which:
[0033] FIG. 1 is a cross-sectional view of a first embodiment of an insertion device of the invention where the insertion device is mounted in a receiver and the insertion needle is in a retracted position before activation;
[0034] FIG. 2 is a cross-sectional view of the embodiment of FIG. 1 in a position after activation of the insertion device and insertion of the cannula;
[0035] FIG. 3 is a side view of an insertion device of the embodiment shown in FIG. 1 before mounting in a receiver;
[0036] FIG. 4A is a side view of an insertion device of the embodiment shown in FIG. 1 after mounting in a receiver before activation, FIG. 4B-F are side views of base parts provided with a peripheral or central rectangular receivers for a cannula holding part with rectangular or round profile;
[0037] FIG. 5 is a cross-sectional view of another embodiment of an insertion device of the invention where the insertion device is mounted in a receiver and the insertion needle is in a retracted position before activation;
[0038] FIG. 6 is a cross-sectional view of the embodiment of FIG. 5 in a position after activation of the insertion device and insertion of the cannula;
[0039] FIG. 7 is a side view of an insertion device of the embodiment in FIG. 5 where the first insertion part and the second insertion part are assembled;
[0040] FIG. 8 is a side view of an insertion device of the embodiment in FIG. 5 where the first insertion part is disassembled from the second insertion part;
[0041] FIG. 9 is a side view of the first insertion part of an insertion device of the embodiment in FIG. 5 ;
[0042] FIG. 10 is another side view of the first insertion part of an insertion device of the embodiment in FIG. 5 ;
[0043] FIG. 11 is a side view of the insertion device of the embodiment in FIG. 5 where the first insertion part is placed in the second insertion part;
[0044] FIG. 12 is a side view of the insertion device of the embodiment in FIG. 11 where the first insertion part is rotated to the right;
[0045] FIG. 13 is a side view of the insertion device of the embodiment in FIG. 11 where the insertion device is in a position ready for activation and insertion of a cannula;
[0046] FIG. 14 is a side view of the insertion device of the embodiment in FIG. 11 where the insertion device is mounted in a receiver ready for insertion;
[0047] FIG. 15 is a side view of the insertion device of the embodiment in FIG. 11 where the insertion device is activated and insertion of a cannula is performed;
[0048] FIG. 16 is a side view of the insertion device of the embodiment in FIG. 11 where the insertion device is in a position after activation and insertion of a cannula and where the insertion needle is in a retracted position;
[0049] FIG. 17 is a side view of the first insertion part of the insertion device of the embodiment in FIG. 11 where the first insertion part is removed from the second insertion part for disposal.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0050] FIGS. 1 and 2 show a first embodiment of an insertion device according to the invention in a non-activated position. FIG. 1 shows the insertion device 1 , 2 in a not yet activated position and FIG. 2 shows the insertion device 1 , 2 in a position after having been activated and returned to the non-activated position.
[0051] The insertion device 1 , 2 shown in FIGS. 1 and 2 comprises a first insertion part 1 and a second insertion part 2 , which first insertion part 1 is formed like a cylindrical tube-piece being open in both ends and mounted slidably within the second insertion part 2 , the first insertion part 1 comprises guiding means in the form of a tap 7 moving in a slit 8 of the second insertion part 2 . The insertion device 1 , 2 further comprises an elastic element 3 for returning the first insertion part 1 to the non-activated position after activation, in the non-activated position the elastic element 3 is un-biased or only slightly biased. The insertion device 1 , 2 also comprises a needle-holding part 9 with an insertion needle 6 for inserting a cannula-holding part 5 which cannula-holding part 5 comprises a cannula 4 and a septum 5 a , into the skin of a patient. The insertion device 1 , 2 can be releasably connected to a receiver 11 in which receiver 11 the cannula-holding part 5 can be positioned and secured via hooks 12 on the receiver 11 engaging with recesses 13 formed in the cannula-holding part 5 . The receiver 11 is mounted on a base part 10 which base part 10 can be fastened to the patient's skin e.g. with an adhesive mounting pad.
[0052] The embodiment of FIGS. 1 and 2 is intended for single-use of the whole of the insertion device 1 , 2 . The embodiment makes it possible to first position the receiver 11 via a base plate 10 on the skin of the patient, thereafter to insert the cannula-holding part 5 of the insertion device 1 , 2 and to throw the insertion device 1 , 2 with the used insertion needle 6 away after insertion of the cannula-holding part 5 which can e.g. have the form of an infusion set. The insertion needle 6 is during injection never visible to the user and the surroundings are protected from the pointy needle.
[0053] According to the embodiment of FIGS. 1 and 2 the receiver 11 on the base plate 10 is shaped as an upright positioned cylindrical protrusion, the receiver 11 being for firmly positioning of the first insertion part 1 thereto as well as for receiving and fastening of the cannula-holding part 5 . The receiver 11 is fastened unreleasably to the base part 10 and can e.g. be either moulded together with the base plate 10 or fastened to the base plate 10 after the base plate 10 has been formed e.g. by gluing or welding. According to FIGS. 1 and 2 the base part 10 is illustrated as a relatively flat part but base part 10 could be any construction which makes it possible to unite the receiver 11 and the base part 10 into one unit which preferably can be worn by the user directly on the skin. The receiver 11 can be positioned on a peripheral part or a central part of the base plate 10 , to accommodate different injection angles for the cannula-holding part 5 . The cannula-holding part 5 can be inserted at an angle A deviating from 900 in relation to the distal surface of the base plate 10 , normally the angle A will be between 110° and 170° where the distal surface of the base plate 10 form one side of the angle and the inserted cannula 4 form the other side of the angle. In the embodiment of FIGS. 1 and 2 the receiver 11 is positioned centrally on the base plate 10 with an insertion angle A at 90°.
[0054] As shown in FIGS. 1 and 2 the receiver 11 is provided with fastening means comprising hooks 12 placed perpendicular to the upright cylindrical protrusion and parallel to the base plate 10 . The hooks 12 correspond to grooves or recesses 13 formed in the cannula-holding part 5 . The interaction between the recesses 13 of the cannula-holding part 5 and the hooks 12 of the receiver 11 on the base part 10 assures fastening of the cannula-holding part 5 to the receiver 11 after activation of the insertion device. When the cannula-holding part 5 and the receiver 11 after insertion are connected and fastened to each other they constitute e.g. a gateway for injection or an infusion part which can be joined to a connector part or a positioning part for e.g. of a delivery part comprising a reservoir and a pump.
[0055] As shown in FIGS. 1 and 2 the insertion device 1 , 2 is a two-part unit, where each unit can e.g. be constructed of a moulded body. The first insertion part 1 and the second insertion part 2 are both formed as cylindrical tubes, but other forms or profiles for the tube such as hexagonal, octagonal or the like can be used. On delivery this single-use equipment can either be jointed to the receiver 11 when delivered to the user in a sterile packing or it can be packed alone. If the single-use equipment is joined to the receiver 11 in a sterile packing, then the user will first unpack the joined device and prepare the base part 10 for fastening to the patients skin e.g. by removing a release liner from a mounting pad, then the user will secure the base plate 10 to the patients skin and finally the user will inject the cannula-holding part 5 and remove the insertion device 1 , 2 and dispose of this. If the single-use equipment is packed alone, the user will first unpack the insertion device 1 , 2 from the sterile packing, then place the insertion device against the patients skin e.g. in a receiver of a previously positioned base plate 10 and then finally the user will inject the cannula-holding part 5 and remove the insertion device 1 , 2 and dispose of the insertion device 1 , 2 which now has a contaminated insertion needle 6 .
[0056] The first insertion part 1 , which is positioned in the receiver 11 on the base plate 10 , and the second insertion part 2 engage with each other. The second insertion part 2 comprises the needle-holding part 9 carrying the insertion needle 6 for penetrating the skin of a patient and in this present single-use embodiment the second insertion part 2 actually constitutes the needle-holding part 9 . The cannula-holding part 5 which is carrying the soft cannula 4 is somehow secured to the needle-holding part 9 , normally just by friction between the insertion needle 6 and the soft cannula 4 . The insertion device 1 , 2 is further provided with an elastic element 3 which holds the two insertion parts 1 and 2 in position i.e. the elastic element 3 forces the first and the second insertion parts 1 , 2 into the non-activated position. In this embodiment the elastic element 3 is constituted of a helix metal spring, but the elastic element 3 may take any form, e.g. a rubber cylinder or the like that can force the first and second insertion parts 1 , 2 into the non-activated position. When the insertion device 1 , 2 is in the position before activation as shown in FIG. 1 , the elastic element 3 is unbiased and when the insertion device 1 , 2 is activated by manually pressing down the second insertion part 2 for insertion of the cannula-holding part 5 , then the elastic element 3 is biased.
[0057] As shown in detail in FIG. 3 , the exterior surface of the first insertion part 1 is provided with a protrusion formed as a cylindrical tap 7 positioned at a part of the exterior surface of the first insertion part 1 which is facing towards an inner surface of the second insertion part 2 . The tap 7 interacts with an opening in the form of a slit 8 in the second insertion part 2 , said slit 8 comprising three parts 8 a , 8 b and 8 c shaped essentially as an Z with a long part 8 b being almost parallel to the insertion direction, a short part 8 c being essentially perpendicular to the insertion direction and a short part 8 a being angled compared to the short part 8 c . When the tap 7 of the first insertion part 1 is placed in a locking position in the slit 8 , i.e. the tap is positioned at one of the short part 8 a and 8 c of the slit 8 , the insertion device is then locked in the insertion direction. If the elastic element 3 is slightly biased in the non-activated position then the tap 7 of the first insertion part 1 is forced into the most proximal end of the short part 8 a of the slit 8 . The first insertion part 1 of this embodiment provides a needle protector both before and after activation of the insertion device 1 , 2 .
[0058] FIG. 4A shows the same the single-use insertion device as shown in FIGS. 1 and 2 at an angle from above where the insertion device 1 , 2 is ready for activation, i.e. same position as in FIG. 1 . The flexible base plate 10 is provided with fastening means 14 for fastening of a delivery device (not shown) which delivery device can comprise e.g. both a reservoir for medication and a transporting means in the form of a pump or the like.
[0059] When activating the single-use insertion device 1 , 2 shown in FIGS. 1 , 2 and 4 , with the intend of fastening of a cannula-holding part 5 in the form of e.g. an infusion set, an injection part or a gateway 5 , 11 to the to the skin of the patient, the second insertion part 2 is first rotated around the longitudinal axis defined by the insertion direction in order to move the tap 7 from the short parts 8 a and 8 c of the slit 8 into the corner of the short part 8 c and the long part 8 b of the slit 8 thereby making it possible for the tap 7 to move in the longitudinal direction of the long part 8 b of the slit 8 . The second insertion part 2 is then manually pressed down towards the patient thereby biasing the spring 3 and at the same time the tap 7 move in the long part 8 b of the slit 8 towards the distal end of the second insertion part 2 , whereby the needle-holding part 9 and the cannula-holding part 5 is being moved, due to the pressing of the second insertion part 2 , simultaneously towards the skin of a patient. The insertion needle 6 penetrates the skin and the cannula is inserted into the patient when the insertion device enters into the fully activated position. As shown in FIG. 2 the hooks 12 of the receiver 11 engage with the recesses 13 of the cannula-holding part 5 thereby fastening the cannula-holding part 5 to the receiver 11 . When the cannula-holding part 5 is fastened to the receiver 11 , the pressure on second insertion part 2 is released by removing the manually applied pressure, leading to the spring 3 moving into an unbiased position thereby moving the tap 7 in the slit 8 toward the most proximal end of the slit 8 and at the same time moving the needle 6 into the interior of the first insertion part 1 . The second insertion part 2 is then rotated and the tap 7 moved into the short part 8 c of the slit 8 for locking the first 1 and second insertion part 2 and at the same time to keep the used needle 6 in place inside the insertion device 1 , 2 . This embodiment provides a single-use injection device 1 , 2 with needle protection, where the needle 6 is never visible to the user and which insertion device 1 , 2 can be thrown-away after use without the risk of injuries caused by a pointy needle.
[0060] FIG. 4B-F show other embodiments of the base part 10 and a corresponding cannula-holding part 5 correctly positioned by an injection device 1 , 2 according to the invention.
[0061] In FIG. 4B the peripheral placed receiver has a square profile in which a cannula-holding part 5 having a round profile is placed. In order to position this cannula holding part 5 correctly in the base part 10 an injection device 1 , 2 having a square outer and a round inner profile is needed or at least an inserter which have parts or surfaces adapted to fit into an outer square space formed by the receiver and have parts or surfaces which can provide a space in which a round cannula holding device can slide.
[0062] In FIG. 4C the peripheral placed receiver has a square profile in which a cannula-holding part 5 having a square profile is placed. In order to position this cannula holding part 5 correctly in the base part 10 an injection device 1 , 2 having a square outer and a square inner profile is needed or at least an inserter which have parts or surfaces adapted to fit into an outer square space formed by the receiver and have parts or surfaces which can provide a space in which a square cannula holding device can slide.
[0063] FIG. 4D shows a centrally placed receiver without upright walls guiding the inserter into position. Instead the slightly raised circumference of the central plate 10 a of the base part 10 corresponding to a part of the proximal end of the inserter indicates the correct position of the inserter during insertion of the cannula-holding part 5 .
[0064] FIG. 4E shows a base part 10 having a centrally placed receiver having upright walls which walls provide the receiver with a square profile. The base part is shown before the cannula-holding part 5 inserted.
[0065] FIG. 4F shows a centrally placed receiver 11 having a square profile in which a cannula-holding part 5 having a square profile is placed.
[0066] In another embodiment as shown in FIGS. 5 and 6 the insertion device 1 , 2 is intended for multiple-use. FIG. 5 show the insertion device 1 , 2 in a not yet activated position before insertion and FIG. 6 show the insertion device 1 , 2 in a position after activation, where the cannula is inserted.
[0067] As shown in FIGS. 5 and 6 the injection device 1 , 2 comprises a first insertion part 1 and a second insertion part 2 , which first insertion part 1 is mounted slidably within the second insertion part 2 with an elastic element 3 for keeping the first insertion part 1 and the second insertion part 2 in position and for activating the insertion device 1 , 2 , a cannula-holding part 5 provided with a cannula 4 and a septum 5 a , the cannula-holding part 5 being connected to a needle-holding part 9 , which needle-holding part 9 is provided with an insertion needle 6 for insertion of the cannula 4 into the skin of a patient. In this embodiment the needle-holding part 9 is a separate needle-holding part 9 being releasably fastened to the insertion part 2 by way of example a tongue and groove connection 9 a , 9 b . The insertion device 1 , 2 is releasably connected to a receiver 11 via hooks 12 on the receiver 11 engaging with recesses 13 formed in the cannula-holding part 5 , which receiver 11 is mounted on a base part 10 which base part 10 is fastened to the patient's skin. The base plate 10 is provided with fastening means 14 for fastening of a delivery device (not shown).
[0068] FIGS. 7 and 8 show in detail the interconnection of the two-unit insertion device 1 , 2 of the present invention intended for multiple-use. The first insertion part 1 is on the exterior surface provided with a protrusion formed as a cylindrical tap 7 positioned at a surface facing towards the second insertion part 2 . The tap 7 interacts with an opening in the form of a slit 8 in the second insertion part 2 , said slit 8 is shaped essentially as a stair with a long longitudinal part 8 b , a short longitudinal part 8 a and a transverse short part 8 c separating the two longitudinal parts 8 a and 8 b , the two longitudinal parts 8 a , 8 b being parallel and displaced from each other. The transverse short part 8 c can be provided with a not shown resting position for the tap 7 e.g. in the form of a depression in the proximal edge of the slit 8 c which depression should be wide enough for the tap 7 to fit into in order to make it necessary to press the two insertion parts together before it will be possible to move the tap either to the left or to the right. The short longitudinal part 8 a of the slit 8 forms an opening in the proximal edge of the second insertion part 2 ; the short longitudinal part 8 a thereby provides means for uniting or releasing the first insertion part 1 from the second insertion part 2 . This embodiment makes it possible to make the two units of the two-unit insertion device 1 , 2 interact thereby constituting a needle protector both before and after activation of the insertion device 1 , 2 for insertion of the cannula-holding device 5 .
[0069] When the insertion device 1 , 2 is assembled, the tap 7 of the first insertion part 1 is placed in the longitudinal slit 8 a of the second insertion part 2 and the first and the second insertion parts are pushed together until the tap 7 reaches corner between the longitudinal slit 8 z and the short transverse part 8 c of the slit 8 . Then the second insertion part 2 is rotated to the left placing the tap 7 in the short transverse part 8 c of the slit 8 thereby placing the insertion device in a locked position. The elastic element 3 is in this position unbiased or only slightly biased. The insertion device 1 , 2 is now ready for use. Likewise, the insertion device can be disassembled by reverse rotation of the second insertion part 2 , thereby moving the tap 7 from the short transverse part 8 c of the slit 8 into the short longitudinal slit 8 a and drawing the second insertion part 2 away from the first insertion part 1 causing the tap 7 to exit via the short longitudinal slit 8 a and thereby releasing the first insertion part 1 from the second insertion part 2 .
[0070] This embodiment makes it possible to remove and dispose of only the first insertion part 1 and the insertion needle 6 of the two-unit insertion device 1 , 2 thereby providing a possibility of repeated use of the second insertion 2 together with a new replaced first insertion part 1 containing a new insertion needle 6 . Furthermore, this embodiment makes it possible for the first insertion part 1 to constitute a needle protector both before and after activation of the insertion device 1 , 2 for insertion of the cannula-holding device 5 .
[0071] As shown in detail in FIGS. 9 and 10 , the first insertion part 1 of the present multi-use embodiment comprises the tap 7 for engaging with the second insertion part 2 and means in the form of a protruding tap 9 c which engages with an essentially L-shaped slit 7 a for locking and unlocking the needle-holding part 9 during insertion. The needle-holding part 9 comprises the insertion needle 6 (not shown), which needle-holding part 9 is fastened to the cannula-holding part 5 .
[0072] FIGS. 11-17 show the insertion device 1 , 2 when in use. FIG. 11 show the placing and assembling of a disposable first insertion part 1 into a reusable second insertion part 2 . The tap 7 of the first insertion part 1 is placed into the short longitudinal slit 8 a and moved up to the transverse short part 8 c , which part 8 c separates the short longitudinal slit 8 a from the long longitudinal slit 8 b in the stair-shaped slit 8 . The disposable first insertion part 1 comprises a needle-holding part 9 with an insertion needle 6 fastened to a cannula-holding part 5 . The needle holding part 9 is fixed in relation to the second insertion part 2 and a tap 9 c protruding from the exterior surface 1 of the needle-holding part 9 is engaged with slit 7 a of the first insertion part 1 , the protruding tap 9 c is placed in the short part of the L-shaped slit 7 a for securing a locking position of the needle-holding part 9 relative to the first insertion part 1 . This way, the insertion needle 6 is locked inside in the first insertion part 1 and kept safe and hidden to the patient.
[0073] In FIG. 12 , the first insertion 1 of the insertion device 1 , 2 is rotated towards the right thereby moving the tap 7 into the transverse slit 8 c separating the short longitudinal slit 8 a from the long longitudinal slit 8 b thereby securing the first insertion part 1 in a locked position in the longitudinal direction relative to the second insertion part 2 . The tap 9 c of the needle-holding part 9 is due to the rotation of the first insertion part 1 simultaneously being moved to the left into the short part of the L-shaped slit 7 a but the tap 9 c remains in a position where the needle-holding part 9 is locked in the longitudinal direction. The elastic element 3 for activating the insertion device 1 , 2 is in this position unbiased or slightly biased.
[0074] FIG. 13 show the placing of tap 7 at the end point of rotation of the first insertion part 1 . The tap 7 has reached the corner between the long longitudinal slit 8 b and the transverse slit 8 c and further rotation of the first insertion part 1 is not possible. The tap 9 c of the needle-holding part 9 is during the rotation of the first insertion part 1 simultaneously moved into the corner of the essentially L-shaped slit 7 a leaving the needle-holding part 9 in an unlocked position. The elastic element 3 for activating the insertion device 1 , 2 is still in an unbiased position. Thus, the insertion device 1 , 2 is left in a position ready for activation and insertion of the cannula 4 .
[0075] FIG. 14 shows the same insertion device 1 , 2 as FIG. 13 in a position ready for activation and insertion of the cannula-holding part 5 , where the insertion device 1 , 2 is mounted in a receiver 11 connected to a base plate 10 . The tap 7 is in an unlocked position in the corner between the long part 8 b of the slit 8 and the short transverse part 8 c.
[0076] FIG. 15 show the activation of the insertion device 1 , 2 . The second insertion part 2 is manually pressed down towards the patients skin, thereby biasing the elastic element 3 and the first insertion part 1 will slide into the second insertion part 2 . At the same time the manually pressure will cause tap 7 to slide in the long longitudinal slit 8 b of the second insertion part 2 and tap 9 c to slide in the longitudinal slit 7 a of the first insertion part 1 by which the insertion needle 6 and cannula 4 exits the first insertion part 1 , the insertion needle 6 penetrating of the patients skin and inserting the cannula 4 into the patient. The cannula-holding part 5 engages with the receiver 11 on the base plate 10 which assures fastening of the cannula-holding part 5 to the receiver 11 .
[0077] FIG. 16 show the insertion device 1 , 2 mounted in a receiver 11 , which receiver 11 is connected to a base plate 10 . The insertion device 1 , 2 is shown in a position after insertion of the cannula 4 into a patient. The manual pressure on the second insertion part 2 is released causing the elastic element 3 to move into an unbiased position, this causing the tap 7 to slide down in the long longitudinal slit 8 b to the transverse slit separating the short longitudinal slit 8 a from the long longitudinal slit 8 b , and the tap 9 c of the first insertion part 1 to slide up in the longitudinal slit 7 a . Thus, the elastic element 3 retracts the insertion needle 6 fastened to the needle-holding part 9 from the cannula-holding part 5 and into the first insertion part 1 leaving the cannula 4 within the patient. The second insertion part 2 is rotated to the left causing the tap 7 to move into the transverse part separating the two long and short longitudinal slits 8 a , 8 b , and causing tap 9 c to move into the short part if the essentially L-shaped slit 7 a , thereby locking both the first insertion part to the second insertion part and locking the needle-holding part 9 within the first insertion part 1 . The insertion device 1 , 2 is then to be safely removed from the receiver 11 , the insertion needle 6 being kept safely inside the first insertion part 1 and not visible to the patient.
[0078] FIG. 17 show the first insertion part 1 in a position after use, where the first insertion part 1 containing the used insertion needle 6 (not shown) is released from the second insertion part 2 for disposal. The needle-holding part 9 (not shown) is locked to the first insertion part 1 via the tap 9 c in the essentially L-shaped slit 7 a , thereby keeping the used insertion needle 6 (not shown) within the first insertion part 1 for safety reasons, when disposed of.
[0079] With the present multi-use embodiment, a used insertion needle can be both safely removed and disposed of after application. The used first insertion part can be replaced with a new first insertion part comprising a new needle and needle-holding part as well as a new cannula-holding part with a new cannula and assembled with the used second insertion part 2 . Thus, it is possible to reuse the second insertion part and only replace the first insertion part thereby saving expenses. | The invention relates to a device for insertion of a cannula of e.g. and infusion set for intermittent or continuous administration of a therapeutical 5 substance, such as e.g. insulin. The insertion device assures that before, during and after insertion the insertion needle is not visible to the patient. The insertion device according to the invention comprises a first insertion part ( 1 ) and a second insertion part ( 2 ), a cannula holding part ( 5 ) provided with a 10 cannula ( 4 ), and an injection needle ( 6 ) where—the second insertion part ( 2 ) is connected to the injection needle ( 6 ) and the injection needle ( 6 ) is releasably combined with the cannula ( 4 ) of the cannula holding part ( 5 ), —the first insertion part ( 1 ) covers the injection needle ( 6 ) in a non-activated 15 position and in an activated position the injection needle ( 6 ) projects beyond the first insertion part ( 1 ), —at least a part of the second insertion part ( 2 ) and the first insertion part ( 1 ) can be moved in relation to each other between at least one activated position and at least one non-activated position, 20 wherein the second insertion part ( 2 ) exceeds the distal end of the first insertion part ( 1 ) when the device is in an activated position. | 0 |
[0001] This is a division of U.S. patent application Ser. No. 09/788,151, filed Feb. 16, 2001, the entire specification of which is incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Technical Field
[0003] The present invention relates to methods and apparatus for separating solids from liquids and other solids and, in particular, to dewatering and decontaminating coal tailings, clean coal products, and mineral slurries. The present invention also relates to methods and apparatus for liquid purification and, in particular, to methods and apparatus for recovering decontaminated process water from coal tailings, clean coal products and mineral slurries.
[0004] 2. Background Information
[0005] In the cleaning or washing of coal for commercial use as a fuel and the like, the uncombustible ash content of coal is usually removed to enhance the heat content of the coal. Reduction in the ash content results in savings in transportation and ash disposal costs. Other materials frequently occurring with coals that may be removed in washing operations include various clays and sulfides. Such clays commonly include aericite (KAl 2 (AlSi 3 O) (OH) 12 , smectite (Al 2 Si 4 O 10 (OH 12 ) H 2 O, and kaolinite clays (Al 2 Si 4 O 5 (OH) 4 . Sulfides are usually pyrite (FeS 4 (isometrical)).
[0006] During the processing of coal to effect such washing, a coal refuse slurry is generated. This slurry comprises coal fines known as tailings, and contaminants such as clay and mud suspended in plant process water. Due to the high volume of water used in the processing of coal, it is necessary to reclaim the wash water for recirculation in the plant. The concentrated solids are sent to an impoundment pound for disposal. In some cases in which coal washing plants have been operating for years, such slurry pounds may occupy hundreds of acres and may contain millions of tons of coal fines. These slurry ponds may also contain coal slurry to a depth of 70-150 feet. Such slurry ponds not only occupy a great deal of valuable land, but they also contain a considerable amount of energy and water resources.
[0007] Clean coal slurries are also used as, for example, an effective and cost effective means for transporting coal over distances from the place of production to the place of use.
[0008] The prior art discloses various methods and apparatuses for dewatering and decontaminating refuse pond coal slurries and for dewatering clean coal slurries.
[0009] U.S. Pat. No. 4,128,474 to Ennis discloses a wet mechanical process for cleaning, upgrading and dewatering fine coal. The process provides for forming an aqueous feed slurry of fine coal and its associated contaminant particles wherein all particles have a particle portion size of less than about 6 mm. ranging to zero. The feed slurry is separated into coal slurry and refuse slurry portions in a spiral gravity concentrator by removing contaminants having a particle size greater than about 0.15 mm. The concentrated coal slurry is then fed to a hydrocyclone separator where all the ultra-fine silt material having a particle size of less than 0.15 mm. is removed and the coal particle fraction 6 mm. to 0.15 mm. is accumulated and thoroughly dewatered.
[0010] U.S. Pat. No. 4,257,879 to Bogenschneider, et al. discloses a coal slurry dewatering process in the fine grain content is regulated to keep the filter cake at a constant level. A separation of the slurry into a predominantly relatively fine grain fraction and a relatively coarse grain fraction, with the division point being between about 0.03 and 0.15 mm. is carried out with a formation if a coal agglomerate from the fine grain fraction is accomplished.
[0011] U.S. Pat. No. 4,526,121 to Shudo, et al. discloses a ship for treating a coal slurry comprising a pair of opposed trays disposed in the vicinity of the upper deck for causing the coal slurry supplied thereto to flow forward and delivering the slurry, a slanting dewatering screen disposed below each of the trays for dewatering the coal slurry delivered from the tray to separate a particulate coal fraction having relatively large particle sizes and conveyors for transporting to a specified position on the upper deck the particulate coal fraction dewatered and falling off the screen.
[0012] U.S. Pat. No. 4,620,672 to Liebson, et al. discloses a system for converting a coal slurry flowable through a pipeline to a coal water mixture capable of being rendered suitable for direct combustion in a boiler. The system includes a pipeline extending from a region adjacent to a mine or source of a coal to a region adjacent to a boiler or furnace at which combustion is to take place. In the furnace region, the slurry from the pipeline is directed into a holding space, such as a pond, from which it is directed to a grinding apparatus. On the way to the grinding apparatus from the pond, a side stream of the slurry is directed through a dewatering apparatus where the concentration of the side stream is increased from 50-55 weight percent of solids to about 70-80 weight percent of solids. The outlet of the dewatering apparatus is directed back to the main flow of slurry from the pond, and the main flow enters the grinding apparatus where the slurry is ground to a particle size suitable for combustion, such as 70-80 weight percent of solids at 200 mesh. The ground slurry can then be directed into a small agitated tank and from this tank it can be directed into the boiler or furnace for combustion.
[0013] U.S. Pat. No. 4,810,371 to Fonseca discloses a process for automating fine coal cleaning including monitoring the operation of a flotation cell for separating coal from ash impurities by automatically detecting the coal content of the tailings from the cell and controlling the supply of additives to the cell to optimize slurry coal recovery and automatically monitoring the fluid level of the coal slurry in a dewatering filter tub to control the supply of additives to the filter tub and functioning of a dewatering filter.
[0014] U.S. Pat. No. 5,236,596 to Greenwald, Sr. discloses a method and apparatus for dewatering an aqueous coal slurry which includes imparting high shear forces to the aqueous coal slurry in the presence of a peptizing agent to render coal particles hydrophobic by stripping clay from the coal particles and peptizing the clay in the aqueous medium of the slurry. The slurry is separated to recover coal particles and the aqueous medium is drained from the coal particles.
[0015] U.S. Pat. No. 5,256,169 to Roe discloses a process for dewatering and agglomerating fine coal. The process consists of treating an aqueous fine coal slurry with a chemical binding agent prior to filtration or drying. The preferred chemical binding agent is an emulsifiable process oil. Efficiencies in dewatering and in lower dustiness of the treated coal are disclosed.
[0016] U.S. Pat. No. 5,346,630 to Kenney discloses a process for the vacuum filtering of coal slurries. Dewatering of a filter cake is achieved by contacting the coal with a C(8) to C(20) aliphatic carboxylic acid or a derivative thereof, especially sodium oleate.
[0017] U.S. Pat. No. 5,476,522 to Kerr, et al. discloses a method for concentrating coal tailings and for dewatering coal products employing a copolymer of diallyldimethylammonium halide and a vinyl alkoxysilane, preferably a copolymer of diallyldimethylammonium chloride and vinyltrimethoxysilane as a coagulant. The method for concentrating coal tailings comprises steps of feeding the coal tailings to a thickener; treating the coal tailings with the coagulant, discharging substantially concentrated tailing; and withdrawing substantially clarified liquid from the thickener. A method for dewatering coal products containing water comprising the steps of feeding the clean coal containing water to a twin belt filter press; treating said coal with an effective amount of a copolymer coagulant of diallyldimethlylammonium halide and vinyl alkoxysilane, preferably diallyldimethlylammonium chloride and vinyl trimethoxysilane is also disclosed. The method encompasses removing water from the coal product through the addition of the subject polymer coagulant; removing the dewatered clean coal product from the filter; and withdrawing the recycled water through the filter.
[0018] U.S. Pat. No. 5,622,647 to Kerr, et al. discloses a method for dewatering coal tailings, clean coal products and mineral slurries, as well as for the clarification of water contained in coal refuse slurries, employing a copolymer of diallyldimethylammonium halide and a vinyl alkoxysilane, which is preferably a copolymer of diallyldimethylammonium chloride and vinyltrimethoxysilane as a coagulant.
[0019] U.S. Pat. No. 5,795,484 to Greenwald, Sr. discloses a method and apparatus for dewatering an ultra-fine coal particle fraction forms a coal product with particles that are dilatant due to the mechanical stripping of the clay contaminants from the coal surface and the subdividing of the clay to clay platelets which are peptized to maintain discreetness in an aqueous slurry. The coal particles are unflocculated and can produce an aqueously permeable barrier on a sieve. The ultrafine coal product has an increase of 100-150 BTU per pound and when combusted reduced Nox production of 20-40% is realized. In a 15×0 micron coal fraction, the sulphur content is significantly reduced.
[0020] U.S. Pat. No. 6,042,732 to Jankowski, et al. discloses a method for dewatering coal tailings, clean coal products and mineral slurries with an effective coagulating amount of a combination of a cationic polymer and a starch. A preferred cationic polymer is poly(dimethylaminoethylaerylate methyl chloride quaternary salt) and preferred starches are unmodified.
[0021] A need still exists for a further improved method and apparatus for dewatering and decontaminating coal tailings and recovering water therefrom.
[0022] A need also still exists for a further improved method and apparatus for dewatering and decontaminating clean coal slurry products and mineral slurries and reconveying process water therefrom.
SUMMARY OF THE INVENTION
[0023] It is an object of the present invention to provide an efficient and cost effective method and apparatus for dewatering coal tailings and for removing contaminants therefrom.
[0024] It is a further object of the present invention to provide an efficient and cost effective method and apparatus for dewatering substantially clean coal slurries and to remove any contaminants present therefrom.
[0025] It is a further object of the present invention to provide an efficient and cost effective method and apparatus for dewatering other mineral slurries and to remove any contaminants therefrom.
[0026] It is a further object of the present invention to provide an efficient and cost effective method and apparatus for reclaiming valuable water from coal refuse slurry ponds.
[0027] It is a further object of the present invention to provide an efficient and cost effective method and apparatus for reclaiming valuable process water from substantially clear coal slurry products.
[0028] It is a further object of the present invention to provide an efficient and cost effective method and apparatus for reclaiming valuable process water from other mineral slurries.
[0029] It is a further object of the present invention to provide an efficient and cost effective method and apparatus for reclaiming valuable land resources from land previously occupied by coal refuse slurry ponds.
[0030] It is a further object of the present invention to provide an efficient and cost effective method and apparatus for a ameliorating or eliminating any environmental risk to soils and water tables which may be presented by coal refuse slurry ponds.
[0031] It is a further object of the present invention to provide a method and apparatus for efficiently and cost effectively dewatering coal tailings and removing contaminants therefrom which is mobile and can readily be moved to coal refuse slurry ponds in remote, hilly or mountainous locations.
[0032] It is a still further object of the present invention to provide a method and apparatus for efficiently and cost effectively dewatering coal tailings and removing contaminants therefrom which is compact and adapted to being used on sites where the available land for such operations is limited or where such available land is located on hilly, mountainous or otherwise uneven terrains.
[0033] These and other objects of the present invention are provided by the method of the present invention, which is a method of dewatering a mixture of coal tailings, water and contaminants comprising the steps of (a) providing a tank having a base surface and introducing said mixture of coal, tailings, water, and contaminants to said tank and allowing said coal tailings to settle on said base surface, (b) removing the coal tailings from said base surface of said tank along with water and contaminants and then separating said water and at least some of said contaminants from said coal tailings wherein said separated contaminants are suspended in said separated water, (c) adding an agent selected from one or more of the group consisting of a coagulant and a flocculent to said water and suspended contaminants separated from the coal tailings in step (b), (d) allowing the agent added in step (c) to coagulate or flocculate with the suspended contaminants to form a coagulated or flocculated mass and a quantity of supernatant water, and (e) separating the coagulated or flocculated mass formed in step (d) from the quantity of supernatant water formed in step (d).
[0034] This coal slurry cleanup is unique in that it does not matter as to the size or volume of a pond. The system consists of a completely portable plant and can be moved from one location to another in a matter of days. It operates on air, hydraulics and electric generator, and can be put in very remote areas. A dredge is put into a slurry pond to pump the material. This material consists of coal, water, clay, mud, or whatever else may have been deposited. The dredge must be adequate in size to pump the volume of material and water needed to operate the plant. In most cases, a volume of 800 GPM to 1500 GPM will be required. This coal slurry cleanup consists of a method where a portable plant is assembled wherever coal slurry is found to be recoverable, normally where coal prep plants have been operating for a period of time. The slurry will then be brought to the plant and processed to where there will be a steady stream of coal from a discharge belt to a stockpile. A backflow of waste water will flow to a clarifier tank which will allow the clay, mud and other heavy materials to settle out. The heavy material will then be pumped to a hydraulic press where the water is separated from solids. The solids will then be discharged to a stockpile and the water will return to the pond for use or can be let into a water stream.
[0035] Also encompassed within the present invention is a method of dewatering substantially clean coal slurry products comprising the steps of (a) providing a tank having a base surface and introducing the substantially clean coal product into said tank and allowing fine coal to settle on said base surface, (b) removing the fine coal from said base surface of said tank along with water and contaminants and then separating said water and at least some of said contaminants from said fine coal wherein said separated contaminants are suspended in said separated water, (c) adding an agent selected from one or more of the group consisting of a coagulant and a flocculent to said water and suspended contaminants separated from the fine coal in step (b), (d) allowing the agent added in step (c) to coagulate or flocculate with the suspended contaminants to form a coagulated or flocculated mass and a quantity of supernatant water, and (e) separating the coagulated or flocculated mass formed in step (d) from the quantity of supernatant water formed in step (d).
[0036] Also encompassed within the present invention is a method of dewatering other mineral slurries comprising the steps of (a) providing a tank having a base surface and introducing said mineral slurry into said tank and allowing said mineral fines to settle on said base surface, (b) removing the mineral fines from said base surface of said tank along with water and contaminants and then separating said water and at least some of said contaminants from said coal tailings wherein said separated contaminants are suspended in said separated water, (c) adding an agent selected from one or more of the group consisting of a coagulant and a flocculent to said water and suspended contaminants separated from the mineral fines in step (b), (d) allowing the agent added in step (c) to coagulate or flocculate with the suspended contaminants to form a coagulated or flocculated mass and a quantity of supernatant water, and (e) separating the coagulated or flocculated mass formed in step (d) from the quantity of supernatant water formed in step (d).
[0037] Also encompassed within the present invention is an apparatus for use in processing a liquid and at least one solid particulate material mixed with in said liquid said apparatus comprising a tank having a front end and a rear end, a base surface and a peripheral wall, an input point positioned adjacent the rear end of the tank extending generally upwardly from and surrounding the base wall, an output point positioned adjacent the front end of the, a particle collection area positioned on the base surface beneath the input point, and means for conveying the particles extending from adjacent the particle collection area to the output point.
[0038] Also encompassed within the present invention is an apparatus for use in processing a liquid and at least one solid particulate material mixed with liquid. This apparatus includes a tank having a front rear end, a base surface and a lateral wall having an upper rim. An input point is positioned adjacent the rear end of the tank adjacent the upper rim of the tank. An output point is positioned adjacent the front end of the tank. A particle collection area is positioned on the base surface beneath the input point, and a particle conveyor means extends from adjacent the particle collection area to the output point. There is a means for separating particles and water removed from the tank, a means for adding a coagulant or flocculent to the water, a second tank directly connected to the first tank, and means for removing a coagulated or flocculated mass from clarified water.
[0039] Also encompassed within the present invention is an apparatus for reducing the concentration of a particulate material and a liquid. The apparatus has a flow cavity having an input opening for the liquid with suspended particulate material and a restricted output opening for particulate material. The flow cavity has at least one perforated wall having an outer surface from which liquid having a reduced concentration of particulate material is collected.
BRIEF DESCRIPTION OF THE DRAWINGS
[0040] The preferred embodiment of the invention, illustrative of the best mode in which applicant contemplated applying the principles, is set forth in the following description and is shown in the drawings and is particularly and distinctly pointed out and set forth in the appended claims.
[0041] [0041]FIG. 1 is a perspective view of the apparatus used in a preferred embodiment of the method of the present invention;
[0042] [0042]FIG. 2 is a detailed vertical cross sectional view of a preferred embodiment of the drag tank similar to the one shown in FIG. 1;
[0043] [0043]FIG. 3 is a top plan view of the drag tank apparatus shown in FIG. 2;
[0044] [0044]FIG. 4 is a cross sectional view through 4 - 4 in FIG. 3;
[0045] [0045]FIG. 5 is a cutaway front elevational view similar to the settling tank shown in FIG. 1;
[0046] [0046]FIG. 6 is a top plan view of the hydraulic press similar to the hydraulic press shown in FIG. 1;
[0047] [0047]FIG. 7 is a side elevational view of the hydraulic press shown in FIG. 6;
[0048] [0048]FIG. 8. Is a front elevational view of the hydraulic filter press shown in FIG. 6;
[0049] [0049]FIG. 9 is a detailed view of circle 9 in FIG. 8;
[0050] [0050]FIG. 10 is a detailed view of circle 10 in FIG. 6; and
[0051] [0051]FIG. 11 is a flow chart illustrating the method of dewatering coal tailings and slurries and removing contaminants therefrom in accordance with the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0052] Referring to FIG. 1 there is a pond 10 with coal fine washing tailings or “coal tailings” having dimensions from about 0.25 inch down to about 0.001 inch. Along with these coal tailings, there are contaminants which may include clay, silt, mud and pyrite. These coal tailings are removed from pond 10 by a dredge 12 along with water in line 14 to a tank 16 which is referred to herein at various points as a “drag tank”. Preferably, the amount of water in the mixture of fine coal, contaminants and water in line 14 is adjusted to from about 60 percent to about 90 percent by weight. The drag tank 16 has an input point 18 and is mounted on a truck mount 20 so as to be mobile. The tank 16 contains a water, fine coal and contaminant mixture 22 and has an output point 24 for removal of fine coal and contaminants mixed with water. The tank 16 also has a discharge trough 26 for removal of water 22 adjacent a rim 28 . There is a conveyor system 30 which extends from the output point 24 of the tank 16 to remove fine coal and water 32 to a centrifuge 34 . Preferably, the amount of water in the mixture of fine coal, contaminants and water 34 is from about 10 percent to about 40 percent by weight. This centrifuge 34 separates clean fine coal 36 and deposits this fine coal on a conveyor belt 38 for removal to a stored fine coal deposit 40 . Preferably the centrifuge is a model no. EBW-36 centrifuge manufactured by CMI, Inc. of St. Louis, Mo. which is preferably operated at from about 1800 RPM to about 4200 RPM. Those skilled in the art will appreciate that other equivalent means of separating particles from water such as a filter press, a screw press, a belt filter, or a screen may be substituted for the centrifuge 34 . It is believed, however, that the centrifuge 34 would be the preferred means of separating such fine coal from water since clay contaminants may tend to adhere to coal particles, and centrifuging the fine coal and water may create sufficient shear to remove the clay from the coal particles. Such clay, which may be in a platelet shape, may become suspended in the water once removed from coal particles. Extending from the centrifuge 34 there is a centrifuge output line 42 which removes water and contaminants to a settling tank 44 . A settling tank discharge line 46 removes water and suspended contaminants to a polymer addition tank 48 from where polymer addition tank output line 50 extends to the discharge trough 26 from the tank 16 by means of which a coagulating or flocculating agent is added to the water in discharge trough 26 . This coagulating or flocculating agent may be an anionic or cationic polymer or a nonionic emulsion polymer. Such flocculents are preferably introduced into the total amount of water being introduced to the clarifier tank in an amount of from about 2 percent to about 6 percent by weight. The polymer may also be used with a starch in the manner disclosed, for example, in the aforesaid U.S. Pat. No. 6,042,732 to Jankowski, et al. which also discloses suitable flocculent polymers for use in the method of this invention. Specific suitable flocculent polymers for use in the method of the present invention are also disclosed in the aforesaid U.S. Pat. Nos. 5,476,522 and 5,622,647 both to Kerr, et al. Inorganic coagulants which are known in the art such as alem and iron salts may also be used. The discharge trough 26 empties into a clarifier tank 52 at a tank input 54 . The clarifier tank 52 is set on a truck mount 58 to allow the clarifier tank 52 to be mobile. The clarifier tank 52 has three settling sections 60 , 62 and 64 which empty respectively into discharge lines 66 , 68 and 70 which connect to hydraulic filter press 72 . The hydraulic filter press 72 has a water output line 74 . The hydraulic filter press 72 also has a plurality of solid output apertures as at aperture 76 where clay and other contaminants 78 are outputted as solids onto conveyor belt 80 . The structure and operation of this hydraulic filter press 72 is essentially the same as the embodiment shown in FIGS. 6 - 10 and described in greater detail hereafter. While the centrifuge 34 , settling tank 44 , polymer addition tank 48 , and hydraulic filter press 72 are not shown with a trailer mount, it will be understood that these components of the entire assembly, along with their associated piping and belting systems, may be readily disassembled and loaded onto a trailer for transporting such components to remote operation sites. Such sites may be located in hilly, mountainous, or uneven terrain and the entire apparatus may be readily and quickly reassembled for operation in an area where only relatively small amounts of level land are available. In practice, it is found that the entire assembly may be transported to an operations site on from about 3 to 5 tractor trailer combinations. It is also found that the entire apparatus may be assembled for use on only about 5,600 to 15,600 square feet of relatively level land.
[0053] Referring to FIGS. 2 - 4 , another embodiment of the drag tank described is shown generally at numeral 82 . This tank has a pair of sidewalls 84 and 86 , a rear end wall 88 , front oblique walls 90 and 92 , a front end wall 94 , and a base wall 96 . The tank 82 also has a water and coal fine mixture input point 98 by means of which the mixture is added to water 100 in the tank 82 which is maintained beneath the rim 102 of the tank 82 by a water discharge ramp 104 . Directly beneath the water and coal fine input 98 there are collected fine coal 106 on a collection area 108 on the base wall 96 . There is a continuous conveyor chain 110 with a plurality of outwardly extending paddles as at paddle 112 for moving the collected fine coal 106 to a solids discharge point 114 . As an alternative to using the conveyor chain 110 , a conveyor belt may be used. As an alternative to using the paddles as at paddle 112 , scoop or shovel shaped devices may be used to move the collected fine coal 106 to the solids discharge point 114 . The continuous conveyor belt 110 moves on rollers 116 , 118 , 120 , 122 , 124 , 126 , 128 , and 130 . In parallel spaced relation to the conveyor belt is a central ramp 132 which is angled upwardly and has a terminal downwardly angled section 134 . Preferably the angle of this central ramp 132 will be from about 20° to about 40° above the horizontal. Referring particularly to FIG. 4, it will be seen that the sidewalls 84 and 86 have inwardly sloped sections 136 and 138 respectively. Preferably the side walls 84 and 86 from angled inwardly from the vertical by from about 40° to about 60°.
[0054] Referring to FIG. 5, another embodiment of the clarification tank is shown generally at numeral 140 which includes a tank input line 142 and a tank output line 144 . In this embodiment, there are four settling sections 146 , 148 , 150 , and 152 . These settling sections have high floc density areas 154 , 156 , 158 , and 160 . Above these high floc density areas there is a clarified supernatant water area 162 . The settling sections are respectively discharged in lines 164 , 166 , 168 , and 170 . The concentration of floc will be greatest in settling section 146 , and will decrease from section 148 to section 150 , wherein the floc concentration will be the lowest in section 152 . It will be appreciated that more of fewer settling sections may be used to optimize results in particular situations.
[0055] Referring to FIGS. 6 - 10 , another embodiment of the hydraulic filter press element is shown generally at numeral 172 which has an input side 174 and a discharge side 176 . On the input side 174 there are input line connections 178 , 180 , 182 , and 184 . Adjacent the input side 174 there is a transverse trough 186 from which a water discharge line 188 extends for discharge of purified water from the system. The hydraulic filter press 172 also has lateral walls 190 and 192 , and longitudinal troughs 194 , 196 , 198 , 200 , 202 , 204 , 206 , and 208 are interposed. Extending between the lateral walls 190 and 192 there is a transverse wall 210 . On the discharge side 176 of the hydraulic filter press 172 , there are restricted output apertures 212 , 214 , 216 , 218 , 220 , 222 , 224 , and 226 . The hydraulic filter press 172 also has a base wall 228 and a top wall 230 . The hydraulic filter press 172 is supported by piston and cylinder combination 232 which rests on a base 234 and is connected to a axle 236 . At its opposed side the hydraulic filter press 172 is supported by piston and cylinder combination 238 which is mounted on a base 240 and attached to an axle 242 . These piston and cylinder combinations 232 and 238 cooperatively adjust the height of the hydraulic filter press 172 from a lowered position as shown in solid lines and to an elevated inclined position as is shown at 172 ′ in phantom lines in FIG. 7. The angle of inclination of the position of the elevated hydraulic position of hydraulic filter press 172 will be in the range of 0° to about 40° and depending on the concentration of the particles in the water often more preferably in the range of about 20° to about 40°.
[0056] The hydraulic filter press 172 includes a flow cavity 244 which is bonded by the bottom wall 228 , the top wall 230 , side wall 246 , side wall 248 , front wall 250 and rear wall 252 . The top wall 230 has a perforated section 254 with a plurality of vertical perforations connecting to the flow cavity 244 . Such perforations are shown as, for example, perforations 256 and 258 in FIG. 10. Preferably, these perforations are circular and about one inch in diameter and are separated from each other by about ¼ inch so that there are about 108 perforations per square foot on the perforated section 254 of top wall 230 . Positioned in parallel arrangements perpendicularly to wall 230 there are a plurality of longitudinal walls 262 , 264 , 266 , 268 , 270 , 272 , and 274 which define longitudinal troughs 194 , 196 , 198 , 200 , 202 , 204 , 206 , and 208 . Referring particularly to FIG. 9, it will be seen that the top wall 230 is comprised of a rigid top section 276 , a rigid bottom section, 278 and a medial textile section 280 which is preferably comprised of a woven synthetic material. It will also be seen that there are perforations as at perforation 282 in the top section 276 and perforations as at perforation 284 in the bottom section. Each perforation in the top section as at perforation 282 is vertically aligned with another perforation as at perforation 284 in the bottom section 278 . The transverse end trough 186 is comprised of a front wall 286 , a rear wall 288 , end wall 290 , end wall 292 , and base wall 294 . It will be appreciated that the trough has an open top side. There is a gap 296 between the bottom of the front wall 286 and the top wall 230 of the flow cavity 244 . Because of this gap 296 , water flows from longitudinal troughs 194 , 196 , 198 , 200 , 202 , 204 , 206 , and 208 into the transverse trough 186 and is then outputted through line 188 . It will also be seen that there are transverse pipes 298 , 300 , 302 , and 304 for conveying water and suspended particles respectively from input line connections 178 , 180 , 182 and 184 to flow cavity 244 . Positioned in the flow cavity 244 there is also a movable plunger 306 which includes a head 308 and an extendable rod 310 . There are apertures 312 , 314 , 316 , and 318 through the head 308 to allow water with suspended particles to pass from the rear to front side of the head 308 . The plunger 306 would be extendable to move particles to the front wall 250 of the flow cavity 244 . It will be understood that ordinarily the use of this plunger would be optional and that in many situations water and suspended particles will move to the front wall 250 merely by applying sufficient pressure from the rear wall 252 . It will also be understood that the angle of inclination of the filter press can be selected to most efficiently remove the particles from the water. It will also be appreciated that greater angles of inclination will ordinarily be required when the concentration of particulate matter in the water increases while at low concentrations it may be possible to use a 0° inclination. It will be appreciated that other equivalent means of separating the floc from the water such as a centrifuge, a screw press, a belt filter, or a screen could, within the scope of this invention, be substituted for the filter press 172 .
EXAMPLE
[0057] A mixture of water and fine coal as well as clay, silt, mud, and pyrite contaminants are removed from a coal refuse slurry pond resulting from an industrial coal washing operation. This coal refuse slurry pond contained coal tailings from the No. 4 and No. 5 Upper Kittanning and Middle Kittanning seams mined in Tuscarawas County, Ohio. The mixture was removed from the coal refuse slurry pond by means of a 8 inch perforated dredge at the rate of 1,200 gallons/minute. This mixture of water, fine coal and contaminants varied from about 60-80% by weight water. The fine coal in this mixture varied from about 0.25 inch down to about 0.001 inch. A typical sample of this input mixture of coal tailings, contaminants and waterwas recovered and analyzed as recovered and after drying. The results of this analysis are shown in Table 1, wherein the ASTM method of analysis for each material is indicated adjacent the material and all reported percentages are percent by weight. The coal tailings, contaminant and water mixture was moved in a 8 inch diameter pipe at a speed of 1200 gallons/minute over a distance of 500 feet to the input point of a drag tank generally as shown in FIGS. 2 - 4 above. In this drag tank the chain conveyors had flights that were 12 inches high and 24 inches wide inset at the bottom of the tank. The tank was approximately 8 feet wide and 18 feet long at water level and had a capacity of 80 gallons. The conveyor continued above water level so at least 10 feet of conveyor was used to dewater the coal before it was discharged. The tank was approximately 8 feet in depth at its rear end. The chain conveyor was operated at a speed of 10 feet/minute. The water discharge trough at the rear end of the tank was 6 feet wide and 10 inches deep at the rim of the rear end of the tank. Partially dewatered fine coal along with contaminants were removed by the conveyor from the drag tank at a rate of about 8 tons/hour (266 pounds/minute) to an EB-48 centrifugal dryer which was procured from CMI, Inc. of St. Louis, Mo. Before being introduced to the centrifuge, this mixture of fine coal, contaminants and water had a water content of about 80 percent by weight. The centrifugal dryer was operated at a rate of 2,600 RPM to allow the fine coal to fluff out and be discharged to a conveyor belt at a rate of about 8 tons/hour (266 pounds/minute). Water effluent with suspended contaminants was removed from the centrifugal dryer at a discharge pipe at a rate of 10 gallons/minute to a 1,000 gallon capacity settling tank. Water along with settling contaminants were removed from this settling tank at a rate of 4 gallons/minute to a polymer addition tank where CALGON POL-E-Z 652 nonionic emulsion polymer which is commercially available from Nalco Chemical Company located at Naperville, Ill. so that the overall amount of polymer used in the water and contaminants introduced to the clarifier was 3% by weight. Water along with suspended contaminants and the added polymer are then moved to the tank discharge trough at a rate of 1,100 gallons/minute and added to the water being removed from the discharge tank and the water, contaminants and polymers were then added to the clarifier tank at a rate of 1,100 gallons/minute. The clarifier tank had a length of 10 feet and a capacity of 500 gallons and was similar to that shown in FIG. 5 above. Clarified supernatant water was removed from the tank outlet type at a rate of 30 gallons/minute. Floc and water were removed from each of the settling sections of the tank at a rate of about 4 pounds/minute to a hydraulic filter press by a 3 inch diaphragm pump operated by air. The hydraulic filter press was similar to the one shown in FIGS. 6 - 10 . The overall length of this hydraulic filter press was 11 feet whereas the longitudinal troughs were 10 feet in length and 1 foot in width. The overall width of the hydraulic filter press was 8 feet. The overall height of the filter press was 18 inches while the height of the longitudinal troughs of 12 inches. The metal insert for the hydraulic press serves as a strainer and was made of ¼ inch punch plate which was kept 2 inches from all sides and the bottom so that the water can easily discharge to the clear water. On the inside of the ¼ inch punch plate, a polyester and vinyl textile material 5 was held to the sides with plastic strips. The hydraulic filter press was positioned horizontally, i.e. with a 0° incline between its input and output ends. The hydraulic plunger was lined on the outside ends with a tube filled with grease so that it could clean the cloth and not tear. The plunger operated only when the press no longer took in material from the 3 inch diaphragm pumps. The plunger then pushed and caused the water left in the insert to discharge leaving dry solid clay and dirt to be removed to the stock pile area. Removal to the stock pile area was accomplished on discharge belts which was 24 inches wide and approximately 20 feet long at a rate of 4 pounds/minute. The purified water discharged from both the hydraulic filter press and the clarifier tank was found to be substantially free of both fine coal and suspended clay and other contaminants. Atypical sample of the moist solid output material was recovered and analyzed as recovered and after drying. The results of this analysis are shown in Table 2 wherein the ASTM method of analysis for each material is indicated adjacent to the material and all reported percentages are percent by weight. For the purposes of this disclosure, “ash” is considered to be the solid incombustible material present within the meaning of the cited ASTM method.
TABLE 1 Material As Recovered After Drying ASTM Method Moisture 32.34% — D-2961 M, D-3173 Ash 29.07% 42.96% D-3174 Sulfur 1.80% 2.66% D4239 Heat Content 4.987 BTU/lb 7,371 BTU/lb D-1989
[0058] [0058] TABLE 2 Material As Received After Drying ASM Method Moisture 13.00% — D-2961 M, D-3173 Ash 9.27% 10.66% D3174 Sulfur 2.00% 2.30% D-4239 Heat Content 10,918 BTU/lb 12,550 BTU/lb D-1989
[0059] Those skilled in the art will appreciate that the method and apparatus described herein may be used to dewater substantially clean coal slurry products which are used in the art to transport fine coal from the point of production to the point of use. It will also be understood that the method and apparatus of the present invention will have the advantage of removing a residual portion of any solid contaminants which may be present in the coal slurry product so that such contaminants are not present in either the fine coal or the process water recovered from the coal slurry product.
[0060] In addition to the treatment of fine coal, dewatering is also necessary in other areas of mineral processing. Those skilled in the art will appreciate that the method and apparatus of the present invention may be used to dewater and/or decontaminate a variety of such mineral slurries. Non-limiting examples of such slurries include sand and gravel, slurries of limestone, and ores, including, for example, taconite, trona, and titania. Guidance to those of ordinary skill in the art in coagulating or flocculating specific materials is contained, for example, in Coagulation and Flocculation. Theory and Applications, edited by Bohuslav Dobias, University of Regensburg, Regensburg, Germany (published by Marcel Dekker, Inc., New York, 1993), particularly at pages 126-137, which is incorporated herein by reference.
[0061] The term “particle” as it is used herein, means any small piece of a solid material, wherein that material may be one which is referred to as a particulate material as well as those materials which may be otherwise referred to in the art as a fine, powdered, pulverized, fragmented, or granular material or by like terms. For the purposes of this disclosure, a “particulate material” is a material comprised at least in part of particles.
[0062] The term “suspended” as it is used herein refers to the condition of a particle of a certain material or group of materials as being mixed within a liquid in a generally dispersed manner. The fact, however, that some particles of a material are heavier than other particles of the same material and may tend, therefore, to collect nearer the bottom of a liquid body than such lighter particles, is not intended to mean that the overall group of particles of the material does not fall within this definition.
[0063] The term “slurry”, as it is used herein, means any free flowing or flowable suspension of particles in a liquid. It is not intended that a mixture of particulate material and a liquid should be excluded from this definition merely because of the existence of a minor proportion of oversized particles in this mixture.
[0064] It will be appreciated that the method and apparatus described in this application is a simple and cost effective means for treating water and fine coal and contaminants found in tailing ponds from commercial coal washing operations. Water at ambient pressure which is substantially free of both fine coal and clay and other contaminants is recovered. Substantial amounts of dry, combustible fine coal are also recovered.
[0065] It will also be appreciated that the present invention provides an efficient and cost effective method and apparatus for dewatering substantially clean coal slurries and removing any contaminants present therefrom.
[0066] It will also be appreciated that the present invention provides an efficient and cost effective method and apparatus for dewatering other mineral slurries and removing any contaminants therefrom.
[0067] It will also be appreciated that the present invention provides an efficient and cost effective method and apparatus for reclaiming valuable process water from substantially clean coal slurry products.
[0068] It will also be appreciated that the present invention provides an efficient and cost effective method and apparatus for reclaiming valuable process water from other mineral slurries.
[0069] It will also be appreciated that the present invention provides an efficient and cost effective method and apparatus for reclaiming valuable land resources from land previously occupied by coal refuse slurry ponds.
[0070] It will also be appreciated that the present invention provides an efficient and cost effective method and apparatus for a ameliorating or eliminating any environmental risk to soils and water tables which may be presented by coal refuse slurry ponds.
[0071] It will also be appreciated that the present invention provides a method and apparatus for efficiently and cost effectively dewatering coal tailings and removing contaminants therefrom which is mobile and can readily be moved to coal refuse slurry ponds in remote, hilly or mountainous locations.
[0072] It will also be appreciated that the present invention provides a method and apparatus for efficiently and cost effectively dewatering coal tailings and removing contaminants therefrom which is compact and adapted to being used on sites where the available land for such operations is limited or where such available land is located on hilly, mountainous or otherwise uneven terrains.
[0073] Accordingly, the improved METHOD AND APPARATUS FOR DEWATERING COAL TAILINGS AND SLURRIES AND REMOVING CONTAMINANTS THEREFROM is simplified, provides an effective, safe, inexpensive, and efficient device which achieves all the enumerated objectives, provides for eliminating difficulties encountered with prior devices, and solves problems and obtains new results in the art.
[0074] In the foregoing description, certain terms have been used for brevity, clearness, and understanding; but no unnecessary limitations are to be implied therefrom beyond the requirement of the prior art, because such terms are used for descriptive purposes and are intended to be broadly construed.
[0075] Moreover, the description and illustration of the invention is by way of example, and the scope of the invention is not limited to the exact details shown or described.
[0076] Having now described the features, discoveries, and principles of the invention, the manner in which the METHOD AND APPARATUS FOR DEWATERING COAL TAILINGS AND SLURRIES AND REMOVING CONTAMINANTS THEREFROM is practiced, constructed and used, the characteristics of the construction, and the advantageous new and useful results obtained; the new and useful structures, devices, elements, arrangements, parts, and combinations are set forth in the appended claims. | A method of dewatering a mixture of coal tailings, water and contaminants comprising the steps of (a) providing a tank having a base surface and introducing said mixture of coal, tailings, water, and contaminants to said tank and allowing said coal tailings to settle on said base surface, (b) removing the coal tailings from said base surface of said tank along with water and contaminants and then separating said water and at least some of said contaminants from said coal tailings wherein said separated contaminants are suspended in said separated water, (c) adding an agent selected from one or more of the group consisting of a coagulant and a flocculent to said water and suspended contaminants separated from the coal tailings in step (b), (d) allowing the agent added in step (c) to coagulate or flocculate with the suspended contaminants to form a coagulated or flocculated mass and a quantity of supernatant water, and (e) separating the coagulated or flocculated mass formed in step (d) from the quantity of supernatant water formed in step (d). An apparatus for practicing the method is also enclosed. A similar method and apparatus for dewatering and recovering process water from substantially clean coal slurry products and mineral slurries is also disclosed. | 2 |
CROSS REFERENCE TO RELATED APPLICATIONS
This application claims the benefit of U.S. Provisional Application No. 61/885,804, filed Oct. 2, 2013. The contents of the referenced application are incorporated into the present application by reference.
BACKGROUND OF THE INVENTION
A. Field of the Invention
The invention generally concerns photocatalysts that can be used to produce hydrogen from water in a photocatalytic reaction. The photocatalysts include a photoactive material that is capable of absorbing light, which can then excite an electron from the valence band (VB) to the conductive band (CB) and use the excited electron to split water and produce hydrogen. The photoactive material includes a photonic band gap (PBG) that is tuned with or partially overlaps with its electronic band gap (EBG), thereby reducing the likelihood of the excited electron reverting back to its non-excited or ground state and therefore increasing its photocatalytic activity.
B. Description of Related Art
Hydrogen production from water offers enormous potential benefits for the energy sector, the environment, and the chemical industry. While methods currently exist for producing hydrogen from water, many of these methods can be costly, inefficient, or unstable. For instance, photoelectrochemical (PEC) water splitting requires an external bias or voltage and a costly electrode (e.g., Pt-based) for electrolysis of water.
With respect to photocatalytic electrolysis of water from light sources, while many advances have been achieved in this area, most materials are either unstable under realistic water splitting conditions or require considerable amounts of other components (e.g., large amounts of sacrificial hole or electron scavengers) to work, thereby offsetting any gained benefits. By way of example, a semiconductor photocatalyst is a material that can be excited upon receiving energy equal to or higher than its electronic band gap. Upon photo-excitation electrons are transferred from the valence band (VB) to the conduction band (CB) resulting in the formation of an electron (in the CB) and a hole (in the VB). In the case of water splitting, electrons in the CB reduce hydrogen ions to H 2 and holes in the VB oxidize oxygen ions to O 2 . One of the main limitations of most photocatalysts is the fast electron-hole recombination; a process that occurs at the nanosecond scale, while the oxidation-reduction reactions are much slower (microsecond time scale). Over 90% of photo-excited electron-hole pairs disappear before reaction by radiative and non-radiative decay mechanisms (Yamada, et al., 2009).
SUMMARY OF THE INVENTION
A solution to the aforementioned inefficiencies surrounding current water-splitting photocatalysts has been discovered. In particular, the solution resides in using electrically conductive materials (e.g., metal) in combination with a photoactive material that has a photonic band gap (e.g., an inverse opal structure or photonic crystal) that is tuned with or at least partially overlaps with its electronic band gap. Without wishing to be bound by theory, it is believed that overlapping of the photonic band gap with the electronic band gap reduces the likelihood that an excited electron would spontaneously revert back to its non-excited state (i.e., the electron-hole recombination rate can be reduced or suppressed). In particular, the photonic band gap of the photoactive material is believed to be a frequency range in which photons are unable to travel through the material. Therefore, when an electron moves from a given VB to a given CB (e.g., excitation through absorption of light), the electron will be restrained from spontaneously moving back to the VB, as the spontaneous emission of a photon that is typically associated with such a move from the CB to the VB would be at a frequency that is restricted due to the material's photonic band gap. The electron will remain in the CB for a longer period of time, which can result in use of said electron to split water rather than moving back to its VB (i.e., the electron-hole pair remains in existence for a longer period of time). This, coupled with the electrically conductive material deposited on the photoactive material, provides for a more efficient use of the excited electrons in water-splitting applications. Further, this improved efficiency allows for a reduced reliance on additional materials such as sacrificial agents as well as electrically conductive materials, thereby decreasing the complexity and costs associated with photocatalytic water-splitting systems.
A further discovery in the context of the present invention, with titanium dioxide being used as the photoactive material, is that the combination of anatase and rutile phases of titanium dioxide can further improve the efficiency of the photocatalysts of the present invention. In particular, it was discovered that the photonic band gap/electronic band gap overlap in combination with a mixture of anatase phase and rutile phase titanium dioxide can result in an increase in hydrogen production yield from water. Preferably, the titanium dioxide includes at least 80 wt. % anatase phase, and most preferably about 82.8 wt. % to about 90.2 wt. % anatase phase and 17.2 wt. % to about 9.8 wt. % rutile phase.
In one aspect of the present invention there is a photocatalyst that includes a photoactive material comprising a photonic band gap and an electronic band gap, wherein the photonic band gap that is tuned with or at least partially overlaps with the electronic band gap; and an electrically conductive material deposited on the photoactive material (e.g., it can be deposited on at least part of the surface of the photoactive material). “Tuned with” or “coincides with” means the photonic band gap range is identical with or substantially identical with (e.g., 95% or more) the electronic band gap range (e.g., 95% or more the same). “Partially overlaps with” means that at least a portion of the photonic band gap range overlaps with the electronic band gap range or is broader and completely encompasses the electronic band gap range. In particular aspects, the photoactive material has a three-dimensional structure, such as an inverse opal or photonic crystal structure. The inverse opal structure can be a closed-cell or open-cell structure. The photo-active material is such that it includes an electronic band gap where irradiation with light can excite an electron from its valence band to its corresponding conductive band. Non-limiting examples of such materials include semi-conductive materials such as TiO 2 , ZnO, CeO 2 , ZrO 2 , SrTiO 3 , CaTiO 3 , and BaTiO 3 , or mixtures thereof (e.g., composite semiconductors such as TiO 2 /CeO 2 , TiO 2 /ZrO 2 ). In particular instances, the photoactive material includes titanium dioxide such as titanium dioxide anatase, rutile, brookite or mixtures thereof such as anatase-rutile, anatase-brookite, or brookite-rutile, with a mixture of anatase phase to rutile phase being preferred. In one instance, the photoactive material comprises at least 80 wt. % anatase phase. In a particular embodiment, the photoactive material comprises about 82.8 wt. % to about 90.2 wt. % anatase phase and 17.2 wt. % to about 9.8 wt. % rutile phase. In certain instances, the photonic band gap ranges from 350 nm to 580 nm and the electronic band gap ranges from 360 to 430 nm. The electrically conductive material can be any material that conducts electricity in an efficient manner such as metal or non-metals (carbonaceous materials such as carbon nanostructures). In particular instances, the conductive material is a metal such as gold, ruthenium, rhenium, rhodium, palladium, silver, osmium, iridium, platinum, or combinations thereof. One particular combination that was identified as being particularly efficient in water-splitting applications is gold and palladium. The gold/palladium combination can be such that nanoparticles of palladium are deposited on the support as well as on the nanoparticles of gold. The electrically conductive material deposited on the photoactive material can be a plurality of nanostructures such as nanoparticles. The average size of such nanoparticles can be from 1 to 100 nm or from 1 to 50 nm or from 1 to 25 nm or from 1 to 10 nm. The amount of conductive material that can be deposited onto the photoactive material can vary as desired. In particular embodiments, it was found that low amounts of conductive materials can be used and still efficiently split water and create hydrogen gas. Such amounts can be less than 5, 4, 3, 2, 1 wt. % or less of the total weight of the photocatalyst. In some instances, the amount can be 0.001 wt. % to 5, 4, 3, 2, or 1 wt. % or from 0.001 wt. % to 0.1 wt. %. Also, the conductive material can cover from about 0.001 to 5% of the total surface area of the photoactive material and still efficiently produce hydrogen from water. The photocatalyst can be in particulate or powdered form and can be added to water. With a light source, the water can be split and hydrogen and oxygen gas formation can occur. In particular instances, a sacrificial agent can also be added to the water so as to further prevent electron/hole recombination. Notably, the efficiency of the photocatalyst of the present invention allows for one to avoid using or to use substantially low amounts of sacrificial agent when compared to known systems. In one instance, 0.1 to 5 vol. % of the photocatalyst and/or 0.1 to 5 g/L % of the sacrificial agent can be added to water. Non-limiting examples of sacrificial agents that can be used include methanol, ethanol, ethylene glycol propanol, iso-propanol, n-butanol, iso-butanol, ethylene glycol, propylene glycol, glycerol, or oxalic acid, or any combination thereof. In particular aspects, ethanol is used or ethylene glycol is used or a combination thereof. The photocatalyst can be self-supported (i.e., it is not supported by a substrate) or it can be supported by a substrate (e.g., glass, polymer beads, metal oxides, etc.). As noted above, the photocatalysts of the present invention are capable of splitting water in combination of a light source. No external bias or voltage is needed to efficiently split said water. In one non-limiting embodiment, the photocatalyst is capable of producing hydrogen gas from water at a rate of 1×10 −3 to 1×10 −7 mol/g Catal min.
Also disclosed is a system for producing hydrogen gas and/or oxygen gas from water. The system can include a container (e.g., transparent or translucent containers or opaque containers such as those that can magnify light (e.g., opaque container having a pinhole(s)) and a composition that includes photocatalyst of the present invention, water, and optionally a sacrificial agent. The container in particular embodiments is transparent or translucent. The system can also include a light source for irradiating the composition. The light source can be natural sunlight or can be from a non-natural source such as a UV lamp. As noted above, the system does not have to include an external bias or voltage.
In another embodiment, there is disclosed a method for producing hydrogen gas and/or oxygen gas from water, the method comprising using the aforementioned system and subjecting the composition to the light source for a sufficient period of time to produce hydrogen gas and/or oxygen gas from the water. The hydrogen gas and/or oxygen gas can then be captured and used in other down-stream processes such as for ammonia synthesis (from N 2 and H 2 ), for methanol synthesis (from CO and H 2 ), for light olefins synthesis (from CO and H 2 ), or other chemical production processes that utilize H 2 etc. In one non-limiting aspect, the method can be practiced such that the hydrogen production rate from water is 1×10 −3 to 1×10 −7 mol/g Catal min with a light source having a flux of about 0.1 mW/cm 2 and 30 mW/cm 2 .
Also contemplated is a method of modifying existing photocatalysts that have a photonic band gap material by modifying the photonic band gap to coincide with or at least partially overlap with the electronic band gap of said material. The photonic band gap can be tuned or modified as needed by modifying the pore size of the photonic band gap material (e.g., inverse opal). In one aspect, increasing the pore size can result in an increase in the photonic band gap.
In a further aspect, there is disclosed a method for tuning the photonic band gap of the photoactive material of the present invention by re-orienting the orientation of the material with respect to the light source (or vice versa) such that the photonic band gap is tuned to coincide with or at least partially overlap with the electronic band gap of said material. Because the photonic band gap changes with both its packing structure and incident light angle it is poised to work with increased efficiency during day light (for example a (111) orientated material with macro-pore diameter D=200 nm has its photonic band gap decreasing from 450 nm to 360 nm with increasing the incident light angle from about 20° C. to 60° C.).
In yet another aspect of the present invention, embodiments 1 to 37 are disclosed. Embodiment 1 is a photocatalyst comprising: a photoactive material comprising a photonic band gap and an electronic band gap, wherein the photonic band gap at least partially overlaps with the electronic band gap; and an electrically conductive material deposited on the photoactive material. Embodiment 2 is the photocatalyst of embodiment 1, wherein the photoactive material has an inverse opal structure. Embodiment 3 is the photocatalyst of embodiment 2, wherein the photoactive material comprises titanium dioxide. Embodiment 4 is the photocatalyst of embodiment 3, wherein the titanium dioxide comprises a mixture of anatase and rutile. Embodiment 5 is the photocatalyst of embodiment 4, wherein the titanium dioxide comprises at least 80 wt. %. Embodiment 6 is the photocatalyst of embodiment 5, wherein the titanium dioxide comprises about 82.8 wt. % to 90.2 wt. % anatase and 17.2 wt. % to 9.8 wt. % rutile. Embodiment 7 is the photocatalyst of any one of embodiments 3 or 6, wherein the photonic band gap ranges from 350 nm to 420 nm and the electronic band gap ranges from 360 to 430 nm. Embodiment 8 is the photocatalyst of any one of embodiments 1 to 7, wherein the electrically conductive material comprises a metal. Embodiment 9 is the photocatalyst of embodiment 8, wherein the metal is gold, ruthenium, rhenium, rhodium, palladium, silver, osmium, iridium, platinum, or combinations thereof. Embodiment 10 is the photocatalyst of embodiment 9, wherein the metal is gold or palladium or a combination thereof. Embodiment 11 is the photocatalyst of embodiment 10, wherein the palladium is deposited on the photoactive material and on the gold. Embodiment 12 is the photocatalyst of any one of embodiments 1 to 11, wherein the photocatalyst is in particulate or powdered form. Embodiment 13 is the photocatalyst of any one of embodiments 1 to 12, wherein the electrically conductive material is a plurality of nanostructures such as nanoparticles. Embodiment 14 is the photocatalyst of embodiment 13, wherein the average particle size of the nanoparticles is from 1 to 10 nanometers. Embodiment 15 is the photocatalyst of any of embodiments 1 to 14, comprising 0.001 to 5 wt. % of the electrically conductive material. Embodiment 16 is the photocatalyst of any of embodiments 1 to 15, wherein the electrically conductive material covers between 0.001% to 5% of the total surface area of the photoactive material. Embodiment 17 is the photocatalyst of any of embodiments 1 to 16, wherein the photocatalyst is comprised in a composition that includes water. Embodiment 18 is the photocatalyst of embodiment 17, wherein the composition further comprises a sacrificial agent. Embodiment 19 is the photocatalyst of embodiment 18, wherein the sacrificial agent is methanol, ethanol, propanol, iso-propanol, n-butanol, iso-butanol, ethylene glycol, propylene glycol, glycerol, or oxalic acid, or any combination thereof. Embodiment 20 is the photocatalyst of embodiment 19, wherein the sacrificial agent is ethanol or ethylene glycol. Embodiment 21 is the photocatalyst of any one of embodiments 17 to 20, wherein the composition comprises 0.1 to 5 g/L of the photocatalyst and/or 0.1 to 5 vol. % of the sacrificial agent. Embodiment 22 is the photocatalyst of any one of embodiments 1 to 21, wherein the photocatalyst is self-supported. Embodiment 23 is the photocatalyst of any one of embodiments 1 to 21, wherein the photocatalyst is supported by a substrate such as glass, polymer beads, or metal oxides. Embodiment 24 is the photocatalyst of any one of embodiments 1 to 23, wherein the photocatalyst is capable of catalyzing the photocatalytic electrolysis of water. Embodiment 25 is the photocatalyst of embodiment 24, wherein the H 2 production rate from water is 1×10 −3 to 1×10 −7 mol/g Catal min. Embodiment 26 is a system for producing hydrogen gas and oxygen gas from water, the system comprising: (a) a transparent container comprising a composition that includes the photocatalyst of any one of embodiments 1 to 25, water, and a sacrificial agent; and (b) a light source for irradiating the composition. Embodiment 27 is the system of embodiment 26, wherein the light source is sunlight. Embodiment 28 is the system of embodiment 26, wherein the light source is an ultra-violet lamp. Embodiment 29 is the system of any one of embodiments 26 to 28, wherein an external bias is not used to produce the hydrogen gas and oxygen gas. Embodiment 30 is a method for producing hydrogen gas and oxygen gas from water, the method comprising obtaining a system of any one of embodiments 26 to 29 and subjecting the composition to the light source for a sufficient period of time to produce hydrogen gas and oxygen gas from the water. Embodiment 31 is the method of embodiment 30, wherein an external bias is not used to produce the hydrogen gas and oxygen gas. Embodiment 32 is the method of any one of embodiments 30 to 31, wherein the H 2 production rate from water is 1×10 −3 to 1×10 −7 mol/g Catal min. Embodiment 33 is the method of any one of embodiments 30 to 32, wherein the light source has a flux between about 0.1 mW/cm 2 and 30 mW/cm 2 . Embodiment 34 is a method of preparing any one of the photocatalysts of embodiments 1 to 25 comprising obtaining the photoactive material and depositing the electrically conductive material on the photoactive material. Embodiment 35 is the method of embodiment 34, further comprising tuning the photoactive material such that the photonic band gap of said at least partially overlaps with the electronic band gap of said material. Embodiment 36 is the method of embodiment 35, wherein the structure of the photoactive material is an inverse opal. Embodiment 37 is the method of embodiment 36, wherein the photonic band gap of said material is tuned by modifying the diameter of the pore size of the inverse opal structure such that an increase in said pore size results in an increase in the photonic band gap of said material.
The following includes definitions of various terms and phrases used throughout this specification.
“Water splitting” or any variation of this phrase describes the chemical reaction in which water is separated into oxygen and hydrogen.
“Inhibiting,” “preventing,” or “reducing” or any variation of these terms, when used in the claims or the specification includes any measurable decrease or complete inhibition to achieve a desired result. By way of example, reducing the spontaneous emission of an excited electron encompasses a situation where a decrease in the amount of spontaneous emission occurs in the presence of a photocatalyst or photoactive material of the present invention when compared with a situation where, for example, a photoactive material is used that does not have its photonic band gap tuned with or at least partially overlapping with the material's electronic band gap.
“Effective” or any variation of this term, when used in the claims or specification, means adequate to accomplish a desired, expected, or intended result.
“Nanostructure” refers to an object or material in which at least one dimension of the object or material is equal to or less than 100 nm (e.g., one dimension is 1 to 100 nm in size). In a particular aspect, the nanostructure includes at least two dimensions that are equal to or less than 100 nm (e.g., a first dimension is 1 to 100 nm in size and a second dimension is 1 to 100 nm in size). In another aspect, the nanostructure includes three dimensions that are equal to or less than 100 nm (e.g., a first dimension is 1 to 100 nm in size, a second dimension is 1 to 100 nm in size, and a third dimension is 1 to 100 nm in size). The shape of the nanostructure can be of a wire, a particle, a sphere, a rod, a tetrapod, a hyperbranched structure, or mixtures thereof.
The term “about” or “approximately” are defined as being close to as understood by one of ordinary skill in the art, and in one non-limiting embodiment the terms are defined to be within 10%, preferably within 5%, more preferably within 1%, and most preferably within 0.5%.
The use of the word “a” or “an” when used in conjunction with the term “comprising” in the claims or the specification may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.”
The words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.
The photoactive catalysts and photoactive materials of the present invention can “comprise,” “consist essentially of,” or “consist of” particular components, compositions, ingredients etc. disclosed throughout the specification. With respect to the transitional phase “consisting essentially of,” in one non-limiting aspect, a basic and novel characteristic of the photoactive catalysts and materials of the present invention are their ability to efficiently use excited electrons in water-splitting applications to produce hydrogen.
Other objects, features and advantages of the present invention will become apparent from the following figures, detailed description, and examples. It should be understood, however, that the figures, detailed description, and examples, while indicating specific embodiments of the invention, are given by way of illustration only and are not meant to be limiting. Additionally, it is contemplated that changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 : Schematic diagram of a water splitting system of the present invention.
FIG. 2 : (A) TEM of PBG Au/TiO 2 photocatalyst. (B) Particle size distribution of Au and TiO 2 particles in the PBG Au/TiO 2 photocatalyst. (C) XPS Au4f for two PBG Au/TiO 2 photo-catalysts (the atomic % of Au was 0.55 and 0.51 for PBG-585 nm (i) and PBG-357 nm (ii) respectively). (D) and (E) High Resolution TEM of 2 and 4 wt. % Au of the PBG Au/TiO 2 catalysts indicating the uniform distribution of Au particles at both loads of Au.
FIG. 3 : UV-Vis reflectance spectra for a TiO 2 inverse opal with macropore diameter (D)=200 nm in air (n=1.00) and in water (n=1.34). The spectra were collected along the [111] direction of a TiO 2 inverse opal thin film. The PBG for Bragg diffraction on f.c.c. (111) planes is observed at 357 nm in air, and 450 nm in water. The shift in the PBG on immersion of the inverse opal in water results from an increase in the average refractive index of the photonic crystal when it is filled with water. The attenuation of the reflectance peak in water is due to increased scattering of light and a decrease in refractive index contrast between titania (n=2.1-2.3 for sol-gel derived anatase) and the medium filling the macropores.
FIG. 4 : UV-Vis reflectance spectra for a TiO 2 inverse opal with macropore diameter (D)=320 nm in air (n=1.00) and in water (n=1.34). The spectra were collected along the [111] direction of a TiO 2 inverse opal thin film. The PBG for Bragg diffraction on f.c.c. (111) planes is observed at 585 nm in air, and 721 nm in water. The shift in the PBG on immersion of the inverse opal in water results from an increase in the average refractive index of the photonic crystal when it is filled with water.
FIG. 5 (A)-(C): (A) Hydrogen production from water using photocatalysts with two different PBG positions under UV light with flux of about 1-1.2 mW/cm 2 and under direct sunlight with UV flux of about 0.3-0.4 mW/cm 2 . The Au/TiO 2 with the PBG position close to its electronic band gap is 2 to 3 times more active than an exactly similar material in all respects (except macroporosity and PBG properties) and where the PBG is far from the electronic band gap. Under direct sunlight PBG materials are active despite the lower UV flux. The highest performance was found for the Au—Pd/TiO 2 PBG 360 nm. (B) SEM images of the two PBG Au/TiO 2 photocatalysts. Hydrogen production rates are given in (C).
FIG. 6 : SEM images of PBG 585 nm inverse opal TiO 2 at the indicated magnification.
FIG. 7 : Dark Field Transmission Electron Microscopy of 0.5 wt. % of Au-0.5 wt. % Pd/TiO 2 . The bright dots are those of Au and Pd metals. Inset: EDS analysis indicating the presence of both Au and Pd.
FIG. 8 : UV-Vis absorbance spectra for TiO 2 inverse opal powders with macropore diameters of 200 nm and 320 nm in air. The spectra show strong absorption below 400 nm due to anatase TiO 2 . PBGs are not seen in the spectra because the lattice planes are randomly oriented and the PBGs are broad due to the high refractive index of TiO 2 . Deposition of gold nanoparticles on the TiO 2 supports gives rise to intends absorption bands at ˜580 nm due to the gold surface plasmon resonance, which contributes to the high photocatalytic activity of these samples under direct sunlight.
FIG. 9 Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images of TiO 2 photonic band gap (PBG) materials heated to different temperatures.
FIG. 10 XRD of the PBG TiO 2 materials annealed at different temperature.
FIG. 11 UV-Vis transmittance solvent studies PBG TiO 2 materials.
FIG. 12 Hydrogen production yield of the PBG materials annealed at the indicated temperatures (with ethanol to water volumetric ratio of 80:20).
FIG. 13 Hydrogen production yield of the PBG materials annealed at the indicated temperatures (with ethanol to water volumetric ratio of 2:98).
DETAILED DESCRIPTION OF THE INVENTION
While hydrogen-based energy has been proposed by many as a solution to the current problems associated with carbon-based energy (e.g., limited amounts and fossil fuel emissions), the currently available technologies are either expensive, inefficient, or unstable. The present application provides a solution to these issues. The solution is predicated on the use of conductive material and a photoactive material that has a photonic band gap (e.g., structures such as inverse opals and photonic crystals) and an electronic band gap (e.g., semi-conductive materials) that are tuned with or overlap with one another, the result of which allows for efficient hydrogen production by splitting water via a light source such as sunlight or a UV lamp. In particular aspects, it was further discovered that a combination of gold and palladium as the conductive material resulted in a more efficient catalyst when compared with a system in which gold alone was used as the conductive material.
These and other non-limiting aspects of the present invention are discussed in further detail in the following sections.
A. Photoactive Catalysts
The photoactive catalysts of the present invention include a photoactive material and a conductive material deposited on at least a portion of the surface of the photoactive material.
With respect to the photoactive material, such material includes a photonic band gap (e.g., inverse opal structures, photonic crystals, etc.) and an electronic band gap (e.g., semi conductive materials). Materials have a photonic band gap are materials that can control the propagation of electromagnetic radiation by creating periodic dielectric structures. A photonic band gap material can prohibit the propagation of electromagnetic radiation within a specified frequency range (band) in certain directions. Stated another way, such materials can prevent light from propagating in certain directions with specified energies. This can be thought of as the complete reflection of electromagnetic radiation of a particular frequency directed at the material in at least one direction because of the particular structural arrangement of separate domains of the material, and refractive indices of those domains. The structural arrangement and refractive indices of the separate domains that make up such materials form photonic band gaps that inhibit the propagation of light centered around a particular frequency. There are one-, two-, and three-dimensional photonic band gap materials. One-dimension materials have structural and refractive periodicity in one direction. Two-dimensional materials have periodicity in two directions. Three-dimensional materials include periodicity in three directions.
In particular aspects of the present invention, three-dimensional photonic materials are used. One non-limiting aspect of preparing a three-dimensional photonic band gap material includes infiltration of a fluid, which may be a liquid or a gas, into a template solid having substantially continuous porosity throughout its extent. This is followed by solidifying the fluid and then removing the template solid. The resulting structure is formed such that its solid portion is substantially in the positions of the continuous porosity of the template solid and its pores are substantially in the positions of the solid members of the template solid. In more particular embodiments, the colloidal crystal template technique can be used, which includes the following general steps:
(a) Generally the utilization of colloidal crystal templating for the fabrication of inverse opal photonic crystals involves three main steps. Firstly the 3 dimensional synthetic opal is fabricated by the self-assembly of monodisperse colloidal polymer spheres (e.g., Monodisperse poly(methylmetacrylate) (PMMA) colloids) into an face centered cube (FCC) lattice. Along the FCC [111] plane a PBG should open in the opaline structure resulting in the reflection of a range of wavelengths (depending on the diameter of the sphere) across the electromagnetic spectrum. Second, a sol-gel of a dielectric material infiltrates the pore spacing in the colloidal crystal template. Subsequent hydrolysis and condensation reactions lead to the formation of a network solid. The solid semi-conductive material (e.g., TiO 2 ) formed can then be hydrated to an amorphous form and will have a higher overall refractive index than that of single crystals. Hence the material must be dried in air, after which time calcination is used to remove the colloidal crystal template. This leaves behind an inverse opal structure with a periodically modulated refractive index in 3-D; a macroporous FCC array of air spheres in a dielectric matrix. (b) Two methods can be used to deposit conductive material on the surface of the colloid. The routes are differentiated at what stage the conductive material (e.g., gold) is added. In route 1, the conductive material solution (e.g., containing the desired % of metal ions (e.g., Au ions) from their precursor material (e.g., HAuCl 4 .3H 2 O is prepared in advance, and added into the semi-conductive material (e.g., TiO 2 ) after formation of inverse opal structure (after the templates were removed). In route 2 the solid HAuCl 4 .3H 2 O were weighted and added to the semi-conductive precursor solution before infiltration of the templates.
Calcination at 450° C. can be used to remove the PMMA template as well as to crystalize the semi-conductive material (e.g., TiO 2 ) and disperse the conductive material (e.g., gold nanoparticles) throughout the inverse opal structure. As shown in the data, calcination at 500° C. to 800° C. is preferable when TiO 2 is used, and more preferably 550° C. to 750° C., and most preferably between 600° C. to 700° C. In both routes, after the conductive material is added, the samples change color from slightly yellow to a distinct purple in the case of Au—TiO 2 . This color change is due to the reduction of Au(III) to Au(0) and the purple color of gold nanoparticles is the result of surface plasmon resonance of gold, which can be affected by various parameters such as size of the particle, shape and the refractive index of media. Route 1 gave more evenly distributed color compared to the route 2, which means higher dispersion of gold on the surface of titania, and likely smaller Au particle size is achievable with route 1 which is beneficial for enhancement of photoactivity.
A material's electronic band gap can be extracted from its UV-Vis absorption spectra such as the given in FIG. 8 by extending the tangent of the curve to the x-axis (energy or wavelengths). For instance, and with reference to FIG. 8 , it is seen that TiO 2 absorbs light with wavelength less than 400 nm, extrapolation of the tangent to the curve on the x-axis gives the wavelength (or energy) position at the edge of the band gap (approximately 390 nm or close to 3.1 eV).
A material's photonic band gap can be calculated by measuring the distance between two repeating microscopic unit cells (D) using the following formula:
mλ= 2 d hkl √{square root over ( n avg 2 −sin 2 θ ext )} (equation 1),
where m is the diffraction order, θ is the incident angle of light with respect to the surface normal, d hkl is
d hkl = 2 D ( h 2 + k 2 + l 2 ) ( equation 2 )
where D is the macropore diameter and h, k, l are miller indices of the exposed planes, and n avg is the average refractive index of the photonic crystal (n avg =[φ solid n solid +(1−φ solid )n void ]). The average refractive index of the three-dimensional structure (e.g., photonic crystal or inverse opal), and hence the PBG position, λ, depend on the refractive index of the medium filling the macropores in the structure.
By using these parameters, one can then tune the photonic band gap of a given material to be identical with, substantially identical with, or at least partially overlap with said material's electronic band gap. The photonic band gap of the material can be modified as needed by using the above equations. In particular, combining equations 1 and 2 one gets:
m λ = 2 D ( h 2 + k 2 + l 2 ) n avg 2 - sin 2 θ ext . ( equation 3 )
For a first order diffraction m=1 and FCC close packed structure (111) and incident light perpendicular to the [111] plane (θ=0) equation 3 is simplified to:
λ = 2 2 3 D n avg . ( equation 4 )
In other words, increasing the macropore size (D) of the opal materials directly increases the photonic band gap (A).
B. Uses of the Photocatalysts
Once the photocatalysts of the present invention are prepared and properly tuned, they can be used in water-splitting systems. FIG. 1 provides a non-limiting illustration of how such a system 10 could be used to split water to produce H 2 and O 2 . A light source 11 (e.g., natural sunlight or UV lamp) contacts the photocatalytic material 12 , thereby exciting electrons 13 from their valence band 14 to their conductive band 15 , thereby leaving a corresponding hole 16 . The electrons 13 are used to reduce hydrogen ions to form hydrogen gas, and the holes are used to oxidize oxygen ions to oxygen gas. The hydrogen gas and the oxygen gas can then be collected and used in down-stream processes. As explained elsewhere, due to the photonic band gap being tuned with or at least partially overlapping with the electronic band gap of the photocatalytic material 12 , the electrons 13 can remain in the conductive band for a longer period of time when compared with a system in which the photonic band gap is not tuned with or does not at least partially overlap with the electronic band gap of said material 12 .
EXAMPLES
The present invention will be described in greater detail by way of specific examples. The following examples are offered for illustrative purposes only, and are not intended to limit the invention in any manner. Those of skill in the art will readily recognize a variety of noncritical parameters which can be changed or modified to yield essentially the same results.
Example 1
Materials and Methods Used to Prepare, Test, and Characterize Photocatalysts
TiO 2 inverse opal powders with macro pore diameters (D) of 200 nm or 320 nm, and photonic band gaps along the [111] direction in air of 357 nm and 585 nm, respectively, were fabricated by the colloidal crystal template technique. Colloidal crystals composed of mono-disperse PMMA colloids (diameters 235 nm or 372 nm, respectively) were prepared using a flow-controlled vertical deposition method (Zhou, et al., 2005; Zhou, et al., 2004) to deposit a PMMA colloidal crystal film on a planar substrate and then infiltrated with a TiO 2 sol-gel precursor. Careful drying and calcination of the resulting TiO 2 /PMMA (polymethylmethacrylate) composites selectively removed the PMMA template, yielding 3-dimensionally ordered macroporous TiO 2 inverse opals supports. Gold nanoparticles were subsequently deposited on the TiO 2 inverse opals supports using the deposition with urea method (Cushing, et al., 2012). The obtained photocatalysts, labeled Au/TiO 2 (PBG-357 nm) and Au/TiO 2 (PBG-585 nm), respectively, were then subjected to structural, chemical and photocatalytic characterization as outlined in the following Examples.
Photocatalytic tests were conducted under batch conditions. Typically 10-25 mg of catalyst was loaded into a 200 mL Pyrex reactor. Catalysts were reduced with H 2 for one hour at 300° C. prior to reaction; this was followed by purging with N 2 under continuous stirring until all hydrogen was removed. Water (60 mL) was added to the reactor and variable amounts of ethanol (from 0.1 mL to 5 mL). A ultra-violet (UV) lamp (Spectra-line-100 W) was used with a cut off filter of 360 nm and above. The UV flux at the front side of the reactor was between about 1-1.2 mW/cm 2 . Sampling was conducted approximately every 30 minutes. For reactions conducted under sunlight, the same reactor was put under the sun and the UV flux was monitored (the values oscillated between 0.25 and 0.40 mW/cm 2 from 10 to 4 pm); catalyst were not stirred under direct sunlight excitation. Products were analyzed using GCs equipped with thermal conductivity detector TCD and Porapak packed column at 45° C. and with N 2 as the carrier gas. For O 2 detection a GC equipped with TCD was also used but with He as carrier gas.
Transmission electron microscopy studies were performed at 200 kV with a JEOL JEM 2010F instrument equipped with a field emission source. For each sample, more than 300 individual TiO 2 and Au nanoparticles were used for particle size determinations. Samples were dispersed in alcohol in an ultrasonic bath and a drop of supernatant suspension was poured onto a carbon coated copper TEM grid for analysis.
SEM images were taken using a Philips XL-30 field emission gun scanning electronmicroscope (FEGSEM). All micrographs were collected at an electron gun accelerating voltage of 5 kV. Specimens were mounted on black carbon tape and platinum sputter coated for analysis.
The XPS data were collected on a Kratos Axis UltraDLD equipped with a hemi-spherical electron energy analyzer. Spectra were excited using monochromatic Al Kα X-rays (1486.7 eV) with the X-ray source operating at 100 W. Survey scans were collected with a 160 eV pass energy, whilst core level Au4f scans were collected with a pass energy of 20 eV. The analysis chamber was at pressures in the 10 −10 torr range throughout the data collection.
Photoluminescence was collected on a Perkin-Elmer LS-55 Luminescence Spectrometer. The excitation wavelength was set at 310 nm and spectra were recorded over a range of 330-600 nm using a standard photomultiplier. A 290 nm cut off filter was used during measurements.
UV-Visabsorbance spectra were taken over the range 250-900 nm on a Shimadzu UV-2101 PC spectrophotometer equipped with a diffuse reflectance attachment for powder samples.
UV-Visible reflectance spectra of the TiO 2 inverse opal thin films in air and water were collected using an Ocean Optics CCD S-2000 spectrometer fitted with a microscope objective lens coupled to a bifurcated fiber optic cable. A tungsten light source was focused on to the polypyrrole (PPy) films with a spot size of approximately 1-2 mm 2 . Reflectivity data were recorded with a charge-coupled device CCD detector in the wavelength range of 300-900 nm. Sample illumination and reflected light detection were performed along the surface normal.
Example 2
Data
FIG. 2 presents transmission electron microscopy (TEM), high resolution TEM (HRTEM) and X-ray photo electron spectroscopy (XPS) of two PBG catalysts (PBG-357 nm and PBG-585 nm). The properties and composition of Au/TiO 2 catalysts, where the TiO 2 is present in the anatase form, are given. The 3-dimensionally ordered macroporous structure of the PBG materials is clearly seen in FIG. 2A , and the anatase TiO 2 crystallites (analyzed by X-ray diffraction (XRD)—not shown) and Au nanoparticles are seen in FIGS. 2D and E. The particle size distribution of both TiO 2 and Au are presented in FIG. 2B ; both components (Au and TiO 2 ) are of comparable size with the Au particles smaller. Au4f XPS indicates that Au is present in its metallic form with no apparent charge donation from/to the semiconductor to the metal. The Au/TiO 2 (PBG-357 nm) and Au/TiO 2 (PBG-585 nm) catalysts prepared in this study are near identical in their chemical compositions as well as their main characteristics (particle sizes, Brunauer-Emmett-Teller (BET) surface area, 60 m 2 /g, exposed area of Au, support phase and valence band electronic structure 14 ) but differ in their macropore diameter and optical PBG properties. One has a PBG along the [111] direction of 357 nm (in air) whilst the other has its PBG along the [111] direction of 585 nm (in air), as determined from UV-Vis reflectance measurements on TiO 2 inverse opal thin films ( FIG. 3 and FIG. 4 ). The PBG can be calculated from the distance between two repeating microscopic unit cells (D) using the following formula:
mλ= 2 d hkl √{square root over ( n avg 2 −sin 2 θ ext )},
where m is the diffraction order, θ is the incident angle of light with respect to the surface normal, d hkl is
m λ = 2 D ( h 2 + k 2 + l 2 )
where D is the macropore diameter and h, k, l are miller indices of the exposed planes, and n avg is the average refractive index of the photonic crystal (n avg =[φ solid n solid +(1−φ solid )n void ]). The average refractive index of the photonic crystal, and hence the PBG position, λ, depend on the refractive index of the medium filling the macropores in the TiO 2 inverse opal.
FIG. 5 shows scanning electron microscopy (SEM) images for the Au/TiO 2 (PBG-357 nm) and Au/TiO 2 (PBG-585 nm) samples ( FIG. 6 presents larger SEM images of TiO 2 at PBG-585 nm), and photo reaction data for water splitting to hydrogen in the presence of 0.5 vol. % of ethanol. Ethanol is used in this case as a sacrificial hole scavenger to reduce electron-hole recombination rate. It was discovered that ethylene glycol, methanol and oxalic acid could also be used successfully as sacrificial agents at concentrations as low as 0.1 vol. %. Ethanol is preferred because of its bio-renewable origin, although glycols are also attractive for this purpose as they are common industrial waste products that are often incinerated. Economic analyses indicate that the cost of sacrificial agent (at such a low %) is a fraction of the cost of the whole process. Both catalysts prepared in this study were highly active for the water splitting reaction. However, the Au/TiO 2 (PBG-357 nm) photocatalyst was about three times more active than the Au/TiO 2 (PBG-585 nm) photocatalyst. For comparison under similar conditions, 2 wt. % Au/TiO 2 (anatase) or 4 wt. % Au/TiO 2 (anatase) photo catalysts with similar particle size distributions, but not based on inverse opal TiO 2 supports (Murdoch, et al., 2011), gave only around one fifth of the activity of the Au/TiO 2 (PBG-357 nm) photocatalyst. It is believed that the difference in activity is due to the overlap between the PBG of the TiO 2 inverse opal support and the electronic band gap of anatase TiO 2 (about 380 nm). It is particularly surprising that under direct sunlight the PBG catalysts perform even better than under direct UV, even though the UV flux from the sunlight is weaker. It is worth noting that the TiO 2 inverse opal (alone) had negligible photo catalytic activity for H 2 production under UV or sunlight. The presence of a metal (or other co-catalysts) fast electron transfer and accumulation from the conductive band (CB) occurs thus further providing available sites for hydrogen ions reduction. Assays further confirmed that the amount of Au can be decreased from 2 wt. % to 0.5 wt. % when combined with 0.5 wt. % of Pd, both deposited on PBG-357 nm catalyst (see FIG. 7 ). The reaction rate was found to be about 0.6×10 −3 mol/g Catal h ( FIG. 5 ) higher than that observed over the 2 wt. % Au/TiO 2 PBG-357 nm.
Data in FIG. 4 demonstrate that the photocatalytic properties of TiO 2 inverse opal based photocatalysts are strongly enhanced when the PBG and electronic absorption of TiO 2 are coupled. The equations above indicate that the PBG (λ) for a TiO 2 inverse opal is dependent on the macropore diameter (D), the Miller index of the plane from which light is being diffracted (hkl), the incident light angle and the average refractive index of the material (n avg ). The latter will vary with TiO 2 solid volume fraction and the medium filling the macropores. Higher index planes will have photonic band gaps at shorter wavelengths, whilst filling the macropores with water (the reactant and main H 2 source in this case) will increase the average refractive index of the inverse opal and red shift the PBG ( FIGS. 2 and 3 ). The high hydrogen production rates observed for the photocatalysts prepared in this study, and in particular the Au/TiO 2 (PBG-357 nm) sample in sunlight, can be attributed to the fact that light from the sun changes its incident angle during the day. This allows PBGs from different planes in the TiO 2 inverse opal structure to overlap with the electronic absorption band of TiO 2 (and hence suppress spontaneous emission and electron-hole pair recombination in TiO 2 ). Another possible contributing factor is the presence of the plasmon resonance of Au particles absorbing in the visible region ( FIG. 8 ).
A detailed analysis of the reaction products was conducted to understand the mechanisms of H 2 production in the current study. Traces of acetaldehyde, methane and ethylene are seen (Table 1). Next to hydrogen in production is CO 2 (CO was not detected).
TABLE 1 (Reaction rates under direct sunlight excitation (UV flux = 0.25-0.35 mW/ cm 2 ) over 2 wt. % Au/TiO 2 (PBG-357 nm) photocatalyst in presence of 0.5 vol. % of ethanol) Product Reaction rate in mol/(g Catal min) Hydrogen 1.5-2 × 10 −5 CO 2 0.1-0.3 × 10 −5 C 2 H 4 Ca. 1 × 10 −7 CH 3 CHO Traces (0.7 × 10 −8 ) CH 4 Traces (0.4 × 10 −8 )
It is believed that the hydrogen production rate seen in Table 1 is the highest reported rate in photocatalytic systems using such a small amount of a sacrificial agent and direct sunlight. Notably, from the H 2 production rate and the amount of UV photons hitting the reactor it was calculated that about 80% of the UV photons were converted. In particular, FIG. 5 shows hydrogen production at about 500 minutes is ca. 5×10 −4 mol/g of catalyst at a UV flux close to 0.5 mW/cm 2 (as upper limit). The flux converted to number of photons using Plank's equation (at a wavelength average of 360 nm)=5.5×10 14 photons per second hitting the area of the catalyst inside the reactor, at the maximum (catalyst amount 25 mg in 200 mL reactor). The amount of hydrogen produced per second is about 2.5×10 14 molecules. Since each hydrogen molecule needs two electrons to form two photons are involved. Therefore the total number of photons consumed is 5×10 14 . Dividing the number of photons consumed by the number of photons hitting the catalyst gives about full conversion of the UV light.
Further tests were conducted to determine the stability of the Au/TiO 2 (PBG-357 nm over long periods of time. In particular, this photocatalyst showed consistent hydrogen production rates for periods of time up to 10,000 minutes, indicating that it may indeed prove suitable for large scale H 2 production.
Based on this study and previously studied reactions the following steps describe the chemical processes involved.
Step 1 . Dissociative adsorption of ethanol and water occurs on the surface of TiO 2 in the presence or absence of light (Nadeem, et al., 2010; Jayaweera, et al., 2007):
CH 3 CH 2 OH+Ti 4+ —O s 2− →CH 3 CH 2 O—Ti 4+ +OH( a )
H 2 O+Ti 4+ —O s 2− →HO—Ti 4+ +OH( a ).
S for surface, (a) for adsorbed.
Step 2 . Light excitation resulting in electron (e − )-hole (h + ) pair formation:
TiO 2 +UV→ e − +h +
Plasmonic Au injection into the conductive band (CB) of TiO 2 (up to 10 3 electrons per 10 nm Au particle (30,000 atom) (Du, et al., 2009).
Step 3 . Hole scavenging (two electrons injected per ethoxide into the valence band (VB) of TiO 2 ) followed by acetaldehyde formation (Miller, et al., 1997):
CH 3 CH 2 O—Ti s 4+ —O 2− s +2 h + →CH 3 CHO( g )+OH( a )+Ti s 4+ .
Step 4 . Electron transfer from the CB of TiO 2 to hydrogen ions (via Au nanoparticles) resulting in molecular hydrogen formation and hole transfer from one OH species (see equation b in step 1 ) of water:
4OH( a )+4 e − +2 h + →3O s 2− +½O 2 +2H 2 .
Step 5 . Acetaldehyde decomposition; a slightly exothermic reaction:
CH 3 CHO( g )→COCH 4 .
Step 6 . Water gas shift reaction; a mildly exothermic reaction (ΔH=−41 kJmol −1 ):
CO+H 2 O→CO 2 +H 2 .
Competing with step 5 is the coupling of two CH 3 radicals to C 2 H 6 that is farther dehydrogenated to C 2 H 4 . The Photo-Kolbe process of CH 3 COOH has been studied in some details over TiO 2 single crystals (Wilson & Idriss, 2003; Wilson & Idriss, 2002) and powder (Muggli & Falconer, 1999). In the process the coupling of two CH 3 radicals to C 2 H 6 competes with the coupling of CH 3 with H radicals to CH 4 .
Considering the above steps, the ratio of H 2 to CO 2 should be 2 (if water is not involved) and 3 (if one water molecule is involved, step 1 b ); however the H 2 to CO 2 ratio observed in all runs of this study varied between 6 and 10 depending on the reaction conditions. This indicates that large amounts of hydrogen are produced directly from water rather than simply considering the two electron injections of step 3 . Hole trapping (electron injections) by ethanol occurs very fast (a fraction of a nanosecond [Sabio, et al., 2010]) while the charge carrier disappearance rate is slower (multiples of nanoseconds) in anatase TiO 2 . The plasmonic effect of Au atoms have been observed (Linic, et al., 2011) to considerably affect electron transfer where up to 10 3 electrons are injected into the CB of TiO 2 per Au particle of about 10 nm. Also it has been reported that due to the enhancement of the electric field caused by the plasmonic excitation the rate of h + and e − generation is increased few orders of magnitudes at the interface Au—TiO 2 . In other words the photo excited Au particles behave like nanosized concentrators amplifying the intensity of local photons (Linic, et al., 2011).
In summary, Au/TiO2 photocatalysts, based on inverse opal TiO2 supports, exhibit remarkable photocatalytic activity and stability for photocatalytic water splitting under UV and sunlight. Coincidence of the optical (PBG position) and electronic (TiO 2 absorption edge) properties of the TiO 2 inverse opal support suppresses electron-hole pair recombination in TiO 2 , and thus enhances the photocatalytic activity of Au/TiO 2 photocatalysts for H 2 production from water. Supported gold nanoparticles act as sites for H 2 production and may allow visible light excitation of Au/TiO 2 photocatalysts via the gold surface plasmon. The Au/TiO 2 and Au—Pd/TiO 2 (PBG-357 nm) photocatalyst described in this work demonstrated a H 2 production rate of about 1 mol H 2 /k gcat . h from water (with very small amounts of sacrificial agent: ethanol 0.5 vol. %) under sunlight, and excellent operational stability.
Example 3
Anatase/Rutile Ratio and Photocatalytic Performance
A series of three-dimensional ordered macroporous (3DOM) TiO 2 (pure anatase) was prepared in order to study its photo-catalytic activity in the context of the present invention. These materials were prepared in the manner outlined above with respect to Example 1 and were confirmed to have overlapping electronic band and photonic band gaps. All prepared catalysts had a fixed loading of 0.50 wt. % Pd and 1.00 wt. % Au. The materials were initially made of TiO 2 anatase of particle size of about 10 nm.
The objective was to test the activity of these materials as prepared as well as that after heating to high temperature (prior to the bimetal deposition). The objective of heating these materials was to transform part of the anatase phase to the rutile phase and exploit their potential synergistic effect on the reaction. See Synergism and photocatalytic water splitting to hydrogen over Pt/TiO 2 catalysts: Effect particle size. Bashir, S. Wahab, A. K., Idriss, H. Catalysis Today. DOI: 10.1016/j.cattod.2014.05.034; Photoreaction of Au/TiO 2 for hydrogen production from renewables: a review on the synergistic effect between anatase and rutile phases of TiO 2 . K. Connelly, A. K. Wahab, Hicham Idriss, Materials for Renewable and Sustainable Energy, 1:3, 1-12 (2012)).
FIG. 9 provides data showing the 3DOM TiO 2 materials heated at different temperatures (500° C.; 800° C.; and 900° C.) for 2 hours in each case and then studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). It can be seen that heat treatments resulted in increasing the cell walls (materials) and consequently decreasing the pore size. The treatment therefore resulted in blue shift of the PBG of the materials. As per the above equation relating the pore size (D) to the wavelength (λ), the decrease is the pore size (D) would decrease lambda (the photonic band gap).
FIG. 10 provides x-ray diffraction data of the 3DOM TiO 2 materials annealed at different temperatures. The 500° C. is composed of pure anatase phase (see the 2θ at 25.2° attributed to the (101) line of anatase and the “quasi” absence of the (110) line of the rutile at 2θ=27.4°). Upon annealing, the signal related to anatase phase decreases and that related to rutile increases with increasing temperature. Table 2 is data extracted from FIG. 10 where the % of anatase and rutile is calculated as well as the corresponding crystallite size. It is noted that the crystallite size of both phases increased with increasing temperature. This is thought be the reason behind the increase in wall thickness and the corresponding decrease in the ordered pore size which results in changing the materials.
TABLE 2
Average anatase
Average rutile
wt. %
wt. %
crystallite size, L
crystallite size, L
Sample
Anatase
Rutile
(nm)
(nm)
3DOM TiO 2 at
91.1
8.9
18.2
8.0
500° C.
3DOM TiO 2 at
90.2
9.8
31.9
14.4
600° C.
3DOM TiO 2 at
88.5
11.5
38.7
22.1
650° C.
3DOM TiO 2 at
82.8
17.2
53.0
28.9
700° C.
3DOM TiO 2 at
80.7
19.3
163.0
58.3
800° C.
3DOM TiO 2 at
1.8
98.2
—
87.0
900° C.
FIG. 11 provides an example of the UV-Vis transmittance solvent studies data carried out to determine macropore sizes and solid content of 3DOM samples. Taking a regression of PBG positions vs. n solvent , slopes and intercepts were obtained from which the dimension of the pores were extracted and compared with those calculated from SEM and TEM measurements. Table 3 provides a summary of these data. The use of different solvents changes the refractive indices of the media so the photonic band gap can be computed. The data provided are given as an example only. It is clear however that one can make the PBG coincide not only with the electronic band gap but also with the plasmonic resonance of the metal (Au) in this case (in the range 500-650 nm depending on the particle size and shape; see foe example S. Link and M. A. El-Sayed, Int. Reviews in Physical Chemistry, 2000, Vol. 19, No. 3, 409-453.)
TABLE 3
D SEM
D solvent
Sample
(nm)
D TEM (nm)
(nm)
Exp. φ titania (%)
3DOM TiO 2 (500° C.)
354
360
345
13
3DOM TiO 2 (800° C.)
342
340
344
14
3DOM TiO 2 (900° C.)
311
279
297
22
FIGS. 12 and 13 present the hydrogen production yield of the materials annealed at the indicated temperatures but with different % of ethanol as a sacrificial agent. In FIG. 12 ethanol:water volumetric ratio is equal to 80:20, while that in FIG. 13 the ethanol:water ratio was 02:98. The dependence of the hydrogen production on the amount of sacrificial agent can change with the nature of the catalyst used, yet in general there are two maxima one organic rich and one water rich. The production and therefore the rate increased upon annealing from 600° C. to 700° C. (17% of rutile phase) then decreased again. The sample annealed at 900° C. (mainly rutile) showed negligible activity. The increase in activity was linked to the presence of both phases, anatase and rutile, with a range of about 82.8 wt. % to 90.2 wt. % anatase and 17.2 wt. % to 9.8 wt. % rutile having the highest hydrogen production rate.
REFERENCES
The following references to the extent that they provide exemplary procedural or other details supplementary to those set forth herein, are specifically incorporated by reference.
“Technoeconomic Analysis of Photoelectrochemical (PEC) Hydrogen Production, Direct Technologies under the Department of Energy (DOE) contract number: GS 10E-009J, 2009. Chen, et al., Science. 331:746-750, 2011. Chueh, et al. Science. 330:1797-1801, 2010. Cushing, et. al., J Am Chem Soc. 134:15033-15041, 2012. Du, J Phys Chem. 113:6454-6462, 2009. Frame, et al., J Am Chem Soc. 133(19):7264-7, 2011. Fujishima & Honda, Nature. 238:37-38, 1972. Hanna & Nozik, J Appl Phys. 100:074510-074517, 2006. Hou, et al., Nature Materials. 10:434-438, 2011. Idriss & Wahab, European Patent Serial Number 12006217.9, 2012. Jaramillo, et al., Science. 317:100-103, 2007. Jayaweera, et al., J Phys Chem. 111:1764-1769, 2007. Kudo & Miseki, Chem Soc Rev. 38:253-278, 2009. Linic, et al., Nature Materials. 10:911-921, 2011. Lu, et al., Environ Sci & Technol. 46:1724-1730, 2012. Maeda, et al., Energy Environ Sci. 3:471-477, 2010. Miller, et al., J Phys Chem. 101:2501-2507, 1997. Muggli & Falconer, J Catal. 187:230-237, 1999. Murdoch, et al. Nature Chemistry. 3:489-492, 2011. Nadeem, et al., J PhotoChem & PhotoBio A: Chemicals. 216:250-255, 2010. Ogden & Williams, Int J Hydrogen Energy. 15:155-169, 1990. Ogisu, et al., Chem Lett. 36:854-855, 2007. Sabio, et al., Langmuir. 26:7254-7267, 2010. Sartorel, et al., Energy Environ Sci. 5:5592-5603, 2012. Seh, et. al., Adv Mater. 24:2310-2314, 2012. Wilson & Idriss, J Am Chem Soc. 124:11284-11285, 2002. Wilson & Idriss, J Catal. 214:46-52, 2003. Yablonovitch, Phys Rev Lett. 58:2059-2062, 1987. Yamada, et al., Appl Phys Lett. 95:121112-121112-3, 2009. Zhang, et al., Nano Lett. 13:14-20, 2013. Zhou, et al., Langmuir. 20:1524-1526, 2004. Zhou, et al., Langmuir. 21:4717-4723, 2005. | Disclosed is a photocatalyst, and methods for its use, that includes a photoactive material comprising a photonic band gap and an electronic band gap, wherein the photonic band gap at least partially overlaps with the electronic band gap, and an electrically conductive material deposited on the photoactive material. | 1 |
CROSS-REFERENCE TO RELATED APPLICATIONS
The present application is a continuation-in-part of U.S. patent application Ser. No. 11/439,831 filed on May 23, 2006, the disclosure of which is incorporated by reference.
BACKGROUND OF THE INVENTION
This application relates to the field of compressed paper and woven goods.
Products made in a compressed state are small, for example, the size of a coin or a button. When such products are put into a liquid, for example, water, they expand, become larger, and are then suitable for their intended purpose. For example, buttons of compressed paper can be hydrated to be used as wipes. In other examples, compressed fabrics are hydrated to make towels, face cloths, tee shirts, and other clothing. Compressed sponges that expand upon contact with water are another example.
Compressed goods are useful because their light weight and small size make shipping and handling them easier than otherwise. There is a need to provide compressed goods with enhanced features, for example, ones that provide medicinal or comfort therapies.
SUMMARY OF THE INVENTION
In one aspect of the invention, microencapsulated materials are added to compressed products. Generally, the materials are added to the products before the products are compressed. The microencapsulated products can also be added to the products after they have been compressed.
Microencapsulation permits a wide range of products to be incorporated into these dehydrated compressed products while maintaining the dry, compressed nature of the products. The coatings of microencapsulated beads of material can be soluble in various types of liquid, for example, water. Moreover, in some examples, it may be desirable that the coatings only release material upon mechanical force, e.g., friction.
Methods of making an article are provided, the methods comprising forming the article, that comprises paper or fabric, in a size of intended use; attaching a plurality of microencapsulated beads containing a material therein to the paper or fabric; and compressing the article to a compressed size that is smaller than the size of intended use. In one embodiment, the step of compressing the article comprises dehydrating the article. In another embodiment, the step of compressing the article comprises exposing the article to vacuum pressure. In yet another embodiment, the method further comprises contacting the article with a liquid to expand the article to approximately the size of intended use.
In another aspect of the invention, the articles comprise a liquid-expandable paper or fabric, and a plurality of microencapsulated beads containing a material therein attached to the paper or fabric. Generally, the paper or fabric material is in a compressed state and the material remains compressed until a liquid contacts the material. This application may refer to the compressed paper or cloth as a compressed coin. In some examples, the microencapsulated beads are attached to the surface of the paper or fabric. In other examples, the beads are embedded within the fabric or paper.
In one embodiment, the material is released from the beads upon expansion of the paper or fabric in the liquid. In some examples, the material comprises therapeutic compounds such as antibiotics or alcohols, to be used, for example, for cleaning wounds or other medicinal purposes. Articles having such materials can be useful in military or third world environments. In other examples, the material comprises comforting compounds such as a fragrance, an oil, salt, a vitamin, a skin-moisturizer, or combinations thereof. Articles having such materials can be used as compresses for aromatherapy or other relaxation therapies. In another embodiment, the materials can be in the form of a hardening facial mask. These materials can be in the form of clay, resin, or other material that is pliable when wet but hardens upon drying.
In some embodiments, articles in accordance with the present invention comprise a towel, a face cloth, or a wiping cloth. If the article is used as a facial mask, it is supplied with cut-outs for the eyes, nose and mouth.
There are many uses for the micro encapsulated products in accordance with various aspects of the present invention. One use is combining the compressed coins with coated alcohol or antibiotic. When they are expanded, they then have the ability to be able to be used to clean wounds and other medical uses. This might be of particular value in third world areas or military situations.
Another use is to microencapsulate fragrances and/or oils with these compressed coins. In this application, these coins would be placed in warm water. As they are expanded they can be used as compresses for aromatherapy or other relaxation therapies.
It is believed that there are substantial uses and a substantial business for combining these two technologies. Without the dryness of the microencapsulation it would cause the coins to expand and/or the ingredients to be dissipated.
The articles can be packaged and sold individually, or in groups. In one embodiment, a plurality of similar articles are packaged in a strip, with each coin individually sealed in the strip. Thus, a single coin could be cut off of the strip without affecting the seal of the others, so that they are not exposed to air when removing a single coin. The strip could be formed from a plastic material that can be colored or printed to indicate the contents of the strip. The strip could have perforations along the seam to make separation easier. The strip could also have a weakening line extending to the area enclosing each coin to allow tearing of the packaging along the weakening line.
BRIEF DESCRIPTION OF THE DRAWINGS
Other objects and features of the present invention will become apparent from the following detailed description considered in connection with the accompanying drawings. It is to be understood, however, that the drawings are designed as an illustration only and not as a definition of the limits of the invention.
In the drawings, wherein similar reference characters denote similar elements throughout the several views:
FIGS. 1 and 2 illustrate a compressed cloth having microencapsulated beads in accordance with various aspects of the present invention.
FIG. 3 illustrates a method in accordance with one aspect of the present invention.
FIG. 4 illustrates the article in the form of a facial mask.
FIG. 5 illustrates several of the compressed articles in a strip of packaging.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now in detail to the drawings and, in particular, FIG. FIG. 1 illustrates one aspect of the present invention. Article 10 is paper, a woven good or cloth. The article 10 can, for example, be made of rayon, but any compressible material can be used.
Microencapsulated beads or materials 16 are added to the article 10 by known techniques to form a new article 12 . The microencapsulated beads 16 can be formed to be soluble in a liquid, such as water. In this case, the microencapsulated beads 16 will dissolve upon contact with the liquid and, upon being dissolved, will release the encapsulated material in the beads 16 . The microencapsulated beads 16 can also be formed to break upon a pressure or friction being asserted on the beads 16 . In this case, the beads 16 will break and release their contents upon the exertion of the pressure.
The article 12 having the microencapsulated beads can be compressed to a smaller size, such as the size of article 14 , using any known technique, the techniques including but not limited to dehydration or submitting the article 14 to vacuum pressure. The size of the article 12 is usually small, such as the size of a coin or a button. Other sizes, however, can be used.
The materials in the microencapsulated beads 16 can include an antibiotic, a pharmaceutical, an alcohol, a fragrance, an oil, vitamin, a salt, a skin conditioner, a skin moisturizer, or combinations thereof. Other materials can include cleansers, polishes, anti itch materials and anti-inflammatory materials.
Any number of fragrances can be used. For example, aromatherapy fragrances thought to help calm people can be used. A bubble gum fragrance can also be used to provide a unique bubble bath for children.
FIG. 2 illustrates the article 14 being exposed to a liquid 20 . The liquid 20 can be any liquid that will de-compress the article 14 . By way of example, the liquid could be water. The liquid 20 , in this case, also preferably dissolves the microencapsulated beads 16 to release the contents of the beads.
The result of the application of liquid 20 is that the article 14 expands to the size of the article 22 . The microencapsulated beads 16 have dissolved, releasing the contents 24 and 26 . Generally, if the contents of the beads 16 were in liquid form, the contents 24 will stay on the article 22 . If the contents of the beads 16 included fragrances, the contents 26 may leave the article 22 .
In the case where the microencapsulated beads 16 are broken by friction, the application of the liquid 20 would not dissolve the beads 16 . Instead, when the article 22 is rubbed on another article, such as a person's skin, the beads 16 are broken and the contents 24 and 26 are released.
The article 10 can be any compressible material that can be expanded.
FIG. 3 illustrates a method in accordance with one aspect of the present invention. In step 30 , microencapsulated beads are added to an article. As stated before, the article can be cloth, a woven material, paper or any compressible material. In step 32 , the article is compressed. The order of these two steps can be reversed.
In step 34 , the article is expanded. In step 36 , the contents of the microencapsulated beads 16 are released either as a result of contact with a liquid or as a result of friction or pressure.
The articles of the present invention can be used, by way of example only, to treat wounds, to provide therapy, such as aroma therapy or relaxation therapy, for bubble baths, for cleaning—both personal and for objects.
In accordance with another aspect of the present invention, the article 10 that is compressed can also be shaped. The article 10 can also have printed material on it. The shape of the article 10 and the printed material preferably have a relation to the article 10 and the material released by the microencapsulated beads 16 . For example, if the article 10 is a wash cloth and the microencapsulated material is a bubble gum fragrance so that a child might enjoy a bath, the article 10 can be shaped like a cartoon character and a picture of the carton character can be printed on the article 10 . For example, the article 10 could be shaped like Mickey Mouse and a picture of Mickey Mouse could be placed on the article 10 .
FIG. 4 shows another embodiment of the invention, in which article 100 is configured as a facial mask. Article 100 is compressed into a coin via vacuum compression, and expands into a facial mask shape, with cutouts 101 , 102 , 103 for the face, when contacted by liquid 180 . Embedded into article 100 is a microencapsulated facial mask material 150 that is beneficial to the skin and hardens upon drying. Any suitable mask material could be used, such as clay, resin or other synthetic or organic materials. Application of article 100 to a face 190 allows article 100 to mold to the shape of the face and dry thereon, thus providing beneficial treatment to the skin.
FIG. 5 shows a strip 200 of compressed articles 10 , which have been compressed into coin shape and are individually sealed in strip 200 in between sealed seams 215 . Strip 200 can be decorated or colored to match the type of material embedded within article 10 . In order to use an article 10 , the portion of strip 200 adjacent article 10 is cut or ripped away from the rest of strip 200 . Since each article 10 is individually sealed along seams 210 , the remaining articles 10 stay sealed. Perforations 216 can be placed along seams 215 to make separation of each article 100 easier. A weakening line 218 can extend into the space between seams 215 to make tearing of the packaging easier when accessing article 100 .
While there have been shown, described and pointed out fundamental novel features of the invention as applied to preferred embodiments thereof, it will be understood that various omissions and substitutions and changes in the form and details of the device illustrated and in its operation may be made by those skilled in the art without departing from the spirit of the invention. It is the intention, therefore, to be limited only as indicated by the scope of the claims appended hereto. | A compressed article of hygiene is formed by a compressed cloth that has been compressed by dehydration or vacuum pressure into a coin shape and that is expandable upon contact with a liquid, and a plurality of microencapsulated beads containing a material. The microencapsulated beads are attached and embedded in the compressed cloth. Upon contact with water, expansion of the compressed cloth is unconstrained, and the compressed cloth when expanded has a shape of a facial mask with openings for eye, nose and mouth. The material is a facial treatment material that hardens upon drying. | 0 |
CROSS-REFERENCES TO RELATED APPLICATIONS
The present application claims the priorities of Patent Cooperation Treaty Application No. PCT/EP2009/060472, filed on Aug. 13, 2009; European Patent Application No. 09154271.2, filed Mar. 4, 2009; and Patent Cooperation Treaty Application No. PCT/EP2008/067895, filed Dec. 18, 2008; all of which are incorporated herein by reference in their entirety for all purposes.
FIELD OF THE INVENTION
The present application concerns methods and facility systems for providing storable and transportable carbon-based energy carriers by application of carbon dioxide as a carbon supplier and by application of electric energy.
BACKGROUND OF THE INVENTION
Carbon dioxide CO 2 (often called carbonic acid gas) is a chemical compound composed of carbon and oxygen. Carbonic acid gas is a color- and odorless gas. It is a natural component of the air, with a low concentration, and is produced by in animals during the cell respiration, but also during the combustion of carbon-containing substances under sufficient presence of oxygen. Since the advent of the industrialization, the CO 2 proportion in the atmosphere has risen markedly. A main cause for this are the CO 2 emissions caused by human beings—the so-called antroprogenic CO 2 emissions. The carbonic acid gas in the atmosphere absorbs a portion of the heat radiation. This property renders carbonic acid gas to be a one of the so-called Green House Gases (GHG) and is one of the co-originators of the global greenhouse effect. For these and also for other reasons, research and development is performed at present in the most different directions to find a way to reduce the antroprogenic CO 2 emissions. In particular, in relation with the generation of energy which is often carried out by the combustion of fossil energy carriers such as coal, oil or gas, but also by other combustion processes, for example waste incineration, there is a great demand for CO 2 reduction. Per year, more than twenty billion tons of CO 2 are released into the atmosphere by such processes.
Among others, the principle of climate neutrality is aimed at by pursuing approaches in which efforts are made to compensate the generation of energy accompanied by CO 2 emissions by using alternative energies. This approach is represented in FIG. 1 in a very schematic manner. Emitters of greenhouse gases (GHG), such as industrial enterprises (e.g. manufacturers of automobiles) 1 or power plant operators 2 , invest in or operate, e.g. wind farms 3 at other locations in the framework of compensation projects to generate energy there without GHG emissions. Purely on the basis of calculations, it is thus possible to achieve climate compensation. Numerous companies try to buy a “climatically neutral” profile in this way.
Wind and solar power plants which convert the renewable energies into electric energy have an unsteady delivery of power, which hampers the operation of a facility according to the requirements of an electrically mixed network and gives rise to facility and operation costs for additional reserve and frequency regulation facilities. Accordingly, the costs of power generation from wind or solar power plants are thereby raised significantly compared to conventional power.
It is seen as a problem that at present almost all regenerative electric energy that is produced is supplied to the public AC voltage mixed network, the frequency of which is allowed to vary only within very narrow boundaries (e.g., +/−0.4%). This can only be achieved when the generation of electric current in the network is virtually always equal to the consumption. The necessity that wind and solar power plants must always hold available the sufficient reserve and frequency regulation capacities leads to an increase in the costs of power generation with these facilities. Wind and solar power plants within the electrical mixed network thus result in further “hidden” costs and problems.
Already at the present stage of completion of wind power plants in many countries, the electric power supply network may create serious problems, if, e.g., as a result of wind scarcity or strong winds, wind power fails at a large scale, in particular if this failure occurs suddenly or unexpectedly. In any case however, reserve and frequency regulation capacities are necessary, which are adapted to the installed wind and solar output.
It follows from the above that solar and wind power plants which supply (current) into an electrical mixed network can hardly replace the installed outputs of other power plants in the mixed network. This leads to a situation that solar and wind power may be valuated approximately only with the saved fuel cost of the other heat power plants present in the network.
SUMMARY OF THE INVENTION
Now it is seen as an object to provide a method that is capable to generate storable hydrocarbon-based energy carriers, for example as fuels or combustibles. The provision of these energy carriers should be accomplished with an additional emission of CO 2 that is as low as possible, and the application of these energy carriers should contribute to a reduction of the CO 2 emission.
According to the invention, a method and a facility system (device) for providing storable and transportable energy carriers are provided.
According to a first embodiment of the invention, carbonic acid gas is utilized as a carbon supplier. Preferably, the carbonic acid gas is extracted from a combustion process or from an oxidation process of carbon by means of CO 2 precipitation. Electric direct current (DC) energy is provided. This DC energy is generated largely by means of renewable energies, and it is utilized to perform an electrolysis so as to generate hydrogen as an intermediate product. The carbonic acid gas is then brought to a reaction with the hydrogen so as to transform these products to methanol or to another hydrocarbon.
In another preferred embodiment, a transformation takes place in a reduction process from a silicon-dioxide-containing starting material to silicon, whereby the energy for this reduction process is provided to a large extent from renewable energies. A portion of the reaction products of this reduction process is then used in the process for generating methanol, wherein in this methanol generating process, a synthesis gas of carbonic acid gas and hydrogen is used. The conversion from a silicon-dioxide-containing starting material to silicon can be performed as an additional method step.
According to the invention, a facility system operation is prepared which is as constant and long-term as possible, and this is achieved by the addition to the supply of regenerative power of a conventional (e.g., fossil) supply of power from a mixed network. Preferably, according to the invention, the conventional power supply is tied in during the low-load period of the electrical mixed network. This means that, e.g., a wind and/or solar power plant and the plant according to the invention are tied mutually with the existing electrical mixed network in a way that is economically and ecologically optimized as far as possible, such that
the total yield of the reaction products becomes as large (maximal) as possible; and/or the CO 2 emission becomes as low (minimal) as possible; and/or a capacity utilization of the facility is achieved that is as constant and long-term as possible; and/or the product specific costs of investment and operation of the regenerative power plant and of the plant of the present invention become as low (minimal) as possible.
According to the invention, the electric energy from wind and/or solar power plants is not supplied to a mixed network, but is converted directly to storable and transportable energy forms (preferably hydrocarbons, such as e.g. methanol). That is, the renewable energies are converted into storable and transportable energy forms in a chemical way.
It is a further advantage of the conversion to storable and transportable energy forms that the energy conversion efficiency is raised, because in photovoltaic plants, no alternating current (AC) converters for generating an alternating voltage are required and transport over a large distance of the electric energy through long high voltage lines is generally not required.
The generation costs of the renewable electric energy from solar and wind power plants will be relatively high for a conceivable time. This results in a direct usage of such electric energy for chemical processes, as proposed herein, the chemical products are more expensive than the conventionally fabricated products—fabricated generally using fossils. This holds in particular, when the real environmental damages caused, e.g., by a fossil power plant, are not internalized, i.e., taken into account in the total balance.
In order to avoid this disadvantage, in the plant according to the invention, creates a combination of regenerative and a conventional power supply which is as economically and ecologically optimized as possible in networking with an available electrical mixed network. The plant concept therefore conceives in a preferred embodiment to use regenerative electric energy according to its production and electric energy from an electrical mixed network primarily in the low-load periods thereof for chemical reactions and thus to also store it. In periods of electrical peak power demands in the electrical mixed network, the regenerative energy can be supplied also to the mixed network—to achieve higher proceeds. This supply is optional.
Instead of supplying the regenerative electric energy from wind and/or solar power plants which evolves unsteadily to an electrical mixed network and of balancing and regulating their variations and failures by means of other power plants or storage facilities, the electric energy from wind or solar power plants is preferably used to operate a chemical plant of the present invention so as to generate storable and transportable energy forms. In the case that where a plant of the present invention is tied to a mixed network in order to extract a portion of the electric energy from the mixed network, a presently available excess energy portion can be extracted from the mixed network by means of an intelligent facility regulation or control, while the remaining required energy portion is taken from the solar and/or wind power plant associated with the plant. Thereby, an intelligent reversal of the existing principle is achieved, in which the variations of the regenerative power from wind and/or solar power plants must be buffered tying in conventional power plants and/or storage facilities. For operating a plant of the present invention, it is therefore not necessary to hold available any regulation and power reserves in the electrical mixed network. This principle leads to significant reduction of costs and enables a user to take into account additional technical and economical parameters in the control of the plant.
In addition, the regulation and control of the power supply of the plant becomes significantly simpler and more reliable, since the decision taking authority thereon rests in the range of responsibilities of the operator of the plant. In a conventional mixed network, which takes electric current from renewable energy facilities and conventional plants, numerous partners are involved, and this makes the tying in of the facilities with respect to the regulation and control technology and the decision making very complex, which also lead to supply failures in the recent past.
The production of the storable and transportable energy forms can be shut-down or even interrupted at any time. This happens preferably in cases when a peak energy demand exists in the electrical mixed network. The “chemical part” of the of the present invention can be shut-down or switched off relatively easily and quickly. Also here, the decision taking authority rests in the range of responsibilities of the operator of the plant of the present invention.
The energy form which is provided by the chemical plant of the present invention can serve as an additional energy buffer. Thus, methanol can be stored, for example, in order to provide additional electric power to the electrical mixed network during peak power demands. Methanol can be combusted on request, for example, in heat power plants, or electric energy can be generated therewith in fuel cells (e.g., direct-methanol fuel cells, called MFC).
The present invention is also based on the generation of hydrogen with the aid of electric energy largely taken from wind and/or solar power plants in combination with the direct conversion of the hydrogen to a hydrocarbon. Hydrogen is thus not stored or highly condensed or cooled and transported over large distances, but serves as an intermediate product that is converted at the site of its generation. According to the invention, substance-converting (chemical) processes, notably the intermediate provision of hydrogen and the conversion of the hydrogen together with carbonic acid gas to a hydrocarbon (e.g., methanol) follow an energy-converting process, in which solar energy or wind energy is converted into electric energy.
Taking into account standards in energy technology, facility technology and economics, together with the demand for a preserving use of all material, energetical and ecological resources, a new solution in energy technology is provided according to the invention.
Further advantageous embodiments can be taken from the description, the Figures and the dependent claims.
BRIEF DESCRIPTION OF THE DRAWING
In the drawings, different aspects of the invention are represented schematically, wherein:
FIG. 1 : shows a scheme representing the principle of climate neutrality by the investment in or the operation of compensation projects;
FIG. 2 : shows the basic steps of a first method to create a chemical plant of the present invention;
FIG. 3 : shows the basic steps of a second method of creating a chemical plant according to the invention;
FIG. 4 : shows the basic steps of a further method of creating a chemical plant according to the invention;
FIG. 5 : shows the steps of a further partial method according to the invention; and
FIG. 6 : shows a scheme illustrating the steps of a further partial method according to the invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The method according to the invention is based on a new concept, which by using available starting materials provides so-called reaction products that are either directly usable as an energy carrier or that are indirectly usable as energy carriers, i.e. after performing additional intermediate steps.
The term energy carrier is used herein to designate compounds, which may either be used directly as a fuel or combustion material (such as, e.g., methanol 108 ) and also compounds (such as, e.g., silicon 603 ), which have an energy content or an elevated energy level and which can be converted in further steps with delivery of energy (refer to energy E 3 in FIG. 6 ) and/or with delivery of a further energy carrier (such as, e.g., hydrogen 103 ).
The transportability of the energy carrier is herein characterized by the chemical reaction potential.
In the case of hydrocarbons (such as methanol 108 ) being used as an energy carrier, specific framework conditions should be respected during its storage and transport, which conditions are similar to the conditions for the handling of fossil fuels. In this respect, the existing infrastructure can be used without problems. Specific adaptations may be required only as far as the compounds are concerned.
In the case of silicon 603 being used as an energy carrier, specific framework conditions should be respected during its storage and transport so as to avoid initiating an undesired or uncontrolled reaction (oxidation) of the silicon. The silicon 603 should be stored and transported preferably in a dry state. In addition, the silicon 603 should not be heated because otherwise the probability of a reaction with water vapor from the ambient air or with oxygen rises. Investigations have shown that up to approximately 300° C., silicon has very little tendency to react with water or oxygen. The storage and transport of the silicon 603 together with a water getter (i.e., a compound that is hydrophillic/attracting water) and/or an oxygen getter (i.e., a compound that is attracting oxygen) is ideal.
The term silicon-dioxide-containing starting material 601 is used herein to designate compounds which contain a large proportion of silicon dioxide (SiO 2 ). Sand and shale (SiO2+[CO 3 ] 2 ) are particularly suitable. Sand is a naturally occurring non-consolidated sedimentary rock and occurs everywhere on the surface of the Earth in large concentrations. A majority of the occurances of sand consist of quartz (silicon dioxide, SiO 2 ).
According to a first embodiment of the invention, carbonic acid gas 101 is used as a carbon supplier, as indicated schematically in FIG. 2 . The carbonic acid gas 101 is preferably extracted from a combustion process 201 (symbolized by a fire in FIG. 3 ) or from an oxidation process through CO 2 precipitation (e.g., a Silicon-Fire flue gas cleaning facility 203 ). Furthermore, electric DC power E 1 is provided. The DC power E 1 is produced regeneratively (e.g., by one of the facilities 300 or 400 in FIG. 4 ). The DC energy E 1 is used to carry out an electrolysis so as to generate hydrogen 103 as an intermediate product. The electrolysis facility, which carries out such electrolysis, is characterized in FIG. 2 by the reference numeral 105 . The carbonic acid gas 101 is then brought to reaction with the hydrogen 103 (e.g., by a synthesis of methanol) so as to convert the (intermediate) products 101 , 103 to methanol 108 or to another hydrocarbon. The reaction can be carried out in a reaction containment 106 , and the extraction of the methanol is characterized in FIG. 2 by the reference numeral 107 .
In the following, further basic details of this method and the corresponding plant 100 are described.
A water electrolysis with an application of DC current E 1 is suitable in order to be able to generate hydrogen 103 as an intermediate product. The required hydrogen 103 is produced in an electrolysis facility 105 by the electrolysis of water H 2 O:
H 2 O−286.02 kJ=H 2 +0.5O 2 (Reaction 1)
The required (electric) energy E 1 for this reaction amounting to 286.02 kJ mol corresponds to 143,000 kJ per kg H 2 .
The synthesis of the methanol 108 (CH 3 OH) proceeds in the Silicon-Fire plant 100 after the exothermal reaction between carbonic acid gas 101 (CO 2 ) and hydrogen 103 (H 2 ) as follows:
CO 2 +3H 2 ═CH 3 OH+H 2 O−49.6 kJ(gaseous methanol) (Reaction 2)
The generated reaction heat energy W 1 amounting to 49.6 kJ/mol=1,550 kJ per kg methanol=0.43 kWh per kg methanol, is extracted from the corresponding synthesis reactor 106 . Typical synthesis conditions in the synthesis reactor 106 are approximately 50 bar and approx. 270° C., so that the reaction heat energy W 1 can also be used for, e.g., a nearby seawater desalination facility or a heating plant.
Preferably, the synthesis of methanol is performed by application of catalysts in order to keep the reaction temperature and pressure as well as the reaction duration low and in order to ensure that high-value (pure) methanol 108 is generated as the reaction product.
In another preferred embodiment of the invention, a synthesis of methanol according to an electrolysis method propagated by Prof. George A. Olah is carried out. Details thereon can be taken, for example, from the book “Beyond Oil and Gas: The Methanol Economy”, George A. Olah et al., Wiley-VCH, 1998, ISBN 0-471-14877-6, chapter 11, page 196. Further details can also be taken from the US patent application US 2009/0014336 A1. Prof. George A. Olah describes the synthesis of methanol by the electrolysis of CO 2 and H 2 as follows:
CO 2 +2H 2 O−682.01 kJ=CH 3 OH+1.5O 2 (Reaction 3)
In this reaction, CO and H 2 are generated in an intermediate step in a ratio of about 1:2. The CO and H 2 that is generated at a cathode, can be converted to methanol using a copper- or nickel-based catalyst. The synthesis path according to reaction 3 is related to a theoretical addition of 682.01 kJ=0.189 kWh of electric energy per mol of methanol 108 produced.
In the case that the plant of the present invention is located in the vicinity of a CO 2 source, it is possible to refrain from a liquefaction for the transport of CO 2 . Otherwise, it is relatively easy according to the state of the art, to liquefy the CO 2 and to bring it to a plant of the present invention 100 . In case of a renunciation of the liquefaction, and where necessary for storage and transport over large distances, the CO 2 is available in a conceivably cost-neutral way by accounting for CO 2 avoidance credits. Also in the case of a transport, the costs for the “buying” of the CO 2 are relatively low.
In FIG. 3 , further steps of a first method according to the invention, respectively a part of a Silicon-Fire plant 200 are shown. The carbonic acid gas 101 is, as already mentioned, preferably extracted from a combustion process 201 (here characterized by a fire) or from an oxidation process by means of CO 2 precipitation, e.g., with a Silicon-Fire flue gas treatment facility 203 . The Silicon-Fire flue gas treatment facility 203 can be constructed, for example, according to the principle of the cleaning of flue gas, wherein the CO 2 is “washed out” from the flue gas 202 using a cleaning solution. A flue gas cleaning which uses NaOH as a cleaning solution and in which the NaOH is recycled, is particularly suitable for a flue gas cleaning. Details thereon can be taken, for example, from the parallel application EP 1 958 683 filed on 7 Aug. 2007. However, other principles of CO 2 precipitation or production can also be used.
The Silicon Fire flue gas cleaning facility 203 allows extracting CO 2 (herein called a resource) from the flue gas 202 . This CO 2 is then supplied directly or indirectly to the Silicon-Fire plant 100 which then generates/synthesizes a hydrocarbon (preferably methanol 108 ) under application of the CO 2 as a carbon supplier and under application of electric power.
FIG. 4 shows, in a schematic block diagram, the most important modules/components for the method steps of a Silicon-Fire plant 100 . This plant 100 is designed such that a method for providing storable and transportable energy carriers 108 can be carried out. The corresponding method is based on the following basic steps.
Carbonic acid gas 101 is provided as a carbon supplier, as already described. The required electric DC power E 1 is produced using renewable energy technology and is supplied for use to the Silicon-Fire plant 100 . Solar heat plants 300 and photovoltaic plants 400 which are based on solar modules are particularly suitable as renewable energy technology. It is also possible to arrange a combination of these types of plants 300 and 400 since the demand per area in relation to the electric power from the solar thermal plant 300 is less than that from a photovoltaic plant 400 .
According to the invention, an electrolysis 105 is carried out under application of the electric DC energy E 1 so as to produce hydrogen 103 or hydrogen ions as an intermediate product. The electrolysis 105 can be carried out according to the following three different approaches:
either a direct water electrolysis according to Reaction 1 as represented in FIG. 4 is performed, or silicon is produced from a silicon-dioxide-containing composition in an electrolytic way, where the silicon then reacts with water 102 to produce hydrogen 103 and silicon dioxide in a subsequent (downstream) hydrolysis reaction, or methanol 108 is directly produced (refer to Reaction 3) in an electrolytic way, wherein intermediate hydrogen such as hydrogen ions are generated, which react, however, directly with the other ions or reaction partners to form methanol 108 .
In the methods which do not produce methanol 108 directly in an electrolytic way, hydrogen 103 and carbonic acid gas 101 are brought together in the plant 100 so as to convert these in a reaction 106 to methanol 108 or to another hydrocarbon. The methanol 108 may then be extracted from the plant 100 , as represented by the arrow 107 .
In FIG. 4 , a particularly preferred plant 100 is represented, which is constructed such that the initially mentioned disadvantages are reduced or compensated. For this reason, an economically and ecologically optimal combination of regenerative electric power supply (by the plants 300 and/or 400 ) and conventional power supply, here represented as a part of a mixed network 500 , are realized using the Silicon-Fire plant according to the invention. In a preferred embodiment, the Silicon-Fire plant 100 therefore enables the regenerative electric energy E 1 to be used for chemical reactions (here the electrolysis reaction 105 ) and thus to store it. A further portion of the required energy is taken from the mixed network 500 . This portion is converted into DC energy E 2 . To this end, an according converter 501 comes into operation, as indicated in schematic form in FIG. 4 . The corresponding facility parts or components are herein referred to as the energy supply plant 501 .
The energy supply of the plant 100 is controlled and regulated by means of an intelligent facility control device 110 . In principle, the respective excess energy portion E 2 that is presently available is taken from the mixed network 500 , while the other energy portion (here E 1 ) is taken as largely as possible from a solar power plant 300 and/or 400 (or from a wind farm) associated with the plant. Accordingly, an intelligent reversal of the hitherto used principles is realized, in which the energy variations of renewable energy facilities 300 , 400 are buffered by tying in and out (switching on and switching off) conventional facilities. For operating a Silicon-Fire plant 100 , it is therefore not required to hold available additional power and frequency regulation capacities for the regenerative power plants in the mixed network 500 . This principle allows the operator of a Silicon-Fire plant 100 to take into account additional technical and economical parameters in the control of the plant 100 . These parameters concern so-called input parameters I 1 , I 2 , etc., which are tied in by the control device 110 when taking decisions. Some of these parameters can be predefined within the control device 110 in a parameter storage 111 . Others of the parameters can be supplied from the outside. Here, for example, information on price and/or availability from the operator of the mixed network 500 may be input.
In the facility control device 110 , so-called software-based decision processes are implemented. A processor of the control device 110 executes a control software and takes decisions by accounting for parameters. These decisions are transformed into switch or control instructions, which cause the control/regulation of energy and mass fluxes, for example, through the control or signal lines 112 , 113 , 114 .
Considered from the perspective of the mixed network, the Silicon-Fire plant 100 concerns a consumer, which can be switched-on and off quickly and which can be used relatively flexible. If, for example, a sudden additional demand of electric energy occurs in the mixed network, then the control device 110 can shut down or switch off completely the portion E 2 . In this case, from that moment on, either accordingly less hydrogen 103 is produced whence energy E 1 is available, or the electrolysis is temporarily stopped completely.
In FIG. 4 it is indicated by means of dashed arrows 112 which begin at the control device 110 that the control device 110 regulates the energy fluxes E 1 and E 2 . The arrows 112 represent control or signal lines. Also other possible control or signal lines 113 , 114 are represented. For example, the control or signal line 113 regulates the amount of CO 2 that is available for the reaction 106 . If, for example, less hydrogen 103 is produced because no energy E 2 is available, then also less CO 2 must be supplied. The optional control or signal line 114 can, for example, regulate the amount of H 2 . Such a regulation makes sense, for example, in cases where there is a hydrogen buffer storage, from which hydrogen 103 can be drawn, even where there is less hydrogen or no hydrogen at all is produced momentarily by the electrolysis 105 .
Investigations have shown that it is particularly economical and advantageous in an environmental sense if the Silicon-Fire plant 100 extracts between 15% and 50% of the electric energy requirement from solar energy and the remaining energy requirement from the mixed network 500 (i.e., mainly fossil). It is particularly preferable to cover between 30% and 40% of the electric energy requirement from solar energy and the remaining 70% to 60% from the mixed network 500 (i.e., mainly fossil). The intelligent facility control device 110 is set or programmed according to these specifications.
An embodiment of the plant 100 , which provides for the extraction of cheap electric energy from the mixed network 500 in low-load periods, is particularly preferred.
According to a preferred embodiment of the invention, the facility control device 110 is set or programmed such that the networking between regenerative electric energy sources 300 and/or 400 and the electrical mixed network 500 is optimized such that the total costs of electric energy becomes minimal for maximum usage of the regenerative electric energy sources 300 and/or 400 .
According to a preferred embodiment of the invention, the facility control device 110 is set or programmed such that the networking between regenerative electric energy sources 300 and/or 400 and the electrical mixed network 500 is optimized such that the total costs of the carbonic acid gas product 108 becomes minimal for a maximum usage of the regenerative electric energy sources 300 and/or 400 and by taking into account the total costs of the electric power and the periods of capacity utilization by operation of the whole plant 100 and its facility parts.
According to a preferred embodiment of the invention, the facility control device 110 is set or programmed such that the networking between the regenerative electric energy sources 300 and/or 400 and the electrical mixed network 500 is optimized such that revenues are gained by temporarily supplying (emerging from) the regenerative energy sources 300 and/or 400 to the electrical mixed network 500 during its peak periods and that thereby the total costs of the electric power for the method according to the invention or the total costs of the carbonic acid gas product 108 are reduced or lowered as far as possible.
In periods of a peak electric power demand of the electrical mixed network 500 , the regenerative energy E 1 can also be supplied to the mixed network—to obtain higher revenues.
The aspects of these preferred embodiments can easily and without problems be combined by a corresponding design of the control device 110 .
In the following, further basic aspects of a method according to the invention for providing storable and transportable energy carriers are shown. In this method, silicon 603 as a first storable and transportable energy carrier and methanol 108 as a second storable and transportable energy carrier are provided. The method comprises at least the following steps.
By a transformation, a silicon-dioxide-containing starting material 601 is converted to elementary silicon 603 by means of a reduction process 602 , as shown in FIG. 5 . The elementary silicon 603 is herein called silicon for reasons of simplicity. The required electrical (primary) energy E 1 for this reduction process 602 is provided according to the invention from a regenerative energy source 300 . In a subsequent/downstream step, at least a portion of the silicon 603 can be utilized in a process for generating methanol. In this process, for example, a synthesis gas composed of carbonic acid gas 101 and hydrogen 103 comes into use in the process of generating methanol. The silicon 603 can also be extracted from the process as an energy carrier. The silicon 603 can, for example, be stored or transported away.
The transformation 602 is preferably an electrochemical electrolytical transformation (with participation of an electrical current E 1 ), as schematically indicated in FIG. 5 .
In the electrochemical transformation 602 according to FIG. 5 , the (primary) energy E 1 for the transformation is provided in the form of electric current which is generated from sunlight. For the electrochemical transformation 602 , a solar plant 300 is utilized, as indicated schematically in FIG. 5 .
The electrochemical transformation 602 can, for example, be carried out by employing silicon dioxide as an electrode. A metal is employed as the second electrode. Calcium chloride (CaCl 2 ) is, for example, used as an electrolyte. This electrochemical transformation process 602 functions particularly well with an electrode made of porous silicon dioxide, which may, for example, be sintered from silicon dioxide. Details concerning this method can be taken from the following publications:
Nature Materials, June 2003; 2(6): 397-401, Nohira T., Yasuda K., Ito Y., Publisher: Nature Pub. Group. “New silicon production method with no carbon reductant”, George Zheng Chen; D. J. Fray, T. W. Farthing, Tom W. (2000). “Direct electrochemical reduction of titanium dioxide to titanium in molten calcium chloride”, George Zheng Chen, D. J. Fray, T. W. Farthing, Nature 407 (6802): 361-364, doi: 10.1038/35030069. “Effects of electrolysis potential on reduction of solid silicon dioxide in molten CaCl 2 ,” YASUDA Kouji, NOHIRA Toshiyuki, ITO Yasuhiko; The Journal of Physics and Chemistry of Solids, ISSN 0022-3697, International IUPAC Conference on High Temperature Materials Chemistry No. 11, Tokyo, Japan (19 May 2003), 2005, vol. 66, no. 2-4 (491 p.); U.S. Pat. No. 6,540,902 B1; WO 2006/092615 A1.
Preferably, a reduction process 602 is performed at a temperature of approximately 1900 K (=1630° C.) so as to reduce the silicon dioxide 601 to silicon 603 . In an electrochemical transformation 602 , however, considerably lower temperatures (preferably less than 500° C.) are required.
In relation with FIG. 6 , it is described how silicon 603 can be utilized as an energy carrier. The reduced silicon 603 is an energy-rich compound. This silicon has the tendency to oxidize with water in fluid or vapor form back again to silicon dioxide 604 (reverse reaction), as indicated schematically in FIG. 6 . In the so-called hydrolysis 605 of the silicon 603 , energy E 3 (e.g., heat energy) is liberated because this concerns an exothermal reaction. In addition to the silicon dioxide 604 , hydrogen 103 is formed, which can be utilized, for example, as an energy carrier for the generation of methanol 108 . Preferably, the hydrolysis 605 takes place at elevated temperatures. Temperatures are preferred which are clearly above 100° C. In the temperature range between 100° C. and 300° C., a conversion in usable quantities is achieved in cases when the silicon 603 is brought in contact and mixed in a very finely grained or powdery consistency with water vapor 102 . Since otherwise the silicon 603 has only a very low tendency to react with water up to approximately 300° C., the hydrolysis 605 is preferably performed in the temperature range between 300° C. and 600° C.
The hydrolysis can also be performed with aqueous hydroxide and alkali carbonate-solutions, for which preferably temperatures between 60° C. and 160° C. are used.
According to the invention, in a method according to FIG. 6 , the silicon 603 is introduced into a reaction area and mixed with water 102 in liquid or vapor form. In addition, according to the invention, care is taken that the silicon 603 has a minimum (threshold) temperature. Either the silicon 603 is heated for this purpose (e.g., using heating means or by heat-generating or heat-releasing additives) or the silicon 603 is already at a corresponding temperature level when it is introduced.
Under these framework conditions, hydrogen 103 is then liberated in the reaction area as a gas. The hydrogen 103 is extracted from the reaction area.
In the following, a quantitative example for a method according to FIG. 6 or according to FIG. 5 in combination with FIG. 6 is presented:
1 mol (=60.1 g) SiO 2 forms 1 mol (=28 g) Si.
1 mol (=28 g) Si in turn forms 1 mol (=451 g) H 2 . This means that 2.15 kg SiO 2 form 1 kg Si and froms this 1 kg Si in turn, 1.6 m 3 H2 are formed.
The generation of methanol can be carried out according to one of the methods known and used at large-scale. A method is preferred in which a catalyst (e.g., a CuO—ZnO—Cr 2 O 3 or a Cu—Zn—Al 2 O 3 catalyst) is used.
The invention has the advantage that in the reduction of the silicon dioxide and in the reduction of the water 102 , no CO 2 is liberated as long as only energy E 1 which originates from a plant 300 and/or 400 is utilized in these reactions. The required energy is therefore provided at least in part from renewable energy resources, preferably from the plants 300 and/or 400 .
In the hydrolysis 605 , the elementary silicon 603 is utilized preferably in a powder form or in a granular or grainy form.
According to the invention, CO 2 101 serves as a starting material and as a carbon supplier for the synthesis of methanol in the reactor 106 . Preferably, the following serve as a CO 2 source: steam reforming facilities, natural gas-CO 2 -separation facilities, cement plants, bio-ethanol plants, seawater desalination facilities, power plants and other facilities or combustion processors which emit large quantities of CO 2 .
The invention avoids the considerable economical disadvantages of known approaches, when—as in the case of the Silicon-Fire plant 100 —the electric solar and/or wind energy, which is produced unsteadily, is directly converted to chemical reactions and is stored in a chemically bound form, without the additional capacities for reserve power and/or frequency regulation in the mixed network.
In the case that photovoltaic current is generated by means of a photovoltaic plant 400 , there is a further advantage in that the DC current E 1 , which is primarily produced from the solar cells of the photovoltaic plant 400 , can be utilized directly in the chemical process (electrolysis 105 ), without having to be converted using converters to an alternating (AC) current for the voltage transformation.
LIST OF REFERENCE NUMERALS
car Industry/automotive Engineering
1
operator of Power Plant
2
wind farm
3
Silicon-Fire plant
100
carbon dioxide
101
water
102
hydrogen
103
providing carbon dioxide
104
carrying out an electrolysis
105
bringing together the hydrogen (H 2 ) and the carbon
106
dioxide/synthesis reactor
delivering/providing methanol
107
transportable energy carrier
108
(facility) control device
110
parameter storage
111
control or signal lines
112, 113, 114
Silicon-Fire partial facility
200
combustion process
201
flue gas comprising CO 2
202
Silicon-Fire flue gas cleaning facility
203
clean gas
204
flue free of CO 2
205
extraction of CO 2
206
solar thermal energy facility
300
conversion of heat to direct current
301
solar plant (photovoltaic plant)
400
mixed network
500
conversion of alternating voltage to direct current
501
(energy supply facility)
silicon-dioxide-containing starting material
601
silicon
603
reduction process
602
silicon dioxide as a reverse reaction product
604
hydrolysis
605
direct current (DC) energy
E1
additional electric power
E2
energy
E3
input parameters
I1, I2, etc.
primary energy
P1, P2
reaction (product) heat from the synthesis of methanol
W1 | The invention relates to methods and facility systems ( 100 ) for providing storable and transportable carbon-based energy carriers ( 108 ) by application of carbon dioxide ( 101 ) as a carbon supplier and by application of electric energy (E 1 , E 2 ). The facility system ( 100 ) comprises a plant ( 300, 301; 400 ) for providing a first portion of energy in the form of direct current energy (E 1 ) from renewable energy sources. In addition, a power supplies facility ( 501 ) is provided for tying the facility system ( 100 ) to a mixed network ( 500 ), wherein the power supplies facility ( 501 ) produces a second portion of energy in the form of direct current energy (E 2 ) from an alternating current voltage of the mixed network ( 500 ). A device ( 102, 105 ) is adapted to provide hydrogen ( 103 ), wherein a part of the energy requirement of this device ( 102, 105 ) is covered by said first portion of energy and another part is covered by said second portion of energy. A carbon dioxide supply serves for introducing carbon dioxide ( 101 ) and a reaction area ( 106 ) is provided for producing a hydrocarbon, preferably methanol ( 108 ). | 2 |
This is a National Phase filing under 35 U.S.C. §371 based on PCT/IB95/00448, which was filed internationally on Jun. 7, 1995.
FIELD OF THE INVENTION
This invention relates to compounds which are inhibitors of microsomal triglyceride transfer protein and/or apolipoprotein B (Apo B) secretion, and which are accordingly useful for the prevention and treatment of atherosclerosis and its clinical sequelae, for lowering serum lipids, and related diseases. The invention further relates to compositions comprising the compounds and to methods of treating atherosclerosis, obesity, and related diseases and/or conditions with the compounds.
BACKGROUND OF THE INVENTION
Microsomal triglyceride transfer protein (MTP) catalyzes the transport of triglyceride, cholesteryl ester, and phospholipids. It has been implicated as a probable agent in the assembly of Apo B-containing lipoproteins, biomolecules which contribute to the formation of atherosclerotic lesions. See European Patent application publication no. 0 643 057 A1, European Patent application publication no. 0 584 446 A2, and Wetterau et al., Science, 258, 999-1001, (1992). Compounds which inhibit MTP and/or otherwise inhibit Apo B secretion are accordingly useful in the treatment of atherosclerosis. Such compounds are also useful In the treatment of other diseases or conditions in which, by inhibiting MTP and/or Apo B secretion, serum cholesterol and triglyceride levels can be reduced. Such conditions include hypercholesterolemia, hypertriglyceridemia, pancreatits, and obesity; and hypercholesterolemia, hypertriglyceridemia, and hyperlipidemla associated with pancreatitis, obesity, and diabetes.
Examples of general information and/or documents defining the general state of the art include EP-A-0 635 492, J. Med. Chem. (1975) 18(12), 1227-1231, U.S. Pat. No. 4,022,900, and EP-A-0 106 140.
SUMMARY OF THE INVENTION
This invention provides compounds of formula I ##STR2## wherein X is CH 2 , CO, CS, or SO 2 ;
Y is selected from:
a direct link (i.e., a covalent bond),
aliphatic hydrocarbylene radicals having up to 20 carbon atoms, which radical may be mono-substed by hydroxy, (C 1 -C 10 )alkoxy, (C 1 -C 10 )acyl, (C 1 -C 10 )acyloxy, or (C 6 -C 10 )aryl,
NH, and O, provided that if X is CH 2 , Y is a direct link;
Z is selected from the following groups:
(1) H, halo, cyano,
(2) hydroxy, (C 1 -C 10 )alkoxy, (C 1 -C 10 )alkylthio, (C 1 -C 10 )acyl, thiophenylcarbonyl, (C 1 -C 10 )alkylcarbonyl,
(3) (C 1 -C 10 )alkylamino, di(C 1 -C 10 )alkylamino, (C 6 -C 10 )aryl(C 1 -C 10 )alkylamino, provided that Y is not O or NH,
(4) unsubstituted vinyl, (C 6 -C 10 )aryl, (C 3 -C 8 )cycloalkyl and fused benz derivatives thereof, (C 7 -C 10 )polycycloalkyl, (C 4 -C 8 )cycloalkenyl, (C 7 -C 10 )polycycloalkenyl,
(5) (C 6 -C 10 ))aryloxy, (C 6 -C 10 )arylthio, (C 6 -C 10 )aryl(C 1 -C 10 )alkoxy, (C 6 -C 10 )aryl(C 1 -C 10 )alkylthio, (C 3 -C 8 )cycloalkyloxy, (C 4 -C 8 )cycloalkenyloxy,
(6) heterocyclyl selected from the group consisting of monocyclic radicals and fused polycyclic radicals, wherein said radicals contain a total of from 5 to 14 ring atoms, wherein said radicals contain a total of from 1 to 4 ring heteroatoms independently selected from oxygen, nitrogen, and sulfur, and wherein the individual rings of said radicals may be independently saturated, partially unsaturated, or aromatic,
provided that if X is CH 2 , Z is H or is selected from groups (4) and (6),
wherein, when Z contains one or more rings, said rings may each independently bear 0 to 4 substituents independently selected from halo, hydroxy, cyano, nitro, oxo (O═), thioxo(S═), aminosulfonyl, phenyl, phenoxy, phenylthio, halophenylthio, benzyl, benzyloxy, (C 1 -C 10 )alkyl, (C 1 -C 10 )alkoxy, (C 1 -C 10 )alkoxycarbonyl, (C 1 -C 10 )alkylthio, (C 1 -C 10 )alkylamino, (C 1 -C 10 )alkylaminocarbonyl, di(C 1 -C 10 )alkylamino, di(C 1 -C 10 )alkylaminocarbonyl, di(C 1 -C 10 )alkylamino(C 1 -C 10 )alkoxy, (C 1 -C 3 )perfluoroalkyl, (C 1 -C 3 )perfluoroalkoxy, (C 1 -C 10 )acyl, (C 1 -C 10 )acyloxy, (C 1 -C 10 )acyloxy(C 1 -C 10 )alkyl, and pyrrolidinyl;
and pharmaceutically acceptable salts thereof.
Reference to Z as "heterocyclyl" means any single ring or fused ring system containing at least one ring heteroatom independently selected from O, N, and S. Thus a polycyclic fused ring system containing one or more carbocyclic fused saturated, partially unsaturated, or aromatic rings (usually benz rings) is within the definition of heterocyclyl so long as the system also contains at least one fused ring which contains at least one of the aforementioned heteroatoms. As a substituent, such heterocyclyls may be attached to the remainder of the molecule from either a carbocyclic (e.g., benz) ring or from a heterocyclic ring.
Reference to Z containing "one or more rings" is intended to mean any (single or fused) cyclic moiety or moieties contained in Z. The rings may be carbocyclic or heterocyclic, saturated or partially unsaturated, and aromatic or non-aromatic.
Reference to a fused polycyclic ring system or radical means that all rings in the system are fused.
Reference to "halo" in this specification is inclusive of fluoro, chloro, bromo, and iodo unless noted otherwise.
Reference to an "aryl" substitutent (e.g. (C 6 -C 10 )aryl) means the ring or substitutent is carbocyclic. Aromatic moieties which contain 1 or more heteroatoms are included as a subset of the term "heterocyclyl", as discussed above.
Reference to an "acyl" substituent refers to an alphatic or cyclic hydrocarbon moiety attached to a carbonyl group through which the substituent bonds.
Reference to "alkyl" and "alkoxy" include both straight and branched chain radicals, but it is to be understood that references to individual radicals such as "propyl" or "propoxy" embrace only the straight chain ("normal") radical, branched chain isomers such as "isopropyl" or "isopropoxy" being referred to specifically.
The central benz-heterocyclic ring system of formula I, i.e., the fused bicyclic ring system attached through its single ring nitrogen to --XYZ, is referred to herein as a "1,2,3,4-tetrahydroisoquinoline" for convenience, and this is the convention used most frequently when naming compounds according to the invention as 2-substituted 1,2,3,4-tetrahydroisoquinolin-6-yl amides. It is noted that less frequently, when named as a substituent in a compound, this central ring system is also denoted as a 6-substituted "3,4,-dihydro-1H-isoqulnolin-2-yl" moiety.
A subgroup of compounds of formula I as defined above includes those wherein:
X is CH 2 , CO, or SO 2 ;
Y is selected from:
a direct link, NH,
(C 1 -C 10 )alkyiene and (C 2 -C 10 )alkenylene, either of which may be substituted with phenyl,
provided that X is CH 2 , Y is a direct link,
Z is selected from the following groups:
(1) H,
(2) (C 1 -C 10 )alkoxy, (C 1 -C 10 )alkylthio,
(3) (C 1 -C 10 )alkylamino, di(C 1 -C 10 )alkylamino, (C 6- C 10 )aryl(C 1 -C 10 )alkylamino, provided that Y is not NH,
(4) unsubstituted vinyl, (C 6 -C 10 )aryl, (C 3 -C 8 )cycloalkyl, (C 4 -C 8 )cycloalkenyl,
(5) (C 6 -C 10 )aryloxy,
(6) heterocyclyl selected from the group consisting of five- and six-membered heterocyclic radicals, which may be saturated, partially unsaturated, or aromatic, and the fused benz derivatives thereof, wherein said radicals may contain a total of from 1 to 3 ring heteroatoms independently selected from oxygen, nitrogen, and sulfur,
provided that if X is CH 2 , Z is selected from groups (4) and (6)
wherein, when Z contains one or more rings, said rings may each independently bear 0 to 3 substituents independently selected from halo, hydroxy, nitro, (C 1 -C 8 )alkyl, (C 1 -C 6 )alkoxy; di(C 1 -C 6 )alkylaminocarbonyl, (C 1 -C 3 )perfluoroalkoxy, (C 1 -C 10 )acyl, and (C 1 -C 10 )acyloxy,
and pharmaceutically acceptable salts thereof.
A more particular subgroup includes those compounds within the above subgroup wherein X is methylene, Y is a direct link, and Z is selected from (C 6 -C 10 )aryl, (C 3 -C 8 )cycloalkyl, and (C 4 -C 8 )cycloalkenyl each of which may bear 0 to 3 of the independent substituents noted for Z in the above subgroup, unsubstituted vinyl, and pharmaceutically acceptable salts thereof. Specific values for each include the illustrative values for each given hereinafter.
Another more particular subgroup includes those compounds within the above subgroup wherein X is methylene or CO, Y is a direct link, and Z is heterocyclyl selected from thiophenyl, pyrrolidinyl, pyrrolyl, furanyl, thiazolyl, isoxazolyl, imidazolyl, 1,2,4-triazolyl, pyridyl, pyrimidinyl, and the fused bicyclic (ortho) benz derivatives thereof, including benzimidazolyl, benzthiazolyl, indolyl, isoindolyl, benzofuranyl, benzothiophenyl, benzthiazolyl, quinolinyl, isoquinolinyl, and quinazolinyl, each of which may bear 0 to 3 of the independent substituents noted for Z in the above subgroup, and pharmaceutically acceptable salts thereof.
Specific values for Z as heterocyclyl which may bear 0-3 independent substituents noted for Z in the above subgroup include 2-, and 3-thiophenyl; 2- and 3-benzo b!thiophenyl: 1-, 2- and 4-imidazolyl; 2-benzimidazolyl; 2-, 4-, and 5-thiazolyl; 2-benzothiazolyl; 3-, 4-, and 5-isoxazolyl; 2-quinoxalinyl; 1-, 2-, and 3-pyrrolidinyl; 2-, 3-, and 4-pyridyl; 2- and 4-pyrimidinyl; 2-, 3-, and 4-quinolinyl; 1-, 3-, and 4-isoquinoline; 1-, 2-, and 3-indolyl; 1-, 2-, and 3-isoindolyl; 2- and 3-tetrahydrofuranyl; 1-, 2-, and 3-pyrrolyl; 2- and 3-furanyl; 2- and 3-benzo b!furanyl; 1-, 3-, and 4-pyrazolyl; and 1,2,4-triazolyl-3-yl.
A preferred group of compounds includes those compounds wherein
X is CH 2 or CO;
Y is a direct link;
Z is
H, unsubstituted vinyl, phenyl,
imidazolyl, thiazolyl, thiophenyl, 1,2,4triazolyi, pyridinyl, and pyrimidinyl each of which may bear 0 to 3 of the independent substituents previously noted for the above subgroup;
and pharmaceutically acceptable salts thereof. Specific values of Z (as heterocycyl) for this preferred group include the corresponding specific values noted above.
Within the above preferred group, a subgroup includes those compounds wherein X is CO.
Within the above preferred group, a second subgroup includes those compounds wherein X is CH 2 .
The invention further provides a pharmaceutical composition suitable for the treatment of conditions including atherosclerosis, pancreatits, obesity, hypercholesterolemia, hypertriglyceridemia, hyperlipidemia, and diabetes, comprising a compound of formula I as hereinbefore defined, and a pharmaceutically acceptable carrier.
The compounds of this invention inhibit or decrease apo B secretion, likely by the inhibition of MTP, although it may be possible that other mechanisms are involved as well. The compounds are useful in any of the diseases or conditions in which apo B, serum cholesterol, and/or triglyceride levels are elevated. Accordingly, the invention further provides a method of treating a condition selected from atherosclerosis, pancreatitis, obesity, hypercholesteremia, hypertriglyceridemia, hyperlipidemia, and diabetes, comprising administering to a mammal, especially a human, in need of such treatment an amount of a compound of formula I as defined above sufficient to decrease the secretion of apolipoprotein B. A subgroup of the preceding conditions includes atherosclerosis, obesity, pancreatitis, and diabetes. A more particular subgroup includes atherosclerosis.
The term "treating" as used herein includes preventative as well as disease remitative treatment.
The invention further provides a method of decreasing apo B secretion in a mammal, especially a human, comprising administering to said mammal an apo B-(secretion) decreasing amount of a compound of formula I as defined above.
Certain intermediates are additionally provided as a further feature of the invention:
4'-trifluoromethyl-biphenyl-2-carboxylic acid(1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide,
4'-triuoromethyl-biphenyl-2-carboxylic acid- 3-(2-hydro-ethyl)-4-hydroxylmethyl-phenyl!-amide,
2-(2-hydroxymethyl-5-nitro-phenyl)-ethanol,
6-nitro-3,4-dihydro-1H-isoquinoline-2-arboxylic acid tert-butyl ester,
6amino-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester, and
2-(5-amino-2-hydroxymethyl-phenyl)-ethanol.
It will be appreciated by those skilled in the art that certain compounds of formula I contain an asymmetrically substituted carbon atom and accordingly may exist in, and be isolated in, optically-active and racemic forms. Some compounds may exhibit polymorphism. It is to be understood that the present invention encompasses any racemic, optically-active, polymorphic or stereoisomeric form, or mixtures thereof, which form possesses properties useful in the treatment of atherosclerosis, obesity, and the other conditions noted herein, it being well known in the art how to prepare optically-active forms (for example, by resolution of the racemic form by recrystallization techniques, by synthesis from optically-active starting materials, by chiral synthesis, or by chromatographic separation using a chiral stationary phase) and how to determine efficacy for the treatment of the conditions noted herein by the standard tests described hereinafter.
The chemist of ordinary skill will recognize that certain combinations of substituents or moieties listed in this invention define compounds which will be less stable under physiological conditions (e.g., those containing aminal or acetal linkages). Accordingly, such compounds are less preferred.
An "aliphatic hydrocarbylene radical" for purposes of this invention means a divalent open-chain organic radical containing carbon and hydrogen only. The radical serves as a linking group, denoted above as Y. The radical may be straight chain or branched and/or saturated or unsaturated, containing up to three unsaturated bonds, either double, triple or a mixture of double and triple. The two valences may be on different carbon atoms or on the same carbon atom, and thus the term "alkylidene" is subsumed under this definition. The radical will typically be classified as a (C 1 -C 20 )alkylene radical, a (C 2 -C 20 )alkenylene radical, or a (C 2 -C 20 )alkynylene radical. Typically the radical will contain 1-10 carbon atoms, although longer chains are certainly feasible and within the scope of this invention, as demonstrated in the Examples.
Alkylene radicals include those saturated hydrocarbon groups having 1-20, preferably 1-10 carbon atoms, desived by removing two hydrogen atom from a corresponding saturated acyclic hydrocarbon. Illustrative values having 1-10 carbon atoms include straight chain radicals having the formula (CH 2 ) n wherein n is 1 to 10, such as methylene, dimetnylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, heptamethylene, octamethylene, nonamethylene and so forth. Also included are alkylidene radicals such as ethylidene, propylidene, butylidene, and sec-butylidene. Also included are branched isomers such as 1,1-dimethyidimethylene, 1,1-dimethyltetramethylene, 2,2-dimethytrimethylene and 3,3-dimethylpentamethylene.
Alkenylene radicals include those straight or branched chain radicals having 2-20 carbon atoms, preferably 2-10 carbon atoms, derived by removal of two hydrogen atoms from a corresponding acyclic hydrocarbon group containing at least one double bond. Illustrative values for alkenylene radicals having one double bond include ethenylene (vinylene), propenylene, 1-butenylene, 2-butenylene, and isobutenylene. Alkenylene radicals containing two double bonds (sometimes referred to in the art as alkadienylene radicals) include 3-methyl-2,6heptadienylene, 2-methyl-2,4-heptadienylene,2,8-nonadienylene,3-methyl-2,6-octadienylene,and2,6-decadienylene. An illustrative value for an alkylene radical containing three double bonds (an alkatrienylene radical) is 9,11,13-heptadecatrienylene.
Alkynylene radicals include those straight or branched chain radicals having 2-20 carbon atoms, preferably 2-10 carbon atoms, derived by removal of two hydrogen atoms from a corresponding acyclic hydrocarbon group containing at least one triple bond. Illustrative values include ethynylene, propynylene, 1-butynylene, 1-pentynylene, 1-hexynylene, 2-butynylene, 2-pentynylene, 3,3-dimethyl-1-butynylene, and so forth.
Following are illustrative values for other moieties and substituents named above, which are not to be taken as limiting. It is noted that throughout the specification, if a cyclic or polycyclic radical which can be bonded through different ring atoms is referred to without noting a specific point of attachment, all possible points are intended, whether through a carbon atom or a trivalent nitrogen. As examples, reference to (unsubstituLed) "naphthyl" means naphth-1-yl and naphth2-yl; reference to "pyridyl" means 2-, 3-, or 4-pyridyl; reference to "indolyl" means attachment or bonding through any of the 1-, 2-, 3-, 4-, 5-, 6-, or 7- positions.
Illustrative values for (C 1 -C 10 )alkoxy include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentoxy, hexoxy, heptoxy, and so forth.
Illustrative values for (C 1 -C 10 )alkylthio include the corresponding sulfur-containing compounds of (C 1 -C 10 )alkoxy listed above, including methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, pentylthio, hexylthio, heptylthio, and so forth.
Illustrative values for (C 1 -C 10 )acyl include values for (C 1 -C 10 )alkanoyl such as formyl, acetyl, propionyl, butyryl, and isobutyryl. Also included are other common cycle-containing radicals such as benzoyl.
Illustrative values for (C 1 -C 10 )acyloxy include values for (C 1 -C 10 )alkanoyloxy such as formyloxy, acetyloxy, propionyloxy, butyryloxy, and isobutyryloxy. Also included are other common cycle-containing radicals such as benzoyloxy.
Illustrative values for (C 1 -C 10 )alkoxycarbonyl include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, and isobutoxycarbonyl.
Illustrative values for (C 1 -C 10 )alkylamino include methylamino, ethylamino, propylamino, isopropylamino, butylamino, and isobutylamino.
Illustrative values for di-(C 1 -C 10 )alkylamino include dimethylamino, diethylamino, dipropylamino, dibutylamino, and diisobutylamino.
Illustrative values for (C 6 -C 10 )aryl(C 1 -C 10 )alkylamino are benzylamino, (1-phenylethyl)amino, and (2-phenylethyl)amino;
Illustrative values for (C 6 -C 10 )aryl include phenyl and naphthyl.
Illustrative values of (C 3 -C 8 )cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl.
Illustrative values for fused benz derivatives of (C 3 -C 8 )cycloalkyl include 1,2,3,4-tetrahydronaphthalenyl, indanyl, and fluorenyl.
Illustrative values of polycycloalkyl include adamantyl and 2-bicyclo 2.2.1!heptyl.
Illustrative values for (C 4 -C 8 )cycloalkenyl include cyclobutenyl, cyclopentyenyl, cyclohexenyl, and cycloheptenyl.
Illustrative values for polycycloalkenyl include bicyclo 3.1.1!hept-2-enyl.
Illustrative values for (C 6 -C 10 )aryloxy include phenoxy and naphthyloxy.
Illustrative values for (C 6 -C 10 )arylthio include phenythio and naphthylthio.
Illustrative values for (C 6 -C 10 )aryl(C 1 -C 10 )alkoxy include benzyloxy and phenylethoxy.
Illustrative values for (C 6 -C 10 )aryl(C 1 -C 10 )alkyithio include benzylthio and phenylethylthio.
Illustrative values for (C 3 -C 8 )cycloalkyloxy include cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, and cycloheptyloxy.
Illustrative values for (C 4 -C 8 )cycloalkenyloxy include cyclobutenyloxy, cyclopentenyloxy, cyclohexenyloxy, and cycloheptenyloxy.
Illustrative values for heterocyclyl substituents which are five-member monocyclic radicals include furanyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, 1,2,3-triazolyl, 1,2,4-traizolyl, and 1,3,4thiadiazolyl, and the like.
Illustrative values for heterocyclyl substituents which are six-membered monocyclic radicals include 2H- and 4H-pyranyl, pyridyl, piperidinyl, piperazinyl, pyridazinyl, pyrimidinyl, pyrazinyl, morpholinyl, thiomorpholinyl, 1,3,5-triazinyl, and the like.
Illustrative values for heterocyclyl substituerts which are fused benz derivatives of five-membered heterocyclic radicals include indolyl, isoindolyl, indolinyl, benzofuranyl, benzothiophenyl, benzimidazolyl, benzthiazolyl, and carbazolyl.
Illustrative values for heterocyclyl substituents which are fused benz derivatives of six-membered heterocyclic radicals include quinolinyl, isoquinolinyl, quinazolinyl, phthalazinyl, phenothiazinyl, acridinyl, and phenoxazinyl.
Illustrative examples for heterocyclyl groups which are fused polycyclic radicals other than the fused benz systems exemplified above include purinyl and pteridinyl.
Illustrative values of (C 1 -C 10 )alkyl include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, tertbutyl, pentyl, hexyl, and the like.
Illustrative values for (C 1 -C 3 )perfluoroalkyl include trifluoromethyl, pentafluoroethyl, and heptafluoropropyl.
Illustrative values for (C 1 -C 3 )perfluoroalkoxy include trifluoromethoxy and pentafluoroethoxy.
Compounds according to the invention can frequently be categorized into groups based on the linking group formed by the ring nitrogen of the 1,2,3,4-tetrahydroisoquinoline ring (shown in formula I) taken together with the group in -XYZ which links the XYZ moiety to the said ring nitrogen. Such categories include ##STR3##
Referring to the above linking groups as illustrated, for amides and thioamides (X=CO or CS, respectively) Y is preferably a direct link or hydrocarbylene. In these compounds wherein Y is a direct link, bonding is preferably through the carbonyl or thiocarbonyl group to an aliphatic (i.e., open chain) carbon atom in Z. The said aliphatic carbon atom can be part of a chain which contains one or more heteroatoms. Bonding can also preferably be through the carbonyl or thiocarbonyl group to a cyclic carbon atom. By "cyclic carbon atom" is meant a saturated or unsaturated carbon atom contained in a (saturated, partially unsaturated, or aromatic) carbocyclic or heterocyclic ring. For compounds wherein Y is hydrocarbylene, bonding is through the carbonyl or thiocarbonyl group to an aliphatic carbon atom in Y.
For ureas and thioureas wherein X=CO or CS, respectively and Y=NH, bonding is preferably through the (easternmost as shown) amino group to a cyclic carbon atom in Z. For some ureas and thioureas (X=CO, Y=direct bond) the (easternmost) amino nitrogen is part of Z. In this case bonding is preferably through the easternmost amino group to an aliphatic carbon atom in the remaining portion of Z.
For sulfonamides according to the invention X=SO 2 and Y is preferably hydrocarbylene, or a direct link. For sulfonamides wherein Y is hydrocarbylene, bonding is through the sulfonyl group to an aliphatic carbon atom in Y. For sulfonamides wherein Y is a direct link, bonding is preferably through the sulfonyl group to a cyclic carbon atom in Z. For sulfonamides wherein Y is a direct link, bonding can also be to NH which is part of Z, in which case bonding is through X directly to an amino nitrogen in Z.
N-alkyls (X=CH 2 , Y=direct link) preferably bond through the methylene group to a cyclic carbon atom in Z.
For carbamates wherein X=CO and Y=O bonding is preferably through the oxy (O) portion of the linkage to a cyclic carbon atom in the remaining portion of Z. For carbamates wherein X=CO and Y=direct link the oxy linkage is part of Z, and in these bonding is preferably to a cyclic or aliphalic carbon atom In the remaining portion of Z, most preferably to an aliphatic carbon atom in the remaining portion of Z.
For those compounds of formula I wherein Y is hydrocarbylene, bonding to Z is through an aliphatic carbon atom in Y preferably to H or to a cyclic carbon atom or a heteroatom in Z.
When grouping compounds below and in the Examples, it is the above structural categories to which reference is made.
Preferred compounds include the following which, where possible, have been categorized according to the types of linking groups shown in partial structure above.
AMIDES
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-phenyl-acetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-phenoxy-acetyl-1,2,3,4-tetrahydroisoquinotin-6-yl)-amide
4'-Trifluoromethyl-biphenyt2carboxylic acid (2-pentanoyl-1,2,3,4tetrahydroisoquinolin-6-yl)-amide
4'-Trifiuoromethyl-biphenyl-2 carboxylic acid (2-cyclobutane carbonyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
4'-Trifiuoromethyl-biphenyl-2-caboxylic acid 2-(thiophen-2-yl-acetyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-butyryl-1,2,3,4tetrahydrnisoquinolin-6-yl)-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-ethoxy-acetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid {2- (4fluoro-phenyl)-acetyl-!-1,2,3,4-tetrahydroisoquinolin-6-yl}-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-methyl-butyryl)-1,2,3,4-tetrahydroisoquinolin-6yl!-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-but-3-enoyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-methoxy-acetyl-1,2,3,4tetrahydroisoquinolin-6-yl)-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-ethylthio-acetyl-1,2,3,4tetrahydroisoquinolin-6-yl)-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(6diethyl-carbamoyl-cyclohex-3-enecarbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
4'-Trifluoromethyl-biphenyl-2-caboxylic acid 2-(cyclopent-1-enyl-acetyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-hex-3enoyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(tetrahydrofuran-3-carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(thiophen-3-yl-acetyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(pyridine-2-carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
UREAS
6- (4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinoline-2-carboxylic acid phenylamide
6- (4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinoline-2-carboxylic acid hexylamide
6- (4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-di-hydro-1H-isoquinoline-2-carboxylic acid benzylamide
6- (4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinoline-2-carboxylic acid (R)-1-phenyl-ethyl!-amide
6- (4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinoline-2-carboxylic acid pyridin-2-ylamide
SULFONAMIDES
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(propane-2-sufonyl)-1,2,3,4tetrahydroisoquinolin-6-yl!-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-dimethylsulfamoyl-1,2,3,4tetrahydroisoquinolin-6-yl)-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2-trifluoromethoxy-benzenesulfonyl)-1,2,3,4tetrahydroisoquinolin-6-yl!-amide
THIOUREAS
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-cyclopropylthiocarbamoyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
N-ALKYLS
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2,6,6-trimethyl-cyclohex-2-enylmethyl)-1,2,3,4tetrahydroisoquinolin-6-yl!-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2,4-dichloro-benzyl)-1,2,3,4tetrahydroisoquinolin-6-yl!-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1,5a,6,9,9a,9b-hexahydro-4H-dibenzofuran-4a-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-thiophen-2-ylmethyl-1,2,3,4tetrahydroisoquinolin-6-yl)-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1H-pyrrol-2-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-furan-2-ylmethyl-1,2,3,4tetrahydroisoquinolin-6-yl)-amide
Acetic acid 5-{6- (4'-trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinolin-2-ylmethyl}-furan-2-ylmethyl ester
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-thiophen-3-ylmethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2,5-dimethoxy-tetrahydrofuran-3-ylmethyl)-1,2,3,4-tetrahydro-isoquinolin-6-yl!-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-benzyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-pyridin-2-ylmethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-quinolin-2-ylmethyl-1,2,3,4tetrahydroisoquinolin-6-yl)-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-chloro-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-pyrimidin-2-ylmethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-nitro-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1H-imidazol-2-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1-methyl-pyrrol-2-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1H-benzoimidazol-2-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-thiazol-2-ylmethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1-methyl-imidazol-2-ylmethyl)-1,2,3,4-tetrahydro-isoquinolin-6-yl!-amide
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1H- 1,2,4!triazol-3-ylmethyl)-1,2,3,4-tetrahydro-isoquinolin-6-yl!-amide
4-trifluoromethyl-biphenyl-2-carboxylic acid (2-allyl)-1,2,3,4-tetrahydroisoquinoline-6-yl!amide
CARBAMATES
6- (4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester
Particularly preferred compounds include the following:
4-Trifluoromethyl-biphenyl-2-carboxylicacid 2-(thiophen-2-yl-acetyl)-1,2,3,4tetrahydroisoquinolin-6-yl!-amide,
6- (4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinoline-2-carboxylic acid (1-phenyl-ethyl)-amide,
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-pyridin-2-ylmethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide,
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1H-imidazol-2-ylmethyl)-1,2,3,4-tetrahydro-isoquinolin-6-yl!-amide,
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-thiazol-2-ylmethyl-1,2,3,4tetrahydroisoquinolin-6-yl)-amide, and
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1H- 1,2,4!triazol-3-ylmethyl)-1,2,3,4-tetrahydro-isoquinolin-6-yl!-amide,
DETAILED DESCRIPTION
In the discussion which follows, common chemical abbreviations and acronyms have been employed: Me (methyl); Et (ethyl); THF (tetrahydrofuran); BOC (tertbutyloxycarbonyl, a blocking group); Ms (methanesulfonyl, mesyl); TFA (trifluoroacetic acid); Ac (Acetyl); RP (reverse phase); HPLC (high performance liquid chromatography);
Compounds of formula I can be made by processes which include processes known in the chemical arts for the production of similar compounds. Such processes for the manufacture of a compound of formula I as defined above are provided as further features of the invention and are illustrated by the following procedures in which the meanings of generic radicals are as given above unless otherwise qualified. The processes involve treating a compound of formula II, ##STR4## which contributes the western portion of the molecule (i.e., the moiety consisting of formula II with the hydrogen removed from the tetrahydroisoquinolinyl ring nitrogen) with a reactant which adds the eastern (XYZ) moiety. Reactants which furnish the eastern moiety are generally commercially available or well precedented in the scientific literature. The compound of formula II is 4'-trifluoromethylbiphenyl-2-carboxylic acid (1,2,3,4-tetrahydroisoquinolin-6-yl)amide and is referred to herein simply as "compound II" for the sake of convenience. The western portion of the molecule it contributes to compounds according to the invention is the 6- (4'-trifluoromethyl)biphen-2-ylcarbonylamino!-3,4-dihydro-1H-isoquinolin-2-yl moiety.
The processes can be effected, generally:
(a) for a compound of formula I wherein X is carbonyl, by treating compound II with a carboxylic acid of formula Z--Y--COOH in the presence of a coupling reagent. The coupling reagent is typically a carbodiimide, preferably 1-ethyl-(3-dimethylaminopropyl)carbodiimide which is known by the acronym EDC and can be obtained commercially. The EDC can advantageously be polymer bound as disclosed in U.S. Pat. No. 5,416,193. The reaction is typically conducted at room temperature and in an inert solvent, although heating can be employed if desired. Typical reaction spans vary anywhere from a few minutes to 48 hours, typically overnight.
(b) for a compound of formula I wherein X is carbonyl or thiocarbonyl, by treating compound II with an activated form of a corresponding carboxylic acid or thiocarboxylic acid, in the presence of a base. Typically the activated form is the corresponding acid chloride of formula Z--Y--COCl or Z--Y--CSCl, respectively. The base is, for example, an amine which may advantageously be bound to a polymer to reduce cleanup, a typical bound base being polymer bound morpholinomethyl-polystyrene. The reaction is generally conducted at room temperature with stirring, shaking or other form of agitation for a time necessary to allow the reaction to proceed to a reasonable degree if not to completion, typically 2-48 hours, typically overnight.
Compounds made as disclosed in (a) and (b) above form structural types previously referred to as amides and thioamides.
(c) for a compound of formula I wherein X is carbonyl or thiocarbonyl and Y is NH, by treating compound II with, respectively, a corresponding isocyanate of formula Z--N=C=O orthioisocyanate of formula Z--N=C=S, respectively. The resulting products are compounds according to the invention referred to herein by structural type as ureas and thioureas, respectively. The reaction is generally conducted in an inert solvent, typically a halogenated hydrocarbon such as 1,2-dichloroethane, typically for a time of 2-48 hours, usually overnight.
(d) for a compound of formula I wherein X is sulfonyl, by treating compound II with a corresponding sulfonyl chloride of formula Z--Y--SO 2 Cl. The resulting product is of the sulfonamide structural type. The reaction is typically conducted in an inert solvent such as a halogenated hydrocarbon (e.g., 1,2-dichloroethane), at room temperature for several hours or more, typically overnight.
(e) for a compound of formula I wherein X is CH 2 and Y is a direct link, by treating compound II with an aldehyde of formula Z--CHO in the presence of sodium triacetoxyborohydride. This is essentially the reductive amination reported in Abdel-Magid et al., Tetrahedron Lett., 31(39), 5595-5598 (1990). The resulting product is of the N-alkyl structural type. The reaction is conducted in an appropriate solvent such as a halogenated hydrocarbon, with shaking or agitating otherwise for a time of from a few hours to several days at room temperature, although heat can be applied to increase reaction rate if desired.
(f) for a compound of formula I wherein X is CH 2 and Y is a direct link, by treating a compound of the formula ##STR5## with a corresponding compound of the formula Z--CH 2 --NH 2 , in the presence of mesyl chloride, typically two equivalents.
(g) for a compound of formula I wherein X is thiocarbonyl by treating a corresponding compound of formula I wherein X is CO with phosphorus pentasulfide, P 4 S 10 . The reaction can be carried out conventionally by using a stoichiometric amount of P 4 S 10 (or an excess if desired) and heating it together with the corresponding amide in an inert solvent such as pyridine, xylene, benzene, chlorobenzene or toluene. The reaction is usually implemented at reflux for anywhere from a few minutes to a few hours.
The compound of formula II can be made as outlined in Scheme I and as specifically exemplified in Example 1. Referring to Scheme I, 2-(4-bromophenyl)ethylamine hydrobromide is reacted with ethyl formate in the presence of a base to make N- 2-(4-bromophenyl)ethyl!formamide. The fornamide is then treated with phosphorus pentoxide in polyphosphoric acid to cyclize, followed by treatment with hydrogen halide (e.g., HCl) gas to form the hydrohalide salt of 7-bromo-3,4-dihydroisoquinoline hydrohalide. The hydrohalide salt is then reduced to afford 7-bromo-1,2,3,4-tetrahydroisoquinoline. The reduced material is then nitrated by treatment with potassium nitrate in concentrated sulfuric acid and the appropriate fraction separated to yield 7-bromo6-nitro-1,2,3,4-tetrahydroisoquinoline. The nitrated material is then reacted with di-tert-butyl dicarbonate in the presence of a base to block the ring tetrahydroisoquinoline nitrogen, thereby affording 7-bromo-6-nitro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester. The ester is then hydrogenated in the presence of palladium-on-calcium carbonate to form the corresponding 6-amino-3,4-dihydro-1H-isoquinoline-2-carboxylic acid ester. The amine is then reacted with 4'-trifluoromethylbiphenyl-2-carboxylic acid to form 6- 4'-trifluoromethylbiphenyl-2-carbonyl)amino!3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester. This product can then be deblocked conventionally to make compound II, 4'-trifluoromethylbiphenyl-2-carboxylic acid (1,2,3,4tetrahydroisoquinolin-6-yl)amide. ##STR6##
The compound of formula II can, alternatively, be made by a second route as illustrated in Scheme 2. Referring to Scheme 2, nitrobenzoic acid (1) can be treated with dimethyl malonate in the presence of base to form compound (2). Compound (2) can then be treated with aqueous alcoholic base to effect hydrolysis and decarboxylation to yield compound (3). Compound (3) can, if desired, be treated with acetic anhydride in toluene or other hydrocarbon solvent to make anhydride (3a). Reduction of compound (3) or (3a) affords the corresponding diol (4) which can then be treated with mesyl chloride to form the dimesylate which is subsequently cyclized with ammonia, thereby affording compound (5). Compound (5) is then conventionally N-blocked to yield compound (6), which in turn is reduced to make corresponding amine (7). Amine (7) can then be treated with the acid chloride of 4'-trifluoromethylbiphenyl-2-carboxylic acid (made by treating the corresponding free acid with thionyl chloride) to make the corresponding amide analog (8) of compound II. Compound (8) can be deblocked conventionally, as illustrated and discussed in Scheme I, to afford compound II. ##STR7##
The compound of formula III can be made as illustrated in Scheme 3 starting with the diol (4) first shown in Scheme 2. Referring to Scheme (3), diol (4) is reduced with hydrogen in the presence of platinum-on-carbon catalyst to make corresponding amino diol (9). Amino diol (9) can then be reacted with the acid chloride of 4'-trifluoromethylbiphenyl-2-carboxylic acid to afford compound III. Compound III can, as shown, then be cyclized with ammonia in the presence of a catalyst to make compound II.
As also shown in Scheme 3, compound III can also be reacted directly with a corresponding amine of formula Z--CH 2 --NH 2 in the presence of base and catalyst to make a compound of formula I, designated Ia in Scheme 3, wherein X is CH 2 and Y is a direct link. ##STR8##
Conventional methods and/or techniques of purification and separation known to those skilled in the art can be used to isolate the compounds of this invention. Such techniques include all types of chromatography (HPLC, column chromatography using common adsorbents such as silica gel, and thin layer chromatography), recrystallization, and differential (i.e., liquid-iquid) extraction techniques.
The compounds herein form cationic salts such as acid addition salts and the expression "pharmaceutically-acceptable safts" is intended to define but not be limited to such salts as the hydrochloride, hydrobromide, sulfate, hydrogen sulfate, phosphate, hydrogen phosphate, dihydrogenphosphate, acetate, succinate, citrate, methanesulfonate (mesylate) and p-toluenesulfonate (tosylate) salts. For many compounds polyaddition salts are feasible.
The acid addition salts of the compounds of the present invention are readily prepared by reacting the base forms with the appropriate acid. When the salt is of a monobasic acid (e.g., the hydrochloride, the hydrobromide, the p-toluenesulfonate, the acetate), the hydrogen form of a dibasic acid (e.g., the hydrogen sulfate, the succinate) or the dihydrogen form of a tribasic acid (e.g., the dihydrogen phosphate, the citrate), at least one molar equivalent and usually a molar excess of the acid is employed. However when such salts as the sulfate, the hemisuccinate, the hydrogen phosphate or the phosphate are desired, the appropriate and exact chemical equivalents of acid will generally be used. The free base and the acid are usually combined in a co-solvent from which the desired salt precipitates, or can be otherwise isolated by concentration and/or addition of a non-solvent.
The compounds of the present invention are orally administrable and are accordingly used in combination with a pharmaceutically acceptable carrier or diluent suitable to oral dosage forms. Suitable pharmaceutically-acceptable carriers include inert solid fillers or diluents and sterile aqueous or organic solutions. The active compound will be present in such pharmaceutical compositions in amounts sufficient to provide the desired dosage amount in the range described below. Thus, for oral administration the compounds can be combined with a suitable solid or liquid carrier or diluent to form capsules, tablets, powders, syrups, solutions, suspensions and the like. The pharmaceutical compositions may, if desired, contain additional components such as flavorants, sweeteners, excipients and the like.
The tablets, pills, capsules, and the like may also contain a binder such as gum tragacanth, acacia, corn starch or gelatin; excipients such as dicalcium phosphate; a disintegrating agent such as corn starch, potato starch, alginic acid; a lubricant such as magnesium stearate; and a sweetening agent such as sucrose, lactose or saccharin. When a dosage unit form is a capsule, it may contain, in addition to materials of the above type, a liquid carrier such as a fatty oil.
Various other materials may be present as coatings or to modify the physical form of the dosage unit. For instance, tablets may be coated with shellac, sugar or both. A syrup or elixir may contain, in addition to the active ingredient, sucrose as a sweetening agent, methyl and propylparabens as preservatives, a dye and a flavoring such as cherry or orange flavor.
These active compounds may also be administered parenterally. For parenteral administration the compounds can be combined with sterile aqueous or organic media to form injectable solutions or suspensions. Solutions or suspensions of these active compounds can be prepared in water suitably mixed with a surfactant such as hydroxypropylcellulose. Dispersions can also be prepared in sesame or peanut oil, ethanol, water, polyol (e.g., glycerol, propylene glycol and liquid polyethylene glycol), suitable mixtures thereof, vegetable oils, N-methyl glucamine, polyvinylpyrrolidone and mixtures thereof in oils as well as aqueous solutions of water-soluble pharmaceutically acceptable salts of the compounds. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms. The injectable solutions prepared in this manner can then be administered intravenously, intraperitoneally, subcutaneously, or intramuscularly.
The pharmaceutical forms suitable for injectable use include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In all cases, the form must be sterile and must be fluid to the extent that easy syingability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi.
The dose of a compound of formula I which is administered will generally be varied according to principles well known in the art taking into account the severity of the condition being treated and the route of administration. In general, a compound of formula I will be administered to a warm blooded animal (such as a human) so that an effective dose, usually a daily dose administered in unitary or divided portions, is received, for example a dose in the range of about 0.1 to about 15 mg/kg body weight, preferably about 1 to about 5 mg/kg body weight. The total daily dose received will generally be between 1 and 1000 mg, preferably between 5 and 350 mg.
The compounds of this invention may be used in conjunction with other pharmaceutical agents, including other lipid lowering agents. Such agents include cholesterol biosynthesis inhibitors, especially HMG CoA reductase inhibitors and squalene synthetase inhibitors; bile acid sequestrants; fibrates; cholesterol absorption inhibitors; and niacin.
A test compound is considered to be active if it is active in any of the following screens.
The activity of a compound according to the invention can be assessed by measuring inhibition of apo B secretion in HepG2 cells.
HepG2 cells are grown in Dulbecco's Modified Eagles Medium plus 10% fetal bovine serum (growth medium; Gibco) in. 96well culture plates in a humidified atmosphere containing 5% carbon dioxide until they are approximately 70% confluent. Test compounds are dissolved at 10-20 mM in dimethyl sulfoxide which is then diluted to 1 μM in growth medium. Serial 1:1 dilutions of this stock are made in growth medium and 100 μl of each are added to separate wells of a 96-well culture plates containing HepG2 cells. Twenty four hours later, growth medium is collected and assayed by specific ELISA for apoB and, as a control, apoAl concentrations. Inhibitors are identified as compounds that decrease apoB secretion into the medium without affecting the secretion of apoAl. The ELISA for apoB is performed as follows. Monoclonal antibody against human apoB (Chemicon) is diluted to 5 μg/ml in phosphate buffered saline/azide (PBS+0.02% Na azide) and 100 μl are added to each well of a 96-well plate (NUNC Maxisorb). After an overnight incubation at room temperature, the antibody solution is removed and wells are washed 3 times with PBS/azide. Non-specific sites on the plastic are blocked by incubating wells for 1-3 hours in a solution of 1% (w/v) bovine serum albumin (BSA) made in PBS/azide. 100 μl of various dilutions of growth medium from the HepG2 cells or apoB standards (made in 0.04% Tween 20/1% BSA in PBS/azide) added to each well and incubated for 18 hours. Wells are aspirated and washed 3 times (0.1% Tween 20 in PBS) prior to adding 100 μl of a 1/1000 dilution of the secondary antibody, goat anti-human apoB (Chemicon). After a 3 hr incubation at room temperature, this solution is aspirated and the wells are again washed 3 times as above. 100 μl of a 1:1600 dilution (in PBS/1% BSA/2mM MgCl 2 ) of rabbit anti-goat IgG conjugated to alkaline phosphatase (Sigma) are then added to each well and incubated for 1 hr at room temperature. After aspirating, the wells are washed 4 times as above and 100 μl of 1 mg/ml p-nitrophenylphosphate (pNPP; Sigma) in 25 mM sodium (bi)carbonate/2 mM MgCl 2 , pH 9.5, are added to each well and incubated for 20-30 minutes and then the reaction is terminated by the addition of 50 μl of 0.2N NaOH. Absorbance of each well is read at 405 nm and the background at 650 nm is subtracted. ApoB concentration is calculated from a standard curve constructed from purified LDL standards that are run in parallel in the same assay. ApoAl is measured in an analogous manner except that antibodies for apoAl (Chemicon) are used in place of the antibodies for apoB and antigen incubation is at 37° instead of room temperature.
Activity can also be confirmed if a test compound inhibits MTP activity directly.
Inhibition of MTP activity by a compound can be quantitated by observing the inhibition of transfer of radiolabeled triglyceride from donor vesicles to acceptor vesicles in the presence of soluble human MTP. The procedure for preparing MTP is based on the method of Wetterau and Zilversmit (Biochem. Biophys. Acta (1986) 875:610). Briefly, human liver chunks, frozen at -80° C., are thawed on ice, minced, and rinsed several times with ice cold 0.25M sucrose. All subsequent steps are performed on ice. A 50% homogenate in 0.25M sucrose is prepared using a Potter-Elvehjem Teflon pestle. The homogenate is diluted 1:1 with 0.25M sucrose and centrifuged at 10,000×g for 20 min at 4° C. The pellet is resuspended in sucrose and recentrifuged at 10,000×g for 20 min. The supematants are combined and the microsomes pelleted by centrifugation at 105,000×g for 75 min. The supematant is discarded and the microsomal pellet is suspended in a minimal volume of 0.25M sucrose, diluted to 3 ml per gm starting liver weight with 0.15M Tris-HCl pH 8.0. This suspension is divided into 12 fractions, and centrifuged at 105,000×g for 75 min. The supernatants are discarded and the microsomal pellets are stored frozen at -80° C. until needed. For preparation of MTP prior to performing the assay, a thawed pellet is suspended in 12 ml of cold 50 mM Tris-HCl, 50 mM KCl, 5 mM MgCl, pH 7.4 and 1.2 ml of a 0.54% deoxycholate (pH 7.4) solution is added slowiy with mixing to disrupt the microsomal membrane. After a 30 min incubation on ice with gentle mixing, the suspension is centrifuged at 105,000×g for 75 min. The supematant, containing the soluble MTP protein, is dialyzed for 2-3 days with 4 changes of assay buffer (150 mM Tris-HCl, 40 mM NaCl, mM EDTA, 0.02% NaN3, pH 7.4). The human liver MTP is stored at 4° C. and diluted 1:5 with assay buffer just before use. MTP preparations show no notable loss of transfer activity with storage up to 30 days.
Liposomes are prepared under nitrogen by room temperature, bath sonication of a dispersion of 400μM egg phosphatidylcholine (PC), 75μM bovine heart cardiolipin, and 0.82 μM 14C!-triolein (110 Cl/mol) in assay buffer. The lipids in chloroform are added in the proper amounts and dried under a nitrogen stream before hydrating with assay buffer. Acceptor liposomes are prepared under nitrogen by room temperature bath sonication of a dispersion of 1.2 mM PC, 2.3 μM triolein and 30 pM 3H!-PC (50 Ci/mol) in assay buffer. The donor and acceptor liposomes are centrifuged at 160,000×g for 2 hrs at 7° C. The top 80% of the supernatant, containing small unilamellar liposomes, are carefully removed and stored at 4° C. until used for transfer assays.
MTP activity is measured using a transfer assay which is initiated by mixing donor and acceptor vesicles together with the soluble MTP and test compound. To 100 μl of either a 5% BSA (control) or 5% BSA containing the test compound, are added 500 μlassay buffer, 100 μl donor liposomes, 200 μl acceptor liposomes and 100 μl of diluted MTP protein. After incubation at 37° C. for 45 min., triglyceride transfer is terminated by adding 500 μl of a 50% (w/v) DEAE cellulose suspension in assay buffer. Following 4 min of agitation, the donor liposomes, bound to the DEAE cellulose, are selectively sedimented by low speed centrifugation. An aliquot of the supernatant containing the acceptor liposomes is counted and the 3H and 14C counts are used to calculate the percent recovery of acceptor liposomes and the percent triglyceride transfer using first order kinetics. Inhibition of triglyceride transfer by test compound is manifest as a decrease in 14C radioactivity compared to controls where no test compound is present.
Actity of test compounds as MTP inhibitors can also be measured in vivo according to the following test.
Male mice (20-39 g.; various strains) are dosed by oral gavage (0.25-ml/25 g. body weight) with test compound suspended in an aqueous 0.5% methyl cellulose solution. Compound solutions are dosed either multiple times over several days or, alternatively, once 90 minutes before mice are euthanized and blood is collected for preparation of serum. The serum is assayed for triglyceride concentration by a commercial enzymatic assay (Triglyceride G: Wako Fine Chemicals). MTP inhibitors are identified by their ability to lower serum triglycerides as compared to control mice dosed with vehicle.
The present invention is illustrated by the following Examples. However, it should be understood that the invention is not limited to the specific details of these examples.
EXAMPLE 1
This example illustrates how to make the intermediate compound of formula II N- 2-(4-Bromo-phenyl)-ethyl!-formamide
500 g (1.78 mol) of 2-(4-bromo-phenyl)-ethylamine hydrobromide, 1 liter (12.4 mol) of ethyl formate and 248 ml (1.78 mol) of triethylamine were combined and heated to reflux for 3 hrs. The reaction was treated with 1 liter each of deionized water and ethyl acetate. The organic layer was separated and washed with 1 liter each of water and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated to yield 378 g of a solid.
MS (Cl): 245(M+NH 4 + )
7-Bromo-3,4-dihydro-isoquinoline hydrochloride
In a 12 liter three neck round bottom flask, 4 kg of polyphosphoric acid was heated to 150° C. and stirred. To the stirring polyphosphoric acid was added 530 g (3.75 mol) of phosphorus pentoxide in three portions of approximately 176.7 g each. After the phosphorus pentoxide had dissolved, 378 g (1.66 mol) of N- 2-(4bromo-phenyl)-ethyl!-formamide was added. The reaction temperature was then raised to 200° C. and maitained for two hours. At this point, the reaction temperature was allowed to cool to 160° C. and poured onto 16 liters of ice. The mixture was stirred for 0.5 hours, basified to pH 12 with 10N sodium hydroxide solution and extracted three times with 3 liters of dichloromethane. The combined organic layers were washed with 1 liter of saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated to an oil. The oil was dissolved in 2.5 liters of methanol and saturated with anhydrous HCl gas. The resulting solution was concentrated to one liter volume and 1 liter of diethyl ether was added. The resulting precipitate was filtered, washed with diethyl ether and air dried to yield 219 g of a solid.
MS (Cl): 210 (M+H + )
7-Bromo-1,2,3,4-tetrahydroisoquinoline
219 g (0.89 mol) of 7-bromo-3,4-dihydro-isoquinoline hydrochloride and 1.5 liters of water were combined and heated to 50° C. 33.7 g (0.89 mol) of sodium borohydrde was added in portions over 0.5 hours at which time the temperature rose to 62° C. The reaction was then cooled to ambient temperature and extracted three times with 1 liter of dichloromethane. The combined organic layers were washed with 1 liter of saturated sodium chloride solution, dried over anhydrous sodium sulfate and concentrated to yield 173 g of an oil.
MS (Cl): 212 (M+H + )
7-Bromo-6-nitro-1,2,3,4-tetrahydroisoquinoline
In a 5 liter three neck round bottom flask, 173 9 (0.813 mol) of 7-bromo-1,2,3,4-tetrahydroisoquinoline was dissolved carefully into 950 ml of concentrated sulfuric acid. The resulting solution was cooled to -5° C. and a solution of 82.7 g (0.816 mol) of potassium nitrate in 1 liter of concentrated sulfuric acid was added dropwise. After addition, the reaction was maintained at -5° C. for 15 minutes and poured onto 3 liters of ice. The resulting mixture was basffied to pH 14 with 50% sodium hydroxide solution. The basic solution was extracted three times with 1 liter of dichloromethane. The combined organic layers were washed with 1 liter each of water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to yield 201 g of an oil. The oil preadsorbed onto silica gel was charged onto a column of 4 kg of silica gel and eluted with a gradient of 1-5% methanol/dichloromethane. The fractions containing product were combined and concentrated to yield 115 g of a solid.
1 H NMR (300 MHz, CDCl 3 ) δ 7.61 (s, 1H); 7.38 (s, 1H); 4.10 (s, 2H); 3.20 (t, 2H); 2.90 (t, 2H).
7-Bromo-6-nitro-3,4-dihydro-1H-isoquinoline-2-carboxlic acid tert-butyl ester
115 g (0.447 mol) of7-bromo-6-nitro-1,2,3,4-tetrahydroisoquinoline, 45.2 g (0.447 mol) of TEA, 97.5 g (0.447 mol) of di-tert-butyl dicarbonate, 3.2 liter of dioxane and 0.5 liter of water were combined and stirred at ambient temperature for 1.5 hrs. The reaction was concentrated to remove the dioxane, 1 liter of saturated sodium bicarbonate was added and extracted two times with 1 liter of dichloromethane. The organic layer was extracted with brine, dried over magnesium sulfate and concentrated. The resulting solid was recrystallized from isopropanol to yield 118 g of a solid.
1 H NMR (250 MHz, DMSO) δ 7.89 (s, 1H); 7.81 (s, 1H); 4.58 (s, 2H); 3.56 (t, 2H); 2.81 (t, 2H); 1.42 (s, 9H).
6Amino-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester
59 g (0.16 mol) of 7-bromo-6-nitro-3,4-dihydro-1H-isoquinolin-2-carboxylic acid tert-butyl ester, 10 g of 5% palladium on calcium carbonate and 49 g of ammonium acetate in 1 liter of acetic acid was hydrogenated on a Parr shaker for 5 hrs. The reaction was filtered through CELITE®concentrated, basified to pH 12 with 4N sodium hydroxide and extracted with methylene chloride. The organic layer was washed with water, brine, dried over magnesium sulfate and concentrated to yield 40 g of an oil.
1 H NMR (300 MHz, DMSO) δ 4.87 (s, 2H); 4.27 (s, 2H); 3.44 (t, 2H); 2.57 (t, 2H); 1.39 (s, 9H).
6- (4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester
7.6 g (29 mmol) of 4'-trifluoromethyl-biphenyl-2-carboxylic acid, 7.1 g (29 mmol) of 6-amino-3,4-dihydro-1H-isoquinoline-2-caboxyiic acid tert-butyl ester, 100 mg of DMAP and 6.1 g (32 mmol) of EDCl were mixed in 130 ml of methylene chloride for 12 hrs. Reaction was extracted with 2×150 ml 1N HCl, 2×150 ml 1N NaOH, 150 ml water, brine and concentrated to yield 14 g of a beige foam.
MS (Cl): 519 (M+Na + )
1 H NMR (250 MHz, CDCl 3 ) δ 4.49 (s, 2H); 3.60 (t, 2H); 2.77 (t, 2H).
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (1,2,3,4tetrahydroisoquinolin-6-yl)-amide
4 g (8 mmol) of 6- (4'-trifiuoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester and 6 ml (78 mmol) of TFA were mixed in 60 ml of methylene chloride for 5 hrs. 40 ml of methylene chloride was added and organic was extracted with 3×50 ml of saturated sodium bicarbonate and brine. Organic layer was dried over sodium sulfate and concentrated to yield 3.1 gm of solid.
MS (Cl): 397 (M+H + )
The following compounds, classified as amides by the criteria previously set forth, were synthesized by the procedure described in method A.
Method A
Into a glass screw topped vial was placed 150 μl of a 0.020M solution of the acid chloride in 1,2-dichloroethane (3.0 μmol), followed by 83 μl of 0.030M 4'-trifluoromethyl-biphenyl-2-carboxylic acid (1,2,3,4-tetrahydroisoquinolin-6-yl)-amide in 1,2-dichloroethane (2.5 μmol), followed by 25 mg polymer bound morpholinomethylpolystyrene (@2.5 μmol/gm=62 μmol). After shaking at 20° C. for 16 hours, 10 μl was removed and diluted to 100 μl with methanol for RPHPLC and MS analysis. The polymer was removed by filtration and the filtrate was concentrated to dryness under vacuum.
EXAMPLE 2
By Method A described above, 4'-trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-cyclopentyl-propionyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide was made by reacting compound II with 3-cyclopentylpropionyl chloride in the presence of polymer-bound morpholine.
MS (Cl): 521 (M+H + )
EXAMPLES 3-39
The following compounds were made according to methods analogous to those described in Example 2 by reacting compound II with the approprate corresponding acid chloride.
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-phenylacetyl-1,2,3,4-tetrahydrosoquinolin-6-yl)-amide
MS (Cl): 515 (M+H + ); 1 H NMR (250 MHz, CDCl 3 ) δ 4.68 and 4.53 (s, 2H); 3.80 (s, 2H); 3.80 and 3.61 (t, 2H); 2.76 and 2.59 (t, 2H).
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-benzoyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 501 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(furan-2-carbonyl)-1,2,3,4tetrahydrosoquinolin-6-yl!-amide
MS (Cl): 491 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(4-chloro-butyryl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 501 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-benzyloxyacetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 545 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(4-heptyl-benzoyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 599 (M+H + )
4'-Trifluoromethyl-biphenyl-2carboxylic acid 2-(bicyclo 2.2.1!hept-5-ene-2-carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 517 (M+H + )
4'-Trifluoromethylbiphenyl-2-carboxylic acid 2-(5-methyl-5-phenyl-isoxazole-4-carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 582 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylicacid(2-tetradecanoyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 607 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3,3-dimethyl-butyryl)-1,2,3,4-tetraydroisoquinolin-6-yl!-amide
MS (Cl): 495 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-phenoxyacetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 531 (M+H + )
Aceticacid2oxo-1-phenyl-2-{6- (4'-trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinolin-2-yl}-ethyl ester
MS (Cl): 573 (M+H + )
4'-Trifluoromethyl-biphenyl-2carboxylic acid 2-(thiophene-2-carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 507 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2,2,5,7-tetramethyl-1-oxo-indane-4carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 611 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-octanoyl-1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide
MS (Cl): 523 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-octadec-9-enoyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 661 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylicacid 2-(quinoxaline-2-carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 553 (M+H + )
4-Oxo-4-{6- (4'-trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinolin-2-yl}-butyric acid methyl ester
MS (Cl): 511 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(biphenylcarbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 577 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2pentanoyl-1,2,3,4tetrahydro-isoquinolin-6-yl)-amide
MS (Cl): 481 (M+H + )
4'-Trifluormethy-biphenyl-2-carboxylic acid (2-isobutyryl-1,2,3,4tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 467 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-decanoyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 551 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-octadecanoyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 663 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-hexanoyl-1,2,3,4-tetrahydroisoquinolin-6-yl)amide
MS (Cl): 495 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-phenyl-propionyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 529 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-cyclohexanecarbonyl-1,2,3,4-tetrahydroisoquinoin-6-yl)-amide
MS (Cl): 507 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-cyclobutanecarbonyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 479 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2-ethyl-hexanoyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 523 (M+H + )
3-Oxo-3-{6- (4'-trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinolin-2-yl}-propionic acid methyl ester
MS (Cl): 497 (M+H + )
5-Oxo-5-{6- (4'-trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinolin-2-yl}-pentanoic acid methyl ester
MS (Cl): 525 (M+H + )
4'-Trifuoromethyl-biphenyl-2-carboxylic acid 2-(2-chloro-propionyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 487 (M+H + )
5-Oxo-5-{6- (4'-trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinolin-2-yl}-pentanoic acid ethyl ester
MS (Cl): 539 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid {2- (3-methoxyphenyl)-acetyl!-1,2,3,4tetmhydroisoquinolin-6-yl}-amide
MS (Cl): 545 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(thiophen-2-yl-acetyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 521 (M+H + )
1 H NMR (250 MHz, CDCl 3 ) δ 4.68 and 4.60 (s, 2H); 3.97(s, 2H); 3.80 and 3.69 (t, 2H); 2.71 (m, 2H). 4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-butyryl-1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide
MS (Cl): 467 (M+H + )
4-Oxo-4-{6- (4'-trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4dihydro-1H-isoquinolin-2-yl}-butyric acid methyl ester
MS (Cl): 511 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2octadec-11-enoyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 661 (M+H + )
METHOD B
Polymer bound EDC
1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (20 gm, 0.104 mol) was partitioned between 400 ml methylene chloride, 200 ml water, and 100 ml concentrated ammonium hydroxide. The aqueous layer was extracted with 2×100 ml methylene chloride. The combined organic layers were washed with 100 ml 10% ammonium hydroxide solution, 100 ml water, dried over magnesium sulfate, filtered and concentrated under vacuum to a clear colorless oil. The oil was dissolved in 350 ml DMF, Merrifield resin (100 gm. 2% dvb, 200-400 mesh, 1.0 mmol/gm) was added and the stirred mbdure was heated at 100° C. for 16 hours. After cooling, the resin was filtered, washed with 2×200 ml DMF, 2 times 300 ml THF, and dried in a 50° C. vacuum oven for 20 hours. IR 2131 cm -1 .
Reaction
Into a glass screw topped vial was placed 50 μl of a 0.050M solution of the acid in 1,2-dichloroethane (2.5 umol), followed by 50 μl of 0.050M compound II in 1,2-dichloroethane (2.5 μmol), followed by 30 μl 0.017M DMAP in 1,2-dichloroethane (0.5 μmol), followed by 25 mg polymer bound 1-(3-dimethylaminopropyl)-3ethylcarbodiimide (@1.0 μmol/gm=25 μmol). After shaking at 20° C. for 16 hours, 1 μl was removed and diluted to 100 μl with methanol for RPHPLC and MS analysis. The polymer was removed by filtration and the filtrate was concentrated to dryness under vacuum.
EXAMPLE 40
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(naphthalen-2-yl-acetyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide was made by reacting compound II with naphthalene-2-ylacetic acid in the presence of polymer bound EDC as described in METHOD B above.
MS (Cl): 565 (M+H + )
EXAMPLES 41-97
The following compounds were made by reacting compound II with the appropriate corresponding carboxylic acid in the presence of polymer bound EDC, according to methods analogous to that described in Example 40.
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2,2-dimethyl-propionyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 481 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylicacid 2-(2,2-dimethyl-pentanoyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 509 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-hydroxy-2-phenyl-propionyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 545 (M+H + )
4'-Trifluoromethylbiphenyl-2-carboxylic acid 2-(2-phenyl-butyryl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 543 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-methyl-4-oxo-pentanoyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 509 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2-ethyl-butyryl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 495 (M+H + )
4'-Trifluoromethyl-biphenyl-2-boxylic acid (2-ethoxyacetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 483 (M+H + )
4'-Trifluoromethyl-biphenyl-2-oarboxylic acid {2- (4-fluoro-phenyl)-acetyl!-1,2,3,4-tetrahydroisoquinolin-6-yl}-amide
MS (Cl): 533 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-phenylthioacetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 547 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-benzylthioacetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 561 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-methyl-butyryl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 481 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-chloro-butyryl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 501 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-but-3-enoyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 465 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1-cetyl-pyrrolidine-2-carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 536 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid { 2 - (4-oxo-2-thioxo-thiazolidin-3-yl)-acetyl!-1,2,3,4-tetrahydroisoquinolin-6-yl}-amide
MS (Cl): 570 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(pyridine-4-carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 502 (M+H + )
4'-Trifluoromethyl-biphenyl-2-rboxylic acid 2-(quinoline-2-carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 552 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1-phenyl-cyclopentane-carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 569 (M+H + )
4'-Trifluoromethybiphenyl-2-carboxylic acid 2-(a-methoxy-pheny-acetyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 545 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic aid 2-(3-chloro2,2-dimethylpropionyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!amide
MS (Cl): 515 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-cyanoacetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 464 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-methoxyacetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 469 (M+H + )
4'-Trifluoromethyl-biphenyl-2-coxylic acid {2- (4-chloro-phenyl)-acetyl!-1,2,3,4-tetrahydroisoquinolin-6-yl}-amide
MS (Cl): 549 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carbcxylic acid (2-ethyfthioacetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 499 (M+H + )
4'-Trifluoromethyl-biphenyl-2-caboxyic acid 2-(3-phenyl-prop-2-ynoyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 525 (M+H + )
4-Trifluoromethyl-biphenyl-2-coxylic acid 2-(3hydroxy-butyryl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 483 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid {2- (1H-indol-3-yl)acetyl!-1,2,3,4-tetrahydroisoquinolin-6-yl}-amide
MS (Cl): 554 (M+H + )
4-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(6-methyl-pyridine-2-carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!amide
MS (Cl): 516 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(pyridin-2-yl-acetyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 516 (M+H + )
1 H NMR (300 MHz, CDCl 3 ) δ 4.67 (s, 2H); 3.99 (s, 2H); 3.77 (m, 2H); 2.76 and 2.65 (t, 2H).
4'-Trifluoromethyl-biphenyl-2-carboxylic acid {2- (4-nitro-phenyl)-acetyl!-1,2,3,4-tetrahydroisoquinolin-6-yl}-amide
MS (Cl): 560 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(6-diethylcarbamoyl-cyclohex-3-enecarbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 604 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(adamantane-1-carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 559 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid {2- (3-chloro-phenyl)-acetyl!-1,2,3,4-tetrahydroisoquinolin-6-yl}-amide
MS (Cl): 549 (M+H+)
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-diphenylacetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 591 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid {2- (2,4-dichloro-phenyl)-acetyl!-1,2,3,4-tetrahydroisoquinolin-6-yl}-amide
MS (Cl): 583 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2-phthalimido-acetyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 584 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(biphenyl-4-yl-acetyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 591 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-o-tolylacetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 529 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-m-tolylacet yl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 529 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(4-phenyl-but-3-enoyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 541 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(cyclopent-1-enylacetyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 505 (M+H + )
4'-Trifluoroethyl-biphenyl-2-carboxylic acid {2- (3,4,5-methoxy-phenyl)-acetyl!-1,2,3,4-tetrahydroisoquinolin-6-yl}-amide
MS (Cl): 605 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(adamant-1-yl-acetyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 573 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(9H-fluorene9-carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 589 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid {2- (3-trifluoromethyl-phenyl)-acetyl!-1,2,3,4-tetrahydroisoquinolin-6-yl}-amide
MS (Cl): 583 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1-methyl-cyclohexane-carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 521 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid {2- 2-(1,3-dioxo-1,3dihydro-isoindol-2-yl)-propionyl!-1,2,3,4-tetrahydroisoquinolin-6-yl}-amide
MS (Cl): 598 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(4-methyl-2-oxo-pentanoyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 509 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-methoxy-cyclohexanecarbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 537 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-hex-3-enoyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 493 (M+H + )
2-{6- (4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-di hydro-1H-isoquinoline-2-carbonyl}-pyrrolidine-1-carboxylic acid tert-butyl ester
MS (CI): 594 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(tetrahydro-furan-3-carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 495 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(a-oxo-thiophen-2-yl-acetyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 552 (M+NH 4 + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(thiophen-3-yl-acetyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 521 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid {2- (6-methoxy-3-oxo-indan-1-yl)-acetyl!-1,2,3,4-tetrahydroisoquinolin-6-yl}-amide
MS (Cl): 600 (M+2)
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1-acetyl-pyrrolidine-2-carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 536 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(bicyclo 2.2.1!hept-2-yl-acetyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 533 (M+H + )
EXAMPLE 98
Compound II (200 mg, 0.50 mmol), picolinic acid (62 mg, 0.60 mmol) and EDCl (116 mg, 0.60 mmol) were mixed in 10 ml methylene chloride for 14 hrs. Reaction was concentrated and purified by flash chromatography on silica gel (eluent: 70-100% EtOAc/Hex). The product was 4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(pyridine-2-carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide, 98% yield.
MS (Cl): 502 (M+H + );
1 H NMR (250 MHz, CDCl) δ 4.81 and 4.69 (s, 2H); 3.92 and 3.73 (t, 2H); 2.83 (m, 2H).
METHOD C
Into a glass screw topped vial was placed 150 μl of a 0.020M solution of the isocyanate in 1,2-dichloroethane (3.0 μmol), followed by 83 μl of 0.030M 4'-trifluoromethyl-biphenyl-2-carboxylic acid (1,2,3,4-tetrahydroisoquinolin-6-yl)-amide (compound II) in 1,2-dichloroethane (2.5 μmol) After shaking at 20° C. for 16 hours, 10 μl was removed and diluted to 100 μl with methanol for RPHPLC and MS analysis. The reaction was concentrated to dryness under vacuum.
EXAMPLE 99
6- (4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro1H-isoquinoline-2-carboxylic acid phenylamide was made as described in Method C by reacting compound II with phenyl isocyanate.
MS (Cl): 516 (M+H + );
1 H NMR (250 MHz, DMSO) δ 4.56 (s, 2H); 3.66 (t, 2H); 2.77 (t, 2H).
EXAMPLES 100-103
The following compounds were made by reacting compound II with the appropriate corresponding isocyanate according to methods analogous to those described in Example 99.
6- 4'-Trifluoromethylbiphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-1soquinoline-2-carboxylic acid hexylamide
MS (Cl): 524 (M+H + )
({6- (4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinoline-2-carbonyl}-amino)-acetic acid ethyl ester
MS (Cl): 526 (M+H + )
6- (4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzylamide
MS (Cl): 530 (M+H + )
6 (4'-Trifluoromethyl-biphenyl-2carbonyl)-amino!-3,4-dihydro-1H-isoquinoline-2-carboxylic acid (R)-1-phenyl-ethyl!-amide
Note: Product made as described in Method C using compound II and (R)-(+)-α-methylbenzyl isocyanate.
MS (Cl): 544 (M+H + );
1 H NMR (250 MHz, CDCl 3 ) δ 5.06 (m, 1H); 4.66 (d, 1H); 4.46 (s, 2H); 3.56 (t,2H); 2.78 (t, 2H); 1.52 (d, 3H).
EXAMPLE 104
6- (4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinoline-2-carboxylic acid pyridin-2-ylamide was prepared by a method analogous to the procedure described in Ohsawa, A.; Arai, H.; Igeta, H. Chem. Pharm. Bull. 1980, 28, 3570.
23% yield;
MS (Cl): 517 (M+H + );
1 H NMR (300 MHz, CDCl 3 ) δ 4.60 (s, 2H); 3.69 (t, 2H); 2.86 (t, 2H).
METHOD D
Into a glass screw topped vial was placed 150 μl of a 0.020M solution of the sulfonyl chloride in 1,2-dichloroethane (3.0 μmol), followed by 83 μl of 0.030M compound II in 1,2-dichloroethane (2.5μmol), followed by 25 mg polymer bound morpholinomethylpolystyrene(@2.5 mmol/gm=62 μmol). After shaking at 20° C. for 16 hours, 10 μl was removed and diluted to 100 μl with methanol for RPHPLC and MS analysis. The polymer was removed by filtration and the filtrate was concentrated to dryness under vacuum.
EXAMPLE 105
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(naphthalene-1-sulfonyl)-1,2,3,4-tetrahydroisoquinolin6-yl!-amide was prepared by METHOD D reacting compound II with naphthalene-1-sulfonyl chloride.
MS (Cl): 604 (M+NH 4 + )
EXAMPLES 106-111
The following compounds were prepared by METHOD D as in Example 105, by reacting compound II with the appropriate correspondin sulfonyl chloride.
2-{6- (4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4dihydro-1H-isoquinoline-2-sulfonyl}-benzoic acid methyl ester
MS (Cl): 595 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(propane-2-sulfonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl! -amide
MS (Cl): 520 (M+NH 4 + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-chloro-propane-1-sulfonyl)-1,2,3,4tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 555 (M+NH 4 + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(butane-1-sulfonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 534 (M+NH 4 + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-dimethylsulfamoyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 521 (M+NH 4 + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2-trifluoromethoxy-benzenesulfonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 638 (M+NH 4 + )
EXAMPLE 112
This example illustrates how to make a compound where the group in XYZ linking XYZ to the tetrahydroisoquinoline ring is thiocarbamoyl.
Into a glass screw topped vial was placed 150 μl of a 0.020M solution of the thioisocyanate (cyclopropyihioisocyanate) in 1,2-dichloroethane (3.0 umol), followed by 83 μl of 0.030M 4'-trifluoromethyl-biphenyl-2 carboxylic acid (1,2,3,4-tetrahydroisoquinolin6-yl)-amide in 1,2-dichloroethane (2.5 μmol) After shaking at 20° C. for 16 hours, 10 μl was removed and diluted to 100 μl with methanol for RPHPLC and MS analysis. The reaction was concentrated to dryness under vacuum, yielding 4'-trifluoromethyl-biphenyl-2-carboxylic acid (2-cyclopropylthiocarbamoyl-1,2,3,4tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 496 (M+H + )
METHOD F
A solution of aldehyde (7.5 μmol), compound II (5μmol), acetic acid (7.5 μmol), and sodium triacetoxyborohydride (10 μmol) in 300 μl of 1,2-dichloroethane was shaken for 60 hr at room temperature. A 7.5 μl sample was removed and diluted with 93 μl of methanol for TLC and MS analysis. The remaining sample was evaporated to dryness in vacuo. The crude solid was dissolved in 500 μl of ethyl acetate and washed with 300 μl of 5% sodium bicarbonate. The organic layer was concentrated to dryness under vacuum.
EXAMPLE 113
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2,6,6trimethyl-cyclohexyl-2-enylmethyl)-1,2,3,4-tetrahydroisoquinolin-6yl!-amide was made as described in METHOD F by reacting compound II with 2,6,6-trimethylcyclohex-2-enyl aldehyde.
MS (Cl): 533 (M+H + )
EXAMPLES 114-162
The following compounds were made as in Example 113 by METHOD F by reacting compound II with the appropriate corresponding aldehyde.
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-cyclohex3-enylmethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 491 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-methyl-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (CI): 501 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(4-dimethylamino-benzyl)-1,2,3,4tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 530 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(4methoxy-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 517 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2-fluoro-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 505 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3,4-dichloro-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 555 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(4-isopropyl-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 529 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-biphenyl-4-ylmethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 564 (M+2)
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-phenoxy-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 580 (M+2)
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(4methoxy-naphthalen-1-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 568 (M+2)
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-naphthalen-1-ylmethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 538 (M+2)
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(4-methylthio-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 533 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(9-ethyl-9H-carbazol-3-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 605 (M+2)
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(4-tert-butyl-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 544 (M+2)
3-{6- (4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinolin-2-ylmethyl}-cyclohexanecarboxylic acid ethyl ester
MS (Cl): 566 (M+2)
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2-tert-butylthio-benzyl)-1,2,3,4-tetrahydroisoquinolin6-yl!-amide
MS (Cl): 576 (M+2)
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-cyclohexylmethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 494 (M+2)
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-fluoro-benzyl)-1,2,3,4-tetrahydroisoquinolin-6yl!-amide
MS (Cl): 505 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-benzo 1,3!dioxol-5-ylmethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 531 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-naphthalen-2-ylmethyl-1,2,3,4-tetrahydroisoquinolin-6yl)-amide
MS (Cl): 538 (M+2)
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2-methoxy-naphthalen-1-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 568 (M+2)
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(4benzyloxy3methoxy-benzyl)-1,2,3,4-tetrahydroisoquinolin-6yl!-amide
MS (Cl): 624 (M+2)
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1,3,4-trimethyl-cyclohexyl-3-enylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 533 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid {2- 2-(4-chloro-phenylthio)-benzyl!-1,2,3,4-tetrahydroisoquinolin-6-yl}-amide
MS (Cl): 629 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2,4dichloro-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 555 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1,5a,6,9,9a,9b-hexahydro-4H-dibenzofuran-4a-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 585 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid {2- 4(2-diethylamino-ethoxy)-benzyl!-1,2,3,4-tetrahydroisoquinolin-6-yl}-amide
MS (Cl): 603 (M+2)
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2-trifluoromethyl-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 555 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(6,6-dimethyl-bicyclo 3.1.1!hept-2-en-2-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 531 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2-benzyloxy-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 594 (M+2)
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(4-phenoxy-benzyl)-1,2,3,4- tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 579 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(4-dimethylamino-naphthalen-1-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 580 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(4-pyrrolidine-1-yl-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 557 (M+2)
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-thiophen-2-ylmethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 493 (M+H + );
1 H NMR (250 MHz, DMSO) δ 3.83 (s, 2H); 3.52 (s, 2H); 2.69 (m, 4H).
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1H-indol-3-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 526 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1H-pyrrol-2-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 476 (M+H + );
1 H NMR (300 MHz, DMSO) δ 3.54 (s, 2H); 3.43 (s, 2H); 2.72 (m, 2H); 2.60 (m, 2H).
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-furan-2-ylmethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 477 (M+H + );
1 H NMR (250 MHz, DMSO) 3.65 (s, 2H); 3.47 (s, 2H); 2.71 (m, 2H); 2.65 (m, 2H).
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-ylm ethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 598 (M+2)
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-ylmethyl)-1,2,3,4tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 581 (M+2)
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3,5-dimethyl-1phenyl-1H-pyrazol-4-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 582 (M+2)
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-benzofuran-2-ylmethyl-1,2,3,4-tetrahydroisoquinolin-6yl)-amide
MS (Cl): 527 (M+H + )
Aceticacid5-{6- (4'-trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinolin-2-ylmethyl}-furan-2-ylmethyl ester
MS (Cl): 549 (M+H + );
1 H NMR (300 MHz, CDCl 3 ) δ 5.02 (s, 2H); 3.70 (s, 2H); 3.60 (s, 2H); 2.83 (t, 2H); 2.75 (t, 2H); 2.07 (s, 3H).
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-methyl-thiophen-2-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 507 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-thiophen3-ylmethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
MS (Cl): 493 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2-methyl-1H-indol-3-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 540 (M+H + )
2-Methyl-{6- (4'-trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinolin-2-ylmethyl}-furan-3-carboxylic acid ethyl ester
MS (Cl): 563 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2,5methyl-thiophen-3-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 541 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1methyl-1H-indol-3-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
MS (Cl): 557 (M+NH 4 + )
2-{6- (4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-di hydro-1H-isoquinolin-2-ylmethyl}-cyclopropanecarboxylic acid ethyl ester
MS (Cl): 523 (M+H + )
METHOD G
The following compounds were made via reductive amination by methods analogous to the procedure described in Abdel-Magid, A. F.; Maryanoff, C. A.; Carson, K. G. Tetrahedron Lett. 1990, 31, 5595. This procedure is essentially the same as METHOD F and employs sodium triacetoxyborohydride, except that certain modifications, generally in the choice of solvent and reaction temperature have been made, all modifications being noted for each compound. In addition, unless otherwise noted, 1.5-2 equivalents of carbonyl compound was used. For compounds made in this section, it is noted that the free base was isolated. For use in biological screens the free base was, in most cases, converted to the mono-hydrochloride salt by conventional methods.
EXAMPLE 163
4'-Trifluoromethyl-biphenyl-2carboxylic acid (2-benzyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide was made by reacting compound II with benzaldehyde, using a method analogous to that described in Abdel-Magid et al. above, with the following modifications:
Solvent: DCE
56% yield
MS (Cl): 487 (M+H + )
1 H NMR (250 MHz, DMSO) δ 3.62 (s, 2H); 3.46 (s, 2H); 2.74 (m, 2H); 2.63 (m, 2H).
EXAMPLES 164-193
The following compounds were made by reacting compound II with the appropriate corresponding aldehyde using methods analogous to that disclosed in Abdel-Magid et al., with appropriate modifications noted.
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-pyridin-2-ylmethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
Solvent THF
62% yield
MS (Cl): 488 (M+H + )
1 H NMR (300 MHz, CDCl 3 ) δ 3.82 (s, 2H); 3.63 (s, 2H); 2.84 (m, 2H); 2.77 (m, 2H).
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-pyridin-3-ylmethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
Solvent: THF
MS (Cl): 488 (M+H + )
4'-Trifluoromethyl-biphenyl-2carboxylic acid (2-pyridin-4-ylmethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
Solvent: THF
MS (Cl): 488 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-quinolin-2-ylmethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
Solvent: DCE
66% yield
MS (Cl): 538 (M+H + )
1 H NMR (250 MHz, CDCl 3 ) δ 3.99 (s, 2H); 3.67 (s, 2H); 2.82 (s, 4H).
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(6methyl-pyridin-2-ylmethyl)-1,2,3,4tetrahydroisoquinolin-6-yl!-amide
Solvent: DCE
63% yield
MS (Cl): 502 (M+H + )
1 H NMR (250 MHz, CDCl 3 ) δ 3.79 (s, 2H); 3.63 (s, 2H); 2.81 (s, 2H); 2.76 (s, 2H); 2.55 (s, 3H).
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(6-bromo-pyridin-2-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
Solvent: DCE
MS (Cl): 568 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(6-formyl-pyridin-2-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
Solvent: DCE; 10 equiv. of aldehyde used
MS (Cl): 516 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(2-chloro-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
Solvent: DCE
MS (Cl): 521 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-chloro-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
Solvent: DCE
69% yield
MS (Cl): 521 (M+H + )
1 H NMR (300 MHz, DMSO) δ 3.64 (s, 2H); 3.47 (s, 2H); 2.74 (t, 2H); 2.64 (t, 2H).
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(4-chloro-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
Solvent: DCE
MS (Cl): 521 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-pyrimidin-2-ylmethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
Solvent: Methylene chloride; 6 equiv. of aldehyde used
61% yield
MS (Cl): 489 (M+H + )
1 H NMR (250 MHz, DMSO) δ 3.87 (s, 2H); 3.60 (s, 2H); 2.77 (m, 4H).
4'-Trifluoromethyl-bipheny-2-carboxylic acid 2-(3-nitro-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
Solvent: DCE
76% yield
MS (Cl): 532 (M+H + )
1 H NMR (300 MHz, CDCl 3 ) δ 3.75 (s, 2H); 3.58 (s, 2H); 2.84 (t, 2H); 2.73 (t, 2H).
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-methoxy-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
Solvent: DCE
MS (Cl): 517 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-trifuoromethyl-benzyl)-1,2,3,4tetrahydroisoquinolin-6-yl!-amide
Solvent: DCE
MS (Cl): 555 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-cyano-benzyl)-1,2,3,4-tetrahydroisoquinolin6-yl!-amide
Solvent: DCE
MS (Cl): 512 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-hydroxy-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
Solvent: DCE
MS (Cl): 503 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3,5-dichloro-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
Solvent: DCE
MS (Cl): 556 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3,5-bis-trifluoromethyl-benzyl)-1,2,3,4tetrahydroisoquinolin-6-yl!-amide
Solvent: DCE
MS (Cl): 622 (M+H + )
Aceticacid3-{6- (4'-trifluoromethyl-biphenyl-2-carbonyl)-amino!-3,4-dihydro-1H-isoquinolin-2-ylmethyl}-phenyl ester
Solvent: DCE
MS (Cl): 545 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-sulfamoyl-benzyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
Solvent: DCE
MS (Cl): 566 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1H-imidazol-2-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
Solvent: 7:3 THF:DCE
59% yield
MS (Cl): 477 (M+H + )
1 H NMR (300 MHz, CDCl 3 ) δ 3.79 (s, 2H); 3.58 (s, 2H); 2.82 (m, 2H); 2.74 (m, 2H).
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1-methyl-1H-pyrrol-2-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
Solvent: DCE
57% yield
MS (Cl): 490 (M+H + )
1 H NMR (260 MHz, CDCl 3 ) 63.64 (s, 3H); 3.57 (s, 2H); 3.51 (s, 2H); 2.77 (t, 2H); 2.65 (t, 2H).
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1H-benzoimidazol-2-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
Solvent: DCE
83% yield
MS (Cl): 527 (M+H + )
1 H NMR (250 MHz, DMSO) δ 3.89 (s, 2H); 3.58 (s, 2H); 2.76 (m, 4H).
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1H-imidazol4-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
Solvent: DCE
66% yield
MS (Cl): 477 (M+H + )
1 H NMR (250 MHz, DMSO) δ 3.56 (s, 2H); 3.46 (s, 2H); 2.72 (m, 2H); 2.63 (m, 2H).
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-thiazol-2-ylmethyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
Solvent: DCE
38% yield
MS (Cl): 494 (M+H + )
1 H NMR (250 MHz, DMSO) δ 3.99 (s, 2H); 3.64 (s, 2H); 2.76 (s, 4H).
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-methyl-benz b!thiophen-2-ylmethyl)-1,2,3,4tetrahydroisoquinolin-6-yl!-amide
Solvent: DCE
MS (Cl): 557 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1methyl-1H-imidazol-2-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
Solvent: 7:3 THF:DCE
72% yield
MS (Cl):. 491 (M+H + )
1 H NMR (300 MHz, DMSO) δ 3.66 (s, 2H); 3.63 (s, 3H); 3.47 (s, 2H); 2.70 (m, 2H); 2.62 (m, 2H).
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(3-methyl-3H-imidazol-4ylmethyl)-1,2,3,4tetrahydroisoquinolin-6-yl!-amide
Solvent: THF
MS (Cl): 491 (M+H + )
4'-Trifluoromethyl-biphenyl-2-carboxylic acid 2-(1H- 1,2,4!triazol-3-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl!-amide
Solvent: EtOH; Temp: 70° C.
42% yield
MS (Cl): 478 (M+H + )
1 H NMR (250 MHz, CDCl 3 ) δ 3.87 (s, 2H); 3.63 (s, 2H); 2.79 (s, 4H).
4'-Trifluoromethyl-biphenyl-2-carboxylic acid (2-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-amide
Solvent: THF; 3 equiv. of aldehyde used
MS (Cl): 411 (M+H + )
EXAMPLE 194
This example demonstrates how to make a compound of formula II as illustrated in Scheme 2. Numbers in parentheses with each title compound correspond to numbers in Scheme 2.
a. 2-(carboxy-5-nitro-phenyl)malonic acid dimethyl ester (2)
A solution of 2-chloro-4-nitrobenzoic acid (75 g, 372 mmol) in dimethyl malonate (900 mL) was sparged with nitrogen for 15 min. Sodium methoxide (48.3 g, 894 mmol) was added in one portion and the contents exothermed to 480° C. Fifteen minutes later, copper (I) bromide (5.4 g, 37 mmol) was added in one portion and the contents heated to 70° C. for 24 hrs. The reaction was 70% complete by nmr, the contents heated to 85° C. for 6 hrs to completely consume the 2-chloro-4-nitrobenzoic. Water (900 mL) was added to the cooled reaction followed by hexanes (900 mL). The aqueous layer was separated, toluene (900 mL) added, filtered through celite, and aqueous layer separated. Fresh toluene (1800 mL) was added to the aqueous layer and the biphasic mixture acidified with 6N aqueous HCl (90 mL). A white precipitate formed and the contents stirred for 18 hrs. The product was filtered off and dried to give a white soid (78.1 g, 70%) mp=153° C.
1 H NMR (CD 3 ) 2 SO δ 78.37 (d, J=2 Hz, 1H), 8.30 (d, J=1 Hz, 2H), 5.82 (s, 1H), (3.83 (s, 6H).
13 C NMR (CD 3 ) 2 SO δ 168.0, 167.3, 149.4, 137.1, 135.8, 132.5, 125.4, 123.7, 54.5, 53.4.
Anal. Calcd for C 11 H 10 NO 8 : C, 48.49; H, 3.73; N, 4.71. Found: C, 48.27; H. 3.72; N, 4.76.
b. 2-carboxymethyl-4-nitro-benzoic acid (3)
To a solution of 2-(carboxy-5-nitro-phenyl)malonic acid dimethyl ester, (25.0 g, 84 mmol) in methanol (200 mL), sodium hydroxide (5 g, 125 mmol) in water (200 mL) was added. After 3 hrs the reaction was complete, the methanol removed under vacuum, contents cooled to 0° C. and acidified with concentrated HCl (37 mL). The aqueous layer was extracted twice with ethyl acetate (200 mL then 100 mL), the combined organic layers dried with magnesium sulfate, most of the solvent removed under vacuum, and methylene chloride (30 mL) was then added. The white solid was filtered off and dried to give 19.3 g of product as a white solid, mp=180-82° C. IR(KBr) 3080, 3055, 2983, 1707, 1611, 1585, 1516, 1491, 1424, 1358; 1298, 1237 cm -1 .
13 C NMR (CD 3 ) 2 SO δ 172.3, 167.5, 149.2, 138.8, 137.3, 132.1, 127.2, 122.4, 39.8.
Anal. Calcd for C 9 H 17 NO 6 : C, 48.01; H, 3.13; N, 6.22. Found: C, 47.67; H, 3.19; N, 6.31.
c. 2-(2-hydroxymethyl-5-nitro-phenyl)-ethanol (4)
A THF (60 mL) solution of 2-carboxymethyl-4-nitro-benzoic acid (3.0 g , 13.3 mmol) was treated with borane-THF complex (53.3 mL, 53.3 mmol) over 15 min at 0° C. The reaction was stirred for 18.5 hrs, quenched with THF/water (1:1, 30 mL), water (20 mL) added and the layers separated. The aqueous layer was reextracted with THF (30 mL); the combined organic phase washed with brine, dried with magnesium sulfate, and solvent removed under vacuum to give the product as a white solid (2.06 g, 78%) mp=79-81° C.
IR(KBr) 3277, 3192, 2964, 2932, 1614, 1525, 1507, 1170, 1134, 1089, 1067 cm- 1 .
13 C NMR (CD 3 ) 2 SO δ 149.1, 146.6, 139.2, 127.8, 124.31 121.3, 61.2, 60.6, 34.9.
Anal. Calcd for C 9 H 11 NO 4 : C, 54.82; H, 5.62; N, 7.10. Found: C, 54.54, H, 5.49;
N, 7.07.
c. 2-(2-hydroxymethyl-5nitro-phenyl)-ethanol (4), alternative procedure
A mixture of 2 carboxymethyl-4-nitro-benzoic acid (13 g, 57.7 mmol), acetic anhydride (5.45 mL, 57.7 mmol) and toluene (30 mL) were heated to reflux for 5 hrs. The solvent was removed under vacuum to yield 6-nitro-isochroman-1,3-dione (compound (3a) in Scheme 2) as a yellow solid (10.51 g, 88%). Borane tetrahydrofuran complex (35.6 mL, 1M in THF) was added dropwise over 40 min to a solution of 6nitro-isochroman-1,3-dione (2 g, 9.66 mmol) in THF (40 mL) at 0° C. The contents were stirred for 18 hrs at 25° C., cooled to 0° C., quenched with methanol (30 mL), and stirred for 1 hr. The solvents were removed under vacuum, ethyl acetate (30 mL) added and the organic phase washed with 10% aqueous hydrochloric acid. The aqueous acidic layer was reextracted with ethyl acetate (30 mL), the combined organic layers dried with magnesium sulfate, and evaporated under vacuum until 2 mL of ethyl acetate remained. This solution was filtered through silica gel washing with methylene chloride (30 mL) to remove impurities. The silica gel was flushed with ethyl acetate, solvent removed under vacuum to give a solid which was slurryed in methylene chloride and filtered to afford the diol as a white solid, 1.38 g, 73%.
d. 6-nitro-1,2,3,4-tetrahydro-isoquinoline (5)
Methanesulfonyl chloride (0.9 mL, 11.63 mmol) was added dropwise over 10 min to a solution of 2-(2-hydroxymethyl-5-nitrophenyl)-ethanol (1.0 g, 5.07 mmol), triethyl amine (1.8 mL, 12.91 mmol), in methylene chloride (20 mL). TLC showed complete reaction after 30 min. 1 H NMR (CD 3 Cl) δ 8.17-11 (m, 2H), 7.65 (d, J=9 Hz, 1H), (s, 2H), 4.49 (t, J=6 Hz, 2H), 3.25 (t, J=6 Hz, 2H), 3.08 (s, 3H), 2.98 (s, 3H). reaction mixture was washed with 10% aqueous HCL, saturated aqueous sodium bicarbonate, and brine. The organic layer was dried with magnesium sulfate, methylene chloride removed under vacuum and chased with THF (3×100 mL). The product 1.9 g was employed directly in the next reaction without further purification. Ammonia (50 mL) was added to the dimesylate (1.9 g) in THF (30 mL) at -78° C. The contents were warmed to 24° C. for 60 hrs, ammonia distilled out, and solvent removed under vacuum to give the crude product (786 mg, 82%). Toluene was added and the solution was filtered through magnesium sulfate, and solvent removed under vacuum to yield 721 mg (75%) of an amber oil.
1 H NMR (CDCl 3 ) δ 7.97 (s, 1H), 7.95 (d, J=9 Hz, 1H), 7.15 (d, J=9 Hz, 1H), 4.07 (s, 2H), 3.15 (t, J=6 Hz, 2H), 2.89 (t, J=6 Hz, 2H), 1.98 (bs, 1H).
e. 6-nitro-3,4-dihydro-1H-isoquinoline2-carboxylic acid tert-butyl ester (6)
To a solution of 6-nitro-1,2,3,4-tetrahydroisoquinoline (840 mg, 4.71 mmol) in methylene chloride (17 mL) containing triethylamine (0.72 mL), 5.17 mmol) was added BOC-anhydride (1.44 mL, 6.26 mmol). Saturated aqueous sodium bicarbonate was added 5 hr later, the phases separated, organic layer dried with magnesium sulfate, and solvent removed under vacuum to give the product as a pale white solid (1.2 g, 92%). mp=138-41° C.
IR(KBr) 3056, 3018, 2982, 2935, 1734, 1684, 1612, 1522, 1399, 1236 cm -1 . 1 H NMR (CDCl 3 ) δ 8.04 (t, J=5 Hz, 1H), 8.01 (s, 1H), 7.26 (t, J=5 Hz, 1H), (s, 2H), 3.68 (t, J=6 Hz, 2H), 2.93 (t, J=6 Hz, 2H), 1.49 (s, 9H).
f. 6-amino-3,4-hydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (7)
The 6-nitro-3,4dihydro-1H-isoquinoline-2-carboxylic acid tert-utyl ester (82 mg, 0.29 mmol) in THF (2 mL) was hydrogenated with 5%Pt-C (50% water wet, 10 mg) at 50 psi for 5 hrs. The catalyst was filter off, solvent removed under vacuum and chromatographed on silica with ethyl acetate / hexanes to give 42 mg (57%) of the product.
IR(KBr) 3005, 2975, 2928, 1685, 1627, 1509, 1423, 1365, 1166 cm -1 .
1 H NMR (CDCl 3 ) δ 6.90 (d, J=6 Hz, 1H), 6.56 (d, J=6 Hz, 1H), 6.48 (s, 1H), 4.47 (s, 2H), 3.60 (m, J=6 Hz, 4H), 2.73 (t, J=6 Hz, 2H), 1.49 (s, 9H).
The product made as in Example 194 above can be reacted with 4'-trfluoromethyl-biphenyl-2-carboxylic acid as disclosed in Example 1 to afford the N-blocked compound II, then deblocked to yield compound II.
EXAMPLE 195
This example demonstrates how to make compound II as shown in Scheme 3. Numbers in parentheses correspond to those in Scheme 3.
a. 4'-trifluoromethyl-biphenyl-2-carbonyl chloride
A solution of 4(trifluoromethyl)-2-biphenylcarboxylic acid (9.08 g, 34 mmol), thionyl chloride (12 mL) and dimethylformamide (0.05 mL) was heated to reflux for 2 hrs. The reaction was complete by NMR. Thionyl chloride was distilled by displacing with toluene (56 mL). Solvent was removed under vacuum to give the acid chloride as a white solid (9.46 g, 97%).
1 H NMR (CDCl 3 ) δ 8.12 (dd, J=1 Hz, J=8 Hz, 1H), 7.70-7.37 (m, 7H). 13 C NMR CD 3 Cl δ (CO) 168.
b. 4'-trifluoromethyl-biphenyl-2-carboxylic acid- 3-(2-hydroxy-ethyl)-4-hydroxymethyl-phenyl!-amide (10)
Pt-C (50% water wet, 200 mg) was added to a THF (40 mL) solution of 2-(2 hydroxymethly-5-nitro-phenyl)-ethanol (1.0 g, 5 mmol) and the reaction hydrogenated at 50 psi for 2 hrs. NMR showed complete reaction to form 2-(5-amino-2-hydroxymethyl-phenyl)-ethanol (compound (9) in Scheme 3);
1 H NMR (CD 3 Cl) δ 7.08 (d, J=2 Hz, 1H), 6.54-6.50 (m, 2H), 4.51 (s, 2H), 3.82 (t, J=6 Hz, 2H), 3.80-2.95 (bs, 4H), 2.84 (t, J=6 Hz, 2H).
The catalyst was filtered off, triethylamine (1.4 mL, 10 mmol) added, followed by dropwise addition of a THF (10 mL) solution of the 4'-trifluoromethyl-biphenyl-2-carbonyl chloride (1.44 g, 5 mmol) over 1 hr. The contents were stirred for 24 hrs, the solvent removed under vacuum, and ethyl acetate (40 mL) added. The organic phase was washed with water (2×40 mL), dried with magnesium sulfate, solvent removed under vacuum, and chased with toluene (3×40 mL). Upon removal of the solvent 2.11 g a white solid was obtained which was repulsed in methylene chloride (21 mL) for 18 hrs, the product filtered off, and dried to give the title product as a white solid 1.71 g (81%).
1 H NMR (CD 3 ) 2 SO δ 10.22 (s, 1H), 7.73 (d, J=8 Hz, 2H), 7.62-28 (m, 8H), 7.20 (d, J=8 Hz, 1H), 4.96 (bs, 1H), 4.69 (bs, 1H), 4.43 (s, 2H), 3.51 (t, J=7 Hz, 2H), 2.67 (t, J=7 Hz, 2H).
IR(KBr) 3264, 3232, 31278, 3124, 3106, 2956, 2928, 1649, 1613, 1533, 1328, 1129 cm -1 .
13 C NMR (CD 3 ) 2 SO δ (amide CO) 167.7, aliphatic carbons 62.3, 61.1, 36.0.
Anal. Calcd for C 23 F 3 H 20 NO 3 : C, 66.50; H, 4.85; N, 3.37. Found: C, 66.29; H, 4.79; N, 3.27.
c. 4'-trifluoromethyl-biphenyl-2-carboxylic acid (1,2,3,4-tetrahydroisoquinolin-6-yl)-amide (compound 11).
Methanesulfonyl chloride (0.085 mL) was added to a 0° C. solution of 4'-trifluoromethyl-biphenyl-2-carboxylic acid- 3-(2-hydroxy-ethyl)-4-hydroxylmethyl-phenyl!-amide (214 mg, 0.51 mmol) and triethylamine (0.18 mL) in THF (8.5 mL). TLC showed complete reaction after 30 min. The contents were cooled to -78° C. and ammonia was added and the contents stirred for 18 hrs at 250° C. The solvents were removed under vacuum, methylene chloride (10 mL) and aqueous 1N aqueous HCl added and the contents stirred for 1 hr. The phases were separated and the aqueous phase made alkaline with aqueous sodium hydroxide to a pH of 12. The organic phase was extracted with methylene chloride (4×10 mL), solvent removed under vacuum to give a white solid 108 mg which was chromatographed on silica eluting with 5% methanol/methylene chloride with 0.5% ammonium hydroxide. The product was obtained as a white solid (40 mg, 20%).
1 H NMR (CDCl 3 ) δ 7.76-6.83 (m, 11H), 3.89 (s, 2H), 3.52 (d, J=7 Hz, 0.5H), 3.04 (t, J=6 Hz, 2H), 2.74 (m, 0.5H), 2.66 (t, J=7 Hz, 2H), 2.27 (s, 1H).
13 C NMR CD 3 Cl δ (aliphatic carbons only) 47.8, 43.6, 29.1.
Examples 196-197 demonstrate how to make compounds according to the invention as illustrated in Scheme 3.
EXAMPLE 196
4'-trifluoromethyl-biphenyl-2-carboxylic acid (2-benzyl-1,2,3,4-tetrahydroisoquinolin-6yl)-amide
Methanesulfonyl chloride (0.041 mL) was added to a 0° C. solution of 4'-trifluoromethyl-biphenyl-2-carboxylic acid- 3-(2-hydroxy-ethyl)-4-hydroxymethyl-phenyl!-amide (100 mg, 0.24 mmol) and triethylamine (0.084 mL) in THF (2 mL). TLC showed complete reaction after 30 min. Benzylamine (0.132 mL) was added and the contents stirred for 18 hrs at 25° C. and 60 hrs at 50° C. The solvent was removed under vacuum, the residue dissolved in methylene chloride (15 mL), washed with pH9 buffer, phases separated, and the organic phase dried with magnesium sulfate. Removal of the solvent under vacuum gave the crude product as a white solid (204 mg), which was repulsed in CDCl 3 filtered off and dried to give the product as a white solid (46 mg, 39%). mp=230-32° C.
1 H NMR (CD 3 ) 2 SO δ 7.73 (d, J=8 Hz, 2H), 7.60-23 (m, 12H), 7.17 (d, J=8Hz, 1H), 6.87 (d, J=8 Hz, 1H), 3.60 (s, 2H), 3.43 (s, 2H), 2.71 (m, 2H), 2.62 (m, 2H).
Anal. for C 30 F 3 H 25 N 2 O: C, 74.06; H, 5.18; N, 5.76. Found: C, 74.08; H, 5.38; N, 5.76.
EXAMPLE 197
4'-trifluoromethyl-biphenyl-2-carboxylic acid (2-allyl-1,2,3,4-tetrahydroisoquinolin-6yl)-amide
Methanesulfonyl chloride (0.041 mL, 0.53 mmol) was added dropwise to a THF (2 mL) solution of triethylamine (0.084 mL, 0.60 mmol) and 4'-trifluoromethyl-biphenyl-2-carboxylic acid- 3-(2-hydroxy-ethyl)-4-hydroxylmethyl-phenyl!-amide (0.1 g, 0.24 mmol) at -20° C. Fifteen minutes after the addition was complete allylamine (0.09 mL, 1.2 mmol) was added, the contents stirred at 25° C. for 18 hrs and then 70 hrs at 60° C. The solvent was removed under vacuum, methylene chloride (10 mL) added and organic phase washed with pH12 water (10 mL). The organic solvent was removed under vacuum to afford 281 mg of crude product. This material was chromatographed on silica eluting with 10%methanol/methylene chloride to afford the product as a white solid (91 mg, 87%).
1 H NMR (CDCl 3 ) δ 7.80 (d, J=8 Hz, 1H), 7.68 (d, J=8 Hz, 2H), 7.60-7.42 (m, 5H), 6.93-6.83 (m, 3H), 6.00-5.86 (m, 1H), 5.27-5.17 (m, 2H), 3.55 (s, 2H), 3.15 (d, J=7 Hz, 2H), 2.83 (t, J=6 Hz, 2H), 2.69 (t, J=6 Hz, 2H), 1.66 (bs, 1H).
13 C NMR CD 3 Cl δ (aliphatic carbons only) 61.4, 55.6, 50.3, 29.1. | Compounds of formula (I), ##STR1## wherin X is CH 2 , CO, CS or SO 2 ; Y is selected from: a direct link, aliphatic hydrocarbylene radicals having up to 20 carbon atoms, which radical may be mono-substituted by hydroxy, (C 1 -C 10 )alkoxy, (C 1 -C 10 )acyl, (C 1 -C 10 )acyloxy, or (C 6 -C 10 )aryl, NH, and O, provided that if X is CH 2 ,Y is a direct link; Z is selected from the following groups: (1) H, halo, cyano, (2) hydroxy, (C 1 -C 10 )alkoxy, (C 1 -C 10 )a1kylthio, (C 1 -C 10 )acyl, thiophenylcaronyl (C 1 -C 10 )alkoxycarbonyl, (3) (C 1 -C 10 )aklkyammo, di(C 1 -C 10 )alylamino, (C 6 -C 10 )aryl(C 1 -C 10 )alkylamino, provided that Y is not O or NH, (4) unsubstituted vinyl, (C 6 -C 10 )aryl, (C 3 -C 8 )cycloalkyl and fused benz derivatives thereof, (C 7 -C 10 )polycycloalkyl, (C 4 -C 8 )cycloalkenyl, (C 7 -C 10 )polycycloalkenyl, (5) (C 6 -C 10 )aryloxy, (C 6 -C 10 )aryltio, (C 6 -C 10 )aryl(C 1 -C 10 )alkoxy, (C 6 -C 10 )aryl(C 1 -C 10 )alkylthio, (C 3 -C 8 )cycloalkyloxy, (C 4 -C 8 )cycloalkenyloxy, (6) heterocyclyl sclected from the group consisting of monocyclic radicals and fused polycycuic radicals, wherein said radicals contain a total of from 5 to 14 ring atoms, wherein said radicals contain a total of from 1 to 4 ring heteroatoms independently selocted from oxygen, nitrogen, and sulfur, and wherein the individual rings of said radicals may be independendy satated, partally unsaturated, or aromatic, provided that if X is CH 2 , Z is H or is selected from groups (4) and (6), wherein, when Z contains one or more rings, said rings may each independently bear 0 to 4 substituents independently selected from halo, hydroxy, cyano, nitro, oxo, thioxo, aminosulfonyl, phenyl phenoxy, phenylthio, halophenylthio, benzyl, benzyloxy, (C 1 -C 10 )alkyl, (C 1 -C 10 )alkoxy, (C 1 -C 10 )alkoxycarbonyl, (C 1 -C 10 )althyltio, (C 1 -C 10 )altylamino, (C 1 -C 10 )alkylaminocarbonyl, di(C 1 -C 10 )alkylamino, di(C 1 -C 10 )alkylaminocarbonyl, di(C 1 -C 10 )alkyo(C 1 -C 10 )alkoxy, (C 1 -C 3 )perfluoroalkyl, (C 1 -C 3 )perfluoroalkoxy, (C 1 -C 10 )acyl, (C 1 -C 10 )acyloxy, (C 1 -C 10 )acyloxy(C 1 -C 10 )alkyl, and pyrrolidinyl; and pharmaceutically acceptable salts thereof. | 2 |
FIELD OF THE INVENTION
[0001] This invention provides novel chemical agents to reduce polystyrene foam plastics to a compact form using a low vapor pressure dibasic ester-based chemical agent in liquid form which reduces the polystyrene foam to a sludge-like material that is safe to ship and greatly reduces its volume of waste.
BACKGROUND OF THE INVENTION
[0002] Polystyrene foam has been used for some time as packing material, insulation material, structural materials and other various uses. Polystyrene foams exhibit many useful qualities in a wide variety of fields. The foams usefulness is based partly on its cost effectiveness, its inherent insulating qualities and the ease with which it may be formed into a great variety of shapes. For instance, the food handling industry has found polystyrene foam packaging to be of great use in the packaging of food products for its consumers. In addition, the building industry has found a large variety of uses for the foam. The chief concern for the various uses of the foam has been the amount of waste that is generated by the use of polystyrene foam products.
[0003] Generally speaking, polystyrene foam has primarily caused great concern because of its lack of biodegradability. The foam by its very nature takes up a great deal of volume per weight, which has caused many individuals to question its overall commercial usefulness when compared to the overall possible detrimental environmental impact. The environmental impact includes the accelerated rate that landfill space is being used up at because the foam, in its useful form, takes a large amount of space per weight of waste. Moreover, the transportation of the foam waste is very inefficient due to the volume weight ratio. Typically, the waste material is transported from a restaurant facility to a waste area. This transportation usually involves motor vehicle transport. The vehicles can transport a much greater weight of refuse than can be placed in the vehicle due to the large volume the polystyrene foam takes up. Therefore, the transportation of polystyrene foam products in general is very inefficient because the full capacity of the shipping means is not utilized.
[0004] Also, in the industry it has been very difficult to find an effective method of recycling the polystyrene foam products. This is due in part to the shipping cost described above and the cost of the process of the actual recycling. There is a therefore a continued need for a polystyrene foam volume reduction method to allow use of more conventional plastic recycling and processing equipment. At the present, very expensive and specialized processing equipment and extra polystyrene foam compaction steps are required to recycle polystyrene foam products.
[0005] One approach to the recycling of polystyrene foam is to use chemicals to reduce the foam. The basic problem in the industry, however, is that the chemicals that are often considered the most obvious to use are very toxic to the environment with the result that they are often banned by environmental legislation or regulations. One chemical series, pinene and terpenes such as d-limonene can reduce the foam volume. This approach is interesting but unfortunately it fails to be an effective method in some cases. Specifically, the cost of d-limonene is directly related to the crop levels of citrus products. Accordingly, when there is a problem with the production of citrus-based products due to bad growing conditions, it directly effects the price to recycle foam products to the point where it may no longer be cost effective.
[0006] Moreover, prior approaches evidence an inconsistent activity in collapsing polystyrene foams that has not previously been addressed in the industry. For example, while heat activation of the terpenes has removed this problem (U.S. Pat. No. 5,223,543, the entire contents of which are incorporated herein by reference), it adds to the overall cost of recycling and it involves a volatile environmentally compromising chemical. The chemicals used in the '543 patent were problematic for shipping due to their flash point. They are highly volatile and therefore extra precautions have to be taken when shipping such products that ultimately make use of such chemicals cost-ineffective. Moreover, the process used in the '543 patent was basically vapor phase, providing for possible emissions of vapors which were a Clean Air Act Problem. Thus there continues to be a major need for a polystyrene foam reduction process that uses low volatility agents.
[0007] Also, the use of volatile chemicals presents another problem for the recycling efforts of polystyrene foam products. The chemicals used heretofore suffer great loss in the recycling process due to evaporation. This makes the recycling materials vary hard to recover to be used again in the recycling process. As such, it greatly increases the cost to the recycling efforts. The evaporated chemicals would also potentially increase the danger of an accident during the recycling process due to unacceptable flash points of the chemicals. This is especially true were the best performance of the chemicals is aided by the application of heat to the recycling process. Ultimately, the volatile chemicals and heat required lead to conditions during the recycling process that are potentially very dangerous.
[0008] An ideal process would have little need for the heat activation step of U.S. Pat. No. 5,223,543 and would further allow viscous and higher boiling point materials to be employed. Ideally, these materials would not require longer residence times prior to recycling. A long time would delay the sequence of breaking down the polystyrene foam products and shipping of same. This increase in residence times adds to the overall cost of the recycling process. Also, the need to decrease residence time must be balanced with reduced heat activation in combination with higher boiling point materials whose combination would result in a heretofore unobtainable efficient and safe chemical reactant. In addition, it would be most desirable to have the product or sludge of the polystyrene foam collapsing reactions safely shippable. It would also be advantageous to identify effective compounds that insulate the polystyrene foam reducer market from the wide price variation of the orange crop related d-limonene market.
[0009] Also, it would be desirable to have a compound that is environmentally friendly. Part of the major problem with the past use of foam products is that they now occupy a great deal of space in our landfills. Therefore, there is a significant need for an agent that can be used at these landfills on foam, which has already been deposited into landfills. The only way to accomplish this is by the application of a foam reducing agent that has no detrimental side effects on the environment.
[0010] In a prior effort to address some of these needs, Katz et al. were recently issued U.S. Pat. No. 6,743,828 which is directed to a polystyrene foam reduction agent consisting of dibasic esters and a process using a liquid contact with polystyrene foam wherein the higher boiling temperature of the dibasic esters and contact with the liquid provides a volume reduction process and less evaporation loss as well as safer transportation of the chemicals and the polystyrene in its reduced state. The foam reduction agent consisting of dibasic esters and the process employed results in a reduced sludge that is also recyclable to superior quality raw polystyrene foam beads and the reduction agents are recoverable for future use.
[0011] Notwithstanding the usefulness of the prior polystyrene foam reduction recycling systems using dibasic or dialkyl esters, there is a continuing need in the art to develop other more versatile polystyrene foam reduction recycling systems to enhance the efficiency and full range of recycling possibilities. This invention solves these and other long felt needs by providing compositions and methods utilizing low vapor pressure dibasic esters or functional derivatives thereof in a polystyrene foam reduction recycling system.
SUMMARY OF THE INVENTION
[0012] In general, the present invention is directed to novel polystyrene foam reduction recycling compositions and methods that solve the volume problem of recycling polystyrene foam materials while simultaneously allowing the easy and inexpensive shipment of the foamed materials after reduction in volume by use of a novel low vapor pressure dibasic ester composition (hereinafter, LVP-DBE). The methods of the present invention are applicable to all types of expanded or foamed polysyrene materials known to those of skill in the art.
[0013] In one aspect, the present invention provides a novel polystyrene foam reduction recycling system comprising a composition of LVP-DBE comprising dimethyl glutarate [CAS # 1119-40-0] and dimethyl adipate [CAS# 627-93-0]. In one embodiment, the novel polystyrene foam reduction recycling system of the present invention further comprises a composition of LVP-DBE comprising dimethyl glutarate [CAS # 1119-40-0], dimethyl adipate [CAS# 627-93-0] and dimethyl succinate (CAS# 106-65-0), wherein the weight percentage of dimethyl succinate is 1% and less. For example, and not by way of limitation, 1.0%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, and any numerical values there between are specifically permitted for use in the polystyrene foam reduction recycling system of the present invention. Other LVP-DBE-based compositions that may be used in the novel polystyrene foam reduction recycling system of the present invention include LVP-DBE-2, LVP-DBE-3, LVP-DBE-5, LVP-DBE-6, and LVP-DBE-1B as specifically set forth in Table 1.
[0014] Specifically excluded within the scope of the polystyrene foam reduction recycling system of the present invention is the use of non-low vapor pressure DBE. Also specifically excluded within the scope of the polystyrene foam reduction recycling system of the present invention is the use of DBE, DBE-4, and DBE-9 as specifically set forth in Table 1. Also specifically excluded within the scope of the polystyrene foam reduction recycling system of the present invention is the use of dimethyl succinate (CAS# 106-65-0) in weight percentage amounts greater than 1%.
[0015] In one embodiment, the percentage of dimethyl glutarate in the LVP-DBE composition of the present invention is in the range of between about 5% and about 98% weight percent. In one embodiment, the percentage of dimethyl adipate in the LVP-DBE composition of the present invention is in the range of between about 20% and about 98.5% weight percent. In one embodiment, the percentage weight of total diesters in the LVP-DBE composition of the present invention is at least 98.5% weight percent, with an average weight percentage of approximately 99.4-99.7%. It is intended herein that the ranges recited also include all those specific percentage amounts between the recited range. For example, the range of about 20 to 98.5% also encompasses 21 to 97.5% weight percent, 22 to 98.5% weight percent, 21 to 96.5% weight percent, etc., without actually reciting each specific range therewith. In another embodiment, the percentage of dimethyl glutarate in the LVP-DBE composition of the present invention is in the range of between about 2% and about 40% weight percent and the percentage of dimethyl adipate in the LVP-DBE composition of the present invention is in the range of between about 10% and about 50% weight percent.
[0016] In yet another aspect, the present invention provides a novel polystyrene foam reduction recycling system comprising a composition of LVP-DBE that exhibits a significantly lower vapor pressure than standard DBE. In one embodiment, the lower vapor pressure exhibited by the LVP-DBE composition of the present invention is in the range of between about 0.01 to about 0.001 mm Hg@ 20° C. (68° F.), compared to the vapor pressure of standard DBE which is in the range of between about 0.10 to about 0.02 mm Hg@ 20° C. (68° F.). Such lower vapor pressure is important because it translates into a healthier work environment and a lower inhalation risk for potential users and recyclers. The lower vapor pressure also minimizes any apparent odor in the work area for users and recyclers.
[0017] In yet another aspect, the present invention provides a novel polystyrene foam reduction recycling system comprising a composition of LVP-DBE that exhibits a significantly lower vapor pressure than standard DBE, which LVP-DBE meets the low vapor pressure criteria established by the California Air Resources Board for volatile organic compounds in consumer products per California Code of Regulations, Title 17, Division 3, Chapter 1, Subchapter 8.5, Article 2, Section 94508(a) 80(A), the entire contents of which are incorporated herein by reference.
[0018] In yet another aspect, the present invention provides a novel polystyrene foam reduction recycling system comprising a composition of LVP-DBE that exhibits a significantly lower vapor pressure than standard DBE, which LVP-DBE meets the exemption criteria for consumer products per EPA 40CFR59.203(f)1, the entire contents of which are incorporated herein by reference.
[0019] In one embodiment, the novel polystyrene foam reduction recycling system of the present invention further comprises a two component composition of LVP-DBE that provides simplified distillation or other recycling methods.
[0020] In yet another embodiment, the novel polystyrene foam reduction recycling system of the present invention comprises a three component composition of LVP-DBE in which the distillation range of the solvent used to reduce the polystyrene or EPS is unexpectedly narrower than that found in U.S. Pat. No. 6,743,828. Such narrower distillation ranges result in lower equipment costs, better control and lower production and use costs. In one embodiment, the distillation range of the solvent of the LVP-DBE composition of the present invention is in the range of between about 210 to about 225° C. (about 410 to about 437° F.), compared to the distillation range of the solvent of standard DBE which is in the range of between about 196 to about 225° C. (about 385 to about 437° F.). The unexpectedly narrower distillation range of the solvent of the LVP-DBE composition serves to narrow down the boiling range by over 9%. Thus, the range can now be narrowed to reflect the closer boiling point which will result in a better polystyrene bead. By use of a higher heat ratio in the LVP-DBE polygel, breakdown of the LVP-DBE will not occur as easily.
[0021] In yet another aspect, the present invention provides a novel polystyrene foam reduction recycling system comprising a LVP-DBE composition that is chemically more stable than standard DBE. Since the vapor pressure of the LVP-DBE is lower, the polystyrene product is more stable and has certain properties that make LVP-DBE a better choice to use in a given work place. For example, in one embodiment, the LVP-DBE composition will not remove paint or adhesives as quickly as standard DBE.
[0022] In yet another aspect, the present invention provides a novel polystyrene foam reduction recycling system comprising a LVP-DBE composition that is incompatible or can react with, inter alia, strong oxidizers, acids, alkalies, etc.
[0023] In yet another aspect, the present invention provides a novel polystyrene foam reduction recycling system comprising a LVP-DBE composition that will not undergo polymerization.
[0024] In yet another aspect, the present invention provides a novel polystyrene foam reduction recycling system comprising a LVP-DBE composition that reduces foamed polystyrene at a rate of action that equals or exceeds that of standard DBE. Thus, in one embodiment, in outdoor conditions when the temperature is warm, the lower vapor pressure DBE will not evaporate as quickly and therefore will be more effective in reducing expanded polystyrene foam (EPS).
[0025] In yet another aspect, the present invention provides a novel polystyrene foam reduction recycling system comprising a LVP-DBE composition that exhibits a greater holding capacity than standard DBE. In one embodiment, such greater holding capacity at ambient temperature approaches approximately 55%—approximately 75% of polystyrene with the remainder being solvent (LVP-DBE), whereas the holding capacity for a polystyrene foam reduction recycling system using standard DBE approaches approximately 0-50%. Such greater holding capacity is demonstrated by virtue of the lower viscosity of the solution at equal concentrations. This lower viscosity leads to a more cost effective use of the solvent as a more concentrated polygel can be produced which makes recycling of polystyrene foam more effective.
[0026] In yet another aspect, the present invention provides a novel polystyrene foam reduction recycling system comprising a LVP-DBE composition that exhibits a higher flash point than standard DBE. In one embodiment, the flash point of the LVP-DBE composition of the present invention is in the range of between about 102 to about 104° C. (about 216 to about 219° F.), compared to the flash point of standard DBE which is about 100° C. (about 212° F.). Such higher flash points leads to increased safety for the user and recycling process and will minimize transportation restrictions.
[0027] In yet another aspect, the present invention provides a novel polystyrene foam reduction recycling system comprising a LVP-DBE composition that is not regulated as a hazardous material by Department of Transportation (DOT), International Maritime Organization (IMO), or International Air Transport Association (IATA).
[0028] In yet another aspect, the present invention provides a novel polystyrene foam reduction recycling system comprising a LVP-DBE composition for which none of the components present in the LVP-DBE composition are listed by International Agency for Research on Cancer (IARC), National Transportation Program (NTP), Occupational Health and Safety Organization (OSHA) or American Conference of Industrial Hygienists (ACGIH) as a carcinogen
[0029] In yet another aspect, the present invention provides a novel polystyrene foam reduction recycling system comprising a LVP-DBE composition that exhibits biodegradability as measured by the 28-day closed bottle test. The LVP-DBE composition was tested for biodegradability using the 28-day closed bottle test. A minimum of 60% biodegradation must be reached in a 14 day window after exceeding the 10% level in order to pass this test and be rated as readily biodegradable. All of the components of the recycling system of the present invention pass this test and, therefore, DBE-LVP is considered readily biodegradable. In one embodiment, the biodegradability of the dimethyl glutrate in the LVP-DBE composition of the present invention is in the range of between about 70% at day 7 and about 84% at day 14%. In one embodiment, the biodegradability of the percentage of dimethyl adipate in the LVP-DBE composition of the present invention is in the range of between about 58% at day 7 and about 84% at day 14. In one embodiment, the biodegradability of the dimethyl succinate in the LVP-DBE composition of the present invention is in the range of between about 80% at day 7 and about 90% at day 22.
[0030] In yet another aspect, the present invention provides a novel polystyrene foam reduction recycling system comprising a LVP-DBE composition that exhibits one or more of the following characteristics: (a) a significantly lower vapor pressure than standard DBE, (b) the distillation range of the solvent is narrower, (c) chemically more stable than standard DBE, (d) that is incompatible or can react with, inter alia, strong oxidizers, acids, alkalies, etc., (e) that will not undergo polymerization, (f) that reduces foamed polystyrene at a rate of action that equals or exceeds that of standard DBE, (g) that exhibits a greater holding capacity than standard DBE, (h) that exhibits a higher flash point than standard DBE, (i) that is not regulated as a hazardous material by DOT, IMO, or IATA, and (j) for which none of the components present in the LVP-DBE composition are listed by IARC, NTP, OSHA or ACGIH as a carcinogen.
[0031] In yet another aspect, the invention relates, in part, to a novel polystyrene foam reduction recycling system comprising exposing said foams to liquid sprays of specific esters exhibiting one or more of the aforementioned characteristics.
[0032] In yet another aspect, the invention relates, in part, to a novel polystyrene foam reduction recycling system comprising exposing said foams to liquid sprays of specific esters comprising dimethyl glutarate [CAS # 1119-40-0] and dimethyl adipate [CAS# 627-93-0], wherein the ester specifically excludes dimethyl succinate in weight percentage amounts greater than 1%, and wherein said esters exhibit one or more of the aforementioned characteristics.
[0033] In yet another aspect, the invention relates, in part, to a novel polystyrene foam reduction recycling system comprising exposing said foams to liquid sprays of specific esters, wherein the ester is selected from the group consisting of dimethyl glutarate [CAS # 1119-40-0] and dimethyl adipate [CAS# 627-93-0], wherein the esters specifically exclude dimethyl succinate in weight percentage amounts greater than 1%, and wherein said esters exhibit one or more of the aforementioned characteristics.
[0034] In yet another aspect, the invention relates, in part, to the novel use of LVP-DBE for polystyrene reduction that can be more effective if mixed with isopronol or terpenes such as, for example, and not by way of limitation d-limonene.
[0035] In yet another aspect, the invention relates, in part, to a novel polystyrene foam reduction recycling system comprising the steps of (a) exposing polystyrene foam in a container to a solution of specific esters comprising dimethyl glutrate [CAS # 1119-40-0] and dimethyl adipate [CAS# 627-93-0], wherein the esters specifically exclude dimethyl succinate in weight percentage amounts greater than 1%; (b) covering said container; and (c) supplementing polystyrene foam until maximum reduction is achieved.
[0036] In one embodiment, the polystyrene foam may be shredded or grinded prior to exposure to the aforementioned specific ester combination using any mechanical apparatus known to those of skill in the art for shredding or grinding polystyrene foam. By converting the polystyrene foam into smaller fragments, a greater surface area for exposure to the specific ester combination is provided thereby affording faster polystyrene foam reduction.
[0037] In another embodiment, the polystyrene foam may be shredded or grinded prior to exposure to the specific esters combination using any mechanical apparatus and the specific ester combination is then applied using a solvent spraying unit physically connected to the mechanical apparatus. In this embodiment, a container may be placed under the apparatus to collect the reduced sprayed polystyrene foam.
[0038] In yet another embodiment, the polystyrene foam may be shredded or grinded prior to exposure to the specific esters combination using any mechanical apparatus and the specific ester combination is then applied using a hand held solvent spraying unit.
[0039] In yet another aspect, the LVP-DBE composition of the present invention is useful for rendering organic polymeric coatings and finishes such as paints, varnishes, lacquers, shellacs, gums, natural and synthetic resins removable from a wide range of coatings and surfaces such as, for example, and not by way of limitation, wood, metal, and plastic. An important feature of the composition is that it provides excellent results without the need of evaporation retardants or film-forming compounds. Thus, there is no need to include in the formulation such evaporation retardants as paraffin wax or the like, which have the disadvantage that they need to be removed in subsequent processing steps. Another feature of the composition of the present invention is that it has a shelf life in excess of about one year to about 10 years.
[0040] Thus, in yet another aspect, the invention relates, in part, to the novel use of the LVP-DBE composition of the present invention as a paint stripper.
[0041] In yet another aspect, the invention relates, in part, to the novel use of the LVP-DBE composition of the present invention as a graffiti remover.
[0042] In yet another aspect, the invention relates, in part, to the novel use of the LVP-DBE composition of the present invention as a water proofing agent that may be applied via spray means or brush on means.
[0043] In yet another aspect, the invention relates, in part, to the novel use of the LVP-DBE composition of the present invention for removing paints, inks, grease, and the like from skin.
[0044] In yet another aspect, the invention relates, in part, to the novel use of the LVP-DBE composition of the present invention as an extender of the life of concrete by mixing in a minimum of 1.5% of the composition (the reduced polystyrene) but not to exceed 27.5% of the composition.
[0045] In yet another aspect, the invention relates, in part, to the novel use of the LVP-DBE composition of the present invention as an adhesive remover.
[0046] In yet another aspect, the invention relates, in part, to the novel use of the LVP-DBE composition of the present invention as a tar remover.
[0047] In yet another aspect, the invention relates, in part, to the novel use of the LVP-DBE composition of the present invention as a stain remover.
[0048] In yet another aspect, the invention relates, in part, to the novel use of the LVP-DBE composition of the present invention as a scuff mark remover.
[0049] In yet another aspect, the invention relates, in part, to the novel use of the LVP-DBE composition of the present invention as a general degreaser.
[0050] Other preferred embodiments of the invention will be apparent to one of ordinary skill in the art in light of what is known in the art, in light of the following drawings and description of the invention, and in light of the claims.
BRIEF DESCRIPTION OF THE DRAWINGS/FIGURES
[0051] There are no drawings for this application.
DETAILED DESCRIPTION OF THE INVENTION
[0052] This invention reveals a method to provide rapid destruction of the cells of polystyrene foams by use of a combination of specific chemicals of the class of aliphatic dibasic esters, either alone or with other foam reduction agents and surfactants that are active and which readily attack, with no or little heat activation, polystyrene foam and allows easy recycling. The easy recycling is due to reduced bulk and ease of storage of the collapsed polystyrene foam in sludge foam, ease of processing, and economical transportation prior to recycling. The collapsed polystyrene foam may be easily and safely transported.
[0053] The method of the present invention involves the exposure of said foams to liquid sprays of specific esters comprising LVP-DBEs that exhibit one or more of the following characteristics: (a) a significantly lower vapor pressure than standard DBE, (b) the distillation range of the solvent is narrower, (c) chemically more stable than standard DBE, (d) that is incompatible or can react with, inter alia, strong oxidizers, acids, alkalies, etc., (e) that will not undergo polymerization, (f) that reduces foamed polystyrene at a rate of action that equals or exceeds that of standard DBE, (g) that exhibits a greater holding capacity than standard DBE, (h) that exhibits a higher flash point than standard DBE, (i) that is not regulated as a hazardous material by DOT, IMO, or IATA, and (O) for which none of the components present in the LVP-DBE composition are listed by IARC, NTP, OSHA or ACGIH as a carcinogen. Examples of DBE dibasic esters are known to those of skill in the art and include for example, and not by way of limitation, those listed in Table 1 infra.
[0054] In addition to the aforementioned list of properties for the LVP-DBE composition of the present invention, the specific properties of each of the LVP-DBE-2, LVP-DBE-3, LVP-DBE-5, LVP-DBE-6, and LVP-DBE-1B DBE Dibasic Ester compositions as specifically set forth in Table 1 infra are also included as if specifically set forth herein, including for example, and not by way of limitation, ester content (wt. %, min.), water content (wt. %, max.), acid number, mg KOH/g, max., color, APHA, max., turbidity, max., methanol, wt %, isobutanol, wt %, molecular weight, specific gravity at 20/20° C., density at 20° C. (lb/gal), distillation range, ° C., vapor pressure at 20° C. (mm Hg), solubility in water, wt % at 20° C., water solubility in DBE, wt % at 20° C., freezing point, ° C., flashpoint, Tag closed cup, ° C., auto ignition temperature, ° C., latent heat of vaporization, cal/g, viscosity at 25° C., cst, and properties of the solvent including, for example, and not by way of limitation, non-polar, polar, hydrogen bonding, surface tension at 20° C., dynes/cm, and electrical resistance at 24° C., Meg Ohms.
[0055] The above-listed characteristics, as well as any other characteristics provided in Table 1 infra, confer superior and unexpected results, properties, and advantages to the LVP-DBE composition for its use in the polystyrene foam reduction recycling system of the present invention compared to the standard DBE composition as used in U.S. Pat. No. 6,743,828. The aforementioned features and benefits of using the LVP-DBE composition of the present invention translate into a stronger commitment for more responsible stewardship of the environment and provide an excellent example of the concept of closed-loop recycling.
TABLE 1 DBE Dibasic Esters DBE DBE-2 DBE-3 DBE-4 DBE-5 DBE-6 DBE-9 DBE-IB Specification Ester content, 99.0 99.0 99.0 98.5 99.0 99.0 99.0 98.5 wt. %, min. Water content, 0.10 0.10 0.20 0.04 0.10 0.05 0.10 0.1 wt. %, max. Acid number, mg 0.30 1.00 1.00 0.50 0.50 1.00 0.50 1.00 KOH/g, max. Dimethyl 10-25 20-28 85-95 0.1 0.2 max. 98.5 min. 0.3 10-20 f adipate, wt % max. max. Dimethyl 55-65 72-78 5-15 0.4 98.0 max. 1.0 max. 65-69 55-70 f glutarate, wt % max. Dimethyl 15-25 1.0 1.0 max. 98.0 1.0 max. 0.15 max. 31-35 20-30 f succinate, wt % max. max. Color, APHA, max 15 max. 15 max. 15 max. 15 max. 15 max. 15 max. 15 max. 15 max. Turbidity, max. 5 max. 5 max. 5 max. 5 max. 5 max. 5 max. 5 max. 5 max. Typical Composition Ester content, 99.5 99.5 99.5 99.5 99.5 99.0 99.0 99.5 wt. %, min. Dimethyl 21 24 89 — 0.1 99 0.2 21 f adipate, wt % Dimethyl 59 75 10 0.3 99 <0.5 66 59 f glutarate, wt % Dimethyl 20 0.3 0.2 98 0.4 <0.1 33 20 f succinate, wt % Methanol, wt % 0.20 <0.1 <0.1 <0.1 <0.1 <0.1 <0.1 N/A Isobutanol, wt % N/A N/A N/A N/A N/A N/A N/A 0.2 Water, wt % 0.05 0.02 0.04 0.02 0.03 0.03 0.04 0.05 Physical Properties (typical values) Molecular Weight 159 a 163 a 173 a 146 160 174 156 a 242 Specific gravity at 1.092 c 1.081 c 1.068 c 1.121 1.091 1.064 1.099 c 0.958-0.960 20/20° Specification Density at 20° C. 9.09 c 9.00 c 8.89 c 9.33 9.08 8.86 9.18 c 7.97 c (lb/gal) Distillation 196-225 210-225 215-225 196 210-215 227-230 196-215 275-295 Range, ° C. Vapor Pressure at 0.20 c 0.04 c 0.02 c 0.13 0.05 0.01 0.07 c <0.01 c 20° C. (mm Hg) Solubility in water, 5.3 4.2 2.5 7.5 4.3 2.1 ca. 5 <0.1 wt % at 20° C. Water Solubility in 3.1 2.9 2.5 3.8 3.2 2.4 ca. 3.5 0.6 DBE, wt % at 20° C. Freezing Point, ° C. −20 c −13 c 8 c 19 −37 10 −10 c −55 Flashpoint, Tag 100 104 102 94 107 113 94 133 closed cup ° C. Physical Properties (typical values) Auto ignition 370 375 360 365 365 360 365 >370 temp., ° C. Latent heat of 81 80 79 85 81 79 82 N/A vaporization, cal/g Viscosity at 25° C., 2.4 2.5 2.5 2.5 2.5 2.5 2.4 18.8 cst Solvent Properties non-polar d 8.3 8.3 8.3 8.3 8.3 8.3 8.3 7.9 polar d 2.3 2.2 2.1 2.5 2.3 2.1 2.3 1.3 hydrogen bonding d 4.8 4.7 4.5 5.0 4.8 4.5 4.8 3.6 Surface tension 3.56 N/A N/A N/A N/A N/A N/A 27.2 at 20° C., dynes/cm Electrical 0.5 N/A N/A N/A N/A N/A N/A N/A Resistance e at 24° C., Meg Ohms a Average for mixture b Äsp. Gr./ÄT = −0.0007 per ° C. over the range 20-50° C. c Approximate, based on composition d Hansen Solubility Theory e Ransberg Paint Resistance Tester Model 219CB f Di-Isobutylester
[0056] In one embodiment, terpenes, isopropanols can be added and the addition of any from the family of non-ionic surfactants will serve to raise the flash point. A representative example of a non-ionic surfactant would be NP 9 or the terpenes such as d-limonene, etc. Other foam reducing agents such as esters from celery, or other vegetables such as soybean, etc., or for example, olive oil, will work but prove to be inefficient on their own. In another embodiment, some of the above esters do not have a low flash point or have higher vapor pressure working in combination with LVP-DBE but will work in combination just as fast and in some case even at faster rates of reduction. In short, the addition of surfactants serves to help raise the boiling point of other solvents. All of the other compositions in the terpenes and isopropanols family have lower boiling points compared to both standard DBE and or LVP-DBE.
[0057] The term “surfactant” is used following the nomenclature system of the International Cosmetic Ingredient Dictionary, 5.sup.th ed., J. A. Wenninger et al. eds., The Cosmetic, Toiletry, and Fragrance Association, Washington, D.C. (1993), usually followed by a chemical name and a trademark name of a particular product. Other non-limiting examples of surfactants useful in the compositions and methods of the present invention are isotridecyl alcohol tri-ethoxylate (Surfonic.RTM. TDA-3B, Huntsman Corp.), C.sub.9-C.sub.11 pareth-6 [polyethylene glycol ether of mixed synthetic C.sub.9-C.sub.11 fatty alcohols having an average of 6 moles of ethoxalate; Neodol.RTM. 91.6], C.sub.11-C.sub.15 pareth-59 [polyethylene glycol ether of mixed synthetic C.sub.11-C.sub.15 fatty alcohols having an average of 59 moles of ethoxalate; Tergitol.RTM. 15-S-59], nonoxynol-6 [polyethylene glycol (6) nonylphenyl ether; Tergitol.RTM. NP-6], nonoxynol-9 [polyethylene glycol (9) nonylphenyl ether; Tergitol.RTM. NP-9], and a modified alkanolamide alkanolamine [Monamine.RTM. 1255], as well as other surfactants known to those of skill in the art.
[0058] This invention solves the volume problem of polystyrene foam materials and allows the easy and inexpensive shipment of the foam materials after cost effective reduction in volume by use of certain liquid aliphatic dibasic esters. The materials used in the LVP-DBE composition comprise dimethyl glutarate, dimethyl adipate and dimethyl succinate (with the proviso that the dimethyl succinate is in weight percentage amounts of 1% and less), which are effective foam reduction agents. While they have activity individually, as mixtures of dimethyl glutarate and dimethyl adipate with dimethyl succinate in weight percentage amounts of 1% and less, the action is especially favorable. Moreover, with the addition of small amounts of heat to the process, the overall effectiveness of the LVP-DBE composition is increased while having little effect on the cost of recycling. In particular, when heat is added to the process the speed of reduction of the polystyrene foam or expanded polystyrene (EPS) is increased. The heat can be introduced by several methods, for example, and not by way of limitation, heating the mixture by use of a drum heater or an inline heating element delivering the LVP-DBE or LVP-DBE mixture will dramatically the increase rate of reduction by up to three (3) to five (5)-fold but not to exceed twenty fold. Also, because of the lower boiling points of the individual reactants, very little reactant is lost in the heating process. The lower boiling points and benign nature of the reactants makes the reactant process safer than previously known and commercially used chemical reactants with higher boiling points.
[0059] The use of the aforementioned active LVP-DBEs assist in making the expanded or foamed polystyrene materials easier to reduce, collapse and/or reprocess. The polystyrene foam bead or pumpable polygel product of this process is solvatable. The polystyrene foam bead product can also be made pumpable and can then be filtered and reprocessed or injected into furnaces where the high fuel value of the material offers considerable energy savings for users and/or recyclers. If filtered and recycled, high quality polystyrene raw material bead product can be made. In particular, both the standard DBE and LVP-DBE produce high quality beads. This is a function of the Styro Solve recycling system previously implemented by Katz et al., the contents of which are specifically incorporated by reference in their entirety. By using the LVP-DBE of the present invention, the polygel so produced and transported to the plant has proven to be more consistent than that produced using standard DBE. Since the LVP-DBE used in the methods of the present invention has a lower vapor pressure, it is noted that less evaporation occurs on route to the processing plant and hence one receives a more constant polygel product. This also translates into less solvent being used in the polystyrene reprocessing center. Moreover, by using less solvent to produce the correct viscosity for recycling, one also reduces the time and energy required in the process. This results in a more cost effective and cost efficient polystyrene foam recycling process.
[0060] Heretofore, it has been impossible to cost effectively recycle polystyrene high quality raw post consumer material. High quality recycling is important in polystyrene recycling where the recycled product is desirable to be used in the food packing industry. The food packing industry has strict requirements for parts per million of contaminants in the polystyrene used, the contents of which are specifically incorporated by reference in their entirety. The process disclosed herein is the only known recycling process that is both cost effective and yields recycled material that meets the requirements of the food packing industry while still satisfying the low vapor pressure criteria established by the California Air Resources Board for volatile organic compounds in consumer products per California Code of Regulations, Title 17, Division 3, Chapter 1, Subchapter 8.5, Article 2, Section 94508(a) 80(A) and meets the exemption criteria for consumer products per EPA 40CFR59.203(f)1, the entire contents of which are incorporated herein by reference.
[0061] Furthermore, the process of volume reduction of polystyrene foam has been previously hampered by high loss due to evaporation. The use of the novel composition of the present invention helps cure this problem by employing polystyrene foam reduction agents comprising LVP-DBEs that exhibit one or more of the following characteristics: (a) a significantly lower vapor pressure than standard DBE, (b) the distillation range of the solvent is narrower, (c) chemically more stable than standard DBE, (d) that is incompatible or can react with, inter alia, strong oxidizers, acids, alkalies, etc., (e) that will not undergo polymerization, (f) that reduces foamed or expanded polystyrene at a rate of action that equals or exceeds that of standard DBE, (g) that exhibits a greater holding capacity than standard DBE, (h) that exhibits a higher flash point than standard DBE, (i) that has a relatively low odor compared to standard DBE; (j) that is not regulated as a hazardous material by DOT, IMO, or IATA, and (k) for which none of the components present in the LVP-DBE composition are listed by IARC, NTP, OSHA or ACGIH as a carcinogen.
[0062] The materials used in this method of polystyrene foam volume reduction are also recoverable by removal in the recycling process and the majority of compounds used can be easily separated from moisture and volatile organics by a combination of decanting, mutual solubility with other organic compounds and thermal stripping. The materials are further environmentally non-toxic.
[0063] The development of this invention began with identification of the unexpected affinity of the vapors of certain solvents found in perfumes. Identification of the active agent in the process became the key to the initial polystyrene foam volume reduction process. This material identified was d-limonene. D-limonene vapors acted upon the polystyrene foam and rapidly reduced the volume. The sorption process, when there was sufficient vapor present, was one that continued until the polystyrene foam was reduced to a viscous liquid. This aggressive mutual solubility was relatively fast as long as there is a presence of the needed vapors.
[0064] This invention furthers the concept of foam reduction by the further discovery of a set of chemicals which are as effective as the vapor process noted with d-limonene but which work in a liquid state and thus avoids the need for a vapor saturated atmosphere around the collapsing foam. The inventor's prior work focused on the combined use of non-low vapor pressure dimethyl glutarate and dimethyl adipate, and dimethyl succinate (CAS# 119-40-0; CAS# 627-93-0; CAS# 106-65-0, respectively) which are effective polystyrene foam reduction agents. The present invention furthers this prior discovery in that only LVP-DBEs are employed as effective polystyrene foam reduction agents. The use of dimethyl succinate (CAS# 106-65-0) in weight percentage amounts greater than 1% is specifically excluded from the scope of this invention.
[0065] This invention discloses the new combination of chemicals that have not previously been considered for this purpose since they are not easy to use in the vapor phase. This new low vapor pressure dibasic ester combination of dimethyl glutarate and dimethyl adipate with dimethyl succinate present in weight percentage amounts of 1% and less eliminates much of the loss of the LVP-DBE reagents and further improves fire safety of the recycling or foam reduction process. The extra factor is the removal of the vapor requirement with discovery of liquid phase foam reduction agents. Importantly, by lowering the vapor pressure and lowering the loss of the LVP-DBE, the final stage of the reprocessing (recycling) is completed in a much more efficient manner. More importantly, this new method of recycling polystyrene foam using LVP-DBE now falls under the new California Code of Regulations, Title 17, Division 3, Chapter 1, Subchapter 8.5, Article 2, Section 94508 (a) 80(A) vapor-pressure EPA standards, the entire contents of which are incorporated herein by reference, thereby allowing the product to be used whereas the current standard DBE can not. Also, as noted supra, use of the LVP-DBE allows the polygel to be more safely transported to the recycling plant since there is less vapor pressure and thus, less evaporation of the LVP-DBE.
[0066] The formulas used for this invention consist of esters, specifically dibasic esters. These esters, especially the aliphatic dibasic esters such as dimethyl glutarate and dimethyl adipate (CAS# 119-40-0 and CAS# 627-93-0, respectively) have rapid reaction with polystyrene foams (both foamed and expanded), again acting as a stress cracking agent to destroy the cell wall webs which are highly stressed, then destroying the intercellular structure that remains. In addition, through experimentation that is the subject of the invention disclosed herein it was learned that the esters themselves were effective reactants when small amounts of heat were added to the process. Esters have been disclosed in a U.S. patent to Shiino et al. U.S. Pat. No. 5,629,352. However, that disclosure does not teach nor contemplate heating. The addition of small amounts of heat to the LVP DBE ester composition of the present invention prior to its use as a reactant greatly increases is reactant characteristics. The presence of esters without heat will reduce foam but in a time period that is not efficient for recycling purposes.
[0067] The dibasic or dialkyl esters disclosed herein above are not like the vapor processes used previously for foam reduction, which attack polystyrene foam by dissolving the polystyrene foam in the vapors of natural organic compounds. The present dibasic ester chemicals act as liquids. The dibasic esters have boiling points of 196 to 225° C., with a vapor pressure of only 0.2 mm Hg at 20° C. while the vapor pressure for LVP-DBE is only 0.02 Hg@ 20° C. They have an evaporation rate one tenth that of butyl acetate (Vapor pressure: 8 mm Hg at 20° C.), a common reference. Should the evaporation read from one fortieth for standard DBE (vapor pressure of 0.2 mm Hg@20° C.) and one four hundredth for LVP-DBE (vapor pressure of 0.02-0.04 mm Hg@ 20° C.). The specific gravity is slightly greater that water and mutual solubility is limited, allowing easy separation from water mixes. The dibasic esters also have low solubility in water and very high solubility in many alcohols so that separation schemes for recovery of the dibasic mix is feasible. The use of the dibasic esters, especially as a mixture, eliminates the large loss due to evaporation of the d-limonene used as the reducing agent in previous polystyrene foam reduction and recovery methods. The evaporation of active agents had previously made the process partly ineffective in many applications because of cost. The present invention is cost effective since this loss is very low.
[0068] The active agents also have several key property requirements or needs. Since the active agents will ultimately be placed into trash and garbage dumps, they must be environmentally safe and sound. Ideally, the active agents should not be within a range of boiling points and vapor pressures that will either immediately flash off or will over time evaporate to form a vapor layer within a landfill. With respect to solvents, which attack polystyrene foams, nearly all solvents are environmental problem chemicals. One class of chemicals broadly noted as isoprenoid and terpene compounds contain mostly environmentally safe naturally derived compounds, but most of these compounds are relatively volatile and would at least form a vapor layer in a landfill dump situation. The dibasic esters of this invention are of sufficiently low volatility that they do not form an indump/landfill vapor layer. This removes future problems of large vapor escape if the dump/landfill top impermeable layers are destroyed or damaged by man made or natural phenomena such as, inter alia, earthquakes.
[0069] In the prior patents on activation (for example, U.S. Pat. No. 5,223,543) the emphasis was on d-limonene. This reduction agent was selected for cost and volatility reasons since prior uses in the field relied on rapid action due to application in exposed areas as activated liquid. The use of a variety of liquid volatilities as long as vapor is generated over an extended time ranging from several hours to several days is also contemplated herein. The present use of esters with small amounts of heat, dibasic esters, and d-limonene in combination with esters and dibasic esters, as foam reduction agents is also effective and is specifically contemplated herein. The present invention is vastly superior compared to the use of standard DBE in creating a vast reduction in the vapor loss, in preventing vapor layers within garbage or landfill disposal dumps, in reduction of loss in reprocessing operations, which are typically at temperatures of over 270° C. Also, the present invention limits reliance on d-limonene, which can experience unstable pricing and is not easily reclaimed after recycling.
[0070] Finally, all of the contemplated reactants described herein may be optionally aided in their reactant effectiveness by including in the reactant process a pretreatment shredding or grinding of the polystyrene. The shredding can be effectively accomplished through the use of a hopper that shreds the polystyrene in the first stage of the process. The second stage of the process would have the shredded polystyrene being treaded with one of the disclosed reactants in a holding compartment of the hopper. The resultant foam sludge could then be pumped from the hopper to containers for transportation to waste or recycling locations.
[0071] In one embodiment, a mixture of a dibasic esters comprising dimethyl glutarate, dimethyl adipate, and dimethyl succinate with the dimethyl succinate being present in weight percentage amounts of 1% and less; and a surfactant, are sprayed onto pre-shredded polystyrene foam waste. In another embodiment, a mixture of a dibasic esters comprising dimethyl glutarate, dimethyl adipate, and dimethyl succinate with the dimethyl succinate being present in weight percentage amounts of 1% and less, are sprayed onto pre-shredded polystyrene foam waste in the absence of a surfactant.
[0072] Examples of foam waste that can be reduced using the compositions and methods of the present invention can be from a variety of sources that include, for example, and not by way of limitation, foam serving plates and containers in a fast food restaurant, the residues of packing for food or industrial objects (representative non-limiting examples of foamed or expanded polystyrene that can be reduced using the methods of the present invention include, inter alia, computer end caps, packaging expanded polystyrene (EPS) peanuts, insulation board, Styrofoam®, construction forms, coffee cups, egg cartons, drink cups, meat trays, vegetable trays, protective packaging, furniture, lamps, lamp shades, paintings, appliances such as refrigerators, stove dish washers, microwave ovens, cameras, VCRs, TVs, telephones, vacuums, radios, chemical packaging military applications for pollution prevention items such as: munitions packaging, target drones, weapons, food service, agriculture; seedling trays, various industries such as tobacco growers, greenhouses (for their seeding trays) plant growers for their planting, fruit and vegetable growers for their shipping containers; foam coolers, fish containers, among others. The foam waste would be shredded in a hopper. The shreds of polystyrene foam would be contained in a compartment of the hopper. The reactant would be sprayed onto the shredded foam waste. The spray and shredded foam combination will rapidly decrease in volume as the foam collapses and would result in the forming of foam sludge and volume of reducing agent. The sludge and reducing agent would be pumped from the hopper compartment into drum type containers and sent to dumps where it occupies a greatly reduced volume or sent to a reprocessor to recover the active agent dibasic esters and the polystyrene polymer. Preferably the reducing agent is ninety percent dibasic ester and not to exceed 10 percent surfactant.
[0073] The process is preferably the same as described above with alternate reactant compositions. However, the embodiments contemplated herein are not limited to the pre shredding of the foam waste, the use of a hopper, the pumping of the foam sludge and reactant or the use of drum-like containers for transporting the foam sludge and reactant. Indeed, the embodiments contemplated herein may be used in conjunction with other processing methods of polystyrene foam waste known to those of skill in the art.
[0074] In a second embodiment, the reactant is at least one of the three named dibasic esters which is combined with d-limonene; and a surfactant, whereby the reactant in a liquid state contacts polystyrene foam causing the collapse of the polystyrene cell to form a compact polystyrene gel material that is easily shippable. Preferably the reactant, or foam reduction agent, is eighty eight weight percent of the dibasic ester, ten percent d-limonene and two percent of the surfactant. In addition, it is preferred that the surfactant is at least one of an industry standard surfactant known as NP5 and NP9. Other non-ionic surfactants know to those of skill in the art can be used in conjunction with the DBE and LVP-DBE compositions of the present invention.
[0075] In a third embodiment, the reactant is a dibasic esters that is at least one of the group of dimethyl glutarate, dimethyl adipate, and dimethyl succinate, with the dimethyl succinate being present in weight percentage amounts of 1% and less; d-limonene; and, a vegetable oil are used as the reducing agent whereby the reactant in a liquid state contacts the polystyrene foam causing the collapse of the polystyrene cell to form a compact polystyrene gel material that is shippable. Preferably, the reactant, or foam reduction agent, is fifty five percent vegetable oil, thirty percent dibasic ester and fifteen percent d-limonene. It is also preferred that the vegetable oil is soy oil. Other examples of preferred oils include, for example, and not by way of limitation, oils from celery and olives.
[0076] All of the embodiments described above are sprayed onto polystyrene foam. The preferred process is to have the polystyrene foam placed into a hopper wherein the foam is converted to small pieces that can be combined with the reducing agent. The resulting material, sludge and reducing agent are pumped from the hopper to drums for transportation. In another aspect, the process involves the use of a novel mechanical device that is to be the subject of another application by the inventors.
EXAMPLES
[0077] It will be understood by one of ordinary skill in the relevant arts that other suitable modifications and adaptations to the methods and applications described herein are readily apparent from the description of the invention contained herein in view of information known to the ordinarily skilled artisan, and may be made without departing from the scope of the invention or any embodiment thereof. Having now described the present invention in detail, the same will be more clearly understood by reference to the following examples, which are included herewith for purposes of illustration only and are not intended to be limiting of the invention.
[0078] The embodiments described herein are not a limitation to invention disclosed by this application but are shown to illustrate the best methods and uses of the invention. Further uses would be obvious to those skilled in the art by a complete review of the disclosure made herein.
Example 1
[0079] Determination of the exposure limits of the LVP-DBE agents used in the novel polystyrene foam reduction recycling system
Exposure Limits
[0000] DBE-LVP
[0000] PEL (OSHA): None Established
[0000] TLV (ACGIH): None Established
[0000] AEL*: 1.5 ppm, 10 mg/m3, 8 Hr. TWA
[0000] *AEL is DuPont Chemical Inc.'s Acceptable Exposure Limit. Where governmentally imposed occupational exposure limits which are lower than the AEL are in effect, such limits shall take precedence.
Example 2
[0080] Determination of the physical and chemical properties of the LVP-DBE agents used in the novel polystyrene foam reduction recycling system
Physical and Chemical Properties
[0000] Odor: Sweet
[0000] Form: Liquid
[0000] Specific Gravity: 1.1@20 C (68)
[0000] Boiling Point: 210-225 C (410-437 F)
[0000] Vapor Pressure: 0.02-0.04 mm Hg@ 20 C (68 F)
[0000] Melting Point: −13 to 8 C (9-46 F)
[0000] % Volatiles: 100 WT %@20 C (68 F)
[0000] Evaporation Rate: <0.1 (Butyl Acetate=1.0)
[0000] Solubility in Water: 2.5-4.2 WT %@20 C (68 F)
Example 3
[0081] Determination of the exposure guidelines of the LVP-DBE agents used in the novel polystyrene foam reduction recycling system
Exposure Guidelines
[0000] Exposure Limits
[0000] DBE-LVP
[0000] PEL (OSHA): None Established
[0000] TLV (ACGIH): None Established
[0000] AEL*: 1.5 ppm, 10 mg/m3, 8 Hr. TWA
[0000] This limit is for DBE.
[0000] *AEL is DuPont's Acceptable Exposure Limit. Where governmentally imposed occupational exposure limits which are lower than the AEL are in effect, such limits shall take precedence.
Example 4
[0082] Determination of the hazardous chemical indicators of the LVP-DBE agents used in the novel polystyrene foam reduction recycling system
Hazardous Chemical Lists
[0000] SARA Extremely Hazardous Substance: No
[0000] CERCLA Hazardous Substance: No
[0000] SARA Toxic Chemical: No
[0000] DBE-LVP is considered 100% VOC (1080 g/l) per EPA 40 C.F.R. Section 51.100(s)1.
[0000] DBE-LVP meets the VOC exemption criteria for consumer products per EPA 40 C.F.R. Section 59.203(f)1.
[0083] DBE-LVP meets the low vapor pressure (LVP) criteria established by the California Air Resources Board for volatile organic compounds in consumer products per California Code of Regulations, Title 17, Division 3, Chapter 1, Subchapter 8.5, Article 2, Section 94508(a)80(A).
Canadian Regulations
[0084] CLASS D Division 2 Subdivision B—Toxic Material. Skin or Eye Irritant.
[0000] Equivalents
[0085] The invention illustratively described herein suitably may be practiced in the absence of any element or elements, limitation or limitations which is not specifically disclosed herein. Thus, for example, in each instance herein any of the terms “comprising,” “consisting essentially of,” and “consisting of” may be replaced with either of the other two terms. The terms and expressions that have been employed are used as terms of description and not of limitation, and there is no intention that in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that although the present invention has been specifically disclosed herein, optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the appended claims. In addition, where features or aspects of the invention are described in terms of Markush groups, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group.
[0086] The invention has been described broadly and generically herein. Each of the narrower species and subgeneric groupings falling within the generic disclosure also form part of the invention. This includes the generic description of the invention with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein. Other aspects of the invention are within the following claims.
[0087] All publications, patents and patent applications mentioned in this specification are indicative of the level of skill of those skilled in the art to which this invention pertains, and are herein incorporated by reference to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference. | The present invention relates to a foam reduction agent comprising low vapor pressure dibasic esters and a method of using a liquid to contact with polystyrene foam wherein the higher boiling temperature of the low vapor pressure dibasic esters and contact with the liquid provides a volume reduction process and less evaporation loss as well as safer transportation of the chemicals and the polystyrene in its reduced state. The resulting reduced sludge is also recyclable to superior quality raw polystyrene foam beads and the reduction agents are recoverable for future use. The resulting sludge also has unexpected beneficial uses heretofore unknown as a waterproofing agent, a paint stripper, as a graffiti remover, as an extender of the life of concrete, as an adhesive remover, as a stain remover, as a scuff mark remover, and as a general degreaser. | 2 |
BACKGROUND OF THE INVENTION
The present invention concerns amino ketone enantiomers and their direct preparation from an enantiomeric precursor using Friedel Crafts catalysis.
Aminoindanols of the formula: ##STR1## where R is H or CH 3 are disclosed in the literature [(see e.g. E. Dornberger, Liebigs Ann. Chem. 743, 42-49 (1971); N. Levin et al., J. Org. Chem. 9, 380-391; R. V. Heinzelmann et al., J. Org. Chem. 14, 907-910; Remik et al., Lieb. Ann. Chem. 725, 116 (1969)]. The formula A compounds have two chiral centers at the 1 and 2 positions. Thus, four enantiomers, comprising two pairs, are possible. The enantiomeric pairs are designated as cis and trans. The Formula A compounds and their enantiomers are indicated to have pharmaceutical activity like ephedrine e.g. as bronchodilators.
Preparation of the A compounds is generally carried out by catalytic reduction of the corresponding ketone of the formula: ##STR2## which yields a mixture of enantiomers. A process has been discovered for direct preparation of a single enantiomer of Formula B which is then converted directly to a single enantiomer of Formula A.
SUMMARY OF THE INVENTION
A process for preparing an enantiomer of an aminoindanol by (1) preparing an enantiomer of an aminoindanone or phenylketone via Friedel Crafts reaction of an N-CO 2 R protected amino acid enantiomer and (2) subsequently reducing the product from (1); the intermediate from (1); and the (1) process step.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
An embodiment of the present invention is a process for preparing an enantiomer of a compound of the formula ##STR3## wherein Z is H or CH 3 wherein ○A is a phenyl or substituted phenyl group and n is 1-3 which comprises, (1) when Z is CH 3 ,
(i) the reaction of an enantiomer of a compound of the formula ##STR4## wherein X is Cl, Br or OH and R is C 1 -C 6 alkyl with a Friedel Crafts catalyst to produce a corresponding enantiomer of a compound of the formula ##STR5## (ii) reducing the formula III compound to obtain the formula I compound wherein Z is CH 3 and (2) when Z is H, additionally hydrolyzing the product from (ii) to obtain the formula I wherein Z is H. An intermediate reduction product obtained in step (2) has the formula ##STR6## By corresponding enantiomer we mean that the optical configuration at the amino center in III has been established and is identical to that present in II.
The four enantiomers of the Formula I or III compounds are designated as 1S, 2S; 1R, 2S, 1R, 2R and 1S, 2R. The isomer pairs 1S, 2R and 1R, 2S are designated cis; the 1S, 2S and 1R, 2R pairs are designated trans.
○A is phenyl or substituted phenyl group. The substituted phenyl group may have 1 or 2 substituents selected from OCH 3 and OH. Examples of substituted phenyl groups are ##STR7## and the like.
Any Friedel Crafts catalyst may be used such as BF 3 , FeCl 3 , AlBr 3 , with the aluminum halides being preferred but AlCl 3 being most preferred. Where R=OH, Polyphosphoric acid (PPA), and related catalysts may be used to give the required intermediate acylium ion.
Reduction may be carried out using any convenient reducing agent system. Thus, reduction may be carried out with LiAlH 4 (LAH), or other metallo organic hydride; with H 2 and catalyst e.g. Pd/H 2 , with BH 3 .THF followed by LiAlH 4 and the like.
Reduction with a hydride reagent yields the trans isomers substantially free of the cis. Catalytic reduction yields a mixture of cis and trans isomer which can be separated by conventional methods. R is C 1 -C 6 alkyl such as CH 3 , n-hexyl, --C(CH 3 ) 3 , ethyl and the like.
A flow sheet illustrating the process follows ##STR8##
The formula I compounds have pharmaceutical utility like epinephrine e.g. as bronchodilators, or adrenergic agents.
Another embodiment of this invention is the step (1) process described above and the formula II intermediate therefrom.
Another embodiment of the present invention is a process for preparing a compound of the formula ##STR9## wherein R is C 1 -C 6 alkyl A is phenyl or substituted phenyl and R 1 is H or C 1 -C 6 alkyl especially CH 3 which comprises coupling of a compound of the formula
○A V
with a compound of the formula ##STR10## where X is Cl, Br or OH in the presence of a Friedel Crafts catalyst.
When R 1 in formula VI is other than H, there is a chiral center at the 2 carbon atom and the compound is optically active. Using an enantiomer of this compound where R 1 is e.g. CH 3 in the aforesaid reaction, an enantiomer of the formula IV compound will be obtained. The optical isomers are designated using conventional symbols such as (-) and (+), D and L, or d and L. The (S) and (R) designations which indicate fixed structural configuration are also used.
The formula IV compound be it racemic or enantiomeric may be reduced to yield (as illustrated by the following equation) the corresponding alkanolamines which have pharmaceutical activity. Reduction would yield a mixture of diastereomers which are subject to separation by conventional techniques. Thus, the use of a pure enantionmer of VI would yield an enantiomer of IV which upon reduction would produce two pure enantiomers diastereomeric to one another which may be separated.
The following examples illustrate processes of the present invention.
EXAMPLE 1
(S)-2-Methoxycarbonylamino-1-indanone (2)
To an ice-cooled solution of L-phenylalanine (16.5 g., 0.1 m) in 1N NaOH (100 ml) to which solid Na 2 CO 3 (5.3 g, 0.05 m) had been added was added to the methyl chloroformate (7.8 ml, 0.1 m). Stirring was continued for 1/2 hr. with cooling and 1/2 hr. without. The mixture was carefully acidified with concentrated HCl to pH 2-3. After extraction with CH 2 Cl 2 and drying (Na 2 SO 4 ), evaporation of the solvent left
(S)-N-methoxycarbonylphenylalanine (1) (21 g, 94%)
To an ice-cooled solution of 1 in ether (300 ml) was added solid PCl 5 (19.4 g, 0.093 m). Stirring was continued for 1 hr. with cooling and 1/2 hr. without. After concentration of the mixture at 30° C./25 tarr, the residue was dissolved in CH 2 Cl 2 (250 ml) and added dropwise rapidly to a suspension of AlCl 3 (37.2 g, 0.28 m, 3 m equiv.) in CH 2 Cl 2 (150 ml). Stirring was continued for 1-2 hr after the addition had been completed. The mixture was poured into ice-cold, dilute HCl with vigorous stirring which was continued for 1 hr. The layers were separated and the aqueous phase was extracted several times with CH 2 Cl 2 . The combined organic phase was dried (Na 2 SO 4 ), filtered through silica gel, and concentrated to give the product 2 (13.2 g, 64% overall); m.p. 157°-159°. A small portion of 2 was recrystallized from toluene; m.p. 164°-166° C.; [Ε] D 25 +134.1°(c=0.51, CHCl 3 );
Analysis: Calculated for C 11 H 11 NO 3 ; 64.38% C; 5.40% H; 6.83% N. Found: 64.33% C; 5.50% H; 6.86% N.
EXAMPLE 2
(R)-2-Methoxycarbonylamino-1-indanone-(3)
Using the same procedure as in Example 1, but replacing L-phenylalanine with D-phenylalanine, the 3 compound [m.p. 162°-163° C.; [α] D 25 -132.05°(C=0.44, CHCl 3 )] was obtained.
Analysis: Calculated: as above. Found: 64.21% C; 5.45% H; 6.91% N.
EXAMPLE 3
Racemic-2-Methoxycarbonylamino-1-indanone (4)
Using the same procedure as in Example 1, with racemic phenylalanine in place of L-phenylalanine, the 4 compound [m.p. 141°-143° C.] was obtained.
Analysis: Calculated: as above. Found: 64.79% C; 5.42% H; 6.82% N.
EXAMPLE 4
(1S, 2S)-2-Methylamino-1-indanol(5)
To lithum aluminum hydride (3.20 g, 0.085 m) in THF (100 ml) was added a suspension of (S)-N-methoxycarbonylamino-1-indanone 2 (8.72 g, 0.0425 m) in THF (100 ml) dropwise over 1/2 hr. The mixture was refluxed for 1/2 hr. and then cooled. A saturated aqueous Na 2 SO 4 solution was added dropwise to quench the excess LAH. After stirring for 1/2 hr., CH 2 Cl 2 was added along with solid Na 2 SO 4 for drying, and the mixture was filtered. Evaporation of the solvent gave the crude product 5 which exhibited the following properties after trituration with hot butyl chloride; m.p. 140°-142° C; [@] D 25 +39.34 (C=0.516, CH 3 OH).
Analysis: Calculated for C 10 H 13 NO; 73.57% C; 8.03% H; 8.59% N Found: 73.29% C; 8.04% H; 8.58% N.
EXAMPLE 5
(S)-2-Methoxycarbonylamino-1-phenylpropanone (7)
To an ice-cooled solution of L-alanine (17.8 g, 0.2 m) in 1N, NaOH (200 ml) to which solid Na 2 CO 3 (10.6 g, 0.1 m) had been added was added methyl chloroformate (15.5 ml, 0.2 m). Stirring was continued for 1/2 hr. with cooling and 1/2 hr. without. The mixture was carefully acidified with conc. HCl to pH 2-3. After extraction with CH 2 CL 2 and drying (Na 2 SO 4 ), concentration of the solvent left (S)-N-methoxycarbonylalamine (6) (4.85 g, 16.5%).
To an ice-cooled solution of 6 in ether (100 ml) was added solid PCl 5 (6.86 g, 0.033 m). Stirring was continued for 1/2 hr. with cooling and 1/2 hr. without. After concentration of the mixture at 30°/25 tarr, the residue was dissolved in CH 2 Cl 2 (20 ml). Stirring was continued for 1-2 hr. after the addition had been completed. The mixture was poured carefully into ice cold dilute HCl with vigourous stirring which was continued for 1/2 hr. The layers were separated and the aqueous phase was extracted once more with CH 2 Cl 2 . The combined organic phase was dried (Na 2 SO 4 ), filtered through silica gel, and concentrated. Flash chromatography of the residue on Silica gel 60 (230-400 mesh) eluting with 5% CH 3 OH/CH 2 Cl 2 provided the product 7 as a yellow oil (3.6 g, 52.7%); [@] D 25 -10.4°(C=0.69, CHCl 3 ). A high resolution mass spectrum was consistent with the proposed structure as was the proton NMR spectrum. Chiral Shift NMR analysis indicated the presence of only 2-3% of the (R)-isomer.
EXAMPLE 6
Racemic-2-Methoxycarbonylamino-1-phenylpropane (8)
Using the same procedure as in Example 5, with racemic alamine in place of L-alanine, the 8 compound [yield=58%] was obtained. A high resolution mass spectrum was consistent with the proposed structure as was the proton NMR spectrum.
EXAMPLE 7 ##STR12##
(1S, 2S)-2-N-Methoxycarbonylamino-1-indanol (9)
To a suspension of (S)-2-N-methoxycarbonylamino-1-indanone (2.05 g. 0.01 m) in THF (25 ml) was added dropwise a solution of borane in THF (1 m, 10 ml, 0.01 m) while cooling in an ice bath. Stirring was continued for 2 hours while the mixture warmed to room temperature. Acetic acid and methanol were carefully added, and the mixture was concentrated on a rotary evaporator. The residue was again treated with methanol and reconcentrated. After pumping on to remove residual solvent, the 9 compound was isolated (1.95 g, 94%). Recrystallization from CHCl 3 gave 9; mp 176°-178° C; [α] D 25 23.62°(C=0.58, CH 3 OH).
EXAMPLE 8
Racemic-2-N-Methoxycarbonylamino-1-indanol (10)
The substitution of racemic 2-N-methoxycarbonylamino-1-indanone for the (S)-isomer in the Example 7 procedure led to the formation of racemic compound 10, m.p.--178°-180° C.
EXAMPLE 9
(1S, 2S)-2-methylamino-1-indanol (5)
The substitution of (1S, 2S)-9 for the starting material [(S)-2] in Example 4 led to the formation of 5 having identical properties to those shown in Example 4.
EXAMPLE 10
(1S, 2S)-2-amino-1-indanol (11)
To triethylamine (1.3 g, 0.013 m) and (1S, 2S)-2-N-methoxycarbonylamino-1-indanol (9), (1.03 g, 0.05 m) in THF (50 ml) was added trichlorosilane (1.20 ml, 0.012 m) via syringe. The mixture was refluxed 4 hr. and then cooled. The mixture was partially concentrated on a rotary evaporator prior to the addition of 25 ml 2N HCl, and then heating on a steam bath was conducted for 15-30 min. After cooling, the mixture was extracted with ether. The aqueous phase was basified with aqueous NaOH and then extracted with ethyl acetate. After drying and concentration, the desired product (11) was obtained. The HCl salt of 11 was formed in ethanol/ether and recrystallized from the same solvent; m.p. 207°-209°; [α] D 25 15.56°(C=0.54, H 2 O) [lit. for the (R,R)-isomer; m.p. 206°-209°; [α] D 25 -13.4°(C=0.75, H 2 O).
Claims to the invention follow. | Amino ketone enantiomers and their direct preparation are disclosed. The ketone may be reduced to yield carbinol enantiomer which has pharmaceutical activity. | 2 |
FIELD OF THE INVENTION
The present invention is in the field of trampoline accessories.
DISCUSSION OF RELATED ART
With development in industry and commerce and improved lifestyle, people are paying more attention to exercise. People need varying levels of physical activities and a variety of different types of sports to match these different needs. The progress has led to developing varying sorts of both exercise types and fitness equipments. The backyard trampoline has become more popular recently for body conditioning. It is said that the trampoline can train one's jumping ability and also improve one's power, balance, and reaction.
A typical trampoline frame is round or rectangular. The trampoline support mostly relies on the bottom of the frame to support the frame above the ground. There is a first bed side which is formed as a net or mesh having an outside face that provides upward restoring force on the surface of the net. When force is applied downward, the surface of the net restores to a neutral position to rebound the mesh bed. Springs connecting the bed to the trampoline frame provide restoring force. Thus, users can bounce on the face of the net for a jumping movement exercise.
Besides providing a rebound surface, the traditional trampoline provides no other feature. Unfortunately, sometimes users become bored with the traditional trampoline leading to dangerous and unsafe activity. Sometimes users discontinue use of the trampoline. It is desired to have an improvement upon the traditional trampoline.
Over time, inventors have improved the traditional trampoline. In United States Patent Publication 2005/0227812, of Oct. 13, 2005 in inventor James describes a trampoline mat and method of making the trampoline. This is an improved trampoline mat is capable of being attached to a trampoline frame using a plurality of coil springs. A variety of structural improvements have been added to the traditional trampoline over time.
Inventor Samuel Chen improved the trampoline United States Patent Publication 2006/0135321 of Jun. 22, 2006 by providing a lighted trampoline, the disclosure of which is incorporated herein by reference.
SUMMARY OF THE INVENTION
A trampoline has a bed. The bed is made of a sheet of fabric having an exterior periphery. A frame includes legs supporting the frame from the ground. A plurality of springs attach the bed to the frame. A light sound module is suspended under the bed. The light sound module includes a light emitting element mounted on a rotation rod. The rotation rod is mounted on a rotation axis, and the rotation rod is driven to rotate by a motor. A plurality of elastic cords has a length, namely a first elastic cord, a second elastic cord, and a third elastic cord.
The first elastic cord has a first elastic cord inside end connected to the light sound module. The second elastic cord has a second elastic cord inside end connected to the light sound module. The third elastic cord has a third elastic cord inside end connected to the light sound module. The first elastic cord has a first elastic cord outside end connected to either the bed or frame. The first elastic cord has a first elastic cord outside end connected to either the bed or the exterior periphery. The second elastic cord has a second elastic cord outside end connected to either the bed or the exterior periphery. The third elastic cord has a third elastic cord outside end connected to either the bed or the exterior periphery.
A plurality of buckle hooks includes a first buckle hook attached to the first elastic cord outside end, a second buckle hook attached to the second elastic cord outside end, and a third buckle hook attached to the third elastic cord outside end. The trampoline may also have a fourth elastic cord having a fourth elastic cord inside end attached to the light sound module, and having a fourth elastic cord outside end connected to either the bed or the exterior periphery.
A first adjustment buckle is attached to the first elastic cord inside end, and the first adjustment buckle adjusts the length of the first elastic cord. A second adjustment buckle is attached to the second elastic cord inside end. The second adjustment buckle adjusts the length of the second elastic cord. The third adjustment buckle is attached to the third elastic cord inside end, and the third adjustment buckle adjusts the length of the third elastic cord.
The light emitting element of the light sound module includes a first LED element at a first radius and a second LED element at a second radius. As the first LED element spins and as the second LED element spins, the first LED element can draw a circle having a first radius and the second LED element can draw a circle having a second radius. The first radius is closer than the second radius to the rotation axis. The first radius can be called the inside radius and the second radius can be called the outside radius. Additional light emitting elements can be linearly disposed on the rotation arm. The rotation arm can be a flexible or rigid printed circuit.
The present invention of a flash spinner is a more sophisticated improvement on the prior art. This invention incorporates a lighted trampoline having a frame, a bounce member and a bounce sensor, sensing bounces to activate lights and provide sounds for entertaining and training purposes. The present invention uses the bouncing movement of the user to activate a sound and light module on a trampoline to provide safety and entertainment to trampoline users.
The present invention provides a trampoline with entertaining sound and light effects including: a frame, a net, an elastic component, a light device, and frame legs. The bottom of the frame has the legs that primarily supports the frame. The bed is mounted to the frame by a set number of springs, also known as elastic components such as helical springs. The bed is is bounded within the frame to form a margin and a bed surface edge. The light device is fixed underneath the bed to be contacted by a user when a user jumps on the bed.
The electrical circuit board at the bottom of the box set is connected to a transparent superstructure. An electric circuit board is connected to vibration sensors. A light and sound emitting unit is powered by a power supply unit that can be a battery box or household electric current. The box set has a peripheral edge with rope holes for receiving a number of elastic rope connections at one end. The elastic rope other end connects to frame. A fixed sound light device vibration trigger can be a spring and pole vibration switch mounted to achieve conduction actuation. The vibration switch is typically soldered to the circuit board to control the light emitting unit. The light-emitting unit of the central box set bottom has a combination of a rotating rod with light emitting elements such as LED's mounted in an array on the rotating rod. The rotating rod is set on the motor shaft. The LED's can be mounted at an angle other than a normal angle. The angular difference can provide a greater field of display. For example, the LEDs can be mounted at a 45° angle to the plane of the rotating rod.
The sound and light device circuit board connection is used to issue music, voice and sound on mounted speakers. To provide additional adjustability, one end of the elastic rope can be connected to an adjustment buckle with the other end of the connection being a button hook.
A sound element is mounted to an electronic circuit housed within the light sound module, and the electronic circuit is actuated by a vibration sensor preferably soldered on the electronic circuit board. The rotation rod can be a printed circuit formed as a strip.
An object of the invention is to allow the user to activate a sound and light device under the mesh bed while the user bounces on the trampoline. The device includes an automatic sensor in the form of the vibration switch that enhances trampoline fun and safety with flashing sound and spinning lights.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an exploded view of the trampoline.
FIG. 2 is an exploded view of the creation of sound and light device stereo.
FIG. 3 is a perspective view of the sound and light module.
FIG. 4 is a bottom view of the sound and light module.
FIG. 5 is a diagram of the attachment of the sound and light module to the trampoline.
FIG. 6 is a cutaway view of the attachment of the light and sound module to the trampoline.
FIG. 7 is a top sectional view of the attachment of the light and sound module to the trampoline.
FIG. 8 is a trampoline side view.
FIG. 9 is a trampoline bouncing action diagram.
FIG. 10 is a trampoline spinning light diagram.
The following call out list of elements can be used as a guide in referencing the elements of the drawings.
1 Frame 11 Supporting leg 2 Bed 3 Spring 4 Sound Light Device 41 Capacity Set Box 411 bottom of the box 42 Circuit Boards 43 Vibration Sensors 44 Light-Emitting Unit 45 Power Supply Unit 47 Elastic Rope 48 Adjustment Buckle 49 Buckle Hook 412 Transparent Superstructure 413 Rope Holes 441 Motor 442 Rotation Rod 443 Light-emitting Element
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
The present invention provides the structure of the trampoline with sound and light effects for entertainment. The invention includes: a frame 1 , a net 2 , an elastic component 3 , and sound light device 4 , where the bottom of the frame features a majority of the supporting leg 11 . The mesh in the frame contains a set number of elastic components connected at set intervals between the frame 1 , margin, and net surface edge. The light device is set at the bottom of the bed 2 that be formed as a net or made of a mesh. The frame 1 has a bed supporting portion and supporting legs. The bed supporting portion has connections for receiving springs 3 . Springs are elastic elements that can be made of metal or fiberglass or even plastic elements. The elastic elements can also be called elastic components.
The sound light device is preferably made as a plastic box that can be round. The plastic box may have an upper transparent superstructure 412 which acts as a lens that fits over a capacity set box 41 that acts as a main housing for the sound light device. The electrical circuit board 42 at the bottom of the capacity set box 41 is connected to a transparent superstructure that can be snapped into place over the capacity set box 41 . The upper transparent superstructure 412 is preferably made of an impact resistant plastic that is soft enough not to crack when jumped upon.
Electric circuit boards 42 are connected to the vibration sensors 43 such that the vibration sensors are part of the electric circuit of the electric circuit boards. The electric circuit boards are preferably printed circuit boards with component soldered on the printed circuit boards.
A light-emitting unit 44 includes a power supply unit 45 to power the lights and speakers of the light emitting unit 44 . The electric circuit board 42 is connected to the driver of the speaker. The driver of the speaker can be a rectangular element mounted facing downward on an underside of the electric circuit board 42 . The electric circuit board 42 can be mounted on a pair of mounting posts with openings disposed on the printed circuit board for allowing a pair of screws to secure the openings to the mounting posts. The driver of the speaker is preferably soldered to the printed circuit board and facing downward. The driver of the speaker emanates sound initially downward which vibrates the capacity set box. The sound then transmits to the transparent superstructure such that the transparent superstructure and the capacity set box become a speaker for transmitting sound vibrations through the air to the user. The bottom surface of the capacity set box 41 can be open with a plurality of openings to allow sound to travel to the user.
The light-emitting unit 44 may include a set of assembled components including the motor 441 , formed as a bottom box mounted to a top surface of the capacity set box on a pair of mounting posts. Preferably, the shaft of the motor directly connects without gearing to a rotation rod 442 . The rotation rod 442 can be flexible and also can be a printed circuit. The rotation rod 442 can also be a printed circuit board in a rigid form.
The rotation rod 442 is formed as a rotating lever and preferably has a counterbalance which can also be lighted. A plurality of light-emitting elements 443 such as a light-emitting diode (LED) can be mounted to a top or bottom surface of the rotation rod 442 . When the light emitting unit 44 is activated, it plays sound to the speaker which can be a discrete element mounted to a bottom side of the circuit board 42 or the speaker can be the entire housing of the sound light device 4 . When the light emitting unit 44 is activated, the motor 441 spins and rotates the rotation rod 442 . The rotation rod 442 as a plurality of light emitting elements that can display a message, display a sequence, or display a light design.
The power supply unit 45 is a battery box. The battery box preferably has a screw for preventing young children from accessing and swallowing the batteries. The power switch 46 pierces the bottom of the box 411 and is accessible from the bottom of the box. The capacity set box 41 peripheral edge has rope holes 413 for a number of elastic rope 47 to connect at an inside end. The adjustment buckle 48 can be used for adjusting a length of elastic cord. The adjustment buckle 48 can be installed toward the inside end of the elastic cord.
The elastic rope 47 connects at an outside end to the frame. When the light sound device receives vibration, it activates. A buckle hook 49 facilitates triggering conduction of vibrations. The circuit board may have a processor to control the light emitting unit. The frame receives a buckle hook mounted on the elastic cord 47 . Alternatively, the buckle hook can be attached to the springs or the external periphery of the bed.
When assembled according to FIG. 10 , the user will stand atop the bed 2 to jump. The mechanical operation is similar to traditional trampoline operation. When the user exerts force on the the bed, the bed 2 will subside in the direction of the force. This will produce a change in the springs 3 , so that original condition of the bed 2 will be restored by the springs 3 . The recovery of the bed rebounds the user upward.
Each time force is exerted on the bed 2 , the bed 2 will subside below the location of the sound light device 4 of the capacity set box 41 . As a result, the elastic rope 47 will pull and stretch, which will cause the elastic rope 47 to pull the capacity set box 41 back to its original condition. The impact of the bed on the sound light device sound light device 4 causes vibrations that trigger vibration sensors 43 to activate by closing circuit on the electric circuit board 42 . The electric circuit board controls the light-emitting unit 44 for moving the light-emitting unit and for activating other sound devices.
The light-emitting unit 44 of the motor 441 drives the rotation rod 442 . While the rotation rod 442 spins, the light-emitting element 443 flickers. This illumination can be intermittent or continuous, and dazzling lighting effects can form around the ring of the trampoline. In addition, the sound light device power switch 46 turns off the device. This allows for the lighting and sound effect to be terminated at the user's discretion.
The present invention preferably provides a trampoline having both sound and light entertainment simultaneously in addition to the bouncing movement. Moreover, in combination with the under bed 2 sound light device 4 , the light-emitting unit 44 preferably provides a spinning motion to the lights, and also affecting the sound to further enhance the fun factor of the trampoline.
The above is the preferred embodiment. It should be pointed out that a person of ordinary skill in the art can further make improvements and polish these improvements without departing from the original scope of the claims. Alterations to the specification can be made within the scope of the claims. For example, the brightness of the lights may be adjusted according to the trampoline bed fabric mesh so that the lights are visible to the user through the trampoline bed. | A trampoline has a bed. The bed is made of a sheet of fabric having an exterior periphery. A frame includes legs supporting the frame from the ground. A plurality of springs attach the bed to the frame. A light sound module is suspended under the bed. The light sound module includes a light emitting element mounted on a rotation rod. The rotation rod is mounted on a rotation axis, and the rotation rod is driven to rotate by a motor. A plurality of elastic cords has a length, namely a first elastic cord, a second elastic cord, and a third elastic cord. | 0 |
RELATED APPLICATION
[0001] This patent application claims the benefit of co-pending U.S. Provisional Patent Application No. 61/432,213, filed on Jan. 13, 2011, which is hereby incorporated by reference in its entirety.
TECHNICAL FIELD
[0002] The present disclosure applies to the field of human medicine. It relates to electrode arrangements or probes that are used as an implant in the human body.
BACKGROUND
[0003] Such implants have been used in diverse embodiments in modern medical technology and are used, e.g., in cardiac pacemakers, ICDs, CRT-Ds and neurostimulators.
[0004] In regard to permanently implantable electrode leads or probes, it is known that parts of the implant can fuse at least partially with endogenous tissue due to the longer residence times in the human body. To reduce this unwanted effect, electrodes or probes are currently provided with surface coatings that are inhibitive in this regard. For example, it is known that a steroid elution counteracts adhesion of electrodes or probes to endogenous tissue. In addition, to improve explantation properties, an objective is to create a surface of the implant that is as entirely smooth as possible, e.g., by embedding the shock coil of an ICD electrode in the electrode body. As an additional measure, an implant design that is isodiametric or tapers in the distal direction is frequently selected.
[0005] Despite these measures, adhesion of electrode leads or probes in endogenous tissue cannot be fully prevented over the long term. This can lead to difficulties when performing explantations, since it cannot be ruled out that parts of the tissue will be destroyed in the process. Such tissue damage can lead to serious complications depending on the region of the body that is involved.
[0006] A particularly critical situation is depicted in FIG. 1 . In this case, as an example, an endocardial ICD electrode 110 is implanted in human heart 100 . It comprises a distal shock coil 120 situated in the right ventricle of the heart 100 and a proximal shock coil 130 disposed largely in the superior vena cava 140 at the outlet of the right atrium. Due to the helical design and despite shape and surface optimization, adhesion 150 of the shock coil with the vascular walls takes place with the majority of these electrodes. In the case of a probe extraction, such adhesions with the vascular wall of the vena cava pose the greatest risk since a vascular rupture of the vena cava can occur here very rapidly. See e.g., Hauser et al., “Deaths and Serious Injuries Associated with ICD and Pacemaker Lead Extraction”, 30 (Abstract Supplement) 277, European Heart Journal (2009).
[0007] On the other hand, leaving deactivated electrodes or probes in the body is not unproblematic, as considered from other perspectives. If such implants are left in the body, complications such as vascular occlusions, interactions of a deactivated electrode with active electrodes, or a contraindication to MRT can result.
[0008] The problem addressed by the present inventive disclosure is therefore that of developing permanently implantable electrode leads or probes that are performed to ensure that the explantation thereof can be performed in a substantially easier manner, or that the occurrence of resultant complications is notably reduced if left in the body.
[0009] The present inventive disclosure is directed toward overcoming one or more of the above-identified problems.
SUMMARY
[0010] This problem is solved in the case of a permanently implantable electrode or probe having the features of the independent claim(s). Further features of advantageous embodiments of the present disclosure are the subject matter of the dependent claims.
[0011] According to the subject matter of the disclosure, an implantable electrode lead or probe comprises at least one control element, the physical-chemical state of which can be manipulated using external excitation such that local degradation or dissolution of a part of the implant or the entire implant—even as a result of the local degradation—takes place in this region. As a result of this process, for example, existing adhesions of an electrode implant with bodily tissue are separated by surface regions of the implanted electrode dissolving at least partially in the region of the adhesions. As an alternative, a stimulated local dissolution of a region of an implanted electrode or probe can be used to taper electrode structures at preferred points, thereby making explantation substantially easier. In the same manner, predetermined breaking points can be specifically created, thereby making it possible to remove substantial parts of an implant without causing significant damage to the tissue.
[0012] The placement and number of regions that can be stimulated to degrade or dissolve by way of the external excitation of control elements can be varied within wide limits depending on the type and application of the implant. For example, either only predefined points or parts of the existing electrode structure or probe can be excited to dissolve while other regions remain unchanged, or, for example, the dissolution process induced by stimulation can affect an entire implanted electrode or probe, thereby reducing the volume thereof overall or even completely dissolving the electrode or probe.
[0013] Various other objects, aspects and advantages of the present inventive disclosure can be obtained from a study of the specification, the drawings, and the appended claims.
DESCRIPTION OF THE DRAWINGS
[0014] The inventive subject matter will be described in greater detail in the following using preferred embodiments, with reference to the drawings and the reference characters noted therein. In the drawings:
[0015] FIG. 1 is a schematic depiction of an endocardial ICD electrode implanted in the human heart, with local tissue adhesion.
[0016] FIG. 2 is a schematic depiction of an electrode implant with local tissue adhesion and explantation of the electrode after stimulated partial dissolution of an outer layer.
[0017] FIG. 3 is a first embodiment of an outer layer of an implantable electrode or probe, which can be degraded using external excitation.
[0018] FIG. 4 is a second embodiment of an outer layer of an implantable electrode or probe, which can be degraded using external excitation.
[0019] FIG. 5 is a third embodiment of an outer layer of an implantable electrode or probe, which can be degraded using external excitation.
[0020] FIG. 6 is an alternative embodiment of an electrode implant that can be partially dissolved using external stimulation.
[0021] FIG. 7 is a schematic depiction of the externally excited dissolution of a part of the electrode implant according to FIG. 6 .
[0022] FIG. 8 is a schematic depiction of the extraction of the inner electrode structure after dissolution of a part of the electrode implant according to FIG. 6 .
[0023] FIG. 9 is separated subcomponents of the electrode implant according to FIG. 6
DETAILED DESCRIPTION
[0024] FIG. 2 shows the distal part of an electrode arrangement comprising outer insulation 210 . This outer region is typically comprised of a material having the greatest possible biocompatibility. “Biocompatibility” refers to the capability of a material to evoke an appropriate tissue response in a specific medical application. This includes an adaptation of the chemical, physical, biological, and morphological surface properties of an implant to the recipient tissue, with the objective of establishing a clinically desired interaction. The biocompatibility of the implant material is furthermore dependent on the timing of the response of the biosystem in which the implant is placed. For example, irritations and inflammations, which can cause tissue changes, occur over the relatively short term. Biological systems therefore respond differently depending on the properties of the implant material. Depending on the response of the biosystem, implant materials can be subdivided into bioactive, bioinert, and degradable/resorbable materials.
[0025] The electrode arrangement depicted in FIG. 2 comprises two stimulation poles (ring 220 and tip 230 ). Endogenous tissue 240 has grown around the electrode lead to a large extent, thereby preventing it from being explanted simply by pulling it out. According to the inventive disclosure, in this embodiment, outer insulation layer 210 comprises regions 250 in which a degradation process of the insulation layer can be triggered by external excitation of control elements. Due to the partial or complete dissolution of these regions 250 of the insulation layer 210 , the adhesion between the surface of the insulation layer 210 of the implanted electrode and the surrounding endogenous tissue 240 is considerably reduced, and the risk of tissue being damaged upon explantation by the implant being pulled out is markedly reduced.
[0026] FIG. 3 shows a schematic depiction of a first embodiment of an implantable electrode or probe which, according to FIG. 2 , comprises an outer coating which, according to the inventive disclosure comprises regions that can be degraded by external excitation. An insulation layer 320 is applied, at least in sections, on inner electrode structure 300 e.g. using a primer 310 . Insulation layer 320 is generally not biocorrodible and can contain, e.g., poly-L-lactide or be composed thereof, or another representative of the polyesters, such as, but not limited to, PDLLA, PLGA, P3HB, P4HB or mixtures or copolymers thereof. As an alternative or in addition thereto, the protective layer can contain Parylene (Parylene C or other derivatives), preferably as Parylene with “pin holes”. In addition thereto or instead thereof, the protective layer can comprise cellulose, preferably as a film, such as, e.g., nitrocellulose, methylcellulose and/or carboxymethyl cellulose. The protective layer can also comprise polyvinyl alcohols, wherein a film formation can be optimized by selecting the molar mass and the degree of deacetylation accordingly. Polyvinyl alcohol is a crystalline polymer that is lightly branched due to the manufacturing process thereof. Polyvinyl acetate is manufactured from vinyl acetate. Polyvinyl acetate is hydrolyzed to form polyvinyl alcohol by reaction with bases. The melting and glass transition temperature depends not only on the degree of hydrolysis and the molar mass, but also on the distribution of acetyl groups (statically or in blocks), the tacticity, and the water content of the polymer. Polyvinyl alcohols having high to moderate degrees of hydrolysis and degrees of polymerization up to 2000 are suitable. The films made from polyvinyl alcohol are tear-resistant and viscoplastic. They are resistant to oil and heat. Polyalcohols such as glycerol and ethylene glycol can be used as softening agents.
[0027] Insulation layer 320 comprises control elements in the form of perforation points 330 which are filled with a hydrogel. A hydrogel is a polymer that contains water but is insoluble in water, the molecules of which are coupled either chemically, e.g., by covalent or ionic bonds, or physically, e.g., by forming loops of the polymer chains to form a three-dimensional network. Hydrogels according to the inventive disclosure are capable of undergoing changes in volume in response to external excitation in that they have a variable swelling capacity and can therefore absorb quantities of water per mmol of hydrogel polymer that differ in a controllable manner.
[0028] These hydrogels can be made, e.g., by reacting ethylenically unsaturated monomers and polymers which carry ionizable groups with cross-linking agents and polymerization catalysts. As an alternative thereto, suitable hydrogels can be made using condensation reactions with difunctional and multifunctional monomers. Suitable monomers and polymers and methods for their manufacture are known to a person skilled in the art and need not be described in detail herein. Likewise, methods for the manufacture of suitable hydrogels using such monomers or polymers or combinations thereof are also known to a person skilled in the art and will not be described in detail herein. Preferable hydrogels contain, for example, a polymer based on acrylamide, methacrylamide, dimethylaminoethyl methacrylate, or a derivative of acrylamide, methacrylamide, or dimethylaminoethyl methacrylate. Other preferred hydrogels contain, for example, a polymer based on poly(N-isopropylacrylamide) or poly-N-isopropylacrylamide-co-allylamine or poly(N-isopropylamide) (PNIPAM) or mixtures thereof with poly(p-dioxanon) as the hard segment.
[0029] The expression “swelling capacity” according to the inventive disclosure refers to the property of the hydrogel to absorb a certain quantity of water per mmol of hydrogel polymer. Reduced swelling capacity results in a reduction of the volume of the hydrogel and, therefore, to a change in shape of the hydrogel. Suitable methods and measurement procedures for determining the swelling capacity are known to a person skilled in the art; measurement procedures that have already been proven repeatedly in the field of galenics are particularly suitable.
[0030] Preferably, hydrogels are used that have a temperature-depending swelling capacity. Particularly preferred hydrogels have a swelling capacity that diminishes as the temperature rises. Such hydrogels can be, for example, those wherein their swelling capacity diminishes by at least 30%, preferably by up to 50%, and particularly preferably by 30% to 50%, given a temperature increase of approximately 10K.
[0031] The temperature dependence of the hydrogel is preferably selected such that it has a pronounced hysteresis effect in regard to the swelling properties and, therefore, the swelling capacity remains reduced even after return to a starting temperature of approximately 37° C.
[0032] As depicted schematically in FIG. 3 , in this embodiment, a temporary heating of insulation layer 320 and, therefore, the hydrogel, can be initiated in perforation points 330 via external impression of high-frequency energy using, for example, a high-frequency transmitter 340 . Preferably, the wavelength of high-frequency transmitter 340 is matched to the antenna geometry 350 of the electrode structure, thereby ensuring that heating is effective. The induced heating of the electrode structure also warms the hydrogel and reduces the swelling properties thereof to the extent that the hydrogel undergoes a deformation resulting in a reduced hydrogel volume 360 , thereby largely exposing perforation point 330 in insulation layer 320 . Given an appropriate number of such perforation points 330 , the reduction of the hydrogel volume results in a considerable overall reduction in the adhesion between the surface of insulation layer 320 and the surrounding endogenous tissue.
[0033] FIG. 4 shows an alternative embodiment of an outer layer of an implantable electrode or probe, which can be degraded using external excitation. In this case as well, an insulation layer 420 having perforation points 440 is applied to electrode structure 400 of an implant using primer 410 . Insulation layer 420 contains magnetic nanoparticles 430 . Perforation regions 440 are also closed in this embodiment using a hydrogel. In this embodiment, a hydrogel having a discontinuous swelling capacity is used, which abruptly collapses to a reduced hydrogel 460 above a certain temperature (e.g., above 45°-50° C.), and thereby “drops out” of the perforation point 440 of the protective layer. Insulation layer 420 and, therefore, the hydrogel, are heated in this case using, for example, an alternating magnetic field which is impressed by an external magnetic alternating field generator 450 . Magnetic nanoparticles 430 are induced to oscillate by the alternating magnetic field, thereby heating insulation layer 420 and the hydrogel in perforation points 440 .
[0034] In the embodiments depicted in FIGS. 3 and 4 , once external excitation has taken place and perforation points 330 , 440 have therefore been opened, bodily medium can also reach inner electrode structure 300 , 400 provided adhesion bridge 310 , 410 has been performed to be permeable thereto. If a biocorrodible metallic material is selected in addition for inner electrode structure 300 , 400 , then, due to contact with bodily medium, the degradation process triggered by external excitation also affects inner electrode structure 300 , 400 in the regions in which insulation layer 320 , 420 has perforation sites 330 , 440 . A “bodily medium” according to the inventive disclosure is understood to be all media that are naturally present in the human body or that are additionally incorporated via absorption into the body. This includes, but is not limited to, fluids that contain water, such as blood, lymph, saliva and other substances, in particular ions, and also includes gasses, such as, for example, carbon dioxide, hydrogen, oxygen, and nitrogen.
[0035] In the field of biocorrodible metallic materials, magnesium or pure iron are typically used, as are biocorrodible base alloys of the elements magnesium, iron, zinc, molybdenum, tungsten, or aluminum. In addition, alloys of the aforementioned base elements additionally comprising one element from the group of alkaline metals or alkaline-earth metals are known. Alloys based on magnesium, iron and zinc are described as being particularly suitable. Minor constituents of the alloys can be, for example, manganese, cobalt, nickel, chromium, copper, cadmium, lead, tin, thorium, zirconium, silver, gold, palladium, platinum, silicon, calcium, lithium, aluminium, zinc and iron. Particularly suitable is the use of a biocorrodible magnesium alloy having a portion of magnesium >90%, yttrium in the range 3.7-5.5%, rare earth metals in the range 1.5-4.4%, and the rest <1% of other materials.
[0036] By combining a coating which is locally degradable by external excitation of control elements and an electrode structure comprised of biocorrodible material, predefined parts of an implanted electrode structure—or the entire electrode structure—can be specifically incorporated in a corrosion process by arranging the degradation points accordingly.
[0037] FIG. 5 shows a schematic depiction of another embodiment of the inventive disclosure, in the case of which, after external excitation of control elements, degradation of local regions of an insulation layer begins and, due to the formation of pores, contact of bodily fluid with inner electrode structures of the implant is induced. In this embodiment as well, an insulation layer 520 is applied to inner electrode structure 500 of the implant using primer 510 . In this embodiment, primer 510 also contains molded bodies 530 as control elements which are comprised of a biocompatible, and preferably biodegradable, memory-effect polymer. Memory-effect polymers are plastics that have a so-called “shape memory” effect. A “shape memory” effect is understood to mean that a memory-effect polymer can be stably transferred from an original shape into another shape in which it remains until the memory-effect polymer returns to a previous shape or the original shape, e.g., in response to external excitation.
[0038] In the embodiment shown, the original shape of the memory-effect polymer is curved, and the planar shape of molded body 530 is the “deformed state” (set at approximately 125° C.) of the memory-effect polymer. Electrode structure 500 and, therefore, adjacent molded bodies 530 are heated to approximately 45° C. for at least 10 seconds using, for example, a high-frequency energy impressed using an external high-frequency transmitter 540 . Preferably, the wavelength of the high-frequency transmitter 540 is matched to the antenna geometry 550 of the electrode structure, thereby ensuring that heating is effective. The memory-effect polymer of molded body 530 thereby assumes its original, curved shape, as shown at 560 . Insulation layer 520 is partially perforated by molded bodies 560 , the shape of which has now been changed, and bodily fluid reaches inner electrode structure 500 in this region.
[0039] As an alternative, the deformation of the memory-effect polymer can also be triggered by light in this case. According to one conceivable application, the deformation is triggered by irradiation of UV light having a wavelength of less than 260 nanometers, e.g., using fiber optic catheters.
[0040] FIGS. 6-9 show an alternative embodiment of an electrode structure that can be partially dissolved using external stimulation. The implant is comprised of an outer insulation tube 610 , a bipolar electrode connector 620 , metallic electrode leads 630 , and at least one electrode pole 640 . In the configuration shown, the leads and the electrode head having metallic fixators 660 , 670 are securely connected in the distal region to the external insulator, and therefore the electrode structure forms a stable unit.
[0041] In the case of this embodiment, as shown in FIGS. 6-9 and according to the inventive disclosure, before explantation of this electrode structure, the region of fixators 660 , 670 , as control element, can be specifically excited externally. This is depicted in FIG. 8 . By application of an appropriate voltage 680 , via electrode connector 620 , the potential difference initiates corrosion of the fixators ( 660 ′, 670 ′). Depending on the duration of exposure to external excitation, fixators 660 , 670 are thereby weakened or, as shown in FIG. 8 , are even fully dissolved and the inner electrode structure can be pulled out relative to outer insulation 610 .
[0042] As shown in FIG. 9 , the initially one-piece electrode implant breaks down into two separable components due to the degradation of the local region 660 , 670 induced by external excitation. All conductive components, i.e., electrode connector 620 , metallic electrode leads 630 , and electrode pole 640 , can therefore be extracted. Outer insulation layer 610 can then also remain in the body and be used as an introduction channel, e.g., for a new electrode.
[0043] A region which can be introduced to local corrosion according to the inventive disclosure using external excitation of control elements, as illustrated in FIGS. 7 to 9 , can be provided at various predefined points of an implantable electrode structure or probe. It is therefore possible to specifically electrolytically dissolve various regions of the electrode structure by applying appropriate external voltage using different potential differences. The rate of the individual dissolution process can be controlled by the selection of the metallic material and the potential difference. The procedure can therefore be adjusted such that compatibility for the human organism is ensured during the dissolution procedure.
[0044] The external excitation of control elements as the trigger for degradation processes at specified regions of implantable electrode structures or probes can also take place, in an alternative manner, by the administration of drugs or the application of special chemical substances that induce dissolution of local regions of the electrode structure, e.g., by catalytic action. For this purpose, an implanted electrode structure comprises appropriate regions of selected materials at the desired points, which enter into physical/chemical interaction with the added substances in the sense of degradation.
[0045] All of the embodiments of the inventive disclosure shown can also be combined, and therefore, e.g., regions can be provided on an electrode structure that degrade by external HF excitation, but regions can also be present that corrode electrolytically using an externally applied potential difference.
[0046] Although certain embodiments have been illustrated and described herein, it will be appreciated by those of ordinary skill in the art that a wide variety of alternative or equivalent embodiments or implementations, calculated to achieve the same or similar purposes, may be substituted for the embodiments illustrated and described herein without departing from the scope of the present invention. Those of skill in the art will readily appreciate that embodiments in accordance with the present invention may be implemented in a very wide variety of ways. This application is intended to cover any and all adaptations and/or variations of the embodiments discussed herein.
[0047] The terms and expressions which have been employed in the foregoing specification are used therein as terms of description and not of limitation, and there is no intention, in the use of such terms and expressions, to exclude equivalents of the features shown and/or described or portions thereof, it being recognized that the scope of the invention is defined and limited only by the claims that follow.
[0048] It will be apparent to those skilled in the art that numerous modifications and variations of the described examples and embodiments are possible in light of the above teachings of the disclosure. The disclosed examples and embodiments are presented for purposes of illustration only. Other alternate embodiments may include some or all of the features disclosed herein. Therefore, it is the intent to cover all such modifications and alternate embodiments as may come within the true scope of this invention, which is to be given the full breadth thereof. Additionally, the disclosure of a range of values is a disclosure of every numerical value within that range. | The present disclosure relates to permanently implantable electrode structures or probes of the type used, in particular, in cardiac pacemakers, ICDs, CRT-Ds and/or neurostimulators. Such electrode structures or probes include at least one control element, the physical-chemical state of which can be specifically manipulated using external excitation, such that local degradation or dissolution of a part of the implant or the entire implant takes place in this region. As a result of this partial dissolution, for example, the electrode structure or at least a portion thereof is modified such that the conditions for explantation are improved and/or parts of an implanted electrode structure that remain in the body are functionally deactivated. | 0 |
TECHNICAL FIELD
[0001] The present invention relates to novel glutamate receptors and utilization thereof; more specifically to a glutamate receptor, DNA which encodes the receptor, a transformed cell expressing the receptor, a method for producing the receptor, a method for identifying an agonist, antagonist, or allosteric modulator for glutamic acid, a method for identifying an agonist for glutamic acid, an antibody to the receptor, and processes for making glutamate receptor modulators and pharmaceutical compositions comprising said modulator.
BACKGROUND ART
[0002] Human sense of taste is believed to be constituted of five basic tastes—salty, sweet, acidic, bitter and umami taste (relishable taste). Each taste is generated by the binding of a taste substances to each receptor specifically expressed in taste cells existing in taste buds of the tongue. Until now, ENaC/Deg. (salty taste receptor), EnaC, ASIC, HCN (acidic taste), T2R family (bitter taste receptor), T1R2/T1R3 (sweet taste receptor), Taste mGluR4 (umami taste receptor), etc. have been cloned as candidates of the taste receptors (As to details, refer to Lindemann, B., Nature, 413; 13, 219-225, 2001; the cited document is incorporated by reference in the present specification; that is the same hereinafter as well).
[0003] A low-affinity glutamate receptor expressed in taste bud cells in the rat found by Chaudhari, N., Landin, A. M., Roper, S. D., et al. as an umami taste receptor has been a convincing evidence for proving the umami taste-receiving mechanism at molecular level ( Nat. Neurosci., February 2000;3(2):113-9). The umami taste receptor has the same host gene as that in type 4 (mGluR4) which is a subtype of glutamate receptor of a rat brain type/a metabotropic type (Tanabe, Y., et al., Neuron, January 1992;8(1):169-79; Flor, P. J., et al., Neuropharmacology, February 1995;34(2):149-55); and since taste type mGluR4 holds a partially deficient extracellular domain by a splicing variation, the finding of specific working substances other than glutamic acid that can utilize the present new type variant as a peripheral glutamate receptor has been receiving public attention.
[0004] Glutamic acid is a major excitatory neurotransmitter in the central nervous system, and it is widely accepted that its abnormal control is involved in progressive encephalopathies such as memory disorders, ischemic encephalopathy, amyotropic lateral sclerosis (ALS), Parkinson's disease, and Huntingon's chorea (Meldrum, B. S., Neurology, November 1994;44 (11 Supple8):S14-23; Nishizawa, Y., Life Sci. Jun. 15, 2001;69(4):369-81). Therefore, many studies concerning glutamate receptors have been carried out up to now in cranial nerve system. Many receptors (three kinds of ionotropic receptors and eight kinds of metabotropic receptors) have been found in the central nervous system with their splicing variants as well. Particularly, since 1992 when metabotropic glutamate receptor type I (mGluR1a) was cloned by Nakanishi, et al., at least three splicing variants (mGluR1b, mGluR1c and mGluR1d) have been confirmed as mGluR1 variants (As to details, refer to Hermans, E. and Challiss, R. A., Biochemical J., 359:465-484, 2001). In all of those variants, the C-terminal region of mGluR1a becomes short, and their existence in nerve cells and glia cells has been confirmed. On the basis of such abundant receptor information, development for working drugs which are specific to each receptor has been extensively carried out. Even today new therapeutic drugs in the treatment of the above-mentioned diseases are being developed (As to details, refer to Barnard, E. A., Trends Pharmacol. Sci., May 1997;18(5):141-8; Schoepp, D. D., Conn. P. J., Trends Pharmacol. Sci., January 1993;14(1):13-10).
[0005] Nowadays, we have several pieces of knowledge that suggest physiological functions of the peripheral glutamate receptor (Berk, M., Plein, H., Ferreira, D., Clin. Neuropharmacol., May-June 2001;24(129-32; Karim, F., J. Neurosci. Jun. 1, 2001;21(11):3771-9; Berk, M., Plein, H., Belsham, B., Life Sci. 2000;66(25):2427-32; Carlton, S. M., Goggeshall, R. E., Brain Res. Feb. 27, 1999;820(1-2):63-70; Haxhij. M. A., Erokwu, B., Dreshaj, I. A., J. Auton. Nerv. Syst. Dec. 11, 1997;67(3):192-9; Inagaki, N., FASEB J. May 1995;9(8):686-91; Erdo, S. L., Trends Pharamcol. Sci., November 1991;12(11):426-9; Aas, P., Tanso, R., Fonnum, F., Eur. J. Pharamacol. May 2, 1989;164(1):93-102; Said, S. I., Dey, R. D., Dickman, K., Trends Pharmacol. Sci. July 2001;22(7):344-5; Skerry, T. M., Genever, P. G., Trends Pharamacol., Sci. April 2001;22(4):174-81). However, those peripheral glutamate receptors are expressed in peripheral nerves, smooth muscle and immune tissues. There has been no report for their expression in epithelium of tongue and digestive tract. In mammals including humans to maintain normal growth and health, it is necessary to orally take up required amounts of nutrients at a an specific timing and excrete disposable matter. This is actually done by the digestive tract, which is a single tube consisting of oral cavity, stomach, small intestine and large intestine. The process of digestion and absorption is controlled by intrinsic intestinal neuroplexus and extrinsic cranial nerves.
[0006] The judgment as to whether or not to take a necessary nutrient is the result of brain integration of a signaling pathway that the individual is aware of taste with an autonomous signaling pathway that the individual is unaware of visceral sense. It is considered that salty taste (sodium, potassium, etc.) serves as a marker of minerals and is required for maintaining the osmotic pressure of the body fluid; sweetness (glucose) serves as a marker of carbohydrates and is required for supplementing energy; umami (sodium glutamate) serves as protein marker and is useful for supplementing energy and essential amino acids; and bitterness serves as a marker for toxic substances. That is, necessary nutrients are taken up relying on the tastes thereof. Then, if necessary amounts are ingested, satiation is determined by a series of intracerebral processes coming from the signal input to the solitary tract nucleus. Those signals are derived from activated vagus afferent fibers through nutrient sensors existing in the stomach, small intestine, and hepatoportal vein (Bray, G. A., Proc. Nutr. Soc., 2000;59:373-84; Bray G. A., Med. Clin. North. Am. 1989:73:29).
[0007] On the other hand, physiological studies on the mechanism for chemical sensation in the digestive tract have been performed for a long time. It is supposed that there are sensors that detect the content of the digestive tract (for the details, reference is made to Mei, N., J. Auton. Nerv. Syst., 1983;9:199-206; Mei, N., Lucchini, S., J. Auton, Nerv. Syst., 1992;41:15-8). The digestive chemosensory system includes a glucose sensor (Mei, N., J. Physiol. (Lond.) 1978, 282, 485-5-6), a temperature sensor (El Ouazzani, T., Mei, N., Exp. Brain Res. 1979;15;34:419-34), an osmotic pressure sensor (Mei, N., Garnier, L., J. Auton. Nerv. Syst., 1986;16:159-70), a pH sensor, an amino acid sensor (Mei, N., Physiol. Rev., 1985;65:211-37), and a stretch sensor (Barber, W. D., Burks, T. F., Gastroenterol Clin. North. Am. 1987; 16:521-4).
[0008] In particular, a sensor that recognizes glutamic acid was suggested by Niijima et al. from neural excitation that occurred when glutamic acid was administered in the digestive tract. In this experiment, the technique of recording neural discharge activity was used for the stomach branch and abdominal cavity branch of the vagus nerve. Those vagal branches control mainly the stomach and small intestine and responded to glutamic acid; therefore was assumed that there is a mechanism that recognizes this amino acid at the vagus nerve ending (Niijima, A., Physiol. Behav., 1991;49:1025-8).
DISCLOSURE OF THE INVENTION
[0009] Although many studies have been made on glutamate receptors and digestive tract sensors as described above, to date, glutamate perception is unclear and no progress has been made in recent works. Failure of receptor isolation from tissues containing glutamate sensors (receptor, transporter, etc.) necessary for nutrient recognition in the mucous membrane of the digestive tract prevented the progress in this research field. The inventors of the present invention expect that elucidation of the umami-like substances that bind to glutamate sensors in the digestive tract would enable development of drugs and the like directed to control of the nutrient recognition mechanism described below.
[0010] That is, the nutrient recognition mechanism also plays an important role on satiety or surfeit and improves poor physical condition in edacity and imbalance when indulging nutrients in eating disorders. It is considered that abnormal recognition of nutrients in the digestive tract naturally results in disturbance in the overall process of digestion and absorption, thus causing edacity, eating disorders, inappetence, indigestion, diarrhea, constipation, etc. Medically, there are many factors involved in the development of digestive diseases such as ulcers (stomach ulcer, duodenum ulcer) due to psychogenetic hyperphagia, cibophobia, obesity, anomaly of acid secretion, anomaly of blood flow in digestive tract, anomaly of secretion of digestive enzymes, etc., stress ulcers, drug-caused (NSAIDs, etc.) acute ulcers, ischemic ulcer (ischemic colitis), diabetes due to anomaly of secretion of insulin or anomaly of secretion of digestive tract hormone, heavy stomach, nausea, constipation, diarrhea, hypersensitivity bowel syndrome, etc. due to anomaly of gastrointestinal motility and so forth.
[0011] Further, in recent years, the abrupt increase in obesity incidence is a social phenomenon. Many of those who are obese are said to have decreased basal metabolism and tend to eat too much. How to control the appetite of obese individuals is of great social concern. Many try to be on an excessive diet. However, in most cases, they are unsuccessful. Thus, improving the mechanism of nutrient recognition in the digestive tract and achieving satiety with a normal meal is very important to those who are obese.
[0012] The second object of the present invention is derived from the above-mentioned viewpoint, and the matter to be solved is identification of an actual glutamate-like substance which binds to glutamate sensors in the epithelium of the tongue and the digestive tract and methods for utilizing such sensors are provided.
[0013] The present inventors have investigated a receptor distribution in the epithelium of the tongue and in the digestive tract by way of an immunohistological methods using antibodies that recognize the intracellular domain of the metabotropic glutamate receptor type 1 (mGluR1). As a result, it has been found that cells in the epithelium of the tongue and the mucous membrane layer of the stomach are positive for mGluR1 where the receptor is present. In the tongue epithelium, the apical site of taste cells from taste buds are positive for mGluR1. Whereas in the stomach, mucus-secreting cells (neck mucus cells) and pepsinogen-secreting cells (chief cells) at the body of the stomach and mucous cells at the antrum of the stomach are positive for mGluR1. cDNA cloning from tongue epithelium was successfully performed, which has produced a novel glutamate receptor. It is expected that this glutamate receptor is a novel umami taste receptor or a digestive tract glutamate sensor which was previously unknown and that the receptor cDNA, a purified receptor, and the receptor-expressing cells are useful for screening for modulators of umami taste receptor and digestive tract glutamate sensor.
[0014] The present invention has been achieved on the basis of the above findings and its summary is as follows.
[0015] (1) A glutamate receptor protein comprising:
[0016] (A) a transmembrane domain and an intracellular domain common to the type 1 metabotropic glutamate receptor; and
[0017] (B) an extracellular domain which is shorter than type 1 metabotropic glutamate receptor by 481 or 409 amino acid residues.
[0018] (2) The glutamate receptor protein according to (1), wherein it is expressed on epithelium of tongue of rat.
[0019] (3) The glutamate receptor protein according to (1), wherein it has an amino acid sequence represented by SEQ ID NO: 6 and NO: 8 or an amino acid sequence represented by amino acid nos. 73 to 790 and 73 to 497 in the above amino acid sequence.
[0020] (4) The glutamate receptor protein according to (3), wherein it contains substitution, deletion, insertion or addition of one or plural amino acid residue(s) and is able to generate a second messenger by binding with glutamic acid.
[0021] (5) DNA which codes for the glutamate receptor protein mentioned in any of (1) to (4) and does not express the type 1 metabotropic glutamate receptor protein.
[0022] (6) A cell which holds DNA coding for the glutamate receptor protein mentioned in any of (1) to (4) in an expressible form.
[0023] (7) A method for the manufacture of a glutamate receptor protein, characterized in that, cells which hold DNA coding for the glutamate receptor protein mentioned in any of (1) to (4) in an expressible form are incubated in a medium whereupon the glutamate receptor protein is produced and then the glutamate receptor protein is collected from the above-mentioned cells.
[0024] (8) A method for the search of agonist, antagonist or allosteric modulator for glutamic acid, characterized in that, the glutamate receptor protein mentioned in any of (1) to (4) is made to react with a substance which binds to that protein in the presence of a substance to be tested whereupon inhibition or promotion of the reaction is detected.
[0025] (9) A method for the search of agonist for glutamic acid, characterized in that, the glutamate receptor protein mentioned in any of (1) to (4) is made to react with a substance to be tested whereupon the reaction is detected.
[0026] (10) The method according to (8), wherein the glutamate receptor protein from the cell of (6) or a membrane fraction prepared from the cell is used.
[0027] (11) The method according to (10), wherein inhibition or promotion of the above binding is detected by a second messenger generated by the glutamate receptor protein.
[0028] (12) The method according to (9), wherein the glutamate receptor protein from the cell of (6) or a membrane fraction prepared from the cell is used.
[0029] (13) The method according to (12), wherein inhibition or promotion of the above binding is detected by a second messenger generated by the glutamate receptor protein.
[0030] (14) An antibody which specifically binds to the glutamate receptor protein mentioned in any of (1) to (4).
[0031] (15) A method for the manufacture of a drug for the adjustment of a second messenger which is generated by binding of glutamic acid to a glutamate receptor comprising
[0032] a step where the glutamate receptor protein mentioned in any of (1) to (4) is made to react with a substance which binds to said protein in the presence of a substance to be tested to detect inhibition or promotion of the reaction whereby agonist, antagonist or allosteric modulator for glutamic acid is searched and
[0033] a step where a pharmaceutical composition is prepared using the agonist, antagonist or allosteric modulator for glutamic acid prepared in the above step as an effective ingredient.
[0034] (16) A method for the manufacture of a drug for the adjustment of a second messenger which is generated by binding of glutamic acid to a glutamate receptor comprising
[0035] a step where the glutamate receptor protein mentioned in any of (1) to (4) is made to react with a substance to be tested to detect inhibition or promotion of the reaction whereby agonist for glutamic acid is searched and
[0036] a step where a pharmaceutical composition is prepared using the agonist for glutamic acid prepared in the above step as an effective ingredient.
[0037] The present invention will now be illustrated in detail as hereunder.
[0038] Typically, the glutamate receptor protein of the present invention is any of a protein having an amino acid sequence represented by amino acid nos. 1 to 718 in the SEQ ID NO: 2 in the Sequence Listing, a protein having an amino acid sequence represented by amino acid nos. 1 to 425 in the SEQ ID NO: 4 in the Sequence Listing, a protein having amino acids 1 to 790 in the SEQ ID NO: 6 in the Sequence Listing and a protein having amino acids 1 to 497 in the SEQ ID NO: 8 in the Sequence Listing. An open reading domain of a base sequence of rat cDNA coding for the present protein is shown in SEQ ID NOS: 1, 3, 5, 7, 9 and 10.
[0039] Since a variant of the glutamate receptor protein as such is a metabotropic glutamate type 1 receptor (mGluR1) of a taste type found from epithelial cells of tongue, the present inventors named it as mGluRT; further, in view of homology of the sequences, the protein coded by SEQ ID NOS: 1 and 3 was named mGluRTα, the protein coded by SEQ ID NOS: 5 and 7 was named mGluRTβ and the protein coded by SEQ ID NOS: 9 and 10 was named mGluRTγ. In mGluR1, there have been known two types, i.e. type A (mGluR1a) and type B (mGluR1b), depending upon the splicing variation of C-terminal, and in the proteins of the present invention, proteins coded by SEQ ID NOS: 1 and 3, 5 and 7 and 9 and 10 are also variants corresponding to type A and type B, respectively. So the protein coded by SEQ ID NO: 1 was named mGluRTαa; the protein coded by SEQ ID NO: 3 was named mGluRTαb; the protein coded by SEQ ID NO: 5 was named mGluRTβa; the protein coded by SEQ ID NO: 7 was named mGluRTβb; the protein coded by SEQ ID NO: 9 was named mGluRTγa; and the protein coded by SEQ ID NO: 10 was named mGluRTγb. Hereinafter, the glutamate receptor proteins of the present invention may be generally referred to as mGluR1 variants in the present specification. When an appropriate promoter is linked to upstream region of the base sequences represented by SEQ ID NOS: 1, 3, 5, 7, 9 and 10 and is expressed within an appropriate cells, it is possible to produce active glutamate receptors.
[0040] Comparison of the amino acid sequence of the present invention with that of brain-type metabotropic glutamic type 1 receptor (hereinafter referred to as mGluR1) which has been confirmed to be present in the brain is shown in FIG. 1 . The C-terminal side of mGluRTαa (amino acid numbers 1 to 718 in SEQ ID NO: 2) is identical with each C-terminal side of mGluR1a, and the C-terminal side of mGluRTαb (amino acid numbers 1 to 425 in SEQ ID NO: 4) is identical with C-terminal side of mGluR1b, respectively; but as compared with mGluR1, both N-terminal side were shorter to an extent of 481 amino acid residues. On the other hand, mGluRTβ and mGluRTγ had the same coding regions, and in both of them, C-terminal sides (amino acid numbers 1 to 790 in SEQ ID NO: 6) of type A (mGluRTβa and mGluRTγa) are identical with that of mGluR1a; while, C-terminal sides (amino acid numbers 1 to 497 in SEQ ID NO: 8) of type B (mGluRTβb and mGluRTγb) are identical with that of mGluR1b; but, as compared with mGluR1, N-terminal side was shorter to an extent of 409 amino acid residues. As will be mentioned later, it is believed that the glutamate receptor of the present invention is a splicing variant derived from gene which is common to mGluR1. Hereinafter, the glutamate receptor protein may be wholly called as mGluR1 variants in the present specification.
[0041] When the cDNA sequence coding for mGluR1 variants are compared with mGluR1 mRNA sequence, it was suggested that they were derived from common gene. Thus, mGluR1 variants are presumed to be the result where exon in mGluR1 gene was deleted by an alternative splicing. The detail is shown in FIG. 1 . Brain-type mGluR1 comprises exons 1 to 9; and for subtypes, type A (mGluR1a) comprises exons 1 to 7 and 9, and type B (mGluR1b) comprises exons 1 to 8 (refer to FIG. 1A ). On the other hand, among mGluR1 variants of the present invention, mGluRTαa comprises exons 5 to 7 and 9, mGluRTαb comprises exons 5 to 8 (refer to FIG. 1B ), mGluRTγa comprises exons 3 to 7 and 9, mGluRTβb comprises exons 3 to 8, mGluRTγa comprises exons 4 to 7 and 9, and mGluRTγb comprises exons 4 to 8 (refer to FIG. 1C ). Since initiation methionine codon is not present in exon 3 constituting mGluRTβ, coding region of mGluRTβ starts from methionine in exon 4; as a result, coding regions of mGluRTβ and mGluRTγ are common. Here, exons 1 to 6, exon 7 and exons 8 to 9 correspond to extracellular domain, seven transmembrane domain and intracellular domain, respectively.
[0042] FIG. 2 shows the structures of mGluR1 and mGluR1 variants. mGluR1 comprises intracellular domain (exons 1 to 6), seven transmembrane domain (exon 7) and extracellular domain (type A: exon 9; type B: exon 8). mGluR1 variants also have the same intracellular domain and seven transmembrane domain as mGluR1 has, and it has the same sequence as those of mGluR1.
[0043] Incidentally, mGluRTα starts from exon 5; therefore, the amino acid sequence of SEQ ID NO: 2 (mGluRTαa) corresponds to 73 to 790 of the amino acid sequence in SEQ ID NO: 6 (mGluRTβa and mGluRTγa), and the amino acid sequence of SEQ ID NO: 4 (mGluRTαb) corresponds to 73 to 497 of the amino acid sequence in SEQ ID NO: 8 (mGluRTβb and mGluRTγb).
[0044] Thus, the mGluR1 variants of the present invention have the same transmembrane domain and intracellular domain as those of type 1 metabotropic glutamate receptor protein and has extracellular domain which is shorter to an extent of 409 or 481 amino acid residues than type 1 metabotropic glutamate receptor protein. Thus, the mGluR1 variant of the present invention is different from mGluR1 in terms of extracellular domain which is an acting site to ligand; therefore, it is presumed to be different from mGluR1 in terms of affinity to ligand. Meanwhile, it is common to mGluR1 in intracellular domain which is an effector domain of seven transmembrane G protein conjugate receptor (GPCR); therefore, it is a functional receptor which is able to generate a second messenger.
[0045] The mGluR1 variant of the present invention may be derived from a rat. Alternatively, so long as it can generate a second messenger when glutamic acid is bound thereto, the mGluR1 variant may be derived from any animal including mammalian such as human, monkey, mouse, dog, cow, and rabbit, birds, and fin. In the case where the mGluR1 variant is used as a component of pharmaceutical composition, it is preferably derived from a mammalian.
[0046] The mGluR1 variant of the present invention may be a protein having the amino acid sequence of SEQ ID NO: 6 or the amino acid sequence consisting of amino acid numbers 73 to 790 in SEQ ID NO: 6 (SEQ ID NO: 2), a protein having the amino acid sequence of SEQ ID NO: 8 or the amino acid sequence consisting of amino acid numbers 73 to 7497 in SEQ ID NO: 8 (SEQ ID NO: 4), or a protein having the amino acid sequence any of SEQ ID NOS: 2, 4, 6 and 7 including substitution, deletion, insertion or addition of one or a plurality of amino acids at one or a plurality of sites so long as it has properties of generating a second messenger when glutamic acid is bound thereto.
[0047] The “plurality” as used herein varies depending on the positions of amino acid residues in the three-dimensional structure of the protein and the types of the amino acids, however, the number may be such that the homology with the amino acid sequence shown by any of SEQ ID NOS: 2, 4, 6 and 8 is 80% or more, preferably 90% or more. More particularly, the plurality is 2 to 115, preferably 2 to 58, more preferably 2 to 30.
[0048] The glutamate receptor of the present invention may be in a purified or isolated form; however, when the activity is required, it is preferably in a form that is expressed in a suitable cells and localized in the membrane of the cell or in a form contained in a membrane fraction prepared from a cell in which the mGluR1 variant was expressed. Thus, the glutamate receptor of the present invention also includes cells that express mGluR1 variant or a membrane fraction prepared from such cells.
[0049] The mGluR1 variant can be obtained, for example, by introducing DNA that encodes the mGluR1 variant into a suitable host cell to express the mGluR1 variant. The above-mentioned DNA includes gene that encodes the mGluR1 variant, isolated from the chromosome of a cell of a mammalian such as mouse. When chromosomal gene is used, it is preferable that cDNA is used since it is considered necessary to control a post-transcriptional process such as splicing so that mGluR1 variant can be generated.
[0050] The cDNA of mGluR1 variant can be cloned by amplifying the cDNA of mGluR1 variant using RNA prepared from the epithelium of tongue of a mammal such as a rat as a template, and oligonucleotides shown in the embodiments as primers. In addition, since the structure of mGluR1 variant, particularly unique structure on the N-terminal region has been made clear by the present invention, cloning and identification of the cDNA of mGluR1 variant can be performed easily based on the structures. The open reading frame nucleotide sequence of the thus obtained cDNA of mGluR1 variant is shown in each SEQ ID NOS: 1, 3, 5, 7, 9 and 10.
[0051] Thus, another feature of the present invention is a polynucleotide coding for any of mGluR1 variants of the present invention. With regard to the polynucleotide coding for any of mGluR1 variants of the present invention, anything which contains a base sequence (DNA or RNA, preferably DNA) coding for the above-mentioned mGluR1 variant of the present invention may be used provided that it does not code for brain-type mGluR1. Such a polynucleotide is DNA and RNA such as mRNA coding for the mGluR1 variant of the present invention and may be double- or single-stranded. In the case of a double-stranded one, it may be a double-stranded DNA, a double-stranded RNA or a hybrid of DNA:RNA. In the case of a single-stranded one, it may be sense chain (code chain) or anti-sense chain (non-code chain). Typically, the polynucleotide is a polynucleotide having base sequences represented by SEQ ID NOS: 1, 3, 5, 7, 9 and 10.
[0052] The DNA which encodes the mGluR1 variants includes in addition to the nucleotide sequence shown in SEQ ID NOS: 1, 3, 5, 7, 9 and 10, DNA which hybridizes with DNA having this nucleotide sequence or a probe that can be prepared from the same nucleotide sequence under stringent conditions and that encodes the mGluR1 variant. The “stringent conditions” means conditions whereby specific hybrid is formed but nonspecific hybrids are not formed. It is difficult to clearly express the conditions by numeric values; examples thereof include those conditions whereby DNAs having high homology, for example, DNAs having 50% or more, preferably 75% or more homology hybridize with each other but DNAs having a lower homology than that will not hybridize with each other, or those conditions whereby DNAs hybridize with each other under ordinary washing conditions in southern hybridization, i.e., at 60° C. and a salt concentration corresponding to 1×SSC, 0.1% SDS, preferably 0.1×SSC, 0.1% SDS.
[0053] Cells to which DNA encoding the mGluR1 variant is introduced include preferably animal cells, insect cells or yeast when the activity of mGluR1 variant is necessary, with animal cells being particularly preferable. Examples of cells that are considered to enable transient expression of the function by introducing a recombinant vector containing DNA encoding the mGluR1 variant include Xenopus laevis oocyte, Chinese hamster ovary (CHO) cell, baby hamster kidney (BHK) cell, human embryonic kidney (HEK) cell, Sf-9 insect cell, PC12 cell, and COCA-2 cell. In addition, when DNA encoding the mGluR1 variant is incorporated in chromosomal DNA to express the mGluR1 variant permanently, those cells other than the Xenopus laevis oocyte are suitable.
[0054] With regard to a method for introduction of DNA coding for mGluR1 variant, publicly known methods may be used. Technique which is necessary for the operations such as an operation of introduction of DNA into cells is mentioned in Sambrook, J., Fritsch, E. F. and Maniatis, T. “Molecular Cloning, A Laboratory Manual, Second Edition”, Cold Spring Harbor Laboratory Press (1989), etc.
[0055] On the other hand, when no physiological activity is necessary such as the case where the mGluR1 variant is used as an immunogen for preparing antibody that specifically binds to the mGluR1 variant, cells to which DNA encoding the mGluR1 variant is introduced may be those cells that do not express the mGluR1 variant in an active form. As such cells, microbial cells that are usually used for the production of heterologous protein, including Escherichia coli may be used.
[0056] To produce the mGluR1 variant in the host cell, DNA, which encodes the mGluR1 variant, is ligated to an expression regulation sequence such as promoter or enhancer suitable for the host cell. The DNA which encodes the mGluR1 variant may include a processing information site, for example, a ribosome binding site, an RNA splicing site, a polyadenylation site, and a transcription terminator sequence as necessary. Preferable expression control sequences include promoters derived from immunoglobulin gene, SV40, adenovirus, bovine papilloma virus, and cytomegalovirus.
[0057] The techniques necessary for the manipulation of cells such as introduction of DNA therein are described in, for example, Sambrook, J., Fritsch, E. F., and Maniatis, T., “Molecular Cloning A Laboratory Manual, Second Edition”, Cold Spring Harbor Laboratory Press, (1989).
[0058] The mGluR1 variant and a cell that retains the mGluR1 variant can be produced by cultivating a cell that harbors the DNA encoding the mGluR1 variant obtained as described above in an expressible form in a medium to produce the mGluR1 variant.
[0059] Active mGluR1 variant, that is, mGluR1 variant that can generate a second messenger when glutamic acid is bound thereto can be utilized for screening agonist, antagonist or allosteric modulator of glutamic acid. For example, the mGluR1 variant and a substance that binds to the mGluR1 variant are reacted in the presence of a test substance, and inhibition or promotion of the reaction is detected, thereby screening agonist, antagonist or allosteric modulator of glutamic acid (hereinafter, these may be referred to collectively as “ligand”). The allosteric modulator binds to a site other than the binding site between the mGluR1 variant and glutamic acid to exhibit similar function to that of the agonist or antagonist.
[0060] Further, the agonist of glutamic acid may be screened by reacting the mGluR1 variant with a test substance and detecting the reaction.
[0061] The active mGluR1 variant may include cells that express the mGluR1 variant or membrane fractions prepared from such cells. Such membrane fractions may be prepared by allowing cells to express active mGluR1 variant, ultrasonically disrupting the cells, and subjecting the sonicate to density gradient centrifugation to collect a membrane fraction.
[0062] Further, examples of the substance that binds to the above-mentioned mGluR1 variant include glutamic acid, glutamic acid agonist, or known ligands that bind to mGluR1 (L-AP4, CPPG, MAP-4, or the like). The substances that modulate the activity of the mGluR1 variant include drugs that influence the intracellular concentration of calcium (calcium channel and sodium channel opener, Na/K pump inhibitor, Na/Ca exchange agonist, Ca-ATPase inhibitor, protein kinase C agonist), drugs that influence intracellular cAMP concentration (phosphodiesterase agonist, adenylate cyclase agonist), and drugs that influence intracellular cGMP concentration (cGMP-dependent phosphodiesterase agonist, guanylate cyclase agonist) and so forth.
[0063] Inhibition or promotion of the reaction between mGluR1 variant and a substance that binds thereto can be detected by measuring a second messenger that is generated by binding of a ligand such as glutamic acid to the mGluR1 variant. Alternatively, the above-mentioned inhibition or promotion of reaction can also be detected by measuring the binding of a labeled known ligand to the mGluR1 variant instead of detecting the second messenger.
[0064] Further, the reaction between the mGluR1 variant and the agonist of glutamic acid can be detected by detecting a second messenger that is generated by binding of the mGluR1 variant to the agonist of glutamic acid.
[0065] The intracellular domain of mGluR1 variant is the same as the brain type and gustatory bud type mGluR1 and the brain type and gustatory bud type mGluR1 have the same intracellular signal transmitting mechanism. Accordingly, the above-mentioned second messenger is a rise in intracellular calcium concentration accompanied by the production of inositol triphosphate (IP3) as a result of activation of Gq (GTP binding protein) followed by activation of phospholipase C. In the downstream area of calcium variation in signal transmittance, there are function adjustment of acute stage by phosphorylation of cytoplasm and membrane protein and that by gene expression adjustment via intracellular calcium-dependent protein kinase. Therefore, it is possible to detect a second messenger other than IP3 and calcium by measurement of intracellular cAMP, cGMP changes and channel function change as a result of activation of calcium-dependent phosphodiesterase, protein phosphorylation of cell membrane fraction, etc.
[0066] Hereinafter, specific methods for searching a ligand using mGluR1 variant will be exemplified. (1) mGluR1 variant cRNA is expressed in oocytes of Xenopus and a ligand acting on mGluR1 variant is searched by a two-electrode voltage cramp method using increase or decrease in intracellular calcium-depending chloride current (Pin, J. P., et al., Proc. Natl. Acad. Sci. USA, Nov. 1, 1992;89(21):10331-5; Kasahara, J., Sugiyama, H., FEBS Lett., Nov. 21, 1994;355(1):41-4; Takahashi, K., et al., J. Biol. Chem., Sep. 15, 1993;268)26):19341-5).
[0067] (2) A candidate compound for ligand and known ligand acting on mGluR1 (such as glutamic acid, quisqualic acid, CHPG, MPEP, LY367385, etc.) are acted on a mGluR1 variant-expressing cell or a membrane fraction prepared from that cell for a certain period and amount of the known ligand bound to cell membrane of the mGluR1 variant-expressing cell or the membrane fraction is measured to conduct a ligand search (Naples, M. A., Neuropharmacology, 2001;40(2):170-7; Thomsen, C., Neuropharmacology, January 1997;36(1):21-30; H. I. Yamamura, S. J. Enna and M. J. Kuhar, eds. 1958, Neurotransmitter Receptor Binding, 2nd ed., Raven Press, New York). Amount of the known ligand is able to be measured by the amount of radioactivity bound to the cell membrane or the membrane fraction after a radioactive labeling of a part of such substances.
[0068] (3) A calcium-sensitive dye (for example, Fura-2, Indo-1, Fluo-3 or the like) is introduced into an mGluR1 variant expressing cell in advance, and a ligand candidate compound and the mGluR1 variant expressing cells are allowed to contact for a certain period of time, and then ligands are screened by using as an index a change in a ratio of intensities of fluorescence (intracellular calcium concentration). Alternatively, screening of ligand is performed by a change in a ratio of intensities of fluorescence (intercellular calcium concentration) obtained when an mGluR1 variant agonist, a candidate compound for ligand, and an mGluR1 variant expressing cells into which a calcium-sensitive dye is introduced are allowed to contact for a certain period of time.
[0069] (4) Screening of ligands is performed by using as an index a change in a ratio of intensities of fluorescence (intracellular cAMP concentration) obtained when a cAMP-sensitive fluoroprotein (for example, FICRhR or the like) is introduced into an mGluR1 variant expressing cell in advance and then a ligand candidate compound and the mGluR1 variant expressing cells are allowed to contact for a certain period of time (Adams S R, Nature Feb. 21, 1991; 349(6311): 694-7).
[0070] (5) Screening of ligands is performed by using as an index the production amount of proton obtained when a candidate compound for ligand and an mGluR1 variant expressing cells are allowed to contact for a certain period of time, or when an mGluR1 variant agonist, a candidate compound for ligand and an mGluR1 variant expressing cells are allowed to contact for a certain period of time and measured by a cytosensor (McConnell H M, Science Sep. 25, 1992; 257(5078): 1906-12).
[0071] A food additive containing agonist, antagonist or allosteric modulator of glutamic acid searched as mentioned above as an effective ingredient is able to be used as a novel umami taste-adjusting substance. Further, a pharmaceutical composition containing agonist, antagonist or allosteric modulator of glutamic acid searched as mentioned above as an effective ingredient is able to be used as a drug for the adjustment of second messenger generated by binding of glutamic acid to a glutamate receptor. When the second messenger is adjusted, it is now possible that diseases and symptoms caused by abnormality of the glutamate receptor are improved and prevented.
[0072] The anomalies of control of vagus nerve include anomaly of afferent pathway (disorder of nutrient recognition) and anomaly of efferent pathway. The diseases or pathology due to the anomaly of afferent pathway include hyperphagia, cibophobia, obesity and so on. On the other hand, those due to the anomaly of efferent pathway include digestive ulcers (stomach ulcer, duodenum ulcer) due to psychogenetic hyperphagia, cibophobia, obesity, anomaly of acid secretion, anomaly of blood flow in digestive tract, anomaly of secretion of digestive enzymes, etc., stress ulcers, drug-caused (NSAIDs, etc.) acute ulcers, ischemic ulcer (ischemic colitis), diabetes due to anomaly of secretion of insulin or anomaly of secretion of digestive tract hormone, heavy stomach, nausea, constipation, diarrhea, hypersensitivity vowel syndrome, etc. due to anomaly of motility and so forth.
[0073] Use of mGluR1 variant as an immunogen enables preparation of an antibody that specifically binds to the mGluR1 variant. In particular, since the mGluR1 variant has a novel amino acid sequence in the N-terminus, antibody, particularly monoclonal antibody, that contains this portion as an epitope is expected to bind to the mGluR1 variant and not to bind to other glutamate receptors. The antibody specific to the mGluR1 variant can be used in immunostaining specific to the mGluR1 variant. Further, when the amino acid residue of the novel N-terminal intracellular domain (cell surface exposure part) is estimated from the three-dimensional structure forecast, it is possible to prepare an mGluR1 variant-specific antibody. An antibody which is specific to mGluR1 variant is able to be used for an immunostaining which is specific to mGluR1 variant, etc.
BRIEF DESCRIPTION OF THE DRAWINGS
[0074] FIG. 1 is a graph which shows an outline of splicing of mGluR1 and mGluR1 variants (mGluRTα, mGluRTβ and mGluRTγ).
[0075] FIG. 2 is a graph which shows an outline of structures of mGluR1 and mGluR1 variants (mGluRTα, mGluRTβ and mGluRTγ).
[0076] FIG. 3A is a photograph which shows the result of immunostaining of taste bud (circumvallate papilla) of rat by an anti-mGluR1 antibody.
[0077] FIG. 3B is a photograph which shows the result of immunostaining of stomach of rat by an anti-mGluR1 antibody.
[0078] FIG. 4 is a drawing which shows the action of L-glutamic acid on vagal gastric branch-afferent nerve activity. The abscissa stands for time while the ordinate stands for nerve activity.
[0079] FIG. 5 is a drawing in which expression of nucleotide coding for mGluR1 variant by an RT-PCR method is confirmed ( FIG. 5A : mGluRTα; FIG. 5B : mGluRTβ). It has been confirmed that mGluR1 variant is expressed in taste bud.
[0080] FIG. 6 is a drawing which shows changes in membrane currency when mGluR1 variant is expressed in oocytes of Xenopus and sodium glutamate is acted thereon.
DETAILED DESCRIPTION OF THE INVENTION
[0081] The present invention will now be more specifically illustrated by way of the following Examples although the present invention is not limited thereto.
EXAMPLE 1
Cloning of Novel Metabotropic Glutamate Receptor cDNA from Circumvallate Papillae of Rat
[0082] Total RNA derived from circumvallate papillae of ten rats of Wistar strain of 16 weeks age were extracted and subjected to a reverse transcription reaction to give cDNA (kit used: SuperScript, Gibco-BRL). cDNA coding for full length of mGluR1 was used as a template and a PCR was carried out by Z-Taq. This enzyme has a good replication efficiency at 3′-side and is suitable for a TOPO TA cloning reaction after that. The PCR product was subjected to electrophoresis using 2% agarose gel and the sequences were analyzed by an ABI Sequencer Model 3100 (ABI Co., Ltd.).
[0083] In six kinds of mGluR1 variant cDNA (mGluRTαa, mGluRTαb, mGluRTβa, mGluRTβb, mGluRTγa and mGluRTγb) found from circumvallate papillae, there are unique sequences at 5′-side, and in that areas, there are stop codons. The upstream side thereof is the same as that in the known substance, and that is quite similar to the sequence of mGluR1 of type A or type B. Such a unique part is not translated; therefore, all of the six kinds of mGluR1 variant cDNA are the same as a part of amino acid sequence of mGluR1; however, the chain length is short.
[0084] Forward primers specific to the six kinds of mGluR1 variant cDNA were prepared by Hokkaido System Science (the primers used are shown in Table 1) while, with regard to reverse primers, the followings were prepared from brain type mRNA sequence (Masu, et al., Nature, 349:760, 1991) (mGluR1-4253R 5′-TAC CAT ATG GAA TTG TGC TTT GTC A-3′ (SEQ ID NO: 17) and mGluR1-4198R 5′-ATA ATT CAA GAG TCA CAA TCC TGG C-3′ (SEQ ID NO: 18) for type A and mGluR1-3266R 5′-GGG TAT TGT CCT CTT CTT CCA CA-3′ (SEQ ID NO: 19) for type B).
[0085] cDNA (150 ng) was used as a template, then 10 μM of forward and reverse primers, 10×LA PCR buffer, 2.5 mM of MgCl 2 and 2.5 mM of dNTP were mixed and 0.25 units of Z-Taq enzyme was placed therein to make the total volume 10 μl. Condition for the PCR was that GeneAmp PCR System 9700 was used where a cycle of 94° C.→20 seconds, 56° C.→1 minute and 68° C.→3 minutes was carried out for 30 cycles; finally, 10 minute extension o 68° C. was done. Further, the second PCR was conducted and the resulting template was subjected to a cloning using pCRII-TOPO vector by a TOPO TA Cloning Kit (Invitrogen). Positive clones were subjected to a colony PCR while plasmids were purified by a Hispeed Plasmid Maxi-Kit (Quiagen) followed by subjecting to a functional analysis.
[0086] As a result, novel cDNAs mentioned in SEQ ID NOS: 1, 3, 5, 7, 9 and 10 were found. The resulting clones were found to be splicing variants of mGluR1 having novel extracellular domain.
TABLE 1 Primers SEQ Name Primer Name ID NO Sequence Brain PCR-1 Forward mGluR1-50F 20 5′-GAG ACC AAT AGC TGT GTC TAC CC-3′ mGluR1a Reverse mGluR1-4253R 17 5′-TAC CAT ATG GAA TTG TGC TTT GTC A-3′ PCR-2 Forward mGluR1-114F 21 5′-TGG ACA CCT GAT CCA CAC ACC TT-3′ Reverse mGluR1-4198R 18 5′-ATA ATT CAA GAG TCA CAA TCC TGG C-3′ Brain PCR-1 Forward (same) 20 5′-GAG ACC AAT AGC TGT GTC TAC CC-3′ mGluR1b Reverse (same) 17 5′-TAC CAT ATG GAA TTG TGC TTT GTC A-3′ PCR-2 Forward (same) 21 5′-TGG ACA CCT GAT CCA CAC ACC TT-3′ Reverse (same) 18 5′-ATA ATT CAA GAG TCA CAA TCC TGG C-3′ Brain PCR-1 Forward mGluR1-718-2F 11 5′-GTG AAT CAG AGG AAG TGT TCA GA-3′ mGluRTαa Reverse mGluR1-4253R 17 5′-TAC CAT ATG GAA TTG TGC TTT GTC A-3′ PCR-2 Forward mGluR1-718-3F 12 5′-AAT GTA ACA GTC ACT GGT GCT GGG-3′ Reverse mGluR1-4198R 18 5′-ATA ATT CAA GAG TCA CAA TCC TGG C-3′ Brain PCR-1 Forward mGluR1-718-2F 11 5′-GTG AAT CAG AGG AAG TGT TCA GA-3′ mGluRTαb Reverse mGluR1-3266R 19 5′-GGG TAT TGT CCT CTT CTT CCA CA-3′ PCR-2 Forward mGluR1-718-3F 12 5′-AAT GTA ACA GTC ACT GGT GCT GGG-3′ Reverse mGluR1-3266R 19 5′-GGG TAT TGT CCT CTT CTT CCA CA-3′ Brain PCR-1 Forward mGluR1-790-1F 13 5′-GGG ACT CTC TCC TGT CTT GTG AG-3′ mGluRTβa Reverse mGluR1-4253R 17 5′-TAC CAT ATG GAA TTG TGC TTT GTC A-3′ PCR-2 Forward mGluR1-790-2F 14 5′-AGC ATA ACA GGG AAT TGC AGT GG-3′ Reverse mGluR1-4198R 18 5′-ATA ATT CAA GAG TCA CAA TCC TGG C-3 Brain PCR-1 Forward (same) 13 5′-GGG ACT CTC TCC TGT CTT GTG AG-3′ mGluRTβb Reverse (same) 17 5′-TAC CAT ATG GAA TTG TGC TTT GTC A-3′ PCR-2 Forward (same) 14 5′-AGC ATA ACA GGG AAT TGC AGT GG-3′ Reverse (same) 18 5′-ATA ATT CAA GAG TCA CAA TCC TGG C-3 Brain PCR-1 Forward mGluR1-1599-200F 15 5′-CAG ACA GAA TAT AAT AGT CGG TC-3′ mGluRTγa Reverse mGluR1-4253R 17 5′-TAC CAT ATG GAA TTG TGC TTT GTC A-3′ PCR-2 Forward mGluR1-1599-221F 16 5′-ACA AGT ACA AAA CAA GCT CTG C-3′ Reverse mGLuR1-4198R 18 5′-ATA ATT CAA GAG TCA CAA TCC TGG-C3′ Brain PCR-1 Forward (same) 15 5′-CAG ACA GAA TAT AAT AGT CGG TC-3′ mGluRTγb Reverse (same) 17 5′-TAC CAT ATG GAA TTG TGC TTT GTC A-3′ PCR-2 Forward (same) 16 5′-ACA AGT ACA AAA CAA GCT CTG C-3′ Reverse (same) 18 5′-ATA ATT CAA GAG TCA CAA TCC TGG-C3′
EXAMPLE 2
Identification of Localization of Glutamate Receptor by Immunostaining Means
[0087] <1> Preparation of slice specimen of tongue of rat Under anesthetization with ether, right auricle of heart of rat (Wistar strain; male; 10 to 15 weeks age) was incised and blooded; immediately after that, tongue site was collected.
[0088] The cut-out tongue specimen was shaken for one night and day with 4% paraformaldehyde (4° C.) and immobilized by dipping therein. After that, it was dipped for 3 to 4 days in 20% sucrose-PBS to cryoprotect, embedded in Tissue-Tek R (OCT compound) and sliced into 5 to 7 μm using a cryostat. The slices were dried at room temperature and stored at 4° C. until subjecting to staining.
[0089] <2> Immunostaining by anti-metabotropic glutamate receptor type 1 antibody
[0090] Immunostaining of the slices was carried out according to a method mentioned in Drengk, A. C., et al., J. Auto. Nerv. Sys., 78:109-112, 2000 and Miampamba, M., et al., J. Auto. Nerv. Sys. 77:140-151, 1999. After the slices were washed with PBS firstly, they were treated with 3% hydrogen peroxide methanol in order to inhibit the reaction by intrinsic peroxidase. After that, the slices were washed with PBS and were subjected to a blocking for 1 hour using 1% normal bovine serum albumin-added PBS (1% BSA-PBS) containing 10% normal equine serum. After washing with PBS once again, they were made to react with a primary antibody (anti-mGluR1a, rabbit, polyclonal, Chemicon, cat# AB 1551) diluted with 1% BSA-PBS containing 1% normal equine serum at 4° C. for two nights. Then the slices were washed with PBS and made to react with the secondary antibody (anti-mGluR1a, rabbit, polyclonal, Chemicon, cat# AB 1551) diluted with 1% BSA-PBS at room temperature for one hour. Finally, reaction with ABC (avidin-biotin complex) was carried out using a Vectorstain Elite Kit (Vector) and colorized using 0.025% diaminobenzidine-0.25% nickel chloride-0.01% H 2 O 2 . After completion of the reaction, the slices were washedwith PBS, dehydrated with ethanol-xylene, sealed and observed under a microscope. That which was not treated with a primary antibody was used as a negative control.
[0091] <3>Results
[0092] The result of the immunostaining is shown in FIG. 3 . In the tongue specimen, taste cells were stained by the anti-mGluR1 antibody ( FIG. 3A ). It has been usually believed that no mGluR1 receptor is expressed in taste cells. Therefore, it is believed that mGluR1 variant is expressed in the taste cells; and functionally, relation to the umami reception was suggested. In the stomach specimens ( FIG. 3B ), each of cell which produces viscous liquid of pylorus and main cell and auxiliary cell of stomach body was stained by the anti-mGluR1. It has been generally believed no mGluR1 receptor is expressed in those cells. Therefore, mGluR1 variant was expressed in viscous liquid producing cell and main cell, and relation to secretion of viscous liquid and secretion of digestive enzyme was suggested, functionally.
Example 3
Presumption of Function of mGluR1 Variant
[0093] Rats (Wistar strain, males, 8 to 10 weeks age; Nippon Charles Liver) were fasted for 18 hours, laparotomy was conducted under anesthetization with urethane (1 g/kg; i.p.) and vagal gastric branch was exfoliated to an extent of about 5 mm. After vagal bundle was cut, it was placed on a small operation stand (8×6 mm), fat and bonded tissues around that were carefully detached and the terminal fiber at the side of organ was placed on a dipole electrode made of platinum for recording and insulated from the surrounding tissues by a mixture of liquid paraffin-vaseline (1:1). In the meanwhile, as a route for administration of MSG (sodium L-glutamate; manufactured by Ajinomoto Co., Inc.), a silicon tube for oral administration was implanted in the stomach.
[0094] Nerve action potential was amplified to an extent of 10,000-fold by a micropotential amplifier (DAM-80 manufactured by WPI); and after noise was reduced by a Vessel filter (4-pole, High Cut 10 Hz, Low Cut 1 KHz), it was subjected to an A/D conversion (Powerlab 4sp, manufactured by ADI Instruments, Inc.) and incorporated into a computer (sampling rate 3 KHz, iBook). At the same time, an amplified signal was separated by a window discriminator (DSE-435 manufactured by Daiya Medical Co., Ltd.) into a noise component and a nerve signal component together with monitoring by an oscilloscope, integrated for 5 seconds by a spike counter (DSE-335P manufactured by Daiya Medical Co., Ltd.) and recorded in a chart recorder (WT-465G manufactured by Nippon Koden Corporation). In analysis of the spike wave shape, a SHE software (manufactured by ADI Instruments, Inc.) was used.
[0095] The result is shown in FIG. 4 . Centripetal activity of vagal gastric branch upon administration of 150 mM of MSG to stomach was accelerated. Vagal centripetal path is believed to be a signal transmittance path which sends visceral sense, particularly nutrition information from stomach and intestine, to bulbar nucleus of solitary tract and conducts digestion adjustment by after-meal sense such as satisfactory and unpleasant senses and adjustment of vagal centrifugal path. Accordingly, the fact that vagal centripetal activity was accelerated by administration of MSG to digestive tracts shows the possibility that MSG is a cause for generation of its signal and that mGluR1 variant expressed in lumen of digestive tract mediates its signal generation.
Example 4
Expression of mGluR1 Variant in Tissues by RT-PCR Method
[0000] Whole Coding Sequence
[0096] cDNA prepared by reverse transcription of total RNA of brain and circumvallate papilla with transcriptase was used. With regard to the 1st PCR primer, 30 cycles of PCR were carried out using mGluR1-790-1F (forward) (SEQ ID NO: 13), mGluR1-4253R (reverse) (SEQ ID NO: 17) and Z-Taq and the resulting PCR product diluted to an extent of 10-fold was used as a template for the 2nd PCR. For primer in the 2nd PCR, mGluR1-718-3F (forward; 5′-AAT GTA ACA GTC ACT GGT GCT GGG-3′) (SEQ ID NO: 12) and mGluR1-3266R (reverse: 5′-GGG TAT TGT CCT CTT CTT CCA CA-3′) (SEQ ID NO: 19) were used in the case of mGluRTα; while, in the case of mGluRTβ, mGluR1-790-2F (forward) (SEQ ID NO: 14) and mGluR1-4198R (reverse) (5′-ATA ATT CAA GAG TCA CAA TCC TGG C-3′) were used. That was conducted in 30 cycles as well using Z-Taq. The resulting PCR products were already confirmed by an ABI Sequencer Model 3100. Incidentally, the type of the device used for the PCR was GeneAmp PCR System 9700. As a result, bands were confirmed near 1760 bp (type A) and 1900 bp (type B) for mGluRTα; while, for mGluRTβ, a band was confirmed near 2000 bp, and the expression was confirmed in circumvallate papilla ( FIG. 5A and FIG. 5B ).
Example 5
Analysis of Function: Oocyte Isolation
[0097] Oocyte-expressing strain of Xenopus was used for analysis of function of mGluR1 mRNA derived from circumvallate papilla of rats.
[0098] Female Xenopus (purchased from Watanabe Zoshoku) was bred in a fish tank until oocytes were isolated. The Xenopus was anesthetized with tricain methanesulfonate (MS 222, Sigma) dissolved in deionized water in a concentration of 1 g/L followed by buffering with NaHCO 3 (500 mg/L). Anatomy was conducted by hand and oocytes in stages V and VI were recovered from ovary and incubated (for 30 minutes to 1 hour) in a 0.2% collagenase S-1 (Nitta Gelatin) until dissociation took place. After treating with collagenase, the oocytes were washed; follicles were removed; selection was conducted under a microscope; and incubation was carried out at 18° C. for one night.
[0000] Metabotropic Glutamate cRNA Preparation
[0099] Variant mGluR1 cDNA was constructed by an RT-PCR method from total RNA of taste papilla and brain of rat using the following primers (mGluRTβ: 1st PCR: mGluR1-790-1F 5′-GGG ACT CTC TCC TGT CTT GTG AG-3′ (SEQ ID NO: 13), mGluR1-4253R 5′-TAC CAT ATG GAA TTG TGC TTT GTC A-3′ (SEQ ID NO: 17), 2nd PCR: mGluR1 790-2F forward 5′-AGC ATA ACA GGG AAT TGC AGT GG-3′ (SEQ ID NO: 14), mGluR1 4198 reverse 5′-ATA ATT CAA GAG TCA CAA TCC TGG C-3′ (SEQ ID NO: 18), mGluRTγ: 1st PCR: mGluR1-1599-200F 5′-CAG ACA GAA TAT AAT AGT CGG TC-3′ (SEQ ID NO: 15), mGluR1-4253R 5′-TAC CAT ATG GAA TTG TGC TTT GTC A-3′ (SEQ ID NO: 17), 2nd PCR: mGluR1-1599-221F 5′-ACA AGT ACA AAA CAA GCT CTG C-3′ (SEQ ID NO: 16), mGluR1 4198 reverse 5′-ATA ATT CAA GAG TCA CAA TCC TGG C-3′ (SEQ ID NO: 18)) and constitutive enzyme Z-Taq DNA polymerase. Since the polymerase remains blunt end in PCR fragments, PCR-amplified mGluRTβa and mGluRTγa template DNA were inserted into pCRII-TOPO vector (Invitrogen) by a TOPO-TA cloning reaction. pCRII-TOPO/mGluRTγ vector and pCRII-TOPO/mGluRTβ vector were made into straight lines using EcoRV and XbaI, respectively, extracted with a mixture of phenol and chloroform and precipitated with ethanol together with sodium acetate. After a sequence analysis, cRNA was prepared using a transcription kit for Sp6 promoter made by Ambion (mMESSAGE MMACHINE kit) binding to pCRII-TOPO promoter. Briefly, transcription of straight-chain template DNA of about 1 μg was carried out using 2 μL of enzyme mixture (the final concentration was made 20 μL volume using 10 μL of 2XNTP/Cap and 10× reaction buffer). For the synthesis of cRNA, the reaction solution was incubated at 37° C. for 3 hours and the residual template was decomposed by addition of 1 μL of DNase 1 for 15 minutes. The transcribed product was purified by extracting with phenol-chloroform and precipitating with isopropanol. cRNA was reconstructed in water treated with diethylpyrocarboxylic acid; and before injecting into oocytes, quantitative determination was conducted under irradiation with UV.
[0000] Microinjection of cRNA
[0100] After 24 hours from the recovery, 100 ng of mRNA per 25 nL of glass capillary tube having a standard diameter of 12 μm (Microinjector, WPI) was injected into oocytes of healthy Xenopus having transparent animal pole and vegetal pole. Incubation was carried out for 72 hours in an MBS solution [88 mM NaCl, 1 mM KCl, 2.4 mM NaHCO 3 , 10 mM HEPES, 0.82 mM MgSO 4 , 0.33 mM Ca(NO 3 ) 2 and 0.91 mM CaCl 2 ; pH 7.5] to which 2 mM pyruvic acid and 0.5 mM theophylline were added; and after that, the oocytes were used for an electrophysiological assay (Sanna, et al., 1994).
[0000] Method for Measurement of Membrane Current
[0101] Membrane current of oocytes was measured by a two-electrode membrane potential fixation method using Geneclamp Amplifier (Axon Instruments). Glass microelectrode used for the measurement was prepared by a puller (Shutter Co., Ltd.) and that where electrode resistance upon filling with 3M KCl was 1 to 3 MΩ was used. The treated oocytes were transferred to a chamber for the measurement; glass electrode was inserted under a stereoscopic microscope; and under fixation of potential to −70 mV, calcium-dependent chloride current upon stimulation with glutamic acid was measured. The experiment was carried out for both of the cases of cells which express mGluR1 variant of rat and which do not.
[0102] The result of record of measurement of membrane current of oocytes where mGluRTβa was expressed is shown in FIG. 6 . When the medium in an inner area of the measuring bath was substituted with a medium containing 50 mM of sodium glutamate (MSG), continuous introvert current was induced and the introvert current was confirmed to disappear by performing substitution of the medium again. That is believed to be due to the fact that glutamic acid acted on the receptor whereupon a calcium-dependent chloride channel via an intracellular information transmittance system was activated; and as a result, that was measured as introvert current. The same introvert current was also observed in mGluRTγa-expressing oocytes. Incidentally, although not shown here, such a reaction was not observed in oocytes into which cRNA was not injected. Therefore, it has now been proved that the mGluR1 variant which is a cloning gene product of the present invention has an action of conducting the glutamic acid reception and inducing an intracellular calcium mobilization. According to the same proceeding, it has been also confirmed that mGluRTα has a ligand action and it is also possible to search agonist, antagonist or allosteric modulator.
INDUSTRIAL APPLICABILITY
[0103] In accordance with the present invention, there is provided a novel metabotropic glutamate receptor. This glutamate receptor is able to be used for the search of agonist, antagonist or allosteric modulator for glutamic acid. It is also able to be used as a food additive as a novel umami-tasting substance and also as a drug for improving diseases and symptoms caused by metabolism abnormality in digestive tracts.
[0104] The invention being thus described, it will be obvious that the same may be modified or varied in many ways. Such modifications and variations are not to be regarded as a departure from the spirit and scope of the invention and all such modifications and variations are intended to be included within the scope of the following claims. | It is intended to disclose a glutamate sensor in taste sensation and digestion and provide techniques using the same. A glutamate-receptor protein having the following characteristics is reacted with a substance binding thereto in the presence of a test substance and thus the inhibition or acceleration of the reaction is detected to thereby search for a glutamate agonist or antagonist or an allosteric modulator: (1) having a transmembrane domain and an intracellular domain common to a type 1 metabolic glutamate receptor protein; and (2) having an extracellular domain shorter by about 409 or 481 amino acid residues than the type 1 metabolic glutamate receptor protein. | 2 |
FIELD OF THE INVENTION
[0001] The present invention relates to a method and device for removing metals, amines, and other contaminants from crude oil and, more particularly, to a method for use in an oil refinery and to an oil refinery for employing such methods.
BACKGROUND INFORMATION
[0002] U.S. Publication No. 2004/0045875 discloses a method for transferring metals and/or amines from a hydrocarbon phase to a water phase in an oil refinery desalting process. The method consists of adding to a wash water an effective amount of a composition comprising certain water-soluble hydroxyacids to transfer metals and/or amines from a hydrocarbon phase to a water phase. The water-soluble hydroxyacid is selected from the group consisting of glycolic acid, gluconic acid, C.sub.2-C.sub.4 alpha-hydroxyacids, malic acid, lactic acid, poly-hydroxy carboxylic acids, thioglycolic acid, chloroacetic acid, polymeric forms of the above hydroxyacids, poly-glycolic esters, glycolate ethers, ammonium salt and alkali metal salts of these hydroxyacids, and mixtures thereof. The pH of the wash water is lowered to 6 or below, before, during and/or after adding the composition and the wash water is added to crude oil to create an emulsion. Finally, the emulsion is resolved into the hydrocarbon phase and an aqueous phase using electrostatic coalescence, where at least a portion of the metals and/or amines are transferred to the aqueous phase.
[0003] Optimum Temperature in the Electrostatic Desalting of Maya Crude Oil by Pruneda et al published in the 2005 Journal of the Mexican Chemical Society discloses a simulation model which suggests that there is an optimum temperature to maximize economic benefit when desalting heavy crude oil. As indicated in the art, an increase in process temperature has two effects to be considered. First, as temperature is increased, there is a corresponding decrease in oil density and viscosity which implies a significant increase in the settling rate of water droplets within the oil phase thus allowing a greater amount of oil to be processed resulting in an increase in profit from performing oil desalting. However, crude oil conductivity increases exponentially with temperature which implies a higher rate of electrical power consumption during electrostatic coalescence which increases processing expense.
[0004] U.S. Publication No. 2004/0045875 and Optimum Temperature in the Electrostatic Desalting of Maya Crude Oil by Pruneda et al are hereby incorporated by reference herein.
SUMMARY OF THE INVENTION
[0005] U.S. Publication No. 2004/0045875 describes an Electrostatic Desalting Dehydration Apparatus (EDDA) as a laboratory test device, but does not disclose actual electrostatic coalescence in an oil refinery desalting process.
[0006] The crude oil temperature, the electric field intensity, the electric voltage waveform used to create the electric field, crude oil feed rate, wash water rate/quality/flow configuration, the control of the water level and emulsion layer, the hydroxyacid addition rate, et al are very important factors that affect refinery desalter performance. As per the present invention, control of these factors to perform electrostatic coalescence when forming the emulsions disclosed in the US 2004/0045875 publication can be especially important.
[0007] The present invention provides a method for removing calcium, other metals, and amines from crude oil in a refinery desalting process comprising the steps of:
[0008] adding a wash water to the crude oil;
[0009] adding the wash water to the crude oil to create an emulsion;
[0010] adding to the wash water or the emulsion at least one water-soluble hydroxyacid selected from the group consisting of glycolic acid, gluconic acid, C.sub.2-C.sub.4 alpha-acids, malic acid, lactic acid, poly-hydroxy carboxylic acids, thioglycolic acid, hydroxy chloroacetic acid, polymeric forms of the above hydroxyacids, poly-glycolic esters, glycolate ethers, and ammonium slat and alkali metal salts of these hydroxyacids, and mixtures thereof;
[0011] heating at least one of the crude oil, the wash water or the emulsion to a desired temperature;
[0012] resolving the emulsion containing the water-soluble hydroxyacid into a hydrocarbon phase and an aqueous phase using electrostatic coalescence, the metals and amines being transferred to the aqueous phase;
[0013] measuring a concentration of the metal or amine impurities in the hydrocarbon and/or aqueous phase; and
[0014] altering a characteristic of the desalting process to maintain residual impurity levels within the desalted crude as a function of the measured concentration.
[0015] The present invention advantageously allows for the adjustment of the crude oil feed rate, the crude oil temperature, the wash water feed rate, the wash water and additive solution mix, the temperature of the oil/wash water emulsion, the electrostatic desalter water level, the addition rate of hydroxyacid additive, and the electric field generated within the electrostatic desalter either individually or in combination as a function of metal and/or amine removal process.
[0016] The wash water preferably has a pH of 6 or below and most preferably a pH of 2 to 4.
[0017] The present invention also provides a single stage and dual stage electrostatic desalting mechanism applicable to a crude oil refinery. The common elements of each mechanism comprising;
[0018] a crude oil supply for storing crude oil;
[0019] a wash water supply for supplying wash water to the crude oil to form an emulsion;
[0020] a water-soluble hydroxyacid supply for supplying water-soluble hydroxyacid to the wash water or the emulsion;
[0021] a heater for changing the temperature of the crude oil, the wash water or the emulsion;
[0022] pumps and valves for controlling fluid flow in the desalting process; and
[0023] a controller for monitoring, controlling, and varying a characteristic of the desalting operation as a function of the concentration of metal and/or amine impurities in the aqueous phase and/or the hydrocarbon phase.
[0024] The characteristic may be, for example, the crude oil feed rate, the crude oil temperature, the wash water feed rate, the wash water and hydroxyacid additive solution mix, the temperature of the oil/wash water emulsion, the electrostatic desalter water level, the addition rate of hydroxyacid additive, the voltage level applied to the electrostatic desalter, the voltage waveform applied to the electrostatic desalter, current limits (if any) on the electrical power supply, or any combination of these.
BRIEF DESCRIPTION OF THE DRAWINGS
[0025] FIG. 1 shows a block diagram of a typical single stage crude oil electrostatic desalting mechanism according to one embodiment of the present invention;
[0026] FIG. 2 shows a block diagram of a typical first stage dehydration followed by a second stage electrostatic desalting mechanism according to one embodiment of the present invention;
[0027] FIG. 3 shows a block diagram of a typical two stage electrostatic desalting mechanism according to one embodiment of the present invention;
[0028] FIG. 4 shows a measurement and control diagram of one embodiment of the method of the present invention for a typical crude oil electrostatic desalting operation;
DETAILED DESCRIPTION
[0029] FIG. 1 shows a diagram of a single stage crude oil electrostatic desalting mechanism 1000 of the present invention.
[0030] The desalting mechanism 1000 of the present invention includes a crude oil supply 10 for storing crude oil. The crude oil supply 10 is connected to a controllable pump 70 which is connected to an optional controllable fluid mixer 80 . The optional controllable fluid mixer 80 allows an emulsion of crude oil 10 , wash water 20 , and hydroxyacid additive 30 to be created prior to heating based upon the specific characteristics of the crude oil supply 10 to be desalted. The optional controllable fluid mixer 80 , if necessary to process the crude oil supply 10 , is controlled by the controller 110 to create and maintain the proper emulsion mix of crude oil 10 , wash water 20 , and hydroxyacid additive 30 .
[0031] Following either the controllable pump 70 or the optional controllable fluid mixer 80 is a controllable flow control valve (FCV) 120 . The controllable flow control valve 120 and the controllable pump 70 work in conjunction under command of the controller 110 to control and maintain the crude oil feed rate and pressure. The crude oil 10 or crude oil emulsion created via optional controllable fluid mixer 80 is then heated to a desired processing temperature by the heater 130 which is controlled by controller 110 .
[0032] The desalting mechanism 1000 of the present invention also includes a wash water supply 20 and a hydroxyacid additive supply 30 for supplying water-soluble hydroxyacid. In the embodiment of FIG. 1 , as is preferred, the hydroxyacid additive 30 is mixed with the wash water 20 by the controllable fluid mixer 40 before the crude oil/wash water emulsion is formed. Alternatively, the hydroxyacid additive 30 could be mixed with the wash water 20 and crude oil 10 during the emulsion creation or after emulsion creation. The fluid mixer 40 is controlled by the controller 110 to create and maintain the proper solution mixture of hydroxyacid additive 30 and wash water 20 . The hydroxyacid additive 30 can be selected from the group consisting of glycolic acid, gluconic acid, C.sub.2-C.sub.4 alpha-hydroxy acids, malic acid, lactic acid, poly-hydroxy carboxylic acids, thioglycolic acid, chloroacetic acid, polymeric forms of the above hydroxyacids, poly-glycolic esters, glycolate ethers, and ammonium slat and alkali metal salts of these hydroxyacids, and mixtures thereof. Most preferably, malic acid is used.
[0033] After mixing the solution of hydroxyacid additive 30 and wash water 20 with the controllable fluid mixer 40 , the resulting solution is input to a controllable flow control valve 90 which is used to allow samples of the mixed hydroxyacid additive 30 and wash water 20 solution to be measured at a measurement station 200 . Measurements made on the solution samples would include but not be limited to solution pH, solution impurity levels, and percentage of hydroxyacid additive 30 to wash water 20 . This information is sent to the controller 110 .
[0034] After mixing the solution of hydroxyacid additive 30 and wash water 20 with the controllable fluid mixer 40 , the resulting solution is also input to a controllable pump 50 whose output is connected to a controllable flow control valve 60 . The controllable pump 50 and the flow control valve 60 work in conjunction under the command of the controller 110 to control and maintain the wash water/hydroxyacid solution feed rate and pressure. In the embodiment of FIG. 1 , the controllable flow control valve 60 is shown to be a three-way valve to allow for emulsion creation with the crude oil supply 10 via the optional controllable fluid mixer 80 , the optional controllable fluid mixer 140 , or both. Like the optional controllable fluid mixer 80 , the optional controllable fluid mixer 140 , if necessary to process the crude oil supply 10 , is controlled by the controller 110 to create and maintain the proper emulsion mix of crude oil 10 , wash water 20 , and hydroxyacid additive 30 . The controllable flow control valve 60 also allows for the hydroxyacid additive 30 and wash water 20 solution to be presented to the optional controllable fluid mixer 80 and optional controllable fluid mixer 140 at the same or different flow rates when both mixer devices are used in the desalting process.
[0035] Following the optional controllable fluid mixer 140 , the emulsion passes through a pressure control valve 160 before entering the electrostatic desalter 170 . The electrostatic desalter 170 includes a liquid level sensor (LS) 210 used to measure the aqueous level in the electrostatic desalter 170 . In the embodiment of FIG. 1 , the measurement output of the liquid level sensor 210 is routed to the controller 110 . The controller 110 uses the liquid level measurement data to control the controllable flow control valve 220 to drain the effluent from the electrostatic desalter 170 and control the aqueous layer and emulsion layer within the electrostatic desalter 170 . Alternatively, the liquid level sensor 210 output may be directly connected to a level control valve instead of the controllable flow control valve 220 to drain the effluent. The controllable flow control valve 220 is also configured to allow samples of the effluent solution to be measured at a measurement station 200 . Measurements made on the solution samples would include but not be limited to solution pH, solution impurity levels, temperature, and amount of residual oil present in the effluent. This information is sent to the controller 110 .
[0036] The electrical power supply 150 provides the voltage necessary to create the electric field necessary for electrostatic coalescence in the electrostatic desalter 170 . The controller 110 controls the electrical power supply 150 output. The electrical power supply 150 output may be static (i.e. constant voltage with a current limit) or, preferably, able to change key parameters to enhance the desalting operation. The electrical power supply 150 under the control of the controller 110 would preferably be able to alter its' output to include but not be limited to changes in the voltage level applied to the electrostatic desalter 170 , the voltage waveform applied to the electrostatic desalter 170 , current limits (if any) on the electrical power supply 150 , or any combination thereof.
[0037] The desalted crude output of the electrostatic desalter 170 passes through a pressure control valve 180 and a controllable flow control valve 190 . The controllable flow control valve 190 has two outputs to direct the desalted crude oil. Under control of the controller 110 , the controllable flow control valve 190 controls and maintains the flow rate of desalted crude oil to the remaining refinery operations. Additionally, under control of the controller 110 , the controllable flow control valve 190 can also direct samples of the desalted crude to the measurement station 200 . Measurements made on the solution samples would include but not be limited to impurity levels, temperature, residual hydroxyacid additive 30 and wash water 20 solution, etc. This information is sent to the controller 110 .
[0038] In the embodiment of FIG. 1 , the controller 110 takes measurements including but not limited to the various points described herein to evaluate the efficiency of the desalting mechanism 1000 . Based upon the type of crude oil being processed, the controller 110 can adjust various factors of the desalting operation including but not limited to the following:
[0039] The crude oil supply 10 feed rate through the controllable pump 70 and controllable flow control valve 120
[0040] The temperature of the crude oil supply 10 or, optionally, the emulsion created by mixing the crude oil supply 10 with a solution comprising the hydroxyacid additive 30 and wash water 20 through the controllable heater 130 .
[0041] The solution mixture of hydroxyacid additive 30 and wash water 20 through the controllable fluid mixer 40 .
[0042] The flow rate of the solution mixture of hydroxyacid additive 30 and wash water 20 through the controllable pump 50 and controllable flow control valve 60 .
[0043] The emulsion formation through optional controllable fluid mixer 80 and/or optional controllable fluid mixer 140 .
[0044] The electrostatic desalter 170 electric field through the controllable electrical power supply 150 .
[0045] Control of the electrostatic desalter water level and emulsion layers through the liquid level sensor 210 , the controllable flow control valve 220 , and the controllable flow control valve 190 .
[0046] As different crude oils are processed by the desalting mechanism 1000 , the characteristics necessary to efficiently desalt the crude oil will require some adjustment. Additionally, differences in electrostatic desalter 170 characteristics, wash water supply 20 purity, etc. between different desalting mechanisms 1000 require the storage of different control settings. The memory/data storage 100 function of the desalting mechanism 1000 allows the controller to access and update, if required, the control settings required to efficiently process various types of crude oil supplies 10 . Preferably, the control settings are determined based upon maximizing the economic benefit for the desalting the crude oil supply 10 . A setpoint residual impurity level for the desalted crude can be determined and the process run to maintain the impurity level below the setpoint.
[0047] FIG. 2 shows a diagram of a typical first stage dehydration followed by a second stage electrostatic desalting mechanism 2000 of the present invention.
[0048] The desalting mechanism 2000 of the present invention includes a crude oil supply 2010 for storing crude oil. The crude oil supply 2010 is connected to a controllable pump 2070 whose output is connected to a controllable flow control valve (FCV) 2120 . The controllable flow control valve 2120 and the controllable pump 2070 work in conjunction under command of the controller 2110 to control and maintain the crude oil feed rate and pressure. The crude oil 2010 is then heated to a desired processing temperature by the heater 2130 which is controlled by controller 2110 . In the embodiment of FIG. 2 , the heated crude oil passes through a pressure control valve 2160 before entering the dehydration mechanism 2310 . The dehydration mechanism 2310 is designed to remove high salinity water from the crude oil supply 2010 . The dehydration process relies on establishing a varying high voltage electric field in the oil phase of the dehydration mechanism 2310 . Due to the action of the imposed electric field, the droplets are agitated causing the drops to coalesce into droplets of sufficient size to migrate via gravity to the lower water phase of the dehydration mechanism 2310 . The dehydration mechanism 2310 includes a liquid level sensor (LS) 2340 used to measure the water level in the dehydration mechanism 2310 . In the embodiment of FIG. 2 , the measurement output of the liquid level sensor 2340 is routed to the controller 2110 . The controller 2110 uses the liquid level measurement data to control the controllable flow control valve 2330 to drain the waste water from the dehydration mechanism 2310 and control the water layer and oil layer within the dehydration mechanism 2310 . Alternatively, the liquid level sensor 2340 output may be directly connected to a level control valve instead of the controllable flow control valve 2330 to drain the waste water. The controllable flow control valve 2330 is also configured to allow samples of the effluent solution to be measured at a measurement station 2200 . Measurements made on the solution samples would include but not be limited to solution pH, solution impurity levels, temperature, and amount of residual oil present in the waste water. This information is sent to the controller 2110 .
[0049] The electrical power supply 2300 provides the voltage necessary to create the electric field necessary for water coalescence in the dehydration mechanism 2310 . The controller 2110 controls the electrical power supply 2300 output. The electrical power supply 2300 output may be static (i.e. constant voltage with a current limit) or, preferably, able to change key parameters to enhance the dehydration operation. The electrical power supply 2300 under the control of the controller 2110 would preferably be able to alter its' output to include but not be limited to changes in the voltage level applied to the dehydration mechanism 2310 , the voltage waveform applied to the dehydrator, current limits (if any) on the electrical power supply 2300 , or any combination thereof.
[0050] The crude output of the dehydration mechanism 2310 passes through a pressure control valve 2320 on its way to the controllable fluid mixer 2350 . The controllable fluid mixer 2350 allows an emulsion of crude oil 2010 , wash water 2020 , and hydroxyacid additive 2030 to be created based upon the specific characteristics of the crude oil supply 2010 to be desalted. The controllable fluid mixer 2350 is controlled by the controller 2110 to create and maintain the proper emulsion mix of crude oil 2010 , wash water 2020 , and hydroxyacid additive 2030 .
[0051] The desalting mechanism 2000 of the present invention also includes a wash water supply 2020 and a hydroxyacid additive supply 2030 for supplying water-soluble hydroxyacid. In the embodiment of FIG. 2 , as is preferred, the hydroxyacid additive 2030 is mixed with the wash water 2020 by the controllable fluid mixer 2040 before the crude oil/wash water emulsion is formed. Alternatively, the hydroxyacid additive 2030 could be mixed with the wash water 2020 and crude oil 2010 during the emulsion creation or after emulsion creation. The fluid mixer 2040 is controlled by the controller 2110 to create and maintain the proper solution mixture of hydroxyacid additive 2030 and wash water 2020 . The hydroxyacid additive 2030 can be selected from the group consisting of glycolic acid, gluconic acid, C.sub.2-C.sub.4 alpha-hydroxy acids, malic acid, lactic acid, poly-hydroxy carboxylic acids, thioglycolic acid, chloroacetic acid, polymeric forms of the above hydroxyacids, poly-glycolic esters, glycolate ethers, and ammonium slat and alkali metal salts of these hydroxyacids, and mixtures thereof.
[0052] After mixing the solution of hydroxyacid additive 2030 and wash water 2020 with the controllable fluid mixer 2040 , the resulting solution is input to a controllable flow control valve 2090 which is used to allow samples of the mixed hydroxyacid additive 2030 and wash water 2020 solution to be measured at a measurement station 2200 . Measurements made on the solution samples would include but not be limited to solution pH, solution impurity levels, and percentage of hydroxyacid additive 2030 to wash water 2020 . This information is sent to the controller 2110 .
[0053] After mixing the solution of hydroxyacid additive 2030 and wash water 2020 with the controllable fluid mixer 2040 , the resulting solution is also input to a controllable pump 2050 whose output is connected to a controllable flow control valve 2060 . The controllable pump 2050 and the flow control valve 2060 work in conjunction under the command of the controller 2110 to control and maintain the wash water/hydroxyacid solution feed rate and pressure. The output of the flow control valve 2060 is an input to the controllable fluid mixer 2350 where the emulsion of crude oil 2010 , wash water 2020 , and hydroxyacid additive 2030 is formed.
[0054] After mixing the crude oil 2010 , hydroxyacid additive 2030 , and wash water 2020 in the controllable fluid mixer 2350 , the resulting emulsion passes through a controllable flow control valve 2360 before entering the electrostatic desalter 2170 . The controllable flow control valve 2360 , under command of the controller 2110 , controls the flow rate of the crude oil emulsion into the electrostatic desalter 2170 as well as allowing samples of the emulsion to be directed to the measurement station 2200 . Measurements made on the solution samples would include but not be limited to impurity levels, temperature, amount of hydroxyacid additive 2030 and wash water 2020 solution, etc. This information is sent to the controller 2110 .
[0055] The electrostatic desalter 2170 includes a liquid level sensor (LS) 2210 used to measure the aqueous level in the electrostatic desalter 2170 . In the embodiment of FIG. 2 , the measurement output of the liquid level sensor 2210 is routed to the controller 2110 . The controller 2110 uses the liquid level measurement data to control the controllable flow control valve 2220 to drain the effluent from the electrostatic desalter 2170 and control the aqueous layer and emulsion layer within the electrostatic desalter 2170 . Alternatively, the liquid level sensor 2210 output may be directly connected to a level control valve instead of the controllable flow control valve 2220 to drain the effluent. The controllable flow control valve 2220 is also configured to allow samples of the effluent solution to be measured at a measurement station 2200 . Measurements made on the solution samples would include but not be limited to solution pH, solution impurity levels, temperature, and amount of residual oil present in the effluent. This information is sent to the controller 2110 .
[0056] The electrical power supply 2150 provides the voltage necessary to create the electric field necessary for electrostatic coalescence in the electrostatic desalter 2170 . The controller 2110 controls the electrical power supply 2150 output. The electrical power supply 2150 output may be static (i.e. constant voltage with a current limit) or, preferably, able to change key parameters to enhance the desalting operation. The electrical power supply 2150 under the control of the controller 2110 would preferably be able to alter its' output to include but not be limited to changes in the voltage level applied to the electrostatic desalter 2170 , the voltage waveform applied to the electrostatic desalter 2170 , current limits (if any) on the electrical power supply 2150 , or any combination thereof.
[0057] The desalted crude output of the electrostatic desalter 2170 passes through a pressure control valve 2180 and a controllable flow control valve 2190 . The controllable flow control valve 2190 has two outputs to direct the desalted crude oil. Under control of the controller 2110 , the controllable flow control valve 2190 controls and maintains the flow rate of desalted crude oil to the remaining refinery operations. Additionally, under control of the controller 2110 , the controllable flow control valve 2190 can also direct samples of the desalted crude to the measurement station 2200 . Measurements made on the solution samples would include but not be limited to impurity levels, temperature, residual hydroxyacid additive 2030 and wash water 2020 solution, etc. This information is sent to the controller 2110 .
[0058] In the embodiment of FIG. 2 , the controller 2110 takes measurements including but not limited to the various points described herein to evaluate the efficiency of the desalting mechanism 2000 . Based upon the type of crude oil being processed, the controller 2110 can adjust various factors of the desalting operation including but not limited to the following:
[0059] The crude oil supply 2010 feed rate through the controllable pump 2070 and controllable flow control valve 2120
[0060] The temperature of the crude oil supply 2010 through the controllable heater 2130 .
[0061] Control of the dehydration mechanism 2310 water level and oil layers through the liquid level sensor 2340 , the controllable flow control valve 2330 , and the controllable flow control valve 2360 .
[0062] The dehydration mechanism 2310 electric field through the controllable power supply 2300 .
[0063] The solution mixture of hydroxyacid additive 2030 and wash water 2020 through the controllable fluid mixer 2040 .
[0064] The flow rate of the solution mixture of hydroxyacid additive 2030 and wash water 2020 through the controllable pump 2050 and controllable flow control valve 2060 .
[0065] The emulsion formation through controllable fluid mixer 2350 .
[0066] The electrostatic desalter 2170 electric field through the controllable electrical power supply 2150 .
[0067] Control of the electrostatic desalter 2170 water level and emulsion layers through the liquid level sensor 2210 , the controllable flow control valve 2220 , and the controllable flow control valve 2190 .
[0068] As different crude oils are processed by the desalting mechanism 2000 , the characteristics necessary to efficiently desalt the crude oil will require some adjustment. Additionally, differences in dehydration mechanism 2310 characteristics, electrostatic desalter 2170 characteristics, wash water supply 2020 purity, etc between different desalting mechanisms 2000 require the storage of different control settings. The memory/data storage 2100 function of the desalting mechanism 2000 allows the controller to access and update, if required, the control settings required to efficiently process various types of crude oil supplies 2010 . Preferably, the control settings are determined based upon maximizing the economic benefit for the desalting the crude oil supply 2010 .
[0069] FIG. 3 shows a diagram of a typical two stage electrostatic desalting mechanism 3000 of the present invention.
[0070] The desalting mechanism 3000 of the present invention includes a crude oil supply 3010 for storing crude oil. The crude oil supply 3010 is connected to a controllable pump 3070 whose output is connected to a controllable flow control valve (FCV) 3120 . The controllable flow control valve 3120 and the controllable pump 3070 work in conjunction under command of the controller 3110 to control and maintain the crude oil feed rate and pressure. The crude oil 3010 is heated to a desired processing temperature by the heater 3130 which is controlled by controller 3110 . In the embodiment of FIG. 3 , the heated crude oil is mixed with recycled effluent from the electrostatic desalter 3170 to create an emulsion mix of the crude oil supply 3010 and recycled effluent from the electrostatic deslater 3170 via the controllable fluid mixer 3380 . Use of an effluent recycle as indicated in FIG. 3 is well-known in the art. The crude oil/effluent recycle emulsion passes through a pressure control valve 3160 before entering the electrostatic desalter 3310 . The electrostatic desalter 3310 includes a liquid level sensor (LS) 3340 used to measure the aqueous level in the electrostatic desalter 3310 . In the embodiment of FIG. 3 , the measurement output of the liquid level sensor 3340 is routed to the controller 3110 . The controller 3110 uses the liquid level measurement data to control the controllable flow control valve 3330 to drain the waste effluent from the electrostatic desalter 3310 and control the aqueous layer and emulsion layer within the electrostatic desalter 3310 . Alternatively, the liquid level sensor 3340 output may be directly connected to a level control valve instead of the controllable flow control valve 3330 to drain the waste effluent. The controllable flow control valve 3330 is also configured to allow samples of the waste effluent solution to be measured at a measurement station 3200 . Measurements made on the solution samples would include but not be limited to solution pH, solution impurity levels, temperature, and amount of residual oil present in the waste effluent. This information is sent to the controller 3110 .
[0071] The electrical power supply 3300 provides the voltage necessary to create the electric field necessary for electrostatic coalescence in the electrostatic desalter 3310 . The controller 3110 controls the electrical power supply 3300 output. The electrical power supply 3300 output may be static (i.e. constant voltage with a current limit) or, preferably, able to change key parameters to enhance the electrostatic coalescence operation. The electrical power supply 3300 under the control of the controller 3110 would preferably be able to alter its' output to include but not be limited to changes in the voltage level applied to the electrostatic desalter 3310 , the voltage waveform applied to the desalter, current limits (if any) on the electrical power supply 3300 , or any combination thereof.
[0072] The crude output of the electrostatic desalter 3310 passes through a pressure control valve 3320 on its way to the controllable fluid mixer 3350 . The controllable fluid mixer 3350 allows a second emulsion of electrostatic desalter 3310 output, wash water 3020 , and hydroxyacid additive 3030 to be created based upon the specific characteristics of the crude oil supply 3010 to be desalted. The controllable fluid mixer 3350 is controlled by the controller 3110 to create and maintain the proper emulsion mix of crude oil 3010 , wash water 3020 , and hydroxyacid additive 3030 .
[0073] The desalting mechanism 3000 of the present invention also includes a wash water supply 3020 and a hydroxyacid additive supply 3030 for supplying water-soluble hydroxyacid. In the embodiment of FIG. 3 , as is preferred, the hydroxyacid additive 3030 is mixed with the wash water 3020 by the controllable fluid mixer 3040 before the crude oil/wash water emulsion is formed. Alternatively, the hydroxyacid additive 3030 could be mixed with the wash water 3020 and crude oil 3010 during the emulsion creation or after emulsion creation. The fluid mixer 3040 is controlled by the controller 3110 to create and maintain the proper solution mixture of hydroxyacid additive 3030 and wash water 3020 . The hydroxyacid additive 3030 can be selected from the group consisting of glycolic acid, gluconic acid, C.sub.2-C.sub.4 alpha-hydroxy acids, malic acid, lactic acid, poly-hydroxy carboxylic acids, thioglycolic acid, chloroacetic acid, polymeric forms of the above hydroxyacids, poly-glycolic esters, glycolate ethers, and ammonium slat and alkali metal salts of these hydroxyacids, and mixtures thereof.
[0074] After mixing the solution of hydroxyacid additive 3030 and wash water 3020 with the controllable fluid mixer 3040 , the resulting solution is input to a controllable flow control valve 3090 which is used to allow samples of the mixed hydroxyacid additive 3030 and wash water 3020 solution to be measured at a measurement station 3200 . Measurements made on the solution samples would include but not be limited to solution pH, solution impurity levels, and percentage of hydroxyacid additive 3030 to wash water 3020 . This information is sent to the controller 3110 .
[0075] After mixing the solution of hydroxyacid additive 3030 and wash water 3020 with the controllable fluid mixer 3040 , the resulting solution is also input to a controllable pump 3050 whose output is connected to a controllable flow control valve 3060 . The controllable pump 3050 and the flow control valve 3060 work in conjunction under the command of the controller 3110 to control and maintain the wash water/hydroxyacid solution feed rate and pressure. The output of the flow control valve 3060 is an input to the controllable fluid mixer 3350 where the second emulsion of electrostatic desalter 3310 output, wash water 3020 , and hydroxyacid additive 3030 is formed.
[0076] After mixing the second emulsion in the controllable fluid mixer 3350 , the second emulsion passes through a controllable flow control valve 3360 before entering the electrostatic desalter 3170 . The controllable flow control valve 3360 , under command of the controller 3110 , controls the flow rate of the second emulsion into the electrostatic desalter 3170 as well as allowing samples of the emulsion to be directed to the measurement station 3200 . Measurements made on the solution samples would include but not be limited to impurity levels, temperature, amount of hydroxyacid additive 3030 and wash water 3020 solution, etc. This information is sent to the controller 3110 .
[0077] The electrostatic desalter 3170 includes a liquid level sensor (LS) 3210 used to measure the aqueous level in the electrostatic desalter 3170 . In the embodiment of FIG. 3 , the measurement output of the liquid level sensor 3210 is routed to the controller 3110 . The controller 3110 uses the liquid level measurement data to control the controllable flow control valve 3220 to recycle the effluent from the electrostatic desalter 3170 and control the aqueous layer and emulsion layer within the electrostatic desalter 3170 . Alternatively, the liquid level sensor 3210 output may be directly connected to a level control valve instead of the controllable flow control valve 3220 to recycle the effluent. The controllable flow control valve 3220 along with the controllable pump 3370 , under command of the controller 3110 , control and maintain the recycled effluent flow rate and pressure to the controllable mixer 3380 . The controllable flow control valve 3220 is also configured to allow samples of the effluent solution to be measured at a measurement station 3200 . Measurements made on the solution samples would include but not be limited to solution pH, solution impurity levels, temperature, and amount of residual oil present in the effluent. This information is sent to the controller 3110 .
[0078] The electrical power supply 3150 provides the voltage necessary to create the electric field necessary for electrostatic coalescence in the electrostatic desalter 3170 . The controller 3110 controls the electrical power supply 3150 output. The electrical power supply 3150 output may be static (i.e. constant voltage with a current limit) or, preferably, able to change key parameters to enhance the desalting operation. The electrical power supply 3150 under the control of the controller 3110 would preferably be able to alter its' output to include but not be limited to changes in the voltage level applied to the electrostatic desalter 3170 , the voltage waveform applied to the electrostatic desalter 3170 , current limits (if any) on the electrical power supply 3150 , or any combination thereof.
[0079] The desalted crude output of the electrostatic desalter 3170 passes through a pressure control valve 3180 and a controllable flow control valve 3190 . The controllable flow control valve 3190 has two outputs to direct the desalted crude oil. Under control of the controller 3110 , the controllable flow control valve 3190 controls and maintains the flow rate of desalted crude oil to the remaining refinery operations. Additionally, under control of the controller 3110 , the controllable flow control valve 3190 can also direct samples of the desalted crude to the measurement station 3200 . Measurements made on the solution samples would include but not be limited to impurity levels, temperature, residual hydroxyacid additive 3030 and wash water 3020 solution, etc. This information is sent to the controller 3110 .
[0080] In the embodiment of FIG. 3 , the controller 3110 takes measurements including but not limited to the various points described herein to evaluate the efficiency of the desalting mechanism 3000 . Based upon the type of crude oil being processed, the controller 3110 can adjust various factors of the desalting operation including but not limited to the following:
[0081] The crude oil supply 3010 feed rate through the controllable pump 3070 and controllable flow control valve 3120
[0082] The temperature of the crude oil supply 3010 through the controllable heater 3130 .
[0083] Control of the electrostatic desalter 3310 aqueous level and emulsion layers through the liquid level sensor 3340 , the controllable flow control valve 3330 , and the controllable flow control valve 3360 .
[0084] The electrostatic desalter 3310 electric field through the controllable power supply 3300 .
[0085] The solution mixture of hydroxyacid additive 3030 and wash water 3020 through the controllable fluid mixer 3040 .
[0086] The flow rate of the solution mixture of hydroxyacid additive 3030 and wash water 3020 through the controllable pump 3050 and controllable flow control valve 3060 .
[0087] The first emulsion formation of crude oil supply 3010 and recycled effluent from electrostatic desalter 3170 through controllable flow control valve 3220 , controllable pump 3370 , and controllable fluid mixer 3380 .
[0088] The second emulsion formation through controllable fluid mixer 3350 .
[0089] The electrostatic desalter 3170 electric field through the controllable electrical power supply 3150 .
[0090] Control of the electrostatic desalter 3170 water level and emulsion layers through the liquid level sensor 3210 , the controllable flow control valve 3220 , and the controllable flow control valve 3190 .
[0091] As different crude oils are processed by the desalting mechanism 3000 , the characteristics necessary to efficiently desalt the crude oil will require some adjustment. Additionally, differences in electrostatic desalter 3310 and 3170 characteristics, wash water supply 3020 purity, etc between different desalting mechanisms 3000 require the storage of different control settings. The memory/data storage 3100 function of the desalting mechanism 3000 allows the controller to access and update, if required, the control settings required to efficiently process various types of crude oil supplies 3010 . Preferably, the control settings are determined based upon maximizing the economic benefit for the desalting the crude oil supply 3010 .
[0092] FIG. 4 shows a process diagram 4000 of one embodiment of the method of the present invention for a typical crude oil electrostatic desalting operation. The desalting process is set to an initial state in step 4100 based upon the characteristics of the configuration of the desalting operation and the characteristics of the crude oil to be desalted. A hydroxyacid additive is mixed with wash water in step 4200 . The resulting hydroxyacid additive/wash water solution is then mixed with the crude oil to be desalted to create an emulsion in step 4300 . The emulsion is resolved into a hydrocarbon or oil phase and an aqueous or water phase in step 4400 . The characteristics of the effluent waste water, the desalted crude oil, or other points in the desalting operation that may or may not be dependent upon desalting configuration are measured in step 4500 . Characteristics of the desalting operation to include but not limited to one or more of the following may be varied in step 4600 to maximize the economic benefit of the desalting operation based upon the measurements in step 4500 : the crude oil feed rate, the crude oil temperature, the electric field characteristics of the dehydration/desalter mechanisms, the wash water flow rate, the crude oil emulsion formation, control of the dehydration/desalter water levels and emulsion layers, the hydroxyacid additive type and addition rate, and the effluent recycle (as appropriate).
[0093] The above embodiments are merely preferred and the scope of the invention defined by the claims below. | A method for removing metals, amines, and other impurities from crude oil in a desalting process that includes the steps of adding a wash water to the crude oil; adding the wash water to the crude oil to create an emulsion; adding to the wash water or the emulsion at least one water-soluble hydroxyacid; selecting the hydroxyacid additive from the group consisting of glycolic acid, gluconic acid, C.sub.2-C.sub.4 alpha-hydroxy acids, malic acid, lactic acid, poly-hydroxy carboxylic acids, thioglycolic acid, chloroacetic acid, polymeric forms of the above hydroxyacids, poly-glycolic esters, glycolate ethers, and ammonium salt and alkali metal salts of these hydroxyacids, and mixtures thereof; resolving the emulsion containing the crude oil, wash water, and hydroxyacid additive into a hydrocarbon phase and an aqueous phase using electrostatic coalescence, the undesired impurities being transferred to the aqueous phase; measuring the characteristics of one or more of the resulting crude oil output, effluent waste, and/or other intermediate points; and altering one or more characteristics of the desalting operation as a function of the measurements. Various oil desalting configurations are also provided. | 2 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention is in the field of balloon dilatation catheters used for cardiac angioplasty. More particularly, the present invention is in the field of balloon dilatation catheters of the so-called mono-rail configuration.
2. Related Technology
Therapeutic balloon dilatation catheters are known in the art which are of the so-called "mono-rail" configuration. Such monorail catheters generally have only a comparatively short distal mono-rail portion of the catheter which is slidably received over a guide wire. Other than the comparatively short distal portion of the guide wire which is received within the catheter, the remainder of the guide wire is exposed externally of the catheter. During angioplasty, a guide catheter is generally inserted into a patient and serves both to guide a therapeutic catheter along the vascular pathway to a location close to the heart, and to protect the patient's vessels from trauma which could be caused by contact from the therapeutic catheter.
However, this guide catheter provides a pathway only part of the way to the patient's heart. Beyond the distal end of the guide catheter, the therapeutic catheter generally extends unprotected within the vascular system of the patient. A guide wire is used to guide the therapeutic catheter the remainder of the distance to the location of treatment. With a mono-rail configuration of catheter, because the guide wire is exposed externally of the therapeutic catheter with the exception of the comparatively short mono-rail distal portion, the therapeutic catheter may be pulled back while leaving the guide wire in place, and without the need to use an extension for the guide wire. Because the guide catheter and guide wire both are left in place within the patient when the therapeutic catheter is withdrawn, a second therapeutic catheter of different size or type, for example, can easily retrace the path back to the location of treatment.
Unfortunately, the mono-rail type of catheters generally expose a section of the guide wire proximally of the distal mono-rail portion of the catheter and distally of the distal end of the guide catheter. The remainder of the guide wire is exposed. That is, only a portion of the guide wire is sheathed and slidably received in the distal end mono-rail portion of the therapeutic catheter, and the therapeutic catheter may be advanced beyond the end of the guide catheter sufficiently that a length of the guide wire is exposed. This exposed portion of guide wire can cause undesirable and detrimental local trauma to the patient's vascular system.
A conventional single-lumen mono-rail type of therapeutic catheter is known in accord with U.S. Pat. No. 4,762,129, issued 9 Aug. 1988, to T. Bonzel. The teaching of the Bonzel patent appears to be to configure a mono-rail catheter of the disclosed type with a comparatively short guide lumen which traverses the dilatation balloon of the catheter. The guide lumen is defined by a short section of flexible tubing. This section of tubing which traverses the dilatation balloon to provide a passage for the guide wire is about equal in length to the dilatation balloon itself. Proximally of the distal guide lumen of this catheter, the guide wire is exposed externally of the therapeutic catheter.
Another conventional therapeutic catheter of the mono-rail type is known in accord with U.S. Pat. No. 5,061,273, issued 29 Oct. 1991, to P. Yock. According to the teaching of the Yock patent, a mono-rail type of therapeutic catheter may by made with a comparatively long or extended distal mono-rail portion. However, the ease of catheter exchange which is the underlying principle for the mono-rail configuration of catheter is compromised by the extended length of the mono-rail portion of the catheter.
Yet another conventional mono-rail type of therapeutic catheter is seen in U.S. Pat. No. 4,748,982, issued 7 Jun. 1988 to M. J. Horzewski, et al. The teaching of the Horzewski patent appears to be to make a mono-rail type of catheter with a distal end mono-rail section which in the use position of the guide wire is sufficiently long so as to protect the patient from guide wire trauma. In order to still allow exchange of the therapeutic catheter while leaving the guide wire in place without the need for a guide wire extension, the Horzewski patent teaches to provide the distal end mono-rail section with a slit extending distally from a notch out of which the proximal portion of the guide wire extends from this mono-rail section. This slit extends distally almost to the dilatation balloon. When the guide wire is moved distally along this slit to a withdrawal position, the length of the mono-rail distal section of the therapeutic catheter is effectively shortened.
That is, with the catheter taught by the Horzewski patent, in order to facilitate withdrawal of the therapeutic catheter, this therapeutic catheter is withdrawn through the guide catheter until the notch is exposed externally of the patient. Thereafter, the guide wire must be forced to pass distally along the slit to a location adjacent to the dilatation balloon as the therapeutic catheter is further withdrawn, and without withdrawing the guide wire. In order to complete removal of the therapeutic catheter, the distal portion of this catheter must then be slid along the proximal part of the guide wire still without displacing the guide wire distal end from its preferred location within the patient across the treatment site. These two stages of catheter removal can be rather difficult because the guide wire is grasped frictionally in the slit of the catheter. Understandably, to accomplish this catheter removal without displacing the distal end of the guide wire is a process which requires considerable skill and care. In the event the guide wire distal end is inadvertently displaced from its desired position within the patient, then the route back to the treatment site is partially lost and must be reestablished by manipulation of the guide wire. Additional vascular trauma and risk to the patient can result from such manipulation of the guide wire to reestablish its desired position.
SUMMARY OF THE INVENTION
In view of the deficiencies of conventional technology, it is an object for the present invention to provide a mono-rail configuration of balloon dilatation therapeutic catheter which effectively includes a mono-rail portion of variable length, and which is free of a guide wire slit which can frictionally and undesirably grasp the guide wire during catheter withdrawal.
An additional object for the present invention is to provide such a therapeutic catheter with an axially movably mono-rail guide wire sheath which at a distal end portion thereof includes a sleeve portion in a first position sheathing the guide wire to effectively lengthen the mono-rail portion of the catheter.
Still another object of the present invention is to provide such a therapeutic catheter in which the guide wire sheath element may move axially in the distal direction to a second position overlying a part of the mono-rail guide portion of the therapeutic catheter proximal of the dilatation balloon, effectively shortening the mono-rail portion of the catheter.
Yet another object of the present invention is to provide a method of treatment in which a mono-rail configuration of catheter is used in a use configuration having an elongate mono-rail length to protect the patient from vascular trauma caused by contact of the guide wire with the vascular system, and is changed to a withdrawal configuration with a shortened mono-rail length for withdrawal of the catheter from the patient preparatory to catheter exchange.
Accordingly, the present invention provides an elongate balloon dilatation catheter having a distal mono-rail guide section, a dilatation balloon, and a mono-rail sheath member slidably movable axially along a shaft portion of the catheter between a first position sheathing the guide wire and effectively increasing the mono-rail length of the catheter, in a second position of the mono-rail sheath member the mono-rail length of the catheter substantially being defined only by the mono-rail guide section.
These and other objects and advantages of the present invention will be apparent from a reading of the following detailed description of a single exemplary preferred embodiment of the present invention, taken in conjunction with the following drawing Figures, in which like reference numerals designate the same feature, or features equivalent in structure or function.
DESCRIPTION OF THE DRAWING FIGURES
FIG. 1 schematically presents a representation of a guide catheter which is introduced into a patient's femoral artery and which extends at its distal end around the aortic arch to terminate at a location adjacent to the patient's heart. A therapeutic catheter extends through the guide catheter to the patient's heart.
FIG. 2 provides a plan view of a therapeutic catheter embodying the present invention in a use configuration, and in which the foreground portion of the Figure is drawn at a larger scale than the background portion in order to better illustrate salient features of the invention;
FIG. 3 provides a fragmentary view similar to the foreground portion of FIG. 2, and depicting the therapeutic catheter in transition between its use configuration and its withdrawal configuration; and
FIG. 4 is a fragmentary view similar to the foreground portion of FIG. 2, and depicting the therapeutic catheter in an alternative or withdrawal configuration.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Considering first FIGS. 1 and 2 together, a schematic representation is provided of a tubular guide catheter 10 introduced into a patient's femoral artery 12, and extending upwardly to terminate at the aortic arch 14. The guide catheter 10 includes a distal recurve section 16 which provides for a distal end 18 of the guide catheter 10 to dispose an end opening 20 of the tubular guide catheter 10 toward the patient's heart 22. A therapeutic balloon dilatation catheter 24 is introduced into the guide catheter 10 along with a guide wire assembly 26. From the opening 20 of the guide catheter 10, a distal end portion 28 of the therapeutic catheter 24 extends to the patient's heart 22. This distal end portion 28 is slidably received over a distal portion 30 of the guide wire assembly 26, which is seen projecting distally from an open end 32 of the therapeutic catheter 24. This guide wire assembly 26 at the distal portion 30 includes a radiopaque tip part 34 by which a physician can visualize the guide wire location and steer the guide wire assembly 26 and therapeutic catheter 24 to a treatment site for the patient.
Viewing now FIG. 2, the therapeutic balloon dilatation catheter 24 is shown in a use configuration. The catheter 24 includes an elongate catheter shaft portion 36 which is flexible, but which has good pushability and steerability because a proximal part 36a of the shaft is made of hypotube. That is, the shaft portion 36a is formed of small diameter metallic tubing having a wall thickness which is comparatively thin. As an example only, the tubing from which the shaft portion 36a is fabricated may have an outer diameter of about 0.023 inches, and a wall thickness of 0.0025 inches. Consequently, the shaft portion 36a has an internal passage or lumen 38 of about 0.018 inches diameter. This internal passage is best seen in the foreground portion of FIG. 1.
At a proximal end portion 40, the catheter 24 includes a coupling member 42, which is sealingly joined to the shaft portion 36a, and which defines a luer type of fitting 44. The luer fitting 44 communicates with the passage 38 of the shaft 36. Also, the proximal end portion 40 may also include one or more reinforcing sleeves 46, 48 extending distally from the coupling member 42.
At a location indicated by the arrow 50 along the length of the shaft 36, the metallic shaft portion 36a is joined in end-to-end relation with and forms a butt joint bond 52 with a flexible polymeric tubular part 36b of the shaft 36. The polymeric tubular part 36b is similar in diameter and wall thickness with the metallic part 36a, but is considerably more flexible. This polymeric tubular portion 36b of the shaft 36 defines the distal end portion for the catheter 24, as has been indicated with the numeral 28.
This catheter shaft portion 36b defines a distal end 56, which is spaced proximally of the distal end of the balloon catheter assembly 24, as will be further explained, and at which an expansible dilatation balloon 58 is secured to the shaft portion 36b by means of a bond 60. This dilatation balloon 58 includes a side wall 62 and a distal end part 64 which is similarly bonded to a comparatively smaller tubular member 66 at a bond 68. The tubular member 66 defines an internal passage 70 opening distally, and extends proximally in the balloon 58 and in the catheter shaft distal end portion 18 to a port 72. That is, the tubular member 66 is joined with the polymeric portion 36b of the catheter shaft 36 so that the passage 70 of this member opens outwardly on the portion 36b to define the port 72. It will be noted that the port 72 extends or is angulated toward the proximal end of the catheter 24. At its distal end 74, the tubular member 66 defines a corresponding distal end for the catheter 24.
In order to guide the catheter 24 along a vascular pathway, the passage 70 accepts and slidably passes the distal end portion 30 of the guide wire assembly 26. In other words, the passage 70 defines a mono-rail guide portion of the catheter 24 whereat the latter is slidably guided along the guide wire assembly 26. This guide wire assembly 26 includes an elongate shaft portion 80 which is generally wire-like. Distal end portion 30 of the guide wire assembly 26, in contrast, includes a spring-like portion 82 which is exceedingly flexible, but which may be preformed with a curve or bend for example, to help in steering the guide wire assembly 26 along a selected vascular pathway. The distal end portion 30 terminates in and carries the radiopaque tip member 34 to assist a physician in visualizing the location of the guide wire assembly 26 by use of a fluoroscope. It will be noted that proximally of the port 72, the guide wire assembly 26 is exposed externally of the catheter shaft 36.
In order to effectively extend the mono-rail portion of the catheter 24 beyond the length of the passage 70, a tubular mono-rail sheath member 86 is slidably carried on the outside of the shaft 36 between the sleeves 46, 48, and the balloon member 58. That is, the sheath member 86 includes a proximal end 88 which may abut one of the sleeves 46, 48 to define a limit of axial movement of the sheath member 86 in the proximal direction. Also, the sheath member 86 includes a distal end 90 which may abut the bond 60 to define a limit of axial movement of the sheath member 86 in the distal direction. More particularly, the sheath member 86 includes a proximal section 92, which has an inner diameter just sufficiently large enough so as to be slidably received over the shaft 36 of the catheter 24. At a bond 94, the proximal section 92 is joined with a distal section 96 having an inner diameter sufficiently larger that the outer diameter of the shaft 36 that the guide wire assembly 26 may also be received in this section of the sheath member 86. At the bond 94, the sheath member 86 defines a port 98 through which extends the guide wire assembly 26.
As is seen in FIG. 2, in a use configuration of the catheter 24 with the guide wire sheath member 86 withdrawn to its limit of axial movement in the proximal direction, the distal end 90 of the sheath member 86 is disposed just proximally of the port 72. Consequently, the guide wire assembly 26 is concealed within the monorail passage 70 of the catheter 24, and also within the section 96 of the sheath member. As so configured, the catheter 24 has a mono-rail length generally indicated with the numeral 100 and protects the patient from trauma caused by contact by the guide wire assembly 26. That is, the distal portions of the catheter 24 which may be exposed outside of the guide catheter 10 as seen in FIG. 1 have the guide wire assembly 26 sheathed or concealed within them. Consequently, the patient cannot be injured by the guide wire assembly 26.
In order to withdraw the catheter 24 (possibly to facilitate exchange of the catheter 24 with a different treatment catheter while leaving the guide wire assembly 26 in place for the replacement catheter to retrace the path back to the treatment site), the catheter 24 is first withdrawn in its use configuration of FIG. 2 until the distal end 74 is within the guide catheter 10. During this initial phase of withdrawal of the catheter 24, simple manual holding of a proximal end portion of the guide wire assembly 26 stationary will prevent the guide wire assembly from being dragged out of its established position across the treatment site. Next, as is depicted in FIG. 3 with arrow 108, the sheath member 86 is advanced distally to its withdrawal position seen in FIG. 4. This advancement of the sheath member 86 is accomplished by manually grasping of the proximal portions of the shaft 36a (at the coupling member 42, for example) and of the sheath member 86 (adjacent to the proximal end 88 thereof, for example), and moving the sheath member 86 distally relative to the shaft 36 while holding the latter stationary. While the balloon 58 is illustrate in an inflated condition in FIG. 4 for ease of illustration, it will be understood that the balloon 58 would ordinarily be deflated during all phases of withdrawal of the catheter 24. In this withdrawal configuration of the catheter 24, the sheath member 86 generally aligns port 72 with port 98. Consequently, the catheter 24 has a mono-rail length in its withdrawal configuration which is indicated by the numeral 102 in FIG. 4. It will be noted that the mono-rail length 100 of the catheter 24 in its use configuration is considerably greater, and may in fact be about twice the mono-rail length 102 in its withdrawal configuration of the catheter 24, as seen in FIG. 2.
In order to further assist a physician in visualizing the position of the balloon 58 within a patient, a radiopaque marker 104 may be carried on the tubular member 66 centered in the balloon 58. Also, a mark may be provided at 106 which appears proximally of the proximal end 88 of the sheath member 86 when the latter is advanced distally fully to its second position as seen in FIG. 4 to configure the catheter 24 for withdrawal.
While the present invention has been depicted, described, and is defined by reference to a particularly preferred embodiment of the invention, such reference does not imply a limitation on the invention, and no such limitation is to be inferred. The invention is capable of considerable modification, alteration, and equivalents in form and function, as will occur to those ordinarily skilled in the pertinent arts. The depicted and described preferred embodiment of the invention is exemplary only, and is not exhaustive of the scope of the invention. Consequently, the invention is intended to be limited only by the spirit and scope of the appended claims, giving full cognizance to equivalents in all respects. | A balloon dilatation catheter of the mono-rail type includes a distal mono-rail section traversing a dilatation balloon of the catheter, and a sheath member slidably movable axially of the remainder of the catheter and having a sheath section receiving an axial portion of the guide wire to in a first position effectively increase the mono-rail length of the catheter, and in a second position reduce the mono-rail length of the catheter to the length of the mono-rail section. | 0 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to Polish Patent Application No. PL382084 filed on Mar. 28, 2007, the contents of which are incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] This invention relates to amorphous carvedilol phosphate, and a method of manufacturing amorphous form of carvedilol phosphate.
[0004] 2. Description of the Related Art
[0005] (±)1-(9H-carbazol-4-yloxy)-3-[2-(2-methoxyphenoxy)ethylamino]propan-2-ol,
[0000]
[0000] known under its generic name as carvedilol, is a compound valued for its unique action mechanism combining non-selective inhibition of the β-adrenergic receptors in the heart, resulting in a decrease in blood pressure, heart rate and stroke volume, with the inhibition of the α1-adrenergic receptors, resulting in dilation of the blood vessels and decrease in the systemic vascular resistance.
[0006] The synthesis of an entire family of crystalline carbazolyl-4-oxy-propanolamine derivatives as well as their pharmaceutically acceptable salts, including carvedilol, was first disclosed in the European Pat. App. No. 0 004 920.
[0007] Although carvedilol and its derivatives are used in the treatment of hypertension and angina pectoris, their application is somewhat limited by their poor water solubility.
[0008] Poorly water-soluble substances show a better solubility when in dispergated form, resulting in a better bioavailability in comparison to their crystalline equivalents.
[0009] Amorphous forms can be obtained using several methods such, as solvent vaporization, solvent precipitation, lyophilization, spray-drying and spray congelation.
[0010] In general, however, amorphous forms are physically and chemically less stable from the crystalline forms, molecules of which are aligned thus demonstrating a lower inner energy.
[0011] In light of the foregoing, a novel form of carvedilol with greater aqueous solubility, chemical stability, etc. would offer many potential benefits for provision of medicinal products containing the drug carvedilol. Such benefits would include products with the ability to achieve desired or prolonged drug levels in a systemic system by sustaining absorption along the gastrointestinal tract of mammals (i.e., such as humans), particularly in regions of neutral pH, where a drug, such as carvedilol, has minimal solubility.
SUMMARY OF THE INVENTION
[0012] It was unexpectedly discovered that stable carvedilol phosphate in amorphous form can be obtained in a way that is economical and devoid of the shortcomings of previous literature methods.
[0013] In one embodiment, the invention provides amorphous carvedilol phosphate.
[0014] In certain classes of this embodiment, the X-ray powder diffraction spectrum of amorphous carvedilol phosphate lacks discemable acute peaks.
[0015] In certain classes of this embodiment, the X-ray powder diffraction spectrum of amorphous carvedilol phosphate obtained with a Cu K-alpha radiation contains only very broad characteristic peaks at about 6 (2θ) and 22.5 (2θ) in the range between 0 and 40 (2θ).
[0016] In certain classes of this embodiment, the infrared spectrum of amorphous carvedilol phosphate has sharp bands at about 3405, 3060, 2362, 1627, 1606, 1587, 1505, 1455, 1401, 1348, 1334, 1306, 1255, 1217, 1178, 1125, 1101, 1021, 945, 786, 474, 723, 512 cm −1 .
[0017] In certain classes of this embodiment, the X-ray powder diffraction spectrum of amorphous carvedilol phosphate obtained with a Cu K-alpha radiation is substantially as illustrated in FIG. 2
[0018] In certain classes of this embodiment, the infrared spectrum of amorphous carvedilol phosphate is substantially as illustrated in FIG. 1 .
[0019] In other aspects the invention provides a method of manufacturing amorphous carvedilol phosphate comprising removing solvent from carvedilol phosphate solution.
[0020] In certain classes of this embodiment, the solvent is removed by means of a spray dryer.
[0021] In certain classes of this embodiment, the solvent is removed by spray drying.
[0022] In certain classes of this embodiment, the solvent is methanol.
[0023] In another embodiment, the invention provides a method of manufacturing amorphous carvedilol phosphate comprising: (a) producing a mist of a carvedilol phosphate solution comprising carvedilol phosphate, a solvent, and a gas; and (b) vaporizing and removing the solvent by means of a drying gas.
[0024] In a class of this embodiment, the solvent is selected from methanol, ethanol, n-propanol, 2-propanol, their mixtures or their mixtures with water.
[0025] In a class of this embodiment, the gas is nitrogen, argon, or helium, and the drying gas is nitrogen, argon, or helium.
[0026] In a class of this embodiment, the mist of carvedilol phosphate solution in (a) has a temperature between 25 and 100° C.
[0027] In a class of this embodiment, vaporization of the solvent in (b) occurs at 120 to 175° C.
BRIEF DESCRIPTION OF THE DRAWINGS
[0028] The objects and advantages of the invention will become more readily apparent after reading the ensuing descriptions of the non-limiting illustrative embodiment and viewing the accompanying drawings, in which
[0029] FIG. 1 is an FT-IR spectrum of a typical lot of amorphous state carvedilol obtained by methods of the invention; and
[0030] FIG. 2 is an XRPD (x-ray powder diffraction) pattern thereof.
DETAILED DESCRIPTION OF THE INVENTION
[0031] Amorphous carvedilol phosphate is obtained through a very fast solvent vaporization of carvedilol phosphate solution, e.g., in a spray dryer apparatus comprising:
[0032] a container for the carvedilol phosphate solution,
[0033] a pump passing the solution to the atomiser,
[0034] a heater of the gas fed into the atomiser,
[0035] a heater of the drying gas fed into the drying chamber,
[0036] an atomiser producing a mist of the carvedilol phosphate solution by mixing the carvedilol phosphate solution and a gas,
[0037] a drying chamber where the process of the solvent vaporization takes place,
[0038] pipes feeding the product dust (amorphous carvedilol phosphate) to a separation unit for separating product from the drying gas,
[0039] a cyclone separator with a product receptacle where the separation of the gas and the product takes place,
[0040] a filter purifying the used drying gas of the product remains, and
[0041] a unit for regeneration of the drying gas (outdropping solvents or absorption).
[0042] Organic solvents, such as aliphatic monohydric alcohols: methanol, ethanol, n-propanol, 2-propanol, their mixtures and/or their mixtures with water are used to prepare the carvedilol phosphate solution.
[0043] Carvedilol phosphate solution is obtained by dissolving crystalline carvedilol phosphate in an organic solvent, mixture of organic solvents or their mixture with water, or by dissolving carvedilol in an organic solvent, mixture of organic solvents, or their mixture of one or more organic solvents with water and adding an equimolar amount of phosphoric acid (e.g., 70-85% aqueous solution of H 3 PO 4 ).
[0044] Concentrations of carvedilol phosphate solutions fed into the atomiser at room temperature range from 0.1 to 2.9% w/v. The temperatures of the heated solutions range from 25° C. to 100° C. and their concentrations range from 2.5-20% w/v.
[0045] The carvedilol phosphate solution is fed into the atomiser at a velocity ranging from 1 to 1,000 mL/min.
[0046] The gas fed into the atomiser and the drying gas is air or an inert gas such, as: nitrogen, argon, or helium.
[0047] The temperature of the gas fed into the atomiser ranges from 25 to 100° C.
[0048] The temperature of the drying gas fed into the drying chamber ranges from 120 to 175° C.
[0049] The drying gas is fed into the drying chamber concurrently with carvedilol phosphate aerosol.
[0050] The temperature of the waste gas (used drying gas) after exiting the cyclone ranges from 35 to 120° C.
[0051] The usage of the drying gas and the atomiser gas ranges from 10 to 200 Nm 3 /h.
[0052] The process of efficiency ranges from 80 to 98%.
[0053] The obtained product is examined using the X-ray diffraction method and infrared spectrometry. An exemplary spectrometric image is shown in FIG. 1 . The infrared spectrum shows sharp bands at about 3405, 3060, 2362, 1627, 1606, 1587, 1505, 1455, 1401, 1348, 1334, 1306, 1255, 1217, 1178, 1125, 1101, 1021, 945, 786, 474, 723, and 512 cm −1 . An exemplary image from the diffraction examination is shown in FIG. 1 . The X-ray powder diffraction spectrum obtained with a Cu K-alpha radiation lacks discemable acute peaks and contains only very broad characteristic peaks at about 6 (2θ) and 22.5 (2θ) in the range between 0 and 40 (2θ). Both spectrochemical analyses confirm that the examined product is amorphous.
EXAMPLES
[0054] The following spray dryers were used in the below-mentioned examples: (1) MOBILE MINOR™ Spray Dryer (GEA Niro Inc.) in closed-cycle; and (2) Anhydro MicraSpray 150 CC (Anhydro A/S).
Example 1
[0055] 1.0 kg of crystalline carvedilol phosphate was dissolved in 40 dm 3 of methanol at room temperature. The solution was fed into the atomiser through a peristaltic pump with the velocity of between 30 and 50 mL/min. The nitrogen fed into the atomiser was heated to the temperature of 63±2° C. The temperature of the nitrogen fed into the drying chamber was set to within the range of from 155 to 165° C. The product, amorphous carvedilol phosphate, was received at the exit of the cyclone separator in the amount of from 40 to 70 g/h. After 16-18 hours of work the prepared solution of carvedilol phosphate was used up and 950 g of amorphous product was obtained.
Example 2
[0056] 1.0 kg of crystalline carvedilol phosphate was dissolved in 10 dm 3 of methanol at the temperature of 50° C. The solution was fed into the atomiser through a peristaltic pump with the velocity of between 20 and 30 mL/min. The nitrogen fed into the atomiser was heated to the temperature of 63±2° C. The temperature of the nitrogen fed into the drying chamber was set to within the range of between 155 and 165° C. The product, amorphous carvedilol phosphate, was received at the exit of the cyclone separator in the amount of between 100 and 180 g/h. After 7-9 hours of work the prepared solution of carvedilol phosphate was used up and 920 g of amorphous product was obtained. | The subject of the invention is amorphous carvedilol phosphate and a method of manufacturing amorphous carvedilol phosphate comprising removing solvent from carvedilol phosphate solution by means of spray drying. | 2 |
TECHNICAL FIELD
[0001] The present invention relates to modified cellulases. More specifically, the invention relates to modified Family 6 cellulases with improved thermostability, alkalophilicity and/or thermophilicity. The present invention also relates to genetic constructs comprising nucleotide sequences encoding for modified Family 6 cellulases, methods for the production of the modified Family 6 cellulase from host strains and the use of the modified Family 6 cellulases in the hydrolysis of cellulose.
BACKGROUND OF THE INVENTION
[0002] The most abundant polysaccharide in the biosphere, cellulose, consists of D-glucose units linked together in linear chains via β-1,4 glycosidic bonds. These chains can vary in length and often consist of many thousands of units. Cellulose chains form numerous intra- and intermolecular hydrogen bonds, which result in the formation of insoluble cellulose microfibrils. This crystalline cellulose is a recalcitrant material with a natural half-life of over five million years.
[0003] In order to access this important renewable carbon source, microorganisms, such as bacteria and fungi, produce a cocktail of enzymes to break down crystalline cellulose into glucose. Three general classes of cellulase enzymes act synergistically to hydrolyze the crystalline cellulose into the simple energy source glucose. Endo-β-1,4-glucanases (EC 3.2.1.4) randomly hydrolyze amorphous regions of crystalline cellulose generating oligosaccharides of various lengths and consequently new chain ends. Cellobiohydrolases (or exo-β-1,4-cellobiohydrolase, EC 3.2.1.91) hydrolyze processively cellobiose units from one end of the cellulose chain. Finally, β-1,4-glucosidases (EC 3.2.1.21) hydrolyse cellobiose into glucose.
[0004] Most cellobiohydrolases and endo-β-1,4-glucanases are multidomain proteins consisting of a catalytic core domain and a cellulose-binding domain separated by a flexible linker region. The cellulose-binding domain promotes adsorption of the enzyme to regions of the cellulosic substrate (Tomme, P., et al. 1988 . Eur. J. Biochem 170:575-581; Lehtio J., et al. 2003 Proc. Natl. Acad. Sci. USA. 100:484-489), while the catalytic core domain is responsible for the cleavage of cellulose. The linker region may ensure an optimal interdomain distance between the core domain and the cellulose-binding domain (Srisodsuk M., et al. 1993 . J. Biol. Chem. 268:20756-20761).
[0005] The catalytic domains are classified into the glycoside hydrolase families based on amino acid sequence similarities whereby a family comprises enzymes having similar fold and hydrolytic mechanisms but may differ in their substrate specificity. Trichoderma reesei contains known cellulase genes for two cellobiohydrolases, i.e., Cel7A (also known as CBH1, which is a member of Family 7) and Cel6A (CBH2), at least eight endo-β-1,4-glucanases, i.e., Cel7B (EG1), Cel5A (EG2), Cel12A (EG3), Cel61A (EG4), Cel45A (EG5), Cel74A (EG6), Cel61B (EG7), and Cel5B (EG8), and at least seven β-1,4-glucosidase, i.e., Cel3A (BG1), CellA (BG2), Cel3B (BG3), Cel3C (BG4), CellB (BG5), Cel3D, and Cel3E (Foreman, P. K., et al. 2003 . J. Biol. Chem. 278:31988-31997).
[0006] T. reesei Cel6A (or TrCel6A) is one of the two major cellobiohydrolases secreted by this fungus and has been shown to be efficient in the enzymatic hydrolysis of crystalline cellulose. TrCel6A is a member of glycoside hydrolase Family 6, which comprises enzymes that hydrolyse β-1,4 glycosidic bonds with inversion of anomeric configuration and includes cellobiohydrolases as well as endo-β-1,4-glucanases. The three dimensional structures of TrCel6A (Rouvinen J., et al. 1990 . Science 249:380-386. Erratum in: Science 1990 249:1359), Thermobifida fusca endo-β-1,4-glucanase Cel6A (TfCel6A, Spezio M., et al. 1993 . Biochemistry. 32:9906-9916), Humicola insolens cellobiohydrolase Cel6A (HiCel6A, Varrot, A., et al. 1999 Biochem. J. 337:297-304), Humicola insolens endo-β-1,4-glucanase Cel6B (HiCel6B, Davies, G. J., et al. 2000 . Biochem. J. 348:201-207), and Mycobacterium tuberculosis H37Rv Cel6A (MtCel6A, Varrot. A., et al. 2005 . J. Biol. Chem. 280:20181-20184) are known.
[0007] Applications of cellulase enzymes in industrial processes are numerous and have proven commercially useful within the textile industry for denim finishing and cotton softening; in the household and industrial detergents for color brightening, softening, and soil removal; in the pulp and paper industries for smoothing fiber, enhancing drainage, and de-inking; in the food industry for extracting and clarifying juice from fruits and vegetables, and for mashing; in the animal feed industry to improve their nutritional quality; and also, in the conversion of plant fibers into glucose that are fermented and distilled to make low CO 2 cellulose ethanol to reduce fossil fuel consumption, which is an emerging industry around the world (e.g. Gray K. A., et al. 2006 . Curr. Opin. Chem. Biol. 10:141-146).
[0008] In order to obtain enzyme variants with improved stability properties, three strategies have generally been used within the art: 1) isolation of thermophilic enzymes from extremophiles, residing in severe environments such as extreme heat or cold, high salt concentrations or high or low pH conditions (e.g. U.S. Pat. No. 5,677,151 U.S. Pat. Appl. No. 20060053514); 2) protein engineering by rational design or site-directed mutagenesis, which relies on sequence homology and structural alignment within a family of proteins to identify potentially beneficial mutations using the principles of protein stability known in the art (reviewed in: Eijsink, V. G., et al. 2004 . J. Biotechnol. 113:105-20.); and 3) directed evolution involving the construction of a mutant library with selection or screening to identify improved variants and involves a process of iterative cycles of producing variants with the desired properties (recently reviewed in: Eijsink V G, et al. 2005 . Biomol. Eng. 22:21-30). This approach requires no structural or mechanistic information and can uncover unexpected beneficial mutations. Combining the above strategies has proven to be an efficient way to identify improved enzymes (Chica R. A., et al. 2005 . Curr. Opin. Biotechnol. 16:378-384).
[0009] Using rational design, Zhang et al. (Zhan S et al., 2000 . Eur. J. Biochem. 267:3101-15), introduced a new disulfide bond across the N- and C-terminal loops from TfCel6B using two double mutations, and four glycine residue mutations were chosen to improve thermostability. None of the mutations increased thermostability of this cellobiohydrolase and most mutations reduced thermostability by 5-10° C. Surprisingly, the double mutation N233C-D506C showed a decrease of 10C for the T 50 (Zhang S et al., 2000 . Eur. J. Biochem. 267:3101-15), or a slight increase of about 2° C. for the Tso (Ai, Y. C. and Wilson, D. B. 2002. Enzyme Microb. Technol. 30:804-808). Wohlfahrt (Wohlfahrt, G., et al. 2003 . Biochemistry. 42:10095-10103) disclosed an increase in the thermostability of TrCel6A, at an alkaline pH range, by replacing carboxyl-carboxylate pairs into amide-carboxylate pairs. A single mutant, E107Q, and a triple mutant, E107Q/D170N/D366N, have an improved T m above pH 7 but a lower T m at pH 5, which is the optimal pH of the wild-type TrCel6A. These mutations are found in, or close to, the N- and C-terminal loops. Hughes et al (Hughes, S. R., et al. 2006 . Proteome Sci. 4:10-23) disclose a directed evolution strategy to screen mutagenized clones of the Orpinomyces PC-2 cellulase F (OPC2Cel6F) with targeted variations in the last four codons for improved activity at lower pH, and identified two mutants having improved activity at lower pH and improved thermostability.
[0010] The above reports describing rational design of Family 6 cellulases suggest that the introduction of hydrogen or disulfide bonds into the C-terminal loops is not a good strategy to increase the thermostability at optimal hydrolysis conditions. Furthermore, stabilizing the exo-loop of the T. reesei Family 7 cellobiohydrolase Cel7A, which forms the roof of the active site tunnel, by introducing a disulfide bond with mutation D241C/D249C showed no improvement in thermostability (von Ossowski I., et al. 2003 . J. Mol. Biol. 333:817-829).
[0011] TrCel6A variants with improved thermostability are described in US Patent Publication No. 20060205042. Mutations were identified based alignment of TrCel6A amino acid sequence with those of eight Family 6 members using structural information and a modeling program. This alignment served as basis for the determination of a so-called consensus sequence. Those mutations that, according to the 3D-structure model of TrCel6A, fit into the structure without disturbance and were likely to improve the thermostability of the enzyme were selected as replacement for improved thermostability of TrCel6A. Among those identified as improving the thermostability of TrCel6A was the mutation of the serine at position 413 to a tyrosin (S413Y). This mutation increased the retention of enzymatic activity after a 1 hour pre-incubation at 61° C. from 20-23% for the parental TrCel6A to 39-43% for TrCel6A-S413Y; however, after a 1 hour pre-incubation at 65° C., the parent TrCel6A retained 5-9% of its activity while TrCel6A-S413Y retained 6-8% of its activity. The melting temperature, or Tm, improved by 0.2-0.3° C., from 66.5° C. for the parental TrCel6A to 66.7-66.8° C. for TrCel6A-S413Y.
[0012] Despite knowledge of the mechanisms of and desirable attributes for cellulases in the above and related industrial applications, the development of thermostable cellulases with improved stability, catalytic properties, or both improved stability and catalytic properties, would be advantageous. Although thermophilic and thermostable enzymes may be found in nature, the difficulty in achieving cost-effective large-scale production of these enzymes has limited their penetration into markets for industrial use. Therefore, a need exists for improved stable cellulases which can be economically produced at a high-level of expression by industrial micro-organisms such as T. reesei.
SUMMARY OF THE INVENTION
[0013] The present invention relates to modified Family 6 cellulases. More specifically, the invention relates to modified Family 6 cellulases that exhibit enhanced thermostability, alkalophilicity and/or thermophilicity. The present invention also relates to genetic constructs comprising nucleotide sequences encoding for modified Family 6 cellulases, methods for the production of the modified Family 6 cellulase from host strains and the use of the modified Family 6 cellulases in the hydrolysis of cellulose.
[0014] It is an object of the invention to provide an improved cellulase with increased thermostability, thermophilicity and alklophilicity.
[0015] This invention relates to a modified Family 6 cellulase produced by substitution of an amino acid at position 413 with a proline. The position(s) of the amino acid substitution(s) are determined from sequence alignment of the modified cellulase with a Trichoderma reesei Cel6A amino acid sequence as defined in SEQ ID NO: 1. The modified Family 6 cellulase exhibits enhanced thermostability, alkalophilicity, thermophilicity, or a combination thereof, relative to a parent Family 6 cellulase from which the Family 6 cellulase is derived.
[0016] The modified Family 6 cellulase may be derived from a filamentous fungus, such as Trichoderma reesei . In one embodiment of the invention, the modified cellulase is not derived from a cellulase which has a naturally-occurring proline residue at position 413 (TrCel6A numbering), for example a native Family 6 cellulase (CelF from Orpinomyces sp PC-2) which contains a proline residue at position 413.
[0017] This invention also includes a modified Family 6 cellulase comprising a proline residue at position 413 and further comprising polar amino acids at positions selected from 231, 305, 410 or a combination thereof.
[0018] The present invention also pertains to the modified Family 6 cellulase comprising a proline at position 413 and further comprising a substituted amino acid at position 231 selected from the group consisting of Ser, or Thr. The substituted amino acid at position 231 may be Ser.
[0019] The present invention also pertains to the modified Family 6 cellulase comprising a proline at position 413 and further comprising a substituted amino acid at position 305 selected from the group consisting of Ser and Thr.
[0020] The present invention also pertains to the modified Family 6 cellulase comprising a proline residue at position 413 and further comprising a substituted amino acid at position 410 selected from the group consisting of Gln and Asn.
[0021] The present invention also includes a Family 6 cellulase comprising a proline residue at position 413 and further comprising substituted amino acids at positions 231 and 305 with Ser residues (i.e. 231S, 305S), and substitution of an amino acid at position 410 with Gln. The modified Family 6 cellulase comprising these mutations may be from a filamentous fungus, such as Trichoderma reesei.
[0022] The present invention also relates to a modified Family 6 cellulase comprising a proline residue a position 413 and having an increase in thermostability relative to a parent cellulase, as measured by the “T 50 ”, from about 5° C. to about 30° C. higher, or from about 9° C. to about 20° C. higher than the corresponding parent cellulase.
[0023] The present invention also relates to a modified Family 6 cellulase comprising a proline residue at position 413 and having an increase in its temperature for maximal activity (T opt ) of from about 1.5° C. to about 30° C. higher, or from about or 2.5° C. to about 20° C. higher, that the T opt of a parent Family 6 celulase. The present invention also relates to a modified Family 6 cellulase comprising a proline residue at position 413 and having an increase in its pH for maximal activity (pH opt ) of about 0.5 units to about 6.0 units higher, relative to a parent cellulase.
[0024] The present invention also relates to a modified Family 6 cellulase selected from the group consisting of:
(SEQ ID NO: 12) TrCe16A-S413P; (SEQ ID NO: 13) TrCe16A-G82E-G231S-N305S-R410Q-S413P; (SEQ ID NO: 14) TrCe16A-G231S-S413P; (SEQ ID NO: 15) TrCe16A-N305S-S413P; (SEQ ID NO: 16) TrCe16A-R410Q-S413P; (SEQ ID NO: 17) TrCe16A-G231S-N305S-S413P; (SEQ ID NO: 18) TrCe16A-G231S-R410Q-S413P; (SEQ ID NO: 19) TrCe16A-N305S-R410Q-S413P; (SEQ ID NO: 20) TrCe16A-G231S-N305S-R410Q-S413P; (SEQ ID NO: 21) HiCe16A-Y420P; and (SEQ ID NO: 22) PcCe16A-S407P.
[0025] The invention also relates to genetic constructs for directing expression and secretion of the modified Family 6 cellulase from a host microbe including, but not limited to, strains of Trichoderma reesei.
[0026] The present invention relates to a genetic construct comprising a DNA sequence encoding a modified Family 6 cellulase comprising a proline residue at position 413, which DNA sequence is operably linked to DNA sequences regulating its expression and secretion from a host microbe. Preferably, the DNA sequences regulating the expression and secretion of the modified Family 6 cellulase are derived from the host microbe used for expression of the modified cellulase. The host microbe may be a yeast, such as Saccharomyces cerevisiae , or a filamentous fungus, such as Trichoderma reesei.
[0027] The invention also relates to a genetic construct comprising a DNA sequence encoding a modified Family 6 cellulase comprising a proline residue at position 413 and further comprising substituted amino acids at positions 231 and 305 with Ser and substitution of an amino acid at position 410 with Gln. The DNA sequence is operably linked to DNA sequences regulating its expression and secretion from a host microbe. Preferably, the DNA sequences regulating the expression and secretion of the modified Family 6 cellulase are derived from a filamentous fungus, including, but not limited to, Trichoderma reesei.
[0028] The invention also relates to a genetically modified microbe capable of expression and secretion of a modified Family 6 cellulase comprising a proline residue at position 413 and comprising a genetic construct encoding the modified Family 6 cellulase. In one embodiment, the modified Family 6 cellulase further comprises Ser residues at positions 231 and 305 and a Gln residue at position 410. Preferably, the genetically modified microbe is a yeast or filamentous fungus. The genetically modified microbe may be a species of Saccharomyces, Pichia, Hansenula, Trichoderma, Aspergillus, Fusarium, Humicola, Neurospora or Phanerochaete.
[0029] The present invention also relates to the use of a modified Family 6 cellulase comprising a proline residue at position 413 for treatment of a cellulosic substrate.
[0030] The invention also relates to the process of producing the modified Family 6 cellulase, including transformation of a yeast or fungal host, selection of recombinant yeast or fungal strains expressing the modified Family 6 cellulase, and culturing the selected recombinant strains in submerged liquid fermentations under conditions that induce the expression of the modified Family 6 cellulase.
[0031] Family 6 cellulases of the present invention comprising a proline residue at position 413 display improved thermostability and thermophilicity or alkalophilicity relative to wild-type Family 6 cellulases. Without wishing to be bound by theory, improved thermostability of the modified Family 6 cellulase results from amino acid substitutions that stabilize the C-terminal loop of Family 6 cellobiohydrolases by increasing the stability of the small α-helix.
[0032] Such cellulases find use in a variety of applications in industry that require enzyme stability and activities at temperatures and/or pH values above that of the native enzyme. For example, modified Family 6 cellulases, as described herein, may be used for the purposes of saccharification of lignocellulosic feedstocks for the production of fermentable sugars and fuel alcohol, improving the digestibility of feeds in ruminant and non-ruminant animals, pulp and paper processing, releasing dye from and softening denim.
[0033] This summary of the invention does not necessarily describe all features of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0034] These and other features of the invention will become more apparent from the following description in which reference is made to the appended drawings wherein:
[0035] FIG. 1 shows an amino acid sequence alignment among Family 6 cellulases. The amino acid numbering for each cellulase is compared with that of the Trichoderma reesei Cel6A (TrCel6A; SEQ ID NO: 1) as indicated at the left and right of each sequences. The residues at positions 213, 305, 410 and 413 (relative to TrCel6A) are indicated with an asterisk. The residues identical with the corresponding amino acid in TrCel6A are in bold. For cellulases with a cellulose-binding domain, only the catalytic core sequences are presented. CfCel6B (SEQ ID NO:2); HiCel6A (SEQ ID NO:4); HiCel6B (SEQ ID NO:11); MtCel6A (SEQ ID NO:9); NpCel6A (SEQ ID NO:5); OpC2Cel6F (SEQ ID NO:6); PE2Cel6A (SEQ ID NO:8); TfCel6A (SEQ ID NO: 10); TfCel6B (SEQ ID NO:3).
[0036] FIG. 2 depicts plasmid vectors a) YEp352/PGK91-1ΔNheI-xyl SS -cbh2 vector, b) YEpFLAGΔKpn10-cbh2 directing the expression and secretion of native and modified TrCel6A from recombinant Saccharomyces cerevisiae (The same organization if found for the TrCel6 variants cloned in the same vectors), c) YEpFLAGΔKpn10-PcCel6A directing the expression and secretion of native and modified PcCel6A from recombinant Saccharomyces cerevisiae (The same organization if found for the PcCel6 variants cloned in the same vectors), d) YEpFLAGΔKpn10-HiCel6A directing the expression and secretion of native and modified HiCel6A from recombinant Saccharomyces cerevisiae (The same organization if found for the HiCel6 variants cloned in the same vectors).
[0037] FIG. 3 depicts the vector pC/X—S413P-TV used to transform and direct the expression and secretion of modified TrCel6A from recombinant Trichoderma reesei . As shown, the TrCel6A-S413P gene is operable linked to the promoter of the cbh1 (TrCel7A) gene, the secretion signal peptide of the xln2 (TrXyl11B) genes and the transcriptional terminator of the native cbh2 (TrCel6A) gene. The selection marker is the Neurospora crassa pyr4 gene.
[0038] FIG. 4 shows the effect of pre-incubation temperature on the relative residual activity (%), as measured by the release of reducing sugars from α-glucan in a 30 minutes assay at a) 65° C., of the native TrCel6A and modified Family 6 cellulases TrCel6A-S413P, TrCel6A-R410Q-S413P, TrCel6A-G231 S-N305S-S413P, TrCel6A-G231S-R410Q-S413P, TrCel6A-N305S-R410Q-S413P and TrCel6A-G231S-N305S-R410Q-S413P, b) 60° C., of the native PcCel6A and modified Family 6 cellulases PcCel6A-S407P, c) 65° C., of the native HiCel6A and modified Family 6 cellulases HiCel6A-Y420P, after 15 minutes incubation at temperatures between 45° C. and 75° C.
[0039] FIG. 5 shows the effect of increasing pre-incubation times on the relative residual activity (%), as measured by the release of reducing sugars a soluble β-glucan substrate in a 30 minutes assay at a) 65° C., of the native TrCel6A and modified Family 6 cellulases TrCel6A-S413P, TrCel6A-R410Q-S413P, TrCel6A-G231S-N305S-S413P, TrCel6A-G231S-R410Q-S413P, TrCel6A-N305S-R410Q-S413P and TrCel6A-G2311S-N305S-R410Q-S413P after 0-120 minutes incubation at 60° C. and b) 60° C., of the native PcCel6A and modified Family 6 cellulases PcCel6A-S407P after 0-120 minutes incubation at 55° C.
[0040] FIG. 6 shows the effect of temperature on the enzymatic activity of a) the native TrCel6A and modified Family 6 cellulases TrCel6A-S413P, TrCel6A-G82E-G231S-N305S-R410Q-S413P, TrCel6A-R410Q-S413P, TrCel6A-G231S-N305S-S413P, TrCel6A-G231S-R410Q-S413P, TrCel6A-N305S-R410Q-S413P and TrCel6A-G231S-N305S-R410Q-S413P b) the native PcCel6A and modified Family 6 cellulases PcCel6A-S407P and c) the native HiCel6A and modified Family 6 cellulases HiCel6A-Y420P during 30 minutes incubation at pH 5.0. The data are normalized to the activity observed at the temperature optimum for each enzyme.
[0041] FIG. 7 shows the effect of pH on the enzymatic activity of a) the native TrCel6A and modified Family 6 cellulases TrCel6A-S413P, TrCel6A-G82E-G231S-N305S-R410Q-S413P, TrCel6A-R410Q-S413P, TrCel6A-G231S-N305S-S413P, TrCel6A-G231S-R410Q-S413P, TrCel6A-N305S-R410Q-S413P and TrCel6A-G231S-N305S-R410Q-S413P b) the native PcCel6A and modified Family 6 cellulases PcCel6A-S407P and c) the native HiCel6A and modified Family 6 cellulases HiCel6A-Y420P during 30 minutes incubation at pH 3.95-7.45. The data are normalized to the activity observed at the pH optimum for each enzyme.
[0042] FIG. 8 shows the relative activity of whole Trichoderma cellulases comprising TrCel6A or TrCel6A-S413P (along with all of the remaining native Trichoderma reesei cellulase components) in the enzymatic hydrolysis of pretreated lignocellulosic substrate after 0, 4, 20.5, 28, 40.5, 52, 68, 76 and 96 hours of pre-incubation in the absence of substrate at 50° C. in 50 mM citrate buffer, pH 5.0.
DESCRIPTION OF PREFERRED EMBODIMENT
[0043] The present invention relates to modified cellulase. More specifically, the invention relates to modified Family 6 cellulases with enhanced thermostability, alkalophilicity and/or thermophilicity. The present invention also relates to genetic constructs comprising nucleotide sequences encoding for modified Family 6 cellulases, methods for the production of the modified Family 6 cellulase from host strains and the use of the modified Family 6 cellulases in the hydrolysis of cellulose.
[0044] The following description is of a preferred embodiment by way of example only and without limitation to the combination of features necessary for carrying the invention into effect.
[0000] Modified Family 6 Cellulases
[0045] Family 6 (previously, Family B) cellulases enzymes are a group of enzymes that hydrolyse the β-1,4 glucosidic linkages in cellulose with inversion of configuration of the anomeric carbon (Claeyssens, M. and Henrissat, B. 1992, Protein Science 1: 1293-1297). Family 6 cellulases share extensive amino acid sequence similarity ( FIG. 1 ). A cellulase is classified as a Family 6 cellulase if it comprises amino acids common to other Family 6 cellulase, including two aspartic acid (D) residues which may serve as catalytic residues. These aspartic acid residues are found at positions 175 and 221 (see FIG. 1 ; based on TrCel6A ( Trichoderma reesei Cel6A enzyme) amino acid numbering). Most of the Family 6 cellulases identified thus far are mesophilic. However, this family also includes thermostable cellulases from Thermobifida fusca (TfCel6A and TfCel6B) and the alkalophilic cellulases from Humicola insolens (HiCel6A and HiCel6B).
[0046] The topology of Family 6 catalytic domains is a variant of the α/β-barrel with a central β-barrel containing seven parallel β-strands connected by five α-helices. One important difference between Family 6 cellobiohydrolases and endo-β-1,4-glucanases is the length of their N- and C-terminal loops present on each side of the active site and which are responsible for their functional behavior on cellulose. In the cellobiohydrolases, an extensive C-terminal loop forms a tunnel with the N-terminal loop enclosing the active site. This confers the unique property of cellobiohydrolases to attack the ends of crystalline cellulose where the N- and C-terminal loops maintain a single cellulose chain in the active site and facilitate the processive degradation of the substrate. In the endo-β-1,4-glucanases, the C-terminal loop is reduced in length and the N-terminal loop pulls it away from the active site and could be also shorter resulting in a more open active site allowing access to internal β-1,4 glycosidic bonds of cellulose for hydrolysis. The role of these loops in the functional behavior of Family 6 enzymes on cellulose was confirmed by the deletion of fifteen amino acids of the C-terminal loop of the Cellulomonas fimi cellobiohydrolase Cel6B in order to mimic the properties of an endo-β-1,4-glucanase (Meinke A., et al. 1995 . J. Biol. Chem. 270:4383-4386). The mutation enhanced the endo-β-1,4-glucanase activity of the enzyme on soluble cellulose, such as carboxymethylcellulose, and altered its cellobiohydrolase activity on insoluble cellulose.
[0047] Non-limiting examples of Family 6 cellulases that may be modified following the general approach and methodology as outlined herein are described in Table 1 below.
TABLE 1 Family 6 cellulase enzymes Microbe Cellulase SEQ ID No. Cellulomonia fimi CfCe16B 2 Humicola insolens HiCe16A 4 Humicola insolens HiCe16B 11 Mycobacteriumn tuberculosis MtCe16A 9 Neocallimatrix patriciarum NpCe16A 5 Orpinomyces sp. PC-2 OpC2Ce16F 6 Phanerochaete chrysosporium PcCe16A 7 Pyromyces sp. E2 PE2Ce16A 8 Thermobifida fusca TfCe16A 10 Thermobifida fusca TfCe16B 3
[0048] Examples of preferred Family 6 cellulases, which are not meant to be limiting, include Trichoderma reesei Cel6A, Humicola insolens Cel6A, Phanerochaete chrysosporium Cel6A, Cellulomonas fimi Cel6B, Thermobifida fusca Cel6B. More preferably, the modified cellulase of the present invention comprises a modified Trichoderma reesei Cel6A enzyme.
[0049] By “modified Family 6 cellulase” or “modified cellulase”, it is meant a Family 6 cellulase in which the amino acid at position 413 (said position determined from sequence alignment of said modified cellulase with a Trichoderma reesei Cel6A amino acid sequence as defined in SEQ ID NO:1) has been altered, using techniques that are known to one of skill in the art, to a proline and which exhibits improvements in thermostability, thermophilicity, alkalophilicity, or a combination thereof, over the corresponding unmodified Family 6 cellulase. Techniques for altering amino acid sequences include, but are not limited to, site-directed mutagenesis, cassette mutagenesis, random mutagenesis, synthetic oligonucleotide construction, cloning and other genetic engineering techniques (Eijsink V G, et al. 2005 . Biomol. Eng. 22:21-30, which is incorporated here in by reference). It will be understood that the modified cellulase may be derived from any Family 6 cellulase. The modified cellulase may be derived from a wild-type cellulase or from a cellulase that already contains other amino acid substitutions.
[0050] For the purposes of the present invention, the parent cellulase is a cellulase that does not contain a substitution of its original amino acid at position 413 (said position determined from sequence alignment of said modified cellulase with a Trichoderma reesei Cel6A amino acid sequence as defined in SEQ ID NO: 1) by a proline and is otherwise identical to the modified cellulase. As such, the parent cellulase may be a cellulase that contains amino acid substitutions at other positions that have been introduced by genetic engineering or other techniques. However, a parent cellulase does not include those cellulases in which the naturally occurring amino acid at position 413 is a proline.
[0051] By “TrCel6A numbering”, it is meant the numbering corresponding to the position of amino acids based on the amino acid sequence of TrCel6A (Table 1; FIG. 1 ; SEQ ID NO:1). As disclosed below, and as is evident by FIG. 1 , Family 6 cellulases exhibit a substantial degree of sequence similarity. Therefore, by aligning the amino acids to optimize the sequence similarity between cellulase enzymes, and by using the amino acid numbering of TrCel6A as the basis for numbering, the positions of amino acids within other cellulase enzymes can be determined relative to TrCel6A.
[0052] Enzyme thermostability can be defined by its melting temperature (T m ), the half-life (t 1/2 ) at defined temperature, and the temperature at which 50% of the initial enzyme activity is lost after incubation at defined time (T 50 ). Thermophilic enzymes typically show common structural elements that have been identified as contributing factors to enzyme thermostability when compared to their mesophilic counterparts (e.g. see Sadeghi M., et al. 2006 . Biophys. Chem. 119:256-270). These structural elements include greater hydrophobicity, better packing, increased polar surface area, deletion or shortening of loops, interactions, smaller and less numerous cavities, stability of α-helix, increase in aromatic interactions, additional disulfide bridges or metal binding and glycosylation sites, decreased glycines and enhanced prolines content, increased hydrogen bonding and salt bridges, improved electrostatic interactions, decreased of thermolabile residues, and conformational strain release.
[0053] For the purposes of the present invention, a cellulase exhibits improved thermostability with respect to a corresponding parent cellulase if it has a T 50 which is at least about 4° C., or at least about 9° C. higher than that of the parent cellulase, or for example a cellulase having a T 50 from about 4° C. to about 30° C. higher, or any amount therebetween, or a T 50 from about 9° C. to about 30° C. higher, or any amount therebetween, when compared to that of the parent cellulase. The T 50 is the temperature at which the modified or the natural enzyme retains 50% of its residual activity after a pre-incubation for 15 minutes and is determined by the assay detailed in Example 10.4. As set forth in Example 10.4, the residual activity against β-glucan in a 30 minute assay at 65° C. is normalized to 100%.
[0054] The modified Family 6 cellulase may have Tso which is about 4° C. to about 30° C. higher than that of a corresponding parent cellulase, or any range therebetween, about 5° C. to about 20° C. higher, or any range therebetween, about 8° C. to about 15° C. higher, or any range therebetween, or from about 9° C. to about 15° C. higher, or any range therebetween. For example, the modified cellulase may have a T 50 that is at least about 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, or 30° C. higher than that of the corresponding parent cellulase.
[0055] The modified Family 6 cellulase may also be characterized as having a T 50 above 65° C. (or at least 5° C. above that of the corresponding parent Family 6 cellulase), for example, the modified cellulase may have a T 50 from about 65° C. to about 90° C., or any amount therebetween. The modified Family 6 cellulase may have a T 50 above 70° C. (or at least 9° C. above the parent Family 6 cellulase) for example, the modified cellulase may have a Tso from about 70° C. to about 90° C., or any amount therebetween. The Family 6 cellulase may have a T 50 of 50, 55, 60, 65, 70, 75, 80, 85 or 90° C. or any amount therebetween.
[0056] For the purposes of this specification, a cellulase exhibits improved thermophilicity with respect to a corresponding parent cellulase if the cellulase exhibits a temperature optimum (T opt ) that is at least about 1.5° C. higher than the T opt of the corresponding parent cellulase. For example, a cellulase exhibits improved thermophilicity if the cellulase exhibits a temperature optimum (T opt ) that is from about 1.5° C. to about 30° C. or any amount therebetween, higher than the T opt of the corresponding parent cellulase By temperature optimum or T opt , it is meant the highest temperature at which a cellulase exhibits its maximal activity. For the purposes of this specification, the T opt of a Family 6 cellulase is determined by measuring the temperature profile of activity against a β-glucan substrate as detailed in Example 10.1. The temperature profile for the activity of the cellulase is measured at its pH optimum.
[0057] The modified Family 6 cellulase may have a T opt which is at least about 1.5° C. to about 30° C. higher than the T opt of a corresponding parent Family 6 cellulase. In a preferred embodiment, the T opt of the modified Family 6 cellulase is at least about 2.5° C. to about 20° C. higher than the T opt of parent Family 6 cellulase. For example, the modified Family 6 cellulase may have a T opt of at least about 1.5, 2.5, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0, 15.0, 20.0, 25.0, or 30° C. higher than that of the corresponding parent cellulase.
[0058] The terms “thermostability” and “thermophilicity” have been used interchangeably within the literature. However, the use of the terms as defined herein is consistent with the usage of the terms in the art (Mathrani, I and Ahring, B. K. 1992 Appl. Microbiol. Biotechnol. 38:23-27).
[0059] For the purposes of the present invention, a cellulase exhibits improved alkalophilicity with respect to a corresponding parent cellulase if the cellulase exhibits a pH opt that is at least about 0.5 units higher than the pH opt of the parent cellulase. By pH opt , it is meant the highest pH at which a cellulase exhibits its maximal activity. For the purpose of this specification, the pH opt is determined by measuring the pH profile of a Family 6 cellulase as set out in Example 10.2.
[0060] The modified Family 6 cellulase may have a pH opt that is at least about 0.5 units to about 6.0 units, or any amount therebetween, higher than the pH opt of the parent Family 6 cellulase. In a preferred embodiment, the pH opt , of the modified Family 6 cellulase is at least about 0.8 units to about 5.0 units, or any amount therebetween, higher than the pH opt parent Family 6 cellulase. For example, the pH opt of the cellulase may be about 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5 or 6.0 units higher than the pH opt of the parent cellulase.
[0061] As described in more detail herein, several mutant Family 6 cellulases have been prepared that exhibit enhanced thermostability, thermophilicity, alkalophilicity, or a combination thereof. A list of several mutants, which is not to be considered limiting in any manner, is presented in Table 2.
TABLE 2 Modified Family 6 cellulases New mutant TrCe16A SEQ ID NO: TrCe16A-S413P 12 TrCe16A-G82E-G231S-N305S-R410Q-S413P 13 TrCe16A-G231S-S413P 14 TrCe16A-N305S-S413P 15 TrCe16A-R410Q-S413P 16 TrCe16A-G231S-N305S-S413P 17 TrCe16A-G231S-R410Q-S413P 18 TrCe16A-N305S-R410Q-S413P 19 TrCe16A-G231S-N305S-R410Q-S413P 20 HiCe16A-Y420P 21 PcCe16A-S407P 22
Genetic Constructs Comprising Modified Family 6 cellulases
[0062] The present invention also relates to genetic constructs comprising a DNA sequence encoding the modified Family 6 cellulase operably linked to regulatory DNA sequences directing the expression and secretion of the modified Family 6 cellulase from a host microbe. The regulatory sequences are preferably functional in a fungal host. The regulatory sequences may be derived from genes that are highly expressed and secreted in the host microbe under industrial fermentation conditions. In a preferred embodiment, the regulatory sequences are derived from any one or more of the Trichoderma reesei cellulase or hemicellulase genes.
[0063] The genetic construct may further comprise a selectable marker to enable isolation of a genetically modified microbe transformed with the construct as is commonly known with the art. The selectable marker may confer resistance to an antibiotic or the ability to grow on medium lacking a specific nutrient to the host organism that otherwise could not grow under these conditions. The present invention is not limited by the choice of selection marker, and one of skill may readily determine an appropriate marker. In a preferred embodiment, the selection marker confers resistance to hygromycin, phleomycin, kanamycin, geneticin, or G418, complements a deficiency of the host microbe in one of the trp, arg, leu, pyr4, pyr2, ura3, ura5, his, or ade genes or confers the ability to grow on acetamide as a sole nitrogen source. In a more preferred embodiment, the selectable marker is the Neurospora crassa pyr4 gene encoding orotidine-5′-decarboxylase.
[0000] Genetically Modified Microbes Comprising Modified Family 6 cellulases
[0064] The modified Family 6 cellulase may be expressed and secreted from a genetically modified microbe produced by transformation of a host microbe with a genetic construct encoding the modified Family 6 cellulase. The host microbe is preferably a yeast or a filamentous fungi, including, but not limited to, a species of Saccharomyces, Pichia, Hansenula, Trichoderma, Hypocrea, Aspergillus, Fusarium, Humicola, Neurospora or Phanerochaete . Typically, the host microbe is one from which the gene(s) encoding any or all Family 6 cellulases have been deleted. In a most preferred embodiment, the host microbe is an industrial strain of Trichoderma reesei.
[0065] The genetic construct may be introduced into the host microbe by any number of methods known by one skilled in the art of microbial transformation, including but not limited to, treatment of cells with CaCl 2 , electroporation, biolistic bombardment, PEG-mediated fusion of protoplasts (e.g. White et al., WO 2005/093072, which is incorporated herein by reference).
[0066] After selecting the recombinant fungal strains expressing the modified Family 6 cellulase, the selected recombinant strains may be cultured in submerged liquid fermentations under conditions that induce the expression of the modified Family 6 cellulase.
[0000] Hydrolysis of Cellulosic Substrates
[0067] The present invention also relates to the use of the modified Family 6 cellulases described herein for the hydrolysis of a cellulosic substrate. By the term “cellulosic substrate”, it is meant any substrate derived from plant biomass and comprising cellulose, including, but not limited to, lignocellulosic feedstocks for the production of ethanol or other high value products, animal feeds, forestry waste products, such as pulp and wood chips, and textiles.
[0068] By the term “lignocellulosic feedstock”, it is meant any type of plant biomass such as, but not limited to, non-woody plant biomass, cultivated crops such as, but not limited to, grasses, for example, but not limited to, C4 grasses, such as switch grass, cord grass, rye grass, miscanthus, reed canary grass, or a combination thereof, sugar processing residues, for example, but not limited to, baggase, beet pulp, or a combination thereof, agricultural residues, for example, but not limited to, soybean stover, corn stover, rice straw, rice hulls, barley straw, corn cobs, wheat straw, canola straw, oat straw, oat hulls, corn fiber, or a combination thereof, forestry biomass for example, but not limited to, recycled wood pulp fiber, sawdust, hardwood, for example aspen wood, softwood, or a combination thereof.
[0069] In the saccharification of lignocellulosic feedstocks for the production of ethanol, or other products, cellulases of the invention may be used to hydrolyze a pretreated feedstock produced by, for example, but not limited to, steam explosion (see Foody, U.S. Pat. No. 4,461,648, which is incorporated herein by reference and to which the reader is directed for reference). Pretreatment may involve treatment of the feedstock with steam, acid, or typically a combination of steam and acid, such that the cellulose surface area is greatly increased as the fibrous feedstock is converted to a muddy texture, with little conversion of the cellulose to glucose. The cellulase enzymes of the invention then may be used to hydrolyze cellulose to glucose in a subsequent step. The glucose may then be converted to ethanol or other products.
[0070] Modified cellulase enzymes of the invention may be added to pulp or wood chips to enhance the bleaching or reduce refining energy of the pulp. The pulp may be produced by a chemical pulping process or by mechanical refining.
[0000] Increasing the Thermostability of Family 6 Cellulases
[0071] The thermostability of the mutant Family 6 cellulase was compared via pre-incubation of the enzyme in the absence of substrate at different temperatures. After 15 minutes, the residual activity of the cellulase was determined via a standard assay with soluble β-glucan as a substrate.
[0072] The effect of the S413P mutation, alone or in combination with one or more of G231S, N305S and R410Q, on the thermostability of Family 6 cellulase was determined via a comparative study of the modified TrCel6A-S413P and the parent TrCel6A. After pre-incubation at higher temperatures for up to 120 minutes, the former retained greater residual activity than the latter ( FIG. 5 a ).
[0073] The pre-incubation temperature that allowed Family 6 cellulase to retain 50% of the residual activity, T 50 , was determined. For the modified Family 6 cellulase, TrCel6A-S413P, the T 50 was 64.1° C., as compared to 59° C. for the parent TrCel6A ( FIG. 4 a ). This represented an increase in the thermostability by over 5° C. through the introduction of the S413P mutation.
[0074] The T 50 of the other TrCel6A variants was at least 3.2° C. higher then wild-type TrCel6A. PcCel6A-S407P and Hicel6A-Y420P also have shown an increase in T 50 when compared to their respective parent enzyme ( FIGS. 4 b and c ).
[0000] Increasing the Thermophilicity of Family 6 Cellulases
[0075] The thermophilicity of the modified Family 6 cellulases was determined by measuring effect of the assay temperature on the hydrolysis of β-glucan.
[0076] All modified Family 6 cellulases shown an improved T opt for β-glucan hydrolysis when compared to their respective wild-type except variant TrCel6A-G231S-N305S-R410Q-S413P which on the other hand exhibits a broad temperature range with more then 80% of the maximum activity ( FIG. 6 ). Among all TrCel6A variants, TrCel6A-S413P has the higher optimal temperature at 72.2° C., an increase of 5.6° C. in thermophilicity compared to wild-type TrCel6A ( FIG. 6 a ). PcCel6A-S407P and HiCel6A-Y420P also exhibit an increase in optimal temperature when compared to their respective wild-type ( FIGS. 6 b and c ).
[0000] Increasing the Alkalophilicity of Family 6 Cellulases
[0077] The effect of the S413P mutation, alone or in combination with one or more of G231S, N305S and R410Q, on the pH/activity profile of Family 6 cellulase was also studied.
[0078] All modified Family 6 cellulases exhibit increased alkalophilicity when compared to their wild-type. For TrCel6A, the most important shift was observed with variants TrCel6A-G231S-R410Q-S413P (+1.25 pH units) followed by TrCel6A-G231S-N305S-R410Q-S413P (+1.01 pH units).
[0079] Cellulase systems comprising modified Family 6 cellulases in combination with non-Family 6 cellulases show improved thermostability. A Trichoderma cellulase system comprising TrCel6A-S413P maintains at least 80% of its maximal activity after incubation in the absence of substrate at 50° C. for 96 hours, while the corresponding cellulase system comprising the parent TrCel6A maintains only 50% of its maximal activity ( FIG. 8 ).
[0080] In summary, improved thermostable, alkalophilic and/or thermophlic mutant Family 6 cellulase of the invention comprise a proline residue at position 413 and may further comprise one or more than one of the following amino acid substitutions:
(i) a substituted amino acid at position 231 such as a polar amino acid, including, but not limited to, Ser; (ii) a substituted amino acid at position 305, such as a polar amino acid, including, but not limited to, Ser; (iii) a substituted amino acid at position 410, such as a polar amino acid, including, but not limited to, Gln; and (iv) combinations of any of the above mutations set out in (i) to (iii).
[0085] Non-limiting examples of preferred Family 6 cellulase mutants comprising a S413P in combination with the amino acid substitutions listed above are given in Table 2.
[0086] Furthermore, the modified Family 6 cellulase of the present invention may comprise amino acid substitutions not listed above in combination with S413P.
[0087] The above description is not intended to limit the claimed invention in any manner. Furthermore, the discussed combination of features might not be absolutely necessary for the inventive solution.
EXAMPLES
[0088] The present invention will be further illustrated in the following examples. However, it is to be understood that these examples are for illustrative purposes only and should not be used to limit the scope of the present invention in any manner.
Examples
[0089] Example 1 describes the strains and vectors used in the following examples. Examples 2-5 describe the random mutagenesis of the TrCel6A gene, cloning of the random mutagenesis libraries in yeast vectors and high-throughput screening to identify modified Family 6 cellulases with increased thermostability. Examples 6-8 describe the cloning, recombination and expression of the modified and native Family 6 cellulase genes in an alternative yeast vector for higher expression. Example 9 describes the enzymatic characterization of modified Family 6 cellulases. Example 10 describes genetic constructs to express and secrete the modified Family 6 cellulases in a filamentous fungus. Example 11 describes the transformation of fungal protoplasts with genetic constructs expressing modified Family 6 cellulases. Example 12 describes the production of modified Family 6 cellulases from modified microbes in submerged liquid cultures. Example 13 describes the characterization of whole Trichoderma cellulases comprising modified Family 6 cellulases in combination with cellulases from other Families.
Example 1
Strains and Vectors
[0090] Saccharomyces cerevisiae strain DBY747 (his3-Δ1 leu2-3 leu2-112 ura3-52 trp1-289 (amber mutation) gal(s) CUP(r)) was obtained from the ATCC. S. cerevisiae strain BJ3505 (pep4::HIS3 prb-Δ10.6R HIS3 lys2-208 trp1-Δ101 ura3-52 gal2 can1) was obtained from Sigma and was a part of the Amino-Terminal Yeast FLAG Expression Kit.
[0091] A strain of Trichoderma reesei obtained derived from RutC30 (ATCC #56765; Montenecourt, B. and Eveleigh D. 1979 . Adv. Chem. Ser. 181: 289-301) comprising a disrupted native TrCel6A gene was used in the experiments described herein.
[0092] Escherichia coli strains HB101 (F − thi-1 hsdS20 (r B − , m B − ) supE44 recA13 ara-14 leuB6 proA2 lacY1 galK2 rpsL20 (str I ) xyl-5 mtl-1) and DH5α (F − φ80lacZΔM15 Δ(lacZYA-argF)U169 recA1 endA1 hsdR17 (r k − , m k + ) phoA supE44 thi-1 gyrA96 relA1 λ − ) were obtained from Invitrogen.
[0093] Humicola insolens and Phanerochaete chrysosporium strains were obtained from ATCC® (#22082™ and #201542™ respectively).
[0094] The YEp352/PGK91-1 vector was obtained from the National Institute of Health. The YEpFLAG-1 vector was obtained from Sigma as a part of the Amino-Terminal Yeast FLAG Expression Kit. The pALTER®-1 vector was obtained from Promega as a part of the Altered Site® II in vitro mutagenesis System. The pBluescript® II KS-vector was obtained from Stratagene.
Example 2
Cloning of the TrCel6A gene into the YEp352/PGK91-1 and Transformation in Yeast
[0000] 2.1 Isolation of total RNA from T. reesei and Generation of Total cDNA.
[0095] T. reesei biomass was grown under inducing conditions as described in example 13 then 50 mg of biomass was used to isolate total RNA with the Absolutely RNA® Miniprep Kit (Stratagene) according to the manufacturer procedure. Total cDNA was generated from the total RNA using the SuperScript™II Reverse Transcriptase (Invitrogen) according to the manufacturer procedure.
[0000] 2.2 Cloning and Transformation in Yeast.
[0096] In order to facilitate cloning using NheI and KpnI restriction enzymes, the unique NheI site at position 1936 of the YEp352/PGK91-1 vector was blunted using the DNA Polymerase I large (Klenow) fragment to generate YEp352/PGK91-1ΔNheI.
[0097] The cbh2 gene encoding TrCel6A was amplified by PCR from total cDNA (generated as described in example 2.1) using primers (C2STU 5 and C2STU3 that introduce StuI-NheI sites upstream and a KpnI-BglII-StuI sites downstream to the coding sequence. In parallel, the secretion signal peptide of the TrXyl11B gene was amplified by PCR from a genomic clone of TrXyl11B (pXYN2K2, example 11.3) using primers to introduce BglII at the 5′ end and an NheI site at 3′ end of the amplicon, which was subsequently cloned using these restriction sites into pBluescript® II KS-(Stratagene) to generate the plasmid pXYNSS-Nhe. The amplicon was then cloned into the unique NheI and Bgl II sites of pXYNSS-Nhe. A fragment comprising the TrCel6A gene operably linked to the secretion signal peptide of TrXyl11B with BglII sites at the 5′ and 3′ ends was subsequently amplified by PCR from this intermediate construction using primers (BGL2XYF and C2STU3). This amplicon was cloned in the BglII site of the YEp352/PGK91-1ΔNheI vector to yield to the YEp352/PGK91-1ΔNheI-xyl SS -cbh2 vector ( FIG. 2 a ) and transformed in yeast strain DBY747 using the procedure described by Gietz, R. D. and Woods, R. A. (Gietz, R. D. and Woods, R. A. 2002 . Meth. Enzym. 350: 87-96) and plated on SC-Ura plate. Primer sequences are listed below:
StuI NheI C2STU5: 5′GAT AGG CCT GCT AGC TGC TCA AGC GTC TGG GGC (SEQ ID NO: 24) StuI BglII KpnI C2STU3: 5′ATC AGG CCT AGA TCT GGT ACC TTA CAG GAA CGA TGG (SEQ ID NO: 25) BglII BGL2XYF: 5′GAT C AG ATC T AT GGT CTC CTT CAC CTC CCT C (SEQ ID NO: 26)
Example 3
[0098]
Component
g/L
Yeast Nitrogen Base without amino
1.7
acid and ammonium sulfalte (BD)
(NH 4 ) 2 SO 4 (Sigma)
5.0
Complete Supplement Media without uridine (Clontech)
0.77
Agar (BD)
17.0
Glucose (Fisher)
20.0
pH 5.6
Making Error Prone-PCR Libraries of cbh2
[0099] Random mutagenesis libraries were generated using two methods: a Mn 2+ /dITP method and a biased nucleotides method. For the Mn 2+ /dITP method, the TrCel6A gene was amplified from YEp352/PGK91-1ΔNheI-xyl SS -cbh2 vector using the above-mentioned C2STU3 and BGL2XYF primers in a two step PCR method. In the first step, the amplification occurs for 20 cycles in the presence 20 μM MnCl 2 . The second step is done with the same primers but using the product from the first step as template and with 0, 25, 50, 75 or 100 μM dITP (0 μM being a control). For the biased nucleotides method, the PCR is conducted with 1:3, 1:5 or 1:10 molar ratio between purine bases and pyrimidine bases respectively.
[0100] To get mostly mutations in the core of the enzyme, the final amplicon in both cases was cloned using the XhoI and KpnI restriction sites in the YEp352/PGK91-1ΔNheI-xyl SS -cbh2 vector (XhoI cuts right after sequence coding for S55's codon in the linker of the enzyme) and transformed in S. cerevisiae strain DBY747.
Example 4
Making Site-Directed Semi-Random Libraries of TrCel6A
[0101] Glycine residues have no β-carbon and thus have considerably greater backbone conformational freedom. By analyzing the three-dimensional structure of TrCel6A, 4 glycines residues were targeted to decrease this degree of freedom, namely G90, G85, G231 and G384. All but G231 positions were saturated and G231 was randomly mutated for an alanine, a proline, a serine or a threonine by megaprimer PCR using the following primers:
G 90 to Xxx: (SEQ ID NO:27) 5′ CCA ACA AAA GGG TTN NNT GAA TAC GTA GCG G G 85 to Xxx: (SEQ ID NO:28) 5′ CCC AAG GAG TGA CNN NAA CAA AAG GGT TG G 231 to A/P/S/T: (SEQ ID NO:29) 5′ GGT GAC CAA CCT CNC NAC TCC AAA GTG TG G 384 to Xxx: (SEQ ID NO:30) 5′ CCG CAA ACA CTN NNG ACT CGT TGC TG
[0102] All amplicons were cloned in the YEp352/PGK91-1ΔNheI-xyl SS -cbh2 vector as described in example 3.
Example 5
Screening of TrCel6A Gene Libraries for Modified Family 6 Cellulases with Increased Thermostability
[0103] A total of 3371 TrCel6A variants generated as per Example 3 and 4 were screened as follows: each yeast colony was cultured in a well of a 96-deep well plate containing 1 mL of YPD (1% yeast extract, 2% peptone, 2% glucose) media and one 1.5 mm glass bead for 2 days in a Vortemp apparatus (Labnet) at 650 rpm and at 30° C. The plate was centrifuged at 3,000×g for 5 minutes then 300 μL of supernatant was filtered through each of two Biodyne B positively charged nylon membranes (Pall Gelman) using a Bio-Dot apparatus (Bio-Rad).
[0104] Membranes were placed on a moist (not wet) Whatman paper containing 50 mM sodium citrate at pH 4.8. One was incubated for 12 minutes at 62° C. and the other one at room temperature (control). Membranes were then placed on agar plates containing β-glucan substrate and incubated overnight at 50° C. in a humidity chamber:
Component g/L (NH 4 ) 2 SO 4 (Sigma) 5.0 β-glucan (Barley, Medium Viscosity; Megazyme) 2.0 Agar (BD) 17.0 Glucose (Fisher) 20.0 pH 5.6
[0105] Agar plates were then stained 30-60 minutes by covering them with a 0.1% (w/v) Congo Red solution then rinsed 2-3 times with demineralized water to remove unbound dye and covered with 1M NaCl for 10-15 min. The clearing zones could be observed and compared between the control and the plate that was covered with the heat treated membrane. Each plate was scrutinized by at least two people and every positive variant that appeared to maintain its activity after the 12 min incubation at 62° C. when compared to the wild-type TrCel6A control was considered as potential positive. Each potential positive clone was produced again in microculture to allow observation of the phenotype on an additional occasion and to reduce the possibility of false negative.
[0106] From that screening, five positive clones were sequenced to identify the mutations they carry. Clone E6 contained a S413P mutation, clones G3 and F7 both contained a G231S mutation, clone A3 contained a N305S mutation and clone 7 contained a R410Q mutation as well as a G82E mutation at the end of the linker peptide.
Example 6
Cloning Modified TrCel6A Genes into the YEpFLAG-1 Vector for Higher Expression from Saccharomyces cerevisiae
[0107] In order to facilitate cloning of the modified TrCel6A genes identified in Example 5 into the YEpPLAG-1 vector in such a way as to operabling link the genes to the a mating factor secretion signal peptide, two modifications were necessary. First, the unique KpnI site present in the α secretion signal peptide sequence (bp 1457) of the YEpFLAG-1 vector was removed. This was done by PCR using two complementary mutagenic primers (5′-FLAGΔKpnI and 3′-FLAGΔKpnI). The mutagenesis reaction was then digested with DpnI for 1 hour at 37° C. and the plasmid was allowed to recircularize by placing the tube in boiling water and allowed to cool slowly to room temperature. This reaction was transformed directly in E. coli DH5α chemically competent cells. A clone that was digested only once with KpnI was sequenced to confirm the desired mutation and was used for further work and named YEpFLAGΔKpn. Primer sequences are listed below:
ΔKpnI 5′-FLAGΔKpnI: 5′CTA AAG AAG AAG G GG TAC A TT TGG ATA AAA GAG AC (SEQ ID NO:31) 66 KpnI 3′-FLAGΔKpnI: 5′GTC TCT TTT ATC CAA A TG TAC C CC TTC TTC TTT AG (SEQ ID NO:32)
[0108] Second, the T. reesei cbh1 gene was amplified from pCOR132 (Example 11.2) by PCR using primers to introduce XhoI-NheI sites at the 5′ end and Kpn1-Apa1 sites at 3′ end of the amplified fragment. This fragment was then inserted as an XhoI/ApaI fragments into the XhoI/ApaI linearized YEpFLAG-1 expression vector. The resulting vector, YEpFLAGΔKpn10, allows insertion of the modified TrCel6A genes identified in Example 5 as NheI/KpnI fragments in such a way that the coding regions are operably linked to the α secretion signal peptide.
[0109] The YEp352/PGK91-1ΔNheI-xyl SS -cbh2 vectors containing native or modified TrCel6A genes were isolated from transformants of yeast strain DBY747 using method modified from Hoffman and Winston (Hoffman, C. S., and Winston, F. 1987 . Gene 57: 267-272) and transformed in E. coli HB101 chemically competent cells. The modified TrCel6A genes were removed from the YEp352/PGK91-1ΔNheI-xyl SS -cbh2 vectors by digestion with NheI and KpnI and cloned in the YEpFLAGΔKpn10 using the same restriction enzymes. The final constructs, YEpFLAGΔKpn10-cbh2, YEpFLAGΔKpn10-G82E-R410Q, YEpFLAGΔKpn10-N305S YEpFLAGΔKpn10-S413P and YEpFLAGΔKpn10-G231S ( FIG. 2 b ), were transformed into yeast strain BJ3505 using the procedure described by Gietz and Woods (Gietz R. D. and Woods R. A. 2002 . Meth. Enzym. 350: 87-96) and plated on SC-trp plate. The integrity of the cloned region of all variants was confirmed by DNA sequence analysis. The amino acid sequence of the parent TrCel6A produced by this yeast vector (SEQ ID NO. 23) shows the C-terminal extension containing the FLAG peptide. However, it was determined experimentally that this small peptide extension does not in any way contribute to the thermostability, thermophilicity or alkalophilicity of the parent or modified TrCel6A cellulases.
[0110] SC-trp Pate Contains:
Component g/L Yeast Nitrogen Base without amino acid and ammonium 1.7 sulfalte (BD) (NH 4 ) 2 SO 4 (Sigma) 5.0 Yeast Synthetic Drop-Out Media Supplement without 1 Tryptophan (Sigma) Agar (BD) 20 Glucose (Fisher) 20
Example 7
Generation of Other TrCel6A Variants, PcCel6A, PcCel6A-S407P, HiCel6A and HiCel6A-Y420P and Their Cloning in the YEpFLAG-1 Vector
[0000] 7.1 Generation of Other TrCel6A Variants.
[0111] TrCel6A variant R410Q-S413P was obtained by error-prone PCR on the TrCel6A-S413P variant while cloned in the YEp352/PGK91-1ΔNheI using the Mutazyme® II DNA polymerase (Stratagene). It was then amplified from that source using primers 5′FLAG-Cel6A-GR and 3′FLAG-Cel6A-GR that introduce sequences homologue to the YEpFLAG-1 vector upstream the NheI site and downstream the ApaI site respectively.
[0112] Mutagenic primers in conjunction with primer 3′FLAG-Cel6A-GR were used to generate megaprimer PCR of the following TrCel6A mutation combinations: G231S-S413P, N305S-S413P, G231S-N305S-S413P, G231S-R410Q-S413P, N305S-R410Q-S413P and G231S-N305S-R410Q-S413P. The resulting PCR products were isolated and used as a reverse primer in conjunction with the forward primer 5′FLAG-Cel6A-GR to generate final constructs. Primers sequences are listed below:
5′G231SCBH2 (SEQ ID NO: 35) 5′GGT GAC CAA CCT CTC TAC TCC AAA GTG TG 5′N305SGBH2 (SEQ ID NO: 36) 5′CAA TGT CGC CAG CTA CAA CGG G 5′Ce16A-E82G (SEQ ID NO: 38) 5′GTA CCT CCA GTC GGA TCG GGA ACC GCT 5′FLAG-Ce16A-GR (SEQ ID NO:39) 5′AGA GAC TAC AAG GAT GAC GAT GAC AAG GAA TTC CTC GAG GCT AGC TGC TCA AGC G 3′FLAG-Ce16A-GR (SEQ ID NO: 40) 5′GAC CCA TCA GCG GCC GCT TAC CGC GGG TCG ACG GGC CCG GTA CCT TAC AGG AAC G
7.2 Generation PcCel6A and PcCel6A-S407P.
[0113] Lyophilized P. chrysosporium was resuspended in 300 μL sterile H 2 O and 50 μL were spreaded onto PDA plates. Plates were incubated at 24° C. for 4 days. Spores for P. chrysosporium were inoculated on a cellophane circle on top of a PDA plate and biomass was harvested after 4-6 days at 24° C. Then, 50 mg of biomass was used to isolate total RNA with the Absolutely RNA® Miniprep Kit (Stratagene) according to the manufacturer procedure. Total cDNA was generated from the total RNA using the SuperScript™II Reverse Transcriptase (Invitrogen) according to the manufacturer procedure. Gene encoding for PcCel6A was amplified from the cDNA using the following primers:
5′PcCe16A-cDNA (SEQ ID NO: 41) 5′CTA TTG CTA GCT CGG AGT GGG GAC AGT GCG GTG GC 3′PcCe16A-cDNA (SEQ ID NO: 42) 5′CTA TTG AAT TCG GTA CCC TAC AGC GGC GGG TTG GCA GCA GAA AC
[0114] PCR amplicon was clone in the pGEM®-T Easy vector by TA-cloning following manufacturer's recommendations. The gene encoding for PcCel6A was then amplified from that source using primers 5′FLAG-PcCel6A-GR and 3′FLAG-PcCel6A-GR that introduce sequences homologue to the YEpFLAG-1 vector upstream the NheI site and downstream the SstII site respectively.
[0115] Mutagenic primer 5′PcCel6A-S407P in conjunction with primer 3′FLAG-PcCel6A-GR was used to generate megaprimer PCR. The resulting PCR product was isolated and used as a reverse primer in conjunction with the forward primer 5′FLAG-PcCel6A-GR to generate final construct. Primers sequences are listed below:
5′FLAG-PcCe16A-GR (SEQ ID NO: 43) 5′AAGGATGACGATGACAAGGAATTCCTCGAGGCTAGCTCGGAGTG GGG ACAGTGC 3′FLAG-PcCe16A-GR (SEQ ID NO: 44) 5′TGGGACGCTCGACGGATCAGCGGCCGCTTACCGCGGCTACAGCG GCG GGTTGGC 5′PcCe16A-S407P (SEQ ID NO: 45) 5′CCCCGCTACGACCCTACTTGTTCTCTG
7.3 Generation HiCel6A and HiCel6A-Y420P.
[0116] Lyophilized H. insolens was resuspended in 300 μL sterile H 2 O and 50 μL was spreaded onto Emerson YPSS pH 7 agar plate (0.4% Yeast extract, 0.1% K 2 HPO 4 , 0.05% MgSO 4 .7H 2 O, 1.5% Glucose, 1.5% Agar). Fungus was incubated for 6 days at 45° C. then spores were inoculated in Novo media (as per Barbesgaard U.S. Pat. No. 4,435,307): Incubation for 48 hours at 37° C. in 100 mL growth phase media (2.4% CSL, 2.4% Glucose, 0.5% Soy oil, pH adjusted to 5.5, 0.5% CaCO 3 ), then 6 mL of pre-culture was transferred into 100 mL production phase media (0.25% NH 4 NO 3 , 0.56% KH 2 PO 4 , 0.44% K 2 HPO 4 , 0.075% MgSO 4 .7H 2 O, 2% Sigmacell, pH adjusted to 7, 0.25% CaCO 3 ) and culture was incubated for up to 4 days prior to biomass harvest. Then, 50 mg of biomass was used to isolate total RNA with the Absolutely RNA® Miniprep Kit (Stratagene) according to the manufacturer procedure. Total cDNA was generated from the total RNA using the SuperScript™II Reverse Transcriptase (Invitrogen) according to the manufacturer procedure. Gene encoding for HiCel6A was amplified from the cDNA using the following primers:
5′HiCe16A-cDNA (SEQ ID NO: 46) 5′CTA TTG CTA GCT GTG CCC CGA CTT GGG GCC AGT GC 3′HiCe16A-cDNA (SEQ ID NO: 47) 5′CTA TTG AAT TCG GTA CCT CAG AAC GGC GGA TTG GCA TTA CGA AG
[0117] PCR Amplicon was Clone in the pGEMO-T Easy vector by TA-Cloning following manufacturer's recommendations. The gene encoding for HiCel6A was then amplified from that source using primers 5′FLAG-HiCel6A-GR and 3′FLAG-HiCel6A-GR that introduce sequences homologue to the YEpFLAG-1 vector upstream the NheI site and downstream the ApaI site respectively.
[0118] Mutagenic primer 5′HiCel6A-Y420P in conjunction with primer 3′FLAG-HiCel6A-GR was used to generate megaprimer PCR. The resulting PCR product was isolated and used as a reverse primer in conjunction with the forward primer 5′FLAG-HiCel6A-GR to generate final construct. Primers sequences are listed below:
5′FLAG-HiCe16A-GR (SEQ ID NO: 48) 5′AAGGATGACGATGACAAGGAATTCCTCGAGGCTAGCTGTGCCCC GACTTGGGGC 3′FLAG-HiCe16A-GR (SEQ ID NO: 49) 5′AGCGGCCGCTTACCGCGGGTCGACGGGCCCGGTACCTCAGAACGG CGGATTGGC 5′HiCe16A-Y420P (SEQ ID NO: 50) 5′GCCCGCTACGACCCTCACTGCGGTCTC
7.4 Cloning of the Other TrCel6A Variants, PcCel6A, PcCel6A-S407P, HiCel6A and HiCel6A-Y420P in YEpFLAG-1 and Transformation in BJ3505.
[0119] The YEpFLAGΔKpn10 vector (example 6) was digested with NheI and ApaI and the empty vector fragment was isolated. This linear fragment and the final PCR products generated in example 8.1 and 8.3 were cloned and transformed simultaneously by in vivo recombination (Butler, T. and Alcalde, M. 2003. In Methods in Molecular Biology, vol. 231: (F. H. Arnold and G. Georgiou, editors), Humana Press Inc. Totowa (New Jersey), pages 17-22).
[0120] The YEpFLAGΔKpn10 vector (example 6) was digested with NheI and SstII and the empty vector fragment was isolated. This linear fragment and the final PCR products generated in example 8.2 were cloned and transformed simultaneously by in vivo recombination.
Example 8
Medium Scale Expression of Native and Modified Family 6 Cellulases in Yeast
[0121] One isolated colony of BJ3505 yeast containing YEpFLAG-ΔKpn10-cbh2 was used to inoculate 5 mL of liquid SC-trp in a 20 mL test-tube. After an overnight incubation at 30° C. and 250 rpm, optical density at 600 m was measured and 50 mL of YPEM liquid media in a 250 mL Erlenmeyer flask was inoculated with the amount of yeast required to get a final OD 600 of 0.045. After 72 h of incubation at 30° C. and 250 rpm, supernatant was harvested with a 5 minutes centrifugation step at 3,000×g. The BJ3505 strains expressing the TrCel6A variants, wild-type HiCel6A and variant, wild-type PcCel6A and variant as well as the empty YEpFLAG-1 vector were cultured the same way.
[0122] SC-trp liquid media contains the same components as the SC-trp plate mentioned in example 7 without the agar. YPEM liquid media contains:
Component per Liter Yeast Extract (BD) 10 g Peptone (BD) 5.0 g Glucose (Fisher) 10 g Glycerol (Fisher) 30 mL
Example 9
Characterization of Modified Family 6 Cellulases from Yeast Culture Supernatants
[0000] 9.1 Comparison of the thermophilicity of the Modified TrCel6A with the Native TrCel6A.
[0123] The thermophilicity of each enzyme was determined by measuring the release of reducing sugars from a soluble β-glucan substrate at different temperatures. Specifically, in a 300 μL PCR plate, 50 μL of crude supernatant obtained as per Example 9 was mixed with 50 μL of pre-heated 1% (w/v) β-glucan (Barley, Medium Viscosity; Megazyme) in 55 mM sodium citrate pH 5.0 in 10 different columns of a 96-well PCR plate. Mixtures were incubated for 30 min. at 10 different temperatures of a gradient (56, 58.1, 59.8, 62.6, 66, 70, 73.4, 76.2, 78.1 and 80° C.) then released reducing sugars were measured as follows: 100 μL of DNS reagent was added to each well and the plate was incubated 20 minutes at 95° C.
[0124] DNS reagent contains:
Component g/L 3,5-Dinitosalicylic acid (Acros) 10 Sodium hydroxide (Fisher) 10 Phenol (Sigma) 2 Sodium metabisulfate (Fisher) 0.5
[0125] Once the temperature decreased below 40° C., 135 μL of each reaction mixture was transferred to individual wells of a 96-well microplate containing 65 μL of Rochelle salts (40% Sodium potassium tartrate) in each well and OD 560 was measured using a Fluostar Galaxy microplate reader equipped with a 560 nm filter. Blank value was measured by treating the supernatant from the strain carrying the empty vector the same way and was subtracted to each value. Then activity was expressed in percentage relatively to the highest value of the four parameters Polynomial fit for each variant except variant TrCel6A-G231S-N305S-R410Q-S413P for which a four parameters Log Normal fit was used ( FIG. 6 ).
[0126] All modified Family 6 cellulases shown an improved optimal temperature when compared to their respective wild-type except variant TrCel6A-G231S-N305S-R40Q-S413P which on the other hand exhibits a broad temperature range with more then 80% of the maximum activity ( FIG. 6 ). Among all TrCel6A variants, TrCel6A-S413P has the higher optimal temperature at 72.2° C., an increase of 5.6° C. compared to wild-type TrCel6A ( FIG. 6 a ). PcCel6A-S407P and HiCel6A-Y420P also exhibit an increase in optimal temperature when compared to their respective wild-type ( FIGS. 6 b and c ).
[0000] 9.2 Comparison of the Alkalophilicity of the Modified TrCel6A with the Native TrCel6A.
[0127] The alkalophilicity of each enzyme was determined by measuring the release of reducing sugars from a soluble β-glucan substrate at different pH. Specifically, in a 300 μL PCR plate, 50 μL of crude supernatant obtained as per example 9 was mixed to 50 μL of pre-heated 1% (w/v) β-glucan (Barley, Medium Viscosity; Megazyme) in 55 mM sodium citrate, 55 mM sodium phosphate pH 3.0, 4.0, 5.0, 5.75, 6.25, 6.75, 7.25 or 8.5 in 8 different columns of the plate (once mixed to the supernatant and heated at 60-65° C., pHs where 3.95, 4.65, 5.65, 6.25, 6.65, 6.95, 7.15 and 7.45 respectively). Mixtures were incubated 30 min. at 65° C. (60° C. for PcCel6A and variant) then released reducing sugars were measured as per Example 10.1. Background activity from the yeast host was measured by treating the supernatant from the strain carrying the empty vector the same way and this activity was subtracted from the activity value for each variant. Then activity was expressed in percentage relatively to the highest value of the three parameter mechanistic fit for each variant ( FIG. 7 ).
[0128] All modified Family 6 cellulases exhibit increased alkalophilicity when compared to their wild-type. For TrCel6A, the most important shift was observed with variants TrCel6A-G231S-R410Q-S413P (+1.25 pH units) followed by TrCel6A-G231S-N305S-R410Q-S413P (+1.01 pH units).
[0000] 9.3 Comparison of the Thermostability of the Modified TrCel6A with the Native TrCel6A.
[0129] The thermostability of each enzyme was determined by measuring the release of reducing sugars from a soluble β-glucan substrate after different pre-incubation time of the supernatant at 60° C. (55° C. for PcCel6A and variant). Specifically, in a 300 μL PCR plate, 50 μL of crude supernatant obtained as per Example 9 was incubated at 60° C. (55° C. for PcCel6A and variant) for 0, 15, 30, 45, 60, 75, 90 and 120 minutes. Then, 50 μL of 1% (w/v) β-glucan (Barley, Medium Viscosity; Megazyme) in 55 mM sodium citrate pH 5.0 was added and mixtures were incubated 30 minutes 65° C. (60° C. for PcCel6A and variant). Released reducing sugars were then measured as per Example 10.1. Background activity from the yeast host was measured by treating the supernatant from the strain carrying the empty vector the same way and this activity was subtracted from the activity value for each variant. Finally, activity was expressed in percentage relatively to the highest value of the three parameter single exponential decay fit for each variant ( FIG. 5 ).
[0130] All TrCel6A variants have shown increased thermostability when compared to wild-type TrCel6A ( FIG. 5 a ). The S413P mutation results in a significant increase in the thermostability TrCel6A. TrCel6A-S413P retains 45% of its activity after 60 minutes at 60° C. whereas TrCel6A retains only 4% of its activity after 60 minutes. This represents a greater improvement in thermostability compared to that of the TrCel6A-S413Y variant disclosed in US Patent Publication No. 20060205042, which retained on average 41% of its activity under similar conditions. The highest improvement was observed with TrCel6A-R410Q-S413P and TrCel6A-G231S-R410Q-S413P as both retain 58 and 60% of their activity after 60 minutes at 60° C. respectively. Similarly to TrCel6A, PcCel6A-S407P retains 38% of its activity after 60 minutes at 55° C. whereas PcCel6A retains only 6% of its activity after 60 minutes ( FIG. 5 b ). This supports the claim for which a proline at the equivalent position of TrCel6A residue 413 increases thermostability.
[0000] 9.4 Comparison of the T 50 of the Modified TrCel6A with the Native TrCel6A.
[0131] T 50 herein is defined as the temperature at which the crude yeast supernatant retains 50% of its β-glucan hydrolyzing activity after 15 minutes of incubation without substrate. It was determined by measuring the release of reducing sugars from a soluble β-glucan substrate after 15 minutes of pre-incubation at different temperatures. Specifically, in a 300 μL PCR plate, 50 μL of crude supernatant obtained as per Example 9, was incubated at 45, 49.2, 53.9, 57.7, 59.5, 60.4, 62.5, 64.2, 66.4, 68.9, 72.7 or 75° C. for 15 minutes. Then, 50 μL of 1% (w/v) β-glucan (Barley, Medium Viscosity; Megazyme) in 55 mM sodium citrate pH 5.0 was added and mixtures were incubated 30 minutes 65° C. (60° C. for PcCel6A and variant). Released reducing sugars were then measured as per Example 10.1. Background activity from the yeast host was measured by treating the supernatant from the strain carrying the empty vector the same way and this activity was subtracted from the activity value for each variant. Finally, activity was expressed in percentage relatively to the highest value of the four parameter sigmoid fit for each variant ( FIG. 4 ).
[0132] The T 50 of the TrCel6A-S413P was determined to be 64.1° C., as compared to 59° C. for the parent TrCel6A ( FIG. 4 a ). This represents an increase in the thermostability by over 5° C. through the introduction of the S413P mutation. This represents a significant improvement in enzyme stability compared to the S413Y mutation disclosed US Patent Publication No. 20060205042, which shows a very modest 0.2-0.3° C. increase in the Tm of the TrCel6A-S413Y over TrCel6A. Although the methods to determine the Tm disclosed US Patent Publication No. 20060205042 is different from the determination of T50 disclosed herein, both methods seek to determine the temperature at which the protein undergoes a significant and structural change that leads to irreversible inactivation. The T 50 of the other TrCel6A variants was at least 3.2° C. higher then wild-type TrCel6A.
[0133] PcCel6A-S407P and Hicel6A-Y420P also have shown an increase in TSO when compared to their respective parent enzyme ( FIGS. 4 b and c ). This also supports the claim for which a proline at the equivalent position of TrCel6A residue 413 increases thermostability in Family 6 cellulases.
Example 10
Making Genetic Constructs Comprising Modified Family 6 Cellulase DNA Sequences
[0000] 10.1 Isolation of Trichoderma reesei Genomic DNA and Construction of T. reesei Genomic Libraries
[0134] A strain of Trichoderma reesei obtained derived from RutC30 (ATCC #56765; Montenecourt, B. and Eveleigh. D. 1979 . Adv. Chem. Ser. 181: 289-301) comprising a disrupted native TrCel6A gene was used. RutC30 is derived from Trichoderma reesei Qm6A (ATCC # 13631; Mandels, M. and Reese, E. T. 1957 . J. Bacteriol. 73: 269-278). It is well understood by those skilled in the art that the procedures described herein, the genetic constructs from these strains, and the expression of the genetic constructs in these strains are applicable to all Trichoderma strains derived from Qm6A.
[0135] To isolate genomic DNA, 50 mL of Potato Dextrose Broth (Difco) was inoculated with T. reesei spores collected from a Potato Dextrose Agar plate with a sterile inoculation loop. The cultures were shaken at 200 rpm for 2-3 days at 28° C. The mycelia was filtered onto a GFA glass microfibre filter (Whatman) and washed with cold, deionized water. The fungal cakes were frozen in liquid nitrogen crushed into a powder with a pre-chilled mortar and pestle; 0.5 g of powdered biomass was resuspended in 5 mL of 100 mM Tris, 50 mM EDTA, pH 7.5 plus 1% sodium dodecyl sulphate (SDS). The lysate was centrifuged (5000 g for 20 min, 4° C.) to pellet cell debris. The supernatant was extracted with 1 volume buffer (10 mM Tris, 1 mM EDTA, pH 8.0) saturated phenol followed by extraction with 1 volume of buffer-saturated phenol:chloroform:isoamyl alcohol (25:24:1) in order to remove soluble proteins. DNA was precipitated from the solution by adding 0.1 volumes of 3 M sodium acetate, pH 5.2 and 2.5 volumes of cold 95% ethanol. After incubating for at least 1 h at −20° C., the DNA was pelleted by centrifugation (5000 g for 20 min, 4° C.), rinsed with 10 mL 70% ethanol, air-dried and resuspended in 1 mL 10 mM Tris, 1 mM EDTA, pH 8.0. RNA was digested by the addition of Ribonuclease A (Roche Diagnostics) added to a final concentration of 0.1 mg/mL and incubation at 37° C. for 1 hour. Sequential extractions with 1 volume of buffer-saturated phenol and 1 volume of buffer-saturated phenol:chloroform:isoamyl alcohol (25:24:1) was used to remove the ribonuclease from the DNA solution. The DNA was again precipitated with 0.1 volumes of 3 M sodium acetate, pH 5.2 and 2.5 volumes of cold 95% ethanol, pelleted by centrifugation, rinsed with 70% ethanol, air-dried and resuspended in 50 μL of 10 mM Tris, 1 mM EDTA, pH 8.0. The concentration of DNA was determined by measuring the absorbance of the solution at 260 nm (p. C1 in Sambrook et al., Molecular Cloning: A Laboratory Manual, Second Edition, Cold Spring Harbor Press 1989, which is incorporated herein by reference, and hereafter referred to as Sambrook et al.).
[0136] Two plasmid libraries and one phage library were constructed using genomic DNA isolated from T. reesei strain M2C38. The plasmid libraries were constructed in the vector pUC119 (Viera and Messing, Methods Enzymol. 153:3, 1987) as follows: 10 μg genomic DNA was digested for 20 hrs at 37° C. in a 100 μL volume with 2 units/μg of BamH1 or EcoR1 restriction enzymes. The digested DNA was fractionated on a 0.75% agarose gel run in 0.04 M Tris-acetate, 1 mM EDTA and stained with ethidium bromide. Gel slices corresponding to the sizes of the genes of interest (based on published information and Southern blots) were excised and subjected to electro-elution to recover the DNA fragments (Sambrook et al., pp. 6.28-6.29). These enriched fractions of DNA were ligated into pUC119 in order to create gene libraries in ligation reactions containing 20-50 μg/mL DNA in a 2:1 molar ratio of vector:insert DNA, 1 mM ATP and 5 units T4 DNA ligase in a total volume of 10-15 μL at 4° C. for 16 h. Escherichia coli strain HB101 was electroporated with the ligation reactions using the Cell Porator System (Gibco/BRL) following the manufacturer's protocol and transformants selected on LB agar containing 70 μg/mL ampicillin.
[0137] The phage library was constructed in the vector λDASH (Stratagene, Inc.) as follows: genomic DNA (3 μg) was digested with 2, 1, 0.5 and 0.5 units/μg BamHI for 1 hour at 37° C. to generate fragments 9-23 kB in size. The DNA from each digest was purified by extraction with 1 volume Tris-staturated phenol:choroform:isoamyl alcohol (25:24:1), followed by precipitation with 10 μL 3 M sodium acetate, pH 5.2 and 250 μl 95% ethanol (−20° C.). The digested DNA was pelleted by microcentrifugation, rinsed with 0.5 mL cold 70% ethanol, air-dried and resuspended in 10 μL sterile, deionized water. Enrichment of DNA fragments 9-23 kB in size was confirmed by agarose gel electrophoresis (0.8% agarose in 0.04 M Tris-acetate, 1 mM EDTA). Digested DNA (0.4 μg) was ligated to 1 μg λDASH arms predigested with BamHI (Stratagene) in a reaction containing 2 units T4 DNA ligase and 1 mM ATP in a total volume of 5 μl at 4° C. overnight. The ligation mix was packaged into phage particles using the GigaPack® II Gold packaging extracts (Stratagene) following the manufacturer's protocol. The library was titred using the E. coli host strain XL1-Blue MRA (P2) and found to contain 3×10 5 independent clones.
[0000] 10.2 Cloning the Cellobiohydrolase I (cbh1) and Cellobiohydrolase II (cbh2) Genes from pUC119 Libraries
[0138] E. coli HB101 transformants harboring cbh1 or cbh2 clones from recombinant pUC119-BamH1 or -EcoRI libraries were identified by colony lift hybridization: 1−3×10 4 colonies were transferred onto HyBond™ nylon membranes (Amersham); membranes were placed colony-side up onto blotting paper (VWR 238) saturated with 0.5 M NaOH, 1 M NaCl for 5 min to lyse the bacterial cells and denature the DNA; the membranes were then neutralized by placing them colony-side up onto blotting paper (VWR 238) saturated with 1.5 M Tris, pH 7.5 plus 1 M NaCl for 5 min; the membranes were allowed to air-dry for 30 min and the DNA was then fixed to the membranes by baking at 80° C. for 2 h.
[0139] 32 P-labelled probes were prepared by PCR amplification of short (0.7-1.5 kB) fragments of the cbh1 and cbh2 coding regions from the enriched pool of BamH1 or EcoR1 fragments, respectively, in a labelling reaction containing 10-50 ng target DNA, and 0.2 mM each of d(GCT)TP, 0.5 μM dATP, 20-40 μCi α- 32 P-dATP, 10 pmole oligonucleotide primers and 0.5 units Taq polymerase in a total volume of 20 μL. The reaction was subjected to 6-7 cycles of amplification (95° C., 2 min; 56° C., 1.5 min; 70° C., 5 min). The amplified, 32 P-labelled DNA was precipitated by the addition of 0.5 mL 10% (w/v) trichloroacetic acid and 0.5 mg yeast tRNA. The DNA was pelleted by microcentrifugation, washed twice with 1 mL 70% ethanol, air-dried and resuspended in 1 M Tris pH 7.5, 1 mM EDTA.
[0140] Nylon membranes onto which the recombinant pUC119 plasmids had been fixed were prehybridized in heat-sealed bags for 1 h at 60-65° C. in 1 M NaCl, 1% SDS, 50 mM Tris, 1 mM EDTA pH 7.5 with 100 μg/mL denatured sheared salmon sperm DNA. Hybridizations were performed in heat-sealed bags in the same buffer with only 50 μg/mL denatured sheared salmon sperm DNA and 5×10 6 -5×10 7 cpm of denatured cbh1 or cbh2 probe for 16-20 h at 60-65° C. Membranes were washed once for 15 min with 1 M NaCl, 0.5% SDS at 60° C., twice for 15 min each with 0.3M NaCl, 0.5% SDS at 60° C. and once for 15 min with 0.03M NaCl, 0.5% SDS at 55° C. Membranes were again placed in heat-sealed bags and exposed to Kodak RP X-ray film to 16-48 h at −70° C. The X-ray film was developed following the manufacturer's protocols. Colonies giving strong or weak signals were picked and cultured in 2×YT media supplemented with 70 μg/mL ampicillin. Plasmid DNA was isolated from these cultures using the alkaline lysis method (Sambrook, et al., pp. 1.25-1.28) and analyzed by restriction digest, Southern hybridization (Sambrook, et al., pp. 9.38-9.44) and PCR analysis (Sambrook, et al., pp. 14.18-14,19).
[0141] Clones carrying the cbh1 gene were identified by colony lift hybridization of the pUC119-BamH1 library with a 0.7 kb cbh1 probe prepared using oligonucleotide primers designed to amplify bp 597-1361 of the published cbh1 sequence (Shoemaker et al., Bio/Technology 1: 691-696, 1983; which is incorporated herein by reference). A cbh1 clone, pCOR132, was isolated containing a 5.7 kb BamH1 fragment corresponding to the promoter (4.7 kb) and 1 kb of the cbh1 structural gene (2.3 kb). From this, a 2.5 kb EcoR1 fragment containing the cbh1 promoter (2.1 kb) and 5′ end of the cbh1 coding region (0.4 kb) was subcloned into pUC119 to generate pCB152. Clones carrying the cbh2 gene were identified by colony lift hybridization of the pUC119-EcoR1 library with a 1.5 kb cbh2 probe prepared using oligonucleotide primers designed to amplify bp 580-2114 of the published cbh2 sequence (Chen et al. Bio/Technology 5: 274-278, 1987). A cbh2 clone, pZUK600 was isolated containing a 4.8 kb EcoR1 fragment corresponding to the promoter (600 bp), structural gene (2.3 kb) and terminator (1.9 kb).
[0000] 10.3 Cloning Xylanase II (xln2) gene from λDASH Libraries
[0142] Digoxigen-11-dUTP labelled probes were prepared from PCR amplified coding regions of the xln2 gene by random prime labeling using the DIG Labeling and Detection kit (Roche Diagnostics) and following the manufacturer's protocols. Genomic clones containing the xln2 gene were identified by plaque-lift hybridization of the λDASH library. For each gene of interest, 1×10 4 clones were transferred to Nytran® (Schleicher and Schull) nylon membranes. The phage particles were lysed and the phage DNA denatured by placing the membranes plaque-side up on blotting paper (VWR238) saturated with 0.5 M NaOH, 1 M NaCl for 5 min. The membranes were then neutralized by placing them plaque-side up onto blotting paper saturated with 1.5 M Tris, pH 7.5 plus 1 M NaCl for 5 min and subsequently allowed to air-dry for 30 min. The DNA was then fixed to the membranes by baking at 80° C. for 2 h. The membranes were prehybridized in heat-sealed bags in a solution of 6×SSPE, 5×Denhardt's, 1% SDS plus 100 μg/mL denatured, sheared salmon sperm DNA at 65° C. for 2 h. The membranes were then hybridized in heat-sealed bags in the same solution containing 50 μg/mL denatured, sheared salmon sperm DNA and 0.5 μg of digoxigen-dUTP labelled probes at 65° C. overnight. The membranes were washed twice for 15 min in 2×SSPE, 0.1% SDS at RT, twice for 15 min in 0.2×SSPE, 0.1% SDS at 65° C. and once for 5 min in 2×SSPE. Positively hybridizing clones were identified by reaction with an anti-digoxigenin/alkaline phosphatase antibody conjugate, 5-bromo-4-chloro-3-indoyl phosphate and 4-nitro blue tetrazolium chloride (Roche Diagnostics) following the manufacturer's protocol. Positively hybridizing clones were further purified by a second round of screening with the digoxigen-dUTP labelled probes.
[0143] Individual clones were isolated and the phage DNA purified as described in Sambrook et al. pp. 2.118-2.121 with the exception that the CsCl gradient step was replaced by extraction with 1 volume of phenol:choroform:isoamyl alcohol (25:24:1) and 1 volume of chloroform:isoamyl alcohol (24:1). The DNA was precipitated with 0.1 volumes of 3 M sodium acetate, pH 5.2 and 2.5 volumes cold 95% ethanol. The precipitated phage DNA was washed with 0.5 mL cold 70% ethanol, air-dried and resuspended in 50 μL 10 mM Tris, 1 mM EDTA pH 8.0. Restriction fragments containing the genes of interest were identified by restriction digests of the purified phage DNA and Southern blot hybridization (Sambrook, et al., pp. 9.38-9.44) using the same digoxigen-dUTP labelled probes used to screen the λDASH library. The membranes were hybridized and positively hybridizing fragments visualized by the same methods used for the plaque lifts. Once the desired restriction fragments from each λDASH clone were identified, the restriction digests were repeated, the fragments were resolved on a 0.8% agarose gel in TAE and the desired bands excised. The DNA was eluted from the gel slices using the Sephaglas B and Prep Kit (Pharmacia) following the manufacturer's protocol.
[0144] Clones carrying the xln2 gene were identified by colony lift hybridization of the λDASH library (Example 7) with a xln2 probe comprising bp 100-783 of the published xln2 sequence (Saarelainen et al., Mol. Gen. Genet. 241: 497-503, 1993). A 5.7 kb Kpn1 fragment containing the promoter (2.3 kb), coding region (0.8 kb) and terminator (2.6 kb) the xln2 gene was isolated by restriction digestion of phage DNA purified from a λDASH xln2 clone. This fragment was subcloned into the Kpn1 site of pUC119 to generate the plasmid pXYN2K-2.
[0000] 10.4: Construction of a Vector Directing the Expression of Modified Family 6 Cellulase in Trichoderma reesei.
[0145] A 2.3 kb fragment containing the promoter and secretion signal of the xln2 gene (bp −2150 to +99 where +1 indicates the ATG start codon and +97-99 represent the first codon after the TrXyl11 secretion signal peptide) was amplified with Pwo polymerase from the genomic xln2 subclone pXYN2K-2 (Example 7) using an xln2-specific primer containing a NheI directly downstream of the Gln at codon 33 and the pUC reverse primer (Cat. No. 18432-013, Gibco/BRL) which anneals downstream of the Kpn1 site at the 5′ end of the xln2 gene. This xlz2 PCR product was inserted as a blunt-ended fragment into the SmaI site of the pUC119 polylinker in such an orientation that the BamHI site of the polylinker is 3′ to the NheI site; this generated the plasmid pUC/XynPSS(Nhe). The same xln2 PCR product was reisolated from pUC/XynPSS(Nhe) by digestion with EcoRI (which was amplified as part of the pUC119 polylinker from pXYN2K-2) and BamHI and inserted into the plasmid pBR322L (a derivative of pBR322 containing an Sph1-Not1-Sal1 adaptor between the original Sph1 and Sal1 sites at bp 565 and 650), also digested with EcoRI and BamHI, to generate the plasmid pBR322LXN. To facilitate high level expression of the modified xylanases, a 1.3 kb HindIII fragment comprising bp −1400 to −121 of the xln2 promoter in pBR322LXN was replaced with a 1.2 kb HindIII fragment comprising bp −1399 to −204 of the cbh1 promoter which was isolated by HindIII digestion of pCOR132; this generated the plasmid pBR322LC/XN. Finally, the EcoR1 site of pBR322LXC was then blunted with Klenow and Spe1 linkers (Cat. No. 1086, New England Biolabs) were added to generate pBR322SpXC.
[0146] A fragment containing the TrCel6A-S413P gene was isolated from the YEpFLAGΔKpn10-cbh2 vector (described in Example 6 above) by digestion with NheI and KpnI inserted into pCB219N-N digested with NheI and BamHI to generate pS413P/C2ter. To make pCB219N-N, a cbh2 terminator fragment was amplified from the pZUK600 (described in Example 7, above) template using a primer homologous to bp 2226-2242 of the published 3′ untranslated region of the cbh2 gene (Chen et al., 1987) containing a short polylinker comprising XbaI-NheI-BamHI-SmaI-KpnI sites at the 5′ end and the pUC forward primer (Cat. No. 1224, New England Biolabs) which anneals upstream of the EcoR1 site at the 3′ end of cbh2 in pZUK600. This fragment was digested at the engineered XbaI and EcoRI sites and inserted into the corresponding sites of pUC119 to generate pCB219. An EcoR1-Not1 adaptor (Cat. No. 35310-010, Gibco/BRL) was inserted into the unique EcoR1 site of pCB219 to generate pCB219N. A fragment comprising the TrCel6A gene and the cbh2 terminator was isolated from pS413P/C2ter by digestion with NheI and NotI and inserted into pBR322SpXC digested with NheI and NotI to generate the expression cassette pc/xS413P-EC.
[0147] The selection cassette containing plasmid, pNCBgINSNB(r), was derived from a N. crassa pyr4 containing plasmid, pFB6 (Radford, A., Buston, F. P., Newbury, S. F. and Glazebrook, J. A. (1985) Regulation of pyrimidine metabolism in Neurospora . In Molecular Genetics of Filamentous Fungi (Timberlake, W. E., editor), Alan R. Liss (New York), pages 127-143). A 3.2 kb BglII fragment from pFB6 containing the N. crassa pyr4 gene (GenBank accession M13448) as well as its promoter, terminator and some 5′ UTR sequences was cloned into the BamHI site of pUC119 modified to contain NotI, SmaI, NheI and BglII sites in the polylinker (between EcoRI and SacI) to generate pNCBgl-NSNB(r). An SpeI/NotI fragment comprising the TrCel6A-S413P gene operably linked to the cbh1 promoter, xln2 secretion signal peptide and cbh2 transcriptional terminator was isolated from the expression cassette vector pc/xS413P-EC and inserted into pNCBgl-NSNB(r) digested with NheI (SpeI and NheI having compatible 5′ overhanging sequences) and NotI to generate p c / x -S413P-TV. This final construct was linearized by NotI prior to transformation of Trichoderma reesei.
Example 11
Transformation of the Trichoderma reesei
[0000] 11.1 Isolation of pyr4 Auxotrophs
[0148] In order to use the N. crassa pyr4 gene as a selectable marker, a spontaneous pyr4 auxotroph was isolated as follows: 1×10 6 spores of T. reesei were plated onto minimal media containing 5 mM uridine and 0.15% (w/v) of the uridine analog 5-fluoroorotic acid (FOA) as previously described for the selection of pyr4 auxotrophs of T. reesei (Berges, T. and Barreau, C. 1991 Curr Genet. 19(5):359-65). The ability to grow on FOA-containing media will allow for selection of mutants disrupted in either the pyr2 gene encoding orotate phosphoribosyl transferase or the pyr4 gene encoding orotidine 5′-phosphate decarboxylase. Spontaneous FOA-resistant colonies were subjected to secondary selection of minimal media with and without uridine. Spores of FOA-resistant colonies that could not grow on minimal media were then transformed with pNCBglNSNB(r) (described in Example 11.4) and selected for growth on minimal media. Only those strains that were complemented by the N. crassa pyr4 gene in pNCBgINSNB(r) will grow on minimal media and are true pyr4 auxotrophs. Using these procedures, a stable pyr4 auxotroph of T. reesei was obtained.
[0000] 11.2 Transformation of Protoplasts of T. reesei pyr4 Auxotrophs.
[0149] 5×10 6 spores of T. reesei were plated onto sterile cellophane on Potato Dextrose agar supplemented with 5 mM uridine and are incubated for 20 hours at 30° C. to facilitate spore germination and mycelial growth. Cellophane discs with mycelia were transferred to 10 mL of a protoplasting solution containing 7.5 g/L Driselase and 125 units of protease free β-glucanase (InterSpex Products Inc., Cat. Nos. 0465-1 and 0410-3, respectively) in 50 mM potassium phosphate buffer, pH 6.5 containing 0.6 M ammonium sulfate (Buffer P). The mycelial mat was digested for 5 hours with shaking at 60 rpm. Protoplasts were separated from undigested mycelia by filtration through sterile No. 30 MIRACLOTH™ and collected into a sterile 50 mL round-bottom centrifuge tube and recovered by centrifugation at 1000-1500×g for 10 min at room temperature. Protoplasts were washed with 5 mL of Buffer P and centrifuged again at 1000-1500×g for 10 min at room temperature. Protoplasts were resuspended in 1 mL of STC buffer (1.2 M sorbitol, 10 mM CaCl 2 , 10 mM Tris-HCL, pH 7.5). For transformation, 0.1 mL of resuspended protoplasts were combined with 10 μg of vector DNA and 25 μL of PEG solution (25% PEG 4000, 50 mM CaCl 2 , 10 mM Tris-HCl, pH 7.5). After incubation in an ice water bath for 30 min, 1 mL of PEG solution was added and the mixture incubated for 5 min at room temperature. Transformation mix was diluted with 2 mL of 1.2 M sorbitol in PEG solution and the entire mix was added to 25 mL of molten MMSS agar media (see below) cooled to about 47° C. and the protoplast suspension poured over MMSS agar. Plates were incubated at 30° C. until colony growth was visible. Transformants were transferred to individual plates containing MM agar and allowed to sporulate. Spores were collected and plated at high dilution on MM agar to isolate homokaryon transformants, which were then plated onto PDA to allow for growth and sufficient sporulation to inoculate the screening cultures as described in Example 13 below.
[0150] Minimal medium (MM) agar contains the following components:
Reagent Per L KH 2 PO 4 10 g (NH 4 ) 2 SO 4 6 g Na 3 Citrate•2H 2 O 3 g FeSO 4 •7H 2 O 5 mg MnSO 4 •H 2 O 1.6 mg ZnSO 4 •7H 2 O 1.4 mg CaCl 2 •2H 2 O 2 mg Agar 20 g 20% Glucose f.s. 50 mL 1 M MgSO 4 •7H 2 O f.s. 4 mL pH to 5.5
[0151] MMSS agar contains the same components as MM agar plus 1.2 M sorbitol, 1 g/L YNB (Yeast Nitrogen Base w/o Amino Acids from DIFCO Cat. No. 291940) and 0.12 g/L amino acids (-Ura DO Supplement from BD Biosciences Cat. No. 630416).
Example 12
Production of Modified Family 6 Cellulases in Liquid Cultures
[0152] Individual colonies of Trichoderma were transferred to PDA plates for the propagation of each culture. Sporulation was necessary for the uniform inoculation of the micro-cultures used in testing the ability of the culture to produce the modified TrCelA. variants with increased thermostability. The culture media is composed of the following:
Component g/L (NH 4 ) 2 SO 4 12.7 KH 2 PO 4 8.00 MgSO 4 •7H 2 O 4.00 CaCl 2 •2H 2 O 1.02 Corn Steeped Liquor 5.00 CaCO 3 20.00 Carbon source** 30-35 Trace elements* 2 mL/L
*Trace elements solution contains 5 g/L FeSO 4 .7H 2 0; 1.6 g/L MnSO 4 .H 2 0; 1.4 g/L ZnSO 4 .7H 2 0. ** glucose, Solka floc, lactose, cellobiose, sophorose, corn syrup, or Avicel. The carbon source can be sterilized separately as an aqueous solution at pH 2 to 7 and added to the remaining media initially or through the course of the fermentation.
[0155] Individual transformants were grown in the above media in 1 mL cultures in 24-well micro-plates. The initial pH was 5.5 and the media sterilized by steam autoclave for 30 minutes at 121° C. prior to inoculation. For both native and transformed cells, spores were isolated from the PDA plates, suspended in water and 10 4 -10 5 spores per mL were used to inoculate each culture. The cultures were shaken at 500 rpm at a temperature of 30° C. for a period of 6 days. The biomass was separated from the filtrate containing the secreted protein by centrifugation at 12,000 rpm. The protein concentration was determined using the Bio-Rad Protein Assay (Cat. No. 500-0001). Expression of TrCelA-S413P was determined as described in Example 14.
Example 13
Characterization of T. reesei Culture Filtrates Comprising Modified Family 6 Cellulases
[0156] The expression of TrCel6A-S413P in culture filtrates of T. reesei transformants was determined by Western blot hybridization of SDS-PAGE gels. Specifically, equal amounts of total secreted protein in 10-20 μL of culture filtrate from the TrCel6A-S413P transformants, the parent strain P107B and a strain expressing the native, unmodified TrCel6A (strain BTR213) were added to an equal volume of 2× Laemmli buffer (0.4 g SDS/2 mL glycerol/1 mL 1M Tris-HCl, pH 6.8/0.3085 g DTT/2 mL 0.5% bromophenol blue/0.25 mL β-mercaptoethanol/10 mL total volume). 10 uL of each prepared sample was resolved on a 10% SDS polyacrylamide gel using 24 mM Tris, 192 mM glycine pH 6.8, 10 mM SDS as running buffer. The separated proteins were transferred electrophoretically from the acrylamide gel to a PVDF membrane, prewetted with methanol, in 25 mM Tris/192 mM glycine buffer containing 20% methanol. The membrane was subsequently washed in 30 mL of BLOTTO buffer (5% skim milk powder in 50 mM Tris-HCl, pH 8.0). The membrane was probed with 30 mL of a 1:20,000 dilution of polyclonal antibodies specific to TrCel6A in BLOTTO overnight at room temperature, washed twice more for 10 min with an equal volume of BLOTTO at room temperature, then probed for 1 hour with a 1:3000 dilution of goat anti-rabbit/alkaline phosphatase conjugate in BLOTTO at room temperature. Finally, the membrane was washed twice for 15 min each at room temperature with an excess of 50 mM Tris-HCl, pH 8.0. Hybridizing complexes containing TrCel6A were visualized by treatment of the membrane with 10 mL of a 100 mM NaCl/100 mM Tris-HCl, pH 9.5 buffer containing 45 μl of 4-nitro blue tetrazolium chloride (Roche Diagnostics) and 35 μL of 5-bromo-4-chloro-3-indoyl phosphate (Roche Diagnostics) at room temperature until bands were clearly visible. Positively hybridizing bands of ˜60 kDa were observed in the culture filtrates from most transformants, the positive control strain BTR213, but not from the culture filtrate from strain P107B. Transformant P474B expresses and secretes approximately the same level of TrCel6A-S413P as the amount of unmodified TrCel6A expressed and secreted by the control strain BTR213.
[0157] The stability of the Trichoderma cellulases containing TrCel6A or TrCel6A-S413P was assessed incubation of the cellulases in 50 mM citrate buffer, pH 4.8 at 50° C. for up to 96 hours and then measuring the residual activity of the cellulase by nephelometry (Enari, T. M. and Niku-Paavola M. L. 1988. Meth. Enzym. 160: 117-126).
[0158] While the rate of cellulose hydrolysis by the untreated TrCel6A and TrCel6A-S413P cellulases was identical, after incubation for up to 96 hours in the absence of substrate, the TrCel6A-S413P cellulase maintained much higher activity than the TrCel6A cellulase ( FIG. 8 ). Thus, improvements in the thermostability of TrCel6A also improved the thermostability of a whole Trichoderma cellulase system comprising the modified Family 6 cellulase and other components.
[0159] The present invention has been described with regard to preferred embodiments. However, it will be obvious to persons skilled in the art that a number of variations and modifications can be made without departing from the scope of the invention as described herein.
[0160] All references and citations are herein incorporated by reference.
REFERENCES
[0000]
Ai, Y. C. and Wilson, D. B. 2002. Enzyme Microb. Technol. 30:804-808.
Atomi, H. 2005. Curr. Opin. Chem. Biol. 9:166-173.
Berges, T. and Barreau, C. 1991 Curr Genet. 19(5):359-65
Bhat, M. K. 2000. Biotechnol. Adv. 18:355-383.
Butler, T. and Alcalde, M. 2003. In Methods in Molecular Biology, vol. 231: (F. H. Arnold and G. Georgiou, editors), Humana Press Inc. Totowa (New Jersey), pages 17-22.
Chica, R. A., et al. 2005. Curr. Opin. Biotechnol. 16:378-384.
Claeyssens, M. and Henrissat, B. 1992, Protein Science 1: 1293-1297).
Claeyssens, M., et al. 1997. Eds.; The Royal Society of Chemistry, Cambridge.
Davies, G. J., et al. 2000. Biochem. J. 348:201-207.
Eijsink, V. G., et al. 2004. J. Biotechnol. 113:105-20.
Eijsink V G, et al. 2005. Biomol. Eng. 22:21-30.
Foreman, P. K., et al. 2003. J. Biol. Chem. 278:31988-31997.
Gietz, R. D. and Woods, R. A. 2002. Meth. Enzym. 350: 87-96.
Gray, K. A., et al. 2006. Curr. Opin. Chem. Biol. 10:141-146.
Hoffman, C. S., and Winston, F. 1987. Gene 57: 267-272.
Hughes, S. R., et al. 2006. Proteome Sci. 4:10-23.
Lehtio, J., et al. 2003. Proc Natl Acad Sci USA. 100:484-489.
Li, W. F., et al. 2005 Biotechnol. Adv. 23:271-281.
Lin, Y. and Tanaka, S. 2006. Appl. Microbiol. Biotechnol. 69:627-642.
Mathrani, I. and Ahring, B. K. 1992 Appl. Microbiol. Biotechnol. 38:23-27.
Meinke, A., et al. 1995. J. Biol. Chem. 270:4383-4386.
Radford, A., et al. 1985. In Molecular Genetics of Filamentous Fungi (Timberlake, W. E., editor), Alan R. Liss (New York), pages 127-143
Rouvinen, J., et al. 1990. Science 249:380-386. Erratum in: Science 1990 249:1359.
Saarelainen, R., et al. 1993. Mol. Gen. Genet. 241: 497-503.
Sadeghi, M., et al. 2006. Biophys. Chem. 119:256-270.
Sambrook, et al. 1989. Molecular Cloning: A Laboratory Manual, Second Edition”, Cold Spring Harbor Press
Srisodsuk, M., et al. 1993. J. Biol. Chem. 268:20756-20761.
Spezio, M., et al. 1993. Biochemistry. 32:9906-9916.
Tomme, P., et al. 1988. Eur. J. Biochem 170:575-581.
Varrot, A., et al. 2005. J. Biol. Chem. 280:20181-20184.
Varrot, A., et al. 1999. Biochem. J. 337:297-304.
Vieille, C. and Zeikus, G. J. 2001. Microbiol. Mol. Biol. Rev. 65:1-43.
Viera and Messing 1987. Methods Enzymol. 153:3
von Ossowski, I., et al. 2003. J Mol. Biol. 333:817-829.
Wohlfahrt, G., et al. 2003. Biochemistry. 42:10095-10103.
Zhang S, et al. 2000. Eur. J. Biochem. 267:3101-15. | A modified Family 6 cellulase enzyme comprising a proline residue at position 413 is provided. Genetic constructs and genetically modified microbes comprising DNA sequences encoding the modified Family 6 cellulase are also provided. Family 6 cellulases of the invention display improved thermostability, thermophilicity, alkalophilicity, or a combination thereof, relative to the parent Family 6 cellulases. Such cellulases find use in a variety of applications in industry that require cellulase stability and activities at temperatures, pH values, or both, above that of the native enzyme. | 2 |
BACKGROUND
[0001] The present disclosure generally relates to a surgical apparatus for fusing adjacent bone structures, and, more particularly, to a threaded, barrel-shaped apparatus and method for fusing adjacent vertebrae.
[0002] The fusion of adjacent bone structures is commonly performed to provide for long-term replacement to compensate for vertebral subluxation typically caused by severe trauma to the spine, degenerative or deteriorated bone disorders, e.g., osteoporosis, abnormal curvature of the spine (scoliosis or kyphosis) and/or weak or unstable spine conditions typically caused by infections or tumors. In addition, an intervertebral disc, which is a ligamentous cushion disposed between adjacent vertebrae, may also undergo deterioration or degeneration as a result of injury, disease, tumor or other disorders. The disk shrinks or flattens leading to mechanical instability and painful disc translocations, commonly referred to as a “slipped disc” or “herniated disc”.
[0003] Conventional procedures for disc surgery include partial or total excision of the injured disc portion, e.g., discectomy, and replacement of the excised disc with biologically acceptable plugs or bone wedges. The plugs are driven between adjacent vertebrae to maintain normal intervertebral spacing and to achieve, over a period of time, bony ingrowth or “fusion” with the plug and opposed vertebrae.
[0004] Alternatively, at least one metallic fusion cage may be is inserted within a tapped bore or channel formed in the intervertebral space thereby stabilizing the vertebrae and maintaining a pre-defined intervertebral space. A pair of fusion cages may also be implanted within the intervertebral space. After a period of time, the soft cancellous bone of the surrounding vertebral bone structures infiltrates the cage through a series of apertures disposed within its external wall and unites with bone growth inducing substances disposed within an internal cavity to eventually form a solid fusion of the adjacent vertebrae.
SUMMARY
[0005] The present disclosure relates to a barrel-like fusion implant apparatus for facilitating fusion of adjacent bone structures. The apparatus includes an implant member which is positioned between adjacent opposed bone structures and which defines a longitudinal axis and first and second longitudinal ends. The implant member includes an outer wall dimensioned to engage the opposed bone structures upon positioning therebetween in supporting relation therewith. The outer wall includes at least one thread for facilitating positioning of the implant member between opposing bone structures. Preferably, the implant member also includes an intermediate portion which defines a cross-sectional dimension transverse to the longitudinal axis which is greater than respective cross-sectional dimensions of the first and second longitudinal ends of the implant member.
[0006] The present disclosure also relates to a method of fusing adjacent vertebrae utilizing a barrel-like fusion cage. The method includes the steps of: 1) accessing a space defined between the vertebrae; 2) providing a barrel-like fusion cage as described above; 3) advancing one of the first and second ends of the fusion cage into the space between adjacent vertebrae and positioning the cage in contact with the adjacent vertebrae; and 4) permitting bone ingrowth into contacting surfaces of the fusion cage to facilitate fusion of the adjacent vertebrae.
BRIEF DESCRIPTION OF THE DRAWINGS
[0007] Preferred embodiments of the disclosure are described herein with reference to the drawings wherein:
[0008] [0008]FIG. 1 is a perspective view of a fusion cage according to the present disclosure;
[0009] [0009]FIG. 2 is a side view of the fusion cage shown in FIG. 1;
[0010] [0010]FIG. 3 is a cross-sectional view of the fusion cage taken along section line 3 - 3 of FIG. 2;
[0011] [0011]FIG. 4 is an axial view of the fusion cage of FIG. 1;
[0012] [0012]FIG. 5 is a cross-sectional view of the fusion cage taken along section line 5 - 5 of FIG. 4;
[0013] [0013]FIG. 6A is a lateral view illustrating a pair of cylindrically-shaped prior art fusion implants positioned within the intervertebral space for fusion of adjacent vertebrae;
[0014] [0014]FIG. 6B is a top view showing a side-by-side orientation of two prior art cylindrically-shaped fusion cages between two adjacent vertebrae;
[0015] [0015]FIG. 7A is a lateral view showing the placement of the fusion cage of FIG. 1 between two adjacent vertebrae;
[0016] [0016]FIG. 7B is a top view showing a pair of fusion implants according to the present disclosure positioned within the intervertebral space for fusion of adjacent vertebrae; and
[0017] [0017]FIG. 8 is an axial view detailing insertion of a pair of the implants within the vertebrae.
DETAILED DESCRIPTION
[0018] Referring now to the drawings in which like reference numerals identify similar or identical elements throughout the several views, FIGS. 1 - 5 illustrate the fusion cage implant according to the present disclosure. Fusion cage 10 is contemplated to be a self-tapping implant, i.e., the implant is intended to be inserted within a preformed bore in adjacent bone structures, e.g., adjacent vertebrae, without necessitating tapping of an internal thread within the bone structures prior to insertion. Alternatively, the implant may be inserted within a tapped bore formed in adjacent vertebral bodies as is conventional in the art.
[0019] Fusion implant 10 includes a generally elongated body 12 having a proximal end 13 and a distal end 14 . In the drawings and in the description which follows, the term “proximal”, as is traditional, will refer to the end of the cage 10 which is closer to the surgeon, while the term “distal” will refer to the end which is further from the surgeon. Preferably, cage 10 is fabricated from a suitable biocompatible rigid material such as titanium and/or alloys of titanium, stainless steel, ceramic materials or rigid polymeric materials. Moreover, it is envisioned that cage 10 is sufficient in strength to at least partially replace the supporting function of an intervertebral disc, i.e., to maintain adjacent vertebrae in desired spaced relation, during healing and fusion. Cage 10 is preferably provided in various lengths ranging from about 24 mm to about 28 mm for example.
[0020] As best shown in FIGS. 1 and 3, the body 12 of cage 10 includes an outer wall 15 which encloses an inner cavity 18 defined within the interior of the cage body 12 . Inner cavity 18 accommodates bone chips or bone growth inducing substances as is known in the art to induce the soft cancellous bone surrounding the vertebrae to grow inwardly towards the contact surfaces of the fusion cage 10 to stabilize the cage 10 between two adjacent vertebrae 202 , 204 (FIG. 7A). Outer wall 15 is generally barrel-shaped along a longitudinal axis “A” which extends from proximal end 13 to distal end 14 (FIG. 2) and includes a bulge 19 generally positioned midway therebetween. As explained in more detail below, it is envisioned that the barrel-like shape of cage 10 increases the overall strength and load sharing capacity of the cage 10 , tends to reduce “stiffness” which has been associated with other prior art designs and allows more bone graft substances to be packed into the augmented internal volume of the cage 10 which will further enhance bone fusion.
[0021] Outer wall 15 also includes at least one side cut-out or concave wall surface portion 20 (FIG. 3) which extends parallel to longitudinal axis “A” along outer wall 15 generally from the proximal end 13 to the distal end 17 . Preferably, two side cut-outs 20 are disposed along outer wall 15 in diametrically opposing relation to reduce the effective dimension or diameter of cage 10 transversally relative to longitudinal axis “A”. In either case, the disposition of the side cut-out(s) 20 (FIG. 3) enhance the low profile features of the present disclosure and facilitate insertion between the vertebral bodies 202 , 204 . With reference to FIGS. 3 and 4, side cut-outs 20 of body 12 provide a generally elliptical configuration or appearance to cage 10 defining a major dimension “B” which is greater than a minor dimension “C”. It is envisioned that this configuration provides a greater surface area of the implant so as to facilitate contacting engagement and support of the implant with the adjacent vertebrae 202 , 204 (FIG. 7A). The side cut-outs 20 are disposed along the minor axis “C” to enhance the low profile features of cage 10 and facilitate insertion.
[0022] As best shown in FIG. 5, the major dimension “B” along axis “A” varies from a minimum dimension “B min ” proximate the ends 13 , 14 of cage body 12 to a bulge section 19 having a maximum dimension “B max ” generally disposed midway between ends 13 , 14 along a medial axis “M”. More specifically, body 12 of cage 10 is symmetrically arranged about medial axis “M” whereby the maximum diameter or cross-sectioned dimension B max extends along the medial axis “M” and progressively decreases to the proximal and distal ends 13 , 14 where the cross-sectional diameters or dimensions are substantially equal. As can be appreciated, this gives cage 10 its barrel-like or bulge-like appearance. Preferably, the maximum diameter or dimension “B max ” ranges from about 12 mm to about 20 mm and the minimum diameter or dimension “B min ” ranges from about 13 mm to about 19 mm. In the preferred embodiment, the maximum diameter is 17.5 mm and the minimum diameter is 16 mm. The length is 21 mm. Other dimensions are also contemplated. It is envisioned that dimensioning the cage 10 in this fashion has several distinct advantages: 1) the barrel-like cage is an inherently stronger pressure vessel than a simple cylinder design, i.e., the barrel-like cage has a higher compressive strength, exhibits greater resistance to fatigue and possesses a higher yield load; 2) the barrel-like shape promotes a better anatomical fit between adjacent vertebrae 202 , 204 in both the transverse plane (Compare FIG. 6B with FIG. 7B) and the sagittal plane (Compare FIG. 6A with FIG. 7A); 3) the low profile ends 13 , 14 and the side cut-outs 20 facilitate insertion of the cage 10 and allow two cages 10 to be placed side-by-side with reduced overhang 125 outside the periphery of the vertebral bodies 202 (Compare FIG. 6B with FIG. 7B); and 4) the barrel-like shape of the cage 10 results in an increase in the internal volume of the cage 10 which enables more bone to grow into the cage 10 , thus enhancing bone-to-cage fusion. The barrel cage also exhibits a higher expulsion load, i.e., force required to eject the cage from the intervertebral space.
[0023] With reference to FIGS. 1, 2 and 5 , outer wall 15 also includes an external threaded configuration formed as part of the exterior surface. Preferably, the external threaded configuration of outer wall 15 includes a generally continuous helical thread 16 which assists in advancing cage 10 into a preformed or pre-drilled cavity between adjacent vertebrae 202 , 204 . Thread 16 provides a varying bite across the cage 10 length to facilitate insertion of the cage 10 and enhance retention of the cage 10 once positioned between the vertebral bodies 202 , 204 . Thread 16 is generally helical in shape and includes a self-tapping cutting thread, i.e., the threads are capable of deburring bone material during advancement into the performed channel. Preferably, the thread path is curved along both the major dimension “B” and minor dimension “C” which creates a series non-linear thread segments across the cage 10 . In some cases it may be preferable to curve the thread 16 only along one of the dimensions, e.g., major dimension “B”, depending upon a particular purpose. It is envisioned that the non-linear thread path of the present disclosure will also provide a self-distracting mechanism during the insertion process which is believed to be advantageous to achieving proper disc height. Alternatively, a thread can be tapped in the bone prior to insertion of the cage 10 . As stated above, it is envisioned that cage 10 can be dimensioned such that cage 10 is generally symmetrical about axis “A”, i.e., front-to-end symmetry, which will permit insertion of the cage 10 from either the proximal or distal end 13 , 14 , respectively. In some cases, however, threads 16 can be disposed at an angle relative to axis “A” which will also facilitate insertion of the cage 10 between the vertebral bodies 202 , 204 and enhance retention of the cage 10 once inserted.
[0024] As best shown in FIGS. 1 and 2, a plurality of apertures 22 extend through outer wall 15 of cage body 12 . Apertures 22 are preferably formed by broaching grooves in the internal surface of the internal cavity 18 . The effect of such broaching is to remove material from the valleys between the threads 16 , thus defining the apertures 22 . The advantages of such an arrangement promote immediate bone to bone contact between the vertebral bodies 202 , 204 and the bone inducing substances packed within the internal cavity 18 of the cage body 12 . Such configuration is disclosed in commonly assigned U.S. Pat. Nos. 4,961,740 and 5,026,373, the contents of which are hereby incorporated by reference.
[0025] Preferably, apertures 22 are oriented such that when the cage 10 is inserted between vertebrae, a majority of apertures 22 contact the upper and lower vertebral bone structures 202 , 204 to encourage bony ingrowth through cage body 12 from the vertebral bone structures 202 , 204 . Similarly, the side cut-outs 20 of cage body 102 preferably do not include apertures in order to prevent growth of disc material which might interfere with the overall bone fusing process. Apertures 22 are preferably substantially the same in dimension although it is envisioned that the dimensions of the apertures 22 may vary to provide for more or less bone-to-bone contact depending upon a particular purpose.
[0026] The present disclosure also relates to a method of inserting the barrel-like fusion cage 10 into an intervertebral space “I” defined between adjacent vertebrae 202 , 204 . The method discussed hereinafter will generally relate to an open antero-lateral approach for spinal fusion implant insertion. However, as can be appreciated, other spinal implant procedures are also contemplated, e.g., posterior, direct anterior, etc . . . Laparoscopic approaches are also envisioned.
[0027] Initially, one lateral side of an intervertebral space “I” between the two vertebral bodies 202 , 204 is accessed utilizing appropriate retractors (not shown) to expose the anterior vertebral surface. Thereafter, the retractor is inserted within the intervertebral space “I” from an antero-lateral or oblique position with relation to the vertebral bodies 202 , 204 . Such an approach provides advantages with regard to avoiding vessels and ligaments.
[0028] Upon insertion of the retractor, the vertebral bodies 202 , 204 are distracted whereby the retractor becomes firmly lodged within the intervertebral space “I”. A drilling instrument is now utilized to prepare the disc space and vertebral bodies 202 , 204 for insertion of the fusion cage 10 . Preferably, the cutting depth of drilling instrument can be readily adjusted to correspond to the length of the fusion cage 10 . As can be appreciated, as the drilling instrument is advanced into the intervertebral space “I”, the surrounding soft tissue is sheared and the bone of the adjacent vertebrae 202 , 204 is cut thereby forming a bore which extends into the adjacent vertebrae 202 , 204 .
[0029] The fusion cage 10 is then packed with bone growth inducing substances as in conventional in the art and then mounted on an insertion instrument (not shown) and advanced to a position adjacent the vertebral bodies 202 , 204 . As mentioned above, the non-linear thread configuration of the fusion cage 10 also provides a self-distracting feature which is believed to enhance implantation of the fusion cage 10 and aid in achieving proper disc height.
[0030] Preferably, the insertion instrument includes rotational features which, in turn, cause the fusion cage 10 to rotate and bite into the vertebral bodies 202 , 204 . As mentioned above, it is envisioned that the center thread or bulge 19 as well as the angle of the threads 16 relative to the longitudinal axis “A”, will vary the thread 16 bite during the insertion process which facilitates insertion and retention of the cage 10 . Moreover, the low profile ends 13 and 14 of cage body 12 as well as the side cut-outs 20 will also facilitate insertion and allow two cages to be placed closer together decreasing the likelihood of cage 10 overhang. Continued rotation of the insertion instrument causes cage 10 to self-tap within the preformed bore. Cage 10 is then released from the mounting instrument which is subsequently removed from the disc area.
[0031] Thereafter, a second lateral side of the intervertebral space “I” is accessed and the above-described process is repeated to insert a second cage 10 in lateral side-by-side relation as shown in FIG. 7B. As appreciated, the cages 10 are arranged such that respective side cut-out portions 20 of each cage 10 are disposed in adjacent side-by-side relation. Alternatively, the cages 10 may be positioned such that the curved body 12 of one cage is received within the side cut out 20 of the other cage to further reduce the profile of the implanted cages as depicted in FIG. 8. Such arrangement permits cages 10 , 10 to be placed in closer proximity thereby facilitating insertion of the cages 10 , 10 within the intervertebral space “I”.
[0032] Fusion cages 10 form struts across the intervertebral space “I” to maintain the adjacent vertebrae 202 , 204 in appropriate spaced relation during the fusion process. Over a period of time, the adjacent vertebral tissue communicates through apertures 22 within cages 10 , 10 to form a solid fusion. It is envisioned that the barrel-like shape of each fusion cage 10 is inherently stronger that a cylinder-shaped fusion cage and provides a better anatomical fit between adjacent vertebrae 202 , 204 (Compare FIG. 6B with FIG. 7B).
[0033] From the foregoing and with reference to the various figure drawings, those skilled in the art will appreciate that certain modifications can also be made to the present disclosure without departing from the scope of the same. For example, it is envisioned that a series of apertures could be drilled at one end of the cage 10 which would allow a surgeon to use a smaller tang and smaller drill thereby preserving more of the posterior elements of the spine during the operation.
[0034] While the above description contains many specifics, these specifics should not be construed as limitations on the scope of the disclosure, but merely as exemplifications of preferred embodiments thereof. Those skilled in the art will envision other modifications within the scope and spirit of the claims appended hereto. | A fusion implant apparatus for facilitating fusion of adjacent bone structures includes n implant member for positioning between adjacent opposed bone structures. The implant member defines a longitudinal axis and first and second longitudinal ends and has an outer wall dimensioned to engage the opposed bone structures upon positioning therebetween in supporting relation therewith. The outer wall includes at least one thread for facilitating positioning between the opposed bone structures. The implant member has an intermediate portion which defines a cross-sectional dimension transverse to the longitudinal axis which is greater than respective cross-sectional dimensions of the first and second longitudinal ends of the implant member. | 0 |
BACKGROUND OF THE INVENTION
This invention relates to methods of casting metal in bonded sand grain, gas-permeable, shell molds, for example, those described in Chandley et al. U.S. Pat. No. 4,340,108, which is hereby incorporated by reference, and to apparatus used for such casting methods.
As more fully described in Chandley et al., in such a casting method, the top half of a gas-permeable shell mold may be secured to the opening of a hollow support cylinder whose inner chamber is connected to a vacuum pump. In this way, the vacuum in the cylinder chamber draws molten metal into the mold cavity from a reservoir in which the bottom of the mold has been submerged.
It is desirable that the means for attaching and separating the mold to the cylinder be quick, simple, and reliably repeated in a mass-production procedure.
To attach the mold to the cylinder opening during the casting process, Chandley discloses a pair of spring clips, extending upwardly along the outside of the upper side surfaces of the mold; these clips support the mold against the cylinder in position so that the sealing surfaces of the mold abut sealing surfaces of the cylinder. The clips are made of a metal that is destroyed at casting temperatures, thus freeing the mold to be removed when the vacuum is released.
SUMMARY OF THE INVENTION
The invention features a method of casting metal in a bonded sand grain, gas permeable shell mold in which a vacuum is applied to an external upper mold surface by engaging the mold in the downwardly facing opening of a generally cylindrical vacuum chamber, defined by a chamber wall with a threaded region sized and shaped to snuggly engage a side mold surface. Engagement is effected by forcing the mold into the chamber opening while causing relative rotation of the mold and chamber, as well as apparatus therefor.
In preferred embodiments the cylinder wall engagement region tapers outwardly as it extends downwardly; engagement of the mold and vacuum chamber is effected by maintaining the vacuum chamber stationary while rotating the mold and moving its top surface upwardly into the chamber. Disengagement of the mold from the chamber is effected by activating downwardly extending push rods against the upper mold surface.
The above method is a simple and reliable way to attach a shell mold to a vacuum chamber, that is suitable for a mass-production casting operation.
Other features and advantages of the invention will be apparent from the following description of the preferred embodiment and from the claims.
DESCRIPTION OF THE PREFERRED EMBODIMENT
We first briefly describe the drawings.
FIG. 1 is a diagrammatic side view, partly in section, of a mold and apparatus for casting, in which the vacuum chamber is positioned over the mold, prior to engagement.
FIG. 2 is the apparatus of FIG. 1 showing the vacuum chamber and mold positioned for casting.
FIG. 3 is a bottom view of the mold of FIG. 1.
FIG. 4 is a cross section of a metal part.
FIG. 5 is an cross sectional view of a portion of the apparatus shown in FIG. 1.
FIG. 6 is an enlarged cross sectional view showing the vacuum chamber partially attached to the mold.
FIG. 7 is an enlarged cross sectional view of the mold of FIG. 1 partially submerged beneath the surface of a reservoir of molten metal.
The figures show apparatus for casting metal part 42 in a rigid, self-supporting, gas permeable, low temperature bonded, sand grain mold 26. Mold 26 is generally of the type described in Chandley et al., and reference is made to that patent for details of the mold not discussed here. The mold is generally cylindrical and has a top and bottom half which are joined along parting plane 35. The bottom half has an annular flange 37 which extends radially past the perimeter of the top half of the mold. The mold includes a plurality of cavities 29, each of which corresponds to a site for casting a part 42, and a gate passage 31 for each cavity.
Referring to FIGS. 1 and 2, the casting apparatus includes, in addition to cylindrical mold 26 described above, a cylindrical vacuum chamber 16 with a downwardly facing opening 36. Chamber 16 is defined in part by wall 32 which extends generally downwardly from the perimeter of horizontal disk 17. Disk 17 is attached to the lower end of vertical support arm 14 which has a hollow central passage 15 communicating between chamber 16 and vacuum means not shown.
Arm 14 is arranged to slide vertically through one end of horizontal support arm 10, and the end of arm 10 opposite arm 14 is slidably engaged to housing 12. Both arms 10 and 14 are moved by control apparatus 18 which is governed by a programmable controller.
In FIG. 1, horizontal arm 10 is retracted, so that chamber 16 is positioned above mold 26 which is mounted on rotation table 20 controlled by hydraulic shaft 22 and motor 24. In FIG. 2, horizontal arm 10 is extended, so that chamber 16 and mold 26 (which are now engaged) are positioned over molten metal reservoir 28. A conveyer means 30 is positioned intermediate the rotation table 20 and reservoir 28.
FIGS. 5 and 6 show the engagement of chamber 16 to mold 26 in greater detail, and FIG. 7 shows the immersion of mold 26 in reservoir 28. As best shown in FIGS. 5 and 6, chamber 16 is generally cylindrical and has downwardly extending walls 32 which terminate in a downwardly facing opening 36. The lower portion 38 of wall 32 is threaded, and tapers outwardly very slightly (about 10° with respect to the vertical), as it extends downwardly. The diameter of chamber opening 36 is very slightly greater than the diameter of mold 34.
OPERATION
In operation, the above-described equipment is used as follows.
Mold 26 is formed as described in Chandley et al. It is then transported to a work station and is positioned on a rotating table 20, so that flange 37 is seated in groove 39 in table wall 41, and mold sides 34 extend above the table, as shown in FIG. 5.
Support arm 10 is retracted to position chamber 16 directly over mold 26. As table 20 is rotated about 3 revolutions over a period of 2-3 seconds, hydraulic shaft 22 simultaneously forces the table upwardly to push the top mold surface into opening 36, so that chamber wall 32 is forced over side wall 34 of mold 26. The mold is soft enough so that the chamber threads can cut into sides 34, yet hard enough so those threads will hold the mold in place, and maintain sufficient vacuum to permit the casting procedure described by Chandley--e.g. a vacuum of 1-3 psi. The taper of wall 32 ensures that the wall and mold will be tightly engaged, even when the heat from the mold causes the wall to expand. Because wall 32 is tapered, a small (e.g. about 3/16 inch) portion of the mold may be stripped off during the threading process.
After the mold is threaded to cavity 16, arm 14 is raised and arm 10 is extended to position the mold over reservoir 28. Arm 14 is then dropped to submerge the bottom portion of the mold in molten metal (FIG. 7), while a vacuum is maintained in core 15 and cavity 16 to draw molten metal into mold cavities 29.
After the mold cavities have been filed and a portion of each of the gate passages 31 has solidified, arm 14 is retracted to remove chamber 16 from the molten metal reservoir. Arm 10 is partially retracted, placing the mold directly over conveyor 30. Pneumatically controlled rods 33, which extend through the disk 17, are extended to strip the mold and cast parts from the vacuum chamber and deposit them on conveyor 30.
Other embodiments are within the following claims. | A method of casting metal in a gas permeable shell mold in which a vacuum is applied to an external upper mold surface by engaging the mold in the downwardly facing opening of a generally cylindrical vacuum chamber, defined by a chamber wall with a threaded region sized and shaped to snuggly engage a side mold surface. Engagement is effected by forcing the mold into the chamber opening while causing relative rotation of the mold and chamber. | 1 |
[0001] This invention relates to an animal feeder with an adjustable feed discharge opening thus adjusting the amount of feed which is allowed to pass through the opening.
BACKGROUND OF THE INVENTION
[0002] Various arrangements of animal feeder are provided in which there is a trough into which feed can be deposited from a hopper above the trough. In most cases the feed material to be deposited can vary in particle size and viscosity so that it is often desirable to provide an arrangement which allows an adjustment of the opening through which the material can feed from the hopper into the trough.
[0003] In many cases the opening is provided by a simple shutter at the gap between the Hopper and the trough where the height of the shutter can be adjusted to vary the gap at the bottom of the shutter.
[0004] In U.S. Pat. No. 4,660,508 (Kleinsasser) issued Apr. 28, 1987 is disclosed a feeder which provides a shelf above the trough with the hopper discharging onto the shelf in a manner so that the feed remains on the shelf but can be moved from the shelf to the trough by the animal as required. Feeders of this type have achieved significant commercial success. Adjustment of the height of the shelf is necessary for the purpose of accommodating different types of feed and different feed rates and this is obtained by a hand crank screw which operates with a threaded nut to raise and lower a strap carrying the shelf. The screw is used in adjustment of this device because the deposit of the feed onto the self requires an accurate adjustment of the distance between the shelf and the bottom edge of the hopper so that cruder systems with a less fine adjustment have been rejected.
[0005] In a number of US patents it is known to provide relatively crude adjustment techniques. For example the following patents provide adjustment devices; U.S. Pat. No. 1,719,245 (Smidley) issued Jul. 2, 1929, U.S. Pat. No. 3,552,360 (Nelson) issued Jan. 5, 1971, US Pat. No. 4,242,985 (Freeborn) issued Jan. 6, 1981, U.S. Pat. No. 4,278,049 (Van Dusseldorp) issued Jul. 14, 1981, U.S. Pat. No. 4,351,274 (Pannier) issued Sep. 28, 1982, U.S. Pat. No. 4,462,338 (Thibault) issued Jul. 31, 1984, U.S. Pat. No. 6,408,787 (Clark) issued Jun. 25, 2002.
[0006] It is also known to provide arrangements in which adjustment in a relatively crude manner is effected by selecting one of a plurality of holes in which to locate the pin of an adjustment lever so that the adjustment is effected step by step. As the holes must be necessarily a certain distance apart, such an adjustment provides a relatively crude distance of adjustment so that the fine tuning necessary for determining the specific dimensions of an opening to accurately control the rate of flow of feed material is not possible in such a system. One example is shown in U.S. Pat. No. 6,637,368 (Bondarenko) issued Oct. 28, 2003. This provides a link which extends along one end wall of a feeder and a lever can be moved to place a pin into a selected one of a number of holes in the end wall.
[0007] U.S. Pat. No. 5,603,285 of Kleinsasser issued Feb. 18, 1997 of the present assignees discloses a further similar device where additional adjustment of the height of the shelf is possible but again fine adjustment is provided by a screw.
[0008] U.S. Pat. No. 5,967,083 also of Kleinsasser issued Oct. 19, 1999 of the present assignees discloses a further similar device where additional adjustment of the height of the shelf is possible by extending the strap using a double flap arrangement which folds up or down as required to extend the length of the strap but again fine adjustment is provided by a screw.
[0009] In U.S. Pat. No. 6,923,142 also of Kleinsasser issued Aug. 2, 2005 of the present assignees shows an arrangement which includes a hopper above a shelf onto which feed can fall to be taken by the animal or dropped into a trough below the shelf. The height of the shelf is adjustable to change the width of the opening through which the feed passes to control feed rate. The shelf is carried on straps which extend along the end walls of the hopper and are movable by an adjustment linkage defined by a plate carried on the end wall and a manually adjustable lever mounted for pivotal movement on the plate. The plate has an arcuate outer edge which is serrated to define an arcuate row of saw teeth and the lever is formed by a flat of sheet material which lies in a plane parallel to and slides over the plate and includes a portion thereof which is bent out of a plane of the lever into the plane of the plate which is also serrated with a row of saw teeth shaped to mesh with the saw teeth of the arcuate portion. The portion of the lever is movable in a direction away from the plate a non-meshing position in which the lever is free to move around the pivot axis.
[0010] However this arrangement is provided for fine adjustment of the shelf relative to the bottom edge of the hopper over a limited extent so as to control the release of the feed and the larger adjustment for setting the basic height of the shelf is carried out using the folding flap arrangement disclosed in U.S. Pat. No. 5,967,083 above.
SUMMARY OF THE INVENTION
[0011] It is one object of the invention to provide an improved feeder which allows rapid course adjustment of the height of a shelf between two or more positions and also provides fine adjustment of the opening at each of the course positions to allow a measured amount of feed.
[0012] According to one aspect of the invention there is provided an animal feeder comprising:
[0013] a hopper for containing a feed material to be dispensed to an animal for feeding therefrom;
[0014] a receptacle for receiving the feed from the hopper from which the animal can take the feed;
[0015] the hopper having components of the hopper which co-operate with the receptacle to define an opening through which the feed passes from the hopper to the receptacle so that the amount of feed discharged from the hopper to the receptacle is controlled by a width of the opening;
[0016] the receptacle and the components being mounted for course height adjustment movement between a lowered position of the receptacle and the components for animals when they are at a smaller size and at least one raised position of the receptacle and the components for the animals when they have grown to a larger size;
[0017] one of the receptacle and the components being mounted for fine height adjustment movement to control the width of the opening at both the lowered position and at said least one raised position;
[0018] and an adjustment linkage for operating course height adjustment movement and fine height adjustment movement of said one of the receptacle and the components, the linkage including:
[0019] a manually adjustable lever;
[0020] a link connected to the lever and to an element of the opening such that movement of the lever causes longitudinal movement of the link to effect adjustment of the opening;
[0021] a support for the lever such that the lever is pivotal relative to the support to cause movement off the lever to effect the movement of the link;
[0022] the lever being movable relative to the support between a first position defining said lowered position of the receptacle and the components and said at least one second position defining said at least one raised position of the receptacle and the components;
[0023] in each of the first position and said at least one second position the lever being pivotally adjustable relative to the support to cause said fine adjustment movement.
[0024] Preferably there are only two graduated scales for two pivot positions of the lever for fine adjustment at two course adjusted positions. However but this can increased simply by adding more pivot positions each associated with a graduated scale on an opposite side of the plate.
[0025] It is preferred that the adjustment of the link moves the shelf and the hopper height is adjusted by adding an insert piece which enters between the sides of the bottom neck of the hopper. However the link can adjust the hopper edge with eth shelf being adjusted manually.
[0026] Preferably the lever is movable relative to the support between the first position defining said lowered position of the receptacle and the components and the second position defining the raised position of the receptacle and the components by movement of a pivot point of the lever relative to the support.
[0027] Preferably the pivot point of the lever is moved by lifting the lever off a first pivot pin and moving the lever to a second pivot pin.
[0028] Preferably the lever co-operates in the fine adjustment movement with a graduated scale on the support.
[0029] Preferably there is provided on the support a first graduated scale for co-operation with the lever in the first position and at least one second graduated scale for co-operation with the lever in said at least one second position.
[0030] Preferably the first graduated scale is provided on one side of the support and said at least one second graduated scale on a second opposed side of the support and the pivot point of the lever is rotated in movement from the first position to the second position from one side of the support to the second side of the support.
[0031] Preferably the support comprises a plate defining a surface over which the lever moves, the surface defining an arcuate portion lying on an arc of a circle surrounding the pivot axis of the lever with the graduated scale being located on an edge of the arcuate portion.
[0032] Preferably the arcuate portion of the surface is serrated to define an arcuate row of saw teeth, the lever has a lever edge which is also serrated with a row of saw teeth shaped to mesh with the saw teeth of the arcuate portion and the lever is movable from a meshing position to a non-meshing position in which the lever is free to move around the pivot axis to move the lever and the teeth thereof along the arcuate row of saw teeth to adjust the position of the link.
[0033] Preferably the plate lies in a radial plane of the pivot axis and the arcuate row of teeth are located on an edge of the plate.
[0034] Preferably the edge of the plate is an outer edge facing radially outwardly of the axis.
[0035] Preferably the lever is formed by a flat of sheet material which lies in a plane parallel to and slides over the plate and wherein the lever includes a portion thereof which is bent out of a plane of the lever into the plane of the plate and carries the row of saw teeth of the lever on an edge thereof.
[0036] Preferably the lever is movable in a direction axial of the pivot axis to move the row of teeth thereof axially away from the plate.
[0037] Preferably the link is connected to the lever by a pin which is slidable in a slot in the support and the pin carries a spring which biases the lever into engagement with the support into said meshing position and which is compressible to allow movement of the lever to the non-meshing position and to allow movement of the lever between the first and second positions.
[0038] Preferably the support is mounted on an end wall of the hopper parallel to and spaced from the end wall.
[0039] Preferably the link comprises a strap located between the plate and the end wall.
[0040] Preferably there is provided a trough into which the feed can fall and wherein the receptacle comprises a shelf mounted above the trough arranged so that the animal can take feed from the shelf or can move the feed from the shelf to the trough.
[0041] Preferably the link is connected to the shelf for adjustment of the height thereof relative to a bottom edge of the hopper defining the opening therebetween.
[0042] According to a second more specific definition of the invention there is provided an animal feeder comprising:
[0043] a hopper for containing a feed material to be dispensed to an animal for feeding therefrom;
[0044] a shelf for receiving the feed from the hopper from which the animal can take the feed;
[0045] the hopper having components of the hopper which co-operate with the shelf to define an opening through which the feed passes from the hopper to the shelf so that the amount of feed discharged from the hopper to the shelf is controlled by a width of the opening;
[0046] the shelf being mounted for course height adjustment movement between a lowered position of the shelf for animals when they are at a smaller size and a raised position of the shelf for the animals when they have grown to a larger size;
[0047] the shelf being mounted for fine height adjustment movement to control the width of the opening at both the lowered position and the raised position;
[0048] and an adjustment linkage for operating course height adjustment movement and fine height adjustment movement of the shelf, the linkage including:
[0049] a manually adjustable lever;
[0050] a link connected to the lever and to the shelf such that movement of the lever causes longitudinal movement of the link to effect height adjustment of the shelf;
[0051] a support for the lever such that the lever is pivotal relative to the support to cause movement off the lever to effect the movement of the link;
[0052] the lever being movable relative to the support between a first position defining said lowered position of the shelf and said second position defining said raised position of the shelf;
[0053] in each of the first position and said at least one second position the lever being pivotally adjustable relative to the support to cause said fine adjustment movement.
[0054] According to a third aspect of the invention there is provided an animal feeder comprising:
[0055] a hopper for containing a feed material to be dispensed to an animal for feeding therefrom;
[0056] a shelf for receiving the feed from the hopper from which the animal can take the feed;
[0057] the hopper having components of the hopper which co-operate with the shelf to define an opening through which the feed passes from the hopper to the shelf so that the amount of feed discharged from the hopper to the shelf is controlled by a width of the opening;
[0058] the shelf being mounted for course height adjustment movement between a lowered position of the shelf for animals when they are at a smaller size and a raised position of the shelf for the animals when they have grown to a larger size;
[0059] the shelf being mounted for fine height adjustment movement to control the width of the opening at both the lowered position and the raised position;
[0060] and an adjustment linkage for operating course height adjustment movement and fine height adjustment movement of the shelf;
[0061] wherein the hopper includes a lower pivotal flap member extending along the hopper and arranged to move from a raised position to a lowered position in which it provides said components of the hopper which co-operate with the shelf in the lowered position of the shelf.
[0062] Preferably the hopper in the raised position of the flap member has a bottom edge which co-operates with the shelf in the raised position of the shelf and wherein the pivotal flap member moves from the raised position exposing the bottom edge to the lowered position in which the flap member extends downwardly from the bottom edge to define said components.
[0063] Preferably the pivotal flap member is mounted at each end on a pair of pivot levers pivotally connected to an end wall of the feeder.
BRIEF DESCRIPTION OF THE DRAWINGS
[0064] One embodiment of the invention will now be described in conjunction with the accompanying drawings in which:
[0065] FIG. 1 is a cross sectional view through a feeder according to the present invention showing the shelf in the raised position for larger animals.
[0066] FIG. 2 is a front elevational view on an enlarged scale of the adjustment mechanism of FIG. 1 showing the shelf in the lowered position for smaller animals.
[0067] FIG. 3 is an isometric view on an enlarged scale of the adjustment mechanism of FIG. 1 .
[0068] FIG. 4 is a vertical cross sectional view on an enlarged scale of the adjustment mechanism of FIG. 1 .
[0069] FIG. 5 is a vertical cross sectional view showing on an enlarged scale an adjustment flap member for defining a bottom edge of the hopper in the lowered position of the shelf in the feeder of FIG. 1 , the flap member being shown in the raised position.
[0070] FIG. 6 is a vertical cross sectional view similar to that of FIG. 5 showing the flap member in the raised position.
[0071] In the drawings like characters of reference indicate corresponding parts in the different figures.
DETAILED DESCRIPTION
[0072] The feeder shown herein is similar in construction to that shown in U.S. Pat. No. 6,923,142 of the present inventor, the disclosure of which is incorporated herein by reference.
[0073] The feeder shown herein also uses an insert piece similar in construction to that shown in U.S. Pat. No. 5,967,083 of the present inventor, the disclosure of which is incorporated herein by reference.
[0074] A feeder is generally indicated at 10 and includes a hopper 11 and a trough 12 . The trough is connect to the hopper by end walls 13 so as to form an integral structure with generally open top 14 through which feed can be inserted for containing in the hopper and for discharge into the trough 12 for feeding by one or more animals. In the embodiment shown there is provided a shelf 15 with a generally horizontal surface 16 , an upturned edge 17 and a downwardly turned lip 18 all of which are substantially as described in the above patents of Kleinsasser. Further details of the structure therefore can be obtained by reference to the above patents so that no further detailed description is necessary herein. A water supply 19 into the trough can be provided under controlled operation or operation by the animal as is known in the above patents.
[0075] The shape and arrangement of the hopper and trough can be varied and can provide either a two sided structure as shown or a single sided structure.
[0076] The height of the shelf relative to the end wall of the hopper is adjusted by raising straps 20 where each strap is arranged at a respective end of the shelf and lies along the end wall 13 parallel to the end wall. The strap is raised and lowered by a lever 21 which can be connected to a support plate 22 by on either a first pivot pin 23 or a second pivot pin 23 A. The support plate 22 includes an upper mounting flange 24 which is attached to the end wall 13 . A bend portion 25 is arranged at right angles to the flange portion 24 and therefore supports the plate 22 at a spaced position from the wall 13 leaving a space behind the plate 22 and inside the end wall 13 . The plate 22 is formed from sheet metal which is bent and cut to form the required shape as defined above so that the plate is suspended along the end wall with a bottom edge 27 and at two side edges 28 and 29 .
[0077] The first pivot pin 23 is arranged adjacent the side edge 29 of the plate and the second pivot pin 23 A is arranged adjacent the side edge 28 of the plate. The lever 21 is also formed of sheet metal which is stamped and punched to form a generally elongate member with an end 30 at the pivot pin 23 and a second end 31 extended beyond the edge 29 of the plate. The lever is formed of flat sheet metal similar to that of the plate so that it lies in contact with the front face of the plate. The lever 21 is attached to the strap 20 by a pin 32 which passes through a hole in the lever and a hole in the strap. A slot 35 is provided in the plate 22 which guides movement of the pin 32 so that the pin is constrained to move vertically and thus move the strap 20 vertically. The length of the slot 35 between an upper end 36 and a lower end 37 provides a length of adjustment equal the allowable movement of the lever 21 . A slot 38 in the lever allows the pin to move in the vertical direction while accommodating the arcuate movement of the lever.
[0078] The plate defines a first graduated scale 39 A on the edge 29 cooperating with the lever when the lever 21 is pivotally mounted on the pin 23 and a second graduated scale 39 B on the edge 28 cooperating with the lever 21 when the lever is pivotally mounted on the pin 23 A.
[0079] The graduated scale 39 A on the edge 29 of the plate 22 faces away from the pivot axis of the pivot pin 23 and is cut to form a series of saw teeth 39 along the edge 29 from an upper edge 40 to a lower edge 41 . Thus the edge 29 of the plate 22 forms an arcuate edge around the axis of the pin 23 A with the saw teeth punched in the edge of the plate and facing away from the plate as a serrated edge.
[0080] In a symmetrical manner, the graduated scale 39 B on the edge 28 of the plate 22 faces away from the pivot axis of the pivot pin 23 A and is cut to form a series of saw teeth 39 along the edge 29 from an upper edge 40 to a lower edge 41 . Thus the edge 28 of the plate 22 forms an arcuate edge around the axis of the pin 23 A with the saw teeth punched in the edge of the plate and facing away from the plate as a serrated edge.
[0081] The lever 21 is held flat against the surface of the plate 22 by a spring 43 on the pin 32 . The spring is held in place by a nut 44 on the pin 32 so that the spring is compressed between the nut and the outer face 45 of the lever 21 . The pin 32 has a head 46 behind the strap 20 . The pivot pin 23 provides enough flexibility to allow the lever 21 to be moved away from the plate 22 compressing the spring 43 against the bias of the spring 43 . The lever 21 has a hole 48 formed in the lever. The lever further has a recessed portion 49 which is bent downwardly from the plane of the lever into the plane of the plate 22 . Thus the recessed portion 49 is bent downwardly and is then bent to lie in the common plane with the plate 22 . The portion 49 carries exposed teeth 55 at the inwardly facing edge of the recess portion 49 . Thus the lever is in its normal position flat against the surface of the plate 22 thus causing the saw teeth 55 of the edge of the lever to be in meshing engagement with the saw teeth 39 of the arcuate edge of the plate. The width of the saw teeth is equal on both surfaces so that the teeth are directly meshing. The number of teeth on the edge of the lever is very much less than the number of teeth on the arcuate edge of the plate since the lever is intended to move around the arcuate edge of the plate in an adjustment movement. However the amount of adjustment is equal the pitch of the saw teeth.
[0082] The lever 21 includes an end piece 58 which is bent in a direction away from the plate 22 so as to provide a handle or tab which can be readily grasped since it is sufficiently spaced from the end wall of the feeder to be readily accessible by the hand of the user.
[0083] Markings 59 are provided on the plate counting the number of saw teeth and numbered from zero at one end through to the total number at the other end of the arcuate edge of the plate. The hole 48 allows viewing of the markings through the hole onto the front surface of the plate so that the user can line up a centre line of the hole with a selected one of the markings.
[0084] In operation the meshing saw teeth arrangement of the lever and the plate allow a fine adjustment, bearing in mind that the saw teeth have a relatively fine pitch and bearing in mind that the distance of the pin 32 from the axis of the pivot pin 23 or 23 A is significantly less than the distance of the saw teeth from the pivot axis. Thus movement of one pitch of one saw tooth can be arranged to provide a movement of the shelf of a distance of the order of 1/32 to 1/16 inch.
[0085] The lever can be moved from a pivotal movement on the pin 23 to a pivotal movement on the pin 23 A by lifting the rear end 60 of the lever away from the plate against the action of the spring 43 and by dropping the rear end onto the selected one of the two pins. It will be appreciated that the changing of the pivot location acts to move the lever and the strap carried thereby downwardly by a distance equal to the vertical distance between the two pins thus providing a course adjustment movement of the shelf between the lowered position for younger or //weanling pigs and a raised position for the pigs after they have grown to a larger size. In each position the lever co-operates with the associated one of the graduated scales for fine adjustment.
[0086] In one arrangement (not shown), the bottom edge of the hopper is adjusted by an insert piece similar in construction to that shown in FIG. 7 of U.S. Pat. No. 5,967,083 of the present inventor with only difference that this is divided into separate pieces at longitudinally spaced positions so that the pieces can be inserted into place in the hopper despite the presence of the straps and the levers and the support plates at each end wall of the hopper. The number of pieces can be two or can be more in longer feeders.
[0087] In another arrangement shown in FIGS. 5 and 6 , the hopper includes a lower pivotal flap member 60 extending along the hopper between the end walls 13 . The flap member is in the form of a flat plate with a top edge 61 and a bottom edge 62 . The flap member is mounted at each end on the respective end wall 13 . The flap member is mounted on a pair of pivot levers 63 and 64 each pivotally connected at one end to a rear flange 65 of the flap member and at the other end to the end wall 13 of the feeder at a respective pivot pin 66 , 67 . Thus the flap member is arranged to move from a raised position shown in FIG. 5 to a lowered position shown in FIG. 6 .
[0088] In the raised position of the flap member the hopper itself has a bottom edge 70 which co-operates with the shelf in the raised position of the shelf. In this position, the pivotal flap member moves into its raised position exposing the bottom edge 70 where the flap member is out of the way along the outside of the hopper. In the lowered position, the flap member extends vertically downwardly from the bottom edge 70 so that the bottom edge 62 of the flap member in effect operates as the bottom edge of the hopper and the flap member acts as an extension of the bottom of the hopper. Although only one flap member is shown for convenience, there are two parallel cooperating flap members one on each side of the bottom edges 70 and defining in effect an extension of the parallel lower neck of the hopper. The flap member is arranged to co-operate with the hopper so as to provide a seal between the bottom edge 70 and the top edge of the flap member to prevent the escape of the feed material. At the ends the flap member is sufficiently close to the end walls 13 to prevent the escape of material. A suitable locking arrangement (not shown) is provided to hold the flap member in its raised and lowered position to prevent the pigs from activating movement of the flap member to cause damage or inadvertent release of feed material.
[0089] Since various modifications can be made in my invention as herein above described, and many apparently widely different embodiments of same made within the spirit and scope of the claims without department from such spirit and scope, it is intended that all matter contained in the accompanying specification shall be interpreted as illustrative only and not in a limiting sense. | An animal feeder includes a hopper above a shelf onto which feed can fall to be taken by the animal or dropped into a trough below the shelf. The height of the shelf is adjustable in a course movement to move the shelf from a low height for smaller animals to a raised height for the animal after they have grown. The shelf is also adjustable in fine movement to change the width of the opening through which the feed passes to control feed rate. The shelf is carried on straps which extend along the end walls of the hopper and are movable by an adjustment linkage defined by a plate carried on the end wall and a manually adjustable lever mounted for pivotal movement on the plate. The lever has two pivot positions on the plate providing the two course adjustments and two graduated scales for the fine adjustment each cooperating with a respective pivot position. | 0 |
TECHNICAL FIELD
[0001] This disclosure relates to an electrified vehicle, and more particularly, but not exclusively, to a vehicle system and method for closing a contactor prior to starting the vehicle.
BACKGROUND
[0002] Generally, electrified vehicles differ from conventional motor vehicles in that they are selectively driven using one or more battery powered electric machines. Conventional motor vehicles, by contrast, rely exclusively on an internal combustion engine to drive the vehicle. Electrified vehicles may use electric machines instead of, or in addition to, internal combustion engines. The electric machines are typically powered by high voltage batteries.
[0003] Electrified vehicles may utilize one or more contactors that isolate energy stored in the high voltage batteries from other vehicle loads. For example, the contactors may act as high voltage relays for switching supply voltages to other high voltage components on the vehicle (e.g., electric machines, A/C compressor, PTC heater, DCDC converter, etc.). The contactors connect the battery to a high voltage bus during normal vehicle operation in order to power the electric machine(s).
SUMMARY
[0004] A method according to an exemplary aspect of the present disclosure includes, among other things, controlling an electrified vehicle by closing a contactor prior to a key on condition of the electrified vehicle.
[0005] In a further non-limiting embodiment of the foregoing method, the controlling step includes closing the contactor in response to an early wake trigger.
[0006] In a further non-limiting embodiment of either of the foregoing methods, the early wake trigger includes applying a brake of the electrified vehicle.
[0007] In a further non-limiting embodiment of any of the foregoing methods, the early wake trigger includes positioning a key in an ignition of the electrified vehicle.
[0008] In a further non-limiting embodiment of any of the foregoing methods, the early wake trigger includes at least one of unlocking a door of the electrified vehicle, sitting in a seat of the electrified vehicle, detecting a key in proximity to the electrified vehicle, and opening a door of the electrified vehicle.
[0009] A method according to another exemplary aspect of the present disclosure includes, among other things, closing a contactor in response to an early wake trigger to reduce a vehicle start time associated with an electrified vehicle.
[0010] In a further non-limiting embodiment of the foregoing method, the early wake trigger occurs prior to a key on condition of the electrified vehicle.
[0011] In a further non-limiting embodiment of either of the foregoing methods, the early wake trigger includes applying a brake of the electrified vehicle.
[0012] In a further non-limiting embodiment of any of the foregoing methods, the early wake trigger includes positioning a key in an ignition of the electrified vehicle.
[0013] In a further non-limiting embodiment of any of the foregoing methods, the closing step occurs prior to a key on condition of the electrified vehicle.
[0014] In a further non-limiting embodiment of any of the foregoing methods, the method includes awakening various systems of the electrified vehicle prior to the closing step.
[0015] In a further non-limiting embodiment of any of the foregoing methods, the method includes communicating a wake-up signal from a first control unit to a second control unit, communicating a command signal from the second control unit to a third control unit and commanding the closing step with the third control unit in response to receiving the command signal.
[0016] In a further non-limiting embodiment of any of the foregoing methods, the first control unit is a body control module, the second control unit is a hybrid powertrain control module, and the third control unit is a battery electronic control module.
[0017] In a further non-limiting embodiment of any of the foregoing methods, the wake-up signal is communicated in response to sensing the early wake trigger.
[0018] In a further non-limiting embodiment of any of the foregoing methods, the method includes opening the contactor if a start request is not received after a threshold amount of time has passed.
[0019] A vehicle system according to another exemplary aspect of the present disclosure includes, among other things, a contactor and a control unit configured to close the contactor in response to an early wake trigger.
[0020] In a further non-limiting embodiment of the foregoing vehicle system, the contactor is commanded closed to connect a battery to an electric machine over a high voltage bus.
[0021] In a further non-limiting embodiment of either of the foregoing vehicle systems, at least one sensor is configured to detect the early wake trigger.
[0022] In a further non-limiting embodiment of any of the foregoing vehicle systems, the system includes a second control unit and a third control unit, the second control unit configured to communicate a wake-up signal to the third control unit in response to the early wake trigger.
[0023] In a further non-limiting embodiment of any of the foregoing vehicle systems, the third control unit is configured to communicate a command signal for closing the contactor to the control unit in response to receiving the wake-up signal.
[0024] The embodiments, examples and alternatives of the preceding paragraphs, the claims, or the following description and drawings, including any of their various aspects or respective individual features, may be taken independently or in any combination. Features described in connection with one embodiment are applicable to all embodiments, unless such features are incompatible.
[0025] The various features and advantages of this disclosure will become apparent to those skilled in the art from the following detailed description. The drawings that accompany the detailed description can be briefly described as follows.
BRIEF DESCRIPTION OF THE DRAWINGS
[0026] FIG. 1 schematically illustrates a powertrain of an electrified vehicle.
[0027] FIG. 2 illustrates a vehicle system of an electrified vehicle.
[0028] FIG. 3 schematically illustrates an exemplary start-up sequence of an electrified vehicle.
[0029] FIG. 4 illustrates a vehicle system according to another embodiment of this disclosure.
DETAILED DESCRIPTION
[0030] This disclosure relates to a vehicle system that closes a contactor in response to an early wake trigger to reduce electrified vehicle start times. For example, the contactor may be closed prior to starting the electrified vehicle in response to sensing that a driver has applied the vehicle brakes, positioned a key in an ignition of the vehicle, or in response to any other early wake trigger. Closing the contactors at early wake reduces the amount of time necessary to ready the vehicle to drive.
[0031] FIG. 1 schematically illustrates a powertrain 10 of an electrified vehicle 12 . Although depicted as a hybrid electric vehicle (HEV), it should be understood that the concepts described herein are not limited to HEV's and could extend to other electrified vehicles, including, but not limited to, plug-in hybrid electric vehicles (PHEV's), battery electric vehicles (BEV's), and modular hybrid transmission vehicles.
[0032] In one embodiment, the powertrain 10 is a powersplit powertrain system that employs a first drive system and a second drive system. The first drive system includes a combination of an engine 14 and a generator 18 (i.e., a first electric machine). The second drive system includes at least a motor 22 (i.e., a second electric machine), the generator 18 , and a battery 24 . In this embodiment, the second drive system is considered an electric drive system of the powertrain 10 . The first and second drive systems generate torque to drive one or more sets of vehicle drive wheels 28 of the electrified vehicle 12 .
[0033] The engine 14 , which is an internal combustion engine in this embodiment, and the generator 18 may be connected through a power transfer unit 30 , such as a planetary gear set. Of course, other types of power transfer units, including other gear sets and transmissions, may be used to connect the engine 14 to the generator 18 . In one non-limiting embodiment, the power transfer unit 30 is a planetary gear set that includes a ring gear 32 , a sun gear 34 , and a carrier assembly 36 .
[0034] The generator 18 can be driven by the engine 14 through the power transfer unit 30 to convert kinetic energy to electrical energy. The generator 18 can alternatively function as a motor to convert electrical energy into kinetic energy, thereby outputting torque to a shaft 38 connected to the power transfer unit 30 . Because the generator 18 is operatively connected to the engine 14 , the speed of the engine 14 can be controlled by the generator 18 .
[0035] The ring gear 32 of the power transfer unit 30 may be connected to a shaft 40 , which is connected to vehicle drive wheels 28 through a second power transfer unit 44 . The second power transfer unit 44 may include a gear set having a plurality of gears 46 . Other power transfer units may also be suitable. The gears 46 transfer torque from the engine 14 to a differential 48 to ultimately provide traction to the vehicle drive wheels 28 . The differential 48 may include a plurality of gears that enable the transfer of torque to the vehicle drive wheels 28 . In one embodiment, the second power transfer unit 44 is mechanically coupled to an axle 50 through the differential 48 to distribute torque to the vehicle drive wheels 28 .
[0036] The motor 22 (i.e., the second electric machine) can also be employed to drive the vehicle drive wheels 28 by outputting torque to a shaft 52 that is connected to the second power transfer unit 44 . In one embodiment, the motor 22 and the generator 18 cooperate as part of a regenerative braking system in which both the motor 22 and the generator 18 can be employed as motors to output torque. For example, the motor 22 and the generator 18 can each output electrical power to the battery 24 .
[0037] The battery 24 is one exemplary type of an electrified vehicle battery assembly and may take the form of a high voltage battery that is capable of outputting electrical power to operate the motor 22 and/or the generator 18 . Other types of energy storage devices and/or output devices can also be used to supply power within the electrified vehicle 12 .
[0038] The powertrain 10 may additionally include a control system 58 for monitoring and/or controlling various aspects of the electrified vehicle 12 . For example, the control system 58 may communicate with the electric drive system, the power transfer units 30 , 44 or other components to monitor and/or control the electrified vehicle 12 . The control system 58 includes electronics and/or software to perform the necessary control functions for operating the electrified vehicle 12 . In one non-limiting embodiment, the control system 58 is a combination vehicle system controller and powertrain control module (VSC/PCM). Although it is shown as a single hardware device, the control system 58 may include multiple controllers in the form of multiple hardware devices, or multiple software controllers within one or more hardware devices.
[0039] A controller area network (CAN) 60 allows the control system 58 to communicate with the powertrain 10 . For example, the control system 58 may receive signals from the powertrain 10 to indicate whether a transition between shift positions is occurring. The control system 58 may also communicate with a battery control module of the battery 24 , or other control devices.
[0040] The powertrain 10 may additionally include one or more contactors 56 as part of a contactor assembly that acts as a high voltage relay for switching supply currents that are communicated to the motor 22 and/or the generator 18 . The contactors 56 may be selectively moved between an open position and a closed position to disconnect/connect the battery 24 to the motor 22 and/or generator 18 , or other loads, over a high voltage bus 62 . The contactors 56 are typically closed during a drive cycle of the electrified vehicle 12 . Closing the contactors 56 permits electrical power to circulate to and from the battery 24 . At the conclusion of the drive cycle, when the powertrain 10 is not operating, the contactors 56 will be opened to disconnect the battery 24 from high voltage components.
[0041] In one non-limiting embodiment, the powertrain 10 may employ two contactors 56 , one of which is a pre-charge contactor. When commanded to close, the pre-charge contactor closes, then after a predefined charge is reached, the main contactor is closed and the pre-charge contactor opens during normal operation of the electrified vehicle 12 . In response to a vehicle key off condition, the contactors open to isolate the battery 24 from the high voltage bus 62 .
[0042] FIG. 2 illustrates a vehicle system 64 that may be incorporated into an electrified vehicle, such as the electrified vehicle 12 of FIG. 1 , in order to reduce start times of the electrified vehicle. The exemplary vehicle system 64 includes a contactor 56 that electrically connects and disconnects a battery 24 from an electric machine 66 . Although only a single contactor 56 is shown in FIG. 2 , the vehicle system 64 could incorporate any number of contactors within the scope of this disclosure. In one non-limiting embodiment, the vehicle system 64 may close the contractor 56 when the electrified vehicle is off in order to improve vehicle start times.
[0043] The vehicle system 64 may additionally include a sensor 68 and a control unit 70 . The sensor 68 is adapted to sense an early wake trigger 72 . For example, in one non-limiting embodiment, the sensor 68 may sense whether the vehicle operator or driver has applied a brake of the electrified vehicle. In another embodiment, the sensor 68 may detect whether a key has been positioned in an ignition of the electrified vehicle. Additional non-limiting examples of early wake triggers that can be monitored and detected by the sensor 68 include whether a vehicle door has been opened, whether a vehicle key is in relative proximity to the electrified vehicle, whether the electrified vehicle has been unlocked, whether a passenger has seated themselves in a seat of the vehicle, or any other early wake trigger. Generally, the early wake trigger 72 instructs the vehicle system 64 that a driver intends to start the electrified vehicle. Stated another way, the early wake trigger 72 occurs prior to starting the electrified vehicle or while the vehicle is in a key off condition.
[0044] The control unit 70 may be part of a vehicle control system, such as the control system 58 of FIG. 1 , or could alternatively be a stand-alone control unit. In one embodiment, the control unit 70 is adapted to close the contactor 56 in response to the early wake trigger 72 . For example, the sensor 68 may communicate an early wake signal 74 to the control unit 70 when the early wake trigger 72 is sensed. The control unit 70 may then communicate a command signal 51 to the contactor 56 that instructs the contactor 56 to close, such as by closing a relay switch or moving a movable contact into position relative to a stationary contact, thereby allowing high voltage current to flow over the high voltage bus 62 to power the electric machine 66 .
[0045] In another embodiment, the control unit 70 may communicate another command signal S 2 to open the contactor 56 if a start request has not been received after a threshold amount of time has passed since the early wake trigger 72 was sensed. For example, by way of one non-limiting embodiment, the control unit 70 may communicate the command signal S 2 to open the contactor 56 if one minute has passed since the early wake trigger 72 and a driver has not attempted to start the electrified vehicle.
[0046] FIG. 3 , with continued reference to FIG. 1 and FIG. 2 , schematically illustrates an exemplary startup sequence 99 of an electrified vehicle 12 that has been equipped with the vehicle system 64 . The exemplary startup sequence 99 may be performed to reduce the start times associated with the electrified vehicle 12 .
[0047] The startup sequence 99 may begin in response to sensing an early wake trigger 72 at a time T 0 . Shortly thereafter, after various vehicle startup procedures and sequences have been initiated and performed, the control unit 70 may command the contactor 56 closed (closing indicated by a triangle in FIG. 3 ) at a time T 1 . The time T 1 occurs before a vehicle start request 80 has been made. The vehicle start request 80 may occur at a time T 2 .
[0048] The electrified vehicle 12 is considered ready to drive 82 at a time T 3 . The time T 3 can occur relatively soon after the vehicle start request 80 has been made by closing the contactor 56 at a period of time prior to starting the electrified vehicle 12 (i.e., at time T 1 ). In one non-limiting embodiment, as little as 66 milliseconds may pass between the times T 2 and T 3 . This is a relatively short amount of time compared to prior art vehicle systems which can require over 400 milliseconds between the times T 2 and T 3 to ready the electrified vehicle 12 for drive.
[0049] FIG. 4 illustrates another exemplary vehicle system 164 . In this disclosure, like reference numbers designate like elements where appropriate and reference numerals with the addition of 100 or multiples thereof designate modified elements that are understood to incorporate the same features and benefits of the corresponding original elements.
[0050] In this embodiment, the vehicle system 164 includes at least one contactor 156 that selectively connects and disconnects a battery 124 from an electric machine 166 . In one non-limiting embodiment, the vehicle system 164 may close the contractor 156 when the electrified vehicle is off in order to improve vehicle start times.
[0051] A sensor 168 is adapted to sense an early wake trigger 172 . Generally, the early wake trigger 172 instructs the vehicle system 164 that a driver intends to start the electrified vehicle. The early wake trigger 172 occurs prior to starting the electrified vehicle or while the vehicle is in a key off condition.
[0052] The vehicle system 164 of this embodiment includes a first control unit 170 - 1 , a second control unit 170 - 2 , and a third control unit 170 - 3 . In one non-limiting embodiment, the first control unit 170 - 1 is a body control module of the electrified vehicle, the second control unit 170 - 2 is a powertrain control module and the third control unit 170 - 3 is a battery electronic control module. Of course, the vehicle system 164 could include other controller arrangements.
[0053] In one non-limiting control method, the sensor 168 may communicate an early wake signal 174 to the first control unit 170 - 1 upon sensing the early wake trigger 172 . The first control unit 170 - 1 may then communicate a wake-up signal S 1 to the second control unit 170 - 2 . Once awake, the second control unit 170 - 2 can communicate a command signal S 2 to the third control unit 170 - 3 . Once the third control unit 170 - 3 receives the command signal S 2 , it instructs the contactor 56 to close, via another command signal S 3 , to allow high voltage current to flow over a high voltage bus 162 to power the electric machine 166 or any other load.
[0054] Although the different non-limiting embodiments are illustrated as having specific components or steps, the embodiments of this disclosure are not limited to those particular combinations. It is possible to use some of the components or features from any of the non-limiting embodiments in combination with features or components from any of the other non-limiting embodiments.
[0055] It should be understood that like reference numerals identify corresponding or similar elements throughout the several drawings. It should be understood that although a particular component arrangement is disclosed and illustrated in these exemplary embodiments, other arrangements could also benefit from the teachings of this disclosure.
[0056] The foregoing description shall be interpreted as illustrative and not in any limiting sense. A worker of ordinary skill in the art would understand that certain modifications could come within the scope of this disclosure. For these reasons, the following claims should be studied to determine the true scope and content of this disclosure. | A method according to an exemplary aspect of the present disclosure includes, among other things, controlling an electrified vehicle by closing a contactor prior to a key on condition of the electrified vehicle. | 1 |
This invention relates to a child's playseat. It relates more particularly to a child's cantilevered bouncer and walker of the foldable variety.
BACKGROUND OF THE INVENTION
Usually a cantilevered playseat includes a base which rests on the floor and a seat which is supported above the base by parallel inclined arms at each side of the base which are pivoted to the base and to the seat. The arms are spring biased so as to tend to maintain the seat in a generally horizontal orientation above the base. However, when a child exerts weight on the seat or bounces up and down in the seat, the arms pivot relative to the base and the seat in such a way as to permit the seat to swing up and down relative to the base while maintaining its horizontal orientation. Usually provision is also made for releasing the spring so that the arms and the seat can fold down against the base with the folded playseat forming a relatively compact package for efficient storage.
Conventional playseats of the cantilevered type have various drawbacks which militate against their wider use. Some are composed of a relatively large number of parts and linkages. Others have pinch points which could cause injury to a child playing in the seat. In some cantilevered bouncers and walkers the folding mechanism can be released accidentally by a child sitting in the playseat causing collapse of the seat which could cause injury to the child. Finally, most foldable cantilevered seats resiliently bias the seat above the base by extensible coil springs. If the springs should break or their connections to the playseat frame should part, the seat supporting the child collapses to the floor, again with possible injurious consequences. Examples of such prior playseats of this general type are described in U.S. Pat. Nos. 2,927,628, 2,976,911, 3,007,667, 3,054,591, 3,061,261, 3,076,628, and 3,096,963.
SUMMARY OF THE INVENTION
Accordingly, the present invention aims to provide an improved foldable walker and bouncer of the cantilevered type.
Another object is to provide a playseat of this general type which folds easily into a relatively compact package.
A further object of the invention is to provide a cantilevered playseat which has no pinch points which are accessible to a child sitting in the seat.
A further object of the invention is to provide a cantilevered playseat which is composed of relatively few parts and linkages.
Yet another object of the invention is to provide a resilient cantilevered playseat which does not drop the occupant to the floor when its springs fail.
Still another object of the invention is to provide a cantilevered playseat which is relatively economical to manufacture.
Other objects will, in part, be obvious and will, in part, appear hereinafter.
The invention accordingly comprises the principles of construction, combination of elements and arrangement of parts which will be exemplified in the following detailed description, and the scope of the invention will be indicated in the claims.
Briefly, my playseat comprises a horizontal, generally U-shaped base provided with casters which are arranged to roll on the floor or ground. The ends of the legs of the base are turned upwards. A generally U-shaped seat-supporting frame member is juxtaposed with the base frame member, the ends of its legs being pivotally connected to the upturned ends of that base frame member. Pivotally connected to each leg of the seat-supporting frame member is one end of a telescoping strut whose opposite end is pivotally connected to the bight of a bail whose opposite ends are, in turn, pivotally connected to the base. Normally the bail is maintained in an overcenter position on the base so that it supports the struts in more or less upstanding positions. Also, each strut is spring-loaded toward its extended position so that the struts together maintain the seat-supporting frame member in an inclined elevated orientation above the base frame member. A generally U-shaped back frame member has the opposite ends of its legs pivotally connected to the legs of the seat-supporting member at more or less the same location as the pivotal connections of that latter member to the struts. Means are provided for selectively locking the back frame member at selective angular positions relative to the seat-supporting member so the occupant of the playseat can be supported in an upright or reclined position. A conventional bag seat is suspended from the back frame member and the seat-supporting member for supporting a child and, if desired, a tray may be supported at the forward end of the seat-supporting frame member to contain articles for amusing the occupant of the playseat.
When the playseat is in its erect position as aforesaid, the seat-supporting frame member and the bag seat and the occupant thereof are resiliently supported above the base. Therefore, the occupant of the seat by placing his feet on the floor below the base can bounce the seat up and down or walk the playseat along the floor with his feet. Since the seat is supported in its erect position by compression spring-loaded telescoping struts, there is no possibility of the springs breaking and causing the seat to collapse to the floor. Even if the compression springs in the struts should be completely compressed, the seat and its occupant are still positioned a considerable distance above the base.
As will be described in detail later, special protective covers are provided at the pivotal connections between the struts and the base frame member and the back frame member so that there are no pinch points within reach of the occupant of the playseat that could cause injury to the his fingers.
The seat is folded to its collapsed position by swinging the bail supporting the lower ends of the struts about its pivots to the base. This shifts the lower ends of the struts forwardly by a sufficient amount to permit the seat-supporting frame member to swing down against the base. Such folding cannot occur when the seat is occupied because the weight of the occupant exerted through the struts prevents the bail from being swung from its normal overcenter position. Also as an added safety measure a latch, inaccessible to the child, is provided to positively lock the bail in its normal position. The back frame member can be manipulated so that it can be swung about its pivots to the seat supporting member down against the base so that the folded playseat as a whole occupies a relatively small amount of space.
Thus my playseat which functions both as a bouncer and as a walker is composed of a relatively few formed metal parts so that it is relatively easy and inexpensive to manufacture. The playseat is also a relatively safe item of juvenile furniture in that there is no possibility of the seat collapsing in the event of the breakage of a spring. Moreover, there is little likelihood of the occupant of the seat being able to manipulate the folding mechanism so as to permit the seat to collapse when the child is in the seat. Accordingly, it should prove to be a successful item of juvenile furniture.
BRIEF DESCRIPTION OF THE DRAWING
For a fuller understanding of the nature and objects of the invention, reference should be had to the following detailed description taken in connection with the accompanying drawing, in which:
FIG. 1 is a perspective view of a playseat made in accordance with this invention;
FIG. 2 is a side elevational view on a larger scale showing the playseat as erected in greater detail;
FIG. 3 is a similar view showing the playseat in its partially folded condition;
FIG. 4 is a similar view showing the playseat fully folded;
FIG. 5 is a side elevational view on a larger scale with parts broken away showing the pivot assembly portion of the FIG. 1 playseat in greater detail;
FIG. 6 is a sectional view along line 6--6 of FIG. 5;
FIG. 7 is a view similar to FIG. 5 showing the opposite side of that assembly;
FIG. 8 is a sectional view along line 8--8 of FIG. 5, and
FIG. 9 is an exploded view showing the various pivot assembly parts.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to FIGS. 1 to 3 of the drawing, my playseat is supported above the floor or ground by a generally U-shaped base frame member shown generally at 10 having a pair of legs 10a connected by an upturned bight 10b. The leg ends 10c are also turned upwards. Conventional casters 12 are pivotally connected near the opposite ends of the legs 10a so that the base frame member can be rolled along the ground. A generally U-shaped seat-supporting frame member indicated generally at 14 has opposite side legs 14a connected by a bight 14b. The end 14c of each leg is connected by pivots 16 to the upturned end 10c of the base frame member.
The seat-supporting frame member 14 is supported at an inclined elevated position above the base frame member 10 by a pair of telescoping struts shown generally at 18. Each strut includes an upper section 18a and a lower section 18b which are urged toward their extended position by a coiled compression spring 22 (FIG. 2) inside section 18b. The upper end of the strut section 18a is connected by a special pivot shown generally at 24 to be described in detail later to a frame member leg 14a about a third of the way along that leg from its end 14c. The lower end of each strut section 18b is pivotally connected to a generally U-shaped bail shown generally at 28 which is, in turn, pivotally connected to the legs 10a of the base frame member 10.
More particularly, the lower ends of the strut sections 18b are provided with lateral openings 32 (FIG. 3) which rotatively receive the bight 28a of the bail 28 near opposite ends of the bail just inboard of the base frame member legs 10a. The legs 28b of the bail, on the other hand, are bent forwardly generally parallel to the legs 10a and their ends 28c are connected by pivots 34 to the legs 10a. Thus when the seat is in its erect position shown in FIGS. 1 and 2, the opposite ends of the bail bight 28a extend across and engage the base frame member legs 10a so as to maintain the bail in an overcentered position rotatively supporting the lower ends of the struts more or less even with the plane of the base frame member. Preferably also, the mid-portion 28d of the bail bight inboard of the struts 18 is bent upwardly as best seen in FIG. 1 so as to prevent the lower ends of the struts from toeing in toward the center of the playseat.
The playseat also includes a generally U-shaped back frame member indicated generally at 42 having a pair of parallel arms 42a connected at their tops by a bight 42b. The lower ends 42c of the legs are adjustably pivotally connected to the pivots 24 in a manner to be described later permitting the back frame member to assume various orientations relative to the seat frame member so as to support the occupant of the playseat in different positions.
A standard bag seat S is removably secured to the seat-supporting frame member 14. To facilitate this, the foward ends of the legs 14a are bent so that they are oriented generally parallel to the base frame member legs 10a when the seat is in its erect position illustrated in FIGS. 1 and 2. The seat S also includes a back portion S' which removably engages over the top of the back frame member 42 so that the seat S completely supports an infant or small child sitting in the seat. Also a standard tray T can be removably secured at the forward end of the seat-supporting frame member 14 to contain toys for the child using the seat.
It is a feature of my playseat that there are no weak linkages whose parting could cause the seat to collapse. More particularly and still referring to FIG. 2, the bottom ends of struts 18 are positively supported by the bail 28 which positively engages the tops of the base frame member legs 10a just adjacent the strut ends. The upper ends of the struts are located directly under the pivots 24 which can function as positive stops for the struts. Resultantly, even if a considerable downward force is applied by the child to the playseat, substantially all of that load is directly downward and is reflected in compression of the struts 18 rather than any extension or bending of a link. Therefore the playseat is very strong and safe.
It should be noted also that when the playseat is occupied, the weight of the occupant pushes the struts 18 downward so that the over center bail 28 is urged even more firmly against the base frame member legs 10a. Also most preferably, one or more spring-loaded latches are provided to lock the bail bight 28a positively against the base frame member. One such latch is illustrated generally at 46 in FIG. 1. It comprises a pair of depending legs 46a which straddle the base frame member leg 10a. Those legs are connected by a pivot 48 to the leg and the latch includes a nose 48b which engages over the bail bight 28a. A spring (not shown) biases the latch toward that engaging position. Thus in order to move the bail, the latch 46 first has to be retracted from the bail.
The seat is folded for storage by depressing latch 46 so as to disengage it from the bail and then swinging the bail 28 forwardly about its pivot 34 through the position shown in FIG. 3. This motion moves the lower ends of the struts 18 forward sufficiently to permit the seat-supporting frame member 14 to swing down against the base frame member 10 as shown in FIG. 4. Then the back frame member 42 can be releasably swung forwardly so that it lies substantially flush against the top of seat-supporting frame member 14 as seen in that same figure. Consequently, the folded playseat forms a very compact package.
Referring now to FIGS. 5 to 9, each pivot 24 includes a relatively heavy round metal disk 62 which engages against the inside of a seat-supporting frame member leg 14a. The disk has a laterally extending lug 62a which projects through an opening 64 in that leg. Also the disk has a tongue 62b which extends downward when the playseat is in its erect position as shown in FIGS. 1 and 2. This tongue is connected by a pivot 65 to the upper end of the strut section 18a. A cup-shaped decorative plastic cap 68 is engaged over the frame member leg 14a, suitable openings 72 being provided at diametrically opposite points at the sides of the cap 68 to accommodate the leg.
A screw 74 extends through a central opening 76 in cap 68 and through aligned openings 78 in the walls of leg 14a and thence through a central opening 82 in disk 62. Inboard of disk 62 is a circular plastic disk 84 having a central opening 86 which also receives screw 74. The cap 68 is shaped and arranged so that its rim is more or less flush with the plastic disk 84 so that the plastic disk and cap completely enclose the metal disk 62. After passing through disk 84, the screw 74 extends through a centrally located slot 88 in the flattened end 42c of the back frame member leg 42a. A sleeve 90 and a washer 91 best seen in FIG. 9 are slid onto the screw at legend 42c. Finally, all of the aforesaid components are clamped together by a nut 92 turned down onto the end of the screw 74.
A lug 94 projects laterally from each leg end 42c through a slot 96 in the plastic disk 84 and into an arcuate slot 98 in disk 62. Thus when the back frame member 42 is swung about its pivot screws 74, the lugs 94 on its legs ride in the corresponding slots 98. A pair of notches 98a and 98b are formed in the lower edge of slot 98. The slots 88 in the frame member ends 42c permit those ends to move vertically so that when the lugs 94 are aligned with one or another of the notches 98a, 98b, the lugs engage in the notches to lock the back frame member in place. Those notches are positioned so that such engagements occur when the back frame member is more or less upright and when the back rest member is in a more reclined position. Of course, additional notches may be provided to set a variety of different inclinations of the back frame member to support the playseat occupant in different reclining positions.
It will be seen from the foregoing, then, that the playseat made in accordance with this invention is composed of a relatively few parts so that it is relatively inexpensive to manufacture. When the seat is in its erect position, a child in the seat can bounce up and down and walk about without any likelihood of the playseat collapsing due to breakage of the seat biasing means or other linkages. Finally, a child in the playseat is protected by caps 68 from potential pinch points and due to the mode of folding the seat and the presence of latches 46, there is little likelihood of the child being able to release the seat so that it folds while he is in it.
It will thus be seen that the objects set forth above, among those made apparent from the preceding description, are efficiently attained and, since certain changes may be made in the above construction without departing from the scope of the invention, it is intended that all matter contained in the above description or shown in the accompanying drawing be illustrative and not in a limiting sense.
It is also to be understood that the following claims are intended to cover all of the generic and specific features of the invention herein described. | A foldable cantilevered playseat has a base and a generally U-shaped seat-supporting member whose ends are pivotally connected to the base. Telescoping resiliently biased struts pivotally connected between the frame member legs and the bight of a bail swingably connected to the base resiliently bias the seat-supporting frame member above the base. A fabric seat supported by the frame member is arranged to support a child so that his feet can engage the floor below the base. | 0 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a constant-speed running control device which stores a given speed of a vehicle and maintains the vehicle automatically at the stored car speed and, more particularly, to the constant-speed running control device which includes a low-temperature release means for releasing, in response to actuation of a temperature switch means being actuated when an ambient temperature lowers, the control of an actuator means for controlling open/close of a throttle valve.
2. Description of the Prior Art
One conventional constant-speed running control device operates in such a manner that its computer stores a given car speed, compares with the current car speed, and controls an actuator such that the difference between the two becomes zero, as a result, a constant-speed running control process is performed through open/close of a throttle valve attached to the actuator.
According to such a type as above of constant-speed running control device, however, if the surrounding temperature of a vehicle becomes abnormally low, the actuator means for controlling open/close of the throttle valve tends to effect defective operation owing to the hardening of a rubber member included in the actuator means, the freezing of a wire for coupling together the actuator means and the throttle valve, and the like.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a constant-speed running control device which releases the control of an actuator means when an ambient temperature lowers.
To achieve the foregoing object, the present invention provides a constant-speed running control device comprising car speed detecting means for detecting the current car speed of a vehicle, memory means for storing a given car speed, an actuator for controlling a throttle valve, setting means for causing the memory means to store the given car speed, releasing means for releasing the control of the actuator, electronic control means for controlling the actuator in such a direction as to cause the difference between the stored car speed held in the memory means and the current car speed detected by the car speed detecting means to disappear, temperature detecting means, and low-temperature release means for actuating the release means in response to the output of the temperature detecting means.
According to the foregoing configuration, when the ambient temperature lowers below a predetermined temperature the temperature detecting means is actuated and this actuation is transmitted to the low-temperature release means. The low-temperature release means releases the control of the actuator to thereby inhibit a constant-speed running control process. Thereby, defective operation and the like can be prevented beforehand from occurring that would otherwise occur when the ambient temperature lowers abnormally.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a block diagram showing an embodiment of the present invention; and
FIG. 2 is a flowchart showing the operation of an electronic control unit.
DESCRIPTION OF THE PREFERRED EMBODIMENT
An embodiment of the present invention will now be described with reference to the drawings. FIG. 1 shows an example of an electric circuit of a constant-speed running control device according to the present invention.
In FIG. 1, the power of the circuit is supplied from a car battery BT through an ignition switch IGS and a fuse FS1 to a voltage stabilizer circuit 14. This voltage stabilizer circuit 14 generates a stable voltage of 5 volts from the power thus supplied and applies the generated voltage to an electronic control unit 10 and an interface circuit 12.
In the embodiment, the electronic control unit 10 is realized by a micro computer.
A switch SW1 is a stop switch responsive to manipulation of a brake pedal, a switch SW2 is a clutch switch responsive to manipulation of a clutch pedal, and as either of these two switches is actuated, a constant-speed running control process is released or cancelled,
A switch SW3 is a setting switch for constant-speed running, that is, as this setting switch SW3 is manipulated, a given car speed is stored and the constant-speed running control process is commenced.
A switch SW4 is a resume switch for constant-speed running, that is, as this resume switch SW4 is manipulated, the constant-speed running control process is commenced at the car speed stored before the beginning of the constant-speed running control process.
A switch SW5 is an acceleration switch for increasing the stored car speed being used at the time of constant-speed running, that is, the stored car speed is increased in response to manipulation of this acceleration switch SW5, the value thus increased is stored when the acceleration switch SW5 is returned, and then the constant-speed running control process is commenced.
A switch SW6 is a temperature switch being actuated when the ambient temperature lowers, that is, as this temperature switch SW6 is actuated, the constant-speed running control process is released.
Although several locations can be adopted as the spot where the temperature switch SW6 is attached, it is preferably provided in the vicinity of an actuator 100.
A switch SW7 is a reed switch for detection of the car speed, hence, a permanent magnet connected to a speed meter cable is disposed in the vicinity of this car speed detecting reed switch SW7.
One end of the stop switch SW1 is connected through a fuse FS2 to the ignition switch IGS with the other end grounded through a stop lamp LP. Both ends of the stop switch SW1 are connected through the interface circuit 12 to input ports P1 and P2 of the electronic control unit 10.
One end of the clutch switch SW2 is connected through the interface circuit 12 to an input port P3 of the electronic control unit with the other end grounded.
One end of the setting switch SW3 is connected through the interface circuit 12 to an input port P4 of the electronic control unit with the other end grounded.
One end of the resume switch SW4 is connected through the interface circuit 12 to an input port P5 of the electronic control unit with the other end grounded.
One end of the acceleration switch SW5 is connected through the interface circuit 12 to an input port P6 of the electronic control unit with the other end grounded.
One end of the temperature switch SW6 is connected through the interface circuit 12 to an input port P7 of the electronic control unit with the other end grounded.
One end of the reed switch SW7 is connected through the interface circuit 12 to an input port P8 of the electronic control unit with the other end grounded.
Output ports P9 and P10 of the electronic control unit 10 are connected through solenoid drive circuits 20 to solenoids SL1 and SL2, respectively.
An output port P11 of the electronic control unit 10 is connected with an LED which is turned on when a lowtemperature release means is actuated.
The negative-pressure actuator 100 is configured as follows: A housing 101 is made up of two housing parts 101a and 101b. A diaphragm 102 is pinched between flange portions of the housing parts 101a and 101b. A space surrounded by the diaphragm 102 and the housing part 101a defines a negative-pressure chamber, whereas another space surrounded by the diaphragm 102 and the housing part 101b is communicated with the atmosphere. Between the housing part 101a and the diaphragm 102 is interposed a compression coil spring 103 which pushes back the diaphragm 102 rightward as viewed in the drawing when the pressure inside the negative-pressure chamber becomes close to the atmospheric pressure. A lever 104 secured nearly to the center of the diaphragm 102 is coupled with the ring of a throttle valve 105. The housing part 101a is formed with a negative-pressure intake port 107 communicating with a negative-pressure source such as an intake manifold, and atmosphere intake ports 108 and 109.
Both a negative-pressure control valve 110 and a negative-pressure open valve 111 are provided in the housing part 101a. A movable segment 112 of the negative-pressure control valve 110 is tiltable whose one end is coupled with an extension coil spring 113 with the other end facing opposite the control solenoid SL1. Both ends of the movable segment 112 function as a valve member, and open/close the negative-pressure intake port 107 and close/open the atmosphere intake port 108 in response to energization/deenergization of the solenoid SL1.
Similarly to the negative-pressure control valve 110, the negative-pressure open valve 111 has a movable segment 114, an extension coil spring 115, and the solenoid SL2, but, this movable segment 114 closes/opens the atmosphere intake port 109.
At the time of constant-speed running control, the electronic control unit 10 compares the stored car speed with the current car speed and determines a duty ratio being used in controlling the control solenoids so as to make zero the difference between the two. If deceleration is necessary, the duty ratio is made small, that is, a time ratio at which the negative-pressure control valve 110 makes the inside of the negative-pressure actuator 100 communicate with the atmosphere is made large, as a result, the throttle valve is closed by the negative-pressure actuator 100. On the contrary, if acceleration is necessary, the duty ratio is made large, as a result, the throttle valve is opened by the actuator 100.
The operation of the micro computer serving as the electronic control unit 10 will now be described with reference to the flow chart shown in FIG. 2.
In step S1, initialization is performed, that is, the respective states of the input/output ports are set, a control flag is cleared, parameters are initialized, and similar processes are performed. Thereafter, in step S2, the respective states of the input ports P1 through P8 are read.
In step S3, judgment is done as to whether the low-temperature switch SW6 is ON or not. If it is not ON (that is, it is OFF), the LED is turned off in succeeding step S23 and control proceeds to step S4. If the low-temperaure switch SW6 is ON, the LED is turned on in step S22, and control proceeds to step S11 in which "0(zero)" is set in a control flag F and then to step S9.
In step S9, because the control flag indicates "0", control proceeds to step S14. In step S14, a standby process is performed, that is, the constant-speed running control process is released. Thereafter, in step S24, the solenoids SL1 and SL2 are switched off, and control returns to step S2.
In step S4, judgment is done as to whether the stop switch SW1 is ON or not. If it is not ON, control proceeds to step S5. If the stop switch SW1 is ON, similarly to the case the low-temperature switch SW6 is ON, in step S11, "0" is set in the control flag F. After passing through step S9 and performing the standby process in step S14, control returns to step S2.
In step S5, judgment is done as to whether the clutch switch SW2 is ON or not. If it is not ON, control proceeds to succeeding step S6. If the clutch switch SW2 is ON, similarly to the case the low-temperature switch SW6 is ON or the case the stop switch SW1 is ON, "0" is set in the control flag F in step S11. After passing through step S9 and performing the standby process in step S14, control returns to step S2.
Thus, the stop switch SW1 and the clutch switch SW2 act as cancel switches.
In step S6, judgment is done as to whether the setting switch SW3 is ON or not. If it is not ON, control proceeds to succeeding step S7. If the setting switch SW3 is ON, control proceeds to succeeding step S12. In step S12, "2" is set in the control flag F, and control proceeds to step S9. In step S9, because the control flag indicates "2", control proceeds to step S16. In step S16, a setting process is performed, that is, a given car speed is stored. Then, control proceeds to step S19.
In step S19, "1" is set in the control flag. Thus, unless the control flag is reset in other succeeding control loops, the constant-speed running control process of step S15 is performed forever.
In step S7, judgment is done as to whether the resume switch SW4 is ON or not. If it is not ON, control proceeds to succeeding step S8. If the resume switch SW4 is ON, control proceeds to step S13 in which "3" is set in the control flag F, and control proceeds to step S9. In step S9, because the control flag indicates "3", control proceeds to step S17. In step S17, a resume process is performed, that is, the constant-speed running control process previously set is released and a process of causing the car speed to revert to the previously-stored car speed is performed. Thereafter, "1" is set in the control flag F in step S20, and control returns to step S2.
In step S8, judgment is done as to whether the acceleration switch SW5 is ON or not. If it is not ON, control proceeds to step S9, after this step a process corresponding to the indication of the control flag lately set being performed. If the acceleration switch SW5 is ON, control proceeds to step S10 in which "4" is set in the control flag F, and control proceeds to step S9. In step S9, because the control flag indicates "4", control proceeds to step S18 in which an acceleration control process is performed, that is, the car speed is increased, a new car speed is stored, and a process commencing the constant-speed running control process is performed. Thereafter, "1" is set in the control flag F in step S21, and control returns to step S2.
As described above, according to the foregoing embodiment, when the ambient temperature lowers, this is detected by the temperature switch means, whereby the constant-speed running control process can be inhibited.
Further, in case the temperature switch means is actuated to inhibit the constant-speed running control process, this condition can be indicated. Thus, a driver can be informed of the fact that the constant-speed running control process has been inhibited because of a low-temperature state, and conversely, he can also be informed of the fact that such an inhibited state has been released.
For reference, during the constant-speed running control device being in operation, if the ambient temperature lowers to actuate the temperature switch means, the low-temperature release means releases the control of the actuator means to stop the operation of the constant-speed running control device, whereby the standby state can be brought. Thereafter, until the ambient temperature rises to terminate the actuated state of the temperature switch means, the control circuit maintains the standby state, hence, the constant-speed running control process is inhibited.
Although in the foregoing embodiment the standby process is put in operation if the low-temperature switch is actuated, such a control process may be modified so as to perform the initialization process of step S1. Further, the electronic control unit should not be limited to the type realized by the micro computer.
As described hereinabove, according to the present invention, erroneous operation of the constant-speed running control device that would otherewise be caused owing to lowering of the ambient temperature can be prevented from occurring, and the reliability, particularly in a cold northern district, of the constant-speed running control device can be enhanced remarkably. | A constant-speed running control device is provided, which comprises car speed detecting means for detecting the current car speed of a vehicle, memory means for storing a given car speed, an actuator for controlling a throttle valve, setting means for causing the memory means to store the given car speed, releasing means for releasing the control of the actuator, electronic control means for controlling the actuator in such a direction as to cause the difference between the stored car speed held in the memory means and the current car speed detected by the car speed detecting means to disappear, temperature detecting means, and low-temperature release means for actuating the releasing means in response to the output of the temperature detecting means, whereby the control of the actuator is released through the releasing means when an ambient temperature lowers to thereby prevent erroneous operation and enhance reliability. | 1 |
TECHNICAL FIELD
This invention relates to a method to deposit thin films. Specifically, a method to sputter deposit multilayer thin films on a substrate by bombarding a target with ions produced by a radio-frequency excited ion beam gun is disclosed.
BACKGROUND OF THE INVENTION
Many schemes and apparatus have been devised to produce multilayer thin films. These films are used in semiconductor fabrication, optical waveguides, and highly reflective mirrors such as those used in ring laser gyroscopes. Sputter deposition usually takes place in a vacuum chamber where a target material is impacted by ion beams to sputter material off the target by collision mechanics. This sputtered material would then be deposited on a substrate to produce the device.
Several problems have been associated with prior art systems. It has been difficult to generate a beam of ions which is free of contaminants and of a high enough energy to be effective. It has also been difficult to impart enough energy to the sputtered material to ensure a uniform deposited film of a known thickness, density and surface smoothness. The major problems, therefore, have been with the source of the ions to perform the sputtering. Ionizing sources and methods have, therefore, been the subject of significant work.
The simplest of these ionizing methods was to use a filament, or thermionic emitter, to generate electrons within the ionization chamber. The electrons created by the filament collided with the gas molecules, knocking off electrons from the gas molecules to cause the molecules to become positively charged. This method, although operable, had several disadvantages. The filaments tended to have a short life. Because the filaments were thermionic emitters and were at a negative electrical potential relative to the ionized gas, material was sputtered or evaporated off of the filament which caused contamination to be introduced into the ion beam.
An improvement upon the filament type of ion generation was the introduction of a hollow cathode. This eliminated the need of a filament and greatly increased the operational life. Potentials for contamination of the ion beam due to materials present in the hollow cathode were still present.
Further advances of ion beam generating devices included using a high-frequency generator coupled to either plates or coils within the chamber to ionize the gas molecules through excitation by the high-frequency energy. These materials, especially coils within the plasma field, also created contamination in the ion beam. An advancement, placing a coil outside the gas chamber helped to eliminate this contamination. However, external magnetic fields were usually required to contain the plasma within the chamber, enhancing ionization efficiency and to prevent arcing from the plasma to various components within the chamber. The arcing could cause a rapid degradation of the plasma and ultimate destruction of the components within the chamber. Most of the attempts to use high-frequency plasma generation also required that the generator coil be cooled by internal water means. This introduced the problem of having each end of the coil at the same potential, preferably ground potential, to prevent the high-frequency energy from being bled off to ground. Elaborate matching networks, or tight control of the length of the waveguide or coil, were required in order to accomplish these goals.
A need, therefore, exists for being able to generate a beam of positively charged gas molecules without contaminating the beam by the plasma touching contaminating fixturing within the chamber and without the need of water cooled coils or external magnetic fields.
A need also exists to translate substrates within the deposition chamber to insure uniform deposition.
A further need exists to be able to translate targets within the deposition chamber to produce multilayer films.
SUMMARY OF THE INVENTION
The present invention deposits thin films in either a single layer or multiple layers on a substrate. A supply of inert gas is fed to a radio-frequency excited ion beam gun where the gas is ionized into positively charged gas ions into a plasma. The gas ions are extracted from the ion beam gun in a stream or column of ions. The stream of ions is shaped by shutters and directed against targets within a vacuum chamber. The target material is held in a translatable target holder positioned at an angle to the beam. Multiple targets may be held by the holder and selectively translated into and out of the stream of ions.
A plurality of substrates are held above the target so that target molecules sputtered off the target by collision mechanics may be deposited on the substrates. The substrates are mounted in a planetary holder which rotates the substrates into and out of the stream of sputtered target molecules to allow uniform deposition.
It is an object of the invention to uniformly deposit thin films on a substrate.
It is a further object of the invention to provide inexpensive and repeatable thin film deposition using ions created in a radio-frequency excited ion beam gun.
It is another object of the invention to deposit multilayer films of different material on a plurality of substrates.
These and other objects of the invention will be apparent from the following detailed description of a preferred embodiment when read in connection with the appended drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side view of a sputter deposition apparatus as described in the present invention.
FIG. 2 is a top view of a sputter deposition apparatus as described in the present invention.
FIG. 3 is a longitudinal cross-section of the ion producing chamber of the ion beam gun of the present invention.
FIG. 4 is a partially cut away longitudinal view of the ion beam gun of the present invention.
FIG. 5 is a perspective blow-up view of the components of the ion producing chamber of the ion beam gun of the present invention.
FIG. 6 is an electrical block diagram showing the electrical components and their interconnection to the components of the ion producing chamber of the ion beam gun of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to FIG. 1, a vacuum chamber 20 is provided which can be evacuated to a very low pressure by vacuum pump 22. In a preferred embodiment, the vacuum chamber 20 operates at a pressure of 1×10 -4 Torr Mounted to the wall of the vacuum chamber 20 is an ion gun 30, whose details and operation will be explained below. The ion gun 30 is supplied with a source of inert gas 38 which, in the preferred embodiment, is xenon. Other inert gases, such as argon, have also been used with equal results. The ion beam gun 30 produces a stream of positively charged ions 42 by means of radio-frequency excitation, as will be explained below. This ion beam 42 is extracted from ion gun 30 and progresses through a plurality of shutters 32 and 34. These shutters 32 and 34 are, in the preferred embodiment, circular titanium plates having apertures of various diameters through which the ion beam 42 is directed and shaped into a coherent beam of positively charged inert gas ions.
A translatable target holder 40 is provided to hold a target 50 at an acute angle to the ion beam 42. The ion beam impinges the target 50 and knocks material off the target in the direction of the solid arrows of FIG. 1. The material sputtered off the target is directed toward a plurality of substrates 50 and 52 which are held by a substrate holder 60. Substrate holder 60 has an axis 61 about which the substrate holder 60 can rotate. There are a plurality of substrate holders, such as shown as substrate holders 60 and 62 in FIG. 1. Each of the substrate holders has a centrally located central axis, such as axis 63 for substrate holder 62. All of the substrate holders are held by a common carrier 70. The common carrier 70 has a central axle 71 about which the carrier can rotate. This arrangement allows the individual substrates 52, 54, etc. to follow an elliptical retrograde motion within the vacuum chamber 20. As can be seen if FIG. 1, as the carrier 70 rotates and the individual substrate holder 60 rotate on their axis, the substrates 52 and 54 are rotated into and out of the stream of sputtered material shown by the solid arrows in FIG. 1.
Because the beam of ions 42 are positively charged, a neutralizer 90 is provided to provide electrons to combine with the positive molecules to form a stream of material with a net zero electrical charge. This prevents positive ions from building up inside the vacuum chamber 20 and extinguishing the ion beam 42. Because, as will be explained below, the majority of the materials used in the sputter deposition of thin films for this invention are oxides, a source of oxygen 80 is provided to maintain a proper stoichiometric ratio for efficient deposition.
Referring now to FIG. 2, it can be seen that the target No. 2 50 can be of one material and another target, target No. 1 51, can be of another material. FIG. 2 also shows how the target holder 40 can translate the targets into and out of the ion beam 42. In this manner, a multitude of different materials can be sputtered deposited on the substrates one layer upon an additional layer without stopping the deposition process. In a preferred embodiment shown in FIG. 2, target material No. 1 51 can be silicon dioxide. In an alternate embodiment, target material No. 1 51 may be silicon dioxide doped with additional materials such as titanium dioxide or zirconium dioxide. Similarly, target No. 2 50, in a preferred embodiment, may be titanium dioxide. In an alternate embodiment, target No. 2 50 may be zirconium dioxide. In a further embodiment, target No. 2 50 may be titanium dioxide doped with between 5% to 20% silicon dioxide. While in a further embodiment, target No. 2 50 may be zirconium dioxide doped with between 5% to 20% silicon dioxide. In this manner, multiple layer optical films may be deposited having alternating layers of silicon dioxide, titanium dioxide, zirconium dioxide or various combinations of silicon dioxide-titanium dioxide mixture or silicon dioxide-zirconium dioxide mixture.
Referring now to FIG. 3, the ion beam gun has a chamber, or vessel, 100 for containing a gas to be ionized. The vessel 100 has side walls 200 which, in the preferred embodiment, is a high temperature cylindrical glass tube. Side wall 200 can, of course, be of any geometric shape such as square, wherein there would be side walls, or other geometric shapes. In an alternate embodiment, the side walls 200 can be made of fused quartz. It has been found, however, that utilizing a high temperature glass for side walls 200 will cut down on the ultraviolet radiation which emanates through the transparent side walls. The only requirement is that the material be high temperature dielectric material so that it does not melt or conduct radio-frequency energy and also be of sufficient integrity that there be minimal sputtering or loss of materials from the inside of the side walls caused by the ionized gas.
The vessel, or chamber, 100 also has a first closed end 202 made of a suitable material such as aluminum and a second end 204 having an aperture therethrough, again made of a suitable material such as aluminum. The aluminum makes an ideal material because it is conductive and it is not affected by the plasma because the plasma is shielded from the aluminum first end 202 and the second end 204 by other components within the vessel 100, as will be explained below.
A seal 206 is provided to mate between the side wall 200 and the first end 202 to form a gas-tight seal. A similar gasket 208 is designed to fit between the side wall 200 and the second end 204, again, to form a gas-tight seal. Suitable through bolts 210 connect the first side wall 202 to the second side wall 204. Because, as will be explained below, the first end 202 and the second end 204 are at different electrical potentials, it is necessary to electrically isolate through bolts 210 from first end 202. A suitable insulator 220 is provided in the first end 202 to prevent the through bolt 210 from being impressed with the electrical signals which will ultimately be placed on the first end 202. A suitable nut 222 completes the assembly to contain the side wall 200 between the first end 202 and the second end 204. A coil 230, in a preferred embodiment constructed of copper tubing, is wound about the outside of the side wall 200, but spaced apart from the side wall 200 by suitable insulators 232. A gas inlet 240 is provided in the first end 202 to allow gas to be injected into the chamber 100.
A first anode plate 242 and a second anode plate 244 are electrically and mechanically connected to a center post 246 which, in turn, is electrically and mechanically connected to the first end 202.
Adjacent to the second end 204 inside the chamber 100 is a resonator 250. Resonator 250 is, in the preferred embodiment, a flat circular titanium plate having an aperture therethrough and outstanding flange about the inside perimeter of the aperture in second end 204. The resonator 250 is electrically insulated and mechanically separated from the second end 204 by a glass insulating plate 252. The resonator 250 is mechanically attached to an insulator 254 by means of titanium screws 256. Within the aperture of the second end 204 is a multi-apertured screen grid 260 and a multi-apertured accelerator grid 262 which are spaced apart and held by insulating spacers 270 which attach to the insulator 254.
Referring now to FIG. 4, an additional through bolt 212, an additional insulating spacer 224 and attachment nut 226 are shown in more detail. Similarly, an additional standoff insulator 234, similar to 232, is shown holding the coil 230.
The coil 230 is a length of conductive material wound into a solenoid of between three and four turns about the outside of side walls 200. The coil 230, in a preferred embodiment, is approximately three and one-half turns about the side walls 200 of 3/8 inch diameter thin wall copper tubing. The coil 230 has a first end 280 which, in the preferred embodiment, is attached to the second end of the chamber 204 and a second end 284 which has an electrical connection which will be explained below. In addition, an intermediate point has an electrical connector 282 attached. The intermediate point is approximately one-third of a turn from the first end 280 of the coil 230.
The complete gun assembly has a fan mounting flange 290 which is spaced apart from the first end 202. The flange has an aperture with a fan 292 located therein. Fan 292 forces cooling air through the ion beam gun between the outside of the side wall 200 and a metal protective shield 298. The air exits from exit holes 300 located about the periphery of the shield 298 in the area of the second end 204.
As can be seen in FIG. 4, a source of gas 38 is transmitted by means of tubing 296 to the gas inlet port 240 to be introduced into the chamber 100.
Referring now to FIG. 5, a more detailed description of the various components can be seen. In the preferred embodiment, the anode consists of two plates, a first anode plate 242 and a second anode plate 244 spaced apart and mounted on a common central post 246. The post 246 is mechanically and electrically connected to the first end plate 202 of the vessel.
The first anode plate 242 and the second anode plate 244 each have a plurality of slits 245 radiating outwardly from the center post 246 toward the perimeter of each plate. In the preferred embodiment, there are eight slits in both the first anode plate 242 and the second anode plate 244. The second anode plate 244 is rotated, or orientated, on the center post 246 in such a way that the slits 245 in the first anode plate 242 do not overlap the slits 245 in the second anode plate 244. The slits prevent any eddy currents from being induced in either the first anode plate 242 or the second anode plate 244 by the radio-frequency energy impressed on the coil 230. The slits 245 also provide a gas path to uniformly disperse and diffuse the gas within the vessel.
Second anode plate 244 is spaced apart from the side wall 200 of the vessel 100 and from the first end plate 202 so that no plasma will be generated between the second anode plate 244 and the first end plate 202. Similarly, the first anode plate 242 is spaced apart from the side wall 200 and the second anode plate 244 in such a manner as to prevent a plasma from being generated between the first anode plate 242 and the second anode plate 244.
Experimentation has shown that arcing could occur from the plasma to the coil 230 through the insulating side wall 200 if the coil 230 is placed directly on the insulating side wall 200. Another problem with placing the coil 230 directly against the insulating side wall 200 is that material from the inside surface of the side wall 200 could sputter off the inside of the side wall 200, decreasing the side wall 200 strength and contaminating the ion beam with the sputtered material. Placing the coil 230 directly against side walls 200 can also cause hot spots on side walls 200 which can lead to additional problems.
Spacing the coil 230 apart from the side wall 200 to provide an air gap between the coil 230 and the side wall 200 minimizes these problems. The coil 230, in the preferred embodiment, is spaced apart from the side wall 200 by means of a plurality of insulating spacers, such as spacer 232 and spacer 234. This not only prevents arcing, contamination and sputtering of the side wall 200, but also provides an air path between the coil 230 and the side wall 200 to allow cooling air from the fan 292 to further cool the coil 230 and the surface of the side wall 200.
Again, referring to FIG. 5, more specific detail of screen grid 260 and accelerator grid 262 can be seen. The screen grid 260 has a plurality of apertures. These apertures in the screen grid 260 are holes approximately 0.075 inches in diameter and having a density of approximately 100 holes per square inch. The accelerator grid 262, similarly, has a plurality of apertures. The apertures in the accelerator grid 262 are approximately 0.050 inches in diameter and have a density of approximately 100 holes per square inch. Both the screen grid 260 and the accelerator grid 262 are, in the preferred embodiment, constructed out of a graphite material. The apertures in the screen grid 260 and the apertures in the accelerator grid 262 are aligned one to the other.
Referring now to FIG. 6, the electrical interconnection of the various components to the ion beam gun can be seen in detail. A direct current power supply 302, which is adjustable between approximately 1,000 volts and 2,000 volts, is provided to supply electrical potential through filter 304 to the first end 202 of the ion beam gun through an electrical connection to the center post 246. Power supply 302 also supplies its voltage through a filter 306 to the resonator 250. Similarly, the same voltage is applied through filter 308 to the screen 260. This positive DC potential, which in the preferred embodiment, has been found to be effective at 1,750 volts, is used to partially contain the plasma and prevent the plasma from contacting either the first anode plate 242, the resonator 250 or the screen 260. The power supply 302 is a second power supply.
The first power supply is the radio-frequency generator 320. The radio-frequency generator 320 can supply energy having a frequency which is variable between 6 megahertz to 50 megahertz and power between a few watts to several hundred watts. The radio-frequency generator 320, in the preferred embodiment, outputs a standard industrial frequency of 13.56 megahertz. The radio-frequency energy is sent through a matching circuit 322 and connected to the intermediate point 282 of the coil 230. The first end of the coil 230 is connected to the second end plate 204 which is grounded and, therefore, the first end of the coil 230 is at ground potential. The second end 284 of the coil 230 is connected to a first end of a variable capacitor 324, which is variable between the range of 5 microfarads to 100 microfarads. A second end of variable capacitor 324 is connected to ground.
A plurality of capacitors 330, 332 and 334, typically 0.01 picofarads capacitors, have their first end connected to the first end 202 of the vessel 100. A second end of capacitors 330, 332, and 334 is connected to ground. In the preferred embodiment, as shown in FIG. 4, this connection is made through the through bolts, such as through bolt 210. Capacitors 330, 332 and 334 drain off any induced radio-frequency charge induced in the first end 202 by the radio-frequency energy supplied to coil 230. It should be noted that the RF energy supplied to coil 230 does induce eddy currents in resonator 250. It has been found that the inducing of the eddy currents in resonator 250 increases the beam strength of the output beam of the ion beam gun by approximately 20% when used in conjunction with the capacitors 330, 332 and 334. A third power supply 340 supplies a negative DC potential through filter 342 to the accelerator grid 262. This extracts the ions from inside chamber 100 to be used for the purposes intended.
It has been found that by using an input wattage from the RF generator of approximately 550 watts that an output beam of 1,750 volts at 200 milliamperes of current can be achieved.
OPERATION
In operation, sample holders 60 and 62 are removed from vacuum chamber 20 and loaded with a plurality of substrates 52, 54 etc. The substrate holders 60 and 62 are then inserted onto carrier 70 along with a plurality of other holders holding a plurality of substrates.
A plurality of targets 50 and 51 are placed on target holder 40 within the vacuum chamber 20. The vacuum chamber 20 is then closed and sealed and evacuated by vacuum pump 22. The ion beam gun 30 is then supplied with an inert gas 38 and activated, as will be explained below.
A supply of inert gas, such as xenon or argon, is supplied through source 38 into the inside of chamber 100 at a flow of 3.5 standard cubic centimeters per minute. The gas is diffused through slots 245 in second anode plate 244, and slots 245 in the first anode plate 242 and about the perimeter of anode plates 242 and 244 to uniformly disperse within the chamber 100.
The coil 230 is supplied with radio-frequency energy from the first power supply, radio-frequency generator 320 through matching circuit 322. The frequency of the radio-frequency generator is, in the preferred embodiment, 13.56 megahertz with an output power of 550 watts. The matching circuit 322 matches the output impedance of the radio-frequency generator 320 to a transmission line impedance of 50 ohms. The transmission line from the matching circuit 322 is connected to the intermediate point 282 on coil 230 so that the impedance from the intermediate point 282 to ground is near 50 ohms when the plasma is generated and operating.
The first end 202 of vessel 100 and, subsequently, the anode plates 242 and 244 are supplied with 1,750 volts DC from the second power supply 302. The second power supply 302 also supplies 1750 volts DC to the resonator 250 and screen grid 260.
The ions thus generated are extracted from the vessel 100 by applying a second direct current voltage, which in the preferred embodiment is a negative 100 volts, from the third power supply 340 onto accelerator grid 342. In the preferred embodiment described above, the output of the ion beam has been determined to be 200 milliamperes at 1,750 volts.
Having illustrated and described the principles of the invention in a preferred embodiment, it should be apparent to those skilled in the art that the invention can be modified in arrangement and detail without departing from such principles. I claim all modifications coming within the spirit and scope of the following claims. | The present invention discloses a method to deposit thin films on a substrate. An inert gas is introduced into a radio-frequency excited ion beam gun. The ions thus produced are directed to a target where molecules of the target are sputtered off and deposited on a substrate. A method of translating different targets into the ion beam is provided in order to produce multilayer films with different properties in each layer. A method is also provided to rotate the substrates into and out of the path of the sputtered molecules to insure a uniform film. | 2 |
FIELD OF THE INVENTION
The present invention generally relates to a medical device for surgical procedures and specifically to a suturing assembly comprising hollow needle.
BACKGROUND OF THE INVENTION
Surgical procedures these days tend to minimize cut of body tissue by utilizing advanced technology medical devices. Consequently, alternative suturing procedures have to be applied for addressing new substantially further complicated conditions facing the suturing procedures. In the procedure of anastomosis of the urethra and bladder during radical retro-pubic prostatectomy, for example, the attachment of the urethral stump to the bladder neck is particularly difficult and carried out semi-automatically by a surgical medical device. The prior art of suturing manually cannot be applied in these surgical procedures without further body tissue cutting that provides an easier access to the tissue area. The new surgical procedures utilizing for example technologically advanced catheters can be implemented by combining the insertion of catheters into body tubes, tracts or canals and thus restricting the required body tissue cuts. When these surgical procedures are being used, new technologically advanced suturing methods have to be applied for utilizing the advantages of the new surgical procedures to their fullest. Apparently there is a need for suturing devices capable of meeting the challenging conditions imposed by the new surgical procedures.
SUMMARY OF THE INVENTION
It is an object of the present invention to disclose a suturing needle having a hollowed distal portion.
Another object of the present invention is to disclose a suturing needle having a hollowed distal portion, comprising a notched open bore located at said needle's very distal end.
Another object of the present invention is to disclose a suturing assembly comprising said suturing needle with a hollowed distal portion.
Another object of the present invention is to disclose a suturing assembly comprising a needle with a main longitudinal axis having a sharpened tip and hollow distal portion, defining a notched open bore at said needle very distal end.
Another object of the present invention is to disclose the needle as defined in any of the above, wherein said hollow portion of said needle having a bore is adapted to accommodate a suture.
Another object of the present invention is to disclose the suturing assembly as defined in any of the above, wherein said hollow portion of said needle having a bore is adapted to accommodate a suture.
Another object of the present invention is to disclose the needle as defined in any of the above, further comprising a proximal portion, wherein said proximal portion is adapted for coupling with a surgical device.
Another object of the present invention is to disclose the suturing assembly as defined in any of the above, wherein said proximal portion is adapted for coupling with surgical device.
Another object of the present invention is to disclose the suturing assembly as defined in any of the above, further comprising a suture; said suture is extended from said bore.
Another object of the present invention is to disclose the suturing assembly as defined in any of the above, said assembly further comprising a suture, reversibly mounted within said bore.
Another object of the present invention is to disclose the suturing assembly as defined in any of the above, wherein said suture comprising at least one anchoring stopper.
Another object of the present invention is to disclose the suturing assembly as defined in any of the above, wherein said anchoring stopper is spherically shaped.
Another object of the present invention is to disclose a suturing assembly as defined in any of the above, wherein said anchoring stopper is shaped in a shape consisting of a group of various triangles.
Another object of the present invention is to disclose the suturing assembly as defined in any of the above, wherein said anchoring stopper comprising a plurality of rods, umbrella like shaped, having a main axis substantially coinciding with the longitudinal axis of said suture.
Another object of the present invention is to disclose the suturing assembly as defined in any of the above, wherein said hollow portion of the needle is having a bore, adapted to accommodate a suture.
Another object of the present invention is to disclose the suturing assembly as defined in any of the above, said assembly further comprising a proximal portion wherein said proximal portion is adapted for coupling with surgical device.
Another object of the present invention is to disclose the suturing assembly as defined in any of the above, said assembly further comprising a suture; said suture is extended from said bore after inserting said suture into said bore.
Another object of the present invention is to disclose the suturing assembly as defined in any of the above, said assembly further comprising a suture; said suture is extended from said bore via said notch after inserting said suture into said bore.
Another object of the present invention is to disclose the suturing assembly as defined in any of the above, said assembly further comprising at least one anchoring stopper.
Another object of the present invention is to disclose the suturing assembly as defined in any of the above, wherein said suture comprising at least one anchoring stopper.
Another object of the present invention is to disclose the suturing assembly as defined in any of the above, wherein said anchoring stopper is spherically shaped.
Another object of the present invention is to disclose the suturing assembly as defined in any of the above, wherein said anchoring stopper is shaped in a shape consisting of a group of various triangles.
Another object of the present invention is to disclose the suturing assembly as defined in any of the above, wherein said anchoring stopper, comprising a plurality of rods, umbrella like shaped, having a main axis substantially coinciding with the longitudinal axis of said of said suture.
Another object of the present invention is to disclose method of suturing. The method comprising steps selected from a group consisting of obtaining a suturing assembly, comprising (i) a suturing needle with a hollowed distal portion with an open bore at the distal end; and, (ii) a suture reversibly mounted within said bore; suturing a body tissue by piercing said tissue with said distal portion of said needle, until said needle's distal portion extends beyond said pierced tissue; and, retrieving said needle backwards (retrograde) while said suture end, i.e., the end which was inserted into said needle bore, is disengaging from said suturing needle and retained beyond said pierced tissue.
Another object of the present invention is to disclose the suturing method as defined in any of the above, wherein disengaging said retrieved needle from said suture is provided by an anchoring stopper retaining the suture beyond said pierced tissue.
Another object of the present invention is to disclose the method as defined in any of the above, wherein said suturing is provided manually.
Another object of the present invention is to disclose the method as defined in any of the above wherein said suturing is provided automatically by coupling said needle, especially its proximal portion, with a surgical device.
Another object of the present invention is to disclose the method as defined in any of the above, said assembly further wherein said suturing is provided automatically by coupling a plurality of N needles, with a surgical device. N is integer number, being in a non-limiting manner between 2 to 10.
BRIEF DESCRIPTION OF THE FIGURES
The object and the advantages of various embodiments of the invention will become apparent from the following description when read in conjunction with the accompanying drawings wherein:
FIG. 1 a schematically represents an out-of-scale illustration of the distal portion of the suturing needle according to one embodiment of the present invention;
FIG. 1 b schematically represents an out-of-scale illustration of the distal portion of the suturing needle with the inserted suture according to another embodiment of the invention;
FIG. 2 schematically represents an out-of-scale side view of distal portion of the suturing needle depicting the bore inside the needle according to another embodiment of the invention;
FIG. 3 schematically represents an out-of-scale illustration of the suturing needle combined with an inserted suture according to another embodiment of the invention;
FIG. 4 schematically represents a flow chart of a method according to another embodiment of the invention;
FIG. 5 schematically represents an out-of-scale illustration of the suturing needle with the extended suture at two distinct suturing positions according to another embodiment of the invention; and,
FIG. 6 schematically represents out-of-scale illustration of variations of the anchoring according to yet another embodiment of the invention.
DETAILED DESCRIPTION OF THE EMBODIMENTS
The following description is provided alongside all chapters of the present invention, so as to enable any person skilled in the art to make use of said invention and sets forth the best modes contemplated by the inventor of carrying out this invention. Various modifications however, will remain apparent to those skilled in the art, since the generic principles of the present invention have been defined specifically to provide a suturing needle having a hollowed distal portion; a suturing assembly comprising a needle with a main longitudinal axis having a sharpened and hollow distal portion, defining a notched open bore at said needle very distal end; and a method of suturing comprising obtaining a suturing assembly, comprising (i) a suturing needle with a hollowed distal portion with an open bore at the distal end; and, (ii) a suture reversibly mounted within said bore; suturing a body tissue by piercing said tissue with said distal portion of said needle, until said needle's distal portion extends beyond said pierced tissue; and, retrieving said needle backwards (retrograde) while said suture end, i.e., the end which was inserted into said needle bore, is retained beyond said tissue.
Reference is now made to FIG. 1 a presenting a schematic illustration of the distal portion of the needle. The distal portion of the needle 10 is apt to piercing a body tissue by a sharpened tip 1 . The distal portion 10 is hollow and further comprises a bore and least one notch 2 at the very distal end of the bore which are used to accommodate a suture.
Reference is now made to FIG. 1 b presenting a schematic illustration of a suturing assembly of the distal portion of the suturing needle combined with the suture. The suturing assembly 30 comprises the distal portion of the needle 10 combined with a suture 20 inserted through the notch 2 into the bore. Notch 2 is used for guiding the suture 20 during suture insertion and for retaining the suture inserted to the needle 10 while the suturing assembly 30 is penetrating the body tissue.
Reference is now made to FIG. 2 presenting a schematic illustration of a side view of the distal portion of the suturing needle. The distal portion of the suturing needle 10 and the sharpened tip 1 are drawn by solid lines, while the concealed notch 2 bore 4 , are drawn by dashed lines.
Reference is now made to FIG. 3 presenting a schematic illustration of the distal portion of the needle 10 along with the distal portion of the suturing needle 30 . As indicated, the distal portion of the needle is characterized by a main longitudinal axis. The suturing needle includes the suture 20 with a first portion retained in the bore and the notch 2 of the needle. A second portion of the suture 20 , adjacent to the first portion extends alone the outer surface of the needle 30 . An anchoring stopper 21 is appended to the suture 20 between the first and second portions and used to keep the suture inside the body tissue by blocking the motion of in the proximal direction when the needle is retrieved.
Reference is now made to FIG. 4 presenting a schematic illustration of a flow chart depicting the method of body tissue suturing. In step 51 , the surgeon inserts the suture into the bore of the distal portion of the suturing needle for preparing the needle-suture assembly. In the following step 52 , the surgeon pierces the tissue for penetrating the suturing needle combined with the suture into the tissue until the suturing needle tip and the anchoring stopper appended to the suture extend beyond the inner wall of the tissue. In the following step 53 the surgeon retrieves the suturing needle so that the needle is traversing in the proximal direction. When retrieved, the suturing needle disengages from the suture since the suture is retained in the tissue by the appended anchoring stopper preventing movement of the suture in the proximal direction. The suture can be tied later by the surgeon to another nearby suture inserted similarly into the body tissue.
Reference is made now to FIG. 5 presenting a schematic illustration showing side by side the needle-suture assembly at some time during tissue penetration and at some time during retrieving. Identical parts of the assembly shown at the distinct instances during the suturing process are designated by the letters “a” and “b”. The needle-suture assembly 30 is depicted after piercing the body tissue wall 42 and penetrating through the body tissue 40 until the anchoring stopper 21 a is beyond the inside wall of body tissue 40 . Needle 10 b is depicted when retrieved from the body tissue while the suture 20 is disengaged from needle 10 b and retained inside the body tissue by the anchoring stopper 21 b blocking the movement out.
Reference is now made to FIG. 6 presenting a schematic illustration of two distinct embodiments of the anchoring stopper appended to the suture. The stopper is structured to minimize interfering with the needle-suture penetration into the body tissue yet provide the blocking action to the suture when the stopper is located beyond and near the inside wall of the body tissue when the needle is retrieving. Stopper 21 is shaped like a triangle consisting of a group of various triangular shapes. Another embodiment of the anchoring stopper is illustrated by Stopper 22 and stopper 23 . In this embodiment the stopper is an umbrella like structure constructed by a plurality of rods. When the suturing assembly is penetrating the tissue, stopper 22 is shaped like a closed umbrella thus minimally interfering with the needle suture penetration into the tissue. Stopper 23 of this type is depicted when stopper getting to the internal wall of the body tissue whereas the stopper becomes shaped like an opened umbrella and thus provides the stopper blocking function. | A suturing needle is disclosed having a main longitudinal axis, a distal sharp portion and proximal portion along said axis. The distal portion is hollowed, and the hollow is approximately parallel to said axis. A further embodiment of the suturing needle is disclosed such that the distal portion comprises a notched open bore located at the needle's extreme distal end. Other embodiments of the suturing assembly are described accommodating a suture in the needle bore. | 0 |
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a Continuation-in-part of a 35 USC 371 patent application Ser. No. 09/958,050 filed on Oct. 2, 2001 in the United States Patent and Trademark Office, for which an International Patent Application No. PCT.GB01.03495 was filed on Aug. 3, 2001, which claims priority to United Kingdom Patent Application No. GB 0019172.6 filed Aug. 5, 2000.
FIELD OF THE INVENTION
The present invention relates to a novel composition containing an anti-inflammatory and anti-allergic compound of the androstane series and to processes for its preparation. The present invention also relates to pharmaceutical formulations containing the composition and to therapeutic uses thereof, particularly for the treatment of inflammatory and allergic conditions.
BACKGROUND OF THE INVENTION
Glucocorticoids which have anti-inflammatory properties are known and are widely used for the treatment of inflammatory disorders or diseases such as asthma and rhinitis. For example, U.S. Pat. No. 4,335,121 discloses 6α, 9α-Difluoro-17α-(1-oxopropoxy)-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester (known by the generic name of fluticasone propionate) and derivatives thereof. The use of glucocorticoids generally, and especially in children, has been limited in some quarters by concerns over potential side effects. The side effects that are feared with glucocorticoids include suppression of the Hypothalamic-Pituitary-Adrenal (HPA) axis, effects on bone growth in children and on bone density in the elderly, ocular complications (cataract formation and glaucoma) and skin atrophy. Certain glucocorticoid compounds also have complex paths of metabolism wherein the production of active metabolites may make the pharmacodynamics and pharmacokinetics of such compounds difficult to understand. Whilst the modern steroids are very much safer than those originally introduced, it remains an object of research to produce new molecules which have excellent anti-inflammatory properties, with predictable pharmacokinetic and pharmacodynamic properties, with an attractive side effect profile, and with a convenient treatment regime.
We have now identified a novel glucocorticoid compound and a crystalline composition thereof which substantially meets these objectives.
SUMMARY OF THE INVENTION
Thus, according to one aspect of the invention, there is provided a crystalline chemical composition comprising a compound of formula (I)
in which the crystal lattice is stabilised by the presence of a guest molecule, characterised in the crystalline composition is of space group P2 1 2 1 2 1 having unit cell dimensions of about 12.1±0.6 Å, 14.9±0.7 Å, and 16.2±0.8 Å when determined at either 120K or 150K (hereinafter “a composition of the invention”)
The nature of the crystal lattice can be seen by reference to FIG. 1 which shows the spacial arrangement of 4 molecules of steroid and 4 guests within a single unit cell for two example compositions and FIG. 2 A and FIG. 2B which shows detail of the spacial arrangment between steroid and guest molecule for the same two example compositions.
We have determined the XRPD profiles for a large number of compositions according to the invention. These XRPD profiles are also apparently characteristic of the crystalline composition according to the invention. In particular they exhibit one or more of the following 5 features when determined at ambient temperature (eg around 295K):
(a) A peak in the range of around 7.8-8.2; and
(b) A peak in the range of around 8.8-9.6; and
(c) A peak in the range of around 10.5-11.1
(d) A peak in the range of around 15.0-15.8
(e) A peak, often (but not always) associated with a pair of peaks, in the range of around 21.2-21.8
Typically they exhibit 2 or more typically 3 or more of the above 5 features, especially 4 and particularly all 5 of the above 5 features.
The XRPD profiles of compositions of the invention when crystallographically pure also preferably exhibit one or more of the following 2 features when determined at ambient temperature (eg around 295K):
(a) Absence of a peak at around 7 (eg around 6.8-7.4) which is associated with the profile of unsolvated Form 1, 2 and 3 polymorphs and present at particularly high intensity in Forms 2 and 3;
(b) Absence of a peak at around 11.5 (eg around 11.3-11.7) which is associated with the profile of unsolvated Form 1 polymorph (all figures are in degrees 2Theta).
Preferably both features are exhibited.
The chemical name of the compound of formula (I) is 6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester.
The compound of formula (I) and compositions thereof have potentially beneficial anti-inflammatory or anti-allergic effects, particularly upon topical administration, demonstrated by, for example, its ability to bind to the glucocorticoid receptor and to illicit a response via that receptor, with long acting effect. Hence, the compound of formula (I) and compositions thereof is useful in the treatment of inflammatory and/or allergic disorders, especially in once-per-day therapy.
Space group P2 1 2 1 2 1 is characterised by angles of 90° being present in each of the 3 axes.
We have discovered that the compound of formula (I) can form a crystalline composition of characteristic space group, unit cell dimensions and crystalline structure as evidenced by X-ray diffraction with a very wide range of guest molecules.
The guest molecule preferably has a relative molecular weight in the range 16 to 150, more preferably 16 to 100, especially 40 to 100. Preferably the guest molecule is a liquid at ambient temperature and pressure (eg 295K, 1.013×10 5 Pa). However guest molecules which are a liquid under pressure may also be capable of acting as a guest molecule (especially under pressurised conditions). Substances which are solids at ambient temperature and pressure are also included.
The guest molecule preferably contains a moiety capable of acting as a hydrogen bond acceptor. Examples of moieties capable of acting as a hydrogen bond acceptor include carbonyl, sulphoxide, ether, —OH and amine groups (whether primary, secondary or tertiary amine groups) which moieties may form part of a carboxylic acid, ester or amide group. Moieties thioether and —SH may also be contemplated but are less preferred. Crystallographic studies have shown that a hydrogen bond acceptor on the guest is capable of interacting with the hydrogen atom of the C11 hydroxy on the compound of formula (I) thereby assisting the stabilisation of the crystal lattice (see in particular FIG. 2 A and FIG. 2 B). It is not ruled out that in some cases a hydrogen bond donor on the guest (eg the hydrogen atom of an —OH moiety) may be capable of interacting with the hydrogen bond acceptor on the compound of formula (I) thereby assisting the stabilisation of the crystal lattice.
Examples of suitable guest molecules include solvents e.g.:
amide moiety containing substances such as: dimethyl acetamide, dimethyl formamide, N-methyl-2-pyrrolidinone;
carbonyl moiety containing substances such as: acetone, methylethylketone, cyclopentanone;
sulphoxides such as dimethylsulphoxide;
alcohols such as: ethanol, butan-1-ol, propan-1-ol, propan-2-ol;
ethers such as: 1,4-dioxane, tetrahydrofuran;
esters such as: ethylformate, methylacetate;
carboxylic acids such as: acetic acid; water.
An example of a solid guest molecule is ε-caprolactam.
Preferred guest molecules are pharmaceutically acceptable substances and, as described below, compositions of the invention containing them may be used in therapy. However even if the guest molecule is not pharmaceutically acceptable then such compositions may be useful in the preparation of other compositions containing compound of formula (I), for example, other compositions of the invention containing guest molecules that are pharmaceutically acceptable or compound of formula (I) in unsolvated form.
In one sub-aspect of the invention, the composition is not an essentially stoichiometric composition containing as guest molecule one of the following:
acetone, dimethylformamide, dimethylacetamide, tetrahydrofuran, N-methyl-2-pyrrolidinone, propan-2-ol (isopropanol) or methylethylketone,
more particularly the composition is not a composition containing as guest molecule one of the aforementioned substances having stoichiometry of compound of formula (I) to solvent of 0.95-1.05:1.
In another sub-aspect of the invention, the composition is not a composition containing as guest molecule ethanol, water or methyl acetate, more particularly the composition is not an essentially stoichiometric composition containing as guest molecule one of the aforementioned substances, especially a composition having stoichiometry of compound of formula (I) to solvent of 0.95-1.05:1.
Preferred guest molecules include: cyclopentanone, dimethylsulfoxide, ethanol, propan-1-ol, butan-1-ol, 1,4-dioxane, ethyl formate, methyl acetate, water and acetic acid, particularly cyclopentanone, dimethylsulfoxide, propan-1-ol, 1,4-dioxane, ethyl formate, butan-1-ol and acetic acid.
The stoichiometry of the composition will usually be such that the ratio of compound to formula (I) to guest molecule, in molar terms, is 1:2.0-0.3, more preferably 1:1.6-0.6, especially 1: 1.2-0.8.
Unusually the composition of the invention has a crystal structure which is quite distinct from that of compound of formula (I) in the absence of a guest molecule, eg. the compound of formula (I) as unsolvated polymorph Form 1 which has a space group of P2 1 (i.e. two of the axis angles are 90°) and cell dimensions of 7.6, 14.1, 11.8 Å when determined at 150K. Thus if the guest molecule is removed below a threshold level (which will differ from guest to guest) for example by heating (optionally at reduced pressure eg under vacuum) then the crystal structure of the composition starts to break down and converts to that of the structure of an unsolvated compound of formula (I), typically unsolvated polymorph Form 1.
FIG. 3 shows the evolution of the XRPD profile of the composition with acetone when subjected to heating, and its in conversion to unsolvated polymorph Form 1.
The compositions with acetone, dimethylformamide, tetrahydrofuran. N-methyl-2-pyrrolidinone and acetic acid, at least, are particularly stable when subjected to heating, requiring a temperature in excess of 95° C. to cause substantial loss of guest from the crystal lattice. Of these, the compositions with acetone, dimethylformamide and acetic acid required a temperature in excess of 125° C. to cause substantial loss of guest.
Preferably the unit cell dimentions are about 12.1±0.6 Å, 14.9±0.7 Å, and 16.2±0.8 Å when determined at 120K. Usually the unit cell dimensions are about 12.1±0.4 Å, 14.9±0.6 Å, and 16.2±0.7 Å when determined at either 120K or 150K, especially when determined at 120K.
Table 1 shows the unit cell dimensions and peak positions for a number of example compositions:
TABLE 1
Guest molecule
Unit cell dimensions
Peak positions
Ethanol A
12.2
15.2
15.5
8.2
9.3
10.9
15.4
21.8
Propan-1-ol A
12.4
15.4
15.5
8.1
9.1
10.8
15.3
21.6
Propan-2-ol A
12.3
15.1
15.7
8.1
9.2
10.8
15.3
21.6
1,4-Dioxane A
12.5
14.6
16.1
8.2
9.3
10.8
15.1
21.6
Ethyl formate A
12.0
14.7
16.2
8.0
9.4
10.9
15.6
21.8
Acetic Acid A
11.9
14.5
16.1
8.2
9.5
11.0
15.7
21.7
Acetone A
11.9
14.7
16.2
8.1*
9.5
10.9
15.7
21.6
Dimethylformamide A
12.1
14.8
16.2
7.9
9.1
10.8
15.5
21.5
Dimethylacetamide A
12.2
14.9
16.6
8.0
9.4
10.8
15.4
21.6
Methylethylketone A
12.0
14.9
16.3
8.0
9.3
10.8
15.5
21.5
Tetrahydrofuran A
12.0
14.6
16.4
8.1
9.5
10.9
15.5
21.5
N-Methyl-2-pyrrolidinone B
12.0
14.9
16.8
7.9
9.4
10.8
15.5
21.6
N-Methyl-2-pyrrolidinone D
12.1
14.9
16.9
Dimethylsulphoxide
N/a
N/a
N/a
8.1*
9.4
10.9
15.4
21.5
Cyclopentanone
N/a
N/a
N/a
8.1
9.4
10.9
15.5
21.5
Water
N/a
N/a
N/a
8.1*
9.6
11.0
15.5
21.8
Butan-1-ol A
12.5
15.7
15.4
8.0
8.9
10.6
15.1
21.6
Methyl Acetate C
12.1
14.6
16.3
8.1
9.4
10.8
15.5
21.8
ε-caprolactam
N/a
N/a
N/a
8.1*
9.0
10.5
15.1
21.4
Superscripts refer to X-ray diffraction pattern collection conditions set out in the Examples section
N/a indicates data not available
*peak may not always be observed due to orientation effects
Compound (I) undergoes highly efficient hepatic metabolism to yield the 17-β carboxylic acid (X) as the sole major metabolite in rat and human in vitro systems. This metabolite has been synthesised and demonstrated to be >1000 fold less active than the parent compound in in vitro functional glucocorticoid assays.
This efficient hepatic metabolism is reflected by in vivo data in the rat, which have demonstrated plasma clearance at a rate approaching hepatic blood flow and an oral bioavailability of <1%, consistent with extensive first-pass metabolism.
In vitro metabolism studies in human hepatocytes have demonstrated that compound (I) is metabolised in an identical manner to fluticasone propionate but that conversion of (I) to the inactive acid metabolite occurs approximately 5-fold more rapidly than with fluticasone propionate. This very efficient hepatic inactivation would be expected to minimise systemic exposure in man leading to an improved safety profile.
Inhaled steroids are also absorbed through the lung and this route of absorption makes a significant contribution to systemic exposure. Reduced lung absorption could therefore provide an improved safety profile. Studies with compound (I) have shown significantly lower exposure to compound (I) than with fluticasone propionate after dry powder delivery to the lungs of anaesthetised pigs.
An improved safety profile is believed to allow the compound of formula (I) to demonstrate the desired anti-inflammatory effects when administered once-per day. Once-per-day dosing is considered to be significantly more convenient to patients than the twice-per day dosing regime that is normally employed for fluticasone propionate.
Examples of disease states in which the compound of formula (I) and compositions thereof have utility include skin diseases such as eczema, psoriasis, allergic dermatitis, neurodermatitis, pruritis and hypersensitivity reactions; inflammatory conditions of the nose, throat or lungs such as asthma (including allergen-induced asthmatic reactions), rhinitis (including hayfever), nasal polyps, chronic obstructive pulmonary disease, interstitial lung disease, and fibrosis; inflammatory bowel conditions such as ulcerative colitis and Crohn's disease; and auto-immune diseases such as rheumatoid arthritis.
The compound of formula (I) may also have use in the treatment of conjunctiva and conjunctivitis.
The composition of the invention is expected to be most useful in the treatment of inflammatory disorders of the respiratory tract e.g. asthma, COPD and rhinitis particularly asthma and rhinitis.
It will be appreciated by those skilled in the art that reference herein to treatment extends to prophylaxis as well as the treatment of established conditions.
As mentioned above, the composition of the invention is useful in human or veterinary medicine, in particular as an anti-inflammatory and anti-allergic agent.
There is thus provided as a further aspect of the invention the composition of the invention for use in human or veterinary medicine, particularly in the treatment of patients with inflammatory and/or allergic conditions, especially for treatment once-per-day.
According to another aspect of the invention, there is provided the use of the composition of the invention for the manufacture of a medicament for the treatment of patients with inflammatory and/or allergic conditions, especially for treatment once-per-day.
In a further or alternative aspect, there is provided a method for the treatment of a human or animal subject with an inflammatory and/or allergic condition, which method comprises administering to said human or animal subject an effective amount of the composition of the invention, especially for administration once-per-day.
The composition of the invention may be formulated for administration in any convenient way, and the invention therefore also includes within its scope pharmaceutical compositions comprising the composition of the invention together, if desirable, in admixture with one or more physiologically acceptable diluents or carriers. Pharmaceutical compositions suitable for once-per-day administration are of particular interest.
Further, there is provided a process for the preparation of such pharmaceutical compositions which comprises mixing the ingredients.
The composition of the invention may, for example, be formulated for oral, buccal, sublingual, parenteral, local or rectal administration, especially local administration.
Local administration as used herein, includes administration by insufflation and inhalation. Examples of various types of preparation for local administration include ointments, lotions, creams, gels, foams, preparations for delivery by transdermal patches, powders, sprays, aerosols, capsules or cartridges for use in an inhaler or insufflator or drops (e.g. eye or nose drops), solutions/suspensions for nebulisation, suppositories, pessaries, retention enemas and chewable or suckable tablets or pellets (e.g. for the treatment of aphthous ulcers) or liposome or microencapsulation preparations.
Advantageously compositions for topical administration to the lung include dry powder compositions and spray compositions.
Dry powder compositions for topical delivery to the lung by inhalation may, for example, be presented in capsules and cartridges for use in an inhaler or insufflator of, for example, gelatine. Formulations generally contain a powder mix for inhalation of the compound of the invention and a suitable powder base (carrier substance) such as lactose or starch. Use of lactose is preferred. Each capsule or cartridge may generally contain between 20 μg-10 mg of the compound of formula (I) in a composition of the invention optionally in combination with another therapeutically active ingredient. Alternatively, the composition of the invention may be presented without excipients. Packaging of the formulation may be suitable for unit dose or multi-dose delivery. In the case of multi-dose delivery, the formulation can be pre-metered (e.g. as in Diskus, see GB 2242134 or Diskhaler, see GB 2178965, 2129691 and 2169265) or metered in use (e.g. as in Turbuhaler, see EP 69715). An example of a unit-dose device is Rotahaler (see GB 2064336). The Diskus inhalation device comprises an elongate strip formed from a base sheet having a plurality of recesses spaced along its length and a lid sheet hermetically but peelably sealed thereto to define a plurality of containers, each container having therein an inhalable formulation containing a composition of the invention preferably combined with lactose. Preferably, the strip is sufficiently flexible to be wound into a roll. The lid sheet and base sheet will preferably have leading end portions which are not sealed to one another and at least one of the said leading end portions is constructed to be attached to a winding means. Also, preferably the hermetic seal between the base and lid sheets extends over their whole width. The lid sheet may preferably be peeled from the base sheet in a longitudinal direction from a first end of the said base sheet.
Pharmaceutical formulations which are non-pressurised and adapted to be administered as a dry powder topically to the lung via the buccal cavity (especially those which are free of excipient or are formulated with a diluent or carrier such as lactose or starch, most especially lactose) are of particular interest.
Spray compositions for topical delivery to the lung by inhalation may for example be formulated as aqueous solutions or suspensions or as aerosols delivered from pressurised packs, such as a metered dose inhaler, with the use of a suitable liquefied propellant. Aerosol compositions suitable for inhalation can be either a suspension or a solution and generally contain the composition of the invention optionally in combination with another therapeutically active ingredient and a suitable propellant such as a fluorocarbon or hydrogen-containing chlorofluorocarbon or mixtures thereof, particularly hydrofluoroalkanes, especially 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoro-n-propane or a mixture thereof. The aerosol composition may optionally contain additional formulation excipients well known in the art such as surfactants e.g. oleic acid or lecithin and cosolvents e.g. ethanol. One example formulation is excipient free and consists essentially of (e.g. consists of) composition of the invention (optionally together with a further active ingredient) and a propellant selected from 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoro-n-propane and mixture thereof. Another example formulation comprises particulate composition of the invention, a propellant selected from 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoro-n-propane and mixture thereof and a suspending agent which is soluble in the propellant e.g. an oligolactic acid or derivative thereof as described in WO94/21229. The preferred propellant is 1,1,1,2-tetrafluoroethane. Pressurised formulations will generally be retained in a canister (e.g. an aluminium canister) closed with a valve (e.g. a metering valve) and fitted into an actuator provided with a mouthpiece.
Medicaments for administration by inhalation desirably have a controlled particle size. The optimum particle size for inhalation into the bronchial system is usually 1-10 μm, preferably 2-5 μm. Particles having a size above 20 μm are generally too large when inhaled to reach the small airways. To achieve these particle sizes the particles of the composition of the invention as produced may be size reduced by conventional means e.g. by micronisation. The desired fraction may be separated out by air classification or sieving. Preferably, the particles will be crystalline, prepared for example by a process which comprises mixing in a continuous flow cell in the presence of ultrasonic radiation a flowing solution of compound of formula (I) as medicament in a liquid solvent with a flowing liquid antisolvent for said medicament (e.g. as described in International Patent Application PCT/GB99/04368) or else by a process which comprises admitting a stream of solution of the substance in a liquid solvent and a stream of liquid antisolvent for said substance tangentially into a cylindrical mixing chamber having an axial outlet port such that said streams are thereby intimately mixed through formation of a vortex and precipitation of crystalline particles of the substance is thereby caused (e.g. as described in International Patent Application PCT/GB00/04327).
When an excipient such as lactose is employed, generally, the particle size of the excipient will be much greater than the inhaled medicament within the present invention. When the excipient is lactose it will typically be present as milled lactose, wherein not more than 85% of lactose particles will have a MMD of 60-90 μm and not less than 15% will have a MMD of less than 15 μm.
Formulations for administration topically to the nose (e.g. for the treatment of rhinitis) include pressurised aerosol formulations and aqueous formulations administered to the nose by pressurised pump. Formulations which are non-pressurised and adapted to be administered topically to the nasal cavity are of particular interest. The formulation preferably contains water as the diluent or carrier for this purpose. Aqueous formulations for administration to the lung or nose may be provided with conventional excipients such as buffering agents, tonicity modifying agents and the like. Aqueous formulations may also be administered to the nose by nebulisation.
Other possible presentations include the following:
Ointments, creams and gels, may, for example, be formulated with an aqueous or oily base with the addition of suitable thickening and/or gelling agent and/or solvents.
Such bases may thus, for example, include water and/or an oil such as liquid paraffin or a vegetable oil such as arachis oil or castor oil, or a solvent such as polyethylene glycol. Thickening agents and gelling agents which may be used according to the nature of the base include soft paraffin, aluminium stearate, cetostearyl alcohol, polyethylene glycols, woolfat, beeswax, carboxypolymethylene and cellulose derivatives, and/or glyceryl monostearate and/or non-ionic emulsifying agents.
Lotions may be formulated with an aqueous or oily base and will in general also contain one or more emulsifying agents, stabilising agents, dispersing agents, suspending agents or thickening agents.
Powders for external application may be formed with the aid of any suitable powder base, for example, talc, lactose or starch. Drops may be formulated with an aqueous or non-aqueous base also comprising one or more dispersing agents, solubilising agents, suspending agents or preservatives.
If appropriate, the formulations of the invention may be buffered by the addition of suitable buffering agents.
The proportion of the active compound of formula (I) in the local compositions according to the invention depends on the precise type of formulation to be prepared but will generally be within the range of from 0.001 to 10% by weight. Generally, however for most types of preparations advantageously the proportion used will be within the range of from 0.005 to 1% and preferably 0.01 to 0.5%. However, in powders for inhalation or insufflation the proportion used will usually be within the range of from 0.1 to 5%.
Aerosol formulations are preferably arranged so that each metered dose or “puff” of aerosol contains 1 μg-2000 μg e.g. 20 μg-2000 μg, preferably about 20 μg-500 μg of compound of formula (I) optionally in combination with another therapeutically active ingredient. Administration may be once daily or several times daily, for example 2, 3, 4 or 8 times, giving for example 1, 2 or 3 doses each time. Preferably the composition of the invention is delivered once or twice daily. The overall daily dose with an aerosol will typically be within the range 10 μg-10 mg e.g. 100 μg-10 mg preferably, 200 μg-2000 μg.
Topical preparations may be administered by one or more applications per day to the affected area; over skin areas occlusive dressings may advantageously be used. Continuous or prolonged delivery may be achieved by an adhesive reservoir system.
For internal administration the compound according to the invention may, for example, be formulated in conventional manner for oral, parenteral or rectal administration. Formulations for oral administration include syrups, elixirs, powders, granules, tablets and capsules which typically contain conventional excipients such as binding agents, fillers, lubricants, disintegrants, wetting agents, suspending agents, emulsifying agents, preservatives, buffer salts, flavouring, colouring and/or sweetening agents as appropriate. Dosage unit forms are, however, preferred as described below.
Preferred forms of preparation for internal administration are dosage unit forms i.e. tablets and capsules. Such dosage unit forms contain from 0.1 mg to 20 mg preferably from 2.5 to 10 mg of the compound of formula (I).
The compound according to the invention may in general may be given by internal administration in cases where systemic adreno-cortical therapy is indicated.
In general terms preparations, for internal administration may contain from 0.05 to 10% of the active ingredient dependent upon the type of preparation involved. The daily dose may vary from 0.1 mg to 60 mg, e.g. 5-30 mg, dependent on the condition being treated, and the duration of treatment desired.
Slow release or enteric coated formulations may be advantageous, particularly for the treatment of inflammatory bowel disorders.
Since the compound of formula (I) is long-acting, preferably the composition of the invention will be delivered once-per-day and the dose will be selected so that the compound has a therapeutic effect in the treatment of respiratory disorders (e.g. asthma or COPD, particularly asthma) over 24 hours or more.
The pharmaceutical compositions according to the invention may also be used in combination with another therapeutically active agent, for example, a β 2 adrenoreceptor agonist, an anti-histamine or an anti-allergic. The invention thus provides, in a further aspect, a combination comprising the composition of the invention together with another therapeutically active agent, for example, a β 2 -adrenoreceptor agonist, an anti-histamine or an anti-allergic.
Examples of β 2 -adrenoreceptor agonists include salmeterol (e.g. as racemate or a single enantiomer such as the R-enantiomer), salbutamol, formoterol, salmefamol, fenoterol or terbutaline and salts thereof, for example the xinafoate salt of salmeterol, the sulphate salt or free base of salbutamol or the fumarate salt of formoterol. Pharmaceutical compositions employing combinations with long-acting β 2 -adrenoreceptor agonists (e.g. salmeterol and salts thereof) are particularly preferred, especially those which have a therapeutic effect (e.g. in the treatment of asthma or COPD, particularly asthma) over 24 hours or more.
Since the compound of formula (I) is long-acting, preferably the composition comprising the compound of formula (I) and the long-acting β 2 -adrenoreceptor agonists will be delivered once-per-day and the dose of each will be selected so that the composition has a therapeutic effect in the treatment of respiratory disorders effect (e.g. in the treatment of asthma or COPD, particularly asthma, over 24 hours or more.
Examples of anti-histamines include methapyrilene or loratadine.
Other suitable combinations include, for example, other anti-inflammatory agents e.g. NSAIDs (e.g. sodium cromoglycate, nedocromil sodium, PDE4 inhibitors, leukotriene antagonists, iNOS inhibitors, tryptase and elastase inhibitors, beta-2 integrin antagonists and adenosine 2a agonists)) or antiinfective agents (e.g. antibiotics, antivirals).
Also of particular interest is use of the composition of the invention in combination with a phosphodiesterase 4 (PDE4) inhibitor e.g. cilomilast or a salt thereof.
The combination referred to above may conveniently be presented for use in the form of a pharmaceutical formulation and thus pharmaceutical formulations comprising a combination as defined above together with a physiologically acceptable diluent or carrier represent a further aspect of the invention.
The compound according to the invention in combination with another therapeutically active ingredient as described above may be formulated for administration in any convenient way, and the invention therefore also includes within its scope pharmaceutical formulations comprising the composition of the invention in combination with another therapeutically active ingredient together, if desirable, in admixture with one or more physiologically acceptable diluents or carriers. The preferred route of administration for inflammatory disorders of the respiratory tract will generally be administration by inhalation.
Further, there is provided a process for the preparation of such pharmaceutical compositions which comprises mixing the ingredients.
Therapeutic agent combinations may be in any form, for example combinations may comprise a single dose containing separate particles of individual therapeutics, and optionally excipient material(s), alternatively, multiple therapeutics may be formed into individual multicomponent particles, formed for example by coprecipitation, and optionally containing excipient material(s).
The individual compounds of such combinations may be administered either sequentially in separate pharmaceutical compositions as well as simultaneously in combined pharmaceutical formulations. Appropriate doses of known therapeutic agents will be readily appreciated by those skilled in the art.
The composition of the invention may be prepared by the methodology described hereinafter, constituting a further aspect of this invention.
A first process for preparing a composition of the invention comprises crystallising the composition from a solution containing a compound of formula (I) and the guest molecule. The solution containing the guest molecule could be the guest itself when this a liquid, or could be the guest dissolved in another liquid substance which substance does not act as a guest molecule.
Optionally, for better control and reproduceability, the crystallisation process may be assisted by seeding with crystals of the composition of the invention. The seed crystals of the composition of the invention need not contain the same guest molecule.
A second process for preparing a composition of the invention comprises contacting the compound of formula (I) or a composition according to the invention thereof in solid form with a liquid containing the guest molecule (for example by slurrying) and obtaining the composition therefrom. The liquid containing the guest molecule could be the guest itself when this a liquid, or could be the guest dissolved in another liquid substance which substance does not act as a guest molecule.
A third process for preparing a composition of the invention comprises contacting a compound of formula (I) or a composition according to the invention thereof in solid form with a vapour containing the guest molecule. This process is suitable when the guest has acceptable volatility e.g. when the guest is a solvent.
In the second and third processes, the compound of formula (I) may be employed in the form of a composition with a guest molecule or in a form without a guest molecule (eg as unsolvated polymorph Form 1, 2 or 3). In the first process the compound of formula (I) or a composition according to the invention may be dissolved in the solution or prepared in situ.
In one particular embodiment of this aspect of the invention the input compound of formula (I) in the first, second and third processes is in the form of a substantially amorphous solid. Preferably the compound of formula (I) in the form of a substantially amorphous solid is preferably in the form of substantially amorphous particles. For example the the compound of formula (I) in the form of substantially amorphous particles may be obtained by spray drying a solution containing the compound of formula (I). Any solvent that will dissolve the compound of formula (I) that can be evaporated safely in a spray drying process may be used. Suitable solvents for forming the solution include, but are not limited to, methyl acetate, ethyl acetate, isopropyl acetate, acetone, 2-butanone, 3-pentanone, 4-methyl-2-pentanone, ethanol, methanol, 1-propanol, propan-2-ol, acetonitrile, chloroform, dichloromethane especially methylethylketone (2-butanone). Solution concentration will typically be 0.5-50% specifically 10-40% eg 20-30%. Lower concentrations may be more suitable for preparing smaller particle sizes especially 2-4% e.g. 3.5-4%. The concentration that may be employed will be limited by the dissolution power of the solvent. Methylethylketone is preferred since it dissolves compound of formula (I) at a relatively high concentration which results in production advantages. The compound of formula (I) may be employed in non-solvated form or in the form of a composition of the invention (e.g. with acetone). Preferably it is employed as the non-solvated Form 1 polymorph. Spray drying maybe performed, for example, using apparatus supplied by Buchi or Niro. A pneumatic spray nozzle orifice of e.g. 0.04 inches is suitable, although alternate atomization methods such as rotary and pressure nozzles can be used. Solution flow rate may typically be in the range 1-100 ml/min, especially 15-30 ml/min. The inlet temperature and flow rate combination should be suitable to evaporate the solvent completely to minimize the risk of solvent trapped in the particle expediting an amorphous to crystalline transition. Inlet temperatures can range from 50-250° C., typically 100-200° C.
Compound of formula (I) in unsolvated form which is itself a useful substance has been found to exist in 3 crystalline polymorphic forms, Forms 1, 2 and 3, although Form 3 may be an unstable variant of Form 2. The Forms are characterised by their XRPD patterns shown in FIG. 5 . Broadly speaking the Forms are characterised in their XRPD profiles as follows:
Form 1: Peak at around 18.9 degrees 2Theta
Form 2: Peaks at around 18.4 amd 21.5 degrees 2Theta
Form 3: Peaks at around 18.6 and 19.2 degrees 2Theta.
Forms 1 appears likely to be the thermodynamically most stable form since Forms 2 and 3 are converted into Form 1 on heating.
A process for preparing a compound of formula (I) as crystalline unsolvated Form 1 polymorph comprises dissolving compound of formula (I) in methylisobutylketone or ethyl acetate and producing compound of formula (I) as unsolvated Form 1 by addition of an anti-solvent such as iso-octane or toluene.
According to a first preferred embodiment of this process the compound of formula (I) may be dissolved in ethyl acetate and compound of formula (I) as unsolvated Form 1 polymorph may be obtained by addition of toluene as anti-solvent. In order to improve the yield, preferably the ethyl acetate solution is hot and once the toluene has been added the mixture is distilled to reduce the content of ethyl acetate.
According to a second preferred embodiment of this process the compound of formula (I) may be dissolved in methylisobutylketone and compound of formula (I) as crystalline unsolvated Form 1 polymorph may be obtained by addition of isooctane as anti-solvent.
A process for preparing a compound of formula (I) as unsolvated Form 2 polymorph comprises dissolving compound of formula (I) in unsolvated form in methanol or dry dichloromethane and recrystallising the compound of formula (I) as unsolvated Form 2 polymorph. Typically the compound of formula (I) will be dissolved in hot in methanol or dry dichloromethane and allowed to cool.
A process for preparing a preparing a compound of formula (I) as unsolvated Form 3 polymorph comprises dissolving compound of formula (I) in particular as the composition with acetone in dichloromethane in the presence of water (typically 1-3% water by volume) and recrystallising the compound of formula (I) as unsolvated Form 3 polymorph.
As mentioned above, compositions of the invention may also find use as manufacturing intermediates in the preparation of compound of formula (I) in unsolvated form, or in the preparation of other compositions of the invention, or in pharmaceutical compositions thereof.
For example, a process for preparation of compound of formula (I) in unsolvated form (typically unsolvated polymorph Form 1) comprises removing the guest molecule from a composition of the invention.
The methodology described herein for preparing compositions of the invention may also be useful in preparing compositions of the invention of defined crystal habit and also for preparing compounds of formula (I) in unsolvated form (typically unsolvated polymorph Form 1) of defined crystal habit. In particular the compositions of the invention with acetone are particularly advantageous since when prepared according to the method substantially as described in Example 1, second alternative method they are produced in the form of equant or substantially equant particles (typically elongated tetragonal bipyramidal crystals) which are readily micronised with high efficiency. The compositions of the invention with propan-2-ol are also particularly advantageous since when prepared according to the method substantially as described in Example 3, second alternative method they are produced in the form of equant or substantially equant particles (typically tetragonal bipyramidal crystals) which are also readily micronised with high efficiency. If these compositions of the invention are converted to unsolvated form (typically unsolvated Form 1) by removal of the guest molecule (eg on heating, typically to around 100-110 eg 105° C.) then the unsolvated form is prepared in the corresponding advantageous crystal habit. Unsolvated polymorph Form 1 when prepared by this method either from compositions of the invention with a acetone or compositions of the invention with propan-2-ol are much more readily micronised than the needle shaped crystals prepared by the method described above involving recrystallisation from ethylacetate and toluene. The different shaped particles are shown in FIGS. 6 to 8 .
Equant and substantially equant particles may be single crystals or agglomerations of crystals. Equant particles have dimensions in each of the three axes of measurement which are approximately the same, for example they have dimensions in the three axes such that the difference between the largest and the smallest measurement is not more than approximately 50% of the smallest. Particles which are single crystals are typically equant. Particles which are agglomerations of crystals are typically substantially equant such that the particles have dimensions in the three axes such that the difference between the largest and the smallest measurement is not more than approximately 100% of the smallest, particularly not more than 50% of the smallest.
Thus according to another aspect of the invention we provide a process for preparing compound of formula (I) in unsolvated form (typically unsolvated Form 1) in the form of equant or substantially equant particles by a process comprising:
(a) preparing a composition of the invention in the form of equant or substantially equant particles; and
(b) removing the guest molecule eg by heating.
In step (a) preferably the composition is a composition with propan-2-ol or acetone as guest molecule.
We also claim compound of formula (I) in unsolvated form (typically unsolvated Form 1) in the form of equant or substantially equant particles eg obtainable by such a process.
We also claim a composition according to the invention in the form of equant or substantially equant particles, especially a composition with acetone or propan-2-ol.
A process for preparing a compound of formula (I) comprises alkylation of a thioacid of formula (II)
or a salt thereof.
In this process the compound of formula (II) may be reacted with a compound of formula FCH 2 L wherein L represents a leaving group (e.g. a halogen atom, a mesyl or tosyl group or the like) for example, an appropriate fluoromethyl halide under standard conditions. Preferably, the fluoromethyl halide reagent is bromofluoromethane. Preferably the compound of formula (II) is employed as a salt, particularly the salt with diisopropylethylamine.
In a preferred process for preparing the compound of formula (I), the compound of formula (II) or a salt thereof is treated with bromofluoromethane optionally in the presence of a phase transfer catalyst. A preferred solvent is methylacetate, or more preferably ethylacetate, optionally in the presence of water. The presence of water improves solubility of both starting material and product and the use of a phase transfer catalyst results in an increased rate of reaction. Examples of phase transfer catalysts that may be employed include (but are not restricted to) tetrabutylammonium bromide, tetrabutylammonium chloride, benzyltributylammonium bromide, benzyltributylammonium chloride, benzyltriethylammonium bromide, methyltributylammonium chloride and methyltrioctylammonium chloride. THF has also successfully been employed as solvent for the reaction wherein the presence of a phase transfer catalyst again provides a significantly faster reaction rate. Preferably the product present in an organic phase is washed firstly with aqueous acid e.g. dilute HCl in order to remove amine compounds such as triethylamine and diisopropylethylamine and then with aqueous base e.g. sodium bicarbonate in order to remove any unreacted precursor compound of formula (II).
Compounds of formula (II) may be prepared from the corresponding 17α-hydroxyl derivative of formula (III):
using for example, the methodology described by G. H. Phillipps et al., (1994) Journal of Medicinal Chemistry, 37, 3717-3729. For example the step typically comprises the addition of a reagent suitable for performing the esterification e.g. an activated derivative of 2-furoic acid such as an activated ester or preferably a 2-furoyl halide e.g. 2-furoyl chloride (employed in at least 2 times molar quantity relative to the compound of formula (III)) in the presence of an organic base e.g. triethylamine. The second mole of 2-furoyl chloride reacts with the thioacid moiety in the compound of formula (III) and needs to be removed e.g. by reaction with an amine such as diethylamine.
This method suffers disadvantages, however, in that the resultant compound of formula (II) is not readily purified of contamination with the by-product 2-furoyldiethylamide. We have therefore invented several improved processes for performing this conversion.
In a first such improved process we have discovered that by using a more polar amine such as diethanolamine, a more water soluble by-product is obtained (in this case 2-furoyldiethanolamide) which permits compound of formula (II) or a salt thereof to be produced in high purity since the by-product can efficiently be removed by water washing.
Thus we provide a process for preparing a compound of formula (II) which comprises:
(a) reacting a compound of formula (III) with an activated derivative of 2-furoic acid as in an amount of at least 2 moles of the activated derivative per mole of compound of formula (III) to yield a compound of formula (IIA)
; and
(b) removal of the sulphur-linked 2-furoyl moiety from compound of formula (IIA) by reaction of the product of step (a) with an organic primary or secondary amine base capable of forming a water soluble 2-furoyl amide.
In two particularly convenient embodiments of this process we also provide methods for the efficient purification of the end product which comprise either
(c1) when the product of step (b) is dissolved in a substantially water immiscible organic solvent, purifying the compound of formula (II) by washing out the amide by-product from step (b) with an aqueous wash, or
(c2) when the product of step (b) is dissolved in a water miscible solvent, purifying the compound of formula (II) by treating the product of step (b) with an aqueous medium so as to precipitate out pure compound of formula (II) or a salt thereof.
In step (a) preferably the activated derivative of 2-furoic acid may be an activated ester of 2-furoic acid, but is more preferably a 2-furoyl halide, especially 2-furoyl chloride. A suitable solvent for this reaction is ethylacetate or methylacetate (preferably methylacetate) (when step (c1) may be followed) or acetone (when step (c2) may be followed). Normally an organic base e.g. triethylamine will be present. In step (b) preferably the organic base is diethanolamine. The base may suitably be dissolved in a solvent e.g. methanol. Generally steps (a) and (b) will be performed at reduced temperature e.g. between 0 and 5° C. In step (c1) the aqueous wash may be water, however the use of brine results in higher yields and is therefore preferred. In step (c2) the aqueous medium is for example a dilute aqueous acid such as dilute HCl.
We also provide an alternative process for preparing a compound of formula (II) which comprises:
(a) reacting a compound of formula (III) with an activated derivative of 2-furoic acid in an amount of at least 2 moles of activated derivative per mole of compound of formula (III) to yield a compound of formula (IIA); and
(b) removal of the sulphur-linked 2-furoyl moiety from compound of formula (IIA) by reaction of the product of step (a) with a further mole of compound of formula (III) to give two moles of compound of formula (II).
In step (a) preferably the activated derivative of 2-furoic acid may be an activated ester of 2-furoic acid, but is more preferably a 2-furoyl halide, especially 2-furoyl chloride. A suitable solvent for his step is acetone. Normally an organic base e.g. triethylamine will be present. In step (b) a suitable solvent is DMF or dimethylacetamide. Normally an organic base e.g. triethylamine will be present. Generally steps (a) and (b) will be performed at reduced temperature e.g. between 0 and 5° C. The product may be isolated by treatment with acid and washing with water.
This aforementioned process is very efficient in that it does not produce any furoylamide by-product (thus affording inter alia environmental advantages) since the excess mole of furoyl moiety is taken up by reaction with a further mole of compound of formula (II) to form an additional mole of compound of formula (II).
Further general conditions for the conversion of compound of formula (III) to compound of formula (II) in the two processes just described will be well known to persons skilled in the art.
According to a preferred set of conditions, however, we have found that the compound of formula (II) may advantageously be isolated in the form of a solid crystalline salt. The preferred salt is a salt formed with a base such as triethylamine, 2,4,6-trimethylpyridine, diisopropylethylamine or N-ethylpiperidine. Such salt forms of compound of formula (II) are more stable, more readily filtered and dried and can be isolated in higher purity than the free thioacid. The most preferred salt is the salt formed with diisopropylethylamine. The triethylamine salt is also of interest.
Compounds of formula (III) may be prepared in accordance with procedures described in GB 2088877B.
Compounds of formula (III) may also be prepared by a process comprising the following steps:
Step (a) comprises oxidation of a solution containing the compound of formula (V). Preferably, step (a) will be performed in the presence of a solvent comprising methanol, water, tetrahydrofuran, dioxan or diethylene glygol dimethylether. So as to enhance yield and throughput, preferred solvents are methanol, water or tetrahydrofuran, and more preferably are water or tetrahydrofuran, especially water and tetrahydrofuran as solvent. Dioxan and diethylene glygol dimethylether are also preferred solvents which may optionally (and preferably) be employed together with water. Preferably, the solvent will be present in an amount of between 3 and 10 vol relative to the amount of the starting material (1 wt.), more preferably between 4 and 6 vol., especially 5 vol. Preferably the oxidising agent is present in an amount of 1-9 molar equivalents relative to the amount of the starting material. For example, when a 50% w/w aqueous solution of periodic acid is employed, the oxidising agent may be present in an amount of between 1.1 and 10 wt. relative to the amount of the starting material (1 wt.), more preferably between 1.1 and 3 wt., especially 1.3 wt. Preferably, the oxidation step will comprise the use of a chemical oxidising agent. More preferably, the oxidising agent will be periodic acid or iodic acid or a salt thereof. Most preferably, the oxidising agent will be periodic acid or sodium periodate, especially periodic acid. Alternatively (or in addition), it will also be appreciated that the oxidation step may comprise any suitable oxidation reaction, e.g. one which utilises air and/or oxygen. When the oxidation reaction utilises air and/or oxygen, the solvent used in said reaction will preferably be methanol. Preferably, step (a) will involve incubating the reagents at room temperature or a little warmer, say around 25° C. e.g. for 2 hours. The compound of formula (IV) may be isolated by recrystallisation from the reaction mixture by addition of an anti-solvent. A suitable anti-solvent for compound of formula (IV) is water. Surprisingly we have discovered that it is highly desirable to control the conditions under which the compound of formula (IV) is precipitated by addition of anti-solvent e.g. water. When the recrystallisation is performed using chilled water (e.g. water/ice mixture at a temperature of 0-5° C.) although better anti-solvent properties may be expected we have found that the crystalline product produced is very voluminous, resembles a soft gel and is very difficult to filter. Without being limited by theory we believe that this low density product contains a large amount of solvated solvent within the crystal lattice. By contrast when conditions of around 10° C. or higher are used (e.g. around ambient temperature) a granular product of a sand like consistency which is very easily filtered is produced. Under these conditions, crystallisation typically commences after around 1 hour and is typically completed within a few hours (e.g. 2 hours). Without being limited by theory we believe that this granular product contains little or no solvated solvent within the crystal lattice.
Step (b) will typically comprise the addition of a reagent suitable for converting a carboxylic acid to a carbothioic acid e.g. using hydrogen sulphide gas together with a suitable coupling agent e.g. carbonyldiimidazole (CDI) in the presence of a suitable solvent e.g. dimethylformamide.
The advantages of the composition comprising a compound of formula (I) together with a guest compound according to the invention may include the fact that the substance appears to demonstrate excellent anti-inflammatory properties, with predictable pharmacokinetic and pharmacodynamic behaviour, with an attractive side-effect profile, long duration of action, and is compatible with a convenient regime of treatment in human patients, in particular being amenable to once-per day dosing. Further advantages may include the fact that the substance has desirable physical and chemical properties which allow for ready manufacture and storage. Alternatively it may serve as a useful intermediate in the preparation of other forms of the compound of formula (I) or compositions thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 : Figure showing the spacial arrangement of 4 steroid and 4 guest molecules in the unit cell of compositions of the invention with THF (upper figure) and DMF (lower figure) (guest molecule darkened).
FIG. 2 A: Figure showing detail of the spacial arrangement of steroid and guest molecules in compositions of the invention with THF.
FIG. 2 B: Figure showing detail of the spacial arrangement of steroid and guest molecules in compositions of the invention with DMF.
FIG. 3 : Figure showing the evolution of the XRPD profile of the composition of the invention with acetone on heating, in particular showing its conversion to compound of formula (I) as unsolvated Form 1
FIG. 4 : XRPD profiles for a range of compositions according to the invention (refer to Table 1)
FIG. 5 : Comparison of XRPD profiles of Form 1, Form 2 and Form 3 polymorphs of unsolvated compound of formula (I).
FIG. 6 : Scanning Electron Microscopy (SEM) study of crystals of unsolvated polymorph Form 1.
FIG. 7 : Scanning Electron Microscopy (SEM) study of crystals of compositions of the invention with acetone
FIG. 8 : Scanning Electron Microscopy (SEM) study of crystals of compositions of the invention with propan-2-ol.
FIG. 9 : Raman spectrum of composition of the invention with butan-1-ol
FIG. 10 : Raman spectrum of composition of the invention with methyl acetate
FIG. 11 : Raman spectrum of composition of the invention with acetic acid
FIG. 12 : Raman spectrum of composition of the invention with propan-1-ol
FIG. 13 : Raman spectrum of composition of the invention with ethanol
FIG. 14 : Raman spectrum of composition of the invention with ethyl formate
FIG. 15 : Raman spectrum of composition of the invention with 1,4-dioxane
FIG. 16 : Raman spectrum of composition of the invention with dimethylsulphoxide
FIG. 17 : Enlarged XRPD profile of composition of the invention with acetone
FIG. 18 : Enlarged XRPD profile of composition of the invention with methylethylketone
FIG. 19 : Enlarged XRPD profile of composition of the invention with propan-2-ol
FIG. 20 : Enlarged XRPD profile of composition of the invention with tetrahydrofuran
FIG. 21 : Enlarged XRPD profile of composition of the invention with dimethylformamide
FIG. 22 : Enlarged XRPD profile of composition of the invention with butan-1-ol
FIG. 23 : Enlarged XRPD profile of composition of the invention with methyl acetate
FIG. 24 : Enlarged XRPD profile of composition of the invention with acetic acid
FIG. 25 : Enlarged XRPD profile of composition of the invention with propan-1-ol
FIG. 26 : Enlarged XRPD profile of composition of the invention with ethanol
FIG. 27 : Enlarged XRPD profile of composition of the invention with ethyl formate
FIG. 28 : Enlarged XRPD profile of composition of the invention with 1,4-dioxane
FIG. 29 : Enlarged XRPD profile of composition of the invention with dimethylsulphoxide
FIG. 30 : Enlarged XRPD profile of composition of the invention with N-methyl-2-pyrrolidinone
FIG. 31 : Enlarged XRPD profile of composition of the invention with dimethylacetamide
FIG. 32 : Enlarged XRPD profile of composition of the invention with water
FIG. 33 : Enlarged XRPD profile of composition of the invention with cyclopentanone
FIG. 34 : Enlarged XRPD profile of composition of the inventoin with ε-caprolactam.
The following non-limiting Examples illustrate the invention:
EXAMPLES
General
1 H-nmr spectra were recorded at 400 MHz and the chemical shifts are expressed in ppm relative to tetramethylsilane. The following abbreviations are used to describe the multiplicities of the signals: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), dd (doublet of doublets), ddd (doublet of doublet of doublets), dt (doublet of triplets) and b (broad). Biotage refers to prepacked silica gel cartridges containing KP-Sil run on flash 12i chromatography module. LCMS was conducted on a Supelcosil LCABZ+PLUS column (3.3 cm×4.6 mm ID) eluting with 0.1% HCO 2 H and 0.01 M ammonium acetate in water (solvent A), and 0.05% HCO 2 H 5% water in acetonitrile (solvent B), using the following elution gradient 0-0.7 min 0%B, 0.7-4.2 min 100%B, 4.2-5.3 min 0%B, 5.3-5.5 min 0%B at a flow rate of 3 ml/min. The mass spectra were recorded on a Fisons VG Platform spectrometer using electrospray positive and negative mode (ES+ve and ES−ve).
The XRPD analyses shown in the figures were performed on either
a) a Phillips X'pert MPD powder diffractometer, serial number DY667. The pattern was recorded using the following acquisition conditions: Tube anode: Cu, Start angle: 2.0°2θ, End angle: 45.0°2θ, Step size: 0.02°2θ, Time per step: 1 second. XRPD profiles were collected at ambient temperature (295K) unless otherwise indicated, or
b) a Philips PW1710 powder diffractometer. The pattern was recorded using the following acquisition conditions: Tube anode: Cu, Start angle: 3.5°2θ, End angle: 35.0°2θ, Step size: 0.02°2θ, Time per step: 2.3 seconds. XRPD profiles were collected at ambient temperature (295K).
The diffractometer used in each case can be determined by the end angle in the figure.
Raman spectra were recorded with the sample in an NMR tube using a Nicolet 960 E.S.P. FT-Raman spectrometer, at 4 cm-1 resolution with excitation from a Nd:V04 laser (1064 nm) with a power output of 400 mW.
X-ray diffraction pattern collections referred to in Table 1 were performed in the following manners:
A=The crystal and molecular structures and corresponding unit cell dimensions were determined from three-dimensional X-ray diffraction data collected at 120+/−2 K. All measurements were made using a Bruker SMART CCD diffractometer with graphite monochromated Mo-Kα radiation (λ=0.71073 Å) from a fine focus sealed tube source. The structure was solved by direct methods and refined using full-matrix least-squares procedures which minimized the function Sw(Fo 2 −Fc 2 ) 2 . The Bruker SHELX software was used throughout.
B=The crystal and molecular structures and corresponding unit cell dimensions were determined from three-dimensional X-ray diffraction data collected at 150+/−2 K. All measurements were made using a KappaCCD diffractometer with graphite monochromated Mo-Kα radiation (λ=0.71073 Å) from a fine focus sealed tube source. The structure was solved by direct methods and refined using full-matrix least-squares procedures which minimized the function Sw(Fo 2 −Fc 2 ) 2 . The Bruker AXS SHELXTL software package (Ver. 5.10, UNIX) was used throughout.
C=The crystal and molecular structures and corresponding unit cell dimensions were determined from three-dimensional X-ray diffraction data collected at 150+/−2 K. All measurements were made using a Bruker AXS SMART 6000 diffractometer with graphite monochromated Cu-Kα radiation (λ=1.54178 Å) from a normal focus sealed tube source. The structure was solved by direct methods and refined using full-matrix least-squares procedures which minimized the function Sw(Fo 2 −Fc 2 ) 2 . The Bruker AXS SHELXTL software package (Ver. 5.10, UNIX) was used throughout.
D=as B but with collection at temperature of 295K.
The Scanning Electron Microscopy (SEM) was carried out on a Philips XL30 Scanning Electron Microscope serial number D814. An acceleration voltage in the range 20 to 25 kV was used to give magnifications in the range of 30 to 600×. Images were captured digitally using a CCD detector.
Intermediates
Intermediate 1: 6α,9α-Difluoro-17α[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid Diisopropylethylamine Salt
A stirred suspension of 6α,9α-difluoro-11β,17α-dihydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid (prepared in accordance with the procedure described in GB 2088877B) (49.5 g) in methylacetate (500 ml) is treated with triethylamine (35 ml) maintaining a reaction temperature in the range 0-5° C. 2-Furoyl chloride (25 ml) is added and the mixture stirred at 0-5° C. for 1 hour. A solution of diethanolamine (52.8 g) in methanol (50 ml) is added and the mixture stirred at 0-5° C. for at least 2 hours. Dilute hydrochloric acid (approx 1 M, 550 ml) is added maintaining a reaction temperature below 15° C. and the mixture stirred at 15° C. The organic phase is separated and the aqueous phase is back extracted with methyl acetate (2×250 ml). All of the organic phases are combined, washed sequentially with brine (5×250 ml) and treated with di-isopropylethylamine (30 ml). The reaction mixture is concentrated by distillation at atmospheric pressure to an approximate volume of 250 ml and cooled to 25-30° C. (crystallisation of the desired product normally occurs during distillation/subsequent cooling). Tertiary butyl methyl ether (TBME) (500 ml) is added, the slurry further cooled and aged at 0-5° C. for at least 10 minutes. The product is filtered off, washed with chilled TBME (2×200 ml) and dried under vacuum at approximately 40-50° C. (75.3 g, 98.7%). NMR (CDCl 3 ) δ: 7.54-7.46 (1H, m), 7.20-7.12 (1H, dd), 7.07-6.99 (1H, dd), 6.48-6.41 (2H, m), 6.41-6.32 (1H, dd), 5.51-5.28 (1H, dddd 2 J H-F 50 Hz), 4.45-4.33(1H, bd), 3.92-3.73 (3H, bm), 3.27-3.14 (2H, q), 2.64-2.12 (5H, m), 1.88-1.71 (2H, m), 1.58-1.15 (3H, s), 1.50-1.38 (15H, m), 1.32-1.23 (1H, m), 1.23-1.15 (3H s), 1.09-0.99 (3H, d)
Intermediate 2: 6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Unsolvated Form 1
A mobile suspension of Intermediate 1 (12.61 g, 19.8 mmol) in ethyl acetate (230 ml) and water (50 ml) is treated with a phase transfer catalyst (benzyltributylammonium chloride, 10 mol %), cooled to 3° C. and treated with bromofluoromethane (1.10 ml, 19.5 mmol, 0.98 equivalents), washing in with prechilled (0° C.) ethyl acetate (EtOAc) (20 ml). The suspension is stirred overnight, allowing to warm to 17° C. The aqueous layer is separated and the organic phase is sequentially washed with 1 M HCl (50 ml), 1%w/v NaHCO 3 solution (3×50 ml) and water (2×50 ml). The ethylacetate solution is distilled at atmospheric pressure until the distillate reaches a temperature of approximately 73° C. at which point toluene (150 ml) is added. Distillation is continued at atmospheric pressure until all remaining EtOAc has been removed (approximate distillate temperature 103° C.). The resultant suspension is cooled and aged at <10° C. and filtered off. The bed is washed with toluene (2×30 ml) and the product oven dried under vacuum at 60° C. to constant weight to yield the title compound (8.77 g, 82%) LCMS retention time 3.66 min, m/z 539 MH + , NMR δ(CDCl 3 ) includes 7.60 (1H, m), 7.18-7.11 (2H, m), 6.52 (1H, dd, J=4.2 Hz), 6.46 (1H, s), 6.41 (1H, dd, J 10, 2 Hz), 5.95 and 5.82 (2H dd, J 51, 9 Hz), 5.48 and 5.35 (1H, 2m), 4.48 (1H, m), 3.48 (1H, m), 1.55 (3H, s), 1.16 (3H, s), 1.06 (3H, d, J7 Hz).
Intermediate 3: 6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid
A stirred suspension of 6α, 9α-difluoro-11β,17α-dihydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid (prepared in accordance with the procedure described in GB 2088877B) (1 wt, 49.5 g) in acetone (10 vol) is cooled to 0-5° C. and treated with triethylamine (0.51 wt, 2.1 eq), keeping the temperature below 5° C., and stirred for 5 min at 0-5°. 2-Furoyl chloride (0.65 wt, 2.05 eq) is then added over a minimum of 20 min, maintaining a reaction temperature at 0-5° C. The reaction mixture is stirred for at least 30 minutes and diluted with water (10 vol) maintaining a reaction temperature in the range 0-5° C. The resultant precipitate is collected by filtration and washed sequentially with acetone/water (50/50 2 vol) and water (2×2 vol). The product is dried under vacuum at approximately 55° C. overnight to leave 6α,9α-difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-yl S-(2-furanylcarbonyl)thioanhydride as a white solid (70.8 g, 98.2%) (NMR δ(CD 3 CN) 0.99 (3H, d) (J=7.3 Hz), 1.24 (3H, s), 1.38 (1H, m) (J=3.9 Hz) 1.54 (3H, s), 1.67 (1H, m), 1.89 (1H, broad d) (J=15.2 Hz), 1.9-2.0 (1H, m), 2.29-2.45 (3H, m), 3.39 (1H, m), 4.33 (1H, m), 4.93 (1H, broad s), 5.53 (1H, ddd) (J=6.9, 1.9 Hz; J HF =50.9 Hz), 6.24 (1H, m), 6.29 (1H, dd) (J=10.3, 2.0 Hz), 6.63 (2H, m), 7.24-7.31 (3H, m), 7.79 (1H, dd) (J=<1 Hz), 7.86 (1H, dd) (J=<1 Hz)). A portion of the product (0.56 g) is mixed with 6α,9α-difluoro-11β, 17α-dihydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid (0.41 g) in a 1:1 molar ratio in DMF (10 volumes wrt total steroid input). The reaction mixture is treated with triethylamine (approximately 2.1 equivalents) and the mixture is stirred at approximately 20° C. for approximately 6 hours. Water (50 vol) containing excess conc HCl (0.5 vol) is added to the reaction mixture and the resultant precipitate collected by filtration. The bed is washed with water (2×5 vol) and dried in vacuo at approximately 55° C. overnight to leave the title compound as a white solid (0.99 g, 102%).
Intermediate 4A: 6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester, Amorphous Particles
Intermediate 2 (30.04 g) was dissolved in methylethylketone (850 ml) to give a 3.5% solution. The solution was spray dried using a Niro Mobile Minor spray drier (Niro Inc, Columbia, Md., USA). The spray orifice was a two fluid pneumatic nozzle with 0.04 inch orifice diameter (Spray Systems Co, Wheaton, Ill., USA). The other spray drying parameters were as follows:
Temperature: 150° C., outlet temperature 98° C.
Solution flow rate: 30 ml/min using Isco 260D syringe pump (Isco Inc, Lincoln, Nebr., USA)
Atomisation Pressure: 2 Bar
Particle collection was achieved in the conventional manner using a Fisher Klosterman XQ120-1.375 high efficiency cyclone (Fisher-Klosterman Inc, Louisville, Ky., USA). A white powder was recovered. The spray drying process was successful at producing smooth, spherical particles of amorphous 6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester. System yield was 61%
Intermediate 4B: 6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester, Amorphous Particles
Example 1 (1.26 g) was dissolved in methylethylketone (30 ml) to give a 3.8% solution. The solution was spray dried using a Buchi B-191 with spray nozzle orifice diameter of 1.0 mm. The other spray drying parameters were as follows:
Temperature: 150° C., outlet temperature 106° C.
Solution flow rate: 15 ml/min
Atomisation Pressure: 2 Bar
Process gas flow rate 14 Cubic feet per minute (CFM)
A white powder was recovered from the cyclone and collection vessel, yield 37%. The spray drying process was successful at producing smooth, spherical particles of amorphous 6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester. The majority of the particles were between 0.5 and 4 μm.
Intermediate 5: 6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid Triethylamine Salt
A stirred suspension of Intermediate 3 (30 g) in ethylacetate (900 ml) is treated with triethylamine (1.05 molar equivalents, 8.6 ml) and the mixture is stirred at approximately 20° C. for 1.5 hours. The precipitate is filtered off, washed with ethylacetate (2×2 vol) and dried in vacuo at 45° C. for 18 hours to give title compound as a white solid (28.8 g, 80%). NMR (CDCl 3 ) δ: 7.59-7.47 (1H, m), 7.23-7.13 (1H, dd), 7.08-6.99 (1H, d), 6.54-6.42 (2H, m), 6.42-6.32 (1H, dd), 5.55-5.26 (1H, dddd 2 J H-F 50 Hz), 4.47-4.33(1H, bd), 3.88-3.70 (1H, bm), 3.31-3.09 (6H, q), 2.66-2.14 (5H, m), 1.93-1.69 (2H, m), 1.61-1.48 (3H, s), 1.43-1.33 (9H, t), 1.33-1.26 (1H, m), 1.26-1.15 (3H s), 1 11-0.97 (3H, d).
Pharmacological Activity
In Vitro Pharmacological Activity
Pharmacological activity was assessed in a functional in vitro assay of glucocorticoid agonist activity which is generally predictive of anti-inflammatory or anti-allergic activity in vivo.
For the experiments in this section, compound of formula (I) was used as unsolvated Form 1 (Intermediate 2)
The functional assay was based on that described by K. P. Ray et al., Biochem J. (1997), 328, 707-715. A549 cells stably transfected with a reporter gene containing the NF-κB responsive elements from the ELAM gene promoter coupled to sPAP (secreted alkaline phosphatase) were treated with test compounds at appropriate doses for 1 hour at 37° C. The cells were then stimulated with tumour necrosis factor (TNF, 10 ng/ml) for 16 hours, at which time the amount of alkaline phosphatase produced is measured by a standard colourimetric assay. Dose response curves were constructed from which EC 50 values were estimated.
In this test the compound of formula (1) showed an EC 50 value of <1 nM.
The glucocorticoid receptor (GR) can function in at least two distinct mechanisms, by upregulating gene expression through the direct binding of GR to specific sequences in gene promoters, and by downregulating gene expression that is being driven by other transcription factors (such as NFκB or AP-1) through their direct interaction with GR.
In a variant of the above method, to monitor these functions, two reporter plasmids have been generated and introduced separately into A549 human lung epithelial cells by transfection. The first cell line contains the firefly luciferase reporter gene under the control of a synthetic promoter that specifically responds to activation of the transcription factor NFκB when stimulated with TNFα. The second cell line contains the renilla luciferase reporter gene under the control of a synthetic promotor that comprises 3 copies of the consensus glucocorticoid response element, and which responds to direct stimulation by glucocorticoids. Simultaneous measurement of transactivation and transrepression was conducted by mixing the two cell lines in a 1:1 ratio in 96 well plate (40,000 cells per well) and growing overnight at 37° C. Test compounds were dissolved in DMSO, and added to the cells at a final DMSO concentration of 0.7%. After incubation for 1 h 0.5 ng/ml TNFα (R&D Systems) was added and after a further 15 hours at 37° C., the levels of firefly and renilla luciferase were measured using the Packard Firelite kit following the manufacturers' directions. Dose response curves were constructed from which EC 50 values were determined.
Transactivation (GR)
Transrepression (NFκB)
ED 50 (nM)
ED 50 (nM)
Compound of Formula
0.06
0.20
(I)
Metabolite (X)
>250
>1000
Fluticasone propionate
0.07
0.16
In vivo Pharmacological Activity
Pharmacological activity in vivo was assessed in an ovalbumin sensitised Brown Norway rat eosinophilia model. This model is designed to mimic allergen induced lung eosinophilia, a major component of lung inflammation in asthma.
For the experiments in this section, compound of formula (I) was used as unsolvated Form 1.
Compound of formula (I) produced dose dependant inhibition of lung eosinophilia in this model after dosing as an intra-tracheal (IT) suspension in saline 30 min prior to ovalbumin challenge. Significant inhibition is achieved after a single dose of 30 μg of compound of formula (I) and the response was significantly (p=0.016) greater than that seen with an equivalent dose of fluticasone propionate in the same study (69% inhibition with compound of formula (I) vs 41% inhibition with fluticasone propionate).
In a rat model of thymus involution 3 daily IT doses of 100 μg of compound (I) induced significantly smaller reductions in thymus weight (p=0.004) than an equivalent dose of fluticasone propionate in the same study (67% reduction of thymus weight with compound (I) vs 78% reduction with fluticasone propionate).
Taken together these results indicate a superior therapeutic index for compound (I) compared to fluticasone propionate.
In vitro Metabolism in Rat and Human Hepatocytes
Incubation of compound (I) with rat or human hepatocytes shows the compound to be metabolised in an identical manner to fluticasone propionate with the 17-β carboxylic acid (X) being the only significant metabolite produced. Investigation of the rate of appearance of this metabolite on incubation of compound (I) with human hepatocytes (37° C., 10 μM drug concentration, hepatocytes from 3 subjects, 0.2 and 0.7 million cells/mL) shows compound (I) to be metabolised ca. 5-fold more rapidly than fluticasone propionate:
17-β acid metabolite
Subject
Cell density
production (pmol/h)
number
(million cells/mL)
Compound (I)
Fluticasone propionate
1
0.2
48.9
18.8
1
0.7
73.3
35.4
2
0.2
118
9.7
2
0.7
903
23.7
3
0.2
102
6.6
3
0.7
580
23.9
Median metabolite production 102-118 pmol/h for compound (I) and 18.8-23.0 pmol/h for fluticasone propionate.
Pharmacokinetics After Intravenous (IV) and Oral Dosing in Rats
Compound (I) was dosed orally (0.1 mg/kg) and IV (0.1 mg/kg) to male Wistar Han rats and pharmacokinetic parameters determined. Compound (I) showed negligible oral bioavailability (0.9%) and plasma clearance of 47.3 mL/min/kg, approaching liver blood flow (plasma clearance of fluticasone propionate=45.2 mL/min/kg).
Pharmacokinetics After Intra-tracheal Dry Powder Dosing in the Pig.
Anaesthetised pigs (2) were dosed intra-tracheally with a homogenous mixture of compound (I) (1 mg) and fluticasone propionate (1 mg) as a dry powder blend in lactose (10% w/w). Serial blood samples were taken for up to 8 h following dosing.
DETAILED DESCRIPTION
Plasma levels of compound (I) and fluticasone propionate were determined following extraction and analysis using LC-MS/MS methodology, the lower limits of quantitation of the methods were 10 and 20 pg/mL for compound (I) and fluticasone propionate respectively. Using these methods compound (I) was quantifiable up to 2 hours after dosing and fluticasone propionate was quantifiable up to 8 hours after dosing. Maximum plasma concentrations were observed for both compounds within 15 min after dosing. Plasma half-life data obtained from IV dosing (0.1 mg/kg) was used to calculate AUC (0-inf) values for compound (I). This compensates for the plasma profile of Compound (I) only being defined up to 2 hours after an IT dose and removes any bias due to limited data between compound (I) and fluticasone propionate.
C max and AUC (0-inf) values show markedly reduced systemic exposure to compound (I) compared to fluticasone propionate:
AUC (0-inf)
Cmax (pg/mL)
(hr · pg/mL)
Pig 1
Pig 2
Pig 1
Pig 2
Compound of Formula (I)
117
81
254
221
Fluticasone propionate
277
218
455
495
The pharmacokinetic parameters for both compound (I) and fluticasone propionate were the same in the anaesthetised pig following intravenous administration of a mixture of the two compounds at 0.1 mg/kg. The clearance of these two glucocorticoids is similar is this experimental pig model.
EXAMPLES
Example 1
6α, 9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with Acetone
A solution of Intermediate 3 (530.1 g, 1 wt) in dimethylformamide (DMF) (8 vol) is treated with potassium hydrogen carbonate (0.202 wt, 1.02 eq) and the mixture cooled to −17±3° C. with stirring. Bromofluoromethane (BFM) (0.22 wt, 0.99 eq) is then added and the reaction stirred at −17±3° C. for at least 2 h. The reaction mixture is then added to water (17 vol) at 5±3° C. over ca 10 min followed by a water (1 vol) line wash. The suspension is stirred at 5-10° C. for at least 30 min and then filtered. The filter cake (the 6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester composition with DMF) is washed with water (4×4 vol) and the product is pulled dry on the filter. The damp cake is returned to the vessel, acetone (5.75 vol) added and heated at reflux for 2 h. The mixture is cooled to 52±3° C. and water (5.75 vol) added, keeping temperature at 52±3° C. The mixture is then cooled to 20+3° C., filtered and dried in vacuo at 60±5° C. overnight to give the title compound as a white solid (556.5 g, 89%). NMR δ (CDCl 3 ) includes the peaks described in Intermediate 2 for the unsolvated compound and the following additional solvent peaks: 2.17 (6H, s).
Example 1
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with Acetone (Alternative Method)
Intermediate 2 (1.0 g) was dissolved in approximately 60 volumes of acetone (60 mL) at reflux. The solvent level was reduced at reflux until the solution became cloudy before the flask was cooled to 21° C. over approximately 30 minutes. The flask was cooled in an ice bath for 30 minutes before the white precipitate was recovered by filtration and dried on the filter under vacuum for 30 minutes to afford the title compound (0.80 g) as a white solid.
Stoichiometry of compound of formula (I): guest=1:0.94 from 1 H nmr (CDCl 3 )
Example 1
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with Acetone (Second Alternative Method)
Intermediate 2 (75.0 g) was dissolved in approximately 34 volumes of acetone (2550 mL) and approximately 3.7 volumes of water by heating at reflux for 15 minutes. The solution was cooled to 50° C. over approximately 30 minutes and a mixture of acetone (2 volumes, 150 mL) and water (0.3 volumes, 22 mL) was added to simulate a line wash. The reaction mixture was cooled to approximately 40° C. over 30 minutes and seed crystals of Intermediate 2 (0.75 g, 0.01 weights) were added. The reaction mixture was further cooled to approximately 22° C. over 30 minutes and then stirred at approximately 22° C. for 15 minutes. Water (30 volumes, 2250 ml) was then added to the mixture over 30 minutes and the suspension stirred at approximately 22° C. for a further 30 minutes. The suspension was filtered and the bed washed with a mixture of acetone (2 vol, 150 mL) and water (1 volume, 75 mL). The product was dried at 60° C. for 18 hours to afford the title compound (80.7 g) as a white solid.
Example 2
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition wth Methylethylketone
A suspension of Intermediate 2 (400 mg) in methylethylketone (3.2 ml) is heated to reflux giving a clear solution. A portion of the solvent is distilled off at atmospheric pressure (approx 1 ml) and the mixture cooled to approximately 20° C. The crystallised product is filtered off, dried at approximately 20° C. under vacuum to leave the title compound as a white solid (310 mg, 68%). NMR δ((CDCl 3 ) includes the peaks described for Intermediate 2 and the following additional solvent peaks: 2.45 (2H, q), 2.14 (3H, s), 1.06 (3H, t).
Example 3
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with Propanol-2-ol
A solution of Intermediate 2 (150 mg) in propan-2-ol (15 ml) is left to slowly crystallise over a period of approximately 8 weeks. The resultant chunky crystals are isolated by filtration to leave the title compound as a white solid. NMR δ((CDCl 3 ) includes the peaks described for Intermediate 2 and the following additional solvent peaks: 4.03 (1H, m), 1.20 (6H, d).
Example 3
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with Propan-2-ol (Alternative Method)
A sample of Intermediate 2 (1.0 g) was dissolved in approximately 80 volumes of propan-2-ol (80 mL) at reflux. The solvent level was reduced at reflux until crystallisation began before the flask was cooled to 21° C. over approximately 30 minutes. The white precipitate was recovered by filtration and dried on the filter under vacuum for 30 minutes to afford the title compound as a white solid. Stoichiometry of compound of formula (I): guest=1:0.90 from 1 H nmr (CDCl 3 )
Example 3
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with Propan-2-ol (Second Alternative Method)
A sample of Intermediate 2 (82 g) was dissolved in a mixture of propan-2-ol (900 ml mL) and ethyl acetate (900 ml) at reflux. The solvent level was reduced by distillation at atmospheric distillation to approximately 12 volumes (985 ml) and the mixture seeded with authentic crystals of the desired product (ie composition with propan-2-ol, approximately 100 mg). The hot solution was cooled to 21° C. over approximately 3 hours during which time crystallisation occurred. The suspension was stirred at approximately 21° C. for 72 hours. The white precipitate was recovered by filtration and dried in vacuo to afford the title compound as a white solid (85.8 g).
Stoichiometry of compound of formula (I): guest=1:1 from 1 H nmr (CDCl 3 )
The propan-2-ol can be removed by the following process:
The product of Example 3 (second alternative method) (85.9 g) is heated under vacuum at 105 to 115° C. for at least 12 hours to give Intermediate 2 (77.2 g).
Example 4
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with Tetrahydrofuran
A suspension of Intermediate 2 (150 mg) in THF (20 vol) is warmed to give a clear solution. The solvent is allowed to slowly evaporate over a period of 6 days to leave title compound as a white solid. Alternatively, the THF solution is added dropwise to solution of potassium bicarbonate (2% w/w) in water (50 vol) and the precipitated product collected by filtration to furnish the title compound as a white solid. NMR δ (CDCl 3 ) includes the peaks described for Intermediate 2 and the following additional solvent peaks: 3.74 (4H, m), 1.85 (4H, m).
Example 4
6α,9α-Difluoro-17α-[(2-furanylcarbonyloxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with Tetrahydrofuran (First Alternative Method)
A mobile suspension of Intermediate 5 (1.2 g) in THF (10 ml) is treated with a phase transfer catalyst (tetrabutylammonium bromide, typically between 8 and 14 mol %), cooled to approximately 3° C. and treated with bromofluoromethane (0.98 equivalents). The suspension is stirred for between 2 and 5 hours, allowing to warm to 17° C. The reaction mixture is poured into water (30 vol), stirred at approximately 10° C. for 30 minutes and filtered off. The collected solid is washed with water (4×3 vol) and the product oven dried under vacuum at 60° C. overnight to give the title compound as a white solid (0.85 g, 87%).
Example 4
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with Tetrahydrofuran (Second Alternative Method)
Intermediate 2 (5.0 g) was dissolved in approximately 60 volumes of tetrahydrofuran (300 mL) at reflux. The solvent level was reduced at reflux until the solution became cloudy before the flask was cooled to 21° C. over approximately 30 minutes. The white precipitate was recovered by filtration and dried on the filter under vacuum for 60 minutes to afford the title compound (4.86 g) as a white solid. Stoichiometry of compound of formula (I): guest=1:0.95 from 1 H nmr (CDCl 3 )
Example 5
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with Dimethylformamide
A mixture of Intermediate 3 (4.5 g, 8.88 mmol) in dimethylformamide (DMF) (31 ml) is treated with potassium bicarbonate (0.89 g, 8.88 mmol) and the mixture is cooled to −20° C. A solution of bromofluoromethane (0.95 g, 8.50 mmol, 0.98 eqv.) in dimethylformamide (DMF) (4.8 ml) at 0° C. is added and the mixture is stirred at −20° C. for 4 hours. The mixture is then stirred at −20° C. for a further 30 minutes, added to 2M hydrochloric acid (100 ml) and stirred for a further 30 minutes at 0-5° C. The precipitate collected by vacuum filtration, washed with water and dried at 50° C. to give the title compound (4.47 g, 82%). NMR δ((CD 3 OD) includes the peaks described for Intermediate 2 and the following additional solvent peaks: 7.98 (1H, bs), 2.99 (3H, s), 2.86 (3H, s).
Example 6
6α,9α-Difluoro-17α[(2-furanylcarbonyl)oxy-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with Butan-1-ol
A mixture of Intermediate 4A (400 mg) and butan-1-ol (4 mL) was slurried at 21° C. for 61 hours. The solid was collected by filtration, dried on the filter for 2 hours and then dried under vacuum at 21° C. for 19 hours to afford the title compound as a white solid (401 mg).
Stoichiometry of compound of formula (I): guest=1:1.2 from 1 H nmr (CDCl 3 )
Example 7
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with Methyl Acetate
A sample of Intermediate 2 (100 mg) was dissolved in methyl acetate (6 mL) at reflux. The solvent level was reduced to approximately 1-2 mL and the flask was removed from the heat, cooled and sealed. After sifting for 72 hours crystals of the title compound were observed in the flask.
Stoichiometry of compound of formula (I): guest=1:0.9 from 1 H nmr (CDCl 3 )
Example 7
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with Methyl Acetate (Alternative Method)
Intermediate 4A (400 mg) was slurried in methyl acetate (2 mL) at 21° C. for 5 hours. The slurry was cooled in an ice/salt bath for 20 minutes before the white solid was recovered by filtration, dried on the filter for 30 minutes and then for 2 hours at 21° C. under vacuum. An nmr showed the solvent level was less than one equivalent. The sample was placed in a methyl acetate atmosphere for 48 hours to afford the title compound (350 mg).
Stoichiometry of compound of formula (I): guest=1:1.0 from 1 H nmr (CDCl 3 )
Example 8
6α,9α-Difluoro-17α[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with Acetic Acid
A mixture of acetic acid (2 mL) and Intermediate 4A (400 mg) was slurried at 21° C. for 16 hours. The solid was recovered by filtration, dried on the filter for 1 hour at 21° C. and then dried under vacuum for 16 hours at 40° C. and 16 hours at 60° C., to afford the title compound (420 mg).
Stoichiometry of compound of formula (I): guest=1:1.3 from 1 H nmr (CDCl 3 )
Example 9
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with Propan-1-ol
A mixture of Intermediate 4A (400 mg) and propan-1-ol (2 mL) was slurried at 21° C. for 61 hours. The solid was collected by filtration, dried on the filter for 30 minutes and then dried under vacuum at 21° C. for 19 hours to afford the title compound as a white solid (390 mg).
Stoichiometry of compound of formula (I): guest=1:1.1 from 1 H nmr (CDCl 3 )
Example 10
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16β-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with Ethanol
The product of Example 3 (500 mg) was slurried in ethanol (5 mL) under vacuum at 21° C. for a total of 16 hours, replacing the ethanol as necessary. The solid was collected by filtration and dried on the filter for 2 hours to give the title compound as a white solid (438 mg).
Stoichiometry of compound of formula (I): guest=1:1.0 from 1 H nmr (CDCl 3 )
Example 11
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with Ethyl Formate
Intermediate 4A (400 mg) was slurried in ethyl formate (2 mL) for 16 hours at 21° C. The solid was recovered by filtration and dried on the filter for 20 minutes to afford the title compound (396 mg).
Stoichiometry of compound of formula (I): guest=1:1.0 from 1 H nmr (CDCl 3 )
Example 12
6,9-Difluoro-17-[(2-furanylcarbonyl)oxy]-1-hydroxy-16-methyl-3-oxo-androsta-1,4-diene-17-carbothioic Acid S-fluoromethyl Ester
Composition with 1,4-dioxane
A mixture of 1,4-dioxane (2.7 mL) and Intermediate 4A (270 mg) was slurried at 21° C. for 2 hours. The solid was recovered by filtration, dried on the filter for 1.5 hour at 21° C. and then dried under vacuum for 18 hours at 21° C. and 24 hours at 40° C., to afford the title compound (240 mg).
Stoichiometry of compound of formula (I): guest=1:1.25 from 1 H nmr (CDCl 3 )
Example 12
6,9-Difluoro-17-[(2-furanylcarbonyl)oxy]-1-hydroxy-16-methyl-3-oxo-androsta-1,4-diene-17-carbothioic Acid S-fluoromethyl Ester
Composition with 1,4-dioxane (Alternative Method)
Intermediate 2 (1 g) was disolved in a mixture of 1,4-dioxane (40 mL) water (0.6 mL) at reflux and allowed to cool to approximately 27° C. The solution was added to stirred water (50 ml) over approximately 45 minutes. The suspension was stirred at approximately 20° C. for 1 hour. The solid was recovered by filtration and then dried under vacuum for 18 hours at 60° C. and 4 hours at 80° C., to afford the title compound (1.07 g).
Stoichiometry of compound of formula (I): guest=1:0.99 from 1 H nmr (CDCl 3 )
Example 13
6α,9α-Difluoro-17α-(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with Dimethylsulfoxide
A mixture of Intermediate 4A (400 mg) and dimethylsulfoxide (2 mL) was slurried at 21° C. for 30 minutes. The white solid was collected by filtration and dried in a dessicator over phosphorus pentoxide under high vacuum at 21° C. for 3 hours to afford the title compound.
Stoichiometry of compound of formula (I): guest=1:1.2 from 1 H nmr (CDCl 3 )
Example 14
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with N-methyl-2-pyrrolidinone
Intermediate 2 (100 mg) was disolved in N-methyl-2-pyrrolidinone (1 mL) at approximately 20° C. The solution was added to a solution of potassium hydrogen carbonate (100 mg) in water (5 ml) over approximately 10 seconds. The solid was recovered by filtration and then dried under vacuum at approximately 60° C. for 16 hours to afford the title compound.
Stoichiometry of compound of formula (I): guest=1:0.9 from 1 H nmr (CDCl 3 )
Example 15
6α,9α-Difluoro-17α-(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with Dimethylacetamide
Intermediate 2 (100 mg) was disolved in dimethylacetamide (0.5 mL) at approximately 20° C. and left to slowly crystalise over a period of 6 days. The solid was recovered by filtration and then dried under vacuum at approximately 60° C. for 16 hours to afford the title compound.
Stoichiometry of compound of formula (I): guest=1:1 from 1 H nmr (CDCl 3 )
Example 16
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with Water
Intermediate 4A (500 mg) was slurried in water (10 mL) for 16 hours. The solid was collected by filtration, dried for 16 hours under vacuum at 21° C., and then placed in a humid atmosphere for 48 hours to afford the title compound (444 mg) as a white solid.
Stoichiometry of compound of formula (I): guest=1:1 from water analysis.
Example 17
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester
Composition with ε-caprolactam
ε-Caprolactam (50 mg) (Aldrich) was heated in a glass vial to 80° C. where the solid had melted. Intermediate 4A (200 mg) was added and the mixture was agitated using a small magnetic stirrer bar. The mixture was stirred at 80° C. for 1 hour before the resulting mixture was allowed to cool to 21° C. and the solid was recovered to afford the title compound.
Further Characterising Data on Compositions of the Invention:
Detailed XRPD profile peak information for various compositions of the invention is provided in Tables 2 to 19.
Positions of bands in the Raman spectrum of various compositions of the invention are provided in Table 20.
The XRPD profiles of various compositions of the invention are provided in FIG. 4 and in detail in FIGS. 17-34.
The Raman spectra of various compositions of the invention are provided in FIGS. 9 to 16 .
We also claim compositions of the invention substantially by reference to their XRPD profiles and/or their Raman spectra as shown in the Figures and Tables.
Example A
Dry Powder Composition Containing 6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester Composition with Acetone
A dry powder formulation may be prepared as follows:
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester, composition with acetone prepared according to Example 1, MMD of 3 μm: 0.20 mg
milled lactose (wherein not greater than 85% of particles have a MMD of 60-90 μm, and not less than 15% of particles have a MMD of less than 15 μm): 12 mg
A peelable blister strip containing 60 blisters each filled with a formulation as just described may be prepared.
Example B
Dry Powder Composition Containing 6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester Composition with Acetone and a Long Acting β 2 -adrenoreceptor Agonist
A dry powder formulation may be prepared as follows:
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester composition with acetone prepared according to Example 1, MMD of 3 μm: 0.20 mg
Long-acting β 2 -adrenoreceptor agonist (micronised to a MMD of 3 μm): 0.02 mg
milled lactose (wherein not greater than 85% of particles have a MMD of 60-90 μm, and not less than 15% of particles have a MMD of less than 15 μm): 12 mg
A peelable blister strip containing 60 blisters each filled with a formulation as just described may be prepared.
Example C
Aerosol Formulation Containing 6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester Composition with Acetone
prepared according to Example 1, MMD of 3 μm:
An aluminium canister may be filled with a formulation as follows:
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester composition with acetone prepared according to Example 1, MMD of 3 μm: 250 μg
1,1,1,2-tetrafluoroethane: to 50 μl
(amounts per actuation)
in a total amount suitable for 120 actuations and the canister may be fitted with a metering valve adapted to dispense 50 μl per actuation.
Example D
Aerosol Formulation Containing 6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester Composition with Acetone and a Long Acting β 2 -adrenoreceptor Agonist
An aluminium canister may be filled with a formulation as follows:
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester composition with acetone prepared according to Example 1, MMD of 3 μm: 250 μg
Long-acting β 2 -adrenoreceptor agonist (micronised to a MMD of 3 μm): 25 μg
1,1,1,2-tetrafluoroethane: to 50 μl
(amounts per actuation)
in a total amount suitable for 120 actuations and the canister may be fitted with a metering valve adapted to dispense 50 μl per actuation.
Example E
Nasal Formulation Containing 6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic Acid S-fluoromethyl Ester Composition with Acetone
A formulation for intranasal delivery may be prepared as follows:
6α,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester composition with acetone prepared according to Example 1, MMD of 3 μm: 10 mg
Polysorbate 20 0.8 mg
Sorbitan monolaurate 0.09 mg
Sodium dihydrogen phosphate dihydrate 94 mg
Dibasic sodium phosphate anhydrous 17.5 mg
Sodium chloride 48 mg
Demineralised water to 10 ml
The formulation may be fitted into a spraypump capable of delivering a plurality of metered doses (Valois).
Throughout the specification and the claims which follow, unless the context requires otherwise, the word ‘comprise’, and variations such as ‘comprises’ and ‘comprising’, will be understood to imply the inclusion of a stated integer or step or group of integers but not to the exclusion of any other integer or step or group of integers or steps.
The patents and patent applications described in this application are herein incorporated by reference.
TABLE 2
XRPD characteristic angles and relative
intensities for 6α, 9α-Difluoro-17α-
[(2-furanylcarbonyl)oxy]-11β-hydroxy-
16α-methyl-3-oxo-androsta-1,
4-diene-17β-
carbothioic acid S-fluoromethyl ester, composition with acetone.
Relative
Angle
Intensity
°2Theta
%
9.5
5.4
10.9
38.1
12.4
16.5
13.1
28.3
14.1
24.1
14.5
23.3
15.1
19.5
15.7
100.0
16.8
70.5
17.4
32.0
17.9
43.8
18.3
4.7
18.9
23.6
19.3
28.9
19.8
42.7
20.3
14.0
21.6
30.3
22.0
44.4
22.4
22.1
22.7
9.5
23.3
10.8
23.6
9.5
24.0
4.7
24.7
14.8
25.1
40.4
25.4
44.4
25.8
24.4
26.4
8.4
27.1
10.3
27.5
23.9
28.0
9.0
28.6
15.2
29.1
10.4
30.1
14.8
30.5
10.4
31.2
12.9
31.7
5.5
32.5
6.2
32.9
8.8
33.6
7.4
33.9
7.4
34.3
6.7
34.8
6.3
35.3
9.9
35.7
6.7
36.1
18.2
37.0
6.7
37.6
17.3
38.7
8.5
39.0
6.3
39.6
8.1
40.0
9.1
40.8
4.5
41.2
6.2
41.5
5.3
42.0
4.8
42.8
5.1
43.6
3.5
44.0
5.8
44.7
4.8
TABLE 3
XRPD characteristic angles and relative intensities
for 6α, 9α-Difluoro-17α-
[(2-furanylcarbonyl)oxy]-11β-hydroxy-
16α-methyl-3-oxo-androsta-1,4-diene-17β-
carbothioic acid S-fluoromethyl ester,
composition with methylethylketone.
Relative
Angle
Intensity
°2Theta
%
7.3
8.7
8.0
38.0
8.5
10.4
9.3
27.7
9.8
22.0
10.8
100.0
11.2
11.2
11.8
15.3
12.4
50.1
13.1
62.0
13.5
8.8
13.9
43.3
14.4
38.3
15.0
36.7
15.5
98.3
16.1
16.1
16.6
62.0
17.3
49.3
17.8
60.0
18.6
16.3
18.8
26.7
19.1
24.9
19.6
37.1
20.0
13.9
20.3
5.1
20.8
5.0
21.5
32.4
21.7
43.0
22.2
16.9
22.5
15.5
23.1
13.6
23.3
9.8
23.7
9.6
24.5
16.8
25.0
31.8
25.2
32.6
25.5
26.2
25.9
7.1
26.2
9.0
26.9
14.1
27.2
16.2
27.9
15.5
28.4
12.3
28.9
15.2
29.8
12.8
30.1
9.8
30.4
10.4
31.0
15.7
31.6
6.1
32.2
8.6
32.5
8.9
33.3
9.5
33.6
10.7
33.9
6.6
34.2
6.5
34.5
6.2
34.9
8.3
35.2
8.3
35.7
16.6
36.6
7.3
37.3
20.2
38.3
8.5
39.0
6.2
39.5
8.6
39.8
10.0
40.4
5.6
41.0
6.2
41.7
5.9
42.3
6.6
42.7
4.7
43.0
4.1
43.6
7.1
44.2
4.8
TABLE 4
XRPD characteristic angles and relative intensities
for 6α, 9α-Difluoro-17α-
[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-
methyl-3-oxo-androsta-1,4-diene-17β-
carbothioic acid S-fluoromethyl ester,
composition with propan-2-ol.
Relative
Angle
Intensity
°2Theta
%
8.1
9.1
9.2
100
10.8
16.5
11.2
.5
12.7
3.7
13.0
5.2
13.3
4.1
13.7
6.2
14.5
5.2
14.8
4.7
15.3
12.6
16.4
10.6
17.9
2.9
18.3
5.5
18.5
9.8
19.0
3.6
19.3
7.6
19.8
3.7
21.6
4.2
22.1
6.2
22.7
6.7
22.9
0.6
23.5
0.5
24.2
1.8
24.5
1.1
24.9
3.2
25.1
4.3
25.5
1.6
26.4
0.5
26.9
1.7
27.3
1.5
27.8
2.5
28.4
1.5
28.8
0.8
29.2
1.6
29.8
3.7
31.0
0.6
31.5
0.8
31.8
0.7
32.5
1.5
32.8
0.9
33.4
1.8
34.0
0.9
34.3
1.4
34.9
1.4
35.4
0.4
35.9
0.9
36.3
0.7
37.2
0.7
37.8
1.6
38.4
0.9
38.9
0.5
39.5
0.8
40.2
0.7
40.6
0.6
41.5
1.1
42.2
0.8
42.4
0.9
43.1
0.8
43.4
1.0
44.0
0.5
44.6
0.5
TABLE 5
XRPD characteristic angles and relative intensities
for 6α, 9α-Difluoro-17α-
[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-
methyl-3-oxo-androsta-1,4-diene-17β-
carbothioic acid S-fluoromethyl ester,
composition with tetrahydrofuran.
Relative
Angle
Intensity
°2Theta
%
2.1
74.7
8.1
25.9
9.5
41.6
9.7
33.5
10.9
100.0
11.6
10.7
12.4
44.0
13.2
37.9
13.7
17.2
14.1
21.0
14.3
31.2
15.1
44.0
15.5
90.0
16.7
74.4
17.3
55.9
17.8
54.0
18.8
54.3
19.1
32.6
19.7
40.8
20.2
14.9
21.5
38.2
21.8
42.1
22.4
18.1
23.3
22.1
23.7
7.8
24.0
10.3
24.4
13.5
25.0
33.1
25.5
14.0
25.9
16.9
26.2
13.2
26.6
5.7
26.9
12.9
27.3
15.5
27.9
10.7
28.5
12.5
28.9
10.0
29.3
5.9
29.8
9.0
30.4
14.7
30.9
9.7
31.5
6.5
32.2
6.7
32.8
9.0
33.6
9.0
34.3
8.1
34.6
6.7
35.1
5.9
36.0
11.3
36.8
5.9
37.4
9.9
38.1
5.3
38.4
6.7
39.2
5.7
39.7
9.0
40.5
6.5
41.3
5.7
41.9
4.3
42.3
4.5
43.1
4.2
43.5
3.6
43.9
4.0
44.5
5.9
TABLE 6
XRPD characteristic angles and relative intensities
for 6α, 9α-Difluoro-17α-
[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-
methyl-3-oxo-androsta-1,4-diene-17β-
carbothioic acid S-fluoromethyl ester,
composition with dimethylformamide.
Relative
Angle
Intensity
°2Theta
%
7.9
3.4
9.1
2.4
10.8
12.6
12.4
14.6
13.1
21.7
14.0
20.3
14.4
29.0
15.5
100.0
16.6
57.7
17.4
66.1
17.9
75.1
18.8
36.4
19.1
50.4
19.6
45.6
20.1
17.0
21.5
62.4
21.8
71.2
22.3
34.1
22.6
11.3
23.1
24.6
23.8
10.8
24.4
30.6
25.0
94.7
25.6
35.5
26.0
15.2
26.3
21.7
27.0
32.3
27.2
31.9
28.0
30.6
28.4
25.0
29.0
22.8
29.7
26.9
30.2
17.6
31.1
29.0
31.6
14.6
32.1
17.6
32.7
15.8
33.4
27.7
33.7
17.6
34.5
12.9
34.9
17.0
35.3
18.6
35.8
40.6
36.7
22.0
37.4
36.8
38.2
16.4
38.4
17.6
39.1
15.8
39.6
17.6
39.9
19.6
40.4
10.5
41.1
21.7
41.8
14.0
42.3
15.2
42.7
10.3
43.6
13.4
44.4
13.7
TABLE 7
XRPD characteristic angles and relative intensities
for 6α, 9α-Difluoro-17α-
[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-
methyl-3-oxo-androsta-1,4-diene-17β-
carbothioic acid S-fluoromethyl ester,
composition with butan-1-ol.
Relative
Angle
Intensity
°2Theta
%
8.0
40.1
9.0
77.9
9.6
1.6
10.6
64.6
11.4
2.2
12.7
26.4
13.2
17.9
13.4
30.5
14.0
20.0
14.4
36.9
15.1
100.0
16.1
49.6
17.5
9.5
17.8
9.3
18.1
31.7
18.6
36.1
18.8
61.7
19.0
41.4
19.4
9.7
21.3
18.2
21.6
30.8
21.9
19.3
22.6
6.7
22.9
6.2
23.3
5.8
24.0
17.9
24.6
25.0
25.0
10.5
25.2
9.1
25.7
4.8
26.6
9.0
27.0
6.3
27.6
11.7
28.0
11.0
28.7
8.7
29.1
8.5
29.4
8.1
30.4
4.7
30.9
5.6
31.3
4.3
31.9
6.7
32.2
8.5
33.2
5.7
33.5
7.6
33.8
7.5
34.1
4.7
35.0
3.9
35.5
5.8
36.3
4.3
37.1
3.2
37.7
7.2
38.5
3.8
39.0
5.6
39.6
5.0
40.3
3.0
41.1
3.1
41.6
2.8
42.1
3.9
43.0
3.8
43.4
3.1
44.1
3.3
TABLE 8
XRPD characteristic angles and relative intensities
for 6α, 9α-Difluoro-17α-
[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-
methyl-3-oxo-androsta-1,4-diene-17β-
carbothioic acid S-fluoromethyl ester,
composition with methyl acetate.
Relative
Angle
Intensity
°2Theta
%
5.4
0.9
8.1
18.9
9.4
28.3
9.7
28.3
10.8
99.5
11.6
7.8
12.3
48.6
12.9
27.8
13.2
34.9
13.7
15.2
14.0
38.4
14.7
12.2
15.1
39.5
15.5
100.0
15.7
19.5
16.6
91.2
17.2
40.1
17.7
50.3
18.7
38.7
18.9
42.9
19.6
37.2
20.2
15.0
21.4
42.3
21.8
50.6
22.3
18.5
23.3
21.3
23.9
10.5
24.3
12.6
24.9
37.2
25.4
16.0
25.9
16.9
26.0
13.1
26.8
11.1
27.2
23.5
27.7
13.1
28.4
12.2
28.7
11.3
29.2
9.0
29.7
9.6
30.3
19.1
30.8
15.4
31.4
5.6
31.9
4.9
32.1
6.6
32.7
14.3
33.2
8.0
33.5
9.2
34.3
7.9
34.6
8.3
35.0
7.8
35.9
16.2
37.3
17.3
38.3
9.6
39.1
8.2
39.5
10.0
40.3
7.5
41.2
7.0
41.8
6.3
42.3
5.9
43.0
5.3
43.4
5.7
44.4
6.8
TABLE 9
XRPD characteristic angles and relative intensities
for 6α, 9α-Difluoro-17α-
[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-
methyl-3-oxo-androsta-1,4-diene-17β-
carbothioic acid S-fluoromethyl ester,
composition with acetic acid.
Relative
Angle
Intensity
°2Theta
%
8.2
18.7
9.5
17.7
11.0
100.0
12.5
37.9
13.2
17.2
14.2
22.8
14.5
16.6
15.2
16.8
15.7
87.2
16.8
46.3
17.5
32.8
18.0
35.6
18.3
4.4
19.1
18.4
19.3
22.8
19.9
25.5
20.5
9.2
21.7
24.9
22.1
30.0
22.6
12.3
23.6
8.2
24.7
14.9
25.3
33.3
25.5
24.7
25.8
10.7
26.2
12.2
26.5
9.4
27.2
9.2
27.6
12.9
28.2
6.4
28.8
7.3
29.1
8.3
29.6
5.4
30.2
8.8
30.7
6.3
31.3
8.7
31.9
4.1
32.6
4.1
33.2
6.2
34.0
7.6
34.6
4.4
35.0
3.8
35.4
6.3
35.9
4.7
36.3
12.7
37.2
5.3
37.8
11.1
38.2
6.3
38.8
4.3
39.4
4.9
40.1
6.5
40.7
4.4
41.0
4.2
41.7
5.7
42.3
3.5
42.8
4.2
43.5
3.4
44.1
4.1
TABLE 10
XRPD characteristic angles and relative intensities
for 6α, 9α-Difluoro-
17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-
methyl-3-oxo-androsta-1,4-diene-17β-
carbothioic acid S-fluoromethyl ester,
composition with propan-1-ol.
Relative
Angle
Intensity
°2Theta
%
3.7
0.3
8.1
49.7
9.1
71.9
9.7
8.1
10.8
88.6
11.4
2.0
12.7
32.1
13.4
41.2
13.8
4.5
14.2
8.2
14.6
60.0
15.3
100.0
16.3
54.4
17.0
2.0
17.7
8.2
18.0
26.9
18.5
38.2
19.1
62.3
19.6
11.6
20.2
2.7
21.6
22.8
21.9
37.2
22.4
23.6
22.8
5.2
23.0
5.4
23.8
6.0
24.2
16.5
24.9
43.8
25.4
10.3
26.9
8.8
27.2
5.7
27.6
12.7
28.0
7.4
28.3
8.4
29.1
11.7
29.6
10.9
29.9
7.0
30.4
4.4
30.8
4.0
31.4
9.6
32.1
6.3
32.3
6.3
32.6
7.8
32.9
6.7
33.5
6.6
34.1
8.2
34.4
11.3
35.4
4.6
35.8
8.1
36.2
5.3
36.8
9.0
37.3
3.9
37.8
10.7
38.2
7.4
38.7
4.2
39.3
4.8
39.6
7.0
39.9
4.8
40.9
4.6
41.1
5.6
41.7
5.8
42.8
4.7
43.3
5.2
43.9
4.1
44.6
4.4
TABLE 11
XRPD characteristic angles and relative intensities
for 6α, 9α-Difluoro-
17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-
methyl-3-oxo-androsta-1,4-diene-17β-
carbothioic acid S-fluoromethyl ester,
composition with ethanol.
Relative
Angle
Intensity
°2Theta
%
2.8
0.6
8.2
34.2
9.3
37.3
10.9
100.0
11.3
6.1
12.8
25.6
13.0
12.9
13.4
40.3
13.7
11.3
14.6
38.6
14.9
24.0
15.4
59.3
16.3
12.4
16.5
42.1
18.0
26.0
18.4
48.4
19.2
23.4
19.4
27.5
19.8
10.1
21.8
30.1
22.2
20.4
22.8
9.3
23.5
2.2
24.4
9.6
25.1
30.3
25.6
12.2
26.6
3.8
27.2
8.3
27.6
11.7
28.2
6.9
28.5
9.0
29.2
6.8
29.5
9.5
30.0
9.3
31.5
5.6
32.0
4.9
32.6
7.3
32.9
6.6
33.7
6.9
34.1
3.7
34.5
6.8
35.0
6.2
36.0
8.1
36.7
3.9
37.3
3.4
37.9
9.4
38.7
4.8
39.7
4.8
40.0
3.7
40.3
3.7
40.8
4.2
41.5
4.5
42.1
3.7
42.7
3.2
43.6
5.3
44.3
3.2
TABLE 12
XRPD characteristic angles and relative intensities
for 6α, 9α-Difluoro-
17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-
methyl-3-oxo-androsta-1,4-diene-17β-
carbothioic acid S-fluoromethyl ester,
composition with ethyl formate.
Relative
Angle
Intensity
°2Theta
%
3.5
0.2
5.0
0.3
8.0
23.0
9.4
33.2
10.9
93.7
11.9
3.2
12.4
44.3
13.1
39.4
13.9
39.9
14.4
21.2
14.9
24.9
15.6
100.0
16.7
51.2
17.4
54.6
17.9
70.5
18.2
7.4
18.8
20.0
19.2
36.7
19.6
27.3
20.0
9.6
21.5
30.3
21.8
49.6
22.1
13.1
22.6
6.0
23.1
8.1
23.4
8.5
23.8
8.5
24.5
23.2
25.0
26.6
25.2
25.1
25.6
23.4
26.0
5.3
26.3
14.0
27.0
12.2
27.3
6.8
28.0
12.8
28.3
11.7
28.9
11.4
29.9
10.9
30.1
6.6
30.4
6.9
30.8
8.6
31.1
12.2
31.6
4.9
32.6
9.5
33.3
7.7
33.6
7.4
34.3
5.2
34.9
7.9
35.7
14.0
36.6
4.8
37.3
14.9
37.7
4.9
38.4
7.2
39.0
5.8
39.5
7.4
39.9
5.2
40.6
4.2
40.9
5.8
41.7
4.3
42.4
5.6
42.9
3.4
43.7
5.2
44.3
3.8
TABLE 13
XRPD characteristic angles and relative intensities for 6α,
9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-
16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid
S-fluoromethyl ester, composition with 1,4-dioxane.
Relative
Angle
Intensity
°2Theta
%
8.7
39.8
10.5
7.4
12.9
38.6
13.2
57.9
14.4
100.0
15.7
33.1
17.6
29.9
18.4
79.9
18.6
69.0
19.5
8.9
20.5
10.1
21.0
16.3
21.3
12.6
21.8
57.4
22.8
5.5
23.3
9.5
23.6
13.9
23.9
14.0
24.7
5.5
25.0
5.8
25.5
5.0
26.1
5.6
26.8
10.1
27.0
11.6
27.3
9.7
27.9
5.1
28.3
4.3
28.8
7.5
29.5
12.7
29.9
7.1
30.4
6.5
31.1
7.3
31.4
7.6
31.9
6.2
32.6
11.0
33.2
4.1
33.8
7.6
34.0
8.3
34.2
7.5
TABLE 14
XRPD characteristic angles and relative intensities for 6α,
9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-
16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid
S-fluoromethyl ester, composition with dimethylsulfoxide.
Relative
Angle
Intensity
°2Theta
%
8.1
19.9
9.4
11.5
10.8
73.1
12.4
44.0
13.0
31.0
14.0
21.5
14.4
45.0
15.0
28.5
15.4
100.0
15.6
27.7
16.5
66.2
17.4
65.3
17.8
70.5
19.0
47.1
19.6
68.3
20.3
17.4
21.5
64.5
21.8
49.3
22.3
34.9
23.1
15.9
23.6
6.4
24.2
25.8
25.0
88.0
25.5
24.2
25.9
16.1
26.8
34.9
27.1
16.3
27.8
17.6
28.5
23.7
28.8
26.8
29.5
13.0
30.3
12.2
30.9
18.3
32.8
12.4
33.7
8.9
TABLE 15
XRPD characteristic angles and relative intensities for 6α,
9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-
16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid
S-fluoromethyl ester, composition with N-methyl-2-pyrrolidinone.
Relative
Angle
Intensity
°2Theta
%
7.9
27.4
9.4
25.0
10.8
55.4
12.1
78.5
12.8
35.3
13.0
42.3
14.1
53.3
14.6
6.9
14.9
18.7
15.5
100.0
15.8
16.4
16.6
91.0
17.3
62.5
18.4
20.4
18.6
11.4
18.9
30.6
19.6
42.1
20.0
8.4
21.1
33.7
21.6
50.3
22.0
13.7
22.6
5.6
23.1
12.5
23.4
18.0
23.7
7.5
24.6
42.1
25.0
24.1
25.6
21.5
26.4
9.8
27.2
25.2
28.0
12.8
28.4
15.3
28.9
5.5
29.9
14.9
30.6
9.4
31.4
5.4
31.8
5.5
32.3
11.1
32.8
10.9
33.5
8.7
33.9
5.3
34.8
6.7
35.3
17.3
35.7
9.0
36.6
16.8
37.3
8.8
38.2
6.7
38.4
6.6
38.9
8.1
39.6
7.3
40.5
7.2
41.0
5.5
41.5
3.4
42.3
5.5
43.0
4.4
43.3
5.1
44.0
7.1
TABLE 16
XRPD characteristic angles and relative intensities
for 6α, 9α-Difluoro-
17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-
methyl-3-oxo-androsta-1,4-diene-17β-
carbothioic acid S-fluoromethyl ester,
composition with dimethyl acetamide.
Relative
Angle
Intensity
°2Theta
%
5.2
0.2
8.0
42.6
9.4
28.8
10.8
75.2
12.1
100.0
12.8
33.0
13.0
37.2
13.9
36.0
14.1
52.0
14.9
20.6
15.4
87.2
15.6
11.4
16.5
76.9
17.0
81.1
17.4
66.3
18.4
18.9
18.7
16.6
18.9
26.2
19.5
33.2
20.0
8.3
21.2
42.4
21.6
33.4
22.0
14.0
22.3
5.4
23.0
10.8
23.1
10.9
23.7
5.7
24.2
10.5
24.6
40.5
24.9
22.7
25.4
11.7
25.7
14.3
26.4
9.4
27.0
24.0
27.2
14.3
27.6
3.7
28.1
8.4
28.8
6.3
29.2
2.9
29.5
8.0
30.0
9.8
30.5
7.7
31.0
3.2
31.9
5.5
32.3
9.0
33.0
8.5
33.3
4.6
33.8
3.7
34.2
3.3
34.8
4.5
35.1
5.6
35.4
23.2
36.3
3.5
36.8
9.9
37.3
3.9
37.6
4.5
38.0
4.2
38.5
4.1
38.9
9.3
39.4
3.9
39.7
4.5
40.2
3.5
40.5
4.2
41.2
2.6
41.9
3.8
42.4
3.5
43.1
4.0
43.9
3.9
44.2
2.8
44.3
2.4
TABLE 17
XRPD characteristic angles and relative intensities for 6α,
9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-
16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid
S-fluoromethyl ester, composition with water.
Relative
Angle
Intensity
°2Theta
%
6.4
11.4
6.9
16.0
8.8
55.2
9.6
34.7
11.0
6.9
11.4
11.4
12.2
100.0
12.6
61.2
13.3
82.4
13.8
26.1
14.2
27.6
14.8
25.8
15.3
51.1
15.5
64.7
16.0
40.6
17.2
28.5
17.7
11.2
18.1
51.1
18.4
76.9
19.2
34.7
19.5
54.8
20.2
37.4
20.5
42.4
21.3
46.5
21.8
22.5
22.2
12.4
22.9
15.5
23.8
26.1
24.7
13.6
25.3
23.4
26.2
20.5
27.7
12.8
28.6
14.4
29.9
10.1
30.4
18.3
32.1
21.2
32.6
21.0
33.6
13.6
34.5
17.3
TABLE 18
XRPD characteristic angles and relative intensities
for 6α, 9α-Difluoro-
17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-
methyl-3-oxo-androsta-1,4-diene-17β-
carbothioic acid S-fluoromethyl ester,
composition with cyclopentanone.
Relative
Angle
Intensity
°2Theta
%
2.3
0.4
3.3
0.4
6.3
0.2
8.1
22.0
9.4
24.1
10.9
50.8
12.4
47.7
13.1
33.5
14.0
22.6
14.3
29.7
15.0
20.3
15.5
100.0
16.6
46.8
17.4
59.5
17.8
47.1
18.8
26.6
19.1
29.7
19.6
37.2
20.1
7.0
21.5
27.5
21.7
33.2
22.3
12.7
23.1
13.2
23.7
5.6
24.3
16.7
24.9
45.2
25.4
19.3
26.2
9.7
26.9
17.8
27.2
14.7
27.9
14.9
28.3
11.6
28.8
10.7
29.6
11.5
30.2
6.8
30.9
12.6
31.5
8.0
32.0
8.2
32.6
6.2
33.4
10.0
33.6
7.5
34.0
5.8
34.4
4.7
34.8
6.3
35.1
6.6
35.7
17.2
36.6
7.9
37.3
13.7
38.0
6.6
38.3
6.2
39.0
6.3
39.6
9.6
40.3
4.4
41.0
6.4
41.7
5.9
42.1
5.3
42.7
3.9
43.3
4.7
43.7
3.9
44.2
5.8
44.7
4.3
TABLE 19
XRPD characteristic angles and relative intensities for 6α,
9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-
16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid
S-fluoromethyl ester, composition with ε-caprolactam.
Relative
Angle
Intensity
°2Theta
%
7.8
64.0
9.0
32.0
10.5
53.9
12.0
90.0
12.6
44.3
13.3
9.7
13.9
51.8
14.4
35.0
15.1
100.0
16.1
44.7
16.9
86.2
17.4
72.0
18.3
42.8
18.6
71.5
18.9
65.4
21.1
34.6
21.4
29.2
21.9
14.2
22.3
19.6
22.7
15.8
23.8
25.6
24.2
37.7
24.5
43.6
25.5
10.6
26.3
21.2
27.3
21.7
28.1
18.9
29.0
23.9
29.5
12.6
30.0
13.8
30.8
15.3
32.3
16.7
33.9
16.9
34.7
20.6
TABLE 20
Raman band positions for various compositons with 6α,
9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-
16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid
S-fluoromethyl ester
Guest molecule
Band positions (cm −1 )
Butan-1-ol
3114, 3056, 2937, 2881, 1727, 1661, 1606, 1470,
1394, 1341, 1312, 1235, 1198, 1151, 1128, 1076,
997, 930, 883, 850, 817, 733, 702, 623, 597, 568,
548, 527, 414, 391, 373, 290, 245, 197, 176, 97
Methyl acetate
3146, 3047, 2967, 2942, 2882, 1730, 1669, 1636,
1611, 1569, 1471, 1393, 1340, 1309, 1235, 1200,
1151, 1112, 1075, 998, 934, 882, 858, 733, 700,
648, 596, 569, 547, 528, 413, 393, 375, 286, 237,
196, 175, 92
Acetic acid
3148, 3043, 2977, 2933, 2880, 1731, 1662, 1616,
1600, 1471, 1393, 1343, 1313, 1247, 1199, 1154,
1124, 1076, 998, 974, 931, 881, 734, 701, 598, 570,
554, 529, 415, 374, 286, 240, 184, 87
Propan-1-ol
3057, 2937, 2881, 1726, 1662, 1608, 1470, 1394,
1341, 1311, 1235, 1199, 1151, 1127, 1076, 997,
930, 883, 851, 733, 702, 622, 597, 567, 547, 528,
461, 414, 392, 374, 290, 244, 196, 176, 94
Ethanol
3058, 2944, 2881, 1726, 1662, 1620, 1608, 1470,
1393, 1341, 1310, 1235, 1199, 1151, 1125, 1076,
997, 930, 883, 732, 701, 597, 167, 547, 528, 415,
393, 375, 289, 245, 196, 176, 89
Ethyl formate
3113, 3046, 2975, 2946, 2881, 1729, 1696, 1667,
1394, 1342, 1311, 1236, 1199, 1153, 1124, 1075,
998, 937, 883, 730, 701, 597, 569, 550, 527, 413,
391, 287, 243, 195, 176, 88
1,4-dioxane
3149, 3046, 2974, 2936, 2883, 1726, 1669, 1635,
1611, 1568, 1471, 1392, 1342, 1308, 1236, 1200,
1152, 1127, 1075, 1015, 998, 932, 883, 835, 732,
700, 597, 568, 548, 528, 414, 392, 375, 286, 239,
195, 184, 172, 86
Dimethylsulphoxide
3146, 3045, 2983, 2943, 2916, 2878, 1723, 1666,
1633, 1608, 1569, 1470, 1416, 1394, 1342, 1310,
1236, 1199, 1152, 1125, 1075, 1040, 998, 972, 931,
882, 731, 701, 673, 597, 567, 549, 527, 414, 305,
286, 243, 196, 183, 87 | There is provided a crystalline chemical composition comprising a compound of formula (I)
in which the crystal lattice is stabilized by the presence of a guest molecule, characterized in the crystalline composition is of space group P2 1 2 1 2 1 having unit cell dimensions of about 12.1±0.6 Å, 14.9±0.7 Å, and 16.2±0.8 Å when determined at either 120K or 150K. | 2 |
BACKGROUND OF THE INVENTION
This invention relates to a retractable folding top for a convertible.
In the case of known folding tops for convertibles, the folding top, which is provided with a tightening clamp for the material of the top in the rear region, is locked in the closed position in its resting position on the cover for the storage well of the top, in each case a locking pin interacting with a forked torsion latch of a torsion latch lock and the cover for the storage well of the top being pivotable by means of a hydraulic driving mechanism into the opening and closing positions. The hydraulic driving cylinders, provided for this purpose as driving elements, are accommodated in the body region below the fender or the rear flap, so that the construction costs, as well as the space required, are disadvantageously increased and solutions of this type are not very suitable, especially for 4-seater convertibles.
SUMMARY OF THE INVENTION
It is an object of the invention to provide a retractable folding top for a convertible, the driving elements of which, disposed movably and in a space-saving manner with little technical effort, enable the folding top to be fixed carefully and reliably tight on the cover for the storage well of the top.
With the inventive construction of the retractable folding top with the actuating apparatus that can be used for jointly moving the tightening clamp for the material of the top and the cover for the storage well of the top, an effective connection of these components is possible with little constructive effort in such a way, that a simplification of the locking means, as well as, with little effort, an automatic control of the locking and unlocking of the tightening clamp for the material of the top and of the cover for the storage well of the top can be achieved.
With the actuating equipment, a pivoting/pushing motion can be imparted during the closing process to the cover of the storage well for the top. With this motion and the simultaneous connecting engagement of closing part and locking equipment, a material-safeguarding, uniform tension can be imparted to the material of the folding top, so that, in the closed state, the folding top offers a fold-free, smooth roofing contour, which makes a decrease in driving noise possible.
The actuating equipment, which can be driven with little effort, can be provided with a driving unit of small construction, so that such a folding top can be used advantageously for 4-seater convertibles with confined space relationships in the rear region of the vehicle.
Further details and advantages of the invention arise out of the following description and the drawing, which illustrates an embodiment of an inventive, retractable folding top diagrammatically.
In the Drawings
FIG. 1 shows a partially opened up rear view of a convertible with a folding top in the closed position,
FIG. 2 shows a side view of the rear region along a line II--II of FIG. 1,
FIG. 3 shows a rear view, similar to that of FIG. 1, with a cover for a storage
well of a top in the open position,
FIG. 4 shows a perspective view similar to that of FIG. 3, with a cover for storage well of a top and a folding top interacting in a closing phase,
FIG. 5 shows a sectional side view of the rear region along a line V--V of FIG. 4,
FIG. 6 shows a perspective detailed representation of a reversing lever, which is provided at the cover for the storage well of a top,
FIG. 7 shows a perspective view of the reversing lever,
FIG. 8 shows a perspective detailed representation of a parallelogram hinge, which is provided between the cover for a storage well of the top and the vehicle body,
FIG. 9 shows a perspective detailed representation of locking equipment with a closing pans, and
FIG. 10 shows a side view of a catch hook engaging an anchoring bracket.
DESCRIPTION OF THE PREFERRED EMBODIMENT
In FIG. 1, a rear region of a convertible is illustrated, which is labeled 1 as a whole, and the closed folding top 2 which has a rear window 4 integrated in the roofing 3, below which rear window 4 the folding top 2 is put down in a storage well having a cover 6, which is in one plane with the trunk lid 5.
The sectional side vide of FIG. 2, when viewed in conjunction with FIG. 1, illustrates that the folding top 2 is provided with a frame 7, the rear termination of which is formed by a U-shaped tightening clamp 8 for the top and which is pivotably supported on the vehicle at 7a. Below a supporting plane formed by the cover 6 there is provided trough 9 which forms, a storage well 10 for the top into which the folded top 2 can be swiveled when the convertible is driven with the top down (not shown). For this purpose, the cover 6 for the storage well of the top in the closed position (FIG. 1), after the folding top 2 is lifted up, is swiveled into an open position (FIG. 3), the folded top 2 is placed in the storage well 10 and then covered by means of the storage well cover 6 for the storage well of the top.
If subsequently the convertible is used in the closed position (with the top up), the reverse of the sequence described above for the folding process is followed and the cover 6 for the storage well of the top is opened, the folded top 2 is swiveled out by means of the frame 7, brought into the closed position (FIG. 1) adjoining, on one side, the windshield frame (not shown) and, in this closed position, the folding top 2 is fixed over at least one closing part 13 at the tightening clamp 8 of the top and engaging the respective locking device 12 in the resting position on the cover 6 for the storage well of the top (FIG. 2). The closing part 13 and the locking equipment 12 together are sometimes hereinafter referred to as engageable means.
Partially broken away, sectional representation of FIG. 1 illustrates that the cover 6 for the storage well of the top is provided for these automatic motions in an advantageous development with actuating equipment, which is labeled 15 as a whole and which is described in greater detail hereinafter. During the closing process. The actuating equipment 15 brings about in the region of the respective pivoting mountings 16 hereinafter further described, a horizontal control motion at least in phases in such a manner, that the closing part 13 is taken hold of at the tightening clamp 8 for the material of the top by the locking equipment 12 (FIG. 5) and the folding top 2 is moved with a pretension into the resting position (FIG. 1).
The respective motion phases in FIGS. 3 and FIG. 4 make it clear that, on the one hand, the cover 6 for the storage well of the top is pivoted in the arrow direction 14.1 by means of the actuating equipment 15 and, on the other, the folding top 2 is pivoted at 7a by means of the frame 7 for the top in the arrow direction 14.2 during the closing process in such a manner, that the closing part 13 reaches a flap position crossing the path of motion of the locking equipment 12 (FIG. 5), in which the closing part 13 is taken hold of in a well or snap-in opening 17 by the locking equipment 12 and, in this locking position, the folding top 2 and the cover 6 for the storage well of the top can be brought jointly by means of a pivoting/pushing motion into the resting position in which the material 3 of the top is stretched.
With this relationship of the components of the frame 7 and the cover 6 for the storage well of the top, the convertible 1 overall has a fold-free and smooth outer contour in the region of the roof 3 (FIG. 1) and, in the closed state, extensive noise reduction is achievable at high driving speeds. The rear window 4 can be integrated in a fixed and heatable form in the rear region of the roofing 3 so that an advantageously slightly limited field of view is formed only in narrow edge regions 3'.
The side views of FIGS. 2 and 5 illustrate that the cover 6 for the storage well of the top is provided with two catch hooks 19 hereinafter sometimes referred to as catch means, which are disposed at the front edge regions of the cover 6 symmetrically to the longitudinal axis 21 of the vehicle and, engage in each case one anchoring bracket 18 held in the body of the vehicle. With these catch means 19, a further stabilization of the cover 6 for the storage well of the top is achieved in addition to the locking formed in the region of the locking equipment 12 and the closing part 13 and the tightness in the supporting region of the tightening clamp 8 for the top on the cover 6 for the storage well of the top being assured even at high driving speeds.
The partially broken away representation of the rear region of FIG. 4 illustrates that the actuating equipment 15 or actuating means is provided with a reversing lever 23, which is supported on the inside in the region of the longitudinal axis 21 of the vehicle at the rear 22 of the vehicle body and has at a first free leg 24 and a connecting element 25, which is directed to the cover for the storage well of the top and is connected over cross struts 26, 27 extending in each case perpendicularly to the longitudinal axis 21 with parallelogram hinges 28, 29, which, on the one side, are braced at the edge of the rear 22 of the vehicle body and, on the other, hold the cover 6 of the storage well for the top.
In an appropriate embodiment, the reversing lever 23 is provided in the region of its second free leg 24' with a driving element 31, which is constructed as a hydraulic cylinder 31, held on one side by means of a supporting part 32 at the rear 22 of the vehicle body and linked at the other side to a transmission lever 33 (FIG. 6) in such a manner that movement can be initiated in the reversing lever 23 by means of this transmission lever 33. The range of movement of the transmission lever 33 is limited by a stop 34.
In the region of the connecting element 25, the reversing lever 23, in an appropriate embodiment as shown in FIG. 7, has a thrust bolt 24a, guided in a groove 35a, as sliding pairing parts 35, with which, when motion is initiated, a reversible rotary motion can be imparted to the two cross struts 26, 27 and thus, at the same time, an automatic opening and closing motion of the cover 6 for the storage well of the top is attainable. Thus, during pivoting of the reversing lever 24, the thrust bolt 24a is guided in the groove 35a so that the two cross struts 26, 27 are rotated about their longitudinal axes, the reversing lever 24 is pivotable on the vehicle about axis 21' which is parallel to the longitudinal axis of the vehicle, and the transmission lever 33 is pivotable about an axis 21" parallel to the longitudinal axis of the vehicle.
The enlarged detailed representation of the reversing lever 23 of FIG. 6 illustrates that, for initiating the motion, a Bowden wire 36, with which, at the same time, an emergency locking of the components can be achieved, can also be provided on the transmission lever 33. Likewise, it is conceivable that the Bowden wire 36 may be provided at the other end with a driving element (not shown), which can be disposed, to save space, in the side region of the body of the vehicle. In FIG. 7 the hydraulic cylinder 31 is shown pivotably connected to the transmission lever 33 such that when the hydraulic cylinder 31 is operated, the transmission lever 33 is pivoted about axis 21" and moved against the stop 34, whereby the reversing lever 24 is pivoted. FIG. 7 also shows the Bowden wire 36 connected to the transmission lever. Alternatively either the hydraulic cylinder 31 may be used alone or the Bowden wire 36 may be used alone.
The adjusting motion for the cover 6 for the storage well of the top, initiated over the sliding pairing parts 35 in the region of the connecting element 25, is transferred over the cross struts 26, 27 to the parallelogram hinges 28, 29 at the end regions of the cross struts 26, 27 owing to the fact that the end regions of the cross struts 26, 27 are connected with the hinges in the form of the respective hinge mandrels (37) (FIG. 8). The cross struts 26, 27 and the hinge mandrels 37 constitute cross strut means.
The parallelogram hinges 28, 29, for their part, have in the region of the hinge mandrels 37 (FIG. 8) a holding plate 39, which is fixed to the cover 6 (not shown) for the storage well of the top and provided with a connecting lever 40, rising away from this holding plate 39 and having two control levers 41, 42, which are symmetrically disposed at the side. Between the control levers 41, 42, a traction lever 43, which is braced jointly with the two control levers 41, 42 pivotably at the rear 22 of the vehicle body at a bearing, is mounted at the connecting lever 40.
With a parallelogram hinge 16 of such construction, the aforementioned pivoting/pushing motion can be initiated on the cover 6 for the storage well with a high degree of guiding accuracy and a gentle stretching of the folding top 2 can be achieved with little effort in the locking position with the cover 6 for the storage well of the top.
The enlarged, detailed representation of the locking equipment 12 of FIG. 9 illustrates that this equipment is constructed in an appropriate version as a locking well 48 accommodating the closing part 13, constructed as a locking hook 46, over a flap 47. The locking hook 46, supported over a bearing part 49 at the tightening clamp 8 (FIG. 5) for the material of the top, is pressed onto the flap 47 during the locking process and this flap 47, by approaching a microswitch 50, initiates a signal, which is fed back to the driving element 51 (in the form of a hydraulic cylinder) for the frame 7 of the top (FIG. 5) and so ends the closing process. FIG. 2 shows the locking position of the locking hook 46. As further shown in FIG. 9 the locking well 48 has an opening which is engaged by the locking hook 46 when in the locked position.
In addition to the aforementioned locking equipment 12, the cover 6 for the storage well of the top is provided with two catch hooks 19, which are shown in a detailed, enlarged representation in FIG. 9 and can be introduced into an appropriate anchoring bracket 18 in the side region of the rear of the vehicle (FIG. 5). The locking positions of the catch hook 19, shown by the broken lines, illustrate that this catch hook 19 is introduced into a connective engagement during the closing process of the cover 6 for the storage well of the top over a reed 54 having an electric contact maker 53 with a catching bolt 55 at the anchoring bracket 18. With that, the cover 6 for the storage well of the top is positioned in a securing position over the actuating equipment 15 or the locking equipment 12, which is in a functional relationship with this actuating equipment 15, as well as additionally over the catch hooks 19.
At the same time, a signal is generated over the reed 54 by means of an elastically supported adapter 56 in a microswitch 57 and stops the further motion during the closing process of the cover 6 for the storage well of the top or passes on an appropriate release signal over appropriate electrical connection lines 58 for the further control of the cover 6 for the storage well of the top during the opening process.
The retractable folding top operates as follows. With the top 7 up and the cover 6 closed, as shown in FIG. 2, if it is desired to retract the top into the storage well 10, the following sequence of events occur. Initially the actuating means 15 is actuated to move the cover 6 from its closed position (FIG. 1) to its open position (FIG. 3). The actuating means 15 is actuated by actuating the hydraulic cylinder 31 which is pivotably connected to the transmission lever 33 (FIG. 7), and which in turn, is operable to pivot the reversing lever 23 such that actuation of the hydraulic cylinder 31 effects pivoting of the reversing lever 23. Pivoting of the reversing lever 23 effects rotation of the cross struts 26, 27 because the thrust bolt 24a (FIG. 7) on the reversing lever 23 engages the groove 35a on the connecting element 25 which connects the cross struts 26, 27. The ends of the cross struts 26, 27 are connected to the parallel hinges by the respective hinge mandrels 37 (FIG. 8) such that rotation of the cross struts 26, 27 in turn, effects actuation of the parallel hinges.
The parallel hinges have a holding plate 39 (FIG. 8) fixed to the cover 6 and a plate 44 fixed to the vehicle. Thus the cover 6 is movably connected to the vehicle via the parallel hinges. Accordingly, when the cross struts 26, 27 are rotated upon actuation of the hydraulic cylinder 31, as previously described, the rotary motion of the cross struts 26, 27 is transferred to the parallel hinges via the hinge mandrel 37 which are on the ends of the cross struts 26, 27 and which are connected to the parallel hinges 28, 29. Thus the hydraulic cylinder 31 is operable to effect actuation of the parallel hinges so that actuation of the parallel hinges is operable to move the cover 6 between the closed position of FIG. 2, the intermediate position of FIG. 5 and the open position of FIG. 3.
Thus retraction of the top 7 is initiated by actuating the hydraulic cylinder 31 to effect movement of the cover 6 from its closed or locked position of FIG. 2 to the intermediate position of FIG. 5. When moving from the locked position of FIG. 2 to the intermediate position of FIG. 5, the engageable means 12, 13 are released, that is, the closing part 13 on the tightening clamp 8 of the top 7 is disengaged from the locking device 12 on the cover 6 as can be seen in FIG. 5. When the cover 6 moves from the locked position of FIG. 2 to the intermediate position of FIG. 5, the top 7 pivots about axis 7a from the fully closed position of FIG. 2 to the intermediate of FIG. 5 as the hydraulic cylinder 51 shortens. As hydraulic fluid is applied to the hydraulic cylinder 51 and the hydraulic cylinder 51 continues to shorten, the top 7 is further pivoted about axis 7a from the intermediate position of FIG. 5 to the up position of FIG. 3, bearing in mind that the top 7 is released from the cover 6 when the top 7 is in the intermediate position of FIG. 5 so that the top 7 is free to be pivoted to its up position of FIG. 3 by the hydraulic cylinder 51.
Pivoting of the top 7 to the up position of FIG. 3, clears the way for the cover 6 to be pivoted from the intermediate position of FIG. 5 to the fully open position of FIG. 3 by actuating the hydraulic cylinder 31 of the actuating means 15 as previously described. Accordingly, the cover 6 is now clear of the well 10, as shown in FIG. 3, so that the top 7 can now be fully retracted and disposed into the open well. Thereafter, the cover 6 is pivoted by the hydraulic cylinder 31 of the actuating means 15 to its closed position covering the well 10, the closed position being similar to the closed position shown in FIG. 2 but with the top 7 being retracted into the well 10.
When it is desired to put the top up, the reverse procedure is followed. Thus the cover 6 is first pivoted from its closed position to the up position shown in FIG. 3 by the hydraulic cylinder 31 of the actuating means 15 so that the cover 6 is free of the well 10. The top 7 is then withdrawn from the well 10 and disposed in the up position of FIG. 3 by the actuation of hydraulic cylinder 51. Thus the top 7 is clear of the well 10 so that the cover 6 can be pivoted from the up position of FIG. 3 to the intermediate position of FIG. 5. When the top 6 is in the intermediate position of FIG. 5, the cover 7 is pivoted from the up position of FIG. 3 to its intermediate position of FIG. 5. Thereafter further pivoting of the top 7 effects engagement of the engageable means 12, 13 in that the closing part 13 on the frame 8 of the top 7 is engaged by the locking device 12 on the cover 6 so that the top 7 and its frame 8 are locked onto the cover 6 as the cover 6 is moved to its final closed position of FIG. 2 by the hydraulic cylinder 31 of the actuating means 15. | A convertible top for a vehicle includes a folding top frame having top-folded and top-unfolded positions, a storage well in the vehicle, a cover for the storage well, and an actuator operably connected between the cover and the vehicle for moving the cover between a closed position and an open position. The cover when in its closed position covers the storage well, and when in its open position uncovers the storage well. Lockably engageable parts on the cover and the folding top frame are operable to effect locking engagement between the cover and the folding top frame. The actuator includes a cross strut mounted on the cover and having a helical-like groove, and a reversing lever pivotally mounted to the vehicle and having a thrust pin disposed in the groove such that pivoting of the reversing lever rotates the cross strut. The actuator is operable to move the cover in a non-circular path to its closed position as the engagement is effected between the cover and the folding top frame by the engageable parts such that moving of the cover to its closed position by the actuator effects tensioning of the folding top frame. | 1 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of international patent application PCT/CA2014/050789, filed Aug. 19, 2014, which claims the benefit of U.S. patent application 61/867,598 filed Aug. 18, 2013, the entire contents of which are herein incorporated by reference.
TECHNICAL FIELD
[0002] The invention relates to pumps and vehicles equipped for pumping. In particular, the invention relates to manure pumps and amphibious vehicles equipped for pumping liquid manure, such as animal manure contained in a farm lagoon.
BACKGROUND
[0003] Manure produced during animal husbandry, particularly hog and cattle manure, is transferred by washing to a pit or lagoon for storage prior to removal for land application or further processing. During storage, a crust can develop on the surface of the pit or lagoon that must be disrupted prior to or during removal of the manure. Pumps are employed for this purpose with jets that return a percentage of the manure back to the pit or lagoon in the form of a high volume spray to disrupt the crust and recirculate the manure. Pumps for use in recirculating manure from smaller pits are known; however, these pumps are typically suitable for accessing the pit or lagoon from its edge and are connected to a tractor or similar land vehicle for operational power. They are therefore limited in their ability to recirculate manure to the middle of large lagoons, which are becoming increasing common as the size of animal husbandry operations increases.
[0004] Accordingly, there is a need for improved pumps and vehicles equipped for pumping, particularly pumps and vehicles suitable for use with large manure lagoons.
SUMMARY OF THE INVENTION
[0005] According to the invention, there is provided an amphibious pumping vehicle comprising: a floatable vehicle body; ground engaging propulsion structure configured to raise and lower relative to the vehicle body; a fluid pump; a first fluid nozzle configured to direct fluid through the air, the fluid nozzle connected by a fluid conduit to the fluid pump; and, a power source configured to provide power to both the ground engaging propulsion structure and the fluid pump.
[0006] The floatable vehicle body may be in the shape of a mono-hull, a catamaran or a barge. Floatation of the vehicle body may be provided by a displacement hull, pontoon elements, or buoyant elements, for example foam filled buoyant chambers, such as are used for supporting floating docks. The vehicle body may be made using a variety of suitable materials, for example, fiberglass, aluminum, plastics, steel, etc.
[0007] The ground engaging propulsion structure may comprise ground engaging elements of the type suitable for powering a vehicle across wet or muddy terrain. For example, the ground engaging propulsion structure may comprise an endless track or a set of wheels. The set of wheels may comprise two or more wheels, for example four wheels, six wheels or eight wheels. May be provided in pairs with one wheel of each pair disposed on opposite sides of the vehicle. When the vehicle comprises a set of wheels, any number of the wheels may be driven in order to provide propulsion for the vehicle. Although at least two wheels may be driven, it is preferred that at least four wheels are driven. Although the vehicle may be provided with steering structure configured to change direction of one or more pairs of wheels, it is preferred that the wheels are independently driven at variable speeds, allowing them to be fixed in direction relative to the vehicle body. This provides directional control of the vehicle, even in wet or muddy conditions where conventional steering is likely to be ineffective due to sliding of the steerable set of wheels. A variety of drive mechanisms may be used to operate the wheels independently at variable speed; for example, at least one motor may be connected to each wheel that is hydraulically or electrically operable at variable speed. A transmission may alternatively be provided with structure configured to allow each wheel to be operated at variable speeds.
[0008] The ground engaging propulsion structure is configured to raise and lower relative to the vehicle body. Raising and lowering may be provided by telescoping structure or lever structure configured to pivot relative to the vehicle body. The lever structure may comprise a linear actuator that is driven, for example hydraulically, to cause pivoting of the lever arm relative to the vehicle body and thereby raise or lower the wheels. Each wheel is preferably raised or lowered at the same time. Alternatively, the lever structure may comprise a planetary drive that is either mechanically or hydraulically powered to cause pivoting of the lever arm.
[0009] The vehicle further comprises a power source configured to provide power to both the ground engaging propulsion structure and the fluid pump. The power source may be self-contained on the vehicle or may be linked to shore. For example, the power source may comprise an internal combustion engine, a fuel-cell, electric batteries, etc. The power source may comprise an electric motor that may be driven from shore via an electrical cable. The power source may be connected to a generator for supplying electrical power to electrical systems on board the vehicle. The power source may be connected to a hydraulic pump for supplying hydraulic fluid pressure to hydraulic systems on board the vehicle. The power source may be connected to the fluid pump hydraulically, electrically, or via a mechanical drive. A single power source may be used to provide power to all vehicle systems, including the fluid pump. In one embodiment, the power source is an internal combustion engine that is connected to the fluid pump and a hydraulic pump via a mechanical drive. The mechanical drive may comprise a gearbox to provide an appropriate rotational speed for the fluid pump. The mechanical drive may comprise a gearbox to provide an appropriate rotational speed for the hydraulic pump. The fluid pump and hydraulic pump may be operated at the same or different rotational speeds.
[0010] The fluid pump may comprise a pump housing configured for immersion within the fluid. The pump housing may comprise a bottom fluid inlet and at least two tangential fluid outlets. A greater number of tangential fluid outlets may be provided, for example three fluid outlets. The tangential fluid outlets may be combined into a single fluid conduit for directing the combined output of the fluid pump to a desired location. The vehicle may comprise structure configured to cause raising and lowering of the fluid pump, especially the fluid pump housing, relative to the vehicle body. For example, a hydraulically or electrically driven linear actuator may be provided on the vehicle and configured to raise and lower the fluid pump. This may be accomplished via a telescoping structure or a lever structure of the vehicle. The tangential fluid outlets may be equipped with flexible or telescoping connections to the single fluid conduit. Lowering the fluid pump for immersion into the fluid obviates the need for priming the fluid pump, which can be problematic when the fluid is manure comprising solid materials that can plug the pump or priming structure. Immersion of the pump also simplifies intermittent operation of the pump, due to eliminating potential loss of prime, and reduces the need for pump maintenance.
[0011] The vehicle comprises a first fluid nozzle configured to direct fluid through the air. The fluid nozzle is connected by fluid conduit to the fluid pump. The fluid conduit connecting the fluid nozzle to the fluid pump may comprise the single fluid conduit that is connected to the tangential fluid outlets of the pump. The vehicle may further comprise a plurality of fluid nozzles comprising the first fluid nozzle and at least one second fluid nozzle connected to the fluid conduit. The first fluid nozzle may comprise a front nozzle and the second fluid conduit may comprise the rear nozzle or a pair of rear nozzles. The plurality of fluid nozzles may comprise at least two side fluid nozzles on opposite sides of vehicle connected to the fluid conduit. The at least two side fluid nozzles may comprise a pair of fluid nozzles on opposite sides of the vehicle connected to the fluid conduit; thus, the at least two side fluid nozzles may comprise a total of four fluid nozzles. The vehicle may further comprise valve structure configured to proportion fluid flow between the plurality of fluid nozzles. The valve structure may comprise a valve corresponding to each fluid nozzle. The valve corresponding to each fluid nozzle may be actuatable, for example hydraulically or electrically. The valve structure may be actuatable remotely.
[0012] The plurality of fluid nozzles and the valve structure may cooperate to provide directional control, motive power, or a combination thereof for the vehicle when floating. For example, by closing valve structure associated with the fluid nozzle(s) on the right side of the vehicle, fluid flow is directed to the nozzle(s) on the left side of the vehicle, causing the vehicle to turn to the right. In one embodiment, steering is achieved solely by cooperation of the plurality of fluid nozzles and the valve structure; accordingly, the vehicle does not comprise a rudder. In one embodiment, movement of the vehicle while floating is achieved solely by cooperation of at least the second fluid nozzle and the valve structure; accordingly, the vehicle does not comprise a propeller.
[0013] One or more fluid nozzles may comprise adjustment structure that is powered and configured to adjust an angle of the fluid nozzle relative to the floatable vehicle body. For example, the first fluid nozzle may comprise first adjustment structure and the second fluid nozzle(s) may comprise second adjustment structure, each adjustment structure configured to adjust an angular orientation of its respective fluid nozzle(s) in a vertical and/or horizontal plane. In one embodiment, both the first fluid nozzle and the second fluid nozzle(s) are adjustable in a vertical plane. The second fluid nozzle(s) is/are adjustable in the vertical plane by an amount sufficient to cause forward or backward movement of the vehicle when floating. In other words, the second fluid nozzle(s) is/are adjustable to point at least partially toward the front of the vehicle at least partially toward the rear of the vehicle. The second fluid nozzle(s) may be configured to direct fluid through the air in a substantially downward direction. The first fluid nozzle may be configured to direct fluid through the air in a substantially upward direction. The side fluid nozzle(s) may be configured to direct fluid through the air in a substantially downward direction. One or more side fluid nozzle(s) may comprise adjustment structure configured to adjust an angular orientation of its respective side fluid nozzle(s) in a vertical plane.
[0014] The location of at least the ground engaging propulsion structure, the power source and the fluid pump may be selected to provide a desired location for a center of gravity of the vehicle. The desired location for the center of gravity of the vehicle may be selected to improve handling characteristics of the vehicle while floating. The center of gravity may be located along the longitudinal centerline of the vehicle. The center of gravity may be located substantially in the middle of the vehicle, for example at an intersection of longitudinal centerline of the vehicle and the transverse centerline of the vehicle. The center of gravity may be located rearward of the transverse centerline of the vehicle. The center of gravity may be located forward of the transverse centerline of the vehicle. Thus the ground engaging propulsion structure, power source, and fluid pump cooperate together to improve handling characteristics of the vehicle.
[0015] The vehicle may comprise remote control structure configured to cause the vehicle to be remotely controllable by an operator remote from the vehicle. The vehicle may be remotely controllable by an operator remote from the vehicle when the vehicle is ground engaging and when the vehicle is floating. The remote control structure may comprise a wireless transmitter and a wireless receiver. The remote control structure may be configured to control the speed and or direction of the vehicle when ground engaging and when floating. The remote control structure may be configured to control an amount of fluid flow from at least the first nozzle. The remote control structure may be configured to control an angular orientation of at least the first nozzle relative to the vehicle body. The remote control structure may be configured to control an amount of fluid flow from at least the second nozzle(s). The remote control structure may be configured to control an angular orientation of at least the second nozzle(s) relative to the vehicle body. The remote control structure may be configured to control the valve structure in order to proportion fluid flow between the plurality of fluid nozzles. The remote control structure may be configured to control rotational speed of the fluid pump. The remote control structure may be configured to raise and lower the fluid pump. The remote control structure may be configured to raise and lower the ground engaging propulsion structure. The remote control structure may be configured to start and stop the power source.
[0016] Further features of the invention will be described or will become apparent in the course of the following description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] In order that the invention may be more clearly understood, embodiments thereof will now be described in detail by way of example, with reference to the accompanying drawings, in which:
[0018] FIG. 1 shows a perspective view of an embodiment of the vehicle with wheels lowered;
[0019] FIG. 2 shows another perspective view of the vehicle with wheels raised;
[0020] FIG. 3 shows a perspective view of the underside of the vehicle; and,
[0021] FIG. 4 shows a perspective view of a set of wheels of the vehicle from the underside of the vehicle;
[0022] FIG. 5 shows a perspective view of the first fluid nozzle of vehicle;
[0023] FIG. 6 shows a perspective view of a second fluid nozzle of the vehicle;
[0024] FIG. 7 shows a perspective view of a mechanical drive connecting the power source of the vehicle to the fluid pump and a hydraulic pump of the vehicle;
[0025] FIG. 8 shows a perspective view of the fluid pump from the underside of the vehicle.
DETAILED DESCRIPTION
[0026] In describing the figures, like features are referred to by like reference numerals. Although not all features indicated on a particular drawing are necessarily described with reference to that drawing, all of the features are described with reference to at least one of the drawings.
[0027] Referring to FIGS. 1-3 , an amphibious vehicle comprises a vehicle body 1 incorporating buoyant elements 2 . The buoyant elements comprise flotation tanks of the type that may be foam filled and used, for example, in the construction of floating docks. The vehicle comprises a ground engaging propulsion structure comprising two sets of wheels 3 , 4 . Each wheel is rotatably mounted to lever structure 5 that is pivotally attached to the vehicle body. Each lever structure 5 is driven by a hydraulic actuator 6 that is operable to cause raising and lowering of the wheels 3 , 4 by pivoting of the lever structure 5 . A power source 7 comprising an internal combustion engine, for example a diesel engine, is mounted to the vehicle body. A mechanical drive 8 connects the power source 7 to the fluid pump 9 and a hydraulic pump 10 that is used to provide hydraulic system fluid pressure for the vehicle.
[0028] The fluid pump 9 comprises a pump housing 18 with three tangential fluid outlets 19 that are combined into a single fluid conduit 20 . The single fluid conduit 20 is then split into left side 21 and right side 22 fluid conduits which connect at the front and rear of the vehicle to form a complete circuit. The fluid pump 9 is thus fluidically connected to all fluid nozzles of the vehicle via the fluid conduits 20 - 22 .
[0029] A first fluid nozzle 11 is provided at a front of the vehicle. The first fluid nozzle 11 comprises first articulation means 12 that is hydraulically powered to cause the nozzle to change angular orientation relative to the vehicle body 1 in a vertical plane. A pair of second fluid nozzles 13 is provided at a rear of the vehicle. The second fluid nozzles 13 comprise a second articulation means 14 that is hydraulically powered to cause the nozzles to change angular orientation relative to the vehicle body 1 in a vertical plane. The first and second fluid nozzles are part of a plurality of fluid nozzles of the vehicle. The plurality of fluid nozzles further comprises side fluid nozzles 16 , 17 on opposite sides of the vehicle. A pair of left side fluid nozzles 16 and a pair of right side fluid nozzles 17 are provided.
[0030] Valve structure comprising a valve 15 corresponding to each fluid nozzle 11 , 13 , 16 , 17 is also provided. The valves 15 are powered and operable to open or close. The valves 15 may be opened fully or partially to proportion flow between the plurality of fluid nozzles. Cooperation between the valves 15 and the plurality of fluid nozzles is used to provide directional control and motive power for the vehicle while floating. For example, proportioning fluid flow from the right side fluid nozzles 17 to the left side fluid nozzles 16 causes the vehicle to turn to the right will floating. Similarly, fluid flow may be proportioned between the first fluid nozzle 11 and the second fluid nozzles 13 to cause the vehicle to move forward or backward. By rotating the second fluid nozzles 13 fully downwardly and then up toward the front of the vehicle using the second articulation means 14 , the vehicle may also be directed rearward and/or slowed in its forward movement speed. Thus, the combination of proportioning flow between the plurality of fluid nozzles using the valve structure and/or articulating the nozzles may be used to control forward, rearward, left and right movement and speed of the vehicle. The flow rate of the fluid pump 9 may also be adjusted to enhance directional and speed control via the plurality of nozzles while floating.
[0031] Referring additionally to FIG. 4 , each wheel of the front set of wheels 3 is rotatably attached to its corresponding lever 5 by a spindle 23 . Fixedly mounted to lever 5 is a bracket 24 supporting a pair of hydraulic motors 25 . Each hydraulic motor 25 has an output gear (not shown) that is engaged with a drive gear 26 . The drive gear 26 is fixedly attached to a rim 27 of each wheel 3 concentric with the spindle 23 . Referring to the right side wheel of the set of wheels 3 (showing an interior of the rim 27 ), operation of the hydraulic motors 25 in a clockwise direction causes the drive gear 26 to rotate in a counterclockwise direction, moving the vehicle forward. Reversing the direction of operation of the hydraulic motors 25 causes the vehicle to move rearward. By increasing the rotational speed of the hydraulic motors 25 on the right side relative to the motors 25 on the left side, the vehicle is caused to turn to the left. The motors 25 connected to the rear set of wheels 4 work in a similar manner to those described for the front set of wheels 3 . Thus, directional and motive control of the vehicle (forward/reverse) while on land is controlled by varying the relative speed and rotational direction of the hydraulic motors 25 .
[0032] Turning now to FIG. 5 , the first fluid nozzle 11 is able to change angular direction in a vertical plane relative to the vehicle body 1 through operation of a powered first articulation means 12 . The first articulation means 12 comprises a hydraulic first articulation cylinder 28 that is coupled to a four bar linkage 29 . The four bar linkage serves to amplify the effective stroke length of the first articulation cylinder 28 to cause the nozzle to move through a larger degree of motion in the vertical plane than if the linkage 29 were not present. The first fluid nozzle 11 is connected to the fluid conduits 21 , 22 via a flexible conduit 30 that permits articulation of the nozzle. Valves 15 are provided to proportion flow to the first fluid nozzle in a manner as described previously.
[0033] Referring to FIG. 6 , the second fluid nozzles 13 are connected to the fluid conduits 21 , 22 by articulation means 14 that comprises a hydraulic second articulation cylinder 31 mounted to the vehicle body 1 and connected to a rotatable conduit section 32 . Actuation of the second articulation cylinder 31 causes the rotatable conduit section 32 to rotate relative to the first and second fluid conduits 21 , 22 . The second fluid nozzles 13 are provided on rotatable conduit section 32 and thus rotate with the conduit section 32 upon actuation of the articulation cylinder 31 . This causes the nozzles 13 to change angular orientation relative to the vehicle body 1 in a vertical plane. The geometry of the second articulation cylinder 31 and the rotatable conduit section 32 is such that the nozzles 13 may be rotated fully downwardly and then upwardly towards the front of the vehicle. This allows an operator to change the amount of forward movement to slow or even reverse forward movement of the vehicle. When operated in conjunction with the valves 15 , the nozzles 13 and second articulation structure 14 provide a high degree of control over forward and reverse movement of the vehicle.
[0034] Referring to FIG. 7 , the power source 7 comprises an internal combustion engine connected to a mechanical drive 8 that delivers power to the pump 9 (not shown in FIG. 7 ) and also to the hydraulic pump 10 that is used to provide hydraulic fluid pressure to the vehicle's hydraulic systems. A transmission is provided within the mechanical drive 8 that allows the rotational speed of the fluid pump 9 to be adjusted independently of the rotational speed of the hydraulic pump 10 . The power source 7 is thus mechanically connected to both the fluid pump 9 and the hydraulic pump 10 .
[0035] Referring to FIG. 8 , the fluid pump 9 comprises a pump housing 18 comprising three tangential fluid outlets 19 that are connected via flexible pump outlet conduits 33 to a combiner 34 that is used to combine the fluid output of the tangential fluid outlets 19 into the single conduit 20 . A pump actuation cylinder 35 is provided to cause raising and lowering of the pump 9 and especially the pump housing 18 relative to the vehicle body 1 . A telescoping pump support structure 36 is provided for use in combination with the pump actuation cylinder 35 . A mechanical drive shaft (not shown) runs through the telescoping pump support structure 36 to provide power to the pump impeller 37 . When powered, the impeller 37 draws the fluid to be pumped through an enlarged bottom fluid opening 38 of the pump housing 18 . By immersing the pump housing 18 in the fluid, fluid is allowed to enter the pump housing, thereby obviating the need for priming the pump. Raising the pump 9 via the pump actuation cylinder 35 and telescoping pump support structure 36 allows the vehicle to exit the lagoon (or similar fluid reservoir) without damaging the pump. Thus, these structures cooperate with the ground engaging propulsion structure to allow the vehicle to operate on land.
[0036] An example of a pump 9 suitable for use with the vehicle is disclosed in co-pending U.S. patent application Ser. No. 13/038,189 filed Mar. 1, 2011, entitled Pump for Immersion Within a Fluid Reservoir, which is incorporated herein by reference.
[0037] The location of at least the ground engaging propulsion structure, the power source and the fluid pump are selected to provide a desired location for a center of gravity of the vehicle. The desired location for the center of gravity of the vehicle is selected to improve handling characteristics of the vehicle while floating. The center of gravity is located along the longitudinal centerline of the vehicle, substantially in the middle of the vehicle.
[0038] A remote control structure 40 comprises an antenna configured to cause the vehicle to be remotely controllable by an operator remote from the vehicle. The remote control structure comprises a wireless transmitter used by the operator and a wireless receiver on the vehicle. The wireless receiver interfaces with a hydraulic control center on the vehicle to permit control of hydraulically operated components, such as hydraulic cylinders, valves, motors, etc. This allows the operator to control vehicle speed and direction on land or when floating, to raise the wheels and to change the angular orientation of the first and second fluid nozzles. A wireless engine starter is provided to control operation of the internal combustion engine used as a power source. A set of hydraulic controls is optionally provided to modulate engine speed and/or fluid pump rotational speed. Thus, a variety of functions may be controlled remotely that allow the vehicle to operate on land or when floating.
[0039] In operation, an operator uses the remote controls to maneuver the vehicle to the lagoon entrance, drive the vehicle into the lagoon, raise the ground engaging propulsion structure (wheels), lower the fluid pump, begin pumping fluid with the fluid pump through the fluid conduits and selectively open at least the second fluid nozzles to cause the vehicle to move out on to the surface of the lagoon. The valves associated with the side fluid nozzles may also be opened or closed to provide directional control of the vehicle on the lagoon. Once the vehicle is in the desired position, the valves associated with the first fluid nozzle are opened and the first articulation structure is used to position the first fluid nozzle at a desired angular orientation relative to the vehicle body. This is generally an upward orientation so that the fluid is sprayed widely to break crusts of material floating on the surface of the lagoon. In this manner, fluid is recirculated and directed to desired locations in the lagoon. As fluid is emptied from the lagoon, the floating vehicle is permitted to lower with the fluid level. When the lagoon has been sufficiently emptied, the operator is able to reverse the foregoing process in order to maneuver the vehicle to the lagoon exit, lower the wheels, and drive the vehicle up the muddy bank out of the lagoon.
[0040] The novel features will become apparent to those of skill in the art upon examination of the description. It should be understood, however, that the scope of the claims should not be limited by the embodiments, but are intended by the inventor to be given the broadest interpretation consistent with the wording of the claims and the specification as a whole. | An amphibious pumping vehicle comprising: a floatable vehicle body; ground engaging propulsion structure configured to raise and lower relative to the vehicle body; a fluid pump; a first fluid nozzle configured to direct fluid through the air, the fluid nozzle connected by a fluid conduit to the fluid pump; and, a power source configured to provide power to both the ground engaging propulsion structure and the fluid pump. The vehicle is particularly well suited to pumping and recirculating fluid within manure lagoons and is able to be driven up out of the lagoon when the lagoon level has been lowered. | 1 |
FIELD OF INVENTION
The present disclosure relates to a kit for the construction of a finished product, particularly knitted products. The present disclosure also relates to methods of packaging the kit for an effective presentation to the purchaser.
BACKGROUND
Knitting and crocheting hand-made garments is a custom that is often passed down from generation to generation, providing a skill that can be used for a lifetime. While hand-made clothing is no longer a necessity for many people, many still enjoy the hobby of knitting garments, blankets, or any number of other items in a large variety of patterns and colors.
There continues to be an opportunity to package and combine a novel set of elements to attract a potential customer with a user friendly design that would appeal to the creator of the finished product, a stitcher, as well as the recipient athe finished product.
SUMMARY
This disclosure includes a kit for creating a knitted garment, such as a hat. The kit can include yarn, a topper, a stabiliser, and instructions for creating the garment from the yarn, topper, and stabilizer.
This disclosure also includes a method for packaging a kit of items used to knit a garment, such as a hat. The method can include wrapping yarn into a generally spherical shape. The method further comprises placing a wrapper, the wrapper being printed with a set of instructions, adjacent to the yarn such that an aperture through the wrapper generally corresponds with an axis through the middle of the wrapped yarn. The method may also include mounting a topper upon the wrapped yarn by passing at least a portion of the topper through the aperture of the wrapper and generally though the center of the wrapped yarn. The method may include attaching a stabilizer to the wrapper, encircling the yarn with the wrapper, and connecting together the ends of the wrapper to complete the package.
These and other aspects of the present invention will become apparent to those skilled in the art after a reading of the following description of the preferred embodiments, when considered in conjunction with the drawings, it should be understood that both the foregoing general description and the following detailed description are explanatory only and are not restrictive of the invention as claimed.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a kit according to embodiments of the present disclosure having been packaged by methods of the present disclosure.
FIG. 2 is an unpackaged kit according to embodiments of the present disclosure.
FIG. 3 is a detailed view of the yarn according to embodiments of the present disclosure.
FIG. 4 shows instructions according to an embodiment of the present disclosure.
FIG. 5 shows a final garment created using the kit according; to embodiments of the present invention.
FIG. 6 shows a step of the packaging process according to embodiments of the present disclosure.
FIG. 7 shows another step of the packaging process according to embodiments of the present disclosure.
FIG. 8 shows yet another step of the packaging process according to embodiments of the present disclosure.
The foregoing and still other objects and advantages of the present invention will be more apparent from the following detailed explanation of embodiments of the invention in connection with the accompanying drawings.
DETAILED DESCRIPTION
Exemplary embodiments of this disclosure are described below and illustrated in the accompanying figures, in which like numerals refer to like parts throughout the several views. The embodiments described provide examples and should not be interpreted as limiting the scope of the invention. Other embodiments, and modifications and improvements of the described embodiments, will occur to those skilled in the art and all such other embodiments, modifications and improvements are within the scope of the present invention. Features from one embodiment or aspect may be combined with features from any other embodiment or aspect in any appropriate combination. For example, any individual or collective features of method aspects or embodiments may be applied to apparatus, product or component aspects or embodiments and vice versa.
Turning to the figures, FIG. 1 shoves a kit 1 packaged according to embodiments of the present disclosure. The preferred elements of the kit 1 are more clearly understood from the layout of FIG. 2 . FIG. 2 shows the kit 1 having yarn 10 that can be wrapped into a generally spherical shaped ball, a topper 20 , a stabilizer 30 and a wrapper 40 .
The yarn 10 is shown in a relatively unraveled or unwrapped configuration in FIG. 3 . As seen in FIG. 3 , the yarn 10 may include a plurality or first segments 12 , a plurality of second segments 14 , and a plurality of third segments 16 . The yarn 10 may be a single continuously attached length with the segments joined together at joining locations 18 , so that a stitcher, the person who creates the final garment, does not have to change spools when knitting the final garment 100 (see FIG. 5 ). The segments are shown as joined together in the following pattern: a first segment 12 , a second segment 14 , a third segment 16 , another first segment 12 , another second segment 14 , another third segment 16 , and a final first segment 12 , as seen in FIG. 3 . As a result, the yarn 10 starts and ends with a first segment 12 . This way the stitcher could start the project from either end of the yarn 10 . In other embodiments the total number of segments may vary. In other embodiments, the pattern of segments may vary. While FIG. 3 illustrates three unique segment types, there could be more or fewer segment types. As should be clear from FIG. 3 , the length of each segment varies and may be predetermined based upon the knitting pattern being used and the desired completed appearance of the final garment 100 .
The yarn 10 should be selected from materials suitable. for use with the final garment 100 . If a hat is desired, warm, soft materials or blends may be used. As one example, a blend of 78% acrylic and 22% nylon may be used. The yarn 10 may also vary in length based on the size of the final garment 100 . In one example, the yarn 10 is approximately 90 meters in length.
In the illustrated, non-limiting example, the first segments 12 have a first color pattern and texture; the second segments 14 have a second color pattern and second texture. In one example shown, the first and second color patterns are different, but the first and second textures are substantially the same. Further, the third segments 16 have a third color pattern and a third texture. In the illustrated embodiment, the third segments 16 combine the first and second colors. The third texture may be felted to provide the third texture with a feel distinct from the first and second textures.
Turning back to FIG. 2 , the topper 20 can include an ornament 22 . and the retention 24 . In a preferred embodiment the retentioner 24 comprises a pair of attachment straps as shown in FIG. 2 . The ornament 22 may take any number of shapes and configurations. Preferably, the ornament 22 is a three-dimensional pre-made plush representation of an animal or other item, such as a sports ball. Generally, the ornament 22 is not capable of being created by knitting techniques using the yarn 10 .
The retentioner 24 is connected to the ornament 22 and used for attaching the ornament 22 to the final garment 100 . The retentioner 24 may be a variety of materials. The retentioner 24 of the present embodiment is ribbon. The retentioner 24 should be of sufficient length to secure the topper 20 to the final garment 100 , and should be of sufficient length to retain the topper 20 as part of the packaged kit 1 shown in FIG. 1 . Where straps are used, the retentioner 24 could include two or more straps. In other embodiments, the retentioner 24 could be a button, or equivalent structure, for passing through a smaller or differently shaped opening to provide retention.
Stabilizer 30 may be used to secure the topper 20 to the final garment 100 . The use of the stabilizer 30 assists with maintaining the ornament 22 in a generally upright orientation when the final garment 100 is being worn on someone's head. The stabilizer 30 may be provided with one or more through-holes 32 through which the retentioner 24 may be pulled and securely tied in a removable fashion. The number of through-holes may correspond with number of straps of the retentioner 24 . The one or more through-holes 32 may be grooves on the edge of the stabilizer 30 to clip a portion of the retentioner 24 . The stabilizer 30 may be disk shaped to be round and relatively flat for a comfortable fit. The stabilizer 30 could be other shapes as well, which provide the function of positioning the retentioner 24 . Other shapes or structures include annular, e-clip, hexagonal, rectangular, etc. The stabilizer 30 may be formed from foam or other materials that avoid discomfort to the wearer of the final garment 100 .
The wrapper 40 can be printed with instructions 42 on an inner surface thereof. Alternatively, the instructions 42 may be printed on an outer surface of the wrapper 40 . In even other embodiments, the instructions 42 may be provided separate from the wrapper 40 . The outer surface or the wrapper 40 may be printed with labels or other product identification features. The instructions 42 may include the written or visual description of a pattern for knitting the yarn 10 into a body 110 of a final garment 100 .
An example of instructions 42 for the body 110 may be:
Using a US X. Y-inch circular needle, cast on A stitches. Place a marker and join, being careful not to twist the stitches. Work K 2 , P 2 rib for B rounds. Work the next C rounds in stockinette stich. On the last round, place a maker every B rounds. A, B and C may be predetermined quantities or varied quantities based on the desired size of the final garment 100 (see FIG. 5 ). Switching to double pointed needles as needed, knitting to 2 stitches before the first marker, K 2 tog. Repeat at each marker until 6 stiches remain to form a 6-point spiral. To finish the body of the garment, allowing 8 inches, cut yarn and thread onto a yarn needle. Draw the yarn through the remaining live stitches twice and secure, Weave in ends.
The instructions 42 may also include a visual or written description for securing the topper 20 to the body 110 . A sample set of visual instructions 42 for securing the topper 20 are shown in FIG. 4 .
An example of a final garment 100 having a body 110 adorned with the topper 20 is shown in FIG. 5 .
Moving to FIGS. 6-8 , a set of steps is shown for packaging the kit 1 as seen in FIG. 1 . The first step in packaging the kit 1 requires providing or obtaining each of the items laid out in FIG. 2 . This may include taking a length of yarn 10 and wrapping said yarn 10 into the ball shown in FIG. 2 .
FIG. 6 shows the step of securing the stabilizer 30 to the inner surface of the wrapper 40 . Adhesive may be used to secure the stabilizer 30 in place. The stabilizer 30 should be securely held in place so that the stabilizer 30 does not inadvertently fall from the packaged kit 1 . The stabilizer 30 may be securely packaged in other ways, such as being pre-engaged with the retentioner 24 .
FIG. 7 shows the placement of the wrapper 40 with respect to the yarn 10 . The aperture 44 through the wrapper 40 should be disposed relative to the wrapped yarn 10 such that an axis through the center of the wrapped yarn 10 would pass through the aperture 44 .
FIG. 8 shows the placement of the topper 20 onto the package. The retentioner 24 may be run through the aperture 44 of the wrapper 40 and down approximately through the center of the wrapped yarn 10 . As should be clear from the comparison of FIG. 8 with FIG. 1 , the package may be completed by encircling the yarn 10 with the wrapper 40 , and securing the ends of the wrapper 40 together. The ends may be connected by adhesive. The ends may be connected by other means such as a tab and a corresponding slot. In some embodiments, at least a portion of the retentioner 24 may be entrapped between the connected ends of the wrapper 40 to assist with securing the topper 20 as part of the packaged kit 1 .
Although the above disclosure has been presented in the context of exemplary embodiments, it is to be understood that modifications and variations may be utilized without departing from the spirit and scope of the invention, as those skilled in the art will readily understand. Such modifications and variations are considered to be within the purview and scope of the appended claims and their equivalents. | The disclosure herein relates to a kit for creating a knitted garment such as a hat. The kit includes a length of yarn, a topper, a stabilizer, and optionally instructions for creating the garment from the yarn, topper and stabilizer. A method of packaging the kit for an effective presentation to the purchaser is also provided. | 1 |
BACKGROUND OF THE INVENTION
This invention relates to apparatus for reeling web- or strand-like material.
There are many instances where a manufacturing or treatment machine for an elongate web- or strand-like material ends in a re-reeling of the material. An example is a printing machine for continuous stationery. It is important, in the latter case in particular, that the printed paper web should be uniformly wound i.e. with controlled tension, on the reel. Otherwise subsequent handling of the web e.g. accurate interleaving of a number of zig-zag folded webs, may be possible.
In the past, even the use of a set of dancer rolls to absorb changes in the web speed compared with the reeling speed, or the use of a constant torque drive to the final reel, have not provided satisfactory re-reeling. This is because of the high speed of the web and the consequent inability of the dancer rolls and the drive to adjust quickly enough.
SUMMARY OF THE INVENTION
It is an object of the invention to overcome or at least reduce the problems mentioned above.
According to the invention, there is provided an apparatus for reeling web or strand like material comprising sensing means for sensing the tension in the material to be reeled, a non-driven control cylinder separate from said sensing means and with a non-slip surface around which the material is to pass, brake means acting on said control cylinder and control means responsive to said sensing means to provide actuation of said brake means in dependence thereon.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will now be described in greater detail, by way of example, with reference to the drawings, in which:
FIG. 1 shows the schematic layout of a reeling apparatus according to the invention, and
FIG. 2 shows a side elevation of a reeling apparatus operating as in FIG. 1.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
A web of paper 10 emerges from a printing machine (not shown) and is reeled onto a final reel 11. Between the printing machine (or any other processing machine) and the final reel, the paper web passes through a dancer roll assembly 12 and around a control cylinder 13. The latter is freely rotatable in friction-minimising bearings and has a cylindrical surface which is prepared or coated so as to inhibit slipping of the paper web passing around it. The rotation of the cylinder 13 can be controlled by a brake 14, which is itself controlled by the position of the dancer roll of assembly 12 through control means indicated at 15. This brake 14 is preferably an electrically actuated magnetic particle brake.
The final reel 11 is driven by an electric motor which is, for example, of settable but constant torque, e.g. the motor is a constant torque motor whose torque can be set. If the reel 11 is prevented from rotating for any reason, the electric motor slips electrically.
By means of this arrangement it becomes possible to greatly improve the reeling, and additionally to isolate the tension in the final reel from the operating tension in the printing machine and vice versa.
In normal operation, the final reel 11 is driven at its set torque by the electric motor. The dancer roll is in the region of its lowest position and the control cylinder is rotating freely.
There is no slip between the web and the friction surface of the control cylinder.
If now the printing machine slows down, for example, the dancer roll tends to move upwards, since the inertia of the final reel and the constant torque drive of the motor will continue to draw the web even though it is no longer issuing so fast from the machine. As the dancer roll moves up, it adjusts the brake 14 through the control 15 so that the cylinder 13 and the web 10 are smoothly braked against the pull of the final reel 11. The tension in the web being reeled cannot increase above the level set by the predetermined maximum torque of the drive motor, and if the cylinder 13 is braked more than a certain amount, the motor slips. Even if the dancer roll moves right to the top of its travel, so that it cannot any longer perform its normal buffer function, the cylinder 13 will be braked to a standstill without any harm to the web, without the reeling tension being affected, and without the reeling tension being `reflected back` into the printing machine.
Once the supply of the web from the machine speeds up (or starts again), the dancer roll starts to drop, and the brake 14 starts to be released. The web starts to increase its speed (or starts to move) and the reeling eventually returns again to normal.
In practice, this control sequence occurs very frequently and very rapidly, constantly adjusting the flow of the web to the final reel in accordance with the supply from the printing machine. The result is an almost complete isolation of the reeling process from the printing (or other handling) process, as desired, although both remain continuous and simultaneous.
Turning now to FIG. 2, which shows more practical details, the same reference numerals are applied to parts which correspond to those in FIG. 1. The apparatus comprises a frame 20, the side members 21 of which support the various rolls and cylinders. The web 10 passes through substantially the same path as was described for FIG. 1.
The web 10 arrives in the apparatus by way of a first fixed roll 21 and passes upwards therefrom to the first fixed roll 22 of the dance roll assembly 12. From the roll 22, the web 10 proceeds downwardly, around the first dancer roll 23, upwardly to the second fixed roll 24, upwardly again to the second dancer roll 25 and upwardly again to the third stationary roll 26. The dancer rolls 23 and 25 are supported at each end in bearings in a framework 28 which moves upwardly and downwardly on a post 29. The framework 28 is supported by an endless chain 30. The chain 30 extends around sprockets 31 and 32, the uppermost 31 of which is coupled to a rotary potentiometer indicated diagrammatically at 33. The latter is connected electrically by a line indicated at 50 so as to control the electrically actuated magnetic particle brake 14. At and near the lowermost position of the dancer roll frame 28, the electrical supply determined by the potentiometer 31 is such as to reduce the effect of the brake 14 to a minimum residual level; as the dancer roll frame 28 rises, the braking effect is steadily increased, until in the uppermost position the brake 14 is fully applied.
The brake 14, mounted on a cross beam 48, is a magnetic particle brake which is linked by a belt 40 to the control cylinder 13. The web 10 is deflected by the fixed rollers 26 so that it is wrapped around at least half the circumference of the cylinder 13 to a further fixed roller 41. The latter has an outer cylindrical surface which is rendered rough by metal spraying. There is thus no slip possible between the web 10 and the cylindrical surface.
The web finally passes by way of yet a further fixed roller 42 to the final reel 11, which is supported in bearings 49 and is driven by a motor 43. The latter is designed to deliver a constant, pre-settable torque through the chain drive 44. On its own, this would not lead to a constant tension in the reeled web, because the torque acts on a constantly increasing lever arm as the radius of the reel increases. If desired, a control sensor 45 may be provided, biassed (here, by gravity) to contact and sense the radius of the reel, and its angular position can be used directly or indirectly to pre-set the torque of the motor 43. Alternatively manual control can be used.
A lifting device 46, operated by a hydraulic cylinder 47 is used to lift a completed reel from the bearings 42.
The operation of this apparatus is in principle exactly as described with reference to FIG. 1. The principle can be applied to the reeling of many materials other than paper, e.g. textiles, cables, threads and tapes.
The brake may be of any desired type, operable for example by mechanical, electrical, hydraulic or pneumatic means. The control cylinder, may have any convenient frictional surface. The sending of the position of the dancer roll may be affected by any other suitable means, e.g. by photoelectric sensing means, or inductive field sensing. Indeed the roller itself may be omitted and only the position of the loop of the web detected.
The control cylinder may have a counter roller to prevent slipping of the web. | An apparatus for reeling web or strand-like material comprises sensing means for sensing the tension in the material to be reeled, a separate non-driven control cylinder which has a non-slip surface around which the material is to pass, the control cylinder having brake means acting thereon under control means responsive to the sensing means. | 1 |
RELATED APPLICATIONS
[0001] This application claims priority to Provisional Application Ser. No. 62/263,497, filed on Dec. 4, 2015 and to Provisional Application Ser. No. 62/379,420, filed on Aug. 24, 2015 by the same inventor, both disclosures of which are fully incorporated by reference herein.
FIELD OF THE INVENTION
[0002] 1. Background
[0003] This invention relates to a system and method (including related software) for making one or more toys become “more” interactive depending on the time of day and relative distance from a reader device. More particularly, reactions from the toy (or toys) will purposefully vary depending on chronological input (time of day), signal strength and frequency of reader interactions.
[0004] 2. Relevant Art
[0005] A representative prior art system was that shown and described in Giedgowd et al. U.S. Published Patent Application No. 20130059284. However, that disclosure merely calculated the time that an RFID tag entered the range of a reader and the length of time that has been around the toy. The present invention far exceeds the interactive nature of that earlier reference.
BRIEF SUMMARY OF THE INVENTION
[0006] It is a principle object of this invention to bring life and “intelligence” to toys and objects by reactions with a reader's measured signal frequency and wireless signal strength emitted from the toy or object.
[0007] It is a further object to giving one or more toys/objects lifelike characteristics by studying the signal strength of an embedded wireless emitting chip in each toy or object. The signal emitted by the toy or object can be read by a mobile device/tablet/music device/wearable device with wireless signal reading and writing capabilities.
[0008] It is another object to bring life and “intelligence” to two or more toys/objects by creating a dialogue or conversation through a coordination done by a smart device according to this invention.
[0009] Furthermore, this invention should be able to give life-like characteristics to multiple toys and objects by making them communicate with one another by triggering sounds and or body movements based on remote coordination done by a smart device. The toys/objects would be separately communicating with the smart device through wireless signaling.
[0010] These objects and advantages may be accomplished with a system and method for making one or more toy more user interactive. The system comprises a Bluetooth® chip or a similar low energy signal emitting chip for each toy, a portable computing device such as a smart phone, tablet or laptop and software that sends a plurality of different commands to each toy depending on two or more of: a chronological event; relative strength of the signal received and frequency of occurrences the first toy has received one or more signals in a given time period.
SUMMARY OF THE DRAWINGS
[0011] Further features, objectives and advantages of the present invention will be made clearer with the following detailed description made with reference to the accompanying drawings in which:
[0012] FIG. 1 is a chart depicting the relative distance and signal strength from a single toy or object to a receiver/reader, like a smart phone/tablet or wearable device;
[0013] FIG. 2 is a chart depicting how different reactions in a single toy or object would be triggered by signal strength according to this invention;
[0014] FIG. 3 is a table depicting how a toy or object may produce different reactions (not listed) when correlated with time of day and signal strength according to this invention;
[0015] FIG. 4 is a table depicting how a toy or object may produce different reactions depending on the frequency of crossing paths with a receiver in a day and the signal strengths of such intercepts;
[0016] FIG. 5 is a graphic depiction of the different types of potential sensors to be integrated into a toy or object for triggering a life-like behavior therein according to one embodiment of this invention;
[0017] FIG. 6 is a chart depicting the relative distance and signal strength from multiple toys (in this case 3 ) to a receiver/reader such as a smart phone/tablet or wearable device;
[0018] FIG. 7 is a chart depicting how, according to one embodiment of this invention, a cell phone/reader may be used to coordinate interactions between a toy cat and dog;
[0019] FIG. 8 is a chart depicting how different reactions in three different toys would be triggered by relative signal strength according to this invention;
[0020] FIG. 9 is a chart depicting how three different toys could be triggered to solicit an interactive “conversation” according to this invention; and
[0021] FIG. 10 is a graphic depiction of different types of potential interactions between a plurality of toys triggered by a reader according to one embodiment of this invention.
DESCRIPTION OF PREFERRED EMBODIMENTS
For One Toy
[0022] The invention consists of creating software that reads a signal strength coming from a toy or object on a mobile device or tablet or music device or a wearable device that has the capability to read emitted signals from other devices (hereinafter, such a device is called a “READER”). The signal strength read from the emitting source would be used to create an approximation of how far the toy/object is from the READER in order to trigger in that toy/object a behavior that gives it a life-like quality. See accompanying FIG. 1 for relative signal distances.
[0023] The life-like quality of the toy/object could be expressed in the form of: an emitted sound, a conversation phrase or word, light or body movement if the device has the capability of making a sound or play conversations, or has a light or a mechanism to induce movement.
[0024] The behavior expressed by the toy/object would depend on one or more of a series of criteria. The first such criteria is: how far the toy/object is from the READER, per accompanying FIG. 2 . A different reaction will result (or otherwise be expressed in the toy/object) based on distance from the READER.
[0025] A second criterion to be considered in building life-like behavior is chronological, namely, the time of the day and day of the week. The software on the READER will read the time of the day and pair it with the signal strength between the READER and the toy/object to create a new set of reactions therefrom. The Table at accompanying FIG. 3 lists 24 potentially different toy/object reactions correlated by relative signal strength between READER and the toy/object, and by the relative time of day. Yet another variation may be combined therewith based on day of the week and/or calendar features for bringing in respective “holiday” interactions (including birthdays).
[0026] A third criterion in building life-like behavior is based on the frequency of times that the READER and Toy or Object cross path paired with the wireless strength signal when they cross paths. The Table at FIG. 4 adds this variable to the overall “mix” by factoring in the frequency of READER to toy/object interactions (or crossings of paths) in a given time period (such as one day) with relative signal strengths for causing different reaction sets (shown as AB for a Weak Signal/CD for a Medium Signal and EF for a Strong Signal). Accompanying FIG. 5 shows an example of different reactions based on certain times of the day in correlation to signal strength.
[0027] The life-like behavior on the toy/object can be triggered when it and the READER cross paths by entering into each ones area of wireless signal coverage or when the already crossed paths between the READER and toy/object leave their respective areas of wireless signal coverage.
[0028] The chip broadcasting the wireless signal on the toy/object could be built in into the toy/object OR it could also be added after the toy/object is purchased. A potential after-initial purchase wireless signal emitter unit could be stuck or attached to the outside (i.e., outer body) of that toy/object. Or, such a signal emitter can be made for embedding inside the toy/object.
[0029] In addition to a chip broadcasting the wireless signal, other life-like behaviors can be created by integrating more sensors on or into the toy/object. A representative list of sensors could include but not limited to accelerometers, temperature, light, proximity, sound, motion, pedometer, GPS, magnetometer, altimeter, etc. See, accompanying FIG. 5 .
[0030] The different sensors would be paired with the signal strength, time of the day or week, frequency of encounter to create a whole set of new interactions. Interactions can come in many different formats, examples of interactions can include but are not limited to movement, sounds, conversations or phrases, lights, vibrations etc.
[0031] All data included in an emitted wireless signal from the toy/object will be processed by the READER. That READER would then send back a signal based on the intelligence and logic built into the software to trigger the life-like behavior on the toy/object.
[0032] The toy/object might also have its own built in intelligence software and the READER software in such a scenario would interact with the intelligent software on the toy/object to create a life-like behavior.
For Two or More Toys
[0033] The invention consists of creating software that reads a wireless signal coming out of a series of toys or objects (hereafter a “TOY”) on a mobile device or tablet or music device or a wearable device that has the capability to read emitted signals from other devices (a “READER”). The signal read from the emitting TOY source would be used by the READER to coordinate a conversation with another TOY that is emitting its own wireless signal. The READER would recognize the presence of two or more TOYs and it will coordinate the trigger of sounds, voice text, music, or event movements to simulate a conversation or interaction between the two or more TOYs. The READER would take into account a series of factors into consideration to coordinate conversations including but not limited to: the number of TOYs that are in close proximity, the length of time the TOYs are within proximity of each other, the frequency of conversations that the TOYs have had in the past day/week/month/year, the type of TOY, the distance the TOYs are from one another.
[0034] Based on the wireless signals emitted from the different TOYs, the READER would trigger sounds, lights, movements that are built into the TOYs to simulate conversations, interactions, expressions of awareness.
[0035] The READER would trigger conversations or interactions in a synchronized way so as to simulate a real world conversation among the TOYs. The coordination from the READER usually leads to one TOY talking or playing sounds with or without movements while the other TOYs listening and then one of the listening TOYs would respond back by talking, playing sounds or making a physical movement or a combination of sound and movement. The back and forth exchange of sounds, music, lights and/or movements would create the perception that the TOYs are aware of one another and they are having a conversation among one another. The proposed approach to creating the perception of communication between TOYs through coordination from a smart device would reduce the cost of building TOYs that are able to communicate with one another and will also open up the opportunity to creating much richer and realistic interactions among TOYs. Also the wireless approach to coordination would ensure that the TOYs are able to have awareness and pretend to have conversations even when they are not within line of sight of one another.
[0036] The chip-broadcasting the wireless signal on the TOY could be built in into the TOY or it could also be added after the TOY is purchased. The added wireless signal emitter unit could be stuck or attached to the outside or outer body of the TOY or it could be embedded inside the TOY.
[0037] In addition to the chip-broadcasting the wireless signal, additional life-like behavior can be created by integrating more sensors in/on the TOY. A list of sensors could include but not limited to accelerometers, temperature, light, proximity, sound, motion, pedometer, GPS, magnetometer, altimeter, etc.
[0038] The different sensors would be paired with the signal strength, time of the day or week, frequency of encounter among different nearby TOYs to create a whole set of new interactions. Interactions can come in many different formats, examples of interactions can include but are not limited to movement, sounds, conversations or phrases, lights, vibrations etc.
[0039] All data included in the emitted wireless signal from the TOY will be processed by the READER. The READER would then send back a signal based on the intelligence and logic built into the software to trigger the life-like behavior on the TOY. The TOY might also have their own built in intelligence software and the READER software in such a scenario would interact with the intelligent software on the TOY to create a life-like behavior.
[0040] Additional data can be supplied to one or both toys depending on data received by one or more sensors included with one or both toys. Such sensors include, but are not limited to: an accelerometer, a temperature sensor, a light sensor, a sound sensor, a motion sensor, a pedometer, a GPS unit, a magnetometer and an altimeter
Examples of the Invention
[0041] Example #1:
[0042] An example of the invention would be to bring life to a plush dog that a kid already owns. The invention involves adding a tag to the neck of the plush dog. The tag includes an accelerometer, a speaker and a Bluetooth® wireless chip.
[0043] To bring the plush dog to life, the Child will download a software on his/her smartphone and activate the Bluetooth® feature on his/her phone. The Child will pair the Bluetooth® device on the plush dog with his/her smartphone's Bluetooth®. Bluetooth® has a range between 50 and 150 feet. Once the Child's Smartphone reads the broadcast from the plush dog Bluetooth® unit (when the phone and the plush dog come into close proximity within less than the 50-150 feet range), the software on the phone will send a signal to the plush dog tag and based on the logic in the software, the tag starts making a barking sound.
[0044] If the Child happens to get very close to the dog (distance <3 feet), the signal strength read by the phone would be very high and the Dog tag in this case will make a sniffing sound based on the Bluetooth® signal sent back from the child's smartphone.
[0045] If the Child disappears from the Bluetooth® signal range and then shows up in the Bluetooth® signal range later in the evening, the Dog tag starts to make a sleepy sound. If the child happens to pick up the plush dog and rock it (triggering the accelerometer on the dog), the plush dog will fall asleep and the tag starts to make snoring sound.
[0046] If the plush dog is sleeping, once the child's smartphone gets closer to the dog, the dog will make a sleeping sound. The “sleeping” sound trigger will be activated by a signal sent from the software on the smartphone to the tag via Bluetooth®.
[0047] Example #2:
[0048] A truck that has a built in Bluetooth® chip, a speaker, an accelerometer and a set of lights. The Kid will download a gaming software application on their smartphone that connects through the phone's Bluetooth® to the truck's Bluetooth® chip. The Kid will program the truck to make an engine starting sound as his smartphone gets close to the truck to signal that it is ready to play with the kid. The truck's engine will turn off as the Kid moves away from the truck's Bluetooth® coverage signal area.
[0049] The truck will also trigger a horn sound if the Kid's smartphone gets too close to it. The truck can also make different sounds and turn on its lights at night to signal to the Kid that it wants to play as the Kid's smartphone get in close proximity with the truck's Bluetooth® area of coverage.
[0050] Example #3:
[0051] An elderly individual wears a small bracelet that has Bluetooth® wireless sensor on it. The bracelet is intended to interact with a robotic creature that would communicate with the elderly individual and encourage him or her to take their medicine and weigh themselves on a smart scale on a daily basis.
[0052] As the elderly individual walks into Bluetooth® wireless signal range for the robot, depending on the time of the day, the robot will talk to the elderly individual and remind him\her to take their medicine and weight themselves. Once the elderly individual walks away from the Bluetooth® wireless signal range of the robot, the robot will talk to and encourage that elderly individual to come back for a chat later in the day.
[0053] The wireless signal strength analysis software coupled with the time of the day will help create a companion for the elderly and encourage them to take care of their own health.
[0054] Example #4:
[0055] An example of the invention would be to add value and liveliness to a Toy pet such as a plush dog. The toy dog in this case would have a built in Bluetooth® chip that can trigger a sound that is saved on a chip inside the dog. A smart device such as an Apple iPhone® can communicate with the dog through Bluetooth® signaling. Through a software application on the iPhone®, the iPhone® can connect to the dog and trigger sounds that are saved on the dog. The software application will also be able to connect to nearby similar toy pets made by the same manufacturer. The application on the iPhone® will connect to one of the dogs and trigger a sound such as a bark and after about a second the application will connect to the second dog and will trigger another sound bark in a way that seems that the two dogs are aware of one another and they are communicating with one another as real dogs would.
[0056] If two toy dogs happen to be in the same environment for the first time, one dog might growl at the other dog and the second dog will also respond with a growling sound too. The same two dogs might interact in a more friendly way, if they happen to have seen one another in the past. | A system and method for making one or more toy more user interactive. The system comprises a low energy signal emitting chip such as a Bluetooth® for each toy, a portable computing device such as a smart phone, tablet or laptop and software that sends a plurality of different commands to each toy depending on two or more of: a chronological event; relative strength of the signal received and frequency of occurrences the first toy has received one or more signals in a given time period. | 0 |
BACKGROUND OF THE INVENTION
This invention relates to a holding device and has been devised particularly though not necessarily solely for use in holding beverage cans which are necked at one end.
It is often convenient to assemble a group of articles such as beverage cans into a batch or group for ready transportation or storage. One method of achieving this is to put the articles into a box or tray or provide a full wrap about the articles. Such methods are wasteful of packaging material.
Attempts to reduce the amount of required packaging material have been made. For example, U.S. Pat. Nos. 3,414,313 and 3,075,799 to Schwartz and Weiss, respectively, each show constructions which engage the top of a can. However, each construction requires a substantial width of space to fold the holder onto the cans. Also, the particular constructional method used means that the technique cannot be extended to multiple rows of cans.
U.S. Pat. No. 3,245,711 to Dantoin shows a construction which can receive multiple rows of cans but requires complex folding of the holding material to achieve its result.
U.S. Pat. No. 3,653,503 to Federal Paper Board Company describes a construction wherein the tops of cans are held by a sheet material pushed downwardly between two rows of cans and at the edges of the sheet. The package is held in this position by a cover formed by end panels which are folded over the top of the cans and parts of the holding device engaged to the cans. The construction is however disadvantageous in that substantially space is required on each side and above the assembly line to accommodate the movements required of the end panels.
Furthermore, the large area of packaging material introduces complexities into handling.
Plastics packaging is available in the form of interconnected rings of plastics material having some stretch. While such packaging has found wide acceptance it too is disadvantageous in view of the long period required for discarded packaging to degrade plus the possibility of wild life being often fatally trapped or choked by the rings of material.
BRIEF SUMMARY OF THE INVENTION
It is therefore an object of the present invention to provide a holding device and/or a method of holding articles which will obviate or minimize the foregoing disadvantages in a simple yet effective manner.
Accordingly in one aspect the invention consists in a holding device comprising a sheet member shaped and configured to form a channel therein, means to receive the rims of a plurality of articles each having a rim, and a separate bridge part able to be connected to the sheet member so as to span the channel to maintain the channel in the sheet and thereby maintain the articles in engagement with the sheet in use.
In a further aspect the invention consists in a holding device comprising a sheet member shaped and configured to form a channel therein, means to receive the rims of a plurality of articles each having a rim, and a separate bridge part spanning the channel and connected to the sheet member at each side of the channel to maintain the channel in the sheet and thereby maintain the articles in engagement with the sheet in use.
In a still further aspect the invention consists in a method of holding articles comprising the steps of providing a sheet member forming a channel in the sheet member and engaging the sheet member with the rim of a plurality of articles, each having a rim, and engaging a bridge part across the channel to maintain the channel in the sheet and thereby maintain the articles in engagement with the sheet.
This invention may also be said broadly to consist in the parts, elements and features referred to or indicated in the specification of the application, individually or collectively, and any or all combinations of any two or more of the parts, elements or features, and where specific integers are mentioned herein which have known equivalents in the art to which this invention relates, such known equivalents are deemed to be incorporated herein as if individually set forth.
The invention consists in the foregoing and also envisages constructions of which the following gives examples.
BRIEF DESCRIPTION OF THE DRAWINGS
One preferred form of the invention will now be described with reference to the accompanying drawings wherein:
FIG. 1 is a plan view of one form of sheet member able to be used in a holding device according to the invention;
FIG. 2 is a plan view of an alternative sheet member;
FIG. 3 is a plan view of one form of bridge member able to be used in conjunction with the sheet member of FIG. 1 or FIG. 2 to form a holding device according to one preferred form of the invention;
FIG. 4 is a plan view of an alternative bridge member for use with larger numbers of articles to be held;
FIG. 5 is a perspective view of a holding device according to the invention, in use and showing an alternative bridge member;
FIG. 6 is an exploded perspective view of a holding device according to the invention;
FIG. 7 is a perspective view of the holding device of FIG. 6 in assembled form;
FIG. 8 is an end view of the construction of FIG. 5;
FIG. 9 is a perspective view of a holding device according to the invention in a further alternative form;
FIG. 10 is a perspective view of a holding device according to the invention in a still further alternative form in which a larger number of articles are held by the holding device;
FIG. 11 is a perspective view of an alternative form of the invention shown in FIG. 10;
FIG. 12 is an end view of the construction of FIG. 10, and
FIG. 13 is a plan view of a sheet forming part of an alternative construction to that shown in FIGS. 10 to 12.
DETAILED DESCRIPTION
Referring to the drawings, a holding device is provided which comprises a sheet member 1 formed of a sheet material such as, for example, paper board or cardboard and the sheet member 1 is shaped and configured so that a channel can be formed therein and so that the sheet member can engage the rims of a plurality of rimmed articles, such as cans. The cans may be beverage cans in which the operable end is necked but the invention may be used with other rimmed cans or rimmed articles. This may be achieved by providing the sheet 1 with at least three substantially parallel fold lines 2, 3 and 4.
If the fold lines 3 and 4 are folded so that the fold line 2 is out of the plane of the sheet member 1 a channel 5 will be formed as can be clearly seen in FIGS. 6 and 8.
The sheet member 1 described herein is designed to be engageable with a necked article, for example, a beverage can 6 of the type which is provided with a neck at the top end terminating in a rim. The rim is able to be engaged with pairs of substantially arcuate slots such as 7a and 7b, that is to say slots which are substantially arcuate, though as can be seen from FIGS. 1 and 2 the preferred slot is not arcuate being somewhat flattened. The precise shape of the slots 7a and 7b will depend on the radius of the can top and size of the can rim. Thus, the best shape of slots 7a and 7b can be determined empirically for any particular article to be held.
The slots 7a and 7b are provided in pairs and in FIG. 1 and 2 two rows of three pairs of slots are provided so that the holding device including the sheet 1 will hold six beverage cans. It will be immediately apparent that other numbers of pairs of slots could be provided to hold different numbers of cans, for example, two rows of four cans to form eight cans or three rows of four cans to form twelve cans by way of example. Where twelve cans in three rows of four are to be provided then two substantially parallel channels 5 would be provided. A twelve can construction will be described further herein.
The outer side edges 8 of the sheet member 1 are also separated from the remainder of the material by fold lines 9 and 10 so that the outer parts 8 can be folded to at least some extend downwardly to engage the can rims 11. Fold lines 9 and 10 are substantially parallel to fold lines 2, 3 and 4.
The sheet material 1 is desirably modified about slots 7a and 7b so as to increase the engagement between the sheet material 1 and the can rims 11. In FIG. 1 this is achieved by providing sunburst type slots or slits 13 and in FIG. 2 this is achieved for example by providing outwardly converging crease lines as at 14.
Where the article to be held is a typical soft drink or beer can the crease lines 14 in a pair may be about 1.2 cm apart at the edge 15 of the sheet 1 and about 1.7 cm apart at the slot 7a where the shortest distance from the edge 15 to slot 7a is about 1 cm. Again, radius and rim size may affect these dimensions and the best angles and length can be empirically determined for any selected can. The crease lines 14 are shown extending substantially from edge 15 to slot 7a but can and rim size again may require that the crease lines 14 are shorter than this.
A bridge piece 20 is provided to span the channel 5 as can be seen, for example, in FIG. 7. Thus, in use the cans 6 are held in the desired arrangement and the sheet member 1 placed thereover so that the rims 11 catch in the arcuate slots 7a and 7b. This can be arranged to be done mechanically by providing suitable pressure members in the desired positions. As the channel 5 is formed the two rows of cans 6 are moved relatively inwardly.
The bridge piece 20 is then placed across the channel 5 being, for example, glued or adhered into position. The bridge piece 20 is glued or adhered to the arms 21 at each side of the channel 5.
The bridge member 20 preferably includes a handle and for example in FIG. 3 a pair of cut outs 22 may be provided with a tongue 23 extending into the cut out 22. The dimensions of the tongue 23 are such that the tongue 23 may be pressed into the channel 5 in the erected holding device, preferably being a close fit. A crease or fold line 24 may be provided to facilitate movement of tongue 23 into the channel 5 in use.
In the embodiment of FIGS. 5 and 8 the bridge piece 20 has down turned side edges 30 separated from the body of bridge piece 20 by fold lines 31. The down turned side edges 30 give some protection to the exposed can rims 11 and can be adhered to the edge of down turned parts 8 of the sheet 1 if desired or necessary.
In FIG. 9 the bridge piece 20 has an upwardly extending portion 40 with cut out 41 therein so as to provide a more conventional handle. The double thickness upwardly extending portion 40 may have the two sheets adhered one to the other and crease lines 42 may be formed between the portion 40 and the remainder of the handle.
In the embodiment of FIG. 10 twelve cans 6 are held by a pair of sheet members 1A or 1B. They are spanned by the bridge piece 20 shown in FIG. 4. The tongues 23 are pushed in use into a third channel 50 formed by adjacent side edges 8 of the two sheet members 1A or 1B. The bridge piece 20 is adhered to each of the four areas 21 in the preferred construction.
The construction of FIG. 11 is as for FIG. 10 save that the bridge part 20 has side edges 60 similar to those described for FIG. 5.
FIG. 13 shows an alternative sheet 1 for holding twelve cans. The sheet 1 has fold lines 2, 3 and 4 represented so that in the erected construction two channels 5 are formed. These may be mounted by adhering a bridge part 20 as shown, for example, in FIG. 4 to the construction. The bridge part 20 is adhered preferably to the edge of the three areas 21 and is therefore oriented in a direction at right angles to the direction of orientation of the bridge part 20 shown in FIGS. 10 to 12.
In use the holding device is applied to necked beverage cans in particular in the manner described. The cans may then be carried as desired and simply removed by a levering or twisting type action between the beverage can or other article and the holding device. The material from which the sheet material is made must be of sufficient stiffness to retain the cans in position but of sufficient flexibility so that the cans can be removed therefrom when desired.
Thus it can be seen that at least in the preferred form of the invention a holding device is provided and/or a method of holding articles is provided which has the advantage that the holding device can be made of cardboard or paperboard which has environmental advantages and which uses substantially less material than full wrap around or other single piece constructions. That is to say the volume of packaging material used is minimized. One large area of board is more difficult to handle than the two smaller areas of the invention. This is particularly so when the packaging is operating at commercial speeds.
The two piece construction of the invention has other advantages. For example, the manufacturer can cross grain the two pieces of board which has its maximum tear strength across the grain. Thus, the sheet member can have its grain running one way and the bridge have its grain running the other. Thus, lighter weight board can be used than in a one piece construction while retaining adequate strength. Also, the two piece construction gives flexibility in printing as combinations can be made. A user could, by way of example, print the sheet member on a "house" basis and the bridge on a "brand" basis allowing the thus more generic sheet member to be associated with a selected bridge of those available.
The construction is such that the loading operation of articles into holding devices can be effected in a way that is economical of machine space, particularly where multiple lines are operating and also economical in board usage. The construction is also advantageous in allowing the use of paper board or cardboard which being more biodegradable than plastics is less likely to cause environmental damage than packaging formed from many of the available plastics materials. | A holding device including a sheet member (1) shaped and configured to form a channel (5) therein, slots (7a, 7b) in the sheet member to receive the rims (11) of a plurality of articles each having a rim, and a separate bridge part (20) connected to the sheet member (1) so as to span the channel (5) to maintain the channel (5) in the sheet member (1) and thereby maintain the articles in engagement with the sheet member (1) in use. | 1 |
CROSS REFERENCE TO A RELATED APPLICATION (S)
This application is a National Phase Patents Applications and claims priority to and benefit of International Application Number PCT/CN2010/080549, filed on Dec. 30,2010, which claims priority to and benefit of Chinese Patent Application Number 201010222446.0, filed on Jul. 9,2010, the entire disclosure of which are incorporated herein by reference.
TECHNICAL FIELD
The present invention relates to a microsphere containing an anti-tuberculosis drug and a vascular targeted embolic agent comprising the microsphere, particularly relates to a sustained-release microsphere with moxifloxacin as an anti-tuberculosis active ingredient and sodium alginate as a carrier for crosslinking and vascular targeted embolic agent thereof. The present invention also relates to a method for preparing the sustained-release microsphere, and use of the microsphere in preparing drugs for treating pulmonary tuberculosis, mass hemoptysis of pulmonary tuberculosis, pulmonary tuberculosis cavity, renal tuberculosis, thyroid tuberculosis, cervical lymph node tuberculosis, genital tuberculosis (fallopian tube tuberculosis, endometrium tuberculosis, testis tuberculosis, epididymis tuberculosis), pericardial tuberculosis, chest wall tuberculosis, pleural tuberculosis and other tuberculosises in the body through interventional embolization.
BACKGROUND TECHNOLOGIES
Tuberculosis is one of major infectious diseases seriously harming human life and health, and also becomes the number-one killer in infectious diseases and the leading cause of death for adults. In the late 1990s, due to drug-resistant bacteria and other issues, the tuberculosis which had disappeared made a comeback throughout the world, which increased difficulties in controlling the tuberculosis. The World Health Organization has made preliminary statistics showing that 1.9 billion people around the world are infected by tuberculosis bacilli, the number of patients with tuberculosis has been up to about 20 million, the number of new cases is up to 8 million each year, and 3 million people on average die from tuberculosis each year. In China, the number of patients infected by tuberculosis bacilli are also rising, and tuberculosis presents an upward trend, the number of patients with tuberculosis ranks the second in the world, and the number of deaths due to tuberculosis each year is about 150,000; prevention and treatment of tuberculosis is a major issue that needs to be resolved urgently, and therefore research and development of new anti-tuberculosis drugs and new dosage forms is imminent.
Mycobacterium tuberculosis mainly parasitizes in normal cells and has some resistance to drugs, and Mycobacterium tuberculosis can be killed only when concentration of an anti-tuberculosis drug in the cell reaches a certain level. Oral formulations of anti-tuberculosis drugs are often influenced by the first-pass effect firstly, and subjected to protein binding, metabolism, excretion, decomposition and other processes during circulating around the body, but only a small amount of drug can reach the target tissue, target organ and target cell, therefore, in order to improve concentration of the drug in the target area, dose of the drug must be increased, which enhances systemic toxic and side effects of the drug. Targeted formulations have characteristics such as directionally releasing drugs, increasing concentration of drugs in lesion sites and cells, improving efficacy, reducing toxic and side effects, therefore it is considered that the anti-tuberculosis drug targeted formulations have clinical application value and development prospects.
Moxifloxacin, which belongs to the fourth-generation chemically synthesized antibiotic drugs of fluoroquinolones, is a product launched by Bayer (Germany) in 1999. Moxifloxacin blocks replication of DNA by inhibiting activities of bacterial DNA gyrase A subunit and topoisomerase IV to play roles in killing bacteria. For gram-negative bacteria, moxifloxacin mainly inhibits the DNA gyrase, and for gram-positive bacteria, the primary action target is the topoisomerase IV. Chemical structure of moxifloxacin is characterized in that the methoxyl is introduced to the 8 th carbon atom, which increases the drug's capability of binding to the bacteria and capability of penetrating and destroying the cell membrane, and its post-antibiotic effect (PAE) is strong and lasting.
Moxifloxacin retains antibacterial activity and antibacterial spectrum of quinolone drugs on gram-negative bacteria, and the methoxyl at the 8 th carbon atom increases antibacterial activity and broadens antibacterial spectrum of moxifloxacin on gram-positive bacteria. Moxifloxacin is extremely effective to atypical pathogens such as mycoplasma pneumoniae, chlamydia, and legionella, and has strong activity on anaerobic bacteria, for example, it has significant antibacterial activity on anaerobic bacteria with or without spores. Moxifloxacin is also effective to bacteria which are resistant to antibiotics of β-lactams, macrolides, amino glycopeptides and tetracyclines. Moxifloxacin, different from the hepatic cytochrome P-450 isozyme inhibitor, has no drug cross-resistance with these antibiotic drugs, thus avoiding many potential interactions between drugs. Moxifloxacin has similar early bactericidal activity to isoniazid (INH) or rifampin, and has bactericidal activity for early and extended early stage of patients with pulmonary tuberculosis, which shows that moxifloxacin can well penetrate into the tuberculosis lesion sites and quickly kill the fast growing flora in the sputum of patients with severe cavitary pulmonary tuberculosis.
Since it is on the market, moxifloxacin has been widely applied clinically due to its advantages such as broad antibacterial spectrum, strong antibacterial power, wide distribution in the body, high drug concentration in the body, long half-life, good efficacy, little side effects, no drug cross-resistance with other antibacterial drugs, almost no photosensitive reactions and the like. With wide application of anti-tuberculosis drugs clinically, drug resistance of Mycobacterium tuberculosis gets higher and higher, especially the problem of multi-drug resistance, which has become a subject of concern for the anti-tuberculosis field, and is also a main factor impacting chemotherapy effect on tuberculosis. Therefore, selecting an appropriate dosage form of an anti-tuberculosis drug is important for the current treatment and control of tuberculosis.
Phenomenon of recurrence of tuberculosis and drug resistance of tuberculosis bacilli is becoming more and more serious, despite that there are complex causes for the occurrence of the phenomenon, a very important factor is long treatment course, making patients be unable to take medicine with full amount regularly till the end of treatment, which is a common problem faced in the treatment of tuberculosis in countries of the world. On the premise of ensuing therapeutic effect, the problem of drug compliance can be effectively resolved by reducing dose of a drug and prolonging intervals of administration. In order to obtain an anti-tuberculosis drug formulation which can play a long-lasting effect in human body, we have selected a natural polymer, sodium alginate, with good biocompatibility as a carrier and moxifloxacin as a model drug, to crosslink with an adsorbent, so as to obtain a vascular embolic agent containing sustained-release biodegradable microspheres by prescription selection, release experiments in vitro and studies in vivo.
There are only sporadic reports about study on microspheres carrying an anti-tuberculosis drug at home, most of drugs reported are drugs to be administered orally or by injection. At abroad, systematic study reports about microspheres carrying an anti-tuberculosis drug are mainly concentrated in study groups of America, Japan and India, involving different carriers, different drugs, different microsphere size and different routes of administration. Some scholars were dedicated to study on the anti-tuberculosis sustained-release system before, mainly involving oral agents, inhalants, injections, and subdermal implants.
Currently, clinical anti-tuberculosis drugs are mainly oral and injectable formulations, and the efficacy of the injectable formulation is not ideal. Application of anti-tuberculosis drugs is greatly limited since effective drug concentration cannot be obtained at the lesion site and significant systemic toxicity and drug resistance occur in the application process. A few therapies of embolism plus drug infusion have the following defects: the drug cannot be sustainedly released in a relatively uniform form, and the “shock wave” efficacy of the drug may cause necrosis or damage to local tissues when local drug infusion concentration is too high.
Anti-tuberculosis drug microsphere vascular embolic agent is a new dosage form, wherein microspheres deposit in the lung, which can delay release of the drug, protect the drug from being destroyed by enzyme hydrolysis, and prolong retention time of the drug in the lung, and also has advantages in low incidence rate of side effects, good toleration and safety. At present, there has been no reports at home and abroad about an anti-tuberculosis vascular embolic agent prepared by crosslinking moxifloxacin with sodium alginate and an adsorbent, and about application of the anti-tuberculosis vascular embolic agent in treating patients with pulmonary tuberculosis, mass hemoptysis of pulmonary tuberculosis, pulmonary tuberculosis cavity, bronchial stenosis of pulmonary tuberculosis, multi-drug resistant cavitary pulmonary tuberculosis, renal tuberculosis, thyroid tuberculosis, genital tuberculosis (fallopian tube tuberculosis, endometrium tuberculosis, testis tuberculosis, epididymis tuberculosis), cervical lymph node tuberculosis, pericardial tuberculosis, chest wall tuberculosis, and other tuberculosises of other parts in the whole body through interventional embolization.
Moxifloxacin belongs to the fourth-generation chemical antibiotic drugs of fluoroquinolones, with poor solubility in water and organic solvents. Oral and injectable formulations of moxifloxacin are usually applied clinically and have defects as follows: amount of oral absorption is small, dose of injection is low, an effective drug concentration cannot be obtained at the lesion site, releasing cannot be performed in a relatively uniform and sustained form, and adverse reactions are easily caused.
SUMMARY OF THE INVENTION
The present invention provides a sodium alginate crosslinked moxifloxacin sustained-release microsphere, wherein the microsphere comprises: a drug carrier, adsorbent, anti-tuberculosis drug active ingredient, strengthening agent and curing agent, the carrier is sodium alginate, the adsorbent is human serum albumin or bovine serum albumin, the anti-tuberculosis drug active ingredient is moxifloxacin, the strengthening agent is gelatin or hyaluronic acid, and the curing agent is a salt of divalent metal cation such as divalent calcium or barium salt.
In one embodiment, the sustained-release microsphere is preserved in a vegetable oil or liquid paraffin as a preservation solution, and the particle size of the microsphere is in the range of 50˜100 μm, 50˜150 μm, 50˜200 μm, 100˜300 μm, 150˜450 μm, 300˜500 μm, 500˜700 μm, 700˜900 μm or 900˜1,250 μm.
In another embodiment, the microspheres are made into dry powdered particles with particle size in the range of 10˜50 μm, 25˜50 μm, 50˜100 μm, 100˜350 μm, 300˜550 μm or 500˜750 μm.
In the sustained-release microsphere of the present invention, the weight ratio of sodium alginate and moxifloxacin is preferably 1˜75:0.25˜12.5.
The present invention also provides a method for preparing the above-mentioned sustained-release microsphere, which comprises the following steps:
1) dissolving sodium alginate with physiological saline or water for injection based on mass-volume percentage of 0.5-15% to obtained a sodium alginate solution, i.e., a carrier solution; 2) dissolving human serum albumin or bovine serum albumin with water for injection based on mass-volume percentage of 0.1-10% to obtain a albumin solution, i.e., an adsorbent; 3) grinding, stirring, dissolving and adsorbing moxifloxacin with the adsorbent prepared in step 2) to obtain a moxifloxacin solution, i.e., a drug solution, wherein moxifloxacin and the adsorbent are added in an amount of mass-volume percentage of 1.6-4%; 4) preparing an aqueous solution of 1-15% by mass-volume with a salt of divalent metal cation such as divalent calcium or barium salt to obtain a curing solution; wherein the calcium salt is preferably selected from calcium chloride and calcium lactate, the barium salt is preferably barium chloride; 5) adding anhydrous ethanol and water for injection into the resulting curing solution, wherein the volume ratio of the resulting curing solution, anhydrous ethanol and water for injection is 2:1:2, so that a curing solution containing anhydrous ethanol is obtained; 6) dissolving gelatin or hyaluronic acid with water for injection to obtain a gelatin or hyaluronic acid solution of 0.1-10% by mass-volume, i.e., a strengthening solution; 7) pooling the drug solution and the carrier solution at a volume ratio of 1:1˜30, and magnetically stirring the solution uniformly to obtain a preparing solution; 8) spraying the above-obtained preparing solution by a high voltage electrostatic multi-head microsphere generating device to obtain droplets which are then dispersed in the curing solution, and removing supernatant when precipitation is completed , to obtain sodium alginate crosslinked microspheres or micro-gel beads containing moxifloxacin; 9) adding the above-obtained microspheres or micro-gel beads into the strengthening solution, stirring the solution, and discarding supernatant to obtain microspheres or micro-gel beads containing drug, i.e., sodium alginate crosslinked moxifloxacin sustained-release microspheres.
In one embodiment, the sodium alginate crosslinked moxifloxacin sustained-release microspheres containing drug obtained in step 9) are preserved in vegetable oil or liquid paraffin oil as a preservation solution. The vegetable oil may be selected from soybean oil, tea oil, corn oil, rapeseed oil, cottonseed oil or other oils for injection.
Or, in another embodiment, the sodium alginate crosslinked moxifloxacin sustained-release microspheres are dried to obtain powered particles, i.e., dry spheres, for example, the method of freeze drying or oven drying is employed.
In one special embodiment, the high voltage electrostatic multi-head microsphere generating device used in step 8) comprises: a high voltage electrostatic generating device, propulsion pump, ejecting head, sterile container, a plurality of positive and negative electrodes, sterile syringes of various models, and lifting device, wherein the high voltage electrostatic generating device is provided with the plurality of positive and negative electrodes, the propulsion pump is connected to the sterile syringe and the ejecting head, the positive electrode is connected to the ejecting head, the negative electrode is connected to a stainless steel wire immersed in the curing solution, the stainless steel wire is connected to the sterile container, and the lifting device for adjusting distance is under the stainless steel wire and the sterile container.
When preparing microspheres with the preparing solution, a high electric field is generated between the positive and negative electrodes of every group after the high voltage electrostatic multi-head microsphere generating device is powered on, when the propulsion pump pushes out the mixed solution of sodium alginate and the adsorbed drug at a constant speed, the electric field force overcomes the inherent viscous force and surface tension of the sodium alginate solution and makes the drug-containing polymer solution disperse into droplets of a certain size which are ejected to the curing solution and crosslinked quickly into calcium alginate microspheres (micro-gel beads). In order to prevent the water-soluble drug from releasing too early, the micro-gel bead is coated with the gelatin solution in the present invention; and in order to prevent the releasing (leaking) of the water-soluble drug from microspheres during the preservation period, the present invention employs a vegetable oil (or liquid paraffin) for preservation, which forming a water-in-oil system, so that loss of the drug before application can be avoided; the present invention employs the technology of high voltage electrostatic preparing sphere (capsule) so that organic solvents can be avoided, which helps to improve stability of the drug, and the particle size of the microsphere (capsule) can be adjusted by adjustment of voltage, the operation is simple and convenient, and the operation condition is mild, the toxic organic solvents and glutaraldehyde used in the prior art can be avoided, and the product of the present invention is environmentally friendly.
The present invention prepares microspheres in the presence of the divalent metal cation (calcium or barium ion) by using sodium alginate as a drug carrier crosslinking agent, the anti-tuberculosis drug of moxifloxacin as a drug active ingredient, and albumin as an adsorbent to link moxifloxacin and sodium alginate, and then the microspheres are coated with gelatin, which resolves the problem of too fast releasing of the water-soluble drug; in terms of preservation, autoclaved vegetable oil or liquid paraffin is used to preserve the wet gel drug microspheres so that moxifloxacin is not released when it is not used. The present invention changes the dosage form and administration route of the moxifloxacin anti-tuberculosis drug so as to achieve effects of efficient, low toxicity, and achieve safe and effective clinical application.
In the present invention, the anti-tuberculosis drug of moxifloxacin and the adsorbent (human serum albumin or bovine serum albumin) are grinded and dissolved, and mixed in proportion, before combined together by adsorption, and then crosslinked by with the sodium alginate carrier; and the anti-tuberculosis drug of moxifloxacin is wrapped in the microspheres by the high voltage electrostatic multi-head microsphere generating device in the presence of the divalent metal cation (calcium or barium ion); in order to prevent the anti-tuberculosis drug of moxifloxacin from releasing to the preservation solution, the microsphere is further coated with gelatin which forms a thin membrane around the microsphere, and then put into the autoclaved vegetable oil or liquid paraffin to preserve wet gel drug microspheres, so that the sodium alginate microsphere vascular targeting embolic agent containing moxifloxacin is prepared.
The present invention further relates to a vascular targeted embolic agent containing the above-mentioned sodium alginate crosslinked moxifloxacin sustained-release microsphere.
The present invention further relates to a use of the above-mentioned sodium alginate crosslinked moxifloxacin sustained-release microsphere in preparing a vascular targeted embolic agent. Said vascular targeted embolic agent may be used for treating tuberculosis, for example, used for treating pulmonary tuberculosis, mass hemoptysis of pulmonary tuberculosis or pulmonary tuberculosis cavity through interventional embolization; used for treating renal tuberculosis, thyroid tuberculosis, cervical lymph node tuberculosis, pericardial tuberculosis, chest wall tuberculosis and/or pleural tuberculosis; and used for treating fallopian tube tuberculosis, endometrium tuberculosis, testis tuberculosis or epididymis tuberculosis.
BENEFICIAL EFFECTS
The present invention has the following advantages:
1. a high voltage electrostatic multi-head microsphere generating device produced industrially is selected, so that the drug microsphere vascular targeted embolic agent suitable for different clinical uses with controllable size can be produced; 2. a natural polymer material, with good biocompatibility, i.e. sodium alginate is select as a drug carrier, so that a vascular targeted embolic agent containing biodegradable sustained-release drug microspheres can be obtained; 3. human serum albumin or bovine serum albumin is selected as an adsorbent, so that the anti-tuberculosis drug of moxifloxacin can be absorbed well.
The formulation of the present invention can not only improve local drug concentration greatly, decrease concentration of the drug in the circulation system, reduce toxicity of the drug to normal tissues, but also facilitate application of the drug greatly, reduce courses of treatment, shorten time for treatment, and reduce drug complications, treatment costs for patient and drug tolerance. In the treatment with the formulation of the present invention, the method of interventional radiology or bronchoscopic intervention is employed to perform target organ artery angiography, then embolic microspheres are chosen after the diameter of the embolic microspheres are determined according to the findings shown in angiography, and treatment of embolizing the target organ is performed with the chosen embolic microsphere, especially embolizing the peripheral small artery blood vessel of the target organ. Treatment of embolizing the peripheral small artery blood vessel may be considered for the following patients with pulmonary tuberculosis or following conditions: (1) patients subjected to failure in initial treatment and retreatment by adoping anti-tuberculosis therapy whose smear test shows tuberculosis-positive after the course of retreatment and sputum culture shows that Mycobacterium tuberculosis is resistant to two or more HR anti-tuberculosis drugs, i.e., multiple-drug resistant; (2) patients with the following symptoms: there is a single thin-wall or caseous cavity with tuberculosis bacilli in the sputum being persistently positive, and no apparently active lesion is around the cavity or the lesion has been stable; (3) patients with single fiber cavity of pulmonary tuberculosis and no negative conversion of sputum bacillus occurring after long time of treatment; (4) bronchial tuberculosis patients with sputum bacilli being persistently positive after long time of treatment; (5) interventional embolization treatment for mass hemoptysis of pulmonary tuberculosis; (6) intervention treatment for tuberculosises other than pulmonary tuberculosis, such as, renal tuberculosis, thyroid tuberculosis, cervical lymph node tuberculosis, pericardial tuberculosis, chest wall tuberculosis, pleural tuberculosis and genital tuberculosis (fallopian tube tuberculosis, endometrium tuberculosis, testis tuberculosis, epididymis tuberculosis), or the like.
When the formulation of the present invention is used, a micro-catheter is preferably used to perform superselective embolization, the sterile operation is employed, and injection is performed slowly as required or slowly performed multiple times under fluoroscopy through the catheter until the flow rate of the contrast agent decreases significantly, and embolization is completed. Further artery angiography is performed to evaluate embolization effect. During application, if the sodium alginate microsphere vascular embolic agent containing the moxifloxacin anti-tuberculosis drug is powdered particles, dry spheres preserved in a sealed container are firstly dissolved in physiological saline to reconstituted to wet spheres, then an appropriate amount of contrast agent or diluted contrast agent is added and the mixture is mixed uniformly to make the microspheres fully suspended in the contrast agent, then under monitoring by an imaging equipment, the mixture is injected into the blood vessel at the lesion site slowly or injected slowly multiple times by catheter, so as to achieve a super-selective embolization until the flow rate of the contrast agent decreases obviously, and embolization is completed. Further artery angiography is performed and embolization effect is determined.
The outstanding advantages of the present invention are as follows: human serum albumin or bovine serum albumin used as an adsorbent are safe and effective, which successfully resolves the problem that moxifloxacin cannot dissolve in water or organic solvents completely, the difficult problem that when the combination of moxifloxacin and the albumin is mixed and crosslinked with water-soluble sodium alginate solution, the mixture is unsinkable, and the problem that drug microspheres cannot be formed when moxifloxacin reacts with other reagents and is wrapped under the action of positive and negative electric fields; size of anti-tuberculosis drug microspheres prepared is ideal and controllable, and the microsphere vascular embolic agent prepared has characteristics of high drug loading, long retention time in the body and high bioavailability, adjustable drug releasing rate, being capable of achieving targeted delivery of the drug, and target specificity, and can be used to treat pulmonary tuberculosis, mass hemoptysis of pulmonary tuberculosis, pulmonary tuberculosis cavity, renal tuberculosis, thyroid tuberculosis, cervical lymph node tuberculosis, genital tuberculosis (fallopian tube tuberculosis, endometrium tuberculosis, testis tuberculosis, epididymis tuberculosis), pericardial tuberculosis, chest wall tuberculosis, pleural tuberculosis and other tuberculosises in the body through interventional embolization.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention will be further illustrated in combination with embodiments, and it should be understood that the preferred embodiments described herein are only used to illustrate and explain the present invention, rather than limit the present invention.
Example 1
Preparation of Sodium Alginate Crosslinked Moxifloxacin Anti-Tuberculosis Microsphere Vascular Embolic Agent
1. Treatment of glassware:
The cleaned glassware was dried out in the air and then placed and baked in the high-temperature oven (for sterilization and depyrogenation) to be used.
2. Selection of Microsphere Preparing Device:
A high voltage electrostatic multi-head microsphere generating device, which can controllably prepare spheres with uniform size, is simple and convenient to operate, has high output, and easily implements mass production, was selected.
3. Method for Preparing Various Reagents: (1) Preparation of sodium alginate solution:
8 g of sodium alginate was weighed and placed in a glassware, then 500 ml of physiological saline or water for injection was added into the glassware while stirring, magnetical stirring was performed until all the sodium alginate was dissolved to obtain a sodium alginate solution;
(2) Preparation of adsorbent:
Human serum albumin (or bovine serum albumin) was dissolved with water for injection at a ratio of 0.1˜10% (mass-volume percentage) to obtain an albumin solution, i.e., an adsorbent;
(3) Preparation of moxifloxacin solution:
12 g of commercially available moxifloxacin was weighed, placed in a glassware, and dissolved with 50 ml of the human serum albumin or bovine serum albumin solution of 0.1˜10% (mass-volume percentage) by stirring to obtain a moxifloxacin solution;
(4) Preparation of gelatin strengthening solution:
30 g of gelatin was placed in a glassware, 500 ml of physiological saline or water for injection was added into the glassware while stirring, magnetical stirring was performed until all the gelatin were dissolved to obtain a gelatin strengthening solution;
(5) Preparation of curing solution containing anhydrous ethanol:
200 g of calcium chloride or barium chloride or calcium lactate was weighed and placed in a glassware, 4,000 ml of water for injection was added into the glassware while stirring, magnetical stirring was performed until the calcium compound was dissolved, and then 1,000 ml of anhydrous ethanol was added to obtain a curing solution containing anhydrous ethanol;
(6) Preparation of preservation solution:
The purchased soybean oil (or tea oil, corn oil, peanut oil, rapeseed oil, cottonseed oil or other oils for injection) or liquid paraffin for injection was used as a preservation solution;
(7) Preparation of mixed solution:
The sodium alginate solution and the moxifloxacin solution prepared above were mixed and stirred uniformly to obtain a mixed solution.
4. Preparation of microspheres:
The above-obtained mixed solution was aspirated by a sterile syringe, and dripped into the above-obtained curing solution through the high voltage electrostatic multi-head microsphere liquid drop generating device, microspheres or micro-gel beads with different particle size ranges were prepared as required, and the resulting sodium alginate crosslinked moxifloxacin microspheres or micro-gel beads sank into the bottom of the container.
The high voltage electrostatic multi-head microsphere generating device comprises: a high voltage electrostatic generating device, propulsion pump, ejecting head, sterile container, positive and negative electrodes, sterile syringes of various models, and a lifting device. The high voltage electrostatic multi-head generating device has two electrodes of positive and negative electrodes in every group, the propulsion pump is connected to the sterile syringe and the ejecting head, the positive electrode is connected to the ejecting head, the negative electrode is connected to the stainless steel wire immersed in the curing solution, and the stainless steel wire is connected to the sterile container, and the lifting device for adjusting distance is under the stainless steel wire and the sterile container.
Particle sizes of said microspheres or micro-gel beads preserved in the preservation solution are as follows: 50˜100 μm, 50˜150 μm, 50˜200 μm, 100˜300 μm, 150˜450 μm, 300˜500 μm, 500˜700 μm, 700˜900 μm or 900˜1,250 μm. After the upper layer of the solution in the above-mentioned container was decanted, the microspheres or micro-gel beads were washed with physiological saline for immediate use.
The upper layer solution of the above-obtained microspheres was decanted, and the resulting sodium alginate microspheres containing the moxifloxacin anti-tuberculosis drug was dried (the method of freeze drying or oven drying was used to prepare dry spheres) to obtain powdered particles; the particle sizes of the powdered particles are in the range of 10˜50 μm, 25˜50 μm, 50˜100 μm, 100˜350 μm, 300˜550 μm or 500˜750 μm; the powdered particles were sealed for preservation, and before use, the powdered particles were soaked with physiological saline for a few minutes to be reconstituted to wet spheres.
Patients with pulmonary tuberculosis were treated by the method of interventional radiology or bronchoscopic intervention, wherein a catheter was inserted into the opening of target organ segment, a guide wire was introduced under monitoring by X-ray, and artery angiography was performed when the catheter was embedded into the blood vessel lumen. According to the findings shown in angiography, continuous photographs confirmed that the front end of the catheter was fixed, the guide wire was exited, and the catheter was retained, and the appropriate particle size range was selected for the above-mentioned sodium alginate crosslinked moxifloxacin microspheres; the sodium alginate crosslinked moxifloxacin microspheres (wet spheres) were washed with physiological saline for three times, generally 500˜700 μm microspheres can produce better effect, then an appropriate amount of contrast agent was added and mixed uniformly, the mixture was slowly injected into the lesion site via the catheter under fluoroscopy until the flow rate of the contrast agent decreased significantly, and then embolization was completed. Further artery angiography was performed to evaluate embolization effect.
Example 2
Preparation of Sodium Alginate Crosslinked Moxifloxacin Anti-Tuberculosis Microsphere Vascular Embolic Agent
1. Treatment of glassware:
The cleaned glassware was dried out in the air and then placed and baked in the high-temperature oven (for sterilization and depyrogenation) to be used.
2. Selection of microsphere preparing device:
A high voltage electrostatic multi-head microsphere generating device, which can controllably prepare spheres with uniform size, is simple and convenient to operate, has high output, and easily implements mass production, was selected.
3. Method for preparing various reagents: (1) Preparation of sodium alginate solution:
10 g of sodium alginate was weighed and placed in a glassware, then 500 ml of physiological saline or water for injection was added into the glassware while stirring, magnetical stirring was performed until all the sodium alginate was dissolved to obtain a sodium alginate solution;
(2) Preparation of adsorbent:
Human serum albumin (or bovine serum albumin) was dissolved with water for injection at a ratio of 0.1˜10% (mass-volume percentage) to obtain an adsorbent, i.e., an albumin solution;
(3) Preparation of moxifloxacin anti-tuberculosis drug solution:
14 g of commercially available moxifloxacin was weighed, placed in a glassware, and dissolved with 50 ml of the human serum albumin or bovine serum albumin solution of 0.1˜10% (mass-volume percentage) by stirring to obtain a moxifloxacin anti-tuberculosis drug solution;
(4) Preparation of gelatin strengthening solution:
26 g of gelatin was placed in a glassware, 500 ml of physiological saline or water for injection was added into the glassware while stirring, magnetical stirring was performed until all the gelatin was dissolved to obtain a gelatin strengthening solution;
(5) Preparation of curing solution containing anhydrous ethanol:
200 g of calcium chloride or barium chloride or calcium lactate was weighed and placed in a glassware, and 4,000 ml of water for injection was added into the glassware while stirring, magnetical stirring was performed until the calcium compound was dissolved, and then 1,000 ml of anhydrous ethanol was added to obtain a curing solution containing anhydrous ethanol;
(6) Preparation of preservation solution:
The purchased soybean oil (or tea oil, corn oil, peanut oil, rapeseed oil, cottonseed oil or other oils for injection) or liquid paraffin for injection was used as a preservation solution;
(7) Preparation of mixed solution:
The sodium alginate solution and moxifloxacin anti-tuberculosis drug solution prepared above were mixed and stirred uniformly to obtain a mixed solution.
4. Preparation of microspheres:
The above-obtained mixed solution was aspirated by a sterile syringe, and dripped into the above-obtained curing solution through the high voltage electrostatic multi-head microsphere liquid drop generating device, microspheres or micro-gel beads within different particle size ranges were prepared as required, and the resulting sodium alginate crosslinked moxifloxacin microspheres or micro-gel beads sank into the bottom of the container.
The high voltage electrostatic multi-head microsphere generating device comprises: a high voltage electrostatic generating device, propulsion pump, ejecting head, sterile container, positive and negative electrodes, sterile syringes of various models, and a lifting device. The high voltage electrostatic multi-head generating device has two electrodes of positive and negative electrodes in every group, the propulsion pump is connected to the sterile syringe and the ejecting head, the positive electrode is connected to the ejecting head, the negative electrode is connected to the stainless steel wire immersed in the curing solution, and the stainless steel wire is connected to the sterile container, and the lifting device for adjusting distance is under the stainless steel wire and the sterile container.
Particle sizes of said microspheres or micro-gel beads preserved in the preservation solution are as follows: 50˜100 μm, 50˜150 μm, 50˜200 μm, 100˜300 μm, 150˜450 μm, 300˜500 μm, 500˜700 μm, 700˜900 μm or 900˜1,250 μm. After the upper layer of the solution in the above-mentioned container was decanted, the microspheres or micro-gel beads were washed with physiological saline for immediate use.
The upper layer solution of the above-obtained microspheres was decanted, and the resulting sodium alginate microspheres containing the moxifloxacin anti-tuberculosis drug was dried (the method of freeze drying or oven drying was used to prepare dry spheres) to obtain powdered particles; the particle sizes of the powdered particles are in the range of 10˜50 μm, 25˜50 μm or 50˜100 μm; 100˜350 μm, 300˜550 μm or 500˜750 μm; the powdered particles were sealed for preservation, and before use, the powdered particles were soaked with physiological saline for a few minutes to be reconstituted to wet spheres.
Patients with pulmonary tuberculosis cavity were treated by the method of interventional radiology or bronchoscopic intervention, wherein a catheter was inserted into the opening of target organ segment, a guide wire was introduced under monitoring by X-ray, and artery angiography was performed when the catheter was embedded into the blood vessel lumen. According to the findings shown in angiography, continuous photographs confirmed that the front end of the catheter was fixed, the guide wire was exited, and the catheter was retained, and the appropriate particle size range was selected for the above-mentioned sodium alginate crosslinked moxifloxacin microspheres; the sodium alginate crosslinked moxifloxacin microspheres (wet spheres) were washed with physiological saline for three times, generally 700˜900 μm microspheres can produce better effect, then an appropriate amount of contrast agent was added and mixed uniformly, the mixture was slowly injected into the lesion site via the catheter under fluoroscopy until the flow rate of the contrast agent decreased significantly, and then embolization was completed. Further artery angiography was performed to evaluate embolization effect.
Results of clinical trials show that the drug microspheres of the present invention can be used for embolizing peripheral small artery blood vessel, after embolization, no pressure difference is generated between two ends of potential collateral circulation blood vessels, it is not easy to form a secondary collateral circulation, and the drug can be delivered to the target organs and target cells; when applied, the drug can be highly concentrated in the lesion site, and only minimal amount of drug exist in the normal site, the therapeutic effect is improved and the systemic toxic and side effect is reduced, primary blood supply to sites of tuberculosis is effectively cut off, the flushing action of blood flow on the drug is blocked, and the duration of action of the drug is extended, so that the therapeutic purpose can be achieved.
Example 3
Preparation of Sodium Alginate Crosslinked Moxifloxacin Anti-Tuberculosis Microsphere Vascular Embolic Agent
1. Treatment of glassware:
The cleaned glassware was dried out in the air and then placed and baked in the high-temperature oven (for sterilization and depyrogenation) to be used.
2. Selection of microsphere preparing device:
A high voltage electrostatic multi-head microsphere generating device, which can controllably prepare spheres with uniform size, is simple and convenient to operate, has high output, and easily implements mass production, was selected.
3. Method for preparing various reagents: (1) Preparation of sodium alginate solution:
15 g of sodium alginate was weighed and placed in a glassware, then 500 ml of physiological saline or water for injection was added into the glassware while stirring, magnetical stirring was performed until all the sodium alginate was dissolved to obtain a sodium alginate solution;
(2) Preparation of adsorbent:
Human serum albumin (or bovine serum albumin) was dissolved with water for injection at a ratio of 0.1˜10% (mass-volume percentage) to obtain an adsorbent, i.e., an albumin solution;
(3) Preparation of moxifloxacin anti-tuberculosis drug solution:
10 g of commercially available moxifloxacin was weighed, placed in a glassware, and dissolved with 50 ml of the human serum albumin or bovine serum albumin solution of 0.1˜10% (mass-volume percentage) by stirring to obtain a moxifloxacin anti-tuberculosis drug solution;
(4) Preparation of gelatin strengthening solution:
20 g of gelatin was placed in a glassware, 500 ml of physiological saline or water for injection was added into the glassware while stirring, magnetical stirring was performed until all the gelatin was dissolved to obtain a gelatin strengthening solution;
(5) Preparation of curing solution containing anhydrous ethanol:
200 g of calcium chloride or barium chloride or calcium lactate was weighed and placed in a glassware, and 4,000 ml of water for injection was added into the glassware while stirring, magnetical stirring was performed until the calcium compound was dissolved, and then 1,000 ml of anhydrous ethanol was added to obtain a curing solution containing anhydrous ethanol;
(6) Preparation of preservation solution:
The purchased soybean oil (or tea oil, corn oil, peanut oil, rapeseed oil, cottonseed oil or other oils for injection) or liquid paraffin for injection was used as a preservation solution;
(7) Preparation of mixed solution:
The sodium alginate solution and moxifloxacin anti-tuberculosis drug solution prepared above were mixed and stirred uniformly to obtain a mixed solution.
4. Preparation of microspheres
The above-obtained mixed solution was aspirated by a sterile syringe, and dripped into the above-obtained curing solution through the high voltage electrostatic multi-head microsphere liquid drop generating device, microspheres or micro-gel beads within different particle size ranges were prepared as required, and the resulting sodium alginate crosslinked moxifloxacin microspheres or micro-gel beads sank into the bottom of the container.
The high voltage electrostatic multi-head microsphere generating device comprises: a high voltage electrostatic generating device, propulsion pump, ejecting head, sterile container, positive and negative electrodes, sterile syringes of various models, and a lifting device. The high voltage electrostatic multi-head generating device has two electrodes of positive and negative electrodes in every group, the propulsion pump is connected to the sterile syringe and the ejecting head, the positive electrode is connected to the ejecting head, the negative electrode is connected to the stainless steel wire immersed in the curing solution, and the stainless steel wire is connected to the sterile container, and the lifting device for adjusting distance is under the stainless steel wire and the sterile container.
Particle sizes of said microspheres or micro-gel beads preserved in the preservation solution are as follows: 50˜100 μm, 50˜150 μm, 50˜200 μm, 100˜300 μm, 150˜450 μm, 300˜500 μm, 500˜700 μm, 700˜900 μm or 900˜1,250 μm. After the upper layer of the solution in the above-mentioned container was decanted, the microspheres or micro-gel beads were washed with physiological saline for immediate use.
The upper layer solution of the above-obtained microspheres was decanted, and the resulting sodium alginate microspheres containing the moxifloxacin anti-tuberculosis drug was dried (the method of freeze drying or oven drying was used to prepare dry spheres) to obtain powdered particles; the particle sizes of the powdered particles are in the range of 10˜50 μm, 25˜50 μm or 50˜100 μm; 100˜350 μm, 300˜550 μm or 500˜750 μm; the powdered particles were sealed for preservation, and before use, the powdered particles were soaked with physiological saline for a few minutes to be reconstituted to wet spheres.
Patients with mass hemoptysis of pulmonary tuberculosis were treated by the method of interventional radiology or bronchoscopic intervention, wherein a catheter was inserted into the feeding artery in the target organ, and artery angiography was performed. According to the findings shown in angiography, the appropriate particle size range was selected for the above-mentioned sodium alginate microspheres containing moxifloxacin. The sodium alginate crosslinked moxifloxacin microspheres (wet spheres) were washed with physiological saline for three times, generally 500˜700 μm or 700˜900 μm microspheres can produce better effect, then an appropriate amount of contrast agent was added and mixed uniformly, the mixture was slowly injected into the lesion site via the catheter under fluoroscopy until the flow rate of the contrast agent decreased significantly, and then embolization was completed. Further artery angiography was performed to evaluate embolization effect.
Results of clinical trials show that the solvent used in the present invention is effective and safe, when the catheter is inserted into the target blood vessel, microspheres containing the drug is mixed with the contrast agent by a syringe after angiography, and when the mixture of the microspheres and contrast agent is slowly injected into the catheter, no aggregation occurs and no catheters is blocked. Particle sizes of said drug microspheres are appropriate (generally 500˜700 μm or 700˜900 μm microspheres can produce better effect), and the drug microspheres have advantages such as, having good biocompatibility, being nontoxic and harmless to human bodies, and non-immunogenic, having affinity with the drug carried, low drug toxic and side effects, high drug concentration and high utilization.
Example 4
Preparation of Sodium Alginate Crosslinked Moxifloxacin Anti-Tuberculosis Microsphere Vascular Embolic Agent
1. Treatment of glassware:
The cleaned glassware was dried out in the air, and then placed and baked in the high-temperature oven (for sterilization and depyrogenation) to be used.
2. Selection of microsphere preparing device:
A high voltage electrostatic multi-head microsphere generating device, which can controllably prepare spheres with uniform size, is simple and convenient to operate, has high output, and easily implements mass production, was selected.
3. Method for preparing various reagents: (1) Preparation of sodium alginate solution:
20 g of sodium alginate was weighed and placed in a glassware, then 500 ml of physiological saline or water for injection was added into the glassware while stirring, magnetical stirring was performed until all the sodium alginate was dissolved to obtain a sodium alginate solution;
(2) Preparation of adsorbent:
Human serum albumin (or bovine serum albumin) was dissolved with water for injection at a ratio of 0.1˜10% (mass-volume percentage) to obtain an adsorbent, i.e., an albumin solution;
(3) Preparation of moxifloxacin anti-tuberculosis drug solution:
22 g of commercially available moxifloxacin was weighed, placed in a glassware, and dissolved with 50 ml of the human serum albumin or bovine serum albumin solution of 0.1˜10% (mass-volume percentage) by stirring to obtain a moxifloxacin anti-tuberculosis drug solution;
(4) Preparation of gelatin strengthening solution:
22 g of gelatin was placed in a glassware, 500 ml of physiological saline or water for injection was added into the glassware while stirring, magnetical stirring was performed until all the gelatin was dissolved to obtain a gelatin strengthening solution;
(5) Preparation of curing solution containing anhydrous ethanol:
200 g of calcium chloride or barium chloride or calcium lactate was weighed and placed in a glassware, and 4,000 ml of water for injection was added into the glassware while stirring, magnetical stirring was performed until the calcium compound was dissolved, and then 1,000 ml of anhydrous ethanol was added to obtain a curing solution containing anhydrous ethanol;
(6) Preparation of preservation solution:
The purchased soybean oil (or tea oil, corn oil, peanut oil, rapeseed oil, cottonseed oil or other oils for injection) or liquid paraffin for injection was used as a preservation solution;
(7) Preparation of mixed solution:
The sodium alginate solution and moxifloxacin anti-tuberculosis drug solution prepared above were mixed and stirred uniformly to obtain a mixed solution.
4. Preparation of microspheres:
The above-obtained mixed solution was aspirated by a sterile syringe, and dripped into the above-obtained curing solution through the high voltage electrostatic multi-head microsphere liquid drop generating device, microspheres or micro-gel beads within different particle size ranges were prepared as required, and the resulting sodium alginate crosslinked moxifloxacin microspheres or micro-gel beads sank into the bottom of the container.
The high voltage electrostatic multi-head microsphere generating device comprises: a high voltage electrostatic generating device, propulsion pump, ejecting head, sterile container, positive and negative electrodes, sterile syringes of various models, and a lifting device. The high voltage electrostatic multi-head generating device has two electrodes of positive and negative electrodes in every group, the propulsion pump is connected to the sterile syringe and the ejecting head, the positive electrode is connected to the ejecting head, the negative electrode is connected to the stainless steel wire immersed in the curing solution, and the stainless steel wire is connected to the sterile container, and the lifting device for adjusting distance is under the stainless steel wire and the sterile container.
Particle sizes of said microspheres or micro-gel beads preserved in the preservation solution are as follows: 50˜100 μm, 50˜150 μm, 50˜200 μm, 100˜300 μm, 150˜450 μm, 300˜500 μm, 500˜700 μm, 700˜900 μm or 900˜1,250 μm. After the upper layer of the solution in the above-mentioned container was decanted, the microspheres or micro-gel beads were washed with physiological saline for immediate use.
The upper layer solution of the above-obtained microspheres obtained above was decanted, and the resulting sodium alginate microspheres containing the moxifloxacin anti-tuberculosis drug was dried (the method of freeze drying or oven drying was used to prepare dry spheres) to obtain powdered particles; the particle sizes of the powdered particles are in the range of 10˜50 μm, 25˜50 μm or 50˜100 μm; 100˜350 μm, 300˜550 μm or 500˜750 μm; the powdered particles were sealed for preservation, and before use, the powdered particles were soaked with physiological saline for a few minutes to be reconstituted to wet spheres.
The method of interventional radiology or bronchoscopic intervention is used to treat patients with tuberculosis other than pulmonary tuberculosis, such as renal tuberculosis, thyroid tuberculosis, cervical lymph node tuberculosis, genital tuberculosis (fallopian tube tuberculosis, endometrium tuberculosis, testis tuberculosis, epididymis tuberculosis), pericardial tuberculosis, chest wall tuberculosis, pleural tuberculosis and other tuberculosises in the body.
A catheter was inserted into the feeding artery in the target organ, and artery angiography was performed. According to the findings shown in angiography, the appropriate particle size range was selected for the above-mentioned sodium alginate microspheres containing moxifloxacin. The sodium alginate crosslinked moxifloxacin microspheres (wet spheres) were washed with physiological saline for three times, generally 300˜500 μm microspheres can produce better effect, then an appropriate amount of contrast agent was added and mixed uniformly, the mixture was slowly injected into the lesion site via the catheter under fluoroscopy until the flow rate of the contrast agent decreased significantly, and then embolization was completed. Further artery angiography was performed to evaluate embolization effect. Results of clinical trials show that the solvent used in the present invention is effective and safe, local concentration of the drug is increased while the total amount of drug is decreased, the incidence of systemic toxic and side effect is reduced; when the biodegradable microspheres containing the drug is implanted into the tuberculosis, the release rate of the drug can approach zero-order release rate, stable drug concentration can be maintained, no burst releasing effect is produced, and it is not necessary to remove microspheres by operation.
Those skilled in the art can understand that the description hereinbefore are only preferred embodiments of the present invention and not intended to limit the present invention. Although the present invention is illustrated in detail with reference to the aforementioned embodiments, those skilled in the art can still modify the technical solutions of the foregoing embodiments or perform equivalent substitution on part of the technical features. Any modifications, equivalent substitutions, improvements and the like made within the spirit and principle of the present invention shall be included within the protection scope of the present invention. | A sodium alginate crosslinked slow-released moxifloxacin microsphere, the preparation method of the microsphere, a vascular target embolus containing the microsphere and the use of the microsphere in preparing the vascular target embolus. The microsphere contains moxifloxacin, a drug carrier, a adsorbent, a reinforcing agent and a solidifying agent, wherein the drug carrier is sodium alginate, the adsorbent is albumin prepared from human plasma or bovine serum albumin, the reinforcing agent is gelatin or hyaluronic acid, and the solidifying agent is a divalent metal cation chosen from calcium salt or barium salt. | 0 |
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation-in-part of U.S. Ser. No. 798,474, filed Nov. 15, 1985, now abandoned.
BACKGROUND OF THE INVENTION
Organic polymers with a conjugated backbone form an important class of electronically conducting materials. Conduction mechanism in these types of polymers involve π-electrons which overlap along the conjugated chain to form a π-conduction band. These materials are intrinsically semiconductors, and can be made highly conducting only after chemical doping. To date semiconducting polyacetylene remains the most extensively studied of the conjugated polymers due to the availability of its flexible films, the high conductivity upon doping, and the reversibility in the electrochemical oxidation (p-type doping)--reduction (n-type doping) process. The chemical doping of polyacetylene film with electron acceptors such as AsF 5 and iodine, or electron donors such as sodium, gives values of conductivity up to 10 3 Ω -1 cm -1 at room temperature. Unfortunately, there are some practically inconvenient features associated with polyacetylene. Probably the most disadvantageous feature of all is its inherent inconvenient instability towards atmospheric oxidation. This instability hindered the scientific study and its possible technological exploitation. Therefore, a great interest has been generated in the exploration of related polymers with a great oxidative stability as well as thermal stability and processability while retaining the interesting electrical properties.
Based on these considerations, the most pronounced polymers belong to the category of aromatic polyarene polymers. Some examples are: poly(paraphenylene), Shacklette, L. W., Chance, R. R., Ivory, D. M.; Miller, G. G.; Baughman, R. H., Synth. Met., 1980, 1, 307; polypyrrole, Diaz, A, Kanazawa, K. K.; Gardini, G. P., J. Chem. Soc., Chem. Commun., 1979, 635; poly(2,5-thienylene), Yamamoto, T., Sanechika, K., Yamamoto, A., J. Polym. Sci., Polym. Lett. Ed., 1980, 18, 9; Lin, J., Dudek, L., J. Polym. Sci., Polym. Chem. Ed., 1980, 18, 2689; poly(phenylquinoline), Wrasidlo, W., Norris, S. O., Wolfe, J. F., Katto, T., Stille, J. K., Macromolecules, 1976, 9, 512, polyselenophene, Yoshino, K., Kaneto, K., Inoue, S., Tsukagoshi, K., Jap. J. Appl. Phys., 1983, 22, L701, and polynaphthalene, Aldissi, M., Liepins, R., J. Chem. Soc., Chem. Commun., 1984, 255. Among these polyaromatics, poly(phenylquinoline), and its derivatives are generally the most thermal oxidative stable polymers. Films based on these poly(phenylquinoline) derivatives have been reported to exhibit conductivities of up to the order of 50Ω -1 cm -1 upon doping with sodium, Tunney, S. E.; Suenaga, J.; Stille, J. K., Macromolecules, 1983, 16, 1398, Denisevich, P.; Papir, Y. S.; Kurkov, V. P.; Current, S. P.; Schroeder, A. H.; Suzuki, S., Polym. Prepr., Am. Chem. Soc., Div. Polym. Chem., 1983, 24, 330-1, a seventeen orders of magnitude increase in conductivity compared to the undoped material. Surprisingly, to date the nonsubstituted polyquinoline of the present invention has not yet been made in spite of many substituted polyquinoline derivatives having been successfully synthesized, Stille, J. K., Macromolecules, 1981, 14, 870-80.
It is known that polyquinoline derivatives can be prepared by a Friedlander synthesis, Friedlander, P. Chem. Ber. 1882, 15, 2572, which is a base catalyzed reaction between 2-aminobenzaldehyde and acetaladehyde. This type of reaction was found to undergo a far better satisfactory result with an acid catalyst of poly(phosphoric acid) than base catalysis in the polymer synthesis with a higher molecular weight product and a higher yield. Thus, homopolymer or copolymer of quinoline derivatives can be readily prepared by a condensative cyclization reaction between aromatic o-amino ketone and ketomethylene compounds to construct quinoline moieties. However, this method is most suitable for the synthesis of substituted polyquinolines but not for the nonsubstituted polyquinoline due to the side reaction of the aldehyde functionality if an o-amino aldehyde is used instead of o-amino ketone.
SUMMARY OF THE INVENTION
The present invention is a process for polymerizing certain aromatic nitrogen heterocyclic compounds under catalytic conditions with a metal sulfide catalyst wherein the metal is selected from the group consisting of transition metals of Group VI, VII and VIII of the periodic table or mixtures thereof. A preferred catalyst is rhenium sulfide. These compounds include tetrahydroquinoline, 3-monosubstituted trihydroquinoline, 4-monosubstituted trihydroquinoline, and 3,4-disubstituted dihydroquinoline, where the substitution includes any organic alkyl or aryl group.
In a preferred embodiment, the aromatic nitrogen heterocyclic compound is tetrahydroquinoline ##STR1## and the reaction product is polyquinoline ##STR2## where the valence bond may be attached at any ring position and x may be any integer ≧2. Doped polyquinoline can be used as an electrical conductor or as a photoconductor in various applications, such as plastic battery, photoconductive cells, light weight conductor, and magnetic shielding material.
DESCRIPTION OF THE PREFERRED EMBODIMENT
In the preferred embodiment, a nonsubstituted polyquinoline is prepared by a dehydrogenative polymerization of tetrahydroquinoline (THQ) in the presence of rhenium sulfide catalyst at the refluxing temperature of THQ in a high yield (>90%). The new method provides a facile one-step synthesis from a commercially available starting material, THQ. It certainly offers an advantage over the Friedlander synthesis since no more complicated monomer synthesis is necessary.
Commercial grade tetrahydroquinoline was used directly without further purification. In general, an amorphous powder of rhenium sulfide with a surface area of 20-30 m 2 /g is used. Crystalline rhenium sulfides are prepared by a thermal treatment of amorphous rhenium sulfides at an elevated temperature between 400° C. and 800° C. Suitable rhenium sulfide catalysts may be prepared as described in U.S. Pat. No. 4,308,171.
EXAMPLE
General Procedure for Dehydrogenative Polymerization Reaction
A single-neck round bottle flask equipped with a condensor and an inert gas bubbler was charged with a solution of tetrahydroquinoline (25 ml, 98%, 0.19 mol) and a proper amount of rhenium sulfide catalyst (500 mg to 1 g). The suspension mixture was maintained under an argon atmospheric pressure and heated in the heating mantle at 150° C. initially and then at 200° to 300° C. for two days to one week. A preferred temperature is about 270° C.
At this temperature, a gentle reflux of tetrahydroquinoline was obtained. At the end of the reaction, the resulting product was cooled to the room temperature to give a dark solid. It was transferred into a solution mixture of diethylether-hexane/1:3 (300 ml). The resulting suspension solution was stirred overnight at the room temperature. The insoluble solid was then filtered and washed with another portion of diethylether-hexane/1:3 (50 ml). A repeated methylene chloride extraction of the solid separated the product into a methylene chloride soluble fraction and a methylene chloride insoluble fraction. The methylene chloride soluble fraction was dried on a rotary evaporator to give an orange-brown thick paste which solidified on standing. It was then chromatographed on a silica gel column using a solvent mixture of ethyl-acetate-hexane/1:3 as eluent initially. The solvent composition was changed slowly to ethylacetate-methylene chloride-hexane/1:1:2. The elution of column chromatography was continued until no more product in the eluent can be detected. Combined solvents were evaporated to afford a yellow solid of the soluble polyquinoline in a 54% yield (13.5 g).
The methylene chloride insoluble fraction was treated with a highly concentrated aqueous hydrochloric acid solution of a ratio of conc. HCl-H 2 O/1:1 (500 ml) overnight with a vigorous stirring. The resulting thick solution was diluted with water (500 ml) and then filtered through a sintered glass frit under vacuum. The insoluble black solid was washed with more portions of dilute hydrochloric acid and water to give a black recovered catalyst (580 mg to 1.2 g).
The remaining hydrochloric acid solution was neutralized by an addition of sodium hydroxide pellets to afford a precipitation. The filtration of precipitates gave a gray solid of the methylene chloride insoluble polyquinoline in a 36% yield (9 g). Therefore, the combined fractions of polyquinoline gave a total yield of higher than 90%.
Identification of Polymer Structure
The structure of the polymer obtained from the catalytic tetrahydroquinoline polymerization is elucidated mainly based on the soluble oligmer isolated from the bulk polymer product. Elemental analysis formulates the polymer as C 9 H 5+x N of the polyquinoline composition. The value of x varies as a function of the degree of polymerization with a hydrogen atom as an end group. Mass spectrum (EI) of the methylene chloride soluble oligmer shows a clear consecutive weight loss of 127 which matches with the unit weight of quinoline in the polymer. It also shows ion fragmentations of 128, 255, 382, 509, and so forth corresponding to the monomeric, dimeric, trimeric, and tetrameric polyquinoline fragment.
Infrared spectrum of both oligmer and bulk polymer shows a new band at 821 cm -1 corresponding to the C--H out-of-plane deformation of heterocyclic ring moiety of quinoline in addition to a band at 746 cm -1 of the C--H out-of-plane deformation of benzene ring moiety of quinoline when it is compared with the IR spectrum of tetrahydroquinoline. It indicates that the heterocyclic ring moiety of polymer has been fully dehydrogenated. This observation is consistent with the disappearance of a band at 2800-2930 cm -1 in the IR spectrum of polymer corresponding to the aliphatic C--H stretch in THQ molecule.
The high aromaticity nature of the polymer is further confirmed by the NMR study. Both 1 H-NMR and 13 C-NMR of the polymer isolated as a methylene chloride insoluble acetic acid (CD 3 CO 2 D) soluble fraction contains either none or only a trace of aliphatic hydrogens and aliphatic carbons. The most characteristic peak in the proton NMR is the doublet peak at 9.74 ppm (H=2 Hz) which is corresponding to the α (position 2) proton adjacent to the nitrogen atom in the quinoline unit. Due to the much lower intensity of this peak relative to the intensity of the rest of the aromatic protons combined, it indicates that one of the ring conjunctions has occurred at the α carbon next to the nitrogen atom in the polymer. Meanwhile, based on the calculation of the intensity ratio between that of the peak at 9.74 ppm and peaks at 7.46 ppm to 8.95 ppm, we obtain an average repeating quinoline unit of seven in the methylene chloride insoluble acetic acid soluble fraction of the polymer. It was found that the methylene chloride soluble fraction of polymer still contains a small percentage of incompletely dehydrogenated hydrocarbons. The amount of the aliphatic moiety (carbon) is estimated to be less than 3% from the calculation of the integration of aliphatic hydrogens in the 1 H-NMR (dissolved in CDCl 3 ). However, the 13 C-NMR of this fraction provides less clear evidence of the existence of aliphatic carbons in the spectrum. In general, partially saturated heterocyclics has a higher polarity than the fully aromatized one. Thus, an aliphatic hydrocarbon free polyquinoline can be isolated from this fraction by the collection of early eluents of chromatography as identified by 1 H-NMR (dissolved in CDCl 3 ). With the same technique of molecular weight estimation from 1 H-NMR as described previously, the methylene chloride soluble fraction of polymer consists of an average repeating quinoline unit 5.6. Finally, the acetic acid insoluble fraction of polymer is believed to have a higher molecular weight than the soluble one.
The origin of the dehydrogenative polymerization of tetrahydroquinoline is studied by the reaction of various compounds of THQ analog with rhenium sulfide. As a result, no polymer was obtained in the reaction with pyrrolidine, piperidine, tetrahydrothiophene, tetrahydronaphthalene, and quinoline. It implied that a combination of aromatic hydrocarbons with an active hydrogen atom on the adjacent heteroatom is an ideal system for the polymerization to occur. Interestingly, quinoline itself did not polymerize in the presence of rhenium sulfide at 260° C. It clearly indicates that a stable aromatic quinoline ring gives no contribution to the polymerization mechanism.
The chemical reaction of tetrahydroquinoline occurs apparently on the surface of rhenium sulfide since a high crystalline, low surface area rhenium sulfide gave a much less satisfied result with a low yield of polymer. We found that 2 to 4 weight percent is the ultimate amount of amorphous catalyst required for a complete reaction. Upon the decrease of catalyst concentration, both the yield and the aromaticity decline. For example, at a catalyst concentration of 0.4% wt. level, we observe only a methylene chloride insoluble polyquinoline in 10% yield and a soluble polymer containing a high intensity of aliphatic hydrocarbon in 27% yield. Furthermore, no polymer is obtained with a 0.04% wt. of catalyst concentration. | A new method for the preparation of polyquinoline is discovered. Upon the treatment of tetrahydroquinoline (THQ) with ReS 2+x at the refluxing temperature of THQ, a nearly quantitative yield of polyquinoline is obtained and characterized. | 2 |
RELATED APPLICATIONS
[0001] This is a continuation of U.S. patent application Ser. No. 10/946,252, filed on Sep. 21, 2004, which is a continuation of U.S. patent application Ser. No. 10/945,223, filed on Sep. 20, 2004, issued as U.S. Pat. No. 7,119,689 on Oct. 10, 2006, which claims the benefit of U.S. Provisional Patent Applications Ser. No. 60/504,170 filed Sep. 19, 2003 and Ser. No. 60/589,118, filed Jul. 19, 2004, all of which are incorporated by reference herein in their entireties.
BACKGROUND
[0002] 1. Field of the Invention
[0003] The invention relates in general to the field of waste disposal systems, and in particular to a system for sorting medical waste for disposal.
[0004] 2. Description of the Related Art
[0005] The Environmental Protection Agency (EPA) enforces the Resource Conservation & Recovery Act (RCRA) which was enacted in 1976 in order to control the disposal of harmful or hazardous waste materials. There are currently over 100,000 drugs commercially available in the United States, of which about 14,000 are considered hazardous by RCRA requirements. A typical medium size hospital utilizes thousands of different drugs in a year of which hundreds are considered hazardous. The EPA is increasingly enforcing hospitals' compliance with the RCRA requirements because it has been shown in several studies that the 72 million pounds of pharmaceutical waste generated each year by hospitals is contributing to the pollution of groundwater and endocrine system damage in humans and other species. In addition, many organizations including Hospital for a Healthy Environment (H2E) and Joint Council for Accreditation of Healthcare Organizations (JCAHO) are pressing hospitals to be more environmentally friendly. In view of these changes, hospitals are increasing efforts to audit their own compliance with the laws. As a result, these hospitals are becoming more aware of the difficulty of sorting the numerous pharmaceutical waste streams that the EPA, Department of Transportation (DOT), Drug Enforcement Administration (DEA), and some states require.
[0006] More than 3.2 million tons of medical waste is generated by hospitals, medical clinics and pharmaceutical manufacturers each year. Half of this waste is considered infectious. Most of the infectious waste was treated in over 2400 incinerators throughout the country, until 1998 when the EPA began to enforce tough environmental emission laws that have reduced the number of incinerators to just over a hundred nationwide. Now much of the infectious waste is hauled to these remaining incinerators, often a substantial distance, or is treated by alternative technologies such as autoclaves and chemical processors. There is very little choice for hospitals because of the upfront cost and large footprint of the processing equipment. Although many companies have offered different kinds of equipment, the prices vary from a few hundred thousand dollars for smaller units to a few million for large units. Because of the long cycling times to decontaminate the waste, the equipment typically is very large in order to provide acceptable throughput. There are also several companies that provide a service to hospitals by utilizing chemical processors mounted on trucks. They go to a facility and decontaminate the infectious waste, allowing the treated waste to be hauled to a local landfill. There are concerns that this technology may not completely treat the waste in all circumstances and the chemical residue left after processing may remain an ecological issue.
[0007] Increasingly, hospitals are required to comply with the recent and projected enforcement of federal and state hazardous pharmaceutical waste regulations. Currently, clinicians must manually sort pharmaceutical waste streams into different colored containers for proper disposal of the separate waste streams. It is often not clear to a clinician which pharmaceuticals or waste materials are hazardous simply by looking at the container. Such confusion may lead to clinicians throwing hazardous drugs in non-hazardous containers such as sharps containers, infectious waste bags, non-hazardous pharmaceutical containers or simply down the drain.
SUMMARY OF THE INVENTION
[0008] There remains a need for a system for allowing clinicians to more easily sort medical waste items for appropriate disposal. There also remains a need for an automated system of waste disposal that encourages and facilitates hospital compliance with the relevant federal and state regulations.
[0009] Several embodiments of the present application describe systems and devices to sort and process infectious and pharmaceutical waste streams. Embodiments of a medical waste sorting system advantageously provide a labor savings for doctors, nurses and other clinicians by taking the bulk of the decision making associated with sorting medical waste away from the clinician. In one embodiment, a medical waste sorting system is provided, which will help clinicians conveniently comply with the recent and projected enforcement of federal and state hazardous waste laws. In some embodiments, the system can be configured to scan a bar code, RFID tag, or other system for identifying a spent drug. The spent drug can then be classified into an appropriate waste category, and a door can be automatically opened to provide access to a unique waste container for convenient disposal of the drug in compliance with applicable regulations.
[0010] According to another embodiment, a system is provided which will render infectious hospital or laboratory waste non-infectious. This embodiment will provide an economical service to a hospital by utilizing a self-contained truck-mounted version. Alternatively, a stand alone version can be made available for hospital purchase.
[0011] In another embodiment, a system for treating hazardous medical waste items in order to render them non-hazardous is provided.
[0012] In addition to the need for medical and pharmaceutical waste sorting, there exists a need to improve areas of water quality analysis and workplace safety. These areas include sampling water quality throughout the hospital to pinpoint inappropriate dumping of hazardous materials down the drain and improved programs that reduce hospital worker exposure to hazardous materials in the workplace.
[0013] In one embodiment, a system for sorting waste is provided. The system of this embodiment comprises a plurality of containers associated with a plurality of waste categories. A waste item identification device is configured to determine a qualitative parameter of an item of medical waste. A database is provided with medical waste item classification information. A control system is programmed to compare the qualitative parameter of the waste item to information contained in the database in order to assign the item to a medical waste category. The system also includes a sorting mechanism configured to place the item into one of the containers based on the medical waste category.
[0014] In another embodiment, a system for sorting waste comprises a waste item identification means for identifying a qualitative parameter of an item of medical waste, and a database means for classifying medical waste items into categories according to rules and regulations affecting the disposal of medical waste items. The system also includes control means for comparing the qualitative parameter of the waste item to information contained in the database, and for assigning the item to a unique medical waste category. A sorting means is also provided for placing the item into a container associated with the waste category.
[0015] In another embodiment, a system for determining the level of contents within a waste container is provided. The system of this embodiment comprises a plurality of containers, each one being associated with at least one of a plurality of a waste categories. Waste is placed in the containers based on a determination by a database that comprises medical waste classification information. At least one optical source is positioned on one side of at least one of the containers, and at least one optical detector is positioned on an opposite side of at least one of the containers. A processor is configured to determine a level of contents of a container by analysis of the data received from the optical detector.
[0016] Another embodiment of a system for determining the level of contents within a container comprises a means for containing waste items comprising a plurality of containers, and a means for producing an optical signal on one side of at least one of the plurality of containers. A means for receiving an optical signal is positioned on an opposite side of at least one of the containers, and means for processing signals from the respective means for producing and means for receiving is configured to determine a level of contents within at least one of the containers.
[0017] In another embodiment, a system comprises a container for storing sorted waste and a sensor configured to measure a presence of waste within the container without physically contacting the container. In another embodiment, a system comprises a means for storing sorted waste and a means for determining a quantity of waste within the container.
[0018] In another embodiment, a disposable container for use in a medical waste system comprises a plurality of walls defining an internal space and an opening configured to provide access to the internal space. An automatically operable door is configured to selectively occlude and reveal the opening, and the door is configured to be operated by a machine in which the container is placed. A machine-readable identification key is provided on at least a portion of the container. The machine-readable identification key bears a container type which defines a category of waste to be placed in the container.
[0019] In another embodiment, a disposable container for use in a medical waste system comprises a plurality of walls defining an internal space and an opening configured to provide access to the internal space. A flange extends from a portion of the container and comprises a pattern of holes configured to indicate a container type. The container type defines at least one category of waste to be placed in the container.
[0020] In another embodiment, a system comprises a plurality of disposable containers of different types. Each container type corresponds to a category of medical waste, and each container comprises a machine-readable key configured to indicate the container's type to a sorting machine. Each container also comprises an automatically-operable gate configured to selectively occlude and reveal an opening of the container. The gate is further configured to be automatically locked.
[0021] In another embodiment, a container for use in a medical waste system comprises a means for defining an internal space, and an aperture means for providing access to the internal space. An openable means for selectively occluding and revealing the aperture means is operable by an automated machine. A key means is also provided for indicating a container type to the machine.
[0022] In another embodiment, a disposable container for use in a medical waste system comprises a means for defining an internal space and a means for provide access to the internal space. A flange means extends from a portion of the container and indicates a category of waste to be placed in the container.
[0023] In another embodiment, a method of using a disposable container comprises receiving a disposable container in a sorting machine. The method is continued by reading an identification key on the container. The identification key defines a category of waste to be placed in the container. The method is continued by directing a user to place a plurality of waste items in the container and alerting a user when the container is full.
[0024] In another embodiment, a method of using a disposable container comprises receiving a plurality of disposable containers in a sorting machine, wherein each container corresponds to a waste category. The method further comprises reading an identification key on each container. The identification key defines a category of waste to be placed in the container. The method further comprises determining a waste category to which an item of waste belongs, providing access to a selected one of the containers, and directing a user to place the waste item in the selected container.
[0025] In another embodiment, a method of using a disposable container for sorting and disposing of medical waste comprises placing a plurality of containers in a sorting machine. Each container comprising an opening configured to provide access to an internal space. The method further comprises operating the machine to read an identification key from each container to determine a category of waste to be placed in each container and to automatically operate a door to selectively occlude and reveal the opening.
[0026] In another embodiment, a method of sorting medical waste comprises, in no particular order, receiving an identifier associated with waste to be disposed of, and retrieving (based on the identifier) information from a database. The information is derived from applicable rules regarding disposal of waste items. The method further comprises assigning the waste to a disposal category based on the information retrieved from the database, locating a container associated with the assigned disposal category, and facilitating disposal of the waste item into the container associated with the assigned disposal category.
[0027] In another embodiment, a method of sorting medical waste for disposal comprises identifying a plurality of containers in a sorting station and determining a waste category associated with each container, identifying an item of waste to be disposed of, and assigning the item to a waste category.
[0028] In another embodiment, a method of sorting medical waste comprises identifying a plurality of containers in a sorting station and determining at least one waste category associated with each container. The waste categories are ranked from least to most hazardous. The method further comprises identifying an item of waste to be disposed of, and assigning the item to a first waste category. The method further comprises determining whether a container associated with the first waste category is present in the sorting station, and if one is not present, re-assigning the waste item to a second waste category that is ranked more hazardous than the first waste category.
[0029] In another embodiment, a method of sorting medical waste items for disposal comprises identifying a plurality of containers in a sorting station and determining a waste category associated with each container. The waste categories are again ranked from least to most hazardous. The method further comprises identifying an item of waste to be disposed of, and assigning the item to a first waste category. The method further comprises determining whether a container associated with the first waste category is present in the sorting station, and if one is not present, directing a user to another sorting station which does have a container associated with the first waste category.
[0030] In another embodiment, a system for sorting medical waste items comprises a sorting station in electronic communication with a classification database which lists a plurality of waste item identifiers distributed into a plurality of waste categories. A plurality of containers are positioned in the sorting station. Each container is sized and configured to receive a plurality of medical waste items. A waste item identification device is configured to receive a waste item identifier from a waste item. A decision system is configured to classify the waste item into a waste category using the waste item identifier and information contained in the classification database. Each of the containers is associated with one of the waste categories, and the decision system is further configured to indicate into which of the containers a waste item should be deposited based on the waste category.
[0031] In another embodiment, a waste sorting and disposal system comprises a sorting and disposal station comprising a waste item identification device and a plurality of container compartments. The system also has a database which comprises medical waste item classification information derived from rules and regulations affecting the disposal of medical waste items, and a plurality of containers positioned in the container compartments. Each container comprises a machine-readable identification key and an automatically operable door formed integrally with the container. The station is configured to read each identification key upon placement of a container in a container compartment, and to selectively open and close the doors of each of the plurality of containers.
[0032] In another embodiment, a system for sorting medical waste items comprises a sorting station in electronic communication with a classification database which lists a plurality of waste item identifiers distributed into a plurality of waste categories. The waste categories are ranked from least to most hazardous. A plurality of containers are positioned in the sorting station, each container being sized and configured to receive a plurality of medical waste items. A waste item identification device is configured to receive a waste item identifier from a waste item, and a decision system is configured to assign the waste item to a waste category using the waste identifier and information contained in the classification database. Each of the containers is associated with at least one of the waste categories, and the decision system is further configured to indicate into which of the containers a waste item should be deposited based on the waste category. The decision system is further configured to open a container associated with a highest hazardousness level if the station does not include a container associated with the assigned category.
[0033] In another embodiment, a system for sorting medical waste items comprises a plurality of sorting stations in electronic communication with one another via a central processing unit in a centralized network. The sorting stations and the central processing unit are often physically separated from one another. A classification database, which lists a plurality of waste item identifiers distributed into a plurality of waste categories, resides in the central processing unit. Each sorting station comprises a plurality of containers, and each container is sized and configured to receive a plurality of medical waste items. A waste item identification device is configured to receive a waste item identifier from a waste item, and a decision system is configured to classify the waste item into a waste category using the waste identifier and information contained in the classification database. Each of the containers is associated with one of the waste categories, and the decision system is further configured to indicate into which of the containers a waste item should be deposited.
[0034] In another embodiment, a system for sorting medical waste items comprises a plurality of sorting stations in electronic communication with one another in a de-centralized network. The sorting stations are physically separated from one another, and a classification database resides on a data storage device in at least one of the stations. The database lists a plurality of waste item identifiers distributed into a plurality of waste categories. Each sorting station comprises a plurality of containers, and each container is sized and configured to receive a plurality of medical waste items. Each container is designated as a specific type which defines a group of items to be placed therein. A waste item identification device is configured to receive a waste item identifier from a waste item, and a decision system is configured to classify a waste item into a waste category using the waste identifier and information contained in the classification database. The decision system is further configured to indicate into which of the containers a waste item should be deposited.
[0035] In another embodiment, a method of sorting medical waste items comprises joining a plurality of physically separated sorting stations in electronic communication with one another in a network. The method further comprises joining each sorting station in electronic communication with a classification database which lists a plurality of waste item identifiers distributed into a plurality of waste categories. The method further comprises placing a plurality of containers in each station, each container being sized and configured to receive a plurality of medical waste items. The method further comprises providing each station with a waste item identification device configured to receive a waste item identifier from a waste item, and configuring a decision system in each station to classify waste items into waste categories using the waste identifier and information contained in the classification database.
[0036] In another embodiment, a waste system comprises a station comprising a waste identification device and a plurality of container compartments. A plurality of containers are positioned in the container compartments, and each container comprises a machine-readable identification key. The station is configured to read each identification key upon placement of a container in a container compartment.
[0037] In another embodiment, a waste system comprises a means for sorting waste comprising a means for identifying waste and means for supporting a container. Each one of a plurality of means for containing waste comprises a means for machine identification of the means for containing waste. The means for sorting further comprises a means for reading each means for machine identification upon placement of a means for containing in a means for supporting.
[0038] In another embodiment, a waste sorting and disposal system comprises a sorting and disposal station comprising a waste identification device and a plurality of container compartments A plurality of containers are positioned in the container compartments, each one comprising a machine-readable identification key which identifies a waste category defining characteristics of the waste to be placed in each container. The station is configured to read each identification key upon placement of a container in a container compartment, and the waste category of each container is independent of the container compartment in which each container is positioned.
[0039] In another embodiment, a sorting system for separating waste into a plurality of containers based on a classification of the waste item is provided. The system comprises a plurality of containers, each associated with at least one of a plurality of a waste categories. A waste detector is configured to identify waste presented to the detector. A sorting mechanism is configured to place waste into one of the containers based on information received from the waste detector. The system also comprises a sensor configured to determine whether at least one of the containers has waste therein.
[0040] In another embodiment, a sorting system for separating waste into a plurality of containers based on a classification of the waste is provided. The system of this embodiment comprises a plurality of containers, each associated with at least one of a plurality of a waste categories. A database comprises waste classification information derived from rules and regulations affecting the disposal of waste items. A waste detector is configured to identify waste presented thereto, and a sorting mechanism is configured to place waste into one of the containers based on information received from the waste detector. A sensor is configured to determine whether at least one of the containers has waste therein.
[0041] In another embodiment, a sorting system is provided for separating waste into a plurality of containers based on a classification of the waste. The system comprises a plurality of means for containing medical waste. Each of said means for containing medical waste is associated with at least one of a plurality of a waste categories. A means for identifying waste is provided, as is a means for sorting waste into one of the means for containing using information received from the means for identifying waste. The system also comprises a means for determining whether at least one of the containers has waste therein.
BRIEF DESCRIPTION OF DRAWINGS
[0042] FIG. 1 is a schematic illustration of one embodiment of medical waste sorting and disposal system including a plurality of interconnected sorting and disposal stations in a centralized network;
[0043] FIG. 2 is a schematic illustration of one embodiment of medical waste sorting and disposal system implemented in a decentralized network;
[0044] FIG. 3 is a perspective illustration of an embodiment of a wall-mounted sorting and disposal station;
[0045] FIG. 4 is a perspective illustration of one embodiment of a floor-standing sorting and disposal station;
[0046] FIG. 5 is a front perspective view of one embodiment of a rolling cart sorting and disposal station;
[0047] FIG. 6 is a rear perspective view of one embodiment of a rolling cart sorting and disposal station;
[0048] FIG. 7 is a perspective view of one embodiment of a sorting and disposal station incorporated into a rolling medications cart;
[0049] FIG. 8 is a rear perspective view of one embodiment of the cart of FIG. 7 ;
[0050] FIG. 9 is an alternative embodiment of the cart of FIG. 7 ;
[0051] FIG. 10 is a partially exploded perspective view of one embodiment of a sorting and disposal station comprising pivotable containers and sleeves;
[0052] FIG. 11 is a perspective view of one embodiment of a sorting and disposal station in the form of a convertible rolling cart in a first configuration;
[0053] FIG. 12 is a perspective view of one embodiment of the convertible rolling cart in a second configuration;
[0054] FIG. 13 is a perspective view of one embodiment of a disposable container and portions of an interface with a sorting and disposal station;
[0055] FIG. 14 is a perspective view of an alternative embodiment of a disposable container and portions of an interface with a sorting and disposal station;
[0056] FIG. 15 is a perspective view of an alternative embodiment of a disposable container;
[0057] FIG. 16 is a perspective view of an embodiment of a disposable container and an alternative embodiment of portions of an interface with a sorting and disposal station;
[0058] FIG. 17 is a perspective view of an embodiment of a disposable container and an alternative embodiment of portions of an interface with a sorting and disposal station;
[0059] FIG. 18 is a schematic side elevation view of an embodiment of a fill level sensor;
[0060] FIG. 19 is a block diagram of one embodiment of a fill-level detection system;
[0061] FIG. 20 is a an overview flow chart of one embodiment of a software algorithm for measuring a fill level of a container;
[0062] FIG. 21 is a detailed flow chart of one embodiment of a method of measuring a fill level of a container
[0063] FIG. 22 is a continuation of the flow chart of FIG. 5 ;
[0064] FIG. 22 a is an electronic schematic of one embodiment of an array of light detectors
[0065] FIG. 23 is a block diagram of an alternative embodiment of a level sensor system employing a video camera;
[0066] FIG. 23 a is an electronic schematic of one embodiment of an alternative embodiment employing a video system;
[0067] FIG. 24 is a flow chart illustrating one embodiment of a sorting algorithm for use by embodiments of a medical waste sorting and disposal system; and
[0068] FIG. 25 is a flow chart illustrating a container-checking subroutine for use by embodiments of a medical waste sorting and disposal system.
DETAILED DESCRIPTION
[0000] Waste Sorting And Disposal System
[0069] Embodiments of devices and methods for sorting a plurality of medical wastes will now be described with reference to the attached figures. In several embodiments, the waste sorting and disposal system is automated. In some embodiments, a medical waste sorting system comprising a plurality of individual sorting and disposal stations connected to one another via a centralized or de-centralized network is provided. Alternatively, a medical waste sorting system can comprise one or more stand-alone sorting and disposal stations configured to operate independently of any other device. Although some of the following embodiments are described in the context of individual stand-alone stations, it should be recognized that such individual stations can be connected in a networked system to provide additional functionality or to improve efficiency. Conversely, some embodiments are described below in the context of networked systems, certain features and advantages of which can be readily applied to individual stand-alone systems as will be clear to the skilled artisan. The term “sorting” is a broad term and shall be given its ordinary meaning and generally refers to the distribution of one or more waste items into one or more appropriate waste receptacles. The term “disposing” is also a broad term and shall be given its ordinary meaning and shall, in some embodiments, generally refer to the discarding or “throwing out” of one or more items of waste into an appropriate receptacle.
[0070] In one embodiment, a waste sorting and disposal station comprises a sorting station or machine, which includes a series of container positions or compartments, each compartment being configured to receive a disposable container for collecting waste belonging to a particular category or classification. Some embodiments of a sorting station comprise a waste-identifying device, a processor configured to carry out a waste-sorting algorithm, and a waste-sorting mechanism.
[0071] In some embodiments, a sorting machine comprises one or more sensors for determining the presence of a container, a type of container, and/or a volume or weight of a container. In another embodiment, the sorting machine includes one or more sensors (e.g., an optical sensor) to determine which container the item was deposited into and/or a time at which an item is deposited. Additionally, a sorting machine/station can include any of a variety of computer peripherals, such as user input devices (e.g., touch screens, keyboards, pointer devices, etc.), display devices, sound-producing devices (e.g., speakers or buzzers), or any other peripheral device.
[0072] In many embodiments, several container types are provided, each type being associated with a particular category or classification of pharmaceutical waste. For example, in some embodiments, container types can include sharps containers, chemotherapy agent containers, infectious waste containers, ignitable waste containers, hazardous P-list waste containers, hazardous U-list waste containers, toxic pharmaceutical waste containers, non-toxic pharmaceutical waste containers, chemotherapy sharps containers, corrosive waste containers, or reactive waste containers. Additional container types can also be used as desired. In one embodiment, the container types are pre-designated by the container provider. In other embodiments, the container types are assigned by the hospital so that the hospital can individually customize its waste sorting system. For example, some hospitals may desire to define their own waste categories in order to comply with internal goals, thus user-defined container types can also be provided.
[0073] In a preferred embodiment, a waste identifying mechanism is provided. In several embodiments, the waste identifying mechanism is configured to identify a particular item of waste. Identification is preferably accomplished prior to deposit into the appropriate container. Identification of the waste item can be accomplished by scanning a barcode, reading a label (e.g., using an optical scanner and Optical Character Recognition software), reading a Radio Frequency identification (RFID) tag, chemical sensors, spectroscopic analyzers, or by measuring or evaluating any other qualitative parameter of the waste item presented for identification. Alternatively still, an item of waste can be identified by user input of information such as a trade name, a generic name, a chemical name, National Drug Code (NDC) or other data associated with a particular item of waste. For example, a user can simply read a waste identifier from an item of medical waste and enter the identifier into the system via a keyboard, touch screen or other user input device.
[0074] In one embodiment, once an item of waste is identified, the sorting algorithm determines to which of a plurality of waste categories the item belongs. The station then indicates to the user which container is associated with that category. For example, in some embodiments the station indicates a correct container by opening a door providing access to the container. Alternatively, such an indication can be provided by illuminating a light or displaying a name or number of a container on a display device. In some embodiments, a waste sorting mechanism can carry out or instruct a user in delivery of the waste item to the appropriate disposable container.
[0075] In some embodiments, the waste sorting mechanism comprises a plurality of openings providing access to the plurality of containers. For example, each of the containers can be configured to interface with an automatically operable door or other means to present the container opening to the user. Some embodiments of such an interface are described in further detail below. Alternatively, the sorting machine can be configured to provide access to an appropriate container in other ways, such as by moving a container relative to the machine in order to present a container opening to a user. In further alternative embodiments, the sorting mechanism can include a series of lights or other indicators configured to inform a user of the correct container for a particular item of waste. Alternatively still, the sorting mechanism can include an apparatus configured to receive an item of waste from a user and physically convey the item to the appropriate disposable container.
[0076] In some embodiments, a single waste item may call for disposal in multiple containers. For example, a syringe might contain a quantity of a hazardous or controlled substance, which requires disposal in a first container. However, the syringe itself may require disposal in a second, separate container. In such embodiments, it is desirable for the system to determine an appropriate sequence for the disposal of the separate parts of a single item. In the event that a waste item contains information (such as a barcode or label) sufficient to inform the system of the need for a sequence of disposal steps, the system can determine the optimum sequence, and can then inform the user of the appropriate sequence. The system may inform a user of the appropriate sequence by sequentially opening appropriate doors and/or by displaying instructions on a display screen. In one embodiment, a means can be provided to determine whether an item of waste is empty or contains residual or bulk hazardous or non-hazardous contents.
[0077] Alternatively, it may be desirable for a user to determine the best sequence for disposal, in which case, the user may enter information into the system requesting a particular sequence. Additionally, it may also be desirable for the system to include “shortcut keys” in order to provide quick access to frequently-used containers, such as sharps containers. Such shortcut keys can be configured to quickly open a selected container.
[0078] In some embodiments, when a single waste item comprises a composite of elements falling into different waste categories, such as a syringe containing a controlled substance, which might, if disposed separately, be sorted into two different containers, the waste sorting system can indicate disposal of the composite waste item into the highest hazard level container. In this manner, when it is inefficient, ineffective or even dangerous to separate the single composite waste item into its individual components, hospitals can still achieve compliance by disposing of such hybrid or composite items into the most conservative hazard container. In some embodiments, the containers within a sorting station can be ranked in order from “least” to “most” hazardous in order to facilitate a determination of which container is the “most conservative” hazard container in a given station. A determination of whether a particular container type (and corresponding waste category or categories) is higher or lower on a hazardousness spectrum can be determined by a variety of suitable methods. In some cases, a hazardousness spectrum can be determined empirically, while in other embodiments, the varying degrees of hazardousness may be determined by comparing properties such as relative reactiveness, bioactivity, etc. of elements of a particular category.
[0079] In some embodiments, when a waste item is unrecognized by the identification means, the sorting system will indicate disposal to the highest hazard waste container. The system will notify the disposer that the waste item was unrecognized. In another embodiment, the sorting system may also notify a database or database personnel that the waste item is unrecognized, thus facilitating a database upgrade to include that waste item for future disposals.
[0080] In some embodiments of the invention, it may be advantageous to determine the quantity of waste that has already been deposited into one or more containers. In some embodiments, one or more sensors are used to quantitatively assess one or more parameters of the container and/or waste. These quantitative sensors include, but are not limited to, sensors that detect the weight, volume, density, and/or fill level of the waste in the container.
[0081] In one embodiment, one or more fill sensors are provided. A fill level sensor can be used to monitor a fill level of each of the disposable containers to determine when a particular container is full. Once a container is determined to be full, the sorting system can signal a user to replace the full container with a new empty container. Additionally, once a particular container is full, some embodiments of the system can be configured to determine the weight or volume of waste material within the full container. The system can also be configured to print a label to be affixed to the container. The label can include a variety of information relating to the disposal of the waste items, the quantity, weight or volume of the items contained therein, a waste category name or code, etc.
[0082] In some embodiments, quantitative sensors are not used. Instead, in one embodiment, the quantity of waste is determined by direct visualization of the waste in a container. Transparent or translucent containers are provided to facilitate visualization in some embodiments. In several embodiments, the containers are opaque, but provide a section or “view-strip” of translucent or transparent material to permit visualization. In one embodiment, one or more sensors are provided in conjunction with means to directly visualize waste quantity. In one embodiment, means for detecting a quantity of waste are not needed because the containers are replaced at regularly scheduled intervals, as determined by a waste transport company, a disposal company or hospital staff and independent of how much waste is in any given container.
[0083] In some embodiments, when a new container is placed in a sorting and disposal station, the system can be configured to identify the new container according to the type of waste the container it is permitted to hold. In some embodiments, a waste sorting and disposal station can be configured to recognize containers in a static mode in which each container position within the station/machine is associated with a specific container type. Upon insertion of a new container into the station, the system can recognize the type of container and can determine whether the new container is the correct type for the position in which it was placed. Thus, a system of this type can insure that a consistent arrangement of container types is maintained.
[0084] Alternatively, and more preferably, a sorting and disposal station is configured to recognize container types in a dynamic mode in which the machine is able to recognize and adapt to changing container arrangements. Thus, according to this embodiment, each container position/compartment in a station will recognize and accept any new container regardless of the container type, and the software will adapt a sorting routine to account for the new configuration. In some cases, it may be desirable for a single station to have multiple containers of a single type. For example, an oncology department may desire several chemotherapy containers and no hazardous pharmaceutical containers, while an area of the hospital that does not use chemotherapeutic drugs may want several sharps containers and no chemotherapy containers. This allows for substantial flexibility and customizability in system set up. In further embodiments, a sorting and disposal station can exhibit aspects of both static and dynamic systems, such as by allowing any type of container in any container position, while requiring a minimum number of containers of a particular type.
[0000] Network-Implemented System
[0085] In some embodiments, a waste sorting and disposal system can be configured on a hospital-wide level by providing a plurality of cooperating sorting and disposal stations throughout the hospital. The system can include a plurality of individual sorting and disposal stations in a variety of types, arrangements, sizes, functionalities, etc.
[0086] FIG. 1 illustrates an exemplary embodiment of a centralized waste sorting and disposal network. As shown, a centralized network 50 can include a main central unit 54 provided in electronic communication with a plurality of smaller “satellite” units 60 throughout a facility. In such a centralized network, the main unit 54 can include a server containing the classification database 56 and any other information to be shared with the satellite units 60 . As information is needed by a satellite unit 60 , it can query the database via the network in order to obtain that information. Alternatively, or in addition, the main unit 54 can be configured to push updates to the satellite units at regular intervals, or as new information becomes available. In some embodiments, the main unit 54 can also act as a central hub for various communications, tracking, maintenance and other system functions.
[0087] FIG. 2 illustrates an embodiment of a de-centralized medical waste sorting and disposal system. The network 64 of FIG. 2 is substantially decentralized and comprises a plurality of sorting and disposal stations 60 which can communicate with one another according to any suitable method. For example, in a decentralized network, each of the individual units may locally store a copy of the classification database. In order to keep the classification database updated, the individual units can share information with one another according to any of a variety of peer-to-peer network protocols. The individual stations can also share other information with one another as will be further described below.
[0088] In either case (centralized or decentralized network), the network elements can be configured to communicate with one another via any suitable wired and/or wireless network communication protocol. Many hospitals already have existing wired and/or wireless networks connecting computers and communications devices throughout the facility. Thus, in some embodiments, a networked medical waste sorting and disposal system can be configured as an add-on to an existing network. Alternatively, a networked medical waste sorting and disposal system can be configured as an independent network. Additionally, the main unit (if present) and/or the satellite unit(s) can further be connected to external networks (e.g., the internet) via wireless or wired connections as desired.
[0089] In some embodiments, it may be desirable for one sorting and disposal station to have access to information about one or all of the other stations in the network. For instance, it may be desirable for any one station to determine an arrangement of containers in one or more nearby stations. For example, if a clinician presents an item of waste to a station which does not presently have a container suitable for disposal of the presented item, that station can direct the clinician to the nearest station that does have an appropriate container installed. In further embodiments, a log of such re-directions can be kept in order to increase efficiency by arranging the sorting and disposal stations to include the most frequently used containers for a given location.
[0090] Some embodiments of a waste sorting and disposal system are configured to communicate information directly to a technician, maintenance person, clinician or other person. For example, the system can be configured to alert a maintenance person when a container is full by sending an alert signal to a pager, cell phone, PDA, computer terminal, or any other suitable device. The maintenance person can then remove the full container and replace it with an empty container (of the same or a different type).
[0000] Individual Sorting/Disposal Stations
[0091] A medical waste sorting and disposal station can take a variety of forms depending on the specific needs of a given clinic, hospital, department, clinician, etc. For example, some embodiments of sorting and disposal stations 60 are illustrated in FIGS. 3-12 . For example, a station can be provided in a wall-mounted unit 60 a (e.g., see FIG. 3 ), in a floor-standing unit 60 b ( FIG. 4 ), on a wheeled cart 60 c ( FIGS. 5 and 6 ), attached to a patient bed, attached to an IV pole, attached to an existing wheeled medications cart 60 d ( FIGS. 7-9 ), or any of a variety of other shapes, forms and mounting locations.
[0092] The embodiment of FIGS. 5 and 6 also includes a display device 70 , a weight scale 72 , a scanner 74 for identifying waste items and a plurality of apertures 78 configured to reveal openings to respective containers 80 .
[0093] With reference to FIGS. 7-9 , some embodiments of a station can comprise a movable lid 82 with a single aperture 84 . The lid 82 can be substantially flexible such that it can be driven to translate above the containers in order to selectively provide access to any one of the containers below the lid 82 .
[0094] In some embodiments, the sorting machine can be configured to provide access to an appropriate container in other ways, such as by tilting, raising, lowering, pivoting, translating or otherwise moving a container relative to the machine in order to present the container opening to a user.
[0095] FIG. 10 illustrates an embodiment in which a sorting station comprises a series of hinged sleeves 86 configured to pivot relative to a fixed portion of the sorting station. Each sleeve 86 is generally configured to temporarily house a disposable container 80 . The station 60 e comprises a series of actuators configured to pivot each sleeve 86 and its associated container 80 outwards, thereby exposing the container opening 88 . In one embodiment, an actuator 90 can be located adjacent an upper portion of a container 80 and can be configured to push the upper portion of the container outwards from the station. Alternatively the sleeve 86 can be biased outwards by a spring or simply by gravity, and an upper actuator can be configured to release the sleeve/container to allow it to pivot outwards to open. The upper actuator can then pull inwards to return the container/sleeve to a closed position.
[0096] Alternatively or in addition, a lower actuator 92 can be provided adjacent a bottom portion of the container/sleeve combination. In one embodiment, a lower actuator 92 can comprise a drive axle 94 rigidly mounted to the sleeve 86 . The axle 94 can be driven by a motor or other mechanism in order to pivot the sleeve 86 inwards and outwards. A container 80 can be inserted into the sleeve 86 and pivoted back so that a fixed portion of the station 60 e covers the container opening 88 . During use, the actuator 90 or 92 causes the sleeve 86 to pivot outward from the station 60 e, thereby exposing the container opening for use. The container 80 can be removed by sliding it out of the sleeve 86 . In an alternative embodiment, the above system can be provided without a sleeve 86 by incorporating an actuator and a pivot point into the container itself In further alternative embodiments, other actuators, drive mechanisms, etc can be used in order to selectively provide access to a container opening.
[0097] In another embodiment, the station can be configured to house each of the containers in a sliding drawer. The drawers can include actuators configured to move the drawer outwards until an opening is exposed. The containers can then be easily removed once they are full.
[0098] FIGS. 11 and 12 illustrate another embodiment of a waste sorting and disposal station 60 f in the form of a convertible rolling cart. In a first orientation, illustrated in FIG. 11 , the station 60 f is a two-sided rolling cart. The station 60 f of this embodiment can be provided with a hinge 96 configured to allow the two sides 98 a, 98 b of the cart 60 f to unfold into a one-sided arrangement. In this second configuration (shown in FIG. 12 ), the station can be mounted or placed against a wall.
[0099] In some embodiments, a sorting and disposal station 60 can include a scale configured to determine a weight of a full container. Thus, a scale 72 can be provided on an upper or other accessible portion of the station. Alternatively, the station can include a scale (e.g., a load cell) to continuously or repeatedly weigh each container within the station. Such information can be useful in creating a manifest for the containers before transportation of the containers to an appropriate disposal facility. Additionally, or alternatively, a station can include a fill level sensor for continuously or intermittently determining a fill level of a container. Embodiments of a fill-level sensor are described in further detail below.
[0000] Disposable Containers
[0100] In some embodiments, the disposable containers are generally designed to be low cost, yet include features that provide a functional interface with mechanisms in a sorting station to perform several desired functions. For example, in some embodiments, each container includes a door or lid which can be opened and closed automatically in order to allow or prevent access to a particular container at a particular time. Additionally, the containers can be configured to interface with sensors for determining a quantity of contents within the container, and/or sensors for determining a type of container.
[0101] In some embodiments, the containers 80 are blow molded (or otherwise formed) from polypropylene, high molecular weight polyethylene, polyvinylchloride or any other suitable plastic or other material as desired. In some embodiments, the containers 80 have substantially frosted or translucent side walls. The containers will typically be sized to have an internal volume of anywhere from 1 to 20 gallons, however greater or smaller volumes can also be used as desired. For example, in some particular embodiments, containers can be provided in 1-gallon, 3-gallon and 8-gallon sizes.
[0102] The shape of the containers can vary widely. In some preferred embodiments, the containers include a lifting handle, a primary opening which can be automatically and/or manually closed or sealed, and a bottom surface configured to allow the container to stand upright. Additionally, the disposable containers can also include features such as an automatically-openable door or lid, a manually closable lid, features for accurately locating the container in a container compartment of a station, a viewing window for visually verifying a fill level, and/or identification information for informing a user of a container's contents (or intended contents).
[0103] The containers can be provided with an opening 88 having a variety of shapes and/or features. For example, in one embodiment, the opening 88 is substantially circular and has a minimum internal diameter of at least about three inches (˜76 mm). In other embodiments, the opening 88 can be substantially elliptical, rectangular, polygonal or otherwise shaped, and can be any suitable size, including sizes smaller than three inches in diameter. The particular type or types of waste to be deposited in a particular container can be a significant factor that can be used in determining a suitable size and/or shape of a container opening. In general, the container opening should be sized to easily accept the largest waste item that is expected to be deposited in the container. For example, some containers might receive full or partially full liter-sized IV bags, gallon-sized biohazard bags or other large items. It is generally desirable that the container opening be configured to accept these large items easily and without tearing the bags or otherwise damaging or causing spillage of a waste item. The skilled artisan will recognize that other factors may also affect a choice of container opening size or shape.
[0104] In some embodiments, disposable containers are provided in a plurality of types, each type corresponding to a respective waste category or waste classification. In order to allow clinicians, maintenance people, and any other persons who may handle the containers to quickly and easily differentiate containers of various types, the containers can be color-coded to correspond with a particular type or category of waste. In some embodiments, a color-coding scheme can be selected to match industry standards for various types of medical waste. Red, for example, typically signifies infectious waste, while yellow typically signifies chemo therapy drugs. Color-coded containers can advantageously simplify the tasks associated with manual transportation and processing of the containers, and can aid in insuring that such tasks will be handled correctly for each waste stream.
[0105] Alternatively, such visual verification of a container's type can be provided by any other suitable method. For example, the various container types can be indicated by labels bearing numeric, alphanumeric, graphical or symbolic information. Such labels can include printed stick-on labels or various features molded or formed directly into portions of the containers themselves. If desired, such type-identification features can be provided in addition to color-coding of the containers in order to further simplify identification of a container's type. Providing simple visual verification of a given container's type advantageously simplifies and facilitates handling of medical waste materials throughout many aspects of collection and disposal.
[0106] In some embodiments, the containers can be configured in such a way that a sorting and disposal station can automatically identify a type of container. Such automation allows a station/machine to detect the mix and arrangement of container types in the station at any given time. In some embodiments, each container includes an identification key that can be read by corresponding structures in a sorting station. The key generally allows the sorting station to automatically identify the type of each container occupying a compartment or container position within the station. As discussed above, the station can be configured to identify container types in either a static or dynamic mode depending on a desired degree of flexibility for a given station.
[0107] Identification keys may be physical features such as fingers molded into or attached to each container. Alternatively, identification keys can be holes, notches, or grooves molded or cut into a portion of each container. In some embodiments, identification keys include optically-readable features such as holes, dark or light colored dots, text, symbols, graphics, etc. A physical key may be configured to be read by mechanical or optical switches associated with each compartment or container position within the station. For example, FIG. 13 illustrates an embodiment of a container 80 with an identification key 104 made up of a series of holes 110 in a flange 112 extending from an upper portion of the container 80 . The holes 110 of FIG. 13 can be detected by a plurality of optical switches 138 mounted to a portion of the station adjacent a container position. Thus the various container types can be identified by providing holes (or other features) in varying combinations and positions.
[0108] Alternatively, a key may be an optical mark, such as a bar code, that can be interpreted by a sensor such as a bar code reader. Alternatively still, the key may be a radio frequency identification (RFID) tag that can be read by a transponder associated with each compartment. In still further embodiments, container identification keys can comprise microchips, magnetic strips, or other electronic media that can be read by a waste sorting and disposal station into which the container is placed. In one alternative embodiment, a polychromatic sensitive optical sensor can be provided to directly determine a color of a container.
[0109] As discussed above, some embodiments of a disposable container are provided with automatically operable doors. In such embodiments, a container can be closed by default to prevent insertion of items into an incorrect container. Then, once an item is scanned or otherwise identified, the station can open the appropriate container or otherwise signify the single correct container to receive that particular waste item.
[0110] FIGS. 14-17 illustrate embodiments of containers comprising integrally-formed automatically operable doors and corresponding structures in a sorting station. The illustrated structures are generally configured to provide an automated interface between a container 80 and portions of a sorting and disposal station in order to allow the station to automatically recognize and operate a container. According to these illustrated embodiments, each compartment includes an actuator mechanism configured to automatically and selectively open and close the corresponding container 80 . The selective opening and closing of each container may be accomplished via interaction of structures on both the disposable container and the station, and can ultimately be controlled by a computer system within the sorting and disposal station.
[0111] In some embodiments, a container may include a movable lid molded or otherwise joined to the container opening. The lid can generally be configured to pivot, slide, hinge or rotate relative to a container in order to reveal or cover the container opening. In some embodiments, the lid is configured to mate with a mechanical actuator in the station upon installation of the container in a given container compartment. The actuator can be configured to cause the lid to open and close by translating, rotating or pivoting the lid. The actuator and lid can be further configured to separate from one another when the container is removed from the station.
[0112] FIG. 13 illustrates one embodiment of an interface between a container 80 and portions of a sorting station. In the illustrated embodiment, the container 80 comprises a gate 116 covering an opening 88 and configured to slide in tracks 118 between an open position and a closed position. The gate 116 can include a latch 120 configured to lock the container opening when the gate 116 is completely closed. When a new container 80 is inserted into a station, a drive pin 122 on the gate control arm 124 is engaged by the gate 116 of the container. The control arm 124 is configured to open and close the gate 116 . The gate control arm 124 can be coupled to a drive motor 128 via a transmission element such as a disc 132 or a similarly functioning arm. If desired, a position switch 134 can also be provided on the disc 132 , control arm 124 , gate 116 or other component in order to detect a position of the gate 116 . In the illustrated embodiment, the position switch 134 is an optical switch configured to detect one or more holes 136 in the disc 132 . Additionally, the sorting station can include a plurality of optical switches 138 for detecting the presence of a container and/or the type of container 80 inserted into the sorting station. The embodiment of FIG. 14 replaces the gate control arm 124 of FIG. 13 with a slot 140 in the gate 116 in order to convert the rotational motion of the pin 142 extending from the disc 132 into linear motion of the gate 116 .
[0113] In alternative embodiments, other configurations of automatically openable doors/gates can be provided For example, FIG. 15 illustrates an alternative embodiment of a container comprising a sectioned door 150 configured to slide along tracks 152 extending from the exterior surface of the container 80 . The slidable lids of the above embodiments can be provided with a latch (such as that shown in FIGS. 13 and 14 ) which can be automatically engaged in order to lock the container once a sorting station determines the container is full. The embodiment illustrated in FIG. 16 can include a slidable door 116 driven by a rack and pinion drive mechanism 156 . Alternatively, the drive mechanism 156 of FIG. 16 can comprise a driven friction wheel configured to engage a portion of the slidable lid 116 . A similar pinion or friction wheel drive system can be used to automatically operate the sectioned door 150 of the embodiment shown in FIG. 15 . FIG. 17 illustrates an embodiment of a container 80 with a lid 158 configured to open by pivoting relative to the container 80 . In further alternative embodiments, a door can be opened or closed by any of a variety of other mechanisms. For example, worm screws, pneumatic pistons, hydraulic pistons, solenoids, or any other motion-transferring mechanism can be used to selectively open and close a container door.
[0114] In some embodiments it may also be desirable to provide an outer lid configured to seal a container opening once the container is full. The outer lid is preferably configured to attach to the container sufficiently securely to prevent spillage or tampering. An outer seal also shields users from contaminants that may have come in contact with the container top area during use. For example, in some embodiments a flexible lid can be configured to seal over a top of the automatically actuated door by frictionally engaging a lip, groove, or other structure in a manner similar to many flexible lids used in food storage containers. In alternative embodiments, outer seals can be provided in the form of a bag or shrink-wrap material that surrounds a substantial portion of a container's exterior.
[0115] In some embodiments, it may be desirable to provide a container configured to render waste items non-recoverable by providing a substance within an “empty” container that can react chemically with waste items. In another embodiment, a solidifying agent can be provided within a container in order to solidify non-hazardous pharmaceuticals allowing for their disposal in a landfill. In some embodiments, such solidifying agents can include materials capable of absorbing a quantity of a liquid non-hazardous pharmaceutical material. For example, such absorbent materials can include ceramic materials, sponge materials or other porous materials. Alternatively, such solidification may involve a chemical reaction between the waste material and a substance provided within the container.
[0000] Fill-Level Detection System
[0116] In some embodiments, it is desirable to measure a fill level of waste within a container throughout the sorting and filling process. In some embodiments, such fill level sensing can be performed by measuring a weight of a container, such as by using a load cell, balance, or other weight measurement device. In further embodiments, float systems can be adapted for use in determining a level of a waste material in a waste sorting system. In some cases, it is also desirable to perform such fill level measurements without the sensor physically contacting the container or the container contents.
[0117] In some embodiments, a piezo transducer can be used to determine a volume of air remaining in a container by conducting a frequency sweep of the transducer to determine the resonance of the air in the container. Once the volume of air in the container is known, the air volume can be subtracted from the known total container volume to obtain the volume occupied by the container contents. In another alternative embodiment, a distance-measuring sensor (such as SONAR, RADAR or optical distance-measuring sensors) can be located above and directed through the opening of the container in order to determine a “height” of the container contents. In another embodiment, a sensor can be provided for determining whether a container includes any waste at all. Such a “waste presence” sensor can be used in combination with a timer to determine a replacement schedule for a particular container based on a maximum acceptable dwell time for a particular waste item in a container. Still other embodiments may use optical sensors to measure a fill level of a container.
[0118] FIGS. 18-19 illustrate one embodiment of a level sensor which can be used to automatically determine a fill level of a container using an optical method. As shown in the schematic illustration of FIG. 18 , one embodiment of a fill level sensing system comprises a light source 230 and a light detector 232 positioned on opposite sides of a disposable container 80 . In alternative embodiments, the light detector 232 need not be located immediately opposite the light source, for example, in some embodiments the detector can be located on a wall adjacent to the source 230 . The sensor system of FIGS. 18 and 19 generally operates on the principle that an “empty” container will permit more light to pass from the source, through the container, and to the sensor than will a “full” container. This is simply due to the fact that the contents of the container 80 will absorb and/or reflect a substantial portion of the light which enters the container from a light source.
[0119] As used herein, the terms “empty” and “full” shall be given their ordinary meaning and shall be used to define relative amounts of debris, or other matter, in a container. For example, in certain embodiments, the sensor may indicate that the container is ready to be emptied or discarded, not because it is completely saturated, but because it has reached the desired point of fill or saturation. In some situations, it may be desirous to empty or remove a container when anywhere from about 1% to about 100%, often from about 25% to about 100% of that container contains waste material. In other situations, it may be desirable to remove a container when about 50% to about 95% of its volume is occupied by waste material.
[0120] In some other embodiments, a parameter other than weight or filled volume may be used to determine when a container is “full.” For example, in one embodiment, a sensor to detect radioactivity is used to determine the amount of radioisotope in a container or receptacle. The radioactivity sensor may used in connection with a fill sensor, or it may be used alone. Thus, in some embodiments, a container may be emptied, discarded, or replaced based on a certain amount of radioactivity, rather than (or in addition to) the surface area, volume, weight, density and/or another parameter of the material in that container.
[0121] In yet another embodiment, a sorting and disposal system can be provided without any automatic level detection apparatus. For example, in such an embodiment, the containers can be configured to allow a clinician, maintenance person, or other user to visually verify a fill level of the container. In such embodiments, the containers can be made of a substantially transparent or translucent material. Alternatively, the containers may be substantially opaque but can include a transparent viewing window to allow visual verification of a fill level. Such viewing windows could extend substantially an entire height of the container, or could extend only a height of a desired portion of the container.
[0122] In some embodiments, the source 230 and detector 232 are located along a “fill line” which generally defines a “fill plane.” The fill plane 240 is generally the level within the container 80 which a processor 242 defines as “full.” In some embodiments, the actual free surface of contents within a container may not necessarily be planar. In such embodiments, the “fill plane” used by the processor and fill level sensing system is simply an average height of the material.
[0123] In the embodiment illustrated in FIG. 18 , a light source 230 is located at a “front” of the container and a detector 232 is located at a “rear” of the container. In alternative embodiments, the positions of the light source 230 and detector 232 can be reversed, or positioned at any other position around the container 80 . In still further embodiments, multiple sources and/or detectors can also be used as desired.
[0124] As discussed above, the containers 80 are typically made of a translucent material which allows at least some amount of light to pass through its walls. The embodiments of a fill level sensor illustrated in FIGS. 18 and 19 are particularly advantageous when used to measure a fill level of a container with translucent sidewalls. However, the skilled artisan will recognize that certain advantages of the embodiments described herein may be advantageously applied to systems using containers having transparent sidewalls or containers with transparent windows in otherwise relatively opaque sidewalls. As used herein, the term “translucent” is used in its ordinary sense and refers without limitation to a material which allows the diffuse transmission of light when illuminated, while remaining substantially non-transparent when not illuminated.
[0125] The light source can comprise any suitable source of light such as incandescent bulbs, white or colored LED's, or other sources. In some embodiments, the light source 230 is located such that it is vertically centered on a desired “fill line” 240 of the container. The light source can be laterally centered relative to the container, or can comprise a width that is about as wide as the container 80 . In still further embodiments, a plurality of light sources can be used to illuminate a container from multiple points.
[0126] As illustrated in FIG. 19 , the light detector 232 can comprise an array of photo detectors 236 such as cadmium sulfide photo detectors or photodiodes. In the illustrated embodiment, the array of photo detectors 236 comprises three rows 244 , 246 and 248 of detectors 236 . The upper row 244 contains a single detector 236 while the middle 246 and lower 248 rows contain a plurality of detectors 236 (three in the illustrated embodiment). In alternative embodiments, the upper row 244 can be provided with additional detectors which equal or exceed the number of detectors in the other rows. Similarly, the middle 246 and lower 248 rows can include fewer or more than three detectors as desired. The number of detectors in each row will typically be determined by the algorithm used to determine the fill level of the container and/or the degree of accuracy desired. In some embodiments, it may also be desirable to provide more than three rows of detectors. For example, in some embodiments, a fill level detection system can be provided with four, five or more rows of detectors.
[0127] In some embodiments, the middle row of detectors is positioned to lie just above the fill line 240 of the container 80 , and the lower row 248 of detectors 236 is positioned just below the fill line 240 . The upper row 244 of detectors 236 can be located substantially above the fill line, and can be used to calibrate the detectors middle 246 and lower 248 rows as will be described in further detail below.
[0128] In some embodiments, the upper and middle rows can be spaced by a distance 250 of between about ½ and about 2 inches, in other embodiments the upper and middle rows can be spaced by a distance 250 of between about 1 inch and about 1½ inches, and in one particular embodiment, the upper and middle rows are spaced by a distance 250 of about 1¼ inches. Similarly, the middle and lower rows can be spaced by a distance 252 of between about ½″ and about 2 inches, in other embodiments, the middle and lower rows can be spaced by a distance 252 of between about 1 inch and about 1½ inches, and in one particular embodiment, the middle and lower rows are spaced by a distance 252 of about 1¼ inches. In some embodiments, the detectors 236 of the middle 246 and lower 248 rows are spaced horizontally by a distance 2254 of between about ½ inch and about 3 inches, in other embodiments, the detectors 236 of the middle 246 and lower 248 rows are spaced horizontally by a distance 254 of between about 1 inch and about 2 inches, and in one particular embodiment by a horizontal distance 254 of about 1½ inches. In some embodiments, the sensors are evenly spaced, while in other embodiments, the sensors of the middle row are horizontally spaced differently than the sensors of the lower row. In further alternative embodiments, the spacing of the detectors 236 can be determined by factors such as the size of the container or the material to be placed within the container.
[0129] In operation, the individual photo detectors 236 pick up light transmitted through the container and output corresponding signals to a processor 242 . On one hand, the light intensity arriving at the detectors 236 depends on the fill level of the container 80 . In addition, a number of secondary factors also effect the light intensity reaching the detectors 236 . These include the strength of the light source 230 , the color and opacity of the container 80 , the amount of ambient light, and other factors such as dust in the air. The light intensity at the top detector row 2244 is almost completely governed by these secondary factors, since it is located well above the fill line 240 . By contrast, the light intensity arriving at the middle 246 and lower 248 detector rows will be effected more by the fill level of the container contents as the container 80 becomes more full (e.g., as the fill level approaches the fill line).
[0130] When the container 80 is empty and the overall light intensity is greatest, a baseline reading is recorded and calibration coefficients are generated for each of the detectors 236 and detector rows 244 , 246 , 248 . As the container fills, the received light reaching the detectors decreases slightly as material in the container blocks a portion of the diffused light transmitted through the container 80 . During this phase, the top detector reading is used to compensate the readings of the middle and lower detector rows accordingly. When the container contents reaches the fill line, the bottom row of detectors will be blocked by the container contents, while the middle 246 and upper 248 detector rows remain unobstructed. This results in a substantial drop in the light intensity reaching the bottom row 248 of detectors, and correspondingly, a substantial difference in signal strength between the middle 246 and lower 248 detector rows. When this signal difference reaches a pre-determined threshold level, the processor determines that the container is “full.”
[0131] In some embodiments, the items being deposited into a container may be stacked unevenly or oddly oriented within a container so that the contents of a container vary from a neat horizontal fill level. For example, some large items, such as syringes or other contaminated medical devices, may stack oddly within a container, thereby creating voids of unfilled space in a central portion of a container, above which waste items may be stacked. Such variations in filling can lead to lead to measurement errors. Thus, in some embodiments, a level sensing system can be provided with error processing capabilities to account for variations in orientation and/or uneven loading of a container.
[0132] For example, in some embodiments, the signals from the plurality of detectors in each row are averaged to provide a consensus value for the respective detector row. This advantageously allows the processor to determine an average fill level in the event of an uneven fill surface. For example, in an idealized case, a container filled with a plurality of spherical particles through a hole in the top center of a regularly-shaped container will typically have a free surface in a shape of a cone with a peak at the center, and dropping off evenly in each direction. In such a case, the center detector of the lower row 248 will typically receive a lower light intensity than the detectors on either side. Thus, by using the data from all of the detectors in a horizontal row, a processor can calculate an approximate average fill level in order to prevent over-filling of the container.
[0133] These or other error-processing techniques can also be used to compensate for manufacturing defects in a container that might result in erroneous results. For example, if a plastic container wall comprises an air bubble or a dark spot in a region adjacent one or more of the detectors, these abnormalities could cause erroneous readings by those detectors. To compensate for this, a system may give less weight (or no weight at all) to signals from detectors that are out of a statistically expected range of variation from the remaining detectors. By taking an average signal across all detectors in various combinations and/or by assigning varying weights to individual detectors, a control algorithm can teach itself to recognize and adapt to such error-causing situations in order to obtain consistent readings.
[0134] In some embodiments, the functionality of a fill level sensing system employing a light source and a plurality of optical detectors can advantageously be enhanced by containers with “frosted” or translucent walls. Another advantage of certain embodiments of a level sensing system as described herein is that such systems can be polychromatic sensitive (i.e. configured to sense light of various colors with consistent accuracy). Thus, in addition to measuring a fill level of a container, the above-described sensors can be configured to determine a color of a container (each container color being associated with a particular container type as discussed above). In some embodiments, these and other advantages are achieved through the use of cadmium sulfide photosensitive cells. In alternative embodiments, optical level sensors can be constructed using other optical detectors, including other photoconductive cells, photo diodes, or other sensors capable of detecting light in the visible or infrared spectrum.
[0135] In some embodiments, each one of a plurality of fill-level sensors is controlled by a single processor in a waste sorting system. In one embodiment, a plurality of photo detector arrays can be connected to a single multi-channel bus, and a plurality of light sources can be controlled by a processor. In this embodiment, the processor can illuminate a single container at a time. Thus, the detectors behind each of the “dark” containers would be at high impedance, and would therefore be out of the circuit.
[0136] In some embodiments, a fill level sensing system employing optical sources and detectors can include an additional photo detector that is generally configured to measure changes in “ambient” light within the system in order to appropriately adjust the readings from the detector arrays measuring fill level. An ambient light detector can comprise a single optical detector, or a plurality of detectors in a circuit. In one such embodiment, an additional ambient light detector is provided within a waste sorting system in a location selected to measure any light entering the system from the exterior of the sorting system. For example, the ambient light detector can be located adjacent a container-replacement door or any other portion of the system that is open to external light.
[0137] FIG. 22A illustrates one embodiment of a circuit schematic which can be used in building an optical fill level sensor such as that illustrated in FIGS. 18 and 19 . The skilled artisan will recognize that this is merely one exemplary schematic, and that alternative embodiments of the system of FIGS. 18 and 19 can be built using any appropriate components.
[0138] FIGS. 20-22 are flow charts illustrating embodiments of software algorithms used by a level detector for use in a sorting system. FIG. 20 is a flow chart illustrating an overview of a level testing algorithm. When the system determines that a new container has been inserted, the level sensor establishes new baseline values for the detectors in order to define the “empty” state. The level sensing system then reads values of the detectors 236 and inputs the detector values to an inference engine ( FIGS. 21 and 22 ).
[0139] The inference engine can use a “fuzzy logic” method similar to the Sugeno method. In one embodiment, the inference engine uses a table of empirically-determined data to establish rule weights. The inference engine can also use multiple grouping of detectors in addition to individual detector levels to calculate a final fill level of the container. In some embodiments, the empirically-determined lookup table can be developed by performing various calibration experiments using an optical level sensing system to measure containers at known fill levels. In addition to any controlled experiments, the lookup table can be supplemented by analysis of information it receives during use in measuring fill levels of new containers. For example, as optical anomalies are detected and accounted for, the software can adapt to correct for them.
[0140] FIGS. 21 and 22 are flow charts illustrating one embodiment of an inference engine. In order to avoid misleading readings during filling, the system can be configured to determine when the detectors are at a steady state (e.g., when the movement of waste within the container drops below a threshold level). This is particularly helpful in embodiments in which a waste material is a liquid, and thus may continue moving for a period of time.
[0141] Once steady state is reached, the inference engine compares the values of the detector readings and ultimately derives a final fill value which can be stored and/or output to a user-readable device such as a liquid crystal display. In alternative embodiments, an output of the system can include other visible, audible or tactile alerts, such as LEDs, buzzers, bells, vibrators, etc. In some embodiments, an output signal is used to notify the user that a particular container is ready to be emptied, discarded, replaced etc. In an alternative embodiment, an output signal is provided substantially continuously or at various intervals, so that the user can determine or monitor the amount of material in a given container at any given time. For example, in some embodiments, the fill-level of a container can be measured at regular intervals, such as every ten minutes, every hour, every two hours, every six hours, every 12 hours, or every 24 hours. In still further embodiments, the system can comprise a sensor (such as an optical sensor) to determine when an item is deposited into a container. Then a fill-level of the container can be measured after each item is deposited in the container.
[0142] FIG. 23 illustrates an alternative embodiment of a video fill level sensing system. The embodiment of FIG. 23 employs a camera 270 to continuously detect an intensity of light exiting the container from the source. In the illustrated embodiment, a light source 270 is positioned to illuminate the container 80 , and a curved mirror 274 and pinhole video camera are located adjacent another side of the container 80 . The system can also include a software-based processor 276 and other electronic hardware. In the illustrated embodiment, the light source 270 is located adjacent one vertical side of the container 80 and the camera and mirror are positioned on the opposite side of the container. In alternative embodiments, the light source 270 and camera/mirror assembly can be located on adjacent sides of the container 80 . Alternatively still, the light source 270 can be located above the container such that light is directed downward into the container, thereby allowing the waste to absorb as well as reflectively diffuse the light source onto the walls of the container 80 .
[0143] In some embodiments, the camera 270 is directed at the mirror 274 to detect light emitted from the container 80 and gathered by the mirror 274 . The curved mirror 274 provides a linearization of scanline width by distorting the optics of the camera. In one embodiment, the camera 270 is a pinhole camera, which is selected due to the depth of field this type of lens provides. In one embodiment, the curved mirror 274 has a shape substantially similar to a shoehorn, e.g., it is curved about two perpendicular axes (e.g., longitudinal and transverse axes). Alternative mirror configurations can also be used as desired. The particular curvature of the mirror 274 is determined empirically depending on the width of scanline needed and the height of the measured area (e.g., the height of the container wall). Variation in the curvature of the mirror along its length allows the scanline to be optimized in order to emphasize areas of higher interest and to de-emphasize lower interest areas. The mirror can be convexly curved at the height of higher interest areas, and concavely curved to de-emphasize lower interest areas.
[0144] In some alternative embodiments, the light source can include bands of varying color or intensity along the height of the container in order to provide emphasis to portions of the container, or to provide “watermark” levels that can be measured against. In some embodiments, the software can be configured to interpret information received from the camera to learn about points of interest in order to further optimize a measurement algorithm. For example, rather than programming an algorithm to anticipate areas of higher or lower interest, the algorithm can be configured to recognize variations in light intensity during calibration in order to detect such areas of higher or lower interest.
[0145] The processor and its support hardware provide the sampling of multiple luminance intensities along the wall of the container 80 adjacent the mirror 274 . The analog video signal is amplified and ground-referenced by the video amplifier. This amplified signal is scanned for a selected scanline to digitize for quantifying its luminance value. The amplified video is also applied to the Sync Separator module, which produces timing pulses for the scanline selector module. The processor receives the scanline data from the scanline selector, digitizer and sync separator. The video level sensor can determine a current fill level of the waste in the container 80 using a similar software method to that described above with reference to FIGS. 18 and 19 . FIG. 23A illustrates one embodiment of a circuit schematic which can be used in building a video fill level sensor such as that illustrated in FIG. 23 . The skilled artisan will recognize, however, that this is merely one exemplary embodiment. In alternative embodiments, the system of FIG. 23 can be built using any appropriate components.
[0146] Many of the above embodiments of fill level sensors were described with reference to a single disposable container. In some alternative embodiments, it may be desirable to provide a single fill level detection system configured to selectively measure a fill level of any one of a plurality of containers. For example, in one embodiment, a light source may be provided on a first side of a plurality of containers, and a light detector can be movable into a position opposite the light source of the containers. In one embodiment, this may take the form of a circular arrangement of containers in which a light detector is located at a center of a circular arrangement of containers. One or more light sources can be positioned on an outer portion of the circular arrangement such that the light source and/or the light detector is capable of measuring a fill level of each one of the plurality of containers around the circle.
[0147] In some embodiments, the sorting system can also include a weight scale (such as a load cell, pressure transducer, mechanical scale or other device) configured to weigh either a single spent drug, container or individual segregated spent drugs. In one embodiment, the information from the scale can be sent to a printer providing a means for printing a manifest for the container. Additionally, such information could be combined with other information available to a clinician in order to determine a quantity of a drug or substance that has been used or consumed. Many hospitals are automating the dispensing of drugs. The automation is usually embodied in a piece of equipment that a doctor or nurse accesses with a patient and clinician code and the correct amount of drug is dispensed. The automation provides pharmacists, nurses, doctors and administrators with information from a database on what drugs are dispensed and to which patient. These systems can typically indicate how much of a drug was administered, but entering this information typically requires a clinician to return to the dispenser (which may be inconvenient, and thus not done regularly). This information can be quite useful because it will demonstrate any inefficiencies or mistakes in administrating the drugs as well as point out any theft of drugs. In some embodiments, a sorting and disposal system can be configured to track dispensing information because at the point of throwing the spent drug away, they are automatically providing information to a central database.
[0000] Sorting Algorithm
[0148] Embodiments of a pharmaceutical waste sorting and disposal system will generally employ a waste sorting algorithm to assign each item of waste to a particular waste category and correspondingly to a particular waste container. A waste sorting algorithm can take a variety of forms, and can include a range of functionalities.
[0149] In some embodiments, as discussed above, determination of the waste categories themselves can depend on a number of factors, including RCRA hazardous waste definitions, state and federal EPA regulations, OSHA regulations, and any institution-specific regulations. For example, RCRA definitions generally include a P list, a U list and four characteristics of hazardous waste: ignitability, corrosivity, toxicity and reactivity. Materials exhibiting each of these characteristics typically call for different handling, treatment and/or disposal. Thus, in some cases waste categories can be defined based on groups of materials that require the same or similar handling, treatment, or disposal. However, in some cases, two materials that may be handled and/or treated in a similar manner might react adversely if they are combined with one another. Thus, in further embodiments, determination of the waste categories can also depend on the combinability of materials exhibiting one or more of the above characteristics.
[0150] Once a series of unique waste categories is established, lists of known pharmaceuticals, chemicals, materials and waste items can be selectively assigned to at least one of the waste categories. In some embodiments, as discussed above, when a waste item is presented to a sorting station, the item is identified according to a waste item identifier. Such identifiers can include a trade name, a generic name, a National Drug Code (NDC), one or more components or ingredients of the item, or any other sufficiently unique or relevant waste-identifying datum. Thus, a category database can be developed which correlates a number of known waste identifiers with respective waste categories according to existing federal, state, local, institution-specific or other rules and regulations.
[0151] In some embodiments, it may also be desirable to provide a database which lists ingredients of a plurality of known pharmaceuticals or other chemicals that have not yet been correlated to a waste category by the category database. Such an ingredient database can be used by the sorting algorithm in an intermediate step between identifying an item and assigning the item to a category on the basis of one or more ingredients. In some embodiments, an ingredient database may reside within the waste sorting and disposal system. In alternative embodiments, an ingredient database can reside at a remote location, such as on a server operated by a manufacturer of a particular item, or another remote location. The waste sorting and disposal system can be configured to access such remote databases via any available network, including the internet.
[0152] In some embodiments, on a first level, assignment of waste items to waste categories can be performed simply by sorting the items according to known characteristics. In some embodiments, a waste sorting algorithm simply involves locating a waste item identifier in a look-up table or database which lists known identifiers correlated to respective waste categories, such as the category database described above. Thus, to the extent that an item can be assigned to a waste category based solely on one or more waste item identifiers, the sorting algorithm can comprise a simple look-up routine. If needed, the sorting algorithm may also seek additional information such as from the ingredient database described above, or any other available source of additional information.
[0153] Cases may arise where a single waste item possesses two or more waste identifiers (such as ingredients) belonging to two or more different waste categories. Thus, in the event that a particular waste item can reasonably be assigned to two or more waste categories, yet is only physically capable of being placed in a single container, the waste sorting algorithm can be configured to assign the item to a single category by reviewing a number of secondary variables. Such secondary variables may include a dosage or quantity of specific ingredients; a dilution or concentration level of one or more ingredients; a relative hazardousness level of one or more specific ingredients; a relative reactiveness of one or more ingredients; a shape, size, type or other feature of a waste item container (e.g., a pill bottle, syringe, etc); a physical property of the item (e.g., liquid, solid or gas), or any other datum that may be available to a user, but that might not be automatically determinable by the sorting station. If such a piece of additional information is needed in order to complete an assignment of an item to a container, the sorting station can prompt a user to input further information. Such additional information can be input by selecting from multiple answer choices or by typing.
[0154] FIG. 24 is a flow chart illustrating one embodiment of a sorting algorithm. In the illustrated embodiment, a user initiates the process by presenting 300 a waste item to be identified by the sorting station. The sorting station then detects 302 a waste item identifier in any manner discussed above, such as scanning a barcode, reading an RFID tag, or scanning a textual or graphic label. The system then searches 304 the category database using any information or identifier determined from the item in an attempt to discover whether the determined identifier has previously been correlated to a waste category. If the identifier is found 306 to have been correlated to a waste category, the system continues by assigning the item to the appropriate waste category, and facilitating disposal of the item in the appropriate container.
[0155] On the other hand, if the identifier is not found in the category database (e.g., if the system discovers that the determined waste item identifier is insufficient to determine an appropriate waste category), the system may search an ingredient database 308 for additional information or further details about the item. If additional information is found 320 in an ingredient database, the additional information, along with the originally-detected waste item identifier can be used to again search the category database 322 . If this information is found to be sufficient 324 to assign the item to a waste category, then the system assigns the item 326 to that category, determines an appropriate container 328 and facilitates disposal 330 of the item in a container associated with the assigned category. The system can also store 340 the identifier/category assignment combination in the category database for use in accelerating the sorting of future waste items with the same identifier.
[0156] However, if the search of the ingredient database yields insufficient information to assign the item to a waste category, the system may seek additional information by prompting a user 342 to input additional information. Such a prompt may request specific information, such as a choice between known alternatives, or may be more general in nature. The information received 344 from the user can then be combined with previously-obtained information about the item, and the category database can again be searched in an attempt to assign the item to a category. If this information, in combination with the previously-obtained information, is sufficient to assign the item to a waste category 346 , then the system assigns the item 326 and facilitates disposal 330 of the item in the appropriate container. As above, the system can also store 340 the identifier/category assignment combination in the category database for use in accelerating the sorting of future waste items with the same identifier.
[0157] If the information received 344 from the user is insufficient 346 for the system to make a category assignment, the system can either prompt the user for still more information 342 , or the system can simply assign 350 the item to the most conservative waste category for disposal of the item as hazardous waste.
[0158] FIG. 25 illustrates one embodiment of a portion of a sorting algorithm which can be used in determining the best container for a particular item. Once the sorting algorithm has assigned an item to a waste category, the system determines 328 the container type associated with the assigned waste category. In the illustrated embodiment, the station searches the stock of the containers currently loaded into that station to determine whether the assigned container type is present in that particular sorting station 360 . If the container type is present, the station proceeds to indicate 362 the appropriate container to the user, and the user may then deposit 330 the item into the selected container. However, in some embodiments, if the selected container type is not present, the station can assess 366 whether another sorting station nearby contains a container of the assigned type. If a station with the selected container is nearby, the system can direct the user 370 to the nearby station to deposit the item. If a station with the selected container type is not nearby, the system can re-assign 368 the waste item to the most conservative (e.g., the highest level hazardous waste) category for which a container is loaded into the station.
[0159] In an alternative embodiment, a station may indicate that the selected container is full and thus cannot accept any further waste items. In such a case, the station can instruct the user to replace container with an empty one of the same type. Alternatively, the station can instruct the user to use a container in a nearby station. In some embodiments, the station may offer the user a choice between replacing a container and using a nearby station.
[0160] The term “nearby” is a relative term, and can include any actual distance deemed appropriate by a particular user or system administrator. For example, in some embodiments, a station located on another floor of the hospital may be considered nearby, while in other embodiments, a sorting station across the hallway may not be considered nearby for the purposes of re-directing disposal of the waste item.
[0161] In some embodiments it may be inappropriate or undesirable to re-assign an item to a higher level container in the event that an appropriate waste category cannot be determined (e.g., as in step 350 of FIG. 24 ), or that an appropriate container cannot be located within an acceptable proximity (e.g., in step 368 of FIG. 25 ). In such embodiments, it may be desirable to provide a temporary holding space for items that cannot be placed in any currently present container. Such items can then be analyzed at a later time by a hazardous waste analyst in order to determine the most appropriate disposal of the item. Once such an analysis is performed, the analyst preferably enters such information into the category database in order to facilitate future sorting of items having similar characteristics.
[0162] In some embodiments, the waste sorting software can be configured to maintain a log file of all identified waste items and the categories/containers to which each item was assigned. Such information can be used by hospital administrators, regulatory auditors, pharmacists, or other entities to determine what items were disposed of and how. This information can be used to further optimize the sorting algorithm, to audit compliance with regulations, to audit usage or disposal of specific items, to alter a container arrangement in a station to increase sorting efficiency, or any of a variety of other purposes.
[0163] By enlisting the use of one or more embodiments of the present system, hospitals can demonstrate to their communities and their staff that they are participating in the improvement of the environment. It has been demonstrated by the US Geological Survey that the groundwater in the United States is contaminated with drugs. Although in trace amounts, the cumulative effect of these contaminants have been shown to be endocrine system disrupters contributing to the rise in cancers, birth defects and other ailments. By properly sorting the spent drugs into appropriate containers, the waste can be properly processed in order to leave only an inert residue that cannot contaminate the ground water.
[0164] Thus, embodiments of a medical waste sorting and disposal system advantageously provide a convenient means for clinicians to automatically sort pharmaceutical waste streams in order to comply with RCRA without the need to manually classify and sort each item individually. Additionally, the system advantageously provides hospitals with a means for participating in the improvement of the environment while avoiding fines for non-compliant waste disposal methods.
[0165] Additionally, as described above, some embodiments of the system can be configured to create a manifest to provide administrators suitable tracking information on the amount of a drug that has been actually used. Many hospitals are now moving toward implementing drug dispensing automation. The automation provides the hospital pharmacist and administrator information on what drugs are dispensed but not a convenient way of generating information on how much of a drug is used.
[0000] Medical Waste Treatment System
[0166] In one embodiment, a medical waste treatment system is provided. The medical waste treatment system is a product that renders infectious waste non-infectious, compacts it to a fraction of the original volume and uniquely maintains the treated material in a compact form. The cost of present embodiments of a medical waste treatment system is much less than competing technologies, because the footprint of the equipment is, in one embodiment, about one fourth the size. Competing technologies have cycle times that are long (usually about one hour) which necessitate large vessels for acceptable throughput versus the medical waste treatment system which has a cycle time of less than five minutes.
[0167] In one embodiment, the operating cost goal (about $0.09/lb) will be equal or better than most common technology, autoclave sterilization. Other competing technologies may have lower operating costs but they have many drawbacks. Incinerators have lower operating costs ($0.02/lb-0.04/lb) but it is possible that the EPA may tighten regulations and force many of the remaining incinerators to shut down. Many states do not allow incinerators to operate within their boundaries. For example, much of California's infectious waste is trucked to a Kansas City incinerator. The transportation costs add to the actual operating costs. Plasma technologies have equipment costs that are very high ($1-$3 million) and are, therefore, only suitable for central processing plants.
[0168] In one embodiment, a medical waste treatment system as a truck mounted service to hospitals is provided. The medical waste treatment system has significant advantages over truck mounted chemical processors. The medical waste treatment system unlike the chemical processors has a residue that is substantially innocuous such as common sand. It has been demonstrated that if there are any concentrations of organic matter, such as blood, the chemicals tend to be consumed by the organics leaving some of the remaining waste in a load untreated or partially treated. In one embodiment, the medical waste treatment system uses a unique heat technology that quickly and uniformly decontaminates the waste regardless of the amount of organics present. In several embodiments, the heat technology comprises use of sand or wax (including, but not limited to, paraffin) or a combination thereof In one embodiment, the sand and/or wax is heated to a temperature of about 150° C. to about 250° C., preferably between about 165° C. to about 225° C. In one embodiment, the sand and/or wax is heated for less than about five minutes. One particular advantage of this method is the ability to produce highly stiff and/or compacted medical waste. In some embodiments, the volume and/or surface area of the treated medical waste is reduced to about 1/10 of its original size.
[0169] Up to about 50% of infectious medical waste can be plastic content, of which about 25% can include disposable PVC waste. Utilizing sand or wax to treat such plastic waste may not be any more cost effective than an Autoclave or other processing approach for these materials. It also may cause a number of problems such as the PVC outgassing chlorine because the temperature may be greater than 320 degrees ° F. (the effective melting temperature of PVC).
[0170] Thus, in one embodiment, a potential processing system for such plastic waste includes a rough grinder to grind the heterogeneous infectious medical waste into 2″ by 5″ strips. A second grinder grinds the waste into small pellets that are less than 0.25″ in diameter. The waste pellets are mixed with a whitening agent and moisture that in the presence of UVC and/or UVA will cause an oxidative reaction which in turn will denature protein or organics, thereby inactivating some if not all of the microorganisms or spores present in the pelletized waste. This will set up the microorganisms and spores for a shorter sterilization procedure.
[0171] In some embodiments, the moisture can be removed by a desiccant dryer that may be heated and then conveyed to a hopper of a plastic extruder. The extruder can be set to temperature less than 320 degrees F. but hot enough to melt the PVC. Plasticizers and other additives may be introduced to get the heterogeneous pelletized mix of waste to flow homogeneously and not clump or dissociate. This process is also the final sterilization procedure. Many of the states have adopted a document called the STAAT II sterilization guideline that spells out the amount of reduction of spores and microorganisms required for sterilization.
[0172] In some embodiments, the effluent from this plastic-treating process could then be used as a filler for a product that is extruded rather than being placed in a land fill. Reducing disposal of solid waste is desirable because of the cost (0.02 to 0.05 cents per pound). One such product is a security fence that is composed of a hollow extrusion that forms posts and walls. The center is filled with extruded hospital waste that will provide the hollow extrusion with more weight and structural integrity. In another embodiment, a sandwich of compressed mylar sheets can be applied to the exterior of the fence to render the wall bullet resistant or proof.
[0173] Other embodiments are possible, for example freeway dividers, gaskets, ashphalt filler for roads or any proprietary design that incorporates previously extruded hollow profiles that are filled with the extruded sterilized infectious medical waste can be used.
[0000] Medical Waste-Water Monitoring System
[0174] In one embodiment, a medical waste water management system is provided. In one embodiment this system is a water quality sampling service that is supplied to hospitals, clinics and labs. The product would be installed at the P trap of a sink. The medical waste-water monitoring system would sense water draining and a sample of water would be directed to a cuvette on a carousel. The samples could be taken randomly or in some predetermined sequence at a number of different sinks throughout a facility. The carousel of cuvettes would be removed, and then sent to an inside or outside lab for analysis. The analysis would pinpoint the location of any water pollution. Training classes to reinforce the proper disposal of pharmaceuticals are provided according to one embodiment of the invention. The service would continue on a less frequent basis once clinician habits had improved.
[0175] Despite a plethora of federal, state and local regulations, many clinicians continue to inappropriately dispose of pharmaceuticals in the sink. This is especially true of pharmaceutical spiked IV fluids. Verification of this practice has been established in a recent market research effort with 150 hospitals in which 60% of the respondents admitted to inappropriate disposal of drugs down the drain.
[0176] One advantage of several embodiments of this system is that it can pinpoint the source of the infraction. By combing this service along with the other Company products and services, the Company will have a sustainable competitive advantage.
[0000] Air Quality Monitoring System
[0177] The air quality monitoring system is a service that utilizes a device to sample the air quality, primarily in the pharmacy, oncology and operating room areas. It is intended to detect hazardous drugs including chemotherapeutics and anesthetics that become volatilized. The service is intended to provide clinicians with drug specific air quality information. The service will also suggest ways of eliminating the contaminants with both devices and a change in protocol. One advantage of some embodiments of this approach is that drug specific information that can be obtained.
[0000] Hospital Hazard Prevention
[0178] According to the Bureau of Labor Statistics, hospitals and nursing facilities are among the most hazardous work environments. Each year, an average of seven occupational injuries or illnesses out of 100 employees occurs. About half result in lost work time. Working with or exposure to toxic chemicals is the single largest contributing risk factor associated with occupational injury and illness in healthcare
[0179] Although nanoemulsion disinfectants and microfiber materials for cleaning and disinfection have worked successfully to reduce toxicity, much opportunity remains to improve the hospital environment, making it safer for the healthcare worker. Reducing hospital hazards will also result in savings to the hospital.
[0180] In one embodiment, a system for a service to analyze and implement reductions in hospital hazards is provided. Implementing the solutions with hospital personnel will be a process similar to making cost reductions in organizations with significant numbers of administrative procedures.
[0181] Although certain embodiments and examples have been described herein, it will be understood by those skilled in the art that many aspects of the methods and devices shown and described in the present disclosure may be differently combined and/or modified to form still further embodiments. Additionally, it will be recognized that the methods described herein may be practiced using any device suitable for performing the recited steps. Such alternative embodiments and/or uses of the methods and devices described above and obvious modifications and equivalents thereof are intended to be within the scope of the present disclosure. Thus, it is intended that the scope of the present invention should not be limited by the particular embodiments described above, but should be determined only by a fair reading of the claims that follow. | A system for sorting composite waste is provided. In some embodiments, the composite waste comprises two or more drugs, or two or more components. Composite waste is sorted efficiently and effectively using information regarding the different components in said waste, thus enabling proper disposal. | 0 |
BACKGROUND OF THE INVENTION
(a) Field of the Invention
This invention relates to the hydrofromylation of olefins, and to novel catalysts useful in such hydroformylation reactions.
(b) Description of the Prior Art
This process, often referred to as the OXO reaction, involves reaction of olefins with carbon monoxide and hydrogen in the presence of a suitable catalyst. It involves the addition of H and CHO across the double bond of the olefin, hence the term hydroformylation. The aldehyde may be further hydrogenated, either in situ by the same catalyst or in a separate reaction step, as shown in the following reaction scheme: ##STR1## In general, alcohols are the most important products, but aldehydes can be useful chemical intermediates. This is well illustrated in the hydroformylation of propylene, where n-butyraldehyde is both hydrogenated to n-butanol and converted, via aldol condensation, to 2-ethyl-1-hexanol, as shown in the following reaction scheme: ##STR2##
With olefins other than ethylene, a mixture of isomeric aldehydes is produced. From a commercial standpoint, maximum selectivity to the normal, straight-chain product is desirable. The reasons for preferring the n- over the iso- product relate to chemical utility and improved performance in the end product. Thus, in the hydroformylation of propylene, the isobutyraldehyde, readily separable from n-butyraldehyde, is not a useful product and, if present in large amount, may need to be disposed of. For higher molecular weight materials, e.g. C 8 -C 10 alcohols used in plasticiser manufacture, typically as diethylphthalates, and C 12 -C 16 alcohols in detergents, typically as alcohol ethoxylates, RO(CH 2 CH 2 O) x H, separation is difficult and the product mixture is generally used without purification. For detergents, linear alcohols mimic the natural systems with which they compete, e.g. alcohols derived from coconut oil, and are more easily biodegraded than their branched isomers. Price and performance are however always balancing considerations. Thus, for plasticisers, the branched 2-ethyl-hexanol (from C 3 H 6 via n-C 3 H 7 CHO) competes with n-octanol (from the more expensive heptene) largely on the basis of cost as a prime consideration.
The hydroformylation reaction was first operated using supported cobalt catalysts, but it is now known that homogeneous systems (using e.g. homogeneous cobalt or rhodium catalysts) are better than heterogeneous ones.
The patent literature is replete with patents alleging improved catalysts for hydroformylation and improved hydroformylation processes. Among those patents, the following non-exhaustive list may be mentioned.
CANADIAN PATENTS
(1) 729,213 issued Mar. 1, 1966, to Charles R. Greene and Robert E. Meeker, for PROCESS FOR OLEFIN HYDROFORMYLATION;
(2) 820,341 issued Aug. 12, 1966 to John L. Van Winkle, for HYDROFORMYLATION OF OLEFINS;
(3) 905,988 issued July 25, 1972 to Keith G. Allum, Ronald D. Hancock, Samuel McKenzie and Robert C. Pitkethly, for HYDROFORMYLATION PROCESS;
(4) 951,738 issued July 23, 1974 to Pudens L. Ragg, for HYDROFORMYLATION OF OLEFINS;
(5) 1,022,934 issued Dec. 20, 1977 to Donald E. Morris and Harold B. Tinker, for HYDROFORMYLATION PROCESS;
(6) 1,082,722 issued July 29, 1980 to Jerry D. Unruh and William J. Wells, III, for HYDROFORMYLATION CATALYSTS;
(7) 1,123,859 issued May 18, 1982 to Edward B. Hackman, Larry D. Zeagler, James S. McLaughlin and Carl M. Peabody, for HYDROFORMYLATION PROCESS IMPROVED BY CHOICE OF REACTION SOLVENT AND CONTROL OF PRODUCT STRIPPING PARAMETERS; and
(8) 1,191,864 issued Aug. 13, 1985 to Petrus W. N. M. Van Leeuwen and Cornelis F. Roobeek, for PROCESS FOR THE HYDROFORMYLATION OF OLEFINS.
U.S. PATENTS
(1) U.S. Pat. No. 3,239,566, patented Mar. 8, 1966 by Lynn H. Slaugh and Richard D. Mullineaux for HYDROFORMYLATION OF OLEFINS; p (2) U.S. Pat. No. 3,278,612, patented Oct. 11, 1966 by Charles R. Greene for OXO PROCESS USING COBALT CARBONYL AND TERTIARY PHOSPHINE UNDER BASIC CONDITIONS;
(3) U.S. Pat. No. 3,310,576, patented Mar. 21, 1967 by Joseph Kern Mertzweiller and Horace Marion Tenney for HYDROFORMYLATION CATALYST AND PROCESS RELATING THERETO;
(4) U.S. Pat. No. 3,515,757, patented June 2, 1970 by John W. Silbert for ORGANIC COMPOUNDS AND PROCESSES;
(5) U.S. Pat. No. 3,576,881, patented Apr. 27, 1971 by William L. Sena, Jr. for PREPARATION OF MODIFIED OXO CATALYST AND PROCESS RELATING THERETO;
(6) U.S. Pat. No. 3,917,661, patented Nov. 4, 1975 by Roy L. Pruett and James A. Smith for HYDROFORMYLATION OF UNSATURATED ORGANIC COMPOUNDS;
(7) U.S. Pat. No. 3,954,877, patented May 4, 1976 by Robert M. Gipson for HYDROFORMYLATION OF OLEFINS;
(8) U.S. Pat. No. 3,965,192, patented June 22, 1976 by Frank B. Booth for HYDROCARBONYLATION PROCESS;
(9) U.S. Pat. No. 3,976,596, patented Aug. 24, 1970 by Marion F. Hawthorne and Timm E. Paxson for HYDRIDOMETALLIC CARBORANE CATALYTIC COMPOUNDS.
(10) U.S. Pat. No. 4,041,082, patented Aug. 9, 1977 by Takeru Omoda and Tetsuo Masuyama for PROCESS FOR PRODUCING ALDEHYDES;
(11) U.S. Pat. No. 4,052,461, patented Oct. 4, 1977, by Harold Burnharm Tinker and Donald E. Morris for HYDROFORMYLATION PROCESS;
(12) U.S. Pat. No. 4,089,881, patented May 16, 1978 by Charles M. Lukehart for COMPLEXES OF METALLATED COORDINATION LIGANDS;
(13) U.S. Pat. No. 4,089,727, patented July 4, 1978 by Werner O. Haag and Dwayne Waichurst for INSOLUBLE POLYMERS HAVING FUNCTIONAL GROUPS CONTAINING CHEMICALLY BONDED GROUP VIII METAL;
(14) U.S. Pat. No. 4,139,565, patented Feb. 13, 1979 by Jerry D. Unruh and Leslie E. Wade for HYDROFORMYLATION USING IMPROVED CATALYSTS COMPRISING RHODIUM AND DIPHOSPHINO LIGANDS;
(15) U.S. Pat. No. 4,155,939, patented May 22, 1979 by John E. Poist for HYDROFORMYLATION PROCESS;
(16) U.S. Pat. No. 4,169,861, patented Oct. 2, 1979 by O. Richard Hughes for HYDROFORMYLATION PROCESS;
(17) U.S. Pat. No. 4,200,592, patented Apr. 29, 1980 by Rosemary R. Hignett and Peter J. Davidson for CATALYTIC HYDROFORMYLATION;
(18) U.S. Pat. No. 4,201,714, patented May 6, 1980 by O. Richard Hughes for STABILIZED CATALYST COMPLEX OF RHODIUM METAL, BIDENTATE LIGAND AND MONODENTATE LIGAND;
(19) U.S. Pat. No. 4,201,728, patented May 6, 1980 by O. Richard Hughes for HYDROFORMYLATION CATALYST AND PROCESS;
(20) U.S. Pat. No. 4,285,215, patented Mar. 24, 1981 by John I. Dawes for HYDROFORMYLATION PROCESS;
(21) U.S. Pat. No. 4,291,196, patented Sept. 29, 1981 by Edwin H. Homeier, Alan R. Dodds and Tamatsu Imai for CATALYST RECOVERY;
(22) U.S. Pat. No. 4,386,013, patented May 31, 1983 by Kenneth P. Callahan, Peter M. DiGlacomo and Martin B. Dines for HYDROFORMYLATION PROCESS UTILIZING NOVEL CATALYST;
(23) U.S. Pat. No. 4,399,312, patented Aug. 16, 1983 by Michael J. H. Russel and Barry A. Murrer for CATALYTIC PROCESS;
(24) U.S. Pat. No. 3,937,742, patented Feb. 10, 1976 by Jin Sun Yoo for HYDROFROMYLATION PROCESS USING CATALYST COMPRISING PLATINUM GROUP METAL ON SUPPORT HAVING SEPARATE ALUMINA PHASE;
(25) U.S. Pat. No. 4,358,621, patented Nov. 9, 1982 by Tadamori Sakakibara, Yoshihisa Matsushima and Katsumi Kaneko for PROCESS FOR PRODUCING ALDEHYDES;
(26) U.S. Pat. No. 4,108,905, patented Aug. 22, 1978 by Geoffrey Wilkinson for CATALYTIC REACTIONS;
(27 ) U.S. Pat. No. 4,298,541, patented Nov. 3, 1981 by Alexis A. Oswald and Andrew A. Westner, TRIHYDROCARBYL SILYL-SUBSTITUTED ALKYL DIARYL PHOSPHINE TRANSITION METAL COMPLEXES AND THEIR USE AS HOMOGENEOUS CATALYSTS;
(28) U.S. Pat. No. 4,400,548, patented Aug. 23, 1983 by Anthony G. Abatjoglou and Ernst Billig, HYDROFORMYLATION PROCESS USING BISPHOSPHINE MONOOXIDE LIGANDS; and
(29) U.S. Pat. No. 4,450,299, patented May 22, 1984 by Alexis A. Oswald, Torris G. Jermansen, Andrew A. Westner and I-Deo Haang for HOMOGENEOUS HYDROFORMYLATION CATALYSTS WITH SILYL SUBSTITUTED ALKYL DIARYL PHOSPHINE METAL COMPLEXES.
In summary, among the catalysts proposed by the above noted patents are the following: dicobalt octacarbonyl per se or in various modified forms; certain transition metal complexes with biphyllic ligands, e.g. complexes of cobalt with carbon monoxide and tribytyl phosphite or triphenyl phosphine; a metal complex catalyst having incorporated therein a biphyllic ligand, e.g. carbon monoxide in conjunction with other selected biphyllic ligands and in particular phosphines e. g., tributyl phosphine or triphenyl phosphine; cobalt in complex combination with carbon monoxide and tertiary organophosphines; compounds containing transition metals bonded to phosphorus and silicon; a metallated polymer of a styrylphosphine having Group VIII metal atoms coordinated to the phosphorus atoms; an ionic rhodium complex Rh(CO) x L y An, the ionic compound comprising a complex cationic rhodium moiety Rh(CO) x L y and a non-coordinating anionic moiety An; a Group VIII metal in complex combination with a monodentate or polydentate ligand comprising a triorganophosphine, triorganophosphite, triorganoarsine, or triorganostibine moiety; a ligand-stabilized-platinum-containing catalytic system comprising at least a secondary phosphine oxide moiety; a catalyst comprising ruthenium and/or rhodium in complex combination with carbon monoxide and a phosphorus-containing ligand consisting essentially of a tertiary organo phosphorus compound in which the phosphorus is trivalent; a cobalt carbonyl tri-n-butyl phosphine; a complex which contains a transition metal selected from Group VIII in complex bond with at least one carbon monoxide molecule, at least on biphyllic ligand which contains an atom selected from Group V-A, and a ligand consisting of a conjugated diolefin adduct; a rhodium complex, e.g. hydridocarbonylbis(triphenylphosphine)dichlororhodium; complex metal carbonyl compounds having the generic formula M 2 (CO) 2 (XR 3 ) 2 wherein M is iron, cobalt or rhodium, X is phosphorus or arsenic, and R is an alkyl or alkoxy radical having from 1 to 20 carbon atoms; rhodium in complex combination with carbon monoxide and a ligand containing a trivalent atom of a Group VA element including phosphorus, arsenic, and antimony; a complex Group VIII catalyst modified by incorporating therein a catalyst modifier of pentavalent phosphorus arsenic or antimony; a catalyst comprising a complex between an organic ligand and a Group VIII noble metal hydride carbonyl; a complex combination of a Group VIII noble metal hydride with carbon monoxide and an organic ligand; a rhodium-tertiary phosphine complex; organometallic complexes which contain at least two metal atoms, or a metal atom and a proton, and at least one ligand representing a metallated unsaturated chelating six-membered ring system, where the metallation involves the formal replacement of a methine group by an organometallic complex; a rhodium catalyst in the form of an ionic rhodium compound, consisting of a rhodium-containing cation having rhodium complexed with ligands other than halide, and a non-coordinating anion; an insoluble polymer containing a functional group, which may be an amine, thiol, phosphine, or arsine group, having chemically bonded thereto a metal of Group VIII; rhodium hydrido carbonyl in complex combination with a diphosphino-substituted ligand; a ligand stabilized complex of platinum dihalide dimer and stannous halide; a stabilized catalyst complex of rhodium metal, bidentate ligand and specified monodentate ligand; a complex of Rh(I) in solution and a homogeneous co-catalyst dissolved in the solution and comprising a co-ordination complex of a transition metal other than rhodium selected from Group 6 or Group 8 of the Periodic Table; metal carbonyls or organometallic complexes in which the metal portion of the complex is selected from Group VIII metal; a composite of rhodium metal or a rhodium metal compound and a compound selected from the group consisting of compounds represented by the general formula M(O 3 ZO 2 R) 12 , wherein M comprises a tetravalent metal, Z comprises a pentavalent atom, R is selected from the group consisting of organo radicals comprising a moiety selected from the group consisting of phosphine radicals; x is 0 or 1, and n is 2; a catalyst containing a hydrido-platinum group metal-carbonyl, e.g. hydridopalladium carbonyl, on a solid, acidic, silica-based support material, also containing a Group VA electron donor ligand, e.g. triphenyl phosphine; a Pt Group IV-A organometallic catalyst mixture, e.g. (PPh 3 ) 2 PtPhSnPh 2 Cl/SnCl 2 ; a hydrido carbonyl complex of rhodium which includes two phosphorus-containing stabilizing donor ligands selected from the group consisting of triphenyl phosphine an triphenylphosphite; homogeneous trihydrocarbyl silyl-substituted alkyl diaryl phosphine transition metal complexes of the general formula: [(AR 2 PPO) 3 SiR 4 ] g (MX n ) y , wherein Ar is a C 6 to C 10 aromatic hydrocarbyl radical, Z is a C 3 to C 30 saturated straight chain divalent radical, R is an unsubstituted C 1 to C 10 hydrocarbyl, C 1 to C 10 monosubstituted hydrocarbyl phenyl radical, y is 1 to 4, g times y is 1 to 6, M is a transition metal selected from the group consisting of Group VIII transition metals, X is an anion or organic ligand excluding halogen satisfying the coordination sites of the metal, n is 2 to 6 and s is 1 to 3; and trihydrocarbyl silyl-substituted alkyl diaryl phosphine transition metal complexes.
SUMMARY OF THE INVENTION
(a) Aims of the Invention
In spite of all these patented catalysts which were said to have solved myriad problems in hydroformylation processes, including improving catalyst stability, improving catalyst activity by avoiding the necessity for the use of exceedingly high pressures, speeding up the slow rate of hydroformylation while maintaining high selectivity at temperatures conducive to high conversion levels and high reaction rates, the improvement of the linear/branched product ratio, or to provide soluble catalysts, there remains a need for hydroformylation catalysts and processes which provide for olefin conversion to aldehyde products with improved efficiency and selectivity at lower carbon monoxide pressures, and with a concomitant reduction in the yield of isomerization, hydrogenation, and polymerization products.
Several of the above patents refer to the use, as ligands, of compounds containing P and Si connected by one or more CH 2 groups. Specifically, the above patents appear to deal exclusively with metal complexes in which the phosphinoalkylsilyl fragment is attached through P only, rather than in a cyclic unit attached by P and Si as in the complexes used in the hydroformylation process of aspects of the present invention which will be discussed in detail later.
One object of the present invention is the provision of an improved hydroformylation process enabling the more efficient production of desired products by rapid hydroformylation reactions of olefinic compounds with carbon monoxide and hydrogen in the presence of a new and improved hydroformylation catalyst.
Still another object of the present invention is the provision of an improved hydroformylation process enabling the efficient single stage production of aldehydes by reaction of olefinic hydrocarbons with carbon monoxide and hydrogen in the presence of an improved and more stable catalyst, facilitating product isolation, catalyst recovery, and recycle steps without substantial decomposition and loss.
Yet another object of this invention to provide a novel hydroformylation catalyst which promotes the conversion of olefins to aldehydes with a high rate of reaction and a high level of conversion.
A further object of this invention is to provide an improved hydroformylation process for converting alpha-olefins to linear aldehydes with improved efficiency and selectivity.
(b) Statements of Invention
By this invention, a novel hydroformylation process is provided for the conversion of an having up to about 20 carbon atoms to a corresponding aldehyde, which process comprises: reacting the olefinic compound in the liquid phase with carbon monoxide and hydrogen at a temperature between about 60° and about 200° C. and at a pressure of up to about 1000 psi or more in the presence of a catalyst comprising a chelate in which a ligand is chelated at a metal center to produce at least one heterocyclic ring with the central metal atom as part of the ring, the catalyst being selected from the group consisting of
(A) a platinum group metal complex of bis (phosphinoalkyl)silane having the following Formula I: ##STR3## wherein: Ar is alkyl, phenyl or modified aryl, cyclohexyl or C 6 H 4 X
X is Cl, Br, F, CO 2 CF 3 , or SnCl 3 ;
R is Me, Et, n-Br, t-Bu or cyclohexyl or phenyl;
M is an operative metal selected from the group consisting of Pt, Pd, Rh, and Ir; and
( ) n is 2, 3, or 4, thereby to provide 2, 3 or 4 C atoms respectively between Si and P:
(B) a platinum-group metal complex having the Formula II ##STR4## wherein Ar, X, R, M and ( ) n are as defined above;
(C) a platinum-group metal complex having the Formula III ##STR5## wherein Ar, X, R, M and ( ) n are as defined above;
(D) a platinum-group metal complex having the Formula IV ##STR6## wherein Ar, X, R, M and ( ) n are as defined above;
(E) a platinum-group metal complex of the Formula V ##STR7##
(F) a platinum-group metal complex of the Formula VI ##STR8## wherein Ar, X, R, M and ( ) n are as defined above;
(G) a platinum-group metal complex of tris(phosphinoalkyl) silane having the following Formula VII ##STR9## wherein Ar, X, M and ( ) n are as defined above;
(H) a platinum-group metal complex having the Formula VIII ##STR10## wherein Ar, M and ( ) n are as defined above, and Y=CO, P(Ar) 3 , or a similar neutral ligand molecule;
(I) a platinum-group metal complex of the Formula IX ##STR11##
(J) a platinum-group metal complex of the Formula X ##STR12##
(K) a platinum-group metal complex of the Formula XI ##STR13##
(L) a platinum-group metal complex of the Formula XII ##STR14##
(M) a platinum-group metal complex of the Formula XIII ##STR15## and
(N) a platinum-group metal complex of the Formula XIV ##STR16##
Specific embodiments of the catalysts used in the abovedescribed hydroformylation process of this invention include the following: ##STR17##
With respect to the olefins which may be subjected to the hydroformylation process of the present invention, in general α-olefins, although more expensive than the counterpart internal olefins, are the preferred feedstocks in that they give a much higher proportion of the desired linear product.
With olefins higher than propylene, it was found that catalysts used heretofore may tend to isomerise the double bond along the hydrocarbon chain and this may lead to the production of a number of additional branched products.
The unsaturated carbon-to-carbon olefinic linkages may be between terminal and their adjacent carbon atoms, as in 1-pentene, or between internal chain carbon atoms, as in 4-octene. It may also be possible to use olefinic hydrocarbon fractions. If desired, suitable such feeds consisting of olefinic hydrocarbon fractions include, for example, C 7 , C 8 , C 9 , C 10 and higher olefinic fractions as well as olefinic hydrocarbon fractions of wider boiling ranges, e.g. C 7-9 , C 10-13 , C 14-17 olefinic hydrocarbon fractions and the like.
According to the present invention, examples of useful olefins include the following: ethylene, propylene, butylene, butylene, butene-1, butene-2, pentene-1, benzenes, 2-methylbutene-1, cyclobutene, hexene-1, hexene-2, heptenes, ethyl pentenes, octenes, decenes, nonenes, dodecene, 1-octadecene, dihydronaphthalene, cyclohexene, 3-ethylhexene-1, isobutylene, octene-1, 2-propylhexene-1, ethylcyclohexene, decene-1, cycloheptene, cyclooctene, cyclononene, cyclodecene, cyclododecene, 2-ethyl-1-hexene, styrene, 3-phenyl-1-propene, allyl chloride, 1,4-chloride, 1,4-hexadiene, 1,7-octadiene, 3-cyclohexyl-1-butene, allyl alcohol, hex-1-en-4-ol, oct-1-en-4-ol, vinyl acetate, allyl acetate, 3-butenyl acetate, vinyl propionate, allyl propionate, allyl butyrate, methyl methacrylate, 3-butenyl acetate, vinyl ethyl ether, vinyl methyl ether, allyl ethyl ether, n-propyl 7-octenoate, 3-butenoic acid, 7-octenoic acid, 3-butenenitrile, 5-hexenamide, 4,4'-dimethylnonene-dodecene-1, undecene-3, 6-propyldecene-1, tetradecen-2, 7-amyldecene-1, oligomers of olefins, e.g. propylene tetramer, ethylene trimer, etc., hexadecene-1, 4-ethyltridecene-1, octadecene-1, 5,5-dipropyldocecene-1, vinylcyclohexane, allylcyclohexane, styrene, p-methylstyrene, alpha-methylstyrene, p-vinylcumene, beta-vinylnaphthanene, 1,1-diphenylethylene, allylbenzene, 6-phenylhexene-1, 1,3-diphenylbutene-1, 3-benzylheptene-1, o-vinyl-p-xylene, divinylbenzene, 1-allyl-4-vinylbenzene, 1,3-butadiene, 1,4-pentadiene, 1,5-hexadiene, 1,4-heptadiene, 1,7-octadiene, 2,6-decadiene, 1,9-dodecadiene, 1,5-hexadiene, 1,4-heptadiene, 1,7-octadiene, 2,6-decadiene, 1,9-dodecadiene, 1,5-hexadecadiene, 1,4,7-octatriene, 1,4,7,10-undecatetraiene, 1,4-cycloheptadiene, 1,5-cyclooctadiene, 1,4,7-cycloderatriene, 1,5,9-cyclododecatriene, 1,5-bicyclo(2,2,2)heptadiene, 1,2-butadiene, 1,3,5-hexatriene, 2-chloro-1,3-butadiene, 2-chloro-1,3-butadiene, 3,5-monodacadiene, 1,5-hexadiene, 1,5,8-dodecatrriene, and 2,6-octadecadiene.
Of the preceeding examples, the alpha olefins and olefins having 2 to 8 carbons are preferred classes. It is preferred to use internal normal olefins, having, for example, from 4 to 19 carbon atoms to the molecule to normal terminal alcohols having 5 to 20 carbon atoms to the molecule respectively. A characteristic feature of olefins with two or more double bonds is that only one of the double bonds is hydroformylated. The remaining double bonds are hydrogenated. Preferred alpha olefinic compounds include alkenes, alkyl alkenoates, especially those which contain up to about 20 carbon atoms.
Process operating parameters employed in the process of the present invention will vary depending upon the nature of the end product desired. In general, however, the operating parameters contemplated by the process of aspects of the present invention are the same as those conventionally employed in prior art hydroformylation processes.
The preferred hydroformylation process of this invention will be that process which is most efficient in producing normal aldehyde isomer product, i.e. straight chain aldehyde as distinguised from its isomeric or branched chain aldehyde product. The optimization of the reaction conditions necessary to achieve the best results and efficiency desired will be well within the knowledge of one skilled in the art and easily obtainable by following the more preferred embodiments of this invention as explained more fully below and/or by simple routine experimentation.
In general, the hydroformylation process of this invention is conducted under a total pressure of hydrogen and carbon monoxide up to and exceeding about 250 atmospheres; the pressure is usually kept as low as possible for economic reasons. Pressures in the range of about 50 psig to about 3,000 psig, (about 50 to about 150 atmospheres) are generally satisfactory. For commercial reasons, however, pressures significantly greater than about 400 psig will not normally be employed.
The total gas pressure of hydrogen, carbon monoxide and olefinic unsaturated compound of the hydroformylation process of aspects of this invention may range from about 1 to about 10,000 psig. More preferably however the process of this invention is operated at low pressures the preferred total gas pressure of hydrogen, carbon monoxide and olefinic unsaturated compound being less than about 1500 psia, more preferably less than about 500 psia and most preferably less than about 350 psia. The minimum total pressure of the reactant gases is not particularly critical and is limited predominantly only by the amount of reaction gases necessary to obtain a desired rate of reaction. The preferred carbon monoxide partial pressure of the process of aspects of this invention is preferably less than about 200 psia, more preferably less than about 100 psia and most preferably from about 1 to about 50 psia. On the other hand, the partial pressure of hydrogen gas of the hydroformylation process of this invention is preferably less than about 500 psia, more preferably less than about 400 psia and most preferably about 20 to about 200 psia. In addition it is generally preferred that the partial pressure of carbon monoxide be less than about 75% of the total gas pressure of (CO+H 2 ). However in certain instances it may be plausible to increase the carbon monoxide partial pressure to a value above about 75% of the total gas pressure. On the other hand, in general, a partial pressure attributable to hydrogen of from about 25 to about 95% and more, based on the total gas pressure of (CO+H 2 ) should be suitable in most instances. It is further normally advantageous to employ a total gas pressure in which the partial pressure attributable to hydrogen is greater than the partial pressure attributable to carbon monoxide, e.g. a H 2 /CO molar ratio of gaseous hydrogen to carbon monoxide within any range from about 3:2 to about 200:1 or higher, the more preferred hydrogen to carbon monoxide molar ratio being from about 3:1 to about 20:1.
The other hydroformylation reaction conditions are well known to those skilled in the art and are variable over wide ranges of temperatures and pressures. In the practice of the process of this invention, the temperatures may range between from about 100° C. and about 200° C. The process according to the present invention is carried out under mild reaction temperature conditions. Temperatures in the range of from about 50° C. to about 200° C. can be suitably applied, but lower or higher temperatures can also be used. Preference is given to temperatures in the range of from about 75° C. to about 150° C.
Preferred space velocities are an olefin LHSV of from about 0.1 to about 20 and GHEV of hydrogen and carbon monoxide of about 50 to about 10,000. The lHSV or GHSV is expressed as volumes of liquid or gas per vol. of catalyst.
A reaction time between about 2 and about 5 hours is particularly preferred. The reaction may be operated batchwise or continuously.
Catalyst concentrations are not generally critical, provided that they are such that the reaction proceeds at an acceptable rate. In practice, the upper limit of concentration is dictated by economic considerations. Molar ratios of catalyst to olefin in the reaction zone at any given instant between about 1:1000 and about 10:1 are found to be satisfactory; higher or lower catalyst to olefin ratios may, however be used, e.g. between about 12:1 and about 1:12, but in general it will be about 1:1.
The ratio of hydrogen to carbon monoxide charged may vary widely. The ratio of hydrogen to carbon monoxide can vary broadly over a mole ratio range between about 30:1 and about 1:30. The average mole ratio will vary between about 10:1 and about 1:10. The quantity of hydrogen/carbon monoxide charged should be at least sufficient to satisfy the stoichiometric requirements of the olefin hydroformylation system. In general, a mole ratio of hydrogen to carbon monoxide of at least about 1 is employed. Suitable ratios of hydrogen to carbon monoxide comprise those within the range of from about 1 to about 10. Higher or lower ratios may, however, be employed. The ratio of hydrogen to carbon monoxide preferably employed will be governed to some extent by the nature of the reaction product desired. If conditions are selected that will result primarily in an aldehyde product, only one mole of hydrogen per mole of carbon monoxide enters into reaction with the olefin.
Excess carbon monoxide or hydrogen over the above-described stoichiometric amounts, however, may be present. Any ratio of H 2 to CO from about 10:1 to about 1:10 may be chosen. The preferred ratio is about 1:1 which encourages aldehyde formation.
Some of the complexes used as hydroformylation catalysts are novel per se. Other complexes have been disclosed by the present inventors, but their utility as hydroformylation catalysts have not been suggested. These disclosures include the following:
(1) "Phosphinoalkylsilanes: Synthesis and Spectroscopic Properties of Phosphino(silyl) methanes, 1-Phosphino-2-silylethanes, and 1-Phosphino-3-silylpropanes". Rupert D. Holmes-Smith, Rexford D. Osei, and Stephen R. Stobart, J. Chem. Soc. Perkin Trans. 1 1983;
(2) "(Phosphinoalkyl)silyl Complexes. 3. Chelate-Assisted Hydrosilylation: Formation of Enantiomeric and Diastereoisomeric Iridium (III) Complexes with Chelating (Phosphinoethyl)silyl Ligands". Mary J. Auburn, Rupert D. Holmes-Smith, and Stephen R. Stobart. Journal of the American Chemical Society, 1984, 106, 1314;
(3) "Intramolecular Rearrangement Behaviour of a Dihydridoiridium (III) Complex formed by Regiospecific Chelate-assisted Hydrosilylation". Mary J. Auburn and Stephen R. Stobart. Journal of the Chemical Society Chemical Communications 1984;
(4) "Phosphinoalkylsilyl Complexes. 6. Isolation of a Silyl Complex of Iridium (I). Crystal and Molecular Structure of Dicarbonyl(triphenylphosphine)-[((diphenylphosphino)ethyl)-dimethylsilyl]iridium". Mary J. Auburn, Stephen L. Grundy, Stephen R. Stobart, and Michael J. Zaworotko, J. Am. Chem. Soc. 1985, 107, 266-267; and
(5) "Phosphinoalkylsilyl Complexes, 5, Synthesis and Reactivity of Congereric Chelate-Stabilized Disilyl Complexes of RH (III) and IF (III); Chlorobis[Diphenylphosphinoethyl-(Dimethyl)Silyl]-Rhodium and -Iridium." Mary J. Auburn, and Stephen R. Stobart, Inorg. Chem. 24, 318-323 1985.
DESCRIPTION OF PREFERRED EMBODIMENTS
The following Experiments and Examples are given to illustrate the present invention.
EXPERIMENT 1
A series of phosphino(silyl)methanes, 1-phosphino-2-silylethanes and 1-phosphino-3-silylpropanes was prepared according to the procedures described in the above-identified Perkin Trans. I 1983, 861.
The compounds prepared had the following structures:
______________________________________ ##STR18##
______________________________________Ph.sub.2 PCH.sub.2 SiXYZ Ph.sub.2 PCH.sub.2 CH.sub.2 SiXYZ______________________________________ (1) X = Y = Z = Me (11) X = Y = Me,Z = Cl (2) X = Y = Me,Z = Cl (12) X = Y = Me,Z = H (3) X = Y = Me,Z = H (13) X = Me,Y = Ph,Z = Cl (4) X = Me,Y = Ph,Z = Cl (14) X = Me,Y = Ph,Z = H (5) X = Me,Y = Ph,Z = H (15) X = Y = Ph,Z = Cl (6) X = Y = Ph,Z = Cl (16) X = Y = Ph,Z = H (7) X = Y = Ph,Z = H (17) X = Me,Y = Z = Cl (8) X = Y = Z = Ph (18) X = Me,Y = Z = H (9) X = Ph,Y = Z = Cl (19) X = Ph,Y = Z = Cl(10) X = Ph,Y = Z = H (20) X = Ph,Y = Z = H (21) X = Y = Z = Cl (22) X = Y = Z = H______________________________________Ph.sub.2 PCH.sub.2 CH.sub.2 CH.sub.2 SiXYZ Me.sub.2 PCH.sub.2 CH.sub.2 SiXYZ______________________________________(23) X = Y = Z = Me (28) X = Y = Me,Z = Cl(24) X = Y = Me,Z = Cl (29) X = Me,Y = Ph,Z = Cl(25) X = Y = Me,Z = H (30) X = Me,Y = Z = Cl(26) X = Y = Z = Cl (31) X = Y = Me,Z = H(27) X = Y = Z = H (32) X = Me,Y = Ph,Z = H (33) X = Me,Y = Z = H______________________________________
The general synthesis process may be described as follows:
All synthetic manipulations were carried out using standard inert atmosphere techniques and all solvents were dried and distilled under dry dinitrogen gas. N.m.r. spectra were obtained with Perkin-Elmer R32 ( 1 H, 90 MHz), Nicolet TT-14 ( 13 C, 15.1 MHz; 31 P, 24.3 MHz), and Bruker WM250 ( 1 H, 250 MHz; 13 C, 93.6 MHz) spectrometers, I.r. spectra were recorded using a Perkin-Elmer 283 spectrophotometer.
The simple silanes, diphenylphosphine, and methyldiphenyl-phosphine were purchased (Aldrich, Strem Chemicals, or Petrarch) or synthesized by literature procedures and were distilled under dry dinitrogen gas immediately prior to use. The lithium salt LiCH 2 PPh 2 tmeda (tmeda=tetramethylethylenediamine) was prepared from methyldiphenylphosphine. Most of the new compounds deteriorated rapidly in air, the chlorosilyl derivatives being particularly sensitive. Purity of products was established by microanalysis.
EXPERIMENT 1
The following are typical of the preparative reactions.
(i) 2-Chlorodimethylsilyl-1-diphenylphosphinoethane (11)
Diphenylphosphine (1.96 g, 1.05 mmol) and chlorodimethylvinyl-silane (2.17 g, 1.66 mmol) were loaded into a quartz reaction tube fitted with a greaseless high-vacuum stopcock, which was then evacuated, placed approximately 5 cm from a medium-pressure mercury lamp and irradiated (5 h). The viscous oily liquid phase was separated from a small quantity of solid material by dissolution in dry benzene (20 cm 3 ). The solution was transferred to a Schlenk tube from which all volatile material was removed by pumping at 20° C./10 2 mmHg; the remaining fraction was evaporated (145°-150° C., 10 2 mmHg) onto a water-cooled finger to give the colourless liquid product (11)(2.30 g, 7.51 mmol, 71%).
(ii) 2-Dimethylsilyl-1-diphenylphosphinoethane (12)
To a solution of compound (11) (2.25 g, 7,.34 mmol) in dry Et 2 O (20 cm 3 ) in a Schlenk tube was added LiAlH 4 (excess) and the reaction mixture was stirred at 20° C. After 2 h, all volatiles were removed under reduced pressure and the fraction evaporating at 130°-135° C./10 2 mmHg was collected yielding the colourless liquid product (12)(1.66 g, 6.09 mmol, 83%).
(iii) Chlorodimethylsilyl(diphenylphosphino)methane (2)
Dichlorodimethylsilane (80 cm 3 ) in tetrahydrofuran (THF) (150 cm 3 ) was cooled to -78° C. and treated dropwise (2 h) with a solution of Ph 2 PCH 2 Li.tmeda (10.0 g, 31 mmol) in THF (30 cm 3 ). The mixture was warmed to ambient temperatures and all volatile material was removed under reduced pressure after which the residue was extracted with hexane (3×40 cm 3 then 3×20 cm 3 ). The extracts were combined, the solvent removed under reduced pressure, and the product evaporated (125°-130° C.) to give, on a water-cooled probe, the colourless liquid product (2) (6.4 g, 22 mmol, 7.1%).
(iv) Dimethylsilyl(diphenylphosphino)methane (3)
Compound (2) (3.4 g, 12 mmol) was added dropwise to a suspension of LiAlH 4 (0.40 g, 10 mmol) in Et 2 O (20 cm 3 ). The mixture was stirred at 20° C. (1 h), then all volatiles were removed under reduced pressure and the residue was extracted with hexane (6×15 cm 3 ). The extracts were combined and the hexane removed, and the colourless, liquid product (3) (2.5 g, 10 mmol, 83%) was collected after evaporation at 115°-120° C. by condensing it on a water-cooled finger.
(v) 3-Chlorodimethylsilyl-1-diphenylphosphinopropane (24)
Diphenylphosphine (2.20 g, 12.0 mmol) and allyldimethylchlorosilane (2.20 g, 16.0 mmol) were allowed to react in an evacuated quartz tube (8 h) under irradiation from a medium-pressure mercury lamp (ca. 5 cm distant). The product mixture was taken up in dry benzene (20 cm 3 ), transferred to a Schlenk tube, and the benzene and excess of silane were removed under reduced pressure. Material evaporating from the residue at 180°-190° C./10 2 mmHg was identified as the oily liquid product 924) (2.08 g, 6.48 mmol, 41%).
(vi) 3-Dimethylsilyl-1-diphenylphosphinopropane (25)
Compounds (24) (1.00 g, 3.12 mmol), dry Et 2 O (20 cm 3 ), and LiAlH 4 (excess) were stirred together at 20° C. (1 h) in a Schlenk tube. After the solid had settled, the supernatant layer was recovered by syringe; volatiles were removed under reduced pressure and the colourless liquid product (25) (0.81 g, 2.82 mmol, 90%) evaporated (150°-160° C./10 2 mmHg) and collected as before.
(vii) 2-[ 2 H 6 ]Dimethylsilyl-1-diphenylphosphinoethane[ 2 G 6 ]-(12)
Repetition of reaction (ii) using LiAlD 4 gave the product (84%) with >95% incorporation (i.r.) of 2 H.
(viii) 1-Diphenylphosphino-2-phenylsilylethane (20)
Irradiation (4 h) of a mixture of Ph 2 PH (1.09 g, 5.86 mmol) and H 2 Si(CH:CH 2 )Ph (0.79 g, 5.90 mmol) yielded after work-up as in (i)-(vi), the product (20) (1.18 g, 3.69 mmol, 63%).
EXPERIMENT 2
A series of phosphinoalkyl(silyl) complexes was prepared according to the description in the above-identified J. Am. Chem. Soc. 1984, 106, 1314; J. Chem. Soc., Chem. Commun. 1984, 281; Inorg. Chem. 1985, 24, 318; and J. Am. Chem. Soc., 1985, 107, 266. publications.
Experiment 1, above, described the preparation of the phosphinoethylsilanes Ph 2 PCH 2 CH 2 SiR 1 R 2 H (R 1 =R 2 =Me or Ph; or R 1 =Me, R 2 =Ph) and Ph 2 PCH 2 CH 2 SiRH 2 (R=Me or Ph) by LiAlH 4 reduction of the corresponding chloro(phosphinoethyl)silanes. In several cases, the monodeuterio- analogues were obtained similarly, using LiAl 2 H 4 . The iridium(I) complexes trans-Ir(Cl)(CO)(PPh 3 ) 2 and HIr(CO)(PPh 3 ) 3 are readily accessible by using straightforward literature methods.
The following Experiment 2 describes the synthesis of [phosphinoethyl)silyl]iridium(III) complexes.
(1a) ##STR19##
To a stirred solution of trans-Ir(Cl)(CO)(PPHh 3 ) 2 (0.50 g, 0.64 mmol) in benzene (40 mL) was added liquid Ph 2 PCH 2 CH 2 SiMe 2 H drop by drop with a syringe until the characteristic lemon-yellow color of the iridium(I) complex was completely discharged. After further stirring for 10 min, the solvent was pumped away leaving a colorless oily residue, which was dissolved in boiling hexane (35 mL). After the solution was cooled, a white solid separated from which the supernatant was carefully removed and discarded; recrystallization four times from dichloromethane/hexane mixtures afforded the product as a pure white powder, mp 160°-161° C. (0.37 g, 0.47 mmol, 73%). Anal. Calcd for C 35 H 36 ClIrOP 2 Si: C, 53.18; H, 4,56. Found: C, 52,98; H 4,67. Repeated efforts to crystallize this compound deliberately were unsuccessful; however, on one occasion well-formed colorless cube-shaped crystals which proved to be suitable for X-ray diffraction were obtained fortuitously by dissolution of the oily crude product (ca. 1.0 g) in a large excess (ca. 25 mL) of diethyl ether, followed by addition of an equal volume of hexane and exposure of the resulting clear solution to a rapid draught of cool air.
(1b) ##STR20##
The deuterio analogue (1b) of complex (1a) was prepared by treatment of a benzene solution of trans-Ir(Cl)(CO)(PPh 3 ) 2 (0.10 g, 0.13 mmol) with just sufficient Ph 2 PCH 2 CH 2 SiMe 2 2 H to cause decolorization of the former. The white product was recovered as described above. (2a) ##STR21##
Addition of a solution in benzene of Ph 2 PCH 2 CH 2 SiPh 2 H to a stirred solution in benzene (15 ml) of trans-Ir(Cl)(CO)(PPh 3 ) 2 (0.20 g, 0.26 mmol) until the reaction mixture was completely colorless was followed by removal of solvent. The white residue was washed with hexane (4×10 mL), after which crystallization from dichloromethane/heptane (4×10 mL), after which crystallization from dichloromethane/heptane afforded white microcrystals of the product, (2a) mp 174°-176° C. (0.17 g, 0.19 mmol, 72%). Anal. Calcd for C 45 H 40 ClIrOP 2 Si: C, 59.11; H, 4,38. Found: C, 58.26; H, 4.66.
(2b) ##STR22##
After dropwise addition of a solution in benzene of Ph 2 PCH 2 CH 2 SiPh 2 2 H to a stirring solution in the same solvent (15 mL) of trans-Ir(Cl)(CO)(PPh 3 ) 2 (0.10 g, 0.13 mmol) until the yellow color of the latter was discharged completely, the volume of the reaction mixture was reduced to 5 mL, and then heptane (15 mL) was added. The resulting white precipitate (2b) was thoroughly washed with heptane, then dried in vacuo to give the product as a fine white powder (0.08 g, 0.09 mmol, 67%).
(3a) ##STR23##
To trans-Ir-(Cl)(CO)(PPh 3 ) 2 (0.10 g, 0.13 mmol) dissolved in toluene (50 mL) and stirred at 60° C. was added liquid Ph 2 PCH 2 CH 2 CH 2 SiMePhH until complete decolorization occurred, after which stirring of the reaction mixture was continued for 10 min and then solvent was removed to leave a colorless oil. Addition of pentane precipitated a white solid from which was recrystallized (dichloromethane/pentane) the product, (3a) mp 112°-115° C. (0.72 g, 0.09 mmol, 65%), Anal. Calcd for C 40 H 38 ClIrOP 2 Si: C, 56.38; H, 4.46. Found: C, 57.62; H, 4,81.
(3b) ##STR24##
An identical procedure with that described above was followed using deuteriosilane Ph 2 PCH 2 CH 2 SiMePh 2 H to yield the 2 H-analogue
(4a) ##STR25##
(4b) ##STR26## and
(5) ##STR27##
These compounds were synthesized in experiments similar to those described above reacting Vaska's complex with the precursors Ph 2 PCH 2 CH 2 SiMe n H 2 (n=1 or 2) or Ph 2 PCH 2 CH 2 SiPhH 2 , respectively. Yields were ca. 50% with mp 80°-85° C. (4a, 4b) or 100°-105° C.(5); the colorless products were characterized by IR and NMR spectroscopy.
(6) ##STR28##
Method A From Complex (1a)
Complex (1a) (0.25 g, 0.32 mmol) was dissolved in THF (10 mL). After dropwise addition of a solution of LiAlH 4 (0.14 g, 3.7 mmol) in THF (15 mL) the reaction mixture was stirred overnight and then refluxed (8 h). Careful addition of MeOH to the resulting pale yellow solution afforded a colorless mixture from which all volatiles were removed. The solid residue was redissolved in the minimum of THF and filtered under a N 2 atmosphere through a plug of alumina. Slow addition of hexane precipitated the product (6) as a cream-colored powder, ca. 60% yield. Anal. Calcd for C 35 H 37 IrOP 2 Si: C, 55.64; H, 4.90. Found: C, 55,95; H, 5.10.
Method B From HIr(CO)(PPh 3 ) 3
To a solution of HIr(CO)(PPh 3 ) 3 (0.10 g, 0.11 mmol) in THF (10 mL) was added Ph 2 PCH 2 CH 2 SiMe 2 H (0.05 g, 0.18 mmol) dissolved in THF (8.5 mL). After stirring at ambient temperature for 60 min, during which time the reaction mixture became almost colorless, the THF was pumped away, and the residue was taken up in hexane (10 mL). Filtration to give a clear solution was followed by concentration to half volume and refrigeration (-20° C.). Colorless crystals of the product formed over 4 days (0.06 g, 0.08 mmol, 71%) and were shown to be identical with the material prepared by method A using IR and NMR spectroscopy.
(7) ##STR29##
This compound was shown to be the major product of reactions in refluxing THF between (a) complex (1a) and excess Ph 2 PCH 2 CH 2 SiMe 2 H (4 h) in the presence of NEt 3 and (b) complex (6) and excess Ph 2 PCH 2 CH 2 SiMe 2 H (12 h). It was identified on the basis of the IR spectrum and 1 H and 31 P NMR data, all of which were found to be identical with those of an authentic sample.
(8) ##STR30##
After complex (1a) was stirred with excess NaBr in acetone solution for 15 h, the solvent was removed; the remaining solid was then dissolved in the minimum of THF, and the resulting colorless solution was washed down a short column packed with alumina. Addition of hexane to the eluent precipitated the product (8) as a cream-colored powder. Anal. Calcd for C 35 H 36 BrIrOP 2 Si: C, 50.35; H, 4.35. Found: C, 50.69; H, 4.30.
(9) ##STR31##
Complex (1a) (0.15 g, 0.19 mmol) in THF (10 mL) was treated with a slight excess of MeMgI in the same solvent (10 mL). After 15 min, the reaction mixture was a very pale yellow color with a trace of solid present. After 10 h a white precipitate had separated leaving a yellow supernatant. Filtration through alumina followed by addition of hexane (10 mL) afforded a yellow solid, which was washed with hexane and then recrystallized (THF/hexane) to give the pure product (a). Anal. Calcd for C 35 H 36 IIrOP 2 Si: C, 47.67; H, 4.11; I, 14,39. Found: C, 47.48; H, 4.23; I, 14.10.
SYNTHESIS OF PHOSPHINOETHYLSILYL COMPLEXES
A. Five-coordinate compounds
(A1) ##STR32##
To a stirred solution in THF (10 mL) of [Rh(COD)Cl] 2 (0.020 g, 0.41 mmol) was added a solution of PPh 2 (CH 2 ) 2 SiMe 2 H (0.45 g, 1.70 mmol) also in THF (5 mL). After gas evolution had ceased the reaction mixture was stirred (30 min) then volatiles were removed by evacuation of 10 -2 mm Hg to leave a bright yellow oil. On addition of Et 2 O (2 mL) the product (A1) (0.45 g, 0.66 mmol, 81%) deposited as translucent yellow crystals. Anal. Calcd. for C 32 H 40 -CIP 2 RhSi 2 : C, 56.42; H, 5.91; Cl, 5.20. Found: C, 56.05; H, 5.86; Cl, 5.96%.
(A2) ##STR33##
Addition of Ph 2 P(CH 2 ) 2 SiMe 2 H (0.32 g, 1.20 mmol) in THF (5 mL) to a stirred solution of [Ir(COD)Cl] 2 (0.20 g, 0.30 mmol) also in THF (10 mL) resulted in gas evolution accompanied by a color-change from red to yellow. After stirring (30 min), the yellow mixture was filtered (alumina column, 5×3 cm 2 ) then solvent was pumped away affording an orange oil. Addition of Et 2 O (1 mL) gave chrome-yellow crystals of the product (A2) (0.33 g, 0.21 mmol, 35%). Anal. Calcd. for C 32 H 40 OClIrP 2 Si 2 : C, 49.88; H, 5.23. Found: C, 50.20; H, 5.55%.
(A3) ##STR34##
After stirring (24 h) complex (A1) (50 mg, 0.07 mmol) with excess NaBr in acetone (20 mL), removal of solvent was followed by extraction with benzene (20 mL). Filtration of the resulting solution, then evaporation of benzene afforded an oily residue which was dissolved in Et 2 O (1 mL); addition of hexane precipitated the product (A3), ca 90%, as a pale yellow powder. Anal. Calcd. for C 32 H 40 BrP 2 RhSi 2 : C, 52.97; H, 51.56. Found: C, 5.61, H, 5.50%.
(A4) ##STR35##
A procedure similar to that described above using NaI in acetone led to isolation of the yellow product (A4), ca 90% yield. Anal. Calcd. for C 32 2H 40 IP 2 RhSi 2 : C, 49.75; H, 5.22. Found C, 49.84; H, 5.39%.
(A5) ##STR36##
Compound (A2) (50 mg, 0.06 mmol) was stirred in acetone (20 mL) with excess NaBr for 24 h then solvent was removed to leave a whitish residue. Extraction by stirring (30 min) with benzene (30 mL) followed by filtration and concentration precipitated the yellow product (A5) in essentially quantitative yield. Anal. Calcd. for C 32 H 40 BrIrP 2 Si 2 : C, 47.16; H, 4.95. Found: C, 46.97; H, 4.95%.
(A6) ##STR37##
In a similar manner to that described above, treatment of compound (A2) with NaI in acetone yielded the product (A6) as a yellow powder. Anal. Calcd. for C 32 H 40 IIrP 2 Su 2 : C, 44.59; H, 4.68. Found: C, 44.73; H, 4.83%.
(B) Six-coordinate Compounds
(B7) ##STR38##
Drop by drop addition of a solution of Ph 2 P(CH 2 ) 2 SiMe 2 H (0.08 g, 0.30 mmol) in THF (5 mL) to a stirred solution in THF (10 mL) of [Ir(COD)Cl] 2 (0.10 g, 0.15 mmol) rapidly discharged the red color of the latter and after 5 min removal of solvent (B7) left a pale yellow oil. Addition of Et 2 O (1 mL) gave the product (0.12 g, 0.20 mmol, 67%) as ivory crystals. Anal. Calcd. for C 24 H 33 ClIrPSi: C, 47.319; H, 5.47; Cl, 5.83. Found: C, 47.53; H. 5.33; Cl, 6.27%.
(B8) ##STR39##
Diphos(bisdiphenylphosphinoethane (32 mg, 0.08 mmol) dissolved in THF (10 mL) was added dropwise to a stirred solution of complex (B7) (50 mg, 0.08 mmol) in THF (10 mL). After 5 min the mixture was filtered through an alumina plug (5×3 cm 2 ); removal of solvent gave a yellow oil which was redissolved in the minimum Et 2 O then hexane was added precipitating the pale yellow powdery product (B8) (35 mg, 0.04 mmol, 50%). Anal Calcd. for C 42 H 45 ClIrP 3 Si: C, 56.14; H, 5.05. Found: C, 55,98; H, 5.40%.
(B9) ##STR40##
Addition of dpm (bisdiphenylphosphinomethane: 30 mg, 0.08 mmol) in THF (5 mL) to a solution in THF (10 mL) of complex 7 (50 mg, 0.08 mmol) followed by stirring (5 min) then removal of solvent afforded a yellow oil. Redisollution in Et 2 O (2 mL) then addition of hexane (15 mL) precipitated the pale yellow product (B9) (59 mg, 0.07 mmol, 83%). Anal. Calcd. for C 41 C 43 ClIrP 3 Si: C, 55,68; H, 4.90. Found: C, 56.29; H, 5.34%.
(C) Six-coordinate Adducts of Complexes (A1) and (A2)
(C10) ##STR41##
On adding Bu t NC (ca 6 mg, 0.07 mmol) in THF (1 mL) to a solution of compound (A1) (50 mg, 0.07 mmol) in THF (2 mL) an immediate lightening in color was observed and removal of volatiles followed by addition Et 2 O (1 mL) yielded the cream microcrystalline product (C10) (51 mg, 0.066 mmol, 91%). Anal. Calcd. for C 37 H 49 ClNP 2 RhSi 2 : C, 58.15; H, 6.46; N, 1.83. Found: C, 57.28; H, 5.72; N, 1.79%.
(C11 and C12) ##STR42##
In parallel reactions to that used to obtain compound (C10), complex (A1) was treated with Me 3 CCH 2 CMe 2 NC or Me 2 CHNC to give cream-colored, crystalline products in 89, 86% yield respectively. Anal. Calcd. for C 41 H 57 ClNP 2 RhSi 2 : C, 60.03; H, 7.00; N, 1.71. Found: C, 59.94; H, 7.33; N, 1.71. Calcd. for C 36 G 47 ClNP 2 RhSi 2 : C, 57.63; H, 6.32; N, 1.87. Found: C, 57.58; H, 6.52; N, 1.84%.
(C13) ##STR43##
Carbon monoxide gas was bubbled through a solution of compound (A2) (50 mg, 0.06 mmol) in THF (5 mL) for 5 min during which time the initially bright yellow color was discharged. Addition of hexane (10 mL) to the resulting clear solution then concentration afforded the product (C13) (46 mg. 0.057 mmol, 88%) as a white powder. Anal. Calcd. for C 33 H 40 ClIrOP 2 Si 2 : C, 49.63; H, 5.05. Found: C, 49.77; H, 5.46%.
(C14) ##STR44##
Bubbling PF 3 into a solution of complex (A2) (50 mg, 0.06 mmol) in THF (5 mL) led to rapid decolorization and after 5 min the reaction mixture was treated in a manner similar to that described above to give the product (C14) (45 mg, 0.053 mmol, 81%) as a white solid. Anal. Calcd. for C 32 H 40 ClF 3 IrP 3 Si 2 : Cm, 44.77; H, 4.70. Found: C, 44.75; H, 5.08%.
(C15) ##STR45##
Dropwise addition of a solution of P(OMe) 3 (8 mg, 0.06 mmol) in THF (1 mL) to a stirred solution of complex (A2) (50 mg, 0.06 mmol) also in THF (5 mL) resulted in immediate decolorization. Removal of solvent in vacuo, then addition to the residual oil of Et 2 O (1 mL) afforded colorless crystals of the product (45 mg, 0.05 mmol, 78%). Anal. Calcd. for C 35 H 49 ClIrO 3 P 3 Si 2 : C, 46.99; H, 5.52. Found: C, 47.45; H, 5.46%.
(C16) ##STR46##
This adduct was isolated as a colorless, crystalline product (81% yield) by a method identical to that described for the trimethylphosphite analogue (C15). Anal. Calcd. for C 38 H 55 ClIrO 3 P 3 Si 2 : C, 48.73; H, 5.92. Found: C, 48.45; H, 5.93%.
(C17) ##STR47##
Complex (A2) (50 mg, 0.06 mmol) was dissolved in THF (6 mL) and Bu t NC (6 mg, 0.06 mmol) was added drop-by-drop with stirring. After 5 min solvent was removed from the colorless mixture leaving an oil to which was added Et 2 O (1 mL). The product (53 mg, 0.62 mmol, 95%) was obtained as colorless crystals. Anal. Calcd. for C 37 H 49 ClIrNP 2 Si 2 : C, 52.06; H, 5.79; N, 1.64. Found: C, 51.23; H, 5.61; N, 1.60%.
(C18 and (19) ##STR48##
These compounds were prepared by a similar procedure to that described above for complex (C17), by using Me 3 CCH 2 CMe 2 NC or Me 2 CHNC respectively. Yields of the colorless crystalline products were essentially quantitative. Anal. Calcd. for C 41 H 57 ClIrNP 2 Si 2 : C, 54.13; H, 6.32; N, 1.53. Found: C, 54.09; H, 6.39; N, 1.53. Calcd. for C 36 H 47 ClIrNP 2 Si 2 ; N, 1.53. Found: C, 54.09; H, 6,39; N, 1.53. Calcd. for C 36 H 47 ClIrNP 2 Si 2 : C, 51.50; H, 5.64; N, 1.67. Found; C, 50.37; H, 5.42; N, 1.60%.
(D) Related Six-coordinate Ir(III) Complexes
(D20) ##STR49##
Under an atmosphere of CO gas a solution of AgBF 4 (13 mg, 0.07 mmol) in acetone (5 mL) was added to a stirred solution of complex (A2) (50 mg, 0.06 mmol), also in acetone (10 mL). After 30 min the cloudy brown reaction-mixture was filtered through a 5×3 cm 2 column packed with CELITE, then solvent was removed leaving an oily residue which dissolved in the minimum of CH 2 Cl 2 . On addition of hexane the product (D20) (42 mg, 0.47 mmol, 73%) was precipitated as a white powder. Anal. Calcd. for C 34 H 40 BF 4 IrO 2 P 2 Si 2 : C, 46.52; H, 4.59. Found: C, 45.42; H, 4.14%.
(D21) ##STR50##
Method A
A suspension of the complex (C13) (52 mg, 0.065 mmol) in 100% EtOH (15 mL) was stirred for 24 h after addition of excess NaBH 4 in a further 10 mL EtOH. Replacement of EtOH by benzene (25 mL) was followed by stirring (30 min). Subsequent filtration and slow removal of solvent precipitated the product (D21) (37 mg, 0.48 mmol, 74%) as a cream-colored powder. Anal. Calcd. for C 33 H 41 IrOP 2 Si 2 : C, 51.88; H, 5.41. Found: C, 51.92; H, 5.54%.
Method B
To a stirred suspension of compound (A2) (50 mg, 0.06 mmol) in 100% EtOH (10 mL) was added excess NaBH 4 in 5 mL EtOH. After 60 min the EtOH was removed, THF (10 mL) was added, and the resulting mixture was filtered to give a pale brown solution into which was bubbled CO gas (5 min). Recovery from Et 2 O/hexane afforded a product identical (IR, NMR) to that obtained using Method A.
(D22) ##STR51##
Compound (A2) was dissolved in THF (5 mL) and excess LiAlH 4 in THF (1 mL) was added with stirring. After 5 min introduction of excess Bu t NC was followed by stirring for a further 20 h. Filtration through a plug of alumina then removal of solvent in vacuo gave a grayish residue which was extracted into Et 2 O (1 mL). Slow addition of hexane precipitated the white, powdery product (36 mg, 0.044 mmol, 67%). Anal. Calcd. for C 37 H 50 IrNP 2 Si 2 : C, 54.25; H, 6.15; N, 1.71. Found: C, 53.75; H, 6.07; N, 1.91%.
(E) Silyl-Iridium Complex
(E1) A chelate-stabilized silyl-iridium(I) complex was formed via reductive elimination from Ir(III) as follows:
UV irradiation was without effect on the cis-dihydridoiridium(III) complex ##STR52## In fact, prolonged photolysis (250 h, 450-W medium-pressure Hg lamp) in an evacuated quartz tube of a THF solution of compound 3, which results in extensive decomposition, is accompanied by conversion in low yield (<30%) to a product for which IR and 31 P NMR data 12 were compatible with formulation as an irridium(I) species ##STR53## Accordingly a similar reaction performed under an atmosphere of CO gas afforded compound 4 in over 80% yield in only 8 h. The same complex is recovered in ca. 80% yield after filtration and extraction into hexane following treatment of the precursor ##STR54## in THF solution with MeMgCl then CO gas. Careful recrystallization (ether/hexane mixture) provided colorless needless of compound 4 suitable for X-ray diffraction. The crystal structure determination confirms the geometry proposed on the basis of the spectral data (ORTEP drawing), ##STR55##
Selected bond distances and angles: Ir-Si, 2.454 (6); Ir-P(1), 2.342 (5); Ir-P(2), 2.371 (5); Ir-CO(1), 1.873 (19); Ir-CO (2), 1.795 (24) A. Si-Ir-P(1), 81.9 (2) o ; Si-Ir-P(2), 175.7(2) o ; P(1)-Ir-P(2), 101.7 (2) o ; Si-Ir-CO(1), 87.5 (8) o ; Si-Ir-CO(2), 84.1 (8) o ; P(1)-Ir-CO(1), 108.2 (7) o ; P(1)-Ir-CO(2), 119.6 (6) o ; P(2)-Ir-CO(1), 93.5 (8) o ; P(2)-Ir-Co(2), 92.0 (8) o .
Examples 1-16 below describe the synthesis of bis- and tris-(phosphenoalkyl)silanes as ligand precursors as the key to formation of the novel complexes which in turn are precursors in platinum chemistry for a novel series of catalytically-useful compounds.
The phosphinoalkylsilanes prepared were all synthesized and purified in a very similar fashion. The appropriate secondary phosphine R 2 PH (R=Ph, Cy) was reacted with the desired unsaturated silane giving photo-induced, free radical anti-Markovnikov addition of P-H across the unsaturated bond. Generally an excess of phosphine was used with a variety of solvents. The reagents were placed in a PYREX (trademark) vessel fitted with a high vacuum valve and generally freeze/thawed three times in liquid nitrogen. The reagents were then photolized using a 450 watt medium pressure mercury 5 to 25 cm from the lamp. Reaction times varied from two days to three months. Purification generally consisted of removal of solvent, if any, in vacuo followed by short path cold cup distillation of the residual secondary phosphine. This was usually achieved at 110° C. and 10 -2 torr. The products were, in all cases except one, clear colourless, very viscous liquids. Products were characterized by 1 H, 13 C, and 31 P NMR, infra red, mass spec, and C,H analysis.
EXAMPLE 1
4-methyl-1,7-bis(diphenylphosphino)-4-silaheptane, a bis(phosphinoalkyl)silane (1) ##STR56##
Diphenylphosphine, PPh 2 H, (3.58 g, 0.0192 mol) was syringed into a greaseless quartz tube. Diallylmethylsilane (1.21 g; 0.00958 mol) was then added with 10 mg of AIBN (azoisisobutyrl-nitrile). The reaction mixture was freeze-thawed three times and then irradiated at a distance of 5 cm from a medium pressure Mercury lamp for 100 hours. The reaction tube was air-cooled during the irradiation, preventing the temperature from rising above 40° C. The resulting product was a viscous, colourless liquid which had to be dissolved in THF to facilitate removal from the quartz tube. Removal of the solvent under vacuum was followed by cold cup distillation for 4 hours at 120° C. and 10 -2 mm Hg to remove the excess HPPh 2 . The product was obtained in approximately 100% yield based on diallymethylsilane and was characterized by 1 H, 13 C (Table 1), 31 P NMR spectroscopy, by I.R. and mass spectra, and elemental analysis. Anal. Calcd: C, 74.76; H 7.1. Found: C, 74.74; H, 7.16.
EXAMPLE 2
5-methyl-1,9-bis(diphenylphosphino)-5-silanoane (2) ##STR57##
The silane precursor (MeSi(H)(CH 2 CH 2 CH═CH 2 ) 2 was synthesized by standard Grignard methods starting from methyldichlorosilane and 4-bromobut-1-ene. This compound was photolyzed with diphenylphosphine PPh 2 H (3 mol equiv) in a fashion identical to that described in Example 1. The clear colorless viscous product was dissolved in methylene chloride (5 mL) to facilitate removal from the photolysis vessel. The CH 2 Cl 2 and excess PPh 2 H were removed as described above to yield the pure liquid product which was characterized by NMR spectroscopy and analysis.
EXAMPLE 3
3-methyl-1,5-bis(diphenylphosphino)-3-silapentane (3) ##STR58##
Methyldivinylsilane is required for this synthesis: this known silane was obtained by Grignard methods from vinyl bromide CH 2 ═CHBr and methyldichlorosilane. Following a procedure identical with that described in Examples 1 and 2 involving photolysis with PPh 2 H, the clear liquid product was prepared and purified.
EXAMPLE 4
1,5-bis-(dicyclohexylphosphino)-3-methyl-3-silapentane (4)
Cy 2 PCH 2 CH 2 Si(Me)HCH 2 CH 2 PCy 2
Divinylmethylsilane (approximately 8×10 -3 mol in THF/ether) and dicyclo-hexylphosphine (5.0 mL; 4.5 g; 0.023 mol) were irradiated approximately 25 cm from the UV lamp for 90 days. Removal of the solvent and dicyclohexylphosphine yielded 2.5 g of the colourless product.
EXAMPLE 5
1,5-bis(diphenylphosphino)-3-phenyl-3-silapentane (5)
Ph 2 PCH 2 CH 2 Si(Ph)HCH 2 CH 2 PPh 2
Divinylphenylsilane (1.6 mL; 1.43 g; 8.94×10 -3 mol) was placed in a PYREX tube and ether (2 mL) added. Diphenylphosphine [Ph 2 PH] (3.26 mL; 3.49 g; 1.88×10 -2 mol) was added and the sample irradiated approximately 25 cm from the UV lamp for 72 hours. Removal of solvent and diphenylphosphine yielded 4.68 g of a clear colourless, very viscous, liquid. Yield=98.3%.
EXAMPLE 6
1-(diphenylphosphino)-3-phenyl-3-silapent-4-ene (6)
Ph 2 PCH 2 CH 2 Si(Ph)HCH═CH 2
Divinylphenylsilane (1.789 g; 1.12×10 -2 mol) and ether (20 mL) was placed in a PYREX tube with diphenylphosphine (1.96 mL; 2.10 g; 1.12×10 -2 mol). The solution was irradiated for 50 hours approximately 25 cm from the UV lamp. Vacuum distillation at approximately 10 -2 torr yielded unreacted divinylphenylsilane at 80° C. and the desired product at 200° C. 1.04 g of a clear, colourless liquid was obtained. Yield=27.5%.
EXAMPLE 7
1-(Dicyclohexylphosphino)-5-(diphenylphosphino)-3-phenyl-silapentane (7)
Cy 2 CH 2 CH 2 Si(Ph)HCH 2 CH 2 PPh 2
1-(diphenylphosphino)-3-phenyl-3-silapent-4-ene (1.0 g; 2.95×10 -3 mol) was placed in a PYREX tube and ether (2 mL) and dicyclohexyphosphine (0.61 g; 3.24×10 -3 mol) added. The solution was irradiated for 200 hours. Removal of solvent and unreacted starting materials yielded 1.45 g of a clear, colourless product. Yield=93.5%.
EXAMPLE 8
1,5-bis(dicyclohexylphosphino)-3-phenyl-3-silapentane (8)
Cy 2 CH 2 CH 2 Si(Ph)HCH 2 CH 2 PCy 2
Divinylphenylsilane (1.5 mL; 1.34 g; 8.38×10 -3 mol), ether (2 mL) and dicylohexylphosphine (4 mL; 3.62 g; 1.82×10 -2 mol) were irradiated for 100 hours approximately 25 cm from the UV lamp. Removal of solvent and dicyclohexylphosphine yielded 4.35 g of a clear colourless, very viscous liquid. Yield=93.1%.
EXAMPLE 9
tri(-2-diphenylphosphinoethyl)silane (9)
(Ph 2 PCH 2 CH 2 ) 3 SiH
Trivinylsilane (approximately 0.4 g in 4 mL THF/ether) and diphenylphosphine (2.0 mL; 2.14 g; 1.11×1- -2 mol) was irradiated for 70 hours approximately 25 cm from the UV lamp. Removal of the solvent and diphenylphosphine yielded 2.2 g of product. The product was initially obtained as a liquid, but upon manipulation formed a sticky white solid.
EXAMPLE 10
tris(-2-dicyclohexylphosphinoethyl)silane (10)
Cy 2 PCH 2 CH 2 ) 3 SiH
Trivinylsilane (approximately 0.5 g in 20 mL THF/ether) and dicyclohexylphosphine (4.0 mL; 3.57 g; 1.80×10 -2 mol) was irradiated for 1440 hours approximately 25 cm from the UV lamp. Removal of the solvent and excess dicyclohexylphosphine yielded 2.5 g of a slightly yellow, very sticky liquid.
EXAMPLE 11
1,7-bis(dicyclohexylphosphino)-4-methyl-4-silaheptane (11)
Cy 2 PCH 2 CH 2 CH 2 Si(CH 3 )HCH 2 CH 2 CH 2 PCy 2
Diallylmethylsilane (1.0 mL; 0.77 g; 6.02×10 -3 mol) and dicyclohexylphosphine (2.8 mL; 2.54 g; 1.28×10 -2 mol) was irradiated in a PYREX tube for 300 hours approximately 6 cm from the UV lamp with air cooling on the sample tube. Removal of dicyclohexylphosphine yielded 2.86 g of a clear, colourless, very viscous liquid. Yield=91.2%.
EXAMPLE 12
1-(diphenylphosphino)-4-methyl-4-silahept-6-ene (12)
Ph 2 PCH 2 CH 2 CH 2 Si(CH 3 )HCH 2 CH═CH 2
Diallylmethylsilane (1.008 g; 7.98×10 -3 mol), ether (10 mL) and diphenylphosphine (1.40 mL; 1.50 g; 7.98×10 -3 mol) was irradiated approximately 25 cm from the UV lamp for 400 hours. The product was obtained via short path vacuum distillation at 220° C. and 10 -2 torr. 0.5 g of a clear, colourless liquid was obtained. Yield=19.9%.
EXAMPLE 13
1-(dicyclohexylphosphino)-7-(diphenylphosphino)-4-methyl-4-silaheptane (13)
Cy 2 PCH 2 CH 2 CH 2 Si(CH 3 )HCH 2 CH 2 CH 2 PPh 2
1-(diphenylphosphino)-4-methyl-4-silahept-6-ene (0.45 g; 1.43×10 -3 mol), benzene (7 mL) and dicyclohexylphosphine (0.70 g; 3.5×10 -3 mol) was irradiated for 3000 hours.
EXAMPLE 14
1,7-bis(diphenylphosphino)-4-phenyl-4-silaheptane (14)
Ph 2 PCH 2 CH 2 CH 2 Si(Ph)HCH 2 CH 2 CH 2 PPh 2
Diallylphenylsilane (1.50 mL; 1.316 g; 6.987×10 -3 mol), ether (2 mL) and diphenylphosphine (3.0 ml; 3.25 g; 1.75×10 -2 mol) was irradiated approximately 25 cm from the UV lamp for 360 hours. Removal of solvent and diphenylphosphine yielded 3.28 g of a clear, colourless, very viscous liquid. Yield=83.7%.
EXAMPLE 15
1,7-bis(dicyclohexylphosphino)-4-phenyl-4-silaheptane (15)
Cy 2 PCH 2 CH 2 CH 2 Si(Ph)HCH 2 CH 2 CH 2 PCy 2
Diallylphenylsilane (0.854 g; 4.53×10 -3 mol) and dicyclohexylphosphine (2.10 ml; 1.89 g; 9.52×10 -3 mol) were placed in a quartz tube and irradiated approximately 25 cm from the UV lamp for 1000 hours. During the reaction the solution darkened and some brown solid formed. Filtration and removal of the dicyclohexylphosphine resulted in a mixture consisting mostly of the product, but containing impurities which could not be removed.
EXAMPLE 16
tris(-3-diphenylphosphinopropyl)silane (16)
(Ph 2 PCH 2 CH 2 CH 2 ) 3 SiH
Triallylsilane (1.02 g;p 6.66×10 -3 mol), hexanes (10 mL) and diphenylphosphine (4.7 mL; 5.02 g; 2.66×10 -2 mol) were placed in a PYREX tube and irradiated for 360 hours approximately 25 cm from the UV lamp. Removal of solvent and diphenylphosphine yielded 4.2 g of a cloudy, white, very viscous liquid. Yield=87.9%.
Examples 17 and 18 describe the synthesis of representative bis(phosphinoalkyl)silyl complexes of Rh(III) and Ir(III).
EXAMPLE 17 ##STR59##
The bis(phosphinopropyl)silane prepared as described in Example 1 (0.188 g, 0.38 mmol) was weighed. Cloro(cyclo-octa-1,5-diene)iridium dimer, (IR(COD)Cl) 2 (0.1265 g; 0.1883 mmol) was weighed into a Schlenk tube which was subsequently evacuated then purged with N 2 gas, and dissolved in THF (15 ml). The bis(phosphinoalkyl)silane solution was added to the stirring orange solution in THF (2×5 mol) causing an immediate lightening to a yellow color. The resultant solution was stirred for 51/2 hours and pumped on overnight yielding a yellow solid which was scraped to give a powder. Green-yellow crystals were obtained from an ether/hexane mixture in the freezer. 1 H, 13 C, 31 P NMR spectroscopy, by I.R. spectroscopy and elemental analysis. Anal. Calcd: C, 51.26; H, 4.99. Found: C, 51.46; H, 4.99.
EXAMPLE 17A
Structural Characterization of the bis(phosphinoalkyl)silyl-iridium(III) complex obtained as described in Example 17
Crystals of the complex suitable for single-crystal X-ray diffraction were grown from cold ether/hexane solutions. Crystal data: M 1 =726.3; space group P 21 /n; Å, a=11.0387 (10) Å,b 24.3222 (12) Å,c=11.3177 (10); V (A3)=3010.56 (10); Z=4; D calcd =1.60 g cm 3 ; MoK α radiation=44.91 radiation, μ=0.71069 cm -1 ; 3268 observed reflections refined to a conventional R=0.0375 (R w =0.0449).
EXAMPLE 18 ##STR60##
Following a procedure similar to that described in Example 4 using chloro(cycloocta-1,5-diene)rhodium dimer as the organometallic precursor, the rhodium (III) analogue of the iridium(III) structurally characterized (Example 5) was prepared and identified by 1 H and 31 P NMR spectroscopy and IR spectroscopy.
Examples 19-27 describe the synthesis of representative bis(phosphinoalkyl)silyl complexes of Pt(II).
Metal complexes were synthesized by the reaction of stoichiometric quantity of the respective ligand precursor with a suitable metal complex. The metal reagents were synthesized according to literature methods. Due to the very viscous and air-sensitive nature of the ligand precursors, special techniques were employed to weigh small accurate quantities. Typically, a glass weighing bottle fitted with a ground glass joint and containing a small glass "spoon" was placed in a wide mouth Schlenk tube (B 34), evacuated and let down to an N 2 atmosphere. The stopper was then inserted and the weighing bottle weighed. The weighing bottle was then placed in the Schlenk tube, and the glass "spoon" removed with a pair of long forceps. The "spoon" was then dipped in the viscous ligand precursor to collect some of the material. After rapid transfer of the spoon back to the weighing bottle, the sample was evacuated, let down to an N 2 atmosphere, and weighted. One such transfer would generally consist of approximately 50 mg of compound. More compound could be obtained by repeated transfers or by the use of more than one "spoon". The above technique can be used to obtain small quantities of viscous, air-sensitive materials of an accurate weight. Once the mass of the ligand precursor was known, the stoichiometric amount of the reagent metal complex was calculated and weighed out. This was then placed in a Schlenk tube, evacuated, let down to an N 2 atmosphere, and dissolved in the solvent of choice. The ligand precursor, in the glass weighing bottle, was then dissolved in the same solvent and transferred to the stirring solution of the metal complex. The reaction mixture was then stirred for varying lengths of time after which the solvent was removed in vacuo. A variety of purification techniques were then employed depending on the sample in question.
EXAMPLE 19 ##STR61##
This bis(phosphinopropyl)silane obtained by the procedure described in Example 1 (0.2426 g; 0.487 mmol) was transferred from a weighing bottle under N 2 into a Schlenk tube with the addition of benzene (4×5 mL). Distilled NEt 3 (2.4 mL; 0.016 mol) was added to this solution. Dichloro(cycloocta-1,5-diene)platinum (II), (COD)PtCl 2 (0.1825 g; 0.0487 mmol) was placed in a Schlenk tube with benzene (15 mL). The white solid did not dissolve. The ligand/NEt 3 solution was added to the stirring (COD)PtCl 2 suspension over 20 seconds causing a yellowing and the formation of a very fine precipitate. The solvent was pumped off after 15 min yielding a bubbly yellow oil/solid. Benzene (30 mL) was added and the resulting yellow solution was filtered through 5 mm of FLORISIL on a glass frit. Pumping away of volatiles left a solid reside which was washed with hexane (2×5 mL) to yield pure product in greater than 95% yield. The product was characterized by 1 H, 13 C, 31 P an d 195 Pt NMR spectroscopy, by I.R. and by mass spectra, and by elemental analysis. Anal. Calcd; C, 51.13; H 4.85. Found: C, 50.99; H, 4.81.
EXAMPLE 19A
Structural Characterization of the bis(phosphinoalkyl)silyl-platinum(II) complex obtained as described in Example 19
Crystals of the complex were obtained from a saturated ether solution. Crystal data: M 1 =728.2; space group I12/al Å, a=21.5818 (20) Å, b=12.7136 (15) Å, c=22,1190 (20); V (A3)=6050.36 (20); Z=8; D calcd =1.58 g cm 3 ; MoK α radiation =48.51; μ=0.71069; 2735 observed reflections refined to a conventional R=0.0876 (R 2 =0.841).
EXAMPLE 20 ##STR62##
The product obtained as described in Example 6 (0.073 g; 0.10 mmol) was dissolved in benzene (10 mL). Anhydrous SnCl 2 (0.025 g; 0.13 mmol) was added but did not appear to dissolve and the reaction mixture remained colorless. After 15 min THF (2 mL) was added, at which point the SnCl 2 dissolved and a fine orange-yellow suspension began to form. Subsequent removal of the solvent mixture afforded an orange product which was characterized by using 31 P NMR spectroscopy.
EXAMPLE 21 ##STR63##
Addition of benzene saturated with HCl gas (1 mol equiv vs Pt complex) to the product obtained as described in Example 6 also dissolved in benzene resulted in an initial color change to pale yellow followed by formation of a colorless solution. Evaporation of benzene afforded a white solid product which has characterized by NMR and IR spectroscopy.
EXAMPLE 22
{1,5-bis(diphenylphosphino)-3-methyl-3-silylpentane}platinum(II)chloride (22)
[(PPh 2 CH 2 CH 2 Si(CH 3 )CH 2 CH 2 PPh 2 )PtCl]
(COD)PtCl 2 (0.0786 g; 2.098×10 -4 mol) and PPh 2 CH 2 CH 2 Si(CH 3 )HCH 2 CH 2 PPh 2 (0.0987 g; 2.098×10 -4 mol) were mixed in THF (2×6 mL) with NEt 3 (approximately 1 mL) present. Removal of solvent in vacuo followed by washing with THF (3×5 mL) yielded 0.135 g. of a white solid, insoluble in all solvents investigated. Yield=92.0%.
EXAMPLE 23
{1,5-bis(dicyclohexylphosphino)-3-methyl-3-silylpentane}platinum(II)chloride (23)
[(Cy 2 PCH 2 CH 2 Si(CH 3 )CH 2 CH 2 PCy 2 )PtCl]
(COD)PtCl 2 (0.1535 g; 4.098×10 -4 mol) and Cy 2 PCH 2 CH 2 Si(CH 3 )HCH 2 CH 2 PCy 2 (0.2027 g; 4.098×10 -4 mol) were combined in THF (2×10 mL) with NEt 3 (approximately 1 mL). Removal of the solvent in vacuo followed by extraction with benzene (3×5 mL) yielded 0.250 g. of a white solid. Yield=84.3%.
EXAMPLE 24
{1,5-bis(dicyclohexylphosphino)-3-phenyl-3-silylpentane}platinum(II)chloride (24)
[(Cy 2 CH 2 CH 2 Si(Ph)CH 2 CH 2 PCy 2 )PtCl]
(COD)PtCl 2 (0.104 g; 2.77×10 -3 mol) and Cy 2 PCH 2 CH 2 Si(Ph)CH 2 CH 2 PCy 2 (0.154 g; 2.77×10 -4 mol) were combined in benzene (2×10 mL) with NeT 3 (approximately 1 mL). Removal of the solvent in vacuo followed by extraction with benzene (2×10 mL) yielded 0.075 g. of a white solid. Yield=34.5%.
EXAMPLE 25
{1-(dicyclohexylphosphino)-5-(diphenylphosphino)-3-phenyl-3-silylpentane}platinum(II)chloride (25)
[(Cy 2 CH 2 CH 2 Si(Ph)CH 2 CH 2 PPh 2 )PtCl]
(COD)PtCl 2 (0.0782 g; 2.09×10 -4 mol) and Cy 2 PCH 2 CH 2 Si(Ph)HCH 2 CH 2 PPh 2 (0.114 g; 2.09×10 -4 mol) were combined in benzene (2×10 mL) with NEt 3 (approximately 1 mL). Removal of the solvent in vacuo yielded 0.1220 g. of an off-white solid. Yield=75.4%
EXAMPLE 26
{1,7-bis(diphenylphosphino)-4-phenyl-4-silylpentane}platinum(II)chloride (26)
[(Ph 2 PCH 2 CH 2 CH 2 Si(Ph)CH 2 CH 2 PPh 2 )PtCl]
(COD)PtCl 2 (0.199 g; 5.33×10 -4 mol) and Ph 2 PCH 2 CH 2 CH 2 CH 2 Si(Ph)HCH 2 CH 2 PPh 2 (0.299 g; 5.33×10 -4 mol) were combined in benzene (2×10 mL) with NEt 3 (approximately 1 mL). Removal of the solvent in vacuo followed by extraction and filtration with benzene yielded 0.305 g. of a cream coloured solid. Yield=72.4%.
EXAMPLE 27
{1,7-bis(dicyclohexylphosphino)-4-methyl-4-silylheptane}platinum(II)chloride (27)
[(Cy 2 PCH 2 CH 2 CH 2 Si(CH 3 )CH 2 CH 2 CH 2 PCy 2 )PtCl]
(COD)PtCl 2 (0.1327 g; 3.541×10 -4 mol) and Cy 2 PCH 2 CH 2 CH 2 Si(CH 3 )CH 2 CH 3 CH 2 PCy 2 (0.1851 g; 3.541×10 -4 mol) were combined in benzene (2×10 mL) with NEt 3 (approximately 1 mL). Removal of the solvent in vacuo followed by extraction and filtration with benzene yielded 0.2014 g. of a cream coloured solid. Yield=75.5%.
Examples 28-34 describe the synthesis of representative bis- and tris(phosphinoalkyl)silyl complexes of Rh(I), Rh(III), and Ir(III).
EXAMPLE 28
{1,7-bis(diphenylphosphino)-4-methyl-4-silylheptane}hydridocarbonyliridium(III)chloride (28)
[(PPh 2 CH 2 CH 2 CH 2 Si(CH 3 )CH 2 CH 2 CH 2 PPh 2 )IR(H)(CO)(Cl)]
(PPh 3 ) 2 Ir(CO)(Cl) (0.5656 g; 7.251×10 -4 mol) and PPh 2 CH 2 CH 2 CH 2 Si(CH 3 )HCH 2 CH 2 CH 2 PPh 2 (0.3611 g; 7.25×10 -4 mol) were combined in CH 2 Cl 2 (2×10 mL). The initially yellow suspension gave away to a colourless solution. Removal of the solvent in vacuo yielded a white sticky solid which was washed with ether (3×5 mL). Removal of the residual ether in vacuo yielded 0.361 g of a fine white powder. Yield=66.0%.
EXAMPLE 29
{1,7-bis(diphenylphosphino)-4-methyl-4-silylheptane}hydridotriclorostanyliridium(III)carbonyl (29)
[(PPh 2 CH 2 CH 2 CH 2 Si(CH 3 )CH 2 CH 2 CH 2 PPh 2 )Ir(SnCl 3 )H(CO)]
I(PPh 2 )CH 2 CH 2 CH 2 Si(CH 3 )CH 2 CH 2 PPh 2 )Ir(H)(CO)(Cl)](0.080 g; 1.06×10 -4 mol) and SnCl 2 (0.0201 g; 1.06×10 -4 mol) were combined in THF (10 mL) and stirred for 1 hour. Removal of solvent in vacuo yielded 0.100 g of a fine white solid. Yield=99.9%.
EXAMPLE 30
{tris(-2-diphenylphosphinoethyl)silyl}iridium(III) hydridochloride (30)
[((PPH 2 CH 2 CH 2 ) 3 Si)IR(H)(Cl)]
[(COD)IrCl] 2 (0.1264 g; 3.764×10 -4 mol) was added to a stirring solution of (PPh 2 CH 2 CH 2 CH 2 ) 3 SiH (0.2517 g; 3.76×10 -4 mol) in THF (15 mL). Removal of the solvent in vacuo from the yellow solution yielded 0.3112 g of a brownish solid. Yield=92.2%.
EXAMPLE 31
{1,7-bis(diphenylphosphino)-4-methyl-4-silylheptane}hydridocarbonyliridium(III)chloride (31)
[(PPh 2 CH 2 CH 2 CH 2 Si(CH) 3 CH 2 CH 2 CH 2 PPh 2 )IR(H)(CO)(Cl)]
[(PPh 2 CH 2 CH 2 CH 2 Si(CH 3 )HCH 2 CH 2 CH 2 PPh 2 (0.0781 g; 1.586×10 -4 mol) in benzene (5 mL) was added to a stirring suspension of [(PPh 3 ) 2 Rh(CO)(Cl)](0.1083 g; 1.586×10 -4 mol) in benzene (3 mL). The solid dissolved immediately upon the above addition yielding a light yellow solution. Removal of the solvent in vacuo yielded 0.095 g of a light yellow solid. Yield=91.2%.
EXAMPLE 32
{tris(-2-diphenylphosphinoethyl)silyl}rhodium(III) hydridochloride (32)
[((PPh 2 CH 2 CH 2 ) 3 Si)Rh(H)(Cl)]
(1) [(COD)Rh(Cl)] 2 (0.1439 g; 2.94×10 -4 mol) was dissolved in THF (10 mL) and a solution of (PPh 2 CH 2 CH 2 ) 3 SiH (0.3912 g; 5.849×10 -4 mol) in THF (10 mL) added. After approximately 1 min., a flocculent yellow precipitate formed. Removal of the solvent in vacuo yielded 0.4349 g of a yellow/brown solid. Yield=92.1%.
(2) [(PPh 3 ) 2 Rh(CO)(Cl)](0.1014 g; 1.454×10 -4 mol) was dissolved in THF (10 mL) and (PPh 2 CH 2 CH 2 )SiH (0.0982 g; 1.464×10 -4 mol) added in THF (5 mL). Removal of the solvent in vacuo followed by washing with ether (3×5 mL) yielded 0.085 g of a yellow/brown solid. Yield=71.8%.
EXAMPLE 33
{tris(-2-diphenylphosphinoethyl)silyl}rhodium(I)carbonyl (33)
[((PPh 2 CH 2 CH 2 ) 3 Si)Rh(CO)
(1) (PPh 2 CH 2 CH 2 ) 3 SiH (0.106 g; 1.59×10 -4 mol) and [(PPh 3 ) 3 Rh(H)(CO)](0.145 g; 1.59×10 -4 mol) were added together and THF (10 mL) added. Immediate gas evolution was evident (H 2 ). Removal of the solvent in vacuo from the yellow solution, followed by washing with ether (3×5 mL) yielded 0.065 g of a bright yellow micro-crystalline solid. Yield=51.4%.
(2) [((PPh 2 CH 2 CH 2 ) 3 Si)Rh(H)(Cl)](0.2000 g; 2.47×10 -4 mol) was dissolved in THF (20 mL) and placed under CO at 1 atm. for 5 min. Excess LiAlH 4 was added and the grey suspension filtered through an alumina plug. Removal of the solvent in vacuo yielded 0.095 g of a fine yellow solid. Yield=48.0%.
EXAMPLE 34
{tris(-2-diphenylphosphinoethyl)silyl}rhodium(I)carbonyl triphenylphosphine (34)
[((PPh 2 CH 2 CH 2 ) 3 Si)Rh(PPh 3 )]
(PPh 2 CH 2 CH 2 ) 3 SiH (0.0876 g; 1.23×10 -4 mol) was dissolved in THF (5 mL) and [PPh 3 ) 4 Rh(H)] (0.1422 g; 1.234×10 -4 mol) added. Removal of the solvent in vacuo followed by washing with ether (2×5 mL) yielded 0.075 g of a black/green solid. It was not possible to remove all of the excess triphenylphosphine from the sample. Yield=56.5%.
Examples I, II and III below describe the activity of the complexes described above as hydroformylation catalysts. The procedure was carried out using standardized experimental conditions. A Parr Model 4561 300 mL stainless steel pressure reactor (`bomb`) was used in all cases.
The following procedure should be used for screening compounds for hydroformylation catalysts.
1. Bomb conditions should be standardised at 70° C. and 1000 p.s.i. total pressure with a 50:50 mix CO and H 2 for 16 hrs. A TEFLON liner should not be used since the temperature fluctuations are too great. A small glass flask should be used and the temperature should be allowed to rise slowly. The bomb must be flushed at least three times with CO before charging it finally. The pressure must be lowered slowly on completion to avoid flash vapourisation.
2. The catalyst-to-substrate (1-hexene) ratio should be kept roughly the same for all runs, 5×10 -5 mole catalyst should be used in 3 mis 1-hexene and 4 mls benzene.
3. The pressure should be taken at regular intervals since this gives a good indication of the rate. If the pressure drop is very quick then further experiments should be carried out at lower temperature and pressures.
4. Products from the bomb can be characterised by G.C. and G.C./M.S. (if required). Since hydrogenation may take place as well, it is necessary to set the G.C. condition to achieved good separation of hexane from hexene. For A 0.5 ul injection the following conditions will achieve adequate separation.
TEMP. 26° C. for 3 mins. then 15° C./min to 240° C. It may be necessary to adjust the attenuation for satisfactory results. Under these conditions, the hexane and hexene will come off after 2.5 mins with 0.1 min separation (both peaks will have to be on scale); the aldehydes will come off much later (6-8 mins). With these starting materials, the two major aldehydes should be 2-methylhexanal and heptanal, the latter having the longest retention time. Retention times can e checked by adding a small quantity of the pure material to peak enhance the chromatogram.
5. It is important that from time to time the state of the glass liner in the injector port must be checked. If it has any metal deposits at all the glass must be cleaned and replaced. The bomb must be cleaned thoroughly between runs.
DESCRIPTION OF USE OF THE INVENTION
EXAMPLE I
Process for the Catalytic Hydroformylation of Hex-1-ene by Various Phosphinoalkylsilyl Complexes
The bomb was charged with 1-hexene (3 mL, 24 mmol), benzene (4 mL, 45 mmol) and catalyst (5×10 2 mmol). After repeated flushing with CO, the bomb was pressured to 1000 p.s.i. with a 1:1 mixture of CO/H 2 . The temperature of the reactor was raised slowly to 70° C. and maintained for 16 hours then allowed to cool. The gases were vented off slowly and the products analysed by GLC and mass spectrometry. The results are summarized below:
__________________________________________________________________________ Yield (%) Selectivity RatioCatalyst (including hexane) to aldehydes straight:branched__________________________________________________________________________ ##STR64## 66 87.2 2.56:1 ##STR65## 100 27 1.16:1 ##STR66## No catalytic Activity ##STR67## 18.2 73.8 2.9:1 ##STR68## 7.03 30.9 2.9:1 ##STR69## 22.5 74.4 2.8:1 ##STR70## 100 100 1.09:1__________________________________________________________________________
EXAMPLE II
Process for Catalytic Hydroformylation of Hex-1-ene by Bis(phosphinoalkyl)silyl Complexes of platinum(II)
(a) The product obtained as described in Example 6 shows no detectable catalytic activity (hydrogenation or hydroformylation) under the standard test-condition detailed above.
(b) The product obtained as described in Example 6 (22 mg) with SnCl 2 (2 mol equiv., 11.4 mg) was used as catalyst for hex-1-ene hydroformylation under conditions similar to those already specified above. Using hex-1-ene (3 mL) and benzene (4 mL) with CO (400 psi) and H 2 (400 psi) with heating to 75° C. for 15 h conversion to C 7 aldehydes was 29% with 93% n-heptaldehyde (13.3:1 n:islo).
Repeat runs (3) set up in the same way yielded highly consistent results (93%, 93%, 94% selectivity). At the end of these experiments the solution recovered from the bomb was clear orange becoming cloudy over ca 1 h at ambient.
(c) The product obtained as described in Example 8 (23 mg) with SnCl 2 (1 mol equiv., 5.0 mg) was used as catalyst in an experiment set up as in Example 12(b). At the end of the run conversion was 34.7% with 92% selectivity (11.5:1 ratio).
As described above, the activity of a range of complexes as catalysis in the hydroformylation of hex-1-ene to heptaldehydes has been investigated. Typical conditions are 70°-100° C. using total 1000 psi of equimolar CO/H 2 mixtures. Product mixtures were analyzed by GLC. Products were identified using GLC retention time, mass spectrometry, and 1 H NMR spectroscopy.
The significant catalytic properties of the complexes of this invention are as follows:
(1) Olefin hydroformylation is strongly preferred over hydrogenation in most cases: this is a significant observation in view of its commercial desirability.
(2) In terms of rate, most of the complexes show moderate to high activity.
(3) In terms of selectivity the novel complexes of aspects of this invention show very high straight-chain: branched ratios.
The phosphinoalkylsilyl complexes of Rh, Ir, and Pt are catalysts for hydroformylation of hex-1-ene to heptaldehydes. Selectivity vs hydrogenation and overall conversion rates are generally good. Selectivity n vs branched heptaldehyde product is generally high.
The Pt complex ##STR71## is inactive for hex-1-ene hydroformylation (or hydrogenation) under the conditions tested, but in the presence of stannous chloride SnCl 2 as promoter it is efficient hydroformylation catalyst with no evidence for competing hydrogenation and with a very high (ca 20:1) selectivity for n vs branched heptaldehyde.
EXAMPLE III
Process for Catalytic Hydroformylation of Oct-1-ene by Tris(phosphinoalkyl)silyl Complex of rhodium(I)
The product obtained as described in Example 33 above (25.7 mg; 3.22×10 -5 mol) was used as catalyst for oct-1-ene hydroformylation under conditions similar to those already specified above.
(a) Using oct-1-ene (3 mL) and toluene (4 mL) with CO (380 psig) and H 2 (760 psig) with heating to 70° C. for 16 hours, conversion C 9 aldehydes was 100% with 69.5% n-nonaldehyde (2.31:1 n-iso)
(b) Using oct-1-ene (3 mL) and toluene (4 mL) with CO (200 psig) and H 2 (250 psig) with heating to 70° C. for 14.5 hours conversion to C 9 aldehydes was 98.6% with 68.3% n-nonaldehyde. (2.13:1 n:iso) (approx. 1 turnover/min.)
At the end of the examples the solution was clear orange in colour.
CONCLUSION
From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions. Consequently, such changes and modifications are properly, equitably, and "intended" to be, within the full range of equivalence of the following claims. | A novel hydroformylation process for the conversion of olefins having up to about 20 carbon atoms to their corresponding aldehydes is provided herein involving the use of catalysts comprising chelates in which a ligand is chelated at a metal center to produce at least one heterocyclic ring with the central metal atom as part of the ring, i.e., platinum-group metal phosphinoalkylsilyl complexes with bis- or tris(phosphinoalkyl)silyl. Novel catalysts are also provided which are platinum-group metal complexes with bis- or tris(phosphinoalkyl)silyl ligands, which are synthesized by using novel bis(phosphinoalkyl)silanes or tris(phosphinoalkyl)silanes. | 2 |
BACKGROUND OF THE INVENTION
[0001] (1) Field of Invention
[0002] The present invention relates to packaging for a writing instrument and, more particularly, to an interactive package for a writing instrument that allows a user to grasp the writing instrument without removing it from the packaging.
[0003] (2) Description of Related Art
[0004] Packaging for a writing instrument is typically a box-shaped container holding the writing instrument therein. In some cases, the container is formed of a clear material, allowing a user (e.g., potential customer) to view the contents of the container. In such containers, should the user decide to touch or feel the writing instrument, the user is required to open and remove the writing instrument from the container.
[0005] For retailers, opened containers pose a problem as the opened container may exhibit wear from being opened. Additionally, a packaging container exhibiting wear often dissuades another customer from purchasing that particular product, resulting in discounted prices and/or unsold products.
[0006] Thus, a continuing need exists for an interactive package for a writing instrument that allows a user to touch and feel the writing instrument without removing the writing instrument from the packaging.
SUMMARY OF INVENTION
[0007] The present invention is related to an interactive package for a writing instrument. The interactive package comprises a back support with a first end and a second end. An outer shell is connected with the back support to define a compartment in combination with the back support. A mount is positioned in the compartment for supporting a writing instrument. The mount comprises a first portion and a second portion, and the writing instrument comprises a writing end and a non-writing end. The first portion of the mount is formed to mount the non-writing end of the writing instrument and the second portion of the mount is formed to mount the writing end of the writing instrument. The outer shell encloses the mount and supported writing instrument to securely protect the writing instrument. Additionally, the outer shell includes an opening configuration sized and shaped to permit a user's fingers to enter the compartment and grasp the writing instrument.
[0008] In another aspect, the opening configuration includes two openings sized and shaped to permit a finger and a thumb of a user to enter and grasp the writing instrument without otherwise substantially touching the outer shell, mount, or back support.
[0009] In yet another aspect, the back support further comprises a hanging mechanism connected with the first end for hanging the package on a shelf.
[0010] Additionally, the back support is formed of a material selected from a group consisting of plastic, paper, or cardboard.
[0011] Furthermore, the back support is made from a clear plastic.
[0012] In yet another aspect, the mount is formed to frictionally fit between the back support and the outer shell.
[0013] Additionally, the mount is formed in a triangular shape.
[0014] In another aspect, the first portion of the mount and second portion of the mount are formed separately, and wherein the first portion of the mount is connected with the first end of the back support, and wherein the second portion of the mount is connected with the second end of the back support.
[0015] In yet another aspect, the first portion of the mount further comprises an indentation to frictionally fit the non-writing end of the writing instrument, and wherein the second portion of the mount further comprises an indentation to frictionally fit the writing end of the writing instrument, such that the writing instrument is mounted between the two indentations.
[0016] In another aspect, the indentation of the first portion and the indentation of the second portion of the mount are centered between the back support and the outer shell, such that when the writing instrument is mounted it appears to float within the package.
[0017] In another aspect, the mount formed of a material selected from a group consisting of plastic, paper, or cardboard.
[0018] In yet another aspect, the back support is made from a clear plastic.
[0019] In another aspect, the outer shell is formed to frictionally fit the mount.
[0020] Additionally, the outer shell is connected with the back support.
[0021] Furthermore, the openings in the outer shell are formed in locations that allow a user to grip the writing instrument without substantially touching the package.
[0022] In another aspect, both the first portion and the second portion of the mount are connected with the back support.
[0023] In another aspect, the back support and the outer shell are integrally formed as a single piece.
[0024] Finally, as can be appreciated by one skilled in the art, the present invention also comprises a method for forming the interactive package described herein.
BRIEF DESCRIPTION OF THE DRAWINGS
[0025] The objects, features and advantages of the present invention will be apparent from the following detailed descriptions of the various aspects of the invention in conjunction with reference to the following drawings, where:
[0026] FIG. 1 is a perspective-view illustration of an interactive package for a writing instrument according to the present invention, depicting a writing instrument disposed within the interactive package;
[0027] FIG. 2 is a left, side-view illustration of an interactive package for a writing instrument according to the present invention, with the writing instrument disposed therein;
[0028] FIG. 3 is a front-view illustration of an interactive package for a writing instrument according to the present invention, with the writing instrument disposed therein;
[0029] FIG. 4 is a back-view illustration of an interactive package for a writing instrument according to the present invention, with the writing instrument disposed therein; and
[0030] FIG. 5 is a top-view illustration of an interactive package for a writing instrument according to the present invention, with the writing instrument disposed therein.
DETAILED DESCRIPTION
[0031] The present invention relates to packaging for a writing instrument and, more particularly, to an interactive package for a writing instrument that allows a user to grasp the writing instrument without removing it from the packaging. The following description is presented to enable one of ordinary skill in the art to make and use the invention and to incorporate it in the context of particular applications. Various modifications, as well as a variety of uses in different applications will be readily apparent to those skilled in the art, and the general principles defined herein may be applied to a wide range of embodiments. Thus, the present invention is not intended to be limited to the embodiments presented, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
[0032] In the following detailed description, numerous specific details are set forth in order to provide a more thorough understanding of the present invention. However, it will be apparent to one skilled in the art that the present invention may be practiced without necessarily being limited to these specific details. In other instances, well-known structures and devices are shown in block diagram form, rather than in detail, in order to avoid obscuring the present invention.
[0033] The reader's attention is directed to all papers and documents which are filed concurrently with this specification and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference. All the features disclosed in this specification, (including any accompanying claims, abstract, and drawings) may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.
[0034] Furthermore, any element in a claim that does not explicitly state “means for” performing a specified function, or “step for” performing a specific function, is not to be interpreted as a “means” or “step” clause as specified in 35 U.S.C. Section 112, Paragraph 6. In particular, the use of “step of” or “act of” in the claims herein is not intended to invoke the provisions of 35 U.S.C. 112, Paragraph 6.
[0035] Before describing the invention in detail, an introduction is provided to give the reader a general understanding of the present invention. Next, a description of various aspects of the present invention is provided to give an understanding of the specific details.
[0036] (1) Introduction
[0037] The present invention relates to packaging for a writing instrument. Packaging of the prior art is typically a box-shaped container holding the writing instrument therein. Should a user (e.g., potential customer) decide to touch and/or feel the writing instrument in the prior art packaging, the user is required to remove the writing instrument from the packaging. For retailers, open packaging creates a problem as other potential customers may be dissuaded from purchasing a product with an opened package.
[0038] The present invention improves upon the prior art by allowing a user to touch and feel the writing instrument without removing it from the packaging. Through interactive packaging, a retailer can allow a potential customer to gain a better understanding of a product without destroying or damaging the packaging. Thus, the present invention is an interactive packaging with an opening configured therein. The opening is sized and shaped to permit a user's fingers to enter and grasp the writing instrument without otherwise touching the packaging.
[0039] (2) The Interactive Package
[0040] As shown in FIG. 1 , the present invention is an interactive package 100 for holding a writing instrument 102 therein. The interactive package 100 includes a back support 104 with a first end 106 and a second end 108 . The back support 104 is formed of any suitably durable material, non-limiting examples of which include plastic, paper, and cardboard. In some cases, it may be desirable to form the back support 104 of a clear plastic to allow viewing therethrough.
[0041] A mount 110 is included within the interactive package 100 for supporting the writing instrument 102 . The mount 110 is formed in any suitable manner to support the writing instrument 102 . As a non-limiting example, the mount 110 comprises a first portion 112 and a second portion 114 and the writing instrument 102 comprises a writing end 116 and a non-writing end 118 , with the mount 110 formed such that the first portion 112 mounts the non-writing end 118 and the second portion 114 mounts the writing end 116 . The mount 110 is formed of any suitably durable material, non-limiting examples of which include plastic, paper, and cardboard. For viewing purposes, it is desirable to form the mount 110 of a clear plastic.
[0042] An outer shell 120 is included to cover the mount 110 and a supported writing instrument 102 . The outer shell 120 defines a compartment 122 in combination with the back support 104 to securely protect the writing instrument 102 . The outer shell 120 and the back support 104 are formed in any suitable manner to define the compartment 122 therebetween. As non-limiting examples, both the outer shell 120 and the back support 104 are formed separately and thereafter attached with each other, and both the outer shell 120 and back support 104 are integrally formed together as a single piece to form the compartment 122 therein. The outer shell 120 is formed of any suitably durable material, non-limiting examples of which include plastic and paperboard. For viewing purposes, it is desirable that the outer shell 120 be formed of a clear plastic.
[0043] As can be appreciated by one skilled in the art, the mount 110 can be formed and attached with the interactive package 100 at any suitable location and in any suitable manner so long as the writing instrument 102 is supported by the mount 110 . As a non-limiting example, both the first portion 112 and the second portion 114 of the mount 110 are connected with the back support 104 . As another non-limiting example, the mount 110 is attached with the outer shell 120 . In another aspect, the mount 110 is positioned within the compartment 122 and held in place by the writing instrument 102 and the confines of the compartment 122 . In this aspect, the mount 110 is formed to frictionally fit between the back support 104 and the outer shell 120 .
[0044] As another example, the first portion 112 and second portion 114 of the mount 110 are formed separately from each other, with the first portion 112 being connected with the first end 106 of the back support 104 and the second portion 114 being connected with the second end 108 of the back support 104 .
[0045] In order to mount the writing instrument 102 , both the first portion 112 and the second portion 114 include a writing instrument holder 125 formed therein. The writing instrument holder 125 is any suitable configuration for holding the writing instrument 102 . As a non-limiting example, the writing instrument holder 125 is an indentation formed in the respective first 112 and second 114 portions. For example, the first portion 112 includes an indentation formed to frictionally fit the non-writing end 118 of the writing instrument 102 and the second portion 114 includes an indentation to frictionally fit the writing end 116 of the writing instrument 102 . In such an aspect, the writing instrument 102 is mounted between the two indentations such that it is held at both ends (i.e., writing end 116 and non-writing end 118 ).
[0046] Although the indentations may be formed at any suitable location within the mount 110 , it is desirable that the indentations are formed in the mount such that they are centered between the back support 104 and the outer shell 120 . By being centrally mounted, a mounted writing instrument 102 appears to float within the package 100 .
[0047] To enable a user to touch and feel an attached writing instrument 102 , the outer shell 120 includes an opening configuration 124 . The opening configuration 124 is sized and shaped to permit a user's fingers to enter and grasp the writing instrument 102 without otherwise substantially touching the outer shell 120 , mount 110 , or back support 104 . For example, the opening configuration 124 includes two openings, sized and shaped to permit a finger and a thumb of a user to enter and grasp the writing instrument 102 .
[0048] Furthermore, both the back support 104 and outer shell 120 can be formed in any suitable shape to contain a mount 110 therein and enable a user to grasp the writing instrument 102 through the opening configuration 124 . As non-limiting examples, the outer shell 120 and the back support 104 come together to form a compartment 122 having a cylindrical shape, a triangular shape, and a rectangular shape. As shown in FIG. 1 , the back support 104 is substantially planar with the outer shell 120 forming two outer portions of a triangular shaped compartment 122 . In this aspect, the mount 110 is formed in a triangular shape to fit within the compartment 122 .
[0049] To assist a user in displaying the interactive packaging 100 (and writing instrument therein), the back support 104 comprises a hanging mechanism 126 connected with the first end 106 for hanging the package 100 . The hanging mechanism 126 is any suitable mechanism to allow for hanging the package 100 , a non-limiting example of which includes a hanging tag.
[0050] For further illustration, FIGS. 2 through 5 show various view points of the interactive packaging 100 . FIG. 2 is a left, side-view illustration; FIG. 3 is a front-view illustration; FIG. 4 is a back-view illustration; and FIG. 5 is a top-view illustration. As seen in FIGS. 2 through 5 , the mount 110 includes an indentation-shaped writing instrument holder 125 for holding the writing instrument 102 in place.
[0051] As can be appreciated by one skilled in the art, the present invention also comprises a method for forming the interactive package described herein. The method comprises acts of forming a back support with a first end and a second end; connecting an outer shell with the back support to define a compartment in combination with the back support; and positioning a mount in the compartment for supporting a writing instrument. The method further comprises acts of forming each component of the interactive package such that it corresponds with the description of the interactive package described herein. | An interactive package for a writing instrument to allow a user to grip the writing instrument when the writing instrument is mounted in the package. The interactive package contains a back support connected with a mount, the mount having indentations to mount the writing instrument away from the back support so that the writing instrument appears to float inside the interactive package. An outer shell connects with the back support and surrounds the mount to create a compartment. Two openings in the outer shell allow a user to insert a finger and thumb through the respective openings to grip the writing instrument without touching any portion of the package. The user can then test the weight, look, and feel of the writing instrument while the writing instrument remains protected in the enclosure. | 1 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to an alkali- and heat-resistant inorganic fiber and, more particularly, to alkali- and heat-resistant inorganic fibers, in which the fiberizing temperature is approximately the same as those of customary rock fibers.
2. Description of the Prior Art
Heretofore, some of glass fibers have been known as alkali-resistant inorganic fibers. These glass fibers, however, show a high viscosity in the molten state such as, for example, 100 poises at 1,400° C. Owing to such high viscosity, one is unable to manufacture short fibers by a multirotor spinning process, which operates only under low melt viscosity conditions as in the case of rock fibers with a viscosity of several poises at 1,400° C. Moreover, there are other disadvantages for producing the alkali-resistant glass fibers. It is necessary to add zirconium oxide, which is expensive and, furthermore gives rise to an increased melting cost.
There has recently been disclosed alkali-resistant rock fibers which dispense with expensive zirconium oxide used in conventional alkali-resistant glass fibers U.S. Pat. No. 4,205,992, [Japanese Patent Application "Kokai" (Laid-open), No. 101,922/1979]. The disclosed fibers, however, have considerably high fiberizing temperature, comparing with those of customary rock fibers. This causes a remarkable increase in energy cost for manufacturing fibers of optimal diameter by means of a multirotor.
SUMMARY OF THE INVENTION
An object of this invention is to provide the alkali- and heat-resistant inorganic fiber manufactured by utilizing those natural rocks, slags and the like which are sufficiently available from the viewpoint of resources.
Another object of this invention is to provide the alkali- and heat-resistant inorganic fiber which can be manufactured economically by multirotor spinning process.
According to this invention, there is provided the alkali- and heat-resistant inorganic fibers comprising as major constituents
______________________________________ % by weight______________________________________SiO.sub.2 40-50CaO 0-10MgO 15-25Fe.sub.2 O.sub.3 + FeO 0-10Al.sub.2 O.sub.3 5-15MnO 2-15______________________________________ (provided that the total amount of CaO, Fe.sub.2 O.sub.3, FeO and MnO is limited within 20% by weight).
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 shows an electron microscopic photograph of the rock fiber specimen of Comparative Example 1 in Table 1, which has been subjected to the alkali resistance test.
FIG. 2 shows an electron microscopic photograph of the alkali- and heat-resistant rock fiber specimen of this invention (Example) in Table 1, which has been subjected to the alkali resistance test.
DETAILED DESCRIPTION OF THE INVENTION
When one intends to obtain simply good fibers from a batch material having comparatively low viscosity without paying attention to the alkali and heat-resistance, the SiO 2 content of the meltable material should be in the range of 35 to 50% by weight. If the SiO 2 content is below 35% by weight, it is difficult to obtain good short fibers of 2 to 10 μm in diameter, whereas if the SiO 2 content exceeds 50% by weight, the fiber formation by the multirotor spinning process becomes difficult owing to an increased melt viscosity. However, in view of the alkali and heat resistances intended in this invention, it is desirable to increase the SiO 2 content, and if the SiO 2 content is less than 40% by weight, it is difficult to obtain the fibers having satisfactory alkali and heat resistances, relating to the content of other alkaline oxides. After all, it is necessary that the SiO 2 content should be in the range of 40 to 50% by weight, most preferably 45 to 50% by weight.
For the purpose of improving the strength and heat resistance of fibers, the CaO content of the meltable material should be confined within 10% by weight. If the CaO content exceeds 10% by weight, the heat resistance, as well as physical properties of fibers, will be lowered. The most preferable CaO content is in the range of 0 to 6% by weight.
In the sense of replenishing the above defect of CaO and to adjust the viscosity of the meltable material to a value suitable for the multirotor spinning process, MgO should be present in an amount of 15 to 25% by weight. If the MgO content exceeds 25% by weight, not only the melt viscosity becomes too low to keep the optimal fiber formation, but also to secure the necessary amount of acidic oxides, resulting in lowering the alkali resistance of the fiber. On the other hand, if the MgO content is less than 15% by weight, the melt viscosity becomes too high to be suitable for the fiber formation. The most preferred MgO content should be in the range of 18 to 23% by weight.
Fe 2 O 3 and FeO are useful in improving the heat resistance and flexibility of the fiber of 2 to 10 μm in diameter. However, if their content exceeds 10% by weight, the alkali resistance of the fibers will be lowered. The most preferable content of Fe 2 O 3 plus FeO should be in the range of 0 to 8% by weight.
Alumina (Al 2 O 3 ) as well as silica (SiO 2 ) is effective in improving the fiber strength. However, with the increase in the Al 2 O 3 content, the melt viscosity becomes higher and the devitrefication temperature increases, resulting in an increase in melting energy cost. If the Al 2 O 3 content exceeds 15% by weight, the alkali resistance of the fibers will be lowered, whereas if it is below 5% by weight, good fibers may not be obtained. Therefore, the Al 2 O 3 content should be restricted to the range of 5 to 15% by weight; the most preferable content is in the range of 5 to 10% by weight.
Manganese oxide (MnO) has favorable effects of producing a uniform melt, and also of imparting the good alkali resistance to the fibers. In the case of the rock fibers, unlike the glass fibers, the addition of 2 to 15% by weight of MnO produces a sufficient decrease in melt viscosity and exhibits stabilizing and clarifying effects for the melt. For instance, the addition of 5% by weight of MnO will decrease the optimal fiber forming temperature by about 80° C. However, the addition of MnO over 15% by weight is not only unnecessary but also undesirable to secure the necessary amount of SiO 2 for the optimal fiber formation. If the MnO content is below 2% by weight, the function of the MnO as a flux is no longer exhibited. The most preferable MnO is in the range of 5 to 10% by weight.
Apart from the above-mentioned specification for each constituent, the total amount of MnO, CaO, Fe 2 O 3 and FeO should be within 20% by weight, because the total of 20% by weight makes the viscosity of the meltable material to the optimal level for the fiber formation by the multirotor spinning process. The superfluous addition of these constituents causes a negative factor for keeping the necessary amount of SiO 2 effective for the alkali resistance.
Titanium oxide (TiO 2 ) is contained in natural rocks or slags to be used for the meltable material as an impurity in the amount of about 2% by weight.
The major natural rock material to be used as raw material in producing the inorganic fibers of the composition as herein specified is found in olivine and metamorphous rocks thereof containing each 35% by weight or more of SiO 2 and MgO. Olivine has an advantage of being naturally occurred anywhere throughout Japan and available as raw material at low price.
A typical metamorphous rock of olivine is serpentine which can be used as a complete or partial substitute for olivine. However, as compared with olivine, generally the MgO content is smaller by about 5% and the Fe 2 O 3 content is larger by about 3%. It is, therefore, advantageous to use olivine from the economical and other viewpoints. In order to obtain the starting material of the composition as herein specified, one needs to adjust the composition of the above-noted major natural rock material by adding the calculated amounts of basalt, diabase, vermiculite, pyrophyllite, and iron ore slag for SiO 2 , CaO and Al 2 O 3 ; silica stone and silica brick for SiO 2 ; and manganese silicate ore, manganese carbonate ore, manganese oxide ore, and silicomanganese slag for MgO. The selection and combination of these natural ores or slags are not subject to any particular restriction, unless the final composition departs from that specified herein.
In manufacturing the alkali- and heat-resistant inorganic fibers of this invention by using the said natural rocks and slags, conventionally well-known equipments and methods can be applied. For instance, the compounded raw material is melted in a cupola by heating at 1410° to 1460° C., the resulting melt is allowed to flow downward onto the surface of spinning rotors to fiberize the molten material, and the fibers formed in this way is collected by means of an air stream blown-off around the spinning rotors.
EXAMPLE
The compounded raw material according to this invention, shown in the column of Example in Table 1, was melted in a conventional cupola by heating at 1,430° C. The resulting melt was allowed to flow downward onto the surface of spinning rotors to fiberize the molten material, and the fibers formed in this way were collected by means of an air stream blown-off around the spinning rotor.
In Comparative Examples 1 and 2, the compounded raw materials shown in Table 1 were also formed into fiber and collected in the same manner as described above, except that the raw materials were melted at 1,460° and 1,540° C., respectively, which were the optimal fiber forming temperatures as shown in Table 2.
TABLE 1______________________________________Comparative ComparativeExample 1 Example 2 Example______________________________________Slag 91% Basalt 55% Basalt 45%Silica Olivine 40 Olivine 40stone 9 Silica Silica stone 5 stone 10 Manganese oxide ore 5______________________________________
The composition and characteristics of the inorganic fibers obtained according to this invention were shown in Table 2, where are also shown the compositions and characteristics of other rock fibers not covered by the present invention (Comparative Examples 1 to 3).
TABLE 2__________________________________________________________________________ Comparative Comparative Comparative Example 1 Example 2 Example 3 Example__________________________________________________________________________SiO.sub.2 39.4% 45.0% 47.3% 45.8%CaO 37.4 16.0 5.4 5.6MgO 5.3 14.9 23.6 22.3Fe.sub.2 O.sub.3 + FeO 0.5 5.4 8.4 8.1Al.sub.2 O.sub.3 13.4 16.7 12.5 9.6MnO -- -- -- 4.1TiO.sub.2 1.7 0.5 1.1 1.5Others 2.3 1.5 2.6 3.0Melt viscosity1500° C. 4.8 poises 9.0 poises 5.3 poises 3.2 poises1450° C. 6.5 11.0 6.9 4.51400° C. 8.8 15.3 11.0 6.41350° C. 14.0 23.0 30.0 11.0Optimal fiber-forming tem- 1430- 1510- 1480- 1410-perature 1480° C. 1560° C. 1530° C. 1460° C.Average fiberdiameter 4.2μ 3.7μ 3.5μ 3.3μAlkali resis-tance (weightloss) 2.0% 1.8% 1.0% 1.0%Appearance of Discolored, Discolored; No change in No change infiber after brittle and disintegrated both appear- both appear-alkali resis- disintegrated upon touch ance and ance and shapetance test (see FIG. 1) with hand shape (see FIG. 2)Heat resis-tant tem- 700- 700- 840- 840-perature 720° C. 720° C. 860° C. 860° C.__________________________________________________________________________ Note:- (1) All percentages are by weight. (2) The Comparative Example 1 indicates the customary rock fibers. (3) The fibers of Comparative Example 2 are those of a composition not covered by the present invention. (4) The Comparative Example 3 correspond to the rock fibers disclosed in Japanese Patent Application "Kokai" (Laidopen) No. 101,922/1979. (5) Testing Method: (a) Alkali resistance: 500 cc of 1 N NaOH and about 10 g (weighed precisely) of the sample are placed together in a tightly stoppered 1lite polyethylene vessel and immersed in a hot water bath regulated at 80 ± 1° C. After 24 hours, the sample is washed with clean water, dried then measured the weight loss. (b) Heatresistant temperature: A disc having a diameter of 500 mm, a thickness of 50-80 mm and a specific gravity of 0.5 is placed under a loa of 10 g. The temperature of the disc is elevated at a rate of 10° C./minute until 500° C. and then at a rate of 5° C./minute. The temperature at which the sample has contracted in thickness by 10% is taken as the heatresistant temperature.
FIG. 1 is an electron scanning microscopic photograph (x 1,000) of the customary rock fibers after having been subjected to the alkali-resistance test described in the above procedure (a). The fibers were observed to be so deteriorated to show the roughness of the fiber surface and the occurrence of disintegrated fiber fragments.
FIG. 2 is an electron scanning microscopic photograph (x 1,000) of the inorganic fibers of this invention after having been subjected to the alkali resistance test described in the above procedure (a). It was observed that the fibers was kept their original shape, neither rough surface nor fiber fragments being detectable, indicating that the alkali resistance has been improved to a great extent.
As is apparent from Table 2, the fibers of this invention are superior in alkali resistance to those of the Comparative Examples 1 and 2. The fibers of the Comparative Example 3 show that alkali resistance is nearly equal to those of this invention. However, the example of this invention shows the lower optimal fiberizing temperature, which indicates the possibility of a remarkable saving in the melting energy. The heat-resistant temperature of the fibers of this invention is higher than that of the customary rock fibers by nearly 140° C.
The inorganic fibers of this invention having the good alkali and heat resistances, as described above, can be manufactured at low cost on commercial scale and used chiefly as a replacement of asbestos in asbestos-cement boards. | The inorganic fiber of this invention comprising as major constituents
______________________________________
% by weight______________________________________SiO 2 40-50CaO 0-10MgO 15-25Fe 2 O 3 + FeO 0-10Al 2 O 3 5-15MnO 2-15______________________________________
(provided that the total amount of CaO, Fe 2 O 3 , FeO and MnO is about 20% by weight) is excellent in alkali- and heat-resistances and is useful as a replacement of asbestos in asbestos-cement boards. Titanium oxide (TiO 2 ) is contained in natural rocks or slags to be used for the meltable material as an impurity in the amount of about 2% by weight. | 2 |
[0001] CROSS-REFERENCED APPLICATION
[0002] This application is a continuation application of U.S. patent application Ser. No. 12/009,221, filed on Jan. 17, 2008, which is incorporated herein by reference in its entirety.
BACKGROUND OF THE DISCLOSURE
[0003] 1. Field of the Disclosure
[0004] A method of preparing a frozen beverage by blending a slug or nugget of ice particles and a flavor ingredient in a disposable vessel.
[0005] 2. Description of the Prior Art
[0006] In recent years, the popularity of “frozen drinks” has been increasing dramatically. These drinks typically consist of a mixture of flavorings, fruit puree, coffee, liquor, dairy products and/or other ingredients and a finely-divided ice/water mixture that has the consistency of a thin paste. This type of drink is often called a Smoothie at branded Jamba Juice or a “slush” drink at branded 7/11 or a blended coffee like branded Starbuck's Frapachino.
[0007] Historically, from the 1940's a frozen drink was made by placing the ingredients of the drink, including ice in the form of cubes or crushed ice, in a blender pitcher like the branded Waring blender. The blender is then operated for the considerable amount of time required to reduce the ice to a finely-divided state. The mixture is then transferred to a drinking glass or disposable cup for consumption. Then in 1986 John Herbert, U.S. Pat. No. 4,681,030, invented a better way of doing this by first shaving ice into a blender and then blending the ingredients. This increased the speed and consistency of the final ice slurry because the shaved ice is made by pressing ice against a rotating blade, which was far more efficient than having ice cubes bouncing around in a blender and only making contact with blender blade after the ice cubes fall through the solution only to bounced back up again after hitting the blade. In particular, U.S. Pat. No. 4,681,030 shows an apparatus for preparing frozen drinks, in which an ice-shaving machine is combined with a blender in a single unit, the output of the ice-shaving machine being discharged directly into the blender cup. The ice-shaver and the blender are electrically wired together, and programmable timing means are provided to permit selective control of the periods of time over which the ice-shaver and blender operate, so that, by the momentary activation of a single switch button, the apparatus may be activated and will automatically deliver the appropriate amount of ice to the blender cup and will turn on the blender at the appropriate time and for the appropriate amount of time.
[0008] In 1994 various inventors, such as Reese and Hanson, U.S. Pat. No. 5,619,901, added automatic dispensers of flavorings “to provide, in a beverage dispensing machine having a blender, a portion control means to dispense a precise predetermined amount of the drink mix and shaved ice, respectively, thereby avoiding waste and inconsistent flavors. Specifically, U.S. Pat. No. 5,619,901 relates to a beverage dispensing machine assuring precise portion control of the respective drink mixes being dispensed, and the precise amount is adjustable within certain limits. The drink mixes are in respective beverage receptacles (or drink tubes) arranged in a side-by-side relationship with respect to each other, and a plurality of selection buttons are disposed directly below the receptacles in substantial vertical alignment therewith. A counter and a interrupt button, respectively, are also provided on the control panel. The level of the drink mixes as well as the ice in the reservoir, are readily visible at all times. Upon initiation of the blending cycle, the blender motor is started, and after a first time delay, the drink mix is discharged into the blender for a first time period. Upon a second time delay following initiation of the discharge of the mix, the ice shaver motor continues for a second time period; and the blender motor continues after discharge of the mix and delivery of the shaved ice.
[0009] U.S. Pat. No. 3,505,075 discloses a method and apparatus for preparing a frozen slush beverage where ice in chunk form is mixed with flavoring agent under conditions causing carbon dioxide part of the gas to be absorbed by the mixture producing the frozen beverage.
[0010] U.S. Pat. No. 3,615,673 describes a disposable cup containing beverage ingredients including ice placed within a rigid receptacle. A closure is moved into the open top of the cup sealing its interior from the ambient atmosphere. A cutter carried by the closure is rotated within the cup to agitate the ingredients while carbon dioxide is forced into the cup through the closure at a pressure which would normally deform the cup walls. Following the agitation, the closure lifts the cup under the influence of the pressurized carbon dioxide.
[0011] U.S. Pat. No. 4,932,223 shows an auger-type ice-making apparatus includes a new and improved auger or auger assembly having one or more generally spiral flight portions with one or more grooves formed transversely across the outer edges of the flight portions. The grooves interrupt the generally spirally-extending contact between the outer auger edges and the inner surface of an evaporator housing, thus reducing the area of contact therebetween and, as a result, reducing the load on the auger bearings. The grooves also provide a stress-relieved area on the flight portion during scraping of ice particles from the inner surface of the evaporator and tend to balance the forces on the auger bearings.
[0012] U.S. Pat. No. 4,745,773 relates to an apparatus for making a soft ice-drink comprising an ice mechanism including a shaver casing having a slit to which a shaving blade is exposed and a shaved ice discharge chute, rotatable blades, provided within the shaver casing, for cooperating with the shaving blade to shave ice blocks charged into the shaver casing, and a mixing mechanism under the ice shaving mechanism, including rotary blades, rotatably supported within a container disposed beneath the shaved ice discharge chute, for mixing together a liquid material such as a syrup present within the container and shaved ice pieces discharged into the container and smashing the shaved ice pieces into granules of ice.
[0013] U.S. Pat. No. 5,803,377 teaches a frozen drink machine and a method for making frozen drinks from a frozen substance which has been frozen into a cup. The cup contains a frozen substance positioned in a cup support located in the frozen drink machine. A rotatable blade having features for grinding the frozen substance and for aerating the ground frozen substance is lowered into the cup, grinding the frozen substance while a liquid is simultaneously introduced into the cup. In an alternative embodiment, a second blade is provided which incorporates air into the liquid before the liquid is introduced into the cup.
[0014] U.S. Pat. No. 5,911,749 relates to an auger-type ice maker comprising partitions projectingly provided on the outer periphery of a pressing head which has been inserted and fixed to the upper portion of an ice-making cylinder 1 , wherein fixed blades are formed at the lower portion of the partitions so as to be offset in the radial direction, and wherein the tip of the inner circumference side portion thereof is situated above the greater diameter portion of the auger provided with a spiral blade. In the above construction, the offset corner portion is provided with a curvature. Accordingly, ice can be prevented from being compressed to and adhering to the corner portion. Thus, the transporting resistance of ice at the lower portion of the partitions projectingly provided to the outer periphery of the pressing head can be reduced, thereby preventing decreasing in ice-making capabilities and abnormal sounds or vibrations being emitted owing to ice jamming occurring.
[0015] U.S. Pat. No. 6,730,348 shows a method for preparing a flavored confection using a disposable container of a neutral-flavored mix, transferred from a storage freezer to a tempering freezer. The container is removed from the tempering freezer, and a selected syrup is pumped from a carton into the disposable container for blending while the mix remains chilled.
[0016] U.S. Pat. No. 6,772,675 discloses a frozen beverage mixing unit has a hollow housing with an open bottom and a shaving disc with a cutting knife is rotationally mounted inside the housing. A piston moves above the shaving disc pushing a frozen product into a contact with the cutting blades of the shaving disc. A plurality of pumps deliver a pre-determined amount of a selected additive, such as alcohol, syrup, carbonated water or water, on top of the shaving disc to mix with the ice crystals created by the shaved frozen product. The additive is mixed with the shaved frozen product in a mixing container placed below the shaving disc.
[0017] U.S. Pat. No. 6,068,875 relates to a method for preparing a flavored slurried confection includes the use of a disposable serving container holding an individual serving of a neutral flavored mix which has a freezing point temperature lower than normally found for that of water. A large supply of the mix filled containers is stored in a storage freezer for maintaining the neutral flavored mix at a storage temperature, such as is typical of a food storage freezer for a restaurant. A desired quantity of the mix filled containers is then transferred from the storage freezer to a tempering freezer, generally close to a preparation and serving area, for maintaining the neutral flavored mix at a desirable blending temperature. The mix filled container is then removed from the tempering freezer for preparation of a flavored confection, such as a flavored shake. In preparing the flavored confection, a small quantity of a selected syrup is pumped from a selected bag-in-the-box styled carton into the mix filled container for blending the selected syrup with the neutral flavored mix while the mix remains chilled at the blending temperature. The small quantity of syrup adds provide the selected flavor to the neutral flavored mix for forming the flavored slurried confection which is then served within the disposable serving container.
[0018] U.S. Pat. No. 7,278,275 teaches a mechanism for dispensing ice in each of three selected forms, namely, cubed, crushed and shaved. This mechanism includes a reservoir arranged to hold a supply of ice cubes, a dispensing zone, a delivery mechanism arranged for dispensing ice cubes from said reservoir to said dispensing zone, an ice crushing mechanism located in said dispensing zone arranged to selectively crush ice, an ice shaving mechanism located in said dispensing zone arranged to selectively shave ice, and a control mechanism arranged to selectively activate said ice crushing mechanism and said ice shaving mechanism upon receipt of an appropriate input from a user.
[0019] Additional examples of the prior art are found in U.S. Pat. No. 2,855,007; U.S. Pat. No. 5,192,131; U.S. Pat. No. 5,619,901; U.S. Pat. No. 5,833,362; U.S. Pat. No. 5,863,118; U.S. Pat. No. 6,196,712; U.S. Pat. No. 6,283,627; U.S. Pat. No. 6,293,691; U.S. Pat. No. 6,338,569; U.S. Pat. No. 6,616,323: U.S. Pat. No. 6,945,157 and U.S. 2002/0194999.
[0020] Many of these devices automatically delivered the ingredients. However, one of the principal problems with such method of making frozen drinks is the time and effort it takes to pour the drink out of the blender and into a serving glass or disposable cup and then having to thoroughly wash the blender. Also, if the blender is not washed properly because they are quickly trying to serve another customer who is waiting for a strawberry drink, but just after a chocolate drink is made, then it is easy to get cross contamination where there is chocolate inside the strawberry drink. The problem of washing a blender picture is greater than most vessels because there is a lot of surface area in the picture when compared to the size of the drink being served and also, because there is a blade inside the picture, there are many nooks and crannies that can “hold onto” the food.
[0021] A further problem associated with the conventional method arises from the amount of time consumed delivering drinks in serial fashion. If there is only 1 blender and 10 drinks are ordered, then they have to be made one after the other and little simultaneous actions can take place. So if it takes 1 minute to make a drink, it will take 10 minutes to make 10 drinks.
[0022] A further problem associated with the conventional method arises from the fact the staff must only do one thing when they make the drink, which is make the drink.
[0023] They cannot “multi-task” and help another customers while they are making the drinks because they have to “tend” the machine by emptying and washing blenders, pouring drinks, etc. in other words, if they stop tending the machine, then the drink making process will stop.
[0024] It is therefore an object of the present disclosure to provide apparatus which can make frozen drinks quickly and efficiently and to do so in an automatic fashion directly in the serving cup without the use of a blender.
[0025] Various attempts have been made to blend inside a disposable cup, but the problem has been that the cup is too big, so the customer feels he has been cheated with a ⅔ cup of drink. The solution to this was to put a steel ring around the top of the cup to temporarily extend the height of the cup. The problem with this is that the metal ring needs to be washed or it will cause cross contamination and so on.
[0026] In addition, attempts have been made to blend inside a disposable cup such as Miller, U.S. Pat. No. 6,068,875 where he blends a drink that already has a neutral base material inside the cup and his machine is used to add syrups and flavorings to the disposable cup. However, this requires that a large storage of pre-filled cups be kept in a frozen state at the point of delivery. This can cause an inventory problem in the stores. Generally there is limited space in the retail area, therefore, only a few cups can be held in this area without consuming too much space. In addition, the refrigerated walk-in freezers are usually crowded with other products. Although there are many machines that use a pre-filled cup from a factory and the blending machine is used to finish-off the drink with the addition of either syrup, water or heat, they all have the problem of taking up refrigerated inventory space in a retail store.
SUMMARY
[0027] The present disclosure relates to a method and apparatus for preparing a single serving of a frozen slurry beverage in a disposable drink container or cup.
[0028] The apparatus for preparing a single serving of a flavored frozen slurry beverage comprises an ice making device including an ice dispensing station and ice dispensing nozzle to supply fine frozen particles of water in the form of ice flakes and/or ice nuggets of compressed ice flakes, a liquid beverage mix dispensing nozzle to supply a flavored liquid beverage mix and a beverage blending device including a beverage blending station and blender to blend the fine frozen particles of water and the flavored liquid beverage mix into a substantially uniform frozen slurry beverage of a predetermined consistency.
[0029] When in the form of ice flakes, the fine frozen particles of water of the present disclosure comprises from about 81 percent or frozen water to about 89 percent ice or frozen water by weight with the remainder unfrozen water. When in the form of compressed ice flakes or ice nuggets, the fine frozen particles of water comprises from about 89 percent ice or frozen water to about 97 percent ice or frozen water by weight with the remaining unfrozen water.
[0030] The method of the present disclosure comprises the steps of creating fine frozen particles of water; placing a disposable drink container or cup on the ice dispensing station beneath the ice dispenser nozzle; dispensing a predetermined quantity or amount of fine frozen particles of water from the ice dispensing nozzle into the disposable drink container or cup; removing the disposable drinking container or cup containing the predetermined quantity or amount of fine frozen particles of water from the ice dispensing station; placing the disposable drink container or cup containing the predetermined quantity or amount of fine frozen particles of water on the liquid beverage mix station beneath the liquid beverage mix dispensing nozzle; dispensing a predetermined quantity or amount of flavored liquid beverage mix from the liquid beverage mix dispensing nozzle into the disposable drink container or cup containing the predetermined quantity or amount of fine frozen particles of water; removing the disposable drink container or cup containing the unmixed predetermined quantities or amounts of fine frozen particles of water and flavored liquid beverage mix from the liquid beverage mix station; placing the disposable drink container or cup containing the unmixed predetermined quantities or amounts of fine frozen particles of water and flavored liquid beverage mix on the beverage blending station of the beverage blending device; lowering the rotating blender blade of the beverage blending device into the interior of the disposable drink container or cup and into the unmixed predetermined quantities or amounts of fine frozen particles of water and flavored liquid beverage mix; raising the rotating blender blade of the beverage blending device above the disposable drink container or cup containing the substantially uniform frozen slurry beverage of a predetermined consistency; and removing the disposable drink container or cup with the substantially uniform frozen slurry beverage from the beverage blending station of the beverage blending device.
[0031] The disclosure accordingly comprises the features of construction, combination of elements, and arrangement of parts which will be exemplified in the construction hereinafter set forth, and the scope of the disclosure will be indicated in the claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0032] For a fuller understanding of the nature and object of the disclosure, reference should be had to the following detailed description taken in connection with the accompanying drawings in which:
[0033] FIG. 1 is a schematic of the steps of the method of the present disclosure.
[0034] FIG. 2 is a perspective view of a ice making device for use with the present disclosure.
[0035] FIG. 3 is a perspective view of a beverage blending device for use with the present disclosure.
[0036] Similar reference characters refer to similar parts throughout the several views of the drawings.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0037] The present disclosure relates to a method and apparatus for preparing a single serving of a frozen slurry beverage in a disposable drink container or cup. The figures and descriptions depict and describe an exemplary preferred embodiment of the present disclosure for purposes of illustration. One skilled in the art will readily recognize that the principles of the instant disclosure are equally applicable to other methods and types of apparatuses.
[0038] FIG. 1 is a schematic of the apparatus for preparing a single serving of a flavored frozen slurry beverage 10 in a disposable drink container or cup 12 comprising an ice making device generally indicated as 14 including an ice dispensing station and ice dispensing nozzle indicated as 16 and 18 respectively to supply fine frozen particles of water 20 in the form of ice flakes and/or ice nuggets of compressed ice flakes, a liquid beverage mix device 22 including a liquid beverage mix station and liquid beverage mix dispensing nozzle indicated as 24 and 26 respectively to supply a flavored liquid beverage mix 28 and a beverage blending device generally indicated as 30 including a beverage blending station and blender indicated as 32 and 34 to blend the fine frozen particles of water 20 and the flavored liquid beverage mix 28 into a substantially uniform frozen slurry beverage 10 of a predetermined consistency.
[0039] When in the form of ice flakes, the fine frozen particles of water of the present disclosure comprises from about 81 percent ice or frozen water to about 89 percent ice or frozen water by weight with the remainder unfrozen water. Preferably, the ice flakes comprise about 85 percent ice or frozen water by weight with the remainder unfrozen water. When in the form of compressed ice flakes or ice nuggets, the fine frozen particles of water comprises from about 89 percent ice or frozen water to about 97 percent ice or frozen water by weight with the remaining unfrozen water. Preferably, the compressed ice flakes comprise about 93 percent ice or frozen water by weight with the remainder unfrozen water.
[0040] The ice making device 14 may comprise an ice making machine as disclosed in U.S. Pat. No. 4,932,223 or U.S. Pat. No. 5,911,749. Each such apparatus is capable of producing ice flakes and compressing ice flakes into ice nuggets. FIG. 2 shows a commercial version of the Scotsman ice maker disclosed in the '223 patent. The ice making device 14 comprises an enclosure or housing 36 to house an ice auger 38 within the upper portion thereof and an ice compressor 40 disposed to receive ice flakes from the ice auger 38 to form ice nuggets from the ice flakes. The ice dispensing nozzle 18 is attached to the front of the enclosure or housing 36 to receive either ice flakes or ice nuggets produced by the ice making device 14 and to dispense the ice flakes or ice nuggets into a disposable drink container or cup 12 placed on the ice dispensing station 16 . An actuator or switch 42 is mounted to the front of the enclosure or housing 36 to selectively dispense the fine frozen particles of water from the ice dispensing nozzle 18 when actuated or pressed. Water is supplied to the ice making device 14 from a water source (not shown) to the ice forming assembly (not shown) of the ice making device 14 through a water supply conduit 44 .
[0041] The liquid beverage mix device 22 including the liquid beverage mix station 24 and liquid beverage mix dispenser nozzle 26 may comprise a liquid beverage mix dispensing apparatus capable of dispensing a single flavor liquid beverage mix or multiple flavor liquid beverage mixes similar to the machine shown in U.S. Pat. No. 5,619,901 to supply the flavored liquid beverage mix 28 from the liquid beverage mix dispensing nozzle 26 to the disposable drink container or cup 12 container with the fine particles of frozen water 20 therein placed on the liquid beverage mix station 24 .
[0042] The beverage blending device 30 to blend the fine frozen particles of water 20 and the flavored liquid beverage mix 28 into the substantially uniform frozen slurry beverage 10 to a predetermined consistency includes the beverage blending station 32 and blending implement 34 and a blender positioning mechanism generally indicated as 45 to selectively position the blending implement 34 as shown in FIG. 3 .
[0043] The beverage blending device 30 comprises a cabinet including a frame or housing including a base 46 and top or cover 48 disposed in spaced relationship relative to each other by at least one substantially vertical wall or frame support 50 .
[0044] The blending implement 34 comprises a lower blender blade 52 and an intermediate substantially vertical coupler member or blender shaft 54 attached to a blender motor 56 coupled to a power source (not shown) to selectively rotate the blender blade 52 and intermediate substantially vertical coupler member or blender shaft 54 during the blending process. The blender motor 56 is affixed to the blender positioning mechanism 45 as described more fully hereinafter to selectively move the blender motor 56 and blending implement 34 vertically relative to the disposable drink container or cup 12 containing the fine frozen particles of water 20 and the flavored liquid beverage mix 28 when placed on the blending beverage station 32 . Specifically, the blender positioner mechanism 45 moves the blender blade 52 vertically into the disposable drink cup or container 12 and oscillates vertically up and down within the fine frozen particles of water 20 and the flavored liquid beverage mix 28 to mix and blend the beverage components into the substantially uniform frozen slurry beverage 10 to a smooth predetermined consistency.
[0045] The blender positioner mechanism 45 comprises a positioner motor 58 attached to the top or cover 48 of the cabinet coupled to a power source (not shown) to selectively rotate a substantially vertical externally threaded screw member or shaft positioner 60 and a positioning member 62 including an internally threaded aperture 64 to selectively move the positioning member 62 , blender motor 56 and blender implement 34 vertically relative to the blending beverage station 32 . The blender motor 56 is attached to the positioning member 62 .
[0046] The blender positioner mechanism 45 further includes a positioner guide to guide the vertical movement of the positioner member 62 , blender motor 56 and blending implement 34 . In particular, the positioner guide comprises an upper and lower substantially parallel substantially horizontal guide member indicated as 66 and 68 respectively each including a centrally disposed aperture 70 to operatively receive the substantially vertical externally threaded screw member or positioner shaft 60 therethrough and a pair of substantially parallel, substantially vertical cylindrical guide members each indicated as 72 attached to corresponding end portions of the upper and lower substantially parallel substantially horizontal guide members 66 and 68 . The positioner member 62 includes a circular guide aperture 74 formed through each end portion thereof to slideably receive a corresponding substantially parallel, substantially vertical cylindrical guide member 76 therethrough to guide the vertical movement of the blender implement 34 and blender motor 56 attached to the positioner member 62 . Of course, the substantially parallel, substantially vertical guide member 72 and guide apertures 74 may have corresponding rectilinear or other corresponding shapes.
[0047] The blending station 32 comprises a support surface 78 and a retainer recess 80 to receive and support the lower portion of a disposable drink container or cup 12 containing the fine frozen particles of water 20 and the flavored liquid beverage mix 28 to be mixed or blended into the substantially uniform frozen slurry beverage 10 of a predetermined consistency or viscosity. In addition, at least one flexible retainer element or arm 82 may be attached to a partial wall 84 to grip or hold the side of the disposable drink container or cup 12 when supported on the support surface 78 .
[0048] The cabinet may comprise an enclosure having an automated wash device 86 disposed therein to periodically wash the interior thereof automatically.
[0049] The method of the present disclosure comprises the steps of:
supplying water to the ice making device 14 through the water supply conduit 44 , creating fine frozen particles of water of ice flakes 20 within the ice making device 14 , compressing the ice flakes 20 into ice nuggets within the ice making device 14 , placing a disposable drink container or cup 12 on the ice dispensing station 16 of the ice maker device 14 beneath the ice dispenser, nozzle 18 , dispensing a predetermined quantity or amount of fine frozen particles of water 20 from the ice dispensing nozzle 18 into the disposable drink container or cup 12 , removing the disposable drink container or cup 12 containing the predetermined quantity or amount of fine frozen particles of water 20 from the ice dispensing station 16 , placing the disposable drink container or cup 12 containing the predetermined quantity or amount of fine frozen particles of water 20 on the liquid beverage mix station 24 of the liquid beverage mix device 22 beneath the liquid beverage mix dispensing nozzle 26 , dispensing a predetermined quantity or amount of flavored liquid beverage mix 28 from the liquid beverage mix dispensing nozzle 26 into the disposable drink container or cup 12 containing the predetermined quantity or amount of fine frozen particles of water 20 , removing the disposable drink container or cup 12 containing the unmixed predetermined quantities or amounts of fine frozen particles of water 20 and flavored liquid beverage mix 28 from the liquid beverage mix station 24 of the liquid beverage mix device 22 , placing the disposable drink container or cup 12 containing the unmixed predetermined quantities or amounts of fine frozen particles of water 20 and flavored liquid beverage mix 28 on the beverage blending station 32 of the beverage blending device 30 , securing the disposable drink container or cup 12 containing the unmixed predetermined quantities or amounts of fine frozen particles of water 20 and flavored liquid beverage mix 28 on the beverage blending station 32 of the beverage blending device 30 , rotating the blender blade 52 of the beverage blending device 30 , lowering the rotating blender blade 52 of the beverage blending device 30 into the interior of the disposable drink container or cup 12 and into the unmixed predetermined quantities or amounts of fine frozen particles of water 20 and flavored liquid beverage mix 28 , oscillating the rotating blender blade 52 of the beverage blending device 30 vertically within the disposable drink container or cup 12 containing the unmixed predetermined quantities or amounts of fine frozen particles of water 20 and flavored liquid beverage mix 28 through the interface therebetween to thoroughly mix the unmixed predetermined quantities or amounts of fine frozen particles of water 20 and flavored liquid beverage mix 28 together into a substantially uniform frozen slurry beverage of a predetermined consistency, raising the rotating blender blade 52 of the beverage blending device 30 above the disposable drink container or cup 12 containing the substantially uniform frozen slurry beverage of a predetermined consistency and, removing the disposable drink container or cup 12 with the substantially uniform frozen slurry beverage 10 from the beverage blending station 32 of the beverage blending device 30 .
[0066] As previously described, the fine frozen particles of water of the present disclosure preferably comprises ice flakes of about 85 percent ice or frozen water by weight with the remainder unfrozen water or ice nuggets of about 93 percent ice or frozen water by weight with the remainder unfrozen water.
[0067] It will thus be seen that the objects set forth above, among those made apparent from the preceding description are efficiently attained and since certain changes may be made in the above construction without departing from the scope of the disclosure, it is intended that all matter contained in the above description or shown in the accompanying drawing shall be interpreted as illustrative and not in a limiting sense.
[0068] It is also to be understood that the following claims are intended to cover all of the generic and specific features of the disclosure herein described, and all statements of the scope of the disclosure which, as a matter of language, might be said to fall therebetween. | A method for preparing a single serving frozen beverage in a single serving disposable drink container, the method comprising: dispensing a predetermined quantity of ice into the single serving disposable drink container, dispensing a predetermined quantity of flavorings into the single serving disposable drink container, blending the ice and the flavorings by a blender in the single serving disposable drink container, and securing the single serving disposable drink container during the blending step, the single serving disposable drink container being received by a retainer recess, the retainer recess receiving and supporting only a lower portion of the single serving disposable drink container. | 0 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a vaginal stimulator and a device for the treatment of female urinary incontinence by the way of electrical stimulation applied to the pelvic floor musculature and surrounding structures.
2. Description of the Prior Art
Female urinary incontinence is a condition with severe economic and psychosocial impact. There are several types of urinary incontinence but all are characterized by an inability to restrain urinary voiding. The three most frequent types of urinary incontinence are the stress incontinence, characterized by the involuntary loss of urine from the urethra during physical exertion, the urge incontinence or involuntary loss of urine associated with an abrupt and strong desire to void, and the mixed urinary incontinence which results from both urge incontinence and stress incontinence.
Various methods have been propesed for improving the strength and tone of the pelvic floor muscle group. In 1948, Arnold Kegel described pelvic floor exercises as a treatment option in stress incontinence and invented a set of exercises to strengthen and support the pelvic floor. The purpose of the Kegel exercises is to increase volume and to develop stronger reflex contractions following quick rise in intra-abdominal pressure. Many women find these Kegel exercises difficult and uncomfortable to perform and the major obstacle to success with Kegel exercises is the tendency among women to give up or forget how to correctly do the exercises.
Electrical stimulation of the pelvic floor is an effective therapy both for stress incontinence and urge incontinence. Electrical stimulation of the pelvic floor automates Kegel exercises through the use of direct electrical stimulation of the vagina and bladder muscle. Electrical stimulation of the pelvic floor to treat stress incontinence and urge incontinence was first studied in the early 1960's and clinical studies from the 70's through 90's have reaffirmed its effectiveness.
With the first electrical stimulation methods used to treat female urinary incontinence, women had to go in a medical setting to undergo electrical stimulation session of their pelvic floor muscle. Later electrical stimulators for home treatment appeared. These devices are usually in two parts: an inside vagina part which is a vaginal plug with electrodes intended to be in contact with the vagina wall and an outside vagina part which can be the pulse generator and a power supply or a power supply only if the pulse generator is inside the vaginal plug. Such devices are not convenient because of the cable(s) between the inside vagina part and the outside vagina part. Moreover, hygiene problems are encountered when the vaginal plug has not been completely cleaned before its insertion in the vagina.
Other devices are used with a special condom which must be disposed of and changed after each use.
Said devices of the prior art are not well accepted by the women because they are exacting and difficult to use. With some devices the insertion and the extraction of the plug are not easy, the presence of cables and/or cumbersome equipment is not comfortable, the plugs are difficult to clean, the user must have batteries in advance, and in the case of devices used with condoms the user must have condoms in advance. There is then a need for a pelvic floor muscle electrical stimulation device effective, convenient to use and easy to insert, extract and clean.
SUMMARY OF THE INVENTION
The present invention is directed to a vaginal stimulator with a body adapted to be inserted in women's vagina to electrically stimulate the pelvic floor musculature and surrounding structures, comprising a battery as power supply, means for applying preprogrammed instructions concerning the current frequency adapted to the type of incontinence to be treated and the treatment duration.
Advantageously, said means for applying preprogrammed instructions comprise a microcontroller to select the pulse frequency and the working time given by an outer electronic control system. In a preferred embodiment of the invention, said electronic control system is located in a case comprising a housing for said stimulator, when not in use.
Preferably, said vaginal stimulator body comprises on its surface, at least two sets of conductors, a first set being used as electrodes to transmit electrical pulses to the pelvic floor musculature, and a second set, which, jointly with the first one, is able to transmit the instructions of the operator to the vaginal stimulator microcontroller.
Said vaginal stimulator is advantageously watertight.
It is convenient that an eyelet be provided at one end of the vaginal stimulator body, with a guide to thread a string into the eyelet.
The invention is also directed to a device for the treatment of female urinary incontinence by electrical stimulation applied to the pelvic floor musculature and surrounding structures, comprising a vaginal stimulator as above defined and a carrying and control case, without cable linking one to the other.
In a preferred embodiment, the carrying and control case comprises a housing for said vaginal stimulator, a transformer with charge circuitry to charge the vaginal stimulator battery, an electronic control system to transmit the instructions given by the operator.
Said housing is advantageously provided with metal contacts arranged to be in contact with the conductors of the vaginal stimulator when put into the housing.
It further comprises a wedge adapted to go into the vaginal stimulator eyelet and intended to secure the position of the vaginal stimulator in the housing so that the conductors of the vaginal stimulator be always in contact with the corresponding metal contacts of the housing.
The above instructions are given by the operator to the vaginal stimulator microcontroller through control knobs.
The programmable vaginal stimulator of the present invention is very convenient and easy to use. Between each use the rechargeable battery of the vaginal stimulator is recharging when the vaginal stimulator is in its housing and the cover of the carrying and control case is closed. Before each use the user has only to select the type of incontinence and program the use time. Usually, this programming is done once and for all before the first use. After having thread a piece of string through the eyelet of the vaginal stimulator with the help of the guide string, the user can lubricate the vaginal stimulator to make easier its insertion in the vagina. Then the vaginal stimulator is inserted into the vagina like a tampon, just so it disappears into the vaginal opening. When the use time is passed, the device user takes out the vaginal stimulator from the vagina, cuts the string, throws it away, cleans the vaginal stimulator with mild soap or alcohol, or other disinfectants, wipes it, places it back in its resting nest and closes the cover of the carrying and control case. The battery will recharge automatically.
BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 is a view of the vaginal stimulator according to the invention.
FIG. 2 is an exploded view of the inside of the vaginal stimulator.
FIG. 3 is a view from the inside of a carrying and control case, intended for containing a vaginal stimulator.
FIG. 4A is a block diagram illustrating the inside stimulator electronic circuit, and
FIG. 4B is a block diagram illustrating the inside carrying and control case electronic control system.
DETAILED DESCRIPTION
FIG. 1 illustrates a vaginal stimulator according to the invention. Said vaginal stimulator ( 1 . 1 ) is composed of a cylinder-shaped, polymer material body with two rounded ends. Such a stimulator may, for example, have the following dimensions: length 8 centimeters, diameter 2.5 centimeters.
The vaginal stimulator ( 1 . 1 ), which comprises a division floor ( 2 . 4 ), includes the following elements:
1. Three conductors ( 1 . 2 ), ( 1 . 3 ), ( 1 . 4 ) which are included in the exterior polymer material body surface. Two of the three conductors are used as electrode +( 1 . 2 ) and electrode−( 1 . 3 ) to carry the electric pulses coming from an inside vaginal stimulator microcontroller (FIG. 2 : ( 2 . 2 )) to the vaginal musculature when the vagina stimulator is operating. Two of the three conductors ( 1 . 2 ), ( 1 . 4 ) are used to charge the inside vaginal stimulator rechargeable battery (FIG. 2 : ( 2 . 1 )) and said three conductors ( 1 . 2 ), ( 1 . 3 ), ( 1 . 4 ) are used to transmit instructions to the inside vaginal stimulator microcontroller (FIG. 2 : ( 2 . 2 )) when the device user is programming the vaginal stimulator.
2. An eyelet ( 1 . 5 ) for string connection. An about 20 centimeters bit of string is threaded through the vaginal stimulator eyelet ( 1 . 5 ) and the two ends of the string are knotted before the use of the vaginal stimulator. This bit of string enables an, easier extraction of the vaginal stimulator at the end of the use time.
3. A string guide ( 1 . 6 ) to easier thread the string in the vaginal stimulator eyelet ( 1 . 5 ).
4. A rechargeable battery ( 2 . 1 ) which is the power supply of the vaginal stimulator ( 1 . 1 ). This rechargeable battery is charged through two conductors ( 1 . 2 ), ( 1 . 4 ) of the vaginal stimulator ( 1 . 1 ) and two corresponding metal contacts of an outside device, advantageously of a carrying and control case adapted for housing the vaginal stimulator.
5. A microcontroller ( 2 . 2 ) with microprocessor, random access memory and input output system, to generate the electric pulses necessary to make working the vaginal stimulator ( 1 . 1 ) and execute the different orders given by the operator.
6. An inside round seal ( 2 . 3 ) which permits to make the vaginal stimulator watertight and easy to clean with mild soap, alcohol or other disinfectants.
The block diagram of the inside stimulator electronic circuit is given on FIG. 4 A. As above-mentioned, the microcontroller ( 2 . 2 ), supplied by the battery ( 2 . 1 ) and in connection with a charge and command control ( 4 . 1 ), generates electric pulses which through a pulse modulation system ( 4 . 1 ) and a safety control system ( 4 . 3 ) are transmitted to the electrodes ( 1 . 2 ), ( 1 . 3 ) and the third conductor ( 1 . 4 ). Said electrodes and conductor are then used to charge the battery ( 2 . 1 ).
In a preferred embodiment, said vaginal stimulate is provided with a carrying and control case.
The carrying and control case may have a rectangle parallepipede shape and comprises a main body with a cover, which may be together joined by a hinge. Said case has, for example, the following dimensions: 10 centimeters long, 10 centimeters wide and 5 centimeters high. It is divided in two parts: the main body ( 3 ) which may be 10 centimeters long, 10 centimeters wide and 4 centimeters high and the cover (not represented) which may have, for example, the following dimensions: 10 centimeters long, 10 centimeters wide and 1 centimeter high.
The main body includes the following elements illustrated on FIG. 3 :
1. A transformer with charge circuitry located in compartiment ( 3 . 1 ) of the main body which receives equally input current of 110 or 220 volts and will transform it in an adequate output current able to charge the inside vaginal stimulator rechargeable battery for example in 4 to 6 hours.
2. A power cord ( 3 . 2 ) to link the transformer to the supply area. This power cord is located in compartiment ( 3 . 3 ) and is directly connected to the transformer. The power cord can be easily gotten out of its location ( 3 . 3 ) to be connected with the mains supply. Once the power cord out of its location and the power cord location cover ( 3 . 5 ) closed, the power cord will be hold in a passage ( 3 . 4 ) and the cover of the carrying and control case can be closed.
3. An electronic control system (not represented) permitting to the device user, through the two control knobs ( 3 . 6 ), ( 3 . 7 ) and the carrying and control case cover, to transmit orders to the vaginal stimulator microcontroller or to recharge the inside vaginal stimulator rechargeable battery.
4. Control knob ( 3 . 6 ) permits to the device user to select the type of urinary incontinence: urge incontinence ( 3 . 8 ) or stress incontinence ( 3 . 9 ). The urge incontinence position ( 3 . 8 ) corresponds to 12.5 Hz pulse frequency and the stress incontinence position ( 3 . 9 ) corresponds to 50 Hz pulse frequency coming from the inside vaginal stimulator microcontroller. The orders given by the device user through this control knob ( 3 . 6 ) are sent to the electronic control system of the carrying and control case.
5. Control knob ( 3 . 7 ) permits to the device user to select the use time of the vaginal stimulator: 15 minutes ( 3 . 10 ), 30 minutes ( 3 . 11 ), 45 minutes ( 3 . 12 ) or 60 minutes ( 3 . 13 ). The orders given by the device user to the control knob ( 3 . 7 ) are sent to the electronic control system of the carrying and control case.
6. A green control light ( 3 . 14 ) which indicate to the device user that the inside vaginal stimulator rechargeable battery is fully charged and that the vaginal stimulator can be used. When this green control light ( 3 . 14 ) is on, the red control light ( 3 . 15 ) is off
7. A red control light ( 3 . 15 ) which indicates to the device user that the inside vaginal stimulator rechargeable battery is always in charge and that the vaginal stimulator cannot yet be used. When this red control light ( 3 . 15 ) is on, the green control light ( 3 . 14 ) is off.
8. A housing ( 3 . 16 ) wherein the vaginal stimulator ( 1 . 1 ) can be put between each use. Said housing has the same shape than the vaginal stimulator but a slight upper size to permit to the vaginal stimulator to fit easily into the housing. The bottom of housing ( 3 . 16 ) comprises three metal contacts ( 3 . 17 ), ( 3 . 18 ), ( 3 . 19 ) intended for transmitting to the three vaginal stimulator conductors (FIG. 1 : ( 1 . 2 ), ( 1 . 3 ), ( 1 . 4 )), orders coming from the electronic control system and given by the device user through the control knobs ( 3 . 6 ), ( 3 . 17 ) or through the carrying and control case cover. A wedge ( 3 . 20 ) is provided at one end of the housing ( 3 . 16 ) and is adapted to fit into the vaginal stimulator eyelet ( 1 . 5 )) when the vaginal stimulator is put into the housing ( 3 . 16 ). The wedge ( 3 . 20 ) is intended to maintain the vaginal stimulator in its location and to secure that the three metal contacts ( 3 . 17 ), ( 3 . 18 ), ( 3 . 19 ) of the housing ( 3 . 16 ) be in connection with the three vaginal stimulator conductors ( 1 . 2 ), ( 1 . 3 ), ( 1 . 4 ) when the vaginal stimulator is in the housing.
9. A string spool niche ( 3 . 21 ) with a cover ( 3 . 22 ) intended to keep a string spool ( 3 . 23 ). A cutting system ( 3 . 24 ) is provided with the string pool niche to cut the string before the use or after the use of the vaginal stimulator.
10. In the hinge joining the cover to the main body of the carrying and control case there is a switch which gives orders to the electronic control system. The opening of the cover stops automatically the charge of the inside stimulator rechargeable battery and starts the working of the vaginal stimulator, when the vaginal stimulator is in its housing. The closing of the cover stops automatically the working of the vaginal stimulator and starts the charge of the inside vaginal stimulator rechargeable battery, when the vaginal stimulator is in its housing.
The block diagram of the inside carrying and control case electronic control system is given on FIG. 4 B. The charge circuit ( 4 . 4 ) receives input current of 110 or 220 volts which is transmitted through the command control ( 4 . 5 ) to the metal contacts of the housing.
Advantageously, the device of the invention is free from cable linking the carrying and control case to the vaginal stimulator and is then pratical to use.
Prior the first use, the device user has only to select the type of incontinence and the wished use time. He has also to make a first charge of the inside vaginal stimulator rechargeable battery (6 hours). To use the vaginal stimulator there is only to open the carrying and control case, remove the vaginal stimulator from its housing, thread a 20 centimeters bit of string in the eyelet, knot the two ends of the string, lubricate the vaginal stimulator and insert it into the vagina. The vaginal stimulator is working. At the end of the session, take the vaginal stimulator out of the vagina, cut and throw away the bit of string, clean the vaginal stimulator, place it back in its resting nest and close the cover of the carrying and control case. The battery will be charge automatically. | A vaginal applicator-stimulator system includes a body having a first set of conductors for transmitting electrical pulses to the vagina. A battery power supply is located inside the stimulator body and a micro-controller is located in the stimulator body for controlling the application of pulsating signals to the first set of conductors in accordance with programmed instructions corresponding to a particular type of urinary incontinence to be treated. A case is included for enclosing the cylindrical stimulator body during non-use of the stimulator body, the case having-contacts correspondingly aligned with the conductors of the stimulator body. An apparatus is located in the case for entering instructions regarding current to be applied by the first set of conductors of the stimulator body that stimulate according to the type of urinary incontinence to be treated. The micro-controller in the stimulator body stores the entered instructions. | 0 |
This invention concerns riding figure toys commonly referred to as rocking horses, in which the figure of a horse (or other animal) is supported on rockers and adapted to be mounted by a child so as to be ridden. Such a toy is typically a childhood favorite of young children for most of their early years.
The ability to use a rocking horse over several periods during a child's development from infancy would increase its appeal. Such extended period of use could be realized if the rocking horse could be convertible from a cradle, as it could be employed initially for the child as an infant, as a rocking horse as the child grows older, and later by the child as a cradle for dolls. This extended period of use would justify the expense of a quality constructed rocking horse.
In U.S. Pat. No. 267,678 there is disclosed a rocking horse convertible from a cradle configuration, but the arrangement shown therein describes rocking of the infant in a lengthwise direction contrary to the usual sideways cradle rocking motion.
Also, since vigorous riding activity must be anticipated, the construction of a rocking horse must be sturdy and well designed to mimimize injuries.
SUMMARY OF THE INVENTION
The present invention comprises a riding horse or other riding figure toy which is readily convertible between riding and cradle configurations. A riding figure is attached to an intermediate pivot platform which in turn is mounted to a rocker assembly so as to be oriented in either of two rotated positions. In a first position the riding figure is disposed lengthwise parallel to the rockers, for conventional use with a child astride a saddle portion of the figure.
In a second rotated position the figure is disposed transversely to the rockers. A saddle portion is removable from the figure to create a cradle cavity, which is thereby disposed transversely to the rockers, enabling side-to-side conventional cradle rocking action. This enables use of the rocking toy both in the infancy of a child as a cradle and later as a cradle for the child's play use with dolls.
This removable saddle portion preferably takes the form of a compartmented miniature play chest, itself separately usable and when in position affords a fail safe preventive against covering the cradle cavity with an infant within.
The intermediate pivot platform is generally in rectangular form with angled corners, which wedge beneath complementarily shaped locking features formed on the rocker assembly in each rotated position, securely retaining the platform and figure on the rockers in each position. A locking pin is insertable to fix the platform and figure in either rotative position.
A cut out in either side of the platform provides a step to facilitate mounting of the figure when used as a riding toy.
DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a convertible rocking toy according to the present invention, shown in the riding configuration.
FIG. 2 is a perspective view of the rocking toy shown in FIG. 1 in le orientation of the platform and figure.
FIG. 3 is a plan view of the rocking toy shown in FIG. 1 with the configuration shown in phantom.
FIG. 4 is an exploded perspective view of the rocking toy shown in FIGS. 1-3 illustrating the major components thereof.
FIGURE 5 is a transverse sectional view of the rocking toy shown in FIGS. 1-4 illustrating details of the pivot and locking pin associated with the intermediate platform.
DETAILED DESCRIPTION
In the following detailed description, certain specific terminology will be employed for the sake of clarity and a particular embodiment described, but it is to be understood that the same is not intended to be limiting and should not be so construed inasmuch as the invention is capable of taking many forms and variations within the scope of the appended claims.
Referring to FIG. 1, the rocking toy 10 according to the present invention includes a horse riding FIG. 12 supported on outwardly inclined legs 14 above an intermediate platform 16.
The horse riding FIG. 12, could of course represent other animals or objects, and has an elongated body portion 18, here provided by a barrel shaped structure. This body portion 18 provides a ridable support for a child seated astride a saddle surface 20. The child may grasp the mane 22 or suitable handles 24 extending from the head 26 attached to the body 18 in conventional fashion. Retractable foot rests 27 may also be provided, slidably received in sockets extending from the body 18.
The platform 16 is supported on a rocker assembly 28, the assembly including a pair of laterally spaced rockers 30 connected by a crosspiece 32 fixed to each rocker 30.
The intermediate platform 16 is generally square in shape and each corner 34 is shaped with an angled surface 36 which wedges beneath a complementary mating surface 38 formed at the ends of recesses 40 let into the top of each rocker 30. This draws the platform 16 and attached riding FIG. 12 tightly to the rocker assembly 28 to prevent any looseness of the platform 16 and FIG. 22 on the rocker assembly 28 and prevents dislodgement thereof.
A cutout 42 in either side of the platform creates a step up for easier mounting of the riding FIG. 12, when configured as a rocking horse and affords a toe clearance when in the cradle configuration.
The riding FIG. 12, in the orientation shown in FIG. 1, extends parallel to the rockers 30 for conventional rocking horse action.
FIG. 2 shows the riding FIG. 12 and platform 16 rotated on the rocker assembly 28 to extend transversely to the rockers 30 preparatory to conversion to a cradle. In this orientation, the corners 34 of the platform 16 likewise wedge beneath the surfaces 38 and the rocker recess 40. The handles 27 may be retracted into the sockets 29, to be out of the way as shown.
This rotation of the riding FIG. 12 is shown in FIG. 3.
The saddle 30 may be removed as shown in FIG. 4 to enable access to a cradle cavity 44 formed extending along and within the elongated body portion 18 of the riding FIG. 12. As also seen in FIG. 4, the saddle 30 is preferably formed as the top of a structure 46 which fills the cradle cavity 44, so as to prevent the cavity 44 from being occupied when the saddle 30 is in place. The structure 46 may advantageously take the form of a miniature compartmented storage chest having drawers 48 and a mirror 50, usable as a separate play item.
Vent openings 52 may also be provided extending into the cradle cavity 44 adding an additional safety feature in the event a small child or infant is placed in the cavity 44 and the saddle area covered.
The riding FIG. 12 and attached platform 16 are pivotably mounted onto the rocker assembly 28 by a pivot tube 52 extending upwardly from the crosspiece 32. The pivot tube 52 is received in a bore 54 formed in the platform 16 to enable rotation of the platform on the rocker assembly 28 about a fixed axis.
A locking pin 56 is received in the platform 16 which can be inserted in mating holes 58 located to fix the platform 16 in either transverse or longitudinal orientation with respect to the rocker assembly 28, as seen in FIG. 5.
The various components may be constructed of molded plastic as shown in FIG. 5, or solid plastic or wooden parts, are other alternate construction as desired.
Similarly, the pivoting action may be provided by various alternate mechanical arrangements.
Accordingly, the riding toy as described may be used as a cradle by a simple convertible action, and is of interest to small children of all ages, so that it is useful over an extended period of a child's life.
The construction is simple and rugged, and its design offers security against injury caused by the mishaps to be expected. | A rocker toy convertible from a riding rocker to a cradle use by orienting a intermediate platform in either of two rotative positions on a rocker assembly, disposed lengthwise or transversely to the rocking direction. A removable saddle-closure is attached to a miniature chest separately usable as a play item. The platform securely locks to a crosspiece included in the rocker assembly in either rotative position. | 0 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to the field of artificial dentures, and more particularly, to such dentures prepared from polyurethane elastomers and hard polymer components such as the hard acrylic resins and the hard epoxide resins.
2. Description of the Prior Art
It has been proposed to provide dentures with a soft layer in contact with the gums and other mouth parts to provide tissue relief. Such soft layers have been composed of acrylics, silicones, and similar rubber-like materials. But on aging, such soft layers tend to harden and give off undesirable odors. In addition, some decomposition of the polymer may also occur presumably due to an oxidation process as well as to pH fluctuations within the mouth. By way of overcoming these disadvantages, U.S. Pat. Nos. 4,024,636 and 4,080,412, both to Colpitts et al., and both incorporated by reference herein, describe dentures in which teeth are anchored in a gum member comprising a tooth-holding portion fabricated from a hard nonhydrophilic polyurethane elastomer having a hardness of not less than about Shore D40, and a mouth-engaging portion fabricated from a soft nonhydrophilic polyurethane elastomer having a hardness of not greater than about Shore A65 integrally and chemically bonded into a unitary mass. U.S. Pat. No. 4,024,637 to Colpitts which is also incorporated by reference herein describes a denture in which hard non-hydrophilic polyurethane elastomer teeth are imbedded in and chemically bonded to a soft non-hydrophilic polyurethane elastomer. Preferred non-hydrophilic elastomers are those formed by isocyanate-terminated prepolymers which are cross-linked or cured by mixing with a cross-linking agent and heating as required to effect curing. Isocyanate-terminated prepolymers suitable for preparing the hard non-hydrophilic polyurethane elastomers are prepared by the reaction of polyether diols or triols with aliphatic or cycloaliphatic or aralkyl di- or polyisocyanates in proportion to give free NCO groups. The prepolymers are then cured or cross-linked with a diol, polyol, an alkanolamine, a diamine or a tertiary amine containing polyol, or blends thereof. Advantageously, the diol or polyol is a polyether diol or polyol or a hydroxyl-terminated prepolymer.
By way of improving the resistance of polyurethane dentures to mechanical distortion or flex under the conditions prevailing in the mouth, U.S. Pat. No. 4,225,696 to Colpitts, et al., which additionally is incorporated by reference herein, substitutes the aforementioned aliphatic, cycloaliphatic or aralkyl di- or polyisocyanates with aromatic polyisocyanates in which the isocyanate groups are bonded directly to the aromatic nucleus, e.g., 2,4-tolylene diisocyanate (TDI), isomeric mixtures of TDI, 3,3'-tolidene 4,4'-diisocyanate (TODI), 3,3'-dimethyldiphenylmethane 4,4'-diisocyanate, diphenylmethane 4,4'-diisocyanate (MDI), mixtures of MDI and adducts of MDI, etc. The resulting polyurethane can be fabricated into the soft, mouth-engaging portion of a denture possessing a relatively hard polymer as the tooth-engaging portion thereof. The hard polymer can be a hard polyurethane prepared in accordance with any of the aforesaid Colpitts, et al., patents or it can be any of the hard polymers heretofore used in the making of dentures. As is well known, the acrylics, a class of relatively hard resins, have for many years been used in the manufacture of prosthodontic devices and would be prime candidates for preparing composite polyurethane/hard polymer dentures in accordance with the teachings of U.S. Pat. No. 4,225,696 to Colpitts, et al. However, as desirable an improvement as such composite dentures are, their polyurethane components which, as previously stated, are prepared from an aromatic isocyanate such as TDI, TODI or MDI, are relatively photosensitive and prone to degradation by actinic radiation. The probable explanation of this behavior is that when an isocyanate group reacts with water, it forms a urea group which, in the case of the aromatic isocyanates, is relatively chemically stable but light sensitive.
Accordingly, it is desirable to provide a denture which has a soft, mouth-engaging element to provide for the wearer's comfort and which at the same time is resistant to flex and photodegradation.
SUMMARY OF THE INVENTION
In accordance with the present invention, an artificial denture of composite construction is provided which comprises a tooth-holding portion fabricated from a hard non-polyurethane polymer having a hardness of not less than about Shore D40 integrally chemically bonded to a mouth-engaging portion fabricated from a soft non-hydrophilic polyurethane elastomer having a hardness of not greater than about Shore A65, said polyurethane being the reaction product of a polyether polyol and an aliphatic, cycloaliphatic or aralkyl di- or polyisocyanate in which the isocyanate groups are directly bonded to the aliphatic, cycloaliphatic or alkyl moieties thereof.
The composite dentures of the present invention possess significant advantages over an all-polyurethane denture. Approximately 40% of all full and partial dentures currently being made possess acrylic teeth. Since in practice it is difficult to obtain a good chemical bond between acrylic teeth and polyurethane, the opportunities for debris (derived from foods, beverages, tobacco, etc.) to infiltrate crevices between the teeth and the polyurethane are much greater than in the case of acrylic teeth bonded to an acrylic tooth-holding portion. And since the hard acrylics as a class are generally quite stable to flex and are superior in this regard to an all-polyurethane denture whose mouth-engaging portion is prepared with an aliphatic, cycloaliphatic or aralkyl di- or polyisocyanate, it is particularly advantageous to mate the relatively flex-prone but photodegradation resistant soft polyurethanes as aforedescribed with the acrylics or, for that matter, with any other flex-resistant nonpolyurethane polymers such as the hard epoxide resins. The resistance of such polyurethanes to degradation under the influence of actinic radiation is probably due to the fact that unlike aromatic urea groups, the aliphatic urea groups of these polyurethanes (to the extent formed by reaction of some isocyanate groups with water) tend to react with each other to form biuret which is considerably more light resistant than aromatic urea groups which do not react to provide biuret in any appreciable amount. Yet another advantage of these polyurethanes over those prepared with aromatic isocyanates lies in the reduced incidence with which they form urea/biuret groups at all. More of the available isocyanate groups of an aliphatic isocyanate will react with the hydroxyl groups of the polyether polyol to form the desired urethane linkages (which confer chemical resistance) than would be the case with an aromatic isocyanate.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The tooth-holding portion of the composite denture herein can be prepared from among any of the known and conventional hard acrylic resins employed in the manufacture of dentures, e.g., those having a hardness of at least Shore D40 and up to about Shore D100. The term "acrylic resin" as used herein is intended to include homopolymers of acrylic esters and acrylic amides of the general formula ##STR1## in which X is O or NH, R 1 is H or methyl and R is any of a wide variety of groups including aliphatic, cyclocloaliphatic, alkaryl, aralkyl, alkoxy, aryloxy, glycidyl, etc., groups, and copolymers of said esters/amides with other acrylic esters/amides and/or with one or more other copolymerizable ethylenically unsaturated monomers such as acrylonitrile, butadiene, styrene, vinyl acetate, and the like. Poly(methylmethacrylate) is an especially preferred resin for the tooth-holding portion of the composite denture herein because of the ready availability of the monomer, its low cost and its common use in dentistry. The techniques whereby acrylic resins can be fashioned into denture and partial dentures are well known, e.g., U.S. Pat. Nos. 3,251,910 and 3,258,509 to Barnhart both of which are incorporated by reference herein.
The hard epoxide resins, e.g., those having a hardness of at least Shore D40 and up to about Shore D100, which can be employed as the teeth-holding component of the dentures herein constitute a well known class of thermosetting resins. Representative of these resins are those derived from bisphenol A and epichlorohydrin cured with any of a variety of polyamines and specialty epoxy resins such as epoxy cresol novolac resins, epoxy phenyl novolac resins, bisphenol F-derived resins, polynuclear phenol-glycidyl ether-derived resins, cycloaliphatic epoxy resins, aromatic and heterocyclic glycidyl amine resins, tetraglycidylmethylenedianiline-derived resins, triglycidyl-p-aminophenol-derived resins, triazine-based resin and hydantoin epoxy resins. Details of the formulation of hard epoxide polymer-forming compositions and the conditions under which they undergo polymerization are well known matters to those skilled in the art and are fully described in the literature, e.g., Kirk-Othmer Encyclopedia of Chemical Technology, Third Edition, Vol. 9, pp. 274 et seq., John Wiley & Sons, Inc. which is incorporated by reference herein. The polyether polyols which can be used in preparing the mouth-engaging soft polyurethane portion of the composite denture herein can be selected from amongst any of the polyether polyols heretofore employed in the preparation of polyurethanes. Such polyols possess two, and preferably, three or more hydroxyl groups. Among the useful polyether polyols are included the poly-(oxypropylene) glycols, the poly-(oxypropylene) poly-(oxyethylene) glycols, the poly-(1,4-oxypropylene) glycols and graft copolymers of the poly-(oxypropylene) (polyoxyethylene) glycols with acrylonitrile or mixtures of acrylonitrile and styrene. The equivalent weight of these polyether diols can range between 200 to 100 with a preferred range of 200 to 400. The polyol may consist of simple polyfunctional alcohols such as glycerine, trimethylolpropane, 1,2,6-hexanetriol, or pentaerythritol, or they may consist of polyether triols such as poly(oxypropylene) or poly(oxyethylene) adducts of the above polyols. The equivalent weight of the polyether polyols may range between 100 to 800 with a preferred range of 100 to 500. It is also understood that various combinations of diols and polyols may be used.
The polyisocyanates used for the preparation of the soft polyurethane elastomers must contain the isocyanate groups directly bonded to the aliphatic moieties thereof. Such isocyanates include, but are not limited to 4,4'-Dicyclohexylmethane diisocyanate, isophorone diisocyanate, 2,2,4-trimethyl-1,6-hexane diisocyanate, hexamethylene diisocyanate, xylylene diisocyanate, "dimeryl" diisocyanate, methylcyclohexyl diisocyanate and the reaction product of 3 moles of hexamethylene diisocyanate with one mole of water (Desmodur N-triisocyanate).
The ratio of NCO to OH in the preparation of the soft isocyanate-terminated prepolymer may range between 1.75 to 2.5 with a preferred range of 2.0 to 2.25. The soft isocyanate-terminated prepolymers should have a free NCO content of about 3.5 to 5.5 percent, preferably, 3.7 to 4.7 percent.
For curing (crosslinking) of the prepolymers, preferred polyols are tertiary amine-containing polyols such as poly(oxypropylene) or poly(oxyethylene) adducts of diamines or triamines, such as ethylenediamine, diethylene triamine, tolylenediamine, phenylenediamine, or aniline, or any diols, polyols or their blends. Advantageously, they are polyols of relatively low molecular weight such as are obtained by condensing propylene oxide with ethylenediamine or pentaerythritol to a molecular weight of about 500, or of trimethylolpropane or any other base compound to a molecular weight up to 2500.
Another preferred curing or crosslinking agent is a hydroxyl-terminated prepolymer. These are prepared essentially the same way as the isocyanate-terminated prepolymers but the ratio is such that there are free and un-reacted hydroxyl groups. The same diols and polyol and isocyanates can be used, though it is preferred that the prepolymer have a functionality greater than 2, which can be obtained by using a polyol having a functionality greater than 2 and/or an isocyanate having a functionality greater than 2. Advantageously, the isocyanate is 2,2,4-trimethyl-1,6-hexane diisocyanate, hexamethylene diisocyanate or Desmodur N.
The ratio of OH/NCO in the hydroxyl-terminated prepolymers advantageously may be in the same range as the NCO/OH ratio in the isocyanate-terminated prepolymers. It will be understood, however, that inasmuch as the crosslinking agent may consist of one or more diols or polyols (no isocyanate), the ultimate OH/NCO ratio is infinity.
Another preferred curing or crosslinking agent is a prepolymer-polyol blend. Thus, a polyurethane prepolymer, advantageously, one having neither free NCO nor free OH groups, can be mixed with a polyol, advantageously a polyol having a functionality of more than 2, to form a prepolymerpolyol blend. When such a blend is mixed with an isocyanate-terminated prepolymer in an NCO/OH ratio of greater than 1, crosslinking is effected both through an NCO-OH reaction and through an NCO-urethane reaction.
To join the hard polymer component to the soft polyurethane component, one or both adjoining surfaces is coated with a primer formulation prepared by mixing polyisocyanate with polyol and thereafter the two components are joined. Upon curing of the soft elastomer formulation, a denture will be provided in which the hard and soft elements are permanently bonded to each other.
In order to accelerate the formation of the prepolymers or the cure of the prepolymers with the cross-linking agents, metal catalysts such as tin catalysts, for example, dibutyltin dilaurate and stannous octanoate, can be used.
In the following soft polyurethane resin formulations (all parts by weight) which are illustrative of the invention herein, the ingredients whose properties are given in the Table below were employed.
I. PREPARATION OF PREPOLYMERS (COMPONENTS A)
______________________________________FORMULATION I______________________________________Polymeg 1000.sup.1, 4 moles × 976 = 3904Polymeg 2000.sup.2, 1 mole × 1998 = 1998Hylene W.sup.3, 10 moles × 262 = 2620Dibutyltin dilauratecatalyst 1.7 8523.7Equivalent weight per one NCO 852.4______________________________________ .sup.1 Poly (oxytetramethylene) glycol; Mol. wt. 976 .sup.2 Poly (oxytetramethylene) glycol; Mol. wt. 1998 .sup.3 4,4dicyclohexylmethane diisocyanate
PREPARATION PROCEDURE
Polymeg 1000 and Polymeg 2000 are charged into the reactor and the mixture heated to 70° C. It is demoisturized in vacuum for 2-3 hours until the evolution of bubbles ceases.
Afterwards a dry nitrogen blanket is applied and the mixture is cooled to 50° 0C. and Hylene is added. The reaction mixture is stirred at 100-120 rpm for at least 30 minutes and watched, for a slight exothermic reaction may ensue. The temperature of the reactor is maintained at 65°-70° C. The catalyst is added in portions in order to speed up the reaction. After 3 hours have elapsed the NCO content is checked using the n-dibutylamine titration method. The NCO content should be in the range of 4.8%. The variation here and elsewhere may be ±5 percent.
When this level of free NCO is reached, the contents of the reactor are cooled and are packaged into one gallon or one quart lined containers. Dry nitrogen is used to maintain an inert atmosphere in the containers which are then tightly closed.
______________________________________FORMULATION 2______________________________________Polymeg 1000, 2 moles × 976 = 1952Polymeg 2000, 1 mole × 1998 = 1998Hylene W, 6 moles × 262 = 1572Dibutyltin dilauratecatalyst 1.1 5523.1Equivalent weight per one NCO 920.5______________________________________
Preparation procedures are the same as in Formulation 1. The free NCO content of the prepolymer should be 4.5%.
______________________________________FORMULATION 3______________________________________Polymeg 2000, 1 mole × 1998 = 1998Polymeg 1000, 1 mole × 976 = 976Hylene W, 4 moles × 262 = 1048 4022Equivalent weight per one NCO 1005.5______________________________________
Preparation procedures are the same as in Formulation 1. The free NCO content should be 4.18%.
______________________________________FORMULATION 4______________________________________Polymeg 2000 1198Polymeg 1000 488Hylene W 786Dibutyltin dilaurate, catalyst .76 3272.76Equivalent weight per one NCO 1190______________________________________
PREPARATION PROCEDURE
Poly(oxytetramethylene) glycols, Polymeg 2000 and Polymeg 1000, are charged into a reactor and demoisturized in vacuum for 2-3 hours upon a gentle stirring of 60-120 rpm at 70° C.
The demoisturized glycol mixture is cooled down to 50° C., a dry nitrogen blanket is applied, and diisocyanate (Hylene W) is added. The catalyst is added in portions in order to speed up the reaction.
The charge of the reactor should exotherm. The temperature of the reactants should not be allowed to go over 75° C. After 2-3 hours of the reaction, the NCO content should be checked by the n-dibutylamine titration method. The NCO content should be in the range of 3.3%. If the content of NCO higher than 3.7% is found, the heating should be continued for an additional hour at 70° C. after the addition of a small amount (0.005%) of the catalyst.
The above soft isocyanate-terminated prepolymers are essentially linear.
PREPARATION OF CROSSLINKING AGENTS (COMPONENTS B)
______________________________________FORMULATION 5______________________________________Pluracol 355* 100 g.TiO.sub.2 (rutile) 0.2 g.Dibutyltin dilaurate catalyst as needed 100.2Equivalent weight per one hydroxyl 125.1______________________________________ *Poly(oxypropylene) derivative of ethylenediamine, Mol. wt. 490
PREPARATION PROCEDURE
All the pigments are dispersed in 5% of the total polyol, Pluracol 355. For dispersion purposes a ball mill or roller mill or any well-dispersing high speed mill can be employed.
Then all of the remainder of the polyol, Pluracol 355, is stirred in. Afterwards the mixture is degassed and demoisturized by applying a vacuum and gentle heating at 60°-70° C.
The catalyst has to be added before application. The amount of the catalyst depends on the type of isocyanate-terminated prepolymer to be used. Usually 0.15-0.35% of the catalyst is added, based on the total weight of the polymer and on the type of the polymer and the reacting groups.
______________________________________FORMULATION 6______________________________________1,4-Butanediol 450Pluracol PeP 550* 500TiO.sub.2 1.g.Dibutyltin dilaurate catalyst as needed 951.Equivalent weight per one hydroxyl 68.0______________________________________ *Poly(oxypropylene) adduct of pentaerythritol of about 500 molecular weight
PREPARATION PROCEDURE
All the pigments are dispersed in 5% of the polyols; then all the remainder of the polyols is blended with the pigment dispersion. Afterwards the mixture is demoisturized by applying a vacuum and gentle heating at 60°-70° C.
The catalyst has to be added before application. The amount of the catalyst depends on the type of isocyanate-terminated prepolymer to be used.
Usually for the rigid elastomer formulation the amount of the catalyst is in the range of 0.15-0.25% for the soft elastomer formulation, in the range of 0.30-0.35%.
______________________________________FORMULATION 7______________________________________Pluracol PeP 550 500 g.TiO.sub.2 0.5 500.5Equivalent weight per one hydroxyl 125.1______________________________________
Preparation procedure is similar to the procedure of Formulation 6.
______________________________________FORMULATION 8______________________________________Pluracol TP 440 420 g.Butanediol 450 g.TiO.sub.2 1 g.Dibutyltin dilaurate catalyst as needed 871.Equivalent weight per one hydroxyl 67______________________________________
Preparation procedure is similar to the procedure of Formulation 6.
______________________________________FORMULATION 9______________________________________Desmodur N - triisocyanate.sup.1 478Polymeg 650 - 2112Pluracol TP 1540.sup.2 750TiO.sub.2 5.0Yellow No. 6 Lake 3.0Red No. 3 Lake 1.8Blue No. 1 Lake 0.2 3350.0Equivalent weight per one hydroxyl 668______________________________________ .sup.1 (three moles of hexamethylene diisocyanate reacted with one mole o water) .sup.2 Poly(oxypropylene) derivative of trimethylolpropane, Mol. Weight 1500
PREPARATION PROCEDURE
Poly(oxytetramethylene) glycol is charged into a reactor and demoisturized in vacuum for 2-3 hours upon gentle stirring at 60-120 rpm at 70° C. Then the vacuum is released under dry nitrogen, and the dry nitrogen blanket is retained during the reaction time.
Desmodur N-triisocyanate is stirred in and reacted with the glycol until the NCO content is reduced to zero. Then Pluracol TP 1540 is blended in.
The pigments are dispersed in a small amount of the triol, Pluracol TP 1540, and stirred in with the total content of the prepolymer-polyol blend.
II. PREPARATION OF SOFT POLYURETHANE RESINS
EXAMPLE 1
Component A, Formulation 1, 100 parts
Component B, Formulation 5, 13.6 parts
Catalyst, stannous octoate, 8 drops
NCO/OH=1.08 to 1
Components A and B are degassed and demoisturized for at least 1 hour at 60° C. and then blended gently with the catalyst and placed in a pre-heated vacuum oven for 1-2 minutes. They are then cast into a pre-heated denture mold containing a previously cast hard-non-hydrophylic polyurethane elastomer as above described and kept in an oven at 90° C. for 3 hours. The denture is then removed from the mold and finished by removing the sprues and flash and polishing as necessary.
EXAMPLE 2
Component A, Formulation 2, 100 parts
Component B, Formulation 6, 7 parts
Catalyst, dibutyltin dilaurate, 12 drops
NCO/OH=1.05 to 1
EXAMPLE 3
Component A, Formulation 3, 100 parts
Component B, Formulation 6, 6.44 parts
Catalyst, dibutyltin dilaurate, 16 drops
NCO/OH=1.05 to 1.
The compositions of Examples 2 and 3 are degassed, demoisturized, blended, cast, and cured as in Example 1.
EXAMPLE 4
Component A, Formulation 9, 100 parts
Component B, Formulation 11, 56.2 parts
Catalyst, stannous octoate, 0.32
NCO/OH=1.05 to 1.
Components A and B should be heated up to approximately 60° C. and degassed and demoisturized under vacuum before blending. Then the catalyst should be added. The blend should be cast into a preheated mold and heated with a mold release agent. The elastomer should be cured in an oven at 95° C. for 2 hours.
IV. MANUFACTURE OF COMPOSITE DENTURE
EXAMPLE 5
In this example, a pre-formed hard acrylic denture supplied by a dental laboratory or dentist is provided with a mouth-engaging portion prepared with a soft polyurethane elastomer such as any of those described in Examples 1 to 4 above.
The hard acrylic denture is placed in a flask such that the lowest portion of the denture is even with the flask. Investment material is then introduced into the flask even with the top of the flask. After the investment has set-up, a mold release agent is applied to all surfaces, i.e., investment, denture and teeth. After the mold release agent has dried (approximately five minutes), additional investment material is applied to cover the entire denture. The flask is then completely sealed by fastening a lid thereon. The flask is separated and the denture removed. The denture is then ground out to provide room for the soft polyurethane elastomer mouth-engaging portion.
Upon receipt of a conventional, complete acrylic denture with a new rebase impression taken by a dentist, a plaster model is prepared in accordance with conventional dental laboratory procedures. Thereafter, the plaster model is sealed (i.e., a coating is placed on all exposed plaster surfaces except the bottom). The denture is then placed in a flask such that the lowest portion of the denture is even with the flask. Investment material is then introduced into the flask even with the top of the flask. After the investment has set-up, a mold release agent is applied to all surfaces, i.e., investment, denture and teeth.
After the primer or mold release agent has dried (approximately five minutes), additional investment material is applied to cover the entire denture. The flask is then completely sealed by fastening a lid thereon. The flask is separated and the denture removed. The denture is then ground out to provide room for the soft polyurethane elastomer. Sealer is again applied to all newly exposed plaster surfaces. Following the grinding out of the denture, the denture is washed with anhydrous isopropanol or ethanol to remove grinding residue and air-dried. A primer, e.g., 7.8 g Pep 550 (a polyether polyol from BASF Wyandotte having an average molecular weight of about 600 and a hydroxyl number of 448 and which is based on pentaerythritol oxyalkylated with propylene oxide) mixed with 7.3 g Hylene W (DuPont's 4,4'-dicyclohexylmethane diisocyanate) is applied to all surfaces of the denture where the soft elastomer is to adhere. The blockout material is removed from the plaster model. Mold release is again applied to the mold and plaster model and permitted to air-dry (approximately five minutes). The primed denture is then inserted in the mold cavity. Liquid soft polyurethane formulation is introduced into the mold cavity and low spots on the plaster mold. The entire mold assembly is placed in a clamp and the clamped mold is placed in an oven heated to 85° C. After about three hours, the assembly is removed from the oven and cooled until comfortable to the touch. The mold is opened and the denture is removed from the investment and plaster model. The denture is thereafter trimmed, polished, etc., to provide the finished product.
It is to be understood that the invention is not to be limited to the exact details of operation or structure shown and described as obvious modifications and equivalents will be apparent to one skilled in the art. | An artificial denture of composite construction is provided which comprises a tooth-holding portion fabricated from a hard non-polyurethane polymer having a hardness of not less than about Shore D40 integrally chemically bonded to a mouth-engaging portion fabricated from a soft non-hydrophilic polyurethane elastomer having a hardness of not greater than about Shore A65, said polyurethane being the reaction product of a polyether polyol and an aliphatic, cycloaliphatic or aralkyl di- or polyisocyanate in which the isocyanate groups are directly bonded to the aliphatic, cycloaliphatic or alkyl moieties thereof. | 0 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to provisional application Serial No. 60/392,667, filed Jun. 28, 2002. This application is also related to provisional application Serial No. 60/391,737, filed Jun. 26, 2002, and entitled “Stent-Graft Fastening Arrangement.”
TECHNICAL FIELD
[0002] This invention relates to a device for the deployment of a stent graft within the aorta and particularly in relation to deployment within the thoracic aorta.
BACKGROUND OF THE INVENTION
[0003] Throughout this specification when referring to deployment of a stent graft or prosthesis within the aorta of a patient the term proximal will be used for that end of both the deployment device and the stent graft at that end which is closer to the heart of a patient and the term distal will be used for that end of the deployment device or stent graft which in use is furthest from the heart. When applied to other vessels corresponding terms such as caudal and cranial should be understood.
[0004] Deployment of stent grafts within the thoracic aorta using an endovascular deployment method through the iliac arteries into the aorta can be done with a deployment device which has retained on it a stent graft which includes an exposed stent at the distal end of the graft.
[0005] As the stent graft has in one embodiment an exposed stent at the distal end preferably with barbs on it, it must be deployed in a device which keeps the barbs covered until deployment is required. This can be done with a capsule, which covers the exposed stent, but there is a problem. When withdrawing the capsule, a proximal end retention system, which uses trigger wires to retain the proximal end of the stent, can be released by pulling the trigger wires, thereby releasing part of the graft prematurely.
[0006] It is the object of this invention to provide a deployment device which overcomes this problem or at least provides the physician with a useful alternative device.
SUMMARY OF THE INVENTION
[0007] In one form therefore although this may not necessarily be the only or broadest form the invention is said to reside in a stent graft deployment device which holds a stent graft in a retained condition and is arranged to release a distal end of a stent graft before a proximal end of the stent graft, the device having a proximal stent graft end release mechanism and a distal stent graft end release mechanism associated with a deployment catheter and an arrangement to allow movement of at least part of the deployment catheter including the distal stent graft end release mechanism independent of movement of the proximal stent graft release mechanism.
[0008] It will be seen that by this method, movement of the deployment catheter, which enables release of the distal end of the stent graft, can be achieved without movement of the trigger wire release mechanism.
[0009] Preferably the deployment catheter includes a capsule engaging the distal end of the stent graft or prosthesis or a distally extending exposed stent on the stent graft or prosthesis.
[0010] The trigger wires may be used for both the proximal end and the distal end of the prosthesis or stent graft with separate trigger wire release mechanisms for each. The trigger wire release mechanism for the distal end is actuated before removing the distal exposed stent capsule.
[0011] There may be provided a sheath over the deployment catheter to cover the stent graft during initial deployment with the sheath manipulator fixed onto the deployment catheter. Movement of the sheath manipulator on the deployment catheter will move the sheath with respect to the deployment catheter and expose the stent graft.
[0012] The arrangement to allow movement of the deployment catheter independently of movement of the trigger wire release mechanism may include a fixed handle associated with the trigger wire release mechanism and to which the trigger wires are fixed and a sliding handle to which the deployment catheter and the capsule are fixed. The sliding handle is preferably mounted on the fixed handle and can slide with respect to it from a position where the capsule on the deployment catheter covers the exposed stents at the distal end of the stent graft to a position where the exposed stents are released. Hence moving the sliding handle with respect to the fixed handle moves the deployment catheter and the capsule without releasing the trigger wires for the proximal end of the stent graft.
[0013] There may be an arrangement which prevents movement of the sliding handle with respect to the moving handle until this movement is required. This arrangement may be provided by a thumbscrew fixed to the sliding handle which engages against a portion of the fixed handle to prevent inadvertent or early movement of the sliding handle with respect to the fixed handle. The thumbscrew is removed when it is desired to move the sliding handle.
[0014] There may also be provided a mechanism which prevents the deployment catheter from being moved forward after an initial movement back. Such a mechanism may be provided by a spring loaded pin or plunger mechanism on one of the handles which engages the other of the handles and allows movement from the position where the capsule on the deployment catheter is engaged onto the exposed stents to a position where the deployment catheter is disengaged and at that time the spring loaded pin mechanism engages a recess in the other handle portion to prevent forward movement again.
[0015] There may be provided a hemostatic seal associated with the sliding handle to prevent loss of blood through the sliding mechanism. The hemostatic seal may include a guide tube fixed onto the deployment catheter and sliding into a central lumen in the fixed handle with an O ring around it to seal.
[0016] The stages of operation of a deployment device are as follows. First once the deployment device is deployed in the correct position within the anatomy of the human or animal the sheath is withdrawn to expose the stent graft. At this stage the proximal end of the stent graft is retained by mooring loops actuated by a trigger wire and the distal end of the stent graft is retained by a capsule and a trigger wire.
[0017] In an alternative form the invention is said to reside in a stent graft deployment apparatus comprising a deployment catheter having a proximal end adapted to be introduced into a patient and a distal end adapted to remain outside a patient, the distal end including a handle arrangement, the catheter having at a proximal end thereof a region adapted in use to contain a stent graft; a sheath arrangement adapted in use to extend over and cover the region adapted to be moved with respect to the catheter to expose the region to thereby enable deployment of the stent graft; a nose cone dilator positioned at the proximal end of the deployment catheter; a distal retention arrangement for the stent graft at a distal end of the region and comprising a proximally facing capsule having a passageway and adapted to retain the distal end of a stent graft; the handle arrangement including a fixed handle and a sliding handle, at least the capsule being affixed to the sliding handle, whereby movement of the sliding handle with respect to the fixed handle moves the capsule independent of movement of the nose cone dilator.
[0018] In a further form the invention is said to reside in a stent graft deployment apparatus comprising a deployment catheter having a proximal end adapted to be introduced into a patient and a distal end adapted to remain outside a patient, the distal end including a handle arrangement; a longitudinal lumen through the deployment catheter; a guide wire catheter extending through the longitudinal lumen and extending proximally of the deployment catheter, the guide wire catheter having a proximal end and a distal end; and the guide wire catheter being movable longitudinally and rotationally with respect to the deployment catheter; a nose cone dilator being attached to proximal end of the guide wire catheter and extending proximally thereof; a sheath arrangement adapted in use to cover at least a portion of the deployment catheter and to extend to the nose cone dilator and adapted to be moved with respect to the catheter to enable deployment of a stent graft retianed on the deployment device; a distal retention arrangement for the stent graft at a proximal end of the deployment catheter and comprising a proximally facing capsule having a passageway and adapted to retain a distal end of a stent graft; the handle arrangement including a fixed handle and a sliding handle, the deployment catheter and the capsule being affixed to the sliding handle, whereby movement of the sliding handle with respect to the fixed handle moves the deployment catheter and the capsule independent of movement of the nose cone dilator. Preferably there is a proximal retention arrangement on the guide wire catheter distal of the nose cone dilator for the proximal end of the stent graft and the proximal retention arrangement can include at least one proximal trigger wire. The proximal trigger wire can extend from the outside of the patient where it is retained by a trigger wire release mechanism on the fixed handle.
[0019] Preferably the distal retention arrangement includes an aperture extending through the capsule and a distal trigger wire extending along the deployment catheter and extendable through the aperture. The distal trigger wire can extend from the outside of the patient where it is retained by a trigger wire release mechanism on the fixed handle.
[0020] Preferably the sliding handle is mounted on the fixed handle and can slide longitudinally with respect to the fixed handle.
[0021] There can be further included a locking arrangement which prevents movement of the sliding handle with respect to the fixed handle. The locking arrangement can comprise a thumbscrew fixed to the sliding handle which engages against a portion of the fixed handle to prevent inadvertent or early movement of the sliding handle with respect to the fixed handle and wherein the thumbscrew can be removed when it is desired to move the sliding handle. There also can be a lock mechanism which prevents the sliding handle from being moved forward after an initial movement back. The lock mechanism can be provided by a spring loaded pin or plunger mechanism on one of the fixed handle or the sliding handle which engages the other of the fixed or sliding handles and allows movement of the deployment catheter from the position where the capsule on the deployment catheter is engaged onto the exposed stents to a position where the deployment catheter is disengaged and wherein at that time the spring loaded pin mechanism engages a recess in the other of the fixed or sliding handles to prevent further movement.
[0022] There can be further included a hemostatic seal associated with the fixed handle to prevent loss of blood between the fixed handle and the sliding handle. The hemostatic seal can include a guide tube fixed onto the deployment catheter and sliding into a central lumen in the fixed handle with an O-ring in the fixed handle engaging around the guide tube.
[0023] The stages of operation of deployment device are as follows. First once the deployment device is deployed in the correct position within the anatomy of the human or animal, the sheath is withdrawn to expose the stent graft. At this stage the proximal end of the stent graft is retained by mooring loops actuated by a trigger wire and the distal end of the stent graft is retained by a capsule and a trigger wire.
[0024] Next the distal trigger wire release mechanism is operated and the trigger wire release mechanism is completely withdrawn and discarded to remove the trigger wire from the distal end of the stent graft.
[0025] Next the thumbscrew on the sliding handle is released and discarded.
[0026] Next it is necessary to pull back on the deployment catheter manipulator so that the sliding handle moves with respect to the fixed handle until the spring pin engages into a recess in the fixed handle to withdraw the capsule from the distal end of the stent graft. At this stage the distal end of the stent graft is deployed. At this stage, too, the spring pin prevents any forward movement of the deployment catheter.
[0027] Next the proximal trigger wire release mechanism is withdrawn and discarded to remove the trigger wire from the proximal end of the stent graft. This releases the mooring loops and the graft is then fully deployed.
[0028] Finally the pin vice fixed to the fixed handle is released to withdraw the nose cone of the deployment device towards the capsule and then the deployment device is withdrawn.
[0029] Alternatively at this stage the sheath may be left in place and the deployment device less the sheath can be withdrawn so other devices such as an inflatable balloon to ensure complete engagement against the walls of the aorta may be deployed through the sheath.
BRIEF DESCRIPTION OF THE DRAWING
[0030] [0030]FIG. 1 shows a general external view of the deployment device according to one embodiment of this invention;
[0031] [0031]FIG. 2 shows a longitudinal cross-sectional view of the embodiment shown in FIG. 1;
[0032] [0032]FIG. 3 shows the same view as FIG. 2 but after withdrawal of the sheath;
[0033] [0033]FIG. 4 shows the same view as FIG. 3 but after activation of the sliding handle;
[0034] [0034]FIG. 5 shows a detailed longitudinal cross-sectional view of the sliding and fixed handle portion of one embodiment of a deployment device according to the invention;
[0035] [0035]FIG. 6 shows a view of the embodiment shown in FIG. 5 after withdrawal of the capsule;
[0036] [0036]FIG. 7 shows a side view of the embodiment shown in FIG. 5; and
[0037] [0037]FIG. 8 shows a side view of the embodiment shown in FIG. 6 after withdrawal of the capsule.
DETAILED DESCRIPTION
[0038] Now looking more closely at the drawings and in particular FIGS. 1 and 2, it will be seen that the deployment device generally comprises, working from the inside towards the outside, a guide wire catheter 1 which extends the full length of the device from a syringe socket 2 at the far distal end of the deployment device to a nose dilator 3 at the proximal end of the deployment device.
[0039] The nose cone dilator 3 is fixed to the guide wire catheter 1 and moves with it.
[0040] The nose cone dilator has a through bore 5 as an extension of the lumen of the guide wire catheter 1 so that the deployment device can be deployed over a guide wire (not shown).
[0041] To lock the guide wire catheter 1 with respect to the deployment device in general, a pin vice 4 is provided.
[0042] The trigger wire release mechanism generally shown as 6 at the distal end of the deployment device includes a distal end trigger wire release mechanism 7 and a proximal end trigger wire release mechanism 8 . The trigger wire release mechanisms 7 and 8 slide on a portion of the fixed handle 10 . Until such time as they are activated, the trigger wire mechanisms 7 and 8 which are fixed by thumbscrews 11 and remain fixed with respect to the fixed portion of the fixed handle.
[0043] Immediately proximal of the trigger wire release mechanism 6 is a sliding handle mechanism generally shown as 15 . The sliding handle mechanism 15 generally includes a fixed handle extension 16 of the fixed handle 10 and a sliding portion 17 . The sliding portion 17 slides over the fixed handle extension 16 . A thumbscrew 18 fixes the sliding portion 17 with respect to the fixed portion 16 .
[0044] The fixed handle portion 16 is affixed to the trigger wire mechanism handle 10 by a screw threaded nut 24 .
[0045] The sliding portion of the handle 17 is fixed to the deployment catheter 19 by a mounting nut 20 .
[0046] A deployment catheter extends from the sliding handle 17 through to a capsule 21 at the proximal end of the deployment catheter 19 .
[0047] Over the deployment catheter 19 is a sheath manipulator 22 and a sheath 23 , which slides with respect to the deployment catheter 19 and in the ready to deploy situation as shown in FIGS. 1 and 2 extends from the sheath manipulator 22 forward to the nose cone dilator 3 to cover a stent graft 25 retained on the deployment device distally of the nose cone dilator 3 .
[0048] In the ready to deploy condition shown in FIGS. 1 and 2, the sheath 23 assists in retaining the stent graft 25 , which includes self-expanding stents 26 in a compressed condition. The proximal covered stent 27 is retained by a fastening at 28 which is locked by a trigger wire (not shown) which extends to trigger wire release mechanism 8 . The distal exposed stent 29 on the stent graft 25 is retained within the capsule 21 on the deployment catheter 19 and is prevented from being released from the capsule by a distal trigger wire (not shown) which extends to the distal trigger wire release mechanism 7 .
[0049] [0049]FIG. 3 shows the same view as FIG. 2 but after withdrawal of sheath 23 , and FIG. 4 shows the same view as FIG. 3, but after activation of sliding handle mechanism 15 .
[0050] In FIG. 3, the sheath manipulator 22 has been moved distally so that its proximal end clears the stent graft 25 and lies over the capsule 21 . Freed of constraint, the self expanding stents 26 of the stent graft 25 are able to expand. However, the fastening 28 still retains the proximal end of the proximal stent 27 , and the capsule 21 still retains the distally extending exposed stent 29 . At this stage, the proximal and distal ends of the stent graft 25 can be independently repositioned, although if the proximal stent 27 included barbs as it has in some embodiments, the proximal end can only be moved proximally.
[0051] Once repositioning has been done, the distal end of the stent graft 25 should be released first. This is done so that blood flow, which is from proximal to distal, cannot inflate the stent graft in a wind sock type of effect and cause migration of the stent graft during deployment. For this reason, it is desirable to release the distal end of the stent graft first, but if the capsule is moved distally, then the release mechanisms could also move, which could release the proximal end prematurely. Hence the distal trigger wire release mechanism 7 on the handle 10 is removed to withdraw the distal trigger wire. Then the thumb screw 18 is removed, and the sliding handle 17 is moved distally to the position shown in FIG. 4. This moves the capsule 21 to release the exposed stent 29 . As the fastening 28 is retained on the guide wire catheter 1 , just distal of the nose cone dilator 3 and the guide wire catheter 1 is locked in position on the handle 10 by pin vice 4 , then the proximal trigger wire release mechanism 8 , which is on the handle 10 , does not move when moving the sliding handle, deployment catheter 19 and capsule 21 so the proximal end of the stent graft 25 remains in a retained position. The proximal end of the stent graft 25 can be again manipulated at this stage by manipulation of the handle. Although if the proximal stent 27 included barbs as discussed above, the proximal end can only be moved proximally. The proximal fastening 28 can then be released by removal of the proximal trigger wire release mechanism 8 .
[0052] Now looking more closely at FIGS. 5 to 8 , the detailed construction of a particular embodiment of a sliding handle mechanism according to this invention is shown. FIGS. 5 and 7 show the sliding handle mechanism in the ready to deploy condition. FIGS. 6 and 8 show the mechanism when the deployment catheter and hence the capsule has been withdrawn by moving the sliding handle with respect to the fixed handle.
[0053] The fixed handle extension 16 is joined to the trigger wire mechanism handle 10 by screw threaded nut 24 .
[0054] The sliding handle 17 is fixed to the deployment catheter 19 by screw threaded fixing nut 20 so that the deployment catheter moves along with the sliding handle 17 . The sliding handle 17 fits over the fixed handle extension 16 and, in the ready to deploy situation, is fixed in relation to the fixed handle by locking thumbscrew 18 , which engages into a recess 30 in the fixed handle extension 16 . On the opposite side of the fixed handle extension 16 is a longitudinal track 31 into which a plunger pin 32 spring loaded by means of spring 33 is engaged. At the distal end of the track 31 is a recess 34 .
[0055] A guide tube 35 is fixed into the proximal end of the sliding handle 17 at 36 and extends back to engage into a central lumen 41 in the fixed handle extension 16 but able to move in the central lumen 41 . An O ring 37 seals between the fixed handle extension 16 and guide tube 35 . This provides a hemostatic seal for the sliding handle mechanism. The trigger wire 38 , which is fixed to the trigger wire releasing mechanism 8 by means of screw 39 , passes through the annular recess 42 between the fixed handle extension 16 and the guide wire catheter 1 and then more proximally in the annular recess 44 between the guide wire catheter 1 and the guide tube 35 and forward to extend through the annular recess 46 between the guide wire catheter 1 and the deployment catheter 19 and continues forward to the proximal retaining arrangement. Similarly the distal trigger wire (not shown) extends to the distal retaining arrangement.
[0056] A further hemostatic seal 40 is provided where the guide wire catheter 1 enters the trigger wire mechanism handle 10 and the trigger wires 38 pass through the hemostatic seal 40 to ensure a good blood seal.
[0057] As can be seen in FIGS. 6 and 8, the locking thumbscrew 18 has been removed and discarded, and as the sliding handle is moved onto the fixed handle, the plunger pin 32 has slid back along the track 31 to engage into the recess 34 . At this stage, the sliding handle cannot be moved forward again.
[0058] As the trigger wire release mechanisms 7 and 8 are on the trigger wire mechanism handle 10 , which is fixed with respect to the fixed handle 16 , then the proximal trigger wire 38 is not moved when the deployment catheter 19 and the sliding handle 17 is moved so that it remains in position and does not prematurely disengage.
[0059] Throughout this specification various indications have been given as to the scope of this invention but the invention is not limited to any one of these but may reside in two or more of these combined together. The examples are given for illustration only and not for limitation.
[0060] Throughout this specification unless the context requires otherwise the words comprise and include and variations such as comprising and including will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers. | A stent graft deployment device adapted for release of a distal end ( 29 ) of a stent graft ( 25 ) before the proximal end ( 27 ) of the stent graft ( 25 ). The arrangement ( 15 ) allows movement of at least part of the deployment catheter ( 23 ) independently of movement of a proximal end release mechanism has a fixed handle ( 16 ) associated with a trigger wire release mechanism ( 6 ) and a sliding handle ( 17 ) to which the deployment catheter and a capsule ( 21 ) are fixed. The sliding handle ( 17 ) is mounted on the fixed handle ( 16 ) and can slide longitudinally with respect to the fixed handle ( 16 ). | 0 |
BACKGROUND OF THE INVENTION
This invention relates to resid hydrotreating and, more particularly, to a feed distributor and process for feeding oil and gas to a reactor.
In the past, spiraling oil costs, extensive price fluctuations, and artificial output limitations by the cartel of oil producing countries (OPEC) have created instability and uncertainty for net oil consuming countries, such as the United States, to attain adequate supplies of high-quality, low-sulfur, petroleum crude oil (sweet crude) from Saudi Arabia, Nigeria, Norway, and other countries at reasonable prices for conversion into gasoline, fuel oil, and petrochemical feedstocks. In an effort to stabilize the supply and availability of crude oil at reasonable prices, Amoco Oil Company has developed, constructed, and commercialized extensive, multimillion dollar refinery projects under the Second Crude Replacement Program (CRP II) to process poorer quality, high-sulfur, petroleum crude oil (sour crude) and demetalate, desulfurize, and hydrocrack resid to produce high-value products, such as gasoline, distillates, catalytic cracker feed, metallurgical coke, and petrochemical feedstocks. The Crude Replacement Program is of great benefit to the oil-consuming nations by providing for the availability of adequate supplies of gasoline and other petroleum products at reasonable prices while protecting the downstream operations of refining companies.
During resid hydrotreating, resid oil (resid) is upgraded with hydrogen and a hydrotreating catalyst in a three-phase mixture of oil, catalyst, and gas bubbles to produce more valuable lower-boiling liquid products. In conventional, prior art resid hydrotreating units, resid oil (resid) and hydrogen are fed and distributed in the reactor along one side of the reactor or from opposite sides of the reactor and are not adequately mixed. This causes an imbalance of liquids (oil) and gases and poor distribution of oil in the grid comprising the bubble tray and bubble caps. Poorly mixed feeds decrease the effectiveness of hydrotreating and diminish the conversion of resid to more valuable lower-boiling liquid products.
Poorly mixed feeds of resid and hydrogen-rich gases can cause hot spots, stagnant zones, excess gas channeling, and loss of product quality. It will also cause the oil (resid) to advance (rise) further up one side of the reactor than the other and increase the maldistribution of the oil and gas feeds.
Nonuniform mixtures of resid and hydrogen-rich gases can accelerate coke formation, increase solids buildup, and plug up the grid. It can lead to premature shutdown, extended downtime, and increased frequency of maintenance and repair. Increased maintenance and repair requires additional manpower and is time consuming, tedious, and expensive. It also decreases the reactor's efficiency and adversely affects the profitability of the unit.
While various aeration diffusers have been used in sewage treatment plants, such as those shown in U.S. Pat. Nos. 3,220,706; 3,424,443; 3,608,834; and 3,954,922; such diffusers have not been used in reactors in oil refineries nor do they appear capable of mixing and distributing gases and oils, such as resid.
It is, therefore, desirable to provide an improved feed distributor and process which overcome most, if not all, of the preceding problems.
SUMMARY OF THE INVENTION
An improved feed distributor and process are provided to uniformly blend, mix, and distribute oil and gas feeds in a reactor of a hydroprocessing plant, such as an ebullated (expanded) bed reactor in an oil refinery or in a petrochemical plant. Advantageously, the novel feed distributor and process are efficient, effective, and economical.
The novel feed distributor and process improve conversion of resid and other types of oil, increase product quality, and enhance profitability of hydrotreating. Desirably, the novel feed distributor and process decrease the frequency of repair, reduce downtime, and enhance the useful life of refining equipment. The novel feed distributor and process minimize coke deposition and improve the flow patterns and oil and gas distribution in the hydrotreating reactors.
To this end, the feed distributor assembly has an annular conduit, tube, or manifold with an inlet and at least one outlet to feed the oil and hydrogen gases in a generally uniform flow pattern in the reactor. A hanger assembly or other connectors are provided to secure the feed distributor to the underside of the grid comprising the bubble tray and bubble caps.
In the preferred form, the feed distributor comprises an octagonal manifold with tapered outlet pipes providing tangential outlet openings, intermediate pipe sections providing a circumferential set of downwardly facing outlets, and a hood comprising a concentric set of vertical slotted skirts with radial discharge openings.
In order to use the feed distributor, an oil feed, preferably comprising resid, and a gas feed, preferably comprising hydrogen-rich gases, are intermixed and dispersed in a common feed line and fed to an annular manifold comprising the feed distributor. In the annular manifold, the oil and gas feeds are mixed to provide a substantially homogeneous mixture of oil and gases. The homogeneous mixture of oil and gases are discharged: (1) downwardly through the circumferential set of downwardly facing outlets in the intermediate pipe sections, (2) tangentially from the tangential outlet openings of the tapered outlet pipes, (3) radially inwardly from the inner slotted skirt of the hood, and (4) radially outwardly from the outer slotted skirt of the hood.
Desirably, the oil and gas feed is discharged in a uniform flow pattern to increase hydrotreating efficiency, effectiveness of the reactor, and resid conversion.
A more detailed explanation of the invention is provided in the following description and appended claims taken in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a cross-sectional view of an ebullated bed reactor containing a feed distributor assembly in accordance with principles of the present invention;
FIG. 2 is a perspective view of resid hydrotreating units and associated refinery equipment;
FIG. 3 is an enlarged perspective view of the feed distributor;
FIG. 4 is a top plan view of the feed distributor;
FIG. 5 is a fragmentary perspective front view of the inlet section of the feed distributor;
FIG. 6 is a fragmentary perspective bottom view of the inlet section of the feed distributor;
FIG. 7 is a fragmentary bottom view of intermediate sections of the feed distributor; and
FIG. 8 is a fragmentary bottom view of the outlet section of the feed distributor.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to FIG. 2, high-sulfur resid oil feed, also referred to as sour crude or vacuum-reduced crude, comprising 1,000+° F. resid and heavy gas oil, is fed into resid hydrotreating units 10, 12, and 14 along with a hydrogen-rich feed gas. Each resid hydrotreating unit is a reactor train comprising a cascaded series or set of three ebullated (expanded) bed reactors 16, 18, and 20. In the reactors, the resid is hydroprocessed (hydrotreated) in the presence of fresh and/or equilibrium hydrotreating catalyst and hydrogen to produce an upgraded effluent product stream leaving used spent catalyst. Hydroprocessing in the RHU includes demetalation, desulfurization, denitrogenation, resid conversion, oxygen removal (deoxygenation), and removal of Rams carbon.
As shown in FIG. 2, the resid hydrotreating units and associated refining equipment comprise three identical parallel trains of cascaded ebullated bed reactors 16, 18, and 20, as well as hydrogen heaters 22, influent oil heaters 24, an atmospheric tower 26, a vacuum tower 28, a vacuum tower oil heater 30, a hydrogen compression area 32, oil preheater exchangers 34, separators 36, recycled gas compressors 38, air coolers 40, raw oil surge drums 42, sponge oil flash drums 44, amine absorbers and recycled gas suction drums 46, and sponge oil absorbers and separators 48.
Each of the reactor trains comprises three ebullated bed reactors in series. The oil feed comprises resid oil (resid) and heavy gas oil. The gas feed comprises upgraded recycled gases and fresh makeup gases. Demetalation primarily occurs in the first ebullated bed reactor in each train. Desulfurization occurs throughout the ebullated bed reactors in each train. The effluent product stream typically comprises light hydrocarbon gases, hydrotreated naphtha, distillates, light and heavy gas oil, and unconverted hydrotreated resid. The hydrotreating catalyst typically comprises a hydrogenating component on a porous refractory, inorganic oxide support.
The resid hydrotreating unit is quite flexible and, if desired, the same catalyst can be fed to one or more of the reactors or a separate demetalation catalyst can be fed to the first reactor while a different catalyst can be fed to the second and/or third reactors. Alternatively, different catalysts can be fed to each of the reactors. The spent catalyst typically contains nickel, sulfur, vanadium, and carbon (coke). Many tons of catalyst are transported into, out of, and replaced in the ebullated bed reactors daily.
As shown in FIG. 1, fresh hydrotreating catalyst can be fed downwardly into the top of the first ebullated bed reactor 16 through a fresh catalyst feed line 49. Hot resid feed and hydrogen-containing feed gases enter the bottom of the first ebullated bed reactor 16 through a common feed line 50 and flow upwardly into an annular feed distributor 100. The feed distributor 100 comprises an octagonal manifold, torus, and header 104 which provide a plenum chamber positioned within the interior of the bottom portion of the ebullated bed reactor 16 to mix and blend the oil and gas feed in a homogeneous manner and to radially and annularly distribute the oil and gas feeds in a uniform flow pattern in the bottom portion of the reactor 16.
The uniform, homogeneous mixture of oil and gases flows upwardly through a grid 52 comprising a bubble tray or distributor plate 54 containing numerous bubble caps 58 and risers 60 which help further distribute the oil and gas across the reactor 16 and prevent catalyst from falling into the bottom section of the reactor. An ebullating pump 62 circulates oil from a recycle pan 64 through a downcomer 66 and the grid 52. The rate is sufficient to lift and expand the catalyst bed from its initial settled level to its steady state expanded level. The effluent product stream of partially hydrotreated oil and hydrogen-rich tail gases (off gases) is withdrawn from the reactor 16 through an effluent product line 68. The used spent catalyst is withdrawn from the bottom of the reactor through a spent catalyst discharge line 70. The spent catalyst typically contains deposits of metals, such as nickel and vanadium, which have been removed from the influent feed oil (resid) during hydrotreating.
Catalyst particles are suspended in a three-phase mixture of catalyst, oil, and hydrogen-rich feed gases in the reaction zone 72 of the reactor. Hydrogen-rich feed gases typically continually bubble through the oil. The random ebullating motion of the catalyst particles results in a turbulent mixture of the phases which promotes good contact mixing and minimizes temperature gradients.
The cascading of the ebullated bed reactors 16, 18, and 20 in a series of three per reactor train, in which the effluent of one reactor serves as the feed to the next reactor, greatly improves the catalytic performance of the back mixed ebullated bed process. Increasing the catalyst replacement rate increases the average catalyst activity.
As shown in FIG. 1, the feed distributor assembly 100 includes a bifurcated, generally Y-shaped feed header 102, a substantially octagonal, annular manifold comprising a feed distributor 104, and a hanger assembly 106. The hanger assembly 106 comprises a set of downwardly converging rods or bars 108 which extend between and connect the hanger flanges 110 or other portions of the feed distributor 104 to the underside of the grid 52 comprising the bubble tray 54. The rods 108 can be bolted, fastened, or otherwise securely connected to the feed distributor 104 and the grid 52. The hanger assembly 106 fixedly carries, cradles, hangs, supports, and positions the annular octagonal manifold (feed distributor) 104 about the downcomer 66 of the ebullated bed reactor 16.
As shown in FIG. 1, the feed header 102. has a generally V-shaped, common, combined inlet feed line 50. Common feed line 50 has an inlet end 112 to receive, combine, disperse, and mix an oil feed comprising resid and gas oil and a gas feed comprising hydrogen-rich gases. The common feed line 50 also has an outlet end 114 which is connected to and communicates with the bottom portion of the ebullated bed reactor 16 to feed the combined oil and gas feeds into the reactor. A curved vertex 116 connects the inlet end 112 and outlet end 114 of the common feed line 50.
An oil feed line 118 (FIG. 1) is positioned in alignment with, is connected to, and communicates with the inlet end 112 of the common feed line 50 to feed the oil feed into the common feed line 50. A gas feed line 120 has an elongated inlet portion 122 positioned parallel to the oil feed line 118 and has an outlet portion 124 positioned perpendicular to and offset from both the oil feed line 118 and the inlet end 112 of the common feed line 50. The outlet portion 124 of the gas feed line 120 is connected to and communicates with the inlet end 112 of the common feed line 50 to feed the hydrogen-rich gases into the common feed line. The gas feed line 120 has a substantially larger diameter than the oil feed line 118 in order to accommodate the desired material balance and flow rates.
As shown in FIG. 1, the octagonal manifold and feed distributor 104 provides a plenum chamber which is positioned within the interior of the bottom portion of the ebullated bed reactor 16. The manifold 104 is positioned above the ebullating pump 62 and below the grid 52 comprising the bubble tray 54, bubble caps 58, and risers 60. The octagonal manifold 104 annularly surrounds the downcomer 66 about the vertical axis of the ebullated bed reactor 16. The manifold provides an effective feed distributor for blending, mixing, and obtaining a homogeneous mixture of the feed oil and the hydrogen-rich feed gases. Desirably, the feed distributor 104 radially, annularly, circumferentially, tangentially, and vertically distributes the oil and gas feed in the bottom portion of the reactor 16 in a substantially uniform flow pattern.
As shown in FIGS. 3 and 4, the octagonal manifold and feed distributor 104 has eight manifold sections with opposite ends including an inlet manifold section 126, an outlet manifold section 128, and six intermediate manifold sections 130, 132, 134, 136, 138, and 140. The opposite end portions 142 and 144 of each of the manifold sections 126-140 have an inverted U-shaped mounting flange 146 with bolt holes 148 to abuttingly engage a similar U-shaped mounting flange of an adjacent manifold section. Each of the opposite end portions 142 and 144 of the manifold sections 126-140 can also have an upwardly extending hanger flange 110 with a bolt hole or rod receiving opening 150. Fasteners 149 (FIG. 5), such as bolts 151 and nuts 152, securely connect and mount the engaged U-shaped flanges 146 together. As shown in FIG. 4, the outlet section 128 and the intermediate sections 130-140 are V-shaped with an included obtuse angle of about 140° as viewed from the top of the octagonal manifold 104.
As best shown in FIGS. 5 and 6, the inlet section 126 of the octagonal manifold and the feed distributor 104 has an enlarged inlet head 154 with a planar or flat circular disk 156 providing a top and an annular, circular sidewall 158 extending vertically downwardly from the disk 156 to provide an inlet opening and mouth 160. A lower annular circular flange 162 with bolt holes 164 annularly and circumferentially surrounds the inlet opening 160 and is connected to and diametrically extends outwardly of the bottom portion of the annular sidewall 158. The annular sidewall 158 has diametrically opposite inlet ports 166 and 168.
The inlet manifold section 126 (FIGS. 5 and 6) has substantially diametrically opposite, inlet pipe sections 170 and 172 which communicate with the inlet ports 166 and 168 and are connected to and extend radially outwardly from the annular sidewall 158 of the inlet head 154. The inlet manifold section 126 also has diametrically opposite inlet skirt portions 174 and 176 which are welded or otherwise securely connected to and cantilevered from the diametrically opposite inlet pipe sections 170 and 172, respectively. Each of the inlet skirt portions 174 and 176 has a pair of parallel vertical inlet flanges 178 and 180 or 182 and 184 which are welded or otherwise tangentially connected to and extend vertically downwardly from the inlet pipe sections 170 and 172. Each of the inlet skirt portions 174 and 176 also has a transverse flange 186 or 188 which extends transversely and perpendicularly between and is welded or otherwise connected to the inlet skirt flanges 178 and 180 or 182 and 184. The transverse skirt flanges 186 and 188 have a rounded concave upper end portion 190 and 192 which are welded or otherwise arcuately connected to and extend vertically downwardly from the inlet pipe sections 170 and 172 at a location spaced radially outwardly of the annular sidewall 158 of the inlet head 154. Each of the inlet skirt flanges 178-184 has an outer end 194 or 196 which is welded or otherwise connected to one of the U-shaped mounting flanges 146. Each of the skirt flanges 178-184 also has a lower inlet portion 198 or 200 with an inlet set of elongated, vertical inlet discharge slots 202, 204, 206, or 208.
As shown in FIG. 1, the inlet manifold section 126 has a downwardly extending elbow pipe or tube 210 with an upper, circular, annular flange 212 which is mounted against and connected to the lower annular flange 162 of the inlet head 154. The elbow pipe 210 has a lower inlet portion 214 which is snugly connected to and communicates with the outlet end portion 114 of the common feed line 50.
The outlet manifold section 128 (FIG. 4) is positioned diametrically opposite the inlet manifold section 126. As best shown in FIG. 8, the outlet section 128 of the octagonal manifold and feed distributor 104 has a pair of outlet pipe sections 216 and 218. Each of the outlet pipe sections 216 and 218 has an enlarged influent portion 220 or 222, which has the same diameter as the other pipe sections, and has a tapered outlet portion 224 or 226 which provides a constricted outlet opening and mouth 228 and 230. The outlet openings 228 and 230 have a much smaller diameter than the influent portions 220 and 222 of the outlet pipe sections 216 and 218. The outlet openings 228 and 230 generally face and are spaced apart from each other. The outlet openings 228 and 230 tangentially discharge some of the oil and gas feed. The outlet pipe sections 216 and 218 are positioned at an angle of inclination of about 45° from each other and are spaced apart from each other. In one test unit, the area of the eccentric reducers (tapered outlet pipe sections) was about 18 percent of the inlet nozzle area (enlarged influent portions).
The outlet manifold section 128 (FIGS. 3 and 8) has an inverted U-shaped skirt 236 comprising a pair of vertical outlet skirt portions 236 and 240. The outlet skirt portions are welded or otherwise securely connected to and intersect each other at an angle of inclination of about 45°. Each of the outlet skirt portions has an inverted U-shaped, upper bight 242 or 244 which provides a top portion that is positioned above and protectively covers the outlet pipe sections 216 and 218. Each of the outlet skirt portions has a pair of parallel, vertical outlet skirt flanges 246 and 248 or 250 and 252 which are welded or otherwise securely connected to and cantilevered downwardly from the U-shaped bight. Each of the outlet skirt flanges has an outer end 254, 256, 258 or 260 (FIG. 4) which is welded or otherwise securely connected to one of the U-shaped mounting flanges 146. Each of the outlet skirt flanges also has a lower outlet portion 262, 264, 266, or 268 which provides an outlet set of elongated, vertical discharge outlet slots 270, 272, 274, and 276.
Each of the intermediate manifold sections 130-140 (FIGS. 3, 4, and 7) has a pair of intermediate pipe sections 278 and 280. The intermediate pipe sections 278 and 280 are connected to and communicate with each other and with an adjacent pipe section. The intermediate pipe sections 278 and 280 are positioned at an angle of inclination of about 45° to each other and to an adjacent pipe section. Each of the intermediate pipe sections 278 and 280 has a downwardly facing, elongated, oblong opening or slot 282 or 284 which provides discharge outlets to discharge most of the oil and gas feeds downwardly. In one test unit, the total area of the downwardly facing slots in the pipe sections was about 59 percent of the inlet nozzle area so that the velocities were sufficient for substantially equal distribution around the feed distributor.
Each of the intermediate manifold sections 130-140 (FIGS. 3, 4, and 7) also has a pair of intermediate skirt portions 286 and 288. The skirt portions 286 and 288 are welded or otherwise connected to each other. The intermediate skirt portions 286 and 288 are connected to adjacent skirt portions via the U-shaped mounting flanges 146. The intermediate skirt portions 286 and 288 are also positioned at an angle of inclination of about 45° to each other and to an adjacent skirt portion. Each intermediate skirt portion 286 and 288 includes a pair of parallel, vertical, intermediate skirt flanges 290 and 292 or 294 and 296. The intermediate skirt flanges are welded or otherwise tangentially connected to and extend and are cantilevered downwardly from the intermediate pipe sections 278 and 280. Each of the intermediate skirt flanges has an outer end 298 welded or otherwise connected to one of the U-shaped mounting flanges 146. Each of the intermediate skirt flanges also has a lower portion 300, 302, 304, or 306 with an intermediate set of elongated, vertical, intermediate discharge slots 308, 310, 312, or 314.
The skirt portions of the inlet, outlet, and intermediate sections 126-130 of the octagonal manifold and feed distributor 104 cooperate with each other and the pipe sections of the octagonal manifold and feed distributor 104 to provide an octagonal skirt and hood 316 (FIG. 3). The octagonal skirt and hood 316 extends eccentrically about the inlet head 154. In one test unit, the hood extended circumferentially about 335° around the inside of the ebullated bed reactor at about two-thirds of the reactor's internal diameter so that the area radially inwardly of the feed distributor was about equal to the area radially outwardly of the feed distributor.
The vertical, upright discharge slots of the skirt portions of the octagonal skirt and hood 316 (FIG. 3) cooperate with each other to provide concentric inner and outer octagonal sets 318 and 320 of radial slots. The slots provide for overflow, spillage, and radial discharge of the oil and gas feeds. The inner set of inner radial slots 320 discharges some of the oil and gas feeds radially inwardly. The outer set of outer radial slots 318 discharges some of the oil and gas feeds radially outwardly.
As shown in FIGS. 6-8, a set of transverse reinforcing bars or rods 322 is welded or otherwise securely connected to, extends radially between, and is positioned perpendicular to the skirt portions of the outlet manifold section 128 and the intermediate manifold sections 130-140. The reinforcing bars 322 are spaced below the outlet pipe sections and the intermediate pipe sections, respectively. The reinforcing rods help reinforce and rigidify the octagonal skirt and hood.
In operation, an oil feed comprising resid and gas oil is fed downwardly through the oil feed line 118 (FIG. 1) into the inlet end 112 of the common feed line 50. Simultaneously, a gas feed comprising hydrogen-rich gases is injected downwardly through the gas feed line 120 into the inlet end 112 of the common feed line 50. The oil and gas feeds are dispersed and mixed in the common feed line 50 and are passed upwardly through the outlet end 114 into the inlet manifold section 126 of the octagonal manifold and feed distributor 104.
In the octagonal manifold and feed distributor 104 (FIG. 4), the oil and gas feeds are separated into two streams: (1) a clockwise stream of oil and gas which passes through the left inlet pipe section 170, the left intermediate pipe sections 130-134, and the left outer pipe section 216; and (2) a counter-clockwise stream of oil and gas which passes through rhe right inlet pipe section 172, the right intermediate pipe sections 136-140, and the right outlet pipe section 218. The clockwise and counter-clockwise streams provide an arcuate, annular, or octagonal flow distribution whicn mixes and blends the oil and gas feeds into a substantially homogeneous mixture for more effective hydrotreating. The oil and gas feeds are discharged downwardly through the downwardly facing discharge openings 282 and 284 and tangentially clockwise and counter-clockwise through the tangential outlet openings 228 and 230. The tangential outlet openings provide an auxiliary outlet in the event of coking or plugging of the downwardly facing discharge openings. The tangential openings also enhance self-cleaning of the distributor to minimize coking or plugging of the downwardly facing discharge openings. The oil and gas feed spills outwardly from the bottom open end of the octagonal skirt and hood 316 and flows radially inwardly and outwardly through the inner and outer slots of the octagonal skirt and hood 316. The oil and gas feed is distributed and discharged in a substantially uniform flow pattern.
The oil and gas feeds which have been discharged from the octagonal manifold and feed distributor 104 (FIG. 1) are passed upwardly through the risers 60 and bubble caps 58 before entering the reaction zone of the reactor 16. Fresh hydrotreating catalyst can be fed downwardly through the catalyst feed line into the reaction zone of the reactor 16.
In the reaction zone of the reactor 16 (FIG. 1), the oil and gas feeds are ebullated and hydroprocessed in the presence of the fresh hydrotreating catalyst to produce an effluent product stream of upgraded hydrotreated oil and reactor tail gases (off gases) which is withdrawn from the ebullated bed reactor 16 through an effluent product line. The used spent catalyst is withdrawn from the bottom of the ebullated bed reactor 16 through the spent catalyst discharge line.
The novel feed distributor assembly and process has been extensively tested at the Amoco Oil Company Refinery in Texas City, Tex. and has been found to produce unexpected, surprisingly good results.
Among the many advantages of the novel feed distributor assembly and process are:
1. Superior mixing, blending, dispersion, and distribution of oil and gas feeds.
2. Increased conversion of resid to more valuable products.
3. Excellent process efficiency.
4. Improved process effectiveness.
5. Establishes a more stable, uniform gas-liquid interface level under the grid.
6. Better product quality.
7. Enhanced operability.
8. Lower operating and maintenance costs.
9. Reduced downtime.
10. Ability to distribute a three-phase feed.
11. Capability of handling solid-laden fluids.
12. Self-cleaning.
13. Prevent coking above, on, and under the grid.
14. Minimized catalyst agglomeration on the grid.
15. Can be retrofitted to existing reactors.
16. Readily removeable for maintenance.
Although embodiments of this invention have been shown and described, it is to be understood that various modifications and substitutions, as well as rearrangements and combinations of process steps and equipment, can be made by those skilled in the art without departing from the novel spirit and scope of this invention. | A special feed distributor is provided to radially, annularly, and uniformly feed and distribute oil and gas in a hydroprocessing unit, such as an ebullated bed reactor. In the preferred form, the feed distributor comprises an octagonal manifold with tangential outlet openings, a circumferential set of downward outlets, and a slotted skirt with radial discharge openings. | 1 |
BACKGROUND
[0001] The present disclosure relates to counterbalance mechanisms and in particular to a device for safely absorbing energy from a part of a counterbalance mechanism accidentally released by a failure of a part of such a counterbalance mechanism.
[0002] Counterbalance mechanisms have long been used to make it possible to raise heavy objects by providing a force in opposition to the weight of such a heavy object. The force provided by the counterbalance mechanism typically is slightly less than a load that is desired to be balanced so that the counterbalance mechanism supports a large part of the load in a static condition. Such an arrangement allows for the load to be easily moved by applying a small additional force, in comparison to the force that would otherwise be required to move the load without the counterbalance mechanism.
[0003] Counterbalance mechanisms have been used extensively in many mechanical devices, including lift bridges and the like. One such application is in a railroad freight car which has multiple decks that are capable of carrying cargo. U.S. Pat. Nos. 5,743,192, 5,794,537, and 5,979,335 disclose a multi-unit railroad freight car for carrying automobiles on multiple levels of decks. In each of the disclosed freight cars, a plurality of automobiles may be supported on decks that are adjustable in height. Each end portion of the middle level deck in each unit of the freight cars is mounted on a pivot axis at its inner end so that the outer end portion of the deck, located at the end of the car unit, may be raised and lowered to facilitate the loading and unloading of vehicles on the lowest level of the car.
[0004] In U.S. Pat. No. 7,055,441, the specification of which is incorporated herein by reference, a counterbalance mechanism allows a pivoted end portion of the middle level deck of such a railroad freight car to be raised and lowered easily by its operator. The counterbalance mechanism has an elongate tension-carrying member, coupled to the hinged end portion of the deck, that applies a lifting force from a spring to allow a person to raise the hinged end portion of the deck with mere hand pressure. The lifting force provided by the counterbalance mechanism assists the operator in raising the hinged end portion of the deck by carrying much of its weight as it is moved between its raised and lowered positions.
[0005] Such a counterbalance mechanism entails the risk that failure of a tension-carrying cable might free a powerful spring or a large counter-weight, causing damage to the counterbalance mechanism and potentially causing injury to an operator. In the event of a failure of the tension-bearing member, the counterbalance mechanism may release an amount of energy related to the force that was supporting the counterbalanced object, and a part of the counterbalance mechanism may be released to potentially cause structural damage and personal injury. The counterbalance mechanism for decks within a railroad freight car may be supporting more than a ton of weight, and the energy released if a failure occurs is potentially great.
[0006] The energy that is potentially freed as a result of a failure in the counterbalance mechanism, thus presents a risk of damage to the remainder of a counterbalance mechanism and the associated structure of the freight car, and a risk of injury to nearby personnel.
[0007] What is needed, then, is an energy-absorbing mechanism capable of absorbing a large portion of the energy that may be released in the event that a failure occurs in a counterbalance mechanism in a railroad freight car, so that the failure of the counterbalance mechanism will not result in structural damage to the railroad car or injury to nearby personnel.
SUMMARY OF THE DISCLOSURE
[0008] The mechanism disclosed herein answers the aforementioned needs by providing an energy-absorbing device as defined by the appended claims. In one embodiment such a device may be associated with a counterbalance mechanism, to protect a railroad car and nearby personnel from injury in case of a failure of the counterbalance mechanism.
[0009] In one embodiment the device disclosed includes a deformable support member that gives way in response to an impact resulting from a failure of a load supporting portion of a counterbalance mechanism. The energy-absorbing device is attached to a housing for a force-generating element of the counterbalance mechanism, such as a spring or a counterweight, and prevents a suddenly released force-generating element and force-transmitting member from damaging the structure of the freight car, by cushioning an impact and absorbing a large portion of the energy of the force-generating element.
[0010] One embodiment of the energy-absorbing device is associated with a counterbalance mechanism that supports a movable hinged end portion of a deck of a railroad freight car.
[0011] In one embodiment of the disclosed apparatus, the energy-absorbing device includes a blocking or impact receiving member mounted on a plurality of deformable support members. The impact receiving member is connected with a frame attached to an end of a housing for a movable part of the counterbalance mechanism. In the event of a failure, a released part of the counterbalance mechanism that moves toward the blocking or impact receiving member strikes the member on a face that is directed toward the interior of the housing. As a result of such an impact, the deformable support members are bent from their original configurations and thereby absorb the kinetic energy of the released part.
[0012] In one embodiment, the energy-absorbing device is attached to a housing for a moving portion of a counterbalance mechanism and includes attachment bars extending away from an end of the housing. The deformable support members may be of a “U” shape and may be located where they are urged to bend in response to collision of released parts of a counterbalance mechanism against an impact receiving member so that they absorb the energy from moving parts released by failure of a part of the counterbalance mechanism.
[0013] In one embodiment one end of each U-shaped deformable support member is attached to a side of the impact receiving member opposite a face which the moving force-generating element of the counterbalance mechanism would strike if set free as by a failed cable. The other end of each of the U-shaped deformable support members may be connected to the attachment bars by a detachable fastener such as a nut and bolt combination. This structure allows the deformed portion of energy-absorbing device to be replaced after an impact occurs, by simply detaching the deformable support members from the attachment bars.
[0014] In one embodiment of the energy-absorbing device the blocking or impact receiving member may be a plate in the shape of an annular ring defining a central opening through which a fitting attached to an end of the counterbalance mechanism may fit.
[0015] In one embodiment of the energy-absorbing device, the attachment bars are beveled to provide additional space into which the deformable support members may be deformed in order to absorb additional energy from a moving member of a counterbalance mechanism.
[0016] The foregoing and other objectives, features, and advantages of the invention will be more readily understood upon consideration of the following detailed description of the invention, taken in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
[0017] FIG. 1 is a cutaway side elevational view of a portion of one unit of a multi-unit railroad freight car, showing a movable end portion of an automobile-carrying deck located in an upwardly inclined position.
[0018] FIG. 2 is an interior detail view, at an enlarged scale, showing the uppermost portion of one side wall of the body of the unit of a railroad freight car shown in FIG. 1 , showing an end of a deck in a raised position, and also showing a counterbalance mechanism equipped with an energy-absorbing mechanism.
[0019] FIG. 3 is an isometric bottom view, at an enlarged scale, of the energy-absorbing mechanism shown in FIG. 2 , also showing the bottom portion of a guide tube portion of the counterbalance mechanism.
[0020] FIG. 4 is an exploded isometric bottom view of the energy-absorbing mechanism shown in FIG. 3 .
[0021] FIG. 5 is a sectional view, taken along line 5 - 5 of FIG. 3 , showing a portion of the counterbalance apparatus in a lightly loaded condition within the guide tube.
[0022] FIG. 6 is a sectional view, taken along line 5 - 5 of FIG. 3 , showing a portion of the counterbalance apparatus after having struck the energy-absorbing device and also showing the deformable support members in a deformed state.
[0023] FIG. 7A is a sectional view of the combination of one of the deformable support members and an alternative embodiment of an attachment bar.
[0024] FIG. 7B is a sectional view of the support member and attachment bar shown in FIG. 7A , showing the deformable support member in a deformed condition.
DETAILED DESCRIPTION OF EMBODIMENTS
[0025] Referring to the drawings which form a part of the disclosure herein, FIG. 1 shows part of a car body 10 of one car unit of a multi-unit railroad freight car that incorporates an energy absorber for a counterbalance mechanism. The freight car may include two or more adjacent car units, and each respective car unit may include a cargo well 12 , a middle deck 14 , and an upper deck 16 , for selectively supporting and storing automobiles 18 in a tri-level arrangement. Each deck preferably has a shape that provides ample strength for supporting automobiles 18 , while providing sufficient space to accommodate automobiles 18 of various heights that the car is desired to carry.
[0026] As can be seen in FIG. 1 , the automobiles 18 stored on the lowest level of the freight car body 10 rest in the respective cargo well 12 of each car unit. In order to maximize use of the available vertical space in the upper two cargo levels, the middle deck 14 is positioned where it would prevent the loading and unloading of automobiles 18 from the cargo well 12 were it not for a hinged end portion 20 of the middle deck 14 that may be selectively raised while automobiles 18 are loaded into or unloaded from the cargo well 12 . It is to be understood that each of the car units may have a middle deck 14 and an upper deck 16 , and that the middle deck 14 in each car unit may include a hinged end portion 20 at either or each end.
[0027] A respective counterbalance apparatus 22 is provided at each side of the car unit to carry part of the weight of the hinged end portion 20 so that it may be raised easily when necessary. The counterbalance apparatus includes an energy-absorbing device 24 in order to absorb energy that may be released should a failure of the counterbalance apparatus 22 occur and result a part of the counterbalance apparatus 22 being freed to move. The energy-absorbing device 24 prevents an impact of such a freed part of the counterbalance apparatus from causing substantial damage to the counterbalance apparatus 22 to an associated housing, or to the associated supporting structure of the freight car body 10 . Furthermore, a portion of the energy-absorbing device 24 may be replaced after an impact and thus can reduce costs for repairs if a failure of the counterbalance apparatus 22 occurs.
[0028] Each counterbalance apparatus 22 may include a force-transmitting member, such as a cable 28 or chain (not shown) that interconnects and transmits forces between a counterbalanced object such as the hinged end portion 20 and a force-generating element, such as a spring 32 or a counterweight (not shown). The force-generating elements of the counterbalance mechanisms 22 together may generate a lifting force that is slightly less than the applied portion of the weight of the hinged end portion 20 . Each force-transmitting member may include a first elongate tension carrying segment 34 operatively connected to, and extending upward from, the hinged end portion 20 and a second elongate tension carrying segment 36 operatively interconnected with the force-generating element so that tension in the first elongate tension carrying segment 34 is caused by tension in the second elongate tension carrying segment 36 , which in turn is caused by the force-generating element.
[0029] In a simple counterbalance mechanism, the force-transmitting member may be a cable 28 , and the force-generating element may include the spring 32 . In that instance, it may be appropriate to include a direction changing force transfer device 42 , including one or more sheaves 44 , or other mechanisms such as bell cranks (not shown). The direction changing force transfer devices 42 may be positioned between the first elongate tension carrying segment 34 and the second elongate tension carrying segment 36 . In a more complex counterbalance mechanism, an appropriate force-transmitting arrangement might include gears, rigid members, bell cranks, etc.
[0030] The middle deck 14 may be provided in the form of three segments arranged end-to-end, with the center segment fastened securely and tightly to the side posts 40 by bolts or other releasable but secure fasteners so that the middle deck 14 is incorporated structurally in, and adds rigidity to, the entire car unit as well as being solidly supported by the side walls 46 .
[0031] Hinges 47 pivotally attach the hinged end portion 20 to two horizontal support beams 48 that extend longitudinally along the opposite side walls 46 of the car body 10 at equal heights and that are rigidly fastened to the side walls 46 by fasteners such as bolts. Each of the horizontal support beams 48 extends inwardly from the side walls 46 , so that when the hinged end portion 20 is in a lowered position it is supported along its lateral margins by the horizontal support beams 48 . In this manner, the horizontal support beams 48 support the portion of the weight of the hinged end portion 20 and any automobiles 18 or other cargo carried on the hinged end portion 20 in excess of the weight supported by the counterbalance apparatus 22 . Each of the horizontal support beams 48 is positioned at a vertical height along its respective side wall 46 where the hinged end portion 20 abuts the fixed portion of the middle deck 14 at a pivot axis defined by the hinges 47 through which the inner end of the hinged end portion 20 is attached. The hinges may allow an outer end 50 of the hinged end portion 20 of the middle deck 14 to be raised as much as about 4 feet to an inclined position above the horizontal support beams 48 . Raising the hinged end portion 20 of the middle deck 14 while it is empty allows automobiles 18 to be moved over the trucks 52 and the body bolsters 54 of the car body 10 and into or out of the cargo well 12 during loading and unloading of the freight car 2 .
[0032] Referring to FIG. 2 , the counterbalance apparatus 22 is used to support most of the weight of the hinged end portion 20 so that it may easily be raised and lowered manually. The counterbalance apparatus 22 applies a lifting force from the force-generating element to the outer end 50 of the hinged end portion 20 through a tension-carrying member, which may be, for example, a flexible 5/16″ diameter steel cable 28 . The cable 28 operatively connects the hinged end portion 20 to the force-generating element and extends upward and around sheaves 44 which may be mounted in fixed locations, such as between the corner post 38 and the side post 40 that is next to the corner post 38 along the side wall 46 in the direction toward the mid-length of the car body 10 .
[0033] Referring again to FIG. 2 , the generally helical compression spring 32 or another force-generating element may be held in a protective housing such as a guide tube 56 , securely mounted in the car body 10 , where the compression spring 32 is free to extend and be compressed, or a counterweight is free to move up or down. The compression spring 32 and the guide tube 56 may also be located in an interior space that lies between the corner post 38 and the adjacent side post 40 . In this way, the counterbalance apparatus 22 is situated in what is otherwise unused space inside the railroad car body 10 and does not interfere with any other structure or cargo inside the car.
[0034] The guide tube 56 comprises an interior liner sleeve 58 (shown in FIGS. 5-6 ), and an upper end fitting 60 that is securely connected to the guide tube 56 , retains the upper end of the spring 32 and opposes the force of the cable 28 in order to compress the spring 32 and thus provides a force supporting part of the weight of the movable deck part 20 . The sleeve 58 may be made from, or at least lined with, a layer of polymeric resin such as UHMW polyethylene so that friction and wear may be minimized as the compression spring 32 moves within the guide tube 56 .
[0035] The upper fitting 60 defines an opening 62 . The cable 28 extends through the opening 62 and through the compression spring 32 , and is secured to a cable end fitting 64 , as by being looped around a crosspin of the end fitting 64 and held by a swaged or cast cable fastener 66 , shown in FIGS. 5-6 .
[0036] Referring to FIGS. 5-6 , the cable end fitting 64 is connected to the end of the spring 32 as by mating with a suitable spring retainer 68 . The spring retainer 68 may, as shown, be in the form of a cup with a suitably sturdy annular bottom plate 70 and an upwardly extending sidewall 72 that surrounds a bottom end of the spring 32 , so that the retainer 68 acts as a piston supporting the lower end of the spring 32 and guides the spring 32 as it moves within the guide tube 56 . The end fitting 64 may have an upwardly projecting part that fits matingly through the central opening 74 in the bottom plate 70 and a radial flange 76 , extending beneath the bottom plate 70 , that is too large to pass through the opening 74 . The sleeve 58 facilitates movement of the retainer 68 within the guide tube 56 . Because of the arrangement of the cable 28 , movement of the hinged end portion 20 up or down causes the retainer 68 to slide oppositely within the sleeve 56 . Movement of the retainer 68 , in turn, compresses the compression spring 32 or allows it to expand downward beneath the upper fitting 60 , depending on the direction in which the retainer 68 is moving.
[0037] The length of the cable 28 and the force of the compressed spring 32 may be such that when the hinged end portion 20 is in the lowered position the compression spring 32 applies a lifting force to the hinged end portion 20 that is slightly less than that which would lift the outer end 50 of the hinged end portion 20 . It will be understood that the compression spring 32 should be long relative to the distance through which given a point on the cable 28 will travel when the hinged end portion 20 of the middle deck 14 is raised or lowered, so that the magnitude of the lifting force supplied by the counterbalance apparatus 22 remains within a small range during raising and lowering of the hinged end portion 20 . The hinged end portion 20 of the middle deck 14 can thus be raised easily during loading of automobiles 18 into the cargo well 12 to provide ample overhead clearance above the body bolster 54 as automobiles pass over the wheeled truck 52 at each end of the multi-unit freight car or over a shared truck between car units.
[0038] FIGS. 2-6 show the energy-absorbing device 24 that is used to absorb the energy from a spring 32 or other force-generating element released by a failure in the counterbalance apparatus 22 such as a failure of the cable 28 . Such a released spring 32 would result in an impact of the retainer 68 against the energy-absorbing device 24 . If the cable 28 should fail, the spring 32 would rapidly expand from a compressed condition between the upper fitting 60 and the retainer 68 , launching itself, the spring retainer 68 , the end fitting 64 , and any attached portion of the cable 28 downward through the guide tube 56 toward the energy-absorbing device 24 . The energy-absorbing device 24 helps to prevent substantial damage from occurring to the guide tube 56 and helps to prevent injury from occurring to an operator who may be manually lifting the hinged end portion 20 of the middle deck 14 . The energy-absorbing device 24 may be constructed as shown, to include energy-absorbing parts that are easily replaced after an impact occurs. The construction of the energy-absorbing device 24 also allows for ready access to the interior of the guide tube 56 so that repairs may be made to the spring 32 or cable 28 .
[0039] Referring now to FIGS. 3 and 4 , as depicted, the energy-absorbing device 24 is attached to the lower end of the guide tube 56 and includes a base that may be in the form of a collar 82 , which may be welded to the guide tube 56 , and a plurality of attachment bars 84 , each securely attached as by being welded to or formed as an integral part of the collar 82 . In one embodiment, the collar 82 is welded or otherwise fixedly attached to the guide tube 56 ; however, it will be understood that the collar 82 may be detachable so long as it is capable of withstanding the maximum anticipated amount of energy from a potential impact of a released part of a counterbalance mechanism without separating from the guide tube 56 .
[0040] A first, or outer, end of a deformable support member 86 is detachably connected to each attachment bar 84 as by a fastener such as a bolt and nut combination 88 . Each deformable support member 86 is a metal strap bent into a “U” shape, with the second end 90 of the strap, which may be wider than the first or outer end, being attached to an impact receiving, or blocking member 92 that fits within or is aligned with the lower end of the guide tube 56 to block, or close, that end of the guide tube 56 and thus safely contain the spring 32 , the spring retainer 68 , and the end fitting 64 in the case of a cable failure.
[0041] The impact receiving member 92 and the guide tube 56 are similarly shaped, and the impact receiving member 92 has a slightly smaller size than the interior of the guide tube 56 , so that it fits within the guide tube 56 . For example, the guide tube 56 and impact receiving member 92 may be of a cylindrical shape, in which case the diameter 93 of the impact receiving member 92 is slightly smaller than the internal diameter of the guide tube 56 , and the impact receiving member 92 may fit within the interior of the guide tube 56 , loosely enough not to jam in the collar 82 when struck by a released part of the counterbalance mechanism, as shown in FIGS. 5 and 6 .
[0042] The impact receiving member 92 may be of flat plate steel in the form of an annular ring that defines a central hole 94 , as shown in FIG. 4 . The impact receiving member 92 has an upper, or first face 96 and a lower, second face 98 . The radial distance between the central hole 94 and the exterior margin is designed to provide room for attachment of the upper end 90 of each deformable support member 86 . The upper ends 90 of the deformable support members 86 may be attached as by being welded, to the second face 98 in uniformly spaced-apart positions about the central hole 94 . A pair of mounting ears 100 are attached to the second face 98 of the impact receiving member 92 , aligned with each other on opposite sides of the central hole 94 along an imaginary diametric line across the annular plate 92 , as shown in FIGS. 3 and 4 . Each mounting ear 100 is located between two deformable support members 86 in one embodiment.
[0043] A stopper bar 102 is attached to the ears 100 , extending along the diameter of the impact receiving member 92 and between the ears 100 , attached, for example, by bolt and nut combination 101 . The stopper bar 102 thus extends across the hole 94 as shown in FIG. 3 , at a location spaced a small distance beneath the lower face 98 , leaving room for the cable end fitting 64 to protrude through the central hole 94 when the bottom plate 70 of the retainer 68 contacts the annular impact receiving plate member 92 . The length of the stopper bar 102 is slightly less than the diameter of the interior of the guide tube 56 so that the stopper bar 102 fits within the guide tube 56 , as shown in FIG. 3 .
[0044] The deformable support members 86 may be of any configuration that is capable of bending in response to an impact against the impact receiving plate 92 and thus absorbing energy from the moving spring 32 or a counterweight from a counterbalance mechanism. As shown in FIGS. 3 and 4 , the deformable support members 86 may be of steel plate cut to a slender flat bar shape and bent to be generally “U” shaped, so that each deformable support member 86 includes an attached or upper end 90 , a U-shaped central portion 104 , and the detachable end 106 . The U-shaped central portion 104 of the deformable support member 86 extends away from the second or lower face 98 of the annular blocking member 92 . The detachable end 106 of the deformable support member 86 extends parallel with the attached end 90 generally toward the second face 98 of the impact receiving element 92 at a location radially further outward from the central hole in the annular impact receiving member 92 , but it does not extend the entire distance back to the second face 98 . The detachable end 106 of the deformable support member 86 defines a hole 108 that is aligned with a hole 110 defined in the lower portion of the attachment bar 84 when the annular impact receiving member 92 is fitted within the collar 82 . The nut and bolt combinations 88 thus detachably attach the disposable and replaceable part of the energy-absorbing assembly 24 to the collar 82 .
[0045] FIGS. 3 and 4 show that four deformable support members 86 are used, although it will be understood that any convenient number of deformable support members 86 suitable to absorb the anticipated amount of energy from the counterbalance mechanism may be used with an equal number of attachment bars 84 . The embodiment shown in FIGS. 3 and 4 has deformable support members 86 evenly spaced apart around the interior perimeter 100 of the annular ring 96 so that each deformable support member 86 is located to absorb a substantially equal amount of energy if an impact occurs.
[0046] Referring again to FIGS. 5 and 6 , the energy-absorbing device 24 is attached to one end of the guide tube 56 as by welding the collar 82 to the guide tube 56 adjacent its lower end, where the energy absorbing device can block a released portion such as the spring 32 and cable 28 of a counterbalance mechanism, and receive the impact of a released part in the event that a failure occurs in the counterbalance apparatus 22 . The force-generating element fits within the spring retainer 68 and drives the retainer 68 through the guide tube 56 . The end fitting 64 may be smaller than the central opening 94 in the annular impact receiving plate member 92 and fits through the central opening 94 if the spring 32 is released by failure of the cable 28 and drives the retainer 68 against the annular impact receiving member 92 . The end fitting 64 can then strike and perhaps be contained by the stopper bar 102 .
[0047] Referring to FIG. 6 , in the event of a failure, the retainer 68 , driven by the spring 32 , impacts the annular impact receiving plate element 92 and the end fitting 64 passes through the central hole 94 defined in the annular impact receiving plate member 92 . In response to the impact, the deformable support members 86 flex and are plastically deformed to absorb much of the energy transferred from the spring 32 by the impact. The material of which the deformable support members are made is malleable enough to absorb the maximum energy caused by such an impact by bending, rolling the “U” bend along the straplike deformable members 86 , rather than fracturing. Any parts, such as the end fitting 64 , that pass through the central opening 94 in the impact receiving member 92 will contact the stopper bar 102 and thus be kept from simply passing freely out from the guide tube 56 .
[0048] Referring now to FIGS. 7A and 7B , the interior surface 114 of the lower portion of each attachment bar 84 may be beveled. The beveled end 114 creates additional space into which for the deformable support members 86 can deform in the event an impact occurs, as shown in FIG. 7B . In a pre-impact condition, as shown in FIG. 7A , a portion of the detachable end 106 of the deformable support member 86 is not in contact with the beveled end 114 . When an impact occurs, the deformable support member 86 may flex to deform a greater distance in a radial direction as compared to a deformable member 86 supported by an attachment bar 84 with a non-beveled end.
[0049] The terms and expressions which have been employed in the foregoing specification are used therein as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding equivalents of the features shown and described or portions thereof, it being recognized that the scope of the invention is defined and limited only by the claims which follow. | An energy-absorbing device for use with a counterbalance mechanism to relatively harmlessly absorb energy potentially released should a component of the counterbalance mechanism fail. A frame is attached to a portion of the counterbalance mechanism and supports an impact receiving member, and a plurality of deformable support members. In the event of a failure in the counterbalance mechanism, a part of the counterbalance mechanism strikes a face of the impact receiving member. Deformable support members are attached to the opposing face of the impact receiving member and are deformed by the impact and thus absorb the energy that is transferred by the impact. The deformable support members and the impact receiving member are readily replaceable. | 1 |
FIELD OF THE INVENTION
[0001] The present invention relates to 4-aryl-6-piperazin-1-yl-3-substituted-pyridazines that are fast dissociating dopamine 2 receptor antagonists, processes for preparing these compounds, pharmaceutical compositions comprising these compounds as an active ingredient. The compounds find utility as medicines for treating or preventing central nervous system disorders, for example schizophrenia, by exerting an antipsychotic effect without motor side effects.
DESCRIPTION OF THE INVENTION
[0002] Schizophrenia is a severe and chronic mental illness that affects approximately 1% of the population. Clinical symptoms are apparent relatively early in life, generally emerging during adolescence or early adulthood. The symptoms of schizophrenia are usually divided into those described as positive, including hallucinations, delusions and disorganised thoughts and those referred to as negative, which include social withdrawal, diminished affect, poverty of speech and the inability to experience pleasure. In addition, schizophrenic patients are suffering from cognitive deficits, such as impaired attention and memory. The aetiology of the disease is still unknown, but aberrant neurotransmitter actions have been hypothesized to underlie the symptoms of schizophrenia. The dopaminergic hypothesis is one most often considered; it proposes that hyperactivity of dopamine transmission is responsible for the positive symptoms observed in schizophrenic patients. This hypothesis is based on the observation that dopamine enhancing drugs, such as amphetamine or cocaine, may induce psychosis, and on the correlation that exists between clinical doses of antipsychotics and their potency in blocking dopamine D2 receptors. All marketed antipsychotics mediate their therapeutic efficacy against positive symptoms by blocking the dopamine D2 receptor. Apart from the clinical efficacy, it appears that the major side effects of antipsychotics, such as extrapyramidal symptoms (EPS) and tardive dyskinesia, are also related to dopamine antagonism. Those debilitating side effects appear most frequently with the typical or first generation of antipsychotic (e.g., haloperidol). They are less pronounced with the atypical or second generation of antipsychotic (e.g., risperidone, olanzapine) and even virtually absent with clozapine, which is considered the prototypical atypical antipsychotic. Among the different theories proposed for explaining the lower incidence of EPS observed with atypical antipsychotics, the one that has caught a lot of attention during the last fifteen years, is the multireceptor hypothesis. It follows from receptor binding studies showing that many atypical antipsychotics interact with various other neurotransmitter receptors in addition to dopamine D2 receptors, in particular with the serotonin 5-HT2 receptors, whereas typical antipsychotic like haloperidol bind more selectively to the D2 receptors. This theory has been challenged in recent years because all major atypical antipsychotics fully occupy the serotonin 5-HT2 receptors at clinically relevant dosages but still differ in inducing motor side-effects. As an alternative to the multireceptor hypothesis, Kapur and Seeman (“Does fast dissociation from the dopamine D2 receptor explain the action of atypical antipsychotics?: A new hypothesis”, Am. J. Psychiatry 2001, 158:3 p. 360-369) have proposed that atypical antipsychotics can be distinguished from typical antipsychotics by the rates at which they dissociate from dopamine D2 receptors. The fast dissociation from the D2 receptor would make an antipsychotic more accommodating of physiological dopamine transmission, permitting an antipsychotic effect without motor side effects. This hypothesis is particularly convincing when one considers clozapine and quetiapine. These two drugs have the fastest rate of dissociation from dopamine D2 receptors and they carry the lowest risk of inducing EPS in humans. Conversely, typical antipsychotics associated with a high prevalence of EPS, are the slowest dissociating dopamine D2 receptor antagonists. Therefore, identifying new drugs based on their rate of dissociation from the D2 receptor appears a valid strategy to provide new atypical antipsychotics.
[0003] As stated previously, current atypical antipsychotics interact with many different neurotransmitter receptors. Some of these interactions (such as the blockade of serotonin 5-HT6 and dopamine D3 receptors) may be beneficial when cognitive impairment and negative symptoms are considered. Indeed, numerous preclinical data have shown that 5-HT6 receptor antagonism has positive effects on cognitive processes in rodents (Mitchell and Neumaier (2005) 5-HT6 receptors: a novel target for cognitive enhancement. Pharmacology & Therapeutics 108:320-333). 5-HT6 antagonism has also been linked to appetite and food intake suppression. Further, D3 receptor antagonism enhances social interaction in rats suggesting a possible benefit on negative symptoms in schizophrenic patients (Joyce and Millan (2005) Dopamine D3 receptor antagonist as therapeutic agents. Drug Discovery Today 10: 917-925). On the other hand, other interactions (such as with adrenergic α1, histamine H1 and serotonin 5-HT2C receptors) are implicated in mediating side-effects, including hypotension, sedation, metabolic disorders and weight gain. Therefore, an additional goal is to combine fast dissociating D2 receptor properties with inhibition of serotonin 5-HT6 and dopamine D3 receptors in the absence of interactions with adrenergic α1, histamine H1 and serotonin 5-HT2C receptors. Such a profile is expected to provide novel compounds efficacious against positive symptoms, negative symptoms and cognitive deficits while having less or none of the major side-effects associated with current antipsychotics.
[0004] It is the object of the present invention to provide novel compounds that are fast dissociating dopamine 2 receptor antagonists as well as serotonin 5-HT6 and dopamine D3 receptor antagonists which have an advantageous pharmacological profile as explained hereinbefore, in particular reduced motor side effects, and moderate or negligible interactions with other receptors resulting in reduced risk of developing metabolic disorders.
[0005] This goal is achieved by the present novel compounds according to Formula (I):
[0000]
[0000] and stereoisomeric forms thereof, wherein
R 1 is chloro, trifluoromethyl or cyano; R 2 is phenyl; phenyl substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halo, cyano, C 1-4 alkyl, C 1-4 alkyloxy, C 1-4 alkylsulfonyl, perfluoroC 1-4 alkyl, perfluoroC 1-4 alkyloxy, diC 1-4 alkylamino, hydroxyl, and phenyl optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halo, C 1-4 alkyl and perfluoroC 1-4 alkyl; thienyl; thienyl substituted with 1 or 2 substituents each independently selected from the group consisting of halo and C 1-4 alkyl; naphthyl; pyridinyl; pyrrolyl; benzothiazolyl; indolyl; quinolinyl; C 3-8 cycloalkyl; or C 5-7 cycloalkenyl; R 3 is hydrogen, C 1-4 alkyl, C 1-4 alkyloxy or halo; R 4 and R 5 are each independently hydrogen or C 1-4 alkyl, or R 4 and R 5 together form C 1-4 alkanediyl; n is 1 or 2; and R 6 is hydrogen, C 1-4 alkyl, hydroxyC 2-4 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 alkyl, pyridinylmethyl, or phenylmethyl optionally substituted on the phenyl with 1, 2 or 3 substituents each independently selected from the group consisting of halo, cyano, C 1-4 alkyl, C 1-4 alkyloxy, C 1-4 alkylsulfonyl, perfluoroC 1-4 alkyl, perfluoroC 1-4 alkyloxy and diC 1-4 alkylamino; or R 5 and R 6 together form C 2-5 alkanediyl; and the pharmaceutically acceptable salts and solvates thereof.
[0013] The compounds according to the invention are fast dissociating D2 receptor antagonists. In addition, the present compounds have approximately the same affinity for dopamine D3 and serotonin 5-HT6 receptors as to dopamine D2 receptors. Insofar as tested, the compounds are antagonists at the three receptor subtypes. This property renders the compounds according to the invention especially suitable for use as a medicine in the treatment or prevention of schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, shared psychotic disorder, psychotic disorder due to a general medical condition, substance-induced psychotic disorder, psychotic disorder not otherwise specified; psychosis associated with dementia; major depressive disorder, dysthymic disorder, premenstrual dysphoric disorder, depressive disorder not otherwise specified, Bipolar I disorder, bipolar II disorder, cyclothymic disorder, bipolar disorder not otherwise specified, mood disorder due to a general medical condition, substance-induced mood disorder, mood disorder not otherwise specified; generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, acute stress disorder, post-traumatic stress disorder; mental retardation; pervasive developmental disorders; attention deficit disorders, attention-deficit/hyperactivity disorder, disruptive behaviour disorders; personality disorder of the paranoid type, personality disorder of the schizoid type, personality disorder of the schizotypical type; tic disorders, Tourette's syndrome; substance dependence; substance abuse; substance withdrawal; trichotillomania; and conditions wherein cognition is impaired; Alzheimer's disease, Parkinson's disease, Huntingdon's disease, Lewy Body Dementia, dementia due to HIV disease, dementia due to Creutzfeldt-Jakob disease; amnestic disorders; mild cognitive impairment; and age-related cognitive decline; and feeding disorders such as anorexia and bulimia; and obesity.
[0014] A skilled person can make a selection of compounds based on the experimental data provided in the Experimental Part hereinafter. Any selection of compounds is embraced within this invention.
[0015] The invention relates to compounds of Formula (I) and stereoisomeric forms thereof, wherein
R 1 is chloro, trifluoromethyl or cyano; R 2 is phenyl; phenyl substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halo, cyano, C 1-4 alkyl, C 1-4 alkyloxy, C 1-4 alkylsulfonyl, perfluoroC 1-4 alkyl, perfluoroC 1-4 alkyloxy, diC 1-4 alkylamino, hydroxyl, and phenyl substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halo, C 1-4 alkyl and perfluoroC 1-4 alkyl; thienyl; thienyl substituted with 1 or 2 substituents each independently selected from the group consisting of halo and C 1-4 alkyl; naphthyl; pyridinyl; pyrrolyl; benzothiazolyl; indolyl; quinolinyl; C 3-8 cycloalkyl; or C 5-7 cycloalkenyl; R 3 is hydrogen, C 1-4 alkyl or halo; R 4 and R 5 are each independently hydrogen or C 1-4 alkyl, or R 4 and R 5 together form C 1-4 alkanediyl; n is 1 or 2; and R 6 is hydrogen, C 1-4 alkyl, hydroxyC 2-4 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkylC 1-4 alkyl, or phenylmethyl substituted on the phenyl with 1, 2 or 3 substituents each independently selected from the group consisting of halo, cyano, C 1-4 alkyl, C 1-4 alkyloxy, C 1-4 alkylsulfonyl, perfluoroC 1-4 alkyl, perfluoroC 1-4 alkyloxy and diC 1-4 alkylamino; or R 5 and R 6 together form C 2-5 alkanediyl;
and the pharmaceutically acceptable salts and solvates thereof.
[0022] For example, the invention relates to compounds of Formula (I) and stereoisomeric forms thereof, wherein
R 1 is trifluoromethyl or cyano; R 2 is phenyl; phenyl substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halo, cyano, C 1-4 alkyl, C 1-4 alkyloxy, C 1-4 alkylsulfonyl, perfluoroC 1-4 alkyl, diC 1-4 alkylamino, hydroxyl, and phenyl substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halo, C 1-4 alkyl and perfluoroC 1-4 alkyl; thienyl; thienyl substituted with 1 or 2 substituents each independently selected from the group consisting of halo and C 1-4 alkyl; naphthyl; pyridinyl; pyrrolyl; benzothiazolyl; indolyl; quinolinyl; C 3-8 cycloalkyl; or C 5-7 cycloalkenyl; R 3 is hydrogen; R 4 and R 5 are each independently hydrogen or C 1-4 alkyl; n is 1; R 6 is hydrogen, methyl, ethyl, cyclopropyl, or phenylmethyl substituted on the phenyl with 1, 2 or 3 substituents each independently selected from the group consisting of halo, cyano, C 1-4 alkyl, C 1-4 alkyloxy, C 1-4 alkylsulfonyl, perfluoroC 1-4 alkyl and diC 1-4 alkylamino; or R 5 and R 6 together form C 2-5 alkanediyl; and the pharmaceutically acceptable salts and solvates thereof.
[0030] Of particular interest are compounds of Formula (I) and stereoisomeric forms thereof wherein
R 1 is trifluoromethyl; R 2 is phenyl; phenyl substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halo, cyano, C 1-4 alkyl, C 1-4 alkyloxy, C 1-4 alkylsulfonyl, perfluoroC 1-4 alkyl, diC 1-4 alkylamino, hydroxyl, and phenyl substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halo, C 1-4 alkyl and perfluoroC 1-4 alkyl; thienyl; thienyl substituted with 1 or 2 substituents each independently selected from the group consisting of halo and C 1-4 alkyl; naphthyl; pyridinyl; pyrrolyl; benzothiazolyl; indolyl; quinolinyl; C 3-8 cycloalkyl; or C 5-7 cycloalkenyl; R 3 is hydrogen; R 4 and R 5 are each independently hydrogen or methyl; n is 1; R 6 is hydrogen, ethyl or (3,5-difluorophenyl)methyl; or R 5 and R 6 together form 1,3-propanediyl; and the pharmaceutically acceptable salts and solvates thereof.
[0039] Amongst the compounds of Formula (I) and the stereoisomeric forms thereof, the most interesting are, for example,
4-Phenyl-6-piperazin-1-yl-3-trifluoromethyl-pyridazine (E1), 6-(4-Ethylpiperazin-1-yl)-4-phenyl-3-trifluoromethyl-pyridazine (E2), 6-[4-(3,5-Difluorobenzyl)piperazin-1-yl]-4-phenyl-3-trifluoromethyl-pyridazine (E3), 6-(3,5-Dimethylpiperazin-1-yl)-4-phenyl-3-trifluoromethyl-pyridazine (E4), 2-(5-Phenyl-6-trifluoromethyl-pyridazin-3-yl)-octahydro-pyrrolo[1,2-c]pyrazine (E5), 4-(4-Fluorophenyl)-6-piperazin-1-yl-3-trifluoromethyl-pyridazine (E6), 6-piperazin-1-yl-4-thiophen-3-yl-3-trifluoromethyl-pyridazine (E7), 6-piperazin-1-yl-4-o-tolyl-3-trifluoromethyl-pyridazine (E8), 4-(4′-Fluorobiphenyl-4-yl)-6-piperazin-1-yl-3-trifluoromethyl-pyridazine (E9) and 4-Phenyl-6-piperazin-1-yl-pyridazine-3-carbonitrile (E10) and the pharmaceutically acceptable salts and solvates thereof.
[0051] Throughout this application, the term “C 1-4 alkyl” when used alone and when used in combinations such as “C 1-4 alkyloxy”, “perfluoroC 1-4 alkyl”, “diC 1-4 alkylamino”, includes, for example, methyl, ethyl, propyl, butyl, 1-methylpropyl, 1,1-dimethylethyl, the term; “perfluoroC 1-4 alkyl” includes for example trifluoromethyl, pentafluoroethyl, heptafluoropropyl and nonafluorobutyl; C 3-8 cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl; C 5-7 cycloalkenyl includes cyclopentenyl, cyclohexenyl and cycloheptenyl. The term halo includes fluoro, chloro, bromo, and iodo.
[0052] The pharmaceutically acceptable salts are defined to comprise the therapeutically active non-toxic acid addition salts forms that the compounds according to Formula (I) are able to form. Said salts can be obtained by treating the base form of the compounds according to Formula (I) with appropriate acids, for example inorganic acids, for example hydrohalic acid, in particular hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid and phosphoric acid; organic acids, for example acetic acid, hydroxyacetic acid, propanoic acid, lactic acid, pyruvic acid, oxalic acid, malonic acid, succinic acid, maleic acid, mandelic acid, fumaric acid, malic acid, tartaric acid, citric acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, cyclamic acid, salicylic acid, p-aminosalicylic acid, pamoic acid and mandelic acid. Conversely, said salts forms can be converted into the free forms by treatment with an appropriate base.
[0053] The term solvates refers to hydrates and alcoholates which the compounds of Formula (I) may form.
[0054] The term “stereochemically isomeric forms” as used hereinbefore defines all the possible isomeric forms that the compounds of Formula (I) may possess. Unless otherwise mentioned or indicated, the chemical designation of compounds denotes the mixture of all possible stereochemically isomeric forms, said mixtures containing all diastereomers and enantiomers of the basic molecular structure. More in particular, stereogenic centers may have the R- or S-configuration; substituents on bivalent cyclic (partially) saturated radicals may have either the cis- or trans-configuration. Compounds encompassing double bonds can have an E or Z-stereochemistry at said double bond. Stereochemically isomeric forms of the compounds of Formula (I) are embraced within the scope of this invention.
[0055] The compounds of Formula (I) as prepared in the processes described below may be synthesized in the form of racemic mixtures of enantiomers that can be separated from one another following art-known resolution procedures. The racemic compounds of Formula (I) may be converted into the corresponding diastereomeric salt forms by reaction with a suitable chiral acid. Said diastereomeric salt forms are subsequently separated, for example, by selective or fractional crystallization and the enantiomers are liberated therefrom by alkali. An alternative manner of separating the enantiomeric forms of the compounds of Formula (I) involves liquid chromatography using a chiral stationary phase. Said pure stereochemically isomeric forms may also be derived from the corresponding pure stereochemically isomeric forms of the appropriate starting materials, provided that the reaction occurs stereospecifically. Preferably if a specific stereoisomer is desired, said compound would be synthesized by stereospecific methods of preparation. These methods will advantageously employ enantiomerically pure starting materials.
Pharmacology
[0056] In order to find antipsychotic compounds active against positive and negative symptoms and cognitive impairment, and having an improved safety profile (low EPS incidence and no metabolic disorders), we have screened for compounds selectively interacting with the dopamine D2 receptor and dissociating fast from this receptor, and further having affinity for the dopamine D3 receptor as well as the serotonin 5-HT-6 receptor. Compounds were first screened for their D2 affinity in a binding assay using [ 3 H]spiperone and human D2L receptor cell membranes. The compounds showing an IC 50 less than 10 μM were tested in an indirect assay adapted from a method published by Josee E. Leysen and Walter Gommeren, Journal of Receptor Research, 1984, 4(7), 817-845, to evaluate their rate of dissociation.
[0057] The compounds were further screened in a panel of more than 50 common G-protein coupled receptors (CEREP) and found to have a clean profile, that is to have low affinity for the tested receptors, with the exception of the dopamine D3 receptor and the serotonin 5-HT6 receptor.
[0058] Some of the compounds have been further tested in in vivo models such as the “Antagonism of apomorphine induced agitation test in rats” and found to be orally active and bio-available.
[0059] Compound E1 was further found to be active in the ‘Reversal of subchronic PCP-induced attentional set shifting in rats’ test (J. S. Rodefer et al., Neurospychopharmacology (2007), 1-10).
[0060] In view of the aforementioned pharmacology of the compounds of Formula (I), it follows that they are suitable for use as a medicine, in particular for use as an antipsychotic. More especially the compounds are suitable for use as a medicine in the treatment or prevention of schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, shared psychotic disorder, psychotic disorder due to a general medical condition, substance-induced psychotic disorder, psychotic disorder not otherwise specified; psychosis associated with dementia; major depressive disorder, dysthymic disorder, premenstrual dysphoric disorder, depressive disorder not otherwise specified, Bipolar I disorder, bipolar II disorder, cyclothymic disorder, bipolar disorder not otherwise specified, mood disorder due to a general medical condition, substance-induced mood disorder, mood disorder not otherwise specified; generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, acute stress disorder, post-traumatic stress disorder; mental retardation; pervasive developmental disorders; attention deficit disorders, attention-deficit/hyperactivity disorder, disruptive behaviour disorders; personality disorder of the paranoid type, personality disorder of the schizoid type, personality disorder of the schizotypical type; tic disorders, Tourette's syndrome; substance dependence; substance abuse; substance withdrawal; trichotillomania. In view of their 5-HT6 antagonistic activity, the compounds of the present invention may further be useful for the treatment or prophylaxis of conditions wherein cognition is impaired; Alzheimer's disease, Parkinson's disease, Huntingdon's disease, Lewy Body Dementia, dementia due to HIV disease, dementia due to Creutzfeldt-Jakob disease; amnestic disorders; mild cognitive impairment; and age-related cognitive decline.
[0061] To optimize treatment of patients suffering from a disorder as mentioned in the foregoing paragraph, the compounds of Formula (I) may be administered together with other psychotropic compounds. Thus, in the case of schizophrenia, negative and cognitive symptoms may be targeted.
[0062] The present invention also provides a method of treating warm-blooded animals suffering from such disorders, said method comprising the systemic administration of a therapeutic amount of a compound of Formula (I) effective in treating the above described disorders.
[0063] The present invention also relates to the use of compounds of Formula (I) as defined hereinabove for the manufacture of a medicament, in particular an antipsychotic medicament, more especially a medicine in the treatment or prevention of schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, shared psychotic disorder, psychotic disorder due to a general medical condition, substance-induced psychotic disorder, psychotic disorder not otherwise specified; psychosis associated with dementia; major depressive disorder, dysthymic disorder, premenstrual dysphoric disorder, depressive disorder not otherwise specified, Bipolar I disorder, bipolar II disorder, cyclothymic disorder, bipolar disorder not otherwise specified, mood disorder due to a general medical condition, substance-induced mood disorder, mood disorder not otherwise specified; generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, acute stress disorder, post-traumatic stress disorder; mental retardation; pervasive developmental disorders; attention deficit disorders, attention-deficit/hyperactivity disorder, disruptive behaviour disorders; personality disorder of the paranoid type, personality disorder of the schizoid type, personality disorder of the schizotypical type; tic disorders, Tourette's syndrome; substance dependence; substance abuse; substance withdrawal; trichotillomania; and conditions wherein cognition is impaired; Alzheimer's disease, Parkinson's disease, Huntingdon's disease, Lewy Body Dementia, dementia due to HIV disease, dementia due to Creutzfeldt-Jakob disease; amnestic disorders; mild cognitive impairment; and age-related cognitive decline.
[0064] Those of skill in the treatment of such diseases could determine the effective therapeutic daily amount from the test results presented hereinafter. An effective therapeutic daily amount would be from about 0.01 mg/kg to about 10 mg/kg body weight, more preferably from about 0.05 mg/kg to about 1 mg/kg body weight.
[0065] The invention also relates to a pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound according to Formula (I).
[0066] For ease of administration, the subject compounds may be formulated into various pharmaceutical forms for administration purposes. The compounds according to the invention, in particular the compounds according to Formula (I), a pharmaceutically acceptable acid or base addition salt thereof, a stereochemically isomeric form thereof, an N-oxide form thereof and a prodrug thereof, or any subgroup or combination thereof may be formulated into various pharmaceutical forms for administration purposes. As appropriate compositions there may be cited all compositions usually employed for systemically administering drugs. To prepare the pharmaceutical compositions of this invention, an effective amount of the particular compound, optionally in addition salt form, as the active ingredient is combined in intimate admixture with a pharmaceutically acceptable carrier, which carrier may take a wide variety of forms depending on the form of preparation desired for administration. These pharmaceutical compositions are desirable in unitary dosage form suitable, in particular, for administration orally, rectally, percutaneously, by parenteral injection or by inhalation. For example, in preparing the compositions in oral dosage form, any of the usual pharmaceutical media may be employed such as, for example, water, glycols, oils, alcohols and the like in the case of oral liquid preparations such as suspensions, syrups, elixirs, emulsions and solutions; or solid carriers such as starches, sugars, kaolin, diluents, lubricants, binders, disintegrating agents and the like in the case of powders, pills, capsules and tablets. Because of their ease in administration, tablets and capsules represent the most advantageous oral dosage unit forms in which case solid pharmaceutical carriers are obviously employed. For parenteral compositions, the carrier will usually comprise sterile water, at least in large part, though other ingredients, for example, to aid solubility, may be included. Injectable solutions, for example, may be prepared in which the carrier comprises saline solution, glucose solution or a mixture of saline and glucose solution. Injectable solutions, for example, may be prepared in which the carrier comprises saline solution, glucose solution or a mixture of saline and glucose solution. Injectable solutions containing compounds of Formula (I) may be formulated in an oil for prolonged action. Appropriate oils for this purpose are, for example, peanut oil, sesame oil, cottonseed oil, corn oil, soybean oil, synthetic glycerol esters of long chain fatty acids and mixtures of these and other oils. Injectable suspensions may also be prepared in which case appropriate liquid carriers, suspending agents and the like may be employed. Also included are solid form preparations that are intended to be converted, shortly before use, to liquid form preparations. In the compositions suitable for percutaneous administration, the carrier optionally comprises a penetration enhancing agent and/or a suitable wetting agent, optionally combined with suitable additives of any nature in minor proportions, which additives do not introduce a significant deleterious effect on the skin. Said additives may facilitate the administration to the skin and/or may be helpful for preparing the desired compositions. These compositions may be administered in various ways, e.g., as a transdermal patch, as a spot-on, as an ointment. Acid or base addition salts of compounds of Formula (I) due to their increased water solubility over the corresponding base or acid form, are more suitable in the preparation of aqueous compositions.
[0067] It is especially advantageous to formulate the aforementioned pharmaceutical compositions in unit dosage form for ease of administration and uniformity of dosage. Unit dosage form as used herein refers to physically discrete units suitable as unitary dosages, each unit containing a predetermined quantity of active ingredient calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. Examples of such unit dosage forms are tablets (including scored or coated tablets), capsules, pills, powder packets, wafers, suppositories, injectable solutions or suspensions and the like, and segregated multiples thereof.
[0068] Since the compounds according to the invention are potent orally administrable compounds, pharmaceutical compositions comprising said compounds for administration orally are especially advantageous.
[0069] In order to enhance the solubility and/or the stability of the compounds of Formula (I) in pharmaceutical compositions, it can be advantageous to employ α-, β- or γcyclodextrins or their derivatives, in particular hydroxyalkyl substituted cyclodextrins, e.g. 2-hydroxypropyl-β-cyclodextrin. Also co-solvents such as alcohols may improve the solubility and/or the stability of the compounds according to the invention in pharmaceutical compositions.
Preparation
[0070] Compounds of Formula (I) wherein R 1 is chloro or trifluoromethyl and R 2 , R 3 , R 4 , R 5 , R 6 and n are as defined before, can be prepared by reacting a compound of Formula (II)
[0000]
[0000] where R 1 is chloro or trifluoromethyl and R 2 and R 3 are as defined before, with a compound of Formula (III)
[0000]
[0000] where R 4 , R 5 , R 6 and n are as defined before, in the presence of a suitable base, such as diisopropylethylamine, in a suitable solvent, such as acetonitrile and under suitable reaction conditions, such as a convenient temperature, either by conventional heating or under microwave irradiation for a period of time to ensure the completion of the reaction.
[0071] Compounds of Formula (II) wherein R 1 is chloro and R 2 and R 3 are as defined before, may be prepared by procedures similar to those described in WO-2005/013907.
[0072] Compounds of Formula (II) wherein R 1 is trifluoromethyl and R 2 and R 3 are as defined before, can be prepared by reacting a compound of Formula (IV)
[0000]
[0000] where R 1 is trifluoromethyl and R 2 and R 3 are as defined before, with phosphorous oxychloride, in a suitable solvent, such as acetonitrile, under suitable reaction conditions, such as a convenient temperature, either by conventional heating or under microwave irradiation for a period of time to ensure the completion of the reaction.
[0073] Compounds of Formula (IV) wherein R 1 is trifluoromethyl and R 2 and R 3 are as defined before, can be prepared by reacting a compound of Formula (V)
[0000]
[0000] where R 1 is trifluoromethyl and R 2 and R 3 are as defined before, with hydrazine hydrate, in the presence of a suitable catalyst, such as acetic acid, in a suitable solvent, such as acetonitrile, under suitable reaction conditions, such as a convenient temperature, either by conventional heating or under microwave irradiation for a period of time to ensure the completion of the reaction.
[0074] Compounds of Formula (V) wherein R 1 is trifluoromethyl and R 2 and R 3 are as defined before, may be prepared by reacting a compound of Formula (VI)
[0000]
[0075] where R 2 and R 3 are as defined before, with CF 3 SiMe 3 (VII), in the presence of a suitable catalyst, such as cesium fluoride, in a suitable solvent, such as acetonitrile, under suitable reaction conditions, such as low temperatures, typically ranging between −78° C. and 0° C.
[0076] Compounds of Formula (VI) where R 2 and R 3 are as defined before, can be obtained commercially or by procedures similar to those described in Dean, W. D.; Bum, D. M. J. Org. Chem. 1993, 58, 7916-7917.
Compounds of Formula (I-a)
[0077]
[0000] wherein R 6′ is R 6 as defined before but not hydrogen, R 1 is chloro or trifluoromethyl and R 2 , R 3 , R 4 , R 5 and n are as defined before, can also be prepared by reacting compounds of Formula (I-b)
[0000]
[0000] wherein R 1 is chloro or trifluoromethyl and R 2 , R 3 , R 4 , R 5 and n are as defined before, with a reagent of R 6′ —W wherein R 6′ is R 6 as defined before but not hydrogen and W represents a leaving group such as halo, e.g. chloro, bromo or iodo, or a sulfonyloxy group, e.g. methylsulfonyloxy, trifluoromethylsulfonyloxy, or methylphenylsulfonyloxy in the presence of a base such as diisopropylethylamine, in a suitable solvent such as acetonitrile and under suitable reaction conditions, such as a convenient temperature, either by conventional heating or under microwave irradiation for a period of time to ensure the completion of the reaction.
[0078] Alternatively, the compounds of Formula (I-a) wherein R 6′ is R 6 as defined before but not hydrogen, R 1 is chloro or trifluoromethyl and R 2 , R 3 , R 4 , R 5 and n are as defined before, can also be prepared from a compound of Formula (I-b) wherein R 1 is chloro or trifluoromethyl and R 2 , R 3 , R 4 , R 5 and n are as defined before, by reductive N-alkylation with an appropriate ketone or aldehyde in the presence of a suitable reducing agent such as sodium triacetoxyborohydride in a suitable solvent such as tetrahydrofuran.
[0079] Compounds of Formula (I-b) wherein R 1 is chloro or trifluoromethyl and R 2 , R 3 , R 4 , R 5 and n are as defined before, may be prepared by deprotection of the protecting group in an intermediate of Formula (VIII)
[0000]
[0000] where L represents a suitable protecting group, such as tert-butyloxycarbonyl, R 1 is chloro or trifluoromethyl and R 2 , R 3 , R 4 , R 5 and n are as defined before, under suitable conditions, such as trifluoroacetic acid in dichloromethane or Amberlyst® 15 ion exchange resin, acidic form in methanol when L represents a tert-butyloxycarbonyl group.
[0080] Compounds of Formula (VIII) wherein R 1 is chloro or trifluoromethyl and R 2 , R 3 , R 4 , R 5 and n are as defined before, can be prepared by reacting a compound of Formula (II) where R 1 is chloro or trifluoromethyl and R 2 and R 3 are as defined before, with a compound of Formula (IX)
[0000]
[0000] where L represents a suitable protecting group, such as tert-butyloxycarbonyl and R 4 , R 5 and n are as defined before, in the presence of a suitable base, such as diisopropylethylamine, in a suitable solvent, such as acetonitrile and under suitable reaction conditions, such as a convenient temperature, either by conventional heating or under microwave irradiation for a period of time to ensure the completion of the reaction.
[0081] Compounds of Formula (VIII) wherein R 1 is trifluoromethyl and R 2 , R 3 , R 4 , R 5 and n are as defined before and L represents a suitable protecting group, such as tert-butyloxycarbonyl, can also be prepared by reacting a compound of Formula (X)
[0000]
[0000] where R 1 is trifluoromethyl and R 3 , R 4 , R 5 and n are as defined before and L represents a suitable protecting group, such as tert-butyloxycarbonyl, with a corresponding arylboronic acid R 2 —B(OH) 2 in the presence of a suitable catalyst such as 1,1′-bis(diphenylphosphino)ferrocenepalladium(II).dichloride, dichloromethane in the presence of suitable ligand such as 1,1′-bis(diphenylphosphino)ferrocene and a base such as potassium phosphate in a suitable inert solvent such as dioxane at an elevated temperature.
[0082] Compounds of Formula (X) wherein R 1 is trifluoromethyl and R 3 , R 4 , R 5 and n are as defined before and L represents a suitable protecting group, such as tert-butyloxycarbonyl, may be prepared by reacting a compound of Formula (XI)
[0000]
[0000] where R 1 is trifluoromethyl, and, R 3 , R 4 , R 5 and n are as defined before and L represents a suitable protecting group, such as tert-butyloxycarbonyl, with iodine in the presence of a suitable base such as a mixture of buthyllithium and 2,2,6,6-tetramethylpiperidine in a suitable inert solvent such as tetrahydrofuran at low temperatures, typically ranging from −78° C. to 0° C.
[0083] Compounds of Formula (XI) wherein R 1 is trifluoromethyl, R 3 , R 4 , R 5 and n are as defined before and L represents a suitable protecting group, such as tert-butyloxycarbonyl, may be prepared by reacting 6-chloro-3-trifluoromethylpyridazine (prepared by following the procedure described in Goodman, A. J.; Stanforth, S. P; Tarbit B. Tetrahedron 1999, 55, 15067-15070) with tent-butyl 1-piperazinecarboxylate in the presence of a suitable base such as diisopropylethylamine in a suitable solvent such as acetonitrile at a convenient temperature, either by conventional heating or under microwave irradiation for a period of time to ensure the completion of the reaction.
[0084] Compounds of Formula (I-c) wherein R 6′ is R 6 as defined before but not hydrogen, R 1 is trifluoromethyl, R 3 , R 4 , R 5 , R 7 and n are as defined before,
[0000]
[0000] can be prepared by reacting a compound of Formula (I-d)
[0000]
[0000] wherein R 1 is trifluoromethyl, R 3 , R 4 , R 5 , R 7 and n are as defined before, with a reagent of Formula R 6′ —W wherein R 6′ is R 6 as defined before but not hydrogen and W represents a leaving group such as halo, e.g. chloro, bromo or iodo, or a sulfonyloxy group, e.g. methylsulfonyloxy, trifluoromethylsulfonyloxy or methylphenylsulfonyloxy in the presence of a base such as diisopropylethylamine, in a suitable solvent such as acetonitrile and under suitable reaction conditions, such as a convenient temperature, either by conventional heating or under microwave irradiation for a period of time to ensure the completion of the reaction.
[0085] Alternatively, the compounds of Formula (I-c) wherein R 6′ is R 6 as defined before but not hydrogen, R 1 is trifluoromethyl, R 3 , R 4 , R 5 , R 7 and n are as defined before, can be prepared from a compound of Formula (I-d) wherein R 1 is trifluoromethyl, R 3 , R 4 , R 5 , R 7 and n are as defined before, by reductive N-alkylation with an appropriate ketone or aldehyde in the presence of a suitable reducing agent such as sodium triacetoxyborohydride in a suitable solvent such as tetrahydrofuran.
[0086] Compounds of Formula (I-d) wherein R 1 is trifluoromethyl, R 3 , R 4 , R 5 , R 7 and n are as defined before, may be prepared by deprotection of the protecting group in an intermediate of Formula (XII)
[0000]
[0000] where R 1 is trifluoromethyl, R 3 , R 4 , R 5 , R 7 and n are as defined before and L represents a suitable protecting group, such as tert-butyloxycarbonyl, under suitable conditions, such as trifluoroacetic acid in dichloromethane or Amberlyst® 15 ion exchange resin, acidic form in methanol when L represents a tert-butyloxycarbonyl group.
[0087] Compounds of Formula (XII) wherein R 1 is trifluoromethyl, R 3 , R 4 , R 5 , R 7 and n are as defined before and L represents a suitable protecting group, such as tert-butyloxycarbonyl can be prepared by reacting a compound of Formula (XIII)
[0000]
[0000] wherein R 1 is trifluoromethyl, R 3 , R 4 , R 5 and n are as defined before and L represents a suitable protecting group, such as tert-butyloxycarbonyl, with a corresponding arylboronic acid in the presence of a suitable catalyst such as trans-Pd(OAc) 2 (Cy 2 NH) 2 (prepared by following the procedure described in Tao, B.; Boykin, D. W. Tetrahedron Lett. 2003, 44, 7993-7996) in the presence of suitable base such as potassium phosphate in a suitable inert solvent such as dioxane, under suitable reaction conditions, such as a convenient temperature, either by conventional heating or under microwave irradiation for a period of time to ensure the completion of the reaction.
[0088] Compounds of Formula (I) wherein R 1 is cyano, R 6 is as defined before but not hydrogen, R 2 , R 3 , R 4 , R 5 and n are as described before, can be prepared by reacting a compound of Formula (I-e)
[0000]
[0000] wherein and R 2 , R 3 , R 4 , R 5 and n are as described before, with a reagent of Formula R 6′ —W wherein R 6′ is R 6 as defined before but not hydrogen and W represents a leaving group such as halo, e.g. chloro, bromo or iodo, or a sulfonyloxy group, e.g. methylsulfonyloxy, trifluoromethylsulfonyloxy or methylphenylsulfonyloxy in the presence of a base such as diisopropylethylamine, in a suitable solvent such as acetonitrile and under suitable reaction conditions, such as a convenient temperature, either by conventional heating or under microwave irradiation for a period of time to ensure the completion of the reaction.
[0089] Alternatively, the compounds of Formula (I) wherein R 1 is cyano, R 6′ is R 6 but other than hydrogen, and R 2 , R 3 , R 4 , R 5 and n are as described before, can be prepared from a compound of Formula (I-e) wherein R 1 is cyano, R 6′ is hydrogen, and R 2 , R 3 , R 4 , R 5 and n are as described before, by reductive N-alkylation with an appropriate ketone or aldehyde in the presence of a suitable reducing agent in a suitable solvent.
[0090] Compounds of Formula (I) wherein R 1 is cyano, R 6 is as defined before, and R 2 , R 3 , R 4 , R 5 and n are as described before, may be prepared by deprotection of the protecting group in an intermediate of Formula (XIV)
[0000]
[0000] where R 2 , R 3 , R 4 , R 5 and n are as described before and L represents a suitable protecting group, such as tert-butyloxycarbonyl, under suitable conditions, such as trifluoroacetic acid in dichloromethane or Amberlyst® 15 ion exchange resin, acidic form in methanol when L represents a tert-butyloxycarbonyl group.
[0091] Compounds of Formula (XIV) wherein R 2 , R 3 , R 4 , R 5 and n are as described before and L represents a suitable protecting group, such as tert-butyloxycarbonyl, were prepared by reacting a compound of Formula (VIII) wherein R 1 is chloro, and R 2 , R 3 , R 4 , R 5 and n are as described before and L represents a suitable protecting group, such as tert-butyloxycarbonyl, with zinc cyanide in the presence of a suitable catalyst, such as tetrakis(triphenylphosphine)palladium (0) in a suitable solvent, such as N,N-dimethylformamide under suitable reaction conditions, such as a convenient temperature, either by conventional heating or under microwave irradiation for a period of time to ensure the completion of the reaction.
Experimental Part
Chemistry
[0092] Microwave assisted reactions were performed in a single-mode reactor: Emrys™ Optimizer microwave reactor (Personal Chemistry A.B., currently Biotage).
[0093] Final purification of Examples (E1-E 39) was carried out either by column chromatography on silica gel using the eluent described or by reversed phase preparative HPLC on a Hyperprep RP 18 BDS (Shandon) (8 μm, 200 mm, 250 g) column. Three mobile phases (mobile phase A: 90% 0.5% ammoniumacetate+10% acetonitrile; mobile phase B: methanol; mobile phase C: acetonitrile) were used to run a gradient method starting with 75% A and 25% B with a flow rate of 40 ml/min, hold for 0.5 minutes at the same conditions followed with an increase of the flow rate to 80 ml/min in 0.01 minutes to 50% B and 50% C in 41 minutes, to 100% C in 20 minutes and hold these conditions for 4 minutes.
[0094] 1 H spectra were recorded on a Bruker DPX 360, DPX 400 or a Bruker AV-500 spectrometer. The chemical shifts are expressed in ppm relative to tetramethylsilane.
[0095] Melting point determination was performed on a Mettler FP62 apparatus.
LCMS
General LCMS Method A:
[0096] The HPLC measurement was performed using a HP 1100 from Agilent Technologies comprising a quaternary pump with degasser, an autosampler, a column oven (set at 40° C. except for Method 4 where the temperature was set at 60° C.), a diode-array detector (DAD) and a column as specified in the respective methods below. Flow from the column was split to a MS detector. The MS detector was configured with an electrospray ionization source. Nitrogen was used as the nebulizer gas. The source temperature was maintained at 140° C. Data acquisition was performed with MassLynx-Openlynx software.
General LCMS Method B:
[0097] The HPLC measurement was performed using an Agilent 1100 module comprising a pump, a diode-array detector (DAD) (wavelength used 220 nm), a column heater and a column as specified in the respective methods below. Flow from the column was split to a Agilent MSD Series G1946C and G1956A. MS detector was configured with API-ES (atmospheric pressure electrospray ionization). Mass spectra were acquired by scanning from 100 to 1000. The capillary needle voltage was 2500 V for positive ionization mode and 3000 V for negative ionization mode. Fragmentation voltage was 50V. Drying gas temperature was maintained at 350° C. at a flow of 10 l/min.
LCMS Method 1
[0098] In addition to general LCMS method A: Reversed phase HPLC was carried out on an ACE-C18 column (3.0 μm, 4.6×30 mm) from Advanced Chromatography Technologies, with a flow rate of 1.5 ml/min. The gradient conditions used are: 80% A (0.5 g/l ammonium acetate solution), 10% B (acetonitrile), 10% C (methanol) to 50% B and 50% C in 6.5 minutes, to 100% B at 7 minutes and equilibrated to initial conditions at 7.5 minutes until 9.0 minutes. Injection volume 5 μl. High-resolution mass spectra (Time of Flight, TOF) were acquired only in positive ionization mode by scanning from 100 to 750 in 0.5 seconds using a dwell time of 0.1 seconds. The capillary needle voltage was 2.5 kV for positive ionization mode and the cone voltage was 20 V. Leucine-Enkephaline was the standard substance used for the lock mass calibration.
LCMS Method 2
[0099] In addition to general LCMSmethod A: Reversed phase HPLC was carried out on an ACE-C18 column (3.0 μm, 4.6×30 mm) from Advanced Chromatography Technologies, with a flow rate of 1.5 ml/min. The gradient conditions used are: 80% A (0.5 g/l ammonium acetate solution), 10% B (acetonitrile), 10% C (methanol) to 50% B and 50% C in 6.5 minutes, to 100% B at 7 minutes and equilibrated to initial conditions at 7.5 minutes until 9.0 minutes. Injection volume 5 μl. High-resolution mass spectra (Time of Flight, TOF) were acquired by scanning from 100 to 750 in 0.5 seconds using a dwell time of 0.3 seconds. The capillary needle voltage was 2.5 kV for positive ionization mode and 2.9 kV for negative ionization mode. The cone voltage was 20 V for both positive and negative ionization modes. Leucine-Enkephaline was the standard substance used for the lock mass calibration.
LCMS Method 3
[0100] Same as LCMS Method 1 using 10 μl of injection volume.
LCMS Method 4
[0101] In addition to general LCMS method A: Reversed phase HPLC was carried out on an XDB-C18 cartridge (1.8 μm, 2.1×30 mm) from Agilent, with a flow rate of 1 ml/min. The gradient conditions used are: 90% A (0.5 g/l ammonium acetate solution), 5% B (acetonitrile), 5% C (methanol) to 50% B and 50% C in 6.5 minutes, to 100% B at 7.0 minutes and equilibrated to initial conditions at 7.5 minutes until 9.0 minutes. Injection volume 2 μl. High-resolution mass spectra (Time of Flight, TOF) were acquired only in positive ionization mode by scanning from 100 to 750 in 0.5 seconds using a dwell time of 0.1 seconds. The capillary needle voltage was 2.5 kV and the cone voltage was 20 V. Leucine-Enkephaline was the standard substance used for the lock mass calibration.
LCMS Method 5
[0102] In addition to general LCMS method A: Reversed phase HPLC was carried out on an ACE-C18 column (3.0 μm, 4.6×30 mm) from Advanced Chromatography Technologies, with a flow rate of 1.5 ml/min. The gradient conditions used are: 80% A (1 g/l ammonium bicarbonate solution), 10% B (acetonitrile), 10% C (methanol) to 50% B and 50% C in 6.5 minutes, to 100% B at 7 minutes and equilibrated to initial conditions at 7.5 minutes until 9.0 minutes. Injection volume 5 μl. High-resolution mass spectra (Time of Flight, TOF) were acquired only in positive ionization mode by scanning from 100 to 750 in 0.5 seconds using a dwell time of 0.1 seconds. The capillary needle voltage was 2.5 kV for positive ionization mode and the cone voltage was 20 V. Leucine-Enkephaline was the standard substance used for the lock mass calibration.
LCMS Method 6
[0103] In addition to general LCMS method B: Reversed phase HPLC was carried out on a YMC-Pack ODS-AQ, 50×2.0 mm 5 μm column with a flow rate of 0.8 ml/min. Two mobile phases (mobile phase A: water with 0.1% TFA; mobile phase B: acetonitrile with 0.05% TFA) were used. First, 100% A was held for 1 minute. Then a gradient was applied to 40% A and 60% B in 4 minutes and held for 2.5 minutes. Typical injection volumes of 2 μl were used. Oven temperature was 50° C. (MS polarity: positive)
LCMS Method 7
[0104] In addition to general LCMS method B: Reversed phase HPLC was carried out on a YMC-Pack ODS-AQ, 50×2.0 mm 5 μm column with a flow rate of 0.8 ml/min. Two mobile phases (mobile phase A: water with 0.1% TFA; mobile phase B: acetonitrile with 0.05% TFA) were used. First, 90% A and 10% B was held for 0.8 minutes. Then a gradient was applied to 20% A and 80% B in 3.7 minutes and held for 3 minutes. Typical injection volumes of 2 μl were used. Oven temperature was 50° C.
(MS Polarity: Positive)
Description 1
5,5,5-Trifluoro-4-oxo-3-phenyl-pent-2-enoic acid (D1)
[0105]
[0106] To a stirred solution of phenylmaleic anhydride (18.7 g, 0.107 mol) in acetonitrile (180 ml) at 0° C. (ice/water/sodium chloride bath—temperature of the bath −10° C.), was added CsF (18.6 g, 0.127 mol), followed by the drop-wise addition of CF 3 SiMe 3 (18.58 ml, 0.127 mol), under nitrogen. The reaction mixture was stirred for 1 h, and was then diluted with diethyl ether and extracted with 2M sodium hydroxide (200 ml). The separated aqueous layer was acidified to pH=1 by the addition of conc. hydrochloric acid. This mixture was extracted with dichloromethane. The separated organic layer was dried (Na 2 SO 4 ), and the solvent was evaporated in vacuo to yield D1 (22.6 g, 86%) as a mixture of isomers (80/11 ratio by LCMS). C 11 H 7 F 3 O 3 requires 244; Found 243 (M-H − ).
Description 2
5-Phenyl-6-trifluoromethyl-2H-pyridazine-3-one (D2)
[0107]
[0108] To a stirred solution of 5,5,5-trifluoro-4-oxo-3-phenyl-pent-2-enoic acid (D1) (22.6 g, 0.084 mol) in a mixture of acetonitrile (150 ml) and acetic acid (15 ml), was added hydrazine hydrate (7.75 ml, 0.148 mol). The reaction mixture was heated at reflux for 16 h, cooled to room temperature, diluted with dichloromethane and then extracted with 0.5 M hydrochloric acid (150 ml). The organic layer was separated, dried (Na 2 SO 4 ) and the solvent evaporated in vacuo to yield D2 (20.7 g, 100%) as a mixture of isomers (75/5 ratio by LCMS). C 11 H 7 F 3 N 2 O requires 240; Found 239 (M-H) − .
Description 3
6-Chloro-4-phenyl-3-trifluoromethyl-pyridazine (D3)
[0109]
[0110] To a stirred solution of 5-phenyl-6-trifluoromethyl-2H-pyridazine-3-one (D2) (20.66 g, 0.086 mol) in acetonitrile (150 ml) was added phosphorous oxychloride (20 ml, 0.215 mmol) and the reaction heated at reflux for 1 h. After this period, the reaction mixture was poured into a saturated solution of sodium hydrogen carbonate, ice and dichloromethane. Further solid sodium hydrogen carbonate was then added until gas evolution had ceased. The organic layer was then separated, dried (Na 2 SO 4 ) and the solvents evaporated in vacuo. The crude residue was then filtered through silica gel, eluting with dichloromethane, in order to remove the minor isomer. After evaporation of the solvent, the crude product was then re-purified by column chromatography (silica; 0-25% ethyl acetate/heptane) to yield D3 (7.1 g, 32%). C 11 H 6 ClF 3 N 2 requires 258; Found 259 (MH + ).
Description 4
4-(5-Phenyl-6-trifluoromethyl-pyridazin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester (D4)
[0111]
[0112] To a stirred solution of 6-chloro-4-phenyl-3-trifluoromethyl-pyridazine (D3) (7.1 g, 0.0274 mol) and N-Boc-piperazine (5.62 g, 0.0302 mol) in acetonitrile (150 ml) was added diisopropylethylamine (5.1 ml, 0.0302 mol) and the mixture heated at 150° C. for 20 min., under microwave irradiation. After this period, the reaction mixture was diluted with dichloromethane and extracted with water. The organic layer was separated, dried (MgSO 4 ) and the solvents evaporated in vacuo. The crude product was purified by column chromatography (silica; 20% ethyl acetate in heptane, followed by 10% ethyl acetate in dichloromethane). After evaporation of the solvent, the crude product was crystallised from heptane to yield D4 (10.4 g, 93%). C 20 H 23 F 3 N 4 O 2 requires 408; Found 409 (MH + ).
Description 5
5,5,5-Trifluoro-3-(4-fluorophenyl)-4-oxo-pent-2-enoic acid (D5)
[0113]
[0114] To a stirred solution of 4-fluorophenylmaleic anhydride (1.42 g, 7.39 mmol) (prepared by procedures similar to those described in Dean, W. D.; Bum, D. M. J. Org. Chem. 1993, 58, 7916-7917), in acetonitrile (15 ml) at 0° C. (ice/water/sodium chloride bath—temperature of the bath −10° C.), was added CsF (1.1 g, 7.39 mmol), followed by the drop-wise addition of CF 3 SiMe 3 (1 ml, 7.39 mmol), under nitrogen. The reaction mixture was stirred for 1 h, and then diluted with diethyl ether and extracted with 2M sodium hydroxide (200 ml). The organic layer was removed and the aqueous layer acidified to pH=1 by the addition of conc. hydrochloric acid. The mixture was extracted with dichloromethane and the organic layer removed, dried (Na 2 SO 4 ), and the solvent evaporated in vacuo to yield D5 (1.4 g, 72%) as a mixture of isomers. C 11 H 6 F 4 O 3 requires 262 Found 261 (M-H) − .
Description 6
5-(4-Fluorophenyl)-6-trifluoromethyl-2H-pyridazine-3-one (D6)
[0115]
[0116] To a stirred solution of 5,5,5-trifluoro-3-(4-fluorophenyl)-4-oxo-pent-2-enoic acid (D5) (1.4 g, 5.3 mmol) in a mixture of ethanol (10 ml) and acetic acid (1 ml), was added hydrazine hydrate (0.49 ml, 9.33 mmol). The reaction mixture was heated at reflux for 16 h, cooled to room temperature, diluted with dichloromethane and then extracted with 0.5 M hydrochloric acid (150 ml). The organic layer was separated, dried (Na 2 SO 4 ) and the solvent evaporated in vacuo to yield D6 (0.96 g, 70%) as a mixture of isomers. C 11 H 6 F 4 N 2 O requires 258; Found 259 (MH + ).
Description 7
6-Chloro-4-(4-fluorophenyl)-3-trifluoromethyl-pyridazine (D7)
[0117]
[0118] To a stirred solution of 5-(4-fluorophenyl)-6-trifluoromethyl-2H-pyridazine-3-one (D6) (0.96 g, 3.7 mmol) in acetonitrile (10 ml) was added phosphorous oxychloride (0.866 ml, 9.3 mmol) and the reaction was stirred at 180° C. for 30 min., under microwave irradiation. After this period, the reaction mixture was poured into a saturated solution of sodium hydrogen carbonate, ice and dichloromethane. Further solid sodium hydrogen carbonate was then added until gas evolution had ceased. The organic layer was then separated, dried (Na 2 SO 4 ) and the solvents evaporated in vacuo to yield D7 (0.81 g, 79%). Only traces of the undesired isomer were detected after work-up. C 11 H 5 ClF 4 N 2 requires 276; Found 277 (MH + ).
Description 8
[0119] 4-[5-(4-Fluorophenyl)-6-trifluoromethyl-pyridazin-3-yl]-piperazine-1-carboxylic acid tent-butyl ester (D8)
[0000]
[0120] To a stirred solution of 6-chloro-4-(4-fluorophenyl)-3-trifluoromethyl-pyridazine (D7) (0.81 g, 2.93 mmol) and N-Boc-piperazine (0.818 g, 4.39 mmol) in acetonitrile (10 ml) was added diisopropylethylamine (1 ml, 5.9 mmol) and the mixture was stirred at 80° C. for 30 min., under microwave irradiation. After this period, the reaction mixture was diluted with dichloromethane and extracted with water. The organic layer was separated, dried (MgSO 4 ) and the solvents evaporated in vacuo to yield D8 (1.27 g, 62%) C 20 H 22 F 4 N 4 O 2 requires 426; Found 427 (MH + ).
Description 9
4-(6-Trifluoromethyl-pyridazin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester (D9)
[0121]
[0122] A mixture of 6-chloro-3-trifluoromethylpyridazine (0.666 g, 5.09 mmol) (prepared by following the procedure described in Goodman, A. J.; Stanforth, S. P; Tarbit B. Tetrahedron 1999, 55, 15067-15070), N-Boc-piperazine (1.138 g, 6.11 mmol) and diisopropylethylamine (1.95 ml, 1.12 mmol) in acetonitrile (10 ml) was stirred at 180° C. for 30 min., under microwave irradiation. The solvent was evaporated in vacuo and the residue was purified by column chromatography (silica gel; hexane/ethyl acetate) to yield D9 (1.67 g, 99%) as a light yellow solid. C 14 H 19 F 3 N 4 O 2 requires 332; Found 333 (MH + ).
Description 10
4-(5-Iodo-6-trifluoromethyl-pyridazin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester (D10)
[0123]
[0124] To a mixture of butyllithium (2.5 M in hexanes) (6.31 ml, 15.79 mmol) in tetrahydrofuran (125 ml) at 0° C., was added 2,2,6,6-tetramethylpiperidine (3.808 ml, 22.56 mmol). The reaction mixture was then stirred at room temperature for 1 h. The mixture was cooled to −78° C. and then a solution of 4-(6-trifluoromethyl-pyridazin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester (D9) (2.5 g, 7.52 mmol) in tetrahydrofuran (20 ml) was added. The mixture was stirred for 1 h. at −78° C. before adding a solution of iodine (2.29 g, 9.024 mmol) in tetrahydrofuran (10 ml). The mixture was stirred at −78° C. for 1 h. and then diluted with a 10% solution of acetic acid in tetrahydrofuran. The mixture was then allowed to reach room temperature and then the solvent was evaporated in vacuo. The residue was diluted with dichloromethane and extracted with water. The organic layer was separated, dried (MgSO 4 ), filtered and the solvent evaporated in vacuo. The residue was precipitated from diethyl ether to yield D10 (2.81 g, 82%) as a light yellow solid. C 14 H 18 F 31 N 4 O 2 requires 458; Found 459 (MH + ).
Description 11
4-[5-(2-Tolyl)-6-trifluoromethyl-pyridazin-3-yl]-piperazine-1-carboxylic acid tert-butyl ester (D11)
[0125]
[0126] A mixture of 4-(5-iodo-6-trifluoromethyl-pyridazin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester (D10) (0.20 g, 0.436 mmol), o-tolylboronic acid (0.071 g, 0.523 mmol), 1,1′-bis(diphenylphosphino)ferrocenepalladium(II).dichloride, dichloromethane (0.022 g, 0.026 mmol), 1,1′-bis(diphenylphosphino)ferrocene (0.015 g, 0.026 mmol) and potassium phosphate (0.138 g, 0.654 mmol) in dioxane (8.5 ml) was stirred at 80° C. for 16 h. and then at 110° C. for 2 days. The mixture was then filtered through a pad of diatomaceous earth and the solvent was evaporated in vacuo. The residue was purified by column chromatography (silica gel; dichloromethane/methanol 70/30) to yield D11 (0.089 g, 48%) as a yellow solid. C 21 H 25 F 3 N 4 O 2 requires 422; Found 423 (MH + ).
Description 12
4-[5-(4′-Fluorobiphenyl-4-yl)-6-trifluoromethyl-pyridazin-3-yl]-piperazine-1-carboxylic acid tert-butyl ester (D12)
[0127]
[0128] A mixture of 4-[5-(4-bromophenyl)-6-trifluoromethyl-pyridazin-3-yl]-piperazine-1-carboxylic acid tert-butyl ester (0.2 g, 0.41 mmol) (prepared by procedures similar to those described for D8), 4-fluorobenzeneboronic acid (0.069 g, 0.49 mmol), trans-Pd(OAc) 2 (Cy 2 NH) 2 (0.015 g, 0.026 mmol), prepared by following the procedure described in Tao, B.; Boykin, D. W. Tetrahedron Lett. 2003, 44, 7993-7996, and potassium phosphate (0.261 g, 1.23 mmol) in dioxane (3 ml) was stirred at 80° C. overnight. The reaction mixture was then diluted with dichloromethane and extracted with a saturated solution of sodium carbonate. The organic layers were separated, dried (Na 2 SO 4 ), filtered and the solvent evaporated in vacuo. The residue was then purified by column chromatography (silica gel; dichloromethane/heptane 3:7 to 10:0). The desired fractions were collected and evaporated in vacuo to yield D12 (0.115 g, 56%). C 26 H 26 F 4 N 4 O 2 requires 502; Found 503 (MH + ).
Description 13
4-(6-Chloro-5-phenyl-pyridazin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester (D13)
[0129]
[0130] A mixture of 3,6-dichloro-4-phenyl-pyridazine (0.41 g, 1.82 mmol), prepared by following the procedure described in WO-2005/013907, N-Boc-piperazine (0.509 g, 2.73 mmol) and diisopropylethylamine (0.634 ml, 3.64 mmol) in acetonitrile (7.5 ml) was stirred at 180° C. for 40 min., under microwave irradiation, and then for a further 30 min. After this period, additional amounts of diisopropylethylamine (0.1 ml, 0.57 mmol) and N-Boc-piperazine (0.1 g, 0.54 mmol) were added and the resulting mixture was stirred at 180° C. for 40 min. The solvent was evaporated in vacuo and then, dichloromethane and a saturated solution of ammonium chloride were added. The organic layer was separated, dried (Na 2 SO 4 ), filtered and the solvent evaporated in vacuo. The residue was then purified by column chromatography (silica gel; dichloromethane and heptane/ethyl acetate 8:2 to 7:3). The desired fractions were collected and evaporated in vacuo to yield D13 (0.137 g, 20%) as a white solid. C 19 H 23 ClN 4 O 2 requires 374; Found 375 (MH + ).
Description 14
4-(6-Cyano-5-phenyl-pyridazin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester
[0131]
[0132] To a mixture of zinc cyanide (0.077 g, 0.66 mmol) and tetrakis(triphenylphosphine)palladium (0) (0.1 g, 0.09 mmol) was added a solution of 4-(6-chloro-5-phenyl-pyridazin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester (D13) (0.137 g, 0.36 mmol) in N,N-dimethylformamide (3.5 ml). The resulting mixture was stirred at 160° C. for 30 min, under microwave irradiation. The solvent was evaporated in vacuo to yield D14 (0.133 g, quant.). C 20 H 23 N 5 O 2 requires 365; Found 366 (MH + ).
Description 15
4-[5-(5-Chloro-thiophen-2-yl)-6-trifluoromethyl-pyridazin-3-yl]-piperazine-1-carboxylic acid tert-butyl ester (D15)
[0133]
[0134] A mixture of 4-(5-iodo-6-trifluoromethyl-pyridazin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester (D10) (0.20 g, 0.436 mmol), 5-chlorothiophene-2-boronic acid (0.082 g, 0.51 mmol), tetrakis(triphenylphosphine)palladium (0) (0.024 g, 0.021 mmol) and sodium carbonate (0.103 g, 0.96 mmol) in dimethoxyethane (3 ml) and water (0.75 ml) was stirred in a sealed tube at 110° C. for 16 h. The mixture was then filtered through a pad of diatomaceous earth and the solvent was evaporated in vacuo. The residue was purified by column chromatography (silica gel; dichloromethane/10% ammonia in methanol (7M) in dichloromethane 97/3) to yield D15 (0.152 g, 67%) as a yellow syrup. C 18 H 20 ClF 3 N 4 O 2 S requires 448; Found 449 (MH + ).
Example 1
4-Phenyl-6-piperazin-1-yl-3-trifluoromethyl-pyridazine (E1)
[0135]
[0136] To a solution of 4-(5-phenyl-6-trifluoromethyl-pyridazin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester (D4) (1.8 g, 0.0044 mol) in methanol (125 ml) was added Amberlyst® 15 ion exchange resin, acidic form (4.1 mmol/g) (5.3 g, 0.022 mol) and the reaction mixture was shaken at room temperature for 18 h. After this period, the mixture was filtered and then a saturated solution of ammonia in methanol was added. The mixture was shaken for 1 h, filtered and the filtrate evaporated in vacuo. The crude product was crystallised from ether/heptane to yield E1 (1.3 g, 96%). C 15 H 15 F 3 N 4 requires 308; Found 309 (MH + ).
[0137] Melting point (ether/heptane): 130.7° C.
[0138] 1 H NMR (500 MHz, chloroform-d) δ ppm: 1.71 (bs, 1H), 3.01 (t, J=5.20 Hz, 4H), 3.77 (t, J=5.20 Hz, 4H), 6.71 (s, 1H), 7.29-7.37 (m, 2H), 7.42-7.49 (m, 3H). 13 C NMR (126 MHz, chloroform-d) δ ppm: 45.72 (s, 2 CH 2 ), 45.76 (s, 2 CH 2 ), 112.73 (s, CH), 122.48 (q, J=581 Hz, C), 128.19 (s, CH), 128.36 (s, 2 CH), 129.01 (s, CH), 135.66 (s, C), 140.55 (s, C), 141.03 (s, C), 160.22 (s, C).
Example 2
6-(4-Ethylpiperazin-1-yl)-4-phenyl-3-trifluoromethyl-pyridazine (E2)
[0139]
[0140] To a mixture of 4-phenyl-6-piperazin-1-yl-3-trifluoromethyl-pyridazine (E1) (0.15 g, 0.49 mmol) in tetrahydrofuran (5 ml), was added acetaldehyde (55 ml, 0.97 mmol). The reaction mixture was stirred at room temperature for 30 min., and then sodium triacetoxyborohydride (0.154 g, 0.73 mmol) was added. The reaction mixture was stirred at room temperature for 16 h. Then, more acetaldehyde (55 ml, 0.97 mmol) and sodium triacetoxyborohydride (0.154 g, 0.73 mmol) were added and the mixture was stirred at room temperature for 4 h. Dichloromethane was then added and the mixture was extracted with a saturated solution of ammonium chloride. The organic phase was separated, dried (Na 2 SO 4 ), filtered and the solvent evaporated in vacuo. The residue was purified by column chromatography (silica gel; ethyl acetate/10% ammonia in methanol (7M) in dichloromethane 10:0 to 8:2). The desired fractions were collected, the solvent evaporated in vacuo, the residue dissolved in acetonitrile and converted into its hydrochloric acid salt by addition of a saturated solution of hydrochloric acid in diethyl ether. The white solid obtained was filtered and dried affording E2 (0.039 g, 21%). C 17 H 19 F 3 N 4 .HCl; free base requires 336; Found 337 (MH + ).
[0141] Melting point: 281.9° C.
[0142] 1 H NMR (500 MHz, DMSO-d 6 ) δ ppm: 1.28 (t, J=7.22 Hz, 3H), 2.98-3.22 (m, 4H), 3.48-3.64 (m, 4H), 4.73 (d, J=13.58 Hz, 2H), 7.32-7.46 (m, 3H), 7.46-7.60 (m, 3H), 11.26 (br. s., 1H).
Example 3
6-[4-(3,5-Difluorobenzyl)piperazin-1-yl]-4-phenyl-3-trifluoromethyl-pyridazine (E3)
[0143]
[0144] A mixture of 4-phenyl-6-piperazin-1-yl-3-trifluoromethyl-pyridazine (E1) (0.050 g, 0.16 mmol), 3,5-difluorobenzyl bromide (0.031 ml, 0.24 mmol) and diisopropylethylamine (0.056 ml, 0.32 mmol) in acetonitrile (2 ml) was stirred at 100° C. for 10 min., under microwave irradiation. The solvent was evaporated in vacuo and then, dichloromethane and ammonium chloride (10% aqueous solution) were added. The mixture was filtered through a diatomaceous earth cartridge. The solvent was then evaporated in vacuo and the residue was purified by CC-TLC (centrifugal circular thin-layer chromatography) on a chromatotron (a preparative, centrifugally accelerated, radial, thin-layer chromatograph). The crude product was crystallised from diethyl ether/heptane to yield E3 (0.037 g, 52%) as a solid. C 22 H 19 F 5 N 4 requires 434; Found 435 (MH + ).
[0145] Melting point: 138.8° C.
[0146] 1 H NMR (400 MHz, chloroform -d) δ ppm: 2.56-2.62 (m, 4H), 3.54 (s, 2H), 3.78-3.85 (m, 4H), 6.72 (tt, J=8.91, 2.28 Hz, 1H), 6.71 (s, 1H), 6.86-6.95 (m, 2H), 7.28-7.35 (m, 2H), 7.41-7.51 (m, 3H).
Example 4
cis-6-(3,5-Dimethylpiperazin-1-yl)-4-phenyl-3-trifluoromethyl-pyridazine (E4)
[0147]
[0148] A mixture of 6-chloro-4-phenyl-3-trifluoromethyl-pyridazine (D3) (0.15 g, 0.58 mmol), 2,6-cis-dimethylpiperazine (0.097 g, 0.87 mmol) and diisopropylethylamine (0.202 ml, 1.16 mmol) in acetonitrile (3 ml) was stirred at 180° C. for 30 min., under microwave irradiation. The solvent was evaporated in vacuo and then dichloromethane and a saturated solution of ammonium chloride were added. The mixture was filtered and the solvent evaporated in vacuo. The residue was purified by column chromatography (silica gel; 1-3% ammonia in methanol (7M)/dichloromethane). The desired fractions were collected and evaporated in vacuo. The product thus obtained was treated with a solution of hydrochloric acid in diethyl ether (2M) to yield the corresponding salt E4 (0.058 g, 27%; CIS) as a pale brown solid. C 17 H 19 F 3 N 4 .HCl; free base requires 336; Found 337 (MH + ).
[0149] Melting point (ether): 285.4° C.
[0150] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 1.32 (d, J=6.63 Hz, 6H), 3.08 (dd, J=13.99, 11.51 Hz, 2H), 3.30-3.41 (m, 2H), 4.76 (d, J=13.27 Hz, 2H), 7.36-7.43 (m, 3H), 7.49-7.55 (m, 3H), 9.16-9.27 (m, 1H), 9.60 (d, J=9.74 Hz, 1H).
Example 5
2-(5-Phenyl-6-trifluoromethyl-pyridazin-3-yl)-octahydro-pyrrolo[1,2-a]pyrazine (E5)
[0151]
[0152] A mixture of 6-chloro-4-phenyl-3-trifluoromethyl-pyridazine (D3) (0.10 g, 0.39 mmol), octahydro-pyrrolo[1,2-a]pyrazine, racemic mixture, (0.053 g, 0.42 mmol) and diisopropylethylamine (0.103 ml, 0.585 mmol) in acetonitrile (3 ml) was stirred at 150° C. for 30 min., under microwave irradiation. The reaction mixture was then diluted with dichloromethane (25 ml) and extracted with a saturated solution of sodium carbonate (12 ml). The organic layers were separated, dried (Na 2 SO 4 ), filtered and the solvent evaporated in vacuo. The residue was then purified by column chromatography (silica gel; 0-2.5% ammonia in methanol (7M)/dichloromethane). The desired fractions were collected and evaporated in vacuo. The residue was precipitated from acetonitrile/heptane. The product obtained was treated with a solution of hydrochloric acid in diethyl ether (2M) to yield the corresponding salt E5 (0.081 g, 54%) as a white solid. C 18 H 19 F 3 N 4 .HCl; free base requires 348; Found 349 (MH + ).
[0153] Melting point: 104.2° C.
[0154] 1 H NMR (500 MHz, DMSO-d 6 ) δ ppm: 1.71-2.25 (m, 3.5H), 2.88-3.01 (m, 0.5H), 3.06-3.19 (m, 0.5H), 3.19-3.60 (m, 4.5H), 3.65 (d, J=11.85 Hz, 0.5H), 3.83-3.98 (m, 2H), 4.26-4.37 (m, 0.5H), 4.86 (d, J=14.16 Hz, 0.5H), 5.00 (d, J=13.29 Hz, 0.5H), 7.28 (s, 0.5H), 7.37-7.46 (m, 2.5H), 7.47-7.57 (m, 3H), 11.74 (s, 0.5H), 11.87 (s, 0.5H).
Example 6
4-(4-Fluorophenyl)-6-piperazin-1-yl-3-trifluoromethyl-pyridazine (E6)
[0155]
[0156] To a solution of 4-[5-(4-fluorophenyl)-6-trifluoromethyl-pyridazin-3-yl]-piperazine-1-carboxylic acid tert-butyl ester (D8) (1.25 g, 2.93 mmol) in methanol (50 ml) was added Amberlyst® 15 ion exchange resin, acidic form (4.1 mmol/g) (3.6 g, 14.64 mmol) and the reaction mixture was shaken at room temperature for 18 h. After this period, the mixture was filtered and then a saturated solution of ammonia in methanol was added. The mixture was shaken for 1 h, filtered and the filtrate evaporated in vacuo. The crude product was purified by HPLC. The desired fractions were collected and evaporated in vacuo to yield E6 (0.507 g, 53%). C 15 H 14 F 4 N 4 requires 326; Found 327 (MH + ).
[0157] Melting point: 137.4° C.
[0158] 1 H NMR (400 MHz, Chloroform-d) δ ppm: 1.67 (br. s., 1H), 2.99-3.05 (m, 4H), 3.74-3.82 (m, 4H), 6.68 (s, 1H), 7.15 (t, J=8.71 Hz, 2H), 7.31 (dd, J=8.50, 5.39 Hz, 2H).
Example 7
6-piperazin-1-yl-4-thiophen-3-yl-3-trifluoromethyl-pyridazine (E7)
[0159]
[0160] To a solution of 4-[5-(3-thienyl)-6-trifluoromethyl-pyridazin-3-yl]-piperazine-1-carboxylic acid tert-butyl ester (0.074 g, 0.18 mmol), prepared by procedures similar to those described for D8, in methanol (5 ml) was added Amberlyst® 15 ion exchange resin, acidic form (4.1 mmol/g) (0.218 g, 0.89 mmol) and the reaction mixture was shaken at room temperature for 18 h. After this period, the mixture was filtered and then a saturated solution of ammonia in methanol was added. The mixture was shaken for 1 h, filtered and the filtrate evaporated in vacuo. The crude product was crystallized from ether/heptane to yield E7 (0.049 g, 87%). C 13 H 13 F 3 N 4 S requires 314; Found 315 (MH + ).
[0161] Melting point (ether/heptane): 244.3° C.
[0162] 1 H NMR (400 MHz, chloroform-d) δ ppm: 1.68 (br. s., 1H), 2.98-3.05 (m, 4H), 3.73-3.81 (m, 4H), 6.78 (s, 1H), 7.14-7.21 (m, 1H), 7.36-7.45 (m, 2H).
Example 8
6-piperazin-1-yl-4-o-tolyl-3-trifluoromethyl-pyridazine (E8)
[0163]
[0164] To a solution of 4-[5-(2-tolyl)-6-trifluoromethyl-pyridazin-3-yl]-piperazine-1-carboxylic acid tent-butyl ester (D11) (0.089 g, 0.21 mmol) in methanol (7 ml) was added Amberlyst® 15 ion exchange resin, acidic form (4.1 mmol/g) (0.257 g, 1.05 mmol) and the reaction mixture was shaken at room temperature for 18 h. After this period, the mixture was filtered and then a saturated solution of ammonia in methanol was added. The mixture was shaken for 1 h, filtered and the filtrate evaporated in vacuo. The residue was purified by HPLC and the desired fractions were collected and evaporated in vacuo to yield E8 (0.026 g, 50%) as a white solid. C 16 H 17 F 3 N 4 requires 322; Found 323 (MH + ).
[0165] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 2.05 (s, 3H), 2.74-2.83 (m, 4H), 3.37 (br. s., 1H), 3.62-3.72 (m, 4H), 7.15 (t, J=3.63 Hz, 2H), 7.26 (td, J=7.26, 1.66 Hz, 1H), 7.31-7.38 (m, 2H).
Example 9
4-(4′-Fluorobiphenyl-4-yl)-6-piperazin-1-yl-3-trifluoromethyl-pyridazine (E9)
[0166]
[0167] A mixture of 4-[5-(4′-fluorobiphenyl-4-yl)-6-trifluoromethyl-pyridazin-3-yl]-piperazine-1-carboxylic acid tert-butyl ester (D12) (0.115 g, 0.23 mmol) and trifluoroacetic acid (2 ml) in dichloromethane (8 ml) was stirred at room temperature for 2 h. The solvent was evaporated in vacuo and then, dichloromethane and a saturated solution of sodium carbonate were added. The organic layers were separated, dried (Na 2 SO 4 ), filtered and the solvent evaporated in vacuo. The residue was then purified by column chromatography (silica gel; 1-3% ammonia in methanol (7M)/dichloromethane). The desired fractions were collected and evaporated in vacuo to yield E9 (0.084 g, 91%). C 21 H 18 F 4 N 4 requires 402; Found 403 (MH + ).
[0168] Melting point: 161.9° C.
[0169] 1 H NMR (400 MHz, chloroform-d) δ ppm: 1.72 (br. s., 1H), 2.99-3.05 (m, 4H), 3.75-3.82 (m, 4H), 6.74 (s, 1H), 7.13-7.20 (m, 2H), 7.40 (d, J=8.29 Hz, 2H), 7.57-7.64 (m, 4H).
Example 10
4-Phenyl-6-piperazin-1-yl-pyridazine-3-carbonitrile (E 10)
[0170]
[0171] To a solution of 4-(6-cyano-5-phenyl-pyridazin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester (D14) (0.133 g, 0.37 mmol) in methanol (10 ml) was added Amberlyst® 15 ion exchange resin, acidic form (4.1 mmol/g) (1.3 g, 5.3 mmol) and the reaction mixture was shaken at room temperature for 18 h. After this period, the mixture was filtered and then a saturated solution of ammonia in methanol was added. The mixture was shaken for 1 h, filtered and the filtrate evaporated in vacuo. The residue was purified by HPLC. The desired fractions were collected and evaporated in vacuo to yield E10 (0.06989 g, 72%) as a white solid. C 15 H 15 N 5 requires 265; Found 266 (MH + ).
[0172] Melting point: 271.6° C.
[0173] 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 2.77-2.84 (m, 4H), 3.34 (br. s., 1H), 3.71-3.80 (m, 4H), 7.29 (s, 1H), 7.55-7.61 (m, 3H), 7.66-7.72 (m, 2H).
Example 27
4-(5-Chloro-thiophen-2-yl)-6-piperazin-1-yl-3-trifluoromethyl-pyridazine (E27)
[0174]
[0175] To a solution of 4-[5-(5-chloro-thiophen-2-yl)-6-trifluoromethyl-pyridazin-3-yl]-piperazine-1-carboxylic acid tert-butyl ester (D15) (0.114 g, 0.25 mmol) in methanol (10 ml) was added Amberlyst® 15 ion exchange resin, acidic form (4.1 mmol/g) (0.305 g, 1.25 mmol) and the reaction mixture was shaken at room temperature for 18 h. After this period, the mixture was filtered and then a saturated solution of ammonia in methanol was added. The mixture was shaken for 1 h, filtered and the filtrate evaporated in vacuo. The residue was then purified by column chromatography (silica gel; 3% ammonia in methanol (7M)/dichloromethane). The desired fractions were collected and evaporated in vacuo. The crude product was dissolved in a 2 M solution of hydrochoric acid in diethyl ether and the mixture stirred at room temperature for 16. The solvent was evaporated in vacuo. The solid obtained was triturated from diethyl ether to yield E27 (0.062 g, 87%). C 13 H 12 ClF 3 N 4 S requires 348; Found 349 (MH + ).
[0176] Melting point: Decomposes
[0177] 1 H NMR (500 MHz, DMSO-d 6 ) δ ppm 3.24 (br. s., 4H) 4.07 (d, J=5.2 Hz, 4H) 7.23 (d, J=3.8 Hz, 1H) 7.26 (d, J=3.8 Hz, 1H) 7.41 (s, 1H) 9.45 (br. s., 2H).
Example 40
4-Phenyl-6-piperazin-1-yl-3-trifluoromethyl-pyridazine monohydrochloride (E40)
[0178]
[0179] To a solution of E1 (16 g, 51.90 mmol) in 2-butanone (400 ml) warmed to 50° C. was added dropwise, hydrochloric acid in 2-propanol (6N, 51.90 mmol). The mixture was heated at reflux temperature for 90 minutes and then stirred for 2 hours at 50° C. and further overnight at room temperature. The precipitated crystals were filtered off and dried under vacuum at 45° C., to yield E40 (10.4 g, 58%).
[0180] Melting point: >185° C. (decomposes).
[0181] The following Examples (E11-E 19) were prepared by procedures similar to those described for Example (E6). Example (E20) was prepared by deprotection of Description (D13) according to a procedure analogous to the one reported for Example (E1). Example (E28) was prepared in analogy to (E27) but using potassium carbonate as base and 1,4-dioxane as solvent. Examples (E29) (toluene/ethanol/H 2 O), (E30) (toluene/ethanol/H 2 O), (E31) (1,4-dioxane/H 2 O), (E32) (1,4-dioxane/H 2 O), (E33) (1,4-dioxane/H 2 O), (E34) (1,4-dioxane/H 2 O) and (E35) (1,4-dioxane/H 2 O) were prepared by procedures similar to those described for Example (E27) but using the solvents specified for each case respectively. Examples (E18, E27, E28, E31, E32, E33 and E34) were isolated as hydrochloric acid salts.
[0182] The value in the column M.Wt free base, is the exact mass calculated using the exact masses of the most abundant isotopes.
[0000]
Ex.
Melting Point (° C.)
Molecular Formula
M.Wt Free base
MH+
RT (min)
LCMS Method
E1
CF 3
130.7
C 15 H 15 F 3 N 4
308
309
3.13
1
E6
CF 3
137.4
C 15 H 14 F 4 N 4
326
327
3.39
1
E7
CF 3
244.3
C 13 H 13 F 3 N 4 S
314
315
2.92
1
E8
CF 3
nd
C 16 H 17 F 3 N 4
322
323
3.37
2
E9
CF 3
161.9
C 21 H 18 F 4 N 4
402
403
4.65
1
E10
CN
271.6
C 15 H 15 N 5
265
266
2.07
1
E11
CF 3
110.6
C 16 H 17 F 3 N 4
322
323
3.67
1
E12
CF 3
198.2
C 15 H 14 ClF 3 N 4
342
343
3.74
1
E13
CF 3
nd
C 15 H 15 F 3 N 4 O
324
325
2.26
1
E14
CF 3
138.2
C 15 H 14 BrF 3 N 4
386
387
3.99
1
E15
CF 3
144.7
C 15 H 14 F 4 N 4
326
327
3.32
3
E16
CF 3
178.8
C 15 H 14 ClF 3 N 4
342
343
3.66
1
E17
CF 3
128.1
C 19 H 17 F 3 N 4
358
359
4.01
1
E18
CF 3
281.8
C 19 H 17 F 3 N 4 •HCl
358
359
3.75
1
E19
CF 3
112.6
C 13 H 13 F 3 N 4 S
314
315
2.83
1
E20
Cl
173.9
C 14 H 15 ClN 4
274
275
2.29
4
E27
CF 3
decomposes
C 13 H 12 ClF 3 N 4 S•HCl
348
349
3.55
4
E28
CF 3
decomposes
C 16 H 16 F 4 N 4 •HCl
340
341
3.39
4
E29
CF 3
101.0
C 14 H 15 F 3 N 4 S
328
329
3.07
4
E30
CF 3
98.1
C 14 H 15 F 3 N 4 S
328
329
3.30
4
E31
CF 3
287.7
C 16 H 17 F 3 N 4 O•HCl
338
339
4.39
6
E32
CF 3
198.7
C 17 H 20 F 3 N 5 •HCl
351
352
4.13
6
E33
CF 3
decomposes
C 15 H 14 F 4 N 4 •HCl
326
327
4.41
6
E34
CF 3
286.3
C 15 H 13 Cl 2 F 3 N 4 •HCl
376
377
4.83
6
E35
CF 3
199.1
C 21 H 19 F 3 N 4
384
385
4.00
7
[0183] Example (E21) was prepared by a procedure similar to the one described for (E3), examples (E22, E24 and E25) were prepared by procedures similar to those described for (E2), (E23) was prepared from (E1) by reductive amination with (1-ethoxycyclopropoxy)trimethylsilane following the procedure described in Gillaspy, M. L.; Lefker, B. A; Hada, W. A.; Hoover, D. J. Tetrahedron Letters 1995, 36, 7399-7402, E(26) was prepared by a procedure similar to the one those described for (E4) and examples (E36, E37, E38 and E39) were prepared by procedures similar to (E2) but using the hydrochloric acid salt of E1 as starting material, dichloromethane as solvent and triethyl amine, respectively. Examples (E2), (E4), (E5), (E22) and (E26) were isolated as hydrochloric acid salts. Examples (E5) and (E26) (trans) were obtained as racemic mixtures.
[0000]
Ex.
Melting Point (° C.)
Molecular Formula
M.Wt Free base
MH+
RT (min)
LCMS Method
E2
281.9
C 17 H 19 F 3 N 4 •HCl
336
337
4.23
1
E3
138.8
C 22 H 19 F 5 N 4
434
435
5.57
1
E4
285.4
C 17 H 19 F 3 N 4 •HCl
336
337
4.05
5
E5
104.2
C 18 H 19 F 3 N 4 •HCl
348
349
4.38
1
E21
185.1
C 22 H 19 F 5 N 4
434
435
5.49
1
E22
163.3
C 16 H 17 F 3 N 4 •HCl
322
323
3.95
1
E23
152.0
C 18 H 19 F 3 N 4
348
349
4.75
1
E24
129.8
C 18 H 21 F 3 N 4
350
351
4.64
4
E25
102.9
C 19 H 23 F 3 N 4
364
365
5.05
4
E26
MIXTURE OF TRANS
273.0
C 17 H 19 F 3 N 4 •HCl
336
337
3.99
5
E36
nd
C 22 H 21 F 3 N 4
398
399
3.83
7
E37
nd
C 21 H 20 F 3 N 5
399
400
4.49
6
E38
nd
C 21 H 20 F 3 N 5
399
400
4.77
6
E39
nd
C 19 H 21 F 3 N 4
362
363
4.69
6
Pharmacology
In Vitro Binding Affinity for Human D2 L Receptor
[0184] Frozen membranes of human Dopamine D2L receptor-transfected CHO cells were thawed, briefly homogenised using an Ultra-Turrax T25 homogeniser and diluted in Tris-HCl assay buffer containing NaCl, CaCl 2 , MgCl 2 , KCl (50, 120, 2, 1, and 5 mM respectively, adjusted to pH 7.7 with HCl) to an appropriate protein concentration optimised for specific and non-specific binding. Radioligand [ 3 H]Spiperone (NEN, specific activity ˜70 Ci/mmol) was diluted in assay buffer at a concentration of 2 nmol/L. Prepared radioligand (50 μl), along with 50 μl of either the 10% DMSO control, Butaclamol (10 −6 mol/l final concentration), or compound of interest, was then incubated (30 min, 37° C.) with 400 μl of the prepared membrane solution. Membrane-bound activity was filtered through a Packard Filtermate harvester onto GF/B Unifilterplates and washed with ice-cold Tris-HCl buffer (50 mM; pH 7.7; 6×0.5 ml). Filters were allowed to dry before adding scintillation fluid and counting in a Topcount scintillation counter. Percentage specific bound and competition binding curves were calculated using S-Plus software (Insightful). Most compounds had a pIC 50 value>5.0.
Fast Dissociation
[0185] Compounds showing an IC 50 less than 10 μM were tested in an indirect assay adapted from a method published by Josee E. Leysen and Walter Gommeren, Journal of Receptor Research, 1984, 4(7), 817-845, to evaluate their rate of dissociation. Compounds at a concentration of 4 times their IC 50 were first incubated for one hour with human D2L receptor cell membranes in a volume of 2 ml at 25° C., then filtered over glass-fibre filter under suction using a 40 well multividor. Immediately after, the vacuum was released. 0.4 ml of pre-warmed buffer (25° C.) containing 1 nM [ 3 H]spiperone was added on the filter for 5 minutes. The incubation was stopped by initiating the vacuum and immediate rinsing with 2×5 ml of ice-cold buffer. The filter-bound radioactivity was measured in a liquid scintillation spectrometer. The principle of the assay is based on the assumption that the faster a compound dissociates from the D2 receptor, the faster [ 3 H]spiperone binds to the D2 receptor. For example, when D2 receptors are incubated with clozapine at the concentration of 1850 nM (4×IC 50 ), [ 3 H]spiperone binding is equivalent to 60-70% of its total binding capacity (measured in absence of drug) after 5 min incubation on filter. When incubated with other antipsychotics, [ 3 H]spiperone binding varies between 20 and 50%. Since clozapine was included in each filtration run, tested compounds were considered fast dissociating D2 antagonists if they were dissociating as fast or faster than clozapine. Most tested compounds had a dissociation rate faster than that of clozapine, i.e. >50%.
In Vitro Binding Affinity for Human D3 Receptor
[0186] Frozen membranes of human Dopamine D3 receptor-transfected CHO cells were thawed, briefly homogenized using an Ultra-Turrax T25 homogeniser and diluted in 50 mM Tris-HCl assay buffer containing 120 mM NaCl, 2 mM CaCl 2 , 1 mM MgCl 2 , 5 mM KCl and 0.1% BSA (adjusted to pH 7.4 with HCl) to an appropriate protein concentration optimized for specific and non-specific binding. Radioligand [ 125 I]Iodosulpride (Amersham, specific activity ˜2000 Ci/mmol) was diluted in assay buffer at a concentration of 2 nM. Prepared radioligand (20 μl), along with 40 μl of either the 10% DMSO control, Risperidone (10 −6 M final concentration), or compound of interest, was then incubated with 70 μl of the prepared membrane solution and 70 μl of WGA coated PVT beads (0.25 mg/well final concentration). After shaking for 24 hours at RT plates were counted in a Topcount™ scintillation counter. Percentage specific binding and competition binding curves were calculated using S-Plus software (Insightful).
In Vitro Binding Affinity for Human 5HT6 Receptor
[0187] Frozen membranes of human Serotonin 5HT6 receptor-transfected HEK cells were thawed, briefly homogenized using an Ultra-Turrax T25 homogeniser and diluted in 50 mM Tris-HCl assay buffer containing 10 mM MgCl 2 , 1 mM EDTA and 10 μM Pargyline (adjusted to pH 7.4 with HCl) to an appropriate protein concentration optimized for specific and non-specific binding. Radioligand [ 3 H]Lysergic acid diethylamide (Perkin Elmer, specific activity ˜80 Ci/mmol) was diluted in assay buffer at a concentration of 20 nM. Radioligand (20 μl), along with 40 μl of either the 10% DMSO control, Methiothepine (10 −5 M final concentration), or compound of interest, was then incubated with 70 μl of the prepared membrane solution and 70 μl of WGA coated PVT beads (0.25 mg/well final concentration). After shaking for 24 hours at RT plates were counted in a Topcount™ scintillation counter. Percentage specific binding and competition binding curves were calculated using S-Plus software (Insightful).
[0000]
D2 L binding
5-HT6 binding
D3 binding
Ex.
pIC 50
D2 dissociation
pIC 50
pIC 50
E20
5.85
n.d.
5.36
6.82
E21
5.70
n.d.
>5
5.83
E1
5.96
75%
6.23
7.18
E3
6.21
n.d.
>5
<5
E6
6.43
55%
6.67
7.44
E13
5.29
n.d.
5.45
<5
E4
5.42
n.d.
5.07
<5
E26
5.22
n.d.
5.64
<5
E14
5.39
n.d.
5.37
<5
E11
5.90
n.d.
6.13
7.05
E7
6.06
81%
5.81
<5
E10
5.25
86%
5.34
<5
E15
5.24
n.d.
5.81
6.2
E22
6.11
79%
5.90
7.41
E2
6.69
80.5%
5.50
7.60
E12
5.44
n.d.
5.76
6.46
E23
5.73
n.d.
<5
6.56
E16
5.32
n.d.
6.61
6.26
E17
5.10
n.d.
6.36
6.40
E19
5.86
n.d.
5.71
6.83
E18
5.11
n.d.
6.80
<5
E8
6.00
78.5%
6.58
<5
E9
6.10
48%
5.74
7.32
E5
5.90
84%
5.99
<5
E25
7.16
47%
5.57
8.58
E24
7.17
n.d.
5.27
<5
E27
5.82
n.d.
6.10
<5
E28
6.43
n.d.
6.61
7.32
E29
5.45
n.d.
6.27
<5
E30
6.12
82%
6.25
7.27
E36
7.48
n.d.
5.18
<5
E37
6.25
n.d.
<5
6.75
E38
6.55
n.d.
<5
7.06
E39
7.22
n.d.
5.41
<5
E31
<5
n.d.
5.95
6.32
E32
<5
n.d.
6.01
5.89
E33
5.91
n.d.
5.89
7.28
E34
5.33
n.d.
6.10
7.06
E35
5.57
n.d.
5.82
6.97
n.d.: not determined | The present invention relates to 4-aryl-6-piperazin-1-yl-3-substituted-pyridazines that are fast dissociating dopamine 2 receptor antagonists, processes for preparing these compounds, pharmaceutical compositions comprising these compounds as an active ingredient. The compounds find utility as medicines for treating or preventing central nervous system disorders, for example schizophrenia, by exerting an antipsychotic effect without motor side effects. | 2 |
FIELD OF THE INVENTION
[0001] The invention relates to fine particles, to an apparatus for use in this process, and to a process for preparing fine particles. In particular, the invention relates to fine particles comprising a core and coating, and to a process and apparatus for preparing these.
BACKGROUND OF THE INVENTION
[0002] A common problem in the preparation of fine particles is their tendency to agglomerate, this is generally believed to be as a result of their high surface area to volume ratio which causes the particles to have a relatively high surface energy. It has been speculated that the agglomeration could be as a result of electrostatic forces between the particles, cold sintering, or van der Waals interactions. The result of this agglomeration is that fine particles are generally found as clusters, platelets or strings of the fine particles, and not as isolated fine particulate matter.
[0003] It would be advantageous to provide fine particles which are not agglomerated as agglomeration reduces the surface area of a given mass of fine particles. This would provide systems where either less fine particulate matter would be required for use in surface chemistry applications, or the same mass of fine particles could be used, but faster reaction rates observed as a result of the larger surface area available for reaction or physical absorption. The above properties are of particular importance where the fine particles are being used as catalysts as it is the surface chemistry of the particles, and hence their surface energy, which promotes the reactions.
[0004] Further, un-agglomerated fine particles will disperse more efficiently in liquids, the resulting colloids having the properties of a “solution” of the fine particle, as though the particles were not merely suspended in the liquid, but dissolved therein. The ability to form such colloids enhances the ease and speed of reactions using the fine particles; as the particles can be intimately mixed with the reactants in solution. With agglomerated fine particles it is generally necessary to sonicate a suspension of the agglomerated fine particles, and often to add a dispersant, in order to produce a stable colloid. This places limitations upon the presentation of the fine particles to any medium with which they are to interact. As a result, the formation of liquid suspensions in this way can result in fine particles with altered surfaces, and reduced surface energy, making them less suitable for their intended application. As noted above, dispersants such as surfactants can be used to stabilise the suspensions, or to help the fine particles form coatings. The use of dispersants is undesirable as not only does their use increase the cost of the product, but the dispersant also acts to reduce the surface energy of the fine particles, retarding, reducing or degrading their utility in surface chemistry applications.
[0005] Where the particles are sintered, even sonication will be unlikely to separate the fine particles. The energy provided by ultrasound would be insufficient to break the bonds. Without being bound by theory, it is thought that sintering occurs just after fine particle formation, as a result of the high temperatures at which the particles are formed in plasma processes. Further sintering may be observed as the particles cool, even at or near ambient temperature due to the high surface energy of the fine particles before they are contaminated (for instance with air). It has been postulated that fine particles formed from a gaseous or plasma state may even form bonds or links as the particles are produced.
[0006] Another advantage of producing unagglomerated fine particles would be their ability to pass through fine membranes and filters in the same manner as many large molecules. For instance, it could be of use to produce a colloid of fine particles in which the fine particles can pass across a permeable membrane under osmotic pressure.
[0007] It would therefore be desirable to provide fine particles which do not significantly agglomerate or sinter and which are stable in their pure form, with substantially all of their surface energy intact. The fine particles of the invention and the process and apparatus for preparing these are intended to ameliorate one or more of the above problems.
SUMMARY OF INVENTION
[0008] In accordance with a first aspect of the invention there is therefore provided a fine particle comprising a core and a coating, wherein the coating comprises organic molecules. By fine particles is meant particles having a size of or less than a micron and generally in the order of 100 μm or less. Preferably the fine particles are nanoparticles, by nanoparticles is meant particles having nanometric dimensions, and nanoparticles may have, for example, dimensions in the order of a few nanometres to several hundred nanometres. Nanoparticles may be spherical or aspherical, and may also be known as a nanopowder or as a nanometric material. Advantageously, the fine particles lie in the size range 1 to 200 nm, more preferably in the range 5 to 100 nm and more preferably in the range 10 to 50 nm, often in the range 10 to 20 nm.
[0009] In some embodiments the fine particle of the invention is free from any internal contamination by sulphur, nitrogen, chlorine, carbon or hydrogen. By “internal contamination” is meant that the core does not contain any contaminants of this type. In some embodiments the core of the fine particle of the invention will be substantially free from contamination by substrates including contaminants selected from sulphur, nitrogen, chlorine, carbon, hydrogen and combinations thereof. In other embodiments the contaminants will be selected from sulphur, nitrogen, chlorine, carbon, hydrogen, fluorine, oxygen, acetates, formates, organic salts and combinations thereof. It is an advantage of the thermal plasma process of the invention that the core is pure when compared to prior art fine particles.
[0010] Known (wet chemistry) techniques for the preparation of fine particles give rise to cores containing low levels of contaminants, particularly where the core is metal containing and the chemical routes to prepare the fine particles employ metal salts. Accordingly, using the process of the invention it is possible to produce fine particles which are substantially free from such internal contamination.
[0011] By “substantially free” is meant that the fine particles of the invention contain in the range 0 to 100 ppb, often 0 to 50 ppb, in many examples 0 to 10 ppb, often 0 to 5 ppb of contaminant. Typically the contaminants will be selected from those listed above. It will generally be the case that the surface of the particle has a higher level of contaminants than the core of the particle, as particles which have been made by processes in accordance with the invention will be coated last by elements and compounds of lower boiling point as these condense after materials with higher boiling points.
[0012] Often the fine particle will comprise in the core and/or the coating a noble gas residue, often argon or helium. The noble gas residue will often be found in the core and results from inclusion in the structure of the fine particle samples of the carrier gas used in the plasma. Often in a sample of particles prepared the process of the invention, approximately 20 to 50% of particles will contain a noble gas residue.
[0013] In some examples the fine particle will be spherical. The fine particles of the invention, when made using a thermal plasma process such as that described in this application, are spherical to within the limits of detection. For instance, under SEM/TEM analysis the particles appear spherical. Without being bound by theory this is believed to be due to the enormous force exerted by the surface tension of the molten core material which, because of the tiny dimensions involved, have a very high surface to volume ratio. Accordingly, when compared to fine particles prepared using wet chemistry routes, the fine particles of the invention are of a more regular shape because they do not undergo the chemical wetting which occurs in wet chemistry synthetic routes and which reduces the surface energy of fine particles prepared using wet chemistry. In wet chemistry, chemical wetting reduces the thermodynamic driving force and so low energy surfaces (for instance partially flat surfaces) will form more easily as the surface tension is less of a factor in the determination of the shape of the particle. Further, the fine particles observed with wet chemistry techniques tend to be clusters of the first few molecules formed, rather than (as is the case with thermal plasma techniques) the fine particles cooling from a totally molten sphere.
[0014] In some embodiments it is desirable that the fine particle of the invention be one of a population of fine particles in which in the range 5 to 100%, often 10 to 75%, in some examples 25 to 50% of the fine particles demonstrate “crystal twinning” in their internal structure. By “crystal twinning” is meant that where there are dividing plains in the crystal structure of the core material of the fine particle, because the crystal structure has formed in two different directions in one sphere, the crystals are formed back-to-back. Such crystalline twinning effects occur because of the rapid speed of formation of the particles of core material in thermal plasma systems. Such structures would not be observed with wet chemistry fine particles as the high energy giving rise the crystal structures arises from the rapid speed of cooling and formation of the particles of core material occurring when thermal plasma techniques are used.
[0015] Alternatively, the fine particles may show signs of internal lattice defects of relatively high energy. High energy defects would also be absent in fine particles formed using a wet chemistry route as these particles form more slowly. It is the rapid condensation observed using thermal plasma processes as described herein which gives rise to the lattice defects. These could be observed using, for instance a high powered TEM.
[0016] In some examples the coating of the fine particle is attached exclusively to the particle itself without the presence or interference of any third element or compound. Accordingly, the fine particles of the invention may be exceptionally pure and this may arise where thermal plasma processes such as that of the invention are used to prepare the fine particles. This is because the particles are being prepared using a physical technique as opposed to a chemical technique and hence the number of contaminants present in the system is significantly reduced. Fine particles made using wet chemistry techniques, often include residues of the reagents and solvents used in their formation. Thermal plasma techniques use gaseous carriers instead of solvents.
[0017] It is desirable that the coating prevents agglomeration of each fine particle with other fine particles, the fine particles of the invention preferably need no separate stabilisation to prevent agglomeration or to stabilise any dispersion including the fine particles. The coating may also act as a gas barrier, retarding or preventing oxidation of the core. It has been found with elemental cores, such as metal cores, that the presence of the coating reduces the rate of oxidation to below 10%, possibly below 5% of that observed where the coating is absent. The coating may temporarily reduce surface energy by reducing the driving force for the surface to react with air and the like. Polar oxygen ions or oxygen may be, for example, kept at a distance by the polar coating.
[0018] In many examples of the invention, the fine particles will comprise a surface which is of single polarity. This uniformity of polarity causes the fine particles to repel one another by electrostatic repulsion, and in some examples also by steric hindrance, as a result agglomeration is prevented.
[0019] The core is preferably produced from a high surface energy material, this may be an element or a compound. Often the element will be a metal or metalloid, and the compound a metal oxide. By metalloid is meant a chemical element which is intermediate in properties between metals and non-metals, including boron, silicon, germanium, arsenic, antimony and tellurium. Where the core is a metal, it will most often be a transition metal or an alloy of a transition metal. The transition metal will often be selected from iron, nickel, copper, zinc, palladium, silver, cadmium, gold and alloys thereof. In some embodiments, the transition metal will comprise copper, often the transition metal will be copper alone. Aluminium, or aluminium oxide may also be used.
[0020] Historically a “clean” fine particulate copper has been very difficult to achieve, and almost impossible to achieve in a reliable, repeatable manner. The subject invention may have overcome this problem. Fine particulate copper, has applications in the printed electronics industry, where ink jet printing of a fine particle dispersion of the copper could be used by the printed electronics industry to prepare circuits. The fine particulate copper of the invention could be used in this way, optionally with some post-printing treatment to modify the copper conductivity.
[0021] Some prior art uses inks of fine particles for use in conducting circuits by different processes to the invention, which have high resistance and excessive temperatures to sinter them.
[0022] Whilst the coating may be partial, the coating is most effective in preventing agglomeration and/or oxidation where it substantially covers the core. In preferred examples the surface of the core is completely covered by the coating. The coating material is desirably a material which forms only low energy reversible bonds with the core. This provides for removal of the coating prior to use of the fine particles. Organic compounds have been found to work in this way, and hence these are generally used in the invention.
[0023] In many instances the organic molecules will comprise polar (or even charged) molecules. Polar organic molecules are often used as these easily form monolayers. It is particularly useful if the polar molecule is elongate, and the functional group conferring the polarity is at one end of the molecule (such as a long chain carboxylic acid or a straight chain thiol). Molecules of this structure form efficient monolayers. For the purposes of this invention the monolayer is preferably uniform in that all of the molecules are aligned with the overall positively charged ends (whether these are fully charge carrying or whether there is only a partial positive or negative charge as a result of the electronic properties of the atoms in the molecule) together on either the outer surface of the fine particle or the inner surface. Whether the positive or negative charge is on the outer surface of the fine particle will depend upon the nature of the core material. The coating therefore works to prevent agglomeration through the electrostatic repulsion of like charges on the surface of the fine particles.
[0024] A wide variety of organic molecules may be used, including surfactants. It is important to note that where surfactants are used, these are as a coating and not as a dispersant as has historically been their application in nanoparticle systems. As the skilled reader will be aware, surfactants are generally elongate organic molecules and are often charged, surfactants are therefore appropriate for use in forming the coatings of the invention for the reasons outlined above.
[0025] The polar molecules may be carboxylic acids, sulfates, alcohols, nitrates, phosphates, amines, amides, thiols and combinations thereof. In many examples the polar molecules will comprise a carboxylic acid, an amine, an amide, a thiol or a combination thereof. Where carboxylic acids are used, these will often be selected from stearic acid, oleic acid, lauric acid, myristic acid, palmitic acid, caprylic acid, linoleic acid or combinations thereof.
[0026] These carboxylic acids are generally preferred as they are non-toxic, of low boiling point which makes them easy to vaporise in thermal plasmas systems, and they produce weak bonding with metals. It is this weak bonding which provides for easy removal of the acid coating to expose the high surface energy surface of the core or easy substitution for alternative ligands where the core can usefully be functionalised for specific applications. These applications include the deposition of a coating or track which can be post-treated to make it connected and to improve conductivity; or as the catalyst in a cars catalytic converter where the heat of the exhaust acts to remove the coating and expose the reactive catalytic surface below. Of the carboxylic acids tested, oleic acid has been found to be particularly appropriate for use in the fine particles of the invention.
[0027] Thiols may also be used, in particular straight chain thiols such as the C 10 -C 18 thiols. Polymeric compounds may also be used, in particular polymers with polar side chains such as PVP (polyvinylpyrrolidone). It has been found that PVP coatings are also particularly advantageous for use with the invention. The PVP adheres to the core material by co-ordination of the nitrogen and oxygen moieties.
[0028] The coating may substantially be a monolayer, a monolayer with areas of bilayer and/or trilayer or of multiple layers. By “layer” is meant a distinct area of coating one molecule thick, in a monolayer the molecules may be aligned substantially parallel to the surface of the core, or perpendicular, or at an angle in between. It will often be the case that the layer will be formed of molecules aligned substantially perpendicular to the surface of the core, such layers are often said to be of “forest” construction. It will generally be the case that the coating will be substantially monomolecular, the use of monolayer coatings reduces the amount of coating material required, provides minimal addition to the size of the fine particle, and ensures that the coating is relatively easy to remove.
[0029] The average thickness of the coating is likely to be in the region of 100-200 nm per layer, often the thickness of the coating layer will be in the region of 125-175 nm where there is a monolayer and 250-350 nm where the coating is a bilayer.
[0030] The fine particles may be dispersed in solution, and accordingly a second aspect of the invention relates to a colloidal dispersion comprising a dispersed phase and a continuous phase, wherein the dispersed phase comprises a multiplicity of fine particles according to the first aspect of the invention. The dispersions of the invention have been found to be stable at ambient temperature (in the range 20-25° C.) without the presence of dispersants for up to six-months at concentrations in the range 0.001-20 wt %, often in the range 0.01-5 wt %, in some examples in the range 0.5-2.0 wt % or 0.5-1.0 wt %.
[0031] The continuous phase may be any fluid in which the fine particles are insoluble, the fluid will typically be a liquid at ambient temperature and the liquid will typically be non-toxic, and of low boiling point, such as boiling point less than 100° C. The fluid will often be an organic solvent or water. Often the continuous phase will be ethyl acetate although isopropanol, and acetone are also sometimes used.
[0032] In accordance with a third aspect of the invention there is provided a process for the formation of fine particles comprising a core and a coating, wherein the coating comprises organic molecules; the process comprising: introducing a core material into a plasma stream thereby vaporising some or all of the core material; cooling the core material downstream from where the core material was introduced, thereby creating particles of the core material; coating particles of the core material with organic molecules in an injection zone; wherein the injection zone is downstream of a region where the particles of core material are formed. This process provides fine particles each comprising a core and a coating.
[0033] In a fourth aspect of the invention, there is provided a process for the formation of fine particles comprising a core and a coating, the process comprising:
introducing a core material into a plasma stream thereby vaporising some or all of the core material; cooling the core material downstream from where the core material was introduced, thereby creating particles of the core material; coating particles of the core material with organic molecules in a coating chamber by applying a liquid or vapour coating material or a solution of coating material to the core material; wherein the coating chamber is downstream of a region where the particles of core material are formed.
[0038] The coating material may be liquid coating material.
[0039] Thermal plasma processes have a further distinct advantage over wet chemistry techniques for preparing fine particles as thermal plasma techniques can be easily scaled up for volume production.
[0040] As noted above, fine particles have a high surface energy and hence have a tendency to agglomerate. This is problematic when the fine particles have been prepared in a thermal plasma system as the high purity and hence high surface energy of the resulting particles can result in agglomeration at far lower temperatures than would be possible for bulk products. This can even result in sintering of the particles prior to quenching which causes problems with particle filtration and adhesion of particles to the apparatus (for instance the plasma chamber and exit pipe work). This is exacerbated as the clean surfaces of the fine particles directly after formation (i.e. before exposure to air begins the oxidation process) exhibit an increased tendency to bond, even at low temperatures. For this reason, fine particle production using thermal plasma processes has historically resulted in low product yields at the downstream filter (typically the product collection stage).
[0041] Without being bound by theory, it is believed that the high surface energy is as a result of the high surface to volume ratio of the fine particles and the fine particles of the invention have cores which retain this high energy, but which are protected from surface oxidation, agglomeration and sintering by the coating. It will be obvious to one skilled in the art that the thermodynamics of this large and highly reactive surface area represents a huge driving force that will release much energy when such fine particles agglomerate or coalesce.
[0042] In embodiments of the invention where the core material is coated using a liquid coating material in order to provide un-agglomerated coated particles, the liquid coating material may be a material which is in liquid form at the coating temperature, or a solution containing dissolved coating material. As used herein, the terms “liquid” and “solution” are to be given their ordinary meaning in the art. When being described in general terms, the liquid coating material and the solution of coating material will be referred to as a “liquid medium”.
[0043] This method has the advantage of removing the possibility that coated particles may be gathered on the filter; instead these are collected from the liquid medium, separate from the collection point for uncoated particles. In addition, solution coating of the core material can provide for a greater control of the coating temperature and coating medium than “in-flight” methods where there is a risk that the coating material can be degraded if fed into a zone of the plasma flow-line which is too hot.
[0044] The core material is preferably added to the plasma stream in particulate form, even nanoparticulate form. The smaller the particles of core material are before plasma treatment, the smaller the resulting fine particles will be, and the smaller the distribution in particle size will be. The particles of core material may be produced using a variety of methods. Examples are ball-milling, deposition from a sol-gel or plasma deposition. Preferably, the particles are produced by a thermal plasma-based method and more preferably by a plasma-spray method. Plasma techniques are preferred because they are particularly suitable for forming nanoparticles having the desired physical properties.
[0045] The thermal plasma torch operates at a temperature in the range 5000° K-15,000° K. These temperatures are too high for coating the fine particles of core material as the coating material (if it did not decompose or burn) would form a compound with the core material. Therefore, the coating must occur downstream of the plasma torch, in a cooler region of the apparatus. As the coating material is injected into the apparatus in some embodiments, this region is known as the injection zone. The injection zone is typically cooled, any known cooling method may be used; however, in this invention cooling is often using a water jacket.
[0046] In embodiments of the invention where the coating material is injected into the apparatus, it is generally preferred that the coating step occurs in a part of the injection zone which is at a temperature slightly below the temperature where the coating material would decompose or pyrolyse. However, it is desirable that the coating material is injected into the injection zone at the closest point of proximity within the plasma stream to the point of formation of the particles of core material. This is the point where the temperature of the injection zone has fallen just below the decomposition/pyrolysis point of the coating material, any closer and the temperature would cause breakdown of the coating material, and coating would not occur. This may be where the temperature is 10° C. below the decomposition/pyrolysis point, often 5° C., 4° C., 3° C., 2° C., 1° C., 0.5° C., below the decomposition/pyrolysis point. It is preferred that the temperature is as high as possible as this allows the newly formed particles of core material to be coated as quickly as possible after formation. The sooner the fine particles of core material are coated, the less time there is for agglomeration/sintering of the particles to occur. The temperature of injection may be in the region 400° C.-700° C., in this temperature range many organic molecules are vaporised, but stable to the temperature applied. It is preferred that injection occur above at a temperature above the boiling point of the coating material.
[0047] Where possible, the particles of core material should be coated almost immediately on formation, often within 1 second, generally within 0.5 seconds, if possible within 0.1 seconds, 50 milliseconds, 10 milliseconds or 5 milliseconds of formation of the particles of core material.
[0048] Often the coating material will be carried into the apparatus in a gas stream, the gas acts as a carrier for the coating material allowing it to be contacted with the particles of core material in aerosol or vaporised form. The finer the spray of coating material, the more efficient and controllable the coating process and accordingly it is preferred that the coating material be carried either as a fine aerosol or in vaporised form. Vaporised form is preferred as interaction between different molecules of the coating material is at its minimum in this form.
[0049] It will be preferred for safety reasons that the gas is an inert gas such as a noble gas or nitrogen. Often argon will be used as the carrier gas because of its ready availability.
[0050] In many embodiments the inert gas stream is sprayed upwards towards the plasma torch, but does not contact the plasma torch. This is achieved by positioning the gas streams to bring the coating material into contact with the fine particles of core material at the highest possible temperature and as soon as possible after formation of the particles of core material.
[0051] In some examples the coating material is heated prior to injection. Heating the coating material reduces viscosity facilitating conversion into a fine spray.
[0052] Subsequent to coating the fine particles are recovered using organic solvents which are then evaporated from the particles. The resulting product is a free-flowing powder of fine particles of the invention. Alternatively, the removal of the organic solvent may be after the coating of a surface with the fine particles, in such examples solvent removal leaves a layer of fine particles on the surface. These may then be used, for instance, as a heterogeneous catalyst. The removal of the solvent will often be in a controlled atmosphere to prevent contamination of the surface.
[0053] In the fourth aspect of the invention, coating is achieved by coating the particles in a liquid medium. Coating in a liquid provides a practical temperature limit at which coating can occur (the boiling point of the medium), provides substantially completely un-agglomerated particles, and easy retrieval of the particles after formation.
[0054] The medium may comprise a variety of components; however, in one embodiment it will be a solution that will comprise a coating material and a solvent. In a second embodiment the medium will consist of a liquid coating, preferably without any dissolved solids, which itself may be one chemical or a mixture of chemicals to give optimal performance, including protection at a later stage from exposure to reactive gases including air, and facilitating removal of the coating when required. For this reason therefore the liquid medium may comprise a mixture of different chemicals, which may each be in solution or a liquid form (often a substantially pure liquid form) of a compound. Often the liquid comprises an organic chemical without any dissolved solids, often the liquid is “neat”.
[0055] In some examples the liquid medium comprises more than one different liquid component without any dissolved solids, the liquid or combination of liquids may be substantially free of solvent (by which we mean less than 0.1% solvent). In some examples, the liquid medium comprises a combination of one or more liquids and a solution of one or more organic solids.
[0056] Where the liquid medium is a solution, the coating material will often be present in the range 0.5-10 w/w, often 3-7 w/w, in some cases around 5 w/w. The solution may be heated, to improve solubility, to reduce the time delay required between formation of the nanoparticles and the coating step and/or to reduce the cooling effect on the gas stream. Temperatures in the range 50-90° C. may be used, often 50-70° C., in some cases a temperature of around 60° C. (so in the range 55-65° C.) may be used.
[0057] In many examples, the solvent will be selected from water, water miscible solvents, and organic solvents. Often the solvent will be selected from water, alcohols, aromatic hydrophobic solvents and combinations thereof, in some examples the solvent is selected from water, ethanol, iso-propanol, toluene and combinations thereof. In some examples the solvent will be selected from water, ethanol, dichloromethane, hexane, cyclohexane, dimethylformamide or combinations thereof.
[0058] The liquid medium will be housed in the coating chamber. In this chamber, particles of the core material are carried to the solution in a gas stream and bubbled through the medium. It will be preferred for safety reasons that the gas is an inert gas such as a noble gas or nitrogen. Often argon will be used as the carrier gas because of its ready availability.
[0059] The bubbling of the gas stream containing the particles of core material is often facilitated by designing the coating chamber as a “liquid trap” such as would be known to the person skilled in the art. In such traps the carrier gas is released into the liquid medium below the surface of the liquid, and bubbles up through the coating solution or liquid coating material to be released at the surface. During the transit of the carrier gas through the liquid medium, the particles of core material are believed to be released from the gas, coated, and retained in the liquid medium. It can be useful to ensure that the gas is at a pressure above atmospheric pressure at the point of entry to the coating chamber, in this way the bubbling process can be facilitated. Optionally, a pump may also be present at a point beyond the coating chamber to draw the carrier gas which has passed through the liquid medium from the coating chamber, by reducing the atmospheric pressure above the surface of the liquid medium.
[0060] In many embodiments the particles of core material pass from the expansion chamber where they are formed, directly to the coating chamber where they are coated during the process of bubbling the particles through the liquid coating medium. Upon coating, the coated fine particles are retained in the liquid medium and the gas forming the gas stream recovered for reuse. Typically the recovered gas will be dried prior to reuse.
[0061] The particles coated in this way are substantially completely un-agglomerated by virtue of the coating providing a barrier which prevents sintering of the core material.
[0062] The particles may be recovered from the liquid medium using any conventional means such as filtration, solvent evaporation, magnetic separation centrifugation etc. as appropriate The resulting product is a free-flowing powder of fine particles.
[0063] In a fifth aspect of the invention, the process of the third aspect of the invention is carried out using an apparatus for the formation of fine particles comprising a core and a coating; the apparatus comprising a plasma stream with an injection zone between a plasma torch and a quenching zone; wherein a coating material is injected into a stream of particles passing through the injection zone from the plasma torch to the quenching zone.
[0064] In a sixth aspect of the invention, there is provided an apparatus for the formation of fine particles comprising a core and a coating; the apparatus comprising a plasma stream with a coating chamber downstream of the plasma stream; wherein a liquid or vapour medium of coating material is housed in the coating chamber and a gas or liquid stream containing particles of a core material is fed into the coating chamber.
[0065] A liquid medium of coating material may be used. A gas stream may contain particles of the core material.
[0066] The apparatus used in the invention is a combination of a commercially available and standard system for spraying materials using a plasma, with a water-cooled and atmosphere controlled system. The object of this combination is that it allows conversion of feedstock into nanosize material, using a low cost torch and allows use of an advanced power and control system that are widely available.
[0067] In the apparatus there is provided an assembly for attachment to a plasma torch for use in the conversion of material into nanoparticles, the assembly may comprise in some examples: a plasma torch section comprising a plasma torch; an inlet channel; and a feedstock injector, positioned to direct the feedstock into the inlet channel whereby in use the feedstock injector injects the feedstock into a plasma stream from the plasma torch; an expansion chamber; a further chamber downstream of the expansion chamber defining an injection zone, the injection zone optionally being connected via a coating injection point to a fluidising apparatus via an atomiser. Further chambers to cool and collect the particles may also be present.
[0068] It is often preferred that the coating material is fluid at a point of injection, often the coating material has been vaporised. In many embodiments, the coating material is at a temperature below but close to the temperature at which the coating material decomposes/pyrolyses at the point of injection.
[0069] It is useful if the injection zone comprises a plurality of injection points. This facilitates the introduction of the coating material from different points around the plasma stream. Further, as different coating materials will have different decomposition points, it is useful if the injection points are distributed along the length of the injection zone. This allows different coating materials to be injected at different temperatures.
[0070] In other examples, in the apparatus there is provided an assembly for attachment to a plasma torch for use in the conversion of material into nanoparticles, which may comprise: a plasma torch section comprising a plasma torch; an inlet channel; and a feedstock injector, positioned to direct the feedstock into the inlet channel whereby in use the feedstock injector injects the feedstock into a plasma stream from the plasma torch; an expansion chamber; a coating chamber downstream of the expansion chamber. Further chambers to cool and collect the particles and chambers to collect the gas forming the gas stream may also be present.
[0071] As described above, the injection of the coating material may be in an inert gas stream; it is preferred that the inert gas stream does not contact the plasma torch as the coating material carried therein would decompose or burn.
[0072] The fine particles of the invention have a wide variety of applications including but not limited to applications in catalysis, water filtration and biocides. The biocidal applications would primarily be the use of the inventive fine particles as antiviral agents, possibly as coatings on or components of hard surfaces. Further, the fine particles of the invention are sufficiently stable in solution that they can be printed using ink jet technology, providing applications in fields such as printed electronics.
[0073] The invention provides a composition for inkjet use comprising particles according to the invention. Use of the fine particles according to the invention in inkjet printing and technology is also provided.
[0074] It will be clear to the skilled reader that, unless otherwise stated, all parameters appearing in this application are to be taken as modified by the word ‘about’. Additionally, unless otherwise stated each feature described in the application may be taken in combination with any other feature described in the application.
BRIEF DESCRIPTION OF THE DRAWINGS
[0075] Embodiments of the invention will now be described in detail by way of non-limiting example only with reference to the accompanying drawings in which:—
[0076] FIG. 1 is schematic diagram of the apparatus of the invention;
[0077] FIG. 2 is a is a side elevation of an embodiment of the apparatus attached to a known plasma torch;
[0078] FIG. 3 is a schematic side elevation of an injection zone;
[0079] FIG. 4 is a side elevation of a pressurising and heating unit for the coating material;
[0080] FIG. 5 is a schematic side elevation of a coating material atomiser;
[0081] FIG. 6 is a SEM image of fine copper particles with an oleic acid coating (180K);
[0082] FIG. 7 is a STEM image of fine copper particles with an oleic acid coating (200K);
[0083] FIG. 8 is a STEM image of fine copper particles with an oleic acid coating (250K);
[0084] FIG. 9 is a backscattering image of the fine copper particles of FIG. 8 ;
[0085] FIG. 10 is a STEM image of fine copper particles with an oleic acid coating (800K);
[0086] FIG. 11 is a SEM image of uncoated fine copper particles (200K);
[0087] FIG. 12 is an STEM image of uncoated fine copper particles (200K);
[0088] FIG. 13 is an XRD image of uncoated fine copper particles;
[0089] FIG. 14 is an XRD of fine copper particles with an oleic acid coating taken just after preparation of the particles and again after 30 days; and
[0090] FIG. 15 is an XRD of fine copper particles with a PVP coating taken just after preparation of the particles and again after 30 days.
[0091] FIG. 16 is schematic diagram of the apparatus of the invention;
[0092] FIG. 17 is a schematic side elevation of a coating chamber;
[0093] FIG. 18 is an XRD of copper nanoparticles coated in oleic acid using the process of the invention;
[0094] FIG. 19 is an XRD of uncoated copper nanoparticles sampled directly after nanoparticle synthesis;
[0095] FIG. 20 is an XRD of uncoated copper nanoparticles sampled after being exposed to air for 24 hours after nanoparticle synthesis;
[0096] FIG. 21 is an SEM image of the coated copper nanoparticles of FIG. 18 observed at 100K;
[0097] FIG. 22 is an STEM image of the coated copper nanoparticles of FIG. 18 observed at 200K; and
[0098] FIG. 23 is an STEM image of uncoated copper nanoparticles observed at 200K.
DETAILED DESCRIPTION OF THE INVENTION
Apparatus
[0099] A modified thermal plasma apparatus 100 , was used to generate fine particles in accordance with the invention. Representations of the apparatus 100 , are shown in FIGS. 1 , 2 and 16 .
[0100] A plasma torch 102 , 202 is positioned adjacent an inlet channel (not shown) and copper powder injected via the inlet channel into a plasma stream from the plasma torch 102 , 202 . The torch 102 , 202 is connected to an expansion chamber 104 , 204 which allows the copper to expand and cool. The particles of core material, in this example copper, are formed in the expansion chamber 104 , 204 . In the first example the particles flow from the expansion chamber 104 , 204 to the injection zone 106 , which includes an injection point 114 . The coating material, in this example oleic acid, is supplied to the injection zone 106 from a coating material pressurising and heating apparatus (a fluidising apparatus) 110 , via an atomiser. In this embodiment there are three injection points 114 (two only shown, the third injection point is to the rear of the apparatus). The fine particles then pass from the injection zone 106 to the cooling and collection chambers 112 .
[0101] In the second example the particles flow from the expansion chamber 104 , 204 to the coating chamber 206 which includes a control valve 228 and bypass conduit 230 ( FIG. 17 ). The coating material, in this example oleic acid, is supplied in aqueous solution in the coating chamber 206 at a concentration of 5% w/w, or in undiluted liquid form. 5% w/w. The fine particles are then retrieved and stored in collection chamber 112 .
[0102] The plasma torch 102 , 202 in the preferred embodiment is a known DC non-transferred arc torch. Other plasma torches or plasma spray torches may also be used. Gas, in this example a mixture of argon and helium, is passed between a cathode 124 and anode 126 where it is ionised and is turned into a plasma. In this embodiment the torch power is 30 kW and the flow rate of the argon/helium gas mixture is 72 litres/minute for the argon and 9 litres/minute for the helium. In further embodiments the argon gas contains up to 30% helium by volume, and/or hydrogen and/or a hydrocarbon gas such as methane or mixtures of these gases may also be used.
[0103] Preferably the plasma torch 102 , 202 has a flow stabilisation means, such as a vortex flow stabiliser (not shown) to help define the path of the plasma stream. The plasma torch 102 , 202 may also comprise a known powder feed system that is enabled to directly feed powdered material into the gas flow or into the arc of current that is created between the cathode 124 and anode 126 . In the preferred embodiment the copper core material is fed into the plasma torch as a rate of 100 g/h and the rate of argon gas flow is approximately 50 to 80 l/min.
[0104] The expansion chamber 104 , 204 of this example is frusto-conical. The expansion chamber 104 , 204 must be cooled as this chamber 104 , 204 is exposed to very high temperature plasmas, this begins the particle cooling process in which a temperature gradient is observed, the hottest region being the expansion chamber 104 , 204 , the coolest being the cooling chamber 112 , where present the injection zone 106 is positioned in between. It is the combination of expansion and cooling which allows the particles of copper to form.
[0105] In some embodiments the copper particles then flow into the injection zone 106 , where they are coated ( FIG. 3 ). The injection zone 106 is cooled, in this example using a water jacket (not shown) including water circulating at a rate of 45 litres/minute. Thus a temperature gradient is created in the injection zone 106 , the highest temperature region being adjacent to the expansion chamber 104 .
[0106] In these embodiments the oleic acid is prepared for injection into this zone 106 in a pressurising and heating apparatus ( FIG. 4 ). In this embodiment the apparatus comprises a stirred reservoir 120 of oleic acid which is heated to 73° C. (the boiling point of oleic acid is 360° C.) and pressurised to 4 bar (400 kPa). Where alternative coating materials are used, the skilled person would know to use alternative temperatures and pressures as necessary in order to reduce the viscosity of the coating material, but (in examples such as this) maintain this in liquid form prior to transfer to the atomiser. In this example the oleic acid is stored under an inert argon atmosphere. The pressurising and heating apparatus 110 is stirred using a conventional heating and stirring plate 118 . The temperature in the reservoir 120 is also controlled by the presence of an insulating jacket 116 .
[0107] The oleic acid is transferred from the pressurising and heating apparatus to the atomiser 108 ( FIG. 5 ). The atomiser 108 comprises a gas reservoir 136 , in this embodiment the gas is argon. The heated oleic acid is pumped through the atomiser 108 , out of the stainless steel nozzle 144 where it is atomised upon mixing with the argon carrier gas. The feed rate of the oleic acid in this embodiment is 605 ml/h.
[0108] In this embodiment argon enters the atomiser via a carrier gas inlet 134 and is stored in the gas reservoir 136 prior to mixing with the oleic acid. The oleic acid enters the atomiser via the coating material inlet 140 from the pressurising and heating apparatus 110 . The organic fluid passes through the atomiser via passage 142 to the nozzle 144 . The argon exits the gas reservoir through a different exit point 146 in the nozzle 144 at which point it atomises the oleic acid.
[0109] The stream of oleic acid/argon is injected at an injection point 114 where the temperature is in the range 400° C.-700° C., injection is at the point about 5° C. lower than the decomposition point of oleic acid. Injection occurs at about 5 milliseconds of copper particle formation. The stream of oleic acid/argon does not contact plasma torch 102 .
[0110] The fine particles of copper coated with oleic acid then pass through the injection zone 106 , into the cooling and collection chambers 112 . The resulting product is a fine powder of unsintered, un-agglomerate particles.
[0111] In embodiments where the coating material is liquid, the fine copper particles then flow into the coating chamber 206 where they are bubbled through the coating solution at a rate of 50 litres/minute (the main flow is typically 1,500 to 2,000 litres/minute) and at a pressure of 100 millibar gauge overpressure. Flow rate is controlled using control valve 228 , excess gas and core material being diverted directly to a gas recovery stack 232 via bypass conduit 230 . Bypass conduit 230 also functions to allow pressure relief in the event that the route to the coating chamber 206 becomes blocked.
[0112] The fine particles of copper coated with oleic acid are then collected using filtration, washed with water to ensure that all of the non-adhered coating material is removed from the coated particles and dried using conventional techniques. The resulting product is a fine powder of unsintered, un-agglomerate particles.
[0113] In optional embodiments, the carrier gas is retrieved and dried using recovery stack 232 . The gas which is retrieved may pass to the recovery stack 232 directly from the expansion chamber 204 via bypass conduit 230 (in which case the uncoated copper fine particles are filtered off before the gas is recovered), or from the coating chamber 206 (in which case the gas is retrieved via outlet 234 ). In this example the gas is drawn from the coating chamber 206 using a pump (not shown). The gas may be dried, for instance over molecular sieves, prior to reuse.
[0114] In some embodiments, bypass conduit 230 will be absent, and the whole gas stream carrying the particles may only flow via the coating chamber 206 .
[0115] Those skilled in the art will understand that the rates of coolant, bubbling, particle and gas flow may be scaled to increase or decrease the yield to be obtained, without departing from the scope of the invention. Further, in embodiments where the core and coating materials are other than copper and oleic acid, the various flow rates described above may be changed as appropriate for the substrates being used; as would be understood by the person skilled in the art.
Analytical Techniques
[0116] The SEM and STEM (cold field emission scanning STEM) images were obtained at the stated temperatures using a Hitachi S-4800 Ultra-high resolution FE-SEM (resolution to 0.6 nm). The images were obtained under low pressure vacuum.
[0117] The XRD data was obtained using a Brucker D500 defractometer at 27° C. using a step interval of 0.020° and a step time of 4 seconds. The angle range 25.0°-95.0° was swept in each instance.
Example 1
Synthesis of Fine Particles Using Injection Techniques
[0118] Powdered copper was injected into the apparatus of FIG. 1 through an alumina ring.
[0119] Oleic acid was warmed to about 50° C. and injected into the apparatus in a stream of argon. Heating the oleic acid reduced its viscosity. The acid was injected into the plasma stream at a flow rate of 25 ml/minute just above the quench ring, where the temperature was high enough to vaporise the acid, but low enough that decomposition would not occur.
[0120] After collection of the fine particles the reactor was cooled and inspected. This inspection showed that clean vaporisation of the core material had occurred and that there was no deposition of the core material on the walls of the chamber. This was attributed to the powder injection through the alumina ring. Whilst some deposition of the fine particles was observed on the filter elements, this could be removed and recovered using water or isopropanol. The recovery of agglomerated or sintered particles would require additional techniques, such as the application of ultrasound to the solvent and possibly also physical agitation.
[0121] The fine particles produced are of size in the range about 10-50 nm. Dispersions of the fine particles were stable in acetone and in ethyl acetate for at least 2 months.
Example 2
Characterisation of the Fine Particles of FIG. 1
[0122] SEM and STEM images were recorded for copper fine particles produced using the apparatus of FIG. 1 with and without an oleic acid coating.
[0123] In SEM an electron beam scans a surface and reproduces the image measured at the detector (for back-scattered (elastic) or secondary electrons, also X-rays which can give chemical mapping of the surface) onto a screen scanned in the same manner, to give a surface image at higher magnification than is possible using the frequency of light. STEM is a modification of SEM, where the apparatus is fitted with a second detector below the sample stage so that it may also be used to collect and detect electrons that pass through the sample, making it a Transmission Electron Microscope (TEM) for such samples as are sufficiently thin or which pose low resistance to the electrons for any to pass through to the detector.
[0124] The images with the coating ( FIGS. 6 to 10 ) show copper nanoparticles which are un-agglomerated and un-sintered as can be seen by the presence of distinctive black dots (the copper core) surrounded by a thin layer of a light grey material (the oleic acid coating). This is not observed with the uncoated particles ( FIGS. 11 and 12 ).
[0125] XRD images of copper fine particles with and without the oleic acid coating are also shown ( FIGS. 13 and 14 ). In XRD X-rays are directed at a surface at a range of angles, and the resulting diffracted X-rays are detected and plotted versus angle on a graph to show what materials are present, giving a chemical analysis of the surface. FIGS. 13 and 14 show that Cu(0) remains in the coated particles. Sintering of the fine particles occurs at 215° C.
Example 3
Protection of Core Material from Oxidation
[0126] Two XRD spectra were run on a copper core coated with oleic acid. These are shown in FIG. 14 (day 0—black, day 30—grey). As can be seen, the oxidation of the copper is negligible as the height of the Cu(0) peak has not varied. Accordingly, the oleic acid coating has protected the copper core from oxidation.
[0127] FIG. 15 shows two XRD spectra run on a copper core coated with PVP (day 0—black, day 30—grey). As with the oleic acid core above, the height of the Cu(0) peak has not varied, and hence the copper core has been protected from oxidation by the PVP coating.
Example 4
Synthesis of Fine Particles
[0128] Powdered copper sized between 1 and 10 micrometres was injected into the apparatus of FIG. 1 through an alumina ring. The resulting nanoparticles were then passed on a stream of argon into the coating chamber where they were bubbled through liquid oleic acid (10-20 millibar gauge) and at a rate of between 100 to 500 millilitres/minute. The coated fine particles were then collected, washed with water to remove any unbound oleic acid and dried.
[0129] It was noted that clean vaporisation of the core material had occurred and that there was no deposition of the core material on the walls of the chamber. This was attributed to the powder injection through the alumina ring. Whilst some deposition of the fine particles was observed on the filter elements, this could be removed and recovered using water or isopropanol. The recovery of agglomerated or sintered particles would require additional techniques, such as the application of ultrasound to the solvent and possibly also physical agitation.
[0130] The fine particles produced are of size in the range about 10-50 nm. Dispersions of the fine particles were stable in acetone and in ethyl acetate for at least 2 months.
Example 5
Characterisation of the Fine Particles of Example 4
[0131] The XRD image shown in FIG. 18 , includes two traces, each with a major peak (copper) just above 43, and a secondary peak (copper) just above 50 on the 2-Theta scale. The upper trace is of the oleic acid coated copper nanoparticles 30 days after formation, the lower trace is of the nanoparticles directly after synthesis. The similarity between these images, in particular the lack of copper oxide peaks appearing at around 33, 36, 37, 39, 42 and 49 on the 2-Theta scale shows that the coated particles remain oxide-free for at least 30 days.
[0132] This result can be compared with FIG. 19 (uncoated copper nanoparticles observed directly after synthesis) and FIG. 20 (uncoated copper nanoparticles after 24 hours of exposure to air). FIG. 20 clearly shows the presence of copper oxide peaks, indicating that without the protection of the coating, significant oxidation of the copper nanoparticles will take place over a short time.
[0133] SEM and STEM images, FIGS. 21 and 22 , clearly show that the coated nanoparticles of the invention are completely unagglomerated, this is contrasted with the uncoated particles of FIG. 23 which are clearly sintered.
[0134] Accordingly, the nanoparticles produced by the process of the invention have been shown to be unagglomerated and stable to oxidation over time. | A fine particle comprising a core and a coating, wherein the coating comprises a substantially monomolecular layer of organic molecules. The fine particle being produced by a process comprising introducing a core material into a plasma stream, thereby vapourising some or all of the core material; cooling the core material downstream from where the core material was introduced thereby creating particles of the core material; and coating the particles of the core material with organic molecules in an injection zone, wherein the injection zone is downstream of a region where the particles of core material are formed, or wherein the cooled particles of core material are coated with organic molecules in a coating chamber by applying a liquid coating material and/or a solution of coating material to the core material; where in the coating chamber is downstream of a region wherein the particles of core material are formed. | 1 |
BACKGROUND OF THE INVENTION
1. Field Of The Invention
The preset invention generally relates to package and article carriers. More particularly, this invention relates to an article retention system having a tether that is connected to a belt strap that encircles some part of a user's body.
2. Description Of The Related Art
Growing numbers of people appear to be concerned that they will misplace and lose valuable portable, personal articles, such as cell phones, pagers, eyeglasses, key chains and wallets. A primary reason for this situation is that more people are choosing to carry with them a greater number of more expensive personal articles, of which there are many more today than ever before, with many people preferring to have these articles at their finger tips for easy use.
Meanwhile, modern clothing is often being configured to be lighter weight and less bulky, thereby providing fewer pockets and space for transporting such personal articles. It also aes to be the case that those who prefer such clothing seldom want to be encumbered with Weighty bags for carrying personal articles; especially when such bags do not usually make such articles readily accessible, nor do they contribute to preventing the situation wherein one just forgets to put a personal article back into the bag after use.
Some work-specific items have been developed to address the related problem of providing one with easy access to items which must be transported, but always within easy reach. For example, we have a night watchman's one end of which contains a key ring, while the other end is attached to some item of the watchmans clothing's. Similarly, many tradesmen wear tool belts which allow them to have their tools constantly at-hand and ready for use.
However, these work-specific items are not well suited for general use by greater numbers of people. The need exists for better means of allowing one to transport, with minimum risk of lost valuable person articles which need to be readily accessible for ease, effectiveness and efficiency of use.
SUMMARY OF THE INVENTION
The object of the present invention is generally directed to satisfying the needs set forth above. The problems of one misplacing or losing transported, easily-accessible personal articles are minimized or resolved by the present invention.
In accordance with one preferred embodiment of the present invention, the foregoing needs can be satisfied by providing a tether with a means on one end for attaching a personal article of its user or a unit for carrying such a personal articles. The other end of the tether passes through a first connector body and is then detachably connected to a second connector body, with each of these connector bodies being attached or clamped to a user's belt or to the waist portion of a user's clothing.
This tether is positionable between an extended and a retracted position. In its retracted position, the tether encircles the waist of its user so that a personal article is held in close proximity to the waist of its user. In its extended position, the tether's detachable end is disconnected so that its other end may be moved away from the user's body to allow an attached personal article to be used more effectively.
In another embodiment, this personal article retention system further includes a second tether having the ability to attach a second personal article, while utilizing the same or similar connector bodies. In a further embodiment, these connector bodies are attached to a belt that is Worn by the system user and around which the tethers reside in their retracted position. Such a belt may be especially configured to allow it to be twice wrapped about the user's waist, with the tethers and connectors being positioned on the outer wrap of the belt.
These retention systems seen to achieve their objects of minimizing the risk that transported, readily accessible, personal articles will be lost. Other objects and advantages of this invention will become readily apparent as the invention is better understood by reference to the accompanying drawings and the detailed description that follows.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a preferred embodiment of the present invention having two tethers and two clothing attaching means ( 24 ).
FIG. 2 illustrates an embodiment similar to that shown in FIG. 1 having a second alternative clothing attaching means.
FIG. 3 illustrates an embodiment similar to that shown in FIG. 1 having a third alternative clothing attatching means.
FIG. 4 is a perspective view of a key element of the present invention: a connector body ( 22 ) that has incorporated into its design one version of a clothing attatching means ( 24 ).
FIG. 5 illustrates a key element of the present invention: a preferred version of a clothing attaching means ( 24 ) for attaching or clamping a connector body to a user's belt or the waist portion of a user's clothing.
FIGS. 6 ( a )- 6 ( c ) show top, side and perspective views of a key element of the present invention: a preferred embodiment of the present Invention's connector body and a means for coupling with a tether end.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to the drawings wherein are shown preferred embodiments and wherein like reference numerals designate like elements throughout, there is shown in FIG. 1 a preferred embodiment of a personal article retention system.
For this embodiment, the system is seen to comprise: (a) two tethers ( 10 , 40 ), each of which has two ends ( 12 , 14 and 42 , 44 ) and a central section( 16 and 46 ), respectively and each of which has a personal article attaching means ( 18 , 48 ) affixed to one of the tethers for attaching personal articles, and (b) two connector bodies ( 22 , 26 )that have respective passages ( 28 , 52 ) through which one of the tethers passes while the other tether detachably connects to the connector body, wherein each body has a clothing attaching means( 24 , 30 ) for clamping the bodies to the waist portion of the clothing of a system user, with the bodies being configured so to couple with means ( 20 , 50 ) provided at the other end of the tethers for detachably coupling these ends to the connector bodies.
The clothing attaching means( 24 , 30 ) are seen in FIGS. 1, 2 , 3 and 5 to be possible of taking many different forms, including a simple type of clasp ( 24 a , 30 a and 24 d ) and a fold over wrap ( 24 b , 30 b and 24 c , 30 c ).
These tethers are each seen to be positionable between an extended and a retracted position. In their retracted positions, the tethers are wrapped around the waist of the system user and any attached personal articles,such as a key case or wallet, are held close to the user's body. In their extended positions, the coupled tether ends are uncoupled from their connector bodies which allows their other ends with attached personal articles to be extended out from the user's body to allow for the effective use of the personal article.
Thus, to extend the personal article shown on the right side of FIG. 1, the user has decoupled the end of the tether that had been coupled to the connector body ( 22 ) shown on the left side of FIG. 1 .
FIGS. 2 and 3 illustrate alternative system embodiments that utilize differing means for clamping the connectors to clothing, including the traditional belt, worn around the waist of a system user.
All of these embodiments show the system being used with personal articles (i.e., a key case and a micro-wallet) that have been especially designed for compatibility with the system.
FIGS. 4 through 6 show, in more detail, key elements of the present invention: clothing attaching means ( 24 , 30 ) and connector bodies( 22 , 26 ). FIG. 4 shows a connector body ( 26 ) having a passage ( 28 ) through which the central section ( 16 ) of a tether passes so that its second end ( 14 ) and its personal article attaching means ( 18 ) can attach to a user's personal article of choice. Also shown are how a second tether's end ( 44 ) and its coupling means ( 50 ) detachably couples with the connector body ( 26 ). FIG. 6 shows in more detail the structure of a representative connector body and a coupling means. Meanwhile, FIG. 5 shows an alternative design for a clasping-type of clothing attaching means( 24 d ). Suitable materials of construction for these parts include plastic and metal, with their sizing being such as to be compatible with tethers constructed from materials including nylon or other plastic cordage, leather cord and woven cotton tubing.
FIGS. 12 and 13 show another version of this type of double-wrapped belt which utilizes only a single, long piece of belt and a set of D-rings ( 108 ) that enable the belt to be double-wrapped. These figures are especially noteworthy as they also show a backpack being retained by the system, with the backpack being mountable on a portion of the outer belt side that adjoins the user's back.
Although the embodiments previously disclosed have all involve their use around a user's waist, the present invention is not restricted to only such use. Other related inventions of it can be wrapped around a portion of a user's limbs or even be used to help hold and control the user's hair.
FIGS. 14 and 15 show a related invention that has been configured to be worn around the waist of its user. It consists of (a) an elongated strap ( 110 ), (b) a means ( 120 ), such as hook and loop tabs, for securing together the ends of the strap after it has been wrapped around a limb of its user, (c) a tether ( 122 ) which attaches on one end to a personal article and on the other end to the strap, and (d) a means ( 134 ), such a looped cord, slidably attached to the strap's inner for facilitating the holding of the strap while it is being wrapped around the user's limb.
FIG. 16 shows another related invention that has been configured for use in one's hair. The looped cord ( 134 ) is especially useful in this version as its user places the thumb and forefinger of one hand in the configured loops to hold one end of the strap stationary. Meanwhile, the other hand wraps the other end of the strap around a lock of hair. Materials suitable for the strap'construction include an elasticized webbing with a weave comprising raised, nappy fibers that can act as the loop end catch in a hook and loop fastener system.
Yet another related invention can be configured for use in retaining sheath instruments. FIGS. 17 and 18 show such an embodiment. It is seen to consist of: (a) cooperating straps ( 140 , 160 ) that are wrapped around the limb to which the instrument is to be restrained and placed at a separation distance which allows for support of the elongated instrument near its ends, (b) a tether ( 150 ) which attaches by suitable means ( 156 ) on one end to the exposed head of the sheathed instrument and on the other end to the strap ( 140 ) nearest the eposed head, (c) a means ( 170 ) affixed to the other strap ( 160 ) for detachably coupling the enclosing end of the instrument's sheath to this strap ( 160 ), (d) a connector ( 172 ), affixed to the strap nearest the exposed head, about which the mid-point of the tether can be held when the instrument is in its retracted position, and (e) a length-adjustable linkage ( 174 ) between the straps that provides a buffer between the sheathed instrument and one's limb, while also providing a further means ( 176 ) for detachably securing the sheath to one's limb. For instruments or tools not accompanied by sheaths, this embodiment could easily include a built-in sheath.
Materials and elements suitable for this embodiment include elasticized webbing for the strap worn at the wrist and surgical tubing for the strap worn near the elbow, a rubberized O-ring-type connector for grabbing the exposed end of the instrument, and an elastomeric catch hook about which the mid-point of the teter is wrapped.
As previously mentioned, the key case and micro-wallet that have been consistently shown throughout these figures were especially designed for compatibility with the system. More details on the construction of these articles are provided in FIG. 19 .
The key case is preferably made from a single strip of elasticized webbing, including a hidden pocket underneath the panel on which the keys are lain. Hook and loop material is used to fasten the top portion of this hidden pocket.
This especially thin wallet is preferably constructed of a single long strip (approximately 19 inches×3.5 inches) of nylon tape, folded into three, elongated panels (A, B, C). Two smaller panels (D, E) and a nylon zipper (F) act together to make a space between panels B and C into a zippered compartment. The stitching for the wallet provides for two credit card holding compartments between the remainder of panels B and C, with a paper money holding compartment between panels A and B. Two slots (G, H) are provided to enable one to dislodge tightly fitting credit cards, and hook and loop fastener materials are used for holding the folded wallet closed and for attaching it to a system belt.
Although the foregoing disclosure relates to preferred embodiments of the invention, it is understood that these details have been given for the purposes of clarification only. Various changes and modification of the invention will be apparent, to one having ordinary skill in the art without departing from the spirit and scope of the invention as hereinafter set forth in the claims. | A personal article retention system is disclosed that allows one to transport with minimum risk of loss, valuable personal articles which need to be readily accessible for effective use. In a preferred embodiment, this invention includes a tether having a means on one end that attaches to a personal article of its user. The other end of the tether passes through a first connector body and is then detachably connected to a second connector body, with each of these connector bodies being clamped on either side of the belt or waist portion of the user's clothing. | 0 |
FIELD OF THE INVENTION
The present invention relates to a process for the preparation of diesters of poly(oxyalkylene glycols) with amino acid hydrochlorides. More particularly, the present invention relates to a process for the preparation of diesters of poly (oxyalkylene glycols) and amino acid hydrochlorides having structures according to formula I below,
wherein
R 1 and R 2 are H, m is an integer from 0 to 12, or
when R 1 is H, R 2 is —CH 2 —Ph—OH or —CH 2 —SH or —CH 3 —(CH)—CH 2 —CH 3 and m is an integer equal to 1,
R is hydrogen or methyl or a mixture of hydrogen and methyl on the individual molecule, and n is an integer of from 0 to 100.
BACKGROUND OF THE INVENTION
Diesters or diamide derivatives of poly (ethylene glycols) with various amino acids are important monomers that are used in the syntheses of biodegradable polymers. E.g. Pechar et al (1997) reported synthesis of L-glutamic acid based polymeric pro-drugs wherein monomethoxy poly (oxyethylene) monocarboxylic acid was first condensed with para nitro phenol in the presence of dicyclohexylcarboxiimide (DCC) in order to activate the PEG moeity. Subsequently various oligopeptides containing L-glutamic acid were reacted with para-nitrophenyl ester of monomethoxy poly (oxyethylene) carboxylic acid. (M. Pechar, J. Strohalm and K. Ulbrich, Macromol. Chem., 198, 1009 (1997). Kohn et al (1992) reported the synthesis of water soluble poly (ether-urethane) based on PEG and L-lysine. In this, poly (ethylene glycol) was first reacted with phosgene (COCl 2 ) and then treated with N-hydroxysuccinimide in the presence of DCC to obtain activated bis (succinimidyl carbonate) derivative of PEG. This was reacted with lysine methyl ester to obtain poly (ether-urethane) (A. Nathan, D. Bolikal, N. Vyavahare, S. Zalipsky and J. Kohn, Macromolecules 25, 4476 (1992)).
Such indirect routes for linking amino acids with PEG chains were undertaken mainly due to the following reasons. Esters of amino acids are generally synthesised and stored as hydrochloride salts because esters of amino acids with free —NH 2 group are prone to undergo diketopiperazine formation. Conventional procedure for synthesis of amino acid ester hydrochloride that comprises reacting alcohol, aminoacid and thionyl chloride is not feasible for poly (ethylene glycol) because of of its bulky chain length. Thus amino acid ester hydrochloride of poly (ethylene glycol) needs to be synthesised in two steps. In the first para toluene sulfonate salt of the diester is synthesised by conventional Dean-Stark type esterification using stoichiometric amounts of amino acid, poly (ethylene glycol) and para toluene sulfonic acid monohydrate. In the second step, paratoluene sulfonate is deblocked by the treatment of base such as triethylamine or sodium bicarbonate. The free ester so synthesised is then converted into the hydrochloride salt by passing dry hydrochloride gas into solution of the ester diethyl ether.
Carbodiimides are strong condensing reagents that are routinely used in condensation reactions of N-protected amino acids. Various speciality protecting groups such as N-carbobenzoxy, N-tertiarybutyloxycarbonyl, etc. are used for this purpose. [M. Bodanzsky and A. Bodanzsky, The Practice of peptide synthesis, Springerverlag, New York, USA, (1984)]. However, the use of the hydrochloride salt as amino protecting group in carbodiimide mediated condensation reactions of amino acids has not been reported as yet.
The only reference relating to the use of amino acid hydrochloride salts as the —NH 2 protecting group in carbodiimide mediated condensation reactions was in B. S. Lele, M. A. Gore, M. G. Kulkarni, Synth. Commun. (IN Press, 1999).
OBJECTS OF THE INVENTION
Accordingly it is an object of the invention to provide a single step process for the preparation of diesters of poly (oxyalkylene glycol) and amino acids.
It is a further object of the invention to provide a process for the preparation of diesters of poly (oxyalkylene glycols) and amino acids that can be carried out under mild conditions and is generally applicable to several amino acids.
It is another object of the invention to provide a process for the preparation of diesters of poly (oxyalkylene glycols) and amino acids that allows easy esterification.
SUMMARY OF THE INVENTION
Accordingly the present invention relates to a process for the preparation of diesters of poly (ethylene glycol) of formula I below
wherein
R 1 and R 2 are H, m is an integer from 0 to 12, or
when R 1 is H, R 2 is —CH 2 —Ph—OH or —CH 2 —SH or —CH 3 —(CH)—CH 2 —CH 3 and mn is an integer equal to 1,
R is hydrogen or methyl or a mixture of hydrogen and methyl on the individual molecule, and n is an integer of from 0 to 100, said process comprising reacting poly (oxyalkylene glycol) and amino acid hydrochloride in the presence of a condensing agent in a suitable solvent at a temperature in the range of 0° C. to room temperature for a period ranging between 1 hour to 24 hours, filtering the reaction mixture, pouring the filtrate into another solvent, which is a nonsolvent for the products and isolating the precipitated products.
In one embodiment of the invention, poly(oxyalkylene glycol) may be selected from compounds of the formula HOCH 2 —CHR—(CH 2 —CHR—O—) n —CH 2 —CHR—OH wherein R is hydrogen, methyl or a mixture of hydrogen and methyl on the individual molecule, n is an interger which represents the average number of oxyalklene groups, and is preferably from 0 to 100.
In yet another embodiment of the invention, the amino acid may be selected from trifunctional and difunctional amino acids and their respective hydrochlorides.
In a further embodiment of the invention, the trifunctional amino acids are selected from tyrosine and cysteine.
In a further embodiment of the invention, the difunctional amino acids are selected from glycine, isoleucine, 6 amino caproic acid, 11 amino caproic acid.
In yet another embodiment of the invention, the condensing agent may be selected from carbodiimides such as dicyclohexyl carbodiimide, diisopropyl carbodiimide or the like.
In another embodiment of the invention, the suitable solvent may be selected from acetonitrile, tetrahydrofuran, dioxane, dimethyl formamide and the like.
DETAILED DESCRIPTION OF THE INVENTION
The process is typically carried out under mild conditions. Stoichiometric amounts of poly (oxyalkylene glycol) and amino acid hydrochloride are dissolved in a suitable solvent and the stoichiometric amount of a carbodiimide is added and the reaction mixture is stirred at room temperature for 12 hours. After this, the reaction mixture is filtered to remove the urea salts formed due to the condensation reaction. The clear solution containing the diester of poly (oxyalkylene glycol) and amino acid hydrochloride is then poured into another solvent which is a non solvent for the diester. Precipitated diester is then isolated.
The ranges and limitations provided in the present specification, examples and claims are those believed to particularly point out and distinctly cover the present invention. However, other ranges and limitations which perform substantially the same function in the same or substantially the same manner to obtain the same or substantially the same results are intended to be within the scope of the instant invention. The process of the present invention will be further described by the following examples which are provided for illustration and are not to be construed as limiting the invention.
EXAMPLE 1
Preparation of bis (tyrosyl hydrochloride) poly (ethylene glycol) 6000 diester (Bis tyr.HCl−PEG 6000)
In a 100 ml capacity conical flask, 6 g PEG 6000 (0.001 M), 0.435 g (0.002 M) tyr.HCl, and 10 ml DMF were taken. The contents of the flask were gently heated to dissolve the solids and obtain a clear solution. To this solution, 0.412 g DCC (0.002 M) dissolved in 5 ml DMF was added in a single portion. The reaction mixture was stirred at room temperature (25° C.) for 24 hours. It was then filtered to separate out dicyclohexyl urea (DCU) formed and the clear solution was poured into a 200 ml diethyl ether to precipitate out white powdery product. The product was isolated and purified by reprecipitation from methanol into diethyl ether.
Yield (78%)
EXAMPLE 2
Preparation of bis (cistyl hydrochloride) poly (ethylene glycol) 6000 diester (Bis cyst.HCl−PEG 6000)
In a 100 ml capacity conical flask, 6 g PEG 6000 (0.001 M), 0.3 15 g (0.002M) cyst.HCl, and 10 ml DMF were taken. The contents of the flask were gently heated to dissolve the solids and obtain a clear solution. To this solution, 0.412 g DCC (0.002 M) dissolved in 5 ml DMF was added in a single portion. The reaction mixture was stirred at room temperature (25° C.) for 24 hours. It was then filtered to separate out dicyclohexyl urea (DCU) formed and the clear solution was poured into a 200 ml diethyl ether to precipitate out white powdery product. The product was isolated and purified by reprecipitation from methanol into diethyl ether.
Yield (70%)
EXAMPLE 3
Preparation of bis (isaoleucyl hydrochloride) poly (ethylene glycol) 6000 diester (Bis isoleu.HCl−PEG 6000)
In a 100 ml capacity conical flask, 6 g PEG 6000 (0.001 M), 0.335 g (0.002 M) isoleu.HCl, and 10 ml DMF were taken. The contents of the flask were gently heated to dissolve the solids and obtain a clear solution. To this solution, 0.412 g DCC (0.002 M) dissolved in 5 ml DMF was added in a single portion. The reaction mixture was stirred at room temperature (25° C.) for 24 hours. It was then filtered to separate out dicyclohexyl urea (DCU) formed and the clear solution was poured into a 200 ml diethyl ether to precipitate out white powdery product. The product was isolated and purified by reprecipitation from methanol into diethyl ether.
Yield (68%)
EXAMPLE 4
Preparation of bis (6 amino caproyl hydrochloride) poly (ethylene glycol) 6000 diester (Bis 6ACA.HCl−PEG 6000)
In a 100 ml capacity conical flask, 6 g PEG 6000 (0.001 M), 0.335 g (0.002 M) 6ACA.HCl, and 10 ml DMF were taken. The contents of the flask were gently heated to dissolve the solids and obtain a clear solution. To this solution, 0.412 g DCC (0.002 M) dissolved in 5 ml DMF was added in a single portion. The reaction mixture was stirred at room temperature (25° C.) for 24 hours. It was then filtered to separate out dicyclohexyl urea (DCU) formed and the clear solution was poured into a 200 ml diethyl ether to precipitate out white powdery product. The product was isolated and purified by reprecipitation from methanol into diethyl ether.
Yield (80%)
EXAMPLE 5
Preparation of bis (glycyl hydrochloride) poly (ethylene glycol) 6000 diester (Bis gly.HCl−PEG 6000)
In a 100 ml capacity conical flask, 6 g PEG 6000 (0.001 M), 0.223 g (0.002 M) gly.HCl, and 10 ml DMF were taken. The contents of the flask were gently heated to dissolve the solids and obtain a clear solution. To this solution, 0.412 g DCC (0.002 M) dissolved in 5 ml DMFf was added in a single portion. The reaction mixture was stirred at room temperature (25° C.) for 24 hours. It was then filtered to separate out dicyclohexyl urea (DCU) formed and the clear solution was poured into a 200 ml diethyl ether to precipitate out white powdery product. The product was isolated and purified by reprecipitation from methanol into diethyl ether.
Yield (82%)
EXAMPLE 6
Preparation of bis (11 amino undecanoyl hydrochloride) poly (ethylene glycol) 6000 diester (Bis 11AU.HCl−PEG 6000)
In a 100 ml capacity conical flask, 6 g PEG 6000 (0.001 M), 0.475 g (0.002 M) 11AU.HCl, and 10 ml DMF were taken. The contents of the flask were gently heated to dissolve the solids and obtain a clear solution. To this solution, 0.412 g DCC (0.002 M) dissolved in 5 ml DMF was added in a single portion. The reaction mixture was stirred at room temperature 25° C.) for 24 hours. It was then filtered to separate out dicyclohexyl urea (DCU) formed and the clear solution was poured into a 200 ml diethyl ether to precipitate out white powdery product. The product was isolated and purified by reprecipitation from methanol into diethyl ether.
Yield (80%)
Quantification of hydrochloride salt present in the diesters was done by determining their acid values. Data for acid values of all compounds are listed in Table 1 show that theoretical and found acid values are in close agreement, taking into consideration the polydispersity in commercial PEG samples used.
Acid values
Acid values
milimoles HCl/g
milimoles HCl/g
No.
Diester
(calculated)*
(found)
1
Bis tyr.HCl - PEG6000
0.2 to 0.3
0.224
2
Bis cyst.HCl - PEG 6000
0.2 to 0.3
0.29
3
Bis isoleu.HCl - PEG6000
0.2 to 0.3
0.213
4
Bis 6ACA.HCl - PEG6000
0.2 to 0.3
0.224
5
Bis gly.HCl - PEG6000
0.2 to 0.3
0.254
6
Bis 11AU.HCl - PEG6000
0.2 to 0.3
0.26
*Acid values calculated for PEG 6000 with molecular weight range 6000 to 7500
Advantages of the Invention
1. The process is carried out under mild conditions and is generally applicabble to various amino acids.
2. Fatty alcohols that are otherwise difficult to esterify by conventional methods, can be easily esterified using the process of the present invention.
3. The use of the hydrochloride salt as —NH 2 protecting group can be extended in various other carbodiimide mediated condensation reactions using amino acids. | The present invention relates to a process for the preparation of diesters of poly (ethylene glycol) by reacting poly (oxyalkylene glycol) and amino acid hydrochloride in the presence of a condensing agent in a suitable solvent at a temperature in the range of 0° C. to room temperature for a period ranging between 1 hour to 24 hours. The reaction mixture is then filtered and the filtrate poured into another solvent, which is a nonsolvent for the products. The products precipitated thereby are then isolated. | 2 |
This is a continuation of copending application Ser. No. 07/602,011 filed on Oct. 23, 1990 now abandoned.
This invention relates to a method for producing laminated structural panels and the resulting panels.
BACKGROUND OF THE INVENTION
There has long been a need for materials which combine the desirable qualities of reasonable strength, good stiffness and load carrying ability, and good sound and temperature insulation with substantially less weight than solid members of the same materials. Most of such structures are of a type known as honeycomb materials. Such materials are often formed of numerous connected cells of organic material such as paper or wood as the internal structure with wood, glass fiber, or metal exterior plates fastened to the ends of the cells, typically with a suitable glue such as an epoxy resin. All metal honeycomb structure is also known wherein interconnected cells of thin wall metal are fastened by suitable means, to exterior plates. Such a honeycomb structure is shown and described in U.S. Pat. No. 4,013,210. This patent also describes a vacuum diffusion bonding process for fastening the metal honeycomb structure to face sheets or plates. The process and resulting product seem to be directed principally to forming titanium bodies. Other patents teach the use of epoxy of some type as the bonding media, e.g. U.S. Pat. Nos. 4,692,367 and 4,063,981. U.S. Pat. No. 4,622,445 teaches a process for brazing a metal face sheet to a honeycomb core wherein a brazing alloy is placed between the face sheet and the core and the face sheet pressed to the core with a piece of thermal insulation while the metal parts are heated to a temperature just sufficient to melt the brazing alloy. An inert gas is provided as an environment during the heating process.
The problem with such honeycomb structures is that, in general, they are relatively fragile; if bonded with epoxy they are quite limited in the temperature and atmospheric pressure changes to which they may be exposed, they cannot normally be made thinner than about 0.25 inch, and once so constructed they cannot be processed further to conform to other shapes, as by rolling, forming, bending, etc. Due to temperature or pressure stress, delamination often occurs causing moisture absorption resulting in internal corrosion. There is a need for an all metal laminated structure providing good sound and thermal insulation which is essentially as strong as a homogeneous metal panel of the same thickness, but substantially lighter in weight, which is essentially immune to internal corrosion, which can be subjected to essentially all the same metal forming processes as homogeneous metal, which may be repaired or fabricated by welding similarly to homogeneous metal, and in which any cuts or punctures affect only the cells directly involved because each entrained cell is effectively vacuum sealed from all the others.
BRIEF DESCRIPTION OF THE INVENTION
The method and resulting structural panels described herein utilize a stack of metal plates wherein the face plates, or top and bottom plates are solid and the center plates are perforated to produce a substantial number of openings. The perforations may be formed by drilling, cutting, chemical etching, stamping or other machining processes capable of producing the desired pattern of openings. The process described herein is applicable to many combinations of metals, which may be selected according to the application for the panel. As an example, a typical panel may be formed with top and bottom face sheets and center sheets of aluminum which may be clad with an aluminum brazing material or the sheets may be interleaved with aluminum brazing foil.
The stack is then placed in an oven and brazed at a high vacuum and at a temperature sufficient to melt the brazing material. The brazing process itself is known and those skilled in the art will be aware of suitable temperatures and vacuum values for brazing other materials.
By selecting a pattern of perforations and number of internal layers, laminated panels may be made as thin as 0.010 inch or substantially thicker as desired. They may be laminated with fluid channels to conduct coolant or lubricants and they may be subjected to additional metal working steps such as welding, stamping, sawing, forming, rolling, etc., in essentially the same manner as homogeneous metal panels.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a plan view, partly broken away, of a lightweight structural panel formed according to my invention;
FIG. 2 is a fragmentary exploded view of the structural panel of FIG. 1;
FIG. 3 is a partial edge view of an alternate form of structural panel according to my invention;
FIG. 4 is a plan view, partly broken away, of another embodiment of my invention;
FIG. 5 is a sectional view taken along line 5--5 of FIG. 4;
FIG. 6 is a perspective view, partly broken away, of another embodiment of my invention; and
FIG. 7 is a sectional view taken along line 7--7 of FIG. 6.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to FIG. 1, a laminated panel 10 is described and according to my invention includes a plurality of sheets of aluminum alloy 12 which are perforated to a desired pattern and which are joined using a brazing process to an upper face sheet 16 and a bottom or lower face sheet 18 (FIG. 2). The pattern of perforation and the number of perforated sheets may be selected to control the density or stiffness of the panel 10. FIG. 2 is an exploded view, partly broken away, of a simple laminated structure such as shown in FIG. 1 formed of four sheets 12, 14, 16 and 18 of aluminum alloy, the center ones 12 and 16 being perforated and either clad with aluminum brazing material or interleaved with aluminum brazing foil as described above.
FIG. 3 is a fragmentary cross sectional view of a laminated structure formed of several layers, but which, in plan view could appear similar to FIG. 1. In FIG. 3 are shown face sheets 20 and 22, perforated sheets 24, 26 and 28 and a pair of unperforated sheets 30 and 32 interleaved between the perforated sheets. All of these stacked sheets are brazed together to provide a comparatively lightweight structure which is quite stiff and strong and which can be further processed in essentially the same manner as could a solid sheet of the same aluminum alloy. The use of the unperforated internal sheets is optional and would depend on requirements.
FIG. 4 is a plan view, with the top sheet partly broken away and with other parts shown in phantom, of another embodiment of my invention of my invention. This laminated stacked assembly 38 includes a top face sheet 40, a bottom face sheet (not shown) and one or a plurality of internal sheets 42 which are stacked and brazed together with the face sheets to form a panel permitting the passage of a liquid such as a lubricant or a coolant. In this embodiment a plurality of elongated perforations 44 are spaced from a liquid flow channel 46 which is folded back and forth (in this case, eight times) between an inlet port 48 and an outlet port 50. The internal member 42 could be a single machined piece or a laminated stack of similar sheets of sufficient thickness to provide the desired flow area. FIG. 5 is a fragmentary cross sectional view taken along line 5--5 of FIG. 4 showing the top face sheet 40, internal member 42 and a bottom face sheet 52.
FIG. 6 is a perspective view, shown partly broken away, of another embodiment of my invention wherein the lower face member 60 is an etched or machined plate of significant thickness formed with a plurality of alternating wide and narrow channels 62, 64 respectively, each opening into a hollowed out manifold section 66. An inlet port 68 connects manifold section 66 with a source of fluid. An outlet port (not shown) may be located at the opposite end of the panel. The narrow channels 64 are fluid channels which communicate manifold 66 and inlet port 68 with the outlet port. Filling each of the wide channels 62 is a stack 70 of perforated strip members which may be laminated as a stack before being placed in channels 62, or they may be individually laid in channels 62. A face sheet 72 is then placed on the top of the assembly which is then brazed together to fabricate an integrated panel.
FIG. 7 is a sectional view taken along line 7--7 of FIG. 6 and shows lower face member 60, upper face sheet 72 (unattached in this view), channels 62 with stacks 70 of perforated strip members and fluid channels 64. As will be apparent to those skilled in the art, the fluid channels 62 may each terminate in a manifold like manifold 60 or the structure shown in FIGS. 6 and 7 may be made with channels 64 interconnected as in FIG. 4. Many other configurations or perforations with or without fluid channels are possible depending upon requirements. The teachings herein also contemplate that panels may be made with such a large percentage of their volume in vacuum filled cells that the panels will float in water.
Laminated panels such as those described above are formed essentially as follows in the case of panels of aluminum alloy. The stack when assembled as desired is then placed in an oven and initially subjected to a vacuum such as 200 microns at which time the oven is backfilled with an inert gas to remove most of the oxygen. At this time the oven is heated to approximately 225° F. plus or minus 20° F. The vacuum is then increased to about 10 -5 Torr and the temperature raised to a brazing temperature which in the case of the aluminum and aluminum brazing material is about 1100° F. When the stack has reached an average temperature of 1100° F. The oven is turned off and the stack permitted to cool slowly to 1065° F. or lower, at which time the stack can be removed from the oven. The brazing process itself is known and those skilled in the art will be able to select suitable temperatures and various readings for brazing other materials.
Laminated panels as described can be fabricated of titanium or titanium alloys with aluminum brazing material, of stainless steel with silver brazing material, of nickel with nickel or aluminum brazing material, and others. This listing is exemplary only and not intended to be exhaustive. Dissimilar metals and cladded metals might be chosen where special characteristics are required, e.g., where high strength is required in combination with resistance to high temperatures and corrosion, a nickel alloy face sheet, a nickel alloy perforated core material and a titanium face sheet with gold brazing alloy material may be used. Other such combination of metals and cladding materials include nickel alloy such as Inconel clad with silver, stainless steel clad with aluminum or titanium clad with aluminum.
The resulting laminated panel may then be further formed as desired and heat treated. The density of the laminate is controllable within a wide range by varying the number and pattern of perforations, per sheet and the number of perforated sheets. It is also possible to form fluid channels in the internal layers for cooling or for the transfer of hydraulic fluid. Also, some internal sheets may be unperforated if additional stiffness or isolation of the entrained spaces is desired. Normally the edges of the internal sheets are left solid and are brazed to provide an integral frame as compared with a honeycomb structure wherein the frame is bonded or riveted to the honeycomb core.
The laminated structure described above provides additional benefits in that structural loading is uninterrupted and evenly distributed from the outside edges to the center of the panel and by arranging the panels with the granular structure or grain of individual panels at right angles or non-parallel to each other, overall structural integrity is improved.
Those skilled in the art will recognize that many possible configurations of panels are possible utilizing the teachings herein. Stiffness and density are variable depending upon the number of intermediate perforated layers and the pattern of perforations in such layers. Various materials and combinations of materials are possible as set forth above; consequently, I do not desire to be limited to the embodiments described but only by the following claims as interpreted with the benefit of the doctrine of equivalents. | Laminated structural panels and the method of producing them involve selection of a desired member of sheets of sheet metal of the desired thickness and material, perforating one or more of the sheets to a desired pattern depending upon characteristics desired such as lightness, stiffness or inclusion of fluid passageways etc., stacking the perforated sheets with imperforate face sheets top and bottom and, with brazing material at the interface between the sheets, subjecting the stack to a temperature high enough to cause melting of the brazing material while maintaining a very high vacuum environment. In an alternative embodiment, one or more imperforate internal sheets may be interleaved between the perforated sheets. | 1 |
RELATED APPLICATION
The present application claims priority to French Application No. 09 54963 filed Jul. 17, 2009, which is incorporated herein in its entirety by reference.
TECHNICAL FIELD
The present invention relates to a fiber application machine for the production of parts made of composite materials, and more particularly, such a machine comprising a fiber heating system and a heat-resistant compacting roller.
BACKGROUND ART
There have been known fiber application machines, for applying on an application surface of a male or female mold, a wide band formed of at least a ribbon-type resin pre-impregnated flat fiber, particularly carbon fibers pre-impregnated with a thermoplastic or thermosetting resin, and particularly so-called fiber placement machines for applying a wide band formed of a plurality of resin pre-impregnated fibers.
These fiber placement machines, such as described in patent document WO2006/092514 typically comprise a fiber placement head and a system for moving said fiber application head. Typically, said fiber placement head comprises a compacting roller for contacting the mold so as to apply the pre-impregnated fiber band, a guiding assembly for guiding fibers in the form of a band over said compacting roller, and a heating system for heating the pre-impregnated fibers.
The compacting roller presses the fiber band against the mold application surface, or against the fiber band or bands deposited beforehand, such that the adhesion of the deposited bands between each other is facilitated, and air trapped between the deposited bands is progressively discharged.
The heating system heats the pre-impregnated fiber band, and/or the mold or the bands already applied upstream of the compacting roller, just before the compacting of the band, so as to at least soften the resin and thus promote the adhesion of the bands between each other. Generally, the band heating system provides at least the heating of the band just before its compacting.
In order to ensure a substantially uniform compacting over the entire width of the band, the fiber placement head advantageously comprises a compacting roller able to adapt to the application surface, and preferably, a compacting roller made of a flexible material, which is elastically deformable, generally, an elastomeric material.
In the case of thermosetting resins, the pre-impregnated fibers are only heated to be softened, typically at temperatures of about 40° C. At these temperatures, an elastomeric material flexible roller may advantageously be used. After applying several layers of superimposed bands, the resulting part is vacuum hardened, through polymerization, by passing it within a furnace, generally an autoclave furnace.
In the case of thermoplastic resins, the pre-impregnated fibers have to be heated at higher temperatures, at least up to the resin melting temperature, that is, of about 200° C. for nylon type resins, and of about 400° C. for PEEK type resins. A hardening operation, called consolidation operation, of the resulting part is advantageously carried out thereafter by passing it within a furnace.
The heating carried out during the application of the band may be implemented through a laser type heating system so as to obtain a concentrated and sharp heating. Owing to the high heating temperatures, the fiber placement heads are provided with heat resistant metallic compacting rollers which may also be cooled from inside via a waterway.
To adapt to the profile of the application surface, there have been proposed segmented metallic compacting rollers, comprising several independent roller segments mounted abreast on a same axis, each segment being independently and radially movable, and being elastically biased against the application surface. Nevertheless, the structure of such segmented metallic rollers and their implementation proved to be complex.
Flexible rollers formed from a so called high temperature elastomeric material, including a heat stabilizer, have also been tested. Nevertheless, theses rollers proved to be unsatisfactory for the implementation of thermoplastic resins.
To make it possible to use a flexible roller at the operating temperatures of the thermoplastic resins, there has been proposed, notably in patent document FR 2 878 779, a head provided with two compacting rollers with a heating system acting between both rollers and outputting a heat radiation substantially perpendicular to the band, between both rollers. Such a dual roller head exhibits a greater encumbrance inhibiting fiber deposition on certain application surface profiles. Moreover, the heating of the bands deposited beforehand for their adhesion through welding to the newly applied band is only made through thermal conduction, which constitutes a restrictive factor for the fiber application speed.
SUMMARY OF THE INVENTION
The present invention is aimed to provide a solution overcoming the aforementioned drawbacks, particularly making it possible to implement a wide variety of resins, ranging from thermosetting to thermoplastic ones, with a substantially uniform compacting of the applied band and which can be designed and made easily.
To this end, an embodiment of the present invention is a fiber application machine for the production of parts made of composite materials comprising:
a compacting roller for applying on an application surface a band formed of at least a resin pre-impregnated flat fiber, preferably formed of a plurality of resin pre-impregnated flat fibers, the compacting roller comprising a rigid central tube whereby the roller is rotationally mounted on a support structure of the machine, and a cylinder made of an elastically deformable, flexible or non-rigid material, coaxially assembled on the central tube; and a heating system adapted to emit a heat radiation towards the band, just before the compacting thereof by the compacting roller;
the central tube being provided with radial holes, the flexible material cylinder having a fluid communication system adapted to establish fluid communication between the radial holes and the external surface of the cylinder, the machine comprising a thermal regulation system adapted to inject a thermal regulation fluid, preferably gaseous, in the internal passage of the central tube.
According to an embodiment of the invention, the machine comprises a flexible compacting roller thermally regulated by a thermal regulation system by circulation of a thermal regulation fluid. The thermal regulation system comprises:
holes made in the tubular wall of the central tube, traversing it from end to end, the central tube being for example metallic and/or of cylindrical cross-section, a fluid communication assembly adapted to provide at the flexible material cylinder the circulation of a thermal regulation fluid through the cylinder, from the radial holes towards the external surface of the cylinder, and a thermal regulation system adapted to inject a thermal regulation fluid, preferably gaseous, advantageously a cooled or room temperature gas, particularly air, within the internal passage of the central tube from at least one end thereof, the thermal regulation fluid passes through the radial holes, traverses the flexible material cylinder to reach its external surface.
In the case of a thermal regulation fluid at room temperature, at, for example, between 15° C. and 30° C., or cooled at a temperature lower than 15° C., the circulation of the thermal regulation fluid in the compacting roller makes it possible to cool the compacting roller on the surface, as well as over the thickness of the flexible material cylinder and thus makes it possible to use a stable, flexible material compacting roller which can be used for the application of fibers pre-impregnated with resins, particularly, thermoplastic resins. The machine according to the invention, which comprises a compacting roller of simple design, makes it possible to use a wide variety of thermosetting or thermoplastic resins in combination with a wide range of synthetic or natural, hybrid or non-hybrid fibers, particularly, fibers usually used in the composite field, such as glass fibers, carbon, quartz, and aramid fibers.
The fluid communication can be adapted to establish a fluid communication between the external surface of the cylinder and the lateral sides of the compacting roller, so as to discharge to the outside the thermal regulation fluid at least laterally during the operation of the machine.
According to one embodiment, the fluid communication system includes radial channels, each radial channel opening onto a radial hole of the central tube and onto the cylinder external surface. The radial holes are distributed over the cylindrical wall of the central tube. For example, the central tube exhibits several sets of holes offset in the longitudinal direction along the axis of the compacting roller, each set comprising a plurality of holes made at regular angular intervals.
According to one embodiment, the fluid communication system includes longitudinal grooves opening onto the cylinder lateral sides, the radial channels opening onto the longitudinal grooves. So as to achieve a better distribution of the thermal regulation fluid flux on the external surface, the fluid communication system advantageously includes circular grooves onto which the radial channels open.
According to one embodiment, the fluid communication system includes the porous nature of the material constituting the cylinder, the fluid communication system then comprising a cylinder made of an elastically deformable, porous flexible material such as an open cells elastomeric and/or thermoplastic cellular foam, or a material made of non-woven fibers, such as synthetic fibers, glass fibers or metallic fibers, preferably an open cell-type elastomeric foam. In this case, the discharge of the thermal regulation fluid takes place through the lateral sides of the cylinder.
According to one embodiment, the fluid communication system comprises a sheath covering the external surface of the cylinder, the sheath being made of a porous material, thus making it possible to discharge the thermal regulation fluid by the lateral sides of the sheath. The porous material is made, for example, of an open cell-type thermoplastic and/or elastomeric foam, or a non-woven fiber material. The porous material of the sheath is elastically deformable so as to conform to the cylinder deformation during the fiber application, but exhibits a lower elasticity than that of the flexible, and possibly porous, material constituting the cylinder so as to allow for the discharging of the thermal regulation fluid.
According to one embodiment, the roller comprises a shielding sheath covering the cylinder and forming a shield against the heat radiation emitted by the heating system, the shielding sheath being formed, for example, from a glass fiber fabric.
This shielding sheath makes it possible to avoid the heat build-up of the compacting roller over the entire thickness thereof owing to the heat radiation of the heating system directed towards the compacting roller. This shielding sheath absorbs and/or reflects the heat radiation, the thermal regulation fluid thus serving for the cooling of this shielding sheath so as to avoid a heat build-up, by conduction, of the cylinder.
In the case of fiber placement, the machine typically includes a cutting assembly making it possible to individually cut the fibers upstream of the compacting roller and rerouting assembly, disposed upstream of the cutting means, for rerouting each fiber that has just been cut towards the compacting roller so as to be able to stop and resume the band application at any time, as well as varying the applied band width. When the width of the applied band is reduced, for example, of only 10 fibers for a 16 or 32 fibers-type placement head, the roller directly receives the heat radiation, with no fibers interposed between the heat source and the roller. The shielding sheath makes it possible to avoid the high heat build-up due to this direct heat radiation.
According to one embodiment, as an alternative to the shielding sheath, or in combination therewith, the cylinder is made of a material substantially transparent to the heat radiation such as described in the French patent application 09 54964 filed by the applicant, on the same day as the French priority date of the present application, and entitled “Fiber application machine with compacting roller transparent to the radiation of the heating system”, and filed in the United States with application Ser. No. 12/628,460, on the same date as the present application, incorporated herein by reference. In this specification, material “substantially transparent to heat radiation” means a material exhibiting a low absorbance in the wavelength or wavelengths of the heat radiation. According to one embodiment, the flexible material is an elastomeric material. Preferably, the flexible material is a silicone or polysiloxane, or polyurethane, preferably a silicone. The heating system can emit infrared radiation having a wavelength between 780 nm and 1500 nm; the elastically deformable material presents a low absorbance at least in this wavelength range of between 780 nm and 1500 nm. Preferably, the heating system emits an infrared radiation of wavelength between 850 nm and 1100 nm.
According to one embodiment, the compacting roller comprises an anti-adherent external layer coating said flexible material cylinder, when the roller comprises a sheath made of a porous material, and/or a shielding sheath, the latter being interposed between the cylinder and the anti-adherent external layer, the anti-adherent external layer being advantageously formed of an anti-adherent film, such as a PTFE (polytetrafluoroethylene) film, which is for example thermally retracted on the cylinder. PTFE is well known by the DuPont brand name Teflon®. In this case also, the thermal regulation fluid regulates the temperature of the anti-adherent external layer.
According to one embodiment, the heating system is a laser-type system, particularly laser diode type, a YAG laser type or a fiber laser type. Alternatively, the heating system may comprise one or more infrared lamps.
According to one embodiment, the machine further comprises thermal regulation system adapted to output a thermal regulation fluid flux, particularly air, towards the compacting roller so as to regulate the temperature of said compacting roller, and in particular to cool the compacting roller, from the outside. In this case, the thermal regulation of the roller is carried out from inside the roller and from outside the compacting roller, preferably, with a same thermal regulation fluid, preferably air.
According to one embodiment, said thermal regulation means are able to inject a thermal regulation fluid at room temperature, preferably between 15° C. and 30° C., or a thermal regulation fluid cooled at a temperature lower than 15° C., preferably a cooled or room temperature gas, preferably, air at room temperature, so as to cool the compacting roller.
The present invention is also aimed to provide a compacting roller such as is described above, for a fiber application machine, comprising a rigid central tube made of an elastically deformable, flexible or non-rigid material, assembled on the central tube, and particularly characterized in that the central tube is provided with radial holes, the flexible material cylinder having a fluid communication system able to bring the holes into fluid communication with the external surface of said cylinder.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be better understood, and other aims, details, features and advantages will become more apparent from the following detailed explanatory description of currently preferred particular embodiments of the invention, with reference to the accompanying schematic drawings in which:
FIG. 1 is a schematic side view of a fiber application head according to a first embodiment of the invention, comprising a compacting roller and a heating system;
FIG. 2 is a perspective view of the compacting roller of the machine of FIG. 1 ;
FIGS. 3A and 3B are transversal and longitudinal side views, with partial cut-out, of the compacting roller of FIG. 2 ;
FIG. 4 is a perspective view of a compacting roller of a machine according to a second embodiment;
FIGS. 5A and 5B are transversal and longitudinal side views, with partial cut-out, of the compacting roller of FIG. 4 ;
FIG. 6 is a perspective view of a compacting roller of a machine according to a third embodiment;
FIG. 7 is a longitudinal side view of the compacting roller of FIG. 6 with partial cut-out;
FIG. 8 is a perspective view of a compacting roller of a machine according to a fourth embodiment; and
FIG. 9 is a longitudinal side view, with partial cut-out, of the compacting roller if FIG. 8 .
DETAILED DESCRIPTION
With reference to FIG. 1 , the fiber application machine comprises an application head 1 for applying a band 8 of resin pre-impregnated fibers, said head including a compacting roller 2 which is rotationally mounted about an axis A on a support structure (not shown) of the head, the head being mounted by said support structure at the end of a moving system, for example, a robot wrist-joint.
The head further comprises a heating system 9 also mounted on the support structure upstream of the roller with regard to the progress direction D of the application head during the application of fiber band 8 on an application surface S. For example, the heating device is a laser type heating system, of which radiation is directed towards the band, just before the compacting thereof, as well as towards the band or bands deposited beforehand. As illustrated in FIG. 1 , the radiation is thus obliquely directed towards the roller so as to heat a band section disposed on the roller, before the compacting thereof by the roller.
In the case of a fiber placement machine, the head comprises a guiding assembly for guiding the fibers incoming into the head towards the compacting roller 2 in the form of a band of resin pre-impregnated fibers, the fibers of the band being disposed abreast in a substantially butt-jointed fashion. By moving the head via the robot, the compacting roller is brought into contact with the application surface S of a mold for applying the band.
With reference to FIGS. 2 , 3 A and 3 B, the compacting roller according to an embodiment of the invention comprises a cylindrical body or cylinder 3 made of a flexible material, elastically deformable by compression. The cylinder exhibits a cylindrical central passage 31 for its assembly on a support core formed of a cylindrical rigid central tube 4 , for example, a metallic tube, such as in aluminum. Cylinder 3 and central tube 4 are coaxial to each other and rotate integrally with each other. For example, the cylinder is composed of a non-expanded elastomeric material, such as silicone, polysiloxane or polyurethane.
The flexible material cylinder allows the compacting roller to adapt to the application surface curvature variations and to thus apply a substantially uniform pressure on the entire deposited band. The rigid tube makes it possible to rotationally mount the roller on the support structure.
The central tube is provided with radial holes 41 , for example, cylindrical holes, traversing the cylindrical wall of the central tube from end to end. Thus, the radial holes open onto central tube internal passage 42 and onto the cylinder. The cylinder is provided with radial channels 32 , aligned with the radial holes, and of which diameters are substantially identical to those of said radial holes. In the illustrated example, the central tube comprises six sets of radial holes 41 longitudinally offset along axis A of the roller, each set comprising a plurality of radial holes disposed at regular angular intervals, for example, eight radial holes spaced apart by 45° from each other. The cylinder then comprises six sets of radial channels 32 each comprising eight radial channels spaced apart by 45° from each other.
Each radial channel 32 opens onto the cylindrical external surface 33 of cylinder 3 , at the intersection of a longitudinal groove 34 and a circular groove 35 . The longitudinal grooves 34 , in the case of eight grooves, extend over the entire length of the cylinder from one lateral side 36 of the cylinder to the other.
Externally, the cylinder is coated with an anti-adherent external layer 5 , formed here of a PTFE film thermally retracted on the external surface of the cylinder. The PTFE film thereby covers the longitudinal grooves and the circular grooves made on the cylinder external surface. The PTFE film through which the roller contacts the band, restricts the adherence of the roller to the fibers as well as the fouling of the roller.
The compacting roller is mounted by the open ends 43 of its central tube, for example, between two flanges of the head support structure. The machine comprises a thermal regulation system (not shown), which enables the injection of a gas at room temperature, between 15 and 30° C., or a gas cooled at to a temperature lower than 15° C., particularly air, from one open end 43 of central tube. This air injection is carried out by means of a conventional swing joint system. The central tube advantageously has a spot facing 44 for mounting the swing joint system. In operation, the air injected from at least one open end 43 of central tube, passes within the radial holes 41 then the cylinder radial channels 32 to distribute in the circular and longitudinal grooves 35 and 34 , and leak from the lateral sides 36 of the cylinder onto which the longitudinal grooves open. Advantageously, the thermal regulation fluid is cooled air or air at room temperature, preferably air at room temperature, so as to cool the compacting roller and keep it at a temperature of about 30° C.
Alternatively, the cylinder may be made of a flexible material, substantially transparent to the radiation emitted from the heating system.
For example, the flexible material substantially transparent to heat radiation is a silicone-type elastomeric material, particularly silicone elastomer sold by Dow Corning under the commercial denomination Silastic T-4.
The laser-type heating system may comprise laser diodes, disposed in one or more rows, emitting a radiation presenting a wavelength of between 880 and 1300 nm, for example, an optical fiber laser or YAG laser, emitting at a wavelength of about 1060 nm.
To complete the thermal regulation of the roller from the inside, the thermal regulation system may further comprise a thermal regulation system able to output an air flux, towards the compacting roller, so as to also cool the compacting roller from outside.
FIGS. 4 , 5 A, and 5 B illustrate a second embodiment of the invention in which the compacting roller 102 comprises, as previously, a rigid central tube 104 provided with radial holes 141 , a cylinder 103 made of a flexible, elastically deformable material, provided with radial channels 132 . In this example, the circular longitudinal grooves described above, intended to enhance the distribution of the air flux injected on the cylinder surface and its leaking from the lateral sides of the cylinder, are replaced by a sheath 106 covering the cylinder external surface 133 , the sheath being made of a porous material, such as an open-cell type thermoplastic and/or elastomeric foam, or a material made of non woven fibers. This porous material exhibits elasticity so as to conform to the cylinder deformation during the pressing of the roller against the application surface. An anti-adherent external sheath 105 covers the porous material sheath. After passing within the internal passage 142 and the radial holes 141 of central tube 104 , then in the cylinder radial channels 132 , the injected air passes through the porous material sheath and leaks laterally from the lateral sides 161 of the sheath.
FIGS. 6 and 7 illustrate a third embodiment of the invention in which the compacting roller 202 comprises, as in the first embodiment, a rigid central tube 204 provided with radial holes 241 , an elastically deformable, flexible material cylinder 203 , and an anti-adherent external sheath 205 covering the cylinder external surface 233 . In this embodiment, the cylinder is not provided with radial channels, but constituted by a porous, flexible, elastically deformable material. The injected air, which exits from the internal passage 242 of central tube 204 through the radial holes 241 , traverses the entire porous cylinder and leaks from the cylinder lateral sides 236 . The flexible porous material is an open-cell type thermoplastic and/or elastomeric foam, or a material made of non woven fibers, for example, an open-cell type elastomeric foam.
FIGS. 6 and 7 illustrate a fourth embodiment of the invention in which the compacting roller 302 comprises, as in the third embodiment, a rigid central tube 304 provided with radial holes 341 , a cylinder 303 made of a porous, flexible, elastically deformable material, and an anti-adherent external sheath 305 covering the cylinder. The compacting roller further comprises a shielding sheath 307 interposed between the cylinder external surface 333 and the anti-adherent external sheath. This shielding sheath absorbs and/or reflects the heat radiation emitted by the heating system 9 such that the heat radiation does not reach the flexible material cylinder. The injected air, exiting from internal passage 342 of central tube 304 through radial holes 341 , traverses the entire cylinder so as to cool the shielding band and leaks by the cylinder lateral sides 336 .
Although the invention has been described in connection with particular embodiments, it is to be understood that it is in no way limited thereto and that it includes all the technical equivalents of the described means as well as the combinations thereof should these fall within the scope of the invention. In the described embodiment, the thermal regulation system is used to cool the flexible compacting roller. The thermal regulation system may understandably be used to heat the flexible compacting roller. | A fiber application machine for the production of parts made of composite materials comprising a compacting roller for applying on an application surface a band formed of at least a resin pre-impregnated flat fiber, and a heating system able to emit a heat radiation towards the band. The compacting roller comprises a rigid central tube provided with radial holes, and a cylinder made of an elastically deformable, flexible material, assembled on the central tube, and having a fluid communication assembly that brings the radial holes into fluid communication with the external surface of the cylinder. The machine includes a thermal regulation system that injects a thermal regulation fluid in the central tube internal passage. | 1 |
This application claims the benefit of provisional application No. 60/315,577 filed Aug. 28, 2001.
BACKGROUND OF THE INVENTION
Femoral neck fractures are a major source of morbidity and mortality in the elderly population. Ninety-eight percent of all hip fractures occur in people over the age of fifty, with the average age being seventy-nine for females and seventy-four for males. By age ninety, thirty-two percent of all females and seventeen percent of all males in the United States will have sustained a hip fracture. Hip fractures occur at a frequency of 9.6/1000 people—translating into 240,000 hip fractures per year in the U.S. alone. Due to the increase of the elderly population, the projected conservative estimates predict that by the year 2040, there will be 520,000 hip fractures per year. The risk of sustaining a second hip fracture is increased nine fold (from 1.6/1000 to 15/1000), and six fold in females (from 3.6/1000 to 22/1000).
Hip fractures are the number one cause of accidental death in the U.S. in the age group over 75. There is a twelve percent decrease in a person's life expectancy after sustaining a hip fracture with the greatest mortality occurring in the first four to six months. Between fourteen to thirty-six percent of all hip fracture patients die in the first year post injury. Only sixty-four percent of the patients return to the community and twenty percent will not regain the ability to ambulate without assistance.
Medical cost from hip fractures are a significant strain on our already over-taxed healthcare system.
The femoral neck poses a difficult problem to the elderly patient and the treating orthopedic surgeon. During the aging process, in general, endosteal and outer periosteal diameters increase as a protective mechanism. As the bone mass shifts further from the epicenter, skeletal strength is maximized despite a decrease in bone mass. However, similar protective mechanisms do not occur in areas of cancellous bone (i.e., the femoral neck). In addition, the femoral neck is deficient in periosteum and is, therefore, unable to compensate for loss of endosteal bone by periosteal bone formation. When an elderly patient falls, it is estimated that approximately 3700 kg-cm of energy must be dissipated. The femoral neck can only absorb approximately 60 kg-cm of energy prior to fracture. Most of the energy in a fall is absorbed by active muscle contractions. In an elderly patient, the neuromuscular response cannot act quickly enough to dissipate the kinetic energy. Consequently, when the level of stored energy in the neck exceeds its threshold, a fracture develops.
Treatment of femoral neck fractures is a challenge for orthopedists despite progress in practice and technology, particularly with osteoporotic bone. Femoral neck fractures are usually repaired using hip screws or an angled blade plate, both techniques requiring a metallic plate fixed to the lateral femur through cortical screws. Substantial surgery is associated with lateral places. The surgery usually stiffens the femur laterally but risks overloading the lateral femur. Either procedure may not provide enough stability at the fracture site in osteoporotic bone. These treatments are only used as post-fracture curatives. No standard procedure is performed to prevent femoral neck fractures, although Crockett in 1960 proposed pinning the femoral neck for prophylactic use.
A limited number of reports investigated prophylactic strengthening of an intact femoral neck. Beside medical measures, Crockett (1960) suggested pinning, using a pin of 4 mm, the femoral neck of high-risk patients. Pinning the femoral neck along the neck axis strengthens most effectively against shear stresses. Crockett supported his contention that pinning intact femora can effectively strengthen the femoral neck through experiments. In addition to the risk of shear fracture of the femoral neck, delamination between cortical (cortex of the bone) and cancellous bone remarkably reduces mechanical strength of the femoral neck composites (cortical and cancellous bone). The risk of delamination is highest at the interface of cancellous to cortical bone. Delamination risk can therefore be reduced if the interface and the supporting cancellous bone are strengthened.
Franz, et al. (February 2001) presented at the 47 th meeting of the Orthopaedic Research Society a study investigating the feasibility of injecting low-viscosity bone cement into the proximal femur and determining the corresponding augmentation effect. In their study, Franz, et al. drilled a 3.5 mm canal along the femoral neck axis. Bone cement was injected using a 4 mm biopsy needle. Although this study showed improved capacity of injected femora to withstand larger forces prior to fracture if compared to contra-lateral femora, there was a rise in temperature due to curing cement, and unpredictable long-term behavior of cements. These factors prevented current use of this technique as prophylactic measures for reducing fracture risk of the femoral neck. Although filling the proximal femur with bone cement can effectively reduce delamination fracture of the femoral neck, limited shear capacity of bone cement remains unpredictable for long-term use. Although the cement injection was monitored, there was no mechanism to control injection.
The above data clearly shows that a new effective and widely applicable strategy to prevent hip fracture is urgently needed. Medical treatment to prevent femoral neck fractures, as well as other fractures in the elderly have been geared with guarded effectivity to decreasing the rate of bone mass loss by either hormonal therapy (i.e., estrogen), by calcium supplementation, and by weight bearing exercises. Surgical treatment has been used solely as a post-fracture modality in the treatment of femoral neck fractures. To date, no surgical technique has been developed to prevent femoral neck fractures from developing.
References
1. Crockett, GS (1960). Osteoporosis in the Elderly. Clinical Practice.
2. Franz, T; Heini, PF; Frankhauser, C; Gasser, B (February, 2001). Reinforcement of the Osteoporotic Proximal Femur Using PMMA Bone Cement—An In Vitro Study. 47 th Orthopaedic Research Society. P. 0989, San Francisco, Calif.
SUMMARY OF THE INVENTION
An objective of this invention is to develop a method and apparatus of a femoral neck augmentation technique. The goal is to strengthen the femoral neck sufficiently to withstand a larger amount of force prior to fracture, utilizing a minimal invasion procedure. Traditional methods of surgical instrumentation are being used to fix the femoral neck fracture. Most of these methods require substantial surgical and anesthetic procedure. None of these methods can be used as a prophylactic method to augment the bone and prevent an impending fracture.
The proposed invention provides a new method of surgical prevention, by performing a minimal novel surgical procedure before a fracture occurs. Thereby, a bigger and more complicated procedure may be prevented.
The method includes percutaneous injection of uncured plastic material into the weakened femoral neck, before a fracture occurs. First, a hole is drilled into the femoral neck. The hole is filled with an uncured filler cement after loose materials have been removed from the hole. Then, an open-ended tube, an implant, having openings through its walls is inserted into the hole and attached to the bone. Finally, additional filler cement is provided under pressure to the inside of the tubular implant. The filler cement flows into spaces in the bone structure via the tube wall openings. Pressure is maintained until the filler cement has hardened.
Materials, which are currently used in surgery in the body, are used as the implant and cement for femoral neck augmentation. The filler cement has a degree of resilience and the capability of adhering to bone and the implant. The tubular implant and filler cement are less rigid than pins and screws, allowing the bone-cement construction to absorb energy prior to fracture.
The present invention relates to a cannulated implant that prophylactically strengthens an intact osteoporotic femoral neck which is at high risk of fracture. The cannulated implant is placed in the bone along the femoral neck axis and features outer surface openings, designed for extrusion there through of bone cement into femoral bone regions affected by osteoporosis. Bone cement penetrates into the femoral head, femoral neck and proximal femur. Implant and cement, penetrated into cancellous bone, strengthen the proximal femur and reduces risk of femoral neck fractures.
This invention is a hybrid technique (implant and cement) combining an implant and cement for prophylactic and/or preventative use, although the technique can be used as post-fracture curative and/or palliative procedure. Preventative effect of the new technique exists in that the implant, connected to cement penetrating adjacent cancellous bone, strengthens the femoral neck to withstand greater force prior to fracture. This technique requires no lateral plate, thus minimizing surgery and reducing lateral load shift. Cement extruded through the implant into cancellous bone intimately connects the implant with bone, stabilizing and strengthening the proximal femur prior to fracture. If fractures can be prevented there will be less hospital admissions and prorogated health care, benefiting both surgeons and patients.
The present invention introduces a new technique that strengthens against delamination as well as shear fractures. It combines (a) using a cannulated implant strengthening the femoral neck against shear fracture and (b) injection of plastic material, through the hollow implant with openings at the surface, into the femoral neck. The cement penetrates up to the neck cortex and strengthens against delamination fracture. This invention also features a method and apparatus that locally controls and directs cement extrusion into the surrounding bone.
Recent experimental results by the inventors support the convention of prophylactically strengthening the femoral neck prior to fracture. A strengthening factor up to 3 was measured when osteoporotic bone was strengthened. It is concluded from this study that this technique (implant and cement) is most effective when applied as a preventative measure to patients with a high degree of osteoporosis. This technique can also be used to stabilize femoral neck fractures.
Still further objects and advantages of the invention will be apparent from the specification.
The invention accordingly comprises the several steps and the relation of one or more of such steps with respect to each of the others, and the apparatus embodying features of construction, combinations of elements and arrangement of parts which are adapted to effect such steps, all as exemplified in the following detailed disclosure, and the scope of the invention will be indicated in the claims.
BRIEF DESCRIPTION OF THE DRAWINGS
For a fuller understanding of the invention, reference is had to the following description taken in connection with the accompanying drawings, in which:
FIG. 1 is a fragmentary semi-schematic view, partially in section, of the apparatus and represents an instant during the method in accordance with the invention for augmenting the femur with cement and an implant;
FIGS. 2 a-c are three orthogonal views of an implant in accordance the invention;
FIGS. 3 a-b is an alternative embodiment of a circular implant in accordance with the invention in elevation and diametric section;
FIGS. 4 a-d illustrate surface variations for medial portions of implants;
FIGS. 5 a-c illustrate variations for implant cross-sections;
FIGS. 6 a-c illustrate reinforcement elements for augmenting the femur in combination with a cement;
FIG. 7 is an alternative implant in accordance with the invention; and
FIG. 8 illustrates a femur augmented at two locations in accordance with the invention.
The figures are not drawn to scale.
DESCRIPTION OF PREFERRED EMBODIMENTS
With reference to FIG. 1, the femur 1 (thighbone) features a proximally rounded head 2 . The proximal femur 1 has a long shaft 4 . The femoral neck 3 connects to the femoral head 2 and shaft 4 . The femur 1 features a hard thin shaft cortex (shell) 5 a that is remarkably thicker than the cortex of the neck 5 b . The proximal femoral cortex is filled with spongy-like bone (cancellous bone) 6 . A line 9 connects the head center 7 to the center of the femoral neck 8 and is named the axis of the femoral neck. The projection of the line 9 to the lateral femur cortex is called the drilling starting point 10 .
The invention includes a hollow implant 20 and injection tube 40 . The implant 20 has two portions, a lateral portion 21 and a medial portion 22 , also called the implant shaft. The implant has a longitudinal continuous hole 23 through its lateral and medial portions. The injection tube 40 has an identical geometrical cross-section shape as compared to the profile of the implant hole 23 . The continuous hole 23 is circular; the injection tube 40 is also circular. The outer dimension 41 of the injection tube 40 is slightly smaller than the inner dimension 24 of the hole 23 to provide a tight but sliding fit as described more fully hereinafter. The injection tube 40 has thin wall thickness to maximize the tube inner dimensions. The larger the inner dimensions of the tube, the less pressure is required to extrude cement into cancellous bone. The lateral portion 21 of the implant 20 has a screw thread 26 along the length of the lateral portion to fix the lateral portion 21 into the femoral cortex 5 a . The implant 20 may feature a mechanical weakening; e.g., a circumferential groove (not shown for clarity in FIG. 1 but located at 27 ) between the medial and lateral portions 21 , 22 of the implant 20 . The weakening permits flexure and prevents transferring large bending moments to the lateral femur. The lateral portion 21 of the implant 20 includes a slot 58 that serves when connecting a screwdriver to insert and fix the lateral portion of the implant into the femoral cortex 5 a . The implant 20 has openings 60 through the tube wall on its lateral portion 21 (see FIG. 2) and medial portion 22 connecting to said continuous hole 23 of the implant. The openings 60 on the implant 20 are distributed circumferentially and longitudinally over the implant surface. The openings 60 at the lateral portion 21 of the implant 20 extend through the screw thread portion 26 .
In an alternative embodiment (FIGS. 3 a-b ) in accordance with the invention, the rectangular holes 60 in the lateral and medial portions of the implant 20 ′ are recessed in circular grooves 62 in the outer surface 28 of the implant shaft. The grooves 62 extend circumferentially between openings 60 and traverse adjacent openings 60 . The grooves may also extend longitudinally and diagonally between openings. A weakening groove 27 is located between the medial and lateral portions. The quantity of holes 60 at each longitudinal groove location is not limited to two (illustrated).
In an augmentation method of this invention:
(1) A continuous hole 14 (FIG. 1) of the same outer dimensions as the implant 20 is created along the femoral neck axis ( 9 ). The hole 14 , at its proximal/medial end 15 , does not reach the thin femoral head cortex ( 5 b ).
(2) The hole 14 is then flush-washed with saline solution to clean the hole of bone abrasions and fat tissue. In addition to flush washing, a sucking (vacuum) technique is used to further clean the hole 14 .
(3) Cement is prepared (3 to 4 commercial portions) and poured into a syringe (not shown) connected to the injection tube 40 through an adapter 16 . The hole 14 created along the femoral neck axis 9 in step (1) is next completely filled with cement.
(4) The implant 20 is then carefully placed into the hole 14 and cement. The medial portion 22 of the implant 20 slides into the hole 14 , while the lateral implant portion 21 is threaded into the bone.
(5) The injection tube 40 is next completely inserted in the hole 14 by sliding into the implant 20 until the injection tube tip 42 reaches to the medial end 15 of the hole 14 , 23 . Cement in the syringe and injection tube 40 is then pressurized by applying pressure on the syringe plunger. Cement is thereby pressed through the tube 40 and passes axially through the implant end 30 into the surrounding bone of the femoral head 2 , the cement flowing and distributing directionally from the injection tube tip 42 and implant 20 in accordance with the local levels of bone porosity.
The pressurized injection tube 40 is then pulled back gradually until its tip 42 approximately reaches the region of the femoral neck center 8 . There a large portion of cement is forced through the tube 40 , passes radially through the implant openings 60 on the implant 20 and penetrates into surrounding cancellous bone 6 of the femoral neck 3 , whereby the neck 3 is completely filled with cement.
To complete the filling procedure, the tube tip 42 is pulled back until it reaches the region 11 of the femoral axis 9 . Any cement left in the syringe is then completely extruded around the implant 20 into the surrounding cancellous bone.
(6) The cement is brought to its hardened state by means suited to the particular cement that is utilized.
(7) The distal end (exposed) of the implant 20 is trimmed of excess material, as may be required, and the original incision that provides access for forming the hole 14 of step (1) is closed for healing.
The openings 60 of the implant 20 and grooves 62 in conjunction with the injection tube 40 facilitate local pressurization and cement distribution at the bone/implant interface. The injection tube 40 is selectively positioned at the locations of the implant 20 where it is desired that the cement should be pressurized. The injection tube 40 has a large diameter (thin wall) continuous hole 44 so that controlled cement extrusion is achieved. The space between the outer dimensions of the injection tube 40 and the internal dimensions 24 of the implant 20 is large enough so that air escapes during cement injection, but small enough that the cement does not go back through this generally annular space.
When cement is extruded through the tube 40 and close to the openings 60 , cement penetrates into adjacent grooves 62 . Thereby the grooves 62 connected to openings 60 produce a local cylindrical area of cement around the implant shaft of homogeneous pressure. The area of homogenized pressure improves the area and depth of penetration of cement into the bone. In addition, the local pressurization facilitates controlled distribution of cement into the surrounding bone. The grooves 62 and openings 60 further strengthen the physical connection between the cement, implant, and infiltrated cancellous bone. The implant may feature a groove (not shown) close to its tip 30 . This groove is circular and cuts through adjacent openings 60 . The implant tip 30 may feature an extended thread (not shown) in addition to the groove.
The following remarks may in part be repetitious of the above, nevertheless they describe important features. FIG. 3 is similar to FIG. 2 but clearly indicates that irregularities may be formed on the outer surface of the implant, whether elevated above or penetrating the surface. These irregularities provide better adhesion for the cement with the implant and provide further holding engagement with the bony structure. As stated, cement distribution and penetration are enhanced.
The implant may be made of metal, for example, stainless steel, titanium, tantalum, nickel-cadmium and other metal alloys. The implant may be made of plastic and may even be made of the same material as the cement that is used for bone augmentation. On the other hand, an implant plastic may differ from the cement, and may be a composite material that is reinforced, for example, with rods, fibers, wires, whiskers, etc. as known in the plastic arts. The implant may be laminated of different materials. Ceramic materials that are altered in composition so as to have a degree of resiliency may also be used.
In both physical construction and in the material selection, the practitioner and manufacturer must be aware of the required non-toxic properties of the material. There must be no long time local toxicity. An opportunity for bony ingrowths into the insert is very desirable.
The cement material must have a suitable liquidity before curing so that it is readily injectable through the inlet opening into the hollow center of the implant. The plastic, elastic and mechanical qualities of the cement after curing must be considered. There must be minimal degradation with time of the performance characteristics of the implant and the cured cement. An ability to augment both the cement and the implant with fibers, whiskers, and the like, must be considered. The implant and the cement may each be combined with a material having a positive bone growth factor included. Detectability of the materials when exposed to x-ray or used in a CT scan or magnetic resonance imaging device, must also be considered.
Nevertheless, it must be noted that in spite of the many parameters which can differ based upon the patient and/or the preferences of the manufacturer and practitioner, the basic method steps and constructions in accordance with the invention remain applicable.
The sliding connection between the cement filled injector tube and the implant that is positioned within the bone must be leak tight to a degree that the cement can be pressurized and air can escape (with no or little leakage of cement at the connection) as cement is urged into the center of the implant. The cement passes through the axial and lateral flow openings of the implant to fill and engage cavities in the bone, and to fill the implant itself.
Many types of connection between the bone and the implant will be suitable. The connection is not limited to a particular type although in development testing of the present invention a threaded connection was found to provide favorable results in preventing leakage of cement and loss of pressure on the cement while filling and hardening the cement.
Although many materials may be used as cement, presently preferred is polymethylmethacrylate (PMMA), which was used with good results in development testing of the present invention. This material provides approximately 12 minutes of working time from a liquid state to a hardened cement after the elements to produce the cement have been mixed together. Pressure was maintained on the cement during the curing process in the bone cavity and insert.
It is understood that some materials that may serve as cement may expand on curing and other materials may be dimensionally stable or may contract. An expanding cement is preferred, as it will assist in penetrating the bony structure with cement.
When cement is first inserted into the drilled opening (hole) formed in the bone, before the implant is put in place, the cement is initially delivered at the proximal end (deepest into the bone) of the hole so that air may readily escape from the opening as well as bone chips, fatty materials, etc., that may remain. The cement injection tube is gradually withdrawn as the hole fills.
Making the implant of pre-stressed materials may be advantageous where the material is otherwise brittle in tension. Thus, similar to pre-stressed concrete, pre-tensioned reinforcement within the brittle material may permit use and give the material resilient load bearing qualities.
During practice of the method, the implant may be inserted with the distal end substantially externally flush with the bony structure so that the implant is in its final position, or the implant may be slightly extended from the bone surface to allow for convenient interface with the cement source. After the cement has set, the practitioner can physically modify any extending portions of the insert to suit his preference and the needs of the particular situation.
Round holes 60 are illustrated in implants in several figures (land 4 a ). An implant may have holes of any shape through its walls. Tabs or spurs of different shapes that are, for example, punched through the surface may also be used (FIG. 4 b ). Such features provide openings for flow of cement from the center of the implant to the bony structure, and also provide a good grip that resists removal of the implant once it has been inserted into the bony hole or socket that has been prepared for it.
FIG. 4 c illustrates that the implant need not be round in cross section. The best shapes will in time be determined from continued use of this method. However, it is expected that the patient's bone structure and the practitioner's preferences will in large measure determine the contours of the implant that is selected and inserted in the femur.
FIGS. 5 a-c show end views of implants to illustrate that they may be round or oval, and almost any imaginable shape that will fit within the contours of the bone. However, regardless of the shape of the implant's cross-section, the cross-section of the injection tube must be substantially congruent and provide the sliding fit that permits air to escape with a minimum of cement leakage or pressure loss. Such a fit may be provided based on filling procedures using a particular cement. Suitable clearance may be provided along the entire perimeter of the implant/insertion tube interface. On the other hand, a tight sliding fit may be locally relieved (not illustrated) for escape of air by longitudinal grooves, slots, flutes, etc. of small cross-section on one or both surfaces, while still minimizing escape of cement because of the greater viscosity of the cement (compared to air).
FIG. 4 d indicates an implant that threads itself into a hole provided in the bone so that the implant is not easily removed from the bone. This implant, like every other implant in accordance with the invention, will also have lateral openings through its surface.
The surfaces of all implants may be roughened, textured, porous, etc. for better engagement and integration in time with the bony tissues. Bone growth factors may be included in the surface or throughout the implant material (and in the cement).
FIGS. 6 a-c illustrate reinforcement means 17 inside the central hole 14 formed in the femur, which otherwise is filled with cement 18 that also penetrates the surrounding cancellous bone. After the cement has been injected in the hole 14 and cures, the reinforcement means becomes a permanent reinforcement for the cement.
The cement is selected for its viscosity, handling and setting time, and strength after curing (polymerization or precipitation, etc.). The cement changes from a liquid to a solid phase in an operating time frame based on various physical effects, e.g. temperature, heat. The cement 18 may be a bone or dental cement, polymer, elastomer, and absorbable and biodegradable materials, and may combine bone growth factors and other elements enhancing biocompatibility. The cement provides adhesion to bone tissue and to the reinforcement 17 . The cement may include particles, fibers, etc., improving the shear properties.
The reinforcement 17 is an elongated body, e.g., circular or elliptical rod, of any geometrical form featuring outer dimensions similar to the hole 14 . By inserting the elongated body 17 , the cement in the hole 14 is pressurized to fill radial spaces between the body 17 and surrounding bone. Pressurized cement also penetrates into adjacent cancellous bone when the elongated body 17 is inserted.
The reinforcement 17 is made from solid material(s), e.g., cement, metals, composites, fiberglass, cement reinforced with wires, composites of synthetic polymers, porous biodegradable materials, or moldable, hand-shapeable material suitable for strengthening the femoral neck.
The reinforcement 17 may be prefabricated from the same cement material as is used subsequently in flowable state to fill the hole 14 . The reinforcement intimately connects with surrounding cement by, e.g., grooves, keys, threads, roughened surface. A laminated elongated body made of layers may be used. Outer surfaces of the laminated, elongated body may have adhesive characteristics similar to the filling cement, whereby they connect to each other. A twisted wire is used in FIG. 6 c.
FIG. 7 illustrates another implant 50 in accordance with the invention where in the medial portion 51 fingers 52 extend from the mid-portion of the implant toward the proximal end 54 and provide a more flexible arrangement than those implants already illustrated. Each finger 52 extending toward the proximal end 54 is in effect a cantilever beam with a free end and each finger has good strength with flexibility. Additionally, the ability of the cement to readily flow into the bony structure is enhanced by this construction. The outer dimensions of the injector tube 40 also correspond with the inner dimensions of the lateral portion 53 and of the fingers 52 to provide a continuous tight sliding fit as required for filling the implant with cement. The lateral portion 53 includes through holes 60 and may also include surface grooves 62 .
FIG. 8 illustrates that more than one implant 20 may be inserted in respective holes 14 formed in the same joint 1 using the methods and apparatus of the present invention.
In development of the present invention, one of many favorable results was achieved using a circular cross-section biocompatible stainless steel implant having a length of 110 mm, an outside diameter of 12 mm where unthreaded and 14 mm where threaded. Thread pitch: 16 per inch. The medial portion ( 22 ) length: 70 mm; lateral portion ( 21 ) length: 40 mm. Inside diameter: 8 mm. Openings 60 were generally rectangular 3 mm×5 mm spaced longitudinally in nine circumferential bands.
The cement injection tube 40 was copper with clearance for sliding along the internal implant surface in the approximate range of 100 to 200 micrometers, assuming concentricity. Air was able to escape but not the cement. 40 to 50 ml of cement was injected in the experiments.
It is presumed that implants would, in time, be provided by a manufacturer in a kit also including a properly mating injection tube that assures a pressurizing sliding seal. Various lengths, diameters, cross-sections, materials, etc., would be available in a kit of elements.
It will thus be seen that the objects set forth above, among those made apparent from the preceding description, are efficiently attained and, since certain changes may be made in carrying out the above method and in the constructions set forth without departing from the spirit and scope of the invention, it is intended that all matter contained in the above description and shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.
It is also to be understood that the following claims are intended to cover all of the generic and specific features of the invention herein described, and all statements of the scope of the invention which, as a matter of language, might be said to fall therebetween. | Combining an implant and cement for prophylactic and/or preventative use for femoral neck augmention. A hole is drilled into the femoral neck. The hole is filled with an uncured filler cement after loose materials have been removed from the hole. Then, an open-ended tube, an implant, having openings through its walls is inserted into the hole and attached to the bone. Finally, additional filler cement is provided under pressure to the inside of the tubular implant. The filler cement flows into spaces in the bone structure via the tube wall openings. A sliding leak-tight fit between the implant and a cement injection tube permits delivery of cement at preselected locations along the implant length. Pressure is maintained until the filler cement has hardened. A strengthening factor up to 3 was measured when osteoporotic bone was strengthened. | 0 |
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The invention relates to golfing. In particular, the invention relates to a device for analyzing and developing skills of a player. The invention also concerns a method for analyzing the performance of the player during training or playing.
[0003] 2. Description of Related Art
[0004] Golf is based on one's ability to predict the trajectory of a ball in response to a certain combination of swing and club. Swings of golfers are traditionally analyzed either by naked eye during the hit or by recording the swings using video equipment and analyzing them afterwards. In both cases, for a proper analysis of the pros and cons of the swing, a professional golf trainer is usually needed. Naked-eye and video-based evaluation of swings suits well for discerning major faults in, for example, the stance and alignment of the golfer and the movement of the body of the golfer during the swing. The results of such evaluation are also highly subjective and reflect the view of the person watching the swing, typically a golf trainer. For a golf trainee, it may be frustrating if several professional have different, probably opposing, views of the pros and cons of his or her shots. What is difficult to exactly evaluate by visual observation of the golfer, is the temporal progression of the swing and especially the similarity of two or more swings. In addition, hiring of a personal trainer having a suitable video equipment is very expensive, and the video equipment is difficult to carry.
[0005] U.S. Pat. No. 6,648,769 discloses a swing analyzing system comprising an instrumented golf club including a plurality of sensors, an internal power supply, an angular rate sensor and an internal ring buffer memory for capturing data relating to a golf swing. The swings are analyzed one-by-one for assisting a golfer's swing, or for designing an appropriate golf club for a specific type of golfer.
[0006] U.S. Pat. No. 6,073,086 discloses a device for measuring the speed of swing of a movable object, such as a baseball bat or golf club. Part of the device is embedded, secured, or attached to the projectile or movable object of interest, and consists of an acceleration sensor, threshold circuit, and a radio transmitter.
[0007] In U.S. Pat. No. 5,688,183 a velocity monitoring system for golf clubs is described. The monitor is preferably detachably securable to the golfer's hands or a golf glove. An inferential determination of club head velocity may be made by using an accelerometer disposed in the monitor.
[0008] U.S. Pat. No. 5,233,544 describes a swing analyzing device comprising swing practice equipment such as a golf club having acceleration sensors attached all over the club for analyzing the movements of the club with good precision during a swing.
[0009] U.S. Pat. No. 4,991,850 discloses a golf swing evaluation system including a golf club containing a sensor and an associated display for indicating the force and location of the impact of the club head against a golf ball.
[0010] The prior art devices make mostly use of acceleration sensors disposed in the golf club. However, such solutions usually change the properties of the club, whereby the measurement results may be unreliable. Moreover, in the above-mentioned devices, the analysis is based on monitoring swings one-by-one. They are well suited for practicing or improving technicalities of the swing. In monitoring the swing as a whole, or increasing or analyzing the attained muscle memory needed in golf, the present solutions are more unfavorable. Golf swing is a pendulum motion, not just hitting a ball with a club. A good swing is a combination of many factors, such as a right stance of the player, good balance throughout the swing, correct spatial course of the club and feasible temporal development of the swing. In order to reduce the number of shots required, the swing of the golfer has to be very constant and regular. If one or some of the preceding factors, for example, are irregular, the whole swing, and ultimately the flight path of the ball becomes unpredictable.
[0011] There are no known devices or methods which can be used for automatically and objectively analyzing the swing of a golfer in order to assist the golfer to improve his or her skills as a golf player.
SUMMARY OF THE INVENTION
[0012] It is an aim of the invention to achieve a novel device for helping sportsmen improve their skills by providing information on the repeatability of a motor act, especially a two-phase act such as a golf swing, that is frequently needed in the sport they go in for.
[0013] In particular, it is an aim of the invention to achieve a novel device and method for helping a golfer improve his or her skills by providing information on the repeatability of the swing of the golfer.
[0014] It is also an aim of the invention to achieve a novel method for determining the repeatability of a swing of a golfer using data collected during various swings.
[0015] It is a further aim of the invention to achieve a device that assists a golfer to focus his or her training on a specific part of the swing.
[0016] It is also an aim of the invention to provide a device and method, which can be used for obtaining objective information on the courses of swings.
[0017] The device according to the invention comprises means for collecting data on courses of repeatedly performed motor acts in response to body movements of the sportsman. In addition, the device comprises means for calculating at least one characteristic number based on the data collected during the motor acts. The means for collecting data comprise at least one sensor capable of delivering information (output signal) on the body movements of the sportsman during the motor acts and a signal processing unit for refining the information delivered by the sensor. The characteristic number represents, for example, repeatability of the different parts of the swing of the sportsman, i.e., how similar the various repetitions of the motor act are to each other in terms of the parameters measured.
[0018] The method according to the invention comprises monitoring the performance of a sportsman by collecting data on the course of a plurality of motor acts performed by the sportsman. Body movements of the sportsman are is sensed by an applicable sensor. The information provided by the sensor is then refined and used for calculating at least one characteristic number representing the repeatability of the motor act.
[0019] The motor act can be, for example, a swing performed by a golfer.
[0020] The data extracted from the sensor output signal can, for example, be used to describe one, some or all of the following swing properties: the tempo of the swing, the rhythm of the swing, the duration of the backswing and the velocity of the blade of the club during downswing. In this context, the tempo of the swing stands for the total duration of the swing, i.e., the time period from the beginning of the backswing to the completion of the swing. By the rhythm of the swing is meant the temporal proportions of the back- and downswing of the whole swing. The duration of the backswing is the time period from the beginning of the swing to the turning of the swing in the upper position of the club. In estimating the velocity of the club blade during downswing, pre-stored data on the length of the club can be used. When calculating the characteristic number(s), the mean values and standard deviations, for example, of the parameters measured can be used.
[0021] After several swings, the characteristic number(s) can be calculated from the measured parameters of each of the swings. Typically this step comprises calculating the coefficients of variation, and/or other applicable statistical quantities, of the swing properties for obtaining an objective criteria on the variability of the properties, and thus the repeatability of the swing parts the parameters represent. The step can also comprise calculating a weighed sum of some or all of the coefficients of variation for obtaining a characteristic number, which represents the overall repeatability of the swing in terms of several properties at once. In this document, this kind of weighed-sum characteristic number is also called a swing index number (SIN).
[0022] Considerable advantages are achieved by the present invention. A basic challenge in many sports, especially golfing, is that the temporal and spatial course of swing varies a lot from hit to hit. This causes the accuracy of the hits to decrease. In other words, the accuracy of the hits is highly dependent on the reproducibility of the swings. We have found that a reliable analysis of swings can be carried out automatically by a suitable electronic device, which can be mounted on the body or club of the sportsman. The variability of the swings can be detected by measuring certain parameters during the swings. The parameters can be used for pointing out the potential weaknesses and faults of a golfer by calculating various characteristic numbers, which represent different sectors of the swing or the swing as a whole.
[0023] In particular, we have found that determination of the key points of time of a plurality of swings is a good tool for identifying the weaknesses of the swing. This is because for example an unbalanced stance or irregular movement of the body of the golfer reflects in temporal variations. We have found also, that at least one acceleration sensor can be used for detecting the necessary key points reliably in order to make further analysis of the swing.
[0024] Advancing golfers change their way of swinging, the grip on the club or the set of clubs every now and then. These changes often involve also some changes in the temporal course of the swing. By using the device according to an embodiment of the present invention, golfers can track these temporal changes to see which parts of the swing are getting better (more constant) and which parts should still be improved. For example, the tempo of the swing can be well maintained constant in a new swing the golfer has practiced, but the duration of the backswing can deviate more than in his old swing.
[0025] The device according to an embodiment of the invention can be manufactured light, for example, to be carried on a wrist of the player. The player may start and stop monitoring of his or her swings whenever he or she wants. The device can be used during training, for example, on a driving of chipping range, but also during playing, for example, to monitor the similarity of several drives on teeing grounds.
[0026] The determined characteristic numbers of the swing of a player have been found to correlate well with the handicap (hcp) of the player. However, the index number describes the swing of the player more exactly, because the hcp is calculated by the overall performance of a player, including also the “swingless” areas of the game, such as mental and environment-dependent aspects of the game and putting. Hence, the characteristic number, especially the swing index number, determined by means of the invention, is a reliable measure of the hitting skills of a golfer.
[0027] According to one embodiment, the device informs the player which sector or sectors of the swing should be improved in order to make the swing more repeatable. This can happen by, after a predetermined number of swings, displaying several characteristic numbers representing different properties of the swing, to the user. This enables the player to concentrate his training on the weakest sector of the swing in order to enhance his or her skills towards more accurate shots. Alternatively or additionally, a swing index number representing the reproducibility of the swing as a whole can be displayed. In addition to displaying the results, there may be implemented also some advanced features in the device. The device can, for example, detect that the duration of the backswing fluctuates unacceptably much with respect to the fluctuations in the duration of the downswing and advice the player to concentrate on clean backswings in further training, or vice versa.
[0028] As is appreciated by a person skilled in the art, the device and method disclosed in this document can be used also for evaluating the shots and serves in other sports, such as tennis and baseball. In particular, the present solutions can be utilized in all kinds of sports making use of clubs, bats, sticks, racquets or mallets. In addition, the principles of the invention are applicable, for example, in ball games that require good body coordination and reproducibility of certain moves, such as basketball and boxing. For example in basketball, the reproducibility of free throws can be analyzed, and in boxing, the characteristics of the stretches and hooks can be analyzed.
[0029] In this description, golf terms such as backswing and downswing are used for describing the phases of the movement (motor act) in question of the sportsman. A person skilled in the art easily finds equivalent phases in many other sports. For example, when serves and hits of tennis are concerned, the backswing and downswing are easily distinguishable. In basketball, the equivalent phases are the small backpull of the player with a ball in his hands in front of his face and the stretching of hands when launching the ball towards the basket. As is the case in golf, also in basketball, the success of the throw is dependent on the ability of producing an exactly identical series of motion.
[0030] In many cases, the term “backswing” can thus be replaced with one of the terms “first phase of motor act”, “preparatory step of effort” or “the step of collecting potential for a forthcoming effort”. Respectively, the term “downswing” can usually be replaced with a term “second phase of motor act”, “step of effort” or “the step of releasing the collected potential for performing an effort”.
[0031] As is evident from the preceding disclosure and the description and claims hereafter, the term “swing” is used both in the meaning of a single swing and in a broader meaning describing the general hitting performance of a golfer (as in “repeatability of swing”).
[0032] The term “course of swing/club” is used for describing the temporal course of the swing/club, including all time-related measurable quantities, such as acceleration, velocity and the spatial information on the device, on the golfer, or on the club in time. By the term “repeatability” or “reproducibility”, we mean the similarity of at least two swings as regards to the courses of the swings.
[0033] Next, the invention will be examined more closely with the aid of a detailed description and with reference to the attached drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0034] FIGS. 1 a to 1 d depict four different phases of golf swing as a series of images,
[0035] FIG. 2 shows a flow chart describing the progress of the method according to one embodiment,
[0036] FIG. 3 shows an alternative flow chart describing the progress of the method according to another embodiment, and
[0037] FIG. 4 shows a schematic view of the components of the device according to a preferred embodiment.
[0038] FIG. 5 shows a graph of predicted handicap values with relation to actual handicap values of 32 players.
DETAILED DESCRIPTION OF THE INVENTION
[0039] In determining the preferred properties of a swing (tempo, rhythm, duration of backswing, velocity of club blade), measuring of three different time points (also called “key points”) is needed. Referring to FIGS. 1 a to 1 d , these time points comprise the time point when the hitter first moves the club from the starting position in order to perform the backswing ( FIG. 1 a ), the time point when the hitter changes the direction of the swing when the club is in an upper position ( FIG. 1 b ), and the time point when the swing is complete. This can mean either the time point when the club actually hits the ball (a little before the situation shown in FIG. 1 c ) or the time point when the downswing is fully finished off after the follow-through, once again in an upper position ( FIG. 1 d ). In a preferred embodiment, the key points are determined using the data obtained from at least one acceleration sensor embedded in the device, preferably a 3D acceleration sensor or three different sensors arranged to provide information on the spatial movement of the sensors. In addition to the mentioned time points, also other parameters, such pure acceleration data or data derived from the accelerations in different phases of the swing, can be used.
[0040] In FIG. 2 , the determination of characteristic numbers according to a preferred embodiment is illustrated by means of a flow chart. The chart and the following description on the progress of the monitoring program are only exemplary. It is appreciated by a person skilled in the art that the same or comparable results can be achieved by a number of different processes which do not deviate from the basic concept of the present invention.
[0041] The numerals in the FIG. 2 refer to following process steps:
[0042] 21 . Start the monitoring program
[0043] 22 . Detect the key points of a swing store predefined swing data
[0044] 23 . Check if a predetermined number of swings has been performed:
No: go back to step 22 , Yes: continue to step 24
[0046] 24 . Calculate coefficients of variation of predetermined properties of the swing
[0047] 25 . Calculate a weighed sum of the coefficients of variation calculated in step 14
[0048] 26 . Display results
[0049] 27 . End process
[0050] Starting of the monitoring program 21 is preferably done in response to user input. After starting, the device begins observing the movements of the player. In a preferred embodiment, the device includes a G-sensor or a set of G-sensors, which continuously provide data on the spatial movements of the device.
[0051] Swing detection in step 22 is preferably done using the acceleration data provided by the G-sensor(s). The device preferably detects and records the absolute or relative time points of the starting of the backswing (t a,1 ), the reversal of the swing in the upper position of the club (t a.2 ) and either the hitting of the ball or the ending of the follow-through after the downswing (t a,3 ). In this document, these time points are denoted t a,b , where a is the ordinal number of the swing and b is the ordinal number of the time point. The desired properties of the swing, for example, the tempo (p a,1 ) and rhythm (p a,2 ) of the swing, the duration of the backswing (p a,3 ) and the velocity of the club head (p a,4 ), can be calculated using the recorded time points in this step or in a later step (for example, step 24 ). In this document, the properties determined are denoted p a,c , where a is the ordinal number of the swing and c is the ordinal number of the property. In this example, the number of properties (C) is 4, but it can also be more or less than that. The data can be temporarily stored in a built-in or portable memory of the device. Some embodiments concerning the practical implementation of the detection step are described more closely later in this document with reference to FIG. 4 .
[0052] In step 23 , the device decides, whether it has successfully detected and recorded a predefined number of swings (A) in order to calculate the characteristic number(s). The predefined number of swings is preferably 2-100, typically 5-20. The number may be given by the user or it may be preset into the memory of the device. In principle, the higher number of swings, the more statistically reliable the results are. In practice, however, the tiring and enervation of the player after a large number of similar shots may cause additional fluctuations to the measured swing parameters, whereupon the optimal number of swings can actually be quite low. It has been found, that by using the embodiments described in this document, even after a set of 10 swings, there is usually enough data to evaluate the hitting skills of a player with good accuracy.
[0053] In step 24 , the mean values μ c , and standard deviations or are determined from the data set p a,c . From the means and deviations, the coefficients of variation CV c of the selected swing properties are calculated to form characteristic numbers SC describing the reproducibility of the sub-parts c of the swing.
[0054] In an optional step 25 , at least some of the quantities calculated in step 24 are weighed with weighing factors w c and summed to form a swing index number S. Thus, the swing index number S can be calculated as:
S = ∑ c = 1 C w c S c . ( 1 )
[0055] The weighing factors w c can be chosen to take into account the importance of each of the sub-parts c in formation a successful swing. The weighing factors can also be chosen such that S represents the estimated hcp of the player. It is also possible to use a special weighing function(s) ƒ c (S c ) and/or ƒ(S) in order to obtain results better corresponding to the real hcp of the player.
[0056] In step 26 , the results of the monitoring program are displayed to the user on the display of the device. The display can comprise an LCD or TTT unit, for example. The characteristic number(s), i.e., the coefficients of variation CV c and/or the swing index number S can be displayed as pure numbers, for example, in percentages, and/or in a refined form, for example, graphically. In a further embodiment, the swing index number S in given hcp-units. Thus, the results can be displayed in the following way, for example:
Tempo: 5.5% Rhythm: 19.4% Length: 5.4% Speed: 4.4% SIN: 8.3% (hcp 23.6)
[0062] In FIG. 3 an alternative flow of the process is shown. In this version, the calculation is performed similarly to the calculation described above, but the results are shown to the user after every swing (except the first one). The reference numeral 31 corresponds to the numeral 21 in FIG. 2 etc.
[0063] Because coefficients of variation are calculated using statistical deviations, they are comparable despite the number of swings performed or the club used. The same applies to swing index numbers calculated from the coefficients.
[0064] In a further embodiment the user is also provided with absolute values of the properties determined. For example, the absolute the velocity of the club blade can be an interesting quantity when practicing long drives. Information can be provided on each swing individually or averaged over several swings.
[0065] Referring to FIG. 4 , the device 40 preferably comprises a power source 44 , a timer unit 45 , a sensor 46 , a microprocessor 41 , a memory unit 42 and a display unit 43 . The devices is preferably driven by software 47 and also operated through a software-based user interface. Further, there may be means for transferring data to other devices, such as computers, by wire or wireless communication. In addition, the device can comprise other features commonly seen in wristop computers, such as climate sensors, a compass, an altitude meter or a GPS-locator. These features may also be utilized to provide additional useful information that can be used in advanced analysis of the skills of a golfer, for example, the variability of the swing in relation to prevailing weather conditions, or his moves on a golf course.
[0066] The sensor 46 comprises preferably an acceleration sensor (also “G-sensor”) or a plurality of acceleration sensors, which provide electrical signal proportional to the acceleration of the device. Such sensors can be manufactured as separate microchips, as a part of another component, or embedded in the wiring board or casing of the device. The G-sensor used can be responsive to acceleration in all spatial directions (i.e. a 3D G-sensor) or there can be arranged several (typically three) sensors sensitive to different, for example, orthogonal directions of movement. Different types of G-sensors that can be used are, for example, those based on capacitive coupling and piezoelectric effect.
[0067] The sensor or sensors 46 can me arranged to provide a plurality of signals for each direction separately (vector acceleration) or a total acceleration signal (scalar sum). In order to provide accurate information on the movements of the club, the sensor is preferably mounted on an essentially fixed location with respect to at least one part of the club. In a preferred embodiment, the sensor is an integral part of the main device, for example, a wrist watch or wristop computer, whereby the sensors follow the motion of the club precisely enough to provide sufficient data on the swing. However, we do not exclude such embodiments, which utilize at least one external sensor installed, for example, on the blade of the club and communicating with the main device by wire or wirelessly.
[0068] In addition to or instead of a G-sensor, a sensor or a set of sensors of some other type can be used. For example, position, velocity, alignment or proximity sensors can be used to provide additional data for determining, or information that is sufficient for determining, the key points of the swing. This may, however, require positioning some sensor elements separately from the main device, for example, on hitting ground, ball or a body of the golfer.
[0069] The detection of the key points of the swing is performed using the output signal(s) of the sensor(s) 46 . The signals can be in analogue or digital form. The detection process can also be implemented by analogue or digital means. If digital signal processing is utilized, analogue signals can be A/D-converted by suitable electronics before further analysis. The microprocessor 41 of the device is preferably used for digital signal processing. The acceleration data can also be calibrated, filtered and/or scaled before further analysis. If several sensors or sensor channels are used, arithmetic or algebraic operations can be carried out for forming derived data, such as sum signals or vector projections, e.g. for finding radial and tangential components, of acceleration data.
[0070] The detection can made in real time as the swing proceeds, in delayed real time, or after the swing has ended by analyzing stored signal data. In a preferred embodiment, the detection is carried out such, that when a key point of a swing is detected, its point of time is “stamped”. That is, the point of time is stored in the memory of the device as an absolute value or as a relative value with respect to some other time point. In a preferred embodiment, the detection is primarily based on monitoring the value, first derivative and statistical variation of the total acceleration. Also secondary characteristics, such as properties of different acceleration components can be monitored.
[0071] There may be implemented several instructions for carrying out the detection of the key points. Examples of such instructions are given in the following list:
Start of the swing: total acceleration is fairly constant (usually near the value 1 G, in most cases 0.5-1.5 G (G=gravity unit ≈9.81 m/s 2 )). Start of the swing: the standard deviation of the acceleration data is low. Start of the swing: right before starting of the swing, total acceleration is essentially zero (the club is held motionless near the ball, probably resting on the hitting ground, as the player concentrates). Turning of the swing: radial acceleration begins to change after a period of constant acceleration. Turning of the swing: the direction (sign) of tangential acceleration changes. End of the swing: the total acceleration changes strongly during a short period of time (the club hits the ball and the linear momentum of the club decreases due to the impulse).
[0078] The above-listed instructions (and other such instructions) can be logically combined for enhancing the detection. For example, the start of the swing has been detected with good probability if two or three of the first listed requirements are met. On the other hand, the ending of the swing can only have happened if the swing has started and turned. By means of the detection process disclosed above, it is possible to implement a swing monitoring program that does not need any input from the user during the monitoring session. However, there can be also implemented interactive monitoring programs or semi-interactive monitoring programs. In an exemplary semi-interactive program the device informs the golfer by a sound signal when it is ready for a new swing after it has detected that the player is in starting stance (i.e., when the device has been essentially motionless for a while).
[0079] The swing detection system can also utilize higher level artificial intelligence, such as fuzzy logic or learning systems, which adapt to a certain style of swinging and thus provide more reliable results. Detection can also be implemented by storing swing data temporarily and comparing the data with a pre-recorded reference swing acceleration profile or profiles in order to find similarities between them and to detect the key points that way.
[0080] In one embodiment, the signal given by the sensor can also be stored for further analysis by the device or by external data processing means, such as a computer. By this embodiment, the swings of the golfer can be analyzed thoroughly and/or developing of the swing of a golfer can be monitored in the long run in detail.
[0081] A timer unit 45 is used for obtaining correct time stamps for the key points of a swing. A timer unit can comprise a timer used commonly for performing typical timing functions of wrist watches, for example.
[0082] The memory unit 42 may be comprised of built-in memory, portable memory, or both. The microprocessor 41 can be programmed to handle the signal processing needed in determining the key points of the swing and the calculations needed in determining the characteristic numbers. Alternatively, all or some of the processing and calculations can be performed using specialized electronic components, such as microchips. The raw of refined (extracted) data on the individual swings can also be transferred to separate data processing means, such as a computer, for calculation of the characteristic number(s).
[0083] In a preferred embodiment, all the steps needed for determining and reporting the characteristic number(s) are carried out in a single device. The device can be manufactured light and implemented as a wrist watch or wristop computer.
EXAMPLE 1
[0084] A test set of 10 wings of 12 different golfers was performed in order to illustrate the capabilities of the present device and method. Two swing properties were chosen to be monitored, namely the duration of the backswing (property 1) and the duration of the downswing (property 2). Table 1 shows the mean values (μ) and standard deviations (σ) of the results. Also the handicaps of the golfers are shown.
TABLE 1 Hcp's and mean values and standard deviations of two swing parameters of 12 testees performing 10 swings. Test Person μ 1 σ 1 μ 2 σ 2 Hcp 1 0.5860 0.041150 0.2200 0.009428 12.0 2 0.7200 0.023094 0.2900 0.010541 10.0 3 0.7340 0.016465 0.2500 0.010541 10.0 4 1.1360 0.020656 0.3420 0.014757 3.0 5 0.6920 0.013984 0.2760 0.008433 26.0 6 0.9740 0.037771 0.3620 0.006325 21.0 7 0.9230 0.029367 0.3017 0.005376 0.0 8 0.6004 0.017500 0.2472 0.017041 1.3 9 1.0668 0.070290 0.3445 0.014378 26.0 10 0.7504 0.066890 0.2472 0.017041 13.0 11 0.8445 0.021083 0.3835 0.017393 26.0 12 1.6221 0.115028 0.3934 0.013914 10.0
[0085] A classification matrix based on the data on Table 1 is shown in Table 2. A classification function was used to classify the test persons into two groups based on their swing index numbers calculated from σ 1 and σ 2 . The groups consisted of those having a hcp between 0 and 10 and of those having a hcp more than 10. The results show, that only one test person was classified into a wrong group with the classification function used. Thus, the proportion of correct observations in this case is about 92%, the error rate being about 8%.
TABLE 2 Swing index and hcp classification matrix. 0 ≦ hcp ≦ 10 hcp > 10 (classified) (classified) 0 ≦ hcp ≦ 10 5 1 (real) hcp > 10 0 6 (real)
[0086] The experimental results disclosed is this example illustrate the potential of the invention. It should be noticed that despite the low number of swings, namely 10, and only two parameters of interest used in the experiment, the derived swing index values correlate well with the hcp values of the players.
EXAMPLE 2
[0087] FIG. 5 shows a graph of predicted handicap values with relation to official handicap values of 32 players. The official hcp is shown on the horizontal axis and the hcp-scaled swing index number obtained from a device (forecast) is shown on the vertical axis. Each of the players were asked to perform six as similar swings as possible. The swing index number was obtained with a wristop device using the principles described in this document.
[0088] The average predicted hcp of the players was 28 (st. dev. 20), the average actual hcp being 25 (st. dev. 16). The correlation factor between the predicted and actual hcp values was 0. 8. The correlation can be considered really high, taking into account that the number of repetition was only six. | The invention relates to a portable device and a method for monitoring the performance a sportsman performing a plurality of motor acts, such as golf swings. The device comprises at least one sensor providing an output signal, the sensor being responsive to body movements of the sportsman. A signal processing unit is used for extracting data on the course of each of the plurality of motor acts from the sensor output signal, and a computing unit is used for determining, based on the data on the course of the plurality of motor acts, at least one characteristic number describing the repeatability of the motor act. By the means of the invention, the handicap number of the golfer can be predicted with good accuracy by monitoring several his or her subsequent swings. | 0 |
This is a continuation-in-part of my U.S. patent application Ser. No. 07/831,518 filed Feb. 5, 1992, abandoned.
BACKGROUND OF THE INVENTION
This invention relates primarily to a method and article or device for protecting a user's fingers from abrasion and paper cuts when folding and creasing paper. A common example of use is creasing a letter-sized sheet or multiple sheets into three sections to enable enclosure in a business envelope for mailing. It may also be used for forming a crease line in a sheet of paper to enable tearing or slitting along the crease line or in the Japanese folding art of origami.
When creasing a sheet in the customary manner, one known technique is to start by first doubling over a section of the sheet along one edge, pinching the starting point of the crease between one's fingers and then drawing or pulling the compressed fingertips along the line to be creased. Another known technique is to place the doubled-over sheet on a solid surface, press a finger or thumb against the paper and move either the paper or hand to make the crease. While either one of these approaches works well for a few operations, the fingers are subject to abrasion if repetitive creasing tasks are performed. Many paper stocks are coated with substances which can be very abrasive to the skin if the skin is constantly run across the paper. Additionally, paper cuts are always a risk when creasing if the user is not careful.
Creasing can also be done by using one's fingernails on both sides of a sheet, or on one side against an opposing finger. In doing either of these, however, it is often necessary to first form a fold by finger pressing along the full length of the line to be creased to assure that the crease line will not stray, then returning to the starting point of the crease, pinching the fold line between the fingernails and drawing the nails across the prefolded line. Not only does this require two passes to create a crease, it also runs some risk of snagging and damaging the paper, because of the minimal area of fingernail contact with the paper at the pressure point. The risk of a paper cut occurring is greater when creasing with fingernails rather than pressing one's fingertips together. While skin damage from a paper cut is often very slight, it can be very painful, particularly if the cut occurs beneath a fingernail.
SUMMARY OF THE INVENTION
The method and device of my invention serve to provide a manually-produced accurate, controllable-pressure crease in a single pass across the sheet, without resulting in abrasion to the person's fingertips. It comprises a pair of arms, preferably slightly flexible, connected together at a hinged portion. The arms ideally fit between the pressure points of one's thumb and forefinger when a crease is made. At least one of the arms is provided with means for preventing the fingers from slipping from the device as it is drawn along the line to be creased. Such means can take any of several different forms and can be held between a pair of fingers during the creasing action or merely be attached to one finger.
In its preferred form, the creaser also incorporates a letter opener feature for slitting open envelopes and a paper combing feature for separating individual paper sheets from the top of a pile. The creaser has arms which are V-shaped outwardly from a hinge formed at the vertex of the V. The arms are preferably naturally biased apart to permit easy placement of the V over the starting point of the crease. The arms are then pressed together by the fingers, most handily and advantageously between the thumb and forefinger, and the fingers are then drawn along the line to be creased. In one form, the device may be made of a thermosetting plastic with a living hinge at the vertex of the V. The arms are preferably of equal length so the device can be made to stand upright as an inverted V on a desk, ready to be picked up and the device immediately used as taken. A logo or advertising message may be produced on the arms and be readily viewed from either side when the device is standing upright.
The principal object of the invention is to provide a manually-operable paper folder and creaser which minimizes the effects of paper abrasion and paper cuts to the fingertips of the person performing the creasing.
An important object of the invention is to provide a method of forming a controllable-pressure crease utilizing the creaser of the foregoing object, particularly to enable obtaining either a sharp or gentle crease, regardless of the number of sheets being creased.
Another object is to provide such a creasing device with a gripping means for resisting or preventing slippage of one's fingers from the device while performing a creasing function.
A further object is to provide such a device which can be used for folding and creasing with the device held in either the right or left hand.
Still another object is to provide an efficient means for simultaneously creasing a plurality of sheets with ease and accuracy.
A further object is to provide a creasing device which improves the capability of creasing a sheet of paper for use as a tear line, and which is capable of providing a finer tear line than when using conventional finger creasing techniques.
Yet another object is to provide a creasing device which is capable of easily carrying an advertising message or logo, whereby the device can be used as a promotional item for products with which the creaser is associated.
Another object is to provide such a device which can be made to stand on a desk of other surface, ready to be used in the position in which it is picked up.
A further object is to combine portions of the creasing article of the invention with means capable of performing other functions, such as slitting open envelopes or combing individual sheets from the top of a pile, all while the article is held in the same manner regardless of which task is being performed.
Other objects will become apparent from the following description in which reference is made to the accompanying drawings.
IN THE DRAWINGS
FIG. 1 is a pictorial depiction of a preferred form of my creaser being drawn along a line to be creased by a user's hand while the paper is held between a person's thumb and forefinger of the other hand.
FIG. 2 is a side view of the preferred form of my invention, illustrating the manner in which the creaser is grasped while it is standing upright on a horizontal surface.
FIG. 3 is a top view of the combined creaser/slitter/comb of FIG. 2 taken looking essentially in the direction of the arrow 3 of FIG. 2.
FIG. 4 illustrates the device of FIGS. 2 and 3 as it is held and used for slitting open an envelope.
FIG. 5 is a view of the device performing a combing function on a pile of sheets by pushing the device away from the user.
FIG. 6 is a fragmentary view of the device performing a combing function on a pile of sheets by drawing the device toward the user.
FIG. 7 is a view of a modified form of the combined creaser/slitter/comb looking substantially in the same direction as in FIG. 3.
FIG. 8 illustrates one simplified form of creaser as produced from a flat sheet of plastic or heavy paperboard and printed with a logo on any or all of several outwardly-facing sides.
FIG. 9 illustrates still another modification of the creaser looking substantially in the same direction as in FIG. 3.
FIG. 10 is a cross-sectional view of the device of FIG. 9 and is taken looking in the direction of lines 10--10, illustrating how the creaser performs on multiple sheets of paper.
DETAILED DESCRIPTION
A sheet of paper 10 to be creased has a doubled-over flap 12 of a preselected width pinched between a person's left thumb and forefinger to hold the paper. As is customary, the right thumb and forefinger also pinch the starting point S of a line 18 to be creased and then are drawn away from an edge 14 of the sheet to create the crease. Let it be understood that the word "fingers" are used generically herein to encompass any five fingers of a hand, including a thumb. This is necessitated due to the fact that it is possible to employ the device of my invention with fingers other than a thumb, although the desired controllable creasing pressure is believed best developed between a thumb and forefinger. It should also be understood that the crease line 18 can be formed either right or left handed according to the person's inclination and preference. Several illustrated versions of the device may be used with either hand. Those that cannot be used ambidextrously can be manufactured for use by either a right-handed or left-handed person.
A finger-protecting creasing device 16 is shown as being held between the thumb and forefinger of the right hand to pinch the sheet 10 at point S and apply pressure to the crease line 18. The device 16 is then drawn in the direction of arrow 20 in very much the same fashion as can be customarily done between one's finger and thumb tips. The paper can be creased with controllable thumb pressure applied directly over line 18 for a sharp or somewhat sharp crease, or the crease can be made closer to the throat of the device (with the thumb and finger tips inwardly of the line 18) with reduced pressure being applied, if a more gentle crease (less sharp) is desired.
The device 16 of the preferred form of my invention is shown in FIGS. 2-6. It consists of a pair of slightly flexible arms 22 and 24, a hinge portion 26 and at least one side wing or flange 28. Ideally, parts 22, 24, 26 and 28 are integral and made of plastic for purposes of long life, but it can also be made of several components and of other materials. The hinge, when the device is made of plastic, may be a conventional "living hinge" with a throat portion 29. Considered within the scope of the term hinge is anything which allows the device 16 to be open (V-shaped) at the end opposite the hinge for placement over a line to be creased when the device is inactive, and then permit arm 22 to be relatively movable toward arm 24 to an active creasing condition to the dotted line positions shown in FIGS. 2 and 10. In such creasing condition, arms 22 and 24 are essentially parallel, at least at the section where finger pressure is applied. A flexible arm such as illustrated in FIG. 10 may be considered hinged for purposes of this invention, for example. The arms 22 and 24 have opposing facing creasing surfaces X and Y, which, when the arms are brought together as in FIGS. 2 and 10, establish a fairly large area of surface contact between the creasing surfaces and the sheet being creased.
The preferred form of article shown in FIGS. 2-6 also incorporates an envelope-opening feature and a paper combing feature. Envelope opening is performed by slitting with a stiletto-type guide 23 having a pointed tip 25 and an opening 27 extending lengthwise between the guide 23 and the adjacent edge of flange 28. The guide 23 may have a sharpened edge 31, and may even be provided with an embedded razor edge 33 (FIG. 4), or can have both. As the function of such an envelope opener is well known, it need not be further described here, except to say that the envelope would be slit by entering tip 25 into an open corner below a flap 21 as shown in FIG. 4, with the guide 23 then being moved in the direction of arrow 19. A bulbous portion 17 may be provided on one or both sides of the end of the guide 23 opposite from tip 25 to spread the envelope during slitting.
In addition, a resilient friction-creating comb or snubber 35 is provided at the cantilevered end on the outer surface of the arm 22, and is used to comb sheets by either pushing them in from a pile edge as shown in FIG. 5 or pulling them in as shown in FIG. 6.
For ease of picking up device 16 as well as using it for display purposes to be described later, arms 22 and 24 are desired to be of the same length. This enables the device to be stood upright on a surface 32, e.g., the top of a desk (FIG. 2). When so standing and with the flange 28 being located away from the user, it becomes simple for the person to place the forefinger and middle finger over the flange 28, capture it between those fingers and lift it into ready position for placement over a sheet fold and creasing it. Finger placement is depicted in FIG. 3, where the two dotted-line circles on opposite sides of the flange 28 are representative of the forefinger and middle finger. The thumb is also shown in dotted lines, ready to apply pressure to the arm 22 and sheet 10 at the crease line 18. This is accomplished by relatively pressing arm 22 and arm 24 toward each other in a pinching-type motion. The reason I have illustrated a thumb against arm 22 in FIGS. 1-3 is that greater pressure can normally be applied by a thumb as compared to a finger, such as when folding and creasing multiple sheets. The thumb also seems better able to control the amount of pressure applied, depending on how little or how much pressure is desired to form a specific sharpness of crease. FIG. 3 shows a flange 28' in dotted lines. Both flanges 28 and 28' may be used on the device to make it usable by either a right or left handed person. When two flanges are used, the flanges tend to grip the sides of the forefinger lightly and keep the device from falling from the user's hands if other tasks are also being undertaken while creasing is intended to continue.
FIG. 7 illustrates a slight modification from the preferred form of device. In this version, the flange 28B is located centrally of arm 24B. This makes a single flange readily usable by either a right or left handed person. It will be noted from several of the views that the outer tips or ends of the arms 22 and 24 are perpendicular to the length of the arms, making them squared or blunt. This is what enables the device to stand upright and vertically on surface 32, in inverted V fashion. Flange 28B is easily gripped between the forefinger and middle finger in the same manner as the flange of device 16.
FIG. 8 illustrates one simple manner in which a version of the device 16C dedicated solely to creasing can be produced, with or without the addition of the flange 28C'. It can be made from flat stock and thinned out at 34 and 36 to form a right angled portion and the hinge. A logo or advertising message may be printed or otherwise formed in what will become the outer surfaces of arms 22C and 24C when the device is made to stand on the surface 32. The logo may also be on the outer side of either or both flanges 28C, 28C'. The creases 34 and 36 may be designed so that flange 28C and arms 22C and 24C adopt their positions of FIGS. 2 and 3, while still allowing the hinge 26C to perform its function.
Flanges 28, 28B and 28C also constitute a slippage-resisting gripping means to maintain the device firmly under control as it is drawn along the crease. In effect, the flanges are a positive means to prevent the fingers from sipping off the device. However, it is also contemplated that frictional means on the outside surfaces of arms 22 and 24 may also perform to some extent, although not as well.
FIGS. 9 and 10 show another modified form of creasing device 16D. FIG. 9 is a view taken from above, looking in the same direction as in FIGS. 3 and 7, while FIG. 10 is a cross-section of FIG. 9 taken along lines 10--10. This version has a ring portion 40 which may be open as at 42 to accommodate fingers of different diameters. Clearly, this variation is best molded from thermoplastic, one having sufficient resilience to enable expansion and contraction to be received by large or small fingers. FIG. 10 illustrates multiple sheets being creased, e.g., a multi-part computer form. Arm 22D is shown somewhat flexed adjacent the hinge end, this showing being exaggerated to illustrate what can occur when a simple bend forms the hinge and the arm 22D is capable of slight flexing.
Whether the device is dedicated solely to creasing or also includes the envelope opening or sheet combing features, it is always held the same way. This is illustrated by the dotted-line fingers in FIG. 2 and 4. It should be understood that the same manner of finger gripping is also used when sheet combing as in FIGS. 5 and 6.
Depending on the particular form of device, one or more exposed surfaces can carry a logo or advertising message (FIG. 8). Since the device can be made to stand upright on the blunt ends of the arms for grasping by the user, the logo should be made to be readable when the device is upright. This advantageously exposes the user to frequent sight of the logo. This makes the device an exceptional promotional item for products and services associated with business use.
It can be seen that my invention lends itself to many differently-designed forms, and the illustrated forms are not intended to limit the claims only to those variations shown. Various other modifications can be made without departing from the spirit and scope of the method and article claimed. | A method and device are provided to protect one's fingers from abrasion and paper cuts whenever forming a creasing line. The device consists of a pair of laterally-positioned elongated arms which are capable of providing a controllable creasing pressure at inwardly-facing opposed creasing surfaces. One of the arms is provided with a finger-gripping means to enable achieving a firm hold on the device during use as well as to prevent slippage of one's fingers from the device as it is moved while the crease is being formed. A stiletto-type letter opener and a sheet comber can also be provided with the device. The device can be made to stand upright on a desk for ready grasping in the identical position in which it will be used, and also has surfaces which are capable of carrying an advertising message or logo which are easily readable when the device is placed in such upright position. | 1 |
This application claims the benefit of U.S. Provisional Patent Application No. 61/933,947, filed Jan. 31, 2014, the entirety of which is incorporated herein by reference.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to transgenic fish, particularly red transgenic fish.
2. Description of Related Art
Transgenic technology involves the transfer of a foreign gene into a host organism enabling the host to acquire a new and inheritable trait. Transgenic technology has many potential applications. For example, it can be used to introduce a transgene into a fish in order to create new varieties of fish. There are many ways of introducing a foreign gene into fish, including: microinjection (e.g., Zhu et al., 1985; Du et al., 1992), electroporation (Powers et al., 1992), sperm-mediated gene transfer (Khoo et al., 1992; Sin et al., 1993), gene bombardment or gene gun (Zelenin et al., 1991), liposome-mediated gene transfer (Szelei et al., 1994), and the direct injection of DNA into muscle tissue (Xu et al., 1999). The first transgenic fish report was published by Zhu et al., (1985) using a chimeric gene construct consisting of a mouse metallothionein gene promoter and a human growth hormone gene. Most of the early transgenic fish studies have concentrated on growth hormone gene transfer with an aim of generating fast growing fish. While a majority of early attempts used heterologous growth hormone genes and promoters and failed to produce these fish (e.g. Chourrout et al., 1986; Penman et al., 1990; Brem et al., 1988; Gross et al., 1992), enhanced growth of transgenic fish has been demonstrated in several fish species including Atlantic salmon, several species of Pacific salmons, and loach (e.g. Du et al., 1992; Delvin et al., 1994, 1995; Tsai et al., 1995).
The black skirt tetra ( Gymnocorymbus ternetzi ) has been commercially cultured in the United States at least as early as 1950 (Innes, 1950). However, for the ornamental fish industry the dark striped pigmentation of the adult black skirt tetra does not aid in the efficient display of the various colors. The albino black skirt tetra, or “white tetra” is a variant that arose during domestication and shows decreased pigmentation. The availability of such fish having modified pigmentation for transgenesis with fluorescent proteins would result in better products for the ornamental fish industry due to better visualization of the various colors.
Many fluorescent proteins are known in the art and have been used to investigate various cellular processes, including fluorescent proteins exhibiting various green, red, pink, yellow, orange, blue, or purple colors. Although transgenic experiments involving fluorescent proteins have provided new markers and reporters for transgenesis, progress in the field of developing and producing ornamental fish that express such proteins has been limited.
SUMMARY OF THE INVENTION
In certain embodiments, the present invention concerns making transgenic fluorescent fish and providing such fish to the ornamental fish industry.
In some embodiments, transgenic fish or methods of making transgenic fish are provided. In certain aspects, the transgenic fish are fertile, transgenic, fluorescent fish. In a particular embodiment, the fish for use with the disclosed constructs and methods is the white tetra. Tetra skin color is determined by pigment cells in their skin, which contain pigment granules called melanosomes (black or brown color), xanthosomes (yellow color), erythrosomes (orange or red color), or iridosomes (iridescent colors, including white color). The number, size, and density of the pigment granules per pigment cell influence the color of the fish skin. White tetra have diminished number, size, and density of melanosomes and hence have lighter skin when compared to the wild type black skirt tetra.
In certain specific embodiments there are provided transgenic tetra or progeny thereof comprising specific transgenic integration events, referred to herein as transformation events. These fish are of particular interest because, for example, they embody an aesthetically pleasing red color. Transgenic fish comprising these specific transgenic events may be homozygous or heterozygous (including, for example, hemizygous) for the transformation event. Homozygous fish bred with fish lacking a transformation event will in nearly all cases produce 100% heterozygous offspring. Eggs, sperm, and embryos comprising these specific transgenic events are also included as part of the invention.
In one such embodiment regarding a specific transgenic integration event, a red transgenic tetra or progeny thereof is provided comprising chromosomally integrated transgenes, wherein the tetra comprises the “Red tetra 1 transformation event,” sperm comprising the Red tetra 1 transformation event having been deposited as ECACC accession no. 14011701. The chromosomally integrated transgenes may be present on one integrated expression cassette or two or more integrated expression cassettes. In certain aspects, such a transgenic tetra is a fertile, transgenic tetra. In more specific aspects, such a tetra is a transgenic White tetra. Such a transgenic tetra may be homozygous or heterozygous (including, for example, hemizygous) for the transgenes or integrated expression cassette(s).
Also disclosed are methods of providing a transgenic tetra comprising the Red tetra 1 transformation event to the ornamental fish market. In some embodiments, the method comprises obtaining a transgenic tetra or progeny thereof comprising chromosomally integrated transgenes, wherein the tetra comprises the “Red tetra 1 transformation event,” sperm comprising the Red tetra 1 transformation event having been deposited as ECACC accession no. 14011701, and distributing the fish to the ornamental fish market. Such fish may be distributed by a grower to a commercial distributor, or such fish may be distributed by a grower or a commercial distributor to a retailer such as, for example, a multi-product retailer having an ornamental fish department.
In some aspects, methods of producing a transgenic tetra are provided comprising: (a) obtaining a tetra that exhibits fluorescence and comprises one or more chromosomally integrated transgenes or expression cassettes, wherein the tetra comprises the “Red tetra 1 transformation event,” sperm comprising the Red tetra 1 transformation event having been deposited as ECACC accession no. 14011701; and (b) breeding the obtained tetra with a second tetra to provide a transgenic tetra comprising the Red tetra 1 transformation event. The second tetra may be a transgenic or non-transgenic tetra.
In further embodiments, also provided are methods of producing a transgenic organism, the method comprising using sperm comprising the Red tetra 1 transformation, such sperm having been deposited as ECACC accession no. 14011701, to produce transgenic offspring. Such offspring may be, for example, a tetra, a species of the Gymnocorymbus genus, a fish species or genus related to tetra, or another fish species or genus. In some aspects, the fish may be produced using in vitro fertilization techniques known in the art or described herein.
As used in this specification, “a” or “an” may mean one or more. As used herein in the claim(s), when used in conjunction with the word “comprising,” the words “a” or “an” may mean one or more than one.
The use of the term “or” in the claims is used to mean “and/or” unless explicitly indicated to refer to alternatives only or the alternatives are mutually exclusive, although the disclosure supports a definition that refers to only alternatives and “and/or.” As used herein “another” may mean at least a second or more.
Throughout this application, the term “about” is used to indicate that a value includes the inherent variation of error for the device, the method being employed to determine the value, or the variation that exists among the study subjects.
Any embodiment of any of the present methods, kits, and compositions may consist of or consist essentially of—rather than comprise/include/contain/have—the described features and/or steps. Thus, in any of the claims, the term “consisting of” or “consisting essentially of” may be substituted for any of the open-ended linking verbs recited above, in order to change the scope of a given claim from what it would otherwise be using the open-ended linking verb.
Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.
DETAILED DESCRIPTION OF THE INVENTION
Transgenic Fish
In some aspects, the invention regards transgenic fish. Methods of making transgenic fish are described in, for example, U.S. Pat. Nos. 7,135,613; 7,700,825; 7,834,239, each of which is incorporated by reference in its entirety.
It is preferred that fish belonging to species and varieties of fish of commercial value, particularly commercial value within the ornamental fish industry, be used. Such fish include but are not limited to catfish, zebrafish and other danios, medaka, carp, tilapia, goldfish, tetras, barbs, sharks (family Cyprinidae), angelfish, loach, koi, glassfish, catfish, discus, eel, tetra, goby, gourami, guppy, Xiphophorus, hatchet fish, Molly fish, or pangasius. A particular fish for use in the context of the invention is a tetra, Gymnocorymbus ternetzi . Tetra are increasingly popular ornamental animals and would be of added commercial value in various colors. Tetra embryos are easily accessible and nearly transparent. A fish that is of particular use with the disclosed constructs and methods is the White Tetra. Tetra skin color is determined by pigment cells in the skin, which contain pigment granules called melanosomes. The number, size, and density of the melanosomes per pigment cell influence the color of the fish skin. White Tetra have diminished number, size, and density of melanosomes and hence have lighter skin when compared to the wild type tetra.
Fertilization from Frozen Sperm
Fish sperm freezing methods are well-known in the art; see, e.g., Walker and Streisinger (1983) and Draper and Moens (2007), both of which are incorporated herein by reference in their entireties. To obtain the transgenic fish disclosed herein, frozen tetra sperm may be used to fertilize eggs.
Briefly, one or two breeding pairs of tetra should be placed in a shoebox with an artificial spawning mat. The water level in the shoebox should be ˜2-3 inches and kept at 75-85° F. Low salinity (conductivity 100-200 uS/cm) and slight acidity (˜pH 6.9) promote spawning. The fish may be exposed to a natural or artificial light cycle; the photoperiod starts at 8 am and ends at 10 pm. The following morning, remove and discard the eggs. Tetra may be anesthetized by immersion in tricaine solution at 16 mg/100 mL water. After gill movement has slowed, remove one female, rinse it in water, and gently blot the belly damp-dry with a paper towel. The eggs should not be exposed to water as this will prevent fertilization. Gently squeeze out the eggs onto a slightly concave surface by applying light pressure to the sides of the abdomen with a thumb and index finger and sliding the fingers to the genital pore. Ready to spawn females will release the eggs extremely easily, and care should be taken not to squeeze the eggs out while blotting the fish. Good eggs are yellowish and translucent; eggs that have remained in the female too long appear white and opaque. The females will release the eggs only for an hour or so. Eggs from several females may be pooled; the eggs can be kept unfertilized for several minutes. The sperm is thawed at 33° C. in a water bath for 18-20 seconds. 70 μl room temperature Hanks solution is added to the vial and mixed. The sperm is then immediately added to the eggs and gently mixed. The sperm and eggs are activated by adding 750 μl of fish water and mixing. The mixture is incubated for 5 minutes at room temperature. The dish is then filled with fish water and incubated at 28° C. After 2-3 hours, fertile embryos are transferred to small dishes where they are further cultured.
Parichy and Johnson, 2001, which is incorporated by reference in its entirety, provides additional examples regarding in vitro fertilization.
The invention further encompasses progeny of a transgenic fish containing the Red tetra 1 transformation event, as well as such transgenic fish derived from a transgenic fish egg, sperm cell, embryo, or other cell containing a genomically integrated transgenic construct. “Progeny,” as the term is used herein, can result from breeding two transgenic fish of the invention, or from breeding a first transgenic fish of the invention to a second fish that is not a transgenic fish of the invention. In the latter case, the second fish can, for example, be a wild-type fish, a specialized strain of fish, a mutant fish, or another transgenic fish. The hybrid progeny of these matings have the benefits of the transgene for fluorescence combined with the benefits derived from these other lineages.
The simplest way to identify fish containing the Red tetra 1 transformation event is by visual inspection, as the fish in question would be red colored and immediately distinguishable from non-transgenic fish.
EXAMPLES
Certain embodiments of the invention are further described with reference to the following examples. These examples are intended to be merely illustrative of the invention and are not intended to limit or restrict the scope of the present invention in any way and should not be construed as providing conditions, parameters, reagents, or starting materials that must be utilized exclusively in order to practice the art of the present invention.
Example 1
Red Transgenic Tetra
Transgenic fish exhibiting a red color are provided. The specific transgenic events embodied in these fish are designated the “Red tetra 1 transformation event”. Sperm from these fish may be used to fertilize tetra eggs and thereby breed transgenic tetra that comprise these specific transgenic integration events. Sperm from this line was deposited at the European Collection of Cell Cultures (ECACC), Public Health England, CRYOSTORES, Bld. 17, Porton Down, Salisbury, SP4 OJG, United Kingdom, under the provisions of the Budapest Treaty as “Red tetra 1” (the deposit was designated as accession no. 14011701).
The fluorescent transgenic fish have use as ornamental fish in the market. Stably expressing transgenic lines can be developed by breeding a transgenic individual with a wild-type fish, mutant fish, or another transgenic fish. The desired transgenic fish can be distinguished from non-transgenic fish by observing the fish in white light, sunlight, ultraviolet light, blue light, or any other useful lighting condition that allows visualization of the red color of the transgenic fish.
The fluorescent transgenic fish should also be valuable in the market for scientific research tools because they can be used for embryonic studies such as tracing cell lineage and cell migration. Additionally, these fish can be used to mark cells in genetic mosaic experiments and in fish cancer models.
All of the compositions and/or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and/or methods and in the steps or in the sequence of steps of the methods described herein without departing from the concept, spirit and scope of the invention. More specifically, it will be apparent that certain agents that are both chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope, and concept of the invention as defined by the appended claims.
REFERENCES
The following references, to the extent that they provide exemplary procedural or other details supplementary to those set forth herein, are specifically incorporated herein by reference.
U.S. Pat. No. 7,135,613 U.S. Pat. No. 7,700,825 U.S. Pat. No. 7,834,239 Brem et al., Aquaculture, 68:209-219, 1988. Chourrout et al., Aquaculture, 51:143-150, 1986. Delvin et al., Nature, 371:209-210, 1994. Draper and Moens, In: The Zebrafish Book, 5 th Ed.; Eugene, University of Oregon Press, 2007. Du et al., Bio/Technology, 10:176-181, 1992. Innes, W. T., Exotic Aquarium Fishes : A work of general reference, Innes Publishing Company, Philadelphia, 1950. Gross et al., Aquaculature, 103:253-273, 1992. Khoo et al., Aquaculture, 107:1-19, 1992. Lamason et al., Science, 310(5755):1782-1786, 2005. Penman et al., Aquaculture, 85:35-50, 1990. Powers et al., Mol. Marine Biol. Biotechnol., 1:301-308, 1992. Sin et al., Aquaculture, 117:57-69, 1993. Szelei et al., Transgenic Res., 3:116-119, 1994. Tsai et al., Can. J. Fish Aquat. Sci., 52:776-787, 1995. Walker and Streisinger, Genetics 103: 125-136, 1983. Xu et al., DNA Cell Biol., 18, 85-95, 1999. Zelenin et al., FEBS Lett., 287(1-2):118-120, 1991. Zhu et al., Z. Angew. Ichthyol., 1:31-34, 1985. | The present invention relates to transgenic red ornamental fish, as well as methods of making such fish by in vitro fertilization techniques. Also disclosed are methods of establishing a population of such transgenic fish and methods of providing them to the ornamental fish industry for the purpose of marketing. | 0 |
This application is a division of my pending U.S. application Ser. No. 522,093, filed Aug. 11, 1983 for Vibratory Grain Separating Apparatus, Etc.
DETAILED DESCRIPTION OF THE INVENTION
This invention relates to a vibratory grain separating apparatus used with a rice-hulling apparatus for separating these hulled and unhulled rice from a mixture thereof.
An object of the present invention is to permit separation of the unhulled and hulled rice directly from the process grain emerging from the rice-hulling apparatus without leaving the half-hulled rice.
Another object of the present invention is to provide a rice-hulling apparatus, in which the vibratory grain separating apparatus noted is integrally assembled.
A further object of the present invention is to minimize the size of the vibratory grain separating apparatus.
Harvested unhulled rice is hulled by a rice-hulling apparatus to obtain hulled rice, which is then cleaned by a cleaning apparatus. When the hulling is done by adjusting the rice-hulling apparatus such that 100% hulled rice can be obtained through a single cycle, broken rice is liable to result due to an excessive hulling action. Usually, therefore, the hulling pressure is adjusted 70 to 80% of the supplied unhulled rice, the remaining 20 to 30% of rice being left unhulled.
The rice-hulling apparatus, accordingly, is always provided with a separating apparatus for separating the unhulled and hulled rice.
The prior art separating apparatus separates the supplied mixture grain into unhulled rice, hulled rice and half-hulled rice. The unhulled rice is returned to the rice-hullng apparatus for hulling afresh. The hulled rice is taken out as finished rice, which is usually cleaned subsequently. The half-hulled rice is returned to a supply section of the separating apparatus and re-circulated for separating afresh.
To facilitate the understanding of the present invention, the construction of the prior art separating apparatus having the functions noted above will now be described. Referring to FIGS. 1 and 2, which illustrate the prior art pertaining to the present invention, designated at A is a separating element. Its top surface has a number of protuberances B. The grain C to be separated is put on this separating surface of the element A, and the element A is reciprocated in oblique directions shown by arrows W. The protuberances B offers frictional resistance against the flow of the grain C, so that the grain C is progressively directed in the direction of arrow D.
This well-known separating element A is mounted on a base member E as shown in FIG. 2. More particularly, the separating element A is linked to the top of the base member E by inclined rod links F. The separating element A is also coupled to an excentric cam G by a rod H. When the excentric cam G is rotated, the separating element A is reciprocated in the directions of arrows W via the rod H. The separating element A is a rectangular shape. The grain C is supplied from the side I of one of its opposite elongate transversal edges and is discharged from the side J of the other edge. It has a lower and higher end K and L in the transversal direction normal to the line connecting the supply and discharge sides I and J, and it is inclined by an angle α.
Designated at M is a supply hopper. The grain C is supplied from a gap on the supply side I adjacent to the upper side L. The discharge side J is open over the entire width. An unhulled rice outlet N and a hulled rice outlet P are provided on the discharge side J adjacent to the lower and upper sides K and L, respectively. A half-hulled rice outlet Q is provided between the outlets N and P.
Mixture rice consisting of unhulled and hulled rice is supplied from said supply hopper M to this separating element while the excentric cam G is rotated to reciprocate the separating element A in the directions of arrows W, whereby the mixture rice on the separating element A is vibrated. Thus, there takes place a primary separating phenomenon that the mixture rice is separated in vertical directions on the separating surface, with the heavier hulled rice sinking while the unhulled rice rising. The hulled rice gathering in the lower layer touches the element A and experiences an upward thrust. This gives rise to a secondary phenomenon that the hulled rice is deflected to proceed toward the upper end L along an orbit as shown at T1 in FIG. 2 so that it is taken out through a hulled rice outlet P. The unhulled rice which is lighter in weight than the hulled rice floats up and flows over the hulled rice layer toward the lower end. That is, it is deflected to proceed along anorbit T2 toward the lower end K so that it is taken out through an unhulled rice outlet N. Intermediate between the upper and lower ends, half-hulled rice is concentrated as shown at T3 to be taken out through a half-hulled rice outlet Q.
The half-hulled rice must be returned to the separating element A for separating it again. The prior art separating apparatus, therefore, requires a half-hulled rice returning means. If there is a separating apparatus which will never discharge any half-hulled rice, no half-hulled rice returning means is necessary, and the price of the apparatus can be reduced that much.
The present invention is intended in the light of the above, and it will now be described with reference to the accompanying drawings, in which:
FIG. 1 is a fragmentary enlarged-scale sectional view showing a prior art separating apparatus;
FIG. 2 is an elevational view of the prior art separating apparatus;
FIG. 3 is a front view showing a separating apparatus according to the present invention;
FIG. 4 is a side view of the same;
FIG. 5 is a view similar to FIG. 3 but with the transversal inclination angle of a separating element adjusted to a different angle;
FIG. 6 is a perspective view showing an excentric cam and a rod;
FIG. 7 is a plan view showing the separating element;
FIG. 8 is a plan view showing the separating element in operation;
FIG. 9 is a longitudinal cross-sectional view of the separating element;
FIGS. 10 through 12 are sectional views illustrating the separating operation of the separating element;
FIG. 13 is a schematic view showing a rice-hulling apparatus incorporating the separating element according to the present invention;
FIG. 14 is a perspective view of the same;
FIG. 15 is a side view of the same;
FIG. 16 is a plan view of the same;
FIG. 17 is a perspective view showing part of the same; and
FIG. 18 is a longitudinal cross-sectional view of the same.
The vibratory grain separating apparatus according to the present invention will now be described with reference to FIG. 3 and following Figures. Reference numeral 21 designates a separating element. As shown in FIG. 7, its shape is rectangular and elongate in the transversal direction, that is, its dimension 22 normal to the transversal direction is smaller than its transversal dimension 23. It has front and rear upright edge walls 24 and 25 extending over its entire transversal length. Its front portion covering two-third of its surface area has hulled rice moving protuberances 26 inclined toward the left, these protuberances being arranged over the entire front portion. Its rear portion covering one-third of the surface area has unhulled rice moving protuberances 27 inclined to the right, these protuberances being arranged over the entire rear portion. As is clearly seen from the side sectional view of FIG. 9, the protuberances 26 and 27 are inclined upwards toward the front upright edge wall 24.
The separating element 21 has a hulled rice outlet 28 formed on the left side of the front portion, while the rest of the left side is closed by a left side wall 29. It also has an unhulled rice outlet 30 formed on the right side of the rear portion, while the rest of the right side is closed by a right side wall 31.
A supply hopper 32 is found over the front portion of the separating element 21 adjacent to the unhulled rice outlet 30. A base member 45 is coupled by front and rear arms 34a and 34b to a lower frame 33. Each front arm 34a is pivoted at the lower end by a pin 47 to the front wall of the lower frame 33. A rotary shaft 37 adjustable in the transversal direction is rotatably mounted in a rear portion of the lower frame 33. As shown in FIG. 3, the rotary shaft 37 has oppositely cut threads 42a and 42b formed on the opposite sides of its axial center. Female thread members 38a and 38b are fitted on the respective threads 42a and 42b. The lower end of the rear arms 34b is mounted on a vertically movable shaft 40 extending beneath and parallel to the rotary shaft 37. Bosses 41a and 41b are mounted on the vertically movable shaft 40. The female thread member 38a and boss 41a are coupled together by a rod 39a, while the other female thread member 38b and boss 41b are coupled together by a rod 39b. A left side portion of the separating element 21 is linked by a pin 43 to the top of the corresponding portion of the base member 45. The right end of the base member 45 has a female thread member 44, in which a vertical adjusting screw 46 is screwed. The upper end of the adjusting screw 46 is coupled to the bottom of the separating element 21.
Reference numeral 35 designates an excentric cam having a rod 36, which is pivoted at the upper end to the base member 45 near the upper end of arm 34a. The angle θ between the arm 34a and rod 36 is smaller than the right angles so that the base member 45 can return quickly. FIG. 6 shows a perspective view of the rod 36. It has an upwardly flaring portion.
FIG. 13 and following Figures illustrate a rice-hulling apparatus which incorporates the separating apparatus described above. It comprises a lifter 51 including an upper and lower guide roller 52 and 53, round which an endless belt 54 with buckets is passed. The lifter 51 has a side inlet 55 provided at the lower end, and a side hopper 56 is mounted at the side inlet 55. The lifter 51 also has an outlet 57 provided at the top. A stationary hopper 58 is mounted on the outlet 57. The stationary hopper 58 is made of a plastic material. It is possible to fabricate the frame of the lifter 51 and the stationary hopper 58 as a one-piece plastic molding. The stationary hopper 58 is stationary and not vertically moved. It is secured by bolts to the outlet 57. The lower end of the stationary hopper 58 is secured to the top of a frame 60 of the hulling section 59.
The plastic stationary hopper 58 in this arrangement serves to temporarily store grain and also firmly hold the top of the lifter 51. Especially, the latter effect is considerably great. In the prior art rice-hulling apparatus the top of the lifter is very unstable and is vibrated with the vibratory separating apparatus because the vertically movable storage tank is suspended from it. The stationary hopper 58 has an over-flow hole 61 formed at an intermediate position. An on-off valve 62 is provided at the outlet of the stationary hopper 58. The hulling section 59 accommodates a pair of hulling rollers 63 and 64 disposed such that their shafts 65 and 66 lie in an oblique plane. The shafts 65 and 66 extend parallel to the guide rollers 52 and 53. A delivery roller 67 is provided immediately beneath the on-off valve 62. A guide plate 68 is provided beneath the delivery roller 67, such that the grain departing therefrom is directed to between the hulling rollers 63 and 64.
A blower 69 is provided on the frame 60 beneath the guide plate 68. It is transversally elongate and extends substantially over the full width of the apparatus. Air is forced out from the blower 69 through an air passage 70 to be led past the underside of the hulling rollers 63 and 64 into an air-blow separating section 71. A vibratory dispersing member 72 is provided on the discharge side of the hulling rollers 63 and 64 and serves to disperse the process material emerging from between the hulling rollers 63 and 64 in the direction of the width of the apparatus.
A withdrawal blower 73 is mounted on one side wall of the frame of the air-blow separating section 71. Its shaft 74 has an excentric cam 75 having an integral rod 76 which is secured at the other end to the vibratory dispersing member 72.
The lower end of the vibratory dispersing member 72 is biasedly supported by a leaf spring 77, and its outlet 78 is flaring downwards. With the rotation of the excentric cam 75, the outlet 78 is quickly reciprocated in oblique directions, thereby causing the process grain supplied from the hulling section 59 to be dispersed in the transversal directions.
A distributing gutter 79 is disposed beneath the outlet 78. The upper surface of its bottom has a number of protuberances 80. It is secured to the top of a multi-element separator consisting of a plurality of separating elements 21 as described above stacked one above another. Reference numeral 87 designates an unhulled rice return inlet, 88 (FIG. 16) a hulled rice gutter, 89 a hulled rice lifter, 90 a hulled rice storage tank, 91 a vibratory separating section, and 92 a filter.
In operation, the unhulled rice a (FIG. 13) supplied to the lifter 51 is lifted to be supplied to the hulling section 59. The hulling section 59 produces a combination (FIGS. 8-12) of unhulled rice a, hulled rice b and hull c. This processed grain is supplied to the air-blow separating section 71 where the hull c is separated by air blown against it. The remaining unhulled and hulled rice a and b is led into the vibratory separating section 91. The separated unhulled rice a is returned to the lifter 51, while the separated hulled rice b is led to the outside of the apparatus.
More specifically, the material unhulled rice a supplied to the side inlet 55 is by belt 54 with buckets through the lifter 51 and discharged through the outlet 57 into the stationary hopper 58 to be stored therein. When the amount of grain stored exceeds a predetermined quantity, it over-flows through the over-flow hole 61 to be returned to the side inlet 55. By opening the on-off valve 62, the grain stored in the stationary hopper 58 is delivered by the delivery roller 67 onto the inclined guide plate 68. The grain falling onto the guide plate 68 flows therelong to be directed therefrom to between the hulling rollers 63 and 64 arranged in an oblique relation to each other. The process grain emerging from between the hulling rollers 63 and 64 enters the vibratory dispersing member 72. Since the shaft 74 of the withdrawal blower 73 is being rotated in unison with the eccentric cam 75 mounted on it, the rod 76 with the upper end thereof secured to the eccentric cam 75 is reciprocated in oblique directions, whereby the vibratory dispersing member 72 secured to the lower end of the rod 76 is reciprocated in oblique directions. While the vibratory dispersing member 72 is reciprocated, it is elastically supported by the leaf spring 77.
The process grain in the vibratory dispersing member 72 thus falls therefrom in a state uniformly dispersed in the width direction into the distributing gutter 79. The blower 69 withdraws air and forces it through the air passage 70. The air issuing from the air passage 70 proceeds past the underside of the vibratory dispersing member 72 and then through the process matter falling from the outlet 78 into an upper space in the air-blow separating section 71. As the air proceeds through the falling process grain, it blows out the hull c which is light in weight. The blown-out hull c is withdrawn by the withdrawal blower 73 to be discharged to the outside of the apparatus.
The resultant mixture rice, now free from the hull c, falls onto the distributing gutter 79 to be distributed therethrough to the individual separating elements 21. Each separating element 21 operates as follows. Since the angle θ between the arm 34a and rod 36 is smaller than the right angles, the separating element 21 is moved quickly in the return stroke, i.e., from the front side to the rear side, and rather slowly in the converse direction with the rotation of the excentric cam 35, the ratio of the return speed to the forward speed being 1:1.01-1.2.
The mixture rice consisting of the unhulled and hulled rice a and b supplied to the separating element 21 is initially in a state of entirely half-hulled rice as shown in FIG. 10. As it experiences a back-and-forth vibratory motion in horizontal or oblique directions, the primary phenomenon noted previously takes place, with the heavier hulled rice b sinking and the lighter unhulled rice a floating up to form an upper layer. The sinking hulled rice b touches the hulled rice moving protuberances 26 and unhulled rice moving protuberances 27.
The contact of the hulled rice b with the protuberances 26 and 27 gives rise to the secondary phenomenon noted previously. That is, the hulled rice b gradually proceeds toward the front upright edge wall 24 of the separating element 21, so that it forms a comparatively thick layer on the front portion of the separating element 21. On the other hand, its layer formed on the rear portion of the separating element 21 is comparatively thin. With the formation of a difference in the thickness between the front and rear portions of the hulled rice layer on the separating element 21, the unhulled rice a floating up to the surface of the front portion of the hulled rice layer is caused to move thereover toward the rear portion of the separating element 21.
The extent of this secondary phenomenon is adjusted by turning the adjusting shaft 37. By turning the adjusting shaft 37, the female thread members 38a and 38b screwed on the oppositely cut threads 42a and 42b are brought toward or away from each other to cause the rods 39a and 39b be more inclined or more upright. This motion of the rods 39a and 39b causes a vertical displacement of the vertically movable shaft 40, whereby the back-and-forth inclination of the separating element 21 is adjusted via the rear arms 34b.
As the sequence of phenomena described above proceeds, there occurs a tertiary phenomenon that the hulled rice b gathering as a thick layer on the front portion of the separating element 21 turns to be moved to the left along the front upright edge wall 24 by the action of the top of the hulled rice moving protuberances 26. During this leftward movement of hulled rice, the protuberances 26 and 27 continually provide the separating action on the hulled rice b in contact with them. Thus, as the hulled rice layer moves along the front upright edge wall 24, its thickness is progressively increased. Eventually, an upper portion of the hulled rice layer turns to flow toward the rear portion of the separating element 21. This has an effect of increasing the purity of the hulled rice b, so that when the hulled rice layer reaches the hulled rice outlet 28, it completely consists of the hulled rice b. The movement of the hulled rice b toward the hulled rice outlet 28 is chiefly caused by the tip of the hulled rice moving protuberances 26. The hulled rice moving protuberances 26 has a far greater area than that of the unhulled rice moving protuberances 27, so that they can reliably cause movement of the hulled rice b.
The unhulled rice a, meanwhile, slides over the inclined surface of the hulled rice layer toward the rear portion of the separating element 21. On the rear portion of the separating element 21, there takes place a quaternary phenomenon that the unhulled rice a is moved to the right by the action of the unhulled rice moving protuberances 27. While the unhulled rice a is moved to the right over the separating element 21 by the action of the unhulled rice moving protuberances 27, the secondary phenomenon of separating is still in force. The purity of the unhulled rice a thus is progressively increased, so that perfectly unhulled rice is taken out through the unhulled rice outlet 30.
The extents of the tertiary phenomenon, i.e., the movement of the hulled rice a toward the hulled rice outlet 28, and the quaternary phenomenon, i.e., the movement of the unhulled rice b toward the unhulled rice outlet 30, are adjusted by adjusting the transversal inclination of the separating element 21. That is, by turning the adjustment screw 46 the transversal inclination of the separating element 21 is adjusted, and the extents of the tertiary and quaternary phenomena are subtly adjusted according to the extent of the inclination.
During the separating operation described above, half-hulled rice remain revolving on a central portion of the separating element 21. That is, it is never let to the outside of the separating element 21, but only the hulled and unhulled rice b and a are renewed.
The separated unhulled rice a is led through the hulled rice outlet 30 to the filter 92 where large foreign particles are separated, and only the unhulled rice a having passed through the filter is returned to the unhulled rice return inlet 87 and re-circulated together with the newly supplied unhulled rice by the belt 54 with buckets for hulling afresh.
The hulled rice taken out through the hulled rice outlet 28 flows along the hulled rice gutter 88 into the hulled rice gutter 89 where it is lifted to be stored in the hulled rice storage tank 90 and measured and packed in a measuring and packing device provided beneath the tank 90. The packed product rice is transported to a given position. | A vertically disposed unhulled rice lifter is mounted adjacent a stationary frame with its upper end secured against movement relative to and in communication with a hulling section which is secured on the frame above and to one side of a vibratory separating section of the apparatus. Grain from the lifter is hulled between a pair of hulling rolls in the hulling section and is fed downwardly through an air stream on to a vibrating surface on the vibratory separating section. The air stream conveys away hulls and dust from the hulled rice; and the vibrating surface separates the hulled rice grains from any unhulled rice which may have passed through the hulling section. The unhulled portion of grain is then returned to the lifter and the completely hulled grains are conveyed to a storage section. | 1 |
BACKGROUND OF THE INVENTION
The present invention relates generally to automatic, high-speed packaging machinery and, in particular, to a transfer conveyor assembly interfacing between a collator and either a polyfilm wrapping machine or an envelope stuffing machine.
With ever-increasing costs for direct mail advertising the charges for which are determined by the gross weight of the mailed literature, it becomes desirable to minimize the weight of the mailer within which the advertising literature is mailed. Heretofore, film wrapping equipment has been developed by Doboy Packaging Machinery, Inc. for appropriately enclosing the collated literature in a film envelope containing graphics that appropriately designates the addressor, addressee, as well as further advertising. The wrapper may also include transparent windows so as to highlight the contained literature. Collating equipment, such as the model A-297-6 manufactured and sold by the Phillipsburg Manufacturing Division of the Bell and Howell Corporation is available for appropriately arranging a number of pieces of literature to be mailed into separate stacks and which are later either manually or automatically stuffed into appropriate paper envelope. In that paper envelopes tend to be heavier than polyfilm wrappers, it is desirable that the collated material be wrapped in polyfilm in lieu of paper envelopes.
While the collator and polyfilm wrapping equipment have previously been developed, a problem has persisted in the development of a suitable assembly for interfacing between the above-mentioned equipment. The device coupling the collator to the wrapper should allow the option whereby the advertising matter may be appropriately film wrapped or, alternatively stuffed into a conventional paper envelopes without requiring extensive efforts to reconfigure the equipment. It is also necessary that a transfer assembly operate in synchronization with the associated collating and wrapping/stuffing equipment. Such synchronization becomes especially critical for a film wrapper, since in that case it is necessary that the collated matter be admitted relative to a preprinted and formed tube of polyfilm that is subsequently sealed and cut. If synchronization is not maintained, the printed matter is not properly aligned relative to the printed polyfilm and, thus, waste occurs. Also, it is necessary to maintain a high transfer rate without inducing curling or other disassembly of the collated and stacked matter.
These various objects are, however, achieved via the present transfer equipment which is comprised of a plurality of overlapping flights of chain drives, each having associated pushing members attached thereto for engaging the stacks of printed matter and transferring them at a controlled rate to the appropriate mailing wrapper. Synchronization is achieved between the collator and the transfer assembly by coupling collator drive to the transfer assembly and by initially spacing the pushing members of the primary transfer drive to accomodate the collation time of the stacks of printed matter.
The above objects, advantages and distinctions of the present equipment, as well as various others will, however, become more apparent upon reference to the following description thereof with respect to the following drawings. Before referring thereto, though, it is to be recognized that the following description is made only with respect to the presently preferred embodiment and, accordingly, various changes and modifications may be made thereto without departing from the spirit and scope of the present invention.
SUMMARY OF THE INVENTION
As already indicated, the present invention involves a transfer apparatus in combination with apparatus for collating a plurality of sheets of printed matter whereby the collated material is directed into an appropriate mailer, either a film wrapper or a paper wrapper. In accordance with the invention, the transfer assembly comprises a plurality of overlapping flights of chain drives, each having a plurality of pusher members attached to the chains for engaging and transferring the stacks of collated material from the collator to the wrapper. Synchronization between the collator and the film wrapper is achieved via the coupling of two interdependent continuous chain drives to an intermittent, clutch-coupled chain driven from the collator. Overlying retractable frame members ensure that the stacked materials do not become disturbed as they traverse the horizontal table through which various chain connected pushing members project.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a perspective view of the present transfer assembly relative to the collator, film wrapper and envelope stuffer.
FIG. 2 shows a top plan view of the overlapping chain drives relative to the horizontal slide bed.
FIG. 3 shows a front elevation view of the present transfer assembly.
FIG. 4 shows an end view taken along lines 4--4 of FIG. 3.
FIG. 5 shows an end view taken along lines 5--5 of FIG. 3.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to FIG. 1, a perspective view is shown of the present transfer assembly 2 illustrating its relative location with respect to a conventional collator 4 mounted at the right end of the assembly 2 and a high-speed film wrapping machine 6 mounted at the left end of the assembly. A paper envelope stuffing apparatus 8 is shown positioned to the front side thereof, near the collator. The collating apparatus may be of any suitable type, but, at present, it is contemplated to be a model A-297-6 collator manufactured and sold by the Phillipsburg Manufacturing Division of the Bell and Howell Corporation. Similarly, the high-speed film wrapping machine may be a Doboy Literature Wrapper manufactured by Doboy Packaging Machinery, Inc. of New Richmond, Wis. The side mounted envelope stuffer 8 is also manufactured by the Phillipsburg Manufacturing Division. Thus, the present invention comprises a transfer assembly 2 adapted to the collator 4, film wrapper 6 and envelope stuffer 8 for permitting the selective placement of the collated material into either a film mailer or a conventional paper envelope.
Associated with the transfer assembly 2 is a horizontal transfer table 10 that contains a plurality of drive regions 12, 14 and 16 wherein slots are cut through the table 10 to allow a plurality of pushing members to project and to sequentially engage and move the collated material at an appropriate rate of speed and in an appropriate direction, relative to the desired mailer packaging device. If it is desired to place the collated material into a paper mailer, the advertising material is conveyed from the collator 4 by the three-fingered pushing members 18 to the middle of the region 12, where an overlying side discharge assembly 19 (only a portion of which is shown) acts to jog the collated material to the front (when viewed in FIG. 1) and into the envelope stuffing equipment 8. The equipment 8, in turn, acts to individually fold, open and stuff paper envelopes with the collated material, before wetting an adhesive sealer and sealing the envelopes.
Alternatively, if it is desired to instead wrap the collated material with a film wrapper, the material is engaged by the fingers 18 and pushed to the end of region 12 where the fingers 20 of a two-fingered chain drive separately engage the stacks of material as they arrive and convey them to the end of region 14 where the fingers 22 of a two-fingered chain drive engage the stacked material and feeds it into the film wrapper 6. Since most typically the film wrapper 24 of the stock equipment 6 contains printed matter and windows therethrough so as to expose the addressor and addressee information, it is necessary that the transfer of the stacks of material be such that a bottleneck does not occur at the collator 4 nor at the wrapper 6 and that the material delivered to the wrapper 6 be at a rate that ensures that the printing of the film wrapper 24 aligns with the collated contents. Thus, it is necessary that the present chain drive assemblies associated with the pusher fingers 18, 20 and 22 be synchronized with the respective collator 4 and wrapper 6 and that it provide a continuous midregion 14 that is sufficiently long so as to accomodate the fastest intermittent rate of the collator 4 and the slowest continuous rate of the film wrapper 6. The details thereof will, however, be described below.
Further, because it is necessary to maintain the printed matter in a tightly packed pile, overlying hold-down carriages 26 and 28 are provided which extend over regions 12 and 14 and 16. The hold-down carriages 26 and 28 are hinged so that they may be rotated upwardly and away from the feedpath to facilitate access to the stacks of printed matter, should this be necessary during operation. As the material is transferred, it is necessary that the fingers 18, 20 and 22 not disrupt the stacks of printed materials, while jogging them into neat, aligned piles. In the present invention, this alignment is achieved by using a plurality of different pushing members 18, 20 and 22 which are transversely mounted relative to one another so as to each engage different portions of the stacks of material, thereby repetitively jogging the material into a uniform vertical alignment, before packaging. Overlying members 26a, 28a mounted to the carriages 26 and 28 at the pickup points also frictionally engage the stacks and hold the top sheets in registry.
Referring next to FIG. 2, a top view is shown of the present transfer assembly 2 with the carriages 26 and 28 and portions of the table 10 removed so as to expose the underlying chain drives and their associated pushing members and rider bars. With reference in FIG. 2 to the chain drive region 12, it begins in the collator 4 at an idler axle (not shown) mounted upstream of drive axle 30. It is to be recognized, however, that the unseen idler axle for the drive region 12 is substantially the same as drive axle 30 which is supported by a pair of end mounted bearings 31 between the frame side members 32 and 33. Depending upon the type of mailer (i.e. paper or film) that is desired, either drive axle 30 assists in conveying the collated materials to the envelope stuffer 8 or the unseen idler axle is used to assist in conveying the collated materials to the wrapper 6, instead. Specifically, where a paper envelope is to be used, the sprocket pair 34 and 36 are clamped to the axle 30 to the right of the position shown and are coupled via chains (not shown) to the collator 4 so as to convey and deposit the stacked materials in the region adjacent to the side discharge assembly 19. There the discharge arms (not shown) are intermittently actuated so as to engage the materials and push them to the front (FIG. 1) and into the infeed to the envelope stuffing apparatus 8.
Alternatively, where a polyfilm wrapper is desired, the sprockets 34 and 36 are moved over to the left (FIG. 2) and out of the way and are reclamped to axle 30. Longer drive chains 38, 40 and 42 are then added and mounted about the associated sprockets on the idler axle (not shown) and are, in turn, connected to the forwardly mounted sprocket pair 44 and single sprocket 46 that are mounted on axle 48. Axle 48 thus becomes the drive axle, rather than drive axle 30. Each of the chains 38, 40 and 42, in turn, contain a plurality of normally projecting pushing members 18, which are typically spaced apart from one another by approximately 12-1/2 inches. The outermost pushers are taller than the center pusher members so that they can convey the collated materials past the side discharge assembly 19 to the conveyor region 14.
Drive power for the transfer assembly 2 is, obtained from the same motor (not shown) which drives the collator 4 and which is mounted thereunder. In particular, the motor coupled by a timing belt to the collator's gear box which contains a Horton air clutch and, thence, via a plurality of sprockets and interconnecting chains, gear boxes and shafts to the mating sprockets of drive regions 12 and 14. The details of these connections will become more apparent from the following discussion. At the same time the motor of the collator drives a separate 90° gear transfer unit 43 and the wrapper 6 via an intermediate shaft 88 and a timing belt 45 that are coupled to the unit 43. The wrapper, in turn, provides power to the drive region 16 of the conveyor. Thus, upon disengaging the air clutch, the collator 4 and the drive regions 12 and 14 may be disengaged from the wrapper 6. This facilitates the synchronization of each to the other.
Referring to drive region 12, it obtains its power from the chain 51 (coupled to a sprocket intermediate the collator gear box and both of which are not shown) which, is coupled to the sprocket 52 mounted on axle 50. Axle 50 transfers the power to axle 48 via sprockets 49 and 53 and the chain 55 coupled therewith. Power is thus transferred from the collator 4 to drive region 12 and the pusher member containing chains 38, 40 and 42. At this point, it should be noted, too, that this power is applied intermittently as the stacks of material are shifted through the collator so that the pusher members 18 are able to pick up each stack, through the entire length of the collator. During the initial set up, the sprockets on the unseen idler axle (which are similar to sprockets 34 and on axle 30) are unclamped and rotated so as to cause the pusher members 18 to engage the stacks of material at collation stations before they are reclamped. Thus, as the pusher member 18 pass each collation station, one or more pieces of literature is added to the underlying stack until each complete collated stack reaches the end of the drive region 12.
Once each stack of collated material passes through the drive region 12, it reaches the beginning of the conveyor region 14. There the pushing members 20, coupled to the chains 60 and 62 which pass around the sprockets 54 mounted on axles 56 and 58, rise from below the table 10 and collect the collated materials and convey them at a continuous rate to the next conveyor region 16. The power to operate the continuous drive region 14 is obtained via the 90° gear drive assembly 64 that is mounted beneath the axle 56 and which receives its power from a driven line shaft 66 from the collator 4. The gear drive 64, in turn, transfers the power via its output shaft 68 to sprocket 70 and thence to axle 58 via chain 74 and sprocket 76.
As mentioned, the drive to axle 58 and drive region 14 is continuous, whereas that to axle 50 and drive region 12 is intermittent. It, therefore, is necessary to time the pusher members 20 relative to the members 18 to ensure the proper pick up of the collated materials. This is achieved via the trans-torque clutch 77 that is mounted in conjunction with the axle 58 at sprocket 76 and which provides the operator the ability to disengage the drive to the axle 58 so that the pusher members 20 may be adjusted so as to rise from below the table 10 and pick up the collated materials just as the members 18 fall.
At this point, it is also to be noted that the pusher members 20 are spaced approximately 20 inches apart along the chains 60 and 62 and are each pivotally mounted to the chains via an associated pivot pin. The pushing members 20 are maintained in their upright position as the chain travels over the rider bars 78, while they pivot and fall away from the stacked materials as they revolve around the sprockets 54 on axle 58. The pivoting of each of the members 20 is assured due to the boring of a relief hole in the metallic member 20 so that the weight is less on the forward end, thus causing the member 20 to pivot about a hollow pivot pin and away from the stacked materials.
As the materials are deposited at the drive region 16, a transversely mounted pair of pushing members 22 rise from beneath the transfer assembly frame and continue to convey the stacked materials to the film wrapper 6 at yet another rate (which may or may not be the same as for region 14). The motive power to the transfer assembly 2 in region 16 is provided to the drive axle 80 from the wrapper 6 chain 79 and which couples to sprocket 81. The power is, in turn, transferred to the pusher members 22 through the chains 82 and 84 and which pass over the sprockets 86. The chains 82 and 84 carry the pushing members 22 and the stacked materials over the rider bars 85 and, eventually, deposit the stacked materials at the infeed to the film wrapper 6 at the axle 80. The film wrapper 6 then picks up each stack of materials and feeds it into a formed tube of film 24 which is successively sealed on one longitudinal side and at the ends and after which the ends are cut so as to define an individual mailer. The details thereof will, however, not be described but should information with respect thereto be desired, it may be obtained by referring to the various sales literature descriptive thereof and which is available from the present assignee.
At this point, it should be noted that the correct positional relationship of the stacked materials to the film wrapper is achieved via the clutch 83. Specifically, the clutch 83 provides the operator with the ability to disengage axle 80 from the wrapper 6 drive power so that the pusher members 22 can be adjusted to fall, just as the infeed to wrapper 6 engages the collated materials. This then ensures that the materials are in alignment with the printing on the film wrapper 24.
As previously mentioned, the drive power to the film wrapper 6 is obtained from the timing belt 45 and its associated 90° gear transfer unit 43. In particular, the collator 4 drives the transfer unit 43 and it, in turn, transfers power to the wrapper 6 via the timing belt 45 and transfer shaft 88.
Directing attention now to FIG. 3, a front elevation view is shown of the transfer assembly 2 and the power coupling to the chain conveyors can more particularly be seen as well as the elevation of the various sprockets and the closed loop, endless paths of the chains. In the chain drive region 16, it can be seen that each of the chains 82 and 84 (although only chain 84 is shown) is looped about a plurality of sprockets and a roller. Specifically, the chain 84 is looped about the upper sprockets 86, a lower tensioning sprocket 90 and an intermediate roller 92 which coact to place a sufficient tension on the chain and to direct it so as to clear the various other structures of the present apparatus. The sprockets 86 mounted to axle 58 are also mounted on roller bearings, thereby isolating drive region 16 during the synchronizing of drive region 14, upon disengaging clutch 77.
Also seen in FIG. 3 is the right angle gear transfer unit 64 cooperating with chain 74 and axle 58. Mounted beneath the transfer unit 64 is the transfer unit 43 and its timing belt 45. The transfer unit 43 receives its drive power from the collator motor via a chain coupling (shown in phantom), while the transfer unit 64 receives power from a gear box (not shown) coupled to shaft 66. The drive to axle 50 comes from the chain 51 coupled to the collator 4 and a mating sprocket mounted (not shown) in the region beneath the envelope stuffer 8.
Directing attention next to FIG. 4, the sprockets 90, roller 92 and rider bars 85 can be seen relative to their mounting to the side frames 32 and 33 of the transfer assembly 2.
FIG. 5 shows the power transfer that takes place relative to axle 58 and sprockets 76 via the intervening sprokets 65 and 70, chain 71 and right angled power take off 64. The sprocket 65 essentially acts as an idler or clearance and tensioning sprocket as the power is conveyed to sprockets 76 and 54 via chain 74. The rider bars 78 upon which the chains 60 and 62 travel in a continuous fashion are also shown relative to the frame.
From the above description and the drawings depictive of the present invention, it should be apparent that various modifications may be made to the present power transfer assemblies so as to ensure that power is appropriately delivered to the various conveyor regions. Additionally, other modifications may be made, without departing from the spirit and scope of the present invention. It is, accordingly, contemplated that to the extent such equivalent embodiments fall within the spirit and scope of the following claims, they should be interpreted to include such embodiments therein. | Apparatus having a plurality of controlled overlapping chain drives, each chain drive containing a plurality of raised members for receiving collated stacks of mailing literature and conveying the literature over their successive paths in synchrony with a collating assembly to a film wrapping assembly coupled at the opposite end thereof. Independently hinged overlying hold-down assemblies prevent the collating material from curling or otherwise becoming disassembled before wrapping in a film wrapper or in a paper wrapper. | 1 |
BACKGROUND OF THE INVENTION
The use of ultrasonic energy for combining responsive materials in web-size widths, as in quilting, involves provision of a pattern roll for supporting the matrial being combined in relation to a series of sonic horns so that the ultrasonic energy is converted to heat at the output surfaces of the horns wherever the pattern roll acts as an opposing anvil. U.S. Pat. No. 3,733,238 illustrates and describes an arrangement of such apparatus. The pattern rolls heretofore available for use in apparatus of this sort have been formed by drilling the roll body to receive pin elements in a particular pattern. When pin elements are installed in this way, however, the process of roll formation is not only particularly tedious, but it is also difficult to maintain the pins at an even projecting height, and it is additionally difficult to secure the pins in place adequately for extended roll use because the sonic horn action generates a severe tendency to vibrate them loose.
The present invention eliminates these difficulties and further allows considerably greater pattern possibilities than prior practice has permitted.
SUMMARY OF THE INVENTION
According to the present invention a pattern roll for sonic horn opposition is formed by preparing a mill for a predetermined pattern of discrete horn opposing elements projecting from a base rib, applying the mill to a roll body for partially raising the pattern at the roll body surface, coating the partially raised pattern with a resist and etching the roll body to the base of the pattern rise, and then repeating the mill application and etching steps until the predetermined pattern is fully raised at the roll body surface.
The resulting pattern roll has the horn opposing elements and the base rib from which they project formed integrally with the roll body and at a regular height, and following the predetermined pattern both as to course of the base rib and cross-sectional shape and spacing of the horn opposing elements. Thus in the case of quilting or the like it is possible to shape the projecting elements and space them so that the fusing of interposed quilting material produces an exterior appearance that simulates stitching quite closely, or to produce other effects as desired. Also, the course of such apparent stitching can be made to follow a regular geometric design, based on a diamond for example, or a design that is highly fancy or that is adapted to outline ornamental figures, such as a flower, borne by the material being quilted. Additionally, the cross-sectional shape of the projecting elements may be varied at will to be circular or rectangular, or to have the shape of a diamond or a star, or a variety of other shapes as may be desired in particular instances.
These and other features of the present invention are described in further detail below in connection with the accompanying drawings listed below.
DESCRIPTION OF THE DRAWINGS
FIG. 1 is a fragmentary elevation indicating the general structure and operating disposition of a pattern roll embodying the present invention;
FIG. 2 is an enlarged detail of roll surface portion enclosed by the broken line circle in FIG. 1;
FIG. 3 is a sectional detail taken substantially at the line 3--3 in FIG. 2;
FIG. 4 is a plan view of a quilting pattern produced with the FIG. 1 pattern roll;
FIG. 5 is a sectional detail taken substantially at the line 5--5 in FIG. 4;
FIG. 6 is a plan view corresponding generally to FIG. 4 but showing a fancier quilting pattern such as is readily within the capability of pattern rolls formed according to the present invention;
FIG. 7 is an elevation of a mill such as is used in forming pattern rolls according to the present invention; and
FIG. 8 is a block diagram indicating the procedural sequence for forming pattern rolls according to the present invention.
DETAILED DESCRIPTION OF THE INVENTION
A pattern roll embodying the present invention is indicated at 10 in FIG. 1 as suitably comprising a tubular shell 12 fitted with end headers 14 at which stub shafts 16 are installed for journaling in pillow blocks as at 18 so that a pattern 20 raised at the surface of roll 10 may be disposed in opposition to sonic horns 22 to act on interposed material 24. A pulley drive 26 is provided to rotate roll 10 so that its opposing action takes place as the interposed material 24 travels between the roll and horns 22.
The nature of the pattern 20 raised at the surface of roll 10 is indicated representatively in FIGS. 2 and 3 as being formed by a continuous base rib 28 from which discrete horn opposing elements 30 project in spaced relation. A mill is used to raise the pattern 20, as will be noted further presently, and the mill provided for this purpose is preferably prepared for a widthwise repeat of the pattern involved at a width corresponding to that of the sonic horns 22 so that this pattern repeat can be raised on the roll 10 at lengthwise spacings opposing a repeat at each sonic horn. By such an arrangement the alignment of pattern elements within each repeat is maintained regularly, and proper tuning of the sonic horns is made easier.
The roll 10 bearing as many repeats of pattern 20 as are needed to process the material 24 being handled has the horn opposing elements 30 finished at an even projecting height and with a projecting face curvature concentric with the roll axis. In further particular, the horn opposing elements 30 taper from the base rib 28 at which they project and are limited in projecting height sufficiently for mill release during formation, while the base rib 28 is raised on the roll 10 sufficiently to provide an aggregate height of base rib and horn opposing elements sufficient to accommodate the interposed material 24 readily between the roll 10 and sonic horns 22. For example, in handling quilting of the sort illustrated in FIGS. 4 and 5 the pattern roll 10 employed was found with horn opposing elements 30 that projected 0.040 inch at a 0.015 inch taper from a base rib 28 that was raised sufficiently to provide an aggregate height of 0.090 inch.
FIGS. 4 and 5 illustrate a quilting produced with a pattern roll 10 of the form shown in FIGS. 1-3 from face and back plies 32 and 34 of 50/50 cotton-polyester fabric covering an interposed non-woven batt 36 of 100% polyester fiber. The effect of pattern roll 10 is to cause these responsive materials to fuse or bond or weld in the pattern of the horn opposing elements 30 as a result of the heat conversion thereat from the sonic horn action. The illustrated pattern roll 10 is formed to simulate stitching which appears in the quilting as indicated at 30'. FIG. 4 shows a full widthwise repeat centrally with partial repeats indicated at each side. The number of such repeats will, of course, depend on the desired width of the quilting being produced, and the pattern roll 10 will have as many repeats from lengthwise thereof as are needed for the quilting width desired. A common pattern roll arrangement is one formed with fifteen repeats, each about 81/2inches wide.
FIG. 6 illustrates the same sort of quilting bonded with a varied pattern of simulated stitching 30" such as may be formed with equal facility by a pattern roll embodying the present invention. Alternatively, if the covering face ply of the quilting is decorated with figures of any sort the bonding pattern can be arranged in relation to such figures so as to outline them for emphasis. Also, the bonding points are not limited to simulating stitching, but may have any cross-sectional form desired, as noted earlier. In short, the pattern roll arrangement can be made to follow a desired predetermined design as to course of base rib 28 and cross-sectional shape and spacing of the horn opposing elements 30 with wide flexibility.
A mill 38 of the sort employed for forming a pattern roll 10 corresponding to that shown in FIGS. 1-3 is illustrated in FIG. 7 as comprising a cylindrical body having journal portions 40 extending axially at each end and having a diameter allowing an exactly even multiple of the running pattern repeat to be formed in relief circumferentially thereof, while the axial length of the mill body is proportioned for a single widthwise repeat. In this case only a single running repeat of the pattern is formed, and, in addition to the pattern relief for the base rib 28 at 42 and for the horn opposing elements 30 at 44, central circumferential groove 46 and circumferential half grooves 48 at each end are formed in the mill body to raise corresponding ridges during pattern formation that aid in maintaining proper mill registration and in the final finishing of the roll. Upon preparation of the mill 38 in the foregoing form it is flame hardened for use. The mill 38 is suitably formed of 1018 carbon steel, as is the pattern roll 10.
To raise the pattern on roll 10 the mill 38 is applied thereto by mounting it for rotation in a fixture by which it can be brought to bear at the surface of roll 10 with the latter supported in a stand equipped with means for rotating the roll body. The diameter of the pattern roll body is checked at this time to determine whether it will accept an exactly even multiple of the running pattern repeat from the mill 38. As the blank roll body is purposely provided slightly oversize, some turning down will be necessary to fit the pattern repeat.
Once this has been done, enough pressure is exerted on the mill 38 to cause a partial raising of the pattern at the roll surface to the extent that the materials involved will allow. The mill 38 is then withdrawn and the partially raised pattern is coated with a resist, such as beeswax, and then etched to the base of the pattern rise. Thereafter the mill application and etching steps are sequentially repeated until the pattern has been fully raised at the roll surface. As the mill 38 is formed with only one widthwise repeat, the foregoing procedure must be duplicated for each such repeat required. Preferably the first repeat is raised at the lengthwise center of the roll and the additionally required ones alternately toward each end.
When all of the required widthwise repeats have been fully raised, the horn opposing elements 30 are abraded to an even projecting height and with a projecting face curvature concentric with the roll axis. For this purpose the elements 30 are raised about 0.010 inch beyond the final height desired and the abrading means is moved lengthwise of the roll while the roll is turned. During this step the circumferential ridges raised by the mill grooves 46 and 48, and to which resist has also been applied serve to stabilize the abrading means and thus facilitate the finishing of elements 30. After the abrading step the circumferential ridges are removed from the roll surface and the roll body is then chrome plated to improve its wear resistance and protect it against rusting during use.
Because the thus formed pattern roll has the pattern raised as an integral part thereof, it provides an excellent service life that is much improved over the rolls heretofore available for this purpose. Also, the pattern elements in each repeat are maintained in perfect alignment according to the present invention, and adjacent widthwise repeats are also readily aligned within acceptable limits.
The present invention has been described in detail above for purposes of illustration only and is not intended to be limited by this description or otherwise to exclude any variation or equivalent form or procedure that would be apparent from, or reasonably suggested by, the foregoing disclosure to the skill of the art. | A pattern roll is provided for use in opposition to a sonic horn for fusing responsive material interposed between the roll and horn. The pattern of the roll is formed integrally on the roll body in a manner that provides a much more serviceable roll and one in which the pattern possibilities are greatly increased in relation to pattern rolls of this sort heretofore available. | 1 |
This is a division, of application Ser. No. 925,157, filed July 17, 1978.
BACKGROUND OF THE INVENTION
(a) Field of the Invention
The present invention relates to electrophotographic sensitive materials, in particular novel sensitive materials which comprise a photosensitive layer containing a disazo pigment as an effective ingredient.
(b) Description of the Prior Art
As the electrophotographic sensitive material prepared by forming a photosensitive layer containing some azo pigment as an effective ingredient on a conductive support, one prepared by employing monoazo pigment (cf. Japanese Patent Publication No. 16474/1969), one prepared by employing benzidine-type disazo pigment (cf. U.S. Pat. No. 3,898,048 and U.S. Pat. No. 4,052,210), etc. are well known. These azo pigments are admittedly useful materials as an effective ingredient of the photosensitive layer as stated above, but when various requirements for photosensitive materials are taken into account from the viewpoint of the electrophotographic process, there has in fact not yet been obtained such a material as will sufficiently meet these requirements. Therefore, it is a matter of more importance to provide a wide variety of pigments, not limited to azo pigments, so as to afford a wide range of selection of pigments acting as an effective ingredient, thereby rendering it possible to provide a photosensitive material apposite to any specific process. In other words, it is desirable for the electrophotographic process that the variety of the pigments workable as an effective ingredient of photosensitive materials is as wide as possible.
SUMMARY OF THE INVENTION
A primary object of the present invention is to provide electrophotographic sensitive materials containing novel disazo pigments workable as an effective ingredient for a variety of electrophotographic processes.
A secondary object of the present invention is to provide electrophotographic sensitive materials which afford a wide range of selection of pigments workable as an effective ingredient.
Another object of the present invention is to provide electrophotographic sensitive materials having a high sensitivity as well as high flexibility and which contain the aforesaid disazo pigment.
In other words, the present invention provides electrophotographic sensitive materials characterized by having a photosensitive layer containing a disazo pigment, as an effective ingredient, which is selected from the group consisting disazo pigments expressed by the following general formulas I, II, III, and IV, ##STR3## [wherein A is selected from the group consisting of ##STR4## is selected from the group consisting of aromatic rings such as benzene ring, naphthalene ring, etc., hetero rings such as indole ring, carbazole ring, benzofuran ring, etc. and their substituents, Ar 1 is selected from the group consisting of aromatic rings such as benzene ring, naphthalene ring, etc., hetero rings such as dibenzofuran, etc. and their substituents, Ar 2 and Ar 3 are selected from the group consisting of aromatic rings such as benzene ring, naphthalene ring, etc. and their substituents, R 1 and R 3 are selected from the group consisting of hydrogen, lower alkyl radical or phenyl radical and their substituents and R 2 is selected from the group consisting of lower alkyl radical, carboxyl radical and their esters)].
Hereinafter are shown concrete examples of the compounds expressed by the foregoing general formula I by means of structural formula. ##STR5## The portion ##STR6## being common to Compounds No. 2A-66A, is omitted and is expressed as --Y 1 -- in short hereinafter. ##STR7##
The disazo pigments expressed by the general formula I can be easily prepared through the process comprising first diazotizing the starting material 2,7-diaminofluoren-9-one which is readily available commercially or in accordance with conventional methods to precipitate tetrazonium salt and thereafter effecting coupling reaction of this tetrazonium salt with a coupler, such as Naphthol AS, corresponding to the aforedescribed various pigments within an appropriate organic solvent such as N,N-dimethyl formamide in the presence of alkali. For instance, the process of preparing the pigment No. 1A is as described in the following. Further, other disazo pigments can also be prepared by applying the same process excepting for changing the material used.
Preparation Example
5.5 g of 2,7-diaminofluoren-9-one is added to a dilute hydrochloric acid consisting of 46 ml of concentrated hydrochloric acid and 46 ml of water, and same is well stirred at 60° C. for about 30 minutes. Next, this mixture is cooled to about 0° C., and a solution obtained by dissolving 3.8 g of sodium nitrite in 6 ml of water is added dropwise to said mixture at a temperature of 0°-5° C. for about 30 minutes. Then, the same is stirred at the same temperature for about 30 minutes, a small amount of unreacted matter is filtered, the filtrate is poured in 40 ml of 42% borofluoric acid, the so separated crystals are removed by filtration, washed with water and dried to obtain 7.4 g (yield 70%) of cream-colored crystals of bisdiazonium-bistetrafluoroborate. Next, the thus obtained 2 g of bisdiazonium salt and 2.9 g of 2-hydroxy-3-phenylcarbamoyl naphthalene as a coupler are dissolved in 425 ml of cooled -N,N-dimethylformamide, a solution consisting of 4.1 g of sodium acetate and 60 ml of water is added dropwise thereto at a temperature of 4°-8° C. for 1 hour, and the same is stirred at room temperature for about 3 hours. Thereafter, precipitates are removed by filtration, washed 3 times with 300 ml of water, and further washed 7 times with 300 ml of N,N-dimethylformamide. Still residual N,N-dimethylformamide is washed away with acetone, and thus obtained golden-colored crystals are dried at 70° C. under reduced pressure of 2 mmHg to obtain 3 g (the yield 80%) of disazo pigment No. 1A. The melting point is over 300° C.
______________________________________Elementary analysis (as C.sub.47 H.sub.30 N.sub.6 O.sub.5) Calculated value Observed value______________________________________C (%) 74.39 74.01H (%) 3.99 4.06N (%) 11.08 11.39______________________________________IR Absorption Spectrum (NBr tablet)1675 cm.sup.-1 (Secondary amide)1720 cm.sup.-1 (Carbonyl)______________________________________
Hereinafter will be shown concrete examples of compounds represented by the general formula II. ##STR8## The portion ##STR9## being common to Compounds No. 2B-66B, is omitted and represented as --Y 2 -- in short hereinafter. ##STR10##
The disazo pigments expressed by the general formula II can be easily prepared through the aforesaid process for preparing the disazo pigments expressed by the general formula I excepting the use of 3,7-diaminodibenzothiophene as the starting material. For instance, the process of preparing the pigment No. 1B is as described in the following. Further, other disazo pigments expressed by the general formula II can also be prepared in accordance with this preparation example excepting for changing the material used. Preparation Example
4.3 g of 3,7-diaminodibenzothiophene is added to a dilute hydrochloric acid consisting of 36 ml of concentrated hydrochloric acid and 36 ml of water, and same is well stirred at 60° C. for about 30 minutes. Next, this mixture is cooled to 0° C., and a solution obtained by dissolving 2.9 g of sodium nitrite in 10 ml of water is added dropwise to said mixture at a temperature of 0°-5° C. for about 30 minutes. Then, the same is stirred at the same temperature for about 30 minutes, a small amount of unreacted matter is filtrated, the filtrate is poured in 40 ml of 42% borofluoric acid, separated crystals are removed by filtration, washed with water and dried to obtain 80 g (the yield 98%) of yellow-colored crystals of bisdiazonium-distetrafluoroborate. The decomposition point is about 140° C. Next, the thus obtained 8.0 g bisdiazonium salt and 11.6 g of 2-hydroxy-3-phenylcarbamoyl naphthalene as a coupler are dissolved in 1.5 l of cooled N-N-dimethylformamide, a solution consisting of 16.4 g of sodium acetate and 160 ml of water is added dropwise thereto at a temperature of 4°-8° C. for 1 hour, and the same is stirred at room temperature for about 3 hours. Thereafter, precipitates are removed by filtration, washed 3 times with 500 ml of water, and further washed 8 times with 500 ml of N,N-dimethylformamide. Still residual N-N-dimethylformamide is washed away with acetone, and thus obtained pale and dark crystals are dried at 70° C. under reduced pressure of 2 mmHg to obtain 13.0 g (the yield 86%) of disazo pigment No. 1B. The melting point is over 300° C.
______________________________________Elementary analysis results (as C.sub.46 H.sub.30 N.sub.8 O.sub.4 S) Calculated value Observed value______________________________________C (%) 72.42 72.05H (%) 3.96 3.79N (%) 11.02 10.85IR Absorption Spectrum (KBr tablet)1680.sup.-1 (Secondary amide)______________________________________
Hereinafter will be shown concrete examples of compounds expressed by the general formula III. ##STR11## The portion ##STR12## being common to Compounds No. 2C-66C, is omitted and represented as --Y 3 -- in short hereinafter. ##STR13##
The portion ##STR14## being common to Compounds No. 68C-C, is omitted and represented as --Z-- in short hereinafter. ##STR15##
The disazo pigments expressed by the general formula III can be easily prepared through the aforesaid process for preparing the disazo pigments expressed by the general formula I excepting the use of diamino derivatives of the corresponding stilbene as the starting material. For instance, the process of preparing the aforesaid pigment No. 1C is as described in the following. Further, other disazo pigments expressed by the general formula III can also be prepared in accordance with this preparation example excepting for changing the material used.
Preparation Example 1.5 g of 2,2'-diaminostilbene is added to a dilute hydrochloric acid consisting of 12.6 ml of concentrated hydrochloric acid and 12.6 ml of water, and same is well stirred at 60° C. for about 30 minutes. Next, this mixture is cooled to about 0° C., and a solution obtained by dissolving 1.1 g of sodium nitrite in 1.7 ml of water is added dropwise to said mixture at a temperature of -1°˜0° C. for about 30 minutes. Then, the same is stirred at the same temperature for about 30 minutes, a small amount of unreacted matter is filtrated, the filtrate is poured in 11 ml of 42% borofluoric acid, the so separated crystals are removed by filtration, washed with water and dried to obtain 2.4 g (the yield 83%) of yellow-colored crystals of bisdiazonium-bistetrafluoroborate. The decomposition point is about 130° C.
Next, the thus obtained 2.0 g of bisdiazonium salt and 2.9 g of 2-hydroxy-3-phenylcarbamoylnaphthalene as a coupler are dissolved in 425 ml of cooled N,N-dimethylformamide, a solution consisting of 4.1 g of sodium acetate and 60 ml of water is added dropwise thereto at a temperature of 4°-8° C. for 1 hour, and then the same is stirred at room temperature for about 3 hours. Thereafter, precipitates are removed by filtration, washed 3 times with 300 ml of water, and further washed 8 times with 300 ml of N,N-dimethylformamide. Still residual N,N-dimethylformamide is washed away with acetone, and thus obtained pale and dark crystals are dried at 70° C. under reduced pressure of 2 mmHg to obtain 3.0 g (the yield 79%) of disazo pigment No. 1C. The melting point is over 300° C.
______________________________________Elementary analysis (as C.sub.48 H.sub.34 N.sub.6 O.sub.4) Calculated value Observed value______________________________________C (%) 75.97 75.53H (%) 4.52 4.32N (%) 11.08 10.80IR Absorption Spectrum (KBr tablet)1680 cm.sup.-1 (Secondary amide)______________________________________
Hereinafter will be shown concrete examples of compounds expressed by the general formula IV. ##STR16## The portion ##STR17## being common to Compounds No. 2D-66D, is omitted and represented as --Y 4 -- in short hereinafter. ##STR18##
The disazo pigments expressed by the general formula IV can be easily prepared through the aforesaid process for preparing the disazo pigment expressed by the general formula I excepting the use of 3,7-diaminodibenzothiophene-5,5-dioxide as the starting material. For instance, the process of preparing the aforesaid pigment No. 1D is as described in the following. Further, other disazo pigments expressed by the general formula IV can also be prepared in accordance with this preparation example excepting for changing the material used.
Preparation Example
1.3 g of 3,7-diaminodibenzothiophene-5,5-dioxide is added to a dilute hydrochloric acid consisting of 9 ml of concentrated hydrochloric acid and 9 ml of water, and same is well stirred at 80° C. for about 30 minutes. Next, this mixture is cooled to about 0° C., and a solution obtained by dissolving 0.8 g of sodium nitrite in 1 ml of water is added dropwise to said mixture at a temperature of 0°-5° C. for about 30 minutes. Then, the same is stirred at the same temperature for about 30 minutes, a small amount of unreacted matter is filtrated, the filtrate is poured in 10 ml of 42% borofluoric acid, the so separated crystals are removed by filtration, washed with water and dried to obtain 2.2 g (the yield 99%) of yellow-colored crystals of bisdiazoniumbistetrafluoroborate. The decomposition point is about 140° C. Next, the thus obtained 2.2 g of bisdiazonium salt and 2.9 g of 2-hydroxy-3-phenylcarbamoylnaphthalene as a coupler are dissolved in 425 ml of cooled, N,N-dimethylformamide, a solution consisting of 4.1 g of sodium acetate and 60 ml of water is added dropwise thereto at a temperature of 4°-8° C. for 1 hour, and then the same is stirred at room temperature for about 3 hours. Thereafter, precipitates are removed by filtration, washed 3 times with 300 ml of water, and further washed 8 times with 300 ml of N,N-dimethylformamide. Still residual N,N-dimethylformamide is washed away with acetone, and thus obtained pale and dark crystals are dried at 70° C. under reduced pressure of 2 mmHg to obtain 3.2 g (the yield 30%) of disazo pigment No. 1D. The melting point is over 300° C.
______________________________________Elementary analysis results (as C.sub.46 H.sub.30 N.sub.6 O.sub.6 S) Calculated value Observed value______________________________________ C (%) 69.51 68.95H (%) 3.80 3.79N (%) 10.57 10.85IR Absorption Spectrum (KBr tablet)1680 cm.sup.-1 (Secondary amide)______________________________________
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 through FIG. 4 illustrate, respectively, enlarged cross-sectional views of photosensitive materials according to the present invention.
Among the reference numerals in the drawings, 1 denotes a conductive support, 2, 2', 2" and 2'" denote respectively a photosensitive layer, 3 denotes a binder, 4 denotes a disazo compound, 5 denotes a charge-transfer medium, 6 denotes a charge-carrier generating layer, and 7 denotes a charge-transfer medium layer.
The photosensitive materials according to the present invention contain the above mentioned disazo pigments represented by the general formulas I, II, III and IV and can assume such structures as illustrated in FIGS. 1-4 according to the way of application of these pigments. The photosensitive material illustrated in FIG. 1 is one prepared by forming a disazo pigment 4 (which serves herein as a photoconductive substance)-resinous binder 3 type photosensitive layer 2 on a conductive support 1. The photosensitive material illustrated in FIG. 2 is one prepared by forming a disazo pigment 4 (which serves herein as a charge-carrier generating substance)-charge transfer medium (which is a mixture of charge-transfer substance and a resinous binder) 5 type photosensitive layer 2' on a conductive support 1. And the photosensitive materials illustrated in FIGS. 3-4 are modifications of the photosensitive material illustrated in FIG. 2 and the photosensitive layers 2" and 2'" are each composed of a charge-carrier generating layer 6 consisting essentially of the disazo pigment 4 and a charge-transfer medium layer 7. The respective ingredients of these photosensitive materials are supposed to assume such function and mechanism as mentioned hereinafter.
First, in the photosensitive material of FIG. 1, the disazo pigment acts as a photoconductive substance, and generation and transfer of the charge-carrier necessary for light decay is performed through the pigment particles. In the case of the photosensitive material of FIG. 2, the charge-transfer substance forms a charge-transfer medium together with the binder (plus a plasticizer as occasion demands), while the disazo pigment acts as a charge-carrier generating substance. This charge-transfer medium has no charge-carrier generating ability as disazo pigments do, but it has an ability to accept and transfer the charge-carrier generated by disazo pigments. That is, in the case of the photosensitive material of FIG. 2, generation of the charge-carrier necessary for light decay is performed by the disazo pigment, while transfer of the charge-carrier is performed mainly by the charge-transfer medium. An additional essential condition required for the charge-transfer medium on this occasion is that the scope of absorption wavelength of the charge-transfer medium should not fall on mainly the scope of absorption wavelength of the visible region of the disazo pigment. The reason for this is that it is necessary to transmit the light to the surface of the disazo pigment in order to generate the charge carrier efficiently in the said pigment. This, however, is not applicable to the case of, for instance, a photosensitive material which is sensitive only to a specific wavelength. Therefore, it will do if the absorption wavelengths of both the charge-transfer medium and the disazo pigment do not completely overlap each other. Next, in the case of the photosensitive material of FIG. 3, the light after passing through the charge-transfer medium layer reaches to the photosensitive layer 2" which acts as a charge-carrier generating layer, whereby generation of the charge-carrier is performed by the disazo pigment present in the portion, while the charge-transfer medium layer accepts the charge-carrier poured therein and transfers. The mechanism of this photosensitive material that generation of the charge-carrier required for light decay is performed by the disazo pigment and transfer of the charge-carrier is performed by the charge-transfer medium is the same as in the case of the photosensitive material illustrated in FIG. 2. The disazo pigment herein is likewise a charge-carrier generating substance. In this regard it is to be noted that the operation mechanism of the charge-transfer medium and charge-carrier generating layer in the photosensitive material of FIG. 4 is the same as in the case of the photosensitive material of FIG. 3.
In order to prepare the photosensitive material of FIG. 1, it suffices to coat a conductive support with a dispersion obtained by dispersing fine particles of a disazo pigment in a binder solution and then dry. In order to prepare the photosensitive material of FIG. 2, it suffices to disperse fine particles of a disazo pigment in a solution dissolved a charge-transfer substance and a binder therein, coat a conductive support with the resulting dispersion and then dry. And the photosensitive material of FIG. 3 can be obtained either by depositing a disazo pigment on a conductive support through vacuum evaporation or through the procedure comprising dispersing fine particles of a disazo pigment in an appropriate solvent dissolved a binder therein as occasion demands, coating the resulting dispersion on a conductive support and then drying and if further required, subjecting the thus formed photosensitive layer to the surface finishing, for instance, such as puff-grinding or the like or adjust the thickness of the coating film, thereafter coating thereon a solution containing a charge-transfer substance and a binder and drying. In this regard it is to be noted that in the case of the photosensitive material of FIG. 4 it can be obtained according to the procedure of preparing the photosensitive material of FIG. 3 wherein the order of forming the layers is reversed. In any case, the disazo pigment for use in the present invention is employed upon being pulverized into a particle size of less than 5μ, preferably less than 2μ, by means of a ball-mill or the like. Coating is effected using the conventional means such as doctor blade, wire bar, etc. The thickness of the photosensitive layers illustrated in FIGS. 1 and 2 is about 3-50μ, preferably 5-20μ. In the case of the photosensitive materials illustrated in FIGS. 3 and 4 the thickness of the charge-carrier generating layer is less than 5μ, preferably less than 2μ, and the thickness of the charge-transfer medium layer is about 3-50μ, preferably 5-20μ. In the case of the photosensitive material illustrated in FIG. 1, the proper amount of the disazo pigment contained in the photosensitive layer is 30-70% by weight, preferably about 50% by weight based on the weight of the photosensitive layer. (As above-described, in the case of the photosensitive material of FIG. 1 the disazo pigment acts as a photoconductive substance, and generation and transfer of the charge carrier required for light decay are performed through the pigment particles. Therefore, it is desirable that the contact between the pigment particles should be continuous from the photosensitive layer surface to the support. In view of this, it is desirable that the ratio of the disazo pigment to the photosensitive layer is as high as possible, but when taking both the strength and the sensitivity of the photosensitive layer into consideration, preferably it is about 50% by weight.) In the case of the photosensitive material illustrated in FIG. 2, the proper amount of the disazo pigment contained in the photosensitive layer is 1-50% by weight, preferably less than 20% by weight, and the proper amount of the charge-transfer substance therein is 10-95% by weight, preferably 30-90% by weight. And in the case of the photosensitive materials illustrated in FIGS. 3-4 the amount of the charge-transfer substance contained in the charge-transfer medium layer is 10-95% by weight, preferably 30-90% by weight as in the case of the photosensitive layer of the photosensitive material illustrated in FIG. 2. Further, in preparing all the photosensitive materials illustrated in FIGS. 1-4, it is possible to employ some plasticizer in combination with the binder.
In the photosensitive materials of the present invention there can be employed, as the conductive support, a plate or foil of a metal such as aluminum, etc., a plastic film deposited thereon a metal such as aluminum, etc. through vacuum evaporation, or a paper processed for conductivity. As binders suitably employed in the present invention, there are enumerated such condensation resins such as polyamide, polyurethane, polyester, epoxide resin, polyketone, polycarbonate, etc., vinyl polymers such as polyvinyl ketone, polystyrene, poly-N-vinyl carbazole, polyacrylamide, etc., and the like, but in spite of this, resins which are insulating and adhesive are all employable. As available plasticizers there can be enumerated halogenated paraffin, polyvinyl chloride, dimethyl naphthalene, dibutyl phthalate, etc. And as available charge-transfer substances there can be enumerated, as high molecular substances, vinyl polymers such as poly-N-vinyl carbazole, halogenated poly-N-vinyl carbazole, polyvinyl pyrene, polyvinyl indroquinoxaline, polyvinyl dibenzothiophene, polyvinyl anthracene, polyvinyl acridine, etc. and condensation resins such as pyrene-formaldehyde resin, bromopyrene-formaldehyde resin, ethyl carbazole-formaldehyde resin, chloroethyl carbazole-formaldehyde resin, etc., and as low molecular substances (monomers), fluorenone, 2-nitro-9-fluorenone, 2,7-dinitro-9-fluorenone, 2,4,7-trinitro-9-fluorenone, 2,4,5,7-tetranitro-9-fluorenone, 4H-indeno[1,2-b]thiophen-4-one, 2-nitro-4H-indeno[1,2-b]thiophen-4-one, 2,6,8-trinitro-4H-indeno[1,2-b]thiophen-4-one, 8H-indeno[2,1-b]thiophen-8-one, 2-intro-8H-indeno[2,1-b]thiophen-8-one, 2-bromo-6,8-dinitro-4H-indeno[1,2-b]thiophene, 6,8-dinitro-4H-indeno[1,2-b]thiophene, 2-nitrodibenzothiophene, 2,8-dinitrodibenzothiophene, 3-nitrodibenzothiophene-5-oxide, 3,7-dinitrodibenzothiophene-5-oxide, 1,3,7-trinitrodibenzothiophene-5,5-dioxide, 3-nitro-dibenzothiophene-5,5-dioxide, 3,7-dinitro-dibenzothiophene-5,5-dioxide, 4-dicyanomethylene-4H-indeno[1,2-b]thiophene, 6,8-dinitro-4-dicyanomethylene-4H-indeno[1,2-b]thiophene, 1,3,7,9-tetranitrobenzo[c]cinnoline-5-oxide, 2,4,10-trinitrobenzo[c]cinnoline-6-oxide, 2,4,8-trinitrobenzo[c]cinnoline-6-oxide, 2,4,8-trinitrothioxanthone, 2,4,7-trinitro-9,10-phenanthrene-guinone, 1,4-naphthoquinone-benzo[a]anthracene-7,12-dione, 2,4,7-trinitro-9-dicyanomethylene fluorene, tetrachlorophthalic anhydride, 1-bromopyrene, 1-methylpyrene, 1-ethylpyrene, 1-acetylpyrene, carbazole, N-ethylcarbazole, N-β-chloroethylcarbazole, N-β-hydroxyethyl carbazole, 2-phenyl indole, 2-phenylnaphthalene, 2,5-bis(4-diethylaminophenyl)-1,3,4-oxadiazole, 2,5-bis(4-diethylaminophenyl)-1,3,4-triazole, 1-phenyl-3-(4-diethylaminostyryl)-5-(4-diethylaminophenyl)pyrazoline, 2-phenyl-4-(4-diethylaminophenyl)-5-phenyloxazole, triphenyl amine, tris(4-diethylaminophenyl)methane, 3,6-bis(dibenzylamino)-9-ethyl carbazole, etc. These charge-transfer substances are employed either singly or in a combination of two or more of them.
Further, in every photosensitive material thus prepared an adhesive layer or a barrier layer can be disposed in between the conductive support and the photosensitive layer as occasion demands. The material suitably used in the formation of aforesaid layers includes polyamide, nitrocellulose, aluminum oxide, etc. and preferably the thickness of the layers is less than 1μ.
Reproduction using the photosensitive material according to the present invention can be achieved through the procedure comprising electrifying the photosensitive layer side of the photosensitive material, exposing and then developing, and if necessary, transferring onto an ordinary paper or the like.
The photosensitive materials according to the present invention have excellent advantages in that they are generally of high sensitivity and rich in flexibility.
DESCRIPTION OF PREFERRED EMBODIMENTS
Example 1
1 part by weight of polyester resin (namely, Polyester Adhesive 49000, the manufacture of Du Pont Inc.), 1 part by weight of the disazo compound No. 1A and 26 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was dried at a temperature of 100° C. for 10 minutes, whereby there was obtained a photosensitive material having a 7μ-thick photosensitive layer and a structure illustrated in FIG. 1.
Subsequently, after charging positive electricity on the photosensitive layer of this photosensitive material by applying +6 KV corona discharge for 20 seconds by means of a commercial electrostatic copying paper testing apparatus, the photosensitive material was left alone in the dark for 20 seconds, and the surface potential Vpo(volt) at the time was measured. Next, light was applied to the photosensitive layer by means of a tungsten lamp so as to attain the illumination of 20 luxes on the surface thereof, and the time (unit:second) required for reducing said surface potential Vpo to half was sought, whereby the amount of exposure E1/2 (lux.sec.) was obtained. The result was as follows:
Vpo=590 V, E1/2=15 lux.sec.
Examples 2 through 10
Varieties of photosensitive materials were prepared by applying the same procedure as in Example 1 save for employing the respective disazo compounds referred to by number in the following Table-1 in place of the disazo compound No. 1A used in Example 1. When these photosensitive materials were subsequently subjected to the same measurement of Vpo and E1/2 as in Example 1, the result was as shown in Table-1, respectively.
TABLE-1______________________________________ DisazoExample compound Vpo El/2No. No. (volt) (lux . sec.)______________________________________2 4A 630 83 17A 800 54 18A 700 155 32A 710 196 37A 725 307 49A 680 218 58A 695 259 62A 710 2510 65A 800 30______________________________________
Example 11
10 parts by weight of polyester resin (the same as that in Example 1), 10 parts by weight of 2,4,7-trinitro-9-fluorenone, 2 parts by weight of disazo compound No. 1A and 198 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was dried at a temperature of 100° C. for 10 minutes, whereby there was obtained a photosensitive material having a 10μ-thick photosensitive layer and a structure illustrated in FIG. 2. Subsequently, measurement of Vpo and E1/2 of this photosensitive material was conducted through the same procedure as in Example 1 save for applying -6 KV corona discharge instead of +6 KV corona discharge employed in Example 1. The result was as follows:
Vpo=450 V, E1/2=10 lux.sec.
Examples 12 through 20
Varieties of photosensitive materials having a structure illustrated in FIG. 2 were prepared by applying the same procedure as in Example 11 save for employing the respective disazo compounds referred to by number in the following Table-2 in place of the disazo compound No. 1A used in Example 11. When these photosensitive materials were subsequently subjected to the same measurement of Vpo and E1/2 as in Example 11, the result was as shown in Table-2, respectively.
TABLE-2______________________________________ DisazoExample compound Vpo El/2No. No. (volt) (lux . sec.)______________________________________12 3A 480 1013 5A 520 1514 11A 450 2015 23A 500 1516 25A 500 1517 35A 450 1018 38A 480 2019 41A 600 2020 60A 750 25______________________________________
Example 21
10 parts by weight of polyester resin (the same as that in Example 1), 10 parts by weight of 2,5-bis(4-diethylaminophenyl)-1,3,4-oxadiazole, 2 parts by weight of the disazo compound No. 1A and 198 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was dried at a temperature of 120° C. for 10 minutes, whereby there was prepared a photosensitive material having a 10μ-thick photosensitive layer and a structure illustrated in FIG. 2. When this photosensitive material was subsequently subjected to the same measurement as in Example 1, the result was as follows:
Vpo=830 V, E1/2=10 lux.sec.
Examples 22 through 30
Varieties of photosensitive materials having a structure illustrated in FIG. 2 were prepared by applying the same procedure as in Example 21 save for employing the respective disazo compounds referred to by number in the following Table-3 in place of the disazo compound No. 1A used in Example 21. When these photosensitive materials were subsequently subjected to the same measurement of Vpo and E1/2 as in Example 1, the result was as shown in the following Table-3, respectively.
TABLE-3______________________________________ DisazoExample compound Vpo El/2No. No. (volt) (lux . sec.)______________________________________22 2A 900 1523 9A 850 1824 13A 880 1625 28A 800 926 33A 900 1527 45A 820 1728 47A 930 1029 52A 950 1530 66A 910 20______________________________________
Example 31
200 parts by weight of poly-N-vinyl carbazole, 33 parts by weight of 2,4,7-trinitro-9-fluorenone, 20 parts by weight of polyester resin (the same as that in Example 1) and 20 parts by weight of the disazo compound No. 1A as added to 1780 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was dried at a temperature of 100° C. for 10 minutes and at a temperature of 120° C. for 5 minutes in succession, whereby there was obtained a photosensitive material having a 13μ-thick photosensitive layer and a structure illustrated in FIG. 2. When this photosensitive material was subjected to the same measurement as in Example 1, the result was as follows:
Vpo=1,035 V, E1/2=5 lux.sec.
Examples 32 through 40
Varieties of photosensitive materials having a structure illustrated in FIG. 2 were prepared by applying the same procedure as in Example 31 save for employing the respective disazo compound referred to by number in the following Table-4 in place of the disazo compound No. 1A used in Example 31. When these photosensitive materials were subsequently subjected to the same measurement of Vpo and E1/2 as in Example 1, the result was as shown in the following Table-4, respectively.
TABLE-4______________________________________ DisazoExample compound Vpo El/2No. No. (volt) (lux . sec.)______________________________________32 9A 1035 633 10A 1040 734 17A 1100 735 29A 1100 836 40A 1150 537 42A 1200 1538 51A 1280 1039 63A 1430 1940 64A 1500 15______________________________________
Example 41
2 parts by weight of the disazo compound No. 1A and 98 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was subjected to natural drying, whereby there was formed a 1μ-thick charge-carrier generating layer. Meanwhile, another dispersion was prepared by mixing 2 parts by weight of 2,4,7-trinitro-9-fluorenone, 2 parts by weight of polycarbonate (namely, Panlite L, the manufacture of TEIJIN Co., Ltd.) and 46 parts by weight of tetrahydrofuran together, and this dispersion was coated on the foregoing charge-carrier generating layer by means of a doctor blade and then dried at a temperature of 100° C. for 10 minutes to form a 10μ-thick charge-transfer medium layer, whereby there was obtained a photosensitive material having a structure illustrated in FIG. 3. When the thus obtained photosensitive material was subjected to the same measurement as in Example 1, the result was as follows:
Vpo=850 V, E1/2=15 lux.sec.
Examples 42 through 50
Varieties of photosensitive materials having a structure illustrated in FIG. 3 were prepared by applying the same procedure as in Example 41 save for employing the respective disazo compounds referred to by number in the following Table-5 in place of the disazo compound No. 1A used in Example 41. When these photosensitive materials were subjected to the same measurement of Vpo and E1/2 as in Example 1, the result was as shown in Table-5, respectively.
TABLE-5______________________________________ DisazoExample compound Vpo E1/2-No. No. (volt) (lux .______________________________________ sec.)42 8A 850 943 15A 880 1044 21A 880 1045 30A 870 846 33A 870 947 43A 855 1048 53A 865 1049 55A 880 1550 61A 880 15______________________________________
Example 51
2 parts by weight of the disazo compound No. 1A and 98 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was subjected to natural drying, whereby there was formed a 1μ-thick charge-carrier generating layer. Meanwhile, another dispersion was prepared by mixing 2 parts by weight of 2,5-bis(4-diethylaminophenyl)-1,3,4-oxadiazole, 2 parts by weight of polycarbonate (the same as that in Example 41) and 46 parts by weight of tetrahydrofuran together, and this dispersion was coated on the foregoing charge-carrier generating layer by means of a doctor blade and then dried at a temperature of 120° C. for 10 minutes to form a 10μ-thick charge-transfer medium layer, whereby there was obtained a laminate-type photosensitive material illustrated in FIG. 3. When the thus obtained photosensitive material was subjected to the same measurement of Vpo and E1/2 as in Example 1 save for applying -6 KV corona discharge instead of +6 KV corona discharge, the result was as follows:
Vpo=1,000 V, E1/2=8 lux.sec.
Examples 52 through 60
Varieties of photosensitive materials having the same structure as that of Example 51 were prepared by employing the respective disazo compound referred to by number in the following Table-6 in place of the disazo compound No. 1A used in Example 51. When these photosensitive materials were subjected to the same measurement of Vpo and E1/2 as in Example 1, the result was as shown in Table-6, respectively.
TABLE-6______________________________________ DisazoExample compound Vpo E1/2No. No. (volt) (lux.sec.)______________________________________52 6A 1000 553 14A 950 854 19A 980 555 22A 990 756 27A 990 957 36A 1020 1058 44A 990 1259 48A 1000 1560 53A 1100 20______________________________________
Example 61
1 part by weight of polyester resin (namely, Polyester Adhesive 49000, the manufacture of Du Pont Inc.), 1 part by weight of the disazo compound No. 1B and 26 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was dried at a temperature of 100° C. for 10 minutes, whereby there was obtained a photosensitive material having a 7μ-thick photosensitive layer and a structure illustrated in FIG. 1.
Subsequently, after charging positive electricity on the photosensitive layer of this photosensitive material by applying +6 KV corona discharge for 20 seconds by means of a commercial electrostatic copying paper testing apparatus, the photosensitive material was left alone in the dark for 20 seconds, and the surface potential Vpo(volt) at that time was measured. Next, light was applied to the photosensitive layer by means of a tungsten lamp so as to attain the illumination of 20 luxes on the surface thereof, and the time (unit:second) required for reducing said surface potential Vpo to half was sought, whereby the amount of exposure E1/2 (lux.sec.) was obtained. The result was as follows:
Vpo=500 V, E1/2=12 lux.sec.
Examples 62 through 70
Varieties of photosensitive materials were prepared by applying the same procedure as in Example 61 save for employing the respective disazo compounds referred to by number in the following Table-7 in place of the disazo compound No. 1B used in Example 61. When these photosensitive materials were subsequently subjected to the same measurement of Vpo and E1/2 as in Example 61, the result was as shown in Table-7, respectively.
TABLE-7______________________________________ DisazoExample compound Vpo E1/2No. No. (volt) (lux . sec.)______________________________________62 4B 620 1063 17B 600 1264 18B 680 1065 32B 620 1566 37B 630 2067 49B 690 1968 58B 680 2569 62B 680 2570 65B 690 30______________________________________
Example 71
10 parts by weight of polyester resin (the same as that in Example 61), 10 parts by weight of 2,4,7-trinitro-9-fluorenone, 2 parts by weight of disazo compound No. 1B and 198 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was dried at a temperature of 100° C. for 10 minutes, whereby there was obtained a photosensitive material having a 10μ-thick photosensitive layer and a structure illustrated in FIG. 2. Subsequently, measurement of Vpo and E1/2 of this photosensitive material was conducted through the same procedure as in Example 61 save for applying -6 KV corona discharge instead of +6 KV corona discharge employed in Example 61. The result was as follows:
Vpo=520 V, E1/2=9 lux.sec.
Examples 72 through 80
Varieties of photosensitive materials having a structure illustrated in FIG. 2 were prepared by applying the same procedure as in Example 71 save for employing the respective disazo compounds referred to by number in the following Table-8 in place of the disazo compound No. 1B used in Example 71. When these photosensitive materials were subsequently subjected to the same measurement of Vpo and E1/2 as in Example 61, the result was as shown in Table-8, respectively.
TABLE-8______________________________________ DisazoExample compound Vpo E1/2No. No. (volt) (lux.sec.)______________________________________72 3B 480 1073 5B 500 1074 11B 480 1275 23B 500 976 25B 500 1577 35B 490 1578 38B 520 1579 41B 500 2080 60B 580 18______________________________________
Example 81
10 parts by weight of polyester resin (the same as that in Example 61), 10 parts by weight of 2,5-bis(4-diethylaminophenyl)-1,3,4-oxadiazole, 2 parts by weight of the disazo compound No. 1B and 198 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was dried at a temperature of 120° C. for 10 minutes, whereby there was prepared a photosensitive material having a 10μ-thick photosensitive layer and a structure illustrated in FIG. 2. When this photosensitive material was subsequently subjected to the same measurement as in Example 61, the result was as follows:
Vpo=790 V, E1/2=5 lux.sec.
Examples 82 through 90
Varieties of photosensitive materials having a structure illustrated in FIG. 2 were prepared by applying the same procedure as in Example 81 save for employing the respective disazo compounds referred to by number in the following Table-9 in place of the disazo compound No. 1B used in Example 81. When these photosensitive materials were subsequently subjected to the same measurement of Vpo and E1/2 as in Example 61, the result was as shown in the following Table-9, respectively.
TABLE-9______________________________________ DisazoExample compound Vpo E1/2No. No. (volt) (lux.sec.)______________________________________82 2B 950 1083 9B 920 1284 13B 900 1085 28B 920 1586 33B 900 1387 45B 920 1988 47B 990 1989 52B 1000 2090 66B 950 25______________________________________
Example 91
200 parts by weight of poly-N-vinyl carbazole, 33 parts by weight of 2,4,7-trinitro-9-fluorenone, 20 parts by weight of polyester resin (the same as that in Example 61) and 20 parts by weight of the disazo compound No. 1B as added to 1780 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was dried at a temperature of 100° C. for 10 minutes and at a temperature of 120° C. for 5 minutes in succession, whereby there was obtained a photosensitive material having a 13μ-thick photosensitive layer and a structure illustrated in FIG. 2. When this photosensitive material was subjected to the same measurement as in Example 61, the result was as follows:
Vpo=1,020 V, E1/2=3 lux.sec.
Examples 92 through 100
Varieties of photosensitive materials having a structure illustrated in FIG. 2 were prepared by applying the same procedure as in Example 91 save for employing the respective disazo compound referred to by number in the following Table-10 in place of the disazo compound No. 1B used in Example 91. When these photosensitive materials were subsequently subjected to the same measurement of Vpo and E1/2 as in Example 61, the result was as shown in the following Table-10, respectively.
TABLE 10______________________________________ DisazoExample compound Vpo El/2No. No. (volt) (lux . sec.)______________________________________92 9B 1020 593 10B 1000 394 17B 1120 595 29B 1100 596 40B 980 897 42B 1000 1098 51B 1100 1299 63B 1000 15100 64B 1100 20______________________________________
Example 101
2 parts by weight of the disazo compound No. 1B and 98 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was subjected to natural drying, whereby there was formed a 1μ-thick charge-carrier generating layer. Meanwhile, another dispersion was prepared by mixing 2 parts by weight of 2,4,7-trinitro-9-fluorenone, 2 parts by weight of polycarbonate (namely, Panlite L, the manufacture of TEIJIN Co. Ltd.) and 46 parts by weight of tetrahydrofuran together, and this dispersion was coated on the foregoing charge-carrier generating layer by means of a doctor blade and then dried at a temperature of 100° C. for 10 minutes to form a 10μ-thick charge-transfer medium layer, whereby there was obtained a photosensitive material having a structure illustrated in FIG. 3. When the thus obtained photosensitive material was subjected to the same measurement as in Example 61, the result was as follows:
Vpo=900 V, E1/2=15 lux.sec.
Examples 102 through 110
Varieties of photosensitive materials having a structure illustrated in FIG. 3 were prepared by applying the same procedure as in Example 101 save for employing the respective disazo compounds referred to by number in the following Table-11 in place of the disazo compound No. 1B used in Example 101. When these photosensitive materials were subjected to the same measurement of Vpo and E1/2 as in Example 61, the result was as shown in Table-11, respectively.
TABLE 11______________________________________ DisazoExample compound Vpo El/2No. No. (volt) (lux . sec.)______________________________________102 8B 800 10103 15B 820 10104 21B 870 12105 30B 900 15106 33B 910 18107 43B 880 20108 53B 900 15109 55B 920 20110 61B 900 20______________________________________
Example 111
2 parts by weight of the disazo compound No. 1B and 98 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was subjected to natural drying, whereby there was formed a 1μ-thick charge-carrier generating layer. Meanwhile, another dispersion was prepared by mixing 2 parts by weight of 2,5-bis(4-diethylaminophenyl)-1,3,4-oxadiazole, 2 parts by weight of polycarbonate (the same as that in Example 101) and 46 parts by weight of tetrahydrofuran together, and this dispersion was coated on the foregoing charge-carrier generating layer by means of a doctor blade and then dried at a temperature of 120° C. for 10 minutes to form a 10μ-thick charge-transfer medium layer, whereby there was obtained a laminate-type photosensitive material illustrated in FIG. 3. When the thus obtained photosensitive material was subjected to the same measurement of Vpo and E1/2 as in Example 61 save for applying -6 KV corona discharge instead of +6 KV corona discharge, the result was as follows:
Vpo=1,020 V, E1/2=10 lux.sec.
Examples 112 through 120
Varieties of photosensitive materials having the same structure as that of Example 111 were prepared by employing the respective disazo compound referred to by number in the following Table-12 in place of the disazo compound No. 1B used in Example 111. When these photosensitive materials were subjected to the same measurement of Vpo and E1/2 as in Example 61, the result was as shown in Table-12, respectively.
TABLE 12______________________________________ DisazoExample compound Vpo E1/2No. No. (volt) (lux . sec.)______________________________________112 6B 1000 9113 14B 990 10114 19B 980 8115 22B 1000 12116 27B 1020 15117 36B 1030 10118 44B 1000 9119 48B 1100 20120 53B 1200 25______________________________________
Example 121
1 part by weight of polyester resin (namely, Polyester Adhesive 49000, the manufacture of Du Pont Inc.), 1 part by weight of the disazo compound No. 1C and 26 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was dried at a temperature of 100° C. for 10 minutes, whereby there was obtained a photosensitive material having a 7μ-thick photosensitive layer and a structure illustrated in FIG. 1.
Subsequently, after charging positive electricity on the photosensitive layer of this photosensitive material by applying +6 KV corona discharge for 20 seconds by means of a commercial electrostatic copying paper testing apparatus, the photosensitive material was left alone in the dark for 20 seconds, and the surface potential Vpo(volt) at that time was measured. Next, light was applied to the photosensitive layer by means of a tungsten lamp so as to attain the illumination of 20 luxes on the surface thereof, and the time (unit: second) required for reducing said surface potential Vpo to half was sought, whereby the amount of exposure E1/2 (lux.sec.) was obtained. The result was as follows:
Vpo=700 V, E1/2=10 lux.sec.
Examples 122 through 130
Varieties of photosensitive materials were prepared by applying the same procedure as in Example 121 save for employing the respective disazo compounds referred to by number in the following Table-13 in place of the disazo compound No. 1C used in Example 121. When these photosensitive materials were subsequently subjected to the same measurement of Vpo and E1/2 as in Example 121, the result was as shown in Table-13, respectively.
TABLE 13______________________________________ DisazoExample compound Vpo E1/2No. No. (volt) (lux . sec.)______________________________________122 3C 720 10123 5C 700 8124 18C 680 10125 30C 700 12126 44C 800 15127 49C 890 10128 55C 800 20129 67C 800 10130 93C 790 5______________________________________
Example 131
10 parts by weight of polyester resin (the same as that in Example 121), 10 parts by weight of 2,4,7-trinitro-9-fluorenone, 2 parts by weight of disazo compound No. 1C and 198 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was dried at a temperature of 100° C. for 10 minutes, whereby there was obtained a photosensitive material having a 10μ-thick photosensitive layer and a structure illustrated in FIG. 2. Subsequently, measurement of Vpo and E1/2 of this photosensitive material was conducted through the same procedure as in Example 121 save for applying -6 KV corona discharge instead of +6 KV corona discharge employed in Example 121. The result was as follows:
Vpo=430 V, E1/2=12 lux.sec.
Examples 132 through 140
Varieties of photosensitive materials having a structure illustrated in FIG. 2 were prepared by applying the same procedure as in Example 131 save for employing the respective disazo compounds referred to by number in the following Table-14 in place of the disazo compound No. 1C used in Example 131. When these photosensitive materials were subsequently subjected to the same measurement of Vpo and E1/2 as in Example 121, the result was as shown in Table-14, respectively.
TABLE 14______________________________________ DisazoExample compound Vpo E1/2No. No. (volt) (lux . sec.)______________________________________132 3C 450 12133 5C 480 13134 12C 490 12135 25C 520 15136 27C 450 10137 48C 440 11138 69C 450 10139 71C 440 10140 110C 440 20______________________________________
Example 141
10 parts by weight of polyester resin (the same as that in Example 121), 10 parts by weight of 2,5-bis(4-diethylaminophenyl)-1,3,4-oxadiazole, 2 parts by weight of the disazo compound No. 1C and 198 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was dried at a temperature of 120° C. for 10 minutes, whereby there was prepared a photosensitive material having a 10μ-thick photosensitive layer and a structure illustrated in FIG. 2. When this photosensitive material was subsequently subjected to the same measurement as in Example 121, the result was as follows:
Vpo=820 V, E1/2=8 lux.sec.
Examples 142 through 150
Varieties of photosensitive materials having a structure illustrated in FIG. 2 were prepared by applying the same procedure as in Example 141 save for employing the respective disazo compounds referred to by number in the following Table-15 in place of the disazo compound No. 1C used in Example 141. When these photosensitive materials were subsequently subjected to the same measurement of Vpo and E1/2 as in Example 121, the result was as shown in the following Table-15, respectively.
TABLE 15______________________________________ DisazoExample compound Vpo E 1/2No. No. (volt) (lux. sec.)______________________________________142 17C 800 5143 27C 800 9144 56C 790 35145 62C 800 30146 67C 820 10147 71C 820 10148 83C 800 8149 101C 810 10150 126C 830 20______________________________________
Example 151
200 parts by weight of poly-N-vinyl carbazole, 33 parts by weight of 2,4,7-trinitro-9-fluorenone, 20 parts by weight of polyester resin (the same as that in Example 121) and 20 parts by weight of the disazo compound No. 1C as added to 1780 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was dried at a temperature of 100° C. for 10 minutes and at a temperature of 120° C. for 5 minutes in succession, whereby there was obtained a photosensitive material having a 13μ-thick photosensitive layer and a structure illustrated in FIG. 2. When this photosensitive material was subjected to the same measurement as in Example 121, the result was as follows:
Vpo=1,000 V, E1/2=5 lux.sec.
Examples 152 through 160
Varieties of photosensitive materials having a structure illustrated in FIG. 2 were prepared by applying the same procedure as in Example 151 save for employing the respective disazo compound referred to by number in the following Table-16 in place of the disazo compound No. 1C used in Example 151. When these photosensitive materials were subsequently subjected to the same measurement of Vpo and E1/2 as in Example 121, the result was as shown in the following Table-16, respectively.
TABLE 16______________________________________ DisazoExample compound Vpo E 1/2No. No. (volt) (lux. sec.)______________________________________152 3C 1100 5153 5C 1100 3154 19C 1000 8155 55C 900 15156 67C 980 5157 91C 1020 3158 110C 1040 8159 123C 1080 18160 127C 1200 25______________________________________
Example 161
2 parts by weight of the disazo compound No. 1C and 98 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was subjected to natural drying, whereby there was formed a 1μ-thick charge-carrier generating layer. Meanwhile, another dispersion was prepared by mixing 2 parts by weight of 2,4,7-trinitro-9-fluorenone, 2 parts by weight of polycarbonate (namely, Panlite L, the manufacture of TEIJIN Co., Ltd.) and 46 parts by weight of tetrahydrofuran together, and this dispersion was coated on the foregoing charge-carrier generating layer by means of a doctor blade and then dried at a temperature of 100° C. for 10 minutes to form a 10μ-thick charge-transfer medium layer, whereby there was obtained a photosensitive material having a structure illustrated in FIG. 3. When the thus obtained photosensitive material was subjected to the same measurement as in Example 121, the result was as follows:
Vpo=920 V, E1/2=15 lux.sec.
Examples 162 through 170
Varieties of photosensitive materials having a structure illustrated in FIG. 3 were prepared by applying the same procedure as in Example 161 save for employing the respective disazo compounds referred to by number in the following Table-17 in place of the disazo compound No. 1C used in Example 161. When these photosensitive materials were subjected to the same measurement of Vpo and E1/2 as in Example 121, the result was as shown in Table-17, respectively.
TABLE 17______________________________________ DisazoExample compound Vpo E 1/2No. No. (volt) (lux. sec.)______________________________________162 3C 980 15163 5C 920 12164 19C 900 10165 55C 950 20166 67C 930 10167 91C 990 8168 110C 990 10169 123C 920 19170 127C 1000 30______________________________________
Example 171
2 parts by weight of the disazo compound 1C and 98 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was subjected to natural drying, whereby there was formed a 1μ-thick charge-carrier generating layer. Meanwhile, another dispersion was prepared by mixing 2 parts by weight of 2,5-bis(4-diethylaminophenyl)-1,3,4-oxadiazole, 2 parts by weight of polycarbonate (the same as that in Example 151) and 46 parts by weight of tetrahydrofuran together, and this dispersion was coated on the foregoing charge-carrier generating layer by means of a doctor blade and then dried at a temperature of 120° C. for 10 minutes to form a 10μ-thick charge-transfer medium layer, whereby there was obtained a laminate-type photosensitive material illustrated in FIG. 3. When the thus obtained photosensitive material was subjected to the same measurement of Vpo and E1/2 as in Example 121 save for applying -6 KV corona discharge instead of +6 KV corona discharge, the result was as follows:
Vpo=990 V, E1/2=8 lux.sec.
Examples 172 through 180
Varieties of photosensitive materials having the same structure as that of Example 171 were prepared by employing the respective disazo compound referred to by number in the following Table-18 in place of the disazo compound No. 1C used in Example 171. When these photosensitive materials were subjected to the same measurement of Vpo and E1/2 as in Example 121, the result was as shown in Table-18, respectively.
TABLE 18______________________________________ DisazoExample compound Vpo E 1/2No. No. (volt) (lux. sec.)______________________________________172 3C 900 10173 5C 890 10174 19C 910 12175 55C 910 25176 67C 900 12177 91C 880 18178 110C 870 15179 123C 890 20180 127C 900 35______________________________________
Example 181
1 parts by weight of polyester resin (namely, Polyester Adhesive 49000, the manufacture of Du Pont Inc.), 1 part by weight of the disazo compound 1D and 26 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was dried at a temperature of 100° C. for 10 minutes, whereby there was obtained a photosensitive material having a 7μ-thick photosensitive layer and a structure illustrated in FIG. 1.
Subsequently, after charging positive electricity on the photosensitive layer of this photosensitive materials by applying +6 KV corona discharge for 20 seconds by means of a commercial electrostatic copying paper testing apparatus, the photosensitive material was left alone in the dark for 20 seconds, and the surface potential Vpo(volt) at that time was measured. Next, light was applied to the photosensitive layer by means of a tungsten lamp so as to attain the illumination of 20 luxes on the surface thereof, and the time (unit: second) required for reducing said surface potential Vpo to half was sought, whereby the amount of exposure E1/2 (lux.sec.) was obtained. The result was as follows:
Vpo=500 V, E1/2=15 lux.sec.
Examples 182 through 190
Varieties of photosensitive materials were prepared by applying the same procedure as in Example 181 save for employing the respective disazo compounds referred to by number in the following Table-19 in place of the disazo compound No. 1D used in Example 181. When these photosensitive materials were subsequently subjected to the same measurement of Vpo and E1/2 as in Example 181, the result was as shown in Table-19, respectively.
TABLE 19______________________________________ DisazoExample compound Vpo E 1/2No. No. (volt) (lux. sec.)______________________________________182 4D 620 10183 17D 620 10184 18D 700 12185 32D 710 14186 37D 700 25187 49D 690 30188 58D 690 30189 62D 700 20190 65D 800 35______________________________________
Example 191
10 parts by weight of polyester resin (the same as that in Example 181), 10 parts of weight of 2,4,7-trinitro-9-fluorenone, 2 parts by weight of disazo compound No. 1D and 198 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was dried at a temperature of 100° C. for 10 minutes, whereby there was obtained a photosenitive material having a 10μ-thick photosensitive layer and a structure illustrated in FIG. 2. Subsequently, measurement of Vpo and E1/2 of this photosensitive material was conducted through the same procedure as in Example 181 save for applying -6 KV corona discharge instead of +6 KV corona discharge employed in Example 15. The result was as follows:
Vpo=500 V, E1/2=8 lux.sec.
Examples 192 through 200
Varieties of photosensitive materials having a structure illustrated in FIG. 2 were prepared by applying the same procedure as in Example 191 save for employing the respective disazo compounds referred to by number in the following Table-20 in place of the disazo compound No. 1D used in Example 181. When these photosensitive materials were subsequently subjected to the same measurement of Vpo and E1/2 as in Example 181, the result was as shown in Table-20, respectively.
TABLE 20______________________________________ DisazoExample compound Vpo E 1/2No. No. (volt) (lux. sec.)______________________________________192 3D 490 8193 5D 480 5194 11D 500 9195 23D 500 15196 25D 480 18197 35D 520 20198 38D 500 20199 41D 490 18200 60D 630 18______________________________________
Example 201
10 parts by weight of polyester resin (the same as that in Example 181), 10 parts by weight of 2,5-bis(4-diethylaminophenyl)-1,3,4-oxadiazole, 2 parts by weight of the disazo compound No. 1D and 198 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was dried at a temperature of 120° C. for 10 minutes, whereby there was prepared a photosensitive material having a 10μ-thick photosensitive layer and a structure illustrated in FIG. 2. When this photosensitive material was subsequently subjected to the same measurement as in Example 181, the result was as follows:
Vpo=800 V, E1/2=6 lux.sec.
Examples 202 through 210
Varieties of photosensitive materials having a structure illustrated in FIG. 2 were prepared by applying the same procedure as in Example 201 save for employing the respective disazo compounds referred to by number in the following Table-21 in place of the disazo compound No. 1D used in Example 201. When these photosensitive materials were subsequently subjected to the same measurement of Vpo and E1/2 as in Example 181, the result was as shown in the following Table-21, respectively.
TABLE 21______________________________________ DisazoExample compound Vpo E1/2No. No. (volt) (lux . sec.)______________________________________202 2D 950 10203 9D 900 12204 13D 920 8205 28D 930 15206 33D 890 16207 45D 900 19208 47D 900 20209 52D 890 21210 66D 950 25______________________________________
Example 211
200 parts by weight of poly-N-vinyl carbazole, 33 parts by weight of 2,4,7-trinitro-9-fluorenone, 20 parts by weight of polyester resin (the same as that in Example 181) and 20 parts by weight of the disazo compound No. 1D as added to 1780 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was dried at a temperature of 100° C. for 10 minutes and at a temperature of 120° C. for 5 minutes in succession, whereby there was obtained a photosensitive material having a 13μ-thick photosensitive layer and a structure illustrated in FIG. 2. When this photosensitive material was subjected to the same measurement as in Example 181, the result was as follows:
Vpo=1,000 V, E1/2=3 lux.sec.
Examples 212 through 220
Varieties of photosensitive materials having a structure illustrated in FIG. 2 were prepared by applying the same procedure as in Example 211 save for employing the respective disazo compounds referred to by number in the following Table-22 in place of the disazo compound No. 1D used in Example 211. When these photosensitive materials were subsequently subjected to the same measurement of Vpo and E1/2 as in Example 181, the result was as shown in the following Table-22, respectively.
TABLE-22______________________________________ SisazoExample compound Vpo E1/2No. No. (volt) (lux.sec.)______________________________________212 9D 1020 5213 10D 1000 3214 17D 1120 8215 29D 1000 6216 40D 995 10217 42D 1150 8218 51D 1200 12219 63D 1200 15220 64D 1210 15______________________________________
Example 221
2 parts by weight of the disazo compound No. 1D and 98 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was subjected to natural drying, whereby there was formed a 1μ-thick charge-carrier generating layer. Meanwhile, another dispersion was prepared by mixing 2 parts by weight of 2,4,7-trinitro-9-fluorenone, 2 parts by weight of polycarbonate (namely, Panlite L, the manufacture of TEIJIN Co. Ltd.) and 46 parts by weight of tetrahydrofuran together, and this dispersion was coated on the foregoing charge-carrier generating layer by means of a doctor blade and then dried at a temperature of 100° C. for 10 minutes to form a 10μ-thick charge-transfer medium layer, whereby there was obtained a photosensitive material having a structure illustrated in FIG. 3. When the thus obtained photosensitive material was subjected to the same measurement as in Example 181, the result was as follows:
Vpo=800 V, E1/2=15 lux.sec.
Examples 222 through 230
Varieties of photosensitive materials having a structure illustrated in FIG. 3 were prepared by applying the same procedure as in Example 221 save for employing the respective disazo compounds referred to by number in the following Table-23 in place of the disazo compound No. 1D used in Example 221. When these photosensitive materials were subjected to the same measurement of Vpo and E1/2 as in Example 181, the result was as shown in Table-23, respectively.
TABLE-23______________________________________ DisazoExample compound Vpo El/2No. No. (volt) (lux . sec.)______________________________________222 8D 850 9223 15D 800 10224 21D 870 8225 30D 880 15226 33D 890 20227 43D 900 10228 53D 865 10229 55D 880 18230 61D 900 25______________________________________
Example 231
2 parts by weight of the disazo compound No. 1D and 98 parts by weight of tetrahydrofuran were pulverized and mixed together within a ball-mill, and the resulting dispersion was coated, by means of a doctor blade, on a polyester film deposited with aluminum through vacuum evaporation and was subjected to natural drying, whereby there was formed a 1μ-thick charge-carrier generating layer. Meanwhile, another dispersion was prepared by mixing 2 parts by weight of 2,5-bis(4-diethylaminophenyl)-1,3,4-oxadiazole, 2 parts by weight of polycarbonate (the same as that in Example 221) and 46 parts by weight of tetrahydrofuran together, and this dispersion was coated on the foregoing charge-carrier generating layer by means of a doctor blade and then dried at a temperature of 120° C. for 10 minutes to form a 10μ-thick charge-transfer medium layer, whereby there was obtained a laminate-type photosensitive material illustrated in FIG. 3. When the thus obtained photosensitive material was subjected to the same measurement of Vpo and E1/2 as in Example 181 save for applying -6 KV corona discharge instead of +6 KV corona discharge, the result was as follows:
Vpo=1,000 V, E1/2=8 lux.sec.
Examples 232 through 240
Varieties of photosensitive materials having the same structure as that of Example 231 were prepared by employing the respective disazo compound referred to by number in the following Table-24 in place of the disazo compound No. 1D used in Example 231. When these photosensitive materials were subjected to the same measurement of Vpo and E1/2 as in Example 181, the result was as shown in Table-24, respectively.
TABLE-24______________________________________ DisazoExample compound Vpo El/2No. No. (volt) (lux . sec.)______________________________________232 6D 1000 8233 14D 990 8234 19D 980 10235 22D 990 8236 27D 1000 10237 36D 990 15238 44D 1000 8239 48D 1020 19240 53D 1100 25______________________________________ | The present invention provides electrophotographic sensitive materials having a high sensitivity as well as a high flexibility which comprise a conductive support and a photosensitive layer formed thereon, said photosensitive layer containing one disazo pigment, as an effective ingredient, which is selected from the group consisting of disazo pigments expressed by the following general formulas I, II, III, and IV, ##STR1## [(wherein A is selected from the group consisting of ##STR2## is selected from the group consisting of aromatic rings such as benzene ring, naphthalene ring, etc., hetero rings such as indole ring, carbazole ring, benzofuran ring, etc. and their substituents, Ar 1 is selected from the group consisting of aromatic rings such as benzene ring, naphthalene ring, etc., hetero rings such as dibenzofuran, etc. and their substituents, Ar 2 and Ar 3 are selected from the group consisting of aromatic rings such as benzene ring, naphthalene ring, etc. and their substituents, R 1 and R 3 are selected from the group consisting of hydrogen, lower alkyl radical or phenyl radical and their substituents and R 2 is selected from the group consisting of lower alkyl radical, carboxyl radical and their esters)]. | 2 |
CROSS-REFERENCE TO RELATED APPLICATION
[0001] The present application claims benefit from Chinese utility model application no. 201120410661.3 filed on Oct. 25, 2011 by Midea Group Co., Ltd. The entire disclosure of the application is hereby incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to a slow cooker and, in particular, to a portable slow cooker having a multi-functional handle and capable of preventing spillage of cooking content such as soup.
BACKGROUND OF THE INVENTION
[0003] Conventional slow cooker comprises a liner container and a lid disposed on the top rim of the container. The lid is typically not securely engaged with the container. The user is likely to move the cooker or the liner container containing food after the food is well cooked. The lid tends to slide off during movement because there is no secure connection between the liner container and the lid. Furthermore, the shaking caused by the movement can possibly cause spillage of the liquid content in the container, and thus may burn the user.
[0004] Chinese patent no. CN 200920198406.X discloses a slow cooker having a touch control panel, which comprises a working pot covered by a lid. A handle comprised of an upper part and a lower part is symmetrically fixed near the top edge of working pot. A spring hole is arranged in the middle of the lower part for accommodating a spring and a steel bead. A latch is slidably arranged between the upper and lower parts, and the movement of the latch is limited by the steel bead. A closed sealing ring, made of silicon gel, is arranged below the periphery of the lid to achieve seal connection between the lid and the working pot. The latch provided between the working pot and the lid is used to seal the working pot. However, this design has too many parts, resulting in high cost and difficulty of assembly. Moreover, the latch is subject to large area of friction, causing non-smooth operation. Further, the steel bead is positioned by the elastic force of the spring which may deteriorate during long term use, resulting in high possibility of latch release.
[0005] Chinese patent no. CN 200710005602 discloses a slow cooker comp g a housing, a container and a lid. The lid includes a gasket around an outer edge thereof and is shaped and sized to cover the opening of the container. At least one over-the-center clip is mounted to the side all of the housing, the clip being selectively engageable with the lid to retain the lid in sealing engagement with the container, in order to inhibit leakage of the food stuffs from the interior of the container. The clip includes a hook and a lever, the hook being selectively engageable with the lid to selectively retain the lid in sealing engagement with the container. A catch has to be provided to the lid in order to engage the hook of the clip. This will lead to additional cost and more complicated manufacturing process for mounting such a catch, particularly on a glass lid as predominately used in slow cookers.
[0006] Additionally, typical slow cooker available on the market, including the slow cookers disclosed in the above patents, are provided with ear-like grips on the two side walls of the housing for moving the slow cooker. Slow cooker with this structure requires to be operated with two hands simultaneously, and is not able to be moved with a single hand.
SUMMARY OUT THE INVENTION
[0007] The objective of the present invention is to provide a portable slow cooker capable of engaging a lid and a liner container to inhibit leakage of soup.
[0008] The second objective of the present invention is to provide a slow cooker that can be moved with a single hand.
[0009] The third objective of the present invention is to provide a slow cooker with a multi-functional handle.
[0010] The fourth objective of the present invention is to provide a slow cooker having a handle capable of engage a lid and a liner container.
[0011] To achieve the above objective, the below technical solution is adopted in the present invention.
[0012] A portable slow cooker, including a cooking body, a liner container, a lid and a handle, is provided in the present invention, wherein the liner container is disposed within the cooking body, and the lid is disposed on the opening of the liner container. The handle is spaned over the lid and has, lower ends in vertically slidable cooperation with handle boxed disposed at a side surface of the cooking body. The handle is locked by the handle boxes when slides to an, so as to press the said lid to form a scaling engagement with the liner container. When using the product of the present invention, the lid and the liner container can be locked by pushing and locking the handle to the lowest position, preventing the soup form spilling out. When the handle is pulled to the highest position, the slow cooker can be easily moved by hand. By delicate designing, the lock device of the lid and the handle are integrated together, simplifying the structures and bringing convenience for users. The lid is locked by the handle in the present invention. Therefore, no further manufacturing is needed for the lid. This is much more easily to manufacture with existing glass lids.
[0013] For easy opening of the lid or moving out of the liner container, the handle is rotatable with respect to the handle boxes when it is moved to the highest position by sliding. Therefore, when the handle is pulled to the highest position, it is able to rotate to one side, leaving no disturbance above the lid, making it easy to open the lid and remove the liner container.
[0014] To prevent the handle from sliding down to the lowest position to be locked under the gravity force, a restoring mechanism for supporting the handle is provided within the handle box. When the handle is unlocked at the lowest position, it can automatically leave the lowest position, with no need of manual operation, thus it is more easily to operate.
[0015] For easy movement with a single hand, the said handle has an inverted U shape, with two lower ends inserted into the handle boxes, to slide upward and downward. The crossbar of the handle is pressed against the lid when the handle is placed at the lowest position. The inverted-U shaped handle is not only convenient for movement with a single hand, but also connected to the two sides of the cooking body, and therefore is uniformly forced to move smoothly to prevent the soup from spilling out.
[0016] Typically the lid of the slow cooker is provided with a grip, and preferably, the crossbar of the handle is pressed against the grip of the lid when the handle is at the lowest position. In this way, the grip is pressed by the crossbar, with no direct connection to the lid, so that heat will rarely be transferred to the handle during cooking to prevent high temperature of the handle, and thus is convenient for users.
[0017] The handle can be locked at the lowest position via various ways. Two types of structure are provided in the present invention. The first type provides a handle with a lock catch at each of the lower ends, and each of the handle boxes is provided with a flexible pressing buckle, which is match with the said lack catch to lock the handle at the lowest position. Specifically, the said handle box includes a box base, a box lid, a positioning buckle and a trigger, wherein the restoring mechanism is a spring installed within the handle box, which is disposed on the box base. The trigger is rotatably connected to the box lid, and the positioning buckle is rotatably connected to the trigger. A slider that slides within the box base is rotatably connected to the lower end of the handle. This kind of structure is simplified and convenient for users, with strengthened locking force.
[0018] Another type provides a handle box with a two-stage positioning mechanism, in correspondence with the highest position and lowest position of the handle respectively. Specifically, each of the handle box includes a box base, a box lid, a positioning buckle, a resetting spring sheet and a trigger. The positioning buckle, the resetting spring sheet and the trigger are installed between the box lid and the box base. The restoring mechanism is a spring installed within the handle box. At one side of the positioning buckle is provided with a two-stage latching position, i.e., a higher one and a lower one. At the other side of the positioning buckle is provided with the resetting spring sheet supporting the positioning buckle. The positioning buckle is pushed by the trigger to press against the resetting spring sheet. A projecting rotate shaft, of which the end is provided with a position-limiting projection, is provided to the lower end of the handle to match with the two stage latching positions. For this kind of structure, the locking force is strengthened. It can be unlocked by pushing the trigger, and thus is convenient for users. Besides, no metal components as what is used in the previous type are required, therefore the temperature during operation can be lowered and make it more safe to operate.
[0019] In a word, the handle and the locking device of the lid are delicately integrated as a whole, with simplified structure and strengthened locking force to prevent the soup from spilling out during operation. It is convenient to remove the lid and the liner container and move with a single hand. It requires no further manufacture of the locking component on the lid, and thus is more easily to manufacture, suitable for lid made of any kind of materials, e.g., glass or ceramics. The locking mechanism and the unlocking mechanism are both disposed on the cooking body of the slow cooker, with little heat transferring, protecting the users from being burned during operation, owning to the high efficiency in decreasing the temperatures of these mechanisms. Compared with the prior arts, it is creative with substantive characteristics and obvious progress.
BRIEF DESCRIPTION OF THE DRAWINGS
[0020] FIG. 1 is a structural installation diagram of the first embodiment;
[0021] FIG. 2 is a structural exploded view of the first embodiment;
[0022] FIG. 3 is an enlarged view of A in FIG. 1 ;
[0023] FIG. 4 is a side view of the first embodiment, wherein the lid is unlocked and the handle is displayed vertically;
[0024] FIG. 5 is a cutaway view of the first embodiment, wherein the lid is unlocked and the handle is displayed vertically;
[0025] FIG. 6 is a schematic diagram of the handle box, wherein the lid is unlocked and the handle is displayed vertically;
[0026] FIG. 7 is a side view of the first embodiment, wherein the lid is unlocked and the handle is tilted;
[0027] FIG. 8 is a cutaway view of the first embodiment in the transient state;
[0028] FIG. 9 is a schematic diagram of the handle box in the transient state;
[0029] FIG. 10 is a cutaway view of the first embodiment in the locked state;
[0030] FIG. 11 is a schematic diagram of the handle box in the locked state;
[0031] FIG. 12 is a structural exploded view of the handle box of the first embodiment;
[0032] FIG. 13 is a structural exploded view in another angle of the handle box of the first embodiment;
[0033] FIG. 14 is a transforming structural diagram of the handle box of the first embodiment;
[0034] FIG. 15 is a structural installation diagram of the second embodiment;
[0035] FIG. 16 is a structure exploded view of the second embodiment;
[0036] FIG. 17 is a schematic diagram of the second embodiment, wherein the lid is unlocked and the handle is displayed vertically;
[0037] FIG. 18 is a cutaway view of the second embodiment, wherein the lid is unlocked and the handle is displayed vertically;
[0038] FIG. 19 is a side view of the second embodiment, wherein the lid is unlocked and the handle is leaning;
[0039] FIG. 20 is a cutaway view of the second embodiment in the transient state;
[0040] FIG. 21 is a schematic diagram of the second embodiment in the locked state;
[0041] FIG. 22 is a cutaway view of the second embodiment in the locked state;
[0042] FIG. 23 is a structure exploded view of the handle box of the second embodiment;
[0043] FIG. 24 is a structure exploded view in another angle of the handle box of the second embodiment.
DETAILED DESCRIPTION OF THE EMBODIMENTS
[0044] The present invention is explained in further detail as below with reference to the drawings.
Embodiment 1
[0045] The portable slow cooker in this embodiment as show in FIGS. 1 to 14 includes a cooking body 3 , a liner container 2 disposed within the cooking body 3 , a lid 1 disposed on the liner container 2 covering the opening end of the liner container 2 , a handle 4 , a handle box 5 fixed on the two end side surface of the cooking body 3 , and a sealing ring 6 disposed around the outer rim of the lid 1 , and Within the handle box 5 is provided with a handling position and a fixed position. The handle 4 has two lower ends that can remove upward and downward to be fixed in the handle box 5 , and selectively be fixed at the handling position or fixed position of the handle box 5 , has an inverted U shape, and is disposed over the lid 1 . When the two ends of the handle 4 are fixed at the fixed position of the handle box 5 , the handle press tightly on the grip of the lid 1 , making the lid 1 , the sealing ring 6 and the liner container 2 closely joint together, insuring food within the liner container not spill out or pour out. When the two ends of the handle 4 are at the handle position of the handle box 5 , the pressing force upon the lid 1 by the handle 4 is released, so that the lid 1 and the liner container 2 can be picked up or placed freely, and the handle 4 can also rotate freely.
[0046] As shown in FIGS. 2 and 12 , the handle box 5 of the present embodiment comprises a box base 51 , a box lid 52 , a positioning buckle 53 , a resetting spring sheet 54 and a trigger 55 . The box base 51 was fixed to the cooking body 3 via fasteners, e.g., screws. The outside wall of the box base 51 is closely next to the side wall of the cooking body 3 . The inner side wall of the box base is provided with a horizontally projecting spindle 511 and 512 . The box lid 52 is fixed on the box base 51 via fasteners, e.g., screws, and a cavity is formed between the box lid 52 and the box base 51 . Along the vertical direction of the outsider of the box lid 52 is provided with a locating cylinder 522 , which has an upper end opened, for the upward and downward movement of the handle. A slide groove 521 is disposed on the box lid 52 , corresponding to the locating cylinder 522 , and the box lid 52 is provided with a hole 523 in the lower end.
[0047] The positioning buckle 53 of sheeting structure is provided with a axial-hole 531 and a fillister shaped higher latching position 532 in the upper end, and with a fillister shaped lower latching position in the lower end, wherein a cam shaped or inclined face transition is formed between the bottom of the higher latching position 532 and the top of lower latching position 533 . The higher latching position 532 is the handling position of the handle box, and the lower latching position 533 is the fixed position of the handle box. Via the matching of the axial-hole 531 and the spindle 511 , the positioning buckle 53 is assembled within the chamber between the box base 51 and the box lid 52 .
[0048] The arc shaped resetting spring sheet 54 , engaged at the side of the positioning buckle 53 , has a hook 541 in the end which is matched with the edge 512 to fix the resetting spring sheet 54 within the chamber between the box base 51 and the box lid 52 , The spring force formed by the resetting spring sheet 54 against the positioning buckle 53 enable the positioning buckle 53 to rotate around the spindle 511 in a certain angle.
[0049] The trigger 55 is utilized by users to overcome the spring force of the resetting spring sheet 54 , enable the positioning buckle 53 to rotate in the reverse direction to relieve the locked status, to switch the handle 4 from the fixed position of the handle box 5 to the handle position. The trigger 55 and the positioning buckle 53 are integrally designed in the present embodiment. The trigger 55 , horizontally projecting through the hole 523 in the lower end of the box lid 55 , is positioned at the bottom of the positioning buckle 53 . To obtain a similar effect, the trigger 55 may also be dependent from the positioning buckled, and then fixedly assembled together.
[0050] To increase the upward restoring force of the handle from the fixed position to the handle position, a spring 56 , which has one end abutting on the end of the handle 4 , and another end abutting on the bottom of the locating cylinder 522 of the box lid, can be further provided in the present embodiment.
[0051] Referring to FIG. 10 , each of the ends of the handle 4 is provided with a projecting rotate shaft 41 in the horizontal direction and a groove 43 in the vertical direction, in the present embodiment. A position-limiting projection 42 of a rather big size is provided at the end of the rotate shaft 41 , to prevent the handle from sliding off the handle box. The groove 43 is use for engaging the spring 56 , to locate the telescopic position of the spring 56 .
[0052] Moving mechanism of the present embodiment is as follows:
[0053] As shown in FIGS. 4 , 5 , 6 , and 7 , each of the ends of the handle is positioned at the opening of the locating cylinder 522 . The position-limiting projection 42 of the handle goes through the slide groove 521 and the higher latching position 532 of the positioning buckle, to engage the rotate shaft 41 in the slide groove 521 and the higher latching position 532 of the positioning buckle in this circumstance, the positioning buckle 53 , the resetting spring sheet 54 and the spring 56 are on the status of free resetting, where the handle 4 is fixed at the handle position of the handle box 5 , not stressed, and may rotate around the rotate shaft 41 , having not locked the lid 1 and the liner container 2 . When the handle 4 rotates to a vertical direction as shown in FIG. 4 , the rotate shaft 41 of the handle is engaged at the top of the slide groove 521 , and the position-limiting projection 42 is engaged at the top of the higher latching position 532 of the positioning buckle, and therefore the handle is fixed within the handle box out any possibility of sliding off, and the slow cooker can be lifted by lifting the handle upward to move in a short distance. While the handle 4 rotates to an inclined direction as shown in FIG. 7 , the liner container 2 and the lid 1 can be conveniently picked and placed.
[0054] As shown in FIGS. 1 and 9 when the handle is positioned in the vertical direction, unlocked, the handle 4 will overcome the force of the spring 56 to move along the locating cylinder 522 if a stress is forced on the handle 4 downward, then the rotate shaft 41 of the handle will move downward along the slide groove 521 , and press the cam shaped junction between the higher latching position 532 and the lower latching position 532 , making the positioning buckle press the resetting spring sheet 54 and rotate around the spindle 511 , until the rotate shaft 41 move to the lower latching position 533 of the positioning buckle. As shown in FIGS. 10 and 11 . The positioning buckle 53 rotates reversely under the reacting force of the resetting spring sheet 54 , engaging the rotate shaft 41 at the lower latching position 533 , and thus the handle 4 is fixed at the fixed position of the handle box. The handle 4 press tightly on the grip of the lid 1 , forming a tight fitness among the lid 1 , the sealing ring 6 and the liner container 2 , in this locked status, food within the liner container will not spill out or pour out, and thus the whole slow cooker can be lifted, or be suitable for long distance movement, or be placed on cars or other carriers that may slightly jounce.
[0055] When the slow cooker is under locked status as shown in FIG. 10 , the positioning buckle 53 can be driven to press the resetting spring sheet 54 and rotate around the spindle 511 by applying a horizontal force on the trigger 55 . The rotate shaft 41 of the handle leave the lower latching position 533 , and simultaneously, under the upward force by the users or the restoring force by the spring 56 , the handle 4 drives the rotate shaft 41 to move upward along the locating cylinder 522 , engaging the rotate shaft 41 at the higher latching position 532 , and therefore, it returns to a free status, unlocked, as shown in FIG. 4 , where the handle 4 can return from the fixed position of the handle box to the handle position.
[0056] As shown in FIG. 14 , the spring 56 in the present embodiment is substituted by a tension spring 56 ′. The tension spring 56 ′, which has one end fixed on the box base, and another end fixed on the rotate shaft 41 of the handle, can be equally effective.
[0057] The resetting spring sheet 54 can be substituted by a compression spring in the present embodiment. The compression spring, which has one end abutting on the side wall of the box base, and another end abutting on the side wall of the positioning buckle, can be equally effective.
[0058] In the locked status of the present embodiment, the handle box 4 presses tightly on the grip of the lid 1 , forming a tight fitness among the lid 1 , the scaling ring 6 and the liner container 2 . Of course, if the structure of the handle 4 is improved, it will still be within the protection scope of the present invention, e.g., the width of the handle 4 corresponding to the grip of the lid is broadened, and a hole is provided in the center, so that the handle 4 can avoid the grip of the lid 1 , press tightly on other elements of the lid 1 , forming a tight fitness among the lid 1 , the sealing ring 6 , and the liner container 2 .
Embodiment 2
[0059] As shown in FIGS. 15 to 24 , the slow cooker in the present embodiment includes a cooking body 3 ′, an liner container 2 ′ disposed within the cooking body 3 ′, an lid 1 ′ disposed on the liner container 2 ′ covering the opening of the liner container 2 ′, a handle 4 ′, a handle box 5 ′ fixed on the two end side surface of the cooking body 3 ′, and a sealing ring 6 ′ disposed around the outer rim of the lid 1 ′.
[0060] Different from the embodiment 1 , the handle box 5 ′ in the present embodiment includes a box base 51 ′, a box lid 52 ′, a positioning buckle 53 ′, a trigger 55 ′, and a spring 56 ″. The box base 51 ′ is fixed to the cooking body 3 ′ via fasteners, e.g., screws. The outside wall of the box base 51 ′ is closely next to the side wall of the cooking body 3 ′. The inner side wall of the box base 51 ′ is provided with two parallel locating wings 513 ′ in the vertical direction. A skid 514 ′ for the upward and downward movement of the handle 4 ′ is formed between the two locating wings 513 ′. A fillister 515 ′ is provided at the top end of the skid 514 ′, forming the handle position of the handle box 5 ′ at the area of the fillister 515 ′. The fix position of the handle box 5 ′ is formed at the lower end of the skid 514 ′.
[0061] The box lid 52 ′ is fixed on the box base 51 ′ via fasteners, e.g., screws, and a cavity is formed between the box lid 52 ′ and the box base 51 ′. The upper part of the box lid 52 ′ corresponding to the skid 514 ′ of the box base is provided with a groove 524 ′ for the assembly and movement of the handle 4 ′. Each of the two side walls of the groove 524 ′ is provided with a horizontal extrusion facing toward the box base 51 ′ at the top, and with a parallel barrier walls 525 ′ in the vertical direction at the middle part, wherein the barrier walls 525 ′ is provided with horizontally projecting assembling shafts 526 ′, respectively, facing each other. The positioning buckle 53 ′ of which the top end forms a latching position 534 ′, and the lower end is provided with a snap-in hook 535 ′, has an inverted U shape.
[0062] The upper end of the trigger 55 ′ of the present embodiment is provided with two legs, each of which is provided with a sleeve 551 ′ at the end, respectively. The size of the sleeve 551 ′ is in correspondence with the assembling shaft 526 ′ of the box lid, and by matching with the assembling shaft 526 ′, the trigger 55 ′ are driven to rotate around the assembling shaft 526 ′. At the middle part of the legs are provided with a support shaft 552 ′ which forms a connection between the two legs. The size of the support shaft 552 ′ is in correspondence with the snap-in hook 535 ′ of the positioning buckle, and via the matching of the support shaft 552 ′ and the snap-in hook 535 ′, the positioning buckle 53 ′ is rotatably fixed to the support shaft 552 ′, forming a hinge structure with the trigger 55 ′.
[0063] To enhance the upward restoring force of the handle 4 ′, a spring 56 ″, which has one end abutting on the end of the handle 4 , and another end abutting on the bottom of the handle box 5 ′, is further provided in the present embodiment.
[0064] Each of the two ends of the handle 4 ′ is provided with an outward projecting lock catch 44 ′ When the trigger 55 ′ rotate around the assembling shaft 526 ′, the lock catch 44 ′ can be engaged into the latching position 534 ′ of the positioning buckle 53 ′, enforcing the handle 4 ′. Slider 45 ′ is respectively movably fixed to each of the ends of the handle box 4 ′, via connecting elements 46 ′, which has end designed as spherical surface to match with the fillister 515 ′ of the skid. The slider 45 ′ has an inverted T shape, defined within the skid 541 ′ by the two side walls of the groove 524 ′, the horizontal extrusion of the side wall and the barrier wall 525 ′.
[0065] Moving mechanism of the present embodiment is as follows:
[0066] As shown in FIGS. 17 and 18 , the slider 45 ′ of the handle is disposed at the upper end of the skid 514 ′, the spherical surface of the connecting element 46 ′ is matched with the fillister 515 ′ of the skid 514 ′. In this status, the handle 4 ′ is fixed in the handle position of the handle box 5 ′. The positioning buckle 53 ′, the trigger 55 ′ and the spring 56 ″ are on the status of free resetting, and the handle 4 ′ are unstressed, having not locked the lid 1 ′ and the liner container 2 ′, and may rotate around the connecting element 46 ′. When the handle 4 ′ rotates to the vertical direction as shown in FIG. 17 , the slider 45 ′ of the handle is located by the two side walls of the groove 524 ′ and the horizontal extrusion at the top of the two said side walls: The handle 4 ′ is restricted within the handle box 5 ′. Thus, the slow cooker can be lifted by lifting the handle 4 ′ upward, and is suitable for picking and placing properly in a short distance. When the handle 4 ′ rotates to an inclined direction as shown in FIG. 19 , the liner container 2 ′ and the lid 1 ′ can be conveniently picked and placed.
[0067] As shown in FIG. 20 , when the handle is in the vertical direction as shown in FIG. 17 , unlocked, the trigger 55 ′ will be driven to rotate upward around the assembling shaft 526 ′ if the trigger 55 ′ is forced, and thus the positioning buckle 53 ′ removes upward, rotatable around the trigger 552 ′. When the trigger 55 ′ and the positioning buckle 53 ′ rotate through the dot line from the free status to the solid line as shown in the figure, the lock catch 44 ′ can be engaged and interfered by the positioning buckle 53 ′, and thus, the force of the spring 56 ″ can be overcome by the handle 4 ′ by applying a reacting force on the trigger 55 ′, moving downward along the skid 514 ′, until the handle 4 ′ reaches the lower end of the skid 514 ′ of the handle box. As shown in FIGS. 21 and 22 . Because of the self-locking characters of the trigger 55 ′, it will not release by itself, and thus the handle 4 ′ is fixed at the fixed position of the handle box 5 ′, pressing tightly on the lid 1 ′, forming a tight fitness among the lid 1 ′, the sealing ring 6 ′ and the liner container 2 ′. Therefore, it is on the locked status, preventing the food within the liner container 2 ′ from spilling out or pouring out. In this case, the whole slow cooker can be lifted, suitable for long distance movement, or for placing on cars or other carriers that may slightly jounce.
[0068] When the slow cooker is on the locked status, as shown in FIG. 21 , the trigger can overcome the locking force of itself to rotate upward by applying a force on the trigger 55 ′. Thus the interference force on the handle by the positioning buckle 53 ′ is released, and the handle 4 ′ can make the slider 45 ′ to move upward along the skid 514 ′ of the box base, by the upward force applied by the users, or by the resetting force of the spring 56 ″. Then, the connecting element 46 ′ is matched with the fillister 516 ′ of the box base, and the handle 4 ′ returns to the higher latching position of the handle box 5 ′, returning to the free status as shown in FIG. 17 , unlocked, and therefore the handle 4 ′ returns from the fixed position of the handle box 5 ′ to the handle position. | A new portable slow cooker capable of engaging a lid and a liner container can is provided to prevent the soup from spilling out. The structure of the present invention comprises a cooking body, a liner container, a lid and a handle, wherein the liner container is disposed within the cooking body, and the lid is disposed on the opening of the liner container. The handle is spanned over the lid and has, lower ends in vertically slidable cooperation with handle boxes disposed at aside surface of the cooking body. The handle is locked by the handle boxes when slides to an lowest position, so as to press the lid to form a sealing engagement with the liner container. As long as the handle is pushed to the lowest position, being locked, the lid and the liner. container can be engaged to prevent the soup from spilling out. | 0 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to optical components in silicon oxide and/or other mixed metallic oxides having dimensional precision which has surface roughness tolerance and profilometric accuracy within the specifications described for visible and ultraviolet spectrum ranges.
The above manufactured articles have “final” or “almost final” dimensions as they are obtained by the isotropic dimensional reduction (miniaturization) of amorphous monolithic materials, called aerogels, in turn prepared by means of cold moulding techniques based on sol-gel processes.
The process for the preparation of the above objects involves the accurate geometrical definition of the aerogel by:
the cold filling of a suitable mould with a liquid colloidal dispersion, called sol, formed from specific chemical precursors;
the polycondensation of the sol to obtain the respective gels therefrom (gelation);
the supercritical drying of the gels until aerogels are obtained with dimensions corresponding to the mould used;
the isotropic reduction (miniaturization) of the amorphous monolithic aerogels thus obtained, consisting of silicon oxide alone or in the presence of one or more oxides of elements belonging to groups III to VI of the Periodical Table and exceptionally also other groups.
2. Description of the Background
It is known that optical materials, and in particular transparent optical materials such as silica or molten quartz and optical glass, owing to their hardness and fragility, are difficult to process as the direct hot moulding of these optical components and devices is generally not possible for reasons of product quality.
The traditional method for producing these optical elements is based on the reduction of an adequate preform to the end product by means of slow, precise grinding operations.
Whereas some of these operations, such as reduction with both a flat and spherical surface, can be automized, others, such as aspherical finishing, require complicated manual processes.
This operational difficulty results in a limited process flexibility on an industrial scale and unreasonably high costs to obtain quality products such as optical components and devices based on the above aspherical optical system.
Owing to these technological limitations the optical industry has tried to solve the problem in various ways.
One of these is the moulding at high pressure and temperature of aspherical lenses and other optical components, directly from appropriate preforms of the optical material desired; with this method, which requires extremely sophisticated equipment such as a hot hydrostatic press, high quality products are obtained but also at a high cost and the process consequently necessitates very substantial investments.
One way of reducing the costs is by the use of organic optical materials, in particular plastics.
These materials can be melted and moulded with much more economical processes and can also be very easily processed with machine tools.
Unfortunately the dimensional precision of the optical products obtained generally by melting, is negatively influenced both by the insufficiently controllable shrinking of the material during the cooling operation and by the change of liquid-solid phase which causes a dimensional distorsion and deterioration of the optical quality of the manufactured article.
Also with the use of mechanical processing with machine tools, the optical products obtained from plastic materials do not have an acceptable quality as the material cannot be accurately processes owing to the fact that it is too soft.
In addition, the products which can be obtained with the above plastic materials, by hot moulding or mechanical processing, suffer from limited chemical and dimensional stability and do not reach the durability standards established for inorganic optical materials.
It is also known that optical components with definite dimensions can be obtained by suitably treating a gel deriving from the hydrolysis of a silicon alkoxide.
For example, U.S. Pat. No. 4,680,049 describes a method for the preparation of optical glass based on silicon oxide which involves an initial hydrolysis of a silicon alkoxide, the drying of the above gel and a final thermal syntherization treatment until an optical glass with definite dimensions is obtained.
These “final” optical products however have a very significant deviation with respect to the profile of the aerogel, as is amply illustrated in FIG. 1 .
The two diagrams shown in the above figure represent the configuration of the upper surface of the aerogel (diagram A) and the corresponding surface of the densified product (diagram B) respectively.
In the mould in which the gel is prepared the corresponding surface is rigorously flat: it can be seen how the flat surface of the mould passes to a convex surface in the aerogel to end up as a concave surface in the densified product.
The distorsion of the manufactured article is herein quantified as follows: distorsion from mould to aerogel = 20 μm 3000 μm × 100 = 0.67 % distorsion from aerogel to glass = 40 μm 2000 μm × 100 = 2 %
This process, which herein is simply indicated as “compensated distorsion process”, is severely limited in its industrial applications as there are difficulties in programming specific geometries of the product.
In fact, as there is no biunivocal, continuous correspondence between the geometry of the mould and that of the product, there is also no rational control of the final dimensions of the product itself.
Another attempt at developing the processing technology of optical materials has been made using machine tools with a very high precision numerical control, having a diamond point so as to be also able to process hard materials such as quartz and optical glass and with movement on air bearings to minimize the vibrations of the tool point.
These machines have been successfully developed in the last ten years and reach precision in the profile control of about a tenth of a micrometer and, under favourable conditions, even higher precision in the control of the surface roughness; they are consequently capable of finishing an item with so-called “optical” precision, which means a precision which is suitable for optics limited within the infrared spectrum range.
On the other hand, the above machines are still not adequate for applications in visible and ultraviolet spectrum ranges owing to the more severe specifications of surface roughness and profilometric accuracy required by optical laws within these spectrum ranges.
In addition, this high precision processing, which although economically convenient in special applications such as mirror finishing by laser in copper, aluminium or other materials typically used in infrared, is not generally economical for obtaining transparent optical components based on silica or inorganic glass, for numerous reasons including the hardness and fragility of the materials.
It is known in fact that these machines can be well used in the processing of typical materials for applications in infrared; this is due to their processability characteristics which are much higher than optical glass.
This creates great difficulties in the spectrum ranges, where glass is the prevalent material for which the technology of the single rotating diamond point (S.P.T.D.M.) cannot be used because of its fragility.
As described in Italian patent application MI-92A02038 filed by the Applicant, these high precision machine tools are used on intermediates to obtain perfectly and completely isotropic optical components and devices in “final” or “almost final” dimensions; the above intermediates, as they have the property of isotropically shrinking, are monolithic aerogels ideally amorphous of silica and/or other metallic oxides produced according to the technolgy described in U.S. Pat. No. 5,297,814.
SUMMARY OF THE INVENTION
The Applicant has now found that gels prepared with the technology of U.S. Pat. No. 5,207,814, in suitable moulds, in accordance with what is described in Italian patent application MI92A02038 which can be referred to for any possible point of interest, can be linearly miniaturized into densified products which maintain the proportions of the mould with a precision greater than one part out of 10,000.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1A and 1B illustrate the configuration of the upper surface of the aerogel, and the corresponding surface of the densified product, respectively, of U.S. Pat. No. 4,680,049.
FIG. 2 illustrates an example of a profilometric determination of the present invention showing that the aspherical profile of the aerogel is comparable to the theonetical profile.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
In particular, therefore, the invention relates to the preparation of the above products, according to a process which involves the accurate geometrical definition of the aerogel by:
the cold filling of a suitable mould with a liquid colloidal dispersion, called sol, formed from specific chemical precursors;
the polycondensation of the sol to obtain gels (gelation);
the supercritical drying of the gels until aerogels are obtained with dimensions corresponding to the mould used;
the isotropic reduction (miniaturization) of the amorphous monolithic aerogels thus obtained, consisting of silicon oxide alone or in the presence of one or more oxides of elements belonging to the III° to VI° Group of the Periodical Table and exceptionally also other groups.
These cold moulding techniques are based on the use of special specifically prepared moulds.
These moulds, having much greater dimensions than the manufactured article, have an internal volume which is defined as a “homothetic copy” of the “end”-product itself, which is characterized in terms of profilometric accuracy, surface roughness and scaling ratio with the product itself.
The product thus obtained has “almost final” dimensions i.e. it requires only an optical polishing with the conventional methods or, at the best, it has “final” dimensions i.e. it does not require any conventional optical processing.
The overall result of the present invention is therefore the economical production of optical components and devices made of silica glass or other optical glass using a new cold moulding technique based on specific sol-gel synthesis processes.
The present invention consequently relates to optical articles, components or devices, with “final” or “almost final” dimensions and completely isotropic, consisting of silicon oxide, either alone or in the presence of one or more oxides belonging to groups III to VI of the Periodic Table, and exceptionally also other groups, said optical articles, components or devices having dimensional precision which has tolerance to surface roughness and profilometric accuracy required for the visible and ultraviolet spectrum ranges, characterized in that said tolerance being between ½ and {fraction (1/10)} wave length corresponding to the range 0.350-0.02 micrometers and, preferably, equal to ¼ wave length corresponding on an average, in the visible range, to 0.275 micrometers.
The above and other operating details will be explained in the following illustrative examples which however do not restrict the scope of the present invention.
EXAMPLE 1
Preparation of Preforms of Pure Silica
An example is given of the preparation of silica glass disks, with a diameter of 2.5 cm and height of 1.0 cm, as preforms for optical lenses.
For this purpose, 80 ml of HCl 0.01N are added, under vigorous stirring, to 100 ml (0.44 moles) of tetraethylorthosilicate (TEOS) (molar ratio TEOS:H 2 O:HCl=1:10:1.8×10 −4 ).
After about 60 minutes a limpid solution is obtained and 52.8 g of colloidal silica powder (Aerosil OX50-Degussa) prepared from silicon tetrachloride by oxidation at high temperatures, is added, still under vigorous stirring, to this solution.
The mixture obtained is homogenized using ultrasounds for a duration of about ten minutes and then clarified by centrifugation.
The homogeneous dispersion obtained is poured into cylindrical containers of polyester with a diameter of 5.0 cm and height of 2.0 cm, which are hermetically closed, placed in an oven and maintained at 50° C. for 12 hours.
The gel which is obtained is suitably washed with ethanol and subsequently supercritically dried in an autoclave at a temperature of 300° C. or in any case higher than the critical temperature of the solvent.
An aerogel is obtained which is calcinated at a temperature of 800° C. in an oxidizing atmosphere.
During the heating, the residual organic products coming from the treatment in the autoclave are burnt.
The dimensions of the aerogel obtained are those of the internal volume of the initial cylindrical container.
The disk of silica aerogel, after calcination, is subjected to a stream of helium containing 2% of chlorine, at a temperature of 800° C. and for a duration of 30 minutes to remove the silanolic groups present; the aerogel disk is finally heated in a helium atmosphere to a temperature of 1400° C. for the duration of one hour so that the silica reaches complete densification and consequent miniaturization.
After cooling, the disk reaches the desired final dimensions (diameter 2.5 cm and height 1.0 cm), maintaining a homothetic ratio with the form of the initial aerogel determined by the initial mould.
The densified material has the same physicochemical characteristics as the silica glass obtained by melting (density=2.20; refraction index (at 587.56 nm)=1.4585; Abbe dispersion=67.6).
EXAMPLE 2
Duplication of Optical Surfaces
Moulds are prepared with an internal surface finished with optical specifications (surface roughness less than ⅕ with a wave length corresponding to less than 0.08 micrometers).
The internal volume of the moulds corresponds to a cylinder of 5.0 cm in diameter and 2.0 cm in height.
One of the bases of the cylinder consists of the optical surface to be duplicated.
A colloidal solution prepared by adding to the homogeneous solution, obtained as in example 1, a solution of ammonium hydroxide 0.1N, dropwise under stirring, until a pH of about 4-5 is reached, is poured into the moulds.
The moulds thus filled, are hermetically closed, placed in an oven and maintained at 20° C. for 12 hours.
The production of the gel and subsequent supercritical drying are carried out according to the procedure described in example 1.
The profilometric and surface roughness results, measured on the optical surface of the aerogel, have the same optical quality as the original surface with a roughness of less than 0.1 micrometres, corresponding to ⅕ average wave length of the visible spectrum range.
EXAMPLE 3
Aspherical Lenses
A mould has been designed for providing a preform for a flat/convex lens of which the convex surface corresponds to an aspherical surface defined by the general equation: X = cy 2 1 + 1 - ( K + 1 ) c 2 y 2 + Dy 4 + Ey 6 + Fy 8 + Gy 10
wherein the y axis of the equation corresponds to the optical axis of the lens.
The constants for the densified product, having a diameter of 15 mm±0.05 and height of 6.25 mm±0.10, are the following:
C=0.17364596
K=−1.000000
D=−0.000071
E=0.000022
F=−6.62323E −7
G=7.03174E −9
To obtain the specific dimensions of the densified product, a miniaturization factor was programmed equal to 2, which is equivalent to an internal mould volume with double dimensions with respect to the manufactured article desired.
The transformations for the new constants are:
C′=C/R
K′=K
D′=D/R 3
E′=E/R 5
F′=F/R 7
G′=G/R 8
The appropriate mould was prepared with machine tools having numerical control.
No optical finishing treatment was carried out on the surface of the mould, the objective of the experiment being the average profile of the aspherical lens rather than the optical finishing of the surface.
A silicic sol was prepared with the procedure of example 2.
A series of 3 aerogels was prepared using the above mould according to the procedures described in example 2.
The aerogels were subjected to profilometric analysis as follows: each aerogel was placed in line at the centre of a Mitutoyo series 332 profile projector and compared to the theoretical profile corresponding to the equation of the aspherical profile.
The comparison was carried out by direct placement over the screen.
To increase the sensitivity of the method, each analysis was carried out with photographic aid and subsequent projection on a huge screen providing a sensitivity of up to a ten thousandth of the dimension of the object.
The aerogels were then densified (miniaturized), with the thermal treatment described in example 1 and compared with the respective theoretical profile as in the case of the aerogels.
In both the aerogels and the densified products, the maximum deviation, relating to the respective theoretical profiles is less than 0.002 mm, a value which is considered as the limit of the sensitivity of the method.
An example of profilometric determination is shown in FIG. 2 wherein the aspherical profile of the aerogel is comparable to the theoretical profile generated by the equation (see the dark external line) and the site of the theoretical profile points has been slightly moved towards the outside to facilitate observation of the trend parallel to the surface.
In addition to the profilometric analysis, the dimensional reproducibility was verified, by micrometry, on the main diameters (flat surface) of the densified products.
The results are summarized in Table 1 below:
TABLE 1
SAMPLE
AVERAGE DIAMETER (mm)
STAND. DEVIATION
A 34/44-1
15.3775
0.003
A 34/26
15.3725
0.002
A 34/28
15.3780
0.003 | An optical article, which is a preform for an optical lens, which is isotropic, consisting essentially of silicon oxide or silicon oxide in combination with one or more oxides of elements belonging to Groups III to VI of the Periodic Table,
the article having a dimensional precision which has tolerance to surface roughness and profilometric accuracy required in the spectral interval of 200-800 nm of the electromagnetic spectrum,
the tolerance being between one-half and one-tenth wavelength corresponding to the range of about 0.350-0.02 μm. | 2 |
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent application Ser. No. 13/680,596 (Attorney Docket No. 41507-707.401), filed Nov. 19, 2012, which is a divisional of U.S. patent application Ser. No. 12/498,752 (Attorney Docket No. 41507-707.201), filed Jul. 7, 2009, which claims priority to Provisional Application No. 61/080,742, (Attorney Docket No. 41507-707.101), filed Jul. 15, 2008, and Provisional Application No. 61/083,111 (Attorney Docket No. 41507-708.101), filed Jul. 23, 2008, the disclosures of which are incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention. The present invention relates generally to the fields of systems and methods for implanting an intravascular implant device, and more specifically to systems and methods for implanting embolic coils.
BRIEF SUMMARY OF THE INVENTION
[0003] Coil embolization is a commonly practiced technique for treatment of brain aneurysm, arterio-venous malformation, and other conditions for which vessel occlusion is a desired treatment option, such as, for example, in the occlusion of a tumor “feeder” vessel. A typical occlusion coil is a wire coil having an elongate primary shape with windings coiled around a longitudinal axis. In the aneurysm coil embolization procedure, a catheter is introduced into the femoral artery and navigated through the vascular system under fluoroscopic visualization. The coil in the primary shape is positioned within the catheter. The catheter distal end is positioned at the site of an aneurysm within the brain. The coil is passed from the catheter into the aneurysm. Once released from the catheter, the coil assumes a secondary shape selected to optimize filling of the aneurysm cavity. Multiple coils may be introduced into a single aneurysm cavity for optimal filling of the cavity. The deployed coils serve to block blood flow into the aneurysm and reinforce the aneurysm against rupture.
[0004] One form of delivery system used to deliver an embolic coil through a catheter to an implant site includes a wire and a coil attached to the wire. The coil (with the attached wire) is advanced through a catheter as discussed above. To release the coil into an aneurysm, current is passed through the wire, causing electrolytic detachment of the coil from the wire. A similar system is used to deliver a coil to the site of an arterio-venous malformation or fistula. The subject system provides a mechanical alternative to prior art electrolytic detachment systems.
BRIEF DESCRIPTION OF THE DRAWINGS
[0005] FIG. 1 is a side elevation view of an embolic coil implant system;
[0006] FIG. 2 is a side elevation view of the embolic coil of the implant system of FIG. 1 ;
[0007] FIG. 3A-3C are a series of side elevation views of the portion of the coil identified by region 3 - 3 in FIG. 2 , illustrating the properties of the pre-tensioned stretch resistant wire.
[0008] FIG. 4A illustrates the proximal portion of the coil engaged with the distal portion of the detachment shaft and wire.
[0009] FIG. 4B is similar to FIG. 4A and illustrates the proximal portion of the coil and the distal portion of the shaft and wire following detachment.
[0010] FIGS. 5A through 5G are a sequence of drawings schematically illustrating the steps of occluding an aneurysm using the system of FIGS. 1 through 4B .
[0011] FIGS. 6A and 6B schematically illustrate steps of detaching the coil from the detachment shall and wire in accordance with the method of FIGS. 5A through 5G .
[0012] FIG. 7 is an elevation view of an alternate embodiment of a detachment system, in which the distal end of the pusher tube is shown partially transparent.
[0013] FIG. 8 is a perspective view of the embodiment of FIG. 7 .
[0014] FIG. 9 is a plan view of the system of FIG. 7 , showing the coil detached from the pusher tube.
[0015] FIG. 10 is an elevation view of the system of FIG. 7 , showing the coil detached from the pusher tube.
[0016] FIG. 11 is a side elevation view of yet another embodiment of a detachment system according to the invention, in which the distal end of the pusher tube is shown partially transparent.
[0017] FIG. 12 is a plan view of the embodiment of FIG. 11 .
[0018] FIG. 13 is a bottom view of the embodiment of FIG. 11 .
[0019] FIG. 14 is a side elevation view of the embodiment of FIG. 11 following a step in detachment of the embolic coil.
[0020] FIG. 15 is a side elevation view of the embodiment of FIG. 11 following detachment of an embolic coil.
[0021] FIG. 16 is a side elevation view of yet another alternative embodiment according to the invention.
DETAILED DESCRIPTION OF THE INVENTION
[0022] Referring to FIG. 1 , general components of an embolic coil implant system 10 include a microcatheter 12 , insertion tool 14 , and embolic coil 16 . These components may be provided individually or packaged together. Additional components of the system may include a guide catheter insertable into the vasculature via an access point (e.g., femoral puncture), and an associated guide wire for facilitating advancement of the guide catheter.
[0023] Microcatheter 12 is an elongate flexible catheter proportioned to be received within the lumen of a corresponding guide catheter and advanced beyond the distal end of the guide catheter to the cerebral vasculature where an aneurysm to be treated is located. Suitable dimensions for the microcatheter include inner diameters of 0.010″ to 0.045″, outer diameters of 0.024″ to 0.056″, and lengths from 75 cm to 175 cm. One preferred embodiment utilizes the following dimensions: 0.025 in ID, 0.039 in Distal OD (3 F), 0.045 in Proximal OD (3.5 F), and length of 145-155 cm. Marker bands 18 facilitate fluoroscopic visualization of the microcatheter position during the course of an implantation procedure. Microcatheter 12 includes a lumen 20 proportioned to receive the embolic coil 16 and the shaft of the insertion tool 14 . When the coil is within the lumen of the microcatheter, the surrounding lumen walls restrain the coil in the generally elongated shape shown in FIG. 1 . Release of the coil from the microcatheter allows the coil to assume its secondary shape.
[0024] Details of the embolic coil 16 are shown in FIG. 2 . Coil 16 is formed of a wire 22 coiled to have a primary coil diameter D1 of approximately 0.020 inches, although smaller diameters, and diameters as large as 0.035 inches, may instead be used. The pitch of the coil may be uniform as shown, or it may vary along the length of the coil, or different sections of the coil may be formed to have different pitches. The wire material selected for the coil is preferably one capable of fluoroscopic visualization, such as Platinum/Iridium, Platinum/Tungsten, or other suitable material. In one embodiment, the wire forming the coil has a diameter of approximately 0.0015-0.0020 inches. Coil 16 is then formed into a secondary three-dimensional shape. The secondary shape can be helical, spherical, multi-lobal or any other shape desired to fill the aneurysm void. ‘The process for forming this shape is to temperature set the stretch resistant wire 30 into the desired shape. The stretch-resistant member could be a shape-memory polymer or metal such as nitinol. Stretch-resistant member 30 can be in a diameter range of 0.0005″ to 0.003″.
[0025] One or more reduced-diameter windings 24 are positioned at the proximal end of the coil 16 , forming a stop 26 . An atraumatic distal tip 28 , which may be formed of gold or tin solder or other material, is mounted to the distal end of the coil 16 . A stretch resistant wire 30 or other type of elongate filament or strand is attached to the distal tip 28 and extends through the coil 16 . Stretch resistant wire 30 includes an element 32 on its proximal end that is sufficiently broad that it will not pass through the lumen of the windings of stop 26 , but will instead rest against the stop 26 . Element 32 may be a ball (e.g., formed of gold/tin solder, PET, platinum, titanium or stainless steel) as shown, or an alternative element having features that will engage with or be unable to pass the stop 26 or other parts of the proximal portion of the coil 16 . The stretch resistant wire helps to maintain the pitch of the coil even when the coil is placed under tension. During implantation, the stretch resistant wire helps in repositioning of the coil (if needed). The stretch resistant wire makes the coil easier to retract, and maintains close positioning of coil windings during manipulation of the coil.
[0026] Stretch resistant wire 30 is pre-tensioned, so that the ball 32 naturally sits firmly against the stop 26 as shown in FIG. 3A . When tension is applied to the wire 30 as shown in FIG. 3B , and then released as in FIG. 3C , the ball will return to its firm seating against the stop. The stretch resistant wire prevents the coil from stretching when deployed, repositioned, or withdrawn from the aneurysm. This stretch resistant wire will not yield when placed in tension during repositioning. Conversely, stretch resistant wire will prevent compaction of adjacent coils, likely improving long term performance of coil 16 following implantation. Stretch resistant wire 30 will have a yield strength approximately 0.5 lbs. In a preferred embodiment, the stretch resistant wire is shape set to give the embolic coil 16 its predetermined secondary shape. In other words, the shape set of the wire will cause the coil 16 to assume the secondary shape ( FIG. 5C ) once it is advanced from the microcatheter 12 . In alternative embodiments, the coil itself, or both the coil and the wire may be shape set to give the coil its secondary shape.
[0027] Referring again to FIG. 1 , insertion tool 14 includes a flexible elongate tubular shaft 34 , and a handle 36 on the proximal portion of the shaft 34 . An actuator 38 on the handle 36 is manipulatable by a user to effect detachment of an embolic coil from the shaft 34 as will be discussed in detail below. Although the actuator is shown in this drawing as a slidable button, any number of other types of slidable, rotatable, pivotable, depressible, etc., actuators may instead be used using techniques well known in the art. Although the handle 36 is shown coupled to insertion tool 14 , in other embodiments, the handle 36 may be attached and removed for use with multiple coils to effect detachment.
[0028] FIGS. 4A and 4B show cross-section views of the distal portion of the shaft 34 . As shown, a detachment wire 40 or other type of elongate filament or strand extends through the lumen of the shaft 34 . During use, shaft 34 would be inserted through microcatheter 12 to the aneurysm. A pair of engaging elements 42 is positioned on the wire 40 . Engaging elements 42 are elements that will couple the detachment wire 40 to the stretch resistant wire 30 , preferably by engaging the element 32 . In the illustrated embodiment, the engaging elements 42 are spaced apart elements having a broader diameter than the wire. Suitable examples include spaced apart beads 42 deposited onto the wire. These may be formed of gold/tin solder, PET, stainless steel, or alternate materials.
[0029] As shown in FIG. 4A , embolic coil 16 is coupled to the insertion tool 14 by positioning ball 32 between the engaging elements 42 within the shaft 34 . The ball 32 is constrained between the engagement elements 42 and the surrounding walls of the shaft lumen. This positioning retracts the ball 32 proximally relative to the coil 16 , adding tension to the stretch resistant wire 30 .
[0030] Referring to FIG. 4B , to release the embolic coil 16 from the insertion tool 14 , the actuator is manipulated to cause relative advancement of the detachment wire 40 relative to the shaft 34 . In other words, the actuator may withdraw the shaft and/or advance the wire 40 . Other embodiments may be provided without an actuator, in which case the user may manually advance the wire 40 and/or retract the shaft 34 . The more proximal sections of the wire 40 and/or shaft 34 may be thicker than the distal sections as shown in FIGS. 6A and 6B to facilitate manual actuation by the user's fingers or by an actuator.
[0031] The relative movement between the shaft and wire causes the distal portion of the wire 40 to extend from the shaft, thereby releasing the constraints on the ball 32 . The ball 32 and attached stretch resistant wire 30 retract towards the coil 16 , and the ball 32 comes to rest at the stop 26 .
[0032] FIGS. 5A through 5G illustrate use of the system to implant the coil 16 . Prior to implantation, the coil is coupled to the insertion tool 14 as illustrated in FIG. 1 .
[0033] The microcatheter 12 is introduced into the vasculature using a percutaneous access point, and it is advanced to the cerebral vasculature. As discussed above, a guide catheter and/or guide wire may be used to facilitate advancement of the microcatheter. The microcatheter is advanced until its distal end is positioned at the aneurysm A. FIG. 5A .
[0034] The coil 16 is advanced through the microcatheter 12 to the aneurysm A. FIG. 5B . The coil and insertion tool may be pre-positioned within the microcatheter 12 prior to introduction of the microcatheter 12 into the vasculature, or they may be passed into the proximal opening of the microcatheter lumen after the microcatheter has been positioned within the body. The insertion tool 14 is advanced within the microcatheter 12 to deploy the coil from the microcatheter into the aneurysm A. As the coil exits the microcatheter, it assumes its secondary shape as shown in FIG. 5C due to the shape set of the stretch resistant wire 30 .
[0035] Referring to FIG. 6A , the detachment wire 40 may include fluoroscopically visible markers that indicate to the user when the coil has been advanced sufficiently for detachment. For example, the user may watch for alignment of a marker 44 on the wire 40 with the markers 18 on the microcatheter. Note, however, that the detachment step may be performed with the proximal end of the coil inside or outside the microcatheter.
[0036] At the appropriate time, the coil is released from the insertion tool by withdrawing the shaft 34 relative to the detachment wire 30 to cause the distal end of the wire to extend from the shaft 34 . FIGS. 5D and 6B illustrate retraction of the shaft 34 while holding the wire 30 stationary, although the detachment may instead be performed by advancing the wire while holding the shaft stationary, or by combined motion of retracting the shaft and advancing the wire. The coil detaches from the wire 30 , and the ball 32 of the coil 16 retracts into contact with the stop 26 . FIG. 5E . The insertion tool 14 is withdrawn from the microcatheter 12 . FIG. 5F . If additional coils are to be implanted, an insertion tool 14 with an attached coil is passed into the microcatheter 12 and the steps of FIGS. 5B through 5E are repeated. The method is repeated for each additional coil need to sufficiently fill the aneurysm A. Once the aneurysm is fully occluded, the microcatheter 12 is removed. FIG. 5G .
[0037] FIGS. 7-10 illustrate an alternative embodiment of an insertion tool 114 that may be used to deploy the embolic coil 16 in the manner similar to that shown in FIGS. 5A-5G .
[0038] Referring to FIG. 7 , the insertion tool 114 comprises an elongate pusher tube 116 having a tubular distal tip 118 (shown partially transparent in FIG. 7 ). A fulcrum 120 having a slot 122 (best shown in FIG. 9 ) is cut into a side wall of the distal tip 118 . The distal end of the fulcrum can be moved into an inwardly-extending position in which it extends into the lumen of the distal tip 118 as shown in FIGS. 7 and 8 . The fulcrum 120 is shape set to return to an open (or neutral) position generally flush with the pusher tube wall ( FIG. 9 ) when it is released from the inwardly-extending position. A pull wire 126 is extendable through the lumen of the pusher tube 116 and into the slot 122 in the fulcrum 120 to retain the fulcrum in the inwardly-extending position shown in FIGS. 7 and 8 .
[0039] The distal tip 118 is preferably formed of shape memory material such as nitinol, shape memory polymer, or an injection molded material having elastic properties. The more proximal sections of the pusher tube 116 can be made of polymeric tubing, with the distal tip 118 mounted to polymeric tubing. In the illustrated embodiment, the distal tip 118 includes a plurality of proximally-extending fingers 124 laminated into the polymeric tubing of the pusher tube 116 to secure the distal tip in place.
[0040] To couple the pusher tube 116 and coil 16 for use, the pull wire 126 is introduced into the pusher tube. Ball 32 is separated slightly from the coil 16 and is inserted into the pusher tube 116 and held in place while the fulcrum 120 is pressed into the inwardly-extending position to prevent movement of the ball 32 out of the distal tip 118 . The pull wire 126 is passed through the slot 122 to retain the fulcrum in the inwardly-extending position.
[0041] To deploy the coil 16 , the coil and pusher tube 116 are passed through a delivery catheter as described above. At the site of the aneurysm, the pusher tube 116 is advanced to push the coil out of the delivery catheter. The pull wire 126 is pulled proximally from the slot 122 of the fulcrum 120 , allowing the fulcrum 120 to return to its open position and out of contact with the ball 32 . As with the previous embodiments, the ball 32 retracts into contact with the proximal end of the coil 16 and in doing so exits the proximal end of the pusher tube 116 .
[0042] FIGS. 11-15 illustrate another alternate embodiment of a detachment system. FIGS. 11 , 14 and 15 illustrate detachment system 200 following successive steps to detach embolic coil 206 from insertion tool 214 . Beginning with FIG. 11 , a side elevation view of the distal end of insertion tool 214 is shown as partially transparent. Insertion tool 214 comprises an elongate pusher tube 216 having a tubular distal tip 218 , and side wall 204 defining lumen 208 therethrough. Side wall 204 is cut, molded, or otherwise configured to define paddle 240 , partial aperture 244 surrounding a portion of paddle 240 , and shoulder 246 . Paddle 240 and partial aperture 244 may be of various alternative sizes and/or shapes. An example of a suitable shape for paddle 240 can be seen in a plan view in FIG. 12 , which also reveals a possible position of ball 232 prior to deployment of system 200 . As explained in greater detail below, prior to deployment of system 200 to release coil 206 , ball 232 has freedom of movement within lumen 208 , both axially and rotationally. The exact position of ball 232 will consequently vary from that illustrated in FIG. 12 .
[0043] Also cut or otherwise configured or disposed upon a side wall 204 is alignment member 228 , shown in the example of FIG. 11 as opposite paddle 240 . As seen from a bottom view of the device in FIG. 13 , alignment member is illustrated as a loop cut from sidewall 204 . Alternatively, an alignment member may be formed by placing one or more circumferential cuts into the sidewall to define a band and bending the band inwardly into the lumen. It will be appreciated that alignment member 228 may alternatively be, for example, a hook, tab, or any other suitable structure for guiding the position of pull wire 226 . Pull wire 226 is axially moveable within alignment member 228 , however, alignment member 228 helps prevent unintended longitudinal translation of pull wire 226 .
[0044] In preparation for deploying system 200 , pull wire 226 is loaded through alignment member 228 , through lumen 208 , until it reaches ball 232 , or as far as coil 206 . Prior to loading coil 206 , pull wire 226 , which may be tapered, may be threaded through the distal end of insertion tool 214 to permit loading of ball 232 , and then retracted slightly to releasably retain coil 206 . When positioned within distal tip 218 via alignment member 228 , and occupying lumen 208 pull wire 226 urges ball 232 against paddle 240 , and ball has freedom of movement within aperture 244 . Partial aperture 244 permits paddle 240 to be urged slightly out of the plane of sidewall 204 , and paddle 240 in turn places some pressure on ball 232 . Ball 232 is prevented by shoulder 246 from exiting the distal tip 218 . Though ball 232 is retained within distal tip of insertion tool 214 prior to deployment of system 200 , ball 232 advantageously has both axial and rotational freedom of movement within the distal tip 218 of insertion tool 214 prior to retraction of pull wire 226 by an operator.
[0045] As shown in FIG. 14 , during deployment of detachment system 200 , pull wire 226 is retracted proximally of ball 232 . (Alternatively, insertion tool 214 may be moved distally to pull wire 226 .) Once pull wire 226 is proximal of ball 232 , ball 232 is urged by paddle 240 into the lumen 208 of insertion tool 214 . Axial movement of ball 232 is no longer restricted in a distal direction by shoulder 246 , and ball 232 (and hence coil 206 ) is free to exit distal tip 218 . FIG. 15 illustrates coil 206 following its exit from distal tip 218 .
[0046] FIG. 16 illustrates a similar detachment mechanism which operates generally according to the same principles of the embodiment described in relation to FIGS. 11-15 above. However, in the embodiment illustrated in FIG. 16 , paddle 340 is oriented perpendicularly to the longitudinal access of insertion tool 214 . Further, no aperture surrounds paddle 340 . Other, alternative configurations of paddle 340 are also possible according to the invention. | Embolic coil implant systems and methods whereby coils are mechanically detachable are disclosed. The coils include a retention element that may be releasably retained within the distal end of an implant tool. The implant tool may include a fulcrum configured to engage a first filament and prevent the release of the coil when the first filament is engaged. Alternatively, an urging means and aperture may be disposed within the sidewall of the implant tool, and a first filament may, in conjunction with the aperture and sidewall, releasably retain the coil until the first filament is withdrawn. The implant tool may also include an alignment member for aligning the first filament. | 0 |
REFERENCE TO PRIOR APPLICATION
This application claims the priority of provisional application 61/135,842, filed Jul. 22, 2008 entitled HAIR BRUSH WITH SLIDEABLE BRUSH HEAD by Mary Asta.
BACKGROUND OF THE INVENTION
The present invention relates, generally, to the field of hairbrushes, and specifically toward a hairbrush having elongated handles that can be used in different ways. Hairbrushes are extremely conventional for use in grooming hair as well in styling the hair. Typically, a hairbrush is constructed of a handle and a brush head having bristles thereon of varying thicknesses and stiffness for use with a variety of hair types to achieve various styles.
U.S. Pat. No. 1,951,023 discloses a brush including a handle having a mass of sponge rubber secured thereto. The handle is disclosed to be collapsible and is composed of two or more telescoping members one of which is embedded within the mass of the sponge rubber with an inner member being slideable into and out of an embedded member to form other convenient extending handles.
U.S. Pat. No. 2,641,012 illustrates a brush that has telescoping handle parts that form extendable sections of a hairbrush One part of the handle section has a larger diameter while other sections are progressively smaller whereby the various sections can telescope within each other to form a longer or shorter handle.
U.S. Pat. No. 3,690,331 discloses a combined brush and comb including a body having tufts on an exterior surface of the body and a comb that may be adjusted for various angles with respect to the body of the brush and included are retractable handles. In one embodiment the handles are extendible from either end of the brush body to facilitate its use by either a right-handed or a left-handed person.
BRIEF DESCRIPTION OF THE INVENTION
The inventive concept of the instant invention hereby disclosed is a specific hairbrush that includes a handle upon which a grooming roller can be moved from one end of the handle to the other depending on the needs of the beautician due to styling requirements or mere left- or right-handedness. The concept also allows for the grooming roller to be moved from end to the other, or removed altogether, during styling in order to provide a space for another hairbrush having a different circumferential size or different brushing elements as long as the inner diameter remains the same so as to conform to the outer diameter of the handle.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1A is a side view of the brush head of the instant invention.
FIG. 1B is a top view of the brush head of the instant invention.
FIG. 1C is a side view of the handle of the instant invention.
FIG. 1 is an exploded view of the brush head of the preferred embodiment of the instant invention.
FIG. 1D is the view show in FIG. 1 , but intact and not exploded.
FIG. 2B is a cross-sectional side view of an alternate embodiment of the instant invention.
FIG. 2A is similar to FIG. 2B , but with the mechanism activated.
FIG. 3 is an exploded view of a second alternate embodiment of the instant invention.
FIG. 3A is a side view of the handle of the second alternate embodiment of the instant invention.
FIG. 3B is a top view of the handle of the second alternate embodiment of the instant invention.
FIG. 3C is a cross sectional view of the handle of the second alternate embodiment of the instant invention.
FIG. 3D is a perspective view of the brush head of the second alternate embodiment of the instant invention.
FIG. 4 is a side view of the third alternate embodiment of the instant invention.
FIG. 4A is a cross sectional side of the third alternate embodiment of the instant invention.
DETAILED DESCRIPTION OF THE INVENTION
FIGS. 1A-1D illustrate a first embodiment that discloses a hair brush having hair brush head 1 with bristles 2 thereon. The hair brush head 1 consists of two halves 1 a , 1 b that form an internal chamber that can snugly house an elongated slideable handle 9 that can move the brush head 1 from one end of the handle 9 to the other and can be locked thereat. The two halves of the brush 1 have contained therein in a groove 4 at either end a flexible ring 3 . The flexible ring 3 has push buttons 5 which, when the two halves 1 a , 1 b are assembled, fit in a hole 7 formed by the two halves 1 a , 1 b . The flexible ring 3 further has two inwardly directed arrest buttons 6 . The operation of this embodiment is such that if the brush head 1 is located on one end of the handle and locked into place by the arrest buttons 6 after having penetrated into the openings 8 in the handle, the operator merely has to push the two push buttons 5 inwardly thereby flexing the ring 3 , which will then release the two arrest buttons 6 from the holes or opening 8 in the handle 9 , and the brush head 1 can be moved to the other end of the handle 9 . When the pressure on the push buttons 5 is released, the two arrest buttons on the other end of the brush head 1 will settle back again into the holes 8 on the handle 9 and the brush head 1 will be relocated to the other end of the handle.
FIGS. 2 and 2A show a second embodiment of how a brush head 1 can be locked in place at either end of a handle 20 . In this embodiment there are shown two end push buttons 1 a and 1 b at either end of the handle 20 . Each one of the push buttons 1 a , 1 b is connected to activating rods 21 , 22 . Each inner end of the activating rods 21 and 22 are now connected to a rotating lever 23 , which can rotate around a pin 23 a in the inner confines of the handle 1 . The outer ends of the rotating lever 23 keep balls 25 , 26 at an opening in the hair brush head 1 in an arrested position. The rotating lever 23 is kept in this position and in contact with the balls 25 , 26 by a coil spring 24 . When it is desired to move the brush head 1 from one end of the handle 20 to the other, it is merely up to the operator to push one of the end push buttons 1 a , 1 b inwardly, thereby activating the respective rod 21 , 22 causes the rotating lever 23 to rotate to some extent and, whereby, the pressure on the balls 25 , 26 will be released and the brush head 1 can be moved. Upon release of the pressure from either push button 1 a , 1 b , the balls 25 , 26 will again lock into an opening at the end of the brush head 1 and lock the same into place because of the resetting of the lever 23 .
FIGS. 3-3D illustrate a similar embodiment as was explained with regard to FIGS. 2A-2D . At either end of the hollow handle halves 2 a and 2 b there are again two push buttons 36 , 37 which again, like in FIG. 2 , each operate on an activating rod 34 , 35 . The ends of each of the activating rods 34 , 35 are connected to a rotating disc which has dimples at its outer periphery to accept two arresting balls 31 , 32 . In an activated position the two balls will enter two openings at the ends of the brush head 1 to lock it in place. Again, as explained in FIG. 2 , there is a coil spring (not shown) that keeps the disc in an activated position and thereby the balls 31 , 32 in a locked position. Upon pushing either one of the push buttons 36 , 37 , the respective activating rod 34 , 35 will rotate the disc 30 and take the balls 31 , 32 out of engagement with one of the holes 33 , (seen in FIG. 3D , at the end of the brush head 1 ) and the brush head 1 can now be moved to the other end of the handle 20 .
FIG. 4 illustrates still another embodiment of how a brush head 1 can be moved to the other end of the handle 20 . At both ends of the handle 20 there are two respective push buttons 40 , 41 . Each one of the push buttons 40 , 41 is connected to a respective sliding sleeve 42 , 43 . Each of the sliding sleeves 42 , 43 have a sleeve-like end at their inner ends. In the middle of the interior of the hollow handle there is located a flexible activating element 45 that has camming surfaces 44 , 46 at its outer ends. The camming surfaces 44 , 46 can be overridden or overlapped by each of the sleeve-like inner ends of the sliding sleeves 42 , 43 . A centering spring 51 is located inside the flexible activating element 45 and also extends to the insides of each of the sliding sleeves 42 , 43 . The flexible activating element 45 has two outwardly extending protrusions 47 , 48 which normally are engaged with arresting holes 49 , 50 at each of the ends of the brush head 1 . When it is desired to move the brush head 1 from one end of the elongated handle 20 to the other end, the operator can push either push button 40 or 41 whereby either sliding sleeve 42 , 43 with its sleeve-like inner end will ride over either the camming surfaces 44 , 46 of the flexible activating element 45 to thereby distort the flexible activating element 45 and take the protrusions 47 , 48 out of engagement with the arresting holes 49 , 50 at either end of the brush head 1 and release the same to be moved to the other end of the handle 20 .
The rollers can also contain a head-conducting material, such as copper, to allow the rollers on the brush to act like hot rollers when used with a heat source, such as a blow dryer.
The discussion included in this patent is intended to serve as a basic description. The reader should be aware that the specific discussion may not explicitly describe all embodiments possible and alternatives that are implicit. Also, this discussion may not fully explain the generic nature of the invention and may not explicitly show how each feature or element can actually be representative or equivalent elements. Again, these are implicitly included in this disclosure. Where the invention is described in device-oriented terminology, each element of the device implicitly performs a function. It should also be understood that a variety of changes may be made without departing from the essence of the invention. Such changes are also implicitly included in the description. These changes still fall within the scope of this invention.
Further, each of the various elements of the invention and claims may also be achieved in a variety of manners. This disclosure should be understood to encompass each such variation, be it a variation of any apparatus embodiment, a method embodiment, or even merely a variation of any element of these. Particularly, it should be understood that as the disclosure relates to elements of the invention, the words for each element may be expressed by equivalent apparatus terms even if only the function or result is the same. Such equivalent, broader, or even more generic terms should be considered to be encompassed in the description of each element or action. Such terms can be substituted where desired to make explicit the implicitly broad coverage to which this invention is entitled. It should be understood that all actions may be expressed as a means for taking that action or as an element which causes that action. Similarly, each physical element disclosed should be understood to encompass a disclosure of the action which that physical element facilitates. Such changes and alternative terms are to be understood to be explicitly included in the description. | A hair brush with a slideable brush head that allows the brush head to be positioned on either end of the elongated handle to thereby providing ease of use by both right handed or left handed users. The elongated handle has different ways thereon to arrest the brush head in any desired position. The brush head may also be removed from the handle, if so desired, so that a brush head of a different circumference but the same inner diameter may be used. | 0 |
FIELD OF THE INVENTION AND RELATED ART
[0001] The present invention relates to a liquid ejection recording head for placing liquid such as ink on recording medium such as paper.
[0002] In the field of a printing apparatus, in particular, a printing apparatus which employs an inkjet method, improvement in quality and/or speed in color recording is one of the important themes.
[0003] In order to improve recording quality, it is necessary for a recording head to eject ink droplets as small as possible. In order to improve recording speed, it is necessary for an ink supply path to be smooth and stable in its ink delivery performance.
[0004] The ink ejecting performance of a recording head which ejects small ink droplets is easily affected by foreign objects which have entered the recording head. Thus, in order to prevent foreign objects from entering the recording head, the recording head is provided with a filter, which is placed in the ink path of the recording head.
[0005] It is common knowledge that, generally, when a recording head and an ink container are integrated in the form of a cartridge, a filter is placed in a certain position in the ink supply path between the ink container and recording head, whereas when a recording head is rendered independent from an ink container, a filter is placed at one end of the ink supply tube which connects the recording head and ink container.
[0006] Shown in FIGS. 3 and 4 is the structure of the ink inlet portion of a conventional recording head, in which the recording head and ink container are independent from each other. Referring to FIG. 4, which is a sectional view of both the recording head 41 and ink container 42 , the ink container 42 comprises: an external shell with an air vent 422 and an ink outlet 421 ; an absorbent member 423 stored in the shell: and a pressing member 307 placed in contact with the ink outlet 421 for guiding outward the ink within the ink container 42 . The recording head 41 is provided with a liquid inlet 301 (ink supply tube), which is a part of a liquid guiding path 301 for supplying ink to an ink ejecting portion 411 . The outward end of the liquid inlet 301 (liquid guiding path 302 ) is provided with a filter 303 , the center portion of which protrudes slightly outward of the liquid inlet 301 .
[0007] [0007]FIG. 3 is an enlarged sectional view of the outward end portion of the liquid guiding path 302 , the ink outlet 421 , and their adjacencies. Referring to FIG. 3( c ), conventionally, the ink outlet 421 of the ink container is provided with the pressing member 307 , and the ink is supplied to the recording head through the contact between the filter 303 and pressing member 307 . Next, referring to FIG. 3( b ), generally, the filter 303 is located at the outermost end of the ink guiding path 302 , the periphery of the filter 303 being covered with resin, as disclosed in Japanese Laid-Open Patent Application 6-238910, to prevent the occurrences of such problems as the filter 303 becoming separated from the liquid inlet 301 , and the fiber ends exposed at the periphery of the filter damaging the pressing member. The filter 303 is fixed to the outermost end of the ink guiding path 302 by thermally bending inward the edge of the ink inlet of the recording head, which is formed of thermoplastic resin. When the filter is placed in a manner to directly press a highly elastic absorbent member as in the case of Japanese Laid-Open Patent Application 5-345425, there will be no problem. However, in the case of a structural arrangement in which the filter is placed in a manner to directly press the pressing member of an ink container, the following problem occurs. That is, if the thermoplastic resin portion of the ink inlet, covering the periphery of the filter, projects farther toward the pressing member than the filter, the resin portion comes into contact with the pressing member which is greater in diameter than the filter, preventing the filter from coming into contact with the pressing member. Thus, in such a case, the filter is shaped so that the center portion of the filter spherically bulges outward to assure that the center portion of the filter comes into contact with the pressing member (FIG. 3( b )). A conventional filter formed by weaving metallic fibers is flexible, but flat in its natural state. Thus, it is welded to the resin portion so that the center portion of the filter remains flexed outward of the liquid inlet. Since the filter is flexible, it deforms as it is pressed by the pressing member, preventing air from remaining (entering) between the filter and pressing member.
[0008] The filter grade should be selected according to the diameter of the orifices through which ink droplets are ejected. However, a conventional filter formed by weaving metallic fibers is not satisfactory in terms of foreign object removal performance. More specifically, in order to remove finer foreign objects, the metallic fibers must be made finer, and the finer the metallic fibers, the weaker the filter. In other words, it is difficult to make a filter which is strong and yet does not easily clog. Thus, in order to provide a filter which is strong and yet does not easily clog, it become necessary to replace the conventional filter material with such a material that is stronger and yet is less likely to clog than the conventional filter material. Thus, a filter formed by sintering metallic fibers layered like the fibers in nonwoven fabric has come into use as a replacement for a conventional filter, due to its advantage that it is finer in mesh and its multilayer structure makes it less likely to clog. On the other hand, a sintered filter lacks flexibility, and therefore, it is difficult to make the center portion of a sintered filter permanently protrude outward of the liquid inlet of a liquid ejection recording head when attaching the filter to the resinous portion of the liquid inlet. Thus, a sintered filter must be shaped so that its center portion permanently protrudes in the direction corresponding to the outward direction of the liquid inlet ink, prior to the attachment of the filter to the resinous portion of the liquid inlet. As for the shape in which the center portion of a sintered filter protrudes, in the case of a sintered filter with a small diameter, for example, no more than approximately 5 mm, the center portion of the sintered filter will be in the form of a circular frustum, being flat on top, surrounded by the flat peripheral portion of the filter, in consideration of the issues regarding the manufacturing of the sintered filter, for example, the accuracy in a pressing process.
[0009] Further, in the case of an ink supplying member which uses capillary force to supply ink, the higher the speed at which ink must be supplied, the stronger the ink retaining force of the ink supplying member must be, and the stronger the ink retaining force of the ink supplying member must be, the stronger the capillary force the ink supply member generates must be. Conventionally, a pressing member formed by layering polypropylene fibers in the same manner as the fibers in felt are layered has been used as the aforementioned pressing member. In the case of this type of pressing member, however, the needle punch marks which were made while manufacturing this type of pressing member, and/or the density limit in the manufacturing process, made it difficult to increase the capillary force in this type of pressing member higher than a certain level. Thus, a pressing member formed by parallelly binding polypropylene fibers in such a manner that the fiber direction matches the ink flow direction has come into use as a replacement for a conventional pressing member, due to its advantage that it is higher in fiber density, being therefore capable of generating stronger capillary force, and also, being capable of preventing the pressure loss from increasing.
[0010] However, the above described filter formed by sintering is poor in flexibility compared to the woven filter, it is difficult to sinter a filter capable of conforming to the contour of the pressing member as does a conventional woven filter. Further, compared to a conventional pressing member formed of felt, a pressing member formed of bound PP fibers is higher in density, and its fibers are perpendicular to the interface between the pressing member and filter. Therefore, the pressing member formed of bound PP fibers is not as flexible as a conventional filter, at the interface, failing to making satisfactory contact with a filter, as shown in FIG. 3( d ). In other words, when an liquid ejection recording head equipped with a sintered filter is used in combination with an ink container equipped with a pressing member formed of bound PP fibers, a new number of relatively large gaps are left between the filter and pressing member, as shown in FIG. 3( d ), adversely affecting the stability in ink delivery.
[0011] Thus, in terms of making the filter and pressing member properly contact each other, the configuration of the contact portions of the two components, and their positions relative to each other, are much more important than they used to be. Further, the contact pressure between the filter and pressing member must be properly adjusted. In other words, there is much to be improved regarding the filter for a liquid ejection recording apparatus, in terms of the stability in ink supply performance and yield in its mass production.
[0012] During an operation for restoring the performance of a liquid ejection recording head by suctioning away the ink in, or in the adjacencies of, the ejection orifices, ink flows at a higher speed than during a normal printing operation. Thus, if the filter and pressing member are not properly in contact with each other, it is possible that air will be sucked into the liquid guiding path. If air is sucked into the ink supply path by a large amount, the ink supply to the ejection orifices is interrupted, resulting in unsatisfactory printing performance.
SUMMARY OF THE INVENTION
[0013] In consideration of the above described problems, the primary object of the present invention is to keep the filter of the ink inlet of a liquid ejection recording head properly in contact with the virtually flat contact surface of the pressing member of a liquid supply container, in order to make it possible to provide a liquid ejection recording head superior in terms of the stability in ink delivery performance and also in terms of yield in its mass production.
[0014] The present invention for accomplishing the above objects relates to a liquid ejection recording head, which is provided with a filter attached to the entrance of the liquid guiding path of the recording head, and receives liquid from one or more ink containers, which are mounted on a carriage, and the liquid outlet of which comprises a pressing member, which is formed of fibers and contacts the filter of the recording head. The present invention is characterized in that the portion of the filter of the liquid ejection recording head, which contacts the pressing member of the ink container, projects outward of the ink guiding path of the recording head, relative to the periphery of the filter by which the filter is attached to the recording head, and is virtually flat. The present invention includes a liquid ejection recording head, the filter of which is such a filter that is produced by sintering metallic fibers.
[0015] With the provision of the above described structural arrangement, according to which the portion of the filter, which contacts the pressing member, projects more outward than the periphery of the filter by which the filter is attached to the recording head, is rendered flat. Therefore, the filter can be kept satisfactorily in contact with the virtually flat contact surface of the pressing member.
[0016] According to the present invention, a filter for the above described liquid ejection recording head may be such a filter that even before the filter is attached to the recording head, the center portion of the filter projects outward of the liquid guiding path of the recording head, relative to the periphery of the filter, and the center portion of the filter, which contacts the pressing member of an ink container, is virtually flat, or such a filter that before it is attached to the recording head, its center portion which comes into contact with the aforementioned pressing member, spherically protrudes outward relative to its periphery, but after the filter is fixed to the entrance of the liquid guiding path of the liquid ejection recording head, its center portion is made flat by pressing.
[0017] Further, in order to prevent air bubbles from entering a liquid ejection recording head due to a sudden change in ink flow speed, the diameter of the center portion of the above described filter is desired to be greater than the size of the cross-section of the liquid guiding path of the recording head, on the inward side of the filter.
[0018] These and other objects, features and advantages of the present invention will become more apparent upon a consideration of the following description of the preferred embodiments of the present invention taken in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0019] [0019]FIG. 1 is a sectional view of the ink inlet portion of an inkjet recording head, after the welding of the filter thereto, in the first embodiment of the present invention,
[0020] [0020]FIG. 1( b ) showing the state in which the filter has been deformed by being pressed, and
[0021] [0021]FIG. 1( c ) showing the state of the contact between the filter and pressing member.
[0022] [0022]FIG. 2 is a sectional view of the ink inlet portion of an inkjet recording head, and the filter therefor, in the second embodiment of the present invention,
[0023] [0023]FIG. 2( b ) showing the state after the welding of the filter thereto, and
[0024] [0024]FIG. 2( c ) showing the state of the contact between the filter and pressing member.
[0025] [0025]FIG. 3 is a sectional view of a conventional filter before its welding,
[0026] [0026]FIG. 3( b ) showing the state after the welding of the conventional filter, and
[0027] [0027]FIG. 3( c ) showing the state of the contact between the conventional filter and pressing member.
[0028] [0028]FIG. 4 is a schematic sectional view of the entirety of a cartridge, the recording head and ink container of which are independent from each other,
[0029] [0029]FIG. 4( a ) showing the state in which the recording head and ink container have been separated from each other, and
[0030] [0030]FIG. 4( b ) showing the state in which the recording head and ink container have been properly connected.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0031] Hereinafter, the preferred embodiments of tile present invention will be described in detail with reference to the appended drawings. Here, emphasis will be placed upon the arts in the present invention different from the conventional arts
[0032] (Embodiment 1)
[0033] [0033]FIG. 1 is a sectional view of the ink inlet portion of the recording head in the first embodiment of the present invention. The inkjet recording head in this embodiment has an ink inlet path (liquid flow path) 102 , which is in the cylindrical ink inlet 101 of the inkjet recording head. To the outward end of the ink inlet path 102 , a filter 103 has been thermally welded. More specifically, the outward end of the ink inlet is provided with two types of ribs (unshown) which are located at the peripheral portion of the outward end of the ink inlet path 102 . To the ribs of one type, the filter 103 is welded. The ribs of he other type covers the periphery of the filter 103 in a manner to wrap it. These ribs constitute the portions to which the filter 103 is fixed. The outward end of the ink inlet is also provided with a plurality of pillars, which are configured to support the filter 103 from the inward side of the filter 103 as the filter 103 is fixed to the outward end of the ink inlet by its periphery. Before the filter 103 is attached to the ink inlet of the recording head, its center portion spherically bulges in the direction correspondent to the outward direction of the ink inlet, whereas its peripheral portion is rendered flat. After the filter 103 is placed in the slightly recessed portion of the end portion of the ink inlet of the recording head, it is fixed to the outward end of the ink inlet portion, by thermally deforming the aforementioned ribs located at the periphery of the ink inlet, that is, those constituting the filter fixing portion (FIG. 1( a )).
[0034] Referring to FIGS. 1 ( b ) and 1 ( c ), after the filter 103 is welded to the ink inlet portion of the recording head, the center portion of the filter 103 , which is the portion of the filter 103 by which the filter 103 contacts the contact surface of the pressing member 107 formed of bound PP fibers, and is spherically protruding outward of the ink inlet of the recording head, is flattened by pressing. With this method, it is possible to give the filter 103 such a configuration that is impossible to realize unless the filter 103 is attached to the ink inlet of the recording head in accordance with the present invention. In other words, according to this embodiment of the present invention, the pressing member 107 and filter 103 can be properly placed in contact with each other regardless of the hardness of the contact surface of the pressing member 107 . The distance by which the center portion of the filter 103 is pressed is adjusted so that the portion of the center portion of the filter 103 , which will be flattened by pressing, will be outward of the peripheral portion of the filter 103 after the flattening.
[0035] The diameter of the ink inlet path, on the immediately inward side of the filter 103 , is rendered smaller than the diameter of the flat portion of the outward end of the ink inlet of the recording head, which the pressing member 107 contacts. Therefore, it is further assured that even when the velocity at which ink flows through the ink flow path suddenly changes due to the execution of the recording head performance recovery process in which ink is aggressively suctioned, air bubbles are not suctioned into the ink path.
[0036] (Embodiment 2)
[0037] [0037]FIG. 2 is a sectional view of the ink inlet of the recording head in the second embodiment of the present invention. The inkjet recording head in this embodiment is provided with a liquid inlet path 202 , which is located within the cylindrical ink inlet portion 201 of the recording head. The outward end of the ink inlet path 202 is provided with a filter 203 , which is thermally welded thereto. When a filter is large in diameter, it can be shaped so that its center portion protrudes outward in the form of a frustum, being flat at the center portion, before its thermal welding to the recording head. In other words, the portion of the outwardly protruding portion of the filter 203 , which contacts the pressing member, is rendered flat, eliminating the need for pressing the filter 203 to flatten its center portion after the welding of the filter 203 (FIG. 2( a )). Thus, in this embodiment, the filter 203 can be attached to the cylindrical ink inlet portion 201 of the recording head by thermally deforming the cover rib 205 after properly positioned the filter 203 , which is flat across its contact portion, or the center portion, relative to the ink inlet portion (FIG. 2( b )).
[0038] With the above described structural arrangement, the filter 203 and the pressing member 207 can be kept properly in contact with each other, regardless of the surface hardness of the pressing member 207 (FIG. 2( c )).
[0039] Incidentally, regarding the type of the inkjet recording heads in the preceding embodiments of the present invention, not only is the present invention applicable to an inkjet recording head which ejects liquid droplets from its nozzles by using the film boiling phenomenon which occurs as thermal energy is applied to liquid, but also an inkjet recording head which ejects liquid from its nozzles by using the microscopic displacement which occurs to elements in the form of thin film, as an electrical signal is inputted into the elements.
[0040] As described above, according to the present invention which relates to a liquid ejection recording head having a liquid inlet, through which the head is supplied with the liquid from the liquid outlet, comprising a pressing member formed of fibers, of an ink container, and a filter with which the liquid inlet is fitted, the filter is shaped like a frustum so that the portion of the filter, which contacts the pressing member, projects outward relative to the peripheral portion of the filter by which the filter is fixed to the liquid inlet, and also becomes virtually flat, making it possible for the filter to remain properly in contact with the flat contact surface of the pressing member. Therefore, it is possible to obtain a liquid ejection recording head which is reliable in terms of filter performance (regarding the capillary force of the pressing member), and is excellent in terms of the stability in ink supply.
[0041] The present invention is particularly effective when applied to a liquid ejection recording head which is connected to a liquid container, the pressing member of which is formed of parallelly bound fibers. Needless to say, it is not contradictory to the gist of the present invention to apply the present invention to a liquid ejection recording head which is connected to a liquid container, the pressing member of which is formed of relatively soft fibrous material such as felt.
[0042] Further, the present invention is effectively applicable to a liquid ejection recording head which employs a hard filter produced by sintering. However, the application of the present invention to a filter produced by weaving metallic fibers is not contradictory to the gist of the present invention, which is obvious.
[0043] Of various combinations between pressing members and filters, the combination which benefits most from the present invention is the combination of a pressing member formed of parallelly bound fibers, and a sintered filter. However, the present invention is also applicable to a combination of a pressing member formed of parallelly bound fibers, and a filter formed of woven metallic fibers, or a combination of pressing member formed of felt or the like, and a sintered filter or a metallic fiber filter.
[0044] While the invention has been described with reference to the structures disclosed herein, it is not confined to the details set forth and this application is intended to come such magnifications or changes as may come within the purpose of the improvements or the scope of the following claims. | A liquid ejection recording head which receives liquid from one or more liquid containers mounted on a carriage, the liquid container having a press-contact member of fibrous material at a liquid outlet, the liquid ejection recording head includes a tubular member for receiving ink from the liquid container, the tubular member being provided with an upstream edge with respect to a direction of flow of the liquid therethrough; a filter provided in the tubular member and having an outer surface press-contactable to the press-contact member, the outer surface being a substantially flat surface and being outward beyond the upstream edge of the tubular member. | 1 |
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims the benefit of U.S. Provisional patent application serial No. 60/447,543, filed on Feb. 14, 2003, the contents of which are hereby incorporated herein by reference.
[0002] The present application is also related to U.S. patent applications, attorney docket no. END-5016NP, Ser. No. [______] and END-5017NP, Ser. No. [______] filed concurrently herewith.
FIELD OF THE INVENTION
[0003] The present invention relates in general to the performance of a variety of surgical steps or procedures during surgical operations and, more particularly, to methods and apparatus for utilizing ultrasonic sensing as an integral part of such surgical procedures to expedite and facilitate their performance and to extend a surgeon's sense of “feel” within a body cavity.
BACKGROUND OF THE INVENTION
[0004] Two operations that commonly can be performed to advantage using hand assisted laparoscopic surgery (“HALS”) techniques are nephrectomy and bowel surgical repair. In both instances, a hand port is used in conjunction with one or more cannulas (trocars) that permits introduction of a combination illuminating and viewing instrument and a number of different endoscopic surgical instruments. The endoscopic instruments perform surgical steps or procedures required to complete the surgical operation prior to removing the cannulas and closing the relatively small openings required for their insertion.
[0005] A problem in using certain surgical instruments that is particularly apparent during endoscopic surgery is the lack of the surgeon's sense of feel and easy access to all internal body cavity locations. In non-endoscopic surgery (i.e. open surgery), a surgeon can normally easily verify the identification of structures or vessels within a conventional open surgery incision. In particular in the two noted operations, the surgeon normally uses the sense of feel to verify the nature of visually identified operational fields.
[0006] In a gall bladder operation, for example, the bile duct must be distinguished from a blood vessel that passes close to the duct. Also, the locations of blood vessels must be determined in the repair of an abdominal hernia using endoscopic surgery since such repair is performed by stapling a section of polymeric mesh material to the inside of the abdominal wall. The material securing staples must be placed to ensure that a blood vessel is not stapled during the repair.
[0007] The identification of blood vessels during endoscopic surgical operations has been addressed in the prior art. For example, in U.S. Pat. No. 4,770,185 issued to Silverstein et al, an ultrasonic probe is disclosed wherein pulsed ultrasonic energy is used in a catheter to identify both venous and arterial blood flows. A resulting Doppler signal is used to drive a loudspeaker such that the sense of hearing is used in place of the surgeon's sense of feel.
[0008] With the advance represented by HALS procedures there is a need for improved ultrasonic monitoring that can take advantage of the increased freedom created by having a hand inside the body cavity.
[0009] The present invention overcomes the disadvantages of the prior art and provides the surgeon with a cost effective, yet efficiently flexible medical instrument.
SUMMARY OF THE INVENTION
[0010] This need is met by the methods and apparatus of the present invention wherein an ultrasonic sensing system is incorporated into a surgical device attached to a surgeon's hand, and more specifically to a surgeon's fingertip such that the surgical instrument is used to monitor an operational field.
[0011] In one aspect the surgical instrument is useful in minimally invasive surgery where the access to the surgical site is provided by a hand port. The surgical instrument may be manipulated within the surgeon's hand or the instrument may be slidably attached to the surgeon's finger and work as an extension of the surgeon's fingertip.
[0012] In one aspect of the invention, the distal end of the finger device angularly supports the ultrasonic transmitter to aim the ultrasonic transmitter at the operational field and similarly angularly supports the ultrasonic receiver at the operational field.
[0013] In one embodiment, the finger device comprises an ultrasonic transmitter/receiver for assessing the operational field off the pad of the first digit of a finger although an embodiment may be made to accommodate any digit. In the illustrated embodiments, the ultrasonic means operates at a frequency of approximately 20 megahertz. To extend the shelf life and conserve power during usage of battery-operated combinations in accordance with the present invention, power control means are coupled to the circuit means by a pressure switch mounted in conjunction with the ultrasonic means for connecting power to the circuit means only while the finger device is pressed against an operational field to activate. The wires connected to the sensor follow the surgeons arm, exiting the body port and connect to the associated circuitry.
[0014] To enable the ultrasonic sensing systems to be mobile, circuitry for performing ultrasonic sensing is preferably enclosed in housings worn by the surgeon, although off-surgeon configurations are optional. Wiring, run along the surgeon's arm connects the circuitry to transducers formed in or mounted on the distal ends of the hand device. The transducers direct ultrasonic energy to the operational fields defined by the distal ends of the finger device and receive ultrasonic energy reflected from the operational fields. Acoustic lenses, angularly oriented transducer mounts or a combination of the two may direct the transmission and receipt of ultrasonic energy within the operational field.
[0015] In another aspect of the invention signals representative of the tissue or contents of the operational field of a surgical instrument and generated by the ultrasonic sensing system are used to alerting the surgeon. The alert means may take a variety of forms, such as an audible signal generator or a tactile transducer for tactilely signaling the surgeon. The tactile transducer is mounted for access by the surgeon within the finger device. In this way, the present invention extends a surgeon's sense of feel for performance of surgical procedures, particularly HALS procedures. The sensitivity of the ultrasonic sensing system can be adjusted to prevent activation of the alerting means for background signal levels. The level of the alerting signal, whether audible or tactile, can also be adjusted. In one aspect of the invention the alert is a tactile transducer means coupled to the internal surface of the surgical instrument for tactilely communicating to the surgeon's fingertip thereby extending the surgeon's sense of feel. Alternately, the alert may comprise an audible signal generator such as a speaker or earphone.
[0016] In yet a further embodiment, an array of crystals enables imaging of the operational site from the viewpoint of the fingertip.
[0017] In still yet another embodiment, ultrasound energy further allows the modality to be used in treatment of lesions. Solid organs, like the kidney and liver as well as soft tissue like the breast or for that matter, any place where lesions or cellular necrosis identification is desired, are within the teachings of this document.
[0018] It is also understood that the Doppler, ultrasound imaging and ultrasound therapy could be presented in individual or in any modality combinations. The output from the device could also be presented in numerous forms. The imaging and therapeutic applications may be presented on a screen of an ultrasound machine or independent monitor. Typically the monitor would be on the ultrasound machine or room monitor but could work with a smaller screen worn by the user if desired. Ideally the images could be integrated into a transmitter that would remove the cord tethering the finger device.
BRIEF DESCRIPTION OF THE FIGURES
[0019] These and other features, aspects, and advantages of the invention will become more readily apparent with reference to the following detailed description of a presently preferred, but nonetheless illustrative, embodiment when read in conjunction with the accompanying drawings. The drawings referred to herein will be understood as not being drawn to scale, except if specifically noted, the emphasis instead being placed upon illustrating the principles of the invention. In the accompanying drawings:
[0020] [0020]FIG. 1 is a partially sectioned perspective view of a HALS operation using a Doppler ultrasound sensor to monitor blood flow in accordance with the present invention;
[0021] [0021]FIGS. 2 a - c are perspective views of alternate embodiments of a Doppler sensor positioned at the tip of a surgeon's finger;
[0022] [0022]FIG. 3 is a sectioned view of the finger device with an ultrasonic transducer and ultrasonic receiver;
[0023] [0023]FIG. 4 is a perspective view of a finger-mounted ultrasonic sensor electrically connected to a circuit box and strapping means for attaching the circuit box to the surgeon;
[0024] [0024]FIGS. 5 a - c are perspective views of alternate embodiments of an ultrasound imaging sensor with one or more crystals to form an array; and
[0025] [0025]FIG. 6 is a sectioned view of the finger device shown in FIG. 5.
DETAILED DESCRIPTION OF THE INVENTION
[0026] Before explaining the present invention in detail, it should be noted that the invention is not limited in its application or use to the details of construction and arrangement of parts illustrated in the accompanying drawings and description. The illustrative embodiments of the invention may be implemented or incorporated in other embodiments, variations and modifications, and may be practiced or carried out in various ways. Furthermore, unless otherwise indicated, the terms and expressions employed herein have been chosen for the purpose of describing the illustrative embodiments of the present invention for the convenience of the reader and are not for the purpose of limiting the invention.
[0027] Further, it is understood that any one or more of the following-described embodiments, expressions of embodiments, examples, methods, etc. can be combined with any one or more of the other following-described embodiments, expressions of embodiments, examples, methods, etc.
[0028] While the methods and apparatus of the present invention are generally applicable to the performance of these surgical procedures during any operation, they are particularly applicable to their performance during Hand Assisted Laparoscopic Surgery (HALS) and, accordingly, will be described herein with reference to this invention.
[0029] Referring now to FIG. 1, the environment for performing an endoscopic surgical procedure within an abdomen 100 is illustrated. A means for providing hand access, such as a lap disc 110 , for example, model LD111 available from Ethicon Endo-Surgery, Cincinnati, Ohio, is placed into the abdominal wall. A surgeon 120 places his arm 130 and gloved hand 140 through the lap disc 110 and into the abdomen 100 . The index finger 150 (any finger can be used) is capped with a finger device with an ultrasonic sensor 155 . The finger device with ultrasonic sensor 155 is pressed against an operative field 170 . Wires 180 connect to the circuitry box 190 mounted to the surgeon's arm 130 by a strapping means 200 , such as Velcro, elastic, buckle or any conventional fastening means apparent to those skilled in the art.
[0030] In FIG. 2 a Doppler-sensor device approaches a vessel in an operative field 170 to sense its flow characteristics. FIGS. 2 b and 2 c illustrate alternate embodiments of incorporating the ultrasonic transducer of sensor 160 to the side, or finger pad of the fingertip, or as an extension of the fingertip.
[0031] In FIG. 3, an ultrasonic sensor 155 comprises two subcomponents, the ultrasonic transducer 160 and the finger interface element 167 . The ultrasonic transducer 160 comprises an ultrasonic transmitter 210 and an ultrasonic receiver 220 for directing and receiving ultrasonic energy to and from the operative field 170 . The distal most surface of the fingertip sensor 155 supports the ultrasonic transmitter 210 and the ultrasonic receiver 220 . The path of the ultrasonic energy for this embodiment of the invention is represented by the arrowed paths 230 a and 230 b . Acoustic lenses and matching layers may also be utilized with a transmitter and/or a receiver to direct ultrasonic energy to and from the operative field 170 . The acoustic lenses may be made from a number of materials well known in the art to focus the ultrasonic energy as described and shown.
[0032] The fingertip ultrasonic sensor 155 further comprises a finger interface element 167 having an opening 169 for releasably receiving a surgeon's fingertip 168 . Preferably, opening 169 is constructed to compressively engage the surgeon's fingertip 168 . Opening 169 may also have a friction material on its internal surface to provide further gripping capabilities to secure the surgeon's fingertip 168 within opening 169 . Preferably, finger interface element 167 comprises a mounting means, such as a channel 162 for receiving a securing element, such as a strap, to securely fasten the finger interface element 167 to the surgeon's finger 168 .
[0033] For ease of manufacturing, the finger interface element 167 releasably connects with a mounting bracket 165 for mounting the ultrasonic transducer 210 and receiver 220 through conventional snap catches 166 , detents or press fit means. Alternatively, interface element 167 and bracket 165 may be molded as one piece.
[0034] Also shown in FIG. 3 is a pressure switch 250 and tactile transducer 256 . Pressure switch 250 enables completion of the circuit, discussed below. Tactile transducer 256 is located at the distal portion of opening 169 to allow the surgeon to gain an increased sensitivity to the pulsing of any contacted vessels, such as vessel 170 . The tactile transducer 256 may be operated at a frequency of approximately 5 kilohertz.
[0035] [0035]FIG. 4 is a perspective view of the circuit box 190 and strapping element showing the cover 300 offset to reveal structural details of the ultrasonic transducers incorporated therein. Whatever the form of the ultrasonic transducer, an appropriate circuit is provided for activating the transducer to transmit ultrasonic energy to the operational field as directed by the fingertip ultrasound sensor 155 . The circuit also provides for receiving signals generated by the receiver 220 in response to received ultrasonic energy that is reflected from the operational field and for analyzing those signals. Since the circuit is a conventional circuit design as far as transmission and reception of ultrasonic energy and processing of the resulting signals is concerned, it will be described herein only with reference to its assembly and packaging which permits it to be readily combined with the ultrasonic sensor 155 .
[0036] A representative circuit means for activating the transducer is a pressure switch 250 (FIG. 3) that is engaged when the operative field 170 is contacted. The circuitry is packaged on two printed circuit boards 310 , 320 . In general, the circuit boards 310 , 320 are partitioned such that the upper printed circuit board 310 includes the circuitry for driving the ultrasonic transducer and the lower printed circuit board 320 includes the circuitry for receiving signals from the transducer. Accordingly, the upper printed circuit board 310 is connected to the lower circuit board 320 via wiring 330 w and the lower printed circuit board 320 is connected to the ultrasonic receiver via wiring 335 w.
[0037] In the illustrated embodiment, the circuit and transducer are constructed for operation at a frequency of approximately 20 megahertz. While it is apparent that other frequencies can be utilized in accordance with the present invention, the 20-megahertz frequency is used in the illustrated embodiments to better define the focus zone size and depth of penetration of the ultrasonic energy into the tissue. The circuitry on the boards 310 , 320 is of a conventional design. Commercially available components may be surface and otherwise mounted to occupy a limited amount of board space on the boards 310 , 320 . The boards 310 , 320 are also mounted in “piggy-back” fashion, with one board on top of the other to compact the circuitry further and conserve space within the circuitry box 190 . While external circuitry can be utilized in the present invention, the compact arrangement illustrated is preferred since it forms a compact, self-contained enclosure.
[0038] In the illustrated embodiment, the circuitry on the boards 310 , 320 is operated by power from a battery 360 mounted parallel and adjacent to the boards 310 , 320 . The battery 360 can be rechargeable in the event the ultrasonic sensor 155 is manufactured to be reusable. For a rechargeable battery, recharging can take place through the jack 340 . Alternately, power for the circuit can be provided directly through the jack 340 with elimination of the battery 360 .
[0039] More likely is the provision of a disposable device; the battery 360 is selected for power levels available from the battery and its shelf life. Currently, for disposable instruments, alkaline, lithium or silver oxide batteries provide sufficiently high power output and have long shelf life. To be sure that power is not drained from a battery of a battery-powered instrument, a power switch 370 is built into the circuitry box 190 . To verify activation of the ultrasonic sensing system to the surgeon, a light emitting diode 380 or other indicator device located on the circuitry box 190 is activated while power is connected to the ultrasonic sensing system.
[0040] The circuitry on the printed circuit boards 310 , 320 includes two potentiometers 385 , 386 with the potentiometer 386 being accessed through an opening 387 in the board 310 . One of the potentiometers 385 , 386 is used to set the volume of an audible alerting device or the level of signal produced by the tactile transducer while the other one of the potentiometers 385 , 386 is used to set a threshold level to which a Doppler signal is compared via comparator means included within the circuitry on the circuit boards 310 , 320 . If the Doppler signal exceeds the set threshold, then the user of the instrument is alerted either tactilely or audibly during that time. The using surgeon is able to detect venous flow, which generates a continuous alerting signal, and arterial flow, which generates a pulsating alerting signal. Further, a vessel such as the bile duct, which does not contain a fluid flowing at a sufficient velocity to generate a Doppler signal having amplitude in excess of the set threshold, may be determined. While it is contemplated that the potentiometers 385 , 386 will be set and then sealed during production, it is possible to permit field adjustment by disassembly the circuitry box 190 or by providing openings (not shown) through the circuitry box 190 . Resilient plugs or the like can seal such openings, for example.
[0041] If the device is constructed and operable in accordance with the invention of the present application, a surgeon is able to concentrate on manipulating the device into proper positions. After such positioning, the surgeon can sense ultrasonically thereby extending and returning the surgeon's sense of feeling to determine the contents of the instruments' operational fields prior to performing the procedures.
[0042] Alternate alerting means of communicating the Doppler response may comprise a set of headphones, a speaker or the like (not shown) which can be coupled to the circuitry on the boards 310 , 320 by means of an electrical jack, which is mounted in the base of the circuitry box 190 . It is also possible to incorporate a sound source directly into the circuitry box 190 , which would further simplify the structure of the instrument when audible alerting is used.
[0043] Also shown in FIG. 4 is a strapping means 200 that enables the circuit box 190 to be conveniently placed on the surgeons arm. The specific closure means can be accomplished in numerous well-known ways for example Velcro or a buckle. Also well known are alternative mounting means such as belt or pocket clips. If desired, the circuit box 190 could be placed in some location other than on the surgeon.
[0044] [0044]FIG. 5 a is a perspective view of a device showing an ultrasound imaging sensor 155 a with one or more crystals to form an ultrasound transducer array 500 on the distal end of a finger 150 . The imaging sensor device 155 a approaches an operative field 170 to image the tissue's characteristics. A representative ultrasonic transducer array is described in U.S. Pat. No. 6,050,943, and assigned to Guided Therapy Systems, Inc., the contents of which are hereby incorporated herein by reference.
[0045] [0045]FIG. 5 b - c are alternate configurations to incorporate the ultrasonic transducer array into the side or finger pad or a distal extension of the imaging sensor device 155 a.
[0046] [0046]FIG. 6 is a perspective view of a fingertip ultrasound imaging sensor 155 a where like reference numerals have the same description as corresponding numerals of FIG. 3. Ultrasonic transducer array 500 performs both transmitter and receiver functions. The path of the ultrasonic energy for this embodiment of the invention is represented by the arrowed paths 230 a and 230 b . Acoustic lenses and/or matching layers may also be utilized with a transmitter/receiver array to direct ultrasonic energy to and from the operative field 170 to improve imaging quality or therapeutic effect (discussed below). The acoustic lenses can be made from a number of materials well known in the art to focus the ultrasonic energy as described and shown. Accordingly, the acoustic lenses 220 and 230 will not be further described herein.
[0047] Also shown in FIG. 6 is a pressure switch 250 . The pressure switch 250 enables completion of the circuit and image transducer upon contact of the ultrasound imaging sensor 155 a with the operative field 170 .
[0048] [0048]FIGS. 5 and 6 also represent an ultrasound imaging and/or therapy device that would enable the ultrasound energy to be focus to enable a therapeutic effect on the operative field 170 . The therapeutic effect could be the treatment of lesions or solid organs like the kidney and liver as well as soft tissue like the breast or for that matter, any place where lesions or cellular necrosis is desired is within the teachings of this document. The surgeon may first image the tissue by moving the finger or incorporating a mechanism that would move the array while the finger was held in position. After an image is obtained the surgeon may then adjust the power setting of the transducer array 500 to ablate the identified tissue.
[0049] While the methods for performing ultrasonically assisted surgical procedures in accordance with the invention of the present application should be apparent from the foregoing description of illustrative embodiments of the invention, an illustrative method of such performance will now be described for sake of clarity. The method is for operating a device having a distal end for sensing an operational field and a means for activating performance within the operational field. Ultrasonic energy is transmitted to the operational field of the surgical instrument and reflected from the contents of the operational field. The ultrasonic energy reflected from the operational field of the device is received and Doppler signals representative of the contents of the operational field are generated in response to the received ultrasonic energy. The Doppler signals are analyzed to determine the nature of the contents of the operational field of the surgical instrument and the user of the surgical instrument is informed of the contents of the operational field. If the contents of the operational field are confirmed as being appropriate, the surgeon is confident to proceed with the procedure at hand.
[0050] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. In addition, it should be understood that every structure described above has a function and such structure can be referred to as a means for performing that function. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. Accordingly, it is intended that the invention be limited only by the spirit and scope of the appended claims. | Disclosed is a minimally invasive surgical instrument that may be used in hand-assisted laparoscopic surgeries. The device is an ultrasonic transmitter and receiver and may be mounted directed on a surgeon's fingertip and inserted through an incision to allow the surgeon to monitor the operational field during a surgical procedure. The device may be used in combination with tactile feedback or other means of alerting the surgeon of the presence of blood vessels or arteries, for example, to provide the surgeon with an improved tactile sense of the surgical field. | 0 |
BACKGROUND OF THE INVENTION
1. Field of Invention
This invention relates to golf, specifically to an improved practice putting cup that teaches speed as well as direction.
2. Discussion of Prior Art
Numerous gadgets and aids are available for purchase by avid golfers in order to help improve their game. With regard to putting, there are a number of practice cups which may be placed on the golfer's carpet, or the golfer may purchase a piece of carpet or one of a number of specific golf mats simulating a putting green or surface.
Certain deficiencies exist with regard to these available cups. Since these cups of necessity must sit upon a carpet, they require some entry speed for the ball to pass over a ramp or lip. This in itself is not a bad feature since Reference 1 teaches that the ball speed at the front of the cup should be sufficient to roll the ball past the cup approximately 1 to 2 feet in order to optimize a putt's chance of being sunk on a real imperfect green surface. However, the ramps or lips on available cups are not designed for this purpose, see, e.g., Patent Des. 273,126 to Turza, 1984. A simulated putting cup designed to be placed upon rather than into a carpet must be of a type wherein the ball rolls up a ramp and/or over a lip in order to fall into a hole the depth of which can be no more than back down onto the carpet surface. Portable or stand-alone cups on the market are almost all of the ramp type. A distinction between these cups is that they are omnidirectional, i.e., the putt can enter from any direction or they are unidirectional where the putt can only enter from one direction. The latter type can be referred to as planar ramp, “horseshoe” design. Patent Des. 273,126 to Turza, 1984 is typical of a “horseshoe” design. U.S. Pat. No. 5,487,545 to Schindler, 1996 and U.S. Pat. No. 4,906,006 to Sigunick, 1990 are of the omnidirectional type. While putting from any direction may be convenient, this design has serious drawbacks. Since the putt must travel up a conical ramp, any ball which is not putted exactly on the centerline of the hole will be deflected to one side or another as it rolls up the conical shaped ramp (like the sides of a volcano).
U.S. Pat. No. 4,906,006 is unrealistic in several areas. The putting speeds at which putts are holed are incorrect because of the severe ramp angle 22 to 26 degrees and the shallowness of the cup, which is ⅜ inch maximum. Thus the speeds of sinkable putts on actual greens are quite different from the speed and direction of sinkable putts using omnidirectional cups. As opposed to a planar ramp, the conical ramp as also claimed in U.S. Pat. No. 5,487,545 completely deviates from putting on an actual green as it turns putts not exactly on center away from the cup. A flat cup on an actual green does not behave in this manner. Hence, these cups are difficult and frustrating to use as putting training devices. Finally, with these devices as well as with all others on the market, a missed putt provides no feedback with regard to proper speed.
OBJECTS AND ADVANTAGES
My invention adds greatly to the field of putting training devices with regard to teaching correct putting speed. On an actual green there exists an optimum range of putting speeds as discussed in detail by Pelz, Reference 1. Pelz teaches that to overcome imperfections on actual putting greens, a putt must be struck with enough speed to not just reach the hole, but be capable of rolling approximately one to two feet past. Further, if a putt is missed, ideally the putt will stop within two or three feet of the hole. Finally, a firmly struck centered putt will fall into the hole even if its speed could carry the ball as much as six to eight feet past the hole.
This putting cup invention recognizes these ball putting speed (or distance) conditions and accordingly accepts or rejects holing putts. Thus, the cup uniquely teaches correct speed as well as direction.
No cups on the market or putting cup patents have considered or attempted to teach proper putting speeds. For example, five practice putting cups on the market were tested to see how far a centered putt could roll past the location of the center of the hole and still drop, i.e., not bounce over. The worst cup tested let centered balls bounce over the cup which would otherwise travel as little as two feet past. The best cup tested, that which is patented as U.S. Pat. No. 5,487,545, allowed centered balls to drop which would otherwise travel up to four feet past. The results of all the other cups fell between these results. My invention will drop centered putts able to roll up to; eight feet past just as occurs on actual putting greens.
The present invention will:
Reject putts that are not struck firmly enough to be capable of rolling one to two feet past the hole. Capture putts behind the hole (those which miss to the left or right) which would be capable of rolling only two to three feet past the hole. Faster putts would roll over the capture means. Allow very firm, centered putts to drop into the hole rather than bounce over. These are putts which would fall into the hole on actual greens and would be capable of rolling some six to eight feet past the hole.
SUMMARY
The present invention is a practice putting cup which teaches a golfer correct putting speed as well as direction. Optimum speed is that firmness of the struck putt which would roll a ball one to two feet past the hole. The invention rejects putts which are not sufficiently firm, i.e., would roll less than one foot past and captures, behind the hole, missed putts which would travel up to three feet past the hole. Additionally, a firmly struck centered putt will drop into the hole for speeds which would carry the ball as much as six to eight feet past the hole as would occur on an actual putting green. The invention discriminates these speeds by a planar ramp design in front of the hole, by a trough of specific size behind the hole, and by the actual depth of the hole. The invention has a ramp and surface width sufficient to allow putts missed left and right of the hole by a significant margin to still provide feedback with regard to proper speed.
DRAWING FIGURES
FIG. 1 is an isometric sketch of the putting cup invention which presents an overall view and identifies the various components thereof.
REFERENCE NUMBERS IN DRAWINGS
4
Ball entry ramp
5
Hole surface
6
Hole (USGA regulation size)
7
Front edge (of ball entry ramp)
8
Ball retention trough
9
Rear retainer
10
Side wall(s) of cup
11
Golf ball
DETAILED DESCRIPTION
Preferred Embodiment FIG. 1
The preferred embodiment of the putting cup is shown in FIG. 1 . The putting cupis rectangular in planform approximately two regulation golf hole diameters in width by three and one half diameters in length. It has a planar “ball entry ramp” 4 of approximately 10 degrees slope by three quarters of a golf ball diameter in height with a “front edge” 7 radius of less than one thirtieth of a golf ball diameter. With the putting cup placed upon a carpet or actual putting green of average speed, Stimpmeter reading 9 to 10 , a ball putted with optimum speed and direction will roll longitudinally up the center of ramp 4 onto adjoining “hole surface” 5 and drop into regulation size “hole” 6 . Hole surface 5 is also approximately three quarters of a golf ball diameter in height and hole 6 is greater than one half golf ball diameter in depth. If the hole surface were not flat but rather a continuation of the ramp, putted balls which miss to the left or right of the hole can roll back down the ramp. Optimum speed putts then could not be correctly delineated. Optimum speed means that if the putting cup were not present the ball would roll one to two feet past the position of the rear of the hole. A golf ball putted left or right of hole 6 within one half a hole diameter of the edge of the hole will roll into “trough” 8 . The trough is approximately three quarters of a ball diameter front to back. The ball will either be stopped by “rear retainer” 9 which is approximately one fourth of a ball diameter in height and stay in the trough or the ball will hop over if its speed would roll it more than three feet past the hole were the putting cup not present. Missed puts which contact the inside of “side wall(s)” 10 will be directed into trough 8 thus increasing the width of missed putts for which putting speed feedback is provided.
The putting cup can be constructed of wood with or without a softer fabric surface or it can be one-piece molded of a suitably resilient plastic or rubber material.
Operation of Invention FIG. 1
The putting cup FIG. 1 is designed to teach putting speed as well as the normal use of practice putting cups which is to teach direction. In the game of golf, putting speed is discussed, but it is always described in terms of how far a golf ball rolls with respect to the hole. Speed and distance are related on a flat surface through the energy balance equation:
½mv 2 =μmgS
where
m ball mass v ball speed μ coefficient of rolling friction g gravitational constant S distance
This equation states that the kinetic energy of the ball is dissipated due to frictional effects as the ball rolls distance S.
The invention is designed to recognize three critical speeds and discriminate accordingly. These speeds equated and presented as distances the ball could roll past the hole are as follows:
S o optimum distance, one to two feet; based upon the results of Pelz, Reference 1 S t tap-in distance, two to three feet; maximum distance one would want a missed putt to travel in order to have a very strong chance of sinking the next putt S m make-able distance, six to eight feet; maximum distance a centered putt could otherwise travel and still drop into the hole, see again Reference 1.
These distances were equated to velocities using the above equation and a coefficient of rolling friction measured on a selected carpet with performance equal to a putting green of average speed, that is a “green speed” Stimpmeter reading of 9-10. Stimpmeter reading is the accepted method for quantitatively defining “green speed”. Green speed is relatively how fast a golf ball rolls on an actual green, see again Reference 1.
The front edge 7 radius and ball entry ramp 4 slope and height were designed to recognize S o . If the ball speed is below that which equates to S o the ball will not make it up to the top of the ramp and will roll backwards back down. A ball putted at a speed which does not equate to at least S o can not drop into the hole. A specific minimum and optimum firmness of putt is then taught.
Every practice putting cup on the market which was tested failed to meet this firmness of putt requirement. They all allowed more weakly struck putts to be holed.
With every practice cup on the market if the putt is missed to the left or right nothing more can be taught other than that the direction was incorrect. With the present invention if the putt is missed its second critical distance, S t is recognized by ball retention trough 8 and rear retainer 9 . If the missed putt ball speed is greater than that to satisfy S o but less than that to satisfy S t the ball will roll into trough 8 and be held by rear retainer 9 . If the speed is greater the ball will hop over retainer 9 .
Entry ramp 4 and hole surface 5 are sufficiently wide, two hole diameters, to accommodate a wide range of missed putts. The raised side walls 10 of the invention further extend the range of missed putts which can be measured for speed.
If a golf ball is putted quite firmly on an actual green, measurements show that if the putt is on center with the hole, the ball, can drop into the hole even if it could otherwise roll as much as six to eight feet past.
As a golf ball travels in free space between the front and back edges of a hole the ball free-falls due to gravity. If the speed is not excessive the ball will have time to free-fall more than one half a ball diameter such that the center of mass of the ball will be below the height of the back of the hole when the ball strikes the back lip. In theory then, this ball stands a good chance of rebounding off the inside surface at the back of the hole and dropping into the hole. If, however, the depth of the hole in a practice cup is less than one half a ball diameter, the free-falling ball will simply hit the surface at the shallow bottom of the hole and can therefore unrealistically bounce up and hop over the back of the hole. It might seem evident that a practice putting cup should be deep enough to simulate a hole on an actual green. Yet, every practice cup on the market that has been designed to be: placed upon a putting surface fails to recognize this important aspect. They are all too shallow. The present invention has a hole depth greater than a half ball diameter and hence is the only one which allows very firm putts to drop into the hole as would occur on actual putting greens.
CONCLUSIONS, RAMIFICATIONS, AND SCOPE
Thus, the reader will see that my practice putting cup invention provides a training aid to serious golfers which goes far beyond anything presently available. By teaching proper putting speed as well as direction, the invention will contribute significantly to improving a golfer's putting skills.
While my above description contains many specificities, those should not be misconstrued as limitations of the scope of my invention, but rather as an exemplification of one preferred embodiment thereof.
Other variations are possible. For example, the invention has a flat bottom, not shown, for use on any suitable putting surface, carpet, or actual putting green. It could be provided with small cleats or projections at the four corners of the bottom to prevent movement when the back of the hole is firmly struck with a golf ball. The invention for cost consideration will most probably be molded from a suitable resilient plastic, but an additional more expensive version could be of a fine wood such as maple, oaks or walnut with a quality green felt surface such that the cup can be presented as a gift, prize, or golf trophy for example for a “hole-in-one” trophy. A trophy that had an actual use certainly would be unusual. Additionally, if the golfer's use was predominantly to learn speed as opposed to direction the invention could be supplied with a plug to fill the hole. This would allow the full width to be used solely for speed or distance training.
Another, version of the invention would be the inclusion of a practice putting carpet or mat on which to place the putting cup. The size for this carpet, based upon extensive testing, would be approximately 20 inches in width by 10 to 12 feet in length. The carpet would be provided with a predetermined Stimpmeter performance, for example 8, 10, or 12. This would enable the serious golfer to experience known, exact putting conditions for practice in his home which would duplicate the green speed conditions of actual course greens that the golfer is accustomed to playing.
Accordingly, the scope of the invention should be determined not by the embodiment illustrated, but rather by the appended claims and their legal equivalents. | A practice putting cup which teaches a golfer correct putting speed as well as correct putting direction. To overcome imperfections on actual putting greens it is recognized that a putt must be struck with enough speed to not just reach the hole, but be capable of rolling approximately one to two feet past the hole. Further, if a putt is missed, ideally the putt will stop within two to three feet of the hole. Finally, a firmly struck centered putt will fall into the hole even if its speed could carry the ball as much as six to eight feet past the hole. This putting cup recognizes these ball putting speed (or distance) conditions and accordingly accepts or rejects holing putts. Thus the cup uniquely teaches correct speed as well as direction. | 0 |
BACKGROUND OF THE INVENTION
1. Technical Field Pertinent to the Invention
The present invention relates to a tillering promoter for a plant comprising, as the effective ingredient(s), an amino acid, especially at least one of arginine, glutamine and proline which is effective for increasing tillering (as well known, branching out from the joints of stems near to the roots of rice, barley and wheat, lawn grass or the like) and weight of living plant, or inosine in addition to the amino(s) acid, and to the use of such a tillering promoter for a plant, or it relates to a method for tillering promotion of a plant wherein the amino acid(s) and inosine are each applied to the same part(s) or different part(s) of the plant at the same time or at slightly different times (i.e., used in combination).
2. Related Art
The present inventors have previously developed a withering preventing and quick-acting nutrition supplementing agent for a gramineous plant comprising proline, one kind of amino acid, or inosine in addition thereto, as the effective ingredient(s) (Japanese Patent Application No. 308,281/1999). As a result of the studies for finding out further novel effects, the present inventors have achieved the present invention.
Hitherto, some examples have been known wherein an amino acid-related compound, e.g., proline is applied to a plant.
For example, (a) Japanese Patent Publication No. 42,566/1971 discloses a promoter of flower bud formation comprising at least one of uracil and cytosine, and proline.
However, since the increase of the number of tillering is not observed in the promoter of flower bud formation and the method of application is different from the case of the present invention, the promoter is obviously different from the present invention.
Furthermore, for the promotion of the tillering of lawn grass, there are known some examples wherein substances having indole skeleton(s) or plant hormone(s).
For example, (a) Japanese Patent Application Laid-open No. 267,803/1995 discloses a tillering promoter for a gramineous plant comprising an fluorine-containing indolebutyric acid derivative, e.g., an alkyl ester of 4,4,4-trifluoro-3-(indole-3-)butyric acid.
However, the tillering promoter is a chemical fertilizer and thus, it is obviously different from the present invention wherein amino acids, i.e., natural products are utilized, in view of the influence against the environment.
Moreover, (b) Japanese Patent Application Laid-Open No. 82,113/1995 discloses a growth promoter of lawn grass comprising a gibberellin and a cytokine.
However, the growth promoter for lawn grass comprises plant hormones of gibberellin and cytokine, and thus, there is a possibility of exerting undesirable influences on the natural environment, so that the promoter is obviously different from the present invention.
Furthermore, (c) Japanese Patent Application Laid-Open No. 201,914/1991 discloses a method for the promotion of the rooting and tillering of rice seedlings for transplantation, which comprises applying an amino acid fermentation liquid (containing, for example, proline, alanine, valine, and glutamic acid all together) during raising of seedlings in wet-rice farming.
However, in the method of tillering promotion, proline is not solely used, and the amount of the amino acid fermentation liquid to be used is defined as total concentration of the amino acids, so that these amino acids are placed on the same level, i.e., are treated as equivalents.
Incidentally, for example, lawns are utilized in many places such as parks, gardens and ball game fields, and are particularly indispensable for golf courses. However, a large quantity of fertilizers and pesticides has hitherto been used for maintenance of lawn grass and the use has become a big problem in view of the environmental aspect.
In particular, the stress by high temperature causes cold-district type lawn grass indirect growth stop and direct withering, but there is only a measure of good air-ventilation against the problems.
SUMMARY OF THE INVENTION
[Problems to be Solved by the Invention]
Thus, it is an object of the present invention to provide a tillering promoter for a plant which enables the reduction of the amount of fertilizer hitherto used in a large amount and the maintenance of a satisfactory green state by promoting the tillering of a plant, especially lawn grass without requiring the application of pesticides and plant hormones, also exhibits growth promotion and coloring promotion of leaves, is not a chemical fertilizer, and does not adversely affect the environment and men and beasts. Another object is to provide a method for applying the same.
[Means for Solving the Problems]
As a result of extensive studies for achieving the aforementioned objects, the present inventors have first found that an amino acid, especially proline exhibits a remarkable effect on the promotion of the tillering of lawn grass and inosine has an action of enhancing the tillering effect of the amino acid by promoting the growth of a plant. Accordingly, they have accomplished the present invention based on the findings.
Namely, the present invention relates to a tillering promoter for a plant comprising an amino acid, especially proline, or inosine in addition thereto, as effective ingredient(s), and a method for tillering promotion for a plant wherein the tillering promoter is especially applied onto the leaf surfaces.
DETAILED DESCRIPTION OF THE INVENTION
The following will explain the present invention in detail.
The target plants to which the tillering promoter of the present invention is to be applied include preferably lawn grass, but also rice, fruits vegetables, leafy vegetables, decorative plants, and the like.
As the amino acids, there may be mentioned arginine, glutamine and proline, and especially proline is effective, but these amino acids are not necessarily to be a purified one. They may be in the form of a protein hydrolysate or a mixture of amino acids containing a large quantity of proline unless it exerts an adverse effect. Each amino acid is preferably a product having a high purity of 90% or more (ratio of the amino acid per the total solute excluding the inosine in the tillering promoter for a plant of the present invention to be applied onto leaf surfaces).
The tillering promoter for a plant of the present invention comprising an amino acid, especially proline, as the effective ingredient can be prepared into a form wherein the effective ingredient is dissolved optionally in an appropriate solvent such as water or the like. Moreover, the promoter can be formulated into a powder, granules, or tablets by using an optional filler or binder. The application method is preferably foliar application. In this case, an amino acid concentration of 0.2 ppm to 0.2% (2,000 ppm), preferably 10 to 300 ppm, further preferably 100 to 300 ppm is effective. This is because no effect is exhibited at a concentration lower than the range, and there is a possibility of withering by excessive fertilization at a concentration higher than the range. By the way, in the case of dissolving in a solvent, it is optional to formulate the promoter by incorporating a fungicide, a surfactant, or a preservative in view of the prevention of rot. Furthermore, in the case of foliar application, the ombined use with a spreader is effective.
As the way of application of the tillering promoter including application timing, there may be mentioned application as an additional fertilizer, application after mowing grass, or the like. With regard to the way of fertilizing, it is particularly effective to apply amino acid(s), especially proline, to the above-ground part(s) such as foliar application or the like, and inosine to subterranean part(s) by spraying to soil, addition to hydroponic medium, or the like.
The foliar application of proline is effective not only for tillering promotion of a plant but also as a means for promoting the growth such as prevention of withering, feeding of fast-acting nitrogen, and the like. Moreover, the promotion of coloring leaves is also observed.
Application amounts of the tillering promoter for a plant of the present invention vary depending on the application timing, the kind of plants, cultivation density, growing stage, and so on. In short, the amounts may be ones in which the tillering of the plant cultivated by using the tillering promoter of the present invention are superior to the tillering of the plant cultivated under entirely the same conditions with the exception that the tillering promoter of the present invention is not applied. It is possible to determine the amounts by some preliminary comparative test which is easy to carry out for those skilled in the art. For example, in the case of foliar application in a liquid form (as an agent for foliar application), proline may be applied at a low concentration, e.g., as low as 0.2 ppm within the above concentration range. That is, the tillering promotion of lawn grass is effected at such a low concentration. In addition, the application amounts of inosine may be in a range of 0.05 to 1 ppm to soil (5 to 100 g per 100 tons of soil), and in the case of hydroponic cultivation, inosine may be applied in an amount of 0.1 to 2 ppm to hydroponic medium.
By the way, the tillering promoter for a plant of the present invention may be in a form containing also (mixing) inosine in addition to a predetermined amino acid as explained in the above. However, the amino acid and inosine may be, of course, applied each at the same time or at slightly different times. Such an application way is also an embodiment of the present invention. As a formulation suitable for such an application way, there may be mentioned a kit form wherein the amino acid and inosine are packaged separately and both the packages are made one set.
EXAMPLES
In the following will be explained the present invention in further detail with reference to the Examples.
Example 1
Effect of Proline on Hydroponic Cultivation of Lawn Grass (1)
Seedlings of grass (a European grass; bent grass) were raised and divided into four groups of A to D, and hydroponic cultivation was carried out (Table 1 shown below). Concerning Groups B and D, inosine was added to each hydroponic medium in such amount that the concentration became 2 ppm. Concerning Groups C and D, proline was applied onto leaf surfaces once a week in an amount of 20 ppm. Group A was the control. Upon confirmation on the 40th day, the tillering promotion was clearly observed in the two groups of C and D wherein proline had been applied onto leaf surfaces, but no tillering promotion was observed in Groups A and B which had not been applied. Furthermore, five average stocks which had not been withered were sampled from each group and examined. As shown in the following Table 1, with regard to all of the root length, leaf length and number (above-ground parts), total weight of the living plant, and tillering number, good growth was found in the proline-treated plots. Especially, it was confirmed that the effect became more remarkable when inosine was used in combination.
TABLE 1
Comparison of the lawn grasses
between the groups (5 roots each)
Average
Average
Total weight
Number of
root
leaf
Number of
of living
tillering
length
length
leaves per
plants per
per one
(cm)
(cm)
one root
five roots (g)
root
A (Control)
1
18
5
0.28
1
B (Inosine)
2
20
7
0.40
2
C (Proline)
1
22
16
0.53
5
D (Inosine +
3
22
23
1.00
6
Proline)
Example 2
Effects of Proline, Glutamine, Arginine and Urea on Hydroponic Cultivation of Grass
Seedlings of grass (a European grass: bent grass) were raised and divided into five groups of A to E, and hydroponic cultivation was carried out (Table 2 shown below). Group A was the control. Concerning Group B, proline was applied onto leaf surfaces once a week in an amount of 20 ppm. And, concerning the three groups of C to E, aqueous solutions of arginine, glutamine, and urea were applied onto leaf surfaces, respectively, once a week in such a amount that the nitrogen amount was the same as that of the proline in Group B. Upon confirmation on the 40th day, the tillering promotion was clearly observed in the groups of B to D, but no tillering promotion was observed in the groups of A and E.
Furthermore, five average stocks which had not been withered were sampled from each group and examined. As shown in the following Table 2, with regard to the number of leaves and total weight of the living plant, good results were observed in the plots treated with proline, glutamine, and arginine, and the effects were more remarkable than that of urea which is a generally-used nitrogen source for foliar application.
TABLE 2
Comparison of the lawn grasses
between the groups (5 roots each)
Average
Average
Total weight
Number of
root
leaf
Number of
of living
tillering
length
length
leaves per
plants per
per one
(cm)
(cm)
one root
five roots (g)
root
A (Control)
2
14
8
0.33
2
B (Proline)
2
14
17
0.60
5
C (Arginine)
2
18
9
0.51
3
D (Glutamine)
2
18
11
0.66
3
E (Urea)
2
15
6
0.34
1
Example 3
Effect of Proline on Hydroponic Cultivation of Grass (2)
Seedlings of grass (a European grass: bent grass) were raised and divided into six groups of A to F, and hydroponic cultivation was carried out (Table 3 shown below). At that time, inosine was added to the hydroponic media for all the groups in such amount that the concentration became 2 ppm in each hydroponic medium. Group A was the control. In the groups of B to F, proline was applied onto leaf surfaces once a week with the concentration being changed stepwise. Upon confirmation on the 40th day, the tillering promotion was clearly observed in the groups of B to F, but no tillering promotion was observed in Group A. However, inhibition of the growth or withering was observed in Group F.
Furthermore, five average stocks which had not been withered were sampled from each group and examined. As shown in the following Table 3, with regard to the number of leaves and total weight of the living plant, good results were observed in the plots treated with proline at a concentration of 2 ppm to 0.2%.
TABLE 3 Comparison of the lawn grasses between the groups (5 roots each) Average Average Total weight Number of root leaf Number of of living tillering length length leaves per plants per per one (cm) (cm) one root five roots (g) root A (Control) 3 22 14 0.59 2 B (2 ppm 4 24 14 1.04 3 Inosine) C (20 ppm 4 24 15 0.95 4 Proline) D (200 ppm 5 24 24 1.01 4 Proline) E (0.2% 5 23 14 0.90 3 Proline) F (2.0% 3 19 11 0.40 3 Proline)
[Effects of the Invention]
According to the present invention, the application of at least one of proline, arginine and glutamine, or the application of inosine in addition to the amino acid(s) promotes the tillering of a plant, especially lawn grass, and also affords a nutrition effect easily. | Herein are disclosed a tillering promoter for a plant comprising an amino acid, especially proline, or inosine in addition thereto, as effective ingredient(s), and a method for tillering promotion for a plant wherein the tillering promoter is especially applied onto the leaf surfaces, in accordance with which are provided a tillering promoter for a plant which enables the reduction of the amount of fertilizer hitherto used in a large amount and the maintenance of a satisfactory green state by promoting the tillering of a plant, especially lawn grass without requiring the application of pesticides and plant hormones, also exhibits growth promotion and coloring promotion of leaves, is not a chemical fertilizer, and does not adversely affect the environment and men and beasts, and a method for applying the same. | 0 |
CROSS-REFERENCE TO RELATED APPLICATION
This application is the U.S. national phase of PCT Appln. No. PCT/EP2009/053415 filed Mar. 24, 2009 which claims priority to German application DE 10 2008 000 931.8 filed Apr. 2, 2008.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to wax-like β-ketocarbonyl-functional organosilicon compounds, and to a process for their preparation.
2. Description of the Related Art
The standard preparation of silicone waxes is by hydrosilylation of hydrogensiloxane and alpha-olefins. The linear polymer thusly obtained consists predominantly of alkylmethylsiloxane units. On account of the required minimum chain length of the alkyl radicals, their fraction of the overall mass is very high, in most cases >70%, meaning that the silicone character is less marked. Moreover, the standard process has the inherent disadvantage of a hydrosilylation with residual content of SiH groups and the heavy metal content of the wax in the form of platinum compounds, which are required as catalysts.
DE 102 96 506 T5 describes linear silicone waxes which comprise at least 25 mol% of RR 1 SiO units, in which R is a C 1 -C 8 -alkyl radical or C 6 -C 10 -aryl radical, and R 1 corresponds to a long-chain organic radical having at least 16 carbon atoms and which may contain 1 to 10 heteroatoms. These waxes comprise a high percentage of long-chain organic radicals in the lateral position of the siloxane chain. Compared with siloxanes with a high fraction of dimethylsiloxane units, such polymers are complex and expensive to produce.
EP 1 624 010 A1 likewise describes linear silicone waxes which, apart from C 1 -C 20 -substituents, also contain substituents which consist of at least one behenic ester group bonded to the siloxane chain via a pentaerythritol radical. Although the molar amount can vary over a wide range, considerable expenditure is associated just with producing this large substituent. Finally, the aliphatically unsaturated behenic ester is bonded to the siloxane via hydrosilylation, as a result of which the silicone wax again contains heavy metal from platinum catalyst. Since the reaction components are not very soluble in one another, relatively large amounts of solvent are required to carry out the hydrosilylation. One production variant is based on the esterification of a behenic ester carbinol with anhydridosiloxane. In this variant, although no additional heavy metal compound is required, it is not possible to also dispense with solvents.
In a similar manner, according to US 2003/096919 A1, silicone waxes are prepared from an SiH—, SH— or amino-functional siloxane and a fatty acid or fatty alcohol component which additionally also contains an aliphatic double bond. A preferred fatty component is a behenic compound. The linear siloxanes are typically short-chain, and the organic fraction of the wax products is therefore in most cases considerably more than 50% by weight, as a result of which the siloxane character is not very marked.
WO 2007/060113 A2 describes a process for the preparation of β-ketocarbonyl-functional organosilicon compounds, in which diketenes are reacted with organosilicon compounds having amino groups. Here, oils are obtained.
SUMMARY OF THE INVENTION
It was an object to provide organosilicon compounds which are waxes but comprise only a small fraction of relatively long-chain alkyl radicals, and in which the silicone character is retained. A further object was to provide organosilicon compounds which are free from platinum compounds and residual amounts of SiH groups, with which no high-risk hydrogen evolution is possible. A still further object was to provide a process for the preparation of these organosilicon compounds which is simple and cost-effective and which proceeds spontaneously without a catalyst. These and other objects are achieved by the invention, where long chain-substituted β-ketocarbonyl groups are bonded to organosilicon compounds bearing a reactive hydrogen attached to —O—, —NH—, —NR 2 —, or —S—.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The invention thus provides wax-like β-ketocarbonyl-functional organosilicon compounds which comprise at least one Si-bonded radical B of the general formula
[R 3 CH 2 —C(═O)—CHR 3 —C(═O)—X-] y L-(Si) (I),
where
R 3 is a monovalent, optionally substituted hydrocarbon radical having at least 12 carbon atoms, preferably having at least 14 carbon atoms, X is a radical of the formula —O—, —NH—, —NR 2 — or —S—, preferably —NH—, where R 2 is a monovalent hydrocarbon radical having 1 to 18 carbon atoms, which may contain one or more separate nitrogen atoms, L is a (y+1)-functional organic radical, preferably a divalent hydrocarbon radical having 1 to 18 carbon atoms, y is 1, 2 or 3, preferably 1, and (Si)— is the bond to the Si atom,
with the proviso that R 3 is present in an amount of at most 30% by weight, preferably at most 25% by weight, more preferably at most 20% by weight, yet more preferably at most 15% by weight, and in particular at most 10% by weight, in each case based on the total weight of the organosilicon compounds.
The invention further provides a process for the preparation of the wax-like β-ketocarbonyl-functional organosilicon compounds, in which organosilicon compounds (1) having at least one radical A of the general formula
[HX-] y L-(Si) (II)
are reacted with diketenes (2) of the general formula
where R 3 , L, X, y and (Si)— have the meaning given therefor above.
Organosilicon compounds (1) which can be used include silanes and oligomeric or polymeric organosiloxanes. They preferably contain 1 to 2000 Si atoms, more preferably 2 to 1000 Si atoms and most preferably 20 to 700 Si atoms.
Preferably, the organosilicon compounds (1) are organopolysiloxanes containing units of the general formula
A a R b ( OR 1 ) c SiO 4 - ( a + b + c ) 2 , ( IV )
where
A is a radical of the formula (II), R is a monovalent, optionally substituted hydrocarbon radical having 1 to 18 carbon atoms per radical, R 1 is a hydrogen atom or an alkyl radical having 1 to 8 carbon atoms, a is 0 or 1, b is 0, 1, 2 or 3 and c is 0 or 1,
with the proviso that the sum a+b+c is less than or equal to 3 and on average at least one radical A is present per molecule.
Preferred examples of organosilicon compounds (1) are organopolysiloxanes of the general formula
A g R 3-g SiO(SiR 2 O) 1 (SiRAO) k SiR 3-g A g (V),
where
A is a radical of the formula (II), g is 0 or 1, preferably 1, l is 0 or an integer from 1 to 2000 and k is 0 or an integer from 1 to 20, preferably 0,
with the proviso that on average at least one radical A is present per molecule.
The organosilicon compounds (1) used in the process according to the invention preferably have a viscosity of from 1 to 1,000,000 mPa·s at 25° C., more preferably 100 to 50,000 mPa·s at 25° C.
Examples of radicals R are alkyl radicals such as the methyl, ethyl, n-propyl, isopropyl, 1-n-butyl, 2-n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neo-pentyl, and tert-pentyl radicals, hexyl radicals such as the n-hexyl radical, heptyl radicals such as the n-heptyl radical, octyl radicals such as the n-octyl radical and isooctyl radicals such as the 2,2,4-trimethylpentyl radical, nonyl radicals such as the n-nonyl radical, decyl radicals such as the n-decyl radical, dodecyl radicals such as the n-dodecyl radical, and octadecyl radicals such as the n-octa-decyl radical; cycloalkyl radicals such as the cyclo-pentyl, cyclohexyl, cycloheptyl and methylcyclohexyl radicals; alkenyl radicals such as the vinyl, 5-hexenyl, cyclohexenyl, 1-propenyl, allyl, 3-butenyl and 4-pentenyl radicals; alkynyl radicals such as the ethynyl, propargyl and 1-propynyl radicals; aryl radicals such as the phenyl, naphthyl, anthryl and phenanthryl radicals; alkaryl radicals such as the o-, m-, p-tolyl radicals, xylyl radicals and ethylphenyl radicals; and aralkyl radicals such as the benzyl radical and the α- and the β-phenylethyl radicals.
Examples of hydrocarbon radicals R also apply to hydrocarbon radicals R 2 .
Further examples of R 2 are N-containing radicals such as
—CH 2 CH 2 NH 2 , —CH 2 CH 2 NHCH 3 , —CH 2 CH 2 N(CH 3 ) 2 , —CH 2 CH 2 CH 2 NH 2 , and —CH 2 CH 2 CH 2 N(CH 3 ) 2 .
Preferably, the radical R 3 has at most 18 carbon atoms, more preferably 14 to 16 carbon atoms. Radical R 3 is most preferably a C 14 -C 16 -alkyl radical.
Examples of radicals R 3 are the dodecyl, tetradecyl, hexadecyl and octadecyl radicals.
Examples of radicals L are
—CH 2 CH 2 —, —CH(CH 3 )—, —CH 2 CH 2 CH 2 —, —CH 2 C(CH 3 )H—, —CH 2 CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH(CH 3 )—, and —CH 2 CH 2 CH 2 NHCH 2 CH 2 —, —CH 2 CH 2 CH(CH 3 )NHCH 2 CH 2 —, where the —CH 2 CH 2 CH 2 — radical is preferred.
Examples of radicals A are
—CH 2 CH 2 CH 2 OH, —CH 2 OCH 2 CHOH, —CH 2 CH 2 CH 2 SH, —CH 2 CH 2 CH 2 NH 2 . —CH 2 CH 2 CH 2 NHCH 3 , —CH 2 CH(CH 3 )NH 2 . —CH 2 CH 2 CH(CH 3 )NH 2 and —CH 2 CH 2 CH 2 NHCH 2 CH 2 NH 2 .
Organosilicon compounds (1) which contain primary amino groups are preferably reacted by the process described in WO 2007/060113 A2, in particular page 2, line 1 to page 3, line 1 and page 6, line 30 to page 9, line 8, incorporated herein by reference.
Preferably, therefore, organosilicon compounds (1) which contain primary amino groups as radical A are reacted with diketenes (2) in the presence of organic compounds (3) which delay or prevent the reaction of primary amino groups with β-ketocarbonyl compounds. Examples of such compounds (3) are aldehydes and ketones. Preferred examples are acetone, butanone, methyl isobutyl ketone and cyclohexanone. Preferably, the organosilicon compound (1) is firstly mixed with the organic compound (3) and then the diketene (2) is added.
Preferably, in a first stage, organosilicon compounds (1) are reacted with organic compounds (3), where the compounds (3) form protective groups on the amino groups in the radical A of the formula (II), and then, in a second stage, the organosilicon compounds (1) having the protected amino groups obtained in the first stage (reaction products of (1) and (3)) are reacted with diketenes (2). In the reaction with diketene, the protective group surprisingly cleaves off again from the amino group in the radical A of the formula (II).
If the organosilicon compounds (1) comprise only secondary amino groups in the radical A of the formula (II), they can be reacted directly with diketenes (2). If X is —O— in the radical A of the formula (II), tertiary amine bases are preferably used as catalysts, their concentration preferably being 50 to 1000 ppm by weight.
In the process according to the invention, diketene (2) is preferably used in amounts of 0.5 to 1.5 mol, preferably 0.7 to 1.2 mol, per mol of HX group in the radical A of the formula (II) of the organosilicon compound (1).
The diketenes (2) are solid substances at room temperature, meaning that their reaction with compounds (1) preferably takes place at elevated temperature, preferably at 50 to 100° C., so that the diketenes (2) are present in the molten state. Alternatively, it is also possible to use solvents, although this procedure is not preferred.
Preferably, the process according to the invention is carried out under the pressure of the ambient atmosphere, thus about at 1020 hPa. However, it can also be carried out at higher or lower pressures.
Wax-like β-ketocarbonyl-functional organosilicon compounds which can be obtained are silanes, oligomeric or polymeric organosiloxanes. They preferably contain 1 to 2000 Si atoms, more preferably 2 to 1000 Si atoms and most 20 to 700 Si atoms.
Preferably, the wax-like β-ketocarbonyl-functional organosilicon compounds obtained are organopoly-siloxanes consisting of units of the general formula
B d R e ( OR 1 ) f SiO 4 - ( d + e + f ) 2 , ( VI )
where
B is a radical of the formula (I), R is a monovalent, optionally substituted hydrocarbon radical having 1 to 18 carbon atoms per radical, R 1 is a hydrogen atom or an alkyl radical having 1 to 8 carbon atoms, d is 0 or 1, e is 0, 1, 2 or 3 and f is 0 or 1,
with the proviso that the sum d+e+f is less than or equal to 3 and on average at least one radical B is present per molecule.
Preferred examples of wax-like β-ketocarbonyl-functional organosilicon compounds are organopolysiloxanes of the general formula
B z R 3-z SiO(SiR 2 O) m (SiRBO) n SiR 3-z B z (VII),
where
B is a radical of the formula (I), z is 0 or 1, preferably 1, m is 0 or an integer from 1 to 2000 and n is 0 or an integer from 1 to 20, preferably 0,
with the proviso that on average at least one radical B is present per molecule.
In the β-ketocarbonyl-functional organopolysiloxanes according to the invention, R 3 is preferably present in an amount of at least 2% by weight.
The β-ketocarbonyl-functional organopolysiloxanes according to the invention have the advantage that, even with a low content of relatively long-chain alkyl chains, they are waxes and the silicone character is nevertheless retained.
This gives rise to the advantage that linear siloxanes with alkyl-β-ketoamide groups at the chain end even up to a polydimethylsiloxane fraction of more than 95% by weight still have wax-like solids consistency. Depending on the chain length of the siloxane, these waxes have a rather soft to very brittle character and can be produced easily and safely from the α,ω-amino-propyldimethylsiloxanes and standard commercial alkyl ketene dimer.
The melting range of the resulting β-ketocarbonyl-functional organosilicon compounds according to the invention is ca. 40-60° C., depending on the size of R 3 . According to the preparation process, the waxes according to the invention are free from heavy metal and also free from SiH radicals and they have marked silicone character. They exhibit good solubility in liquid organopolysiloxanes, such as silicone oils, in contrast to the highly alkylated standard waxes.
The silicone waxes according to the invention have the advantage that with them a “gelling” of preferably volatile, linear or cyclic siloxanes is achieved. This is used in particular in cosmetics. The silicone waxes according to the invention are dissolved at elevated temperature in volatile linear or cyclic siloxanes. Upon cooling, creamy wax formulations, which are preferably soft and of firm consistency and which preferably consist to a large part of the volatile or thin-liquid linear or cyclic siloxanes, are obtained.
The invention therefore provides creamy wax formulations comprising
(a) wax-like β-ketocarbonyl-functional organosilicon compounds according to the invention and (b) linear, branched or cyclic organosilicon compounds with a viscosity of 0.65 to 100,000 mPa·s at 25° C., preferably 0.65 to 500 mPa·s at 25° C.
Preferred (b) linear or cyclic organosilicon compounds are linear or cyclic organopolysiloxanes, such as hexamethylcyclotrisiloxane (D 3 ), octamethylcyclotetra-siloxane (D 4 ), decamethylcyclopentasiloxane (D 5 ), hexa-methyldisiloxane, octamethyltrisiloxane, decamethyl-tetrasiloxane or else relatively long polydimethyl-siloxanes, which do not have marked volatility, but do have good solubility in the silicone waxes according to the invention.
The creamy wax formulations preferably contain 20 to 95% by weight, more preferably 40 to 80% by weight, of the (b) linear or cyclic organosilicon compounds and thus preferably 5 to 80% by weight, more preferably 20 to 40% by weight, of the (a) silicone waxes according to the invention, the % by weight in each case referring to the total weight of the creamy wax formulations.
EXAMPLE 1
200 g of an aminopropyl-terminated polydimethylsiloxane with an amine equivalent weight of 1506 g/mol NH 2 are mixed with 15.4 g of acetone and stirred for 2.5 hours at 26° C. After heating to 54° C., 78 g of technical-grade alkyl ketene dimer, which has been prepared from a mixture of palmitic acid/stearic acid (ca. 30/70), thus providing a radical R 3 of C 14 /C 16 -alkyl, are added. The technical-grade product has a diketene content of 85%, such that a stoichiometry of 1.0:1.0 is established. After cooling to ca. 47° C., an exothermic reaction starts, which heats the reaction mixture by around 17° C. The alkyl ketene dimer is dissolved completely in the process, and the mixture clarifies. After one further hour at 64° C., the acetone is removed in vacuo and the clear molten wax is cooled. This gives 276 g of a brittle wax which has an amount of relatively long-chain C 14 /C 16 -alkyl radicals R 3 of 21% by weight. The alkyl ketene dimer conversion is more than 99% ( 1 H-NMR).
EXAMPLE 2
In accordance with Example 1, this time 200 g of an α,ω-aminopropylpolydimethylsiloxane with an amine equivalent weight of 5236 g/mol NH 2 are mixed with 4.4 g of acetone and stirred for 2.5 hours at 26° C. At 60° C., 22.5 g of the same alkyl ketene dimer as in Example 1 are added in a stoichiometric amount. With slightly exothermic reaction, the mixture becomes clear and, after a further hour at 67° C., the acetone is removed. With a detected alkyl ketene dimer conversion of ca. 99%, 220 g of a wax with a melting point of ca. 48° C., which has an amount of relatively long-chain C 14 /C 16 -alkyl radicals R 3 of 7.3% by weight, are obtained.
EXAMPLE 3
Using 300 g of an α,ω-aminopropylpolydimethylsiloxane (7519 g/mol NH 2 ) and 4.6 g of acetone, Example 2 is repeated but this time adding 23.5 g of the same alkyl ketene dimer in a stoichiometric ratio. Identical work-up gives 320 g of a silicone wax with a melting point of ca. 47° C., which has an amount of relatively long-chain C 14 /C 16 -alkyl radicals R 3 of 5.2% by weight.
The solubility of the silicone wax according to the invention in a silicone oil is investigated. For this, the amounts of silicone wax stated in the table are added to 100 g of dimethylpolysiloxane with trimethylsiloxane end groups and a viscosity of 35 mm 2 /s at 25° C. The results are summarized in the table.
EXAMPLE 4
The procedure of Example 3 is repeated except that the aminosiloxane is reacted with 27.0 g of a technical-grade alkyl ketene dimer, which corresponds to Example 1 but with the difference that its diketene content is only 75%. In a stoichiometric reaction, a quantitative conversion of the alkyl ketene dimer is also achieved again. Identical work-up gives 324 g of silicone wax with a melting point of ca. 45° C., which has an amount of relatively long-chain C 14 /C 1-6 -alkyl radicals R 3 of 5.2% by weight.
EXAMPLE 5
300 g of a long-chain α,ω-aminopropylpolydimethyl-siloxane with an amine equivalent weight of 15380 g/mol NH 2 (414 Me 2 SiO units) are stirred with 2.3 g of acetone for 2.5 hours at 26° C. The addition of 13.2 g of the 75% strength alkyl ketene dimer used in Example 4 at 60° C. produces only a slightly exothermic reaction over the course of 4 minutes. Postreaction for one hour and removal of the acetone in vacuo produces 310 g of silicone wax with a melting point of 45° C., which has an amount of relatively long-chain C 14 /C 16 -alkyl radicals R 3 of only 2.6% by weight.
Comparative Experiment 1
At 80° C., a total of 184.5 g of an α,ω-dihydrosiloxane with a content of Si-bonded hydrogen of 0.0542% by weight is metered into a solution of Karstedt catalyst (corresponding to 2.0 mg of platinum) in 30.3 g of 1-octadecene, and the mixture is left to postreact for one hour at 100° C. The IR spectrum confirms an SiH conversion of >99%. This gives a clear brownish liquid with a viscosity of 85 mm 2 /s at 25° C. The alkylsilicone comprises 12% by weight of Si-bonded octadecyl radicals, i.e. considerably more than in the products according to the invention of Examples 2 to 5 and is liquid despite the relatively long alkyl chain.
Comparative Experiment 2
The procedure of Comparative Experiment 1 is repeated except that this time 1-octadecene is reacted with 32.8 g of an α,ω-dihydrosiloxane with a content of Si-bonded hydrogen of 0.305% by weight. At a final concentration of 7 ppm of SiH, 99.6% conversion is reached. The slightly brownish liquid with a viscosity of 24 mm 2 /s at 25° C. comprises 44% by weight of Si-bonded octadecyl radicals, far more than the product according to the invention from Example 1, but is still liquid despite this high alkyl content.
Solubility of the Silicone Waxes in Silicone Oil
Example and Comparative Experiment 3
The solubility of the silicone wax according to the invention and of a standard silicone wax in a silicone oil is investigated. For this, the amounts of the silicone wax from Example 3 stated in the table are added at 50° C. to 100 g of dimethylpolysiloxane with trimethylsiloxane end groups and a viscosity of 35 mm 2 /s at 25° C.
In Comparative Experiment 3, a standard wax, an octa-decylmethylsiloxane with trimethylsiloxane end groups (melting point of 43° C.), likewise in the amounts stated in the table, is added at 50° C. to 100 g of the same silicone oil, a dimethylpolysiloxane with trimethyl-siloxane end groups and a viscosity of 35 mm 2 /s at 25° C. The results are summarized in the table.
TABLE
Solubility of the silicone waxes in silicone oil
Amount in 100 g
Solubility in
Wax as in
of silicone oil
silicone oil
Example 3 (wax
0.5
g
Clear
according to the
1.5
g
Clear
invention)
15
g
Clear
35
g
Clear
Comparative
0.5
g
Clear
Experiment 3
1.5
g
Cloudy
(standard wax)
15
g
2-phase
35
g
2-phase
Whereas the silicone wax according to the invention dissolves in silicone oil to give a clear solution, thus has retained its silicone character, the standard silicone wax as in Comparative Experiment 3 is no longer soluble in silicone oil, i.e. has lost its silicone character.
EXAMPLE 6
50 g of the silicone wax from Example 3 are dissolved at 60° C. in 150 g of decamethylcyclopentasiloxane (D 5 ). Upon cooling, a creamy-soft wax formulation of firm consistency, which consists of 75% by weight of the low viscosity D 5 , is obtained.
Consequently, with the silicone wax according to the invention, a “gelling” of volatile cyclic siloxanes is achieved. | Long chain β-ketocarbonyl-functional organosilicon waxes are easily synthesized from organosilicon compounds bearing a reactive hydrogen bonded to N, O, or S, with a diketene. The products remain silicone-like despite being waxy, and can be used to gel low viscosity silicones to creamy formulations useful in cosmetics. | 2 |
CROSS REFERENCE TO RELATED APPLICATION
The present application is based upon and hereby claims priority to U.S. Provisional Patent Application No. 61/680,870, filed Aug. 8, 2012 and the content of said Provisional patent application is hereby incorporated herein by reference in its entirety.
BACKGROUND OF THE INVENTION
Many different patient support systems and sleep platforms have been designed that utilize individual or group bladder control to support a sleeper. The health benefits and sleep benefits of reducing pressure points on a sleeper are well documented. Such sleep platforms attempt to measure the force on a bladder, or a group of bladders, and reduce the pressure in the corresponding bladder(s) to effect pressure reductions in areas where high sleeper interface forces are detected.
Skinner et al., U.S. Pat. No. 7,883,478 describe a patient support having real time pressure control. Each bladder in this support is subtended by a force sensor that is able to sense a force that is transmitted through the inflatable bladder. The apparatus uses the force sensors to determine position and movement of a person lying on the bladders so that the bladder air pressure can be adjusted to match the person's position and movement. The apparatus controls individual bladder sections with individual pneumatic valves
Bobey et al., U.S. Pat. No. 7,698,765 describe a patient support having a plurality of vertical, inflatable bladders. The support system has an interior region that is defined by a top portion and bottom portion of a cover that define an interior region. Within the interior region can shaped bladders and force sensors are provided. The force sensors configured to measure pressure applied to one or more of the bladders. A separate sensor sheet is required to be external to the base and internal to the interior region that subtends the bladder region. Pressure transducers may be coupled to an individual bladder to measure the internal pressure of fluid within the bladder.
Gusakov, U.S. Pat. No. 5,237,501 describes an active mechanical patient support system that includes a plurality of actuator members that are controlled via a central processor. Associated with each actuator is a separate displacement transducer for determining the extension of the actuator. In addition, each actuator has a separate force sensor for determining the force on that actuator. A control means is provided to control the displacement of each actuator connected or integral to each actuator. In addition to individual force sensors associated with each individual actuator, a separate displacement transducer is utilized to determine the exact extension of each actuator member. This displacement transducer is required since the actuator is of a style that approximates a cylinder actuator. When loaded with a constant mass a cylinder actuator will maintain a constant subtended force measurement regardless of variations in the cylinder extension. Therefore, in order to determine the cylinder height, a displacement transducer is required.
Kramer et al., U.S. Pat. No. 7,409,735 describe a cellular person support surface. The support surface is composed of a plurality of inflatable cells, each of which has an associated pressure sensor corresponding to one of the plurality of inflatable cells. At the same time, each inflatable cell has one associated driver corresponding to one of the plurality of inflatable cells that is capable of inflating and deflating the associated cell. The patent requires an individual pressure sensor, as well as an individual inflation and deflation driver for each cell, or group of cells, that is being controlled. In the case of this patent, the sensors and drivers are located within the internal walls of the associated cell.
All of the existing patient support systems and sleep platforms suffer from the high cost and complexity associated with requiring individual control means, displacement transducers, and force sensors for each actuator. To mitigate this cost and complexity, some of these existing patient support systems and sleep platforms propose distributing both the control means and sensing means over multiple bladders or actuators. This requires that the multiple bladders or actuators be fluid coupled to one another and have one fluid stream interconnected between the multiple bladders. This results in a decreased ability to control and sense small areas of the sleep surface. The effect is an increased granularity in both sense and control of the sleep surface. Furthermore, the control means for controlling each actuator's displacement is both expensive and complex. The primary function of the subtended force sensors is to determine sleeper location and position, as well as absolute sleeper weight.
In all of the existing patient support systems and sleep platforms, a pressure sensor that subtends an actuator or bladder, or group of actuators or bladders, continues to read a constant force as long as the sleeper maintains his or her position. Some existing patient support systems and sleep platforms attempt to reduce the actuator pressure when a determination has been made, via the subtended force sensors, that the associated actuator or bladder is being subjected to forces above some established threshold force. By reducing fluid volume in the corresponding bladder, the height of that same bladder is also reduced. Once the fluid volume is reduced so that the corresponding height of the bladder is reduced to a level equal or below the surrounding bladders, the load on the bladder is partially or fully transferred to the surrounding bladders. This results in a pressure reduction on the sleeper from the above threshold bladder.
Beds and Mattresses have remained virtually unchanged over the centuries. Featherbeds are, from a technological point of view, little different from foam or spring beds. Once the aesthetically pleasing quilted mattress cover or ticking is removed, the actual active mattress components are little more than passive spring systems functioning in a similar manner to that of the feathers in a featherbed. All mattresses, whether they are made of individual coil springs, pocket coil springs, high tech foam, overall spring assemblies, or air bladders with adjustable firmness settings, passively adjust to a sleepers' movement. Even accounting for the latest adjustable firmness air bladder mattresses, the resulting active mattress component is nothing more than an adjustable firmness passive air spring. It is generally accepted that reducing high pressure points increases comfort and hence results in better sleep. Beyond reducing pressure points, no other active system has been proposed to improve sleep patterns. A sleep system that can optimize the underlying pressure profile of the sleeper in order to adaptively improve the resultant sleep patterns over several hours or days of sleep is needed.
SUMMARY OF THE INVENTION
The present invention provides a pressure adjustable platform system and methods for adjusting the interface pressure between the support surface and an individual on the surface as well as methods for optimizing the contour of the interface pressure between the support surface and an individual on the surface. Such methods for optimizing the contour of the interface pressure between the support surface and an individual on the surface may provide better quality of rest or sleep and may effectively constitute methods for optimizing or improving sleep.
In one aspect, the present invention provides a method of optimizing a pressure contour of a pressure adjustable platform system by (a) measuring pressure in a plurality of bladders in the pressure adjustable platform system; (b) assessing whether a change in pressure in one or more of the plurality of bladders occurs; (c) determining whether a subject on the pressure adjustable platform system has adjusted position, moved or tossed; (d) generating an adaptive sleep algorithm; and (e) adjusting the pressure in one or more bladders.
The method may further include after (b), determining a number of the plurality of bladders experiencing a change in pressure. Also, the method may further include after (d), providing a pressure image of the subject on the pressure adjustable platform system. The method may further include after (d), providing a pressure profile curve. The (c) determining whether a subject on the pressure adjustable platform system has adjusted position, moved or tossed may be performed by determining the number of bladders that have experienced a significant change in pressure. A significant change in pressure may be at least a 5%, 10%, 15%, 20% or so fluctuation in pressure within a bladder.
The (d) generating an adaptive sleep algorithm may be performed by generating a total sleeper movement number (TSMN). Such a total sleeper movement number (TSMN) may reflect quality of sleep, and the total sleeper movement number (TSMN) may be repeatedly generated. In some instance, the (e) adjusting the pressure in one or more bladders may be performed using a pressure profile curve. The method may also further include after (d), providing a position profile curve. The (d) generating an adaptive sleep algorithm may include the steps of quantifying minor tosses and major tosses. In many instances, the (e) adjusting the pressure in one or more bladders is performed repeatedly, and the time between one or more repeats is measured.
The methods may further include assessing quality of sleep of an individual on the pressure adjustable platform system, and the assessing quality of sleep of an individual on the pressure adjustable platform system may include calculating a total sleep movement number (TSMN) a sleep movement time (SMT) and a sleep quality number (SQN).
The methods may be especially useful when practiced with a pressure adjustable platform system having a plurality of bladders, a base plate, and a plurality of fluid channels wherein the fluid channels connect the bladders to an external sensor, wherein internal pressure of a plurality of the bladders may be adjusted.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view with a cutaway showing the bladder assembly of a sense, react, and adapt sleep apparatus.
FIG. 2A is an exploded front view of the sense, react, and adapt sleep apparatus of FIG. 1 .
FIG. 2B is an exploded top perspective view of the sense, react, and adapt sleep apparatus of FIG. 1 .
FIG. 2C is an exploded bottom perspective view of the sense, react, and adapt sleep apparatus of FIG. 1 .
FIG. 3A is a front view of one embodiment of a hybrid bladder utilizing a mesh on the bottom section.
FIG. 3B is a perspective view of the bladder in FIG. 3A .
FIG. 3C is a cross-sectional perspective view on line A-A of FIG. 3A .
FIG. 3D is a front view of the bladder in FIG. 3 shown in an inflated form due to fluid inflation.
FIG. 4A is a front view of one embodiment of a hybrid bladder composed of a bellows bottom section.
FIG. 4B is a perspective view of the bladder in FIG. 4A .
FIG. 4C is a cross-sectional perspective view on line A-A of FIG. 4B .
FIG. 4D is a front view of the bladder in FIG. 4A shown in an inflated form due to fluid inflation.
FIG. 5 is a close-up of the cutaway section of FIG. 1 showing the bladders in a non-inflated state.
FIG. 6 is a close-up of the cutaway section of FIG. 1 showing the bladders in an inflated state.
FIG. 7 is a top view showing the bladder base plate showing the bladder rim recess channels.
FIG. 8A is a perspective bottom view of the bladder base plate showing the sense and supply channels.
FIG. 8B is an enlarged view from FIG. 8A showing the sense and supply channels for individual bladders.
FIG. 8C is an enlarged view from FIG. 8 showing the sense and supply channels that terminate at the interface plate for the FASB sensing and distribution ports.
FIG. 9 is a documented image of a subject sleeping on an adjustable platform system providing an observed pattern with 6 hours of sleep, as shown by the top row of clocks, with each hour broken up into 10 minute time bands. A small “t” indicates a minor toss while a big “T” indicates a major toss. Position changes are indicated by bar movements in the React band.
FIG. 10 is a documented image of a subject sleeping on an adjustable platform system providing an observed pattern, with each hour broken up into 5 minute time bands. A small “t” indicates a minor toss while a big “T” indicates a major toss. Position changes are indicated by bar movements in the React band.
FIG. 11 is another documented image of a subject sleeping on an adjustable platform system providing an observed pattern, with each hour broken up into 5 minute time bands. A small “t” indicates a minor toss while a big “T” indicates a major toss. Position changes are indicated by bar movements in the React band.
FIG. 12 is another documented image of a subject sleeping on an adjustable platform system providing an observed pattern, with each hour broken up into 5 minute time bands. A small “t” indicates a minor toss while a big “T” indicates a major toss. Position changes are indicated by bar movements in the React band.
FIG. 13 is another documented image of a subject sleeping on an adjustable platform system providing an observed pattern, with each hour broken up into 5 minute time bands. A small “t” indicates a minor toss while a big “T” indicates a major toss. Position changes are indicated by bar movements in the React band.
FIG. 14 is another documented image of a subject sleeping on an adjustable platform system providing an observed pattern, with each hour broken up into 5 minute time bands. A small “t” indicates a minor toss while a big “T” indicates a major toss. Position changes are indicated by bar movements in the React band.
FIG. 15 is another documented image of a subject sleeping on an adjustable platform system providing an observed pattern, with each hour broken up into 5 minute time bands. A small “t” indicates a minor toss while a big “T” indicates a major toss. Position changes are indicated by bar movements in the React band.
FIG. 16 is another documented image of a subject sleeping on an adjustable platform system providing an observed pattern, with each hour broken up into 5 minute time bands. A small “t” indicates a minor toss while a big “T” indicates a major toss. Position changes are indicated by bar movements in the React band.
FIG. 17A is a picture of pressure images of a body sleeping on an adjustable platform system. This image is of a subject sleeping on the side. The colors are representative of the bladder pressures. The actual bladder pressures can be derived from the associated colors by looking at the color to number graph representation in FIG. 17B . The scale numbers are above the base point pressure of 0.40 psi. A dark purple section that shows 0.7 to 0.8 in the accompanying scale has an actual pressure of (0.40+0.80) about 1.2 psi gauge pressure (above atmosphere). High pressure zones are apparent below the shoulders and backside. It may be desirable to reduce pressure in the backside area via one or more of the pressure curves in an attempt to reduce the number of minor and major tosses.
FIG. 18 is another documented image of a subject sleeping on an adjustable platform system providing an observed pattern, with each hour broken up into 5 minute time bands. A small “t” indicates a minor toss while a big “T” indicates a major toss. Position changes are indicated by bar movements in the React band. Also provided is an adaptive band. The bar height in this band represents which sleep curve is being applied to the sleeper at that point in time.
FIG. 19 is a flow diagram of a process that that optimizes a pressure contour of a pressure adjustable platform system.
FIG. 20 is a continuation of the flow diagram in FIG. 19 .
FIG. 21 is a continuation of the flow diagram in FIG. 20 .
FIG. 22 is a bar graph representation of the adaptive pressure adjustment for pressure curve #1.
FIG. 23 is a bar graph representation of the adaptive pressure adjustment for pressure curve #2.
FIG. 24 is a bar graph representation of the adaptive pressure adjustment for pressure curve #3.
FIG. 25 is a bar graph representation of the adaptive pressure adjustment for pressure curve #4.
FIG. 26 is a bar graph representation of the adaptive pressure adjustment for pressure curve #10.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The methods described herein utilize a computer to monitor every individual pneumatic bladder, or electronic spring, and provide the ability to actively sense and adjust the pressure of every bladder within seconds. At the same time, a sleeper's overall sleep patterns are monitored. Sleeper movements and position changes are charted over the course of a sleep episode. This allows a computer to adapt the individual bladder's pressure to optimize the sleeper's best sleep pattern. Over a period of hours, or as long as multiple episodes, the computer's sleep algorithm fine tunes the sleeper's adaptive sleep system with a resulting deeper sleep pattern with fewer periods of restlessness and wakening. This sleep improvement is quantified by analyzing the number of sleep movements and position changes over a known time period. Hour to hour and day to day improvements can be quantified by a reduction in the number of sleeper movements and position changes. In essence, the present methods allow quantifying a more “restful night” of sleep. These improved adaptive sleep patterns are charted over the course of a night's sleep. The sleeper can witness his or her actual sleep improvement with the graphical tools provided by the sleep system. The sleep system communicates with an individual via a remote computer or tablet to let them see their sleep improvement. At the same time, adaptive sleep system tools allow the sleeper to monitor, and analyze, their sleep data. The sleeper also has the ability to subjectively rate their night's sleep. The adaptive sleep algorithm takes into account the sleeper's subjective rating in determining the best available sleep pressure curve and sleeper profile.
All bladders are inflated to a base pressure before the individual moves onto the mattress and it is unloaded. The base pressure may be, for instance, 0.20, 0.30, 0.40, 0.50, 0.60 or so pounds per square inch (psi) above atmosphere. All pressures are defined as gauge pressure (gauge pressure=total pressure−1 atmosphere). At this time a total sleeper movement number (TSMN), that keeps track of the number of tosses and turns of a sleeper, is initialized to zero. A sleeper movement timer (SMT) that measures when the TSMN was last reset to zero is also set to zero and started to begin measuring elapsed time in, for instance, minutes. A sleeper quality number (SQN) that measures the quality of sleep (SQN=1/(TSMN/SMT)) is also reset to zero.
All bladder pressures are measured and recorded in a first table. It is possible, for instance, to read about 150 or so bladders for a queen size mattress in 2 seconds (30 rpm on the valve reading all 150 bladders). In some instances, there may be about 200, 300, 400, 450, 500, 550 or so bladders present in a queen size mattress. Generally, the greater the number of bladders, the finer the granularity of pressure readings and pressure control.
After about 4 seconds (2 rotations of the control valve), the bladder pressures are measured again, and the pressure values are stored in a second table. The pressure values for each bladder from the first and the second table are compared. If a value deviation between an individual bladder's two readings as recorded in the first and second table is greater than about 5%, 10%, 15%, 20%, 25% or so, preferably greater than about 10%, then it is possible to conclude that a significant change in pressure on the associated bladder has occurred. Next, it is possible to assess or total all of the significant pressure changes for all bladders.
If less than a preset number, for instance, 2, 5, 10, 15, 20, 25 or so, preferably 5, bladders have seen a significant pressure change then it is possible to judge that an individual has experienced minimal or no movement. The number of bladders used to determine if a movement has occurred is subject to the number of the total number of bladders on the platform and the size of the platform.
If greater than a preset number, for instance, 2, 5, 10, 15, 20, 25 or so, preferably 5, bladders have experienced a significant pressure change, then it is possible to judge that a small movement or toss has occurred for the individual. In this case, a minor toss “t” may be recorded along with the respective time into an individual's position table. At the same time, it is possible to increment a counter (mintoss) that keeps track of the total number of minor tosses. (mintoss=mintoss+1).
If greater than a preset number, for instance, 2, 5, 10, 15, 20, 25 or so, preferably 10, bladders have experienced a significant pressure change then it is possible to judge that a significant toss or actual turn of the sleeper has occurred. In this case, a major toss “T” may be recorded along with the respective time into an individual's position table. At the same time, it is possible to increment a counter (majortoss) that keeps track of the total number of major tosses. (majortoss=majortoss+1).
An image recognition algorithm may be used to determine an individual's position based upon the pressure values in the second table. The bladders on the platform form a bladder matrix, similar to how pixels on an image sensor form an image matrix. The actual bladder pressures can be translated into corresponding colors based upon their individual pressure values. The resultant image generated is a pressure image of an individual's position. This pressure image is compared to a known position pressure images for the individual, or in the case of no individual data a generic individual pressure map, to find a best match. The resulting image match may be used to determine which predetermined position the individual has assumed. Based upon the above position determination, it is possible to determine if the sleeper has changed positions from his or her last known position. If yes, the new position and time of position change is recorded in the sleeper's position table. If a position change has occurred then a counter (poschange) that keeps track of the total number of position changes (poschange=poschange+1) is entered.
An adaptive sleep algorithm may be generated. For purposes of the adaptive sleep algorithm, weighted values are assigned to minor tosses, major tosses, and position changes. A minor toss has a multiplier of 1. In some instances, a major toss has a multiplier of 5 while a position change has a multiplier of 5. By multiplying the number of minor tosses by their multiplication factor, adding the number of major tosses times their multiplication factor, and adding in the number of position changes by its multiplication factor, a new value for the total sleeper movement number (TSMN) is generated.
TSMN=(mintoss*1)+(majortoss*5)+(poschange*5).
The SQN (SQN=1/(TSMN/SMT)) may be calculated. As long as the SQN is greater than about 4 or 5 or 6, preferably, SQN>6, then the individual is considered to be experiencing a good quality of sleep. Therefore, no adjustments are made to the adaptive pressure profile. However, if the SQN is less than or equal to about 6, then an adaptive pressure profile adjustment is implemented.
A pressure profile curve is composed of a series of bladder pressure value adjustments based upon a given bladder pressure. In some instances, some of the pressure curves adjust as follows:
TABLE 1
Pressure Curve #1 (Default):
Bladder Pressure
Percentage Adjustment
psi
% of measured value
>1.50
50%
1.3-1.50
55%
1.1-1.29
60%
.90-1.09
70%
.70-.89
85%
.60-.69
90%
.50-.59
95%
<.50
100%
FIG. 22 is a bar graph representation of the adaptive pressure adjustment for pressure curve #1. Noting the height difference between the before and after bar charts demonstrates how the bladders that are at higher pressures have their pressures reduced proportionately more than those at lower pressures. Reducing pressure in bladders that read high non-adjusted pressures results in a physical lowering of the heights of these bladders. As the bladder height is reduced, the load on that bladder is partially transferred to the adjoining bladders in effect reducing the high pressure points on the sleeper by distributing the high pressure load to adjoining bladders.
TABLE 2
Pressure Curve #2:
Bladder Pressure
Percentage Adjustment
psi
% of measured value
>1.50
40%
1.3-1.50
45%
1.1-1.29
50%
.90-1.09
60%
.70-.89
75%
.60-.69
80%
.50-.59
85%
<.50
100%
FIG. 23 is a bar graph representation of the adaptive pressure adjustment for pressure curve #2. Noting the height difference between the before and after bar charts demonstrates how bladders that are at higher pressures have pressures reduced proportionately more than those at lower pressures. The higher pressure bladders in curve#2 are reduced by a greater factor than those in curve#1.
TABLE 3
Pressure Curve #3:
Bladder Pressure
Percentage Adjustment
psi
% of measure value
>1.50
30%
1.3-1.50
35%
1.1-1.29
40%
.90-1.09
50%
.70-.89
65%
.60-.69
75%
.50-.59
95%
<.50
100%
FIG. 24 is a bar graph representation of the adaptive pressure adjustment for pressure curve #3. Noting the height difference between the before and after bar charts demonstrates how bladders that are at higher pressures have pressures reduced proportionately more than those at lower pressures. The higher pressure bladders in curve#3 are reduced by a greater factor than those in curve#2. The end result for curve #3 is that all pressures are normalized after adaptation.
TABLE 4
Pressure Curve #4:
Bladder Pressure
Percentage Adjustment
psi
% of measure value
>1.50
30%
1.3-1.50
30%
1.1-1.29
50%
.90-1.09
70%
.70-.89
80%
.60-.69
80%
.50-.59
90%
<.50
100%
FIG. 25 is a bar graph representation of the adaptive pressure adjustment for pressure curve #4. Noting the height difference between the before and after bar charts demonstrates how bladders that are at higher pressures have pressures reduced proportionately more than those at lower pressures. However, unlike the pressure curves 1-3, the middle bladder pressure zones are not adjusted as much in the prior curves. The result provides an after adaptation bar graph with a hump in the middle pressure zone bladders. This represents a departure from the scheme of curves 1-3 and presents a different pressure adaptation path.
TABLE 5
Pressure Curve #10:
Bladder Pressure
Percentage Adjustment
psi
% of measure value
>1.50
70%
1.3-1.50
75%
1.1-1.29
80%
.90-1.09
85%
.70-.89
95%
<.70
100%
FIG. 26 is a bar graph representation of the adaptive pressure adjustment for pressure curve #10. Noting the height difference between the before and after bar charts demonstrates how the bladders that are at higher pressures have pressures reduced proportionately more than those at lower pressures. However, the pressure reduction based upon curve #10 maintains substantial pressure differences between high and low pressure bladders after adjustment. Unlike curve #3 above, the bladder pressures are not normalized after adaptation. This represents a departure from the scheme of curves 1-4 and presents a different pressure adaptation path.
If the SQN is less than or equal to about 4, 5 or 6, preferably 6, then an adaptive pressure adjustment may be made by choosing a different pressure profile curve than the current curve. The pressure profile curve determines the amount of adjustment that is made to a bladder given the magnitude of the individual bladder's pressure reading. For example, from the default pressure curve #1 above, a bladder having a pressure of 1.5 psi may be adjusted downwards to 50% of its value (0.75 psi), while a bladder showing a pressure of 1 psi may be adjusted downwards to 70% of its value (0.7 psi). Once a specific curve is used to adjust the actual bladder values, the TSMN is monitored over time.
After an adaptive pressure adjustment is made and a curve is applied to the bladders to adjust their pressures the TSMN, SMT, mintoss, majortoss, and poschange are reset to zero. OLDSQN is set equal to SQN (OLDSQN=SQN) to keep a record of the quality of sleep prior to the latest adaptive pressure adjustment.
Any bladder that experiences a pressure reading below the base pressure of about 0.40 psi may be inflated back to the base pressure of about 0.40 psi. A bladder may fall below the base point after a pressure being exerted on the bladder is removed from the bladder because air may have been removed during the adaptive phase. Once the pressure is ultimately removed from the bladder, air may be reinserted to increase pressure back to the base point pressure (about 0.40 psi).
SQN changes are monitored over the course of a sleep period. If SQN>OLDSQN then the adaptive sleep pressure adjustments are improving the quality of sleep for the individual. This further indicates that progress in the right direction towards a better individual pressure profile curve. As long as the SQN>OLDSQN, curves will be picked that move in the direction of this improvement. Conversely, if SQN<OLDSQN, then curves will be picked that go in a different direction from the prior ones chosen. For instance, if curve #1 was chosen and provided an improvement (SQN>OLDSQN), curve#2 was chosen and provided an improvement (SQN>OLDSQN), curve#3 was chosen and provided a negative improvement (SQN<OLDSQN), then curve #2 might be chosen again. If the improvement is still not at a target value, (target value is SQN>6), then another group of curves might be chosen that provides different ratio of bladder pressure to pressure reduction, in this case curves 4-10.
For a further refinement in determining the best possible individual pressure profile, it is also possible to superimpose a position profile curve on top of the pressure profile curve. A position profile curves adds bladder based pressure reductions based upon the individual's sleep orientation (sleeping on back, side, or front) as determined in step #9 above. For example, when an individual is on his or her back, bladders underlying the individual's gluteus maximus may need to be reduced by a greater factor than those underlying the shoulders. In this case the accompanying position profile curve may have a multiplication factor for bladders based upon their position underneath the sleeper. As an example, bladders that are determined to be under the gluteus maximus in this case may have a pressure reduction that is multiplied by 1.2 times. As a result, a bladder that was originally at 4 psi and was reduced 50% to 2 psi by the pressure profile curve, will after application of the position profile curve be reduced to a final pressure of 1.7 psi that is 42% (4*(0.5/1.2)) of its original value. Bladders that underlie the shoulders may have a pressure reduction that is multiplied by 1 and therefore remain unchanged from their pressure profile curve values. If after superimposing a position profile curve on top of the pressure profile curve, the SQN does not improve, the position profile curve may be removed. If the SQN increases, then the position profile curve may be used in addition to the adaptive pressure profile curves.
At some point, the SQN will not trend any lower. This might even occur if the SQN<=6. At this point, the associated pressure profile curve is identified as the best adaptive sleeper profile curve for this individual.
The SQN for an individual may be monitored into the future to determine if further adaptation and adjustment yields sleep quality improvement. At the same time, the individual's own subjective assessment of his or her sleep will influence the adaptive sleep algorithm adjustment. For example, if an individual indicates that he or she slept well regardless of the SQN number trending lower, that individual's profile curve may not be changed until further subjective assessment that asks for further profile curve improvement is provided.
The methods may be understood with reference to the flow diagrams provided in FIGS. 19 , 20 and 21 which depict exemplary embodiments. FIG. 19 is a flow diagram of a process that that optimizes a pressure contour of a pressure adjustable platform system. The process is started in step 200 . Prior to a sleeper getting on the platform, all of the bladders are pressurized to 0.40 psi gauge pressure in step 202 . All variables are initialized to zero values, and an initial pressure profile curve is chosen and set to curve #1 by default. This assumes that a stored known pressure profile for the sleeper does not exist. A sleeper movement timer (SMT) is started in step 205 . This timer measures the elapsed time between adaptive pressure profile adjustments. All of the platform bladders pressures are read and stored in a table designated table 1 in step 208 . The table may be a two dimensional table that provides an x and y label for each entry that corresponds to the bladder position on the platform. After a four second wait in step 210 , the pressures of the platform bladders are read again and stored in a table designated table 2 in step 212 . The same physical bladders on the platform occupy the same respective location in each of the two tables. Respective bladder readings are compared in step 216 . If a deviation of greater than 10% exists between the two readings, indicating that a substantive pressure change for that bladder has occurred, then a Bladder Deviation Counter (BDC) is incremented in step 214 . If the deviation is less than or equal to 10% the next bladder's values are compared. After all bladder readings in the two tables are compared, a BDC value is provided and read in step 218 . If the BDC is equal to 5 or less, no significant movement is determined to have occurred on the pressure platform. The process then moves to step 232 that begins the next part of the process in FIG. 20 . If a BDC value of greater than 5 and less than or equal to 10 is read, then a minor toss mintoss is said to have occurred in step 222 . Mintoss is a counter that keeps track of the total number of minor tosses. After incrementing the mintoss counter the process progresses to step 232 . If a BDC value of greater than 10 is recorded, then a major toss majortoss is said to have occurred in step 220 . Majortoss is a counter that keeps track of the total number of major tosses. A sleeper pressure image is then created in step 224 . This image is compared to known position pressure images for this sleeper, or in absence of such images, to a stock database of position pressure images in step 226 . Once a best match position is determined, this position is compared to the last known position in step 228 . If no position change has occurred, the process progresses to step 232 . If a position change has occurred, a counter poschange is implemented in step 230 . Poschange is a counter that keeps track of the total number of position changes. The last known position is set to the new position in step 234 , and the process proceeds to step 232 .
FIG. 20 is a continuation of the flow diagram in FIG. 19 . The continuation of step 232 FIG. 19 continues in step 250 . The Total Sleep Movement Number (TSMN) is calculated in step 252 . The TSMN takes into account individual scale factors for minor and major moves as well as position changes. A Sleeper Quality Number (SQN) is calculated in step 254 . The SQN includes SMT with the TSMN to determine a quantitative measurement of the sleep quality. The TSMN value is tested in step 258 . If the value is less than 10, then the process returns via step 256 to step 206 FIG. 19 . The SQN value is tested in step 262 . If the value is greater than 6, then the process returns via step 260 to step 206 ( FIG. 19 ). In both cases above, returning to step 206 ( FIG. 19 ) is because the sleep quality is determined to be high and above a threshold that dictates that adaptive pressure adjustment is not required at this time. In step 264 , the Old Sleeper Quality (OLDSQN) is compared to the SQN. If OLDSQN>SQN then a new pressure curve direction is taken in step 266 where the Pressure Profile Curve Counter (PPCC) is changed to point to a set of Pressure Profile Curves (PPC) that takes the adaptive algorithm in a new direction. If SQN>=OLDSQN, then the process continues within the current pressure profile curve direction and increment the PPCC in step 268 to point to the next curve within the current adaptive algorithm direction. After completing step 266 or 268 , the new PPC is chosen from the new PPCC number in step 270 . At step 272 , each bladder's pressure on the platform is read. If the bladder pressure is less than or equal to the base point pressure of 0.40 psi, then that bladder is inflated to 0.40 psi in step 276 . If the bladder pressure is greater than 0.40 psi then that bladder's pressure is set to a new pressure factoring in the PPC value for this bladder in step 274 . Once all the bladders on the platform are read and adjusted, the variables are reset to zero in step 278 . The SMT is restarted in step 280 . OLDSQN is set equal to SQN in step 282 and the process continues on to step 300 ( FIG. 21 ) in step 284 .
FIG. 21 is a continuation of the flow diagram in FIG. 20 . The continuation of step 284 FIG. 20 continues in step 350 . Whether the sleeper has left the platform is determined in step 352 . If the sleeper has not left the platform, then the process proceeds via step 354 to step 206 ( FIG. 19 ). If the sleeper has left the platform, then the sleeper is questioned for a subjective sleep assessment in step 356 . If the sleeper did not like the sleep experience, then the current OLDSQN is stored in their profile in step 362 , and the adaptive algorithm is stopped in step 368 . If the sleeper did like the sleep experience, then the current OLDSQN is stored in their profile in step 360 . The sleeper's subjective sleep assessment is stored in their profile in step 364 . Step 366 locks the sleeper profile so that no future adaptive correction will be implemented until the sleeper indicates a desire for better sleep. The adaptive algorithm is then stopped in step 368 .
The methods are especially useful with a pressure adjustable platform system as described by Codos, “A Pressure Adjustable Platform System,” U.S. patent application Ser. No. 61/675,496, filed Jul. 25, 2012, herein incorporated by reference. In such a pressure adjustable platform system, each bladder is individually sensed, regulated, and controlled via a central processing unit. Besides the known benefits of reducing pressure points on a sleeper that can result in improved sleep and health benefits, the platform system can be configured to sense and store sleep data that can be used for future pressure sleep profiles that improve the sleeper's quality of sleep.
Such a pressure adjustable platform system reduces the complexity of the fluid distribution and sensing network between the sleep support and a single apparatus that incorporates both the multi-port fluid sensing, as well as the multi-port fluid distributing functions, an example of which is Codos, “Fluid Sensing and Distributing Apparatus” (FSDA), U.S. patent application Ser. No. 61/675,901, filed Jul. 26, 2012, herein incorporated by reference. In some instances, the FSDA valve body is fastened directly into the sleep support base plate to eliminate any tubing interconnections between the sleep support and associated apparatus. This objective is achieved by matching the FSDA apparatus flat distribution plate on which the inlet and output ports are located to a matching port plate on the sleep support. Fluid connections are achieved by mating these two parts and using any one of known means for ensuring a leak-proof connection. In some instances, the distribution plate of the FSDA can be directly built into the sleep support base plate thereby serving effectively as a connection plate and thereby reducing the cost and complexity of the combined sleep support and associated apparatus. A further object of the invention is to affect or control a larger number of bladders that are proportional to larger sleep areas, without significantly increasing the fluid distribution and fluid sensing complexity and associated costs. By incorporating the fluid channels into the sleep support base plate, additional bladders are accompanied by additional corresponding fluid channels into the base plate without adding any additional fluid distribution components.
Such a pressure adjustable platform system reduces the number of components associated with sensing the pressure and displacement for each individual bladder. The requirement that pressure sensors subtend individual bladders or groups of bladders, or the need to provide a measuring sensor for each individual bladder increases the complexity and cost of a sleep system. The added complexity associated with the need for multiple pressure sensors and/or displacement transducers has the added effect of reducing the reliability of the sleep system. By providing a sensor that can be multiplexed to all of the sleep system bladders through an apparatus such as an FSDA apparatus, it is not necessary to provide a large number of sensors that subtend the bladders of the sleep support. An individual sensor may be multiplexed to read, for instance, about 25, 50, 100, 150 or so individual bladders. As a result, in some instances, three sensors may be used for sensing about 150 individual bladders on a sleep support. Bladders communicate with the multiplexed sensor through integrated fluid pathways.
Such a pressure adjustable platform system reduces the number of components required for inflating and deflating associated bladders. Providing an individual driver or actuator for each bladder or gang of bladders increases the complexity, cost, noise, size, and response time of a sleep system. The added complexity associated with the need for multiple actuators or drivers has the added effect of reducing the reliability of a sleep system. By utilizing an actuator that can be multiplexed to all of the sleep system bladders through an apparatus such as an FSDA apparatus, the need for a large number of actuators that communicate with each bladder for this invention is eliminated. An individual solenoid control valve may be multiplexed to fill and deflate approximately 25, 50, 100, or 150 or so individual bladders. As a result, three solenoid control valves that are used in conjunction with an FSDA apparatus are used for controlling for instance, about 150 individual bladders on the sleep support.
Such a pressure adjustable platform system eliminates wiring between the bladders and the force sensors. At the same time, the wiring for the actuators needed to increase and decrease pressure to the individual bladders is also eliminated. Instead of wiring, bladders communicate with the multiplexed actuators and sensors through the integrated fluid pathways. A single fluid channel connects each bladder to the external fluid sensing and distributing apparatus and is the only conduit needed for sensing pressure in the bladder, providing fluid and exhausting fluid to the bladder.
Such a pressure adjustable platform system provides a bladder that combines the characteristics of an extendable cylinder with the characteristics of an expandable bladder. An extendable and retractable cylinder maintains a constant internal pressure value regardless of its amount of extension for a given loaded mass. When subjected to a constant external load, an extendable and retractable cylinder transmits a force through a fluid channel connected to the cylinder that is proportional to the applied load. Reducing air in the cylinder only reduces the height of the cylinder without reducing the internal pressure. By contrast, when an expandable bladder is subjected to a constant external load, the bladder deforms in shape while transmitting only a small portion of the applied force through a fluid channel connected to the bladder. It is desirable to utilize a fluid coupled remote sensor to measure the force on a bladder in response to an applied load. A retractable cylinder style bladder achieves this result. It is also desirable to create a bladder that deforms so that it contacts adjoining bladders. This inter-bladder contact helps transfer loads to adjoining bladders while increasing lateral stability and decreasing lateral movement of the sleeper. An expandable bladder accomplishes this goal. It is therefore an object of this invention to combine these two bladder types into a single hybrid bladder.
Such a pressure adjustable platform system provides a sleep support composed of bladders in which each bladder is individually sensed, regulated, and controlled via a central processing unit. Besides the known benefits of reducing pressure points on a sleeper that can result in improved sleep and health benefits, the sleep system can be configured to sense and store sleep data that can be used for future pressure sleep profiles that improve the sleeper's quality of sleep.
FIG. 1 depicts such a pressure adjustable platform system 10 that includes a top cover 12 . The cover 12 may be made of a knitted material, cotton, polyester fibers, or a woven or needle punched fabric, and the cover 12 may be quilted or not quilted. Below the cover 12 is a layer of foam padding 14 . The foam padding 14 may be a polyurethane foam of medium density. Below the foam padding 14 is a sisal layer 16 . A variety of other padding materials, other combinations of padding and insulating materials, and various cover materials and constructions may be used.
Below the padding 14 and cover 12 materials are provided hybrid pneumatic bladders with sidewalls 30 that are encased in a mesh 31 on the bottom portion of the bladder. The mesh 31 restricts a portion of the bladder from expanding outward by some limit when subjected to increasing internal air pressures. At the same time, the mesh 31 allows the same portion of the bladder to collapse upon itself. As a result, this portion of the bladder transmits forces through a fluid conduit back to a pressure sensor when subjected to external loads. This may be similar to the manner in which a rigid wall pneumatic cylinder transmits forces through a fluid conduit when subjected to an external load.
The bladders are located on a base plate 24 that has recessed slots that correspond to the individual bladder positions. The individual bladders may be replaced by a group of bladders that are attached to one another by an integral bladder base membrane. This multiple bladder sheet may be molded as a single piece with the added benefit of reducing manufacturing costs associated with individual bladder construction. The base plate 24 may have recessed slots corresponding to the multiple bladder configurations. The bladder may have any suitable diameter allowing for an increased or decreased number of bladders for a given mattress size. The end result of a greater number of bladders is a mattress having a larger number of sense and control points therefore decreasing the granularity of the sense and react function and increasing the control over the sleep area.
The bladders may be secured to the base plate 24 by a bladder top plate 18 , which clamps the bladder to the base plate 24 by clamping the bladders' flange to the base plate 24 . The entire bladder assembly rests on a box top plate 22 . The box top plate 22 serves to seal the fluid conduits that are part of the lower side of the base plate 24 , as well as provide structural support for the entire bladder assembly. The box top plate 22 forms the top surface of the box assembly 20 , which provides structural support for the entire sense, react, and adapt sleep apparatus, along with the associated sleepers.
FIG. 2A provides a front expanded view of such a pressure adjustable platform system 10 of FIG. 1 . In addition to those components visible in FIG. 1 is also a fluid sensing and distributing apparatus 28 described in Codos, “A Fluid Sensing and Distributing Apparatus,” U.S. patent application 61/675,901, filed Jul. 26, 2012, hereby incorporated by reference. The fluid sensing and distributing apparatus 28 is fastened directly to the base plate 24 through a matching gasket plate 29 . This direct connection of the fluid sensing and distributing apparatus 28 to the base plate 24 through the gasket plate 29 eliminates any tubing interconnections. The distribution plate of the fluid sensing and distributing apparatus 28 can be directly built into the base plate 24 thereby eliminating the need for a gasket plate 29 . FIG. 2B provides an expanded top perspective view of FIG. 1 . The bladder top plate 18 clamps the bladders to the base plate 24 by clamping the flange 33 on the bladder into the bladder locating slot 48 that is recessed into the base plate 24 . FIG. 2C provides an expanded bottom perspective view of FIG. 1 . Visible in this view is the bottom side of base plate 24 revealing the fluid channels 50 that convey fluid between the bladders and the fluid sensing and distributing apparatus 28 .
FIG. 3A is a front view of the bladder 26 and mesh 31 described herein. The bladder may be made from a silicon rubber compound with a shore A hardness of for instance, about 10A, 20A, 30A, 40A, 50A, etc. The bladder wall thickness may be about 0.05, 0.1, 0.2, 0.25, 0.3, 0.5 or so inches, with about a 2.0, 3.0, 4.0, 4.5, 4.75, 5.0 or 6.0 inch diameter and about a 2.0, 3.0, 3.5, 4.0 or 5.0 inch height. The mesh may be made from a polyethylene plastic material approximately 1/16 inch in thickness. The mesh height may extend about 1.0, 1.25, or 1.50 or so inches from the top of the flange 33 . The bladder's sidewall 30 is in its non-inflated state. This non-inflated state is defined as having an internal pressure in the bladder equal to, or less than, the external atmospheric pressure that is exerted upon the bladder. Bladder flange 33 , which may be about 0.25, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8 or so inches wide and about 0.1, 0.2, 0.3, 0.4 or so inches thick, is an integral part of the bladder as is used to clamp the bladder to base plate 24 ( FIG. 2A ) thru the clamping action of bladder top plate 18 ( FIG. 2A ) as the top plate is mechanically connected, using any one of known means, to base plate 24 ( FIG. 2A ). These mechanical connection means may be, for instance, screw fasteners, clamp fasteners, or plastic welding of the two plates. Once the bladder flange 33 is clamped to the base plate 24 ( FIG. 2A ), it forms a fluid tight seal between the internal cavity 35 ( FIG. 3C ) of bladder 26 and base plate 24 ( FIG. 2A ).
FIG. 3B is a front perspective view of the bladder 26 showing line A-A. FIG. 3C is a cross-sectional perspective view on line A-A of FIG. 3B . A plastic insert 34 is provided to insure that the top surface 32 of the bladder is maintained in a flat orientation that is parallel to the bladder flange 33 when the bladder 26 is in its non-inflated state, or when the bladder is subjected to an internal fluid pressure that exceeds the external atmospheric pressure (inflated state). Maintaining the top surface 32 of the bladder parallel to the bladder flange 33 insures that forces exerted on an individual are distributed across the entire area of top surface 32 . This insures that pressure points that could otherwise arise from a bulging upper bladder surface are not transmitted through to the individual. The plastic insert 34 may be made from, for instance, an Acetal Resin plastic that may be about 3/32″ thick. It may also be made from, for example, acrylonitrile butadiene styrene plastic, nylon, polyvinyl chloride, or any plastic that is compatible with the silicon rubber of bladder 26 and stiff enough so as to not significantly deflect when subjected to the loaded internal pressures of the bladder. Internal cavity 35 is visible in this view.
FIG. 3D is a front view of the bladder in FIG. 3A shown in an inflated state due to increased internal fluid pressure. The internal fluid pressure is greater than the external atmospheric pressure causing the bladder's sidewall 30 to bulge outward. An increased internal fluid pressure can be the result of an external load applied to top surface 32 , or can be the result of the cpu, via the fluid sensing and distributing apparatus 28 , directing a higher fluid pressure into the respective bladder 26 . The mesh 31 provides the area that it encircles, with resistance to tangential forces that result from the internal cavity 35 ( FIG. 3C ) having an internal fluid pressure greater than the external atmospheric pressure. When the bladder is in an inflated state due to increased internal fluid pressure, mesh 31 underlining the portion of sidewall 30 maintains a perpendicular orientation to flange 33 . When top surface 32 is subjected to external forces, side wall 30 above the mesh bulges outward in direct response to rising internal fluid pressures in the internal cavity 35 ( FIG. 3C ). At the same time, top surface 32 moves closer to flange 33 while remaining substantially parallel to flange 33 . At some loaded pressure, the portion of side wall 30 that lies under the mesh 31 begins to buckle upon itself allowing upper surface 32 to further collapse towards flange 33 without additional bulging of sidewall 30 that lies above the mesh 31 . This buckling action transmits pressure forces, above atmospheric pressure and commensurate with the external force pressure, through a fluid conduit back to a pressure sensor.
FIG. 4A is a front view of an alternative bladder 306 having a bellows bottom section 300 . The bladder functions similar to the bladder 26 of FIG. 3A but does not have the mesh 31 of the bladder 26 of FIG. 3A . Instead of a mesh to constrain the bladder sidewall, a bellows bottom section 300 collapses upon itself when the bladder 306 is subjected to an external force threshold level through a top plate 304 . The bladder may be made, for instance, from a silicon rubber compound with a shore A hardness of, for instance, 10A, 20A, 30A, 40A, 50A, etc. The bladder wall thickness may be about 0.05, 0.1, 0.2, 0.25, 0.3, 0.5 or so inches, with about a 2.0, 3.0, 4.0, 4.5, 4.75, 5.0 or 6.0 inch diameter and about a 2.0, 3.0, 3.5, 4.0 or 5.0 inch height. The bellows 300 is configured such that adjacent corrugated folds are at approximately 90 degrees to one another and plus or minus 45 degrees from vertical, the vertical plane being coincident with sidewall 302 and perpendicular to flange 303 . The bellows height extends about, for instance, 1.25 inches from the top of the flange 303 . The bladder's sidewall 302 is in its previously defined non-inflated state. Bladder flange 303 , which may be about 0.25, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8 or so inches wide and about 0.1, 0.2, 0.3, 0.4 or so inches thick, is an integral part of the bladder that is used to clamp the bladder to the base plate 24 ( FIG. 2A ) through the clamping action of bladder top plate 18 ( FIG. 2A ) as the top plate is mechanically connected, using any one of known means, to the base plate 24 ( FIG. 2A ). In another configuration the angular relationship of the corrugated folds to one another can be other than 90 degrees.
FIG. 4B is a front perspective view of the bladder in FIG. 4A . A cut line A-A is shown.
FIG. 4C is a cross-sectional perspective view on line A-A of FIG. 4B . Plastic insert 308 is provided to insure that the top surface 304 of the bladder is maintained in a flat orientation that is parallel to the bladder flange 303 when the bladder 306 is in its non-inflated state, or when the bladder is subjected to an internal fluid pressure that exceeds the external atmospheric pressure (inflated state). Maintaining the top surface 304 of the bladder parallel to the bladder flange 303 insures that forces exerted on the sleeper are distributed across the entire area of top surface 304 . This insures that pressure points that could otherwise arise from a bulging upper bladder surface are not transmitted through to a sleeper. Plastic insert 308 may be made from an Acetal Resin plastic and about, for instance, 3/32″ thick. The plastic insert 308 may also be formed of acrylonitrile butadiene styrene plastic, nylon, polyvinyl chloride, or any plastic that is compatible with the bladder 306 and stiff enough to not significantly deflect when subjected to the loaded internal pressures of the bladder. Internal cavity 305 is visible.
FIG. 4D is a front view of the bladder in FIG. 4A shown in an inflated state due to increased internal fluid pressure. The internal fluid pressure is greater than the external atmospheric pressure causing the bladder's sidewall 302 to bulge outward. An increased internal fluid pressure can be the result of an external load applied to top surface 304 , or can be the result of cpu via a fluid sensing and distributing apparatus 28 , directing a higher fluid pressure into the respective bladder. The bellows 300 provides that the distance, for instance, 1.00, or 1.25 or 1.50 or so inches, as measured from the top of the flange 303 , with resistance to tangential forces that results from the internal cavity 305 ( FIG. 4C ) having an internal fluid pressure greater than the external atmospheric pressure. When the bladder is in an inflated state due to increased internal fluid pressure, bellows 300 maintains a perpendicular orientation to flange 303 . When top surface 304 is subjected to external forces, side wall 302 bulges outward in response to rising internal fluid pressures in the internal cavity 305 ( FIG. 4C ). At the same time, top surface 304 moves closer to flange 303 while remaining substantially parallel to flange 303 . At some loaded pressure, bellows 300 starts to collapse allowing upper surface 304 to further collapse towards flange 303 without additional bulging of sidewall 302 . This buckling action transmits pressure forces, above atmospheric pressure and commensurate with the external force pressure, through a fluid conduit back to a pressure sensor such as a pressure sensor present in a fluid sensing and distributing apparatus 28 .
FIG. 5 is a close-up of the cutaway section of FIG. 1 showing the bladders in a non-inflated state. This non-inflated state is defined as having an internal pressure in the bladder equal to, or less than, the external atmospheric pressure that is exerted upon the bladder. The bladder 26 represented in FIG. 1 , and this view, is the bladder 26 with mesh represented in FIG. 3A . The bladder's sidewall 30 is substantially perpendicular to the bladder top plate 18 . When the bladders 26 are in a non-inflated state an air gap exists between adjacent bladders 26 . The air gap may be, for instance, about ¾ inch, 1 inch, or 1¼ inch or so as measured between adjacent bladder's sidewalls 30 . Each bladder's sidewall 30 is in a parallel orientation to the adjacent bladder's sidewall 30 .
FIG. 6 is a close-up of the cutaway section of FIG. 1 showing the bladders in an inflated state. This inflated state is defined as having an internal pressure in the bladder greater than the external atmospheric pressure that is exerted upon the bladder. When the bladders 26 are in an inflated state, the bladder's sidewall 30 bulges outward in a direction parallel to the plane of bladder top plate 18 , and tangential to the original sidewall 30 orientation shown in FIG. 5 . As the internal pressure in the bladder increases, the extent of the bulge also increases resulting in a decreased air gap between adjacent bladder sidewalls 30 . The air gap continues to decrease as the internal pressure increases up to the point where sidewall 30 comes into contact with an adjacent bladder's sidewall 30 . At this point the bladder sidewall 30 may continue to expand in an asymmetric manner as it continues to expand in areas not constrained by adjacent bladder sidewalls. One of the effects of having the bladder's sidewall 30 in contact with an adjacent bladder's sidewall 30 is to provide lateral support to the bladder. An additional effect is that some external forces acting upon a bladder are partially transferred to adjacent bladders.
FIG. 7 is a top view of the bladder base plate 24 with the bladder rim recess channels 48 visible. Bladder fill port 52 is visible in the center portion of each bladder location. Bladder rim channel 48 is used to locate the individual bladders as well as provide a recessed channel into which bladder flange 33 ( FIG. 3A ) fits. The channels may be, for instance 0.05, 0.1, 0.2, 0.3 or so inches deep with a width of, for instance, about 0.25, 0.3, 0.4, 0.5, 0.51, 0.6, 0.7 or so inches.
FIG. 8A is a perspective bottom view of the bladder base plate 24 . FIG. 8C indicates where the fluid sensing and distributing apparatus 28 ( FIG. 2A ) is connected directly into the base plate 24 through gasket plate 29 ( FIG. 2 ) eliminating any tubing interconnections with the fluid sensing and distributing apparatus 28 ( FIG. 2A ). The fluid channels 50 convey fluids between the fluid sensing and distributing apparatus 28 ( FIG. 2A ) and the bladders 26 ( FIG. 3A ).
FIG. 8B is an enlarged view showing the sense and supply channels 50 for individual bladders 26 . The bladder fill ports 52 convey fluid from the supply channel to the bladder that is located on the opposite side of the bladder base plate 24 . The bladder supply channels may be, for instance, about 0.1, 0.125, 0.15, or 0.20 inches deep by about, for instance, 0.1, 0.125, 0.15, or 0.20 inches wide while the bladder fill port 52 may be about 0.1, 0.125, 0.15, or 0.20 inches in diameter.
FIG. 8C is an enlarged view showing the sense and supply channels from the fluid sensing and distributing apparatus 28 ( FIG. 2A ) that terminate at the gasket plate 29 ( FIG. 2A ). The interface port 54 hole pattern and hole size matches the hole pattern and hole size in the fluid sensing and distributing apparatus 28 ( FIG. 2A ) distribution plate through a matching hole pattern in the gasket plate 29 ( FIG. 2A ).
The pressure adjustable platform system may be used in conjunction with a fluid sensing and distribution apparatus as described in Codos, “A Fluid Sensing and Distributing Apparatus,” copending U.S. application Ser. No. 61/675,901, filed Jul. 26, 2012, herein incorporated by reference.
The detailed description is representative of one or more embodiments of the invention, and additional modifications and additions to these embodiments are readily apparent to those skilled in the art. Such modifications and additions are intended to be included within the scope of the claims. One skilled in the art may make many variations, combinations and modifications without departing from the spirit and scope of the invention. | The present invention provides a method of optimizing a pressure contour of a pressure adjustable platform system by (a) measuring pressure in a plurality of bladders in the pressure adjustable platform system; (b) assessing whether a change in pressure in one or more of the plurality of bladders occurs; (c) determining whether a subject on the pressure adjustable platform system has adjusted position, moved or tossed; (d) generating an adaptive sleep algorithm; and (e) adjusting the pressure in one or more bladders. | 0 |
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention is directed to chair height adjustment mechanisms. More particularly, the present invention is directed to improvements to the adjustment mechanism described and claimed in U.S. Pat. No. 5,511,759 which is hereby incorporated by reference.
[0003] 2. Brief Description of the Related Art
[0004] Generally, height adjustment mechanisms comprise a piston and a cylinder connected to a reservoir. To telescopically extend the system, fluid is transferred from the reservoir to the cylinder forcing the piston outward. Conversely, to telescopically contract the system, fluid is transferred from the cylinder to the reservoir, drawing the piston inward. A valve between the cylinder and the reservoir controls the flow of the fluid. Typically an incompressible liquid, such as hydraulic fluid, is used. Thus, once the desired height is selected the valve is closed, trapping the fluid in the cylinder and maintaining the desired height position. When the pressure within the reservoir is greater than the outside ambient pressure, a condition known as preload is achieved. Preload forces the piston outward when the valve is open and no load is applied to the piston. This allows a user to extend the height adjustment to its maximum height and then apply a load until the desired height is reached and then close the valve setting the height. An invention of the U.S. Pat. No. 5,511,759 patent uses an expandable elastomeric chamber to provide preloaded pressure to the piston and cylinder such that the device will telescopically expand when the valve is open and the device is not subject to a load.
SUMMARY OF THE INVENTION
[0005] According to a first exemplary embodiment of the present invention, a height adjustment mechanism comprises (a) an outer support tube having a first closed end and a second open end, (b) an inner support tube assembly telescopically received within said outer support tube, said inner support tube assembly including an external tube, an internal tube disposed within said external tube, first means sealing and interconnecting said external and internal tubes at a first pair of ends and second means sealing and interconnecting said external and internal tubes at a second pair of ends thereof, said external tube and said internal tube defining a first chamber there between, (c) a piston assembly interconnected to said outer support tube and telescopically received within said internal tube, said internal tube and said piston assembly defining a second chamber there between, (d) port means allowing fluid flow between said first and second fluid chambers, (e) a hydraulic fluid contained within said port means and said first and second chambers, (f) valve means interactive within said port means for regulating fluid flow between said first and second chambers, and (g) energy storage means including a pressurized fluid cooperating with said first chamber to provide a lift force upon opening said valve means to allow flow of said hydraulic fluid between said outer support tube and said inner support tube assembly.
[0006] According to a second exemplary embodiment of the present invention, a height adjustment mechanism comprises (a) an outer support tube having a first closed end and a second open end, (b) an inner support tube assembly telescopically received within said outer support tube, said inner support tube assembly including an external tube, an internal tube disposed within said external tube, (c) first means sealing and interconnecting said external and internal tubes at a first end including an elastomeric sleeve encircling said internal tube and having a thin, more flexible portion which permits said valve means to be moved between a first closed position and a second open position said first means supporting said valve means and biasing said closeable valve means to said first closed position, (d) second means sealing and interconnecting said external and internal tubes at a second end thereof, said external tube and said internal tube defining a first chamber there between, (e) a piston assembly interconnected to said outer support tube and telescopically received within said internal tube forming a second chamber, (f) port means allowing fluid flow between said first and second fluid chambers, (g) a hydraulic fluid contained within said port means and said first and second chambers, (h) valve means interactive within said port means for regulating fluid flow between said first and second chambers, and (i) a pressurized gas cooperating with said first chamber to provide a preload lift force upon opening said closeable valve to telescopically extend said inner support tube assembly relative to said outer support tube.
[0007] According to a third exemplary embodiment of the present invention, a constant force spring comprises (a) a piston cylinder having a first closed end, (b) a piston received and slidable within said piston cylinder, (c) a first chamber defined between said first closed end of said piston cylinder and said piston, (d) seal means provided on said piston sealing said piston against said piston cylinder making said first chamber substantially leakproof, and (e) a fluid confined within said first chamber, said fluid being in said first chamber will be partially liquid and partially gaseous with vapor pressures at room temperature in the range of between 50 psi and 150 psi such that a compressive force on said first chamber by said piston will cause a portion of said gaseous fluid to move into a liquid state exhibiting a constant force opposing said compressive force.
[0008] According to a fourth exemplary embodiment of the present invention, a means for controlling flow of hydraulic fluid in a piston cylinder comprises a valve member comprising (a) an elastomeric sleeve portion which fits over an inner support tube and seals against said inner support tube to prevent undesired fluid flow between said elastomeric sleeve portion and said inner support tube, said elastomeric sleeve portion including passageway means to permit desired flow of hydraulic fluid between said elastomeric sleeve portion and said inner support tube, said elastomeric sleeve portion fitting within an outer support tube and being sealed with respect thereto to prevent undesired flow of hydraulic fluid between said elastomeric sleeve portion and said outer support tube, (b) a flexible intermediate section interconnected to said elastomeric sleeve portion, (c) a generally tabular portion extending outwardly from said flexible intermediate section, (d) a rigid valve seat element which has i) a stem portion extending through an end portion of said inner support tube, a portion of said stem portion being received within said generally tubular portion, and ii) a flat valve seat projecting from said stem portion that abuts and seals against an inner surface portion of said inner support tube, and (e) a manually engageable valve actuator having a portion which surrounds an upper periphery of said generally tubular portion, whereby when said manually engageable valve actuator is depressed, said generally tubular portion is moved axially unseating said valve seat from said inner surface portion of said inner support tube permitting hydraulic fluid within said inner support tube to flow in a direction to and from said outer support tube through said passageway means.
[0009] Still other objects, features, and attendant advantages of the present invention will become apparent to those skilled in the art from a reading of the following detailed description of embodiments constructed in accordance therewith, taken in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] The invention of the present application will now be described in more detail with reference to preferred embodiments of the apparatus and method, given only by way of example, and with reference to the accompanying drawings, in which:
[0011] [0011]FIG. 1A is a longitudinal cross-sectional view of a first preferred embodiment of the height adjustment mechanism of the present invention that can use any one of FIG. 2A, 2B, 2 D, or 2 F, depicting preferred embodiments of energy storage devices;
[0012] [0012]FIG. 1B is a longitudinal cross-sectional view of a second preferred embodiment of the height adjustment mechanism of the present invention;
[0013] [0013]FIG. 2A is a longitudinal cross-sectional view of a first embodiment of an energy storage device useful in the height adjustment mechanism of the present invention;
[0014] [0014]FIG. 2B is a longitudinal cross-sectional view of a second preferred embodiment of an energy storage device useful in the height adjustment mechanism of the present invention;
[0015] [0015]FIG. 2C is a partial view of the sealing means of the energy storage device in the circled area of FIG. 2B;
[0016] [0016]FIG. 2D is an exploded side view in partial section of a third embodiment of the energy storage device;
[0017] [0017]FIG. 2E is a side view of a fourth embodiment of the energy storage device prior to final assembly;
[0018] [0018]FIG. 2F is a longitudinal cross-sectional view depicting the fourth embodiment of the energy storage device of FIG. 2E in final assembly.
[0019] [0019]FIG. 3 is a cross-sectional side view of a third embodiment of the height adjustment mechanism of the present invention;
[0020] [0020]FIG. 4 is a longitudinal cross-sectional view of a fourth embodiment of the height adjustment mechanism of the present invention;
[0021] [0021]FIG. 5 is a longitudinal cross-sectional view of a fifth embodiment of the height adjustment mechanism of the present invention; and
[0022] [0022]FIG. 6 is a longitudinal cross-sectional view of an embodiment of a constant force spring of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0023] The improvements of the subject invention include improved reliability and consistency of performance, reduced manufacturing expense, elimination of critical leak paths, and improved preload capability. Revision of the fluid channel, valve and seal mechanisms to perform these tasks with a single element at a point internal to the outermost periphery of the unit serves to eliminate the leakage while improving the consistency of performance of the valve and reducing manufacturing costs.
[0024] The preload provided to the system by the system adjustment mechanism is important because when the adjustment mechanism is used in combination with a repositionable device such as a chair, for example, and the valve is open and the seat unloaded, the mechanism will rise to its upper position to be in a position for ready adjustment. In addition, the preload serves to increase the amount of energy stored by the descent of the loaded chair during adjustment. Several embodiments of improved means to achieve preload are taught by this disclosure. These embodiments chiefly entail some form of elastomeric bladder which can be inflated to a desired pressure to provide the desired preload. These bladders are inserted into a reservoir having rigid walls where the preload is achieved by the bladder(s) being compressed by the surrounding hydraulic fluid. These bladders can also be filled with a fluid that is in two phases (gas and liquid) at a desired pressure and temperature. This allows for the pressure to remain constant as the internal volume of the bladder changes, provided two phases are present. The constant pressure provides uniform fluid flow from the reservoir to the cylinder when the valve is open and no load is applied to the piston for extending the height adjustment mechanism to the maximum extended position. The constant pressure eliminates the potential problem of having too much pressure when the piston is at the bottom of the cylinder and too little pressure when the piston is extended to the top of the cylinder.
[0025] Another aspect of the invention is the provision of a constant force spring. The constant force spring works on the same principle as described above. A working fluid having gas and liquid phases at normal, or desired, operating temperatures and pressures exerts a constant pressure against a piston for the full range of motion of the piston within a cylinder. Provided the working fluid remains in a two phase state, the force against the piston will be constant for the full range of motion forming a constant force spring. Suitable working gases include, but are not limited to, HF 6 , 1,1,1,2-tetrafluoroethane, pentafluoroethane, difluoroethane, and 1,1,1-trifluoroethane, and preferably, but not necessarily, are non-toxic, nonflammable, and non-ozone depleting. When the piston compresses the gas phase of this fluid, the gas phase will be converted to liquid rather than increasing the internal pressure within the piston cylinder. The two phase fluid can be either a primary fluid or a secondary fluid used in conjunction with an incompressible liquid-phase fluid, such as hydraulic fluid. Such hydraulic fluids might include castor oil, glycerol and various glycols. In other applications, this constant force spring can provide a low stiffness mounting that will provide excellent vibration isolation, particularly at low frequency.
[0026] Referring to the drawing figures, like reference numerals designate identical or corresponding elements throughout the several figures.
[0027] A first preferred embodiment of the height adjustment mechanism of the present invention is shown in FIG. 1A, generally at 20 . Height adjustment mechanism 20 includes an outer support tube 22 which is closed on a first end 24 and open on a second end 26 and an inner support tube assembly 30 is telescopically received within and protruding from the second open end 26 of the outer support tube 22 . A sleeve 27 of self-lubricating bearing material is affixed within the open end 26 of outer support tube 22 . Inner tube assembly 30 includes an external tube 32 and an internal tube 34 disposed therein. External tube 32 and internal tube 34 are sealed and connected together at first ends 31 and 33 by first sealing and connecting means 36 . First sealing and connecting means 36 includes a spacer 38 , O-ring 39 , and elastomeric element 40 .
[0028] Elastomeric element 40 is a unitary member including sleeve portion 42 that fits over internal tube 34 ; a smaller diameter cylindrical portion 44 that receives a stem portion 52 of valve element 50 ; a thin, flexible portion 46 interconnecting sleeve 42 and cylindrical portion 44 which permits the valve element 50 to be moved between a first closed position (shown in FIG. 1A) in which valve 53 engages valve seat 51 and a second open position by means of a manually engageable valve actuator 54 , the first sealing and connecting means supporting the valve element 50 and biasing the closeable valve element 50 to its closed position. Valve actuator 54 has a cylindrical portion 56 which surrounds an upper end of cylindrical portion 44 .
[0029] External tube 32 and internal tube 34 are interconnected and sealed at second ends 35 and 37 , respectively, by a second connecting and sealing means 48 . This sealed area between external tube 32 and internal tube 34 includes a first annular shaped chamber 28 . In the FIG. 1A embodiment, sealing element 48 also captures the ends of a thin-walled elastomeric bladder 60 between itself and the external tube 32 and internal tube 34 . The interior 67 of bladder 60 can be inflated with a secondary fluid to a desired pressure level (e.g., between about 50 psi (345 kPa) and about 200 psi (1380 kPa)) through an opening (not shown) in sealing element 48 forming an energy storage device to provide a desired preload. The thin walled elastomeric bladder 60 can be any one of the preferred embodiments of energy storage devices of FIG. 2A, 2B, 2 D, or 2 F, inserted in place of bladder 60 in chamber 28 . Gases suitable as a secondary fluid include air, dry nitrogen, and carbon dioxide, depending on the choice of elastomeric material of bladder 60 . Examples of materials suitable for bladder 60 are natural rubber, nitrile, and butyl. If constant pressure is desired, the interior 67 of bladder 60 can be filled with a secondary fluid comprising a two phase fluid that is in the form of liquid and gas at the desired pressure and temperature. By way of example and not of limitation, a secondary fluid can be a two-phase fluid at a temperature of about 75° F. (24° C.) at a pressure of between about 50 psi (345 kPa) and about 150 psi (1035 kPa). The preload offsets the weight of the chair seat itself and provides a lifting force when the valve is opened to restore the chair seat to an upper most position for subsequent adjustment. By controlling the size of the opening between valve 53 and valve seat 51 , the chair operator can control the rate at which the operating fluid 69 passes through the valve and, hence, the rate of descent of the chair.
[0030] A piston rod assembly 62 is received within inner tube 34 , extends through second seal element 48 and is attached to outer support tube 22 at 61 . Piston rod assembly includes a housing 64 , a piston rod 66 , a piston head 68 and a cush 70 . A second chamber 58 is defined by inner tube 34 and piston assembly 62 . First chamber 28 and second chamber 58 are filled with an operating fluid 69 ; operating fluid 69 is preferably hydraulic fluid, and when valve 53 is opened, fluid can flow between first chamber 28 and second chamber 58 , depending on which chamber has the higher fluid pressure level. If the chair operator is not seated on the chair, the pressure in first chamber 28 will exceed the pressure in second chamber 58 because of the preload delivered by the energy storage device of bladder 60 . If the operator is seated, whether or not the seat has been extended to its upper position, but not at the minimum height, unseating valve 53 will cause fluid to flow from chamber 58 to chamber 28 as the chair is lowered under the operator's weight until the operator releases the valve actuator 54 or the minimum height is reached.
[0031] A second embodiment of the height adjustment mechanism of the present invention is shown in FIG. 1B, generally at 20 b . The second embodiment height adjustment mechanism 20 b includes many of the elements of the first embodiment height adjustment mechanism shown in FIG. 1A, and also includes bands 65 U, 65 L, bladder 60 a and chamber 28 a . In this embodiment, thin walled elastomeric bladder 60 a is attached around internal tube 34 by bands 65 U and 65 L. First chamber 28 a does not contain an operating fluid 69 but, rather, is pressurized by a secondary fluid, as described in FIG. 1A, forming an energy storage device to provide the desired preload, and when valve 53 is opened while the operator is seated, the fluid bulges bladder 60 a outwardly against the preload pressure in chamber 28 a , in effect, storing energy for later use. This embodiment functions equivalently to that of FIG. 1A above in that the preload provides a pressure imbalance between first chamber 28 (the space between bladder 60 a and internal tube 34 ) and second chamber 58 such that when the chair is not loaded and the valve is opened fluid flows in to second chamber 58 raising the level of the chair. The height of the chair is adjusted by the user sitting on the chair and releasing the valve until the desired height is achieved.
[0032] [0032]FIG. 2A depicts a first preferred embodiment of an energy storage device generally at 60 b . Storage device 60 b is a thin walled bladder that has been molded into a cylinder with a fill port 59 . Once bladder 60 b has been filled with a secondary fluid to the desired pressure, fill port 59 can be mechanically plugged or heat sealed. As with the previous embodiments, the cylindrical bladder 60 b is positioned in first chamber 28 directly in the operating fluid 69 to provide a preload to the operating fluid 69 .
[0033] [0033]FIGS. 2B and 2C depict a second preferred embodiment of a energy storage device generally at 60 c . Energy storage device 60 c includes a first inner elastomeric tube 72 and a second outer elastomeric tube 74 . The preferred materials for the inner elastomeric tube 72 and outer elastomeric tube 74 are natural rubber, nitrile, or butyl. A closure ring 76 closes off a first pair of ends 71 and 73 , respectively, of tubes 72 and 74 . A second closure ring 78 closes off a second pair of ends 75 and 77 , respectively, of tubes 72 and 74 (see FIG. 2C detail). The preferred materials for the closure rings are nylon, steel, or aluminum. The ends 71 and 73 are wrapped around closure ring 76 and ends 75 and 77 around closure ring 78 . An expandable plug or series of plugs 80 can be inserted into the slots in closure rings 76 and 78 and expanded like a rivet to lock them in place. Expandible plugs can take the form of metal double-walled, semi-annular ring segments, the lower extremity of the walls being deflectable outwardly to lock in the slots in closure rings 76 and 78 . Energy storage device 60 c can be inflated with a secondary fluid to the desired pressure through an opening 79 and then plugged by expandable plugs 80 . As with the previous embodiments, the energy storage device 60 c is positioned in first chamber 28 directly in the operating fluid 69 to provide a preload to the operating fluid 69 .
[0034] A third preferred embodiment of the energy storage device is shown in FIG. 2D generally at 60 d . Bladder 60 d comprises a cylindrical tube whose ends are sealed by closure members 84 and 86 . The preferred materials for the closure members 84 and 86 are nylon, steel, or aluminum. The bladder 60 d is preferably made from natural rubber, nitrile, or butyl. The extremities 81 and 82 are wrapped around members 84 and 86 and secured by expandable plugs 88 . Plug 88 is used to close off fill port 87 , as well as anchor end 84 of tube 60 d . Tube(s) 60 d can be pre-pressurized with a secondary fluid and as many tubes may be added to chamber 28 as are needed to provide the desired level of preload.
[0035] A fourth preferred embodiment of the energy storage device of the present invention is depicted in FIGS. 2E and 2F, generally at 60 e . In this embodiment bladder 60 e is formed as a molded tube having a first section 92 , a second section 94 , and a tapered transitional section 96 connecting the first and second sections. First section 92 is pulled through section 94 and, once the bladder 60 e is pressurized with a secondary fluid to a desired level to provide the desired preload, the two ends 91 , 93 can be bonded together and sealed, as shown in FIG. 2F. As with the previous embodiments, the cylindrical bladder 60 e is positioned in first chamber 28 directly in the operating fluid 69 to provide a preload to the operating fluid 69 . The preferred materials for the bladder are rubber, nitrile, and butyl.
[0036] [0036]FIG. 3 shows a third embodiment of the height adjustment mechanism of the present invention. While the thin walled bladder of earlier embodiments is preferred due to the material savings and the resultant reduced cost, the benefits of the present invention can be realized with conventional thick walled bladders 11 of the type used in U.S. Pat. No. 5,511,759. Simply adding an energy storage device from any of the embodiments of FIGS. 2 A- 2 E to that of FIG. 2D, shown here as 60 d of FIG. 2D, will provide the improved preload pressurization that this invention makes available.
[0037] Another aspect of the present invention is depicted in FIGS. 4 - 6 . In FIGS. 4 and 5, this aspect is shown as embodied as a pressurized accumulator in a device such as the inner tube assembly 30 of the chair height adjuster of FIG. 1A discussed above. In FIG. 4, operating fluid 69 is pumped between first chamber 28 and second chamber 58 by piston 66 , while a secondary fluid is captured between bladder 60 f and internal tube 34 forming interior space 67 creating an energy storage device. The secondary fluid is present as an equilibrium combination of both liquid and gaseous phases. The internal pressure of the interior space 67 is maintained at the vapor pressure of the gas as long as some liquid phase is present. Movement of piston 66 inward causes the gas to compress. However, rather than elevating the pressure, some of the gas is converted to liquid such that the internal pressure remains generally constant dependent on the secondary fluid temperature. Preferred secondary fluids include, but are not limited to, substitutes for Freon-12 such as: 1,1,1,2-tetrafluoroethane; pentafluoroethane; difluoroethane; and 1,1,1-trifluoroethane, all of which exhibit vapor pressures in the range of approximately 50 to 150 PSI (345 to 1035 kPa) for fluid temperatures in the range of 60-100° F. (16-38° C.). Thus, the force of the pressure of the secondary fluid against bladder 60 f is transferred to primary fluid 69 , maintaining a generally constant force against piston 66 and creating a generally constant force spring.
[0038] [0038]FIG. 5 depicts an alternate embodiment of the constant force spring of FIG. 4 in which the secondary fluid 90 is simply mixed with the operating fluid 69 . The differences in density will typically cause the secondary fluid 90 to float atop the operating fluid 69 whereby the space occupied by the secondary fluid 90 of chamber 28 acts as an energy storage device. Siphon tube 88 permits the denser primary working fluid 69 to move between first chamber 28 and second chamber 58 through the secondary fluid 90 floating atop the primary fluid 69 in first chamber 28 .
[0039] [0039]FIG. 6 applies the teachings of a constant force spring to a conventional piston cylinder 92 that can be utilized to isolate sensitive equipment such as electronic devices, from low frequency vibrations. The piston 66 in cylinder 92 has low mechanical stiffness and any vibrational movement of the equipment being protected will be dampened by the transition of the working fluid 90 between its gaseous and fluid phases, in lieu of creating a rise in internal pressure, forming a constant force spring. Air vent 97 is provided in bushing 95 so that air can flow to and from the chamber 98 formed by cylinder 92 , piston head 68 , and bushing 95 . The airflow permitted by air vent 97 prevents pressure fluctuations in chamber 98 that could reduce the effectiveness of the constant force spring. Piston head 68 has an O-ring seal 96 to prevent gas from escaping from the system. Even if a small amount of the gaseous phase escaped from the cylinder 92 , the fluid phase would replace it maintaining equilibrium pressure between the fluid and gas phases. Accordingly, the constant force spring of the subject invention will continue to function properly until the liquid phase of the secondary fluid 90 is depleted.
[0040] While the invention has been described in detail with reference to preferred embodiments thereof, it will be apparent to one skilled in the art that various changes can be made, and equivalents employed, without departing from the scope of the invention. | A chair height adjustment mechanism includes an energy storage unit which has a compressible fluid. This compressible fluid allows the compressible fluid displaced by the piston rod entering the cylinder, to store energy for subsequent use as the chair seat is raised. This fluid may be of the type that has a dual phase at room temperature such that increase in pressure on the compressible fluid causes a portion of that compressible fluid to transition from gaseous phase to liquid phase. This makes the energy storage unit a constant force spring. The features of this constant force spring may be used in a conventional piston cylinder, shock absorbing device, as well. | 0 |
FIELD OF THE INVENTION
[0001] This invention relates to a method of printing from an inkjet printhead, whilst modulating a peak power requirement for the printhead. It has been developed primarily to reduce the demands on a pagewidth printhead power supply, although other advantages of the methods of printing described herein will be apparent to the person skilled in the art.
CO-PENDING APPLICATIONS
[0002] The following applications have been filed by the Applicant simultaneously with the present application:
KPP001US KPP002US KPP003US KPP004US KPP006US KPP007US KPP008US CAG001US CAG002US CAG003US CAG004US CAG005US RKA001US RKA002US RKA003US RKA004US RKA005US RKA006US RKA007US RKA008US RKA009US RKB001US RKB002US RKB003US RKB004US RKB005US RKB006US RKC001US RKC002US RKC003US RKC004US RKC005US RKC006US RKC007US RKC008US RKC009US RKC010US RRD001US RRD002US RRD003US RRD004US RRD005US RRD006US RRD007US RRD008US RRD009US RRD010US RRD011US RRD012US RRD013US
The disclosures of these co-pending applications are incorporated herein by reference. The above applications have been identified by their filing docket number, which will be substituted with the corresponding application number, once assigned.
CROSS REFERENCE To RELATED APPLICATIONS
[0003] Various methods, systems and apparatus relating to the present invention are disclosed in the following US Patents/Patent Applications filed by the applicant or assignee of the present invention:
09/517539 6566858 09/112762 6331946 6246970 6442525 09/517384 09/505951 6374354 09/517608 6816968 10/203564 6757832 6334190 6745331 09/517541 10/203559 10/203560 10/636263 10/636283 10/866608 10/902889 10/902833 10/940653 10/942858 10/727181 10/727162 10/727163 10/727245 10/727204 10/727233 10/727280 10/727157 10/727178 10/727210 10/727257 10/727238 10/727251 10/727159 10/727180 10/727179 10/727192 10/727274 10/727164 10/727161 10/727198 10/727158 10/754536 10/754938 10/727227 10/727160 10/934720 11/212702 PEA31US 10/296522 6795215 10/296535 09/575109 6805419 6859289 09/607985 6398332 6394573 6622923 6747760 6921144 10/884881 10/943941 10/949294 11/039866 11/123011 11/123010 11/144769 11/148237 11/248435 11/248426 10/922846 10/922845 10/854521 10/854522 10/854488 10/854487 10/854503 10/854504 10/854509 10/854510 10/854496 10/854497 10/854495 10/854498 10/854511 10/854512 10/854525 10/854526 10/854516 10/854508 10/854507 10/854515 10/854506 10/854505 10/854493 10/854494 10/854489 10/854490 10/854492 10/854491 10/854528 10/854523 10/854527 10/854524 10/854520 10/854514 10/854519 10/854513 10/854499 10/854501 10/854500 10/854502 10/854518 10/854517 10/934628 11/212823 10/728804 10/728952 10/728806 10/728834 10/728790 10/728884 10/728970 10/728784 10/728783 10/728925 6962402 10/728803 10/728780 10/728779 10/773189 10/773204 10/773198 10/773199 6830318 10/773201 10/773191 10/773183 10/773195 10/773196 10/773186 10/773200 10/773185 10/773192 10/773197 10/773203 10/773187 10/773202 10/773188 10/773194 10/773193 10/773184 11/008118 11/060751 11/060805 11/188017 6623101 6406129 6505916 6457809 6550895 6457812 10/296434 6428133 6746105 10/407212 10/407207 10/683064 10/683041 6750901 6476863 6788336 11/097308 11/097309 11/097335 11/097299 11/097310 11/097213 11/210687 11/097212 11/212637 11/246687 11/246718 11/246685 11/246686 11/246703 11/246691 11/246711 11/246690 11/246712 11/246717 11/246709 11/246700 11/246701 11/246702 11/246668 11/246697 11/246698 11/246699 11/246675 11/246674 11/246667 11/246684 11/246672 11/246673 11/246683 11/246682 10/760272 10/760273 10/760187 10/760182 10/760188 10/760218 10/760217 10/760216 10/760233 10/760246 10/760212 10/760243 10/760201 10/760185 10/760253 10/760255 10/760209 10/760208 10/760194 10/760238 10/760234 10/760235 10/760183 10/760189 10/760262 10/760232 10/760231 10/760200 10/760190 10/760191 10/760227 10/760207 10/760181 10/815625 10/815624 10/815628 10/913375 10/913373 10/913374 10/913372 10/913377 10/913378 10/913380 10/913379 10/913376 10/913381 10/986402 11/172816 11/172815 11/172814 11/003786 11/003354 11/003616 11/003418 11/003334 11/003600 11/003404 11/003419 11/003700 11/003601 11/003618 11/003615 11/003337 11/003698 11/003420 11/003682 11/003699 11/071473 11/003463 11/003701 11/003683 11/003614 11/003702 11/003684 11/003619 11/003617 11/246676 11/246677 11/246678 11/246679 11/246680 11/246681 11/246714 11/246713 11/246689 11/246671 10/922842 10/922848 11/246704 11/246710 11/246688 11/246716 11/246715 11/246707 11/246706 11/246705 11/246708 11/246693 11/246692 11/246696 11/246695 11/246694 10/760254 10/760210 10/760202 10/760197 10/760198 10/760249 10/760263 10/760196 10/760247 10/760223 10/760264 10/760244 10/760245 10/760222 10/760248 10/760236 10/760192 10/760203 10/760204 10/760205 10/760206 10/760267 10/760270 10/760259 10/760271 10/760275 10/760274 10/760268 10/760184 10/760195 10/760186 10/760261 10/760258 11/014764 11/014763 11/014748 11/014747 11/014761 11/014760 11/014757 11/014714 11/014713 11/014762 11/014724 11/014723 11/014756 11/014736 11/014759 11/014758 11/014725 11/014739 11/014738 11/014737 11/014726 11/014745 11/014712 11/014715 11/014751 11/014735 11/014734 11/014719 11/014750 11/014749 11/014746 11/014769 11/014729 11/014743 11/014733 11/014754 11/014755 11/014765 11/014766 11/014740 11/014720 11/014753 11/014752 11/014744 11/014741 11/014768 11/014767 11/014718 11/014717 11/014716 11/014732 11/014742 11/097268 11/097185 11/097184 11/124202 11/124163 11/124157 11/124201 11/124167 11/228481 11/228477 11/228485 11/228483 11/228521 11/228517 09/575197 09/575195 09/575159 09/575132 09/575123 09/575148 09/575130 09/575165 09/575153 09/575118 09/575131 09/575116 09/575144 09/575139 09/575186 6681045 6728000 09/575145 09/575192 09/575181 09/575193 09/575156 09/575183 6789194 09/575150 6789191 6644642 6502614 6622999 6669385 6549935 09/575187 6727996 6591884 6439706 6760119 09/575198 6290349 6428155 6785016 09/575174 09/575163 6737591 09/575154 09/575129 09/575124 09/575188 09/575189 09/575162 09/575172 09/575170 09/575171 09/575161
[0004] An application has been listed by its docket number. This will be replaced when the application number is known. The disclosures of these applications and patents are incorporated herein by reference.
BACKGROUND TO THE INVENTION
[0005] Inkjet printers are now commonplace in homes and offices. For example, inkjet photographic printers, which print color images generated on digital cameras, are, to an increasing extent, replacing traditional development of photographic negatives. With the increasing use of inkjet printers, the demands of such printers in terms of print quality and speed, continue to increase.
[0006] All commercially available inkjet printers use a scanning printhead, which traverses across a stationary print medium. After each sweep of the printhead, the print medium incrementally advances ready for the next line(s) of printing. Such printers are inherently slow and are becoming unable to meet the needs of current demands of inkjet printers.
[0007] The present Applicant has previously described many different types of pagewidth printheads, which are fabricated using MEMS technology. In pagewidth printing, the print medium is continuously fed past a stationary printhead, thereby allowing high-speed printing at, for example, one page per 1-2 seconds. Moreover, MEMS fabrication of the printhead allows a much higher nozzle density than traditional scanning printheads, and print resolutions of 1600 dpi are possible.
[0008] Some of the Applicant's MEMS pagewidth printheads are described in the patents and patent applications listed in the cross-references section above, the contents of which are herein incorporated by reference.
[0009] To a large extent, pagewidth printing has been made possible by reducing the total energy required to fire each ink droplet and/or efficiently removing heat from the printhead via ejected ink. In these ways, self-cooling of the printhead can be achieved, which enables a pagewidth printhead having a high nozzle density to operate without overheating.
[0010] However, whilst a total amount of energy to print, say, a full-color photographic page will be approximately constant for any given pagewidth printhead, the power requirement of the printhead may, of course, vary. An average power requirement for printing a page is determined by the total energy required and the total time taken to print the page, assuming an equal distribution of printing over the time period. In addition, the power requirement of the printhead during printing of the page may fluctuate. Due to a particular configuration of the printhead or printer controller, some lines of print may consume more power than other lines of print. Hence, a peak power requirement for each line of printing may be different.
[0011] In a typical pagewidth printhead, nozzles ejecting the same color of ink are arranged longitudinally in color channels along the length of the printhead. Each color channel may comprise one or more rows of nozzles, all ejecting the same colored ink. In a simple example, there may be one cyan row of nozzles, one magenta row of nozzles and one yellow row of nozzles. Usually, each row of nozzles will be fired sequentially during printing e.g. cyan then magenta then yellow.
[0012] Furthermore, a typical pagewidth printhead may be comprised of a plurality of printhead modules, which abut each other and cooperate to form a printhead extending across a width of the page to be printed. Each printhead module is typically a printhead integrated circuit comprising nozzles and drive circuitry for firing the nozzles. The rows of nozzles extend over the plurality of printhead modules, with each printhead module including a respective segment of each nozzle row.
[0013] In previous patent applications, listed below, we described various types of printheads, printer controllers and methods of printing. The contents of these patent applications are herein incorporated by reference:
10/854521 10/854522 10/854488 10/854487 10/854503 10/854504 10/854509 10/854510 10/854496 10/854497 10/854495 10/854498 10/854511 10/854512 10/854525 10/854526 10/854516 10/854508 10/854507 10/854515 10/854506 10/854505 10/854493 10/854494 10/854489 10/854490 10/854492 10/854491 10/854528 10/854523 10/854527 10/854524 10/854520 10/854514 10/854519 10/854513 10/854499 10/854501 10/854500 10/854502 10/854518 10/854517 10/934628 11/212823
[0014] In our previous patent applications U.S. Ser. No. 10/854498 (Docket No. PLT012US), filed May 27, 2004, U.S. Ser. No. 10/854516 (Docket No. PLT017US), filed May 27, 2004 and U.S. Ser. No. 10/854508 (Docket No. PLT018US), filed May 27, 2004, we described a method of printing a line of dots where not all nozzles in one row or one segment are fired simultaneously. Rather, the nozzles are fired sequentially in firing groups in order to minimize the peak power requirement during printing of one line. As a consequence, each line of printing is typically not a perfectly straight line (unless the physical arrangements of the nozzles directly compensates for the firing order in which case it can be a straight line), although this imperfection is undetectable to the human eye. Each segment on a printhead module may comprise, for example, 10 firing groups of nozzles, in order to minimize, as far as possible within the print speed requirements, the peak power requirement for firing that segment of the nozzle row.
[0015] In our previous patent applications U.S. Ser. No. 10/854512 (Docket No. PLT014US), filed May 27, 2004 and U.S. Ser. No. 10/854491 (Docket No. PLT028US), filed May 27, 2004, we described a means for joining abutting printhead modules such that the effective distance between adjacent nozzles (‘nozzle pitch’) in the row remains constant. At one end of each printhead module, there is a displaced nozzle row portion, which is not aligned with its corresponding nozzle row. The firing of these displaced nozzles is timed so that they effectively print onto the same line as the row to which they correspond. As such, all references to “rows”, “rows of nozzles” or “nozzle rows” herein include nozzle rows comprising one or more displaced row portions, as described in U.S. Ser. No. 10/854512 (Docket No. PLT014US), filed May 27, 2004 and U.S. Ser. No. 10/854491 (Docket No. PLT028US), filed May 27, 2004.
[0016] In our previous patent applications U.S. Ser. No. 10/854507 (Docket No. PLT019US), filed May 27, 2004 and U.S. Ser. No. 10/854523 (Docket No. PLT030US), filed May 27, 2004, we described a means by which the visual effect of defective nozzles is reduced. The printhead described comprises one or more ‘redundant’ color channels, so that for a first row of nozzles ejecting a given color, there is a corresponding second (‘redundant’) row of nozzles from a different color channel which eject the same color. As described in U.S. Ser. No. 10/854507 (Docket No. PLT019US), filed May 27, 2004 and U.S. Ser. No. 10/854523 (Docket No. PLT030US), filed May 27, 2004, one line may be printed by the first nozzle row and the next line is printed by the second nozzle row so that the first and second nozzle rows print alternate lines on the page. Thus, if there are unknown defective nozzles in a given row, the visual effect on the page is halved, because only every other line is printed using that row of nozzles.
[0017] Alternatively, if there are known dead nozzles in a given row, the corresponding row of nozzles may be used to print dots in those positions where there is a known dead nozzle. In other words, only a small number of nozzles in the ‘redundant’ row may be used to print.
[0018] As already mentioned, the redundancy scheme described in U.S. Ser. No. 10/854507 (Docket No. PLT019US), filed May 27, 2004 and U.S. Ser. No. 10/854523 (Docket No. PLT030US), filed May 27, 2004 has the advantage of reducing the visual impact of dead nozzles, either known or unknown. Moreover, careful choice of redundant colors may be used to further reduce the visual impact of dead nozzles. For example, since yellow makes the lowest contribution (11%) to luminance, the human eye is least sensitive to missing yellow dots and, therefore, yellow would be a poor choice for a redundant color. On the other hand, black, makes a much higher contribution to luminance and would be a good choice for a redundant color.
[0019] However, while the redundancy scheme described in U.S. Ser. No. 10/854507 (Docket No. PLT019US), filed May 27, 2004 and U.S. Ser. No. 10/854523 (Docket No. PLT030US), filed May 27, 2004 can compensate for dead nozzles and reduce (e.g. halve) the number of dots fired by some nozzles, it places increased demands on the power supply which is used to power the printhead. The reason is because in the time it takes for the print medium to advance by one line (one ‘line-time’), each nozzle row must be allotted a portion of the line-time in which to fire, in order to achieve dot-on-dot printing and provide the desired image. Each nozzle row is allotted a portion of the line-time, since not all nozzle rows can fire simultaneously. (If all nozzle rows were to fire simultaneously, there would be an unacceptable current overload of the printhead).
[0020] In a simple CMY pagewidth printhead, having three rows of nozzles and no redundant color channels, each nozzle row must fire in one-third of the line-time. If the average power requirement of the printhead is x, then the peak power requirement over the duration of the line-time is as shown in Table 1:
TABLE 1 Color Peak Power Line-time Channel Requirement 1 C x 0.33 M x 0.67 Y x 0 (new line) C x . . . etc.
[0021] In this simple CMY printhead with no redundant nozzles, power is distributed evenly over the duration of the line-time so that the peak power requirement is constant and equal to the average power requirement of the printhead. From the standpoint of the power supply, this situation is optimal, but, on the other hand, there is no means for minimizing the visual effects of dead nozzles.
[0022] In a CMY printhead having redundant cyan and magenta color channels (ie. C1, C2, M1, M2 and Y color channels) and a pair of nozzle rows in each color channel (for even and odd dots), each nozzle row is allotted one-tenth of the line-time, since there are now ten nozzle rows. Now if the average power requirement of the printhead is x, with the redundancy scheme and firing sequence described in U.S. Ser. No. 10/854507 (Docket No. PLT019US), filed May 27, 2004 and U.S. Ser. No. 10/854523 (Docket No. PLT030US), filed May 27, 2004, the peak power requirement over the duration of two line-times is as shown in Table 2:
TABLE 2 Color Peak Power Line-time Channel Requirement 0 C1 (even) 1.67x 0.1 C2 (even) 0 0.2 M1 (even) 1.67x 0.3 M2 (even) 0 0.4 Y (even) 1.67x 0.5 C1 (odd) 1.67x 0.6 C2 (odd) 0 0.7 M1 (odd) 1.67x 0.8 M2 (odd) 0 0.9 Y (odd) 1.67x 0 (new line) C1 (even) 0 0.1 C2 (even) 1.67x 0.2 M1 (even) 0 0.3 M2 (even) 1.67x 0.4 Y (even) 1.67x 0.5 C1 (odd) 0 0.6 C2 (odd) 1.67x 0.7 M1 (odd) 0 0.8 M2 (odd) 1.67x 0.9 Y (odd) 1.67x 0 (new line) C1 (even) 1.67x . . . etc
[0023] It is evident from the above table that the peak power requirement of the printhead fluctuates severely between 1.67x and 0 within the period of a line-time, even though the average power consumed over the whole line-time is still x. In practical terms, it is difficult to manufacture a power supply which is able to deliver severely fluctuating amounts of power within each line-time. Hence, the redundancy described in U.S. Ser. No. 10/854507 (Docket No. PLT019US), filed May 27, 2004 and U.S. Ser. No. 10/854523 (Docket No. PLT030US), filed May 27, 2004 is difficult to implement in practice, even though it offers considerable advantages in terms of reducing the visual effects of known dead nozzles.
[0024] Of course, a printhead could be configured not to fire redundant color channels in a given line-time, resulting in an average of x peak power for each nozzle row. Such a configuration is effectively the same as that described in Table 1. While this configuration would address peak power and misdirectionality issues, it would not address the problem of known dead nozzles, since only one of each redundant color channel would be able to be fired in a given line-time, thereby losing one of the major advantages of redundancy.
[0025] It would be desirable to provide a method of printing whereby fluctuations in a peak power requirement are minimized. It would be further desirable to provide a method of printing whereby the average power requirement of the printhead is substantially equal to the peak power requirement at any given time during printing. It would be further desirable to provide a method of printing, whereby, in addition minimizing fluctuating peak power requirements, the visual effects of dead or malfunctioning nozzles are reduced. It would be further desirable to provide a method of printing, whereby, in addition to minimizing fluctuating peak power requirements, the visual effects of misdirected ink droplets is reduced.
SUMMARY OF THE INVENTION
[0026] In a first aspect, there is provided a method of modulating a peak power requirement of an inkjet printhead, said printhead comprising a plurality of first nozzles and a plurality of second nozzles supplied with a same colored ink, said first nozzles and second nozzles being configured in a plurality of sets, wherein each set of nozzles comprises one first nozzle and one corresponding second nozzle, each nozzle in a set being configurable to print a dot of said ink onto a substantially same position on a print medium, said method comprising:
[0027] (a) selecting a firing nozzle from at least one set of nozzles, said selection being on the basis of modulating said peak power requirement; and
[0028] (b) printing dots onto said print medium using said firing nozzle.
[0029] In a second aspect, there is provided a method of printing a line of dots from an inkjet printhead, said printhead comprising a plurality of first nozzles and a plurality of second nozzles supplied with a same colored ink, said first nozzles and second nozzles being configured in a plurality of sets, wherein each set of nozzles comprises one first nozzle and one corresponding second nozzle, each nozzle in a set being configurable to print a dot of said ink onto a substantially same position on a print medium,
[0030] said method comprising printing a line of dots across said print medium such that said first nozzles and said second nozzles each contribute dots to said line.
[0031] In a third aspect, there is provided a method of modulating a peak power requirement of an inkjet printhead, said printhead comprising a plurality of transversely aligned color channels, each color channel comprising at least one nozzle row extending longitudinally along said printhead, each nozzle in a color channel ejecting the same colored ink, wherein said printhead is comprised of a plurality of printhead modules, each printhead module comprising a respective segment of each nozzle row,
[0032] said method comprising each of said printhead modules firing a respective segment within a predetermined segment-time, wherein at least one of said fired segments is contained in a different color channel from at least one other of said fired segments.
[0033] In a fourth aspect, there is provided an inkjet printhead comprising a plurality of transversely aligned color channels, each color channel comprising at least one nozzle row extending longitudinally along said printhead, each nozzle in a row ejecting the same colored ink, wherein said printhead is comprised of a plurality of printhead modules, and the number of color channels is equal to the number of printhead modules.
[0034] In a fifth aspect, there is provided a printer controller for supplying dot data to an inkjet printhead, said printhead comprising a plurality of first nozzles and a plurality of second nozzles supplied with a same colored ink, said first nozzles and second nozzles being configured in a plurality of sets, wherein each set of nozzles comprises one first nozzle and one corresponding second-nozzle, each nozzle in a set being configurable by said printer controller to print a dot of said ink onto a substantially same position on a print medium, said printer controller being programmed to supply dot data such that said first nozzles and said second nozzles each contribute dots to a line of printing.
[0035] In a sixth aspect, there is provided a printer controller for supplying dot data to a printhead, said printhead comprising a plurality of transversely aligned color channels, each color channel comprising at least one nozzle row extending longitudinally along said printhead, each nozzle in a color channel ejecting the same colored ink, wherein said printhead is comprised of a plurality of printhead modules, each printhead module comprising a respective segment of each nozzle row, said printer controller being programmed to supply dot data such that each of said printhead modules fires a respective segment within a predetermined segment-time, wherein at least one of said fired segments is contained in a different color channel from at least one other of said fired segments.
[0036] In a seventh aspect of the invention, there is provided a printhead system comprising an inkjet printhead and a printer controller for supplying dot data to said printhead,
[0037] said printhead comprising a plurality of first nozzles and a plurality of second nozzles supplied with a same colored ink, said first nozzles and second nozzles being configured in a plurality of sets, wherein each set of nozzles comprises one first nozzle and one corresponding second nozzle, each nozzle in a set being configurable by said printer controller to print a dot of said ink onto a substantially same position on a print medium,
[0038] said printer controller being programmed to supply dot data such that said first nozzles and said second nozzles each contribute dots to a line of printing.
[0039] In an eighth aspect of the invention, there is provided a printhead system comprising an inkjet printhead and a printer controller for supplying dot data to said printhead,
[0040] said printhead comprising a plurality of transversely aligned color channels, each color channel comprising at least one nozzle row extending longitudinally along said printhead, each nozzle in a color channel ejecting the same colored ink, wherein said printhead is comprised of a plurality of printhead modules, each printhead module comprising a respective segment of each nozzle row,
[0041] said printer controller being programmed to supply dot data such that each of said printhead modules fires a respective segment within a predetermined segment-time, wherein at least one of said fired segments is contained in a different color channel from at least one other of said fired segments.
[0042] All aspects of the invention provide the advantage of modulating a peak power requirement of the inkjet printhead. The corollary is that a power supply, which supplies power to the printhead, need not be specially adapted to supply severely fluctuating amounts of power throughout each print cycle. In the present invention, the degree of peak power fluctuations within each line-time are substantially reduced. Hence, the design and manufacture of the printhead power supply may be simplified and the power supply is made more robust by virtue of not having to deliver severely fluctuating amounts of power to the printhead.
[0043] In addition to modulating the peak power requirement of the printhead, the present invention allows print quality to be improved by using redundant nozzle rows, and without compromising the above-mentioned improvements in peak power requirement. Print quality may be improved by, for example, reducing the visual effects of unknown dead nozzles in the printhead, and reducing the visual effects of misdirected ink droplets.
[0044] As used herein, the terms “row”, “rows of nozzles”, “nozzle row” etc. may include nozzle rows comprising one or more displaced row portions.
[0045] As used herein, the term “ink” includes any type of ejectable fluid, including, for example, IR inks and fixatives, as well as standard CMYK inks. Likewise, references to “same colored ink” include inks of a same color or type e.g. same cyan ink, same IR ink or same fixative.
[0046] As used herein, the term “substantially the same position on a print medium” is used to mean that a droplet of ink has an intended trajectory to print at a same position on the print medium (as another droplet of ink). However, due to inherent error margins in firing droplets of ink, random misdirects or persistent misdirects, a droplet of ink may not be printed exactly on its intended position on the print medium. Hence, the term “substantially the same position on a print medium” includes misplaced droplets, which are intended to print at the same position, but may not necessarily print at that position.
[0047] In accordance with some forms of the invention, the first nozzles and second nozzles are configured in a plurality of sets, wherein each set of nozzles comprises one first nozzle and one corresponding second nozzle. Further, each nozzle in a set is configurable to print a dot of ink onto a substantially same position on a print medium, so that the nozzles can be used interchangeably.
[0048] Optionally, a set is a pair of nozzles consisting of one first nozzle and one second nozzle. However, a set may alternatively comprise further (e.g. third and fourth) nozzles, with each nozzle in the set being configurable to print a dot of ink onto a substantially same position on a print medium. In other words, the present invention is not limited to two rows of redundant nozzles and may include, for example, three or more rows of redundant nozzles.
[0049] Preferably, the printhead is a stationary pagewidth printhead and the print medium is fed transversely past the printhead. The present invention has been developed primarily for use with such pagewidth printheads.
[0050] Optionally, the printhead comprises a plurality of transversely aligned color channels, each color channel comprising at least one nozzle row extending longitudinally along the printhead, each nozzle in a color channel ejecting the same colored ink. As described in more detail below, each transversely aligned color channel is allotted a portion of a line-time for firing. In this way, dot-on-dot printing can be achieved, which is optimal for dithering.
[0051] Color channels in the printhead may eject the same or different colored inks. However, all nozzles in the same color channel are typically supplied with and eject the same colored ink. Color channels ejecting the same colored ink are sometimes termed ‘redundant’ color channels. Typically, the printhead comprises at least one redundant color channel so that at least one color channel ejects the same colored ink as at least one other color channel.
[0052] Each color channel may comprise a plurality of nozzle rows. Optionally, each color channel comprises a pair of nozzle rows. Typically, nozzle rows in the same color channel are transversely offset from each other. For example, one nozzle row in a pair may be configured to print even dots on a line, while the other nozzle row in the pair may be configured to print odd dots on the same line. The nozzle rows in a pair are usually spaced apart in a transverse direction to allow convenient timing of nozzle firings. For example, the even and odd nozzle rows in one color channel may be spaced apart by two lines of printing.
[0053] Optionally, each set of nozzles comprises one first nozzle from a first color channel and one second nozzle from a second color channel. The first and second nozzles in the set are aligned transversely so that each can print onto the substantially same position on a print medium.
[0054] Optionally, one set of nozzles prints a column of same-colored dots down a print medium, with each nozzle in the set contributing dots to the column. As used herein, a “column” refers to a line of dots printed substantially perpendicular to the printhead and substantially parallel with a feed direction of the print medium. Optionally, one first nozzle in the set prints about half of the column and one second nozzle in the set prints about half of the column, so that the first and second nozzles in the set share printing of the column equally between them.
[0055] Optionally, a visual effect of misdirected ink droplets is reduced. An advantage of using a plurality (e.g. two) nozzles for printing the same column is that misdirected ink droplets may be averaged out between those nozzles.
[0056] Optionally, when printing a line of same-colored dots across the print medium, the first nozzles and second nozzles contribute dots to the line. As used herein, a “line” refers to a line of dots printed substantially parallel with the printhead and substantially perpendicular to a feed direction of the print medium. Optionally, the first nozzles print about half of the line and the second nozzles print about half of the line, so that the first and second nozzles share printing of the line equally between them. Accordingly, the peak power requirement for printing the line is reduced by about 50%, as compared to printing the line using only first nozzles or only second nozzles. Optionally, alternate first nozzles in a first nozzle row are used to print about half of the line and alternate second nozzles in a second nozzle row are used to print about half of the line. However, other patterns for sharing printing between the first and second nozzles may also be used.
[0057] Optionally, a visual effect of malfunctioning or dead nozzles is reduced. The nozzles may be known dead nozzles or unknown dead nozzles. The visual effect of an unknown dead nozzle is reduced by virtue of the fact that the nozzle is only required to print about half of the time. For example, with an unknown dead magenta nozzle, a column of magenta dots would be missing completely with no redundancy, whereas half of the column is still printed using redundancy. The latter is, of course, far more visually acceptable than the former.
[0058] Optionally, the color (which is the same color printed by the first and second nozzles) is magenta, cyan or black. The human eye is most sensitive to magenta, cyan and black, and these colors are consequently the preferred candidates for redundancy. A printhead may contain more than one redundant color channels. For example, the printhead may comprise first and second magenta nozzles, and first and second cyan nozzles.
[0059] In accordance with some forms of the invention, there is provided a method of out-of-phase printing so as to modulate a peak power requirement of the printhead. Typically, the printhead comprises a plurality of transversely aligned color channels with each color channel comprising at least one nozzle row extending longitiudinally along the printhead. Each nozzle in a color channel is supplied with and ejects the same colored ink. Typically, the printhead is comprised of a plurality of printhead modules, with each module comprising a respect segment of each nozzle row. Out-of-phase printing is provided by a method in which each of the printhead modules fires a respective segment within a predetermined segment-time, wherein at least one of the fired segments is contained in a different color channel from at least one other of the fired segments.
[0060] A segment-time may be defined as a predetermined fraction of one line-time. A line-time is defined as the time taken for the print medium to advance past the printhead by one line. Typically, all segments in a nozzle row are fired within one line-time. Optionally, a segment-time is equal to one line-time divided by the number of nozzle rows. However, a period of each line-time may be dedicated to a line-based overhead, in which case the segment-time will be less than one line-time divided by the number of nozzle rows. Generally, all segment-times are equal.
[0061] Optionally, at least one nozzle row has a different peak power requirement from other nozzle rows. For example, a redundant nozzle row would normally have half the peak power requirement of a non-redundant nozzle row. Optionally, a predetermined firing sequence modulates the peak power requirement during each segment-time so that the peak power requirement is within about 10%, optionally within 5%, of the average power requirement of the printhead. In some embodiments of the invention, the peak power requirement of the printhead is equal to the average power requirement of the printhead.
[0062] Typically, all segments on the printhead are fired within one-line time.
[0063] In some forms of the invention, the number of color channels is equal to the number of printhead modules. This is the optimum number of color channels and modules to achieve perfect out-of-phase firing. However, as will be explained in more detail below, the advantages of out-of-phase firing may still be achieved using any number of printhead modules and color channels.
[0064] Optionally, with equal numbers of modules and color channels, each of the printhead modules fires a segment from a different color channel within the predetermined segment-time. Further, each segment in a nozzle row may be fired sequentially. However, as will be explained in more detail below, each segment in a nozzle row need not be fired sequentially, whilst still enjoying the advantages of out-of-phase firing.
BRIEF DESCRIPTION OF THE DRAWINGS
[0065] Specific forms of the present invention will be now be described in detail, with reference to the following drawings, in which:
[0066] FIG. 1 is a plan view of a pagewidth printhead according to the invention;
[0067] FIG. 2 is a plan view of a printhead module, which is a part of the printhead shown in FIG. 1 ;
[0068] FIG. 3 is a schematic representation of a portion of each color channel of the printhead shown in FIG. 1 ;
[0069] FIG. 4A shows which even nozzles fire in one line-time using dot-at-a-time redundancy according to the invention;
[0070] FIG. 4B shows which odd nozzles fire in the next line-time from FIG. 4A ; and
[0071] FIG. 5 shows a printhead system according to the invention.
DETAILED DESCRIPTION OF THE INVENTION
[0072] The invention will be described with reference to a CMY pagewidth inkjet printhead 1 , as shown in FIG. 1 . The printhead 1 has five color channels 2 , 3 , 4 , 5 and 6 , which are C 1 , C 2 , M 1 , M 2 and Y respectively. In other words cyan and magenta have ‘redundant’ color channels. The reason for making C and M redundant is that Y only contributes 11% of luminance, while C contributes 30% and M contributes 59%. Since the human eye is least sensitive to yellow, it is more visually acceptable to have missing yellow dots than missing cyan or magenta dots. In this printhead, black (K) printing is achieved via process-black (CMY).
[0073] The printhead 1 is comprised of five abutting printhead modules 7 , which are referred to from left to right as A, B, C, D and E. The five modules 7 cooperate to form the printhead 1 , which extends across the width of a page (not shown) to be printed. In this example, each module 7 has a length of about 20 mm so that the five abutting modules form a 4″ printhead, suitable for pagewidth 4″×6″ color photo printing. During printing, paper is fed transversely past the printhead 1 and FIG. 1 shows this paper direction.
[0074] Each of the five color channels on the printhead 1 comprises a pair of nozzle rows. For example, the C 1 color channel 2 comprises nozzle rows 2 a and 2 b. These nozzle rows 2 a and 2 b extend longitudinally along the whole length of the printhead 1 . Where abutting printhead modules 7 are joined, there is a displaced (or dropped) triangle 8 of nozzle rows. These dropped triangles 8 allow printhead modules 7 to be joined, whilst effectively maintaining a constant nozzle pitch along each row. A timing device (not shown) is used to delay firing nozzles in the dropped triangles 8 , as appropriate. A more detailed explanation of the operation of the dropped triangle 8 is provided in the Applicant's patent applications U.S. Ser. No. 10/854512 (Docket No. PLT014US), filed May 27, 2004 and U.S. Ser. No. 10/854491 (Docket No. PLT028US), filed May 27, 2004.
[0075] Each of the printhead modules 7 contains a segment from each of the nozzle rows. For example, printhead module A contains segments 2 a A , 2 b A , 3 a A , 3 b A , 4 a A etc. Segments from the same nozzle row cooperate to form a complete nozzle row. For example, segments 2 a A , 2 a B , 2 a C , 2 a D and 2 a E cooperate to form nozzle row 2 a. FIG. 2 shows the printhead module A with its respect segments from each nozzle row.
[0076] Referring to FIG. 3 , there is shown a detailed schematic view of a portion of the five color channels 2 , 3 , 4 , 5 and 6 . From FIG. 3 , it can be seen that the pair of nozzle rows (e.g. 2 a and 2 b ) in each color channel (e.g. 2 ) are transversely offset from each other. In color channel 2 , for example, nozzle row 2 a prints even dots in a line, while nozzle row 2 b prints interstitial odd dots in a line.
[0077] Furthermore, the even rows of nozzles 2 a, 3 a, 4 a, 5 a and 6 a are transversely aligned, as are the odd rows of nozzles 2 b, 3 b, 4 b, 5 b and 6 b. This transverse alignment of the five color channels allows dot-on-dot printing, which is optimal in terms of dithering. Within a period of one line-time, all even nozzles and all odd nozzles must be fired so that dot-on-dot printing is achieved. The even and odd nozzles (e.g. 2 a and 2 b ) in the same color channel (e.g. 2 ) may be separated by, for example, two lines. Adjacent color channels (e.g. 2 and 3 ) may be separated by, for example, ten lines. However, it will be appreciated that the exact spacing between even/odd nozzle rows and adjacent color channels may be varied, whilst still achieving dot-on-dot printing.
[0000] Dot-At-A-Time Redundancy
[0078] In the printhead 1 described above, there are two cyan (C 1 , C 2 ) and two magenta (M 1 , M 2 ) color channels. In the Applicant's terminology, the C 1 /C 2 and M 1 /M 2 color channels are described as ‘redundant’ color channels.
[0079] As explained above, with five color channels and a pair of nozzle rows in each color channel, each nozzle row must print in one-tenth of the line-time in order to achieve all the advantages of redundancy and compensate for any known dead nozzles using a redundant color channel. The inherent power supply problems in relation to the redundancy scheme described in U.S. Ser. No. 10/854507 (Docket No. PLT019US), filed May 27, 2004 and U.S. Ser. No. 10/854523 (Docket No. PLT030US), filed May 27, 2004 have also been described above.
[0080] Dot-at-a-time redundancy is where redundant rows of nozzles are used such that there is never more than one out of every two adjacent nozzles firing within a single nozzle row. In other words, the even dots for a color are produced by two nozzle rows (each printing half of the even dots), and the odd dots for a color are produced by two nozzle rows (each printing half of the dots). For example, nozzle rows 2 a and 3 a may both contribute even dots to a line of printing, and nozzle rows 2 b and 3 b may both contribute odd dots to a line of printing.
[0081] FIGS. 4A and 4B show a firing sequence for two lines of printing using dot-at-a-time redundancy. The nozzles indicated in FIGS. 4A and 4B are not fired simultaneously; each nozzle row is allotted one-tenth of the line-time in which to fire its nozzles, with even nozzles rows firing sequentially followed by odd nozzle rows firing sequentially.
[0082] Referring to FIG. 4A , in the first line-time alternate nozzles are fired in each nozzle row from the C 1 , C 2 , M 1 and M 2 color channels. Nozzles fired from C 2 and M 2 complement those fired from C 1 and M For example, alternate even nozzles are fired from nozzle row 2 a and complementary alternate even nozzles are fired from nozzle row 3 a. Nozzle rows 6 a and 6 b in the Y channel have no redundancy and each of these nozzle rows must therefore fire all its nozzles in one-tenth of the line-time.
[0083] Referring to FIG. 4B , in the second line-time the alternate nozzles fired in the first line-time are inversed.
[0084] By using this dot-at-a-time redundancy scheme, print quality is improved by reducing misdirection artifacts (thereby maximizing dot-on-dot placement) and reducing the visual effect of unknown dead nozzles. For example, if half of the dots in a column are from an operational nozzle and half are from a dead nozzle, the visual effect of the dead nozzle will be reduced and the effective print quality is greater than if the entire column came from the dead nozzle. In other words, the present invention achieves at least as good print quality as the line-at-a-time redundancy described in U.S. Ser. No. 10/854507 (Docket No. PLT019US), filed May 27, 2004 and U.S. Ser. No. 10/854523 (Docket No. PLT030US), filed May 27, 2004.
[0085] Moreover, the peak power requirements of the printhead are modulated during printing of each line, so that the peak power requirements do not fluctuate as severely as in Table 2. Table 3 shows how the peak power requirement of the printhead (having an average power requirement of x) varies over two lines of printing using dot-at-a-time redundancy according to the present invention:
TABLE 3 Color Nozzle Peak Power Line-time Channel Row Reqnirement 0 2 (C1) 2a (even) 0.83x 0.1 3 (C2) 3a (even) 0.83x 0.2 4 (M1) 4a (even) 0.83x 0.3 5 (M2) 5a (even) 0.83x 0.4 6 (Y) 6a (even) 1.67x 0.5 2 (C1) 2b (odd) 0.83x 0.6 3 (C2) 3b (odd) 0.83x 0.7 4 (M1) 4b (odd) 0.83x 0.8 5 (M2) 5b (odd) 0.83x 0.9 6 (Y) 6b (odd) 1.67x 0 (new line) 2 (C1) 2a (even) 0.83x 0.1 3 (C2) 3a (even) 0.83x 0.2 4 (M1) 4a (even) 0.83x 0.3 5 (M2) 5a (even) 0.83x 0.4 6 (Y) 6a (even) 1.67x 0.5 2 (C1) 2b (odd) 0.83x 0.6 3 (C2) 3b (odd) 0.83x 0.7 4 (M1) 4b (odd) 0.83x 0.8 5 (M2) 5b (odd) 0.83x 0.9 6 (Y) 6b (odd) 1.67x 0 (new line) 2 (C1) 2a (even) 0.83x . . . etc
[0086] It is evident from Table 3 that the fluctuations in peak power requirement are fewer and less severe compared to line-at-a-time redundancy, described in Table 2. In terms of the design of the printhead power supply, dot-at-a-time redundancy according to the present invention offers significant advantages over line-at-a-time redundancy, whilst maintaining the same improvements in print quality.
[0000] Out-Of-Phase Firing
[0087] In all the firing sequences described so far, each color channel is fired in-phase - that is, a whole row of, say, even nozzles from one color channel is fired within its allotted portion of the line-time. In-phase firing provides simpler programming of the printer controller, which controls the firing sequence via dot data sent to the printhead 1 .
[0088] However, according to another form of the present invention, the firing may be out-of-phase—that is, within the same allotted portion of the line-time (termed the ‘segment-time’), at least one segment of nozzles is fired from a color channel that is different from at least one other segment of nozzles. With appropriate sequencing of segment firings, a whole nozzle row can be fired within one line-time, such that the net result is effectively the same as in-phase firing.
[0089] In the case of the printhead 1 , having five color channels and five segments in each nozzle row, it possible to fire segments from all different color channels within one segment time (i.e. one-tenth of a line-time). Segments contained in the same nozzle row are, therefore, fired sequentially during one line-time.
[0090] A major advantage of out-of-phase firing is that if one or more color channels (e.g. Y) has a different peak power requirement to the other color channels, this difference is averaged into the power requirements of the other color channels within each segment-time. Hence, the spike in power (corresponding to the Y channel) in Table 3 is effectively merged into rest of the line-time. The result is that the peak power requirement during each segment-time is always equal to the average power requirement for the printhead. This situation is optimal for supplying power to the printhead.
[0091] Table 4 illustrates a sequence of out-of-phase firing for one line of printing from the printhead 1 , using dot-at-a-time redundancy.
TABLE 4 Line- Module A Module B Module C Module D Module E Peak Power time (CC, S, P) (CC, S, P) (CC, S, P) (CC, S, P) (CC, S, P) Requirement 0 C1, 2a A , C2, 3a B , M1, 4a C , M2, 5a D , Y, 6a E , x 0.83x 0.83x 0.83x 0.83x 1.67x 0.1 C2, 3a A , M1, 4a B , M2, 5a C , Y, 6a D , C1, 2a E , x 0.83x 0.83x 0.83x 1.67x 0.83x 0.2 M1, 4a A , M2, 5a B , Y, 6a C , C1, 2a D , C2, 3a E , x 0.83x 0.83x 1.67x 0.83x 0.83x 0.3 M2, 5a A , Y, 6a B , C1, 2a C , C2, 3a D , M1, 4a E , x 0.83x 1.67x 0.83x 0.83x 0.83x 0.4 Y, 6a A , C1, 2a B , C2, 3a C , M1, 4a D , M2, 5a E , x 1.67x 0.83x 0.83x 0.83x 0.83x 0.5 C1, 2b A , C2, 3b B , M1, 4b C , M2, 5b D , Y, 6b E , x 0.83x 0.83x 0.83x 0.83x 1.67x 0.6 C2, 3b A , M1, 4b B , M2, 5b C , Y, 6b D , C1, 2b E , x 0.83x 0.83x 0.83x 1.67x 0.83x 0.7 M1, 4b A , M2, 5b B , Y, 6b C , C1, 2b D , C2, 3b E , x 0.83x 0.83x 1.67x 0.83x 0.83x 0.8 M2, 5b A , Y, 6b B , C1, 2b C , C2, 3b D , M1, 4b E , x 0.83x 1.67x 0.83x 0.83x 0.83x 0.9 Y, 6b A , C1, 2b B , C2, 3b C , M1, 4b D , M2, 5b E , x 1.67x 0.83x 0.83x 0.83x 0.83x 0 (new C1, 2a A , C2, 3a B , M1, 4a C , M2, 5a D , Y, 6a E , x line) 0.83x 0.83x 0.83x 0.83x 1.67x ... etc CC = Color Channel; S = Segment; P = Peak Power Requirement
[0092] It should be remembered that, even within one segment, not all nozzles fire simultaneously. The nozzles in one segment are arranged in firing groups, which fire sequentially over the course of their allotted segmnent-time. However, the important point is that at any given instant, some C 1 , C 2 , M 1 , M 2 and Y nozzles will fire simultaneously, thereby averaging out the higher peak power requirement of the yellow nozzle row.
[0093] In the case of five printhead modules and five color channels, it can be seen that out-of-phase firing works out well. Segments from each color channel can be rotated so that all different segments are fired in one segment-time.
[0094] However, it will be appreciated that out-of-phase firing also works well with any number of printhead modules or color channels. For example, using 20 mm printhead modules 7 , an A4 pagewidth printhead is comprised of eleven abutting modules [(i) to (xi)]. With five color channels and eleven printhead modules, it is impossible to ensure that each printhead module fires a different color channel within a segment-time (i.e. one-tenth of a line-time). Regardless, out-of-phase firing can still be used to optimize the peak power requirement of the printhead.
[0095] For example, the A 4 pagewidth printhead may have C, M, Y, K1 and K2 color channels. Since there are redundant K channels, these nozzle rows will have a lower peak power requirement than the C, M and Y channels using dot-at-a-time redundancy. Using in-phase firing, there would be appreciable peak power fluctuations during each line-time (C=1.25x, M=1.25x, Y=1.25x, K1=0.625x, K2=0.625x).
[0096] However, it can be seen from Table 5 that out-of-phase firing accommodates the eleven printhead modules and provides a peak power requirement that is always within 10% of the average power requirement x of the printhead. Indeed, the peak power requirement is always within 5% of the average power requirement x in this example. For the purposes of providing a power supply for the printhead, such small variations in peak power requirement during each line-time are not significant and would not affect the design of the power supply.
TABLE 5 t (i) (ii) (iii) (iv) (v) (vi) (vii) (viii) (ix) (x) (xi) P 0 C(e) M(e) Y(e) K1(e) K2(e) C(e) M(e) Y(e) K1(e) K2(e) C(e) 1.023x 0.1 M(e) Y(e) K1(e) K2(e) C(e) M(e) Y(e) K1(e) K2(e) C(e) M(e) 1.023x 0.2 Y(e) K1(e) K2(e) C(e) M(e) Y(e) K1(e) K2(e) C(e) M(e) Y(e) 1.023x 0.3 K1(e) K2(e) C(e) M(e) Y(e) K1(e) K2(e) C(e) M(e) Y(e) K1(e) 0.966x 0.4 K2(e) C(e) M(e) Y(e) K1(e) K2(e) C(e) M(e) Y(e) K1(e) K2(e) 0.966x 0.5 C(o) M(o) Y(o) K1(o) K2(o) C(o) M(o) Y(o) K1(o) K2(o) C(o) 1.023x 0.6 M(o) Y(o) K1(o) K2(o) C(o) M(o) Y(o) K1(o) K2(o) C(o) M(o) 1.023x 0.7 Y(o) K1(o) K2(o) C(o) M(o) Y(o) K1(o) K2(o) C(o) M(o) Y(o) 1.023x 0.8 K1(o) K2(o) C(o) M(o) Y(o) K1(o) K2(o) C(o) M(o) Y(o) K1(o) 0.966x 0.9 K2(o) C(o) M(o) Y(o) K1(o) K2(o) C(o) M(o) Y(o) K1(o) K2(o) 0.966x 0 C(o) M(o) Y(o) K1(o) K2(o) C(o) M(o) Y(o) K1(o) K2(o) C(o) 1.023x t = line-time; P = Peak Power Requirement (e) = even rows of nozzles; (o) = odd rows of nozzles
[0097] From the foregoing it will be appreciated that the combination of out-of-phase firing together with dot-at-a-time redundancy is optimal for achieving excellent print quality and an acceptable power requirement for the printhead during printing.
[0098] However, these methods of printing may equally be used individually, providing their inherent advantages, or in combination with other methods of printing. For example, out-of-phase firing or dot-at-a-time redundancy may be used in combination with printhead module misplacement correction and/or dead nozzle compensation, as described in our earlier patent applications U.S. Ser. No. 10/854521 (Docket No. PLT001US) filed May 27, 2004 and U.S. Ser. No. 10/854515 (Docket No. PLT020US), filed May 27, 2004.
[0000] Printer Controller
[0099] It will also be appreciated by the skilled person that a printer controller 10 , shown schematically in FIG. 5 , may be suitably programmed to provide dot data to the printhead 1 , so as to print in accordance with the methods described above. A printhead system 20 comprises the printer controller 10 and the printhead 1 , which is controlled by the controller. The printer controller 10 communicates dot data to the printhead 1 for printing.
[0100] A suitable type of printer controller, which may be programmed accordingly, was described in our earlier patent application U.S. Ser. No. 10/854521 (Docket No. PLT001US) filed May 27, 2004.
[0101] It will, of course, be appreciated that the present invention has been described purely by way of example and that modifications of detail may be made within the scope of the invention, which is defined by the accompanying claims. | A printer controller for supplying dot data to an inkjet printhead is provided. The printhead comprises a plurality of first nozzles and a plurality of second nozzles supplied with a same colored ink. The first nozzles and second nozzles are configured in a plurality of sets, wherein each set of nozzles comprises one first nozzle and one corresponding second nozzle. Each nozzle in a set is configurable by the printer controller to print a dot of the ink onto a substantially same position on a print medium. The printer controller is programmed to supply dot data such that the first nozzles and the second nozzles each contribute dots to a line of printing. | 1 |
[0001] This application claims priority to 60/685,449, filed May 26, 2005, the entire contents of which are incorporated herein by reference. Without limiting the scope of the invention, its, background is described in connection with Carbon nanotubes (CNTs).
STATEMENT OF FEDERAL GOVERNMENT SUPPORT
[0002] This invention was made with U.S. Government support under a Contract awarded by the MIRROR Federal Initiative. The government may own certain rights in this invention.
TECHNICAL FIELD OF THE INVENTION
[0003] The present invention relates in general to the field of nanotechnology and, more particularly, to compositions and methods for the isolation and manipulation of nanomaterials using diameter-selective reversible closable peptides.
BACKGROUND OF THE INVENTION
[0004] Carbon nanotubes have novel electrical and mechanical properties with potential biological applications ranging from sensors to tissue supports to artificial muscles (1). Various agents, e.g., surfactants (ref. 2 and references therein), polymers (refs 3 and 4, and references therein), polypeptides (5, 6 and references therein), and nucleic acids (7, 8)) have been used to disperse CNTs, however, two major hurdles exist that limit the usefulness of CNTs in many applications. First, current preparative methods for CNTs generate heterogeneous nanotube mixtures that can vary in length, diameter and electronic type (semiconducting, semimetallic and metallic). This heterogeneity ultimately limits the utility of the CNT materials. Recent work on the length (4, 9-13), diameter (7, 8, 14) and concomitant length and diameter (15) separation of CNTs, however, has provided important advances in the area of nanotube purification. Second, unmodified CNTs are very hydrophobic, readily aggregate, and are therefore difficult to interface with biological materials. Detergents like sodium dodecyl sulfate (SDS) that are commonly used to solubilize CNTs in water would likely disrupt cellular membranes and are incompatible with many biological applications, while covalent modification of CNTs with soluble moieties (16, 17) interferes with CNT properties.
[0005] What are needed are compositions and methods for the isolation, separation, characterization and functionalization of CNTs. These compositions and methods must be highly selective, rapid and inexpensive. Furthermore, the compositions and methods should be made from easily available materials that are not harmful to the environment. In fact, in some cases it will be very useful to use these compositions and methods to isolate and even chelate CNTs.
SUMMARY OF THE INVENTION
[0006] The present invention includes compositions and methods for making and using a cyclic peptide that binds specifically a single-walled carbon nanotube. The peptide may be reversibly or even irreversibly cyclized. One example of a closable peptide is an amphiphilic peptide, which may include alternating L- and D-amino acids. Alternatively, the peptide may include, e.g., typical amino acid monomer building blocks and/or mixtures and combinations of amino acids and other building blocks (e.g., alpha-hydroxy acids) that yield non-traditional peptide backbones when assembled together (e.g., peptidomimetics). The peptide may even include non-native amino acids, that is, amino acids that have non-natural side chains, including modified side chains or even side chains that are modified post-translationally or post-synthesis. Therefore, the peptides may be chemically synthesized in whole or in part by chemical synthesis and/or may be synthesized in whole or in part by using ribosomes in vivo or in vitro.
[0007] The cyclizable peptide may include two or more terminal groups that can form covalent or noncovalent linkage(s) within the peptide to create a closed ring structure. One example of a cyclizable peptide may include both N- and C-termini that are derivatized with thiol groups. Alternatively, the peptide may have the N-terminus as a free amine and the C-terminus as a free acid group such that they can form an amide bond and close the ring. The peptide may be used to solubilize carbon single-walled nanotubes.
[0008] The cyclic peptide may be cyclized in a reversible manner by reducing and oxidizing thiol groups that are at the ends of the peptide and/or internal to the peptide. In fact, the same peptide may be cyclized at multiple locations by providing thiol groups either in side chains and/or at the N- and/or the C-end. One example of a peptide has the sequence: R 1 —Y( D AK) 4 D AQ-NH—R 2 , wherein R 1 and R 2 comprise thiol or other groups. Another example of a peptide has the sequence: R 1 —Y( D AK) 6 D AQ-NH—R 2 , wherein R 1 and R 2 comprise thiol or other groups.
[0009] Yet another example of the present invention includes a carbon nanotube separating agent that is an amphiphilic helical peptide that specifically binds a single-walled carbon nanotube. The peptide noncovalently binds the single-walled carbon nanotube and may further include a substrate to which the peptides are attached, e.g., a glass, a quartz, a silicon, a bead, a gel, a polymer, a column and the like. For example, the peptides may themselves be crosslinked to form a polymer. The peptides may also include one or more sidegroups that are derivatized for crosslinking. In one example, the reversible cyclic peptide includes alternating L- and D-amino acids with N- and C-termini derivatized thiol groups.
[0010] The present invention also includes a method of capturing single-walled carbon nanotubes by mixing single-walled carbon nanotubes with one or more cyclized peptide comprising at least two thiol groups. Examples of peptide for use with the method of the present invention include, e.g., a peptide named RC5: R 1 —Y( D AK) 4 D AQ-NH—R 2 (SEQ ID NO.: 1); and/or RC7: R 1 —Y( D AK) 6 D AQ-NH—R 2 (SEQ ID NO.: 2).
[0011] Other examples of the present invention include: a single-walled carbon nanotube purified by diameter selection using a cyclized peptide with at least two thiol groups. A single-walled carbon nanotube purification system may include a substrate with one or more cyclized peptides that bind specifically and non-covalently to a single-walled carbon nanotube having a specific diameter. Examples of substrates include: a bead, a gel, a polymer, a glass, a quartz, a silicon, a ceramic, a plastic, a protein, a nucleic acid, a carbohydrate, a lipid and mixtures and combinations thereof.
[0012] The present invention may also include one or more of the following: (1) a closable peptide with at least two thiol groups, wherein the peptide binds single-walled carbon nanotubes; (2) a carbon nanotube separating agent that has an amphiphilic closable peptide that binds specifically a single-walled carbon nanotube; (3) a chelating agent with a cyclizable peptide that binds nanotubes non-covalently; and/or (4) a closable peptide that binds nanostructures of a predetermined size.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] For a more complete understanding of the features and advantages of the present invention, reference is now made to the detailed description of the invention along with the accompanying figures and in which:
[0014] FIG. 1A (top) is a model (end-on view) of RC5 with a (11,3) SWNT (C, green; H, white; N, blue; O, red; S, yellow; SWNT, pink) and FIG. 1B shows the RC5 and RC7 sequences;
[0015] FIG. 2 is a graph that shows the percent reduced RC7 (Left axis, red solid line) in dispersion as a function of sonication time (measured by Ellman test) and on the Right axis, blue dotted line, the A 375 for RC7/SWNT dispersion as a function of sonication time;
[0016] FIG. 3 shows the oxidation state of: (Tube 1) RC5 initially oxidized (cyclized), sonicated in presence of SWNTs; (Tube 2) RC5 initially reduced (linear), oxidized in presence of SWNTs; (Tube 3) RC7 initially oxidized (cyclized), sonicated in presence of SWNTs; (Tube 4) RC7 initially reduced (linear), oxidized in presence of SWNTs;
[0017] FIG. 4 is a graph that shows the UV/Vis/NIR spectra of RC5/SWNT (red, lower spectrum) and RC7/SWNT (blue, upper spectrum) dispersions;
[0018] FIGS. 5A to 5 D are graphs of ( 5 A and 5 B) Raman RBM regions of RC5/SWNT ( 5 A) and RC7/SWNT ( 5 B) dispersions (red, 16 k×g, 20 min; blue, 100 k×g, 1 hr; 633 nm excitation); FIGS. 5C and 5D are comparisons of RBM regions of RC5/SWNT (red) and RC7/SWNT (blue) dispersions excited at 633 nm ( 5 C) and 488 nm ( 5 D);
[0019] FIG. 6 is a graph of the Raman RBM regions of SDS/SWNT dispersion (red, 16 k×g, 20 min; blue, 100 k×g, 1 hr; 633 nm excitation);
[0020] FIG. 7A shows the expected dimensions for RC5/SWNT and RC7/SWNT structures. FIGS. 7B and 7C are 1.0×1.0 μm AFM images of diluted 100 k×g RC5/SWNT ( 7 B) and RC7/SWNT ( 7 C) dispersions. FIG. 7D (left) is an AFM height profile taken along the length of a single nanotube ( 7 D, right AFM image, 0.5×0.5 μm), showing the differences between the smooth and beaded areas (beaded areas indicated by arrows). FIG. 7E shows the measured diameter distributions (smooth regions) for diluted 100 k×g RC5/SWNT and RC7/SWNT dispersions (n=100; four 2.0×2.0 μm images, two samples for each peptide); and
[0021] FIG. 8 shows two models showing possible polymerization of RCPs around SWNTs (C, green; H, white; N, blue; O, red; S, yellow; SWNT, pink);
DETAILED DESCRIPTION OF THE INVENTION
[0022] While the making and using of various embodiments of the present invention are discussed in detail below, it should be appreciated that the present invention provides many applicable inventive concepts that can be embodied in a wide variety of specific contexts. The specific embodiments discussed herein are merely illustrative of specific ways to make and use the invention and do not delimit the scope of the invention.
[0023] To facilitate the understanding of this invention, a number of terms are defined below. Terms defined herein have meanings as commonly understood by a person of ordinary skill in the areas relevant to the present invention. Terms such as “a”, “an” and “the” are not intended to refer to only a singular entity, but include the general class of which a specific example may be used for illustration. The terminology herein is used to describe specific embodiments of the invention, but their usage does not delimit the invention, except as outlined in the claims.
[0024] Reversible cyclic peptides (RCPs) with alternating L- and D-amino acids with N- and C-termini derivatized with thiol-containing groups allowing reversible peptide cyclization—to solubilize and noncovalently functionalize carbon single-walled nanotubes (SWNTs) in aqueous solution. Solubilization occurs through wrapping of RCPs around the circumference of a SWNT, followed by the formation of head-to-tail covalent bonds, yielding closed rings on the nanotubes. By controlling the length of the RCPs limited diameter-selective solubilization of the SWNTs was demonstrated as revealed by UV/Vis/NIR and Raman spectroscopies, as well as atomic force microscopy.
[0025] To improve CNT solubility in water and biocompatibility, a family of amphiphilic helical peptides was developed that noncovalently bind and solubilize single-walled carbon nanotubes (SWNTs) in water, yielding unbundled, individual SWNTs (5, 18). Although these helical peptides are excellent solubilization agents, there are two peptide properties that we would like to improve: (1) their affinity for CNTs, and (2) the selectivity of CNT solubilization, based either on nanotube type or size. The class of peptides described herein may covalently close around the circumference of CNTs. Encircling CNTs with peptides has two major advantages. One is that the peptides will not dissociate from the CNTs, so they provide extremely stable CNT dispersions. The second is that CNTs can be preferentially solubilized when the nanotube diameter is small enough to be encircled by a given length peptide, thereby enabling diameter-selective separation of SWNTs.
[0026] One example of the novel class of peptides are cyclic peptides containing alternating L- and D-amino acids (AAs) (19, 20) called reversible cyclic peptides (RCPs)(21) for the diameter-selective solubilization of HiPco SWNTs ( FIG. 1A ). In L/D-peptides, all side chains reside on one face of the backbone, encouraging a ring-like conformation with the side chains on the ring exterior. In addition, our cyclic peptides have N- and C-termini that are derivatized to contain thiol groups, allowing reversible peptide cyclization through a disulfide bond ( FIG. 1A ). These results demonstrate that peptides with different N-to-C-terminal lengths wrap around SWNTs have sufficiently small diameters to cause selective enrichment of small diameter CNTs dispersed in solution.
[0027] Peptide Design. Computer-aided modeling used the software packages InsightII and Discover (Accelrys Inc.; San Diego, Calif.). The diameter distribution for the HiPco SWNTs used for these studies was previously reported to be 0.7 to 1.4 nm (22). To determine the appropriate RCP ring sizes that would selectively encircle CNTs in the 0.7 to 1.4 nm range, model (11, 3) and (14, 5) SWNT structures with diameters of 1.01 and 1.35 nm, respectively, were created from atomic coordinates obtained from http://www.pa.msu.edu/cmp/csc/nanotube.html. When the van der Waals radii are taken into account, the SWNT diameters are 1.15 and 1.49 nm, respectively. Diameters including van der Waals radii were used to design RCPs of lengths that, when closed into rings, would form pores capable of selectively encircling CNTs of different diameters ( FIG. 1 ). The RCPs were generated using backbone dihedral angles reported previously for standard cyclic peptides (23).
[0028] Peptide/CNT Solution Preparation. The peptides RC5 and RC7 were synthesized and purified following previously published methods (21). Unpurified SWNTs, produced by the method of high-pressure disproportionation of carbon monoxide (HiPco process), were obtained from Carbon Nanotechnologies, Inc., and used without modification. Ultra pure deionized (DI) water was degassed under high vacuum and heating to remove dissolved oxygen that would promote disulfide bond formation in peptide solutions. Degassed DI water was used to prepare all solutions. The concentrations of RCP stock solutions were determined by UV absorbance spectroscopy utilizing the absorbance of the tyrosine residue in each RCP (ε=1420 M −1 cm −1 at 275 nm). The concentration of free thiol in solution was determined by reacting an aliquot of peptide solution with 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB) in 0.1 M sodium phosphate buffer, pH 8 (Ellman test (24)), and comparing the resulting A410 (ε=13650 M-1 cm-1) to a reference solution. The Ellman test was used to determine the free thiol concentration of stock solutions as well as to monitor the oxidation of experimental solutions.
[0029] Peptide/SWNT dispersions were prepared by sonicating 1 mL of solution containing HiPco SWNTs (˜30 μg) and peptide at a desired concentration. Sonication was performed for specified times using a VWR Scientific Branson Sonifier 250 horn sonicator with a 5 Watt input energy to the solutions. The dispersions were then centrifuged, and the supernatant was used for all analyses.
[0030] UV/is/NIR Spectroscopy. RCP/SWNT dispersions were prepared as described above, with the exception that D 2 O was used instead of H 2 O. Absorption spectra were obtained using a Perkin-Elmer Lamda 900 UV-Vis-NIR spectrophotometer and quartz cells having a 1 cm path length. Spectra were collected every nm between 200 and 1600 nm.
[0031] Raman Spectroscopy. Samples for Raman analysis were prepared as follows. A 100 μM peptide solution was vortexed with two equivalents of tris(2-carboxyethyl)-phosphine HCl (TCEP; Pierce Biotechnology, Inc.; Rockford, Ill.) for 10 min prior to sonication with. HiPco SWNTs. Centrifugation was then carried out in the following sequence: a first spin at 16 k×g for 20 min; the supernatant was placed through a second spin for 30 min at 50 k×g; finally the supernatant from the second spin was placed through a third spin for 60 min at 100 k×g. The final RCP/SWNT supernatant (˜2 μL) was spotted on a SpectRim substrate (Tienta Sciences, Inc.; Indianapolis, Ind.) and allowed to dry in a dessicator overnight prior to Raman analysis. Drying RCP/SWNT dispersions prepared by high-speed centrifugation did not induce the formation of RCP/SWNT bundles on substrates, as demonstrated by AFM of the dried material ( FIG. 7 ), similar to previous results with other peptide/SWNT dispersions studied (18). Thus, drying does not make bundles that could influence the Raman spectra. For samples containing SDS, no TCEP was added.
[0032] Dispersive Raman spectra were recorded on a Jobin Yvon Horiba high resolution LabRam Raman microscope system. The laser excitation was provided by a Spectra-Physics model 127 helium-neon laser operating at 633 nm with 20 mW output power (laser in resonance with both metallic and semiconducting CNTs), using a 10× objective lens and a 25 μm slit. The laser power at the sample was ˜8 mW and was focused to ˜1 μm. Wavenumber calibration was carried out using the 520.5 cm −1 line of a silicon wafer. The spectra of peptide/SWNT and SDS/SWNT dispersions were recorded by scanning the 50 to 2000 cm −1 region for a total acquisition time of 8 min.
[0033] Atomic Force Microscopy (AFM). Samples were prepared as described in the Raman section. The 100 k×g supernatants were diluted 10-fold with degassed DI water, and 10 μL volumes were dropped onto freshly cleaved muscovite mica (Asheville-Schoonmaker Mica Co.). Samples were placed in a dessicator to dry for 24 h prior to AFM imaging. AFM images (2.0×2.0 μm) were acquired in air under ambient conditions using a Digital Instruments, Inc. Nanoscope III Multimode Scanning Probe Microscope operated in the TappingMode™ with 5.0 N m −1 force constant cantilevers and a reduced Z-limit (100 V)(18). The AFM scanner was calibrated using a NanoDevices, Inc., standard of lines with 2 μm pitch and 20 nm height, dimensions similar to those of SWNTs. The height calibration was verified to be 0.3% accurate using hydrofluoric acid etched pits in muscovite mica where 2 nm steps are observed along the long axis and 1 nm steps are observed along the short axis (25).
[0034] RCP Design. The appropriate peptide lengths for wrapping SWNTs of different diameters were determined using computer models of RCPs encircling SWNTs. Optimized RCP models suggest that peptides with 11 amino acids (40 backbone atoms) and 15 amino acids (52 backbone atoms) should be sufficient to encircle SWNTs with diameters of 1.15 and 1.49 nm, respectively. An additional 7 atoms per peptide come from modifications to the N- and C-termini, yielding the peptides RC5 and RC7 ( FIG. 1B ). The resulting RCPs contain two free thiols, which enable the formation of closed rings upon intramolecular reactions to create disulfide bonds. Both RC5 and RC7 reversibly convert between reduced (linear) and oxidized (cyclized) states, with monomers being the predominant form in a 100 μM peptide solution (21).
[0035] SWNT Solubilization by RCPs. The solubilization of HiPco SWNTs by RC5 and RC7 was studied by sonicating SWNTs in the presence of aqueous RCP solutions and monitoring the SWNT absorbance at 375 nm to determine the amount of dispersed SWNTs. With a reduced (linear) RCP solution, a black dispersion formed, characteristic of SWNTs in solution, for which A 375 intensified with increased sonication time ( FIG. 2 ). This increase in SWNT concentration with increased sonication time also correlated with a decrease in reduced RCP as measured by the Ellman test ( FIG. 2 ); taken together, these results suggest that sonication leads to peptide oxidation (cyclization) with concurrent CNT solubilization.
[0036] The amount of SWNTs solubilized also depends on whether the RCP is in the linear (reduced) or cyclized (oxidized) form. When the RCP was initially open, high levels of SWNT solubilization occurred after sonication ( FIGS. 2 and 3 ); however, solubilization was significantly less efficient with RCPs that were initially in the cyclized state ( FIG. 3 ). The small amount of CNTs observed in vials 1 and 3 of FIG. 3 may be due to weak interactions between Lys side chains on each RCP exterior and the CNTs; RC5 (vial 1) has fewer Lys residues than RC7 (vial 3), so under the same conditions the longer peptide should yield a slightly higher nanotube solubilization. When control peptides were used that have the same AA sequence as the RCPs but lack terminal thiol groups, less SWNT solubilization occurred
[0037] FIG. 2 is a graph that shows the Percent reduced RC7 in dispersion as a function of sonication time (Left axis, red solid line) (measured by Ellman test) and, on the Right axis, blue dotted line, A 375 for RC7/SWNT dispersion as a function of sonication time (data not shown). In addition, when β-mercaptoethanol was added to an RCP/SWNT dispersion to disrupt RCP disulfides, a majority of the SWNTs precipitated out of solution (data not shown). Furthermore, dilution of RCP/SWNT dispersions with water resulted in minimal SWNT precipitation, suggesting that the RCPs were very tightly bound to SWNTs as predicted if the RCPs were covalently closed around the CNTs. Taken together, these data strongly suggest that RCPs solubilize and stabilize SWNTs in aqueous solution by wrapping around the circumference of the CNTs, forming rings closed by disulfide bonds.
[0038] FIG. 3 shows the oxidation state of: (Tube 1) RC5 initially oxidized (cyclized), sonicated in presence of SWNTs; (Tube 2) RC5 initially reduced (linear), oxidized in presence of SWNTs; (Tube 3) RC7 initially oxidized (cyclized), sonicated in presence of SWNTs; (Tube 4) RC7 initially reduced (linear), oxidized in presence of SWNTs. For all samples, a 4 min sonication time was used, followed by 16 k×g centrifugation for 10 min.
[0039] Optical Spectroscopy. The optical absorption spectra of RC5/SWNT and RC7/SWNT dispersions show multiple well-defined peaks from the visible to NIR regions ( FIG. 4 ). The peaks represent optical transitions between singularities for a specific type of tube (n, m) and are evidence that RCPs efficiently debundle HiPco SWNTs. Moreover, for a given peptide concentration, dispersions made with RC7 reproducibly absorb more strongly than those made with RC5. Each RCP, when cyclized, should solubilize all individual SWNTs with diameters smaller than the cyclized peptide's inner pore. Since RC7 is longer, its inner pore when cyclized should be larger and so should solubilize a larger population of SWNTs than cyclized RC5, giving rise to the higher absorbance observed in FIG. 4 .
[0040] Raman Spectroscopy. Diameter selection is further substantiated by Raman spectroscopy of samples centrifuged at different speeds. Centrifugation should remove CNT bundles that are not diameter selected by RCP wrapping. Therefore, following centrifugation, the diameter distribution of individual SWNTs that are wrapped and maintained in solution by the RCPs can be analyzed. At a constant excitation wavelength (either 633 or 488 nm; 488 nm excitation data not shown), the radial breathing modes (RBMs) of the Raman spectra show intensity changes as a function of centrifugation speed (see FIGS. 5A and 5B ). The same bands were observed in dispersions centrifuged at 16 k×g and 100 k×g; however, the relative intensities depended on the peptide. For the 633 nm excitation, for example, the bands at 252, 282 and 296 cm −1 (corresponding to SWNTs with approximate diameters between 0.79 and 0.94 nm (26, 27)) are significantly enhanced as the RC5 sample is spun faster, whereas the band at 218 cm −1 (˜1.1 nm diameter SWNTs) is decreased in intensity ( FIG. 5A ). A similar pattern is observed for the RC7/SWNT dispersion ( FIG. 5B ); however, whereas the 252 and 282 cm −1 bands invert their relative intensities for the RC5 sample at faster centrifugation speeds, the relative intensities in the RC7/SWNT dispersion remain similar. Similar patterns are also observed for the RBMs at a 488 nm excitation (data not shown).
[0041] FIGS. 5A to 5 D are graphs of ( 5 A and 5 B) Raman RBM regions of RC5/SWNT ( 5 A) and RC7/SWNT ( 5 B) dispersions (red, 16 k×g, 20 min; blue, 100 k×g, 1 hr; 633 nm excitation).
[0042] FIGS. 5C and 5D are comparisons of RBM regions of RC5/SWNT (red) and RC7/SWNT (blue) dispersions excited at 633 nm ( 5 C) and 488 nm ( 5 D). All spectra were normalized to the band at ˜200 cm −1 .
[0043] The Raman results at different centrifugation speeds suggest a selective enhancement of smaller diameter SWNTs as the samples are spun faster, with a more significant enhancement occurring for RC5, evidence that smaller diameter SWNTs are enriched in the RC5 samples. If this effect were due simply to decreasing the concentration of the more dense CNTs in solution at higher speeds (and not to a diameter-selective solubilization), then t a decrease in the RBM features owing to the removal of the smaller diameter (more dense) CNTs would be expected, however, the opposite trend was obaserved. The densities associated with RC5/(11,3)-SWNT and RC7/(14,5)-SWNT systems were calculated based on our molecular models, including in each calculation all backbone atoms for a single RCP molecule and all carbon atoms in a 10 Å-long slice of a single SWNT; results of the calculations indicate that the smaller diameter RC5/(11,3)-SWNT system is ˜6% more dense. For a control system in which diameter selection should not be observed, an SDS-solubilized HiPco CNTs was prepared and subjected to the same centrifugation procedure used for the RCP/SWNT preparations. As shown in FIG. 6 , the RBM signals at higher wavenumbers are repressed in the 100 k×g sample, indicating that larger diameter CNTs are indeed retained.
[0044] FIG. 6 is a graph of the Raman RBM regions of SDS/SWNT dispersion (red, 16 k×g, 20 min; blue, 100 k×g, 1 hr; 633 nm excitation). Spectra were normalized to the band at ˜200 cm −1 . A similar enhancement is observed at a fixed centrifugation speed (100 k×g) when comparing the RBMs for the RC5/SWNT and RC7/SWNT samples at both 633 and 488 nm excitations. The enhancement is seen for the 282 cm −1 band in the RC5 sample at 633 nm ( FIG. 5C ) and for the 265 cm −1 band in the RC5 sample at 488 nm ( FIG. 5D ). This demonstrates that the observed changes are not artifacts of a given excitation wavelength.
[0045] AFM Height Analysis. Support for diameter selection is also provided by AFM measurements conducted on the RCP/SWNT dispersions. With careful calibration of the scanner, height measurements can be used to accurately determine CNT diameters (18). RC5 and RC7 are expected to encircle SWNTs with diameters less than or equal to 1.15 and 1.49, respectively. If the peptide backbones of the RCPs are added to the SWNT diameters, the diameters are 1.86 nm (RC5/SWNTs) and 2.22 nm (RC7/SWNTs), respectively ( FIG. 7A ). Peptide side chains were not included in the calculated diameters because the AFM samples are dried; the side chains are expected to collapse onto the surface of the RCP/SWNT structure and not contribute significantly to the measured diameters.
[0046] AFM images of the RC5/SWNT and RC7/SWNT dispersions reveal well-dispersed SWNTs ( FIG. 7B , C). The diameters of the CNTs do not appear completely uniform along their lengths. Rather, the CNTs exhibit smooth regions interrupted by brighter “beaded” areas. These features are possibly associated with bare CNTs (smooth regions) and peptide-wrapped segments (beaded areas). Diameter measurements were obtained at multiple points along each CNT in both the smooth and beaded areas ( FIG. 7D ). For the smooth regions, the diameter distribution for the RC7 sample is shifted significantly to higher diameters compared to the RC5 sample ( FIG. 7E ). The diameters range from 0.79 to 1.27 nm for the RC5/SWNT sample vs. 0.91 to 1.45 nm for the RC7/SWNT sample (Table 1). A test for unequal variances performed at the 95% confidence level revealed that the average diameters taken along smooth and beaded regions of a CNT can be distinguished between RC5/SWNT and RC7/SWNT samples (Table 1). Importantly, these diameter distributions are both significantly smaller than that observed for nano-1-wrapped HiPco SWNTs (18), suggesting that the RCPs solubilize CNTs with smaller diameters.
[0047] In the beaded regions, the measured diameters are significantly larger than those in the smooth regions. The measured diameters range from 1.41 to 1.79 nm for the RC5/SWNT sample and from 1.24 to 2.15 nm for the RC7/SWNT sample. These diameters are on average 0.47 and 0.61 nm larger than the smooth regions for RC5 and RC7, respectively, which is close to the expected value of 0.7 nm additional thickness for a single peptide backbone layer surrounding the CNT circumference ( FIG. 7A ). These AFM measurements strongly support our model for RCP wrapping of SWNTs, displaying diameter distributions consistent with diameter-selective solubilization.
[0048] FIG. 7A shows the expected dimensions for RC5/SWNT and RC7/SWNT structures. FIGS. 7B and 7C are 1.0×1.0 μm AFM images of diluted 100 k×g RC5/SWNT ( 7 B) and RC7/SWNT ( 7 C) dispersions. FIG. 7D (left) is an AFM height profile taken along the length of a single nanotube ( 7 D, right AFM image, 0.5×0.5 μm), showing the differences between the smooth and beaded areas (beaded areas indicated by arrows). FIG. 7E shows the measured diameter distributions (smooth regions) for diluted 100 k×g RC5/SWNT and RC7/SWNT dispersions (n=100; four 2.0×2.0 μm images, two samples for each peptide).
TABLE 1 Statistical analysis of AFM height measurements. RC5/SWNT RC7/SWNT By Nanotube Smooth Bead Smooth Bead Mean (nm) a 0.98 1.45 1.12 1.73 Std. Dev. (nm) 0.13 0.22 0.15 0.30 Std. Dev. of Mean (nm) 0.03 0.06 0.03 0.09 Minimum (nm) 0.79 1.41 0.91 1.24 Maximum (nm) 1.27 1.79 1.45 2.15 n b 17 15 20 11 a For each individual nanotube, the mean values for the smooth and beaded regions were calculated. The entries in the table represent the average of the means determined for each nanotube. The height data were also analyzed by separately averaging all smooth and all beaded points for each RCP/SWNT sample (i.e. not calculating a mean for each nanotube), and the results were essentially identical to those reported in this table (not shown). b Number of nanotubes per AFM image. The n is different for smooth and beaded regions in a given RCP/SWNT sample because some nanotubes (2 for the RC5/SWNT sample; 9 for the RC7/SWNT sample) did not have beaded regions present (i.e. were completely smooth).
[0049] Limited Diameter Selection. Although RC5 appears to select, on average, smaller diameter SWNTs than RC7, the selection is not absolute (i.e., RBM bands corresponding to SWNTs larger than 1.0 nm diameter are present in both RCP samples, and a sharp diameter cutoff is not observed in the AFM data). One possible explanation is that the RCPs can polymerize, a known occurrence at high local RCP concentrations (data not shown). Although the peptide concentrations used in this study do not promote significant polymerization in solution, high local concentrations could form if multiple RCPs interacting with the same CNT were in close proximity on the tube surface. Oxidation could then lead to polymerization. Polymers composed of two or more RCP molecules would then be able to wrap SWNTs of various diameters, including those that were too large to be solubilized by cyclized RCP monomers ( FIG. 8 ), thus providing a population of SWNTs in the RC5/SWNT dispersion with diameters larger than those allowed by cyclized RCPs.
[0050] FIG. 8 shows two models showing possible polymerization of RCPs around SWNTs (C, green; H, white; N, blue; O, red; S, yellow; SWNT, pink). A novel to coat SWNTs with reversible cyclic peptides that covalently close around CNTs was developed through oxidation of thiols incorporated into the peptide backbone. By controlling the length of the RCPs a limited diameter-selective solubilization of HiPco SWNTs was developed for SWNT purification. In addition, RCPs covalently closed around SWNTs do not dissociate from the SWNTs unless the disulfide bond is reduced. RCPs thus provide a platform to which other functional groups could be attached without disturbing the covalent structure of SWNTs.
[0051] It will be understood that particular embodiments described herein are shown by way of illustration and not as limitations of the invention. The principal features of this invention can be employed in various embodiments without departing from the scope of the invention. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific procedures described herein. Such equivalents are considered to be within the scope of this invention and are covered by the claims.
[0052] All publications and patent applications mentioned in the specification are indicative of the level of skill of those skilled in the art to which this invention pertains. All publications and patent applications are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.
[0053] All of the compositions and/or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and/or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. More specifically, it will be apparent that certain agents which are both chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.
REFERENCES
[0000]
(1) Baughman, R. H.; Zakhidov, A. A.; de Heer, W. A. Science 2002, 297, 787-792.
(2) Moore, V. C.; Strano, M. S.; Haroz, E. H.; Hauge, R. H.; Smalley, R. E.; Schmidt, J.; Talmon, Y. Nano Lett. 2003, 3, 1379-1382.
(3) Dalton, A. B.; Blau, W. J.; Chambers, G.; Coleman, J. N.; Henderson, K.; Lefrant, S.; McCarthy, B.; Stephan, C.; Byrne, H. J. Synth. Met. 2001, 121, 1217-1218.
(4) O'Connell, M. J.; Boul, P.; Ericson, L. M.; Huffman, C.; Wang, Y. H.; Haroz, E.; Kuper, C.; Tour, J.; Ausman, K. D.; Smalley, R. E. Chem. Phys. Lett. 2001, 342, 265-271.
(5) Dieckmann, G. R.; Dalton, A. B.; Johnson, P. A.; Razal, J.; Chen, J.; Giordano, G. M.; Munoz, E.; Musselman, I. H.; Baughman, R. H.; Draper, R. K. J. Am. Chem. Soc. 2003, 125, 1770-1777.
(6) Wang, S.; Humphreys, E. S.; Chung, S.-Y.; Delduco, D. F.; Lustig, S. R.; Wang, H.; Parker, K. N.; Rizzo, N. W.; Subramoney, S.; Chiang, Y.-M.; Jagota, A. Nat. Mat. 2003, 2, 196-200.
(7) Zheng, M.; Jagota, A.; Semke, E. D.; Diner, B. A.; Mclean, R. S.; Lustig, S. R.; Richardson, R. E.; Tassi, N. G. Nat. Mat. 2003, 2, 338-342.
(8) Zheng, M.; Jagota, A.; Strano, M. S.; Santos, A. P.; Barone, P.; Chou, S. G.; Diner, B. A.; Dresselhaus, M. S.; Mclean, R. S.; Onoa, G. B.; Samsonidze, G. G.; Semke, E. D.; Usrey, M. L.; Walls, D. J. Science 2003, 302, 1545-1548.
(9) Duesberg, G. S.; Muster, J.; Krstic, V.; Burghard, M.; Roth, S. Appl. Phys. A: Mater. Sci. Process. 1998, 67, 117-119.
(10) Duesberg, G. S.; Blau, W.; Byrne, H. J.; Muster, J.; Burghard, M.; Roth, S. Syn. Met. 1999, 103, 2484-2485.
(11) Doom, S. K.; Fields, R. E., III; Hu, H.; Hamon, M. A.; Haddon, R. C.; Selegue, J. P.; Majidi, V. J. Am. Chem. Soc. 2002, 124, 3169-3174.
(12) Farkas, E.; Anderson, M. E.; Chen, Z. H.; Rinzler, A. G. Chem. Phys. Lett. 2002, 363, 111-116.
(13) Doom, S. K.; Strano, M. S.; O'Connell, M. J.; Haroz, E. H.; Rialon, K. L.; Hauge, R. H.; Smalley, R. E. J. Phys. Chem. B 2003, 107, 6063-6069.
(14) Strano, M. S.; Zheng, M.; Jagota, A.; Onoa, G. B.; Heller, D. A.; Barone, P. W.; Usrey, M. L. Nano Lett. 2004, 4, 543-550.
(15) Heller, D. A.; Mayrhofer, R. M.; Baik, S.; Grinkova, Y. V.; Usrey, M. L.; Strano, M. S. J. Am. Chem. Soc. 2004, 126, 14567-14573.
(16) Boul, P. J.; Liu, J.; Mickelson, E. T.; Huffman, C. B.; Ericson, L. M.; Chiang, I. W.; Smith, K. A.; Colbert, D. T.; Hauge, R. H.; Magrave, J. L.; Smalley, R. E. Chem. Phys. Lett. 1999, 310, 367-372.
(17) Chattopadhyay, D.; Galeska, I.; Papadimitrakopoulos, F. J. Am. Chem. Soc. 2003, 125, 3370-3375.
(18) Zorbas, V.; Ortiz-Acevedo, A.; Dalton, A. B.; Yoshida, M. M.; Dieckmann, G. R.; Draper, R. K.; Baughman, R. H.; Jose-Yacaman, M.; Musselman, I. H. J. Am. Chem. Soc. 2004, 126, 7222-7227.
(19) Ghadiri, M. R.; Granja, J. R.; Milligan, R. A.; McRee, D. E.; Khazanovich, N. Nature 1993, 366, 324-327.
(20) Bong, D. T.; Clark, T. D.; Granja, J. R.; Ghadiri, M. R. Angew. Chem. Int. Ed. 2001, 40, 988-1011.
(21) Ortiz-Acevedo, A.; Dieckmann, G. R. Tet. Lett. 2004, 45, 6795-6798.
(22) Nikolaev, P.; Bronikowski, M.; Bradley, R.; Rohmund, F.; Colbert, D.; Smith, K.; Smalley, R. E. Chem. Phys. Lett. 1999, 313, 91-97.
(23) Okamoto, H.; Nakanishi, T.; Nagai, Y.; Kasahara, M.; Takeda, K. J. Am. Chem. Soc. 2003, 125, 2756-2769.
(24) Ellman, G. L.; Courtney, K. D.; Andres, V., Jr.; Feather-Stone, R. M. Biochem. Pharmacol. 1961, 7, 88-95.
(25) Nagahara, L. A.; Hashimoto, K.; Fujishima, A. J. Vac. Sci. Technol. B. 1994, 12, 1694-1697.
(26) Bachilo, S. M.; Strano, M. S.; Kittrell, C.; Hauge, R. H.; Smalley, R. E.; Weisman, R. B. Science 2002, 298, 2361-2366.
(27) Karachevtsev, V. A.; Glamazda, A. Y.; Dettlaff-Weglikowska, U.; Kumosov, V. S.; Obraztsova, E. D.; Peschanskii, A. V.; Eremenko, V. V.; Roth, S. Carbon 2003, 41, 1567-1574. | The present invention includes compositions and methods for the isolation, separation and chelation of Carbon Nanotubes (CNTs) using a cyclizable peptide. | 2 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a division of U.S. patent application Ser. No. 12/140,940 filed Jun. 17, 2008. U.S. patent application Ser. No. 12/140,940 is a continuation of and claims priority to U.S. patent application Ser. No. 09/881,052, entitled Oligonucleotide Synthesizer, filed Jun. 13, 2001, now U.S. Pat. No. 7,390,459 issued Jun. 24, 2008, which is continuation-in-part of and claims priority to U.S. patent application Ser. No. 09/738,473, entitled Oligonucleotide Synthesizer, filed Dec. 13, 2000, now U.S. Pat. No. 6,663,832 issued Dec. 16, 2003, which is a non-provisional application of and claims priority to U.S. Provisional Patent Application No. 60/170,314, entitled Oligonucleotide Synthesizer, filed Dec. 13, 1999, the entire contents of which applications are incorporated herein by this reference.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH
[0002] This invention was made with government support under 2 R44 GM58981-02A1 awarded by the National Institutes of Health. The government has certain rights in the invention.
BACKGROUND OF THE INVENTION
[0003] 1. Field of the Invention
[0004] The present invention relates to the field of devices and methods for chemical synthesis, analysis, and biological screening. More particularly, the present invention relates to a new and improved apparatus for high-throughput combinatorial synthesis of organic molecules, particularly nucleic acids.
[0005] 2. Description of Related Art
[0006] Solid-phase synthesis of organic molecules is the method of choice for preparation of libraries and compound megaarrays, which are currently being applied for screening in the quest to find new drugs or pharmaceutical lead compounds, i.e., compounds which exhibit a particular biological activity of pharmaceutical interest. These leads can serve as a starting point for the selection and synthesis of a drug compound, which in addition to the particular biological activity of interest has pharmacologic and toxicologic properties suitable for administration to animals, including humans.
[0007] Several designs of instruments for combinatorial synthesis utilizing solid-phase synthesis are known. An exemplar of the prior art is U.S. Pat. Nos. 5,202,418 and 5,338,831, to Lebl et al., which each describe a method of performing multiple synthesis of peptides on a solid carrier. U.S. Pat. No. 5,342,585 to Lebl et al. describes an apparatus for multiple syntheses of peptides on solid support. U.S. Pat. No. 6,045,755 to Lebl, et al. describes an apparatus and a method fiSr combinatorial chemistry synthesis. U.S. Pat. No. 6,121,054 to Lebl, corresponding to PCT International Publication No. W000/25470, shows a method for separation of liquid and solid-phases for solid-phase organic synthesis. The entire contents of the above patents are incorporated herein by this reference.
[0008] Liquid removal by centrifugation was described and is the subject of several publications. See Christian Birr, Aspects of the Merrified Peptide Synthesis (Springer-Verlag, New York 1978; German Patent Application P 20 17351.7, G. 70 13256.8, 1970. These references describe the use of centrifugation for liquid removal from slurry of solid-phase particles in a concentric vessel equipped with a filtration material in its perimeter and spun around its axis.
SUMMARY OF THE INVENTION
[0009] In summary, one aspect of the present invention is directed to an apparatus for performing combinatorial-chemistry synthetic reactions including a reaction vessel for containing a combinatorial-chemistry synthetic reaction, a liquid dispenser for dispensing the liquid, and a liquid aspirator and an adjustment mechanism. The reaction vessel includes an ingress aperture allowing a liquid to enter into an interior of the vessel and an egress aperture for aspirating the liquid from the vessel. The liquid dispenser dispenses liquid through the ingress aperture. The liquid aspirator aspirates liquid through the egress aperture and includes a rotor for carrying the vessel and orbiting the vessel about an axis of rotation. The rotor is oriented generally in a horizontal plane and includes an adjustment mechanism for adjusting the angle of the vessel relative to the horizontal plane in response to the centrifugal force generated by orbiting the vessel about the axis of rotation. The dispenser
[0010] Another aspect of the present invention is directed to an apparatus for dispensing liquids into a reaction vessel including a rotor, a liquid dispenser, and a controller. The rotor is mounted for rotation about a central axis and carries an array of reaction vessels along a circular path. The liquid dispenser includes a plurality of dispensing nozzles and is positioned above the rotor. The liquid dispenser is arranged for dispensing a liquid from each dispensing nozzle into a respective reaction vessel while the array of reaction vessels moves along the circular path past the liquid dispenser. The controller synchronizes the liquid dispenser and the array of reaction vessels such that the liquid dispenser dispenses liquid into the array of reaction vessels while the rotor is moving.
[0011] Another aspect of the present invention is directed to an apparatus for dispensing liquids including a plate and a plurality of dispensing nozzles. The plate includes a first circular array of reaction vessels and a second circular array of reaction vessels. The first and second circular arrays are concentrically arranged about a central axis. The plurality of dispensing nozzles is arranged in a circular pattern above the plate. Each dispensing nozzle is mounted for radial movement about the central axis.
[0012] Yet another aspect of the present invention is directed to an apparatus for chemical synthesis utilizing a plate having a plurality of reaction wells therein. The apparatus includes a plate holder, a first reagent dispensing nozzle, an inverting mechanism, and a second solution dispensing nozzle. The plate holder supports the plate in a plurality of positions. The first reagent dispensing nozzle is positioned to dispense a reagent into the plurality of reaction wells for chemical reaction with chemical moieties within the reaction wells when the plate holder supports the plate in an upright position. The inverting mechanism inverts the plate holder and moves the plate between the upright position and an inverted position. The second solution dispensing nozzle is positioned to dispense a solution into the reaction wells when the plate is inverted so that at least a part of the solution can drain by gravity from the reaction wells.
[0013] In general, it is an object of the present invention is to provide an apparatus for reagent delivery during solid-phase synthetic reactions while the dispensing head and rotor are moving and aligned.
[0014] Another object of the present invention is to provide an apparatus having an improved fluid delivery system and an improved centrifugal rotor assembly.
[0015] Another object of the present invention is to provide an apparatus for custom chemical synthesis that is easy to operate, has low initial cost, runs on convenient and easy-to-install consumables, and provides high-throughput combinatorial synthesis of organic molecules.
[0016] Yet another object of the present invention is to provide an apparatus for providing continuous liquid addition with respect to motion of the rotor and the fluid delivery system.
[0017] The accompanying drawings, which are incorporated in and form a part of this specification, illustrate embodiments of the invention and, together with the description, serve to explain the principles of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] FIG. 1 is a perspective view of an apparatus for high-throughput combinatorial syntheses of organic molecules in accordance with the present invention.
[0019] FIG. 2 is an enlarged perspective view of a portion of the apparatus shown in FIG. 1 showing a rotor assembly supporting a microtiter plate including a plurality of wells in accordance with the present invention.
[0020] FIG. 3 is an enlarged schematic view of the microtiter plate of FIG. 2 passing beneath nozzles of a liquid delivery system in accordance with the present invention.
[0021] FIG. 4 is a top plan view of a portion of the apparatus of FIG. 1 having a modified liquid delivery system in accordance with the present invention.
[0022] FIGS. 5( a ) and 5 ( b ) are a graphs illustrating dispensing head motion along respective X- and Y-axis, of the apparatus of FIG. 1 in accordance with the present invention.
[0023] FIGS. 6( a ) and 6 ( b ) are graphs illustrating well motion along respective X- and Y-axis, of the apparatus of FIG. 1 in accordance with the present invention.
[0024] FIG. 7( a ) is an enlarged, detailed, and exploded view of a nozzle and fluid connector of the apparatus shown in FIG. 1 in accordance with the present invention.
[0025] FIG. 7( b ) is an enlarged, fragmented, and exploded view of a portion of the nozzle and fluid connector of FIG. 7( a ).
[0026] FIG. 8( a ) is an enlarged, partial perspective view of rotor assembly of FIG. 2 .
[0027] FIG. 8( b ) is a sectional view of a portion of the rotor assembly of FIG. 2 taken along line 8 ( b )- 8 ( b ).
[0028] FIG. 9 is a partial top plan view of the rotor assembly of FIG. 2 having a modified biasing mechanism in accordance with the present invention.
[0029] FIG. 10( a ) is a perspective view of a modified microtiter plate including reaction wells similar to that shown in FIG. 2 . FIGS. 10( b ), and 10 ( c ) are perspective views of a rotor and an individual reaction well, respectively, similar to the reaction wells of FIG. 10( a ).
[0030] FIGS. 11( a ), 11 ( b ), 11 ( c ), and 11 ( d ) are schematic views of a portion of a modified apparatus including filtering means located within modified wells in accordance with the present invention similar to those of FIG. 2 .
[0031] FIGS. 12( a ) and 12 ( b ) are schematic views of wells in accordance with the present invention similar to those of FIG. 11 .
[0032] FIG. 13 is a schematic views of a well in accordance with the present invention similar to those of FIG. 11 .
[0033] FIG. 14 is a perspective view of a modified apparatus in accordance with the present invention similar to the apparatus shown in FIG. 1 .
[0034] FIG. 15 , is a perspective view of a modified rotor in accordance with the present invention similar to the rotor of FIG. 10( b ).
[0035] FIGS. 16( a ) and 16 ( b ) are top plan views of a spiral translation mechanism of the apparatus of FIG. 14 in accordance with the present invention.
[0036] FIGS. 17( a ) and 17 ( b ) are schematic side and top plan views, respectively, of modified apparatus for high-throughput combinatorial syntheses of organic molecules in accordance with the present invention similar to the apparatus of FIG. 1 .
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0037] Reference will now be made in detail to the preferred embodiments of the invention, examples of which are illustrated in the accompanying drawings. While the invention will be described in conjunction with the preferred embodiments, it will be understood that they are not intended to limit the invention to those embodiments. On the contrary, the invention is intended to cover alternatives, modifications and equivalents, which may be included within the spirit and scope of the invention as defined by the appended claims.
[0038] The present invention is directed to solid-phase, combinatorial chemistry synthesis of organic molecules. In particular, the apparatus of the present invention is particularly suited for solid-phase synthesis of oligomers using a centrifuge. Preferably, the apparatus of the present invention utilizes solid-phase particles such as microbeads for organic synthesis of oligomers. The apparatus of the present invention utilizes a centrifuge with a rotor for the step-wise addition and removal of solid and liquid phase solutions and the separation and removal of the solid-phase particles for synthetic reactions, as is described in U.S. Pat. No. 6,121,054 to Lebl entitled Method for Separation of Liquid and Solid Phases for Solid Phase Organic Synthesis, the entire contents of which is incorporated by this reference.
[0039] The oligonucleotides synthesized using the present invention are used in one of two ways. In one embodiment, and the beads comprising the oligonucleotides are directly dispersed on a bead array such as is generally described in PCT/US98/21193, PCT/US99/04473, PCT/US98/05025, PCT/US99/14387, and U.S. patent application Ser. Nos. 09/287,573, 09/256,943, 09/316,154, 09/425,633, 09/425,633, 60/161,148 for and 60/160,917, the entire contents of which are incorporated herein by this reference. Alternatively, the oligonucleotides may be cleaved from the synthesis support and added to different sets of beads for use in the bead arrays.
[0040] By way of introduction, in a preferred embodiment of the present invention is generally directed to the synthesis of nucleic acids. The terms “nucleic acid” or “oligonucleotide,” and other grammatical equivalents herein, referred to at least two nucleotides covalently linked together. A nucleic acid of the present invention will generally contain phosphodiester bonds, although in some cases, as outlined below, nucleic acid analogs are included that may have alternate backbones, comprising, for example, phosphoramide (Beaucage et al., Tetrahedron 49(10):1925 (1993) and references therein; Letsinger, J. Org. Chem. 35:3800 (1970); Sprinzl et al., Eur. J. Biochem. 81:579 (1977); Letsinger et al., Nucl. Acids Res. 14:3487 (1986); Sawai et al, Chem. Lett. 805 (1984), Letsinger et al., J. Am. Chem. Soc. 110:4470 (1988); and Pauwels et al., Chemica Scripta 26:141 91986)), phosphorothioate (Mag et al., Nucleic Acids Res. 19:1437 (1991); and U.S. Pat. No. 5,644,048), phosphorodithioate (Briu et al., J. Am. Chem. Soc. 111:2321 (1989)), 0-methylphosphoroamidite linkages (see Eckstein, Oligonucleotides and Analogues: A Practical Approach, Oxford University Press), and peptide nucleic acid backbones and linkages (see Egholm, J. Am. Chem. Soc. 114:1895 (1992); Meier et al., Chem. Int. Ed. Engl. 31:1008 (1992); Nielsen, Nature, 365:566 (1993); Carlsson et al., Nature 380:207 (1996), all of which are incorporated by reference). Other analog nucleic acids include those with positive backbones (Denpcy et al., Proc. Natl. Acad. Sci. USA 92:6097 (1995); non-ionic backbones (U.S. Pat. Nos. 5,386,023, 5,637,684, 5,602,240, 5,216,141 and 4,469,863; Kiedrowshi et al., Angew. Chem. Intl. Ed. English 30:423 (1991); Letsinger et al., J. Am. Chem. Soc. 110:4470 (1988); Letsinger et al., Nucleoside & Nucleotide 13:1597 (1994); Chapters 2 and 3, ASC Symposium Series 580, “Carbohydrate Modifications in Antisense Research”, Ed. Y. S. Sanghui and P. Dan Cook; Mesmaeker et al., Bioorganic & Medicinal Chem. Lett. 4:395 (1994); Jeffs et al., J. Biomolecular NMR 34:17 (1994); Tetrahedron Lett. 37:743 (1996)) and non-ribose backbones, including those described in U.S. Pat. Nos. 5,235,033 and 5,034,506, and Chapters 6 and 7, ASC Symposium Series 580, “Carbohydrate Modifications in Antisense Research”, Ed. Y. S. Sanghui and P. Dan Cook. Nucleic acids containing one or more carbocyclic sugars are also included within the definition of nucleic acids (see Jenkins et al., Chem. Soc. Rev. (1995) pp169-1′76). Several nucleic acid analogs are described in Rawls, C & E News Jun. 2, 1997 page 35. In addition nucleic acids include, “locked nucleic acids” such as those described in Koshkin et al., J. Am. chem. Soc. 120: 13252-3 (1998). All of these references are hereby expressly incorporated by reference.
[0041] The nucleic acids (sometimes referred to herein as oligonucleotides) can be synthesized using a variety of possible synthetic reactions. In a preferred embodiment, phosphoramidite chemistry is used, with enzymatic techniques and techniques based on photodeprotection useful as well. In addition, any number of nucleic acid analogs and labeled nucleic acids can be made and used. See for example Oligonucleotides and Analogs: A Practical Approach, Ed. F. Eckstein, IRL Press, 1991, hereby incorporated by reference in its entirety.
[0042] One should appreciate however that the present invention is similarly applicable to other chemical protocols having similar functional steps. For example, components of the present invention can be applied to appropriate liquid-phase, combinatorial chemistry synthesis protocols, to other solid- or liquid-phase chemical protocols, or to any combination thereof.
[0043] “Protein” as used herein includes proteins, polypeptides, and peptides. The protein may be made up of naturally occurring amino acids and peptide bonds, or synthetic peptidomimetic structures. The side chains may be in either the (R) or the (S) configuration. In a preferred embodiment, the amino acids are in the (S) or L-configuration. If non-naturally occurring side chains are used, non-amino acid substituents may be used, for example to prevent or retarded in vivo degradations. Proteins can be synthesized using the methods and apparatus of the present invention using standard techniques.
[0044] One aspect of the present invention is directed to the use of plates, such as microtiter plates, which support and contain the solid-phase for solid-phase synthetic reactions. In particular, the microtiter plates house beads that are used as the solid-phase. By “particle” or “microparticle” or “nanoparticle” or “bead” or “microbead” or “microsphere” herein is meant microparticulate matter. As will be appreciated by those in the art, the particles can comprise a wide variety of materials depending on their use, including, but not limited to, cross-linked starch, dextrans, cellulose, proteins, organic polymers including styrene polymers including polystyrene and methylstyrene as well as other styrene co-polymers, plastics, glass, ceramics, acrylic polymers, magnetically responsive materials, colloids, thoriasol, carbon graphite, titanium dioxide, nylon, latex, and TEFLON® may all be used. “Microsphere Detection Guide” from Bangs Laboratories, Fishers, IN, is a helpful guide.
[0045] By way of introduction, combinatorial chemistry synthesis protocols prescribe the sequential addition of building blocks to intermediate, partially synthesized, compounds in order to synthesize a final compound. These protocols are, generally, divided into liquid-phase protocols and solid-phase protocols. In liquid-phase protocols, final compounds are synthesized in solution. Partially synthesized, intermediate compounds are separated from spent reagents between building block addition steps by known means, such as precipitation, fractionation, and so forth. In solid-phase synthesis, final compounds are synthesized attached to solid-phase supports that permit the use of simple mechanical means to separate partially-synthesized intermediate compounds between synthetic steps. Typical solid-phase supports include microbeads having diameters from approximately 30 microns to 300 microns to which intermediate compounds covalently attach.
[0046] Solid-phase combinatorial synthesis typically proceeds according to the following steps. In a first step, reaction vessels are charged with a solid-phase support, typically a slurry of microbeads suspended in a solvent. These microbeads are then preconditioned by incubating them in an appropriate solvent, and the first of the plurality of building blocks or a linker moiety is covalently linked to the microbeads. Subsequently, a plurality of building block addition steps are performed, all of which involve repetitive execution of the following or similar sub-steps, and in a sequence chosen to synthesize a desired compound. First, a sufficient quantity of a solution, which contains the building block moiety selected for addition, is dispensed into the reaction vessels so that the building block moiety is present in a molar excess to the intermediate compound present in the reaction vessel. A sub-step reaction is triggered and promoted by activating reagents and other reagents and solvents, which are also added to the reaction vessel. The reaction vessel is then incubated at a controlled temperature for a time, typically between 5 minutes and 24 hours, sufficient for the building block addition reaction to go to substantial completion. Optionally, during this incubation, the reaction vessels can be intermittently agitated or stirred. Finally, in a last sub-step of building block addition, the reaction vessel containing the solid-phase support with attached intermediate compound is prepared for addition of the next building block by removing the spent reaction fluid and thoroughly washing and reconditioning the solid-phase support. Washing typically involves three to seven cycles of adding and removing a wash solvent. Optionally, during the addition steps, multiple building blocks can be added to one reaction vessel in order to synthesize multiple compounds attached to one solid-phase support, or alternatively, the contents of separate reaction vessels can be combined and partitioned in order that multiple compounds can be synthesized in one reaction vessel with each microbead having only one attached final compound (this is sometimes referred to as a “split and mix” synthesis). After the desired number of building block addition steps, the final compound is present in the reaction vessel and attached to the solid-phase support. The final compounds can be utilized either directly attached to their synthetic solid-phase supports, or alternatively, can be cleaved from their supports. In the latter case, the linker moiety attaching the compound to the solid-phase support is cleaved in a variety of ways, and the final compound, or library of compounds is extracted from the reaction vessel into a liquid phase.
[0047] An exemplary solid-phase combinatorial protocol is that for the synthesis of peptides attached to MBHA resin, which proceeds according to Lam et al., 1991, “A new type of synthetic peptide library for identifying ligand-binding activity,” Nature 354: 82-84. Another exemplary protocol is that for the synthesis of benzodiazepine moieties, which proceeds according to Bunin et al., 1992, “A general and expedient method for the solid-phase synthesis of 1,4-benzodiazepine derivatives,” J. Amer. Chem. Soc., 114: 10997-10998. Exemplary building blocks and reagents are nucleic acids, amino acids, other organic acids, aldehydes, alcohols, and so forth, as well as bifunctional compounds, such as those given in Krchnak et al., 1996, “Synthetic library techniques: Subjective (biased and generic) thoughts and views,” Molecular Diversity, 1: 193-216.
[0048] In view of the large potential numbers of final compounds in combinatorial libraries, it is advantageous that at least some manipulations needed by the synthetic protocols be assisted or performed automatically. In view of the exemplary protocol described, an automated apparatus for combinatorial chemistry synthesis advantageously includes facilities for handling fluids, for manipulating reaction vessels, and for storage of reagents and building blocks. Advantageous facilities for fluid handling include: facilities to accurately dispense solutions and slurries which contain building blocks, solid-phase substrates, reagents, and/or solvents into the reaction vessels; facilities to rapidly and repetitively add wash solvents into the reaction vessels; and facilities to rapidly and accurately remove fluid phases from the reaction vessels leaving behind the solid-phase supports within the reaction vessels with respective attached intermediate compounds. Facilities for manipulating reaction vessels and reaction vessel arrays include: facilities to move reaction vessels and reaction vessel arrays between various stations; facilities for time and temperature controlled incubation of reaction vessels and reaction vessel arrays; and optionally facilities for agitation of reaction vessels during incubation. Each such protocol typically uses many building blocks, perhaps hundreds, a several activating and other reagents, and one or two work solvents. Accordingly, there are storage facilities for: a large number of building blocks solutions, typically 300 or more building blocks solutions or more preferably as many as 600 or more building blocks solutions stored, for example, in arrays; preferably 6 or more preferably 12 or more reagents in larger quantities than for building block solutions; and preferably 3 or more preferably 6 or more of even larger quantities of wash solvents.
[0049] The apparatus of the present invention advantageously permits simultaneous, parallel processing to occur during solid-phase synthesis in order to achieve high synthesis throughput. This is achieved because the design of the apparatus includes a few standardized physical sizes and layouts having a modular nature. Thereby, processing resources can be simultaneously applied to multiple protocols in many reaction vessels which can be sized to achieve high throughput.
[0050] Preferred materials for all elements of the present invention in contact with the synthetic addition reactions, in particular the reaction vessels, must resist the harsh reagents, solvents, and reaction conditions likely to be encountered in the various protocols. In the following detailed description, when solvent resistance is specified and particular materials are not specified, the following exemplary general purpose solvent resistant materials can be used: TEFLON®, plastics including polypropylene, or glass, among others.
[0051] Turning now to the drawings, FIG. 1 illustrates one embodiment of an apparatus 40 according to the present invention that is advantageous for high throughput, multi-protocol combinatorial syntheses. Apparatus 40 is adapted for synthesizing oligomers in each of a plurality of reaction vessels 41 ( FIG. 2 ) which are disposed in arrays, such as the rectangular array of reaction vessels or wells 41 disposed in microtiter plate 42 ( FIG. 2 ). Apparatus 40 generally includes a support enclosure 45 , a rotor assembly 46 ( FIG. 2 ) for supporting one or more microtiter plates 42 , an enclosed support surface 49 , and a liquid delivery system 50 . Support enclosure 45 provides mechanical support for rotor assembly 46 , support surface 49 and liquid delivery system 50 . The support enclosure 45 illustrated in FIG. 1 is approximately 28″×30″×72″ (71 cm×76 cm×183 cm. One should appreciate that the dimensions may vary in order to provide a width, depth and height sufficient support a sufficient number of work stations, tools, and reaction vessel arrays to achieve the desired level of synthetic throughput.
[0052] Rotor assembly 46 is rotatably supported by support enclosure 45 below support surface 49 and rotates about a centrifugal axis 51 which extends substantially orthogonal to support surface 49 . Liquid delivery system 50 includes a reagent delivery station or reagent dispenser 52 and a bulk liquid delivery system or bulk dispenser 53 supported on support surface 49 . Reagent dispenser 52 is a multi-channel dispenser that is capable of simultaneously delivering a plurality of different liquids to corresponding different sets of wells 41 of microtiter plate 42 . Reagent dispenser 52 is also capable of sequentially delivering a plurality of different liquids to wells 41 of microtiter plate 42 . Reagent dispenser 52 is fluidly connected to tubing 55 which, in turn, is connected to storage bottles 56 . Tubing 55 and storage bottles 56 are pressurized in order to deliver liquids to reagent dispenser 52 at a controlled pressure. Alternatively, one or more suitable pumps can be connected to the tubing in order to deliver desired liquids from one or more of the bottles to the reagent dispenser at a controlled pressure. In contrast, bulk dispenser 53 is provided to dispense wash-solvent into the entire array of wells 41 of microtiter plate 42 at one time and may be utilized to implement a plurality of washing steps. Bulk dispenser 53 is similarly connected to tubing 58 which, in turn, is connected to a suitable storage bottle and/or pump located below support surface 49 . Although the illustrated embodiment shows the storage bottles located within support enclosure 45 , one should appreciate that the position of the storage bottles and/or pumps may vary. For example, the bottles and/or pumps may be located external to support enclosure 45 .
[0053] Dispensers 52 and 53 , as well as other components needing more frequent attention by an operator, are preferably disposed above support surface 49 , while facilities needing less frequent attention, such as rotor assembly 46 , a bulk liquid pump and other components requiring less maintenance, are preferably disposed below support surface 49 . The present invention is adaptable to other distribution of processing equipment above and below the support surface. Alternatively, one liquid handling work station can be adapted to both dispense and aspirate work solvents. For example, a bulk liquid dispenser can be configured for operation in a dispensing mode and in a suction or aspiration mode.
[0054] The apparatus shown in FIG. 1 includes a sub-enclosure 54 supporting a drum 142 . Rotor assembly 45 is contained within drum 142 . Drum 142 is adapted for retaining an inert atmosphere within a portion of support enclosure 45 thus maintaining an inert atmosphere in which synthesis takes place. Sub-enclosure 54 is preferably ventilated to contain vapors that escape from drum 142 , The vapors are ventilated out from sub-enclosure 54 via an exhaust duct. Sub-enclosure 54 is generally of a rectangular or cubical shape and preferably includes glass or plastic surfaces which are resistant to the harsh reagents and solvents used during synthesis procedures. Preferably, sub-enclosure 54 includes a slidable access panel 57 which allows an operator ready access to plate 42 and the various components located above support surface 49 . Sub-enclosure 54 contains liquid dispensers 52 and 53 as well as other work stations that must be manipulated within a controlled environment. The sub-enclosure is charged with a heavier than air inert gas, such as argon and/or other inert gases in order to maintain unsealed reaction vessels or open wells 41 in an inert atmosphere.
[0055] Turning now to the liquid delivery system, conventional synthesizers dispense liquid into individual wells of a microtiter plate utilizing a two axis X-, Y positioning system for aligning liquid delivery nozzles with respective wells while a centrifuge is at rest. These systems do find use in some embodiments of the present invention. However, for high-throughput systems, this approach is relatively slow because the rotor assembly or centrifuge must be stopped before liquid delivery can proceed, thus disadvantageously increasing cycle time and reducing throughput.
[0056] Accordingly, in a preferred embodiment, reagent delivery dispenser 52 of the present invention is capable of addressing each well 41 individually while microtiter plate 42 is moving while rotor assembly 46 is spinning about centrifugal axis of rotation 51 . This is possible, in part, because a reagent dispenser head 60 of reagent dispenser 52 is mounted in a reagent dispenser translation frame 62 in order to move with respect to support surface 49 . Translation frame 62 is configured to move reagent dispenser head 60 along three substantially orthogonal axes with respect to the support surface 49 . In particular, X-, Y-, and Z-linear actuators move dispenser head 60 along respective X-, Y-, and Z-axes thereby allowing reagent dispenser 52 to address each well 41 individually by synchronizing the motion of dispenser head 60 with the speed of rotor assembly 46 during centrifugation. Reagent dispenser 52 may be further synchronized to address each well 41 individually by synchronizing the rate of and duration of liquid delivery with the speed of rotor assembly 46 . A reagent dispenser with such a configuration generally requires fewer parts than prior devices because the design of the present invention takes advantage of the motion of the microtiter plates and the centrifuge along a fixed path. The X-, Y-, and Z-linear actuators are synchronized to follow the fixed arcuate path of microtiter plate 42 as it spins with rotor assembly 46 . One should appreciate that a fourth axis, a θ axis, must be included in the event that reagent dispenser 52 is configured to simultaneously address two or more wells 41 in microtiter plate 42 while rotor assembly 46 is in motion.
[0057] In particular, wells 41 are filled as they pass beneath a respective nozzle 65 ′, 65 ″ (shown schematically in FIG. 3 ) of the reagent delivery head which is activated so that liquid delivery is synchronized with microtiter plate 42 movement along the fixed circular path of rotor assembly 46 . Accordingly, reagents can be delivered to individual wells 41 as needed without bringing rotor assembly 46 and microtiter plate 42 to a complete halt. Similarly, the need to move delivery nozzles 65 can be minimized or eliminated. Multiple reagents can be dispensed simply by adding additional nozzles in series. For example, a two channel delivery configuration is shown schematically in FIG. 3 in which one nozzle 65 ′ may fill one set of wells of a microtiter plate with a first reagent R 1 and a second nozzle 65 ″ may fill another set of wells with a second reagent R 2 while microtiter plate 42 remains in motion, as indicated by arrow A.
[0058] Preferably, each column of wells is addressed in parallel. For example, to address an 8×12 well microtiter plate, a set of 8 nozzles, in a manner analogous to an ink-jet print head, can be used to address all 8 wells of a column within a microtiter plate in parallel, that is simultaneously. Delivery would be made to each well in a column as needed. Sets of nozzles positioned in series allow the simultaneous delivery of multiple reagents, as shown in FIG. 3 . Alternatively, single nozzles can be used.
[0059] Such a configuration is conducive to multiple channel delivery of reagents to a microtiter plate having either 96 wells, 384 wells, or more wells arranged in an array on a microtiter plate. In the illustrated embodiment, reagent dispenser head 60 includes an array of forty nozzles arranged on five cartridges 66 ( FIG. 1 ), wherein each cartridge 66 includes eight downwardly directed nozzles (not shown in FIG. 1 ) arranged in a linear fashion. Such a multiple channel delivery allows the simultaneous delivery of five different reagents, for example A, C, G, and T bases and an activator into respective wells 41 in a similar manner that is illustrated in FIG. 3 . Each nozzle is provided with an electric solenoid valve which is capable of liquid delivery in durations of less than one to two milliseconds.
[0060] As noted above, conventional synthesizers dispense liquid into individual wells of a microtiter plate utilizing a two axis XY-positioning system for aligning liquid delivery nozzles with respective wells while a centrifuge is at rest. For example, current methods for dispensing liquids into microtiter plates via automation or robotics generally utilize motion systems acting orthogonally with respect to the orientation of wells within the microtiter plate. The X- and Y-axes of a conventional liquid handling robot correspond to the rows and columns of wells within a microtiter plate. Generally a conventional XY-motion system (or an XYZ-motion system in the case that a vertical axis is required for the aspiration of liquids from a microtiter plate) will manipulate a liquid handling head over a deck composed of an array of microtiter plates. The liquid handling head is typically composed of a linear array of nozzles, connected by tubing to syringe pumps or pressure backed bottles to allow for the accurate and precise transport of liquid either from a source microtiter plate to a destination microtiter plate or the accurate and precise dispensing from bulk sources into microtiter plates.
[0061] Other types of conventional liquid handling devices may not be arranged orthogonally in a convenient manner for liquid handling, depending upon physical geometry dictated by other requirements and designs. One example of this is liquid delivery to a radial arrangement of microtiter plates, as in a microtiter centrifuge. In this arrangement, microtiter plates are located within a circular rotor such that the each long side of a microtiter plate is normal to radial lines at regular intervals, at a distance from the center sufficient to accommodate the number of plates desired within the rotor. The circular rotor is driven by a stepper motor, capable of acceleration, velocity and positional accuracy performance desired for centrifuge operations. Within this arrangement, conventional orthogonal access must be made by halting the circular rotor such that a conventional XY-driven dispenser array may access all the wells within the microtiter plate only while the rotor is halted, that is while the rotor is at rest. For accessing a 96 well microtiter plate, consisting of an 8×12 array of wells, only a conventional X-positioning actuator would be required. For a 384 well microtiter plate, consisting of a 16×24 array of wells, a conventional X-axis positioning device with a discreet two position Y-actuator is sufficient. For densities beyond 384 wells, a Y-position actuator of greater resolution such as a linear ball screw is desirable. This conventional arrangement is satisfactory for accessing the microtiter plates in a static condition, that is when the rotor is at rest. However, the microtiter plate must be immobile while the liquid delivery head is maneuvered over the plate along the X-axis of conventional devices.
[0062] The apparatus of the present invention precisely controls dispensing valves within reagent dispenser 52 to allow dispensation of liquids in to wells 41 without stopping dispenser head 60 . This is accommodated by utilizing a real-time control architecture of the dispensing valves, that is by providing both accurate and precise control of the solenoid valve of each nozzle 65 to valve states, that is initiating a change in state, to within 10-15 milliseconds. This allows the dispensing head to continue moving at a constant rate while the dispensing valves are actuated on demand as they pass over individual wells.
[0063] In another embodiment of the present invention, the apparatus is capable of dispensing liquid into the wells of the microtiter plate without the need to halt either the rotor or the reagent dispenser head 60 . Rotor assembly 46 of the present invention is driven by a compact, powerful stepper motor with high resolution (+/−4000 quadrature counts/revolution). The motor is capable of high acceleration and deceleration rates, velocities up to 4000 RPM, and positioning resolution of +/−0.2 degrees. Active braking of the rotor assembly can also be utilized to further assist in decelerating the rotor assembly. The motor is controlled by a real time, (determinately behaving) controller. In one embodiment of the present invention, active breaking during the centrifugation process can be done.
[0064] With reference to FIG. 4 , reagent dispenser head 60 is mounted in a positioning mechanism 67 instead of an XYZ-translation frame. Positioning mechanism 67 links a small head positioning motor (a stepper motor similar in form to the rotor motor) via a pivot to a pivot linkage and a suitable bearing mechanism. This positioning motor, through less than 180 degrees of rotation, maneuvers reagent dispenser head 60 such that its array of nozzles (shown schematically as nozzles 65 A1 , 65 C1 , and etc., in FIG. 4 ) match orthogonally to the array of wells 41 A1 , 41 B1 , etc., within microtiter plate 42 as both dispenser head 60 and plate 42 are in constant synchronized motion. A motor shaft 70 is connected to a circular arm 69 that an effective length Ld which measures approximately 5 mm from the center of motor shaft 70 to the center point of a pivot 71 on its opposite end. The motion of this pivot point (Xd, Yd) is described by the formulas:
[0000] Xd =COS (θ)* Ld
[0000] Yd =SIN (θ)* Ld
[0000] where θ is the motor angle and Ld is the length of the arm, as is indicated in FIG. 4 .
[0065] Pivot point 71 is connected to a linear bearing via a linkage arm 74 that translates the rotational motion of the motor and arm into a linear motion, along the Y-axis, as indicated by arrow Y in FIG. 4 , and in line between the central axis of the rotor and dispenser motor's axis of rotation about motor shaft 70 . The location of this linkage pivot point (XI, YI) is determined as follows:
[0000] XI=0
[0000] YI=SQRT (( Lb+Xd )*( Lb−Xd ))
[0000] wherein the X component is constrained to 0; SQRT is to take the square root of ( ) and Lb is the length of the bearing linkage arm.
[0066] Given that correct values are established for the lengths of the various linkage components and the locations for centers of rotation of the head positioning mechanism motor and the rotor assembly, the criteria for establishing alignment between the dispenser nozzle arrays and microtiter wells is aligning the angle of rotation of the rotor to the angle of the linkage arm. This is determined by:
[0000] θ L=A SIN ( Xd/Lb )*(180/π)
[0000] θR=Given by motor commanded position
[0000] Wherein θL is the linkage arm angle in degrees, relative to the linear bearing pivot point; π is the value 3.14159. The location of the A1 nozzle position relative to the bearing pivot point is determined by:
[0000]
Xn=Nv*Xd/Lb
[0000] Yn=YI +( Nv *COS ( A SIN ( Xd/Lb ))
[0000] wherein: Xn is the A1 X-axis nozzle location relative to the bearing pivot; Yn is the A1 Y-axis nozzle location relative to the bearing pivot; Nv is the distance between the A1 axis nozzle location and the bearing pivot point (the hypotenuse of the triangle formed by Xn and Yn).
[0067] The location of well A1 in a microtiter plate within the rotor, in the coordinate system of the dispenser head is determined by:
[0000] Xr =SIN (θ L*π/ 180)* Rv
[0000] Yr=ABS ( Ya −(COS (θ L*π/ 180)* Ya ))+ Ya
[0000] wherein: Xr is the A1 X-axis position relative to the origin at the dispenser drive motor center of rotation; Yr is the A1 Y-axis position relative to the origin at the dispenser drive motor center of rotation; Ya is the measured distance from the rotor center to the center of well A1 along the Y-axis; Rv is the distance between the rotor center point and the A1 well position (The hypotenuse formed by Xr and Yr); and ABS( ) is to take the absolute (non-negative) value of the number evaluated.
[0068] Evaluation of the preceding formulas as a system with variable data provided that reflects the dimensions associated with accommodating eight 384 well microtiter plates (128mm×84 mm) within a rotor of 560 mm diameter yields the motion profiles illustrated in FIG. 5 . The motion of well A1 in a 384 well microtiter plate is illustrated in FIG. 6 .
[0069] In liquid delivery operation, the start point is properly synchronized, as accomplished by using feedback control of plate registration using a laser or other suitable means. For example, in one embodiment of the present invention, an edge detecting diode laser sensor tied to a high speed interrupt input in the motor controller, and the relative velocities of the motors are matched. With reference to FIG. 4 , because a continuous path system is established, the reagent dispenser head 60 may traverse over microtiter plate 42 , with both components in constant motion, such that accurate alignment between the nozzle array and array of microtiter plate wells will exist at nearly regular intervals. During these intervals any one of the dispensing valves, when called upon programmatically from the real time controller, can open and dispense liquid into a corresponding well, and close before the nozzle and the well travel out of alignment. Once a pass over a plate has been made, the head can move back to its start position with a rotation of less than 180 degrees while the rotor continues in the same direction bringing the next microtiter plate toward the position where dispensation can begin for the next microtiter plate. In the case of microtiter plate densities greater than 96 wells, successive passes of the rotor may be made, shifting the dispenser in the Y-axis before the beginning of each pass.
[0070] Advantageously, such a configuration utilizing positioning mechanism 67 increases the efficiency and throughput of a microtiter plate based centrifuge synthesis system and provides for an efficient dispensing configuration on a liquid handling system that utilizes radial geometry for organizing and moving microtiter plates. This embodiment of the present invention provides for a means of continuous liquid addition with respect to synchronized motion of the rotor and dispenser. This embodiment provides for complete orthogonal access to microtiter plates of a rotor assembly utilizing only two drive motors and without motion control algorithms that would be associated with an XYZθ system.
[0071] Although only one reagent dispenser head 60 is illustrated in FIG. 1 , apparatus 40 may be provided with multiple reagent dispenser heads. For example, a second reagent dispenser head may be provided diametrically opposed to bulk fluid dispenser 52 , that is to the right side of support surface 49 as viewed in FIG. 1 . One should appreciate that the apparatus may include one, two, three or more reagent dispenser heads and still fall within the scope of the present invention.
[0072] Additionally, a supplemental reagent dispenser head may be provided to serve as a spare. For example, if one nozzle or one cartridge of reagent dispenser head 60 is malfunctioning, an operator may remove it from translation frame 62 and move it to a maintenance station 80 ( FIG. 1 ). Maintenance station 80 is located above support surface 49 and remote from the other major components of apparatus 40 , namely the rotor assembly and the bulk fluid dispenser. The operator may then disconnect the fluid lines and reconnect the lines to the supplemental regent dispenser head and, in turn, install the supplemental head on translation frame 62 . Accordingly, the apparatus can continue to operate while the malfunctioning dispenser head is serviced, reconditioned, or replaced.
[0073] The reagent dispenser head may take a variety of alternative forms and fall within the scope of the present invention. A variety of delivery techniques for the delivery of reagents to the microtiter plate wells may be used, including inkjet and piezo techniques. For example, the reagent dispenser head of the present invention may include self-contained cartridges. Typically, solutions such as A, C, G, and T bases and activators are prepared in large volumes kept in large containers. This is because the solution must be made fresh and cannot be stored longer than a couple of days. Typically, each solution is prepared with crystalline materials and liquid materials separated from one another. A cartridge in accordance with the present invention similarly includes crystalline and liquid materials separated by suitable means such as a membrane. The cartridge membrane is pierced by suitable means and the materials mix together to form the solution.
[0074] The regent dispenser head and nozzles may include various types of fluid connections. Conventional tubing types are relatively soft and compliant and are not well-suited for harsh organic solvents. In contrast, tubing that is made to withstand harsh organic solvents is generally not soft and compliant, but is rather stiff in nature being more like a plastic than a rubber product. Typically, a small barbed fluid fitting is used in conjunction with a relatively soft and flexible tubing. The tubing generally slips over a barbed end and stretches to create a seal at the edge of barb, provided that the tubing is sized correctly to the barbed fitting.
[0075] In a preferred embodiment, a barbed fitting 90 ( FIGS. 7( a ) and 7 ( b )) of the present invention has a fluid interface that is not dependent upon conventional soft tubing. Instead, a “quick-connect” barbed fitting utilizes a spring loaded collar force to provide a compression fit around the end of the fitting. See FIG. 7( a ). In particular, the fluid delivery system of the present invention utilizes a TEFLON® fitting or port 91 designed to accept a barbed end 92 of fitting 90 for a certain distance, but not the complete length of barbed end 92 . The port 91 is designed with a chamfer 94 ( FIG. 7( b )) to help guide and center port 91 on a cone shaped barb 95 on barbed end 92 . Barbed end 92 is held in place by a spring 96 that applies a constant pressure to nozzle 65 and barbed end 92 biasing it into TEFLON® port 91 when nozzle 65 is inserted into cartridge 66 ( FIG. 1) This configuration provides a constant pressure which maintains barbed end 92 within port 91 because the constant pressure is greater than any internal fluid pressure that will be generated within the reagent delivery system, which is generally less than 10 psi and preferably approximately 3 psi. Because the TEFLON® has a low hardness, TEFLON® port 91 deforms slightly and conforms to the shape and angle of barbed end 92 . Over time the TEFLON® will creep slightly and, because the spring is applying constant pressure, will maintain and even improve the seal of barbed fitting 90 . Advantageously, this configuration offers greater ease of assembly and disassembly. An operator merely needs to compress spring 96 and pull barbed end 92 out of TEFLON® port 92 to disconnect the fitting removing guide members 97 from alignment holes in cartridge 66 ( FIG. 1 ) and remove nozzle 65 from the cartridge. To replace nozzle 65 , an operator merely needs to insert nozzle end 98 into a corresponding nozzle aperture in cartridge 66 , compress spring 96 , and then align guide members 97 with corresponding alignment holes in cartridge 66 .
[0076] The barbed fitting of the present invention is purely suited for connecting a barbed type tube coupler to a manifold or other fluid handling device without using flexible tubing. Such a configuration also promotes simplified manifold design suitable for micro-fluid applications that require valves having a barbed fitting. Furthermore, such as configuration allows barbed fittings to be used in applications which utilize harsh solvents.
[0077] Turning now to centrifugation and liquid removal, a rotor assembly typically is activated to centrifugate microtiter plates in a fixed angle with respect to the rotor and with respect to vertical. Precise separations may be achieved by controlling the amounts of liquids, the angle of the microtiter plate, the speed, and the duration of rotation. Previous centrifugal synthesizers utilized rotor that held microtiter plates at a fixed angle, as is described in U.S. Pat. No. 6,045,755 to Lebl et al., the entire contents of which is incorporated by this reference. In contrast, rotor assembly 46 of the present invention dynamically alters the angle of microtiter plate 42 during centrifugation. Rotor assembly 46 allows the angle of microtiter plate 42 to dynamically adjust between different synthesis processes but maintains microtiter plate 42 at a fixed, substantially horizontal position with respect to rotor assembly 46 as fluids are dispensed into wells 41 of microtiter plates during process cycles.
[0078] In one embodiment of the present invention, rotor assembly 46 includes a rotor 47 and a plate holder 101 ( FIG. 2 ). Preferably rotor 47 is formed of a composite material, for example carbon fiber. Carbon fiber rotor 47 in accordance with the present invention is advantageous in that it is light weight, easy to balance and requires little maintenance. Such a carbon fiber rotor will not warp and thus will minimize the need for periodic balancing thereof. One should appreciate that the rotor can be made of other suitable materials such as metal and plastic.
[0079] Plate holder 101 ( FIG. 2 ) is configured to dynamically alter the relative angle of microtiter plate 42 with respect to rotor 47 . In particular, with reference to FIGS. 8( a ) and 8 ( b ), plate holder 101 is pivotally mounted on rotor assembly 46 by a pivotal support 102 located at an outer end 103 of the plate holder remote to the centrifugal axis of rotor assembly 46 . Microtiter plate 42 is selectively engaged with plate holder 101 by a spring-biased latch mechanism 104 .
[0080] A biasing mechanism 105 supports an inner end 106 of the plate holder with respect to rotor 47 intermediate pivotal support 102 and the centrifugal axis of the rotor assembly. Biasing member 105 includes a biasing spring 107 and an adjustable stop member 108 . Biasing spring 107 biases plate holder 101 and microtiter plate 42 in a horizontal position against rotor 47 while the rotor assembly is stationary or moving slowly. Accordingly, microtiter plate 42 is in a horizontal position when reagent dispenser 52 is addressing the array of wells 41 on microtiter plate 42 . Stop member 108 is adjustable such that the predetermined desired angle of tilt can be adjusted as necessary. In the embodiment shown in FIG. 8( b ), inner end 106 serves as a hard stop against rotor 47 . One should appreciate that an adjustable hard stop can be provided in order to provide means for finely adjusting the horizontal position of plate holder 101 . Similarly, biasing mechanism 105 biases plate holder 101 against rotor assembly 46 into the horizontal position as rotor 47 decelerates.
[0081] When rotor assembly 46 is activated and begins to rotate, microtiter plates 42 increasingly tilt against the biasing force of spring 107 as centrifugal forces increase until plate holder 101 and microtiter plate 42 reach a desired predetermined angle. To accomplish this, the effect of increasing centrifugal force is utilized to move plate holder 101 and microtiter plate 42 to the desired angle. Specifically, a counter weight 109 is provided on outer end 103 at a location below pivotal support 102 . As centrifugal forces on counter weight 109 increase and overcome the biasing force of spring 107 , plate holder 101 and microtiter plate 42 tend to rotate about pivotal support 102 as shown in FIG. 8( b ). In particular, as rotor 47 accelerates during centrifugation the centrifugal forces acting upon the combined centers of gravity of plate holder 101 and microtiter plate 40 overcome the force of gravity and the force of in the biasing mechanism 105 .
[0082] One should appreciate that other suitable biasing mechanisms may be used for biasing plate holder 101 to horizontal position. For example, coil springs, torsion springs, leaf springs, and even gravity may be used for biasing plate holder 101 against rotor 47 . An alternative biasing mechanism 111 is shown in FIG. 9 and is located on a central portion of rotor 47 adjacent the centrifugal axis. Biasing mechanism includes a biasing arm 112 connected to plate holder 101 by tension cable 113 . Biasing arm 112 is biased toward a neutral position by torsion spring 114 . As centrifugal forces increase, plate holder 101 begins to tilt and pulls on cable 113 and against the torsion force of torsion spring 112 thus moving arm 112 toward an adjustable stop bracket 115 . Stop bracket 115 is easily adjusted by loosening a locking screw 116 and rotating stop bracket to a desired position which in turn adjusts the predetermined desired angle of plate holder 101 and microtiter plate 42 .
[0083] Advantageously, the biasing mechanism of present invention provides a simple means which allows the delivery of liquid to microtiter plates within the rotor to take place with the microtiter plate in a horizontal position. This feature becomes increasingly important as well densities increase; that is, as the number of wells on a microtiter plate increase. This feature also become increasingly important as the diameter of the wells decrease and when liquid delivery takes place while either the microtiter plate or the reagent dispenser head is in motion. Since the plate is horizontal and thus normal to the array of nozzles during liquid delivery maximum target area of the wells is presented to the dispenser array. Advantageously, the biasing mechanism of the present invention also allows facile adjustment of the microtiter plate angle for dispensing cycles. The biasing mechanism allows easy access to the spring tension mechanism without removing the rotor from the apparatus.
[0084] In another embodiment of the present invention, the reaction vessel or well is formed of a porous polymeric material. It is commonly known that filtration may be used to separate liquids from a wetted substrate. Commonly, filtration is typically accomplished by centrifugation of the liquid through a discrete filter mesh or frit which is located at the bottom of a well or column in which oligonucleotide synthesis takes place. In one embodiment shown in FIG. 10( a ), microtiter plate 121 and the array of wells 122 therein are formed of a porous polymeric material. Examples of suitable materials are TEFLON®, polyethylene, polypropylene and KYNAR®. Such porous polymeric materials are typically available in sheets, rods, tubes, and molded shapes. Such materials can be machined while maintaining its porous quality as long as the surface temperature of the material during machining does not reach the melting point of the material. One should appreciate that the shape of wells 122 may vary depending on the particular application and/or desired fluid dynamics. For example, the depth and diameter of the porous well may be U-shaped, V-shaped, or flat bottomed. Furthermore, the side wall of the well may be cylindrical, conically shaped, flat, tapered inwardly or outwardly, or have any other desired geometry. One should also appreciate that the shape of the microtiter plate itself may also vary. For example, instead of having a planar rectangular shape, the plate may include a planar surface having an arcuate shape, a triangular shape, or any other geometric shape as viewed from above depending upon the design of the rotor assembly.
[0085] Porosity of the material typically depends on the specific material and can be as low as 7 μm. Any such material can be used as long as the porosity is less than the maximum physical dimension of a substrate. For example, any material can be used for organic synthesis of oligomers as long as the porosity is less than the dimension of solid-phase particles such as a microbeads used in the synthesis. Alternatively, in the event that a discrete solid-phase particle is not used and the microtiter plate itself is used as the substrate, any porous polymeric material can be used as long as the porosity supports the liquid under the normal force of gravity but does not support the liquid under the higher forces of centrifugation.
[0086] One should appreciate that oligonucleotides can be synthesized not only in a microtiter plate having an array of wells, but may be synthesized in a porous rotor 123 ( FIG. 10( b )) having a circumferential array of integral porous wells 124 , or in a porous individual well 125 ( FIG. 10( c )). The porous wells of the present invention beneficially reduces the complexity of filtration-based oligonucleotide synthesizers and provide an inherently simple tool for high-throughput synthesis of oligonucleotide. Not only do porous wells reduce the number of components of the rotor assembly, they also simplify maintenance of the rotor assemblies. Furthermore, porous wells in accordance with the present invention reduce rotor inertia intricacies of centrifugal synthesizers and therefore reduce cycle time. The porous wells of the present invention also increase the efficiency of “spill-over” based central synthesizers by decreasing the drying time required between sequential substrate exposures. Porous polymeric wells can also be reused for multiple synthesis in which radiation, thermal, chemical or other purification techniques are used to cleanse the wells. For example, the wells can be chemically purified by using a muriatic acid and water solution.
[0087] The porous wells in accordance with the present invention are particularly suited for reducing the complexity of filtration-based oligonucleotide synthesizers. The porous wells provide a simple means of simultaneous filtering of numerous wells, which promotes simplicity, efficiency, and high-throughput. Porous wells can also be used for proficient chemical labeling and/or modifying of oligonucleotide.
[0088] Alternatively, filtration, as well as reagent delivery, can be accomplished through frits on top of the microtiter well using centrifugation. In one embodiment of the present invention, a mesh 126 ( FIG. 11( a )) is used to retain microbeads 127 in the wells. Mesh 126 or frit material can be placed over well 41 during centrifugation. Alternatively, mesh 126 can be used as the base of each well, as noted above. In either case, the use of mesh 126 during centrifugation retains beads 127 in the well, and therefore obviates the need for tilting the wells and/or microtiter plate at a critical angle of centrifugation because mesh 126 is fine enough to retain the beads but is sufficiently porous to allow the passage of liquids therethrough in the same manner as the porous polymeric material discussed above. Mesh 126 advantageously allows spent reaction liquid or washing solvents to be removed efficiently and completely. Also, very small quantities of microbeads 127 can be used without risk of loss. This allows smaller well volumes and thus higher well density, that is more wells per unit area of plate. This allows higher throughput and the ability to simultaneously synthesize a greater number of different compounds. Placement of mesh 126 above beads 127 allows a further level of control during reagent deliver because the reagents can be dispensed in bulk to all the wells, then delivered synchronously by centrifugation of wells 41 and causing the reagents to pass through mesh 126 of all wells simultaneously.
[0089] In operation and with reference to FIGS. 11( a )-( d ), wells 41 of a microtiter plate (not shown in FIGS. 11( a )-( d )) contain beads 127 and a retaining mesh 126 . Mesh 126 is shown recessed in well 41 , however, one should appreciate that mesh 126 can alternatively be placed on top of well 41 and/or be used as the base of well 41 . Liquid is then delivered to well 41 . Because mesh is sufficiently fine, the liquid does not penetrate mesh 127 and enter into well 41 under the force of normal gravity. The liquid does not penetrate mesh 127 and enter well 41 until centrifugation is begun. The direction of the centrifugal force, indicated by arrow CF causes the liquid the pass through mesh and enter well 41 at which time reaction begins within the well. Liquid is expelled by reversing the direction of the centrifugal force as indicated by arrow CF′ shown in FIG. 11( d ). This may be accomplished by simply reversing the orientation of the well with respect to the rotor.
[0090] In another embodiment of the present invention, mesh 126 is provided at the base of well 41 , as shown in FIGS. 12( a )-( b ). In this embodiment, because the mesh is sufficiently fine, the liquid does not penetrate mesh 128 and exit well 41 through aperture 129 under the force of normal gravity. The liquid does penetrate mesh 128 and exit well 41 through aperture 129 under the force of centrifugation as expelled liquid indicated by arrow EL in FIG. 12( b ). Similar to the above embodiment, mesh 128 retains the beads while liquid is expelled from well 41 by centrifugation. The use of mesh 128 also removes the need for a critical angle of centrifugation.
[0091] In yet another embodiment of the present invention, a less fine mesh 131 which does not impede the flow of liquid therethrough but is sufficiently fine to prevent microbeads 127 from passing therethrough is provided at the bottom of well 41 , as shown in FIG. 13 . Because mesh 131 does not retain liquid within the well, a sealing means 132 in the form of a biased seal or plug is provided to close aperture 133 . A spring 134 is provided which biases sealing means against aperture 133 and when the rotor assembly is moving slowly or at rest. As centrifugation begins, the centrifugal forces acting on the liquid and the mass of the sealing means 132 overcome the biasing force of spring 134 and cause the sealing means to move away from the well thereby opening aperture 133 and allowing liquid to exit well 41 . This configuration also obviates the need for tilted microtiter plates and the need for a critical angle of centrifugation.
[0092] Turning now to the control mechanism, a variety of different control mechanisms are used in synthetic reactions accordance with present invention. The present invention is adaptable to controls requiring manual intervention for some, or even all, processing steps of oligonucleotide (or other polymer) synthesis. The apparatus of the present invention is also adaptable to semi-automatic or fully-automatic controllers. Automatic control mechanisms should be sufficiently general that a different final compound can be synthesized in each reaction vessel or well of each array of wells utilized by the apparatus, and that a different combinatorial synthesis protocol can be performed each well and/or sets of wells. Finally, the automatic controller should be able to manage a plurality of wells, arrays of wells, fluid dispensers, rotor assemblies, and other work stations and subassemblies such that all components of the apparatus are optimally engaged or performing tasks for the synthesis.
[0093] The automatic control mechanisms are supported by certain hardware and software elements. General hardware elements preferably include one or more general control computers, an optional number of specialized control processors, and electrical interfaces to all controlled components of the apparatus. In a manner known in the art, all the directly and indirectly controlled components of the apparatus can be provided with electrical interfaces having certain standardized electrical characteristics. Certain of these low-level hardware interfaces are directly linked from their standardized interfaces to interfaces of the general control computers. Optionally, for complex resources, such as complex work stations, an intermediate level of specialized control processors is interposed between the general control computers and the low-level electrical interfaces of such resources.
[0094] The general control computers can be sufficiently capable personal computers (PC's) provided with such specialized electrical interfaces. An exemplary personal computer includes an Intel PENTIUM® processor running at 133 MHz, a 1 gigabyte or greater hard drive, 16 megabytes or more of memory, and commercially available interface boards providing interfaces such as D/A or on/off output circuits or links to standard instrument control buses. Specialized CPU's on custom PC boards for valve control, for example, an INTEL® 8051 compatible microprocessor, or other commercial motion control systems, for example, a COMPUMOTOR® 6K2, can be for low level control in accordance with the present invention. A PC running LINUX® and a custom designed control application (high level control) can be used to communicate with and control the low level controllers via ethernet and serial (e.g., RS-232) lines in accordance with the present invention. One should appreciate that such hardware control elements can be directly accessed or indirectly accessed via suitable internet or Intranet connection.
[0095] General software elements executed by the general control computers include operating system software, low-level moment-to-moment control and monitoring software, scheduling and monitoring software, and synthesis planning software. At the lowest software level is the operating system software of the general control computers, which in an exemplary embodiment, can be UNIX® or WINDOWS NT® (Microsoft Corporation). The low-level moment-to-moment control and monitoring software inputs scripts describing in detail actions to perform and outputs electrical control signals to the controlled processing resources through the interfaces attached to the general control computers. These signals cause work station actions to be performed. At the next software level is scheduling software, which inputs a description of the synthetic steps to be performed, the locations of stored building blocks and reagents, the location and type of available work stations, the location and type of available interchangeable tools, and so forth, and outputs the detailed command scripts controlling subassembly functions. These scripts are interpreted by the moment-to-moment control and monitoring software. At the highest software level is chemical synthesis planning software, which inputs a description of the synthetic protocols available in a particular embodiment of the apparatus and the desired compounds to be synthesized, and then outputs the synthetic steps necessary to synthesize the desired compounds in a form usable by the scheduling software.
[0096] Various feedback controllers can be utilized to optimize the efficiency of oligonucleotide synthesizers in accordance with the present invention. For example, a plate reader 138 ( FIG. 1 ) is provided on support surface 49 for real time monitoring of the chemical reactions in the wells during synthesis. In one embodiment of the present invention, plate reader 138 is an RS-170 color camera and frame grabber. Wetness monitors 139 are provided within support enclosure 45 in order to monitor leakage of the various liquids within the enclosure and thereby minimize down-time for maintenance and repair necessitated by leakage. Actuation of collection may also be employed in order to collect waste in an efficient manner in order to minimize waste disposal costs and/or promote recycling. For example, a two-way valve 141 is fluidly connected to a drum 142 which surrounds rotor assembly 46 for collecting liquid that is expelled from wells 41 during centrifugation. Two-way valve 141 selectively couples drum 142 with either a solvent catch basin 144 or a spent reaction fluid catch basin 145 . In this manner, the liquids used during different synthesis processes, namely the addition and separation process and the washing process, are readily separated from one another.
[0097] In another embodiment of the present invention, an apparatus 150 ( FIG. 14 ) is particularly suitable for use by individual users. Typical DNA synthesizers used in laboratories are relatively large, have a low capacity (for example only 4 to 16 oligonucleotides are made per run), are not fully automated, and require considerable attention. As a result, it is more cost-effective and time-efficient from the small labs to outsource oligonucleotide synthesis and manufacture. In contrast apparatus 150 is a compact oligonucleotide synthesizer, also referred to as a personal synthesizer, which has a very small footprint, is fully automated, and requires little or no attention during a run. Apparatus 150 is more cost-effective than outsourcing at present costs and can provide a quicker turned-round of small-scale synthesis and is particularly suited for high throughput, multi-protocol combinatorial syntheses. Furthermore, apparatus 150 has a small footprint and thus maximizes lab-top space. Apparatus 150 is adapted for synthesizing oligomers in each of a plurality of reaction vessels which are disposed in circular arrays, such as the circumferential array of reaction vessels or wells 122 ( FIG. 10( b )). Apparatus 150 generally includes a support enclosure 155 , a rotor assembly 123 ( FIG. 10( b )) for supporting one or more wells 122 , and a liquid delivery head 157 . Support enclosure 155 provides mechanical support for the rotor assembly and liquid delivery head 15 . The support enclosure 155 illustrated in FIG. 14 is approximately the same size as a desk-top printer. One should appreciate that the dimensions the personal synthesizer may vary.
[0098] Rotor assembly 123 is rotatably supported by support enclosure 155 and rotates about a centrifugal axis 158 which extends substantially orthogonal to the rotor assembly as wells as the desk-top or support surface upon which apparatus 150 is placed. Liquid delivery head 157 is a multi-channel dispenser including one or more solenoid valves 161 circumferentially spaced about centrifugal axis 158 and disposed concentrically with respect to the rotor assembly 123 . Liquid delivery head is capable of simultaneously delivering a plurality of different liquids to corresponding different sets of wells 122 of the rotor assembly. Although ten solenoid valves 161 are shown, one should appreciate that one, two, three, or more valves may be provided depending upon the particular number of channels desired. Solenoid valves 161 are circumferentially spaced about a diameter which is substantially equal or approximate to the diameter of the circumferentially disposed wells 122 of rotor assembly 123 . Accordingly, the dispensing nozzles associated with solenoid valves 161 are suspended in a circular pattern above wells 122 in the rotor assembly. The centrifugal motor which drives the rotor is capable of high acceleration and deceleration rates, velocities up to 4000 RPM, and positioning resolution of +/−0.2 degrees. Accordingly, specific ones of wells 122 can easily be aligned with any one of the dispensing nozzles.
[0099] Rotor 123 ( FIG. 10( b )) of apparatus 150 can be configured to be a single-use and disposable item. Similarly, solenoid valves can self-contained and disposable cartridges which contain reagents, activators, and/or solvents. This embodiment combines the concept of the centrifuge synthesizer with the concept of a self-contained disposable liquid cartridge. The disposable liquid cartridge concept is similar to that employed in the field of desktop inkjet printers. This combination it is possible to produce a personal oligonucleotide synthesizer, a small low-cost, easy-to-operate, and highly automated device that can easily be programmed to perform custom synthesis of oligonucleotides as well as other molecules. In the event that self-contained, disposable cartridges are used, an operator of apparatus 150 does not have to weight, mix, and/or otherwise prepare reagents for use with apparatus 150 . Instead, the operator simply inserts one or more cartridges in delivery head 157 which then automatically delivers controlled quantities of reagents to defined locations under computer control. The particular delivery pattern or delivery sequence of particular reagents determines the actual composition of the oligonucleotide being synthesized, much like the spatter or delivery of droplets of ink determines the content of a page printed by an inkjet printer.
[0100] One significant difference between the present invention and an inkjet printers is that inkjet printers typically use a small set of inks, for example black, red, blue, and yellow. The personal oligonucleotide synthesizer of the present invention is configured to receive a number of different reagent cartridges, thus allowing the synthesis of various molecules. For example, personal synthesizer 150 is provided with a plurality of different cartridges for various DNA reagents, RNA reagents, peptide reagents, fluorescent dyes and/or other chemical materials.
[0101] The personal oligonucleotide synthesizer 150 has a small rotor capable of up to 96 synthesis procedures at one time because it includes 96 concentrically spaced wells. One should appreciate that lesser or greater capacities can be incorporated depending upon the number of wells provided. Reaction wells 122 of rotor 123 may be arranged in a single circle (not shown) or in concentric circles of wells 122 , 122 ′ ( FIG. 10( b )) in order to increase the capacity of both the rotor and the personal synthesizer 150 . On should also appreciate that the rotor can be configured to receive curved microtiter plates 163 as is shown in FIG. 15 . The curved microtiter plates are selectively secured to the rotor assembly by suitable means such as a spring biased latch. In any event, solid-phase support is contained within the wells of the rotor in the form of microbeads, or other suitable solids, in a similar manner to that discussed above. Alternatively, a derivatized membrane may be used within the wells instead of and/or in addition to the microbeads.
[0102] As shown in FIG. 14 , apparatus 150 includes an array of the nozzles that is arranged radially along the perimeter of the rotor assembly which significantly simplifies the process of addition and removing liquids from wells 122 . In fact, delivery head 157 can deliver liquid to wells 122 while the rotor is still moving in a similar manner as discussed above. Discrete high-speed control of solenoid valves 161 are controlled dependant upon, pressure, time, volume, and the speed at which rotor assembly 123 is moving. Such a configuration allows the liquid delivery head to deliver liquid to all the wells located in the rotor assembly in approximately 8 to 10 seconds.
[0103] In the case the personal synthetizer is provided with a rotor having two or more concentric arrays of wells, a spiral translation mechanism 163 ( FIG. 16 ) would be incorporated into liquid delivery head 157 in order to adjustably support the dispensing nozzles 164 . Spiral translation mechanism 164 includes two circular structures, one static disc 165 and one dynamic disc 166 . Static disc 165 contains slots 168 running from its center toward its periphery in a radial pattern. Slots 168 are wide enough to slidably accommodate dispensing nozzles 164 along a radial path. Dynamic disc 166 includes an identical number of curved slots 168 milled to approximately the same width also running from the central portion of dynamic disc 166 to the periphery thereof in a arcuate path. Static disc 165 and dynamic disc 166 are concentrically and rotatably mounted with respect to the other. Nozzles 164 are mounted substantially vertically within the slots at each point where the path of a straight slot 168 crosses the path of a curved slot 169 . When static disc 165 and dynamic disc 166 are rotated relative to one another, nozzles 164 moved directly along the path of the straight slots 168 . This configuration this allows precise synchronized control of the nozzle locations about the central axis. Dynamic disc 166 can be controlled by an actuator such as a stepper motor, air cylinder, rack and pinion structure, rotor-drive stepper motor, or any other suitable means.
[0104] Apparatus includes a locking actuator, for example an air cylinder plunger 171 schematically shown in FIG. 16( a ), which is mounted on dynamic disc 166 over the center of rotor assembly 123 . Actuator 171 would extend downwardly toward the top of rotor assembly 123 . Actuator 171 includes a non-rotating shaft. The end of the shaft selectively engages the top of rotor assembly 123 . Actuator 171 also contains a brake which is engaged with static disk 165 whenever actuator 171 is not actuated thereby holding the nozzle array in a set position. When relocation of the nozzle array is desired, rotor assembly 123 stops in alignment with actuator 171 because the particular position is remembered from the last operation. Actuator 171 is actuated and it engages rotor assembly 123 and disengages the brake. Rotor assembly 123 rotates to a position that is supplied from a lookup data table stored in control software. Actuator 171 disengages from rotor assembly 123 and reengages the brake. The system is now ready to access the next array of wells. This process control allows location of the concentric ring of nozzles about the center and supports dispensing to multiple concentric rings of wells within rotor assembly 123 .
[0105] Apparatus 150 may also use a variety of different control mechanisms in accordance with present invention. The present invention is adaptable to controls requiring manual intervention for certain, or even all, processing steps of oligonucleotide synthesis. The apparatus of the present invention is also adaptable to semi-automatic or fully-automatic controllers which are run by personal computers. In one embodiment of the present invention, personal synthesizer 150 is controlled by a PC or with a hand held personal computing device which synchronize with a PC. In the case of the latter, an infrared port 174 ( FIG. 14 ) is provided on support enclosure 155 thus allowing an operator to synchronize data and otherwise check the status of the personal synthesizer. Preferably, basic parameters will be displayed directly on the personal synthesizer or readily displayed on the personal computing device in order to minimize the need of a PC in the vicinity of the personal synthesizer and thereby free up critical lab-top workspace.
[0106] One disadvantage associated with conventional oligonucleotide synthesis is scaling the technology to increase numbers. An apparatus 180 ( FIG. 17( a )) in accordance with a present invention allows a large number of oligonucleotides to be synthesized easily and cost effectively. Apparatus 180 includes a support mechanism 181 which rotatably supports a plurality of microtiter plates 42 . Specifically, mechanism 181 is capable of holding microtiter plates 42 in either an upright or an inverted position. When plates 42 are an upright position, reagent dispensing head 182 addresses plates 42 and delivers individual reagents into the wells of plates 42 . When plates 42 are in an inverted position, the plates can be washed with the appropriate reagents dispensed by wash head 183 . This configuration creates an effective format delivering reagents and washing the plates, typically the most difficult and time-consuming step in the process. Mechanism 181 may include a conveyor belt 184 , a chain drive system, an axes driven system 185 ( FIG. 17( b )), or any other suitable drive system for translating and inverting the microtiter plates.
[0107] Advantageously, apparatus 180 provides a high-throughput chemical synthesis instrument which may be used for oligonucleotide synthesis. Because microtiter plates 42 are conveniently inverted for washing, the apparatus creates a physical dimension that is independent from the dimension used for base addition.
[0108] Microtiter plates 42 are derivatized to allow base addition therein. As this is accomplished by derivatizing commercially available plates with an amine or an —OH functionality.
[0109] The foregoing descriptions of specific embodiments of the present invention have been presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the invention to the precise forms disclosed, and obviously many modifications and variations are possible in light of the above teaching. The embodiments were chosen and described in order to best explain the principles of the invention and its practical application, to thereby enable others skilled in the art to best utilize the invention and various embodiments with various modifications as are suited to the particular use contemplated. It is intended that the scope of the invention be defined by the Claims appended hereto and their equivalents. | An apparatus for high-throughput combinatorial synthesis of organic molecules including a reaction vessel for containing a combinatorial chemistry synthetic reaction, a liquid dispenser for dispensing the liquid, a liquid aspirator and an adjustment mechanism. The reaction vessel includes an ingress aperture allowing a liquid to enter into an interior of the vessel and an egress aperture for aspirating the liquid from the vessel. The liquid dispenser dispenses liquid through the ingress aperture. The liquid aspirator aspirates liquid through the egress aperture and includes a rotor for carrying the vessel and orbiting the vessel about an axis of rotation. The rotor is oriented generally in a horizontal plane and includes an adjustment mechanism for adjusting the angle of the vessel relative to the horizontal plane in response to the centrifugal force generated by orbiting the vessel about the axis or rotation. A method of combinatorial synthesis of organic molecules is also disclosed. | 1 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. patent application Ser. No. 61/593,132, filed on Jan. 31, 2012 which is hereby incorporated by reference in its entirety.
FIELD
[0002] The present invention generally relates to systems and methods for inductive power transfer (IPT) to commutate a linear synchronous motor (LSM) for propelling a vehicle such as a train.
BACKGROUND
[0003] In the railroad industry, one may consider using linear synchronous motors (LSM) to propel rail vehicles. An LSM provides the efficiency and environmental benefits of electric versus diesel locomotives. There is a need for reduced power on-board the vehicle to power brakes, control systems, heating, air-conditioning lighting and passenger convenience (“hotel” power) without relying upon a live third rail or overhead, catenary wires. There is a requirement to provide a position signal that can be used to commutate the windings of the LSM. There is a further need to determine the position of the vehicle more precisely on the track.
SUMMARY
[0004] Various implementations of systems, methods and devices within the scope of the appended claims each have several aspects, no single one of which is solely responsible for the desirable attributes described herein. Without limiting the scope of the appended claims, some prominent features are described herein.
[0005] Details of one or more implementations of the subject matter described in this specification are set forth in the accompanying drawings and the description below. Other features, aspects, and advantages will become apparent from the description, the drawings, and the claims. Note that the relative dimensions of the following figures may not be drawn to scale.
[0006] In one embodiment, the invention provides a system for determining a position of a moving vehicle. The system comprises a plurality of receivers configured to receive inductive power from an inductive power source. The plurality of receivers is further configured to deliver electric power to a power storage unit. The system further comprises a controller configured to determine a position of the vehicle relative to a position of the inductive power source based on position information derived from the inductive power received at the plurality of receivers and based on acceleration of the vehicle.
[0007] In another embodiment, the invention provides a method of determining a position of a moving vehicle. The method comprises receiving at a plurality of receivers inductive power from an inductive power source. The method further comprises determining a position of the vehicle relative to a position of an inductive power source based on position information derived from the inductive power received at the plurality of receivers and based on acceleration of the vehicle.
[0008] In another embodiment, the invention provides a system for determining a position of a moving vehicle. The system comprises means for means for receiving at a plurality of receivers inductive power from an inductive power source. The system further comprises means for determining a position of the vehicle relative to a position of an inductive power source based on position information derived from the inductive power received at the plurality of receivers and based on acceleration of the vehicle.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] FIG. 1 is a simplified illustration of a vehicle on a track powered by a linear synchronous motor with power inductively coupled to the vehicle. An on-board controller combines data from an inertial sensor along with measurements from the inductive power transfer (IPT) windings to determine position, which is communicated via a radio link to a wayside controller, which controls the three-phase linear synchronous motor (LSM) inverter and the single-phase inductive power transfer inverter.
[0010] FIG. 2 . is a simplified illustration of the primary and secondary windings used for inductive power transfer.
[0011] FIG. 3 shows the fixed spatial relationship between the LSM and IPT primary windings.
[0012] FIG. 4 is a simplified schematic of the transfer of power by inductive coupling in order to power on-board devices.
[0013] FIG. 5 is a block diagram of the algorithm used to measure the phase angle of the vehicle relative to the IPT primary windings.
[0014] FIG. 6 is a block diagram of the 3rd order state estimator that is used to combine inertial measurements with phase measurements in order to derive estimates of vehicle position, velocity and motor phase angle.
[0015] FIG. 7 . is a block diagram of the radio link used to transfer data from the on-board controller to the wayside controller where it is used to commutate the LSM inverter, control vehicle position and velocity and manage on-board battery voltage.
[0016] FIG. 8 is a simplified plan view of a track with LSM and IPT windings and RFID tags spaced intermittently along the track.
[0017] FIG. 9 is a graph showing exemplary errors associated with an inertial sensor such as an accelerometer as a function of frequency.
[0018] FIG. 10 is a Bode diagram plot of the response of the state estimator output Estimated Position to the two sensors: Measured Theta derived from the IPT windings, and the inertial sensor.
[0019] FIG. 11 is a flowchart depicting an exemplary process for determining the motion of a moving vehicle.
[0020] The various features illustrated in the drawings may not be drawn to scale. Accordingly, the dimensions of the various features may be arbitrarily expanded or reduced for clarity. In addition, some of the drawings may not depict all of the components of a given system, method or device. Finally, like reference numerals may be used to denote like features throughout the specification and figures.
DETAILED DESCRIPTION
[0021] The following detailed description is directed to certain specific aspects of the disclosure. However, the disclosure may be embodied in a multitude of different ways, for example, as defined and covered by the claims. It should be apparent that the aspects herein may be embodied in a wide variety of forms and that any specific structure, function, or both being disclosed herein is merely representative. Based on the teachings herein one skilled in the art should appreciate that an aspect disclosed herein may be implemented independently of any other aspects and that two or more of these aspects may be combined in various ways. For example, an apparatus may be implemented or a method may be practiced using any number of the aspects set forth herein. In addition, such an apparatus may be implemented or such a method may be practiced using other structure, functionality, or structure and functionality in addition to or other than one or more of the aspects set forth herein. Similarly, methods disclosed herein may be performed by one or more computer processors configured to execute instructions retrieved from a computer-readable storage medium. A computer-readable storage medium stores information, such as data or instructions, for some interval of time, such that the information may be read by a computer during that interval of time. Examples of computer-readable storage media are memory, such as random access memory (RAM), and storage, such as hard drives, optical discs, flash memory, floppy disks, magnetic tape, paper tape, and punch cards.
[0022] FIG. 1 is a simplified illustration of a vehicle 10 on a rail 9 (also referred to as a track 9 ) powered by a linear synchronous motor with power inductively coupled to the vehicle 10 . Since the windings for the linear synchronous motor (LSM) 8 are fixed to the rail 9 , the power to propel the vehicle 10 remains at the wayside. An on-board controller 13 may combine data from an inertial sensor 14 with measurements from the inductive power transfer (IPT) windings 1 to determine position, which may be communicated via a radio (e.g., RF) link 15 to a wayside controller 11 , which controls the three-phase LSM inverter 6 and the single-phase inductive power transfer inverter 5 . To communicate with a receiver (e.g., radio link 12 ), the radio link 15 may utilize any wireless communication link, such as a FM (VHF) link, a mobile/cellular network, a dedicated link or a public network such as the Internet, etc. In one embodiment, the inertial sensor 14 produces an output comprising three respective accelerometer components (or measurements) along the X, Y, and Z axes. Typically, the x-axis is a direction along the direction of travel of the vehicle (e.g., direction of track), the y-axis is a direction perpendicular to both the direction of travel of the vehicle and the direction of gravity, and the z-axis is a direction along the direction of gravity (e.g., vertical axis).
[0023] The vehicle 10 may be fitted with a periodic array of magnets 16 which may be a Halbach array. The magnet array may produce a magnetic flux pattern that is substantially directed below the vehicle 10 towards the rail 9 . The flux pattern has characteristic spatial period with characteristic wavelength denoted by λ LSM .
[0024] Inductive power transfer (IPT) provides a means to couple power from wayside of a rail 9 to a vehicle 10 without relying on a live third rail or overhead catenary wires. IPT may also be used as a means for wayside-to-train communication. A position signal may be derived from an analysis of the relative phase between inductively coupled secondary windings 4 a, 4 b, and 4 c in order to determine the relative position between the vehicle 10 and primary windings 1 located on the rail 9 . The position signal may be transmitted by a dedicated radio link 15 to wayside inverters that may be used to commutate a linear synchronous motor used for vehicle propulsion. The system may include wayside markers and/or a GPS sensor to provide additional information about the overall position of the vehicle in addition to the relative track-to-vehicle information that is provided by the inductive and inertial sensors.
[0025] In addition to providing a signal that may be used to commutate the LSM windings 8 , there is a need to monitor the vehicle position on the rail 9 in order to selectively power only those sections of rail 9 that lie directly beneath the vehicle 10 . The relative position signal derived from the IPT windings may only determine relative position within a single “wavelength” of the IPT windings. Some additional sensor may be used to determine a coarse position along the rail 9 that may be combined with the high-resolution signal determined from the IPT windings in order to unambiguously determine vehicle position.
[0026] Furthermore, there are sections of rail 9 where the primary IPT windings 1 may be interrupted. At track switches, for example, there may exist breaks in the windings where windings from one section terminate and windings for a new section of rail 9 begin. A system that relies exclusively on the IPT windings for position information may have difficulty crossing switches.
[0027] In one embodiment, the invention provides a means to derive relative position from the phase of the IPT secondary windings ( 4 a, 4 b, 4 c ) and to combine that relative position signal with additional sensors in order to provide a high-resolution position signal that is robust in the presence of anticipated errors. The invention further provides a reliable communication system that may be used to communicate position information from the vehicle 10 to the wayside controller 11 . The invention further provides the ability to augment the relative position signal with additional position information that may unambiguously locate the vehicle 10 on the rail 9 . The resulting position signal may be used to commutate windings of a linear synchronous motor 8 to propel the vehicle/train 10 . The signal may also be used in part of a closed-loop position control scheme for the vehicle/train 10 .
[0028] In one embodiment, a primary inductive power transfer (IPT) winding 1 may be located along the rail 9 in parallel with the linear synchronous motor (LSM) propulsion windings 8 . The IPT winding 1 may lie beside the LSM winding 8 . The primary winding 1 has a spatially distributed pattern in a fixed relationship to the LSM windings 8 . The IPT primary 1 winding may comprise wires forming a figure-eight shape as shown in FIG. 2 where each loop of the figure eight may span a length substantially equal to the period of the LSM winding 8 . Therefore, the complete figure-eight loop of the IPT primary winding 1 may span two wavelengths of the LSM winding 8 .
[0029] The IPT windings 1 may repeat the figure-eight pattern continuously along the length of the rail 9 . The IPT windings 1 may maintain a fixed spatial relationship to the LSM windings 8 . The LSM windings 8 may be placed in a structure, such as a bobbin, that locates the LSM windings 8 in a predetermined spatial pattern. The same bobbin may be extended laterally (perpendicular to the axis of the track) with additional slots into which the IPT primary windings 1 may be placed. Thus, the bobbin may be used to maintain the necessary fixed spatial relationship between the LSM windings 8 and IPT primary windings 1 .
[0030] Block switches 18 may connect sections of IPT windings 1 to a single-phase IPT inverter 5 . The IPT windings 1 may lie beside the LSM windings 8 in the space between the rails of the rail 9 .
[0031] The LSM windings 8 may be located along the rail 9 . Each section of LSM winding 8 may be connected to a 3-phase inverter 6 by block switches 7 . Only those sections of LSM winding 8 located beneath the vehicle 10 are powered at any one time. As the vehicle 10 moves along the rail 9 , successive sections of LSM windings 8 are connected to the LSM inverter 6 as the vehicle 10 enters a section and disconnected as the vehicle 10 leaves a section. AC mains 17 provide power for the LSM inverter 6 and IPT inverter 5 .
[0032] As described above, secondary windings ( 4 a, 4 b, 4 c ) are wound on ferrite cores 3 located on the vehicle 10 . The ferrite cores may span one or more wavelengths of the IPT winding λ IPT . On-board controller 13 may use relative phase voltages from the IPT secondary ( 4 a, 4 b, 4 c ) to determine position of the vehicle 10 relative to the rail 9 . The controller 13 may combine data from an inertial sensor 14 with the data from the secondary windings 4 a, 4 b, and 4 c to improve the precision of the position measurement. A GPS receiver 73 may be used to provide an initial position of the vehicle 10 . An RFID tag reader 74 may provide redundant data that may be used to corroborate the position measurement derived from the GPS and position-sensing algorithm. An on-board radio link 15 may transmit position, velocity and phase angle data to a wayside radio link 12 that is connected to a wayside controller 11 .
[0033] A wayside controller 11 may use data received from the vehicle/train 10 to control the LSM windings 8 . The motor phase angle is used to commutate the three-phase LSM inverter 6 . The position and velocity data may be used to close a position loop from which the current command to the LSM inverter 6 is derived.
[0034] A single-phase inverter 5 located at the wayside may be used to power the IPT primary windings 1 . Switches 18 in the form of solid-state or mechanical relays may be used to selectively connect only a portion of the IPT primary winding 1 to the wayside inverter 5 . A wayside control system 11 may determine which section of IPT winding 1 is to be powered at any time. The LSM controller may use a similar, three-phase inverter 6 and associated switches 7 to power only the section of LSM windings 8 that lie below the vehicle 10 .
[0035] The IPT inverter 5 may drive the primary windings with an AC voltage. An AC frequency in the 20 kHz to 50 kHz range may be used in order to enhance the coupling of energy between the IPT primary 1 and on-board secondary windings 4 a, 4 b, 4 c.
[0036] The secondary winding 4 a, 4 b, 4 c may be formed as a polyphase winding with a spatial period that matches the IPT primary period. The polyphase winding may form a well-known three-phase winding. The secondary winding may include a ferrite core 3 or a core made of, for example, thin laminations of silicon steel in order to enhance magnetic coupling with the primary.
[0037] A demodulation circuit not shown may derive a relative position signal from the magnitude of the voltages on the polyphase windings. A three-phase secondary may produce 3 secondary voltages V a , V b , and V c . The three secondary phase voltages may modulate in time at the primary AC frequency, and exhibit an amplitude envelope that may vary spatially with the relative position of the secondary winding relative to the primary winding. The three voltages may be processed to derive a position signal. The resulting position signal may vary from −π to π (radians) at twice the rate (one-half the period) of the primary winding wavelength. The primary wavelength may be selected to be substantially equal to twice the LSM wavelength. The derived position signal may therefore have the same period as the LSM windings and may be used to commutate the linear synchronous motor (LSM).
[0038] The signal derived from the IPT secondary windings 4 a, 4 b, 4 c may invariably contain some undesirable higher harmonics due to imperfections in the winding geometry and/or non-linearity in the detection electronics. If not corrected, the higher harmonics may affect the motor commutation leading to vibration in the linear synchronous motor and a reduction in motor efficiency.
[0039] An inertial sensor 14 may be used to correct the errors in the inductive power IPT-derived position signal. As noted above, the inertial sensor 14 comprises a multi-axis accelerometer that may be located on the magnet array on the vehicle 10 . In one embodiment, the accelerometer X-axis may be aligned with the fore-aft direction of the vehicle 10 , the Y-axis may be aligned laterally and the Z-axis of the accelerometer may be aligned with the vertical axis. On level ground, the Z axis of the accelerometer may report 1G of acceleration while the X and Y axes should report 0 G (where “G” is the acceleration due to gravity or 9.806 meters/second 2 ). The accelerometer output is integrated twice to produce a position signal. However, the accelerometer may invariably have some slight bias to the output signal that may produce a false indication of 0 G. When integrated twice, the position signal from the accelerometer may tend to increase (or decrease) continuously even when the vehicle 10 is at rest.
[0040] An on-board GPS system 73 may be used to provide an indication of the vehicle location on the rail 9 to a resolution of roughly 5 meters. There are instances where a GPS signal may be unavailable such as in a tunnel or in dense urban areas where building may block reliable reception by the GPS receiver 73 .
[0041] Wayside markers using RFID tags may be used as a redundant system to verify the location of vehicle 10 . Passive RFID tags may be positioned at a pre-determined spacing along the rail 9 : a unique tag every 50 meters, for example. As the vehicle 10 passes over the tag, a reader on the vehicle 10 may interrogate the tag and, based on the unique ID stored in the tag, the exact location of the vehicle may be found by looking up the tag location in a database of previously recorded tag locations. This should corroborate the location determined by the GPS 73 plus accumulated position from the state estimator as shown in FIG. 6 . Some small deviation between tag position and computed position would be considered acceptable, but in the case of a discrepancy greater than a pre-determined limit, the vehicle 10 would be stopped while the source of discrepancy diagnosed.
[0042] In the case where a vehicle/train 10 started from a power off condition in an area without access to reliable GPS data, the vehicle/train 10 would be permitted to travel at a minimum speed for a pre-determined maximum distance until a RFID tag was detected or a GPS signal was received. If no tag was found or GPS signal received, the vehicle/train 10 would be stopped and the problem diagnosed.
[0043] The invention provides redundancy provided by combing multiple sensors. Position derived by integrating an accelerometer may be used to ensure continuous position data even when the inductive power transfer (IPT) signal is momentarily interrupted. Multiple means exist to establish the initial position of the vehicle 10 . Once the initial position is established, the position derived from a state estimator as shown in FIG. 6 may be compared with position derived from the RFID tags as shown in FIG. 8 and any significant discrepancy used to indicate a possible fault condition and bring the vehicle 10 to a safe stop.
[0044] FIG. 2 is a simplified illustration of the IPT primary 1 and IPT secondary windings 4 a, 4 b, 4 c used for inductive power transfer. The primary IPT winding 1 configured in a repeating figure-eight loop with a characteristic period of λ IPT as shown in FIG. 3 . The λ IPT period may be selected to be substantially equal to twice the LSM period λ LSM . The IPT secondary windings 4 a, 4 b, 4 c are located on the vehicle as shown in FIG. 1 . While an air core may be used for the secondary windings 4 a, 4 b, 4 c, ferrite cores 3 may improve coupling of flux between the IPT primary 1 and therefore improve the efficiency of power transferred across the air gap. The IPT secondary 4 a, 4 b, 4 c may be wound in a three-phase winding. Each phase may be wound on a ferrite core 3 . Each core may span an integral number of IPT periods. The 3 ferrite cores are spaced an integer number of IPT periods apart, plus an additional ⅓ or ⅔ periods in order to create a well known three-phase winding. For example, winding 4 b is spaced an integral number plus ⅓ periods from winding 4 a. Winding 4 c is spaced an integral plus ⅔ windings from winding 4 a.
[0045] FIG. 3 shows the fixed spatial relationship between the LSM and IPT primary windings. The period of the IPT winding λ IPT 20 may be selected to be substantially equal to twice the period of the LSM winding λ LSM 19 . The spatial relationship between the LSM and IPT windings may be controlled by winding both windings on a common bobbin whereby the desired phase relationship is maintained by the geometry of the bobbin.
[0046] FIG. 4 is a simplified schematic of the transfer of power from the track to the vehicle by inductive coupling in order to power on-board devices. The IPT primary 1 may be powered by a single-phase inverter 5 that is tuned with a capacitor 21 to resonant at a desired frequency. The frequency may be in the range of 20 to 50 kHz. The IPT primary winding 1 may inductively couple to the polyphase secondary windings 4 a, 4 b, and 4 c. The amount of coupling to the polyphase secondary 4 a, 4 b, and 4 c is related to the relative position of the vehicle to the track. The relative magnitude of the AC voltage on the secondary windings 4 a, 4 b, and 4 c, indicated as V a 28 a, V b 28 b and V c 28 c, is indicative of the relative position of the vehicle to the track.
[0047] Secondary tuning capacitors 22 a, 22 b and 22 c tune the secondary to operate near resonance at the selected frequency of the IPT inverter 5 . A three-phase polyphase rectifier 23 converts the secondary AC voltage 28 a, 28 b, and 28 c to a DC voltage that is filtered by DC link capacitor(s) 24 and may be used to charge battery 25 . The rectifier 23 on the vehicle may rectify the AC signal received on the secondary windings 4 a, 4 b, 4 c and the resulting DC may be used to charge the on-board battery 25 . On-board power 27 may be taken from the battery 25 , possibly through an inverter 26 that converts the DC battery voltage 66 to an AC voltage compatible with on-board equipment.
[0048] The-board inverter 26 converts the DC battery voltage 66 into AC power that may be used to power on-board devices as needed. Note that during brief moments when the transfer of power by the IPT sub-system is interrupted, such as might happen at track switches, power may be maintained on-board by the battery 25 . Thus on-board control systems, vehicle/train communication and similar sensitive devices are not affected by momentary disruptions in inductive power transfer.
[0049] The battery voltage 66 may be measured by the on-board controller 13 as shown in FIG. 1 and sent as part of the data packet to the wayside controller 11 . The wayside controller 11 may use the voltage measurement in a closed loop controller to modulate the amplitude of voltage on the IPT primary winding 1 so as to maintain a desired state of charge in the on-board battery 25 .
[0050] FIG. 5 is a block diagram of the algorithm used to measure the phase angle 41 of the vehicle relative to the IPT primary windings. The algorithm determines the phase relationship of the IPT secondary windings 4 a, 4 b, and 4 c relative to the IPT primary 1 . The 3 secondary voltages V a , V b , and V c are squared by block 30 and summed by block 31 to produce a signal proportional to the instantaneous square of the secondary amplitude. Since the secondary is operating at a frequency preferably in the range of 20 to 50 kHz, the instantaneous output of summer 31 may vary between 0 and the square of the peak secondary voltages 28 a, 28 b, 28 c as shown in FIG. 4 . A low pass filter 32 filters the AC signal to produce a slowly varying signal proportional to the square of the secondary voltage. The secondary amplitude is compared in comparator 34 with a pre-determined minimum threshold voltage 33 in order to detect when the IPT system is momentarily disrupted. A signal V IPT — OK 35 may be used in the state estimator shown in FIG. 6 to momentarily ignore position feedback from the IPT windings when the IPT signal is disrupted. As seen from the equations below, the sum of the squares of V a , V b , and V c is constant and each is proportional to a secondary voltage V s (Note V a , V b , and V c are shifted by 2π/3 with respect to one another):
[0000]
V
a
=
V
s
cos
θ
(
1
)
V
b
=
V
s
cos
(
θ
+
α
)
(
2
)
V
c
=
V
s
cos
(
θ
-
α
)
(
3
)
α
=
2
π
3
(
4
)
V
a
2
+
V
b
2
+
V
c
2
=
V
s
2
[
cos
2
θ
+
cos
2
(
θ
+
α
)
+
cos
2
(
θ
-
α
)
]
V
a
2
+
V
b
2
+
V
c
2
=
V
s
2
[
cos
2
θ
+
(
cos
θcosα
-
sin
θsinα
)
2
+
(
cos
θcosα
+
sin
θsinα
)
2
]
(
5
)
cos
α
=
-
1
2
(
6
)
sin
α
=
3
2
(
7
)
V
a
2
+
V
b
2
+
V
c
2
=
V
s
2
[
cos
2
θ
+
(
-
cos
θ
2
-
3
2
sin
θ
)
2
+
(
-
cos
θ
2
+
3
2
sin
θ
)
2
]
(
8
)
V
a
2
+
V
b
2
+
V
c
2
=
[
cos
2
θ
+
cos
2
θ
4
+
3
2
cos
θ
sin
θ
+
3
sin
2
θ
4
+
cos
2
θ
4
-
3
2
cos
θ
sin
θ
+
3
sin
2
θ
4
]
(
9
)
V
a
2
+
V
b
2
+
V
c
2
=
V
s
2
[
cos
2
θ
+
cos
2
θ
2
+
3
2
cos
3
sin
2
θ
4
+
cos
2
θ
4
-
3
2
cos
θ
sin
θ
+
3
sin
2
θ
4
]
(
10
)
V
a
2
+
V
b
2
+
V
c
2
=
V
s
2
[
cos
2
θ
+
cos
2
θ
2
+
3
sin
2
θ
2
]
=
3
2
V
s
2
[
cos
2
θ
+
sin
2
θ
]
=
3
2
V
s
2
(
11
)
V
a
2
+
V
b
2
+
V
c
2
=
3
2
V
s
2
(
12
)
[0051] The phase of the secondary relative to the primary may be derived by the algorithm shown in FIG. 5 . Since the secondary voltages V a , V b , and V c are AC signals, the normal polyphase relationship between voltages in a three-phase winding are modulated by the inductive power transfer (IPT) source frequency. In the absence of such modulation, the phase of the secondary relative to the primary may be determined by taking the 4-quadrant arctangent 40 of a “cosine” 37 and “sine” 38 signal. The three secondary voltages V a , V b , and V c may be filtered in a narrow-band bandpass filter 39 to isolate the fundamental frequency and reject non-synchronous noise. The three secondary voltages pass through an absolute value circuit 36 in order to make a voltage with a non-zero average amplitude that is proportional to the phase-modulated AC signal amplitude. The cosine of the secondary voltages is formed in block 37 and the sine in block 38 . However, the resulting phase measurement would be corrupted with each cycle of the AC frequency as the secondary voltages pass through zero volts. Low pass filter 75 filters out the high-frequency modulation of the signal to reveal the low-frequency phase information. The phase 41 is recovered by taking the four-quadrant arc-tangent 40 of the filtered sine 38 and cosine 37 signals. The result is a signal, Measured Theta 41 (Meas. Theta (θ)), that varies from −π it to π at twice the frequency (one half the spatial period) of the IPT winding period λ IPT as shown in FIG. 2 . Since λ IPT was selected to be substantially equal to twice the linear synchronous motor (LSM) wavelength (λ LSM ), the resulting Measured Theta 41 signal is directly related to the phase of the LSM.
[0052] However, the Measured Theta 41 signal may invariably contain some phase distortion relative to the true phase of the LSM. The distortion is caused by imperfections in the physical location of the windings (geometrical errors), errors due to stray flux leakage from the LSM windings to the IPT secondary and distortions caused by the absolute value circuit 36 applied to the signal during the phase recovery processing 29 . The absolute value circuit 36 alone produces a distortion at the 3rd harmonic of the fundamental period. If not corrected, these distortions may lead to vibrations in the LSM when used to commutate the motor and a loss in motor efficiency. The following equations show the phase angle recovery as demonstrated in FIG. 5 from the three phase voltages V a , V b , and V c :
[0000]
V
c
-
V
b
=
V
s
[
cos
(
θ
-
α
)
-
cos
(
θ
+
α
)
]
(
13
)
V
c
-
V
b
=
V
s
[
cos
θ
cos
α
+
sin
θ
sin
α
-
cos
θ
cos
α
+
sin
θ
sin
α
]
(
14
)
V
c
-
V
b
=
V
s
2
sin
θ
sin
α
(
15
)
V
c
-
V
b
=
3
V
s
sin
θ
(
16
)
sin
θ
=
V
c
-
V
b
3
V
s
(
17
)
2
V
a
-
V
b
-
V
c
=
V
s
[
2
cos
θ
-
cos
(
θ
+
α
)
-
cos
(
θ
-
α
)
]
(
18
)
2
V
a
-
V
b
-
V
c
=
V
s
[
2
cos
θ
-
cos
θ
cos
α
+
sin
θ
sin
α
-
cos
0
cos
α
+
sin
θ
sin
α
]
(
19
)
2
V
a
-
V
b
-
V
c
=
V
s
[
2
cos
θ
-
2
cos
θ
(
-
1
2
)
]
(
20
)
2
V
a
-
V
b
-
V
c
=
3
V
s
cos
θ
(
21
)
cos
θ
=
2
V
a
-
V
b
-
V
c
3
V
s
(
22
)
θ
=
tan
-
1
(
sin
θ
cos
θ
)
=
tan
-
1
(
sin
θ
1
cos
θ
)
(
23
)
θ
=
tan
-
1
(
(
V
c
-
V
b
3
V
s
)
(
3
V
s
2
V
a
-
V
b
-
V
c
)
)
=
tan
-
1
(
3
(
V
c
-
V
b
)
2
V
a
-
V
b
-
V
c
)
(
24
)
[0053] FIG. 6 is a block diagram of the 3 rd order state estimator 44 that may be used to combine inertial measurements with phase measurements in order to derive estimates of vehicle position 59 , velocity 56 and motor phase 54 angle. The position sensor may be improved by incorporating an inertial sensor with the phase measurement 41 calculated in FIG. 5 to derive an improved “estimate” of motor phase: Estimated Theta 54 (Est. Theta). A 3rd order state estimator 44 as shown in FIG. 6 , may be used to optimally combine acceleration data 55 from an inertial sensor 14 with the position data (Measured Theta 41 ) recovered from the inductive power transfer (IPT) windings. In one embodiment, the acceleration data 55 is based on or derived from the x-axis component of the acceleration measurement provided by the inertial sensor 14 . The 3rd order state estimator 44 is a dynamic system, implemented in a microprocessor or digital signal processor that produces “estimates” of position 59 , velocity 56 and accelerometer bias 65 . The resulting signals may be used in a feedback control law to perform closed loop control of the vehicle position. The state estimator 44 may produce a signal that is substantially free of distortions that may be used for motor commutation in addition to position 59 and velocity 56 signals that indicate the current state of the vehicle/train.
[0054] The signal from the inertial sensor 55 may be integrated once to produce a velocity signal (Estimated (Est.) Velocity 56 ) and a second time to produce a position signal (Estimated Position (Est. Pos.) 59 ). However, any bias on the inertial signal 55 would lead to an ever-increasing error that would rapidly degrade the utility of the state estimates. The state estimator 44 corrects for this error by comparing the state estimate of position 59 with the position measurement derived from the IPT windings and applying feedback in such a way that the inertially-derived position is driven to converge to the IPT-derived position measurement. Feedback gains L 1 47 , L 2 48 and L 3 49 may be used to set the dynamic response of the state estimator 44 and thereby establish a frequency below which the position recovered from the IPT windings 41 dominates the response and above which the twice-integrated inertial sensor position 59 dominates the response.
[0055] The inertial measurement 55 may be scaled in gain block 42 to appropriate units. The acceleration signal is integrated to produce a velocity estimate 56 in integrator 45 . The velocity signal is integrated again in integrator 43 to produce the Estimated Position signal 59 . The initial condition on the position integrator 43 is selected from switch 61 to come from either of three sources: a GPS-derived initial position 62 , an initial position derived from an RFID tag 63 or possibly from an initial position set manually by the vehicle operator 64 . Note that the initial position may be only applied when the state estimator 44 is first turned on. Once started, the state estimator 44 may rapidly force the Estimated Position 59 signal to conform to the phase measurement signal 41 .
[0056] The Estimated Position signal 59 may have linear units such as meters that are useful for performing closed loop speed or position control of the vehicle/train. The Estimated Position signal 59 may be converted into units of motor phase in order to compare with the Measured Theta signal 41 derived from the IPT windings. Gain block 58 converts the linear position units of Estimated Position signal 59 to equivalent motor phase angle in radians. The phase signal is converted to the range of −π to π by taking the modulo(2π) in block 57 of the phase signal. The resulting Estimated Theta 54 is compared with the Measured Theta 41 signal from the IPT detection circuit in summer 47 and the resulting error, when scaled to appropriate linear units in gain block 60 , is used to drive the Estimated Position 59 signal into convergence.
[0057] In normal operation switch 53 may connect the estimator error signal 76 to the feedback gains L 1 47 , L 2 48 and L 3 49 . However, during instants when the IPT signal is not available, the V IPT — OK signal 35 may momentarily hold the state estimator error signal 76 at 0 and therefore not allow erroneous Measured Theta 41 measurements to corrupt the state estimates of position 59 and velocity 56 .
[0058] Feedback gains L 1 -L 3 ( 47 - 49 ) force the state estimates to converge to values that are consistent with the phase measurements 41 derived from the IPT windings. Feedback gain L 3 may be applied to the state estimator error 76 and integrated in bias integrator 50 and summed with the acceleration measurement 55 in summer 51 . An initial estimate of acceleration bias in block 65 may be used to reduce the time it takes the state estimator 44 to converge to the correct bias when first turned on. Over time, however, the inertial sensor bias 65 may drift. Bias integrator 50 may track the bias 65 in order to maintain convergence between the Estimated Theta 54 and Measured Theta 41 signals. The bias integrator 50 integrates the state estimator error signal 76 and therefore may only converge to a stable estimate of accelerometer bias 65 when the state estimator error 76 is zero mean. This ensures that the difference between Estimated Theta 54 and Measured Theta 41 is zero mean.
[0059] The feedback gains L 1 47 , L 2 48 and L 3 49 may be selected to achieve a desired dynamic response in the state estimator 44 . The dynamic response may be determined by considering the types of errors that are present on the two sensors that are available: the inertial sensor and the position signal derived from the IPT windings. The IPT windings produce a reliable estimate of motor phase, but may also contain error sources at higher frequencies. The inertial sensor 14 (see FIG. 1 ), when twice integrated, produces an extremely accurate indication of position, but is prone to drift at low frequencies. The state estimator 44 combines the two signals to extract the best information from both: low frequency data from the IPT windings corrects for drift of the inertial sensor while the inertial sensor provides a position signal that is free from harmonic errors.
[0060] The state estimator may also be simplified using Laplace Transforms, in which case the integrator blocks 50 , 45 , and 43 may be represented as 1/s (“s” is the result of applying the Laplace Transform to convert a differential equation to an algebraic equation). In this simplification, the state controller may be represented as the following relationship between the gains L 1 -L 3 ( 47 - 49 ) and the response of estimated position 59 to each of the two inputs that drive the response: Measured Theta and Acceleration.
[0000]
y
Acceleration
=
s
s
3
+
L
1
s
2
+
L
2
s
+
L
3
(
25
)
y
MeasuredTheta
=
L
1
s
2
+
L
2
s
+
L
3
s
3
+
L
1
s
2
+
L
2
s
+
L
3
(
26
)
[0061] The two transfer functions can be plotted as a Bode diagram with consistent units if Inertial Position is used instead of Acceleration. Inertial Position is the second integral of Acceleration, or equivalently, Acceleration can be considered as the 2nd derivative of Inertial Position.
[0000]
InertialPosition
=
1
s
2
Acceleration
(
27
)
[0062] The transfer function of estimate position (y) to Inertial Position is therefore:
[0000]
y
Inertial
Position
=
y
Acceleration
s
2
=
s
3
s
3
+
L
1
s
2
+
L
2
s
+
L
3
(
28
)
[0063] The two transfer functions (Estimated Position/Measured Theta and Estimated Position/Inertial Position) are shown in a Bode diagram as FIG. 10 . The Bode diagram shows the role of Measured Theta driving the response at low frequency and the inertial signal driving response at high frequency. The state estimator bandwidth determines the transition frequency. For example, thee gain blocks 47 - 49 may be set to achieve a desired bandwidth in order to achieve a well-damped response. For example, L 1 =3.75 ω n , L 2 =3 ω n 2 , and L 3 =ω n 3 wherein ω=2πf and f=frequency (Bandwidth).
[0064] One may initially seek to use the accelerometer signal alone and dispense with the IPT-derived position signal. The accelerometer drift would become significant if it were not for the feedback provided by the state estimator 44 that forces the convergence between the twice-integrated accelerometer signal shown by estimated position 59 with the IPT-derived position signal 41 . Once the state estimator 44 corrects the drift of the accelerometer, the accelerometer may be used to provide a signal of remarkably high resolution. The resolution limit is constrained by the electrical noise of the accelerometer and the bandwidth of the state estimator 44 . For example, a typical low cost accelerometer might exhibit wide-band noise in the range of 100 □G/root-Hertz or about 0.001 M/sec2/root-Hertz. When integrated in a state estimator with a bandwidth of 1 Hertz, the resulting position signal may have an error due to accelerometer noise of roughly 15 microns (1-sigma). At higher frequencies, the error from the accelerometer becomes even smaller. Since the function of the position signal is to commutate the linear synchronous motor (LSM) and provide position information about the vehicle, precision significantly less than about 1% of the motor wavelength is not significant. For typical motor wavelengths in the range of 0.2 meter to 1 meter, a practical limit to useable resolution is approximately 2 to 10 millimeter. This translates into a 1-sigma specification of approximately 300 to 1500 microns. Lowering the state estimator bandwidth so as to use the (error-free) accelerometer at even lower frequencies may increase the position error due to accelerometer noise. At an estimator bandwidth of 0.133 Hz, the accelerometer noise would equal 300 microns (1-sigma). A bandwidth of 0.133 Hz corresponds to a temporal period of 7.5 seconds. In other words, the accelerometer signal may be used to provide position information sufficient for motor commutation when the drift is corrected by comparing with some other position sensor at no more than once every 7.5 seconds. At a vehicle speed of 25 meters/sec (approximately 55 MPH), the vehicle travels 187 meters in 7.5 seconds.
[0065] The output of the state estimator 44 may be transmitted to the wayside controller shown in FIG. 1 , where it may be used to commutate the LSM windings, using a radio link. There are a number of commercially available radio communication protocols that may be considered for this application. The radio link may exhibit low and deterministic latency. Latency is the time between when the position signal is available to be transmitted and when the wayside controller receives it. For typical radio communication protocols, the actual bit transmission rate is often more than adequate. The latency usually occurs due to protocol overhead in the transmitter or receiver. There exist other requirements for vehicle/train-to-track bi-directional communication to handle voice, vehicle/train status and safety-related information. Since this data does not have the same stringent latency requirements as the position information used for motor commutation, the position signal may be sent using a dedicated radio link as shown in FIG. 1 with a protocol optimized for low and deterministic latency while a separate radio link is used for all other vehicle/train communication.
[0066] The position signal provided by the state estimator 44 may be used to determine the relative position (phase) between the armature and stator of the LSM sufficient for the purpose of motor commutation. However, it does not indicate where the vehicle is along the track. The problem is that the state estimator output is simultaneously very accurate and very “uncertain”. The uncertainty is due to the fact that the LSM windings are periodic and there is nothing to identify which motor period the vehicle is aligned with. GPS and RFID data as shown in FIG. 1 may be used to provide additional information on vehicle location.
[0067] FIG. 7 is a block diagram of the radio link 15 used to transfer data from the on-board controller 13 to the wayside controller 11 . The wayside controller 11 may be used to commutate the LSM inverter 6 , control vehicle position and velocity by block 69 and manage on-board battery voltage. The state of the vehicle, Estimated Position, Estimated Velocity and Estimated Theta as shown in FIG. 6 as well as the state of charge of the battery, V bat , as shown in FIG. 4 are formed into a data packet 67 and sent to the wayside controller 11 using a dedicated radio link 15 and 12 . The wayside controller 11 compares the V bat signal with a desired reference voltage for the battery and alters the amplitude of the inductive power transfer (IPT) inverter 5 and the resulting voltage amplitude on the IPT primary windings 1 .
[0068] The wayside controller 11 implements a position control loop 69 to control the thrust of the linear synchronous motor (LSM). The output of the position control loop 69 is a signal 70 that may be used to drive the current command to the LSM inverter 6 . Along with the current command 70 , the wayside controller 11 may supply a phase angle 71 based on the Estimated Theta signal received from the on-board controller 13 via the radio transmitter 15 and receiver 12 .
[0069] There may be some latency between the measurement of Estimated Theta produced by the state estimator as shown in FIG. 6 in the on-board controller 11 and the application of the phase signal 71 to the LSM inverter 6 . As the latency becomes large relative to the frequency of the LSM inverter 6 (which is set by the vehicle speed divided by the motor pitch λLSM), an error in motor commutation may be introduced that may degrade motor performance and lead to a periodic ripple in thrust. At certain frequencies, corresponding to certain vehicle speeds, the ripple thrust may produce uncomfortable vibrations in the vehicle. If the latency of the Estimated Theta signal is constant and known, then the wayside controller 11 may adjust the Estimated Theta to account for the time delay. Therefore, it may be desirable to implement a radio link 15 with low and deterministic latency. At a vehicle speed of 50 M/sec (109 MPH) and a motor wavelength of 0.5 M, the LSM inverter frequency may be 100 Hertz (period of 0.01 seconds). To maintain a commutation error of 1% or less, the uncertainty in latency would need to be less than 1% of 0.01 seconds or less than 100 microseconds. Note that the actual latency may be larger than this limit, but the variance in the latency must be kept small and hence deterministic. Dedicating a radio link 15 to the task, and thereby avoiding conflicts with traffic on the communications link that does not require such deterministic performance, may permit this performance to be achieved.
[0070] In order to perform position control of the vehicle, the absolute position (or “global” position) of the vehicle must be known. The measurement derived from the IPT windings and inertial sensor gives a very precise measure of position within one period of the LSM. However, since the LSM winding is a repetitive pattern, it alone cannot indicate where along the track the vehicle is located. A Global Positioning System (GPS) receiver as shown in FIG. 1 may be used to give an approximate location of the vehicle. The error from the GPS is approximately 5 meters. The state estimator may force the GPS initialized error to converge to a precise phase of the LSM winding, but there may be an error of an integer number of windings due to the uncertainty in the initial GPS signal. For many vehicle/train operations, this error may be insignificant. However, for stopping at a vehicle/train platform to allow passengers to get on and off, an error of 5 meters may be intolerable. Also, if the vehicle is to be used in an automated freight terminal then more accurate knowledge of position may be required.
[0071] FIG. 8 is a simplified plan view of a track with LSM 8 and IPT windings 1 and RFID tags 72 spaced intermittently along the rail 9 . Radio Frequency Identification Tags 72 (RFID) may be used to improve the position estimate of the vehicle/train. RF tags may be located at discrete locations along the rail 9 . Each tag 72 may contain a unique ID code and the precise location of each tag 72 may be recorded in a database that is available to the on-board controller as shown in FIG. 1 . As the vehicle passes over the tag 72 , a reader 74 located on the vehicle as shown in FIG. 1 may read the tag 72 and compare the recorded position for the tag with the Estimated Position signal 59 shown in FIG. 6 . The difference may be used to determine an integer number of LSM periods (λ LSM ) as shown in FIG. 2 that may be applied to the Estimated Position signal 59 in order to determine the true position of the vehicle. Note that because the state estimator shown in FIG. 6 ensures that Estimated Position is synchronized to the LSM windings 8 , the only possible error in Estimated Position may be an integral number of motor pitches. The RFID tag position may be used to resolve the uncertainty. The tag 72 locations along the rail 9 may be located at a fixed relationship to the LSM winding 8 . Therefore the tag 72 locations stored in the database, when converted to motor phase, modulo(2π), may be a constant. Tag 72 locations may be placed at random locations with respect to LSM windings 8 as long as the tag 72 locations recorded in the database accurately reflect the true position of the tags. The tag 72 position only needs to be sufficiently accurate to resolve the vehicle position to the nearest wavelength of the LSM. An error of ¼ of a wavelength is sufficient to unambiguously resolve the vehicle position. Once a correction for the integer number of wavelengths is made, the Estimated Position signal may be accurate to the precision of the Measured Theta signal as shown in FIG. 5 derived from the IPT windings.
[0072] The RFID tags 72 may provide a redundant indication of vehicle position. As each tag 72 is crossed, the tag location may be extracted from the on-board database of tag locations and compared with the Estimated Position signal derived from the IPT windings. Once the initial uncertainty in position is resolved, subsequent RFID tags 72 should agree with the Estimated Position signal to within a small tolerance. If a position difference larger than a pre-determined threshold is detected, the vehicle may be brought to a stop and the discrepancy diagnosed.
[0073] In certain locations a GPS signal as shown in FIG. 1 may not be available with which to establish the initial position of the vehicle. If an RFID tag 72 is within range of the tag reader, then the initial position may be established using the tag location. In the event a tag is not near the vehicle, the initial position may be set by manually entering the known position in the state estimator as shown in FIG. 6 . Once the rough position of the vehicle is known and communicated to the wayside controller, the wayside controller may energize the IPT windings beneath the vehicle. Once the IPT signal is received, the phase relationship of the vehicle to the track may be established which may allow the motor to be commutated correctly. After the vehicle starts moving, it may cross over an RFID tag 72 , which may allow any remaining ambiguity in vehicle position to be resolved.
[0074] FIG. 9 is a graph showing exemplary errors associated with an inertial sensor such as an accelerometer revealing the merits of using an inertial sensor for position sensing. The figure is a logarithmic plot of acceleration versus frequency. Accelerometer error (actually the power spectral density of accelerometer noise) is plotted as a flat line at low frequency that falls off at higher frequency as the bandwidth of the inertial sensor is ultimately limited due to physical and electrical constraints. Many accelerometers exhibit errors that are relatively constant with frequency up to the bandwidth of the device. The second line on the plot shows the result of twice integrating the acceleration error signal. Integrating twice effectively divides the accelerometer error by the square of the frequency. This means that as long as the radian frequency (2π*frequency) is greater than 1, then the resulting position error may be numerically less than the acceleration error. At radian frequencies less than 1, the error in position may be numerically larger than the accelerometer error. A radian frequency of 1 corresponds to a frequency of ½π or 0.16 Hertz.
[0075] The total error that is produced by double integration of an accelerometer is found by integrating the noise density plot over a range of frequencies. The shaded area of FIG. 9 indicates the region over which the position error density signal is integrated in order to come up with a single number indicative of the overall root mean square (RMS) error due to the inertial sensor. The error derived by double integration becomes infinite at 0 frequency where one may establish a minimum frequency above which the position signal may be used. The bandwidth of the state estimator as shown in FIG. 6 , determined by gains L 1 -L 3 , sets the effective lower frequency above which the position estimate is determined by double integration of the acceleration signal. The upper limit of frequency has only a minor influence on the overall position error due to the rapid decrease in position error with frequency.
[0076] As an example, an accelerometer noise density of 0.001 meters/second 2 /square_root(Hz), when twice integrated over the range in frequency from 1 Hertz to 100 Hertz, produces an RMS error in position of approximately 15 microns (less than 0.001 inches). Therefore, an accelerometer may be used to produce a very high-quality position signal as long as a means exists to remove the drift caused by bias. The state estimator provides the means to correct for accelerometer bias drift by forcing convergence between Estimated Theta and Measured Theta at low frequency. At frequencies above the state estimator bandwidth, the double integration of acceleration dominates the response. The limited bandwidth of the state estimator does not permit the high frequency errors of the IPT-derived phase measurement to corrupt the Estimated Theta signal that is sent to the wayside controller and used to commutate the linear synchronous motor (LSM).
[0077] FIG. 10 is a Bode diagram plot of the state estimator output (Estimated Position 59 as shown in FIG. 6 ) to the two sensors: Measured Theta 41 derived from the inductive power transfer (IPT) windings, and the inertial sensor 14 . The state estimator output follows the Measured Theta 41 input at low frequencies, but the response falls off rapidly at frequencies above the bandwidth of the state estimator. At frequencies above the state estimator bandwidth, the state estimator output is dominated by the accelerometer measurement.
[0078] The “Accelerometer” response in FIG. 10 is the response to “inertial position” which is the double integration of acceleration. Since Measured Theta 41 and Acceleration have different units (position versus acceleration), it is difficult to visualize the effect of the state estimator bandwidth on the response. However, by plotting the response to inertial position rather than acceleration, the transfer functions have comparable units and can be plotted on the same axes.
[0079] The vertical axis is the ratio of the response (estimated position) to the input: either Measured Theta or the 2nd integral of acceleration (Inertial Position). The horizontal axis is frequency (in Hertz). Both the horizontal and vertical axes are logarithmic in order to show the large change in magnitude of response over a large range in frequency. The vertical scale covers the range from 1/100 to 10 (10 −2 to 10 1 ). Unity response (output equal to input) is indicated by 10°=1. The horizontal axis covers a range in frequency from 1/100 Hz to 100 Hz (10 −2 to 10 2 ).
[0080] FIG. 11 is a flowchart of an exemplary process for determining a position of a moving vehicle. Block 1102 depicts the step of receiving at a plurality of receivers inductive power from an inductive power source. Block 1104 depicts the step of determining a position of the vehicle relative to a position of the inductive power source. This determination of position is based on position information derived from the inductive power received at the plurality of receivers and based on acceleration of the vehicle. Block 1106 depicts the step of estimating a vehicle position from at least one of a GPS receiver and an RFID reader, the RFID reader configured to read one or more markers located outside the vehicle. Block 1108 depicts the step of comparing the vehicle position estimate to the position determined from at least one of the inductive power received at the plurality of receivers and the acceleration of the vehicle. Block 1110 depicts the step of identifying a fault in measurement of the position of the vehicle based on the comparison of the vehicle position estimate to the position determined from at least one of the inductive power received at the plurality of receivers and the acceleration of the vehicle. Block 1112 depicts the step of updating the vehicle position based on the estimate of vehicle position. Block 1114 depicts the step of correcting an error in the information about the acceleration of the vehicle based the position determined of the vehicle. Other exemplary processes may omit or add one or more of steps 1102 - 1114 , or operate in a different order.
[0081] It is understood that one skilled in the art may recognize variations to the description of the invention based on this disclosure. For instance, the invention may provide a closed-loop inverter (incorporating position feedback to control motor commutation) that will permit a more efficient operation of the motor. The invention may also provide for on-board power for brakes, train-to-track communication and have energy available for future installation of operator comforts such as lights and air conditioning. The proposed scheme will combine, in a single set of auxiliary windings that lie adjacent to the main propulsion windings, a means of inductively coupling power to the vehicle while simultaneously deriving a position signal that can be used to commutate the linear motor. The position-sensing scheme will make use of an on-board inertial sensor that, when combined with information derived from the IPT windings will provide a position signal that is extremely accurate and exhibits high tolerance to various forms of errors that can limit the accuracy of traditional inductive position sensing schemes. The position-sensing method, unlike other inertial position sensing methods, is accurate even at standstill and therefore can be used as a control signal for closed loop position control of the vehicle. Position control of the vehicle may allow for increased throughput in load and unload operations in a freight terminal compared to traditional, speed-control methods. In one embodiment, it may be desirable to adapt a commercial radio link to use to communicate position data to the wayside inverters. While it is possible to use the IPT windings, or similar windings, to provide bi-directional train-to-track communication, it may be desirable to use commercially available radio technology to perform this communication. The proposed position-sensing scheme has a requirement for low-latency and highly deterministic communication from the train to the LSM inverters. In one embodiment, it may be practical to implement a custom protocol on a commercially available radio frequency specifically for communicating position information to the inverter cabinet for the purpose of motor commutation. This link would be in parallel with any existing train-to-track communication scheme used for normal train status and control.
[0082] Appendix A is attached to provide a comprehensive list of components or items mentioned in the accompanying drawings.
APPENDIX A
Item Description
[0000]
1 Wayside IPT winding
2 On-board IPT Secondary
3 Secondary core
4 a Secondary winding, Phase a
4 b Secondary winding, Phase b
4 c Secondary winding, Phase c
5 IPT Inverter, Primary
6 LSM Inverter
7 LSM Block switch
8 LSM Winding
9 Rail
10 Vehicle
11 Wayside controller
12 Wayside radio link
13 On-board controller
14 Inertial sensor
15 On-board radio link
16 Magnet array
17 Grid power
18 IPT Block switch
19 LSM Wavelength
20 IPT Wavelength
21 Primary Tuning Capacitor
22 a Secondary Tuning capacitor, phase a
22 b Secondary Tuning capacitor, phase b
22 c Secondary Tuning capacitor, phase c
23 Rectifier, On-board
24 DC Link Capacitors
25 Battery
26 Inverter, on-board
27 “hotel” power, on-board
28 a Secondary voltage, phase a
28 b Secondary voltage, phase b
28 c Secondary voltage, phase c
29 Voltage monitor circuit
30 Square function
31 summation block
32 low pass filter
33 Minimum V-squared
34 Comparator
35 Voltage OK signal
36 Absolute value function
37 “Cosine” Phase
38 “Sine” Phase
39 Narrow-band bandpass filter
40 4 quadrant arc-tangent
41 Phase measurement
42 Accelerometer scale factor
43 Estimated (Est.) Theta Integrator
44 State Estimator
45 Estimated (Est.) Velocity integrator
46 Summer, observer error
47 Feedback gain, L 1
48 Feedback gain, L 2
49 Feedback gain, L 3
50 Acceleration bias integrator
51 Summer, acceleration
52 Summer, Velocity
53 Switch, Observer error
54 Estimated (Est.) Phase signal
55 Acceleration measurement
56 Estimated (Est.) Velocity signal
57 Modulo 2π
58 Scale: Convert linear position to phase
59 Estimated Position (Est. Pos.) signal
60 Scale: convert phase to linear units
61 Initial position select
62 Initial position from GPS
63 Initial position from RFID tag
64 Initial position entered manually
65 Initial estimate of accelerometer bias
66 Battery voltage measurement
67 Data packet sent to wayside controller
68 Controller, Battery voltage
69 Controller, Vehicle position
70 Current command to LSM inverter
71 Phase angle to LSM inverter
72 RFID tag
73 GPS Unit
74 RFID Reader
75 low pass filter
76 State estimator error signal | Linear synchronous motors (LSM) propel rail vehicles with greater efficiency and less environmental impact than diesel locomotives. LSM engines may require a position signal to commutate the windings of the ISM. This disclosure describes systems and methods for accurate determination of vehicle position based on position information derived from inductive power received and acceleration of the vehicle. Another aspect of the systems/methods is to estimate vehicle position with GPS and/or RFID readings of tags external to the vehicle. These estimates may be used to identify faults in vehicle position measurement, update the determined vehicle position, and correct acceleration estimates. | 1 |
[0001] The present invention relates to a vulcanizable composition containing a specific hydrogenated nitrile rubber, a cross-linking agent and carbon nanotubes, a process for preparing such compositions, the vulcanization and use thereof.
BACKGROUND OF THE INVENTION
[0002] Elastomers in principle have found widespread applications in numerous applications. Furtheron a lot of specialty rubbers are available with dispose of a broad range of mechanical, chemical as well as physical properties. Nitrile rubber (NBR) as well as the hydrogenation product thereof, i.e. hydrogenated nitrile rubber, also abbreviated as “HNBR”, represent such specialty rubbers. In particular HNBR has very good heat resistance, an excellent resistance to ozone and chemicals and also an excellent oil resistance. HNBR is used, for example, for seals, hoses, belts and clamping elements in the automobile sector, also for stators, oil well seals and valve seals in the field of oil extraction and also for numerous parts in the aircraft industry, the electronics industry, mechanical engineering and shipbuilding.
[0003] However, with the developing of technology, the demands of modern industries for functional rubbery accessories become stricter. It is essential to look for new vulcanizable compounds combining specialty rubbers with additives to improve the properties of elastomeric materials. Since the discovery of carbon nanotubes (CNTs), they have attracted many researchers' attentions owing to their excellent mechanical, electrical and thermal properties. CNTs as reinforcing fillers incorporated into elastomers can improve the mechanical properties of the matrix effectively.
[0004] Carbon nanotubes can be viewed as elongated fullerenes (Nature, 1985, Vol. 318, 162). Like fullerenes, carbon nanotubes are made of hexagons, with pentagons only on the ends. Structurally, the shape of a CNT could be imagined that a grapheme sheet rolls into tubule form with end seamless caps together with very high aspect ratios of 1000 or more. As individual molecules, the CNT is believed to be a defect-free structure leading a high strength despite their low density.
[0005] There are two basic forms for carbon nanotubes, those produced from a single graphite sheet, referred to as single wall nanotubes (SWNTs), and those nanotubes made up of several concentric sheets known as multi-wall nanotubes (MWNTs). SWNTs have created considerable interest in the academic community with several pertinent reviews on the subject including those by Bahr & Tour (J. Mater. Chem., 2002, 12, 1952), Hirsch (Angewandte Chemie-International Edition, 2002, 41, 1853), Colbert (Plastics Additives & Compounding, January/February 2003, 18) and Baughman & Heer (Science, 2002, 297, 787)
[0006] Since carbon nanotubes were discovered more than two decades ago, there have been a variety of techniques developed for producing them. Iijima (Nature, 1991, 354, 56) first observed multi-walled nanotubes. Iijima et al. and Bethune et al. (Nature, 1993, 363, 605) independently reported the synthesis of single-walled nanotubes a few years later. Primary synthesis methods for single and multi-walled carbon nanotubes include arc-discharge (Nature, 1997, 388, 756), laser ablation (Applied Physics A: Materials Science & Processing, 1998, 67, 29), gas-phase catalytic growth from carbon monoxide (Chemical Physics Letters, 1999, 313, 91), and chemical vapor deposition (CVD) from hydrocarbons (Applied Physics Letters, 1999, 75, 1086; Science, 1998, 282, 1105). Subsequent purification steps are required to separate the tubes. The gas-phase processes tend to produce nanotubes with fewer impurities and are more amenable to large-scale processing. Though there are no low-cost, large scale production methods to date, the traditional methods are being developed further and new methods such as fluidized bed reactors are being investigated to create a steady, reasonably priced CNT supply. The low CNT availability and their high prices have limited realization of polymer-CNT composites for many practical applications.
[0007] Hydrogenated carboxylated nitrile rubber (also abbreviated as “HXNBR”), prepared by the selective hydrogenation of carboxylated nitrile-conjugated diene rubber (also abbreviated as “XNBR”, being a co-polymer comprising repeating units of at least one conjugated diene, at least one unsaturated nitrile, at least one carboxylated monomer and optionally further comonomers), is a specialty rubber which has very good heat resistance, excellent ozone and chemical resistance, and excellent oil resistance. Coupled with the high level of mechanical properties of the rubber (in particular the high resistance to abrasion) it is not surprising that XNBR and HXNBR have found widespread use in the automotive (seals, hoses, bearing pads) oil (stators, well head seals, valve plates), electrical (cable sheeting), mechanical engineering (wheels, rollers) and shipbuilding (pipe seals, couplings) industries, amongst other industries.
[0008] The process for preparation of HXNBR polymers has been described in WO-A-2001/077185 while several other patents applications have been filed relating to various compounding techniques with respect to HXNBR polymers like e.g. WO-A-2005/080493and WO-A-2005/080492.
[0009] Carbon nanotubes, sometimes considered as the “ultimate” fibers, have different and interesting applications. One that has not yet been explored in detail is the question of incorporating the tubes into elastomer materials. Up to now solvent mixing, melt mixing and the spray drying process have been employed as processing methods to prepare some rubber/CNTs composites. The rubber matrixes in the existing studies include natural rubber (NR), styrene butadiene rubber (SBR), chloroprene rubber, silicone rubber, fluorocarbon elastomer (FKM) and hydrogenated acrylonitrile rubber (HNBR).
[0010] In Composites Science & Technology, 2003, 63, 1647 the impact of using carbon nanoparticles in silicone based elastomers on the mechanical properties of the resulting specimens is investigated. Using single-wall carbon nanotubes or larger carbon nanofibrils leads to an enhancement of the initial modulus of the resulting specimens as a function of the filler load, however, accompanied by a reduction of the ultimate properties.
[0011] The incorporation of carbon nanotubes into polymer matrices has already been explored for a variety of polymers such as siloxanes, isoprene rubber, nitrile butadiene, fluoro polymers (FKM), and hydrogenated nitrile butadiene rubber (HNBR).
[0012] In Journal of Material Science, 2006, 41, p. 2541 the effect of MWNTs on curing and mechanical properties of HNBR is described. Two methods are used to prepare the nanocomposites. In the first method CNTs were mixed into HNBR directly on a two roll mill with a curing agent at 50° C. for 10 min, and then the corresponding compound was vulcanized at 170° C. through hot pressing for T90. The second method comprised that low molecular liquid HNBR (LHNBR) was firstly dissolved in acetone, subsequently, the surface modified CNTs were added into the solution, and then the ultrasonic dispersion was used on the mixture. Removing the acetone from the mixture by vacuum drying, a compound with CNTs pre-dispersed in LHNBR was obtained. When using this solvent method the highest tensile strength of the HNBR/MWNT-composites was 18.6 MPa with 25 phr MWNT content.
[0013] CN 1554693 discloses the modification of HNBR via carbon nanotubes to enhance the heat-resistance, wearability and mechanical strength of HNBR. To prepare the HNBR composite rubber material carbon nanotubes and liquid rubber are ultrasonically mixed firstly and then added into partially hydrogenated nitrile-butadiene rubber to prepare a masterbatch; this masterbatch is then mixed with the remaining amount of hydrogenated nitrile-butadiene rubber, carbon black, zinc oxide and sulfurizing agent. The mixture is blended on a rolling mixer or a Banbury mixer; and then via vulcanization, the carbon nanotube modified hydrogenated nitrile-butadiene rubber is produced.
[0014] U.S. 2006/0061011 teaches the heat conductivity dependence of a polymer-carbon nanotube composite relating to the orientation of the carbon nanotubes. The recommended polymer matrices include styrene butadiene rubber (SBR), nitrile rubber (NBR) and hydrogenated nitrile rubber (HNBR). These polymer-carbon nanotube composites have been used for the manufacture of a pneumatic tire and a wheel for a vehicle.
[0015] CA 2,530,471 describes methods for the manufacturing of carbon nanotube-elastomer composites. It is further disclosed that the tensile modulus of such composites is enhanced. As elastomers polysiloxanes, polyisoprene, polybutadiene, polyisobutylene, halogenated polyisoprene, halogenated polybutadiene, halogenated polyisobutylene, low-temperature epoxy, EPDM, polyacrylonitrile, acrylonitrile-butadiene rubber, styrene butadiene rubber, EPM and other alpha-olefine based copolymers, as well as some particular fluorine containing copolymers are mentioned.
[0016] JP 2003/322216 teaches the manufacture of a toothed belt in which the surface of the tooth belt comprises a polymer latex, such as styrene butadiene rubber, chloroprene rubber, nitrite rubber and hydrogenated nitrile rubber. These polymer composites are generated through the mixing of carbon nanotubes in the presence of a resorcinol-formaldehyde resin.
[0017] In view of the steady demand for elastomeric compounds it is the object of the present invention to provide new vulcanizable compounds combining specialty rubbers with additives. Hydrogenated carboxylated acrylonitrile-butadiene rubber (“HXNBR”) itself already possesses an attractive property profile encompassing oil resistance, abrasion resistance as well as good adhesion to metals. However, due to the particular carboxyl group content HXNBR has not been investigated in such detail as other commodity elastomers and its behaviour in any compound is not foreseeable based on results which might be available for other more typical elastomers. As, however, the applications for which HXNBR may be suited, are extreme ones such as oil well specialties, high performance belts, and roll coverings there is still room for improvement and new HXNBR based compositions.
SUMMARY OF THE INVENTION
[0018] The present invention relates to a vulcanizable composition comprising a hydrogenated carboxylated nitrile rubber, at least one cross-linking agent, and carbon nanotubes, to a process for preparing such vulcanizable composition and to the vulcanization of such compositions as well as the use for preparing moulded articles.
DETAILED DESCRIPTION OF THE INVENTION
[0019] The vulcanizable composition according to the invention comprises a hydrogenated carboxylated nitrile rubber, at least one cross-linking agent, and carbon nanotubes.
[0020] As used throughout this specification, the term “hydrogenated carboxylated nitrile polymer” or HXNBR is meant to encompass a polymer having repeating units derived a) from at least one conjugated diene, b) at least one α,β-unsaturated nitrile, c) at least one monomer having at least one carboxylic group or a derivative thereof and d) optionally further one or more copolymerizable monomers, in which polymer more than 50% of the residual double bonds (RDB) present in the starting carboxylated nitrile polymer have been hydrogenated, preferably more than 90% of the RDB are hydrogenated, more preferably more than 95% of the RDB are hydrogenated and most preferably more than 99% of the RDB are hydrogenated.
[0021] The conjugated diene can be of any nature. Preference is given to using (C 4 -C 6 ) conjugated dienes. Particular preference is given to 1,3-butadiene, isoprene, 2,3-dimethylbutadiene, piperylene or mixtures thereof. Very particular preference is given to 1,3-butadiene and isoprene or mixtures thereof. Especial preference is given to 1,3-butadiene.
[0022] As α,β-unsaturated nitrile, it is possible to use any known 4-unsaturated nitrile, preferably a (C 3 -C 5 ) α,β-unsaturated nitrile such as acrylonitrile, methacrylonitrile, ethacrylonitrile or mixtures thereof. Particular preference is given to acrylonitrile.
[0023] As a monomer having at least one carboxylic group or a derivative thereof it is possible to use e.g. α,β-unsaturated monocarboxylic or dicarboxylic acids, their esters or amides.
[0024] As α,β-unsaturated monocarboxylic or dicarboxylic acids, preference is given to fumaric acid, maleic acid, acrylic acid and methacrylic acid.
[0025] As esters of α,β-unsaturated carboxylic acids, preference is given to using their alkyl esters and alkoxyalkyl esters. Particularly preferred alkyl esters of α,β-unsaturated carboxylic acids are methyl acrylate, ethyl acrylate, n-butyl acrylate, iso-butyl acrylate, tert.-butyl acrylate, n-butyl methacrylate, iso-butyl methacrylate, tert.-butyl methacrylate 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate and octyl acrylate. Particularly preferred alkoxyalkyl esters of α,β-unsaturated carboxylic acids are methoxyethyl (meth)acrylate, ethoxyethyl (meth)acrylate and methoxyethyl (meth)acrylate. It is also possible to use mixtures of alkyl esters, e.g. those mentioned above, with alkoxyalkyl esters, e.g. in the form of those mentioned above.
[0026] In a preferred embodiment a hydrogenated terpolymer based on acrylonitrile, butadiene and maleic acid is used. In a further preferred embodiment a hydrogenated terpolymer based on acrylonitrile, butadiene and an alkyl ester of an α,β-unsaturated carboxylic acid, in particular n-butyl acrylate, iso-butyl acrylate, and tert.-butyl acrylate is used.
[0027] Typically, the hydrogenated carboxylated nitrile polymer comprises in the range of from
a) 40 to 85 weight percent of repeating units derived from one or more conjugated dienes, preferably butadiene, b) 15 to 60 weight percent of repeating units derived from one or more -unsaturated nitriles, preferably acrylonitrile, and c) 0.1 to 30 weight percent of repeating units derived from one or more monomers having at least one carboxylic group or a derivative thereof, preferably from an α,β-unsaturated mono- or dicarboxylic acid and more preferably maleic acid, n-butyl acrylate, iso-butyl acrylate, or tert.-butyl acrylate,
wherein the three monomers a), b) and c) have to be chosen in the given ranges, so that they sum up to 100 weight percent.
[0031] Preferably, the hydrogenated carboxylated nitrile polymer comprises in the range of from
a) 55 to 75 weight percent of repeating units derived from one or more conjugated dienes, preferably butadiene, b) 25 to 40 weight percent of repeating units derived from one or more α,β-unsaturated nitriles, preferably acrylonitrile, and c) 1 to 7 weight percent of repeating units derived from one or more monomers having at least one carboxylic group or a derivative thereof, preferably from an α,β-unsaturated mono- or dicarboxylic acid and more preferably maleic acid, n-butyl acrylate, iso-butyl acrylate, or tert.-butyl acrylate,
wherein the three monomers a), b) and c) have to be chosen in the given ranges, so that they sum up to 100 weight percent.
[0035] More preferably, the hydrogenated carboxylated nitrite polymer comprises in the range of from
a) 55 to 75 weight percent of repeating units derived from one or more conjugated dienes, preferably butadiene, b) 25 to 40 weight percent of repeating units derived from one or more α,β-unsaturated nitriles, preferably acrylonitrile, and c) 1 to 30 weight percent of repeating units derived from one or more monomers having at least one carboxylic group or a derivative thereof, preferably from an α,β-unsaturated mono- or dicarboxylic acid and more preferably maleic acid, n-butyl acrylate, iso-butyl acrylate, or tert.-butyl acrylate,
wherein the three monomers a), b) and c) have to be chosen in the given ranges, so that they sum up to 100 weight percent.
[0039] In an alternative embodiment it is possible to use apart from the conjugated diene, the αβ-unsaturated nitrile, and the monomer having at least one carboxylic group or a derivative thereof one or more further copolymerizable monomers. Such copolymerizable monomers are known to those skilled in the art. Therefore the hydrogenated carboxylated nitrile polymer may further comprise repeating units derived from one or more copolymerizable monomers, such as alkylacrylate or styrene. Repeating units derived from such further copolymerizable monomers will replace either the α,β-unsaturated nitrile, or the conjugated diene portion of the nitrile rubber and it will be apparent to the skilled in the art that the above mentioned figures will have to be adjusted to result in 100 weight percent.
[0040] The preparation of hydrogenated carboxylated nitrile polymers by polymerization of the abovementioned monomers and a subsequent hydrogenation is adequately known to those skilled in the art and comprehensively described in the polymer literature. Typically such hydrogenated carboxylated nitrile polymers are prepared by radical emulsion polymerisation. Hydrogenated carboxylated nitrile polymers are also commercially available, e.g. as products from the product range of the trade names Therban® from Lanxess Deutschland GmbH.
[0041] The hydrogenated carboxylated nitrile polymers used for preparing the vulcanizable compositions according to the present invention typically have a Mooney viscosity (ML 1+4 at 100° C.) in the range from 5 to 90, preferably from 65 to85. This corresponds to a weight average molecular weight M w in the range 50 000-500 000, preferably in the range 200 000-450 000. The hydrogenated carboxylated nitrile rubbers used also have a polydispersity PDI=M w /M n , with M w being the weight average molecular weight and M n , being the number average molecular weight, in the range 1.7-6.0 and preferably in the range 2.0-3.0.
[0042] The determination of the Mooney viscosity (ML 1+4 at 100° C.) is carried out in accordance with ASTM standard D 1646.
[0043] Hydrogenated in this invention is preferably understood by more than 50% of the residual double bonds (RDB) present in the starting nitrile polymer/NBR being hydrogenated, preferably more than 90% of the RDB are hydrogenated, more preferably more than 95% of the RDB are hydrogenated and most preferably more than 99% of the RDB are hydrogenated.
[0044] The present invention is not restricted to a special process for preparing the hydrogenated carboxylated nitrile rubber. However, the HXNBR preferred in this invention is readily available as disclosed in WO-A-01/077185. For jurisdictions allowing for this procedure, WO-A-01/77185 is incorporated herein by reference.
[0045] The vulcanizable composition according to the invention comprises either single-wall carbon nanotubes (SWNTs) or multi-wall carbon nanotubes (MWNTs).
[0046] A SWNT is a molecular scale wire that has two key structural parameters. By folding a graphene sheet into a cylinder so that the beginning and end of a lattice vector in the graphene plane join together. The indices determine the diameter of the nanotube, and also the so-called ‘chirality’. Tubes are ‘arm-chair’ tubes, since the atoms around the circumference are in an arm-chair pattern. Nanotubes are termed ‘zigzag’ in view of the atomic configuration along the circumference. The other types of nanotubes are chiral, with the rows of hexagons spiraling along the nanotube axes (Surface Science, 2002, 500(1-3), p. 218).
[0047] Multi-walled nanotubes (MWNT) consist of multiple layers of graphite rolled in on themselves to form a tube shape.
[0048] Such carbon-nanotubes are either commercially available or may be prepared pursuant to processes known from prior art: Primary synthesis methods for single and multi-walled carbon nanotubes include arc discharge (Nature, 1991, 354, p. 56), laser ablation (Applied Physics A: Materials Science & Processing, 1998, 67(1), p. 29), gas-phase catalytic growth from carbon monoxide (Chemical Physics Letters, 1999, 313, p. 91), and chemical vapor deposition (CVD) from hydrocarbons (Applied Physics Letters, 1999, 75(8), p. 1086; Science, 1998, 282, p. 1105) methods. For application of carbon nanotubes in composites, large quantities of nanotubes are required, and the scale-up limitations of the arc discharge and laser ablation techniques would make the cost of nanotube based composites prohibitive. The gas-phase processes tends to produce nanotubes with fewer impurities and are more amenable to large-scale processing. It is a belief that gas phase techniques, such as CVD, for nanotube growth offer the greatest potential for the scaling-up of nanotube production for the processing of composites.
[0049] The composition according to the present invention typically comprise 1-50 parts by weight of carbon nanotubes, preferably 1-20 parts by weight, and more preferably 1-10 parts by weight of carbon nanotubes, in each case based on 100 parts by weight of hydrogenated carboxylated nitrile rubber.
[0050] The vulcanizable composition according to the present invention furthermore comprises one or more cross-linking agents. The invention is not limited to a special cross-linking agent. Peroxide based cross-linking agents as well as sulfur based cross-linking agents may be used alone or even in mixtures. Peroxide cross-linking agents or in-situ peroxide releasing cross-linking agents are preferred.
[0051] The invention is not limited to a special peroxide cross-linking agent. For example, inorganic or organic peroxides are suitable. Preferred are organic peroxides such as dialkylperoxides, ketalperoxides, aralkylperoxides, peroxide ethers, and peroxide esters, such as di-tert.-butylperoxide, bis-(tert.-butylperoxyisopropyl)-benzene, dicumylperoxide, 2,5-dimethyl-2,5-di(tert.-butylperoxy)-hexane, 2,5-dimethyl-2,5-di(tert.-butylperoxy)-hexene-(3), 1,1-bis-(tert.-butylperoxy)-3,3,5-trimethyl-cyclohexane, benzoyl-peroxide, tert.-butylcumylperoxide, tert.-butylperbenzoate and zinc peroxide. Such peroxides are readily commercially available.
[0052] Usually the amount of cross-linking agent and in particular of peroxide in the vulcanizable composition is in the range of from 1 to 10 phr (=per hundred parts of rubber, i.e. HXNBR), preferably in the range of from 4 to 8 phr. Peroxides might be applied advantageously in a polymer-bound form. Suitable systems are commercially available, such as Polydispersion T(VC) D-40 P from Rhein Chemie Rheinau GmbH, D (=polymerbound di-tert.-butylperoxy-isopropylbenzene).
[0053] In one embodiment the vulcanizable composition comprises
a) 100 parts by weight of HXNBR b) 1 to 10 parts by weight, preferably 4 to 8 parts by weight of at least one cross-linking agent, based on 100 parts by weight of HXNBR and c) 1 to 50 parts by weight, preferably 1 to 20 parts by weight, and more preferably 1 to 10 parts by weight of carbon nanotubes, based on 100 parts by weight of HXNBR.
Filler:
[0057] The inventive composition further optionally comprises at least one filler. The filler may be an active or an inactive filler or a mixture thereof.
[0058] The filler may be in particular:
highly dispersed silicas, prepared e.g. by the precipitation of silicate solutions or the flame hydrolysis of silicon halides, with specific surface areas of in the range of from 5 to 1000 m 2 /g, and with primary particle sizes of in the range of from 10 to 400 nm; the silicas can optionally also be present as mixed oxides with other metal oxides such as those of Al, Mg, Ca, Ba, Zn, Zr and Ti; synthetic silicates, such as aluminum silicate and alkaline earth metal silicate like magnesium silicate or calcium silicate, with BET specific surface areas in the range of from 20 to 400 m 2 /g and primary particle diameters in the range of from 10 to 400 nm; natural silicates, such as kaolin and other naturally occurring silica; glass fibers and glass fiber products (matting, extrudates) or glass microspheres; metal oxides, such as zinc oxide, calcium oxide, magnesium oxide and aluminum oxide; Magnesium oxide is preferred. metal carbonates, such as magnesium carbonate, calcium carbonate and zinc carbonate; metal hydroxides, e.g. aluminum hydroxide and magnesium hydroxide; carbon blacks; the carbon blacks to be used here are prepared by the lamp black, furnace black or gas black process and have preferably BET (DIN 66 131) specific surface areas in the range of from 20 to 200 m 2 /g, e.g. SAF, ISAF, HAF, FEF or GPF carbon blacks; rubber gels, especially those based on polybutadiene, butadiene/styrene copolymers, butadiene/acrylonitrile copolymers and polychloroprene;
or mixtures thereof.
[0068] Examples of preferred mineral fillers include silica, silicates, clay such as bentonite, gypsum, alumina, titanium dioxide, talc, mixtures of these, and the like. These mineral particles have hydroxyl groups on their surface, rendering them hydrophilic and oleophobic. This exacerbates the difficulty of achieving good interaction between the filler particles and the rubber. For many purposes, the preferred mineral is silica, especially silica made by carbon dioxide precipitation of sodium silicate. Dried amorphous silica particles suitable for use in accordance with the invention may have a mean agglomerate particle size in the range of from 1 to 100 microns, preferably between 10 and 50 microns and most preferably between 10 and 25 microns. It is preferred that less than 10 percent by volume of the agglomerate particles are below 5 microns or over 50 microns in size. A suitable amorphous dried silica moreover usually has a BET surface area, measured in accordance with DIN (Deutsche Industrie Norm) 66131, of in the range of from 50 and 450 square meters per gram and a DBP absorption, as measured in accordance with DIN 53601, of in the range of from 150 and 400 grams per 100 grams of silica, and a drying loss, as measured according to DIN ISO 787/11, of in the range of from 0 to 10 percent by weight. Suitable silica fillers are available under the trademarks HiSil® 210, HiSil® 233 and HiSil® 243 from PPG Industries Inc. Also suitable are Vulkasil® S and Vulkasil® N, from Lanxess Deutschland GmbH.
[0069] Often, use of carbon black as a filler is advantageous. Usually, carbon black is present in the polymer composite in an amount of in the range of from 20 to 200 parts by weight, preferably 30 to 150 parts by weight, more preferably 40 to 100 parts by weight. Further, it might be advantageous to use a combination of carbon black and mineral filler in the inventive polymer composite. In this combination the ratio of mineral fillers to carbon black is usually in the range of from 0.05 to 20, preferably 0.1 to 10.
Further Auxiliary Compounds
[0070] The polymer-carbon nanotube composition according to the invention can contain further auxiliary compounds for rubbers, such as reaction accelerators, vulcanizing accelerators, vulcanizing acceleration auxiliaries, antioxidants, foaming agents, anti-aging agents, heat stabilizers, light stabilizers, ozone stabilizers, processing aids, plasticizers, tackifiers, blowing agents, dyestuffs, pigments, waxes, extenders, organic acids, inhibitors, metal oxides, and activators such as triethanolamine, polyethylene glycol, hexanetriol, etc., which are known to the rubber industry.
[0071] These rubber aids may be used in conventional amounts, which depend inter alia on the intended use. Conventional amounts are e.g. from 0.1 to 50 wt.%, based on rubber. Preferably the composition comprises in the range of 0.1 to 20 phr of an organic fatty acid as an auxiliary product, preferably a unsaturated fatty acid having one, two or more carbon double bonds in the molecule which more preferably includes 10% by weight or more of a conjugated diene acid having at least one conjugated carbon-carbon double bond in its molecule. Preferably those fatty acids have in the range of from 8-22 carbon atoms, more preferably 12-18. Examples include stearic acid, palmitic acid and oleic acid and their calcium-, zinc-, magnesium-, potassium- and ammonium salts.
[0072] In a further embodiment the vulcanizable composition may comprise in the range of 5 to 50 phr of an acrylate as an auxiliary product. Suitable acrylates are known from EP-A1-0 319 320, in particular p. 3, 1. 16 to 35, from U.S. Pat. No. 5,208,294, in particular Col. 2, I. 25 to 40, and from U.S. 4,983,678, in particular Col. 2, 1. 45 to 62. Particular reference is made to zinc acrylate, zinc diacrylate or zinc dimethacrylate or a liquid acrylate, such as trimethylolpropanetrimethacrylate (TRIM), butanedioldimethacrylate (BDMA) and ethylenglycoldimethacrylate (EDMA). It might be advantageous to use a combination of different acrylates and/or metal salts thereof. Of particular advantage is often to use metal acrylates in combination with a Scorch-retarder such as sterically hindered phenols (e.g. methyl-substituted aminoalkylphenols, in particular 2,6-di-tert.-butyl-4-dimethylaminomethylphenol).
Preparation Of The Vulcanizable Composition According To The Present Invention:
[0073] A further object of the invention resides in the preparation of the vulcanizable compositions, wherein the HXNBR, the carbon-nanotubes and the cross-linking agent and optionally any of the other ingredients of the composition are mixed together.
[0074] Typically the mixing is performed at an elevated temperature that may range from 20° C. to 200° C.
[0075] The mixing may further be performed in the presence of a solvent which is then removed after mixing.
[0076] Normally the mixing time does not exceed one hour and a time in the range from 2 to 30 minutes is usually adequate.
[0077] The mixing is suitably carried out in an a blending apparatus, e.g. an internal mixer such as a Banbury mixer, or a Haake or Brabender miniature internal mixer. A two roll mill mixer also provides a good dispersion of the carbo-nanotubes as well as of the other optional additives within the elastomer. An extruder also provides good mixing, and permits shorter mixing times. It is possible to carry out the mixing in two or more stages, and the mixing can be done in different apparatus, for example one stage in an internal mixer and one stage in an extruder. However, it should be taken care that no unwanted pre-crosslinking (=scorch) occurs during the mixing stage.
[0078] The compounding and vulcanization may be performed as known to any artisan (see e.g. Encyclopedia of Polymer Science and Engineering, Vol. 4, p. 66 et seq. (Compounding) and Vol. 17, p. 666 et seq. (Vulcanization). Typically such vulcanization is performed at a temperature in the range of from 100 to 200° C., preferably 130 to 180° C. In one embodiment the preparation of a polymer vulcanizate comprises subjecting the inventive composition to a vulcanization during injection moulding.
[0079] A further object of the invention therefore is a vulcanizate obtained after vulcanization, preferably in the form of moulded articles such as a seal, a roll cover, a belt, a stator or a bearing pad for attachment to a track of a tracked vehicle.
[0080] These vulcanizates which may be obtained by vulcanizing the composition according to the present invention display enhanced tensile strength and modulus properties compared to HXNBR while maintaining elongation and strain at break properties.
EXAMPLES
[0081] The details of the raw materials used in the following Examples are summarized in the following Table 1.
[0000]
Raw materials
Type/Grades
available from
HXNBR
Therban ® XT 8999
Lanxess
Deutschland GmbH
Multi-walled carbon
Diameter
Chengdu Organic
nanotubes (MWNTs)
10~20 nm
Chemicals Co., Ltd
MgO
Chemical purity
Sinopharm Chemical
(>98.5%)
Reagent Co., Ltd
DCP (dicumylperoxide)
Chemical purity
Sinopharm Chemical
(>98.%)
Reagent Co., Ltd
Preparation Of Vulcanizable Compositions According To The Invention:
[0082] HXNBR and MWNTs were mixed using an internal mixer at the ratio of 9:1 by weight. The masterbatch with 10 wt % MWNTs was diluted into different concentrations of MWNT using a two-roll mill. The final concentration of the MWNTs in HXNBR were 0, 1, 2 and 4 part per hundred parts (phr) of HXNBR (see Table 2). The curing agent DCP was added after HXNBR/MWNTs masticating for 5 min. Finally, the HXNBR mixes were cured at 10° C. for 20 min.
Testing Procedures/Methods:
[0083] The tensile strength tests were carried out in an Instron 4465 tensile machine (Instron Co., UK) at a crosshead speed of 500 mm/min. The dumbbell shape samples were 75 mm in length, 1 mm in thickness, and 4 mm in width. Shore A hardness was measured by a hand-held Shore A durometer according to ASTM D2240-97. Results were read after 5 seconds. Dynamic mechanical analysis (DMA) was performed with DMA 242C (NETZSCH, Germany) under nitrogen at a heating rate of 5° C./min from −60° C.˜40° C. and a frequency of 1 Hz.
[0084] In the following Table 2 all amounts are given in parts per 100 parts by weight of HXNBR.
[0000]
TABLE 2
Sample
X1
(comparison)
X2
X3
X4
HXNBR
100
100
100
100
MWNTs
—
1
2
4
MgO
5
5
5
5
DCP
3
3
3
3
Hardness, Shore A
61
63
65
67
Tensile strength (MPa)
26.5
28.2
35.3
37.1
Elongation at break (%)
440
434
456
424
Modulus at 100% strain (MPa)
1.9
2.2
2.6
3.5
Modulus at 200% strain (MPa)
3.4
4.2
5.2
7.3
Modulus at 300% strain (MPa)
6.8
8.1
9.4
13.2
Permanent set (%)
5
5
8
8
[0085] As may be seen from Table 2 the addition of the MWNTs to HXNBR result in a significant reinforcement. The addition of MWNTs in particular resulted in considerable benefits to the physical properties and the magnitude of property enhancement could be related to the level of carbon nanotubes included in the composite recipe. The benefits to the polymer composite include, but are not restricted to an increase of the tensile strength, an increase, of the polymer composite modulus at 100, 200 and 300% strain and eventually an increase in hardness of the polymer composite. | The present invention provides a vulcanizable composition containing a specific hydrogenated nitrile rubber, at least one cross-linking agent and carbon nanotubes, a process for preparing such composition and the use thereof for preparing vulcanizates. Said vulcanizates exhibit excellent heat performance, oil resistance and mechanical strength. | 2 |
The present invention relates to α 2 -adrenoceptor agonists having analgesic activity. More particularly, the present invention relates to 4- (thien-3-yl)methyl!-imidazoles having improved analgesic activity.
BACKGROUND OF THE INVENTION
Clonidine is a centrally acting α 2 -adrenoceptor agonist with wide clinical utility as an antihypertensive agent. Clonidine is believed to act by inhibiting the release of norepinephrine from sympathetic nerve terminals via a negative feedback mechanism involving α 2 -adrenoceptors located on the presynaptic nerve terminal. This action is believed to occur in both the central (CNS) and peripheral (PNS) nervous systems. More recently, the role of α 2 -adrenoceptor agonists as analgesic agents in humans and antinociceptive agents in animals has been demonstrated. Clonidine and other α 2 -adrenoceptor agonists have been shown to produce analgesia through a non-opiate mechanism and, thus, without opiate liability. However, other behavioral and physiological effects were also produced, including sedation and cardiovascular effects. ##STR3##
Medetomidine and detomidine are α 2 -adrenoceptor agonists widely used clinically in veterinary medicine as sedatives/hypnotics for pre-anaesthesia. These compounds are hypotensive in animals and in humans, but the magnitude of this cardiovascular effect is relatively insignificant. ##STR4##
U.S. Pat. No. 3,574,844, Gardocki et al., teach 4- 4(or 5)-imidazolylmethyl!-oxazoles as effective analgesics. The disclosed compounds are of the general formula: ##STR5## Compounds of this type are insufficiently active and suffer from unwanted side effects.
U.S. Pat. No. 4,913,207, Nagel et al., teach arylthiazolylimidazoles as effective analgesics. The disclosed compounds are of the general formula: ##STR6## Compounds of this type are insufficiently active and suffer from unwanted side effects.
WO92/14453, Campbell et al., teach 4- (aryl or heteroaryl)methyl!imidazoles as effective analgesics. The disclosed compounds are of the general formula: ##STR7## The disclosed compounds are insufficiently active and suffer from unwanted side effects.
Kokai No. 1-242571, Kihara et al., disclose a method to produce imidazole derivatives for use, among other uses, as antihypertensive agents. ##STR8## A single mixture of compounds meeting the above formula was reportedly produced by the inventive method. This was a mixture of 4-(2-thienyl)-methylimidazole and 4-(3-thienyl)-methylimidazole represented by the following formula: ##STR9## The disclosed compounds are insufficiently active and suffer from unwanted side effects.
It is an object of the present invention to produce 4- (thien-3-yl)methyl!-imidazoles having improved analgesic activity.
It is another object of the present invention to produce 4- (thien-3-yl)methyl!-imidazole analgesics having reduced side effects.
SUMMARY OF THE INVENTION
Briefly, there is provided by the present invention compounds having improved analgesic activity of the formulae: ##STR10## wherein R is hydrogen or methyl, and
X is C 1-4 alkyl, bromine or chlorine; or ##STR11## wherein Y is hydrogen, C 1-4 alkyl, bromine or chlorine, and
Z is C 1-4 alkyl, bromine or chlorine.
DETAILED DESCRIPTION OF THE INVENTION
The compounds of the present invention may be made in basically a two step process. In the first step, an appropriately substituted precursor thiophene is obtained having hydrogen, C 1-4 alkyl, bromine or chlorine substituents as desired and in the required positions. This precursor thiophene will have an electrophilic carbon substituent at the 3-position. In the second step, a precursor imidazole having an anion at the 4-position capable of reacting with the electrophilic carbon of the precursor thiophene to leave a carbon bridge residue, is reacted with the precursor thiophene to produce the target skeleton followed by deoxygenation of the carbon bridge residue. Of course, many variations are possible. It may be desirable to substitute the thiophene initially, as described, or to modify the substitution on the thiophene following the formation of the base structure of the final compound. Also, in compounds where it is desirable to have methyl substitution on the carbon bridge residue, additional steps will be necessary.
Herein, a Grignard reaction is favored for use in the second step to join the thienyl moiety and the imidazolyl moiety. Thus, it is preferred that the precursor imidazole be substituted at the 4-position as a Grignard reagent and that the precursor thiophene is substituted at the 3-position with a carbonyl, such as, formyl or N,O-dimethylcarboxamido group.
The preferred precursor imidazole has the formula: ##STR12## where X 1 is iodo, bromo or chloro. This compound may be made by methods well known to the art, i.e., reaction between alkyl Grignard or magnesium and imidazolyl halide in dry, alcohol-free ether or THF or dichloromethane.
The preferred precursor thiophenes have the formula: ##STR13## where X, Y and Z are defined above. As starting materials to make the preferred precursor thiophenes AA, BB and CC, the preparation of various brominated and methylated thiophenes is well known from the literature.
Precursor thiophenes of type AA may be produced from 3-bromo-4-methylthiophene or 3-bromo-4-(bromo or chloro)thiophene by use of halogen metal exchange. In a first step, the compound is treated with an organo-alkali compound such as n-butyllithium, the product of which is reacted, in a second step, in situ with DMF. The reaction is quenched with aqueous ammonium chloride. The resultant compound is 4-methyl-thiophene-3-carboxaldehyde or 4-(bromo or chloro)-thiophene-3-carboxaldehyde. Precursor thiophenes of type BB, may be produced by much the same method as those of type AA with the use of different starting materials. The method just described to produce precursor thiophenes of type AA may be employed to produce those of type BB where the starting material is not 2-bromo or 5-bromo substituted. Thus, the halogen metal exchange may be employed with 2-(methyl or chloro)-3-bromo-4-(methyl or chloro or bromo) thiophene or 2-(methyl or chloro)-3-bromo-5-(methyl or chloro) thiophene to produce type BB precursor thiophenes which are 2-(methyl or chloro)-4-(methyl or chloro or bromo)-thiophene-3-carboxaldehyde or 2-(methyl or chloro)-5-(methyl or chloro)-thiophene-3-carboxaldehyde. Precursor thiophenes of type CC may be produced from 2-(methyl or chloro or bromo)-4-(methyl or chloro or bromo)-thiophene-3-carboxylate or 2-(methyl or chloro or bromo)-5-(methyl or chloro or bromo)-thiophene-3-carboxylate by two methods. In the first method, the carboxylate starting material is converted to the acid chloride and reacted with N,O-dimethylhydroxylamine to produce the Weinreb amide, thiophene type CC. In the second method, the carboxylate is reacted with N,O-dimethylhydroxylamine and an appropriate coupling agent, such as, DCC or CDI, to produce the Weinreb amide.
The precursor imidazole may be reacted with any of the precursor thiophenes of types AA or BB or CC by use of the Grignard Reaction. Where the precursor thiophene is of type AA or BB, a solution of the thiophene precursor is combined with a solution of the imidazole precursor at room temperature and the reaction is quenched with aqueous ammonium chloride solution to produce an imidazo thienyl methanol. The carbinol is deoxygenated to final product, where R is hydrogen, by use of a reducing agent, such as borane methyl sulfide in combination with TFA. Alternatively, the methanol is catalytically deoxygenated to final product, where R is hydrogen, by heating with Pearlman's catalyst and an equivalent of acid. To produce final product where R is methyl, the methanol is oxidized to the corresponding ketone with an oxidizing agent, such as MnO 2 or Jones Reagent and the resulting ketone is reacted with methyl Grignard to produce a carbinol which is deoxygenated as described immediately above. Where the precursor thiophene is of type CC, a solution of the thiophene precursor is combined with a solution of the imidazole precursor at room temperature and the reaction is quenched with aqueous ammonium chloride solution to produce an imidazo thienyl ketone. To produce final product, the ketone is reduced to the carbinol by use of a reducing agent, such as, sodium borohydride or lithium aluminum hydride and thereafter the carbinol is deoxygenated as described immediately above.
The protecting group on the precursor imidazole is exemplified herein as trityl, which is preferred. However, a person skilled in the art will readily recognize that other protecting groups are suitable. Suitable protecting groups include dimethylsulfamoyl or methoxymethyl. The trityl group is removed in the deoxygenation to final product or upon heating in a dilute acid and alcoholic solvent.
The most preferred compounds of the present invention are shown in Table I:
TABLE I______________________________________ ##STR14## Cp-1 ##STR15## Cp-2 ##STR16## Cp-3 ##STR17## Cp-4 ##STR18## Cp-5 ##STR19## Cp-6 ##STR20## Cp-7 ##STR21## Cp-8 ##STR22## Cp-9 ##STR23## Cp-10 ##STR24## ##STR25##______________________________________
The activity of compounds of the invention as analgesics may be demonstrated by the in vivo and in vitro assays as described below:
Alpha 2D adrenergic receptor binding assay
Male, Wistar rats (150-250 g, VAF, Charles River, Kingston, N.Y.) are sacrificed by cervical dislocation and their brains removed and placed immediately in ice cold HEPES buffered sucrose. The cortex is dissected out and homogenized in 20 volumes of HEPES sucrose in a Teflon®-glass homogenizer. The homogenate is centrifuged at 1000 g for 10 min, and the resulting supernatant centrifuged at 42,000 g for 10 min. The resulting pellet is resuspended in 30 volumes of 3 mM potassium phosphate buffer, pH 7.5, preincubated at 25° C. for 30 min and recentrifuged. The resulting pellet is resuspended as described above and used for the receptor binding assay. Incubation is performed in test tubes containing phosphate buffer, 2.5 mM MgCl 2 , aliquots of the synaptic membrane fraction, the ligand 3 H-paraaminoclonidine and test drug at 25°0 C. for 20 min. The incubation is terminated by filtration of the tube contents through glass fiber filter sheets. Following washing of the sheets with 10 mM HEPES buffer, the adhering radioactivity is quantified by liquid scintillation spectrometry.
Binding of the test drug to the receptor is determined by comparing the amount of radiolabeled ligand bound in control tubes without drug to the amount of radiolabeled ligand bound in the presence of the drug. Dose-response data are analyzed with LIGAND, a nonlinear curve fitting program designed specifically for the analysis of ligand binding data. This assay is described by Simmons, R. M. A., and Jones, D. J., Binding of 3 H-!prazosin and 3 H-!p-aminoclonidine to α-Adrenoceptors in Rat Spinal Cord, Brain Research 445:338-349, 1988.
Mouse Acetylcholine Bromide-Induced Abdominal Constriction Assay
The mouse acetylcholine bromide-induced abdominal constriction assay, as described by Collier et al. in Brit. J. Pharmacol. Chem. Ther., 32:295-310, 1968, with minor modifications was used to assess analgesic potency of the compounds herein. The test drugs or appropriate vehicle were administered orally (p.o.) and 30 minutes later the animal received an intraperitoneal (i.p.) injection of 5.5 mg/kg acetylcholine bromide (Matheson, Coleman and Bell, East Rutherford, N.J.). The mice were then placed in groups of three into glass bell jars and observed for a ten minute observation period for the occurrence of an abdominal constriction response (defined as a wave of constriction and elongation passing caudally along the abdominal wall, accompanied by a twisting of the trunk and followed by extension of the hind limbs). The percent inhibition of this response to a nociceptive stimulus (equated to % analgesia) was calculated as follows: The % Inhibition of response, i.e., % analgesia is equal to the difference between the number of control animals response and the number of drug-treated animals response times 100 divided by the number of control animals responding.
At least 15 animals were used for control and in each of the drug treated groups. At least three doses were used to determine each dose response curve and ED 50 (that dose which would produce 50% analgesia). The ED 50 values and their 95% fiducial limits were determined by a computer assisted probit analysis.
TABLE II______________________________________ Mouse Abdominal ConstrictionCompound Ki(nm) % Inhibition ED.sub.50______________________________________Cp-1 0.44 100% @30 mpkCp-2 0.47 0.4 mpkCp-3 0.39 0.4 mpkCp-4 0.97 100% @30 mpkCp-5 0.69 1.3 mpkCp-6 0.4 3.7 mpkCp-7 0.07 0.4 mpkCp-8 0.10 100% @30 mpkCp-9 0.29 100% @30 mpkCp-10 0.28 100% @30 mpk ##STR26## 6.1 100% @30 mpk ##STR27## 3.1 6.4 mpk ##STR28## 2.3 1.6 mpk ##STR29## 2.5 100% @30 mpk ##STR30## 33.5 7.8 mpk ##STR31## 11.4 67% @30 mpk ##STR32## 1.1 100% @30 mpk ##STR33## 0.98 27% @30 mpk______________________________________
Based on the above results, invention compounds of the present invention may be used to treat mild to moderately severe pain in warm-blooded animals, such as, humans by administration of an analgesically effective dose. The dosage range would be from about 10 to 3000 mg, in particular about 25 to 1000 mg or about 100 to 500 mg, of active ingredient 1 to 4 times per day for an average (70 kg) human although it is apparent that activity of individual compounds of the invention will vary as will the pain being treated. Pharmaceutical compositions of the invention comprise the formula (I) compounds as defined above, particularly in admixture with a pharmaceutically-acceptable carrier.
To prepare the pharmaceutical compositions of this invention, one or more compounds of the invention or salt thereof as the active ingredient, is intimately admixed with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques, which carrier may take a wide variety of forms depending of the form of preparation desired for administration, e.g., oral or parenteral such as intramuscular. In preparing the compositions in oral dosage form, any of the usual pharmaceutical media may be employed. Thus, for liquid oral preparations, such as for example, suspensions, elixirs and solutions, suitable carriers and additives include water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents and the like; for solid oral preparations such as, for example, powders, capsules and tablets, suitable carriers and additives include starches, sugars, diluents, granulating agents, lubricants, binders, disintegrating agents and the like. Because of their ease in administration, tablets and capsules represent the most advantageous oral dosage unit form, in which case solid pharmaceutical carriers are obviously employed. If desired, tablets may be sugar coated or enteric coated by standard techniques. For parenterals, the carrier will usually comprise sterile water, through other ingredients, for example, for purposes such as aiding solubility or for preservation, may be included. Injectable suspensions may also be prepared, in which case appropriate liquid carriers, suspending agents and the like may be employed. The pharmaceutical compositions herein will contain, per dosage unit, e.g., tablet, capsule, powder, injection, teaspoonful and the like, an amount of the active ingredient necessary to deliver an effective dose as described above.
The pharmaceutically acceptable salts referred to above generally take a form in which the imidazolyl ring is protonated with an inorganic or organic acid. Representative organic or inorganic acids include hydrochloric, hydrobromic, hydroiodic, perchloric, sulfuric, nitric, phosphoric, acetic, propionic, glycolic, lactic, succinic, maleic, fumaric, malic, tartaric, citric, benzoic, mandelic, methanesulfonic, hydroxyethanesulfonic, benezenesulfonic, oxalic, pamoic, 2-naphthalenesulfonic, p-toluenesulfonic, cyclohexanesulfamic, salicylic or saccharic.
The following Examples illustrate the invention:
EXAMPLE 1
4- (2-Methylthien-3-yl)methyl!-1H-imidazole Fumarate ##STR34##
To a solution of 3-bromo-2-methyl thiophene (4.2 g, 24 mmol) in 50 mL of dry Et 2 O cooled to -78° C. was added n-BuLi (15.0 mL, 24 mmol) dropwise. The bath temperature was allowed to rise to -20° C. and DMF (2.3 mL, 30 mmol) was added. The reaction mixture was allowed to warm to room temperature overnight. The reaction was quenched with NH 4 Cl (aq) and extracted with Et 2 O. The organic layer washed twice with water and brine and then dried (MgSO 4 ). After evaporation of solvent, the crude product was purified on flash silica gel (95:5 hexane/Et 2 O) to afford 2-methylthiophene-3-carboxaldehyde, A1, as a light yellow oil (1.5 g, 50%). 1 H NMR (CDCl 3 ) supported the assigned structure. ##STR35##
To a solution of N-trityl-4-iodo-imidazole (11.8 g, 27 mmol) in dry CH 2 Cl 2 (75 mL) was added EtMgBr (10.0 mL, 3.0M in Et 2 O) and the solution was stirred for 3 hrs. Then a solution of 2-methylthiophene-3-carboxaldehyde (3.3 g, 27 mmol) in CH 2 Cl 2 (20 mL) was added and the reaction mixture was stirred at room temperature overnight. The reaction was quenched with NH 4 Cl (aq) and the mixture was transferred to a separatory funnel. The aqueous layer was extracted with a second portion of CH 2 Cl 2 . The extracts were combined and washed with a small portion of water, dried (Na 2 SO 4 ), and filtered. The solvent was evaporated in vacuo to give a thick syrup which was triturated with Et 2 O to give a solid which was recrystallized with charcoal treatment from EtOAc to give (2-methylthien-3-yl)-1-trityl-imidazol-4-yl-methanol, B1. 1 H NMR (CDCl 3 ) supported the assigned structure. ##STR36##
A solution of (2-methylthien-3-yl)-1-trityl-imidazol-4-yl-methanol (1.5 g, 3.5 mmol) was combined with HCl (3.4 mmol) and Pd(OH) 2 (1.5 g) in EtOH and hydrogenated (55 psi) at 55° C. for 48 hrs. The catalyst was removed by filtration through Dicalite and the solvent was evaporated in vacuo. The residue was dissolved in water, washed twice with Et 2 O, and then basified with Na 2 CO 3 and extracted twice with EtOAc. The combined extracts were dried (K 2 CO 3 ), filtered and solvent evaporated. The residue was chromatographed on flash silica gel (99:0.75:0.25 EtOAc/MeOH/NH 4 OH) to give a thick syrup which was dissolved in 2-PrOH and combined with fumaric acid (116 mg). The solvent was evaporated and the residue recrystallized from acetone to give the target compound, m.p. 140°-141° C. 1 H NMR (DMSO-d 6 ) supported the assigned structure: δ6 2.3 (s, 3H), 3.75 (s, 2H), 6.6 (s, 2H), 6.75 (s, 1H), 6.85 (d, J=5.3 Hz, 1H), 7.15 (d, 1H), 7.65 (s, 1H). Elemental Analysis: Calc. for C 9 H 10 N 2 S.C 4 H 4 O 4 C, 53.05; H, 4.79; N, 9.52. Found C, 53.22; H, 4.87; N, 9.50.
EXAMPLE 2
4- (4-Methylthien-3-yl)methyl!-1H-imidazole Fumarate ##STR37##
To a solution of 3-bromo-4-methylthiophene (5.3 g, 30 mmol) in 100 mL of dry Et 2 O cooled to -78° C. was added n-BuLi (20.0 mL, 32 mmol) dropwise. The reaction mixture was allowed to slowly warm to -20° C. and was maintained at this temperature for 30 min. DMF (4.6 mL, 60 mmol) was added and, the reaction mixture was allowed to come to ambient temperature overnight. The reaction was quenched with aqueous ammonium chloride, and the mixture was extracted twice with Et 2 O. The organic layers were combined and washed twice with water and then brine and dried (MgSO 4 ). After filtration, the solvent was evaporated in vacuo. The residue was chromatographed on flash silica gel (98/2 hexane:Et 2 O) to give 4-methylthiophene-3-carboxaldehyde, A2, (1.9 g, 50%) as a light yellow oil. 1 H NMR (CDCl 3 ) supported the assigned structure. ##STR38##
To a solution of N-trityl-4-iodo-imidazole (11.8 g, 27 mmol) in dry CH 2 Cl 2 (75 mL) was added EtMgBr (10.0 mL, 3.0M in Et 2 O), and the solution was stirred for 3 hrs. Then a solution of 4-methylthiophene-3-carboxaldehyde (3.3 g, 27 mmol) in CH 2 Cl 2 (25 mL) was added. The reaction mixture was stirred at room temperature overnight and then was quenched with aqueous NH 4 Cl. The mixture was transferred to a separatory funnel, and the aqueous layer was extracted with a second portion of CH 2 Cl 2 . The combined extracts were washed with a small portion of water, dried (Na 2 SO 4 ), and filtered. The solvent was evaporated in vacuo to give a thick syrup which was triturated with Et 2 O to give a solid which was recrystallized with charcoal treatment from EtOAc to give (4-methylthien-3-yl)-1-trityl-imidazol-4-yl-methanol, B2. 1 H NMR (CDCl 3 ) supported the assigned structure. ##STR39##
A solution of (4-methylthien-3-yl)-1-trityl-imidazol-4-yl-methanol (2.5 g, 5.7 mmol) was combined with 1N HCl (6 mL) and Pd(OH) 2 (1.25 g) in EtOH and hydrogenated (55 psi) at 50° C. for 48 hrs. The catalyst was removed by filtration through Dicalite, and the solvent was evaporated in vacuo. The residue was dissolved in water, washed twice with Et 2 O, and then basified with Na 2 CO 3 and extracted twice with EtOAc. The combined extracts were dried (K 2 CO 3 ), filtered, and the solvent was evaporated. The residue was dissolved in 2-PrOH and combined with fumaric acid (0.57 g, 1 eq.). After standing overnight a white solid was collected and recrystallized from acetone to give the title compound m.p. 142°-144° C. 1 H NMR (DMSO-d 6 ) supported the assigned structure: δ2.15 (s, 3H), 3.75 (s, 2H), 6.6 (s, 2H), 6.75 (s, 1H), 7.05 (m, 1H), 7.15 (m, 1H), 7.65 (s, 1H). Elemental analysis: Calc. for C 9 H 10 N 2 S.C 4 H 4 O 4 C, 53.05; H, 4.79; N, 9.52. Found C, 53.03; H, 4.73; N, 9.38.
EXAMPLE 3
4- 1-(4-Methylthien-3-yl)ethyl!-1H-imidazole Fumarate ##STR40##
To a solution of (4-methylthien-3-yl)-1-trityl-imidazol-4-yl-methanol, B2, (6.5 g, 14.9 mmol) in 100 mL of CH 2 Cl 2 was added MnO 2 (13 g). The mixture was stirred at room temperature for 3 hr and then filtered through Dicalite and the solvent was evaporated in vacuo to give (4-methylthien-3-yl)-1-trityl-imidazol-4-yl-methanone, A3. 1 H NMR (CDCl 3 ) supported the assigned structure. ##STR41##
To a solution of (4-methylthien-3-yl)-1-trityl-imidazol-4-yl-methanone, A3, (6.5 g, 14.9 mmol) in 75 mL of THF was added MeMgBr (3.0M in Et 2 O) until TLC indicated complete reaction of starting material. The reaction was quenched with aqueous NH 4 Cl and extracted twice with EtOAc. The organic extracts were combined, washed with water, then dried (Na 2 SO 4 ) and filtered. The solvent was evaporated in vacuo and the residue was triturated with Et 2 O to give 1- (4-methylthien-3-yl)-1-trityl-imidazol-4-yl!-ethanol, B3. 1 H NMR (CDCl 3 ) supported the assigned structure. ##STR42##
A solution of 1- (4-methylthien-3-yl)-1-trityl-imidazol-4-yl!-ethanol, B3. (3.1 g, 6.9 mmol), 1N HCl (7.1 mL) and Pd(OH) 2 (1.75 g) in 50 mL of EtOH was hydrogenated (60 psi) at 50° C., for 60 hrs. After cooling, the catalyst was removed by filtration and solvent evaporated in vacuo. The residue was dissolved in water, and was washed twice with Et 2 O, then basified with Na 2 CO 3 and extracted twice with EtOAc. The organic extracts were combined, dried (K 2 CO 3 ), and filtered. The solvent was evaporated in vacuo and the residue was combined with fumaric acid (0.73 g, 1 eq) in 2-PrOH. A white solid was collected and recrystallized from acetone to give the target compound (1.8 g, 51%) as a white crystalline solid, m.p. 132°-134° C. 1 H NMR (DMSO-d 6 ) supported the assigned structure. δ1.5 (d, J=7.1 Hz, 3H), 2.1 (s, 3H), 4.05 (q, 1H), 6.6 (s, 2H), 6.65 (s, 1H), 7.1 (s, 2H), 7.65 (s, 1H)
Elemental analysis: Calc. for C 10 H 12 N 2 S.C 4 H 4 O 4 C, 54.53; H, 5.23; N, 9.08. Found C, 54.44; H, 5.37; N, 9.00.
EXAMPLE 4
4- 1-(4-Methylthien-3-yl)propyl!-1H-imidazole Fumarate ##STR43##
To a solution of (4-methylthien-3-yl)-1-trityl-imidazol-4-yl-methanone, A3, (2.1 g, 4.8 mmol) in 35 mL of THF was added 4.0 mL of EtMgBr (3.0M in Et 2 O). The reaction was quenched with aqueous NH 4 Cl and extracted twice with Et 2 O. The organic extracts were combined, washed with water and brine and then dried (Na 2 SO 4 ) and filtered. The solvent was evaporated in vacuo, and the residue (1- (4-methylthien-3-yl)-1-trityl-imidazol-4-yl!-propanol), A, was used directly in the next step. ##STR44##
A solution of 1- (4-methylthien-3-yl)-1-trityl-imidazol-4-yl!-propanol, A4, 1N HCl (5.0 mL) and Pd(OH) 2 (1.5 g) in 40 mL of EtOH was hydrogenated (60 psi) at 50° C. overnight. An additional 0.5 g of catalyst was added and hydrogenation was resumed overnight once again. After cooling, the catalyst was removed by filtration and solvent evaporated in vacuo. The residue was dissolved in water, and was washed twice with Et 2 O, then basified with Na 2 CO 3 and extracted twice with EtOAc. The organic extracts were combined, dried (K 2 CO 3 ), and filtered. The solvent was evaporated in vacuo, and the residue was chromatographed on flash silica gel (99:0.75:0.25 EtOAc/MeOH/NH 4 OH) to yield the title compound as a free base (0.38 g, 38% for 2 steps). This was combined with fumaric acid (0.21 g) in 2-PrOH and the solvent was evaporated in vacuo. The residue was recrystallized from acetone to give the target compound (0.30 g) as a white crystalline solid, m.p. 101°-105° C. 1 H NMR (DMSO-d 6 ) supported the assigned structure. δ0.85 (t, 3H), 1.95 (m, 2H), 2.15 (s, 3H), 3.85 (t, 1H), 6.6 (s, 2H), 6.75 (s, 1H), 7.05 (m, 1H), 7.15 (m, 1H), 7.65 (s, 1H). Elemental analysis: Calc. for C 11 H 14 N 2 S.C 4 H 4 O 4 C, 55.89; H, 5.63; N, 8.69. Found C, 55.87; H, 5.69; N, 8.56
EXAMPLE 5
4- (2,5-dimethylthien-3-yl)methyl!-1H-imidazole Fumarate ##STR45##
To a solution of N-trityl-4-iodo-imidazole (11.8 g, 27 mmol) in dry CH 2 Cl 2 (200 mL) was added EtMgBr (11.0 mL, 3.0M in Et 2 O). After complete halogen-metal exchange this solution was cannulated into a solution of 2,5-dimethylthiophene-3-carboxaldehyde (3.5 g, 25 mmol) in 50 mL of CH 2 Cl 2 . The reaction mixture was stirred at room temperature for 1 hr and then quenched with aqueous NH 4 Cl. The mixture was transferred to a separatory funnel and the aqueous layer was extracted with a second portion of CH 2 Cl 2 . The combined extracts were dried (MgSO 4 ) and filtered. The solvent was evaporated in vacuo to give a thick syrup which was triturated with Et 2 O to give a solid which was recrystallized from acetone to give (2,5-dimethylthien-3-yl)-1-trityl-imidazol-4-yl-methanol, A5. 1 H NMR (CDCl 3 ) supported the assigned structure. ##STR46##
A solution of (2,5-dimethylthien-3-yl)-1-trityl-imidazol-4-yl!-methanol, A5, (3.4 g, 6.9 mmol), concentrated HCl (0.31 g) and Pd(OH) 2 (1.75 g) in 40 mL of 95% EtOH was hydrogenated (60 psi) at 50° C., for 60 hrs. After cooling, the catalyst was removed by filtration and solvent evaporated in vacuo. The residue was dissolved in water, and was washed twice with Et 2 O, then basified with Na 2 CO 3 and extracted twice with EtOAc. The organic extracts were combined, dried (K 2 CO 3 ), and filtered. The solvent was evaporated in vacuo and the residue was combined with fumaric acid in 2-PrOH. A white solid was collected and recrystallized from acetone to give the target compound (0.63 g, 27%) as a white crystalline solid m.p. 148°-149° C. 1 H NMR (DMSO-d 6 ) supported the assigned structure. δ2.37 (s, 3H), 2.39 (s, 3H), 3.65 (s, 2H), 6.6 (s, 2H), 6.7 (s, 1H), 7.65 (s, 1H).
Elemental analysis: Calc. for C 10 H 12 N 2 S.C 4 H 4 O 4 C, 54.53; H, 5.23; N, 9.08. Found C, 54.74; H, 5.10; N, 9.00.
EXAMPLE 6
4- (2,5-diethylthien-3-yl)methyl!-1H-imidazole Fumarate ##STR47##
To a mixture of 2-ethylthiophene (56.1 g, 0.5 mol) and acetic anhydride (59 mL) cooled in an ice bath was added 1 mL of HClO 4 . The reaction mixture became quite dark and there was a vigorous exothermic reaction. After 1 hr, the mixture was diluted with CH 2 Cl 2 and poured onto ice/NaHCO 3 . This mixture was transferred to a separatory funnel, and the organic layer was washed with an additional portion of dilute NaHCO 3 , water, dried (MgSO 4 ) and filtered. The solvent was evaporated in vacuo to give a brown oil which was distilled in vacuo (6-8 mm Hg). The product, A6, was collected at 120°-121° C. as a colorless liquid. 1 H NMR (CDCl 3 ) supported the assigned structure. ##STR48##
5-Ethyl-2-acetythiophene, A6, (18.5 g, 0.12 mol) was added to hydrazine hydrate (30.0 mL) in 75 mL of ethylene glycol, and the mixture was heated in an oil bath to 170° C. The excess hydrazine and water were distilled out of the reaction mixture. After cooling to room temperature, KOH (24.9 g, 0.44 mol) was added and again the mixture was heated in an oil bath to 120° C., at which point a vigorous reaction and gas evolution began. Heating at 120°-130° C. was continued as the product was distilled from the reaction mixture. The distillate was extracted twice with Et 2 O. The extracts were then combined and washed with 3N HCl, water and finally brine and then dried (MgSO 4 ) and filtered. The solvent was evaporated in vacuo and the residue was distilled at ambient pressure (175°-177° C.) to give 2,5-diethylthiophene, B6, (10.3 g, 61%) as a colorless liquid. 1 H NMR (CDCl 3 ) supported the assigned structure. ##STR49##
A solution of Br 2 (6.4 g, 40.0 mmol) in CHCl 3 (25 mL) was added dropwise to a solution of 2,5-diethylthiophene, B6, (5.6 g, 40 mmol) in CHCl 3 (75 mL). The reaction was stirred for 2 hrs at room temperature and then poured onto ice/NaHSO 3 . The organic layer was then washed with saturated NaHCO 3 , and then water and then dried (MgSO 4 ) and filtered. The solvent was evaporated in vacuo and the residue was distilled at reduced pressure (1 mm Hg) and 3-bromo-2,5-diethylthiophene, C6, was collected as 5.0 g (57%) of a clear liquid b.p. 79°-81° C. @ 1 mm Hg. 1 H NMR (CDCl 3 ) supported the assigned structure. ##STR50##
To a solution of 3-bromo-2,5-diethyl thiophene, C6, (9.1 g, 41 mmol) in 100 mL of dry Et 2 O cooled to -78° C. was added n-BuLi (26.2 mL, 42 mmol) dropwise. The bath temperature was allowed to rise to -20° C. and DMF (6.3 mL, 82 mmol) was added. The reaction mixture was allowed to warm to room temperature overnight. The reaction was quenched with NH 4 Cl (aq) and extracted with Et 2 O. The organic layer washed twice with water and brine and then dried (MgSO 4 ). After evaporation of solvent, the crude product was purified on flash silica gel (98:2 hexane/Et 2 O) to afford 2,5-diethylthiophene-3-carboxaldehyde, D6, as a light yellow oil (5.0 g, 72%). 1 H NMR (CDCl 3 ) supported the assigned structure. ##STR51##
To a solution of N-trityl-4-iodo-imidazole (13.5 g, 31 mmol) in dry CH 2 Cl 2 (75 mL) was added EtMgBr (10.0 mL, 3.0M in Et 2 O) and the solution was stirred for 3 hrs. Then a solution of 2,5-diethylthiophene-3-carboxaldehyde, D6, (5.0 g, 30 mmol) in CH 2 Cl 2 (20 mL) was added, and the reaction mixture was stirred at room temperature overnight. The reaction was quenched with NH 4 Cl (aq) and the mixture was transferred to a separatory funnel. The aqueous layer was extracted with a second portion of CH 2 Cl 2 . The extracts were combined and washed with a small portion of water, dried (Na 2 SO 4 ), and filtered. The solvent was evaporated in vacuo to give a thick syrup which was triturated with Et 2 O to give a solid which was recrystallized from EtOAc to give (2,5-diethylthien-3-yl)-1-trityl-imidazol-4-yl-methanol, E6. 1 H NMR (CDCl 3 ) supported the assigned structure. ##STR52##
To a solution of TFA (9.2 mL, 120 mmol) in dry CH 2 Cl 2 (50 mL) cooled in an ice bath, was added BH 3 .Me 2 S (90.0 mL, 1.0M in CH 2 Cl 2 ) dropwise. This was stirred at 0° C. for an additional 90 min and then (2,5-diethylthien-3-yl)-1-trityl-imidazol-4-yl!-methanol, E6, (1.4 g, 3 mmol) in CH 2 Cl 2 (25 mL) was added in one portion and reaction mixture was allowed to come to room temperature overnight. The reaction was quenched by the addition of 100 mL of 3:1 MeOH/3N HCl followed by refluxing for 2 hrs. Most of the solvent was then evaporated in vacuo. The residue was dissolved in water and washed twice with Et 2 O, then basified with Na 2 CO 3 and extracted twice with EtOAc. The organic extracts were combined, dried (K 2 CO 3 ) and filtered. The solvent was evaporated in vacuo to give a syrup (0.69 g), which was combined with fumaric acid (0.36 g) in MeOH. The solvent was evaporated and the residue was recrystallized from acetone to give the title compound (0.70 g, 70%) as a white solid, m.p. 115°-116.5° C. 1 H NMR (DMSO-d 6 ) supported the assigned structure: 1.2 (m, 6H), 2.7 (m, 4H), 3.7 (s, 2H), 6.55 (s, 1H), 6.6 (s, 2H), 6.75 (s, 1H), 7.6 (s, 1H). Elemental Analysis: Calc for C 12 H 16 N 2 S.C 4 H 4 O 4 C, 57.13; H, 5.99; N, 8.33. Found C, 57.06; H, 6.06; N 8.27.
EXAMPLE 7
4- (2-Ethylthien-3-yl)methyl!-1H-imidazole Fumarate ##STR53##
To a mixture of 2-ethylthiophene (11.2 g, 0.100 mol) and sodium acetate (16.4 g, 0.200 mol) in 75 mL of water was added bromine (32.0 g, 0.200 mol). The reaction mixture was stirred for 2 days. GC analysis indicated that some monobrominated material was left so additional bromine (7.75 g) and sodium acetate (5.00 g) were added. After a few hours of stirring, GC analysis indicated that the monobromo material was gone so zinc (19.6 g, 0.30 mol) was added in portions. The reaction mixture was then refluxed for 25 h. The product was distilled out of the reaction mixture. The distillate was extracted with ether twice. The ether extracts were combined, washed with aqueous sodium bicarbonate, water, and brine, and then dried (MgSO 4 ). The solution was concentrated in vacuo, and then distilled under reduced pressure to provide 10.1 g (53%) of 3-bromo-2-ethylthiophene, A7, b.p. 49°-50° C. @ 4mmHg. The 1 H NMR in CDCl 3 supported the desired product structure. ##STR54##
A solution of 3-bromo-2-ethylthiophene, A7, (8.9 g, 0.0465 mol) in 50 mL of diethyl ether was cooled to -78° C., and a solution of n-BuLi (29.0 mL, 1.6M) in hexanes was added dropwise. When the addition was complete, the reaction was stirred at -78° C. for 5 min. Then DMF (5.1 g, 0.070 mol) was cannulated into the reaction mixture which was allowed to warm to ambient temperature and was stirred overnight. The reaction was quenched with water and extracted twice with diethyl ether. The organic extracts were combined, washed with twice with water and then brine and dried (MgSO 4 ). The solution was filtered and concentrated to provide an oil which was purified on flash silica gel with 97.5:2.5 hexanes:diethyl ether to give 1.66 g (25%) of 2-ethylthiophene-3-carboxaldehyde, B7. The 1 H NMR in CDCl 3 supported the desired product structure. ##STR55##
To a solution of N-trityl-4-iodo-imidazole (4.1 g, 0.0095 mol) in dry CH 2 Cl 2 (75 mL) was added a solution of MeMgBr (4.0 mL, 3.0M) in diethyl ether and the solution was stirred for 3 hrs. Then a solution of 2-ethylthiophene-3-carboxaldehyde, B7, (1.66 g, 0.0087 mol) in CH 2 Cl 2 (20 mL) was added and the reaction mixture was stirred at room temperature overnight. The reaction was quenched with aqueous NH 4 Cl and the mixture was transferred to a separatory funnel. The aqueous layer was extracted with a second portion of CH 2 Cl 2 . The extracts were combined and washed with a small portion of water, dried (Na 2 SO 4 ), and filtered. The solvent was evaporated in vacuo, and the residue was triturated with Et 2 O to give (2-ethylthien-3-yl)-1-trityl-imidazol-4-yl-methanol, C7, as a beige solid which was taken on to the next step directly. ##STR56##
A solution of (2-methylthien-3-yl)-1-trityl-imidazol-4-yl-methanol, C7, (0.9 g, 0.00199 mol) was combined with 1N HCl (2.0 mL) and Pd(OH) 2 (1.5 g) in EtOH and hydrogenated (55 psi) at 50° C. for 48 hrs. The catalyst was removed by filtration through Dicalite, and the solvent was evaporated in vacuo. The residue was dissolved in water, washed twice with Et 2 O, and then basified with Na 2 CO 3 and extracted twice with EtOAc. The combined extracts were dried (K 2 CO 3 ), filtered and solvent evaporated. The residue was dissolved in 2-PrOH and combined with fumaric acid. The solvent was evaporated and the residue recrystallized from acetone to provide 4- (2-ethylthien-3-yl)methyl!-1H-imidazole fumarate, Cp-7, as a white solid, m.p. 132°-134° C. 1 H NMR (DMSO-d6) supported the assigned structure: δ1.20 (t, J=7.5 Hz, 3H), 2.8 (q, J=7.5 Hz, 2H), 3.80 (s, 2H), 6.65 (s, 2H), 6.70 (s, 1H), 6.80 (d, 1H), 7.20 (d, 2H), 7.60 (s, 1H). Elemental Analysis: Calc. for C 10 H 12 N 2 S.C 4 H 4 O 4 C, 54.33; H, 5.23; N, 9.09. Found C, 54.42; H, 5.17; N, 9.02.
EXAMPLE 8
4- (2,4-Dimethylthien-3-yl)methyl!-1H-imidazole Fumarate ##STR57##
A solution of 2,4,5-tribromo-3-methylthiophene (50.2 g, 0.15 mol; Gronowitz, S.; Moses, P. Hakansson Arkiv. f. Kemi. 1960, 14, 267) in 400 mL of diethyl ether was cooled to -78° C., and a solution of nBuLi (100 mL, 1.6M) was added dropwise. The starting material precipitated out of solution, but when n-BuLi added, the reaction mixture became stirrable again. When the addition was complete, the reaction mixture was stirred for 20 min, and then a solution of dimethyl sulfate (75.7 g, 0.600 mol) in 200 mL of diethyl ether which was cooled to -50° C. was added by cannulation. When addition was complete, the reaction mixture was allowed to warm to ambient temperature and was stirred overnight. The reaction was quenched with 100 mL of 6N NaOH solution and stirred for 2h. The mixture was transferred to a separatory funnel, and the aqueous layer was separated and extracted with additional ether. The organic layers were combined, washed with water and brine and dried (MgSO 4 ). The suspension was filtered and concentrated to give an oil. Vacuum distillation provided 22.1 g (55%) of 2,4-dibromo-3,5-dimethylthiophene, A8, b.p. 71°-72° C. @ 0.4 mmHg. The 1 H NMR in CDCl 3 supported the assigned structure. ##STR58##
A solution of 2,4-dibromo-3,5-dimethylthiophene, A8, (22.0 g, 0.081 mol) in 250 mL of THF was cooled to -78° C. Then a solution of n-BuLi (53 mL, 1.6M) in hexanes was cooled to -78° C. and added via cannulation. The reaction was stirred for 3 h, and then was quenched with aqueous ammonium chloride. The mixture was extracted twice with diethyl ether. The organic layers were combined, washed with water and brine and dried (MgSO 4 ). The suspension was filtered and concentrated to give an oil. Vacuum distillation provided 7.6 g (49%) of 3-dibromo-2,4-dimethyl thiophene, B8, b.p. 77°-79° C. @ 5 mmHg, as a nearly colorless liquid. The 1 H NMR in CDCl 3 supported the assigned structure. ##STR59##
A solution of 3-bromo-2,4-dimethylthiophene, B8, (5.9 g, 0.031 mol) in 200 mL of diethyl ether was cooled to -78° C., and a solution of n-BuLi (25.0 mL, 1.6M) in hexanes was added dropwise. When the addition was complete, the reaction was stirred at -78° C. for 4 h. TLC analysis indicated very little conversion so reaction mixture was warmed slowly to -25° C. Then a solution of DMF (4.5 g, 0.062 mol) in 25 mL of ether was cannulated into the reaction mixture which was allowed to warm to ambient temperature and was stirred overnight. The reaction was quenched with water and extracted twice with diethyl ether. The organic extracts were combined, washed with twice with water and then brine and dried (MgSO 4 ). The solution was filtered and concentrated to provide an amber oil which was dissolved in hexane. The solution was treated with charcoal, filtered through Dicalite, and concentrated to give 2,4-dimethylthiophene-3-carboxaldehyde, C,8, which was used directly in the next step. ##STR60##
To a solution of 4-iodo-1-trityl imidazole (11.8 g, 0.027 mol) in 75 mL of dry dichloromethane under nitrogen was added dropwise a solution of methyl magnesium bromide in diethyl ether (9.0 mL, 3.0M). When addition was complete, the reaction mixture was stirred for 1 h at 25° C. Then, 2,4-dimethylthiophene-3-carboxaldehyde, C8, (3.8 g, 0.027 mol) was added as a solution in 20 mL of dichloromethane. After overnight stirring at ambient temperature, the reaction was quenched with saturated ammonium chloride solution. The layers were separated, and the aqueous layer was extracted again with dichloromethane. The organic layers were combined, dried (Na 2 SO 4 ), and concentrated in vacuo. The residue was triturated with ethyl acetate to provide (2,4-dimethylthieno-3-yl)-1-trityl-imidazol-4yl-methanol, D8, as an off-white solid which was taken on directly in the next step. ##STR61##
A solution of BH 3 .Me 2 S (120 mL, 1.0M) in dichloromethane was added dropwise to a solution of TFA (18.2 g, 0.16 mol) in 50 mL of dry dichloromethane at 0° C. When the addition was complete, the reaction mixture was stirred for 2 h. Then the carbinol, D8, (1.8 g, 0.040 mol) was added, and the reaction mixture was warmed to ambient temperature and stirred overnight. The reaction was quenched with 100 mL of 1.5N HCl, and then the mixture was refluxed on a steam bath for 2 h. The solution was cooled and then concentrated in vacuo to provide a brown oil. The residue was dissolved in water. This solution was washed twice with ether, basified with Na 2 CO 3 and extracted with ethyl acetate. The ethyl acetate extracts were combined, dried (Na 2 SO 4 ), and concentrated in vacuo. The residue was purified on flash silica gel using 97.5:2.5 chloroform: 10% ammonium hydroxide in methanol. The isolated material was dissolved in isopropanol, and fumaric acid was added. The solvent was removed under reduced pressure, and the residue was recrystallized from acetone to provide 0.274 g of 4- -(2,4-dimethylthien-3-yl)methyl!-1H-imidazole fumarate, Cp-8, as a white solid, m.p. 160°-162° C. The 1 H NMR in DMSO-d 6 supported the assigned structure: δ2.10 (s, 3H, Me), 2.40 (s, 3H, Me), 3.70 (s, 2H, CH 2 ), 6.55 (s, 1H), 6.65 (s, 2H), 6.85 (s, 1H), 7.60 (s, 1H). Elemental analysis: Calculated for C 10 H 12 N 2 S.C 4 H 4 O 4 : C, 54.54; H, 5.23; N, 9.08. Found C, 54.45; H, 5.26; N, 9.06.
EXAMPLE 9
4- (4-Ethylthien-3-yl)methyl!-1H-imidazole Fumarate ##STR62##
To an ice-cooled solution of 3-ethylthiophene (25.75 g, 0.23 mol) in 75 mL of chloroform was added bromine (111.87 g, 0.7 mol). The reaction mixture was allowed to warm to ambient temperature and was left to stir overnight. Analysis by GC indicated that >90% of a single product was present so the reaction mixture was poured onto ice. The mixture was transferred to a separatory funnel and diluted with additional chloroform. The layers were separated and the organic layer was washed with 200 mL of 10% NaHSO 3 solution, water, and brine, and dried (MgSO 4 ). After filtration, concentration in vacuo provided a dark oil which was distilled under reduced pressure to provide 2,3,5-tribromo-4-ethylthiophene, A9. GC analysis indicated that the product was reasonably pure and it was taken on directly. ##STR63##
A suspension of zinc (24.5 g, 0.375 mol) in 250 mL of 10% aqueous acetic acid was placed in a round bottom flask fitted with a mechanical stirrer. The suspension was heated at reflux, and 2,3,5-tribromo-4-ethylthiophene, A9, (26.1 g, 0.0750 mol) was added in portions. Reflux was continued overnight, and then the product was removed by steam distillation. The distillate was transferred to a separatory funnel and extracted twice with ether. The ether layers were combined, washed with saturated sodium bicarbonate solution, and dried (MgSO4). After filtration, the solution was concentrated to give 7 g of a clear oil. The original reaction pot was resubjected to steam distillation to provide a second batch of product. Both batches contained a mixture of desired product and dibromo compound. These were purified on flash silica gel with pentane as eluant to provide 3.4 g of 3-bromo-4-ethylthiophene, B9, as a clear liquid. This material was taken on directly in the next step. ##STR64##
A solution of 3-bromo-4-ethylthiophene, B9, (3.4 g, 0.018 mol) in 40 mL of diethyl ether was cooled to -78° C., and a solution of n-BuLi (12.0 mL, 1.6M) in hexanes was added dropwise. The solution was allowed to warm to -20° C., and DMF (1.46 g, 0.020 mol) was added. The reaction mixture was allowed to warm to ambient temperature and was stirred overnight. The reaction was quenched with aqueous ammonium chloride solution and extracted twice with diethyl ether. The organic extracts were combined, washed with twice with water and then brine and dried (MgSO 4 ). The solution was filtered and concentrated to provide 4-ethylthiophene-3-carboxaldehyde, C9, which was used directly in the next step. ##STR65##
To a solution of 4-iodo-1-trityl imidazole (3.9 g, 0.0090 mol) in 40 mL of dry dichloromethane under nitrogen was added dropwise a solution of ethyl magnesium bromide in diethyl ether (3.0 mL, 3.0M). When addition was complete, the reaction mixture was stirred for 1 h at 25° C. Then, 4-ethyl-thiophene-3-carboxaldehyde, C9, (1.2 g, 0.0086 mol) was added as a solution in 20 mL of dichloromethane. After overnight stirring at ambient temperature, the reaction was quenched with saturated ammonium chloride solution. The layers were separated, and the aqueous layer was extracted again with dichloromethane. The organic layers were combined, dried (Na 2 SO 4 ), and concentrated to provide an orange-yellow solid. This material was recrystallized from ethyl acetate to provide (4-ethylthiophen-3-yl)1-trityl-imidazo-4-yl-methanol, D9, which was taken on directly in the next step. ##STR66##
A solution of (4-ethylthien-3-yl)-1-trityl-imidazol-4-yl-methanol, D9, in 40 mL of ethanol containing 1N hydrochloric acid (1.7 mL) and palladium hydroxide (0.75 g) was shaken with hydrogen at 60 psi at 50° C. on a Parr hydrogenator for 3 days. The solution was cooled and filtered to remove the catalyst. The filtrate was concentrated under reduced pressure. The residue was dissolved in water and extracted twice with Et 2 O then basified with sodium carbonate and extracted with ethyl acetate. The organic layers were combined, dried (K 2 CO 3 ), and concentrated in vacuo. The residue was dissolved in 2-propanol and fumaric acid was added. The solution was concentrated in vacuo, and the residue was recrystallized from acetone to provide 0.245 g of 4- (4-ethylthien-3-yl)methyl!-1H-imidazole fumarate, C-9, as a white solid, m.p. 142°-144° C. The 1 H NMR in DMSO-d 6 supported the assigned structure: δ1.20 (t, 3H, Me), 3.8 (s, 2H), 6.65 (s, 2H), 6.67 (s, 1H), 7.05 (m, 1H), 7.10 (m, 1H), 7.60 (s, 1H), 7.55 (s, 1H). Elemental analysis: Calculated for C 10 H 12 N 2 S.C 4 H 4 O 4 : C, 54.53; H, 5.23; N, 9.08. Found C, 54.58; H, 5.33; N, 9.03.
EXAMPLE 10
4- (4-Ethylthien-3-yl)ethyl!-1H-imidazole Fumarate ##STR67##
To a solution of the carbinol, D9, (1.17 g, 2.6 mmol) in 50 mL of dichloromethane was added MnO 2 (5.0 g). The reaction mixture was stirred overnight and then was filtered. The filtrate was concentrated in vacuo to provide 4-(4-ethylthien-3yl)-1-trityl-imidazol-4yl methanone, A10, which was used directly in the next step. ##STR68##
A solution of methylmagnesium bromide (1.0 mL, 3.0M) in diethyl ether was added to an ice-cooled solution of 4-(4-ethylthien-3-yl)-1-trityl-imidazol-4yl methanone, A10, (1.17 g, 0.0026 mol) in 25 mL of THF. After 30 min of stirring, TLC analysis indicated that some starting material was left so an additional 1.0 mL of methylmagnesium bromide was added, and the reaction mixture was stirred over the weekend. The reaction was quenched with aqueous ammonium chloride solution, and the resulting mixture was extracted twice with ethyl acetate. The ethyl acetate extracts were combined, washed with water and brine, dried (Na 2 SO 4 ), and filtered. Concentration provided 1-(4-ethylthien-3-yl)-1-trityl-imidazol-4-yl ethanol, B10, as an oil which crystallized on standing. This material was taken on directly in the next step. ##STR69##
A solution of 1- (4-ethylthien-3-yl)-1-trityl-imidaz-4-yl!-ethanol, B10, in 40 mL of ethanol containing 1N hydrochloric acid (2.5 mL) and palladium hydroxide (1.0 g) was shaken with hydrogen at 60 psi at 50° C. on a Parr hydrogenator for 3 days. The solution was cooled and filtered to remove the catalyst. The filtrate was concentrated under reduced pressure. The residue was dissolved in water and extracted twice with Et 2 O, then basified with sodium carbonate and extracted with ethyl acetate. The organic layers were combined, dried (K 2 CO 3 ), and concentrated in vacuo. The residue was purified on a silica gel column on a Foxy apparatus using 99:0.75:0.25 ethyl acetate:methanol:ammonium hydroxide as eluant to provide a glass. This material was dissolved in 2-propanol and fumaric acid was added. The solution was concentrated in vacuo, and the residue was recrystallized from acetone to provide 0.323 g of 4- 1-(4-ethylthien-3-yl)ethyl!-1H-imidazole fumarate, Cp-10, as a white solid, m.p. 145°-147° C. The 1 H NMR in DMSO-d 6 supported the assigned structure: δ1.50 (t, 3H, Me), 1.50 (d, 2H, Me), 4.05 (q, 1H, CH), 6.60 (s, 3H), 7.05 (d, 1H), 7.15 (d, 1H), 7.55 (s, 1H). Elemental analysis: Calculated for C 11 H 14 N 2 S.C 4 H 4 O 4 : C, 55.89; H, 5.63; N, 8.69. Found C, 55.79; H, 5.47; N, 8.59. | Described herein are 4- (thien-3-yl)methyl!-imidazoles of the formula: ##STR1## wherein R is hydrogen or methyl, and
X is C 1-4 alkyl, bromine or chlorine; or ##STR2## wherein Y is hydrogen, C 1-4 alkyl, bromine or chlorine, and
Z is C 1-4 4alkyl, bromine or chlorine which have exceptional analgesic activity. | 2 |
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a National Phase of PCT/EP2012/073181, filed 21 Nov. 2012, which claims priority from EP No. 11190133.6, filed 22 Nov. 2011, U.S. Application No. 61/562,626, filed 22 Nov. 2011 and Italian Application No. MI2012A000146, filed 3 Feb. 2012, the specifications of which are all incorporated herein by reference.
FIELD OF THE INVENTION
The present invention relates to a process for the synthesis of drospirenone.
BACKGROUND OF THE INVENTION
The compound of formula 1 below, the chemical name of which is 6β,7β;15β,16β-dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone, is commonly known as drospirenone, also abbreviated as DRSP (abbreviation used in the remainder of the text):
Drospirenone is a synthetic steroid with progestogenic, antimineralocorticoid and antiandrogenic activity; thanks to these characteristics, drospirenone has been used for some time in the preparation of pharmaceutical compositions with contraceptive action for oral administration.
Many processes for the preparation of drospirenone are known in literature.
European patent EP 75189 B1 describes a process which, through various steps commencing from 3β,7α,15α-trihydroxy-5-androsten-17-one, reaches the intermediate 17α-(3-hydroxypropyl)-6β,7β;15β,16β-dimethylene-5β-androstane-3β,5,17β-triol (also simply referred to as “triol” in the remainder of the text), from which the end product drospirenone is obtained by hot oxidation with the pyridine/water/chromium trioxide mixture (Collins reagent). The latter step constitutes the main disadvantage of the process: indeed, like all Cr(VI) compounds, chromium trioxide is a known carcinogen, the use of which is subject to legislative restrictions such that the precautions required during the use and disposal of these products make them virtually unusable. Moreover, the formation of drospirenone in the presence of chromium trioxide generates a series of impurities that reduce the reaction yield, as highlighted in patent EP 918791 B1.
In patent EP 918791 B1 it is disclosed a process that avoids the use of the Collins reagent. In this process, it is employed an oxidant system comprising an oxidizing agent such as sodium bromate and a ruthenium salt as oxidation catalyst; the product of oxidation of the triol is the compound 6β,7β;15β,16β-dimethylene-5β-hydroxy-3-oxo-17α-androstane-21,17-carbolactone, that is generally known in the field with the abbreviation 5β-OH-DRSP (abbreviation that will be used in the following description); this compound is then converted into DRSP by elimination of a water molecule between the positions 4 and 5 of the steroidal skeleton, by means of para-toluenesulfonic acid. This process too envisages the purification of drospirenone by chromatography as in EP 75189 B1. The purity of the raw drospirenone obtained by the method described in EP 918791 B1 is of 93%, a value that is far from acceptable for a pharmaceutical product. The method of EP 918791 B1 thus requires purification by means of chromatography of the crude product downstream the production process. The industrial-scale purification, by means of chromatography, of a product having a market of thousands of kg/year, is however a very significant commitment: a dedicated plant with the use of tons of silica gel, which must then be disposed of and thousands of cubic meters of solvent are required, with a huge economic commitment for the set-up and management logistics of said plant.
The above problem is overcome by the process described in patent EP 1828222 B1, in the name of the Applicant. According to the process of this patent, the crude drospirenone is obtained by the intermediate 17α-(3-hydroxypropyl)-6β,7β;15β,16β-dimethylene-5β-androstane-3β,5,17β-triol, using an hypochlorite of an alkali or alkaline-earth metal (for example calcium hypochlorite) in the presence, as catalyst, of 2,2,6,6-tetramethylpiperidine-1-oxyl radical (known as TEMPO in the field) or derivatives thereof; at the end of this reaction, a mixture of compounds is obtained, containing 5β-OH-DRSP as the main component. An acid (for example para-toluenesulfonic acid) is added to this mixture as dehydrating agent; the drospirenone obtained by this preparation route is brought to pharmaceutical grade by crystallization.
The process of EP 1828222 B1 already resolves many of the problems of the known prior art, but still requires the use of an acid, in particular para-toluenesulfonic acid, in the final phase of synthesis. It is known, from Tetrahedron Letters 27(45), 5463-5466, 1986 for example, that drospirenone is unstable to acids: the lactone ring in position 17,21 and the three-membered ring in position 6,7 are not stable in the presence of acids, reacting to give impurities that must therefore be eliminated; this complicates the overall production process of drospirenone and reduces the yields thereof.
Finally, in patent EP 1571153 B1 is disclosed a further possible method for the production of DRSP. Example 11 of this patent describes a process in which: the two carbolactols corresponding to 5β-OH-DRSP, dissolved in methylene chloride, are added to a 5% (by weight) aqueous solution of sodium bicarbonate; calcium hypochlorite, in the presence of TEMPO as catalyst, is added to the biphasic mixture containing the carbolactols; pyridine is then added, and methylene chloride is distilled at room pressure; at the end of the distillation, the reaction mixture is kept hot (that is, at the temperature of methylene chloride distillation), the solvent is distilled under reduced pressure, and the crude reaction product is first chromatographed over silica gel and finally crystallized. Also this procedure suffers from some drawbacks. In first place, it still requires, as most of the previous methods, a final step of chromatography for the isolation of the desired product; chromatography, as discussed below, is undesired in an industrial process, because it prolongs the time of production and entails the use and disposal of huge amounts of solvents and silica. Besides, in the method described in this example, the maximum temperature reached is about 40° C., namely, boiling point of methylene chloride, reached during its distillation at room pressure; this temperature cannot be overcome in this procedure, because at higher temperatures sodium bicarbonate, still present in the mixture, starts to transform into sodium carbonate, with an increase in the pH of the mixture; the higher pH caused by sodium carbonate is capable to open the lactone ring of 5β-OH-DRSP, leading to by-products and in the end to a lower yield in desired product. The relatively low temperatures taught in this example of EP 1571153 B1, however, do not afford satisfactory yields in drospirenone. The yield of drospirenone, calculated starting from 17α-(3-hydroxypropyl)-6β,7β;15β,16β-dimethylene-5β-androstane-3β,5,17β-triol (combined yield of examples 7, production of the carbolactols, and 11, oxidation of the carbolactols) is 62%.
It is therefore an object of the present invention to provide an improved process for the production of drospirenone.
In particular, object of the present invention is to provide a process that avoids the need to use toxic or carcinogenic metals in the oxidation reaction of 17α-(3-hydroxypropyl)-6β,7β;15β,16β-dimethylene-5β-androstane-3β,5,17β-triol as well as the need to use acids in the dehydration of 5β-OH-DRSP that forms the drospirenone, thus allowing an increase in the yield of the end product.
SUMMARY OF THE INVENTION
These objects are achieved with the present invention with a process that comprises the following steps:
a) oxidation of the compound 17α-(3-hydroxypropyl)-6β,7β;15β,16β-dimethylene-5β-androstane-3β,5,17β-triol with an oxidizing agent in the presence of a catalytic amount of 2,2,6,6-tetramethylpiperidine-1-oxyl radical or a derivative thereof; b) removal of the solvent from the reaction mixture by distillation, obtaining a raw oily product containing 6β,7β;15β,16β-dimethylene-5β-hydroxy-3-oxo-17α-androstane-21,17-carbolactone; c) addition to said raw oily product of a mixture of water and an organic base and heating of the resulting mixture at a temperature comprised between 45 and 90° C., to form drospirenone.
DETAILED DESCRIPTION OF THE INVENTION
The starting compound of the process of the invention is 17α-(3-hydroxypropyl)-6β,7β;15β,16β-dimethylene-5β-androstane-3β,5,17β-triol. This compound can be prepared according to any known method; preferably, said compound is prepared according to the procedure described in patent EP 1828222 B1 or according to a similar procedure.
The starting compound is then oxidised according to the procedure described in patent EP 1828222 B1, with a suitable oxidising agent in the presence of catalytic amounts of the 2,2,6,6-tetramethylpiperidine-1-oxyl radical or a derivative thereof. Oxidation of the triol could also be achieved according to the procedure described in Italian patent application MI2011A991383 in the name of the Applicant, filed on 25 Jul. 2011, and the contents of which were made public by means of publication in an extended abstract of the application itself at the following web address:
http://www.chemogroup.com/EN/news/Drospirenone979.pdf
The oxidation procedure of EP 1828222 B1 is however preferred, and the description that follows makes reference to the method of said patent.
With “suitable oxidising agent” it is meant a compound selected among the hypohalides of alkali and alkaline-earth metals, iodine, oxygen in the presence of CuCl, potassium peroxymonosulphate (KHSO 5 ), known commercially as Oxone®, and 1,3,5-trichloro-2,4,6-triazinetrione; the preferred oxidising agents are calcium or sodium hypochlorite. The oxidising agent is employed in an amount, measured in equivalents, at least equal to 3 times the number of moles of the triol to be oxidised, and preferably at least equal to 3.3 times the moles of said triol.
The catalyst employed is selected among the 2,2,6,6-tetramethylpiperidine-1-oxyl radical, known as TEMPO, or derivatives thereof, such as the 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl radical, the 4-methoxy-2,2,6,6-tetramethyl piperidine-1-oxyl radical, the 4-benzoyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl radical, the 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxyl radical, the 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl radical, the 4-carboxy-2,2,6,6-tetramethylpiperidine-1-oxyl radical, the 4-cyano-2,2,6,6-tetramethylpiperidine-1-oxyl radical, and the 4-oxo-2,2,6,6-tetramethylpiperidine-1-oxyl radical.
The catalyst is preferably employed in a molar amount comprised between about 5 and 15% of the moles of the triol to be oxidised; the inventors have observed that with molar amounts below 5% the reaction only takes place with limited yields, while molar amounts above 15% do not result in increased yield and would therefore constitute a waste of catalyst.
The reaction is carried out in an organic solvent chosen among acetone, ethers, such as for example methyl tert-butyl ether and tetrahydrofuran, esters such as for example ethyl acetate, hydrocarbons such as for example toluene, halogenated hydrocarbons such as methylene chloride and mixtures of these solvents, at a temperature comprised between 0 and 40° C., preferably between 10 and 30° C.
Preferred conditions for the oxidation reaction are the use of calcium hypochlorite in a mixture of methylene chloride/tetrahydrofuran (preferably in a volume ratio of at least 10/1) as solvent, at a temperature comprised between 20 and 30° C., in the presence of TEMPO radical between about 10% and 14% in moles (with respect to the triol) and in the presence of an aqueous solution of sodium bicarbonate.
The mixture obtained at the end of the oxidation reaction is subjected to the usual treatments for the recovery of an organic compound from an organic mixture, such as washing with water-based solutions and filtering, and lastly to distillation to remove the solvent.
On completion of the distillation, an oily product is obtained, which is not further purified. This product is an oily mixture containing mainly the compound 6β,7β;15β,16β-dimethylene-5β-hydroxy-3-oxo-17α-androstane-21,17-carbolactone, that is not isolated. To this oily mixture a mixture of water/organic base is directly added. Bases that can be used are pyridine, triethylamine, a collidine (any one of the possible trimethylpyridines), 1,8-diazabicyclo[5.4.0]undec-7-ene and 1,5-diazabicyclo[4.3.0]non-5-ene and derivatives thereof. The preferred base is pyridine. Pyridine is a reagent/solvent commonly employed in industry; it has a low cost, is stable over time and does not pose particular problems of application, and the water/pyridine mixture can be recovered at the end of the reaction by means of simple distillation and re-used in successive production cycles.
The volume ratio of water to the base can vary between about 5:1 and 1:4. In the case of pyridine, for example, it is possible to use the azeotropic mixture, which presents a water/pyridine volume ratio of 0.74. The inventors have observed that it is not necessary for the water used to be purified or distilled.
The reaction temperature can vary generally between 45 and 90° C., depending on the base used and on its volume ratio to water: the water/base mixtures prepared with the aforementioned bases have boiling temperatures that vary depending on the actual composition, and the maximum temperature of the reaction must be below the boiling temperature of the specific water/base mixture used.
The reaction is completed in a time period comprised between 1 and 20 hours, and does not need to be carried out in an inert atmosphere.
The crude drospirenone produced with the described process has an HPLC purity grade above 98.5%; further purifications of the product, aimed at obtaining a pharmaceutical grade thereof, can be achieved according to the common techniques known to industry experts, such as recrystallization.
Thanks to the use of a mixture of reagents that present no danger, safety and flammability problems, the reaction can be carried out in a simple plant, created without special safety restrictions, and which does not require specific heating or cooling systems. On completion of the reaction there are no residues containing heavy metals or other hazardous waste.
The invention will be further illustrated by means of the following examples.
In the examples, the indicated amounts of drospirenone obtained are measured by means of quantitative analyses carried out on the raw product (HPLC titration vs. reference sample; HPLC instrument Agilent model 1200); the yields are calculated on the basis of these absolute amounts.
EXAMPLE 1
28 g of 17α-(3-hydroxypropyl)-6β,7β;15β,16β-dimethylene-5β-androstane-3β,5,17β-triol are dissolved in the reaction vessel at 35° C. in 56 ml of tetrahydrofuran. 712 ml of chloromethane and 420 ml of 10% by weight aqueous solution of sodium bicarbonate are added and the biphasic mixture thus obtained is cooled under agitation at 10° C.
The TEMPO catalyst and calcium hypochlorite as oxidising agent are added in successive doses under agitation, leaving the mixture to react for 1 hour after each addition and monitoring the degree of progress of the reaction with thin layer chromatography (TLC) at the end of each period. In particular, 700 mg of TEMPO are added in the first dosage and 11.2 g of calcium hypochlorite are added a few minutes later.
It is agitated while bringing the temperature to 28-30° C. After 1 hr the TLC check shows a partial reaction. While maintaining agitation at a temperature of 28-30° C., a second dosage of 500 mg of TEMPO takes place and 11.2 g of calcium hypochlorite are added a few minutes later. The reaction is left to progress and after one hour an incomplete reaction is still observed with TLC. While continuing to maintain agitation at 28-30° C., a third dosage of 140 mg of TEMPO takes place and 4.2 g of calcium hypochlorite are added a few minutes later. One hour later the TLC check confirms that the reaction is complete, the starting triol not being detectable.
110 ml of dichloromethane are added to the reaction mixture that is filtered with diatomaceous earth. The filter is washed with further 100 ml of dichloromethane. The aqueous and organic phases are separated and the latter is successively washed with 520 ml of 2% by weight aqueous NaHSO 4 solution and with 520 ml of 4% by weight aqueous sodium chloride solution. The pH of the final aqueous phase is 7. The organic phase is agitated for a few minutes with 1.2 g of decolorizing charcoal and with 1.2 g or diatomaceous earth. The suspension is filtered, washing the filter with 60 ml of dichloromethane.
The organic phase is distilled until an oily, semi-solid residue is obtained that is not removed from the reaction vessel. 280 ml of water and 280 ml of pyridine are added to the same vessel. The mixture is brought, under agitation, to a temperature of 45-50° C. for 16 hours. After this period, a TLC check confirms that the reaction is complete; a homogeneous spot is observed with Rf corresponding to the DRSP (controlled with a spot of pure product in the TLC itself).
310 ml of pyridine-water mixture are distilled under reduced pressure (T of the distillation vapours=24-25° C.). 460 ml of water are added and the distillation then takes place, removing further 50 ml of solvent. 75 ml of isopropyl acetate are added and the system is agitated while cooling with a water-ice bath, observing in the distillation flask the formation of a solid that is filtered and dried under reduced pressure. 12.3 g of drospirenone are obtained. A further 6.1 g of drospirenone are obtained from concentration of the organic phase, with total yield of the recovered product, relating to the starting triol, equal to 70%.
EXAMPLE 2
The oxidation reaction of Example 1 is repeated, using 1 g of the starting triol; reagents and solvents are used in the same proportions, relative to the triol, as in Example 1.
At the end of the oxidation phase 10 ml of water and 20 ml of pyridine are added to the same vessel and the mixture is heated under agitation to a temperature comprised between 58 and 62° C. for 7 hours. At the end of this period, the TLC check confirms that the reaction is complete (homogeneous spot with Rf corresponding to drospirenone).
The reaction mixture is distilled under reduced pressure thus obtaining 1023 mg of crude product which, titrated by HPLC, contain 685 mg of drospirenone, with a reaction yield, calculated with respect to the initial triol, of 73%.
EXAMPLE 3
The procedure of Example 2 is repeated, in this case adding 10 ml of water and 15 ml of pyridine at the end of the oxidation reaction. After the TLC check, which confirms that the reaction is complete (homogeneous spot with Rf corresponding to drospirenone), the reaction mixture is distilled under reduced pressure, thus obtaining 1027 mg of crude product which, titrated by HPLC, contain 684 mg of drospirenone, with a reaction yield, calculated with respect to the initial triol, of 73%.
EXAMPLE 4
The procedure of Example 2 is repeated, in this case adding 10 ml of water and 10 ml of pyridine at the end of the oxidation reaction. After the TLC check, which confirms that the reaction is complete (homogeneous spot with Rf corresponding to drospirenone), the reaction mixture is distilled under reduced pressure, thus obtaining 1,005 mg of crude product which, titrated by HPLC, contain 679 mg of drospirenone, with a reaction yield, calculated with respect to the initial triol, of 72%.
EXAMPLE 5
The procedure of Example 2 is repeated, in this case adding 10 ml of water and 5 ml of pyridine at the end of the oxidation reaction. After the TLC check, which confirms that the reaction is complete (homogeneous spot with Rf corresponding to drospirenone), the reaction mixture is distilled under reduced pressure, thus obtaining 995 mg of crude product which, titrated by HPLC, contain 652 mg of drospirenone, with a reaction yield, calculated with respect to the initial triol, of 69%.
EXAMPLE 6
The procedure of Example 2 is repeated, in this case adding 10 ml of water and 2.5 ml of pyridine at the end of the oxidation reaction, while continuing to heat the mixture, in this case for 15 hours. After the TLC check, which confirms that the reaction is complete (homogeneous spot with Rf corresponding to drospirenone), the reaction mixture is distilled under reduced pressure, thus obtaining 1,012 mg of crude product which, titrated by HPLC, contain 579 mg of drospirenone, with a reaction yield, calculated with respect to the initial triol, of 62%.
EXAMPLE 7
Comparative
The procedure of Example 2 is repeated, in this case adding 10 ml of water and 10 ml of pyridine at the end of the oxidation reaction, while in this case continuing to heat the mixture to a temperature comprised between 38 and 42° C. for 20 hours, that is, below the lower limit of the range of temperatures of the invention for the dehydration reaction. After the TLC check, which confirms that the reaction is complete (homogeneous spot with Rf corresponding to drospirenone), the reaction mixture is distilled under reduced pressure, thus obtaining 895 mg of crude product which, titrated by HPLC, contain 329 mg of drospirenone with a reaction yield, calculated with respect to the initial triol, of 35%.
EXAMPLE 8
The procedure of Example 7 is repeated, heating in this case the mixture to a temperature comprised between 78 and 82° C. for 15 hours. After the TLC check, which confirms that the reaction is complete (homogeneous spot with Rf corresponding to drospirenone), the reaction mixture is distilled under reduced pressure, thus obtaining 1,002 mg of crude product which, titrated by HPLC, contain 652 mg of drospirenone with a reaction yield, calculated with respect to the initial triol, of 69%.
EXAMPLE 9
Comparative
The oxidation reaction of Example 2 is repeated.
On completion, 20 ml of pyridine are added to the oxidation product (without water). The mixture is heated under agitation for 18 hours at a temperature comprised between 48 and 52° C.
At the TLC check, the reaction is largely incomplete: the TLC shows two main spots, the principal one corresponding to the initial triol and the secondary spot to drospirenone. The solvent is recovered while recovering 1027 mg of residue that presents the same TLC profile as the previous check. Evaluations of yield are not carried out on the product.
EXAMPLE 10
Comparative
The oxidation reaction of Example 1 is repeated, using 500 mg of the initial triol; reagents and solvents are used in the same proportions, relative to the triol, as in Example 1.
At the end of the oxidation phase, 5 ml of ethanol, and 50 mg of sodium methylate (CH 3 ONa) are added to the reaction flask and the mixture is kept under agitation for 1 hr at a temperature comprised between 38 and 42° C. At the end of this period, the TLC check confirms that the reaction is complete (homogeneous spot with Rf corresponding to drospirenone). The reaction solution pH is corrected to ≈6 with acetic acid then the solvent is distilled under reduced pressure.
The residue is re-dissolved with 5 ml of water and 5 ml of dichloromethane. The organic phase is dry concentrated under reduced pressure.
The product obtained (395 mg), re-checked by TLC, shows more than one spot. The content in drospirenone in the sample, determined by HPLC analysis with a reference sample, is equal to 36% by weight.
The reaction yield, calculated with respect to the initial triol, is of 30%.
EXAMPLE 11
The oxidation reaction of Example 1 is repeated, preparing an initial mixture with 28 g of triol dissolved in 60 ml of tetrahydrofuran at 35° C., to which 710 ml of dichloromethane and 420 ml of an aqueous solution of sodium bicarbonate at 10% are added, thus obtaining a biphasic mixture which is cooled to 10° C. under agitation.
The addition of calcium hypochlorite and TEMPO takes place in three successive dosages, as described in Example 1, under agitation and while maintaining the reacting mixture at a temperature of 28-30° C.; 700 mg of TEMPO are added in the first dosage and 11.2 g of calcium hypochlorite are added a few minutes later (TLC check result after 1 hour: partial reaction); 510 mg of TEMPO are added in the second dosage and 11.4 g of calcium chloride are added a few minutes later (TLC check result after 1 hour: partial reaction); and 130 mg of TEMPO are added in the third dosage and 4.0 g of calcium hypochlorite are added a few minutes later. One hour after this last dosage of oxidising agent and catalyst, the reaction is complete, the starting triol not being detected at the TLC check.
120 ml of dichloromethane are added to the reaction mixture that is filtered with diatomaceous earth. The filter is washed with further 100 ml of dichloromethane.
The phases are separated and the organic phase is successively washed with 520 ml of 2% by weight aqueous NaHSO 4 solution and then with 520 ml of 4% by weight aqueous sodium chloride solution. The pH of the final aqueous phase is 7.
The organic phase is agitated for a few minutes with 1.2 g of decolorizing charcoal and with 1.5 g or diatomaceous earth. The suspension is filtered, washing the filter with 60 ml of dichloromethane.
The organic phase is roughly distilled until an oily, semi-solid residue is obtained. 280 ml of water and 140 ml of pyridine are added to the distillation flask. The mixture is heated under agitation to a temperature comprised between 58 and 62° C. for 20 hours. At the end of this period, a TLC check confirms that the reaction is complete: a homogeneous spot with Rf corresponding to drospirenone is observed. 200 ml of pyridine/water mixture are distilled under reduced pressure (temperature of the distillation vapours=24-25° C.).
200 ml of water are added, the system is cooled to 20-25° C. and extracted with 300 ml of dichloromethane. After washing with water, the organic phase is filtered and treated with decolorizing charcoal (1.2 g), diatomaceous earth (1.2 g), sodium sulphate (4.8 g) and refiltered The solvent is distilled, eliminating the residual pyridine by means of distillation with methyl isobutyl ketone.
The residue, crystallized by isopropyl acetate, provides 14.5 g of drospirenone (constant weight after drying at 50° C. and reduced pressure). A further 4.36 g of drospirenone are recovered by further crystallization from the mother liquors. The crystallization residue, checked in TLC, shows the presence of drospirenone. Following chromatography, a further 1.4 g of drospirenone are recovered, for a total recovered product yield, relating to the initial triol, of 78%.
EXAMPLE 12
The oxidation reaction of Example 1 is repeated, using 500 mg of the initial triol; reagents and solvents are used in the same proportions, relative to the triol, as in Example 1.
At the end of the oxidation phase, 5 ml of water and 15 ml of pyridine are added to the reaction flask and the mixture is heated under agitation at a temperature comprised between 48 and 52° C. for 15 hours. At the end of this period, the TLC check confirms that the reaction is complete, showing a homogeneous spot with Rf corresponding to drospirenone.
The reaction mixture is distilled under reduced pressure thus obtaining 502 mg of crude product. The content in drospirenone in the sample, always determined by HPLC analysis against the reference sample, turns out of 66% (by weight) for a total amount of 331 mg of DRSP, corresponding to a reaction yield, relating to the initial triol, of 71%.
EXAMPLE 13
Comparative
The oxidation reaction of Example 12 is repeated.
At the end of the oxidation phase, 20 ml of water are added to the reaction flask; a suspension is formed. The mixture is heated for 16 hours under agitation at a temperature comprised between 48 and 52° C.
After this period, the TLC check reveals that the reaction is highly incomplete: the TLC shows two spots, with the secondary, barely visible spot, corresponding to drospirenone (traces).
EXAMPLE 14
Comparative
The oxidation reaction of Example 2 is repeated; reagents and solvents are used in the same proportions, relative to the triol, as in Example 1.
At the end of the oxidation phase, and after distillation, 100 mg of KOH are added to the reaction vessel.
The mixture is heated under agitation to a temperature comprised between 58 and 62° C. for 16 hours. The formation of drospirenone is not observed at the TLC check. In confirmation of the TLC result, the reaction mixture is analysed by HPLC, giving as result an HPLC titre in drospirenone equal to 1.0%.
EXAMPLE 15
Comparative
The oxidation reaction of Example 15 is repeated.
At the end of the oxidation phase, and after distillation, 10 ml of 1.8-diazabicyclo[5.4.0]undec-7-ene (DBU) are added to the reaction vessel.
The mixture is heated under agitation to a temperature comprised between 58 and 62° C. for 16 hours. A partial reaction is observed at TLC check, with principal spot not corresponding to drospirenone and with Rf=0. The organic solution is titrated with HPLC thus obtaining a molar reaction yield of 34%.
EXAMPLE 16
Comparative
The oxidation reaction of Example 15 is repeated.
At the end of the oxidation phase, and after distillation, 10 ml of triethylamine (TEA) are added to the reaction vessel.
The mixture is heated under agitation to a temperature comprised between 58 and 62° C. for 16 hours. The formation of drospirenone is not observed at the TLC check. In confirmation of the TLC result, the reaction mixture is analysed by HPLC, giving as result an HPLC titre in drospirenone equal to 2.1%.
Comment to the Results
The results of the tests are summarized in the table below, which reports, in the columns from left to right: the number of the Example (the asterisk indicates a comparative example), the millimoles of starting triol, the volume/volume ratio of water to the base (when no ratio is indicated, in comparative examples, it is given the indication of the base used, or water only in comparative example 13), the temperature and time conditions of the dehydration reaction, the millimoles of drospirenone obtained, and the yield of drospirenone obtained (as percent relative to the moles of starting triol).
Dehydration
conditions
DRSP
mmol
H 2 O/base ratio
temperature
time
mmol
yield
Ex.
triol
(v/v)
(° C.)
(hours)
DRSP
(%)
1
71.69
1:1
45-50
16
50.20
70
2
2.56
1:2
58-62
7
1.87
73
3
2.56
1:1.5
58-62
7
1.87
73
4
2.56
1:1
58-62
7
1.85
72
5
2.56
2:1
58-62
7
1.78
69
6
2.56
4:1
58-62
15
1.58
62
7*
2.56
1:1
38-42
20
0.90
35
8
2.56
1:1
78-82
15
1.78
69
9*
2.56
pyridine only
48-52
18
n.a.
n.a.
10*
1.28
CH 3 ONa in
38-42
1
n.a.
30
EtOH
11
71.69
2:1
58-62
20
55.28
77
12
1.28
1:3
48-52
15
0.90
71
13*
1.28
water only
48-52
16
n.a.
traces
14*
2.56
KOH
58-62
16
n.a.
1
15*
2.56
DBU
58-62
16
n.a.
34
16*
2.56
TEA
58-62
16
n.a.
2
As can be seen by the comparison of results between comparative example 7 on one hand, and examples 1, 4 and 8 on the other hand, simply reducing the temperature a few degrees below 45° C., the lower limit of the range of the invention for the dehydration reaction, leads to a dramatic reduction in yield of DRSP, that goes down to about one half compared to the figures obtained with the process according to the invention.
Similarly, the examples show poor or negligible DRSP yields if another condition of the invention, namely the use of a mixture of an organic base with water as dehydrating agent, is not adopted. As can be observed from examples 9, 10, and 14-16, the use of bases, even strong ones (such as CH 3 ONa in comparative example 10) is not efficient if these are not used in mixture with water.
Finally, comparative example 13 confirms that heating alone (treatment with water alone at about 50° C. for 16 hours) is not effective to obtain dehydration of 5β-OH-DRSP. | It is described of a process for the preparation of drospirenone, the compound of formula 1 shown below, a synthetic steroid with progestogenic, antimineralocorticoid and antiandrogenic activity, useful for preparing pharmaceutical compositions having contraceptive action, starting from 17α-(3-hydroxypropyl)-6β,7β;15β,16β-dimethylene-5β-androstane-3β,5,17β-triol. | 2 |
CROSS REFERENCE
This application claims the benefit of U.S. Provisional Patent Application Ser. No. 61/321,645 filed on Apr. 7, 2010, the contents of which are incorporated herein by reference.
FIELD OF THE INVENTION
This invention relates to control assemblies for drive systems used in self-propelled vehicles and machines. The invention is particularly useful for controlling a pump/motor combination, transmission, or transaxle used in self-propelled vehicles and machines such as riding lawn mowers, snow-throwers, and lawn or garden tractors.
BACKGROUND OF THE INVENTION
Self-propelled vehicles and machines such as riding lawn mowers, snow-throwers, and lawn or garden tractors using variable speed drives are well known. Such variable speed drives, whether hydrostatic, toroidal, friction, or the like, will generally have a control shaft whose rotation, via manipulation of an operator control mechanism mechanically linked to the control shaft, regulates the variable speed drive's output. As an example, many zero-turn mowers employ a pair of pumps which independently transmit hydraulic fluid, and thus power, to a corresponding pair of hydraulic motors, each independently driving a separate axle and wheel combination to provide steering. The control mechanism utilized by an operator of the machine often employs a damper to prevent sudden acceleration or deceleration of the machine resulting from unintended manipulation of the control mechanism, for example, when the operator is jostled upon striking a bump, dip, or other obstacle in the machine's path. Dampers may be used between the operator control levers and the frame or body of the zero-turn mower, using mounting points on the mower's body or frame distant from the variable speed drive system. Dampers may also be connected directly to a control arm, the mechanical link between the control shaft of the pump and the operator control mechanism. Again, additional mounting points are necessary to effectuate the damping effect.
It would be advantageous for manufacturers of self-propelled vehicles and machines to eliminate bulky dampers and their associated mounting points, reducing manufacturing costs and assembly complexity, while retaining the functional benefits of the dampers.
SUMMARY OF THE INVENTION
This invention relates to an assembly useful for controlling a variable speed drive having a control shaft projecting from its housing. The reference to a variable speed drive as used herein will be understood to include, at a minimum, pumps, transmissions and transaxles, whether hydrostatic, toroidal, friction or the like. The control assembly comprises a control arm fixed on the control shaft to effect rotation thereof; a return to neutral mechanism disposed about the control shaft to bias the control shaft to a neutral position; and a rotary, viscous fluid damper integrated with the return to neutral mechanism, the damper having a rotor engaged to the control shaft and a stator fixed to the housing of the variable speed drive to moderate, or slow the rotational movement of the control shaft under the influence of inputs from the control arm and the return to neutral mechanism. The neutral arm of the return to neutral mechanism may be integrally formed with the external case of the rotary, viscous fluid damper, creating a compact control mechanism. The inclusion of the damper mechanism in the control assembly makes it unnecessary for a manufacturer to supply a separate dampening mechanism in the control linkage of a vehicle or machine employing such a variable speed drive. This invention also relates to a variable speed drive fitted with the control assembly.
A better understanding of the objects, advantages, features, properties and relationships of the invention will be obtained from the following detailed description and accompanying drawings which set forth illustrative embodiments that are indicative of the various ways in which the principles of the invention may be employed.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side elevation view of an exemplary transaxle incorporating the control assembly in accordance with one embodiment of the invention.
FIG. 2 is a cross-section of the transaxle of FIG. 1 taken along line 2 - 2 .
FIG. 3 is a partially exploded perspective view of the control assembly shown in FIG. 1 .
FIG. 4 is an exploded perspective view of the rotary damper subassembly shown in FIGS. 1 and 3 .
FIG. 5 is an exploded perspective view showing the reverse sides of elements of the rotary damper subassembly shown in FIG. 4 .
DETAILED DESCRIPTION OF THE INVENTION
The description that follows describes, illustrates and exemplifies one or more embodiments of the present invention in accordance with its principles. This description is not provided to limit the invention to the embodiments described herein, but rather to explain and teach the principles of the invention in order to enable one of ordinary skill in the art to understand these principles and, with that understanding, be able to apply them to practice not only the embodiments described herein, but also other embodiments that may come to mind in accordance with these principles. The scope of the present invention is intended to cover all such embodiments that may fall within the scope of the appended claim, either literally or under the doctrine of equivalents.
Turning now to the figures, wherein like reference numerals refer to like elements, an embodiment of a control assembly 30 of the present invention is depicted in FIGS. 1 and 2 as used in connection with a transaxle 10 , which may be substantially identical to that described in commonly owned U.S. Pat. No. 7,134,276, the disclosure of which is incorporated herein by reference. The details of transaxle 10 are not critical to this invention; this invention could also be used on other transaxle, transmission, or even pump designs and this disclosure should not be read as limited to use with a zero-turn transaxle such as transaxle 10 . The variable speed drive may comprise a hydrostatic or hydraulic pump in a housing or a mechanical mechanism such as a toroidal drive, so long as there is a control shaft to regulate the output of the variable speed drive and extending from the housing of the variable speed drive. The return to neutral design depicted herein is bi-directional in function and similar in many respects to that shown in commonly owned U.S. Pat. No. 7,313,915. The return to neutral design depicted herein is also similar to the bi-directional and uni-directional designs disclosed in commonly owned U.S. Pat. No. 6,782,797. It will be understood that the control assembly of the present invention may be used in connection with other return to neutral designs and that this invention is not so limited. For further details on the operation of transaxle 10 or the return to neutral feature, the reader is referred to the patents referenced above, which are incorporated by reference herein in their entirety.
The element of transaxle 10 upon which the control assembly 30 acts is a control shaft, in this instance, trunnion shaft 26 a which extends from main housing 12 . Though trunnion shaft 26 a is depicted in FIG. 2 as integral with movable swash plate 26 , it will be understood that the trunnion shaft may be a separable element from the swash plate. The general design of a hydrostatic transmission, such as transaxle 10 , is well known in the art and generally includes a variable displacement, axial piston pump 20 and a fixed displacement, axial piston motor (not shown), each carrying a plurality of reciprocating pistons which are placed in fluid communication through hydraulic porting located in a center section 22 . When swash plate 26 is rotated away from a neutral position, the rotation of pump 20 against moveable swash plate 26 creates an axial motion in the pump pistons that forces an operating oil through the hydraulic porting to the axial piston motor, displacing the motor pistons and causing rotation of the motor to drive an output shaft or axle. The flow of operating oil from pump 20 may be reversed by changing the direction of rotation of swash plate 26 away from the neutral position, thereby reversing the direction of rotation of the motor output shaft or axle. The axial piston pump 20 is driven by an input shaft 18 , which is generally powered by a prime mover (not shown) such as an internal combustion engine or electric motor. Side housing 14 is secured to main housing 12 by a plurality of fasteners 16 , forming a sump for the operating oil. In an alternate transaxle embodiment (not shown), wherein the trunnion shaft extends from the side housing, control assembly 30 may be disposed about the trunnion shaft adjacent the side housing.
In general terms, control assembly 30 consists of a rotary damper subassembly 40 , a control arm 28 , and a scissor arm style, return to neutral subassembly 32 . Rotary damper subassembly 40 has a backing plate 42 as part of its external case, wherein certain cooperative elements of the return to neutral subassembly are integrally formed therewith. Specifically, a neutral arm extension 42 a radially disposed from the trunnion shaft 26 a and a pair of openings 42 d . As shown in FIG. 3 , proper placement of control assembly 30 is assured by the mating of a centering ring 12 a formed on main housing 12 with the centering flange 42 b formed in the backing plate 42 of rotary damper subassembly 40 . Screw 70 and washer 72 retain the various elements of control assembly 30 on trunnion shaft 26 a , though other means known in the art may be used to connect such elements.
Control arm 28 is fixed to the end of trunnion shaft 26 a , preferably by providing control arm 28 , trunnion shaft 26 a and the center opening of a damper rotor 46 (as shown in FIG. 4 ) with complementary mating shapes, so that rotation of control arm 28 will also result in rotation of trunnion shaft 26 a and damper rotor 46 . Control arm 28 may be connected, via a driving link, to a lever or pedal (not shown) provided on the vehicle (not shown) whereby movement of the lever or pedal is translated to the speed adjusting mechanism 30 to cause the rotation of trunnion shaft 26 a and movement of swash plate 26 .
As shown in FIGS. 1 , 2 , and 3 , return to neutral subassembly 32 of control assembly 30 is of the scissors-arm style, comprising an inner scissors return arm 34 and an outer scissors return arm 36 rotatably disposed at the end of trunnion shaft 26 a . A biasing means such as spring 38 is linked to inner and outer scissors return arms 34 and 36 .
Control assembly 30 also functions to substantially establish the neutral position of trunnion shaft 26 a , i.e., the position of trunnion shaft 26 a where swash plate 26 does not cause flow of hydraulic fluid within the hydraulic circuit of a hydrostatic transmission such as that depicted. During the mating of control assembly 30 to transaxle 10 , trunnion shaft 26 a and the attached control arm 28 are rotated to the position that corresponds to the neutral position of swash plate 26 . The neutral arm extension 42 a of rotary damper backing plate 42 is rotated into radial alignment with a similar control arm extension 28 a integrally formed on control arm 28 to demarcate the neutral position. Neutral arm extension 42 a may be locked into this neutral position by means of a neutral set screw 60 and lockdown washer 62 combination, or the like, inserted through opening 42 d to mate with a boss on main housing 12 . Two openings 42 d are provided to permit the control assembly 30 to be rotated 180 degrees to allow for various mating orientations with external operating linkages. The configuration and operation of the return to neutral subassembly 32 , via the interaction of the contact surfaces 34 a and 36 a of the inner scissor return arm 34 and the outer scissor return arm 36 , respectively, with the neutral arm extension 42 a and control arm extension 28 a , is otherwise conventional as described in U.S. Pat. No. 7,313,915 and will not be recited herein.
Because control assemblies such as control assembly 30 comprise a plurality of components, it is advantageous to preassemble a portion of them in order to simplify assembly and reduce costs. Rotary damper subassembly 40 , shown in FIGS. 3 , 4 and 5 as part of control assembly 30 , serves to dampen the movement of trunnion shaft 26 a and, thus, make changes in the position of swash plate 26 less abrupt than they would otherwise be. This dampening substantially decreases unwanted and unintentional jarring movements of the trunnion shaft 26 a due to passage of a self-propelled vehicle or machine so equipped over rough terrain, thereby providing smoother control of the pump 20 and thus, smoother control of the associated motor output. This dampening also prevents sudden reversal of the motor and reduces bucking of the vehicle or machine, similarly reducing the risk of damage to the hydraulic equipment. Though the control assembly and its benefits are described in conjunction with a hydrostatic transaxle, the control assembly of the present invention will impart similar benefits to any variable speed drive having a control shaft extending from its housing.
Rotary damper subassembly 40 comprises a viscous fluid damper formed of damper backing plate 42 , o-ring seal 50 , damper stator 44 , damper rotor 46 , o-ring seals 52 and 54 , and damper cover 48 . On a first side, damper stator 44 has anti-rotation projections 44 b that mate with and project through openings 42 c on damper backing plate 42 to prevent rotation of damper stator 44 , and a seat 44 c for o-ring seal 50 . On a second side opposite the first side, damper stator 44 has concentric friction rings 44 a projecting therefrom and a seat 44 d for o-ring seal 54 . Concentric friction rings 44 a mesh with concentric friction rings 46 a of damper rotor 46 in an environment of viscous fluid to produce the dampening effect. Concentric friction rings 46 a of damper rotor 46 additionally have slots 46 b therein to allow passage of a viscous fluid therethough. Damper rotor 46 also has fluid openings 46 c in rotor face 46 d which allow passage of viscous fluid therethrough, serving to provide additional damping surface area and lubrication between rotor face 46 d and the inside face 48 a of damper cover 48 when damper rotor 46 rotates due to manipulation of control arm 28 . The viscous fluid that fills the void space in the rotary, viscous fluid damper can be a grease such as “PTFE-thickened damping grease” or a “Fluorocarbon Gel,” each available from Nye Lubricants, Fairhaven, Mass., USA. It will be apparent to one of ordinary skill that the viscosity of the viscous fluid can be varied to obtain the desired dampening effect from the rotary, viscous fluid damper. Damper cover 48 is secured to damper backing plate 42 , e.g. by friction fit of guide indentations or the like (not shown) on the rim of the cover, or by crimping features such as tabs and slots (not shown) to secure the parts of the rotary damper subassembly 40 .
Inner scissors return arm 34 and outer scissors return arm 36 may also be pre-assembled to form bi-directional scissors return subassembly 32 , as shown in FIG. 3 . The use of these separate subassemblies simplifies the assembly of the entire control assembly and the transaxle.
While specific embodiments have been described in detail, it will be appreciated by those skilled in the art that various modifications and alternatives to those details could be developed in light of the overall teachings of the disclosure. Accordingly, the particular arrangements disclosed are meant to be illustrative only and not limiting as to the scope of the invention which is to be given the full breadth of the appended claims and any equivalent thereof. | An integrated assembly useful for controlling a variable speed drive having a housing and a control shaft projecting therefrom. The control assembly consists of a control arm fixed on the control shaft to effect its rotation; a return to neutral mechanism disposed about the control shaft to bias the control shaft to a neutral position; and a rotary, viscous fluid damper integrated with the return to neutral mechanism, the damper having a rotor engaged to the control shaft and a stator fixed to the housing of the variable speed drive to moderate, or slow the rotational movement of the control shaft under the influence of inputs from the control arm and the return to neutral mechanism. The neutral arm of the return to neutral mechanism is integrally formed with the external case of the rotary, viscous fluid damper, creating a compact control mechanism. | 1 |
This application is a continuation of prior application No. PCT/AU02/00357, Mar. 25, 2002.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to an apparatus and method for making markings on ground surfaces such as turf playing fields and fairways. The invention has particular although not exclusive application where there is a need to automatically produce signs, such as logos or advertisements for example, on large ground surfaces whether even, sloped or undulating.
2. Discussion of the Background Art
A variety of arrangements for marking turf, such as the turf of playing fields, are known in the prior art. The simplest turf marking involves the application of straight lines to demarcate playing field boundaries. Commercially available line marking machines are used to facilitate such marking. Such machines may include a line of sight guide to aid the operator in producing a straight line between two reference points. Line marking machines are not suitable for producing complex signs or logos on turf.
Over the last two decades there has been a trend to mark playing fields with signs such as corporate logos or advertisements. High profile sporting events attract large crowds and television coverage so that turf advertisements are effective as such events are viewed by a large audience.
One way in which signs have traditionally been produced on turf has been with the help of stencils having apertures through which paint is sprayed or otherwise applied. The production and application of stencils for creating complex and large turf markings is time consuming and prone to error.
The surface of grounds such as sporting fields typically include variations in surface level, such as for drainage purposes. These variations can vary from tens of centimetres and upwards across conventional sporting fields. Large variations or undulations can cause distortion of logos and possibly affect viewing by spectators. On a golf course there are deliberate variations and undulations in ground surfaces, which exacerbate problems with application and viewing of ground markings. Hitherto it has not been widely known to automatically apply complex markings to ground surfaces, especially to turf which is non-planar, undulating or uneven, since neither of the previously discussed approaches to the generation of turf markings are particularly suited to application on a non-planar or sloping surface.
SUMMARY OF THE INVENTION
Object of the Invention
It is an object of the present invention to provide methods and apparatus that are an improvement over presently available methods and apparatus for marking ground surfaces with designs such as corporate logos.
It is an object of certain embodiments of the invention to provide methods and apparatus for automatically and efficiently marking level/even or undulating/uneven turf with complex patterns or logos.
Disclosure of the Invention
According to a first aspect of the invention there is provided an automatic ground marking apparatus including:
a carriage responsive to carriage control signals for traversing the ground, the carriage having a controllable steering and drive system and a controllable marking system;
a position determining system arranged to determine the position of the carriage; and
a processor responsive to the position determining system and operatively executing a software product for generating said carriage control signals wherein the controllable steering and drive system respond to said carriage control signals to cause the carriage to traverse the ground and mark out a predetermined sign on the ground.
In the present specification, the term “position” includes position of an object in three dimensional (3D) space, including the latitude, longitude and height of the object relative to a predetermined point of reference.
If required, the carriage control signals are transmitted to the carriage from a remote processor, which processor is associated with points defining the predetermined sign.
Preferably the position determining system comprises a laser based electronic distance measuring system including a base station and a reflector.
In one embodiment the base station is mounted to the carriage. In this embodiment the processor is also mounted to the carriage and connected to receive position data from the base station.
In an alternative embodiment the base station is fixed to the ground and the reflector is mounted to the carriage.
In that event the processor is connected to receive position data from the base station, the marking system further including a radio link to relay carriage control signals to the carriage.
The controllable steering and drive system may incorporate an on-board compass with further processing apparatus responsive to the compass and arranged to determine an actual bearing of the carriage.
Preferably the further processing apparatus compares the actual bearing with a desired bearing encoded in the guidance signals transmitted.
The desired bearing is typically generated by the carriage guidance system.
As an alternative to the laser based electronic distance measuring system, the carriage guidance system may instead include a GPS receiver.
Preferably the controllable marking system includes a reservoir for a marking medium, such as paint, and a dispensing nozzle. A controllable valve may interconnect the reservoir and dispensing nozzle.
The controllable steering and drive system may include a number of independently controllable drive units each coupled to a corresponding wheel of the carriage.
The carriage may further include a feedback sensor arranged to provide a feedback signal to the processor.
The feedback sensor may be a shaft encoder, an inclinometer or a compass.
Where the processor is located external of the carriage, a convenient way in which the feedback signal may be relayed to the processor is by means of a radio link.
According to a further aspect of the present invention there is provided a computer software product stored on a computer readable memory and executable by a processor for causing a carriage including a controllable steering and drive system and a controllable marking system to mark out a sign the software product including:
carriage position instructions for reading a carriage position from a data stream generated by a position sensing device;
sign point instructions for reading a file of points defining a predetermined sign;
command instructions for generating commands to cause a carriage to traverse the ground surface and dispense paint on the surface in order to mark out said sign.
In another aspect of the present invention there is provided a method for surveying an area by means of an automated carriage arranged to move over a predetermined path, the method comprising the steps of:
initiating movement of the carriage over the path;
monitoring the position of the carriage; and
recording position coordinates of the carriage in a computer file.
Preferably the step of monitoring the position of the carriage is achieved by means of an EDM system at a remote site, wherein a reflective portion of said system is mounted on the carriage and wherein the base station of the EDM system is at least part of the remote site. Alternatively, the EDM system may be on-board the carriage and arranged for interaction with remote reflectors.
BRIEF DETAILS OF THE DRAWINGS
In order that this invention may be readily understood and put into practical effect, reference will be made to the accompanying drawings wherein:
FIG. 1 depicts an automated turf-marking carriage according to one embodiment of the present invention;
FIG. 2 is a top plan view of the layout of the carriage of FIG. 1 with top cover removed;
FIG. 3 is a rear elevational view of the carriage of FIG. 2 ;
FIG. 4 is a flow chart of the steps implemented by a software product used in an embodiment of the present invention;
FIG. 5 is a flow chart showing the flow of data through the system of FIG. 1 ;
FIG. 6 depicts an automated turf-marking carriage according to a further embodiment of the present invention; and
FIG. 7 depicts an undulating turfed surface upon which a sign has been marked.
DESCRIPTION OF PREFERRED EMBODIMENTS
A preferred embodiment of an automatic turf marking system of the invention will be described in overview with reference to FIG. 1 . A manoeuvrable paint dispensing carriage 1 for traversing the ground 5 includes a reflective tracking prism 2 . A cover 3 covers the internal components of the carriage. An electronic distance measuring (EDM) base station 6 tracks the location of the carriage 1 by reflecting a laser beam 4 off the tracking prism. The base station 6 and prism 2 may be obtained as components of an AP-I1A auto-tracking electronic distance measuring system available from Topcon America Corporation of 37 West Century Road, Paramus, N.J. 07652, USA.
A lap-top computer 8 is coupled to a digital position data port on the base station 6 . As will be explained, the computer 8 includes a processor that executes a software product that compares position data from the base station with a pre-stored data file. The data file contains coordinate points defining a desired sign or logo to be applied to the turf. The software product may be configured to cause the computer 8 to display the desired logo on a display screen 10 . Under control of the software product, the processor generates a series of steering and paint dispensing instructions that are output to a radio transmitter 11 . The radio transmitter 11 transmits corresponding radio control signals to the carriage 1 for reception by an antenna 16 . The carriage receives the radio control signals and moves and releases paint in accordance with the control signals in order to mark out turf logo 14 .
It is not necessary for the entire turf logo to be marked out by carriage 1 . For example the software program may be configured so that the carriage marks out a number of points sufficient for a manual operator to complete the turf logo by hand. In the presently described embodiment, the EDM base station 6 , processor (in the form of the lap-top computer 8 ) and transmitter form a carriage guidance or position determining system. Although the EDM base station is coupled to the lap-top computer by a cable link in the drawings, it will be appreciated that the base station may be remotely controlled using radio link therebetween.
Referring now to FIG. 2 there is depicted a plan view of the module layout of carriage 1 with cover 3 removed. The carriage includes an antenna 16 coupled to a receiver 15 which in turn is coupled to a control module 20 . Also included are batteries 18 A, 18 B which provide power for the receiver 15 , the control module 20 , drive and steering modules 22 A– 22 D, a pump 27 and a solenoid actuated valve 26 .
The control module sends command signals to drive and steering modules 22 A– 22 D each of which are coupled to wheels 24 A– 24 D respectively by axle shafts 25 A– 25 D. As will be explained, shaft encoders may be employed to confirm that the steering and drive command signals are accurately carried out. The control module 20 also sends commands to solenoid actuated valve 26 in order to control the dispensing of paint through nozzle 29 onto turf 5 beneath the carriage 1 .
FIG. 3 is a rear view of the carriage of FIG. 2 viewed along arrow A, with battery 18 B removed. In another embodiment of the invention, the tracking prism 2 and dispenser nozzle 29 may be mounted on a gimbal structure whereby the prism may be maintained vertically above the nozzle, even when the carriage is required to traverse an inclined surface, such as that illustrated in FIG. 7 . This arrangement facilitates use of a taller mast 23 for carrying the tracking prism 2 , better suited to operation of the carriage 1 on sloping or undulating surfaces. If required, an inclinometer may be employed on the carriage. The inclinometer may be used either to automatically maintain the mast in a vertical orientation, or to transmit inclination data to the processor for real-time compensation of carriage inclination.
Referring now to FIG. 4 , there is depicted a flow chart of a process 30 coded into the software product executed by the processor of computer 8 in FIG. 1 . The software product contains instructions to implement each of the steps of FIG. 4 of the procedure that will now be described. It will be realised that the actual coding of the instructions is straightforward for persons skilled in this field, once the functionality of the software product is explained.
At step 32 the communication ports used by computer 8 to communicate with base station 6 and radio transmitter 11 are opened and tested.
At step 34 a pre-stored “map” file 9 (see FIG. 5 ) containing point coordinates defining the logo to be demarcated by carriage 1 is opened.
At step 36 a command to start the carriage moving forward is generated. The command is sent to transmitter 11 which in turn converts it to a radio frequency control signal that is transmitted to carriage 1 . The carriage receives the signal by means of antenna 16 , generates a corresponding baseband signal by means of receiver 15 and passes the baseband signal to control electronics module 20 . The control module generates corresponding commands that are sent to drive modules 22 A– 22 D in order to start the carriage moving forwards.
At step 38 the computer reads the next point from the map file and sets it to be the current point for processing. At step 40 the computer reads carriage position data from base station 6 . At step 44 the computer compares the data read at step 38 with the data read at step 40 . If the two points are not within a small distance of each other then the computer decides that the carriage is not at the point dictated by the map coordinate. Consequently, at step 48 the direction vector from the carriage to the desired map coordinate is calculated.
At step 52 the velocity vector of the carriage is calculated. At step 54 the difference between the direction vector and the velocity vector is determined in order to generate a turn command to turn the carriage so that it heads towards the map point. Control then diverts to step 40 and steps 40 to 54 are repeated until it is determined at decision point 44 that the carriage and the current map point are sufficiently close enough for it to be said that the carriage is at the current map point. If they are sufficiently close control diverts to step 46 .
At step 46 a mark command is generated causing a paint drop to be dispensed through nozzle 29 .
At decision point 42 the computer checks if the current point of the map file is the last point in the file. In the event that it is the last point then the procedure ends at step 50 . Alternatively, control passes back to step 38 and the previous procedure is repeated until all the points of the map file have been processed.
The flow chart of FIG. 4 shows the architecture, functionality, and operation of a possible implementation of the software product. In this regard, each block represents a module, segment, or portion of code, which comprises one or more executable instructions for implementing the specified logical functions). It should also be noted that in some alternative implementations, the functions noted in the blocks may occur out of the order noted in FIG. 4 . For example, two blocks shown in succession in FIG. 4 may in fact be executed substantially concurrently or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved.
With reference to FIG. 5 there is shown a block diagram of many of the components of the previously described system showing the flow of information enabling positioning of the carriage and dispensing of paint as previously described.
Apart from turf marking, the carriage 1 may also be used as a surveying tool in which mode it is run back and forth over a surface to be surveyed. The procedure is suitably as follows:
Initially a path is defined for the carriage to follow. The path may be defined in the same way as setting a path for marking. Normally the path will consist of parallel evenly spaced lines covering the surface in question. The carriage is then set up and commanded to follow the path. Each time the EDM equipment sends distance data to the computer it will also send the level or height of the carriage (Z coordinate) data. These levels or heights are stored in a file along with the corresponding latitude (X coordinate) and longitude (Y coordinate) position data.
The result is a data file defining a grid or points covering the area of interest that may be up-loaded to a computer-aided design (CAD) package for use in creating a digital terrain model (DTM). It will be appreciated that this survey procedure may be conveniently employed to create a DTM for the region of a surface desired to be marked.
Although not essential to operation, feedback sensors such as shaft encoders, a compass and/or an inclinometer may be included on the carriage 1 . Data from the feed back sensors may be transmitted back to computer 8 by means of an additional radio frequency (RF) link. The software program may contain instructions to process the received feedback data in order to modify the control signals transmitted thereby implementing a feedback control loop in order to minimise divergence of the carriage's path from the map coordinates.
Where an on-board computer is incorporated, the carriage guidance system may be arranged to transmit a desired direction bearing to the carriage. A processor on the carriage calculates the carriage's actual bearing as sensed by the compass and compares it to the desired bearing in order to generate commands to steer the carriage along the desired bearing. The carriage guidance system also sends the carriage signals to control speed and to dispense paint. Accordingly in this embodiment two separate computer programs work together.
While the invention has been described as making use of an electronic distance measuring apparatus in the form of a laser base station, it is possible to use other apparatus for determining the position of the carriage. For example, a global positioning system (GPS) receiver might be used, together with differential correction as required. However, GPS data is typically limited to 20 mm accuracy; whereas data derived from an EDM system as explained herein, typically achieves a minimum of 10 mm accuracy and tighter tolerances are usually achieved than is the case with GPS. Additionally, GPS may not be used indoors or in any area where the view of the sky is limited, since direct line of sight to a minimum of four GPS satellites is required for GPS to operate satisfactorily. This is a serious limitation in that it would prevent the turf marking carriage operating inside large sporting stadiums.
Accordingly, while the invention may make use of a GPS receiver in order to monitor the location of the carriage it is preferred that EDM technology of the type described herein is used.
A variation of the embodiment of FIG. 1 will be explained with reference to FIG. 6 . In FIG. 6 the EDM base station 6 has been mounted on carriage 1 whereas prism 2 has been fixed in the turf at a predetermined reference position. In this embodiment computer 8 is incorporated inside carriage 1 . The software program executed by the computer is very similar to that explained with reference to FIG. 4 except that it includes instructions to transform the position coordinate data to take into account the transposition of the base station and reflective prism 2 . A control panel 7 for entering data into the computer is mounted on cover 3 and is accessible to an operator. In this further embodiment the radio transmitter 11 and radio receiver 14 and antenna 16 are unnecessary, and so are not present. Accordingly, if the further embodiment is employed variations in the height or attitude of the EDM stations must be compensated out. It will be appreciated that use of the marking apparatus on substantially flat ground will obviate the requirement for height data.
In FIG. 7 there is shown a corporate logo “STONEWOLF” 62 applied to the sloping surface of turf 64 in the vicinity of a green 66 on a golf course 60 . It is anticipated that points providing an outline of the logo 62 may be automatically produced by a ground marking apparatus according to embodiment of the invention, allowing the negative image of the lettering to be in-filled by hand.
The automatic marking system of the invention allows the creation of logos which take environmental factors into account, including the undulations in the surface to receive the markings and the desired viewing positions for both audiences in attendance and television viewers. Ground slope angles can vary by up to 30%, such as in the case of golf course contours. In such circumstances, prior art methods do not provide a satisfactory result or are otherwise costly, time consuming and laborious.
It will of course be realised that the above description of marking turfed ground surfaces, such as sports fields, has been given only by way of illustrative example of the invention. All such modifications and variations thereto, as would be apparent to persons skilled in the art such as marking the surface of a car-park or roadway, are deemed to fall within the broad scope and ambit of the invention as is described herein and set out in the accompanying claims. | An automatic ground marking apparatus including a carriage ( 1 ) responsive to carriage control signals for traversing the ground ( 5 ), the carriage having a controllable steering and drive system, a controllable marking system and a position determining system ( 6 ) arranged to determine the position of the carriage. The ground marking apparatus further includes a processor ( 8 ) responsive to the position determining system and operatively executing a software product for generating the carriage control signals to cause the carriage ( 1 ) to mark out a predetermined sign ( 14 ) on the ground. The position determining system ( 6 ) suitably employs a laser beam ( 4 ) and reflective tracking prism ( 2 ), and the predetermined sign may be defined by data points stored in a file ( 9 ) accessed by the processor ( 8 ) (FIG. 1 ). | 0 |
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims the priority benefit of U.S. Provisional Patent Application Ser. No. 60/681,730 filed May 17, 2005.
BACKGROUND OF THE INVENTION
[0002] 1. Field of Invention
[0003] This invention relates to mowing machines, and more specifically, to a lawn mower that can selectively function as a bagging mower, a mulching mower and a discharge mower.
[0004] 2. Description of Related Art
[0005] Lawn mowers for cutting grass, weeds and leaves with a rotating cutting blade housed in a downward-opening mower deck are well known in the art. Generally, lawn mowers are classified in one of three classes, specifically: (1) bagging mowers that collect the grass cut by the cutting blade in a grass receptacle such as a hopper or bag; (2) side-discharge mowers that discharge the cut grass through an opening in the side of the mower deck in order to leave the grass clippings on the lawn; and (3) mulching mowers that that chop the grass clippings more finely within the cutting chamber formed by the mower deck and discharge the clippings downward of the deck.
[0006] Bagging-type lawn mowers collect grass clippings in the grass receptacle in order to remove all of the clippings from the lawn, thereby providing a professional quality appearance. However, the grass clippings collected in the grass receptacle must be carried to and dumped at a disposal site. The side-discharge and mulching-mode lawn mowers eliminate the need for dumping the grass clippings by returning grass clippings to the lawn. Mulching mowers chop the grass clippings into finer pieces so that they decompose more rapidly and give the lawn a good finished quality. However, if the grass is exceptionally tall or thick, mulching mowers tend to bog down with the excess grass clippings, leaving unsightly clumps and causing the mower to frequently stall. In such situations, discharging the grass clippings through a discharge chute in the mower deck as found on a side-discharge mower is the preferred option. It is commonly the case that a lawn caretaker may desire to use each of these different modes at different times, even on the same plot of grass.
[0007] In recent years, lawn mowers have been developed that can be selectively configured to operate in more than just a single mode of operation, e.g., the mower may be configured to operate as a mulching mower and a bagging mower, or even as a mulching mower, a side-discharge mower and a bagging mower. It is, however, inconvenient to reconfigure these lawn mowers between the different operational modes. Converting the lawn mower to a different operational mode typically involves the manual installation and/or removal of parts to the lawn mower requiring time consuming work. For example, mulching operations typically require the installation of a discharge cover or plug which a user must install in the discharge opening of the mower deck. If the user wants to switch back to the bagging mode of operation, the user must remove the mulch plug and reinstall the grass-collecting hopper. Tools are typically required to install or remove the mulching plug. The awkward, inconvenient and relatively time consuming process of installing and uninstalling the discharge plug also requires the installer to reach into the discharge opening with his/her hand, which can be difficult and messy. Additionally, the components not being used in the selected mode of operation, such as the mulch plug or the grass collection receptacle, must be stored separate from the lawn mower. Often, these parts become lost or misplaced or are otherwise not readily available when needed.
[0008] Therefore, there is a need for an improved lawn mower that can be easily reconfigured between a bagging mode, a mulching mode and a discharge mode by simple operation.
SUMMARY OF THE INVENTION
[0009] One aspect of the invention is a multi-use lawn mower that can be configured to operate in either a mulching mode, a discharge mode, or a bagging mode of operation, wherein the selection of the mode of operation is performed without the need to remove or add additional components to the lawn mower. The lawn mower includes a power source, a pair of front ground engaging wheels, a pair of rear ground engaging wheels, and a cutting blade connected to the power source. The lawn mower also includes a mower deck having a top panel surrounded by a downward extending skirt forming a cutting chamber in the underside the mower deck. The cutting chamber houses the cutting blade. The mower deck has an opening therein forming a passageway through which grass clippings exit the cutting chamber during select modes of operation. The lawn mower also includes a grass-collecting hopper removably mounted on the mower deck, the grass-collecting hopper having a basket portion for receiving grass clippings cut by the cutting blade and a multi-station mounting portion configured to interface with the opening in the mower deck in a number of different orientations. The mounting portion includes a mulching station that configures the lawn mower to operate in a mulching mode, a bagging station that configures the lawn mower to operate in a bagging mode, and a discharge station that configures the lawn mower to operate in a discharge mode. When the grass-collecting hopper is mounted on the mower deck, one of the stations interfaces with the opening in the mower deck to configure the lawn mower for the desired mode of operation.
[0010] Another aspect of the invention is a multi-use lawn mower capable of selectively bagging grass clippings or returning the grass clippings on the lawn. The lawn mower includes a power source, a cutting blade connected to the power source, and a mower deck forming a cutting chamber in the underside the mower deck. The cutting chamber houses the cutting blade. The mower deck has an opening therein forming a passageway through which grass clippings exit the cutting chamber during select modes of operation. The lawn mower also includes a grass-collecting hopper removably mounted on the mower deck. The grass-collecting hopper has a basket portion for receiving grass clippings cut by the cutting blade and a multi-station mounting portion configured to interface with the opening in the mower deck in a plurality of orientations. The mounting portion includes a bagging station that configures the lawn mower to operate in a bagging mode, and at least one other station that configures the lawn mower to operate in a mode that returns the grass clippings to the lawn. When the grass-collecting hopper is mounted on the mower deck, one of the plurality of stations interfaces with the opening in the mower deck to configure the lawn mower for the desired mode of operation.
[0011] In another aspect, the invention is directed to a multi-use lawn mower capable of selectively operating in a mulching mode of operation, a side-discharge mode of operation, or a bagging mode of operation. The lawn mower includes a power source, a pair of front ground engaging wheels, a pair of rear ground engaging wheels, and a cutting blade connected to the power source. The lawn mower further includes a mower deck that forms a cutting chamber in the underside the mower deck, the cutting chamber housing the cutting blade. The mower deck has an opening therein that forms a passageway through which grass clippings exit the cutting chamber during select modes of operation. The lawn mower also includes a grass-collecting hopper removably mounted above and generally over the center of the mower deck such that substantially the entire hopper is positioned between the front and rear ground engaging wheels. The grass-collecting hopper has a basket portion for receiving grass clippings cut by the cutting blade and a multi-station mounting portion configured to interface with the opening in the mower deck in a plurality of orientations. The basket portion and mounting portion are molded together and components that comprise the different stations of the mounting portion are molded into the mounting portion so that the grass-collecting hopper is a single unitary part. The mounting portion includes a mulching station that configures the lawn mower to function as a mulching mower, a bagging station that configures the lawn mower to function as a bagging mower, and a side-discharge station that configures the lawn mower to function as a side-discharge mower. When the multi-station mounting portion mounts the grass-collecting hopper on the mower deck, a single one of the stations interfaces with the opening in the mower deck to configure the lawn mower for the selected mode of operation.
[0012] These and other features and advantages of this invention are described in, or are apparent from, the following detailed description of various exemplary embodiments of the systems and methods according to this invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] The above mentioned and other features of this invention will become more apparent and the invention itself will be better understood by reference to the following description of embodiments of the invention taken in conjunction with the accompanying drawings, wherein:
[0014] FIG. 1 is perspective view of a lawn mower according to one embodiment of the invention;
[0015] FIG. 2 is a partially exploded perspective view of the lawn mower of FIG. 1 illustrating a grass-collecting hopper;
[0016] FIG. 3 is a partially exploded and cutaway perspective view of the mower deck and grass-collecting hopper of the lawnmower FIG. 1 ;
[0017] FIG. 4 is a bottom perspective view of a mounting portion of the grass-collecting hopper of FIG. 2 ;
[0018] FIG. 5A is an enlarged perspective view of a mulching station on the grass-collecting hopper of FIG. 4 ;
[0019] FIG. 5B is a view of the grass-collecting hopper and mower deck illustrating the flow of grass clippings when the mower is in a mulching mode of operation;
[0020] FIG. 6A is an enlarged perspective view of a discharge station on the grass-collecting hopper of FIG. 4 ;
[0021] FIG. 6B is a view of the grass-collecting hopper and mower deck illustrating the flow of grass clippings when the mower is in a discharge mode of operation;
[0022] FIG. 7A is an enlarged perspective view of a bagging station on the grass-collecting hopper of FIG. 4 ; and
[0023] FIG. 7B is a view of the grass-collecting hopper and mower deck illustrating the flow of grass clippings when the mower is in a bagging mode of operation.
[0024] Corresponding reference characters indicate corresponding parts throughout the views of the drawings.
DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS
[0025] The invention will now be described in the following detailed description with reference to the drawings, wherein preferred embodiments are described in detail to enable practice of the invention. Although the invention is described with reference to these specific preferred embodiments, it will be understood that the invention is not limited to these preferred embodiments. But to the contrary, the invention includes numerous alternatives, modifications and equivalents as will become apparent from consideration of the following detailed description.
[0026] Referring now to the Figures, one embodiment of a lawn mower according to the invention is shown generally at 10 in FIGS. 1 and 2 . The lawn mower 10 has mower body 12 comprising a mower deck 14 at least partially covered by a housing 16 . Front ground engaging wheels 18 are provided at the front of the mower body 12 and rear ground engaging wheels 20 are provided at the rear of the mower body 12 . Desirably, the rear wheels 20 constitute drive wheels for the lawn mower 10 , although the front wheels 18 may also be used as the drive wheels or the lawn mower may be manually propelled without departing from the scope of the invention. A handle 22 extends rearward from the mower body 12 to permit an operator to maneuver the lawn mower 10 . The handle 22 has a conventional operator presence bail 24 and a speed control rod 26 as is known in the art. Although the invention is described herein as part of a walk-behind mower, one skilled in the art will understand that the invention may also be used on a riding lawnmower without departing from the scope of the invention.
[0027] As best seen in FIG. 3 , in one embodiment the mower deck 14 is fabricated with a generally horizontal top panel 30 surrounded by a downward extending skirt 32 to form a cutting chamber 34 in the underside the mower deck 14 . However, other shapes for the mower deck can be selected using sound engineering judgment provided the mower deck forms a suitable cutting chamber. As is understood in the art, a grass cutting blade 36 is provided in the cutting chamber 34 of the mower deck 14 . A power source, such as a gasoline powered engine 38 is mounted on the mower body 12 for rotating the cutting blade 36 and desirably driving the rear wheels 20 . However, it is understood that the power source 38 may be an electric motor without departing from the scope of the invention. The power source 38 has an output shaft (not shown) that is operatively connected to the drive wheels and the cutting blade 36 through transmission means well understood in the art. Therefore, further description of the transmission means need not be provided herein.
[0028] A grass-collecting hopper 40 is removably mounted on the mower deck 14 . The grass-collecting hopper 40 comprises a bottom portion 41 and a basket portion 42 configured to receive and hold the grass clippings. Referring also now to FIG. 4 , the basket portion 42 has an upper rim 44 containing a plurality of lift handles 46 molded therein for lifting and carrying the hopper 40 . The basket portion 42 desirably contains mesh openings (not shown) to aid with air flow out of the basket portion 42 so that the grass clippings can be effectively deposited in the hopper 40 . In one embodiment, the grass-collecting hopper 40 is molded as a single integral piece of polypropylene such that the hopper is somewhat stiff so that it retains it shape to aid in placement onto the mower deck 14 when empty. However, it is noted that other like materials that enable the manufacture of a long-lasting, durable part may be used. It is further to be understood that the grass-collecting hopper 40 may comprise several different components that are glued, snapped or welded together or otherwise fastened together with screws, rivets or other fasteners without departing from the scope of the invention.
[0029] As best seen in FIG. 2 , the housing 16 defines a cavity 50 configured to receive the grass-collecting hopper 40 so that the hopper can mount above the top panel 30 of the mower deck 14 . In the embodiment illustrated, the grass-collecting hopper 40 is mounted above and generally over the center of the mower deck 14 such that substantially all of the grass-collecting hopper 40 is positioned between the front and rear wheels 18 , 20 when in its operational position. While the position of the hopper 40 in the illustrated embodiment is desirable, one skilled in the art will understand that other embodiments are contemplated that may position the hopper 40 in other locations on the mower body 12 such that a substantial portion of the hopper is behind the rear wheels 20 or to the side of the mower deck 14 without departing from the scope of the invention.
[0030] The housing 16 contains a flap 52 that covers the grass-collecting hopper 40 when it is mounted in the cavity 50 . Desirably, the flap 52 is attached to the housing 16 with a hinge 54 so that the flap 52 can be pivoted to enable access to the grass-collecting hopper 40 for easy insertion and removal of the hopper into and out of the cavity 50 . Thus, with the flap 52 in the open position, the user can lift the grass-collecting hopper 40 out of the cavity 50 and carry the hopper to a suitable grass disposal location to dump and dispose of the grass clippings collected in the hopper. Alternately, the flap 52 may be made part of the grass-collecting hopper 40 without departing from the scope of the invention. In the illustrated embodiment, the mower deck 14 has a circumferential ridge 56 extending generally around the outer circumference of the top panel 30 . The ridge 56 engages the grass-collecting hopper 40 to secure the hopper in the cavity 50 .
[0031] As best seen in FIG. 3 , an opening 58 is formed in the mower deck 14 to permit grass clippings cut by the cutting blade 36 to exit the cutting chamber 34 . Desirably, the opening 58 is in the top panel 30 of the mower deck 14 and is located to the rear and toward one side of the deck as illustrated in FIG. 3 . However, the opening 58 may be located in other positions in the mower deck 14 using sound engineering judgment without departing from the scope of the invention. According to the invention, the grass-collecting hopper 40 selectively interfaces with the opening 58 in the mower deck 14 to determine the mode of operation of the lawn mower 10 as will now be discussed.
[0032] Turning now to FIG. 4 , a mounting portion 60 of the grass-collecting hopper 40 comprises a plurality of stations configured to interface with the mower deck 14 of the lawn mower 10 . In one embodiment, the mounting portion 60 is the bottom portion 41 of the grass-collecting hopper 40 and comprises three separate stations. The three stations will be described below as a mulching station 64 , a bagging station 66 and a discharge station 68 , because when the particular station interfaces with the opening 58 in the mower deck 14 , the designated station ( 64 , 66 or 68 ) causes the lawn mower 10 to operate as a mulching mower, a bagging mower and a side-discharge mower, respectively. Desirably, the mounting portion 60 contains the three stations illustrated in FIG. 4 . However, one skilled in the art will understand that the mounting portion 60 may contain only two stations without departing from the scope of the invention. In such embodiment, it is preferable that the mounting portion 60 have a bagging station and a station that returns the grass clippings to the lawn, such as either a mulching station or a discharge station. Desirably, the components comprising the stations 64 , 66 , 68 are molded into the mounting portion 60 such that the grass-collecting hopper 40 is made as a single unitary part. However, the components comprising the stations 64 , 66 , 68 may be glued, welded, attached with fasteners or otherwise affixed to the hopper 40 without departing from the scope of the invention.
[0033] To aid in the convenience of using the lawn mower 10 , it is desirable that the grass-collecting hopper 40 be the only component necessary to configure the lawn mower 10 for the particular mode of operation desired. Therefore, it is not necessary to install or remove additional components from the lawn mower in order to reconfigure the mower 10 between the bagging, discharge and mulching operational modes. In the illustrated embodiment, the grass-collecting hopper 40 has a generally triangular layout with each station 64 , 66 , 68 forming one corner of the triangle so that the stations are spaced about 120 degrees apart around the circumference of the bottom portion 41 of the hopper 40 . To select the mode of operation, the operator simply positions the grass-collecting hopper 40 such that the desired station ( 64 , 66 or 68 ) interfaces with the opening 58 in the mower deck 14 . To switch modes of operation, the operator simply needs to remove the grass-collecting hopper 40 and reposition it (as illustrated by the arrows in FIG. 2 ) so that the station ( 64 , 66 or 68 ) corresponding to the desired mode of operation interfaces with the opening 58 in the mower deck 14 .
[0034] As illustrated in FIGS. 4 , 5 A and 5 B, the mulching station 64 comprises a plug 70 extending downward from the bottom portion 41 of the grass-collecting hopper 40 . The plug 70 has a shape corresponding to the shape of the opening 58 in the mower deck 14 , and when the grass-collecting hopper 40 is mounted on the mower deck 14 such that the plug 70 interfaces with the opening 58 , the plug 70 substantially fills the opening 58 such that grass clippings are prevented from passing through the opening 58 . Thus, the plug 70 substantially seals the opening 58 causing the grass clippings to remain in the cutting chamber 34 as illustrated by the pathway 76 in FIG. 5B so that the cuttings are repeatedly chopped into smaller clippings as in a conventional mulching mower.
[0035] As best seen in FIGS. 4 , 6 A and 6 B, the discharge station 68 comprises a skirt 80 extending from the bottom portion of the hopper that engages the opening 58 in the mower deck 14 such that at least a portion of the skirt is received about the outer circumference of the opening. The skirt 80 directs the grass clippings so that they pass out of the cutting chamber 34 through the opening 58 in the mower deck 14 and through a discharge passageway 82 formed by a chute 84 ( FIG. 3 ) mounted on the mower deck 14 such that they are discharged outwardly on the ground to the side of the lawn mower 10 as illustrated by the pathway 86 in FIG. 6B . As best seen in FIGS. 3 and 4 , the skirt 80 forms a wall having the general shape of the opening 58 with the side adjacent the chute 84 being left open so that grass clippings are free to pass through the chute.
[0036] As best seen in FIGS. 4 , 7 A and 7 B, the bagging station 66 comprises a ramp 90 leading to an aperture 92 in the bottom portion 41 of the grass-collecting hopper 40 . An end wall 94 effectively blocks the chute 84 to prevent the grass clippings from being discharged to the side of the mower 10 . The ramp 90 guides the grass clippings from the opening 58 in the mower deck 14 through the aperture 92 in the bottom portion 41 and up into the grass-collecting hopper 40 so that the clippings are collected in the hopper 40 . Thus, when the grass-collecting hopper 40 is mounted such that the bagging station 66 interfaces with the opening 58 in the mower deck 14 , the grass cut by the cutting blade 36 is received and collected in the basket portion 42 of the hopper 40 as illustrated by the pathway 96 illustrated in FIG. 7B . Desirably, the ramp 90 extends into the basket portion 42 of the hopper 40 to maintain a pathway for the grass clippings as they enter the basket portion so that they do not fall and clump near the aperture 92 and impede the collection of additional grass clippings at least until the basket is substantially full.
[0037] As briefly set forth above, the plug 70 , skirt 80 and ramp 90 are desirably molded as part of the bottom portion 41 of the hopper 40 . Therefore, when the operator desires to select a certain mode of operation for the lawn mower 10 , the operator simply positions the grass-collecting hopper 40 so that the station 64 , 66 , 68 corresponding to the desired mode of operation interfaces with the opening 58 in the mower deck 14 . Suitable markings (not shown) can be placed on the upper rim 44 of the grass-collecting hopper 40 to visually aid the operator in correctly positioning the hopper 40 in the proper orientation. Accordingly, the operator does not need to add or remove any components to the lawn mower 10 in order to change modes of operations, but must only re-position the grass-collecting hopper 40 to the selected position. Desirably, each station 64 , 66 , 68 has a shape corresponding to the opening 58 in the mower deck 14 such that when correctly positioned in the cavity 50 , the hopper 40 snaps or locks in place to help securely mount and discourage misplacement of the hopper. Additionally, as best seen in FIG. 3 , the top panel 30 of the mower deck 14 may have features that receive the stations ( 64 , 66 , 68 ) not engaged with the opening 58 to aid in securely affixing the hopper 40 to the mower deck. Additionally, the stations 64 , 66 , 68 permit a gap between the central surface of the bottom portion 41 of the hopper 40 and the mower deck 14 so that suitable connecting means (not shown) can connect the cutting blade 36 with the power source 38 .
[0038] While this invention has been described in conjunction with the specific embodiments described above, it is evident that many alternatives, combinations, modifications and variations are apparent to those skilled in the art. Accordingly, the preferred embodiments of this invention, as set forth above are intended to be illustrative only, and not in a limiting sense. Various changes can be made without departing from the spirit and scope of this invention. | A multi-use lawn mower capable of operating as a mulching, side-discharge, or a bagging mower. The lawn mower ( 10 ) includes; a mower deck ( 14 ) having an opening ( 58 ) therein forming a passageway through which grass clippings exit the cutting chamber during select modes of operation. The lawn mower also includes a grass-collecting hopper ( 40 ) removably mounted on the mower deck ( 14 ), the grass-collecting hopper ( 40 ) having a basket portion ( 42 ) for receiving grass clippings cut by the cutting blade ( 36 ) and a multi-station mounting portion ( 60 ) configured to interface with the opening ( 58 ) in the mower deck in a plurality of orientations. The mounting portion includes a mulching station ( 64 ) that configures the lawn mower to function as a mulching mower, a bagging station ( 66 ) that configures the lawn mower to function as a bagging mower, and a side-discharge station ( 68 ) that configures the lawn mower to function as a side-discharge mower. When the multi-station mounting portion mounts the grass-collecting hopper on the mower deck, a single one of the stations interfaces with the opening in the mower deck to configure the lawn mower for desired mode of operation. | 0 |
BACKGROUND OF THE INVENTION
The present invention relates to a control arrangement for a hydraulic force transmission to be used especially for a hydraulically operated load lifting and lowering device on agricultural vehicles. Such control arrangements are known in the art in which hydraulic fluid under pressure from a pump is transmitted over a precontrol slide and a blocking device to the hydraulically operated load lifter, whereby the precontrol slide controls the main control slide of the arrangement. In this arrangement it is necessary that the main control slide, the precontrol slide and the blocking device are dimensioned for the large working fluid stream. This prevents a compact construction. In addition, this known arrangement has a relatively long pressure channel for the operating pressure fluid, which leads to an increased flowthrough resistance. Furthermore, in this known arrangement the auxiliary slide forms part of a four-port-two-position valve which is relatively complicated. Since in this known arrangement a continuous control oil stream flows in the neutral position of the arrangement over the auxiliary slide, the latter can also not build too small which again prevents a compact construction. Furthermore, the continuous control oil stream produces additional energy losses. With this known arrangement, the relief of a control chamber coordinated with the main control slide is also influenced by the auxiliary slide. Thereby a certain movement of the auxiliary slide shall assure that there will never occur such a throttling operation that the amount of oil delivered by the pump can just pass through a release opening at the prevailing pressure relationships, so that the pump has to work against an unnecessarily high pressure. This procedure, called for short "tight throttling", may quickly lead to a destruction of the pump. While with the known control arrangement such "tight throttling" is prevented during the pressure increase phase, that is during shifting of the precontrol slide from the neutral position to the lifting position, it is possible that during reverse shifting of the precontrol slide conditions may occur which will result in tight throttling, which evidently is of considerable disadvantage. An additional disadvantage of the known arrangement is that various dimensions of bores and control edges with respect to each other are critical. A further disadvantage of this known arrangement is that during an eventual loading of the fluid stream which is passed from the main control slide into the return conduit, by an additional consumer in the return conduit and by simultaneous lowering of the load of the first consumer, a pressure can be created in the blocking device which leads to a damage of the same.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a control arrangement for a hydraulically operated load lifting device which avoids the disadvantages of such arrangements known in the art.
It is an additional object of the present invention to provide a control arrangement of the aforementioned kind which can be constructed in a more compact manner than known control arrangements of this kind.
It is a further object of the present invention to provide a control arrangement in which the aforementioned tight throttling is positively prevented during movement of the precontrol slide in either direction.
With these and other objects in view, which will become apparent as the description proceeds, the arrangement for controlling the flow of hydraulic fluid under pressure to and from a hydraulic consumer, especially a hydraulically operated load lifter, mainly comprises a housing formed with two bores therethrough, a main control slide axially movable in one of the bores, a precontrol slide axially movable in the other of said bores, in which the precontrol slide is provided with an axial bore closed at opposite ends and an auxiliary slide axially movable in the aforementioned axial bore as a control slide, blocking means in the housing between the precontrol slide and the consumer and controlled by the precontrol slide, the one bore being closed at opposite ends forming between one of the closed ends and the facing end of the main control slide a spring chamber, the other bore in the housing forming about the precontrol slide an inlet chamber, a return chamber and a control chamber located between the aforementioned two chambers, the precontrol slide having a first control edge controlling flow of fluid between said control chamber and the return chamber and a second control edge controlling flow of fluid between the control chamber and the inlet chamber, the bore in the control slide forming between one of the closed ends and said auxiliary slide a pressure chamber, a passage through the auxiliary slide connecting the control chamber with the pressure chamber, a throttle in this passage, a source of fluid under pressure, a pressure channel leading from the main control slide directly to the blocking means, and connectable by the main control slide to the source, a return conduit, and control passage means leading from the source over the precontrol slide and the auxiliary slide to the aforementioned spring chamber and connectable by the main control slide to the return conduit, the second control edge forming a throttle passage in the control passage means and the latter connecting the control chamber with the spring chamber, whereas the auxiliary slide controls a bypass leading from the inlet chamber to the control chamber, which bypass being parallel to the passage leading over the second control edge and parallel to the passage in which the throttle is located.
The pressure chamber communicates with the control chamber in either position of the auxiliary slide only over the aforementioned throttle, which will assure a damping of the movement of the main control slide during its movement from a position initiating lifting of a load to its neutral position.
The novel features which are considered as characteristic for the invention are set forth in particular in the appended claims. The invention itself, however, both as to its construction and its method of operation, together with additional objects and advantages thereof, will be best understood from the following description of specific embodiments when read in connection with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic longitudinal cross-section through the control arrangement according to the present invention, with the various elements of the control arrangement shown in neutral position;
FIG. 2 is a partial cross-section through another auxiliary slide; and
FIG. 3 is a longitudinal cross-section through part of another control arrangement.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring now to the drawing and more specifically to FIG. 1 of the same, there is shown a control arrangement 10 to be used as control arrangement for a hydraulically operated lifting device of agricultural vehicles, especially tractors or combines.
The control device 10 is provided with a housing 11 in which in corresponding bores a main control slide 12, a precontrol slide 13 with an auxiliary slide 14 arranged therein, as well as a blocking device 15 comprising a valve 16 and a pushing piston 17, are arranged parallel to each other.
The main control slide 12 is axially guided in a bore 18 which is formed with adjacent annular enlargements forming, starting from the region of the left end of the bore 18, a spring compartment 19, a discharge compartment 21, an outlet compartment 22, an inlet compartment 23, a run-on compartment 24 and damping compartments 25 and 26. The main control slide 12 is loaded at one end by spring 27 arranged in the spring compartment 19, as well as from the fluid pressure prevailing in the spring compartment 19, and on the other end by the fluid pressure prevailing in the damping compartment 26. The damping compartments 25 and 26 are connected by a channel 29 and over a one-way valve 28 with the inlet compartment 23. The inlet compartment 23 is connected by a conduit with the pump 31, and from the run-on compartment 24 a conduit 32 leads, over an additional consumer 33 located therein, to the tank 30. A damping slide 34 is arranged in an axial bore of the main control slide 12, which controls the connection between the damping compartments 25 and 26 and the position of the damping slide 34 is controlled depending on the pressures residing on opposite ends thereof. The control flow of the fluid stream under pressure is pumped by the pump 31 from the inlet compartment 23 selectively into the run-on compartment 24 or the outlet compartment 22, the main control slide 12 has a piston section 35 with a fine control chamber 36.
The precontrol slide 13 is arranged in a second bore 38 extending parallel to the bore 18. The bore 38 is again provided with a plurality of adjacent annular enlargements forming, starting from the left end of the bore 38 as viewed in the drawing, a first return chamber 39, a first control chamber 41, an inlet chamber 42, a second control chamber 43, a second return chamber 44 and a third return chamber 45. The first return chamber 39 and the second return chamber 44 are relieved toward the tank 30. The inlet chamber 42 is connected by an inlet channel 46 with the inlet compartment 23 at the main control slide 12, whereas a control channel 47 leads from the first control chamber 41 to the spring compartment 19 of the main control slide 12. The inlet channel 46 and the control channel 47 form part of a control conduit system 50 which leads from the pump 31 to the return conduit and in which the precontrol slide 13, the auxiliary slide 14, and the spring compartment 19 are arranged. Annular grooves provided on the peripheral surface of the precontrol slide 13 form thereon five control edges 48, 49, 51, 52 and 53, of which the first control edge 48 controls the connection from a pressure chamber 54 formed in the precontrol slide 13 over radial bores 55 to the first return chamber 39. The second control edge 49 controls the connection from the inlet chamber 42 to the first control chamber 41. The third control edge 51 and the fourth control edge 52 control the connections from the second control chamber 43 to the inlet chamber 42, respectively to the second return chamber 44. The fifth control edge 53 throttles, during lowering of a load of a hydraulically operated load lifter 56, the lowering speed. The load lifter 56 is schematically shown in FIG. 1 as a fluid operated cylinder and piston unit, and the piston rod of the piston in the cylinder of the unit abuts against a crank lever 60 which is connected to a linkage 60' having an arm carrying a plow 60" which is to be lifted during feeding of pressure fluid into the cylinder of the unit and which is to be lowered during outflow of such pressure fluid from the unit. The first and second control edges 48 and 49 are so arranged and dimensioned that they will provide a positive overlapping and in addition they work in opposite directions. From the pressure chamber 54 in the precontrol slide 13 a coaxial bore leads to a space in which a coil spring 58 is arranged, which biases an auxiliary slide 14 guided in the longitudinal bore 57 toward the left, as viewed in the drawing. The auxiliary slide 14 forms part of a three-port, two-position valve 59 and serves to prevent the above-mentioned so-called "tight throttling." An elongated annular groove 61 divides the auxiliary slide 14 in an end section 62 and a piston section 63 and the control edges of these two sections are likewise constructed with positive overlapping. In the illustrated starting position of the auxiliary slide 14, the end section 62 controls the connection from the pressure chamber 54 over the groove 61 to the radial bores 64 which, independent of the respective position of the precontrol slide 13, are always in connection with the first control chamber 41. At the same time the piston section 63 closes in the illustrated starting position of the auxiliary slide 14 the radial bores 65 which lead into an annular groove on the peripheral surface of the precontrol slide 13 adjacent the second control edge 49 thereof and which is always connected with the inlet chamber 42. A connection parallel to the connection controlled by the end section 62 leads from the first control chamber 41 over a cross bore 66 in the region of the groove 61, an axial bore 67 as well as a throttle 68 to the pressure chamber 54. The precontrol slide 13 is biased by a spring 69 toward the right, as viewed in FIG. 1, and is actuated against the pressure of the spring 69 by a non-illustrated regulating linkage acting on the right end of the precontrol slide 13 projecting beyond the housing 11. The auxiliary slide 14 controls with its piston section 63 a connection from the inlet chamber 42 to the control chamber 41, which is designated as bypass 60 and which is parallel to the connection over the second control edge 49 and also parallel to the throttle 68.
The opening piston 17 of the blocking device 15 is slidably arranged in a bore 71 of the housing 11 and the bore is formed with a plurality of adjacent annular enlargements forming, starting from the left end of the bore 71, a return space 72, an annular inlet space 73, an annular consumer space 74, an annular lowering space 75, as well as an annular control space 76. A pressure channel 77 leads from the inlet space 73 directly to the outlet compartment 22 on the main control slide 12. The housing 11 is preferably formed by a cylindrical casting and the aforementioned connection is in practice advantageously formed by a short cross channel in the casting. A consumer conduit 78 leads from the consumer space 74 over the valve 16 to the load lifter 56. The lowering space 75 is connected by a passage 79 with the third return chamber 45 at the precontrol slide 13. A channel 81 provided with a throttle 82 leads from the control space 76 into the second control chamber 43 at the precontrol slide 13. The return space 72 is relieved of pressure by being connected to the tank 30. The opening piston 17 is provided on the peripheral surface thereof with a first control land 83 and a second control land 84. A spring 85 arranged in a coaxial blind bore of the piston 17 presses a piston 86 in this blind bore against an abutment 87 and forms thereby a force limiting arrangement 88. The piston 86 abuts against one end of a plunger 89 which is guided for movement in axial direction in the housing 11 and which cooperates with the valve member 91 of the valve 16, which in turn is already precontrolled by means of a ball valve 92 arranged in the interior thereof. The valve member 91 separates in the illustrated starting position, in which it is held by a spring 90 in a spring chamber 90', a first chamber 93 at the inlet side of the valve 16 from a second chamber 94 arranged at the outlet side of this valve.
The action of the control arrangement 10 is described in the following, insofar as it is necessary for the understanding of the invention.
In the shown neutral starting position of the precontrol slide 13, the main control slide 12 is in the illustrated position. In this position the main control slide 12 controls the flow of oil pumped by the pump 31 into the inlet compartment 23 over the fine control chamber 36 into the run-on compartment 24 and to the auxiliary consumer 33 in the conduit 32 to the tank 30. A pressure difference will thereby be created from the inlet compartment 23 to the run-on compartment 24, since the pump pressure in the damping compartment 26 has to balance the force of the springs 27. The spring chamber 19 itself is relieved of pressure over the auxiliary slide 14, the first control edge 48, of the precontrol slide 13 towards the tank 30, since the auxiliary slide 14 has the illustrated starting position and therefore does not close the control passage system 50 to the tank, nor does it throttle this system. The flow of fluid to the load lifter 56 is prevented in the shown neutral position by the valve 16. The consumer space 74 of the opening piston 17 is relieved of pressure over the pressure channel 77, the outlet compartment 22, the discharge compartment 21 towards the tank 30. At the same time pressure in the control space 76 is relieved over the channel 81, the first control chamber 43 and the second control chamber 44 to the tank 30. The control pressure residing due to the pressure gradient in the inlet chamber 42 can, therefore, not lead, due to leaking control oil, to an undesired actuation of the opening piston 17.
In order to produce a lifting movement of the load lifter 56 by feeding pressure fluid to the right side of the piston located therein, the precontrol slide 13 is moved against the force of the spring 69 towards the left, as viewed in the drawing, into a lifting position. Thereby the first control edge 48 of the precontrol slide 13 closes the connection to the tank 30 and interrupts the control conduit system 50 leading from the spring compartment 19 to the tank 30. Subsequently thereto the second control edge 49 opens the connection between the inlet chamber 42 to the first control chamber 41 and the control oil flows over the control channel 47 into the spring compartment 19. The thus pressure balanced main control slide 12 is moved by the spring 19 toward the right, as viewed in the drawing, and throttles thereby the flow of oil through the return conduit 32 to the consumer 33. This movement of the main control slide 12 toward the right occurs in the beginning without dampening, and is during its further movement damped when the pressure dependent damping slide 34 reverses. At the mentioned movement of the main control slide 12 towards the right, it separates first the outlet compartment 22 from the discharge compartment 21 and then connects the outlet compartment 22 with the inlet compartment 23. Oil from the inlet compartment 23 can now pass over the pressure channels 77 into the inlet space 73 and further over the consumer space 74 at the opening piston 17, the consumer conduit 78 and the valve 16 which operates now as a one-way valve to the load lifter 56, which thus lifts the load connected thereto.
A so-called "tight throttling" is avoided during this lifting process. This tight throttling is known per se for instance from the German Auslegeschrift No. 1,928,896 and designates such a throttling process in which the oil pumped by the pump can just pass through a relief bore at the prevailing pressure conditions, whereby the pump has to work against an exceedingly high pressure and is thereby quickly destroyed. This tight throttling is prevented with the arrangement according to the present invention, due to the sudden movement of the main control slide 12 so that the same may not remain stationarily in an undesired manner in an intermediate position. A creeping approach to an undesired condition of equilibrium is thereby positively prevented. This is obtained by means of the auxiliary slide 14 which acts as a hydraulic snap-switch and controls the bypass 60 in the control conduit system 50. When the first control edge 48 at the precontrol slide 13 closes relief of the control conduit 50 and subsequently thereto the second control edge 59 opens the connection coordinated therewith, the pressure prevailing in the first control chamber 41 may also build up over the radial bore 64, the annular groove 61 on the auxiliary slide 14 in the pressure chamber 54. If the pressure in the latter rises to a predetermined volume, depending on the pressure rise in the inlet compartment 23, then the auxiliary slide 14 snaps over from the shown starting position toward the right to its other end position. Thereby the piston section 63 opens the bypass 60 from the inlet chamber 42 to the first control chamber 41, while the end section 62 closes the connection over the annular groove 61 to the pressure chamber 54. The bypass 60 is, therefore, parallel to the connection over the second control edge 49. The still increasing pressure in the first control chamber 41 may pass at the reversed auxiliary slide 14 over the cross bore 66, the bore 67 and the throttle 68 in the auxiliary slide 14 into the pressure chamber 54 to hold thereby the auxiliary slide 14 securely against the force of the spring 58 in its right end position. Thus, during shifting of the precontrol slide from the neutral to the lifting position a so-called tight throttling is positively prevented, whereby the auxiliary slide 14 operates as a so-called pressure monitor.
If, after the lifting process has been finished, the precontrol slide is again moved from its lifting position to its neutral position, then the so-called "tight throttling" is again prevented by the fast movement of the auxiliary slide 14. During the start of the movement of the precontrol slide 13 towards the right to its neutral position, the second control edge 49 interrupts flow of fluid through the fluid passage system 50, whereas the bypass 60 still remains open. Subsequently thereto, the first control edge 48 opens the connection of the pressure chamber 54 to the tank 30, whereby the pressure in the pressure chamber 54 drops. Only a very small amount of control oil can flow over the throttle 68 from the spring compartment 19 into the pressure chamber 54. If the pressure in the pressure chamber 54 sinks below a predetermined value, then the spring 58 presses the auxiliary slide 14 back into the illustrated starting position, whereby the bypass 60 will be closed. The pressure in the spring compartment 19 is now relieved toward the tank 30 so that the pressure acting in the damping compartment 26 moves the main control slide from its right end position again toward the illustrated middle position in which the connection between the inlet compartment 23 and the run-on compartment 24 is again established. Thus a "tight throttling" is also prevented during such movement due to the sudden reversal of the movement of the auxiliary slide 14 in connection with the oppositely open, respectively closed throttle location in the control circuit. This is advantageously derived in that the auxiliary slide works thereby as a fluid regulating slide which is, however, so arranged that it throttles the fluid stream to an increasing pressure gradient.
In order to lower the load connected to the load lifter 56, that is in order to permit outflow of the fluid from the cylinder compartment to the right side of the piston of the load lifter 56, the precontrol slide 13 is moved from the shown neutral position toward the right into a load lowering position. Thereby the precontrol slide 13 opens with its third control edge 51 the connection from the inlet chamber 42 over the second control chamber 43 and the conduit 81 to the control space 76 at the right end of the opening piston 17 and interrupts at the same time by its fourth control edge 52 flow of fluid from the control space 76 to the tank 30. The control pressure now obtained in the control space 76 presses the piston 17 towards the left, as viewed in the drawing, into another end position. Thereby the plunger 89 opens the precontrolled valve 16 and oil from the cylinder space at the right side of the piston in the load lifter 56 flows now back through the consumer conduit 78 into the consumer space 74, further to the lowering space 75, over the conduit 79 into the third return chamber 45 and from there into the second return chamber 44 to the tank 30. Thereby the return flow may be throttled in any desired manner by fine control chambers provided on the precontrol slide 13. During this lowering operation the control pressure throttled by the main control slide 12 is sufficient for actuating the opening piston 17.
If, however, during the above-described lowering procedure the consumer 13 in the outlet conduit 32 is actuated at the same time, so that in the run-on compartment 24 as well as in the inlet compartment 23 a much higher pressure will occur than the otherwise necessary control pressure, then this higher pressure will act also in the control space 76 onto the opening piston 17. The above-described force limiting arrangement 88 will prevent that an exceedingly large force will be transmitted to the plunger 89, which could lead to a destruction of elements of the blocking arrangement 15.
FIG. 2 shows part of the precontrol slide 13 with a different auxiliary slide 100 arranged therein. The auxiliary slide 100 differs from the auxiliary slide 14 shown in FIG. 1 only in that a wider end section 101 is provided, which also in its starting position closes the unthrottled connection from the first control chamber 41 to the pressure chamber 54, whereby an especially efficient and advantageous damping of the main control slide 12 during its movement from the position "lifting" to the position "neutral" may be obtained, while practically no additional means are necessary. By this movement from the lifting position to the neutral position the main control slide 12 has to displace pressure fluid from the spring compartment 19. This control oil flows from the spring compartment 19 over the control channel 47, the first control chamber 41, the radial bore 64 in the precontrol slide 13, the bore 66, 67 in the auxiliary slide 14 and the throttle 68 into the pressure chamber 54 and over the first control edge 48 to the tank 30. Due to the considerable throttling at the throttle 68 oscillations of the main control slide 12 are positively prevented and an overmovement beyond the neutral position is prevented, even though a relative high pressure in the damping compartments 25, respectively 26, acts on the main control slide 12.
FIG. 3 illustrates part of a modified control arrangement 110, which differs from that shown in FIG. 1 especially by a simpler opening piston 111. In this arrangement the pressure channel 77 leads directly into the chamber 93 at the inlet side of the valve 16. Outflow of fluid from the chamber 93 through the pressure channel 77 is prevented by a one-way valve 112 located therein. A passage 113 connected to the pressure channel 77 between the one-way valve 112 and the chamber 93 leads to the third return chamber 45 at the precontrol slide 13. The annular spaces 73, 74 and 75 shown in FIG. 1 about the closer piston 17 are omitted in the construction shown in FIG. 3.
The operation of the embodiment shown in FIG. 3 is similar to that shown in FIG. 1. During the lifting operation pressure fluid passes over the pressure channel 77 and the valve 16 directly to the load lifter 56, not shown in FIG. 3. The channel 113 is thereby blocked by the precontrol slide 13. During the lowering operation outflow of fluid from the load lifter 56 through the pressure channel 77 is prevented by the one-way valve 112 and the oil will flow from the load lifter 56 over the opened valve 16, the channel 113, the third return chamber 54 and the second return chamber 44 to the tank 30. The control arrangement 110 has the advantage that it is simpler in construction than the control arrangement 10 and that it also permits a quicker changeover from the position "lifting" to the position "lowering" and vice versa.
It will be understood that each of the elements described above, or two or more together, may also find a useful application in other types of control arrangements for a hydraulic force transmission differing from the types described above.
While the invention has been illustrated and described as embodied in an arrangement for controlling flow of hydraulic fluid under pressure to and from a hydraulic consumer, especially a hydraulically operated load lifter, it is not intended to be limited to the details shown, since various modifications and structural changes may be made without departing in any way from the spirit of the present invention.
Without further analysis, the foregoing will so fully reveal the gist of the present invention that others can by applying current knowledge readily adapt it for various applications without omitting features that, from the standpoint of prior art, fairly constitute essential characteristics of the generic or specific aspects of this invention. | A control arrangement for a hydraulic force transmission, especially for a hydraulically operated lifting device on agricultural vehicles comprises, besides a main control slide, a pressure control slide and a blocking device, an auxiliary slide arranged in a bore of the pre-control slide. The hydraulic working fluid is fed from the main slide directly to the blocking device and a special arrangement of the auxiliary slide in the hydraulic control circuit permits a compact and simple construction of the control arrangement, while preventing tight throttling of the fluid in either direction of the flow. | 1 |
TECHNICAL FIELD
[0001] This disclosure relates to environmental systems for heating, ventilation, and/or cooling an environment. More particularly, this disclosure relates to an integrated control device for such systems.
BACKGROUND
[0002] Environmental systems, such as heating, ventilation, and air conditioning (HVAC) systems are used in many commercial and industrial applications, such as in the heating and cooling of buildings. The temperature changing capacity of an environmental system is produced by a heater and/or cooling unit. In the case of heat pumps, the cooling unit and the heater are the same system. A heater can generate heat using, for example, a combustion process, a catalytic process, a refrigeration cycle (e.g., a heat pump), an electrical resistance heating source, and others. Cooling units primarily rely on a refrigeration cycle but other cooling units are known, such as, a thermoelectric devices, evaporative coolers, environmental heat sinks, etc. The environmental system exchanges heat between a fluid, such as air, and the heater and/or cooling unit by forcing the fluid across a heat exchanger, which is in thermal communication with the heater and/or cooling unit.
[0003] A blower fan can be used to force the air through the environmental system (e.g., a forced air heating and cooling system). The forced air is supplied from the heat exchanger to desired locations in the building through air passeageways or ducts.
[0004] The blower fan is rotated by a blower motor. The blower motor can be a brushless DC motor that is controled by a motor controller. The motor controller comprises a microprocessor configured to operate the blower motor in a known manner. Low cost HVAC systems have a motor controller and motor that are configured to operate the blower motor at a single fixed speed. Medium cost systems have a motor controller and motor that are configured to operate the blower motor at multiple fixed speeds. Higher cost systems have a motor controller and motor that are configured to operate the blower motor at varaible speeds. These different configurations can require different components, wiring, software, and combinations of any of the foregoing.
[0005] The environmental system is controlled by a system controller. The system controller recevies inputs including, for example, a control signal from a thermostat. When the system controller determines that heating is desired, the system controller sends an output signal to the heat source to generate heat and sends an output signal to the motor controller. The motor controller then activates and controls the operation of the blower motor. Similarly, when the system controller determines that cooling is desired, the system controller sends an output signal to activate the cooling source and sends an output signal to the motor controller, which activates and controls the operation of the blower motor.
[0006] The required communication between the motor, the motor controller, and the system controller can add expense, complexity, and size to the HVAC system.
SUMMARY
[0007] Disclosed herein is an integrated control device for an environmental system comprising a motor that is in mechanical communication with a device forcing fluid through the environmental system and a controller physically mounted to the motor. The controller includes a processor programmed to control the motor and at least one other internal system of said environmental system in response to a thermostat control signal. The other internal system may comprise a heater and/or cooling unit.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] The present disclosure is described, by way of example, with reference to the accompanying drawings, in which:
[0009] [0009]FIG. 1 is a block diagram of an exemplary embodiment of an integrated control device;
[0010] [0010]FIG. 2 is a schematic view of an exemplary embodiment of a gas furnace having an integrated control device; and
[0011] [0011]FIG. 3 is a perspective view of an exemplary embodiment of the integrated control device of FIG. 2 connected in driving relation to a blower.
DETAILED DESCRIPTION
[0012] Referring now to the Figures and in particular to FIG. 1, an integrated control device 10 for an environmental system is illustrated. Device 10 is configured to integrate an environmental system controller, a motor controller, and a blower motor into a single, simple, and inexpensive unit. Thus, device 10 can reduce the size, expense, and complexity of the environmental system.
[0013] Integrated control device 10 comprises a controller 12 integrated as part of a motor 14 . Controller 12 comprises a processor 16 , a rectifier 18 , and an inverter 20 . Motor 14 is, for example, a brushless DC motor having ferrite magnets. Alternately, motor 14 may be a brushless DC motor having or rare-earth magnets (e.g., neodymium-iron-boron). Motor 14 drives a blower fan (not shown) that moves air across a heating/cooling source 22 .
[0014] Device 10 is configured such that the controller 12 can receive a plurality of inputs 24 and can provide a plurality of outputs 26 to control the operation of motor 14 , source 22 , as well as other portions of the environmental system.
[0015] Inputs 24 may include an input 28 of for power input (e.g., DC or 110/220 volt AC), thermostat inputs, inputs from the heat cooling source, and other inputs necessary for the control and operation of the environmental system.
[0016] Outputs 26 may include a power output to a thermostat (e.g., 24 volt AC), a DC power output to motor 14 , one or more activation signals to source 22 , and other outputs necessary for the control and operation of the environmental system.
[0017] Processor 16 may be a digital signal processor, microprocessor and/or other assorted electronic components well known in the field of electronic control for providing memory, input/output, and processing functions. Processor 16 is programmed to control the operation of the motor 14 .
[0018] If Input 28 is 110/220 Volt AC, rectifier 18 and/or other components are configured to convert 110/220 Volt AC power to DC power. Rectifier 18 thereby provides the DC power to processor 16 and motor 14 , as well as other portions of the environmental system. In an alternative embodiment, input 28 is AC or DC power from an external transformer or other type of power supply.
[0019] Inverter 20 is a switching mechanism (e.g., MOSFET type transistors) configured to selectively apply the DC voltage from the rectifier 18 to the various windings of the motor 14 . Thus, inverter 20 is coupled between the rectifier 18 and the motor 14 . The inverter is controlled by processor 16 to selectively supply the DC voltage across the motor windings to operate the motor.
[0020] Accordingly, device 10 comprises controller 12 integrated into motor 14 and uses inputs 24 and outputs 26 to control the operation of the motor and source 22 . Specifically, integrated control device 10 integrates the functions of a system controller, a motor controller, and a blower motor into a single, simple, and inexpensive unit.
[0021] In addition, device 10 provides the three classes of prior systems (i.e., single fixed speed systems, multiple fixed speed systems, and varaible speed systems) with only a change in software settings. This allows the same device 10 to provide all three classes of systems, which can further reduce the cost of the environmental system.
[0022] Turning now to FIGS. 2 and 3, device 10 is illustrated by way of example in use with a gas furnace 30 . Gas furnace 30 comprises a gas source (not shown) feeding a plurality of burners 34 (only one shown). A solenoid operated gas valve 36 is positioned between the gas source and burners 34 . Gas valve 36 is configured to selectively supply a desired mixture of gas and air to burners 34 . Each burner 34 includes an igniter 38 adapted to selectively ignite the mixture. Device 10 is configured to provide a first output 40 to control the operation of gas valve 36 and a second output 42 to control the operation of igniters 38 .
[0023] Gas furnace 30 also comprises a plurality of heat exchangers 44 in convective and/or conductive communication with the burners 34 such that the combustion of the mixture heats the heat exchangers. Supply air for the combustion process enters the gas furnace 30 and the by-products of the combustion process exit the furnace in a desired manner. For example, the by-products of the combustion process exit the furnace through an exhaust flue. In addition, an exhaust gas blower (not shown) can be configured to aid in venting the combustion by-products from gas furnace 30 .
[0024] Gas furnace 30 also comprises a blower fan 46 in fluid communication with heat exchangers 44 . Blower fan 46 is configured to force a fluid, such as air, through heat exchangers 44 in the direction of arrow 48 . Specifically, motor 14 is configured to rotate a motor shaft 50 , which drives blower fan 46 through a transmission 51 . Transmission 51 may comprise a belt and pulley system, a chain and sprocket system, a gear train system, and others to drive blower fan 46 . As shown, motor 14 is directly connected to blower fan 46 by shaft 51 ; thus shaft 50 is transmission 51 .
[0025] It should be recognized that gas furnace 30 is described herein by way of example as an up-flow gas furnace. Of course, other types of furnaces using heating sources other than combustion and/or furnaces that force the air in other directions through the heat exchangers are contemplated by the present disclosure.
[0026] Device 10 is configured to receive a first input 52 from a thermister 54 , which is provided on the heat exchangers 44 or elsewhere in the system. Input 52 is indicative of the temperature of the air after it has been forced through heat exchangers 44 .
[0027] Device 10 is also configured to provide a third output 56 and to receive a second input 58 from a thermostat 60 . Thermostat 60 may be positioned in a desired location in the building in which gas furnace 30 is installed. Thermostat 60 is a switching device that receives third output 56 from device 10 , and sends second input 58 back to the device when the thermostat detects one or more selected conditions.
[0028] Third output 56 and second input 58 are, for example, control voltage signals (e.g., 24 volts AC). Thermostat 60 is configured to measure the ambient temperature in the building in which gas furnace 30 is installed. An operator adjusts a desired target temperature-using thermostat 60 . Thermostat 60 provides second input 58 to device 10 when the thermostat determines additional heat is needed to maintain the target temperature.
[0029] Upon receiving second input 58 , device 10 starts gas furnace 30 to provide heat to the building. Specifically, integrated control device 10 activates motor 14 to operate blower fan 46 . Device 10 sends first output 40 to gas valve 36 , which opens the valve and provides the gas supply 32 to the burners 34 . Additionally, integrated control device 10 sends second output 42 to igniters 38 to ignite the mixture in burners 34 .
[0030] Integrated control device 10 can continuously monitor first input 52 from thermister 54 while gas furnace 30 is operating. Device 10 may control the speed of the blower fan, the state of the gas valve, and/or the number of burners in operation to manage the air temperature exiting the heat exchangers 44 to a desired temperature.
[0031] Thermostat 60 stops sending second input 58 to device 10 when the thermostat heat is no longer required to maintain the target temperature.
[0032] Device 10 stops gas furnace 30 when second input 58 is no longer provided by thermostat 60 . Specifically, integrated control device 10 deactivates motor 14 to stop blower fan 46 . Device 10 stops sending first output 40 to the gas valve 36 , which closes the valve and shuts off gas supply 32 to burners 34 . In this example, gas valve 36 is normally biased to a closed position such that the removal of first output 40 causes the valve to open (e.g., a normally closed valve). Of course, other types of valves are contemplated for use with the present disclosure. For example, integrated control device 10 may send a second first output signal 40 to close gas valve 36 (a two-way actuated valve).
[0033] Integrated control device 10 may also be configured to receive a third input 62 from an exhaust gas pressure sensor 64 . Third input 62 can be indicative of a pressure of the combustion by-products in an exhaust vent or flue. Device 10 can modify, adjust, or suppress the operation of the gas furnace based upon third input 62 . For example, integrated control device 10 can control the pressure in the exhaust vent by turning on and off or modifying the speed of an exhaust gas fan 66 , which aids in venting the combustion by-products from gas furnace 30 , by closing gas valve 36 to one or more burners 34 , and others.
[0034] Accordingly, and in this manner integrated control device 10 is configured to maintain the ambient temperature in the building to a desired level. It should be recognized that the operation of gas furnace 30 by integrated control device 10 is described above by way of example only. Of course, integrated control device 10 can operate gas furnace 30 using more than, less than, and/or different inputs and outputs than those described above. For example, integrated control device 10 may receive inputs a flame sensor, a current shunt voltage resistor, and others. Device 10 may provide outputs to an exhaust fan (not shown), a humidifier (not shown), etc.
[0035] Integrated control device 10 eliminates the wiring harness between the system controller and the motor controller, and between the motor controller and the motor of prior systems. Thus, the high level of integration provided by integrated control device 10 reduces the number of components, which can provide a corresponding increase in reliability.
[0036] It should also be noted that the terms “first”, “second”, and “third” may be used herein to modify elements performing similar and/or analogous functions. These modifiers do not imply a spatial, sequential, or hierarchical order to the modified elements, unless otherwise indicated.
[0037] While the invention has been described with reference to one or more an exemplary embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention, but that the invention will include all embodiments falling within the scope of the appended claims. | An integrated control device for an environmental system comprises a motor that is in mechanical communication with a device forcing fluid through the environmental system and a controller physically mounted to the motor. The controller includes a processor programmed to control the motor and at least one other internal system of said environmental system in response to a thermostat control signal. The other internal system may comprise a heater and/or cooling unit. | 1 |
FIELD
[0001] The invention is in the field of membrane processes for water treatment such as microfiltration, ultrafiltration and reverse osmosis.
BACKGROUND
[0002] The following discussion is not an admission that anything discussed below is common general knowledge or citable as prior art.
[0003] Some water treatment processes use multiple membrane treatment steps in series. In particular, microfiltration (MF) or ultrafiltration (UF) membranes may be used to pre-treat water prior to a nanofiltration (NF) or reverse osmosis (RO) step. Such combined processes are used for example in sea water desalination, wastewater recovery and in some industrial water treatment plants.
[0004] For example, a presentation entitled “Desalination Technology Overview” presented by James C. Lozier at the April 2011 Water Resources Research Center Conference in Yuma, Ariz., USA, describes a seawater RO plant. In this plant, there are three trains of UF or MF immersed membranes each having a suction pump delivering permeate to a break tank. From the break tank, water is pumped through a set of parallel RO trains. The RO permeate is stored in tanks and then transferred to a distribution system.
INTRODUCTION
[0005] The following section is intended to introduce the reader to the detailed description to follow and not to limit or define any claims. One or more inventions may be comprised of a combination or sub-combination of elements or steps described in this introduction or in other parts of this specification.
[0006] A water treatment system combines a microfiltration or ultrafiltration membrane system with a downstream reverse osmosis membrane system. The UF or MF membrane system has multiple trains of immersed MF or UF membrane modules. The trains are connected to a common set of one or more permeate pumps. The permeate pumps discharge directly into the inlet of an RO feed pump. In a water treatment process, the membrane trains are each subjected to the same suction. The permeate pumps are operated to provide the required flow to the RO feed pump at or above the minimum inlet pressure of the feed pumps.
BRIEF DESCRIPTION OF THE DRAWINGS
[0007] FIG. 1 is a schematic process flow diagram of a water treatment system.
DETAILED DESCRIPTION
[0008] FIG. 1 shows a water treatment system 10 . The water treatment system 10 combines a UF or MF system 12 with an RO system 14 , which may be replaced by a nanofiltration system or a combined nanofiltration and RO system for some applications. The water treatment system 10 may be used, for example, for sea water desalination, for wastewater recovery and reuse, or for various industrial water treatment applications.
[0009] The UF or MF system 12 has many membrane modules that are hydraulically connected to form a train 16 . In particular, all of the membrane modules in a train 16 discharge permeate, alternatively called filtrate, into a common filtrate header 18 . The modules in a train 16 may also be physically connected, or they may be separated into smaller physical groups such as cassettes. The membrane modules may be, for example, ZeeWeed™ modules sold by GE Water and Process Technologies.
[0010] Each train 16 is located in a separate tank 20 . The tanks 20 may be distinct structures or regions separated by partitions in a larger tank. Optionally, two or more trains 16 may be located in a common tank 20 but in that case the two or more trains 16 are treated as one larger train 16 unless they can be separately monitored and individually shut down. Although two trains 16 are shown in FIG. 1 , more trains 16 may be provided. A larger number of trains 16 reduces the effect of one train 16 being temporarily out of service, for example for a deconcentration or cleaning procedure. Further, in the water treatment system 10 there are no pumps dedicated to a individual train 16 and only two valves, and very little if any instrumentation, dedicated to an individual train 16 . Accordingly, the incremental cost of subdividing the total number of membrane modules into a greater number of trains 16 is not large. For example, five or more trains 16 may be used.
[0011] Feed water is provided to the tanks 20 from a feed inlet 22 connected to a feed distribution manifold 24 . The feed distribution manifold 24 is in turn connected to a tank inlet 26 associated with each tank 20 . The tank inlet 26 is located near the bottom of a tank 20 or at least in part below ordinary water levels in the tank 20 . In this way, the division of the total feed flow between the tanks 20 is affected by the relative water level in the tanks 20 . If one train 16 fouls and begins to produces less permeate, the water level in that tank 20 will rise. The rising water level will both reduce the rate of feed flow into thank tank 20 and increase the transmembrane pressure (TMP) across that train 16 until a new equilibrium is reached. Since the train 16 has fouled, its flux will be lower at the new equilibrium but the increase in TMP will moderate the decrease in flux. Conversely, if a first train 16 is more permeable than a second train 16 , the water level in the first tank 20 will be lower than in the second tank 20 . The TMP of the first train 16 will be lower than the TMP of the second train 16 . Although the first train 16 will still have a higher flux, its reduced TMP will reduce the difference in flux between the first and second trains. At an equilibrium condition, more feed water will flow to the first tank 20 . The head loss to the first tank 20 minus the head loss to flow to the second tank 20 will be equal to the difference in water level equal. In this way, feed water is automatically divided between the tanks 20 as required to accommodate different fluxes in each tank 20 , and TMP is automatically adjusted in a way that tends to dampen differences in permeability between the trains 16 .
[0012] Each tank inlet 26 has a feed valve 28 . The feed valve 28 is fully open while the associated train 16 is operating in a permeation phase of its cycle. However, the feed valve 28 is closed when the train 16 enters a deconcentration or cleaning cycle, or during an optional flux test to be described further below. In a deconcentration cycle or cleaning cycle, the feed valve 28 is closed to isolate the associated tank 20 from the feed inlet 22 . A permeate flow control valve (FCV) 30 in the filtrate header 18 is also closed. Optionally, the train 16 may continue to produce permeate for a period of time after the feed valve 28 is closed to reduce the volume of water in the tank 20 . Optionally, a backwash pump 34 may be operated to flow permeate from a backwash tank 36 , with or without cleaning chemicals, through an opened backwash valve 38 , and to the train 16 . Other optional cleaning processes involve filling the tank 20 with a cleaning solution and soaking the membranes or permeating cleaning solution through the membranes. At some point in a cleaning or deconcentration cycle, a drain valve 32 may be opened to drain the tank 20 of accumulated solids or cleaning solutions. To refill the tank, the feed valve 28 is opened after the drain valve 32 is closed. During the refilling, the feed valve 28 may be opened to a predetermined partially open position to avoid filling the tank 20 too rapidly, which may damage the membranes. Once the tank is full, and the permeate FCV 30 is open, the feed valve 28 is left fully open.
[0013] The filtrate headers 18 of the trains 16 are connected to a common plant permeate pipe 40 . The plant permeate pipe 40 is in turn connected to the inlet of a permeate pump 42 . The permeate pump 42 discharges to a connecting pipe 44 . Although a single permeate pump 42 is shown in FIG. 1 , there would typically be a set of pumps connected in parallel to the plant permeate pipe 40 and all discharging to the connecting pipe 44 .
[0014] The permeate FCVs 30 are typically left fully open while a train 16 is producing permeate. The permeate FCVs 30 are not operated to produce the same flux from each train 16 . However, if a train 16 is exceeding its maximum permissible flux (which may be greater than its typical design flux) then the permeate FCV 30 is partially closed to prevent over-fluxing of that train 16 .
[0015] The permeate pump 42 creates a partial vacuum, which is shared across all of the trains 16 . The vacuum applied to the trains 16 will be generally equal between the trains 16 but for some variation due to different flows, and head losses, in the filtrate headers 18 . Since the vacuum is generally equal between trains 16 , the flow drawn from each train 16 will vary according to the permeability of the membranes in each train 16 , subject to dampening cause by variations in water level discussed earlier, and variations in head loss in the filtrate headers 18 .
[0016] The resulting variances in permeate flow between trains 16 is tolerated as long as none of the trains 16 exceed their maximum flux. This is more energy efficient than partially closing the permeate FCVs ( 30 ) to balance the trains 16 . If the flow variances result in a train 16 exceeding its maximum flux, the permeate FCV 30 can be closed by a pre-determined amount, or by an amount calculated or predicted to bring the train 16 back under its maximum flux. If a permeate FCV 30 is closed by a pre-determined amount, this adds resistance to the train 16 being over-fluxed, thus reducing its flux for the next permeate cycle. If the train 16 is still above the maximum permitted flux in the next permeate cycle, then the permeate FCV 30 is closed by another pre-determined amount.
[0017] To determine whether a train 16 is exceeding its maximum flux, a flow indicator-transmitter (FIT) can be placed in the filtrate header 18 . Alternatively, the flux can be estimated by measuring the rate of water level decrease in a tank 20 when the tank inlet 26 is closed and permeate continues. This can occur at the start of a deconcentration or cleaning sequence, or in a separate flux test. Alternatively, since the water level in the tanks 20 is related to flux through the trains 16 , a low water level in a tank 20 , or a large difference in water level between two or more tanks 20 , indicates a high flux in the train 16 in the tank 20 with a low water level. The water level of a tank 20 , or the difference in water level between a tank 20 and the average water level or another tank 20 , can be correlated to flux and used to indicate whether a train 16 is exceeding its maximum flux. In another alternative, flow in a train 16 is estimated by measuring the pressure in its associated tank inlet 26 or in all tank inlets 26 . The difference in pressure in a tank inlet 26 relative to the static head in the tank 20 can be correlated to the flow velocity, and flow rate, into the tank inlet 26 . Similarly, pressure in the tank inlet 26 less static head in the tank 20 can be compared between tanks 20 to determine if one train 16 is above its maximum permissible flux.
[0018] The permeate pump 42 discharges directly into the inlet of an RO feed pump 46 . Although only one RO feed pump 46 is shown, a set of RO feed pumps 46 connected in parallel is likely to be used. The permeate pump 42 acts as a booster pump delivering water to the RO feed pump 46 at a pressure at or above the specified minimum inlet pressure of the RO feed pump 46 , or at least sufficient to prevent cavitation in the RO feed pump 46 . For example, the permeate pump 42 may discharge water at a pressure of 125 kPa or more.
[0019] The RO feed pump 46 in turn delivers water at high pressure to a set of one or more RO units 48 . Each RO unit 48 may be, for example, a set of spiral would membrane elements arranged end to end in a pressure vessel. Optionally, the RO units 48 may be replaced with nanofiltration units or a combination of RO and nanofiltration units.
[0020] Permeate from the RO units 48 is collected in appropriate pipes and exits through a product water outlet 50 . On its way to the product water outlet 50 , the RO permeate passes through a permeate FIT 52 , typically a magnetic flowmeter, that measures the flow of RO permeate. The permeate FIT 52 is connected to a variable frequency drive (VFD) 60 that controls the speed of rotation of permeate pump 42 . Brine from the RO units 48 , also called rententate or reject water, is collected in appropriate pipes and exits through a brine FIT 56 . The brine FIT 56 is connected to a brine valve 58 . For both of the FITs 52 , 56 , their connection as shown in FIG. 1 and discussed above is intended to indicate the primary part of the system 10 controlled by each FIT 52 , 56 . The FITs 52 , 56 are also connected to appropriate controllers, for example a programmable logic controller (PLC) or computer, electrical circuitry and servos as required to operate the VFD 60 and brine valve 58 . A controller (not shown) may receives signals from both FITSs 52 , 56 and, optionally, other sensors in the system 10 and coordinates the control of multiple components in the system 10 .
[0021] In one example of a control scheme, a desired product water (RO permeate) flow rate and recovery rate are selected. A reject flow rate is calculated that will provide the selected recovery rate at the RO permeate flow rate. In a feedback control loop, the brine valve 58 is modulated based on signals from the brine FIT 56 as required to maintain the calculated flow through the brine outlet 54 . In another feedback control loop, the VFD 60 modulates the speed of permeate pump 42 as required to produce the desired RO permeate flow, as sensed by RO permeate FIT 52 . RO feed pump 46 generally runs at a constant velocity over extended periods of time, for example a day or more. However, RO feed pump 46 may be driven by a VFD and operate at various speeds. For example, the controller may be able to direct the RO feed pump 46 to operate at one of a set of available speeds. If the permeate pump 42 is unable to deliver the required flow, then the RO feed pump 46 may be instructed to operate at a higher speed. Conversely, if pressure at the inlet to the RO feed pump 46 falls below a minimum allowed pressure, the RO feed pump 46 may be instructed to operate at a lower speed. Dynamic adjustments to the RO permeate flow rate, for example over periods of time of one hour or less, are made by adjusting the speed of the permeate pump 42 . The permeate pump 42 preferably outputs water at a generally constant flow rate, although possibly with variations of up to 5% above or below a preselected flow rate.
[0022] Variations in the speed of the permeate pump 42 cause corresponding variations in the TMP applied to the UF trains 16 . As discussed above, permeate FCVs 30 are provided in the filtrate headers 18 . However, the permeate FCVs are not used to balance flows between trains or to ensure that any particular flow rate is produced from each train 16 . Instead, the permeate FCVs 30 remain fully open as long as a train 16 does not exceed its maximum flux. While a train 16 is isolated for a deconcentration or cleaning procedures, the TMP and flux of the remaining trains 16 increases. The total membrane surface area of the trains 16 is designed to allow at least one train 16 to be isolated without exceeding the maximum flux of all of the remaining trains 16 and to accommodate at least some irreversible fouling over the service life of the membranes. A train 16 typically exceeds its maximum flux only while another train 16 is isolated. The maximum flux may be larger than the typical design maximum flux of the same membranes, where the typical design maximum flux assumes continuous operation at that flux. However, if a train 16 chronically exceeds its maximum flux, that may indicate that one or more other trains 16 with lower flux may require replacement of some or all of its membrane modules or an intense recovery cleaning.
[0023] This written description uses examples to disclose the invention and also to enable any person skilled in the art to practice the invention, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the invention is defined by the claims, and may include other examples that occur to those skilled in the art. | A water treatment system combines a microfiltration or ultrafiltration membrane system with a downstream reverse osmosis membrane system. The MF or UF system has multiple trains of immersed membrane modules. The trains are connected to a common permeate pump. The permeate pump discharges directly into the inlet of an RO feed pump. The membrane trains are each subjected to the same suction. The permeate pumps are operated to provide the required flow to the RO feed pump at or above the minimum inlet pressure of the RO feed pump. | 2 |
This is a continuation-in-part of application Ser. No. 10/942,078 filed on Sep. 14, 2004, now U.S. Pat. No. 7,581,375, which is incorporated herein in its entirety by this reference
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to machines and methods for harvesting food crops, and more particularly, to improved small-scale machines and related methods for separating larger volumes of vine-borne crops from their vines while effectively removing unwanted dirt, vegetation and debris, minimizing damage to the fruit itself, and promoting better sorting of fruit.
2. Description of the Prior Art
Vine-borne crops have traditionally been harvested and processed by hand. However, such manual harvesting and processing was often tedious, time-consuming and expensive. Various machines, such as the one disclosed in U.S. Pat. No. 6,033,305, have been developed over the years to automate part, or all, of this process. These machines are able to harvest vine-borne crops from the ground at much faster speeds than humans. However, these machines were often inefficient in other aspects of the harvesting process. Early harvesting machines severed entire plants and dropped them upon the ground, with the desired crops remaining affixed to the plants. Then, collection devices would retrieve the mixture of vegetation, dirt and debris for processing. Human sorters would then be required to sort through the mixture to separate the crops from the rest, and extract the former. The human sorters had to quickly process these mixtures to prevent a backlog. As a result, some suitable crops were lost because they were too far entangled within the plants, or simply overlooked by the human sorters.
Various devices have been developed over the years to improve the mechanized harvesting process, and to minimize the need for human sorters. For example, U.S. Pat. Nos. 4,257,218, 4,335,570, and 6,257,978 all disclose harvesting machines utilizing at least one form of agitating device (such as vibrating shaker heads or conveyor belts) to dislodge tomatoes from the vines. Several harvesting machines, such as those disclosed in U.S. Pat. Nos. 6,257,978 and 6,033,305, also utilize forced air pressure systems to further remove dirt and debris.
Unfortunately, larger is not always better. While wider and larger machines are generally capable of harvesting and processing a higher volume of vine-borne crops, many road and/or field situations make it impossible or impractical to use or bring these large machines in to perform the desired harvesting. Such machines are also more difficult to maneuver. Such limited maneuverability may require the machine operator to spend additional time repositioning the machines to process each row of crops, or cause the machines to inadvertently trample one or more rows. In addition, larger machines tend to weigh more, and the added weight not only affects maneuverability (e.g. turning), it also makes the larger, heavier machines unusable in moist or muddy fields where they tend to bog down. It is therefore desirable to provide a smaller scale machine that is capable of harvesting larger volumes of vine-borne crops.
In addition, the design of many existing large and small-scale machines may cause damage to the fruit by imparting numerous drops and/or turns during processing. Many machines require the fruit to drop a distance of several feet over the course of processing through the machine, and to make several turns during the process. Each drop and each turn provides another point where the fruit may be damaged, so it is desirable to minimize the number and/distance that the fruit drops through the machine, and to minimize the number of turns the fruit makes as it travels through the machine.
Effective separating and sorting of harvested fruit is also important. More efficient removal of dirt, vegetation, trash and debris as well as more accurate sorting of fruit is possible when the harvested materials are uniformly dispersed, and not bunched together. An unfortunate side effect of machines in which the fruit makes multiple turns is that the fruit and associated trash and debris tends to bunch together. Rather than the fruits being evenly spaced upon the conveyors (so that they may be easily examined and processed), these corners cause the fruits to become crowded as they are transported onto an intersecting conveyor potentially forming windrows, making them more difficult to inspect and sort. This bunching makes removal of the trash and debris more difficult, and once removed, the bunching of the harvested fruit makes sorting more difficult as well. Furthermore, each turn involves a drop from one conveyor to another, risking additional damage to the fruit, and requiring more maintenance and cleanup from breakage. Transverse turns also tend to increase the overall width and size of the harvester machine. All of these consequences make it even more desirable to minimize the number of turns the fruit makes as it travels through the machine.
Blowers for cleaning trash and debris out of the fruit stream have been used in existing machines. Air from the blower is typically directed between two conveyors into the fruit stream as the fruit makes a ninety degree turn at the rear of the machine. The trash and debris is blown far enough to clear the receiving conveyor and drop off to the ground. It is therefore desirable to provide a machine with a blower unit that does not require the fruit to be subjected to the problems associated with unnecessary turns.
Suction units have also been used in existing harvesting machines for pulling the trash off the fruit stream on each side of the harvester, with the fan positioned in the typical application directly above a pickup point as fruit moves from one conveyor to another. This is not feasible for use on a small scale machine because of vertical space limitations of fitting a sufficiently large enough fan without lengthening the machine further or raising the height and creating shipping problems. The additional single conveyor width compounds the problem. It is therefore desirable to provide an effective suction system that may be used in a small scale machine.
It is therefore desirable to provide a small-scale vine-borne crop harvesting machine capable of processing a large volume of crops that is usable in a wide variety of field situations where larger machines cannot be used. It is further desirable that the harvesting machine effectively process vine-borne crops with minimum potential damage to the fruit. It is further desirable that the machine provide a minimum number of drops and turns so that the fruit is less susceptible to damage, so that trash and debris may be more effectively removed, and so that the fruit itself may be more efficiently sorted.
SUMMARY OF THE INVENTION
The present invention provides compact fruit-vine harvesters and separation systems in which the harvested fruit travels along a vertical plane or path during processing inside the machine, and makes only one ninety-degree turn following such processing in order to exit. The systems include machines and related methods for harvesting vine-borne crops. One embodiment of the machine is relatively compact, having a frame that is dimensioned such that its width is substantially the same as the wheel or track base so that it may travel on narrow roads, and be used in narrow field conditions. The machines provide for vine borne crops to be severed, separated, cleaned and machine-sorted along a single substantially vertical plane or straight (unturning) path inside the machine before making a single turn just prior to exit. Harvested fruit passing through the machines have fewer drops than seen in existing machines (typically two fewer drops). The machines incorporate a blower system, or a suction system, or a combination of blower and suction system for efficient removal of unwanted dirt, vegetation and debris.
In one embodiment, a severing device is provided at the forward end of a machine for severing fruit-laden vines from the ground. A first conveyor is provided that brings the severed fruit-laden vines to an upper position in the machine. It is preferred that this pre-processing (severing and depositing into the machine) be accomplished along the same vertical plane as the remaining processing inside the machine. However, multiple severing devices and/or multiple conveyors may be used to remove and deposit the vines into the machine that may not necessarily be oriented along the same vertical plane. In several embodiments, the severed fruit-laden vines cross an adjustable gap and are delivered onto a second conveyor, the gap allowing loose dirt and debris to fall through the machine to a dirt cross conveyor. In several embodiments, the material on this conveyor is passed through a vision system which ejects the red fruit back into the machine as the dirt and debris pass through to the ground. The fruit-laden vines are introduced into a rotating shaker having tines that engage and loosen the vines, causing the fruit to be dislodged as it shakes. The dislodged fruit drops onto a second conveyor below the shaker, and the vines are deposited onto a third conveyor. While traveling along the third conveyor, which is provided with large slots or as a wider pitch belted chain so that fruit can pass through, additional agitation may be imparted to the vines to dislodge any remaining fruit which falls through and is returned to the second conveyor. All of the conveyors are set up relatively close to each other so as to minimize the dropping distance of the fruit. These conveyors are all lined up substantially along the same vertical plane, so that the fruit and related materials are not turned and remain uniformly dispersed across the width of the conveyors.
Some dirt, debris, and vegetation may be deposited on the second conveyor along with the dislodged fruit. To remove this remaining trash, in several embodiments the second conveyor delivers the fruit and trash across an adjustable gap in which a strong upward air flow is provided through a nozzle attached to a blower below. The nozzle extends along the width of the second conveyor so that all fruit and trash is affected thereby. The airflow may be adjusted so that it is strong enough to blow away substantially all loose dirt, debris and vegetation without blowing away the fruit itself. The airflow also tends to remove trash and vegetation that may have become adhered to the second conveyor because of moisture or the like.
In some embodiments, an intake opening for a variable speed suction unit may be provided above the gap and blower nozzle to receive and remove all of the trash that is blown free by the lower nozzle. In other embodiments, one or more suction units are provided without any blower, preferably located along one or both sides of the fruit path, with special ducting to focus the suction over the fruit traveling through the machine along the vertical plane.
In some embodiments of the dual system using both blower and suction, one or more flaps are pivotally provided in the ducting for the blower system. Such flaps are activated when it is sensed that airflow has been affected by a large piece of vine engaged (clogged) in the suction system. When this condition is sensed, as, for example, a change in static pressure, a flap on the blower nozzle is moved so as to redirect the air flow forward in the machine and partially deadhead the blower, cutting off the airflow until the clog is cleared. This prevents trash that should be sucked up by the clogged suction unit from being blown all over the cleaned fruit on the conveyor. Once the clog is cleared, the normal condition is again sensed, and the flaps are returned to their original position(s) for normal operation.
In several embodiments, one or more continuously rotating rollers may be provided adjacent to the upper intake opening to dislodge any large pieces of vegetation or trash to prevent the upper opening from becoming clogged. Each roller itself is preferably smooth so that it does not become entangled with the vegetation or trash, but it may be provided with teeth, lagging, textured covering or tines to engage such materials if so desired. Each roller may rotate in either direction, so long as it tends to keep the vegetation and trash from clogging the intake opening of the upper suction unit.
The cleaned fruit that passes through the blower/suction gap is then deposited onto a fourth conveyor that is also in line with the three previous conveyors. The fourth conveyor takes the fruit to an automatic sorting unit which kicks out unwanted fruit according to its programmed instructions. Since the fruit has not traveled through any turns up to this point, it remains evenly separated on the fourth conveyor thereby improving the sorting process. Then, finally, the fruit makes its one and only turn where it is deposited onto a transversally oriented conveyor. Here, hand sorting may be performed, followed by deposit of the fruit onto a final conveyor which takes it up and out of the machine, usually for deposit into a waiting hopper alongside the machine. In an alternative embodiment, the transversally oriented conveyor and the final conveyor are one and the same, making the fruit available for sorting and then elevating it out of the machine to the hopper waiting alongside.
It is therefore a primary object of the present invention to provide a machine for harvesting vine-borne crops in which the harvested fruit travels along a substantially straight path within the machine as the fruit is separated from the vines, cleaned and sorted, prior to making a single turn followed by exit.
It is also an important object of the invention to provide a machine for harvesting vine-borne crops in which the harvested fruit travels a minimal distance from the uppermost to the lowermost point during processing, reducing the overall distance the fruit drops through the machine in order to reduce the potential for damage to the fruit.
It is also an important object of the invention to provide a machine for harvesting vine-borne crops in which the harvested fruit is uniformly dispersed as it is conveyed through the machine to facilitate better removal of unwanted trash and debris, and to facilitate better sorting of fruit.
It is also an important object of the invention to provide a machine for harvesting vine-borne crops in which unwanted dirt, vegetation and debris is removed through the action of an adjustable blower device provided along the path of travel through the machine.
It is also an important object of the invention to provide a machine for harvesting vine-borne crops in which unwanted dirt, vegetation and debris is removed through the action of adjustable suction device(s) provided along the path of travel through the machine.
It is also an important object of the invention to provide a machine for harvesting vine-borne crops in which unwanted dirt, vegetation and debris is removed through the dual action of an adjustable lower blower device and an adjustable upper suction device that are provided adjacent to each other along the path of travel through the machine.
It is also an important object of the invention to provide a small-scale machine for harvesting large volumes of vine-borne crops that may be deployed in vineyards and fields where larger machines cannot be efficiently used.
It is also an important object of the invention to provide improved methods for harvesting and processing vine-borne crops.
Additional objects of the invention will be apparent from the detailed descriptions and the claims herein.
DESCRIPTION OF THE DRAWINGS
FIG. 1 is a top view of an embodiment of the present invention.
FIG. 2 is a side view of an embodiment of the present invention along line 2 - 2 of FIG. 1 .
FIG. 3 is a rear view of an embodiment of the present invention along line 3 - 3 of FIG. 1 .
FIG. 4 is a cut away side view along line 4 - 4 of FIG. 1 illustrating major operative elements of flow paths through the invention.
FIG. 5 is a detailed cut away side view along line 5 - 5 of FIG. 1 of an exemplary air blower and air suction device of an embodiment of the present invention.
FIG. 6 is a side view along line 6 - 6 of FIG. 1 of an exemplary mechanical fruit sorter of an embodiment of the present invention.
FIG. 7 is a top view of a suction device of an embodiment of the present invention along line 7 - 7 of FIG. 2 .
FIG. 8 is a side view along line 8 - 8 of FIG. 16 of another embodiment of the present invention illustrating a blower for cleaning harvested crop.
FIG. 9 is a top view of the embodiment of FIG. 16 showing the cleaning elements.
FIG. 10 is a side view along line 10 - 10 of FIG. 17 of another embodiment of the present invention illustrating overhead suction for cleaning harvested crop.
FIG. 11 is an end view along line 11 - 11 of the embodiment of FIG. 16 .
FIG. 12 is a rear view along line 12 - 12 of FIG. 18 of another embodiment of the present invention illustrating dual suction fans for use in cleaning harvested crop.
FIG. 13 is a top view of the embodiment of FIG. 18 showing cleaning elements
FIG. 14 is a side view of an alternative embodiment of the present invention showing the blower and suction fan system operating under normal conditions.
FIG. 15 is a side view of the embodiment of FIG. 14 showing the blower and suction fan under a plugged/clogged state with the blower flap directing air forward in the machine.
FIG. 16 is a top view of an alternate embodiment of the present invention having a blower only.
FIG. 17 is a top view of an alternate embodiment of the present invention having a suction fan only.
FIG. 18 is a top view of an alternate embodiment of the present invention having dual suction fans.
DETAILED DESCRIPTION
Referring to the drawings wherein like reference numerals designate like or corresponding parts throughout the several views, and referring particularly to FIGS. 1 and 2 , it is seen that the illustrated exemplary embodiment of the invention is an apparatus and method for harvesting above-ground food plants grown in rows upon elongated planting ridges. The exterior components of the illustrated apparatus generally comprise a self-propelled vehicle body 10 having a driving compartment 11 , an adjustable arm 12 with a pickup device 14 and conveyor 15 , separator 20 , optional sorting platform 16 , and a discharging conveyor 17 .
As indicated in FIG. 2 , an adjustable arm 12 may be affixed to the front end of the vehicle body 10 . The adjustable arm 12 may be any number of commercially available devices that allow the operator to adjust the position of the arm 12 relative to the ground, said position depending upon the characteristics of the particular crop harvested or its environment. A gage wheel 13 for height adjustment may be mounted at the front end of the adjustable arm 12 . The pickup device 14 may be any commercially available device capable of severing tomato vines V at or near ground level, such as a cutting disc or plurality of opposing blades, and a lift for placing the severed vines onto conveyor 15 . The pickup conveyor 15 may be an endless longitudinal conveyor belt traveling in a rearward direction into the separator 20 . Sorting platform 16 may be affixed to the rear end of the vehicle body 10 . Platform 16 allows one or more humans to examine and hand sort the tomatoes T on conveyor 26 before they are passed along to a discharging conveyor such as 17 . Conveyor 17 is depicted in the rear view of FIG. 3 in its retracted position, with phantom lines showing its extended position over a receiving hopper 70 in an adjacent row.
FIG. 4 depicts the internal operation of one embodiment of the separator 20 of the present invention viewed from the right side. In this embodiment, an endless motor-driven longitudinal receiving conveyor 19 is adapted to receive the tomato vines V from the exterior pickup conveyor 15 and travel toward the rear end of the vehicle body 10 . An adjustable gap 18 is provided between the pickup conveyor 15 and receiving conveyor 19 , said gap 18 allowing loose tomatoes T, dirt clods and other debris to drop from the vines V while said vines travel between the two conveyors 15 and 19 . It is to be appreciated that the width of gap 18 may be varied to account for different sizes of vines V, tomatoes T, dirt clods and debris. For example, gap 18 may be set at a sufficiently small size that only the smaller dirt clods and debris fall through, or at a sufficiently large size that larger objects including small loose tomatoes T may also fall through.
In some embodiments, an endless transversely oriented motor-driven debris conveyor 21 , having one end underneath gap 18 and the opposite end extending outside the vehicle body 10 , may be positioned to receive the loose tomatoes T, dirt clods and debris falling through gap 18 . A commercially available sorting mechanism 27 may be mounted in close proximity to the debris conveyor 21 to recognize loose tomatoes T thereon, and place them onto the endless motor-driven collection conveyor 29 mounted under conveyor 21 . The remaining dirt clods and debris fall off conveyor 21 and outside the vehicle body 10 . Tomatoes T are collected on 29 and conveyed back up on to the machine and deposited onto an endless motor-driven longitudinal first processing conveyor 22 . Alternatively, if gap 18 is set at a sufficient size to allow only dirt clods and debris to fall through, the debris conveyor 21 may transport all objects falling through the gap 18 to the outside of the vehicle body 10 .
A shaker brush 30 is positioned for receiving tomatoes and vines from processing conveyor 19 . Said shaker brush 30 may be any commercially available brush comprising a plurality of tines 31 and an agitating mechanism (not depicted) for concurrently rotating and vibrating the shaker brush 30 , such as an eccentric weight assembly or vibrating motor. It is rotatable along a central axis in a downward direction, causing the vines V to be pulled underneath the shaker brush 30 toward the rear end of the vehicle body 10 . The vibratory force of the shaker brush 30 is sufficient to dislodge tomatoes T from their vines V, along with most remaining dirt clods and debris, without excessively damaging the tomatoes T. The dislodged tomatoes T, dirt clods and debris are dropped onto the first processing conveyor 22 , while the vines V are deposited upon the recovery conveyor 23 .
Processing conveyors 22 and 29 (described below) are made up of segments which provide a plurality of openings or slots that are of sufficient size to support tomatoes T, but allow small pieces of dirt, vegetation and debris to fall through. Larger pieces are removed by blower 40 and suction device 60 described below.
The illustrated exemplary recovery conveyor 23 is an endless motor-driven longitudinal conveyor traveling toward the rear end of vehicle body 10 . Conveyor 23 is made up of segments which provide a plurality of openings or slots that are of sufficient size to allow tomatoes to fall through. An agitating mechanism (not depicted) may be provided in communication with the recovery conveyor 23 . Said agitating mechanism may be any commercially available device for agitating the tomatoes and vines on the recovery conveyor 23 . The agitator should be capable of providing loosening vibratory motions to further separate the tomatoes T that remain entangled but not connected with the vines V at this stage. A recovery shelf track 24 is positioned underneath the return segment of the recovery conveyor 23 to capture the tomatoes T falling through the slots of the recovery conveyor 23 , and, in conjunction with the return movement of the recovery conveyor 23 , transport the tomatoes T to the first processing conveyor 22 .
The illustrated exemplary second processing conveyor 25 is an endless motor-driven longitudinal conveyor belt traveling toward the rear end of vehicle body 10 . Conveyor 25 is positioned near the rear end of first processing conveyor 22 . There is an adjustable gap 28 between the first processing conveyor 22 and the second processing conveyor 25 . In some embodiments, an air blower 40 is mounted below the front end of the second processing conveyor 25 , with the nozzle 43 directed toward the gap 28 between the two conveyors, so that the forced air pressure emitted from the nozzle 43 contacts the tomatoes T, vegetation, dirt and debris falling from the first processing conveyor 22 onto the second processing conveyor 25 . Such forced air pressure may be varied so that it is of sufficient strength to separate vegetation, dirt and debris from the tomatoes T, and force said materials upward and towards the rear without blowing the tomatoes themselves away. In some embodiments, nozzle 43 may be provided with a narrow slit opening 42 to focus the flow of air as shown in FIG. 9 . Optional roller(s) 45 may be used to help with the separation of blowing materials by rotating counterclockwise and direct the said materials towards the collection conveyor 72 . The vegetation, dirt, and debris may be collected on a transverse conveyor 72 mounted behind roller(s) 45 and directly above conveyor 25 . The collected dirt and debris are directed off the side of the machine falling to the ground.
In some embodiments, an air suction device 60 , such as a fan or vacuum, is positioned above the gap 28 , as shown in FIG. 10 . The size and shape of the vacuum opening 63 may be varied, as discussed below, to assure that equal air suction (vacuum) is provided across the entire path (width) of conveyor 22 and gap 28 . The vacuum imparted by this suction device 60 may be varied so that it is of sufficient strength to capture the dirt, vegetation and debris.
In one embodiment, the suction fan 60 is positioned vertically on the side, with ducting to connect the pickup nozzle area to the inlet of the fan. (See FIG. 7 .) The additional width of the conveyor is an additional challenge for the fan. To overcome this, a larger unit drawing even more power may be used. In alternative embodiments, dual fans 60 may be provided, one on each side of the fruit path, with ducting allowing the entire fruit path to be subject to suction, as shown in FIGS. 12 , 13 and 18 .
FIG. 5 provides a detailed side view of an embodiment using both the air blower 40 and air suction device 60 of the present invention. As shown therein, the nozzle 43 of the air blower 40 is positioned in close proximity to and across the width of gap 28 between the first processing conveyor 22 and second processing conveyer 25 , so that the forced air pressure emitted through nozzle 43 contacts the tomatoes T, dirt clods and debris falling from the first conveyor 22 to the second 25 . The suction device 60 is positioned above the gap 28 with its opening 63 directly across from the nozzle 43 , so that the forced air pressure emitted from the nozzle 43 (and the dirt, vegetation and debris carried by such pressure) is directly received by the opening 63 of the suction device 60 . The volume of air provided by the blower and/or suction should generally be adjusted as high as possible without being so strong as to remove the tomatoes themselves.
Blower 40 also provides the additional function of dislodging vegetation or debris that may have become adhered to conveyor 22 through moisture or the like, thereby improving the efficiency and operational functionality of conveyor 22 . It is to be appreciated that in other embodiments, blower 40 may be provided without suction 60 (see FIGS. 8 , 9 , 11 and 16 ), and in other embodiments suction 60 may be provided without blower 40 (see FIGS. 10 and 17 ).
In some embodiments, at least one roller 45 is provided. Roller(s) 45 may be provided adjacent to and below the opening 63 of suction device 60 ( FIG. 5 ), or above the nozzle 43 of the blower device ( FIG. 9 ), and extending across the width of opening 63 or nozzle 43 . Roller(s) 45 may have a smooth surface, or may be provided with teeth, lagging or tines of appropriate length to engage the vegetation and other dislodged debris. In the suction embodiments of the present invention, roller(s) 45 rotate while the suction device 60 is operating so as to make contact with and dislodge any excessive vegetation or other debris in order to prevent opening 63 from being clogged. As shown in FIG. 5 , roller(s) 45 may be rotated in a clockwise direction so as to continuously be causing vegetation and debris to be pushed out and away from opening 63 . However, this may cause such vegetation and debris to be deposited with the relatively clean tomatoes T on conveyor 25 . Thus, in many circumstances, it may be more beneficial for one or more of rollers 45 to rotate counter-clockwise so as to force the vegetation and debris into opening 63 so that it may be carried away. Among other things, the size and moisture content of the vegetation and debris may dictate whether roller(s) 45 operate in a clockwise or counter-clockwise direction, or some rollers in one direction and others in the opposite direction.
FIGS. 8 and 9 illustrate an embodiment of a blower used on the small scale machine. On the side view of FIG. 8 , a blower outlet 43 is positioned to direct air upward through the gap 28 between two conveyors 22 and 25 . The air goes through the fruit stream, lifting the lighter trash upward into the air chamber and over optional roller(s) 45 . In this embodiment, roller(s) 45 help deliver debris onto a cross conveyor 72 where it may be transferred into an optional removal chute 75 . On the backside of the roller 45 , the air is allowed to vent out one side in a larger cavity with a conveyor underneath. Part of the trash in the air settles out and is conveyed to the side of the machine with the conveyor 72 . The lighter trash will likely stay airborne and vent out with the air to the side. In some embodiments, the air may be vented off both sides, with the conveyor split to run both directions. In another embodiment, air may also be allowed to vent towards the rear of the machine through a screen. In this embodiment, when the system stops at the end of the field, the air-stream would stop, and the loose trash collected on this screen would fall down to the conveyor.
In some embodiments, accommodation for trash collection and directing material to the ground with a flexible chute 75 (see FIG. 11 ) made with flaps may be needed to prevent light trash from collecting in the wrong places and causing engine or hydraulic overheating. The trash conveyor 72 is preferably a flat belt, not a belted chain. On FIG. 8 , the sides of the air chamber are enclosed to direct the trash over roller 45 to the collection conveyor. The underside of the recovery shelf track 24 serves as the top of the air chamber.
A side view of a suction device 60 is shown in FIG. 5 , and a top view is shown in FIG. 7 . In this illustrated embodiment, suction device 60 includes a variable speed fan or blower unit 61 attached to a channel 62 that is attached, in turn, to a duct 64 leading to opening 63 . An exhaust duct 65 may also be provided. Because of the change in direction of airflow through channel 62 and duct 64 , the size and shape of opening 63 may be varied so as to provide a uniform level of suction across the entire path of conveyor 25 and gap 28 . By way of example and without limitation, opening 63 may not be provided in a rectangular form, but the left side of opening 63 may be narrower than the right side so as to assure level airflow across its length.
In an alternative to the embodiments using both suction 60 and blower 40 , one or more flaps 76 may be provided on the blower outlet nozzle 43 which may be opened or closed to respond to clogging of the suction system by a large clump of vine mass. See FIGS. 14 and 15 . Such a clog causes the suction 60 to lose some of its airflow, and when used with blower 40 , may result in undesirable redirecting of blower air flow blowing trash where it is not wanted. The flap 76 is attached to one or more electronically controlled solenoids or other switches 77 , and a sensor 78 such as a static air pressure sensor is provided adjacent to the suction unit. If the sensor 78 detects a change in air pressure brought about by a clog caused by a large vine mass ( FIG. 15 ), the switches 77 are activated closing the flap 76 so as to redirect the air from the suction system forward in the machine into conveyor 22 , until the clog has cleared. See upward arrow of FIG. 15 . The clearing of the clog is sensed by the pressure returning to normal, at which point the switches 77 are deactivated returning the flaps to their normal operating positions, as shown in FIG. 14 .
FIGS. 12 , 13 and 18 illustrate an alternative embodiment using a dual suction fan arrangement. The top view of FIG. 13 shows ducting to both sides of the machine with no dividing partition inside the ductwork. Air is allowed to flow freely through with no catch point for trash to hook on. A very large volume of air can be moved with this embodiment without needing the additional space required for a single overly sized unit. The horsepower required to drive this embodiment is significant, but all the trash collected may be controlled.
It is to be appreciated that all of conveyors 15 , 19 , 22 , 23 and 25 are provided along the same vertical plane, and are operatively positioned, as described herein, above and/or below each other in this plane. In this way, the tomatoes T removed from the vines travel along a straight path, moving from, the front toward the rear of the machine, being directed by the conveyors and by gravity. This configuration avoids any left or right turns in the path that the tomatoes T travel through the machine, resulting in better distribution of the tomatoes across conveyor 25 when they reach the sorting stage. Left and right turns in the paths of other machine cause the tomatoes to roll together into windrows that are more difficult to separate and sort.
In some embodiments, an endless motor-driven transversely oriented output conveyor 26 may be positioned near the rear end of the second processing conveyor 25 . A gap is provided between the second processing conveyor 25 and the output conveyor 26 . An optical/mechanical fruit sorter 50 is mounted in close proximity to this gap. The optical/mechanical fruit sorter 50 may be any commercially device capable of selecting or rejecting tomatoes T based upon certain predetermined criteria, such as color. It should also comprise a means of sorting tomatoes T based upon their satisfaction of the predetermined criteria, such as a mechanical arm or pivoting gates. It is to be understood that the mechanical fruit sorter 50 may be replaced by, or supplemented with, human sorters who can manually examine the tomatoes on conveyor 26 as they stand on platform 16 .
Regardless of the particular examination method utilized, tomatoes T satisfying the predetermined criteria are transported to output conveyor 26 , while rejected tomatoes are removed therefrom, either by the mechanical sorter 50 or human sorters. The output conveyor 26 is in communication with the discharging conveyor 17 , which transports the satisfactory tomatoes from the present invention onto any number of commercially available hoppers, such as a trailer or truck bed 70 .
FIG. 6 depicts an embodiment utilizing a mechanical fruit sorter 50 located along the same vertical plane. It is seen that the mechanical fruit sorter 50 comprises a sensor 51 and pivoting gate 52 . The sensor 51 may be any commercially available device capable of determining whether the tomato T satisfies the predetermined criteria inputted by the operator. Tomatoes T satisfying such criteria are permitted to fall toward output conveyor 26 . As to tomatoes T 1 failing such criteria, the fruit sorter 50 causes the gate 52 to pivot outward, causing the failing tomatoes T 1 to miss the output conveyor 26 and fall outside the vehicle body 10 .
The use of a particular embodiment of the present invention will now be described without limiting the claims herein. In this exemplary embodiment, the operator inputs a series of predetermined criteria into the mechanical fruit sorter 50 , which defines the parameters for the ‘acceptable’ tomatoes harvested. The size of gap 18 is selected and set. The initial airflow for blower 40 and/or suction 60 is also selected (depending upon whether one or both is provided), although these may be changed during processing to provide appropriate removal of debris. The exemplary invention is then positioned before a row of tomato vines V. The adjustable arm 12 is placed in such a manner that the cutting device 14 will sever the tomato vines V at or near ground level. As the present invention proceeds along the row of tomato vines V, cutting device 14 severs the tomato vines V. The pickup mechanism receives the severed tomato vines V (along with loose tomatoes T, dirt clods and debris), and places them onto the pickup conveyor 15 . The pickup conveyor 15 then transports the vines V rearward into separator 20 .
The tomato vines V are transported over the gap 18 between the pickup conveyor 15 and receiving conveyor 19 . As they cross the gap, loose tomatoes T, dirt clods and debris smaller than the width of the gap fall through, and onto the debris conveyor 21 . The debris conveyor 21 passes the mixture through a sorting mechanism. Tomatoes T within the mixture are diverted to the collection conveyor 29 , then dropped onto the first processing conveyor 22 , while the dirt clods and debris passing through the sorting mechanism are discarded outside the vehicle body 10 .
The tomato vines V upon the receiving conveyor 19 travel along a vertical plane and contact the shaker brush 30 . As the downward rotation of the shaker brush 30 pulls the tomato vines V underneath the brush, the vibration of the brush tines 31 dislodges the tomatoes T from the vines V, along with the remaining dirt clods and debris. The dislodged tomatoes T, dirt clods and debris fall onto the first processing conveyor 22 , while the vines V (along with any tomatoes T still lodged therein) are deposited by the shaker brush 30 upon the recovery conveyor 23 .
As the recovery conveyor 23 transports the vines V along the vertical plane toward the rear of the vehicle body 10 , it is vibrated by an agitating mechanism. The vibrating motion of said mechanism is sufficient to dislodge the remaining tomatoes T from the vines V. These tomatoes T fall through the slots of the recovery conveyor 23 onto the recovery shelf track 24 . The vines continue rearward until they are ejected from the rear end of the vehicle body 10 . The return direction of the recovery conveyor 23 receives the tomatoes T and deposits them upon the first processing conveyor 22 , along with the tomatoes T dislodged by the shaker brush 30 .
The first processing conveyor 22 continues to transport the tomatoes T (and remaining dirt clods and debris) toward the rear end of the vehicle body 10 along the vertical plane. When the mixture reaches the rear end of the first processing conveyor 22 , it falls to the second processing conveyor 25 along the plane. During the fall, the mixture is struck by air pressure from the air blower 40 (if provided) mounted underneath the second processing conveyor 25 . The air should be of sufficient volume to cause the tomatoes to “dance,” that is, to be moved slightly so that the debris and vegetation around them is removed, while the tomatoes themselves are not. Such air pressure causes the dirt and debris to separate from the tomatoes T and fly upward, where they are captured by suction pressure from the air suction device 60 (if provided). The suction device 60 ejects the dirt clods and debris from the rear end of the vehicle body 10 , while the tomatoes T continue along the second processing conveyor 25 .
As the tomatoes T reach the rear end of the second processing conveyor 25 , they are analyzed by a mechanical fruit sorter 50 along the vertical plane. Tomatoes T satisfying the particular criteria previously inputted by the operator are transported onto output conveyor 26 , while unacceptable tomatoes are discarded out the bottom of the vehicle body 10 . The output conveyor 26 transports the acceptable tomatoes T past manual sorters standing on platform 16 , and then to the discharging conveyor 17 , where the tomatoes T are placed into transport hoppers 70 .
It is to be understood that variations and modifications of the present invention may be made without departing from the scope thereof, including different combinations of the various elements identified herein regardless of whether such combinations have been specifically described or illustrated. It is also to be understood that the present invention is not to be limited by the specific embodiments disclosed herein, but only in accordance with the appended claims when read in light of the foregoing specification. | The present invention is a compact fruit-vine harvester and separation system in which the harvested fruit travels along a vertical plane inside the harvester during processing, followed by a single turn for output. The system includes a machine and related methods for harvesting vine-borne crops. The machine provides for vine borne crops to be severed, separated, cleaned and machine-sorted along a straight path before making a single turn prior to exit. The machine incorporates a blower and/or suction system for efficient removal of unwanted dirt, vegetation and debris, and an optional roller to prevent clogging of the suction system. | 0 |
RELATED APPLICATION DATA
This application is a continuation of U.S. patent application Ser. No. 12/534,878, filed on Aug. 4, 2009, and titled “Handheld Low-Level Laser Therapy Apparatus,” which is incorporated herein by reference.
FIELD OF THE INVENTION
The present invention relates generally to a handheld low energy laser device for treating people and animals.
BACKGROUND OF THE INVENTION
The use of light for treating people and animals is well known. Since the early history of mankind people have used the light, from the sun to help cure ailments. In the mid 20Th century attempts were made to use concentrated light for treating wounded soldiers in World War II. In later years, the laser, which is based on the quantum phenomenon of stimulated emission, provided an excellent source of concentrated light for treating patients. The laser allows the use of a selected intensity of a monochromatic, and essentially coherent. This has been found to be effective in treating people for various ailments.
The use of a carefully selected wavelength, coherently directed toward a person provides energy for selectively stimulating processes in-living cells. This can help increase blood flow; excite cell activity and intensify inter-cell communications. Laser light treatments have been applied to various ailments such as:
a. Various skeletal and tissue pains and injuries:
1. Rheumatic and/or chronic joint inflammation; 2. Sport injuries, wounds, and fresh scars; 3. Lower and upper back pain; neck pains: 4. Plantar fasciitis and sprains; 5. Tennis elbow; 6. Achilles tendon infection; 7. Carpal tunnel syndrome: 8. Lymphedema—Edema;
b. Medical dermatology:
1. Acne; 2. Burns; 3. Scars; 4. Hemorrhoids; 5. Vitiligo (e.g. discolored skin); 6. Herpes simplex;
c. Aesthetics:
1. Aging and dermatolysis of the face; 2. Wrinkles; 3. Sensitive skin; 4. Post pregnancy stretch marks;
d. dental applications;
e. veterinary applications;
f. Acupuncture treatments;
and other applications.
The use of laser light in therapy has been shown to reduce pain, induce anti-inflammatory activity, induce healing processes and induce skin reuvenation.
In the past light therapy has been applied by large, expensive and hazardous equipment which requires application by trained personnel. Thus miniature, user safelaser therapy devices, which can be used at home, are desirous.
SUMMARY OF THE INVENTION
An aspect of an embodiment of the invention, relates to an apparatus and method for treating people using a handheld low level laser therapy device. The device includes a laser diode that provides a monochromatic single phased laser beam that disperses with a small angle (e.g. between 5-7 degrees) in one direction) and with a larger angle (e.g. between 30-40 degrees) in the direction perpendicular to the first direction. The device exploits the natural divergence of the laser diode to produce a light beam that illuminate a larger area simultaneously with a monochromatic, essentially coherent and collimated light beam.
The device includes a lens that turns the laser beam into a collimated beam wherein the rays from the smaller dispersion angle provides a narrow illumination area and the rays from the larger dispersion angle provide an elongated illumination area. Optionally, the elongated illumination area is at least twice the size of the narrow illumination area. In some embodiments of the invention the illumination area forms a rectangular area. Alternatively, the illumination area is an ellipsoidal area. Optionally, the beam provides eye safety as a result of the dispersion, which provides less intensity per unit area.
In some embodiments of the invention, the monochromatic laser beam is an invisible infrared beam. Optionally, the wavelength of the laser beam is between 800 to 900 nm. In an exemplary embodiment of the invention, a visible light source (e.g. a LED) is used to provide a supplementary visible light beam to accompany the invisible light beam so that a user will be able to see that the device is active and will not point the device toward his eyes. In some embodiments of the invention, the visible light beam coincides with the invisible laser beam. Alternatively, the visible light beam illuminates an area that surrounds the laser beam forming a frame around the invisible laser beam to enhance user safety.
In some embodiments of the invention, the device is activated by an eye safely mechanism that is activated by pressing the light emitting end against the target that is to be illuminated, to prevent a user from shining the laser beam without precaution. Alternatively, or additionally, other activation switches are available on the device.
In some embodiments of the invention, the laser diode is activated non-continuously when the device is activated, for example with a duty cycle of 50% or less. Optionally, the output power of the laser diode is continuously controlled by a servo loop that monitors the output of the laser diode and updates its duty cycle to maintain a constant power output by the laser beam, for example the pulse length or the frequency of turning on the laser diode are updated responsive to the detected intensity.
There is thus provided according to an exemplary embodiment of the invention, a laser therapy device, comprising:
a laser diode that is adapted to produce a monochromatic laser beam;
a lens that is adapted to receive the beam directly from the laser diode and exploit the natural divergence of the laser diode to form an essentially coherent monochromatic, collimated beam; wherein the formed beam is adapted to form on a plane perpendicular to the direction of propagation of the beam an elongated illuminated area in which the length of the illuminated area is at least twice the size of the width of the illuminated area:
a controller that is adapted to control activation of the laser diode; and
an encasement enclosing the laser diode, the lens and the controller; wherein the encasement is adapted to be hand held by the user.
In some embodiments of the invention, the lens is a toroidal lens having a different lens radius in the direction producing the length of the illuminated area and the direction producing the width of the illuminated area. Optionally, the beam produced by the laser diode is an infrared laser beam.
In an exemplary embodiment of the invention, the laser therapy device includes a visible light source that produces a visible light beam that is combined with the laser beam to provide a visible light as an indication of the presence of the invisible laser beam. Optionally, the visible light source is mounted, so that the image of the light source is in the focal plane of the lens. In an exemplary embodiment of the invention, the visible light beam is adapted to surround the invisible laser beam forming a frame enclosing the invisible light beam.
In an exemplary embodiment of the invention, the controller is adapted to control the duty cycle of the laser diode. Optionally, the controller is adapted to update the duty cycle of the laser diode to maintain a constant power output although the intensity of the laser diode changes over time. In an exemplary embodiment of the invention, the duty cycle of the beam produced by the laser diode is initially less than 50%. Optionally, the device includes a safety mechanism that activates the device by pressing the device against the illuminated object. In an exemplary embodiment of the invention, the illuminated area forms a rectangular or ellipsoidal shaped area. Optionally, the beam formed is an eye safe beam.
There is further provided according to an exemplary embodiment of the invention, a laser therapy device, comprising:
a laser diode that is adapted to produce a monochromatic laser beam;
a lens that is adapted to receive the beam from the laser diode;
a controller that is adapted to control the duty cycle of the laser diode and maintain a constant power output; and
an encasement enclosing the laser diode, the lens and the controller; wherein the encasement is adapted to be hand held by the user.
There is further provided according to an exemplary embodiment of the invention, a laser therapy device, comprising:
a laser diode that is adapted to produce a monochromatic laser beam;
a lens that is adapted to receive the beam from the laser diode:
a controller that is adapted to control activation of the laser diode;
an encasement enclosing the laser diode, the lens and the controller; wherein the encasement is adapted to be hand held by the user; and wherein the device is activated by a safety mechanism by pressiug the device against the illuminated object.
There is further provided according to an exemplary embodiment of the invention, a laser therapy device, comprising:
a laser diode that is adapted to produce a monochromatic laser beam;
a visible light source that is adapted to provide a light beam that surrounds the beam formed by the laser diode, forming a frame around the illumination pattern formed by the laser beam;
a lens that is adapted to receive the beam from the laser diode;
a controller that is adapted to control activation of the laser diode;
an encasement enclosing the laser diode, the lens and the controller; wherein the encasement is adapted to be hand held by the user.
BRIEF DESCRIPTION OF THE DRAWINGS
The present invention will be understood and better appreciated from the following detailed description taken in conjunction with the drawings. Identical structures, elements or parts, which appear in more than one figure, are generally labeled with the same or similar number in all the figures in which they appear, wherein:
FIG. 1 is a schematic illustration of a handheld low-level laser therapy (LLLT) device for performing laser therapy, according to an exemplary embodiment of the invention;
FIG. 2 is a schematic illustration of an internal structure for manufacturing a low-level laser therapy device that demonstrates the use of the natural divergence of the laser diode and lens configuration, according to an exemplary embodiment of the invention;
FIG. 3 is a schematic illustration of an internal structure for manufacturing a low-level laser therapy device with a safety activation mechanism, according to an exemplary embodiment of the invention;
FIG. 4 is a schematic illustration of an internal structure for manufacturing a low-level laser therapy device with a combination mechanism to superimpose visible light beam over laser beam, according to an exemplary embodiment of the invention; and
FIG. 5 is a flow diagram of a method of controlling the duty cycle of a laser diode, according to an exemplary embodiment of the invention.
DETAILED DESCRIPTION
FIG. 1 is a schematic illustration of a handheld low-level laser therapy (LLLT) device 100 for performing laser therapy, according to an exemplary embodiment of the invention. In an exemplary embodiment of the invention, device 100 provides as output an elongated monochromatic coherent laser beam 170 that is collimated by a lens directly from the natural divergence of a laser diode embedded in device 100 . In contrast to prior art devices, instead of focusing the laser beam from the laser diode to a single spot to have a stronger illumination on a single spot, the natural tendency of the laser diode is exploited to form an elongated beam to cover a larger area. The standard laser diode typically has a divergence of about 5-7 degrees along its width and about 30 to 40 degrees along its length. Instead of using a lens to correct the beam to a narrow beam, device 100 uses a lens to form a collimated elongated beam to cover a larger area, for example an area of 3-6 cm by 0.5 to 1 cm. In an exemplary embodiment of the invention, the length of the illuminated area is at least twice the width of the illuminated area. In an exemplary embodiment of the invention, the resulting elongated beam is essentially coherent having a light beam with an essentially common phase as accepted for laser diode emission.
Optionally, by illuminating a large area each point is illuminated with a weaker and safer laser beam, for example an eye safe beam, having an intensity, which is not hazardous to a persons eye. More power can be delivered more accurately to a specific area by illuminating for a longer time or increasing the intensity of the laser diode without moving device 100 . In contrast in a single spot laser a single point is illuminated intensely and an area is processed by moving the beam across the user's skin and illuminating each point.
In an exemplary embodiment of the invention, the light sources and electronic circuitry for powering device 100 are encased in an ergonomic encasement 110 designed to fit into a user's hand. Optionally, device 100 includes an on/off switch 125 , which turns device 100 on and off. When device 100 is in the on state—it may be activated by pressing on an activation switch 130 located on the side of encasement 110 . Alternatively or additionally, device 100 may be activated by pushing eye safety activation switches 105 against the person or object being radiated, when using device 100 . Activation when pressing against the person being radiated increase the safety of device 100 since it will not accidentally allow a user to shine light into the user's eye. In some cases pressing against the user's skin is advantageous since it may reduce blood flow and enhance efficiency of the light absorption. Alternatively, in some cases the user may have a wound and it is preferable to not press against the user's skin.
In some embodiments of the invention, device 100 is powered by an internal power source (e.g. batteries 135 ). Alternatively or additionally, device 100 can be powered by an external power source via a power-cable (not shown) that is plugged into an external power source, such as a household power socket. Optionally, when the device is plugged into an external power source the batteries may be recharged.
In some embodiments of the invention, device 100 includes a display 115 , for example an LCD display, which shows various information, such as the status of the battery, and/or a timer/counter. In an exemplary embodiment of the invention, the timer on display 115 is set by the user to a pre-selected value using a selector 120 , the value may represent an amount of time in seconds during which the device will remain active when activated by the user. The device will count down and deactivate the device automatically once it counts the pre-selected amount of time. For example if the user whistles to illuminate an area for a specific amount of time, he sets the timer with the desired amount of time and activates device 100 . Device 100 will illuminate the area until the time runs out.
FIG. 2 is a schematic illustration of an internal structure for manufacturing device 100 that demonstrates the natural divergence of the laser diode and lens configuration, according to an exemplary embodiment of the invention. In an exemplary embodiment of the invention, a laser diode 210 is mounted onto a base 230 . In an exemplary embodiment of the invention, laser diode 210 is selected to emit infra-red radiation with a monochromatic wave length between 800-900 nm and a power output of at least 100 mw, so that it will be effective in healing the user. Optionally, the wavelength is selected to have optimal performance in providing power to the biological cells of the user, thus it is possible that other wavelengths may be used (e.g. visible light or ultra-violet light) if found to be more effective in dealing with a specific ailment. Additionally, laser diode 210 may be selected having a stronger or weaker power output.
In an exemplary embodiment of the invention, the light from laser diode 210 disperses with a small angle 260 in one direction, and with a larger angle 250 in the perpendicular direction. Optionally, a lens 220 is placed opposite laser diode 210 to make use of the natural divergence of the laser beam produced by laser diode 210 by collimating the dispersing laser beam and forming an illumination of the elongated monochromatic coherent laser beam 170 on the skin of the user.
In an exemplary embodiment of the invention, lens 220 is a toroidal lens having a different lens radius in two directions, so that the diverging beam formed from laser diode 210 will extend perpendicular to the lens and form an elongated illumination from monochromatic coherent laser beam 170 . In some embodiments of the invention, lens 210 has a rectangular or ellipsoidal shape and creates a rectangular or ellipsoidal illumination. Alternatively or additionally, lens 210 may be a single lens, a double lens or any other combination of lenses as long as it produces the elongated monochromatic coherent laser beam 170 to radiate the user. Optionally, elements other than lenses may affect the unity of phase and direction of the coherent laser beam 170 .
FIG. 3 is a schematic illustration of an internal structure for manufacturing device 100 with an eye safety activation mechanism 300 , according to an exemplary embodiment of the invention. As mentioned above, in an exemplary embodiment of the invention, when device 100 is turned on, it can be activated by pressing the eye safety activation switch 105 against the body of the user. Optionally, eye safety activation switch 105 is connected to two sliders 310 and 2 springs 330 are inserted on the sliders one for each side. When eye safety activation switch 105 is pushed into encasement 110 sliders 310 are move inward and depress on two micro-switches 320 that instruct controller 240 to activate laser diode 210 . The use of eye safety activation switch 105 prevents the user from activating laser diode 210 and aiming it toward his eyes or the eyes of another person.
FIG. 4 is a schematic illustration of an internal structure for manufacturing device 100 with a combination mechanism to superimpose visible light beam 160 over laser beam 170 , according to an exemplary embodiment of the invention. In an exemplary embodiment of the invention, a visible light source— 410 (e.g. a LED) is mounted on a structure 430 above laser diode 210 to provide a visible light source. Optionally, structure 430 includes a polished back surface 420 (e.g. a mirror) to reflect the visible light towards lens 220 , so that it will be superimposed over the light rays originating from laser diode 210 . In some embodiments of the invention, only specific areas on the back surface are polished to control the resulting geometry of the visible light beam. In an exemplary embodiment of the invention, a cross section of the resulting beam includes an inner area formed by laser beam 170 and a larger area formed by visible light beam 160 that surrounds the inner area and provides a visible border around it, so that the user knows where the invisible laser beam is located.
Optionally, the visible light beam 160 serves as a safety measure, by providing the user with an indication that the invisible laser beam 170 is also there and may be dangerous if aimed at a person's eye.
LED 410 is preferably mounted, so that the image of the light source is in the focus of lens 220 .
In an exemplary embodiment of the invention, laser diode 210 is operated in short pulses at a constant frequency, for example of 10-20 μs with a frequency of 250 KHz providing a 25%-50% duty cycle, so that the resulting laser beam will have enough power to penetrate a users skin but the total energy output rate per area is low enough to maintain eye safety if accidentally shined into a persons eyes. In many devices the laser diode 210 is initially provided with a specific power output that deteriorates over time until the laser diode 210 must be replaced (e.g. after 3000-5000 hours of use).
FIG. 5 is a flow diagram 500 of a method of controlling the duty cycle of a laser diode, according to an exemplary embodiment of the invention.
In an exemplary embodiment of the invention, laser diode 210 is controlled by a controller 240 that detects ( 510 ) the power output of the laser diode. Optionally, controller 240 compares the power output to a stored value to determine if the power output is within a tolerance range ( 530 ) or if laser diode 210 has become weaker and is underperforming.
If the power output is within the tolerance range then the controller continues to periodically monitor the power output of laser diode 210 . Otherwise controller 240 calculates ( 540 ) an amended duty cycle that will provide the desired power output, for example by increasing the pulse length or by raising the activation frequency of laser diode 210 . Controller 240 changes ( 550 ) the duty cycle, so that device 100 maintains a constant power output. Optionally, controlling the duty cycle enables prolonging the lifetime of using device 100 without replacing laser diode 210 , although the intensity of laser diode 210 deteriorates over time. Optionally, the duty cycle may vary from less than 50% to more than 70%, for example from 10% to 100% to maintain a constant power output.
In an exemplary embodiment of the invention, a stronger laser diode (e.g. 100-900 mw) is used while providing the same power output as generated by a weaker laser diode (e.g. less than 100 mw) that is continuously on (100% duty cycle). As a result the laser beam is safer even though it is more intense since the beam is on intermittently and the target can cool off between pulses. When applying the beam to a user's skin the same overall power is delivered over the same amount of time.
Based on the above description it should be noted that device 100 includes a number of features that enhance user safety and/or enhance clinical efficiency:
1. A visible indication surrounding the laser beam to provide indication of the position of the laser beam;
2. A stronger laser beam with a controlled pulse length and duty cycle to prevent eye damage, since the beam is active only for a short period of time in every second;
3. A laser beam that is dispersed over a wide area to enable treating larger areas simultaneously with an eye safety light beam;
4. A secure activation switch that is only activated when pressing it against the target area.
It should be appreciated that the above described methods and apparatus may be varied in many ways, including omitting or adding steps, changing the order of steps and the type of devices used. It should be appreciated that different features may be combined in different ways. In particular, not all the features shown above in a particular embodiment are necessary in every embodiment of the invention. Further combinations of the above features are also considered to be within the scope of some embodiments of the invention.
It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove. Rather the scope of the present invention is defined only by the claims, which follow. | A laser therapy device, including: a laser diode that is adapted to produce a monochromatic laser beam; a lens that is adapted to receive the beam directly from the laser diode and exploit the natural divergence of the laser diode to form an essentially coherent monochromatic, collimated beam; wherein the formed beam is adapted to form on a plane perpendicular to the direction of propagation of the beam an elongated illuminated area in which the length of the illuminated area is at least twice the size of the width of the illuminated area; a controller that is adapted to control activation of the laser diode; an encasement enclosing the laser diode, the lens and the controller; wherein the encasement is adapted to be hand held by the user. | 1 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.