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BACKGROUND OF THE INVENTION
This invention relates generally to debarking of logs for pulp manufacture and more particularly to an apparatus and method for providing steam to the outside surface of the logs during their passage through the debarking drum, thereby heating the bark and improving debarking performance.
During winter, it is common for pulp logs which are stored outdoors prior to debarking to be in a frozen condition. This makes debarking difficult, and since it increases the time necessary for debarking to be accomplished, it also reduces the debarking throughput capacity of the mill.
Steaming frozen pulp logs is known to ease the removal of bark. A number of different steaming methods have been used. One steaming method for continuous drum debarking is to feed the frozen pulp logs through a stationary array of steam nozzles immediately prior to their entry into the debarking drum. This method has the disadvantage of being unable to preheat all surfaces of the feed logs during the debarking process. This is so because the logs in the feed chute are steamed as they pass the steam nozzles while sliding toward or into the debarking drum with little or no tumbling motion. The limited exposure of the log surface to the steam results in non-uniform thawing and a temporary surface warming which, in many instances, results in glazing, or icing, of the bark surface and, consequently, non-uniform debarking effectiveness.
Another method of steaming logs for debarking is to introduce the steam into the debarking drum in a substantially radial direction. This is accomplished by means of a compartmented annular steam distribution ring, in conjunction with a circumferential sliding valve which provides steam pressure through sequential steam ports in the drum wall. Commonly, the steam from the distribution ring compartments is distributed bidirectionally via hollow longitudinal ducts and thence into the drum through radial openings.
All steaming or thawing techniques presently employed provide some degree of success, but all also are subject to varying degrees of inadequacy. Out of roundness of the annular steam distribution ring can cause loss of steam pressure at entry into the drum interior and also leakage between the sliding valve and the ring as can wear of the mating surfaces of these two members. Steaming or water spraying in the log feed chute produces massive quantities of polluted water and may permit re-icing of some logs before they enter the debarking drum.
Also, because of its orientation, the circumferential sliding valve provides an opportunity for entrapment of foreign material between the valve surface and the annular steam distribution ring. This compromises the seal integrity at the contact interface between these two members. In addition, wear of the circumferential sliding valve will prevent closure of the clearance gap between the ring and valve necessary to minimize steam leakage and loss of steam pressure. Drain back of condensate from the ducts within the drum will find its way into the steam distribution ring and from there into the steam valve. This necessitates a drain off provision which, in a steam pressurized valve, may make it difficult to maintain desired steam pressure. Finally, introduction of the steam through the steam distribution ring at an intermediate location along the length of the debarking drum makes it difficult to ensure desired distribution of steam in both longitudinal directions within the debarking drum. This is a consequence of the steam having to travel in two opposite directions through the ducts from the steam distribution ring.
The foregoing illustrates limitations known to exist in present devices and methods. Thus, it is apparent that it would be advantageous to provide an alternative directed to overcoming one or more of the limitations set forth above. Accordingly, a suitable alternative is provided including features more fully disclosed hereinafter.
SUMMARY OF THE INVENTION
In one aspect of the present invention, this is accomplished by providing a steam distributing valve for sequentially introducing steam axially into the ends of hollow longitudinal log-tumbling staves which are attached to the interior wall of a rotating debarking drum. The steam is introduced at the log feeding end of the drum including a manifold arranged for sequentially providing pressurized steam communication with an open end of one or more of the staves, each stave having one or more apertures along its length for communication with the inside of the embarking drum; and pressurized steam feeding means for pressurizing the manifold.
The foregoing and other aspects will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawing figures.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a fragmentary end view of the log feed end of a debarking drum fitted with the present invention;
FIG. 2 is a partially sectioned side elevation view of the valve of the present invention; and
FIG. 3 is a fragmentary perspective view of a single stave.
DETAILED DESCRIPTION
FIG. 1 is a fragmentary elevation end view of a debarking drum 100 incorporating the present invention. Inlet ring 61 defines the drum inlet opening diameter, and is fixed to drumhead 60. Drumhead 60 projects inwardly from drum shell 40 and is fixed to the ends of log-tumbling staves 50 to cover their ends and provide a flat annular surface at the end of drum 100. Steam passages 51 are provided in head 60 and are aligned and connected, one with each stave at its end adjacent to the debarking drum inlet to communicate with the hollow interior of the longitudinal staves. A wear ring 12 shown as a preferred embodiment is fixed to head 60 and is provided with steam passages 26 to communicate through steam passages 51 of head 60, with the hollow interior of staves 50 through stave openings 53 at the inlet end of drum 100.
Valve 150, mounted on the ground or other permanent supporting structure, is placed axially upstream of drumhead 60 in a position to cooperate with stave inlet openings 53 through head passages 51 and, if used, steam passage 26 of wear ring 12 in its preferred embodiment. Valve 150 is preferably provided with two support legs 108 and cross braces 109 to assure structural rigidity. Joint connectors 105 are mounted on base 200 and are connected to support legs 108 by pivot pins 104 to permit articulation of support legs 108 with respect to base 200. At the top of legs 108 are flexible joints 110 upon which is mounted steam manifold 80.
Manifold 80 consists of header 34 which is a curved hollow member which is pressurized by steam through steam inlet 30 and which has at least on outlet port through which steam is fed through apertures 26 of wear ring 12 to stave openings 53. Header 34 is maintained in contact with wear ring 12 by the biasing action of cylinders 115 acting upon support legs 108. At the leading edge of manifold 80, with respect to the travel of wear ring 12 past header 34, is shown an angled plowing wear ring doctor 32 which is a scraper provided to remove foreign material from the flat surface of wear ring 12 so that it will not interfere with sealing between header 34 and wear ring 12. Wood, bark, dirt and other foreign materials being fed into the drum inlet is prevented from falling onto the valve by a shield ring 36, projecting axially upstream from drumhead 60. If trapped within the interface between header 34 and wear ring 12, such detritus could interfere with sealing.
FIG. 2 is a side elevation view of valve 150 presented to further illustrate features of the valve. Inlet ring 61 is surrounded by and secured to head 60 which in turn projects inwardly from drum shell 40. Head 60 is permanently secured to shell 40 and provides passages through which steam may travel to the ends of staves 50. Shield ring 36 is fixed to and projects axially outwardly from the log feeding side of head 60 such that shield 36 protects valve 150 from falling debris.
Wear ring 12 overlays and is fixed to head 60 to provide a smooth flat face against which face seal 20, which is fixed to seal base 21, can provide a positive seal against steam pressure. Seal base 21 is fixed to header 34 surrounding steam outlet port 37 of header 34 to provide steam communication through apertures 26 of wear ring 12 and 51 of drumhead 60 to stave opening 53 of stave 50. Header 34 is pressurized through steam inlet 30 from a flexible steam connection (not shown). Flexible joints 110 at the top of support legs 108 provide articulable support to manifold 80. Legs 108 are connected by pivot pins 104 to flex joints 105 mounted on base 200 so that valve 150 has the two degrees of articulation freedom required to maintain face seal 20 parallel to wear ring 12 during axial displacements of drum shell 40. Contact between face seal 20 and wear ring 12 is maintained by means of the bias provided by cylinders 115. These cylinders are the preferred biasing apparatus but springs or other devices may be appropriate in some installations.
FIG. 3 presents a fragmentary partially sectional perspective view of a hollow longitudinal stave 50 secured to the drum shell 40. Save opening 53 provides entrance to a pipelike path along which steam can be axially fed in the debarking drum 100. Distributed along stave 50 are steam injection openings 70 which are preferably oriented substantially, tangentially throughout the length of the drum or at different regions along the length of the drum for releasing steam into the interior of debarking drum 100. The number and spacing of injection openings 70 depends upon the size of debarking drum 100 and its debarking capacity. Adjustment of steam thermal input according to the degree of defrosting and/or de-icing required is readily accomplished by means of a pressure control valve (not shown) attached to the supply line to steam inlet 30 for controlling steam pressure and flow. Changes in steaming capacity may also be accomplished by changing seal base 21 and face seal 20 on header 34 in order to vary the duration of time during which steam may flow into apertures 26 and 51 and, hence, vary and control the maximum steam throughput capacity for the valve system. | A steam distributing valve in contact with the log feed end of a rotatable debarking drum is supported in such a manner that it is capable of moving slightly parallel to the drum axis in response to axial displacement of the drum. Full contact between the valve header and the drum end is maintained for sequentially providing pressurized steam to hollow longitudinal staves on the inner circumferential surface of the drum for thawing frozen logs for debarking. | 1 |
REFERENCE TO RELATED APPLICATION
[0001] This application is related to my co-pending application Ser. No. 09/412,581, filed Oct. 5, 1999, and Provisional Patent Application Ser. Nos. ______, filed November, 1999, and No. ______, filed January, 2000.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to containers which blend fluent materials stored in separate chambers when dispensing these materials. More particularly, the invention sets forth a container which cooperates with a removable vessel which communicates with the container for the purpose of introducing a separate fluid thereto. The container has a dispensing pump for discharging fluids stored within the container. The novel dispensing container finds application wherever fluid materials must be blended and dispensed in quantities appropriate for individual consumers. For example, the container may be utilized by consumers to store and dispense personal care products such as shampoo and hair conditioner, products such as oil and vinegar for preparing salad dressings, among others. Alternatively, the container may be utilized in industrial, commercial, institutional, medical, and scientific applications to blend active ingredients with carrier fluids, or to blend ingredients which would interact on contact with one another. The fields which may benefit from the invention are many and diverse.
[0004] 2. Description of the Prior Art
[0005] It is necessary from time to time to dispense several dissimilar fluent substances which must be separated from one another prior to being utilized, yet blended when utilized. In many cases, the precise proportions of the two substances cannot be determined until the last minute. If the two substances were separately stored, it would require extreme care to assure that they be accurately mixed together. Also, metering and dispensing of two separate substances is somewhat time consuming. Furthermore, separate metering and dispensing may expose one or both substances to contact with the air, airborne contaminants, light, or other detrimental influences.
[0006] Another aspect of containers is that in many cases, it is not feasible to provide separate fluids in proportional ratios. That is, it is frequently the case that one fluid is depleted while a usable quantity of another fluid yet remains. The fluid may be among the contents being dispensed, or alternatively may be a carrier fluid or a propellant. To this end, it would be desirable to provide a container which accommodates connection of a separate vessel containing one of the fluids.
[0007] This feature is shown in U.S. Pat. No. 5,908,107, issued to Baudin et al. on Jun. 1, 1999, wherein one vessel threads to another. However, the device of Baudin et al. lacks the mixing and dispensing pump of the present invention, and also lacks alignable ports or valves which enable immediate communication between the two receptacles when the detachable vessel is connected to the principal container.
[0008] It is convenient and effective to store, meter, blend, and dispense several substances from a single container in a manner assuring that plural contents be separated until the point in time at which they are used. The prior art has proposed containers which dispense plural contents. An example is seen in U.S. Pat. No. 3,850,346, issued to James E. Richardson et al. on Nov. 26, 1974. The subject dispenser of Richardson et al. is hand squeezed to dispense fluids, whereas the present invention includes a pump. Also, the present invention has an internal circuit cooperating with a removable vessel.
[0009] U.S. Pat. No. 5,439,137, issued to Jean-Francois Grollier et al. on Aug. 8, 1995, shows an aerosol type dispenser having plural fluid containers which dispense fluid. Unlike the present invention, there is no manual pump and no separable, connectable vessel.
[0010] U.S. Pat. No. 5,127,548, issued to Michel Brunet et al. on Jul. 7, 1992, features a dispenser having a plunger pump at one end and a discharge nozzle at the other end, in the manner of a hypodermic syringe. Actuation of the plunger ruptures a barrier which separates two stored fluids. The present invention lacks a frangible barrier which would require renewing for each subsequent use. Also, there is no mixing circuit incorporating check valves, as seen in the present invention, and no separable, connectable vessel. In the present invention, fluid is discharged through the pump, whereas this arrangement is not possible in the device of Brunet et al.
[0011] U.S. Pat. No. 5,588,550, issued to Robert C. Meyer on Dec. 31, 1996, illustrates a compartmented container which dispenses plural fluids in adjustable proportion. However, Meyer lacks a plunger pump and a dispensing circuit having check valves and an internal mixing chamber, as seen in the present invention, as well as a separable, connectable vessel.
[0012] U.S. Pat. No. 5,890,624, issued to William M. Klima et al. on Apr. 6, 1999, shows a dispensing container providing plural storage compartments and an indirectly operated plunger pump. Klima et al. has a dispensing circuit incorporating check valves and a mixing chamber. However, Klima et al. lacks a separable, connectable vessel, an agitator or mixing structure carried on the piston of the pump, and an internal support for supporting one of the storage compartments within the container. By contrast, these features are all seen in the present invention. Klima et al. has a plunger type pump. However, this pump is indirectly actuated by a trigger and associated linkage, whereas the pump of the present invention is directly actuated.
[0013] None of the above inventions and patents, taken either singly or in combination, is seen to describe the instant invention as claimed.
SUMMARY OF THE INVENTION
[0014] The present invention affords a hand held, pump action dispensing container or dispenser which is suitable for enabling consumers to blend and dispense many different fluids. The novel container has a storage receptacle in the form of a jar or bottle open at one end, and threads for securing a cap which bears a discharge nozzle. Optionally, the storage receptacle is divided into several compartments each intended to contain one fluid. The compartments are, in different embodiments, arranged side by side, one above the other, or one within another. Fluids contained within the compartments may be mixed in any desired proportion prior to discharge. The fluids are mixed or blended internally within the container prior to discharge.
[0015] The novel container has an associated separate auxiliary vessel which is connectable thereto. The separate vessel contains a second fluid which may interact with the first fluid contained within the container, or which may be a carrier fluid, a propellant, such as pressurized gas, or which may serve some other purpose. The container has passages which are opened by installing the separate vessel in the container. These passages establish communication between a compartment of the dispenser and the separate vessel. Communication occurs only when the separate vessel is installed in the container of the dispenser. Selectively opened passages enable residual pressure, in containers operated by pressurized propellant, to be vented relieved prior to opening the container, and without unduly depleting the source of propellant. Withdrawal of the vessel closes passages such that no undesired leakage to the outside of the container occurs.
[0016] A principal application of the invention is to provide pressurized propellant gas in a small, inexpensive vessel so that the principal container can be economically fabricated from an inexpensive material such as plastic. The pressure vessel can be fabricated from aluminum, steel, or any other suitable material.
[0017] The pressure vessel is removable from the principal container. This leads to certain advantages apart from cost of the container and attachable vessel. For example, depletion of one of the fluids need not cause the container and any remaining quantity of the other fluid to be discarded. Both fluids can be renewed as desired. Therefore, mismatches in quantity between propellant and the fluid being dispensed can be overcome. Both the fluid being dispensed and the propellant can independently, and at any time, be renewed as required. This feature enables usage of the container to continue with minimal regard for depletion of either propellant or of the fluid being dispensed.
[0018] A dispensing circuit enclosed within the container has a pick up tube for each compartment of the container, a common mixing chamber, and check valves to prevent cross contamination of storage compartments by backflow within the mixing circuit and to isolate the mixing chamber from exposure to the outside atmosphere.
[0019] The dispensing circuit and its conduits are secured to the cap. One of several types of pumps are incorporated to achieve forced dispensing. A manual plunger type pump is one possible type of pump. The plunger pump operates by direct action, that is, its upper portion is contacted by the user's hand and depressed. Depressing the plunger directly pressurizes fluid contained in the mixing chamber. Pressurized fluid can escape only through the discharge nozzle. A spring returns the plunger to its original position where it is ready for the next pressurizing stroke. The return stroke generates a partial vacuum in the mixing chamber which recharges the mixing chamber with fluids retrieved from storage. An optional proportioning valve adjusts proportions of fluids retrieved from storage. An electrically operated pump is an alternative to a manual pump.
[0020] Optionally, paddles or vanes are carried on the pump to improve blending within the mixing chamber. This option is used when highly viscous fluids are to be mixed, or when dispensing any fluids which resist spontaneous mixing. In a further option, a support cage or frame for supporting a small storage container within the bottle or jar depends from the cap.
[0021] A significant advantage of the invention is that preexisting spray heads can be utilized. This is of interest to manufacturers who will be able to utilize existing tooling to fabricate the spray head.
[0022] Another advantage of the invention is that the container, together with its internal circuits and valve features, can be manufactured by known molding techniques in a homogeneous single part, or in relatively few mutually attachable parts. Materials utilized to fabricate the container are readily recyclable.
[0023] Accordingly, it is an object of the invention to provide a hand held dispenser which blends and dispenses plural fluids which must be stored separated from one another.
[0024] Another object of the invention is to provide a hand held fluid dispenser which has a removably attachable auxiliary vessel, and which dispenser receives fluid from the auxiliary vessel.
[0025] It is another object of the invention that the dispenser and auxiliary vessel establish paths of communication therebetween to enable the various fluids to contact one another, and to close these paths of communication to prevent undesired discharge of the contents of the dispenser.
[0026] It is a further object of the invention to provide a mixing chamber for mixing fluids, which mixing chamber is isolated from the outside atmosphere.
[0027] Yet another object of the invention is to provide apparatus enabling standard pump spray dispensers to be readily converted from single fluid operation to blending and dispensing operation.
[0028] Still another object of the invention is to vary proportions of fluids being mixed and dispensed.
[0029] An additional object of the invention is that the dispenser be manufactured by molding techniques, and that discarded dispensers be readily recyclable.
[0030] Still another object of the invention is to enable pressurized dispensing containers formerly fabricated from steel to be fabricated from inexpensive materials, with only the vessel containing pressurized propellant to be fabricated from metals and their alloys.
[0031] It is a further object of the invention to vent residual pressure in propellant operated dispensing containers when dispensing is finished, without depleting the source of pressurized propellant.
[0032] Yet another object of the invention is to provide direct; actuation of the pressurizing plunger, and to discharge pressurized fluids through the cap.
[0033] It is an object of the invention to provide improved elements and arrangements thereof in an apparatus for the purposes described which is inexpensive, dependable and fully effective in accomplishing its intended purposes.
[0034] These and other objects of the present invention will become readily apparent upon further review of the following specification and drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0035] Various other objects, features, and attendant advantages of the present invention will become more fully appreciated as the same becomes better understood when considered in conjunction with the accompanying drawings, in which like reference characters designate the same or similar parts throughout the several views, and wherein:
[0036] [0036]FIG. 1 is a partially exploded, cross sectional, side elevational view of a dispensing container which may incorporate the present invention.
[0037] [0037]FIG. 2 is a cross sectional, side elevational view of a second embodiment of a dispensing container which may incorporate the present invention.
[0038] [0038]FIG. 3 is a top plan detail view of the upper center of FIG. 1.
[0039] [0039]FIG. 4 is a top plant detail view of the upper center of FIG. 1, showing an adjustment from the positions shown in FIG. 3, made by mutually rotating the components relative to one another.
[0040] [0040]FIG. 5 is a top plan view of a dispensing container which may incorporate the present invention.
[0041] [0041]FIG. 6 is a side elevational, cross sectional view of an alternative embodiment of a dispensing container which may incorporate the present invention.
[0042] [0042]FIG. 7A is a side elevational, cross sectional view of an embodiment of the invention incorporating a removable auxiliary fluid containing vessel.
[0043] [0043]FIG. 7B is a diagrammatic, side elevational detail view of an embodiment of the invention, showing closure of fluid circuits when an auxiliary fluid vessel is removed from the host container.
[0044] [0044]FIG. 7C corresponds to FIG. 7B, but shows the auxiliary fluid vessel installed in the host container.
[0045] [0045]FIG. 8 is a side elevational, cross sectional view of a second embodiment of the invention, incorporating a removable auxiliary fluid containing vessel.
[0046] [0046]FIG. 9 is a side elevational, cross sectional view of an embodiment of the invention incorporating an electrically operated pump.
[0047] [0047]FIG. 10A is an enlarged, side elevational detail view, shown mostly in cross section, of an auxiliary fluid vessel.
[0048] [0048]FIG. 10B is similar to FIG. 9A, but shows an internal sliding valve projecting from the auxiliary vessel.
[0049] [0049]FIG. 11 is a perspective detail view, partially broken away to reveal internal detail, of an auxiliary vessel similar to that of FIG. 11A, but modified to discharge fluid from a bottom surface.
[0050] [0050]FIG. 12 is a side elevational, cross sectional view of an embodiment of the invention showing a plurality of auxiliary vessels associated with one dispensing container.
[0051] [0051]FIG. 13 is a side elevational view of another embodiment of the invention depicting plural auxiliary vessels.
[0052] [0052]FIG. 14 is a side elevational view of a component which attaches additional auxiliary vessels to those of FIG. 13.
[0053] [0053]FIG. 15 is a side elevational view, shown mostly in cross section, of an embodiment featuring an interlock which discharges pressurized propellant into the novel container only during dispensing of the contents of the container.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0054] The present invention improves upon the container shown in my co-pending application Ser. No. 09/412,581, filed Oct. 5, 1999, which is incorporated therein by reference. Reviewing the subject matter of the co-pending application, and as shown in FIG. 1 of the drawings, novel dispensing container 10 is seen to comprise a storage bottle 12 having a floor 14 , a lateral wall 16 , and an open upper end 18 . A receptacle 20 for storing a fluid for subsequent dispensing is defined within bottle 12 . Container 10 stores two fluids separately, and can blend these fluids immediately prior to dispensing. A second receptacle 22 is defined within storage vessel 24 . Storage vessel 24 is dimensioned and configured to be insertable into, contained within, and readily retrieved from receptacle 20 .
[0055] A cap 26 closingly engages upper end 18 of storage bottle 12 . Components of a mixing and dispensing circuit and a pump for pressurizing fluids being dispensed are carried on cap 26 . The mixing and dispensing circuit includes a first pick up tube 28 extending from cap 26 into receptacle 20 , terminating near floor 14 . A second pick up tube 30 depends from cap 26 , extending to near the bottom of receptacle 22 of storage vessel 24 . Pick up tubes 28 , 30 discharge their respective retrieved fluids into a mixing chamber 32 .
[0056] Mixing chamber 32 is defined within a generally cylindrical member 34 . A pump is provided by a plunger 36 which is slidably disposed within cylindrical member 34 and accessible to manual contact from above cap 26 . The pump pressurizes and propels fluids contained within mixing chamber 32 . Plunger 36 includes a head 38 formed to define structure which cooperates with a user's thumb or finger, and a discharge nozzle 40 opening to the outside atmosphere. Circumferential ribs 41 project outwardly from plunger 36 at that portion contacting the interior surface of member 34 , for improving engagement of an external object. Illustratively, it is easy to grasp plunger 36 manually when assembling container 10 when ribs 41 engage the fingertips. The function of member 34 will be described hereinafter.
[0057] The dispensing circuit includes a first conduit 42 formed in pick up tube 28 , a second conduit 44 formed in pick up tube 30 , mixing chamber 32 , and a discharge conduit 46 formed in head 38 of plunger 36 . Discharge conduit 46 is disposed to conduct pressurized fluid from the pump to discharge nozzle 46 . Conduits 42 , 44 , and 46 are disposed in fluid communication with chamber 32 , subject to respective check valves 48 , 50 , 52 . Check valves 48 , 50 prevent back flow of blended fluids from chamber 32 into their respective receptacles 20 , 22 , to preclude cross contamination of stored fluids. Check valve 52 closes chamber 32 to fluid communication with the outside atmosphere, thereby minimizing possible deterioration of mixed fluids due to contact with air and airborne contaminants.
[0058] When plunger 36 is depressed by the user from the ready position shown in FIG. 1, plunger 36 imposes pressure on fluids contained within chamber 32 . These fluids can escape only through conduit 46 , and are subsequently discharged through nozzle 46 . A return spring 54 urges plunger 36 upwardly towards the ready position, thereby generating a partial vacuum within chamber 32 . This vacuum draws fluids from receptacles 20 , 22 past check valves 48 , 50 into chamber 32 .
[0059] Plunger 36 performs the further function of actively mixing or blending fluids drawn into chamber 32 . Mixing vanes or blades 56 project downwardly from plunger 36 such that they have a tendency to stir and mix fluids in chamber 32 .
[0060] A support cage or frame 58 is attached to that portion 60 of cap 26 projecting into receptacle 20 of bottle 12 . Support frame 58 surrounds vessel 24 and retains vessel 24 against portion 60 of cap 26 .
[0061] In the embodiment of FIG. 1, vessel 24 is contained within receptacle 20 of bottle 12 , and is removed therefrom by withdrawing cap 26 . Cap 26 has threads 62 which engagingly mate with threads 64 formed in bottle 12 . Pick up tube 28 passes through an upper opening 66 and a lower opening 68 formed in vessel 24 so that pick up tube 28 has access to fluid stored below vessel 24 in receptacle 20 . Vessel 24 and pick up tubes 28 , 30 are withdrawn from bottle 12 when cap 26 is unthreaded and removed.
[0062] Referring now to FIG. 2, in another embodiment of the invention, container 110 has two fluid storage receptacles 120 , 122 formed in bottle 112 . Receptacles 120 , 122 are separated from one another by an interior partition wall 102 . Bottle 112 is closed by cap 126 . Pitch of threads 162 , 164 is modified from the embodiment of FIG. 1 so that cap 126 is fully installed prior to interference occurring between pick up tubes 128 , 130 with wall 102 . Wall 102 and the bottom portion 160 of plunger 136 are dimensioned and configured so that lower portion 160 of plunger 136 contacts wall 102 , thereby sealing and separating receptacles 120 , 122 .
[0063] Cap 126 carries a member 134 and a plunger 136 , which are both essentially similar to member 34 and plunger 36 of FIG. 1. The only difference between the embodiments of FIG. 1 and FIG. 2 is that receptacles 120 , 122 in FIG. 2 are both formed integrally with bottle 112 . Optional mixing blades 41 are omitted from the embodiment of FIG. 2. The embodiment of FIG. 2 is appropriate where the proportions of the two fluids approach equality in the blended mix.
[0064] Both embodiments incorporate an adjustable proportioning valve disposed to selectively vary proportions of fluids entering the mixing chamber. This feature will be described in terms of the embodiment of FIG. 1, although it will be understood that the operative principles are equally applicable to the embodiment of FIG. 2. Turning now to FIG. 3, floor 70 of member 34 is seen to have an arcuate opening 72 which exposes upper opening 74 of conduit 42 (see FIG. 1) and upper opening 76 of conduit 44 (see FIG. 1) to fluid communication with chamber 32 . Member 34 may be grasped by a knurled, ridged, or otherwise textured collar or flange 78 (see also FIG. 1) and rotated to vary the cross sectional exposed area of openings 74 , 76 . Member 34 is rotatably contained within section 60 of plunger 26 so that this adjustment is possible.
[0065] [0065]FIG. 4 shows adjustment which has been made from the relative positions of member 34 and the bottom of portion 60 of cap 26 originally shown in FIG. 3. In FIG. 3, opening 74 is fully uncovered, and opening 76 is partially obstructed by floor 70 of member 34 . In FIG. 4, member 34 has been rotated in the direction of arrow 80 with the result that opening 74 is now partially obstructed and opening 76 is fully open. The proportions of respective fluids which will be drawn into chamber 32 by suction on the return stroke of plunger 36 will vary accordingly. Proportions of fluids entering chamber 32 are therefore infinitely adjustable within the range enabled by the cross sectional area of conduits 42 , 44 and opening 72 .
[0066] [0066]FIG. 5 shows the externally visible components of container 10 , as they relate to adjustment of proportion of the fluid mix. A pointer 82 formed in flange 78 is arranged to align with index marks of an index scale 84 molded into or printed on cap 26 . Rotation of member 34 in directions indicated by arrow 86 by grasping flange 78 will be reflected by different relative positions of pointer 82 and scale 84 .
[0067] [0067]FIG. 6 shows an embodiment particularly adapted for modification of pre-existing spray dispensers not originally designed to incorporate blending features. Container 210 includes a storage bottle 212 having a floor 214 , a lateral wall 216 , and an upper edge 218 . A receptacle 220 for storing a fluid for subsequent dispensing is defined within bottle 212 . A second receptacle 222 is defined within storage vessel 224 . Storage vessel 224 is dimensioned and configured to be insertable into, contained within, and readily retrieved from receptacle 220 .
[0068] The embodiment of FIG. 6 departs from that of FIG. 1 in that vessel 224 is configured to be supported from upper edge 218 . To this end, vessel 224 has a flange 225 which will come to rest on upper edge 218 when vessel 224 is inserted into receptacle 220 of bottle 212 . Cap 226 has a horizontal member 227 which entraps flange 225 when cap 226 is threaded to bottle 212 .
[0069] The spray pump of the embodiment of FIG. 6 operates similarly to that of FIG. 1, but is adapted to be compatible with vessel 224 . A mixing chamber 232 is formed within a housing 234 formed at the top of vessel 224 . A first pick up tube 228 depends from member 234 and passes through vessel 224 . A telescopic tubular extension 235 extends nearly to the floor 214 of bottle 212 . Fluid drawn by suction from the pump will enter extension 235 , pass through pick up tube 228 , and pass by check valve 248 to enter mixing chamber 232 . A second pick up tube 230 depends from member 234 and extends nearly to the bottom of vessel 224 . Fluid drawn by suction from vessel 224 is conducted through tube 230 past check valve 250 to enter mixing chamber 232 .
[0070] The pump of container 210 includes a plunger 236 slidably disposed on cap 226 and a head 238 which is the equivalent of that of the embodiment of FIG. 1. A housing 233 acts in concert with cap 236 to form a suction chamber 237 which is in fluid communication with mixing chamber 232 . A check valve 252 carried in housing 233 separates mixing chamber 232 from suction chamber 237 . Preferably, check valves 248 , 250 , and 252 each have a spring urging the respective valve into the closed position. These springs are sufficiently weak so that their associated valves will open responsive to suction established when plunger 236 moves upwardly responsive to return spring 254 after the user has removed manual pressure from plunger 236 . Container 210 has a dispensing circuit including the conduit provided by pick up tubes 228 , 230 , mixing chamber 232 , suction chamber 233 , and a discharge conduit 246 formed in head 238 . The overall function of the dispensing circuit of container 210 is similar to that of container 10 as regards pumping action, check valve operation, retrieval of fluids from receptacles 220 , 222 , and dispensing of blended fluids under pressure from the pump. The pump utilizes plunger 236 in a manner similar to that of plunger 36 of container 10 . In container 210 , blending may occur in chamber 237 as well as in chamber 232 . The significant advantage of container 210 is that insertion of vessel 224 into bottle 212 readily converts a standard pump dispensing container (not shown) into a blending dispensing container. Most of head 238 and plunger 236 can be adapted for use in container 210 , this requiring-a limited degree of truncation of the original suction chamber and downwardly depending portion thereof from the original head and plunger (not shown).
[0071] Progressive depletion of fluids stored in the various receptacles of all embodiments may be accommodated in any suitable way. Air relief valves (not shown) may be incorporated where desired. A source of compressed gas may be provided to prevent collapse or inoperability upon depletion of stored fluids. Alternatively, one or more receptacles may be flexible, so that they collapse in controlled fashion as their contents are removed.
[0072] [0072]FIG. 7 shows a modification of the embodiment of the embodiment of FIG. 2. The embodiment of FIG. 7 shares many structural features with that of FIG. 2, and reference numerals common to both Figures indicate structurally identical features. These features are described prior, and therefore description need not be repeated with respect to FIG. 7. In the embodiment of FIG. 7, lateral wall 316 of container 310 has a recess 301 for receiving a separate auxiliary vessel 303 . An opening 302 admits fluids from vessel 303 into compartment 320 of container 310 . An externally operable valve 304 opens opening 305 formed in the floor of auxiliary vessel 303 . Fluids from compartment 320 are drawn into the mixing and dispensing circuit by the pump associated with plunger 136 . A laterally displaceable link 307 controls a valve 308 to open opening 302 when vessel 303 is inserted into recess 301 . A unidirectional check valve 309 is disposed within cap 326 to admit air into compartment 320 from the exterior thereof. This feature relieves vacuum which would otherwise be generated by operation of the pump. Other check valves (not shown) may be provided at other locations on dispensing container 310 to relieve vacuum which would otherwise interfere with operability.
[0073] [0073]FIGS. 7B and 7C illustrate how link 307 operates. Link 307 is disposed within lateral wall 316 of container 310 (see FIG. 7A). Link 307 has an opening 307 A and a section 307 B which projects to the left of wall 316 , into recess 301 . It will be seen by examining FIG. 7B that opening 302 is misaligned with opening 307 A. As a consequence, no communication is established between compartment 320 of container 310 and the exterior thereof.
[0074] After auxiliary vessel 303 is fully inserted or installed in container 310 , occupying recess 301 , it displaces link 307 by moving link 307 to the right, as depicted in FIG. 7C. This causes openings 302 , 305 , and 307 A to align, thereby establishing fluid communication between vessel 303 and compartment 320 . Although not shown, link 307 is preferably spring biased into the closed position of FIG. 7B.
[0075] [0075]FIG. 8 shows a modification of the embodiment of FIG. 7 wherein the opening of the auxiliary vessel is located at the top of the auxiliary vessel, rather than at the bottom thereof, as shown in the embodiment of FIG. 7. In the embodiment of FIG. 8, a check valve 550 is formed at the top of recess 501 . Auxiliary vessel 503 has a valve 504 biased by a spring 505 into the closed position. The upper surface of recess 501 is so configured that valve 504 is depressed when vessel 503 is inserted into recess 501 .
[0076] [0076]FIG. 9 shows an embodiment of the invention incorporating an electrically operated pump 700 which replaces the plunger operated pump of the previous embodiments. A battery 701 supplies power to pump 700 . A switch 702 disposed on the exterior of dispensing container 710 controls pump 700 .
[0077] [0077]FIG. 10A shows how a seal is provided for those embodiments utilizing the arrangement of valve 504 of FIG. 8. Auxiliary vessel 503 has a groove 520 which slidingly retains a tab 522 having an opening 524 and a flexible membrane 528 . Tab 522 projects beyond lateral side 526 of vessel 503 . When vessel 503 is inserted into its host container 510 (see FIG. 8), tab 522 is displaced to the left, as depicted in FIG. 10A. The displaced condition is shown in FIG. 10B. Valve 504 aligns with opening 524 and is urged by spring 530 to project upwardly therethrough. Upward travel of valve 504 is limited by stop 532 . Fluid contained within vessel 503 can now escape through valve 504 , which is a hollow tube, Valve 504 is aligned with the passageway associated with check valve 550 (see FIG. 8). The contents of vessel 503 thereby establish fluid communication with chamber 32 of the pump.
[0078] If desired, direction of discharge of the contents of the auxiliary vessel may be at the bottom thereof. This embodiment is shown in FIG. 11, wherein vessel 803 is generally equivalent to vessel 503 of FIG. 10A.
[0079] As described with reference to FIG. 12, plural attachable auxiliary vessels may be employed with one dispensing container. With only the portion 660 shown, the portion 660 corresponding to portion 60 of FIG. 1, it being understood that portion 60 is a part of a dispensing container (not shown in its entirety) generally similar to that of FIG. 1, three pick up tubes 628 , 629 , 631 project downwardly. Tube 628 communicates with receptacle 620 , which is either integrally formed with the associated dispenser container or alternatively as a detachable part thereof. Tubes 629 , 631 respectively communicate with separate auxiliary vessels 603 P, 603 B. Each vessel 603 A, 603 B removably connects to receptacle 620 , and communicates therewith by a respective pick up tube extension 641 , 643 . Fluids contained within vessels 603 A, 603 B, and receptacle 620 are drawn into the pump simultaneously when the pump operates.
[0080] Auxiliary vessels 603 A, 603 B are replenished by respective removably attachable auxiliary vessels 617 A, 617 B. Vessels 603 A and 617 A mutually attach by snap structures (not; shown) or in any other suitable way. Valves 651 A, 651 B control transfer of fluid into vessels 603 A, 603 B. Valves 651 A, 651 B may take the form of manual valve 304 (see FIG. 7A) or interference operated valve 308 (see FIG. 7A).
[0081] [0081]FIG. 13 shows a variation of the embodiment of FIG. 12, wherein receptacle 760 has external threads 765 for connection enabling mounting of auxiliary vessels 817 A, 817 B (see FIG. 14). Auxiliary vessels 703 A, 703 B are shown connected to receptacle 760 . Internal fluid communication among receptacle 760 and auxiliary vessels 703 A, 703 B is accomplished as discussed relative to other embodiments. Valves 751 A, 751 B are shown as part of associated vessels 703 A, 703 B, respectively. A unitary assembly uniting auxiliary vessels 817 A, 817 B is shown in FIG. 14, wherein a skirt 800 envelops vessels 817 A, 817 B. Skirt 800 has internal threads 865 which mate with threads 765 of receptacle 760 . Valve connectors 851 A, 851 B enable communication between each upper and lower pair of auxiliary vessels 703 A, 817 A or 703 B, 817 B.
[0082] [0082]FIG. 15 shows a mechanical interlocking feature optionally and preferably utilized with those embodiments of the invention wherein the auxiliary vessel contains a propellant gas under pressure. In the embodiment of FIG. 15, container 910 is generally structurally similar to any of the prior embodiments of the invention, but has an interlock feature which assures that pressurized propellant gas is released into container 910 from auxiliary vessel 903 only when the user is dispensing liquids contained within container 910 .
[0083] When head 938 is depressed, an arm 959 comes into contact with lever 961 of a tilt switch (not shown in its entirety) of auxiliary vessel 903 . The tilt switch may be generally conventional, being that type which opens when lever 961 is tilted from the horizontal orientation shown in FIG. 15. Propellant gas contained at pressures above ambient pressures within auxiliary vessel 903 enters chamber 920 , thereby propelling liquids (not shown) contained within chamber 920 into pick up tube 928 for ultimate ejection through head 938 in a manner similar to that of the other embodiments.
[0084] Releasing head 938 so that head 938 returns to the original position shown in FIG. 15 will release lever 961 to reassume its original position, thereby closing its associated tilt valve. This feature avoids unduly depleting auxiliary vessel 903 but more importantly spares container 910 from being subjected to injurious high pressures. Therefore, container 910 is fabricated inexpensively from materials such as plastics, whereas only auxiliary vessel 903 need be fabricated to standards appropriate for containing high pressures typical of gas propellants. Illustratively, auxiliary vessel 903 is fabricated selectively from metals and metal alloys, such as, for example, steel and aluminum.
[0085] The present invention is susceptible to variations and modifications which may be introduced thereto without departing from the inventive concept. For example, valves disposed upon the auxiliary vessel, and structure located on the dispensing container for opening the valves by interference may be reversed in their locations. Also, valves shown and described herein may be replaced by other types of valves. For example, valves actuated by insertion of auxiliary vessels into the host container could be tilt-lever valves (not shown), wherein a horizontal projection contacts a pivotal arm. When the arm is contacted, it pivots and opens the valve. Check valves may take the form of solid members or flaccid membranes which yieldably cover ports formed in solid walls of the container and its associated auxiliary vessels. In a further example, any of the novel improvements shown herein may be utilized with any of the embodiments of the dispensing containers described herein.
[0086] Additional features may be incorporated into any of the embodiments of the invention. For example, a pressure relieiE feature may be incorporated into those containers which operate by pressure. In a second example, a mechanical interlock, such as link 307 of FIGS. 7 A- 7 C, may be employed to vent pressure which would otherwise be unrelieved in various chambers and conduits of the novel container. This is accomplished by providing selectively overlapping contact of an auxiliary vessel with the link or other actuators of valves. The venting valve would be held open until after the fluid control valve closes. Thus pressure is vented after the source of pressure is closed.
[0087] It is to be understood that the present invention is not limited to the embodiments described above, but encompasses any and all embodiments within the scope of the following claims. | A dispensing container which stores two or more separated fluids and blends the fluids when dispensing. The container has two or more liquid receptacles and a cap which threads to the bottle. The receptacles include the open interior of the container, and an interior vessel separate and removable from the container. The cap is connected a mixing circuit which retrieves and blends fluids taken from the receptacles. A pump, which may be either manually or electrically operated, draws fluids from the receptacles and discharges these fluids after they are mixed. The dispensing container has at least one, and optionally a plurality of separate, attachable auxiliary vessels. The auxiliary vessels communicate with the mixing circuit or alternatively with one another. The auxiliary vessels are constructed to hold pressurized propellant, while the dispensing container is formed from plastic. Internal circuitry has check valves which relieve vacuum which would otherwise develop within the container, and includes valves which open responsive to auxiliary vessels being installed or inserted into the dispensing container. | 1 |
CROSS-REFERENCE TO RELATED APPLICATION
The present application is a continuation in part of applicant's application U.S. Ser. No. 09/465,543 filed Dec. 16, 1999 now U.S. Pat. No. 6,270,091. This application also claims the benefit of U.S. provisional application No. 60/112,744 filed Dec. 17, 1998 U.S. provisional application No. 60/306,259, filed Jul. 17, 2001.
BACKGROUND OF THE INVENTION
The field of the invention is sporting goods and the invention relates more particularly to snowboards, although boards made according to the teaching of the present invention can also be used on water or sand.
In the past, commercial snowboards have been limited in their ability to make sharp turns and maneuver over uneven surfaces and around moguls. In addition, they are awkward to store and transport.
U.S. Pat. No. 5,865,446 to Kobylenski, et al., attempted to address the limitations of the one-piece snowboard by creating an articulated two-piece snowboard that looks very much like a traditional snowboard cut in half and connected with flexible straps. Although the flexible connection appears to give the snowboard some additional maneuverability over a one-piece board by making one board into two shorter boards, the flexible connection results in some significant adverse maneuverability issues.
The bottom of the Kobylenski board is flat like a traditional, one-piece snowboard, so that each section still has problems moving over and around bumps and uneven surfaces. In addition, and most importantly, the snowboard still must be maneuvered using the edge of the board for turning and direction in a manner similar to the one-piece snowboard. This makes the snowboard less controllable using the stated design than one-piece snowboards for the following reason: by creating a flexible connection, the rider must now contend with two edges, one on each section. To maximize control, the full edge of each section needs to be in contact with the surface of the snow. In order for this to happen, the edges must remain in a straight line. This will require substantial effort on the part of the rider and the sections will normally not remain in a straight line.
The rider has two options when entering a turn, neither optimal. In the first, the forward foot will be angled into the turn while the trailing foot will tend to be pointed in the original direction. The weight will be on the front foot to make the turn, engaging the full edge of the front section, but with reduced effectiveness, since the edge of the back section is used only minimally—the turn is being performed primarily by the edge of the front section. If the rider inadvertently shifts his weight to the back section, that section will want to maintain the original direction and the board could easily become uncontrollable. In the second method of making the turn, the rider will have more equal weight on both sections, and the angle between the longitudinal axis of both sections will be less than 180 degrees on the side that is being turned toward. The problem with this approach is that only a fraction of the full edge of both sections will be engaged. This will result in decreased turning performance when compared to a one-piece snowboard.
The primary advantage becomes the primary disadvantage, since the flex in the middle prevents full engagement of both sections' edges. In summary, the use of Kobylenski's design of a two-piece snowboard with a flexible connector while retaining the same turning method that is used in the one-piece snowboard creates a board that is difficult to control in a turn.
The present invention introduces an entirely new design for snowboards, comprising two sections with a uniquely shaped convex bottom and joined with a connector. Quite different than the traditional flat-surfaced bottom, the bottom surface of the snowboard of the present invention is not only convex front to back, like the traditional snowboard, but in the preferred embodiment, also somewhat convex side to side. This allows it to move around and through rough, bumpy surfaces, including moguls. The convex bottom has one or more ridges which are used to maneuver and turn the board. The edge of the board is no longer the primary means of turning the board. The ridges are strategically placed on the bottom surface to accommodate various types of terrain and ride. Angled blades can be incorporated in the bottom surface for more aggressive turning capability. Shallow, blunt ridges are best used for fast downhill rides with fewer turns; deeper, sharper ridges are better suited for tighter turns and slower maneuvering. In the preferred embodiment, a springable connector provides enough flex for the rider to alternate turning first one direction, then the other, as the rider glides downhill, while the semi-rigid and non-twisting aspects of the connector provide the rigidity necessary to maintain control.
The sections can be disconnected for each transport and storage. A user can customize and modify the performance of the invention by: (a) interchanging sections with sections of differing physical and performance characteristics; (b) changing or moving ridges or blades on a section; and/or (c) changing to a different style of connector for joining the two sections.
BRIEF SUMMARY OF THE INVENTION
The present invention is an articulated, two-piece snowboard with separate front and rear sections joined together with a connector, each section providing a platform for one foot. In the preferred embodiment, the bottom surfaces of the sections are convex, with longitudinal ridges along the bottom; the sections are connected with a non-twisting, semi-rigid, springable connector. The sections may be detached from the connector for the purpose of transporting the snowboard or for the purpose of substituting a section or connector with different characteristics.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an exploded perspective view of the invention of the parent application of the present application.
FIG. 2 is a side view thereof.
FIG. 3 is a bottom view towards the bottom surface thereof.
FIG. 4 is a bottom view illustrating turning blades thereof.
FIG. 5 is a bottom view illustrating turning blades thereof.
FIG. 6 is a bottom view illustrating a tapered shape thereof.
FIG. 7 is a top view thereof.
FIG. 8 is a sectional view taken along line 8 — 8 of FIG. 7 .
FIG. 9 is a plan view thereof as it would appear in a turn.
FIG. 10 is a cross-sectional view taken along line 10 — 10 of FIG. 9 .
FIG. 11 is a plan view thereof.
FIG. 12 is a cross-sectional view taken along line 12 — 12 of FIG. 11 .
FIG. 13 is a plan view thereof.
FIG. 14 is a cross-sectional view taken along line 14 — 14 of FIG. 13 .
FIG. 15 is a cross-sectional view taken along line 15 — 15 of FIG. showing reinforced areas.
FIG. 16 is a perspective view of the connection assembly thereof, including the flexible sheath covering the spring.
FIG. 17 is a longitudinal cross-sectional view taken along line 17 — 17 of FIG. 16 .
FIG. 18 is a perspective view of the connection assembly thereof.
FIG. 19 is a cut-a-way perspective view of the connection assembly thereof.
FIG. 20 is an exploded perspective view of the connection assembly thereof.
FIG. 21 is a perspective view of an alternate embodiment of the connection assembly thereof, suing plates in place of the center cord.
FIG. 22 is a perspective view of the plates of FIG. 21 .
FIG. 23 is a fragmentary side view of the plates of FIG. 22 .
FIG. 24 is a side view of an alternate embodiment of the connection assembly thereof, using a ball and socket.
FIG. 25 is a rear side view of the front section of an alternative embodiment of the snowboard of FIG. 24 .
FIG. 26 is a side view of the connector of the snowboard of FIG. 24 .
FIG. 27 is a sectional view taken along line 27 — 27 of FIG. 26 .
FIG. 28 is a side view of an alternate embodiment of the snowboard of FIG. 26 .
FIG. 29 is a cross-sectional view taken along line 29 — 29 of FIG. 28 .
FIG. 30A is a top view of the present invention.
FIG. 30B us a cross-sectional view taken along line 30 B— 30 B of FIG. 30 A.
FIG. 31 is a side view of the snowboard of FIG. 30 A.
FIG. 32 is a bottom view illustrating the placement of ridges of the snowboard of FIG. 30 A.
FIG. 33 is a cross-sectional view of the present invention taken along line 33 — 33 of FIG. 30 A.
FIG. 34 is a perspective fragmentary view of attachment of connector to rear section.
FIG. 35A is a plan view of the present invention as it would appear in a turn.
FIG. 35B is a cross-sectional view taken along line 35 B— 35 B of FIG. 35 A.
FIG. 36A is a bottom view of an alternative embodiment illustrating placement of two ridges towards the outer edge of the bottom of each section.
FIG. 36B is a bottom view of an alternate embodiment illustrating placement of two ridges towards the outer edge and a single ridge in the center of the bottom of each section.
FIG. 36C is a bottom view of an alternate embodiment illustrating placement of six ridges on the bottom of each section.
FIG. 36D is a bottom view of an alternate embodiment illustrating placement of one ridge on the bottom of each section.
FIG. 37A is a cross-sectional view taken along line 37 A— 37 A of FIG. 36 A.
FIG. 37B is a cross-sectional view taken along line 37 B— 37 B of FIG. 36 B.
FIG. 37C is a cross-sectional view taken along line 37 C— 37 C of FIG. 36 C.
FIG. 37D is a cross-sectional view taken along line 37 D— 37 D of FIG. 36 D.
FIG. 38A is a plan view, partly in cross-section showing an alternate embodiment of a connector.
FIG. 38B is a longitudinal cross-sectional view taken along line 38 B— 38 B of FIG. 38C showing an alternate embodiment of a connector.
FIG. 38C is a top plan view of the alternative embodiment of the connection of FIG. 38 A.
FIG. 38D is an enlarged fragmentary view of the alternate embodiment of the connection of FIG. 38 A.
FIG. 38E is a fragmentary perspective view of the alternate embodiment of the connector of FIG. 38 D.
FIG. 38F is a perspective view of the alternate embodiment of the connector of FIG. 38 D.
FIG. 38G is a top view of the alternative embodiment of the connector of FIG. 38 D.
FIG. 39A is a side view of an alternative embodiment of a connector.
FIG. 39B is a side view of the alternative embodiment of the connector of FIG. 39A without the spring.
FIG. 39C is a cross-sectional side view of the alternate embodiment of the connector of FIG. 39 C.
FIG. 39D is a fragmentary perspective view of an arrangement of metal plates used in the alternate embodiment of the connector of FIG. 39 A.
FIG. 39E is an enlarged side view of the alternate embodiment of the connector of FIG. 39 F.
FIG. 39F is a side view of the alternate embodiment of connector which places the springable connection on the front and rear sections connected by an inflexible rod.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The preferred embodiment of the present invention, as best shown in FIG. 1, comprises a front section 54 and a rear section 56 joined with a springable connection assembly 55 . Although front section 54 and rear section 56 are depicted as identical, they may differ in size, shape or construction to alter the performance characteristics of the invention. The rider of the invention will place one foot on section 54 and one foot on section 56 , preferably with feet at angles to the longitudinal axis in a stance similar to that used by traditional snowboarders.
Connection of the Three Primary Parts of the Invention: Front Section, Rear Section and Springable Connection Assembly.
FIG. 1 illustrates how the three primary pieces of the invention, the front section, the rear section, and the springable connection assembly, are attached to one another. To connect the front section and the rear section to the springable connection assembly, block 60 R, preferably rectangular, is inserted into a slot, hollow or mating cavity 45 R and block 60 L is inserted into the slot, hollow or mating cavity 45 L. Block 60 L is primarily secured by two bolts 43 L which are inserted into two holes 64 L in the block and into threaded sleeves or holes in the wall of the mating cavity 45 L. In addition, a bolt 41 L is inserted through washer 67 L into sleeve or hole 53 L, where it passes through loop 80 L of the connection assembly and into a threaded receptacle and tightened. The purpose of bolt 41 L is to prevent separation of section 54 from the connection assembly in the event that bolts 43 L fail under stress. In the same manner, block 60 R is primarily secured by two bolts 43 R which are inserted into two holes 64 R in the block and into threaded sleeves or holes in the wall of the mating cavity 45 R. In addition, a bolt 41 R is inserted through washer 67 R into sleeve or hole 53 R, where it passes through loop 80 R of the connection assembly and into a threaded receptacle and tightened. The purpose of bolt 41 R is to prevent separation of section 54 from the connection assembly in the event that bolts 43 R fail under stress.
Front Section: Shape and Outer Surface.
The front section has a convex-shaped bottom the bottom surface of the section is not only convex parallel to the longitudinal axis as shown in FIG. 2, bit is also preferably convex perpendicular to the longitudinal axis, as shown in cross-sectional view in FIG. 8 . This would usually mean that the lowest part 66 of the bottom surface is lower than the outside edges 63 of the bottom surface. The outside edges 63 are usually rounded or curved upward to prevent the edges 63 from digging into the snow, except when usage may require less rounding and more of a sharp or pointed edge, such as steep terrain or stunt riding. The leading edge 57 in FIG. 2 is curved upward somewhat. The top surface 40 L of said front section is used as a platform for one of the rider's feet. Two rigid strips 49 , shown in FIG. 1, preferably metal, are connected to the top surface 40 L with screws or other connectors. Said strips provide longitudinal reinforcement for said section. The trailing edge 59 of the front section curves upward and then flattens as it forms the upper surface of a mating cavity 45 L; said mating cavity is a receptacle for block 60 L of the connection assembly 55 .
Front Section: Bottom Surface.
The bottom surface 42 L of the invention is best shown in FIG. 3 . Ridges 44 extend longitudinally along the bottom surface. The triangular shape of the ridges 44 are shown in cross-sectional view in FIG. 8 . (To better describe the shape of the ridges: if one were to extrude a triangle and place one of the flat surfaces of the three-sided extrusion against the bottom surface of the section, running lengthwise, one would then have a ridge.) The number of ridges can be varied in order to modify the performance characteristics of the invention.
In addition, the ridges themselves can vary. An alternate embodiment of a ridge is depicted in FIG. 8, where a blade 115 , made of metal or other hard material, protrudes from the bottom of one or more ridges to provide additional “bite” and improved control. Longitudinal blades facilitate movement in a direction parallel to the longitudinal axis of the section.
Blades may also be used to aid in turning and/or stopping, and are usually placed on the periphery of the sections. FIGS. 4, 5 , and 6 illustrate placement of blades and ridges. FIG. 4 shows two sets of turning blades 71 and 67 . Angled out blades 71 are pointed away from the longitudinal axis of the section to facilitate the turning of the front section in the direction of the turn. For example, the front section will turn right in a right-hand turn. Angled-in blades 67 on the rear section are pointed towards the longitudinal axis of the board so that the rear section will tend to turn in the direction away from the turn. For example, the rear section will tend to turn left in a right-hand turn, which places the invention in a curve to the right, and facilitates the turn. FIG. 4 also shows two sets of stopping blades. Angled-out stopping blades 69 have more stopping power than angled-in stopping blades 68 .
FIG. 5 shows one right turning blade on each section and one left turning blade on each section, rather than the two blades per side per section, as shown in FIG. 4 .
FIG. 6 depicts turning blades that are parallel to the sides of the sections, but since the sections are themselves slightly angled, this results in the blades 116 angled out and the blades 117 angled in, resulting in the functionality as the boards in FIGS. 4 and 5, with the additional advantage of the board shape working with the turning blades to further facilitate turns.
In all cases of ridges and blades, the convexness of the bottom surface perpendicular to the longitudinal axis combined with the ridges, including longitudinal, turning or stopping ridges, are some of the key differences between this invention and traditional snowboards or skis.
Front Section: Spacers.
FIGS. 1 and 7 show bumpers or spacers 47 L, located on the sides of the trailing edge of the front section. The spacers are preferably constructed of hard, resilient material such as a hard rubber or similar material.
Front Section: Internal Construction.
FIGS. 12, 14 , and 15 illustrate the internal construction of the invention. The inner core 50 is surrounded by a durable outer layer 51 . The inner core is preferably a carvable foam, but can be wood, composite or a similar material that helps to provide shape to the invention. The outer layer is preferably fiberglass resin and cloth, but can be any material that helps to provide a durable outer layer of adequate strength, such as an injection molded plastic, a composite, metal, carbon fiber, or any other similar material. Additional reinforcement for high stress areas may be desirable, depending on materials used. In the preferred embodiment, reinforcement material 52 is used in the trailing edge of the front section so as to reinforce the mating cavity which holds the connection assembly block. Reinforcement material is preferably a plastic that pours and molds into the desired shape, but can be any material that increases the strength and durability of the area, such as a high-strength plastic, composite, metal or any other similar material. A lengthwise band of the reinforcement material 48 is also used under strips 49 , as shown in FIGS. 14 and 15.
Rear Section: Same as Front Section.
FIG. 1 shows the rear section 56 to be a mirror image of the front section. Therefore, the description above of the front section applies also to the rear section, except that the leading edge 57 of the front section is the trailing edge 61 of the rear section, and the trailing edge 59 of the front section is the leading edge 58 of the rear section. And the part numbers use “R” instead of “L” as a suffix.
Connection Assembly: Overview.
FIG. 20 illustrates the connection assembly. The connection assembly resists movement from its unstressed position. In addition, it is advantageous if it can be easily disconnected from the front and back sections for storage and replacement purposes.
Connection Assembly: The Innermost Cord Within the Tube.
In FIG. 20, a cord 82 , preferably constructed of a strong, flexible material such as stranded cable, with loops 80 L and 80 R at each end, is inserted into a flexible tube 72 . The tube is preferably filled with a flexible filler material 86 , such as silicone. Flanges 70 L and 70 R are inserted into front end and back end of tube 72 , respectively.
Connection Assembly: Spring, Clamps and Block.
The tube 72 is inserted into a spring 78 . Circular clamps 74 and 76 are tightened around the front end of the spring. Circular clamps 79 and 81 are tightened around the rear end of the spring. Cord, tube, flexible filler, flanges, spring and circular clamps connect to form a spring assembly 65 . The blocks 60 L and 60 R are preferably a moldable, rigid material, such as plastic or resin.
Connection Assembly: Spring Assembly an Integral Part of Block.
The front end and rear end of the spring assembly are molded into block 60 L and 60 R, respectively. Making the spring assembly an integral part of the block anchors the spring assembly at each end and aims to prevent movement of the end of the spring in the direction of the coils, clockwise and counter-clockwise. The purpose of the circular clamps now becomes apparent—they provide asymmetrical projections within the block to help prevent the spring assembly from twisting and breaking loose inside the block. Tubes 62 L insert in holes 64 L to prevent damage to block 60 L from over-tightening of bolts 43 L (shown in FIG. 1 ). FIG. 18 illustrates the connection assembly. FIG. 19 is a cut-a-way of the connection assembly, showing the relationship of the spring assembly and block. FIG. 17 is a longitudinal cross-sectional view of the connection assembly.
Connection Assembly: Snow Barrier Covering on the Spring.
FIG. 16 illustrates a covering 84 over the spring, which may be made of rubber or other barrier to prevent show from lodging between the coils of the spring.
Connection Assembly: Non-twistable.
FIGS. 21, 22 , and 23 illustrate a non-twistable version of the connector. The cord 82 is replaced with a plate assembly, depicted in FIG. 22, comprised of preferably metal plates fastened with bolts. A bolt 88 passes through an upper plate 83 , a washer 90 , a middle plate 85 , a washer 90 , a lower plate 87 , and nut 89 , respectively. The plate assembly is positioned within the connector as shown in FIG. 21 . When attaching the connector to the front and back sections of the invention, the blocks 60 L and 60 R are inserted in the receptacles 45 L and 45 R, and the bolts 41 L and 41 R are inserted through a hole 73 of the connector and secured to the respective section.
Connection Assembly: Rigid Connector, Ball and Socket Joint.
FIGS. 24, 25 , 26 , and 27 illustrate a ball and socket joint that will provide motion in all directions with a rigid connector. The connector is a rod 94 , preferably metal, with spheres 93 L and 93 R at each end, as shown in FIG. 26. A horizontal slot 95 allows the rod 94 to swing left to right, horizontally. The spheres allow the sections to twist around their longitudinal axis. The spheres 93 L and 93 R are held securely within each section with a door 120 . Vertical motion could be added by including a vertical slot. Or full range motion could be implemented with a funnel-shaped hole, with the sphere at the narrow end and the rod having the.wide end of the funnel to move freely. FIGS. 28 and 29 illustrate a rigid connector for the ball and socket joint that would prevent twisting and would only allow movement in the horizontal plane. The spheres are flattened into discs 96 L and 96 R so that they will not move up and down, but only horizontally.
A preferred embodiment of the present invention, as best shown in FIG. 30A, comprises a front section 254 and a rear section 256 joined with a stiff but elastically bendable connector 255 . Although front section 254 and rear section 256 are depicted as identical, they may differ in size, shape or construction to alter the performance characteristics of the invention. The rider of the invention will place one foot on section 254 and one foot on section 256 , preferably with feet at angles to the longitudinal axis in a stance similar to that used by traditional snowboarders. A “stiff but elastically bendable” means a connector fabricated from a material such as spring steel. Other materials, such as polymeric materials of ultra high molecular weight polyethylene, polypropylene, and including composite polymers, can be used. The important quality is that of providing a stiff connection and yet, one that will bend with sufficient force. A typical connector stiffness is illustrated in FIG. 35A. A weight W of ten pounds is applied normal to the longitudinal axis of rear section 256 a distance D 1 of ten inches behind trailing edge 259 of front section 254 . This causes a bending of connector 255 . The amount of deflection D 2 measured 21.6 inches behind trailing edge 259 was 2.6 inches. This, of course, is just an example of a practical stiffness and it is possible to change this stiffness substantially and provide more deflection for a younger rider and less deflection for a heavier adult rider.
Connection of the Three Primary Parts of the Invention: Front Section, Rear Section and Connector.
FIG. 30 A and FIG. 34 illustrate how the three primary pieces of the invention, the front section, the rear section, and the connector is inserted into a channel, slot, or cavity 170 L in an open housing or block 150 L. Locking pins or bolts 151 L are inserted into holes 153 L and secured with nuts 152 L. Locking pins 151 L secure the connector to the front section. To connect the rear section to the connector, the connector is inserted into a channel, slot, or cavity 170 R in an open housing or block 150 R. Locking pins or bolts 151 R are inserted into holes 153 R. Locking pins or bolts 151 R secure the connector to the rear section.
Front Section: Shape and Outer Surface.
The front section has a somewhat convex bottom. The bottom surface of the section is not only convex parallel to the longitudinal axis as shown in FIG. 31, it is also preferably convex perpendicular to the longitudinal axis, as shown in cross-sectional view FIG. 30 B. This would usually mean that the lowest area, ridges 180 L of the bottom surface, are lower than the outside edges 182 L of the bottom surface. The leading edge 257 in FIG. 31 is curved upward somewhat. The trailing edge 259 of the front section also curves upward.
Front Section: Bottom Surface.
The bottom surface 242 L of the invention is best shown in FIG. 32 . Ridges or protrusions 180 L and 181 L extend somewhat longitudinally along the bottom surface. The centermost ridges 180 L are approximately parallel to the longitudinal axis. The outside ridges 181 L are slightly angled; when facing towards the front of the board, the forward end of the ridges on the left side of the front section are angled towards the left and the forward end of the ridges on the right side of the front section are angled towards the right. When the section is tipped onto its side by the rider, these ridges are engaged and cause the board to turn more tightly.
Front Section: Bottom Platform Width.
Longitudinal center ridges 180 L in FIG. 30B are the two lowest points on the bottom of the front section. They are, therefore, in contact with the snow, creating a platform on which the rider balances the section. The distance between the two center ridges 180 L is approximately 3 inches. A front section with a distance between the two center ridges 180 L of less than 3 inches will tip more easily from one side to the other, and will be less stable, making it more difficult to maintain a consistent side-to-side position. A front section with a distance between ridges 180 greater than 3 inches will be less likely to tip from side-to-side and will be more stable and easier to balance. The optimal platform width for a section will be determined by the size and shape of the section, as well as number and placement of ridges on the bottom of the section.
Front Section: Internal Construction
FIG. 33 illustrates the internal construction of the invention. The inner core 191 is surrounded by a durable outer layer 190 which has a right side 160 L. The inner core is preferably a carvable form, but can be wood, composite or a similar material that helps to provide shape to the invention. The outer layer is preferably fiberglass resin and cloth, but can be any material that helps to provide a durable outer layer of adequate strength, such as an injection molded or rotationally cast plastic, a composite, a metal, carbon fiber, or any other similar material. Additional reinforcement for high stress areas may be desirable, depending on materials used. In the preferred embodiment, reinforcement material 161 L is used in the trailing edge of the front section so as to reinforce the area around the embedded extension 162 L of the block 150 L. Reinforcement material is preferably a plastic that pours and molds into the desired shape, but can be any material that increases the strength and durability of the area, such as a high-strength plastic, composite, metal or any other similar material. If a section could be constructed with injection molded plastic or similar process, the carvable inner core and some other elements described herein may not be required.
FIG. 30 shows the rear section 256 to be a mirror image of the front section. Therefore, the description above of the front section applies also to the rear section, except that the leading edge 257 of the front section is the trailing edge 261 of the rear section, and the trailing edge 259 of the front section is the leading edge 258 of the rear section. And the part numbers use “R” instead of “L” as a suffix. The right side of the rear section is indicated by reference character 160 R.
Connector: Overview.
FIGS. 33 and 34 illustrate how the connector is attached to each section. The connector consists of one or more strips of a semi-rigid, flexible material, such as metal, ultra high molecular weight plastic, or other material with similar characteristics, or a combination of one or more such materials. The important characteristics of the connector are: that it flex from side-to-side in the horizontal plane; that it be unable to flex up and down in the vertical plane; that it not be able to twist so as to provide a stable riding platform; that it be sufficiently strong; that it resist movement from its unstressed position; and that it return to its unstressed position if moved into a different position. The attachment of the connector is such that it can be easily disconnected from the front and back sections for storage and replacement purposes.
Connection Assembly: Details.
The connector is preferably one strip of metal, or a side-by-side sandwich of two or more strips of metal. It may also include strips of other materials such as plastic or rubber in the sandwich. The resulting connector must be strong enough to resist flexing, but still be able to be flexed on demand by the movement of the rider's feet. FIG. 34 illustrates the attachment of the connector to the rear section. The front section will be the same, except for the numbering of the various items—the front section numbers end in “L” instead of “R”. Block 15 OR is open on two sides—the side facing the connector and the side facing the top. The end of connector 255 slides into channel 170 R. Holes 154 R in the connector line up with holes 153 R in the block. Locking pins or bolts 151 R are placed in holes 153 R and secured with nuts 152 R.
Operation of Preferred Embodiment; Turning the Invention.
A rider will place one foot on the front section of the invention and one foot on the rear section. The rider will preferably have both feet secured to the respective sections. Traveling downhill over the snow, the rider can pivot his feet to point to the left or to the right, causing the board to pivot in the same direction. When the rider pivots his front foot to point to the right, the front section will turn to the right, which causes the entire board to turn to the right. When the rider pivots his front foot to point to the left, the front section will turn to the left, which causes the entire board to turn to the left. This turning tendency can be increased by placing ridges on the periphery of the sections at an angle to the longitudinal axis of the section, enabling the rider to further change his direction of travel by tilting the front or rear section about its longitudinal axis by shifting his weight left or right. When the rider's weight is shifted left, for example, that section's left side will tilt down as depicted in FIG. 35 A and FIG. 35B, engaging ridges or blades that are angled to the left, and increasing the tendency of the section to turn left. Similarly, when the section is tilted down on the right, blades or ridges that are angled to the right will made contact with the surface, increasing the tendency of the section to turn right.
Stability.
The connector, when flexed, exerts a force against the flexion in an attempt to return to its unflexed state. This gives the invention a predictable stability. The sections will tend to stay in a straight line (an unflexed position), as illustrated in FIG. 30A, unless the rider proactively moves them out of the straight, unflexed position, as depicted, for example, in FIGS. 35A and 35B, as a turn to the left.
Ease of Connecting/Disconnecting Sections.
It is desirable to be able to easily connect and disconnect the sections. To this end, the connector is secured to each section with only two pins or bolts, easily removed by the rider. In an alternative embodiment for commercial production and use, the connector end can be dropped into a receptacle and secured with a hinged latch without the use of bolts to make it easier for the user to connect and disconnect.
Interchangeable Connectors.
The performance characteristics of the invention can be modified by using connectors with different flex characteristics. The lighter weight rider and the beginning rider might prefer a connector that is easier to flex, since the sections would be easier to maneuver. In addition, connectors can be varying lengths to accommodate the stride of different sized riders.
Interchangeable Sections.
Because invention performance can be modified by changing the characteristics of the front and rear sections, a rider may prefer one set of characteristics for the front section and another set of characteristics for the rear section. The rider can easily replace a front or rear section with a front or rear section having different characteristics. In fact, because the connection between front and rear sections may be identical and interchangeable, a rider can use a rear section from one sample of the invention as a front section, or a front section to replace a rear section in another sample of the invention.
Modifications to Section Bottom That May Change Performance.
Some of the characteristics of the invention that can be modified in order to change performance of the invention include: changing size, shape, contour, and number of ridges on the front and/or rear sections; changing the convexness of the bottom of the front or rear section; changing the length of a section; making ridges deeper or more shallow; modifying ridges with undulations on the ridges or ridges on the ridges. The sections may be identical mirror images as described in the preferred embodiment, or they may differ in shape and/or size.
Alternate Embodiments of Board Shape as Viewed from Above.
FIG. 32 illustrates the board shape as viewed from the bottom, approximating an oval shape, except that the inside curve is more pointed than the outside curve. Alternate embodiments of the board shape may have the outline shape of either the leading or trailing half of the section as different than depicted.
Alternate Embodiment of Lateral Cross Section.
FIG. 30B illustrates a cross-section of the preferred embodiment of the invention. An alternate embodiment of the board has a smaller or greater distance between the top surface and the bottom surface of a section.
FIGS. 37A, 37 B, 37 C, and 37 D illustrate alternate embodiments of various bottom shapes and ridge placements.
Alternate Embodiments of Bottom Surface.
Ridge Placement.
A single ridge 187 L may run longitudinally down the flat surface 188 L of the bottom of the board as in FIG. 36D; the bottom of the board may have only outer ridges in flat surface 184 L as depicted in FIG. 36A; the bottom of the board may have one central ridge and two outer ridges, as in FIG. 36B; the bottom of the board may have multiple sets of ridges as in FIG. 36 C.
Number of Ridges.
As indicated, the bottom surface can have one or more ridges.
Depth of Ridges.
The ridges can vary in depth, which is defined as the distance from the bottom-most edge to the uppermost point of the ridge. Described another way, looking at the cross-section “V” shape of a ridge, the depth would be measured from the bottom of the “V” to the top of the “V”.
Partial Ridge Coverage Longitudinally.
The ridges may extend the entire length of the board, from front to back, or they may extend over only a portion of the lengthwise distance. For example, a ridge could be only half the length of the board, starting from ¼ back from the leading edge and extending to ¾ back from the leading edge. Or a 2 inch ridge could be located close to the leading edge and another 3 inch ridge could be located back by the trailing edge.
Ridge Construction.
The ridges can be made of a material similar to the rest of the invention, or one or more ridges can consist of another material, or be constructed of multiple materials. Although the ridges would typically be constructed of a hard material, they may also be constructed of a flexible material. Ridges may have sharper, better-cutting edges by incorporation of a vertical blade made of metal or similar material.
Cross-Sectional Shape of Ridges.
The cross-sectional shape of the ridges as described in the preferred embodiment is triangular for the outer ridges and somewhat oval for the inner ridges. These shapes could be some other shape such as trapezoidal, rectangular, or curved (such as convex or concave-sided triangle or other polygon).
Angle of Protrusion of Ridges.
The angle of protrusion of the ridges in relationship to the tangent at the surface from which the ridges are protruding may be other than the preferred embodiment, which is perpendicular.
Ridges Placed on the Board for the Purpose of Turning.
Ridges may be used for turning. Ridges used for turning will preferably be placed on the periphery of a section and may vary in size, length, quantity, placement and construction.
Ridges Placed on the Board for the Purpose of Slowing or Stopping.
Ridges may be used for slowing and/or stopping. Ridges designed to slow or stop the board would preferably be placed in opposing pairs (one ridge turned to the left and one to the right), or as one or more ridges placed approximately perpendicular to the longitudinal axis of the section. They could be located on the periphery of the board, so that when the rider pushed the periphery down to engage the surface, the ridges would slow or stop the board. They could also be located elsewhere on the board and designed to drop down and engage when the rider's foot pressed an engagement mechanism.
Ridges Summarized.
In summary, ridges can be combined in a variety of ways, including varying uses, quantities, depths, lengths, angle, sharpness, shapes, location on board, construction, and composition.
Other Bottom Surface Additions for the Purpose of Increasing Friction.
A shape or material other than ridges can also be added to the bottom surface to increase friction under certain situations. This could be desirable, for example, on the far right or left side of the undersurface of the board, so that when that side of the board is tilted down, the friction on the side is increased, increasing drag and aiding in the turn towards that side. It may also be placed on the front or back of a section to improve braking action.
Removably Secured Bottom Surface Ridges or Additions. Ridges or bottom surface additions may be designed to be removable and/or changeable to allow users to customize the bottom surface of each section. For example, ridges set at a greater angle from the longitudinal axis would provide a rider with more extreme turning capabilities.
Bottom Platform Variations.
The platform that rides on the snow may be two ridges 180 L separated by a concave surface 183 L, as illustrated in FIG. 30 B. The ridges 180 L should be separated sufficiently so that the user may stand on a section and have the section supported in a stable non-tipping manner. A preferable separation should be between two and six inches with about three inches being preferred. Alternatively, the platform may be a flat surface 184 L as illustrated in FIG. 37A; or a single ridge 186 L embedded in a flat surface 185 L as illustrated in FIG. 37B; or a single ridge on a shallow, convex bottom as illustrated in FIG. 37 D.
Alternate Embodiments of the Connector.
Number Connectors.
More than one connector may be used to provide a less movable attachment between front and rear sections.
Dimensions of Connector.
The length and girth of the connector may vary. It could be as wide as the width of the front and back sections, or vary narrow. Although its length may be from approximately 2 inches to 5 inches long, it may be less that 2 inches or greater than 5 inches.
Non-Rigid Connector.
There may be situations where a non-rigid connector is preferred over a semi-rigid connector.
Alternate Embodiments of Springable Connector.
Metal Spring Plates Mounted on Each Section.
FIG. 38A, 38 B, 38 C, 38 D, 38 E, 38 F and 38 G illustrate a springable connection that uses an inflexible, non-springable rod 302 connected to a cylinder 301 L and 301 R. Speaking of the front section 340 L, flexible metal plates (such as a leaf spring) 304 and 305 provide a flexible, springable wall for the rod 302 to push against. The cylinder 301 L pivots within the reinforced area 303 which holds coil 306 . When turning to the left, the rod 302 would push against the metal plate 305 , forcing the coil 307 to travel away from the rod in a horizontal direction in open area 308 near trailing edge 359 . The same connection assembly is duplicated on the rear section of the present invention, providing a connection which has its ability to spring back and forth located within each section, rather than in the connector itself.
FIG. 39A, 39 B, 39 C, and 39 D illustrate a springable connector 455 made of horizontal metal plates. An upper metal plate 402 L and a lower metal plate 403 L, protruding from a block 450 L, mate with a center metal plate 405 . [t] The plates are held in place with a bolt 402 L, washers 404 and a locknut 414 L. The horizontal joint thus formed could also be created using other materials, such as a horizontal universal joint. A compression spring 401 is secured on the front side 407 L to a block 450 L and on the rear side 407 R to a block 450 R. Thus, a springable connection is created using a single joint and spring. Similarly, an upper metal plate 403 R and a lower metal plate 413 R protrude from block 450 R and also mate with a center metal plate 405 .
FIG. 39E and 39F illustrate a biased connection located on a front section 554 of the present invention having a leading edge 557 , a bottom 542 L and a trailing edge 559 . A spring 503 L is secured to a block 501 L which is secured to the top surface 540 L of the front section. Two metal plates 505 L which are secured to block 501 L mate to a rod or preferably inflexible metal plate 555 . The metal plate 555 is secured to metal plates 505 L with a bolt 504 L. A block 502 is secured to top surface 540 L to further control the spring 503 L. When the front section is turned left or right, the metal plate 555 moves horizontally, and is returned to its original position with the spring.
Summary of Alternate Embodiments of Springable Connector.
The connector of the preferred embodiment was continuously flexible and springable. In addition, the springable connector may consist of one or more inflexible segments, or it may be completely inflexible so that the flexibility is provided by its connection to the front and/or rear sections.
Alternate Embodiments of Materials of Construction.
The invention may be constructed of any number of appropriate materials, including carbon fiber, fiberglass, Kevlar, plastic, metal, wood, foam and composite. It is envisioned that commercial production may involve some type of injection or rotational molding.
Conclusions, Ramifications and Scope.
Accordingly, due to its two-piece articulated construction, the convex shape of the bottom of each section, the longitudinal ridges on the bottom surface, and the non-twisting, springable connector between the front and rear sections, this invention offers a rider capabilities not heretofore experienced.
The term “approximately convex” is used in the claims herein to mean largely convex, but also possibly including some flat or even slightly concave portion along a minor part of the lower surface.
Maneuverability, the key advantage of the present invention is made possible with the two-piece construction, the semi-rigid, springable connector and the shape of the bottom. Placement and type of ridges on the bottom provide for further options to change the performance characteristics of the board. When the ridges incorporate blades made of metal or similar material, the rider will be able to easily make controlled turns around even moguls.
The connector is constructed to made with a variety of sections, and sections can easily be interchanged, giving a rider a wide variety of performance choices. In addition, the rider can add, remove or move turning ridges, further increasing choices the invention can be easily dismantled into sections and connector for easy transport and storage.
The advantages of this invention over previous snow riding boards and skis are as follows:
Two-piece construction means increased maneuverability.
Convex bottom glides over and around bumps and moguls.
Longitudinal ridges provide maneuverability and control.
Ridges placed at any angle to the longitudinal access provide more aggressive turning capabilities.
Non-twisting, springable connector contributes to stability and control.
Interchangeable parts means more performance options for the rider at lower cost.
While the above-mentioned specifications are directed to a snowboard, the same structure and characteristics could be used in a waterboard or a board used to surf on sand.
Thus, the foregoing description is considered as illustrative only of the principles of the invention. Furthermore, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction and process shown as described above. Accordingly all suitable modifications and equivalents may be resorted to falling within the scope of the invention.
The present embodiments of this invention are thus to be considered in all respects as illustrative and not restrictive; the scope of the invention being indicated by the appended claims rather than by the foregoing description. All changes which come within the meaning and range of equivalency of the claims are intended to be embraced therein. | A two-piece articulated snowboard having a first section held to a second section by a connector. the connector is configured so that it permits some bending so that the longitudinal axis of the board bends at the connector. Preferably, the connector permits very little or no twisting so that the first and second sections stay in the same horizontal plane. | 0 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The field of the invention is magnetic resonance imaging (MRI) and, in particular, local coils for use in receiving MRI signals.
2. Background Art
A. Magnetic Resonance Imaging
In MRI, a uniform magnetic field B 0 is applied to an imaged object along the z-axis of a Cartesian coordinate system the origin of which is approximately centered within the imaged object. The effect of the magnetic field B 0 is to align the object's nuclear spins along the z-axis.
In response to a radio frequency (RF) excitation signal of the proper frequency, oriented within the x-y plane, the nuclei precess about the z-axis at their Larmor frequencies according to the following equation:
ω=γB.sub.0
where ω is the Larmor frequency, and γ is the gyromagnetic ratio which is constant and a property of the particular nuclei.
Water, because of its relative abundance in biological tissue and the properties of its nuclei, is of principle concern in such imaging. The value of the gyromagnetic ratio γ for water is 4.26 kHz/gauss and therefore, in a 1.5 Tesla polarizing magnetic field B 0 , the resonant or Larmor frequency of water is approximately 63.9 MHz.
In a typical imaging sequence for an axial slice, the RF excitation signal is centered at the Larmor frequency ω and applied to the imaged object at the same time as a magnetic field gradient G z is applied. The gradient field G z causes only the nuclei in a slice through the object along an x-y plane, to have the resonant frequency ω and to be excited into resonance.
After the excitation of the nuclei in this slice, magnetic field gradients are applied along the x and y axes. The gradient along the x axis, G x , causes the nuclei to precess at different frequencies depending on their position along the x axis, that is, G x spatially encodes the precessing nuclei by frequency. The y axis gradient, G y , is incremented through a series of values and encodes the y position into the rate of change of phase of the precessing nuclei as a function of gradient amplitude, a process typically referred to as phase encoding.
A weak nuclear magnetic resonance generated by the precessing nuclei may be sensed by the RF coil and recorded as an NMR signal. From this NMR signal, a slice image may be derived according to well known reconstruction techniques. An overview of NMR image reconstruction is contained in the book "Magnetic Resonance Imaging, Principles and Applications" by D. N. Kean and M. A. Smith.
B. Local Coils
The quality of the image produced by MRI techniques is dependent, in part, on the strength of the NMR signal received from the precessing nuclei. For this reason, it is known to use an independent RF receiving coil placed in close proximity to the region of interest of the imaged object to improve the strength of this received signal. Such coils are termed "local coils" or "surface coils". The smaller area of the local coil permits it to accurately focus on NMR signals from the region of interest. Further, the RF energy of the field of such a local coil is concentrated in a smaller volume giving rise to improved signal-to-noise ratio in the acquired NMR signal.
The signal-to-noise ratio of the NMR signal may be further increased by orienting two coils at 90° angles about the imaged object so that each detects RF energy along one of a pair of mutually perpendicular axes. This technique is generally known as quadrature detection and the signals collected are termed quadrature signals.
The outputs of the quadrature coil pairs are combined so as to increase the strength of the received signal according to the simple sum of the output signals from the coils. The strength of the uncorrelated noise component of these signals, however, will increase only according to the square root of the sum of the squares of the noise components. As a result, the net signal-to-noise ratio of the combined quadrature signals increases by approximately √2 over the signal-to-noise ratio of the individual signal.
The quadrature orientation of the two coils introduces a 90° phase difference between the NMR signals detected by these coils. Therefore, combining the outputs from the two quadrature coils, to achieve the above described signal-to-noise ratio improvement, requires that one signal be shifted to have the same phase as the other signal so that the amplitudes of the signals simply add.
Such phase shifting and combining is typically accomplished by means of a hybrid network. Hybrid networks are four-port networks known in the art and having the property that when the four ports are properly terminated, energy input to two of the ports, with the proper relative phase angles, will be combined at one of the remaining two ports. The antenna coils are attached to two of the ports and the output lead is attached to a third port. The remaining uncommitted port is connected to a termination resistor.
As used herein, the term quadrature coil and quadrature signal, will refer to the detecting of the NMR signal along multiple axes and combining the signals so collected, with the appropriate phase shifts to produce a signal of improved signal-to-noise ratio.
C. Bird Cage Coils
One method of constructing a local coil is the "bird cage" construction in which two conductive loops are spaced apart along a common longitudinal axis and interconnected by a series of regularly spaced longitudinal conductors. The impedance of the loops and of the longitudinal conductors is adjusted so that the coil may be excited into resonance by a rotating transverse magnetic field at the Larmor frequency. A quadrature signal may be obtained by monitoring the current through two longitudinal conductors spaced at 90° around the periphery of the loops. Such coils are described in detail in U.S. Pat. Nos. 4,680,548, 4,692,705, 4,694,255 and 4,799,016, hereby incorporated by reference.
When a bird cage coil is employed as a local coil, the diameter of the loops and the length of the segments are reduced, so that the volume within the bird cage conforms closely to the imaged part. For the imaging of human limbs, and particularly for the imaging of the knee, the bird cage structure is dimensioned so that its cylindrical volume conforms closely to the outer surface of the leg.
In practice, the smallest practical radius of the bird cage is rarely realized for the reason that it is desired that the coil be suitable for imaging other members besides the knee, such as the foot. Imaging of the foot is preferably done with the foot in the anatomical position essentially perpendicular to the axis of the leg. The radial extension of the toes in this position limits how small the radius of the loops of the bird cage coil may be.
For this reason, the signal-to-noise ratio of bird cage coils intended for multipurpose imaging, including imaging of both the knee and foot, is significantly less than may be obtained for a coil not used for imaging the foot.
SUMMARY OF THE INVENTION
The present invention provides a local bird cage coil suitable for imaging both the knee and foot yet having a signal-to-noise ratio better than that which would be obtained from a bird cage coil having a diameter substantially equal to the length of the foot.
Generally, the bird cage coil of the present invention includes one or more connecting segments having offset portions connected by transverse links, perpendicular to the longitudinal axis of the coil, to provide a small area into which the toes of the foot may extend without increasing the radius of the coil generally. It has been determined that this small extension region does not unacceptably affect the homogeneity of the sensitivity of the interior of the coil.
More particularly, the coil of the present invention is made up of a pair of conductive loops separated along a common longitudinal axis and defining a generally cylindrical volume. Longitudinally-oriented first conductive segments conforming generally to the surface of this volume electrically interconnect the loop elements at points spaced along the periphery of each loop. At least one second conductive segment electrically interconnects the loops but includes transversely extending portions which define a second volume outside of the generally cylindrical volume, that second volume receiving the toes of the foot.
It is thus one object of the invention to provide a local bird cage coil for imaging the foot and having an improved signal-to-noise ratio over a bird cage coil with a diameter large enough to accommodate the full length of a transversely oriented foot. The transverse portions on the second conductive segment allow the segment to accommodate the toes of the foot for a small portion of its length while generally preserving the structure of a bird cage coil of smaller radius and improved signal-to-noise ratio for the remainder of its extent.
The points of attachment of the first and second conductive segments to the end loops may be equally spaced around the end loops. It is thus another object of the invention to provide a bird cage coil of decreased radius suitable for imaging the foot, but without reducing the number of segments or adjusting the spacing of the segments both of which may decrease coil homogeneity.
Other objects and advantages besides those discussed above will be apparent to those skilled in the art from the description of the preferred embodiment of the invention which follows. Thus, in the description, reference is made to the accompanying drawings, which form a part hereof, and which illustrate one example of the invention. Such example, however, is not exhaustive of the various alternative forms of the invention. Therefore, reference should be made to the claims which follow the description for determining the full scope of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of the coil of the present invention devoid of obscuring support structure and padding showing the placement of a foot within a volume of the coil;
FIG. 2 is a cross-sectional view along lines 2--2 of FIG. 1 showing the configuration of one connecting segment which provides an appendant volume for the extension of the toes of the foot outside of the cylindrical volume defined by the end loops of the coil;
FIG. 3 is a schematic representation of the electrical characteristics of the coil of FIG. 1; and
FIG. 4 is a chart mapping lines of equal sensitivity of the coil of FIG. 1 along the plane of FIG. 2.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to FIG. 1, a local coil 10 constructed according to the present invention includes a first and second conductive end ring 12 and 14 spaced apart along a common longitudinal axis 16 to define a generally cylindrical volume 18 between the rings 12 and 14. The rings are electrically connected by a plurality of conductive segments 20 which extend in a direction parallel to the longitudinal axis and connect to the end rings 12 and 14 at points 22 which are spaced at equal angles around the periphery of rings 12 and 14.
The diameter of the rings 12 and 14 is such as to receive a human leg 24 through one ring 14, but so that only a portion of a foot 27 associated with the leg 24 is received within the volume 18 when the length of the foot extends transversely to the longitudinal axis 16. The toes of the foot 27 protrude beyond the volume 18.
Two segments 26, also connecting the end rings 12 and 14 at points 22', include longitudinal portions 28, 30 and 32 separated by transverse portions 34 and 36. Longitudinal portion 28 connects at one end to ring 14 at point 22' and at its other end to a transverse inner end of transverse portion 34. The transverse outer end of transverse portion 34 connects to longitudinal portion 30. Longitudinal portion 30, at its other end, connects to the transverse outer end of transverse portion 36. The transverse inner end of transverse portion 36 connects to one end of longitudinal portion 32 which then connects to point 22' of ring 12.
Each of the longitudinal and transverse portions 28 through 36 are straight but the segments 26 formed of the portions 28 through 36 has an outwardly extending section to avoid the toes of the foot 27 and thus to create an appendant volume 38. The appendant volume 38 is outside of the cylindrical volume 18, defined by the segments 20 and the end rings 12 and 14, and generally encompasses the toes of the foot 27. The appendant volume 38 is located on three sides by segments 30, 34 and 36.
It will be understood that although longitudinal portions 28, 30 and 32 of segment 26 are all parallel to the longitudinal axis 16, that longitudinal section 30 in fact is positioned further from the longitudinal axis 16 than segments 28 and 32, and that the latter segments 28 and 32 are the same distance from the longitudinal axis 16 as are the segments 20.
Referring to FIG. 3, the end rings 12 and 14 and the segments 20 and 26 are electrically conductive and electrically interconnected. Nevertheless, the impedance of each of these elements is not zero and must be adjusted to provide the necessary resonance of the local coil 10 near the Larmor frequency.
Referring to FIG. 3, the coil of FIG. 1 may be modeled as a ladder of interconnected inductances and capacitances representing the distributed impedance of the conductors forming the end rings 12 and 14 and the conductive segments 20 and 26.
In a so-called "low pass" configuration, the distributed inductance 19 of each ring 12 and 14, forming the "rails" of the ladder, is divided by the segments 20 and 26, forming the "rungs" of the ladder. The rungs have a net capacitive impedance provided by the insertion of small capacitors 21 along the length of the segments 20 or 26. The segments 20 and 26 also have an inductance 23 as a result of their physical extent, but this inductance 23, in the low pass configuration, is dominated by the added capacitance 21.
As modeled, it will be understood that this ladder resembles a delay line having input nodes 38 and output nodes 40, each being a corresponding pair of points on the rings 12 and 14, and that a voltage signal of a given frequency input at nodes 38 will be delayed in phase at nodes 40. Input and output nodes 38 and 40 are connected to each other in the formation of rings 12 and 14 and thus resonance can occur only when the values of the impedance of the end rings 12 and 14 and the segments 20 and 26 are such that a signal introduced at nodes 38 is phase shifted by a integer multiple of 360° at nodes 40. This phase shift accommodates the boundary conditions resulting from the connection together of nodes 38 and 40.
The selection of the values of the capacitors in the segments 20 and 26 will depend on the precise dimensions of the coil 10 but may be simply calculated for the Larmor frequency according to basic rules concerning electrical networks such as described. In distinction from a normal bird cage coil, however, because segments 26 are longer than segments 20, segments 26 will have a higher inductive value and thus will generally require greater values of accompanying capacitors 21. Specifically, for the embodiment shown, the value of the capacitors 21 will be selected according to the following formula: ##EQU1##
where X C21 is the value of capacitance 21, X L19 is the value of inductance 19, X L23 is the value of inductance 23 and θ is the angular separation among adjacent segments 22 and 26. As noted, for segments 26 the value of X L23 will generally be greater than the value of X L23 for segments 22.
As will be understood to those of ordinary skill in the art, other configurations of the coil 10 may also be adopted including "high pass" or "band pass" configurations in which capacitances are introduced in the end rings 12 and 14 instead of or in addition to those introduced into the segments 20 and 26. Of importance only is that the resonance of the coil 10 be tuned to the desired Larmor frequency and that the current through each segment 20 or 26, at any given time be sinusoidally related to the angle of that segment about the longitudinal axis 16 as it is attached to that ring 12 or 14.
Referring again to FIG. 1, this condition of sinusoidal dependance of the current through each segment 20 and 26 on the angular position of that segment about the rings 12 and 14 allows quadrature signals to be obtained by coupling signal leads 42 and 44 to the current through any two segments 20 or 26 displaced by 90° with respect to each other about the longitudinal axis 16. This coupling may be by any of a variety of methods known in the art including use of a tapping capacitor or an inductive pickup in proximity to that segment.
The coil 10 is preferably constructed of a plastic body (not shown) having a low dielectric value, over which are arranged strips of conductive foil which form the rings 12 and 14 and conductive segments 20 and 26. The capacitors 21 are positioned across small cuts in the foil as needed. A foam cushion 46 (shown in FIG. 3) may be placed within the volume 18 of the coil to provide a support for the leg 24 and to move the region of interest of the foot 27 into the region of the coil 10 having most uniform sensitivity. Guide rails (not shown) such as are well understood in the art serve to position the coil 10 within the larger bore of the MRI magnet.
Referring to FIG. 4, the deviation of the segments 26 does not significantly affect the uniformity of the sensitivity of the coil 10 in regions outside of the appendant volume 38 toward the center of the coil 10 where the region of interest of the foot 27 will be positioned.
The above description has been that of a preferred embodiment of the present invention. It will occur to those who practice the art that many modifications may be made without departing from the spirit and scope of the invention. For example, the rings need not be circular but may be slightly ellipsoidal to better accommodate the imaged limb. In order to apprise the public of the various embodiments that may fall within the scope of the invention, the following claims are made. | A radio frequency coil for receiving NMR signals in the imaging of a human foot includes a bird cage structure of longitudinally separated loops joined by longitudinal segments. Some of the segments include transverse portions which define an appendant volume for receiving the toes of the foot when the foot is placed in the coil with the leg generally longitudinal and the toes extending transversely. The appendant volume allows the average radius of the coil to be decreased with a corresponding increase in signal-to-noise ratio without unduly affecting the homogeneity of the coil's reception pattern. | 0 |
DESCRIPTION
[0001] The present invention relates to novel phosphine ligands, to their preparation and to their use in catalytic reactions, especially for refining halogenoaromatics.
[0002] Halogenoaromatics, including especially chloroaromatics, are intermediates which have a variety of applications in the chemical industry and are used as precursors for the preparation of agricultural intermediates, pharmaceuticals, dyestuffs, materials, etc. Vinyl halides are also important intermediates which are used as precursors for polymer monomers and the above-mentioned products.
[0003] Catalysts frequently used for the functionalization of halogenoaromatics or vinyl halides to give aromatic olefins or dienes (Heck reaction, Stille reaction), biaryls (Suzuki reaction), alkynes (Sonogashira reaction), carboxylic acid derivatives (Heck carbonylation) and amines (Buchwald-Hartwig reaction) are those of palladium and nickel. Palladium catalysts are generally advantageous in terms of the breadth of applicability of coupling substrates and in some cases the catalyst activity, while nickel catalysts have advantages in the area of the conversion of chloroaromatics and vinyl chlorides and the price of the metal.
[0004] Palladium and nickel catalysts used to activate and otherwise refine halogenoaromatics are palladium(II) and/or nickel(II) as well as palladium(0) and/or nickel(0) complexes, although it is known that palladium(0)/nickel(0) compounds are the actual reaction catalysts. In particular, according to literature sources, coordinatively unsaturated 14-electron and 16-electron palladium(0)/nickel(0) complexes stabilized with donor ligands such as phosphines are formulated as active species.
[0005] It is also possible to dispense with phosphine ligands when using iodides as educts in coupling reactions. However, aryl and vinyl iodides are very expensive starting compounds and moreover produce stoichiometric amounts of iodine salt waste. More cost-effective educts for the Heck reaction, such as aryl bromides or aryl chlorides, require the use of stabilizing and activating ligands in order to become effective in catalytic production.
[0006] The catalyst systems described for olefinations, alkynylations, carbonylations, arylations, aminations and similar reactions often have satisfactory catalytic turnover numbers (TONs) only with uneconomic starting materials such as iodoaromatics and activated bromoaromatics. Otherwise, in the case of deactivated bromoaromatics and especially in the case of chloroaromatics, it is generally necessary to add large amounts of catalyst—usually more than 1 mol %—to achieve industrially useful yields (>90%). In addition, because of the complexity of the reaction mixtures, simple catalyst recycling is not possible, so the recycling of the catalyst also incurs high costs, which are normally an obstacle to realization on the industrial scale. Furthermore, particularly in the preparation of active substances or active substance precursors, it is undesirable to work with large amounts of catalyst because of the catalyst residues left behind in the product. More recent active catalyst systems are based on cyclopalladized phosphines (W. A. Herrmann, C. Brossmer, K. Öfele, C.-P. Reisinger, T. Priermeier, M. Beller, H. Fischer, Angew. Chem. 1995, 107, 1989; Angew. Chem. Int. Ed. Engl. 1995, 34, 1844) or mixtures of sterically exacting arylphosphines (J. P. Wolfe, S. L. Buchwald, Angew. Chem. 1999, 111, 2570; Angew. Chem. Int. Ed. Engl. 1999, 38, 2413) or tri-tert-butylphosphine (A. F. Littke, G. C. Fu, Angew. Chem. 1998, 110, 3586; Angew. Chem. Int. Ed. Engl. 1998, 37, 3387) with palladium salts or palladium complexes.
[0007] However, even with these catalysts, cost-effective chloroaromatics cannot generally be activated satisfactorily from the industrial point of view, i.e. catalyst productivities (TONs) are <10,000 and catalyst activities (TOFs) are <1000 h −1 . Therefore, to achieve high yields, it is necessary to use comparatively large and hence very expensive amounts of catalyst. Thus, for example, the catalyst costs for the preparation of one kilogram of an organic intermediate with a molecular weight of 200, using 1 mol % of palladium catalyst, are more than 100 US$ at current noble metal prices, so there is clearly a need for improving catalyst productivity. Therefore, despite all the catalyst developments in recent years, only a few industrial reactions have so far been disclosed for the arylation, carbonylation, olefination etc. of chloroaromatics.
[0008] For the reasons mentioned, the object of the present invention was to satisfy the great. need for novel, more productive catalyst systems which have simple ligands and do not exhibit the disadvantages of the known catalytic processes, which are-suitable for the large industrial scale and which convert cost-effective chloroaromatics and bromoaromatics and corresponding vinyl compounds to the respective coupling products in high yield, with high catalyst productivity and with high purity.
[0009] This object is achieved according to the invention by the development of novel phosphine ligands of formulae Ia and Ib:
(adamantyl) n P(alkyl) m Ia
(adamantyl) o (alkyl) q P(alkylene′)P(adamantyl) r (alkyl) s Ib
[0010] in which adamantyl is an adamantyl radical (IIa, IIb) bonded to the phosphorus, atom. in the 1- or 2-position:
[0011] alkyl is a C 1 to C 18 alkyl group, and
[0012] alkylene′ is a bridging methylene, 1,2-ethylene, 1,3-propylene, 1,4-butylene, 1,5-pentylene or 1,6-hexylene bridge, 1,2-diphenylene, 2,2′-substituted 1,1′-binaphthyl or a ferrocenyl derivative,
[0013] where the alkyl group, the alkylene′ group and the adamantyl radical independently of one another can have, in addition to hydrogen atoms, up to 10 substituents which independently of one another are C 1 to C 8 alkyl, O-alkyl(C 1 -C 8 ), OH, OCO-alkyl(C 1 -C 8 ), O-phenyl, phenyl, aryl, fluorine, NO 2 , Si-alkyl(C 1 -C 8 ) 3 , CN, COOH, CHO, SO 3 H, NH 2 , NH-alkyl(C 1 -C 8 ), N-alkyl(C 1 -C 8 ) 2 , P(alkyl(C 1 -C 8 ) ) 2 , P(aryl) 2 , SO 2 -alkyl(C 1 -C 6 ), SO-alkyl(C 1 -C 6 ), CF 3 , NHCO-alkyl(C 1 -C 4 ), COO-alkyl(C 1 -C 8 ), CONH 2 , CO-alkyl(C 1 -C 8 ), NHCHO, NHCOO-alkyl(C 1 -C 4 )I CO-phenyl, COO-phenyl, CH═CH—CO 2 -alkyl (C 1 -C 8 ), CH═CHCOOH, PO(phenyl) 2 , PO(alkyl(C 1 -C 4 )) 2 , PO 3 H 2 , PO(O-alkyl (C 1 -C 6 )) 2 or SO 3 (alkyl(C 1 -C 4 )), aryl being an aromatic with 5 to 14 ring carbon atoms and it being possible for one or more ring carbon atoms to be replaced by nitrogen, oxygen and/or sulfur atoms to give a 1- to 13-membered heteroaromatic containing ring carbon atoms,
[0014] where n is a number between 1 and 3 and m is a number between 0 and 2, it being necessary to satisfy the condition n+m=3, and
[0015] where o and r are the number 1 or 2 and q and s are the number 0 or 1, it being necessary to satisfy the conditions o+q=2 and r+s=2.
[0016] The phosphine ligands used according to the invention are especially compounds of formulae Ia and Ib in which adamantyl is an adamantyl radical (IIa, IIb) bonded to the phosphorus atom in the 1- or 2-position and alkyl is a C 1 to C 12 alkyl group. Alkylene′ is preferably a bridging 1,2-ethylene, 1,3-propylene or 1,4-butylene bridge, 1,2-diphenylene, 2,2′-substituted 1,1′-binaphthyl or a ferrocenyl derivative.
[0017] Preferably, the alkyl group, the alkylene′ group and the adamantyl radical independently of one another can-have, in addition to hydrogen atoms, up to 5 substituents which independently of one another are C 1 to C 8 alkyl, O-alkyl(C 1 -C 8 ), OH, OCO-alkyl(C 1 -C 8 ), O-phenyl, phenyl, aryl, fluorine, Si-alkyl(C 1 -C 8 ) 3 , COOH, SO 3 H, NH 2 , NH-alkyl(C 1 -C 8 ), N-alkyl 2 (C 1 -C 8 ), P(alkyl(C 1 -C 8 )) 2 , P(phenyl) 2 , CF 3 , NHCO-alkyl(C 1 -C 4 ), COO-alkyl(C 1 -C 8 ), CONH 2 , CO-alkyl(C 1 -C 8 ), COO-phenyl, PO(phenyl) 2 , PO(alkyl(C 1 -C 4 )) 2 , PO 3 H 2 or PO(O-alkyl (C 1 -C 6 )) 2 , aryl being an aromatic with 5 to 14 ring carbon atoms and it also being possible for one or more ring carbon atoms to be replaced by heteroatoms from the group comprising nitrogen, oxygen and sulfur atoms to give a heteroaromatic with 4 to 13 ring carbon atoms.
[0018] Heteroaromatic radicals can be e.g. at least five-membered rings containing 1 to 13 ring carbon atoms and up to 4 nitrogen atoms and/or up to 2 oxygen or sulfur atoms. Preferred heteroaromatic-aryl radicals contain one or two nitrogen heteroatoms or one oxygen heteroatom or one sulfur heteroatom or one nitrogen heteroatom and one oxygen heteroatom or sulfur heteroatom.
[0019] Particularly preferred phosphine ligands according to the invention are compounds of formulae Ia and Ib in which adamantyl is an adamantyl radical (IIa, IIb) bonded to the phosphorus atom in the 1- or 2-position, alkyl is a C 1 to C 12 alkyl group and alkylene′ in formula Ib is a bridging 1,2-ethylene, 1,3-propylene or 1,4-butylene bridge, where the alkyl group, the alkylene′ group and the adamantyl radical independently of one another can have, in addition to hydrogen atoms, up to 3 substituents which independently of one another can be C 1 to C 8 alkyl, O-alkyl(C 1 -C 8 ), OH, OCO-alkyl(C 1 -C 8 ), O-phenyl, phenyl, COOH, SO 3 H, NH 2 , P(alkyl(C 1 -C 8 )) 2 , P(phenyl) 2 , COO-alkyl(C 1 -C 8 ), CONH 2 or PO (phenyl) 2 .
[0020] The invention also provides the preparation of the novel phosphine ligands. They are synthesized analogously to known preparative routes for alkylphosphines. Such synthetic pathways are described for example in Houben-Weyl, Methoden der organischen Chemie, 1963, volume XII, 1, p. 33. In general, the novel phosphine ligands described here are prepared by reacting a dihalogenoadamantyl-phosphine or halogenodiadamantylphosphine with metal-organic reagents (for example alkyllithium, alkylmagnesium, alkylzinc or alkylcopper reagents). Particularly suitable halogenoadamantylphosphines are the corresponding chlorine compounds. Another synthetic route for the preparation of the ligands according to the invention is to react alkali metal adamantylphosphides or alkali metal diadamantylphosphides with organic electrophiles such as alkyl halides or pseudohalides, aldehydes or epoxides.
[0021] In general, diadamantylalkylphosphines can be synthesized according to the following instructions: A solution of 18 mmol of R-M in THF or hexane is added dropwise to a solution of 15 mmol of diadamantylchloro-phosphine in 250 ml of absolute THF, M being lithium or MgHal and Hal being chlorine, bromine or iodine. The mixture is refluxed for two hours. It is worked up at room temperature with degassed aqueous ammonium chloride solution and diethyl ether. The solvents are distilled off and the residue is distilled under high vacuum or chromatographed on silica gel 60 with hexane/ethyl acetate mixtures.
[0022] These instructions can be used to prepare e.g. the following preferred ligands:
[0023] di(1-adamantyl)methylphosphine,
[0024] di (1-adamantyl)-i-propylphosphine,
[0025] di(1-adamantyl)-n-butylphosphine,
[0026] di(1-adamantyl)-t-butylphosphine,
[0027] di(1-adamantyl)-n-hexylphosphine,
[0028] di(1-adamantyl)cyclohexylphosphine,
[0029] di(1-adamantyl)benzylphosphine,
[0030] di(1-adamantyl)pentafluoroethylphosphine,
[0031] di(3-aminoadamant-1-yl)-n-butylphosphine,
[0032] di(3-acetyladamant-1-yl)-n-butylphosphine,
[0033] di[3-(p-hydroxyphenyl)adamant-1-yl]methylphosphine,
[0034] di(2-adamantyl)-i-propylphosphine,
[0035] di(2-adamantyl)-n-butylphosphine,
[0036] di(2-adamantyl)-t-butylphosphine,
[0037] di(2-adamantyl)cyclohexylphosphine.
[0038] In general, adamantyldialkylphosphines can be synthesized according to the following instructions: A solution of 15 mmol of a dialkylchlorophosphine in THF is added dropwise to a solution of 35 mmol of adamantyl-M in 400 ml of absolute THF or hexane, M being lithium or MgHal and Hal being chlorine or bromine. The mixture. is refluxed for four hours. It is worked up at room temperature with degassed aqueous ammonium chloride solution and diethyl ether. The solvents are distilled off and the residue is distilled under high vacuum or chromatographed on, silica gel 60 with hexane/ethyl acetate mixtures.
[0039] These instructions can be used to prepare e.g. the following preferred ligands:
[0040] (1-adamantyl)di-t-butylphosphine,
[0041] (1-adamantyl)dicyclohexylphosphine,
[0042] (2-adamantyl)di-n-butylphosphine.
[0043] In general, bis(diadamantylphosphino)alkanes can be synthesized according to the following instructions: A solution of 15 mmol of M-alkylene-M in THF or hexane is added dropwise to a solution of 33 mmol of diadamantyl-chlorophosphine in 400 ml of absolute THF, M being lithium or MgHal and Hal being chlorine, bromine or iodine. The mixture is refluxed for four hours. It is worked up at room temperature with degassed aqueous ammonium chloride solution and diethyl ether. The solvents are distilled off and the residue is distilled under high vacuum-or chromatographed on silica gel 60 with hexane/ethyl acetate mixtures.
[0044] These instructions can be used to prepare e.g. the following preferred ligands:
[0045] 1,2-bis[di(l-adamantyl)phosphino]ethane,
[0046] 1,4-bis[di(l-adamantyl)phosphino]butane,
[0047] 2,3-bis[di(l-adamantyl)phosphino]butane,
[0048] 4,5-bis[di(l-adamantyl)phosphinomethyl]-2,2-dimethyl-1,3-dioxolane,
[0049] 1,2-bis[di(l-adamantyl)phosphino]benzene.
[0050] According to the invention, the novel phosphine ligands are used as catalysts in combination..with transition metal complexes or transition metal salts of subgroup VIII of the Periodic Table of the Elements, for example palladium, nickel, platinum, rhodium, iridium, ruthenium or cobalt. As a rule, the ligands according to the invention can be added in situ to appropriate transition metal precursor compounds and used in this form for catalytic applications.
[0051] The transition metal compounds used are preferably palladium or nickel compounds and particularly preferably palladium compounds.
[0052] It may be advantageous on occasion to prepare defined mono-, di-, tri- or tetraphosphine complexes of said transition metals first and then use these for catalytic. reactions.
[0053] It is preferable to use palladium and nickel catalysts containing the phosphines according to the invention.
[0054] It is particularly preferable to use palladium catalysts containing the ligands according to the invention. The ligands according to the invention are normally added in situ to palladium(II) salts or to palladium(II) or palladium(0) complexes. However, it may be advantageous to prepare palladium(0)—or palladium(II)-phosphine complexes of the phosphines according to the invention direct and then use these for catalytic applications. This increases the initial catalyst activity in some instances.
[0055] Examples of palladium components that can be used with the ligands according to the invention are palladium(II) acetate, palladium(II) chloride, palladium(II) bromide, lithium tetrachloropalladate (II), palladium (II) acetylacetonate, palladium(0)-dibenzylidenacetone complexes, palladium(0) tetrakis(triphenylphosphine), palladium(0) bis(tri-o-tolylphosphine), palladium(II) propionate, palladium(II) bis(triphenylphosphine) dichloride, palladium(0)-diallyl ether complexes, palladium(II) nitrate, palladium(II) chloride. bis(acetonitrile), palladium(II) chloride bis(benzonitrile) and other palladium(0) and palladium(II) complexes.
[0056] Generally, for catalytic applications, the phosphine ligand is used in excess relative to the transition metal. The ratio of transition metal to ligand is preferably from 1:1 to 1:1000. Ratios of transition metal to ligand of 1:1 to 1:100 are particularly preferred. The exact transition metal/ligand ratio to be used depends on the specific application and also on the amount of catalyst used. Thus, in general, it is conventional to use low transition metal/ligand ratios in the case of very low transition metal concentrations (<O.01 mol %) than in the case of transition metal concentrations of between 0.5 and 0.01 mol % of transition metal.
[0057] The novel phosphine ligands are thermally very stable. It. is thus possible to use the catalysts according to the invention at reaction temperatures of up to 250° C. or more. The catalysts are preferably used at temperatures of 20 to 200° C.; it has proved advantageous in many cases to work at temperatures of 30 to 180° C., preferably of 40 to 160° C. The ligands can also be used in pressure reactions without loss of activity, the operating pressure conventionally being up to only 100 bar, but preferably in the normal pressure range of up to 60. bar.
[0058] The phosphine ligands prepared according to the invention have proved particularly advantageous as ligand components for the catalytic preparation of arylated olefins (Heck reactions), biaryls (Suzuki reactions), α-aryl ketones and amines from aryl halides or vinyl halides. However, it is obvious to those skilled in the art. that other transition metal-catalyzed reactions, such as the metathesis or hydrogenation of double bonds or carbonyl compounds, especially however palladium-catalyzed and nickel-catalyzed carbonylations of aryl halides, alkynylations with alkynes (Sonogashira couplings) and cross couplings with metal-organic reagents (zinc reagents, tin reagents, etc.), can also be catalyzed with the novel catalyst systems.
[0059] For some catalytic applications, for example carbonylations, it may be advantageous to use chelating phosphine ligands, particularly important chelating phosphine ligands being those with an aliphatic C 2 to C 6 carbon bridge or with an aromatic bridge (1,2-phenylene, ferrocenyl, binaphthyl).
[0060] One particular advantage of the ligands according to the invention is the high activity which the ligands induce in the activation of cost-effective but inert chloroaromatics. As shown in the experimental Examples, palladium catalysts with the novel adamantylphosphines are significantly superior to the best existing catalyst systems of Buchwald (J. P. Wolfe, S. L. Buchwald, Angew. Chem. 1999, 111, 2570; Angew. Chem. Int. Ed. Engl. 1999, 38, 2413) and Fu (A. F. Littke, G. C. Fu, Angew. Chem. 1998, 110, 3586; Angew. Chem. Int. Ed. Engl. 1998, 37, 3387). Thus, with the catalyst systems according to the invention, it is even possible to achieve turnover numbers in the order of >10,000 with chloroaromatics as substrates and TONs of >500,000 with bromoaromatics as starting materials, making the described catalyst and ligand systems useful for large-scale industrial purposes.
[0061] The properties of the adamantylphosphines are particularly surprising. Although adamantyl radicals have been known for a long time in organic chemistry, no importance has been attached to phosphine ligands containing adamantyl groups. Consequently, alkyladamantylphosphines have not hitherto been described for catalytic applications. It was surprising to find that, in certain catalytic applications, adamantyl ligands are significantly superior to all other known phosphine ligands. For example, whereas the product yields obtained in the coupling of 4-chlorotoluene with an arylboronic acid using small amounts of catalyst (0.005 mol %) are 16 to 46% with the best palladium catalysts known hitherto, yields of >90% were obtained with the ligands according to the invention.
[0062] The phosphines prepared according to the invention can be used for the preparation of arylolefins, dienes, diaryls, benzoic acid derivatives, acrylic acid derivatives, arylalkanes, alkynes and amines. The compounds prepared in this way can be used inter alia as UV absorbers, intermediates for pharmaceuticals and agrochemicals, ligand precursors for metallocene catalysts, perfumes, active substances, and structural units for polymers.
EXAMPLES
[0063] The Examples which follow serve to illustrate the invention without implying a limitation.
[0064] General: The adamantylphosphine ligands are prepared under a protective gas (argon).
[0065] General instructions for synthesis of the phosphines:
[0066] A mixture of 100 g (0.73 mol) of adamantane, 105 g (0.79 mol) of aluminium(III) chloride and 300 ml of phosphorus(III) chloride was refluxed for 5 h. The excess phosphorus(III) chloride was distilled off to leave a reddish-brown viscous substance. This was suspended in 1 1 of chloroform and then hydrolyzed with 1 1 of ice-water. The organic phase was dried over sodium sulfate and concentrated to dryness under vacuum (0.1 mbar). Yield: 130 g (0.37 mol, 93%) of di(1-adamantyl)phosphinyl chloride (melting point: 195° C.).
[0067] 40 g of diadamantylphosphinyl chloride (0.11 mol) were placed in 600 ml of absolute tetrahydrofuran, the mixture was cooled to −14° C. with an ice-water/sodium chloride cooling mixture, and 10 g (0.26 mol) of lithium aluminium hydride were added in successive portions over 60 min. The mixture was then stirred at room temperature for 16 h and hydrolyzed at −14° C. with 200 ml of 1 N HCl solution. The organic phase was dried over sodium sulfate and concentrated to dryness under vacuum (0.1 mbar). Yield: 30 g (0.10 mol, 94%) of di(l-adamantyl)phosphine.
[0068] [0068] 31 P NMR (162.0 MHz, CDCl 3 ): δ=18.2
[0069] 60 g of a 20% solution of phosgene in absolute toluene were added dropwise at −14° C. to a solution of 23 g (76 mmol) of di(1-adamantyl)phosphine and 14.5 g (9.5 mmol) of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in 600 ml of toluene and the mixture was heated to room temperature and then stirred for 16 h. It was filtered and the solvent was distilled off under vacuum. Yield: 23 g (68 mmol, 90%) of diadamantylchlorophosphine.
[0070] [0070] 31 P NMR (162.0 MHz, CDCl 3 ): δ=138.4
Example 1
[0071] Di (1-adamantyl)-n-butylphosphine (n-BuPAd 2 ) (Variant 1):
[0072] 11 ml of a 1.6 M solution of n-butyllithium in hexane (18 mmol) were added dropwise to 5.0 g (15 mmol) of diadamantylchlorophosphine in 250 ml of absolute tetrahydrofuran. The solution was refluxed for 1 h. After removal of the solvent under vacuum, the residue was distilled under vacuum.
[0073] 2.6 g (7.3 mmol, 49%) of diadamantyl-n-butylphosphine were obtained.
[0074] Di(1-adamantyl)-n-butylphosphine (n-BuP(1-Ad) 2 ) (Variant 2):
[0075] 4.6 g (15 mmol) of di(1-adamantyl)phosphine were placed in 50 ml of di-n-butyl ether, and 20 ml of a 2.5 M solution of n-BuLi in toluene (50 mmol) were added. The mixture was refluxed for 1 h and cooled and 4.1 g (30 mmol) of 1-butyl bromide were added dropwise. The mixture was refluxed for 30 min, cooled and washed with saturated ammonium chloride solution (3×), the organic phase was separated off and dried over sodium sulfate and the solvent was distilled off under reduced pressure.
[0076] Yield: 4.6 g (13 mmol, 85%) of di(1-adamantyl)-n-butylphosphine. The product can be recrystallized from di-n-butyl ether (m.p.: 102° C.).
[0077] [0077] 31 P{ 1 H} NMR (162.0 MHz, C 6 D 6 , 297 K): δ=24.6
[0078] MS (E. I., 70 eV):. m/z: 358 (M + , 12%); 135 (Ad + , 100%)
[0079] MS (C.I., isobutene): m/z: 359 (M + +H, 100%)
[0080] Di(1-adamantyl)-n-butylphosphine (n-BuP(1-Ad) 2 ) (Variant 3):
[0081] 1.5 g (4.5 mmol) of di(1-adamantyl)chlorophosphine were placed in 40 ml of absolute THF, and 5.ml of a 1.6 M solution of n-BuLi in hexane (8 mmol) were added using a syringe, with stirring. The mixture was refluxed for 2 h, the solvent was distilled off under reduced pressure and the residue was distilled in a bulb tube. Yield: 0.77 g (2.1 mmol, 48%) of di(1-adamantyl)-n-butylphosphine.
[0082] Di(1-adamantyl)-n-butylphosphine (n-BuP(1-Ad) 2 ) (Variant 4):
[0083] 4.6 g (15 mmol) of di(1-adamantyl)phosphine were placed in 50 ml of di-n-butyl ether, and 20 ml of a 2.5 M solution of n-BuLi in toluene (50 mmol) were added. The mixture was refluxed for 1 h and cooled and 2.8 g (30 mmol) of 1-butyl chloride were added dropwise. The mixture was refluxed for 30 min, cooled and washed with saturated ammonium chloride solution (3×), the organic phase was separated off and dried over sodium sulfate and the solvent was distilled off under reduced pressure. The product was purified by bulb tube distillation under fine vacuum. Yield: 4.6 g (13 mmol, 85%) of di(1-adamantyl)-n-butylphosphine.
Example 2
[0084] Di(1-adamantyl)methylphosphine (MeP(1-Ad) 2 ) (Variant 1):
[0085] 11 ml of a 1.6 M solution of methyllithium in hexane (18 mmol) were added dropwise to 5.0 g (15 mmol) of diadamantylchlorophosphine in 250 ml of absolute tetrahydrofuran. The solution was refluxed for 1 h. After distillation of the solvent under vacuum, the residue was distilled under vacuum.
[0086] 2.3 g (7.3 mmol, 49%) of diadamantylmethylphosphine were obtained.
[0087] Di(1-adamantyl)methylphosphine (MeP(1-Ad)2) (Variant 2):
[0088] 2.0 g (6.0 mmol) of di(1-adamantyl)chlorophosphine were placed in 50 ml of absolute THF, and 5 ml of a 1.6 M solution of MeLi in diethyl ether (8 mmol) were added using a syringe, with stirring. The mixture was refluxed for 2 h, the solvent was distilled off under reduced pressure and the residue was distilled in a bulb tube. Yield: 0.85 g (2.7 mmol, 45%) of di(1-adamantyl)methylphosphine (m.p.: 143° C.).
[0089] Elemental analysis: found (calc.): C: 79.52% (79.70%); H: 10.60% (10.51%); P: 9.78% (9.79%)
[0090] [0090] 31 P{ 1 H} NMR (162.0 MHz, C 6 D 6 , 297 K): δ=7.8
[0091] MS (E.I., 70 eV): m/z: 316 (M + , 36%); 135 (Ad + , 100%)
Example 3
[0092] Di(1-adamantyl)-n-hexylphosphine (HexP(1-Ad) 2 ) (Variant 1):
[0093] 0.45 g of magnesium turnings (18 mmol) was placed in 150 ml of absolute tetrahydrofuran, and 3.0 g of 1-bromohexane (18 mmol) were added, with stirring, causing the ether to warm up. After the mixture had-cooled to room temperature, a solution of 5.0 g of diadamantylchlorophosphine (15 mmol) in 100 ml of absolute tetrahydrofuran was added dropwise and the mixture was refluxed for 1 h. After distillation of the solvent under vacuum, the residue was distilled under high vacuum (0.01 mbar). Yield: 2.0 g (5.2 mmol, 35%) of diadamantyl-n-hexylphosphine.
[0094] Di(1-adamantyl)-n-hexylphosphine (HexP(1-Ad)2) (Variant 2):
[0095] 5.5 g (18 mmol) of di(1-adamantyl)phosphine were placed in 60 ml of di-n-butyl ether, and 20 ml of a 2.5 M solution of n-BuLi (50 mmol) in toluene were added. The mixture was refluxed for 45 min and cooled and 3.0 g (18 mmol) of 1-bromohexane were added dropwise. The mixture was refluxed for 30 min, cooled and washed with saturated ammonium chloride solution (3×), the organic phase was separated off and dried over sodium sulfate and the solvent was distilled off under reduced pressure.
[0096] Yield: 4.9 g (13 mmol, 70%) of di(l-adamantyl)-n-hexylphosphine. The product can-be recrystallized from di-n-butyl ether.
[0097] [0097] 31 P{ 1 H} NMR (162.0 MHz, C 6 D 6 , 297 K): δ=24.6
[0098] MS: 386.31062 (calc. for C 26 H 43 P: 386.31024)
Example 4
[0099] Bis (diadamantylphosphino) butane (butylene (PAd 2 ) 2):
[0100] 0.45 g of magnesium turnings (18 mmol) was placed in 150 ml of absolute tetrahydrofuran, and 2.0 g of 1,4-dibromobutane (9.3 mmol) were added, with stirring, causing the ether to warm up. After the mixture had cooled to room temperature, a solution of 5.0 g of diadamantylchlorophosphine (15 mmol) in 100 ml of absolute tetrahydrofuran was added dropwise and the mixture was refluxed for 1 h. After distillation of the solvent under vacuum, the residue was distilled under high.vacuum (0.01 mbar). Yield: 1.0 g (1.5 mmol, 10%) of bis(diadamantylphosphino)butane.
Example 5
[0101] Di(1-adamantyl)-3-dimethylaminopropylphosphine:
[0102] 5.1 g (17 mmol) of di(1-adamantyl)phosphine were placed in 50 ml of di-n-butyl ether, and 20 ml of a 2.5 M solution of n-BuLi (50 mmol) in toluene were added. The mixture was refluxed for 1 h and cooled and 5.0 g (31 mmol) of 3-dimethylaminopropyl chloride hydrochloride were added, with cooling in an ice bath. The mixture was refluxed for 30 min, cooled and washed with saturated ammonium chloride solution (3×), the organic phase was separated off and dried over sodium sulfate and the solvent was distilled off. under reduced pressure. Yield: 4.6 g (12 mmol, 70%) of di(1-adamantyl)-3-dimethylaminopropylphosphine. The product can be recrystallized from di-n-butyl ether (m.p.: 138° C.).
[0103] Elemental analysis: found (calc.): C: 77.46% (77.47%); H: 11.09% (10.92%); N: 3.47% (3.61%); P: 7.78% (7.99%)
[0104] [0104] 31 P{ 1 H} NMR (162.0 MHz, C 6 D 6 , 297 K): δ=24.5
[0105] MS: 387.30528 (calc. for C 25 H 42 NP: 387.30548)
Example 6
[0106] Di (1-adamantyl)benzylphosphine:
[0107] 4.0 g (13 mmol) of di(1-adamantyl)phosphine were placed in 50 ml of di-n-butyl ether, and 18 ml of a 2.5 M solution of n-BuLi (45 mmol) in toluene were added. The mixture was refluxed for 30 min and cooled and 3.2 g (19 mmol) of benzyl bromide were added dropwise. The mixture was refluxed for 30 min, cooled and washed with saturated ammonium chloride solution (3×), the organic phase was separated off and dried over sodium sulfate and the solvent was distilled off under reduced pressure. Yield: 4.6 g (12 mmol, 90%) of di(1-adamantyl)benzylphosphine. The product is recrystallized from di-n-butyl ether (m.p.: 182° C.)
[0108] [0108] 31 P{ 1 H} NMR(162.0 MHz, C 6 D 6 , 297 K): δ=29.8
[0109] MS: 392.26420 (calc. for C 27 H 37 P: 392.26328)
Examples 7 to 20
[0110] General Operating Instructions for the Heck Reaction:
[0111] In a pressure tube (obtainable e.g. from Aldrich), 5 mmol of aryl halide, 6 mmol of olefin, 6 mmol of base, a suitable amount of ligand and palladium(0)-dba complex and 500 mg of diethylene glycol di-n-butyl ether (as internal standard for GC analysis) were added to 5 ml of absolute dioxane under an argon atmosphere. The tube was sealed and suspended in a silicone oil bath at 120° C. After 24 h it was left to cool to room temperature. The solids were dissolved in 5 ml of methylene chloride and 5 ml of 2 N hydrochloric acid. The organic phase was analyzed by gas chromatography. The products were isolated by distillation, crystallization from methanol/acetone mixtures or column chromatography (silica gel, hexane/ethyl acetate mixtures).
TABLE 1 Heck reaction of p-chlorotoluene and styrene; n-BuPAd 2 as ligand Temp. Cat. conc. Conversion Yield No. Base (° C.) (mol %) L:Pd (%) (%) TON 7 K 3 PO 4 100 1.0 1:1 42 38 38 8 K 3 PO 4 100 1.0 2:1 39 25 25 9 K 3 PO 4 120 0.1 2:1 27 20 200 10 K 3 PO 4 120 1.0 2:1 98 98 98 11 K 3 PO 4 120 0.1 4:1 25 11 110 12 K 2 CO 3 120 1.0 2:1 78 68 68 13 K 3 PO 4 140 0.1 4:1 88 81 810
[0112] [0112] TABLE 2 Heck reaction of chlorobenzene and styrene at 120° C.; L:Pd = 2:1 Cat. conc. Conversion Yield No. Base (mol %) (%) (%) TON 14 K 2 CO 3 1.0 71 63 63 15 K 3 PO 4 2.0 46 33 17
[0113] [0113] TABLE 3 Heck reaction with 2-ethylhexyl acrylate at 120° C.; base: K 3 PO 4 ; 2.0 mol% of Pd (dba) 2 ; L:Pd = 2:1 No. Aryl chloride Ligand Conversion (%) Yield (%) TON 16 n-BuPAd 2 66 63 32 17 n-BuPAd 2 94 82 41 18 n-BuPAd 2 51 34 17 19 n-BuPAd 2 38 12 6 20 n-BuPAd 2 48 44 22
Examples 21 to 40
[0114] General Operating Instructions for the Suzuki Reaction:
[0115] In a pressure tube (obtainable e.g. from Aldrich), 3 mmol of aryl halide, 4.5 mmol of phenylboronic acid, 6 mmol of base, a suitable amount of ligand and palladium(II) acetate (P:Pd=2:1) and 100 mg of hexadecane (as internal standard for GC analysis) were dissolved in 6 ml of absolute toluene under an argon atmosphere. The tube was sealed and suspended in a-silicone oil bath at 100° C. After 20 h it was left to cool to room temperature. The solids were dissolved in 10 ml of methylene chloride and 10 ml of dilute sodium hydroxide solution. The organic phase was analyzed by gas chromatography. The products were isolated by crystallization from methanol/acetone mixtures or column chromatography (silica gel, hexane/ethyl acetate mixtures).
TABLE 4 Influence of the ligand on the coupling of 4-chlorotoluene and phenylboronic acid No. PR 3 Pd(OAc) 2 (mol %) Yield (%) TON 21 PPh 3 0.1 5 50 22 PhPCy 2 0.1 23 230 23 [a] (o-tol) PCy 2 0.1 49 490 24 [a] (o-anisyl) PCy 2 0.1 42 420 25 (o-biph) PCy 2 0.01 47 4700 26 PCy 3 0.1 23 230 27 PtBu 3 0.01 92 9200 28 P t Bu 3 0.005 41 8200 29 BuPAd 2 0.01 94 9400 30 BuPAd 2 0.005 87 17,400
[0116] [0116] TABLE 5 Suzuki coupling of various aryl chlorides (R-C 6 H 4 —Cl) with phenylboronic acid in the presence of 0.005 mol % of Pd(OAc) 2 /2 BuPAd 2 No. R Yield (%) TON 31 4-Me 87 17,400 32 [a] 4-Me 74 14,800 33 2-Me 85 17,000 34 2,6-Me2 68 13,600 35 H 80 16,000 36 2-F 96 19,200 37 4-MeO 64 12,800 38 3-MeO 58 11,600 39 2-CN 100 20,000 40 “3-N,” [b] 99 19,800
Examples 41 to 54
[0117] General Operating Instructions for Catalytic Amination:
[0118] In a pressure tube (obtainable e.g. from Aldrich), 5 mmol of aryl halide, 6 mmol of amine, 6 mmol of sodium tert-butylate and a suitable amount of ligand and palladium(0)-dibenzylidenacetone complex were added to 5 ml of absolute toluene under an argon atmosphere. The tube was sealed and suspended in a silicone oil bath at 120° C. After 20 h it was left to cool to room temperature. The solids were dissolved in 5 ml of CH 2 Cl 2 and 5 ml of 2 N hydrochloric acid, and 500 mg of diethylene glycol di-n-butyl ether were added as internal GC standard. The organic phase was analyzed by gas chromatography. The products were isolated by distillation, crystallization from methanol/acetone mixtures or column chromatography (silica gel, hexane/ethyl acetate mixtures).
TABLE 6 Catalytic amination of aryl halides; 0.5 mol % of Pd(dba) 2 , n-BuPAd 2 Yield No. Aryl chloride Amine Product [%] 41 2-chloro- 2, 6- bis(2,6-dimethyl- 84 m-xylene dimethylaniline phenyl) amine 42 2-chloro- 2,6-diiso- 2,6-dimethylphenyl- 70 m-xylene propylaniline 2′,6′-diisopropyl- aniline 43 2-chlorofluoro- 2,6-diiso- 2-fluorophenyl- 70 benzene propylaniline 2′,6′-diisopropyl- aniline 44 2-chloro- 1-adamantyl- N-(1-adamantyl)- 84 m-xylene amine 2,6-dimethylaniline 45 2-chloro- tert-butylamine N-(tert-butyl)-2,6- 93 m-xylene dimethylamine 46 chlorobenzene diethylamine N,N-diethylaniline 44 47 chlorobenzene di-n-butylamine N,N-di-n- 72 butylaniline 48 3-chlorotoluene diethylamine N,N-diethyl-m- 49 toluidine 49 3-chloroanisole diethylamine N,N-diethyl-m- 58 methoxyaniline 50 4-chlorotoluene diethylamine N,N-diethyl-p- 40 toluidine 51 chlorobenzene piperidine N-phenylpiperidine 76 52 chlorobenzene morpholine N-phenylmorpholine 87 53 o-chloroanisole 2,6-dimethyl- 2-methoxyphenyl- 100 aniline 2,6-dimethylaniline 54 o-chloroanisole 2,6-diiso- 2-methoxyphenyl- 88 propylaniline 2,6-diisopropyl- aniline
Examples 55 to 59
[0119] Catalytic α-arylation of Ketones:
[0120] In a pressure tube (obtainable e.g. from Aldrich), 5 mmol of aryl halide, 6 mmol of ketone, 6 mmol of sodium tert-butylate and a suitable amount of ligand and palladium(II) acetate were added to 5 ml of absolute toluene under an argon atmosphere. The tube was sealed and suspended in a silicone oil bath at 80° C. After 20 h it was left to cool to room temperature. The solids were dissolved in 5 ml of CH 2 Cl 2 and 5 ml of 2 N hydrochloric acid, and 500 mg of diethylene glycol di-n-butyl ether were added as internal GC standard. The organic phase was analyzed by gas chromatography. The products were isolated by distillation, crystallization from methanol/acetone mixtures or column chromatography (silica gel, hexane/ethyl acetate mixtures).
TABLE 7 Catalytic α-arylation of ketones; 1 mol % of PdOAc 2 ; 2 mol % of n-BuPAd 2 Con- T version No. Aryl-X (20 C.) Ketone (%) 55 120 100 chloro- aceto- benzene phenone 56 80 66 p- deoxy- chloro- benzoin toluene 57 80 99 p- propio- chloro- phenone toluene 58 80 100 p- 3- chloro- pentan- toluene one 59 80 100 1,2-di- 3- chloro- pentan- benzene one Product 1 Product 2 (mono- Yield a ) (bis- Yield a ) arylated) (%) arylated) (%) 70 28 deoxy- diphenyl- benzoin methane ./. 65 1,2- diphenyl- 2-p- tolyl- ethanones 97 ./. 1-phenyl- 2-p- tolyl- propan-1- ones 54 not isolated no data 2-p- tolyl- pentan-3- ones 58 not isolated no data 2-(2′- chloro- phenyl)- pentan-3- ones
Examples 60 to 79
[0121] Further Catalysis Examples of the α-arylation of Ketones:
[0122] In a pressure tube (obtainable e.g. from Aldrich), 5 mmol of aryl halide, 6 mmol of ketone, 6 mmol of tripotassium phosphate and a suitable amount of ligand and palladium(II) acetate were added to 5 ml of absolute dioxane under an argon atmosphere. The tube was sealed and suspended in a silicone oil bath at 100° C. After 20 h it was left to cool to room temperature. The solids were dissolved in 5 ml of CH 2 Cl 2 and 5 ml of 2 N hydrochloric acid, and 500 mg of diethylene glycol di-n-butyl ether were added. as internal GC standard. The organic phase was analyzed by gas chromatography. The products were isolated by distillation, crystallization from methanol/acetone mixtures or column chromatography (silica gel, hexane/ethyl acetate mixtures).
TABLE 8 Reaction of chlorobenzene with acetophenone; 1 mol% of PdOAc 2 No. Ligand Temp. Conversion (%) Yield (%) of
deoxybenzoin Yield (%) of
1,2,2- triphenyl- ethanone 60 100 83 16 51 BuPAd 2 61 100 68 6 44 N,N-dimethyl- aminopropyl- PAd 2 62 100 72 31 31 phenyl-PCy 2 63 100 74 33 32 PCy 3 64 100 50 17 19 o-biphenyl-PCy 2 65 100 31 17 3 BuPCy 2 66 100 37 0 19 P(t-Bu) 3 67 100 44 9 20 Bup(t-Bu) 2 68 100 17 2 0 PPh 3
[0123] [0123] TABLE 9 α-Arylation of ketones; 1 mol % of PdOAc 2 ; 2 mol % of n-BuPAd 2 Con- T version No. Aryl-X (° C.) Ketone (%) 69 100 83 chloror- aceto- benzene phenone 70 100 100 p- deoxy- chloro- benzoin toluene 71 120 100 100 48 p- propio- chloro- phenone toluene 72 100 100 p- 1- chloro- indan- toluene one 73 100 42 p- 3- chloro- pentan- toluene one 74 100 100 p- cyclo- chloro- hexan- toluene one 75 100 100 p- aceto- chloro- phenone anisole Product 1 Product 2 (mono- Yield a (bis- Yield a arylated) (%) arylated) (%) 16 51 deoxy- 1,2,2- benzoin tri- phenyl- ethanone ./. 100 1,2- diphenyl- 2-p- tolyl- ethanones 90 38 ./. 1-phenyl- 2-p- tolyl- propan-1- ones 42 32 2-p- 2,2- tolyl-1- bis(p- indanone tolyl)-1- indanone 27 not no data 2-p- isolated tolyl- pentan-3- ones 38 ./. 2-p- tolyl- cyclo- hexanones 25 57 2-p- 2,2-bis- anisyl-1- p-anisyl- phenyl- 1-phenyl- ethanones ethanone
Example 80
[0124] Coupling of Aryl Chlorides with Organozinc Compounds:
[0125] 50 mmol of anhydrous zinc chloride (dissolved in 40 ml of THF) were added at 0° C to a suspension of 50 mmol of ethynyllithium-ethylenediamine complex in 40 ml of THF. After heating to RT for half an hour, the solution was again cooled to 0° C. and 40 mmol of 4-chloroanisole, 0.05 mol % of Pd(OAc) 2 and 0.1 mol % of butyldiadamantylphosphine were added. The reaction mixture was stirred at 25 to 50° C. until conversion was complete. 2 M HCl solution was then added to the reaction solution. After extraction with ether, washing of the ether phase and distillation, 76% of p-methoxyphenylacetylene is obtained.
Example 81
[0126] Coupling with Alkynes:
[0127] 0.005 mol % of Pd(OAc) 2 , 0 .01 mol % of hexyldiadamantyl-phosphine and 1 mol % of Cu(I)I are added to a mixture of 12 mmol of trimethylsilylacetylene and 10 mmol of 4-chloronitrobenzene in 40 ml of diethylamine. The mixture is stirred under reflux until conversion is complete. The readily volatile constituents are then removed under vacuum. The residue is dissolved in toluene and washed with water. After chromatography on silica gel, 89% of 1-(4-nitrophenyl)-2-trimethylsilylacetylene is obtained.
Example 82
[0128] Heck Coupling with Ethylene:
[0129] 50 mmol of 6-methoxy-2-bromonaphthalene and 60 mmol of potassium carbonate are dissolved in 40 ml of NMP, and 0.001 mol % of Pd(OAc) 2 and 0.004 mol % of butyldiadamantyl-phosphine are added. The mixture is placed under an ethylene pressure of 20 bar and stirred at 130° C. until conversion is complete. After filtration of the insoluble constituents, washing with alkaline solution and distillation, 92% of 6-methoxy-2-vinylnaphthalene is obtained.
Example 83
[0130] Carbonylation Reaction:
[0131] 20 mmol of 6-methoxy-2-bromonaphthalene and 30 mmol of triethylamine are dissolved in 30 ml of 1-butanol, and 0.05 mol % of Pd(OAc) 2 and 0.1 mol % of butyldiadamantylphosphine are added. The mixture is placed under a CO pressure of 3 bar and stirred at 130° C. until conversion is complete.
[0132] After filtration of the insoluble constituents, washing with alkaline solution and distillation, 94% of butyl 6-methoxy-2-naphthalenecarboxylate is obtained. | The invention relates to novel phosphane ligands of formula (Ia) and (Ib): (adamantyl)nP(alkyl)m(1a); (adamantyl)o(Alkyl)qP (alkylen′)P(adamantyl)r(alkyl)s (1b), wherein adamantyl represents an adamantyl radical (IIa, IIb) bonded to the phosphorous atom in position 1 or 2. The invention also relates to the production and use of the above-mentioned ligands in the presence of transitional metal compounds of the 8th. Subgroup of PSE for catalytic reactions, particularly for the refining of halogen aromatics for producing aryl olefins, dienes, diarylene, benzoic acid and acrylic acid derivatives, aryl alkanes and also amines. | 2 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention is directed to a multiple electrode unitary intravascular catheter designed for use in a system which continually monitors heart function and, upon detection of abnormal function, provides either pacing energy or cardioverting energy as required. The unitary intravascular catheter is in one or more ways more versatile, more compact or more easily implanted than previous multiple electrode systems capable of functioning in the same modes. Additionally, the unitary catheter, which comprises a distal electrode, an intermediate electrode, and a proximal electrode, provides superior sensing capability immediately following cardioversion as compared to the prior art two-electrode catheters. Where a modified cardioverting energy distribution is required, the single intravascular catheter may be used in conjunction with other electrodes, such as a patch electrode applied to the external surface of the heart.
2. Description of the Prior Art
During the past several decades, coronary heart disease has become the primary cause of death in the developed areas of the world. Close to 1.5 million Americans will suffer a heart attack this year, with nearly 350,000 of them dying suddenly following the myocardial infarction. Although the precise cause of sudden death in coronary heart disease has not yet been entirely clarified, the available evidence permits the medical field to ascribe death in the majority of sudden death cases to rapid disturbances in cardiac electrical activity known as tachyarrhythmia. Tachyarrhythmic heart conditions which may be lethal, are ventricular tachycardia, ventricular flutter, and ventricular fibrillation. Atrial tachyarrhythmic conditions such as atrial tachycardia and fibrillation only become life threatening when they lead to rapid ventricular disturbance.
Excessively slow rhythm disturbances, known as bradyarrhythmias, are involved in a minority of cases. Bradyarrhythmic conditions become serious when there is a defect in impulse formation or in the normal cardiac conduction system without adequate "escape" rhythm.
Within the hospital environment, recent experience has demonstrated that tachyarrhythmic conditions are often reversible phenomena and may be corrected by applying relatively high energy electrical shocks to the heart. Bradyarrhythmic conditions, although not as often fatal, are often correctable by pacemaking pulses of very low energy. The correction of arrhythmic heart conditions by application of relatively high energy electrical shock to the heart will, for the purposes of this invention, be referred to as "cardioversion".
In recent years, substantial progress has been made in the development of techniques for effectively terminating various tachyarrhythmias. Recent developments include implantable electronic standby defibrillators which, in response to the detection of an abnormally rapid cardiac rhythm, discharge sufficient energy via electrodes connected to the heart to depolarize and restore the heart to normal cardiac rhythm.
Considerable sophistication now exists with regard to techniques for reliably monitoring heart activity in order to determine whether cardioversion is necessary. Included among such techniques are those which monitor ventricular rate to determine the presence of fibrillation on the basis of a probability density function (PDF), a technique described in commonly owned U.S. Pat. Nos. 4,184,493 and 4,202,340, both of Langer et al, and a more recent system which is disclosed in commonly owned co-pending application Ser. No. 175,670 of Langer et al, filed Aug. 5, 1980, now abandoned, utilizing both the PDF technique to determine the presence of an abnormal cardiac rhythm and a heart rate sensing circuit for distinguishing between ventricular fibrillation and high-rate tachycardia, on the one hand, and a normal sinus rhythm or low-rate tachycardia, on the other hand.
Commonly owned, co-pending application Ser. No. 478,038 of Imran et al, filed Mar. 23, 1983, discloses a cardioversion system including an implantable defibrillator and an external non-invasive controller/monitor for altering the state and/or retrieving status information from the implanted defibrillator. The implantable defibrillator comprises a high-voltage inverter circuit with shunt-prevention means; a combination of a PDF circuit and a heart-rate analysis circuit, each circuit detecting abnormal cardiac rhythms and both circuits jointly activating the high-voltage inverter circuit; a plurality of electrodes connected to the heart, including bipolar sensing electrodes, coupled with the heart-rate analysis circuit, for sensing ventricular activity; high-voltage pulse delivery electrodes, coupled with the high-voltage inverter circuit; circuits for, respectively, delivering high-energy, defibrillating pulses, and providing PDF information signals; a pulse counter/memory for counting and storing the number of defibrillating pulses issued by the inverter circuit; a piezoelectric speaker, coupled to the wall of a case enclosing the defibrillator circuits, for generating audible tones indicative of the status of the defibrillator; and means responsive to an external magnet for changing the state of the defibrillator.
Technology now exists for the development of implantable devices capable of both pacing and cardioverting, each in response to a sensing mechanism which is incorporated in the implantable device. The electrodes for sensing cardiac electrical abnormalities, as well as for delivering electrical impulses to the heart, are an extremely important consideration in the entire pacing/cardioverting system. U.S. Pat. No. 3,942,536 to Mirowski et al discloses a single intravascular catheter electrode system which monitors heart function and provides the malfunctioning heart with electrical shocks of sufficient amplitude to restore the heart to normal sinus rhythm.
U.S. Pat. No. 4,030,509, issued to Heilman et al, discloses several embodiments of an electrode system for use in ventricular defibrillation wherein the electrodes are applied to the exterior surface of the heart.
U.S. Pat. No. 4,161,952, issued to Kinney et al, discloses a catheter electrode including a resilient, wound wire discharge electrode having proximal and distal ends. The proximal end of the lead is adapted for connection to a pulse generator. The lead is connected to the wound wire discharge electrode both at the proximal and distal ends thereof, and the catheter electrode system is designed for positioning in the superior vena cava or in the coronary sinus, and preferably acts against an independent apex electrode. Thus, the electrode system of Kinney et al is not of unitary design.
U.S. Pat. No. 4,355,646, issued to Kallok et al, discloses a lead having multiple electrodes which is intravenously implanted for use in patients having a high risk of ventricular fibrillation. The lead comprises four electrodes, the two distal electrodes being spaced for optimal measurement of impedance changes due to mechanical contractions and used for mechanical sensing of normal cardiac activity. The two proximal electrodes are spaced from the distal electrodes so as to ensure their placement within the superior vena cava; the two distal electrodes serve to deliver the defibrillation energy.
None of the prior art references noted above discloses an effective multiple electrode unitary intravascular catheter capable of sensing heart abnormality and delivering either defibrillating energy or pacing energy in response to the abnormality for restoring normal heart function.
Additionally, none of the prior art devices noted above is capable of delivering a high-energy discharge through a single catheter and immediately being able to effectively sense the heart's electrical activity through the same catheter. Following cardioversion, the tissue in the area immediately adjacent the discharge electrodes at least temporarily loses a substantial portion of its ability to conduct electrical impulses due to the high electrical energy just applied to the area. Full recovery most often results, but there is a time when electrical conduction suffers. This phenomenon deleteriously impacts on the sensing capability of the prior art devices which sense and cardiovert from the same two electrodes, at least at a time when sensing is of utmost importance.
Further, the prior art electrodes were somewhat limited in their capability for integration with other electrodes in the event that pacing, cardioverting, or sensing could more effectively be accomplished through alternate electrode configurations.
Thus, a need has continued to exist for a unitary multiple electrode catheter capable of sensing, pacing and cardioverting the heart, with an improved sensing capability immediately following cardioversion, and having the flexibility to permit integration with other electrodes in the event that a more effective distribution of the electrical energy is attainable.
SUMMARY OF THE INVENTION
It is an object of this invention to provide a multiple electrode unitary catheter.
It is another object of this invention to provide a multiple electrode unitary catheter which can be intravascularly positioned.
It is still an object of this invention to provide a multiple electrode unitary catheter capable of sensing, pacing, and cardioverting heart abnormalities.
It is a further object of the instant invention to provide a multiple electrode unitary catheter capable of accurately sensing heart activity immediately following cardioversion.
It is yet an object of the instant invention to provide a multiple electrode unitary catheter capable of integration with a patch electrode by replacement of one of the cardioverting electrodes with the patch electrode where better energy distribution is required.
These and other objects as will hereinafter become more apparent are accomplished by a unitary multiple electrode catheter comprising a distal electrode, an intermediate electrode and a proximal electrode, heart rate sensing and pacing being provided by the distal electrode in combination with the intermediate electrode and PDF sensing and cardioversion being provided by the intermediate electrode in combination with the proximal electrode.
The instant catheter provides continued, accurate sensing of heart rate activity following cardioversion because it utilizes different electrodes and an advanced electrode placement; therefore, different heart tissue is involved in the rate sensing activity on the one hand and the cardioverting activity on the other hand.
Further, because the instant catheter is compact and yet very versatile, it can be combined with other electrodes simply by changing a connection at the pulse generator.
These and other advantages of the invention will become more readily apparent when reference is made to the following description taken in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side view of the multiple electrode unitary intravascular pacing, cardioverting, and sensing catheter of the present invention.
FIG. 1a is an enlarged fragmentary cross section of that portion of FIG. 1 between the distal tip and the line 1a--1a.
FIG. 1b is an enlarged fragmentary cross-sectional view of that portion of FIG. 1 between lines 1a--1a and 1b--1b.
FIG. 1c is an enlarged fragmentary cross-sectional view of that portion of FIG. 1 between lines 1b--1b and 1c--1c.
FIG. 1d is an enlarged fragmentary view of that portion of FIG. 1 between lines 1c--1c and 1d--1d.
FIG. 1e is an enlarged fragmentary cross-sectional view of that portion of FIG. 1 showing elements 80, 86 and 86a.
FIG. 1f is an enlarged fragmentary cross-sectional view of that portion of FIG. 1 showing element 102.
FIG. 1g is an enlarged fragmentary cross-sectional view of that portion of FIG. 1 showing element 101.
FIG. 1h is an enlarged fragmentary cross-sectional view of that portion of FIG. 1 showing element 91.
FIG. 1i is an enlarged fragmentary cross-sectional view of that portion of FIG. 1 showing element 90.
FIG. 2 is a cross-sectional view depicting the catheter of the present invention positioned in the heart.
FIG. 3 is a cross-sectional view of an embodiment wherein the unitary intravascular catheter is used in conjunction with an external patch electrode.
DESCRIPTION OF THE PREFERRED EMBODIMENT
The following description refers to FIGS. 1 and 1a through 1i of the drawings, hereinafter referred to collectively as "FIG. 1", where there is illustrated a plan view of a multiple electrode unitary catheter for sensing, cardioverting, and pacing comprising a distal electrode 10, an intermediate electrode 18, and a proximal electrode 48. Distal electrode 10 comprises a distal tip 12 and lead 14, said lead 14 providing electrical conductivity between distal tip 12, via element 91 (FIG. 1h), through heart lead coil 98, and terminating at male plug 96. Distal tip 12 has a diameter in the range of 2.0-2.8 mm, a length in the range of 0.5-2.0 mm, and a surface area on the order of about 10-20 mm 2 . Typically, the distal tip is constructed of a platinum, iridium alloy containing approximately 10% iridium. Distal electrode 10, in conjunction with intermediate electrode 18, provides sensing and pacing functions.
The electrical conductor 98 (FIG. 1h) of lead 14 (FIG. 1a) is encased by an insulating tubing such as of Silastic, said insulating tubing typically having an outside diameter of 1.07 mm and an inside diameter of 0.81 mm. Lead coil 98 terminates in male plug 96, adapted for insertion into an implantable device, not shown.
Distal electrode 10 is separated from intermediate electrode 18 by tubing 16. Tubing 16 acts to hold the distal tip in place, to seal the internal catheter from the body fluids, to provide proper spacing between distal electrode 10 and intermediate electrode 18, and to electrically insulate distal electrode 10 from intermediate electrode 18. Typically, tubing 16 takes the form of a suitable insulating tubing such as Silastic having a wall thickness defined by an outside diameter in the range of 1.8-2.8 mm and an inside diameter in the range of 1.8-2.0 mm. One critical aspect in the electrode of this invention lies in the spacing between distal electrode 10 and intermediate electrode 18. It is preferred that the spacing between these two electrodes lies in the range of 1 to 10 mm. An optimal distance between the two electrodes is 4 mm.
Intermediate electrode 18 comprises lead fittings 20 and 22, spring 23, said spring 23 comprising an electrically conductive wound wire surface, two electrically conductive tubings 28 and 30, said two electrically conductive tubings 28 and 30 connected in parallel, DBS wires 40, 92 and 100, and male plugs 94 and 104 (see FIGS. 1i and 1g). Lead fittings 20 and 22 and spring wire 23 comprise an electrically conductive material inert to body fluids. C. P. titanium or platinum coated C. P. titanium is a preferred material for this utility. Lead fitting 20 provides electrical contact between electrically conductive surface 23 and electrically conductive tubing 28; lead fitting 22 provides electrical contact between electrically conductive surface 23 and electrically conductive tubing 30. Spring 23 has a length in the range of about 20 to 50 mm and a diameter in the range of about 3.0 to 4.0 mm. This spring is close-wound, and is preferably wound to approximately 20 turns per inch. The close-wound spring provides a continuous electrically conductive surface which maintains its flexibility while still lowering the impedance of the electrode and thus permitting more current to be delivered. Typically, the surface area for intermediate electrode 18 is in the range of about 30 to 50 mm 2 , with about 43 mm 2 being the preferred surface area. Another important aspect of the present invention involves the length of the intermediate electrode 18 as measured from the outside edges of lead fittings 20 and 22. It is preferred that this length be in the range of about 20 to 50 mm, with about 38 mm being optimal. Insulative tubing 36 typically comprises a Silastic material, having an outside diameter of about 2.8 mm and an inside diameter of about 2.4 mm. Tubing 36 provides insulative separation between conductive lead fittings 20 and 22 and, additionally, seals the internal catheter from body fluids. Electrically conductive tubings 28 and 30 are made of an electrically conductive material, typically stainless steel, and provide electrical contact between DBS wire 40 and lead fittings 20 and 22. DBS wire 40 is drawn, brazed, stranded wire, typically a mixture of stainless steel and silver, and provides means for electrical transmission for intermediate electrode 18. Thus, intermediate electrode 18, acting through spring element 23, provides sensing, pacing, and cardioverting capability, coacting with distal electrode 10 to provide sensing and pacing and coacting with proximal electrode 48 to provide sensing and cardioversion.
Tubing 46 is typically an insulating tubing, such as Silastic, typically having an outside diameter of 3.2 mm and an inside diameter of 2.0 mm and serves to electrically insulate intermediate electrode 18 from proximal electrode 48, seal the internals of the catheter from body fluids, provide sufficient flexibility in the catheter to provide for proper insertion and prevent perforation of the heart. Additionally, tubing 46 provides for proper spacing between intermediate electrode 18 and proximal electrode 48. It is preferred that this distance be in the range of about 8 to 14 centimeters, with about 11 centimeters being optimal.
Proximal electrode 48 (FIG. 1c) comprises lead fittings 50 and 52, spring 53, said spring 53 comprising an electrically conductive wound wire surface, electrically conductive tubings 58 and 60, tubing 66, DBS wire 68, DBS wire 70, and male plug 108 (FIG. 1f). Lead fittings 50 and 52, and spring 53 comprise electrically conductive materials which are inert to body fluids. Typically, these elements are made of C. P. titanium, platinum, iridium, or platinum coated titanium. Electrically conductive tubings 58 and 60 are typically stainless steel and are connected in parallel by DBS wire 68. It is contemplated that proximal electrode 48, as measured from the outside edges of lead fittings 50 and 52, be in the range of about 5 to 10 cm, with approximately 7.5 cm being optimal, and have a diameter in the range of about 3.0 to 4.0 mm. Proximal electrode 48, acting through spring 53 and male plug 108, and paired with intermediate electrode 18, provides cardioverting means as well as PDF sensing means. DBS wires 68 and 70 are drawn, brazed, stranded wire, typically a mixture of stainless steel and silver, and provide electrical connection between male plug 108, adapted for insertion into an implantable electrical device for sensing pacing and cardioverting, and spring 53.
Elements 80, 86 and 86a are reinforcing members. Element 82 is a splice and provides for integration of DBS wire 92 and DBS wire 100. After integration, these two wires become DBS wire 40 (FIG. 1b). Elements 84a and 84b are typically insulating tubing such as Silastic, typically having an outer diameter of about 3 mm and an inner diameter of about 2 mm. Elements 88a, 88b, 88c and 88d are typically insulating tubing such as Silastic, typically having an outer diameter of about 1.95 mm and an inner diameter of about 1.25 mm. Each of these tubing elements electrically insulates its respective lead and protects it from body fluids. Elements 90, 91, 101 and 102 are proximal boots and provide for adaptive insertion and sealing, respectively, of the male plugs 94, 96, 104 and 108 into the implantable electrical device. Similar devices are described in U.S. Pat. No. 4,262,673. One of the male plugs 94, 96, 104, and 108, in a manner known to the prior art, is hollow and thus adapted for insertion of a stylette, the stylette facilitating directional control of the catheter during its placement in the heart.
The three-electrode catheter of the present invention represents a substantial advance over prior art catheters. Because heart rate sensing and pacing are accomplished by the distal electrode in conjunction with the intermediate electrode, while higher energy cardioversion is accomplished by the intermediate electrode in conjunction with the proximal electrode, the instant catheter maintains its capability for heart rate sensing and low threshold pacing following cardioversion. Because the at least temporary depolonization of heart tissue due to higher voltage cardioversion affects heart tissue different from that involved with the rate sensing and pacing functions, the catheter continues to perform its rate sensing and low threshold pacing on undamaged heart tissue.
Referring now to FIG. 2, there is depicted one possible position of the catheter electrode system of the present invention in a heart for effecting ventricular defibrillation. Distal electrode 10, comprising distal tip 12, and intermediate electrode 18 is wedged in the apex of the right ventricle. Proximal electrode 48 is in the right atrium and superior vena cava, straddling their junction.
FIG. 3 shows one embodiment of the present invention wherein the intravascular catheter is positioned as in FIG. 2 and, additionally, the heart is fitted with an external patch electrode.
In certain situations, the unitary catheter system will not function to provide the required cardioverting energy and an additional external patch electrode 120 is required. Typical external patch electrodes are described in commonly assigned U.S. Pat. No. 3,942,536. Patch electrode 120 comprises the patch 122, the patch lead 124, said patch lead 124 terminating in a proximal boot 101' and male plug 104', male plug 104' insertable into the implantable device in place of male plug 104.
In operation, it is contemplated that the anesthetized patient has the catheter system intravascularly inserted into the heart, for example, as in FIG. 2. At this point, fibrillation is induced in order to test the functioning of the system and to provide information regarding threshold energy requirement levels. If the single catheter system is insufficient, the patient is fitted with a patch electrode 120. At the same time, male plug 104 is disengaged from the implantable device and sealed to prevent penetration by body fluids. Male plug 104' is inserted into the implantable device to provide bipolar defibrillation through patch electrode 120 and proximal electrode 48, inserted into the implantable unit through male plug 108. By disengaging and sealing male plug 104, only the defibrillating characteristic of intermediate electrode 18 is affected. The pacing and sensing function of intermediate electrode 18 remains intact, connection to the implantable device occurring through male plugs 94 and 96.
Having now fully described the invention it will be apparent to one of ordinary skill in the art that many changes and modifications can be made thereto without departing from the spirit and scope of the invention as set forth herein. | A multiple electrode unitary intravascular cardiac catheter comprising a distal electrode for sensing and pacing, an intermediate electrode for sensing, pacing and cardioverting, and a proximal electrode for sensing and cardioverting. The catheter may also be employed in combination with an external patch electrode. | 0 |
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims the benefit of U.S. Provisional Application No. 61/804,471, filed Mar. 22, 2013. The disclosure of the above application is incorporated herein by reference
FIELD OF THE INVENTION
The present invention is directed to a window attachment system suited for selectively connecting removable windows to a foldable roof of a foldable, stowable roof.
BACKGROUND OF THE INVENTION
Foldable stowable roof tops are commonly used in sport-utility vehicles for recreational purposes. The foldable roof is typically moved between a stowed position, and a deployed position. When in the deployed position, the foldable roof protects the occupants of the vehicle from various weather conditions. The foldable roof also includes various sections which are made of a clear material to essentially function as a window, allowing the occupant of the vehicle to see outside of the vehicle. It is also sometimes desirable to open these clear window sections when weather conditions are favorable, but the occupant(s) of the vehicle may not desire to change the foldable roof to the stowed position.
Because these window sections are also foldable and/or removable, typical window crank devices and electric motors used for opening and closing a window made of glass (which is rigid and not foldable) are not suitable for use with a foldable roof. Therefore, other methods of opening the foldable window have been developed.
One of these methods is a zipper which is typically one continuous zipper that surrounds all sides of the window but one. The one side of the window which is not surrounded by the zipper is the foldable side, allowing the window to be folded from the closed to the open position. One of the drawbacks to this type of design is that typical zippers are designed for connecting two sheets of material along a substantially straight surface. These zippers are difficult to align and misalignment results in higher zipper effort. In addition, both sides of the zipper are in the same plane and the difference between the radius of the outer window connected to the zipper and the radius of the foldable roof connected to the zipper is typically the width of the zipper. This makes the zipper difficult to use around the corners of the window because there is an imbalanced amount of stress placed on the portion of the zipper connected to the window and the portion of the zipper connected to the foldable roof. Another one of the drawbacks is that the window is not removable, which necessitates clear, foldable, window sections that must be folded and secured out of the way taking up space within the vehicle and can create noise from vibrating in the wind when the vehicle is moving.
Another of these methods for opening the window is employing a removable window. Current soft windows are attached to the soft top via zippers. These prove to be quite cumbersome to use. It is difficult to align the zipper end into the box end of the corresponding zipper on the soft top. Secondly, the zipper can be difficult to close and/or open as the efforts can be quite high due to zipper misalignment between the soft top and window assembly. This is caused by manufacturing issues and/or tolerances such as in alignment during the sewing process that is used to attach the zippers to the soft top and windows. Misalignment can cause the zipper teeth to skip thereby making the zipping motion efforts high. Any variation of the zipper alignment can result in higher zipper efforts around at least the upper rear corner where the curved portion of the window is connectable to the roof resulting in installation difficulty of the window. Another issue from zipper teeth skipping and/or misalignment of zipper halfs is that this can cause the window to not be closed all the way resulting in gaps where water and air can enter the vehicle.
Accordingly, there exists a need for removable windows including zipper less attachments which are suitable for providing a selective connection between a foldable roof and the removable windows having various straight and curved areas.
SUMMARY OF THE INVENTION
The present invention is directed to a zipper less removable window assembly having window attachment devices for eliminating zippers for use with a foldable, stowable roof for a vehicle, where the foldable roof includes one or more removable windows made of a plastic material such as polyvinyl chloride (PVC). The window attachment devices are easier to use and reduce the stress/effort caused by conventional zippers which are difficult to operate.
The foldable, stowable roof is connected to a vehicle, and has at least one curved portion and at least one straight portion. Additionally, the removable window is also connected to the vehicle, and the removable window has at least one curved portion and at least one straight portion. The curved portion of the foldable, stowable roof generally corresponds to the shape of the curved portion of the removable window. The removable window comprises a plurality of attachment devices selectively connecting the foldable, stowable roof to the removable window. Each of the plurality of attachment devices is zipper less and has a first half connected to the foldable, stowable roof and a second half connected to the removable window. The plurality of window attachment devices connect the left side quarter window, right side quarter window, and rear window to the vehicle and the foldable, stowable roof.
Further areas of applicability of the present invention will become apparent from the detailed description provided hereinafter. It should be understood that the detailed description and specific examples, while indicating the preferred embodiment of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
The present invention will become more fully understood from the detailed description and the accompanying drawings, wherein:
FIG. 1 is an elevation view of a first half of a zipper on a deck side strip connected to a foldable roof used for a window;
FIG. 2 is an elevation view of a second half of the zipper connected to a quarter window used for connecting the window to the deck side strip/foldable roof of FIG. 1 ;
FIG. 3 is a perspective view of the first half of the zipper of FIG. 1 connected to the second half of the zipper of FIG. 2 along a straight portion;
FIG. 4 is a rear side perspective view of a curved portion of the quarter window and the foldable roof of FIGS. 1-3 showing the zipper as it nears the curved portion as the zipper is zipped closed;
FIG. 5 is a schematic for a vehicle incorporating zipper less removable windows, for selectively connecting a foldable roof and removable windows, according to the present invention;
FIG. 6 is an enlarged sectional view taken along section A-A of FIG. 5 , according to the present invention;
FIG. 7 is an enlarged sectional view taken along section B-B of FIG. 5 , according to the present invention;
FIG. 8 is an enlarged sectional view taken along section C-C of FIG. 5 , according to the present invention;
FIG. 9 is a schematic for the vehicle of FIG. 5 incorporating zipper less removable quarter and rear windows, for selectively connecting a foldable roof and the removable windows showing additional cross sections, according to the present invention;
FIG. 10 is an enlarged sectional view taken along section D-D of FIG. 9 , according to the present invention;
FIG. 11 is an enlarged sectional view taken along section E-E of FIG. 9 , according to the present invention;
FIG. 12 is an enlarged sectional view taken along section F-F of FIG. 9 , according to the present invention;
FIG. 13 is a rear right side perspective view of a rear window carrier slid onto a rear deck valance, according to the present invention;
FIG. 14 is a front side perspective view of a quarter window carrier slid onto the deck side strip, according to the present invention; and
FIG. 15 is a rear left side perspective view of an installed rear window and a quarter window connected to the foldable roof, according to the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The following description of the preferred embodiment(s) is merely exemplary in nature and is in no way intended to limit the invention, its application, or uses.
Referring generally to FIGS. 1-4 , a typical zipper, shown generally at 10 , is connected to a deck side strip/foldable roof 12 and a window 14 , e.g., a quarter window. Such conventional windows with zippers are problematic. The zipper 10 can be connected to the foldable roof 12 and the window 14 by a first seam of a first half 16 and can be connected to the window 14 through the use of a second seam of a second half 18 . The zipper start location is critical in relation to the corresponding start on the window and yet variation is common such as at least +/−10 millimeters of variation. This is caused by sewing tolerances during manufacturing and other manufacturing issues. In addition, the placement of the zipper 10 on the deck side strip is critical to the corresponding zipper half on the window 14 and yet variation is common such as at least +/−10 millimeters of variation. Another issue with typical zipper systems is that the alignment of the zipper to the quarter window 14 can vary, such as at least +/−5 millimeters of variation, and does not align perfectly with a “V” notch indicator in the window fabric reinforcement. In particular, there is misalignment with the second seam/zipper and the concentric window fabric reinforcement in the corner area of the window 14 . FIG. 1 illustrates a conventional first half 16 of a zipper on a foldable roof 12 having a zipper start location that can vary by at least +/−5 mm from the edge. FIG. 2 illustrates a conventional second half 18 of a zipper on a window 14 having a zipper start location that can vary by at least +/−5 mm.
FIG. 3 illustrates installation of the window 14 zipper start into the deck side box end of the foldable roof 12 . This can be difficult, compounded by the variations and misalignment of these features, resulting in the zipper teeth to skipping, thereby making the zipper 10 motion efforts high. Further, any variations of the zipper manufacturing alignment can result in high zipper 10 efforts around the corner portions, e.g., around the upper rear corner depicted in FIG. 4 , shown generally at 20 , resulting in installation difficulty of the window 14 .
Referring generally to FIGS. 5-15 , there is provided a zipper less removable window assembly, shown generally at 100 , connected to a vehicle 11 . The zipper less removable window assembly 100 includes a plurality of removable windows, shown generally at 102 , having a plurality of window attachments, where the plurality of removable windows 102 includes a rear window 104 , a left quarter window 106 , and a right quarter window 108 . The plurality of window attachments allows for selectively connecting the plurality of removable windows 102 to a foldable, stowable roof when it is desired to close off the vehicle interior from the outside environment.
Referring more particularly to FIG. 5 is a schematic incorporating a foldable, stowable roof 110 connected to the zipper less removable window assembly 100 without the use of zippers. The plurality of removable windows 102 are connectable to the foldable, stowable roof 110 and to the vehicle 11 using the plurality of window attachments having no zippers.
Referring more particularly to FIG. 6 , FIG. 6 is an enlarged sectional view taken along section A-A of FIG. 5 depicting the left quarter window 106 coupled to the foldable, stowable roof 110 . The left quarter window 106 is a zipper less removable window that connects to the vehicle and connects to the top deck 110 a curved area of the foldable, stowable roof 110 and connects to a deck side strip 116 . The left quarter window 106 has a quarter window glass 112 , most preferably, made of PVC. A quarter window carrier 114 is connected along the upper longitudinal edge of the quarter window glass 112 . Most preferably, a longitudinal recess or notch 113 is provided in the quarter window carrier 114 and the quarter window glass 112 is affixed to one or more abutting surfaces in the recess, e.g., using adhesive and/or a film adhesive, most preferably, sewing and/or combinations thereof. Preferably, the quarter window carrier 114 is formed of molded plastic, e.g., composite material, reinforced fibers, etc.
The quarter window carrier 114 has a first channel portion, shown generally at 115 , that is generally C-shaped. The first channel portion 115 is open on at least one end to slidably receive a bulb portion of a first ‘P’ welt retainer therein. A deck side strip 116 of fabric is connected to the top deck 110 a of the foldable, stowable roof 110 , most preferably, sewn to the top deck 110 a at one end, and is connected to the first ‘P’ welt retainer 118 toward the other end. The deck side strip 116 is wrapped around the first ‘P’ welt retainer 118 and connected thereto, e.g., using adhesive and/or, most preferably, sewing the first ‘P’ welt retainer 118 in a pocket formed by the deck side strip 116 . The first channel portion 115 of the quarter window carrier 114 is suitably sized to allow selective sliding of the elongated channel 115 along the length of the first ‘P’ welt retainer 118 and to retain the first ‘P’ welt retainer 118 longitudinally within the channel 115 while preventing undesirable lateral movement of the first ‘P’ welt retainer 118 out of the channel 115 , including, moving laterally out of the channel 115 .
The quarter window carrier 114 further has a second channel portion 119 that is generally U-shaped forming an elongated open channel that is generally angled downward and outward from the first channel portion 115 . The end of the top deck 110 a is connected to a top deck retainer 120 and binding top deck 122 portion. The top deck retainer 120 is selectively received within the second channel portion 119 . When it is desired to connect the quarter window glass 112 to the foldable, stowable roof 110 , the top deck 110 a is folded down over the outward side of the quarter window carrier 114 and the top deck retainer 120 is snapped into the second channel portion 119 . When it is desired to remove the quarter window glass 112 , an operator disengages the top deck retainer 120 from the second channel portion 119 . Preferably, the quarter top deck retainer 120 is formed of molded plastic, e.g., composite material, reinforced fibers, etc.
The right quarter window 108 and corresponding features are substantially mirror image to the left quarter window 106 and corresponding features.
Referring more particularly to FIG. 7 , FIG. 7 is an enlarged sectional view taken along section B-B of FIG. 5 depicting the rear window 104 coupled to the foldable, stowable roof 110 . The rear window 104 is a zipper less removable window that connects to the vehicle and connects to a rear valence top deck 132 curved rear area of the rear top deck 110 b of the foldable, stowable roof 110 . The rear window 104 also connects to a rear side strip 128 . The rear window 104 has a rear window glass 124 , most preferably, made of PVC. A rear window carrier 126 is connected along the upper longitudinal edge of the rear window glass 124 . Most preferably, a longitudinal recess or notch 125 is provided in the rear window carrier 126 and the rear window glass 124 is affixed to one or more abutting surfaces in the recess, e.g., using adhesive and/or a film adhesive.
The rear window carrier 126 has a third channel portion, shown generally at 127 , that is generally C-shaped. The third channel portion 127 is open on at least one end to slidably receive a bulb portion of a second ‘P’ welt retain therein. The rear side strip 128 of fabric is connected to the rear top deck 110 b of the foldable, stowable roof 110 , most preferably, sewn to the rear top deck 110 b at one end, and is connected to the second ‘P’ welt retainer 130 toward the other end. The rear side strip 128 is wrapped around the second ‘P’ welt retainer 130 and connected thereto, e.g., using adhesive and/or sewing the second ‘P’ welt retainer 130 in a pocket formed by the rear side strip 128 . The third channel portion 127 of the rear window carrier 126 is suitably sized to allow selective sliding of the elongated channel 127 along the length of the second ‘P’ welt retainer 130 and to retain the second ‘P’ welt 130 longitudinally within the channel 127 while preventing undesirable lateral movement of the second ‘P’ welt retainer 130 out of the channel 127 , including, moving laterally out of the channel 127 .
The end of the rear top deck 110 b is connected to a rear valance top deck 132 . Most preferably, an end of the rear valance top deck 132 and an end of the rear side strip 128 are sandwiched between an end of the rear top deck 110 b and a liner of the upper horizontal rear support bar of the vehicle, and connected together, e.g., sewn together.
The rear window carrier 126 further has a fourth channel portion 134 that is generally U-shaped forming an elongated open channel that is generally angled downward and outward from the third channel portion 127 . The lower end of the rear valance top deck 132 is connected to a rear top deck retainer 136 and rear binding top deck 138 portion. The rear top deck retainer 136 is selectively received within the fourth channel portion 134 . When it is desired to connect the rear window glass 104 to the foldable, stowable roof 110 , the rear valance top deck 132 is folded down over the rearward side of the rear window carrier 126 and the rear top deck retainer 136 is snapped into the fourth channel portion 124 . When it is desired to remove the rear window glass 104 , an operator disengages the rear top deck retainer 134 from the fourth channel portion 134 . Preferably, the rear window carrier 126 and rear binding top deck 138 is formed of molded plastic, e.g., composite material, reinforced fibers, etc.
Referring more particularly to FIG. 8 , FIG. 8 is an enlarged sectional view taken along section C-C of FIG. 5 depicting the left quarter rear window 106 coupled to the rear window 104 toward the left rear corner of the vehicle. A rear window side carrier 140 is connected along the vertical edge of the rear window glass 124 . Most preferably, an elongated recess or notch 141 is provided in the rear window side carrier 140 and the rear window glass 124 is affixed to one or more abutting surfaces in the recess, e.g., using adhesive and/or a film adhesive. The left quarter window 106 has a quarter window panel 144 of fabric connected to a rear quarter window retainer 142 . The rear quarter window retainer 142 is received in a fifth channel portion 143 formed in the rear window side carrier 140 that is generally U-shaped forming an elongated open channel to selectively receive and retain the elongated rear quarter window retainer 142 therein. Preferably, the rear window side carrier 140 and/or rear rear quarter window retainer 142 is formed of molded plastic, e.g., composite material, reinforced fibers, etc.
The right hand side of the rear window 104 coupled to the right quarter window 108 and all of the corresponding features are substantially mirror image to the left quarter window 106 and corresponding features coupled to the rear window 104 and corresponding features depicted in FIG. 8 .
FIG. 9 is a schematic for the vehicle of FIG. 5 identifying additional cross sections depicted in FIGS. 10-12 .
Referring more particularly to FIG. 10 , FIG. 10 is an enlarged sectional view taken along section D-D of FIG. 9 depicting the left quarter rear window 106 coupled to a removable door rail 148 . This provides the vertical connection along the front leading edge of the left quarter window 106 adjacent the rear edge of the door of the vehicle. The quarter window panel 144 of the left quarter window 106 is wrapped around and connected to a front quarter window retainer 146 , e.g., using adhesive and/or sewing the front quarter window retainer 146 in a pocket formed by the quarter window panel 144 leading edge. The front quarter window retainer 146 is L-shaped and elongated. A sixth channel portion 145 that is in the removable door rail 148 that is generally U-shaped forming an elongated open channel to selectively receive and retain one of the legs of the L-shaped front quarter window retainer 146 .
The right quarter window 108 and right removable door rail and corresponding features are substantially mirror image to the left quarter window 106 and removable door rail 147 and corresponding features depicted in FIG. 10 .
Referring more particularly to FIG. 11 , FIG. 11 is an enlarged sectional view taken along section E-E of FIG. 9 depicting the quarter window panel 144 of the left quarter window 106 connected, e.g., by adhesive and/or sewing a quarter window belt retainer 150 . The quarter window belt retainer 150 is located along the bottom of the left quarter window 106 for engaging between, and being retainable by, a belt rail 152 of the vehicle body and a quarter panel outer 154 of the vehicle body. The belt rail 152 is connected to the quarter panel outer 154 and a quarter panel inner 156 . The outward end of the belt rail 152 is curved to create a recess that is elongated for receiving and retaining the corresponding elongated quarter window belt retainer 150 . This provides the horizontal connection along the bottom edge of the left quarter window 106 to the vehicle.
The right quarter window 108 and corresponding features are substantially mirror image to the left quarter window 106 and corresponding features depicted in FIG. 11 .
Referring more particularly to FIG. 12 , FIG. 12 is an enlarged sectional view taken along section F-F of FIG. 9 depicting the rear window 104 for selectively coupling to a rear panel swing gate inner 158 . The rear window 104 comprises a rear window lower valence 162 connected to a third ‘P’ welt retainer 164 and a binding rear window 166 . The seventh channel portion is generally C-shaped and open on at least one end to slidably receive a bulb portion of the third ‘P’ welt retainer 164 therein. The rear window lower valence 162 of fabric is connected to the ‘P’ welt retainer 164 , e.g., using adhesive and/or sewn and/or sewing the third ‘P’ welt retainer 164 in a pocket formed by the fabric of the rear window lower valence 162 . The seventh channel portion 165 of the tailgate bar 167 is suitably sized to allow selective sliding and retention of the elongated third ‘P’ welt retainer 164 longitudinally within the channel 165 while preventing undesirable lateral movement of the third ‘P’ welt retainer 164 out of the channel 165 , including, moving laterally out of the channel 165 . This provides the horizontal connection along the bottom edge of the rear window 104 adjacent to the rear swing gate of the vehicle. A swing gate weather strip 168 , e.g., a bulb seal, is also provided to provide a sealing function between the tailgate bar 167 and a panel swing gate outer of the vehicle body 160 .
Referring generally to FIGS. 5-15 , in an embodiment of the present invention, the installation of the zipper less removable window assembly 10 will now be explained. When it is desired to close the removable rear window 104 a user aligns and slidably engages the rear window carrier 126 on the top of the window onto the rear side strip 128 where the second ‘P’ welt retainer 126 is located. The user slides the removable window 104 on the rear valance top deck 132 until the window is fully engaged across the length of the valance 132 . The user pre-engages the tail gate bar 167 onto the third ‘P’ welt retainer 164 at the bottom of the rear window 104 . The user slides the tail gate bar 167 on the front window ‘P’ welt retainer 164 until the tail gate bar 167 is fully engaged across the length of the third window ‘P’ welt retainer 164 . Then the user rolls the tail gate bar 167 into the tail gate bar clip 170 on the vehicle body. The user aligns the rear window corner retainer, e.g., binding rear window 166 with the tailgate clip 170 and snaps the rear window corner retainer into the tailgate clip. If the quarter windows do not require installation, the top deck 110 b / 132 can then be installed at the rear window 104 , as explained in greater detail below.
The installation of a quarter window will now be explained, e.g., left side quarter window 106 . When it is desired to close the removable left quarter window 106 (and/or right rear quarter window 108 ) a user aligns the quarter window carrier 114 on the top of the quarter window onto the deck side strip 116 at the upper rear corner. The user slides the quarter window carrier 114 along the deck side strip 116 until the left quarter window 106 is fully engaged along the length of the deck side strip 116 . The user pre-engages the front quarter window retainer 146 into the removable door rail 148 until the front quarter window retainer 146 is fully engaged into the removable door rail 148 . The user then tucks the upper quarter window flaps between the deck side strip 116 and the top deck 110 a at the front, e.g., toward direction of vehicle hood. The user aligns and engages the top deck retainer 120 to a quarter window upper front corner retainer. Then aligns and engages the top deck retainer 120 to the quarter window carrier 114 from the front corner across the top of the window. The top deck retainer 120 is engaged to the quarter window carrier 114 along the entire length. The user folds down the roof edge 110 .
The user then aligns and inserts the quarter window belt retainer into the vehicle body belt rail at the lower front corner, e.g., in the direction toward vehicle hood, until the quarter window belt retainer is fully inserted into the vehicle body belt rail 152 . The user aligns and engages the quarter window retainer 150 into the vehicle body belt rail 152 at a lower front corner of the quarter window 106 . The user inserts the quarter window retainer 150 until the quarter window retainer 150 is fully engaged into the vehicle body belt rail 152 .
The user aligns and engages the rear quarter window retainer 142 into the rear window side carrier 140 . The user aligns and engages the quarter rear belt rail retainer 150 into the vehicle body belt rail 152 at the lower rear corner of the vehicle.
The installation of the top deck at the rear window will now be explained. The user aligns and engages the rear top deck retainer 136 into the rear window carrier 126 at the upper corner, e.g., upper right corner on the rear of the vehicle. The user engages the rear top deck 136 retainer into the rear window carrier 126 along the entire length thereof.
In the fully installed position, the top deck is folded down over the top of the removable windows to help create a weather tight seal.
When it is desired to open at least one of the windows the steps described above can be facilitated in reverse to disconnect and remove the window(s) from the foldable, stowable roof.
It is understood that one or more removable windows can be selectively installed and removed. By way of non-limiting example, when it is desired by the user that the rear window be removed the quarter windows can selectively remain connected to the foldable, stowable roof.
The removable window having the zipper less attachment design of the present invention facilitates the opening and closing of the removable window. Accordingly, there is a significant benefit to the positioning of the attachment devices and along all the edges of the removable windows that are zipper less.
The description of the invention is merely exemplary in nature and, thus, variations that do not depart from the essence of the invention are intended to be within the scope of the invention. Such variations are not to be regarded as a departure from the spirit and scope of the invention. | A zipper less removable window system having removable windows for use with a foldable, stowable roof for a vehicle. A plurality of attachment devices of the zipper less removable window system connect the windows to the foldable, stowable roof and to the vehicle without the use of zippers. The operator zipper effort caused by traditional windows is thereby eliminated and misalignment issues present with traditional zippered windows is eliminated or reduced. The stress placed on the portions of the windows connectable to the foldable roof during installation and removal, including around curved portions of the removable window, is eliminated or reduced. | 1 |
BACKGROUND OF THE INVENTION
There is appreciable interest in production of food products having two, three, four or more ingredients; the food product usually includes a bottom food patty of a food material (e.g., chicken, turkey, pork, or veal) covered by a top food patty of the same or a different material. One or more additional ingredients, most often somewhat smaller than the top and bottom patties, are usually interposed between those patties. Typical products of this kind utilize chicken or turkey meat for the outer patties, with cheese, ham, stuffing, or condiments for the middle layer ingredients. A variety of other similar products are possible, including fish with crab or other stuffing as the middle ingredient, and beef or other meat with a variety of ingredients in the center of the food product. In any of these products, the top and bottom patties should be sealed together to afford a coherent plural-layer food product.
There are a number of high efficiency, high volume food patty molding machines that have been utilized for production of hamburger patties, other ground meat patties, chicken patties, fish patties, imitation steaks, and other molded food products. Four such machines that are commercially available are described in Richards et al. U.S. Pat. No. Re. 30,096, Sandberg et al. U.S. Pat. No. 4,054,967, LaMartino et al. U.S. Pat. No. 4,182,003 and Sandberg U.S. Pat. No. 4,768,260; these machines are available as the F26, F-19, F-12 and F-6 food patty molding machines, respectively, made and sold by Formax Inc. of Mokena, Ill., U S.A.
All of these high volume food patty molding machines are relatively flexible and each can produce a wide variety of food patties, depending upon the mold plate configuration and other mold station components in the machine. All can be used to produce molded food patties of whole muscle fiber, using the molding apparatus of Sandberg et al. U.S. Pat. No. 4,356,595 or Sandberg U.S. Pat. No. 4,697,308. However, these machines do not directly manufacture food products having two or more ingredients; additional equipment is required. This applies also to other food patty molding machines, particularly those that, like the machines identified above, use a reciprocating mold plate.
One known system for producing plural-layer food products uses two of the Formax F-19 patty molding machines of Sandberg U.S. Pat. No. 4,054,967, with one of those machines modified for a pass-through operation. That system deposits cheese, ham, condiments, or other ingredients onto a series of bottom food patties to form multi-layer food subassemblies on a continuously moving belt conveyor. A second, modified patty machine is used to deposit a top patty on each multi-layer subassembly to complete a food assembly, followed by a mechanism for "knitting" each assembly together to complete the food product. The system and its components are disclosed in a series of United States Patents of Oscar Mayer Foods Corporation; those U.S. patents are Jonovic et al. No. 4,684,040, Borsuk No. 4,709,449, Hartl et al. No. 4,714,014, and Mally et al. No. 4,716,821 and No. 4,832,970.
Maintaining registry between sequential plural layers of a food assembly, on a continuously moving conveyor, is quite difficult. The least variation in timing sequence for any part of the system is likely to produce an unacceptable end food product due to misalignment of layers of that product. A "knitting" mechanism that relies on multiple piercing operations to join two superimposed food patties, as in the previously discussed system, is likely to be unreliable whenever misalignment occurs; it is also difficult to attain reliable, consistent operation of equipment of this kind when working on the fly, with a continuously moving conveyor. Further, it may be noted that equipment on the Oscar Meyer line is all driven mechanically through a common drive shaft that limits flexibility of changes, additions, or deletions of equipment. Electronic sequencing is much preferable.
SUMMARY OF THE INVENTION
It is a principal object of the present invention, therefore, to provide a new and improved food product crimping apparatus for producing coherent, plural-layer food products from food assemblies of the kind comprising to and bottom food patties, usually with additional ingredients between them, that is capable of consistent, effective, efficient, high volume production.
Another object of the invention is to provide a new and improved food product crimping mechanism for a system that assembles and completes a plural-layer food product that can be utilized in conjunction with a wide variety of different food ingredients and that functions effectively with a cyclically, intermittently actuated conveyor.
A specific object of the invention is to provide a new and improved food product crimping mechanism that is relatively simple and inexpensive in construction yet efficient and long lasting in operation.
Accordingly, one aspect of the invention relates to a crimping mechanism for a crimping station producing a coherent plural-layer food product from a food assembly, the food assembly including at least a bottom food patty and a top food patty covering and supported by the bottom food patty, each patty formed of meat, poultry, or fish; the mechanism comprises intermittently operable food assembly positioning means for positioning a food assembly in a crimping position in the crimping station and maintaining the food assembly stationary in that crimping position for a predetermined crimping interval, confinement means for defining peripheral limits for a food product at the crimping position, the confinement means comprising a confinement tool movable between a rest position displaced from the crimping position and an actuated position encompassing the crimping position, crimping means for crimping peripheral portions of the top and bottom food patties of the food assembly together, at the crimping position, the crimping means comprising a crimping tool movable between a rest position displaced from the food assembly crimping position and an actuated position in which the crimping tool engages a peripheral portion of the top surface of the top food patty in pressure contact and presses that peripheral portion of the top food patty into the bottom food patty with no penetration of the crimping tool into the interior of either patty, and drive means for driving the confinement and crimping tools from their rest positions to their actuated positions and back to their rest positions during the crimping interval.
In another aspect the invention relates to a crimping mechanism for a crimping station producing a coherent plurallayer food product from a food assembly, the food assembly including at least a bottom food patty and a top food patty covering and supported by the bottom food patty, each formed of meat, poultry, or fish; the mechanism comprises a fixed base, located at the crimping station, intermittently operable food assembly positioning means for positioning a food assembly in a crimping position on the crimping station base and maintaining the food assembly stationary in that crimping position for a predetermined crimping interval, the food assembly positioning means comprising a cyclically driven belt-type conveyor extending across the base through the crimping station, a fixed frame member positioned above the crimping position in the crimping station, and a yoke, suspended from the frame member and movable toward and away from the crimping position. Confinement means are provided for defining peripheral limits for a food product at the crimping position, the confinement means comprising a confinement tool suspended from the yoke and movable toward and away from the base between a rest position displaced from the crimping position and an actuated position encompassing the crimping position; there are also crimping means for crimping peripheral portions of the top and bottom food patties of the food assembly together, at the crimping position, the crimping means comprising a crimping tool suspended from the yoke and movable toward and away from the base between a rest position displaced from the food assembly crimping position and an actuated position in which the crimping tool engages a peripheral portion of the top surface of the top food patty in pressure contact and presses that peripheral portion of the top food patty into the bottom food patty with no penetration of the crimping tool into the interior of either party. Drive means, mounted on the frame and connected to the yoke, are provided for driving the yoke reciprocally toward and away from the base during each crimping interval to drive the confinement and crimping tools from their rest positions to their actuated positions and back to their rest positions during the crimping interval.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic plan view of a food product system that includes a crimping station in which a crimping mechanism according to the present invention may be utilized;
FIG. 2 is a side elevation view of a preferred embodiment of the crimping mechanism of the present invention;
FIG. 3 is a sectional view taken approximately as indicated by line 3-3 in FIG. 2;
FIG. 4 is a sectional elevation view, on an enlarged scale, taken approximately as indicated by line 4--4 in FIG. 3;
FIG. 5 is a sectional view of one-half of the mechanism of FIG. 4 taken approximately as indicated by line 5--5 in FIG. 4;
FIG. 6 is a detail sectional view like FIG. 4 but at a later stage in the crimping cycle;
FIG. 7 is a sectional view corresponding to FIG. 4 but with the mechanism in the final stage of its cyclic operation; and
FIG. 8 is a plan view of a finished food product made in the mechanism of the invention, on the same scale as FIGS. 2 and 3.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
FIG. 1 affords a schematic plan view of a food production system 10 that includes a crimping station 20 in which a crimping mechanism constructed in accordance with the present invention may be incorporated. System 10 includes an intermittently, cyclically operated conveyor 11 that extends for the full length of the system. Conveyor 11 is preferably a belt-type conveyor. Starting at the top of FIG. 1, it is seen that conveyor 11 passes through the output end of a food patty molding machine 12. The food patty molding machine 12 is preferably one of the high volume, high capacity Formax machines identified more fully above. In each cycle of the patty molding machine 12 a food patty 13 is produced by the machine and is deposited upon conveyor 11. The timing of operation of conveyor belt 11 is coordinated with the cyclic operation of patty machine 12 so that the belt is stationary whenever a food patty is being produced; belt 11 advances a predetermined distance D during each molding interval when a new patty is being molded in machine 12.
After passing through the output portion of patty molding machine 12, belt conveyor 11 traverses one or more intermediate food layer stations 14. Only one such station 14 is shown in FIG. 1, but there could be two, three, or more intermediate stations. Station 14 applies a layer 15 of some food ingredient to the top of the bottom food patty 13. The food element 15 could be meat of some kind, fish or other seafood, cheese, butter, margarine, catsup, etc.
The mechanisms used in the intermediate layer station or stations 14 in system 10 may be of two general types. If the intermediate layer 15 is to be ham, sausage, or other meat product, or if it is to be a cheese, butter, or margarine station 14 may be a commercial slicer of the kind that ca be controlled so that it releases a slice cut from a sausage or ham segment or from a cheese at a predetermined controllable time interval. Such a slice of an intermediate layer or ingredient should be deposited centrally of the bottom patty 13, as indicated in FIG. 1. A suitable slicing machine for an operation of this kind is the Grote 522 slicer applicator of J. E. Grote Company, Inc., Blacklick, Columbus, Ohio, USA. Station 14 could also be another Formax patty former.
If the material from which the intermediate layer 15 is to be formed is of a flowable or particulate nature, application to the bottom patty 13 by a slicing mechanism is impractical. In situations of that kind, a condiment dispenser such as that described in Jonovic et al. U.S. Pat. No. 4,684,040 may be employed. For either type of machine, deposition of the intermediate layer 15 by station 14 should be timed to occur during those intervals when the intermittent conveyor belt 11 is stationary so that these intermediate layers can be accurately located on bottom patties 13.
After all intermediate layers 15 are in place on bottom patty 13, the subassemblies 13, 15 are advanced, on conveyor belt 11, into the output or discharge portion of a second food patty molding machine 16. Machine 16 is preferably of the identical type with machine 12 and produces a top patty 17 of approximately the same size and configuration. This completes a food assembly 18 that includes the bottom patty 13, the top patty 17, and any intermediate layers or patties 15.
In system 10 of FIG. 1, the next station 20 is a crimping station, constructed in accordance with the present invention, that operates to produce a coherent plural-layer food product 30 from each stack or food assembly 18 entering mechanism 20 on the intermittent conveyor 11. The manner in which the completed coherent food products 30 are transferred away from the system is of no interest in connection with the present invention and hence has not been shown in FIG. 1. A drive 19 for conveyor 11 is illustrated in FIG. 1. The conveyor drive 19 should actuate the conveyor belt to advance it through the distance D each time one of the stations 12, 14 and 16 functions to deposit a new food patty or condiment component on the conveyor belt. Furthermore, the timing of all of the machines in system 10, comprising patty molding machines 12 and 16, intermediate layer machine or machines 14, and crimping mechanism 20, as well as their spacing along conveyor 11, should be coordinated with operation of conveyor drive 19.
As shown in FIGS. 2 and 3, the crimping mechanism incorporated in station 20 comprises a base 21 upon which a base plate 22 is mounted; there are two conveyor guides 23 at opposite sides of base plate 22. Four vertical supports 24 are mounted on and extend upwardly from the base 21 of station 20 and support a relatively heavy plate or frame member 25. Thus, members 24 and 25, together with base 21 afford a rigid, stationary frame for the operating mechanism of crimping station 20.
A power cylinder 26 is mounted on frame member 25 and is secured thereto by a large nut 27 (FIG. 2). Power cylinder 26 has a piston rod 28 that projects downwardly, below frame member 25 and nut 27. The lower end 28A of piston rod 28 is threaded into the center of a yoke 31; a nut 29 is used to adjust the height of yoke 31. Yoke 31 is shown as having a circular configuration. Furthermore, all of the other tooling in crimping station 20 is also shown as being essentially circular in shape, corresponding to an anticipated circular configuration for the top and bottom patties 13 and 17 in the food product 30 produced by station 20. It should be understood that this circular configuration is the preferred one because it minimizes the possibility of orientation error. On the other hand, other shapes (square, hexagonal, octagonal, etc.) may be utilized.
Crimping mechanism 20, FIGS. 2 and 3, includes three yoke guide rods 32 that are affixed to yoke 31 and that extend upwardly from the yoke through individual yoke guide sleeves 33 mounted in the top plate, frame member 25. Rods 32 and sleeves 33 control and guide vertical movements of yoke 31, actuated by power cylinder 26, in the operation of mechanism 20.
The operating mechanism of crimping station 20, FIGS. 2 and 3, further includes a cylindrical confinement tool 34 that is positioned below and suspended from yoke 31. A series of confinement guide rods 35 are fixed to the top of the cylindrical confinement tool 34. The upper portion of each guide rod 35 extends through an aperture in yoke 31, as better shown in FIGS. 4 and 7, with the head 36 of each rod engaging the top of the yoke. There is a spring 37 disposed in encompassing relation to each guide rod 35, between yoke 31 and confinement tool 34.
FIGS. 4-7 provide more detailed information about the operating mechanism of crimping station 20 (FIGS. 2 and 3) and illustrate components not thus far mentioned that are an integral part of the crimping mechanism. Thus, as shown in FIGS. 4 and 7, each yoke guide rod 32 may be secured to yoke 31 by an appropriate bolt or other fastener 38. The mounting of power cylinder 26 in the plate comprising frame member 25 may comprise a collar 39 that fits closely into an aperture 41 in plate 25. A threaded extension 42 of power cylinder 26 is engaged by nut 27 to complete the mounting for the power cylinder on frame member 25.
Another major component of the crimping mechanism in station 20 is a crimping tool 43, FIGS. 4-7. Crimping tool 43 is of generally inverted cup-shaped configuration, preferably having a downwardly facing serrated rim 44. The lower surface of crimping tool 43 is of steppe configuration, providing an annular recess 45 that extends inwardly from the serrated rim 44 and that leads to a central, deeper recess 46. Crimping tool 43 is suspended from yoke 31 by a plurality of suspension bolts 47 whose heads 48 engage the top of yoke 31 as shown in FIGS. 2-4 and 7. A spacer sleeve 49 encompasses each suspension bolt 47 (FIGS. 4 & 7) to establish the spacing between crimping tool 43 and yoke 31. Each bolt 47 is threaded into a tapped hole in crimping tool 43.
A disk-shaped tamping tool 51 is disposed within the central recess 46 in crimping tool 43. A mounting screw 52 having a head that is flush with the lower surface of the tamping tool extends upwardly through the tamping tool and is threaded into a tapped opening in the bottom of a vertically extending guide rod 53. A guide collar 54 is affixed to the upper portion of guide rod 53, which projects a substantial distance above the top of crimping tool 43. There is a guide bushing 55 in crimping tool 43, through which guide rod 53 extends. See FIGS. 4, 6 & 7. A coil spring 56 is disposed in encompassing relation to the guide rod 53. The bottom of coil spring 56 engages the top of guide collar 54; the upper end of spring 56 is positioned within a recess 57 in the bottom of yoke 31.
There are three small spacer rods 58 in mechanism 20, each threaded into a tapped opening in crimping tool 43 as shown in FIGS. 4, 6 & 7. Each spacer rod 58 projects downwardly into the central recess 46 in the crimping tool to establish an upper limit for movement of tamping tool 51 by engaging the top of the tamping tool. Each spacer rod 58 is held in position by a nut 59. The equiangular distribution of spacer rods 58 about the central axis 60 of the crimping mechanism in station 20 can best be seen in FIG. 3.
There are also six aeration pins 61 in crimping mechanism 20. The location of the aeration pins 61 is best shown in FIG. 3; the pin construction is best shown in FIGS. 4-7. Each pin 61 extends down into a vertical axial opening in tamping tool 51, as shown in FIGS. 4, 6 & 7. The top portion of each pin 61 is a threaded rod 62 that is threaded into a tapped opening in crimping tool 43 and held in place, vertically, by a nut 63.
In considering the operation of the crimping mechanism 20 of FIG. 2-7, the starting point is the operating condition for the mechanism and the rest positions for the various tools of that mechanism, as shown in FIGS. 2-5. As will be apparent from the foregoing description, yoke 31 is suspended from member 25 of the frame at crimping station 20, being suspended from the lower, threaded end 28A of the piston rod 28 of power cylinder 26, which in turn is affixed to frame member 25. The elevated, rest position for yoke 31 is shown in FIGS. 2-4. Yoke 31 is movable vertically, with its movement guided by rods 32, in response to operation of power cylinder 26.
Each of the principal tools in crimping mechanism 20 has an elevated rest position (FIGS. 2-5) and an actuated position. The elevated rest position for crimping tool 34 is shown in FIGS. 2-5; for this position, the lower rim 34A of the crimping tool is displaced a substantial distance above the top surface of conveyor belt 11. The actuated position for confinement tool 34 is illustrated in FIGS. 6 and 7. For tamping tool 51, the elevated rest position is also shown in FIG. 4. The actuated position for tamping tool 51, which is a part of the air release apparatus of crimping station 20, is shown in FIG. 6; the tamping tool also occupies the same actuated position in FIG. 7.
Crimping tool 43, on the other hand, starting from its elevated rest position in FIG. 4, has not completed its downward movement by the time the mechanism reaches the stage shown in FIG. 6. Thus, in FIG. 6 crimping tool 43 is at an intermediate location between its rest position (FIG. 4) and its actuated position, shown in FIG. 7. This applies also to the pins 61, which are affixed to crimping tool 43 and move conjointly with it.
Starting with FIGS. 4 and 5, it is seen that the food assembly 18, including its bottom patty 13 and top patty 17, is positioned in centered relation within crimping mechanism 20 immediately below the central opening in the cylindrical crimping tool 43. See also FIG. 1. When food assembly 18 reaches that crimping position, movement of belt conveyor 11 is interrupted. Belt 11 then maintains food assembly 18 in the crimping position shown in FIGS. 4-7 for a predetermined crimping interval, during which mechanism 20 operates to crimp the lower and upper patties 13 and 17 together to complete a coherent plural-layer food product 30 (FIG. 8).
With food assembly 18 in the crimping position in mechanism 20, power cylinder 26 is actuated to drive piston rod 28, 28A downwardly, moving yoke 31 downwardly away from the fixed frame member 25. In the course of this movement, the confinement tool 34 that is suspended from yoke 31 on rod 35 is shifted downwardly so that its lower rim 34A engages the top surface of conveyor belt 11. This does no harm to the conveyor, because the conveyor belt is not moving. The actuated position for confinement tool 34 is shown by phantom outline 34B in FIG. 4 and is shown in solid lines in FIGS. and 7. In its actuated position, FIGS. 6 and 7, confinement tool 34 encompasses the crimping position occupied by food assembly 18 and establishes limits beyond which the food assembly cannot expand when tamped and crimped to complete the food product 30 as described below.
After confinement tool 34 reaches its actuated position, continued downward movement of piston rod 28 and the resulting downward movement of yoke 31 cause crimping tool 43 and the air release means associated with that crimping tool to move downwardly relative to confinement tool 34, compressing springs 37 on guide rods 35. The next stage in the overall operation of mechanism 20 is that shown in FIG. 6, in which tamping tool 51 engages the upper surface of the top food patty 17 of assembly 18. From the point shown in FIG. 6, only a quite limited downward movement of tamping tool 51 remains possible ,and this limited movement squeezes air out of food assembly 18. That is, tamping tool 51 is a part of an air release means, incorporated in mechanism 20, for reducing entrapped air between the top and bottom food patties 17 and 13 in the finished food product 30 (FIG. 8) to be made from assembly 18.
Power cylinder 26 remains actuated and continues to drive completing the yoke 31 downwardly to the level illustrated in FIG. 7. This drives crimping tool 43 all the way to its actuated position, in which the rim 44 of the crimping tool presses a peripheral portion of the top food patty 17 down into the corresponding portion of the bottom food patty 13, sealing the top and bottom food patties 17 and 13 together. With the illustrated food assembly 18, of course, this seals the intermediate ham and cheese layers 15A and 15B into the interior of the completed food product 30. All layers may be spread out in the tamping/crimping process. The overall configuration of the completed food product 30 is shown in FIG. 8, with a serrated edge 66. For some food products it is not necessary to have a serrated rim 44 on crimping tool 43; a smooth crimp rim on the final food product may be adequate. In the final movement of crimping tool 43 to the actuated position of FIG. 7, pins 61 are also driven downwardly through the central portion of the food assembly. Preferably, the pin lengths are such that the bottom end of each pin is interrupted in its downward movement at a point approximately coincident with the upper surface of the bottom patty 13; see FIG. 7. However, this relationship is not critical. The purpose of pins 61 is to release additional air from within the finished product 30 (FIG. 8) through holes 67 formed by pins 61.
When the coherent, sealed food product has been completed, at the stage shown in FIG. 7, power cylinder 26 is reversed in its operation to pull piston rod 28 and yoke 31 back to their original positions as shown in FIG. 4. As yoke 31 begins its upward movement from the position of FIG. 7 to that shown in FIG. 4, springs 37 and 56 operate to restore the original spacings between the components of mechanism 20 so that the mechanism is restored to the rest condition shown in FIG. 4. At this point, which marks the completion of the required crimping interval, conveyor belt 11 is again stepped to advance the belt through system 10 (FIG. 1) by the distance D and the crimping cycle is repeated. | A cyclic crimping mechanism for producing coherent plural-layer food products from food assemblies, each food assembly including a bottom patty covered by a top patty (other patties, food slices, or condiments are usually positioned between the top and bottom patties), uses a cyclically, intermittently actuated conveyor to locate each food assembly at a crimping position for a predetermined crimping interval; in sequence, a confinement tool is moved down to an actuated position to define peripheral limits for the food product, a tamping tool is pressed down onto the food assembly to reduce air entrapment, and a crimping tool presses the periphery of the top patty into the bottom patty to seal them together in a coherent food product, after which these tools are all elevated to rest positions clear of the crimping position and the conveyor operates to move the finished food product away and position a new food assembly at the crimping position to start the crimping cycle anew. The crimping tool may include pins that pierce the central part of the food assembly for additional air release. | 0 |
BACKGROUND OF THE DISCLOSURE
[0001] The present disclosure relates to warning lights, and more particularly to warning light assemblies for use with a motor vehicle.
[0002] Warning lights in the form of light bars mounted on emergency vehicles are well known in the art. Warning lights are utilized on many different types of vehicles to give visual indications of their presence during emergencies. Warning lights typically comprise an elongated base, a plurality of electronic components, and at least one lens portion. The elongated base may be provided in the form of an extrusion.
[0003] Warning lights are traditionally required by state and federal safety regulations to produce very bright light with specific color and emission patterns. As a result, the electronic components and warning light assemblies give off a great deal of heat. Warning light assemblies, particularly those using light emitting diodes (LEDs), are able to put out less light and can be damaged when operated at higher temperatures.
[0004] When used on emergency motor vehicles, warning lights are exposed to a wide range of environmental conditions. As dirt, water, and salt may corrode metal parts, fog the lenses, and destroy electronic components, warning lights must provide a weather-resistant barrier against the elements.
[0005] The modern trend is toward compact, low profile, self-contained warning light assemblies. Given the well-known issues of heat generation and protection from the elements, modern light bars must simultaneously provide a strong weather-resistant seal while providing an efficient pathway for heat generated within. U.S. Pat. Nos. 7,611,270 and 6,863424, assigned to the assignee of the present disclosure are illustrative of warning light assemblies utilizing two different configurations to seal the warning light against the elements and provide an efficient path to direct heat away from the electronic components.
SUMMARY
[0006] According to aspects of the disclosure, a warning light for attachment to a vehicle comprises a thermally conductive longitudinally extending base, a plurality of mounting assemblies, a plurality of warning light assemblies, and at least one light-transmissive dome secured to the base.
[0007] The base has a pair of generally parallel longitudinal edges configured to engage the base and defines a pair of longitudinally extending light head shoe retention pockets adjacent to and oriented away from the edges. A pair of longitudinally extending ribs are spaced laterally inwardly of the retention pockets and project generally perpendicular from the base. The ribs terminate in a ridge and have a light head shoe retention lip projecting laterally toward the retention pocket at a point intermediate the base and the ridge. The light head shoe retention lip defines a retention channel oriented towards the base.
[0008] The plurality of mounting light assemblies generally comprise a plurality of brackets and a corresponding plurality of light head retention shoes. Each of the brackets are constructed of thermally conductive material, and have a generally planar bracket first portion in contact with the base and a generally planar bracket second portion to support a light generator. The bracket first portion is oriented generally perpendicular to the bracket second portion. A plurality of LEDs are mounted in thermally conductive contact to the bracket second portion.
[0009] Each of the plurality of light head retention shoes has a sole having a leading edge and toes configured to engage the retention pocket of the base and to maintain the bracket first portion in thermally conductive contact with the base. A rib engaging portion is located laterally opposite the foot. The rib engaging portion has a plurality of fingers configured to engage the distal ridge and a flexible retention member configured to reversibly engage the retention channel. A brace having a web and opposed sidewalls extends angularly between the rib engaging portion and the sole. The sidewalls project generally perpendicularly from the web and form a rigid structure.
[0010] In accordance with a further aspect of the disclosure, the light-transmissive dome has a generally planar main body portion oriented generally parallel to the base and longitudinally opposed inner and outer ends. Longitudinally extending sidewalls are contiguous with and extend generally perpendicularly from the main body portion, and terminate in a bottom edge. The main body portion defines a shallow longitudinally extending dome channel sized to receive a longitudinally extending panel. The outer end has an end wall contiguous with and extending generally perpendicularly from the main body portion, and terminates in a bottom edge. The end wall is oriented contiguous with and generally transverse to the sidewalls. The parallel longitudinal edges define a longitudinally extending dome-securing channel configured to receive the bottom edge of the longitudinally extending sidewalls and define an interior cavity.
[0011] In accordance with a further aspect of the disclosure, the longitudinally extending ribs define a center channel sized to receive at least one PC board and a plurality of arch-shaped bridges. Each of the bridges has laterally opposed pairs of feet. A snap fit connector extends away from the bridge. The snap fit connector is configured to reversibly mate with notch defined on at least one of the ribs.
[0012] The bridge also has a PC board retention member which comprises a cantilevered snap fit connector. A PC board retention snap works cooperatively with a nub. The nub is configured to engage one of a plurality of locator holes defined on longitudinally opposed ends of the control PC board to secure the control PC board within the center channel.
[0013] The configuration of the warning light in the current disclosure reduces the part count and the number of tools required for assembly. Additionally, the modular design of the disclosure gives greater flexibility in the lay out of the warning light. The light heads may be located anywhere along the base, since there are no restrictions or fixed points where the hardware must be located to secure the light heads to the base.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] Aspects of the preferred embodiment will be described in reference to the Drawings, where like numerals reflect like elements:
[0015] FIG. 1 is a side view of one embodiment of the warning light of the present disclosure, with particular emphasis on a light head shoe, a bracket, and the rib and retention pocket of the base, all other components of the warning light are omitted for clarity;
[0016] FIG. 2 is a perspective cross-sectional view of one embodiment of the warning light of the disclosure, the cross section is depicted as intersecting the warning light intermediate sidewalls of one of the light head shoes;
[0017] FIG. 3 is a perspective view of the embodiment of the light head retention shoe and the bracket of FIG. 2 ;
[0018] FIG. 4 shows a perspective view of one embodiment of the warning light; the generally concave light transmissive dome for a portion of the warning light is omitted for clarity, a mount to attach the warning light to a vehicle is also depicted;
[0019] FIG. 5 shows a rear view of the embodiment of the bracket depicted in FIG. 2 ;
[0020] FIG. 6 shows an embodiment of the bracket configured for use with shoes disposed at longitudinal ends of the base;
[0021] FIG. 7 is a perspective view of one embodiment of the base having a bridge received in a center channel defined intermediate the ribs, the warning light mount of FIG. 4 is also included;
[0022] FIG. 8 shows a perspective view of the underside of the light transmissive dome;
[0023] FIG. 9 shows a top plan view of the longitudinal ends of the base and the embodiment of the bracket depicted in FIG. 6 interfacing with a longitudinal end of the base, all other components of the warning light are omitted for clarity;
[0024] FIG. 10 is a perspective view of the bridge depicted in FIG. 7 , all other components of the warning light are omitted for clarity;
[0025] FIG. 11 shows a side view, partly in perspective, of one embodiment of an emergency warning light, the warning light mount depicted in FIG. 4 is also included;
[0026] FIG. 12 shows a cross-sectional view of the emergency warning light of FIG. 11 , the plurality of LED assemblies, mounting and control circuits have been omitted for clarity;
[0027] FIG. 13 is a cross-sectional view of one embodiment of the warning light with particular emphasis on the interface between one of the sidewalls and the longitudinal edge of the base, the plurality of LED assemblies, mounting and control circuits have been omitted for clarity; and
[0028] FIG. 14 is a cross-sectional view of one embodiment of the warning light with particular emphasis on the interface between the inner edge of the dome, the dome coupler and the wipe seal, the plurality of LED assemblies, mounting and control circuits have been omitted for clarity.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0029] Embodiments of a warning light will now be described with reference to the Figures, wherein like numerals represent like parts throughout the FIGS. 1-8 . FIGS. 1 , 2 and 7 depict a warning light 100 for attachment to a vehicle comprises a longitudinally extending base 102 constructed from a thermally conductive material. In one embodiment, the base 102 is an aluminum extrusion.
[0030] The base 102 has a generally parallel pair of longitudinal edges 104 . Laterally inwardly of the longitudinal edges 104 , the base 102 defines a pair of light head retention pockets 106 . The pocket 106 is defined along substantially the entire length of the base 102 . The pockets 106 are defined on the base 102 such that the pocket opens generally away from the nearest longitudinal edge 104 toward the center of the base.
[0031] As seen in FIGS. 1 , 2 , 4 and 7 , a pair of ribs 108 extends substantially the entire length of the base 102 . The ribs 108 project from the base 102 intermediate the retention pockets 106 , and run longitudinally parallel with the retention pockets 106 and the edges 104 . The ribs 108 are equidistantly spaced from a central medial axis A-A ( FIG. 4 ) and prevent warping under the aerodynamic forces that may act on the base by providing structural support.
[0032] As best seen in FIGS. 1 , 2 and 7 , the ribs 108 project perpendicularly from the base 102 and terminate in a distal ridge 110 . In one embodiment, the ridge 110 is rounded and runs the length of the base 102 . A retention lip 112 projects laterally toward the retention pocket 106 . The retention lip 112 projects from the rib 108 at a point intermediate the base 102 and the ridge 110 .
[0033] The retention lip 112 has a ramped cross section having an increasing width, as best seen in the embodiment depicted in FIGS. 1 and 2 . The retention lip 112 defines a retention channel 114 oriented toward the base 102 and having a generally concave cross-section. The retention lip 112 projects along the entire length of the rib 108 .
[0034] As best seen in FIGS. 1 , 2 , 3 and 5 , the warning light also has a plurality of brackets 116 constructed from a thermally conductive material. Given its thermally conductive characteristics, superior workability and cost, in a preferred embodiment, the brackets 116 are constructed from sheets of aluminum. The brackets 116 have generally planar first and second portions 118 and 120 , respectively. The bracket 116 is configured such that the bracket second portion 120 is oriented generally perpendicular to the bracket first portion 118
[0035] As depicted in FIG. 2 , a plurality of light emitting diodes (LEDs) 121 are mounted in thermally conductive contact to the bracket second portion 120 . In the embodiment of the warning light 100 depicted in FIG. 2 , the LEDs 121 are mounted to a PC board 123 and are operatively mounted within a reflector 125 . Though a PC board 123 and reflector 125 are utilized in the embodiment shown, any of a multitude of configurations to mount the LEDs 121 to the bracket 116 may be utilized without departing from the scope of the disclosure.
[0036] In one embodiment depicted in FIGS. 1 , 2 and 5 , the bracket first portion 118 has a stepped configuration. In this embodiment, a ledge 122 extends perpendicularly between first and second generally planar steps 124 and 126 , respectively. The ledge 122 and first and second steps 124 and 126 define a plurality of engagement slots 128 .
[0037] In one embodiment best seen in FIG. 5 , the first step 124 has a plurality of laterally projecting retention pocket engaging extensions 130 . The pocket engaging extensions 130 are constructed to engage the retention pocket 106 on the base 102 to ensure the brackets are secured against the base 102 in thermally conductive contact with the base 102 .
[0038] A plurality of light head retention shoes 132 correspond in number with the brackets 116 , and are best shown in FIGS. 1-4 . The shoes 132 are configured to engage the brackets 116 to provide a secure connection between the brackets 116 and the base 102 . In one embodiment, the shoes 132 are molded plastic components.
[0039] Each shoe 132 has a sole 134 a leading edge 138 , and toes 140 configured to engage the bracket first portion 118 . The sole 134 is oriented generally parallel to the base 102 , and has a leading edge 138 . In one embodiment ( FIGS. 2 and 3 ), the sole 134 is generally planar. The planar configuration of the sole 134 is complementary to the bracket first portion 118 having a stepped configuration. The sole 134 is configured to maintain the first step 124 flat against the base 102 . A plurality of toes 140 project from the sole 134 along the leading edge 138 . The toes 140 are projections configured to engage the pocket 106 of the base 102 . The plurality of engagement slots 128 defined by the ledge and first and second steps are sized to receive the toes 140 adjacent the extensions 130 .
[0040] As seen in FIGS. 2 and 3 , when the embodiment of the light head shoe 132 is correctly installed, the leading edge 138 abuts the bracket ledge 122 . The toes 140 of the shoe 132 project through the slots and engage the retention pocket 106 , while the leading edge 138 simultaneously provides a retentive force on the bracket first portion in a direction laterally toward the edge 104 of the base 102 . In the embodiment of the bracket 116 having laterally projecting pocket engaging extensions, the retentive force provided by the leading edge 138 additionally causes the pocket engaging extensions 130 to engage the retention pocket 106 . The leading edge thus acts in concert with the pocket engaging extensions 130 to provide an additional retentive force on the bracket 116 directed towards the base 102 .
[0041] In an embodiment of the light head shoe 132 depicted in FIGS. 1-4 , the light head shoes 132 also have a rib engaging portion 142 . Specifically referring to FIGS. 1 and 2 , the rib engaging portion 142 is configured laterally opposite the leading edge 138 , and comprises a plurality of engagement fingers 144 and a flexible retention member 146 . The engagement fingers 144 are designed to engage the ridge 110 of the ribs 108 . The engagement fingers 144 are configured to complement the shape of ridge 110 . For example, in the embodiment where the ridge 110 is rounded, the fingers have an arch-shaped cross section.
[0042] In the embodiment shown in FIG. 3 , the flexible retention member 146 is disposed between the engagement fingers 144 . The flexible retention member 146 is a cantilevered snap fit connector. While the resilient retention member 146 comprises a u-shaped cantilevered snap fit connector in the embodiment depicted in FIGS. 2 and 3 , other shaped configurations of cantilevered snap fit connectors may be employed without departing form the scope of the disclosure.
[0043] Referring specifically to FIGS. 1 , 2 and 3 , a brace 148 extends angularly between the sole 134 and the rib engaging portion 142 . The brace 148 has a web 150 , and a pair of opposed sidewalls 152 projecting generally perpendicularly from the web 150 forming a rigid structure. In one embodiment, the sidewalls 152 are oriented parallel to one another, and extend angularly between the sole 134 and the rib engaging portion 142 . As shown in FIG. 1 , the engagement fingers 144 extend from the sidewalls 152 .
[0044] In addition to holding the brackets 116 against the base 102 , the shoes 132 also frictionally secure the brackets 116 longitudinally along the base 102 adjacent the edge 104 . To install the shoe 132 and bracket 116 , the bracket first portion 118 is first laid flat against the base 102 adjacent the edge 104 . The pocket engaging extensions 130 are installed in the pocket 106 and the toes 140 are inserted into the engagement slots 128 adjacent the pocket engaging extensions 130 . The toes 140 are inserted into the pocket 106 , and the leading edge 138 exerts a force on the bracket laterally toward the edge 104 . The shoe 132 is pivoted downwardly so that the engagement fingers 144 engage the ridge 110 , and the flexible retention member 146 snaps into the retention channel 114 .
[0045] A multitude of lighting configurations are possible as a result of the structural configuration of the base 102 , the brackets 116 and the shoes 132 . Since there are no fixed areas where hardware must be located to secure light heads to the base, different light patterns may be achieved using the same mounting apparatus and without perforating the base 102 for multiple mounting hardware configurations. Different LEDs and optical elements may also be used to change the pattern of the light emitted without changing the brackets 116 or the shoes 132 .
[0046] FIGS. 4 , 6 and 9 show one embodiment of the bracket 116 specifically configured for use with light head shoes 132 disposed at longitudinal ends 153 of the base 102 . In this embodiment, the bracket 116 includes a third bracket portion 154 . The third bracket portion 154 is configured adjacent to and extends angularly away from the second bracket portion 120 , and oriented generally transverse to the bracket first portion 118 .
[0047] As shown in FIGS. 4 , 7 and 10 , the warning light 100 includes an arch-shaped bridge 156 . The bridge 156 extends between laterally opposed pairs of feet 158 . As best seen in FIG. 7 , in this embodiment the ribs 108 define a center channel 160 laterally opposite the light head shoe retention lips 112 . The center channel 160 receives at least one PC board 162 configured to selectively energize the LEDs (not shown).
[0048] Referring specifically to FIG. 10 , the bridge 156 has at least one snap fit connector 164 that extends axially away from the feet 158 . The snap fit connector 164 includes a laterally projecting protrusion 166 at each lateral end. As seen in FIGS. 4 and 7 , the protrusion 166 reversibly mates with a longitudinal fixation notch 168 defined on the ribs 108 .
[0049] The bridge 156 has a PC board retention member 170 including a cantilevered snap 172 which cooperates with a nub 174 to secure the PC board 162 within the center channel 160 . A plurality of locator holes 176 are defined on longitudinally opposed ends of the PC board 162 and sized to receive the nub 174 . The cantilevered snap 172 has a barb 178 , which prevents the locator holes 176 from dislodging from the nub 174 to retain the PC board 162 in a fixed location relative to the base 102 .
[0050] In one embodiment depicted in FIG. 10 , the feet 158 have laterally extending tabs 180 extending inwardly and outwardly. In this embodiment, the base 102 defines a pair of tracks 181 defined intermediate and running longitudinally parallel with the ribs 108 ( FIG. 7 ). The tracks 181 are configured to receive the laterally extending tabs 180 and secure the bridge 156 to the base 102 .
[0051] Referring to FIGS. 8 , and 11 - 14 , a generally light transmissive dome 182 is operatively connectable to the base 102 to define an enclosure. In one embodiment, the dome 182 has a main body portion 184 oriented generally parallel to the base 102 . The main body portion 184 defines a longitudinally extending dome channel 186 which extends between longitudinally opposed outer and inner ends 188 and 190 , respectively ( FIG. 11 ) on top of the warning light. In one embodiment, the dome channel 186 spans a majority of the lateral width of the dome 182 .
[0052] A panel 187 is received in the dome channel 186 . In one embodiment, the panel 187 is opaque, and obscures views of the internal components of the warning light. The panel 187 may also act as a sunshade, to prevent radiant energy from the sun's rays from heating up the interior of the light bar. As disclosed, the panel 187 is secured to the dome 182 by a plurality of fasteners 189 extending through the dome to engage receptacles on the bridges 191 ( FIG. 10 ). The panel 187 is extruded aluminum, though a plurality of other suitable materials may be used.
[0053] As best seen in FIGS. 11-13 , sidewalls 192 extend the length of the dome 182 , between the outer and inner ends of the dome 188 and 190 . The sidewalls 192 are contiguous with and extend generally perpendicular from the main body 184 , and terminate in a bottom edge 194 . As shown in FIGS. 8 , 12 and 13 , a bottom wall portion 196 projects generally perpendicularly inwardly from the sidewall 192 . In this embodiment, the bottom edge 194 is defined at the laterally inward most portion of the bottom wall 196 .
[0054] In an embodiment of the dome 182 depicted in FIGS. 8 and 11 , an end wall 198 located at the first terminal end 188 projects generally perpendicularly away from the main body portion 184 . The end wall 198 terminates in a bottom edge 200 which includes fastener apertures 208 . The end wall 198 is oriented generally transverse to the sidewalls 192 , and the end wall 198 and end wall bottom edge 200 are contiguous with the sidewalls 192 and sidewall bottom edge 196 , respectively.
[0055] The dome 182 is configured to reversibly mate with the longitudinally extending base 102 . In one embodiment best seen in FIGS. 12 and 13 , the longitudinal edge 104 of the base 102 defines a longitudinally extending dome-securing channel 204 , which runs the length of the base 102 . The sidewall bottom edges 194 are configured such that the dome-securing channel 204 receives the sidewall bottom edges 194 , securing the dome 182 to the base 102 . To secure the dome 182 to the base 102 , the sidewall bottom edges 194 at the inner end 190 are first inserted into the dome-securing channel 204 . Once the sidewall bottom edges 194 are introduced into the dome-securing channel 204 , the dome 182 slides longitudinally on the base 102 until the end wall bottom edge 200 abuts one of the longitudinal ends 153 of the base 102 .
[0056] In one embodiment shown in FIG. 8 , the sidewall bottom edge 194 has an interrupted rail 202 , which projects away from the sidewall bottom edge 194 . The rail 202 is sized to fit in the dome-securing channel 204 and ensures a secure connection between the dome 182 and the base 102 along the edges 104 . The rail 202 is configured to reduce friction between the rail 202 and the dome-securing channel 204 during installation of the dome 182 .
[0057] As shown in FIG. 13 , a lip 206 which projects downwardly away from the sidewall bottom edge 194 adjacent the rail 202 may also be provided. The lip 206 further ensures that the elements do not penetrate the interior of the warning light 100 . The lip 206 extends along the front and rear edges of the light bar 100 to direct moisture away from the channel 204 .
[0058] As best seen in FIGS. 8 and 11 , a plurality of fasteners 205 are utilized to ensure a secure connection between the dome 182 and the base 102 . As best seen in FIG. 8 , the end wall bottom edge 200 defines a plurality of fastener holes 208 . The fastener holes 208 are defined on the end wall bottom edge 200 such that they align with fastener receptacles 210 defined on the base 102 ( FIG. 12 ).
[0059] As shown in FIGS. 4 , 7 and 10 , the bridges 156 are configured to cooperate with fasteners 189 to secure the dome 182 and the panel 187 to the base. As best seen in FIG. 10 , a plurality of fastener receptacles 191 project axially from the feet 158 of the arch shaped bridge 156 . The receptacles 191 are sized to receive the fasteners 189 and hold the main body portion 184 and the panel 187 against the base 102 . The receptacles 191 and fasteners 189 work in concert with the dome 182 , panel 187 , and base 102 to maintain the original shape of the warning light 100 , despite aerodynamic forces that act on warning lights when vehicles travel at high speeds.
[0060] As shown in FIGS. 11 and 14 , the warning light 100 has two generally light transmissive domes 182 . The domes 182 are installed on the base 102 such that the inner longitudinal ends 190 of the dome are oriented toward one another. The inner longitudinal ends 190 of the domes 182 are received in a dome coupler 212 when the longitudinal fasteners are secured to the dome securing pockets 210 .
[0061] The dome coupler 212 has the same sectional configuration as the inner ends 190 of the dome 182 . As seen in FIG. 14 , dome coupler 212 defines a general I-beam configuration when viewed in longitudinal section. The dome coupler 212 includes a wipe seal 214 which is configured to receive the inner ends 190 of the domes 182 . The wipe seal 214 ensures a secure, weather-resistant connection between the dome coupler 212 and the inner ends 190 of the domes 182 .
[0062] In this embodiment, the domes 182 and the dome coupler 212 are configured to provide a secure, weather-resistant connection with the base 102 , even if the length of the base 102 varies. The dome coupler 212 and wipe seal 214 ensure a weather-tight seal is created with the inner ends 190 of the domes 182 , even if the base 102 is longer than intended.
[0063] While a preferred embodiment has been set forth for purposes of illustration, the foregoing description should not be deemed a limitation of the invention herein. Accordingly, various modifications, adaptations and alternatives may occur to one skilled in the art without departing from the spirit of the invention and scope of the claimed coverage. | A warning light for attachment to a vehicle comprising a thermally conductive longitudinally extending base, a plurality of light head mount assemblies, a plurality of LED warning light assemblies, and a plurality of electronic control circuits. Said base has a pair of generally parallel longitudinal edges and a pair of ribs projecting perpendicularly from said base. Said light head mount assemblies comprise a bracket and a light head retention shoe. Said bracket has a generally planar bracket first portion and a generally planar bracket second portion oriented perpendicular to said first portion. Said light head shoe has a sole configured to engage said bracket first portion, a rib engaging portion, and a brace extending angularly therebetween. Said LED assemblies are mounted on said bracket second portion. Said dome has a main body portion, sidewalls configured to engage said edges, and end walls. | 1 |
BACKGROUND OF THE INVENTION
[0001] Thermoplastic articles, such as bottles that are made using polyethylene terephthalate (PET) are currently made through the use of injection molded pre-forms. Such pre-forms are re-heated and then stretch blow molded into the final bottle shape. The stretching step allows for better orientation of the polymer. However, this process is expensive and time consuming and has other drawbacks that will be explained below. Moreover, the step of injection molding is not practical for use with less expensive resins like polypropylene when bottle design requires blow ratios greater than about 2:1 such as in narrow neck bottles.
[0002] It would be desirable to develop a method for preparing thermoplastic articles such as clear low cost bottles which is faster, less expensive, and suitable for use with less expensive polymers. It would also be desirable to provide a method for producing multi-layer articles.
[0003] These and other objects are achieved by the invention which is described below.
[0004] The following patents are related to the field of the invention.
[0005] U.S. Pat. No. 5,540,879 discloses a method of producing a blow-molded PET container suitable for hot-filling which includes the steps of injection molding a pre-form, blow-molding the pre-form into a primary molded article larger than the desired final container, heating the primary article in a series of oven chambers while its mouth is sealed so that pressure builds within the article to thereby control shrinkage, and blow-molding the shrunken article into the desired container. The two molds are preferably heated, and the mold contact time is as long as allowed by the manufacturing process to help remove internal stresses in the article. An apparatus for carrying out the method includes a first machine having an injection station, a thermal conditioning station, a primary blow-molding station, and an exit station. A second machine includes the oven chambers and a final blow-molding station. The primary article is sealed by a cap member that has a pressure relief valve connected to it to limit the internal pressure during heating, an air supply passage for final blow-molding, and a tensioning rod for insertion into the primary article and engaging a pocket in the center of the article's bottom. In some applications, it is necessary to stiffen the neck, particularly when hot-filling at about 200° F. or higher, or when using a closure roll-on die or a lugged neck finish to apply a bottle cap to the final container.
[0006] U.S. Reissue 029,065 discloses an improved method for forming blow molded articles of enhanced physical characteristics by orienting the material during the formation of the article. A two-stage blowing operation is provided wherein a pre-form blow mold effects a uniform and controllable transfer of heat from a freely extruded tube. The pre-form is conditioned, both thermally and dimensionally, within the pre-form for most effective orientation during a subsequent final blowing operation. Manipulatively, the disclosed method provides a completely overlapped pre-blowing and final blowing operation, and more than one set of pre-blow and final blow molds may be utilized at a single extruder orifice, if desired. Further, the direction and extent of movement of the molds adapts the method to presently existing blow molding machines, while increasing the machine output. Successively utilized blow tubes form and reform the open or blowing end of the tube to a final configuration. In the manufacture of containers, the two successively utilized blow tubes form an accurate, dimensionally stable finish for a bottle while also severing any neck flash from the finish.
SUMMARY OF THE INVENTION
[0007] The invention relates to a process for manufacturing thermoplastic articles such as bottles from a thermoplastic resin which comprises:
[0008] 1) manufacturing a pre-form using extrusion molding;
[0009] 2) stretching and blow molding said pre-form in a secondary step so as to provide the orientation of the polymer, the clarity and the other desired physical properties of the bottle.
[0010] The invention also relates to thermoplastic articles made by the process of the invention, and pre-forms made by processes of the invention.
DESCRIPTION OF THE FIGURES
[0011] [0011]FIG. 1 is a schematic, cross sectional view of a thermoplastic blow molding apparatus for blow molding pre-forms in the process of the present invention.
[0012] [0012]FIG. 2 is a cross sectional view of an apparatus used for stretch blow molding said pre-forms into a finally shaped thermoplastic article in the process of the invention.
DETAILED DESCRIPTION OF THE INVENTION
[0013] As noted above, the process of the invention is for preparing thermoplastic articles such as bottles which:
[0014] (1) comprises manufacturing a pre-form using extrusion blow molding; and
[0015] (2) stretching and blow molding said pre-form in a secondary step so as to provide final shape to said article and to orientate said polymer in said thermoplastic resin so as to obtain said article.
[0016] The invention also relates to the thermoplastic articles so formed. The invention also relates to pre-forms made by the process of the invention.
[0017] As noted above, in the past processes, preparation of the pre-form has been carried out by injection molding, re-heating, and then stretch blow molding. Injection molding involves the use of a core and a cavity which are arranged so as to provide a volume in between. Thermoplastic resin is typically injected, under pressure, and in a molten state, through a gate and a screw and into the volume between the core and the cavity. The thermoplastic resin is allowed to cool and partially harden within the volume, thereby forming a pre-form.
[0018] The final article is then made by removing the pre-form from the core and the cavity (the core and the cavity, taken together, are called the mold), and stretch blow molding it into a larger cavity to form the final article.
[0019] There are a number of limitations to the injection molding process. First, the cost of tooling can be very expensive. Details, such as curves and indentations require the final cavity to be crafted into complementary shapes, with sizes and spacing that fall within very small tolerances, which is expensive to do.
[0020] Second, the injection molding process is usually limited to the preparation of monolayer articles. That is to say, the injection molding process is usually limited to the preparation of articles which have walls which are comprised of only one thermoplastic resin. This is because the arrangement whereby a resin is injected through a screw and a gate into a mold, allows only for one injection of one type of resin.
[0021] Third, the injection molding process for forming the pre-form usually takes a minimum of about 20 seconds from one injection to the next, thereby limiting the speed of production of thermoplastic articles.
[0022] Fourth, the injection molding process can only be used with certain expensive thermoplastic resins such as PET, and cannot be used with inexpensive resins like polypropylene. It is not practical for making narrow neck containers from these inexpensive resins because the blow ratios greater than about 2 . 5 : 1 are difficult to blow from these inexpensive resins.
[0023] In the process of the present invention, the pre-form is prepared by extrusion blow molding rather than by injection molding.
[0024] In extrusion blow molding, a thermoplastic resin is forced by heating and by back pressure from the material moving through the screw which forces the resin through the die which forms the parison. When said thermoplastic resin emerges from the end of said screw or tube, it forms a continous tube which is called a parison. The thermoplastic resin, at this instant, can have the consistency of a thick paste. The parison can then be allowed to cool to some extent and blow molded. That is, the parison is then positioned within a cavity which is complementary in shape to the outer surface of the final thermoplastic article, and a gas such as air is blown into the parison so as to cause it to mold to the inner surface of the cavity, thereby forming the shape of the pre-form. The cavity can then be cooled and the pre-form can be removed. The pre-form can then be inserted onto a blow pin, for example, and can then be made to undergo a stretch and blow molding process so as to form the thermoplastic article in its final shape.
[0025] This extrusion molding; and the stretch and blow molding process of the invention, has numerous advantages.
[0026] First, it allows for the formation of shapes of final articles that are of a greater variety than is possible through the use of injection blow molding, followed by blow molding. This is so, because any pre-form that is made by an injection molding step, cannot be removed from its mold for blow molding, if it has undercuts that exceed about 0.060″ in its shape.
[0027] Second extrusion molding; and the stretch and blow molding process of the invention, allows for the production of multi-wall thermoplastic articles. This is the case because multiple extruders (each has a screw) can by arranged so that each extrudes a different thermoplastic resin into the die that forms the parison. Multiple extruders can be arranged around the die, much as spokes are arranged around the hub of a wheel, with each extruder injecting a different thermoplastic resin into the die which forms the parison.
[0028] Each different thermoplastic resin can form a different layer in the wall of the resulting parison. Put another way, The thermoplastic resin forms a tube as it is forced through the die by the back pressure of the screw(s). The multiple extruders can be arranged so as to form a tube which has, for example, a wall which has an inner layer of one thermoplastic resin, and an outer layer of another thermoplastic resin.
[0029] During blow molding of this parison into its final shape within the cavity, a final article is formed which has a wall which has an inner layer of the one thermoplastic resin and an outer layer of the other thermoplastic resin. An advantage to having such a multi-walled final article is, for example, that you can produce, for example, a bottle which has a chemical resistant inner surface made of ethyl vinyl alcohol (EVOH), and has a high moisture barrier outer surface made of polyolefin such as polypropylene or polyethylene. This advantage forms another part of the present invention.
[0030] Another advantage of the extrusion molding, blow and stretch molding process of the present invention, is that it allows for the use of lower density thermoplastic resins than are typically used in an injection molding process.
[0031] Another advantage of the extrusion molding, blow and stretch molding process of the present invention is that in the final blow molding state, the conditions of manufacture can be arranged so that the strings of polymer molecules within the originally amorphous resin are aligned so as to produce a final clear plastic article. But it should be appreciated that processes of the present invention, and final articles of the present invention, are not limited to clear thermoplastic articles, but can also include, for example, translucent and opaque thermoplastic articles.
[0032] In the process of the present invention, the ratio of the size of the final thermoplastic article to the size of the pre-form can be about 1.5:1 to about 5.5:1 or greater, depending on the thermoplastic resin which is used. The ratio is called the blow ratio. For a given thermoplastic article the blow ratio of the length of the article to the pre-form can differ from the blow ratio of the width of the article to the width of the pre-form. For example, the blow ratio of the length can range from about 2:1 to about 4:1, or greater, or about 2.5:1 to about 4:1 or greater, depending on the resin used and the process has been carried out wherein this blow ratio of length is about 3:1 and between about 2:1. The blow ratio of width can range from about 1.5:1 to about 3.5:1 or greater depending on the resin used, and the process has been carried out wherein the width ratio is about 2.5:1 to about 2.1:1.
[0033] In the process of the invention, the thickness of the wall of the pre-form can range from about 0.060 inches to about 0.200 inches, more preferably about 0.10 inches to about 0.15 inches. An example of a process of the invention has been carried out wherein the thickness of the wall of the pre-form was about 0.125 inches and in another case the wall of the pre-form was about 0.130 inches. An advantage of the process of the present invention is that it allows for the fabrication of pre-form which are formed by injection molding. Therefore, the process of the present invention can be carried out by using less thermoplastic resin, for each article, and thus, the process of the present invention is more economical than the injection blow molding process for forming a pre-form.
[0034] The pre-form can be fabricated so as to have uniform wall thicknesses. By “uniform wall thicknesses” is meant thicknesses which are +0.05 inches to about 0.008 inches, more preferably about +0.010 inches. Uniform wall thicknesses for the pre-form allow the final thermoplastic article to have a uniform wall thickness. Alternatively, when it is desired to have a final thermoplastic article which has walls of differing thicknesses, then this can be accomplished by fabricating the pre-form so as to have walls of differing thickness.
[0035] The amount of time (cycle time) that elapses in the formation of a pre-form can range from about 5 to about 30 seconds, depending on the resin which is employed. An example of a process of the invention has been carried out wherein the cycle time was about 20 seconds and where the cycle time was about 30 seconds. When the resin employed was polypropylene, the extruder temperature was about 450 degrees F. Different resins will be extruded at different temperatures.
[0036] The fabrication of pre-forms using the process of the present invention is typically accomplished more quickly (that is, with a lower cycle time) than is the process of forming a pre-form by injection blow molding. Consequently, the process of the present invention is more economical than processes which employ an injection molding step to form the pre-form.
[0037] The process of the present invention also allows for the use of multiple cavities in the fabrication of the pre-form. This allows for the formation of pre-forms which have varied shapes. Such pre-forms can be blow molded into final thermoplastic articles of varied shapes.
[0038] Any thermoplastic resin which can be extrusion blow molded and then blow molded, can be employed in the process of the present invention. Non-limiting examples of such thermoplastic resins include polypropylene, polyethylene, polyamide, acrylnitrile, or polypropylene. Polypropylene resins which can be employed in the process of the invention include homopolymers and copolymers of polypropylene; and clarified and non-clarified polypropylene. As noted above, fusing the process of the present invention, there can be made multi-layered thermoplastic articles, wherein each layer is comprised of a different thermoplastic resin.
[0039] It will also be appreciated that techniques for handling a pre-form, after it has been fabricated, are known in the art. Such techniques include cooling, trimming, and reaming the pre-form. Techniques for handling the final thermoplastic article include cooling and trimming. The inclusion of such pre-form techniques and thermoplastic techniques does not take a process outside the scope of the present invention.
[0040] It will also be appreciated that depending on the selection of the cavity ether rounded or non-rounded final thermoplastic articles such as bottles may be fabricated.
[0041] Without intending to be bound by the following, it is pointed out that the process of the invention has been carried out to fabricate a closed ended tubular shaped pre-form which had a length of about 4.38 inches, a width of about 1.118 inches in diameter, a wall thickness of about 0.154 inches, a threaded neck (which was not re-heated and stretched in the second stage of the process, and a shoulder. This pre-form was then stretch blow molded in the process of the invention to form a final thermoplastic article which was a cylindrical bottle, with rounded shoulders, which had an opening of about 1.118 inches in diameter, a length of about 8.038 inches, a width of about 2.382 inches, and a uniform wall thickness(+0.010) inches.
[0042] Making reference to the figures of the specification, a detailed description of the manufacture of a clear, plastic article the invention is now provided.
[0043] Specific Processing on Pre-form and Bottle
[0044] Referring to FIG. 1, it can be seen that screw motor, 10 , rotates extruder screw, 12 . As extruder screw, 12 , rotates, raw plastic, 16 , is fed from hopper, 14 , into screw, 12 . Rotation of screw 12 , moves raw plastic, 16 , toward accumulator die head, 26 ,. Heater bands, 18 , are placed along the length of extruder barrel, 20 , which in turn holds extruder screw, 12 .
[0045] Heat from heat bands, 18 , and from back pressure from the extrusion process, itself, transforms raw plastic, 16 , into molten plastic. The molten plastic collects in accumulator die head, 26 . A gas, such as air, is forced through blow pin , 22 , to form parison, 28 .
[0046] Parison, 28 , is then blow molded by blow pin, 22 . A gas, such as air, is forced though blow pin, 22 , and the softened thermoplastic resin of parison, 28 , is thereby made to conform to the inner walls of mold, 30 , thus forming pre-form, 32 , in its final shape.
[0047] Pre-form, 32 , may then be partially cooled, for example, by cooling gas. Pre-form, 32 , may then be removed from blow pin, 22 , and transported by a conveyor belt (not shown) or by other means which are known in the art, to the stretch-blow molding apparatus shown in FIG. 2, where it may be inserted upon stretch-blow pin, 42 . A combination of pushing and blowing, the pre-form, 32 , causes it to conform to the inner wall of mold, 45 , so as to form the thermoplastic article, 46 , in its final shape. The thermoplastic article may be cooled and then stripped from stretch blow pin, 42 . | A process for manufacturing a thermoplastic article which comprises the steps of:
a) extruding one or more thermoplastic resins, with a gas, through a screw and then a gate so as to form a partially soft parison;
b) and then positioning said parison within a cavity which has a shape which is complementary to the shape of the outer surface of said thermoplastic article;
c) and then blow molding said parison onto the cavity to form said thermoplastic article, and cooling said cavity so as to obtain any desired orientation of polymer molecules within one or more thermoplastic layers of the wall of said thermoplastic article. | 1 |
FIELD OF THE INVENTION
[0001] The present invention relates generally to freezers for cryogenic treatment of metals and other materials and, more particularly, to a freezer and plant gas system that harnesses the cooling properties of the plant gas evaporator in a manner that facilitates energy and cryogen savings, as well as, thermal processing automation and optimization.
BACKGROUND OF THE INVENTION
[0002] Recently, substantial attention has been drawn to cryogenic treatment of metal parts and tools. The cryogenic treatment process tends to enhance a metal's mechanical properties such as wear resistance, hardness, and dimensional stability. Manufacturing companies, which replace thousands of worn out tools every year at a tremendous cost to the company and the consumer, are turning to cryogenic treatment processes in growing numbers in an effort to increase tool life and reduce costs. Use of the cryogenic treatment process has also found its way into high performance applications and consumer type products. For instance, cryogenic treatment processes are used to enhance the performance and durability of auto racing cars, the accuracy of firearms, the performance of baseball bats and golf clubs, the tonal quality of musical instruments, and the accuracy of aeronautical measuring devices. It also plays an integral part in the construction of satellites, interplanetary probes, and ground and space based telescopes. Other areas in which the cryogenic treatment process is being used include the fields of medicine, genetics, and semiconductors.
[0003] The cryogenic treatment process typically includes the use of liquid cryogen, such as nitrogen or some other inert gas, to significantly cool parts or specimens well below zero degrees Fahrenheit (F); in some instances, all the way down to minus 320° F. The cooling is typically accomplished in a “cold box” or insulated freezer compartment supplied with a liquid cryogen from a liquid storage tank.
[0004] Most facilities with freezer installations also include plant processes, such as heat treating, that utilize inert gas. To supply gas to these processes, evaporators, which enables the liquid cryogen to expand to gas, are installed near the liquid storage tank, usually on the same pad and typically in “free air” to take advantage of maximum heat exchanging properties. A drawback to placing the evaporators in “free air” is that a significant amount of cooling energy is unnecessarily wasted. Harnessing this energy could prove to be advantageous to overall plant processes and economics.
[0005] Another drawback to established freezer installations is the location of the freezer. Typically, the freezer is installed in the immediate vicinity of the liquid storage tank to ensure liquid is available in a reasonable amount of time when called for in the cooling process. This location may be a significant distance from the location most beneficial to the overall process and economics of a plant. For example, in heat treatment facilities, it may be desirable to locate the freezer on the other side of the plant within an automated thermal processing line, which would allow an operator to include heat treatment and cryogenic treatment in the treatment “recipe” for a given part or tool. However, the farther the freezer is located away from the liquid storage tank, the less efficient the freezer system will operate.
[0006] The inefficiency of the freezer system is due to the expansion of the liquid cryogen to gas within the liquid supply conduit. Specifically, the liquid cryogen will expand into gas in the conduit in which it is transported until the conduit itself is cooled below the temperature at which the cryogen will liquefy or stay in liquid form. The farther the freezer is away from the liquid source, the more gas that will evaporate and expand in the conduit and be wasted in the freezer, until the conduit is cooled and liquid reaches the freezer. Because freezer use is intermittent in most freezer installations, the liquid cryogen will typically re-expand along the conduit as the freezer and conduit warm between cooling processes. As a result, significant quantities of gas will likely be wasted upon each use of the freezer.
[0007] One way to combat this waste is to locate the freezer in the immediate vicinity of the liquid storage tank. But as noted above, this requires locating the freezer remotely from the designed heat/cryogenic treatment process and, thus, creates excessive labor costs due to material handling and transportation to and from the balance of the process. Alternatively, a cryogenic pumping system could be used to provide constant pressure to prohibit expansion of the liquid cryogen to gas in the piping system. However, such systems tend to be very costly to purchase and install, as well as, operate and maintain.
[0008] Thus, it would be desirable to provide a freezer and plant gas system in which the freezer can be located remotely from the liquid storage tank, wherein liquid is supplied to the freezer on demand without excessive wasting of gas, and wherein the cooling energy of the plant gas evaporation process can be harnessed.
SUMMARY OF THE INVENTION
[0009] The present invention is directed to an improved freezer and plant gas system that harnesses the cooling properties of the plant gas evaporator to facilitate energy and cryogen savings, as well as the automation and optimization of a plant thermal processing system. In a particularly innovative aspect of the invention, the freezer includes an internally mounted evaporator sized to meet the gas requirements of the plant processes requiring inert gas. By evaporating the plant gas in the freezer, the freezer can be remotely located from the liquid cryogen source while making liquid cryogen available when called for during a cryogenic treatment process of metal and other materials. In addition, by evaporating in the freezer the freezer advantageously harnesses the cooling properties of the evaporator to pre-cool the freezer and material to be treated prior to any use of liquid cryogen in the cooling process; resulting in significant cryogen and energy savings.
[0010] In another innovative aspect of the invention, a liquid load basket is adapted to economically thermally treat materials in a deep cryogenic treatment process.
[0011] Other innovative aspects of the invention include the preceding aspects individually or in combination.
[0012] Other aspects and features of the present invention will become apparent from consideration of the following description taken in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] [0013]FIG. 1 is a schematic of the plant gas system of the present invention with an isometric view of a cryogenic freezer of the present invention.
[0014] [0014]FIG. 2 is a piping schematic of the plant gas system of the present invention shown if FIG. 1.
[0015] [0015]FIG. 3 is a graph showing liquid cryogen use of the freezer of present invention plotted against the temperature in degrees F. reach inside the freezer.
[0016] [0016]FIG. 4 is an isometric view of a liquid load basket of the present invention for use in deep cryogenic treatment processes.
[0017] [0017]FIG. 5 is a piping schematic of a prior art freezer installation.
[0018] [0018]FIG. 6 is a piping schematic of an alternative embodiment of the plant gas system of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0019] Referring to FIG. 1, a plant gas system 10 of the present invention is shown. The plant gas system 10 includes a liquid storage tank 20 filled with a liquid cryogen, such as nitrogen, argon, or other liquid cryogen, a freezer 30 with an internally mounted plant gas evaporator 40 , and a plant gas reservoir 50 . In operation, liquid cryogen flows from the storage tank 20 into the freezer 30 to be used in a cryogenic treatment process and separately flows through the evaporator 40 where it is evaporated or expanded into gas. The expanded gas flows into the reservoir 50 and from there it is supplied to plant processes that utilize inert gas. By evaporating inside the freezer 30 , the plant gas system 10 of the present invention advantageously captures the cooling energy of the evaporator 40 that is normally lost in established plant gas methods, and economically and efficiently transports liquid cryogen over long distances.
[0020] Although most thermal processing plants have a sizeable inert gas usage for vacuum furnaces, nitrating furnaces, hardening furnaces, etc., only nominal plant gas usage, such as the introduction of vaporized inert gas into the plant's pneumatic system, is needed to cause liquid cryogen to flow to the plant gas evaporator 40 within the freezer 30 where it is expanded into gas. As a result, liquid cryogen tends to be immediately available when called for in the cooling process. More particularly, liquid cryogen tends to be available without having to expel and, therefore, waste significant quantities of warmer gas as the conduit cools to temperatures necessary to liquefy the cryogen. In addition, the cooling properties of the evaporator 40 advantageously pre-cool the freezer 30 and material to be processed prior to the use of any liquid cryogen. Depending on a plant's gas usage, the freezer and material can be pre-cooled to temperatures ranging from about minus 80° F. to about minus 150° F., and possibly lower. Accordingly, there tends to be substantial savings in the amount of liquid cryogen used during the cooling process. The amount of energy in BTU's that it takes to cool the freezer components and material to a desired temperature illustrates that the pre-cooling process saves a significant amount of liquid cryogen.
[0021] For example, the amount of energy (Q) in BTUs that it takes to cool the a load of material can be calculated as follows:
Q=M×S×DELTA-T
[0022] wherein,
[0023] Q=Heat removed in BTU's
[0024] M=Mass in pounds (#s) of material to be cooled
[0025] S=Specific heat of material in BTU's/#/° F.
[0026] DELTA-T=Temperature differential between ambient temperature, which in heat treating facilities is typically 20° F. higher than outside temperatures, and the temperature to which the internal evaporator will cool the freezer compartment, freezer components, and the material to be processed.
[0027] For this calculation, the material and components to be cooled include a 1,000 # load of steel (S=0.12), a stainless steel (S=0.12) freezer load basket with associated components weighing approximately 180#s, and a stainless steel freezer inner wall assembly weighing approximately 350#s. Assuming an ambient temperature of 80° F., and a pre-cooled temperature of minus 100° F.,
[0028] Delta-T=180° F.
[0029] Q Load =M L ×S L ×Delta-T=1,000×0.12×180=21,600 BTU's
[0030] Q Basket =M B ×S B ×Delta-T=180×0.129×180=3,532 BTU's
[0031] Q wall =M W ×S W ×Delta-T=350×0.129×180=6,867 BTU's
[0032] Q Total =31,999 BTU's
[0033] According to this example, pre-cooling would save the amount of liquid cryogen necessary to generate 32,000 BTU's of cooling energy.
[0034] In addition to these savings, evaporating within the freezer 30 allows the freezer 30 to be located anywhere within the plant and preferably where it would be most beneficial to the overall process. More particularly, the ability to locate the freezer in the area of the plant where the balance of the before-and after-freezing processes are performed, enables a system operator to include freezing in the “recipe” for automated and semi-automated systems. This tends to create considerably savings in time and labor cost due to material handling. For instance, locating the freezer within the balance of heat treating equipment allows the same alloy baskets to be used for the hardening furnace, the washer, the tempering furnace and the freezer. Substantial savings in time and labor cost result from not having to transfer material from one basket to another, and back again, and from not having to transport material from the heat treatment line to the freezer, and back again.
[0035] As noted above, by evaporating in the freezer compartment, liquid cryogen tends to be immediately available at the freezer location. This enables better and more stable control of the temperature in the freezer compartment compared to a system that would first produce warmer gas, then liquid, each time the process calls for cooling. Freezer controls normally include an analogue input temperature control system utilizing a PID (proportional-integral-derivative algorithm) loop to open and close a cryogenic solenoid valve or actuate a motor operated valve (MOV) to control the flow of liquid into the insulated freezer compartment. In previous systems, when the PID control calls for cooling it will first encounter warm gas, then liquid. In response, the PID control is likely to over-react as the higher temperature gas being expelled almost instantaneously turns to the considerably lower temperature liquid. By encountering liquid from the outset, a control system employed with the freezer 30 of the present invention will tend to perform more efficiently and be more stable as the system acquires and maintains a desired temperature set point.
[0036] Referring in detail to FIGS. 1 and 2, the freezer 30 and plant gas system 10 of the present invention comprises a liquid cryogen storage tank 20 having primary 21 and secondary 11 liquid conduit lines extending therefrom. The liquid storage tank 20 stores gases such as nitrogen, argon, oxygen, helium, or others, or combinations thereof, in liquid form. Cryogenic globe valves 12 and 22 are installed along the liquid conduit lines 11 and 21 adjacent the storage tank 20 to isolate the tank 20 while it is being filled, repaired, or replaced. Located adjacent the storage tank 20 along secondary line 11 is a tertiary or backup evaporator 13 , which is normally exposed to ambient conditions as in typical plant gas systems. A secondary plant gas supply line 14 extends from the tertiary evaporator 13 and joins a primary plant gas line 42 , which feeds into a gas reservoir 50 . A dual pressure switch 53 on the reservoir 50 causes a solenoid valve 15 in the secondary plant gas line 14 to open and close depending on the gas pressure in the reservoir 50 . Preferably the solenoid valve will open when the pressure in the reservoir 50 goes below 80 pounds and will close when the pressure in the reservoir 50 raises above 95 pounds. The solenoid valve 15 is preferably a normally open-type solenoid valve to ensure plant processes have sufficient gas in the event of a power outage. A pair of isolation ball valves 16 a and 16 b is located on either side of the solenoid valve 15 to isolate the solenoid valve 15 for repair or replacement. A check valve 19 , preferably a swing back type with a Teflon seat, is located along the secondary gas line 14 after the solenoid valve 15 . The check valve 19 prevents back flow of gas from the primary plant gas line 42 along the secondary the plant gas line 14 toward the liquid storage tank 20 .
[0037] A pressure by-pass line 14 a branches around the solenoid valve 15 and includes a pressure actuated valve 18 and a pair of isolation ball valves 17 a and 17 b located on both sides of the pressure actuated valve 18 . As the gas pressure builds up in the liquid storage tank 20 from the evaporation of the liquid cryogen, a pressure relief valve (not shown) would typically vent the gas from the tank 20 into the atmosphere. The bypass line 14 a and valve 18 combat this wasteful method by advantageously allowing the gas to be flow into the gas reservoir 50 .
[0038] The primary liquid cryogenic supply line 21 extends from the liquid storage tank 20 to a freezer 30 of the present invention. The freezer 30 preferably includes an enclosure 30 a having a door 30 b that is opened to insert material for cryogenic treatment, an internally mounted evaporator 40 , a series of sprayer nozzles 33 , a flapper vent 36 to exhaust gas during the cooling process, and a fan 35 to uniformly circulate the cool gas. The freezer enclosure 30 a , which is generally box-like, preferably includes an external steel plating weldment and an internal stainless steel plating weldment. A load rack formed of three inch stainless steel tubing and rollers is preferably included adjacent the base of the enclosure. A pressure actuated ball-type drain closure is located in the floor of the enclosure to allow liquid to drain after the cooling process. A hydraulic cylinder preferably drives the door 30 b of the enclosure 30 a . Alternatively, the door 30 b could be driven by a pneumatic cylinder or a chain and roller type assembly. The design of the load rack and internal mechanical roller assembly, along with the external features, esthetic, mechanical or otherwise, are such that they can be altered or customized to accommodate different manufacturers preferences and/or requirements.
[0039] Because liquid cryogen flows to the freezer's internal evaporator 40 , where it is evaporated into gas for plant processes, the liquid cryogen is economically and efficiently transported over long distances and still made available for immediate use when called for during the cooling process. As a result, the freezer 30 can advantageously be placed remotely at distances well over 400 feet away from the liquid storage tank 20 . Depending on the gas usage of plant, it may be possible to efficiently operate the freezer/plant gas system with minimal insulation around the liquid cryogenic supply line 21 and still maintain liquid flowing through the supply line 21 to the freezer 30 . However, it may be economically desirable to vacuum jacket the supply line 21 to ensure that the freezer 30 harnesses the maximum amount of available cooling energy.
[0040] The liquid supply line 21 branches off adjacent the freezer 30 to sprayer and evaporator feed lines 21 a and 21 b . Prior to branching off to the separate feed lines 21 a and 21 b , the liquid supply line 21 includes a cryogenic ball valve 24 to isolate the freezer 30 for maintenance, repairs, or replacement. A 350 psi pressure relief valve is preferably located along the liquid supply line 21 between isolation valves 22 and 24 .
[0041] Inside the freezer compartment 30 a , the sprayer feed line 21 a branches into two sprayer feed arms 31 and 32 . A series of spiral cone type spray nozzles 33 are connected to the feed arms 31 and 32 . The feed arms 31 and 32 and sprayer nozzles 33 are mounted along with the fan 35 adjacent the ceiling of the freezer compartment 30 a . As liquid cryogen is sprayed from the nozzles 33 , the fan 35 is operated to uniformly circulate cool gas around the material being treated. Prior to entering the freezer compartment 30 a , the sprayer feed line 21 a includes a cryogenic ball valve 25 , a pressure regulator 27 , which prevents the freezer compartment 30 a from becoming over pressurized during the cooling process, a solenoid valve 29 , which controls the flow of liquid cryogen to the spray nozzles 33 located on feed arms 31 and 32 , and a pair of pressure (350 psi) relief valves 26 and 28 preferably located between the isolation valve 25 , the pressure regulator 27 and the solenoid valve 29 . The freezer 30 preferably includes an analogue input temperature control system with a PID loop that includes a temperature control switch 34 . The temperature control switch 34 actuates the solenoid valve 29 between open and closed positions to control the flow of liquid cryogen to the spray nozzles 33 . Alternatively, the controller may be programmed to utilize an analog output in order to variably control a MOV valve that could be used in place of solenoid valve 29 to control the flow of liquid to the spray nozzles 33 .
[0042] The evaporator feed line 21 b includes a cryogenic ball valve 38 prior to entering the freeze compartment 30 a . Pressure (350 psi) relief valves 37 and 39 are preferably located between isolation valves 24 , 25 and 38 , and between isolation valve 29 and the internal evaporator 40 . The internal evaporator 40 is preferably mounted on the back interior wall of the freezer compartment 30 a . Alternatively, the evaporator 40 could be mounted on either side wall or ceiling of the freezer compartment 30 a , or may comprise two (2) or more internal evaporators connected in series or parallel within the freezer compartment 30 a . The internal evaporator 40 , which operates as the primary plant gas evaporator for the plant gas system 10 of the present invention, is preferably connected in series to an externally mounted secondary evaporator 41 . Both evaporators are preferably sized at 125% of plant gas capacity. As the temperature within the interior of the freezer compartment 30 a decreases, the primary/internal evaporator 40 becomes less and less efficient resulting in liquid cryogen flowing out of internal evaporator 40 into the external/secondary evaporator 41 . The secondary/external evaporator 41 is utilized to evaporate any liquid cryogen that exits the primary/internal evaporator 40 .
[0043] A primary gas line 42 extends from the external evaporator 41 to the gas reservoir 50 . Prior to the reservoir 50 and a junction with the secondary gas line 14 , the primary gas line 42 includes a pressure regulator 45 , a check valve 47 , an isolation ball valve 48 , and a pressure (350 psi) relief valve 46 preferably located between the pressure regulator 45 and the isolation valve 48 . The pressure regulator 45 preferably prevents liquid cryogen from being pumped into the reservoir 50 , while the check valve 47 , which is preferably a swing back type with a Teflon seat, preferably prevents back flow of gas from the secondary gas line 14 . Another isolation valve 49 is located along the primary gas line 42 after the junction with the secondary gas line 14 and prior to a gas inlet 51 on the reservoir 50 . The reservoir 50 includes a pressure relief valve 52 and a gas outlet 54 . Another isolation valve 55 is located on the plant gas line 56 , which feeds gas to the plant processes that utilize inert gas.
[0044] A blanket gas line 42 a preferably extends from the primary gas line 42 , just after the external evaporator 41 , back into the freezer 30 . The blanket gas system is activated when the freezer door 30 b is opened and creates a positive gas pressure in the freezer compartment 30 a . The positive gas pressure tends to prevent ambient air from entering the freezer 30 and causing the internal evaporator 40 and other components to ice up. The blanket gas line 42 a includes an isolation ball valve 43 and a solenoid valve 44 , which is actuated by a blanket gas control switch that is triggered by the opening of the freezer door 30 b.
[0045] In operation, plant gas is drawn off of the reservoir 50 through the reservoir outlet 54 causing the cryogen to flow in gas form through the liquid supply line 21 , the primary and secondary evaporators 40 and 41 , and the primary gas line 42 into the gas reservoir 50 , until the liquid supply line 21 cools to a temperature at which the cryogen remains a liquid. Once cryogen is flowing in liquid form through the liquid supply line 21 to the freezer 30 , it will flow through the internal primary evaporator 40 where it will expand into gas for the plant processes. The cooling properties of the internal primary evaporator 40 are harnessed by the freezer 30 to pre-cool the freezer compartment 30 a to approximately minus 100° F. As the interior of the freezer compartment 30 a becomes too cold for the primary evaporator 40 to effectively evaporate the liquid to gas, the secondary external evaporator 41 performs the necessary evaporation. By evaporating remotely at the freezer 30 , liquid tends to be immediately available when called for during the cooling process.
[0046] To begin the cooling process, the door 30 b of the freezer 30 is opened to insert the material to be treated. Opening the door 30 b triggers the solenoid 44 in the blanket gas line 42 a to open and feed blanket gas into the interior of the freezer compartment 30 a . The blanket gas creates a positive pressure within the freezer compartment 30 a and, thus, prevents ambient air from entering the freezer compartment 30 b . A load of material to be processed is then manually loaded, or loaded as part of an automated or semi-automated thermal processing line, into the freezer 30 . Once loaded, the freezer door 30 b is shut and the blanket gas solenoid 44 closes.
[0047] The material is then pre-cooled to a desired temperature or for a desired amount of time by using a pre-cool timer or a thermostat, which can be used to initiate the cooling cycle. Once the material has cooled to a desired temperature, such as minus 100° F., or for a desired period of time, a temperature set-point is read by or entered into the control system. The temperature control switch 34 actuates the sprayer solenoid valve 29 to enable liquid cryogen to flow to and out of the spray nozzles 33 . The circulation fan 35 is also activated to uniformly distribute the cool gas around the material. As the temperature within the freezer compartment approaches the set-point temperature, the temperature control switch 34 modulates the sprayer solenoid valve 29 to acquire and maintain the set-point temperature. The material will be cooled at the set-point temperature for an appropriate amount of time to obtain the desired mechanical properties for the material being treated. After the treatment process is completed, the freezer door 30 b is opened and the blanket gas system activated.
[0048] The control system includes a purge mode that enables a person to safely enter the freezer 30 and work on its internal components. The purge system will only work when the freezer door 30 b is open. When activated, the purge system disables the liquid cryogen supply to the spray nozzles 33 by closing the sprayer solenoid valve 29 , disables the blanket gas system by closing the blanket gas solenoid valve 44 , and activates the fan 35 to vent any residual gas left in the freezer compartment 30 a . The purge system preferably must be manually reset.
[0049] Turning to FIG. 3, a graph is shown in which use of liquid cryogen by the freezer 30 is plotted against the temperature acquired in the freezer compartment 30 a . As shown, the freezer 30 of the present invention does not use any liquid cryogen in a first or pre-cool temperature region (A) as the freezer 30 and material to be treated are cooled from an ambient temperature of approximately 80° F. to a pre-cooled temperature of approximately minus 100° F. In a second temperature region (B), which is between the pre-cooled temperature of approximately minus 100° F. and a transition temperature of approximately minus 225° F., liquid cryogen is sprayed from the nozzles 33 to further cool the freezer 30 and material. The freezer's 30 liquid cryogen use in this temperature region (B) appears to gradually increase as the temperature decreases. The increase in liquid cryogen usage per degree (F) change in temperature in this region (B) is relatively small until the temperature within the freezer 30 nears the transition temperature of approximately minus 225° F. The transition temperature is the temperature at which the freezer 30 tends to begin to use excess liquid for each degree (F) change in temperature. In the third temperature region (C), which includes temperatures at which deep cryogenic treatment is typically conducted, the freezer's liquid cryogen usage appears to increase exponentially for each degree (F) change in temperature as the temperature decreases from the transition temperature to approximately 320° F. While attempting to acquire and maintain a set-point temperature in this region (C), the spray nozzles 33 tend to approach operating at 100% capacity at 100% of the time.
[0050] To more economically accommodate the need for deep cryogenic treatment and avoid wasting liquid cryogen, the freezer 30 of the present invention preferably includes a liquid load basket 70 . As shown in FIG. 4, the liquid load basket 70 includes a generally box-like enclosure 71 mounted on an alloy tray 76 . The enclosure 71 includes an opening 73 at its top to vent expanding gas. The top of the enclosure 71 includes a pair of hingedly connected doors 74 and 75 . Mounted within the enclosure 71 are a series of liquid cryogen level detecting thermocouples 77 a - b corresponding to levels 14 , and a series of off-set level detecting thermocouples 78 a - d corresponding to off set levels 1-4. The basket 70 also includes a liquid feed line or connector 72 to fill the basket 70 with liquid cryogen. The feed line 72 includes a flexible hose with a twist lock type adapter for manual or semi-automatic systems, or a male or female quick disconnect spline-type coupler for fully automatic systems. Although the load basket feed line 72 is connectable to a liquid load connector 60 in the freezer 30 , and the liquid load basket 70 is preferably used in conjunction with the freezer 30 , it is also directly connectable to a source of liquid cryogen.
[0051] As shown in FIG. 2, the liquid load connector 60 is located at the end of a liquid load feed line 21 c , which branches off of the liquid supply line 21 . The liquid feed line 21 c includes an isolation ball valve 57 , a solenoid valve 59 , and a pressure (350 psi) relief valve 58 positioned there between.
[0052] In operation, the material to be processed by deep cryogenic treatment is placed within the liquid load basket 70 . The operator determines at which level the material will be completely submerged in the liquid cryogen and programs the desired level into the control system. The freezer door 30 b is opened and the blanket gas system is activated. The liquid load basket 70 is placed inside the freezer 30 and coupled to the connector 60 on the liquid load feed line 21 c of the freezer 30 . Once the liquid load basket 70 is inside the freezer 30 , the door 30 b closes and the blanket gas is shut off by closing the blanket gas solenoid valve 44 . The liquid load basket 70 is pre-cooled to a desired temperature or for a desired period of time in a manner discussed above. Once the pre-cool temperature is reached or the time runs out, a set point temperature, which preferably equals a temperature that is slightly higher than the transition temperature, is read by or entered into the control system. The temperature control switch 34 then actuates the sprayer solenoid valve 29 sending liquid cryogen to the spray nozzles 33 to acquire the desired set-point temperature within the freezer 30 . As described, the material advantageously goes through two (2) steps of pre-cooling prior to being immersed in the liquid cryogen. The liquid cryogen usage within the liquid load basket 70 will tend to be lower than established methods as a result.
[0053] When the set-point temperature is reached, a fill control switch actuates the sprayer solenoid valve 59 to fill the liquid load basket 70 to a desired level. Assuming for exemplary purposes the set-point level is set at level 2, the control system will allow the basket 70 to fill with liquid until the level 2 off-set thermocouple 78 b , senses a temperature equivalent to the liquid temperature of the cryogen, which is minus 320° F. for nitrogen, indicating that the liquid has reached the level 2 off-set. The fill control switch closes the solenoid valve 59 when the off-set thermocouple 78 b senses the liquid temperature. The control system will maintain the liquid cryogen in the liquid load basket 70 at or above level 2 during the deep cryogenic treatment process by replenishing the liquid as it evaporates. More particularly, when the set-point thermocouple 77 b senses a temperature above the liquid temperature of the cryogen, e.g., minus 319° F. for nitrogen, indicating that the liquid level has fallen below the desired level, the fill control switch opens the solenoid 59 to fill the liquid load basket 70 with liquid cryogen until the off-set thermocouple 78 b again senses the liquid temperature. After the treatment process is completed, the freezer door 30 b can be opened to allow the liquid cryogen in the liquid load basket 70 to evaporate into the atmosphere.
[0054] Alternatively, the liquid load basket 70 may be completely enclosed and include an exhaust gas outlet 80 feeding a gas line 79 , which may advantageously be coupled to a pneumatic gas system reservoir (not shown). In addition, in an attempt to reduce waste, the liquid load basket 70 may advantageously be connected via appropriate piping and valves to a liquid load recycle reservoir (not shown). During the deep cryogenic treatment process, evaporated gas is allowed to freely vent through gas outlet 80 and gas line 79 into the pneumatic gas reservoir. Once the treatment process is completed, a solenoid operated valve (not shown) in the pneumatic gas supply line 79 is closed. As the liquid cryogen in the liquid load basket 70 evaporates into gas, the pressure increases within the basket 70 to a level sufficient to force the remaining liquid cryogen out of the liquid load basket and into the liquid load recycle reservoir. Another solenoid valve (not shown) can be actuated to shut off access to the recycle reservoir when the control system senses that the liquid cryogen has been evacuated from the liquid load basket 70 . The control system preferably includes programming logic that enables the liquid cryogen stored in the recycle reservoir to be used in a subsequent deep cryogenic treatment prior to drawing liquid from the liquid feed supply line 21 c.
[0055] Other alternative embodiments to the present invention include using one gas or combination, for example, oxygen or helium or both, in liquid form, for pre-cooling, i.e., passing the liquid through the freezer's internal evaporator 40 where it is expanded into gas for other uses, and then using another gas or combination, such as nitrogen or argon or both, in liquid form for the cooling process.
[0056] In another alternative embodiment, established freezer installations can be retrofitted to take advantage of the cooling properties of an evaporator and the liquid savings associated with evaporating inside the freezer. An established freezer installation 100 , as shown in FIG. 5, typically includes a liquid storage tank 120 , a supply conduit 121 , and a freezer 130 with spray nozzles 133 . An isolation valve 122 is located adjacent the tank 120 and a control valve 125 is installed in the supply line 121 prior to the freezer 130 to control the flow of liquid into the freezer 130 . To ensure liquid is available at the freezer 130 , a pressure actuated valve 124 is typically installed in the supply line 121 prior to the control valve 125 . The pressure actuated valve 124 is used to vent gas from the supply line 121 to atmosphere (A) until the line 121 is sufficiently cool for liquid to flow. The valve 124 closes when liquid reaches the valve 124 to enable liquid to flow to the freezer 130 .
[0057] Turning to FIG. 6, the pre-cooling benefits and some of the liquid savings of the present invention can easily be taken advantage of by retrofitting the existing installation of FIG. 5. The existing installation 100 can be retrofitted by removing the pressure actuated valve 124 and vent line 124 a and installing an evaporator or heat exchange 140 within the freezer 130 . An evaporator feed line 123 branches off of the supply line 121 and feeds liquid to the evaporator 140 . After the liquid passes through the evaporator 140 , the exiting gas can be vented to atmosphere (A) or to plant or pneumatic gas systems (P). A pressure regulator 126 can be used to vent gas around the evaporator 140 along a by-pass line 128 to exit side of the evaporator 140 until liquid flows through the supply line 121 . A check valve 127 can be installed to prevent the back flow of gas.
[0058] While the invention is susceptible to various modifications and alternative forms, a specific example thereof has been shown in the drawings and is herein described in detail. It should be understood, however, that the invention is not to be limited to the particular form disclosed, but to the contrary, the invention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the appended claims. | An improved freezer and plant gas system that harnesses the cooling properties of the plant gas evaporator to facilitate energy and cryogen savings, as well as the automation and optimization of a plant thermal processing system. The freezer preferably includes an internally mounted evaporator sized to meet the gas requirements of the plant processes requiring inert gas. By evaporating the plant gas in the freezer, the freezer can be remotely located from the liquid cryogen source while still making liquid cryogen available when called for during a cryogenic treatment process metal or other materials. In addition, by evaporating in the freezer the freezer is able to harness the cooling properties of the evaporator to pre-cool the freezer and material prior to use of liquid in the cooling cycle. Alternatively, a liquid load basket is adapted to economically thermally treat materials in a deep cryogenic treatment. | 2 |
This application is a filing under 35 USC 371 of PCT/EP2005/005774, filed May 27, 2005.
BACKGROUND OF THE INVENTION
The invention relates to a method for measuring and/or regulating the oscillation amplitude of an ultrasound oscillator of an ultrasound welding device, comprising components producing and transmitting oscillations in the form of at least one converter and one sonotrode, as well as, if applicable, a booster placed between the converter and the sonotrode, wherein the ultrasound oscillations are produced by transmitting a high frequency voltage coming from a control circuit to the converter. In addition, the invention relates to an ultrasound welding device, comprising components producing and transmitting oscillations in the form of at least one converter and one sonotrode, as well as, if applicable, a booster placed between them, a backing electrode (ambos), between which and the sonotrode compressible, weldable parts, such as wires, are to be placed, preferably in a compression chamber, wherein to the converter for oscillation production an amplitude is transmitted across a control system with high frequency voltage.
In order to obtain reproducible welding results, it is necessary to monitor welding parameters and then, if predetermined target values are exceeded or not met, regulate them. It is thus disclosed in DE-A-198 10 509 to capture ultrasound waves coupling into a welding material following a reciprocal effect with a joined layer as the measuring signal, in order to then further process characteristic parameters by means of a measured data memory and an evaluation unit for the welding process with subsequent control of the sonotrode.
In order to control and regulate the process parameters in the ultrasound welding of plastic parts, DE-A-43 21 874 proposes that the joining force be measured during the welding process to monitor the energy application at a joining location between two parts that are to be welded.
According to EP-B-0 567 426 the oscillation amplitude of a sonotrode welding plastic parts is reduced after a predetermined time interval, in order to then work with a lower oscillation amplitude during the remaining time of the welding operation. An appropriate control signal to reduce the amplitude can also be initiated directly or indirectly as a function of the power transmitted to the work pieces to be welded, as is revealed, for example, in WO-A-1998/49009, U.S. Pat. Nos. 5,855,706, 5,658,408 or 5,435,863.
WO-A-2002/098636 discloses a method for welding plastic parts, in which during an initial time span the oscillation amplitude is reduced following a given course to optimize the welding process, in order to subsequently perform a measurement of a characteristic parameter of the work piece and then, as a function of the value of the parameter measured, end the welding process with a constant amplitude of a sonotrode transmitting ultrasound energy.
In order to check connections established by ultrasonic wire bonding, DE-A-101 10 048 envisions an online monitoring method on the basis of predetermined or stored master values, which allow inferences to be made about the stability of the connection.
An ultrasound welding method for coated electrical wires and a device for performing the method are disclosed in DE-A-102 11 264. In order to vary the welding energy after removal of the insulation and for the welding of the conductors, a measurement of the resistance of the electricity flowing between the sonotrode and the backing electrode is carried out.
SUMMARY OF THE INVENTION
The underlying problem of the present invention is to provide a method of the type named at the outset with which the oscillation amplitude of an ultrasound oscillator can measured and/or regulated in a simple manner.
To solve this problem, the invention essentially provides that a sensor detecting the oscillation amplitude is associated with at least one component of the ultrasound oscillator and that signals corresponding to the oscillation amplitudes determined by this sensor are monitored and/or are compared with the expected signals in the control circuit or the measuring and monitoring device and that, as a function of deviations occurring between the actual and expected signals, the high frequency voltage transmitted to the converter or the transmitted high frequency current is varied. A regulating process takes place.
According to the invention so-called amplitude feedback occurs in order to control the amplitude of the ultrasound oscillator such that reproducible and optimal welding results are attainable.
Amplitude feedback, however, also serves the mutual tuning of different oscillators in order to be able to compensate for possible amplitude deviations between the individual oscillators. In addition, amplitude feedback offers the possibility of compensating for amplitude changes of an ultrasound oscillator which are caused by deterioration.
Limit temperatures at the converter also can be acquired by means of a frequency shift of the operating point and thus be compensated for. Finally, if impermissibly high amplitudes occur, the production of ultrasound oscillation can be interrupted so that safety functions can be satisfied.
In addition there is also the possibility, thanks to the invention, of determining any deterioration of the piezo-ceramic discs producing the oscillations or changes in electrical variables, such as the high frequency voltage signal of the control system, for example of the generator. The load/no-load behavior of the converter can also be detected by means of amplitude feedback.
A piezo-ceramic sensor in particular can be used. It can be integrated into the converter, wherein in addition to the active piezo-ceramic discs, by means of which the ultrasound oscillations are produced, a piezo-ceramic disc is used, from which signals for the purpose of determining the amplitude are produced and accessed, on the basis of the pressure application produced by the other piezo-ceramic discs. An optical detection of the amplitudes, e.g. by means of a laser, however, is also possible. Other sensors, such as ohmic sensors, e.g. elongation measurement tape sensors, acceleration sensors, or acoustic sensors can also be used.
If the sensor is preferably integrated into the converter, there is the possibility of placing a corresponding sensor on or in the booster, on or in the sonotrode, on the converter housing or at a mount or receptacle of the ultrasound oscillator, in order to generate the desired signals and thus allow monitoring or control of the amplitudes.
In order to facilitate optimal amplitude detection and thus feedback, it is provided that the sensor is placed at the maximum oscillation of the component elements, especially the converter. In the process the masse of the sensor should be designed such that a noticeable mass falsification of the component element does not occur. In addition, the sensor should be connected such to the component that the sensor oscillates in tune with the component.
The signals of the sensor can be evaluated in that the alternating signals produced by the sensor are compared with those of the high frequency current and the high frequency voltage source. Here, too, there is the possibility of rectifying the alternating voltage signals obtained from the sensor and to make them available to the control system as direct voltage signals for regulating purposes. In the process the actual value of the direct voltage signals should be between 0 and 10 volts.
In a further development of the invention it is provided that the control signals are present at the input of a differential amplifier with a comparator, that the high frequency current and the high frequency voltage signals of the control system are present at another input of the differential amplifier, and that the output signal of the comparator forms the basis for regulating the high frequency voltage and the high frequency current.
In order to determine the oscillation frequency it is also provided that the sensor signals are sent to a comparator and are transformed into voltage pulses with the oscillation frequency of the signals and then are sent to a counter. In the process the signals can be present at a counter input, e.g., a PLC control system.
The invention is in particular also characterized by an ultrasound welding device of the type named at the outset, wherein a sensor detecting the amplitude is associated with at least one component element. This sensor in particular is a piezo-ceramic sensor. A capacitive or inductive sensor, a resistance sensor, such as an elongation measurement strip sensor, an optical sensor, or an acceleration sensor can also be used. Independently thereof, the sensor can be positioned on or in the converter, on or in the booster, on or in the sonotrode, in a housing surrounding the converter, or at a mount of the ultrasound oscillator. A sensor can also be placed on the basic body of the welding module and at the receptacle for the oscillator and the compression chamber. In this case, the sensor for detecting the amplitude is a contactless sensor, such as an optical sensor.
Preferably, however, a piezo-ceramic sensor is used. The invention is also characterized by an ultrasound welding device, in which the converter comprises several first piezo-ceramic discs able to be put into oscillation, which discs are placed between a converter nut and a pin and are tensioned between them by a first bolt element, which protrudes over the outer surface of the resonator body, wherein the first bolt element comprises a tapped blind hole starting at the front area running from the converter nut side, into which hole a second bolt element can be screwed, with which the piezo-ceramic sensor is tensioned in relation to the first bolt. In the process the piezo-ceramic sensor comprises in particular two piezo-ceramic breaker plates, each of which has an outer diameter AD of 15 mm≧AD≧10 mm and/or an inner diameter ID of 8 mm≧ID≧4/mm and/or a thickness D of 1.5 mm≧D≧0.5 mm. The electrodes needed to acquire the signals and running on the respective outer area of the piezo-ceramic breaker discs are preferably baked silver electrodes. In the process the outer electrodes have a ground voltage.
BRIEF DESCRIPTION OF THE DRAWING
Further details, advantages and characteristics of the invention result not only from the claims, the characteristics revealed in them by themselves and/or in any combination, but also from the following description of preferred embodiments shown in the drawings.
Seen are:
FIG. 1 : A principle depiction of an ultrasound welding device with periphery,
FIG. 2 : A first embodiment of a converter with sensor,
FIG. 3 : A second embodiment of a converter with sensor,
FIG. 4 : A third embodiment of a converter with sensor,
FIG. 5 : A booster with a sensor,
FIG. 6 : A sonotrode with sensor,
FIG. 7 : A cutout of a converter,
FIG. 8 : Signal curves,
FIG. 9 : A first evaluation circuit,
FIG. 10 : A signal obtained from the first evaluation circuit,
FIG. 11 : A second evaluation circuit,
FIG. 12 : A signal obtained from the second evaluation circuit,
FIG. 13 : A third evaluation circuit, and
FIG. 14 : A signal obtained from the third evaluation circuit.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1 is a basic depiction of an arrangement for welding parts, in particular wires, by ultrasound. The arrangement comprises an ultrasound welding device or machine 10 , which includes in the usual manner a converter 12 and a sonotrode 14 as well as a backing electrode or ambos 15 associated therewith. In the embodiment, a booster 16 is placed between the converter 12 and the sonotrode 14 , above which the ultrasound oscillator 17 is placed, which consists of the converter 12 , the sonotrode 14 and the booster 16 . The backing electrode 15 associated with the sonotrode 14 or its sonotrode head comprising a welding area can be constructed in several parts, as disclosed in U.S. Pat. Nos. 4,596,352 or 4,869,419, in order to provide a compression chamber with an adjustable cross-section in which the elements to be welded, such as the wires, are placed.
The converter 12 is connected via a line 18 to a generator 20 , which is in turn connected by a line 22 with a computer 24 . A high frequency voltage from the generator 20 is transmitted to the converter 12 , i.e. to the piezo-ceramic discs located therein, in order to expand or contract the discs accordingly, thus producing ultrasound oscillations with an amplitude, which are transmitted via the booster 16 to the sonotrode 14 .
In order to be able to detect and monitor the amplitude or, if necessary, regulate the desired expected values, so-called amplitude feedback occurs according to the invention, i.e., the amplitude of a component element of the ultrasound oscillator 17 , i.e. the converter 12 and/or the booster 16 and/or the sonotrode 14 , is measured and fed back to the control system 20 in order to compare the measured actual amplitudes with the expected amplitude values or expected amplitude ranges stored in the computer 24 . Expected amplitude range means a bandwidth of properly evaluated expected amplitudes. If actual amplitude is above or below the expected amplitude bandwidth, then a readjustment of the high frequency voltage can occur in the generator present in the control system 20 , in order to change the actual amplitude.
In order to detect the amplitude, i.e. to associate a sensor with a component element of an oscillator system 15 , there are a variety of possibilities, of which several are illustrated, for example, in FIGS. 2 to 6 .
Preferably a sensor 26 is integrated or placed in or on the converter 12 . The sensor 26 can be a piezo-ceramic sensor, which is positioned in the converter 12 together with the additional piezo-ceramic discs 28 , 30 , 32 and 34 present, to which a high frequency voltage is applied in the known manner in order to produce the ultrasound oscillations with the desired amplitude and desired frequency by means of expansion or contraction of the piezo-ceramic discs 28 , 30 , 32 and 34 . As a result, the discs 28 , 30 , 32 and 34 are active parts, while the sensor 26 is designated as a passive part, since a high frequency signal is produced by the pressure conveyed to the sensor 26 from the discs 28 , 30 , 32 and 34 , which signal provides information about the amplitude.
In the embodiment of FIG. 3 , a sensor 36 is placed on the back end face of the converter 12 , namely on the outside at the resonator or converter nut, and is tensioned by it in order to produce a signal as a function of the oscillation amplitudes produced by the discs 28 , 30 , 32 and 34 .
A sensor 38 can also be positioned in the pin of the converter 12 , as shown in FIG. 4 .
If it is preferred to place the sensor in or on the converter, it is also possible to integrate a sensor 40 in the booster 16 , as shown in FIG. 5 .
A corresponding design can also occur with respect to the sonotrode 14 . According to the drawing depiction of FIG. 6 , a preferably piezo-ceramic disc is tightened as a sensor 42 in the sonotrode 14 , i.e. between sections 44 and 46 , wherein the sensor 42 defines a plane extending vertically to the oscillator longitudinal axis, as in the embodiments of FIGS. 2 to 5 .
If, as mentioned, a piezo-ceramic sensor is preferred as the amplitude sensor, other sensors are nonetheless equally suitable. For example, inductive sensors, capacitive sensors, optical sensors, such as laser sensors, acoustic sensors, acceleration sensors or resistance sensors, such as measurement tape sensors, can be mentioned.
FIG. 7 is a basic depiction of the arrangement of a piezoelectric sensor 48 , which in the embodiment comprises two piezo-ceramic breaker plates 50 , 52 that are delimited in the known manner by electrodes, which are not explained in more detail, in order to be able to access signals, which correspond to the oscillation amplitude of a converter 54 of an ultrasound welding device, as can be seen in FIG. 1 .
The converter 54 in the embodiment comprises four first piezo-ceramic breaker plates 56 , 58 , 60 , 62 on which a high frequency voltage coming from the generator, i.e. the control system 20 , is present in order to expand or contract the discs 56 , 58 , 60 , 62 , thus producing oscillations of a desired amplitude. The piezo-ceramic breaker plates 56 , 58 , 60 , 62 are tensioned between a so-called converter pin 66 , which is connected to a booster or directly to a sonotrode, and a converter 68 —also called a resonator—via a first bolt element 70 . In this respect, however, reference is made to sufficiently known constructions. The bolt 70 protrudes beyond a converter nut 68 and has a tapped blind hole 74 starting at its end face 72 with internal threading into which a second bolt 76 is screwed, via which the piezo-ceramic breaker plates 50 , 52 are tensioned between the end face 72 of the first bolt 70 and a nut 78 . The sensor 48 formed from the piezo-ceramic discs 50 , 52 runs in the maximum oscillation of the converter 54 and is frictionally connected thereto in such a manner via the two bolts 76 , that an oscillation occurs in tune with the converter 54 .
If the first piezo-ceramic breaker plates 56 , 58 , 60 , 62 are designated as active component parts via which the oscillations in the converter 54 are produced, then the second piezo-ceramic breaker plates 50 , 52 are passive components, since signals are produced with them as a function of the amplitude of the converter 54 and are sent to an evaluation unit in order to regulate the high frequency voltage present on the piezo-ceramic discs 56 , 58 , 60 , 62 such that the converter 54 has the desired amplitudes, which in turn facilitate definite inferences about the amplitude of the booster or the sonotrode of the oscillator system.
In the process, the output signals of the sensor 48 can be calibrated in that the amplitude of the converter 54 is determined, for example, by means of a laser, and the output signal of the sensor 48 is calibrated to a standardized signal. Appropriate values can then be stored on a chip, which is associated with the oscillator or the converter 54 or is attached thereto.
The fact that signals accessed from the sensor allow direct statements to be made about the amplitudes of the converter 54 can be seen in principle in FIG. 8 . There a high frequency current measurement curve 80 , which corresponds to the high frequency current flowing to the converter, and a curve 82 , which corresponds to the signals of the sensor 48 , are depicted. A direct comparison shows that the course of the curve of the sensor 48 can definitely be associated with the course of the curve of the high frequency current.
In order to evaluate the sensor signals, there are a variety of possibilities, of which some examples are shown in FIGS. 9 to 14 .
In the process, a differential amplifier 84 with a comparator can be used for signal evaluation. Present at the inputs 86 , 88 of the differential amplifier 84 are the sensor signals or high frequency current or voltage signals of the generator. The signals are compared and in the event of an impermissible deviation a signal is produced, which can be evaluated by the control system circuit. In the process, a signal shape develops, which corresponds to that of FIG. 10 . The signals obtained are then applied to the digital input of a control system in order to regulate the high frequency voltage or the high frequency current, which is present at piezo-ceramic discs 56 , 58 , 60 , 62 and flows to the converter.
There is also the possibility of evaluating the control signals by means of a rectifier circuit 90 , as can clearly be seen in FIGS. 11 and 12 . An analog direct voltage signal ranging between 0 and 10 volts is produced via the rectifier 90 and can be evaluated by the control system. The corresponding signal is then sent to an analog input of a control system of the high frequency voltage or the high frequency current.
To determine the oscillation frequency of the converter 54 , the control signal can be present with hysteresis at an input 92 of a comparator 94 . To determine the oscillation frequency, the sensor signal is transformed into pulses with the oscillation frequency and is sent to a counter input of a control system, such as a PLC control system. | The invention relates to a method for measuring and/or regulating the oscillation amplitude of an ultrasound oscillator of an ultrasound device. In order to be able to measure or regulate the oscillation amplitude of the ultrasound oscillator in a simple manner, it is proposed that a sensor capturing the oscillation amplitude be associated with at least one component element of the ultrasound oscillator. | 1 |
BACKGROUND
1. Technical Field
The present disclosure relates to a process for coating an article and a method for making the coated article.
2. Description of Related Art
Die steel is widely used in forging, stamping, cutting, die-casting and other tool-making processes. The die steel is usually required to be oxidation-resistant at high temperatures. Typically, physical vapor deposition technology has been used to manufacture coatings which are oxidation-resistant. A coating of transition metal nitride and carbide is one of the most popular choices for the surface hardening material of the die steel due to its high hardness and good chemical stability. However, there are some defects, such as high brittleness, high residual stress and poor adhesion with the substrate. When the temperature of die steel is high, a coating of transition metal nitride and carbide may nevertheless be subject to oxidization.
Therefore, there is room for improvement within the art.
BRIEF DESCRIPTION OF THE FIGURE
Many aspects of the process for coating an article and the method for making the coated article can be better understood with reference to the following drawings. The components in the drawings are not necessarily drawn to scale, the emphasis instead being placed upon clearly illustrating the principles of the coated article and the method. Moreover, in the drawings, like reference numerals designate corresponding parts throughout the several views. Wherever possible, the same reference numbers are used throughout the drawings to refer to the same or like elements of an embodiment.
FIG. 1 is a cross-sectional view of an exemplary embodiment of a coated article;
FIG. 2 is a schematic view of a vacuum sputtering device used in the coating process to create the coated article in FIG. 1 .
DETAILED DESCRIPTION
FIG. 1 shows a coated article 10 according to an exemplary embodiment. The coated article 10 includes a substrate 11 , a base layer 13 formed on the substrate 11 , a chromium oxynitride (CrON) layer 15 formed on the base layer 13 and a silicon nitride (SiN) layer 17 formed on the CrON layer 15 .
The substrate 11 may be made of stainless steel or die steel.
The base layer 13 is a layer of chromium. An vacuum sputtering process may form the base layer 13 . The base layer 13 has a thickness of approximately 0.1 micrometers (0.1 μm) to 0.2 μm.
An vacuum sputtering process may be used to form the CrON layer 15 . The CrON layer 15 has a thickness of about 0.5 μm to 1.5 μm. The CrON layer 15 is composed of small nanocrystals with a very small gap between the crystals, thus the Cr—O—N layer 15 is dense enough to delay the penetration of outside oxygen through to the substrate 11 .
An vacuum sputtering process may be used to form the Si—N 17 . The silicon nitride layer 17 has high hardness and good wear resistance, thus effectively protecting the Cr—O—N layer 15 . The silicon nitride layer 17 has a thickness of about 0.5 μm to 1.0 μm.
The CrON layer 15 and silicon nitride layer 17 can protect the substrate 11 from oxidizing at high temperature, which effectively prolongs the service life of the coated article 10 .
FIG. 2 shows a vacuum sputtering device 20 , which includes a vacuum chamber 21 and a vacuum pump 30 connected to the vacuum chamber 21 . The vacuum pump 30 is used for evacuating the vacuum chamber 21 . The vacuum chamber 21 has a number of chromium targets 23 , a number of silicon targets 24 and a rotary rack (not shown) positioned therein. The rotary rack is rotated as it holds the substrate 11 (circular path 25 ), and the substrate 11 revolves on its own axis while it is moved along the circular path 25 .
A method for making the coated article 10 may include the following steps:
The substrate 11 is pretreated, the pre-treating process may include the following steps:
The substrate 11 is positioned in an ultrasonic cleaning device (not shown) which is filled with ethanol.
The substrate 11 is plasma cleaned. The substrate 11 is positioned in the rotary rack of the vacuum chamber 21 . The air in the vacuum chamber 21 is evacuated to about 3.0×10 −5 Pa. Argon (Ar) gas, having a purity of about 99.999%) is used as sputtering gas and is fed into the vacuum chamber 21 at a flow rate of about 500 standard-state cubic centimeters per minute (sccm). A negative bias voltage in a range of about −200 volts (V) to −500 V may be applied to the substrate 11 , and high-frequency voltage is introduced in the vacuum chamber 21 and the Ar gas is ionized into plasma. The plasma strikes the surface of the substrate 11 to clean the surface of the substrate 11 . The plasma cleaning of the substrate 11 may take between 3 and 10 minutes. The plasma cleaning process will enhance the bonding between the substrate 11 and the base layer 13 .
The base layer 13 is vacuum sputtered onto the pretreated substrate 11 . The vacuum sputtering of the base layer 13 is implemented in the vacuum chamber 21 . The vacuum chamber 21 is evacuated to about 8.0×10 −3 Pa and heated to between about 100° C. and 150° C. Ar gas is used as the sputtering gas and is fed into the vacuum chamber 21 at flow rates of about 150 sccm to 200 sccm. The chromium targets 23 are subjected to between about 8 kw and 10 kw of electrical power. A negative bias voltage between about −150V and −250V is applied to the substrate 11 and the duty cycle is about 50%. The depositing of the base layer 13 may take about 5 to 10 minutes. The base layer 13 has a thickness of about 0.1 μm to 0.2 μm.
The CrON layer 15 is vacuum sputtered onto the base layer 13 . The vacuum sputtering of the CrON layer 15 is implemented in the vacuum chamber 21 . Oxygen (O 2 ) and nitrogen (N 2 ) are used as reaction gases and these are fed into the vacuum chamber 21 at flow rates of about between 40 sccm and 80 sccm and about 30 sccm and 60 sccm, respectively, otherwise the conditions are the same as for the vacuum sputtering of the base layer 13 . The depositing of the CrON layer 15 takes between about 30 min and 60 min. The CrON layer 15 is formed by a magnetron sputtering process and has a thickness of about 0.5 μm to 1.5 μm.
The silicon nitride layer 17 is vacuum sputtered onto the CrON layer 15 . The vacuum sputtering of the silicon nitride layer 17 is implemented in the vacuum chamber 21 . Nitrogen is the reaction gas and is fed into the vacuum chamber 21 at flow rates of about 60 sccm to 120 sccm, and Ar gas is used as the sputtering gas, being fed into the vacuum chamber 21 at flow rates of about 150 sccm to 200 sccm. The silicon targets are subject to from about 4 kw to 6 kw of electrical power. And the duty cycle is about 50%. A negative bias voltage of about −30 V to −50 V is applied to the substrate 11 . The depositing of the silicon nitride layer 17 may takes about 1 hour to 2 hours. The silicon nitride layer 17 has a thickness of about 0.5 μm to 1.0 μm.
EXAMPLES
Some experimental examples of the present disclosure are described as follows.
Example 1
The vacuum sputtering device 20 in example 1 is a medium frequency magnetron sputtering device (model No. SM-1100H) manufactured by South Innovative Vacuum Technology Co., Ltd.
The substrate 11 is made of 316 stainless steel.
Plasma cleaning: Ar gas is fed into the vacuum chamber 21 at a flow rate of about 500 sccm. A negative bias voltage of about −500 V is applied to the substrate 11 . The plasma cleaning of the substrate 11 took 10 min.
Sputtering to form the base layer 13 : The vacuum chamber 21 is heated to about 120° C. Ar gas is fed into the vacuum chamber 21 at a flow rate of about 150 sccm. The chromium targets 23 are subjected to about 9 kw of electrical power and a negative bias voltage of about −200 V is applied to the substrate 11 . The depositing of the base layer 13 took about 5 min. The base layer 13 had a thickness of about 0.1 μm.
Sputtering to form the CrON layer 15 : Oxygen and nitrogen are fed into the vacuum chamber 21 at flow rates of about 80 sccm and 60 sccm, respectively; otherwise conditions are the same as for the vacuum sputtering of the base layer 13 . The depositing of the CrON layer 15 took about 30 min. The CrON layer 15 had a thickness of about 0.5 μm.
Sputtering of the silicon nitride layer 17 : Ar gas and nitrogen are fed into the vacuum chamber 21 at flow rates of about 150 sccm and 120 sccm, respectively. The silicon targets 24 are subjected to 4 kw of electrical power and a negative bias voltage of about −50 V is applied to the substrate 11 . The depositing of the silicon nitride layer 17 took about 60 min. The silicon nitride layer 17 had a thickness of about 0.5 μm.
Example 2
The vacuum sputtering device 20 used in example 2 is the same in example 1.
The substrate 11 is made of 316 stainless steel.
Plasma cleaning: Ar gas is fed into the vacuum chamber 21 at a flow rate of about 500 sccm. A negative bias voltage of about −500 V was applied to the substrate 11 . The plasma cleaning of the substrate 11 took about 10 min.
Sputtering to form the base layer 13 : The vacuum chamber 21 is heated to about 120° C. Ar gas is fed into the vacuum chamber 21 at a flow rate of about 150 sccm. The chromium targets 23 are subjected to about 8 kw of electrical power. A negative bias voltage of about −200 V was applied to the substrate 11 . The depositing of the base layer 13 took about 10 min. The base layer 13 had a thickness of about 0.2 μm.
Sputtering of the CrON layer 15 : Oxygen and nitrogen are fed into the vacuum chamber 21 at flow rates of about 40 sccm and 30 sccm, respectively; other experiment conditions is the same with vacuum sputtering of the base layer 13 . The depositing of the CrON layer 15 took about 60 min. The CrON layer 15 had a thickness of about 1.0 μm.
Sputtering to form the silicon nitride layer 17 : Ar gas and nitrogen are fed into the vacuum chamber 21 at flow rates of about 150 sccm and 80 sccm, respectively. The silicon targets are subjected to about 5 kw of electrical power and a negative bias voltage of about −50 V was applied to the substrate 11 . The depositing of the silicon nitride layer 17 took about 90 min. The silicon nitride layer 17 had a thickness of about 0.8 μm.
Results of the Above Examples
The coated articles 10 made in examples 1 and 2 were subjected to a high-temperature oxidation test and an abrasion test.
High-temperature oxidation test: a tube furnace applied a heating rate was 10° C./min, heating temperature was about 800° C., the holding time was about 10 h. The coated articles 10 made in example 1 and 2 both displayed no oxidation and no peeling.
Abrasion test: a linear wear tester applied a load of about 1 kg, the stroke length was 2.0 inch, the wear rate was 25 times/min. The coated articles 10 made in example 1 and 2 both showed no peeling after 1 min.
It is believed that the exemplary embodiment and its advantages will be understood from the foregoing description, and it will be apparent that various changes may be made thereto without departing from the spirit and scope of the disclosure or sacrificing all of its advantages, the examples hereinbefore described merely being preferred or exemplary embodiment of the disclosure. | A process for coating articles is provided. The coated article includes a substrate, abase layer formed on the substrate; a chromium oxynitride layer formed on the base layer; and a silicon nitrogen layer formed on the chromium oxynitride layer. The chromium oxynitride layer and silicon nitride layer protect the substrate from oxidizing at high temperatures, extending the life of the coated article. A method for making the coated article is also described. | 2 |
SUMMARY OF THE INVENTION
[0001] The present invention relates to the use of pharmaceutically acceptable acetylcholin sterase inhibitors for th preparation of a pharmaceutical composition for treatm nt of fatigue syndromes, particularly chronic fatigue syndrome, such as Chronic Fatigue Syndrome (CFS), Post-infectious Fatigue Syndrome, fatigue associated with human immunodeficiency virus infection and related syndromes such as fatigue associated with pre-eclampsia. Preferably, the cholinesterase inhibitors are selected from a group of nicotinic acetyl-cholinesterase inhibitors such as galanthamine-hydrobromide, which are able to cross the blood brain barrier in humans.
DETAILED DESCRIPTION OF INVENTION
[0002] Fatigue syndrome is Fatigue syndrome designates a condition where fatigue (or synonyms thereof including tiredness and weariness) is considered to be the principal symptom of uncertain cause, i.e. that no recognised underlying disease causes the fatigue. Fatigue is commonly reported as having two aspects, namely mental fatigue and physical fatigue, where mental fatigue is a subjective sensation characterized by lack of motivation and of alertness and physical fatigue is the feeling as lack of energy of strength and is often felt in the muscles.
[0003] To be regarded as a symptom, fatigue must be complained of, and should affect the person's functioning and be disproportionate to exertion. Furthermore, it should represent a clear change from a previous state and be persistent, or, if intermittent, should be present more than 50% of the time.
[0004] Fatigue should be distinguished from low mood and from lack of interest. The symptom of fatigue should not be confused with impairment of performance as measured by physiological or psychological testing. The physiological definition of fatigue is a failure to sustain muscle force or power output.
[0005] Fatigue syndromes have only recently been considered as “real” independent diseases and not only as being caused by an underlying disease or being complaints from neurotics or hypochondriacs. There is an increasing interest for finding the cause of the fatigue in order to find a medical treatment. However, an effective medical treatment for fatigue syndromes has not been available until now.
[0006] The study of fatigue performed by the present inventor indicates that the mechanism of fatigue could be an imbalance in the cholinergic nicotinic transmitter system, both peripherally and centrally, actually a decrease of acetylcholine in the central and peripheral synapses. This is supported by the facts that several of the symptoms often related to a fatigue syndrome are also thought to be caused by decrease of acetylcholine, the other symptoms being, e.g. disturbances of sleep.
[0007] The fatigue and the other symptoms of the syndromes are contemplated to result from an augmentation of the acetylcholinesterase in the synapsis which decreases the amount of synaptic acetylcholine, which decrease is a physiological response to infections and inflammations (sterile infections) because inflammations and infections cause a decrease in the Ca 2 + concentration and as explained below, the result in a decrease in the amounts of acetylcholine released from the presynaptic membranes.
[0008] EP 098 975 discloses a biostimulant tonic which comprises, as the active biostimulants, creatine and hydrolyzate of protein. The biostimulant contains 40 to 45% by weight of creatine, 42 to 46% by weight of calcium-magnesium salt of inositephosphoric acid, 10 to 12% by weight of lyophilized hydrolysate of Royal Jelly, and 1 to 3% of galanthamine. The present invention does not encompass such tonic. EP 098 975 does not describe any phenomenon which corresponds to fatigue syndrome.
[0009] Cholinergic system
[0010] Many cell membranes can be excited by specific chemical or physiological stimuli. The common features of these processes and others carried out by excitable assemblies are:
[0011] 1) The stimulus is detected by a highly specific protein receptor, which is an integral component of the excitable membrane.
[0012] 2) The specific stimulus elicits a conformational change in the receptor. As a result, the permeability of the membrane or the activity of a membrane-bound enzym changes. Many of th responses are highly amplified.
[0013] 3) The conformational changes in the receptor and the resulting alterations in function ar reversible.
[0014] There are mechanisms that take the receptor back to its resting stat and restore its excitability.
[0015] Nerve cells interact with other nerve c lls at junctions called synapses. Nerve impuls s ar communicated across most synapses by chemical transmitters, which are small, diffusable molecules such as acetylcholine and norepinephrine. Acetylcholine is also the transmitter at motor end plates (neuromuscular junctions), which ar the junctions between nerve and striated muscle.
[0016] The presynaptic membrane of a cholinergic synapse, that is one that uses acetylcholine as the neurotransmitter, is separated from the postsynaptic membrane by a gap of about 500 Å, called the synaptic cleft. The end of the presynaptic axon is filled with synaptic vesicles containing acetylcholine. The arrival of a nerve impulse leads to the release of acetylcholine into the cleft. The acetylcholine molecules then diffuse to the postsynaptic membrane, where they combine with specific receptor molecules. This produces a depolarization of the postsynaptic membrane, which is propagated along the electrically excitable membrane of the second nerve cell. Acetylcholine is hydrolyzed by acetylcholinesterase and the polarization of the postsynaptic membrane is restored.
[0017] Acetylcholine is synthesized near the presynaptic end of axons by the transfer of an acetyl group from acetyl CoA (Co-enzyme A) to choline. Some of the acetylcholine is taken up by synaptic vesicles, whereas the remainder stays in the cytosol. A cholinergic synaptic vesicle, which is typically 400 Å in diameter, contains about 10 4 acetylcholine molecules.
[0018] Acetylcholine is released from the presynaptic membrane in form of packets containing of the order of 10 4 molecules. The number of packets release depends on the potential of the presynaptic membrane. In other words the release of acetylcholine is an electrically controlled form of secretion.
[0019] Release of acetylcholine depends on the presence of Ca 2 + in the extracellular fluid. The depolarization of the presynaptic membrane leads to the entry of Ca 2 + , which promotes a transient fusion of the synaptic vesicle membrane and the presynaptic membrane.
[0020] If the concentration of Ca 2 + is decreased, the presynaptic action potential releases fewer packets of acetylcholine; the number released depends on the Ca 2 + concentration. The size of the packets released are the same, it is the amount of packets that are depending on the Ca 2 + concentration. Thus, the amplitude of the potential of the postsynaptic membrane is depending on the Ca 2 + concentration in the surroundings of the presynaptic membrane.
[0021] The depolarizing signal may be switched off to restore the excitability of the postsynaptic membrane. Acetylcholine is hydrolyzed to acetate and choline by acetylcholinesterase. Acetylcholinesterase is located in the synaptic cleft, where it is bound to a network of collagen and glycosaminglycans derived from the postsynaptic cell. The 260-kdal enzyme, which has an α 2 β2 structure, can be readily separated from the acetylcholine receptor.
[0022] Acetylcholinesterase has a very high turnover number of 25,000s −1 , which means that it cleaves an acetylcholine molecule in 40 μsec. The high turnover number of the enzyme is essential for the rapid restoration of the polarized state of the postsynaptic membrane. Synapses can transmit 1,000 impulses per second only if the postsynaptic membrane recovers its polarization within a fraction of a millisecond.
[0023] Acetylcholine reacts with a specific serine residue at the active side of acetylcholinesterase to form a covalent acetyl-enzyme intermediate, and choline is released. The acetyl-enzyme intermediate then reacts with water to form acetate and regenerate the free enzyme.
[0024] Postsynaptic acetylcholine receptors may be assigned to two classes which are clearly pharmacologically distinguishable. Receptors that can be stimulated by nicotine are of the nicotinic type and may be blocked by curare, and receptors that can be stimulated by muscarine are of the muscarinic type and are insensitive to curare. In the autonomic nervous system, the nicotinic receptors are found in the ganglia whereas the muscarinic receptors are found in the effector organs.
[0025] Acetylcholinesterase is found at postsynaptic membranes, but also in the erythrocytes and in the plasma (so-called un-specific acetylcholinesterase or pseudo-cholinesterase or butyrylcholinesterase).
[0026] Acetylcholinesterase inhibitors enhance the effect of acetylcholine by inhibiting its hydrolyzation or at least prolonging the actual time that each acetylcholine molecule is present in the synapse. Cholinesterase inhibitors are of course understood as synonymous to anticholinesterase, and may be understood as a cholinesterase agonist.
[0027] Cholinergic synapses are found in the motor end plates (neuromuscular junctions), in the sympathetic part of the autonomic nervous system in all ganglionic synapses, at the synapses in the adrenal medulla, and at the postsynaptic synapses in the sweat glands. In the parasympathetic autonomic nervous system acetylcholine is the transmitter in all the ganglia as well as at postganglionic effector synapses. Furthermore, acetylcholine is present in the central nervous system where it is contemplated to function as a transmitter.
[0028] The therapeutic need for compounds capable of treating the fatigue syndrome has been increased with the understanding of the fatigue syndromes.
[0029] It has now been found that on administration of galanthamine, a cholinesterase inhibitor, the fatigue disappears, th time for disappearance of the fatigue generally being proportionate to the time th fatigue has lasted.
[0030] The present invention is based on th above-mentioned discovery and relates to the us of a cholinesterase inhibitor for the preparation of a pharmaceutical composition for the treatment of fatigue syndromes, such as severe fatigu syndromes, in particular Chronic Fatigue Syndrome, Post-infectious Fatigue Syndrome, fatigue associated with human immunodeficiency virus (HIV) infection, or fatigue related to preeclampsia. The cholinesterase inhibitor is preferably one which crosses the blood-brain barrier and furthermore is selective with respect to cholinergic nicotinic receptor sites, such as galanthamine hydrobromide.
[0031] A cholinesterase inhibitor is understood as being a synonym to an anticholinesterase, and furthermore, to be understood as an cholinergic agonist or a cholinergicum.
[0032] In the present context, the term “a syndrome” designates a complex of symptoms which appear so regularly together that it is contemplated that they are different signs of the same disease. The symptoms need not all appear always in all persons suffering from the syndrome, such as will appear from the following.
[0033] A fatigue syndrome is a syndrome where fatigue is always present as a principal symptom often accompanied by other symptoms as described below.
[0034] One example of a fatigue syndrome is the Chronic Fatigue Syndrome. The term “Chronic Fatigue Syndrome” has recently been agreed upon (Journal of the Royal Society of Medicine, Volume 84, February 1991) as a standard term with a distinct meaning, but the disease has been known for many years under other names such as, epidemic neuromyasthesia, idiopathic chronic fatigue and myalgia syndrome, chronic infectious mononucleosis, benign myalgic encephalomyelitis, post-viral fatigue syndrome, fibrositis-fibromyalgia syndrome, Icelandic disease, Akureyri disease, or Royal Free Hospital disease.
[0035] According to the above-mentioned agreement, The Chronic Fatigue Syndrome is defined by the following symptom:
[0036] A fatigue which is the principal symptom, which has a definite onset, and is severe, disabling and affects both physical and mental functioning, and furthermore the fatigue should have been present for a minimum of 6 months at which it was present for more than 50% of the time and by one or more of the following symptoms which may or may not be present:
[0037] Sleep disturbances, which are changes in the duration of sleep and/or quality of sleep. The changes could be hypersomnia or increased sleep, or insomnia or reduced sleep, (which should further be described as either difficulty of getting off to sleep, early wakening, or subjectively disturbed or unrefreshening sleep). The changes of the quality of sleep is contemplated to be due to a decrease in REM sleep, e.g. the deep sleep which is necessary for a feeling of having a good and refreshening sleep.
[0038] Disability, which refers to any restriction or lack (resulting from loss of psychological or physiological function) of ability to perform an activity in the manner or within the range considered normal for human being, i.e. things that people cannot do in the areas of occupational, social and leisure activities because of their illness. The disability should be distinguished from impairment of function (e.g. weak legs) and from handicap (e.g. unable to work). Furthermore, there should be a definite and persistent change from a previous level of functioning.
[0039] Mood disturbances such as depressed mood, anhedonia, anxious mood, emotional lability and irritability, the severity of the mood disturbances should be assessed on standard scales. Furthermore it should be determined whether the disorder is sufficient to meet the diagnostic criteria for major depressive disorders.
[0040] Myalgia, which is pain or aching felt in the muscles. The myalgia should be disproportionate to exertion. It should be distinguished from feelings of weakness and pain felt in other areas such as the joints.
[0041] In the present context, the term “fatigue syndrome” designates a syndrome which, qualitatively, that is, with respect to the character of the syndrome, is substantially identical to the condition characterized in the Chronic Fatigue Syndrome, but which quantitatively, that is, with respect to the duration of the syndrome, has not yet, at the time of treatment, lasted for the 6 months which constitute a compulsory element of the definition of the Chronic Fatigue Syndrome.
[0042] Thus, if a patient shows symptoms which, had they prevailed for at least 6 months, would categorize the patient as suffering from the Chronic Fatigue Syndrome, but which have not yet, at the time in question, prevailed for 6 months, the shorter duration, although bringing th syndrome outside the establish d definition of Chronic Fatigue Syndrome, does not bring the condition outside the definition of fatigue syndrome as used herein.
[0043] With reference to the definition of the Chronic Fatigue Syndrome, the fatigue syndrome definition used herein will, thus, at l ast comprise the same disabling fatigue condition which (if it has lasted for at least 6 months) already in itself would establish a condition under the definition of the Chronic Fatigue Syndrome.
[0044] Normally, howev r, a fatigu condition will not b consider d a syndrome unless it has had a duration and/or a course which distinguishes it from, e.g., the fatigue resulting from normal exertion. Thus, fatigue syndrome in the sense of the present specification is one which is complained of, significantly affects the person's functioning, and represents a clear change from a previous state. Its duration will have been at least 14 days, normally at least one month. In the present specification and claims, a severe fatigue syndrome is defined as a fatigue syndrome the duration of which is at least 2 months, normally at least 3 months.
[0045] Another example of a fatigue syndrome is the Post-infectious Fatigue Syndrome which may be considered as a sub-class of the Chronic Fatigue Syndrome. The Post-infectious Fatigue Syndrome is defined by the same symptoms as the Chronic Fatigue Syndrome and furthermore, a definite evidence of infection at onset must have been provided and the infection should have been corroborated by laboratory evidence.
[0046] Yet another example of a fatigue syndrome is the fatigue associated with human immunodeficiency virus (HIV) infection (AIDS).
[0047] A still further fatigue syndrome is the syndrome associated with preeclampsia.
[0048] As appears from the above, the crucial feature of the present invention is the administration of a cholinesterase. Compounds which function as cholinesterase inhibitors may be divided into several groups, namely poison gases for use in warfare, insecticides, such as malathion, and drugs. In the present context, the term “pharmaceutically acceptable” indicates that the cholinesterase inhibitors in question are not such which will be poisonous, in other words, they pertain to the drug group and not to the poison group.
[0049] Pharmaceutically acceptable cholinesterase inhibitors are, e.g., galanthamine and galanthamine derivatives, norgalanthamine and norgalanthamine derivatives, epigalanthamine and galanthamine, physostigmine, tacrine and tacrine analogues, fasciculin, metrifonate, heptyl-physostigmine, norpyridostigmine, norneostigmine, and huperzine or a prodrug therefor. Some of the cholinesterase inhibitors show certain undesirable properties, such as short half life, etc. In some cases, such deficiencies can be compensated for by modifying the compound into a prodrug for the active compound, in accordance with well-known principles for prodrug construction, such as introduction of hydrophilic groups to enhance the solubility of a compound in water, thus making it possible to formulate the compound as a an injection solution, an introduction of lipophilic groups such as ester groups to enhance the capability of the compound to pass the blood-brain barrier.
[0050] The presently preferred cholinesterase inhibitor used according to the invention is galanthamine. Galanthamine is known as an acetylcholinesterase acting substantially only at nicotinic receptor sites, that is, having a high selectivity for acetylcholinesterase as opposed to butyrylcholinesterase. A more detailed discussion of galanthamine and galanthamine derivatives is given below:
[0051] Galanthamine is a well-known acetylcholinesterase inhibitor which is active substantially selectively at nicotinic receptor sites and has substantially no effect on muscarinic receptor sides, is capable of passing the blood-brain barrier in humans, and presents no severe side effects in therapeutically necessary dosages.
[0052] Galanthamine and acid addition salts thereof have, for many years, been known to have anti-cholinesterase properties.
[0053] Galanthamine, a tertiary alkaloid, has been isolated form the bulbs of the Caucasian snowdrops Galantanus woronowi (Proskurnina, N. F. and Yakoleva, A. P. 1952, Alkaloids of Galanthus woronowi. II. Isolation of a new alkaloid. (In Russian.) Zh. Obschchei Khim. (J.Gen.Chem.) 22, 1899-1902. Chem.abs. 47,6959, 1953. It has also been isolated from the common snowdrop Galanthus Nivalis (Boit, 1954).
[0054] Galanthamine has been used extensively as a curare reversal agent in anaesthetic practice in Eastern bloc countries (cf. review by Paskow, 1986) and also experimentally in the West (cf. Bretagne and Valetta, 1965: Wislicki, 1967; Conzanitis, 1971).
[0055] Pharmacokinetic studies have recently been made by Thomsen, T. and H. Kewitz. (Selective Inhibition of Human Acetylcholinesterase by Galanthamine in vitro and in vivo. Life Sciences, Vol 46, pp. 1553-1558 (1990), and, by the same authors, Galanthamine Hydrobromide in a Long-Term Treatment of Alzheimer's Disease. Dementia 1990, 1:46-51).
[0056] It is believed that the excellent and surprising effect possessed by galanthamine is due to its sp cific profile of properties, the most important of the known ones of which can be summariz d as follows:
[0057] capability to pass the blood brain barrier in humans,
[0058] a high selectivity for acetylcholinesterase as opposed to butyrylcholinesterase (about 50-fold when m asured by the in vitro method by Thomsen et al., see below),
[0059] a sufficient elimination half life to warrant duration of an effective concentration of at least 4 hours, probably at least 6 hours,
[0060] a relatively low toxicity in therapeutical concentrations,
[0061] capability of being effective in doses which are sufficiently low to k p peripheral side effects low.
[0062] Galanthamine must be considered as being a very desirable drug for the treatment according to the invention: The elimination half life of galanthamine hydrobromide is over four hours; it shows a practically complete renal elimination. A complete elimination of metabolites and galanthamine takes place in 72 hours. Galanthamine has been used in Eastern Block countries since around 1958 as an anticurare agent in anesthesiology, and a considerably number of patients have been treated with galanthamine without any reported case of liver toxicity or serious side effects. Galanthamine hydrobromide, being a tertiary amine and lipid soluble, is absorbed rapidly from the gut and transverses the blood brain barrier easily. The common side effects, other than the ones related to cholinergic crisis, are either nausea or vomiting, and a slight headache. However, these side effects are rare, especially when care is taken to start medication in low doses such as mentioned above.
[0063] The galanthamine can suitably be administered orally in the form of an acid addition salt, e.g. the hydrobromide, but other administration forms are possible and realistic, such as is described below.
[0064] Because galanthamine has substantially no effect on the activity at muscarinic receptor sites, as apparent from its high selectivity for acetylcholinesterase as opposed to butyrylcholinesterase, it will not give rise to the often severe side effects on the heart which are associated with cholinesterase inhibitors which have a low selectivity for acetylcholinesterase as opposed to butyrylcholinesterase. Galanthamine has an in vitro selectivity for acetylcholinesterase opposed the effect on butyrylcholinesterase of 50 to 1, as reported by Thomsen, Life Sciences, Vol 46, pp. 1553-1558 (1990).
[0065] As indicated above, the amount of galanthamine is preferably adjusted individually based upon observation of the effect of initially very low dosages. There is as considerable difference with respect to how sensitive individuals are to acetylcholinesterase inhibitors. Thus, the amount of galanthamine is suitably adjusted by means of a regimen starting at low dosages, e.g. 1 mg, preferably at 5 mg, per day, but, if appropriate, even as low as 0.1 mg per day, if the dosage is well tolerated by the patient within the first two hours the dosages is increased to, e.g. 10 mg per dosage dosed 3 to 4 times per day or in some severe cases to 60 mg or more per day dosed over 3 or 4 times.
[0066] Because cholinergic crisis, a life-threatening dose-dependant side effect of all kinds of acetylcholinesterase inhibitors, should, by all means, be avoided, it is recommended to start with the low dosages as mentioned above and furthermore not to exceed 150 mg per day and preferably not to exceed dosages above 60 mg per day, unless the patient shows a very low sensitivity to acetylcholinesterase inhibitor, in which case higher doses, such as 200 mg per day, could be used.
[0067] The treatment according to the invention should preferably be continued at least for two months, such as, e.g., three months, or until the syndrome has disappeared.
[0068] While galanthamine has, indeed, given remarkable results, such as appears from the clinical cases given in the examples, it is justified to presume that other acetylcholinesterase inhibitors which are functional equivalents to galanthamine with respect to its combination of high selectivity with respect to nicotinic receptor sites and capability of passing the blood brain barrier in humans in vivo, will also show a useful combination of effect against fatigue syndrome and acceptability in the clinic, although it cannot be ruled out that galanthamine, galanthamine salts and galanthamine derivatives, due to the special conformation of the galanthamine ring system, have specific properties which are decisive for the remarkable effect.
[0069] In accordance with the above, compounds which are functional equivalents of galanthamine are defined herein as compounds which
[0070] a) possess an at least 10-fold selectivity, preferably an at least 20-fold selectivity, more preferably an at least 40-fold selectivity, and most preferably an at least 50 fold selectivity, for acetylcholinesterase as opposed to butyrylcholinesterase, when measured by the in vitro method by Thomsen et al., see below,
[0071] b) are capable of passing the blood brain barrier in humans in vivo.
[0072] As will be understood from the above definition, a compound can be subjected to well-defined and relatively short-lasting tests (see below) to determine whether it fulfills criterion a) above. Then, the likelihood whether the compound will pass the blood brain barrier in humans in vivo (criterion b)) can be assessed in a model. One such model is a whole rat brain model in which rats are given the acetylcholine esterase in vivo and are then killed wh reupon homogenate of the rat brain is examined with respect to the acetylcholinesterase activity; the result is then compared to the acetylcholinesterase activity in rat brains not treated with acetylcholinesterase inhibitors. Another rat model could b the measurement and comparison of acetylcholinesterase activity in cerebrospinal fluid in vivo in the same rat before and aft r treatment. If the compound fulfills criterion a), and its likelihood of passing the blood brain barrier has been established in one of the above-described rat brain models, it will be a candidate drug. An initial determination of toxicity is necessary in cases before any effect in humans can b assessed; such initial determination of toxicity can b performed by pharmacologic t sts in a manner known per se. After th pharmacological tests, the capability of th candidate drug of passing the blood brain barrier in humans in vivo can be det rmined by the method described below. If the candidate drug has been found to possess this capability, it can be passed to the testing proper. Optionally, the candidate drug can be subjected to additional short-lasting tests, such as the in vivo selectivity test described by Thomsen et al., and a test to determine whether it increases cortisol level in humans. Both of these tests give further indication of whether the candidate drug has a spectrum of properties equivalent to galanthamine with respect to what must be presumed to be essential properties. Peripheral side effects will be assessable when the effect is tested clinically, which is acceptable from an experimental and ethical point of view, provided the toxicity has first been assessed by the above-mentioned pharmacological tests. With respect to the final assessment of the candidate drug's effect on fatigue syndrome, a rational and efficient design of the assessment will involve an initial test on one or a few patients and, provided the initial test is positive, the above-mentioned conclusive double blind test. Because of the well-defined and brief character of all of the tests, and especially the well-defined in vitro character of the initial screening, the test series for identifying useful functional equivalents of galanthamine is a reasonable an not burdensome routine which is within the realm of the person skilled in the art.
[0073] Functional equivalents and derivatives of galanthamine which are useful in the method of the invention will be employed in the same manner as stated herein for galanthamine. Whenever quantities of such a functional equivalent or derivative are referred to herein, the quantities are given as the equipotent quantity of galanthamine hydrobromide with respect to inhibition of acetylcholinesterase, that is, as the quantity of galanthamine hydrobromide which results in the same inhibition of acetylcholine esterase in the above-mentioned in vitro test according to Thomsen et al as does the functional derivative or derivative.
[0074] The selectivity of the acetylcholinesterase inhibitor for acetylcholinesterase as opposed to butyrylcholinesterase can be determined by in vitro and in vivo tests as described by Thomsen and Kewitz in the above mentioned paper Selective Inhibition of Human-Acetylcholinesterase by Galanthamine in vitro and in vivo, Life Sciences, Vol 46, pp. 1553-1558 (1990), and T. Thomsen, H. Kewitz and O. Pleul, J. Clin. Chem. Clin. Biochem. 26 469-475 (1988). The in vitro test described by Thomsen and Kewitz in Life Sciences, Vol 46, pp 1553-1558 (1990) is the one referred to above in connection with criterion a) and whenever numeric (10-fold, 20-fold, 40-fold) reference to selectivity for acetylcholinesterase as opposed to butyrylcholinesterase is made in the claims. According to Thomsen and Kewitz, galanthamine hydrobromide, when tested under the conditions described, shows a 50-fold selectivity; this selectivity value is taken as the “fixpoint” whenever in vitro selectivities are discussed herein and could be used, for the purpose of determining the selectivities for other cholinesterase inhibitors, as a calibration value which is the one to establish with galanthamine hydrobromide in any repetition of the experiment described by Thomsen and Kewitz. Thus, with reference to this determination method, a preferred acetylcholinesterase inhibitor is one which in the in vitro method described has an at least 10-fold selectivity for acetylcholinesterase as opposed to butyryicholinesterase, such as an at least 20-fold selectivity for acetylcholinesterase as opposed to butyrylcholinesterase, e.g. an at least 40-fold selectivity for acetylcholinesterase as opposed to butyrylcholinesterase.
[0075] A relatively easy commercially available selectivity test which can be used as a practical tool in the screening of candidate drugs is the test described in Example 1 herein.
[0076] The capability to pass the blood brain barrier in vivo in humans can be assessed by either by a test which could be called “Auditory brain stem response” or by a test which is based on the measurement of CRH, ACTH and cortisol. The rationale behind these tests, and the way they are performed, is explained in the following:
[0077] The auditory brain stem response test is based on the observation that manio-depressive patients are hypersensitive to cholinergic influences, one manifestation hereof being hypersensitivity to auditory signals as assessed by the increase of amplitude of auditory evoked potentials in the nuclei of the auditory system in the brain stem, i.e. on the “brain side” of the blood brain barrier. This hypersensitivity manifests itself in a lower amplitude than in normal humans when the person is not treated with a cholinergic agent such as acetylcholinesterase inhibitor; and a very significantly increase of the amplitude when the person has received a cholinergic agent, provided, of course, that th cholinergic agent is able to pass the blood brain barrier and thus enter the nuclei of the auditory system in the brain stem. See also example 3.
[0078] The other test based on the measurement of CRH (corticotropic-hormone releasing hormone released from the hypothalamus in the brain, and which releases both ACTH from the adenohypophysis and cortisol from the adrenal medulla) and ACTH (corticotropic hormone, which releases cortisol from the adrenal medulla) is carried out by measuring the CRH, ACTH and cortisol concentration in the blood in healthy persons before and after medication with acetylcholinesterase. If the concentration of all three hormone are increased after m dication or at least CRH and cortisol are increased it is proven that the ac tylcholinesterase has effect in the central nervous system, and since it is an in vivo experiment it is further proven that the acetylcholinesterase has passed the blood brain barrier.
[0079] As mentioned above, the selectivity of the acetylcholinesterase inhibitor can, as an additional characterization, optionally be expressed with reference to the in vivo determinations performed by Thomsen and Kewitz on galanthamine and described in the above-mentioned paper Selective Inhibition of Human Acetylcholinesterase by Galanthamine in vitro and in vivo, Life Sciences, Vol 46, pp. 1553-1558 (1990). With reference to this determination, a preferred acetylcholinesterase inhibitor is one which, upon administration in an amount of 10 mg to a healthy adult, results in inhibition of at least 40% of the acetylcholinesterase activity in erythrocytes from the adult within about 2-5 minutes and no substantial inhibition of butyrylcholinesterase therein, such as an acetylcholinesterase inhibitor which, when administered in an amount of 10 mg to a healthy adult, results in inhibition of at least 50% of the acetylcholinesterase activity in erythrocytes from the adult within about 2-5 minutes. For galanthamine, Thomsen and Kewitz found 65% inhibition of acetylcholinesterase in the erythrocytes within 2 minutes after administration of 10 mg of galanthamine i.v. in a healthy volunteer, whereas no inhibition of butyrylcholinesterase in plasma was seen. Also these determinations are referred to in claims herein and should, in connection with the evaluation of the corresponding selectivities of candidate drugs different from galanthamine hydrobromide be considered the “calibration fixpoints” which will be established with galanthamine hydrobromide in any repetition of this experiment.
[0080] As mentioned above, it is possible that galanthamine, galanthamine salts and galanthamine derivatives, due to the special conformation of the galanthamine ring system, have specific properties which are decisive for the remarkable effect established according to the present invention. Thus, according to one aspect of the invention, compounds which are contemplated to be valuable and useful in the treatment according to the invention are the compounds having the formula II (formula II also represent galanthamine itself)
[0081] wherein R 1 and R 2 which may be the same or different each represents a hydrogen atom or an acyl group, such as a lower alkanoyl group, e.g. an acetyl group or a straight-chained or branched alkyl group, e.g. methyl, ethyl, propyl, or isopropyl; R 3 is a straight or branched chain alkyl, alkenyl or alkaryl group which is optionally substituted by a halogen atom or a cycloalkyl, hydroxy, alkoxy, nitro, amino, aminoalkyl, acylamino, heteroaryl, heteroaryl-alkyl, aroyl, aroylalkyl or cyano group; and R 4 represents a hydrogen or halogen atom attached to at least one of the ring carbons of the tetracyclic skeleton, with the proviso that when R 4 is in a position neighbouring the nitrogen atom, then R 4 is preferably different from halogen, and salts thereof, such as a hydrobromide, hydrochloride, methylsulphate or methiodide.
[0082] In the compounds of formula I, alkyl moieties preferably contain 1 to 8 carbon atoms, halogen atoms are preferably fluorine, chlorine, or bromine, especially fluorine or chlorine, aryl moieties are preferably phenyl, cycloalkyl groups are preferably 3- to 7-membered rings, especially cyclopropyl or cyclobutyl, and heteroaryl moieties are preferably 5- to 8-membered rings, e.g., thienyl, furyl, pyridyl, pyrrolyl, or pyrizanyl.
[0083] Among the compounds of the formula I are those described in EP-A-236684. The compounds of formula I may be prepared according to conventional techniques, including those described in EP-A-236684.
[0084] A broader range of compounds which, from the point of view of structural similarity with galanthamine, ar contemplat d to be valuabl compounds useful in the method of the inv ntion are galanthamine derivatives of the general formula I
[0085] wherein the broken line represents an optionally present double bond in one or the two of the positions shown, R 1 and R 2 are each selected independently from the group consisting of hydrogen, hydroxyl, amino or alkylamino, cyano, sulfhydryl, alkoxy of 1-6 carbon atoms, alkylthio, aryloxy, arylthio, R 5 -substituted aryloxy, R 5 -substituted arylthio, aralkoxy, an aliphatic or aryl carbamyl group wherein the aliphatic or aryl moiety may be R 5 substituted or unsubstituted, aralkylthio, R 5 -substituted aralkoxy, R 5 -substituted aralkythio, aryloxymethyl, R 5 -substituted aryloxymethyl, alkanoyloxy, hydroxy-substituted alkanoyloxy, benzoyloxy, R 5 -substituted benzoyloxy, aryloxycarbonyl and R 5 -substituted aryloxycarbonyl, R 1 may also be alkyl of up to 14 carbon atoms, or hydroxymethyl, R 2 may also be carboxymethyl, provided that at least one of R 1 and R 2 is hydroxy, amino or alkylamino unless R 7 or R 8 is hydroxymethyl, R 3 is hydrogen, straight or branched chain alkyl of 1-6 carbon atoms, cycloalkylmethyl, phenyl, R 5 -substituted phenyl, alkylphenyl, R 5 -substituted alkylphenyl, heterocyclyl selected from α- or β-furyl, α- or β-thienyl, thenyl, pyridyl, pyrazinyl, and pyrimidyl, alkyl-heterocyclyl or R′-substituted heterocyclyl, where R′ is alkyl or alkoxy,
[0086] each R 4 is independently selected from hydrogen, hydroxyl, sulfhydryl, alkyl, aryl, aralkyl, alkoxy, mercaptoalkyl, aryloxy, thiaryloxy, alkaryloxy, mercaptoalkaryl, nitro, amino, N-alkylamino, N-arylamino, N-alkarylamino, fluoro, chloro, bromo, iodo, and trifluoromethyl,
[0087] R 5 is selected from the same groups as R 4 ,
[0088] R 6 is hydrogen, halo, trifluoromethyl or alkyl of 1 to 4 carbon atoms, with the proviso that when R 6 is in position 7 or 9, it is preferably not halo.
[0089] R7 is selected from the same groups as R 4 or may be hydroxyalkyl of 1-2 carbon atoms,
[0090] R 8 is hydrogen or hydroxymethyl,
[0091] R 9 is hydrogen or alkyl of 1 to 6 carbon atoms, or when R 2 is hydroxyl, R 9 may be a moiety of formula I wherein R 9 is hydrogen and R 2 is a linking bond; or
[0092] R 2 and R 9 may jointly form semicarbazone,
[0093] X is oxygen or NR 5 ,
[0094] Y is nitrogen or phosphorus,
[0095] and methylenedioxy derivatives thereof with the proviso that when X is O, R 3 is not methyl when R 1 is methoxy, R 2 is hydroxy, and all R 4 are hydrogen, or a pharmaceutically acceptable acid addition salt thereof.
[0096] Examples of subclasses and specific compounds of the formula II are given in WO 88/08708, which also discloses methods for preparing the compounds II.
[0097] Galanthamine, galanthamine salts, galanthamine derivatives and galanthamine functional equivalents, when suited therefor, may be administered orally at a dosage of e.g. 5-150 mg per day, such as 10-60 mg per day, e.g. 10-50 mg, such as 10-40 mg, per day, the dosage being adapted to the patient and the patient's response. As mentioned above, the treatment should oft n be start d with a low dosage and then increased until the suitable dosage has been established. The dosage of galanthamine functional equivalents or galanthamine derivatives is expressed as the equipotent amount of galanthamine hydrobromide, the reference basis being the capability of inhibiting acetylcholinesterase in the Thomsen et al. in vitro test mentioned above.
[0098] Examples of parenteral administration ranges are 0.1-1000 mg per day, such as 5-1000 mg per day, e.g. 10-500 mg per day, including 50-300 mg per day; low r dosages are often preferred, such as 10-50 mg per day, e.g. 10-30 mg per day.
[0099] For the oral administration, galanthamine or a galanthamine salt or derivative or a functional equival nt may be formulated, for example, as an aqueous suspension or a solution in aqueous ethanol or as a solid composition such as a tablet or capsule. Suspensions or solutions for oral administration are typically of a concentration of 1-50 mg/ml, more commonly 5-40 mg/ml, for example, 10-40 mg/ml, typically 20-30 mg/ml of galanthamine. Divided doses into the range 0.5-5 mg/kg body weight per day are useful, in some situations divided doses in the range of 0,1-3 mg/kg body weight per day may also prove useful. Examples of dosages are up to 2000 mg per day, such as 0.1-2000 mg per day, or 5-2000 mg per day. Other ranges that should be mentioned are 100-600 mg per day or 10-500 mg per day, such as 10-50 or 10-30 mg per day. Typically, one might administer a dosage of 20-100 mg per day to a patient of a body weight of 40-100 kg, although in appropriate cases such dosages may prove useful for patients having a body weight outside this range. However, in other instances dosages of 50-300 mg per day to a patient of a body weight of 40-100 kg may be also be very useful. In other cases, dosages as low as 10 mg and as high as 200 mg is may be appropriate for persons in this body weight range.
[0100] Galanthamine and its acid addition salts form crystals. They are generally only sparingly soluble in water at room temperature; therefore, injectable compositions are normally in the form of an aqueous suspension. If necessary, pharmaceutically-acceptable suspension aids may be employed. Typically, such a suspension will be employed at a concentration of 0.1-50 mg/ml, such as 1-50 mg/ml, more commonly 5-40 mg/ml, for example, 5-30 mg/ml or 10-40 mg/ml, such as 10-30 mg/ml, especially 20-30 mg/ml of galanthamine. As mentioned above, typical dosage rates when administering galanthamine by injection are the range 0.01-20 mg per day depending upon the patient. For example, divided doses in the range 0,5-5 mg/kg body weight per day may prove useful. Typically, one might administer a dosage of 5-50 mg per day to a patient of a body weight of 40-100 kg, although in appropriate cases such dosages may prove useful for patients having a body weight outside this range. In other cases, dosages as low as 5 mg and as high as 200 mg per day may be appropriate for persons in this body weight range.
[0101] Galanthamine and its pharmaceutically acceptable acid addition salts, and its derivatives and functional equivalents, when suited therefor, may be administered by subcutaneous, intravenous or intramuscular injection.
[0102] The parenteral dosage rate of galanthamine can also be expressed by reference to the body weight of the patient; in this case, a normal dosage rate will often be 0.1 to 4 mg/kg body weight. Depot compositions will often deliver a dosage rate of 0.01 to 5.0 mg/kg per day.
[0103] In preparing tablets or capsules, standard tablet or capsule-making techniques may be employed. If desired, a pharmaceutically acceptable carrier such as starch or lactose may be used in preparing galanthamine or galanthamine equivalent tablets. Capsules may be prepared using soft gelatine as the encapsulating agent. If desired, such capsules may be in the form of sustained release capsules wherein the main capsule contains microcapsules of galanthamine or functional equivalents thereof which release the contents over a period of several hours thereby maintaining a constant level of galanthamine or its functional equivalent in the patient's blood.
[0104] The following specific formulations may find use according to the invention: Tablets or capsules containing 0.1, 1, 2, 5, 10 and 25 mg galanthamine hydrobromide or functional equivalent to be taken four times a day, or a sustained-release preparation delivering an equivalent daily dose.
[0105] Liquid formulation for oral administration available in 5 mg/ml and 25 mg/ml concentration.
[0106] Other interesting administration forms of galanthamine and functional equivalents are suppositories, a slow-release plaster, and other depot compositions.
[0107] All of the above-mentioned administration forms are prepared in manners known per se.
[0108] Although galanthamine must be considered as having a high degree of safety, there have been certain side effects in a few of the patients treated. These have been slight nausea in about 30% of the cases (the nausea, however, disappearing after about one week of treatment), vomiting and dizziness in 5-10% of the patients (also disappearing after about one week of treatment in most cases), and more severe side effects in 4-6% of the patients. These more severe side effects must be considered acceptable in view of the effect of the drug; however, in patients who are suspected of developing arrhythmia, it should be considered to administer, e.g., atropine in combination with the treatment according to the invention.
[0109] Th administration forms for th cholinesterase inhibitors, galanthamine, the galanthamine salts and the galanthamine derivatives may be orally and parenterally. The administration being dependent on the patient's age and weight, and on the daily life of the patient as well as the severity of the disease.
[0110] Parenteral administration may comprise suitable injection, e.g. intravenous, intramuscular, subcutaneous, as well as transdermal or r ctally administration or implantation of e.g. suitable d livery devices, such as a intrathetical devic .
[0111] Formulations for parenteral use may b a solution or suspension, a plaster for transdermal application, or a suppository.
EXAMPLE 1
[0112] Test for cholinesterase activity in blood samples
[0113] Method
[0114] SIGMA DIAGNOSTICS® CHOLINESTERASE (PTC) kit, available from Sigma Diagnostics, can be used for determining the activity and selectivity of cholinesterase inhibitors. In the following, it is illustrated how the kit is used for the determination of the activity and selectivity of Nivalin (Galanthamine hydrobromide).
[0115] Reactions involved in the cholinesterase assay are as follows:
[0116] 5-Thio-2-Nitrobenzoic Acid is assessed by measuring the absorbance at 405 nm. The rate of change in absorbance at 405 nm is directly proportional to cholinesterase activity.
[0117] The activity of erythrocyte cholinesterase may be calculated on the basis of the measurement of butyrylcholinesterase (pseudocholinesterase) in serum and cholinesterase in hemolyzed whole blood (hemolysate), both measured simultaneously by the method described above, and evaluated according to the hematocrit value according to the formula
HChE =( EChE×Hct* )+( PChE ×(1- Hct* ))
[0118] [0118] EChE = HChE - ( PChE × ( 1 - Hct *) ) Hct *
[0119] *Hematocrit value expressed as decimal equivalent (i.e., 44%=0.44.
[0120] In the above formulae, EChE is erythrocyte cholinesterase activity, PChE is plasma cholinesterase activity, HChE is hemolysate cholinesterase activity, and Hct is hematocrit value of the sample.
[0121] Another way of assessing the cholinesterase activity is to measure the plasma cholinesterase and the cholinesterase in purified hemolyzed erythrocytes. By doing this, the values are obtained directly.
[0122] Blood samples from 3 patients were tested with the Sigma test. The tests were carried out with samples where no Nivalin was added and with samples where 1.25 μg/ml Nivalin and 2.5 μg/ml were added in vitro. The results are shown below in table 1.1.
TABLE 1.1 Nivalin added μg/ml Hemolysate ChE activity Serum ChE activity 0 1.00 1.00 1.25 0.96 0.98 2.50 0.86 0.97
[0123] The results show a significant reduction of the hemolysate cholinesterase activity with increased concentration of galanthamine hydrobromide, whereas the data for the serum activity do not show any statistically significant change as a response to the addition of the galanthamine hydrobromide, which is an indication of a high selectivity of the galanthamine hydrobromide with respect to acetylcholinesterase as opposed to butyrylcholinesterase. Selectivity for acetylcholinesterase in erythrocytes opposed to butyrylcholinesterase is contemplated to reflect the selectivity for acetylcholinesterase at nicotinic receptor sites opposed to the acetylcholinesterase at muscarinic receptor sites.
[0124] This test may be used as a screening for candidate cholinesterase inhibitors with respect to their selectivity.
EXAMPLE 2
[0125] Formulations of tablets containing galanthamine
Composition of 1 tablet containing 1 mg galanthamine Galanthamine hydrobromide 0.001 g Calcium phosphate 0.032 g Lactose 0.005 g Wheat Starch 0.0056 g Microcrystalline Cellulose 0.015 g Talc 0.0007 g Magnesium Stearate 0.0007 g Composition of 1 tablet containing 5 mg galanthamine Galanthamine hydrobromide 0.005 g Calcium phosphate 0.024 g Lactose 0.004 g Wheat Starch 0.004 g Microcrystalline Cellulose 0.04 g Talc 0.002 g Magnesium Stearate 0.001 g Composition of 1 tablet containing 10 mg galanthamine Galanthamine hydrobromide 0.010 g Lactose 0.040 g Wheat Starch 0.0234 g Microcrystalline Cellulose 0.0374 g Talc 0.0036 g Magnesium Stearate 0.0012 g Gelatin 0.0044 g
[0126] Preparation
[0127] All th tablets ar prepared according to routine tabletting procedures.
EXAMPLE 3
[0128] Diagnostic criteria for patients with the Chronic Fatigue Syndrome (CFS)
[0129] To diagnose Chronic Fatigue Syndrome a guideline for research has been published (5).
[0130] A syndrome characterized by fatigue as the principal syndrome.
[0131] A syndrome of definite onset that is not life long.
[0132] The fatigue is severe, disabling and affects physical and mental functioning.
[0133] The symptom of fatigue should have been present for a minimum of 6 months during which it was present for more than 50% of the time.
[0134] Other symptoms may be present, particularly myalgia, mood and sleep disturbances.
[0135] Certain patients should be excluded from the definition. They include:
[0136] Patients with established medical conditions known to produce chronic fatigue (eg. severe anemia). Such patients should be excluded irrespective of whether the medical condition is diagnosed at presentation or only subsequently. All patients should have a history and physical examination performed by a competent physician.
[0137] Patients with current diagnoses of schizophrenia, manic depressive illness, substance abuse, eating disorder, or proven organic brain disease. Other psychiatric disorders (including depressive illness, anxiety disorders, and hyperventilation syndrome) are not necessarily reasons for exclusion.
EXAMPLE 4
[0138] Diagnostic criteria for patients with the Post-infectious Fatigue Syndrome (PIFS)
[0139] The patients must fulfill the criteria for CFS as defined above and should also fulfill the following criteria:
[0140] A definite evidence of infection at onset or presentation
[0141] The syndrome is present for at least 6 months after onset of the infection.
[0142] The infection has been corroborated by laboratory evidence.
EXAMPLE 5
[0143] Double-blind cross-over trial of the effect of galanthamine on Chronic Fatigue Syndrome (CFS) Persons
[0144] 20 persons suffering from Chronic Fatigue Syndrome fulfilling the criteria described in example 4 or 5.
[0145] Method
[0146] Each patient received treatment for a minimum of 8 weeks. The first 2 weeks incorporated an escalating schedule to stabilise the patient on an appropriate dose. The trial was running for eight weeks.
[0147] 11 of the persons were randomly allocated to galanthamine treatment, and the remaining 9 to placebo treatment. The protocol for the trial made provisions for the clinician to opt after two weeks of treatment for transfer to the alternative treatment. The switch to the alternative treatment was made if he regarded the patient as having failed to benefit from the 2 weeks therapy.
[0148] The data available for the evaluation covered groups of patient-completed visual analogue scales to assess sleep disturbance, fatigue, myalgia, work capacity/satisfaction, and dizziness, together with time per response on a visual search task.
[0149] Results
[0150] The results of th analysis of data from the visual analogue scales during the first two weeks of treatment ar shown in table 6.1.
[0151] In order to assess any underlying, overall p rformance difference between the galanthamine and placebo treat d patients, the median (th statistic which differentiates the upper and lower 50% of scores) of the changes across all scales, was computed for the placebo treated patients.
[0152] Using this median as an ind x of averag “placebo response”, it was found that 68.18% of galanthamine treated patients changes on the analogue scales fall above the placebo median, a differ nce (from the top 50% of placebo treated patients) which is statistically significant (exact p=0.033). This demonstrates an underlying trend for CFS patients treated with galanthamine to generate more beneficial changes on these visual analogue scales, which cannot be explained as a ‘placebo response’.
[0153] Turning from the patients' own evaluation of therapeutic benefit, to the clinicians' assessment of response during the first two weeks of treatment, it was found that at this point all 9 of the patients randomly allocated to the placebo were transferred to galanthamine, whilst only 1 of the 11 patients receiving galanthamine was transferred to placebo treatment. Such a difference (ie. 9/9 vs 1/11) is highly significant (exact p=0.00006). It is worth noting that the one patient transferred from galanthamine to placebo, after 2 weeks on placebo was found to have failed to respond and was returned to galanthamine.
TABLE 6.1 MEANS (STANDARD ERRORS) OF VISUAL ANALOGUE SCALES Scale Treatment (N) Baseline After 1 Week After 2 Weeks Sleep Disturbance Galanthamine (11) 20.78 (2.13) 17.90 (2.25) 18.42 (2.09) Placebo (9) 22.96 (1.34) 19.51 (2.44) 18.22 (2.96) Fatigue Galanthamine (11) 29.41 (1.64) 29.76 (1.70) 25.21 (2.32) Placebo (9) 28.52 (1.97) 27.67 (2.26) 26.53 (1.77) Myalgia Galanthamine (11) 17.58 (0.74) 15.95 (0.73) 13.58 (1.26) Placebo (9) 17.26 (0.71) 16.03 (1.02) 14.69 (0.95) Work Capacity/Satisfaction Galanthamine (11) 9.43 (1.17) 11.61 (1.28) 9.64 (1.61) Placebo (9) 11.29 (0.99) 10.80 (1.36) 9.43 (1.21) Memory Galanthamine (11) 5.31 (0.93) 5.89 (0.90) 5.62 (0.90) Placebo (9) 6.64 (0.75) 5.66 (0.81) 5.02 (0.81) Dizziness Galanthamine (11) 9.05 (1.26) 9.60 (1.79) 8.79 (1.81) Placebo (9) 6.47 (1.61) 6.94 (1.78) 7.52 (2.01)
[0154] The changes on the visual analogue scales of all galanthamine treated patients during treatment has been assessed, both those patients randomly allocated to galanthamine and those transferred from placebo, during the total eight weeks of the trial. These data are presented in Table 6.2.
TABLE 6.2 MEANS (STANDARD ERRORS) OF GALANTHAMINE TREATED PATIENTS ON VISUAL ANALOGUE SCALES Scale Baseline N = 19 1 Week N = 19 2 Weeks N = 19 4 Weeks N = 18 8 Weeks N = 17 Sleep 19.45 (1.83) 17.26 (1.68) 15.51 (1.91) 11.89 (1.95) 10.88 (1.93) Fatigue 28.00 (1.28) 26.63 (1.77) 20.64 (2.09) 17.42 (2.15) 17.81 (2.21) Myalgia 16.32 (0.69) 14.25 (0.89) 11.24 (1.12) 12.01 (1.15) 10.51 (0.98) Work 9.21 (0.83) 10.22 (1.07) 8.21 (1.17) 7.40 (1.25) 7.34 (1.12) Memory 5.10 (0.64) 5.41 (0.61) 4.79 (0.59) 4.33 (0.70) 4.50 (0.68) Dizziness 8.39 (1.18) 8.96 (1.40) 6.94 (1.40) 6.30 (1.32) 4.77 (1.23)
[0155] Statistically significant changes during treatment are observed on the scales assessing sleep disturbance (p<0.001), fatigue (0.001), myalgia (p<0.001), work capacity/satisfaction (p<0.001), and dizziness (p<0.001).
[0156] Comparable data to those above on the average time per response on a visual search task are as follows in Table 6.3:
TABLE 6.3 Baseline N = 19 1 Week N = 19 2 Weeks N = 18 4 Weeks N = 18 8 Weeks N = 17 6.79 (0.36) 6.24 (0.40) 5.51 (0.43) 5.83 (0.40) 5.25 (0.31)
[0157] Statistical analysis demonstrates that changes during treatment on this variable are significant (F=4.356; 4/60, p<0.001).
[0158] Data from the Cognitive Failures Questionnaire are available for all galanthamine treated patients at baseline and after 6 and 8 weeks of treatment. These are presented in Table 6.4:
TABLE 6.4 Baseline N = 19 4 Weeks N = 17 8 Weeks N = 17 47.74 (3.56) 40.94 (3.87) 38.47 (3.71)
[0159] Statistical analysis demonstrates that changes during treatment on this variable are significant (F=5.339; 2/30, p<0.001).
[0160] CONCLUSIONS
[0161] The present data appear to provide clear and consistent evidence in favour of the therapeutic efficacy of galanthamine in the treatment of CFS. This evidence is derived from an interpretation of the patients' overall self-evaluation of the beneficial effects of treatment, and form the fact that an experienced, “blind” clinician transferred all placebo patients to active treatment after only two weeks of treatment, and made a comparable switch to placebo treatment in only one patient receiving galanthamine. Additional evidence of the beneficial effects of galanthamine comes form the observed significant improvements on a visual search task (a well validated test of concentration and attention), and similar improvements on a questionnaire designed to evaluate cognitive failures.
EXAMPLE 6
[0162] Auditory brain stem r spons
[0163] Methods
[0164] Electrical potentials caused by click-stimulation in the ears ar measured with electrodes positioned outside on the head of the examin d parson. In th configuration of th potentials are components from th brain stem and the brain.
[0165] Persons
[0166] A patient suffering from bipolar manio-depression in the depressive state and a healthy person, respectively.
[0167] Drug
[0168] Tablet containing 10 mg galanthamine
[0169] Results
[0170] [0170]FIGS. 1A, 1B, 2 A and 2 B show the potentials from a depressive patient and a healthy person, both treated and untreated.
[0171] [0171]FIGS. 1A, and 2 A show that in the depressed patient, the auditory brain stem response without treatment has a much smaller, almost half, amplitude of the potential compared to the amplitude of the untreated healthy person.
[0172] Furthermore, FIGS. 1A and 1B show a dramatically increase of the amplitude in the treated depressive patient compared to untreated persons.
[0173] Also, from FIGS. 2A and 2B it is seen that the potentials do not change from the untreated person to the treated person.
[0174] Conclusion.
[0175] From the results in the depressed person it is seen that the potentials change after treatment with galanthamine, such as explained above. This means that galanthamine must be able to cross the blood-brain barrier, since it is possible to inhibit in synapsis in the brain stem, which is positioned on the “brain side” of the blood-brain barrier.
LEGENDS TO FIGURES
[0176] [0176]FIG. 1 A shows the auditory evoked response of a depressed patient (a manio depressed patient in the depressed state) without treatment with galanthamine.
[0177] [0177]FIG. 1 B shows the auditory evoked response of a depressed patient (the same as in FIG. 1 A) 2 hours after treatment with 10 mg of galanthamine.
[0178] [0178]FIG. 2 A shows the auditory evoked response of a healthy person without treatment with galanthamine.
[0179] [0179]FIG. 2 B shows the auditory evoked response of a healthy person (the same as in FIG. 2 A) 2 hours after treatment with 10 mg of galanthamine. | The invention describes novel methods for treating and preventing dementia caused by vascular diseases; dementia associated with Parkinson's disease; Lewy Body dementia; AIDS dementia; mild cognitive impairments; age-associated memory impairments; cognitive impairments and/or dementia associated with neurologic and/or psychiatric conditions, including epilepsy, brain tumors, brain lesions, multiple sclerosis, Down's syndrome, Rett's syndrome, progressive supranuclear palsy, frontal lobe syndrome, and schizophrenia and related psychiatric disorders; cognitive impairments caused by traumatic brain injury, post coronary artery by-pass graft surgery, electroconvulsive shock therapy, and chemotherapy, administering a therapeutically effective amount of at least one of the cholinesterase inhibitor compounds described herein. The invention also describes novel methods for treating and preventing delirium, Tourette's syndrome, myasthenia gravis, attention deficit hyperactivity disorder, autism, dyslexia, mania, depression, apathy, and myopathy associated with diabetes by administering a therapeutically effective amount of at least one of the cholinesterase inhibitor compounds described herein. The invention also describes novel methods for delaying the onset of Alzheimer's disease, for enhancing cognitive functions, for treating and preventing sleep apnea, for alleviating tobacco withdrawal syndrome, and for treating the dysfunctions of Huntington's Disease by administering a therapeutically effective amount of at least one of the cholinesterase inhibitor compounds described herein. A preferred cholinesterase inhibitor for use in the methods of the invention is donepezil hydrochloride or ARICEPT®. The invention also provides orally administrable liquid dosage formulations comprising cholinesterase inhibitor compounds, such as ARICEPT®. | 0 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. application Ser. No. 11/268,823, filed Nov. 8, 2005, which is a continuation of U.S. application Ser. No. 10/074,740, filed Feb. 12, 2002, now U.S. Pat. No. 6,979,343 B2, issued Dec. 27, 2005, the contents of each of which are hereby incorporated herein by reference. This application claims priority, under 35 U.S.C. §119(e) (1), of provisional application Ser. No. 60/268,773, filed Feb. 14, 2001.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates generally to the field of medical catheters. More specifically, the present invention relates to recovery catheters used in distal embolic protection.
[0004] 2. Description of the Related Art
[0005] Medical catheters are commonly employed for use in a lumen of a patient's body. The catheter enters the patient's body at an access site and is advanced through the lumen to a treatment site. The lumen may be in the patient's vascular system, such as that in a blood vessel, and the treatment site may be a stenosed region where a portion of the lumen is narrowed due to build-up of material on the lumen wall. Such narrowing is known as a stenosis.
[0006] The catheter may be guided to the treatment site through utilization of a guidewire. The guidewire typically is an elongated member having a distal end and a proximal end. The guidewire enters the patient's body at the access site and is advanced through the lumen to the treatment site. The distal end of the guidewire is the end nearest the treatment site, whereas the proximal end is the end nearest the access site. The guidewire may be positioned in proximity to the treatment site such that the distal end of the guidewire is moved to the proximal side of the treatment site (i.e., the side of the treatment site nearest the access site). The distal end of the guidewire may then cross the treatment site, thereby positioning the distal end of the guidewire on the distal side of the treatment site (i.e., the side of the treatment site farthest from the access site).
[0007] Generally, catheters comprise an elongated tubular body having a central lumen in which a guidewire can be received. The catheter is advanced along the guidewire for positioning at the treatment site. The catheter has a distal end that is advanced through the lumen of the patient's body to the treatment site.
[0008] The catheter body may have a diameter that makes it particularly difficult to advance the catheter across the treatment site if a stenosis has significantly narrowed the lumen. The prior art addresses this problem by providing a distal tip of the catheter which is tapered radially inwardly in the distal direction. Such a tapered distal tip allows for the catheter to be advanced through a narrowed portion of the lumen.
[0009] Another problem that may occur is that the catheter can become caught on a stent. A stent, generally, is a tubular wire structure that is positioned within a stenosis to maintain the lumen diameter. When a catheter is advanced across an area having a stent, the distal tip may engage an edge of the stent which can prevent further advancement of the catheter. Catheter advancement past a stent can be especially problematic when the stent is implanted in a curved vessel, or when the stent is underexpanded or incompletely deployed. This problem has been addressed by the prior art by rounding the distal tip or tapering the distal tip down to the approximate outer diameter of the guidewire in order to minimize the surface area available for engagement of the stent. This approach also provides for a gradual transition from the wire diameter to the catheter outer diameter, and tends to center the catheter in relation to the stent to facilitate stent crossing.
[0010] Some devices, such as embolic protection devices, may have a host wire that acts as a guidewire for other devices including catheters. An embolic protection device is a collapsible/expandable filter affixed to the distal portion of a guidewire. In the collapsed state, the embolic protection device is compressed toward the guidewire to give the device a smaller diameter so that it can be advanced within the lumen. In the expanded state the embolic protection device deploys outwardly from the guidewire such that it engages the wall of the lumen and acts as a filter by allowing fluid, such as blood, to pass therethrough while preventing emboli or particulate matter entrained in the fluid from passing therethrough. Emboli or particulate matter may become entrained in the fluid when a stenosis is being treated. Such particles of the stenosis may become dislodged due to contact with a treatment apparatus. Such treatments may include ablation procedures such as thrombectomy and atherectomy procedures, balloon angioplasty, stenting, and the like.
[0011] After treatment, the embolic protection device is typically collapsed in a manner wherein it maintains the captured emboli as the device is removed from the lumen. To prevent the release of the emboli back into the fluid, it is preferred to enclose the embolic protection device within a catheter. The collapsed embolic protection device has a proximal periphery that is greater than that of the outer diameter of the guidewire. Prior art catheters for receiving an embolic protection device have a relatively large diameter so as to receive the captured emboli containing protection device. Such catheters can be difficult to advance through a narrowed portion of a vessel or may become caught on a stent. If such catheters are provided with tapered tips, as described above, it becomes difficult to receive an emboli filled protection device within the catheter due to the small diameter of the tapered catheter tip. Alternatively, if prior art catheters are made small in diameter to facilitate stent crossing, it is possible that captured embolic material will be extruded through the distalmost part of the protection device filter during withdrawal of the emboli filled protection device into the small diameter catheter.
[0012] It would be advantageous to provide a catheter having a distal tip that allows passage of the catheter through a narrowed or stented portion of a lumen, while being able to receive an embolic protection device therein.
SUMMARY OF THE INVENTION
[0013] The present invention is an improved catheter for use in recovery of an embolic protection device. It is intended for use in a lumen of a patient's body such as a blood vessel. A distal tip of the catheter permits facile advance through a narrowed portion of the blood vessel, such as a stenosed region, and can conform in a manner to receive, for example, an embolic protection device having a diameter greater than the inner diameter of the distal tip.
[0014] An object of the invention is to provide a catheter that can cross stents or poorly deployed stents and yet can conform in a manner to receive an embolic protection device having a diameter greater than the inner diameter of the distal tip.
[0015] Another object of the invention is to provide a catheter that can cross stents or poorly deployed stents and yet can receive an embolic protection device without causing extruded emboli.
[0016] Yet another object of the invention is to provide a catheter with a large volume capacity that can cross stents or poorly deployed stents.
[0017] Yet another object of the invention is to provide a catheter tip that expands radially while receiving an embolic protection device having a diameter greater than the inner diameter of the distal tip.
[0018] The current invention comprises a tubular member having an inner diameter positionable over a guidewire having a device, such as an embolic protection device, carried proximate the distal end thereof. The distal tip is formed of a compliant material and has an inner diameter less than the diameter of a deployed embolic protection device. The material adapts to conformingly receive the protection device therein as the device is drawn into a lumen in the distal tip.
[0019] A preferred embodiment of the present invention comprises a distal tip attached to a main catheter body. The distal tip is defined by a body having a taper decreasing in a direction toward the distal end. The tubular body defines a wall forming a lumen therein. At the distal end, the wall of the body curves inward toward the lumen, thus forming a rolled tip. The distal tip is made of a compliant material that adapts to conformingly receive a device such as an embolic protection device.
DESCRIPTION OF THE DRAWING FIGURES
[0020] FIG. 1 is a side sectional view of a distal tip in accordance with the present invention mounted to the distal end of a catheter;
[0021] FIG. 2 is a view, similar to FIG. 1 , illustrating an alternative embodiment;
[0022] FIG. 3 is a view of the present invention illustrating a distal protection device beginning to be drawn therewithin;
[0023] FIG. 4 is a view similar to FIG. 3 illustrating the protection device being drawn into the distal tip and deforming the distal end thereof;
[0024] FIG. 5 is a view similar to FIGS. 3 and 4 illustrating the distal tip having captured the protection device.
DETAILED DESCRIPTION OF THE INVENTION
[0025] The device shown in FIG. 1 is suitable for use on a medical recovery catheter. The distal tip 10 comprises a tapered member. The member has a wall 34 that defines a lumen 30 . The lumen 30 extends through the length of the distal tip 10 . The lumen 30 extends from the proximal end 20 of the distal tip 10 to the distal end 24 of the distal tip 10 to form an aperture through the distal tip 10 . The distal end 24 is the end located farthest from the attachment to the main catheter body 40 , and the proximal end 20 is the end located nearest the catheter body 40 .
[0026] A catheter body 40 , suitable for use with the present invention, is a tubular member that has a lumen therethrough. The catheter lumen is in communication with the lumen 30 of the distal tip 10 . The catheter lumen 42 is in communication with the lumen 30 of the distal tip 10 when the distal end 44 of the catheter is connected to the proximal end 20 of the distal tip 10 . The catheter body may optionally contain a radiopaque marker band 50 in the general vicinity of the distal end 44 of the catheter. The radiopaque marker band may be entirely within the catheter body 40 , entirely within the proximal portion of the distal tip, or any combination thereof.
[0027] The wall 34 of the distal tip 10 has a given thickness. The wall thickness can be uniform or be tapered. In one embodiment, the wall 34 has a taper decreasing to a lesser thickness as the wall progresses in the distal direction as shown in FIG. 2 .
[0028] The lumen 30 of the distal tip 10 can have a uniform diameter along the length of the distal tip 10 or it may be tapered. In one embodiment, the lumen of the distal tip 30 tapers narrowingly in the distal direction. Thus, the lumen diameter can decrease as it progresses in the distal direction.
[0029] The distal end 24 of the distal tip 10 can have a rolled tip as at 32 . The portion of the wall 34 at the distal end 24 of the distal tip 10 can be rolled inward toward the axis 52 of the lumen 30 to form the rolled tip 32 .
[0030] The wall 34 of distal tip 10 has an inside surface 36 and an outer surface 38 . At the rolled tip 32 , end 22 is shown as facing inwardly toward the lumen 30 . The end 22 is facing generally radially inwardly. The outer surface 38 , over most of the length of the distal tip 10 , faces generally radially outwardly. However, at the rolled tip 32 , the outer surface 38 is curved so as to face in the distal direction to define a distal contact surface 26 .
[0031] The present invention can be used in the lumen of a human body, such as in a blood vessel 54 . The rolled tip 32 is especially designed for crossing a stented or otherwise constricted region of a blood vessel 54 . A stent is a generally tubular member having a wire wall defining the boundary of the blood vessel lumen. The catheter must pass through the lumen defined within the stent in order to cross the stented region. As a catheter in accordance with the prior art is advanced within the blood vessel, the distal end of the catheter can become caught against an axial end of the stent. This is particularly true at a curve in the blood vessel 54 , or when the stent is underexpanded or incompletely deployed. More specifically, the end of the catheter may engage an axial end of the stent. This can prevent the catheter from being able to advance farther into the blood vessel 54 . Similar problems may occur in a constricted or stenosed region of a blood vessel.
[0032] The rolled tip configuration in accordance with the present invention can prevent such problems. A catheter utilizing the distal tip 10 , having a rolled tip 32 described herein, is inserted into a blood vessel. The distal tip 10 is advanced to a stented region of the blood vessel. The rolled tip 10 is curved, as previously discussed, such that the outer portion of the wall 34 at the rolled tip 32 defines contact surface 26 . As the distal tip 10 is advanced through the region, the contact surface 26 of the rolled tip 32 may engage a stent. The rolled tip 32 prevents the distal tip 10 from becoming impassibly engaged with the stent. As the distal tip 10 is urged across the stented region, the rolled tip 32 may contact the stent, but it will deflect from the point of contact and be urged away from the stent. Thus, where the outer surface 38 contacts the stent, the distal tip 10 can continue advancing past the stent as a result of non-engagement with the axial end of the stent and allowing the distal tip 10 to continue advancing within the blood vessel 54 .
[0033] The distal tip 10 can also function to capture, for example, a protection device 58 within the lumen 30 . Lumen 30 is of a given diameter. The distal tip 10 is connected to a catheter such that the distal tip lumen 30 is in smooth communication with a catheter lumen 42 .
[0034] A device 58 to be captured within the lumen 30 might be, for example, an embolic protection device. A guidewire extends proximal with respect to the protection device 58 , extending through the lumen 30 of the distal tip 10 and catheter 40 . The device is typically positioned distal to the distal tip 10 and is secured to the guidewire. The protection device 58 has a diameter that is typically greater than that of the distal tip distal end 24 .
[0035] Again, the distal tip 10 is made of a compliant material such that the protection device 58 can be facilely received into the distal tip lumen 30 . As the protection device 58 is drawn toward the distal tip 10 , it will first contact the rolled tip 32 at the contact surface 26 . The rolled tip 32 may be urged elastically inward as the device enters the lumen 30 ( FIG. 3 ). After the device 58 has been fully drawn in the proximal direction relative to distal tip 10 , the rolled tip 32 reaches a point where it ceases to be engaged by the device, and it will return to its undeflected configuration ( FIG. 5 ). As the device 58 is being drawn into the lumen 30 , however, the lumen 30 will adapt to conformingly hold the device 58 therein and rolled tip 32 will expand radially to accommodate the periphery of the device ( FIG. 4 ). The device 58 will eventually have become fully housed within the catheter lumen, and the distal tip 10 returns, as discussed above, substantially to its original configuration.
[0036] It will be understood that resilient material forming the distal tip 10 prevents the escape of emboli when the embolic protection device 58 is captured. At least a portion of the wall of the distal tip 10 closely encompasses the periphery of the protection device 58 and assumes the shape of the periphery. As a result, emboli are prevented from passing between the periphery of the protection device 58 and the wall of the distal tip 10 . Emboli within the protection device 58 are prevented from being released back into the blood vessel. Once the protection device 58 has been received within the catheter lumen, the distal tip 10 resumes substantially the size, shape, and dimensions of its original configuration.
[0037] The distal tip 10 is a soft, deformable tip made of an elastic, compliant material. Suitable materials for making the distal tip include thermoplastic polymer and polymer blends or thermoset polymers such as silicone or silicone blends with a low durometer. One such material is a 35/40 D Pebax blend. Any other appropriate compliant materials may, however, be used.
[0038] The polymer tip may be filled with radiopaque materials such as barium sulphate, bismuth subcarbonate, tungsten powder, and the like. The tip 10 can be molded or formed using a heated die or in any other such method. Radiofrequency induction heating, electrical resistance heating, conduction heating, or any other method may be used. The preferred dimensions of the formed tip 10 will, of course, depend on the dimensions of the catheter. For example, a range of catheter sizes is from 4.2 F to 6.0 F, with corresponding inner diameters of 0.042 inches and 0.062 inches, respectively. These catheters might have distal tips with rolled distal inner diameter's of 0.025 to 0.050 inches, respectively. The diameter of the distal tip lumen 30 can be constant or tapered toward the distal end. The tip 10 may be attached to the catheter by any appropriate method such as a unitary design, heating, adhesive bonding, or molding.
[0039] It will be understood that this disclosure, in many respects, is only illustrative. Changes may be made in details, particularly in matters of shape, size, material, and arrangement of parts without exceeding the scope of the invention. Accordingly, the scope of the invention is as defined in the language of the appended claims. | A distal tip for use with a medical catheter. The tip includes a member having a wall which defines a lumen therewithin. The wall has a portion at a distal end thereof, the portion curving inwardly toward an axis of the lumen. The lumen is provided with a diameter adaptable to accommodate a device to be recovered therewithin. | 0 |
FIELD OF THE INVENTION
[0001] The field of the invention is cleaning, rinsing, and drying a microelectronic workpiece. More specifically, the field of the invention relates to methods and devices that use vapor-phase processes to clean contaminants from the surface of a microelectronic workpiece, and liquid-phase treatment to rinse and the workpiece. A microelectronic workpiece is defined here to include a workpiece formed from a substrate on which microelectronic circuits or components, data storage elements or layers, or micro-mechanical or optical elements are formed.
BACKGROUND OF THE INVENTION
[0002] During the processing of microelectronic workpieces into e.g., electronic devices such as integrated circuits, it is necessary to clean, rinse, and dry the workpieces. The cleaning process can involve the stripping of photoresist or contaminants that remain on the surface of the workpiece. In some cleaning processes, a vapor-phase is used to clean the workpiece. The vapor-phase typically includes ozone, O 3 , which is introduced into a process vessel or chamber. The O 3 can be injected into the process vessel as a dry gas, or alternatively, the O 3 can be bubbled through water to produce a moist vapor. The O 3 that is introduced into the process vessel chemically reacts with photoresist and contaminants on the surface of the workpiece.
[0003] The cleaning process removes, to the greatest extent possible, residual chemicals such as photoresist, particulate matter, organic species and contaminants that adhere to the surface of the workpiece. Chemical residue and contaminants that are not removed during the cleaning and drying steps reduce the overall yield of the manufacturing process. This reduces the number of usable electronic components, such as integrated circuits, microprocessors, memory devices, etc. that can be obtained from a workpiece.
[0004] To reduce the contamination, various surface tension effect cleaning and drying techniques have been used. Two of the most widely used technologies include thermocapillary and solutocapillary techniques. An example of a thermocapillary technique is disclosed in U.S. Pat. No. 4,722,752 (Steck). Steck teaches that the use of warm or hot water, with the subsequent reduction in surface tension, can aid in the drying of a semiconductor wafer through a combination of evaporation and low surface tension.
[0005] U.S. Pat. Nos. 4,911,761 (McConnell et al.), 5,271,774 (Leenaars et al.), 5,807,439 (Akatsu et al.), 5,571,337 (Mohindra et al.), and European Patent Specification No. 0 385 536 B1 (Lenarrs et al.) describe solutocapillary techniques.
[0006] These solutocapillary techniques typically clean and dry semiconductor wafers by introducing an organic solvent such as isopropyl alcohol (IPA) on the surface of a liquid such as deionized water. In some applications, the layer of solvent is then allowed to recede over the semiconductor wafers. In other applications, the semiconductor wafers are lifted out of the water bath. In either case, the organic solvent creates a displacement of the water on the liquid surface, effectively diluting the water near the surface. This reduces the surface tension of the surface region, causing displacement of water on the wafer surface by the organic solvent. The reduced surface tension located adjacent to the face of the semiconductor wafer promotes the removal of water and contaminants from the work piece.
[0007] Currently, vapor-phase cleaning process and the liquid-phase rinsing and drying processes are carried out in separate processing vessels. Workpieces are cleaned with the vapor-phase process in a first vessel or chamber. They are transferred to a second vessel for completion with the rinsing and drying steps. Since the cleaning and rinsing processes are performed in two separate pieces of equipment, more floor space is required for the overall process. It is desirable, however, to reduce the overall floor space needed to process microelectronic workpieces, due to the high cost required to house, maintain, and operate a semiconductor manufacturing facility under extremely clean conditions.
[0008] Accordingly, there is a need for an apparatus and method that combines the vapor-phase cleaning process with the liquid-phase rinsing and drying process into a single process vessel, to reduce the floor space and equipment required to process semiconductor wafers, or microelectronic workpieces in general.
SUMMARY OF THE INVENTION
[0009] In a first aspect of the invention, a processor for cleaning, rinsing, and drying a microelectronic workpiece includes a process vessel, an ozone or reactive gas or vapor supply system, a liquid injection system, and a drying system. The process vessel holds one or more workpieces. The ozone supply system introduces ozone gas into the process vessel. The liquid supply system introduces a processing liquid into the process vessel. The drying system provides a drying gas, vapor, or liquid.
[0010] In a second aspect of the invention, the processor according to the first aspect includes a gas bubbler for introducing ozone gas into the process vessel.
[0011] In a third aspect of the invention, a method for cleaning, rinsing, and drying a microelectronic workpiece inside a single process vessel includes the steps of first introducing a processing fluid into the process vessel with the processing fluid lying beneath the workpiece. Ozone gas is then preferably introduced into the process vessel. The workpiece is then immersed in the processing fluid. The processing fluid is removed from the process vessel and a drying fluid is then introduced into the process vessel. Use of a single vessel reduces floor space and handling requirements, and can expedite processing.
[0012] It is an object of the invention to provide an improved method and apparatus for cleaning, rinsing, and drying of a microelectronic workpiece. It is a further object of the invention to provide an improved method and apparatus that combines a vapor-phase cleaning process with a liquid-phase rinsing and drying process in a single processor or equipment.
[0013] The invention resides as well in subcombinations of the features and steps described. While use of ozone is preferred, it is not essential to the invention. Rather, the invention more broadly contemplates performing vapor phase process and then an immersion process and a drying process, in a single vessel regardless of the fluid chemicals used. A fluid here can be a liquid, a gas, or a vapor.
BRIEF DESCRIPTION OF THE DRAWING
[0014] [0014]FIG. 1 is a cut away perspective view of the cleaner/rinser/dryer system or processor.
DETAILED DESCRIPTION
[0015] Referring now to the FIG. 1, a processor 2 includes a process vessel or tank 4 . The processor 2 is used as a cleaner, rinser, and dryer for the processing of microelectronic workpieces 6 , including, for example, semiconductor substrates. The processor 2 is adapted to clean, rinse, and dry one or more workpieces 6 . Preferably, a batch of workpieces 6 are held within a cassette or holder 8 positioned within the process vessel 4 . The cassette 8 preferably contacts each workpiece 6 with a minimum number of contact locations.
[0016] In a preferred embodiment, the cassette 8 and the one or more workpieces 6 are held stationary within the process vessel 4 during the cleaning, rinsing, and drying process. The cassette 8 , however, may also be raised and lowered within the process vessel 4 during processing using known techniques. For stationary processing, the cassette or holder 8 may be held in place by a rack 10 located inside of the process vessel 4 . The processor 2 can also employ a motor 60 to spin the cassette or holder 8 , to provide more uniform processing. The spinning of the workpiece 6 is shown by the arrow 9 in FIG. 1. The workpieces are loaded and unloaded into the vessel 4 by opening or removing the vessel lid 5 . The lid 5 can, but need not, seal the vessel. Rather, the lid 5 helps to contain and control the vapor phase processing.
[0017] The process vessel 4 includes a liquid supply or injection system 11 that introduces, extracts, and replenishes processing fluid 16 within the process vessel 4 . The liquid injection system 11 includes one or more inlets 12 , and one or more outlets 14 , in the process vessel 4 for supplying and removing a processing fluid 16 . Preferably, the processing fluid is deionized (DI) water. The level of processing fluid 16 within the process vessel 4 may be controlled by varying the flow rates through the inlet 12 and outlet 14 . The flow rates are preferably controlled by a microprocessor-based controller.
[0018] The processor 2 also includes a drying system 17 connecting into the process vessel 4 . The drying system 17 operates by delivering a drying fluid such as a drying gas 24 into the process vessel. The drying system 17 may include a gas diffuser 18 located at the top of the process vessel 4 . The gas diffuser 18 advantageously includes a plurality of holes 20 to permit gas flow from above and into the vessel 4 . While rectangular-shaped orifices 20 are shown in FIG. 1, other shapes can also be used. One or more gas delivery pipes 22 are preferably connected to the gas diffuser 18 (if used) to supply a drying gas 24 to the process vessel 4 . The drying gas 24 may include any number of gases or gas mixtures. For example, the drying gas 24 might include N 2 , air, N 2 /air mixture, or an organic vapor 26 mixed with a carrier gas 28 .
[0019] [0019]FIG. 1 illustrates the gas delivery pipe 22 connected to separate sources for the organic vapor 26 and the carrier gas 28 , to provide surface tension effects for drying the workpieces 6 . The organic vapor 26 is preferably isopropyl alcohol (IPA). Of course, materials other than IPA may be used to promote drying. The carrier gas 28 is preferably N 2 , but other inert gases or even air can be used. The dilution of the combined organic vapor 26 and carrier gas 28 is preferably controlled by pressure regulators 30 . The combined gas stream is preferably pumped into the process vessel by pump 32 . A manifold 19 having spray nozzles may be used instead of the diffuser 18 .
[0020] If a single gas component is used for the drying gas 24 , the branch structure 33 shown in FIG. 1 is not necessary. The drying gas 24 is preferably directly pumped into the process vessel 4 . As an alternative to introducing the drying gas to the process vessel 4 via a gas diffuser 18 or the top manifold 19 , the drying fluid can be directly injected through one or more side nozzles 33 at the sides of the process vessel 4 . The drying fluid can be injected or sprayed as either a liquid or a gas depending on the drying fluid used. Various other drying systems, with or without IPA or other chemicals, may be used, including drying systems using heat, air or gas movement, mechanical liquid removal, or other techniques.
[0021] An overflow weir or wall 34 may be provided in the vessel, e.g., located on one side of the process vessel 4 . When the process fluid 16 rises to the level of the overflow weir 34 , the process fluid 16 passes over the overflow weir 34 and into a drain 36 . The overflow weir 34 ensures that the process vessel 4 does not overflow. In addition, the overflow weir 34 also serves as another outlet to remove processing fluid 16 that contains contaminants from the cleaning of the workpiece 6 . The overflow weir 34 , if used, can be located on any side of the process vessel 4 .
[0022] One or more heaters 38 are preferably, but not necessarily, provided and located on the side of the process vessel 4 . The heaters 38 are preferably located at a position that permits heat to be transferred from the heaters 38 to the processing fluid 16 . The heaters 38 , if used, may be positioned inside, within, or outside of the process vessel 4 . The heaters 38 are preferably controlled by a microprocessor-based controller to control the temperature of the processing fluid 16 within the process vessel 4 .
[0023] An ozone supply system 40 may be included for use in the vapor phase processing. If used, the ozone supply system 40 preferably includes a gas bubbler 46 connected via piping 47 to an ozone generator 42 . A pump 48 may be used to pump the ozone gas from the ozone generator 42 into the process vessel 4 . A flow control valve may also be used to control the flow of ozone gas into the process vessel 4 . A gas regulator 50 is preferably located upstream of the pump 48 . The ozone gas is preferably introduced into the process vessel 4 using the gas bubbler 46 . The gas bubbler 46 includes openings 52 that create bubbles 54 of ozone gas within the processing fluid 16 . As an alternative to the gas bubbler 46 , one or more ozone spray nozzles or even simple ports 56 can be positioned within the process vessel 4 to provide ozone gas directly into the process vessel 4 .
[0024] The process vessel 4 also preferably includes a gas vent 58 that permits the evacuation of gas from the process vessel 4 . The gas vent 58 is located on the top of the processor 2 or on the lid 5 .
[0025] In a preferred method, a cassette 8 containing a batch of workpieces is loaded into the processor 2 . Loading may be performed by opening or removing the lid 5 , and placing the cassette 8 onto a rack 10 within the process vessel 4 . The cassette 8 can also be loaded into the process vessel 4 via a robot. During the cleaning phase of the process, a processing fluid 16 such as DI water is introduced into the process vessel 4 via inlet 12 . The DI water level rises up from the bottom along the walls of the process vessel 4 . The level of the processing fluid 16 is raised to a first level shown by arrow A in FIG. 1. This first level is preferably below the bottom edge of the workpieces 6 held within the cassette 8 , so that the processing fluid 16 preferably does not contact the workpieces 6 .
[0026] Next, the heaters 38 are preferably used to heat the processing fluid 16 within the process vessel 4 . The processing fluid 16 is preferably heated to enhance the cleaning effect of the ozone gas on the workpiece 6 . Of course, the processing fluid 16 can also be heated before or while the processing fluid 16 is introduced into the process vessel 4 by the drying system. Once the appropriate temperature of the processing fluid 16 has been established, the ozone injection system 40 begins to inject ozone gas into the process vessel 4 . If used, the gas bubbler 46 bubbles ozone gas through the preferably heated processing fluid 16 . The ozone gas becomes heated and moist, thereby enhancing the cleaning effects of the ozone gas on the workpieces 6 . The ozone gas, if used, may alternatively be injected directly into the process vessel 4 via one or more nozzles 56 . The ozone gas is introduced into the process vessel 4 for a period of time sufficient to strip or remove any remaining photoresist or other contaminants from the workpieces 6 . Processing may also be performed at room temperature, without any heating, although heating is preferred.
[0027] After the vapor-phase cleaning step, the liquid-phase rinsing begins. Rinsing is important because the vapor phase cleaning step may not completely remove all contaminants. The level of the processing fluid 16 within the process vessel 4 is gradually increased to completely immerse the workpieces 6 . The processing fluid 16 stops rising when it reaches the top of the overflow weir 34 . This level is shown by arrow B in FIG. 1. At this point, the processing fluid 16 is preferably continuously refreshed to supply clean processing fluid 16 to the process vessel 4 . Processing fluid 16 containing contaminants passes out of the process vessel 4 via the overflow weir 34 and drain 36 , and optionally, the outlet 14 .
[0028] The processing fluid 16 used in this rinsing step is preferably, but not necessarily, the same fluid or the same type of fluid as used in the preceding cleaning step. This immersion step may also not necessarily be a rinsing step. Rather, if a process chemical liquid is provided into the vessel, this step may be a process step which chemically processes the workpieces. A rinsing step (using a rinsing liquid such as water) may then be subsequently performed, preferably in the vessel, but potentially also in another vessel.
[0029] After rinsing the workpiece, the drying step begins with the gradual reduction of the level of processing fluid 16 within the process vessel 4 via the outlet 14 . A drying gas 24 is preferably introduced into the process vessel 4 by the drying system 17 . The drying gas 24 may be introduced via the gas diffuser 18 located at the top of the process vessel 4 . If a liquid is used as the drying fluid, the liquid may be injected via injectors 33 . The drying gas 24 may alternatively be introduced via injectors 33 in the process vessel 4 . If surface tension effects are used, the drying gas 24 preferably includes an organic vapor component such as IPA to increase surface tension effect drying of the workpiece 6 .
[0030] At the end of the cleaning/rinsing/drying process, when the processing fluid 16 has been removed from the process vessel 4 , the workpieces 6 are removed from the processor 2 . While DI water has been described as the preferred processing fluid, other processing fluids 16 can also be used. In addition, multiple processing fluids 16 can be introduced into the process vessel 4 in a continuous or near-continuous manner. This allows different processing fluids 16 to replace each other. The processing fluid 16 inside the process vessel 4 is removed from the process vessel 4 either by the overflow weir 34 or the outlet 14 . The removed processing fluid 16 can then be returned to a process tank for recovery and reuse. Alternatively, the processing fluid 16 can be directed to a waste drain.
[0031] In another aspect of the invention a processor 2 of the type disclosed in pending U.S. patent application Ser. No. 09/590,724, filed Jun. 8, 2000, is used. This Application is incorporated by reference as if set forth fully herein. U.S. patent application Ser. No. 09/950,724 discloses a processor 2 that uses an outer containment vessel and a porous process vessel 4 to enhance drying.
[0032] While embodiments of the present invention have been shown and described, various modifications may be made without departing from the scope of the invention. The invention, therefore, should not be limited, except to the following claims, and their equivalents. | A processor for cleaning, rinsing, and drying workpieces includes a process vessel, an ozone injection system for introducing ozone gas into the process vessel, a liquid injection system for introducing a processing fluid into the process vessel, and a drying system for delivering a drying fluid to the process vessel. The processing fluid is introduced into the process vessel such that the processing fluid lies beneath a workpiece. Ozone gas is introduced into the process vessel. The workpiece is then bathed in the processing fluid. A drying fluid is introduced into the process vessel while the processing fluid is evacuated from the process vessel. Microelectronic workpieces can be cleaned and dried in a single vessel, reducing the equipment and space used in manufacturing. | 1 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention generally relates to a bicycle shift control device. More specifically, the present invention relates a cable operated bicycle shift control device that has an access opening for accessing the interior of the bicycle shift control device to perform maintenance.
2. Background Information
Bicycling is becoming an increasingly more popular form of recreation as well as a means of transportation. Moreover, bicycling has become a very popular competitive sport for both amateurs and professionals. Whether the bicycle is used for recreation, transportation or competition, the bicycle industry is constantly improving the various components of the bicycle.
For example, the front and rear shift control devices are often redesigned to make them easier to operate and easier to maintain. The shift control devices are coupled to a drive train having several gears, which are used on a bicycle in order to climb hills more easily, or to ride faster on flat ground. The shift control devices are each generally coupled to a shift mechanism such as a derailleur or an internally geared hub that is operated by a control cable.
There are many types of cable operated shift control devices currently being installed on bicycles. For example, some cable operated shift control devices have a pair of shift levers and a cable winding mechanism that rotates via a ratchet mechanism. With conventional cable operated shift control devices of this type, operation of one of the shift lever causes the cable winder to rotate via the ratchet mechanism in one direction by one gear. As a result, the cable is wound around the cable winder, and a shift is made by the shift mechanism from one gear to the next gear. Operation of the other shift lever causes the ratchet mechanism to be released and the cable winder to rotate in the other direction by one gear. As a result, the cable that was wound on the cable winder is played out, and a shift is made in the opposite direction by the shift mechanism.
Another example of a cable operated shift control device is a hand grip actuated shifter in which the hand grip rotates around the axis of the handlebar to rotate a cable take-up element. Thus, when the hand grip is rotated in one direction, the cable is wound around the take-up element to cause the derailleur or internal geared hub to shift from one gear to the next gear. Rotation of the hand grip in the other direction causes the cable to be unwound or played out so that the derailleur or internal geared hub shifts from one gear to the next gear.
One problem with these types of cable operated shift control devices is that the control cable sometimes breaks. Many of these shift control device have to be completely disassembled in order to replace the control cable. More recently, a maintenance hole has been provided for changing these control cables. These maintenance holes can allow dirt or other contaminants to enter the unit. Therefore, many control devices with maintenance holes have a plug for covering the hole. These plugs are typically separate parts that are prone to being lost. Moreover, often these plugs are difficult to remove without a tool.
In view of the above, there exists a need for an improved bicycle shift control device which overcomes the above mentioned problems in the prior art. This invention addresses this need in the prior art as well as other needs, which will become apparent to those skilled in the art from this disclosure.
SUMMARY OF THE INVENTION
One object of the present invention is to provide a bicycle shift control device with an access opening having a slideably maintenance cover for easy access to change the control cable.
The foregoing object can basically be attained by providing a cable operated bicycle shift control device that has an outer casing with a cable receiving bore and an access opening for accessing a cable operated winding mechanism to perform maintenance such as replacement of the cable. The cable operated winding mechanism is disposed in the outer casing such that its cable attachment point is disposed relative to the access opening to be accessible from the access opening. A maintenance cover slideably is coupled to the outer casing between a closed position overlying the access opening and an open position exposing the access opening.
These and other objects, features, aspects and advantages of the present invention will become apparent to those skilled in the art from the following detailed description, which, taken in conjunction with the annexed drawings, discloses a preferred embodiment of the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
Referring now to the attached drawings which form a part of this original disclosure:
FIG. 1 is a side elevational view of a conventional bicycle with a bicycle shift control device coupled thereto in accordance with one embodiment of the present invention;
FIG. 2 is a perspective view of the shift control device in accordance with the present invention;
FIG. 3 is a top plan view of the shift control device in accordance with the embodiment illustrated in FIG. 2;
FIG. 4 is a bottom plan view of the shift control device in accordance with the embodiment illustrated in FIGS. 2 and 3;
FIG. 5 is an exploded perspective view of the shift control device in accordance with the embodiment illustrated in FIGS. 2-4;
FIG. 6 is a partial side elevational view of the shift control device illustrated in FIGS. 2-5 with the maintenance cover in the closed position covering the access opening;
FIG. 7 is a partial side elevational view of the shift control device illustrated in FIGS. 2-5 with the maintenance cover in the open position exposing the access opening;
FIG. 8 is a partial top plan view of the shift control device illustrated in FIGS. 2-5 with the maintenance cover in the closed position covering the access opening;
FIG. 9 is a partial top plan view of the shift control device illustrated in FIGS. 2-5 with the maintenance cover in the open position exposing the access opening; and
FIG. 10 is a cross sectional view of the shift control device illustrated in FIGS. 2-9 as seen along section line 10 — 10 of FIG. 7 .
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring initially to FIGS. 1 and 2, a conventional bicycle 10 is illustrated having a shift control device 12 coupled to the handlebar 13 of the bicycle 10 in accordance with one embodiment of the present invention. Bicycles and their various components are well known in the prior art, and thus, the bicycle 10 and its various components will not be discussed or illustrated in detail herein, except for the components that relate to the present invention. In other words, only the shift control device 12 and the components that relate thereto will be discussed and/or illustrated herein.
In the illustrated embodiment, as best seen in FIGS. 2-5, the shift control device 12 is part of an integrated shifting and braking unit. In other words, the shift control device 12 is fixedly coupled to a lever bracket 14 that pivotally supports a brake lever 16 . Of course, it will be apparent to those skilled in the art from this disclosure that the shift control device 12 could be a separate unit from the brake lever 16 . Moreover, it will be apparent to those skilled in the art from this disclosure that this invention could be utilized with other types of shift control devices such as a hand grip actuated shift control device.
The shift control device 12 basically includes an outer casing 18 having a cable operated winding mechanism 20 disposed in the outer casing 18 , a pair of shift levers 22 and 24 , and a gear indicator 26 operatively coupled to the cable operated winding mechanism 20 .
The cable operated winding mechanism 20 and the gear indicator 26 are well known in the art. Thus, these parts will not be discussed or illustrated in detail herein. Moreover, it will be apparent to those skilled in the art from this disclosure that the precise structure of these parts is not crucial to the present invention. The illustrated embodiments of the cable operated winding mechanism 20 and the gear indicator 26 are disclosed in U.S. Pat. No. 5,701,786, assigned to Shimano Inc.
In the illustrated embodiment, the outer casing 18 is formed of four portions, i.e., a first or upper casing half 30 and a second or lower casing half 32 having a first lower casing portion 32 a , a second lower casing portion 32 b and a third lower casing portion 32 c . The lower casing portions 32 a - 32 c are fastened to the upper casing half 30 by a bolt 34 extending through the outer casing 18 and a nut 36 attached to an upper portion of the upper casing half 30 . The upper casing half 30 is integrally formed with the lever bracket 14 . Thus, when the upper and lower casing halves 30 and 32 are coupled together, the entire outer casing 18 is connected to the handlebar 13 through the mounting portion 14 a of the lever bracket 14 .
The shifting levers 22 and 24 and the cable operated winding mechanism 20 are attached to a support member 15 that is mounted within the outer casing 18 via the bolt 34 and the nut 36 . The shifting levers 22 and 24 are interlocked to the cable operated winding mechanism 20 through a take-up element 38 and a known ratchet-type interlock mechanism. This interlock mechanism includes a ratchet type feed pawl (not shown) for transmitting a pivotal movement of a shift lever 22 to the take-up element 38 , a positioning pawl (not shown) for returning the take-up element 38 in a predetermined rotational position, a limiter pawl (not shown) for limiting an unwinding rotation of the take-up element 38 , and a release cam (not shown) for disengaging the positioning pawl from the take-up element 38 .
By operating the shift levers 22 and 24 , the take-up element 38 is rotated to pull or release an inner wire 40 of the control cable 41 . For example, when the shift lever 22 is shifted in an upshift direction U from an original position N 1 , the take-up element 38 rotates in a winding direction to take up the inner wire 40 of the control cable 41 as seen in FIG. 4 . The shift lever 22 can be released after being operated a predetermined amount necessary for effecting a gear change. Then, the shift lever 22 automatically returns to the original position under the biasing force of a return spring (not shown). At this time, despite the return to the original position of the shift lever 22 , the take-up element 38 is retained in a position to which the take-up element 38 has been rotated by the shift lever 22 to complete the gear change. The shift lever 22 is shiftable in a downshift direction D from an original position N 2 as seen in FIG. 4 .
Thereafter, the shift lever 24 can be released to be returned to its original position by the biasing force of a return spring (not shown). Then, the take-up element 38 rotates by an angle of one pitch in the unwinding direction under the force of an unwind spring (not shown) and a restoring force of the shifting device (derailleur) provided by the inner wire 40 . Consequently, the shift control device 12 unwinds the inner wire 40 of the control cable 41 to effect a one-stage gear shift.
As best seen in FIG. 5, the outer casing 18 has a cable receiving bore 42 and an access opening 44 formed between the upper casing half 30 and the lower casing half 32 as well as a pair of shift lever openings 46 and 48 formed therebetween. As best seen in FIG. 10, the upper casing half 30 and the lower casing half 32 each includes curved L-shaped rails 50 and 52 that are vertically spaced apart to form a curved channel for slideably receiving a maintenance cover 54 . The rails are located so that the maintenance cover 54 can slide between closed position overlying the access opening 44 and an open position exposing the access opening 44 . The rails 50 and 52 are also provided with a stop 58 at one end to limit the movement of the maintenance cover 54 .
As best seen in FIGS. 8 an 9 , the maintenance cover 54 is a generally curved member having a curvature that conforms to the curvature of the outer surface of the outer casing 18 . Preferably, as seen in FIG. 10, the maintenance cover 54 has a pair of guide edges 54 a that are received between the rails 50 and 52 and the upper and lower casing halves 30 and 32 for slideably being received within the channel formed therebetween. As best seen in FIGS. 8 an 9 , the maintenance cover 54 is provided with a plurality of ribs 54 b that form a handle element, which is arranged to aid in moving the maintenance cover 54 between the closed and open positions. The ribs 54 b that form the handle element are located at one end of the maintenance cover 54 . The other or opposite end of the maintenance cover 54 is provided with a latching or locking arrangement that releasably locks the maintenance cover 54 in the closed position as seen in FIGS. 7 and 9.
In particular, the outer casing 18 and maintenance cover 54 include complementary retaining elements. Preferably, the maintenance cover 54 has a recess or notch 54 c that forms a first complementary retaining element while the outer casing 18 includes a second complementary retaining element in the form of a latching element or portion 56 . This latching element 56 can be a protrusion or merely edge portion of a part of the outer casing 18 . Thus, the notch 54 c engages the latching portion 56 of the upper and lower casings 30 and 32 to lock the maintenance cover 54 in the closed position. In particular, when the maintenance cover 54 is moved from the open position to the closed position, the end of the maintenance cover 54 with the notch 54 c will slide underneath the latching portion 56 of the upper and lower casing halves 30 and 32 to releasably lock the maintenance cover 54 in the closed position. Preferably, this locking arrangement is accomplished by having the maintenance cover 54 being flexed slightly inwardly towards the access opening 44 such that the maintenance cover 54 is elastically deformed. This results in the maintenance cover 54 applying an outwardly directing force on the latches to hold the maintenance cover 54 in the closed position.
It will be apparent to those skilled in the art from this disclosure that the upper and lower casings 30 and 32 and the maintenance cover 54 can be constructed of a variety of materials. These materials include various plastics and metals.
The terms of degree such as “substantially”, “about” and “approximately” as used herein mean a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms should be construed as including a deviation of at least ±5% of the modified term if this deviation would not negate the meaning of the word it modifies.
While only selected embodiments have been chosen to illustrate the present invention, it will be apparent to those skilled in the art from this disclosure that various changes and modifications can be made herein without departing from the scope of the invention as defined in the appended claims. Furthermore, the foregoing description of the embodiments according to the present invention are provided for illustration only, and not for the purpose of limiting the invention as defined by the appended claims and their equivalents. | A cable operated bicycle shift control device has an outer casing with a cable receiving bore and an access opening for accessing a cable operated winding mechanism to perform maintenance such as replacement of the cable. The cable operated winding mechanism is disposed in the outer casing such that its cable attachment point is disposed relative to the access opening to be accessible from the access opening. A maintenance cover movably is coupled to the outer casing between a closed position overlying the access opening and an open position exposing the access opening. | 1 |
INCORPORATION BY REFERENCE TO RELATED APPLICATIONS
Any and all priority claims identified in the Application Data Sheet, or any correction thereto, are hereby incorporated by reference under 37 CFR 1.57. This application is a continuation of U.S. application Ser. No. 13/710,842, filed on Dec. 11, 2012, which is a continuation of U.S. application Ser. No. 10/585,796, filed on Jul. 23, 2008, now U.S. Pat. No. 8,335,566, which is the national stage in the U.S. of PCT Application No. PCT/IB2005/050048, filed on Jan. 5, 2005, which claims the benefit of Swiss Patent Application No. 0040/04 filed Jan. 12, 2004. Each of the aforementioned applications is incorporated by reference herein in its entirety, and each is hereby expressly made a part of this specification.
BACKGROUND OF THE INVENTION
The present invention relates to the field of electrostimulation devices, in particular muscular electrostimulation devices.
More specifically, it relates to those electrostimulation devices that comprise a housing provided with at least one charger plug and one stimulation plug.
DESCRIPTION OF THE PRIOR ART
A number of styles of housings for electrostimulation devices are presented on the web site of the applicant (www.compex.info).
Normally, a housing for an electrostimulation device comprises a charger plug and a number of stimulation plugs designed to respectively receive a connector linked to an external charger and a number of connectors linked to stimulation electrodes.
The housing comprises an accumulator battery that is chargeable by direct current via the charger plug.
The electrostimulation is produced by means of electrodes applied to the skin of the user.
The stimulation current is limited to a few tens of milliamps (normally 120 mA maximum for a pulsed current).
A major risk is run by the user when the housing is linked both to the mains through the charger and to the user through the electrodes. In this configuration, if a fault were to occur in the external charger (insulation fault, component fault, etc.), the user could be directly linked to the mains voltage, which represents a mortal hazard. In practice, a link with the mains can provoke a cardiac fibrillation, a fainting fit, burns, pains, etc.
The housing disclosed in U.S. Pat. No. 4,421,001 offers a solution to this problem. It comprises a single plug that can operate alternately as a charger plug or a stimulation plug.
This solution does, however, present a number of drawbacks: it is not suited to housings that include a number of stimulation plugs and, furthermore, producing the dual-function plug is relatively complicated.
SUMMARY OF THE INVENTION
One objective of the invention is to increase the safety of the electrostimulation devices.
Another objective is to also offer a high level of safety for housings that include a number of stimulation plugs.
These objectives are achieved with a housing for an electrostimulation device that comprises a charger plug and a stimulation plug, designed to receive respectively a connector linked to a charger and a connector linked to stimulation electrodes. The housing according to the invention is characterized in that it also comprises a mobile locking element designed to alternately lock the charger plug or the stimulation plug.
The presence of the mobile locking element makes either the charger plug or the stimulation plug(s) available. The simultaneous availability of both types of plug is then impossible.
Particularly advantageous embodiments include a housing for an electrostimulation device that has a charger plug and a stimulation plug. The housing includes a mobile locking element that is designed to alternately lock the charger plug or stimulation plug. In another implementation, the mobile locking element presents an inclined surface inside the charger plug. Insertion of a connector into the charger plug exerts a force to displace the mobile locking element to lock the stimulation plug. In another implementation, the mobile locking element presents an inclined surface inside the stimulation plug. Insertion of a connector into the charger plug exerts a force to displace the mobile locking element to lock the charger plug. In another implementation, the charger plug and the stimulation plug are located on two opposite sides of the housing. The mobile locking element follows a curvilinear path. In another implementation the mobile locking element may include a thrust element which be activated by a user to release a plug.
Moving the mobile element from one position to the other can be done either manually, for example using a thrust element that the user moves, or as a consequence of inserting a connector into the plug that is blocked. In the latter case, the locking element comprises an inclined surface that is made apparent in the plug. When the connector is inserted into the plug, a force is exerted on the inclined surface, which causes the locking element to be displaced.
The invention will be better understood from reading the detailed description that follows and examining the appended drawings which represent, by way of nonlimiting example, an embodiment of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 presents a first embodiment of the invention with stimulation plugs available.
FIG. 2 presents the housing of FIG. 1 with a charger plug available.
FIG. 3 diagrammatically presents a locking principle according to the invention with stimulation plugs available.
FIG. 4 presents the object of FIG. 3 with a charger plug available.
FIG. 5 presents a second embodiment of the invention.
FIG. 6 presents a third embodiment of the invention with a stimulation plug available.
FIG. 7 presents the object of FIG. 6 with a charger plug available.
FIG. 8 presents a third embodiment of the invention with stimulation plugs available.
FIG. 9 presents the object of FIG. 8 with a charger plug available.
FIG. 10 presents a fourth embodiment of the invention with stimulation plugs available.
FIG. 11 presents the object of FIG. 10 with a charger plug available.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
In the various FIGS. 1-11 , illustrated are a housing 1 , a charger plug 2 , a stimulation plug 3 , a mobile locking element 4 , a locking element of the charger plug 5 , a locking element of the stimulation plug 6 , a thrust element 7 , and an inclined surface 8 .
The housing 1 represented in FIGS. 1 and 2 comprises a charger plug 2 and four stimulation plugs (each indicated by reference numeral 3 ).
FIGS. 3 and 4 diagrammatically represent in particular the design illustrated in FIGS. 1 and 2 . The housing 1 comprises two mobile locking elements 4 a and 4 b in strip form, which can be displaced in a direction parallel to the line passing through the plugs 2 , 3 . Each of strips 4 a and 4 b comprises a series of teeth 6 designed to lock the stimulation plugs 3 . The end of each strip 4 a and 4 b which culminates in the charger plug 2 comprises an inclined surface 8 . When the charger connector is inserted into the corresponding plug 2 , a force is exerted on the inclined surface 8 , which drives the strips towards the stimulation plugs 3 , simultaneously locking their access.
Preferably, springs (not shown) are associated with the locking strips 4 a and 4 b . They are located so as to return the locking strips 4 a and 4 b when all the connectors are removed from the housing 1 .
The locking elements 6 can take the form of teeth, as indicated previously. Alternatively, the locking strip 4 can include orifices (not shown) through which the plugs can pass. In this case, the locking elements are formed by the strip elements that are located between the orifices.
The embodiment diagrammatically illustrated in FIG. 5 comprises a locking rod 4 which pivots about its main axis. The locking elements 6 are angularly separated by 90° so that the charger 2 and stimulation plugs 3 are alternately locked.
The embodiment of FIG. 6 also presents a locking rod 4 that pivots, but in a direction perpendicular to the main axis of the rod. In the embodiment of FIGS. 8 and 9 , the charger plug 2 is located on a side of the housing 1 opposite to that where the stimulation plugs 3 are located. The mobile locking element 4 is formed by a semi-rigid tab, which is moved in response to the force exerted on the inclined surface 8 by the charger connector.
The embodiment of FIGS. 10 and 11 presents a mobile locking element 4 that is mobile in a vertical direction. In the configuration illustrated in FIG. 2 , a spring (not shown) holds the mobile element 4 in a bottom position (rest position). The upward movement of the mobile element 4 is obtained manually through the intermediary of a thrust element 7 that the user must push upward.
The locking element 5 of the charger plug 2 is in the form of an inverted L. Four locking elements 6 for stimulation plugs 3 are located along the mobile locking element 4 , perpendicular to the latter.
In the rest position ( FIG. 10 ), the locking element of the charger plug 5 blocks the charger plug 2 . The stimulation plugs 3 are available and can accommodate stimulation connectors.
If the user wants to insert the charger plug, he must first remove the stimulation connectors, push the thrust element 7 upward and insert the power supply connector.
Once this operation is completed ( FIG. 11 ), the stimulation plugs are blocked by the corresponding locking elements 6 .
According to the variant of the invention that is not shown, the thrust element 7 is eliminated. In this case, the locking element 5 of the charger plug 2 comprises an inclined surface of a form and function identical to that described previously.
Obviously, the invention is not limited to the above-mentioned examples. | A housing for an electrostimulation device comprising a charger plug and a stimulation plug, designed to receive respectively a connector linked to a charger and a connector linked to a stimulation electrode, characterized in that it comprises a mobile locking element designed to alternately lock the charger plug or the stimulation plug. | 0 |
TECHNICAL FIELD
[0001] The present invention relates to a mechano-responsive composition capable of changing colour when subjected to mechanical stimuli.
BACKGROUND
[0002] Polymer materials are ubiquitous in everyday life and are used in various applications (such as, medicals, automobiles, electronics, structures, etc.). These materials experience stress during the normal use, which can lead to damage and failure of the product. Having the ability of detecting damage and locating areas under high stress in situ is essential to eliminating failure of the polymer materials.
[0003] Mechano-responsive luminescent materials change the colour of their luminescence isothermally, and because these changes can be easily detected, they have potential use for practical applications such as mechano-sensors, indicators of mechano-history, security papers, opto-electronic devices and data storage. For example, deformation, distortion and destruction of various materials can be detected more easily through mechanochromic luminescent materials than using traditional methods. These sensing properties can also be useful for the maintenance of materials because they can easily show where the damage has occurred.
[0004] The simplest manner to provide a mechanochromic material is to incorporate a coloured substance into the matrix in the form of capsules or hollow fibers, as described in WO2007/003883A1. Initially, the colour is not visible. Upon damage to the matrix, the capsules or fibers rupture and expose the coloured substance, such as a fluid or solid. WO2006/105290A2 discloses a two-part system, wherein a colourless compound is mixed with an activator. Upon the rupture of their respective containers, a colour change is trigged. A disadvantage of these systems is that the fibers and capsules need to be evenly dispersed throughout the matrix, so that the damage inducing force has a large chance to intersect the capsules or fibers.
[0005] U.S. Pat. No. 7,242,443B2 discloses another approach, wherein triboluminescent materials are used to give off flashes of light in response to stress or damage. When damage occurs, these materials require continuous monitoring to detect due to the transient nature of the light flash.
[0006] U.S. Pat. No. 7,244,500B2 discloses smart coatings consisting of several layers of sensing materials. These coatings are complex and require external power to accomplish many of their tasks.
[0007] U.S. Pat. No. 8,236,914B2 discloses a self-assessing mechanochromic material, which is a mechanochromic material including a polymer having a backbone containing a mechanophore.
[0008] Nallicheri, et al. (“ Investigations of the Mechanochromic Behavior of Poly ( urethane - diacetylene ) Segmented Copolymers”, Macromolecules, 1991, pp. 517-525, Vol. 24, No. 2) discloses a diacetylene segmented copolymer, which exhibits a shift of colour when subjected to a strain.
[0009] Todres (“ Recent advances in the study of mechanochromic transitions of organic compounds”, J. of Chemical Research, 2004, 89-93) outlines several organic compounds possessing mechanochromic properties. Specifically, spiropyran has been noted to undergo a colour change upon grinding. However, few applications exist for the small molecule alone. Weder and coworkers (Weder, C. Mechanochemistry: Polymers react to stress. Nature 459, 45-46 (2009)) have incorporated cyano-substituted oligo(p-phenylene vinylene) derivatives into different polymer matrixes and have synthesized “self-assessing” polyurethanes, polyethylene blends, poly(ethylene terephthalate)s, and poly(ethylene terephthalate glycol)s. Their approach relies on the initial formation of nanoscale aggregates of the sensor molecules in the polymer matrix. Upon deformation, the cyano-substituted oligo(p-phenylene vinylene) sensors are transformed from excimer to monomer and a shift in the emission spectrum is observed. Most of these sensing units are not chemically incorporated into the backbone, and exhibit only a fluorescent colour change that is not visible to the naked eye. Additionally, these materials are not reversible in colour change and can only exhibit a colour change once.
[0010] Kim and Reneker (“ A mechanochromic smart material”, Polymer Bulletin, 31, 1993, 367-374) introduced azobenzene into a copolyamide oligomer, which was chemically incorporated into a polyurethane. Upon exposing the material to tensile stress, a change in the UV spectrum at 375 nm was observed. However, no visible change was noted and the polymer had to be irradiated with UV light prior to stressing the materials.
[0011] In the recent patent document WO 2009018111 A1, David and his coworkers presented a mechanochromic material comprising a polymer having a backbone containing a mechanophore, which is used as an additive to get colour change under mechano-force.
[0012] The number of mechano-responsive luminescent materials based on molecular assemblies is still limited, compared with that of dynamic luminescent materials responding to heat or light.
[0013] In most of the reported mechanochromic materials, an additive having a mechanochromic property, such as, a dye or a luminescence agent, was used as luminescence resource in the polymer matrix.
[0014] The problem to be solved by the present invention is to provide a mechanochromic material which has mechanochromic properties without the need of an additional mechanochromic component, such as a dye or a luminescence agent. It should be a simple system with only a few components so that the production and use are simplified. Additionally, it would be beneficial that the response to mechanical stimuli could be observed within the visible light spectrum. Preferably, the mechanochromic material should be able to recover so that its mechanochromic response is reversible and the material can be used longer and indicates several mechanical stimuli.
SUMMARY OF THE INVENTION
[0015] In the present invention, a two-part composition is provided having mechano-responsive property without adding any dyes or luminescence agents, and by subjected to mechanical stimuli, the cured composition changes its colour, and the colour is in the visible spectrum range, which can be easily checked with naked eyes; and the colour change is reversible.
[0016] In one aspect, the present invention provides a two-part mechano-responsive composition, comprising:
[0017] Part I: a tetra-glycidyl amine multifunctional epoxy resin represented by the general formula (I); and
[0018] Part II: a polythiol and as catalyst an amine;
[0000]
[0000] wherein,
[0019] R1 represents a linear or branched, unsubstituted or substituted alkylene group having 1 to 10 carbon atoms, an unsubstituted or substituted arylene group having 6 to 20 carbon atoms, or a combination of the alkylene and the arylene.
[0020] R2, R3, R4 and R5, independently each other, represent a direct bond, a linear or branched, unsubstituted or substituted alkylene group having 1 to 10 carbon atoms, an unsubstituted or substituted arylene group having 6 to 20 carbon atoms, or a combination of the alkylene and the arylene.
[0021] More than 50% of the polythiol carries at least three thiol groups (—SH) per molecule.
[0022] The amine is a catalyst for epoxy-thiol curing systems. Preferred is a tertiary amine.
[0023] Another aspect of the present invention is to provide a process for producing a mechano-responsive material using the composition of the present invention, comprising: blending the tetra-glycidyl amine multifunctional epoxy resin, the polythiol, the amine and optional additives together, and curing the mixture to obtain the mechano-responsive material.
[0024] Still another aspect of the present invention is to provide a mechano-responsive material produced by using the composition of the present invention.
[0025] Still another aspect of the present invention is the use of the two-part composition, comprising, as Part I, a tetra-glycidyl amine multifunctional epoxy resin represented by the general formula (I) and, as part II, a polythiol and as catalyst an amine, to produce a cured mechano-responsive material.
[0026] Advantages of the present invention are that no dyes or luminescence agents need to be added into the composition, and the colour change of the cured composition derives from the formed structure; meanwhile, the colour change is reversible and is in the visible spectrum range, which can be checked with naked eyes.
BRIEF INTRODUCTION OF THE DRAWINGS
[0027] FIG. 1 is a graph of the absorption spectrum of the cured composition of the present invention before and after applying an outside force, measured by a UV-Vis spectrophotometer.
DETAILED DESCRIPTION OF THE INVENTION
[0028] The present invention will be described in details as followings. The materials, methods, and examples herein are illustrative only and, except as specifically stated, are not intended to be limiting. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described herein.
[0029] All publications and other references mentioned herein are explicitly incorporated by reference in their entirety.
[0030] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as commonly understood by those skilled in the art. In case of conflict, the present specification, including definitions, will control.
[0031] Unless stated otherwise, all percentages, parts, ratios, etc., are by weight.
[0032] Where a range of numerical values are recited herein, unless otherwise stated, the range is intended to include the endpoints thereof, and all integers and fractions within the range.
[0033] Use of “a” or “an” is employed to describe elements and components of the present invention. This is done merely for convenience and to give a general sense of the invention. This description should be read to include one or at least one and the singular also includes the plural unless it is obvious that it is meant otherwise.
[0034] Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of ingredients, reaction conditions, or defining ingredient parameters used herein are to be understood as modified in all instances by the term “about”.
[0035] The terms “mechano-responsive (luminescent) material”, “mechanochromic (luminescent) material” used in the context all refer to those materials capable of changing colour when subjected to mechanical stimuli, and can be used interchangeably.
[0036] As mentioned above, one aspect of the present invention is to provide a two-part mechano-responsive composition, comprising: Part I: a tetra-glycidyl amine multifunctional epoxy resin represented by the general formula (I); and Part II: a polythiol and as catalyst an amine.
[0037] Each component in the composition of the present invention will be described in detail as below.
Part I: Tetra-Glycidyl Amine Multifunctional Epoxy Resin
[0038] The tetra-glycidyl amine multifunctional epoxy resin used in the present invention has a structure of the general formula (I):
[0000]
[0000] wherein,
[0039] R1 represents a linear or branched, unsubstituted or substituted alkylene group having 1 to 10 carbon atoms, an unsubstituted or substituted arylene group having 6 to 20 carbon atoms, or a combination of the alkylene and the arylene.
[0040] Examples of the substitutent on the alkylene include an aryl group having 6 to 20 carbon atoms, for example, phenyl and biphenyl.
[0041] When R1 represents an alkylene, preference is given to a linear or branched, unsubstituted alkylene group having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, such as, methylene, ethylene, propylene, butylene, amylene, hexylene, heptylene, octylene, nonylene, decylene, and all isomers of them.
[0042] Examples of the substitutent on the arylene include an alkyl group having 1 to 10 carbon atoms, i.e., having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, such as, methyl, ethyl, propyl, butyl, amyl, hexyl, heptyl, octyl, nonyl, decyl, and all isomers of them.
[0043] When R1 represents an arylene group, preference is given to an unsubstituted arylene having 6 to 20 carbon atoms, such as, phenylene, biphenylene or phenylene-biphenylene.
[0044] When defining the carbon atom number of a group in the context, the defined number does not include the carbon atoms of the substituent(s). For example, the expression “alkylene having 1 to 10 carbon atoms” only define the carbon atom number of the alkylene. However, as for the branched alkylene or alkyl, the carbon atoms in the branches are included in the defined carbon atom number. For example, the groups —CH 2 CH 2 CH 2 CH 2 —, —CH(CH 3 )CH 2 CH 2 —, —CH(CH 2 CH 3 )CH 2 — and —CH(CH 2 (CH 3 ) 2 )— all belong to “an alkylene having 4 carbon atoms”, and the group —CH(phenyl)CH 2 — belongs to “an alkylene having 2 carbon atoms substituted with a phenyl”.
[0045] From the point view of practical use, in order to ensure heat resistance of the cured composition, it is preferred that R1 contains at least one arylene group in the backbone. For example, the alkylene and the arylene may present alternately in the backbone of group R1, in such a manner, one or more, for example, two or three or four, alkylene groups and one or more, for example, two or three or four, arylene groups may be included.
[0046] When R1 represents a combination of the alkylene and the arylene, especially, the alkylene and the arylene present alternately in the backbone of group R1, R1 may have a structure selected from the following formulae, for example:
[0000]
[0000] wherein,
[0047] L in each occurrence independently represents a linear or branched alkylene group having 1 to 10 carbon atoms, i.e., having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, such as, methylene, ethylene, propylene, butylene, amylene, hexylene, heptylene, octylene, nonylene, decylene, and all isomers of them; preferably, a linear or branched alkylene group having 1, 2, 3, 4 or 5 carbon atoms, such as, methylene, ethylene, propylene, butylene or amylene;
[0048] R in each occurrence independently represents an alkyl group having 1 to 10 carbon atoms, i.e., having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, such as, methyl, ethyl, propyl, butyl, amyl, hexyl, heptyl, octyl, nonyl, decyl, and all isomers of them, or an aryl group having 6 to 20 carbon atoms, for example, phenyl and biphenyl; preferably, an alkyl group having 1, 2 or 3 carbon atoms, such as, methyl, ethyl or propyl; and
[0049] n in each occurrence independently is an integer of 0 to 4, such as, 0, 1, 2, 3 or 4, preferably, 0 or 1, more preferably, 0.
[0050] From the view point of practical use, most preferred structure for R1 in the present invention is:
[0000]
[0000] wherein L, R and n have the same meanings as defined above.
[0051] R2, R3, R4 and R5, independently each other, represent a direct bond, a linear or branched, unsubstituted or substituted alkylene group having 1 to 10 carbon atoms, an unsubstituted or substituted arylene group having 6 to 20 carbon atoms, or a combination of the alkylene and the arylene.
[0052] Preferably, R2, R3, R4 and R5, independently each other, represent a direct bond, or a linear or branched alkylene group having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms; such as, methylene, ethylene, propylene, butylene, amylene, hexylene, heptylene, octylene, nonylene, decylene, and all isomers of them. More preferably, R2, R3, R4 and R5, independently each other, represent a direct bond, a methylene or an ethylene; most preferably, a direct bond.
[0053] The tetra-glycidyl amine multifunctional epoxy resin may be used in the composition of the present invention alone or in a mixture.
[0054] The commercially available examples of the tetra-glycidyl amine multifunctional epoxy resin include, but not limited to, LY5056, MY720, MY721, XB9721, MY9512, MY9612, MY9634, MY9655 and MY9663 from Huntsman under the trademark of Araldite®; AG 80 from Shanghai Institute of Organic Synthesis; Jeh 011 from Changshu Jiafa Chemical Company. These resins can be used alone or in combination of any ratio.
Part II: Polythiol
[0055] More than 50% of the polythiol carries at least three thiol groups per molecule. The thiol groups may be primary thiol groups or secondary thiol groups or combinations thereof.
[0056] The definition “more than 50% of the polythiol carries at least three thiol groups per molecule” in this context may be understood as follows: one or more polythiols may be used in the composition of the present invention; when only one polythiol is used in the invention, the polythiol should comprise at least three thiol groups per molecule; while when more than one polythiol is used in the invention, more than 50% of the polythiol, for example, more than 70%, more than 80%, more than 90%, more than 98%, or 100% of the polythiol should carry at least three thiol groups per molecule, and other polythiol may comprise less than three thiol groups in one molecule. Preferably, 100% of the polythiol carries at least three thiol groups per molecule.
[0057] The definition “at least three” in this context may be understood as a number range including 3 and any integers bigger than 3, for example, 3.0 to 10, or 3.0 to 8.0, or 3.0 to 6.0, such as, 3.0, 4.0, 5.0, 6.0 and so on.
[0058] Preferred examples of the polythiols used in the present invention include, but not limited to,
[0000]
[0059] These thiols can be used alone or in combination of any ratio.
[0060] To obtain a sufficient curing of the composition and maintain the mechanochromic property, the molar ratio between the epoxy group and the thiol group (—SH) in the composition may be in the range of 1:0.8 to 1:1.4, preferably 1:1.
[0061] The amount of the polythiol used in the composition may be adjusted according to the polythiol used and the required properties of the cured material. For example, based on 100 parts by weight of the tetra-glycidyl amine multifunctional epoxy resin, the amount of the polythiol may be 80 to 150 parts by weight, preferably, 120 to 140 parts by weight.
Part II: Amine
[0062] The amine is a catalyst for epoxy-thiol curing systems. Preferred is a tertiary amine. The amine can be used alone or in combination of any ratio.
[0063] Examples of the amine include trimethylamine, triethylamine, tetraethylmethylenediamine, tetramethylpropane-1,3-diamine, tetramethylhexane-1,6-diamine, pentamethyldiethylenetriamine, pentamethyldipropylenetriamine, bis(2-dimethylaminoethyl)ether, ethylene glycol(3-dimethyl)aminopropyl ether, dimethylaminoethanol, dimethylaminoethoxyethanol, N,N,N′-trimethylaminoethylethanolamine, dimethylcyclohexylamine, N,N-dimethylaminomethylphenol, N,N-dimethylpropylamine, N,N,N′,N′-tetramethylhexamethylenediamine, N-methylpiperidine, N,N′-dimethylpiperazine, N,N-dimethylbenzylamine, dimethylaminomethylphenol, 2,4,6-tris(dimethylaminomethyl)phenol, 1,8-diazabicycloundecene-7, 1,5-diazabicyclononene-5, 6-dibutylamino-1,8-diazabicycloundecene-7, 1,2-dimethylimidazole, dimethylpiperazine, N-methyl-N′-(2-dimethylamino)ethylpiperazine, N-methylmorpholine, N-(N′,N′-(dimethylamino)ethyl)morpholine, N-methyl-N′-(2-hydroxyethyl)morpholine, triethylenediamine and hexamethylenetetramine. Of these, N,N-dimethylbenzylamine (DMBA), 2,4,6-tris(dimethylaminomethyl)phenol, bis[(dimethylamino)methyl]phenol and mixtures thereof are particularly preferable.
[0064] The amount of the amine used in the composition may be adjusted by those skilled in the art according to the practical use. For example, based on 100 parts by weight of the tetra-glycidyl amine multifunctional epoxy resin, the amount of the amine may be 1 to 4 parts by weight, preferably, 2 to 3 parts by weight.
Additives
[0065] Besides the components discussed above, the composition of the present invention may comprise any commonly used additives according to actual requirements, for example, diluents such as neopentyl glycol diglycidyl ether (for example, ED 523T from ADEKA), or trimethylolpropane triglycidyl ether (for example, DYT from Huntsman); fillers such as BaSO 4 , CaCO 3 and talc; tougheners such as MX153, MX154 (from KANEKA); pigments; rheological modifiers such as fumed silica (for example, TS 720 from Carbot) and the like.
[0066] Another aspect of the present invention is to provide a process for producing a mechano-responsive material using the composition of the present invention, comprising: blending the tetra-glycidyl amine multifunctional epoxy resin, the polythiol, the amine and optional additives together, and curing the mixture to obtain the mechano-responsive material.
[0067] The key point of the present invention is the incorporation of the tetra-glycidyl amine multifunctional epoxy resins and the polythiols discussed above into the composition. Other components or curing procedures may be the same as those common epoxy-thiol curing systems. And thus, the blending and the curing can be carried out by any technical means used in the art under suitable conditions that may be adjusted according to actual requirements.
[0068] Still another aspect of the present invention is to provide a mechano-responsive material produced by using the composition of the present invention.
[0069] Another aspect of the present invention is the use of a two-part composition, comprising, as Part I, a tetra-glycidyl amine multifunctional epoxy resin represented by the general formula (I) and, as part II, a polythiol and as catalyst an amine, to produce a cured mechano-responsive material.
Examples
[0070] The present invention will be further described and illustrated in details with reference to the following examples, which, however, are not intended to restrict the scope of the present invention.
Materials Used in the Examples
[0000]
DER 331, from Dow chemicals, is a liquid reaction product of epichlorohydrin and bisphenol A.
EPON Resin 828, from Hexion, is an undiluted clear difunctional bisphenol A/epichlorohydrin derived liquid epoxy resin.
MY 721, XB 9721, MY 9512, MY9634, and MY9655, from Huntsman, all of them are tetrafunctional amine epoxy resins.
AG 80, from Shanghai Institute of Organic Synthesis, is a tetrafunctional amine epoxy resin.
Jeh 011, from Changshu Jiafa Chemical Company, is a tetrafunctional amine epoxy resin.
Capcure 3-800, from BASF, is a mixture of mainly bifunctional and minor trifunctional polythiols.
TMTG, PETG, TMTP, PETP, all from KUDO Chemicals, are polythiols having at least three thiol groups.
PE 1, from Showdeno, is PETB, a polythiol having four thiol groups.
Ancamine 2636, from Air Products, is a modified aliphatic amine.
DMBA, from Aldrich, is N,N-dimethylbenzylamine.
DMP-302, from Aldrich, is 4,6-tris(dimethylaminomethyl)phenol.
EH 30, from BASF, is a mixture of 2,4,6-tris-(dimethylaminomethyl)-phenol and bis[(dimethylamino)methyl]phenol.
Examples 1-6 and Comparative Examples CE1-CE4
[0083] Examples 1-6 and comparative examples CE1-CE4 were carried out using the components and amounts thereof as listed in table 1. In each case, Components were mixed together by Speedmixer (from THINKY) with 2000 rpm and under 0.2 kPa vacuum. Then, the blended liquid mixture was poured into models with different shapes, such as, dog-borne, round or ball shapes. The curing condition was 3 hours at room temperature, or 5 minutes at 80° C. After curing, yellow-colour products were obtained in all cases.
Mechano-Responsive Property Test
[0084] To the obtained products, an outside force, such as scrapping, pressing, stretching or cutting, was applied. Visually check the colour change and the colour recovery. The results are shown in Table 1.
[0085] In addition, an absorption spectrum of the cured composition from Example 1 was tested before and after applying an outside force using a UV-Vis spectrophotometer. It can be seen that before applying the outside force, there is no absorption in the wavelength range of the red colour, which is the complementary colour of the green colour; and after applying the outside force, an absorption peak appears in red colour range, which indicates that the green colour appears.
[0000]
TABLE 1
Ex.
Ex.
Ex.
Ex.
Ex.
Ex.
CE.
CE.
CE.
CE.
Components
1
2
3
4
5
6
1
2
3
4
Epoxy
DER 331
50
100
resin
EPON
50
828
MY 721
100
50
60
100
100
XB 9721
100
40
MY 9512
10
MY9634
50
MY9655
50
AG 80
100
20
Jeh 011
20
polythiol
Capcure
130
3800
TMTG
30
PETG
20
TMTP
30
PETP
40
PE 1
120
100
100
110
80
130
130
120
amine
DMBA
2
2
4
3
DMP-30
2.5
1.5
3
3
EH 30
1.5
1
2.5
2.5
Ancamine
130
2636
Visible colour change
Yes
Yes
Yes
Yes
Yes
Yes
No
No
No
No
Visible colour recovery
Yes
Yes
Yes
Yes
Yes
Yes
—
—
—
—
Notes:
unit for each value is parts by weight.
[0086] In Examples 1-6, using components falling in the scope of the present invention, the obtained products changed their colour from yellow to green when subjected to the mechanical stimuli, and the green colour recovered to yellow again by keeping at room temperature for 12 h or heating at 80° C. for 1 h.
[0087] In Comparative Examples 1-4 (CE. 1-4), the obtained products do not exhibit colour change when subjected to the mechanical stimuli.
[0088] The present invention is illustrated in details in the embodiments; however, it is apparent for those skilled in the art to modify and change the embodiments without deviating from the spirit of the invention. All the modifications and changes should fall in the scope of the appended claims of the present application. | The present invention provides a two-part mechano-responsive composition, comprising: Part I: a tetra-glycidyl amine multifunctional epoxy resin represented by the general formula (I);
and Part II: a polythiol and an amine. The cured composition has a mechano-responsive property without adding any dyes or luminescence agents, and by subjected to mechanical stimuli, the cured composition changes its colour, and the colour is in the visible spectrum range, which can be easily checked with naked eyes; and the colour change is reversible. | 2 |
FIELD OF THE INVENTION
[0001] This invention relates to the safe and effective treatment of lice, nits (and other infestational insects) by using low surface tension lubricants.
BACKGROUND OF THE INVENTION
[0002] For centuries, people have been plagued by head lice, body lice, and pubic lice, which appear in numerous species all having similar physiological characteristics. Over the years, people have expended tremendous efforts and resources to develop a safe and effective method for eliminating the problem of lice and nits. To date, the only patented processes for killing lice and nits involve the use of poisons, pesticides or noxious soaps with numerous side effects and cautionary uses. These pediculicides, such as lindane, pyrethrun, or malathion, are not optimal for the treatment of lice or nits because they are not healthful, and because, over time, lice tend to develop a natural resistance to poison or pesticide formulation.
SUMMARY OF THE INVENTION
[0003] It is accordingly an object of the present invention to provide a method and chemical formulation for effective yet safe treatment for body insect infestation such as lice, fleas, and the like.
[0004] Generally present the invention compromises the direct treatment of body insect infestation with a synthetic lubricant, such as food grade silicon, to effectively kill infesting insects such as lice, and nits, as well as fleas, ticks and other insects. In Accordance with the present invention, the synthetic lubricant is applied directly to the insects, or is provided as a major (more than 50 volume percent) of a shampoo formulation. If added to a shampoo, the exact effective concentration level above 50% is determined based on both the nature of the synthetic lubricant, and the nature of the shampoo used.
DETAILED DESCRIPTION OF THE INVENTION
[0005] In order to illustrate the efficacy of the present invention the following test examples are presented.
EXAMPLE 1
[0006] Two tests were conducted using a compound containing 60% silicone-based oil. In the first test the compound was placed on a louse on a paper towel. After 5 minutes, the louse washed off with Prell® shampoo and water. The louse was observed one minute later and was dead. In the second test using the same compound, the compound was applied to the long, thick hair of a school girl, which had been infested with lice for several months. After five minutes, the compound was removed by several washes with Prell® shampoo, with the compound being otherwise difficult to extract from the hair. The infestation was successfully treated and no lice or nits returned.
EXAMPLE 2
[0007] Additional tests were conducted using a 100% concentration of Dow corning Fluid Food Grade silicone (350 CST) (the “silicone”). These tests also revealed that, in addition to killing lice, the silicone was effective at preventing nits from maturing. In these tests, silicone was applied directly to head lice, body lice, and to the hair of several children infested with head lice.
[0008] In the first Silicone experiment three head lice were collected from school children. The lice were placed on the hand of a subject and they attached themselves to the hair on the subject's hand. After five minutes, the lice were gently washed off with Prell® shampoo and then water.
[0009] Although there appeared to be mortality within minutes, the lice were left on the hand for further examination (they were covered with a loosely fitting bandage to make sure they did not fall off). During the following six hours, the lice were checked periodically and all were found to be dead.
EXAMPLE 3
[0010] In a further Silicone experiment, Silicone was directly applied to the hair of three school children, each of which had been infested with lice and nits. Each of the children applied the silicone directly to his or her hair and left it on for five minutes. After five minutes, the hair was washed first with Prell® shampoo and then with Johnson's Baby Shampoo®. In all three cases the infestation was successfully ended with one application.
[0011] In a continuing experiment, Silicone was directly applied to the hair of twenty school children, each of which had been infested with lice and nits. Each of the children applied the silicone directly to his or her hair and left it on for ten minutes minutes. After ten minutes, the hair was washed with a shampoo of the parent's choice. In all twenty cases the infestation was successfully ended with one application.
EXAMPLE 4
[0012] In another experiment ten adult lice were immersed in the Silicone for ten minutes, then washed and rinsed for one minute each in water. A set of ten control lice were immersed in water for ten minutes and then also washed and rinsed for one minute. The lice were then held in an incubator. A review of the lice after one hour, and again after twenty-four hours, revealed a 100% morality of those who had been immersed in Silicone. There was no morality among the controls.
EXAMPLE 5
[0013] In an additional experiment, ten adult lice were immersed in the Silicone for ten minutes, and subsequently washed in a dilution of 50:50 Johnson's Baby Shampoo® and tap water. To test the effectiveness at different concentrations of Silicone, four mixtures were made using the Silicone with Johnson's Baby Shampoo® with the following concentrations:
[0014] a. 100% Johnson's Baby Shampoo
[0015] b. 3% Silicone and 97% Johnson's Baby Shampoo
[0016] c. 15% Silicone and 85% Johnson's Baby Shampoo
[0017] d. 40% Silicone and 60% Johnson's Baby Shampoo
[0018] e. Control with water
[0019] The results of the test after 24 hours were that for samples a and c, one louse was dead; for samples b and e, no lice were dead. The one louse being dead was considered not statistically significant. In sample d, containing 40% Silicone, four lice were dead, indicating that at this concentration there is some effectiveness of the Silicone in killing lice but not a fully useful concentration. It is believed that other ingredients may interfere with the effectiveness of the Silicone, and accordingly it is preferred to use the Silicone in a high concentration or in a pure state.
EXAMPLE 6
[0020] In another experiment to determine the effect of lubricants of various surface tensions, a test was done using 10 adult lice immersing them into one of three solutions for ten minutes and then washing them of with a soapy water solution. The three lubricants used were Johnson's baby oil a mineral oil, Ultra pure lamp oil 99% pure liquid paraffin, and Krytox® 1514 Vacuum pump fluid, produced by Dupont®. The lice were then observed after one hour, and three hours and the amount dead were the same at both intervals in all tests. The mortality rate was highest for the Krytox® 1514 with nine of ten dead within one hour, lowest for the liquid paraffin with three of ten dead within one hour, and moderate for the mineral oil with four of ten dead within one hour. In a repeat of the experiment for the Krytox, seven out of ten where dead within one hour, for liquid paraffin two out of ten, and for mineral oil five out of ten.
[0021] The preferred embodiment for use as a head lice treatment is to use the Silicone in its pure state, that is Dow Coming 200 fluid, 350 CST. Which is a silicone fluid termed Dimethyl polysiloxane. The Silicone is water white and has a consistency of light syrup. This form is preferred as it clings easily to the hair. The Silicone is applied to the entire head, left on for at least ten minutes, and then washed off with any standard shampoo. Within a short time after application of the shampoo, the area is free of any live lice. Any nits do not mature.
[0022] Other embodiments include the processing of synthetic lubricants into a shampoo that effectively kills ticks, fleas, and other insects. The concentration of such lubricants, and the amount of time they must remain on the affected area, is above 50% by volume and is adjusted depending on the type of insect being treated. Thus, for example, in two experiments conducted on ticks, the ticks took longer to die than the lice did in the prior experiments using pure Silicone treatment. In the first tick experiment, ten Amblyomma Americanum ticks were coated with Silicone, and ten were coated with Prell® Shampoo. After ten minutes, both sets of ticks were washed with water and Prell® Shampoo for five minutes, until all of the Silicone and shampoo were removed. While all of the “Silicone” ticks were alive after one hour, after six hours three of the ticks were dead, five were morbid, and two were alive. After twenty-four hours, all of the “Silicone” ticks were dead, whereas only two of the “Prell®” ticks were dead.
[0023] In a second tick experiment, ten Dermacentor Varibilis ticks were coated with Silicone. After ten minutes all of the ticks were still alive. After ninety minutes, all of the ticks were dead.
[0024] While Silicone has been used for many years as a hair-bodying agent, and there are many patents (U.S. Pat. No. 3,964,500, U.S. Pat. No. 4,427,557, U.S. Pat. No. 4,465,619, U.S. Pat. No. 4,704,272, U.S. Pat. No. 5,728,457, U.S. Pat. No. 4,749,732, U.S. Pat. No. 4,842,850, U.S. Pat. No. 5,015,415, U.S. Pat. No. 5,034,218, U.S. Pat. No. 5,063,044, U.S. Pat. No. 4,902,499, U.S. Pat. No. 4,906,459, U.S. Pat. No. 5,554,313, U.S. Pat. No. 577,644) that focus on using silicone, and some specifically polysiloxanes, for various benefits to the hair. Such use levels have always been at concentrations below 50% wherein effectiveness for insect control was not evident. For actual effectiveness use in the range of 50-100% concentration is required.
[0025] It is believed that the lubricating properties of the silicone provide a morbidity passageway for interfering with insect respiratory and possibly digestive functions, and accordingly other similar lubricants and Silicone derivatives are effective in such insect control.
[0026] With regard to head lice, the point of entry where the silicone permeates the head lice is very likely the thoracic spiracle, the honeycomb structure which creates maximum surface area and efficient exchange of air and moisture. The nits are likely affected via the head louse nit operculum which contain doughnut shaped holes. See Meinking, T. L. Current Problems in Dermatology 11 (3) pp 73-120 May/June 1999.
[0027] With regard to head lice many natural oils treatments have been attempted but with limited efficacy. In a school based study to evaluate alternative treatments, children with head lice were treated with olive oil, mayonnaise, or Vasoline® petroleum jelly overnight under a shower cap. They came to school the next day with their greasy hair still covered by shower caps. After a shampoo rinse, the lice from heads treated with olive oil or mayonnaise were found to still be alive. The children who used Vasoline® had many dead nymphs stuck to the scalp or hair but some adult lice were still alive. See Meinking, T. L., ibid.
[0028] The efficacy of silicone based lubricants over other oils appears to be related to the lubricity of silicone. Silicone and more particularly Dimethylpolysiloxane (or Polydimethylsiloxane) has a far lower surface tension than other oils. Surface tension is a measure of the stretching force required to form a liquid film, and is equal to the surface energy of the liquid per unit length of the film at equilibrium: the force tends to minimize the area of a surface. Surface tension is caused by the attraction of molecules to each other.
[0029] Below is a list of the surface tension of a variety of polymers and oils at 20° C.
Polymer/oil system Surface Tension (dynes/cm) Polydimethylsiloxane (PDMS) 20.9 1 Polyisobutylene (PIB) 35.6 1 n-alkanes 37.8 1 n-fluoroalkanes 25.9 1 diesel fuel 25 2 deodorized sunflower oil 33 2 crude soybean oil 32 2 refined soybean oil 32 2 cottonseed oil 35.4 3 coconut oil 33.4 3 olive oil 33.0 3 corn oil 33.4 4 peanut oil 35.5 4 mineral oil (MWP paraffin) 28.8 4 mineral oil-baby oil 30.8 5 liquid paraffin 26-28 5 Krytox 1514 18 6
[0030] The surface tension of polydimethylsiloxane at about 20.9 dynes/cm is about 50% lower than the surface tension of most natural oils and is believed to account for its greater ability to penetrate and induce morbidity in insects. In our experiment with Krytox® 1514 a fluorinated oil PerFluoroPolyEther (PFPE), with a surface tension of 18, we found that it was also effective in killing lice but slightly less effective than Dow Coming 200 fluid, 350 CST . The greater effectiveness of the Dow Corning 350 CST material is very likely due to the its greater viscosity. Viscosity , or kinematic viscosity is measured in stokes, and is defined to be the dynamic viscosity divided by the density of the liquid; this gives a quantity which depends only on the type of the liquid. independent of its concentration or density. Krytox1514 has a viscosity of 142 centistokes (cst), while Dow Corning 200 fluid, 350 CST has a viscosity of 350 cst. The viscosity adds to the effectiveness by creating better adhesion of the lubricant to the insects.
[0031] Attempts have been made to modify vegetable oils thru processes such as transesterification in order to lower their surface tensions and thus make them usable as biodiesel fuels. See Cecil, A. W.; Allen, K.; Watts. C. and Ackman R. G. in “Predicting the Surface Tension of Biodiesel Fuels from Their Fatty Acid Composition”, JAOCS 76(3), pp. 317-323 (March ,1999). It is probable that if vegetable or other oils were processed to lower their surface tension close to the surface tension found in polydimethylsiloxane i.e. less than about 25 dynes/centimeter, it would have the same effect on the lice. | Described is a safe and effective method for treating lice and nits (fleas, ticks and other insects) with a low surface tension lubricant. | 0 |
This application claims the benefit of priority under 35 U.S.C. §119 of U.S. Provisional Application Ser. No. 61/522,956 filed on Aug. 12, 2011 the content of which is relied upon and incorporated herein by reference in its entirety.
BACKGROUND
1. Field
Embodiments relate generally to alkali-free glasses and more particularly to alkali-free, high strain point and/or intermediate expansion coefficient, fusion formable aluminosilicate, and/or boroaluminosilicate glasses which may be useful in photovoltaic applications, for example, thin film photovoltaic devices.
2. Technical Background
Substrate glasses for copper indium gallium diselenide (CIGS) photovoltaic modules typically contain Na 2 O, as diffusion of Na from the glass into the CIGS layer has been shown to result in significant improvement in module efficiency. However, due to the difficulty in controlling the amount of diffusing Na during the CIGS deposition/crystallization process, some manufacturers of these devices prefer to deposit a layer of a suitable Na compound, e.g. NaF, prior to CIGS deposition, in which case any alkali present in the substrate glass needs to be contained through the use of a barrier layer. Moreover, in the case of cadmium telluride (CdTe) photovoltaic modules, any Na contamination of the CdTe layer is deleterious to module efficiency and, therefore, typical Na-containing substrate glasses, e.g. soda-lime glass, require the presence of a barrier layer. Consequently, use of an alkali-free substrate glass for either CIGS, silicon, wafered crystalline silicon, or CdTe modules can obviate the need for a barrier layer.
SUMMARY
The intermediate thermal expansion coefficient and/or the alkali-free glasses disclosed herein are especially compatible with CdTe photovoltaic devices and may increase the efficiency of the cell.
One embodiment is a glass comprising, in mole percent:
55 to 75 percent SiO 2 ; 5 to 20 percent Al 2 O 3 ; 0 to 15 percent B 2 O 3 ; 0 to 10 percent MgO; 0 to 15 percent SrO; 0 to 16 percent CaO; and 0 to 9 percent BaO. wherein MgO+CaO+BaO+SrO is 13 to 20 percent, wherein the glass is substantially free of alkali metal, and wherein the glass has a liquidus viscosity of 100,000 poise or greater.
These glasses are advantageous materials to be used in copper indium gallium diselenide (CIGS) photovoltaic modules where the sodium required to optimize cell efficiency is not to be derived from the substrate glass but instead from a separate deposited layer consisting of a sodium containing material such as NaF. Current CIGS module substrates are typically made from soda-lime glass sheet that has been manufactured by the float process. However, use of higher strain point glass substrates can enable higher temperature CIGS processing, which is expected to translate into desirable improvements in cell efficiency.
Accordingly, the alkali-free glasses described herein can be characterized by strain points≧600° C. and thermal expansion coefficients in the range of from 35 to 50×10 −7 /° C., in order to minimize thermal expansion mismatch between the substrate and CIGS layer or to better match the thermal expansion of CdTe.
Finally, the preferred compositions of this disclosure have strain point well in excess of 650° C., thereby enabling CIGS or CdTe deposition/crystallization to be carried out at the highest possible processing temperature, resulting in additional efficiency gain.
Additional features and advantages will be set forth in the detailed description which follows, and in part will be readily apparent to those skilled in the art from the description or recognized by practicing the invention as described in the written description and claims hereof.
It is to be understood that both the foregoing general description and the following detailed description are merely exemplary of the invention, and are intended to provide an overview or framework for understanding the nature and character of the invention as it is claimed.
The accompanying drawing is included to provide a further understanding of the invention, and is incorporated in and constitutes a part of this specification. The drawing illustrates one or more embodiment(s) of the invention and together with the description serve to explain the principles and operation of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention can be understood from the following detailed description either alone or together with the accompanying drawing FIGURE.
FIG. 1 is a schematic of features of a photovoltaic device according to some embodiments.
DETAILED DESCRIPTION
Reference will now be made in detail to various embodiments of the invention.
As used herein, the term “substrate” can be used to describe either a substrate or a superstrate depending on the configuration of the photovoltaic cell. For example, the substrate is a superstrate, if when assembled into a photovoltaic cell, it is on the light incident side of a photovoltaic cell. The superstrate can provide protection for the photovoltaic materials from impact and environmental degradation while allowing transmission of the appropriate wavelengths of the solar spectrum. Further, multiple photovoltaic cells can be arranged into a photovoltaic module. Photovoltaic device can describe either a cell, a module, or both.
As used herein, the term “adjacent” can be defined as being in close proximity. Adjacent structures may or may not be in physical contact with each other. Adjacent structures can have other layers and/or structures disposed between them.
Moreover, where a range of numerical values is recited herein, comprising upper and lower values, unless otherwise stated in specific circumstances, the range is intended to include the endpoints thereof, and all integers and fractions within the range. It is not intended that the scope of the invention be limited to the specific values recited when defining a range. Further, when an amount, concentration, or other value or parameter is given as a range, one or more preferred ranges or a list of upper preferable values and lower preferable values, this is to be understood as specifically disclosing all ranges formed from any pair of any upper range limit or preferred value and any lower range limit or preferred value, regardless of whether such pairs are separately disclosed. Finally, when the term “about” is used in describing a value or an end-point of a range, the disclosure should be understood to include the specific value or end-point referred to.
As used herein, the term “about” means that amounts, sizes, formulations, parameters, and other quantities and characteristics are not and need not be exact, but may be approximate and/or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding off, measurement error and the like, and other factors known to those of skill in the art. In general, an amount, size, formulation, parameter or other quantity or characteristic is “about” or “approximate” whether or not expressly stated to be such.
The term “or”, as used herein, is inclusive; more specifically, the phrase “A or B” means “A, B, or both A and B”. Exclusive “or” is designated herein by terms such as “either A or B” and “one of A or B”, for example.
The indefinite articles “a” and “an” are employed to describe elements and components of the invention. The use of these articles means that one or at least one of these elements or components is present. Although these articles are conventionally employed to signify that the modified noun is a singular noun, as used herein the articles “a” and “an” also include the plural, unless otherwise stated in specific instances. Similarly, the definite article “the”, as used herein, also signifies that the modified noun may be singular or plural, again unless otherwise stated in specific instances.
It is noted that one or more of the claims may utilize the term “wherein” as a transitional phrase. For the purposes of defining the present invention, it is noted that this term is introduced in the claims as an open-ended transitional phrase that is used to introduce a recitation of a series of characteristics of the structure and should be interpreted in like manner as the more commonly used open-ended preamble term “comprising.”
As used herein, a glass composition having 0 wt % of a compound is defined as meaning that the compound, molecule, or element was not purposefully added to the composition, but the composition may still comprise the compound, typically in tramp or trace amounts. Similarly, “substantially free of alkali metal”, “substantially free of sodium”, “substantially free of potassium”, “sodium-free,” “alkali-free,” “potassium-free” or the like are defined to mean that the compound, molecule, or element was not purposefully added to the composition, but the composition may still comprise sodium, alkali, or potassium, but in approximately tramp or trace amounts. These tramp amounts are not intentionally included in the batch but may be present in minor amounts as impurities in the raw materials used to provide the major components of the glass.
One embodiment is a glass comprising, in mole percent:
55 to 75 percent SiO 2 ; 5 to 20 percent Al 2 O 3 ; 0 to 15 percent B 2 O 3 ; 0 to 10 percent MgO; 0 to 15 percent SrO; 0 to 16 percent CaO; and 0 to 9 percent BaO. wherein MgO+CaO+BaO+SrO is 13 to 20 percent, wherein the glass is substantially free of alkali metal, and wherein the glass has a liquidus viscosity of 100,000 poise or greater.
In one embodiment, the glass, comprises, in mole percent:
55 to 75 percent SiO 2 ; 5 to 13 percent Al 2 O 2 ; 0 to 15 percent B 2 O 3 ; 0 to 10 percent MgO; 0 to 15 percent SrO; 0 to 16 percent CaO; and 0 to 9 percent BaO.
In one embodiment, the glass, comprises, in mole percent:
55 to 75 percent SiO 2 ; 0 to 20 percent Al 2 O 2 ; 6 to 12 percent B 2 O 3 ; 0 to 10 percent MgO; 0 to 15 percent SrO; 0 to 16 percent CaO; and 0 to 9 percent BaO.
In one embodiment, the glass, comprises, in mole percent:
55 to 75 percent SiO 2 ; 5 to 13 percent Al 2 O 2 ; 6 to 12 percent B 2 O 3 ; 0 to 10 percent MgO; 0 to 15 percent SrO; 0 to 16 percent CaO; and 0 to 9 percent BaO.
In one embodiment, the glass, comprises, in mole percent:
55 to 75 percent SiO 2 ; 8 to 13 percent Al 2 O 3 ; 6 to 12 percent B 2 O 3 ; 0 to 7 percent MgO; 0 to 12 percent SrO; 0 to 16 percent CaO; and 0 to 9 percent BaO.
In one embodiment, the glass, comprises, in mole percent:
58 to 69 percent SiO 2 ; 8 to 13 percent Al 2 O 3 ; 6 to 12 percent B 2 O 3 ; 0 to 7 percent MgO; 0 to 12 percent SrO; 0 to 16 percent CaO; and 0 to 9 percent BaO.
In one embodiment, the glass, comprises, in mole percent:
73 to 75 percent SiO 2 ; 6 to 9 percent Al 2 O 3 ; 0 percent B 2 O 3 ; 1 to 3 percent MgO; 0 percent SrO; 13 to 16 percent CaO; and 1 to 3 percent BaO.
In one embodiment, the glass, comprises, in mole percent:
60 to 67 percent SiO 2 ; 8 to 12 percent Al 2 O 3 ; 6 to 12 percent B 2 O 3 ; 0.05 to 7 percent MgO; 0 to 12 percent SrO; 0.5 to 9 percent CaO; and 0.5 to 8 percent BaO.
The glass is substantially free of alkali metal, for example, the content of alkali can be 0.05 mole percent or less, for example, zero mole percent. The glass, according to some embodiments, is free of intentionally added alkali metal.
The glass is substantially free of sodium, for example, the content of sodium can be 0.05 mole percent or less, for example, zero mole percent. The glass, according to some embodiments, is free of intentionally added sodium.
The glass is substantially free of potassium, for example, the content of sodium can be 0.05 mole percent or less, for example, zero mole percent. The glass, according to some embodiments, is free of intentionally added potassium.
The glass is substantially free of sodium and potassium, for example, the content of sodium can be 0.05 mole percent or less, for example, zero mole percent. The glass, according to some embodiments, is free of intentionally added sodium and potassium.
In some embodiments, the glass comprises 55 to 75 percent SiO 2 , for example, 58 to 69 percent SiO 2 , or, for example, 60 to 67 percent SiO 2 , or, for example, 73 to 75 percent SiO 2 .
As mentioned above, the glasses, according some embodiments, comprise 0 to 15 percent B 2 O 3 , for example, 6 to 12 percent. B 2 O 3 is added to the glass to reduce melting temperature, to decrease liquidus temperature, to increase liquidus viscosity, and to improve mechanical durability relative to a glass containing no B 2 O 3 .
The glass, according to some embodiments, comprises MgO+CaO+BaO+SrO in an amount from 13 to 20 mole percent. MgO can be added to the glass to reduce melting temperature and to increase strain point. It can disadvantageously lower CTE relative to other alkaline earths (e.g., CaO, SrO, BaO), and so other adjustments may be made to keep the CTE within the desired range. Examples of suitable adjustments include increase SrO at the expense of CaO.
The glasses can comprise, in some embodiments, 0 to 15 mole percent SrO, for example, greater than zero to 15 mole percent, for example, 1 to 12 mole percent SrO. In certain embodiments, the glass contains no deliberately batched SrO, though it may of course be present as a contaminant in other batch materials. SrO contributes to higher coefficient of thermal expansion, and the relative proportion of SrO and CaO can be manipulated to improve liquidus temperature, and thus liquidus viscosity. SrO is not as effective as CaO or MgO for improving strain point, and replacing either of these with SrO tends to cause the melting temperature to increase. BaO has a similar effect coefficient of thermal expansion as SrO, if not a greater effect. BaO tends to lower melting temperature and lower liquidus temperature
The glasses, in some embodiments, comprise 0 to 16 mole percent CaO, for example, greater than 0 to 15 or, for example, 0 to 12 mole percent CaO, for example, 0.5 to 9 mole percent CaO. CaO contributes to higher strain point, lower density, and lower melting temperature.
The glass, according to one embodiment, further comprises 0 to 0.5 mole percent of a fining agent. The fining agent can be SnO 2 .
The glass, according to one embodiment, further comprising 0 to 2 mole percent of TiO 2 , MnO, ZnO, Nb 2 O 5 , Ta 2 O 5 , ZrO 2 , La 2 O 3 , Y 2 O 2 , P 2 O 5 , or a combination thereof. These optional components can be used to further tailor glass properties.
In some embodiments, the glass is substantially free of Sb 2 O 2 , As 2 O 2 , or combinations thereof, for example, the glass comprises 0.05 mole percent or less of Sb 2 O 2 or As 2 O 2 or a combination thereof. For example, the glass can comprise zero mole percent of Sb 2 O 2 or As 2 O 2 or a combination thereof.
Accordingly, in one embodiment, the glass has a strain point of 600° C. or greater, for example, 610° C. or greater, for example, 620° C. or greater, for example, 630° C. or greater, for example, 640° C. or greater, for example, 650° C. or greater. In some embodiments, the glass has a coefficient of thermal expansion of from 35×10 −7 /° C. to 50×10 −7 /° C., for example, 39×10 −7 /° C. to 50×10 −7 /° C. In one embodiment, the glass has a coefficient of thermal expansion of from 35×10 −7 /° C. to 50×10 −7 /° C. and a strain point of 600° C. or greater.
The glass can be fusion formed as known in the art of fusion forming glass. The fusion draw process uses an isopipe that has a channel for accepting molten glass raw material. The channel has weirs that are open at the top along the length of the channel on both sides of the channel. When the channel fills with molten material, the molten glass overflows the weirs. Due to gravity, the molten glass flows down the outside surfaces of the isopipe. These outside surfaces extend down and inwardly so that they join at an edge below the drawing tank. The two flowing glass surfaces join at this edge to fuse and form a single flowing sheet. The fusion draw method offers the advantage that, since the two glass films flowing over the channel fuse together, neither outside surface of the resulting glass sheet comes in contact with any part of the apparatus. Thus, the surface properties are not affected by such contact.
Glasses having a liquidus viscosity of greater than or equal to 100 kP, 100,000 poise, are usually fusion formable. Glass having a liquidus viscosity in the range of from 10 kP to less than 100 kP are usually float formable but not fusion formable. Some embodiments are alkali-free glasses with Tstr>630° C., α in the range of 4-5 ppm/° C., as well as liquidus viscosity (ηliq) in excess of 100,000 poise. As such, they are ideally suited for being formed into sheet by the fusion process. Moreover, many of these glasses also have a 200 poise temperature (T 200 ) that is well below 1550° C., making them ideal candidates for lower-cost versions of the fusion process.
In one embodiment, the glass is in the form of a sheet. The glass in the form of a sheet can be strengthened, for example, thermally tempered.
The glass, according to one embodiment, is optically transparent.
In one embodiment, as shown in FIG. 1 , a photovoltaic device 100 comprises the glass in the form of a sheet 10 . The photovoltaic device can comprise more than one of the glass sheets, for example, as a substrate and/or as a superstrate. In one embodiment, the photovoltaic device 100 comprises the glass sheet as a substrate or superstrate 10 or 18 , a conductive material 12 adjacent to the substrate, and an active photovoltaic medium 16 adjacent to the conductive material. In one embodiment, the device comprises two glass sheets, one as the superstrate and one as the substrate, having the compositions described herein. The functional layer can comprise copper indium gallium diselenide, amorphous silicon, crystalline silicon, one or more crystalline silicon wafers, cadmium telluride, or combinations thereof adjacent to the substrate or superstrate. In one embodiment, the active photovoltaic medium comprises a CIGS layer. In one embodiment, the active photovoltaic medium comprises a cadmium telluride (CdTe) layer. In one embodiment, the photovoltaic device comprises a functional layer comprising copper indium gallium diselenide or cadmium telluride. In one embodiment, the photovoltaic device the functional layer is copper indium gallium diselenide. In one embodiment, the functional layer is cadmium telluride.
The photovoltaic device 100 , according to one embodiment, further comprises one or more intermediate layer(s) 14 such as a sodium containing layer, for example, a layer comprising NaF or a barrier layer disposed between or adjacent to the superstrate or substrate and the functional layer. In one embodiment, the photovoltaic device further comprises a barrier layer disposed between or adjacent to the superstrate or substrate and a transparent conductive oxide (TCO) layer, wherein the TCO layer is disposed between or adjacent to the functional layer and the barrier layer. A TCO may be present in a photovoltaic device comprising a CdTe functional layer. In one embodiment, the barrier layer is disposed directly on the glass. In one embodiment, the device comprises multiple intermediate layers such as a sodium containing layer, for example, a layer comprising NaF, and an adjacent sodium metering layer located between the superstrate and the substrate.
In one embodiment, the glass sheet is optically transparent. In one embodiment, the glass sheet as the substrate and/or superstrate is optically transparent.
According to some embodiments, the glass sheet has a thickness of 4.0 mm or less, for example, 3.5 mm or less, for example, 3.2 mm or less, for example, 3.0 mm or less, for example, 2.5 mm or less, for example, 2.0 mm or less, for example, 1.9 mm or less, for example, 1.8 mm or less, for example, 1.5 mm or less, for example, 1.1 mm or less, for example, 0.5 mm to 2.0 mm, for example, 0.5 mm to 1.1 mm, for example, 0.7 mm to 1.1 mm. Although these are exemplary thicknesses, the glass sheet can have a thickness of any numerical value including decimal places in the range of from 0.1 mm up to and including 4.0 mm.
Alkali-free glasses are becoming increasingly attractive candidates for the superstrate, substrate of CdTe, CIGS modules, respectively. In the former case, alkali contamination of the CdTe and conductive oxide layers of the film stack is avoided. Moreover, process simplification arises from the elimination of the barrier layer (needed, e.g., in the case of conventional soda-lime glass). In the latter case, CIGS module manufacturers are better able to control the amount of Na needed to optimize absorber performance by depositing a separate Na-containing layer that, by virtue of its specified composition and thickness, results in more reproducible Na delivery to the CIGS layer.
EXAMPLES
Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, and Table 7 show exemplary glasses, according to embodiments of the invention. Properties data for some exemplary glasses are also shown in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, and Table 7. In the Tables T str (° C.) is the strain point which is the temperature when the viscosity is equal to 10 14.7 P as measured by beam bending or fiber elongation. α(10 −7 /° C.) in the Tables is the coefficient of thermal expansion (CTE) which is the amount of dimensional change from either 0 to 300° C. or 25 to 300° C. depending on the measurement. CTE is typically measured by dilatometry. ρ (g/cc) is the density which is measured with the Archimedes method (ASTM C693). T 200 (° C.) is the two-hundred Poise (P) temperature. This is the temperature when the viscosity of the melt is 200 P as measured by HTV (high temperature viscosity) measurement which uses concentric cylinder viscometry. T liq (° C.) is the liquidus temperature. This is the temperature where the first crystal is observed in a standard gradient boat liquidus measurement (ASTM C829-81). η liq is the liquidus viscosity expressed in kilopoise; thus 100 kP=100,000 P. This is the viscosity of the melt corresponding to the liquidus temperature.
TABLE 1
Example
Mole %
1
2
3
4
5
6
7
8
9
10
MgO
6.4
6.9
6.9
4.6
4.8
6.4
4.4
4.4
2.7
2.6
CaO
8.5
6.9
9.1
5.4
5.6
5.2
7.2
5.2
2.9
2.0
SrO
0
0
0
3.6
3.8
3.5
3.5
5.5
11.8
9.6
BaO
2.4
3.4
2.6
2.4
2.5
2.3
2.3
2.3
0.7
3.6
RO
17.2
17.2
18.6
16.0
16.7
17.4
17.4
17.4
18.0
17.7
B 2 O 3
10.0
10.0
10.8
10.7
11.2
10.3
10.3
10.3
9.0
7.5
Al 2 O 3
11.1
11.1
12.0
11.1
11.6
10.7
10.7
10.7
9.6
9.3
SiO 2
61.5
61.5
58.5
62.0
60.5
61.5
61.5
61.5
63.3
65.4
SnO 2
0.10
0.10
0.10
0.10
0.10
0.10
0.10
0.10
0.10
0.10
Tstr
645
642
641
643
641
642
641
642
645
649
α
41.8
40.6
41.5
40.7
41.2
40.0
41.0
41.9
46.2
46.5
ρ
2.53
2.56
2.56
2.57
2.59
2.58
2.58
2.62
2.70
2.75
T200
1473
1490
1515
Tliq
1060
1065
1050
1015
1020
1070
1040
1035
1130
1110
ηliq (kP)
205
777
459
TABLE 2
Example
Mole %
11
12
13
14
15
16
17
18
19
20
MgO
4.1
5.4
1.8
0
2.0
4.4
6.4
5.4
5.4
6.4
CaO
9.9
6.4
11.0
10.0
9.0
8.5
6.5
7.5
7.5
7.5
SrO
3.3
4.3
2.9
9.0
8.0
2.0
2.0
1.0
1.0
0
BaO
2.2
2.8
3.3
0
0
2.4
2.4
3.4
3.4
3.4
RO
19.4
19.0
19.0
19.0
19.0
17.3
17.3
17.3
17.3
17.3
B 2 O 3
9.7
10.7
10.7
8.0
8.0
10.0
10.0
10.0
9.0
9.0
Al 2 O 3
10.0
11.1
8.5
9.0
9.0
11.1
11.1
11.1
12.1
12.1
SiO 2
60.8
59.0
62.3
64.0
64.0
61.5
61.5
61.5
61.5
61.5
SnO 2
0.10
0.10
0.07
0.10
0.10
0.10
0.10
0.10
0.10
0.10
Tstr
639
636
631
648
649
650
645
650
659
661
α
46.5
43.9
46.0
48.4
45.8
40.4
41.4
39.5
40.3
39.8
ρ
2.70
2.64
2.67
2.63
2.57
2.60
2.56
2.60
2.58
T200
1423
Tliq
1045
1030
1075
1150
1145
1080
1080
1095
1080
1090
ηliq (kP)
192
TABLE 3
Example
Mole %
21
22
23
24
25
26
27
28
29
30
MgO
0.1
2.0
0
0
1.98
1.97
0.07
0.07
0.06
0.06
CaO
4.3
2.0
4.3
3.3
1.3
0.8
4.6
4.6
4.5
4.6
SrO
9.7
12.0
10.0
10.5
11.9
11.5
9.7
9.6
10.2
9.5
BaO
0.1
0.1
0.1
0.1
2.0
4.0
0.1
0.1
0.1
0.1
RO
14.1
16.1
14.4
13.9
17.2
18.3
14.4
14.4
14.8
14.2
B 2 O 3
8.4
6.6
8.5
8.5
6.4
6.4
9.9
11.4
9.9
11.5
Al 2 O 3
9.3
9.3
10.0
10.5
8.7
8.6
9.3
9.3
10.0
10.0
SiO 2
68.1
67.8
67.0
67.0
67.6
66.5
66.2
64.8
65.2
64.1
SnO 2
0.16
0.18
0.18
0.18
0.17
0.17
0.17
0.17
0.17
0.17
Tstr
668
674
668
673
667
665
658
649
659
656
α
40.9
42.8
41.7
41.8
45.9
46.6
42.1
42.5
42.3
42.4
ρ
2.59
2.65
2.59
2.59
2.72
2.77
2.58
2.58
2.59
2.59
T200
1595
1595
1594
1610
1563
1545
1569
1540
1555
1528
Tliq
1125
1125
1135
1150
1100
1075
1075
1070
1080
1080
ηliq (kP)
142
162
119
121
124
235
274
202
253
163
TABLE 4
Example
Mole %
31
32
33
34
35
36
37
38
MgO
4.7
2.5
3.5
4.5
3.8
3.9
4.2
4.4
CaO
5.6
7.0
5.5
4.5
6.0
5.7
5.6
5.5
SrO
3.7
1.5
2.0
2.0
2.2
2.5
2.9
3.3
BaO
2.5
7.0
7.0
7.0
7.6
6.2
4.9
3.7
RO
16.5
18.0
18.0
18.0
19.5
18.3
17.6
16.8
B 2 O 3
11.0
9.0
9.0
9.0
9.8
9.8
10.1
10.4
Al 2 O 3
11.4
9.0
9.0
9.0
9.8
9.9
10.3
10.8
SiO 2
61.0
63.9
63.9
63.9
60.9
62.0
62.0
62.0
SnO 2
0.10
0.10
0.10
0.10
0.10
0.10
0.10
0.10
Tstr
640
632
632
635
630
631
633
638
α
41.2
46.5
45.9
45.8
48.2
46.0
43.7
41.7
ρ
2.58
2.73
2.72
2.72
2.77
2.71
2.67
2.62
T200
1510
1490
1490
1494
1443
1475
1490
Tliq
1000
1050
1025
1020
1045
1000
1010
ηliq (kP)
893
166
364
437
106
756
808
TABLE 5
Example
Mole %
39
40
41
42
43
44
45
46
47
48
MgO
1.4
1.3
1.8
0.0
2.0
4.4
6.4
5.4
5.4
6.4
CaO
15.4
14.2
11.0
10.0
9.0
8.5
6.5
7.5
7.5
7.5
SrO
2.9
9.0
8.0
2.0
2.0
1.0
1.0
0
BaO
1.4
1.3
3.3
0
0
2.4
2.4
3.4
3.4
3.4
RO
18.1
16.7
19.0
19.0
19.0
17.3
17.3
17.3
17.3
17.3
B 2 O 3
10.7
8.0
8.0
10.0
10.0
10.0
9.0
9.0
Al 2 O 3
7.0
8.1
8.5
9.0
9.0
11.1
11.1
11.1
12.1
12.1
SiO 2
74.9
74.9
62.3
64.0
64.0
61.5
61.5
61.5
61.5
61.5
SnO 2
0.10
0.10
0.07
0.10
0.10
0.10
0.10
0.10
0.10
0.10
Tstr
735
745
613
648
649
650
645
650
659
661
α
42.7
40.6
46
48.4
45.8
40.4
41.4
39.5
40.3
39.8
ρ
2.67
2.67
2.63
2.57
2.60
2.56
2.60
2.58
T200
Tliq
1080
1080
1075
1150
1145
1080
1080
1095
1080
1090
ηliq (kP)
TABLE 6
Example
Mole %
49
50
51
52
53
54
55
56
57
MgO
0.1
2.0
0.0
0.0
2.0
2.0
0.1
0.1
0.1
CaO
4.3
2.0
4.3
3.3
1.3
0.8
4.6
4.6
4.5
SrO
9.7
12.0
10.0
10.5
11.9
11.5
9.7
9.6
10.2
BaO
0.1
0.1
0.1
0.1
2.0
4.0
0.1
0.1
0.1
RO
14.1
16.1
14.4
13.9
17.2
18.3
14.4
14.4
14.8
B 2 O 3
8.4
6.4
8.5
8.5
6.4
6.4
9.9
11.4
9.9
Al 2 O 3
9.3
9.3
10.0
10.5
8.6
8.6
9.3
9.3
9.9
SiO 2
68.1
67.8
67.0
66.9
67.6
66.5
66.2
64.8
65.2
SnO 2
0.16
0.18
0.18
0.18
0.17
0.17
0.17
0.17
0.17
Tstr
668
674
668
673
667
665
658
649
659
α
40.9
42.8
41.7
41.8
45.9
46.6
42.1
42.5
42.3
ρ
2.59
2.65
2.59
2.59
2.72
2.77
2.58
2.58
2.59
T200
1595
1595
1594
1610
1563
1545
1569
1540
1555
Tliq
1125
1125
1135
1150
1100
1075
1075
1070
1080
ηliq (kP)
142
162
119
121
124
235
274
202
253
TABLE 7
Example
Mole %
58
59
60
61
62
MgO
0.1
0.1
1.6
0.1
0.1
CaO
4.6
5.0
4.9
6.5
8.0
SrO
9.5
9.8
8.4
8.5
6.9
BaO
0.1
0.1
0.1
0.1
0.1
RO
14.2
15.0
15.0
15.1
15.1
B 2 O 3
11.5
10.4
10.3
10.3
10.4
Al 2 O 3
10.0
9.7
9.6
9.6
9.6
SiO 2
64.1
64.9
65.0
64.8
64.8
SnO 2
0.17
0.16
0.16
0.16
0.16
Tstr
656
655
653
657
656
α
42.4
42
41.8
42
42.5
ρ
2.59
2.60
2.56
2.57
2.55
T200
1528
1539
1546
1539
1536
Tliq
1080
1090
1100
1100
1080
ηliq (kP)
163
132
136
106
178
It will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the spirit or scope of the invention. Thus, it is intended that the present invention cover the modifications and variations of this invention provided they come within the scope of the appended claims and their equivalents. | A compositional range of high strain point and/or intermediate expansion coefficient alkali metal free aluminosilicate and boroaluminosilicate glasses are described herein. The glasses can be used as substrates or superstrates for photovoltaic devices, for example, thin film photovoltaic devices such as CdTe or CIGS photovoltaic devices or crystalline silicon wafer devices. These glasses can be characterized as having strain points≧600° C., thermal expansion coefficient of from 35 to 50×10 −7 /° C. | 2 |
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application claims the priority of German Patent Application, Serial No. 10 2011 051 115.6, filed Jun. 16, 2011, pursuant to 35 U.S.C. 119(a)-(d), the content of which is incorporated herein by reference in its entirety as if fully set forth herein.
BACKGROUND OF THE INVENTION
[0002] The present invention relates to a chassis structure for a motor vehicle.
[0003] The following discussion of related art is provided to assist the reader in understanding the advantages of the invention, and is not to be construed as an admission that this related art is prior art to this invention.
[0004] Constructional, technological and material lightweight solutions for weight reduction of chassis structures for motor vehicles gain increasingly importance with respect to reduction in fuel consumption and emission. Lightweight materials such as aluminum play a special role to reduce the so-called unsprung masses in the chassis area. This trend is further accelerated by the fact that low-emission or emission-free vehicles with hybrid or electric drive require added weight of about 130 kg to account for the required electric components. This weight has to be compensated through greater weight reduction of other components. To ensure the required high strength and stiffness properties of chassis structures, like pivot bearing, support arm, guide arm, A-arm etc., which are subject to high stress while still having a smallest possible own weight, chassis structures forged from aluminum with yield strength Rp0.2 of above 300 MPa and elongation at rupture A5 of above 10% are increasingly in demand. In addition to the yield strength as dimension criterion, chassis structures are also dimensioned for stiffness to withstand defined buckling loads in particular stress and crash situations. Crucial for the stiffness is the modulus of elasticity of the used material in addition to the cross section configuration. The modulus of elasticity of aluminum is about 70,000 kN/mm 2 which is three times smaller than that of steel. As a result, component regions that are critical with respect to stiffness encounter the undesired situation that the solid cross sections common in forged parts have to be increased to satisfy the demanded stiffness, causing additional mass and thus increased weight. As vehicles are built increasingly more compact also in the area of the chassis, space restrictions prohibit however a random increase of component cross sections in order to realize the required values for the stiffness-relevant section modulus of the component cross section, e.g. through use of lightweight hollow sections of greater diameter instead of massive cross sections.
[0005] As the stiffness-relevant modulus of elasticity of lightweight materials, like aluminum or other materials, can be influenced within very narrow limits only, known solutions propose the use of composites with materials of higher modulus of elasticity. For example, it is known to forge steel structures of varying geometric shape and thickness with a modulus of elasticity of about 210,000 kN/mm 2 onto stiffness-relevant regions of forged aluminum parts. Galvanic susceptibility to corrosion between galvanically relevant contact zones between aluminum base material and steel structure as well as corrosion of the steel surface itself has however been proven problematic. This is especially true when considering that such forged aluminum parts cannot be provided with an additional corrosion protection layer for cost reasons.
[0006] The use of various types of composites, e.g. composite of layers, particle composites, fiber composites etc., in shipbuilding, aircraft construction etc., have also been known which involve a layering of varying materials. These technologies are however unsuitable for cost reasons. A further known approach involves the use of metal matrix composites (MMC) which achieve a greater modulus of elasticity through incorporation of ceramic fibers in the aluminum matrix. High production costs for these metal matrix composites limit this technology to special applications and uses however. In particular known from Formula 1 motor racing are CFRP-based complete solutions which however are unsuitable for application in conventional automobile industry in view of their high costs and relatively brittle and deformation-resistant fracture behavior.
[0007] It would therefore be desirable and advantageous to provide an improved chassis structure to obviate prior art shortcomings.
SUMMARY OF THE INVENTION
[0008] According to one aspect of the present invention, a chassis structure for a motor vehicle includes a forged base body of light metal, a reinforcement body made of fiber material, and an adhesive layer connecting the base body and the reinforcement body by a force fit, wherein the base body has at least one region which is plastically deformed and partially encompasses the reinforcement body by a form fit.
[0009] The present invention resolves prior art problems by at least partially strengthening the forged light metal base body of a chassis structure with a reinforcement body of fiber material and connecting the base body and the reinforcement body by way of a force fit realized by an adhesive layer, and a form fit realized by a plastic deformation of at least one region of the base body to grip around the reinforcement body.
[0010] Advantageously, the reinforcement body is arranged in a stiffness-relevant section of the chassis structure or base body.
[0011] According to another advantageous feature of the present invention, the adhesive layer can be applied across an entire contact area between the base body and the reinforcement body. The reinforcement body may be made of carbon-fiber-reinforced plastic (CFRP).
[0012] According to another advantageous feature of the present invention, the adhesive layer can be made of a material on the basis of epoxy resin. The ratio of the modulus of elasticity of the material of the base body and the material of the reinforcement body is advantageously dimensioned between 1:3 and 1:7.
[0013] According to another advantageous feature of the present invention, the at least one plastically deformed region to form a connection between the components can extend at a marginal zone of the reinforcement body. The at least one plastically deformed region may in this case be configured in the form of a fold or be turned inwards.
[0014] According to another advantageous feature of the present invention, the base body can have at least one other region which extends through an opening in the reinforcement body and is plastically deformed. These types of connections can be configured in the form of rivets, with the plastically deformed region forming a closing head.
[0015] A chassis structure according to the present invention is characterized by the required stiffness and has defined portions to cope with buckling loads while yet complying with the given restrictions with respect to installation space in the absence of any increase in wall thickness to increase the section modulus of stiffness-relevant components, as has been proposed heretofore. A chassis structure according to the present invention exhibits only slight elastic deformation during normal operation when facing various stress situations while exhibiting high malleability in the event of abuse or crash to absorb energy through deformation and to maintain functional connections between individual chassis structures up to a define rupture in a controlled manner. The chassis structure is configured and the base body and reinforcement body interact such that no parts of the vehicle become loose and could pose a threat as uncontrolled flying objects when the breaking load is exceeded. This requirement is also designated as “fail safe behavior”.
[0016] Practice has shown that a chassis structure according to the present invention is especially beneficial when the preformed reinforcement body, preferably carbon shells (CFRP shells), is configured for a high modulus of elasticity, e.g. up to 380,000 MPa, i.e. five time greater than aluminum with about 70,000 kN/mm 2 , and permanently applied in a force-fitting and form-fitting manner onto respectively configured regions of the forged base body with partly higher stiffness requirements. The lasting connection involves a combination of force-fitting connection through adhesive application, advantageously an adhesive on the basis of epoxy resin, and a form-fitting connection through complete or partial folding of the edges of the reinforcement body and/or additional point or linear plastic deformation, e.g. riveting or crimping of particular regions of the base body with the reinforcement body. Through plastic deformation, partial regions of the base body are formed as connections from the material of the base body to formfittingly encompass or grip around the reinforcement body. The adhesive for implementing the force-fitting connection is applied across the surface at a particular thickness either on the joining side of the reinforcement body or the joining side of the light metal base body, while at the same time providing a compensation medium for any irregularities on the surfaces of the two components being joined. This ensures a force-fitting adhesive contact across the entire surface between reinforcement body and base body. Folding or crimping of the reinforcement body with the base body is made possible by forging the base body with a continuous or breached score line and linear elevations such as webs or sporadic elevations like hubs. The CFRP shell is placed upon the forging surface of the base body and held stably after application of the adhesive via the fold and/or matching openings and via the continuous or breached webs and/or nubs. Fold, webs, and nubs on the forged part as well as respective openings on the CFRP shell provide at the same time precise guiding and positioning aids for the CFRP shell on the base body. In a further operating cycle, the fold, webs, and nubs can be formed with a suitable tool, the fold are bent over, and the nubs pressed flatly or, depending on the configuration riveted or compressed so that the CFRP shell is pressed overall flatly onto the surface of the base body in a force-fitting manner by the adhesive layer and formfittingly connected by the plastically joined connection elements in the form of folds and rivets. As the CFRP shell is applied onto the stiffness-relevant surface zones of the base body, i.e. at maximum distance from the neutral lines, maximum stiffness effects with minimum CFRP material use, e.g. with minimum material thickness and respective weight reduction, can be realized in accordance with the physical dependence of the stiffness-relevant cross sectional moments of inertia from radius to neutral line in 3 rd power. The approach taken by the present invention may be expanded when for example two-point arms or rod arms used in great quantities have not only regions reinforced with CFRP but is realized in the form of a CFRP half-shell. One half of the base body is hereby configured as a typical forged part with two through-passages, and the other half of the base body is a CFRP half or CFRP half-shell which is also provided with through passages, just like the light-metal forged half, for receiving rubber bearings for example. The base body and the reinforcement body have thus corresponding openings. The parting plane of the forged half for receiving the CFRP half as CFRP reinforcement is provided with the afore-described form-fitting and force-fitting connections depending on the technical need at hand.
[0017] Compared to the state of the art which proposed to provide areas of higher stiffness basically only through increase of the cross section or wall thickness, i.e. ultimately weight increase, the approach taken by the present invention has the advantage that the union of ductile light metal material, advantageously aluminum, with highly rigid CFRP material, through use of the connections according to the present invention, is able to satisfy the need for reduced weight despite the seemingly contradictory demands on these structures, i.e. during normal operation the structures should exhibit only slight elastic deformations under most different stress situations, while exhibiting high malleability in the event of abuse and crash so as to absorb energy through deformation and to maintain functional connections between individual chassis structures up to a define rupture in a controlled manner. The additional stiffness functions are assumed by the reinforced section(s) or half-shell reinforcement body or bodies, in particular CFRP reinforcement(s), whereas the forged base body in its function as support element receives the reinforcement body in a lasting form-fitting and force-fitting connection in accordance with the present invention and provides the plastic deformation and energy absorption in the event of abuse or crash.
[0018] It will be understood by persons skilled in the art that one or more reinforcement bodies may be provided on one base body. Material selection, geometric arrangement and joining of base body and reinforcement body or bodies are suited to the desired stress behavior at hand. The demands on providing “fail safe behavior” can be satisfied with minimized weight, using the lasting material combination according to the present invention.
BRIEF DESCRIPTION OF THE DRAWING
[0019] Other features and advantages of the present invention will be more readily apparent upon reading the following description of currently preferred exemplified embodiments of the invention with reference to the accompanying drawing, in which:
[0020] FIG. 1 is a schematic illustration of a chassis structure according to the present invention in the form of a pivot bearing by way of example;
[0021] FIG. 2 is a sectional view of the chassis structure of FIG. 1 , taken along the line A-A;
[0022] FIG. 3 is a schematic illustration of a chassis structure according to the present invention in the form of a guide arm by way of example; and
[0023] FIG. 4 is a sectional view of the chassis structure of FIG. 1 , taken along the line B-B.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0024] Throughout all the figures, same or corresponding elements may generally be indicated by same reference numerals. These depicted embodiments are to be understood as illustrative of the invention and not as limiting in any way. It should also be understood that the figures are not necessarily to scale and that the embodiments are sometimes illustrated by graphic symbols, phantom lines, diagrammatic representations and fragmentary views. In certain instances, details which are not necessary for an understanding of the present invention or which render other details difficult to perceive may have been omitted.
[0025] Turning now to the drawing, and in particular to FIG. 1 , there is shown a schematic illustration of a chassis structure according to the present invention, generally designated by reference numeral 1 and configured in the form of a pivot bearing by way of example. The chassis structure 1 has a forged base body 2 of aluminum or aluminum alloy, which is joined with a shell-like reinforcement body 3 of carbon-fiber-reinforced plastic. The reinforcement body 3 is arranged in a stress-relevant leg portion 4 of the chassis structure 1 . The base body 2 and the reinforcement body 3 are connected with one another in a force-fitting and form-fitting manner. The force-fitting connection is implemented by an adhesive layer 5 ( FIG. 2 ) between the base body 2 and the reinforcement body 3 . The form-fitting connection is established by a plastic deformation of regions 6 , 7 of the base body 2 to partly encompass the reinforcement body 3 .
[0026] The adhesive layer 5 is made of an adhesive on the basis of epoxy resin and applied across the entire contact surface between the base body 2 and the reinforcement body 3 . The adhesive layer 5 provides also compensation of any unevenness in the joining surfaces between the base body 2 and the reinforcement body 3 .
[0027] The form-fitting connection between the base body 2 and the reinforcement body 3 is realized through plastic deformation of the regions 6 , 7 of the base body 2 . The regions 6 , 7 are formed during forging manufacture of the base body as webs 8 at the edge 9 of the base body 2 and as nubs 10 in the leg portion 4 . The reinforcement body 3 is provided with an opening 11 to form a rivet hole. The reinforcement body 3 is placed upon a receiving zone 12 of the base body 2 , with the adhesive layer 5 being interposed there between. The reinforcement body 3 is hereby placed with the opening 11 over the nub 10 and positioned between the webs 8 . Thereafter, the webs 8 and the nub 10 are plastically deformed so that the marginal webs 9 are turned inwards, and ends 13 of the nubs 10 are pressed flatly or compressed. During deformation, the opening 11 is filled by the material of the nub 10 . The plastically deformed regions 6 encompass the edge 14 of the reinforcement body 3 . The plastically deformed regions 7 form a closing head and grip the reinforcement body 3 around the opening 11 . The base body 2 and the reinforcement body 3 are then connected in a force-fitting and form-fitting manner.
[0028] FIG. 3 shows a schematic illustration of a chassis structure according to the present invention generally designated by reference numeral 15 and configured in the form of a guide arm by way of example. The chassis structure 15 is also formed by a forged base body 16 and a reinforcement body 17 . The base body 16 is made of light metal, in particular aluminum or aluminum alloy. The reinforcement body 17 is made of a fiber material, e.g. carbon-fiber-reinforced plastic. The base body 16 forms a structure half, and the reinforcement body 17 forms the other structure half.
[0029] The base body 16 and the reinforcement body 17 are connected with one another in a force-fitting manner by an adhesive layer 18 (cf. also FIG. 4 ) which is applied across the entire contact surface between the base body 16 and the reinforcement body 17 . Marginal regions 19 in the form of webs 20 and pin-like regions 21 in the form of nubs 22 of the base body 16 are plastically deformed and grip partially around the reinforcement body 17 . The pin-like regions 21 pass through openings 23 in the reinforcement body 17 , with the projecting ends 24 being plastically deformed to form a closing head. The marginal webs 20 are turned inwards by a plastic deformation and encompass the marginal regions 25 of the reinforcement body 17 .
[0030] The base body 16 and the reinforcement body 17 have corresponding openings 28 , 29 in the end portions 26 , 27 of the chassis structure 15 to establish through-passages for receiving rubber bearings 30 .
[0031] While the invention has been illustrated and described in connection with currently preferred embodiments shown and described in detail, 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 and scope of the present invention. The embodiments were chosen and described in order to explain the principles of the invention and practical application to thereby enable a person skilled in the art to best utilize the invention and various embodiments with various modifications as are suited to the particular use contemplated. | A chassis structure for a motor vehicle includes a forged base body of light metal and a reinforcement body made of fiber material. The base body and the reinforcement body are bought into forced engagement by an adhesive layer, wherein the base body has at least one first region which is plastically deformed and partially encompasses the reinforcement body by a form fit. | 1 |
TECHNICAL FIELD
[0001] The invention relates to a skin solution and related methods for preparing the same. With greater particularity the present invention relates to softening the skin and increasing the penetration of high molecular weight compounds at the site where the skin solution is applied.
BACKGROUND ART
[0002] Topical therapy permits drug application to a specific disease site in high concentrations with little systemic influence. This can yield an efficient dosage which minimizes the potential of side effects. Although little quantitative data are available on permeation of specific drugs, it is known that the percutaneous absorption of a drug varies greatly dependent on numerous factors. The principal barrier affecting permeation of drugs is the stratum corneum. Moreover, many cosmetic products are in ointment base or cream base, both of them have turned out to be excellent growth mediums for bacteria which provides undesirable and possible contamination of the skin.
[0003] Consequently, there is a need for a skin solution which is physically and chemical stable and is cosmetically acceptable to transport the active chemicals or drugs into the skin at the site where the skin solution is applied. There is also a need for a sprayable skin solution forming small droplets so that compounds with molasses consistency can be readily absorbed by the skin.
SUMMARY OF INVENTION
[0004] It is an object of the invention to provide a skin solution containing a natto extract to transport molecules with high molecular weight deep into the skin. The solution or composition will moisturize the dermis and thereby increase the penetration of said molecules at the site applied with the skin solution.
[0005] It is a further object of the invention to provide a skin solution which forms a barrier against moisture loss for a prolonged period of time after application and results in a higher liquid content retained by the cells.
[0006] It is a further object of the invention to provide a skin solution which softens and hydrates the superficial epidermal tissue if the tissue has become dry, cracked or impervious to penetration of drugs or chemicals. The composition will alter the membrane permeability of the skin and will soften any type of callus, corns, nail folds or dry skin in a few minutes and also facilitates the removal of said callus or dry skin.
[0007] It is a further object of the invention to provide a skin solution which will be physically and chemically stable and efficiently transport desired chemicals or drugs at the site on the skin applied with the skin solution.
[0008] It is a further object of the invention to provide a skin solution for treating dermal and mucosal disorders such as psoriasis, atopic dermatitis, pruritus, acne, rosacea, erithema and skin conditions associated with diabetes mellitus.
[0009] It is a further object of the invention to provide a skin solution which can kill bacterial, virus, germs or fungus on the site where the skin solution is applied.
[0010] It is a further object of the invention to provide a skin solution which is sprayable to form tiny droplets and can be readily absorbed by the skin. The delivery dosage could be measured per application.
[0011] It is a further object of the invention to provide a skin solution which is able to be a base liquid for a shampoo, conditioner, lotion or any other personal care product.
[0012] It is a further object of the invention to provide a method for preparing a stable aqueous composition containing a natto extract to transport molecules with high molecular weight deep into the skin. The composition will moisturize the dermis and thereby increase the penetration of said molecules to the site applied with the skin solution. For example, the composition should be stable for at least 6 months in a typical storage environment from 5 to 50 degrees Celsius.
[0013] It is a further object of the invention to provide a method for preparing stable aqueous composition by combining cleaning agent, ethoxylated castor oil derivatives and cationic quaternary ammonium salt to decompose the natto extract.
BRIEF DESCRIPTION OF THE FIGURE
[0014] FIG. 1 is a flow chart of the method steps of preparing the skin solution.
DETAILED DESCRIPTION OF INVENTION
[0015] A skin solution containing a natto extract, skin-softening agent, stabilizing agent, moisturizing agent, cleaning agent, ethoxylated castor oil derivatives and water-dispersible salt. The solution may contain an alcohol. Preferably, the skin solution transports molecules with high molecular weight deep into the dermis and increases the penetration of said molecules to the site applied with the skin solution. When the epidermal tissues become dry, cracked or impervious to penetration, the composition facilitates the action of said molecules across the skin to hydrate said epidermal tissues. The composition is able to soften the skin and to alter the membrane permeability of the skin.
[0016] In the described embodiments, disclosed are methods of preparing the skin solution containing natto extract, skin-softening agent, moisturizing agent, cationic quaternary ammonium salt, cleaning agent, ethanolamide derivatives, water-dispersible salt and alcohol.
[0017] The term “natto extract”, as used herein, is extracted from a traditional Japanese food called natto which is made from fermented soybeans by bacteria, such as Bacillus subtilis natto. The natto may be natto powder, for example, that available commercially. The natto extract is able to penetrate into the dermis and to carry the molecules with higher molecular weight across the skin barrier, to obtain the desired results. The natto contains nattokinase, prourokinase activator enzyme, fibrinolysis accelerating substances (FAS), vitamin K2, soybean, polyamine, spelmin, spelmigen daidzein, genistein, isoflavones, phytoestrogen and the chemical element selenium. The natto extract is selected from a group consisting of nattokinase, poly-g-glutamic acid, fibrinolysis accelerating substance, prourokinase activator enzyme and their mixture thereof. Alternatively, the natto extract is selected from a group consisting of fibrinolysis accelerating substance and prourokinase activator enzyme and mixtures thereof. Preferably, the concentration of the natto extract is from 0.5 to 2% by weight.
[0018] The said skin-softening agent is selected from a group consisting of one or more of natto extract, allantoin and di-isobutyl cresoxy ethoxy ethyl dimethyl benzyl ammonium chloride. Preferably, the concentration of the allantonin is present from 0.1 to 60% by weight and the concentration of di-isobutyl cresoxy ethoxy ethyl dimethyl benzyl ammonium chloride monohydrate is 0.001 to 0.5% by weight.
[0019] The stabilizing agent of the present invention is selected from a group consisting of one or more of allantoin and phenoxyethaol. The concentration of the phenoxyethanol in this specific embodiment is present from 0.001 to 0.5% by weight. The allantoin stabilizes the urea and prevents the same from decomposing in water to produce ammonia. Preferably, the concentration of the allantoin is present from 0.1 to 60% by weight. More preferably, the concentration of the allantoin is present at 0.5% by weight. The allantoin of the present invention also produces a whitening effect on the skin when applied topically.
[0020] The moisturizing agent of the present invention is selected from a group consisting of one or more of urea and natto extract. The concentration of the urea is present from 1% to 50% by weight and the concentration of the natto extract is 0.5 to 2% by weight.
[0021] The cleaning agent of the present invention is selected from a group consisting of one or more of nonylphenol ethoxylate, cocamido propyl betaine and castor oil ethoxylate. The concentration of the nonylphenol ethoxylate is from 0.001 to 2% by weight. Preferably, the concentration of the nonylphenol ethoxylate is from 0.0125 to 1% by weight, the concentration of the cocamido propyl betaina is from 0.001 to 5% by weight and the concentration of the ethoxylated castor oil is from 0.001 to 0.5% by weight.
[0022] The water-dispersible salt of the present invention is selected from a group consisting of one or more of chlorides, acetates, sulfates, nitrates, phosphates and organic salts. It is preferably a cationic quaternary ammonium salt, being selected from a group consisting of one or more of cocamido propyl betaina, di-isobutyl cresoxy ethoxy ethyl dimethyl benzyl ammonium chloride monohydrate, myristyl dimethylbenzene ammonium chloride, benzalkonium chloride, cetylpyridinium chloride, coconut dimethyl benzyl ammonium chloride, stearyl dimethyl benzyl ammonium chloride, alkyl dimethyl benzyl ammonium chloride, alkyl diethyl benzyl ammonium chloride, alkyl dimethyl benzyl ammonium bromide, di-isobutyl phenoxy ethoxy ethyl trimethyl ammonium chloride, di-isobutyl phenoxy ethoxy ethyl dimethyl alkyl ammonium chloride, methyl-dodecylbenzyl trimethyl ammonium chloride, cetyl trimethyl ammonium bromide, octadecyl dimethyl ethyl ammonium bromide, cetyl dimethyl ethyl ammonium bromide, octadecenyl-9-dimethyl ethyl ammonium bromide, dioctyl dimethyl ammonium chloride, dodecyl trimethyl ammonium chloride, octadecyl trimethyl ammonium chloride, octadecyl trimethyl ammonium bromide, hexadecynyl trimethyl ammonium iodine and octyltrimethyl ammonium fluoride. Preferably, the cationic quaternary ammonium salts are di-isobutyl cresoxy ethoxy ethyl dimethyl benzyl ammonium chloride monohydrate and cocamido propyl betaina; and the concentration of the cocamido propyl betaina is present from 0.001 to 5% by weight and the concentration of the di-isobutyl cresoxy ethoxy ethyl dimethyl benzyl ammonium chloride monohydrate is present from 0.001 to 0.5% by weight. More preferably, the concentration of the di-isobutyl cresoxy ethoxy ethyl dimethyl benzyl ammonium chloride monohydrate is present from 0.0025 to 0.2% by weight. Most preferably, the concentration of the di-isobutyl cresoxy ethoxy ethyl dimethyl benzyl ammonium chloride monohydrate is 0.15% by weight.
[0023] The quaternary ammonium salt is used to break the surface tension and permit the improved penetration of the natto extract into the site applied with the skin solution. There is a synergy when the cationic quaternary ammonium salt is used in combination with nonylphenol ethoxylate. The addition of nonylphenol ethoxylate provides a synergistic effect of greater penetration of the natto extract into the skin.
[0024] The ethoxylated castor oil derivative of the present invention are selected from a group consisting one or more of ethoxylated castor oil and undecylenamide DEA. The concentration of the undecylenamide DEA is present from 0.001 to 0.5% by weight and the concentration of the ethoxylated castor oil is from 0.001 to 0.5% by weight. Preferably, the concentration of ethoxylated castor oil is from 0.0125 to 1% by weight.
[0025] The skin solution of the present invention can also contain additives, preservatives, plant extracts, vitamins and their combinations thereof.
[0026] Examples of additives are azelaic acid, cozyme CQ10, biazulene, lecithin, ellagic acid, shea butter, dioxybenzone, avobenzone, zinc oxide, hyaluronic acid and their combinations thereof.
[0027] Examples of preservatives are methyl paraben, propyl paraben and their combinations thereof.
[0028] Examples of plant extract are tea tree extracts, pommergranate extract, aloe vera extract and their combinations thereof.
[0029] Examples of vitamins are vitamin a, vitamin c, vitamin e and their combinations thereof.
[0030] An example of alcohol is ethanol. The concentration of ethanol is 5% by volume.
[0031] The skin solution is in the form of a solution. Preferably, the composition is sprayable to form tiny droplets to be readily absorbed by the skin where the solution is applied. FIG. 1 is the flow chart of preparing the skin solution ( 10 ). The skin solution is prepared and mixed at ambient temperature. An amount of 1 to 600 grams of allantoin and 10 to 500 grams of urea is mixed with 1000 cc distilled water at ambient temperature until blended to form solution mixture A ( 100 ). An amount of 0.01 to 2 grams of nonylphenol ethoxylate, 0.01 to 2 grams of castor oil ethoxylate, 0.01 to 2 grams of undecylenamide DEA, 0.01 to 5 grams of di-isobutyl cresoxy ethoxy ethyl dimethyl benzyl ammonium chloride monohydrate, 0.01 to 5 grams of cocamidopropyl betaine and 0.01 to 5 grams of phenoxyethanol is mixed with 50 cc ethanol in a separate container at ambient temperature until blended to form the solution mixture B ( 105 ). The solution mixture B is combined with solution mixture A at ambient temperature until blended to form solution mixture C ( 110 ). An amount of 5 to 20 grams of natto powder is added into the solution mixture C and agitated for 4 to 6 hours at ambient temperature until the lumps completely dissolved to form solution mixture D ( 115 ). The solution mixture D is continuously agitated for 2 to 3 hours at ambient temperature ( 120 ) and followed by adding the defoamer into the solution mixture D and precipitate will be formed at ambient temperature. The end point of the reaction is reached when the pH reaches about 6.5. The precipitate is removed to form the product of skin solution ( 130 ).
[0032] In another embodiment, there is provided a topically applicable trans-dermal active component transport solution, comprising urea, urea stabilizing agent, natto extract, one or more ethoxylate entities and a cationic quaternary ammonium salt. Save where defined in this paragraph, the above text in relation to the skin solution is equally applicable to the transport solution. The ethoxylate entity is one or more of nonyl phenol ethoxylate, castor oil ethoxylate and undecylenamide DEA. The natto extract is selected from a group consisting of fibrinolysis accelerating substance, prourokinase activator enzyme and mixtures thereof. The transport solution may further comprise ethanol and cocamidopropyl betaina.
INDUSTRIAL APPLICABILITY
[0033] The present invention relates to a skin solution for transporting molecules with high molecular weight to the skin. More particularly, the present invention relates to a skin solution containing a natto extract and a method to prepare the same. | A skin solution for transporting molecules with high molecular weight to the skin, and/or moisturizing the epidermal tissues of the skin, and/or alternating the membrane permeability of the skin, and/or softening any type of callus, corns, nail folds or dry skin and facilitating the removal of the same. A method for preparing the skin solution, the solution being sprayable to form tiny droplets to be readily absorbed by the skin. | 0 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention is related to a new and useful plant care item in general and to a new apparatus which alternatively is useful as a watering apparatus or a sediment receiving apparatus.
2. Prior Art
One nearly universal vocation or avocation is the growth and care of potted plants whether of a hanging or other variety. These types of plants give a great deal of satisfaction to the growers thereof. For most growers, these plants provide a welcome relief to household chores and confinement. The plants tend to add color and excitement to many decors. However, these advantages are partly overcome or outweighed by the disadvantages encountered. That is, the difficulties in caring for such household plants, the watering and feeding thereof, can become a very unpleasant chore. In most cases, the household plants whether indoors or outdoors, whether potted or hanging, produce undesirable problems during the feeding and watering thereof. That is, in order to properly care for most plants it is essential to cause the soil in which the plant is rooted to be substantially saturated with water or other suitable fluid. To assure adequate watering or feeding is achieved, it frequently happens that excess water drips through the bottom of the pot or basket (or conversely overflows the pot or holder) thereby causing undesirable staining and/or making of the floor or surface therebeneath. These shortcomings can be extremely troublesome in areas where the surface or surface covering is expensive or of such a nature that it must be maintained at all times.
There are known kinds of apparatus which are used in conjunction with plants of the type described supra. Some of these kinds of apparatus are described in U.S. Patents discovered by applicant. The patents which appear to be most pertinent are: U.S. Pat. Nos. 608,590, G.A. Freund; 1,249,973, A.E. Lutey; and 951,684, J.E. Gillespie. However, the items covered by each of these patents is believed to have serious shortcomings.
SUMMARY OF THE INVENTION
This invention relates to apparatus useful in the care and feeding of household plants or the like. The basic apparatus comprises a step or tiered, substantially cylindrical receptacle which can receive flower pots or other plant holders of varying diameters. In addition the apparatus includes straps which may be used in suspending the apparatus from beneath a hanging pot or the like.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of the apparatus including the hanging straps.
FIG. 2 is a top view of the apparatus shown in FIG. 1 taken along the lines 2--2 of FIG. 1.
FIG. 3 is a cross-sectional view of the apparatus shown in FIG. 1 including a pot or similar plant receptacle from which the apparatus is suspended.
FIG. 4 is a cross-sectional view of the apparatus shown in FIG. 1 with the pots of different diameters shown therein.
DESCRIPTION OF PREFERRED EMBODIMENT
Referring now to FIG. 1, there is shown a perspective view of the apparatus of the instant invention. The apparatus 10 includes receptacle or pot-like arrangement 13 and a pair of straps 11 and 12 which are on the order of 10 inches long. Straps 11 and 12 include ends 11A and 11B as well as ends 12A and 12B, respectively. The receptacle and straps may be made of any suitable material such as a type of polypropylene, polystyrene, polyethylene, polyurethane or the like. The straps have relatively thin body portions (about 0.060 inch thick) and large end portions (about 0.100 inch thick) to provide additional strength and rigidity. Ends 11A, 12A and 11B and 12B are essentially identical whereby straps 11 and 12 are interchangeable and reversible end for end. In a typical application, the curved ends 11A and 12A of straps 11 and 12, respectively, are hooked over the edges of a flower post or hanging basket or the like. Ends 11B and 12B of straps 11 and 12, respectively, are hooked over the edges of receptacle 10 and inserted through aperture 111 (see FIG. 2) and aperture 112. Apertures 111 and 112 comprise slot-shaped apertures in ledge 15. Ledge 15 is a first step or ledge which is formed below the outer periphery or rim 14 receptacle 10. The width of ledge or shoulder 15 is not critical to the invention but should be sufficient to provide structural strength and area for supporting slots or apertures 111 and 112 therein. In addition, shoulder or ledge 15 can be sufficiently large to support a flower pot or the like when the straps 11 and 12 are removed for a free standing operation.
An additional ledge or shoulder 16 is formed below shoulder 15. Again, the width of ledge 16 is not critical to the invention but provides an additional ledge or shoulder for supporting a flower pot or the like of smaller dimension than is supported on the shoulder 15.
It is contemplated that additional ledges may be utilized depending upon the size of receptacle 10. However, an inordinate number of ledges would be impractical, non-utilitarian and expensive to produce.
A suitable trough 10 is produced by forming a recess in ledge 16 in the embodiment shown. Troughs 19 are useful to promote operation of the device as described hereinafter. A plurality of ribs 18 are formed in the angles between the bottom 17 and side wall 21 of receptacle 10. Side wall 21 extends between bottom 17 and ledge 16. In the embodiment shown, ribs 18 are relatively thick upright walls which extend from peripheral wall 21 towards the center of receptacle 10. In a preferred embodiment, rib 18 has a stepped configuration wherein support surfaces 18A and 18B are provided. In the embodiment shown, rib 18 extends only partially across the inner diameter of receptacle 10. It is contemplated that ribs 18 may be formed all the way across receptacle 10. In this arrangement, a pair of such ribs would form an X in the bottom of receptacle 10. However, the function thereof would not be changed from the function of ribs 18 as shown.
Referring now to FIG. 2, there is shown a top view of receptacle 10. In this figure as in other figures, common reference numerals apply to common components. In FIG. 2, straps 11 and 12 are shown hooked into the outer ledge or shoulder 15 of receptacle 10 as suggested in FIG. 1. Ledges 15 and 16 are shown and comprise concentric circular ledges. As noted supra, additional ledges may be provided depending upon the size of receptacle 10. Bottom 17 of receptacle 10 includes central portion 20 which may be raised as shown subsequently. Ribs 18 with shoulders 18A and 18B are indicated as relatively narrow, upright structures. As suggested supra, ribs 18 may be made thicker than suggested. In addition, ribs 18 may traverse the entire diametric dimension of the receptacle. In that case, only two ribs would be required rather than three. However, it is apparent that a three ribbed receptacle may be used in order to effect a reduction in materials required. Troughs 19 are shown in shoulder 16. The troughs extend virtually from upper wall 22 to lower wall 21. The troughs provide a run-off such as described herein.
Referring now to FIG. 3, there is shown one utilization of the instant invention. In this utilization, receptacle 10 is utilized in conjunction with a hanging basket or plant. A hanging planter or pot 50 is suspended from a suitable reference point (not shown) via hanging supports 55 which may be wires, chains, macrames or the like. Pot 50 is used to contain a suitable shrub or flower 53. Shrub 53 is potted in appropriate potting material or soil 57. In this embodiment, a suitable spout 54 which may represent a watering can or the like is used in supplying a suitable liquid 56 which may be water, nutrient or the like. When the appropriate amount of liquid has been applied, soil 57 becomes saturated and liquid begins to flow through aperture 57A at the bottom of the base of pot 50. This through-flow is represented by stream 51 which may include liquid, sediment and the like.
When receptacle 10 is utilized in a hanging basket fashion, straps 11 and 12 are hooked at ends 11A and 12A over the edge of pot 50. Ends 11B and 12B are inserted into apertures 111 and 112 in shoulder 15 to support receptacle 10. In this utilization, as the sludge in stream 51 flows from pot 50, it is collected in receptacle 19 which is suspended below pot 50. In a typical application, receptacle 10 is suffuciently large to receive all of this through-flow. By suspending receptacle 10 beneath the flower pot it is not essential for the person who is watering the plant to maintain careful control so as to avoid saturating the soil 57, to avoid overflow over the rim of pot 50, or to provide a basin or drip pan beneath pot 50.
When the watering operation is completed, receptacle 10 is merely detached from pot 50 either by removing ends 11A and 12A from the pot or ends 11B and 12B from receptacle 10 and discarding the residue in receptacle 10 in any suitable or appropriate manner. Receptacle 10 can then be replaced (or not) as dictated by the further requirements in regard to the appropriate pot.
Referring now to FIG. 4, there is shown another utilization of receptacle 10. In this utilization, pot 50 which contains plant 53 and soil 57 is seated directly on shoulder 16 of receptacle 10. Receptacle 10 is seated on any suitable surface such as surface 70. Again, as described in FIG. 5, liquid 56 is supplied via spout 54 until the run-off or sludge 51 passes through opening 50A at the bottom of pot 50. This run-off is collected as sludge 52 which may be disposed of in any suitable fashion.
Also shown in FIG. 4 is a smaller diameter pot 150 which is seated on shoulders 18B of ribs 18. The operation of receptacle 10 is identical. That is, run-off 51 will be accumulated as sludge 52 in the bottom of receptacle 10. This sludge may be disposed of in any suitable fashion. Of course, any other pot of any other suitable diameter can be arranged to rest upon on one or more of the ledges or shoulders in the receptacle. Thus, it is seen that the diameter of the pot supported by receptacle 10 can be quite small or quite large depending upon the ledge utilized for support.
It should be noted that in the event that a large diameter pot such as pot 50 is utilized troughs 19 are useful in providing a relief means such that the sludge may flow troughs 19 into the upper part of receptacle 10 thereby relieving pressure on the bottom of pot 50. In addition, troughs 19 permit evaporation of the liquid portion of sludge 52 in the bottom portion of receptacle 10 if the sludge is not immediately removed from the receptacle.
It should be noted that receptacle 10 has the additional utilization in the arrangement shown in FIG. 4 wherein receptacle 10 can be used as a soaker apparatus. That is, pot 50 can be seated in receptacle 10 and water or other liquid applied as shown by means of spout 54. In the case of shrubs such as ferns or the like which require extensive soaking, additional liquid can be applied to receptacle 10 and pot 50 may be permitted to sit in this liquid to absorb the liquid of the receptacle. In this case, troughs 19 permit ready access for the liquid to the bottom portion of receptacle 10 such that it can be absorbed through the bottom of pot 50.
Thus, there has been shown and described a preferred embodiment of improved horticultural apparatus. The embodiment shown includes a receptacle having plurality of shoulders or ledges for supporting pots of different sizes. The number of shoulders or ledges in not limitative of the invention and additional ledges may be inserted or withdrawn. While the material for fabricating the receptacle is not critical to the invention, preferred materials include any suitable plastic materials such as polypropylene, polystyrene, polyethylene, polyurathane or the like. Typically, the receptacle is about 0.100 inch thick. The height and diameter of the receptacle is variable depending upon the size of the pot to be accomodated and, consequently the amount of sludge or sediment which will be received from the pot. However, in one embodiment a height of 4 inches and a diameter of 10 inches has been utilized.
It is understood that those skilled in the art may conceive modifications to the instant invention. Any such modification are intended to be included within the purview of this description. This description is intended to be illustrative only and is not intended to be limitative of the invention. The scope of this invention is defined by the claims appended hereto. | An improved apparatus for use in caring for plants or horticultural items. The apparatus comprises a generally cylindrical member having stepped areas of varying diameter progressing from a large diameter to a small diameter wherein flower pots or the like of different diameters can be accomodated by the instant apparatus. In addition, the apparatus includes strap members or the like for hanging the apparatus from hanging baskets, pots or the like. The apparatus is useful as a catch basin or drip pan for receiving residue from a flower pot or the like during a watering process. Alternatively, the apparatus may be used as a watering pan for plants or the like which require prolonged soaking or watering. | 0 |
FIELD OF THE INVENTION
[0001] The present invention is relates to the field of fluid connectors. More specifically, the present invention is directed to a container connector which may be employed in automated chemistry systems
BACKGROUND OF THE INVENTION
[0002] Radiotracer synthesis has benefited from increased reliance on automated synthesizers and synthesis cassettes. Synthesis cassettes may be manufactured in a controlled environment and is shipped pre-assembled. For the end user this makes meeting GMP requirements simpler and radiotracer production more reliable than for platforms for which the cassette and reagents are supplied separately and are assembled by the end user. In this respect, minimizing the required number and complexity of connections made to the cassette prior to synthesis is desirable.
[0003] The FASTlab® system, sold by GE Healthcare of Liege, Belgium, is a synthesizer/cassette system which is able to perform multi-step radiochemistry and on-cassette cartridge based purification. Such processes may fully utilize the capacity of the FASTlab cassette and require additional reagent bottles to be connected thereto, especially for cartridge based purification where greater volumes of solvent are needed than can fit into the cassette casing. This has led to the use of additional reagent bottles that are connected to the cassette by piercing the bottle stopper with large diameter needles. Once the bottles stoppers are pierced by the needles, the reagent is available for use. It is not desirable to have the stoppers pre-pierced prior to shipping of a commercial cassette since the reagent is then not confined to the regent bottle and may contaminate the cassette or deform the bottle septum such that fluid integrity is lost. This prohibits shipping a fully assembled cassette and means that there must be some final assembly by the end user. The needle tops and tubing connections can be color-coded to simplify assembly by the end user but there is still potential for operator error which could lead to failed production. One such user error could be failing to push a needle into the bottom of the reagent bottle which would make the reagent inaccessible. Also, the use of needles results in the risk of stab injuries.
[0004] There is therefore a need for a means for connecting a conduit to a container in a manner that allows both to be shipped in an inactivated condition, that is, mechanically connected without establishing fluid communication therebetween, so as to then be placed in an activated condition the conduit and the container in fluid communication.
SUMMARY OF THE INVENTION
[0005] In view of the needs of the art, the present invention provides a connector cap for a reagent bottle which can be pre-attached to either a partially-assembled or a fully-assembled synthesis cassette. This will allow greater control in the assembly of the cassette and simpler operation for the end user. This type of reagent bottle should be particularly suited to delivery of volumes of solvent for on-cassette cartridge-based purification of radiotracers.
[0006] In an exemplary embodiment, the present invention provides a container connector for a container having an annular neck defining a container aperture and a pierceable septum spanning the container aperture. The container connector includes a connector cap and a septum piercing unit. The connector cap includes an annular cap body having opposed first and second ends and an elongate annular wall extending therebetween. The first end defines a first aperture, the annular wall includes an annular interior surface defining a cap cavity in fluid communication with the first aperture, and the interior surface is sized and shaped sized to engage the annular neck so that the cap can be moved from a first position with respect to the neck to a second position with respect to the neck. The septum piercing unit includes an elongate unit body including longitudinally opposed transversely-extending first and second end surfaces. The first and second end surfaces support a first cannula extending therefrom. The first cannula and unit body define a first and second fluid port respectively, wherein the first cannula and unit body further defines an elongate fluid passageway extending in fluid communication between the first and second fluid ports. The unit body is sized to span the container aperture such that the unit body is urgeable by the cap from the first position wherein the second cannula is positioned in overlying registry with the septum, to the second position wherein the second cannula has pierced the septum.
[0007] The reagent bottle can be pre-filled and attached to the cassette and is ‘activated’ by a simple operation by the end user prior to use. This should lead to fewer production failures due to incorrectly connected reagent bottles and safer operation due to reduced usage of sharp needles.
[0008] The connector cap may also be mated to bottles or vials providing sources of other fluids, or to a bottle or vial used for product collection or dispensing.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] FIG. 1 depicts an exploded view of a bottle incorporating a container connector of the present invention.
[0010] FIG. 2 depicts a cap and septum-piercing unit of the present invention.
[0011] FIG. 3 depicts a cross-sectional view of the container connector in a first position, before ‘activation’
[0012] FIG. 4 depicts a cross-sectional view of the container connector in a second position, after ‘activation’
[0013] FIG. 5 depicts an automated synthesis cassette incorporating a container connector of the present invention between the cassette and a reagent container.
[0014] FIG. 6 depicts a support member which may be employed with a container connector of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0015] The present invention provides a connector cap for allowing quick connection between a conduit and a container. The present invention also provides a container, such as a bottle or vial, configured to engage or incorporate the connector cap of the present invention. The connector cap of the present invention allows:
i) additional reagent to be used with a fully pre-assembled automated synthesis cassette; ii) simplified operation by the end user with reduced chances of production failure; iii) maintaining integrity of a reagent container until ‘activation’ before use; iv) connection to be made without exposing the operator to sharp needles; and v) other applications where connection between a container and a fluid conduit are required, including, e.g., source vials and or product collection vials.
[0021] The bottle body has a threaded top and a septum which keeps the reagent contained within the cavity until ‘activation’. The septum piercing unit is pushed downwards by the action of tightening the cap. The cap has an open top to allow access to the fittings on the septum piercing unit. The septum is pierced by the two spikes (or needles or cannulas, etc.) on the septum piercing unit. This constitutes ‘activation’. Before activation the reagent is sealed with the bottle cavity. After activation the reagent is accessible and may be provided through the septum piercing unit to, e.g., a FASTlab cassette. The bottle includes dip tube which makes sealing connection with fluid cannula, or needle, of the piercing unit so as to effect deeper penetration of the fluid cannula into the bottle cavity.
[0022] Desirably, the piercing unit and the bottle cooperatively engage each other so as to prevent rotation of the piercing unit by the rotation of the cap. Additionally, the dip tube may be fluted at one end to allow for some rotational displacement of the fluid cannula, the septum being contemplated to assist in the fluid-tight connection between the cannula and dip tube.
[0023] Similarly, the piercing unit provides a vent cannula which pierces the septum to thus allow for airflow into the bottle cavity and assist in evacuation of the reagent through the fluid cannula. The bottle may include a vent tube which, like the dip tube for the fluid cannula, provides sealed engagement with the vent cannula. The present invention further contemplates that both the dip tube and the vent tube may depend from a planar substrate supported below the septum in the bottle.
[0024] The reagent bottle might be constructed mainly from polypropylene which would have compatibility with water/organic mixtures. Other materials could be considered. Glass is also a possible material for the main bottle body.
[0025] Referring now to FIG. 1 , an exploded view of a reagent bottle 5 defining an open container cavity 6 employing a container connector 10 of the present invention is shown. Container connector 10 includes a connector cap 12 and a septum piercing unit 14 which cooperatively engage bottle 5 . Bottle 5 includes an annular neck 16 supporting a pierceable elastomeric septum 18 spanning across an open container aperture 20 defined by neck 16 . Septum is desirably formed from an elastomeric material which may be pierced by either a needle or cannula but will self-seal up removal of the needle or cannula for applications requiring the contents within cavity 6 to remain after removal of the needle or cannula. Bottle 5 includes a concave bottom 9 facing cavity 6 so as to provide a ‘low point’ within cavity 6 in which fluid will collect when bottle 5 is upright.
[0026] With additional reference to FIGS. 2-4 , connector cap 12 includes an annular cap body 22 having opposed first and second ends 24 and 26 and an elongate annular wall 28 extending therebetween. First end 24 includes an inwardly-extending annular rim 25 which defines a first aperture 30 . Annular wall 28 includes an annular interior surface 32 defining a cap cavity 34 in fluid communication with first aperture 30 . Interior surface 32 is sized and shaped sized to engage the annular neck 16 so that the cap can be moved from a first position with respect to the neck to a second position with respect to the neck. Septum piercing unit 14 includes an elongate unit body 40 including longitudinally opposed transversely-extending first and second end surfaces 42 and 44 . The first and second end surfaces 42 and 44 support first cannula 46 extending therefrom. First cannula 46 and unit body 40 define a first and second fluid port, 50 and 52 , respectively and an elongate fluid passageway 54 extending in fluid communication between first and second fluid ports 50 and 52 . Unit body 40 is sized to span container aperture 20 so that second end surface 44 is engaged by rim 25 such that unit body 40 is urgeable by cap 12 from the first position, depicted in FIG. 3 , wherein the first cannula 46 is positioned in overlying registry with septum 18 , to the second position, depicted in FIG. 4 , wherein second cannula 46 has pierced septum 18 .
[0027] Unit body 40 of said septum piercing unit 14 may be configured to include opposing first and second major surfaces 54 and 56 , respectively, which extend in facing opposition to interior surface 32 as container connector 10 is assembled. Septum piercing unit 14 may further include an elongate hollow needle 60 extending through unit body 40 thereof, where needle 60 includes a first end 62 , a second end 64 , and an elongate tubular body 66 extending therebetween. First end 62 defines a first needle aperture 68 , second end 64 defines a second needle aperture 70 , and tubular body 66 defines an elongate needle passageway 72 extending in fluid communication therebetween, such that said first end 62 of needle 60 is first cannula 46 which pierces septum 18 . Second end 64 of needle 60 supports a connector 74 thereon, such as a female luer connector. As depicted in the example shown in FIG. 5 , connector 74 engages a mating connector at one end of an elongate conduit 75 having an elongate tubular body defining an open conduit passageway therethrough. Connector 74 is thus able to place the conduit passageway in fluid communication with needle passageway 72 . The present invention contemplates that conduit 75 may be connected to a synthesis cassette 100 as shown in FIG. 5 , or to any source of a fluid to deliver to container 5 .
[0028] While first cannula 46 is depicted as being the first end 62 of needle 60 , the present invention further contemplates that cannula 46 may be formed from as a unitary member with unit body 40 . Additionally, first cannula 46 may have either a sharp or blunt first end for piercing septum 18 . It is known that blunt cannulas may be designed to pierce septums. As some embodiments of the present invention will not be concerned with the integrity of septum 18 after fluid withdrawal from cavity 6 , it will be apparent to those of ordinary skill in the art how to thus select the design of cannula 46 for the particular application.
[0029] The present invention further contemplates that container connector 10 further includes an elongate second cannula 48 projecting from unit body 40 . Second cannula 48 provides for piercing septum 18 for venting. In the embodiment shown in FIG. 1-4 , a vent needle 80 extending through unit body 40 provides both the second cannula 48 as well as the vent passageway through unit body 40 . Vent needle 80 includes a first end 82 , a second end 84 , and an elongate tubular vent body 86 extending therebetween. First end 82 defines a first vent aperture 88 , second end 84 defines a second vent aperture 90 , and tubular body 86 defines an elongate vent passageway 92 extending in fluid communication therebetween. The present invention contemplates that vent needle 80 provides the second cannula 48 . Desirably, vent body 86 supports a porous filtration media 94 across second aperture 90 . Media 94 defines porous passageways 96 therethrough in fluid communication with vent passageway 92 so as to limit the passage of contaminants therethrough but still allows air to vent therethrough from container 5 . As unit body 40 is urgeable by cap 12 from the first position wherein the second cannula 48 is positioned in overlying registry with septum 18 , to the second position wherein second cannula 48 has pierced septum 18 . The present invention further contemplates that filtration media 94 may be supported within any housing such that the filter passageways 96 are in sealed fluid communication with vent passageway 92 . For example, as shown in FIG. 5 , vent needle 80 may include provide a media housing 81 suspended above cap 12 such that vent body 86 includes bend to accommodate the particular geometry of housing 81 about other components or connections of container connector 10 .
[0030] The present invention contemplates that cap 12 and neck 16 include mating helical threads 13 and 17 , respectively, which guide movement of the cap between the first and second positions. Desirably, cap 12 and neck 16 further include cooperating detents for resisting movement of cap 12 from the first position. Additionally, cap 12 and neck 16 desirably include cooperating detents for resisting movement of cap 16 from the second position.
[0031] Additionally still, septum piercing unit 14 engages neck 16 so as to prevent rotation of the septum piercing unit along its axis of travel as cap 16 is moved from the first to the second position. Towards this goal, that neck 16 may provide opposing guide slots 21 and 23 into which opposing edges 41 and 43 of planar unit body 40 are received so as to allow the linear displacement towards septum 18 , although any mating engagement between unit body 40 and neck 16 will be configured to allow such linear displacement. For example, should unit body 40 have substantially cylindrical shape, neck 16 could support one or more inwardly-extending rails which are received in corresponding grooves formed in unit body 40 .
[0032] The present invention further contemplates providing an elongate tubular dip tube 102 supported in bottle cavity 6 for use with container connector 10 . Dip tube 102 includes a first end 104 , an opposed second end 106 , and an elongate tubular dip tube body 108 extending therebetween. First end 104 defines a first dip tube aperture 110 , second end of dip tube 102 defines a second dip tube aperture 112 , and dip tube body 108 defines an elongate dip tube passageway 114 extending in fluid communication therebetween. Desirably, second end 106 of dip tube 102 is positioned adjacent septum 18 in underlying registry with the first end 62 of needle 60 . First end 104 of dip tube 102 extends towards the bottom of cavity 6 , desirably centered above the concave bottom 9 . The present invention contemplates that when cap 12 is moved to the second position, first end 62 of needle 60 will be in fluid-tight engagement with first end 104 of dip tube 102 , as that portion of septum 18 about needle 60 will be compressed therebetween, while still placing dip tube passageway 114 in fluid communication with needle passageway 72 . In one embodiment of the present invention shown in FIG. 6 , a dip tube support member 120 positions second end 106 of dip tube 102 adjacent to septum 18 . Dip tube support member 120 spans container aperture 20 , and is desirably held in place between an annular container shoulder 7 and septum 18 . Support member 120 includes an outer annular ring 122 with a segment 124 extending to support second end 106 of dip tube 102 . Annular ring 122 is sized and shaped to rest on an annular shoulder 7 of container 5 . Septum 18 sealingly engages interior surface 32 while adjacent to or on rim 122 Support member 120 may be designed so as to hold second end 106 of dip tube either abutting against septum 18 or slightly spaced thereabove. As the tip of needle 60 is pushed through septum 18 into dip tube 102 , the material of septum 18 can serve as a gasket between needle 60 and dip tube 102 so as to ensure fluid from to or from needle 60 all passes out of or in through dip tube 102 at aperture 110 . The present invention further contemplates that annular ring 122 of support member 120 may take other shapes such as substantially planar or substantially conical where the second end 106 of dip tube 120 opens therethrough.
[0033] Moreover, the present invention contemplates alternatively providing an elongate tubular vent tube 130 supported by support member 120 in bottle cavity 6 . Vent tube 130 including a first end 132 , an opposed second end 134 , and an elongate tubular vent tube body 136 extending therebetween. First end 132 defines a first vent tube aperture 138 , second end 134 defines a second vent tube aperture 140 and vent tube body 136 defines an elongate vent tube passageway 142 extending in fluid communication therebetween. As second end 134 is positioned adjacent septum 18 in underlying registry with first end 82 of vent needle 80 , vent tube 130 is able to receive the first end of vent needle 80 as it is inserted through septum 18 upon movement of cap 12 to the second position. In the second position, passageway 92 is placed in fluid communication with vent tube passageway 142 . Fluid delivered through needle 60 into cavity 6 will cause the gas within cavity 6 to be pushed out through vent needle passageway 92 . Similarly, as fluid is withdrawn from cavity 6 through dip tube 102 and needle 60 , gas may be reintroduced into cavity 6 through vent tube passageway 142 .
[0034] As described, the provision of dip tube 102 and vent tube 130 allows for a fluid to be delivered into cavity 6 without requiring deep penetration of needle 60 or vent needle 80 through septum 18 . Additionally, if needle 60 and dip tube 102 sealingly-engage each other as described, the contents of cavity 6 may also be withdrawn therefrom. The present invention thus provides for a container to which fluid may be delivered and withdrawn, providing for the possibility of mixing a fluid to the contents of the container, such as a reagent provided within cavity 6 , so that the mixture may be withdrawn from the container.
[0035] The present invention further contemplates that both the dip tube and the vent tube may be supported below the septum in the bottle. With additional reference to FIG. 6 , support member 120 may then include segment 126 inwardly extending from rim 122 to second end 134 of vent tube 130 . Again, it may be desirable to provide some clearance between second aperture 140 and septum 18 so as to allow some deflection of septum 18 towards the first openings of the dip tube and vent tube as the cannulas are urged through the septum.
[0036] As shown in FIG. 1 , the present invention may alternatively include a removable key 200 which prevents unintended movement of cap 12 and septum piercing unit 14 . Key 200 includes opposed deflecting tangs 201 and 202 which define a neck receptacle 204 therebetween. Key 200 includes a grip 205 for ease of pulling key 200 laterally away from neck 16 . Key 200 may be positioned such that neck 16 is received in neck receptacle 204 with tangs 201 and 202 extending between cap 12 and bottle 5 . Tangs 201 and 202 prevent cap 12 from being tightened down on neck 16 until key 200 is removed from about neck 16 . Key 200 thus prevents unintended movement of cap 12 which could pre-maturely pierce septum 18 .
[0037] Further enhancements to the design could include the provision of some kind of rip off tab which would prevent accidental activation prior to use. This could be similar in design to those seen commonly on food containers. There could also be some kind of locking mechanism whereby once the bottle has been activated, it cannot be un-activated. This could be similar in operation to the mechanism commonly used on medicine bottles.
[0038] Referring now to FIG. 5 , the present invention also contemplates providing a synthesis cassette 100 incorporating the container connector 10 of the present invention. Cassette 100 is a version of a FASTlab synthesis cassette, although the present invention contemplates that the present invention can be applied to the cassettes for other synthesizers. Cassette 100 includes an elongate manifold 302 which incorporates a number of actuation valves 301 - 325 which are connected to either an activity inlet reservoir 330 , syringe pumps 332 , 334 , 336 , cartridges 340 , 342 , conduits 350 and 352 leading to a reaction chamber 326 , or conduits 354 and 356 leading to cartridges 340 and 342 respectively. Valves 308 , 309 , 317 and 320 are capped so as to provide connection to nothing. Manifold 300 is further connectable to a waste vial (not shown), a dispense vial (not shown), as well as to internal reagent vials (at valves 302 , 312 - 314 and 316 , not shown). The actual design of cassette 100 is not essential to the present invention, so long as it provides most or all of the fluid path used for the synthesis of a product fluid, such as a radiotracer for PET or SPECT imaging and so long as it provides for connection to a container connector 10 of the present invention. An active isotope is provided to an inlet reservoir at valve 306 and operation of the cassette may then direct it through a synthesis procedure. Valve 315 is connected to a source 360 of water for injection. Manifold 300 further provides ports for connection to a pneumatic system to further provide a motive force through manifold 300 .
[0039] Using container connector 10 , the cassette 100 may be shipped connected to an external reagent bottle 5 having a neck 16 , as described hereinabove, which cooperatively engages the cap 12 of connector 10 and the septum piercing unit 14 . The present provides that cassette 100 may be shipped with the connections made between reagent bottle 5 and cassette 100 with connector cap 12 in the first, inactivated, position. Key 200 is provided about neck 16 so as to prevent cap 12 from inadvertently causing unit body 40 from piercing septum 18 . Alternatively, the present invention provides a kit of parts including a cassette 100 and reagent vial 5 adapted to be connected to cassette 100 by connector cap 10 and conduit 75 . The kit of parts may be shipped in a sterile package, such as a plastic bag, allowing the kit components to be loaded into the sterile package in environmentally clean conditions where the container is then sealed so as to maintain the clean or sterile condition experienced by the kit components until the package is opened. It is contemplated that the package is opened in a clean environment so that the kit components may be assembled and put to use without requiring further sterilization. Cassette 100 when assembled, may then be connected to an automated synthesizer, in the present illustration a FASTlab synthesizer, as well as connected to a waste vial, a dispense vial, and optionally to an HPLC purification system (shown at valves 318 and 319 ). Cassette 100 may thus be operated to include a reagent included within vial 5 in the synthesis process it performs. The actual synthesis process is not considered essential to the instant invention, just the provision of an external reagent bottle 5 which may be connected to manifold 300 either a time just prior to synthesis or even just prior to packaging.
[0040] While the particular embodiment of the present invention has been shown and described, it will be obvious to those skilled in the art that changes and modifications may be made without departing from the teachings of the invention. The matter set forth in the foregoing description and accompanying drawings is offered by way of illustration only and not as a limitation. The actual scope of the invention is intended to be defined in the following claims when viewed in their proper perspective based on the prior art. | A connector cap for a reagent bottle which can be pre-attached to a fully assembled synthesis cassette allows greater control in the assembly of the cassette and simpler operation for the end user. The connector cap may be incorporated onto reagent bottle or on vials to be used with automated synthesis cassettes. | 1 |
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent application Ser. No. 12/681,309 filed on May 26, 2010, which is a national phase application of International Patent Application No. PCT/FR2008/001375 filed on Oct. 2, 2008, which claims priority to French Patent Application No. FR 07 06927 filed on Oct. 3, 2007, the disclosures of which are hereby incorporated by reference in their entireties.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to a portable apparatus for the treatment and/or shaping of hair employing means for generating steam, possibly in conjunction with a shaping device provided for untangling, styling, or setting hair in connection with steam.
[0004] 2. Description of Related Art
[0005] Apparatuses for the steam treatment of hair are known to the prior art, such as disclosed in U.S. Pat. No. 5,263,501, in which the apparatus is a curling iron consisting of a housing bearing a mandrel having a conical base fastened to the housing and projecting to form a cylindrical tip section equipped with peripheral steam outlet openings. The conical base receives the steam from a generator associated with the housing, and the steam then follows the longitudinal axis of the mandrel towards the outlet openings thereof. The cylindrical section is inserted in a curler on which the hair is wound and then steam treated in that state. A disadvantage resides in this apparatus in that the steam transfer takes place remotely from the steam outlet opening of the generator, which results in load losses and hence a diminished steam outflow. Furthermore, such an arrangement of the steam outlet remotely from the generator also leads to condensation. As a result, aside from the reduced steam yield, a return pipe must be provided to the tank, which in turn complicates the construction of the apparatus. Furthermore, because the water is supplied to the tank inside the generator by means of a hand pump, the steam chamber is often flooded, particularly when the person using the apparatus and wanting a greater steam flow presses the pump trigger too often. This results not only in a very irregular steam flow but also water discharges, which are annoying and even hazardous to the person using the apparatus.
[0006] To remedy these disadvantages, the document WO 2004/002262 describes a solution in which the apparatus is a flat iron consisting of two jaws that are elastically jointed at one of their ends. According to this document, the steam generating means form a sandwich structure, which is contained in one of the jaws. More particularly, one jaw has a tank for the treatment liquid, which impregnates a lock placed in contact with the heating element of the jaw for vaporizing said liquid, which then passes through openings provided for this purpose in the treatment surface designed to contact the hair. Although this device generates a more stable steam flow than the apparatus of the preceding document, the main disadvantage of this apparatus resides in the fact that, in spite of its rather complicated structure, it only generates a very weak steam flow, notably less than 2 g/min. A treatment performed with such a steam flow does not produce any observable effects on the hair, which must then be subjected to a supplementary, rather powerful heat treatment in order to give it a certain style, and of which the very high temperature dries out the hair and may damage it.
[0007] The object of the present invention is to remedy, at least partially, these disadvantages and to propose a hair shaping apparatus capable of delivering a continuous, uniform supply of steam suitable for a thorough and effective hair treatment, which also possesses a simple construction and is safe to operate.
[0008] Another object of the invention is a hair treatment apparatus designed for rapidly delivering a regulated supply of steam to the hair being treated, which can also be disconnected from a possible supplementary source of heat and/or mechanical tensioning and/or chemicals.
[0009] Another object of the invention is a steam hair shaping apparatus which is reliable in operation, which is designed to avoid condensation, and which can be manufactured easily and economically.
SUMMARY OF THE INVENTION
[0010] These objects are achieved with a portable steam hair treatment apparatus comprising a housing consisting of a liquid tank, means for supplying liquid to a steam generator comprising a vaporization chamber in thermal contact with an electric heating element, the vaporization chamber communicating with one or a plurality of openings for dispensing the steam to a lock of hair, wherein the generator is supplied with liquid by an electric pump and wherein the flow rate of the steam provided is greater than 5 g/min, and preferably in a range of between 10 g/min and 60 g/min.
[0011] Such a steam generator fed by an electric pump makes it possible to supply a significant flow of steam quickly, uniformly, and continuously to the lock of hair being treated, hence resulting in a durable and thorough treatment of the latter. By using an electric pump in which the maximum flow supplied is advantageously calculated as a function of the maximum heating power of the vaporization chamber, the liquid introduced into the chamber by the pump is immediately and completely turned into steam, thus preventing a discharge of non-vaporized liquid droplets from the dispensing openings. Furthermore, such an apparatus is portable, thus enabling the steam outlet to be arranged as closely as possible to the steam generation elements of the housing in order to eliminate condensation, while simplifying the construction of the apparatus and making it easier to manipulate.
[0012] In performing laboratory tests with a steam flow greater than 5 g/min and capable of going as high 100 g/min on locks of hair, either in the natural state or coated with cosmetics, it was observed that the effect of the treatment was clearly visible on the treated lock, as the hair had already been well prepared for a subsequent treatment by a strong steam flow, which had, for example, cleaned and uniformly moisturized it. This effect persisted even on locks subsequently treated with a hair shaping device employing a mechanical action and/or heat, because the hair that had already been moisturized in a more controlled manner retained its shaping for a longer time, with remarkable results in terms of its appearance, particularly sheen and color, which were uniform throughout.
[0013] By performing the same tests on several types of locks, it was observed that the flow range of between 10 g/min and 60 g/min gave the best results in terms of opening scales and moisturizing the hair for most of the hair types analyzed.
[0014] Advantageously, the dispensing opening or openings are arranged on one of the ends of the housing of the apparatus, and the latter comprises a deflector oppositely arranged, relative to the dispensing opening or openings.
[0015] This deflector functions as a steam shield by being oppositely positioned relative to the steam outlet, while leaving a space to accommodate a lock of hair. On one hand, this deflector makes it possible to protect to the scalp of the person receiving the treatment and on the other hand, to redirect the steam to the back of the lock and thus treat it on both of its sides with a steam outlet located on only one of its sides.
[0016] Preference is given to the power of the electric heating element being in the range of between 600 W and 1000 W.
[0017] This makes it possible to increase the temperature in the vaporization chamber rapidly to around 150° C. for vaporizing, preferably instantaneously, the liquid introduced into the chamber by the pump.
[0018] Advantageously, the steam generator consists of a bottom plate equipped with a liquid intake opening and at least one outlet opening for the steam generated, and of a top plate, wherein the steam is made to circulate between the two plates by at least one baffle circuits having a length in the range of between 100 mm and 200 mm.
[0019] Such baffle circuits make it possible to increase the contact time and to vary the displacement direction of the liquid in contact with the hot wall of the generator and to improve appreciably the heat transfer during boiling. The vaporization chamber is thus superheated, and all of the water droplets carried by the flow are vaporized before they reach the steam outlet openings of the chamber.
[0020] Preference is given to the apparatus comprising one or a plurality of pipes connecting the outlet of the vaporization chamber to the dispensing opening or openings, wherein each pipe is less than 3 cm long.
[0021] The vaporization chamber is thus positioned as closely as possible to the steam dispensing or outlet openings, hence making it possible to steam treat the lock of hair directly from the outlet of the vaporization chamber via one or a plurality of pipes. As these steam pipes exiting the vaporization chamber are very short in length, they dispense the steam in such a way that condensates cannot form, which could otherwise interfere with and/or cancel the action of the steam on the lock or impair the utility of the apparatus, as the condensates in a worst case scenario could burn the person who is using the apparatus or is receiving the treatment.
[0022] Advantageously, the apparatus has a control device for regulating the flow rate of liquid supplied to the generator.
[0023] Such a device for regulating the flow rate of liquid supplied by the pump to the vaporization chamber makes it possible to adapt the flow rate of the steam generated according to the type of treatment and/or to the type of hair being treated with the apparatus.
[0024] In a preferred embodiment of the invention, the apparatus has a hair shaping device comprising at least one treatment surface generally elongate in shape and coming into contact with a lock of hair, and said steam dispensing openings are adjacent to the hair shaping device.
[0025] A hair shaping device is understood to mean a device designed to come into contact with hair, at least temporarily and/or locally, in order to untangle it, style it or simply keep it in contact with a treatment surface such as, for example: a comb, a cylinder impregnated with a hairstyling product, such as a coloring agent, a flat iron with jointed mobile or fixed arms, a curling iron with a cylindrical heating mandrel possibly cooperating with at least one heating plate oppositely arranged relative thereto, a straightening head comprising a plurality of parallel treatment surfaces arranged side by side, etc.
[0026] The direction of the hair shaping is generally defined by the generally elongate treatment surface of the hair shaping device, a surface that generally treats the width of a lock with its longest side. By arrangement of the dispensing openings in the vicinity of the edge of the hair shaping device, the steam is prevented from reaching the interior of the device, thus effectively separating the steam treatment function from another hair shaping function such as, for example, a treatment involving the application of heat and/or tension or pressure to the hair, and/or a hairstyling product such as a fixation agent, etc., for an improved result on the lock being treated.
[0027] Advantageously, the steam path is defined via a plurality of openings uniformly distributed parallel to the treatment surface of the hair shaping device, which aim the steam in a direction perpendicular to that of their hair shaping by said device.
[0028] A steam path arriving perpendicular to the width of a lock of hair hence enables a quick and moreover, a homogeneous treatment of the lock when the steam is dispensed by outlet openings covering the width of the lock.
[0029] In a first alternate embodiment of the invention, the dispensing openings are adjacent to the hair shaping device and disposed upstream relative thereto.
[0030] “Upstream” is understood to mean that, in the treatment operation, a portion of the lock of hair first undergoes the steam application before undergoing the shaping treatment.
[0031] Tests performed by treating a lock of hair with steam emitted upstream of the hair shaping device have shown that the steam opens the scales of the hair and thoroughly cleans it. The mechanical action subsequently exerted by the hair shaping device rids the hair of any remaining impurities, such as those from an earlier treatment and/or care process.
[0032] The laboratory tests also showed that the steam emitted upstream of the hair shaping device, when the latter comprises a cosmetic dispensing system, enhances the penetration of said cosmetic into the interior of the hair, thus improving the deep-penetrating action of said cosmetic.
[0033] It has also been observed that treating the lock of hair with a device exerting a thermal action in addition to the mechanical action after the steam application keeps the hair from drying out, as the hair is pre-coated with a layer of moisture. Obviously this layer is vaporized during the styling process, but it, rather than the water contained in the core of the hair, is vaporized, thus protecting the hair from any desiccation linked to the application of a hot hair shaping device.
[0034] Lastly, the laboratory tests also showed that the steam emitted upstream of the hair shaping device sufficiently moisturizes the hair, thus protecting it from significant desiccation during the action of the hair shaping device, which may be heated to a high temperature, for example, 230° C.
[0035] In a second alternate embodiment of the invention, said dispensing openings are adjacent to the hair shaping device and disposed downstream thereof.
[0036] “Downstream” is understood to mean that, in the treatment operation, a portion of the lock of hair first undergoes the shaping treatment before undergoing the steam application.
[0037] Tests performed with an apparatus configured according to this variant of the invention have shown that, after a mechanical shaping of the lock, the steam remoisturizes the hair to compensate for the desiccation linked to the application of the hot treatment surface of a shaping device on the hair.
[0038] Preference is given to the hair shaping device comprising at least one electric heating element in thermal contact with the treatment surface.
[0039] Such a device comprising its own heating element independent from that of the steam generator enables the achievement of a durable hair shaping, for example a straightening, curling, or crimping. When steam is applied to a lock of hair after it has been shaped by a device exerting a thermal action, even in combination with a mechanical action on the lock, the steam remoisturizes the hair in order to compensate for the desiccation linked to the application of a hot instrument to the hair.
[0040] Preference is given to the hair shaping device having controls independent from those for the steam.
[0041] This makes it possible to separate the two functions, hence enabling the operating parameters for each function to be adjusted independently.
[0042] Advantageously, the housing comprises a body that extends downwards to form a handle, wherein the hair shaping device is oppositely arranged relative to the handle and the steam path exiting from the dispensing openings is aligned along the longitudinal axis of the body of the housing.
[0043] Such a configuration of the housing ensures both ergonomic use and effective treatment of the hair by the steam.
[0044] In a preferred embodiment of the invention, the hair shaping device has two jointed arms displaceable in opposite directions and in each case having a hair treatment surface, wherein at least one of the arms has a heating element in thermal contact with said treatment surface.
[0045] Such a device ensures an effective, long-lasting straightening of the hair.
[0046] Advantageously, the hair shaping device is detachable from the housing of the apparatus.
[0047] This constitutes a simple and economical means for enabling the apparatus to be used with the same hair shaping device or even with a plurality of hair shaping devices by either a right-handed or a left-handed person.
[0048] This also makes it possible to apply steam alone, without shaping beforehand or afterwards. In this case, the steam shield is integrated with the body of the apparatus and not with the hair shaping device.
[0049] Preference is given to the liquid in the tank being a treatment product.
[0050] Treatment liquid is understood to mean any liquid capable of being vaporized by the generator and then capable of being applied to the hair in vapor form for care, shaping, colorization, de-colorization, etc. This liquid is water in a preferred embodiment of the invention.
[0051] In another embodiment of the invention, the apparatus has a supplementary liquid tank adjacent to or associated with the hair shaping device.
[0052] This supplementary tank may thus be associated with either the apparatus or the hair shaping device and it allows a liquid that is not necessarily vaporized by the steam generator of the apparatus to be applied to the hair, for example, during an application in which the liquid from the supplementary tank is brought into contact with the treated lock.
[0053] Advantageously, the liquid contained in the supplementary tank is different from the liquid contained in the tank for supplying the steam generator.
[0054] This makes it possible to apply a cosmetic liquid, such as a hairstyling or colorization agent, in addition to the steam treatment.
[0055] Hence, in the case wherein the cosmetic was applied prior to the steam application, the steam serves as a transport medium for the cosmetic, enabling it to penetrate to the core of the hair via the opening of the scales, wherein the subsequent mechanical treatment closes the scales again and performs a type of cauterization of the hair to fix the cosmetic.
[0056] Furthermore, in the case wherein the cosmetic was applied after the mechanical and thermal treatment of the hair, the steam is used as a transport medium, thus protecting the cosmetic from exposure to very high temperatures and from thermal degradation.
BRIEF DESCRIPTION OF THE DRAWING(S)
[0057] The invention will become more clear by studying a special embodiment of the invention and its variants, which are in no way limiting and which are illustrated in the appended figures, wherein:
[0058] FIG. 1 is a perspective view of a portable apparatus for the steam treatment of hair according to a special embodiment of the invention comprising a hair shaping device illustrated in the closed position;
[0059] FIG. 2 is a perspective view of the apparatus of FIG. 1 , with the hair shaping device in the open position;
[0060] FIG. 3 a is a perspective view of the apparatus of FIG. 1 without the hair shaping device, the housing and the cover of the vaporization chamber having been removed from the apparatus;
[0061] FIG. 3 b is a magnified view of a detail of FIG. 3 a;
[0062] FIG. 4 is a perspective view of a hair shaping device of the apparatus of FIGS. 1 and 2 ; and
[0063] FIG. 5 is a perspective view of the apparatus for the steam treatment of hair according to a variant of the embodiment of the apparatus of FIG. 1 .
DESCRIPTION OF THE INVENTION
[0064] The appended figures, except for FIG. 4 , illustrate a portable apparatus for the steam treatment of hair consisting of a plastic housing 1 comprising a body 2 with a downwardly projecting extension forming a handle 3 receiving a detachable water tank 4 of which the top wall forms the top part of the handle. The extension of the housing 1 also contains means for supplying power 6 ( FIG. 3 a ) to a steam generator 8 contained in the body 2 of the housing 1 . The steam generator 8 consists of a chamber 10 for, e.g., instantaneous vaporization associated with an electric heating element 9 ; said elements are visible in FIG. 3 a.
[0065] According to the invention, the steam generator is supplied by an electric pump and is configured in such a way as to be able to generate a steam flow greater than 5 g/min, with preference being given to a range of between 10 g/min and 60 g/min.
[0066] The supply means 6 in particular comprise an electric pump 5 , which can be seen in FIG. 3 a and which is started by a control switch 7 . The circuit connecting the electric pump 5 to the tank 4 and to the generator 8 can also be discerned in FIG. 3 a . The electric pump 5 hence has an inlet opening 16 connected by a first pipe 17 to the tank 4 and a discharge opening 18 directing the water coming from the tank 4 through a circuit supplying the steam generator 8 . More particularly, the circuit supplying the steam generator 8 has a second pipe 19 leading to a junction dividing the supply circuit into a first pipe branch 20 connected to an inlet opening 21 in the vaporization chamber 10 of the steam generator 8 and a second pipe branch 22 connected to the tank 4 and allowing a portion of the water coming from the pump 5 to be piped to the tank 4 . The passage of the first pipe branch 20 is smaller than that of the second pipe branch 22 , the latter being made of a flexible hose, the apparatus further comprising a mechanism 23 for controlling the flow of the water piped into the generator 8 . The control mechanism 23 comprises means for compressing the flexible hose of the second pipe branch 22 , which passes through a cylindrical housing 25 . More particularly, by turning a knurled knob 24 the control mechanism 23 actuates a toggle lever inside the housing 25 , which lever presses on the outer surface of the flexible hose.
[0067] When the pump 5 is started by the control switch 7 , it sucks the water from the tank 4 via the first pipe 17 and pipes the water via the second pipe 19 , the water flow conducted by this circuit thus being divided into a first, weak flow piped to the generator 8 and a stronger flow piped to the tank. The flow of water to the generator 8 can be increased by turning the knob 24 to compress the return hose to the tank 4 .
[0068] More particularly according to the invention and as can be discerned more clearly in FIG. 3 b , the vaporization chamber 10 comprises an enclosed compartment formed between a bottom plate 50 of a general rectangular shape and a top plate (not shown for the sake of greater clarity), wherein the two plates are fastened together on their four corners by screws 52 . A silicone gasket 51 disposed between the two plates ensures that the inside of the vaporization chamber 10 is sealed.
[0069] The bottom plate 50 is equipped with a plurality of raised sections forming baffles, which ensure that the fluid is directed from a water inlet to the steam outlet openings of the chamber. Water enters the vaporization chamber 10 via the inlet opening 21 located in the middle of a front wall 53 . The flow of the incoming water is divided, then the droplets of water and steam are directed by the raised sections of the bottom plate 50 along the two symmetrical, labyrinthine paths 55 and 56 , which are arranged on either side of the axis of the chamber passing through the central inlet opening 21 . Each of the paths 55 , 56 has a length of ca. 150 mm for increasing the heating zone of the chamber, in order to turn the water entering the vaporization chamber 10 into steam. The two paths 55 , 56 rejoin each other in a buffer zone 57 located right in front of a back wall 54 of the chamber. The buffer zone 57 forms a dispensing chamber for the steam exiting via the openings 58 . In the illustrated example, there are five openings 58 in the back wall 54 that lead to five pipes 14 via five inner nozzles integrally formed with the chamber as a single component. Each pipe 14 is fastened in a leak-proof manner at one of its ends to the outlet of a nozzle and has on its opposite end a spray jet aligned with a dispensing opening 12 of the housing of the apparatus. In addition, the inner walls of the vaporization chamber 10 are covered with a layer formed from a granular coating, which is designed to increase the contact surface between the walls and the water droplets inside the chamber and thus improve the diffusion of the droplets on the heating surface of the chamber. Such a vaporization chamber is capable of instantaneously generating dry steam from the outlet.
[0070] The steam generator 8 is constructed from an aluminum or aluminum alloy block possessing good thermal inertia qualities and forming a calorie reservoir for the vaporization chamber 10 , enabling rapid vaporization of the water when the pump is turned on. The vaporization chamber 10 and the electric heating element 9 form a monoblock unit. In the example illustrated in the figures, the electric heating element 9 is a 900 W armored resistor. Electrical power is supplied to the apparatus via an electric cord 15 , and the power supply to the heating element 9 is controlled by an on/off switch on the apparatus.
[0071] The water flowing into the vaporization chamber 10 is rapidly turned into steam by the latter as it flows along the path of the baffles of said instantaneous vaporization chamber 10 . The steam exits the vaporization chamber 10 via a plurality of openings formed in a back wall of said vaporization chamber opposite the wall accommodating the inlet opening 21 . Each of the steam outlet openings of the vaporization chamber 10 communicates with a pipe 14 for dispensing the steam outside the apparatus. In FIG. 3 b it is hence possible to discern five short pipes 14 , each of which is, for example, ca. 1 cm long, enabling the steam to be dispensed immediately after exiting the vaporization chamber 10 .
[0072] As can be discerned more clearly in FIG. 2 , the bottom part of the body 2 of the housing 1 on the side opposite the handle 3 is closed by a flat side 11 having a plurality of steam dispensing openings 12 , each of which openings communicates with the outlet of a pipe 14 .
[0073] According to an advantageous aspect of the invention, the steam dispensing openings 12 are adjacent to a hair shaping device 30 . Hence the top part of the body 2 advantageously accommodates the hair shaping device 30 , the latter having at least one treatment surface 31 located in the extension parallel to, even set back a few millimeters from, the flat side 11 of the housing 1 .
[0074] The hair-setting device 30 can be more easily discerned in FIG. 4 and it consists of two arms 33 , 34 joint-mounted about a hinge 35 and held in an open position, or in a closed position in a variant, by a compression spring (not shown in the drawings). It is hence possible to discern a top arm 33 having, on its free end, a flared insertion shoe 36 that extends to form a flat, rectangular treatment surface 31 in contact with a heating element. On its free end, the bottom arm 34 likewise has a flared insertion shoe 37 that extends to form a flat, rectangular treatment surface 32 in contact with a heating element.
[0075] Each treatment surface 31 , 32 is constituted by a metal plate that makes thermal contact with an electric heating element (not shown in the drawings), which can be a resistance, CTP, infrared, etc. heating element and which is positioned against the treatment surface and inside the plastic bodies 38 and 39 , respectively, of each arm 33 , 34 . Each electric heating element can have its own control mechanism and is supplied with power by an electric cord 40 . Provision is made of the heating element for heating the plates to temperatures ranging from 90° C. to 230° C. In a variant, the apparatus has a single electric cord 15 for supplying electricity to the steam generator 8 and to the heating plates of the hair shaping device 30 . The treatment surface 31 , 32 is made of a heat conducting material and may be polished, coated with an enamel, a ceramic material, a layer of glass, etc.
[0076] The arms 33 , 34 are hence elastically mobile and capable of pivoting about an axis perpendicular to the longitudinal axis of their respective treatment surfaces 31 , 32 between an open and a closed position. Hence a lock of hair can be inserted between the treatment surfaces 31 , 32 of the arms 33 , 34 when the arms are in the open position, and the lock can then be subjected to pressure in order to bring, it into contact with said treatment surfaces 31 , 32 when the arms are in the closed position, which closing is possible by pressing on the outer surface of the bodies 38 , 39 of the arms. The flat treatment surfaces 31 , 32 thus straighten the lock with which they come into contact.
[0077] In an alternate embodiment of the hair shaping device 30 , the jaws are closed at rest and it is necessary to introduce the lock manually between the treatment surfaces 31 , 32 by stretching it out and then pushing it between the two plates with the aid of the insertion shoes 36 , 37 . Advantageously, a control mechanism for opening the plates wide enough so that the lock can be more easily inserted is conceivable, wherein said mechanism could be actuated, for example, from the handle or in the vicinity of the handle of the apparatus.
[0078] According to an advantageous aspect of the invention, the bottom arm 34 comprises a deflector 42 consisting of a wall 43 arranged set back from, but parallel to the treatment surface 32 . The wall 43 forms a steam shield that protects the scalp from the action of the steam while diverting the steam towards the lock being treated. Another advantage of diverting the steam in this manner is that the front and the back of the lock can be impregnated with steam from a steam outlet arranged on just one side.
[0079] According to another advantageous aspect of the invention, the top arm 33 has a mounting bracket 45 on the body 2 of the housing 1 of the apparatus, more particularly a fastener that can be detached by means of a screw 46 cooperating with a threaded borehole in the top part of the body 2 of the apparatus. This detachable fastener makes it possible, by unscrewing the screw 46 , to switch from a positioning that is suitable for use by a right-handed person, as shown in the figures, to another positioning wherein the device is rotated 180° about the longitudinal axis of the body 2 for enabling a left-handed person to use the apparatus. This hair shaping device can be replaced by another device, such as one comprising a cylindrical curling element cooperating with a pivoting fastening clip for the hair, with this device then being inserted in the mounting bracket 45 and attached to the body 2 of the housing 1 of the apparatus. The detachable fastener for the hair shaping device 30 also makes it possible to use the steam treatment apparatus alone, without a hair shaping device attached to its steam-emitting end.
[0080] FIG. 5 illustrates an alternate embodiment of the deflector 42 , notably by solidly connecting it to the body 2 of the housing 1 of the apparatus. More particularly, the deflector 42 has the general shape of a tuning fork and comprises a back wall 44 penetrated by dispensing openings 12 and extending to form an elbow connecting it to a deflection wall 43 spaced apart from said back wall. The deflection wall 43 is disposed remotely from and parallel to the back wall 44 and ends in a tip that curves back towards the latter. Such a deflector allows a lock of hair to pass between its parallel walls while protecting the scalp, and at the same time ensures that the steam is directed to the lock via the deflection wall. Advantageously, such a deflector can be made of plastic. The apparatus of FIG. 5 can be used alone for hair treatments, as the hair shaping device 30 is detachable.
[0081] In operation, the hair shaping device 30 is turned on by pressing a control switch, and a light (not shown in the drawings) can indicate when the heating plates have reached the correct temperature. A lock of hair is then introduced between the arms 33 , 34 of the hair shaping device 30 applying a pressure force to the lock, then the control switch 7 is pressed, and the apparatus starts to generate steam instantaneously. The apparatus is then moved along the lock for administering a steam treatment, which is followed immediately by a straightening through contact with the treatment surfaces 31 , 32 of the hair shaping device.
[0082] Because the controls of the device are independent from those of the apparatus, the latter can also be used with the straightening plates at ambient temperature or very slightly heated. This makes it possible to clean the lock, simultaneously ridding it of impurities and moisturizing it.
[0083] In a variant that is not shown in the drawings, the steam dispensing openings are located above the hair shaping device, in order to start with a straightening prior to the steam treatment.
[0084] Obviously, the invention is in no way limited to the embodiment described and illustrated, which was presented solely by way of an example. Modifications are possible, notably in terms of the constitution of the various elements or by substituting equivalent techniques, without exceeding the scope of protection for the invention in any way. | A portable apparatus for the steam treatment of hair includes a liquid tank, and a device for supplying a steam generator with liquid having a vaporisation chamber in thermal contact with an electric heating member, the vaporisation chamber communicating with one or more openings for dispensing steam towards a lock of hair. The generator is supplied with liquid by an electric pump, and the flow rate of the steam thus generated is higher than 5 g/min, and preferably of between 10 g/min and 60 g/min. | 0 |
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates to a paper dispenser, and more particularly to a device that is capable of facilitating the dispensation of sheets.
[0003] 2. Description of the Prior Arts
[0004] Most of office people like putting some sheets or memos on the desk for purpose of writing some information down in case of a phone-call or the likes. However, due to there is certain adhesive force between the surfaces of sheets, in their hurry to take the sheets, the users find their difficulties in precisely taking one sheet away from the stacks which usually give rise to the scattered falls of the sheets.
[0005] The present invention has arisen to mitigate and/or obviate the afore-described disadvantages of the conventional paper dispenser.
SUMMARY OF THE INVENTION
[0006] In accordance with one aspect of the present invention, there is provided a paper dispenser which generally comprises a chassis, an actuating member, a driven member, a paper pusher, an elastic member and a cover as a whole mounted to a paper box. The above-mentioned parts are assembled together so as to provide an interactive effect by pushing actions.
[0007] The primary objective of the present invention is to provide a paper dispenser that enables the user to take out sheets easily and quickly.
[0008] The present invention will become more obvious from the following description when taken in connection with the accompanying drawings, which shows, for purpose of illustrations only, the preferred embodiment in accordance with the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] [0009]FIG. 1 is an exploded view of a paper dispenser in accordance with the present invention;
[0010] [0010]FIG. 2 is a perspective view of the paper dispenser in accordance with the present invention;
[0011] [0011]FIG. 3 is a cross sectional view of the paper dispenser in accordance with the present invention;
[0012] [0012]FIG. 4 is a cross sectional view of showing the paper dispenser of the present invention mounted on the paper box;
[0013] [0013]FIG. 5 is another cross sectional view of showing the paper dispenser of the present invention mounted on the paper box.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0014] Referring to FIGS. 1-3, wherein a paper dispenser in accordance with the present invention is shown and generally comprises a chassis 10 , an actuating member 20 , a driven member 30 , a paper pusher 40 , an elastic member 50 and a cover 60 .
[0015] The chassis 10 generally includes a pair of long sides 11 and a pair of short sides 12 defining a space 13 therein. Two holes 111 are defined at each of the long sides 11 with corresponding to each other. In vicinity to each hole 111 a slot 112 is defined with one corresponding to another, and alike, in vicinity to the each slot 112 a strip groove 113 is formed also with corresponding to each other. Moreover, a hook 121 is disposed at a short side 12 where close to the holes 111 .
[0016] The actuating member 20 has a first and second end 21 , 22 . At the second end 22 recesses 221 are defined while at the first end 21 protrusions 211 are formed and serve to be received in the corresponding holes 111 of the chassis 10 respectively such that the actuating member 20 is permitted to move within the space 13 of the chassis 10 .
[0017] The driven member 30 is provided with a first end 31 and a second end 32 . At the first end 31 lugs 311 are disposed and serve to be received in the recesses 221 of the actuating member 20 respectively. While the second end 32 is corresponding to the strip grooves 113 and allowed to horizontally move in the space 13 of the chassis 10 .
[0018] The paper pusher 40 includes a pushing portion 41 and at both sides of the pushing portion 41 an arm 42 symmetrically is formed respectively. At the top of the pushing portion 41 a damper 411 is disposed for pushing sheets, while the pair of arms 42 serve to be engaged with the strip grooves 113 by passing a rod 43 through the arms 42 , the strip grooves 113 and the second end 32 of the driven member 30 respectively. By such arrangements, the paper pusher 40 is engaged with the driven member 30 and moves along with the movement of the same.
[0019] The elastic member 50 , here takes spring as example, has a first end connected to the hook 121 of the chassis 10 and a second end connected to the rod 43 such that the driven member 30 can be recovered to the original position by virtue of the elastic member 50 .
[0020] The cover 60 has a chamber 61 and at the bottom of which a contacting piece 62 is disposed, while at the outer periphery of the cover 60 projections 63 are formed with corresponding to slots 112 of the chassis 10 respectively. The chamber 61 of the cover 60 serves to mount onto the actuating member 20 and the driven member 30 with the contacting piece 62 butting around the center of the actuating member 20 while the two projections 63 received in the slots 112 for purpose of preventing the disengagement of the cover 60 from the chassis 10 . By such arrangements, the cover 60 enables the actuating member 20 , the driven member 30 and the paper pusher 40 connected in an interactive manner.
[0021] Referring to FIGS. 4-5, in which, a chassis 10 of the present invention is mounted to the paper box 70 and the paper box 70 interiorly formed with a space 71 and a stack of paper 80 is stocked therein. Moreover, the space 71 is provided with a guiding incline 72 , and at the top of the space 71 where corresponding to the guiding incline 72 an exit 73 is formed.
[0022] After the paper box 70 is mounted thereon, the paper pusher 40 possesses a suitable weight, and the damper 411 contacts with the first sheet 81 of the stack 80 . To take out the paper, what the user needs to do is only to push the cover 60 and the same is confined by the slots 112 only longitudinally movable due to the projections 63 of the same are movably received in the longitudinal slots 112 of the chassis 10 . And then the cover 60 moves downward with the contacting piece 62 butting the actuating member 20 so as to move the same, which further effects an movement of the driven member 30 since which is connected with the actuating member 20 and the horizontal movement of the second end 32 of the driven member 30 along the strip grooves 113 (namely move towards the exit 73 of the paper box 70 ). Such that the paper pusher 40 connected to the driven member 30 is driven to move with the damper 411 of the pushing portion 41 pushing the first sheet 81 of the stack 80 , thereby the user can take the first sheet 81 that moves out of the exit 73 along the guiding incline 72 .
[0023] On the other hand, the actuating member 20 moves with relative to the driven member 30 in case that the cover 60 is pushed, which effects a longitudinal expansion movement of the elastic member 50 and a restoring force of the same simultaneously. Such that, in case that the cover 60 is not pressed, the same and the actuating member 20 , the driven member 30 and together with the paper pusher 40 are driven back to the original position by the restoring force of the elastic member 50 , and wait for the next cycle of movement. By such a manner, the sheets may be taken out easily and quickly.
[0024] While we have shown and described various embodiments in accordance with the present invention, it should be clear to those skilled in the art that further embodiments may be made without departing from the scope of the present invention. | A paper dispenser generally comprises a chassis, an actuating member, a driven member, a paper pusher, an elastic member and a cover as a whole mounted to a paper box. The above-mentioned parts are assembled together so as to provide an interactive effect by pushing actions and paper pusher may push sheets smoothly, such that the user may take out the sheets easily and quickly. | 1 |
BACKGROUND OF THE INVENTION
The present invention relates to the packaging field, and more particularly to a laminated thermoplastic film which can be used to produce a heat-sealable, heat-shrinkable bag having a polyester external surface.
The use of heat-shrinkable thermoplastic films is well known to the packaging industry. For example, poultry products are typically sealed within bags made from such films and heated, thus shrinking the bag until it fits tightly about the product.
One type of thermoplastic material currently used to form such bags is monolayer polyester film. Polyester bags have many advantages. For instance, they provide strength and protection through tight adhesion to the product. Also, printing onto treated polyester tends to be somewhat more stable than onto other thermoplastic materials. However, a problem exists in that polyester is not heat-sealable except at exceptionally high temperatures, and as a result such bags must be sealed with adhesive. Bags sealed with adhesive are not as strong in the seal area as than heat sealed bags, cannot be closed on the open end by existing heat seal equipment and cannot be printed so as to lock or protect the printing.
A second type of heat-shrinkable bag currently in use is made of co-extruded, heat-shrinkable, thermoplastic films, such as polyolefin. For example, U.S. Pat. No. 3,299,194 to Golike and U.S. Pat. No. 3,663,662 to Golike et al. disclose shrink films of oriented polyethylene and various copolymers of ethylene. U.S. Pat. No. 4,597,920 to Golike teaches a shrink films which is a copolymer of ethylene with at least one C 8 -C 18 α-olefin. Methods for producing multi-layer thermoplastic film are provided in U.S. Pat. No. 2,855,517 to Rainer et al., U.S. Pat. No. 3,022,543 to Baird, U.S. Pat. No. 3,754,063 to Schirmer, and U.S. Pat. No. 3,981,008 to D'Entremont.
Coextruded films, such as polyolefins, are useful in producing heat-shrinkable bags because they are heat-sealable and therefore can be produced on existing heat seal equipment economically. They maintain good physical contact with a packaged product after heat shrinking, and thereby retain juices within packaged meats, but not as well as the laminated shrink bags. However, coextruded films have different mechanical properties, such as tensile strength and modulus, and therefore bags made from these films are more apt to tear or otherwise become physically damaged during handling than a multilayer lamination. Another important disadvantage is that you cannot reverse print or lock the print between the film layers, whether by surface or reverse print, with coextruded films, making them exposed to abuse, abrasion, and removal of the print by physical or chemical action.
Therefore, there exists a need for a thermoplastic film which combines the advantages and eliminates the disadvantages associated with monolayer polyester and coextruded films.
More particularly, there exists a need for a film which is strong, which is heat-sealable, and which eliminates the problem associated with surface printing.
SUMMARY OF THE INVENTION
The present invention relates to a heat-sealable, heat-shrinkable laminate film, as well as a bag or other packaging produced from the film.
The film is comprised of first layer of heat-shrinkable thermoplastic material laminated to a second layer of heat-sealable, heat-shrinkable thermoplastic material which has similar shrink characteristics to the first layer and an adhesive which adheres the two layers together. In this way, the first and second layers will shrink at approximately equal rates, thereby providing a uniform appearance and structural stability both during the lamination process and in a package produced with the film.
In one embodiment, the first layer may be a polyester, such as polyethylene terephthalate, and the second layer may be a polyolefin, such as polypropylene or polyethylene. The two layers may be adhered together on a standard laminating machine using processes that allows the lamination to occur without undue shrinking.
The film may be used to produce a heat-shrinkable package, such as a bag. For example, a length of the film may be folded to form two sections so that the second layers of each section contact one another to form the inner surface of the bag and the first layers form the outer surface of the bag. The edges of the sections may be heat-sealed to adhere the second layers together and produce the final bag structure.
Therefore, it should be clear that the present invention provides a thermoplastic film which combines the advantages and eliminates the disadvantages associated with monolayer polyester and co-extruded films. For instance, the film of the present invention may be used to produce a bag having a strong, printable polyester outer surface and a clean, heat sealable inner surface. Furthermore, indicia may be reverse printed on the inner surface of the first layer, or, the surface of the second layer, and thereby protected in the final product.
These and other advantages are explained in more detail in the following detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic diagram representing a cross-sectional view of the film of the present invention;
FIG. 2 is a perspective view of a heat-shrinkable bag made in accordance with the present invention; and
FIG. 3 is a cross-sectional view of a side of a bag made in accordance with the present invention.
DETAILED DESCRIPTION OF THE INVENTION
The heat-sealable, heat-shrinkable thermoplastic laminate film of the present invention has the cross-sectional appearance shown in FIG. 1. The film 10 comprises a substrate 12, or first layer, adhered to a second layer 14, by means of a layer of adhesive 16.
The substrate 12 is comprised of a sheet of polyester, such as HS heat-shrinkable polyethylene terephthalate (see, R. W. Moncrieff, Man-Made Fibres, John Wiley and Sons, New York, 4th ed., 1963). Polyethylene terephthalate typically has gauges from 50 to 150 and is designed to shrink approximately 50% at a temperature of 100° C. The specific type of polyethylene terephthalate employed depends upon the specific end use of the film 10. For example, if the end use is one that does not require a high barrier against moisture transmissions or oxygen permeability, the substrate 12 may be polyethylene terephthalate types HSV-65 or HSV-150, available from E. I. Du Pont de Nemours Company, Wilmington, Del. If an extremely high barrier against moisture vapor transmission, as well as against oxygen permeability, is desired, types XM-927-65 or XM 927-150, available from E. I. Du Pont de Nemours Company, Wilmington, Del., may be employed. These "XM" types are polyethylene terephthalate film coated with a polyvinyldine chloride coating, and are particularly useful for extending the shelf lives of meat or poultry products. A third type of film, such as HS-65 and HS-150, available from E. I. Du Pont de Nemours Company, Wilmington, Del., has a relatively high melting point and therefore is desirable for use in high temperature applications such as cooking meat products.
The second layer 14 may be of any thermoplastic material which is heat-sealable and which has approximately the same shrinking characteristics, attained by a blow-up ratio or orientation, as the substrate 12. For example, the second layer 14 may be comprised of a polyolefin, such as polypropylene or polyethylene. Also, a 1.00 mil to 3.00 mil ionomer extrusion produced by Tara Plastics of College Park, Georgia from one of #1601, #1650 and #1652 Surlyn® resin (ethylene-methacrylic acid di-and ter-polymers) supplied by E. I. DuPont de Nemours and Company may be used. The ionomer is particularly useful in that it has been found to adhere to packaged meat during cooking and prevent loss of juices therefrom during this process. The second layer 14 may be produced by standard extruding to a blow-ratio or orientation conducive to shrink, and should achieve an approximately 50% shrink at 100° C.
The term "shrink characteristics" means the ability of film to be oriented in such a way as to cause it to shrink in size, both longitudinally and latitudinally when subjected to certain temperature levels. This orientation causes a change in the molecular structure of the film, that when subjected to the higher temperature causes this molecule configuration to attempt to return to its original structure. This can be done in a number of ways, but all include the changing of time, temperature and pressure on the film.
The adhesive layer 16 may be comprised of any type of adhesive which will effectively secure the substrate 12 to the second layer 14 for the intended purposes of the film 10. For example, the adhesive must maintain the attachment at high temperatures so that the film 10 can survive heat shrinking, as well as cooking if so desired, without damage. One adhesive which may be used is a polyurethane type lamal HSA adhesive and a CR180 catalyst, available from Morton Thiokol Inc., Morton Chemical Division, Chicago, Ill. Another type of adhesive may be a water based adhesive, such as Morton #2018.
Printed matter 18 may be placed onto the substrate 12 in any known manner. The printing may be provided on the outer surface 20 of the substrate 12, in which case the printing process may be performed either before or after the adhering of the substrate 12 and second layer 14. It is also possible to provide the printed matter 18 on the inner surface 22 of the substrate 12 so that the printing becomes protected between the substrate 12 and second layer 14 in the film 10. Printed matter 18 may also be placed on the inside surface of sealing layer 16 in which case the printed matter would also become protected between the substrate 12 and the second layer 14 in the film 10.
The film 10 may be produced on a standard laminating machine, such as available from Dri Tech, New Berlin, Wis. The similarity in shrink characteristics of the substrate 12 and second layer 14 eliminates problems caused by the heat shrink associated with production. A roll of substrate 12 and a roll of the second layer 14 are held separately on the laminating machine. The rolls are unwound into the lamination process while the machine speed is set at approximately 300 to 400 feet per minute, the oven temperature at approximately 22° C.-82° C. (72° F.-180° F.), the web temperature at the same temperature as the oven, and the adhesive applied at a weight of 1.25±0.25 lbs. per ream. The laminator nip temperature should be approximately 65° C. (150° F.) and the nip pressure should be approximately 30-50 P.S.I. using a first treater set at 20 to 40% and a second treater set at 50 to 90%. The chill rolls should set the film 10 running at 15° to 27° C. (60° F.-80° F.).
The film 10 may be made into shrinkable bags 24, such as shown in FIG. 2. The bag 24 may be produced by folding a sheet of film 10 into two equal length sections 26,28 so that the substrate 12 comprises the outside portion 30 of the bag 24 and the second layer 14 comprises the inside portion 32. To complete the bag 24, the side edges 34 of the film 10 are heat sealed together, preferably at a low temperature, such as by impulse sealing. As shown in cross-sectional view in FIG. 3, upon application of heat, the second layer 14 of the first section will seal to the second layer 14 of the second section. | A heat-sealable, heat-shrinkable laminate film having a first layer of heat-shrinkable thermoplastic material and a second layer of heat-sealable, heat-shrinkable thermoplastic material adhered to the first layer, the materials of the first and second layers having similar shrink characteristics. | 1 |
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims priority to and the benefit of Korean Patent Application No. 10-2010-0123450 filed in the Korean Intellectual Property Office on Dec. 6, 2010, the entire contents of which are incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] (a) Field of the Invention
[0003] The present invention relates to a method and a system for controlling torque of a hybrid vehicle. More particularly, the present invention relates to a method and a system for controlling torque of a hybrid vehicle that calculates power and torque of each motor when the hybrid vehicle provided with two motors operates at a transient state.
[0004] (b) Description of the Related Art
[0005] Generally, a hybrid vehicle is a vehicle which uses an engine and a motor as power source. The hybrid vehicle may be provided with one motor and one engine, but the hybrid vehicle provided with two motors and one engine is increasingly more popular in today's market. In this case, a first motor is used for controlling engine speed and a second motor is used for compensating engine torque according to the engine speed controlled by the first motor and generating demand torque.
[0006] A control portion of the hybrid vehicle determines target driving points of the engine and the first and second motors by using vehicle's speed, the demand torque, and the state of charge (SOC). However, such target driving points of the engine and each motor are determined under the assumption that the hybrid vehicle operates at a steady state. Therefore, when a hybrid vehicle operates at a transient state, actual driving points of the engine and each motor differs from the target driving points and logic for determining driving points of the engine and each motor at the transient state may be necessary.
[0007] In order to determine the driving points of each motor at the transient state, a priority order is necessary. That is, if the driving points of two motors at the transient state are simultaneously determined, a large error may occur. Therefore, after the driving point of one motor is determined, the driving point of the other motor is determined by using the driving point of just the one motor.
[0008] The above information disclosed in this Background section is only for enhancement of understanding of the background of the invention and therefore it may contain information that does not form the prior art that is already known in this country to a person of ordinary skill in the art.
SUMMARY OF THE INVENTION
[0009] The present invention has been made in an effort to provide a method and a system for controlling torque of a hybrid vehicle having advantages of determining power and torque of each motor at a transient state.
[0010] Particularly, a method and a system for controlling torque of a hybrid vehicle in which power and torque of a first motor for controlling engine speed is determined, and power and torque of a second motor for compensating engine torque and generating demand torque is determined by using the power and the torque of the first motor.
[0011] A method for controlling torque of a hybrid vehicle according to an exemplary embodiment of the present invention may determine torque and power of each motor in the hybrid vehicle provided by a first motor controlling engine speed and a second motor for compensating engine torque and generating demand torque. The method may include: determining target power of a battery based on vehicle speed, the demand torque, and SOC; calculating target torque of the first motor, target torque of the second motor, target torque of an engine, and target speed of the engine at a steady state based on the vehicle speed, the demand torque, and the target power of the battery; calculating torque of the first motor at a transient state from the target torque of the second motor at to the steady state and speeds of the first and second motors; and calculating torque of the second motor at the transient state from the torque of the first motor at the transient state and the speeds of the first and second motors.
[0012] Calculation of the torque of the first motor at the transient state may include: calculating the target power of the second motor at the steady state from the target torque of the second motor at the steady state and the speed of the second motor; calculating maximum power of the first motor at the transient state from the target power of the second motor at the steady state and power limit of a power source; and calculating maximum torque of the first motor at the transient state from the maximum power of the first motor at the transient state and the speed of the first motor.
[0013] The calculation of the torque of the first motor at the transient state may further include: calculating the target torque of the first motor at the transient state based on the target speed of the engine at the steady state and the speeds of the first and second motors; and determining the torque of the first motor at the transient state by comparing the maximum torque of the first motor and the target torque of the first motor at the transient state.
[0014] Calculation of the torque of the second motor at the transient state may include: calculating power of the first motor at the transient state from the torque of the first motor at the transient state and the speed of the first motor; calculating maximum power of the second motor at the transient state from the power of the first motor at the transient state and the power limit of the power source; and calculating maximum torque of the second motor at the transient state from the maximum power of the second motor at the transient state and the speed of the second motor.
[0015] The calculation of the torque of the second motor at the transient state may further include: calculating target torque of the second motor at the transient state based on the demand torque and the torque of the first motor at the transient state; and determining the torque of the second motor at the transient state by comparing the maximum torque of the second motor and the target torque of the second motor at the transient state. The power of the first motor at the transient state may be filtered so as to calculate the maximum power of the second motor at the transient state.
[0016] A system for controlling torque of a hybrid vehicle according to the exemplary embodiment of the present invention may include: an engine; a first motor for controlling engine speed; a second motor compensating engine torque and generating demand torque; and a control portion controlling the engine, the first motor, and the second motor. In particular, the control portion calculates torque of the first motor at a transient state by using target torque of the second motor at a steady state, and calculates torque of the second motor at the transient state by using the torque of the first motor at the transient state.
[0017] The control portion may calculate target power of the second motor at the steady state by using the target torque of the second motor at the steady state and speed of the second motor. The maximum power of the first motor is then calculated at the transient state by using the target power of the second motor at the steady state and power limit of a power source. Further, the maximum torque of the first motor is calculated at the transient state by using the maximum power of the first motor at the transient state and speed of the first motor.
[0018] The control portion may calculate target torque of the first motor at the transient state based on target speed of the engine at the steady state and the speeds of the first and second motors, and may determine the torque of the first motor at the transient state to by comparing the maximum torque of the first motor at the transient state with the target torque of the first motor.
[0019] The control portion may also calculate power of the first motor at the transient state by using the torque of the first motor at the transient state and the speed of the first motor. Then the maximum power of the second motor is calculated at the transient state by using the power of the first motor at the transient state and the power limit of the power source. The maximum torque of the second motor is calculated at the transient state by using the maximum power of the second motor at the transient state and the speed of the second motor.
[0020] The control portion may calculate target torque of the second motor at the transient state based on the demand torque and the torque of the first motor at the transient state. Then the control portion may determine the torque of the second motor at the transient state by comparing the maximum torque of the second motor at the transient state and the target torque of the second motor.
BRIEF DESCRIPTION OF THE DRAWINGS
[0021] The above and other features of the present invention will now be described in detail with reference to certain exemplary embodiments thereof illustrated the accompanying drawings which are given hereinbelow by way of illustration only, and thus are not limitative of the present invention, and wherein:
[0022] FIG. 1 is a schematic diagram illustrating a transmission of a hybrid vehicle to which a method for controlling torque according to an exemplary embodiment of the present invention can be applied.
[0023] FIG. 2 is a block diagram of a system for controlling torque of a hybrid vehicle to according to an exemplary embodiment of the present invention.
[0024] FIG. 3 is a flowchart of a method for controlling torque of a hybrid vehicle according to an exemplary embodiment of the present invention.
[0025] FIG. 4 is a flowchart illustrating calculation of power and torque of the first motor according to an exemplary embodiment of the present invention.
[0026] FIG. 5 is a flowchart illustrating calculation of power and torque of the second motor according to an exemplary embodiment of the present invention.
[0027] It should be understood that the appended drawings are not necessarily to scale, presenting a somewhat simplified representation of various preferred features illustrative of the basic principles of the invention. The specific design features of the present invention as disclosed herein, including, for example, specific dimensions, orientations, locations, and shapes will be determined in part by the particular intended application and use environment.
[0028] In the figures, reference numbers refer to the same or equivalent parts of the present invention throughout the several figures of the drawing.
DETAILED DESCRIPTION OF THE EMBODIMENTS
[0029] An exemplary embodiment of the present invention will hereinafter be described in detail with reference to the accompanying drawings.
[0030] FIG. 1 is a schematic diagram illustrating a transmission of a hybrid vehicle to which a method for controlling torque according to an exemplary embodiment of the present invention can be applied. As shown in FIG. 1 , a transmission of a hybrid vehicle to which a method for controlling torque according to an exemplary embodiment of the present invention can be applied uses an engine 10 and first and second motors 30 and 40 as power sources. The engine 10 generates power by burning e.g., fuel. Various types of engines such as a gasoline engine, a diesel engine, an LPI engine may be used as the engine 10 .
[0031] Power of the engine 10 is input to first and second planetary gear sets PG 1 and PG 2 through an input shaft 12 . The first planetary gear set PG 1 includes a first sun gear S 1 , a first planet carrier C 1 , and a first ring gear R 1 as rotation elements thereof. The first sun gear S 1 is may be always connected to the first motor 30 , and the first planet carrier C 1 may be always connected to the engine 10 . In addition, a first brake BK 1 is interposedly connected between the first sun gear S 1 and the first motor 30 so as to selectively stop the first motor 30 upon demand.
[0032] The second planetary gear set PG 2 includes a second sun gear S 1 , a second planet carrier C 2 , and a second ring gear R 2 as rotation elements thereof. The first planet carrier C 1 is selectively connected to the second ring gear R 2 through a first clutch CL 1 , and the first ring gear R 1 is directly connected to the second planet carrier C 2 . In addition, the second sun gear S 2 is selectively connected to the engine 10 through a second clutch CL 2 while at the same time being continuously connected to the second motor 40 . The second ring gear R 2 may be selectively stopped by a second brake BK 2 , and the second planet carrier C 2 may be continuously connected to an output gear 20 .
[0033] Operationally, the first motor 30 controls engine speed input to the first planet carrier C 1 through the first sun gear S 1 . The first planet carrier C 1 delivers the engine speed to the output gear 20 through the first ring gear R 1 and the second planet carrier C 2 . [The speed of the first motor is combined with the speed of the engine, and the target speed (i.e., controlled by the speed of the first motor and the speed of the engine) to that is output to the output gear. Thus, if the speed of the first motor is determined, the engine speed is controlled according to the speed of the first motor and the target speed.
[0034] The second motor 40 compensates engine torque input through the first planet carrier C 1 and engine torque selectively input through the second sun gear S 2 so that demand torque is output through the output gear 20 . That is, the second motor 40 compensates the engine torque so as to generate the demand torque accordingly.
[0035] A battery 50 supplies electricity/power to the first and second motors 30 and 40 while operating in a first mode and is charged by electricity generated at the first and second motors 30 and 40 under a predetermined driving condition in a second mode to thereby keep the battery charge above a certain level.
[0036] FIG. 2 is a block diagram of a system for controlling torque of a hybrid vehicle according to an exemplary embodiment of the present invention. As shown in FIG. 2 , a system for controlling torque of a hybrid vehicle according to an exemplary embodiment of the present invention includes a vehicle speed detector 62 , a first motor speed detector 64 , a second motor speed detector 66 , an SOC detector 68 , a control portion 60 , and the first and second motors 30 and 40 . In addition, a plurality of sensors for detecting operations of the engine 10 , the transmission, the first and second motors 30 and 40 , and the battery 50 may be further included.
[0037] In this embodiment, the vehicle speed detector 62 detects the current vehicle speed and delivers a signal corresponding thereto to the control portion 60 . The first motor speed detector 64 detects the current speed of the first motor 30 and delivers a signal corresponding thereto to the control portion 60 . The second motor speed detector 66 detects the current speed of the second motor 40 and delivers a signal corresponding thereto to the control portion 60 . The SOC detector 68 detects SOC of the battery 50 and delivers a signal corresponding thereto to the control portion 60 .
[0038] The control portion 60 determines driving points of the engine and each motor at a steady state based on the vehicle speed, the speeds of the first and second motors 30 and 40 , and the SOC of the battery 50 , and determines driving points of each motor at a transient state. The control portion 60 controls operations of the engine 10 , the first motor 30 , and the second motor 40 according to the determined driving points.
[0039] Hereinafter, a method for controlling torque of a hybrid vehicle according to an exemplary embodiment of the present invention will be described in detail with reference to FIG. 3 to FIG. 5 .
[0040] FIG. 3 is a flowchart of a method for controlling torque of a hybrid vehicle according to an exemplary embodiment of the present invention, FIG. 4 is a flowchart illustrating calculation of power and torque of the first motor according to an exemplary embodiment of the present invention, and FIG. 5 is a flowchart illustrating calculation of power and torque of the second motor according to an exemplary embodiment of the present invention.
[0041] As shown in FIG. 3 , a method for controlling torque of a hybrid vehicle according to an exemplary embodiment of the present invention includes determining target power of the battery at a step S 100 , calculating driving points of the engine 10 and each motor 30 and 40 at the steady state at a step S 200 , and calculating driving points of each motor 30 and 40 at the transient state at a step S 300 .
[0042] The control portion 60 calculates demand torque based on the current vehicle speed, a position of an accelerator pedal, and engine speed at a step S 112 , receives the current vehicle speed from the vehicle speed detector 62 at a step S 114 , and receives the SOC of the battery 50 from the SOC detector 68 at a step S 116 . In addition, the control portion 60 receives a charge/discharge limit at a step S 118 , and receives constraint conditions of the engine 10 and each motor 30 and 40 at step S 120 . The charge/discharge limit and the constraint conditions of the engine 10 and each motor 30 and 40 may be stored in the control portion 60 for later use in for example RAM memory.
[0043] The control portion 60 then determines power of the battery 50 from the vehicle speed, the demand torque, and the charge/discharge limit at a step S 121 , and determines target power of the battery 50 by comparing the power of the battery 50 with the charge/discharge limit at a step S 122 .
[0044] After that, the control portion 60 determines the target driving point at the steady state by using the demand torque, the vehicle speed, the target power of the battery 50 , and the constraint conditions of the engine 10 and each motor 30 and 40 at a step S 202 . That is, target torque of the first motor 30 at the steady state is calculated at a step S 204 , the target torque of the second motor 40 at the steady state is calculated at a step S 206 , the target torque of the engine 10 at the steady state is calculated at a step S 208 , and target speed of the engine 10 at the steady state is calculated at a step S 210 . In addition, the control portion 60 receives the speed of the second motor 40 from the second motor speed detector 66 at a step S 212 , and receives the speed of the first motor 30 from the first motor speed detector 64 at a step S 214 .
[0045] Next, the control portion 60 calculates target speed of the first motor 30 from the target speed of the engine 10 at the steady state and the speed of the second motor 40 at a step S 216 , and subtracts the speed of the first motor 30 from the target speed of the first motor 30 at a step S 302 .
[0046] The control portion 60 calculates the target torque of the first motor 30 at the transient state by using the difference between the target speed of the first motor 30 and the speed of the first motor 30 at a step S 304 , and limits torque of the first motor 30 by using the target torque of the first motor 30 , the charge/discharge limit of the first motor 30 (determined from the charge/discharge limit of a power source (the battery 50 )), the target power of the second motor 40 at the steady state, and the speed of the first motor 30 at a step S 310 . Accordingly, torque of the first motor 30 at the transient state is calculated at a step S 312 .
[0047] In addition, the control portion 60 calculates target torque of the second motor 40 at the transient state by subtracting the torque of the first motor 30 at the transient state from the demand torque at a step S 316 . In addition, the control portion 60 limits torque of the second motor 40 by using the target torque of the second motor 40 at the transient state, the charge/discharge limit of the second motor 40 , the power of the first motor at the transient state, and the speed of the second motor 40 at a step S 320 . Accordingly, the torque of the second motor 40 at the transient state is calculated at a step S 322 .
[0048] Referring to FIG. 4 , processes for calculating the torque of the first motor 30 at the transient state will be described in detail.
[0049] The control portion 60 calculates target power of the second motor 40 at the steady state by multiplying the target torque of the second motor 40 at the steady state and the speed of the second motor 40 at a step S 330 , and multiplies a first gain to the target power of the second motor 40 at the steady state at a step S 332 .
[0050] The control portion 60 calculates maximum discharge power of the first motor 30 at the transient state from discharge power limit of the first motor 30 , the target power of the second motor 40 at the steady state, and the first gain at a step S 334 . In addition, the control portion 60 calculates maximum discharge torque of the first motor 30 at the transient state by using the maximum discharge power of the first motor 30 at the transient state and the speed of the first motor 30 at a step S 336 . The maximum discharge torque in this case may be calculated from a predetermined discharge efficiency map.
[0051] Similar to the calculation of the maximum discharge torque, the control portion 60 calculates maximum charge torque of the first motor 30 at the transient state at a step S 344 . That is, the control portion 60 calculates the maximum charge power of the first motor 30 at a transient state from the charge power limit of the first motor 30 , the target power of the second motor 40 at the steady state, and the first gain at a step S 342 , and calculates the maximum charge torque of the first motor 30 at the transient state by using the maximum charge power of the first motor 30 at the transient state and the speed of the first motor 30 at a step S 344 .
[0052] The control portion 60 determines whether charge or discharge occurs by multiplying the target torque of the first motor 30 at the transient state and the speed of the first motor 30 at a step S 338 , and determines whether the maximum charge torque or the maximum discharge torque of the first motor 30 at the transient state is used at a step S 340 based on whether the sign is positive (+) or negative (−), respectively.
[0053] The control portion 60 calculates absolute value of the target torque of the first motor 30 at the transient state at a step S 346 , and compares the maximum charge torque or the maximum discharge torque determined at the step S 340 with the absolute value of the target torque at a step S 348 . After that, the control portion 60 calculates the torque of the first motor 30 at the transient state at the step S 312 . At S 348 , a minimum value is chosen. Since the step S 348 is performed without sign, the sign is added at the step S 312 as shown in FIG. 4 .
[0054] Referring to FIG. 5 , processes for calculating the torque of the second motor 40 at the transient state will be described in detail.
[0055] The control portion 60 calculates power of the first motor 30 at the transient state from the torque of the first motor 30 at the transient state and the speed of the first motor 30 at a step S 350 , and filters the power of the first motor 30 at the transient state at a step S 352 such that the torque of the second motor 40 at the transient state is not affected by fluctuation of the power of the first motor 30 at the transient state.
[0056] The control portion 60 subtracts the filtered power of the first motor 30 at the transient state from discharge power limit of the second motor 40 at a step S 354 , and calculates maximum discharge power of the second motor 40 at the transient state from the discharge power limit of the second motor 40 (calculated from the charge/discharge limit of the power source (the battery 50 )), the filtered power of the first motor 20 at the transient state, and a second gain at a step S 356 . In addition, the control portion 60 calculates maximum discharge torque of the second motor 40 at the transient state by using the maximum discharge power of the second motor 40 at the transient state and the speed of the second motor 40 at a step S 358 . The maximum discharge torque is calculated from the predetermined discharge efficiency map.
[0057] Similar to calculation of the maximum discharge torque, the control portion 60 calculates maximum charge torque of the second motor 40 at the transient state at a step S 366 . That is, the control portion 60 calculates maximum charge power of the second motor 40 at the transient state from charge power limit of the second motor 40 , the filtered power of the first motor 30 at the transient state, and the second gain at a step S 364 , and calculates the maximum charge torque of the second motor 40 at the transient state by using the maximum charge power of the second motor 40 at the transient state and the speed of the second motor 40 at the step S 366 .
[0058] After that, the control portion 60 determines whether charge or discharge occurs by multiplying the target torque of the second motor 40 at the transient state and the speed of the second motor 40 at a step S 360 , and determines whether the maximum charge torque or the maximum discharge torque of the second motor 40 at the transient state is used at a step S 362 based on whether the sign is positive (+) or negative (−), respectively.
[0059] The control portion 60 calculates absolute value of the target torque of the second motor 40 at the transient state at a step S 368 , and compares the maximum charge torque or the maximum discharge torque determined at the step S 362 with the absolute value of the target torque at a step S 370 based on whether the sign is positive (+) or negative (−), respectively. After that, the control portion 60 calculates the torque of the second motor 40 at the transient state at a step S 322 .
[0060] Furthermore, the control mechanisms/portions of the present invention may be embodied as computer readable media on a computer readable medium containing executable program instructions executed by a processor. Examples of the computer readable mediums include, but are not limited to, ROM, RAM, compact disc (CD)-ROMs, magnetic tapes, floppy disks, and optical data storage devices. The computer readable recording medium can also be distributed in network coupled computer systems so that the computer readable media is stored and executed in a distributed fashion, e.g., wirelessly to a remote server.
[0061] As described above, since power and torque of a second motor generating final demand torque is determined after power and torque of a first motor controlling engine to speed is determined, optimal torque of each motor at a transient state may be calculated according to an exemplary embodiment of the present invention.
[0062] In addition, since each motor and an engine are controlled by using optimal torque of each motor, fuel economy may be improved and an SOC may be managed stably.
[0063] While this invention has been described in connection with what is presently considered to be practical exemplary embodiments, it is to be understood that the invention is not limited to the disclosed embodiments, but, on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims. | The present invention controls torque of a hybrid vehicle that calculates power and torque of each motor when the hybrid vehicle provided with two motors operates at a transient state are used. More specifically, target power of a battery is determined. Then calculations are performed to determine target torque of the first motor, target torque of the second motor, target torque of an engine, and target speed of the engine at a steady state. The torque of the first motor at a transient state is calculated from the target torque of the second motor at the steady state and speeds of the first and second motors. Finally, torque of the second motor at the transient state is calculated from the torque of the first motor at the transient state and the speeds of the first and second motors. | 1 |
This application is a continuation-in-part application of U.S. patent application Ser. No. 09/327,240, filed Jun. 7, 1999, hereby incorporated herein in its entirety.
FIELD OF THE INVENTION
The invention is directed toward methodologies and apparatus for use in the preparation of acellular, i.e. essentially lacking in living cells and/or non-living cells, soft-tissue implants, in small quantities and commercializable quantities. Such soft-tissue implants include vascular graft substitutes. These implants can be derived from tissue engineered soft tissue devices, tissue products derived from animal or human donors that contain or are devoid of cells, and that contain or are devoid of valve structures useful in directing the flow of fluids through tubular vascular devices, and/or combinations of natural tissue products and tissue engineered soft-tissue products. The invention includes methodologies and apparatus for producing uniform, gently processed, decellularized multiple soft tissue implants, where processing time is significantly reduced and the number of implants produced per day is increased. The decellularized grafts produced are significantly improved in long-term durability and function when used in clinical applications.
BACKGROUND OF THE INVENTION
Numerous types of vascular graft substitutes have been produced in the last four decades. These vascular graft substitutes have included large and small diameter vascular, blood carrying tubular structures, grafts containing valvular structures (vein substitutes, and heart valve substitutes) and lacking valvular structures (artery substitutes). The materials out of which these vascular grafts have been constructed have included man-made polymers, notably Dacron and Teflon in both knitted and woven configurations, and non-man-made polymers, notably tissue engineered blood vessels such as described in U.S. Pat. Nos. 4,539,716; 4,546,500; 4,835,102; and blood vessels derived from animal or human donors such as described in U.S. Pat. Nos. 4,776,853; 5,558,875; 5,855,617; 5,843,181; and 5,843,180.
The prior art processing methods are prohibitively time consuming, easily requiring numerous days, for example anywhere from eight to twenty-one days total processing time. Such long processing times result in proteolytic degradation of the matrix structures of the processed tissues. Over the past few decades numerous efforts have been made to manage the large surgical use of vascular prostheses in the treatment of vascular dysfunctions/pathologies. While vascular prostheses are available for clinical use, they have met with limited success due to cellular and immunological complications, and the inability to remain patent and function. These problems are especially pronounced for small diameter prostheses, i.e. less than about 6 mm. Efforts have been directed at removing those aspects of allograft and xenograft vascular prostheses that contribute to immunological “rejection” and these efforts have focused primarily on development of various “decellularization” processes, which processes require unduly burdensome incubation times. In addition the prior art methods involve using volumes of processing solutions which do not lend themselves to the production of large numbers of vascular grafts, which ability to “scale-up” is necessary for economic clinical use.
The inventive process produces acellular grafts including but not limited to ligaments, tendons, menisci, cartilage, skin, pericardium, dura mater, fascia, small and large intestine, placenta, veins, arteries, and heart valves. The process is advantageous over prior art processes in that processing times and conditions have been optimized and reduced, and the economics of production have been dramatically improved, resulting in large numbers of uniform, non-immunogenic grafts being produced. The grafts produced are non-immunogenic, are substantially free from damage to the matrix, and are substantially free from contamination including for example free from infectious agents.
The invention involves the use of an anionic agent, for example sodium dodecylsulfate (SDS), for the treatment of tissues with the dual objective of decellularization and treatment of tissues to restrict recellularization. Further, the invention expands on the process of treating tissue(s) with SDS, describing how the amount(s) of SDS deposited in the tissue(s) can be further enhanced/reduced to either further inhibit recellularization of the tissue OR enhance recellularization of the tissue. Treatment of tissues with salt solutions prior to treatment with SDS results in different patterns of SDS deposition/precipitation in the tissues than treatment of tissues with SDS followed by treatment of tissues with salt solutions. Treatment of tissues with SDS prior to salt treatment can be expected to result in significant binding of SDS, primarily via hydrophobic interactions, to matrix “proteins” with further deposition of SDS in the tissues as salt precipitated materials by salt precipitation post SDS treatment. Treatment of tissues with salt solutions prior to treatment with SDS solutions can be expected to result in significant precipitation of SDS as a salt precipitated form and less SDS being bound to tissue matrix structure(s) via hydrophobic interactions. It is further understood that the particular salt solution used, either prior to or following SDS treatment, can significantly alter the subsequent solubility of the salt precipitated SDS and thus long-term retention of SDS in the tissues post implantation. The observed salt effects on both precipitability of SDS and subsequent resolubilization of the salt precipitated form of SDS indicate an activity order of Ca>Mg>Mn>K>Na and calcium salts of dodecylsulfate (CaDS) are less soluble and thus more slowly released from treated tissues than, for example, sodium salts of dodecylsulfate (SDS). The invention is directed at a process for producing acellular soft-tissue implants including vascular grafts, veins, arteries, and heart valves, where processing times and conditions have been optimized to dramatically improve on the economics of production as well as to produce a graft with minimum damage to the matrix structure of the acellular graft. It is a further objective of the present invention to describe how to control the amount(s) of anionic detergents, for example sodium dodecylsulfate (SDS), deposited in the tissue(s) with the objective of enhancing or restricting subsequent recellularization.
SUMMARY OF THE INVENTION
The inventive process is a process for preparing biological material(s) for implantation into a mammalian cardiovascular system, musculoskeletal system, or soft tissue system. The process removes cellular membranes, nucleic acids, lipids, and cytoplasmic components and produces an implant having an extracellular matrix including as major components collagens, elastins, proteoglycans, and mucopolysaccharides.
The process provides for the production of commercializable quantities of acellular soft tissue grafts for implantation into mammalian systems by removing the cellular populations, cellular remnants, nucleic acids, and small molecular weight proteins, lipids, and polysaccharides forming an acellular nonsoluble matrix having as major components collagens, elastins, hyaluronins, and proteoglycans. The acellular tissue produced can be implanted into a mammalian system, or recellularized in vitro and subsequently implanted into a mammalian system.
An embodiment of the process includes the following steps:
isolating from a suitable donor a desired tissue sample of the biological material;
extracting the tissue with mildly alkaline hypotonic buffered solution of an endonuclease such as Benzonase® (a registered product of Merck KGaA, Darmstadt, Germany) and a nonionic detergent formulation such as Allowash Solution™ (a registered trademark product of LifeNet, Virginia Beach, Va.);
optionally treating the tissue with a hypertonic buffered salt solution;
extracting and treating the tissue with a mildly alkaline hypotonic buffered solution of sodium dodecylsulfate, optionally with 0.1 to 0.5 M sodium chloride rendering the solution hypertonic;
optionally treating the tissue with a hypertonic buffered salt solution;
washing the tissue with ultrapure water followed by a water solution of chlorine dioxide; and
storage in a sealed container in isotonic saline, chlorine dioxide or 70% isopropanol.
The invention provides a process for preparing an acellular soft tissue graft for implantation into a mammalian system, including extracting a soft tissue sample with an extracting solution including one or more nonionic detergents and one or more endonucleases, to produce extracted tissue; treating the extracted tissue with a treating solution including one or more anionic detergents, to produce a treated tissue; washing the treated tissue with a decontaminating solution including one or more decontaminating agents to produce the acellular soft tissue graft; and storing the acellular soft tissue graft in a storage solution comprising one or more decontaminating agents.
The invention further provides a process for preparing commercializable quantities of acellular soft tissue grafts for implantation into mammalian systems, including obtaining tissue samples from an acceptable donor; extracting the tissue samples with an extracting solution including one or more nonionic detergents and one or more endonucleases, to produce extracted tissue; treating the extracted tissue with a treating solution including one or more anionic detergents, to produce a treated tissue; washing the treated tissue with a decontaminating solution including one or more decontaminating agents to produce the acellular soft tissue graft; and storing the acellular soft tissue graft in a storage solution including one or more decontaminating agents.
The invention also provides a process for preparing an acellular soft tissue graft for implantation into a mammalian system, including inducing a pressure mediated flow of an extracting solution including one or more nonionic detergents and one or more endonucleases, through soft tissue, to produce extracted tissue; inducing a pressure mediated flow of a treating solution including one or more anionic detergents, through the extracted tissue, to produce a treated tissue; inducing a pressure mediated flow of a decontaminating solution including one or more decontaminating agents through the treated tissue, to produce the acellular soft tissue graft; and storing the acellular soft tissue graft in a storage solution including one or more decontaminating agents.
The invention provides a process where the extracting solution is recirculated through the soft tissue graft.
The invention further provides a process where the treating solution is recirculated through the soft tissue graft.
The invention also provides a process where the decontaminating solution is recirculated through the soft tissue graft.
The invention provides a process for producing an acellular tissue graft and includes the use of calcium salts which use results in the acellular tissue graft containing a significantly more insoluble form of salt precipitated anionic detergent, which results in retarded recellularization of the acellular tissue graft in vivo or in vitro.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 illustrates a view of one embodiment of the processing chamber showing flow mediated processing of long vein segments.
FIG. 2 illustrates a view of an embodiment of the processing chamber showing flow mediated processing of a heart valve.
FIG. 3 illustrates a view of an unprocessed human saphenous vein examined with Hemoxylin and Eosin staining, magnified 20 times.
FIG. 4 illustrates a view of an unprocessed human saphenous vein examined with Feulgen staining, magnified 20 times.
FIG. 5 illustrates a view of a decellularized human saphenous vein examined with Hemoxylin and Eosin staining, magnified 20 times.
FIG. 6 illustrates a view of a decellularized human saphenous vein examined with Feulgen staining, magnified 20 times.
FIG. 7 is a bar graph illustrating the percent reduction in nucleic acids extractable from human saphenous veins using the inventive process.
FIGS. 8A & 8B are graphs illustrating the binding of a nonionic detergent, tritiated Triton X-100, to human saphenous vein versus time of incubation.
FIGS. 9A & 9B are graphs illustrating the release of a nonionic detergent, tritiated Triton X-100, from human saphenous vein versus time of incubation.
FIGS. 10A & 10B are graphs illustrating the binding of an anionic detergent, tritiated sodium dodecylsulfate, to human saphenous vein versus time of incubation.
FIGS. 11A & 11B are graphs illustrating the release of an anionic detergent, tritiated sodium dodecylsulfate, from human saphenous vein versus time of incubation.
FIGS. 12A & 12B are graphs illustrating the toxicity of a nonionic detergent, Triton X-100, towards mammalian cells in in vitro culture, on days 1 and 7, respectively.
FIGS. 13A & 13B are graphs illustrating the toxicity of an anionic detergent, sodium dodecylsulfate, towards mammalian cells in in vitro culture, on days 1 and 7, respectively.
FIG. 14 is a graph illustrating the ability of detergents to disrupt and solubilize mammalian cells.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Definitions. The below definitions serve to provide a clear and consistent understanding of the specification and claims, including the scope to be given such terms.
Allowash™ Solution
By the term “Allowash™ solution” is intended those compositions disclosed in U.S. Pat. No. 5,556,379 incorporated herein by reference. Examples of suitable Allowash™ compositions include: A cleaning composition containing about 0.06 wt % polyoxyethylene-4-lauryl ether; about 0.02 wt % poly (ethylene glycol)-p-nonyl-phenyl-ether; about 0.02 wt % octylphenol-ethyleneoxide and endotoxin free deionized/distilled water.
Decontaminating Agent
By the term “decontaminating agent” is intended one or more agents which remove or inactivate/destroy any infectious material potentially present in a biological tissue sample, for example, such agents include but are not limited to one or more of the following: an antibacterial agent; an antiviral agent; an antimycotic agent; an alcohol for example, methyl, ethyl, propyl, isopropyl, butyl, and/or t-butyl; trisodium phosphate; a preservative such as chlorine dioxide, isopropanol, METHYLPARABIN® (Croda, Inc.), antimicrobials, antifungal agents, sodium hydroxide; hydrogen peroxide; a detergent, and ultrapure water, where the decontaminating agent or agents do not chemically alter the matrix components of the soft tissue grafts.
Essentially Free From
By the term “Essentially Free From” is intended for the purposes of the present invention, a soft tissue graft where the material removed (for example, cellular elements and infectious materials) from the soft tissue graft is not detectable using detection means known in the art at the time of filing of this application.
Normal Tissue
By the term “normal tissue” is intended for the purposes of the present invention, a particular soft tissue, for example a vein, artery, heart valve, ligament, tendon, fascia, dura mater, pericardium or skin, present in a living animal, including for example a human, a pig, and/or a cow. Tensile properties of a particular decellularized soft tissue graft approximate, that is, are not statistically significantly different from, the tensile properties of that tissue in a living animal. Cellular components of soft tissue graft biomaterials represent the major immunogenic component of such grafts post implantation.
Acellular Soft Tissue Graft
By the term “acellular tissue graft” is intended for the purposes of the present invention, soft tissue including but not limited to veins, arteries, heart valves, ligaments, tendons, fascia, dura matter, pericardium, and skin, from any mammalian source, including but not limited to, a human source, porcine source, and a bovine source, where the acellular graft produced is allogenic or xenogenic to the mammalian recipient.
The invention provides a process for removing these cellular components from the tissue without resultant damage to the matrix and/or tissue structure. Preferably, the tissue thickness does not exceed about 8 mm, more preferably does not exceed about 6 mm, and most preferably does not exceed about 4 mm, such that the time intervals described herein are sufficient for the process solutions to penetrate the tissue and solubilize the cellular components, allowing for the extraction of extractable materials. Processing times can be altered to accommodate thicker tissues. A quantity of endonuclease is used for a given volume of tissue, such that the quantity is sufficient to digest the DNA within that volume of tissue.
The invention recognizes that the mechanical strength of soft tissue graft biomaterials resides in the matrix structure of the graft. The matrix structure of these biomaterials include collagens, elastins, mucopolysaccharides and proteoglycan components. The removal of cellular components from the graft does not compromise the mechanical strength of the graft. The invention further recognizes that vascular and nonvascular soft tissue grafts do not need to be readily repopulated by recipient cells, post implantation, to function long-term. The absence of an early and rapid repopulation event(s) results in a graft having adequate mechanical strength similar to the mechanical strength associated with that particular normal tissue. This is because the subsequent remodeling of a graft is associated with weakening of the mechanical strength of the graft. That treatment of the graft with a strongly anionic detergent, such as sodium dodecylsulfate, leaves a strongly anionic charge distribution to the graft. This, in turn, restricts recellularization of the graft post implantation. Further, differences in anionic detergent binding to basement membrane components of the graft allows early re-endothelialization of vascular graft(s). That slow leaching of the anionic detergent from the graft allows slow long-term repopulation and slow long-term remodeling of the transplanted soft tissue graft consistent with a durability and graft life, to be measured in terms of decades. Although the description of the invention is directed primarily at processing vascular graft materials, it should be appreciated that this invention is not restricted to processing of vascular graft materials and can also be directed to processing non-vascular soft tissue grafts. Such tissue grafts include, but are not limited to, tissues such as tendons, fascia, ligaments, pericardium, intestine, skin, dura, and cartilage. Such soft tissue can be processed by one of ordinary skill in the art to which the present invention pertains by simple manipulation of the inventive processing times, without undue experimentation.
Tissue is processed according to the invention by surgically removing normal healthy tissues (for example, veins, arteries, heart valves) from animals or humans. The removed tissue is then transported to a processing facility where the tissue is cleaned of extraneous matter and quickly submersed in the first processing (extracting) solution which includes hypotonic buffered solutions containing an endonuclease, for example Benzonase®, and nonionic detergent(s) including for example Allowash Solution™, Triton X-100, and/or Tween 20, and MgCl 2 . Other suitable nonionic detergents can be readily selected and employed by one of ordinary skill in the art to which the present invention pertains, without undue experimentation. Procurement and transport of tissue is preferably carried out sterilely and is held in a sterile container on wet ice in a solution iso-osmolar to the cellular population of the tissue being procured and transported. Furthermore, antibiotics may be added to the procurement and transport solution. The invention includes the use of one or more decontaminating agents including for example one or more antibiotics, anti-fungal agents or anti-mycotic agents. Other such agents can be added during processing if so desired to maintain sterility of the procured tissues.
According to an aspect of the invention, a process for preparing biological material for implantation into a mammalian cardiovascular system, musculoskeletal system, or soft tissue system, or for recellularization in vitro, is provided and includes removing cellular membranes, nucleic acids, lipids, and cytoplasmic components, and forms an extracellular matrix including collagens, elastins, proteoglycans, and mucopolysaccharides, the process includes, isolating from a suitable donor a desired tissue sample of the biological material; extracting the tissue with mildly alkaline hypotonic buffered solution of an endonuclease (including for example Benzonase® (a registered product of Merck KGaA, Darmstadt, Germany)) and a nonionic detergent formulation (including for example Allowash Solution™ (a product of LifeNet, Virginia Beach, Va.)); treating the tissue with a mildly alkaline hypotonic buffered solution of an anionic detergent (including for example sodium dodecylsulfate); washing the tissue with water followed by a water or isotonic saline solution of chlorine dioxide or alcohol wash; and storage in a sealed container in water (for example, ultrapure water) or a dilute isotonic solution which may contain low concentrations of chlorine dioxide or 70% isopropanol.
The cellular components of soft tissue graft biomaterials represent the major immunogenic component of such grafts post implantation and the invention provides for the removal of these cellular components without resultant damage to the matrix structure in which the cells resided. Preferably, the soft tissue sample thickness does not exceed about 4 mm such that the time intervals described herein are sufficient for the solutions to penetrate and affect the necessary solubilization and extraction of extractable materials. The concentration of endonuclease utilized is based on calculations designed at achieving a sufficient quantity of endonuclease within a given volume of tissue which is sufficient to digest the DNA within that volume of tissue and is not arbitrarily chosen based on volume of processing solution. The inventive process maintains the mechanical strength of the soft tissue graft biomaterials because the process does not detrimentally affect the matrix structure of the graft. The matrix structure of these biomaterials include collagen, elastin, mucopolysaccharide and proteoglycan components.
The inventive process provides for the modulation of recellularization of the acellular soft tissue graft by adjusting the amount of bound and/or precipitated anionic detergent left in the acellular soft tissue graft produced.
This invention provides for the production of vascular and tendenous grafts, which are not repopulated by recipient cells, post implantation. The inventors discovered that these grafts do not need to be repopulated to function long-term. That absence of repopulation events reduce the possibility that subsequent remodeling of the graft will occur along with the weakening of mechanical strength of the graft which would be associated with remodeling. That treatment of the graft with a strongly anionic detergent, such as sodium dodecylsulfate, will leave a strongly anionic charge distribution to the graft that will restrict recellularization of the graft post implantation and that differences in SDS binding to the basement membrane components will allow reendothelialization of the vascular graft(s).
The inventors further discovered that the introduction of high salt concentrations in the tissues prior to or following treatment/extraction with an anionic detergent such as SDS results in the precipitation of greater quantities of this anionic detergent within the tissues and that this greater quantity of anionic detergent significantly restricts recellularization of the acellular tissue graft, than treatment of the tissue sample with an anionic detergent without the use of high salt concentrations in that tissue.
The invention provides a process that uses 0.001% to 0.024% anionic detergent, for example, SDS in the treatment phase which causes deposition of SDS in the tissues without the potentially harmful effects of using 1% SDS in the treatment phase and can be used preferentially with or without introduction of high salt concentrations in the tissue when recellularization of that tissue is desired. Although the description of this invention is directed primarily at processing vascular graft materials, it should be appreciated that this invention can also be directed to processing non vascular soft tissue grafts such as tendons, fascia, ligaments, pericardium, skin, dura, and cartilage by simple manipulation of processing times and parameters, such manipulation can be readily determined and employed by one of ordinary skill in the art, without undue experimentation.
In the inventive process, normal healthy vessels (veins, arteries, heart valves, tendons, ligaments, fascia, pericardium, intestine, urethra, etc.) are surgically removed from animals or humans, transported to the processing facility where they are cleaned of extraneous matter and immediately submersed in an extracting solution which contains a hypotonic buffered solution containing one or more endonucleases including for example, Benzonase, and one or more nonionic detergents including for example, Allowash Solution, Triton X-100, and Tween 20. In that most such vessels are procured at sites distant from the processing facility and that such vessels may ultimately either be cryopreserved or made acellular, procurement and transport will normally be in a sterile container on wet ice in a solution isoosmolar to the cellular population of the tissue being procured and transported. Furthermore, antibiotics are preferably added to the procurement and transport solution. One or more decontaminating agents, including for example, one or more antibiotics, can be optionally employed in any step of the inventive process, to maintain sterility of the procured tissues.
FIG. 1 illustrates the processing of a long vein grafts ( 1 ), the distal end of the vein is cannulated onto the ribbed attachment ( 2 ) of the inlet port ( 3 ) and a single suture ( 4 ) is used to secure the vein. An additional suture line ( 5 ) is attached to the proximal end of the vein for later use in maintaining the vein in an extended state in the processing vessel ( 6 ). The vein ( 1 ) is then removed from the first processing (extracting) solution and transferred to the processing vessel ( 6 ) that has been temporarily inverted. The second suture line ( 5 ) along with the vein ( 1 ) is passed through the processing vessel ( 6 ) and secured to a point ( 7 ) on the outlet port end ( 8 ) of the processing vessel ( 6 ). Prior to closing the processing vessel, a portion of the first processing (extracting) solution is gently added to the processing vessel and the inlet port ( 3 ), with attached vein ( 1 ), is then secured. The processing vessel ( 6 ) is turned such that the inlet port ( 3 ) is down and the outlet port ( 8 ) is up and the vessel ( 6 ) is attached to its support racking system via clamps ( 9 ). Sterile disposable tubing ( 10 ) is attached to the inlet port ( 3 ) and to pump tubing in a peristaltic pump ( 11 ). Further, sterile disposable tubing ( 12 ) is attached to the inflow side ( 13 ) of the peristaltic pump ( 11 ) and to the solution reservoir ( 14 ) which will contain all remaining first processing (extracting) solution. Finally, sterile disposable tubing ( 15 ) is attached between the top (outlet) port ( 8 ) of the processing vessel ( 6 ) and the solution reservoir ( 14 ). Sterile, in-line, filters ( 16 ) can optionally be added at appropriate positions in the fluid flow to safeguard sterility during processing. The first processing (extracting) solution is pumped into, through and out of the processing vessel ( 6 ) such that flow of fluids through the luminal part of the vein tubule passes into the processing vessel ( 6 ) to affect constant solution change in the processing vessel and out through the outlet port ( 8 ) to a solution reservoir ( 14 ). By processing the vein in an inverted state, air which may be trapped in the luminal space of the vein will be induced to exit facilitating equal access of the processing solutions to the vein tissue being processed. Processing of the vein tissue with the first processing (extracting) solution is preferably carried out at temperatures ranging from about 4° C. to about 37° C. for time periods ranging from about one hour to about 24 hours (overnight as necessary to accommodate processing scheduling of processing staff). The endonuclease (Benzonase) is optimally active between pH 6 and 10, and from 0° C. to above 42° C. (Merck literature describing product) when provided with 1-2 mM Mg +2 . Following processing with the first processing (extracting) solution, the first processing solution can optionally be replaced with water, for example sterile ultrapure water, to preclude a possible precipitation reaction between the nonionic detergents in the first processing (extracting) solution and the anionic detergent in the second processing (treating) solution, or the first processing (extracting) solution can be replaced with an alkaline hypotonic solution containing one or more detergents, including for example, sodium dodecylsulfate (SDS) at a concentration, for example, of about 1% by weight (second processing (treating) solution). Under the optional processing procedure, only sufficient water need be circulated through the processing vessel to affect one volume change of solution in the processing vessel. During processing with the second processing (treating) solution, this solution is circulated through the tissue, preferably at a temperature of from room temperature to about 37° C., to avoid precipitation of the detergent, for example SDS, at reduced temperatures, for a time period not shorter than 3 hours. Following processing with the second processing (treating) solution, water, for example ultrapure sterile water, is circulated through the tissue and processing vessel such that the available volume of washing solution approximates a 1000-fold dilution of the detergent, for example SDS, present in the second processing (treating) solution. The SDS will exit from the tissues to a given amount of SDS/mg tissue wet weight (protein concentration) provided the washing time is at least 1 hour, preferably at least 2 hours and more preferably at least 3 hours, at a flow rate sufficient to affect a volume change in the processing vessel about every 30-40 minutes, suitable flow rates including for example of from about 30 mls/min. to about 70 mls/min., more preferably from about 40 mls/min to about 60 mls/min., and most preferably about 50 mls/min. Following washing in this final processing step, the vein is removed from the processing vessel and transferred into storage solution, for example phosphate buffered saline, 70% isopropanol, or 0.001% to 0.005% chlorine dioxide in sterile ultrapure water/isotonic saline, and packaged in a volume of storage solution sufficient to cover the tissue preventing dehydration. This packaged graft may then be terminally sterilized, for example using gamma irradiation, if so desired. Artery segments can be similarly processed, taking into consideration that veins have valves and arteries do not, and that veins generally have a smaller internal diameter than arteries, thus dictating slower flow rates with veins.
FIG. 2 illustrates processing heart valve grafts. The heart valve ( 1 ) is placed into the deformable processing device ( 6 ') such that the valved end of the conduit is directed towards the inlet port ( 3 ) and the nonvalved end of the conduit is directed towards the outlet port ( 8 ). Prior to closing the processing vessel ( 6 '), a portion of the first processing (extracting) solution is gently added to the processing vessel. The processing vessel ( 6 ') is turned such that the inlet port ( 3 ) is down and the outlet port ( 8 ) is up to effect removal of air bubbles, and the vessel ( 6 ') attached to its support racking system via clamps ( 9 ). Sterile disposable tubing ( 10 ) is attached to the inlet port ( 3 ) and to pump tubing in a peristaltic pump ( 11 ). Further, sterile disposable tubing ( 12 ) is attached to the inflow side ( 13 ) of the peristaltic pump ( 11 ) and to the solution reservoir ( 14 ) which will contain all remaining first processing (extracting) solution. Finally, sterile disposable tubing ( 15 ) is attached between the top (outlet) port ( 8 ) of the processing vessel ( 6 ') and the solution reservoir ( 14 ). Sterile, in-line, filters ( 16 ) can optionally be added at appropriate positions in the fluid flow to safeguard sterility during processing. The first processing (extracting) solution is pumped into, through and out of the processing vessel ( 6 ') such that the flow of fluids through the luminal part of the heart valve ( 1 ) passes into the processing vessel ( 6 ') to affect constant solution change in the processing vessel ( 6 ') and out through the outlet port ( 8 ) to a solution reservoir ( 14 ). By processing the heart valve ( 1 ) in this orientation, air which may be trapped in the luminal space of the valve will be induced to exit facilitating equal access of the processing solutions to the valve tissue being processed. Processing of the heart valve ( 1 ) tissue with the first processing (extracting) solution is performed at for example, a temperature of from about 4° C. to about 37° C., for example for time periods of from about one hour to about 24 hours (overnight as necessary to accommodate processing scheduling of processing staff). The endonuclease (Benzonase) is optimally active between pH 6 and 10, and from 0° C. to above 42° C. (Merck literature describing product) when provided with 1-2 mM Mg +2 . Following processing with the first processing (extracting) solution, the first processing (extracting) solution is optionally be replaced with water, for example sterile ultrapure water, to preclude a possible precipitation reaction between the nonionic detergents in the first processing (extracting) solution and the anionic detergent in the second processing (treating) solution, or the first processing (extracting) solution can be replaced with an alkaline hypotonic solution containing for example, about 1% by weight of a detergent, for example, sodium dodecylsulfate (SDS) (second processing (treating) solution). Under the optional processing procedure, only sufficient water need be circulated through the processing vessel to affect one volume change of solution in the processing vessel. The second processing (treating) solution is circulated through the tissue at a temperature for example, of from about room temperature to about 37° C., to avoid precipitation of the detergent, for example SDS, at reduced temperatures, for a time period of for example, not shorter than 3 hours. Following processing with the second processing (treating) solution, water, for example ultrapure sterile water, is circulated through the tissue and processing vessel such that the available volume of washing solution approximates a 1000-fold dilution of the SDS present in the second processing (treating) solution. The SDS will exit from the tissues to a given amount of SDS/mg tissue wet weight (protein concentration) provided the washing time preferably exceeds 1 hour, more preferably exceeds 2 hours, and most preferably exceeds about 3 hours, at a flow rate sufficient to affect a volume change in the processing vessel about every 30-40 minutes, suitable flow rates including for example of from about 30 mls/min. to about 70 mls/min., more preferably from about 40 mls/min to about 60 mls/min., and most preferably about 50 mls/min. Following washing, the heart valve may then be removed from the processing vessel and transferred into storage solution of for example, either 70% isopropanol or 0.001% chlorine dioxide in sterile ultrapure water, and packaged in a volume of storage solution sufficient to cover the tissue preventing dehydration. Alternatively, the storage solutions can be pumped into the processing vessel until the water wash solution has been adequately exchanged and the whole processing vessel sealed and used as the storage container for distribution.
For all other soft tissue grafts, the tissue is placed into the deformable processing device such that the smaller portion is directed towards the inlet port and the larger (bulkier) end of the tissue is directed towards the outlet port. Preferably the thickness of other soft tissue grafts does not exceed about 8 mm, more preferable does not exceed 5 mm, and most preferably the thickness does not exceed about 2-3 mm. If the thickness of the tissue graft exceeds about 5 mm, incubation and processing times need to be appropriately extended. Such incubation and processing times can be readily selected and employed by one of ordinary skill in the art to which the present invention pertains based on the thickness of the tissue being processed, the type of tissue being processed, and the volume of tissue being processed, without undue experimentation. Prior to closing the processing vessel, a portion of the first processing (extracting) solution is gently added to the processing vessel. The processing vessel is then turned such that the inlet port is down and the outlet port is up and the vessel is attached to its support racking system for example, via clamps. Sterile disposable tubing is attached to the inlet port and to pump tubing in a peristaltic pump. Further, sterile disposable tubing is attached to the inflow side of the peristaltic pump and to the solution reservoir which will contain all remaining first processing (extracting) solution. Finally, sterile disposable tubing is attached between the top (outlet) port of the processing vessel and the solution reservoir. Sterile, in-line, filters can optionally be added at appropriate positions in the fluid flow to safeguard sterility during processing. The first processing (extracting) solution is pumped into, through and out of the processing vessel such that flow of fluids occurs in close proximity to the surfaces of the soft tissue grafts into the processing vessel to affect constant solution change in the processing vessel and out through the outlet port to a solution reservoir. By processing the soft tissue graft in this orientation, the bulkier portions of the soft tissue graft will receive the greatest flow of fluids across the surfaces facilitating equal access of the processing solutions to the tissue being processed. Processing of the soft tissue graft with the first processing (extracting) solution is preferably performed at a temperature of from about 4° C. to about 37° C., for a period of time preferably of from about one hour to about 24 hours (overnight as necessary to accommodate processing scheduling of processing staff). The endonuclease (Benzonase) is optimally active between pH 6 and 10, and from 0° C. to above 42° C. (Merck literature describing product) when provided with 1-2 mM Mg +2 . Following processing with the first processing (extracting) solution, the first processing (extracting) solution is optionally be replaced with water, for example sterile ultrapure water, to preclude a possible precipitation reaction between the nonionic detergents in the first processing (extracting) solution and the anionic detergent in the second processing solution, or the first processing (extracting) solution can be replaced with an alkaline hypotonic solution containing for example, preferably about 1% by weight of a detergent, for example, preferably sodium dodecylsulfate (SDS) (second processing (treating) solution). Under the optional processing procedure, only sufficient water need be circulated through the processing vessel to affect one volume change of solution in the processing vessel. The second processing (treating) solution is circulated through and/or around the tissue at a temperature of preferably form room temperature to about 37° C., to avoid precipitation of the detergent, for example SDS, at reduced temperatures, for a time period of preferably not shorter than 3 hours. Following processing with the second processing (treating) solution, water for example ultrapure sterile water, is circulated through and/or around the tissue and processing vessel such that the available volume of washing solution approximates a 1000-fold dilution of the SDS present in the second processing (treating) solution. The SDS will exit from the tissues to a given amount of SDS/mg tissue wet weight (protein concentration) provided the washing time preferably exceeds 1 hour, more preferably exceeds 2 hours and most preferably exceeds 3 hours, at a flow rate sufficient to affect a volume change in the processing vessel about every 30-40 minutes, suitable flow rates including for example of from about 30 mls/min. to about 70 mls/min., more preferably from about 40 mls/min to about 60 mls/min., and most preferably about 50 mls/min. Following washing, the soft tissue graft may be removed from the processing vessel and transferred into storage solution containing for example, buffered isotonic saline, 70% isopropanol, or 0.001% to 0.005% chlorine dioxide in sterile ultrapure water/isotonic saline, and packaged in a volume of storage solution sufficient to cover the tissue preventing dehydration. Alternatively, the storage solutions can be pumped into the processing vessel until the ultrapure water wash solution has been adequately exchanged and the whole processing vessel sealed, sterilized for example using gamma-irradiation, and used as the storage container for distribution. Storage of processed soft tissue grafts should be in a solution which covers the graft and which is contained in a container that will prevent evaporation and fluid loss or concentration of solutes. The solution can be isotonic saline, isotonic saline or ultrapure water containing a preservative such as chlorine dioxide, isopropanol, METHYLPARABIN® (Croda, Inc.), antibiotics, antimicrobials, antimycotic agents, antifungal agents, or ultrapure water, or similar bacteriostatic or bacteriocidal agent which do not chemically alter the matrix components of the soft tissue grafts. Suitable storage solutions are well known to of ordinary skill in the art to which the present invention applies, and such solutions can be readily selected and employed by those of ordinary skill in the art to which the present invention applies without undue experimentation. The storage containers with solution and soft tissue grafts can be terminally sterilized, for example using gamma irradiation at doses up to 2.5 Mrads.
The following examples illustrate processing of soft tissue grafts according to the invention.
EXAMPLE 1
Saphenous vein tissues (two) from each leg of an acceptable human donor were carefully dissected under sterile conditions to remove all visible fat deposits and the side vessels were tied off using nonresorbable suture materials such that the ties did not occur in close proximity to the long run of the vessel. Sutures can restrict the decellularization process and the tissues under the sutures were removed following decellularization. For long vein grafts (40-60 cm) (FIG. 1 ), the distal ends of the veins were cannulated onto the ribbed attachment of the inlet port(s) and single sutures used to secure each vein. Additional suture lines were attached to the proximal ends of the veins. The veins were then removed from the dissecting solution (ultrapure water containing 50 mM Tris-HCl (pH 7.2), 5 mM EDTA, and one or more antibiotics) and transferred to the processing vessel which had been temporarily inverted. The second suture line along with the vein was passed through the processing vessel and secured to a point on the outlet port end of the processing vessel. Prior to closing the processing vessel, a portion of the first processing solution was gently added to the processing vessel and the inlet port, with attached vein, was then secured. The processing vessel was then turned such that the inlet port was down and the outlet port was up and the vessel attached to its support racking system via clamps. Sterile disposable tubing was attached to the inlet port and to pump tubing in a peristaltic pump. Further, sterile disposable tubing was attached to the inflow side of the peristaltic pump and to the solution reservoir which contained all remaining first processing solution. Total processing solution volume approximated 250 ml. Finally, sterile disposable tubing was attached between the top (outlet) port of the processing vessel and the solution reservoir. Sterile, in-line, filters were added at appropriate positions in the fluid flow to safeguard sterility during processing. The first processing solution was then pumped into, through and out of the processing vessel such that flow of fluids through the luminal part of the vein tubule passed into the processing vessel to affect constant solution change in the processing vessel and out through the outlet port to a solution reservoir. By processing the vein in an inverted state, air which had been “trapped” in the luminal space of the vein was induced to exit facilitating equal access of the processing solutions to the vein tissue being processed. Processing of the vein tissue with the first processing solution was performed at 25±5° C. for 16 hours using a flow rate of the first processing solution of 60 mls/min. The first processing (extracting) solution consisted of 50 mM Tris-HCl (pH 7.2), 5 mM MgCl 2 , 1% (w:v) Allowash Solution (as described in U.S. Pat. No. 5,556,379), and endonuclease (Benzonase, a registered product of EM Industries, Inc.) (41.8 Units/ml). Following processing with the first processing solution, the first processing solution was replaced with sterile ultrapure water (250 mls at a pump rate of 90 mls/min.) which was then replaced with an alkaline hypotonic solution containing about 1% by weight sodium dodecylsulfate (SDS) in ultrapure water buffered with 50 mM Tris-HCl (pH 7.2) (second processing (treating) solution). Under this processing procedure, only sufficient ultrapure water was circulated through the processing vessel to affect one volume change of solution in the processing vessel. Under the processing with second processing (treating) solution, this second solution was circulated (flow rate of 60 mls/min.) through the tissue at room temperature (25±5° C.), to avoid precipitation of the SDS at reduced temperatures, for a time period of about 3 hours. Following processing with the second processing solution, ultrapure sterile water was circulated through the tissue and processing vessel such that the available volume of washing solution approximated a 1000-fold dilution of the SDS present in the second processing solution with a flow rate of 2 ml/min. for 1.5 hours. Following washing in this final processing step, the vein was removed from the processing vessel and transferred into storage solution of 0.005% chlorine dioxide in sterile ultrapure water and packaged in a volume of this solution sufficient to cover the tissue.
EXAMPLE 2
Saphenous vein tissues (two) from each leg of an acceptable human donor were carefully dissected under sterile conditions to remove all visible fat deposits and side vessels were tied off using nonresorbable suture materials such that the ties did not occur in close proximity to the long run of the vessel. Sutures can restrict the decellularization process and the tissues under the sutures were removed following decellularization. For these long vein grafts (33 and 28 cm) (FIG. 1 ), the distal ends of the veins were cannulated onto the ribbed attachment of the inlet port(s) and single sutures used to secure each vein. Additional suture lines were attached to the proximal ends of the veins. At this point, the veins were removed from the dissecting solution (ultrapure water containing 50 mM Tris-HCl (pH 7.2), 5 mM EDTA, and one or more antibiotics and transferred to the processing vessel which had been temporarily inverted. The second suture line along with the vein was passed through the processing vessel and secured to a point on the outlet port end of the processing vessel. Prior to closing the processing vessel, a portion of the first processing (extracting) solution was gently added to the processing vessel and the inlet port, with attached vein, was then secured. The processing vessel was then turned such that the inlet port was down and the outlet port was up and the vessel attached to its support racking system via clamps. Sterile disposable tubing was attached to the inlet port and to pump tubing in a peristaltic pump. Further, sterile disposable tubing was attached to the inflow side of the peristaltic pump and to the solution reservoir which contained all remaining first processing (extracting) solution. Total processing solution volume approximated 250 ml. Finally, sterile disposable tubing was attached between the top (outlet) port of the processing vessel and the solution reservoir. Sterile, in-line, filters were added at appropriate positions in the fluid flow to safeguard sterility during processing. The first processing (extracting) solution was pumped into, through and out of the processing vessel such that flow of fluids through the luminal part of the vein tubule passed into the processing vessel to affect constant solution change in the processing vessel and out through the outlet port to a solution reservoir. By processing the vein in an inverted state, air which had been “trapped” in the luminal space of the vein was induced to exit facilitating equal access of the processing solutions to the vein tissue being processed. Processing of the vein tissue with the first processing (extracting) solution was performed at 25±5° C. for 16 hours using a flow rate of the first processing solution of 30 mls/min. The first processing (treating) solution consisted of 50 mM Tris-HCl (pH 7.2), 5 MM MgCl 2 , 1% (w:v) Triton X-100, and endonuclease (Benzonase, a registered product of EM Industries, Inc.) (41.8 Units/ml). Following processing with the first processing (extracting) solution, the first processing (extracting) solution was replaced with an alkaline hypotonic solution containing about 1% by weight sodium dodecylsulfate (SDS) in ultrapure water buffered with 50 mM Tris-HCl (pH 7.2) (second processing (treating) solution). Under the processing with second processing (treating) solution, this second solution was circulated (flow rate of 120 mls/min.) through the tissue at room temperature (25±5° C.), to avoid precipitation of the SDS at reduced temperatures, for a time period of 3 hours. Following processing with the second processing solution, ultrapure sterile water was circulated through the tissue and processing vessel such that the available volume of washing solution approximated a 1000-fold dilution of the SDS present in the second processing solution with a flow rate of 1 ml/minute for 1.5 hours. Following washing in this final processing step, the vein was removed from the processing vessel and transferred into storage solution of 0.001% chlorine dioxide in sterile ultrapure water and packaged in a volume of this solution sufficient to cover the tissue.
EXAMPLE 3
Internal mammary artery tissues (two) from an acceptable human donor were carefully dissected under sterile conditions to remove all visible fat deposits and side vessels were tied off using nonresorbable suture materials such that the ties did not occur in close proximity to the long run of the vessel. Sutures can restrict the decellularization process and the tissues under the sutures were removed following decellularization. For short artery grafts (11 and 8 cm) (FIG. 1 ), one end of each artery were cannulated onto the ribbed attachment of the inlet port(s) and single sutures used to secure each arteries. The arteries were then removed from the dissecting solution (ultrapure water containing 50 mM Tris-HCl (pH 7.2), 5 mM EDTA, and one or more antibiotics) and transferred to the processing vessel which had been temporarily inverted. Prior to closing the processing vessel, a portion of the first processing (extracting) solution was gently added to the processing vessel and the inlet port, with attached artery, was then secured. At this point, the processing vessel was turned such that the inlet port was down and the outlet port was up and the vessel attached to its support racking system via clamps. Sterile disposable tubing was attached to the inlet port and to pump tubing in a peristaltic pump. Further, sterile disposable tubing was attached to the inflow side of the peristaltic pump and to the solution reservoir which contained all remaining first processing solution. Total processing solution volume approximated 150 ml. Finally, sterile disposable tubing was attached between the top (outlet) port of the processing vessel and the solution reservoir. Sterile, in-line, filters were added at appropriate positions in the fluid flow to safeguard sterility during processing. The first processing (extracting) solution was pumped into, through and out of the processing vessel such that flow of fluids through the luminal part of the artery tubule passed into the processing vessel to affect constant solution change in the processing vessel and out through the outlet port to a solution reservoir. By processing the artery in an inverted state, air which had been “trapped” in the luminal space of the vein was induced to exit facilitating equal access of the processing solutions to the vein tissue being processed. Processing of the artery tissue with the first processing (extracting) solution was performed at 25±5° C. for 16 hours using a flow rate of the first processing (extracting) solution of 50 mls/min. The first processing (extracting) solution consisted of 50 mM Tris-HCl (pH 7.2), 5 mM MgCl 2 , 1% (w:v) Allowash Solution (as described in U.S. Pat. No. 5,556,379), and endonuclease (Benzonase, a registered product of EM Industries, Inc.) (41.8 Units/ml). Following processing with the first processing (extracting) solution, the first processing (extracting) solution was replaced with sterile ultrapure water (250 mls at a pump rate of 60 mls/min.) which was then replaced with an alkaline hypotonic solution containing about 1% by weight sodium dodecylsulfate (SDS) in ultrapure water buffered with 50 mM Tris-HCl (pH 7.2) (second processing (treating) solution). Under this processing procedure, only sufficient ultrapure water was circulated through the processing vessel to affect one volume change of solution in the processing vessel. Under the processing with second processing solution, this second solution was circulated (flow rate of 30 mls/min.) through the tissue at room temperature (25±5° C.), to avoid precipitation of the SDS at reduced temperatures, for a time period of 3 hours. Following processing with the second processing solution, ultrapure sterile water was circulated through the tissue and processing vessel such that the available volume of washing solution approximated a 1000-fold dilution of the SDS present in the second processing solution with a flow rate of 2 ml/min. for 1.5 hours. Following washing in this final processing step, the artery was removed from the processing vessel and transferred into storage solution of 70% (v:v) pharmaceutical grade isopropanol in sterile ultrapure water and packaged in a volume of this solution sufficient to cover the tissue.
EXAMPLE 4
Aortic and pulmonary tissues (one each) from a heart of an acceptable human donor were carefully dissected under sterile conditions to remove all visible fat deposits and cardiac muscle tissue (leaving only a small but visible band of cardiac muscle tissue around the proximal end of the conduit. The valves were then removed from the dissecting solution (ultrapure water containing 50 mM Tris-HCl (pH 7.2), 5 mM EDTA, and one or more antibiotics) and transferred to the deformable (plastic) processing vessel (FIG. 2 ). Prior to closing the processing vessel, a portion of the first processing (extracting) solution was gently added to the processing vessel and the side access port closed using the clamping mechanism illustrated in FIG. 2 . The proximal end of the heart valve(s) was placed towards the inlet port and the distal end(s) of the valve was placed towards the outlet port. At this point, the processing vessel was placed such that the inlet port was down and the outlet port was up and the vessel attached to its support racking system via clamps. Sterile disposable tubing was attached to the inlet port and to pump tubing in a peristaltic pump. Further, sterile disposable tubing was attached to the inflow side of the peristaltic pump and to the solution reservoir which contained all remaining first processing solution. Total processing solution volume approximated 350 ml. Finally, sterile disposable tubing was attached between the top (outlet) port of the processing vessel and the solution reservoir. Sterile, in-line, filters were added at appropriate positions in the fluid flow to safeguard sterility during processing. The first processing (extracting) solution was pumped into, through and out of the processing vessel such that flow of fluids through the luminal part of the heart valve tubule passed into the processing vessel to affect constant solution change in the processing vessel and out through the outlet port to a solution reservoir. By processing the heart valve in an noninverted state, air which had been “trapped” in the luminal spaces behind the leaflets of the heart valve was induced to exit facilitating equal access of the processing solutions to the heart valve tissue being processed. Processing of the valve and conduit tissue with the first processing (extracting) solution was performed at 25±5° C. for 16 hours using a flow rate of the first processing (extracting) solution of 50 mls/min. The first processing (extracting) solution consisted of 50 mM Tris-HCl (pH 7.2), 5 MM MgCl 2 , 1% (w:v) Allowash Solution (as described in U.S. Pat. No. 5,556,379), and endonuclease (Benzonase, a registered product of EM Industries, Inc.) (41.8 Units/ml). Following processing with the first processing (extracting) solution, the first processing (extracting) solution was replaced with sterile ultrapure water (350 mls at a pump rate of 50 mls/min.) which was then replaced with an alkaline hypotonic solution containing about 1% by weight sodium dodecylsulfate (SDS) in ultrapure water buffered with 50 mM Tris-HCl (pH 7.2) (second processing (treating) solution). Under this processing procedure, only sufficient ultrapure water was circulated through the processing vessel to affect one volume change of solution in the processing vessel. Under the processing with second processing (treating) solution, this second solution was circulated (flow rate of 30 mls/min.) through the tissue at room temperature (25±5° C.), to avoid precipitation of the SDS at reduced temperatures, for a time period of 5 hours. Following processing with the second processing solution, ultrapure sterile water was circulated through the tissue and processing vessel such that the available volume of washing solution approximated a 1000-fold dilution of the SDS present in the second processing solution with a flow rate of 1 ml/min. for 1.5 hours. Following washing in this final processing step, the heart valve(s) was (were) removed from the processing vessel and transferred into storage solution of 0.05% chlorine dioxide in sterile ultrapure water and packaged in a volume of this solution sufficient to cover the tissue.
EXAMPLE 5
Saphenous vein tissues (two) from each leg of an acceptable human donor were carefully dissected under sterile conditions to remove all visible fat deposits and side vessels were tied off using nonresorbable suture materials such that the ties did not occur in close proximity to the long run of the vessel. Sutures can restrict the decellularization process and the tissues under the sutures were removed following decellularization. For long vein grafts (40-60 cm) (FIG. 1 ), the distal ends of the veins were cannulated onto the ribbed attachment of the inlet port(s) and single sutures used to secure each vein. Additional suture lines were attached to the proximal ends of the veins. The veins were then removed from the dissecting solution (ultrapure water containing 50 mM Tris-HCl (pH 7.2), 5 mM EDTA, and one or more antibiotics) and transferred to the processing vessel which had been temporarily inverted. The second suture line along with the vein was passed through the processing vessel and secured to a point on the outlet port end of the processing vessel. Prior to closing the processing vessel, a portion of the first processing (extracting) solution was gently added to the processing vessel and the inlet port, with attached vein, was then secured. At this point, the processing vessel was turned such that the inlet port was down and the outlet port was up and the vessel attached to its support racking system via clamps. Sterile disposable tubing was attached to the inlet port and to pump tubing in a peristaltic pump. Further, sterile disposable tubing was attached to the inflow side of the peristaltic pump and to the solution reservoir which contained all remaining first processing solution. Total processing solution volume approximated 250 ml. Finally, sterile disposable tubing was attached between the top (outlet) port of the processing vessel and the solution reservoir. Sterile, in-line, filters were added at appropriate positions in the fluid flow to safeguard sterility during processing. The first processing (extracting) solution was pumped into, through and out of the processing vessel such that flow of fluids through the luminal part of the vein tubule passed into the processing vessel to affect constant solution change in the processing vessel and out through the outlet port to a solution reservoir. By processing the vein in an inverted state, air which had been “trapped” in the luminal space of the vein was induced to exit facilitating equal access of the processing solutions to the vein tissue being processed. Processing of the vein tissue with the first processing (extracting) solution was performed at 25±5° C. for 18 hours using a flow rate of the first processing (extracting) solution of 30 mls/min. The first processing (extracting) solution consisted of 50 mM Tris-HCl (pH 7.2), 5 mM MgCl 2 , 1% (w:v) Allowash Solution (as described in U.S. Pat. No. 5,556,379), and endonuclease (Benzonase, a registered product of EM Industries, Inc.) (41.8 Units/ml). Following processing with the first processing (extracting) solution, the first processing (extracting) solution was replaced with sterile ultrapure water (250 mls at a pump rate of 30 mls/min.) which was then replaced with an alkaline hypotonic solution containing about 1% by weight sodium dodecylsulfate (SDS) in ultrapure water buffered with 50 mM Tris-HCl (pH 7.2) (second processing (treating) solution). Under this processing procedure, only sufficient ultrapure water was circulated through the processing vessel to affect one volume change of solution in the processing vessel. Under the processing with second processing solution, this second solution was circulated (flow rate of 30 mls/min.) through the tissue at room temperature (25±5° C.), to avoid precipitation of the SDS at reduced temperatures, for a time period of than 1.5 hours. Following processing with the second processing solution, ultrapure sterile water was circulated through the tissue and processing vessel such that the available volume of washing solution approximated a 1000-fold dilution of the SDS present in the second processing (treating) solution with a flow rate of 1 ml/min. for 6 hours. Following washing in this final processing step, the vein was removed from the processing vessel and transferred into storage solution of isotonic saline in sterile ultrapure water and packaged in a volume of this solution sufficient to cover the tissue. The packaged tissue was gamma-radiation sterilized at 2.5 Mrads and stored at room temperature until use.
EXAMPLE 6
Saphenous vein tissues (two) from each leg of an acceptable human donor were carefully dissected under sterile conditions to remove all visible fat deposits and side vessels tied off using nonresorbable suture materials such that the ties did not occur in close proximity to the long run of the vessel. Sutures can restrict the decellularization process and the tissues under the sutures will be removed following decellularization. For long vein grafts (40-60 cm) (FIG. 1 ), the distal ends of the veins were cannulated onto the ribbed attachment of the inlet port(s) and single sutures used to secure each vein. Additional suture lines were attached to the proximal ends of the veins. At this point, the veins were removed from the dissecting solution (ultrapure water containing 50 mM Tris-HCl (pH 7.2), 5 mM EDTA, and antibiotic solution for cardiovascular tissue procurement and transport) and transferred to the processing vessel(s) which had been temporarily inverted. The second suture line along with the vein was passed through the processing vessel and secured to a point on the outlet port end of the processing vessel. Prior to closing the processing vessel, a portion of the First Processing Solution was gently added to the processing vessel and the inlet port, with attached vein, was then secured. At this point, the processing vessel was turned such that the inlet port was down and the outlet port was up and the vessel attached to its support racking system via clamps, respectively. Sterile disposable tubing was attached to the inlet port and to pump tubing in a peristaltic pump. Further, sterile disposable tubing was attached to the inflow side of the peristaltic pump and to the solution reservoir which contained all remaining first processing solution. Total processing solution volume approximated 250 ml. Finally, sterile disposable tubing was attached between the top (outlet) port of the processing vessel and the solution reservoir. Sterile, in-line, filters were added at appropriate positions in the fluid flow to safeguard sterility during processing. First Processing Solution was pumped into, through and out of the processing vessel such that flow of fluids through the luminal part of the vein tubule passed into the processing vessel to affect constant solution change in the processing vessel and out through the outlet port to a solution reservoir. By processing the vein in an inverted state, air which had been “trapped” in the luminal space of the vein was induced to exit facilitating equal access of the processing solutions to the vein tissue being processed. Processing of the vein tissue with the First Processing Solution was performed at temperatures approximating 25±5° C. for 16 hours using a flow rate of the First Processing Solution of 50 mls/min. The First Processing Solution consisted of 50 mM Tris-HCl (pH 8), 2 mM MgCl 2 , 1% (w:v) Allowash Solution (as described in U.S. Pat. No. 5,556,379), and endonuclease (Benzonase, a registered product of EM Industries, Inc.) (41.8 Units/ml). Following processing with the First Processing Solution, the First Processing Solution was replaced with sterile ultrapure water containing 0.5 M NaCl (250 mls at a pump rate of 50 mls/min.) over a period of 1 hour, which was then replaced with an alkaline hypotonic solution containing about 0.001% by weight sodium dodecylsulfate (SDS) in ultrapure water buffered with 50 mM Tris-HCl (pH 9) (Second Processing Solution). Under this processing procedure, only sufficient ultrapure water salt solution needed to be circulated through the processing vessel to affect one volume change of solution in the processing vessel. Under the processing with Second Processing Solution, this second solution was circulated (flow rate of 50 mls/min.) through the tissue at room temperature (25±5° C.), to allow precipitation of the SDS at reduced temperatures, for a time period of than 3 hours. Following processing with the Second Processing Solution, ultrapure sterile water containing 0.01 M calcium chloride was circulated through the tissue and processing vessel such that the available volume of washing solution approximated a 1000-fold dilution of the SDS present in the Second Processing Solution with a flow rate of 50 ml/min. for 1.5 hours. Following washing in this final processing step, the vein was removed from the processing vessel and transferred into storage solution of 0.001% chlorine dioxide in sterile ultrapure water and packaged in a volume of this solution sufficient to cover the tissue.
EXAMPLE 7
Saphenous vein tissues (two) from each leg of an acceptable human donor were carefully dissected under sterile conditions to remove all visible fat deposits and side vessels tied off using nonresorbable suture materials such that the ties did not occur in close proximity to the long run of the vessel. Sutures can restrict the decellularization process and the tissues under the sutures will be removed following decellularization. For these long vein grafts (33 and 28 cm) (FIG. 1 ), the distal ends of the veins were cannulated onto the ribbed attachment of the inlet port(s) and single sutures used to secure each vein. Additional suture lines were attached to the proximal ends of the veins. At this point, the veins were removed from the dissecting solution (ultrapure water and antibiotic solution including: 100 mcg/ml polymyxin B sulfate, 240 mcg/ml cefoxitin, 50 mcg/ml vancomycin, 120 mcg/ml lincomycin HCL, (for use with heart valves and arteries, when veins are processed, 0.12 mg/ml papaverive is added) in RMI1640 tissue culture media, and transferred to the processing vessel(s) which had been temporarily inverted. The second suture line along with the vein was passed through the processing vessel and secured to a point on the outlet port end of the processing vessel. Prior to closing the processing vessel, a portion of the First Processing Solution was gently added to the processing vessel and the inlet port, with attached vein, was then secured. At this point, the processing vessel was turned such that the inlet port was down and the outlet port was up and the vessel attached to its support racking system via clamps, respectively. Sterile disposable tubing was attached to the inlet port and to pump tubing in a peristaltic pump. Further, sterile disposable tubing was attached to the inflow side of the peristaltic pump and to the solution reservoir which contained all remaining first processing solution. Total processing solution volume approximated 250 ml. Finally, sterile disposable tubing was attached between the top (outlet) port of the processing vessel and the solution reservoir. Sterile, in-line, filters were optionally added at appropriate positions in the fluid flow to safeguard sterility during processing. First Processing Solution was pumped into, through and out of the processing vessel such that flow of fluids through the luminal part of the vein tubule passed into the processing vessel to affect constant solution change in the processing vessel and out through the outlet port to a solution reservoir. By processing the vein in an inverted state, air which had been “trapped” in the luminal space of the vein was induced to exit facilitating equal access of the processing solutions to the vein tissue being processed. Processing of the vein tissue with the First Processing Solution was performed at temperatures ranging between 25±5° C. for 16 hours using a flow rate of the First Processing Solution of 50 mls/minute. The First Processing Solution consisted of 50 mM Tris-HCl (pH 8), 2 MM MgCl 2 , 1% (w:v) Triton X-100, and endonuclease (Benzonase, a registered product of EM Industries, Inc.) (41.8 Units/ml). Following processing with the First Processing Solution, the First Processing Solution was replaced with a sterile water solution of 1.0 M KCl (50 mls/min. flow rate over 1.5 hours) and then by an alkaline hypotonic solution containing about 1% by weight sodium dodecylsulfate (SDS) in ultrapure water buffered with 50 mM Tris-HCl (pH 9) (Second Processing Solution). Under the processing with Second Processing Solution, this second solution was circulated (flow rate of 50 mls/min.) through the tissue at room temperature (25±5° C.), to allow deposition/precipitation of the SDS at reduced temperatures, for a time period of 3 hours. Following processing with the Second Processing Solution, ultrapure sterile water was circulated through the tissue and processing vessel such that the available volume of washing solution approximated a 1000-fold dilution of the SDS present in the Second Processing Solution with a flow rate of 50 ml/minute for 1.5 hours. Following washing in this final processing step, the vein was removed from the processing vessel and transferred into storage solution of 0.001% chlorine dioxide in sterile ultrapure water and packaged in a volume of this solution sufficient to cover the tissue.
EXAMPLE 8
Internal mammary artery tissues (two) from an acceptable human donor were carefully dissected under sterile conditions to remove all visible fat deposits and side vessels tied off using nonresorbable suture materials such that the ties did not occur in close proximity to the long run of the vessel. Sutures can restrict the decellularization process and the tissues under the sutures will be removed following decellularization. For short artery grafts (11 and 8 cm) (FIG. 1 ), one end of each artery were cannulated onto the ribbed attachment of the inlet port(s) and single sutures used to secure each arteries. At this point, the arteries were removed from the dissecting solution (ultrapure water containing 50 mM Tris-HCl (pH 7.2), 5 mM EDTA, and antibiotic solution for cardiovascular tissue procurement and transport) and transferred to the processing vessel(s) which had been temporarily inverted. Prior to closing the processing vessel, a portion of the First Processing Solution was gently added to the processing vessel and the inlet port, with attached artery, was then secured. At this point, the processing vessel was turned such that the inlet port was down and the outlet port was up and the vessel attached to its support racking system via clamps, respectively. Sterile disposable tubing was attached to the inlet port and to pump tubing in a peristaltic pump. Further, sterile disposable tubing was attached to the inflow side of the peristaltic pump and to the solution reservoir which contained all remaining first processing solution. Total processing solution volume approximated 150 ml. Finally, sterile disposable tubing was attached between the top (outlet) port of the processing vessel and the solution reservoir. Sterile, in-line, filters were added at appropriate positions in the fluid flow to safeguard sterility during processing. First Processing Solution was pumped into, through and out of the processing vessel such that flow of fluids through the luminal part of the artery tubule passed into the processing vessel to affect constant solution change in the processing vessel and out through the outlet port to a solution reservoir. By processing the artery in an inverted state, air which had been “trapped” in the luminal space of the vein was induced to exit facilitating equal access of the processing solutions to the vein tissue being processed. Processing of the artery tissue with the First Processing Solution was performed at temperatures approximating 25±5° C. for 16 hours using a flow rate of the First Processing Solution of 50 mls/hour. The First Processing Solution consisted of 50 mM Tris-HCl (pH 7.2), 5 mM MgCl 2 , 1% (w:v) Allowash Solution (as described in U.S. Pat. No. 5,556,379), and endonuclease (Benzonase, a registered product of EM Industries, Inc.) (41.8 Units/ml). Following processing with the First Processing Solution, the First Processing Solution was replaced with sterile ultrapure water amended with 0.5 M CaCl 2 (250 mls at a pump rate of 60 mls/minute) which was then replaced with an alkaline hypotonic solution containing about 0.001% by weight sodium dodecylsulfate (SDS) in ultrapure water buffered with 50 mM Tris-HCl (pH 8) (Second Processing Solution). Under this processing procedure, only sufficient ultrapure salt solution needed to be circulated through the processing vessel to affect one volume change of solution in the processing vessel. Under the processing with Second Processing Solution, this second solution was circulated (flow rate of 30 mls/min.) through the tissue at room temperature (25±5° C.), to allow precipitation of the SDS at reduced temperatures, for a time period of 3 hours. Following processing with the Second Processing Solution, ultrapure sterile water was circulated through the tissue and processing vessel such that the available volume of washing solution approximated a 1000-fold dilution of the SDS present in the Second Processing Solution with a flow rate of 50 ml/min. for 1.5 hours. Following washing in this final processing step, the artery was removed from the processing vessel and transferred into storage solution of 70% (v:v) pharmaceutical grade isopropanol in sterile ultrapure water and packaged in a volume of this solution sufficient to cover the tissue.
EXAMPLE 9
Aortic and pulmonary tissues (one each) from a heart of an acceptable human donor were carefully dissected under sterile conditions to remove all visible fat deposits and cardiac muscle tissue (leaving only a small but visible band of cardiac muscle tissue around the proximal end of the conduit. At this point, the valves were removed from the dissecting solution (ultrapure water and antibiotic solution for cardiovascular tissue procurement and transport) and transferred to the deformable (plastic) processing vessel(s). Prior to closing the processing vessel, a portion of the First Processing Solution was gently added to the processing vessel and the side access port closed using the clamping mechanism illustrated in FIG. 2 . The proximal end of the heart valve(s) was placed towards the inlet port and the distal end(s) of the valve was placed towards the outlet port. At this point, the processing vessel was placed such that the inlet port was down and the outlet port was up and the vessel attached to its support racking system via clamps. Sterile disposable tubing was attached to the inlet port and to pump tubing in a peristaltic pump. Further, sterile disposable tubing was attached to the inflow side of the peristaltic pump and to the solution reservoir which contained all remaining first processing solution. Total processing solution volume approximated 350 ml. Finally, sterile disposable tubing was attached between the top (outlet) port of the processing vessel and the solution reservoir. Sterile, in-line, filters were added at appropriate positions in the fluid flow to safeguard sterility during processing. First Processing Solution was pumped into, through and out of the processing vessel such that flow of fluids through the luminal part of the heart valve tubule passed into the processing vessel to affect constant solution change in the processing vessel and out through the outlet port to a solution reservoir. By processing the heart valve in an noninverted state, air which had been “trapped” in the luminal spaces behind the leaflets of the heart valve was induced to exit facilitating equal access of the processing solutions to the heart valve tissue being processed. Processing of the valve and conduit tissue with the First Processing Solution was performed at temperatures approximating 25±5° C. for 16 hours using a flow rate of the First Processing Solution of 50 mls/minute. The First Processing Solution consisted of 50 mM Tris-HCl (pH 8), 2 MM MgCl 2 , 1% (w:v) Allowash Solution (as described in U.S. Pat. No. 5,556,379), and endonuclease (Benzonase, a registered product of EM Industries, Inc.) (83 Units/ml). Following processing with the First Processing Solution, the First Processing Solution was replaced with sterile ultrapure water (350 mls at a pump rate of 50 mls/min. being recirculated over a period of 3 hours) which was then replaced with an alkaline hypertonic solution containing about 0.24% by weight sodium dodecylsulfate (SDS) in ultrapure water buffered with 50 mM Tris-HCl (pH 7.2) containing 0.5 M sodium chloride (Second Processing Solution). This specific formulation of SDS and sodium chloride is balanced so as not to precipitate the SDS, the SDS concentration is minimized to lessen extension of the tissue dimensions, the salt concentration is maximized so as to facilitate limited contraction of the tissue dimensions—yet not be so concentrated as to precipitate the anionic detergent, and the whole processing solution facilitates decellularization and treatment of the tissue yet promotes coaptation of the valve leaflets post decellularization. Second Processing Solution was replaced with a hypertonic solution of 0.005 M calcium hydroxide. Under this processing procedure, only sufficient ultrapure water salt solution needed to be circulated through the processing vessel to affect one volume change of solution in the processing vessel. Under the processing with Second Processing Solution, this second solution was circulated (flow rate of 30 mls/minute) through the tissue at room temperature (25±5° C.), to allow precipitation of the SDS at reduced temperatures, for a time period of 5 hours. Following processing with the Second Processing Solution, ultrapure sterile water containing calcium ion was circulated through the tissue and processing vessel such that the available volume of washing/treatment solution approximated a 1000-fold dilution of the SDS present in the Second Processing Solution with a flow rate of 50 ml/min. for 1.5 hours. Following washing in this final processing step, the heart valve(s) was (were) removed from the processing vessel and transferred into storage solution of 0.05% chlorine dioxide in sterile ultrapure water and packaged in a volume of this solution sufficient to cover the tissue.
While the invention has been described in connection with specific embodiments thereof, it will be understood that it is capable of further modifications and this application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the invention and including such departures from the present disclosure as come hypotonic buffered within known or customary practice within the art to which the invention pertains and as may be applied to the essential features hereinbefore set forth as follows in the scope of the appended claims. Any references including patents cited herein are incorporated herein in their entirety. | The invention provides methodologies and apparatus for producing acellular soft-tissue implants, both in small quantities and in commercializable quantities. Such soft-tissue implants include vascular graft substitutes. An acellular graft is produced by subjecting the tissue sample to an induced pressure mediated flow of an extracting solution, followed by inducing a pressure mediated flow of a treating solution, then washing the treated tissue to produce the acellular graft. The acellular grafts produced are uniform and non-immunogenic. The inventive method allows for the production of multiple decellularized soft tissue implants, where processing time is significantly less than prior art processes and the number of implants produced per day is increased over prior art processes. In clinical use, the decellularized grafts produced exhibit significantly improved in long-term durability and function. | 0 |
RELATED APPLICATIONS
[0001] The present application claims priority under 35 U.S.C. §119 of U.S. Application Ser. No. 61/151,393 filed Feb. 10, 2009.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT
[0002] The present invention was partially made with Government support under grant R44HL066830 awarded by the US National Heart Lung and Blood Institute, National Institutes of Health. The Government has certain rights in the invention.
FIELD OF THE INVENTION
[0003] The present invention relates to methods and apparatus for high pressure fluid flow control. In more specific embodiments, the present invention relates to an improved, propellant-driven medical inhaler device for producing respirable aerosols of biologically-active substances, and to methods of using such devices. In further embodiments, the invention relates to electronically-controlled high pressure fluid flow valves and to devices and methods employing such valves, for example, to improve the performance of aerosol devices for aerosolized drug inhalation.
BACKGROUND OF THE INVENTION
[0004] Control of low flow rates of high pressure fluids is important in many fields including, but not limited to, supercritical fluid extraction, supercritical fluid chromatography, critical point drying, high pressure small parts cleaning, petrochemical processing, and biofuels production. Accordingly, the device in the present invention can be used advantageously in these fields to improve flow control of the high pressure fluids involved.
[0005] A very common method of administering biologically-active substances, such as asthma drugs, to the lungs involves the generation of respirable aerosols from pressurized metered dose inhalers (pMDIs). The typical pMDI comprises a small canister containing a suspension of drug particles or solution of dissolved drug in a compressed liquid propellant such as, formerly, CFC-11 and/or CFC-12, or, currently, HFA-134a. A mechanical means is used to fill a metering chamber with the pressurized suspension, and the chamber is allowed to decompress and spray out into an inhalation zone, flash evaporating the propellant and releasing airborne drug particles. Aerosols are generated by both the gas expansion energy and solvent evaporation.
[0006] Hand-held pressurized metered-dose inhalers (pMDIs) are commonly used to deliver bronchodilators and anti-inflammatory drugs to the lungs to treat asthma and chronic obstructive pulmonary diseases. Effective and safe aerosol delivery of pharmaceuticals to the lungs is limited by the solvents and propellants that can be used in inhalers. Until recently chlorofluorocarbon (CFC) propellants 11 (trichlorofluoromethane) and 12 (dichlorodifluoromethane) were the most commonly used propellant gases, but their use has been largely phased out in accordance with the Montreal Protocol due to the ozone-depleting properties of CFC propellants. Alternative propellants for pMDIs have become a necessary pursuit of the pharmaceutical industry. The Montreal Protocol is an international treaty that was drafted in 1987 to phase out the commercial production of all ozone-depleting CFCs. The US FDA, EPA, and DOE each have programs to eliminate production and use of all CFCs. The US FDA will not accept new drug applications for any MDI formulations that use CFCs as propellants. The EPA is expecting the pharmaceutical industry to comply with the Montreal Protocol as soon as proven alternative aerosol delivery techniques are developed for most pharmaceuticals.
[0007] Valves used to control high pressure fluid flow at low flow rates are problematic. U.S. Pat. No. 6,032,836 teaches that a metering chamber system can be used to deliver aliquots of high pressure fluid propellants such as liquid carbon dioxide to a low pressure inhalation zone, using a chamfered chamber region with a typical volume of 50 μL around a push pin mounted transversely to a high pressure inlet and low pressure outlet, for manual movement of the chamber from filling to discharging positions. Notably, the dose metering is based on the common approach of physically moving a metering chamber from a filling to discharging position, so it shares the drawbacks of this approach with standard, lower-pressure pMDIs charged with CFC or HFA propellants.
[0008] Unfortunately, pMDIs based on prior art have several problems and drawbacks. Notably, metered dose inhalers dispense aliquots of drug-containing propellant suspensions by capturing a small, fixed volume in a movable chamber under pressure and then opening this fixed volume chamber to room atmosphere so that the propellant can expand and drive the drug particles to become airborne. Such an approach has the problem that the movable chamber used to capture the aliquot is of fixed volume, so that the delivered drug amount is subject to change as the density of the propellant changes due to temperature changes, number of doses already administered from the canister, or other means. Plus, even under ideal temperature storage conditions, the dose size is fixed, and cannot be adjusted.
SUMMARY OF THE INVENTION
[0009] The present invention is provided to overcome one or more disadvantages of the prior art.
[0010] In one embodiment, the invention is directed to a fluid flow control valve which comprises (a) a high pressure region adapted to contain a fluid at its supercritical or nearcritical temperature and pressure conditions and connected via an orifice to a low pressure region, (b) a seat adjacent the orifice, (c) a sealing element positionable against the seat to form a seal between the high pressure region and the low pressure region, and (d) an electrically and/or electronically controlled actuator operable to move the sealing element against and/or away from the seat to allow control of fluid flow from the high pressure region to the low pressure region. In a specific embodiment, the high pressure region contains a fluid at its supercritical or nearcritical temperature and pressure conditions and the fluid comprises carbon dioxide, nitrogen, ethanol, difluoromethane, 1,1,1,2-tetrafluoroethane, or 1,1,1,2,3,3,3-heptafluoropropane, or a mixture of two or more thereof. The valve may be used, for example, to provide very low flow rates, for example, for supercritical fluid chromatography, supercritical fluid extraction, critical point drying, supercritical fluid cleaning, and supercritical fluid separation methods. In another embodiment, the valve is suitable for use in methods of delivering a biologically active substance to a patient in need thereof.
[0011] In another embodiment, the invention is directed to fluid flow control valve for aerosol delivery of biologically active materials for inhalation administration. The valve comprises (a) a high pressure region containing a pressurizable fluid and connected via an orifice to a low pressure region from which inhalation is conducted, (b) one or more biologically active substances dissolved and/or suspended in the pressurizable fluid, (c) a seat adjacent the orifice, (d) a sealing element positionable against the seat to form a seal between the high pressure region and the low pressure region, (e) an electrically and/or electronically controlled actuator operable to move the sealing element against and/or away from the seat to allow control of fluid flow from the high pressure region to the low pressure region, and (f) one or more electronic components operable to perform one or more functions of metered dose inhalation.
[0012] Additional features and embodiments of the invention will be apparent form the following detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] Specific embodiments and features of the invention are depicted in the figures, using reference numerals as indicated, and these embodiments and features are illustrative and non-limiting of the invention described herein, wherein:
[0014] FIG. 1 is a schematic diagram depicting a cross section of the valve assembly (the valve) of the invention in a first embodiment.
[0015] FIG. 2 is a schematic diagram depicting a cross section of the valve of the invention in another embodiment.
[0016] FIG. 3 is a schematic diagram depicting a cross section of the valve of the invention in another embodiment.
[0017] FIG. 4 is a schematic diagram depicting a cross section of the valve of the invention in another embodiment.
[0018] FIG. 5 is a schematic diagram depicting a cross section of the valve of the invention in another embodiment.
[0019] FIG. 6 is a schematic diagram depicting a cross section of the valve of the invention in another embodiment.
[0020] FIG. 7 is a schematic diagram depicting a cross section of the valve of the invention in another embodiment.
[0021] FIG. 8 is a schematic diagram a cross section of depicting the valve of the invention in another embodiment.
[0022] FIG. 9 is a schematic diagram depicting a cross section of the valve of the invention in another embodiment.
[0023] FIG. 10A is a schematic diagram depicting a cross section of the valve of the invention in another embodiment.
[0024] FIG. 10B shows an enlarged view of the indicated portion of FIG. 10A .
[0025] FIG. 11A shows a perspective view depicting the valve of the invention in another embodiment.
[0026] FIG. 11B is a schematic diagram depicting a cross section of the valve of FIG. 11A , taken along the plane shown in FIG. 11A .
[0027] FIG. 12A shows a perspective view depicting the valve of the invention in another embodiment.
[0028] FIG. 12B is a schematic diagram depicting a cross section of the valve of FIG. 12A , taken along the plane shown in FIG. 12A .
[0029] FIG. 12C shows an enlarged view of the indicated portion of FIG. 12B .
[0030] FIG. 13 is a schematic diagram depicting the valve of the invention in another embodiment.
[0031] FIG. 14 is a schematic diagram depicting the valve of the invention in another embodiment.
[0032] FIG. 15A is a schematic diagram depicting a cross section of the valve of the invention in another embodiment.
[0033] FIG. 15B shows an enlarged view of the indicated portion of FIG. 15A .
[0034] FIG. 16 is a schematic diagram depicting the valve of the invention in another embodiment.
[0035] FIG. 17 is a schematic diagram depicting the valve of the invention in another embodiment.
[0036] The drawings will be more fully understood in view of the detailed description.
DETAILED DESCRIPTION
[0037] The invention provides various advantages in certain embodiments. For example, it is an advantage in certain embodiments of the invention to provide an electronically-controlled valve, which allows for improved control and easy record-keeping functions compared to mechanical valves currently used in high pressure fluid flow control valves in general and pressurized metered dose inhalers in particular.
[0038] It is a further advantage in certain embodiments of the invention that said electronically-controlled high pressure fluid control valve overcomes the problems of low flow rate control commonly associated with other valves currently used to control the flow of high pressure fluids, allowing precise metering of the flow of high pressure fluids instead of simply being in a discrete on or off state. This advantage can be realized in the present invention by variable valve opening, by controlled duration of valve opening, by controlled duration and frequency of rapid valve open/close cycling, or by a combination of such mechanisms.
[0039] It is a further advantage in certain embodiments of the invention that said electronically-controlled valve can be designed, tuned, and/or programmed to improve dose reproducibility relative to mechanically-controlled valves by compensating for temperature, doses already delivered, amount of propellant remaining in the canister, storage conditions between discharges, and other variables.
[0040] It is a further advantage in certain embodiments of the invention that said electronically-controlled valve can be programmed to allow adjustment of the delivered dose size based on the needs of the individual patient using it.
[0041] It is a further advantage in certain embodiments of the invention that said electronically-controlled valve can be programmed to prevent medication misuse and/or overdose by limiting the number of doses, controlling the minimum time between doses, requiring patient identification prior to dose delivery, counting doses delivered and/or remaining, and other relevant parameters.
[0042] It is a further advantage in certain embodiments of the invention that said electronically-controlled valve utilizes an electronic control system which facilitates control of oscillation frequency, pulse width modulation, vibration timing and amplitude, and other means to control the timing and repetition of valve opening and closure.
[0043] It is a further advantage in certain embodiments of the invention to provide a valve system which overcomes the problems of solids formation at the low pressure side of valves used to control flow of high pressure carbon dioxide solutions.
[0044] From the detailed description and diagrams herein, a number of additional advantages in certain embodiments of the present invention are evident: 1. The electronic control system can include an LCD counter display which can provide a 3 digit resolution counter for showing doses taken and doses remaining in the device. The electronic control system may work easier for dose counting than mechanical or other valve systems. 2. The electronically-controlled inhaler can notify audibly and/or visually when it is close to or at the last dose. 3. Electronic temperature compensation allows the electronically-controlled pMDI to be used at high and low temperatures, allowing its use in a broader temperature range than mechanical or other uncompensated pMDI systems. 4. Electronic counter can also be used for the electronically-controlled pMDI to self-compensate for pressure drop when the device is gradually emptied. 5. The electronically-controlled valve may not require a wasted priming puff.
[0045] Embodiments of the invention are depicted in FIGS. 1-17 . To facilitate clarity in the description of crucial aspects of the invention, well-known components, well-known electrical circuits, well-known fittings, and well-known procedures are not described in detail. The invention can, of course, take the form of additional embodiments, so the embodiments that are described are intended to describe and teach the invention without limiting the specific details of the invention.
[0046] The following reference numerals are used to designate the respective elements:
DRAWINGS
Reference Numerals
[0000]
1 high pressure region
2 pressurized fluid solution and/or suspension
3 low pressure region
4 seat
5 valve body
6 actuator
7 movement of fluid
8 plume of expanded fluid and aerosol particles
11 valve for pressure relief or filling or both
12 electrical connector
20 piezoelectric actuator
21 high pressure vessel
22 electrically-conductive standoff
23 electrically-conductive tether
24 electrically-conductive spring
25 electrically-insulating fastener
26 rigid beam
27 adjustable pushing pin
28 lever arm
29 Fulcrum
30 pushing means
31 Insulator
32 mounting arms
33 pushing pin
34 support pin
35 rigid mounting arm
36 pushing means
37 Post
38 support for electromagnetic windings
39 permanent ring magnet
40 permeable flux ring
41 permeable back material
42 nonconductive standoff
43 Fastener
44 U-shaped bimetal strip
45 insulating fastener
46 Wire
47 pressure seal insulator
50 piezoelectric disk
51 metal disk
52 adjustable mounting stud
53 mounting nut
54 exit tube
55 sealing film
56 threaded hole
57 leaf spring
58 rigid mounting arm
60 elastic beam
61 attachment point
62 mounting cylinder
63 electromagnetic wire windings
64 pushing means
65 magnetically permeable movable member
66 magnetically permeable housing
67 pushing means
68 bimetal strip
70 electric wire
71 Insulator
72 electric wire
[0106] In its simplest form, as depicted in FIG. 1 and FIG. 2 , the invented valve assembly comprises a high pressure region 1 containing a pressurized fluid solution and/or suspension 2 , a low pressure region 3 , a seat 4 , a valve body 5 which, when in the closed position, creates a seal between the high and low pressure regions, and an actuator 6 which, when engaged to open the valve, displaces the valve body and allows the movement 7 of said fluid from the high pressure region to the low pressure region, creating a plume of expanded fluid and aerosol particles 8 . The seat and valve body can be positioned within the low pressure region ( FIG. 1 ) or, alternatively, within the high pressure region ( FIG. 2 ). The actuator is preferably an electronically-controlled means to push or pull the valve body to displace it from the seat. Within the present description, electronically controlled is defined to mean that passing electric current through a component of the actuator causes the actuator to move and overcome a bias to push or pull the seal from the seat. Discontinuing the flow of current through the actuator component discontinues the force causing movement and the bias returns the seal to the seat. One of ordinary skill in the art will appreciate that the flow of current may be controlled in various respects, including rate and duration, to selectively dispense aerosol particles. In specific embodiments as discussed in detail below, the movement of the actuator can be achieved through contraction or expansion of a component or by generation of an electromagnetic force. Other embodiments resulting in movement of the actuator within the scope of the present invention will be apparent to one of ordinary skill in the art in view of the present disclosure.
[0107] FIG. 1 is a diagram depicting the valve assembly (valve) of the invention in a first embodiment. A high pressure region 1 containing a high pressure fluid and dissolved or suspended drug substance 2 , and a low pressure region 3 are separated by a valve body 5 positioned inside the high pressure region such that when the valve body is in the closed position it creates a seal against a seat 4 between the high and low pressure regions, and which can be opened by an electronically-driven actuator 6 and allow release at 7 of fluid and drug from the high pressure region to the low pressure region, and expansion of the fluid which forms an aerosol plume 8 . Notably, other pressurized fluids can be utilized instead of carbon dioxide in this invention, with those skilled in the art recognizing that the supercritical fluid solvent can be selected from a list of pressurized solvents including, but not limited to, carbon dioxide, HFC-134a (1,1,1,2-tetrafluoroethane), and HFC-227 (1,1,1,2,3,3,3-heptafluoropropane, aka HFC-227ea). Advantages to the general form of this embodiment with the valve body 5 in the high pressure region 1 include the use of such design as a fill valve to force high pressure fluids into the high pressure region.
[0108] FIG. 2 is a diagram depicting another embodiment of the valve assembly of the invention. A high pressure region 1 containing a high pressure fluid and dissolved or suspended drug substance 2 , and a low pressure region 3 are separated by a valve body 5 positioned in the low pressure region such that when the valve body is in the closed position it creates a seal against a seat 4 between the high and low pressure regions, and which can be opened by an electronically-driven actuator 6 and allow release at 7 of fluid and drug from the high pressure region to the low pressure region, and expansion of the fluid which forms an aerosol plume 8 . Notably, other pressurized fluids can be utilized instead of carbon dioxide in this invention, with those skilled in the art recognizing that the supercritical fluid solvent can be selected from a list of pressurized solvents including, but not limited to, carbon dioxide, HFC-134a (1,1,1,2-tetrafluoroethane), and HFC-227 (1,1,1,2,3,3,3-heptafluoropropane, aka HFC-227ea). Notably, this arrangement with the valve body 5 positioned in the low pressure region allows it to act as a pressure relief valve in case the pressure in the high pressure region 1 gets too high, because the actuator 6 can be adjusted so that it presses the valve body 5 against the set 4 with a low enough force that overpressure in the high pressure region 1 can force it open, making it the primary pathway for relief of pressure from the high pressure region 1 . Advantages to the general form of this embodiment with the valve body 5 in the low pressure region 1 include the aforementioned pressure relief valve usage and simplified electrical connectivity to valve components.
[0109] Hand held inhaler devices incorporating the present invention were built and tested for aerosol size distribution using pharmaceuticals that are commonly used for asthma treatment. In specific embodiments, pressurized carbon dioxide (CO 2 ) was employed, and several advantages to the use of pressurized CO 2 were established:
[0110] 1. CO 2 is a suitable MDI propellant replacement because it has zero ozone depletion potential and a global warming potential less than 0.1% of the new HFA propellants
[0111] 2. CO 2 MDI propellant generates aerosols in a narrow size range that are most likely to reach the lungs.
[0112] 3. CO 2 is the only propellant that can stimulate deep breathing and increase the deposition of aerosols in the lungs for more efficient delivery of pharmaceuticals.
[0113] 4. Many of the surfactants and solvent modifiers approved for inhaler formulations are very soluble in carbon dioxide.
[0114] 5. Many of the pharmaceuticals that are currently used to treat asthma are soluble in carbon dioxide.
[0115] 6. The toxicology of carbon dioxide is well understood because it has been in our lungs throughout human existence and has been used extensively in anesthesiology (especially Europe)
[0116] 7. The low reactivity of carbon dioxide is well known because it has been extensively studied for pharmaceutical extraction and processing.
[0117] 8. The high energy expansion of carbon dioxide can generate respirable aerosols of viscous liquids and sticky solids that cannot be collected for dry powder inhalers.
[0118] 9. Carbon dioxide has been used to generate pharmaceutical aerosols that have not been generated by any other method.
[0119] 10. Carbon dioxide MDIs can be used for both local lung therapy and systemic drug delivery.
[0120] FIGS. 3-17 disclose additional embodiments of the invention.
[0121] In another embodiment, depicted in FIG. 3 , the actuator 6 comprises a shape memory alloy (SMA) wire 6 mounted within the high pressure region 1 by attachment to an electrically-conductive standoff 22 and connected to an electrically-conductive valve body 5 which in this embodiment is pin-shaped and seated against an electrically-insulating seat 4 and pulled down into sealing position in the low pressure region 3 by an electrically-conductive tether 23 which is partially coiled into a spring form 24 , electrically-isolated at the low pressure end by insulator 25 , so that when electrical current is passed through the shape memory alloy (SMA) wire actuator 6 , it contracts and breaks the seal between the valve body 5 in the form of a pin and the seat 4 so that the high pressure fluid 2 contained within the vessel 21 is allowed to be released into the low pressure region 3 . The SMA wire material can include, but is not limited to, a nickel titanium alloy known as Nitinol in which heat treatment while under stress to stretch the material results in an elongated shape which attempts to revert back to its original shape when heated to a temperature above its transformation temperature, as accomplished by resistive heating in the present example. Also depicted in this embodiment is a valve 11 for filling, pressure relief, or both, adding advantages of convenient filling and pressurization and enhanced safety.
[0122] In another embodiment, depicted in FIG. 4 , the actuator 6 comprises a shape memory alloy (SMA) wire 6 mounted within the high pressure region 1 by attachment to an electrically-conductive standoff 22 and connected to an electrically-conductive valve body 5 which in this embodiment is ball-shaped and seated against an electrically-insulating seat 4 and pulled down into sealing position in the low pressure region 3 by an electrically-conductive tether 23 which is partially coiled into a spring form 24 , electrically-isolated at the low pressure end by insulator 25 , so that when electrical current is passed through the SMA wire actuator 6 , it contracts and breaks the seal between the valve body 5 in the form of a ball and the seat 4 so that the high pressure fluid 2 contained within the vessel 21 is allowed to be released into the low pressure region 3 .
[0123] In another embodiment, depicted in FIG. 5 , the actuator 6 comprises a shape memory alloy (SMA) wire 6 mounted within the high pressure region 1 by attachment to an electrically-conductive standoff 22 and connected to an electrically-conductive valve body 5 which, in this embodiment, is pin-shaped and seated against an electrically-insulating seat 4 , so that when electrical current is passed through the electrical connector 12 , the pin 5 , the SMA wire actuator 6 , the electrically conductive standoff 22 , and the electrically conductive pressure vessel body 21 , the SMA wire contracts and breaks the seal between the valve body 5 and the seat 4 so that the high pressure fluid 2 contained within the vessel 21 is allowed to be released into the low pressure region 3 . The internal pressure in the high pressure region 1 holds the pin in a position which facilitates sealing and resealing after opening.
[0124] In another embodiment, depicted in FIG. 6 , the actuator comprises a pushing means such as a piezoelectric actuator 20 pushing across an intervening insulator 71 to a lever arm 28 mounted to a fulcrum 29 . The lever arm includes at the opposite end an adjustable push pin 27 pressing on a sealing element 5 , which in this example is ball-shaped, to seat it against the sealing seat 4 when in the closed position and thereby contain the fluid and dissolved or suspended drug 2 in the high pressure region 1 contained within a high pressure vessel 21 . In this embodiment, when the piezoelectric actuator 20 is induced to contract by passing electric current through it via electric wire 70 and either through a second electric wire at its other end where it contacts the pressure vessel 21 or through electrical contact of the piezoelectric actuator 20 to the pressure vessel 21 and grounding of said vessel at another location, said contraction allows the sealing element 5 to unseat from the sealing seat 4 , allowing high pressure fluid and dissolved or suspended drug 2 to be released from the high pressure vessel 21 into the low pressure region 3 .
[0125] In another embodiment, depicted in FIG. 7 , the actuator 6 comprises a shape memory alloy (SMA) wire 6 mounted in the low pressure region 3 by attachment with an intervening insulator 31 to a lever arm 28 pivoting on a fulcrum 29 with the opposite end pressed with a spring or other pushing means 30 so that the adjustable pin 27 in said lever arm presses a sealing means 5 , which in this embodiment is ball-shaped, to seat it against the sealing seat 4 when in the closed position and thereby contain the fluid and dissolved or suspended drug 2 in the high pressure region 1 contained within a high pressure vessel 21 . The arm 28 can be made thin enough to apply spring force itself to the pin 27 and sealing means 5 . In this embodiment, when electrical current is passed through the SMA wire actuator 6 , it contracts and pulls the lever arm 28 hard enough to overcome the pushing means 30 , such as a spring, and unseat the sealing means 5 from the sealing seat 4 , allowing high pressure fluid and dissolved or suspended drug 2 to be released from the high pressure vessel 21 into the low pressure region 3 .
[0126] In another embodiment, depicted in FIG. 8 , the actuator 6 comprises a shape memory alloy (SMA) wire 6 mounted in the low pressure region 3 by attachment of each end of 6 using insulators 31 to mounting arms 32 out from the sealing seat 4 and with said SMA wire 6 connected to the sealing means 5 which in this embodiment is ball-shaped and seated against a seat 4 when in the closed position. Said sealing means 5 is pressed against said seat 4 by a pushing pin 33 that has adjustable position by its connection to a support pin 34 mounted to a rigid mounting arm 35 and including a pushing means 36 , such as a spring, so that when electrical current is passed through the SMA actuator 6 , it pulls the sealing means 5 away from the sealing seat to break the seal between the sealing means ball 5 and the seat 4 so that the high pressure fluid and dissolved or suspended drug 2 contained within the vessel 21 is allowed to be released into the low pressure region 3 . This embodiment has the advantage that the cooling effect of the fluid expansion from the high pressure region 1 to the low pressure region 3 cools the SMA wire actuator 6 , reducing the response time and improving control.
[0127] In another embodiment, depicted in FIG. 9 , the actuator comprises a magnetically permeable movable member 65 with a push post 37 exerting force against a valve body 5 , which is ball-shaped in this embodiment, to press it against a seat 4 when in the closed position to create a seal and capture the high pressure fluid and dissolved or suspended drug 2 within the high pressure region 1 contained within the pressure vessel 21 . The moveable member 65 and post 37 are pressed into position by a pushing means 64 , such as a spring, with enough force to seat the valve body 5 against the seat 4 , and when electrical current is directed through the electromagnetic wire windings 63 wound around a magnetically permeable housing 66 a magnetic field is generated which attracts the moveable member 65 towards the pushing means 64 with enough force and/or momentum to open the seal between the valve body ball 5 and the seat 4 so that the high pressure fluid and dissolved or suspended drug 2 contained within the vessel 21 is allowed to be released into the low pressure region 3 .
[0128] In another embodiment, depicted in FIG. 10 , the actuator comprises a support for electromagnetic windings 38 , such as in a voice coil, integrally bonded to electromagnetic wire windings 63 and with a push post 37 exerting force against a valve body 5 , which is ball-shaped in this embodiment, to press it against a seat 4 when in the closed position to create a seal and capture the high pressure fluid and dissolved or suspended drug 2 within the high pressure region 1 contained within the pressure vessel 21 . The support for electromagnetic windings 38 and post 37 are pressed into position by a pushing means 67 , such as a spring, with enough force and/or momentum to seat the valve body 5 against the seat 4 , and when electrical current is directed through the electromagnetic wire windings 63 bound to the voice coil housing, a magnetic field is generated which attracts the support for electromagnetic windings 38 towards the permanent ring magnet 39 using magnetic flux traveling through a permeable flux ring 40 and permeable back material 41 , so that the support for electromagnetic windings 38 and post 37 are pulled towards the pushing means 67 with enough force and/or momentum to open the seal between the valve body 5 and the seat 4 so that the high pressure fluid and dissolved or suspended drug 2 contained within the vessel 21 is allowed to be released into the low pressure region 3 .
[0129] In another embodiment, depicted in FIG. 11 , the actuator comprises a U-shaped bimetal strip 44 mounted in the low pressure region 3 by attachment of each end of 44 using nonconductive standoffs 42 and fasteners 43 so that the middle of the U-shape of the bimetal strip presses against a sealing means 5 which in this embodiment is ball-shaped and seats it against a seat 4 when in the closed position. Said U-shaped bimetal strip 44 is preloaded to force the sealing means 5 against the seat 4 , and when electrical current is passed through the U-shaped bimetal strip 44 , it bends away from the sealing means 5 and the sealing seat 4 , breaking the seal between the sealing means 5 and the seat 4 so that the high pressure fluid and dissolved or suspended drug 2 contained in the high pressure region 1 within the vessel 21 is allowed to be released into the low pressure region 3 . The amount of flow allow to be released from the high pressure region 1 is controlled by the intensity and duration of the electrical pulse applied through the bimetal strip. This embodiment has the advantage that the cooling effect of the fluid expansion from the high pressure region 1 to the low pressure region 3 cools the bimetal strip 44 , reducing the response time and improving control. In this embodiment is also depicted a fill or pressure relief valve 11 .
[0130] In another embodiment, depicted in FIG. 12 , the actuator comprises a bimetal strip 68 mounted in the low pressure region 3 in a spring-like fashion by rolling over each end of 68 and attaching each end of 68 using nonconductive standoffs 42 and fasteners 43 so that the middle of said bimetal strip presses against a sealing means 5 which in this embodiment is ball-shaped and seats said sealing means 5 against a sealing seat 4 when in the closed position. Said bimetal strip 68 is preloaded to force the sealing means 5 against the seat 4 , and when electrical current is passed through the bimetal strip 68 , it bends away from the sealing means 5 and the sealing seat 4 , breaking the seal between the sealing means 5 and the seat 4 so that the high pressure fluid and dissolved or suspended drug 2 contained in the high pressure region 1 within the vessel 21 is allowed to be released into the low pressure region 3 . In typical use, the center of the bimetal strip 68 would be narrower than the ends so that the voltage drop is higher at the site of contact with the sealing means 5 . In this way, when current is passed through the bimetal strip 68 , using for example electric wire 72 to connect to each end of said bimetal strip, most of the heating and deflection occurs in the narrow region of the bimetal strip 68 , and cooling of the bimetal strip 68 occurs due to the expanding fluid flow, which serves to improve valve control. In this embodiment is also depicted a valve 11 used for filling and/or pressure relief purposes.
[0131] In another embodiment, depicted in FIG. 13 , the actuator 6 comprises a shape memory alloy (SMA) wire 6 mounted within the high pressure region 1 by attachment to an electrically-conductive standoff 22 , in this example a rigid metal tubular structure, and connected to an electrically-conductive valve body 5 , which in this embodiment is pin-shaped and seated against an electrically-insulating seat 4 , and pushed down into sealing position by pressure in the high pressure region 1 and pulled down into sealing position by an electrically-conductive tether 23 in the low pressure region 3 such that said tether 23 is attached using an electrically insulating fastener 25 to a leaf spring 57 attached to the pressure vessel 21 by means of a rigid mounting arm 58 , so that the valve body 5 is pulled into a sealing position by the leaf spring 57 when in the closed position but when electrical current is passed through the SMA wire actuator 6 , it contracts and breaks the seal between the valve body 5 and the seat 4 so that the high pressure fluid 2 contained within the vessel 21 is allowed to be released into the low pressure region 3 . Further, when no current is passed through the SMA wire 6 , the leaf spring 57 and the internal pressure in the high pressure region 1 within the pressure vessel 21 both facilitate reseating of the valve body 5 against the seat 4 , stopping the release of high pressure fluid and drug 2 from the pressure vessel 21 into the low pressure region 3 . This embodiment has the advantage that the heated SMA wire actuator 6 in the high pressure region 1 allows preheating of the high pressure fluid during actuation of the valve.
[0132] In another embodiment, depicted in FIG. 14 , the actuator 6 comprises a shape memory alloy (SMA) wire 6 with a bend in the middle mounted within the high pressure region 1 by passing each end of the SMA wire 6 through insulating fasteners 45 and attachment of fastener 45 to a standoff 22 and fastening of each end of the SMA wire 6 to the standoff by means of the insulating fasteners 45 . Said SMA wire 6 is connected at said bend in middle to a valve body 5 , which in this embodiment is pin-shaped and seated against a seat 4 and pushed down into sealing position by pressure in the high pressure region 1 when in the closed position. Each end of the SMA wire 6 is further connected to conductive wires 46 which pass through pressure seal insulators 47 facilitating the passage of electrical current from access to the wires 46 in the low pressure region 3 to actuate the SMA wire 6 so that it contracts and pulls the valve body 5 away from the seat 4 so that the seal is broken and the high pressure fluid and drug 2 contained in the high pressure region 1 within the vessel 21 is allowed to be released into the low pressure region 3 .
[0133] In another embodiment, depicted in FIG. 15 , the actuator comprises a piezoelectric disk 50 conductively and mechanically bonded to a metal disk 51 mounted to the pressure vessel 21 by means of a multiplicity of adjustable mounting studs 52 threaded into mounting nuts 53 and threaded holes 56 attached to the pressure vessel 21 . Location of said bonded piezoelectric disk 50 and metal disk 51 are adjusted so that a sealing film 55 bonded to the disk 51 surface opposite the piezoelectric disk 50 presses against an exit tube 54 attached to the pressure vessel 21 so that the inside of the tube 54 is contiguous with the high pressure region 1 containing the pressurized fluid and drug 2 and so that the contact between the sealing film 55 and the exit tube 54 create a seal and prevent the high pressure fluid and drug 2 from release into the low pressure region 3 when in the closed position. Further, application of DC bias voltage and/or oscillating voltage to the piezoelectric disk 50 induces it to move and break the seal between the sealing film 55 and the tube 54 allowing controlled release of high pressure fluid and drug 2 contained in the vessel 21 to pass through the tube 54 and out of the open end of the tube 54 into the low pressure region 3 .
[0134] In another embodiment, depicted in FIG. 16 , the actuator comprises a piezoelectric disk 50 conductively bonded to a metal disk 51 mounted to the pressure vessel 21 by means of a multiplicity of adjustable mounting studs 52 threaded into mounting nuts 53 and threaded holes 56 attached to the pressure vessel 21 . Location of said bonded piezoelectric disk 50 and metal disk 51 are adjusted so that the disk 51 surface opposite the piezoelectric disk 50 presses against a sealing means 5 , in this embodiment ball-shaped, seated at the end of an exit tube 54 which is attached to the pressure vessel 21 so that the inside of the tube 54 is contiguous with the high pressure region 1 containing the pressurized fluid and drug 2 . Further, said pressing of the sealing means 5 against the end of the exit tube 54 creates a seal and prevents the high pressure fluid and drug 2 from release into the low pressure region 3 when in the closed position. Further, application of DC bias voltage and/or oscillating voltage to the piezoelectric disk 50 induces it to move and break the seal between the sealing means 5 and the tube 54 allowing controlled release of high pressure fluid and drug 2 contained in the vessel 21 to pass through the tube 54 and out of the open end of the tube 54 into the low pressure region 3 .
[0135] In another embodiment, depicted in FIG. 17 , the actuator 6 comprises a shape memory alloy (SMA) wire 6 mounted in the low pressure region 3 by attachment of each end of 6 using insulating fasteners 45 to rigid mounting arms 58 . This embodiment further comprises an exit tube 54 which is attached to the pressure vessel 21 so that the inside of the tube 54 is contiguous with the high pressure region 1 containing the pressurized fluid and drug 2 , a mounting cylinder 62 holding a cutaway disk possessing an elastic beam 60 across its center, positioned so that said beam 60 presses against a valve body 5 , in this case ball-shaped, seated at the end of said exit tube 54 . Further, said pressing of the valve body 5 against the end of the exit tube 54 creates a seal and prevents the high pressure fluid and drug 2 from release into the low pressure region 3 when in the closed position. Further, the SMA wire 6 is attached to the middle of the elastic beam at the middle of the SMA wire 6 by means of an attachment point 61 on the elastic beam such that passage of electrical current through the SMA wire 6 induces it to contract and pull on the elastic beam 60 and break the seal between the valve body 5 and the tube 54 allowing controlled release of high pressure fluid and drug 2 contained in the vessel 21 to pass through the tube 54 and out of the open end of the tube 54 into the low pressure region 3 .
[0136] Skilled persons will appreciate that the present invention facilitates flow control of high pressure fluids and provides an electronically-controlled valve for use in an electronic metered dose inhaler with many advantages over existing devices.
[0137] The following examples illustrate certain embodiments of the invention.
Example 1
[0138] A valve according to FIG. 5 is constructed and mounted onto an aluminum canister pressure vessel with an internal volume of 12 mL, incorporating a shape memory alloy actuator wire conductively mounted to an electrically-conductive standoff inside the canister, and a gold-plated metal pin as the sealing element seated against an elastomeric seat. The canister is pressurized to about 900 psi with carbon dioxide, and metered releases of carbon dioxide gas are effected by application of sufficient current to the shape memory alloy wire to cause it to contract and pull the pin away from the seat. After each release of pressurized gas from the canister into room pressure, after stopping the application of DC current to the shape memory alloy wire actuator, the pin returns to the closed position against the seat and the flow stops. The process is repeated several times. Finally, after pressurizing the canister with 2.88 g of carbon dioxide and sealing the canister with the aforementioned gold pin against the elastomeric seat, the leak rate was measured. After 480 days, 97.8% of the originally-loaded carbon dioxide is still contained within the canister, indicating a low leak rate and a good valve seal.
Example 2
[0139] A valve according to FIG. 11 is constructed so that the metal ball sealing element, 1 mm diameter, is seated into the end of a 1.6 mm outer diameter stainless steel tube into which an internal beveled edge had been cut to facilitate seating of the ball against the tube. The ball is pressed into place with a U-shaped bimetal strip, preloaded with enough tension to hold the ball sealed against the tube when 2000 psi of pressure is applied inside the tube, and 2000 psi is maintained going into the tube with carbon dioxide. When current is passed through the bimetal strip, it bends away from the tube, sufficiently to allow the ball to move away from the tube and allow carbon dioxide to flow out of the tube into room pressure. It is determined that the flow rate is proportional to the amount of electrical current passed though the bimetal strip, and the valve is demonstrated to open and close through dozens of cycles of applying electrical current.
Example 3
[0140] A valve according to FIG. 15 is constructed using a 0.4 mm OD tube through which flow is controlled from a region of 900 psi carbon dioxide to room pressure. A thin layer of polyurethane, approximately 0.2 mm thick, is applied to the surface of a 20 mm diameter brass disk on the opposite side from piezoelectric ceramic material conductively attached to the disk, also known as a piezoelectric bender. The disk is mounted perpendicular to the tube with the urethane coating pressed against the end of the tube with sufficient force to seal the tube against flow of the 900 psi carbon dioxide into the room pressure region. Eighty volts DC are applied to the piezoelectric bender, along with 6 kHz oscillating voltage, which bends the disk away from the tube and allows carbon dioxide flow to exit the tube. This actuation is repeatedly tested for 2500 on/off cycles of 0.8 sec on and about 7 sec off, and the valve is found to repeatedly release metered pulses of carbon dioxide gas and then reseal at the end of the test.
Example 4
[0141] A valve according to FIG. 15 is constructed using a 0.4 mm OD tube through which flow is controlled from a region of approximately 80 psi of 1,1,1,2-tetrafluoroethane (HFC-134a) to room pressure. A thin layer of polyurethane, approximately 0.2 mm thick, is applied to the surface of a 20 mm diameter brass disk on the opposite side from piezoelectric ceramic material conductively attached to the disk, also known as a piezoelectric bender. The disk is mounted perpendicular to the tube with the urethane coating pressed against the end of the tube with sufficient force to seal the tube against flow of the 80 psi 1,1,1,2-tetrafluoroethane into the room pressure region. One hundred ten volts DC are applied to the piezoelectric bender, along with oscillating voltage, 8 kHz, 10 volts AC, which bends the disk away from the tube and allows 1,1,1,2-tetrafluoroethane flow to exit the tube. This actuation is repeatedly tested for 1000 on/off cycles of 0.8 sec on and about 7 sec off, and the valve is found to repeatedly release metered pulses of 1,1,1,2-tetrafluoroethane gas and then reseal at the end of the test.
[0142] The various examples and embodiments described herein are illustrative in nature only and are non-limiting of the invention defined by the claims. | A fluid flow control valve comprises (a) a high pressure region adapted to contain a fluid at its supercritical or nearcritical temperature and pressure conditions and connected via an orifice to a low pressure region, (b) a seat adjacent the orifice, (c) a sealing element positionable against the seat to form a seal between the high pressure region and the low pressure region, and (d) an electrically and/or electronically controlled actuator operable to move the sealing element against and/or away from the seat to allow control of fluid flow from the high pressure region to the low pressure region. In a specific embodiment, the high pressure region contains a fluid at its supercritical or nearcritical temperature and pressure conditions. The valve may be used, for example, to provide very low flow rates, for example, for supercritical fluid chromatography, supercritical fluid extraction, critical point drying, supercritical fluid cleaning, and supercritical fluid separation methods. In another embodiment, the valve is suitable for use in methods of delivering a biologically active substance to a patient in need thereof. | 0 |
FIELD OF THE INVENTION
[0001] This invention relates to the field of footwear, more particularly corrective running athletic shoes, designed to provide gait correction, proper shock absorption, and the ability to minimize running injuries.
BACKGROUND OF THE INVENTION
[0002] Running, varying from everyday exercise running to cross country running, track season running and the like, is known to cause repetitive stress injuries, particularly for long distance runners. Injuries may vary from ligament stress, to muscle stress, to actual stress fractures. In fact, reports show that at least 60% of runners are nursing some sort of injury at any given time.
[0003] It has been noticed that in European countries and the USA, most runners are heel strikers, that is they run heel to toe. In contrast, long distance barefoot runners from African nations are frequently forefoot strikers, that is to say they run toe to heel. It has been noticed that many of these African long distance runners, who actually prefer barefoot running (and who run as forefoot strikers) simply do not experience nearly the high level of repetitive stress injuries of heel striking runners.
[0004] There is, however, great difficulty in converting runners from heel strikers to toe strikers. During the correctional period while the runner is attempting to change over to a primary forefoot striker, different muscles are used than normal and pain resulting therefrom usually results in abandonment of the project with the runner returning to the more common heel-strike-first method. Most, if not all current running shoes are designed for heel strikers.
[0005] In the past, there have been some walking shoes that have so-called negative soles, that is to say, the sole is thicker at the toe than at the heel to encourage walking in perhaps a more healthful manner (see for example, U.S. D472,038 and U.S. Pat. No. 6,578,290). These shoes, however, sold under the trademark Earth® Shoes are not designed for athletic use, nor are they designed as a correctional shoe to encourage and enforce forefoot striking first running
[0006] It is a primary objective of this invention to provide a correctional shoe that encourages a runner to land in the neighborhood of the tarsal-metatarsal joint, i.e., approximately at the base of the toes. The difference in the correctional shoe and shoes such as Earth® Shoes is that the correctional running shoe is more aggressively designed with the front of the shoe actually thicker than the heel and with specially designed flexible struts in the arch or midsole section, all to encourage the runner to touch down the toe first instead of the heel.
[0007] Another primary objective of the invention is to provide a corrective shoe that is more effective than any before for converting a heel striker to a toe striker, all with less muscle stress and ligament stress during the corrective period.
[0008] An even further objective of the present invention is to use force deflecting struts in the mid sole area or arch area of a running shoe in order to provide maximum flexibility in the mid sole area under the arch of the wearer's foot.
[0009] This shoe therefore differs considerably from regular standard heel to toe drop on regular running shoes, which is usually ½″ making it difficult to hit the heel portion of the shoe first, and making it easier for runners who wear such a shoe and to convert themselves to the barefoot style of toe strike first.
SUMMARY OF THE INVENTION
[0010] The present invention relates to a correctional shoe designed to force a toe/heel running gait. The shoe has a conventional upper but a negative sole having a heel portion, a midsole portion, and a toe portion, all made from cushioned sole material. The heel portion has about ⅙ to about ⅓ less thickness than the toe portion, and the mid sole portion has a force deflector strut or struts to provide a maximum, flexible mid sole arch area under the wearer's foot. The result is a shoe which can be comfortably worn during training of a runner to be a toe striker rather than a heel striker without the usual stress of joints, ligaments, and muscles from wearing conventional heel strike running shoes while trying to retrain to a toe striker.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIG. 1 is a perspective view of a typical correctional shoe of the present invention.
[0012] FIG. 2 is a drawing showing gait rest posture line of a person wearing the negative sole correctional shoe.
[0013] FIG. 3 is a side view of the sole of the present invention.
[0014] FIG. 4 is a bottom plan view of the sole of the present invention.
[0015] FIG. 5 is a bottom perspective view of the sole with the incorporated midsole struts for maximum arch flexibility.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0016] Referring to FIG. 1 , it shows a side view of a shoe 10 of the present invention having an upper 12 and a cushioned sole 14 . The cushioned sole 14 is made of conventional running shoe cushioning materials. For example, the sole may include or be made from Ethyl Vinyl Acetate (EVA), some portions of it, such as an outer sole made from rubber. Suitable soles and sole constructions for use as sole 14 are illustrated in U.S. Pat. No. 6,026,593, which is incorporated herein by reference. This invention is not the polymeric cushion sole material, but the construction or design of it.
[0017] FIG. 2 shows the sole 14 of the present shoe under the foot of a person 16 to show the effect on the posture line 18 . As can be seen, the sole 14 is a so-called negative sole, that is to say it is lower at the heel 20 than at the toe portion 22 . The result of this is a natural standing posture, as illustrated in FIG. 2 .
[0018] FIGS. 3 and 4 show respectively a side view of the sole only and in FIG. 4 , a plan view of the sole only. As shown, the sole 14 has a negative tilt to it. The heel portion 20 can generally have a thickness of 20 mm to 30 mm, preferably 20 mm to 25 mm. The toe portion 22 of the correctional shoe 10 can generally have a thickness of from about 30 mm to 45 mm, preferably 30 mm to 35 mm.
[0019] Importantly, in order to provide flexibility in the arch area at a maximum level, the midsole 24 has at least two struts, here three, 26 , 28 , and 30 (three depicted) embedded in the midsole 24 and oriented along the long axis of the shoe 10 .
[0020] The struts 26 , 28 , and 30 can be rib-like structures, c-shaped from a side view, s-shaped from a side view, or smooth or wavy, as deemed most appropriate. Generally, this provides enhanced flexibility, i.e., the strut as seen from a side view has curvature providing a spring like action.
[0021] FIG. 5 shows a bottom perspective view of the shoe and its sole with like parts similarly numbered.
[0022] Some shoes may rather than use actual struts, currently available in the market, use impact air cushions in a similar manner to absorb shock and provided deflection and cushioning. These may be used in lieu of actual physical struts but serve the same purpose. As used herein, the term force deflection struts is defined to include impact air cushions, shock cushions, and as well struts springs or any other deflection enhancing material embedded in the arch area of the sole 14 , including an embedded different polymer material from the rest of the sole.
[0023] When the shoe is placed on the human wearer's foot and the person stands as indicated at 16 , the posture line 18 is automatically assumed. When running, the person will find it almost impossible to do anything but running toe strike first. For anything else they must assume awkward positions and/or risk tumbling. The impact area under the arch (i.e., midsole portion) provides enhanced flexibility to cushion and shock, lessening the strain in retraining the body and naturally more spring in the foot and ankle area, and less heel impact shock.
[0024] Like barefoot running, the corrective shoe encourages a fast cadence, focusing on lifting of your feet before landing, and a natural body bend to take advantage of the natural shock absorption of ankles, knees, and hips when the body is bent. Moreover, the muscles of the legs and calves are gradually corrected without the usual immediate soreness and pain caused by switch over from heel strike to toe strike.
[0025] It therefore can be seen that the shoe accomplishes at least all of its stated objectives. | A correctional running shoe with an upper shoe attached to a negative sole having a heel, a specially designed flexible midsole, and a toe portion, all made from cushioned material. The heel has at least about 1/6 to about 1/3 less thickness than the toe portion so that the foot naturally rests with the toe inclined and the heel downward. | 0 |
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation-in-part of our copending application Ser. No. 636,801 filed Dec. 1, 1975, now abandoned.
This invention relates to organic polymers containing tri(phenylene disulfide) or biphenylenedisulfide nuclei and to crosslinked forms of the tri(phenylene disulfide) polymers. The invention also relates to methods of producing such polymers.
CROSS REFERENCE TO RELATED APPLICATION
This application is related to our copending application Ser. No. 479,983, now U.S. Pat. No. 3,907,748.
BACKGROUND OF THE INVENTION
Filled resins, e.g., glass fiber and fabric reinforced resins, are well-known as suitable materials for forming structural units in the aircraft and other industries. A wide variety of resins have been proposed in the past for formulating such structures and as laminating resins for joining various materials. For example, polyester, epoxy and polycarbonate resins have been utilized as matrix resins for glass fiber-resin laminates. One of the difficulties experienced in the use of these resins, however, is that they are difficult to mold and mechanically work. Thus, it is often necessary to apply the resin in liquid form to the glass fibers or substrate to be laminated and then solidify the composite in order to obtain a suitable product. The resins previously used have to be melted or dissolved in a suitable solvent in order to achieve the desired liquid form. Many of these resins, however, decompose or suffer some deleterious chemical change when heated to temperatures sufficiently high to achieve melting. The result is a laminate or reinforced resin with reduced strength and physical properties.
Moreover, many of the previously used resins are insoluble in conventional volatile solvents. In addition, when forming laminates with solvent solutions of resins, it is necessary to employ special means for driving off and collecting those solvents which are capable of dissolving the resins but are relatively non-volatile.
In addition, the prior art matrix and laminating resins do not possess a sufficiently high degree of thermal stability which is requisite in many industrial applications.
It has been heretofore proposed to provide low melting laminating polymers. These polymers may be melted at low temperatures, contacted with the filler material or substrate to be laminated and cured or cross-linked to the resinous state. A serious disadvantage associated with these low-melting polymers, however, is that cross-linking involves a chemical reaction which liberates a volatile by-product such as carbon dioxide or water. The liberation of these reaction products operates to form voids in the resulting product. Obviously, the prior art low-melting laminating polymers may not be used in applications requiring close tolerance or uniform compositions throughout.
It is an object of the invention to provide low-melting polymers which may easily be admixed with fillers or contacted with substrates to be laminated and cross-linked to form a firmly bonded article having a uniform composition throughout.
It is a further object of the invention to provide novel reinforced and laminated resin compositions having high degrees of strength and thermal stability.
It is another object to provide low-melting polymers which may be cross-linked without the production of volatile materials.
SUMMARY OF THE INVENTION
The above and other objects and advantages are achieved by providing polymers containing a cyclic trimeric disulfide or a biphenylene disulfide. Para and meta cyclic trimeric disulfides corresponding to formulas I and II of the drawing are prepared by oxidation of p-phenylenedimercaptan and m-phenylenedimercaptan, respectively. The polymers of the present invention are produced from a tri(phenylene disulfide) monomer, such as tri(1,4-phenylene disulfide) or tri(1,3-phenylene disulfide), or a biphenylenedisulfide, such as biphenylene-2,2'-disulfide; and a polyaryl ether such as diphenyl ether, or a polyaryl ether sulfone such as 1,3-bis(p-phenoxybenzenesulfonyl)benzene or 4,4'-bis(p-phenoxybenzenesulfonyl)diphenyl ether, by Friedel-Crafts polymerization with isophthaloyl or terephthaloyl chloride. The dibasic phthaloyl moieties link the tri(phenylene disulfide), or biphenylenedisulfide, polyaryl ether, and/or polyaryl ether sulfone molecules together in polymers with molecular weights usually in the range of from about 15,000 to 20,000 although such polymers can exist with molecular weights as high as about 50,000. The polymers so produced are relatively low melting and are suitable for lamination. The polymers containing tri(phenylene disulfide) are readily cured or cross-linked by heating at relatively low temperatures to produce strong infusible resins. The curing temperature can be on the order of 300° C with best cures obtained at 375° C for a period of time in the range of 1-2 hours. The cured polymers are moderately heat stable in air at 300° C.
The polyaryl ether is broadly a compound of the general formula ##STR1## In said general formula, Ar represents a bivalent aromatic radical such as phenylene, naphthylene, and analogous bivalent radicals derived from aromatic compounds such as toluene, xylene, anthracene, fluorene, phenanthrene, acenaphthene, xanthene, pyrene, bis-(benzenesulfonyl)benzene (meta and para isomers), diphenyl sulfone, phenyl naphthyl sulfone, bis-(benzenesulfonyl)toluene, bis-(benzenesulfonyl)naphthylene, dinaphthyl sulfone, and related aromatic compounds. Preferred is the simplest polyaryl ether, diphenyl ether (III).
The weight percentages of the various components in the polymers can vary over fairly wide ranges and still provide useful products, as set forth below:
______________________________________ Useful PreferredComponent Percentage Percentage______________________________________Tri(phenylene disulfide) 2-20 3-6Diphenyl ether 10-65 15-50Polyaryl ether sulfone 25-75 40-60Biphenylene disulfide 5-20 10-15Phthaloyl radical 20-60 25-45______________________________________
When the tri(phenylene disulfide) polymers of the present invention are cross-linked while in contact with a filler or substrate to be laminated, the result is a product having a high degree of strength and thermal stability wherein the cross-linked polymer is firmly adhered to the filler or substrate.
BRIEF DESCRIPTION OF THE DRAWING
Reference is made to the attached drawing illustrating by structural formula some of the separate molecular units includable in the polymers of the present invention. It is understood that when attached to other units of the polymer, interior molecular units will have two less hydrogen atoms and end (terminal) units will have one less hydrogen atom because of the bonds connecting the units. In the drawing, I represents the para-trimeric disulfide isomer, or tri(1,4-phenylene disulfide), which constitutes the cross-linking nucleus in the polymers of the present invention. The meta-isomer II, or tri(1,3-phenylene disulfide), is also useful for the cross-linking nucleus or as a portion of the cross-linking nucleus of the polymers of the present invention. A polyaryl ether, such as diphenyl ether III, and/or a polyaryl ether sulfone, such as 1,3-bis(p-phenoxybenzenesulfonyl)benzene V, or 4,4'bis(p-phenoxybenzenesulfonyl)diphenyl ether VI, also forms a portion of the polymers of the present invention. The intermediates for the polymers are isophthaloyl or terephthaloyl chloride IV (both iso' and tere' isomers are indicated by showing a bond between the ortho and meta positions on the benzene ring). The biphenylene-2,2'-disulfide unit VII can replace the tri(phenylene disulfides) I and II in producing polymers in accordance with the present invention.
In accordance with a preferred embodiment of the present invention, a tri(phenylene disulfide) monomer (I and/or II) is reacted with a polyaryl ether, such as diphenyl ether III, and one or more polyaryl ether sulfone molecules, such as V and/or VI, are joined by Freidel-Crafts polymerization with one or more of the isomeric acid chlorides IV. The polymers are made up of combinations of I and/or II, III and at least one of V and VI with phthaloyl radicals IV interconnecting them. The sequence of the I (and/or II), III, V and/or VI moieties is random with IV interconnecting them. For example, the polymer can be illustrated as follows:
-- I--IV--III--IV--V--IV--I--IV--III--IV--V--IV --.sub.n
which is a regular sequence, or as follows:
-- I--IV--V--IV--VI--IV--III--IV--III--IV--II--IV --.sub.n
which is random, or as follows:
-- I--IV--II--IV--III--IV--VI--IV--II--IV--III--IV --.sub.n
or,
-- I--IV--III--IV--I--IV--III--IV--I--IV--III--IV --.sub.n
In the above formulas, n represents a number from about 4 to about 17.
It should be recognized that at each I or II location, there are three sites (S--S bonds) for attachment of other moieties and, generally, the polymers can react at each of these sites so that the polymers are generally non-linear.
In accordance with another embodiment of the present invention, the biphenylene-2,2'-disulfide molecule(VII) replaces some or all of the tri(phenylene disulfide) molecules in the above described polymerization reactions and in the polymerizations described in the examples to follow.
DETAILED DESCRIPTION OF THE INVENTION
In one preferred form of the invention, the polymer is made up of I and III linked together in random sequence by iso- and/or terephthaloyl radicals IV. In another form of the invention, the polymers of the present invention are produced from II and III linked together with iso- and/or terephthaloyl radicals IV. In another form of the invention, the polymer is produced from I and/or II and III and V linked together in random sequence with isophthaloyl and terephthaloyl radicals IV. In another form of the invention, the moieties V of the above polymers can be substituted by the moiety VI or a portion of the moieties V can be replaced by the moiety VI. The quantity (moles) of iso- and/or terephthaloyl radicals is approximately equivalent to the total moles of I, II, III, V and VI. The quantity of iso- and/or terephthaloyl radicals generally lies in the range of 0.8 to 1.2 moles per total moles of I, II, III, V, VI and VII. The polymerization is carried out in the presence of anhydrous aluminum chloride in an inert solvent.
Aromatic ethers and sulfones are known to be thermally quite stable. Consequently, polymers containing these functional groups and incorporating trimeric disulfide (I or II) units or biphenylene disulfide (VII) units are materials of great potential as high temperature-resistant laminating resins.
EXAMPLE 1
A. Synthesis of tri(1,4-phenylene disulfide): I
A solution of 2 grams of p-phenylenedimercaptan in 500 ml of 95% ethanol and a solution of 3.5 grams of iodine in 500 ml of 95% ethanol were added dropwise simultaneously into a 2-liter beaker containing 1-liter of 95% ethanol and 5 ml of conc. hydrochloric acid. The solutions were added at opposite sides of the beaker to achieve the effect of high dilution. After all of the p-phenylenedimercaptan had been added, a slight excess of iodine solution was introduced to insure complete oxidation and the excess of iodine was then removed by adding sodium bisulfite. A white precipitate of polymeric material was filtered off and the solvent was evaporated. After most of the solvent had been removed the remaining solution was cooled and 0.6 grams of yellow crystals separated. After washing with water and drying under reduced pressure, the tri(1,4-phenylene disulfide) melted at 150°-152° C. The mass spectrum showed a molecular weight of 420.
Analysis: Calculated for C 18 H 12 S 6 : C, 51.43%; H, 2.86%; S, 45.72%. Found: C, 51.25%; H, 2.92%; S, 45.70%.
B. Synthesis of tri(1,3-phenylene disulfide): II
In a similar procedure to that above, 6 grams of m-phenylenedimercaptan was oxidized to 4 grams of light yellow crystals. The mass spectrum showed a molecular weight of 420, the same as the calculated molecular weight. The tri(1,3-phenylene disulfide) had a melting point of b 153°-155° C.
Analysis: Calculated for C 18 H 12 S 6 : C, 51.43%; H, 2.86%; S, 45.72%. Found: C, 51.62%; H, 2.98%; S, 45.87%.
EXAMPLE 2
A. Synthesis of 1,3-Bis(p-phenoxybenzenesulfonyl)benzene: V
To a solution of 137.0 grams (0.498 mole) of m-benzenedisulfonyl chloride in 170 grams of diphenyl ether was added 1.0 gram of ferric chloride. The reaction was stirred at 170° C for 24 hours. After the reaction had cooled to room temperature, ethyl ether was added and the mixture was filtered and washed with water. The ether layer was separated, filtered, and dried over Na 2 SO 4 . Evaporation of the ether and distillation of diphenyl ether under reduced pressure afforded a crude solid. The crude product then was distilled under high vacuum (0.1mm) with an open flame. The distillate solidified upon cooling and was dissolved in 40 ml of chloroform and 800 ml of ethyl ether. A small amount of insoluble black residue was filtered from the solution. The addition of 800 ml of petroleum ether precipitated 160 grams (63%) of a white powder, mp 70°-75° C.
B. Synthesis of 4,4'-Bis(p-phenoxybenzenesulfonyl)diphenyl ether: VI
To a solution of phenoxybenzene-4,4'-disulfonyl chloride (60 grams, 0.163 mole) in 400 ml of dry diphenyl ether (429.2 grams, 2.52 mole) was added 3.0 grams of ferric chloride. The mixture was stirred under nitrogen and heated to 160°-165° C for 48 hours. The cooled suspension was filtered free of ferric chloride and petroleum ether (500 ml) was added to precipitate a brown solid. The resultant precipitate was filtered and then extracted in a Soxhlet for 10 hours with 800 ml of methanol. The material not extracted by methanol was dissolved in chloroform and then passed through a short (25 cm) alumina column. Concentration of the chloroform and the addition of petroleum ether precipitated 53.4 grams (52%) of a white solid, mp 196°-200° C.
EXAMPLE 3
Synthesis of Biphenylene-2,2'-disulfide:
The procedure of Barber and Smiles, as set forth in J. Chem. Soc., 1441 (1928) as modified by the Allen, et al. procedure, J. Chem. Soc., (C), 3454 (1971), was used for this preparation. The crude product (mp 110°-113° C) was recrystallized from hot 95% ethanol. mp 113°-114° C.
Analysis: Calculated for C 12 H 8 S 2 : C, 66.67%; H, 3.70%; S, 29.63%. Found: C, 66.63%; H, 3.84%; S, 29.53%.
POLYMERIZATIONS
The polymerizations of the following Examples 4-8 were run under anhydrous conditions in a nitrogen atmosphere at room temperature using equivalent amounts of isophthaloyl chloride and other monomers. The reactants were dissolved in dichloroethane solutions under stirring. Aluminum chloride catalyst was then added. The polymers gradually precipitated during the reaction.
EXAMPLE 4
Polymerization of Polymer A (Table I)
Tri(1,4-phenylene disulfide) [0.1512 grams or 0.360 millimole (mM)], diphenyl ether (1.5716 grams or 9.468 mM) and isophthaloyl chloride (1.9951 grams or 9.828 mM) were dissolved in 70 ml of 1,2-dichloroethane. Aluminum chloride (4 grams) was then added. The mixture was stirred at room temperature for 48 hours under nitrogen. The precipitated polymer was filtered, washed with methanol four times in a blender, and dried under vacuum at 80° C. A pale yellow powder (2.1 grams) was obtained. This polymer is indicated as polymer A in Table I. The polymer contained a small amount of alumina as indicated by the residue on combustion.
EXAMPLE 5
Preparation of Polymer B (Table I)
Tri(1,4-phenylene disulfide) (0.1000 gram or 0.238 mM), diphenyl ether (0.3348 gram or 1.9694 mM), 1.3-bis(p-phenoxybenzenesulfonyl)benzene (1.9694 mM) and isophthaloyl chloride (0.8727 gram or 4.299 mM) were dissolved in 55 ml of dichloroethane. Aluminum chloride (2.2 grams) was then added. The mixture was stirred at room temperature for 3 days under nitrogen. The precipitate was filtered and washed four times with methanol in a blender, then dried at 80° C under vacuum. A pale yellow powder (1.43 grams, 72% yield) was obtained.
EXAMPLE 6
Preparation of Polymer C (Table I)
Tri(1,3-phenylene disulfide) (0.1512 grams or 0.360 mM), diphenyl ether (1.5716 grams or 9.468 mM), and isophthaloyl chloride (1.9951 grams or 9.828 mM) were dissolved in 100 ml of 1,2-dichloroethane. Aluminum chloride (4.5 grams) was added. The mixture was stirred at room temperature under nitrogen for 18 hours. Almost no polymer precipitated out. Another portion of aluminum chloride (2.5 grams) was then added. Some polymer precipitated out in one hour. It was stirred at room temperature for another 24 hours. Then another portion of aluminum chloride (2.0 grams) was added. More precipitate was found in 1/2 hour. The stirring was continued until the total reaction time was 72 hours. The solvent was decanted and the polymer was washed four times with methanol in a blender. The yield was 2.75 grams or 92%.
EXAMPLE 7
Preparation of Polymer D (Table I)
Tri(1,3-phenylene disulfide) (0.100 grams or 0.238 mM), diphenyl ether (0.3348 grams or 1.9694 mM), 1,3-bis(p-phenoxybenzenesulfonyl)benzene (1.9694 mM) and isophthaloyl chloride (0.8727 grams or 4.299 mM) were dissolved in 55 ml of 1,2-dichlorethane. The mixture was stirred at room temperature under nitrogen for 63 hours. The solvent was decanted. The polymer was washed three times with methanol in a blender and dried in a vacuum at 60° C. A pale yellow powder (1.53 grams or 77% yield) was obtained.
EXAMPLE 8
Preparation of Polymer E (Table I)
Biphenylene-2,2'-disulfide (0.45 gram or 2.1 mM), 1,3-bis(p-phenoxybenzenesulfonyl)benzene (1.8257 grams or 3.4 mM), and isophthaloyl chloride (1.1125 grams or 5.5 mM) were dissolved in 60 ml of dry 1,2-dichlorethane. Aluminum chloride (3.33 grams) was then added. The mixture was stirred at room temperature under nitrogen for 24 hours. The polymer precipitate was filtered and washed four times with methanol in a blender. It was dried in a vacuum. The yeild was 1.8 grams. It was soluble in dimethylformamide.
TABLE I__________________________________________________________________________POLYMERS A-E of EXAMPLES 4-8 ° C AnalysisMillimole Monomers Soft- Resi-Poly- I or II ening duemer IV (iso) III or VII V ηinh Point C. % H. % S. % %__________________________________________________________________________A 9.83 9.47 0.36 I -- 0.22.sup.a 225-232 Calculated 78.51 3.88 2.30 Found 77.55 3.91 2.01 1.67B 4.30 1.97 0.238 I 1.97 0.23.sup.b 200-215 Calculated 70.70 3.61 8.34 Found 68.62 3.75 8.51 1.74C 9.83 9.47 0.36 II -- 0.23.sup.a 320 Calculated 78.51 3.88 2.30 Found 75.06 3.92 2.45 3.25D 4.30 1.97 0.238 II 1.97 0.23.sup.a 190-210 Calculated 70.70 3.61 8.34 Found 69.29 3.81 8.43 1.00E 5.50 2.1 VII 3.40 0.075.sup. c 173-175 Calculated 68.30 3.40 11.62 Found 64.57 3.49 10.25 2.51__________________________________________________________________________ .sup.a In conc. Sulfuric Acid. .sup.b In hexamethylphosphoric triamide (HMPA) .sup.C In dimethylformamide (DMF)
The isothermal weight losses of these polymers in circulating air at 300° C are shown in Table II.
TABLE II______________________________________ISOTHERMAL WEIGHT LOSS AT 300° C INCIRCULATING AIRPolymer Time (Days) Wt. % loss______________________________________A 9 6.4B 7 11.2C 7 8.9D 7 9.5______________________________________
Polymer A was crosslinked by heating it respectively at 310° C, 350° C and 375° C. Vicat softening curves showed that the best temperature for crosslinking was 375° C. A comparison of Vicat softening curves for polymer A, B, C and D that were crosslinked at the same temperature in the same time showed that polymers A and C had higher rigidity at high temperature, while the rigidities for crosslinked polymers B and D were relatively lower. It also showed that the para cyclic trimer (I) may be easier to open for crosslinking than the meta cyclic trimer (II). Polymers A, B, C and D in Table I are insoluble in cold dimethylformamide (DMF) or in hexamethylphosphoric triamide (HMPA), but somewhat soluble in hot DMF or hot HMPA. After crosslinking they became insoluble in these hot solvents but their IR patterns were similar to those before crosslinking.
Polymer E, containing biphenyl-2,2'-disulfide, 1,3-bis(p-phenoxybenzenesulfonyl)benzene and isophthaloyl chloride showed no crosslinking when it was heated at 360° C for 24 hours. It maintained the same melting point and still dissolved in dimethylformamide. | A tri(phenylene disulfide) polymer composed of para- or meta-tri(phenylene disulfide) units and units selected from the group consisting of diphenyl ether, bis(phenoxybenzenesulfonyl)benzene and bis(phenoxybenzenesulfonyl)diphenyl ether, is linked together with bivalent radicals selected from the group consisting of isophthaloyl and terephthaloyl radicals. In another embodiment, the tri(phenylene disulfide) can be substituted with biphenylene-2,2'-disulfide. | 2 |
BACKGROUND OF THE INVENTION
For some time it has been common to manufacture drinking cups, other containers and plastic sleeves for bottles from expanded thermoplastic materials. A popular material currently in use for containers, etc. is expanded oriented polystyrene. A very popular container of this type is a cup that is molded directly from expandable polystyrene beads in a steam chest. However, cups formed in this manner must have a sidewall that is quite thick in comparison to, for example, paper. The added thickness of a cup formed by the molded steam chest method does not lend itself to a small stacking height, thus more space is required for a stack of a given number of cups. Then too, the inherent mode of manufacture of the steam chested cup prevents it being decorated to any degree until it is completely formed. The decoration of completed cups requires printing techniques that are slower and more expensive than flexographic and other sheet printing techniques employed on sheet stock which is preprinted prior to incorporation into containers or for sleeves used as a protective overwrap on glass containers such as bottles.
This invention is intended for use on plastic sleeve forming machines of the type disclosed in U.S. Pat. No. 3,970,492 issued to S. W. Amberg, et al on July 20, 1976, and U.S. Pat. No. 3,802,942 issued to S. W. Amberg, et al on Apr. 9, 1974. These machines are used to form sleeves from thermoplastic material by forming a rectangular sheet of material into a tubular shape having overlapping end portions and sealing the end portions together. The completed sleeves are then used to form either a thermoplastic cup or a shrink wrap covering for a glass container. In both of the above mentioned U.S. patents the seam is formed by heating the overlapping end portions of a formed tubular shape to soften their facing surfaces and pressing the end portions together to form a seam. The pressing is done by means of bar and results in a slight indentation in the area where the bar contacts the plastic material. The pressing action causes some distortion in the cellular structure of the thermoplastic material, with a resultant deterioration of insulative properties in the seam area. In U.S. Pat. No. 4,013,496 issued to S. W. Amberg on Mar. 22, 1977, the seam is formed by means of a spring loaded roller which presses against the overlapping edges of the tubular sleeve. Since the roller which forms the seam is spring loaded and the seam is formed basically by a pressing action, the thickness of the seam may be different from that of the remainder of the formed sleeve.
SUMMARY OF THE INVENTION
The present invention is directed to a method and apparatus for forming a seam on a cylindrical sleeve of thermoplastic material which has both a uniform thickness when compared to the remainder of the sleeve and whose insulative properties also conform substantially to those of the remainder of the sleeve. This is accomplished by means of a curvelinear sealing plate section positioned at a fixed location along a peripheral path of a series of vertically disposed rotating sleeve forming mandrels mounted on a rotating turret. The overlapping seam edges are heated to fusing temperature and sealed together when the mandrel passes the sealing plate. The curved sealing plate meters a uniform thickness of the material through its arcuate path and a constant ironing or wiping pressure is applied at the seam area, the ironing process results in a uniform bonding of the two surfaces which form the seam. The length of the sealing plate can be such that the mandrel will complete several rotations as it passes by the plate, thus causing the seam ironing process to be repeated several times. The position of the curved sealing plate is adjustable for different material thicknesses, and the thickness of the seam conforms very closely to that of the remainder of the sleeve sheet material. In addition, the wiping process results in minimal disturbance of the cellular structure of the thermoplastic material, thus retaining the insulative properties of the material at the seam location.
BRIEF DESCRIPTION OF THE DRAWINGS
The FIGURE is a perspective view of a sleeve winding apparatus which shows the mandrels and the sealing plate.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 of the drawings shows in general a simplified form the apparatus necessary in order to carry out the present invention. A base for the apparatus is shown at 10. The base 10 provides structure for a mandrel support turret 12 which carries an array of sleeve winding mandrels 14. Immediately adjacent the mandrel support turret is a feed drum 16 that delivers a measured length of plastic sheet material to each one of the sleeve winding mandrels 14.
More particularly, the base 10 provides the necessary structure for the mandrel support turret so that it may rotate about a central pivot 18. The mandrel support turret 12 is positioned so that its deck 20 is generally horizontal and the turret is capable of rotation in either direction. For purposes of this invention, the rotation of the mandrel support turret 12 is in the direction of arrow 22. Also, power to the turret 12 and other moving parts of the apparatus has not been shown since it is well within the skill of the ordinary person to visualize how each part could be powered.
Referring once again to FIG. 1, a web of plastic strip stock 24 is drawn through a pair of opposed feed rollers 26 and 28. The strip stock 24 is then directed around the exterior of a feed drum 16. The strip stock 24 is stabilized and held against the surface 30 of feed drum 16 by means of a vacuum applied through a plurality of vacuum ports 32 which are aligned over the surface 30 of feed drum 16.
As the strip stock moves around feed drum 16, a rotary knife 34 cuts the strip stock 24 into individual rectangular lengths, hereinafter referred to as blanks 36. The severed blank 36 is held against the surface of feed drum 16 by vacuum supplied through ports 32 until the leading edge 38 of blank 36 is in close tangential proximity with a sleeve winding mandrel 14. At this instant, the vacuum beneath the leading edge 38 is reversed to a positive pressure, thus releasing the leading edge 38 so that it may be picked up by the vacuum ports 40 located over the surface of the sleeve winding mandrel 14.
As the sleeve winding mandrel 14 rotates about its own axis by a drive means not shown, the blank 36 is completely transferred from the feed drum 16 to the sleeve winding mandrel 14. After the transfer of the blank 36 has been completed, the trailing edge 42 overlaps the leading edge 38 of blank 36 as shown in the drawings.
A plurality of sleeve winding mandrels 14 is circumferentially located on the top deck 20 of mandrel support turret 12. Each winding mandrel 14 received a blank 36 as the winding mandrel passes the feed drum 16.
As previously stated, the trailing edge 42 overlaps the leading edge 38 of blank 36. Heat is applied to both the inside and outside surfaces of the trailing edge 38 by a blower 44 which is positioned adjacent sleeve winding mandrel 14. While only one such blower 44 is shown in the drawings, it is to be understood that each one of the mandrels 14 has its own blower. A hot gaseous medium such as air is directed toward the trailing edge 42 which protrudes somewhat because it is not being held by the vacuum of mandrel 14. The hot gaseous medium exiting from blower 44 heats not only the exterior surface of trailing edge 42, but also the interior surface as well. In order to assist the hot gaseous medium exiting from blower 44, it is also possible to introduce a solvent spray either through blower 44 or by a separate spray system nearby to aid in conditioning the interior surface of the trailing edge 42 of blank 36 so that it will adhere to the exterior of the surface of leading edge 38.
As the sleeve winding mandrel 14 continues to move in an arcuate path along with the mandrel support turret 12, the mandrel 14 travels past a stationary sealing plate 46. Sealing plate 46 is curvilinear in shape and is mounted in an upright attitude from base 10. Sealing plate 46 is further made adjustable by the adjustment combination shown on adjustment support brackets 48 and 50. The sleeve winding mandrel 14 initially passes by an outwardly curved portion 52 of sealing plate 46 which provides a lead-in for the mandrel 14 and the blank 36 wrapped therearound. As the sleeve winding mandrel 14 continues to translate and rotate, the protruding trailing edge 42 of the blank 36 strikes the surface of sealing plate 46. The trailing edge 42 is firmly worked into the configuration of a cylinder as the mandrel 14 follows the remaining portion of sealing plate 46 which is arcuate in configuration and which is also concentric with the center of revolution of turret 12.
As has been just pointed out, mandrel 14 rotates about its own axis and at the same time, the entire mandrel 14 is being translated in an arcuate path being generated by the movement of the mandrel support turret 12. So long as the mandrel 14 rotation is as shown in the drawings, there will be a sliding or ironing of the blank 36 exterior against the surface of sealing plate 46. It would be possible and is considered within the purview of the present invention to reverse the direction of rotation of the mandrel 14 subsequent to its pickup of blank 36. Faster or slower rotation of mandrel 14 would produce a situation where blank 36 would partially roll and partially slide along the surface of sealing plate 46.
The adjustment brackets 48 and 50 provide for minute adjustments so that during the operation of the apparatus the sealing plate 46 can be held a particular preselected distance from the wall of the mandrel 12 at all points along its arcuate extent. The distance between the surface of the arcuate extent of sealing plate 46 and the external surface of mandrel 14 corresponds to a particular thickness of the plastic material which is utilized for the fabrication of a given sleeve from blank 36. The sealing plate 46 thus serves as a metering function in that only a particular thickness of sleeve material will be allowed to pass by the sealing plate 46 as mandrels 12 move by it. Since the area of the sleeve where the leading edge 38 and trailing edge 42 overlap will be greater than the desired thickness, the temperature or solvent softened material at the overlap of blank 36 will be ironed or wiped to the desired wall thickness of a finished sleeve. The softened ends of blanks 36 are thus caused to be fused together by the ironing effect of curved sealing plate 46.
As the mandrel support turret and its array of sleeve winding mandrels 14 continues to rotate, the finished sleeves are removed from the mandrels 14 by means of an ejector 54 which is positioned around the base portion of each mandrel 14. Once again, only one typical ejector 54 is shown in the drawings.
The finished sleeves are subsequently transferred to other machinery which utilizes the sleeves in affixing a protective wrap around a glass bottle or else utilizes the sleeve in the fabrication of an all plastic container such as a drinking cup. | A sleeve forming apparatus wherein a rectangular sheet of thermoplastic material is formed into a tubular shape having overlapped end portions that are sealed together so as to minimize the lap thickness of the seam. Also disclosed is a method of forming a tubular shape wherein the seam area is worked to minimize its thickness while preserving its liquid-tight characteristics. | 1 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. provisional patent application Ser. No. 61/831,957, filed Jun. 6, 2013, which application is incorporated herein for all purposes.
BACKGROUND
[0002] Many objects periodically need to be relocated in horizontal position (“position”) and/or vertical position (“elevation”), relative to a gravitational field. Table saws need to be repositioned within workshops; shipping containers need to have elevation and position changed; a flower container may need to be relocated on a deck. Some objects never experience a change in elevation or position; some experience one or more generally unrelated changes in elevation and/or position; some experience a cyclic change in elevation and/or position (for example, the objects are cyclically lifted up and down); while some experience change more often in one direction than another.
[0003] Many technologies have been developed over the years to change the position or elevation of objects. Cars and trucks have wheels; fork lifts and cranes can change the elevation of shipping containers; furniture has casters, including retractable casters. These technologies appear to be specific to the application. For example, in the context of retractable casters, patent numbers 2490953, see FIG. 1A , and 2779049, see FIG. 1B , illustrate technologies which require that the object supported by the caster be tilted in a specific direction to engage the caster and then a different direction to disengage the caster; other existing examples, such as the example illustrated in patent number 2663048, see FIG. 1C , require additional parts, such as load-bearing cams or, as in 6507975, require manipulation of an external articulator to engage or disengage the caster.
[0004] Existing technologies, however, often require specific equipment or infrastructure, and/or require that the position and/or elevation changing equipment be manipulated in particular way, and/or require relatively expensive components which must be precisely engineered for the application context and/or which must be maintained over time.
[0005] In addition, existing technologies do not approach the problem from the perspective of a kinematic finite state machine, which can be in a finite number of different states, with transitions between the states caused by triggering events, in which the states define the memory condition of the state machine, the events define how the memory conditions may be processed, where the states are equivalent to logical statements, where there may be an order of the logical statements, and where the state machine may be reprogrammed.
SUMMARY
[0006] A first object and a second object each comprise a surface, each of which defines a coordinate function. The coordinate functions of the first and second objects together form a composite surface defining a composite coordinate function. The composite surface contacts a switch; the switch only moves relative to the first and second objects in response to gravity and acceleration. The first and second objects have an allowed range of motion relative to one another. When the first and second objects move relative to one another within the allowed range of motion, the composite coordinate function transmits a force at a force vector to the switch, which force and force vector may change the position or orientation of the switch in the finite state machine. When certain of such movements pass one or more points of no return, events occur which change the state of the machine. The then-current state and the event determine the state of the finite state machine in the following state. In the states, the switch either i) experiences no more force than the force produced by its own weight on the surface(s) of the object(s) or ii) it contacts both objects and transports a force at a force vector across the two objects, which force is greater than the force produced by the weight of the switch. As used herein, “weight” is defined as mass multiplied by acceleration, whether the acceleration comes from a gravitation field or acceleration due to movement.
[0007] The first object is active; it may be repositioned by an external force. The second object and the switch are passive, reacting to forces provided by the first object. Except for one state, the first and second objects are in a passive kinematic relationship, in which the number of degrees of freedom of motion between the two objects does not change. However, in at least one state, referred to herein as the “engaged” state, the number of degrees of freedom of motion between the two objects is limited by the switch and the switch has zero degrees of freedom of motion. In the non-engaged state(s), the switch does not limit the number degrees of freedom between the first two objects and the switch's number of degrees of freedom of motion is greater than zero.
[0008] For example, in a first state the switch may not be interposed between the objects and the first object may be free to translate vertically and come to rest on, for example, the ground; in another state, the switch may be interposed between the objects such that a reactive force is transmitted through the switch from the second object to the first object, such that the second object supports the first object via the switch, subjecting the switch to a force greater than the force produced by the weight of the switch and limiting the degrees of freedom of both the first object and the switch.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] Certain of the drawings illustrate motion through a flip-book effect. To experience this effect in a PDF, the viewer may set the display resolution to show one complete page per display-page and then hit “page down” or equivalent.
[0010] FIG. 1A to 1C illustrate prior art.
[0011] FIGS. 2 to 133 illustrate elevation and top plan views of a First Embodiment of a kinematic finite state machine, in which the first and second bodies are provided be separate sets of joined plates, in which the first and second bodies have a piston-type relationship and the switch has a round vertical cross section, and show the states and events of this embodiment of the finite state machine as the first body moves.
[0012] FIGS. 134 to 166 illustrate elevation views of a Second Embodiment of a kinematic finite state machine, in which the first and second bodies are connected at two axles and the switch has a non-round vertical cross section, and show the states and events of this embodiment of the finite state machine as the first body moves.
[0013] FIGS. 167 to 177 illustrate a Third Embodiment of a kinematic finite state machine, in which the first and second bodies have a piston-type relationship and the switch has a non-round vertical cross section. Within this group of figures, FIG. 167 illustrates a side elevation view of exploded components of the Third Embodiment, FIG. 168 illustrates a top three-quarter wire frame view of the exploded components of the Third Embodiment, FIG. 169 illustrates a section perspective view of the Third Embodiment with the components assembled and in State One of the state machine, and FIGS. 170 to 177 illustrate elevation views of the Third Embodiment, assembled, and show the states and events of this embodiment of the finite state machine as the first body moves.
[0014] FIGS. 178 to 217 illustrate elevation, close elevation, and top plan views of a Fourth Embodiment, in which the first and second bodies have a piston-type relationship, and show the states and events of this embodiment of the finite state machine as the first body moves.
[0015] FIGS. 218 to 260 illustrate a Fifth Embodiment of a kinematic finite state machine, in which the first and second bodies are connected at an axle, in which there are two switches, neither of which has a round vertical cross section, and show the states and events of this embodiment of the finite state machine as the first body moves.
[0016] FIG. 261 illustrates variations on a Switch, generally a Switch similar to the one illustrated in Embodiment Two.
DETAILED DESCRIPTION
[0017] As used herein, a kinematic finite state machine comprises at least two bodies and a switch. For the sake of convenience, the first body may be referred to herein as “a Housing” while the second body may be referred to herein as “a Platform”. Each body may be one continuous structure or may comprise multiple bodies or plates permanently or at least semi-permanently joined together to form one continuous structure. As used herein, permanently or semi-permanently joined bodies, or “joined bodies” or “joined plates”, are bodies requiring tools (including hand tools) or removal of a pin or the like to disassemble the joined parts. As discussed herein, the Housing may be part of or may be attached to a “solid body”, such as a table, chair, shipping container, refrigerator, or the like.
[0018] As used herein, the Housing is supported against gravity (and/or against another acceleration force) by i) an external surface, ii) the switch which transfers the weight of or other forces from the Housing to the Platform and then by the Platform to the external surface (potentially via an accessory), or iii) by an external force provided by a human, a fork lift, a crane, or another machine. The Housing may move relative to the Platform and relative to an external surface, upon which the Platform may rest. Motion of the Housing is generally described in terms of one degree of freedom, such as up/down or rotation about an axis, though additional degrees of freedom may also be utilized. The Housing discussed herein is described as an active component, because the position of the Housing is actively changed by the external force.
[0019] As discussed herein, an active component acts on a passive component, such as when a Housing is actively translated or rotated by an external force.
[0020] As discussed herein, prismatic kinematic pairs may act upon a Switch. As discussed herein, revolute kinematic pairs act upon the Platform in the kinematic chain.
[0021] As used herein, the Platform is supported against gravity (and/or against another acceleration force) by an external surface and/or by a joint or revolute kinematic chain with the Housing, when the Housing and Platform are connected by an axle. Between the Platform and the external surface may be an “accessory”, such as, for example, a leg, a wheel-axle combination, an adjustable length leg, a scale, a vibration dampener and the like. Many accessories may be used in addition to these examples. The Platform discussed herein is a passive component, because the Platform only moves, if at all, in reaction to movement of the Housing by the external force.
[0022] The Housing and/or Platform may comprise a Housing-Platform restraint to limit the range of motion between the Housing and Platform and to prevent the Housing and Platform from traversing beyond the allowed range. The Housing-Platform restraint may allow the Housing and Platform to move in a piston-type relationship, wherein a gap (within allowable tolerances) between the Housing and Platform allow the Housing to raise and lower relative to the Platform. The Housing-Platform restrain may comprise a hinge, which causes the Platform to rotate about the hinge when the Housing is raised. The Housing may be lifted vertically, without a rotational component, or the Housing may be lifted by rotation about a corner.
[0023] The Housing and/or Platform together form a composite coordinate function in a variable surface which contacts the Switch and which transmits a force at a force vector determined by the Switch and the Switch geometry. The Housing, Platform, and Switch system may occupy states, which states are changed by events. The Platform may be secured to accessories.
[0024] As used herein, the “switch” is a rigid body in contact with the Housing and/or Platform. The switch either i) experiences no more force than the force produced by its own weight on the surface(s) of the object(s) or ii) when the kinematic state machine is in the engaged state, the switch contacts both first and second objects and transports a force at a force vector across the two objects, which force is greater than the force produced by the weight of the switch. In the engaged state, the number of degrees of freedom of motion between the two objects is limited by the switch and the switch has zero degrees of freedom of motion. In the non-engaged state(s), the switch does not limit the number degrees of freedom between the first two objects and the switch's number of degrees of freedom of motion is greater than zero.
[0025] FIGS. 2 to 133 illustrate elevation and top plan views of a First Embodiment 100 of a kinematic finite state machine, in which the first and second bodies are provided be separate sets of joined plates, in which the first and second bodies have a piston-type relationship and the switch has a round vertical cross section, and show the states and events of this embodiment of the finite state machine as the first body moves. In the First Embodiment 100 , the kinematic pairing between the first and second bodies imposes five constraints on the degrees of freedom in relative movement between the bodies; because unconstrained bodies have a maximum of six degrees of freedom (three translational degrees: up, down, side-to-side; and three rotational degrees: roll, yaw, pitch), constraints on five degrees leaves one degree of freedom. In the First Embodiment 100 , the kinematic pairing is prismatic.
[0026] In FIGS. 2 through 133 , elements 1 through 9 illustrate a set of joined plates comprising the Housing. The plates comprising the Housing may be joined by screws, bolts, nails, glue, epoxy, or the like (not shown in FIGS. 2 through 133 ). In FIGS. 2 through 133 , elements 11 through 16 illustrate a set of joined plates comprising the Platform. Similarly, the plates comprising the Platform may be joined by screws, bolts, nails, glue, epoxy, or the like (not shown in FIGS. 2 through 133 ). The Housing and Platform plates are arranged in a matrix which allows the Housing and Platform to translate vertically relative to one another, but which does not allow the Housing and Platform to translate horizontally relative to one another (movement of the Housing in the horizontal plane will also move the Platform). The plates of the Housing form a first coordinate function, while the plates of the Platform form a second coordinate function.
[0027] Together, the first and second coordinate functions form a variable composite coordinate function. As the Housing is lifted, the variable composite coordinate function transmits forces at force vectors to Switch 10 , which vectors are determined by Switch 10 , generally orthogonal to the slope of the points where the composite coordinate function contacts the Switch. The forces and force vectors trigger events which change the state of this First Embodiment 100 of the state machine. As described further below, these figures show the states and the triggering events of this embodiment of the finite state machine.
[0028] In FIGS. 2 through 133 , element 10 illustrates Switch 10 , in this First Embodiment 100 a rod, such as a one-half inch diameter steel rod (other materials may be used). As illustrated in FIGS. 2 through 133 , the Housing and Platform may move separately. In the illustrations of FIGS. 2 through 133 , the Platform is generally resting on an external surface, while the Housing may rest upon the external surface, but may also be lifted, translating the Housing vertically.
[0029] Proceeding clockwise around FIG. 2 as an example of all of FIGS. 2 through 133 , starting in the top-left quadrant, the top-left quadrant illustrates a top plan view of the First Embodiment 100 , illustrating the plates which comprise the Housing and the Platform, with a width corresponding to the bottom-left quadrant. Among other features, this top-left quadrant illustrates, with pointer and ruler, how the center line of Switch 10 translates horizontally as the displacement of Housing changes relative to Platform.
[0030] The top-right quadrant illustrates a detailed side-elevation view of the First Embodiment 100 , looking down the length of the center line of Switch 10 . Except for FIG. 2 , the top-right quadrant illustrates only those portions of the plates in contact with the Switch 10 .
[0031] The bottom-right quadrant illustrates a front or rear elevation view of the First Embodiment 100 , illustrating the plates which comprise the Housing and the Platform and the Switch 10 . Among other features, this bottom-right quadrant illustrates, with pointer and ruler, how the center line of Switch 10 translates vertically as the displacement of Housing changes relative to Platform.
[0032] The bottom-left quadrant illustrates a side elevation view of the First Embodiment. The bottom-left quadrant illustrates, with broken lines, the perimeter of the Platform and an accessory (a wheel) attached to the Platform.
[0033] Both bottom quadrants illustrate, with pointers and rulers, elevation-view displacement meters.
[0034] In the top-left and bottom right-quadrants in these Figures, plates in contact with and transmitting a force vector to or receiving a force vector from the switch are cross-hatched.
[0035] In all of these views, a force is transmitted to Switch 10 from the Housing. The force has a magnitude, generated by the rate of the relative displacement of the Housing and Platform, and a force vector orthogonal to the slope of the points where the composite coordinate function of the surfaces of the Housing and Platform contact the Switch.
[0036] FIGS. 2 through 133 illustrate the following states and events:
[0000]
TABLE 1
State
Next
State narrative
Event
State
One
a. Raise Housing to displacement 0.10,
One
Housing supported by external surface; Switch in
then lower (FIG. 29)
intermediate energy level, between first energy
b. Raise Housing to displacement 0.28+
Two
well and energy barrier; FIGS. 2 and 133
(FIG. 30+), but less than displacement
2.4 (FIG. 66), lower Housing to
displacement 0.0 (FIG. 42)
c. Raise Housing to displacement 2.5+
Three
(FIG. 67), but less than displacement
3.38 (FIG. 74)
d. Raise Housing to displacement 3.38+
Four
Two
e. Raise Housing to displacement 2.4
Two
Switch falls to First Energy Well (FIG. 36);
(FIG. 66), then lower to 0.0 (FIG. 42)
Housing supported by Switch, Switch supported
c. Raise Housing to displacement 2.5+
Three
by Platform (FIG. 42)
(FIG. 67), but less than 3.38 (FIG. 74)
d. Raise Housing to displacement 3.38+
Four
Three
d. Raise Housing to displacement 3.38+
Four
Switch in or will return to second energy well
f. Lower Housing to displacement −2.5
One
(FIG. 70); Housing supported by external
force; Switch supported by Housing; Platform
supported by external surface
Four
f. Lower Housing to displacement −2.5
One
Switch in or will return to second energy well
when Housing released; (FIG. 70); Housing
supported by external force; Switch supported by
Housing; Platform supported by Switch; FIGS.
2 and 133
[0037] States Three and Four in the foregoing require an external force to support the Housing (such as a human, a fork lift, a crane, or similar). When the external force is removed following the event, then States Three and Four return to State One. If events which do not pass a point-of-no-return are removed, then the table of states and events is reduced to the following:
[0000]
TABLE TWO
State
Event
Next State
One
b.
Two
One
c.
One
One
d.
One
Two
c.
One
Two
d.
One
[0038] In the foregoing, when the machine is in State One, one event, Event b, can transition the machine to State Two. In the foregoing, when the machine is in State Two, two events, Event c and d, can transition the machine to State One. Events b, c, and d are points of no return. FIG. 2 through 133 illustrate two energy wells into which the Switch 10 may fall, if allowed by the composite coordinate function defined by the Housing, the Platform, and Switch 10 geometry. The Switch 10 is illustrated in the first energy well in FIGS. 36-53 ; the Switch 10 is illustrated in the second energy well in FIGS. 70 and 71 and 79 - 112 . The energy wells are separated by an energy barrier defined by the plates comprising the Platform; the Switch 10 obtains energy to move over the energy barrier from the Housing and the force and force vector transmitted to the Switch 10 by the Housing and the Platform. Because the Housing is active, the force for surmounting the energy barrier is provided by the Housing. The Switch 10 may be intermediate between an energy well and the energy barrier, as in State One.
[0039] In FIGS. 2 through 133 , the Housing is in a static kinematic relationship with the Platform. The Housing has two frames of reference: i) the Housing's location in a larger physical body in which the Housing may be embedded (if any) and ii) the horizontal axis of the center of gravity of the Switch 10 .
[0040] In FIGS. 2 through 133 , the Platform has three frames of reference: i) the Housing, determined by the Platform's kinematic pair relationship with the Housing; ii) the vertical axis through the center of gravity of the Switch 10 ; and iii) the kinematic pair relationship with the external surface, which may be mediated by the accessory.
[0041] In FIGS. 2 through 133 , the Switch 10 has one frame of reference: its own center of gravity.
[0042] FIGS. 134 to 166 illustrate elevation views of a Second Embodiment 200 , in which a first body or Housing 201 is attached to a second body or Platform 202 at a Platform-Housing Axle 204 , which bodies combine with a Switch 206 to form a composite coordinate function. Components illustrated and labeled on one side of the Second Embodiment 200 are mirror images of equivalent components on the other side of the Second Embodiment 200 . The bottom portion of FIGS. 134 to 166 illustrates an entire mechanism, which may be embedded in a larger object. The top portion of FIGS. 134 to 166 illustrates a detailed view of the bottom portion. The Housing 201 and Platform 202 are illustrated as being singular components; however, they could be made from a set of plates, as illustrated in the First Embodiment 100 in FIGS. 2 through 133 . In the Second Embodiment 200 , the kinematic pairing between the first and second bodies imposes five constraints on the degrees of freedom in relative movement between the bodies. In the Second Embodiment 200 , the kinematic pairing is revolute.
[0043] In FIGS. 134 to 166 , Housing 201 may translate vertically. The vertical translation of the Housing 201 may have a rotational component; for example, in FIGS. 134 to 166 , the Housing 201 is raised at one corner while the opposite corner remains on the exterior surface, which results in rotation of the Housing 201 about the opposite corner on the exterior surface. Raising the Housing 201 (with or without a rotational component) results in rotation of the Platform 202 about the Platform-Housing Axle 204 , and which changes the composite coordinate function, which, via the Cut-Out 208 (which is part of the Housing) and the Switch 206 , triggers the events which change the states available to the state machine.
[0044] As described further below, FIGS. 134 to 166 show the states and the triggering events of this embodiment of the finite state machine. The Switches 206 in FIGS. 134 through 166 are not round about their horizontal axis of rotation (when viewed in elevation, as in FIGS. 134 through 166 ). The Switches 206 may be connected at their base to the Platform 202 (such as about an axle, not shown).
[0045] The composite coordinate function is formed by the Cut-Out 208 (which is part of the Housing 201 ), the base of the Platform 202 (which changes elevation slightly when the Platform 202 rotates about the Platform-Housing Axle 204 ), and the Switch 206 . The composite coordinate function defines two energy wells, a first well when the Switch 206 is leaning on the left side of the base of the Switch 206 (relative to the Switch 206 on the left side of the machine— FIGS. 134 to 141 ), a second well when the Switch 206 is leaning on the right side of the base of the Switch 206 , and an energy barrier when the Switch 206 is vertically oriented above its base. The energy barrier and the two wells arise because the energy of the Switch 206 is highest when the Switch 206 is vertically oriented above its base. The energy wells and energy barrier are discussed further below in relation to the states available to the finite state system.
[0046] The Platforms 202 in FIGS. 134 through 166 are connected to the Housing 201 at Platform-Housing Axle 204 . The Platforms 202 may be within an opening inside of the Housing 201 . The Switches 206 comprise a Rod 209 , or similar, which Rod 209 projects beyond the main body of the Switch 206 and contacts the Housing 201 along Cut-Out 208 . The Cut-Out 208 , the Platform 202 , and the Switch 206 are configured to impart energy—force—and a direction—vector—to the Switch 206 as the Housing 201 is raised, transitioning the Switch 206 from one energy well to the other, over the energy barrier. The Housing 201 may be raised vertically, holding the Housing 201 horizontal as it is raised, and/or it may be raised vertically by rotating the Housing 201 about an axis, such as a corner of the Housing 201 (as illustrated in FIGS. 134 to 166 ).
[0047] In all of these views, a force is transmitted to the Switch 206 from the Housing; the force has a magnitude, generated by the rate of the relative displacement of the Housing and Platform, and a force vector orthogonal to the slope of the combined coordination functions of the surfaces of the Housing and Platform where they contact the Switch.
[0048] FIGS. 134 through 166 illustrate the following states and transitions:
[0000]
TABLE THREE
State
Next
State narrative
Event
State
One
a. Raise Housing 201 to elevation less
One
Housing 201 supported by external surface;
than in FIG. 140 (approximately shown
Switch 206 in intermediate energy level, between
in FIG. 139), then lower
first energy well and energy barrier; FIGS. 134
b. Raise Housing 201 to elevation greater
Two
and 166
than in FIG. 139, but less than
equivalent elevation in FIG. 151, then
lower
c. Raise Housing 201 to elevation in
Three
FIG. 151+, less than elevation in FIG.
153+
d. Raise Housing 201 to elevation in
Four
FIG. 153+
Two
e. Raise Housing 201 to elevation less
Two
Switch 206 falls to bottom of first energy well
than in FIG. 151, then lower to
(FIG. 141); Housing 201 supported by Switch
elevation in FIG. 148
206, Switch 206 supported by Platform 202
c. Raise Housing 201 to elevation in
Three
(FIG. 141)
FIG. 151+, less than elevation in FIG.
153+
d. Raise Housing 201 to elevation in
Four
FIG. 153+
Three
d. Raise Housing 201 to elevation in
Four
Switch 206 in or will return to second energy
FIG. 153+
well (FIG. 152); Housing 201 supported by
f. Lower Housing 201 to elevation in
One
external force; Switch 206 supported by Housing
FIGS. 160 or 166
201 and/or Platform 202; Platform 202 supported
by external surface
Four
f. Lower Housing 201 to elevation in
One
Switch 206 in or will return to second energy
FIGS. 160 or 166
well; (FIG. 152); Housing 201 supported by
external force; Switch 206 supported by Housing
201; Platform 202 supported by Switch 206;
FIG. 154
[0049] States Three and Four in the foregoing require an external force to support the Housing (such as a human, a fork lift, a crane, or similar). When the external force is removed following the event, then States Three and Four return to State One. If events which do not pass a point-of-no-return are removed, then the table of states and events is reduced to the following:
[0000]
TABLE FOUR
State
Event
Next State
One
b.
Two
One
c.
One
One
d.
One
Two
c.
One
Two
d.
One
[0050] In the foregoing, when the machine is in State One, one event, Event b, can transition the machine to State Two. In the foregoing, when the machine is in State Two, two events, Event c and d, can transition the machine to State One. Events b, c, and d are points of no return.
[0051] FIGS. 220 to 230 illustrate a Third Embodiment 300 of a kinematic state machine. In the Third Embodiment 300 , the kinematic pairing between the first and second bodies imposes five constraints on the degrees of freedom in relative movement between the bodies. In the Third Embodiment 300 , the kinematic pairing is prismatic.
[0052] Within this set, FIG. 220 illustrates a side elevation view of exploded components of the Third Embodiment 300 . FIG. 221 illustrates a top orthogonal wire frame view of the exploded components of the Third Embodiment 300 . FIG. 222 illustrates a section perspective view of the Third Embodiment 300 with the components assembled and in State One of the state machine.
[0053] FIGS. 223 to 230 illustrate elevation views of the Third Embodiment 300 , assembled, in which a first body, Housing 301 , translates vertically relative to a second body, Platform 302 . The Housing 301 and Platform 302 form a composite coordinate function which interacts with a Switch 303 ; vertical translation of the Housing 301 changes the composite coordination function via Cut-Out 305 (which is part of Housing 301 ), a Kicker 306 (which is part of Housing 301 ), and a Headboard 307 (which is part of Housing 301 ). Changes in the composite coordinate function interact with the Switch 303 at Switch-Finger 304 and trigger the events which change the states available to the state machine. The energy states of the Switch 303 (discussed in the table below) come from rotation of the Switch 303 about the lower interior corner; lines 309 and 310 on Switch 303 (see FIG. 223 ) illustrate the angle of the Switch 303 relative to a point of no return which occurs approximately when line 310 is just over vertical (see FIGS. 226 and 227 ). As described further below, these figures show the states and the triggering events of this embodiment of the kinematic state machine.
[0054] The composite coordinate function contacts the Switch 303 and imparts a force at a force vector on the Switch 303 in the ambient gravitational field or acceleration force. The shape of the Switch 303 , its density distribution (which is generally uniform in this example), and the space allowed between the Housing 301 and the Platform 302 determine that the Switch 303 may occupy two energy wells, separated by an energy barrier. The energy barrier occurs when the Switch 303 is tipped up on one corner, with line 310 oriented vertically. See, for example, FIGS. 226 and 227 . A first energy well occurs when the Switch 303 rests flat on its base upon the Platform 302 , which, due to the space allowed between the Housing 301 and the Platform 302 , occurs only when the Housing 301 is supported by the Switch 303 , which is supported by the Platform 302 , which is supported by the Accessory 308 . See, for example, FIGS. 224 and 225 . A second energy well occurs when the Switch 303 is tipped up on one corner, past the point of no return relative to the energy barrier, and the Cut-out 305 has not yet descended far enough to push the Switch 303 (via the Switch Finger 304 ) back over the energy barrier. See, for example, FIGS. 226 to 229 .
[0055] In all of these views, a force is transmitted to the Switch 303 from the Housing 301 ; the force has a magnitude, generated by the rate of the relative displacement of the Housing 301 and Platform 302 , and a force vector orthogonal to the slope of the combined coordination functions of the surfaces of the Housing 301 and Platform 302 where they contact the Switch 303 .
[0056] FIGS. 223 through 230 illustrate the following states and transitions:
[0000]
TABLE FIVE
State
Next
State narrative
Event
State
One
a. Raise Housing 301 below elevation
One
Housing 301 supported by external surface;
where Switch 303 falls from beneath
Switch 303 in intermediate energy level, between
Headboard 307 to the first energy well,
first energy well and energy barrier (FIGS. 223
then release
and 230)
b. Raise Housing 301 above elevation
Two
where Switch 303 falls from beneath
Headboard 307 to the first energy well,
then release
c. Raise Housing 301 to elevation where
Three
Kicker 306 pushes Switch 303 past
energy barrier, lower to where Cut-Out
305 pushes Switch 303 up to energy
barrier
d. Raise Housing 301 to limit
Four
Two
e. Raise Housing 301 to elevation less
Two
Switch 303 falls to bottom of first energy well,
than in FIG. 226, then lower to
Housing 301 supported by Switch 303, Switch
elevation in FIG. 224
303 supported by Platform 302 (FIG. 224)
c. Raise Housing 301 to elevation where
Three
Kicker 306 pushes Switch 303 past
energy barrier, lower to where Cut-Out
305 pushes Switch 303 up to energy
barrier
d. Raise Housing 301 to limit
Four
Three
d. Raise Housing 301 to limit
Four
Switch 303 in second energy well (FIGS. 226 to
f. Lower Housing 301 to contact external
One
229); Housing 301 supported by external force;
surface (FIGS. 223 and 230)
Switch 303 supported by Housing 301 and/or
Platform 302; Platform 302 supported by
external surface
Four
f. Lower Housing 301 to contact external
One
Switch 303 in second energy well (FIGS. 226 to
surface (FIGS. 223 and 230)
229); Housing 301 supported by external force;
Switch supported by Housing 301; Platform 302
supported by Switch; FIG. 226, no surface
beneath Accessory
[0057] States Three and Four in the foregoing require an external force to support the Housing 301 (such as a human, a fork lift, a crane, or similar). When the external force is removed following the event, then States Three and Four return to State One. If events which do not pass a point-of-no-return are removed, then the table of states and events is reduced to the following:
[0000]
TABLE SIX
State
Event
Next State
One
b.
Two
One
c.
One
One
d.
One
Two
c.
One
Two
d.
One
[0058] In the foregoing, when the machine is in State One, one event, Event b, can transition the machine to State Two. In the foregoing, when the machine is in State Two, two events, Event c and d, can transition the machine to State One. Events b, c, and d are points of no return.
[0059] FIGS. 178 to 217 illustrate elevation and top plan views of a Fourth Embodiment 400 . The top portion of FIGS. 178 to 217 illustrates a close elevation view; the bottom-left portion of FIGS. 178 to 217 illustrates an elevation view; the bottom-right portion of FIGS. 178 to 217 illustrates a top plan view. In the top plan view portion of these drawings, four switch seats are illustrated as part of the Housing 401 ; only two switch seats are illustrated in the elevation views. As with the other Embodiments, Housing 401 and Platform 402 are illustrated as single components. In an embodiment, these components may be formed from multiple plates, as illustrated with respect to the First Embodiment 100 . In the Fourth Embodiment 400 , the kinematic pairing between the first and second bodies imposes five constraints on the degrees of freedom in relative movement between the bodies. In the Fourth Embodiment 400 , the kinematic pairing is prismatic.
[0060] In the Fourth Embodiment 400 illustrated in FIGS. 178 to 217 , a first body, Housing 401 , may translate vertically relative to a second body, Platform 402 , which bodies form a composite coordinate function which interacts with a Switch 403 ; vertical translation of the Housing 401 changes the composite coordinate function, which, via the Switch 403 , triggers the events which change the states available to the state machine. As described further below, these figures show the states and the triggering events of this embodiment of the kinematic finite state machine.
[0061] In this embodiment, the Switch 403 may rotate about a central axis, when viewed in plan-view (from above). The Platform 402 in FIGS. 178 through 217 may occupy an opening within the Housing 401 . The composite coordinate function in contact with the Switch 403 is formed by Housing 401 and the top of the Platform 402 , which contact the Switch 403 . The composite coordinate function and the Switch 403 geometry define a set of energy wells, separated by energy barriers, discussed further below in relation to the states available to the finite state system. The energy wells in this Fourth Embodiment 400 are essentially identical, though a first set of the energy wells do not position the Switch 403 between the Housing 401 and the Platform 402 while a second set of the energy wells do position the Switch 403 between the Housing 401 and the Platform 402 . The energy barriers in this Fourth Embodiment 400 are found at the top of the peaks on top of the Platform 402 .
[0062] The composite coordinate function is configured to impart energy to the Switch 403 as the Housing 401 is raised, transitioning the Switch 403 from one energy well to the other, over the energy barriers. As the Switch 403 moves between the energy wells, the Switch 403 rotates about its central axis and is alternatively interposed or not interposed between the Housing 401 and the Platform 402 and the finite state machine transitions between states.
[0063] In all of these views, a force is transmitted to the Switch 403 from the Housing 401 ; the force has a magnitude, generated by the rate of the relative displacement of the Housing 401 and Platform 402 , and a force vector orthogonal to the slope of the combined coordination functions of the surfaces of the Housing 401 and Platform 402 where they contact the Switch 403 .
[0064] FIGS. 178 through 217 illustrate the following states and transitions of the Fourth Embodiment 400 :
[0000]
TABLE SEVEN
Next
State
Event
State
One
a. Raise Housing 401 below where
One
Housing 401 supported by external surface
Housing 401 lifts Switch Arm 404 above
(FIGS. 232 and 234)
teeth on Platform 402 (approx. FIG.
192)
b. Raise Housing 401 to where Housing
Two
401 lifts Switch Arm 404 above teeth on
Platform 402, and release (FIG. 193)
c. Raise Housing 401 above level of
Three
event b., but not to limit (FIG. 194, but
then raise the Housing 401 until before
the entire machine is lifted off of the
surface)
d. Raise Housing 401 to limit (FIG.
Three
194, but then continuing to raise the
Housing 401, until the entire machine is
lifted off of the surface)
Two
a. Raise Housing 401 below where
Two
Housing 401 supported by Switch 403, which is
Housing 401 lifts Switch Arm 404 above
supported by Platform 402
teeth on Platform 402 (approx. FIG.
192)
b. Raise Housing 401 to where Housing
One
401 lifts Switch Arm 404 above teeth on
Platform 402, and release (FIG. 193)
c. Raise Housing 401 above level of
Four
event b., but not to limit (FIG. 194, but
then raise the Housing 401 until before
the entire machine is lifted off of the
surface)
d. Raise Housing 401 to limit (FIG.
Four
194, but then continuing to raise the
Housing 401, until the entire machine is
lifted off of the surface)
Three
d. Raise Housing 401 to limit (FIG.
Three
Housing 401 supported by external force;
194, but then continuing to raise the
Housing 401 supports Switch 403; next State
Housing 401, until the entire machine is
when Housing 401 is lowered will be Two
lifted off of the surface)
f. Lower Housing 401 to contact external
Two
surface (FIGS. 232 and 234)
Four
d. Raise Housing 401 to limit
Four
Housing 401 supported by external force;
f. Lower Housing to contact external
One
Housing 401 supports Switch 403; next State
surface (FIGS. 178 and 217)
when Housing 401 is lowered will be One
[0065] States Three and Four in the foregoing require an external force to support the Housing (such as a human, a fork lift, a crane, or similar). When the external force is removed following the event, then State Three transitions to State Two and State Four transitions to State One. If events which do not pass a point-of-no-return are removed, and if transitional States Three and Four reflect their ultimate state, after the external lifting force is removed, then the table of states and events is reduced to the following:
[0000]
TABLE EIGHT
State
Event
Next State
One
b.
Two
One
c.
Two
One
d.
Two
Two
b.
One
Two
c.
One
Two
d.
One
[0066] In the foregoing, when the machine is in State One, three events, Event b, c, and d, can transition the machine to State Two. In the foregoing, when the machine is in State Two, three events, Event b, c, and d, can transition the machine to State One. Events b, c, and d are points of no return.
[0067] FIGS. 218 to 260 illustrate a Fifth Embodiment 500 of a kinematic finite state machine, in which the first and second bodies are connected at an axle, in which there are two Switches, 510 and 511 , neither of which has a single round vertical cross section, and show the states and events of this embodiment of the finite state machine as the first body moves.
[0068] In FIG. 218 , plates 501 - 505 illustrate Housing components. Elements 516 and 517 illustrate assembly of these Plates into Housing 516 and 517 ; note: the stacking order of Plates in Housing 516 is not the same as the stacking order of Plates in Housing 517 . A side elevation of both Housings is illustrated in box 514 (not including the Switches and omitting Housing Plate 501 ).
[0069] In FIG. 218 , plates 506 - 509 illustrate Platform components. A side elevation of both Platforms (and an accessory) is illustrated in box 513 . Box 515 illustrates a side elevation of both Platforms and Housings, assembled around axle 512 .
[0070] In FIG. 218 , elements 510 and 511 are Switches.
[0071] Within FIGS. 218 to 260 , FIGS. 219 to 259 show the states and events of the Fifth Embodiment 500 of the finite state machine as the first body moves. In these Figures, box 530 shows a schematic view of interaction of Switch 510 with components of Housing and Platform. Box 530 is not separately labeled in FIGS. 219 to 259 , but can be seen in a consistent position within these Figures. In FIGS. 219 to 259 , element 531 is a portion of Housing Plate 503 ; element 532 is a portion of Platform Plate 507 ; element 533 is a portion of Platform Plate 506 ; element 534 is a portion of Housing Plate 501 ; element 535 is a portion of Housing Plate 505 ; element 536 is a portion of Housing Plate 502 ; element 537 is a portion of Platform Plate 507 ; element 538 is a portion of Platform Plate 508 ; and element 539 is a portion of Housing Plate 504 . Only portions of the Plates are illustrated to focus on the control surfaces which interact with the Switches and to illustrate that the size of the Plates is not significant, so long as the space occupied by the Switches is not impinged upon as the composite coordinate function formed by the Housing and Platform is executed by raising and lowering the Housing.
[0072] FIG. 260 illustrates the Housing 517 or Housing 518 of the Fifth Embodiment 500 embedded in a larger solid body, element 520 . Element 521 illustrates a solid body with an opening consistent with Housing 514 . Element 522 illustrates an elevation view of Housing 514 and Housing Plate 501 .
[0073] FIG. 261 illustrates variations on the Switch, generally a Switch similar to the one illustrated in Embodiment Two ( FIGS. 134 to 166 ). These variations show mechanisms to dampen or delay the events (and state transitions), such as, for example, a viscous fluid which can flow from one side of the Switch to the other through an adjustable needle valve, 701 , ball bearings able to translate back and forth within a tube, 702 , or a horizontal screw which can be adjusted to change the center of gravity of the switch, 703 . These variations are shown together, 704 , in an embodiment of a Switch similar to the Switch illustrated in the Second Embodiment 200 .
[0074] The finite state machines described herein may be summarized as follows: Each comprises two bodies and a switch. The two bodies may move separately with at least one degree of freedom and a defined range of motion therein. The bodies may be connected at an axle and/or the bodies may interlock, with an allowed range of motion prior to the interlock. One or both of the bodies may contact an external surface.
[0075] At least one, if not two, of the bodies may form a composite coordinate function in conjunction with the geometry of the switch. The composite coordinate function may comprise coordinate functions obtained from each separate body and/or from components within one body (such as from plates which together comprise one body). The coordinate functions illustrated in this paper are generally linear equations (straight lines with a slope), but may be non-linear. The composite coordinate function transmits a force at a force vector to the switch, which force vector counteracts the force vector experienced by the switch in the gravitational field or acceleration force. The composite coordinate function changes as one of the bodies moves relative to the other.
[0076] The switch has a geometric structure, a density distribution, and is subject to gravity (or another acceleration force). Because the geometric structure and density distribution of the switch are known, because the composite coordination function is known based on the then-current relative position of the two bodies, and if, when relevant, the preceding state of the finite state machine is known (the state of certain finite state machines depends on the prior state of the finite state machine), the position of the switch relative to the composite coordinate function is also known. The position of the switch relative to the two bodies determines the state of the finite state machine.
[0077] The finite state machine may have at least two states: A first state wherein a first body contacts and/or is supported by an exterior surface, without being supported by the switch; and a second state wherein the first body is supported by the switch, which switch is supported by the second body, which second body is supported by an accessory and/or by an exterior surface. The first state transitions to the second state when the first body is raised, the variable surface formed by the first and/or second body either i) provides a force and force vector which counteract the force and force vector experienced by the switch in the gravitational field and moves the switch past a point of no return and transitions the switch from a first energy well over an energy barrier into a second energy well (Embodiment 4), or ii) releases a force and force vector which were counteracting the force and force vector experienced by the switch in the gravitational field and allows the switch to fall into the second energy well (Embodiments 1 through 3) whereupon the first body may be lowered into the second state, wherein the first body is supported by the switch and the second body. The second state does not change if the state machine is released. The second state may transition to the first state when the first body is raised past the point of no return where the composite coordinate function formed by the first and/or second body contacts the switch and provides a force and force vector which moves the switch past a point of no return and transitions the switch from the second energy well over the energy barrier, and into i) the side of the first energy well (Embodiments 1 through 3), or ii) entirely into the first energy well (Embodiment 4), whereupon the first body may be lowered to the ground, and, in the case of Embodiments 1 through 3, the composite coordinate function contacts the switch and provides a force and force vector which moves the switch past a point of no return and transitions the switch from the first energy well over the energy barrier, and into a position intermediate between the second energy well and the energy barrier.
[0078] Third and fourth transitional states may result, but require that one of the bodies be supported by an external force.
[0079] The finite state machines in Embodiments 1 through 3 exhibit the following state/transitions:
[0000]
TABLE NINE
state # --> (transitioning to) state #,
state # --> state #, eliminating
showing all states
intermediate states
1 --> 2
1 --> 2
1 --> 3 or 4 (limit), then 3 or 4 -->
1 --> 1
(through, but not stopping in, 2) 1
2 --> 3 or 4, then 3 or 4 --> 1
2 --> 1
2--> 1
2 --> 1
[0080] The finite state machine in Embodiment 4 exhibit the following state/transitions:
[0000]
TABLE TEN
state # --> (transitioning to) state #,
state # --> state #, eliminating
showing all states
intermediate states
1 --> 2
1 --> 2
1 --> 3 or 4 (limit), then 3--> 2;
1 --> 2
2 --> 3 or 4, then 3 or 4 --> 1
2 --> 1
2 --> 1
2 --> 1
[0081] A larger object may comprise more than one finite state machine. For example, and without limitation, a table may comprise a finite state machine on each corner of the table; the Housing-component of the table may be lifted vertically, without a rotational component, triggering events for each of the finite state machines on each corner. If the finite state machines in this example are identical, then the events would occur at essentially the same time. For example, and without limitation, a table may comprise a finite state machine on each corner of the table; the Housing-component of the table may be rotated along an axis at the base of one side of the table, in which case the finite state machines at the opposite side of the table (assuming they are all identical) would experience events at essentially the same time. A single object may comprise multiple different finite state machines, such as, for example, four different state machines being attached to the four corners of a table. In this way, different states, events, and state sequences may occur at each of the four corners, depending on how the table is raised.
[0082] The first or second objects—or a larger object to which the first and/or second objects may be attached—may have any shape which is consistent with the allowed range of motion of the first and second objects and which does not impinge upon the area occupied by the switch due to the composite coordinate function.
[0083] The control surfaces of the first and second objects, discussed herein in terms of the composite coordinate function, have a frame of reference which is an axis through the center of gravity of the Switch, which axis is in a plane perpendicular to the gravitational field of the machine. The Housing has two frames of reference: i) an attachment, if any, to a larger solid body to which the Housing may be attached (such as a table) and/or to an external surface upon which the Housing may come to rest; and ii) an axis through the center of gravity of the Switch, which axis is in a plane perpendicular to the gravitational field of the machine. The Platform has three frames of reference: i) the Housing, as determined by the kinematic pair relationship between the Housing and the Platform; ii) the axis through the center of gravity of the Switch, which axis is in a plane perpendicular to the gravitational field of the machine; and iii) an attachment, if any, to an accessory to which the Platform may be attached (such as a wheel) and/or to an external surface upon which the Platform may rest. The Housing and Platform have at least one shared frame of reference in the axis through the center of gravity of the Switch.
[0084] The state machines disclosed herein may be programmable by a user. For example, if the state machine is composed of joined plates, the user may remove one or more plates and replace the removed plates with other plates which may, for example, allow the state machine to bear a heavier load, or which scale the size of the state machine in one or more dimensions. Additional or different plates may be utilized to increase or decrease the number of states which are available to the machine.
[0085] At least one of the bodies may be connected or attached to an accessory, such as, for example, a wheel, a foot, a scale, a sensor.
[0086] The states available to the machine may be understood of as information states, wherein the information in the machine is processed based on the then-current state and the then-current event, with the output of processing the information states being a next state of the kinematic machine.
[0087] In the Embodiments illustrated herein, a first rigid body is an active component with a 3-dimensional load bearing surface with a minimum length and which physically embodies a coordinate function or a set of coordinate functions. A second rigid body is a passive component with a 3-dimensional load bearing surface with a minimum length and which physically embodies a coordinate function or a set of coordinate functions. The active and passive components have an allowed (limited) range of motion relative to one another. The coordinate functions of the active and passive components—together, a composite coordinate function—intersect with the surface of a switch as the first body is moved relative to the second body within the allowed range of motion. The active and passive components share a frame of reference in an axis which passes through the horizontal center of gravity of the switch and a plane which is perpendicular to a gravitational field in which the components are present. The composite coordinate function translates and/or rotates the switch through a volume occupied by the switch. In certain positions or orientations, the engaged positions, the switch engages with both bodies to transfer a force from the first body to the second, which force is greater than the weight of the switch by itself. In other positions or orientations, the disengaged positions, the switch experiences reactive forces from the composite coordinate function, which reactive forces are no greater than those produced by the weight of the switch (the mass multiplied by the acceleration of the switch, with acceleration driven by movement of the active component or caused by the gravitational field). The engaged and disengaged states of the switch define at least a subset of the states available to the machine. The states are generally separated by energy barriers defined by the gravitational field in which the machine exists, the composite coordinate function, and the switch geometry and center of gravity. The states, the composite coordinate function, the switch geometry and center of gravity, and the allowed range of motion between the first and second bodies define the volume which the switch occupies and the shapes of load bearing surfaces of the first and second bodies.
[0088] The raising limit of a finite state machine may be defined by the axle and/or the allowed range of motion of the interlocking bodies. For example, to provide the raising limit, a first body may comprise a cable, “U” shaped bracket or similar which projects through an opening in the second body or around a surface of the second body, which cable or similar comprises a nut or similar physical object which cannot pass through the opening or around the surface of the second body and which thereby interlocks with the second body at the raising limit (beyond which there is no change in state for the state machine). | Disclosed is a cyclic mechanism for engaging or disengaging a switch with the stage of the cycle being determined by a height to which a first object is lifted relative to a second object. The mechanism has few moving parts, is inexpensive to manufacture, is reliable, can be incorporated into a wide range of devices or structures, and operates as an incident to raising or lowering a first object relative to a second. | 1 |
FIELD OF THE INVENTION
[0001] The present invention pertains to apparatus and methods for atraumatically retracting tissue. In particular, the present invention creates and maintains an opening through soft tissue.
BACKGROUND OF THE INVENTION
[0002] Surgery on the heart is one of the most commonly performed types of surgery that is done in hospitals across the U.S. Cardiac surgery can involve the correction of defects in the valves of the heart, defects to the veins or the arteries of the heart and defects such as aneurysms and thromboses that relate to the circulation of blood from the heart to the body. In the past, most cardiac surgery was performed as open-chest surgery, in which a primary median sternotomy was performed. That procedure involves vertical midline skin incision from just below the super sternal notch to a point one to three centimeters below the tip of the xiphoid. This is followed by scoring the sternum with a cautery, then dividing the sternum down the midline and spreading the sternal edges to expose the area of the heart in the thoracic cavity. This technique causes significant physical trauma to the patient and can require one week of hospital recovery time and up to eight weeks of convalescence. This can be very expensive in terms of hospital costs and disability, to say nothing of the pain to the patient.
[0003] Recently, attempts have been made to change such invasive surgery to minimize the trauma to the patient, to allow the patient to recover more rapidly and to minimize the cost involved in the process. New surgical techniques have been developed which are less invasive and traumatic than the standard open-chest surgery. This is generally referred to as minimally-invasive surgery. One of the key aspects of the minimally invasive techniques is the use of a trocar as an entry port for the surgical instruments. In general, minimally invasive surgery entails several steps: (1) at least one, and preferably at least two, intercostal incisions are made to provide an entry position for a trocar; (2) a trocar is inserted through the incision to provide an access channel to the region in which the surgery is to take place, e.g., the thoracic cavity; (3) a videoscope is provided through another access port to image the internal region (e.g., the heart) to be operated on; (4) an instrument is inserted through the trocar channel, and (5) the surgeon performs the indicated surgery using the instruments inserted through the access channel. Prior to steps (1)-(5), the patient may be prepared for surgery by placing him or her on a cardiopulmonary bypass (CPB) system and the appropriate anesthesia, then maintaining the CPB and anesthesia throughout the operation. See U.S. Pat. No. 5,452,733 to Sterman et al. issued Sep. 26, 1995 for a discussion of this technique.
[0004] While this procedure has the advantage of being less invasive or traumatic than performing a media, sternotomy, there are numerous disadvantages to using trocars to establish the entry ports for the instruments and viewscope. For example, the trocars are basically “screwed” into position through the intercostal incision. This traumatizes the local tissues and nerve cells surrounding the trocar.
[0005] Once in place, the trocar provides a narrow cylindrical channel having a relatively small circular cross-section. This minimizes the movement of the instrument relative to the longitudinal axis and requires specially-designed instruments for the surgeon to perform the desired operation (See, e.g., the Sterman patent U.S. Pat. No. 5,452,733). In addition, because of the limited movement, the surgeon often has to force the instrument into an angle that moves the trocar and further damages the surrounding tissue and nerves. The need to force the instrument causes the surgeon to lose sensitivity and tactile feedback, thus making the surgery more difficult. The surgical retractor of this invention is designed to reduce the trauma to the patient in providing access to the internal region, to reduce the trauma to the patient during surgery, to provide the surgeon with greater sensitivity and tactile feedback during surgery, and to allow the surgeon to use instruments of a more standard design in performing the non-invasive surgery.
[0006] Other less invasive surgical techniques include access to the region of the heart to be corrected by anterior mediastinotomy or a thoracotomy. In a mediastinotomy, an incision is made that is two to three inches in length of a parasternal nature on the left or the right of the patient's sternum according to the cardiac structure that needs the attention in the surgery. Either the third or the fourth costal cartilage is excised depending on the size of the heart. This provides a smaller area of surgical access to the heart that is generally less traumatic to the patient. A thoracotomy is generally begun with an incision in the fourth or fifth intercostal space, i.e. the space between ribs 4 and 5 or ribs 5 and 6. Once an incision is made, it is completed to lay open underlying area by spreading the ribs. A retractor is used to enlarge the space between the ribs.
[0007] At the present time, when either of these techniques is used, a retractor is used to keep the ribs and soft tissues apart and expose the area to be operated on to the surgeon who is then able to work in the surgical field to perform the operation.
[0008] Major disadvantages of these systems include their limited positioning, complexity, and trauma to the surrounding tissue. It has now been discovered that the shortcomings of the retractors that are known in the prior art can be overcome with a new design as set forth in the following description.
BRIEF SUMMARY OF THE INVENTION
[0009] In general, the present invention provides a surgical retractor to allow improved access through a surgical opening through the tissue of a patient. The retractor includes a flexible ring, a plurality of flexible straps connected to the flexible ring, and a connector for attaching the end of the flexible strap to a support surface, such as a patient's skin, a surgical drape and a piece of surgical equipment. The connector may take the form of an adhesive patch on the flexible strap. Alternately, the connector may be a patch of hook or loop material connected to a surface of each of said plurality of straps and a coordinating patch of hook or loop material connectable by adhesive to the support surface.
[0010] The diameter of the flexible ring of the surgical retractor may be adjustable. The adjustment of the ring may be achieved with a ratchet mechanism.
[0011] One embodiment of the ratchet mechanism is spring loaded and may including: a plurality of openings extending into said flexible ring; an arm having an end sized and configured to extend into said plurality of openings, said arm having an engaged position wherein said end of said arm is located within one of said plurality of openings and a released position wherein said end of said arm is outside all of said plurality of openings; and a spring configured to bias said arm towards said engaged position.
[0012] The flexible straps of the surgical retractor may be frangibly connected together. One version of the connection is created by a narrowed portion of the strap material. The straps and sleeve of the surgical retractor are formed of a soft, resilient material, such as silicone material.
[0013] The flexible straps of the surgical retractor may be constructed of a soft, resilient material, such as silicone, which provide an atraumatic barrier between the ribs and soft tissues adjacent to the incision site. This reduces the amount of trauma to the ribs and soft tissues caused by various surgical instruments (ie. rib spreaders, surgical tools, etc)
[0014] One embodiment of the surgical retractor includes a light source molded into said flexible ring. The light source may take the form of a plurality of LEDs.
[0015] In one embodiment, the flexible ring includes an inflatable bladder. A pneumatic line may be attached to said inflatable bladder.
[0016] An embodiment of the surgical retractor has a flexible ring that is approximately round.
[0017] One embodiment of the surgical retractor includes a malleable flange extending from a distal end thereof.
[0018] A method of using a surgical retractor in a surgical incision, includes the steps of: inserting a distal end of the surgical retractor into the surgical incision; causing a ring located on the distal end of the surgical retractor to open to a deployed configuration; placing a plurality of a first part of a coordinating fastener around the surgical incision; pulling a plurality of straps connected with the ring and having a second part of said coordinating fastener such that said second part of said coordinating fastener is connected with said first part of said coordinating fastener.
[0019] The method may also include the step of performing a surgical procedure through a passageway extending through the surgical retractor. The surgical procedure may include CABG, valve repair, valve replacement and/or ablation.
[0020] One surgical procedure using the surgical retractor is a cardiac ablation procedure. In the procedure two surgical retractors are used in two thoracic incisions located on an opposite side of the sternum.
[0021] A method including stretching the straps, thereby providing additional force against tissues forming an edge of the surgical incision.
[0022] An embodiment where the parts of the coordinating fastener are hook and loop fastener material and the straps of the surgical retractor are repositioned.
[0023] A method includes the step of inflating an inflatable bladder which forms the ring.
[0024] A method includes the step of bending outward a malleable flange extending from a distal end of the surgical retractor.
[0025] A further method is performed by pulling the straps different amounts to create a non-round passageway.
[0026] Yet a further method is performed by pulling the straps approximately the same amount to create a generally round passageway.
[0027] The present invention can be used to provide tissue retraction and expand access openings by means of the strength and elastic properties of the materials used to manufacture the retractor. The present invention is also configured to be couplable with an adjustable surgical retractor with blades to be inserted into the patient cavity for large expansion against opposing thoracic structures while providing atraumatic contact with those anatomical structures.
[0028] The present invention provides the ability to function to retract tissues, without significant expansion of the incision, but also to enlarge the size of the incision, a function that is provided by the tear strength of the silicone or the ability to combine it with an adjustable surgical blade.
[0029] The present invention provides the ability to adjust the tensioning of the straps even after initial deployment through the use of the hook and loop material. This may be necessary when a surgeon needs to enlarge the incision to gain better access to the surgical site. Competitive devices use an adhesive that does not allow for repositioning subsequent to initial deployment.
BRIEF DESCRIPTION OF THE DRAWINGS
[0030] FIG. 1 is a top perspective view of the atraumatic tissue retraction device.
[0031] FIG. 2A is a top perspective view of the atraumatic tissue retraction device in use.
[0032] FIG. 2B is a top perspective view of the atraumatic tissue retraction device with the straps extended farther outward.
[0033] FIG. 3 is a top perspective view of the atraumatic tissue retraction device with the straps extended asymetrically.
[0034] FIG. 4 is a side perspective view of the atraumatic tissue retraction device having an inflatable bladder.
[0035] FIG. 5 is a close up view of a ring diameter adjustment mechanism for the atraumatic tissue retraction device.
[0036] FIG. 6 is a close up view of lighting integrally molded into the base of the atraumatic tissue retraction device.
[0037] FIG. 7 is a side perspective view of the atraumatic tissue retraction device with flanges extending from the bottom ring.
DETAILED DESCRIPTION OF THE INVENTION
[0038] FIG. 1 is a top perspective view of the atraumatic tissue retraction device 10 . The atraumatic tissue retractor 10 is a device used to keep the field of view of a thoracotomy, sternotomy, or other surgical portal clear of soft tissues, as well as limit or prevent trauma to the ribs and other soft tissues. The device includes a sleeve 12 with an elastic or flexible ring 14 in the lower or distal end. The ring 14 may be formed of any resilient or elastic material, such as Nitinol, other metals, and plastics. The ring 14 may be adhered, bonded, overmolded into or otherwise connected to the base of the sleeve 12 . The sleeve 12 is divided into a multiplicity of straps 16 . Any suitable number of straps 16 may be used, preferably from three to twenty, more preferably in the range of four to fourteen and most preferably from six to ten. In the embodiment shown, eight straps 16 are used. Any soft resilient, flexible material may be used to form the sleeve. One suitable material is silicone. Other possible materials include, but are not limited to low durometer polyurethane, nitrile, natural rubber, or low durometer polyvinylchloride.
[0039] A piece of hook or loop material 18 is adhesively bonded or otherwise attached to each strap 16 . Included with the device 10 is the coordinating piece of hook or loop material 20 with an adhesive back, as seen in FIGS. 2A , 2 B and 3 . In the embodiment shown, a set of eight hook pads 18 are adhesively bonded to the straps 16 and eight mating loop pads 20 are attached to the user, the drape or another nearby stable support structure in the surgical field. In the embodiment shown, the straps 16 include holes 22 at the proximal end to allow the user to easily grip the strap 16 and/or hook the strap 16 with an instrument or to a nearby structure.
[0040] To use the device 10 , the user peels the backing off of the loop pad 20 , thereby exposing an adhesive and places it onto the patient's chest, other tissue, surgical drape or other nearly support adjacent to the incision as seen in FIG. 2 . The ring 14 of the retractor 10 is then folded or deformed and pushed into the incision. When inserted into the incision, the ring 14 springs back to shape and anchors the distal end of the retractor 10 . The eight straps 16 are then pulled away from the incision and adhered to the loop pads 20 via the hook pads 18 to retract the soft tissues. In this manner, the retractor 10 has created and/or maintains an opening and passageway to the surgical site. The distal portion of the straps 16 or the sleeve 12 portion above the ring 14 also protect the tissue from the surgical instruments as they are passed into and out of the passageway.
[0041] The present invention is particularly suited for thoracic surgery. In cardiac surgical procedures, the surgical retractor 10 is inserted into at least one incision into the chest to provide access for a surgical procedure, such as CABG, valve repair/replacement and/or ablation procedures. A preferred method is for use in cardiac ablation procedures with one retractor 10 in each one of two thoracic incisions on opposite sides of the sternum. The straps 16 being formed of silicone allow the retractor 10 to provide positive traction to the surrounding tissue and to atraumatically contact and retract the thoracic structures and nerves during any of these procedures.
[0042] In use, the surgical retractor 10 has several advantages over typical retractors. The retractor 10 is able to retract tissues, without significant expansion of the incision or to enlarge the size of the incision, if needed. This function is created by the tear strength of the silicone. The versatility of the device 10 is further increased through the use of the hook and loop material. This fastening approach allows for adjustment and re-tensioning of the straps during the procedure.
[0043] For ease of use, the straps 16 may be connected along their edges 24 to create the elongated, sleeve 12 structure for initial deployment. The connection 26 between the straps 16 may be formed of a frangible connection 26 that the user may pull apart if desired. In the embodiments shown, the frangible connection 26 is created by molding a narrowed or necked down portion of the strap 16 material. Prior to or during use, the user can easily tear along this weakened portion 26 to separate the strap 16 along as much of the length as desired. FIGS. 2A and 2B show the same embodiment of the retractor 10 in place in a patient in two different configuration. In FIG. 2A , a majority of the length of the straps 16 remains connected along the sides 24 . This creates a fairly deep opening for situations where the retractor 10 needs to hold back tissue extending a longer distance into the patient. In FIG. 2B , the straps 16 are pulled out further and separated along most of their lengths. In this version, the retractor 10 is only being used to hold open a comparatively shallow opening. FIG. 7 shows a version of the straps 16 where the straps 16 are connected at the base and at a discrete point 80 near the proximal end of the straps.
[0044] Depending on the resilience of the tissue being retracted, the straps 16 may be merely pulled taught and attached to the loop pads 20 as seen in FIG. 2A . Or if additional force is required, the straps 16 may be pulled and stretched, such that the resilience of the straps 16 provides additional retraction force to open and hold open the tissue surrounding the retractor 10 , as seen in FIG. 2B . The straps 16 may be overlapped to assure that the tissue being retracted is completely covered by the straps. To accomplish this, the straps 16 may widen as they extend upward from the ring 14 .
[0045] If desired, only some of the strap may be separated, as seen in FIG. 3 . In this embodiment, a thin section near the proximal end of the device is used to connect the straps together. The user then only breaks the frangible connection between the straps for a desired number of straps. In the embodiment shown, a group of two and a group of three straps are left attached together.
[0046] Using different tension on the different straps 16 may also allow the user to create a different shaped openings. Such as, stronger tension on two or four (two pair of side-by-side) opposing straps 16 could be used to create an oval or oblong opening. Other effects may be created by varying the relative widths and/or direction of pull of the straps 16 . The hook 18 and loop 20 connection also allows the user to independently position, adjust and/or reposition the straps 16 and therefore the retractor 10 during use. If desired, the hook 18 and loop 20 material may also be used as suture stays.
[0047] Since the loop pads 20 may be selectively placed as needed, a single size of retractor 10 may be suitable for use for a wide range of size of patient. Further range may be provided by creating additional retractor units 10 of different sizes, including length of straps 16 , thickness of straps 16 , width of straps 16 , diameter of distal ring 14 , etc.
[0048] In FIG. 4 , the flexible ring 14 at the base of the sleeve 12 is formed of or includes an inflatable bladder 30 . A pneumatic line 32 is connected to a source of inflation medium, such as saline or other fluid or gas. The inflation medium source may be in the form of a syringe or a pump that injects the inflation medium into the inflatable bladder 30 and thereby holds the retractor 10 in place. Preferably the system has a mechanism, such as a stopcock or other standard sealing mechanism, to temporarily seal the proximal end of the pneumatic line 32 to maintain the inflation of the bladder 30 , while the retractor 10 is in use. Once the procedure is complete, the user can unseal the system and withdraw the inflation medium through the pneumatic line 32 .
[0049] If desired, the ring may be adjustable. The adjustability of the ring may be created in any suitable manner. FIG. 5 shows an embodiment of the retractor 40 that uses a ratchet type mechanism 44 to allow the user to expand the ring 42 once the ring 42 is in place. In this embodiment, the retractor 40 would be supplied to the user in a collapsed state and expanded once inserted into the chest cavity to anchor the retractor 40 . The expansion would occur by the user mechanically increasing the diameter of the opening and ring 42 by hand or with one or more instruments. A spring-loaded locking lever 46 would be biased toward the ring 42 surface and holes 48 extending into or through the ring 42 . The configuration of the locking lever 46 would allow the lever 46 to easily rise out of the holes 48 while the ring 42 is being expanded, but would be held securely in place inhibiting the ring 42 from collapsing. For the purposes of releasing the ring 42 to remove the retractor 40 after surgery, the spring 50 that biases the lever 46 toward the holes 48 would be compressed to allow the end of the lever 46 to pull out of the hole 48 , and thereby allowing the ring 42 to collapse. Alternately, a shape memory alloy could be used. The function of this alloy would be to hold the ring in its expanded state when at room temperature, and then to release the ring when it's temperature is elevated. Alternately, a component that is able to be severed by an electrosurgery probe or other surgical instrument could be used to hold the ring in its expanded state. In this case, the support component would be severed to allow the ring to collapse.
[0050] Alternate versions of the adjustable ring also may be used. One version could use a mechanical stop that is actuated by hydraulic means to hold the ring in its expanded state. A piston could be actuated by hydraulic or mechanical mechanisms. Or a threaded member could be twisted to expand or contract the ring.
[0051] Additionally, the distal end of the device 60 can be outfitted with a light source 62 for the purposes of illuminating the surgical site. The light 62 may take the form of an accessory that is attachable to the retractor or it may be integrally formed with the retractor 60 . FIG. 6 shows a retractor 60 having a series of batteries 64 molded into silicone in one or more of the straps 16 . A series of LED's 66 are also molded into the silicone around the distal ring 14 . Leads 68 connect the LED's 66 and batteries 64 to a switch 70 , such as a push button contact switch or other suitable switch, which allows the user to turn the light source 62 on and off.
[0052] Another embodiment of the retractor 78 has an inflatable, adjustable or malleable flange extending from the bottom of the ring, as seen in FIG. 7 . Initially, the malleable flange 82 would extend down from the ring 14 . Once the retractor 78 has been lowered into place, the flange 82 could be bent outward to help anchor the retractor 78 in place. The flange 82 could be bent only slightly or it may be bent such that it is fully perpendicular or further. The flange 82 may be bent to conform to the shape of the chest wall, ribs or other structure. Stainless steel is a suitable material, although any biocompatible or coated malleable material maybe used. This embodiment of the retractor 78 also shows adhesive patches 84 used to connect the straps 16 directly to the support surface. The adhesive patches 84 have a disposable peel off backing 86 to protect the adhesive prior to use.
[0053] The retractor may be supplied as a sterile, single use device or a reusable device formed of materials suitable for sterilization procedures.
[0054] Many features have been listed with particular configurations, options, and embodiments. Any one or more of the features described may be added to or combined with any of the other embodiments or other standard devices to create alternate combinations and embodiments.
[0055] Although the invention has been fully described above, in relation to various exemplary embodiments, various additions or other changes may be made to the described embodiments without departing from the scope of the present invention. Thus, the foregoing description has been provided for exemplary purposes only and should not be interpreted to limit the scope of the invention as set forth in the following claims. | Methods and apparatus for a surgical retractor include a ring, a plurality of flexible straps connected to the ring, a patch of hook or loop material connected to each strap, a coordinating patch of hook or loop material connectable to the patient's skin or the surgical drape. The flexible straps of the surgical retractor may be frangibly connected together. LEDs molded into the distal end create a light source to illuminate the surgical site. The ring may take several forms including a flexible or adjustable ring and an inflatable bladder. The ring of the surgical retractor is inserted into the surgical incision, a patch of loop fastener is attached to the patient, a set of straps connected to the ring are pulled outward and the hook portion is applied to the loop portion to hold the incision open. The retractor is useable for thoracic and other types of surgery. | 0 |
This application is a continuation of continuation application Ser. No. 08/341,852, filed Nov. 18, 1994 now abandoned, which is a continuation of application Ser. No. 08/111,691, filed Aug. 25, 1993 now abandoned.
BACKGROUND OF THE INVENTION
This invention relates to pivoting tables, and particularly to tables having power tools mounted thereon, such as a saw of the type which is mounted on a first side of a table for movement between two dispositions so that in a first disposition, the saw is above the first side of the table and can be manipulated to work on workpieces supported on said first side, and in a second disposition, the saw is below the first side of the table, a blade thereof projecting through a slot in the table to work on workpieces supported on a second side of the table.
Such an arrangement was first described in DE-A-1628992. Here a saw is mounted on a table which is pivoted in a frame and flips over between two modes of operation; a first snip-off mode and a second bench saw mode.
One of the benefits of such an arrangement is its versatility. Not only does it flip between two, quite different, modes of operation, but also it is mounted on a frame and arranged so that it is transportable.
However, a table which is capable of flipping over has numerous other uses, and it is an object of the present invention to provide a table having a novel method of attachment to its frame enabling easy and convenient flip over so that either surfaces of the table can be arranged upper most in the frame.
SUMMARY OF THE INVENTION
In accordance with this invention there is provided a pivoting table comprising a table and a frame, the table being pivoted about a first axis to an intermediate member which is pivoted about a second parallel axis to the frame, means being provided to rotate said table about said first axis when the member is pivoted about said second axis.
Preferably said first axis moves from a position above the level of the table to a position below the level of the table.
The table may have a first wheel fixed thereto around said first axis and said means rotates the wheel when the member pivots about the second axis.
Said means may comprise a belt around said first wheel and around a second wheel fixed around said second axis, so that pivoting of said intermediate member relative to the frame rolls the first wheel inside the belt and rotates the table.
Preferably, the first and second wheels are dimensioned so that, given the extent of the pivot of said intermediate member relative to the frame, the first wheel and table rotate through 180° between two dispositions thereof.
Said first wheel may be mounted on one side of the table, in which case said wheels and intermediate member are arranged so that the two sides of the table are at the same level in the game in the two dispositions of the table.
The table preferably includes catch means to lock the table in either disposition. Preferably the frame has a catch member at both ends of the frame adapted to catch and support the front edge of the table in either of its dispositions.
Needless to say, it is extremely preferable to have two of said pivot systems, one on either side of the table and frame.
Such a table finds particular application in a power tool such as a saw of the type disclosed in DE-A-1628992. Nevertheless, a table which flips over in this manner doubtless has other applications as well which might also benefit frown the arrangement defined above.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention is further described hereinafter, by way of one example only, with reference to the accompanying drawings, in which:
FIG. 1 is a front view of a saw mounted on a table according to the present invention;
FIG. 2 is a side view (transparent) of the saw of FIG. 1 in a bench mode of operation;
FIG. 3 is a side view, partly cut away, of the saw of FIGS. 1 and 2 in the snip-off position; and,
FIG. 4 is a sequence of side views (transparent) showing flip-over from snip-off to bench saw modes.
FIG. 5 is a side view of the frame of a preferred embodiment of the present invention; and,
FIG. 6 is a front view, partly in section along the line VI--VI in FIG. 5 of the embodiment shown in FIG. 5.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
In FIG. 1, a power tool 10 is a saw and has legs 12 supporting a frame 14. A table 16 is pivoted with respect to the frame through a pivot system 18 described further below. On the table 16, on a first side 16a thereof, is mounted a saw assembly 20.
The saw assembly 20 comprises a pivot 22 (see also FIG. 3) between a pivot member 24 and a saw housing 26. A spring 28 biases the saw housing 26 to an open position as shown in FIG. 3.
The saw housing 26 includes a motor 30 drivingly connected to a saw blade 32 (see FIG. 2) under a lower guard 34. A handle 36 is operable to pivot the housing 26 up and down about pivot 22 to plunge the blade 32 into workpieces supposed on the side 16a of the table 16. A fence 17 is used to position workpieces. The table 16 has a slot (not visible) into which the blade can be lowered.
When pivoted right down against the table 16, the housing 26 can be locked in position by means not shown. When locked in this position, as shown in drawing A of FIG. 4, the table 16 is ready for pivoting to the bench saw mode shown in FIG. 2. Here, the second side 16b is uppermost and the blade 32 protrudes right through the table 16. This mode is particularly useful for rip cutting of long workpieces moved relative to the blade over, but supported on the table 16.
The pivoting system 18 allowing flip over between the two modes of operation shown in FIGS. 2 and 3 comprises a first toothed wheel 40 which is fixed to the side 16a of the table through a bracket 42 secured to the table by bolts 44 (see FIG. 1). Two such wheels 40 and brackets 42 are provided, at either edge of the table on the side 16a, but only one is shown in the drawings.
A second wheel 50 is fixed in each side 13 of the frame 14. An intermediate member 46 is pivoted about the centre of each wheel 40,50 and serves to tension a belt 48 around the two wheels. A cover 52 extends over the wheels 40,50.
As the member 46 pivots around the axis or axle 51 of the wheel 50, the wheel 40 is forced to roll inside the belt 48. Since the table 16 is rigidly connected to the wheel 40, the table pivots about pivot axis or axle 41, being the axis of the wheel 40 in the member 46. Moreover the axis moves transversely with respect to itself between two positions indicated at 41a and 41b in the drawings.
The dimensions and positions of the wheels 40 and 50, and the length of the member 46, are so arranged that, on pivoting through an angle x (which is sufficient to take the pivot axis or axle 41 as far below (t"), the centre line between sides 16a and 16b of the table as it presently is above (t') that line in FIG. 3, i.e.. t'=t") while at the same time completing half a revolution of the wheel 40 and thus mining the table 16 upside down.
This sequence of moves is shown in FIG. 4. In drawing A, the table has side 16a uppermost and the saw assembly 20 is in the snip-off mode, although the saw housing 26 is locked in its lowered position with the blade 32 protruding through the table. Here axis 41 is in its first position 41a. In drawing B, the front 16c of table 16 has been pulled forwardly and lifted. By virtue of the pivot system 18, the table cannot lift without coming forward and cannot come forward without lifting. In other words, the table is constrained to follow just the single path or sequence of moves illustrated. In drawing C, the table is vertical having been rotated through 90°. The intermediate member 46 has already passed its peak in this position so that no further lifting of the table and assembly is necessary.
In drawing D, the saw assembly 20 is beginning to enter the frame 14 and in drawing E it is inside the frame with the table 16 completely inverted (i.e. with side 16b now uppermost). Here axis 41 has moved completely to its second position 41b. Moreover, the second side 16b of the table is at the same level with respect to the frame 14 as the first side 16a was in the snip-off mode of drawing A. Thus accessories connectable to the frame 14 can be arranged to be useful to both modes of operation of the saw without having to arrange for any change of height of the table.
Mowerover, the axis or axle 41 moves in an arc 41c between its two positions 41a, 41b and from either position the axis or axle 41 first moves upwardly so that the table is always raised against gravity from either disposition.
Referring back to FIG. 3, the rear end 16d of the table 16 is unsupported. A rear knob 60 having a hook 64 is rotatably mounted in the side of the frame 14 on a bolt 62, but it has no function in this position of the saw. However, a stop block 66a is fixed in the side 13 of the frame 14. The intermediate member 46 abuts the block 66a and through the connection of the member 46 to the back of the table 16, supports the table at its rear edge 16d.
Knob 60 is connected to a front knob 70 by a cable 71. Instead of a bolt 62, knob 70 has a handle 72 by means of which it may be turned. Otherwise it is structurally the same as knob 60 and is rotably mounted in the side of the frame 14. It has a hook 74 which catches a catch ledge 76 on the table 16 and which has catch surfaces 76a and b. In the snip-off mode, it is catch 76a which is captured by the hook 74. Rotation of the handle 72 releases hook 74 from the catch. Moreover, the front of the table is supported by the ledge 76 resting on the knob 70. Only one catch is necessary to hold the table 16 down, because the rear edge 16d, for example, cannot rise without the front edge 16c rising. In other words, since the front edge 16c is locked by hook 74, then the whole table is locked as well. In any event, the table is heavy at its rear edge with its burden of the saw assembly 20, and so it is unlikely to lift anyway.
On release of the hooks 74, (there being one on each side of the frame) the table can pivot as described above with reference to FIG. 4. However, when the table again comes to rest in its inverted disposition on the knobs 60,70, it is hook 64 of the knob 60 which engages catch surface 76b of catch 76. Moreover, it rests on knob 60 and so supports the front (now rear) edge 16c of the table. Again, the rear edge 16d (now at the front) is unsupported except that a second stop block 66b is formed in the side 13 of the frame 14 and against which the member 46 abuts in the bench mode position. Again, no catch is required here because end 16d of the table cannot lift in the bench mode position without edge 16c lifting simultaneously, and again to a much greater extent. Moreover, the weight of the saw housing holds that end down. Preferably both knobs 60,70 are spring biased in an anti-clockwise direction (looking at FIG. 3) although only knob 60 absolutely requires it given the cable 71 arrangement shown.
One of the major benefits of this arrangement is that the table 16 is constrained to a single freedom of movement, despite the somewhat complicated nature of that movement. But, as a consequence of this constraint, there is little risk of the arrangement jamming as it might if, for example, the crudest form of the present invention as defined above was employed. In that case it would be essential for the operator to ensure that the table remained square to the frame, or that he pivoted the table at the right moment in relation to the transverse movement of the pivot axis. However, with the present arrangement no such care is required. Pulling the table forward has the effect of commencing pivoting of the table, and vice versa. Thus while cruder forms of the present invention are feasible, the arrangement described with reference to the drawings is preferred.
Finally, although FIGS. 1 and 3 show the intermediate member 46 to one side of the wheels 40,50 an alternative arrangement is shown in FIGS. 5 and 6. Here, the wheels 40,50 are each constructed from two half-shells 40a,b and 50a,b, with the member 46 disposed between the half-shells. This has the effect of reducing bending loads on the member 46, because it is supported by the wheels, at least at its most vulnerable areas near its pivots or axle 41,51 to the wheels 40,50 respectively.
FIG. 5 also shows an adjustment mechanism 80 to tension the belt 48 which comprises a tensioner 82 having a curved surface 84 pressing the belt 48 and being connected to the member 46 by bolt and nut 86. The bolt passes through an eye 88 of the tensioner enabling its adjustment. | A table (16) is pivotable about an axis (41) with respect to a frame (14) between two working dispositions. A power tool working assembly (20) may be mounted on the table. A working head (eg blade 32) of the assembly (20) is positionable through an aperture in the table so that it can work on workpieces supported above either side of the table.
The table is connected to the frame through an intermediate member (46) which is pivoted to the frame. The table has a first wheel (40) fixed thereto and a belt passes around the first wheel and around a second wheel (50) fixed to the frame (14) around the pivot (51) of the intermediate member. Pivoting of the intermediate member relative to the frame rolls the first wheel inside the belt and rotates the table between bench mode (FIG. 2) and snip-off mode (FIG. 3). | 1 |
CROSS REFERENCE TO RELATED APPLICATIONS
This is a continuation-in-part application of pending U.S. Ser. No. 08/223,768 of Christopher L. Allgeier, Sr. and Ryan M. Sell for "Method of Refilling Ink Jet Printer Cartridges" filed Apr. 4, 1994. The details of that application are incorporated herein by reference.
BACKGROUND OF THE INVENTION
This invention pertains to the art of printer cartridges, and more particularly to ink-jet printer cartridges such as a high capacity print cartridge sold as the Hewlett Packard® DeskJet/DeskWriter® 51626A High Capacity Print Cartridge. The invention is particularly applicable to a method of refilling an empty ink-jet printer cartridge of this type and will be described with particular reference thereto. It will be appreciated, however, that details of this invention may be advantageously employed in related environments and with other commercially available printer cartridges.
Ink-jet printer technology typically employs a cartridge or housing that carries a quantity of ink in an internal chamber or cavity that is formed into droplets for dispensing through a nozzle and onto a printing medium such as paper. For example, ink droplets are formed in response to an electrical signal that heats the ink and creates an ink vapor bubble that pushes ink out of the nozzle. An electrical resistive element heats the ink in an extremely rapid fashion so that it can be dispensed in a matter of milliseconds. Still other structures can be used to dispense ink droplets onto paper, the details of these ink-jet printer technologies being well known in the art. Since the structure and operation of printer cartridges of this type are well known in the art, further discussion herein is deemed unnecessary.
Ink-jet printer cartridges of this type are sold as original equipment and not promoted for reuse. It is generally recognized, however, that the costs associated with a new printer cartridge need not be encountered since additional savings can result from refilling an empty printer cartridge. In fact, it is believed that a substantial savings can result for the consumer when a single printer cartridge is refilled a number of times.
The above-identified parent application particularly teaches a preferred arrangement and method for refilling an empty printer cartridge. Likewise, U.S. Pat. No. 5,329,294 describes another arrangement and method for refilling an empty cartridge. The teachings of that patent are also incorporated herein by reference.
Known arrangements suffer from various problems, some of which are addressed by the above-noted application. For example, ink may be wasted or leak from the printer cartridge during the refill process. Suppliers of refill kits recognize this problem and suggest that the consumer use special containers or absorbent pads during the refill procedure to capture overrun ink. Still another problem is the chance that a user will not properly follow instructions provided with the refill kit. This can result in improper introduction of ink into the cartridge, some of which may be spilled or unnecessarily expelled from the printer cartridge. Other users may improperly prime the refilled printer cartridge.
Accordingly, a system and assembly that eliminates, or at least substantially curtails, common errors encountered during the refill process are required. Thus, it is desired to provide a new system that overcomes these and other problems in a reliable, easy to use manner that eliminates the potential for problems to develop.
SUMMARY OF THE INVENTION
The present invention contemplates a new and improved refill assembly and system that overcomes the above-referenced problems and others and provides an inexpensive and accurate apparatus and method for refilling printer cartridges.
According to the present invention, the assembly includes a base member that is adapted to receive a printer cartridge. A lid is received on the base and has separate stations that perform independent operations of the refill process.
According to a more limited aspect of the invention, the lid forms a seal with the printer cartridge so that air flow to an internal chamber of the printer cartridge is controlled during the refill process.
According to yet another aspect of the invention, the assembly refills the cartridge to the same capacity as the original equipment manufacturer and ultimately seals the cartridge once the refill process is complete.
According to yet another aspect of the invention, a predetermined quantity of air is introduced into the cartridge.
A primary advantage of the invention resides in a semi-automated refilling procedure for a printer cartridge.
Yet another advantage of the present invention is found in the elimination of errors associated with the refilling process.
Still another advantage of the invention is realized by the accurate refill of ink to the printer cartridge in a manner that contains any spills, mess, or the like.
Still other advantages and benefits of the invention will become apparent to those skilled in the art upon a reading and understanding of the following detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention may take physical form in certain parts and arrangements of parts, a preferred assembly or refill system and method of which will be described in detail in this specification and illustrated in the accompanying drawings which form a part hereof, and wherein:
FIG. 1 is an exploded view of the individual components that comprise the subject new assembly;
FIG. 2 is a perspective view of the base of the new assembly;
FIG. 3 is a longitudinal cross section of the base of FIG. 2 taken generally along the lines 3--3 thereof;
FIG. 4 is a perspective view of the subject new assembly with the first station positioned in a operative location;
FIG. 5 is a perspective view similar to FIG. 4 showing the third station in an operative location and receiving an ink refill tank;
FIG. 6 is another perspective view similar to FIG. 4 with the fourth station shown in operative location;
FIG. 7 is a top perspective view of the rotatable disk of the lid which illustrates the separate stations received thereon;
FIG. 8 is a perspective view of the underside of the rotatable disk;
FIG. 9 is a perspective view of the third station with selected components removed for ease of illustration;
FIG. 10 is a view of the underside of FIG. 9;
FIG. 11 is a longitudinal cross-sectional view of the third station taken generally along the lines 11--11 of FIG. 9;
FIG. 12 is a top plan view of a portion of the fourth station with selected components removed for ease of illustration;
FIG. 13 is a perspective view of selected components of the fourth station; and,
FIG. 14 is an elevational view of other selected components of the fourth station.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to the drawings wherein the showings are for the purposes of illustrating the preferred embodiment of the invention only and not for purposes of limiting same, the FIGURES show a refill assembly A having a base B and a lid C that includes a rotatable disk D having separate work stations for undertaking individual steps in refilling a printer cartridge E.
More particularly, and with reference to FIG. 1, the base B is preferably of molded plastic construction and has a generally cylindrical or tapered cylindrical configuration with a pair of side bosses 20, 22. The bosses extend from a first or closed end 24 of the base to a second or open end 26. Accordingly, the base defines a cup-shaped container having an internal cavity 28 adapted to receive a used or empty printer cartridge E.
The open end of the base is adapted to receive the disk D. The disk has a generally circular outer wall 32 and a generally planar platform 34. Individual stations are mounted on the upper surface of the platform and will be described in greater detail below. However, it should be understood that each station performs an individual step in the refill process and by selectively rotating the disk relative to the base in which the printer cartridge is mounted, the individual steps of the refill process may be performed on the printer cartridge.
Received over the disk is a cap 38 which has a latching assembly defined by a pair of downwardly extending legs 40, 42. Each leg includes a raised area 44 that cooperates with an opening 46 in the bosses 20, 22 of the base to provide a snap-fit latching connection of the lid (i.e., the cap and disk) to the base. The legs have some flexibility so that they can be deformed inwardly toward one another for receipt in slots 48 defined in the second end 26 of the base. Upon continued axial insertion of the lid C, the resilient character of these legs urge the raised portions 44 outwardly through openings 46 to lock the lid, disk, and base together. It will be understood, however, that the disk can still rotate relative to the base when the cap 38 is mounted on the base.
With continued reference to FIG. 1, and additional reference to FIGS. 2 and 3, a ledge 50 is spaced inwardly from the upper terminal end of the base. The ledge is substantially circumferentially continuous, although a gap 52 in the ledge cooperates with an outwardly extending tab 54 on the underside of the disk (FIG. 1) to define a keyed connection between the disk and base. That is, the tab must be circumferentially aligned with the gap 52 to allow axial insertion of the tab beneath the ledge 50. Once the disk is rotated from that position, the disk cannot be axially removed from the base until the tab and gap are aligned since the tab rides on the underside of the ledge and prevents pull out.
An internal wall structure 60 is rigidly mounted within the cavity 28 of the base. In the preferred embodiment, the wall structure is integrally molded with the remainder of the base. The wall structure is dimensioned to closely receive a printer cartridge therein. A latching arrangement such as flexible tab 62 (FIGS. 2 and 3) has an inwardly extending lip 64 that extends over a shoulder 66 (FIG. 1) of the printer cartridge once the cartridge is completely received therein. This provides for proper orientation of the printer cartridge in the base, and, in fact, the walled structure is so dimensioned as to be permitted to receive the printer cartridge in only a single orientation.
For reasons which will become more apparent below, the walled structure and base are designed to locate an equalize opening 70 generally along the axial centerline of the refill assembly A. The refill opening 72, on the other hand, is radially offset from the centerline. As is known in the art, the equalize opening 70 communicates with one or more inflatable bladders (not shown) within a base 74 of the printer cartridge. The bladders are normally urged to a deflated condition by one or more springs that compress the bladders. Again, particular details of the structure and operation of a printer cartridge are well known in the art and generally form no part of the subject invention.
Also disposed in the base is a first seal member 80 that is located within the walled structure 60 and adjacent the closed end 24 of the base (FIG. 1). The first seal member defines a nozzle seal that presses against small openings that define the nozzles in the printer cartridge when the cartridge is disposed in latched relation within the wall structure.
An overflow reservoir 82 is defined in a removable wall member 84, and particular details of the reservoir will be described below. A second seal member 86 is carried by a flange 88 of the wall member 84 to define a bubbler seal and covers the vent hole in the base of the printer cartridge. Again, once the printer cartridge is disposed in latched relation within the wall structure, the second seal member 86 closes the vent hole (not shown) in the bottom portion of the printer cartridge.
With continued reference to FIG. 1, and additional reference to FIGS. 4-8, the structure and operation of the individual stations located on the rotatable disk will be described in greater detail. According to the preferred arrangement, four individual stations are located on the disk. The first station is best shown in FIG. 4. It comprises a plunger or pusher member 100 received in an associated well 102. Interposed between the pusher member and the well is a spring that biases the pusher member outwardly away from the platform of the disk member. As shown in FIG. 1, the pusher member includes a stem 104 that extends through an opening in the base of the well and through the platform 34 of the disk. The opening is defined at a preselected radial location from the central axis of the refill assembly. Specifically, it is spaced from the central axis by a dimension that is the same dimension from the centerline as the refill opening is spaced from the equalize opening in the printer cartridge. In this manner, when the first station is rotated to an operative position as shown in FIG. 4, i.e., where the pusher member 100 is accessible through station opening 106 in the cap, the stem 104 is located directly over the refill opening 72 of the printer cartridge latched in the base. Upon depression of the plunger against the outward bias of the spring and into the well 102, the stem 104 is advanced through the underside of the platform and punches an opening in the material that covers the refill opening 72 of the printer cartridge. This is the first stage operation that provides access to the interior cavity by opening a passage through the refill opening 72. The material that is removed from the refill opening is urged inwardly into the printer cartridge cavity and has no adverse impact on later operation of the printer cartridge.
To assure proper orientation of the stations relative to the station opening 106, tabs 108 are provided adjacent the wall 32 at spaced locations corresponding to each individual station. The tabs 108 cooperate with a recess or detent in the cap (not shown) to assure proper rotational position of the disk relative to the printer cartridge.
A finger 110 (FIG. 1) extends from the pusher member and is received in elongated opening 112 formed in the side wall of the well 102 (FIG. 6). The finger and opposite ends of opening 112 cooperate to define upper and lower limits of movement of the pusher member. That is, the spring urges the pusher member outwardly until the finger engages the upper extent of the opening 112. This is the normal, outwardly biased, inoperative position of the pusher member. Actuation or depression of the pusher member against the bias of the spring advances the pusher member and stem 104 downwardly. The downward movement is then limited by finger 110 engaging the bottom end of opening 112, or some other stop surface.
Once the refill opening has been breached, the disk is rotated in the direction shown by arrow 120 (FIG. 4) to bring the second station into alignment with the station opening 106 in the cap. The second station provides a predetermined quantity of air to the bladders in a unique manner. Specifically, an enlarged well 122 extends outwardly from the upper surface of the platform 34. The well defines the housing or cylinder portion of a piston cylinder device. A piston assembly 124 includes a flexible piston member 126 and a piston rod 128. The piston provides sealing engagement with the inner surface of the well 122 so that depression or actuation of button or plunger 130 mounted on the outer end of the piston rod urges the piston toward the platform surface. An opening 132 (FIG. 1) formed in the side wall of the well 122 defines the region where compression of air beneath the piston begins. That is, once the piston passes the bottom of the opening 132, there is only one additional opening through which the air can pass. That opening 132 is formed in the platform (FIG. 8) and is of elongated dimension. A plug 134 is received in the opening and includes a seal 136 around its periphery to provide a closed or sealed passage of air from the radial outer direction toward the central axis of the assembly. The plug 134 has a passage 136 that defines a channel from the base of the well 122 of the second station through an additional seal member, such as O-ring 138, for sealed communication with the equalize opening 70. Thus, air flow is directed axially through the platform, radially along the channel defined in the plug 134, axially through the opening 136, and into the equalize opening of the printer cartridge.
The keyed connection between the disk and the base described above with reference to tab 54 and ledge 50 also adds the additional feature of assuring a sealed connection between the equalize opening 70 of the printer cartridge and the underside of the disk, specifically O-ring 138 (FIG. 1). Thus, even though the disk is rotated from one station to another, the seal between the disk and the equalize opening of the printer cartridge is always maintained until the refill process is complete.
A piston cap or end wall 140 is secured to the upper end of the well 122. It advantageously includes a set of latching fingers 142 that maintain the piston in a depressed position once the button is advanced through the latching fingers. In this manner, air supplied to the bladders of the printer cartridge remains in the bladders until the refill process is complete. Of course other arrangements that maintain the piston in an actuated state can be used as opposed to the latching fingers 142 gripping the upper surface of the plunger 130.
As will be recognized, although the bladders are filled with air during the second station operation, the remainder of the printer cartridge cavity is open to atmosphere via the refill opening 72. Accordingly, the bladders are expanded and consume a portion of the interior cavity of the printer cartridge. The bladders remain in this state until the seal is breached between the underside of the disk and around the equalize opening of the printer cartridge, i.e., upon completion of the refill process.
The third station on the platform is next brought into alignment with the station opening 106 of the cap (FIG. 5). The third station is defined by a semicircular shaped well 150 that extends upwardly from the platform surface. It includes a plurality of integrally formed fingers 152 (FIG. 1) that are adapted to grip the outer surface of an ink tank 154 containing a premeasured quantity of ink used in the refill process. The ink tank 154 is closed by a cap or end wall 156 at one end and a seal member 158 at the other end. The tank seal member 158 is adapted to receive a needle 160 that is positioned in needle housing 162. More particular details of the needle housing 162 are shown in FIGS. 9-11 where the needle has been removed for ease of illustration. The needle housing has a central opening 164 in which the needle is positioned to pierce through seal member 158 when the ink tank is inserted into the needle housing. When tank plug 170 (FIG. 1) is removed from the cap of the ink tank, ink will flow from the tank, through needle, through the central opening 164 of the housing, and into the printer cartridge through refill opening 72. As will be recognized, the needle housing is biased outwardly by a spring (not shown) relative to its well 150. When the ink tank is received in the needle housing, the tank and housing are both advanced axially toward the platform and overcome the bias of the spring. The latch fingers 152 then engage tabs 170 on the outer surface of the ink tank to secure the ink tank in place. This axial movement also advances the bottom end of the needle 160 into the refill opening 72 of the printer cartridge.
When the plug 170 is removed from the ink tank, ink will flow into the printer cartridge cavity and fill the cartridge with a premeasured quantity of ink. Once the ink is emptied from the tank, which may be monitored by the operator because of the transparent material forming the tank, the ink tank may be removed from the third station. The needle housing 162 is then biased outwardly from the platform by the spring and the lower end of the needle retracted from the refill opening 72. Operation of the third station, i.e., the ink refill step, is now complete and the disk may be rotated to align the fourth station with opening 106 in the cap.
An important feature of the third station is best shown in FIGS. 9-11. In addition to the central opening 164, a generally radial passage 174 communicates with a secondary opening 176. If the premeasured quantity of ink is more than can be handled in the printer cartridge cavity, excess ink will back up in opening 164, and be bypassed through radial passage 174 to opening 176. The opening 176 is located adjacent the overflow reservoir 82 in the base so that excess ink is stored therein. Thus, any excess ink is carefully captured by the refill assembly.
Rotation of the disk for positioning the fourth station in its operative location provides for closure of the refill opening. Small beads formed of plastic or other material are inserted into a funnelled well 180 (FIGS. 12 and 13) formed at the fourth station. The funnelled well 180 includes an opening 182 at the radial inner portion. The operator can simply drop the bead into the well, and its funnel shape advances the bead into opening 182. This opening is aligned directly over the refill opening 72 of the printer cartridge. To advance the bead into closing relationship and thereby seal the refill opening, an actuation member 184 having an elongated stem 186 is provided. The actuation member is depressed against the outward bias of spring 188 and the lower end of the stem 186 engages the bead, forcing it through the opening 182, and into operative, sealing relationship with the refill opening 72 of the printer cartridge. Upon release of the actuation member 184, the spring urges the actuation member and stem outwardly to complete the refill process.
The disk is then subsequently rotated to align the first station with the cap opening 106. The piston cap is released from the clips 142 which hold it in a depressed position during movement of the disk from the fourth station to the first station. The clips come in contact with members extending from the underside of the cap. This contact forces the clips 142 radially outward from the piston cap 140 simultaneously releasing the cap 140 to be forced axially upward by spring 190 (FIG. 1). This action deflates the air bladders in the cartridge which in turn, provides a greater volume for ink in the sealed printer cartridge thus exerting a negative or vacuum force on the ink stored in the cartridge. In this manner, ink is less likely to drip from or be expelled through the nozzle openings of the printer cartridge as it is removed from the refill assembly and re-inserted into the printer assembly.
As previously described, rotation of the disk to align the first station with the cap opening also aligns tab 54 with the gap 52 in the ledge so that the disk and cap may be subsequently removed from the base. This provides access to the printer cartridge E which has been heretofore stored in the base. Tab 62 is flexed radially outward so that the lip 64 allows the shoulder 66 of the printer cartridge to be removed axially from the base. Once the disk is separated from the base, the seal between O-ring 138 and the equalize opening 70 of the printer cartridge is broken.
The invention has been described with reference to the preferred embodiment. Obviously, modifications and alterations will occur to others upon a reading and understanding of this specification. It is intended to include all such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof. | An assembly for refilling a printer cartridge includes a base that receives the printer cartridge to be refilled. A lid is located on the base and includes separate stations that sequentially open a refill opening, provide a predetermined amount of air to an equalize opening of the cartridge, dispense ink through the refill opening into the cartridge, and seal the refill opening. In a preferred embodiment, the four stations are mounted on the lid that is rotatable about an axis. The lid forms a seal with the printer cartridge so that air flow to an internal chamber of the cartridge is controlled during the refill process. The base contains any spills, mess, or the like, overcoming the types of problems associated with other ink refill processes and provides an accurate, dependable refill of ink to the printer cartridge. | 1 |
FIELD OF THE INVENTION
[0001] This invention relates to a portable full body exercise apparatus, and in particular, to a compact exercise unit attachable to the leg of a standard swivel chair.
BACKGROUND OF THE INVENTION
[0002] Recent medical studies have shown that lack of physical activity and exercise may cause a significant decrease in both physical and mental state of the human body and mind, as severe as causing heart attack and cancer. In today's modern day environment, due to considerable lack of time, mainly among office workers, it is difficult to get even the minimum amount of such exercise. In order to take part in physical activity, a worker is either forced to move to a certain designated location within the office compound, specifically adapted for physical activity, or commute to a gym or country club outside his work place. Both options take too much time, as a result of which most people remain in constant lack of physical activity.
[0003] In the last few years, increasing awareness and concern for people's health and need of physical exercise have spawned up numerous devices whose sole purpose was to increase “results to time” ratio. However, despite obvious advantages, such devices, much like the devices found in gyms, are usually too big and robust, and take up much space, making them unsuitable for standard size offices. Furthermore, most such devices require a great amount of time for construction and maintenance and are not only space consuming but also hardly transportable in their dismantled form, let alone once assembled.
[0004] A number of compact, portable devices have been developed, providing in office and indoor physical activity, usually by attachment of the device to either a desk or a chair. Some examples of such devices are presented below.
U.S. Pat. No. 6,099,445 discloses an exercise device mounted onto a swivel chair, which comprises a back mechanism of variable height, and a horizontal bar at chair seat height, both for exercising upper body using elastic resistance means, and a front mechanism for training of the legs, using the same kind of resistance. US20040053756 discloses an exercise device attached to a swivel chair, consisting of a set of extendable rod housings encompassing a set of cords and pulleys, for exercising of upper and lower body, allowing variable resistance levels. U.S. Pat. No. 5,324,243 discloses an exercise apparatus mounted on the back rest of a standard chair, which comprises a bar located in a rotatable hub, and elastic resistance means attached to said bar, for training user's arms. U.S. Pat. No. 5,599,260 an exercise device mounted onto the leg of a swivel chair, consisting of a set of pulleys, where ends of said pulleys are attached to elastic resistance means to exercise the arms. In addition, said pulleys comprise a foot brace and are adapted for rolling motion along the floor to exercise the legs.
SUMMARY OF THE INVENTION
[0009] According to one aspect of the present invention, there is provided a compact exercise unit, which comprises a body attachable to a standard swivel chair leg in a removable manner, and having at least one internal cavity and at least one exercise element having a first and a second end, said first end being fixed to the body, said element being extendable between a non-extended position and an extended position in which the second end of the element protrudes from the body, said cavity being adapted at least for storage of said element at least in said non-extended position.
[0010] According to a second aspect of the present invention there is provided a compact exercise unit attachable to a standard swivel chair leg in a removable manner, which comprises at least one exercise element with a first and a second end, said first end being fixed to the unit, said element being extendable between a non-extended position and an extended position in which a portion thereof including said second end is adapted for rotation about a horizontal rotation axis perpendicular to said chair leg, when said unit is mounted thereon.
[0011] The unit according to the second aspect of the invention may have a body as described with respect to the first aspect of the invention. The body in both cases may further comprise one or more compartments adapted for storage of additional exercise elements or any other articles.
[0012] The body is designed to at least partially surround the leg, when the unit is mounted thereon. The internal cavity may occupy the majority of the body and may be adapted for mounting the first end of the exercise element therein.
[0013] The exercise unit may include more than one exercise element and its internal cavity may be adapted for storing at least two of such elements. The internal cavity may comprise more than one storage compartment, in particular for storing exercise elements therein, and their location may be on the sides of the leg, in front of the leg or behind the leg, when the unit is mounted thereon.
[0014] The exercise element in the exercise unit of the first and second aspects of the invention may be of variable length and/or capable of taking different positions, to bring it into at least two different operative states.
[0015] The variable length of the exercise element may be achieved by the element being rigid and having a telescopic design, or being elastic, or due to any appropriate design. Different positions of the exercise element may be achieved by its horizontal rotation about a vertical axis parallel to the chair leg, and/or vertical rotation about a horizontal axis perpendicular to said leg. The element may also be designed to allow adjustment of its height and/or distance of its second end from the chair seat, and it may be adapted for at least upper or lower body exercise in sitting position.
[0016] The second end of the exercise element may be adapted for mounting further components thereon, which may be in the form of an additional exercise device, a part thereof or a supplement to said exercise element. The supplement may be, for example, in the form of a resistance means such as a spring, elastic cord or the like. The additional element may be adapted for storage within the cavity of said body.
[0017] The body of the exercise unit may have a surface area large enough to enable mounting of additional exercise elements thereon. The exercise elements may be of the previously mentioned type, and/or may include handle bars for exercising hands, a stepper, etc. The unit may be further adapted to function as a foot rest and be so mounted on the chair leg as not to interfere with the performance of regular office activity when said element is in its non-extendable position.
[0018] The unit may also be adapted to be connected to a computer equipped with appropriate software and programs, allowing the use of features such as a personal trainer, exercise reminder, exercise games and more, in conjunction with said unit, through an interactive computer interface. For that purpose, the unit may also be equipped with sensors being in communication with said interactive computer interface allowing automatic adjustment of personal, per user, settings such as resistance, angle of arms etc. through said computer interface.
[0019] The unit may be mounted on said chair leg using various means such as a snapping mechanism, screws, clamping mechanism or the like.
[0020] According to a third aspect of the present invention there is provided a compact exercise unit attachable to a standard swivel chair leg in a removable manner, the leg having a predetermined diameter, said unit having a body formed with a longitudinal slot extending perpendicularly to said swivel chair leg, when the unit is mounted thereon, and having a first open end at the circumference of the body, and a second closed end spaced inwardly from said circumference, the width of said slot being not smaller than said predetermined diameter, to allow said slot to receive said leg therein.
[0021] The unit further comprises a clamping mechanism for the fixation of the position of the unit relative to said chair leg, in which the leg is located at the closed end of the slot and clamped thereagainst. The clamping mechanism may comprise a first element adapted for horizontal movement along said slot towards said second end of the slot, and a second element adapted for vertical movement, within said slot.
[0022] The unit according to the current aspect of the invention may have any feature of the unit according to first and/or second aspects of the invention.
[0023] The exercise unit according to any of the above described aspect of the invention may have a design which will advantageously occupy the majority of the vacant space below the seat of a chair corresponding to the area of the chair, with a minimal height along the chair's leg, and will provide a vast variety of exercise opportunities.
BRIEF DESCRIPTION OF THE DRAWINGS
[0024] In order to understand the invention and to see how it may be carried out in practice, several embodiments according to various aspects of the present invention will now be described, by way of non-limiting examples only, with reference to the accompanying drawings, in which:
[0025] FIG. 1A is an isometric view of an exercise unit according to one embodiment of the present invention, wherein exercise elements are in an extended position;
[0026] FIG. 1B is an isometric view of the exercise unit of FIG. 1A with a top cover thereof being removed;
[0027] FIG. 1C is an isometric view of the exercise unit of FIG. 1A when mounted on a chair;
[0028] FIG. 2A is an isometric view of the exercise unit of FIG. 1A with the exercise elements in a non-extended position;
[0029] FIG. 2B is an isometric view of the exercise unit of FIG. 2A with the top cover removed;
[0030] FIG. 2C is an isometric view of the exercise unit of FIG. 2A when mounted on a chair;
[0031] FIG. 3A is an isometric view of the exercise unit shown in FIGS. 1A to 2 C, with front storage compartment removed;
[0032] FIG. 3B is a schematic isometric view of the exercise unit shown in FIGS. 1A to 2 C, mounted on a chair, with all parts, except the base plate and clamping mechanism, being removed;
[0033] FIG. 4 is an isometric view of a spool used as resistance means in the exercise unit shown in FIGS. 1A to 2 C;
[0034] FIG. 5A is an isometric view of one operative state of the exercise unit shown in FIGS. 1A to 2 C;
[0035] FIG. 5B is an isometric view of another operative state of the exercise unit shown in FIG. 5A ;
[0036] FIG. 6A is an isometric view of the exercise unit shown in FIGS. 1A to 2 C with an additional stepper added thereto;
[0037] FIG. 6B is an isometric view of the exercise unit shown in FIG. 6A , when mounted onto a chair;
[0038] FIG. 7A is an isometric view of an exercise unit according to another embodiment of the present invention;
[0039] FIG. 7B is an isometric view of the exercise unit shown in FIG. 7A , when mounted onto a chair;
[0040] FIG. 8 shows an alternative spool which may be mounted, instead of the spool shown in FIG. 4 , onto the exercise elements of the exercise unit shown in FIGS. 1-7 ;
[0041] FIGS. 9A to 9 N illustrate different types of exercises which may be performed by means of the exercise unit shown in FIGS. 1 to 8 ;
[0042] FIG. 10A is an isometric view of an exercise unit according to another embodiment of the present invention, wherein exercise elements are in an extended position;
[0043] FIG. 10B is an isometric view of the exercise unit of FIG. 10A with a top cover thereof being removed;
[0044] FIG. 11A is an isometric view of the exercise unit of FIG. 10A in a non-extended position, with the top cover removed and side storage compartments extended;
[0045] FIG. 11B is a schematic isometric view of the exercise unit shown in FIG. 11A , with all parts, except the base plate, clamping mechanism, and wing elements being removed;
[0046] FIG. 12A is a rear isometric view of the exercise unit in FIG. 10A , with the adjustment lever and utility cover in a closed position;
[0047] FIG. 12B is a rear isometric view of the exercise unit in FIG. 10A , with the lever and cover of the positioning mechanism in an open position; and
[0048] FIG. 13 is a rear isometric view of the exercise unit in FIG. 10A , in a non-extended position.
DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS
[0049] FIG. 1A and FIG. 1B illustrate a compact exercise unit 10 according to one embodiment of the present invention, which is adapted for mounting on a leg of a swivel chair as shown in FIG. 1C .
[0050] The exercise unit 10 comprises a body 50 , two extendable front arms 20 , two extendable rear arms 30 , an extendable upper bar 40 and four spools 60 mounted on the arms and the bar.
[0051] The body 50 comprises a base plate 51 and a top cover 52 with a cavity 53 defined therebetween. The body has an axis of symmetry 100 and has a dimension in a plane perpendicular to the axis of symmetry 100 , essentially greater than the distance between the upper and lower plates.
[0052] The base plate 51 and top cover 52 both have aligned narrow longitudinal slots 54 , extending from the center of the body 50 towards its circumference. Housed therebetween is a clamping mechanism 55 adapted for mounting the exercise unit 10 onto a leg of the swivel chair ( FIG. 1C ), so that the body 50 surrounds the leg, and fixes the unit into place. In addition, the body 50 comprises a front storage compartment 56 and two side storage compartments 57 . The compartments are adapted for accommodating various exercise elements such as elastic cords, etc. but may also be used for storage of various artifacts. The side compartments 57 may be modified to be hold additional apparatus as will be explained later on.
[0053] The two front arms 20 are connected to the back of the body 50 , each arm 20 having a hinge 25 allowing it to rotate horizontally and thereby to protrude from the body 50 . Each arm has a telescopic design allowing its longitudinal extension. Each arm 20 is comprised of three segments: a first internal 22 a , an intermediate 22 b , and an external 22 c . The first internal segment 22 a is formed with a compartment 23 of a third partially circular form, adapted to be flush against the rims 51 ′ and 52 ′ of the base plate 51 and top cover 52 when the arms 20 are in a position parallel to each other. The third external segment 22 c of each arm 20 may be adapted for mounting thereon a resistance means in the form of a spool 60 or the like, which will be defined in more detail later with reference to FIGS. 4 and 8 . The compartment 23 may be used for storage of various artifacts.
[0054] The two rear telescopic arms 30 each comprises one internal segment 31 fixed to the body 5 , one intermediate segment 32 horizontally movable with respect to the internal segment 31 , and three segments 33 a ; 33 b ; 33 c , constituting a telescopic end section 33 connected to the segment 32 by means of a joint 35 . The joint 35 is adapted to allow vertical rotation of the end section 33 of each arm about a horizontal axis 36 and is capable of sliding in and out of the segment 32 along with the end section 33 .
[0055] The upper bar 40 is attached to the segments 32 c of the rear arms 30 and it comprises a longitudinal horizontal bridge 42 accommodating two horizontal back bars 44 adapted to be laterally extended outside the bridge, along its longitudinal direction. Each of the back bars 42 is adapted for mounting thereon a resistance means in the form of a spool 60 similar to the one mounted on the front arms 20 .
[0056] FIG. 1C shows the exercise unit 10 , in its one operative state, mounted on a leg 72 of a standard swivel chair 70 , such that the leg 72 is inserted into the longitudinal slot 54 of the body 50 and clamped into place using the clamping mechanism 55 as will be described in more detail below with reference to FIG. 3 . In FIG. 1C , one operative state of the unit 10 is shown, wherein the front arms 20 are extended both longitudinally and angularly to create a 120° angle between them. The rear arms 30 are also extended longitudinally and their end section 33 is tilted at 90° with respect to the intermediate segment 31 .
[0057] FIG. 5A and FIG. 5B show two additional operative states of the unit 10 wherein the angle between the front arms 20 is 0° and 60° respectively. It should be noted that a vast number of operative states is available to the user through various angles between the front arms 20 . In addition, although not shown, the back arms 30 may also tilt in various angles to provide additional operative states. Furthermore, the length of each of the arms 20 ; 30 and bars 44 may be adjusted for the convenience of the user.
[0058] FIG. 4 shows the spool 60 used as resistance means in the exercise unit 10 . The spool 60 comprises a round housing 61 with discs 62 on both ends. The housing further comprises an inner rod (not shown) and a slot 63 . An elastic strap 64 adapted for exercise is wound around the rod within the housing 61 and its tip comes out of the slot 63 . A tab 65 is connected to the tip of the strap 64 and has a hole 66 in its center. A ring 67 is passed through the hole 66 and connects the tab 65 to a handle comprising a band 68 and a hand grip 69 . The spool is also connected to a connector 161 having a hole 162 adapted to connect the spool 60 to either the front arms 20 or the back bars 44 . In operation, pulling on the handle stretches the elastic strap 64 , allowing physical exercise. It should be clear that the spool 60 may have any other design known in the art.
[0059] In operation, the chair occupant is seated on the seat 74 and may use each one of the four spools 60 to perform either upper or lower body exercise by pulling on the straps 64 using the hand grips 69 with either hands or legs. The structure of the exercise unit 10 allows the user a wide variety of exercises, for example, pulling on the straps 64 either above the back rest 76 or from its sides, with the exercise elements being either in.
[0060] The exercise elements of the unit 10 are easily retractable into their inoperative, non-extended position as shown in FIGS. 2A and 2B .
[0061] In particular, the back bars 44 are adapted to be retracted into the bridge 42 , whereas the rear arms 30 including the upper bar 40 , and the front arms 20 are adapted to be retracted into the cavity 53 of the body 50 with the circular portion of the compartment 23 of each of the front arms 20 being flush against the circumference of the base plate 51 and top cover 52 . The spools 60 are removed from the front arms 20 to be stored in the front storage compartment 56 . The spools 60 connected to the back bars 44 may be left slightly protruding from the body 50 of the exercise unit 10 , or alternatively they may also be removed and stored away, e.g. in the side storage compartments 57 .
[0062] FIG. 2C shows the exercise unit 10 in a non-extended position mounted on a chair 70 . In this position, the unit 10 does not protrude outside the circumference of the seat 76 of the chair 70 , thus on the one hand allowing performance of regular office activity, and on the other hand efficiently utilizing the space under the chair 70 for storing its exercise elements. The unit 10 may also function in this position as a foot rest.
[0063] It should be noted that the unit 10 may be used for exercise in a non-extended position since the spools 60 may be available to the user, if not removed from the arms, even when the front arms 20 and the back arms 30 are retracted into the cavity 53 .
[0064] FIG. 3A shows an isometric view of the exercise unit shown in FIGS. 1A to 2 C, with the front storage compartment 56 removed and FIG. 3B shows a schematic isometric view of the exercise unit shown in FIGS. 1A to 2 C, mounted on a chair, with all parts, except the base plate and clamping mechanism, being removed. In both figures, the clamping mechanism 55 comprising a moving jaw 55 a having a semi circular recess 58 adapted to press against the chair leg 72 (as seen in FIG. 3B ) in order to clamp it against the semi circular end of the longitudinal slot 54 , a fixed jaw 55 b with a threaded hole, and a lead bolt 55 c going therethrough, connected to the moving jaw 55 a.
[0065] During assembly, in order to mount the body 50 on the chair leg 72 , the front storage 65 , and the clamping mechanism 55 are first removed. The chair leg 72 is inserted into the slot 54 at its open end and is moved towards the closed end of the slot 54 until it abuts it. The moving jaw 55 a is then inserted between the base plate 51 and the top cover 52 and is driven along the slot 54 until it engages the chair leg 72 . Once the moving jaw 55 a has engaged the leg, the fixed jaw 55 b is inserted between the base plate 51 and the top cover, and is driven along the slot 54 until it enters vertically into the recesses of the base plate 51 in a direction perpendicular to the slot 54 . The lead bolt 55 c is then driven through the threaded hole of the fixed jaw 55 b . When the bolt 55 c is turned, it moves forward, and since the jaw 55 b is fixed, the end result is displacement of the moving jaw 55 a towards the chair leg 72 . The bolt 55 c is turned until the unit 10 is secured to the chair leg 72 .
[0066] Thus, after assembly, the clamping mechanism 55 is located between the base plate 51 and the top cover 25 of the unit 10 (shown here with the front storage space 56 removed) securely clamping the chair leg 72 , and the fixed jaw 55 b is positioned in recesses 59 in the base plate 51 .
[0067] FIG. 6A and FIG. 6B show the exercise unit 10 wherein a stepper 80 is mounted on the front arms 20 , as an additional exercise element. In this case, the spools (not shown) are removed from the front arms 20 and instead, the stepper is slipped onto the arms 20 .
[0068] The stepper 80 comprises two bars 82 connected to a stepper bridge 84 , to which levers 86 are connected on each side. Each lever 86 is connected to the bridge 84 on one end of the lever 86 and supports a stepper pad 88 located at the other end of the lever 86 .
[0069] In operation, the chair occupant is seated on the seat 72 and places his feet on the stepper pads 88 . In this position it is then possible to perform several exercises for the leg, which may, among other things, simulate riding a bicycle.
[0070] FIG. 7A and FIG. 7B show another embodiment of the exercise unit 10 wherein the side storage compartments 57 have been modified to allow connection thereto of an additional exercise element such as a skiing-type apparatus 90 . The skiing-type apparatus 90 comprises two ski bars 92 with bar grips 94 at one end, the ski bars 92 being connected to the body 50 on the other end using a connector 96 .
[0071] In operation, the user seated in the chair 70 , may exercise his upper body by moving the ski bars with his hands, simulating various sport activities, mainly skiing and rowing.
[0072] FIG. 8 shows a variation 260 of the spool previously described. The spool 260 comprises a housing 261 with an inner rod (not shown) and a slot 263 . An elastic strap 264 is wound around the inner rod and its slip comes out of the slot 263 . A tab 265 is connected to the slip and has a hole 266 in its center. On the opposite side of the spool, a band 268 is attached connected to a hand grip 269 . The spool additionally has a lock button 262 adapted to adjust the length of the strap 264 . The spool 260 may be further used independently to perform various exercises, wherein the spool 260 may be connected to a desk, a door etc. The spool 260 may even be connected to another hand grip 269 to be used to exercise upper or lower body without the need for an object allowing attachment of the spool 260 thereto.
[0073] With reference to FIGS. 9A to 9 N, different types of exercises may be performed by means of the exercise unit described above. In particular:
[0074] Chest and shoulder exercises (as shown in FIG. 9A to 9 C);
[0075] Arms and Biceps exercises (as shown in FIGS. 9 D and 9 E);
[0076] Diagonal muscle exercises (as shown in FIG. 9F );
[0077] Shoulder and back exercises (as shown in FIG. 9G );
[0078] Back arm and shoulder exercises (as shown in FIG. 9H );
[0079] Arm, shoulder and chest exercises (as shown in FIGS. 9 I and 9 J);
[0080] Back, stomach and shoulder exercises (as shown in FIGS. 9 K and 9 L);
[0081] Side and hips exercises (as shown in FIG. 9M ); and
[0082] Stomach exercises (as shown in FIG. 9N ).
[0083] FIGS. 10 to 13 illustrate a compact exercise unit 10 according to another embodiment of the present invention, which is adapted for mounting on a leg of a swivel chair.
[0084] The exercise unit 101 comprises a body 500 , two extendable arms 200 , and spools 60 mounted on the arms. The body 500 comprises a base plate 510 and a top cover 520 with a cavity 530 defined therebetween. The body has an axis of symmetry 1000 and has a dimension in a plane perpendicular to the axis of symmetry, essentially greater than the distance between the upper and lower plates.
[0085] The exercise unit 101 is essentially similar to the exercise unit 10 according to the previously described embodiment, with the exception that it comprises only two arms 200 , as opposed to two front arms 20 and two back arms 30 in the previous embodiment.
[0086] Each arm 200 is connected to a wing element 300 of partially circular form, which is connected in turn to the back of the body 500 via a hinge defining a vertical axis 350 allowing it to rotate horizontally and thereby to protrude from the body 500 . The wing element 300 is formed with a side compartment 310 of a partially circular form, adapted to be flush against the rims 312 and 314 of the wing element 300 when in a closed position. The side compartment 310 may be used for storage of various artifacts.
[0087] Each arm 200 is connected to the wing element 300 through a hinge defining a horizontal axis 250 , allowing the arm 200 to rotate vertically about the axis. Each arm 200 has a telescopic design allowing its longitudinal extension and is comprised of three segments: a first internal 210 , connected to the wing 300 , an intermediate 220 , and an external 230 . The third external segment 230 of each arm 200 may be adapted for mounting thereon a resistance means in the form of a spool 60 or the like, as previously defined in more detail with reference to FIGS. 4 and 8 .
[0088] Referring to FIG. 10B , the wing elements 300 are connected to each other via a gear mechanism 400 , comprising a set of two discs 410 with interlocking teeth 415 . The disc 410 and the wing element 300 rotate about the same vertical axis 350 . The discs 410 may be fixed in a certain position as will be explained later. The rotation of the wing elements 300 about their vertical axis 350 , along with the vertical rotation of the arms 200 about their horizontal axis 250 , allows the arms 200 to be positioned at almost any angle with respect to the occupant of the chair 70 .
[0089] Referring to FIG. 11A , the side compartments 310 are in an extended position, and protrude from the body 500 of the exercise unit 101 . The compartments rotate about the horizontal axis 315 . The clamping mechanism 550 now comprises a moving jaw 552 , a fixed jaw 554 , a back support 556 and a lead bold 558 . The operation of the clamping mechanism 550 is essentially the same as the clamping mechanism 55 according to the previous embodiments of the present invention.
[0090] The discs 420 are fixed by pins 436 , preventing them from rotating, thus keeping the arms 200 at a fixed position. The lever 430 is now at a raised position, supporting the pins 436 .
[0091] With reference to FIG. 11B , the positioning mechanism 430 is shown comprising a lever 432 , an end plate 433 at its one end, the lever being formed with a major indent 434 a and a minor indent 434 b , the use of which will be explained in detail later. The lever 430 further comprises two pin housings 435 , in which two positioning pins 436 are positioned. The lever 430 is formed with a horizontal member 437 at its other end, adapted to support the two housings 435 . The positioning pins 436 are adapted to pass through holes 420 of the discs 410 (visible in FIG. 11A ) into the housings 435 , thus preventing the discs from rotating. The wing elements 300 are positioned on two plate members 330 , connected to the base plate 510 .
[0092] Referring now to FIG. 12A , the latch 439 of the cover 438 is positioned in the minor indent 434 b of the lever 432 . In this position, the horizontal member 437 is raised, causing the housings 435 to push the positioning pins 436 in an upwards direction, so that they fit into the holes 420 of the discs 410 (shown previous Figs.).
[0093] When the cover 438 is in an open position ( FIG. 12B ), the latch 439 displaces into the major indent 434 a , thus pushing the lever 432 in a downwards direction, subsequently causing the horizontal member 437 to move in the same direction, lowering the housings 435 and positioning pins 436 . This allows rotation of the discs 410 , and their re-positioning at a desired angle.
[0094] FIG. 13 shows the exercise unit 101 in a non-extended position. The cover 438 is lowered to a closed position, and the arms 200 are stored within the cavity 530 of the body 500 .
[0095] It should be appreciated that mounting of the unit, as well as all the additional exercise elements, and exercises as specified for the exercise unit 10 as described according to the previous embodiment of the present invention apply to the exercise unit 101 as described with regards to the present embodiment as well.
[0096] Those skilled in the art to which this invention pertains will readily appreciate that numerous changes, variations and modifications can be made without departing from the scope of the invention mutatis mutandis. | According to one aspect of the present invention, there is provided a compact exercise unit, which comprises a body attachable to a standard swivel chair leg in a removable manner. The body has at least one internal cavity and at least one exercise element. The exercise element has a first and a second end, the first end being fixed to the body. The element is extendable between a non-extended position and an extended position in which the second end of the element protrudes from the body. The cavity being adapted at least for storage of said element at least in said non-extended position. | 0 |
FIELD OF THE INVENTION
This invention relates to the handling of fluorescent bulbs, and in particular to methods and apparatus for holding and transporting fluorescent bulbs.
Fluorescent bulbs are widely used in commercial and residential settings. A fluorescent bulb is a glass tube with electrodes on the end. Fluorescent bulbs contain a small quantity of mercury that can be harmful to the environment and to human health when improperly managed. Mercury is regulated under RCRA, which is administered by the US Environmental Protection Agency. Under current Federal law, mercury-containing lamps such as fluorescent may be hazardous waste. To prevent toxic material from contaminating the environment, fluorescent bulbs must be disposed of responsibly.
While fluorescent bulbs can come in a variety of sizes and shapes, the majority of bulbs are either 1⅜ inches in diameter and either 48 inches, 72 inches, or 96 inches long. Because they are fragile and because of their size, fluorescent bulbs can be hard to handle. A broken bulb presents hazards not just from injury from the broken glass, but also from contamination from the mercury vapor in the bulb. It is convenient to collect and hold fluorescent bulbs in an elongate container to protect the bulbs from breakage and contain the contents if there is a breakage. However, it is difficult to fully load a container that is upright or on its side, the bulbs tend to move within the box, breaking and/or making it difficult to load additional bulbs into the container.
SUMMARY OF THE INVENTION
The present invention relates to a method of, and apparatus for, handling fluorescent bulbs, to facilitate the fast and efficient collection and disposal, while minimizing the risk of breakage, and the attendant risks of injury and contamination.
Generally, the method of this invention comprises supporting a container for the fluorescent bulbs at an angle while it is being filled. This allows the bulbs to be arranged in the most efficiently packed arrangement, and reduces the incidence of the bulbs moving before the container is filled. In the preferred embodiment, the container is held at an angle of between about 30° and about 60°, and more preferably at an angle of between about 35° and about 50°, and most preferably at an angle of between about 400 and about 45°.
Generally, the apparatus of this invention comprises a cart having a support having a sloped support surface for supporting a container for collecting fluorescent bulbs at an angle, and maintaining the container at that angle while the container is moved about as it is filled. The cart preferably holds the container at an angle of between about 30° and about 60°, and more preferably at an angle of between about 35° and about 50°, and most preferably at an angle of between about 40° and about 45°.
In the preferred embodiment, the cart comprises a base having a first and second ends, a first pair of wheels on the first end of the base, a second pair of wheels at the second end of the base. A strut, having first and second ends, is hingedly mounted at its first end to the first end of the base. A support having first and second ends, hingedly mounted at its first end to the second end of the base. The hinged mounting of the strut and support permit the strut and the support to swing between a folded position, in which the strut and the support lie generally parallel to the base, and an extended position in which the second end of the strut engages the support to hold the support at an angle of between about 30° and about 60° with respect to the base, more preferably at an angle of between about 350 and about 50°, and most preferably at an angle of between about 40° and about 45°. The support surface is preferably curved to support a cylindrical collection container.
Thus the method and apparatus of the present invention provide a fast and inexpensive way to collect fluorescent bulbs by holding the collection container in a preferred orientation while that container is being filled. This makes it easier to more densely pack the container, and reduces the risk that bulbs will be broken while the container is moved about as it is being filled, and as bulbs are inserted into the container. %
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side elevation view of a cart constructed according to the principles of this invention in its extended position;
FIG. 2 is a side elevation view of a cart constructed according to the principles of this invention in its collapsed position;
FIG. 3 is a left end elevation view of the cart as shown in FIG. 2;
FIG. 4 is bottom plan view of the cart as shown in FIG. 2;
FIG. 5 is bottom plan view of the base of the cart;
FIG. 6 is a transverse cross-sectional view taken along the plane of line 6 — 6 in FIG. 5;
FIG. 7 is a longitudinal cross-sectional view taken along the plane of line 7 — 7 in FIG. 5;
FIG. 8 is a top plan view of the strut of the cart;
FIG. 9 is a transverse cross-sectional view of the strut, taken along the plane of line 9 — 9 in FIG. 8;
FIG. 10 is a longitudinal cross-sectional view of the strut, taken along the plane of line 10 — 10 in FIG. 8;
FIG. 11 is a top plan view of the support of the cart;
FIG. 12 is a end left elevation view of the support shown in FIG. 1; and
FIG. 13 is a side elevation view of the support.
Corresponding reference numerals indicate corresponding parts throughout the several view of the drawings.
DESCRIPTION OF THE PREFERRED EMBODIMENT
A cart constructed in accordance with the principles of this invention, and useful in the methods of this invention is indicated generally as 20 in FIGS. 1-4. The cart 20 comprises a base 22 , a strut 24 , and a support 26 , and as first pair of wheels 28 on axle 30 at one end of the base, and a second pair of wheels 32 on axle 34 at the other end of the base. In the preferred embodiment, the strut 24 and the support 26 are hingedly connected to the base 22 so that they can be pivoted relative to the base between an extended position (shown in FIG. 1) and a collapsed position (shown in FIGS. 2 - 4 ).
As shown in FIGS. 5-7, the base 22 has a first end 40 and a second end 42 . The base 22 comprises first and second longitudinally extending rails 44 and 46 . Three transverse members 48 , 50 , and 52 extend between the first and second rails 44 and 46 . The ends of the rails 44 and 46 adjacent the first end 40 of the base ends slope generally upwardly, and have aligned holes 54 therethrough. Similarly, the ends of the rails 44 and 46 adjacent the second end 42 of the base slope generally upwardly, and have aligned holed 56 therein. There are grooves 58 and 60 formed in the bottom and top of the rail 44 , and groves 62 and 64 formed in the bottom and top of the rail 46 . The base 22 can be made of molded plastic, for example a polyethylene plastic, so that it is tough, durable, and strong, yet light weight.
As shown in FIGS. 8-10, the strut 24 has a first end 70 and a second end 72 . The strut 24 comprises first and second longitudinally extending rails 74 and 76 . Three transverse members 78 , 80 and 82 extend between the first and second rails 74 and 76 . The ends of rails 74 and 76 adjacent the first end 70 have aligned holes 78 . The ends of the rails 74 and 76 adjacent the second end 72 bend out of the plane of the strut 70 . There is a groove 80 on the underside of the rail 74 , and a groove 82 on the underside of the rail 76 . The strut 24 can be made of molded plastic, for example a polyethylene plastic, so that it is tough, durable, and strong, yet light weight.
As shown in FIGS. 11-13, the support 26 has a first end 90 and a second end 92 . The support 26 has a tabs 94 projecting from the bottorn, adjacent the second end 92 . There are aligned holes 96 through the tabs 94 . The support 90 includes a support surface for supporting a container of fluorescent bulbs. In the preferred embodiment the support surface includes a generally planar surface 98 for engaging the bottom of the container, and a curved surface 100 for engaging the sidewall of the container. The support has a recess 102 on its underside for receiving the second end 72 of the strut, so that the strut holds the support at an angle of between about 30′ and about 60°, and more preferably at an angle of between about 35° and about 50°, and still more preferably at an angle of between about 40′ and about 45′. This is indicated as angle A in FIG. 1 . In the preferred embodiment, there are at least two recesses 102 so that the angle A can be adjusted by moving the second end 72 from one recess 102 to another. There is a handgrip 104 formed on the underside of the support 26 . The support 26 can be made of molded plastic, for example a polyethylene plastic, so that it is tough, durable, and strong, yet light weight. A belt 106 can be provided with a buckle, or more preferably a closure of mating hook and loop type fastening material, so secure a container on the support.
Referring to FIGS. 1 through 4, ends of the rails 74 and 76 at the first end of the strut 24 fit within the ends of the rails 44 and 46 at the first end of the base 22 . The axle 30 extends through the aligned holes 78 in the strut and 54 in the base, hingedly mounting the first end 70 of the strut 24 to the first end 40 of the base 22 . As described above, the wheels 28 are mounted on the ends of the axle 104 . Similarly, the tabs 94 on the support 26 fit between the rails 44 and 46 at the second of the base. The axle 34 extends through holes 56 in the ends of the rails 46 and 46 at the second end of base 22 and through holes 96 in tabs 94 on the support 26 , hingedly mounted the second end of the support and the second end of the base. As described above, wheels 32 are mounted on the ends of the axle 106 .
Thus, the cart 20 can be folded into its collapsed state by disengaging the strut and the support, folding the strut flush against the base, and then folding the support over the base and strut. However, the cart can be quickly assembled into its operating state by unfolding the support, unfolding the strut and engaging the second end of the strut in the recess 102 in the underside of the support. The support 26 holds a container, such a drum at an appropriate angle for loading the container with fluorescent bulbs, and maintaining the container in this orientation as its is moved from place to place until the container is filled | A cart for supporting a container in an appropriate orientation for holding fluorescent light bulbs includes a support at an angle of between about 30° and about 60°. A method of handling fluorescent bulbs includes supporting an elongate, open ended container for the fluorescent bulbs on a wheeled cart at an angle of between about 30° and about 60° to permit efficient loading and unloading of the bulbs in the open container, and retaining the container in that orientation until the container is fully loaded. | 1 |
TECHNICAL FIELD
[0001] The present invention relates to a closure suitable for dispensing pourable product from a container. More specifically, the present invention is directed to a “twist to open” type closure operated by a twisting action.
BACKGROUND OF THE INVENTION
[0002] Dispensing closures for containers are commonly known in the art and may be based on various opening mechanisms such as “push and turn”, “twist and turn”, “twist to open” or “push and pull”. Those closures are commonly used in combination with containers designed to contain products such as food, beverages, personal care products, pharmaceutical or cosmetic products. Typical types of dispensing closures are for example described in U.S. Pat. No. 6,202,876 (push and twist), U.S. Pat. No. 5,305,932 (snap-on), U.S. Pat. No. 2,004,015507 (push and pull) or in WO 2004/110889 (push to open). The specific type of “twist to open” closures is described for example in U.S. Pat. No. 5,305,932; EP-B1-0 378 488; WO 00/30949; EP-A1-0 417 891 and in WO 03/050033.
[0003] Although the above-types of closures will generally function satisfactorily in the applications for which they are designed, they typically only permit slow dispensing of limited amount of fluids. However, in certain circumstances, it is required to dispense the contained products much faster and in a relatively large quantity. This is typically the case in the context of liquid detergent containers. It has indeed been discovered that the users of containers equipped with the corresponding dispensing closures primarily seek for the fastest possible delivery of the contained liquid detergent into an appliance or receptacle. Most commonly used closures for containers adapted for delivering liquid detergent compositions, which are typically viscous liquids by nature, are described e.g. in EP-B1-0 109 704. Those dispensing closures typically consist of two separate parts: a spouted transition piece and a screw-type cap. Although the spouted piece allows for precise pouring of the viscous liquid into the intended receptacle, the cap is however often seen as difficult and/or too long to open and may easily get lost.
[0004] Another drawback associated with the use of the above dispensing system is that under usage, liquid detergent compositions may be spilled in the area where liquid detergent is consumed and/or on the user's hands which may lead to skin irritation or even burns. This often occurs when the above-mentioned cap is also used as a dosing means.
[0005] It is therefore an objective of the present invention to provide a dispensing closure suitable for dispensing pourable product from a container which provides fast dispensing of the contained product, which is easy-to-use, mess-free and which overcomes the above-mentioned drawbacks.
[0006] It has now been found that the above objective can be met by providing a dispensing closure 1 according to the present invention.
[0007] Advantageously, the dispensing closure 1 according to the present invention exhibits improved opening/closing ergonomics. A further advantage associated with the dispensing closure 1 according to the present invention is that it provides excellent sealing vis-à-vis the contained product.
[0008] It is still another advantage that, due its particular configuration, the dispensing closure 1 of the present invention provides more convenient way of dispensing pourable product and allows better viewing of the amount of product being dispensed.
[0009] It is still a further advantage that the dispensing closure 1 of the present invention requires a minimum number of components, which greatly facilitates its manufacture and assembly, and substantially reduces the associated production costs. In addition, the dispensing closure 1 of the present invention provides a more aesthetic appeal when compared to similar closures known in the art, and contributes to provide the user with a more pleasant experience while operating domestic tasks.
[0010] Advantageously, the dispensing closure 1 according to the present invention does not require any modification of the container 2 on which it is mounted, for the dispensing closure 1 to become operable.
[0011] Other advantages and more specific properties of the dispensing closure 1 according to the present invention will be clear after reading the following description of the invention in combination with the attached drawings.
SUMMARY OF THE INVENTION
[0012] The present invention relates to a dispensing closure 1 suitable for being mounted on a container 2 , the container 2 having a dispensing opening 3 and being suitable for containing a pourable product in its interior volume, wherein the dispensing closure 1 comprises:
(a) a base member 7 comprising a means for attachment 6 to said container 2 , a draining canal 12 adapted to communicate with the interior volume of the container 2 , a discharging means 13 and a hollow sleeve 15 ; wherein the hollow sleeve 15 is adapted to communicate with the draining canal 12 and comprises a dispensing aperture 18 capable of dispensing the pourable product. (b) a cap 19 comprising a cap top 20 and a barrel 21 extending downwardly from the cap top 20 , whereby the cap top 20 is capable of covering the discharging means 13 in a tight manner vis-à-vis the content of the container 2 ; (c) complementary means 27 , 28 of raising and lowering the cap 19 by rotation thereof, wherein the complementary means 27 , 28 are located in the barrel 21 and the hollow sleeve 15 , and are adapted to switch the cap 19 from a lower position wherein said discharging means 13 is covered by the cap top 20 and the dispensing aperture 18 is obstructed by the barrel 21 , and an upper position wherein the discharging means 13 is uncovered and the dispensing aperture 18 is unobstructed.
[0016] In another embodiment, the present invention is directed to a container closure assembly, comprising:
(a) a container 2 having a body portion 4 for holding container content, a lower closed end for supporting the container 2 , an upper end including a means of attachment 30 thereon adapted to receive and affix a dispensing closure for containers; and (b) a dispensing closure 1 as above-indicated, mounted on the container 2 .
[0019] The present invention further encompasses a method of dispensing the content of a container 2 comprising the steps of:
(a) providing a container closure assembly as above-described, wherein the cap 19 is in its lower position; (b) rotating the cap 19 so as to raise the cap 19 to its upper position; (c) pouring the required amount of the container content through the discharging means 13 ; (d) rotating the cap 19 so as to lower the cap 19 back towards its lower position.
BRIEF DESCRIPTION OF THE DRAWINGS
[0024] FIG. 1 is a cross-section view of a container closure assembly according to the present invention. The assembly comprising a container 2 onto which is mounted a dispensing closure 1 according to another embodiment of the invention.
[0025] FIG. 2 is a top perspective view of a dispensing closure 1 according to the invention in its lower/closed position.
[0026] FIG. 3 is a top perspective view of a dispensing closure 1 according to the invention in its upper/open position.
[0027] FIG. 4 is a bottom perspective view of the cap 19 for use in a dispensing closure 1 according to the invention.
[0028] FIG. 5 is a top perspective view of the base member 7 for use in a dispensing closure 1 according to the invention.
[0029] FIG. 6 is a top view of a dispensing closure 1 according to the invention in its lower/closed position.
[0030] FIG. 7 is a top view of a dispensing closure 1 according to the invention in its upper/open position.
[0031] FIG. 8 is a side view of a dispensing closure 1 according to the invention in its lower/closed position.
[0032] FIG. 9 is a side view of a dispensing closure 1 according to the invention in its upper/open position.
[0033] FIG. 10 is a cross-sectional side view of a dispensing closure 1 according to the invention in its lower/closed position.
[0034] FIG. 11 is a cross-sectional side view of a dispensing closure 1 according to the invention in its upper/open position.
DETAILED DESCRIPTION OF THE INVENTION
[0035] For the purposes of promoting and understanding the principles of the present invention, reference will be made to the embodiment illustrated in the drawings and specific language will be used to describe the same. While this invention is susceptible of embodiments in many different forms, this specification and the accompanying drawings discloses specific forms as examples of the invention. However, the invention is not intended to be limited to the embodiment so described.
[0036] In a first embodiment, the present invention is directed to a dispensing closure 1 suitable for being mounted onto a container 2 having a dispensing opening 3 .
[0037] Referring now to FIG. 1 , a dispensing closure 1 according to a first embodiment of the invention is represented which is mounted onto a container 2 .
[0000] Container 2
[0038] In a preferred embodiment, the container 2 comprises a body portion 4 for holding container content, a lower closed end for supporting said container 2 , an upper end including a neck 5 delimiting a dispensing opening 3 . The dispensing closure 1 of the present invention may be securely mounted onto said container 2 , via its base member 7 , using any means of attachment commonly know to those skilled in the art including cooperative threads, crimping, clipping means, heat sealing force fitting, clasp elements, snap-fit bead, groove arrangements, and mixtures thereof.
[0039] Preferably, the dispensing closure 1 of the invention is provided with an inner female thread 6 typically located in the base member 7 , as described hereinafter, and the container neck 5 is provided with a male thread 30 formed adjacent its dispensing opening 3 . Typically, the dispensing closure 1 is mounted onto the container 2 with the female thread 6 of the base member 7 screwed on the male thread 30 of the container 2 .
[0040] Alternatively, the container 2 may not need to have a neck 5 . Instead the container 2 may consist of a just a body portion 4 with a dispensing opening 3 . The dispensing closure 1 of the present invention is suitable for use with a variety of conventional or special containers having various designs, the details of which, although not illustrated or described, would be apparent to those skilled in the art. The container 2 may have a rigid wall or walls, or may have a somewhat flexible wall or walls.
[0041] In a preferred aspect of the invention, the dispensing closure 1 is a separate element which is adapted to be removably or non-removably mounted, via its base member 7 , to a previously manufactured container 2 which has a dispensing opening 3 to the container interior. The dispensing closure 1 is adapted to be used with a container 2 having a dispensing opening 3 to provide access to the container interior volume and to a product contained therein, which is preferably a pourable product. However, the dispensing closure 1 of the invention may be used with many products, including but not limited to, relatively low or high viscosity liquids, creams, gels, suspensions, mixtures, lotions, pastes, particulates, granular products, and mixtures thereof. Typical products for use in the present invention may be those constituting a food product, a personal care product, an industrial or household cleaning product, or other compositions of matter for use in activities involving manufacturing, commercial or household maintenance, construction, agriculture.
[0042] Preferably, said pourable product is a liquid composition, more preferably a viscous liquid composition, most preferably a laundry liquid detergent composition.
[0000] Base Member 7
[0043] The dispensing closure 1 according to the present invention comprises as a first essential element, a base member 7 . FIG. 5 shows is a top perspective view of the base member 7 for use in the dispensing closure 1 according to the invention.
[0044] The base member 7 is intended to be mounted onto a container 2 using any suitable means of attachment as indicated above. Suitable means of attachment are designed so as to provide secure sealing between the dispensing closure 1 and the container 2 vis-à-vis its content.
[0045] The base member 7 may have any suitable configuration, form or dimension for accommodating an upwardly projecting neck 5 or portion of a container 2 . A preferred execution of the present invention, wherein the base member 7 has a substantially egg-like shape, preferably an egg-like shape, more preferably an elliptical shape, when seen from the top, as represented in the accompanying drawings.
[0046] The base member 7 is comprised of two distinct parts: a skirt 8 and a platform 9 . The skirt 8 generally forms the lower part of the base member 7 and extends substantially towards the container direction, typically parallel to the neck 5 of the container 2 . Preferably, the skirt 8 has a substantially cylindrical shape, preferably a cylindrical shape. The platform 9 , which typically extends substantially transversely to the longitudinal axis of the container 2 , generally corresponds to the upper part of the base member 7 . In a preferred execution of the present invention, the platform 9 has a substantially flat, plate-like shape and is provided with a platform lip 10 extending substantially over the outer perimeter of said platform 9 . Platform 9 may be substantially horizontal. However, according to a highly preferred embodiment, platform 9 may be adapted such as to have an inclination of between 5 and 45 degrees, preferably between 10 and 40 degrees, more preferably between 20 and 30 degrees, most preferably between 20 and 25 degrees, above a virtual horizontal axis. As shown in FIG. 10 and FIG. 11 , the means for attachment 9 is preferably located onto the inner wall 11 of the skirt 8 .
[0047] Also shown in FIG. 10 and FIG. 11 , the base member 7 further comprises a draining canal 12 adapted to communicate with the interior volume of the container 2 such as to permit dispensing of the container content by the discharging means 13 , via the dispensing opening 3 and the dispensing aperture 18 , when the cap 19 is in its upper position. Said draining canal 12 is typically delimited by the contours of said skirt 8 .
[0048] Discharging means 13 for use herein may be readily recognized and selected by those skilled in the art. Preferably, said discharging means 13 is a pouring spout. In a more preferred execution, the discharging means 13 is a beveled spout which extends upwardly from said base member 7 , preferably from said platform 9 . Such preferred spout allows better control and more precise dispensing of the container content, especially viscous liquids such as liquid detergents. It is preferred that said discharging means 13 has a substantially annular shape.
[0049] In a further preferred embodiment of the present invention, said discharging means 13 is located in such a way as to form spacing between said discharging means 13 and the outer perimeter of said platform 9 . Said spacing may preferably take the form of a circular drainer 14 adapted to recuperate any pourable product contained within the container 2 , preferably viscous liquid product, which would not have been properly dispensed from said discharging means 13 . Also, said spacing is preferably provided with apertures 33 communicating with the interior of the container 2 so as to permit the recuperated product to be drained back into the container 2 . Additionally, said apertures 33 will also constitute air intake means adapted to allow air to penetrate into the container 2 in response to the evacuation of its content and thereby contribute to a better dispensing of the container content, preferably viscous liquids.
[0050] Referring now specifically to FIG. 5 , the base member 7 further comprises a hollow sleeve 15 adapted to communicate with said draining canal 12 . The hollow sleeve 15 shall be adapted so as engage the hereafter-described barrel 21 for axial motion with respect to said hollow sleeve 15 . Suitable hollow sleeve 15 for use herein will be readily apparent to those skilled in the art. However, in a preferred execution, said hollow sleeve 15 has a substantially cylindrical shape, preferably a cylindrical shape, and is provided with an inner 16 and an outer surface 17 . Preferably, said hollow sleeve 15 extends upwardly from said base member 7 , more preferably from said platform 9 , and is open at both ends.
[0051] The hollow sleeve 15 may extend substantially towards the container direction, typically parallel to the neck 5 of the container 2 and therefore towards a substantially vertical axis. In a highly preferred embodiment however, said hollow sleeve 15 may be positioned such as to have an inclination of between 5 and 45 degrees, preferably between 10 and 40 degrees, more preferably between 20 and 30 degrees, most preferably between 20 and 25 degrees, below a virtual vertical axis.
[0052] According to the present invention, said hollow sleeve 15 is provided with a dispensing aperture 18 capable of dispensing the pourable product contained into said container 2 , and positioned such as to communicate with said discharging means 13 .
[0053] The constituting parts of the base member 7 are formed from any suitable material commonly known in the art. Preferably, said parts are all formed from heat sealable thermoplastic materials such as polyethylene or polypropylene single piece. Accordingly, and in a preferred execution of the invention, the base member 7 is a monolithic piece formed from the same thermoplastic material. According to this specific embodiment, the different parts may be advantageously molded within a single injection molding operation which therefore involves both a simple and economical manufacturing process.
[0000] Cap 19
[0054] The dispensing closure 1 according to the present invention is further provided with a cap 19 , the role of which is to cover the discharging means 13 in a tight manner vis-à-vis the content of the container 2 when said cap 19 is in its lower/closed position. FIG. 4 shows a bottom perspective view of said cap 19 .
[0055] The cap 19 for use herein is comprised of two distinct parts: a cap top 20 and a barrel 21 . The cap top 20 generally forms the upper part of the cap 19 and extends substantially transversely to the longitudinal axis of the container 2 . It is typically provided with an inner face 32 and an outer surface 31 .
[0056] The cap top 20 for use herein may however have any suitable configuration, form or dimension for accommodating said platform 9 and said discharging means 13 . Suitable cap tops 20 for use herein will easily be recognized by those skilled in the art. In a preferred execution, the cap 19 has a substantially rounded shape which will allow proper covering of said discharging means 13 . Preferably, the cap 19 has a concave form with the concavity turned towards the direction of the platform 9 . More preferably, the cap top 20 is provided with a substantially egg-like shape, preferably an egg-like shape, more preferably an elliptical shape, when seen from the top, as represented in the accompanying drawings.
[0057] In a highly preferred execution of the present invention, said cap top 20 is further provided with a front screen 24 which is intended to selectively cover the extremity of said discharging means 13 . Typically, said front screen 24 is located at the front part of said cap top 20 .
[0058] The cap top 20 for use herein preferably possesses a cap lip 25 which is typically a substantially annular lip and which extends over the outer perimeter of said cap top 20 . In that preferred embodiment, the cap lip 25 is adapted to tightly conform to the platform lip 10 contours, so as to provide a first sealing means of said cap 19 onto the base member 7 vis-à-vis the content of the container 2 when said cap 19 is in its lower/closed position.
[0059] According to a preferred aspect of the invention, the outer surface 31 of said cap top 20 is further provided with a gripping means 26 , which is preferably a finger grip and which is typically located at the back part of the cap top 20 . Any gripping means commonly known in the art may be used in the context of the present invention. In a very preferred embodiment, the gripping means 26 is especially adapted to provide suitable gripping by pinching with two fingers. The exterior configuration of the cap top 20 for use herein may be varied as desired for aesthetic appearance or for further improved gripping. The latter may be e.g. provided with incrustations, serrations, grooves, indentations or any other operation commonly know in the art.
[0060] As show in FIG. 4 , the cap 19 is further provided with a barrel 21 which generally forms the lower part of the cap 19 . Said barrel 21 typically extends substantially transversely to the plan formed by said cap top 20 .
[0061] The barrel 21 for use herein may however have any suitable configuration, form or dimension for accommodating said discharging means 13 and in particular said hollow sleeve 15 . Suitable barrel 21 for use herein will easily be recognized by those skilled in the art. However, in a preferred execution, said barrel 21 has a substantially cylindrical shape, preferably a cylindrical shape, and is provided with an inner 22 and an outer surface 23 . Preferably, said barrel 21 extends downwardly from said cap top 20 and is open at the end (i.e. lower end) opposite to that facing said cap top 20 (i.e. upper end).
[0062] As previously mentioned, the barrel 21 is adapted so as to be engaged for axial motion with respect to said hollow sleeve 15 . Accordingly, and in a highly preferred embodiment of the present invention, the outer diameter (corresponding to the outer surface 23 ) of said barrel 21 is slightly inferior to the inner diameter (corresponding to the inner surface 16 ) of said hollow sleeve 15 . According to this preferred embodiment, the barrel 21 is allowed to axially slide within the interior of said hollow sleeve 15 , via the hereinafter described complementary means 27 , 28 of raising and lowering the cap 19 , while still providing efficient air tight seal (second sealing means) vis-à-vis the content of the container 2 when said barrel 21 obstructs said dispensing aperture 18 .
[0063] In another highly preferred execution, the lower end of said barrel 21 is provided with a cross section which is non-perpendicular to the longitudinal axis thereof. As represented in FIG. 10 and FIG. 11 , the barrel 21 for use in the present invention is preferably provided with a beveled lower end. According to this highly preferred embodiment, the dispensing aperture 18 may be unobstructed/obstructed with a limited rotation of said cap 19 and thus much faster than with the configuration where the lower end of said barrel 21 in non-beveled.
[0064] The cap 19 for use in the present invention may be formed from any suitable material commonly known in the art. Preferably, said cap 19 is formed as a single piece from heat sealable thermoplastic materials such as polyethylene or polypropylene single piece.
[0000] Complementary Means 27 , 28 of Raising and Lowering the Cap 19
[0065] The dispensing closure 1 according to the present invention further comprises, as another essential technical feature, complementary means 27 , 28 of raising and lowering said cap 19 by rotation thereof.
[0066] Complementary means 27 , 28 for use in the present invention are located in said barrel 21 and in said hollow sleeve 15 , and are adapted for switching said cap 19 from a lower position and an upper position, by rotation of said cap 19 .
[0067] Suitable complementary means 27 , 28 for use herein will easily be recognized by those skilled in the art. Those include but are not limited to angled or helical threads, helical grooves or notches, in combination with complementary helical threads or lugs
[0068] According to a preferred embodiment of the present invention, the complementary means 27 , 28 of raising and lowering said cap 19 by rotation thereof, are a cooperative combination of discontinuous helical grooves 27 and lugs 28 . In a more preferred execution, and as represented in FIG. 4 and FIG. 5 , said helical grooves 27 are located in said hollow sleeve 15 , preferably in the inner surface 16 of said hollow sleeve 15 , and said lugs 28 are positioned in said barrel 21 , preferably in the outer surface 23 of said barrel 21 .
[0069] In the illustrated embodiment, two such helical grooves 27 are provided at an angular increment of 180 degrees. The corresponding two lugs 28 are preferably spaced at 180 degrees increment as well. In a preferred execution, said lugs 28 have a substantially cylindrical shape, preferably a cylindrical shape, to conform to and slide within the corresponding grooves 27 .
[0070] As indicated above, the complementary means 27 , 28 of raising and lowering said cap 19 by rotation thereof, are adapted to switch said cap 19 from a lower/closed position to an upper/open position. According to a highly preferred execution of the present invention, said complementary means 27 , 28 are adapted so as to allow said cap 19 to be switched from said lower position to said upper position through a limited angular displacement, preferably 180 degrees. In a very preferred embodiment, said helical grooves 27 are adapted such as angular displacement of more than 180 degrees is not permitted. This may be achieved e.g. by means of suitable rotation stops 29 , as represented in FIG. 5 .
[0071] In the normal course of a closing/opening operation, while said cap 19 is in its lower/closed position (see FIG. 10 ), the dispensing aperture 18 is obstructed by said barrel 21 and therefore seals the content of the container 2 . Also, while said cap 19 is its lower position, said cap top 20 covers the discharging means 13 which provides a further sealing means for the container content and provides a visual indication that the dispensing container according to the invention is in its closed position.
[0072] While said cap 19 is being engaged in a rotational movement, said complementary means 27 , 28 are working in cooperation so as to progressively raise said cap 19 towards the axis of said hollow sleeve 15 . As the cap 19 is rising, said dispensing aperture 18 is becoming progressively less and less obstructed until it is completely unobstructed. Concurrent to this axial motion, said cap top 20 is progressively uncovering said discharging means 13 .
[0073] When said dispensing aperture 18 is completely unobstructed, the cap 19 has attained its open position, allowing the content of the container 2 to be dispensed through the discharging means 13 via said dispensing aperture 18 .
[0074] In a highly preferred execution of the present invention, said complementary means 27 , 28 and said barrel 21 are adapted and configured so as to allow said cap 19 to be switched from the lower position to the upper position through an angular rotation of preferably 180 degrees.
[0075] In the context of the present invention, it is preferred that said complementary means 27 , 28 are integrally part of the specific elements they are located in. More specifically and according to a highly preferred embodiment, said helical grooves 27 are preferably integrally part of said hollow sleeve 15 and said lugs 28 are preferably integrally part of said barrel 21 .
[0000] Container Closure Assembly
[0076] In another embodiment, the present invention is directed to a container closure assembly, comprising:
(a) a container 2 having a body portion 4 for holding the container content, a lower closed end for supporting the container 2 , an upper end including a means of attachment thereon adapted to receive and affix a dispensing closure for containers; (b) a dispensing closure 1 according to the invention, mounted on the container 2 .
A Method of Dispensing the Content of a Container 2
[0079] The present invention further encompasses a method of dispensing the content of a container 2 comprising the steps of:
(a) providing a container closure assembly according to the invention, wherein said cap 19 is in its lower position; (b) rotating said cap 19 so as to raise said cap 19 to its upper position; (c) pouring the required amount of the container content through said discharging means 13 ; (d) rotating said cap 19 so as to lower said cap 19 back towards its lower position.
[0084] Use of a container closure assembly according to the invention, for dispensing a liquid composition.
[0085] In a further embodiment, the present invention is directed to the use of a closure assembly according to the present invention for dispensing a liquid composition, preferably a liquid detergent composition, most preferably a liquid laundry detergent composition.
[0086] The dimensions and values disclosed herein are not to be understood as being strictly limited to the exact numerical values recited. Instead, unless otherwise specified, each such dimension is intended to mean both the recited value and a functionally equivalent range surrounding that value. For example, a dimension disclosed as “40 mm” is intended to mean “about 40 mm”.
[0087] All documents cited in the Detailed Description of the Invention are, in relevant part, incorporated herein by reference; the citation of any document is not to be construed as an admission that it is prior art with respect to the present invention. To the extent that any meaning or definition of a term in this document conflicts with any meaning or definition of the same term in a document incorporated by reference, the meaning or definition assigned to that term in this document shall govern.
[0088] While particular embodiments of the present invention have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this invention. | The present invention relates to a closure suitable for dispensing pourable product from a container. More specifically, the present invention is directed to a “twist to open” type closure operated by a twisting action. | 1 |
FIELD OF THE INVENTION
The present invention generally relates to a method and to devices used for the polishing of optical fibers, and more particularly relates to a polishing device that contours the end face of both fiber optic connectors and bare fibers.
BACKGROUND OF THE INVENTION
Fiber optic cables are presently used as a transmission media for telecommunications, datacommunications, video, cable television, sensing systems, power and telemetry. In order to extend cable span lengths, link various fiber segments together, and access terminal equipment such as transmitters and receivers, fiber optic connectors are utilized. Fiber optic connections are able to be opened and reconnected multiple times providing flexibility for network routing and access.
Fiber optic connectors are terminated on the end of a optical fiber. A typical connector consists of a cylindrical ferrule in which an optical fiber is centered and mounted. The connector also has interlocking hardware for mating with other components. Two terminated male connectors are mated together using a female coupler in such a manner that their respective ferrules are precisely aligned. Male fiber optic connectors are also aligned with active devices such as photodiodes, lasers and LEDs mounted in female receptacles.
High loss optical connections limit the length of fiber systems. Reflections created at the optical connection can travel back towards the light transmitter can disrupt laser modulation resulting in signal distortion. The goal of all connections are low light loss and minimal back reflection.
The primary, factor affecting the loss and reflective characteristics of a fiber optic connector is the quality and contour of the end face of the optical fiber. This surface must be free of scratches and pits for maximum light transmission from fiber to fiber or active device to fiber. The curvature and angle of the fiber end surface relative to the connector's ferrule must be of a magnitude which insures physical contact and minimal back reflectance.
The final step in the termination of a fiber optic connector onto an optical fiber is the polishing of the fiber end face. Originally, this procedure was manually accomplished. A connector was placed in a polishing fixture so that its ferrule was slightly protruding from the fixture base surface. The fixture was then repetitively moved across an abrasive polishing film which removed fiber material until the desired scratch-free surface was attained. This procedure was time consuming and sensitive to the operator's individual "touch".
Machines have been developed to automate the polishing process. While providing obvious advantages over manual polishing, prior art has significant shortcomings regarding various steps in the polishing process.
Prior art often is dependent upon the fiber optic connector's interlocking hardware for mounting onto the polishing work fixture. This limits the usefulness of a single work fixture for multiple connector styles. Connectors in these fixtures are spring loaded to maintain positive contact with the polishing surface. This increases the time required to insert and remove connectors from the work fixtures.
Increased labor costs have necessitated a reduction in the time required to polish a fiber optic connector. The polishing procedure of prior art involves multiple steps including the polishing of connectors on several types of polishing films. Minimizing these steps can greatly save time in the polishing operation.
Fiber optic connectors currently available have pre-radiussed end faces with minimal dome offsets in order to provide a low reflective and low loss connection. The aggressive polishing techniques of prior art can inadvertently resurface the fiber ferrule face eventually compromising performance.
A significant shortcoming of prior art consists of the sweeping arc motions and circular movements on eccentric axis's used to traverse the connector across the polishing surface. This motion does not maximize contact with the polishing film surface area and therefore minimizes this consumable item's longtime usefulness.
Prior art also uses a single polishing surface. Since a typical polishing procedure requires fiber contact with varying grits of polishing films, a machine with a single polishing surface will require the operator to change these films several times during the complete process.
SUMMARY OF THE INVENTION
Therefore, it is an object of the invention to provide an automated means for contouring fiber and terminated fiber connector end surfaces in order to minimize connector loss and reflectance.
An advantage of the present invention is to provide a work fixture that will accept a wide range of connector types regardless of their interlocking hardware style if they use the same diameter fiber ferrule. The mounting of the connector in the work fixture is only dependent upon the ferrule not the connector hardware. Connect between the fiber end face and the polishing surface is maintained by the weight of the work fixture itself and not spring-loaded mechanisms which need to be adjusted.
Still another advantage of the present invention is that it consists of a plurality of polishing surfaces across which the fiber will traverse. This eliminates the need to change polishing films for each progressively lower polishing film grit required in the process.
A further advantage of the present invention is the linear movement of the fiber end face across the radius of the polishing surfaces. This motion results in faster material removal without comprising the inherently designed pre-raduissed and pre-domed offset of fiber optic connector. Linear and radial movement also maximizes the contact area between the fiber end face and the polishing film. This results in using more surface area of the polishing film and extending the useful life of this costly and consumable item.
An additional advantage of the present invention's linear and radial movement is that this motion removes fiber material faster and minimizes the number of polishing film grits required for a complete polishing process.
It is still another advantage that the present invention is small, lightweight and portable for operation on a benchtop or handheld position. Since the unit can be both AC and battery powered, in can be used in numerous environments.
The present invention also has the advantage of polishing fiber end faces in either a convex/domed shape or at a predetermined angle relative to the axis of the fiber ferrule. This surface contouring capability insures low reflectance connector performance.
An advantage of the present invention is the means to easily exchange the work fixtures required to obtain either convex/domed or angled fiber end faces.
It is an advantage of the present invention to create fiber end face movement across the plurality of polishing surfaces using a lead screw. The lead screw provides smooth and highly controllable motion which minimizes vibrations and traversing hesitations which can cause fiber end face defects such as scratches and chip-outs.
Other advantages of the invention will become apparent upon reading the following detailed description and appended claims, and upon reference to the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
For a more complete understanding of this invention reference should now be had to the embodiments illustrated in greater detail in the accompanying drawings and described below by way of examples of the invention.
FIG. 1 is an exploded view of a preferred embodiment illustrating the base structure and contouring means.
FIG. 2 is an exploded view of the embodiment's frame.
FIG. 3 is an exploded view of the traversing means.
FIG. 4 is an exploded view of the exchangeable positioning means and work fixture means.
FIG. 5 is a side view of a fiber optic connector assembly with a protruding optical fiber.
FIG. 6 is a cross sectional view of the embodiment illustrating the engagement of the work fixture with the contouring means due to traversing means.
FIG. 7 is a cross sectional view of the embodiment illustrating the deformation of the contouring means by the connector assembly.
FIG. 8 is an isometric view of the embodiment illustrating the base structure, contouring means, frame, traversing means, and work fixture.
FIG. 9 is an exploded view of another embodiment of positioning means.
FIG. 10 is a cross sectional view of the embodiment of FIG. 9 illustrating the engagement of the work fixture with the contouring means due to traversing means.
FIG. 11 is a cross sectional view of the embodiment of FIG. 9 illustrating the deformation of the contouring means by the connector assembly.
While the invention will be described in connection with a preferred embodiment, it will be understood that it is not intended to limit the invention to that embodiment. On the contrary, it is intended to cover all alternatives, modifications and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to FIG. 1, apparatus 1 is provided with a base structure 20. Base structure 20 is provided with two through holes 22 and 24. The inner diameter of through holes 22 and 24 are such that they accommodate the outer diameter of electric motors 26 and 28. Motors 26 and 28 arc secured in through holes 22 and 24. This is preferably accomplished with set screws 46 and 48 which make contact with motors 26 and 28 utilizing threaded through holes 50 and 52 in base structure 20. Motors 26 and 28 arc energized by conventional power supplies (not shown). Suitable power supplies include DC batteries and AC adapters.
Contouring means 33 and 35 are provided with rotary disks 34 and 36, respectively. Rotary disks 34 and 36 are made of materials such as aluminum, stainless steel, synthetic rubber or polymer plastics such as Delrin. Polymer plastics are preferred. Rotary disks 34 and 36 have diameters of approximately 1 to 12 inches. Rotary disks 34 and 36 have a blind drill bole 38 and 40, respectively. Drill holes 38 and 40 have an inner diameter large enough to permit rotary disks 34 and 36 to be mounted upon motor shafts 30 and 32. Rotary disks 34 and 36 can be mounted to motor shafts 30 and 32 by set screws or press fitting. Press fitting is preferred.
Two contouring surfaces 43 and 45 are bonded to rotary disks 34 and 36, respectively. Suitable bonding techniques are adhesives or surface cohesion. Surface cohesive means is preferred. Suitable materials for contouring surfaces 43 and 45 are materials such as natural and synthetic rubber, glass, polymer plastics and metals. Synthetic rubber is preferred. Polishing films 42 and 44 are bound to rotary disks 34 and 36 by means such as adhesives or liquid cohesion. Liquid cohesion is preferred. Polishing films 42 and 44 have a diameter of approximately the diameter of contouring surfaces 43 and 45. Polishing films 42 and 44 consist of bonded, fine grain polishing media made of substances such as SiC, Al2O3, diamond or the like. A suspended colloidal slurry of these aforementioned polishing media may also be present on the polishing films.
Base structure 20 is provided with a notch 21. Base structure 20 is also provided with two through holes 56 and 58 which exit in the cavity formed by notch 21. Through hole 56 has an inner diameter of sufficient size to accept an electric motor 60. Electric motor 60 is mounted in through hole 56 by means such as epoxy, set screws or press fitting. Press fitting is preferred. Electric motor 60 is energized by a conventional power supply (not shown). Suitable power supplies include DC batteries and AC adapters.
Through hole 58 has an inner diameter sufficient in size to accept a roller bearing 64. A conventional roller bearing, such as the roller bearing described on page 1522 of catalog No. 100 of the McMaster-Carr Supply Company, is preferred. Roller bearing 64 is mounted in through hole 58 by means such as epoxy set screws or press fitting. Press fitting is preferred.
One end of a lead screw 66 is engaged with roller bearing 64 by epoxy, set screws, threading or press fitting. Press fitting is preferred. Lead screw 66 has a size of 0.063 inch to 0.5 inch and a pitch of 5 threads per inch to 300 threads per inch.
A nut assembly 68 is threaded along the axis of lead screw 66. The other end of lead screw 66 is engaged with a motor shaft 62 of electric motor 60 with a coupling means 70. Coupling means 70 is preferably a tubular rubber sleeve. Electric motor shaft 62 and the end of lead screw 66 arc engaged with coupling means 70 by press fitting. Other suitable materials for coupling means 70 are rubber, stainless steel, aluminum, brass or copper. Other suitable engagement means between coupling means 70 and lead screw 66 and motor shaft 62 are set screws and locking collars.
Nut assembly 68 has a radial threaded drill hole 72 on surface of its circumference. The inner diameter of drill hole 72 is of sufficient size to accept a coupling pin 76 Coupling pin 76 has a diameter of 0.0313 inch to 0.25 inch and a length of 1 inch to 4 inches. Suitable materials for coupling pin 76 are brass, aluminum or stainless steel. Brass is preferred. Coupling pin 76 is inserted in drill hole 72 to a depth of approximately 0.063 inches to 0.5 inches.
The top surface of base structure 20 is also formed with two threaded drill holes 78 and 80.
Referring next to FIG. 2, apparatus 1 is provided with a frame 82. Suitable materials apparatus frame 82 are aluminum or polymer plastics such as Delrin. Polymer plastics are preferred. The top surface of frame 82 is formed with two through holes 88 and 90 which are respectively positioned for alignment with threaded drill holes 78 and 80 of base structure 20. Two set screws 84 and 86 secure base structure 20 to frame 83 by means of through holes 88 and 90 and threaded drill holes 78 and 80.
Frame 82 is also formed with two through holes 92 and 94 each having an inner diameter greater than the outer diameter of electric motors 26 and 28. Through holes 92 and 94 are positioned to accept electric motors 26 and 28, respectively.
The top surface of frame 82 is also formed with a elongated cutout 96. The length of cutout 96 is equal to or exceeds the combined diameters of rotary disks 34 and 36. Cutout 96 having a width of approximately 0.125 inch to 2 inch is preferred. Cutout 96 is oriented on the surface of frame 82 to permit coupling pin 76 to protrude above the top surface of frame 82 and to traverse along the longitudinal length of cutout 96 without obstruction. The top surface of frame 82 is also formed with two through holes 98 and 100.
Referring to FIG. 3, apparatus 1 is provided with a linear translation slide 102 disposed on frame 82. Linear translation slide 102 consists of a slide base 104 and sliding member 106. Low friction and linearly translational movement is exhibited between slide base 104 and sliding member 106. Slide base 104 is provided with two through holes 108 and 110. Sliding member 106 is provided with four threaded drill holes 130, 132, 134 and 136. The aforedescribed conventional linear translation slide 102 most suitable for use in the present apparatus is found on page 1540 of catalog No. 100 of the McMaster-Carr Supply Company having a part number of 6203K53.
The through holes 108 and 110 of slide base 104 are aligned with through holes 98 and 100 of frame 82. Slide base 104 is preferably affixed to frame 82 by set screws 112 and 114 and fastened with lock nuts 116 and 118.
Apparatus 1 is also provided with a traversing means 120. Suitable materials for traversing means 120 are aluminum, stainless steel or polymer plastics such as Delrin. Delrin is preferred. Traversing means 120 is formed with four through holes 122, 124, 126 and 128 positioned as to obtain alignment with threaded drill holes 130, 132, 134 and 136 in sliding member 106. Traversing means 120 is preferably affixed to slide member 106 with four screws 138, 140, 142 and 144.
The bottom surface of traversing means 120 is also formed with a drill hole 146 having an inner diameter large enough to accept coupling pin 76. Lead screw nut assembly 68 engages with traversing means 120 by means of coupling pin 76 set in drill hole 146.
The top surface of traversing means 120 is also formed with two holes 148 and 150. Two bushings 152 and 154 having an outer diameter equal to or smaller than the inner diameters of holes 148 and 150 and are secured in drill holes 148 and 150 preferably by press fitting. Other suitable means of securing are epoxy or set screws. Suitable materials for bushings 152 and 154 are bronze, stainless steal, nylon or ceramic. Bronze is preferred.
Referring to FIG. 4, apparatus 1 is provided with an exchangeable positioning means 156. Suitable materials for positioning means 156 are aluminum, stainless steel and polymer plastics such as Delrin. Delrin is preferred. The bottom surface of positioning means 156 is formed with two drill holes 158 and 160. Two rear guide pins 162 and 164 are preferably press fitted into drill holes 158 and 160, respectively. The length of rear guide pins 162 and 164 arc such that they extend approximately 0.5 inch to 3 inch beyond the bottom surface of positioning means 156. Suitable materials for rear guide pins 162 and 164 are aluminum, stainless steel, brass or copper. Stainless steel is preferred.
The bottom of positioning means 156 is also provided with a drill hole 170. Drill hole 170 is laterally positioned between drill holes 158 and 160 and located at a distance from drill holes 158 and 160 which is greater than the width of traversing means 120. A front guide pin 172 is preferably press fitted into drill hole 170. The length of front guide pin 172 is such that it extends approximately 0.5 inch to 3 inch beyond the bottom surface of positioning means 156. Suitable materials for front guide pin 172 are aluminum, stainless steel, brass or copper. Stainless steel is preferred. Positioning means 156 is also provided with a threaded drill hole 174. Drill hole 174 is positioned 0.25 inch to 5 inch from front guide pin 172.
The apparatus is provided with an exchangeable work fixture means 176 consisting of an insert 178 held by a lock collar 182. Conventional lock collars such as those described on page 1527 of catalog 100 of the McMaster-Carr Supply Company having a part number of 6435K36 are suitable for lock collar 182. Lock collar 182 is closed by means of screw 184. Lock collar 182 is provide with a through hole 186 which is parallel with the center axis of lock collar 182. A screw 188 inserted into through hole 186. Screw 188 secures work fixture means 176 to the bottom surface of positioning means 156 by engaging with threaded drill hole 174.
Suitable materials for insert 178 are nylon, Delran, polymer plastics, Teflon, stainless steel and aluminum. FEP Teflon is preferred. The thickness of insert 178 is equal to or less then the length of a ferrule 210 of a fiber connector 206. Insert 178 is provided with a plurality of through holes 180 and 181. The diameters of through holes 180 and 181 are sufficient to permit a press fit insertion of ferrule 210.
The operation of the apparatus 1 will now be described. Referring to FIG. 5, a fiber optic connector assembly 206 is positioned upon an optical cable 21. An optical fiber 216 is either flush with a ferrule surface 212 of fiber ferrule 210 or protrudes above ferrule surface 212 of fiber ferrule 210 by approximately 1 micron to 2000 micron. Optical fiber 216 can either be free floating in connector assembly 206 or affixed in connector assembly 206 via epoxy, adhesive bonding, or crimp.
Referring now to FIG. 6, fiber ferrule 210 of connector assembly 206 is press fit into through hole 180 of insert 178. Positioning means 156 is positioned upon traversing means 120. Alignment is accomplished by inserting front guide pin 172 into bushing 154. Rear guide pins 162 and 164 make sliding contact with the rear surface of traversing means 120 to prevent rotation of positioning means 156.
Referring now to FIG. 7, during initial commencement of apparatus 1 operation, the front surface of optical fiber 216 makes contact with the center of polishing film 42 which is rotating about its center axis due its engagement which electric motor 26. Upon contact, optical fiber 216 deforms the surface of polishing film 42 and contouring surface 43. Deformation means can be accomplished by at least two forces. In the case of an adhesivelly mounted connector assembly 206, deformation means is the physical weight of positioning means 156. In the case of a free floating fiber 216 within connector assembly 206, an external deformation means such as pressure exhorted by an operator's hand upon the optical cable 210 is preferred. The amount of deformation is determined by the durameter of contouring surface 43. The durameter of contouring surface 43 is preferably of a degree such that as material of optical fiber 216 is removed during the polishing process, its end surface face obtains a convex shape which matches the curvature of the ferrule surface 212.
Referring to FIG. 8, traversing means 120 is connected to nut assembly 68 by coupling pin 76. When electric motor 60 is engaged, it rotates lead screw 66 which is terminated in roller bearing 64. This motion causes nut assembly 68 to traverse along lead screw 66 which in turn causes traversing means 120 to move along the length of linear translation slide 102 in the same direction. As traversing means 120 moves along translation slide 102, connector assembly 206 radially travels across polishing film 42 which removes material from the end face of optical fiber 216 in a uniform fashion. This motion across polishing film 42 insures maximum utilization and uniform wearing of the surface area of polishing film 42.
Once connector assembly 206 approaches the circumference of polishing film 42, the operation of electric motor 60 is ceased. Positioning means 156 is removed from bushing 154 of traversing means 120 and front guide pin 172 is now located in bushing 152. This repositioning of positioning means 156 in traversing means 120 aligns connector assembly 206 in the center of polishing film 44. Polishing film 44 has a finer grain size relative to polishing film 42.
Electric motor 60 is once again engaged initiating the linear movement of connector assembly 206 across polishing film 44 which is rotating. As connector assembly 206 moves, the fine grain of polishing film 44 removes any fine scratches, pits and imperfections on the end face of optical fiber 216. When connector assembly 206 reaches the perimeter of polishing film 44 the operation of apparatus 1 is complete.
In another embodiment of the present invention, apparatus 2 of FIG. 9, is shown having another embodiment of a positioning means 156A. The remaining elements of apparatus 2 are the same as those in apparatus 1 and therefore, such common elements are represented by the same Arabic numerals.
Suitable materials for positioning means 156A are aluminum, stainless steel and polymer plastics such as Delrin. The bottom surface of positioning means 156A is formed with two drill holes 158A and 160A. Drill holes 158A and 160A are formed at an angle x relative to the center axis of positioning means 156A. The degree of this angle x is between 0.5° and 25°, preferably 8°.
Two rear guide pins 162A and 164A are preferably press fitted into drill holes 158A and 160A. The length of rear guide pins 162A and 164A are such that they extend approximately 1/2 inch to 3 inch beyond the bottom surface of positioning means 156A.
The bottom of positioning means 156A is also provided with a drill hole 170A. Drill hole 170A is laterally positioned between drill holes 158A and 160A and located at a distance from drill holes 158A and 160A greater than the width of traversing means 120 of FIG. 3. Drill hole 170A is formed at an angle x relative to the center axis of positioning means 156A. The degree of this angle x is between 0.5° and 25°, preferably 8°. A front guide pin 172A is preferably press fitted into drill hole 170A. The length of front guide pin 172A is such that extends approximately 1/2 inch to 3 inch beyond the bottom surface of positioning means 156A.
The bottom of positioning means 156A is also provided with a threaded drill hole 174A. Threaded drill hole 174A is formed parallel with the center axis of positioning means 156A. Threaded drill hole 174A is of a diameter that will accept set screw 188 which secures work fixture means 176 of FIG. 4 to the bottom of positioning means 156A.
Referring now to FIG. 10, the operation of apparatus 2 will be described. Fiber ferrule 210 of connector assembly 206 is press fit into through hole 180 of insert 178. Positioning means 156A is positioned upon traversing means 120. Alignment means are accomplished by inserting front guide pin 172A into bushing 154. Rear guide pins 162A and 164A make contact with the rear surface of traversing means 120 to prevent rotation of positioning means 156A.
During initial commencement of apparatus 2 operation, optical fiber 216 which is protruding from ferrule end face 212, makes contact with the center of polishing film 42 which is rotating about its center axis due its engagement which electric motor 26. Optical fiber 216 makes contact with the surface of polishing film 42 at an angle equal to the previously described angle x formed between drill hole 170A and the center axis of positioning means 156A, as illustrated in FIG. 11.
Upon contact, optical fiber 216 deforms the surface of polishing film 42 and contouring surface 43 as displayed in FIG. 11. Deformation means can be accomplished by at least two forces. In the case of an adhesivelly mounted connector assembly 206, deformation means is the physical weight of positioning means 156A. In the case of a free floating fiber 216 within connector assembly 206, an external deformation means such as pressure exhorted by an operator's hand upon the optical cable 210 is preferred. The amount of deformation is determined by the durameter of contouring surface 43. As material of optical fiber 216 is removed during the polishing process, the plane in which the end surface of optical fiber 216 lies is at an angle relative to the center axis of ferrule 210 equal to the previously described angle formed between drill hole 170A and the center axis of positioning means 156A. | An apparatus for polishing the end faces of bare optical fibers or connector terminated fibers so that their shape is either convex or angled. The base structure of the apparatus utilizes several rotating disks upon which deformable pads are mounted. Attached to each pad are polishing films with progressively finer grades of abrasive action. A connector ferrule containing a protruding fiber is mounted in an exchangeable work fixture. Depending upon the selected work fixture, the fiber face is pressed against the coarsest rotating polishing film at a predetermined angle. A carriage linearly traverses the work fixture across the radius of the polishing film resulting in the removal of fiber end face material. Once the circumference of the film is reached the work fixture is repositioned so that radial movement can commence across the adjacent finer grade polishing film. | 1 |
FIELD OF THE INVENTION
The invention relates generally to multi-ribbed power transmission belts having a cog design and sequence intended to minimize noise while in operation and, more particularly, to the manufacture of such belts in varying sizes.
BACKGROUND OF THE INVENTION
Power transmission belts having a variety of groove and rib configurations are known. One such belt is a multi-ribbed belt. The multi-ribbed belts have a tension section, a load carrying section, and a compression section. Multi-ribbed belts may also be provided with transverse grooves; such transverse grooves extending either traverse to the belt or at an angle relative to the traverse direction of the belt. The longitudinal and transverse grooves are located in the compression section. Such belts are known as cogged multi-ribbed belts, examples of which are disclosed in U.S. Pat. Nos. 4,002,082 and 5,382,198. Cogged multi-ribbed belts exhibit improved flexibility and longer life.
However, cogged multi-ribbed belts create more noise due to a non-continuous rib entering and exiting the grooved pulley. Noise is generated when the tooth travels and presses into the pulley groove, compressing and displacing the air in the groove and noise is generated when the tooth exits the pulley groove as air rushes to fill the now empty pulley groove. Furthermore, there are harmonic noise spikes generated by the cogs at the cog engagement frequency.
Two methods are known to reduce the noise of a cogged multi-ribbed belt. The first is to incline the transverse grooves at an angle relative to the transverse direction. This reduces the overall noise level but the harmonic noise spikes are often still objectionable.
The second is to vary the pitch of the cogs with a repeating pitch pattern, as disclosed by U.S. Pat. Nos. 4,262,314 and 4,832,670. U.S. Pat. No. 4,262,314 discloses a cog belt with reduced noise. The transverse groove depths, the groove angles, and the distance between the grooves are varied. Similar to U.S. Pat. No. 4,262,314, U.S. Pat. No. 4,832,670 also discloses multiple elements of the belt construction are varied simultaneously to produce a reduced noise belt. The belt is defined by a repeating sequence pattern along the length of the belt. An ideal pitch pattern that results in a minimization of noise, however, needs to vary based on the circumferential length of the belt. Thus, to optimize reduction of noise in belts of varying length, each belt would require a unique respective pitch sequence or pattern.
The manufacture of a cogged, multi-ribbed belt may be effected in a plurality of processes common to the industry. U.S. Pat. Nos. 4,575,445 and 4,512,834 illustrate and describe two such manufacturing processes and are representative of the manufacture of a cogged belt from one or more molds. A third alternative process begins with a metal preform board. The cog profile is machined into the board and a rubber matrix is made from the preform board. This matrix is then spliced on the outside of green diaphragm rubber to form a diaphragm mold. The diaphragm molds hence have an external cog profile identical to the actual belt and the rubber diaphragm molds are then used to make diaphragms. Belt materials are plied on a build mandrel and dropped into a diaphragm in a cure pot. After a slab of the belts have been formed and cured, “v's” are milled and slit into individual belts. The three processes referenced above are not exclusive and other cogged belt manufacturing methods are known and utilized in the industry. Common to numerous known approaches is that one or more molds are used for the purpose of creating the cog sequence in a belt. For belts having a repeating or random cog sequence, the molds used in the manufacture thereof must mirror the desired cog profile and pattern.
From the foregoing, it will be appreciated that the creation of one or more molds for the purpose of manufacturing a cogged belt, by any of the processes known and practiced in the industry is an investment of capital and, hence, expensive. Since a mold is cog-profile specific, that is, identical to the cog profile desired in the actual belt, belts having cogs of differing profiles or pitch sequencing are typically formed from a mold unique to the belt.
As mentioned above, it is often desirable to utilize a repeating pitch pattern to reduce the noise generated from a cogged multi-ribbed belt. However, the ideal pitch pattern on a belt needs to vary based on the circumferential length of the belt. Heretofore, in order to manufacture a belt of a given circumferential length, a unique, dedicated mold providing the requisite optimized pitch sequence was required. Because the creation of a unique mold for each length of belt is cost prohibitive, the industry practice has been to been slow to adopt noise reduction techniques in cog design and sequence in belts of varying length. While this practice avoids the costly proliferation of unique, belt-length dependent, manufacturing molds, optimized noise reduction is sacrificed.
SUMMARY OF THE INVENTION
The present invention is directed to the economical and optimized manufacture of a power transmission belt of a type known in the industry. Such belts typically have an inner surface comprising longitudinally extending grooves and transverse grooves. The transverse grooves may be inclined at an angle (for example, less than 90°) relative to the longitudinal direction of the belt and all the transverse grooves may have the same or a mutually differentiated groove depth. The transverse and longitudinal grooves form transverse rows of cogs on the belt inner surface. The rows of cogs may have different longitudinal lengths, and the rows may be randomly arranged along the entire length of the belt. The pitch lengths of the rows of cogs are randomized or sequenced over the entire length of the belt to reduce the noise of the belt as it travels about its associated pulleys. The ideal pitch pattern on a belt is variable, dependent upon the circumferential length of the belt.
Pursuant to one aspect of the invention, to create an optimized pitch sequence for at least two belts of differing lengths, a method of manufacture is employed wherein a the optimized pitch sequence of the shorter belt is incorporated into the optimized pitch sequence of the longer belt. A single mold may thus be employed in the manufacture of either belt. The longer belt may contain cogs of various shapes intended to offset a range of frequencies and minimize noise generation. By selecting a certain pitch sequence span along the mold for the longer belt, the shorter belt may be manufactured from the same mold and the noise characteristics of the smaller belt may be controlled and optimized. Tooling costs are minimized and noise reduction is facilitated without the costly proliferation of molds for belts of differing lengths.
In another aspect of the invention, the optimized pitch sequence for two or more belts of differing lengths are incorporated into the optimized pitch sequence of a longer third belt. Different spans along a single mold for the longest belt may be selected and utilized, to the exclusion of unselected other spans along the mold, in the manufacture of the smaller belts. The noise characteristics of the smaller belts may thus be controlled and optimized using the same mold that is used in the formation of longer belts.
The subject invention is described in a preferred embodiment below and illustrated in the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be described by way of example and with reference to the accompanying drawings in which:
FIG. 1 is a bottom plan view of a section of the belt of this invention;
FIG. 2 is an enlarged view of the belt taken along the line 2 — 2 in FIG. 1 ;
FIG. 3 is a diagrammatic representation of belts of various lengths and their manufacture pursuant to the invention from a single mold.
DETAILED DESCRIPTION OF THE INVENTION
A multi-ribbed power transmission belt 10 of a type commercially available in the industry is shown in FIGS. 1 and 2 . Belts such as belt 10 may be formed in various lengths, each belt having an optimized pitch sequence pursuant to the invention. Other belt configurations may also utilized the teachings of the invention. Belt 10 is one of many belt configurations that may be produced has a tension section 12 , a load carrying section 14 , and a compression section 16 . The compression section has a plurality of longitudinal ribs 18 formed by parallel longitudinal grooves 19 and a plurality of parallel transverse grooves 20 . The transverse grooves 20 are oriented at an angle α other than perpendicular to the longitudinal direction L. The combination of longitudinal grooves 19 and transverse grooves 20 form a plurality of cogs 21 on the belt surface, with a transverse cog row 22 being defined between adjacent transverse grooves 20 .
The angle α of the transverse grooves 20 is from 20° to 85°. While the number of ribs shown in the drawings is six, it should be appreciated that a multi-ribbed transmission belt may contain anywhere from three upwards to thirty or more. The grooves 20 may be U shaped, V shaped, or V shaped with a rounded bottom or any other convenient shape. The depth c of all the transverse grooves 20 are the same and the depth r of all the longitudinal grooves 19 ; however, the depth c of the transverse grooves 20 can be the same or different from the depth r of the longitudinal grooves 19 . Alternatively, the depth can vary from transverse groove to transverse groove if desired. The depth r of the longitudinal grooves 19 is generally greater than the depth c of the transverse grooves 20 but not so deep as to cut into the longitudinal reinforcing cords 24 .
Each transverse cog row 22 has a longitudinal length P extending from a location on the cog 21 to the identical location on the longitudinally adjacent cog 21 ; the determining location, as seen in FIG. 1 , is best selected to be a corner edge adjacent to the transverse groove 20 . In accordance with the invention, the longitudinal length P of adjacent cog rows 22 may not have the same length P. In the illustrated belt, the belt has three discrete different longitudinal lengths, P 1 , P 2 , and P 3 .
Typical normalized length ratios of lengths of the small, medium and large lengths useful in the belt 10 include 9-10-11, 11-13-15, 5-6-7, 9-11-13, 7-9-11, 9-10-12, 6-7-9, and 4-7-10. While these ratios are only for three differing normalized longitudinal lengths, it is possible to utilize three to six different longitudinal lengths. The total number of longitudinal lengths, P n , for a particular belt would be limited by the belt size and the complexity of the mold required to form the belt.
Because the multi-ribbed belt 10 is driven about its associated grooved pulleys due to the friction interaction between the pulley grooves and the sides of the longitudinal ribs 18 , the sequencing of the different longitudinal lengths P 1 , P 2 , P 3 need not be limited to a repeating defined period. The longitudinal lengths along the entire length of the belt may be randomized.
One exemplary sequencing pattern for a belt, using three discrete pitch lengths is:
3 3 3 2 1 2 3 2 3 2 1 1 2 1 1 2 1 2 3 1 3 3 1 2 2 2 1 3 1 2 1 3 1 1 1 2 3 3 2 2 2 3 2 1 1 3 3 3 2 1 2 3 2 3 3 2 1 2 2 1 1 3 2 1 2 3 1 1 3 1 2 3 2 1 1 3 1 2 2 3 3 3 1 1 3 3 2 3 1 1 1 2 2 3 2 1 1 2 1 3 3 2 3 3 3 2 2 3 3 1 1 3 2 1 2 2 1 1 3 2 2 3 3 3 1 2 2 1 1 1 2 3 2 3 1 1 1 2 1 2 2 3 3 1 1 3 2 1 3 3 2 3 1 3 3 2 3 2 1 2 3 1 3 1 1 2 1 2 1 2 3 3 2 3 3 3 1 1 2 1 2 3 2 2 2 2 3 3 2 1 1 3 2 3 2 3 1 2 2 1 2 1 3 1 1 1 1 3 2 1 2 1 3 3 2 3 2 1 2 1 2 3 2 1 2 2 3 1 1 1 3 1 3 1 3 2 3 3 2 1 1 2 3 1 2 2 3 2 3 3 3.
The only limitation in sequencing of the pitch lengths is a limitation on the number of adjacent similar pitch lengths. If too many cogs rows 22 having an identical pitch length are adjacent, then the desired reduction in noise may not be achieved. Additionally, if too many cog rows 22 having a small pitch length are adjacent, durability issues may arise. No more than six, preferably four, identical longitudinal length cog rows 22 should be adjacent to one another.
To determine the actual longitudinal length of the cog rows 22 , the following equation is used:
((length ratio number)*(belt length))/(total normalized length for sequence).
For example, using the sequence listed above and the ratio combination of 4-7-10, the total normalized length for the sequence is 1760. The total normalized length is achieved by substituting the ratio length number (i.e., 4, 7, or 10) for the sequence length (i.e. 1, 2, or 3) and than adding up the length numbers for the entire sequence. For a belt length of 222.60 cm (87.6 inches), and using the sequence above, the longitudinal lengths are:
small length P 1 : (4*222.6)/1760=0.506 cm medium length P 2 : (7*222.6)/1760=0.885 cm large length P 3 : (10*222.6)/1760=1.265 cm.
A second pitch sequence using three pitch lengths is:
2 1 1 1 1 3 2 1 2 3 1 2 2 1 1 3 2 3 2 1 2 1 3 2 3 2 3 3 1 3 3 2 2 2 1 1 2 1 2 2 3 1 3 3 2 1 3 1 2 1 1 3 1 1 3 2 1 1 1 3 1 2 3 3 3 1 3 2 1 3 3 3 2 3 3 1 2 2 3 3 3 1 2 2 1 2 1 2 1 2 2 2 1 3 3 2 3 1 1 3 3 1 2 2 1 1 3 2 2 2 1 2 2 1 3 1 3 3 1 1 3 3 1 2 2 3 1 3 1 1 1 3 3 1 2 1 2 1 1 2 3 2 3 3 2 2 3 2 1 2 3 2 1 1 1 3 3 2 2 3 2 1 1 2 1 3 2 2 3 3 3 3 2 1 1 3 1 1 2 3 2 2 3 3 3 2 1 2 1 2 2 1 3 2 1 1 1 2 1 3 3 1 2 2 3 1 2 3 3 2 2 1 1 2 3 3 2 1 1 2 3 3 3 2 3 3 3 2 1 3 1 2 1 3 3 2 3 1 1 2 1 1 2 2 2 3 3 1 2 2 1 1 2 3 1 3 3 3 2 3 3 1 2 1 1 1 3 2 2 2 1 1 2 3 1 3 3 2 1 3 3 2 1 2 3 3 2
For this second pitch sequence, using a ratio combination of 4-7-10, the normalized length is 2016. For a belt length of 2560 mm, the longitudinal lengths are:
small length P 1 : (4*256.0)/2016=0.508 cm medium length P 2 : (7*256.0)/2016=0.888 cm large length P 3 : (10*256.0)/2016=1.270 cm
The belt of this invention is illustrated in the drawings as being elastomeric. The elastomers may be any one of those known to be suitable for use In such belts, e.g., polychloroprene, polyurethane, NBR, IIR, IR, SBR, CSM, EPDM, other thermosets, thermoplastic elastomers and other polymer alloys.
The load carrying section 14 of this belt can be made of any suitable material and used in any suitable technique known in the art. Preferably, the load carrying section 14 is made of a helically wound load carrying cord 24 having individual turns thereof arranged in substantially equally spaced relation across the belt body. These cords may be made from glass fibers, aramid fibers, carbon fibers, steel, polyester, high tenacity rayon, or polyaramide.
The preferred method of manufacturing the belt of this invention is to build the belt inverted on a rigid mandrel of the proper diameter. A layer of tension stock is first applied to the mandrel followed by the helical windings of the reinforcing cord 24 . Then a layer of cushion stock is applied over the reinforcing cord 24 . The angular grooves 20 are molded into the product at the time of cure by means of a flexible diaphragm having the helical pattern opposite that of the grooves placed around the cushion stock and compressed against the product by steam pressure, air pressure, or other means. Following the curing process, the longitudinal grooves are then formed in the conventional manner by machining, grinding, etc.
By pitching the cogged belt 10 in the manner disclosed in the present invention, the noise spikes at the harmonic frequency are reduced as well as the overall noise of the belt 10 . As described previously, the optimum pitch sequence for a belt is dependent upon the length of the belt. Belts of various lengths, accordingly, will have a mutually exclusive optimal pitch sequence. The use of a dedicated mold for the production of each size belt in order to optimize its pitch sequence, however, is cost prohibited. Pursuant to the present invention, therefore, a pitch sequence that will minimize noise in a smaller belt or smaller belts is selected from the pitch sequence of the longest belt. For example, with reference to FIG. 3 there are shown line diagrams for belts of various size (length). The belt lengths indicated are solely for the purpose of illustration, it being understood that the subject invention will apply to belts of other sizes.
In FIG. 3 , identification of belts of differing lengths is made along the y-axis. Represented belt lengths are, in order of diminishing length, 3620 mm; 2560 mm; 2525 mm; 2515 mm; and 2115 mm. The x-axis is scaled to reflect the length of each belt, with the longest belt 26 (3620 mm) referenced as a horizontal line beginning at the zero point on the x-axis and extending for 3620 mm. The remaining belts are represented as horizontal lines 28 , 30 , 32 , and 34 , respectively, each beginning at a respective reference point 36 on the graph and extending to a terminal point 38 .
It will be appreciated that, pursuant to the invention, the longest belt 26 is formed from a mold. The process for forming a belt may be any one of several common in the industry. In the process described previously, the manufacture of a belt begins with a metal preform board. The cog profile is machined into the board and a rubber matrix is made from the preform board. This matrix is then spliced on the outside of diaphragm rubber to form a diaphragm mold. The diaphragm molds hence have an external cog profile identical to the actual belt and the rubber diaphragm molds are then used to make diaphragms. Belt materials are plied on a build mandrel and dropped into a diaphragm in a cure pot. After a slab of the belts have been formed and cured, “v's” are milled and slit into individual belts.
As used herein, “N(total)” represents the total number of cogs on the matrix board. In the example represented in FIG. 3 , N(total) is 405. Thus, for the longest belt 26 , all of the cogs on the matrix board are used to form the longest green belt, that is 405 cogs. While it is preferred that N(total) for the matrix board equate with the number of cogs necessary to create the longest belt, such is not mandatory. The longest belt 26 may, if desired, be formed from a mold having a greater number of cogs than necessary for the creation of belt 26 . For economic reasons, however, it is preferred that the number of cogs in the mold not exceed the number of cogs necessary to produce the longest belt size. “N”, as referred to in FIG. 3 , represents the total number of cogs from the matrix board necessary to create a green belt for each specific belt length. “n” represents the number of cogs not used on the matrix board to form a give green belt length. The “n” value to the left side of the line representing each size of green belt represents the number of unused cogs to the left of the belt; the “n” value to the right representing the number of unused cogs to the right.
FIG. 3 illustrates that the invention uses one long mold with a given pitch sequence for forming the longest belt 26 . Smaller belts are formed from spans of this long pitch sequence, each span beginning at a unique initiation point 36 and terminating at a unique terminal end point 38 . The pitch sequence within each span 38 , 30 , 32 , and 34 will therefore be unique and function to optimize the noise reduction for the particular belt size. The initiation points 36 will vary from belt size to belt size as well. For example, the 2560 belt span begins at a point 36 in which 117 cogs are unused to the left. Belt span 2545 , however, has an initiation point 36 in which only 28 unused cogs remain to the left. The pitch sequence within each span 38 , 30 , 32 , and 34 will accordingly be unique for each size belts but all sizes of belts may be formed from the pitch sequence comprising the longest belt 26 .
The number of cogs in each belt span (“N”) will likewise vary from belt to belt. The “N” value for belt 2560 is 288 cogs while the “N” value for belt 2545 is 285. Likewise the terminal points 38 may vary from belt size to belt size as well, depending on where the pitch sequence on the matrix board should end so as to optimize noise reduction for that size belt. For example, the terminal points 38 for belts 2115 and 2515 leaves n=50 cogs unused to the right, while the terminal point for belt 2545 leaves n=92 unused cogs to the right. For the 3620 mm belt, the n value is zero for both the left and right sides since it uses the entire matrix board.
It will be appreciated that N=N(total)−(n left+n right). The method of manufacture comprises the steps: making a mold for a long belt size that incorporates within the mold at least one pitch sequence optimal for reducing noise for a smaller belt size. An impression is made in the rubber and an optimal pitch sequence span is selected for the particular belt size desired. The selected optimal span is severed from the rest of the rubber and the unselected portions are discarded or reused.
While ideally it is preferable to incorporate, or integrate, a pitch sequence that minimizes the noise in the shorter belt(s) into the pitch sequence of the longer belt, such is not required to practice the subject invention. The long pitch sequence necessary to minimize the noise generated by the longer belt may not necessarily include a pitch sequence span necessary to reduce noise generation in the shorter belt to an absolute low. A compromise, however, may be attainable wherein a pitch sequence span in the longer pitch sequence may achieve an adequate noise reduction in the shorter belt even though an ideal pitch sequence in a separate mold may provide a further marginal reduction. The marginal improvement in noise reduction achievable by the ideal pitch sequence may not, however, be significant enough to warrant the creation of a separate mold for the shorter belt. A tradeoff in the noise reduction of the shorter pitch sequence span may be necessary and acceptable in exchange for eliminating the need for and expense of a separate mold. Use of the term “optimization”, therefore, does not necessarily mean an absolute reduction of noise level generated by a belt. Rather, “optimization” as used herein means a relative reduction in noise to an acceptably low level while preserving the flexibility of using a single mold in the manufacture of belts of two or more sizes.
Conversely, pursuant to the invention an ideal pitch sequence for the reduction of noise in the longer belt may be compromised by the inclusion of pitch sequences within the long sequence for the purpose of manufacturing shorter belts from the same mold. The result may be a less than absolute noise reduction in the longer belt so as to optimize noise reduction in the shorter belt(s). However, again, an optimized trade off between the level of noise reduction in the longer belt and the smaller belt(s) may be achieved to accomplish a reduction in noise level in all belt sizes to an acceptably low level while preserving the flexibility of using a single mold in the manufacture of all belt sizes.
While the above describes a preferred embodiment for the practice of the invention, the invention is not intended to be so limited. Other embodiments that utilize the teachings herein set forth, are intended to be within the scope and spirit of the invention. | A multi-ribbed power transmission belt having longitudinal grooves and transverse grooves that form a plurality of cogs on the belt surface defined between adjacent transverse grooves is provided. The pitch lengths of the rows of cogs are randomized or sequenced over the entire length of the belt to reduce the noise of the belt as it travels about its associated pulleys. The ideal pitch pattern on a belt is variable, dependent upon the circumferential length of the belt. To create an optimized pitch sequence for belts of various circumferential lengths, a method of manufacture is employed wherein a portion of the pitch sequence of a shorter belt is incorporated within an optimized pitch sequence of a longer belt and both belts are manufactured from a single mold. The longer belt may contain cogs of various shapes intended to offset a range of frequencies and minimize noise generation. By selecting a certain span of the longer belt for the creation of smaller belt(s), a single mold may be utilized for producing belts of varying length and the noise characteristics of the belt may be controlled and optimized. | 1 |
BACKGROUND OF THE INVENTION
The invention relates to fluid reaction surfaces such as impellers and the like. More in particular, the invention relates to rotors having flow confining or deflecting webs, shrouds or continuous passages. Material blenders are exemplified by such devices as U.S. Pat. No. 2,692,127 to Conn. Conn discloses an improved blender comprising a spindle carrying adjacent one end an outwardly extending annular disc. The disc has circumferentially spaced openings extending therethrough wherein material deflecting hoods carried by the disc extend across the openings for directing material through the openings from one side of the disc to the other. Deflectors are carried by the disc and extend outwardly from the side thereof remote from the hoods in advance of the openings.
Another example of a blending apparatus is U.S. Pat. No. 3,606,577 to Conn. In this patent, Conn discloses peripheral teeth which alternate in an up-and-down pattern. As a group, the teeth may be inclined relative to the plane of the disc at angles varying over a wide range. Thus, in FIG. 4 of U.S. Pat. No. 3,606,577, mixing teeth are disclosed which angle at an inclination to the plane of the disc approximately 45 degrees.
While the apparatus of Conn provides certain degrees of mixing, cutting and masticating, there is room for improvement such that mixing and blending can be effected more efficiently with less energy expense. Therefore it is an object of this invention to provide an apparatus which blends, mixes and masticates material more efficiently than the prior art devices. It is another object of the invention to provide a rotor disc having mixing teeth located on peripheral edges which not only alternate in up-and-down patterns and vary in angular inclination to the plane of the disc over a range of degrees, but which provides mixing teeth which vary one from another in angular inclinations to the plane of the disc such that mixing, masticating and blending occur more rapidly and in a less regular fashion.
It is still another object of the invention to provide a disc which presents an irregular cutting pattern and irregular transmitting of materials through the openings such that more efficient mixing, blending and cutting occur.
It is yet another object of the invention to provide an apparatus having one or more stirrers mounted on one or more shafts to provide different mixing patterns and degrees of mixing.
It is still yet another object of the invention to provide stirrers that may be left- and right-handed to increase mixing and mastication.
These and other further objects and features of the invention are apparent in the disclosure, which includes the foregoing and following specification, claims and drawings.
SUMMARY OF THE INVENTION
The invention is a material mixing apparatus comprising a stirrer fixedly mounted on a shaft for mixing and masticating material. More than one stirrer may be assembled on more than one shaft to provide different mixing patterns and degrees of mixing. The stirrer is preferred to be a round, flat disc provided with attachment means for mounting on a shaft. The disc has openings which are slot-like and which are circumferentially spaced about the disc. The openings are radially aligned and preferably varied in size and shapes depending upon the mixing and masticating needs of a particular situation. Each opening has first and second edges which oppositely extend from the surface of the disc for conveying materials through said openings. That is to say, one side of the opening will extend outwardly from the disc and the other side of the opening will extend outwardly, yet in an opposite direction. The edges of the openings extend in a direction which is perpendicular to the plane of the disc.
Preferably, the length of extensions of the edges outwardly from the disc may vary. Also, the length of the openings may vary. For example, the slot-like openings may extend one-quarter of a radius of the disc to about 100 percent of said radius.
Mixing teeth are located along and extend from the peripheral edge of the disc. The teeth may alternate in direction of extension from the plane of the disc. That is to say, adjacent teeth will extend generally in opposite directions from each other. It is preferred that the teeth be varied in angular inclinations to the plane of the disc. The range of inclinations preferably being 0 degrees to about 90 degrees. Thus, one particular tooth will extend at a 90-degree angle to the plane of the disc and an adjacent tooth will extend in an opposite direction at a 45-degree angle to the disc, and a third tooth may extend in an opposite direction relative to the second tooth (i.e., in the same general direction relative to the plane of the disc as the first tooth) at a 60-degree angle to the plane of the disc, and so forth.
The discs are mounted on rotatable shafts in a fixed fashion. Preferably a set screw threadably received in a channel in the hub allows the set screw to press against a surface of the rotatable shaft for rigidly maintaining the hub in fixed relation thereto. Alternatively, the disc can be secured to an end of a shaft by means of driving pins extending between the end of the shaft and through the disc for retaining the disc as rotatable in relation to the shaft. A bolt and an optional bushing plate is used for removable fixed attachment of the disc to the shaft. Thus, when the shaft is rotated the disc or stirrer is rotated therewith. The shaft may be rotated and controlled in the rotation by any suitable means such as an electric motor equipped with a rheostat.
When one stirrer is mounted on a shaft and used for mixing or blending materials, the stirrer will cause the material being cut and blended to travel through the openings. A horizontally oriented stirrer or disc will have openings wherein one side of the opening is depressed downwardly and the other side of the opening is projected upwardly such that material being mixed moves along the depressed surface towards the upwardly projecting surface. As material moves into the opening it further follows the underside of the upwardly projecting surface downwardly and outwardly towards the mixing teeth. The mixing teeth then catch the downwardly and outwardly moving material to further cut, masticate and mix the material.
The invention provides for increased mixing of material by placing two stirrers on one shaft in an opposed mutually spaced relationship wherein a mixing space between the stirrers is provided. It is preferred that the two discs be left-handed and right-handed or one reversed from the other. The opposed relation of the multiple discs is to provide for the transmission of materials through the openings into the space located between the stirrers wherein material being blended is forced into the space and out towards the mixing and cutting teeth.
The invention provides for mounting of opposed stirrers on contrarotating shafts which are juxtaposed end to end, wherein one stirrer is right-handed and the other stirrer is left-handed such that the direction of transmitting material through the openings is different from one disc to the other.
BRIEF DESCRIPTION OF THE DRAWINGS
While the specification concludes with claims particularly pointing out and distinctly claiming the subject matter that is regarded as forming the present invention, it is believed that the invention will be better understood from the following description accompanied by the following drawings in which:
FIG. 1 is a top plan view of one embodiment of the stirrer according to the invention;
FIG. 2 is a side plan view of two stirrers as shown in FIG. 1 mounted on a shaft;
FIG. 3 is a cross section taken along line 3--3 of FIG. 1;
FIG. 4 is a partial elevated perspective showing one embodiment of the louvers according to the invention;
FIGS. 4a-4c are partial elevated perspectives showing alternate embodiments of the louvers of figure 4; and
FIG. 5 is side plan view in partial cutaway of one of the attachment means according to the invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring to FIG. 1, a cutting blade generally designated 1 is shown. The blade 1 is flat and round and has a hub 16 for mounting on a shaft 13. The hub 16 has outer wall 11 and inner wall 12. Inner wall 12 defines a channel through the disc 1 wherein shaft 13 is received.
The surface 10 has located thereon circumferentially spaced and radially aligned openings 9. Each opening 9 is provided with a first edge 8 and a second edge 6. Edges 6 and 8 extend in opposite directions from the surface 10 such that there is a raised portion 5 and depressed portion 7. The structure 5, 6, 7, 8 and 9 is generally referred to as a louver. Thus, the disc 1 is provided with louvers 17, 18, 19, 20, 21 and 22 on the surface 10. It should be noted that other numbers of louvers can be used.
On the peripheral edges of disc 1 there is located mixing teeth 23 and 24. The mixing teeth are located along the circumferential periphery of disc 1. For purposes of discussion, only two teeth in FIG. 1 will be described. Mixing tooth 23 extends in a direction similar to the raised surface 5 and tooth 24 extends in a direction similar to that of depressed surface 7. Referring to FIG. 2, there is shown two discs which are both generally designated as 1 mounted on shaft 13 in an opposed and mutually spaced relationship such that space 29 is defined therebetween. Arrow 15 in FIG. 1 defines the rotation of shaft 13. As shaft 13 rotates, material which is being blended is drawn through the openings in the direction of arrows 25 and 26. Material that has been drawn into space 29 is urged outwardly towards the periphery of the discs 1 and is further blended and cut by the teeth 23 and 24. Material being cut by the teeth is urged in the direction of arrows 27 and 28.
Referring to FIG. 3, the disc 1 is shown in cross section. Hub 16 is centrally located on the disc 1. Inner wall 12 of hub 16 defines a cylindrical channel 31 which is adapted to slidably receive rotatable shaft 13 as depicted in FIGS. 1 and 2. The disc 1 is fixedly mounted on shaft 13 by way of a set screw (not shown) being inserted in channel 14. Channel 14 is preferably lined with threads and is adapted to threadably engage a set screw which presses against surfaces of the shaft 13.
The oppositely extending edges 6 and 8 are shown more clearly in FIG. 3. Opening edge 6 extends upwardly and opening edge 8 extends downwardly as shown in the embodiment of FIG. 3. Thus, upwardly extending edge 6 has an associated concave surface 30 located on a lower surface of the disc 1 and convex surface 5 located on an upper surface of disc 1. Similarly, downwardly extending opening edge 8 has associated concave surface 7 located on an upper face of disc 1 and a convex surface 31 located on a lower surface of disc 1. As should be readily apparent, the louver on disc 1 comprises opening edges 6 and 8, concave surfaces 7 and 30, convex surfaces 5 and 31, and opening 9.
FIG. 4 shows the louvers of the invention in perspective. As shown, the louvers are ovoid holes in radial extension between the central disc area and the periphery. The holes have raised portion 44 and depressed portion 46. It should be noted that portions 44 and 46 can vary in degree of extension. For example, figure 4a shows raised portion 48 and depressed portion 50 forming a more open and less ovoid opening. FIG. 4b shows a still wider opening with raised portion 52 and depressed portion 54 forming an almost diamond shaped opening. FIG. 4c shows a slight variation wherein raised portion 56 and depressed portion 58 are flat sided at the most extended areas. As was noted above, any number of louvers may be positioned about the circumference of the disc depending upon the job at hand. Additionally, the louvers may vary in opening sizes either from disc to disc or from louver to louver upon a disc.
Referring to FIG. 5, an alternate method of attachment is shown. The shaft 13' is shown with driving pins 34 and 36 extending between the end of the shaft 13' and the disc 1'. Holes are located on the disc 1' for receiving the driving pins 34 and 36. As shown, a bushing 32 can be used in conjunction with a threaded lug 42 and nut 40 to removably attach disc 1' to the central shaft 13'.
In operation, the apparatus of FIG. 2 is rotated clockwise in an area containing unblended materials. Stirrers may be made opposite hand so that the shaft may be rotated counter-clockwise if necessary. Opening edge 6 captures material and conveys the material inwardly towards the space between the discs along concave surface 30. The associated depressed surface 7 serves to help direct material towards surface 30. Material moves inwardly in the direction of arrows 25 and 26 and outwardly towards mixing teeth 23 and 24. Arrows 27 and 28 depict the movement of materials around the teeth. The irregularity of the angular inclination of teeth ensures a variety of cutting edges in contact with the material such that effective cutting and mixing occur. The irregular cutting pattern which results from the variety of angular orientations at which the two groups of teeth (i.e., those which point either upwardly or downwardly from the plane of the disc 1) are inclined relative to the plane of the disc 1 provides superior mixing by mixing an entire three-dimensional "zone" of material rather than merely a two-dimensional "plane" of material as is the case with other devices.
As this invention may be embodied in several forms without departing from the spirit or essential characteristics thereof, the present embodiment is therefore illustrative and not restrictive, and since the scope of the invention is defined by the appended claims, all changes that fall within the metes and bounds of the claims or that form their functional as well as their conjointly cooperative equivalents are therefore intended to be embraced by those claims. | A blending apparatus has a rotor provided with louvers and mixing teeth. The louvers have openings which vary in size and act to convey materials being cut and blended through the disc. The mixing teeth extend from peripheral edges of the rotor. Adjacent teeth vary in angular extension from the edges and in direction of extension from the edges. One or more rotors may be mounted on one or more shafts to meet diverse mixing needs. | 1 |
FIELD OF THE INVENTION
[0001] The present invention relates to sugar cane harvesters, and more specifically, relates to topper/shredders for such harvesters.
BACKGROUND OF THE INVENTION
[0002] Sugar cane harvesters are equipped with sugar cane topping devices which take off the upper part of a sugar cane stalk since it does not contain a worthwhile amount of sugar. Conventional topping devices operate such that the top of the sugar cane stalk is severed and thrown into the furrow adjacent to the row being harvested. The transport vehicle runs upon the discarded tops on the next pass through the field. In wet weather this becomes a problem. The tops tend to collect and are pushed in front of the non-powered front tires of the transport tractor or the non-powered tires of the transport wagon. This continues until the transport can no longer push the pile. If at this point, the pile is too high to climb, the transport must back up and try to jump the pile. This problem can get so bad that harvesting operations must be suspended.
[0003] In order to alleviate this “bull dozing” operation, topper/shredders have been used that shred the tops into smaller pieces. An example of a topper/shredder is disclosed in U.S. Pat. No. 6,363,700, granted to Fowler on Apr. 2, 2002. These devices have been used on both wholestick and chopper harvesters for many years, and are not as efficient in throwing the small shredded pieces as far as the conventional whole piece toppers. This results in some portion of the tops dropping into the throat of the harvester. To deliver cane having no more extraneous matter than that delivered by a harvester equipped with a conventional whole piece topper, the forward speed of the machine must be reduced.
SUMMARY OF THE INVENTION
[0004] According to the present invention there is provided an improved topper-shredder for use with a sugar cane harvester.
[0005] It is an object of the invention to provide a topper/shredder capable of depositing shredded cane stalk tops outwardly of the path followed by the throat of the harvester.
[0006] The above object is accomplished by a topper/shredder which incorporates blades for creating an air flow which aids in propelling the shredded cane top pieces outside the row being harvested.
[0007] This and other objects of the invention will become apparent from a reading of the ensuing description together with the appended drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] FIG. 1 is a left front perspective view of a sugar cane harvester embodying a topper/shredder constructed in accordance with the principles of the present invention.
[0009] FIG. 2 is an exploded view of the topper/shredder shown in FIG. 1 .
[0010] FIG. 3 is a top view of the right-hand cane top gathering device shown in FIG. 2 .
[0011] FIG. 4 is a vertical sectional view taken along line 4 - 4 of FIG. 3 .
DESCRIPTION OF THE PREFERRED EMBODIMENT
[0012] Referring now to FIG. 1 , there is shown a sugar cane combine or chopper harvester 10 including a main frame 12 supported on front and rear pairs of wheels 14 and 16 , respectively. Mounted on a forward location of the frame 12 is an operator's cab 18 containing the various controls for operating the harvester 10 .
[0013] Mounted to the forward end of the frame 12 are various components for harvesting a single row of sugar cane. Specifically, right-and left-hand row dividers 20 and 22 are provided for operation at opposite sides of a throat area 24 where a row of cane passes for being cut off by a pair of base cutters (not visible). The row dividers 20 and 22 respectively include spiral lifting devices 26 and 28 for elevating down or recumbent cane.
[0014] Located centrally between the row dividers 20 and 22 and coupled to the main frame 12 is a cane topper/shredder assembly 30 including a parallel linkage defined by parallel, upper and lower support arms 32 and 34 , respectively. The upper and lower support arms 34 and 36 have respective rear ends pivotally coupled, as at upper and lower horizontal transverse pins 36 and 38 , to upper and lower locations of an U-shaped bracket 40 fixed to an upper front location of the frame 12 . Referring now also to FIG. 2 , while hidden, it will be understood that respective forward ends of the parallel arms 32 and 34 are pivotally coupled to upper and lower locations of a U-shaped bracket 42 located at a center, rear location of a topper/shredder frame 44 . Provided for adjusting the height of the topper/shredder is an extensible and retractable hydraulic cylinder 46 having its head end pivotally coupled to the harvester frame 12 and having its rod end pivotally attached to the lower arm 34 .
[0015] The topper/shredder frame 44 includes right- and left-hand, L-shaped tubular support members 48 and 50 , respectively. The right-hand support member 48 includes a horizontal section 51 R and a vertical section 52 R, with the latter extending along a vertical axis Y. A hydraulic motor mounting ring 53 R is welded, or otherwise fixed, within a lower part of the vertical section 52 R and a stop ring 54 R is received on and fixed to an upper location of the vertical section 52 R. Similarly, the left-hand support member 50 includes a horizontal section 51 L and a vertical section 52 L, with the latter extending along a vertical axis Y′. A hydraulic motor mounting ring 53 L is fixed within a lower part of the vertical section 52 L, and a stop ring 54 L is received on and fixed to an upper part of the vertical section 52 L. The horizontal sections 51 R and 51 L diverge forwardly from each other.
[0016] The frame 44 has right- and left-hand wing sections 56 and 58 which include forwardly facing surfaces 60 and 62 that are respectively curved about the vertical axes Y and Y′. The wing sections 56 and 58 have respective parallel, vertical, fore-and-aft extending inner walls 64 and 66 . The inner wall 64 includes four vertically spaced, horizontal, knife-mounting slots 68 in which are mounted stationary cutting knives 70 . Similarly, four vertically spaced knife-mounting slots 72 are provided in the inner wall 66 and are provided with stationary cutting knives (not visible).
[0017] Located centrally between the tubular support members 48 and 50 is a central or middle tubular support member 74 comprising a horizontal section 76 and a vertical section 78 disposed along a vertical axis Y″. The horizontal section 76 of the third support member 74 is considerably shorter than the horizontal sections 52 R and 52 L, with the vertical section 78 being approximately centered in a vertical, transverse plane joining respective forward edges of the inner walls 64 and 66 . A hydraulic motor mounting ring 80 is received within and fixed to a lower location of the vertical section 78 , and a stop ring 82 is received on and fixed to an upper location of the vertical section 78 .
[0018] A topper/shredder rotor 84 includes a central cylindrical tube 86 received on, and mounted for rotation about, the vertical section 78 of the central support member 74 . A reversible, hydraulic motor 88 includes an upper body projecting upwardly within the motor mounting ring 80 . A mounting flange 90 at the bottom of the body is positioned against, and bolted to, the mounting ring 80 . Hydraulic fluid supply/return hoses 92 and 94 are coupled to respective upper locations of the motor body and extend through the tubular support member 48 . The rotor tube 86 is received on the vertical section 78 of the central tubular support member 74 , with the upper end of the tube 86 abutting the stop ring 82 . Suitable bearings (not shown) support the rotor tube 86 for rotation about the axis Y″. A splined motor drive hub 96 is received on a splined output shaft (not shown) projecting from the bottom of the motor 88 . A circular drive plate 98 is welded within a lower end of the rotor tube 86 , and the drive hub 96 is secured to the drive plate 98 by a plurality of screws (not shown).
[0019] The chopper/shredder rotor 84 further includes four vertically spaced, knife mount disks 100 , and each disk has eight cutting knives 102 fixed about its periphery at equally spaced locations. The spacing of the disks 100 is such as to have the knives 102 pass closely adjacent fixed knives mounted within the knife mounting grooves 68 and 72 , respectively, located in the right- and left-hand wings 56 and 58 . Fixed to, and extending radially from the, rotor tube 86 and located between and fixed to adjacent disks 100 are a plurality of fins 104 , which not only rigidify the disks 100 but act to generate air flow. This air flow is aided by a plurality of circular holes 106 located in a circular pattern in each of the disks 100 at respective radial locations approximately halfway between the axis Y″ and the path traced by the outer tips of the knives 102 .
[0020] Cane tops are gathered for being processed by the topper/shredder rotor 84 by right- and left-hand gathering rotors 110 and 112 , respectively, that include central cylindrical tubes or cores 112 R and 112 L, respectively mounted for rotation about the vertical sections 52 R and 52 L of the support tube members 48 and 50 . Provided for driving the gathering rotors 110 R and 110 L are right-and left-hand hydraulic motors 114 R and 114 L, respectively, the motors having respective bodies inserted through the motor mounting rings 53 R and 53 L, with the bodies having respective mounting flanges 116 R and 116 L engaged with, and bolted to the mounting rings 53 R and 53 L. The hydraulic motor 114 R includes a pair of hydraulic fluid supply/return hoses 118 and 120 which extend through the tubular support member 48 from respective fittings adjacent an upper location of the body of the motor 114 R. Similarly, the hydraulic motor 114 L includes a pair of hydraulic fluid supply/return hoses 122 and 124 which extend through the tubular support member 50 from respective fittings adjacent an upper location of the body of the motor 114 L. Fixed to respective splined output shafts (not shown) projecting down from the lower end of the hydraulic motors 114 R and 114 L are respective drive hubs 126 and 128 . As can best be seen in FIGS. 3 and 4 , circular drive plates 130 and 132 are respectively fixed within the lower ends of the rotor tubes 112 R and 112 L. The tubes 112 R and 112 L respectively have upper ends engaged with the stop rings 54 R and 54 L. The drive plates 130 and 132 are then respectively positioned against, and secured to the drive hubs 126 and 128 by a plurality of screws (not shown). The motors 114 R and 114 L are each reversible, and with respect to being viewed from the top, the motor 114 R is controlled for driving the gathering rotor 110 R counterclockwise, and the motor 114 L is controlled for driving the gathering rotor 110 L clockwise.
[0021] The gathering rotors 110 R and 110 L further include respective sets of three vertically spaced gathering disks 130 R and 130 L which are respectively welded to the rotor tubes 112 R and 112 L. Arranged at equally spaced locations about the periphery of each of the gathering disks 130 R and 130 L are respective sets of eight gathering projections 132 R and 132 L. Projecting radially from and fixed to the rotor tubes 112 R and 112 L, and extending between and fixed to adjacent ones of the gathering disks 130 R and 130 L are fan blades 134 R and 134 L. While the blades 134 R and 134 L may be of any desired shape capable of generating an air stream for aiding in conveying cane top pieces outwardly beyond the throat 24 of the harvester 10 , they are here shown as having a simple shape comprising a major straight base section that is joined to a tip section curved or angled from the base section such that it leads in the direction of rotation of the respective gathering rotor 110 R and 110 L. The flow of air generated by the fan blades 134 R and 134 L is aided by a plurality of circular air passages 136 and 138 , respectively provided in each of the gathering disks 130 R and 130 L.
[0022] The operation of the topper/shredder 30 is as follows. Assuming that the harvester 10 is harvesting a row of cane of a plot of standing cane located to the right-hand side of the harvester 10 , the hydraulic motor 88 will be controlled to cause the topper/shredder rotor 84 to be rotated counterclockwise, as viewed in FIG. 2 . At the same time, the hydraulic motors 114 R and 114 L will be respectively controlled for driving the gathering rotors 110 R and 110 L counterclockwise and clockwise, as viewed in FIG. 2 .
[0023] With the topper/shredder rotor 84 rotating counterclockwise, the cutting knives 102 will engage and carry cane tops being delivered to it by the projections 132 R of the gathering rotor 110 R into engagement with the gathering rotor 110 L, which in turn carries the cane tops to the point where they are cut into pieces by the cooperative cutting action of the knives 102 and the stationary blades mounted in the blade mount grooves 72 and 78 . Furthermore, the fins 104 of the rotor 84 will tend to deflect the air stream delivered by the fan blades 134 R to the left where it is again deflected by the fan blades 134 L and caused to flow to the left in front of the curved surface 62 of the left wing 58 of the frame 44 . This stream of air will entrain the cut pieces of cane top and deliver it sideways with sufficient force to cause most of the top material to be deposited to the left of the throat 24 of the harvester 10 .
[0024] It will be understood that when harvesting a row of cane from a plot of cane located to the left of the harvester 10 , the chopper/shredder rotor 84 will be rotated in the clockwise direction resulting in the generated air stream passing outwardly in front of the curved surface 60 so as to carry top pieces to the right of the throat 24 of the harvester.
[0025] Having described the preferred embodiment, it will become apparent that various modifications can be made without departing from the scope of the invention as defined in the accompanying claims. | A topper/shredder arrangement of a cane harvester is designed so that a stream of air is created that aids in carrying pieces of cane tops to a location outside the harvesting throat of the cane harvester. | 0 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a disc molding die.
2. Description of the Related Art
Conventionally, when a product is molded in an injection molding machine, resin supplied to a heating cylinder is heated and melted therein and then charged into a cavity formed in a die. The molten resin is then cooled and hardened to obtain the molded product.
In the case where products to be molded are discs such as optical disc substrates, resin supplied to the heating cylinder is heated and melted therein and then charged into a cavity formed in a disc molding die. The molten resin is then cooled and hardened to obtain the molded products.
The disc molding die is composed of a stationary die assembly and a movable die assembly. A die clamping apparatus causes a movable mirror-surface plate of the movable die assembly to contact with and separate from a stationary mirror-surface plate of the stationary die assembly, thereby performing die closing, die clamping, and die opening.
However, in the conventional disc molding die, the mirror-surface plates must be replaced whenever discs having a different thickness are to be molded.
Therefore, the mirror-surface plates must be made for each kind of disc. In addition, since discs are required to have excellent optical characteristics, accuracy of the mirror-surface plates, as measured by, for example, surface roughness and dimensional accuracy, must be increased. As a result, the cost of the disc molding die increases and a prolonged period of time is required to manufacture the disc molding die.
Moreover, for replacement of the mirror-surface plates, the following operations must be carried out: First, the stationary die assembly and the movable die assembly are removed from the die clamping apparatus, and the respective mirror-surface plates are then replaced with other mirror-surface plates. Subsequently, the stationary die assembly and the movable die assembly are attached to the die clamping apparatus. In addition, the replacement of the mirror-surface plates requires disconnection and reconnection of pipes for water, air, etc. Accordingly, the operations involved in the replacement of the mirror-surface plates are troublesome and greatly decrease the productivity of the injection molding machine.
SUMMARY OF THE INVENTION
An object of the present invention is to solve the above-mentioned problems in the conventional disc molding die and to provide a disc molding die which can eliminate the necessity of making different mirror-surface plates for each kind of disc in order to lower the cost and to shorten the manufacturing period and can simplify the operations in order to improve the productivity of the injection molding machine.
To achieve the above object, a disc molding die according to the present invention comprises a stationary platen; a movable platen disposed so as to face the stationary platen and adapted to be advanced and retracted by a die clamping apparatus; a stationary base plate attached to the stationary platen; a movable base plate attached to the movable platen; a stationary mirror-surface plate attached to the stationary base plate; a movable mirror-surface plate attached to the movable base plate; a stationary guide ring attached to the stationary base plate so as to surround the stationary mirror-surface plate; a movable guide ring attached to the movable base plate so as to surround the movable mirror-surface plate and adapted to contact with the stationary guide ring in a die clamp state; a cavity ring detachably attached to one of the stationary and movable mirror-surface plates such that the cavity ring projects toward the other of the stationary and movable mirror-surface plates; and abutment position adjusting means for adjusting a position where the movable guide ring abuts on the stationary guide ring, in accordance with the thickness of the cavity ring.
When the movable platen is advanced by the die clamping apparatus, the cavity ring attached to one of the stationary and movable mirror-surface plates abuts on the other of the stationary and movable mirror-surface plates, so that a cavity is formed.
When the cavity ring is replaced with a different one having a different thickness, the abutment position of the guide rings is adjusted by the abutment position adjusting means in accordance with the thickness of the newly attached cavity ring. This allows the thickness of the cavity to be changed without replacement of the mirror-surface plates.
Since it is unnecessary to make mirror-surface plates for each kind of disc, the cost of the disc molding die can be lowered, and the period of time required to manufacture the disc molding die can be shortened.
In addition, it is unnecessary to remove the stationary and movable die assemblies from the die clamping apparatus and attach different stationary and movable die assemblies to the die clamping apparatus, and to disconnect and reconnect pipes for water, air, etc., in order to adjust the abutment position of the guide rings by the abutment position adjusting means. Accordingly, the operations can be simplified and the productivity of the injection molding machine can be improved.
In another disc molding die according to the present invention, the abutment position adjusting means is a guide ring spacer that is removably disposed between the guide ring and the base plate.
In this case, when the cavity ring is replaced with a different one having a different thickness, the guide ring spacer is attached or removed in accordance with the thickness of the newly attached cavity ring. This allows the thickness of the cavity to be changed without replacement of the mirror-surface plates.
In still another disc molding die according to the present invention, the abutment position adjusting means is a guide ring spacer that is removably disposed between the guide rings.
In this case, when the cavity ring is replaced with a different one having a different thickness, the guide ring spacer is attached or removed in accordance with the thickness of the newly attached cavity ring. This allows the thickness of the cavity to be changed without replacement of the mirror-surface plates.
Still another disc molding die according to the present invention comprises a stationary platen; a movable platen disposed so as to face the stationary platen and adapted to be advanced and retracted by a die clamping apparatus; a stationary base plate attached to the stationary platen; a movable base plate attached to the movable platen; a stationary mirror-surface plate attached to the stationary base plate; a movable mirror-surface plate attached to the movable base plate; a stationary guide ring attached to the stationary base plate so as to surround the stationary mirror-surface plate; a movable guide ring attached to the movable base plate so as to surround the movable mirror-surface plate and adapted to contact with the stationary guide ring in a die clamp state; and a cavity ring detachably attached to one of the stationary and movable mirror-surface plates such that the cavity ring projects toward the other of the stationary and movable mirror-surface plates.
The guide ring is replaced with a different one in accordance with the thickness of the cavity ring so as to adjust the abutment position of the guide ring.
In this case, when the cavity ring is replaced with a different one having a different thickness, one of the guide rings is replaced with a different one in accordance with the thickness of the newly attached cavity ring. This allows the thickness of the cavity to be changed without replacement of the mirror-surface plates.
BRIEF DESCRIPTION OF THE DRAWINGS
The structure and features of the disc molding die according to the present invention will be readily appreciated as the same becomes better understood by referring to the accompanying drawings, in which:
FIG. 1 is a sectional view of a disc molding die according to a first embodiment of the present invention;
FIG. 2 is a view showing a first state of the abutment position adjusting means in the first embodiment of the present invention;
FIG. 3 is a view showing a second state of the abutment position adjusting means in the first embodiment of the present invention;
FIG. 4 is a view showing a first state of the disc moldig die in a second embodiment of the present invention;
FIG. 5 is a view showing a second state of the disc molding die in the second embodiment of the present invention;
FIG. 6 is a view showing a first state of the abutment position adjusting means in a third embodiment of the present invention;
FIG. 7 is a view showing a second state of the abutment position adjusting means in the third embodiment of the present invention;
FIG. 8 is a view showing a first state of the abutment position adjusting means in a fourth embodiment of the present invention;
FIG. 9 is a view showing a second state of the abutment position adjusting means in the fourth embodiment of the present invention;
FIG. 10 is a view showing a first state of the abutment position adjusting means in a fifth embodiment of the present invention; and
FIG. 11 is a view showing a second state of the abutment position adjusting means in the fifth embodiment of the present invention.
DESCRIPTION OF PREFERRED EMBODIMENT
Embodiments of the present invention will next be described in detail with reference to the drawings.
FIG. 1 is a sectional view of a disc molding die according to a first embodiment of the present invention.
In FIG. 1, numeral 12 denotes a stationary die assembly that is attached to an unillustrated stationary platen with bolts. The stationary die assembly 12 is composed of a base plate 15, a mirror-surface plate 16 fixed to the base plate 15 with bolts 17, an annular guide ring 18 disposed to surround the mirror-surface plate 16 and fixed to the base plate 15 with bolts 19, a locating ring 23 that is disposed on the stationary-platen side of the base plate 15 so as to locate the base plate 15 with respect to the stationary platen, and a sprue bush 24 disposed adjacent to the locating ring 23.
At the center of the sprue bush 24 is formed a sprue 26 through which resin injected from an unillustrated injection nozzle passes. The sprue bush 24 is disposed such that its tip end faces a cavity C, and a cut die 28 is formed in the end surface of the sprue bush 24.
Moreover, unillustrated stamper plate attachment/removal bushes, a stationary-side air-blow bush, and the like are disposed on the stationary die assembly 12.
Numeral 32 denotes a movable die assembly that is attached to an unillustrated movable platen with bolts. The movable die assembly 32 is composed of a base plate 35, an intermediate plate 40 fixed to the base plate 35 with bolts 37, a mirror-surface plate 36 fixed to the intermediate plate 40 with bolts 42, an annular guide ring 38 disposed to surround the mirror-surface plate 36 and fixed to the intermediate plate 40 with bolts 39, a cylinder 44 that is disposed within the base plate 35 so as to face the movable platen and fixed to the base plate 35 with bolts 45, and a cut punch 48 that is advanced and retracted by the cylinder 44 and that has a shape corresponding to the cut die 28.
Moreover, on the surface of the mirror-surface plate 36 facing the mirror-surface plate 16 is disposed an annular cavity ring 71 that extends along the outer circumferential edge of the surface. The annular cavity ring 71 is fixed to the mirror-surface plate 36 with unillustrated bolts and projects toward the mirror-surface plate 16 by an amount corresponding to the thickness of a disc to be molded. As a result, a concave portion is formed on the radially inner-side of the cavity ring 71. When the movable platen is moved toward the stationary platen through an operation of an unillustrated die clamping apparatus and the cavity ring 71 is brought into contact with the mirror-surface plate 16, the concave portion forms the cavity C.
A piston 51 integrally formed with the cut punch 48 is reciprocatively disposed within the cylinder 44. An oil chamber is formed on the rear side (movable-platen side) of the piston 51. On the front side (upper side in FIG. 1) of the piston 51, a cut-punch returning spring 52 is disposed in order to urge the piston 51 rearward.
In the disc molding die having the above-described structure, when the movable platen is moved toward the stationary platen through operation of the die clamping apparatus, the guide ring 38 coincides with the guide ring 18, so that the cavity ring 71 is centered with respect to the mirror-surface plate 16, therby performing the die clamping. In the die clamp state, molten resin is charged into the cavity C via the sprue 26, and is then cooled and hardened to obtain a molded product.
In order to coincide the guide ring 38 with the guide ring 18 as described above, an annular projection 18a is formed on the guide ring 18 at its outer circumferential side, while an annular projection 38a is formed on the guide ring 38 at its inner circumferential side.
Subsequently, when the piston 51 is advanced (moved upward in FIG. 1) by supplying an oil to the above-mentioned oil chamber, the cut punch 48 is advanced, so that the tip end of the cut punch 48 enters the cut die 28. As a result, a hole is formed in the product in the cavity C, whereby the center portion of the disc is removed.
Unillustrated ejector bushes, ejector pins, a movable-side air-blow bush, and the like are also disposed on the movable die assembly 32.
In the surface of the mirror-surface plate 16, which surface faces the base plate 15, grooves 61 is formed in an appropriate pattern. The grooves 61 are covered by the base plate 15 so as to form cooling water passages 62. The cooling water passages 62 are connected to an unillustrated cooling water system via an inlet manifold 63 and an outlet manifold 64.
Similarly, in the surface of the mirror-surface plate 36, which surface faces the intermediate plate 40, grooves 66 are formed in an appropriate pattern. The grooves 66 are covered by the intermediate plate 40 so as to form cooling water passages 67. The cooling water passages 67 are connected to the cooling water system via an inlet manifold 68 and an outlet manifold 69.
In order to prevent cooling water from leaking from the cooling water passages 62 and 67, the inlet manifolds 63 and 68, and the outlet manifolds 64 and 69, sealing is provided by unillustrated O-rings.
In the disc molding die having the above-described structure, different discs having different thicknesses can be molded without replacinng the mirror-surface plate 16, the cut die 28, etc. of the stationary die assembly 12 and the mirror-surface plate 36, the cut punch 48, etc. of the movable die assembly 32. To this end, the thickness of the cavity ring 71 can be changed, and abutment position adjusting means is provided so as to adjust the abutment position between the guide rings 18 and 38 in accordance with the thickness of the cavity ring 71.
FIG. 2 is a view showing a first state of the abutment position adjusting means in the first embodiment of the present invention, and FIG. 3 is a view showing a second state of the abutment position adjusting means in the first embodiment of the present invention.
In these drawings, numerals 15 and 35 denote the base plates, numerals 16 and 36 denote the mirror-surface plates, numerals 18 and 38 denote the guide rings, numeral 71a denotes a thick-type cavity ring, numeral 71b denotes a thin-type cavity ring, and numeral 72 denotes an annular guide ring spacer. The guide ring spacer 72 serves as the abutment position adjusting means.
When a disc to be molded is thick, the cavity ring 71a is attached to the mirror-surface plate 36, and the guide ring spacer 72 is disposed between the guide ring 38 and the base plate 35, as shown in FIG. 2. As a result, the amount of projection of the cavity ring 71a from the mirror-surface plate 36 increases, so that the thickness of the cavity C becomes t1.
When a disc to be molded is thin, the cavity ring 71b is attached to the mirror-surface plate 36, and the guide ring 38 is brought into close contact with the base plate 35, as shown in FIG. 3. As a result, the amount of projection of the cavity ring 71b from the mirror-surface plate 36 decreases, so that the thickness of the cavity C becomes t2.
As described above, when the cavity rings 71a and 72b having different thicknesses are used, the abutment position between the guide rings 18 and 38 is adjusted by the guide ring spacer 72 in accordance with the thickness of the cavity ring 71a or 72b. As a result, the thickness of the cavity C can be changed without replacing the mirror-surface plates 16 and 36.
Since it is unnecessary to make the mirror-surface plates 16 and 36 for each kind of disc, the cost of the disc molding die can be lowered, and the period of time required to manufacture the disc molding die can be shortened.
In addition, it is unnecessary to remove the stationary and movable die assemblies 12 and 32 from the die clamping apparatus and attach different stationary and movable die assemblies to the die clamping apparatus, and to disconnect and reconnect pipes for water, air, etc., in order to dispose the guide ring spacer 72. Accordingly, the operations can be simplified and the productivity of the injection molding machine can be improved.
Next, a second embodiment of the present invention will be described.
FIG. 4 is a view showing a first state of the disc molding die in the second embodiment of the present invention; and FIG. 5 is a view showing a second state of the disc molding die in the second embodiment of the present invention.
In these drawings, numerals 15 and 35 denote the base plates, numerals 16 and 36 denote the mirror-surface plates, numeral 18 denotes the guide ring, numeral 38a denotes a thick-type guide ring, numeral 38b denotes a thin-type guide ring, numeral 71a denotes the thick-type cavity ring, and numeral 71b denotes the thin-type cavity ring.
When a disc to be molded is thick, the cavity ring 71a is attached to the mirror-surface plate 36, and the guide ring 38a is attached to the base plate 35, as shown in FIG. 4. As a result, the amount of projection of the cavity ring 71a from the mirror-surface plate 36 increases, so that the thickness of the cavity C becomes t1.
When a disc to be molded is thin, the cavity ring 71b is attached to the mirror-surface plate 36, and the guide ring 38b is attached to the base plate 35, as shown in FIG. 5. As a result, the amount of projection of the cavity ring 71b from the mirror-surface plate 36 decreases, so that the thickness of the cavity C becomes t2.
Next, a third embodiment of the present invention will be described.
FIG. 6 is a view showing a first state of the abutment position adjusting means in the third embodiment of the present invention, and FIG. 7 is a view showing a second state of the abutment position adjusting means in the third embodiment of the present invention.
In these drawings, numerals 15 and 35 denote the base plates, numerals 16 and 36 denote the mirror-surface plates, numerals 18 and 38 denote the guide rings, numeral 71a denotes the thick-type cavity ring, numeral 71b denotes the thin-type cavity ring, and numeral 73 denotes an annular guide ring spacer. The guide ring spacer 73 serves as the abutment position adjusting means.
When a disc to be molded is thick, the cavity ring 71a is attached to the mirror-surface plate 36, and the guide ring spacer 73 is disposed between the guide ring 18 and the base plate 15, as shown in FIG. 6. As a result, the amount of projection of the cavity ring 71a from the mirror-surface plate 36 increases, so that the thickness of the cavity C becomes t1.
When a disc to be molded is thin, the cavity ring 71b is attached to the mirror-surface plate 36, and the guide ring 18 is brought into close contact with the base plate 15, as shown in FIG. 7. As a result, the amount of projection of the cavity ring 71b from the mirror-surface plate 36 decreases, so that the thickness of the cavity C becomes t2.
Next, a fourth embodiment of the present invention will be described.
FIG. 8 is a view showing a first state of the abutment position adjusting means in the fourth embodiment of the present invention, and FIG. 9 is a view showing a second state of the abutment position adjusting means in the fourth embodiment of the present invention.
In these drawings, numerals 15 and 35 denote the base plates, numerals 16 and 36 denote the mirror-surface plates, numeral 18a denotes a thick-type guide ring, numeral 18b denotes a thin-type guide ring, numeral 38 denotes the guide ring, numeral 71a denotes the thick-type cavity ring, and numeral 71b denotes the thin-type cavity ring. The guide rings 18a and 18b serve as the abutment position adjusting means.
When a disc to be molded is thick, the cavity ring 71a is attached to the mirror-surface plate 36, and the guide ring 18a is attached to the base plate 15, as shown in FIG. 8. As a result, the amount of projection of the cavity ring 71a from the mirror-surface plate 36 increases, so that the thickness of the cavity C becomes t1.
When a disc to be molded is thin, the cavity ring 71b is attached to the mirror-surface plate 36, and the guide ring 18b is attached to the base plate 15, as shown in FIG. 9. As a result, the amount of projection of the cavity ring 71b from the mirror-surface plate 36 decreases, so that the thickness of the cavity C becomes t2.
Next, a fifth embodiment of the present invention will be described.
FIG. 10 is a view showing a first state of the abutment position adjusting means in the fifth embodiment of the present invention, and FIG. 11 is a view showing a second state of the abutment position adjusting means in the fifth embodiment of the present invention.
In these drawings, numerals 15 and 35 denote the base plates, numerals 16 and 36 denote the mirror-surface plates, numerals 18 and 38 denote the guide rings, numeral 71a denotes the thick-type cavity ring, numeral 71b denotes the thin-type cavity ring, numeral 74a denotes an annular thick-type guide ring spacer, and numeral 74b denotes an annular thin-type guide ring spacer. The guide ring spacers 74a and 74b serve as the abutment position adjusting means.
When a disc to be molded is thick, the cavity ring 71a is attached to the mirror-surface plate 36, and the guide ring spacer 74a is attached to the guide ring 18, as shown in FIG. 10. As a result, the amount of projection of the cavity ring 71a from the mirror-surface plate 36 increases, so that the thickness of the cavity C becomes t1.
When a disc to be molded is thin, the cavity ring 71b is attached to the mirror-surface plate 36, and the guide ring spacer 74b is attached to the guide ring 18, as shown in FIG. 11. As a result, the amount of projection of the cavity ring 71b from the mirror-surface plate 36 decreases, so that the thickness of the cavity C becomes t2.
The present invention is not limited to the above-described embodiments. Numerous modifications and variations of the present invention are possible in light of the spirit of the present invention, and they are not excluded from the scope of the present invention. | In a disc molding die, a stationary base plate is attached to a stationary platen, and a stationary mirror-surface plate is attached to the stationary base plate. Further, a movable base plate is attached to a movable platen, and a movable mirror-surface plate is attached to the movable base plate. A stationary guide ring is attached to the stationary base plate so as to surround the stationary mirror-surface plate, while a movable guide ring is attached to the movable base plate so as to surround the movable mirror-surface plate. When the die is clamped, the movable guide ring is brought into contact with the stationary guide ring. A cavity ring is detachably attached to one of the stationary and movable mirror-surface plates such that the cavity ring projects toward the other of the stationary and movable mirror-surface plates. An abutment position adjusting mechanism adjusts the abutment position where the movable guide ring abuts on the stationary guide ring, in accordance with the thickness of the cavity ring. This makes it possible to change the thickness of the cavity without replacing the mirror-surface plates. | 1 |
This is a continuation of co-pending U.S. patent application Ser. No. 08/548,193 filed on Oct. 25, 1995 for "Telescoping Bathtub Assembly", now abandoned.
BACKGROUND OF THE INVENTION
The present invention relates generally to bath tubs and more particularly to a bathing tub for persons with some physical or mental impairment which generally results in the need for a bathing assistant. My invention is particularly useful for persons with impaired ambulatory ability, obesity, inadequate or unreliable judgment, persons who are susceptible to a loss of consciousness during the bathing process, and for those who have the desire for a safer, easier, more convenient method of bathing.
It will be appreciated by those skilled in the art that conventional bathtubs have a number of deficiencies in terms of their ability to serve the needs for physically or mentally impaired persons. First, it can be difficult for the physically or mentally impaired to get in or out of a conventional bathtub. Conventional bathtubs require a person to step over the side wall of the tub, an obstacle that may cause the physically impaired to trip and injure themselves in or about the tub. Also, the bathtub itself may have a slippery surface which is more difficult to navigate for the physically impaired, and non-slip surfaces and grab bars are often an inadequate solution for those who have minimal strength.
Showers do not necessarily solve the problem because of the danger of slip and fall accidents and the inability of sick and infirm persons to stand for an extended period of time during showers. Also, showers do not lend themselves to assisted bathing since the assistant would get sprayed during the showering process.
There have been several attempts to address the problems associated with assisted bathing. One of the primary efforts has been the hoist-type systems which involves placing the person in a hammock-like structure, hoisting him over a tub of water and lowering him into the tub for the bathing process. The primary problems with the hoist-type systems are the fact that such devices are awkward and dangerous to manipulate, as well as being dehumanizing and humiliating to the patient.
In addition to the hoist-type systems, there have been developed a number of side access bathing tubs in which the patient lowers or moves the side of the tub out of the way, sits into the tub, raises or moves the side of the tub back in place, has the tub filled with water and then engages in the bathing process. Problems with devices of this nature involve side door maintenance, and sealing to avoid leaks in the tub, delays in the tub filing process, having to empty the tub if the person has to get out of the tub before the bath is completed, etc.
Another approach has been to provide side access with a tub chamber that tilts for access. However, these devices as well as all other prior art side access bathing tubs cannot be pre-filled and the bather must suffer the discomfort while the tub is filling of sitting in a potentially cold tub during the extended time that it takes to fill the tub. Further, the tub surfaces cannot be pre-warmed by having the water in the tub immediately prior to the bather entering the tub and the bather can be scalded or chilled by the water as it is filling the tub or irritated or injured by undiluted additives added to the bath water while the bather is in the tub.
Practically all of these prior art efforts at solving problems associated with assisted bathing for the mentally or physically impaired involve structures that cannot be quickly drained and re-filled with the same bathing liquid resulting in a waste of water when the bather has to get out of the tub in the middle of the bathing process, for example to go to the toilet, involve dangers in egress and ingress in the tub, or are inconvenient to use. Further, these prior art devices do not deal with the problems associated with unattended immobility of the bather, loss of consciousness and the like that may result in drowning.
SUMMARY OF THE INVENTION
The assisted bathing device of the present invention overcomes the problems of the prior art by providing an adjustable height, side access bathing basket, and a remote reservoir that is moveable to fit about the basket after the bather is in the basket. In Applicant's invention, the bathing basket has an open front with a seating area, a back and opposing ends. The seating area can be adjusted in height and then fixed at a level approximately buttock high above a support surface so that a bather can easily slide into the seating area of the basket through the open front. Once the bather is in the basket, a front rail is moved into a closing position to provide the bather with some support across the front of the basket and to prevent the bather from falling out of the basket. Next, a remote reservoir which has been pre-filled with a bathing liquid, usually body temperature bathing water, is raised and surrounds the bathing basket or the bathing basket is lowered into the remote reservoir to accomplish the same effect. The water will flow at a rapid pace into the bathing basket and the bather will thus be quickly immersed to any level of immersion desired in water that has been pretempered to the desired temperature. At any time during the bathing process, the side access bathing basket may be adjusted to a perfect height for a bathing assistant to attend to the bather without having to bend over and place strain on the assistant's back.
If the bather has to go to the toilet during the course of the bathing process or even worse, if the bather becomes unconscious during the bathing process, the water can be drained quickly from the bathing basket by simply lowering the remote reservoir or raising the bathing basket out of the remote reservoir. The drain of the water from the basket is not limited by the plumbing structure associated with the system but rather the water simply drops as the remote reservoir drops. Also, the water can be retained in the remote reservoir if the patient has to leave the basket before the bath is completed; thereafter, he can return to the basket, and the same water can be used to complete the bathing process by simply raising the remote reservoir.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic, perspective view of the remote reservoir tub of the present invention.
FIG. 1a is a schematic, perspective view of an alternative structure of the remote reservoir tub of the present invention.
FIG. 2 is an exploded view in perspective of the tub of the present invention.
FIG. 3 is a view in perspective of the lifting mechanism of the present invention.
FIG. 4 is a more detailed perspective view of the tub of the present invention.
FIG. 5 is a front elevation of the present invention.
FIG. 6 is a longitudinal sectional view of the tub of the present invention.
FIG. 7 is a cross sectional view of the tub of the present invention with the remote reservoir down and the basket slipped forward.
FIG. 8 is a cross sectional view of the tub of the present invention with the remote reservoir down and the basket tilted for cleaning.
FIG. 9 is a schematic view showing the use of the tub of the present invention in eight distinct steps.
DESCRIPTION OF THE PREFERRED EMBODIMENT
The present invention will be best understood when considered in light of the following description of the preferred embodiment of the invention as is illustrated in FIGS. 1-9 of the accompanying drawings.
FIG. 1 illustrates schematically and in perspective, the tub 10 in its fully assembled configuration with the door to the tub opened. The tub 10 will generally be mounted on a floor-type surface 12 and may be positioned against a wall 14 or against two walls 14, 14' forming a comer location for the tub.
The tub 10 is fitted within a lower housing 16 and an upper housing 16' which would generally be molded or formed by the assembly of a number of panels. FIG. 1a shows tub 10A, a variation on the present invention where only the remote reservoir and the side door can be raised and lowered and only one housing is required. Both FIGS. 1 and 2 show both housings, but referring to FIG. 2, the panels that form the lower housing 16 have been identified by letters A, B, C, and D designating opposing ends A and B, a back C, and a front D, and the panels that form the upper housing 16' have been identified by letters A', B', C', D', and F' designating opposing ends A' and B', a back C', a front D', and a top F'. The front panel D' has a gap 18 which is generally open, having opposing parallel sides. Slots 20 are formed in the face of the opposing parallel sides of the gap 18 in panel D' of the upper housing 16'. Door 22 fits within the slots 20 and is movable between an open position with the door dropped into the lower part directly behind panel D of the lower housing 16 as is shown in FIGS. 1 and 2 and a closed position when the door 22 is raised to the top of panel D' of the upper housing 16'.
The door 22 that fits within the slots 20 in the opposing faces of gap 18 is an element of convenience and is not absolutely required for the operation of the tub. However, the door 22 can be raised into the closed position to enclose the housing 16' once a bather has been positioned within the basket of the tub in the manner as described hereinafter. The top edge of door 22 may be fitted with a cushioned pad 88 to cover the opening between the bathing basket 56 and lower housing 16. Said cushioned pad would provide a softer edge for bathers to cross over when entering or exiting the bathing basket and would provide a more comfortable edge for an assistant to rest their arms when the door 22 is in the raised position.
Door 22 can be conveniently raised because of the installation of counterbalance weights 24, which are connected to one end of cords 26. The cords 26 are connected at their opposite ends to the door 22 and the intermediate portion of the cords travel over pulleys 28 journaled within the housing 16'. This mechanism allows the door 22 to be lifted into position by releasing latch 81 and the door will be raised into its raised position by the counterbalance weights where it will securely latch at latches 82. The door 22 may be lowered by simultaneously releasing latches 82 and pressing the door down until latch 81 secures it in the lowered position.
The upper housing 16' has a ledge 30 around a U-shaped mouth 32 formed in the top panel F'. The mouth 32 provides an opening for the tub so that a person can sit in the tub and have a portion of his body extending above the top of the housing in the ordinary bathing arrangement.
Bathing basket 56 has an upper perimeter ledge which is shaped to conform to and mates with the ledge 30 in the upper housing 16' so that the bathing basket can rest within the housing and sit on the upper panel F' of the upper housing 16'. The bathing basket 56 is constructed of panels A", B", C", E" and F" and conforms substantially to the shape of the opening in the upper housing 16' created by the gap 18 and the mouth 32. Thus, panels A" and B" serve as the two ends of the bathing basket, panel C" serves as the back of the bathing basket, there is no front panel on the bathing basket other than panels D" which serve as a closure to the interior of the tub, and panel E" serves as the bottom of the bathing basket. A surface F" extends variously about the perimeter of the upper portion of the bathing basket and mates with the U-shaped panel F' of the upper housing 16' so that the bathing basket 56 can sit on the panel F' of the upper housing 16' and be supported by the housing within the opening created by the gap 18 and mouth 32.
The size of the panels A", B" and C" are such that when the bathing basket is resting on the panel F' of the upper housing 16', the bottom E" of the bathing basket 56 is located at a height coterminous with the lower extent of gap 18 at a distance h above the floor 12. The distance h is generally in the 2-21/2 foot range and is designed to create a convenient seat for the buttocks of a bather entering the tub. By this arrangement, the bather can sit on the bottom E" of the bathing basket 56 and easily "scoot" into the bathing basket to be in position for the bath. The open front of the bathing basket makes it particularly convenient for the physically or mentally impaired to get into the tub so that they may bathe themselves, or in the more likely situation, be bathed by a bathing assistant such as a hospital or nursing home staff member.
Once the bather, sometimes referred to in this description of the preferred embodiment of the invention as the "patient" because Applicant's invention is particularly adaptable to use in conjunction with the treatment of hospital and nursing home patients which are either mentally or physically impaired, is in the bathing basket, the remote reservoir tub 54 which has been filled with a bathing solution at the desired temperature, is raised into position about the bathing basket. The water will flow into the bathing basket very rapidly so that the patient does not have to sit in the bathing basket for any extended period of time while a tub is being filled.
FIG. 2 illustrates more particularly the lifting structure 80 of the preferred embodiment of the invention which enables both the remote reservoir tub to be raised into position and the bathing basket 56 to be adjusted by height. Specifically, the preferred embodiment includes two lifter stands 34 each of which includes a foundation 36. The foundation 36 includes feet 38 which provides stability to the lifter stand. Cylinder 40 is formed in the foundation 36 and a piston structure including a piston rod 42 having a piston head (not shown) on the lower end thereof is fitted with the cylinder 40. A pump 44 provides hydraulic fluid to opposing sides of the piston head on the piston rod 42 to cause the piston rod 42 to raise and lower within the cylinder 40.
Attached to the upper end of the piston rod 42 is a bracket 46 which raises and lowers with the raising and lowering of the piston rod 42 in response to the hydraulic pressure applied to the piston head. The two lifter stands 34 are mounted on a base 83 which distributes the weight of the apparatus and provides leverage to prevent tilting of the lifter stands. Stably and securely attached to the base 83 are guide posts 84 for the upper housing 16' and guide posts 85 for the remote reservoir 54. The posts 84 are stably mounted to the base 83 of Applicant's invention so as to control the movement of the upper housing 16' along an up and down path. Integrally attached to the upper housing 16' are sleeves 48 which journal along posts 84 so as to provide guidance and stability for the raising and lowering of the upper housing 16'. The posts 85 are stably mounted to the base 83 so as to control movement of the remote reservoir 54 along an up and down path. Integrally attached to the remote reservoir 54 are sleeves 50 which journal along posts 85 so as to provide guidance and stability for the raising and lowering of the remote reservoir 54.
Extending perpendicularly out from each piston rod 42 is a bracket 46, one of which is fastened to the upper housing 16' to cause the raising or lowering of the housing to the desired height in response to movement of its piston rod and the other is fastened to the side of the remote reservoir 54 so as to raise and lower the remote reservoir 54 in response to movement of its piston rod 42. Since the bathing basket 56 rests on and is supported by the upper housing 16' the bathing basket 56 height is adjustable by adjusting the height of the upper housing 16'. In a more simplified version of the present invention where an upper housing is not used, the bracket 46 of the lifter responsible for the movement of the bathing basket would be directly attached to the bathing basket.
The remote reservoir 54 which can be molded or formed from panels includes opposing ends A"', and B"', a back C"', a front D"', and a bottom E"', all formed into a unitary tub open at the top and otherwise constructed to hold a quantity of liquid.
As can be seen from FIG. 4, other details of the present invention include a swivel faucet 60 which is used to fill the remote reservoir tub either through an opening 62 in the top panels F" and F' of the bathing basket 56 and the upper housing 16', respectively or directly over the bathing basket 56 top opening. This device may also be provided with a hand-held nozzle 64 connected to the water source for the faucet 60 by a flexible hose 66.
Holes 58 may be provided in the bathing basket, to improve the quickness of transfer of water into and out of the bathing basket from and to the remote reservoir respectively, water will flow through the holes from the remote reservoir into the bathing basket and vice versa as the remote reservoir is raised in position, in a nesting relationship about the bathing basket 56 or lowered from a nesting relationship. The open front of the bathing basket 56 also facilitates quick water transfer. The bathing basket may also include grab rails 68 and a head rest 70 as a convenience to the bathing patient.
The bathing basket 56 may be mounted via pivot pins 72 sitting within a slide on the upper panel of the upper housing 16' so that the bathing basket can be slid towards the front of the structure and then rotated into the position shown in FIG. 8 for cleaning.
A drain 74 (see FIG. 6) of some appropriate flexible structure to accommodate the raising and lowering of the remote reservoir 54, can be attached between an outlet port in the bottom E"' of the remote reservoir 54 and drain pipe 76 in order to drain the tub by opening valve 86 with handle 87 when the bathing process is finished.
A timer mechanism 89 may be provided whereby the timer has to be reset manually at short intervals such as two minutes or else when the timer winds down it triggers a bypass valve to open in the hydraulic cylinder holding up the remote reservoir so the remote reservoir lowers. This safety device will cause the remote reservoir to default to a lowered position if the bather or assistant is not mentally or physically able to reset the timer thereby removing the bathwater away from the bather to prevent accidental drowning. A similar type device may be used to cause the raising of the bathing basket out of the remote reservoir where the method of immersion is to lower the bathing basket into the remote reservoir.
The entire tub may be further adjusted in height relative to the floor 12 by providing a floor recessed lifting device 90. Such lifting device consists of a recessed support pan 91 formed by panels identified by letters A"", B"", C"", D"", E"" and F"" designating opposing ends A"" and B"", a back C"", a front D"", a bottom E"" and a top flange F"". Said support pan 91 is supported by flange F"" resting on floor 12. Floor E"" of support pan 91 provides support for a lifting device 90 such as a hydraulic scissor jack. The scissor jack is comprised of two hinged scissor "X" mechanisms 93, a hydraulic cylinder mechanism 94, a hydraulic pump 95 and an open platform 96. Rollers 97 are provided for the non-hinged ends of the scissor "X" mechanism to allow smooth operation as the scissor jack is raised or lowered. The upper hinge 92 of the "X" mechanism 94 is securely fastened to the open platform 96. The lower hinge 98 of the "X" mechanism 94 is securely fastened to the bottom E"" of support pan 91. Hydraulic cylinder mechanism 94 has its piston rod secured by hinged bracket 99 to the open platform 96 and has its cylinder end secured by hinged bracket 100 to the bottom E"" of support pan 91. Additionally, hydraulic pump 95 is secured to the bottom E"" of support pan 91. The design of the lifting device 90 is such that the open platform 96 is raised and lowered parallel to the floor E"" of the recessed support pan 91.
The open platform 96 matches the shape of the base 83 of the lifting structure 80 and supports the bathing system comprised by the lifting structure 80, the remote reservoir tub 54, the lower housing 16, the door 22, the upper housing 16' and the bathing basket 56. By operation of the lifting device 90, the bathing system can be lowered into the floor 12 until the top of the lower housing 16 is flush with the floor 12 and the bottom E" of the bathing basket 56 is level with the floor 12. This positioning allows the bathing system to be operated as a conventional height bathtub for either immersion type bathing or showering while standing in the bathing basket. The lifting device 90 can be raised thereby elevating the bathing system to any elevation desired up to where the top of the lower housing 16 and the bottom E" of the bathing basket 56 are at their height limit "h" of 2 to 21/2 feet high to accommodate easier access for the physically or mentally impaired bather.
Additionally, if the bathing basket 56 is positioned where its floor E" is approximately level with floor 12 and the remote reservoir tub 54 is positioned in its lowered position where it would be below the floor 12, a bather could conceivably enter the bathing basket 56 and have it lowered into a pre-filled remote reservoir tub 54 and effectively enjoy a bath in a sunken tub.
Referring to FIG. 9, the various steps of operation of the remote reservoir tub of Applicant's invention are illustrated. Step 1 shows the tub with the bathing basket in its raised position and with the remote reservoir lowered and being filled with water. The door 22 is also lowered so that the bather can enter the tub. Step 2 shows the bather sitting in the bathing basket over the lowered door 22. As can be seen from Step 2, the bathing solution in the remote reservoir can be filled to the desired height and at the desired temperature without the bather having to be in the tub or touch the water. Under this arrangement, the bather will not be scalded by water that is too hot or chilled by water that is too cold as the bathtub is being filled. Further, the remote reservoir can be filled as is shown in Step 1 of FIG. 9 while the bather is positioned in the bathing basket without the water coming in contact with the bather. Thus, as soon as the bather is in the bathing basket, the remote reservoir can be raised to effect an almost instant filling of the bathing solution in the bathing basket.
Step 3 illustrates the bather within the bathing basket and in the process of raising the door 22 to provide the bather with some support along the front of the tub and protection from falling out of the tub as he sits within the bathing basket. Of course, situating the bather within the bathing basket may involve the assistance of a nurse or nurse's aid for the mentally or physically impaired patients in hospitals and nursing homes. Once the door 22 is raised (and even if door 22 is left in the lowered position), the remote reservoir may be raised by the operator pressing a switch to provide power to the pump that activates the hydraulic system that causes the piston rod 42 of the remote reservoir lifting mechanism to raise. Raising the support lifter mechanism of the lifter stand 34 raises the bracket 46 which in turn will raise the remote reservoir into the position shown in Step 5. Step 4 shows the remote reservoir in the process of being raised.
The remote reservoir, as previously indicated, is designed to mate with the bathing basket and fit about it in a nesting relationship. However, because the bathing basket has an open front and has holes 58 in the back side of it, the water within the remote reservoir will flood immediately into the bathing basket so that the bather will be totally immersed in water practically instantly once the remote reservoir is raised. By this arrangement, the bather is not required to sit exposed in a tub while it is being filled from the normal flow through a faucet. The bather is protected against being scalded or chilled by water passing from the faucet that has not been properly adjusted, and the time spent in the bathing process can be substantially reduced.
Step 5 illustrates the patient in the tub with the remote reservoir raised into an operable position. Step 6 illustrates the danger of being in the tub if, during the course of the bath, the patient loses consciousness. Under those circumstances, the assistant would throw a switch to reverse the hydraulic pressure that is holding the raised remote reservoir in position and lower the remote reservoir into position shown in Step 8 or if the bather is unattended the bather will be unable to reset the timer and the timer will automatically trigger the lowering of the remote reservoir when it winds down. The water will drain from the bathing basket practically instantly because of the open front of the bathing basket and the holes 58 so that if the patient falls into the bathing basket in the manner illustrated in Step 6 where the bather's mouth and nose may be below water, the patient will not drown before he can be removed from the tub. Step 7 shows the remote reservoir in the process of being lowered.
As a more practical illustration of the use of the remote reservoir tub of the present invention, if during the course of the bathing process, the patient advises the bathing assistant of the need to urinate or experience a bowel movement, the bathing assistant can immediately lower the remote reservoir 54, drop the door 22, remove the patient and assist him to a toilet, and when the patient is finished and ready to return to complete his bath, the patient can reenter the bathing basket, the door can be raised and the remote reservoir which contains the patient's original bath water raised into position and the bathing process completed. In this situation, the bath tub does not have to be drained with the loss of the bathing solution, and there is no wasted time associated with having to drain the water from a tub and then refill it to complete the bathing process.
Once the bath has been completed, the bathing basket can be rotated to the position shown in FIG. 8 so that the basket itself and the remote reservoir can be cleaned and disinfected for the next patient.
It would be possible to construct Applicant's remote reservoir tub so that the open front bathing basket itself can be lowered into a tub of bathing water and then raised to remove the patient after the bathing process is completed. However, such a configuration is less desired because it requires the bathing assistant to stoop over to a lower position to assist in the bathing process. However, such a structure would be usable in those circumstances where the bather has some difficulty getting in and out of a tub but does not require assistance in the bathing process, such as for obese bathers or the like. In such a structure, a lifter mechanism would be connected to the upper housing supporting the bathing basket to move the bathing basket relative to a stationary reservoir of bathing solution so that when the bathing basket with its open front is raised, the patient can enter it and press a button causing the bathing basket to lower into the bathing solution.
Although there have been described particular embodiments of the present invention of a new and useful Telescoping Bathtub Assembly, it is not intended that such references be construed as limitations upon the scope of this invention except as set forth in the following claims. Further, although there have been described certain dimensions used in the preferred embodiment, it is not intended that such dimensions be construed as limitations upon the scope of this invention except as set forth in the following claims. | A bathing tub including a bathing basket with an open front with a seating area, a back and opposing ends. The seating area can be adjusted in height and then fixed at a level approximately buttock high above a support surface so that a bather can easily slide into the seating area of the basket from a standing position through the open front. Once the bather is in the basket, a front rail is moved into a closing position to provide the bather with some support across the front of the basket and to prevent the bather from falling out of the basket. Next, a remote reservoir which has been pre-filled with a bathing liquid, usually body temperature bathing water, is raised and surrounds the bathing basket or the bathing basket is lowered into the remote reservoir to accomplish the same effect. The water will flow at a rapid pace into the bathing basket and the bather will thus be quickly immersed in water that has been pretempered to the desired temperature to any level of immersion desired. At any time during the bathing process, the side access bathing basket may be adjusted to a perfect height for a bathing assistant to attend to the bather without having to bend over and place strain on the assistant's back. | 0 |
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application is a division of U.S. patent application Ser. No. 14/205,183, filed Mar. 11, 2014, entitled “INTERMITTENT MOLTEN METAL DELIVERY”, which claims the benefit of U.S. Provisional Patent Application No. 61/777,574, filed Mar. 12, 2013, entitled “INTERMITTENT MOLTEN METAL DELIVERY”, the contents of which are incorporated herein by reference in its entirety.
FIELD OF THE INVENTION
[0002] The present invention relates to automated processes that dynamically control rate of delivery of molten metal to a mold during a casting process.
BACKGROUND OF THE INVENTION
[0003] At the beginning of an ingot cast, such as in an aluminum casting process, it is common in the first 300 mm of the cast for metal meniscus to contract and pull away from the mold on the short faces and corners. This phenomenon can occur for various reasons.
[0004] First, there can be inadequate metal flow into the corner and short face, which allows the metal to cool and pull away from the mold surface. Typically this inadequate flow is rectified by designing metal distribution systems which preferentially redistribute metal into these areas or by minimizing butt curl, which has in a roundabout way the tendency to restrict metal flow to the corner and short face.
[0005] Second, there can be excessive liquid molten-to-mold interface surface tension, which is typically an aspect of the alloy being cast. Alloys which can experience this problem include Aluminum alloys of Magnesium and/or Lithium. In some cases these alloys can be modified by surface active elements, such as, for example, Strontium, Calcium and Beryllium.
[0006] Third, there can be excessively tight corner radii. This problem can sometimes be resolved by using more liberal radii, but with a compromise of ingot scalping and hot line edge recovery. Generally, compromises made for start of the cast dynamics and recovery affect the total ingot recovery negatively in the hotline, where millions and millions of pounds are lost each year.
[0007] If such compromises are not made, overall ingot recovery is affected along with the inherent EHS aspect of metal dribbling into the mold to meniscus gap that can potentially create a butt hang-up, which can in turn cause a severe ingot explosion.
[0008] In some conventional processes, during curl, 150-250 mm into the cast, operators are continually on the casting table to make sure that the mold to meniscus gap is continually filled. From time to time they intervene and mechanically pull the metal control pin, or shake the pin-bag, to allow a sudden disruption to the metal level system to statically overcome the surface tension effect and “fill in” the corner or short face gap.
BRIEF SUMMARY OF THE INVENTION
[0009] The following presents a simplified summary of some embodiments of the invention in order to provide a basic understanding of the invention. This summary is not an extensive overview of the invention. It is not intended to identify key/critical elements of the invention or to delineate the scope of the invention. Its sole purpose is to present some embodiments of the invention in a simplified form as a prelude to the more detailed description that is presented later.
[0010] Certain embodiments of the invention solve some or all of these problems by using dynamic metal level variation or oscillation (such as by, for example, pulsing the pin or by variation of the metal-level control setpoint) during the mold fill and transient portion of the cast. It has been found that the resulting oscillating metal level, among other things, keeps metal flowing, thus overcoming the “cold corner” effect described above. Among other advantages of certain embodiments, operators no longer need to be on the table in order to overcome such effects, and corner radii compromises are less necessary or obviated.
[0011] For a fuller understanding of the nature and advantages of the present invention, reference should be made to the ensuing detailed description and accompanying drawing.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] Various embodiments in accordance with the present disclosure will be described with reference to the drawings, in which:
[0013] FIG. 1 is a schematic representation of a direct chill casting apparatus as it appears toward the end of a casting operation, according to an embodiment of the invention;
[0014] FIG. 2 is a schematic representation of a digitally and programmably implemented controller according to an embodiment of the invention; and
[0015] FIG. 3 is a pin pulse trend chart in connection with a process conducted according to an embodiment of the invention.
DETAILED DESCRIPTION OF THE INVENTION
[0016] In the following description, various embodiments will be described. For purposes of explanation, specific configurations and details are set forth in order to provide a thorough understanding of the embodiments. However, it will also be apparent to one skilled in the art that the embodiments may be practiced without the specific details. Furthermore, well-known features may be omitted or simplified in order not to obscure the embodiment being described.
[0017] The following description will serve to illustrate certain embodiments of the present invention further without, at the same time, however, constituting any limitation thereof. On the contrary, it is to be clearly understood that resort may be had to various embodiments, modifications, and equivalents thereof which, after reading the description herein, may suggest themselves to those skilled in the art without departing from the spirit of the invention.
[0018] FIG. 1 is a simplified schematic vertical cross-section of an upright direct chill casting apparatus 10 , such as is appropriate in connection with certain embodiments of the invention, at the end of a casting operation. Such molds and portions thereof are disclosed in U.S. Pat. No. 8,347,949 issued Jan. 8, 2013 to Anderson, et al. (hereinafter “Anderson”) and U.S. Pat. No. 4,498,521 issued Feb. 12, 1985 to Takeda, et al. (“Takeda”), which patents are incorporated herein by this reference. Takeda also discloses processes for conducting casting which may be appropriate for certain embodiments of this invention. With reference to FIG. 1 , the apparatus includes a direct chill casting mold 11 , preferably of rectangular annular form in top plan view but optionally circular or of other shape, and a bottom block 12 that is moved gradually vertically downwardly by suitable support means (not shown) during the casting operation from an upper position initially closing and sealing a lower end 14 of the mold 11 to a lower position (as shown) supporting a fully-formed cast ingot 15 . The ingot is produced in the casting operation by introducing molten metal into an upper end 16 of the mold through a vertical hollow spout 18 or equivalent metal feed mechanism while the bottom block 12 is slowly lowered. Molten metal 19 is supplied to the spout 18 from a metal melting furnace (not shown) via a launder 20 forming a horizontal channel above the mold.
[0019] The spout 18 encircles a lower end of a control pin 21 that regulates and can terminate the flow of molten metal through the spout. In one embodiment, a plug such as a ceramic plug forming a distal end of the pin 21 is received within a tapered interior channel of the spout 18 such that when the pin 21 is raised, the area between the plug and open end of the spout 18 increases, thus allowing molten metal to flow around the plug and out the lower tip 17 of the spout 18 . Thus, flow and rate of flow of molten metal may be controlled precisely by appropriately raising or lowering the control pin 21 . In addition to the structures shown in Anderson, spout 18 and pin 21 combinations that accomplish such purposes are also disclosed in U.S. Pub. No. 2010/0032455 published Feb. 11, 2010 to James, which publication is incorporated herein by this reference. Any desirable structure or mechanism may be used for control of flow of molten metal in to the mold. For convenience, the terms “conduit,” “control pin” and “command signals” that control position of the control pin relative to the conduit are utilized in this document to refer to any mechanism or structure that is capable of regulating flow or flow rate of molten metal into the mold by virtue of command signals from a controller; accordingly, reference in this document (including the claims) to providing command signals to a control pin positioner to regulate molten metal flow or flow rate into a mold will be understood to mean providing command signals to an actuator of whatever type to control flow or flow rate of molten metal into the mold in whatever manner and using whatever structure or mechanism.
[0020] In the structure shown in FIG. 1 , the control pin 21 has an upper end 22 extending upwardly from the spout 18 . The upper end 22 is pivotally attached to a control arm 23 that raises or lowers the control pin 21 as required to regulate or terminate the flow of molten metal through the spout 18 . During the casting operation, the control pin 21 is sometimes momentarily held in a raised position by manually grabbing and raising the pin holder 22 , which is attached to the pin 21 , so that molten metal may run freely and quickly through the spout 18 and into the mold 11 . For casting, the launder 20 and spout 18 are lowered sufficiently to allow a lower tip 17 of the spout to dip into molten metal forming a pool 24 in the embryonic ingot to avoid splashing of and turbulence in the molten metal. This minimizes oxide formation and introduces fresh molten metal into the mold. The tip may also be provided with a distribution bag (not shown) in the form of a metal mesh fabric that helps to distribute and filter the molten metal as it enters the mold. At the completion of casting, the control pin 21 is moved to a lower position where it blocks the spout and completely prevents molten metal from passing through the spout, thereby terminating the molten metal flow into the mold. At this time, the bottom block 12 no longer descends, or descends further only by a small amount, and the newly-cast ingot 15 remains in place supported by the bottom block 12 with its upper end still in the mold 11 .
[0021] Apparatus 10 can include a metal level sensor 50 whose structure and operation is conventional (unlike the sensor 50 described in Anderson, which is connected to an actuator 51 to allow the Anderson sensor to operate in a particular way in order to perform particular processes disclosed and claimed in Anderson). For example, sensor 50 can be structured and operate in the manner in which the float and transducer are structured and operate as disclosed, for example, in Takeda FIG. 1 and column 6, lines 21-52, among other places in Takeda. Alternatively, sensor 50 could be a laser sensor or another type of fixed or movable fluid level sensor having desired properties for accommodating molten metal. During the cavity filling operations, the information from sensor 50 can be fed to the controller 52 . The controller 52 can use that data among other data to determine when the control pin 21 is to be raised and/or lowered by actuator 54 so that metal may flow into the mold 11 to fill a partial cavity, i.e. when the depth of the predetermined cavity reaches a predetermined limit. Thus, the sensor 50 and actuator 54 are coupled with controller 52 , as shown in FIG. 1 , to allow information from sensor 50 to be used in connection with positioning of control pin 21 under control of actuator 54 and thereby control flow and/or flow rate of metal into the mold 11 . In a preferred embodiment, controller 52 is a proportional-integral-derivative (PID) controller, which may be a conventional PID controller, or a PID controller that is implemented as desired digitally and programmably.
[0022] FIG. 2 is an example of a controller 210 that is implemented digitally and programmably using conventional computer components, and that may be used in connection with certain embodiments of the invention, including equipment such as shown in FIG. 1 , to carry out processes of such embodiments. The controller 210 includes a processor 212 that can execute code stored on a tangible computer-readable medium in a memory 218 (or elsewhere such as portable media, on a server or in the cloud among other media) to cause the controller 210 to receive and process data and to perform actions and/or control components of equipment such as shown in FIG. 1 . The controller 210 may be any device that can process data and execute code that is a set of instructions to perform actions such as to control industrial equipment. Controller 210 can take the form of a digitally and programmably implemented PID controller, a programmable logic controller, a microprocessor, a server, a desktop or laptop personal computer, a laptop personal computer, a handheld computing device, and a mobile device.
[0023] Examples of the processor 212 include any desired processing circuitry, an application-specific integrated circuit (ASIC), programmable logic, a state machine, or other suitable circuitry. The processor 212 may include one processor or any number of processors. The processor 212 can access code stored in the memory 218 via a bus 214 . The memory 218 may be any non-transitory computer-readable medium configured for tangibly embodying code and can include electronic, magnetic, or optical devices. Examples of the memory 218 include random access memory (RAM), read-only memory (ROM), flash memory, a floppy disk, compact disc, digital video device, magnetic disk, an ASIC, a configured processor, or other storage device.
[0024] Instructions can be stored in the memory 218 or in processor 212 as executable code. The instructions can include processor-specific instructions generated by a compiler and/or an interpreter from code written in any suitable computer-programming language. The instructions can take the form of an application that includes a series of setpoints, parameters for the casting process, and programmed steps which, when executed by processor 212 , allow controller 210 to control flow of metal into a mold, such as by using the molten metal level feedback information from sensor 50 in combination with metal level setpoints and other casting-related parameters which may be entered into controller 210 to control actuator 54 and thereby position of pin 21 in spout 18 in the apparatus shown in FIG. 1 for controlling flow and/or flow rate of molten metal into mold 11 .
[0025] The controller 210 includes an input/output (I/O) interface 216 through which the controller 210 can communicate with devices and systems external to the controller 210 , including sensor 50 , actuator 54 and/or other mold apparatus components. Interface 216 can also if desired receive input data from other external sources. Such sources can include control panels, other human/machine interfaces, computers, servers or other equipment that can, for example, send instructions and parameters to controller 210 to control its performance and operation; store and facilitate programming of applications that allow controller 210 to execute instructions in those applications to control flow of metal into a mold such as in connection with the processes of certain embodiments of the invention; and other sources of data necessary or useful for controller 210 in carrying out its functions to control operation of the mold, such as mold 11 of FIG. 1 . Such data can be communicated to I/O interface 216 via a network, hardwire, wirelessly, via bus, or as otherwise desired.
[0026] FIG. 3 shows a pin pulsing trend chart for one direct chill aluminum casting process conducted in accordance with one embodiment of the invention. The chart shows actual metal level (numeral 310 ); metal level setpoint ( 312 ), the command to the pin positioner (from the PID algorithm in the controller)( 314 ), and actual pin positioner position feedback ( 316 ). (The vertical scale in this graphic corresponds to the metal level setpoint 312 .) Pulsing started at a cast length of 50 mm, and remained active for the duration until the cast ended at 500 mm.
[0027] In the embodiment shown in FIG. 3 , during pulsing, the actual analog signal to the pin is in the form of square pulses set to 100%, bypassing the command signal from the PID algorithm. This square wave is not apparent in FIG. 3 , but it corresponds generally in time and duration to time and duration of pin positioner pulses 316 . The fact that the analog signal bypasses the command signal from the PID algorithm is apparent, as shown by the metal level being consistently above the setpoint for about the first 50% of the time after pulsing commences. Under those conditions, the PID controller would ordinarily output a 0% open pin position command in an attempt to stop metal from flowing into the mold. In actual application according to some embodiments, this would not be allowed since an open pin position command that is below a predetermined value for a predetermined period of time, such as 0% open pin position or below 1% open pin position for 5 seconds, constitutes an ingot hangup condition and activates an ingot hangup alarm. An ingot hangup is where the ingot gets stuck in the mold, which can occur due to excessive butt curl during the early part of the cast between about 50 and 400 mm of cast length. The conditions that constitute the ingot hangup and that activate the ingot hangup alarm can vary somewhat between plants, and normally result in an automatic abort of the cast. However, during the process charted in FIG. 3 , this alarm was disabled temporarily.
[0028] In the particular embodiment charted in FIG. 3 , the pulsing frequency varies over time. This variation is due to the pulsing algorithm restricting pulsing to occur only if the actual metal level is no higher than 1 mm above setpoint. Also, in this particular example the pulsing frequency is set to 3 pulses/minute (or less if metal level conditions are not met).
[0029] Although FIG. 3 relates to one process according to one embodiment of the invention, it is not necessarily representative of certain other embodiments, which could be performed as follows:
[0030] 1. In some embodiments, control pin pulsing occurs in a manner that modulates flow or flow rate of molten metal through the conduit such that the level of molten metal in the mold remains in a molten metal level range of between 5 mm above and 3 mm below, inclusive, the metal level setpoint, and preferably in a molten metal level range of between 3 mm above and 1 mm below, inclusive, the metal level setpoint. Preferably, in the preferred molten metal level range, the metal level will rise to about 3 mm above setpoint as a result of each pulse, and between pulses (prior to the next pulse) will typically drop to about 1 mm below setpoint under the control of the PID algorithm as a result of undershoot.
[0031] 2. In some embodiments, pulsing occurs at a frequency of 3-4 pulses/min, inclusive, or a minimum of 15-20 seconds between pulses, inclusive.
[0032] 3. In some embodiments, pulsing will be allowed to occur only if the actual metal level is at or below the metal level setpoint AND the command signal to the pin positioner is above a predetermined value (for example greater than 5% open pin position, such that the hangup alarm logic will not be adversely affected).
[0033] 4. In some embodiments, during pulsing, the actual command signal to the pin positioner is preferably set to 100% open pin position for a duration of preferably about 3 seconds, which period may be larger or smaller, after which it will return to control under the PID algorithm. The pin positioner takes time to open/close and thus can only open to between 30% and 50% open in 3 seconds. In some embodiments, depending on characteristics of the particular control pin positioner at issue, the command signal to the pin positioner is set to open pin position for a longer or shorter period that is at least partially a function of how quickly the pin positioner can open and/or close.
[0034] 5. In some embodiments, pulsing will begin at a cast length of 50 mm.
[0035] 6. In some embodiments, pulsing will end when the cast length reaches, preferably, between 400 and 500 mm.
[0036] Pin pulsing can be accomplished in any number of alternative ways according to various embodiments of the invention. For instance, pulsing could be accomplished by time-varying the metal level setpoint, or by time-varying sinusoidally the pin positioner command signal about the PID control value (by adding a sinusoidal signal to the PID output control value).
[0037] Other variations are within the spirit of the present invention. Thus, while the invention is susceptible to various modifications and alternative constructions, certain illustrated embodiments thereof are shown in the drawings and have been described above in detail. It should be understood, however, that there is no intention to limit the invention to the specific form or forms disclosed, but on the contrary, the intention is to cover all modifications, alternative constructions, and equivalents falling within the spirit and scope of the invention, as defined in the appended claims.
[0038] The use of the terms “a” and “an” and “the” and similar referents in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The terms “comprising,” “having,” “including,” and “containing” are to be construed as open-ended terms (i.e., meaning “including, but not limited to,”) unless otherwise noted. The term “connected” is to be construed as partly or wholly contained within, attached to, or joined together, even if there is something intervening Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”) provided herein, is intended merely to better illuminate embodiments of the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.
[0039] Preferred embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Variations of those preferred embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventors expect skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.
[0040] All references, including publications, patent applications, and patents, cited herein are hereby incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein. | Automated processes that dynamically control rate of delivery of molten metal to a mold during a casting process. Such automated processes can use dynamic metal level variation, control pin pulses and/or oscillation during the mold fill and transient portion of the cast. It has been found that such pulses keep metal flowing in a manner that addresses problems, particularly at the beginning of an ingot cast, associated with metal meniscus contracting and pulling away from the mold on the short faces and corners. | 1 |
STATEMENT REGARDING PRIOR DISCLOSURES BY THE INVENTOR OR JOINT INVENTOR
[0001] The inventor did not disclosed the invention herein prior to the 12 month period preceding the filing of this nonprovisional application.
BACKGROUND OF THE INVENTION
[0002] (1) Field of the Invention
[0003] The present invention relates to a method and an apparatus for sanitizing water for human consumption. This method and apparatus has a number of applications such as disinfection of water for personal and commercial purposes, such as purification of water for pools and spas and other recreational activities, purification of drinking water, and purification of water for use in commercial establishments.
[0004] (2) Description of Related Art
[0005] In many areas of the undeveloped world, there is a need for cheap, sustainable water treatment. The water treatment system or method must be portable so that it can be distributed into remote regions around the globe. The World Health Organization estimates that globally, at least 1.8 billion people use a drinking-water source contaminated with feces. Contaminated water can transmit diseases such as diarrhea, cholera, dysentery, typhoid, and polio. Following natural disasters, many people in less developed areas of the world, are unable to find safe water for drinking, cooking, and bathing. A portable, cheap, and easy to use method and apparatus is needed to rid water of harmful bacteria and viruses. This method and apparatus should be easy to use so that people with little or no education can perform the necessary steps. Typically, water is disinfected using one or more of the following methods: boiling, ultraviolet radiation, ozonation, reverse osmosis, and chlorination. Boiling requires the input of firewood and creates large quantities of smoke, that can damage the environment and be harmful if inhaled. Both ultraviolet radiation and ozonation require expensive equipment and may require special training to operate and maintain the equipment. Reverse osmosis requires pre-filtration and is expensive to perform and maintain. Chlorination is relatively cheap, easy to perform, and protects the water against contamination following disinfection.
[0006] Numerous devices and methods have been disclosed that sanitize and purify water for human use. Namespetra et al. (U.S. Pat. No. 7,959,872 B2) discloses a pitcher device including extruded carbon sheet or granulated activated carbon to filter unpurified, gravity-fed water. This device requires the carbon to be positioned above the water level maintained within the pitcher and would not function to disinfect the quantities of water necessary for a family's daily needs. Namespetra et al. (U.S. Pat. No. 7,767,168 B2) discloses a sanitation system that sanitizes water by the incorporation of ozone into the water, which is circulated by a pump. Barnes (U.S. Pat. No. 8,075,784 B1) and Barnes (U.S. Pat. No. 7,883,622 B1) disclose the use of the combination of chlorine and ozone to sanitize water. The Barnes devices require high oxidation potentials from ozone, which is generated with an ultraviolet ozone generator. An ozone generator adds costs and complexity to the treatment of water. Additionally, the Barnes devices require one or more venturi to increase the flow of water and solutes through the water treatment system. Vandenbelt et al. (US 2008/0314808 A1) discloses a hand-held pitcher device that filters small batches of water using ozone generated by a UV line radiator inside the pitcher. Although hand-held pitcher devices are highly portable and easy to use, they are not able to effectively purify sufficient quantities to meet a typical family's daily water needs. Because ozone has a very short half life, water disinfected using ozone may be quickly re-contaminated. Thus, the devices utilizing ozonation are not effective in providing adequate water supplies to impoverished regions.
[0007] Garcia (U.S. Pat. No. 6,814,877 B2) combines ozonation and chlorination to purify water for swimming pools, ponds, aquatic mammal tanks, and spas or fountains. Garcia employs chlorine dioxide as a disinfectant. This method is not suitable for drinking water because just one half a drop of chlorine dioxide can cause severe nausea, diarrhea and vomiting. McCague (U.S. Pat. No. 8,273,254 B2) discloses a spa sanitation system that includes an ozone generator, a chlorine generating cell to generate chlorine and other sanitizing agents for sanitizing the water, a calcium remover bag, and adding salt to the water. This system is built into a whirlpool and requires a contact chamber of 8 to 10 feet in length. Thus, this method is not portable, and is unsuitable for use in remote areas of the world.
[0008] Swartz et al. (US 2011/025760 A1) discloses a electrolyzing system for electrolyzing a brine solution of water and an alkali salt to produce acidic electrolyzed water and alkaline electrolyzed water. The invention of Swartz et al. includes a series of ion permeable membranes that concentrate ions in water to produce acidic sanitizer and, separately, base cleaners. Water is drawn into the top of the device, ions from a brine solution are concentrated in the water, acidic and basic solvents drain separately from the bottom of the device. The invention of Swartz et al. could not be used to produce drinking water or to sanitize water for a pool or spa because it produces acidic and basic solvents that are not suitable for human consumption. The device of Miller et al. (U.S. Pat. No. 4,121,991) discloses an electrolytic cell for the treatment for the purification and sterilization of water for human use. Water enters the Miller et al. device from the bottom and exits from the top of the device. Water entering the Miller et al. device must have been previously chlorinated to a level of 3 ppm chloride ions. This device would not purify or sanitize water that had not been previously chlorinated or sanitized. Thus, this device requires multiple steps which add to its complexity and, therefore, limit its usage by unsophisticated users and limits its use in remote areas across the undeveloped world.
[0009] McGuire (U.S. Pat. No. 6,368,472 B1) discloses an apparatus for generating chlorine and ozone for water disinfection wherein the apparatus is relatively portable and the individual parts are somewhat inexpensive. McGuire discloses a anolyte reaction chamber attached to a anode plate and a catholyte reaction chamber attached to a cathode plate. The anolyte and catholyte plates have at least one sealing gasket interposed between them so as to form a reaction chamber wherein electrolysis chemicals are produced. These electrolyte chemicals are then pumped through water for an hour or more to disinfect and purify the water. This device has many disadvantages including, but not limited to: there are a number of individual parts that must be obtained and assembled correctly to create the device, all of these parts may not be obtainable in many undeveloped areas, assembly of the device can be confusing and difficult for someone lacking basic plumbing or mechanical skills, the device only accepts DC power, the device must be rotated about its horizontal axis so that the cathode chamber is rotated downward in order to prevent the accumulation of hydrogen gas within the device, byproducts of the device include bleach and hydrogen peroxide that must be disposed of properly, the pump must be placed within a drum, cistern, or tank of sufficient size, the reaction chamber must be secured to a tree, post, or some other solid object, and the device can only be operated outside or in a well ventilated area. These disadvantages limit the use of the McGuire device. A new apparatus and method is needed that eliminates these disadvantages.
[0010] Typically, water treatment methods and systems are costly to operate, large in size, require high inputs of energy, and require the addition of chemicals, which are often caustic, to function properly A need exists for a water disinfection method and apparatus that is cheap, easy to transport, easy to install, easy to operate, that doesn't require special, caustic chemicals to operate, doesn't produce caustic chemicals requiring disposal. The Water Sanitizing System meets these needs and will enable the poorest people throughout the world to clean and disinfect their water supply at an extremely low financial cost without the addition of either toxic chemicals or costly energy resources. And, this method and apparatus may be utilized by spa, fountain, and pool owners to disinfect water.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
[0011] FIG. 1 illustrates an exterior, side view of the Water Sanitizing System.
[0012] FIG. 2 illustrates an exterior, side view of the lid.
[0013] FIG. 3 illustrates an exterior, side view of the canister.
[0014] FIG. 4 illustrates an exploded, side view of the lid, heat exchanger and electrical wires.
[0015] FIG. 5 illustrates a front view of the electrode.
[0016] FIG. 6 depicts an exploded, side view of the electrode assembly.
[0017] FIG. 7 depicts an exterior, side view of the Water Sanitizing System with circular electrodes.
[0018] FIG. 8 depicts an exploded, side view of the lid, electrode wires, optional thermostat, and optional aerator of the circular electrode embodiment.
[0019] FIG. 9 illustrates an exploded, side view of the lid, canister, electrode assembly, electrical wires, and heat exchanger for the circular-shaped electrode embodiment.
[0020] FIG. 10 depicts a side view of the sigmoid-shaped heat exchanger.
[0021] FIG. 11 depicts an exploded, side view of the circular electrode embodiment.
DETAILED DESCRIPTION OF THE INVENTION
[0022] The invention is described in detail in the following paragraphs with reference to the attached drawings. Throughout this detailed description of the invention, the disclosed embodiments and features are to be considered as examples, rather than being limitations to the invention. Modifications to particular examples within the spirit and scope of the present invention, set forth in the appended claims, will be readily apparent to one of ordinary skill in the art. Further, reference to various embodiments of the disclosed invention does not mean that all claimed embodiments or methods must include every described feature. The various disclosed embodiments and features of the invention may be used separately or together, and in any combination. Terminology used herein is given its ordinary meaning consistent with the exemplary definitions set forth below.
[0023] FIGS. 1 through 6 depict an embodiment of the Water Sanitizing System with a linear electrode assembly and FIGS. 7 through 11 depict the device with a circular electrode assembly.
[0024] FIG. 1 illustrates an exterior, side view of the Water Sanitizing System. The Water Sanitizing System may be coupled to a cistern holding water. Water from the cistern may be pumped via a common water pump into the device for sanitizing. Lid 16 is shown attached to canister 20 . Port 4 located on lid 16 may be utilized to anchor electrical wires 58 and 62 (shown in FIG. 4 ) to the lid. Port 2 of lid 16 is shown securing the heat exchanger tube 36 (shown in FIG. 4 ) into the correct position within the device. Water flows into canister 20 for sterilizing via intake fitting 44 . A portion of water entering the intake fitting 44 is diverted through the diverter 42 into water circulator 3 , and to the heat exchanger tube 36 . Water circulator 3 connects diverter 42 to mixer fitting 52 and allows water to bypass heat changer 36 and exit the device via outlet fitting 56 . The heat exchanger allows heat generated in canister 20 to be absorbed by the cooler water passing through heat exchanger tube 36 (shown in FIG. 4 ) and to exit canister 20 via mixer fitting 52 , which mixes the heated water in the heat changer tube 36 with water exiting canister 20 through outlet fitting 56 . Long and short electrical wires, 58 and 62 (shown in FIG. 4 ) respectively, run the length of electrode frame 106 , make a 90° turn before running the width of electrode frame 106 , make a second 90° turn before running along the width of electrode frame 106 , and terminating at the face of negative electrode 104 and positive electrode 70 , respectively. Positive electrode 70 is shown with screws 82 and nuts 48 which are used secure the parts of the device together and to space the distance that electrodes 70 and 104 are from the electrical wires and from electrode frame 106 . Optional thermostat sensor 134 is shown in FIG. 1 .
[0025] FIG. 2 illustrates an exterior, side view of lid 16 . Lid 16 may include inlet 11 (shown in FIG. 4 ) that allows contaminated water to enter the device and outlet 10 that allows purified and sanitized water to exit the device. Lid 16 may include brim 14 which is gripped by a user when screwing lid 16 onto and off of canister grip 18 (shown in FIG. 3 ) via tapered threads 16 . Ports 2 and 8 may be utilized to circulate water through the heat exchanger ( 34 , 36 , 38 , and 40 , shown in FIG. 4 ). The heat exchanger ( 34 , 36 , 38 , and 40 , shown in FIG. 4 ) should be composed of or coated with a non-conductive material so that it does not interact with the electrodes in the device. Port 4 may be used to anchor and attach the electrical wires ( 58 , 60 , 62 , and 64 , shown in FIG. 4 ) that power the device. Port 6 may be used to mount or anchor the device in a fixed position. For example, the device may be anchored to a cistern via port 6 . The device may include hole 7 to allow excess gas formed during the sanitization process to vent from canister 20 (shown in FIG. 1 ).
[0026] Canister 20 is depicted in FIG. 3 . Canister 20 may be composed of any clear material that allows a user to view the internal components of the device, such as glass, plastic, poly propylene or other suitable material. Canister 20 should be composed of a material that is resistant to corrosion and microbial growth. Additionally, canister 20 must be composed of a material that is resistant to heat, chlorine, hydroxide, ozone and contaminated water. It is imperative that canister 20 be sufficiently clear so that a user can observe the sanitizing process to ensure that the device is working properly. Water and table salt are mixed to form a brine. The user may mix as little as 15 grams of salt per liter of brine to as much as 227 grams of salt. The brine is contained within canister 20 . The salt in the water is converted via electrolysis to chlorine gas, hydroxide gas, and ozone. These gases mix with the contaminated water fed to the device sanitizing said water. Canister 20 may hold approximately 1 liter of brine solution.
[0027] FIG. 4 illustrates an exploded, side view of lid 16 , heat exchanger ( 34 , 36 , 38 , and 40 ), and electrical wires ( 58 , 60 , 62 , and 64 ). Both the heat exchanger ( 34 , 36 , 38 , and 40 ) and the electrical wires ( 58 , 60 , 62 , and 64 ) anchor into lid 16 . The heat exchanger ( 34 , 36 , 38 , and 40 ) may anchor into ports 2 and 6 . The heat exchanger ( 34 , 36 , 38 , and 40 ) is comprised of a hollow, medium pressure copper-nickel tube. The heat exchanger ( 34 , 36 , 38 , and 40 ) must be composed of a corrosion-free material. The heat exchanger ( 34 , 36 , 38 , and 40 ) reduces the water temperature within canister 20 by circulating water from the cistern through the exchanger ( 34 , 36 , 38 , and 40 ). Heat created during the sanitizing process are transferred to the cooler temperature of the water entering inlet 11 , which prevents a significant increase in the temperature of the brine. Water enters inlet 11 through fitting 44 . Fitting 44 is a hollow tube that may be composed of rubber, plastic or any hard material resistant to heat, ionic gases, and water. Fitting 44 includes diverter 42 . Diverter 42 is a hollow protrusion that diverts water entering inlet 11 via fitting 44 into the heat exchanger ( 34 , 36 , 38 , and 40 ). The heat exchanger ( 34 , 36 , 38 , and 40 ) is a hollow tube formed to fit along the electrode assembly 17 (shown in FIG. 6 ). The heat exchanger ( 34 , 36 , 38 , and 40 ) is comprised of the following segments: a short horizontal projection 40 , two vertical projections 35 and 36 , a horizontal base projection 38 , and a horizontal lid projection 34 . The short horizontal projection 40 connects the diverter 42 to a vertical projection 35 . Vertical projections 35 and 36 run the vertical length of the electrode assembly 17 . Vertical projection 35 connects to the horizontal base projection 38 that runs the width of the electrode assembly 17 . Horizontal base projection 38 connects to the second vertical projection 36 . The second vertical projection 36 connects to the horizontal lid projection 34 , which feds the water to port 8 on the lid 16 .
[0028] Water flowing through port 8 , flows into mixer fitting 52 . Mixer fitting 52 is a hollow projection stemming from outlet fitting 56 . Outlet fitting 56 is a hollow fitting that connects to outlet port 10 of lid 16 . Water heated due to the transfer of heat from the electrode assembly 17 to the water traversing the heat exchanger ( 34 , 36 , 38 , and 40 ) exits the device via outlet fitting 56 and flows back to the water cistern.
[0029] FIG. 4 depicts the attachment of chlorometer 30 to the device. Chlorometer 30 may be attached to the horizontal lid projection 34 via chlorometer fitting 32 . Chlorometer fitting 32 is a hollow tube that is sized to connect to the chlorometer 30 to port 8 . Chlorometer 30 is a commercially available product that quantifies the concentration of chlorine in water. Chlorometer 30 may be installed along the heat exchanger ( 34 , 36 , 38 , and 40 ) because it measures the chlorine concentration of water being pumped from the cistern. Chlorometer 30 must be connected to the DC power source that powers the device. Chlorometer 30 allows the user to determine if the device has been sufficiently chloronated, and hence, adequately sanitized and killed suspected microbial contamination. Chlorometer 30 can be configured to shut off power to the device when the desired chlorine concentration is obtained in the water. If salt water is used with the device, then excess salt may not need to be added. If using fresh water in the Water Sanitizing System, salt will need to be added to water to produce a brine solution. For example, a user may add 227 grams or a cup of salt to two liters of fresh water. If a large cistern of water is to be sanitized, then the device may be scaled up to hold much more than two liters of brine solution. A final concentration of 2.0 mg/L of chlorine per fresh water must be obtained within the cistern to destroy all organism but does not provide sufficient levels of chlorine to deal with future contamination that may occur during storage and transport. A concentration of 2.5 mg/L of chlorine will destroy all organisms while leaving a concentration of 0.5 mg/L to prevent future contamination. Previous use of the device has enabled the purification of 18.9 kL of contaminated water with a level of 5 mg/L chlorine atoms with just 227 grams of salt having been mixed with 1.89 L of water. If the water is purified to a level of 5 mg/L, then the water must sit for approximately 24 hours or until the chlorine levels drop below 3 mg/L before human consumption.
[0030] The straight ends of both the long electrical wire 62 and the short electrical wire 58 fit within port 4 of lid 16 anchoring the wires into the device. A DC power source is attached to long electrical wire 62 and short electrical wire 58 to power the device. The device may be powered by any power supply as known in the art, including a DC power supply, solar panels, battery or batter charger. While the device is preferably powered by about 6 to 12 volts DC, lower voltage will power the device at a reduced rate. The device may be powered by full wave and half wave pulsed DC. However, half wave pulsed DC will reduce the rate of chlorine gas production and the rate of water sanitization. Although DC power powers the electrical wires, AC power supplied by a standard power line can be converted to DC power to power the device. Both the long and short electrical wires, 62 / 64 and 58 / 60 respectively, provide electrical power to power the electrolytic conversion of salt into chlorine gas and hydroxide. The long and short electrical wires, 62 / 64 and 58 / 60 respectively, are configured so that long wire 62 / 64 sends power to the negative or anode electrode 70 (shown in FIG. 5 and FIG. 6 ) while short wire 58 / 60 transmits power to the positive or cathode electrode 104 (shown in FIG. 6 ). The electrical charge powers the conversion of salt in the brine into Na+ and Cl− ions, hyroxide ions, and ozone. These electrolytes sanitize and purify the contaminated water moving through canister 20 .
[0031] Screw 82 is used to attach the heat exchanger ( 34 , 36 , 38 , and 40 ) to lid 16 . Screw 82 is nestled in the elbow connecting the second vertical projection 36 to the horizontal lid projection 34 . Screw 82 is anchored into tab bracket 66 via nut 48 . Tab bracket 66 includes head 68 , which is pushed into a slot on the inside face of lid 16 . Long electrical wire 64 fits snugly into tab bracket 66 . Tab bracket head 68 anchors the long electrical wire 64 into an opening on the inside face of lid 16 securing long electrical wire 64 into position along the electrode assembly 17 (shown in FIG. 6 ).
[0032] Hole 7 , if included in the device, permits the flow of exhaust gases out of the device for venting into the air. Plug 50 fits into hole 7 plugging the exhaust of gas when an optional means to exhaust excess gas is employed.
[0033] FIG. 5 depicts the positive or cathode electrode 70 . Positive electrode 70 contains a number of openings 72 that allow for the free movement of ions and brine solution through the electrode assembly 17 . Openings 72 increase the surface area for the electrolytic reaction, thus allowing a greater quantity of electrolytes to be produced. The Water Sanitizing System requires both a positive or cathode electrode 70 and a negative or anode electrode 104 (shown in FIG. 6 ). Both electrodes 70 and 114 must be equal in size and must be configured so that the mass of electrode 70 faces the mass of electrode 114 . This provides for more efficient conductivity, which enhances electrolytic production and water sanitization. Electrodes 70 and 114 must have current applied to opposing ends of the opposing electrode. For example, if the positive wire 58 connected to positive electrode 70 is placed on the top center of positive electrode 70 , then negative electrode 114 should have the negative wire 62 placed at the bottom center of the negative electrode. The positive electrode 70 generates ozone radicals and hydrogen gas, while the negative electrode 114 generates chlorine gas and hydroxide. The electrolytes migrate though the brine and the contaminated water sanitizing the water. A permeable ion membrane (shown in FIG. 6 ) is placed between the electrodes 70 and 114 . Electrodes 70 and 114 must not touch each other or the ion membrane. Electrodes 70 and 114 must be spaced an equal distance from each other and an equal distance from the ionic membrane. A non-conductive, non-corrosive washer can be used as a spacer to space the membrane equal distance between electrodes 70 and 114 . Electrodes 70 and 114 are composed of stainless steel, titanium, expanded titanium, zirconium, expanded zirconium, hafnium, expanded hafnium, niobium, expanded niobium, nickel, expanded nickel, chromium, expanded chromium, a transition metal, a metal alloy, a combination thereof, or any suitable material.
[0034] FIG. 6 illustrates the electrode assembly 17 . The electrode assembly 17 may include “I”-shaped bar 74 , positive electrode 70 , ionic membrane frame (parts 92 and 100 ), ionic membrane 96 , negative electrode 104 , electrode frame 106 , exhaust elbow 118 , and an assortment of non-corrosive screws 82 with non-corrosive nuts 48 . “I” bar 74 is a non-conductive, non-metal bar composed of plastic, or any similar material. “I” bar 74 secures positive electrode 70 into position. The Water Sanitizing System is more efficient at sanitizing contaminated water than the prior art because positive electrode 70 is not housed within a sealed chamber. “I” bar 74 contains holes 76 and 78 through which screw 82 is inserted to anchor the positive electrode 70 a set distance from the ionic membrane frame 92 . Ionic membrane frame 92 and 100 frame ionic membrane 96 on both sides of said membrane 96 . Screws 82 fit through holes 94 and 102 to secure ionic membrane 96 to the electrode frame 106 . The ionic membrane 96 allows cations, such as sodium ions, to travel from the negative or anode electrode 104 towards the positive or cathode electrode 70 while resisting the flow of positively charged species across the membrane from the positive electrode 70 to the negative electrode 104 . The ionic membrane should be the same approximate length and width of electrodes 70 and 104 . Ionic membranes capture viruses and large parties while allowing certain ions to freely pass through pores within said membrane. A number of suitable ionic membranes are commercially available. The negative electrode 104 is positioned within electrode frame 106 . Electrode frame 106 is a box created by two vertical arms that are at least as long as negative electrode 104 that are connected via an upper horizontal arm that is at least as wide as the width of electrode 104 . The electrode frame 106 is sealed on three sides using a sealant known in the art such as room temperature vulcanizing silicone. The bottom of electrode frame 108 is open. During the sanitization process, brine and water enter into the electrode frame 106 via opening 108 . The frame opening 108 dramatically increases the efficiency of chlorine gas production during sanitization and, thus, increases the rate of sanitization. Other electrolyte generators and water sanitizing systems have one or more closed anionic/cationic chambers that a reduce rate of both water sanitization and electrolyte production. Electrode frame 106 includes a number of holes 110 sized to fit screws 82 . Screws 82 may be fitted through holes 78 located on “I” bar 74 , through holes 94 located on the ionic membrane frame 92 , into holes 110 positioned on electrode frame 106 . Electrode frame 106 includes hole 114 , which is centered along the upper frame arm. Hole 114 is sized to permit the exhaust elbow 118 to fit securely into said hole 114 via tapered end 116 . Exhaust elbow 118 is hollow and includes exhaust outlet 120 . Excess gas produced in the electrode assembly is vented through exhaust elbow 118 and out exhaust outlet 120 . Water Sanitizing System devices lacking an exhaust elbow 118 may vent excess gases through hole 7 positioned on lid 16 (shown on FIG. 2 ). Additionally, if there is sufficient draw within canister 20 , external air may enter electrode frame 106 via exhaust elbow 118 .
[0035] Brine solution within canister 20 must be maintained at a level that is approximately 25 mm over the top of positive electrode 70 and negative electrode 104 for optimum performance of the device.
[0036] An optional thermostat 130 may be installed on the device to shut the device down if the temperature within canister 20 rises above a predetermined value, such as 87° C. Additionally, optional aerator 140 may be added to the device to pump air into canister 20 to facilitate the production of electrolytes and the movement of gases into and out of the device during the sanitization process.
[0037] If a user desires to sanitize a large quantity of water, then two or more Water Sanitizing System devices may be installed in a series to increase the yield of sanitized water and the rate of sanitization.
[0038] FIG. 7 depicts an external, side view of the Water Sanitizing System with circular electrodes. Contaminated water flows into intake fitting 44 on lid 16 and enters canister 2 . Water circulator 3 connects diverter 42 to mixer fitting 52 to allow for the movement of water to heat exchange tubing 152 . Heat exchange tubing 152 runs the width and length of positive electrode 176 , and may form a number of “S” or sigmoid-shaped elbows. Short electrical wire 58 is visible through canister 20 .
[0039] An exploded, side view of lid 16 , electrode wires 58 / 60 and 62 / 64 , heat exchanger ( 150 , 152 , 154 , and 156 ), electrode assembly 19 ( 170 , 172 , 174 , and 176 ), optional thermostat 130 , and optional aerator 140 of the circular embodiment is shown in FIG. 8 . Optional thermostat 130 includes sensor 134 that detects the temperature of the water/brine solution within canister 20 . Thermostat 130 is powered via the DC power supplied to connector 132 . Optional aerator 140 may be installed in the device by inserting aerator tab 142 into hole 7 . Water and brine solution are aerated as the fluid is pumped through aerator pipe 146 . Aerator 140 also operates on DC power that is supplied to the device. If aerator 140 is not used, plug 50 may be used to plug hole 7 . Long electrical wire 62 runs the length and width of positive electrode 176 (shown in FIG. 9 ) creating a long hook 64 that terminates at the top of said electrode 176 hooking onto the inside wall of the electrode 176 . Short electrical wire 58 runs the length and width of the negative electrode 170 creating a short hook 60 that terminates at the top of said electrode 170 hooking onto the inside wall of the electrode 170 . Tab brackets 66 are used to secure the long electrical wire 64 and the thermostat 130 into the inside face of lid 16 .
[0040] FIG. 9 depicts an exploded, side view of the lid, canister, heat exchanger, and electrode assembly. The long and short electrical wires ( 62 and 58 , respectively) are shown installed within a port of lid 16 . The heat exchanger ( 150 , 152 , 154 , and 156 ) connects to water diverter 42 of intake fitting 44 via tubing section 156 . The heat exchanger ( 150 , 152 , 154 , and 156 ) has two vertical sections 152 that run horizontally the width of the electrode assembly, make an 180° turn, and run the horizontal width of the electrode assembly ( 150 , 152 , 154 , and 156 ) creating a “S”-shaped pattern. Two vertical sections 152 are connected to each other via horizontal tube 154 near the bottom of canister 20 . Heat exchanger tubing 150 connects the heat exchanger ( 150 , 152 , 154 , and 156 ) to water circulator 52 of outlet fitting 56 . Electrode frame 172 seals negative electrode 170 on all sides except for the bottom, which is open to allow for the flow of water and brine into the electrode assembly 19 . Two ionic membrane filters 174 are placed against electrode frame 172 sealing the vertical surfaces of electrode frame 172 . Filters 174 create a tight seal preventing the free flow of water and brine through the vertical surfaces of the frame 172 . Positive electrode 176 is positioned outside of ionic membrane filters 174 so that filters 174 are equally spaced between electrodes 170 and 176 .
[0041] A side view of vertical section 152 of the heat exchanger ( 150 , 152 , 154 , and 156 ) and the heat exchange tubing 150 is shown in FIG. 10 .
[0042] FIG. 11 illustrates an exploded, side view of the electrode assembly 19 . Negative electrode 170 is hollow with cavity 188 for the flow of water and brine to increase the surface area of electrode 170 , which increases the electrolytic capacity of the device. Negative electrode 170 nests within electrode frame 172 . Electrode frame 172 includes hollow cavity 190 to position negative electrode 172 within the electrode assembly 19 . Two ionic membrane filters 174 with a semi-circular shape are positioned against electrode frame arms 180 to create a seal. The bottom of electrode frame 172 includes triangular ends 184 that create open channels 186 that permit the free flow of water and brine into hollow cavity 188 . Positive electrode 176 includes cavity 178 that allows it to be fitted over electrode frame 172 . This device increases the rate of sanitization and the efficiency of chlorine gas production during sanitization than what is available in the prior art.
[0043] Having thus described our invention, and the manner of its use, it should be apparent to one of average skill in the arts that incidental changes may be made thereto that fairly fall within the scope of the following appended claims, wherein I claim: | The present invention relates to a portable water purification and sanitizing apparatus and method. Due to the limited size of the apparatus and its ability to utilize DC power, the apparatus can be transported and operated in remote areas across the globe. The apparatus and method generates electrolytic products of chlorine, hydroxide and ozone that are utilized to purify and sanitize water for human consumption. | 2 |
CROSS REFERENCE TO RELATED APPLICATION
[0001] The present application is a continuation of U.S. patent application Ser. No. 14/934,794, entitled “Microfluidic Chips with Optically Transparent Glue Coating and a Method of Manufacturing Microfluidic Chips with Optically Transparent Glue Coating for a Microfluidic Device,” filed Nov. 6, 2015, which is a continuation of U.S. patent application Ser. No. 14/028,320, entitled “Microfluidic Chips with Optically Transparent Glue Coating and a Method of Manufacturing Microfluidic Chips with Optically Transparent Glue Coating for a Microfluidic Device,” filed Sep. 16, 2013, now U.S. Pat. No. 9,180,652, the entire contents of each of which is hereby incorporated by reference herein.
BACKGROUND OF THE DISCLOSURE
[0002] Field of Disclosure
[0003] The present disclosure relates generally to a method of manufacturing microfluidic chips for handling fluid samples on a microfluidic level, and, more specifically, to a method of manufacturing microfluidic chips with coating to reduce fluid diffusion and microfluidic chips with a coating to reduce fluid diffusion. The manufactured microfluidic chips can be used to perform real-time analysis, for example, polymerase chain reaction (PCR) analysis.
[0004] Discussion of the Related Art
[0005] Microfluidics can be used in medicine or cell biology researches and refers to the technology that relates to the flow of liquid in channels of micrometer size. At least one dimension of the channel is of the order of a micrometer or tens of micrometers to be considered as microfluidics. In particular, microfluidic devices are useful for manipulating or analyzing micro-sized fluid samples on microfluidic chips, with the fluid samples typically in extremely small volumes down to less than picoliters.
[0006] When manipulating or analyzing fluid samples, fluids are pumped onto the micro-channel of microfluidic chips in doses or are continuously flowed onto the micro-channel of microfluidic chips. If the fluid sample is pumped in doses, the fluid sample stays in the micro-channel of the microfluidic chip until the fluid sample is suctioned out from the micro-channel. The fluid sample can be manipulated or analyzed while being held in the micro-channel.
[0007] Alternatively, for continuous flow analysis, the fluid is pumped continuously into the micro-channel. Due to the continuous fluid pumping, the fluid sample instead flows and travels through the micro-channel and exits the micro-channel when reaches the outlet of the micro-channel. The fluid sample can be manipulated or analyzed while flowing through the micro-channel, and one can perform a biochemical reaction examination on the continuously flowing fluid sample, including treating and manipulating processes of the fluid.
[0008] Presently, microfluidic chips have micro-channels molded in PolyDiMethyiSiloxane (“PDMS”). The micro-channels then are sealed when the PDMS block is bonded to a glass slide.
[0009] FIGS. 1A-1D are perspective views of manufacturing a microfluidic chip mold according to the related art. The manufacturing of a microfluidic chip according to the related art takes a channel design and duplicates the channel design onto a photomask 10 . As shown in Figure IA, a photoresist 22 is deposited onto a semiconductor wafer 20 . As shown in FIG. 1B , the photomask 10 that reflects the channel design 12 is placed over the wafer 20 , and the wafer 20 with the mask 10 undergoes UV exposition to cure the photoresist 22 . Then, as shown in FIG. 10 , the wafer 20 with the cured photoresist 22 ′ is developed. The ‘negative’ image of a channel according to the channel design is etched away from the semiconductor wafer 20 . As shown in FIG. 1D , after all residual photoresist are removed, the resulting wafer becomes a mold 20 ′ that provides the channel according to the channel design 12 ′.
[0010] FIG. 2 are perspective views of the steps of manufacturing a microfluidic chip according to the related art. As shown in FIG. 2 , PDMS in liquid form 30 is poured onto the mold 20 ′. Liquid PDMS 30 may be mixed with crosslinking agent. The mold 20 ′ with liquid PDMS 30 is then placed into a furnace to harden PDMS 30 . As PDMS is hardened, the hardened PDMS block 30 ′ duplicates the micro-channel 12 ″ according to the channel design. The PDMS block 30 ′ then may be separated from the mold 20 ′. To allow injection of fluid into the micro-channel 12 ″ (which will subsequently be sealed), inlet or outlet is then made in the PDMS block 30 ′ by drilling into the PDMS block 30 ′ using a needle. Then, the face of the PDMS block 30 ′ with micro-channels and a glass slide 32 are treated with plasma. Due to the plasma treatment, the PDMS block 30 ′ and the glass slide 32 can bond with one another and close the chip.
[0011] The microfluidic chip according to the related all has a micro-channel in the PDMS block. PDMS belongs to a group of polymeric organosilicon compounds that are commonly referred to as silicone, and can be deposited onto the master mold in liquid form and subsequently hardened.
[0012] However, PDMS is inherently porous and due to its polymer structure, PDMS is highly permeable. Thus, diffusion of fluid sample through PDMS has been observed. Such diffusion of fluid sample does not impact a microfluidic system that pumps fluid samples in doses as significantly as a continuous flow microfluidic system. In particular, when a continuous flow microfluidic system monitors treating and manipulating of the flowing fluid in real-time analysis applications, diffusion or unaccounted loss of fluid sample can significantly impact the real-time analysis. Thus, there exists a need for reducing diffusion or loss of fluid sample in micro-channel of a microfluidic chip.
SUMMARY OF THE DISCLOSURE
[0013] Accordingly, embodiments of the present disclosure are directed to a method of manufacturing microfluidic chips for handling fluid samples on a microfluidic level and microfluidic chips that can substantially obviate one or more of the problems due to limitations and disadvantages of the related art.
[0014] An object of embodiments of the present disclosure is to provide a method of manufacturing microfluidic chips to reduce fluid diffusion in micro-channel, and microfluidic chips manufactured using the same.
[0015] An object of embodiments of the present disclosure is to provide a method, of manufacturing microfluidic chips with micro-channel coating, and microfluidic chips manufactured using the same.
[0016] Additional features and advantages of embodiments of the present disclosure will be set forth in the description which follows, and in part will be apparent from the description, or may be learned by practice of embodiments of the present disclosure. The objectives and other advantages of the embodiments of the present disclosure will be realized and attained by the structure particularly pointed out in the written description and claims hereof as well as the appended drawings.
[0017] To achieve these and other advantages and in accordance with the purpose of embodiments of the present disclosure, as embodied and broadly described, a microfluidic chip device according to an embodiment of the present disclosure includes a substrate having a first thickness, at least one microfluidic pathway in the substrate, a coating along the microfluidic pathway, and a glass layer having a second thickness on the substrate and above the microfluidic pathway, wherein the coating contains cyanoacrylates, and the first thickness is greater than the second thickness.
[0018] In accordance with another embodiment of the present disclosure, as embodied and broadly described, a microfluidic chip device includes a substrate having a first thickness, at least one microfluidic pathway in the substrate, a coating along the microfluidic pathway, and a glass layer having a second thickness on the substrate and above the microfluidic pathway, wherein the coating contains an optically transparent material, and the first thickness is greater than the second thickness.
[0019] In accordance with another embodiment of the present disclosure, as embodied and broadly described, a method for manufacturing a microfluidic chip device includes etching a substrate having a first thickness for forming at least one microfluidic pathway in the substrate, coating the substrate, and bonding a glass layer having a second thickness on the substrate and above the microfluidic pathway, wherein the step of coating includes coating an optically transparent material, and the first thickness is greater than the second thickness.
[0020] In accordance with another embodiment of the present disclosure, as embodied and broadly described, a microfluidic chip device includes a coating along the microfluidic pathway, wherein the coating includes cyanoacrylates, an UV curable epoxy adhesive, a gel epoxy or epoxy under trade name of EPO-TEK OG175, MasterBond EP30LV-1 or Locite 0151.
[0021] In accordance with another embodiment of the present disclosure, as embodied and broadly described, a method for manufacturing a microfluidic chip device includes etching a substrate having a first thickness for forming at least one microfluidic pathway in the substrate and coating along the microfluidic pathway, wherein the coating includes coating with cyanoacrylates, an UV curable epoxy adhesive, a gel epoxy or epoxy under trade name of EPO-TEK OG1.75, MasterBond EP30LV-1 or Locite 0151.
[0022] It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are intended to provide further explanation of embodiments of the present disclosure as claimed.
BRIEF DESCRIPTION OF THE DRAWINGS
[0023] The accompanying drawings, which are included to provide a further understanding of embodiments of the present disclosure and are incorporated in and constitute a part of this specification, illustrate embodiments of the present disclosure and together with the description serve to explain the principles of embodiments of the present disclosure.
[0024] FIGS. 1A-1D are perspective views of manufacturing a microfluidic chip mold according to the related art.
[0025] FIG. 2 illustrates the steps of manufacturing a microfluidic chip according to the related art.
[0026] FIG. 3 is a perspective view of a microfluidic chip for a microfluidic system according to an embodiment of the present disclosure.
[0027] FIG. 4 is a side view of the microfluidic chip shown in FIG. 3 .
[0028] FIG. 5 is a side view of the microfluidic chip according to another embodiment of the present disclosure.
[0029] FIG. 6 is a top view of a heater for a microfluidic chip of a microfluidic system according to an embodiment of the present disclosure.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0030] Reference will now be made in detail to the preferred embodiments of the present disclosure, examples of which are illustrated in the accompanying drawings.
[0031] FIG. 3 is a perspective view of a microfluidic chip for a microfluidic system according to an embodiment of the present disclosure, and FIG. 4 is a side view of the microfluidic chip shown in FIG. 3 . As shown in FIGS. 3 and 4 , a microfluidic chip 100 includes a PDMS substrate 110 and a glass layer 120 on the substrate 110 . The glass layer 120 may be formed of borosilicate. As shown in the substrate 110 . For instance, the glass layer 120 may have a thickness of about 0.01 inch or less.
[0032] The substrate 110 includes micro-channels 130 . The micro-channels 130 form a microfluidic pathway, and the channels allow fluid samples to be flowed through therein. The micro-channels 130 may be formed by etching the substrate 110 .
[0033] After the micro-channels 130 are formed in the substrate 110 but prior to sealing micro-channels 130 with the glass layer 120 , the substrate 110 is coated with cyanoacrylates 112 to seal the surface pores of the substrate 110 . Cyanoacrylates are acylic resin and are mainly used as adhesives. However, cyanoacrylates are not used as adhesives in the micro-channels of the substrate 110 . Instead, cyanoacrylates are allowed to set to form a coating along the micro-channels 130 .
[0034] When coating the substrate 110 , the amount of cyanoacrylates deposited is controlled so as not to fill the micro-channels 130 of the substrate 110 . In addition or alternatively, the micro-channels 130 are formed wider and/or deeper in the substrate 110 to account for the subsequent coating thickness of cyanoacrylates 112 .
[0035] The microfluidic chip 100 further includes heaters 140 a , 140 b and 140 c . For example, the heaters 140 a , 140 b and 140 c may be resistive heating devices, such as thin-film heaters. The heaters 140 a , 140 b and 140 c may be formed by applying a thin film of conductive material directly on the glass layer 120 . For example, the heaters 140 a , 140 b and 140 c may include aluminum. More specifically, the heaters 140 a , 140 b and 140 c may have a thickness of about 0.001 inch or less.
[0036] The microfluidic chip 100 further includes temperature sensors 150 a , 150 b and 150 c . For example, the temperature sensors 150 a , 150 b and 150 c may be resistance temperature detectors. The temperature sensors 150 a , 150 b and 150 c provide real-time temperature detection to more than one zones or portions of the microfluidic chip 100 . The real-time temperature detection is then used to control heaters 140 a , 140 b and 140 c , respectively. As such, the microfluidic chip 100 may have independently-temperature-controlled zones.
[0037] A microprocessor (not shown) may be connected to the temperature sensors 150 a , 150 b and 150 c and the heaters 140 a , 140 b and 140 c to provide independently-temperature-controlled zones for the microfluidic chip 100 . For example, the microprocessor may implement a control algorithm, such as PID control to receive temperature inputs from the temperature sensors 150 a , 150 b and 150 c and dynamically controls the output of the heaters 140 a , 140 b and 140 c.
[0038] For real-time analysis, an optical sensor 160 is further included and can be placed above or below the microfluidic chip 100 . The optical sensor 160 provides real-time monitoring of the manipulation of the fluid sample in the micro-channel 130 of the microfluidic chip 100 . The same microprocessor (not shown) can also receive and control the optical sensor 160 .
[0039] FIG. 5 is a side view of the microfluidic chip according to another embodiment of the present disclosure. In FIG. 5 , a microfluidic chip 100 ′ includes a layer of cured optically transparent material 112 ′ between a substrate 110 ′ and a seal layer 120 ′. As shown in FIG. 3 , the thickness of the seal layer 120 ′ is much smaller than the thickness of the substrate 110 ′. For instance, the seal layer 120 ′ may have a thickness of about 0.01 inch or, less.
[0040] The substrate 110 ′ includes micro-channels 130 ′. The micro-channels 130 ′ form a microfluidic pathway, and the channels allow fluid samples to be flowed through therein. The micro-channels 130 ′ may be formed by etching the substrate 110 ′.
[0041] After the micro-channels 130 ′ are formed in the substrate 110 ′ but prior to sealing micro-channels 130 ′ with the seal layer 120 ′, the substrate 110 ′ is coated with an optically transparent material to seal the surface of the substrate 110 ′. The optically transparent material is allowed to set or hardened to form the layer of cured optically transparent material 112 ′. An UV curable epoxy adhesive, a gel epoxy or epoxy under trade name of EPO-TEK OG175, MasterBond EP30LV-1 or Locite 0151 may be used to coat the surface of the substrate 110 ′.
[0042] When coating the substrate 110 ′, the amount of the optically transparent material deposited are controlled so as not to fill the micro-channels 130 ′ of the substrate 110 ′. In addition or alternatively, the micro-channels 130 ′ are formed wider and/or deeper in the substrate 110 ′ to account for the subsequent layer of cured optically transparent material 112 ′.
[0043] The microfluidic chip 100 ′ further includes heaters 140 a ′, 140 b ′ and 140 c ′. For example, the heaters 140 a ′, 140 b ′ and 140 c ′ may be resistive heating devices, such as thin-film heaters. The heaters 140 a ′, 140 b ′ and 140 c ′ may be formed by applying a thin film of conductive material directly on the seal layer 120 ′. For example, the heaters 140 a ′, 140 b ′ and 140 c ′ may include aluminum. More specifically, the heaters 140 a ′, 140 b ′ and 140 c ′ may have a thickness of about 0.001 inch or less.
[0044] The microfluidic chip 100 ′ further includes temperature sensors 150 a ′, and 150 c ′. For example, the temperature sensors 150 a ′, 150 b ′ and 150 c ′ may be resistance temperature detectors. The temperature sensors 150 a ′, 150 b ′ and provide real-time temperature detection to more than one zones or portions of the microfluidic chip 100 ′. The real-time temperature detection is then used to control heaters 140 a ′, 140 b ′ and 140 c ′, respectively. As such, the microfluidic chip 100 may have independently-temperature-controlled zones.
[0045] A microprocessor (not shown) may be connected to the temperature sensors 150 a ′, 150 b ′ and 150 c ′ and the heaters 140 a ′, 140 b ′ and 140 c ′ to provide independently-temperature-controlled zones for the microfluidic chip 100 ′. For example, the microprocessor may implement a control algorithm, such as PID control to receive temperature inputs from the temperature sensors 150 a ′, 150 b ′ and 150 c ′ and dynamically controls the output of the heaters 140 a ′, 140 b ′ and 140 c′.
[0046] Although not shown, for real-time analysis, an optical sensor is further included and can be placed above or below the microfluidic chip 100 ′. The optical sensor provides real-time monitoring of the manipulation of the fluid sample in the micro-channel 130 ′ of the microfluidic chip 100 ′. The optical sensor may be controlled by a microprocessor.
[0047] FIG. 6 is a top view of a heater for a microfluidic chip of a continuous-flow microfluidic system according to an embodiment of the present disclosure. As shown in FIG. 6 , a thin-film heater 140 for a microfluidic chip of a microfluidic system preferably may include two electrical interface pads 142 a and 142 b . The two electrical interface pads 142 a and 142 b may receive voltage and/or current. More specifically, electrical resistance or heat may be generated by the thin-film heater 140 based on V 2 /R or I 2 ×R. Such heat may provide temperature to the channels 130 or 130 ′ shown in FIG. 4 or 5 .
[0048] Preferably, the thin-film heater 140 is spread above the channels 130 or 130 ′ evenly to provide consistent heating of the channel below. The thin-film heater 140 may have a line-like shape between the two electrical interface pads 142 a and 142 b . For example, the thin-film heater 140 may have elongated strips that are substantially parallel with one another.
[0049] It will be apparent to those skilled in the art that various modifications and variations can be made in the microfluidic chip of embodiments of the present disclosure without departing from the spirit or scope of the present disclosure. Thus, it is intended that embodiments of the present disclosure cover the modifications and variations of this disclosure provided they come within the scope of the appended claims and their equivalents. | A microfluidic chip is disclosed herein. In an embodiment, the microfluidic chip includes a body including at least one microfluidic pathway configured to receive a fluid sample, the at least one microfluidic pathway including a coating configured to reduce fluid diffusion and seal a surface of the at least one microfluidic pathway, and a heating device located on the body and forming a heating zone within a portion of the at least one microfluidic pathway. | 1 |
BACKGROUND OF THE INVENTION
Hypercholesterolemia is known to be one of the prime etiological components of cardiovascular disease such as atherosclerosis, and there is still no effective antihypercholesterolemic agent available that has found wide patient acceptance. The bile acid sequestrants seem to be moderately effective but they must be consumed in large quantities, i.e. several grams at a time and they are not very palatable.
There are agents known, however, that are very active antihypercholesterolemic agents that function by limiting cholesterol biosynthesis by inhibiting the enzyme, HMG-CoA reductase. These agents include the natural fermentation products compactin and mevinolin and a variety of semi-synthetic and totally synthetic analogs thereof. These compounds have the following general structural formula: ##STR2## wherein R is ##STR3##
One group of totally synthetic analogs are disclosed in U.S. Pat. No. 4,375,475 and have the same general structural formula: ##STR4## wherein R is ##STR5## In the usual course of synthesis of these lactones an intermediate ester and dihydroxy acid are encountered: ##STR6## Each of these entities, as well as the lactone, demonstrate antihypercholesterolemic activity in vivo, of comparable magnitude. However, for these compounds to manifest a useful degree of activity, it.Iaddend. ve.ionship shown in the structures.[...].r .[.3R:5S/3S:5R.].
One of the prior art synthesis of these compounds comprises reduction of β-hydroxyketones 2a or 2b ##STR7## A stereoselective process for the reduction of β-hydroxyketones 2a.Iaddend.been described and disclosed in a copending U.S. patent application Ser. No. 725,891, filed Apr. 25, 1985.
SUMMARY OF THE INVENTION
This invention relates to a novel two step process for the preparation of the intermediate ester 2a in the synthesis of antihypercholesterolemic agents which contain a 4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one moiety. The process involves the enantiomeric aldol condensation of an appropriately substituted aldehyde with the enolate of.Iaddend.with an alkyl acetate. resultant .[.enolate.].
DETAILED DESCRIPTION OF THE INVENTION
A process for the preparation of a compound represented by the following general formula (I): ##STR8## wherein R is: ##STR9## wherein Q is ##STR10## R 5 is H or OH; R 6 is hydrogen or methyl; and a,b,c, and d represent optional double bonds, especially where b and d represent double bonds or a,b,c and d are all single bonds; or ##STR11## wherein E is --CH═CH-- or --CH 2 CH 2 --; and
R 1 , R 2 and R 3 are each selected from halo such as chloro, bromo or fluoro,
C 1-4 alkyl,
C 1-4 haloalkyl,
phenyl
phenyl with one or more substituents independently selected from halo C 1-4 alkyl, and C 1-4 alkoxy, or
R 4 O in which R 4 is phenyl, halophenyl, or
substituted phenyl-C 1-3 alkyl wherein the substituents are selected from halo and C 1-4 haloalkyl;
comprises:
(1) reacting a compound of the formula (II)
RCHO (II)
wherein R is defined above, with the enolate of.Iaddend.of the formula (III) riphenylethanol ##STR12## wherein M + is a cation derived from sodium, potassium, lithium, magnesium or zinc, to afford a compound of the formula (IV) ##STR13## wherein R and M + defined above; and
(2) reacting the compound of the formula (IV) with the enolate of a C 1-5 alkylacetate, followed by mild acid hydrolysis to obtain the compounds of the formula (I).
In a first preferred embodiment R is the radical (A). Illustrative of this embodiment are the compounds of the formula I wherein R 5 is H, R 6 is H or CH 3 and b and d represent double bonds or a, b, c and d are all single bonds.
In a second preferred embodiment, R is the radical (B). Illustrative of this embodiment are the compounds of the formula I wherein E is --CH═CH--, R 1 is in the 6-position and represents phenyl with 1 or 2 substituents independently selected from chloro, fluoro, methyl and methoxy; and R 2 and R 3 are independently selected from halo and C 1-3 alkyl in the 2- and 4-positions.
In the most preferred embodiment, R is: ##STR14##
The preparation of the compound of formula (IV) is accomplished by an aldol condensation of the appropriately substituted aldehyde with the enolate of.Iaddend.under standard aldol conditions as described in Braun et al., Tetrahedron Letters, Vol. 25, No. 44, pp 5031-5034 (1984). Specifically.Iaddend.is formed under anhydrous conditions in an aprotic solvent utilizing a non-nucleophilic base. Then the appropriately substituted aldehyde is added at low temperatures, between -100° C. and -30° C., preferrably -78° C. and the reaction allowed to go to completion.
The preparation of the compound of the formula (I) is accomplished by a condensation of the compound of the formula (IV), with or without isolation, and with an enolate of a C 1-5 alkyl acetate. When the compound of (IV) is isolated from the reaction mixture of the previous step, it is treated with between 2.0 and 3.0 equivalents, preferrably 2.5 equivalents, of a non-nucleophilic base, in an aprotic solvent, followed by the addition of the enolate of C 1-5 alkyl acetate which is formed in an aprotic solvent with a non-nucleophilic base. When the compound of (IV) is not isolated the enolate of C 1-5 alkyl acetate is added directly to the reaction mixture of the previous step. This condensation is conducted at a temperature between 0° C. and -50° C., preferably -10° for a period of 30 minutes to 16 hours.
Illustrative of the non-nucleophilic bases which may be employed in both steps of this process are alkali metal amides of the formula:
M.sup.+ N.sup.- R.sup.7 R.sup.8 .8.].
wherein M + is a cation derived from sodium, potassium, lithium, magnesium or zinc and R 7 and R 8 independently are C 1-3 alkyl or when taken together with the nitrogen atom to which they are attached form a .Badd.5 or 6-membered heterocyclic ring and alkyl metals such as butyllithium. The preferred non-nucleophilic base is lithium diisopropylamide. Examples of the aprotic solvents that may be employed in both steps of this process are ethers, such as diethyl ether, tetrahydrofuran, 1,2-dimethoxyethane and the like. The preferred solvent is tetrahydrofuran.
The reactions may conveniently be worked up by quenching with saturated ammonium chloride solution, and extracting into an organic solvent.
The starting materials wherein R is the radical (A) may be prepared by using the synthetic methods described by HSU et al., J. Am. Chem. Soc., 1983, 105, pp. 593-601. The starting materials wherein R is the radical (B) are known in the art.
The following examples illustrate the present invention and as such are not to be considered as limiting the invention set forth in the claims appended hereto.
EXAMPLE 1
Preparation of .[.(R)-2-[(E)-4-[4'-fluoro-3,3',5-trimethyl[1,'1-bipehnyl]-2-yl]-3-hydroxy .Iadd.(S)-2-hydroxy-1,2,2-triphenylethyl (E)-5-(4'fluoro-3,3',5-trimethyl[1,1'-biphenyl]-2-yl)-3-hydroxy-4-pentenoa.Iaddend.
.[.To a suspension of (R)-2-acetoxy-1,2,2-triphenylethanol (332 mg, 1 .Iadd.To a suspension of (S)-2-acetyloxy-1,1,2-triphenylethanol (332 mg, 1 mmol), prepared according to the general procedure of Braun but.Iaddend.in tetrahydrofuran (2 ml) at -78° C. under nitrogen was added lithium diisopropylamide (prepared from 2.2 mmol of butyllithium and 2.42 mmol of diisopropylamine) in tetrahydrofuran (1 ml) and the reaction allowed to warm to 0° C. To the reaction mixture which was recooled to -78° C. was added E-3-(4'-fluoro-3,3',5-trimethyl[1,1'-biphenyl]-2-yl)-propenal in. After 30 minutes at -78° C. the reaction was quenched with a saturated solution of ammonium chloride. The desired product was extracted into ethyl acetate, dried over magnesium sulfate, and flash chromatographed over silica gel with hexane:ethylacetate(4:1) to give a yellow wax.
EXAMPLE 2
Preparation of tert-butyl (E)-7-(4'-fluoro-3,3',5-trimethyl-[1,1-biphenyl]-2-yl)-3-oxo-5-hydroxy-6-heptenoate
Lithium diisopropylamide (6.65 mmol) was prepared by the addition of 4.75 ml of 1.4M n-butyllithium in hexanes to a solution of diisopropylamine (665 mg, 6.65 mmol) in 10 ml of tetrahydrofuran at -25° C. to -35° C. The mixture was stirred for 30 minutes at -25° C. and cooled to -78° C. t-Butylacetate (771 mg, 6.65 mmol) was added dropwise and the solution was stirred for 30 minutes at -78° C. and then warmed to -25° C. over 1 hour. A solution of .[.(R)-2-[(E)-4-(4'-fluoro-3,3',5-trimethyl]1,1'-biphenyl]-2-yl]-3-hydroxy .Iadd.(S)-2-hydroxy-1,2,2-triphenylethyl(E)-5-(4'-fluoro-3,3',5-trimethyl-[.Iaddend.(800 mg, 1.33 mmol) in 2 ml tetrahydrofuran was added and the mixture was stirred for 1 hour at -25° C. and warmed to 22°-24° C. and stirred for 16 hours. The reaction mixture was quenched with a saturated solution of ammonium chloride and the product was extracted into methylene choride, dried over sodium sulfate and concentrated in vacuo to give the titled product.
EXAMPLE 3
.Iaddend.-biphenyl]-2-yl)-3-oxo-5-hydroxy-6-heptenoate (one-pot)
.Iaddend.(166 mg, 0.5 mmol) in tetrahydrofuran (1 ml) at -78° C. under nitrogen was added lithium diisopropylamide (prepared from 1.2 mmol butyllithium and 1.2 mmol of diisopropylamine) in tetrahydrofuran (0.5 ml) and the reaction was allowed to warm to 0° C. To the reaction mixture which was recooled to -78° C. was added.Iaddend.-biphenyl]-2-yl)-propenal (132 mg, 0.5 mmol) in tetrahydrofuran (0.5 ml). After 30 minutes at -78° C., to the reaction mixture lithium tert butylacetate (prepared from tert butyl acetate 3.0 mmol, butyllithium 3.0 mmol and diisopropylamine 3.0 mmol) in tetrahydrofuran (3.0 ml) was added and the reaction mixture allowed to warm to -20° C. over 30 minutes. The mixture was then warmed to 22° and stirred.Iaddend.16 hours. The reaction was quenched with a saturated solution of ammonium chloride and the product extracted into methylene chloride. The organic phase was washed with saturated sodium chloride, dried over sodium sulfate and concentrated in vacuo to afford the above tilted product.
EXAMPLES 4 TO 13
Utilizing the general procedures of Examples 1 and 2 or 3, the following compounds of the Formula I are prepared from the appropriate starting materials.
______________________________________CompoundNumber .[.R.sup.1.].tep .Iadd.R.Iaddend.______________________________________ ##STR15##5 ##STR16##6 ##STR17##7 ##STR18##8 ##STR19##9 ##STR20##10 ##STR21##11 ##STR22##12 ##STR23##13 ##STR24##______________________________________ | .Iaddend.hypercholesterolemic compounds of the HMG-CoA reductase type of the following general formula (1): ##STR1## involving an enantioselective aldol condensation is disclosed. | 2 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a method of constituting a robot consisting of a plurality of robot cells that can operate independently, are connected to one another and move coordinately due to information exchange between them to perform a manipulative action. The present invention relates also to an apparatus for realizing such a robot.
2. Description of the Prior Art
In a conventional robot, the function of the robot is distributed to each portion of the robot, the data from each distributed portion is gathered by a central processing unit, and the central processing unit in turn operates each distributed portion by giving an instruction thereto.
Therefore, it has been necessary to produce a specific apparatus for each distributed portion, and when the central unit is out of order or operates abnormally, it is likely that the robot as a whole undergoes a breakdown or operates dangerously. Moreover, the robot must be changed in accordance with the size of an object which is to be dealt with by the robot. The freedom of operation of the robot, which is determined by the number of a joints of arm, is low, so that the robot can not operate flexibly and continuously, and its response is low.
SUMMARY OF THE INVENTION
The present invention is directed to provision of a robot apparatus which can be assembled by merely combining in various ways a plurality of autonomous robots cells, that can operate independently with one another, so as to eliminate the necessity of a central unit, but has the advantage that it does not undergo system breakdown when one or more of the robot cells is or are out of order, and has a high response because the individual robot cells react simultaneously, can perform flexible operations, and because they exchange information between them and coordinate with one another to control their operations by themselves.
Each robot cells includes first means for detecting its own operating condition, second means for detecting the operation of the other robot cells, means for setting the object of its own operation on the basis of the conditions detected by the first and second means, and means for controlling its own operation in accordance with the object of the overall operation.
The cellular type robot apparatus of the invention consists of at least one group of robot cells of the type described above that are connected with one another, and may include third means for setting the object of the overall operation of the group of robot cells.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1 and 2 show the overall construction of the system of the present invention;
FIG. 3 shows an arm driving device of one embodiment of the present invention;
FIG. 4 shows a first embodiment of the cell of the present invention;
FIG. 5 shows one embodiment of a controller inside the cell of the present invention;
FIGS. 6 through 8 show the concepts of the operation of a group of robot cells of the present invention;
FIG. 9 shows the construction of controller inside the cell of the present invention;
FIG. 10 shows the concept of the motion of the arm of the cellular robot of one embodiment of the present invention; and
FIGS. 11 through 13 show the operation due to the relation between a group of cells of the present invention and an object.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1 shows the overall construction of the system. The robot is constructed as a whole by a plurality of robot cells 11, 12, . . . , and these cells are connected to adjacent robot cells by arms 111, 121, . . . 112, 212, . . . , . In FIG. 1, the robot cells are shown disposed on a two-dimensional plane, and each cells 11, 12, . . . is connected to the adjacent robot cells on the lateral and longitudinal axes by the lateral arms 111, 121, . . . and the longitudinal arms 112, 122, . . . , respectively.
The structure of each robot is changed as depicted in FIG. 2 when the lengths of the respective lateral and longitudinal arms are adjusted. An arm driver such as shown in FIG. 3 and a controller for driving the arm such as shown in FIG. 5 are incorporated in each robot cell. Each controller is connected to the controllers of the adjacent robots by a transmission medium so as to exchange information. Since the information is exchanged between the adjacent robot cells, each cell operates cooperatively.
FIG. 3 shows the arm driver of each robot cell. One of the arms is an active arm 2211 equipped with a servo motor 2215 and a gear 2213, while the other is a negative arm 2212 equipped with a guide 2214 for the gear 2213. These active and negative arms 2211 and 2212 are connected to the robot cell main body by shafts 2216 and 2217, respectively. Unless these shafts are locked, the arms can freely change their directions. The arm length can also be adjusted freely by rotating the gear 2213 using the servo motor 2215.
As shown in FIG. 4, the active arms 2211, 2221 and the negative arms 1222 and 2112 are disposed inside the robot cell in the lateral and transverse directions, respectively, and are connected to the four robot cells adjacent thereto. The robot cell can move freely in the lateral and longitudinal directions by the active arms 2211 and 2221. In the active arms, too, the gear can be freely rotated (or be brought into the free state) by cutting off the power of the servo motor 2215. The arm length can be fixed (or locked) by fixing the gear 2213. A longitudinal arm fixing connector 1232 is disposed so as to integrally connect the active/negative arms 1222, 2221 of the longitudinal axis and to prevent them from rotating independently.
The internal construction of the robot cell is such as shown in FIG. 5. The controller 22011 calculates the moving quantity of the arm on the basis of information applied thereto from sensors 22014, 22024 for recognizing an object existing in the longitudinal and lateral directions, for example, from an angle sensor for measuring the angle between the negative longitudinal and lateral arms, and from the adjacent robot cells through the transmission routes 1222, 2122, 2223, 2232, and generates an instruction to servo controllers 22012, 22022 so as to actuate the servo motors 2215, 2225 on the active arms in both lateral and longitudinal directions. The servo motors 2215, 2225 rotate on the basis of this instruction and turn the gear 2213. The angle of rotation of the servo motors 2215, 2225 are sensed by the sensors 22013, 22023, and are fed back to the controller 22011. If the instructed angle of rotation is different from the actual angle of rotation of the servo motor, the controller applies a correcting angle of rotation to the servo controller.
The controller also gives the instruction as to whether the gear should be kept under the free or locked state.
FIG. 9 shows the internal construction of the controller. The processor 22010 of the controller exchanges the data with the adjacent robot cells through the transmission routes 1222, 2122, 2232, 2223 and interfaces 220111, 220112. It also gives and receives signal data with the sensor, the servo sensor and the servo motor through the interfaces 220117-2201111. The data received from, or to be delivered to, the interfaces 220111, 220113, 220115, 220117, 220119, 2201111 are stored in buffers 1, 220113. On the other hand, the data to be received from and delivered to, through the interfaces 220114, 220116, 220118, 2201110, 2201112 are stored in buffers 2, 220114. The buffer 1 stores the data relating to the lateral direction, and the buffer 2 does the data on the longitudinal direction. On the basis of the data inside these buffers, the processor 220110 calculates the adjusting quantities of the lateral and longitudinal active arms, and the result of calculation is stored in each arm file 220115, 220116. The processor 220110 controls the servo motors 2215, 2225 on the basis of the data inside these files 220115, 220116.
The operation of each robot cell and the operation of robot part formed of a group of robot cells will now be described with reference to FIGS. 6 through 8.
It will be assumed that the robot cells 11 through 37 are arranged in three columns and seven rows and 17, 27 and 37 are fixed to support poles. These robot cells are directed (1) to encompass an object 1, (2) to grip the object 1 with a predetermined force, and (3) to move the object 1, and the cell operate in the three steps in accordance with the stated objective of moving object. First of all, the first step will be described. Assuming now that the object 1 and the robot part formed of the group of robot cells are spaced apart from each other as shown in FIG. 6, then each robot cell extends the lateral arm if the robot cell is out of contact the object 1. In this case, the longitudinal arm is locked and the lateral arms of the cells 21-27, 31-37 are kept free so that the cells of each row move in parallel with one another. When the lateral arms of the robot cells 11-17 are gradually extended, the sensor 22024 of the cell 11 first senses the object 1. Then, the free state of the lateral arm of each robot cell 11, 21, 31 is released. As the arms of the robot cells 11-17 are extended further, robot cell 11 moves towards the object 1, so that the arm between the robot cells 11 and 12 keeps an angle θ relative to the longitudinal arms between the robot cells 32, 22 and 12. The robot cells 11, 21, 31 control the active arms so that the lateral arms of the adjacent robot cell pairs (11, 12), (21, 22), (31, 32) of each row are parallel to one another. Therefore, the robot cell 12 which detects the change of the longitudinal/lateral negative arm angle θ by its arm angle sensor 22015 informs those robot cells 11, 22 which have the active arms and are adjacent thereto in the lateral and longitudinal directions, of the angle θ at that time.
Upon receiving this data θ, the robot cell 22 likewise transmits the data to the adjacent cells 21 and 32, at a scheduled time and the robot cell 32 transmits it to the cell 31 upon receiving the data θ. In this manner, the angle θ is detected at a scheduled time and is transmitted to the adjacent robots. The robot cell 11 informs the robot cells 21 and 31 of the arm length between the cells 11 and 12. The robot cells 21, 31 having the active arms calculate the lateral arm lengths in accordance with the algorithm shown in FIG. 10. As the arm length h between the robot cells 11 and 21 is known in advance, the robot cell 21, for example, calculates the lateral arm length l (21, 22) in accordance with the following equation on the basis of the lateral arm length h and the angle φ informed from the robot cells 12 and 11:
l (21, 22)=l-2h cos θ (1)
Likewise, the robot cell 31 calculates l (31, 32) in accordance with the following equation:
l (31, 32)=l-4h cos θ (2)
The robot cells 21 and 31 move the servos of the lateral active arms in accordance with this value, thereby adjusting the arm lengths. When the cells 21 and 31 adjust the arm lengths, the cell 11 does not change the arm length, while the cell 12 fixes the shaft 2216 of the arm between it and the cell 11 to prevent its rotation.
In this manner, the robot cell 11 changes the arm angle on the basis of the operations of the object sensors 22014, 22024 while extending the lateral arm but not separating away from the object. If the arm angle between the robot cells 11 and 12 changes, each robot cell 21-27, 31-37 adjusts the arm in accordance with the algorithm described above.
In order to let the robot cells 12-17 smoothly entwine the object 1, the cells 12, 22, 32 on each row periodically send information on the arm angle and length relative to the robot cell 11, 21, 31 to the subsequent robot cell 13, 23, 33 on the rear row. Similarly, the cells 13, 23, 33 inform the subsequent cells 14, 24, 34 of the arm angle and length at that time. In this manner, the robot cells on the front row send information on the existing arm angle and length to the subsequent cells on the rear row. As each robot cell advances and reaches the position where the subsequent cell has been occupied, it adjusts the arm angle and length on the basis of the data that has already given thereto.
Incidentally, when the arm angle θ becomes small and the arm length between the adjacent robot cells 11-12 becomes small, the arm length l (31, 32) between the robot cells 31 and 32 is below the minimum arm length l min , that is, ##EQU1## and the robot cell 31 can not achieve the arm angle θ. In other words, since the robot 31 can not attain the arm angle θ, it comes into contact with the robot cell 32. Since such occurrence is possible, each robot cell controls the servo so as to realize the minimum arm length l min if the calculated value of the lateral arm length is below the predetermined minimum arm length l min .
Judgement whether or not the arms entwine the object is made in the following manner. If the arms are judged as entwining the object, the second step mentioned above is followed. FIG. 11 shows the state in which the arms encompass the object 1. The robot cells 12 through 19 between the robot cells 11 and 19 on both ends come into contact with the object 1, and the robot cell 20 calculates the angle of their lateral arms on the basis of the value of the arm angle sensor 22015. If the angle θ exists on the side opposite to the longitudinal arm,
θ>0
and when the angle exists on the side of the longitudinal arm,
θ<0.
In FIG. 11, therefore,
θ 5 <0
for the robot cell 16, and
θ 1 , θ 2 , θ 3 , θ 4 , θ 6 , θ 7 , θ 8 , θ 9 >0
for the robot cells other than the cell 16. Each robot cell exchanges this angle at a scheduled time, and calculates the sum θ of these angles: ##EQU2##
When θ is greater than a certain predetermined angle θ, the arms are judged as entwining the object 1.
Incidentally, in FIG. 7, it is assumed that among the tips of the group of robot cells, only one robot cell 11 senses the object 1. However, the robot cells 11, 21, 31 might sense simultaneously the object 1 as depicted in FIG. 12. In such a case, each robot cell of the group can not extend the arm. In the case of FIG. 7, too, there might be the case in which the robot cell 11 does not slide on the object 1 when it comes into contact with the object, and can not extend the arm, either. In this case, the robot cell 11 of the first row, for example, is arranged in advance so as to slide along the object. Therefore, the robot cell 21 contracts the longitudinal active arm by a predetermined length, and makes free the lateral active arm of the robot cell 11. As a result, the robot cell 11 is attracted to the robot 12 as shown in FIG. 13. Next, the arm angle between the robot cells 11 and 12 is fixed, and the robot cell 21 extends the longitudinal active arm to the original length. Thereafter, the robot cells 11-17 of the first row extend their lateral active arms and encompass the object 1.
The second step is to grip the object 1 with a predetermined level of force when the group of the robot cells encompass the object 1. First, each robot cell stops extending the lateral arm. The robot cells 21-27 and 31-37 other than those of the first row fix the arm angles in the longitudinal and lateral directions, respectively.
Next, the robot cells 21-26 make control so as to extend the ordinate arm length between the robot cells that are in contact with the object 11-16 and the robot cells 21-26. After the arms are extended in a predetermined length, control of fastening the object 1 is completed.
The third step is to move the object that has thus been gripped. This can be accomplished when the robot cells on the column other than the robot cells coming into contact with the object 1 change their arm length in the same way as in the first step.
Since the robot of the present invention consists of a large number of robot cells, the robot does not undergo breakdown even when part of the cells are out of order. It will be assumed that the robot cell 22 of the second row, for example, in FIG. 7 is out of order and enters the free state. In this case, the arm length of the robot cell 22 is primarily determined by the control of the arm length of the adjacent robot cells. When the robot cell 12 of the first row is out of order, the longitudinal/lateral arm angle θ can not be measured. Accordingly, the robot cells 11, 21 and 31 keep the previous arm lengths fixed. When the robot cell 32 of the third row is out of order, no change of the control method is necessary for the other robot cells. However, when any of the robot cells 11, 21, 31 of the first column is out of order, the fastening control of the second step can not be effected, so that the robot cells 12, 22, 32 of the second row make control in place of the former.
The embodiment described above deals with the method of controlling a robot member formed by a group of robot cells when the object 1 exists, but even when the object 1 does not exist, the group of robot cells can be operated in accordance with a predetermined pattern. This can be accomplished by informing each robot cell of the first row, of the lateral arm length and of the arm angle so that each robot cell can make necessary control.
As can be clearly understood from the description that has been thus given, the hardware and software for each robot cell are uniform, and control by each robot cell is made through the communication between the adjacent robot cells. Accordingly, there is no necessity at all of the change of the content of each robot cell even when the number of robot cells is increased or decreased.
Though the robot structure described above is a rectangular shape consisting of three rows, a robot construction consisting of four or more rows or a construction having a hexagonal shape can be similarly realized.
The arm control of each robot cell may be made by methods other than the method described above.
The present invention makes it possible to constitute a robot by merely combining a plurality of autonomous robot cells having the same function, and to change the number of robot cells to be combined in accordance with an intended object. The hardware and software of the other robot cells need not be changed at all even when the combination of the robot cells or particular robot cells are expanded or diminshed. Moreover, the robot as a whole does not undergo breakdown even when one or more of these robot cells are out of order, but can keep the predetermined function. Since a large number of robot cells can be used, the freedom of the operation of the robot as a whole can be increased in proportion to the number of interconnected robot cells employed. Since each robot cell operates independently, the response of the robot as a whole can be improved. | This invention relates to a cellular type robot apparatus consisting of a plurality of robot cells each having intelligence, wherein each robot cell controls its own operation on the basis of information exchange with adjacent robot cells. The operations of the robot cells are as a whole coordinated, and each robot cell can be controlled without the necessity of change of hard- and soft-wares even when one or more of the robot cells are out of order or when the robot needs to be expanded. Each robot cell can be provided so that the robot can be increased or decreased in a building block arrangement. More definitely, each robot cell has arms corresponding to hands and feet, and is able to control its own operation. As the robot cells are connected and combined through transmission routes so as to be able to exchange information, they can operate cooperatively as a group to perform a manpulative action. The operation of the group of robot cells is designed also to constitute the shape of a predetermined pattern besides the operations of entwining an object, and gripping and moving the object. | 1 |
FIELD OF THE INVENTION
The present invention relates to hydrolytically modified, biodegradable polymers and methods of hydrolytically modifying biodegradable polymer. More particularly, the present invention relates to a modified polylactide composition and a process of modifying polylactides. In a preferred embodiment, the invention relates to a method of grafting polar groups onto polylactides and grafted polylactide compositions produced by the method.
BACKGROUND OF THE INVENTION
Even though the amount of plastics, hereinafter polymers, used in a variety of consumer goods, packaging and medical articles has not significantly increased over the past twenty years, the common perception is that more and more non-degradable plastics are filling up our limited landfill space. Despite this perceived disadvantage, polymers continue to be used in the manufacture of consumer goods, packaging and medical articles because plastics offer many advantages over the more traditional materials: wood, glass, paper, and metal. The advantages of using polymers include decreased manufacturing time and costs, improved mechanical and chemical properties, and decreased weight and transportation costs. It is the improved chemical resistance properties of the majority of plastics that result in their non-degradability.
Disposal of waste materials, including food waste, packaging materials and medical waste, into a typical landfill provides a relatively stable environment in which none of these materials is seen to decompose at an appreciable rate. Alternative waste disposal options have been increasingly discussed and utilized to divert some fractions of waste from entombment. Examples of these alternatives include municipal solid waste composting, anaerobic digestion, enzymatic digestion, and waste water sewage treatment.
Much controversy is associated with the disposal of medical waste. Both government agencies and members of the private sector have been increasingly directing in-depth scrutiny and funds toward this subject. Admittedly, concerns over the fate of materials contaminated with infectious substances are valid and proper measures to insure the safety of health care workers and the general public should be taken.
Currently, medical waste can be categorized as either reusable and disposable. Categorization as to whether certain waste is reusable or disposable is customarily determined according to the material from which the article was constructed and the purpose for which the article was used.
After use, reusable medical articles are cleansed and sterilized under stringent conditions to ensure disinfection. In comparison, disposable medical articles are usually only used once. Even then, disposing procedures are not straightforward, rather they often involve several steps to safeguard against potential hazards. Typically, after use, disposable medical articles must be disinfected or sterilized, adding a significant cost prior to disposal into a specially designated landfill or waste incinerator. As a result, the disposal cost for the contaminated single use articles is quite high.
Despite the high cost of disposal, single use medical articles are desirable because of the assurance of clean, and uncontaminated equipment. Many times in the medical context, sterilization procedures conducted improperly can result in detrimental effects such as the transmission of infectious agents from one patient to another. Improper sterilization can also be disastrous in a laboratory setting, where, for example, contaminated equipment can ruin experiments resulting in tremendous costs of time and money.
Currently, disposable medical fabrics are generally composed of thermoplastic fibers such as polyethylene, polypropylene, polyesters, polyamides and acrylics. These fabrics can also include mixtures of thermoset fibers such as polyamides, polyarimides and cellulosics. They are typically 10-100 grams per square yard in weight and can be woven, knitted or otherwise formed by methods well known to those in the textile arts while the non-wovens can be thermobonded, hydroentangled, wet laid or needle punched and films can be formed by blow or cast extrusion or by solution casting. Once used, these fabrics are difficult and costly to dispose of and are non-degradable.
The use of polymers for various disposable articles is widespread and well known in the art. In fact, the heaviest use of polymers in the form of film and fibers occurs in the packaging and the disposable article industries. Films employed in the packaging industry include those used in food and non-food packaging, merchandise bags and trash bags. In the disposable article industry, the general uses of polymers occurs in the construction of diapers, personal hygiene articles, surgical drapes and hospital gowns, instrument pads, bandages, and protective covers for various articles.
In light of depleting landfill space and inadequate disposal sites, there is a need for polymers which are water-responsive. Currently, although polymers such as polyethylene, polypropylene, polyethylene terephthalate, nylon, polystyrene, polyvinyl chloride and polyvinyldene chloride are popular for their superior extrusion and film and fiber making properties, these polymers are not water-responsive. Furthermore, these polymers are generally non-compostable, which is undesirable from an environmental perspective.
Polymers and polymer blends have been developed which are generally considered to be water-responsive. These are polymers which purportedly have adequate properties to permit them to breakdown when exposed to conditions which lead to composting. Examples of such arguably water-responsive polymers include those made from starch biopolymers and polyvinyl alcohol.
Although materials made from these polymers have been employed in film and fiber containing articles, many problems have been encountered with their use. Often the polymers and articles made from these polymers are not completely water-responsive or compostable. Furthermore, some water-responsive polymers may also be unduly sensitive to water, either limiting the use of the polymer or requiring some type of surface treatment to the polymer, often rendering the polymer non water-responsive. Other polymers are undesirable because they have inadequate heat resistance for wide spread use.
Personal care products, such as diapers, sanitary napkins, adult incontinence garments, and the like are generally constructed from a number of different components and materials. Such articles usually have some component, usually the backing layer, constructed of a liquid repellent or water-barrier polymer material. The water-barrier material commonly used includes polymer materials such as polyethylene film or copolymers of ethylene and other polar and nonpolar monomers. The purpose of the water-barrier layer is to minimize or prevent absorbed liquid that may, during use, exude from the absorbent component and soil the user or adjacent clothing. The water-barrier layer also has the advantage of allowing greater utilization of the absorbent capacity of the product.
Although such products are relatively inexpensive, sanitary and easy to use, disposal of a soiled product is not without its problems. Typically, the soiled products are disposed in a solid waste receptacle. This adds to solid waste disposal accumulation and costs and presents health risks to persons who may come in contact with the soiled product. An ideal disposal alternative would be to use municipal sewage treatment and private residential septic systems by flushing the soiled product in a toilet. Products suited for disposal in sewage systems are termed "flushable". While flushing such articles would be convenient, prior art materials do not disintegrate in water. This tends to plug toilets and sewer pipes, frequently necessitating a visit from a plumber. At the municipal sewage treatment plant, the liquid repellent material may disrupt operations by plugging screens and causing sewage disposal problems. It therefore is necessary, although undesirable, to separate the barrier film material from the absorbent article prior to flushing.
In addition to the article itself, typically the packaging in which the disposable article is distributed is also made from a water-barrier, specifically water-resistant, material.
Water-resistivity is necessary to prevent the degradation of the packaging from environmental conditions and to protect the disposable articles therein. Although this packaging may be safely stored with other refuse for commercial disposal, and especially in the case of individual packaging of the products, it would be more convenient to dispose of the packaging in the toilet with the discarded, disposable article. However, where such packaging is composed of a water-resistant material, the aforementioned problems persist.
The use of lactic acid and lactide to manufacture a water-stable polymer is well known in the medical industry. Such polymers have been used in the past for making water-stable sutures, clamps, bone plates and biologically active controlled release devices. Processes developed for the manufacture of such polymers to be utilized in the medical industry have incorporated techniques which respond to the need for high purity and biocompatability in the final product. These processes, however, are typically designed to produce small volumes of high dollar-value products, with less emphasis on manufacturing cost and yield.
It is generally known that lactide polymers or poly(lactides) are unstable. However, the consequence of this instability has several aspects. One aspect is the biodegradation or other forms of degradation which occur when lactide polymers, or articles manufactured from lactide polymers, are discarded or composted after completing their useful life. Another aspect of such instability is the degradation of lactide polymers during processing at elevated temperatures as, for example, during melt-processing by end-user purchasers of polymer resins.
In the medical area there is a predominant need for polymers which are highly stable and therefore desirable for use in medical devices. Such a demand has historically been prevalent in the high value, low volume medical specialty market, but is now also equally prevalent in the low value, high volume medical market.
As described in U.S. Pat. No. 5,472,518, compositions comprised of multilayer polymer films are known in the art. The utility of such structures lies in the manipulation of physical properties in order to increase the stability or lifetime during use of such structure. For example U.S. Pat. No. 4,826,493 describes the use of a thin layer of hydroxybutyrate polymer as a component of a multilayer structure as a barrier film for diaper components and ostomy bags.
Another example of use of multilayer films is found in U.S. Pat. No. 4,620,999 which describes the use of a water soluble film coated with, or laminated to, a water insoluble film as a disposable bag. The patent describes a package for body waste which is stable to human waste during use, but which can be made to degrade in the toilet, at a rate suitable for entry into a sewage system without blockage, by adding a caustic substance to achieve a pH level of at least 12. Such structures are usually consist of a polyvinyl alcohol film layer coated with polyhydroxybutryate.
A similar excretion-treating bag allowing discarding in flush toilet or sludge vessel is disclosed in JP 61-42127. It is composed of an inner layer of water-resistant water-dispersible resin such as polylactide and an outer layer of polyvinyl alcohol. As disclosed in this patent, there are many examples of multilayer films that are utilized in disposable objects. Most of these examples consist of films or fibers which are comprised of external layers of an environmentally degradable polymer and an internal layer of water-responsive polymer. Typically, the external layers are comprised of polycaprolactone or ethylene vinyl acetate and the internal layer is comprised of polyvinyl alcohol. These examples, however, are all limited to compositions consisting of multilayers of different polymers, and do not encompass actual blends of different polymers.
A family of patents, EP 241178, JP 62-223112 and U.S. Pat. No. 4,933,182, describes a controlled release composition for treating periodontal disease. The controlled release compositions are comprised of a therapeutically effective agent in a carrier consisting of particles of a polymer of limited water solubility dispersed in a water soluble polymer. Although, the carrier of these inventions includes the use of more than one polymer, the disclosed carrier is not a blend because the water soluble polymer of limited solubility is incorporated in the water soluble polymer as particles ranging in average particle size from 1 to 500 microns.
The use of polymers for use in water-responsive articles is disclosed in U.S. Pat. No. 5,508,101, U.S. Pat. No. 5,567,510, and U.S. Pat. No. 5,472,518. This group of patents discloses a series of water-responsive compositions comprising a hydrolytically degradable polymer and a water soluble polymer. The compositions of this group, however, consist of articles constructed from polymers which are first formed into fibers or films and then combined. As such, the compositions are actually mini-layers of the individual polymer films or fibers. Therefore, although the fibers and films of the polymers of such compositions are considered to be in very close proximity with one another, they are not actual blends. The dispersion of one polymer within another in these compositions, is not viewed as approximately uniform since the individual polymers are essentially distinct and separate fibers or films.
U.S. Pat. No. 5,525,671 to Ebato et al. discloses a method of making a linear lactide copolymer from a lactide monomer and a hydroxyl group containing monomer. The polymer disclosed by Ebato is a linear lactide copolymer produced by reacting two monomers to form a linear polymer with a block or random structure. Ebato does not disclose graft copolymers.
Polymer blend compositions for making fibers and films that are optimally combined are desirable because they are highly stable. Optimal combination of polymers means that the polymers are connected as closely as possible without the requirement of co-polymerization. Although blended polymer compositions are known, improved polymer blends wherein the fibers and films are more intimately connected are desirable since the resulting composition is then more stable, pliable and versatile.
In addition to the need for polymer compositions that are highly stable, and therefore, suitable for regular use in most disposable articles, there is a simultaneous need for such polymer compositions to be water-responsive. What is needed therefore, is a material that may be utilized for the manufacture of disposable articles and which is water-responsive. Such material should be versatile and inexpensive to produce. The material should be stable enough for intended use but subject to degradation under predetermined conditions.
Moreover, there is an increased emphasis on environmentally safe materials and coatings. These coatings reduce the use of solvent-based coatings and rely, to an ever increasing degree, on polar coatings, such as water-based material. The utility of the graft copolymers of this invention includes, but would not be limited to, materials have a greater affinity for a polar coating.
Therefore, it is an object of this invention to make a hydrolytically modified, biodegradable polymer.
Another object of this invention is to make a thermally processable polymer.
Another object of this invention is to make a commercially viable polymer.
Another object of this invention is to make a thermally processable, biodegradable polymer which is more compatible with polar polymers and other polar substrates.
Another object of this invention is to make a hydrolytically modified, biodegradable polymer useful for making flushable, biodegradable articles.
Another object of this invention is to make a hydrolytically modified, biodegradable polymer useful for making blends with improved mechanical and physical properties.
Another object of this invention is to make a modified polylactide which has improved compatibility in blends with polar polymers.
Another object of the invention is to make improved blends comprising polylactides.
SUMMARY OF THE INVENTION
This invention discloses modified polylactide compositions comprised of polylactide grafted with polar monomers. This invention describes compositions of polylactide grafted with 2-hydroxyethyl methacrylate or poly(ethylene glycol) methacrylate and a reactive extrusion process for making modified polylactide compositions.
Polylactides are biodegradable polymers which are commercially viable and thermally processable. By grafting polar monomers onto a polylactide, the resulting modified polylactide is more compatible with polar polymers and other polar substrates. For flushable material development, the modified polylactide compositions of this invention have enhanced compatibility with water-soluble polymers such as polyvinyl alcohol and polyethylene oxide, than unmodified polylactide. The compatibility of modified polylactide compositions with a polar material can be controlled by the selection of the monomer and the level of grafting. Tailoring the compatibility of blends with modified polylactide compositions leads to better processability and improved physical properties of the resulting blend.
The water-responsive compositions disclosed in this invention have the unique advantage of being biodegradable so that the compositions and articles made from the compositions can be degraded in aeration tanks by aerobic degradation and anaerobic digestors by anaerobic degradation in waste water treatment plants. Therefore, articles made from the compositions of this invention will not significantly increase the volume of sludge accumulated at waste water treatment plants.
BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 is a plot of the viscosity versus the shear rate of a grafted polylactide in accordance with the present invention and an ungrafted polylactide, demonstrating the decrease in viscosity of grafted polylactide versus ungrafted polylactide.
DETAILED DESCRIPTION OF THE INVENTION
Polylactide (PLA) resins are produced by different synthetic methods, such as ring-opening polymerization of lactide or direct condensation polymerization from lactic acid. Both methods of polymerization are useful for this invention. PLA is a biodegradable polymer and has the chemical structure:
--CH(CH.sub.3)CO.sub.2 --!.sub.n.
The PLA compositions described in the following Examples were made by using a reagent grade PLA purchased from Aldrich Chemical Company of Milwaukee, Wis. (Aldrich Catalog number 42,232-6). The PLA purchased from Aldrich Chemical Company is biodegradable and has number-average molecular weight of approximately 60,000 and a weight-average molecular weight of approximately 144,000. This PLA is made up primarily of the L-isomer and has a glass transition temperature (T g ) of 60° C. Any PLA can be selected for use in this invention, and the molecular weights of the PLA may vary depending on the desired properties and use.
Ethylenically unsaturated monomers containing a polar functional group, such as hydroxyl, carboxyl, amino, carbonyl, halo, thiol, sulfonic, sulfonate, etc. are appropriate for this invention. Preferred ethylenically unsaturated monomers containing a polar functional group include 2-hydroxyethyl methacrylate (HEMA) and poly(ethylene glycol) methacrylate (PEG-MA). It is expected that a wide range of polar vinyl monomers would be capable of imparting the same effects as HEMA and PEG-MA to polylactide resins and would be effective monomers for grafting. The grafted PLA may contain from 1 to 20% of grafted polar monomers, oligomers, or polymers, Preferably, the grafted PLA contains 2.5 to 20% of grafted polar monomers, oligomers, or polymers, and most preferably 2.5 to 10% of grafted polar monomers, oligomers, or polymers.
Both the HEMA (Aldrich Catalog number 12,863-8) and the PEG-MA (Aldrich Catalog number 40,954-5) used in the Examples were supplied by Aldrich Chemical Company. The PEG-MA purchased from Aldrich Chemical Company was poly(ethylene glycol) ethyl ether methacrylate having a number average molecular weight of approximately 246 grams per mol.
The method for making the grafted polylactide compositions has been demonstrated by a reactive-extrusion process. The grafting reaction can also be performed in other reaction devices as long as the necessary mixing of PLA and HEMA and/or PEG-MA and any other reactive ingredients is achieved and enough energy is provided to effect the grafting reactions.
Other reactive ingredients which may be added to the compositions of this invention include initiators such as Lupersol 101, a liquid, organic peroxide available from Elf Atochem North America, Inc. of Philadelphia, Pa. Free radical initiators useful in the practice of this invention include acyl peroxides such as benzoyl peroxide; dialkyl; diaryl; or aralkyl peroxides such as di-t-butyl peroxide; dicumyl peroxide; cumyl butyl peroxide; 1,1 di-t-butyl peroxy-3,5,5-trimethylcyclohexane; 2,5-dimethyl-2,5-di(tbutylperoxy) hexane; 2,5-dimethyl-2,5-bis (t-butylperoxy) hexyne-3 and bis(a-t-butyl peroxyisopropylbenzene); peroxyesters such as t-butyl peroxypivalate; t-butyl peroctoate; t-butyl perbenzoate; 2,5-dimethylhexyl-2,5-di(perbenzoate) t-butyl di(perphthalate); dialkyl peroxymonocarbonates and peroxydicarbonates; hydroperoxides such as t-butyl hydroperoxide, p-methane hydroperoxide, pinane hydroperoxide and cumene hydroperoxide and ketone peroxides such cyclohexanone peroxide and methyl ethyl ketone peroxide. Azo compounds such as azobisisobutyronitrile may also be used.
Furthermore, other components known in the art may be added to the graft polymers of this invention to further enhance the properties of the final material. For example, polyethylene glycol may be further added to improve melt viscosity. Additives of other types may also be incorporated to provide specific properties as desired. For example, anti-static agents, pigments, colorants and the like may be incorporated in to the polymer composition. Additionally, processing characteristics may be improved by incorporating lubricants or slip agents into blends made from polymers of the invention. All of these additives are generally used in relatively small amounts, usually less than 3 weight percent of the final composition.
The mixture of the polylactide and the polar monomer, oligomer, or polymer is subjected to mechanical deformation in a suitable mixing device, such as a Bradender Plasticorder, a roll mill, a single or multiple screw extruder, or any other mechanical mixing device which can be used to mix, compound, process or fabricate polymers. A particularly desirable reaction device is an extruder having one or more ports. In a preferred embodiment, the reaction device is a co-rotating, twin-screw extruder, such as a ZSK-30 twin-screw compounding extruder manufactured by Werner & Pfleiderer Corporation of Ramsey, N.J. This extruder allows multiple feeding and venting ports.
The presence of PLA or modified PLA in blends used to make fibers, films or other shapes reduces the water sensitivity of pure PVOH in use. PLA grafted with a polar monomer or a mixture of monomers is preferred for enhanced compatibility with PVOH in order to obtain superior processing and mechanical and physical properties. It is possible to use the blends to make other shapes than fibers or films and to thermally form the blends into complex shapes.
As used herein, the term "water-dispersible" means that the composition dissolves or breaks into pieces smaller than a 20 mesh after being immersed in water for approximately five minutes. The term "water-disintegratable" means that the composition breaks into multiple pieces within five minutes of immersion in water and that some of the pieces will be caught by a 20 mesh screen without slipping through in the same manner as a thread through the eye of a needle. The term "water-weakenable" means that the composition remains in one piece but weakens and loses rigidity after five minutes of immersion in water and becomes drapeable, i.e. it bends without an external force applied thereto when it is held by one side at a horizontal position. The term "water-stable" means that the composition does not become drapeable after five minutes of immersion in water and remains in one piece after the water response test.
As used herein, the term "graft copolymer" means a copolymer produced by the combination of two or more chains of constitutionally or configurationally different features, one of which serves as a backbone main chain, and at least one of which is bonded at some point(s) along the backbone and constitutes a side chain. The molar amount of grafted monomer, oligomer or polymer, i.e. side-chain species, may vary but should be greater than molar amount of the parent species. The term "grafted" means a copolymer has been created which comprises side chains or species bonded at some point(s) along the backbone of a parent polymer. The term "blend" as applied to polymers means an intimate combination of two or more polymer chains of constitutionally or configurationally different features which are not bonded to each other. Such blends may be homogenous or heterogeneous. (See Sperling, L. H., Introduction to Physical Polymer Science 1986 pp. 44-47 which is herein incorporated by reference in its entirety.) Preferably, the blend is created by combining two or more polymers at a temperature above the melting point of each polymer.
The present invention is illustrated in greater detail by the following specific Examples. It is to be understood that these Examples are illustrative embodiments and that this invention is not to be limited by any of the Examples or details in the description. Rather, the claims appended hereto are to be construed broadly within the scope and spirit of the invention.
EXAMPLES
Example 1
Reactive-Extrusion of Polylactide with HEMA
A co-rotating, twin-screw extruder, ZSK-30 manufactured by Werner & Pfleiderer Corporation of Ramsey, N.J. was used to manufacture the modified PLA of the Examples. The diameter of the extruder was 30 mm. The length of the screws was 1388 mm. This extruder had 14 barrels, numbered consecutively 1 to 14 from the feed hopper to the die. The first barrel, barrel #1, received the PLA and was not heated but cooled by water. The vinyl monomer, HEMA, was injected into barrel #5 and the Lupersol 101 peroxide by Atochem was injected into barrel #6. Both the monomer and the peroxide were injected via a pressurized nozzle injector. A vacuum port for devolatilization was included at barrel #11. The die used to extrude the modified PLA strands had four openings of 3 mm in diameter which were separated by 7 mm. The modified PLA strands were then cooled in a cold water bath and then pelletized.
The PLA was fed into the extruder with a volumetric feeder at a throughput of 20 lb/hr. The HEMA and the peroxide were injected into the extruder at throughputs of 1.8 lb/hr and 0.09 lb/hr, respectively. The screw speed was 300 rpm.
The following extruder barrel set temperatures were used during the extrusion run:
______________________________________Zone 1 Zone 2 Zone 3 Zone 4 Zone 5 Zone 6 Zone 7______________________________________180° C. 180° C. 180° C. 180° C. 180° C. 170° C. 160° C.______________________________________
The vacuum was turned on for devolatization at barrel #11 and the process was allowed to stabilize. The extruded HEMA grafted PLA (PLA-g-HEMA) strands were cooled in a cold water bath and then pelletized.
Melt rheology tests were performed on the modified and unmodified PLA on a Goettfert Rhoegraph 2000 available from Goettfert in Rock Hill, S.C. The modified PLA of this Example was prepared with 9 weight percent HEMA and 0.45 weight percent Lupersol. The weight percentages of the HEMA and Lupersol were based on the weight of the PLA.
The melt rheology tests were performed at 180° C. with a 30/1 (length/diameter) mm/mm die. The apparent melt viscosity was determined at apparent shear rates of 50, 100, 200, 500, 1000, and 2000 l/s. A rheology curve was plotted for each material of the apparent viscosity versus the apparent shear rates below.
______________________________________ PLA-g-HEMASample PLA, Aldrich (9%, 0.45%)______________________________________Comment Extruded Control Grafted PLAApp. Shear Rate App. Shear Visc. App. Shear Visc.(l/s) (Pa s) (Pa s)49.997 325.7 97.7199.994 252.42 97.71199.99 207.63 65.14499.97 154.71 55.3691000 112.35 46.4072000 82.235 38.675______________________________________
The apparent melt viscosities at the various apparent shear rates were plotted and rheology curves for the unmodified PLA and the modified PLA of the above Example were generated as shown in FIG. 2. The rheology curve of the modified PLA demonstrates the reduced viscosities of the modified PLA when compared to the unmodified PLA. These reduced viscosities of the modified PLA result in improved processability of the PLA. The grafting of polar monomers, oligomers or polymers onto PLA results in improved compatibility with both polar materials and polar substrates.
Example 2
Fibers Made From Blends Comprising PVOH and Modified PLA or Unmodified PLA
The water-responsive fibers of the following Example are comprised of a melt blend of polyvinyl alcohol (PVOH) and either unmodified PLA or PLA as modified in Example 1. The range of the compositions for water-responsive fibers varies from 1 to 99 weight percent of unmodified or modified PLA in the blend. The modified PLA used in the blends is as described above in Example 1 and the unmodified PLA used in the blends was that as supplied by Aldrich Chemical Company. The PVOH used in the blends was Ecomaty AX10000 supplied by Nippon Gohsei, Japan and is a cold-water soluble polymer synthesized from partially hydrolyzed polyvinyl acetate and containing side chain branches. The melt flow rate of the PVOH used was 100 g/10 min. at 230° C. and 2.16 kg.
Extrusion Process for Polymer Blending
Water-responsive blend compositions were prepared by a melt extrusion process. It is preferred to blend or mix the two components in an extruder such as a twin-screw or even a single screw extruder under appropriate temperature and shear/pressure conditions. The blending process can also be performed in a batchwise mixing device, such as a melt mixer or a kneader, which is discussed in the next section. Both PVOH and unmodified or modified PLA can be fed to an extruder either simultaneously or in sequence to minimize any adverse effects on the polymers such as degradation or discoloration.
In this Example, the extrusion process of the blends was performed using a Haake TW-100, a counter-rotating, twin screw extruder. The extrusion set temperatures for the four heating zones were 170, 180, 180 and 168° C. The screw speed was 150 rpm. A resin mixture of PLA or modified PLA and PVOH was fed into the extruder at a rate of 10 lb/hr. The melt was extruded, air-cooled and then pelletized.
Extruded blend compositions which contained 20, 30, and 40 weight percent of either PLA or modified PLA of Example 1 and 80, 70, and 60 weight percent PVOH, respectively, were produced and used for fiber-spinning.
Melt Mixing Process for Polymer Blending
Water-responsive blend compositions were also prepared by a melt mixing process. In this Example, the melt mixing process was performed using a Haake Rheomix® 600, a counter-rotating, twin roller mixer. The mixer set temperature was 180° C. The screw speed was 150 rpm. 70 grams of total resin mixture was fed into the mixer and blended for five minutes. The melt was removed from the mixer and then cooled in air.
Melt mixer compositions which contained 50 and 60 weight percent of either PLA or modified PLA of Example 1 and 50 and 40 weight percent of PVOH were produced and used for fiber-spinning.
Fiber Processing of the Blends
The fibers were made on a small-scale fiber spinning processing equipment. The device consists of a vertically mounted cylinder heated by cartridge heaters. A vertically mounted Worm Gear Jactuator (Model: PKN-1801-3-1, manufactured by Duff-Northon Company, Charlotte, N.C.) was used to extrude the materials into fibers.
The fibers were spun from a spin plate with 3 openings of 0.356 mm. The fibers exiting the die were wound on a drum having both reciprocating and rotary movements to collect fiber samples.
Fibers were prepared with varying amounts of PVOH and the unmodified PLA or modified PLA of Example 1.
Example A) PLA/PVOH 20/80 weight ratio fibers.
The temperature of the cylinder was set at 360° C. At this temperature, soft fibers were made from this polymer blend which was comprised of unmodified polylactide and polymer vinyl alcohol. The fibers were slightly yellowish.
Example B) PLA-g-HEMA/PVOH 20/80 weight ratio fibers.
This sample was made from the HEMA grafted PLA and polyvinyl alcohol. The temperature of the barrel was also set at 360° C. This polymer blend was made into fibers of less color than the fibers made from the unmodified blend above. These fibers were nearly colorless. This polymer blend exhibited substantially higher melt strength than the blend containing unmodified PLA, presumably due to the improved compatibility of the HEMA grafted PLA with PVOH. As a result, the fibers could be extruded at a higher extrusion rate than those from the blends containing unmodified PLA. Fibers could be produced in a temperature range from 353 to 371° C.
Example C) PLA/PVOH 30/70 weight ratio fibers.
This blend composition was also spun into fibers. Some melt fracture occurred.
Example D) PLA-g-HEMA/PVOH 30/70 weight ratio fibers.
Soft and nearly colorless fibers were made from this blend composition. This blend showed improved processability over the unmodified PLA/PVOH 30/70 blend.
Example E) PLA/PVOH 40/60 weight ratio fibers.
Example F) PLA-g-HEMA/PVOH 40/60 weight ratio fibers.
Example G) PLA/PVOH 50/50 weight ratio, mixer blended fibers.
Example H) PLA-g-HEMA/PVOH 50/50 weight ratio, mixer blended fibers.
Example I) PLA/PVOH 60/40 weight ratio, mixer blended fibers.
Example J) PLA-g-HEMA/PVOH 60/40 weight ratio, mixer blended fibers.
The blends containing HEMA grafted PLA had lower viscosities than the blends containing unmodified PLA and thus could be extruded at higher rates and exhibited improved processability. Additionally, the fibers from the blends containing modified PLA exhibited less discoloration than fibers from the blends containing unmodified PLA, suggesting improved compatibility of the modified PLA. All of the blends containing HEMA grafted PLA exhibited higher melt strength and better fiber processability than those containing unmodified PLA blends at the same weight ratios.
Water Response Test of the HEMA grafted PLA/PVOH Fibers
For each of the above compositions, a section of the prepared fiber was cut measuring about one inch long. The diameter of the fiber was measured and recorded. The water-response test involved using a pair of tweezers to hold the section of the fiber, immersing it into a scintillation vial filled with 20 milliliters of water and holding it there for five minutes. After five minutes, the cap was placed on the scintillation vial and the vial was placed in a Model 75 Shaker (available from Burrell Corp., Pittsburgh, Pa.). The vial was shaken for 30 seconds with the shaker set at maximum speed. If the fiber began to disperse or disintegrate, the contents of the scintillation vial were emptied through a 20 mesh screen (20 mesh U.S.A. Standard Testing Sieve, ASTM E-11 Specification, No. 20). The vial was then rinsed with 20 milliliters of water from a squeeze bottle to remove any remaining fiber pieces and emptied through the sieve. If the fiber did not disperse or disintegrate, the fiber was observed for any loss in rigidity.
______________________________________Water Response Map for Extruder and MixerBlended Fiber CompositionsWeight Percent of unmodified or modified PLAin Blends with PVOH______________________________________1 <-------------> 40 50 60 <-------------> 99Dispersible Weakenable Stable______________________________________
Fibers made from blend compositions were water-dispersible up to about 40 weight percent of modified or unmodified PLA in the blend. The fibers made from blends with about 60 or greater weight percent of unmodified or modified PLA were water-stable. The fibers made from blends between these two ranges should be considered water-weakenable. The fibers made from blends with about 50 weight percent of unmodified or unmodified PLA were water-weakenable.
Example 3
Films Made From Blends Comprising PVOH and Modified PLA or Unmodified PLA
The water-responsive films of the following Examples are composed of melt blends of unmodified or modified PLA and PVOH. The range of the compositions for water-responsive films vary from 1 to 99 weight percent of unmodified or modified PLA in the blend. The presence of PLA or modified PLA in the blend used to make films reduces the water sensitivity of pure PVOH in use. PLA grafted with a polar monomer or a mixture of monomers is preferred for enhanced compatibility with PVOH in order to obtain superior mechanical and physical properties. The modified PLA used in the blends is as described above in Example 1 and the unmodified PLA used in the blends was that as supplied by Aldrich Chemical Company. The PVOH used in the blends was Ecomaty AX10000 supplied by Nippon Gohsei, Japan, a cold-water soluble polymer synthesized from partially hydrolyzed polyvinyl acetate containing side branches.
Extrusion Process for Polymer Blending
Water-responsive blend compositions were prepared by a melt extrusion process. It is preferred to blend or mix the two components in an extruder such as a twin-screw or even a single screw extruder under appropriate temperature and shear/pressure conditions. The blending process can also be performed in a batchwise mixing device, such as a melt mixer or a kneader, which is discussed in the next section. Both PVOH and modified PLA can be fed to an extruder either simultaneously or in sequence to minimize any adverse effects on the polymers such as degradation or discoloration.
In these Examples, the extrusion process of the blends was performed using a Haake TW-100, a counter-rotating, twin screw extruder. The extrusion set temperatures for the four heating zones were 170, 180, 180 and 168° C. The screw speed was 150 rpm. A resin mixture of PLA or modified PLA and PVOH was fed into the extruder at a rate of 10 lb/hr. The melt was extruded, air-cooled and then pelletized.
Extruded blend compositions which contained 20, 30, and 40 weight percent of either unmodified PLA or modified PLA and 80, 70 and 60 weight percent PVOH, respectively, were produced and used to make films in this Example.
Melt Mixing Process for Polymer Blending
Water-responsive blend compositions were also prepared by a melt mixing process. In these Examples, the melt mixing process was performed using a Haake Rheomix® 600, a counter-rotating, twin roller mixer. The mixer set temperature was 180° C. The screw speed was 150 rpm. 70 grams of total resin mixture was fed into the mixer and blended for five minutes. The melt was removed from the mixer and then cooled in air.
Melt mixer compositions containing 30, 40, 50 and 60 weight percent HEMA grafted PLA and 70, 60, 50 and 40 weight percent PVOH, respectively, were produced and used to make the films in this Example.
Film Preparation
A film was prepared for each blend composition using a Carver hot press with two heated platens at a temperature of 190° C. and a pressure of 15,000 psi for about one minute. The thickness of the films in this Example were approximately 4 mils. However, the thickness of the films could be either increased or decreased depending on the final use and properties desired.
Water Response Test of the HEMA grafted PLA/PVOH Films
For each of the compositions, a section of the prepared film was cut measuring about 1/4 of an inch by about 1/2 of an inch. The water-response test involved using a pair of tweezers to hold the section of the film, immersing it into a scintillation vial filled with 20 milliliters of water and holding it there for five minutes. After five minutes, the cap was placed on the scintillation vial and the vial was placed in a Model 75 Shaker (available from Burrell Corp., Pittsburgh, Pa.). The vial was shaken for 30 seconds with the shaker set at maximum speed. If the film began to disperse or disintegrate, the contents of the scintillation vial were emptied through a 20 mesh screen (20 mesh U.S.A. Standard Testing Sieve, ASTM E-11 Specification, No. 20). The vial was then rinsed with 20 milliliters of water from a squeeze bottle to remove any remaining film pieces and emptied through the sieve. If the film did not disperse or disintegrate, the film was observed for any loss in rigidity.
______________________________________Water Response Map for Extruder and MixerBlended Film CompositionsWeight Percent of unmodified or modified PLAin Blends with PVOH______________________________________1 <-------------> 40 50 60 <-------------> 99Dispersible Weakenable Stable______________________________________
Films made from blend compositions were water-dispersible up to about 40 weight percent of modified or unmodified PLA in the blend. The films made from blends with about 60 or greater weight percent of unmodified or modified PLA were water-stable. The films made from blends between these two ranges should be considered water-weakenable. The films made from blends with about 50 weight percent of unmodified or unmodified PLA were water-weakenable.
It is to be understood that these Examples are illustrative embodiments and that this invention is not to be limited by any of the Examples or details in the description. Rather, the claims appended hereto are to be construed broadly within the scope and spirit of the invention. Particularly, it is to be understood that the invention include multilayer films and fibers or articles in which the claimed film or fiber is a layer in the final product. | The present invention is a hydrolytically modified, biodegradable polymer and a method of hydrolytically modifying a biodegradable polymer. In a preferred embodiment, the invention is a method of grafting polar groups onto polylactides and modified polylactide compositions produced by the method. The polymer compositions are useful as components in flushable and degradable articles. | 2 |
FIELD OF THE INVENTION
[0001] This invention relates to two attenuated strains of porcine reproductive and respiratory syndrome virus (PRRSV) and immunogenic compositions comprising one or more strains of attenuated porcine reproductive and respiratory syndrome virus (PRRSV).
BACKGROUND OF THE INVENTION
[0002] PRRS was recognized for the first time in the United States in 1987. It quickly spread throughout all of the major swine producing areas of North America. It next appeared in Europe, and today PRRSV has almost worldwide distribution. Many swine producers, government officials, and veterinarians believe that PRRS is currently one of the most serious economic threats faced by the swine industries worldwide.
[0003] As its name implies, PRRS is characterized clinically by its ability to cause reproductive failure in pregnant females, especially when initially infected late in gestation, and respiratory tract illness in pigs of all ages, but most common and severe in young pigs. A PRRSV infection is also thought to potentiate the effects of other swine pathogens. On the basis of retrospective serological studies, it also has become evident that many infections of swine with PRRSV are either subclinical or result in less obvious clinical signs. Therefore, the PRRSV often gains access to a herd and spreads extensively before its presence is first detected.
[0004] The virus can persist in an infected host for at least several months. Such “carriers” perpetuate the infection and make control of the disease extremely difficult. As a consequence, the most effective means for reducing the economic impact of PRRSV is to vaccinate (immunize) potentially susceptible pigs before they are exposed to virulent field virus.
[0005] Attenuated vaccines, (manufactured by Boehingher Ingelheim) prepared from single strains of PRRSV, are commercially available. One is licensed for use in pigs between 3 and 18 weeks of age for the prevention of respiratory tract illness (Gorcyca et al., 1995). One is licensed for pre-breeding.
[0006] Another attenuated vaccine has been described for the prevention of reproductive failure (Hesse et al., 1996). It is prepared from a single strain of PRRSV and has only been tested against a single strain of PRRSV. The challenge strain is described as heterologous on the basis of the anamnestic response of vaccinated gilts following challenge; however, no other evidence has been presented to establish that the two strains, i.e., the one used for the vaccine and the one used for challenge of immunity, are genetically or antigenically different.
[0007] There are two known major serotypes of PRRSV (Done et al., 1996). One (prototype Lelystad) is representative of at least most strains that have been isolated in Western Europe. The other (prototype ATCC 2332) is representative of at least most strains isolated in North America and Asia. There also are antigenic variants within prototypes (Meng et al., 1995), and base sequence differences among strains isolated in North America have allowed for their differentiation (Wesley et al., 1996).
SUMMARY OF THE INVENTION
[0008] An object of the present invention is to provide an immunogenic composition which protects a pig against clinical disease caused by PRRSV. The immunogenic compositions were derived from two strains of PRRSV that were isolated in the United States from pigs affected with PRRSV.
[0009] Another object of the invention is to provide attenuated strains of PRRSV that would be useful in a polyvalent vaccine against PRRS.
[0010] The present invention is not limited to the expressed objects above, as other objects and advantages of this invention will become readily apparent from the ensuing description.
DEPOSIT OF BIOLOGICAL MATERIAL
[0011] Attenuated strains PP5 and LC13 were deposited on Nov. 4, 2004 under the terms of the Budapest Treaty at the American Type Culture Collection in Manassas, Va. and have been assigned Accession Nos. ATCC PTA-6282 and ATCC PTA-6281, respectively. Pursuant to 37 C.F.R. §1.808, the biological material is made under two conditions. First, access to the deposit will be made available during pendency of the patent application making reference to the deposit to one determined by the Commissioner to be entitled thereto under 37 C.F.R. §1.14 and 35 U.S.C. §122; and secondly with one exception, that restrictions imposed by the depositor on the availability to the public of the deposited material be irrevocably removed upon the granting of the patent.
DETAILED DESCRIPTION OF THE INVENTION
[0012] “Immunogenic composition” is defined herein in its broad sense to refer to any type of biological agent in an administratable form capable of stimulating an immune response in an animal. For purposes of this invention, the immunogenic composition may comprise as the viral agent either the virus itself or an immunogenic (antigenic) component of the virus.
[0013] The immunogenic composition of the invention was prepared from any one or more of the two attenuated strains of PRRSV: PP5 and LC13. Each strain was individually tested for safety and ability to induce and immune response, and it is contemplated that a polyvalent vaccine comprised of the two strains would be at least as safe and effective as each monovalent composition and might provide even broader immunity to virulent field strains of PRRSV.
[0014] Two strains of PRRSV (strains PP5 and LC13) were selected for development as immunogenic compositions and vaccines.
PRRSV Strain PP5
[0015] A virulent isolate of PRRS virus was obtained from tissue samples from a diseased pig. A tissue homogenate from the diseased pig was inoculated onto primary alveolar macrophages and the presence of virus was detected by cytopathic effects on inoculated but not control cultures. The isolated virus was subsequently demonstrated by reactivity with monoclonal antibodies specific for the PRRS virus by indirect immunofluorescence. 96-well plates of confluent Marc145 cells were fixed with 80% acetone for 10 minutes at 2 days after infection with the virus. Monolayers were then incubated with SDOW17 or VO17 monoclonal antibodies. Following washing, monoclonal antibody reactivity with each virus was detected by incubation with fluorescein isothiocyanate conjugated anti-mouse IgG followed by washing and examination for fluorescence by microscopy. Positive fluorescence was noted with both monoclonal antibodies for the PP5 virus. The PP5 virus was attenuated by serial passage in tissue culture. The virus was initially passed by inoculation of primary swine alveolar macrophage (SAM) cultures (for the first passage) and then by serial passage on Marc145 cells for a total of 81 passages. During this process, virus clones were isolated by plaque purification and characterized for phenotypic properties. The immunogenic composition clone PP5 was selected for impaired growth on swine alveolar macrophages and lack of disease induction in piglets and pregnant sows. The PP5 was expanded on Marc145 cells and frozen as a master seed virus.
[0016] PP5 can be differentiated from other isolated attenuated PRRSV strains by the ORF5 region of its sequence. The PP5 ORF5 sequence is represented by SEQ ID No.:1.
PRRSV Strain LC13
[0017] A virulent isolate of PRRS virus was obtained from tissue samples from a diseased pig. A tissue homogenate from a diseased pig was inoculated onto primary alveolar macrophages and the presence of virus detected by cytopathic effects on inoculated but not control cultures. The isolated virus was subsequently demonstrated to be reactive with monoclonal antibodies specific for the PRRS virus by indirect immunofluorescence. 96-well plates of confluent Marc145 cells were fixed with 80% acetone for 10 minutes at 2 days after infection with the virus. Monolayers were then incubated with SDOW17 or VO17 monoclonal antibodies. Following washing, monoclonal antibody reactivity with each virus was detected by incubation with fluorescein isothiocyanate conjugated anti-mouse IgG followed by washing and examination for fluorescence by microscopy. Positive fluorescence was noted with both monoclonal antibodies for the LC13 virus. The LC13 virus was attenuated by serial passage in tissue culture. The virus was initially isolated in primary swine alveolar macrophage cultures and then was serially passaged on Marc145 cells for a total of 67 passages. During this process, virus clones were isolated by plaque purification and characterized for phenotypic properties. The immunogenic composition clone (LC13) was selected for impaired growth on swine alveolar macrophages and lack of disease induction in piglets and pregnant sows. The LC13 was expanded on Marc145 cells and frozen as a master seed virus.
[0018] LC13 can be differentiated from other isolated attenuated PRRSV strains by the ORF5 region of its sequence. The LC13 ORF5 sequence is represented by SEQ ID No.:2.
[0019] The composition virus or viruses were prepared for administration by formulation in an effective immunization dosage with a pharmaceutically acceptable carrier or diluent, such as physiological saline or tissue culture medium. The expression “effective amount” is defined as being that amount which will induce immunity in a pig against challenge by a virulent strain of PRRSV. Determination of actual dosage amounts would be fully within the skill of a person in the art. Based on the examples given below, it is contemplated that one embodiment is a single dosage of approximately 10 4.5 TCID 50 /ml .
[0020] The compositions can be administered orally, oronasally or by injection. Appropriate adjuvants as known in the art may be included in the composition formulation. As previously mentioned, the subject immunogenic compositions or vaccines may be used individually, or they may be combined together in any combination in the formulation of a polyvalent composition.
[0021] The following examples are used to illustrate successful attainment of the objectives of the invention. None are intended to limit its scope of applicability.
EXAMPLES
[0022] An immunogenic composition was prepared using MARC145 as the substrate (however alternate cell lines that support the growth of PRRS virus such as MA104 cells can also be used). MARC145 cells were grown to confluency in suitable tissue culture vessels (i.e. 850 cm 2 roller bottles) using Eagle's minimum essential media (EMEM) containing 5 to 10% fetal bovine serum, 2 mM L-glutamine, and antibiotics (such as 30 μg/ml gentamicin). Alternate tissue culture media that can support the growth of MARC145 cells such as Dulbecco's modified essential media [DMEM], Medium 199, or others can also be used. Confluent monolayers of MARC145 cells were inoculated with PP5 or LC13 at a multiplicity of infection (MOI) of 1:10 (MOI's in the range of 1:5 to 1:1000 can be used). Following incubation for three to five days at 37° C., culture supernatant fluids were harvested by decanting.
[0023] Virus fluids were titered by making serial dilutions in EMEM supplemented as above and inoculation of 0.2 ml per well into at least four replicate wells of confluent MARC145 or MA104 cells in a 96-well tissue culture plate. Cultures were incubated for five days at 37° C., 3-5% CO 2 in a humidified chamber and observed for cytopathic effects. Titers (50% endpoints) were calculated according to the methods of Spearman and Karber.
[0024] For the preparation of a killed immunogenic composition or killed vaccine formulation, virus fluids were incubated with a chemical inactivation agent such as formaldehyde, glutaraldehyde, binary ethyleneimine, or beta-propiolactone. Virus fluids were then stored at 4° C. until formulated into immunogenic composition. Immunogenic composition was prepared by mixing virus fluids (containing 10 5 to 10 9 TCID 50 of virus; based on pre-inactivation titers) with a physiologically acceptable diluent (such as EMEM, Hank's Balanced Salt Solution®, phosphate buffered saline) and an immune-stimulating adjuvant (such as mineral oil, vegetable oil, aluminum hydroxide, saponin, non-ionic detergents, squalene, or other compounds known in the art, used alone or in combination). An immunogenic composition dose was typically between 1 and 5 ml.
[0025] For a live immunogenic composition or live vaccine formulation, virus fluids (attenuated virus) are stored frozen at −50° C. or colder until use. Virus fluids (typically containing 10 6.0 TCID 50 /dose but within the range of 10 3.0 and 10 7.0 TCID 50 /dose) are diluted with a physiologically suitable diluent (such as EMEM, Hank's Balanced Salt Solution®, phosphate buffered saline) and a physiologically suitable mixture of compounds designed to stabilize the virus. Compounds known in the art that can be used alone or in combination to stabilize viruses include sucrose, lactose, N-Z amine, glutathione, neopeptone, gelatin, dextran, and tryptone. Vaccine is stored frozen (−50° C. or colder) or lyophilized with storage at 4° C. until use. The immunogenic composition or vaccine typically has a dose size of 2 ml (range of 1 to 5 ml).
[0026] For prophylaxis against PRRS-induced disease, swine are vaccinated with live or killed immunogenic composition by intradermal, intramuscular, subcutaneous, intranasal, or oral administration of one dose of vaccine. A booster vaccination may be administered two to four weeks after the initial immunization. For the prevention of PRRS associated disease, the vaccination regimen is typically initiated up to 6 weeks prior to breeding and can be given as late a one week after breeding. For the prevention of respiratory disease in piglets, vaccination may be given as early as 3 weeks of age.
[0000] Examples of Strain Attenuation and their Ability to Induce Immune Response
PP5 Experiment
[0027] PRRS seronegative sows at 85 days gestation were inoculated intranasally (3 ml/nare) with the master seed vaccine strains PP5 (10 4.5 TCID 50 /ml). All sows farrowed at their expected time.
[0028] Table 1 provides the results for the PP5 PRRS virus strain experiment. The first group PP5-WT is the wild type virus or virulent/disease control. Group PP5-MSV is the master seed virus of the attenuated PP5 strain. PP5-BP represents the fifth backpassage (pig passage) from PP5-MSV to see if the any reversion to wild type virus takes place.
[0029] The results from the PP5 experiment are summarized in Table 2. PP5-WT caused parturition mortality of 69% compared to PP5-MSV and PP5-BP only having caused 16% parturition mortality to 19% parturition mortality, respectively.
[0000]
TABLE 1
PP5
Sow
Elisa
% Mortality @
Group
#
Antibody
Birth
PP5-WT
40
NT
100%
PP5-WT
165
0.9
85%
PP5-WT
313
1.3
67%
PP5-WT
1138
1.2
25%
PP5-WT
1156
1.2
45%
PP5-WT
69%
Totals
PP5-MSV
1344
0.511
20%
PP5-MSV
1347
0.002
0%
PP5-MSV
1348
1.005
40%
PP5-MSV
1350
1.151
15%
PP5-MSV
1353
0.899
0%
PP5-MSV
1355
1.188
13%
PP5-MSV
16%
Totals
PP5-BP
1345
0.932
38%
PP5-BP
1346
0.56
13%
PP5-BP
1349
0.515
33%
PP5-BP
1351
0.569
0%
PP5-BP
1352
1.174
27%
PP5-BP
1354
0.624
0%
PP5-BP
19%
Totals
[0000]
TABLE 2
Summary of PP5
% Mortality @
Birth
Wild Type Virus
69%
PP5-WT
Master Seed Virus
16%
PP5-MSV
Back Passage Virus
19%
PP5-BP
LC13 Experiment
[0030] PRRS seronegative sows at 85 days gestation were inoculated intranasally (3 ml/nare) with the master seed vaccine strain LC13 (10 4.5 TCID 50 /ml). All sows farrowed at their expected time.
[0031] Table 3 provides the results for the LC13 PRRS virus strain experiment. The first group LC13-WT is the wild type virus or disease/virulent control. Group LC13-MSV is the master seed virus of the attenuated LC13 strain. LC13-BP represents the fifth backpassage (pig passage) from LC13-MSV to see if the any reversion to wild type virus takes place.
[0032] The results from the LC13 experiment are summarized in Table 4. LC-WT caused parturition mortality in 86% of the piglets, whereas LC13-MSV and LC13-BP only caused 12% parturition mortality to parturition 15% mortality, respectively.
[0000]
TABLE 3
LC13
Sow
Elisa
% Mortality @
Group
#
Antibody
Birth
LC13-WT
187
1.3
75%
LC13-WT
309
NT
100%
LC13-WT
518
0.8
100%
LC13-WT
858
1.2
88%
LC13-WT
1041
1.2
56%
LC13-WT
86%
Totals
LC13-MSV
843
1.0
0%
LC13-MSV
845
0.7
8%
LC13-MSV
846
0.0
0%
LC13-MSV
848
1.1
25%
LC13-MSV
850
1.0
11%
LC13-MSV
12%
Totals
LC13-BP
844
<0.1
0%
LC13-BP
847
<0.1
31%
LC13-BP
849
<0.1
10%
LC13-BP
851
<0.1
11%
LC13-BP
853
<0.1
0%
LC13-BP
13%
Totals
[0000]
TABLE 4
Summary of LC13
% Mortality ®
Birth
Wild Type Virus
86%
LC-13-WT
Master Seed Virus
12%
LC13-MSV
Back Passage Virus
13%
LC13-BP
[0033] The enzyme-linked immunosorbent assay (Elisa) antibody data found in Tables 1 and 3 represents the results from an Elisa antibody assay on the saws. ELISA is the most commonly used test for detecting antibodies against PRRS. The HerdChek PRRS ELISA manufactured by IDEXX Laboratories Inc. is for detection of anti-PRRSV nucleocapsid (N) protein antibodies from swine serum or plasma. Test results were determined based on the Sample/Positive (S/P) values: positive=S/P ratio >0.4, negative=S/P ratio <0.4. As the results show in Table 1 and 3, both LC13-MSV and PP5-MSV raised antibodies for PRRS. This data generated provides evidence of an immunogenic composition.
[0034] The data presented in this application clearly demonstrates that the attenuated PRRS virus strains PP5 and LC13 are both safe and induce an immune response. | This invention relates to two attenuated strains of porcine reproductive and respiratory syndrome virus (PRRSV) and immunogenic compositions comprising one or more strains of attenuated porcine reproductive and respiratory syndrome virus (PRRSV). | 0 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a process for producing an improved modified plant protein having thermoplastic and forming properties similar to casein and caseinate salts. The process involves the reaction of an alkali metal carbonate with plant protein to produce a reaction product. Peroxide is then added to the reaction product and the peroxide containing reaction product is then neutralized. The reaction product is then heated under a vacuum.
2. Description of the Prior Art
Casein, a milk protein, and its salts are used extensively in the food industry to manufacture fabricated food products. One of the major reasons for the popularity of casein and caseinate salts in fabricated foods is its unique functional properties such as high water solubility and the thermoplastic behavior of caseinate-water mixtures. By thermoplastic behavior, in this context, is meant the ability of a protein dough to flow freely like a liquid upon application of heat and a return to a semi-solid elastic mass upon cooling to ambient temperatures. Unmodified plant proteins generally lack this property and therefore cannot be used as a functional replacement of caseinate salts although the cost considerations favor their use. U.S. Pat. Nos. 3,917,877, 3,917,878, 3,917,879, and 3,930,058 have described processes used to modify plant proteins to simulate the thermoplastic properties of casein or caseinate salts. In all of the processes taught in the above patents, unmodified plant protein was treated with alkali. The alkali treatment of plant protein produces a product having a muddy green color and a strong odor characteristic of hydrogen sulfide. It has been observed that the color, odor and flavor of the alkali treated plant protein is highly objectionable and undesirable.
We have now developed a process by which the flavor and color of alkali-modified plant protein can be improved to yield a protein of highly desirable creamy white color and bland flavor. According to the developed process, the alkali-modified solution of plant protein or a mixture of plant and animal protein is reacted with a peroxide solution, followed by removal of steam volatile flavor components. The latter may be accomplished by heating the peroxide treated protein solution under a vacuum and removing the vapors. The relative amount of peroxide added and the time and temperature of peroxide treatment determine the extent of improvement in color, odor and flavor.
SUMMARY OF THE INVENTION
It is an object of this invention to provide a process for producing a modified plant protein with improved odor, taste, and color, having the thermoplastic and binding properties of casein and caseinate salts.
The object of this invention is accomplished by a process for producing a modified plant protein having properties similar to casein and caseinate salts and having improved odor, taste and color, said process comprising:
a. making an aqueous slurry of a vegetable protein material, said plant protein material containing at least about 30 percent by weight protein;
b. adjusting the pH of the aqueous slurry to a pH in the range of from about 7.0 to about 10.5 by addition thereto of an alkali metal carbonate;
c. heating the aqueous slurry to react the alkali metal carbonate with the protein;
d. cooling the slurry to a temperature within the range of from about 60° F. to 130° F.
e. adding from about 0.3 percent to about 2.0 percent by weight peroxide to the slurry per pound of protein;
f. mixing the peroxide containing slurry;
g. neutralizing the slurry to a pH of from 6.6 to 7.0 by addition thereto of an edible acid;
h. thereafter, heating the slurry under a vacuum to remove steam-volatile flavor substances;
i. drying the neutralized slurry to remove a substantial portion of the water therein; and
j. admixing from 1 to 15 parts by weight of the neutralized and modified slurry with from 1-30 parts by weight unmodified proteinaceous material.
The object of this invention is also accomplished by a process for producing a modified plant protein having properties similar to casein and caseinate salts and having improved odor, taste and color, said process comprising:
a. making an aqueous slurry of a vegetable protein material, said plant protein material containing at least about 30 percent by weight protein;
b. adjusting the pH of the aqueous slurry to a pH in the range of from about 7.0 to about 10.5 by addition thereto of an alkali metal carbonate;
c. heating the aqueous slurry to react the alkali metal carbonate with the protein;
d. cooling the slurry to a temperature within the range of from about 60° F. to 130° F.
e. adding from about 0.3 percent to about 2.0 percent by weight peroxide to the slurry per pound of protein;
f. mixing the peroxide containing slurry;
g. neutralizing the slurry to a pH of from 6.6 to 7.0 by addition thereto of an edible acid;
h. thereafter, heating the slurry under a vacuum to remove steam-volatile flavor substances; and
i. admixing from 1 to 15 parts by weight of the neutralized and modified slurry with from 1-30 parts by weight unmodified proteinaceous material.
Preferably, the process includes a cooling step, say down to a range of from about 60° F. to 130° F., after the heating-reacting step and prior to the neutralization step.
More preferably the protein material of this invention is a solvent extracted oil seed vegetable protein.
It is also preferable that the aqueous slurry of this invention has a solids contents of about 3 percent to about 18 percent by weight, and a protein content up to about 12 percent by weight.
The preferred alkali metal carbonate of this invention is a member selected from the group comprising sodium carbonate, sodium bicarbonate, potassium carbonate, and potassium bicarbonate.
The preferred peroxide of this invention is a member selected from the group consisting of hydrogen peroxide, sodium peroxide, potassium peroxide, calcium peroxide and magnesium peroxide.
The preferred reaction temperature of this invention is a temperature of from 280° F. to 370° F. in a closed vessel for 21/2 to 5 minutes.
DETAILED DESCRIPTION OF THE INVENTION
The first step in this invention requires making an aqueous slurry of a plant protein material. Preferably, the protein material is an oil seed, solvent extracted, plant protein such as soy protein isolate or soy protein concentrate. Other proteins, however, such as oat protein, have been found to be highly acceptable for use in this invention. Other oil seed vegetable proteins, solvent extracted to concentrate the protein therein are also acceptable, such as peanut and sesame protein and the other oil seed vegetable proteins. It is preferred that the protein material contain at least about 30 percent by weight protein.
The aqueous slurry is prepared simply by adding the proteinaceous material to water and mixing until a slurry is provided. Preferably the slurry is prepared by mixing from 3 to 18 percent by weight of the proteinaceous material in water and mixing until a slurry is formed. This preferably gives an overall protein content in the slurry of up to about 12 percent by weight.
The next step in the invention requires adjusting the pH of the aqueous slurry to a pH in the range of from about 7.0 to about 10.5 by addition thereto of an alkali metal carbonate. It is important and critical to the invention that the aqueous slurry have a pH above 7.0 in order to carry out the complete process of this invention. This can generally be accomplished by adding from about 0.5 to 4.0 percent by weight of the alkali metal carbonate. By use herein of the term "alkali metal carbonate" it is intended to mean the term with its well known use consisting of the carbonates of the alkali metals as well as the bicarbonates or acid carbonates thereof. For instance, sodium carbonate and potassium carbonate are highly acceptable in this invention as well as sodium bicarbonate and potassium bicarbonate. It is within the purview of one skilled in the art that he might achieve the desired pH range by addition of the carbonate. It is preferable that the pH be adjusted between 7.2 and 10.5. A pH of about 8 is highly preferable.
After the pH has been adjusted by addition of an alkali metal carbonate the aqueous slurry is heated to react the alkali metal carbonate with the protein. The heating must be sufficient to provide a reaction between the carbonate and the protein but must be below the decomposition temperature of the protein. We have found, for instance, that the 330° F. reaction temperature in an enclosed vessel for a time period of from 160-200 seconds produces an acceptable product. We have also found that a temperature from 295° F. to 310° F. for from 3.5 to 5 minutes produces a good product. Other times and temperatures may also be utilized, providing the reaction product when neutralized has the same properties as herein attributed to the above-described reaction. It is well within the skill of one knowledgeable in the art to prepare these different products with different reactions in order to arrive at an end product. However, the optimum conditions are as stated above. In any condition, the temperature should be at least above the boiling point of water up to a point at which degradation of the protein material or reaction product occurs. It is preferable that the reaction be conducted in a closed vessel since this enables heating of the aqueous slurry above the boiling point of water. Generally this will raise the pressure of the reaction to something around 90 pounds per square inch but this is acceptable in producing a desirable product.
At this point in the process, it is preferable to cool the reacted mass. This can be accomplished by conventional means to arrive at a temperature of from about 60° F. to 130° F.
The next step in this invention requires the addition of a peroxide to the slurry. The peroxide containing slurry is then thoroughly mixed. The peroxide can be a member selected from the group consisting of hydrogen peroxide, sodium peroxide, potassium peroxide, calcium peroxide and magnesium peroxide. The relative amount of the peroxide added and the time and temperature of peroxide treatment will determine the extent of improvement in color, odor and flavor. It is preferable that from about 0.3 percent to about 2.0 percent by weight peroxide is added per pound of protein. It is also preferable to add the peroxide to the slurry when the slurry is at room temperature.
The next step in this invention requires the neutralizing of the slurry to a pH of from 6.6 to 7.0 by addition thereto of an edible acid. It is critical that the neutralization produce a pH within the stated range. A much lower pH will cause precipitation of the protein. The neutralization can occur by use of any of the known edible acids which are normally used as food additives. For instance, hydrochloric acid, citric acid, formic acid and acetic acid, are all members of the group of edible food grade acids acceptable for use in this invention.
After the slurry has been neutralized and the peroxide has been added, the slurry is heated to remove the steam volatile flavor components. The removal of the steam volatile flavor components can be accomplished much faster if the slurry is heated under a vacuum, in the range of from about 15 inches to about 30 inches and at a temperature sufficient to accomplish boiling. Preferably, the steam volatile flavor components are removed from the slurry by heating the slurry to a temperature of 150° F. under a vacuum of 22 inches. By use herein of the term "steam volatile flavor components" it is intended to mean those substances that have a boiling point lower than that of water and which impart objectionable flavors and odors to the alkali modified protein.
After neutralization of the slurry and the removal of the steam volatile flavor substances, the slurry is then dried to remove a substantial portion of the water. The moisture content of the final product should be about 15 percent by weight moisture or lower. Drying can occur in any of the common commercial processes such as drum drying, spray drying, or freeze drying, and either process is acceptable for use in this invention.
The final step in this process requires admixing from 1 to 15 parts by weight of the neutralized slurry with from 1 to 30 parts by weight unmodified proteinaceous material. The unmodified proteinaceous material refers to proteinaceous material that is not modified according to the process hereinabove described with relation to modification by alkali metal carbonate treatment. The unmodified proteinaceous material may refer to either plant proteins or animal proteins. In other words, the unmodified proteinaceous material can refer to the oil seed vegetable proteins that are solvent extracted such as soy protein concentrate, soy protein isolate, or it may refer to oat protein, peanut protein, or sesame protein which has been unmodified or it may also refer to meat protein such as meaty materials, or to fish protein such as fish flour or fish meal. In other words, the normally acceptable usage of the term "proteinaceous material" is acceptable for admixture herewith to produce an acceptable product.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
This invention may be more fully described, but is not limited by the following examples.
EXAMPLE 1
An aqueous slurry of approximately 6 percent by weight soy protein isolate was prepared by mixing about twenty pounds of soy protein isolate with about 38 gallons of water at ambient temperature. About 315 grams of sodium carbonate was slowly added to the slurry to achieve a pH of approximately 8.0. The protein slurry was then heated at 300° F. for 4 minutes and cooled to ambient temperature. The resulting protein solution had a muddy green color and a strong odor characteristic of hydrogen sulfide. Two hundred milliliters of 30 percent hydrogen peroxide was added to the material and the contents were mixed for 30 minutes. The pH of the protein solution was adjusted to 7.0 with 1 N hydrochloric acid and the solution was pumped into a single stage vacuum evaporator. The solution was heated at 150° F. under a vacuum of 22 inches, and the resulting vapors were removed. The evaporation was continued until the volume in the evaporator was reduced to approximately half the original volume. The concentrated slurry was yellowish white in color and had a bland flavor and odor. The product was then dried in a spray drier until the moisture content thereof was less than 15 percent by weight. The dried slurry resembled a creamy white powder with bland flavor and odor. The dried slurry was then admixed with unmodified soy protein concentrate in an amount of 3 parts by weight soy protein concentrate to 1 part by weight dried slurry and extruded into a fibrous product having properties similar to casein.
EXAMPLE 2
A procedure similar to that in Example 1 was used except that the pH of the alkali-modified slurry was adjusted to 7.0 before adding hydrogen peroxide.
EXAMPLE 3
Same as Example 1 except that 100 grams of sodium peroxide was mixed with the alkali-modified protein in place.
EXAMPLE 4
Same as Example 2 except that 100 grams of sodium peroxide was added in place of hydrogen peroxide.
EXAMPLE 5
Example 1 is repeated with the exception that the alkali metal carbonate is potassium carbonate. Again, an acceptable product is produced.
EXAMPLE 6
Example 1 is repeated except the modified plant protein material is oat protein. Again, an acceptable product is produced.
EXAMPLE 7
Example 5 is repeated with the exception that the modified plant protein material is oat protein. Again, an acceptable product is produced.
EXAMPLE 8
Example 1 is repeated except the modified plant protein material is a mixture of one part by weight oat protein and two parts by weight soy protein concentrate. Again, an acceptable caseinate replacement is produced.
EXAMPLE 9
Example 1 is repeated except the modified plant protein material is a mixture of one part by weight sesame seed protein and three parts by weight soy protein concentrate. Again, an acceptable caseinate replacement is produced.
EXAMPLE 10
Example 1 is repeated except the modified plant protein material is a mixture of one part by weight peanut protein and one part by weight soy protein concentrate. Again, an acceptable caseinate replacement is produced.
EXAMPLE 11
Example 5 is repeated except the modified plant protein material is a mixture of one part by weight sesame protein and three parts by weight soy protein concentrate. Again, an acceptable caseinate replacement is produced.
EXAMPLE 12
Example 5 is repeated except the modified plant protein material is a mixture of one part by weight peanut protein and three parts by weight soy protein concentrate. Again, an acceptable caseinate replacement is produced.
EXAMPLE 13
Example 1 is repeated with the exception that the unmodified protein is ground meat. Again, an acceptable product is produced, in which the binding characteristics of sodium caseinate are found.
EXAMPLE 14
Example 5 is repeated with the exception that the unmodified protein is ground meat. Again, an acceptable product is produced.
EXAMPLE 15
Example 6 is repeated except the unmodified protein is ground meat. Again, an acceptable product is produced.
EXAMPLE 16
Example 7 is repeated with the exception that the unmodified protein is ground meat. Again, an acceptable product is produced.
EXAMPLE 17
Example 8 is repeated with the exception that the unmodified protein is ground meat. Again, an acceptable product is produced.
EXAMPLE 18
Example 9 is repeated with the exception that the unmodified protein is ground meat. Again, an acceptable sodium caseinate replacement is produced.
EXAMPLE 19
Example 10 is repeated with the exception that the unmodified protein is ground meat. Again, an acceptable caseinate replacement is produced.
EXAMPLE 20
Example 11 is repeated with the exception that the unmodified protein is ground meat. Again, an acceptable sodium caseinate replacement is produced.
EXAMPLE 21
Example 12 is repeated with the exception that the unmodified protein is ground meat. Again, an acceptable sodium caseinate replacement is produced.
While it is not desired to be bound by any particular theory covering the operation of this invention, nevertheless, the following postulate is offered in relation to the use of the peroxide.
We believe the alkali treatment induces at least two types of reactions that contribute towards the objectionable flavor, odor and color of the treated slurry. It is believed that one of these reactions involves the alkali metal carbonates acting on the sulfur-containing amino acids in a protein thereby producing a number of low molecular weight sulfur containing compounds such as hydrogen sulfide and thiols. These compounds and others produced through secondary reactions are normally volatile and impart unacceptable flavor and color to the protein. We further believe that the other reaction occurs in the presence of alkali and at elevated temperatures. Under these conditions proteins react with carbohydrates to produce chemical compounds that impart brown color and objectionable flavor. The compounds produced in both reactions are mostly reducing compounds. Since peroxides are potent oxidizing agents, we believe that a reaction between the peroxide and the reducing compounds from the alkali treatment takes place causing oxidation of compounds that are responsible for objectionable flavor and color. The volatile compounds are removed by evaporation under vacuum while the compounds responsible for color are oxidized to colorless compounds by the peroxide. | A process is disclosed for producing an improved modified plant protein having thermoplastic and forming properties similar to casein and caseinate salts. The process comprises making an aqueous slurry of a plant protein material and an alkali metal carbonate, adjusting the pH, reacting the carbonate with the protein, admixing the slurry with a peroxide, neutralizing the slurry, removing steam volatile flavor components, drying the neutralized slurry, and then blending the dried modified proteinaceous slurry with an unmodified proteinaceous material. The process produces a product which is improved in odor, taste and color. | 0 |
BACKGROUND OF THE INVENTION
The present invention is directed to well strainers or screens, and more particularly concerns a well strainer composed of a plurality of annular filtering elements stacked on top of one another so as to form a cylindrical filtering structure and spaced from one another for use in filtering fluids such as water, oil, and gas, which are extracted from bores or wells.
Typical well strainers or screens are made up of a plurality of annular filter sections or rings stacked one on top of the other and joined together by long threaded rods extending the length of the stack to form a cylindrical strainer. As described, for example, in U.S. Pat. No. 1,705,848, a well screen includes a plurality of ring like concrete sections arranged in superimposed relation and spaced from one another by having each section provided with a series of depending lugs which rest upon the upper surface of the adjoining section, and thereby define a preset, non-adjustable, gap between sections. Similarly, U.S. Pat. No. 3,822,744 discloses a straining tube composed of a plurality of superimposed rings with each ring having circumferentially arranged spacers and supports which determine a preset, non-adjustable, gap between adjacent rings and provide stability to the structure.
In order to accommodate different well bore conditions (soil, clay, or rock), to filter out different sizes of solid particles, and to extract different fluids, it is desirable to be able to adjust the gap between adjacent rings during construction of the well strainer so that one need not stock a variety of different well strainers or screens to suit various conditions. For example, U.S. Pat. No. 4,752,394 discloses a bore screen which is constructed from stacked rings with the space between the rings being adjustable. Each ring is formed on opposite first and second faces with aligned circumferentially spaced bearing pads. The bearing pads on the first face of successive rings contact those on the second face of adjacent rings and serve to space the rings apart. The bearing pads on the first face of each ring are formed with stepped projections and those on the second face of each ring are formed with complimentary stepped recesses. The stepped projections and stepped recesses associated with respective ones of the bearing pads on each ring are configured differently from the step projections and step recesses associated with others of the bearing pads whereby the spacing between adjacent rings is selected during bore screen assembly by rotating one ring relative to another to bring different pairs of bearing pads into contact with one another. In the specific example shown in the patent, the rings may be stacked and clamped together to form a bore screen having either 0.50, 0.75, or 1.0 mm gap between rings. Each of the bearing pads on the rings has a cylindrical central opening for receiving one of the threaded studs which extend through the stack of rings. In order to provide for three positions of adjustability, each ring has six bearing pads.
Although the bore screen of above-described U.S. Pat. No. 4,752,394 provides for a limited amount of adjustability in the gap between rings and, as such, is an improvement over well screens which do not provide for adjustability, this bore screen arrangement suffers from two major drawbacks. First, the gap between rings must be selected prior to assembly of the screen, and cannot be changed without completely disassembling the screen, that is, removing all of the threaded studs and rotating each ring relative to the other. Second, the large number of bearing pads tends to obstruct the flow of fluid between the rings by reducing the effective filtering area.
Hence, there is a need for an improved well strainer which not only allows for adjustment of the gap between adjacent stacked filter segments prior to assembling the stack but also allows for adjustment of the gap between filter segments after assembly and does so without requiring complete disassembly and which does not unduly reduce the effective filtering area of the strainer.
SUMMARY OF THE INVENTION
In accordance with the present invention, a well strainer is provided which provides for adjustment of the gap between adjacent filter segments both during and following assembly of the strainer and which does so while maximizing the effective filtering area.
In accordance with an exemplary embodiment of the present invention, the well strainer includes a plurality of stacked, annular, filter segments with each segment including a plurality of elongate, arcuate, threaded rod receiving slots, ramped bearing surfaces near each slot, and position indicators in the vicinity of the ramped bearing surfaces and slots. The gap between adjacent annular filter segments is selected by rotating one segment relative to the other to a desired position whereat indicator points are received within respective indicator sockets. Ring guides help to keep adjacent rings in true superimposed relation.
In cross-section, each annular filter segment is an elongated wedge having smooth upper and lower surfaces with the exception of a thin flat filtering surface on the upper and lower outer edges of each segment. Each annular filter segment has a convex circular inner surface defining a cylindrical central opening and facilitating flow.
In accordance with a particular embodiment of the present invention, each of the elongate, arcuate, threaded rod receiving slots has a plurality of preset bolt receiving positions in the form of a plurality of spaced, cylindrical enlargements along the length of the slot. Having such preset bolt locations in each elongate, arcuate, rod receiving slot eliminates the need for indicator points and sockets along the edge of the filter segments.
Once the well strainer has been assembled by stacking each of the annular filter segments, one on top of the other in superimposed relation along a common longitudinal axis and securing the stack together by a plurality of threaded rods which extend along the length of the stack, adjustments in the gaps between adjacent filter segments can be made by simply loosening the nuts at one or both ends of the stack to allow the indicator points of one segment to be lifted out of the indicator sockets of an adjacent segment and the relieve the bearing pressure between adjacent segments to allow rotation of one segment relative to the other. There is no need to completely disassemble the well strainer in order to adjust the gap between each of the filter segments.
A principal object of the present invention is the provision of a well strainer which not only provides for adjustment of the gap between filter segments during strainer assembly but which also allows for adjustment of the gap between filter segments after the well strainer has been assembled.
Another object of the present invention is provision of a well strainer which provides for adjustability of the gap between filter segments without substantially obstructing fluid flow between the segments and, thereby, allowing for maximum fluid flow through the strainer.
A still further object of the present invention is the provision of a well strainer which provides for adjustment of the gap between adjacent filter segments so as to accommodate differing well conditions and prevent solid particles from entering the strainer.
Other objects and further scope of the applicability of the present invention will become apparent from the detailed description to follow taken in conjunction with the accompanying drawings wherein like parts are designated by like reference numerals.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side elevation illustration of a bottom hole well strainer in accordance with an exemplary embodiment of the present invention,
FIGS. 2A and 2B are top plan view and bottom plan views respectively, of a filter segment in accordance with another embodiment of the present invention,
FIG. 3 is a top plan view representation of a filter segment in accordance with yet another embodiment of the present invention,
FIG. 4 is a top plan view of a filter segment in accordance with a still further embodiment of the present invention,
FIG. 5 is an enlarged fragmentary perspective representation of a portion of the filter segment of FIGS. 2A and 2B,
FIG. 6 is an enlarged fragmentary upper perspective view illustration of the gap adjustment portion of the filter segment of FIG. 2A,
FIG. 7 is an enlarged fragmentary lower perspective view representation of the gap adjustment portion of the filter segment of FIG. 2B,
FIG. 8 is a vertical section through the center of one of the gap adjustment areas of the filter segment of FIGS. 2A and 2B, and
FIG. 9 is a fragmentary side elevation of one of the gap adjustment portions of the filter segment of FIGS. 2A and 2B as viewed from the interior of the filter section.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
In accordance with an exemplary embodiment of the present invention as shown in FIG. 1 of the drawings, a bottom hole well strainer generally designated by the reference numeral 10 includes a plurality of superimposed annular filter segments or rings 12 held together by a plurality of threaded rods 14 and end nuts 16. The well strainer 10 includes a base 18, such as an end cap, and a top 20, for example, a threaded male adapter which threads into a fluid extraction pipe 22. In a conventional manner, the fluid extraction pipe 22 is connected to a suction pump for extracting fluids from a well bore 24. The upper surface of each of the filter segments 12 is spaced a short distance from the lower surface of an adjacent filter segment so as to provide fluid filtering gaps or spaces 26 between each adjacent filter segments. These filtering spaces or gaps 26 are adjusted to accommodate different well bore conditions and fluids. For example, solid particles such as sand, gravel, or clay are prevented from entering the well strainer 10 and, as such, are filtered from the fluid extracted from the well bore. Suitable filter spacings or gaps range from about 10/1000 to 30/1000 of an inch.
In accordance with one particular example of the present invention, the well strainer is approximately four feet in length and includes between 190 and 200 filter segments held together by three elongate threaded rods and at least six end nuts with each ring having a three inch inner diameter and a three and three-quarter inch outer diameter. Such a well strainer can fit within a four inch pipe or well casing.
Although the exemplary embodiment of FIG. 1 is shown to have an end cap 18 at its base, it is to be understood that both ends of the well strainer 10 may be connected to threaded male adapters so that the well strainer 10 may be located along the length of the extraction pipe 22 as well as at its base.
The well bore 24 may be filled with a granular material 28, such as gravel, following the placement of the well strainer 10 to aid in the prevention of having small particles such as sand or clay come into contact with the filtering spaces 26 between the filter segments 12 and, thus, reduce the possibility of having these filter spacings or gaps 26 clogged and reducing the effective filtering capacity of the well strainer. In the exemplary embodiment shown in FIG. 1 of the drawings, the well strainer is assembled with five elongated threaded rods 14 and, as such, would have filter segments resembling those shown in FIGS. 3 or 4 of the drawings with each segment including five openings, each opening adapted to receive one of the threaded, elongated rods 14.
In accordance with the present invention, it is preferred that the well strainer be assembled using at least three elongated, threaded rods with the number of threaded rods and associated gap adjustment elements being determined by the diameter of the filter segments with larger diameter filter segments requiring more rods and gap adjustment elements. For example, a well strainer made up of filter rings each having a two inch inner diameter and a two and three-quarters inch outer diameter may be assembled using three elongated, threaded rods, for example one-eighth inch stainless steel rods and nuts. Larger size well strainers made up of annular filter segments, having, for example, a six inch outer diameter may require the use of four or more elongated rods, such as, one-eighth inch stainless steel rods and nuts.
It is preferred that the filter segments 12 be constructed of polypropylene having about twenty-five to thirty percent reinforced glass fill. Although polypropylene is the preferred material, other materials such as PVC may be used.
To increase the strength of the assembled well strainer, it is preferred to use a double nut arrangement on each end wherein the elongated threaded rods are inserted through the stack of annular filter segments, a nut on each end of each threaded rod is run down against the upper surface of the upper most filter segment and the lower surface of the lower most filter segment, then the end cap or threaded male adapter is placed over these nuts, and, lastly, another nut is run down on each of the threaded rods and tightened against the exterior surfaces of the threaded male adapter and end cap. This double nut arrangement on each end of the well strainer provides added strength and also allows strainers to be preassembled and shipped in a stacked relation without end caps or threaded male adapters. Final assembly, that is attachment of the well strainer to the fluid extraction pipe via threaded male adapters or the attachment of an end cap, is accomplished at the well site without removing the first set of nuts tightened down against the upper most and lower most filter segments.
As illustrated in FIGS. 2A and 2B of the drawings and in accordance with a particular embodiment of the present invention, an annular filter segment generally designated by the reference numeral 30 is shown to include inner and outer cylindrical surfaces 32 and 34 and upper and lower surfaces 36 and 38. The filter segment 30 includes four elongate, arcuate, threaded rod receiving slots 40, 42, 44, and 46 circumferentially spaced with equal angles between slots. Each of the slots 40-46 extends through the annular filter segment and provides an opening for receiving one of the threaded rods used to assemble the well strainer and allows for angular adjustment of one filter segment relative to another. Each of the slots 40-46 has a radial dimension slightly larger than the diameter of the threaded rods used to assemble the well strainer. For example, slots 40-46 have radial dimensions of five-thirty seconds of an inch if one-eighth inch threaded stainless steel rods are to be used.
With particular reference to FIG. 2A of the drawings, adjacent each of the elongate, arcuate rod receiving slots 40-46 are pairs of elongate, arcuate contact wedges 48 and 50 projecting upwardly from upper segment surface 36. Each contact wedge is not only arcuate in that it lies along a circle having a center coaxial with the center of the annular filter segment but also each contact wedge is high at its center and slopes downwardly toward each end to present an arcuate convex surface projecting upwardly from the upper surface of the filter segment (FIGS. 6, 8, and 9). Since each pair of contact wedges 48 and 50 adjacent each slot 40-46 are of like size and shape, only one pair that is the pair being adjacent the slot 40 will be described in detail below.
On the periphery of upper segment surface 36 and adjacent to each of the radially outward contact wedges 48 are sets of nine locator pin receiving sockets 52 adapted to receive locator pins extending from the lower surface of an adjacent filter segment. These nine locator sockets 52 provide for five different angular positions and three different filter gaps between adjacent filter segments, for example, filter gaps of 10/1000, 20/1000, and 30/1000 of an inch between adjacent filter segments. The five different positions correspond to a first, central position with abutting filter segments stacked one on top another with their slots aligned with each other and the other four positions correspond to two adjustment positions to the right (clockwise) and two adjustment positions to the left (counter-clockwise) of the central directly aligned position.
With reference again to FIG. 2B of the drawings, adjacent each of the slots 40-46 are radially spaced, arcuate, elongate wedge seat pairs 54 and 56 projecting from the lower segment surface 38. Since each of the pairs of wedge seats are of like dimension and shape, only the pair 54 and 56 associated with slot 40 will be described in detail below. Each of the wedge seats 54 and 56 is not only arcuate so as to lie in a circle coaxial with the center of radius of the annular filter segment 30 but also has an arcuate, concave, lower surface which is low at its center and high on each end (FIGS. 7, 8, and 9). This concave lower surface of each of the wedge seats 54 and 56 is dimensioned so as to correspond to and receive the upper convex surface of each of the contact wedges 50 and 48, respectively, when adjacent filter segments are stacked on top of one another with their slots superimposed. Projecting downwardly from the side surface of each wedge seat 54 and 56 adjacent the slot 40 are guide members 58 and 60 which project axially below each of the wedge seats and are adapted to telescopically fit and abut with the inner surface of each of the support wedges 48 and 50 of an adjacent filter segment. These guide members 58 and 60 facilitate axial alignment of adjacent filter segments and insure a truly superimposed relationship.
On the periphery of lower segment surface 38 and adjacent the outer surface of each wedge seat 56 are pairs of spaced, locator pins 62 and 64 which project axially from the lower surface 38. These pairs of locator pins 62 and 64 are adapted to be received within the locator sockets 52 of an adjacent filter segment. The locator pins 62 and 64 provide an indication of the selected angular position and resulting gap between adjacent filter segments and are visible from the exterior of the well strainer. The pairs of locator pins 62 and 64 are spaced from each other and positioned relative to the wedge seats 56 so that, with adjacent filter segments superimposed and having their slots aligned one on top of the other, each of the locator pins 62 and 64 are received within respective third and seventh locator sockets 52, counting locator sockets in a counter-clockwise direction from right to left. In this position, the support wedges and wedge seats are dimensioned so as to provide a 10/1000 of an inch gap between the peripheral upper surface and peripheral lower surface of adjacent filter segments. To adjust the gap between the segments to 20/1000 of an inch, one segment is rotated relative to the other so that locator pins 62 and 64 are positioned in either the second and sixth or fourth and eighth locator sockets 52, again counting sockets from right to left in a counter-clockwise direction. A 30/1000 of an inch gap between adjacent filter segments is selected by rotating one filter segment relative to the other to place locator pins 62 and 64 either the first and fifth or fifth and ninth locator sockets 52, again counting locator sockets from right to left.
The convex support wedges and concave wedge seats are double angle in that they provide for equal gap adjustment between filter segments by rotating one segment relative to the other either to the right or left (clockwise or counter-clockwise) by the same amount. This double angle arrangement is necessary so that the slots of superimposed filter segments are kept in substantial alignment to allow the threaded rods to extend throughout the entire length of the well strainer. For example, to provide a 30/1000 of an inch gap between adjacent filter segments throughout the entire length of the well strainer one needs to first rotate the first overlying filter segment to the right or clockwise relative to the base segment, and then rotate the next superimposed filter segment to the left, counter-clockwise relative to the base segment, so as to keep a sufficient amount of the slots in superimposed overlying relation and allow passage of the threaded rods throughout the length of the well strainer. Once the well strainer is assembled with preselected gaps between adjacent filter segments, it is possible to adjust the filter spacing or gaps between filter segments by simply loosening the nuts at one end of the well strainer sufficiently to allow for relocation of the locator pins to different locator sockets in an adjacent filter segment. It is not necessary to totally disassemble the well strainer of the present invention in order to adjust the gap between adjacent filter segments.
With particular reference to FIG. 5 of the drawings, there is shown a portion of the filter segment 30 between adjacent arcuate slots whereat the upper and lower surfaces 36 and 38 are substantially smooth with the exception of a thin flat filtering surface 66 and 68 at the periphery of each of the upper and lower surfaces 36 and 38. The inner, circular surface 32 of the filter segment 30 is convex to enhance fluid flow through the well strainer. The inner, cylindrical surfaces 32 of each of the superimposed filter segments 30 defines a cylindrical inner cavity within the well strainer. As can be seen from the cross-section through the filter segment 30, the body of the segment is substantially wedge shaped in that it tapers down from a wider outer periphery at the outer surface 34 to a thin inner dimension near the inner surface 32. The substantially smooth upper and lower surfaces 36 and 38 facilitate fluid flow over the filter segment. Further, the downward taper of the upper surface 36 from the outside to the inside of the wedge segment facilitates the passage of any solid particles which may enter the well strainer to move from the outer surface 34 to the inner surface 32 and fall down within the inner cylindrical cavity of the well strainer. The smooth portion of the upper and lower surfaces 36 and 38 is maximized, that is the obstruction to these surfaces is minimized so as to maximize the effective filtering area of each filter segment 30 and, thereby, maximize the fluid extraction capacity of the well strainer.
As illustrated in FIG. 6 of the drawings, each of the locator sockets 52 is located within the flat filtering annulus 66 in the upper segment surface 36. Likewise, each of locator pins 62 and 64 projects downwardly from the flat filtering annulus 68 in the lower segment surface 38. The number of slots and associated adjustable gap elements on each filter segment is kept at a minimum so as to provide the least obstruction to fluid flow between filter segments and, thereby, maximize fluid extraction while at the same time providing the necessary stability and strength to the well strainer. For example, a three and three-quarter inch outer diameter well strainer having filter segments with three inch inner diameter openings and three and three-quarter inch outer diameter surfaces only requires the use of three circumferentially spaced threaded rod receiving slots, three pairs of wedge supports and wedge seats, and three sets of locator pins and sockets.
As illustrated in FIG. 3 of the drawings and in accordance with another embodiment of the present invention, an annular filter segment or ring is generally designated by the reference numeral 70 and shown to include cylindrical inner and outer surfaces 72 and 74 and upper and lower surfaces 76 and 78. A plurality of circumferentially spaced, arcuate, elongate slots 80 extend axially through filter segment 70 and are adapted for receiving elongate threaded rods which secure a stack of superimposed filter segments 70 into a well strainer. Extending from the upper surface 76 adjacent each of the arcuate slots 80 are pairs of radially spaced support wedges 82 and 84. In the periphery of upper surface 76 and adjacent the support wedges 84 are sets of six locator sockets 86 adapted to receive locator pins extending from the lower surface of an adjacent filter segment.
The filter segment 70 is similar to the filter segment 30 of FIGS. 2A and 2B except that filter segment 70 is larger in diameter and, therefore, adapted for use with five elongate threaded rods and is designed to only provide for three different angular positions of adjacent filter segments and for two different gaps between segments. Although it is not shown in the drawing, it is to be understood that five pairs of two locator pins project from the lower segment surface 78 opposite the second and fifth locator sockets 86 of each set of six sockets, counting sockets from right to left (counter-clockwise). Thus, the pairs of locator pins and the sets of six locator sockets 86 provide for a center, truly superimposed position, a second position rotating the segment clockwise, and a third position rotating the segment counter-clockwise.
Also, projecting from the lower surface 78 are pairs of radially spaced wedge seats and guide members adjacent each slot 80. Each of the support wedges 82 and 84 have convex upper surfaces like those of the support wedges 48 and 50 of filter segment 30 (FIG. 6). Each of the wedge seats of filter segment 70 have concave lower surfaces similar to those of the wedge seats 54 and 56 of filter segment 30 (FIG. 7). Again, the obstruction to the smooth upper and lower surfaces 76 and 78 of filter segment 70 is kept at a minimum, that is, keeping the number and length of slots 80, support wedges 82 and 86, and wedge seats to a minimum so as to maximize the fluid filtering capacity of a well strainer constructed of a plurality of superimposed filter segments 70.
As represented in FIG. 4 of the drawings, and in accordance with yet another embodiment of the present invention, an annular filter segment generally designated by the reference numeral 90 is shown to include cylindrical inner and outer surfaces 92 and 94 and upper and lower surfaces 96 and 98. Like filter segments 30 and 70, filter segment 90 includes a plurality of circumferentially spaced pairs of support wedges 100 and 102, projecting upwardly from the upper segment surface 96. Likewise, filter segment 90 includes circumferentially spaced pairs of wedge seats projecting from lower segment surface 98. Again, the upper surface of each of the support wedges is convex and the lower surface of each of the wedge seats is concave.
Filter segment 90 differs from filter segments 30 and 70 in that it does not include locator pins and sockets, but instead has a plurality of circumferentially spaced, elongate, arcuate, openings 104, each including a plurality of threaded rod receiving nodes or positions 106, 108, and 110, which serve to indicate the desired annular position of one filter segment relative to another. Each of the nodes 106, 108, and 110 is a substantially cylindrical opening and has a diameter slightly larger than the diameter of the threaded rod used to assemble the well strainer. Each of the nodes is connected with an adjacent node by an elongated, arcuate opening having a radial dimension slightly less than the diameter of the threaded rods. The filter segment 90 is constructed of a plastic material sufficiently resilient to allow the threaded rod to be inserted through a particular node, and then have the segment rotated relative to the rod to position the rod in another node. The annular filter segment 90 is designed to accommodate five elongated threaded rods, provides three angular positions between adjacent filter segments, and provides for two different filter spacings or gaps between adjacent segments. For example, with adjacent segments axially aligned with the rod receiving nodes, support wedges, and wedge seats of adjacent segments truly superimposed, a gap of 10/1000 of an inch is provided between the upper surface of one segment and the lower surface of the adjacent segment. By adjusting one segment relative to the other, either one position to the right or one position to the left, a gap of 20/1000 of an inch is provided between adjacent segments. Again, the adjustment made by either rotating the segment to the right or to the left of a central truly superimposed position provides for the same adjustment of gap between segments so that segments are alternately rotated right and then left to allow the threaded rods to extend the entire length of the well strainer.
Although the filter segments 70 and 90 of FIGS. 3 and 4 are shown to provide three different angular positions and two different filter gaps between adjacent filter segments, it is to be understood that a greater number of angular positions and filter gaps can be accommodated by either increasing the number of locator sockets 86 or reducing the number of pins in filter segment 70 and by increasing the number of threaded rod receiving nodes in filter segment 90.
A well strainer constructed of filter segments, in accordance with the present invention, provides for efficient fluid extraction in that the gap between adjacent filter segments can be adjusted to accommodate different well bore conditions and to extract different fluid types and viscosities, maximizes the filtering capacity by minimizing the obstruction to the upper and lower surfaces of each filter segment, and allows for selection of the gap between filter segments, not only during assembly of the well strainer but also following assembly by loosening one end of the well strainer and rotating adjacent filter segments one relative to the other. Additionally, each of the filter segments of the present invention provides an indication of the selected filtering gap by either locator pins and sockets or threaded rod receiving nodes which make it easier to construct the well strainer with the proper gap between adjacent filter segments.
Although the present invention as described above and shown in the drawings is directed to a bottom hole well strainer, it is to be understood that the well strainer of the present invention may be located at the bottom or anywhere along the length of a fluid extracting pipe, and that a plurality of well strainers may be used in combination along the length and at the bottom of a pipe for extracting fluid at a number of selected depths in a well hole.
Thus, it will be appreciated that as a result of the present invention, a highly effective improved well strainer is provided by which the principal objective, among others, is completely fulfilled. It is contemplated, and will be apparent to those skilled in the art from the preceding description and accompanying drawings, that modifications and/or changes may be made in the illustrated embodiments without departure from the present invention. Accordingly, it is expressly intended that the foregoing description and accompanying drawings are illustrative of preferred embodiments only, not limiting, and that the true spirit and scope of the present invention be determined by reference to the appended claims. | A well strainer is provided which includes a plurality of stacked, annular, filter segments with each segment including a plurality of elongate, arcuate, threaded rod receiving slots, ramped bearing surfaces near each slot, and position indicators in the vicinity of the ramped bearing surfaces and slots. The gap between adjacent annular filter segments is selected by rotating one segment relative to another to a desired position whereat indicator points are received within respective indicator sockets. Guide members adjacent the ramped bearing surfaces help to keep adjacent filter segments in true superimposed relation. Once the well strainer has been assembled by stacking each of the annular filter segments, one on top of the other in superimposed relation along a common longitudinal axis and securing the stack together by a plurality of threaded rods which extend along the length of the stack, adjustments in the gaps between adjacent filter segments can be made by simply loosening the nuts at one end of the stack to allow the indicator points of one segment to be lifted out of the indicator sockets of an adjacent segment and to relieve the bearing pressure between adjacent segments so that one segment can be rotated relative to another. There is no need to completely disassemble the well strainer in order to adjust the gap between adjacent filter segments. | 1 |
[0001] This application claims priority from U.S. Provisional Application 60/425,219 filed Nov. 8, 2002; the entire contents of which are hereby incorporated herein by reference.
[0002] This invention relates to methods of treating various central nervous system and other disorders by administering a compound that exhibits activity as an alpha2delta ligand (α2δ ligand). Such compounds have affinity for the α2δ subunit of a calcium channel. Such compounds have also been referred to in the literature as gamma-aminobutyric acid (GABA) analogs.
BACKGROUND OF THE INVENTION
[0003] Several alpha2delta ligands are known. Gabapentin, a cyclic alpha2delta ligand, is now commercially available (Neurontin®, Warner-Lambert Company) and extensively used clinically for treatment of epilepsy and neuropathic pain. Such cyclic alpha2delta ligands are described in U.S. Pat. No. 4,024,175, which issued on May 17, 1977, and U.S. Pat. No. 4,087,544, which issued on May 2, 1978. Other series of alpha2delta ligands are described in U.S. Pat. No. 5,563,175, which issued on Oct. 8, 1996, U.S. Pat. No. 6,316,638, which issued on Nov. 13, 2001, U.S. Provisional Patent Application 60/353,632, which was filed on Jan. 31, 2002, European Patent Application EP 1112253, which was published on Jul. 4, 2001, PCT Patent Application WO 99/08671, which was published on Feb. 25, 1999, and PCT Patent Application WO 99/61424, which was published on Dec. 2, 1999. These patents and applications are incorporated herein by reference in their entireties.
SUMMARY OF THE INVENTION
[0004] This invention relates to a method of treating a disorder or condition selected from faintness attacks, epilepsy, asphyxia, general anoxia, hypoxia, spinal cord trauma, traumatic brain injury, head trauma, cerebral ischemia, stroke (including thromboembolic stroke, focal ischemia, global ischemia, transient cerebral ishemia attacks and other cerebral vascular problems accompanied by cerebral ischemia such as in patients undergoing carotid endarterectomy or other vascular surgical procedures in general or diagnostic vascular surgical procedures such as angiography), cramp caused by thiosemicarbazide, cardiazole cramp, and cerebral vascular disorders due to acute or chronic cerebrovascular damage such as cerebral infarction, subarachnoid haemorrhage or cerebral oedema in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.
[0005] This invention also relates to a method of treating a disorder or condition selected from the group consisting of neurocardiac disorders such as neurocardiac syncope, neurogenic syncope, hypersensitive Carotid sinus, neurovascular syndrome and arrythmias including arrythmias secondary to gastrointestinal disturbances in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.
[0006] This invention also relates to a method of treating a disorder or condition selected from acute pain, chronic pain, pain resulting from soft tissue and peripheral damage such as acute trauma; postherpetic neuralgia, occipital neuralgia, trigeminal neuralgia, segmental or intercostal neuralgia and other neuralgias; pain associated with osteoarthritis and rheumatoid arthritis; musculo-skeletal pain such as pain associated with strains, sprains and trauma such as broken bones; spinal pain, central nervous system pain such as pain due to spinal cord or brain stem damage; lower back pain, sciatica, dental pain, myofascial pain syndromes, episiotomy pain, gout pain, and pain resulting from burns; deep and visceral pain, such as heart pain; muscle pain, eye pain, inflammatory pain, orofacial pain, for example, odontalgia; abdominal pain, and gynecological pain, for example, dysmenorrhoea, labour pain and pain associated with endometriosis; somatogenic pain; pain associated with nerve and root damage, such as pain associated with peripheral nerve disorders, for example, nerve entrapment and brachial plexus avulsions; pain associated with limb amputation, tic douloureux, neuroma, or vasculitis; diabetic neurapathy, chemotherapy-induced-neuropathy, acute herpetic and postherpetic neuralgia; atypical facial pain, neuropathic lower back pain, and arachnoiditis, trigeminal neuralgia, occipital neuralgia, segmental or intercostal neuralgia, HIV related neuralgias and AIDS related neuralgias and other neuralgias; allodynia, hyperalgesia, burn pain, idiopathic pain, pain caused by chemotherapy; occipital neuralgia, psychogenic pain, brachial plexus avulsion, pain associated with restless legs syndrome; pain associated with gallstones; pain caused by chronic alcoholism or hypothyroidism or uremia or vitamin deficiencies; neuropathic and non-neuropathic pain associated with carcinoma, often referred to as cancer pain, phantom limb pain, functional abdominal pain, headache, including migraine with aura, migraine without aura and other vascular headaches, acute or chronic tension headache, sinus headache and cluster headache; temperomandibular pain and maxillary sinus pain; pain resulting from ankylosing spondylitis; pain caused by increased bladder contractions; post operative pain, scar pain, and chronic non-neuropathic pain such as pain associated with HIV, anthralgia, vasculitis and fibromyalgia in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.
[0007] This invention also relates to a method of treating a disorder or condition selected from mood disorders, such as depression, or more particularly, depressive disorders, for example, major depressive disorder, severe unipolar recurrent major depressive episodes, dysthymic disorder, depressive neurosis and neurotic depression, melancholic depression including anorexia, weight loss, insomnia, early morning waking or psychomotor retardation, atypical depression (or reactive depression) including increased appetite, hypersomnia, psychomotor agitation or irritability; treatment resistant depression; seasonal affective disorder and pediatric depression; premenstrual syndrome, premenstrual dysphoric disorder, hot flashes, bipolar disorders or manic depression, for example, bipolar I disorder, bipolar II disorder and cyclothymic disorder; seasonal affective disorder, conduct disorder and disruptive behavior disorder; stress related somatic disorders and anxiety disorders, such as panic disorder with or without agoraphobia, agoraphobia without history of panic disorder, specific phobias (e.g., specific animal phobias), social anxiety disorder, social phobia, obsessive-compulsive disorder, stress disorders including post-traumatic stress disorder and acute stress disorder, and generalized anxiety disorder in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.
[0008] This invention also relates to a method of treating a disorder or condition selected from the group consisting of borderline personality disorder; schizophrenia and other psychotic disorders, for example, schizophreniform disorders, schizoaffective disorders, delusional disorders, brief psychotic disorders, shared psychotic disorders, psychotic disorders due to a general medical condition, psychotic disorders with delusions or hallucinations, substance induced psychotic disorder, psychotic episodes of anxiety, anxiety associated with psychosis, psychotic mood disorders such as severe major depressive disorder; mood disorders associated with psychotic disorders such as acute mania and depression associated with bipolar disorder, mood disorders associated with schizophrenia; and behavioral disturbances associated with mental retardation in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.
[0009] This invention also relates to a method of treating a disorder or condition selected from the group consisting of sleep disorders such as insomnia (e.g., primary insomnia including psychophysiological and idiopathic insomnia, secondary insomnia including insomnia secondary to restless legs syndrome, Parkinson's disease or another chronic disorder, and transient insomnia), somnambulism, sleep deprivation, REM sleep disorders, sleep apnea, hypersomnia, parasomnias, sleep-wake cycle disorders, jet lag, narcolepsy, sleep disorders associated with shift work or irregular work schedules, deficient sleep quality due to a decrease in slow wave sleep caused by medications or other sources, and other sleep disorders in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.
[0010] This invention also relates to a method of increasing slow wave sleep and increasing growth hormone secretion in a human subject comprising administering to a human subject in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.
[0011] This invention also relates to a method of treating a disorder or condition selected from the group consisting of respiratory diseases, particularly those associated with excess mucus secretion, such as chronic obstructive airways disease, bronchopneumonia, chronic bronchitis, cystic fibrosis, adult respiratory distress syndrome, and bronchospasm; cough, whooping cough, angiotensin converting enzyme (ACE) induced cough, pulmonary tuberculosis, allergies such as eczema and rhinitis; contact dermatitis, atopic dermatitis, urticaria, and other eczematoid dermatitis; itching, hemodialysis associated itching; inflammatory diseases such as inflammatory bowel disease, psoriasis, osteoarthritis, cartilage damage (e.g., cartilage damage resulting from physical activity or osteoarthritis), rheumatoid arthritis, psoriatic arthritis, asthma, pruritis and sunburn; and hypersensitivity disorders such as poison ivy in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.
[0012] This invention also relates to a method of treating a disorder or condition selected from the group consisting of neurodegenerative disorders, such as Parkinson's disease (PD), Huntington's disease (HD) and Alzheimer's disease (AD); delerium, dementias (e.g., senile dementia of the Alzheimer's type, senile dementia, vascular dementia, HIV-1 associated dementia, AIDS dementia complex (ADC), dementias due to head trauma, Parkinson's disease, Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease, or due to multiple etiologies), amnestic disorders, other cognitive or memory disorders, and behavioral symptoms of dementia in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.
[0013] This invention also relates to a method of treating a disorder or condition selected from the group consisting of Down's syndrome; Sjogren's syndrome, hypertension, hematopoiesis, postoperative neuroma, benign prostatic hypertrophy, periodontal disease, hemorrhoids and anal fissures, infertility, reflex sympathetic dystrophy, hepatitis, tenalgia attendant to hyperlipidemia, vasodilation, fibrosing and collagen diseases such as scleroderma and eosinophilic fascioliasis; and vasospastic diseases such as angina, migraine and Reynaud's disease in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.
[0014] This invention also relates to a method of treating a disorder or condition selected from the group consisting of ophthalmic diseases such as dry eye syndrome, conjunctivitis, vernal conjunctivitis, and the like; and ophthalmic conditions associated with cell proliferation such as proliferative vitreoretinopathy in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.
[0015] This invention also relates to a method of treating a disorder or condition selected from the group consisting of autism, attention deficit hyperactivity disorder (ADHD), angiogenesis (i.e., use for the inhibition of angiogenesis), Reiter's syndrome and anthropathies in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.
[0016] This invention also relates to a method of treating a disorder or condition selected from the group consisting of substance-related disorders arising from the use of alcohol, amphetamines (or amphetamine-like substances) caffeine, cannabis, cocaine, hallucinogens, inhalants and aerosol propellants, nicotine, opioids, phenylglycidine derivatives, sedatives, hypnotics, and anxiolytics, which substance-related disorders include dependence and abuse, intoxication, withdrawal, intoxication delerium and withdrawal delerium; and addiction disorders involving addictions to behaviors (e.g., addictions to gambling and other addictive behaviors) in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.
[0017] This invention also relates to a method of treating a disorder or condition selected from the group consisting of Down's syndrome; demyelinating diseases such as multiple sclerosis (MS) and amylolateral sclerosis (ALS) in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.
[0018] This invention also relates to a method of treating a disorder or condition selected from the group consisting of pervasive development disorder, fibromyalgia, human immunodeficiency virus (HIV) infections; HIV encephalopathy; dissociative disorders such as body dysmorphic disorders; eating disorder such as anorexia and bulimia; ulcerative colitis; Crohn's disease; irritable bowel syndrome; chronic pancreatitis, chronic fatigue syndrome; sudden infant death syndrome (SIDS); overactive bladder; lower urinary tract symptoms of overactive bladder; chronic cystitis; chemotherapy induced cystitis; cough, angiotensin converting enzyme (ACE) induced cough, itch, hiccups, premenstrual syndrome, premenstrual dysphoric disorder, amenorrheic disorders such as desmenorrhea; reflex sympathetic dystrophy such as shoulder/hand syndrome; plasma extravasation resulting from cytokine chemotherapy; disorders of bladder function such as chronic cystitis, bladder detrusor hyper-reflexia, inflammation of the urinary tract and urinary incontinence, including urinary urge incontinence, overactive bladder, stress incontinence and mixed incontinence; fibrosing and collagen diseases such as scleroderma and eosinophilic fascioliasis; blood flow disorders caused by vasodilation and vasospastic diseases such as angina and Reynaud's disease; sexual dysfunctions including premature ejaculation and male erectile dysfunction in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.
[0019] This invention also relates to a method of treating a disorder or condition selected from the group consisting of movement disorders such as primary movement disorders, akinesias, dyskinesias (e.g., familial paroxysmal dyskinesia, tardive dyskinesia, tremor, chorea, myoclonus, tics and other dyskinesias) spasticities, Tourette's syndrome, Scott syndrome, palsys (e.g., Bell's palsy, cerebral palsy, birth palsy, brachial palsy, wasting palsy, ischemic palsy, progressive bulbar palsy and other palsys), akinetic-rigid syndrome; extra-pyramidal movement disorders such as medication-induced movement disorders, for example, neuroleptic-induced Parkinsonism, neuroleptic malignant syndrome, neuroleptic-induced acute dystonia, neuroleptic-induced acute akathisia, neuroleptic-induced tardive dyskinesia and medication-induced postural tremour; restless legs syndrome and movement disorders associated with Parkinson's disease or Huntington's disease in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.
[0020] This invention also relates to a method of treating a disorder or condition selected from the group consisting of mastalgia syndromes, motion sickness, systemic lupus erythematosis and immune dysfunctions (e.g., stress induced immune dysfunctions such as idiopathic immune dysfunctions, post infection immune dysfunctions, post lumpectomy immune dysfunctions, porcine stress syndrome, bovine shipping fever, equine paroxysmal fibrillation, confinement dysfunction in chicken, sheering stress in sheep, and human-animal interaction stress in dogs) in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.
[0021] This invention also relates to a method of treating a disorder or condition selected from the group consisting of gastrointestinal (GI) disorders, including inflammatory gastrointestinal disorders such as inflammation bowel disease, disorders caused by helicobacter pylon and diseases of the GI tract such as gastritis, proctitis, gastroduodenal ulcers, peptic ulcers, dyspepsia, disorders associated with the neuronal control of viscera, ulcerative colitis, Crohn's disease, irritable bowel syndrome and emesis, including post operative nausea and post operative vomiting, and including acute, delayed or anticipatory emesis (emesis includes emesis induced by chemotherapy, radiation, toxins, viral or bacterial infections, pregnancy, vestibular disorders, for example, motion sickness, vertigo, dizziness and Meniere's disease, surgery, migraine, variations in intercranial pressure, gastro-oesophageal reflux disease, acid indigestion, over indulgence in food or drink, acid stomach, waterbrash or regurgitation, heartburn, for example, episodic, nocturnal or meal-induced heartburn, and dyspepsia) in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.
[0022] This invention also relates to a method of treating a disorder or condition selected from the group consisting of neoplasms, including breast tumours, gastric carcinomas, gastric lymphomas, neuroganglioblastomas and small cell carcinomas such as small cell lung cancer in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.
[0023] The foregoing methods are also referred to herein, collectively, as the “invention methods”.
[0024] Preferred embodiments of the invention methods utilize an alpha2delta ligand that is a cyclic amino acid compound of Formula I
wherein R 1 is hydrogen or lower alkyl and n is an integer of from 4 to 6, and the pharmaceutically acceptable salts thereof. An especially preferred embodiment utilizes a compound of Formula I where R 1 is hydrogen and n is 5, which compound is 1-(aminomethyl)-cyclohexane acetic acid, known generically as gabapentin. Other preferred alpha2delta ligands, or a pharmaceutically acceptable salt thereof, are compounds of Formula I wherein the cyclic ring is substituted, for example with alkyl such as methyl or ethyl. Typical of such compounds include (1-aminomethyl-3-methylcyclohexyl)acetic acid, (1-aminomethyl-3-methylcyclopentyl)acetic acid, and (1-aminomethyl-3,4-dimethylcyclopentyl)acetic acid.
[0025] The cyclic amino acids of Formula I and methods of synthesizing them are described in U.S. Pat. No. 4,024,175 and U.S. Pat. No. 4,087,544, which are both incorporated herein by reference in their entireties.
[0026] In other preferred embodiments, the invention methods utilize an alpha2delta ligand of Formula II
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is a straight or branched unsubstituted alkyl of from 1 to 6 carbon atoms, unsubstituted phenyl, or unsubstituted cycloalkyl of from 3 to 6 carbon atoms; R 2 is hydrogen or methyl; and R 3 is hydrogen, methyl, or carboxyl.
[0030] Diastereomers and enantiomers of compounds of Formula II can be utilized in the invention methods.
[0031] Preferred embodiments of the invention methods utilize a compound of Formula II that is 3-aminomethyl-5-methyl-hexanoic acid or, especially, (S)-3-(aminomethyl)-5-methyl-hexanoic acid, which is known generically as pregabalin.
[0032] Other preferred embodiments of the invention methods utilize a compound of Formula II that is 3-(1-aminoethyl)-5-methylheptanoic acid or 3-(1-aminoethyl)-5-methylhexanoic acid.
[0033] Alpha2delta ligands having the Formula II, and the synthesis of such compounds, are described in U.S. Pat. No. 5,563,175, which is incorporated herein by reference in its entirety.
[0034] Other preferred embodiments of the invention methods utilize an alpha2delta ligand that is a compound of the Formula III, IIIC, IIIF, IIIG, or IIIH
or a pharmaceutically acceptable salt thereof wherein:
n is an integer of from 0 to 2; m is an integer of from 0 to 3; R is sulfonamide,
amide, phosphonic acid, heterocycle, sulfonic acid, or hydroxamic acid; with the proviso that R can not be sulfonic acid when m is 2 and n is 1;
R 1 to R 14 are each independently selected from hydrogen or straight or branched alkyl of from 1 to 6 carbons, unsubstituted or substituted benzyl or phenyl which substituents are selected from halogen, alkyl, alkoxy, hydroxy, carboxy, carboalkoxy, trifluoromethyl, and nitro; A′ is a bridged ring selected from
wherein is the point of attachment; Z 1 to Z 4 are each independently selected from hydrogen and methyl; o is an integer of from 1 to 4; and p is an integer of from 0 to 2.
[0051] Other preferred embodiments of the invention methods utilize a compound selected from the following compounds of the Formula III, IIIC, IIIF, IIIG, or IIIH and their pharmaceutically acceptable salts:
[0052] (1-Aminomethyl-cyclohexylmethyl)-phosphonic acid;
[0053] (1R-trans)(1-Aminomethyl-3-methyl-cyclohexylmethyl)-phosphonic acid;
[0054] (trans)(1-Aminomethyl-3,4-dimethyl-cyclopentylmethyl)-phosphonic acid;
[0055] (1R-trans)(1-Aminomethyl-3-methyl-cyclopentylmethyl)-phosphonic acid;
[0056] (1S-cis)(1-Aminomethyl-3-methyl-cyclopentylmethyl)-phosphonic acid;
[0057] (1S-trans)(1-Aminomethyl-3-methyl-cyclopentylmethyl)-phosphonic acid;
[0058] (1R-cis)(1-Aminomethyl-3-methyl-cyclopentylmethyl)-phosphonic acid;
[0059] (1α,3α,4α)(1-Aminomethyl-3,4-dimethyl-cyclopentylmethyl)-phosphonic acid;
[0060] (1α,3β,4β)(1-Aminomethyl-3,4-dimethyl-cyclopentylmethyl)-phosphonic acid;
[0061] (R)(1-Aminomethyl-3,3-dimethyl-cyclopentylmethyl)-phosphonic acid;
[0062] (S)(1-Aminomethyl-3,3-dimethyl-cyclopentylmethyl)-phosphonic acid;
[0063] (1-Aminomethyl-3,3-dimethyl-cyclobutylmethyl)-phosphonic acid;
[0064] 2-(1-Aminomethyl-cyclohexyl)-N-hydroxy-acetamide;
[0065] (1S-trans)2-(1-Aminomethyl-3-methyl-cyclohexyl)-N-hydroxy-acetamide;
[0066] (trans)2-(1-Aminomethyl-3,4-dimethyl-cyclopentyl)-N-hydroxy-acetamide;
[0067] (1S-cis)2-(1-Aminomethyl-3-methyl-cyclopentyl)-N-hydroxy-acetamide;
[0068] (1R-trans)2-(1-Aminomethyl-3-methyl-cyclopentyl)-N-hydroxy-acetamide;
[0069] (1R-cis)2-(1-Aminomethyl-3-methyl-cyclopentyl)-N-hydroxy-acetamide;
[0070] (1S-trans)2-(1-Aminomethyl-3-methyl-cyclopentyl)-N-hydroxy-acetamide;
[0071] (1α,3α,4α)2-(1-Aminomethyl-3,4-dimethyl-cyclopentyl)-N-hydroxy-acetamide;
[0072] (1α,3β,4β)2-(1-Aminomethyl-3,4-dimethyl-cyclopentyl)-N-hydroxy-acetamide;
[0073] (S)2-(1-Aminomethyl-3,3-dimethyl-cyclopentyl)-N-hydroxy-acetamide;
[0074] (R)2-(1-Aminomethyl-3,3-dimethyl-cyclopentyl)-N-hydroxy-acetamide;
[0075] 2-(1-Aminomethyl-3,3-dimethyl-cyclobutyl)-N-hydroxy-acetamide;
[0076] N-[2-(1-Aminomethyl-cyclohexyl)-ethyl]-methanesulfonamide;
[0077] (1S-cis)N-[2-(1-Aminomethyl-3-methyl-cyclohexyl)-ethyl]-methanesulfonamide;
[0078] (trans)N-[2-(1-Aminomethyl-3,4-dimethyl-cyclopentyl)-ethyl]-methanesulfonamide;
[0079] (1S-cis)N-[2-(1-Aminomethyl-3-methyl-cyclopentyl)-ethyl]-methanesulfonamide;
[0080] (1R-trans)N-[2-(1-Aminomethyl-3-methyl-cyclopentyl )-ethyl]-methanesulfonamide;
[0081] (1R-cis)N-[2-(1-Aminomethyl-3-methyl-cyclopentyl)-ethyl]-methanesulfonamide;
[0082] (1S-cis)N-[2-(1-Aminomethyl-3-methyl-cyclopentyl)-ethyl]-methanesulfonamide;
[0083] (1α,3α,4α)N-[2-(1-Aminomethyl-3,4-dimethyl-cyclopentyl)-ethyl]-methanesulfonamide;
[0084] (1α,3β,4β)N-[2-(1-Aminomethyl-3,4-dimethyl-cyclopentyl)-ethyl]-methanesulfonamide;
[0085] (S)N-[2-(1-Aminomethyl-3,3-dimethyl-cyclopentyl)-ethyl]-methanesulfonamide;
[0086] (R)N-[2-(1-Aminomethyl-3,3-dimethyl-cyclopentyl)-ethyl]-methanesulfonamide;
[0087] N-[2-(1-Aminomethyl-3,3-dimethyl-cyclobutyl)-ethyl]-methanesulfonamide;
[0088] (1S-cis)3-(1-Aminomethyl-3-methyl-cyclohexylmethyl )-4H-[1,2,4]oxadiazol-5-one;
[0089] (trans)3-(1-Aminomethyl-3,4-dimethyl-cyclopentylmethyl)-4H-[1,2,4]oxadiazol-5-one;
[0090] (1S-cis)3-(1-Aminomethyl-3-methyl-cyclopentylmethyl)-4H-[1,2,4]oxadiazol-5-one;
[0091] (1R-trans)3-(1-Aminomethyl-3-methyl-cyclopentylmethyl )-4H-[1,2,4]oxadiazol-5-one;
[0092] (1R-cis)3-(1-Aminomethyl-3-methyl-cyclopentylmethyl)-4H-[1,2,4]oxadiazol-5-one;
[0093] (1S-trans)3-(1-Aminomethyl-3-methyl-cyclopentylmethyl )-4H-[1,2,4]oxadiazol-5-one;
[0094] (1α,3α,4α)3-(1-Aminomethyl-3,4-dimethyl-cyclopentylmethyl)-4H-[1,2,4]oxadiazol-5-one;
[0095] (1α,3β,4β)3-(1-Aminomethyl-3,4-dimethyl-cyclopentylmethyl)-4H-[1,2,4]oxadiazol-5-one;
[0096] (S)3-(1-Aminomethyl-3,3-dimethyl-cyclopentylmethyl )-4H-[1,2,4]oxadiazol-5-one;
[0097] (R)3-(1-Aminomethyl-3,3-dimethyl-cyclopentylmethyl)-4H-[1,2,4]oxadiazol-5-one;
[0098] 3-(1-Aminomethyl-3,3-dimethyl-cyclobutylmethyl)-4H-[1,2,4]oxadiazol-5-one;
[0099] 3-(1-Aminomethyl-cyclohexylmethyl)-4H-[1,2,4]oxadiazole-5-thione;
[0100] (1S-cis)3-(1-Aminomethyl-3-methyl-cyclohexylmethyl )-4H-[1,2,4]oxadiazole-5-thione;
[0101] (trans)3-(1-Aminomethyl-3,4-dimethyl-cyclopentyl methyl)-4H-[1,2,4]oxadiazole-5-thione;
[0102] (1S-cis)3-(1-Aminomethyl-3-methyl-cyclopentylmethyl)-4H-[1,2,4]oxadiazole-5-thione;
[0103] (1R-trans)3-(1-Aminomethyl-3-methyl-cyclopentylmethyl )-4H-[1,2,4]oxadiazole-5-thione;
[0104] (1R-cis)3-(1-Aminomethyl-3-methyl-cyclopentylmethyl)-4H-[1,2,4]oxadiazole-5-thione;
[0105] (1S-trans)3-(1-Aminomethyl-3-methyl-cyclopentylmethyl )-4H-[1,2,4]oxadiazole-5-thione;
[0106] (1α,3α,4α)3-(1-Aminomethyl-3,4-dimethyl-cyclopentylmethyl)-4H-[1,2,4]oxadiazole-5-thione;
[0107] (1α,3β,4β)3-(1-Aminomethyl-3,4-dimethyl-cyclopentylmethyl)-4H-[1,2,4]oxadiazole-5-thione;
[0108] (S)3-(1-Aminomethyl-3,3-dimethyl-cyclopentylmethyl)-4H-[1,2,4]oxadiazole-5-thione;
[0109] (R)3-(1-Aminomethyl-3,3-dimethyl-cyclopentylmethyl)-4H-[1,2,4]oxadiazole-5-thione;
[0110] 3-(1-Aminomethyl-3,3-dimethyl-cyclobutylmethyl)-4H-[1,2,4]oxadiazole-5-thione;
[0111] C-[1-(1H-Tetrazol-5-ylmethyl)-cyclohexyl]-methylamine;
[0112] (1S-cis)C-[3-Methyl-1-(1H-tetrazol-5-ylmethyl)-cyclohexyl]-methylamine;
[0113] (trans)C-[3,4-Dimethyl-1-(1H-tetrazol-5-ylmethyl )-cyclopentyl]-methylamine;
[0114] (1S-cis)C-[3-Methyl-1-(1H-tetrazol-5-ylmethyl)-cyclopentyl]-methylamine;
[0115] (1R-trans)C-[3-Methyl-1-(1H-tetrazol-5-ylmethyl )-cyclopentyl]-methylamine;
[0116] (1R-cis)C-[3-Methyl-1-(1H-tetrazol-5-yl methyl)-cyclopentyl]-methylamine;
[0117] (1S-trans)C-[3-Methyl-1-(1H-tetrazol-5-ylmethyl)-cyclopentyl]-methylamine;
[0118] (1α,3α,4α)C-[3,4-Dimethyl-1-(1H-tetrazol-5-ylmethyl)-cyclopentyl]-methylamine;
[0119] (1α,3β,4β)C-[3,4-Dimethyl-1-(1H-tetrazol-5-ylmethyl)-cyclopentyl]-methylamine;
[0120] (S)C-[3,3-Dimethyl-1-(1H-tetrazol-5-ylmethyl)-cyclopentyl]-methylamine;
[0121] (R)C-[3,3-Dimethyl-1-(1H-tetrazol-5-ylmethyl)-cyclopentyl]-methylamine;
[0122] C-[3,3-Dimethyl-1-(1H-tetrazol-5-ylmethyl)-cyclobutyl]-methylamine;
[0123] N-[2-(1-Aminomethyl-cyclohexyl)-ethyl]-C,C,C-trifluoro-methanesulfonamide;
[0124] (1S-cis)N-[2-(1-Aminomethyl-3-methyl-cyclohexyl )-ethyl]-C,C,C-trifluoro-methanesulfonamide;
[0125] (trans)N-[2-(1-Aminomethyl-3,4-dimethyl-cyclopentyl)-ethyl]-C,C,C-trifluoro-methanesulfonamide;
[0126] (1R-cis)N-[2-(1-Aminomethyl-3-methyl-cyclopentyl)-ethyl]-C,C,C-trifluoro-methanesulfonamide;
[0127] (1S-trans)N-[2-(1-Aminomethyl-3-methyl-cyclopentyl )-ethyl]-C,C,C-trifluoro-methanesulfonamide;
[0128] (1S-cis)N-[2-(1-Aminomethyl-3-methyl-cyclopentyl)-ethyl]-C,C,C-trifluoro-methanesulfonamide;
[0129] (1R-trans)N-[2-(1-Aminomethyl-3-methyl-cyclopentyl)-ethyl]-C,C,C-trifluoro-methanesulfonamide;
[0130] (1α,3α,4α)N-[2-(1-Aminomethyl-3,4-dimethyl-cyclopentyl)-ethyl]-C,C,C-trifluoro-methanesulfonamide;
[0131] (1α,3β,4β)N-[2-(1-Aminomethyl-3,4-dimethyl-cyclopentyl)-ethyl]-C,C,C-trifluoro-methanesulfonamide;
[0132] (S)N-[2-(1-Aminomethyl-3,3-dimethyl-cyclopentyl)-ethyl]-C,C,C-trifluoro-methanesulfonamide;
[0133] (R)N-[2-(1-Aminomethyl-3,3-dimethyl-cyclopentyl)-ethyl]-C,C,C-trifluoro-methanesulfonamide;
[0134] N-[2-(1-Aminomethyl-3,3-dimethyl-cyclobutyl)-ethyl]-C,C,C-trifluoro-methanesulfonamide;
[0135] 3-(1-Aminomethyl-cyclohexylmethyl)-4H-[1,2,4]thiadiazol-5-one;
[0136] (1S-cis)3-(1-Aminomethyl-3-methyl-cyclohexylmethyl)-4H-[1,2,4]thiadiazol-5-one;
[0137] (trans)3-(1-Aminomethyl-3,4-dimethyl-cyclopentylmethyl)-4H-[1,2,4]thiadiazol-5-one;
[0138] (1R-cis)3-(1-Aminomethyl-3-methyl-cyclopentylmethyl)-4H-[1,2,4]thiadiazol-5-one;
[0139] (1S-trans)3-(1-Aminomethyl-3-methyl-cyclopentylmethyl )-4H-[1,2,4]thiadiazol-5-one;
[0140] (1S-cis)3-(1-Aminomethyl-3-methyl-cyclopentylmethyl)-4H-[1,2,4]thiadiazol-5-one;
[0141] (1R-trans)3-(1-Aminomethyl-3-methyl-cyclopentylmethyl )-4H-[1,2,4]thiadiazol-5-one;
[0142] (1α,3α,4α)3-(1-Aminomethyl-3,4-dimethyl-cyclopentylmethyl)-4H-[1,2,4]thiadiazol-5-one;
[0143] (1α,3β,4β)3-(1-Aminomethyl-3,4-dimethyl-cyclopentylmethyl)-4H-[1,2,4]thiadiazol-5-one;
[0144] (S)3-(1-Aminomethyl-3,3-dimethyl-cyclopentylmethyl)-4H-[1,2,4]thiadiazol-5-one;
[0145] (R)3-(1-Aminomethyl-3,3-dimethyl-cyclopentylmethyl)-4H-[1,2,4]thiadiazol-5-one;
[0146] 3-(1-Aminomethyl-3,3-dimethyl-cyclobutylmethyl)-4H-[1,2,4]thiadiazol-5-one;
[0147] C-[1-(2-Oxo-2,3-dihydro-2λ 4- [1,2,3,5]oxathiadiazol-4-ylmethyl)-cyclohexyl]-methylamine;
[0148] (1S-cis)C-[3-Methyl-1-(2-oxo-2,3-dihydro-2λ 4- [1,2,3,5]oxathiadiazol-4-ylmethyl)-cyclohexyl]-methylamine;
[0149] (trans)C-[3,4-Dimethyl-1-(2-oxo-2,3-dihydro-2λ 4- [1,2,3,5]oxathiadiazol-4-ylmethyl)-cyclopentyl]-methylamine;
[0150] (1S-cis)C-[3-Methyl-1-(2-oxo-2,3-dihydro-2λ 4- [1,2,3,5]oxathiadiazol-4-ylmethyl)-cyclopentyl]-methylamine;
[0151] (1R-trans)C-[3-Methyl-1-(2-oxo-2,3-dihydro-2λ 4- [1,2,3,5]oxathiadiazol-4-ylmethyl)-cyclopentyl]-methylamine;
[0152] (1R-cis)C-[3-Methyl-1-(2-oxo-2,3-dihydro-2λ 4- [1,2,3,5]oxathiadiazol-4-ylmethyl)-cyclopentyl]-methylamine;
[0153] (1S-trans)C-[3-Methyl-1-(2-oxo-2,3-dihydro-2λ 4- [1,2,3,5]oxathiadiazol-4-ylmethyl)-cyclopentyl]-methylamine;
[0154] (1α,3α,4α)C-[3,4-Dimethyl-1-(2-oxo-2,3-dihydro-2λ 4- [1,2,3,5]oxathiadiazol-4-ylmethyl)-cyclopentyl]-methylamine;
[0155] (1α,3β,4β)C-[3,4-Dimethyl-1-(2-oxo-2,3-dihydro-2λ 4- [1,2,3,5]oxathiadiazol-4-ylmethyl)-cyclopentyl]-methylamine;
[0156] (S)C-[3,3-Dimethyl-1-(2-oxo-2,3-dihydro-2λ 4- [1,2,3,5]oxathiadiazol-4-ylmethyl)-cyclopentyl]-methylamine;
[0157] (R)C-[3,3-Dimethyl-1-(2-oxo-2,3-dihydro-2λ 4- [1,2,3,5]oxathiadiazol-4-ylmethyl)-cyclopentyl]-methylamine;
[0158] C-[3,3-Dimethyl-1-(2-oxo-2,3-dihydro-2λ 4- [1,2,3,5]oxathiadiazol-4-ylmethyl)-cyclobutyl]-methylamine;
[0159] (1-Aminomethyl-cyclohexyl)-methanesulfonamide;
[0160] (1R-trans)(1-Aminomethyl-3-methyl-cyclohexyl)-methanesulfonamide;
[0161] (trans)(1-Aminomethyl-3,4-dimethyl-cyclopentyl)-methanesulfonamide;
[0162] (1S-trans)(1-Aminomethyl-3-methyl-cyclopentyl)-methanesulfonamide;
[0163] (1R-cis)(1-Aminomethyl-3-methyl-cyclopentyl)-methanesulfonamide;
[0164] (1R-trans)(1-Aminomethyl-3-methyl-cyclopentyl)-methanesulfonamide;
[0165] (1S-cis)(1-Aminomethyl-3-methyl-cyclopentyl)-methanesulfonamide;
[0166] (1α,3β,4β)(1-Aminomethyl-3,4-dimethyl-cyclopentyl)-methanesulfonamide;
[0167] (1α,3α,4α)(1-Aminomethyl-3,4-dimethyl-cyclopentyl)-methanesulfonamide;
[0168] (R)(1-Aminomethyl-3,3-dimethyl-cyclopentyl)-methanesulfonamide;
[0169] (S)(1-Aminomethyl-3,3-dimethyl-cyclopentyl)-methanesulfonamide;
[0170] (1-Aminomethyl-3,3-dimethyl-cyclobutyl)-methanesulfonamide;
[0171] (1-Aminomethyl-cyclohexyl)-methanesulfonic acid;
[0172] (1R-trans)(1-Aminomethyl-3-methyl-cyclohexyl)-methanesulfonic acid;
[0173] (trans)(1-Aminomethyl-3,4-dimethyl-cyclopentyl)-methanesulfonic acid;
[0174] (1S-trans)(1-Aminomethyl-3-methyl-cyclopentyl)-methanesulfonic acid;
[0175] (1S-cis)(1-Aminomethyl-3-methyl-cyclopentyl)-methanesulfonic acid;
[0176] (1R-trans)(1-Aminomethyl-3-methyl-cyclopentyl)-methanesulfonic acid;
[0177] (1R-cis)(1-Aminomethyl-3-methyl-cyclopentyl)-methanesulfonic acid;
[0178] (1α,3β,4β)(1-Aminomethyl-3,4-dimethyl-cyclopentyl)-methanesulfonic acid;
[0179] (1α,3α,4α)(1-Aminomethyl-3,4-dimethyl-cyclopentyl)-methanesulfonic acid;
[0180] (R)(1-Aminomethyl-3,3-dimethyl-cyclopentyl)-methanesulfonic acid;
[0181] (S)(1-Aminomethyl-3,3-dimethyl-cyclopentyl)-methanesulfonic acid;
[0182] (1-Aminomethyl-3,3-dimethyl-cyclobutyl)-methanesulfonic acid;
[0183] (1-Aminomethyl-cyclopentylmethyl)-phosphonic acid;
[0184] 2-(1-Aminomethyl-cyclopentyl)-N-hydroxy-acetamide;
[0185] N-[2-(1-Aminomethyl-cyclopentyl)-ethyl]-methanesulfonamide;
[0186] 3-(1-Aminomethyl-cyclopentylmethyl)-4H-[1,2,4]oxadiazol-5-one;
[0187] 3-(1-Aminomethyl-cyclopentylmethyl)-4H-[1,2,4]oxadiazole-5-thione;
[0188] C-[1-(1H-Tetrazol-5-ylmethyl )-cyclopentyl]-methylamine;
[0189] N-[2-(1-Aminomethyl-cyclopentyl)-ethyl]-C,C,C-trifluoro-methanesulfonamide;
[0190] 3-(1-Aminomethyl-cyclopentylmethyl)-4H-[1,2,4]thiadiazol-5-one;
[0191] C-[1-(2-Oxo-2,3-dihydro-2λ 4- [1,2,3,5]oxathiadiazol-4-ylmethyl)-cyclopentyl]-methylamine;
[0192] (1-Aminomethyl-cyclopentyl)-methanesulfonamide;
[0193] (1-Aminomethyl-cyclopentyl)-methanesulfonic acid;
[0194] (9-Aminomethyl-bicyclo[3.3.1]non-9-ylmethyl)-phosphonic acid;
[0195] 2-(9-Aminomethyl-bicyclo[3.3.1]non-9-yl)-N-hydroxy-acetamide;
[0196] N-[2-(9-Aminomethyl-bicyclo[3.3.1]non-9-yl)-ethyl]-methanesulfonamide;
[0197] 3-(9-Aminomethyl-bicyclo[3.3.1]non-9-ylmethyl)-4H-[1,2,4]oxadiazol-5-one;
[0198] 3-(9-Aminomethyl-bicyclo[3.3.1]non-9-ylmethyl)-4H-[1,2,4]oxadiazole-5-thione;
[0199] C-[9-(1H-Tetrazol-5-ylmethyl)-bicyclo[3.3.1]non-9-yl]-methylamine;
[0200] N-[2-(9-Aminomethyl-bicyclo[3.3.1]non-9-yl)-ethyl]-C,C,C-trifluoro-methanesulfonamide;
[0201] 3-(9-Aminomethyl-bicyclo[3.3.1]non-9-ylmethyl)-4H-[1,2,4]thiadiazol-5-one;
[0202] C-[9-(2-Oxo-2,3-dihydro-2λ 4- [1,2,3,5]oxathiadiazol-4-ylmethyl)-bicyclo[3.3.1]non-9-yl]-methylamine;
[0203] (9-Aminomethyl-bicyclo[3.3.1]non-9-yl)-methanesulfonamide;
[0204] (9-Aminomethyl-bicyclo[3.3.1]non-9-yl)-methanesulfonic acid;
[0205] (2-Aminomethyl-adamantan-2-ylmethyl)-phosphonic acid;
[0206] 2-(2-Aminomethyl-adamantan-2-yl)-N-hydroxy-acetamide;
[0207] N-[2-(2-Aminomethyl-adamantan-2-yl)-ethyl]-methanesulfonamide;
[0208] 3-(2-Aminomethyl-adamantan-2-ylmethyl)-4H-[1,2,4]oxadiazol-5-one;
[0209] 3-(2-Aminomethyl-adamantan-2-ylmethyl)-4H-[1,2,4]oxadiazole-5-thione;
[0210] C-[2-(1H-Tetrazol-5-yl methyl)-adamantan-2-yl]-methylamine;
[0211] N-[2-(2-Aminomethyl-adamantan-2-yl )-ethyl]-C,C,C-trifluoro-methanesulfonamide;
[0212] 3-(2-Aminomethyl-adamantan-2-ylmethyl)-4H-[1,2,4]thiadiazol-5-one;
[0213] C-[2-(2-Oxo-2,3-dihydro-2λ 4- [1,2,3,5]oxathiadiazol-4-ylmethyl)-adamantan-2-yl]-methylamine;
[0214] (2-Aminomethyl-adamantan-2-yl)-methanesulfonamide;
[0215] (2-Aminomethyl-adamantan-2-yl)-methanesulfonic acid;
[0216] (1-Aminomethyl-cycloheptylmethyl)-phosphonic acid;
[0217] 2-(1-Aminomethyl-cycloheptyl)-N-hydroxy-acetamide;
[0218] N-[2-(1-Aminomethyl-cycloheptyl)-ethyl]-methanesulfonamide;
[0219] 3-(1-Aminomethyl-cycloheptylmethyl)-4H-[1,2,4]oxadiazole-5-thione;
[0220] N-[2-(1-Aminomethyl-cycloheptyl)-ethyl]-C,C,C-trifluoro-methanesulfonamide;
[0221] C-[1-(2-Oxo-2,3-dihydro-2I4-[1,2,3,5]oxathiadiazol-4-ylmethyl)-cycloheptyl]-methylamine;
[0222] (1-Aminomethyl-cycloheptyl)-methanesulfonamide;
[0223] (1-Aminomethyl-cycloheptyl)-methanesulfonic acid;
[0224] (1α,3α,4α)-(1-Aminomethyl-3,4-dimethyl-cyclopentyl)-acetic acid;
[0225] (1α,3α,4α)-(1-Aminomethyl-3,4-diethyl-cyclopentyl)-acetic acid;
[0226] (1α,3α,4α)-(1-Aminomethyl-3,4-diisopropyl-cyclopentyl)-acetic acid;
[0227] [1S-(1α,3α,4α)]-(1-Aminomethyl-3-ethyl-4-methyl-cyclopentyl)-acetic acid;
[0228] [1R-(1α,3α,4α)]-(1-Aminomethyl-3-ethyl-4-methyl-cyclopentyl)-acetic acid;
[0229] [1S-(1α,3α,4α)]-(1-Aminomethyl-3-isopropyl-4-methyl-cyclopentyl)-acetic acid;
[0230] [1R-(1α,3α,4α)]-(1-Aminomethyl-3-isopropyl-4-methyl-cyclopentyl)-acetic acid;
[0231] [1S-(1α,3α,4α)]-(1-Aminomethyl-3-ethyl-4-isopropyl-cyclopentyl)-acetic acid;
[0232] [1R-(1α,3α,4α)]-(1-Aminomethyl-3-ethyl-4-isopropyl-cyclopentyl)-acetic acid;
[0233] [1S-(1α,3α,4α)]-(1-Aminomethyl-3-tert-butyl-4-methyl-cyclopentyl)-acetic acid;
[0234] [1R-(1α,3α,4α)]-(1-Aminomethyl-3-tert-butyl-4-methyl-cyclopentyl)-acetic acid;
[0235] [1S-(1α,3α,4α)]-(1-Aminomethyl-3-tert-butyl-4-ethyl-cyclopentyl)-acetic acid;
[0236] [1R-(1α,3α,4α)]-(1-Aminomethyl-3-tert-butyl-4-ethyl-cyclopentyl)-acetic acid;
[0237] [1S-(1α,3α,4α)]-(1-Aminomethyl-3-tert-butyl-4-isopropyl-cyclopentyl)-acetic acid;
[0238] [1R-(1α,3α,4α)]-(1-Aminomethyl-3-tert-butyl-4-isopropyl-cyclopentyl)-acetic acid;
[0239] (1α,3α,4α)]-(1-Aminomethyl-3,4-di-tert-butyl-cyclopentyl)-acetic acid;
[0240] [1S-(1α,3α,4α)]-(1-Aminomethyl-3-methyl-4-phenyl-cyclopentyl)-acetic acid;
[0241] [1R-(1α,3α,4α)]-(1-Aminomethyl-3-methyl-4-phenyl-cyclopentyl)-acetic acid;
[0242] [1S-(1α,3α,4α)]-(1-Aminomethyl-3-benzyl-4-methyl-cyclopentyl)-acetic acid;
[0243] [1R-(1α,3α,4α)]-(1-Aminomethyl-3-benzyl-4-methyl-cyclopentyl)-acetic acid;
[0244] (1S-cis)-(1-Aminomethyl-3-methyl-cyclopentyl)-acetic acid;
[0245] (1S-cis)-(1-Aminomethyl-3-ethyl-cyclopentyl)-acetic acid;
[0246] (1S-cis)-(1-Aminomethyl-3-isopropyl-cyclopentyl)-acetic acid;
[0247] (1S-cis)-(1-Aminomethyl-3-tert-butyl-cyclopentyl)-acetic acid;
[0248] (1S-cis)-(1-Aminomethyl-3-phenyl-cyclopentyl)-acetic acid;
[0249] (1S-cis)-(1-Aminomethyl-3-benzyl-cyclopentyl)-acetic acid;
[0250] (1R-cis)-(1-Aminomethyl-3-methyl-cyclopentyl)-acetic acid;
[0251] (1R-cis)-(1-Aminomethyl-3-ethyl-cyclopentyl)-acetic acid;
[0252] (1R-cis)-(1-Aminomethyl-3-isopropyl-cyclopentyl)-acetic acid;
[0253] (1R-cis)-(1-Aminomethyl-3-tert-butyl-cyclopentyl)-acetic acid;
[0254] (1R-cis)-(1-Aminomethyl-3-phenyl-cyclopentyl)-acetic acid;
[0255] (1R-cis)-(1-Aminomethyl-3-benzyl-cyclopentyl)-acetic acid;
[0256] (S)-(1-Aminomethyl-3,3-methyl-cyclopentyl)-acetic acid;
[0257] (S)-(1-Aminomethyl-3,3-diethyl-cyclopentyl)-acetic acid;
[0258] (1-Aminomethyl-3,3,4,4-tetramethyl-cyclopentyl)-acetic acid;
[0259] (1-Aminomethyl-3,3,4,4-tetraethyl-cyclopentyl)-acetic acid;
[0260] (1α,3β,4β)-(1-Aminomethyl-3,4-dimethyl-cyclopentyl)-acetic acid;
[0261] (1α3β,4β)-(1-Aminomethyl-3,4-diethyl-cyclopentyl)-acetic acid;
[0262] (1α,3β,4β)-(1-Aminomethyl-3,4-diisopropyl-cyclopentyl)-acetic acid;
[0263] [1R-(1α,3β,4β)-(1-Aminomethyl-3-ethyl-cyclopentyl)-acetic acid;
[0264] [1S-(1α,3β,4β)]-(1-Aminomethyl-3-ethyl-4-methyl-cyclopentyl)-acetic acid;
[0265] [1R-(1α,3β,4β)]-(1-Aminomethyl-3-isopropyl-4-methyl-cyclopentyl)-acetic acid;
[0266] [1S-(1α,3β,4β)]-(1-Aminomethyl-3-isopropyl-4-methyl-cyclopentyl)-acetic acid;
[0267] [1R-(1α,3β,4β)]-(1-Aminomethyl-3-ethyl-4-isopropyl-cyclopentyl)-acetic acid;
[0268] [1S-(1α,3β,4β)]-(1-Aminomethyl-3-ethyl-4-isopropyl-cyclopentyl)-acetic acid;
[0269] [1R-(1α,3β,4β)]-(1-Aminomethyl-3-tert-butyl-4-methyl-cyclopentyl)-acetic acid;
[0270] [1S-(1α,3β,4β)]-(1-Aminomethyl-3-tert-butyl-4-methyl-cyclopentyl)-acetic acid;
[0271] [1R-(1α,3β,4β)]-(1-Aminomethyl-3-tert-butyl-4-methyl-cyclopentyl)-acetic acid;
[0272] [1S-(1α,3β,4β)]-(1-Aminomethyl-3-tert-butyl-4-ethyl-cyclopentyl)-acetic acid;
[0273] [1R-(1α,3β,4β)]-(1-Aminomethyl-3-tert-butyl-4-isopropyl-cyclopentyl)-acetic acid;
[0274] [1S-(1α,3β,4β)]-(1-Aminomethyl-3-tert-butyl-4-isopropyl-cyclopentyl)-acetic acid;
[0275] (1α,3β,4β)-(1-Aminomethyl-3,4-di-tert-butyl-cyclopentyl)-acetic acid;
[0276] [1R-(1α,3β,4β)]-(1-Aminomethyl-3-methyl-4-phenyl-cyclopentyl)-acetic acid;
[0277] [1S-(1α,3β,4β)]-(1-Aminomethyl-3-methyl-4-phenyl-cyclopentyl)-acetic acid;
[0278] [1R-(1α,3β,4β)]-(1-Aminomethyl-3-benzyl-4-methyl-cyclopentyl)-acetic acid;
[0279] [1S-(1α,3β,4β)]-(1-Aminomethyl-3-benzyl-4-methyl-cyclopentyl)-acetic acid;
[0280] (1R-trans)-(1-Aminomethyl-3-methyl-cyclopentyl)-acetic acid;
[0281] (1R-trans)-(1-Aminomethyl-3-ethyl-cyclopentyl)-acetic acid;
[0282] (1R-trans)-(1-Aminomethyl-3-isopropyl-cyclopentyl)-acetic acid;
[0283] (1R-trans)-(1-Aminomethyl-3-tert-butyl-cyclopentyl)-acetic acid;
[0284] (1R-trans)-(1-Aminomethyl-3-phenyl-cyclopentyl)-acetic acid;
[0285] (1R-trans)-(1-Aminomethyl-3-benzyl-cyclopentyl)-acetic acid;
[0286] (1S-trans)-(1-Aminomethyl-3-methyl-cyclopentyl)-acetic acid;
[0287] (1S-trans)-(1-Aminomethyl-3-ethyl-cyclopentyl)-acetic acid;
[0288] (1S-trans)-(1-Aminomethyl-3-isopropyl-cyclopentyl)-acetic acid;
[0289] (1S-trans)-(1-Aminomethyl-3-tert-butyl-cyclopentyl)-acetic acid;
[0290] (1S-trans)-(1-Aminomethyl-3-phenyl-cyclopentyl)-acetic acid;
[0291] (1S-trans)-(1-Aminomethyl-3-benzyl-cyclopentyl)-acetic acid;
[0292] (R)-(1-Aminomethyl-3,3-dimethyl-cyclopentyl)-acetic acid;
[0293] (R)-(1-Aminomethyl-3,3-diethyl-cyclopentyl)-acetic acid;
[0294] cis-(1-Aminomethyl-3-methyl-cyclobutyl)-acetic acid;
[0295] cis-(1-Aminomethyl-3-ethyl-cyclobutyl)-acetic acid;
[0296] cis-(1-Aminomethyl-3-isopropyl-cyclobutyl)-acetic acid;
[0297] cis-(1-Aminomethyl-3-tert-butyl-cyclobutyl)-acetic acid;
[0298] cis-(1-Aminomethyl-3-phenyl-cyclobutyl)-acetic acid;
[0299] cis-(1-Aminomethyl-3-benzyl-cyclobutyl)-acetic acid;
[0300] trans-(1-Aminomethyl-3-methyl-cyclobutyl)-acetic acid;
[0301] trans-(1-Aminomethyl-3-ethyl-cyclobutyl)-acetic acid;
[0302] trans-(1-Aminomethyl-3-isopropyl-cyclobutyl)-acetic acid;
[0303] trans-(1-Aminomethyl-3-tert-butyl-cyclobutyl)-acetic acid;
[0304] trans-(1-Aminomethyl-3-phenyl-cyclobutyl)-acetic acid;
[0305] trans-(1-Aminomethyl-3-benzyl-cyclobutyl)-acetic acid;
[0306] cis-(1-Aminomethyl-3-ethyl-3-methyl-cyclobutyl)-acetic acid;
[0307] cis-(1-Aminomethyl-3-isopropyl-3-methyl-cyclobutyl)-acetic acid;
[0308] cis-(1-Aminomethyl-3-tert-butyl-3-methyl-cyclobutyl)-acetic acid;
[0309] cis-(1-Aminomethyl-3-methyl-3-phenyl-cyclobutyl)-acetic acid;
[0310] cis-(1-Aminomethyl-3-benzyl-3-methyl-cyclobutyl)-acetic acid;
[0311] trans-(1-Aminomethyl-3-ethyl-3-methyl-cyclobutyl)-acetic acid;
[0312] trans-(1-Aminomethyl-3-isopropyl-3-methyl-cyclobutyl)-acetic acid;
[0313] trans-(1-Aminomethyl-3-tert-butyl-3-methyl-cyclobutyl)-acetic acid;
[0314] trans-(1-Aminomethyl-3-methyl-3-phenyl-cyclobutyl)-acetic acid;
[0315] trans-(1-Aminomethyl-3-benzyl-3-methyl-cyclobutyl)-acetic acid;
[0316] trans-(1-Aminomethyl-3-ethyl-3-isopropyl-cyclobutyl)-acetic acid;
[0317] cis-(1-Aminomethyl-3-tert-butyl-3-ethyl-cyclobutyl)-acetic acid;
[0318] cis-(1-Aminomethyl-3-ethyl-3-phenyl-cyclobutyl)-acetic acid;
[0319] cis-(1-Aminomethyl-3-benzyl-3-ethyl-cyclobutyl)-acetic acid;
[0320] trans-(1-Aminomethyl-3-ethyl-3-isopropyl-cyclobutyl)-acetic acid;
[0321] trans-(1-Aminomethyl-3-tert-butyl-3-ethyl-cyclobutyl)-acetic acid;
[0322] trans-(1-Aminomethyl-3-ethyl-3-phenyl-cyclobutyl)-acetic acid;
[0323] trans-(1-Aminomethyl-3-benzyl-3-ethyl-cyclobutyl)-acetic acid;
[0324] cis-(1-Aminomethyl-3-tert-butyl-3-isopropyl-cyclobutyl)-acetic acid;
[0325] cis-(1-Aminomethyl-3-isopropyl-3-phenyl-cyclobutyl)-acetic acid;
[0326] trans-(1-Aminomethyl-3-benzyl-3-isopropyl-cyclobutyl)-acetic acid;
[0327] cis-(1-Aminomethyl-3-tert-butyl-3-phenyl-cyclobutyl)-acetic acid;
[0328] trans-(1-Aminomethyl-3-benzyl-3-tert-butyl-cyclobutyl)-acetic acid;
[0329] trans-(1-Aminomethyl-3-tert-butyl-3-isopropyl-cyclobutyl)-acetic acid;
[0330] trans-(1-Aminomethyl-3-isopropyl-3-phenyl-cyclobutyl)-acetic acid;
[0331] cis-(1-Aminomethyl-3-benzyl-3-isopropyl-cyclobutyl)-acetic acid;
[0332] trans-(1-Aminomethyl-3-tert-butyl-3-phenyl-cyclobutyl)-acetic acid;
[0333] cis-(1-Aminomethyl-3-benzyl-3-tert-butyl-cyclobutyl)-acetic acid;
[0334] cis-(1-Aminomethyl-3-ethyl-3-methyl-cyclobutyl)-acetic acid;
[0335] (1-Aminomethyl-3,3-dimethyl-cyclobutyl)-acetic acid;
[0336] (1-Aminomethyl-3,3-diethyl-cyclobutyl)-acetic acid;
[0337] (1-Aminomethyl-3,3-diisopropyl-cyclobutyl)-acetic acid;
[0338] (1-Aminomethyl-3,3-di-tert-cyclobutyl)-acetic acid;
[0339] (1-Aminomethyl-3,3-diphenyl-cyclobutyl)-acetic acid;
[0340] (1-Aminomethyl-3,3-dibenzyl-cyclobutyl)-acetic acid;
[0341] (1-Aminomethyl-2,2,4,4-tetramethyl-cyclobutyl)-acetic acid;
[0342] (1-Aminomethyl-2,2,3,3,4,4-hexamethyl-cyclobutyl)-acetic acid;
[0343] (R)-(1-Aminomethyl-2,2-dimethyl-cyclobutyl)-acetic acid;
[0344] (S)-(1-Aminomethyl-2,2-dimethyl-cyclobutyl)-acetic acid;
[0345] (1R-cis)-(1-Aminomethyl-2-methyl-cyclobutyl)-acetic acid;
[0346] [1R-(1α,2α,3α)]-(1-Aminomethyl-2,3-dimethyl-cyclobutyl)-acetic acid;
[0347] (1α,2α,4α)-(1-Aminomethyl-2,4-dimethyl-cyclobutyl)-acetic acid;
[0348] [1R-(1α,2α,3β)]-(1-Aminomethyl-2,3-dimethyl-cyclobutyl)-acetic acid;
[0349] (1α,2α,4β)-(1-Aminomethyl-2,4-dimethyl-cyclobutyl)-acetic acid;
[0350] (1S-trans)-(1-Aminomethyl-2-methyl-cyclobutyl)-acetic acid;
[0351] [1S-(1α,2β,3β)]-(1-Aminomethyl-2,3-dimethyl-cyclobutyl)-acetic acid;
[0352] (1α,2β,4β)-(1-Aminomethyl-2,4-dimethyl-cyclobutyl)-acetic acid;
[0353] [1S-(1α,2β,3α)]-(1-Aminomethyl-2,3-dimethyl-cyclobutyl)-acetic acid;
[0354] (1α,2β,4α)-(1-Aminomethyl-2,4-dimethyl-cyclobutyl)-acetic acid;
[0355] (1R-trans)-(1-Aminomethyl-2-methyl-cyclobutyl)-acetic acid;
[0356] [1R-(1α,2β,3β)]-(1-Aminomethyl-2,3-dimethyl-cyclobutyl)-acetic acid;
[0357] [1R-(1α,2β,4β)]-(1-Aminomethyl-2-ethyl-4-methyl-cyclobutyl)-acetic acid;
[0358] [1R-(1α,2β,3α)]-(1-Aminomethyl-2,3-dimethyl-cyclobutyl)-acetic acid;
[0359] (1α,2β,4α)]-(1-Aminomethyl-2,4-dimethyl-cyclobutyl)-acetic acid;
[0360] (1S-cis)-(1-Aminomethyl-2-methyl-cyclobutyl)-acetic acid;
[0361] [1S-(1α,2α,3α)]-(1-Aminomethyl-2,3-dimethyl-cyclobutyl)-acetic acid;
[0362] [1S-(1α,2α,3α)]-(1-Aminomethyl-2,4-dimethyl-cyclobutyl)-acetic acid;
[0363] [1S-(1α,2β,3α)]-(1-Aminomethyl-2,3-dimethyl-cyclobutyl)-acetic acid;
[0364] (1α,2α,4β)-(1-Aminomethyl-2,4-dimethyl-cyclobutyl)-acetic acid;
[0365] (3S,4S)-(1-Aminomethyl-3,4-dimethyl-cyclopentyl)-acetic acid;
[0366] (3R,4R)-(1-Aminomethyl-3,4-dimethyl-cyclopentyl)-acetic acid;
[0367] (3S,4S)-(1-Aminomethyl-3,4-diethyl-cyclopentyl)-acetic acid;
[0368] (3S,4R)-(1-Aminomethyl-3,4-diethyl-cyclopentyl)-acetic acid;
[0369] (3S,4S)-(1-Aminomethyl-3,4-diisopropyl-cyclopentyl)-acetic acid;
[0370] (3S,4R)-(1-Aminomethyl-3,4-diisopropyl-cyclopentyl)-acetic acid;
[0371] (3S,4S)-(1-Aminomethyl-3,4-di-tert-butyl-cyclopentyl)-acetic acid;
[0372] (3S,4R)-(1-Aminomethyl-3,4-di-tert-butyl-cyclopentyl)-acetic acid;
[0373] (3S,4S)-(1-Aminomethyl-3,4-diphenyl-cyclopentyl)-acetic acid;
[0374] (3S,4R)-(1-Aminomethyl-3,4-diphenyl-cyclopentyl)-acetic acid;
[0375] (3S,4S)-(1-Aminomethyl-3,4-dibenzyl-cyclopentyl)-acetic acid;
[0376] (3S,4R)-(1-Aminomethyl-3,4-dibenzyl-cyclopentyl)-acetic acid;
[0377] [1S-(1α,3α,4β)]-(1-Aminomethyl-3-methyl-4-cyclopentyl)-acetic acid;
[0378] [1R-(1α,3β,4α)]-(1-Aminomethyl-3-methyl-4-ethyl-cyclopentyl)-acetic acid;
[0379] [1R-(1α,3α,4β)]-(1-Aminomethyl-3-methyl-4-ethyl-cyclopentyl)-acetic acid;
[0380] [1S-(1α,3β,4α)]-(1-Aminomethyl-3-methyl-4-ethyl-cyclopentyl)-acetic acid;
[0381] [1S-(1α,3α,4β)]-(1-Aminomethyl-3-methyl-4-isopropyl-cyclopentyl)-acetic acid;
[0382] [1R-(1α,3β,4α)]-(1-Aminomethyl-3-methyl-4-isopropyl-cyclopentyl)-acetic acid;
[0383] [1R-(1α,3α,4β)]-(1-Aminomethyl-3-methyl-4-isopropyl-cyclopentyl)-acetic acid;
[0384] [1S-(1α,3β,4α)]-(1-Aminomethyl-3-methyl-4-isopropyl-cyclopentyl)-acetic acid;
[0385] [1S-(1α,3α,4β)]-(1-Aminomethyl-3-methyl-4-tert-butyl-cyclopentyl)-acetic acid;
[0386] [1R-(1α,3β,4α)]-(1-Aminomethyl-3-methyl-4-tert-butyl-cyclopentyl)-acetic acid;
[0387] [1R-(1α,3α,4β)]-(1-Aminomethyl-3-methyl-4-tert-butyl-cyclopentyl)-acetic acid;
[0388] [1S-(1α,3β,4β)]-(1-Aminomethyl-3-methyl-4-tert-butyl-cyclopentyl)-acetic acid;
[0389] [1S-(1α,3α,4β)]-(1-Aminomethyl-3-methyl-4-phenyl-cyclopentyl)-acetic acid;
[0390] [1R-(1α,3β,4α)]-(1-Aminomethyl-3-methyl-4-phenyl-cyclopentyl)-acetic acid;
[0391] [1R-(1α,3α,4β)]-(1-Aminomethyl-3-methyl-4-phenyl-cyclopentyl)-acetic acid;
[0392] [1S-(1α,3β,4α)]-(1-Aminomethyl-3-methyl-4-phenyl-cyclopentyl)-acetic acid;
[0393] [1S-(1α,3α,4β)]-(1-Aminomethyl-3-benzyl-4-methyl-cyclopentyl)-acetic acid;
[0394] [1R-(1α,3β,4α)]-(1-Aminomethyl-3-benzyl-4-methyl-cyclopentyl)-acetic acid;
[0395] [1R-(1α,3α,4β)]-(1-Aminomethyl-3-benzyl-4-methyl-cyclopentyl)-acetic acid;
[0396] [1S-(1α,3β,4α)]-(1-Aminomethyl-3-benzyl-4-methyl-cyclopentyl)-acetic acid;
[0397] [1S-(1α,3α,4β)]-(1-Aminomethyl-3-ethyl-4-isopropyl-cyclopentyl)-acetic acid;
[0398] [1R-(1α,3β,4α)]-(1-Aminomethyl-3-ethyl-4-isopropyl-cyclopentyl)-acetic acid;
[0399] [1R-(1α,3α,4β)]-(1-Aminomethyl-3-ethyl-4-isopropyl-cyclopentyl)-acetic acid;
[0400] [1S-(1α,3β,4α)]-(1-Aminomethyl-3-ethyl-4-isopropyl-cyclopentyl)-acetic acid;
[0401] [1S-(1α,3α,4β)]-(1-Aminomethyl-3-tert-butyl-4-ethyl-cyclopentyl)-acetic acid;
[0402] [1R-(1α,3β,4α)]-(1-Aminomethyl-3-tert-butyl-4-ethyl-cyclopentyl)-acetic acid;
[0403] [1R-(1α,3α,4β)]-(1-Aminomethyl-3-tert-butyl-4-ethyl-cyclopentyl)-acetic acid;
[0404] [1S-(1α,3β,4α)]-(1-Aminomethyl-3-tert-butyl-4-ethyl-cyclopentyl)-acetic acid;
[0405] [1S-(1α,3α,4β)]-(1-Aminomethyl-3-ethyl-4-phenyl-cyclopentyl)-acetic acid;
[0406] [1R-(1α,3β,4α)]-(1-Aminomethyl-3-ethyl-4-phenyl-cyclopentyl)-acetic acid;
[0407] [1R-(1α,3α,4β)]-(1-Aminomethyl-3-ethyl-4-phenyl-cyclopentyl)-acetic acid;
[0408] [1S-(1α,3β,4α)]-(1-Aminomethyl-3-ethyl-4-phenyl-cyclopentyl)-acetic acid;
[0409] [1S-(1α,3α,4β)]-(1-Aminomethyl-3-benzyl-4-ethyl-cyclopentyl)-acetic acid;
[0410] [1R-(1α,3β,4α)]-(1-Aminomethyl-3-benzyl-4-ethyl-cyclopentyl)-acetic acid;
[0411] [1R-(1α,3α,4β)]-(1-Aminomethyl-3-benzyl-4-ethyl-cyclopentyl)-acetic acid;
[0412] [1S-(1α,3β,4α)]-(1-Aminomethyl-3-benzyl-4-ethyl-cyclopentyl)-acetic acid;
[0413] [1S-(1α,3α,4β)]-(1-Aminomethyl-3-tert-butyl-4-isolpropyl-cyclopentyl)-acetic acid;
[0414] [1R-(1α,3β,4α)]-(1-Aminomethyl-3-tert-butyl-4-isopropyl-cyclopentyl)-acetic acid;
[0415] [1R-(1α,3α,4β)]-(1-Aminomethyl-3-tert-butyl-4-isopropyl-cyclopentyl)-acetic acid;
[0416] [1S-(1α,3β,4α)]-(1-Aminomethyl-3-tert-butyl-4-isopropyl-cyclopentyl)-acetic acid;
[0417] [1S-(1α,3α,4β)]-(1-Aminomethyl-3-isopropyl-4-phenyl-cyclopentyl)-acetic acid;
[0418] [1R-(1α,3β,4α)]-(1-Aminomethyl-3-isopropyl-4-phenyl-cyclopentyl)-acetic acid;
[0419] [1R-(1α,3α,4β)]-(1-Aminomethyl-3-isopropyl-4-phenyl-cyclopentyl)-acetic acid;
[0420] [1S-(1α,3β,4α)]-(1-Aminomethyl-3-isopropyl-4-phenyl-cyclopentyl)-acetic acid;
[0421] [1S-(1α,3α,4β)]-(1-Aminomethyl-3-benzyl-4-isopropyl-cyclopentyl)-acetic acid;
[0422] [1R-(1α,3β,4α)]-(1-Aminomethyl-3-benzyl-4-isopropyl-cyclopentyl)-acetic acid;
[0423] [1R-(1α,3α,4β)]-(1-Aminomethyl-3-benzyl-4-isopropyl-cyclopentyl)-acetic acid;
[0424] [1S-(1α,3β,4α)]-(1-Aminomethyl-3-benzyl-4-isopropyl-cyclopentyl)-acetic acid;
[0425] [1S-(1α,3α,4β)]-(1-Aminomethyl-3-tert-butyl-4-phenyl-cyclopentyl)-acetic acid;
[0426] [1R-(1α,3β,4α)]-(1-Aminomethyl-3-tert-butyl-4-phenyl-cyclopentyl)-acetic acid;
[0427] [1R-(1α,3α,4β)]-(1-Aminomethyl-3-tert-butyl-4-phenyl-cyclopentyl)-acetic acid;
[0428] [1S-(1α,3β,4α)]-(1-Aminomethyl-3-tert-butyl-4-phenyl-cyclopentyl)-acetic acid;
[0429] [1R-(1α,3α,4β)]-(1-Aminomethyl-3-benzyl-4-tert-butyl-cyclopentyl)-acetic acid;
[0430] [1S-(1α,3β,4α)]-(1-Aminomethyl-3-benzyl-4-tert-butyl-cyclopentyl)-acetic acid;
[0431] [1S-(1α,3α,4β)]-(1-Aminomethyl-3-benzyl-4-tert-butyl-cyclopentyl)-acetic acid;
[0432] [1R-(1α,3β,4α)]-(1-Aminomethyl-3-benzyl-4-tert-butyl-cyclopentyl)-acetic acid;
[0433] [1S-(1α,3α,4β)]-(1-Aminomethyl-3-benzyl-4-phenyl-cyclopentyl)-acetic acid;
[0434] [1R-(1α,3β,4α)]-(1-Aminomethyl-3-benzyl-4-phenyl-cyclopentyl)-acetic acid;
[0435] [1R-(1α,3α,4β)]-(1-Aminomethyl-3-benzyl-4-phenyl-cyclopentyl)-acetic acid;
[0436] [1S-(1α,3β,4α)]-(1-Aminomethyl-3-benzyl-4-phenyl-cyclopentyl)-acetic acid;
[0437] (1R-cis)-(1-Aminomethyl-2-methyl-cyclopentyl)-acetic acid;
[0438] (1S-cis)-(1-Aminomethyl-2-methyl-cyclopentyl)-acetic acid;
[0439] (1R-trans)-(1-Aminomethyl-2-methyl-cyclopentyl)-acetic acid;
[0440] (1S-trans)-(1-Aminomethyl-2-methyl-cyclopentyl)-acetic acid;
[0441] (R)-(1-Aminomethyl-2,2-dimethyl-cyclopentyl)-acetic acid;
[0442] (S)-(1-Aminomethyl-2,2-dimethyl-cyclopentyl)-acetic acid;
[0443] (1-Aminomethyl-2,2,5,5-dimethyl-cyclopentyl)-acetic acid;
[0444] (1α,2β,5β)-(1-Aminomethyl-2,5-dimethyl-cyclopentyl)-acetic acid;
[0445] (2S,5S)-(1-Aminomethyl-2,5-dimethyl-cyclopentyl)-acetic acid;
[0446] (1α,2α,5α)-(1-Aminomethyl-2,5-dimethyl-cyclopentyl)-acetic acid;
[0447] [1R-(1α,2α,3α)-(1-Aminomethyl-2,3-dimethyl-cyclopentyl)-acetic acid;
[0448] [1R-(1α,2β,3α)-(1-Aminomethyl-2,3-dimethyl-cyclopentyl)-acetic acid;
[0449] [1R-(1α,2α,3β)-(1-Aminomethyl-2,3-dimethyl-cyclopentyl)-acetic acid;
[0450] [1R-(1β,2α,3β)-(1-Aminomethyl-2,3-dimethyl-cyclopentyl)-acetic acid;
[0451] [1S-(1α,2α,3α)-(1-Aminomethyl-2,3-dimethyl-cyclopentyl)-acetic acid;
[0452] [1S-(1α,2β,3α)-(1-Aminomethyl-2,3-dimethyl-cyclopentyl)-acetic acid;
[0453] [1S-(1α,2α,3β)-(1-Aminomethyl-2,3-dimethyl-cyclopentyl)-acetic acid;
[0454] [1S-(1α,2β,3β)-(1-Aminomethyl-2,3-dimethyl-cyclopentyl)-acetic acid;
[0455] [1R-(1α,2α,4α)-(1-Aminomethyl-2,4-dimethyl-cyclopentyl)-acetic acid;
[0456] [1S-(1α,2α,4α)-(1-Aminomethyl-2,4-dimethyl-cyclopentyl)-acetic acid;
[0457] [1R-(1α,2α,4β)-(1-Aminomethyl-2,4-dimethyl-cyclopentyl)-acetic acid;
[0458] [1S-(1α,2α,4β)-(1-Aminomethyl-2,4-dimethyl-cyclopentyl)-acetic acid;
[0459] [1R-(1α,2β,4α)-(1-Aminomethyl-2,4-dimethyl-cyclopentyl)-acetic acid;
[0460] [1S-(1α,2β,4α)-(1-Aminomethyl-2,4-dimethyl-cyclopentyl)-acetic acid;
[0461] [1R-(1α,2β,4β)-(1-Aminomethyl-2,4-dimethyl-cyclopentyl)-acetic acid;
[0000] and
[0462] [1S-(1α,2β,4β)-(1-Aminomethyl-2,4-dimethyl-cyclopentyl)-acetic acid;
[0463] Other preferred embodiments of the invention methods utilize a compound of the Formula III, IIIC, IIIF, IIIG, or IIIH, wherein R is a sulfonamide selected from —NHSO 2 R 15 or —SO 2 NHR 15 wherein R 15 is straight or branched alkyl or trifluoromethyl.
[0464] Other preferred embodiments of the invention methods utilize a compound of the Formula III, IIIC, IIIF, IIIG, or IIIH that is N-[2-(1-aminomethyl-cyclohexyl)-ethyl]-methanesulfonamide.
[0465] Other preferred embodiments of the invention methods utilize a compound of the Formula III, IIIC, IIIF, IIIG, or IIIH, wherein R is a phosphonic acid, —PO 3 H 2 .
[0466] Other preferred embodiment of the invention methods utilize a compound of the Formula III, IIIC, IIIF, IIIG, or IIIH that is (1-aminomethyl-cyclohexylmethyl)-phosphonic acid and (2-aminomethyl-4-methyl-pentyl)-phosphonic acid.
[0467] Other preferred embodiments of the invention methods utilize a compound of the Formula II, IIIC, IIIF, IIIG, or IIIH, wherein other preferred compounds are those wherein R is a heterocycle selected from:
[0468] Other preferred embodiments of the invention methods are those that utilize a compound of the Formula III, IIIC, IIIF, IIIG, or IIIH, that is C-[1-(1H-tetrazol-5-ylmethyl)cyclohexyl]-methylamine or 4-methyl-2-(1H-tetrazol-5-ylmethyl)-pentylamine.
[0469] Especially preferred embodiments of the invention methods utilize a compound of the Formula III, IIIC, IIIF, IIIG, or IIIH wherein:
[0470] m is an integer of from 0 to 2;
[0471] p is an integer of 2; and
[0472] R is
[0473] Other more preferred embodiments of the invention methods are those that utilize a compound of the Formula III, IIIC, IIIF, IIIG, or IIIH that is 3-(1-aminomethyl-cyclohexylmethyl)-4H-[1,2,4]oxadiazol-5-one, or a pharmaceutically acceptable salt thereof.
[0474] Other more preferred embodiments of the invention methods are those that utilize a compound of the Formula III, IIIC, IIIF, IIIG, or IIIH that is 3-(1-aminomethyl-cyclohexylmethyl)-4H-[1,2,4]oxadiazol-5-one hydrochloride.
[0475] Other more preferred embodiments of the invention methods are those that utilize a compound of the Formula III, IIIC, IIIF, IIIG, or IIIH that is 3-(1-aminomethyl-cycloheptylmethyl)-4H-[1,2,4]oxadiazol-5-one, or a pharmaceutically acceptable salt thereof.
[0476] Other more preferred embodiments of the invention methods are those that utilize a compound of the Formula III, IIIC, IIIF, IIIG, or IIIH that is 3-(1-aminomethyl-cycloheptylmethyl)-4H-[1,2,4]oxadiazol-5-one hydrochloride.
[0477] Other more preferred embodiments of the invention methods are those that utilizes a compound of the Formula III, IIIC, IIIF, IIIG, or IIIH that is C-[1-(1H-tetrazol-5-ylmethyl)-cycloheptyl]-methylamine, or a pharmaceutically acceptable salt thereof.
[0478] Alpha2delta ligands of the Formulas III, IIIC, IIIF, IIIG, and IIIH, and methods of synthesizing them, are described in PCT Patent Application No. WO 99/31075, which is incorporated herein by reference in its entirety.
[0479] Other preferred embodiments of the invention methods utilize an alpha2delta ligand that is a compound of the Formula IV
or a pharmaceutically acceptable salt thereof wherein:
R 1 is hydrogen, straight or branched alkyl of from 1 to 6 carbon atoms or phenyl; R 2 is straight or branched alkyl of from 1 to 8 carbon atoms, straight or branched alkenyl of from 2 to 8 carbon atoms, cycloalkyl of from 3 to 7 carbon atoms, alkoxy of from 1 to 6 carbon atoms, -alkylcycloalkyl, -alkylalkoxy, -alkyl OH -alkylphenyl, -alkylphenoxy, -phenyl or substituted phenyl; and R 1 is straight or branched alkyl of from 1 to 6 carbon atoms or phenyl when R 2 is methyl.
[0483] Other preferred embodiments of the invention methods are those that employ a compound of Formula IV wherein R 1 is hydrogen, and R 2 is alkyl.
[0484] Other preferred embodiments of the invention methods are those that that employ a compound of Formula IV wherein R 1 is methyl, and R 2 is alkyl.
[0485] Other preferred embodiments of the invention methods are those that employ a compound of Formula IV wherein R 1 is methyl, and R 2 is methyl or ethyl.
[0486] Other preferred embodiments of the invention methods are those that employ a compound of Formula IV selected from:
[0487] 3-Aminomethyl-5-methylheptanoic acid;
[0488] 3-Aminomethyl-5-methyl-octanoic acid;
[0489] 3-Aminomethyl-5-methyl-nonanoic acid;
[0490] 3-Aminomethyl-5-methyl-decanoic acid;
[0491] 3-Aminomethyl-5-methyl-undecanoic acid;
[0492] 3-Aminomethyl-5-methyl-dodecanoic acid;
[0493] 3-Aminomethyl-5-methyl-tridecanoic acid;
[0494] 3-Aminomethyl-5-cyclopropyl-hexanoic acid;
[0495] 3-Aminomethyl-5-cyclobutyl-hexanoic acid;
[0496] 3-Aminomethyl-5-cyclopentyl-hexanoic acid;
[0497] 3-Aminomethyl-5-cyclohexyl-hexanoic acid;
[0498] 3-Aminomethyl-5-trifluoromethyl-hexanoic acid;
[0499] 3-Aminomethyl-5-phenyl-hexanoic acid;
[0500] 3-Aminomethyl-5-(2-chlorophenyl)-hexanoic acid;
[0501] 3-Aminomethyl-5-(3-chlorophenyl)-hexanoic acid;
[0502] 3-Aminomethyl-5-(4-chlorophenyl)-hexanoic acid;
[0503] 3-Aminomethyl-5-(2-methoxyphenyl)-hexanoic acid;
[0504] 3-Aminomethyl-5-(3-methoxyphenyl)-hexanoic acid;
[0505] 3-Aminomethyl-5-(4-methoxyphenyl)-hexanoic acid; and
[0506] 3-Aminomethyl-5-(phenylmethyl)-hexanoic acid.
[0507] (3R,4S)-3-Aminomethyl-4,5-dimethyl-hexanoic acid;
[0508] 3-Aminomethyl-4,5-dimethyl-hexanoic acid;
[0509] (3R,4S)-3-Aminomethyl-4,5-dimethyl-hexanoic acid MP;
[0510] (3S,4S)-3-Aminomethyl-4,5-dimethyl-hexanoic acid;
[0511] (3R,4R)-3-Aminomethyl-4,5-dimethyl-hexanoic acid MP;
[0512] 3-Aminomethyl-4-isopropyl-hexanoic acid;
[0513] 3-Aminomethyl-4-isopropyl-heptanoic acid;
[0514] 3-Aminomethyl-4-isopropyl-octanoic acid;
[0515] 3-Aminomethyl-4-isopropyl-nonanoic acid;
[0516] 3-Aminomethyl-4-isopropyl-decanoic acid;
[0517] 3-Aminomethyl-4-phenyl-5-methyl-hexanoic acid;
[0518] (3S,5S)-3-Aminomethyl-5-methoxy-hexanoic acid;
[0519] (3S,5S)-3-Aminomethyl-5-ethoxy-hexanoic acid;
[0520] (3S,5S)-3-Aminomethyl-5-propoxy-hexanoic acid;
[0521] (3S,5S)-3-Aminomethyl-5-isopropoxy-hexanoic acid;
[0522] (3S,5S)-3-Aminomethyl-5-tert-butoxy-hexanoic acid;
[0523] (3S,5S)-3-Aminomethyl-5-fluoromethoxy-hexanoic acid;
[0524] (3S,5S)-3-Aminomethyl-5-(2-fluoro-ethoxy)-hexanoic acid;
[0525] (3S,5S)-3-Aminomethyl-5-(3,3,3-trifluoro-propoxy)-hexanoic acid;
[0526] (3S,5S)-3-Aminomethyl-5-phenoxy-hexanoic acid;
[0527] (3S,5S)-3-Aminomethyl-5-(4-chloro-phenoxy)-hexanoic acid;
[0528] (3S,5S)-3-Aminomethyl-5-(3-chloro-phenoxy)-hexanoic acid;
[0529] (3S,5S)-3-Aminomethyl-5-(2-chloro-phenoxy)-hexanoic acid;
[0530] (3S,5S)-3-Aminomethyl-5-(4-fluoro-phenoxy)-hexanoic acid;
[0531] (3S,5S)-3-Aminomethyl-5-(3-fluoro-phenoxy)-hexanoic acid;
[0532] (3S,5S)-3-Aminomethyl-5-(2-fluoro-phenoxy)-hexanoic acid;
[0533] (3S,5S)-3-Aminomethyl-5-(4-methoxy-phenoxy)-hexanoic acid;
[0534] (3S,5S)-3-Aminomethyl-5-(3-methoxy-phenoxy)-hexanoic acid;
[0535] (3S,5S)-3-Aminomethyl-5-(2-methoxy-phenoxy)-hexanoic acid;
[0536] (3S,5S)-3-Aminomethyl-5-(4-nitro-phenoxy)-hexanoic acid;
[0537] (3S,5S)-3-Aminomethyl-5-(3-nitro-phenoxy)-hexanoic acid;
[0538] (3S,5S)-3-Aminomethyl-5-(2-nitro-phenoxy)-hexanoic acid;
[0539] (3S,5S)-3-Aminomethyl-6-hydroxy-5-methyl-hexanoic acid;
[0540] (3S,5S)-3-Aminomethyl-6-methoxy-5-methyl-hexanoic acid;
[0541] (3S,5S)-3-Aminomethyl-6-ethoxy-5-methyl-hexanoic acid;
[0542] (3S,5S)-3-Aminomethyl-5-methyl-6-propoxy-hexanoic acid;
[0543] (3S,5S)-3-Aminomethyl-6-isopropoxy-5-methyl-hexanoic acid;
[0544] (3S,5S)-3-Aminomethyl-6-tert-butoxy-5-methyl-hexanoic acid;
[0545] (3S,5S)-3-Aminomethyl-6-fluoromethoxy-5-methyl-hexanoic acid;
[0546] (3S,5S)-3-Aminomethyl-6-(2-fluoro-ethoxy)-5-methyl-hexanoic acid;
[0547] (3S,5S)-3-Aminomethyl-5-methyl-6-(3,3,3-trifluoro-propoxy)-hexanoic acid;
[0548] (3S,5S)-3-Aminomethyl-5-methyl-6-phenoxy-hexanoic acid;
[0549] (3S,5S)-3-Aminomethyl-6-(4-chloro-phenoxy)-5-methyl-hexanoic acid;
[0550] (3S,5S)-3-Aminomethyl-6-(3-chloro-phenoxy)-5-methyl-hexanoic acid;
[0551] (3S,5S)-3-Aminomethyl-6-(2-chloro-phenoxy)-5-methyl-hexanoic acid;
[0552] (3S,5S)-3-Aminomethyl-6-(4-fluoro-phenoxy)-5-methyl-hexanoic acid;
[0553] (3S,5S)-3-Aminomethyl-6-(3-fluoro-phenoxy)-5-methyl-hexanoic acid;
[0554] (3S,5S)-3-Aminomethyl-6-(2-fluoro-phenoxy)-5-methyl-hexanoic acid;
[0555] (3S,5S)-3-Aminomethyl-6-(4-methoxy-phenoxy)-5-methyl-hexanoic acid;
[0556] (3S,5S)-3-Aminomethyl-6-(3-methoxy-phenoxy)-5-methyl-hexanoic acid;
[0557] (3S,5S)-3-Aminomethyl-6-(2-methoxy-phenoxy)-5-methyl-hexanoic acid;
[0558] (3S,5S)-3-Aminomethyl-5-methyl 6-(4-trifluoromethyl-phenoxy)-hexanoic acid;
[0559] (3S,5S)-3-Aminomethyl-5-methyl 6-(3-trifluoromethyl-phenoxy)-hexanoic acid;
[0560] (3S,5S)-3-Aminomethyl-5-methyl 6-(2-trifluoromethyl-phenoxy)-hexanoic acid;
[0561] (3S,5S)-3-Aminomethyl-5-methyl 6-(4-nitro-phenoxy)-hexanoic acid;
[0562] (3S,5S)-3-Aminomethyl-5-methyl 6-(3-nitro-phenoxy)-hexanoic acid;
[0563] (3S,5S)-3-Aminomethyl-5-methyl 6-(2-nitro-phenoxy)-hexanoic acid;
[0564] (3S,5S)-3-Aminomethyl-6-benzyloxy-5-methyl-hexanoic acid;
[0565] (3S,5S)-3-Aminomethyl-7-hydroxy-5-methyl-heptanoic acid;
[0566] (3S,5S)-3-Aminomethyl-7-methoxy-5-methyl-heptanoic acid;
[0567] (3S,5S)-3-Aminomethyl-7-ethoxy-5-methyl-heptanoic acid;
[0568] (3S,5S)-3-Aminomethyl-5-methyl-7-propoxy-heptanoic acid;
[0569] (3S,5S)-3-Aminomethyl-7-isopropoxy-5-methyl-heptanoic acid;
[0570] (3S,5S)-3-Aminomethyl-7-tert-butoxy-5-methyl-heptanoic acid;
[0571] (3S,5S)-3-Aminomethyl-7-fluoromethoxy-5-methyl-heptanoic acid;
[0572] (3S,5S)-3-Aminomethyl-7-(2-fluoro-ethoxy)-5-methyl-heptanoic acid;
[0573] (3S,5S)-3-Aminomethyl-5-methyl-7-(3,3,3-trifluoro-propoxy)-heptanoic acid;
[0574] (3S,5S)-3-Aminomethyl-7-benzyloxy-5-methyl-heptanoic acid;
[0575] (3S,5S)-3-Aminomethyl-5-methyl-7-phenoxy-heptanoic acid;
[0576] (3S,5S)-3-Aminomethyl-7-(4-chloro-phenoxy)-5-methyl-heptanoic acid;
[0577] (3S,5S)-3-Aminomethyl-7-(3-chloro-phenoxy)-5-methyl-heptanoic acid;
[0578] (3S,5S)-3-Aminomethyl-7-(2-chloro-phenoxy)-5-methyl-heptanoic acid;
[0579] (3S,5S)-3-Aminomethyl-7-(4-fluoro-phenoxy)-5-methyl-heptanoic acid;
[0580] (3S,5S)-3-Aminomethyl-7-(3-fluoro-phenoxy)-5-methyl-heptanoic acid;
[0581] (3S,5S)-3-Aminomethyl-7-(2-fluoro-phenoxy)-5-methyl-heptanoic acid;
[0582] (3S,5S)-3-Aminomethyl-7-(4-methoxy-phenoxy)-5-methyl-heptanoic acid;
[0583] (3S,5S)-3-Aminomethyl-7-(3-methoxy-phenoxy)-5-methyl-heptanoic acid;
[0584] (3S,5S)-3-Aminomethyl-7-(2-methoxy-phenoxy)-5-methyl-heptanoic acid;
[0585] (3S,5S)-3-Aminomethyl-5-methyl-7-(4-trifluoromethyl-phenoxy)-heptanoic acid;
[0586] (3S,5S)-3-Aminomethyl-5-methyl-7-(3-trifluoromethyl-phenoxy)-heptanoic acid;
[0587] (3S,5S)-3-Aminomethyl-5-methyl-7-(2-trifluoromethyl-phenoxy)-heptanoic acid;
[0588] (3S,5S)-3-Aminomethyl-5-methyl-7-(4-nitro-phenoxy)-heptanoic acid;
[0589] (3S,5S)-3-Aminomethyl-5-methyl-7-(3-nitro-phenoxy)-heptanoic acid;
[0590] (3S,5S)-3-Aminomethyl-5-methyl-7-(2-nitro-phenoxy)-heptanoic acid;
[0591] (3S,5S)-3-Aminomethyl-5-methyl-6-phenyl-hexanoic acid;
[0592] (3S,5S)-3-Aminomethyl-6-(4-chloro-phenyl)-5-methyl-hexanoic acid;
[0593] (3S,5S)-3-Aminomethyl-6-(3-chloro-phenyl)-5-methyl-hexanoic acid;
[0594] (3S,5S)-3-Aminomethyl-6-(2-chloro-phenyl)-5-methyl-hexanoic acid;
[0595] (3S,5S)-3-Aminomethyl-6-(4-methoxy-phenyl)-5-methyl-hexanoic acid;
[0596] (3S,5S)-3-Aminomethyl-6-(3-methoxy-phenyl)-5-methyl-hexanoic acid;
[0597] (3S,5S)-3-Aminomethyl-6-(2-methoxy-phenyl)-5-methyl-hexanoic acid;
[0598] (3S,5S)-3-Aminomethyl-6-(4-fluoro-phenyl)-5-methyl-hexanoic acid;
[0599] (3S,5S)-3-Aminomethyl-6-(3-fluoro-phenyl)-5-methyl-hexanoic acid;
[0600] (3S,5S)-3-Aminomethyl-6-(2-fluoro-phenyl)-5-methyl-hexanoic acid;
[0601] (3S,5R)-3-Aminomethyl-5-methyl-7-phenyl-heptanoic acid;
[0602] (3S,5R)-3-Aminomethyl-7-(4-chloro-phenyl)-5-methyl-heptanoic acid;
[0603] (3S,5R)-3-Aminomethyl-7-(3-chloro-phenyl)-5-methyl-heptanoic acid;
[0604] (3S,5R)-3-Aminomethyl-7-(2-chloro-phenyl)-5-methyl-heptanoic acid;
[0605] (3S,5R)-3-Aminomethyl-7-(4-methoxy-phenyl)-5-methyl-heptanoic acid;
[0606] (3S,5R)-3-Aminomethyl-7-(3-methoxy-phenyl)-5-methyl-heptanoic acid;
[0607] (3S,5R)-3-Aminomethyl-7-(2-methoxy-phenyl)-5-methyl-heptanoic acid;
[0608] (3S,5R)-3-Aminomethyl-7-(4-fluoro-phenyl)-5-methyl-heptanoic acid;
[0609] (3S,5R)-3-Aminomethyl-7-(3-fluoro-phenyl)-5-methyl-heptanoic acid;
[0610] (3S,5R)-3-Aminomethyl-7-(2-fluoro-phenyl)-5-methyl-heptanoic acid;
[0611] (3S,5R)-3-Aminomethyl-5-methyl-oct-7-enoic acid;
[0612] (3S,5R)-3-Aminomethyl-5-methyl-non-8-enoic acid;
[0613] (E)-(3S,5S)-3-Aminomethyl-5-methyl-oct-6-enoic acid;
[0614] (Z)-(3S,5S)-3-Aminomethyl-5-methyl-oct-6-enoic acid;
[0615] (Z)-(3S,5S)-3-Aminomethyl-5-methyl-non-6-enoic acid;
[0616] (E)-(3S,5S)-3-Aminomethyl-5-methyl-non-6-enoic acid;
[0617] (E)-(3S,5R)-3-Aminomethyl-5-methyl-non-7-enoic acid;
[0618] (Z)-(3S,5R)-3-Aminomethyl-5-methyl-non-7-enoic acid;
[0619] (Z)-(3S,5R)-3-Aminomethyl-5-methyl-dec-7-enoic acid;
[0620] (E)-(3S,5R)-3-Aminomethyl-5-methyl-undec-7-enoic acid;
[0621] (3S,5S)-3-Aminomethyl-5,6,6-trimethyl-heptanoic acid;
[0622] (3S,5S)-3-Aminomethyl-5,6-dimethyl-heptanoic acid;
[0623] (3S,5S)-3-Aminomethyl-5-cyclopropyl-hexanoic acid;
[0624] (3S,5S)-3-Aminomethyl-5-cyclobutyl-hexanoic acid;
[0625] (3S,5S)-3-Aminomethyl-5-cyclopentyl-hexanoic acid;
[0626] (3S,5S)-3-Aminomethyl-5-cyclohexyl-hexanoic acid;
[0627] (3S,5R)-3-Aminomethyl-5-methyl-heptanoic acid;
[0628] (3S,5R)-3-Aminomethyl-5-methyl-octanoic acid;
[0629] (3S,5R)-3-Aminomethyl-5-methyl-nonanoic acid;
[0630] (3S,5R)-3-Aminomethyl-5-methyl-decanoic acid;
[0631] (3S,5R)-3-Aminomethyl-5-methyl-undecanoic acid;
[0632] (3S,5R)-3-Aminomethyl-5-methyl-dodecanoic acid;
[0633] (3S,5R)-3-Aminomethyl-5,9-dimethyl-decanoic acid;
[0634] (3S,5R)-3-Aminomethyl-5,7-dimethyl-octanoic acid;
[0635] (3S,5R)-3-Aminomethyl-5,8-dimethyl-nonanoic acid;
[0636] (3S,5R)-3-Aminomethyl-6-cyclopropyl-5-methyl-hexanoic acid;
[0637] (3S,5R)-3-Aminomethyl-6-cyclobutyl-5-methyl-hexanoic acid;
[0638] (3S,5R)-3-Aminomethyl-6-cyclopentyl-5-methyl-hexanoic acid;
[0639] (3S,5R)-3-Aminomethyl-6-cyclohexyl-5-methyl-hexanoic acid;
[0640] (3S,5R)-3-Aminomethyl-7-cyclopropyl-5-methyl-heptanoic acid;
[0641] (3S,5R)-3-Aminomethyl-7-cyclobutyl-5-methyl-heptanoic acid;
[0642] (3S,5R)-3-Aminomethyl-7-cyclopentyl-5-methyl-heptanoic acid;
[0643] (3S,5R)-3-Aminomethyl-7-cyclohexyl-5-methyl-heptanoic acid;
[0644] (3S,5R)-3-Aminomethyl-8-cyclopropyl-5-methyl-octanoic acid;
[0645] (3S,5R)-3-Aminomethyl-8-cyclobutyl-5-methyl-octanoic acid;
[0646] (3S,5R)-3-Aminomethyl-8-cyclopentyl-5-methyl-octanoic acid;
[0647] (3S,5R)-3-Aminomethyl-8-cyclohexyl-5-methyl-octanoic acid;
[0648] (3S,5S)-3-Aminomethyl-6-fluoro-5-methyl-hexanoic acid;
[0649] (3S,5S)-3-Aminomethyl-7-fluoro-5-methyl-heptanoic acid;
[0650] (3S,5R)-3-Aminomethyl-8-fluoro-5-methyl-octanoic acid;
[0651] (3S,5R)-3-Aminomethyl-9-fluoro-5-methyl-nonanoic acid;
[0652] (3S,5S)-3-Aminomethyl-7,7,7-trifluoro-5-methyl-heptanoic acid;
[0653] (3S,5R)-3-Aminomethyl-8,8,8-trifluoro-5-methyl-octanoic acid;
[0654] (3S,5R)-3-Aminomethyl-5-methyl-8-phenyl-octanoic acid;
[0655] (3S,5S)-3-Aminomethyl-5-methyl-6-phenyl-hexanoic acid; and
[0656] (3S,5R)-3-Aminomethyl-5-methyl-7-phenyl-heptanoic acid.
[0657] Alpha2delta ligands of the Formula IV, and methods of synthesizing them are described in PCT Patent Application No. WO 00/76958, which is incorporated herein by reference in its entirety.
[0658] Other preferred embodiments of the invention methods utilize an alpha2delta ligand which is a compound of the Formula (IXA) or (IXB)
or a pharmaceutically acceptable salt thereof, wherein:
n is an integer of from 0 to 2; R is sulfonamide,
amide, phosphonic acid, heterocycle, sulfonic acid, or hydroxamic acid;
A is hydrogen or methyl; and
a straight or branched alkyl of from 1 to 11 carbons, or —(CH 2 ) 1-4- Y—(CH 2 ) 0-4- phenyl wherein Y is —O—, —S—, —NR′ 3 wherein:
R′ 3 is alkyl of from 1 to 6 carbons, cycloalkyl of from 3 to 8 carbons, benzyl or phenyl wherein benzyl or phenyl can be unsubstituted or substituted with from 1 to 3 substituents each independently selected from alkyl, alkoxy, halogen, hydroxy, carboxy, carboalkoxy, trifluoromethyl, and nitro.
[0669] Other preferred embodiments of the invention methods utilize an alpha2delta ligand that is a compound of the Formula (IXA) or (IXB), wherein R is a sulfonamide selected from —NHSO 2 R 15 and —SO 2 NHR 15 , wherein R 15 is straight or branched alkyl or trifluoromethyl.
[0670] Other preferred embodiments of the invention methods utilize a compound of the Formula (IXA) or (IXB) selected from:
[0671] 4-Methyl-2-(1H-tetrazol-5-ylmethyl)-pentylamine;
[0672] 3-(2-Aminomethyl-4-methyl-pentyl)-4H-[1,2,4]oxadiazole-5-thione, HCl;
[0673] (2-Aminomethyl-4-methyl-pentyl)-phosphonic acid;
[0674] 3-(3-Amino-2-cyclopentyl-propyl)-4H-[1,2,4]oxadiazol-5-one;
[0675] 3-(3-Amino-2-cyclopentyl-propyl)-4H-[1,2,4]thiadiazol-5-one;
[0676] 2-Cyclopentyl-3-(2-oxo-2,3-dihydro-2λ 4 -[1,2,3,5]oxathiadiazol-4-yl)-propylamine;
[0677] 3-(3-Amino-2-cyclobutyl-propyl)-4H-[1,2,4]oxadiazol-5-one;
[0678] 3-(3-Amino-2-cyclobutyl-propyl)-4H-[1,2,4]thiadiazol-5-one; and
[0679] 2-Cyclobutyl-3-(2-oxo-2,3-dihydro-2λ 4 -[1,2,3,5]oxathiadiazol-4-yl)-propylamine.
[0680] Other preferred embodiments of the invention methods utilize a compound of the Formula (IXA) or (IXB), wherein R is a phosphonic acid, —PO 3 H 2 .
[0681] Other preferred embodiments of the invention methods utilize a compound of the Formula (IXA) or (IXB), wherein R is
[0682] Other preferred embodiments of the invention methods utilize a compound of the Formula (IXA) or (IXB) wherein R is
[0683] Other preferred embodiments of the invention methods utilize a compound of the Formula (IXA) or (IXB) that is 3-(2-aminomethyl-4-methyl-pentyl)-4H-[1,3,4]oxadiazol-5-one, or a pharmaceutically acceptable salt thereof.
[0684] Other preferred embodiments of the invention methods utilize a compound of the Formula (IXA) or (IXB) that is 3-(2-aminomethyl-4-methyl-pentyl)-4H-[1,2,4]oxadiazol-5-one hydrochloride.
[0685] Alpha2delta ligands of the Formulas (IXA) and (IXB), and methods of synthesizing them, are described in PCT Patent Application No. WO 99/31074. This application is incorporated herein by reference in its entirety.
[0686] Other preferred embodiments of the invention methods utilize an alpha2delta ligand that is a compound of the Formula V, VI, VII, or VIII
or a pharmaceutically acceptable salt thereof, wherein n is integer of from 1 to 4, where there are stereocenters, each center may be independently R or S.
[0687] Other preferred embodiments of the invention methods utilize a compound of the Formula V, VI, VII, or VIII, or a pharmaceutically acceptable salt thereof, wherein n is an integer of from 2 to 4.
[0688] Other preferred embodiments of the invention methods utilize a compound of the Formula V or a pharmaceutically acceptable salt thereof.
[0689] Other preferred embodiments of the invention methods utilize a compound of the Formula V, VI, VII, or VIII, or a pharmaceutically acceptable salt thereof, that is selected from the following compounds and their pharmaceutically acceptable salts:
[0690] (1α,6α,8β)(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid;
[0691] (2-Aminomethyl-octahydro-inden-2-yl)-acetic acid;
[0692] (2-Aminomethyl-octahydro-pentalen-2-yl)-acetic acid;
[0693] (2-Aminomethyl-octahydro-pentalen-2-yl)-acetic acid;
[0694] (3-Aminomethyl-bicyclo[3.2.0]hept-3-yl )-acetic acid;
[0695] (3-Aminomethyl-bicyclo[3.2.0]hept-3-yl )-acetic acid;
[0696] (2-Aminomethyl-octahydro-inden-2-yl)-acetic acid;
[0697] (1α,5β)(3-Aminomethyl-bicyclo[3.1.0]hex-3-yl)-acetic acid,
[0698] (1α,5β)(3-Aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid,
[0699] (1α,5β)(2-Aminomethyl-octahydro-pentalen-2-yl)-acetic acid,
[0700] (1α,6β)(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid,
[0701] (1α,7β)(2-Aminomethyl-decahydro-azulen-2-yl)-acetic acid,
[0702] (1α,5β)(3-Aminomethyl-bicyclo[3.1.0]hex-3-yl)-acetic acid,
[0703] (1α,5β)(3-Aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid,
[0704] (1α,5β)(2-Aminomethyl-octahydro-pentalen-2-yl)-acetic acid,
[0705] (1α,6β)(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid,
[0706] (1α,7β)(2-Aminomethyl-decahydro-azulen-2-yl)-acetic acid,
[0707] (1α,3α,5α)(3-Aminomethyl-bicyclo[3.1.0]hex-3-yl)-acetic acid,
[0708] (1α,3α,5α)(2-Aminomethyl-octahydro-pentalen-2-yl)-acetic acid,
[0709] (1α,6α,8α)(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid,
[0710] (1α,7α,9α)(2-Aminomethyl-decahydro-azulen-2-yl)-acetic acid,
[0711] (1α,3α,5α)(3-Aminomethyl-bicyclo[3.1.0]hex-3-yl)-acetic acid,
[0712] (1α,3β,5α)(3-Aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid,
[0713] (1α,3β,5α)(2-Aminomethyl-octahydro-pentalen-2-yl )-acetic acid,
[0714] (1α,6α,8β)(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid,
[0715] (1α,7α,9β)(2-Aminomethyl-decahydro-azulen-2-yl)-acetic acid,
[0716] ((1R,3R,6R)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
[0717] ((1R,3S,6R)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
[0718] ((1S,3S,6S)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
[0719] ((1S,3R,6S)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
[0720] ((1R,3R,6S)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
[0721] ((1R,3S,6S)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
[0722] ((1S,3S,6R)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
[0723] ((1S,3R,6R)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
[0724] ((3αR,5R,7αS)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
[0725] ((3αR,5S,7αS)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
[0726] ((3αS,5S,7αR)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
[0727] ((3αS,5R,7αR)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
[0728] ((2R,4αS,8αR)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,
[0729] ((2S,4αS,8αR)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,
[0730] ((2S,4αR,8αS)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,
[0731] ((2R,4αR,8αS)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,
[0732] ((2R,4αS,9αR)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,
[0733] ((2S,4αS,9αR)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,
[0734] ((2S,4αR,9αS)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,
[0735] ((2R,4αR,9αS)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,
[0736] ((1R,3R,6S)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
[0737] ((1R,3S,6S)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
[0738] ((1S,3S,6R)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
[0739] ((1S,3R,6R)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
[0740] ((1R,3R,6R)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
[0741] ((1R,3S,6R)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
[0742] ((1S,3S,6S)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
[0743] ((1S,3R,6S)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
[0744] ((3αR,5R,7αR)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
[0745] ((3αR,5S,7αR)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
[0746] ((3αS,5S,7αS)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
[0747] ((3αS,5R,7αS)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
[0748] ((2R,4αR,8αR)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,
[0749] ((2S,4αS,8αR)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,
[0750] ((2S,4αR,8αS)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,
[0751] ((2R,4αS,8αS)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,
[0752] ((2R,4αR,9αR)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,
[0753] ((2S,4αR,9αR)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,
[0754] ((2S,4αS,9αS)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid, and
[0755] ((2R,4αS,9αS)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid.
[0756] Other preferred embodiments of the invention methods utilize an alpha2delta ligand of the Formula V, VI, VII, or VIII that is (1α,3α,5α)(3-aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid, or a pharmaceutically acceptable salt thereof.
[0757] Other preferred embodiments of the invention methods utilize an alpha2delta ligand of the Formula V, VI, VII, or VIII that is (1α,3α,5α)(3-aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid hydrochloride.
[0758] PCT Patent Application No. WO 01/28978, which is incorporated herein by reference in its entirety, describes alpha2delta ligands that are compounds of the Formulas V, VI, VII, and VIII, and methods of synthesizing them.
[0759] Other preferred embodiments of the invention methods utilize an alpha2delta ligand that is selected from the following compounds and their pharmaceutically acceptable salts:
3-(1-aminomethyl-cyclohexylmethyl)-4H-[1,2,4]oxadiazol-5-one; (S,S)-(1-aminomethyl-3,4-dimethyl-cyclopentyl)-acetic acid; (R,S)-3-aminomethyl-5-methyl-octanoic acid; (S,R)-3-aminomethyl-5-methyl-octanoic acid; (3-aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid; (3-aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid, wherein the cyclobutyl ring is trans to the methylamine group; and C-[1-(1 H-tetrazol-5-ylmethyl)-cycloheptyl]-methylamine.
[0767] These compounds can be prepared as described below or in PCT Patent Application WO 99/21824, published May 6, 1999, PCT Patent Application WO 00/76958, published Dec. 21, 2000, or PCT Patent Application WO 01/28978, published April 26, 2001. These applications are incorporated herein by reference in their entireties.
[0768] Other alpha2delta ligands that can be used in preferred embodiments of the invention methods are described in PCT Patent Application No. WO 99/31057, which is incorporated herein by reference in its entirety. Such alpha2delta ligands are compounds of the Formulas (XII) and (XIII)
or a pharmaceutically acceptable salt thereof wherein:
n is an integer of from 0 to 2; R is sulfonamide,
amide, phosphonic acid, heterocycle, sulfonic acid, or hydroxamic acid; and
X is —O—, —S—, —S(O)—, —S(O) 2 —, or NR′ 1 wherein R′ 1 is hydrogen, straight or branched alkyl of from 1 to 6 carbons, benzyl, —C(O)R′ 2 wherein R′ 2 is straight or branched alkyl of 1 to 6 carbons, benzyl or phenyl or —CO 2 R′ 3 wherein R′ 3 is straight or branched alkyl of from 1 to 6 carbons, or benzyl wherein the benzyl or phenyl groups can be unsubstituted or substituted by from 1 to 3 substituents selected from halogen, trifluoromethyl, and nitro.
[0777] Other alpha2delta ligands that may be utilized in preferred embodiments of the invention methods are described, along with methods of synthesizing them, in PCT Patent Application No. WO 98/17627, which is incorporated herein by reference in its entirety. Such alpha2delta ligands are compounds of the formula
or a pharmaceutically acceptable salt thereof wherein:
R is hydrogen or lower alkyl; R 1 is hydrogen or lower alkyl;
a straight or branched alkyl of from 7 to 11 carbon atoms, or —(CH 2 ) (1-4) —X—(CH 2 ) (0-4) -phenyl wherein X is —O—, —S—, —NR 3 wherein R 3 is alkyl of from 1 to 6 carbons, cycloalkyl of from 3 to 8 carbons, benzyl or phenyl; wherein phenyl and benzyl can be unsubstituted or substituted with from 1 to 3 substituents each independently selected from alkyl, alkoxy, halogen, hydroxy, carboxy, carboalkoxy, trifluoromethyl, amino, and nitro.
[0783] Other alpha2delta ligands that can be utilized in preferred embodiments of the invention methods are described, along with methods 5 of synthesizing them, in PCT Patent Application No. WO 99/61424, which is incorporated herein by reference in its entirety. Such alpha2delta ligands are compounds of the formulas (1), (2), (3), (4), (5), (6), (7), and (8)
and the pharmaceutically acceptable salts and prodrugs of such compounds wherein:
[0784] R 1 to R 10 are each independently selected from hydrogen or a 15 straight or branched alkyl of from 1 to 6 carbons, benzyl, or phenyl;
[0785] m is an integer of from 0 to 3;
[0786] n is an integer of from 1 to 2;
[0787] o is an integer of from 0 to 3;
[0788] p is an integer of from 1 to 2;
[0789] q is an integer of from 0 to 2;
[0790] r is an integer of from 1 to 2;
[0791] s is an integer of from 1 to 3;
[0792] t is an integer of from 0 to 2; and
[0793] u is an integer of from 0 to 1.
[0794] Other alpha2delta ligands that can be utilized in preferred embodiments of the invention methods are described, along with methods of synthesizing them, in U.S. Provisional Patent Application No. 60/368,413, filed on Mar. 28, 2002. Such alpha2delta ligands are compounds of the formulas X, XA, XB, XI, XIA, XIB and XB-1, as described below, and their pharmaceutically acceptable salts.
[0795] Compounds of the formula X have the formula
wherein R 1 is hydrogen or (C 1 -C 3 )alkyl optionally substituted with from one to five fluorine atoms;
[0796] R 2 is hydrogen or (C 1 -C 3 )alkyl optionally substituted with from one to five fluorine atoms;
[0797] R 3 is (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 1 -C 3 )alkyl, phenyl, phenyl-(C 1 -C 3 )alkyl, pyridyl, pyridyl-(C 1 -C 3 )alkyl, phenyl-N(H)—, or pyridyl-N(H)—, wherein each of the foregoing alkyl moieties can be optionally substituted with from one to five fluorine atoms, preferably with from zero to three fluorine atoms, and wherein said phenyl and said pyridyl and the phenyl and pyridyl moieties of said phenyl-(C 1 -C 3 )alkyl and said pyridyl-(C 1 -C 3 )alkyl, respectively, can be optionally substituted with from one to three substituents, preferably with from zero to two substituents, independently selected from chloro, fluoro, amino, nitro, cyano, (C 1 -C 3 )alkylamino, (C 1 -C 3 )alkyl optionally substituted with from one to three fluorine atoms and (C 1 -C 3 )alkoxy optionally substituted with from one to three fluorine atoms;
[0798] with the proviso that when R 1 is hydrogen, R 2 is not hydrogen.
[0799] Compounds of the formula XI have the formula
wherein R 1 , R 2 , and R 3 are defined as above in the definition of compounds of the formula X.
[0800] Compounds of the formula XA have the formula
wherein R 3 is defined as above above in the definition of compounds of the formula X.
[0801] Compounds of the formula XIA have the formula
wherein R 3 is defined as above above in the definition of compounds of the formula X.
[0802] Compounds of the formula XIB have the formula
wherein R 1 , R 2 , and R 3 are defined as above above in the definition of compounds of the formula X.
[0803] Compounds of the formula XB have the formula
wherein R 1 , R 2 , and R 3 are defined as above above in the definition of compounds of the formula X.
[0804] Compounds of the formula XB-1 have the formula
[0805] wherein R 3 is defined as above above in the definition of compounds of the formula X.
[0806] All U.S. patents and WO publications referenced above are incorporated herein by reference in their entireties.
[0807] It should be appreciated that the terms “uses”, “utilizes”, and “employs” are used interchangeably when describing an embodiment of the present invention.
[0808] The phrase “lower alkyl” means a straight or branched alkyl group or radical having from 1 to 6 carbon atoms, and includes methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, and the like.
[0809] The term “alkyl”, as used herein, unless otherwise indicated, includes saturated monovalent hydrocarbon radicals having straight, branched or cyclic moieties or combinations thereof. Examples of “alkyl” groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, iso- sec- and tert-butyl, pentyl, hexyl, heptyl, 3-ethylbutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornyl, and the like.
[0810] The cycloalkyl groups are saturated monovalent carbocyclic groups containing from 3 to 8 carbons and are selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl, unless otherwise stated.
[0811] The benzyl and phenyl groups may be unsubstituted or substituted by from 1 to 3 substituents selected from hydroxy, amino, carboxy, carboalkoxy, halogen, CF 3 , nitro, alkyl, and alkoxy. Preferred substituents are fluorine and chlorine.
[0812] Carboalkoxy is —COOalkyl wherein alkyl is as described above. Preferred carboalokoxy groups are carbomathoxy and carboethoxy.
[0813] The term “alkoxy”, as used herein, unless otherwise indicated, means “alkyl-O—”, wherein “alkyl” is as defined above. Examples of “alkoxy” groups include, but are not limited to, methoxy, ethoxy, propoxy, butoxy and pentoxy.
[0814] The term “alkenyl”, as used herein, unless otherwise indicated, includes unsaturated hydrocarbon radicals having one or more double bonds connecting two carbon atoms, wherein said hydrocarbon radical may have straight, branched or cyclic moieties or combinations thereof. Examples of “alkenyl” groups include, but are not limited to, ethenyl, propenyl, butenyl, pentenyl, and dimethylpentyl, and include E and Z forms where applicable.
[0815] The term “aryl”, as used herein, unless otherwise indicated, includes an aromatic ring system with no heteroatoms, which can be either unsubstituted or substituted with one, two or three substituents selected from the group consisting of halo, (C 1 -C 4 )alkyl optionally substituted with from one to three fluorine atoms and (C 1 -C 4 )alkoxy optionally substituted with from one to three fluorine atoms.
[0816] The term “aryloxy”, as used herein, unless otherwise indicated, means “aryl-O—”, wherein “aryl” is as defined above.
[0817] The term “heteroaryl”, as used herein, unless otherwise indicated, includes an aromatic heterocycle containing five or six ring members, of which from 1 to 4 can be heteroatoms selected, independently, from N, S and O, and which rings can be unsubstituted, monosubstituted or disubstituted with substituents selected, independently, from the group consisting of halo, (C 1 -C 4 )alkyl, and (C 1 -C 4 )alkoxy, optionally substituted with from one to three fluorine atoms.
[0818] The term “heteroaryloxy”, as used herein, unless otherwise indicated, means “heteroaryl-O”, wherein heteroaryl is as defined above.
[0819] The term “one or more substituents”, as used herein, refers to a number of substituents that equals from one to the maximum number of substituents possible based on the number of available bonding sites.
[0820] The terms “halo” and “halogen”, as used herein, unless otherwise indicated, include, fluoro, chloro, bromo and iodo.
[0821] The term “treating”, as used herein, refers to reversing, alleviating, inhibiting the progress of, or preventing the disorder or condition to which such term applies, or preventing one or more symptoms of such condition or disorder. The term “treatment”, as used herein, refers to the act of treating, as “treating” is defined immediately above.
[0822] The term “methylene”, as used herein, means —CH 2 —.
[0823] The term “ethylene”, as used herein, means —CH 2 CH 2 —.
[0824] The term “propylene”, as used herein, means —CH 2 CH 2 CH 2 —.
[0825] “Halogen” or “halo” includes fluorine, chlorine, bromine, and iodine.
[0826] Sulfonamides are those of formula —NHSO 2 R 15 or —SO 2 NHR 15 wherein R 15 is a straight or branched alkyl group of from 1 to 6 carbons or a trifluoromethyl.
[0827] Amides are compounds of formula —NHCOR 12 wherein R 12 is straight or branched alkyl of from 1 to 6 carbons, benzyl, and phenyl.
[0828] Phosphonic acids are —PO 3 H 2 .
[0829] Sulfonic acids are —SO 3 H .
[0830] Hydroxamic acid is
[0831] Heterocycles are groups of from 1 to 2 rings, the monocyclic rings having from 4 to 7 ring members and the bicyclic ring having from 7 to 12 ring members, wherein sucg rings contain from 1 to 6 heteroatoms selected from oxygen, nitrogen, and sulfur, with the proviso that there are no two adjacent ring members that are oxygen.
[0832] Preferred heterocycles are
[0833] Compounds of formulas I-XI-B (i.e., compounds of the formulas I, II, III, IV, V, VI, VII, VIII, IX, X, XA, XB, XB-1, XI, XIA, and XIB) may contain chiral centers and therefore may exist in different enantiomeric and diastereomeric forms. Individual isomers can be obtained by known methods, such as optical resolution, optically selective reaction, or chromatographic separation in the preparation of the final product or its intermediate. This invention relates to all optical isomers and all stereoisomers of compounds of the formulas I-XIB, both as racemic mixtures and as individual enantiomers and diastereoismers of such compounds, and mixtures thereof, and to all pharmaceutical compositions and methods of treatment defined above that contain or employ them, respectively. Individual enantiomers of the compounds of formula I may have advantages, as compared with the racemic mixtures of these compounds, in the treatment of various disorders or conditions.
[0834] In so far as the compounds of formulas I-XIB of this invention are basic compounds, they are all capable of forming a wide variety of different salts with various inorganic and organic acids. Although such salts must be pharmaceutically acceptable for administration to animals, it is often desirable in practice to initially isolate the base compound from the reaction mixture as a pharmaceutically unacceptable salt and then simply convert to the free base compound by treatment with an alkaline reagent and thereafter convert the free base to a pharmaceutically acceptable acid addition salt. The acid addition salts of the base compounds of this invention are readily prepared by treating the base compound with a substantially equivalent amount of the chosen mineral or organic acid in an aqueous solvent or in a suitable organic solvent, such as methanol or ethanol. Upon careful evaporation of the solvent, the desired solid salt is readily obtained. The acids which are used to prepare the pharmaceutically acceptable acid addition salts of the aforementioned base compounds of this invention are those which form non-toxic acid addition salts, i.e., salts containing pharmaceutically acceptable anions, such as the hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate or bisulfate, phosphate or acid phosphate, acetate, lactate, citrate or acid citrate, tartrate or bi-tartrate, succinate, maleate, fumarate, gluconate, saccharate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate (i.e., 1,1′-methylene-bis-(2-hydroxy-3-naphthoate))salts.
[0835] The present invention also includes isotopically labelled compounds, which are identical to those recited in formulas I-XIB, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated into compounds of the present invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine and chlorine, such as 2 H, 3 H, 13 C, 11 C, 14 C, 15 N, 18 O, 17 O, 31 P, 32 P, 35 S, 18 F, and 36 Cl, respectively. Compounds of the present invention, prodrugs thereof, and pharmaceutically acceptable salts of said compounds or of said prodrugs which contain the aforementioned isotopes and/or other isotopes of other atoms are within the scope of this invention. Certain isotopically labelled compounds of the present invention, for example those into which radioactive isotopes such as 3 H and 14 C are incorporated, are useful in drug and/or substrate tissue distribution assays. Tritiated, i.e., 3 H, and carbon-14, i.e., 14 C, isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavier isotopes such as deuterium, i.e., 2 H, can afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements and, hence, may be preferred in some circumstances.
DETAILED DESCRIPTION OF THE INVENTION
[0836] The degree of binding to the α2δ subunit can be determined using the radioligand binding assay using [3H]gabapentin and the α2δ subunit derived from porcine brain tissue, as described by N. S. Gee et al., J. Biol. Chem., 1996, 271:5879-5776.
[0837] All that is required to practice the method of this invention is to administer an alpha2delta ligand, or a pharmaceutically acceptable salt thereof, in an amount that is therapeutically effective to treat one or more of the disorders or conditions referred to above. Such therapeutically effective amount will generally be from about 1 to about 300 mg/kg of subject body weight. Typical doses will be from about 10 to about 5000 mg/day for an adult subject of normal weight. In a clinical setting, regulatory agencies such as, for example, the Food and Drug Administration (“FDA”) in the U.S. may require a particular therapeutically effective amount.
[0838] In determining what constitutes an effective amount or a therapeutically effective amount of an alpha2delta ligand, or a pharmaceutically acceptable salt thereof, for treating onr or more of the disorders or conditions referred to above according to the invention method, a number of factors will generally be considered by the medical practitioner or veterinarian in view of the experience of the medical practitioner or veterinarian, published clinical studies, the subject's age, sex, weight and general condition, as well as the type and extent of the disorder or condition being treated, and the use of other medications, if any, by the subject. As such, the administered dose may fall within the ranges or concentrations recited above, or may vary outside, i.e., either below or above, those ranges depending upon the requirements of the individual subject, the severity of the condition being treated, and the particular therapeutic formulation being employed. Determination of a proper dose for a particular situation is within the skill of the medical or veterinary arts. Generally, treatment may be initiated using smaller dosages of the alpha2delta ligand that are less than optimum for a particular subject. Thereafter, the dosage can be increased by small increments until the optimum effect under the circumstance is reached. For convenience, the total daily dosage may be divided and administered in portions during the day, if desired.
[0839] Pharmaceutical compositions of an alpha2delta ligand, or a pharmaceutically acceptable salt thereof, are produced by formulating the active compound in dosage unit form with a pharmaceutical carrier. Some examples of dosage unit forms are tablets, capsules, pills, powders, aqueous and nonaqueous oral solutions and suspensions, and parenteral solutions packaged in containers containing either one or some larger number of dosage units and capable of being subdivided into individual doses.
[0840] Some examples of suitable pharmaceutical carriers, including pharmaceutical diluents, are gelatin capsules; sugars such as lactose and sucrose; starches such as corn starch and potato starch; cellulose derivatives such as sodium carboxymethyl cellulose, ethyl cellulose, methyl cellulose, and cellulose acetate phthalate; gelatin; talc; stearic acid; magnesium stearate; vegetable oils such as peanut oil, cottonseed oil, sesame oil, olive oil, corn oil, and oil of theobroma; propylene glycol, glycerin; sorbitol; polyethylene glycol; water; agar; alginic acid; isotonic saline, and phosphate buffer solutions; as well as other compatible substances normally used in pharmaceutical formulations.
[0841] The compositions to be employed in the invention can also contain other components such as coloring agents, flavoring agents, and/or preservatives. These materials, if present, are usually used in relatively small amounts. The compositions can, if desired, also contain other therapeutic agents commonly employed to treat the disorder or condition being treated.
[0842] The percentage of the active ingredients in the foregoing compositions can be varied within wide limits, but for practical purposes it is preferably present in a concentration of at least 10% in a solid composition and at least 2% in a primary liquid composition. The most satisfactory compositions are those in which a much higher proportion of the active ingredient is present, for example, up to about 95%.
[0843] Preferred routes of administration of an alpha2delta ligand, or a pharmaceutically acceptable salt thereof, are oral or parenteral. For example, a useful intravenous dose is between 5 and 50 mg, and a useful oral dosage is between 20 and 800 mg.
[0844] The alpha2delta ligand, or a pharmaceutically acceptable salt thereof, may be administered in any form. Preferably, administration is in unit dosage form. A unit dosage form of the alpha2delta ligand, or a pharmaceutically acceptable salt thereof, to be used in this invention may also comprise other compounds useful in the therapy of the disorder or condition for which the alpha2delta ligand is being administered or a disorder or condition that is secondary to the disorder or treatment for which the alpha2delta ligand is being administered.
[0845] Some of the compounds utilized in a method of the present invention are capable of further forming pharmaceutically acceptable salts, including, but not limited to, acid addition and/or base salts. The acid addition salts are formed from basic compounds, whereas the base addition salts are formed from acidic compounds. All of these forms are within the scope of the compounds useful in the method of the present invention.
[0846] Pharmaceutically acceptable acid addition salts of the basic compounds useful in the method of the present invention include nontoxic salts derived from inorganic acids such as hydrochloric, nitric, phosphoric, sulfuric, hydrobromic, hydroiodic, hydrofluoric, phosphorous, and the like, as well nontoxic salts derived from organic acids, such as aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxy alkanoic acids, alkanedioic acids, aromatic acids, aliphatic and aromatic sulfonic acids, etc. Such salts thus include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, trifluoroacetate, propionate, caprylate, isobutyrate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, mandelate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, phthalate, benzenesulfonate, toluenesulfonate, phenylacetate, citrate, lactate, malate, tartrate, methanesulfonate, and the like. Also contemplated are salts of amino acids such as arginate and the like and gluconate, galacturonate (see, for example, Berge S. M. et al., “Pharmaceutical Salts,” J. of Pharma. Sci., 1977;66:1).
[0847] An acid addition salt of a basic compound useful in the method of the present invention is prepared by contacting the free base form of the compound with a sufficient amount of a desired acid to produce a nontoxic salt in the conventional manner. The free base form of the compound may be regenerated by contacting the acid addition salt so formed with a base, and isolating the free base form of the compound in the conventional manner. The free base forms of compounds prepared according to a process of the present invention differ from their respective acid addition salt forms somewhat in certain physical properties such as solubility, crystal structure, hygroscopicity, and the like, but otherwise free base forms of the compounds and their respective acid addition salt forms are equivalent for purposes of the present invention.
[0848] A pharmaceutically acceptable base addition salt of an acidic compound useful in the method of the present invention may be prepared by contacting the free acid form of the compound with a nontoxic metal cation such as an alkali or alkaline earth metal cation, or an amine, especially an organic amine. Examples of suitable metal cations include sodium cation (Na + ), potassium cation (K + ), magnesium cation (Mg 2+ ), calcium cation (Ca 2+ ), and the like. Examples of suitable amines are N,N′-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, dicyclohexylamine, ethylenediamine, N-methylglucamine, and procaine (see, for example, Berge, supra., 1977).
[0849] A base addition salt of an acidic compound useful in the method of the present invention may be prepared by contacting the free acid form of the compound with a sufficient amount of a desired base to produce the salt in the conventional manner. The free acid form of the compound may be regenerated by contacting the salt form so formed with an acid, and isolating the free acid of the compound in the conventional manner. The free acid forms of the compounds useful in the method of the present invention differ from their respective salt forms somewhat in certain physical properties such as solubility, crystal structure, hygroscopicity, and the like, but otherwise the salts are equivalent to their respective free acid for purposes of the present invention.
[0850] Certain of the compounds useful in the method of the present invention can exist in unsolvated forms as well as solvated forms, including hydrated forms. In general, the solvated forms, including hydrated forms, are equivalent to unsolvated forms and are intended to be encompassed within the scope of the present invention.
[0851] Certain of the compounds useful in the method of the present invention possess one or more chiral centers, and each center may exist in the R or S configuration. A method of the present invention may utilize any diastereomeric, enantiomeric, or epimeric form of an alpha2delta ligand, or a pharmaceutically acceptable salt thereof, as well as mixtures thereof.
[0852] Additionally, certain compounds useful in the method of the present invention may exist as geometric isomers such as the entgegen (E) and zusammen (Z) isomers of alkenyl groups. A method of the present invention may utilize any cis, trans, syn, anti, entgegen (E), or zusammen (Z) isomer of an alpha2delta ligand, or a pharmaceutically acceptable salt thereof, as well as mixtures thereof.
[0853] Certain compounds useful in the method of the present invention can exist as two or more tautomeric forms. Tautomeric forms of the compounds may interchange, for example, via enolization/de-enolization and the like. A method of the present invention may utilize any tautomeric form of an alpha2delta ligand, or a pharmaceutically acceptable salt thereof, as well as mixtures thereof.
[0854] The following examples illustrate the invention pharmaceutical compositions containing an alpha2delta ligand, and a pharmaceutically acceptable carrier, diluent, or excipient. The examples are representative only, and are not to be construed as limiting the invention in any respect.
FORMULATION EXAMPLE 1
[0855] Tablet Formulation:
Amount Ingredient (mg) 3-(1-aminomethyl-cyclohexylmethyl)-4H- 25 [1,2,4]oxadiazol-5-one hydrochloride Lactose 50 Cornstarch (for mix) 10 Cornstarch (paste) 10 Magnesium stearate (1%) 5 Total 100
[0856] 3-(1-Aminomethyl-cyclohexylmethyl)-4H-[1,2,4]oxadiazol-5-one hydrochloride, lactose, and cornstarch (for mix) are blended to uniformity. The cornstarch (for paste) is suspended in 200 mL of water and heated with stirring to form a paste. The paste is used to granulate the mixed powders. The wet granules are passed through a No. 8 hand screen and dried at 80° C. The dry granules are lubricated with the 1% magnesium stearate and pressed into a tablet. Such tablets can be administered to a human from one to four times a day for treatment of ADHD.
FORMULATION EXAMPLE 2
[0000] Coated Tablets:
[0857] The tablets of Formulation Example 1 are coated in a customary manner with a coating of sucrose, potato starch, talc, tragacanth, and colorant.
FORMULATION EXAMPLE 3
[0000] Injection Vials:
[0858] The pH of a solution of 500 g of gabapentin and 5 g of disodium hydrogen phosphate is adjusted to pH 6.5 in 3 L of double-distilled water using 2 M hydrochloric acid. The solution is sterile filtered, and the filtrate is filled into injection vials, lyophilized under sterile conditions, and aseptically sealed. Each injection vial contains 25 mg of gabapentin.
FORMULATION EXAMPLE 4
[0000] Suppositories:
[0859] A mixture of 25 g of (1α,3α,5═)(3-aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid hydrochloride, 100 g of soya lecithin, and 1400 g of cocoa butter is fused, poured into molds, and allowed to cool. Each suppository contains 25 mg of (1α,3α,5α)(3-aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid hydrochloride.
FORMULATION EXAMPLE 5
[0000] Solution:
[0860] A solution is prepared from 1 g of 3-(2-aminomethyl-4-methyl-pentyl)-4H-[1,2,4]-oxadiazol-5-one hydrochloride, 9.38 g of NaH 2 PO 4 .12H 2 O, 28.48 g of Na 2 HPO 4 .12H 2 O, and 0.1 g benzalkonium chloride in 940 mL of double-distilled water. The pH of the solution is adjusted to pH 6.8 using 2 M hydrochloric acid. The solution is diluted to 1.0 L with double-distilled water, and sterilized by irradiation. A 25 mL volume of the solution contains 25 mg of 3-(2-aminomethyl-4-methyl-pentyl)-4H-[1,2,4]-oxadiazol-5-one hydrochloride.
FORMULATION EXAMPLE 6
[0000] Ointment:
[0861] 500 mg of 3-(1-aminomethyl-cycloheptylmethyl)-4H-[1,2,4]oxadiazol-5-one hydrochloride is mixed with 99.5 g of petroleum jelly under aseptic conditions. A 5 g portion of the ointment contains 25 mg of 3-(1-aminomethyl-cycloheptylmethyl)-4H-[1,2,4]oxadiazol-5-one hydrochloride.
FORMULATION EXAMPLE 7
[0000] Capsules:
[0862] 2 kg of 3-(1-aminomethyl-cyclohexylmethyl)-4H-[1,2,4]oxadiazol-5-one hydrochloride are filled into hard gelatin capsules in a customary manner such that each capsule contains 25 mg of 3-(1-aminomethyl-cyclohexylmethyl)-4H-[1,2,4]oxadiazol-5-one hydrochloride.
FORMULATION EXAMPLE 8
[0000] Ampoules:
[0863] A solution of 2.5 kg of gabapentin is dissolved in 60 L of double-distilled water. The solution is sterile filtered, and the filtrate is filled into ampoules. The ampoules are lyophilized under sterile conditions and aseptically sealed. Each ampoule contains 25 mg of gabapentin.
[0864] Having described the invention method, various embodiments of the invention are hereupon claimed. | The invention relates to a method of treating central nervous system disorders and other disorders by administering an alpha2delta ligand such as, for example, a compound of the formula
or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen or straight or branched lower alkyl, and n is an integer of from 4 to 6. | 0 |
BACKGROUND OF THE INVENTION
The invention set forth in this specification pertains to new and improved game structures. The embodiment of the invention specifically disclosed in this specification pertains to a game structure which simulates to a degree the game of basketball. It is considered, however, that the principles of the invention can be utilized to provide a series of different game structures which simulate to various extents any of a series of games in which a member such as a ball, a shuttlecock or the like is moved or propelled from one extremity of a playing area to another.
It will, of course, be recognized that an untold number of different game structures capable of being utilized to simulate games as are noted in the preceding have been developed and utilized in the past. Within a comparatively recent time period a number of different electronic games have been developed which are based upon the movement of a dot of light simulating a ball or other member being propelled back and forth across the viewing surface of a cathode ray tube. Such games are normally played by one or more players adjusting a member with respect to the moving dot of light so as to intercept and cause the dot of light to move back and forth along the playing surface.
Games of the latter category have extensively caught the imagination of the public. They are considered to be highly effective as game structures. It is also considered that such game structures are, because of their electronic character, sufficiently high priced so that they cannot be widely utilized and accepted, particularly by children. Many children know of such electronic games and desire to utilize them.
BRIEF SUMMARY OF THE INVENTION
As a result of the latter it is considered that there is a need for new and improved game structures which effectively simulate electronic games as are indicated in the preceding discussion, but which are of such a character that they are much less expensive than such electronic games. A broad objective of the present invention is to fulfill this need. Related objectives of this invention are to provide game structures which simulate electronic games in which a dot of light moves back and forth across the surface of a cathode ray tube which are comparatively simple to construct, which are comparatively inexpensive, which are essentially mechanical in character, which are capable of prolonged use by children without mechanical breakdown, and which are very effective for play purposes in holding the attention of children.
In accordance with this invention these various objectives are achieved by providing a game structure which comprises: a housing having a bottom, a transluscent or transparent front surface, and ends connected by the bottom and the front surface, a carriage movably mounted on the bottom so as to be capable of being moved back and forth along a path in back of the front surface, visible means for simulating a member which is moved as the game is played supported on the carriage so as to be moved as the carriage is moved, this visible means being capable of being viewed through the front surface, and at least one moving means for moving the carriage, the moving means being capable of being actuated so as to exert repetitive blows against the carriage in order to move the carriage.
BRIEF DESCRIPTION OF THE DRAWINGS
A game structure of the present invention is preferably somewhat more complex than indicated in the preceding summary so as to be capable of effectively simulating a known game in which a member is moved back and forth as the game is played such as basketball. Because of this it is considered that the invention is best more fully described with reference to the accompanying drawings in which:
FIG. 1 is a front elevational view of a presently preferred embodiment or form of a game structure of the present invention constructed so as to simulate the game of basketball;
FIG. 2 is a rear elevational view of this game structure;
FIG. 3 is a rear elevational view with the rear cover of the game removed, this view being partially broken away so as to facilitate an understanding of the invention;
FIG. 4 is a cross sectional view taken at line 4--4 of FIG. 3;
FIG. 5 is a partial cross sectional view taken at line 5--5 of FIG. 3;
FIG. 6 is a front elevational view of part of an arm employed in the structure illustrated in the preceding figures showing a light source employed as a visible means simulating a basketball;
FIG. 7 is a partial isometric view indicating the principal parts of a striker structure or moving means employed in the game illustrated in the preceding figures for moving a carriage; and
FIG. 8 is an isometric view of an actuator serving as an escapement lever in a counting structure or counting means employed in the game structure illustrated.
The particular game structure illustrated embodies certain operative concepts or principles as are set forth in the various claims at the end of this specification. Those familiar with the design and construction of mechanical toys will realize that these concepts or principles can be easily embodied within a wide variety of differently constructed and differently appearing game structures through the use or exercise of routine skill in the field of the design and construction of mechanical toys.
DETAILED DESCRIPTION
The toy game structure 10 of the invention illustrated includes a housing 12 formed so as to include a transluscent or transparent front surface 14, a bottom or base 16, opposed ends 18 connected by the surface 14 and the bottom 16, a top 20 and a removable back cover 22 serving to enclose various operative parts as hereinafter indicated. Indicia 24 simulating a basketball court and further indicia 26 simulating the baskets used with such a court are provided on the front surface 14.
A support platform 28 forming part of the bottom or base 16 is located within the housing 12 intermediate the ends 18. This platform 28 includes an elongated slot 30 extending parallel to the front surface 14. Rubber bumpers 32 are mounted on the platform 28 in alignment with the slot 30 and spaced from the ends 34 of the slot 30. This platform 28 is used to support a carriage 36 having wheels 38 which rest upon the platform 28. A small guide member 40 extends downwardly from the carriage 36 through the slot 30 for the purpose of insuring that the carriage 36 will only move in a linear path parallel to the front surface 14.
Preferably an enlarged head 42 is provided on the guide 40 for the purpose of preventing movement of the carriage 36 generally away from the platform 28. With this structure the bumpers 32 limit the movement of the carriage 36 toward the ends 18 of the housing 12. These bumpers 32 are preferably formed of an elastomeric material such as a rubber composition so as to absorb any shock resulting from the carriage 36 hitting against them so as to minimize vibration.
The carriage 36 is provided with parallel, upstanding, spaced supports 44. Each of these supports 44 is provided with an upwardly directed groove serving as a bearing opening 46. If desired one of these supports 44 may include a small, pivotally mounted shaft retainer 48 which frictionally bears against the support 44 upon which it is located. These bearing openings 46 support a shaft 50 extending from both sides of a light unit 52. The retainer 48 is adapted to be utilized to hold the shaft 50 so as to prevent the light unit 52 from moving away from the carriage 36.
This light unit 52 includes a bottom section 54 serving as a housing holding batteries 56. This bottom section 54 preferably also includes a small counter weight 58 tending to balance the entire light unit 52 so that it may be pivotted between positions in which an arm 60 extending from the bottom section 54 is directed generally toward either of the ends 18. The arm 60 carries a small housing 62 carrying a light bulb (and socket) 64 remote from the shaft 50. An opening 66 in the housing 62 is used to convey light from the bulb 64 to immediately in back of the front surface 14 so that the light from the bulb 64 will be visible through this front surface 14.
Preferably this front surface 14 will be transluscent so that the light from the bulb 64 will be visible through the front surface 14 while various other operative parts within the housing 12 are concealed from view. It is, however, possible to form an effective game structure 10 in which the front surface 14 is transparent. The important factor is to make the game structure 10 in such a manner that this light bulb 64 or any other equivalent element substituted for it such as a colored disk (not shown) is visible through the front surface 14 as the game structure 10 is used.
This opening 66 is preferably formed as indicated in FIG. 6 so as to have various internal ribs 68 effectively simulating the stitching on a common ball such as a basketball. The light unit 52 also includes various conventional conductors 70 and a conventional switch 72 mounted on the bottom section 54 and on the arm 60 for the purpose of controlling the operation of the bulb 64. A small door 74 of conventional design may be provided on the back cover 22 for the purpose of facilitating access to the switch 72.
The carriage 36 also includes two separate levers 76 each of which is pivotally mounted on the carriage 36 through the use of conventional fasteners 78 serving as pivots. Lugs 80 on the carriage 36 limit the downward movement of these levers 76 and the retainer 48 limits the upward movement of the levers 76 in such a manner that these levers 76 will always tend to fall back against the lugs 80 after they have been engaged. These levers 76 are located adjacent to a plate 82 which is mounted within the housing 12 parallel to the front surface 14 immediately above the bottom 16 within the back cover 22.
This plate 82 is formed so as to include two identical ramps 84 located adjacent to slots 86 which extend parallel to these ramps 84. Each of the ramps 84 leads upwardly at an angle from adjacent to an end 18. Each of the ramps 84 terminates at a stop 88 formed in the plate 82. These ramps 84 are adapted to carry what are referred to herein as strikers 90. These strikers 90 are mirror images of one another. Each of these strikers 90 includes a body portion 92 carrying a shaft 94 mounting a comparatively heavy roller 96. It will be noted that these body portions 92 include enlarged sides 98 which effectively straddle the ramps 84 so as to serve to guide the strikers 90 so that they will only move in a linear manner along the ramps 84.
The rollers 96 employed are sufficiently heavy so as to be capable of returning the strikers 90 through the action of gravity toward positions as shown in FIG. 3 in which these strikers 90 are at the lowermost portions (not separately numbered) of the ramp 84 adjacent to the end 18. Each of the body portions 92 includes a hammer-like end 100 which is adapted to engage one of the levers 76 in order to impart motion to the carriage 36. It will be realized that when a lever 76 is engaged by a hammer-like end 100 of a striker 90 that this lever 76 will be rotated slightly in an amount depending upon the degree of the impact by the hammer-like end 100. The initial rotation of a lever 76 will not normally result in movement of the carriage 36. If the force applied by a hammer-like end 100 is great enough a lever 76 will be moved into engagement with the shaft retainer 48 and this in turn will cause movement of the carriage 36.
An important feature of the present invention which is considered to aid in the game structure 10 effectively simulating the game of basketball relates to the fact that the light unit 52 includes a shock absorbing rubber projection 102 which extends outwardly from the remainder of this unit 52 to a sufficient extent so as to be capable of engaging a sloping surface 104 on either of the levers 76 when the light unit 52 is in either of the two substantially horizontal positions that this unit 52 can assume. With this type of structure when the projection 102 is at rest against a sloping surface 104 of a lever 76 and when this lever 76 is engaged by the hammer-like end 100 of the striker 90 the movement of the lever 76 which is so engaged by the striker 90 will result in pivotting of the light unit 52 relative to the carriage 36. Thus, this rotation of the light unit 52 is in a sense independent of the movement of the carriage 36 although the light unit 52 is supported on the carriage 36 so as to be capable of being moved as the carriage 36 is moved.
Bell crank type levers 106 which are mirror images of one another are mounted upon shafts 108 so that arms 110 of these levers 106 project outwardly through openings 112 in the ends 18. These arms 110 are preferably shaped much as handles so that they may be manually engaged so as to be rotated against stops 114 located on the ends 18. During such rotation internal arms 116 on these levers 106 will hit against the strikers 90 when such strikers 90 happen to be at or adjacent to the end (not separately numbered) of a ramp 84 adjacent to an end 18. The impact of an arm 116 with a striker 90 is intended to propel such a striker 90 so as to impart movement to the carriage 36 and the light unit 52 in the manner described in the preceding. Because of their function the striker 90, the ramp 84 and the lever 106 may be collectively referred to as a moving means.
Such movement as is caused by appropriate actuation of the levers 106 so that repetitive blows are delivered to the strikers 90 through the actuation of the levers 106 will cause the carriage 36 to move back and forth along a linear path parallel to the front surface 14. Concurrently the light unit 52 will pivot back and forth relative to the carriage 36 and the front surface 14. As this occurs the light emitted from the bulb 64 will on occasion pass adjacent to the areas (not separately numbered) on the front surface 14 containing indicia 26 simulating baskets. This will, of course, correspond to "baskets" being made in a conventional game of basketball.
In order to improve playability of the game structure 10 it is considered desirable to incorporate within this game structure 10 two counters 118 which will count the number of "baskets" made during the use of the game structure 10. Each of these counters 118 includes an assembly (not separately numbered) of a framework 120 carrying a rotatable drum 122 located about a shaft 124. The shafts 124 are mounted on the frameworks 120 so as to extend to the front surface 14 adjacent to the bottom 16. There small hands 126 are located on the shafts 124 so as to point to dials 128 containing numbers. The shafts 124 are also secured to conventional crown ratchet wheels 130 which are intended to be utilized in controlling the rotation of the shafts 124 and the drums 122.
Elongated actuators 132 are pivotally mounted by pins 134 on the frameworks 120 so that the lowermost ends 136 of these actuators 132 are adjacent to the ratchet wheels 130. Conventional escapement teeth 138 are provided on the actuators 132 so as to coact with the ratchet wheels 130 in order to permit a limited amount of rotation of each shaft 124 each time a corresponding actuator 132 is deflected so as to bring its end 136 generally toward a ratchet wheel 130.
Small coil springs 140 extending between the drums 122 and the framework 120 will normally tend to bias the ratchet wheels 130 so that they are held against rotation by escapement teeth 138 and so that during each movement of an end 136 toward the ratchet wheel 130 there will be restricted motion of a shaft 124. The springs 140 can, of course, be placed under tension by rotating the hands 126 so as to reset the counters 118. The teeth (not separately numbered) of the ratchet wheels 130 slide against the escapement teeth 138 in order to permit such resetting of the counters 118.
Each of the actuators 132 is supplied with a tapered surface 142 which is adapted to be engaged by the arm 60 as the light unit 52 is moved and rotated so as to pass adjacent to the basket indicia 26. Such engagement of its tapered surface 142 will cause an actuator 132 to be pivotted in order to permit the end 136 to be moved so that the escapement teeth 138 coact with the ratchet wheel 130 in order to permit limited movement of a hand 126 and a counter 118. Small coil springs 144 are normally connected between the actuators 132 and the framework 120 for the purpose of biasing these actuators 132 in positions in which the escapement teeth 138 prevent rotation of the ratchet wheels 130 and in positions in which the surfaces 142 are located so that they can be engaged by the arm 60. If desired, however, these springs 144 may be dispensed with when the actuators 132 are balanced so as to automatically pivot back to a "normal" position through the action of gravity.
The actuators 132 also include stop walls 146 located at the lowermost extremities of the tapered surfaces 142. These stop walls 146 are designed to prevent the resilience of the projection 102 from causing the light unit 52 to bounce back away from a substantially horizontal position after a "basket" has been made as indicated by the light unit 52 passing relative to an indicia 26 as indicated. The action of a spring 144 will automatically return an actuator 132 to a position in which the light unit 52 cannot be pivotted relative to the carriage 36 until such time as one of the strikers 90 moves so as to cause movement of the carriage 36 to a sufficient extent so that a stop wall 146 will no longer preclude rotation of the light unit 52 relative to the carriage 36.
It is believed that it will be apparent from the preceding that the game structure 10 is of such a character that it can be manufactured without significant difficulty at a comparatively nominal cost. This game structure 10 is of a comparatively simple mechanical character which contributes to the game structure 10 being capable of prolonged use by children without mechanical malfunction. There are obviously a number of ways that the particular game structure 10 can be modified. The particular game structure 10 is primarily designed or intended for use by two children. It is considered that an effective toy or game may be manufactured utilizing the principles of this invention so that only one of the moving means for moving the carriage 36 are employed. Such a modified unit would substantially correspond to an individual shooting baskets by himself or herself. | A game structure capable of being used to simulate to a degree any of a series of games such as basketball, volleyball or the like can be constructed so as to utilize a housing having a transluscent or transparent front surface. In a game structure as disclosed a carriage is mounted in the housing in back of the front surface so as to be capable of being moved back and forth along a path. A member simulating a member which is moved as a game is played is supported on the carriage so as to be moved as the carriage is moved. This member is of such a character as to be capable of being viewed through the front surface of the housing. Two separate structures are provided for moving the carriage. One of these is mounted adjacent to one end of the housing and the other is mounted adjacent to the other end of the housing. Each of these structures for moving the carriage is capable of being actuated so as to exert repetitive blows against the carriage as it is repetitively actuated in order to cause the carriage to move. | 0 |
CROSS-REFERENCE TO RELATED APPLICATIONS
A previously filed co-pending commonly assigned application related this application is Ser. No. 08/454,975 filed May 31, 1995 by Joseph E. Scheffelin et al. (the "'975 application") entitled CONTINUOUS REFILL OF SPRING BAG RESERVOIR IN AN INK-JET SWATH PRINTER/PLOTTER, which is incorporated herein by reference.
Other more recent co-pending commonly assigned related applications are application Ser. No. 08/726,587, filed Oct. 7, 1996, entitled INKJET CARTRIDGE FILL PORT ADAPTOR, by Max S. Gunther, et al. now U.S. Pat. No. 5,874,976; application Ser. No. 08/805,859, filed Mar. 3, 1997, entitled REPLACEABLE INK SUPPLY MODULE (BAG/BOX/TUBE/VALVE) FOR REPLENISHMENT OF ON-CARRIAGE INKJET PRINTHEAD, by E. Zapata et al.; application Ser. No. 08/805,860, filed Mar. 3, 1997, entitled SPACE-EFFICIENT ENCLOSURE SHAPE FOR NESTING TOGETHER A PLURALITY OF REPLACEABLE INK SUPPLY BAGS, by E. Coiner, et al.; application Ser. No. 08/910,840, filed Mar. 3, 1997, entitled PRINTING SYSTEM WITH SINGLE ON/OFF CONTROL VALVE FOR PERIODIC INK REPLENISHMENT OF INKJET PRINTHEAD, by M. Gunther et al. now U.S. Pat. No. 5,929,883; application Ser. No. 08/805,861, filed Mar. 3, 1997, entitled PRINTER APPARATUS FOR PERIODIC AUTOMATED CONNECTION OF INK SUPPLY VALVES WITH MULTIPLE INKJET PRINTHEADS, by Olazabal et al.; and application Ser. No. 08/806,749, filed Mar. 3, 1997, entitled VARIABLE PRESSURE CONTROL FOR INK REPLENISHMENT, by M. Young et al. now U.S. Pat. No. 5,992,985.
This invention relates to ink-jet printers/plotters, and more particularly to techniques in varying off-axis ink cartridge reservoir height to decrease on-carriage print cartridge refill time, ensure ink refill volume reliability and set print cartridge vacuum pressure.
BACKGROUND OF THE INVENTION
A printing system is described in the commonly assigned patent application entitled "CONTINUOUS REFILL OF SPRING BAG RESERVOIR IN AN INK-JET SWATH PRINTER/PLOTTER" which employs off-carriage ink reservoirs connected to on-carriage print cartridges through flexible tubing. The off-carriage reservoirs continuously replenish the supply of ink in the internal reservoirs of the on-carriage print cartridges, and maintain the back pressure in a range which results in high print quality. While this system has many advantages, there are some applications in which the relatively permanent connection of the off-carriage and on-carriage reservoirs via tubing is undesirable.
A new ink delivery system (IDS) for printer/plotters has been developed, wherein the on-carriage spring reservoir of the print cartridge is only intermittently connected to the off-carriage reservoir to "take a gulp" and is then disconnected from the off-carriage reservoir. No tubing permanently connecting the on-carriage and off-carriage elements is needed. The above-referenced applications describe certain features of this new ink delivery system.
BRIEF SUMMARY OF THE INVENTION
This invention optimizes the performance of this new off-carriage, take-a-gulp ink delivery system. In this type of IDS, a pen cartridge that uses an internal spring to provide vacuum pressure is intermittently connected to an ink reservoir located off the scanning carriage axis. Starting with a "full" pen cartridge, the printer will print a variety of plots while monitoring the amount of ink used. After a specified amount of ink has been dispensed, the pen carriage is moved to a refill station for ink replenishment. In the refill station, a valve is engaged into the pen, thus connecting the ink reservoir to pen cartridge and opening a path for ink to flow freely. Using only the vacuum pressure present in the pen cartridge, ink is "pulled" into the pen from the reservoir.
An inkjet printing system having a replaceable set of ink-related components which are installed together and replaced together as a single ink delivery system for each different color of ink. The set includes an ink printhead with an inlet port, an ink supply module, and a printhead service module, each of which is manually mountable by a user onto an inkjet printer. The ink supply module contains enough ink to completely replenish an entire printhead reservoir several times before the expected useful life of the printhead has expired, at which time a user can replace the entire set of ink-related components for a particular color. Similarly, the printhead service module is designed for reliable performance for the expected useful life of the printhead. This system enables the entire ink delivery system to be replaced for different printing needs, such as replacing indoor dye-based inks with outdoor pigment based inks.
BRIEF DESCRIPTION OF THE DRAWING
These and other features and advantages of the present invention will become more apparent from the following detailed description of an exemplary embodiment thereof, as illustrated in the accompanying drawings, in which:
FIG. 1 is an isometric view of a large format printer/plotter system employing the invention.
FIG. 2 is an enlarged view of a portion of the system of FIG. 1, showing the refill station.
FIG. 3 is a top view showing the printer carriage and refill station.
FIG. 4 is an isometric view of an ink-jet print cartridge usable in the system of FIG. 1, with a refill platform housing portion, a needle valve, and supply tube in exploded view.
FIG. 5 is a cross-sectional view taken along line 5--5 of FIG. 4, showing the valve structure in a disengaged position relative to a refill port on the print cartridge.
FIG. 6 is a cross-sectional view similar to FIG. 5, but showing the valve structure in an engaged position relative to the refill port of the print cartridge.
FIG. 7 is a cross-sectional view taken along line 7--7 of FIG. 6 and showing structure of the needle valve and locking structure for locking the valve in the refill socket at the refill station.
FIG. 8 is a cross-sectional view similar to FIG. 7, showing the lock in a released position.
FIG. 9 is an enlarged view showing the mechanism for moving the valve structure, without any valves mounted thereon.
FIG. 10 shows an off-carriage ink supply module incorporating the present invention.
FIG. 11 is a schematic representation showing a plurality of off-carriage ink supply modules connected to the valve structure.
FIG. 12 is a detailed side view showing the mechanism for moving the valve structure in disengaged position with a print cartridge.
FIG. 13 is a detailed side view showing the mechanism for moving the valve structure in engaged position with a print cartridge.
FIGS. 14A and 14B show an isometric and a side view, respectively of a service station module incorporating the present invention.
FIG. 15 is an isometric view of a carriage for removably mounting the service station module of FIGS. 14A-14B.
FIG. 16 is an isometric view of a carriage moving across a print zone.
FIG. 17 shows the carriage of FIG. 16 in position at the refill station, with the valve structure in disengaged positon.
FIGS. 18A and 18B show the printer with the refill station and service station doors in closed and open positions, respectively.
FIG. 19 is an exploded schematic view showing the integrated ink delivery system component of the invention (print cartridge, ink supply module and service station module) incorporated into a single package.
FIG. 20 shows six exemplary steps for replacing the print cartridge of the present invention.
FIG. 21 shows five exemplary steps for replacing the ink supply module of the present invention.
FIG. 22 shows five exemplary steps for replacing the service station module of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
An exemplary application for the invention is in a swath plotter/printer for large format printing (LFP) applications. FIG. 1 is a perspective view of a thermal ink-jet large format printer/plotter 50. The printer/plotter 50 includes a housing 52 mounted on a stand 54 with left and right covers 56 and 58. A carriage assembly 60 is adapted for reciprocal motion along a carriage bar, shown in phantom under cover 58. A print medium such as paper is positioned along a vertical or media axis by a media axis drive mechanism (not shown). As is common in the art, the media drive axis is denoted as the `x` axis and the carriage scan axis is denoted as the `y` axis.
FIG. 3 is a top view diagrammatic depiction of the carriage assembly 60, and the refill station. The carriage assembly 60 slides on slider rods 94A, 94B. The position of the carriage assembly 60 along a horizontal or carriage scan axis is determined by a carriage positioning mechanism with respect to an encoder strip 92. The carriage positioning mechanism includes a carriage position motor 404 (FIG. 15) which drives a belt 96 attached to the carriage assembly. The position of the carriage assembly along the scan axis is determined precisely by the use of the encoder strip. An optical encoder 406 (FIG. 15) is disposed on the carriage assembly and provides carriage position signals which are utilized to achieve optimal image registration and precise carriage positioning. Additional details of a suitable carriage positioning apparatus are given in the above-referenced '975 application.
The printer 50 has four ink-jet print cartridges 70, 72, 74, and 76 that store ink of different colors, e.g., black, yellow, magenta and cyan ink, respectively, in internal spring-bag reservoirs. As the carriage assembly 60 translates relative to the medium along the y axis, selected nozzles in the ink-jet cartridges are activated and ink is applied to the medium.
The carriage assembly 60 positions the print cartridges 70-76, and holds the circuitry required for interface to the heater circuits in the cartridges. The carriage assembly includes a carriage 62 adapted for the reciprocal motion on the front and rear sliders 92A, 92B. The cartridges are secured in a closely packed arrangement, and may each be selectively removed from the carriage for replacement with a fresh pen. The carriage includes a pair of opposed side walls, and spaced short interior walls, which define cartridge compartments. The carriage walls are fabricated of a rigid engineering plastic. The print heads of the cartridges are exposed through openings in the cartridge compartments facing the print medium.
As mentioned above, full color printing and plotting requires that the colors from the individual cartridges be applied to the media. This causes depletion of ink from the internal cartridge reservoirs. The printer 50 includes four take-a-gulp IDSs to meet the ink delivery demands of the printing system. Each IDS includes three components, an off-carriage ink reservoir, an on-carriage print cartridge, and a head cleaner. The ink reservoir includes a bag holding 350 ml of ink, with a short tube and refill valve attached. Details of a ink reservoir bag structure suitable for the purpose are given in co-pending application Ser. No. 08/805,860, filed Mar. 3, 1997, SPACE-EFFICIENT ENCLOSURE SHAPE FOR NESTING TOGETHER A PLURALITY OF REPLACEABLE INK SUPPLY BAGS, by Erich Coiner et al. These reservoirs are fitted on the left-hand side of the printer (behind the door of the left housing 58) and the valves attach to a refill arm 170, also behind the left door, as will be described below. The print cartridge in this exemplary embodiment includes a 300-nozzle, 600 dpi printhead, with an orifice through which it is refilled. The head cleaner includes a spittoon for catching ink used when servicing and calibrating the printheads, a wiper used to wipe the face of the printhead, and a cap (used to protect the printhead when it is not in use). These three components together comprise the IDS for a given color and are replaced as a set by the user.
The proper location of each component is preferably identified by color. Matching the color on the replaced component with that on the frame that accepts that component will ensure the proper location of that component. All three components will be in the same order, with, in an exemplary embodiment, the yellow component to the far left, the cyan component in the center-left position, the magenta component in the center-right position and the black component in the far-right position.
The ink delivery systems are take-a-gulp ink refill systems. The system refills all four print cartridges 70-76 simultaneously when any one of the print cartridge internal reservoir's ink volume has dropped below a threshold value. A refill sequence is initiated immediately after completion of the print that caused the print cartridge reservoir ink volume to drop below the threshold and thus a print should never be interrupted for refilling (except when doing a long-axis print that uses more than 5 ccs of ink of any color).
The '975 application describes a negative pressure, spring-bag print cartridge which is adapted for continuous refilling. FIGS. 4-8 show an ink-jet print cartridge 100, similar to the cartridges described in the '975 application, but which is adapted for intermittent refilling by addition of a self-sealing refill port in the grip handle of the cartridge. The cartridge 100 illustrates the cartridges 70-76 of the system of FIG. 1. The cartridge 100 includes a housing 102 which encloses an internal reservoir 104 for storing ink. A printhead 106 with ink-jet nozzles is mounted to the housing. The printhead receives ink from the reservoir 104 and ejects ink droplets while the cartridge scans back and forth along a print carriage during a printing operation. A protruding grip 108 extends from the housing enabling convenient installation and removal from a print carriage within an ink-jet printer. The grip is formed on an external surface of the housing.
FIGS. 5-8 show additional detail of the grip 108. The grip includes two connectors 110, 112 on opposing sides of a cylindrical port 114 which communicates with the reservoir 104. The port is sealed by a septum 116 formed of an elastomeric material. The septum 116 has a small opening 118 formed therein. The grip with its port 114 is designed to intermittently engage with a needle valve structure 120 connected via a tube 122 to an off-carriage ink reservoir such as one of the reservoirs 80-86 of the system of FIG. 1. FIG. 5 shows the valve structure 120 adjacent but not engaged with the port 116. FIG. 6 shows the valve structure 120 fully engaged with the port. As shown in FIG. 6, the structure 120 includes hollow needle 122 with a closed distal end, but with a plurality of openings 124 formed therein adjacent the end. A sliding valve collar 128 tightly fits about the needle, and is biased by a spring 126 to a valve closed position shown in FIG. 5. When the structure 120 is forced against the port 116, the collar is pressed up the length of the needle, allowing the needle tip to slid into the port opening 118, as shown in FIG. 6. In this position, ink can flow through the needle openings 124 between the reservoir 104 and the tube 130. Thus, with the cartridge 100 connected to an off-carriage ink reservoir via a valve structure such as 120, a fluid path is established between the print cartridge and the off-carriage reservoir. Ink can flow between the off-carriage ink reservoir to the cartridge reservoir 104. When the structure 120 is pulled away from the handle 108, the valve structure 120 automatically closes as a result of the spring 126 acting on the collar 128. The opening 118 will close as well due to the elasticity of the material 116, thereby providing a self-sealing refill port for the print cartridge.
FIGS. 4-8 illustrate a locking structure 127 for releasably locking the valve 120 into the refill arm 170 at socket 174. The structure 172 has locking surfaces 172B (FIG. 5) which engage against the outer housing of the valve body 120A. The structure is biased into the lock position by integral spring member 172A (FIGS. 7 and 8). By exerting force on structure 170 at point 170C (FIGS. 7 and 8) the spring is compressed, moving surface 172B out of engagement with the valve body, and permitting the valve to be pulled out of the refill arm socket 174. This releasing lock structure enables the valve and reservoir to be replaced quickly as a unit.
The print cartridges 70-76 each comprise a single chamber body that utilizes a negative pressure spring-bag ink delivery system, more particularly described in the '975 application.
In the exemplary system of FIG. 1, the refill platform 150 is in the left housing 56 of the printer 50 as shown in FIG. 2. The four off-carriage ink reservoirs 80-86 are supported on the platform 150. Short flexible tubes 150, 152, 154 and 156 connect between ports 80A-86A of corresponding reservoirs 80-86 and needle valve structure 160, 162, 164 and 166 supported at a refill station housing 170. These needle valve structures each correspond to the valve structure 120 of FIGS. 4-8.
The refill platform 150 is an elevator that holds the four reservoirs and can be moved up and down.
To perform a refill the carriage assembly 60 is moved to the refill station where the four off-carriage reservoirs 80-86 are connected to the corresponding print cartridges 70-76 via the shut-off valves 160-166. The connection of the reservoirs is accomplished by turning a stepper motor 200 that advances a lever 202 on which the valve structures and refill station housing 170 are mounted, as shown in FIGS. 3 and 12-13. A system suitable for moving the valves into and out of engagement with the refill ports is more fully described in co-pending application Ser. No. 08/805,861, filed Mar. 3, 1997, APPARATUS FOR PERIODIC AUTOMATED CONNECTION OF INK SUPPLY VALVES WITH MULTIPLE PRINTHEADS, by Ignacio Olazabal et al. While the valves are engaged in the refill ports of the print cartridges, ink is pulled into the print cartridge reservoir due to the slight vacuum pressure (back pressure) in it. This back pressure is known to decrease with increasing ink volume. This results in a self-regulating refill process where, as more ink is introduced into the print cartridge, the back pressure decreases to a point where the print cartridge can no longer pull additional ink from the cartridge and the refill stops. The pressure at which the flow of ink stops is governed by the distance offsetting the print cartridge and the off-carriage reservoir. The farther below the print cartridge the reservoir is located, the greater the final pressure in the print cartridge and the lower the resulting volume of ink in the print cartridge internal reservoir.
As best shown in FIG. 16, the present invention does not require the specifications of the carriage to be redesigned due to the drag and interference that results from typical off-carriage ink systems where ink supply tubes remain constantly connected with the cartridges on the carriage during a printing operation. In contrast, the carriage shown in the drawings can move back and forth across the print zone without any supply tube connection whatsoever. Moreover, there is no need to account for the additional carriage mass that typically results from having a replaceable supplemental ink supply mounted directly on the carriage.
Additional details of the apparatus which provides the periodic connection/disconnection at the refill station between the print cartridge fill port and the off-carriage ink supply valve will now be described. Referring to FIGS. 9, 12-13 and 17, a bracket holding the ink supply valves supports the motor 200 which turns gears 210 to move gear arms 212 back and forth between a position of engagement of the supply valves with their respective fill ports on the print cartridges, and a position of disengagement. Primary stabilizing arms 214 on the bracket as well as secondary stabilizing arms 215 on the carriage provide the necessary restraint required to minimize an undue stress on the cartridges which might otherwise displace their precise positioning in the carriage. The beginning and end points of the engagement/disengagement are defined by an optical sensor 216.
In the presently preferred embodiment of the invention, all four ink supply valves move together as a unit as they are held in fixed position in their apertures 218 by individual locking buttons 219 that allow each valve to be separately replaced whenever the expected life of the integrated IDS has expired for that particular color of ink. When replacement is required, an arrow-shaped orientation key 222 mates with a matching orientation slot 224 by easy manual manipulation through a valve handle 226.
A unique narrow replaceable service station module 230 for each color ink is an important part of the IDS. Referring to FIGS. 14A-14B and 15, this service station module includes a protruding handle 232 on one end, and a group of printhead servicing components which are combined together in a relatively small area on top of the module. At one end are dual wipers 234 and at the other a spittoon 238 with a nozzle plate cap 236 at an intermediate position. An external primer port 240 in the module is connected through an interior passage to the cap 236, and in the opposite direction through a circular seal 242 to a vacuum source. A service station carriage 251 includes separate slots 244, 246, 248, 250 for each service station module (also sometimes called a printhead cleaner).
A spring-loaded datum system provides for the service station module to be easily but precisely positioned in the service station carriage. Along a top portion of each slot is a z-datum ridge 252 which engages a corresponding datum ledge 254 along both top edges of the module. An upwardly biased spring arm 260 assures a tight fit along these datum surfaces. A horizontal positioning is provided in each slot by a pair of protruding corners which act as latches against matching stops 258 on the module. Although not required, a biasing arm 262 may be employed in a rear wall of each slot.
FIG. 10 shows the basic exterior structure of an ink supply module before installation, and FIG. 11 shows how four such modules are grouped together on a refill platform on the printer with their valves manually installed on the valve bracked.
FIGS. 18A and 18B illustrate the accessability required for replacement of the three basic components parts of the IDS. The front of the printer unit typically includes a roll feed unit 270, a control panel 272 and a print zone access door 274 adjacent an elongated frame member 275. The service station is located at the right end of the carriage scan axis, and a refill station 278 at the opposite end. Simple friction latches such as indicated at 280 are provided to assure proper closure of doors which a mounted on pivot hinges such as 281. A pusher plate 284 contacts and helps to position any incompletely mounted service station modules upon closure of a service station door 282. A similar door 286 closes off the refill station during normal operation of the printer. The refill station includes space 287 for an ink supply platform, and an access hole 288 from the platform to carriage-mounted printheads.
An installation procedure will now be described in conjunction with FIGS. 19-22. An ink delivery system is preferably packaged as a unit in a carton 290 which holds a new print cartridge 291A, a new service station module 293A in a plastic storage bag 295, and a new ink supply module 296A. As shown in the self-explanatory sequence of drawings of FIG. 20, an old print cartridge 293B is easily removed and replaced with a new one. As shown in the self-explanatory sequence of drawings of FIG. 21, a depleted ink supply module 296B is removed without difficulty by first opening the ink door as shown by arrow 302, then pushing down on the lock button as shown by arrow 304 and at the same time pulling out the valve as shown by arrow 306. The depleted ink module 296B can then be replaced with a new ink supply module 296A. Finally as shown in the self-explanatory sequence of drawings of FIG. 22, after the access door is opened a user can push down on the handle in the direction shown by arrow 310 thereby dislodging an old service station module 293B, and then pull it out all the way as indicated by arrow 312, followed by installation of a new service station module 293A.
Accordingly it will be appreciated by those skilled in the art that the basic features of the unique take-a-gulp ink replenishment system of the present invention provides a unique but relatively simple way of providing for unattended printing through automated ink replenishment. Furthermore, all ink-related components can be replaced for a particularly color of ink by a user, without the need of special tools and without the need of calling a specialized service person.
While a preferred embodiment of the invention has been shown and described, it will be appreciated by those skilled in the art that various modifications can be made without departing from the spirit and scope of the invention as defined by the following claims. | An inkjet printing system having a replaceable set of ink-related components which are installed together and replaced together as a single ink delivery system for each different color of ink. The set includes an ink printhead cartridge with an inlet port, an ink supply module, and a printhead service module, each of which is manually mountable by a user onto an inkjet printer. The ink supply module contains enough ink to completely replenish an entire printhead reservoir several times before the expected useful life of the printhead cartridge has expired, at which time a user can replace the entire set of ink-related components for a particular color. Similarly, the printhead service module is designed for reliable performance for the expected useful life of the printhead cartridge. This system enables the entire ink delivery system to be replaced for different printing needs, such as replacing indoor dye-based inks with outdoor pigment based inks. | 1 |
FIELD OF THE INVENTION
The present invention relates to compositions of matter having utility in maintaining oral health. It also relates to methods of making such compositions, and the incorporation of same into pharmaceutically suitable vehicles for use in oral health care. More particularly, the invention relates to alkyl derivatives of arginine, optionally in combination with fluoride compounds, and their utility in maintaining oral health.
BACKGROUND OF THE INVENTION
It has been shown that tooth decay and dental disease can be attributed to bacteria forming plaque about the teeth. Growth and proliferation of bacteria is enhanced by the presence of entrapped food particles between the teeth. The removal of plaque and entrapped food particles reduces caries, reduces the tendency towards gingivitis, and reduces mouth odor as well as generally improving oral hygiene.
The prior art recognizes mechanical oral hygiene devices serving to clean the mouth of debris and remove plaque from teeth, such as toothbrushes, flosses, and toothpicks. It also recognizes compositions mostly used in conjunction with such devices but which impart a chemical action in cleaning teeth, such as dentifrices and rinses. In addition to these, various dental coatings and sealants have been applied to teeth as barriers against bacterial action and plaque formation. Another important approach in oral care includes the use of various fluoride-containing preparations which are able to deposit fluoride ions directly onto the surface of tooth enamel. While great advances were made in oral health care by the use of these various approaches, none seem to be completely effective.
A more recent approach to improved oral hygiene involves the recognition that bacteria present in the oral cavity metabolize dietary sugars, such as glucose and sucrose, to organic acids, such as acetic, propionic and lactic acids. The production of these acids results in a rapid drop in plaque pH. If the pH drops to a level of about 5.5 or below and remains there for more than a short period of time, the tooth enamel will begin to demineralize. This process, if repeated over a substantial period of time, will eventually lead to the development of caries. To correct for the pH drop, the saliva contains a pH-rise factor which moderates the extent and duration of the pH drop when glucose and sucrose are metabolized by oral bacteria. This factor was identified as an arginine-containing tetrapeptide. See, for example, Kleinberg, I., Kanapka, J. A., and Craw, D. "Effect of Saliva and Salivary Factors on the Metabolism of the Mixed Oral Flora" Microbial Aspects of Dental Caries, Vol. II, pp. 433-464 (1976). This pH-rise factor is believed to enter the bacterial cell and either neutralize the organic acids as they form or alter bacterial metabolism so that the acids are not produced.
DISCUSSION OF THE PRIOR ART
U.S. Pat. No. 2,689,170 to King, entitled "Oral Preparation For Inhibition Of Dental Caries", discloses oral preparations for inhibition of dental caries having as the active ingredient a saturated higher series of alkyl acyl amide of a saturated aliphatic monoaminocarboxylic acid compound.
U.S. Pat. No. 4,154,813 to Kleinberg, entitled "Means And Method For Improving Natural Defenses Against Caries", discloses a method for supplementing the body's resistance to caries by providing a pH-rise factor which is a peptide of 2-4 amino acid units, one or more of which is arginine.
U.S. Pat. No. 4,225,579 to Kleinberg, entitled "Means And Method For Improving Defenses Against Caries", claims peptides of 2-4 amino acid units, one or more of which is arginine, for combatting caries. These arginine-containing peptides are disclosed to penetrate dental plaque and bacteria in the mouth and to counteract acid produced as a result of metabolism of carbohydrates.
British Pat. No. 1,352,420 to Yoshinaga et al, entitled "Novel Arginine Derivatives, Their Production And Their Use", discloses N.sup.α -acylarginines having antibacterial or germicidal properties for use in oral hygiene.
U.S. Pat. No. 3,809,759 to Bocher and Faure, entitled "Pharmaceutical Composition For Treating Mental Fatigue Containing Arginine-Potassium Phospho-Citro-Glutamate And Method Of Using The Same", discloses arginine-potassium phospho-citro-glutamate in pharmaceutical compositions, such as, granules, pills, tablets, and capsules for systemic treatment of mental fatigue.
U.S. Pat. No. 4,061,542 to Demny and Maehr, entitled "2-Methyl-L-Arginine Produced By Cultivating Streptomyces Strain", discloses the title compound for use as an antibiotic and antibacterial agent. U.S. Pat. No. 4,125,619 to Okamoto et al, entitled "N.sup.α -Naphthalenesulfonyl-L-Arginine Derivatives And The Pharmaceutically Acceptable Acid Addition Salts Thereof", discloses the title compounds for use as pharmaceutical agents for the inhibition and suppression of thrombosis.
The compounds of the present invention differ from the aforementioned prior art in that we use new and novel derivatives of arginine in which the polar character of the arginine molecule is modified by the presence of lipid-like substituents. This modification is believed to permit such arginine derivatives to more readily penetrate the phospholipid-containing cell wall of oral bacteria and to inhibit acid production of these bacteria.
Accordingly, one object of the present invention is to provide new and novel derivatives of arginine.
Another object of the present invention is to provide compositions containing an arginine derivative for use in oral applications.
Still another object of the present invention is to provide compositions containing an arginine derivative in combination with a fluoride compound for use in oral applications.
It is still a further object of the present invention to provide methods of preparing such compounds and compositions.
SUMMARY OF THE INVENTION
Oral compositions of the present invention comprise N G -alkyl derivatives of arginine of the formula: ##STR1## where y is an integer from 0 to about 29, preferably from about 5 to about 19, and most preferably from 9 to 15.
The N G -alkyl derivatives of arginine where y is not more than about 19 are preferred since these derivatives possess greater activity against oral bacteria than the higher members of the series.
In general, N G -alkyl derivatives of arginine may be prepared by first preparing the sodium salt of N.sup.α -CbZ-L-arginine. This salt is then allowed to react in a mole ratio of 2:1 with an alkyl halide, preferably a bromide. The crude N.sup.α -CbZ-N G -alkyl derivative is isolated by pouring the reaction mixture into ice water and acidifying with glacial acetic acid. The crude derivative is dried and the N.sup.α -CbZ group removed by catalytic hydrogenolysis. The crude N G -alkylarginine thereby obtained is purified by column chromatography.
The present invention also encompasses pharmaceutically acceptable salts of the N G -alkyl derivatives of arginine such as those formed by reaction of an organic or inorganic base with the acidic (--COOH) portion of the alkylarginine molecule, and those formed by reaction of an organic or inorganic acid with the basic amino or guanidino portions of the alkylarginine molecule. Typical salts are those of the formula ##STR2## wherein y is an integer of from 0 to about 29; M is H, Na, K, Mg, Ca, Ag, Ce, Mn, Zn or the residue of a strong organic base; m and n are 0 or 1; and HX is HCl, HNO 3 , H 2 SO 4 , CH 3 COOH or gluconic acid ##STR3##
The present invention provides oral compositions of an N G -alkyl derivative of arginine in the form of a mouthwash, spray, dentifrice, gel, powder, solution, lotion, varnish, lozenge, chewing gum, slow releasing device and the like for use in oral hygiene in combatting bacteria and to increase pH of the oral fluids.
The present invention further provides oral compositions of N G -alkyl derivatives of arginine with a fluoride compound, such as, sodium fluoride, zinc fluoride, stannous fluoride, sodium monofluorophosphate, acidulated phosphate fluoride, ammonium fluoride, ammonium bifluoride and amine fluoride.
DETAILED DESCRIPTION OF THE INVENTION
N G -alkyl derivatives of arginine are prepared according to the following general procedure.
The sodium salt of N.sup.α -CbZ-L-arginine is prepared by reacting N.sup.α -CbZ-L-arginine with sodium ethoxide in ethanol and evaporating to dryness. The dry salt is dissolved in N,N-dimethylformamide and the solution cooled to 5° C. An alkyl halide in DMF is added dropwise to the cold solution to provide a mole ratio of alkyl halide to N.sup.α -CbZ-L-arginine sodium salt of 1:2. The reaction mixture is brought to room temperature and stirred for 24 hours. The mixture is then chilled and diluted by pouring into ice water, and a solid product precipitated by adjusting the pH to 6 using glacial acetic acid as necessary. The precipitated solid is washed with water and allowed to air dry, then dissolved in a mixture of ethanol and glacial acetic acid. After adding a palladium-on-carbon catalyst, the mixture is shaken in an atmosphere of hydrogen gas to remove the N.sup.α -CbZ group by catalytic hydrogenolysis. The solution is then filtered and the filtrate evaporated to dryness. The residual solid is dissolved in a small amount of a 1:1 butanol-acetic acid mixture and the solution added to a column packed with silica gel. The column is eluted with 7:2:2 butanol-acetic acid-water. The fraction containing the product are combined and the solution is evaporated to dryness. The solid product obtained is the desired N G -alkylarginine.
A more complete understanding of the process for preparing compounds of this invention and oral compositions comprising such compounds will be obtained by reference to the following specific examples, which are included for purposes of illustration only and are not intended to be limiting.
EXAMPLE 1
Preparation of N G -decylarginine
A solution of sodium ethoxide was prepared by reacting 4.6 g (0.20 mole) of sodium metal with 473 ml of abs. ethanol. To this solution, 61.67 g (0.20 mole) of N.sup.α -CbZ-L-arginine was added with stirring over a 2 minute period and while maintaining a nitrogen blanket over the ethoxide solution. The mixture was warmed on a steam bath with vigorous stirring until all the solid had dissolved. The solution was then evaporated to dryness, first using a rotary evaporator at 35° C. followed by more complete drying under vacuum at room temperature to obtain the sodium salt of N.sup.α -CbZ-L-arginine as a white solid. This material was dissolved in 250 ml of dry N,N-dimethylformamide and placed in a 1 liter flask equipped with a mechanical stirrer, drying tube, nitrogen inlet, addition funnel and thermometer; 22.12 g (0.10 mole) of 1-bromodecane were added to the flask dropwise during 1.5 hours while the reaction mixture was stirred vigorously and kept under a nitrogen blanket. After the addition was complete, stirring was continued at room temperature and under nitrogen for a period of 9 days. The bright yellow reaction mixture was filtered to remove insoluble material and poured over 1500 g of a mixture of ice and water. A taffy-like solid precipitated and the mixture was poured into a separatory funnel and extracted with diethyl ether. The resulting solid was dried in a rotary evaporator at 40° C., followed by more complete drying under vacuum at room temperature. The resulting product was N.sup.α -CbZ-N G -decylarginine having the formula: ##STR4## Five grams (11.1 mmole) of crude N.sup.α -CbZ-N G -decylarginine were dissolved in 25 ml glacial acetic acid. To this solution was added 100 ml of abs. ethanol and a suspension of 0.30 g 10% palladium on activated carbon catalyst in 10 ml glacial acetic acid. This mixture was treated with hydrogen on a Parr hydrogenator. The hydrogenator bottle was pressurized to 2 atmospheres with hydrogen. The mixture was shaken until the pressure dropped to 0.5 atmospheres whereupon the bottle was repressurized to 2 atmospheres and shaking continued. This procedure was repeated until no further loss in hydrogen pressure was experienced. The reaction mixture was thereupon filtered through Celite to remove the catalyst and the filtrate evaporated to dryness, first on a rotary evaporator at 40° C., and finally under vacuum at room temperature. The dry residue was dissolved in a solution of 75 ml n-butanol and 25 ml glacial acetic acid. The solution was concentrated to a volume of 25 ml and the concentrate added to a column of silica gel. The column was eluted with n-butanol-acetic acid-water (4:1:1) and the desired product obtained by combining fractions and evaporating to dryness. The structure of the product was confirmed by nuclear magnetic resonance to be the acetic acid salt of N G -decylarginine having the formula: ##STR5## Exactly the same procedure was used to prepare the following N G -alkyl derivatives of arginine:
N G -laurylarginine (C 12 )
N G -myristylarginine (C 14 )
N G -palmitylarginine (C 16 )
N G -stearylarginine (C 18 )
Representative compounds of the present invention were assayed to determine their effectiveness in reducing acid production from sugar by S. Mutans as a measure of their efficacy in oral compositions.
ASSAY FOR INHIBITORS OF GLYCOLYSIS
This assay measures the rate of acid production from the metabolism of sucrose by Streptococcus mutans 6715. The assay solution consists of 10.00 ml of a phosphate buffer at pH 5.5 under nitrogen. To this solution are added 8×10 9 cells of S. mutans 6715, followed by 50 μl of 25×10 -3 M sucrose. A known volume of a 10 mg/ml solution of the test arginine derivative in then added, and the rate of acid production is monitored with the automatic addition of a 5×10 -3 N KOH solution by a pH-stat.
Table I illustrates acid inhibition activity of the indicated compounds in terms of the concentration of compound required to effect a 50% reduction in the rate of acid formation.
TABLE 1______________________________________ Concen- trationArginine Derivative (W/V %)______________________________________N.sup.G --Decylarginine 6.0N.sup.G --Laurylarginine 1.0N.sup.G --Myristylarginine 0.5N.sup.G --Palmitylarginine 3.0N.sup.G --Stearylarginine 1.0______________________________________
Oral compositions of the present invention include the combination of N G -alkyl derivatives of arginine with a fluoride compound, e.g. sodium fluoride, zinc fluoride, stannous fluoride, sodium monofluorophosphate, acidulated phosphate fluoride, ammonium fluoride, ammonium bifluoride and amine fluoride. In general, the N G -alkyl derivative of arginine should be present in an effective amount up to a saturated solution, while the fluoride ion should be present from as low as 0.0001% to 10%.
The preferred concentration of the N G -alkyl derivative of arginine is 0.05 to 10%, while that of the fluoride ion is 0.001 to 1.0%. The most preferred concentration of N G -alkyl derivative of arginine is 0.5 to 5%, and the fluoride ion, 0.01 to 0.1%. While higher concentrations of both N G -alkyl derivatives of arginine and fluoride ions could be used, no particular advantage is afforded thereby.
While it is presently preferred to have a polyol-containing aqueous vehicle as an acceptable carrier for the above composition, other nonaqueous compositions are not excluded from the list of suitable carriers, as for example various alcohols, polyols, and dimethylsulfoxide.
The composition of this invention may be in the form of a mouthwash, spray, dentrifrice, gel, powder, solution, lotion, varnish, lozenge, chewing gum, slow releasing device or other forms suitable for oral application. Any pharmaceutically acceptable materials such as those ordinarily used in such oral compositions that are compatible with N G -alkyl derivatives of arginine and fluoride ions may be employed in the compositions of this invention.
In accordance with the present invention, the compositions are supplied to teeth with an appliance, e.g., toothbrush, swab, impregnated dental floss and the like by gently brushing the teeth, both the buccal and lingual sides, at least once daily. The most preferred application of the above compositions to teeth is from lozenge and from chewing gum, whereby one slowly dissolves the lozenge in the mouth over 10 to 15 minutes, and by chewing the gum over 30 to 45 minutes after each meal.
The following examples will further serve to illustrate typical oral compositions of this invention.
EXAMPLE 2
(Mouthrinse)
______________________________________ w/w %______________________________________Glycerol, U.S.P. 10 to 40N.sup.G --alkylarginine 0.1 to 5NaF 0.2Flavors 1.0Preservatives 0.3Pluronic F-108 2.0Water, q.s. to 100 parts______________________________________
The N G -alkyl derivative of arginine was dissolved in water with continuous stirring at 80° C. The remaining ingredients were dissolved in glycerol and mixed with the N G -alkylarginine solution at room temperature.
EXAMPLE 3
(Gel Dentifrice)
______________________________________ w/w %______________________________________Pluronic F-127 20.0Flavors 0.8Preservatives 0.3N.sup.G --alkylarginine 2.0Water, q.s. to 100 parts______________________________________
EXAMPLE 4
(Gel Dentifrice)
______________________________________ w/w %______________________________________N.sup.G --alkylarginine 2.0NaF 0.2Pluronic F-127 20.0Flavors 0.8Preservatives 0.3Water, q.s. to 100 parts______________________________________
The gels of Examples 3 and 4 were prepared as follows:
The N G -alkylarginine was dissolved in 50 ml water while continuously stirring at 80° C. After the arginine derivative had dissolved, the solution was cooled to room temperature and the NaF (if present) and preservatives were added. Separately, the Pluronic F-127 and flavors were dissolved at 4° C. The solution was allowed to warm up to room temperature and then blended into the arginine containing solution with continuous stirring. The mixture was homogenized and the pH of the gel adjusted to 5.5 by the addition of NaOH or HCl as required.
EXAMPLE 5
(Paste Dentifrice)
______________________________________ w/w %______________________________________N.sup.G --alkylarginine 1 to 5NaF 0.2Glycerol 15.0Sorbitol 10.0Sodium lauryl sulfate 1.2Calcium pyrophosphate 40.0Propylene glycol 10.0Flavors 1.0Preservatives 0.3Pluronic F-127 10.0Water, q.s. to 100 parts______________________________________
The N G -alkylarginine was dissolved in glycerol, sorbitol, propylene glycol, Pluronic F-127 and water at 80° C. The pH was adjusted to 5.5 and the flavors, NaF, preservatives and sodium lauryl sulfate were added. The calcium pyrophosphate was blended into the mixture with continuous stirring at room temperature, and the mixture was homogenized with a roller mill. In this formulation, the sodium fluoride component is optional and may be omitted in the preparation of a non-fluoride dentifrice.
EXAMPLE 6
(Powder Dentifrice)
______________________________________ w/w %______________________________________N.sup.G --alkylarginine 1 to 5Flavors 4.0Sodium lauryl sulfate 2.0Saccharin 0.4Abrasive, q.s. to 100 parts______________________________________
EXAMPLE 7
(Lozenge)
______________________________________ w/w %______________________________________N.sup.G --alkylarginine 1 to 5Sorbitol 20.0Mannitol 20.0Starch 12.0Flavors 2.0Preservatives 0.4Saccharin 0.2Magnesium stearate 0.8Talc 0.5Corn syrup, q.s. to 100 parts______________________________________
The mixture of Example 7 was granulated into a homogeneous blend and pressed into a lozenge.
Although the present invention has been described with reference to particular embodiments and examples, it will be apparent to those skilled in the art that variations and modifications of this invention can be made and that equivalents can be substituted therefore without departing from the principles and the true spirit of the invention. | Oral hygiene formulations incorporating N G -alkyl derivatives of arginine, or the pharmaceutically acceptable salts thereof, optionally in combination with fluoride compounds, are effective in combatting microorganisms, inhibiting acid production and reducing dental caries. | 0 |
RELATED APPLICATIONS
[0001] This application is the national stage, under 35 USC 371, of PCT/EP2015/081065, which was filed on Dec. 22, 2015, which claims the benefit of the Jan. 12, 2015 priority date of German application DE 10-2015-100346.5, the contents of which are herein incorporated by reference.
FIELD OF INVENTION
[0002] The invention relates to a cluster packs, and in particular, to cluster packs in which containers of the cluster pack are glued to each other.
BACKGROUND
[0003] A container typically has a circular cross-section. However, the diameter of the section is not constant as a function of height along the container. Many containers have a container wall that, at some height, has a diameter that is greater than the container's diameter at other heights. This section is often called a “ring” or “rolling ring.”
[0004] When containers of this type are glued to form a cluster pack, there is a risk that the containers will tear when being separated. In particular if they are connected by glued joints in the lower half of the containers, the resulting leverage that arises during container separation is substantial.
SUMMARY
[0005] In one aspect, the invention features a cluster pack having at least two containers that are interconnected by a glued joint. The containers have a wall that comprises a wall reinforcement in the region of the glued joint or adjacent to the glued joint. The wall reinforcement resists forces that arise when one attempts to detach a container from the cluster pack. This helps avoid tearing the container itself.
[0006] The wall reinforcement is preferably only provided locally. This avoids using excessive amounts of material just to make the wall reinforcement. However, in an alternative embodiment, the wall reinforcement extends circumferentially around the container wall.
[0007] Bottles usually comprise a region with a greater outer wall diameter than the cylindrical basic body of a walled bottle. This region, which is called a “rolling ring,” has a greater outer wall diameter than that of the rest of the bottle but otherwise has the same wall thickness. This is the region that contacts other containers or that engages conveyors or guiding tools. In a preferred embodiment, the glued point or glued joint is arranged at the rolling ring.
[0008] As used herein, “container” refers to bottles, cans, tubes, and sachets, in each case made of metal, glass, plastic, and/or a material composite, typically, for example, PET bottles or a material composite of plastic, aluminum foil, and paper. All materials can comprise the containers, in particular such as are suitable for filling with fluid or viscous products. The term “containers” also include containers that are already assembled into groups, i.e., multi-packs. The containers of the cluster pack are preferably arranged in non-nesting positions, i.e. the containers of one row of the cluster pack are not arranged in the gaps of an adjacent row of the cluster pack.
[0009] The containers can have any cross-section, including oval, circular, and polygonal. A container can be shaped like a sachet, pyramid, or parallelepiped. However, a container is frequently cylindrical, either fully or in sections. Examples of fully cylindrical containers include cans. Examples of containers that are cylindrical in sections include bottles, which start from a cylindrical basic body and tapers towards the opening, and/or with the bottle standing at the lower end on point-like support regions, and with the bottle wall transforming in transition sections from the point-like support regions towards the basic body and into the cylindrical bottle wall. A container has a height that is measured from the lower end, upon which the container stands on a support surface, to an upper end, which, in most cases, includes the container's opening.
[0010] To significantly reduce the likelihood of tearing, it is sufficient for the container wall to be configured in the region of the wall reinforcement so that it is at least 5% thicker than the rest of the wall. In some cases, it is at least 10% thicker. In others, it is at least 30% thicker. And in still others, it is thicker by at least 50%. The dimension of the wall reinforcement to be selected in each case is to be selected by the person skilled in the art as a function of the size and shape of the container and of the wall thickness. The thicker the container wall is to begin with, the less wall reinforcement would be required.
[0011] In some embodiments, the wall reinforcement is applied in sections.
[0012] In certain embodiments, the diameter of the wall reinforcement is at least 3% greater than that of the glued joint that is to be applied. Preferably, the diameter of the wall reinforcement is at least 15% greater than that of the glued joint that is to be applied.
[0013] In other embodiments, the diameter of the wall reinforcement is selected such that its surface area is at least 3% greater than that of the glued joint that is to be applied. Preferably, the diameter of the wall reinforcement is selected such that its surface area is at least 15% greater than that of the glued joint that is to be applied.
[0014] The size of the wall reinforcement that is to be applied in sections to the container wall is selected to minimize the use of additional material. This makes manufacturing the containers more economical. The slightly greater diameter of the wall reinforcement makes it easier to apply the glue without missing the wall reinforcement. This makes container manufacture easier since greater tolerance can be permitted.
[0015] The wall reinforcement's greater diameter also improves the force conditions when the container is detached from the cluster group. According to an advantageous embodiment of the invention, if appropriate, a greater diameter of the wall reinforcement can be integrated with a reduced thickening of the container wall. The same applies to a further preferred embodiment of the container wall, with which the wall reinforcement comprises surface area at least 3% larger than the glued joint to be applied on the wall reinforcement.
[0016] The shape of the wall reinforcement is purposefully determined in accordance with the shape of the glued joint that is to be applied. The wall reinforcement can be circular, oval, or polygonal. In a preferred embodiment, it forms a plateau having a circular or oval base. In other embodiments, it surrounds the glued joint as circumferential ring-shaped wall reinforcement. In yet other embodiments, it partially overlaps the glued joint.
[0017] In some embodiments, the wall reinforcement is a ring that spans the entire circumference and that extends inwards towards the container's axis. This ring has is flush with the container's outer surface such that the outer surface remains undisturbed or uninfluenced by the reinforcement. The reinforcement can be cylindrical or cambered. Or it can have a design pattern, such as grooves, structures, or other shapes that can span the container's surface. These features could then extend undisturbed into the reinforced wall region.
[0018] In particular with glued joints that occupy a substantial surface area, it may prove advantageous for the wall reinforcement to be applied, for example, only in the outer region of the glued joint. As a result, the wall reinforcement surrounds the glued joint but does not span it. Such an arrangement strengthens the resistance of the container wall against the forces incurred at the detachment of the container from the cluster pack, while at the same time minimizing the use of material.
[0019] In particular applications, the wall reinforcement can also be formed next to the glued joint, immediately adjacent to it, or partially overlapping, for example in situations in which, at the detachment of the container from a cluster pack, tension peaks occur in the area surrounding the glued joint, which frequently lead to the tearing of the container.
[0020] According to a particularly preferred embodiment of the invention, the transition from the wall reinforcement to the container wall is configured as a tapering transition region. Such a transition region with tapering wall thickness avoids the occurrence of tension peaks at the detachment of a container from the cluster pack, and therefore ensures, even with a reduced wall reinforcement, that the tearing of the container will be avoided
[0021] The method according to the invention for producing a cluster pack with at least two containers, at least one if which has a reinforced wall section, includes providing a container preform in which there is a thicker application of material at a predetermined location, producing a first container from the preform, wherein the first container comprises a wall reinforcement at the location of the thicker application of material, aligning the first container in relation to a glue applicator in such a way that the glue is applied such as to produce a glue point on the wall reinforcement or adjacent to it, and attaching a second container by pressing it against the glue point of the first container.
[0022] The method according to the invention makes provision that, already at the provision of preforms for containers, these preforms comprise a thickened application of material at predetermined points. The thickened application of material by the layering of material sections, wherein the material sections additionally layered onto the preform are preferably of the same material as the preform or the container wall derived from it, typically, for example, polyethylene terephthalate (PET). The layered material section is preferably thinner than the material thickness of the preform, but, if necessary, can also be thicker. According to an advantageous embodiment of the method according to the invention, the additional material section is fixed on the preform at a predetermined point, for example integrally with the production of the preform, such as by casting or injection molding, by applying more material at the predetermined point. As an alternative, the material section can also be adhesively bonded or welded to the material of the preform. A container is then produced from the preform in an inherently known manner. This container then comprises a container wall that is provided in sections with a wall reinforcement, and specifically at the point at which the preform had a location of thickened material application.
[0023] According to the invention, the container that comprises a container wall with wall reinforcement is now aligned in such a way that the means for the application of glue, typically a nozzle, applies the glue onto or adjacent to the wall reinforcement. The alignment of the containers is carried out by inherently known means for rotating containers. Sensors that can detect a different material thickness in the container wall are likewise known.
[0024] The first container, which has a glue point on or in the vicinity of a wall reinforcement, is then joined to a second container, usually in that the containers are pressed against one another, for example by clamp strips, and, if necessary, the glue that is now present on both containers is hardened or cross-linked.
[0025] According to an advantageous embodiment of the invention, the second container, on which no glue point has been applied, nevertheless also comprises a wall reinforcement, since the forces that lead to the tearing of the container take effect not only on the container on which the glue point was applied, which, as a glued joint, now connects the first and second containers. With this embodiment of the invention, the second container is also aligned, before the joining, in such a way that its wall reinforcement, or regions of the container wall adjacent to the wall reinforcement, is or are pressed onto the glue point on the first container.
[0026] The production of a glued joint between two containers from a glue point applied onto one container takes place by the compacting or pressing the two containers against one another, wherein the glue of the glue point connects the two containers at a glued joint.
[0027] As used herein, “glue” refers to any substance that is suitable for the production of a glued connection between two containers, in particular such substances, materials, or compounds which, when applied in the fluid or viscous state, form a self-bonding glue point, but also such substances, materials, or compounds which, by the application of energy, for example by the application of pressure, radiation, or temperature, or by means of chemical hardening or cross-linking, build up a glued joint. Typical glues are UV-hardening glues, that can also be processed in a low-viscosity state and can be hardened by radiation, or a hot glue, that cools after application and that, below a temperature typical for the material, varies in its adhesive strength, such that hot glue is only suitable for the immediate formation of a glued joint. As used herein, glues can include multi-layered materials, e.g. such as one of at least one carrier material, which is coated with a glue in such a way that a glued joint can be produced between two containers. Typically, these multi-layered materials are formed as pads, which are formed as adhering or adhesive on two sides.
[0028] A container formed with a glue point therefore comprises glue that is applied at a point, along a line form, or in some pattern of points or lines. Preferably, the glue is selected such that its adhesive strength is low enough to permit detachment of a container from the cluster pack by hand. UV-hardening glues are particularly suitable because the adhesive strength that the glue develops at the glued joint can be adjusted by the composition of the glue and the extent of the hardening.
[0029] The cluster packs according to the invention are connected to one another by glued joints. Preferably, the glued joints connect the cluster packs directly to one another. For further preference, the glued joints represent the exclusive or sole connection of the containers of a cluster pack. According to an advantageous embodiment, however, it is also possible for a cluster pack to be provided at its upper end with a transport securing element, in particular a transport securing element in the form of a band. According to a further preferred embodiment of the invention, the transport securing element can be lengthened to a carrying loop. Preferably, the glue points and the glued joints derived from them are configured to be as small as possible, in order to economize on glue.
[0030] The application of the glue takes place by way of nozzles that apply or spray the mostly liquid glue directly onto a container to form one or more glue points. After the application of the adhesive, the containers are joined, for example by the effect of clamp strips, which bring a plurality of containers into contact, such that, at the locations at which a glue point has been applied on a first container, a glued joint is formed by bringing a second container without a glue point into contact with the first. The second container can likewise comprise a glue point at the location at which the first container comes in contact, such that a glued joint can be formed from two glue points.
[0031] A device according to the invention for producing a cluster pack with at least one first and one second container, in each case comprising a container wall, is characterized in that the device comprises means for conveying a first and a second container, means for aligning a first container, means for applying a glue point on the first container, and means for joining the first and the second container to form a cluster pack, wherein the means for aligning the first container align the first container with the provision that the means for applying a glue point take effect on or adjacent to a wall reinforcement, which is comprised in the container wall of the first container.
[0032] In another aspect, the invention features a device that comprises means for alignment, which align the second container before the joining, with the provision that, at the joining of the first and second containers, a wall reinforcement of the second container is joined to or adjacent to the glue point of the first container.
BRIEF DESCRIPTION OF THE DRAWINGS
[0033] These and other features and advantages of the invention will be apparent from the following detailed description and the accompanying figures, in which:
[0034] FIG. 1 shows a longitudinal section of a container with a wall reinforcement in the form of a point, and
[0035] FIG. 2 shows a longitudinal section of a container with a circular wall reinforcement at a roll ring.
[0036] The above figures are not drawn to scale. Certain features have been exaggerated to promote clarity of expression.
DETAILED DESCRIPTION
[0037] FIG. 1 shows first and second PET (polyethylene tetraphthalate) bottles 2 a, 2 b. Each bottle 2 a, 2 b has a wall 4 having a thickened wall section 6 . Outside of the thickened wall section 6 , the wall thickness is typically about 0.15 millimeters.
[0038] The thickened wall section 6 is where a glue point is to be applied in order to form a glued joint. An application of wall reinforcement 8 in the thickened wall section 6 increases the wall thickness. In some embodiments, the thickness increases by about 30%. In other embodiments, the thickness increases by an amount somewhere between 0.15 millimeters and 0.2 millimeters. In either case, the thickened wall section 6 suppresses the risk of damage when attempting to detach a first bottle 2 a from a second bottle 2 b to which it has been attached via a glue point as part of the formation of a cluster pack. Preferably, the wall reinforcement 8 is applied at a point about halfway up the bottles 2 a, 2 b.
[0039] In the illustrated embodiment, the wall reinforcement 8 is as a circular surface area, the diameter of which is 10% greater than that of the glue point that is to be applied. The surface of the wall reinforcement 8 is more than 3% larger than the surface of the glued joint. In the illustrated embodiment, the wall reinforcement 8 is a circular lens with a flattened edge region. This configuration reduces material usage.
[0040] This wall reinforcement 8 avoids tension peaks that normally arise when detaching the first and second bottles 2 a, 2 b from each other. This reduces the risk of tearing a bottle 2 a, 2 b.
[0041] In order to be able to add further bottles to the first and second bottles 2 a, 2 b to form a larger cluster pack, it is useful to apply two additional wall reinforcements 8 onto mutually opposed sides of the first and second bottles 2 a, 2 b. The bottles 2 a, 2 b are aligned before the application of the glue point in such a way that the glue point is applied onto the wall reinforcement 8 .
[0042] In some cases, it is useful for the glued joint to make contact at a wall reinforcement on each of the two bottles connected to one another. To achieve this, the bottles 2 a, 2 b to be connected are aligned before joining them in such a way that wall reinforcements 8 applied in the form of points come into contact.
[0043] FIG. 2 shows another PET bottle 2 having a wall 4 that has a roll ring 10 formed at the lower end thereof. The roll ring 10 extends circumferentially around the cylindrical bottle 2 and thus defines a portion of the wall 4 that has an external diameter that is greater than that of other portions of the wall 4 . However, the wall 4 does not have a greater wall thickness in the region of the roll ring 10 . Instead, the wall 4 has a constant 0.15 millimeter thickness.
[0044] In the embodiment of FIG. 2 , the glue point is applied at the roll ring 10 to produce a glued joint. When the bottles are detached, the leverage gives rise to high forces that act on the lower end of the bottle 2 . As a result, it is useful to provide the roll ring 10 with a wall reinforcement 8 , which is typically also made of PET. This wall reinforcement has a wall thickness that is about 40% greater than that of the wall 4 .
[0045] In the embodiment shown in FIG. 2 , the wall reinforcement 8 extends circumferentially all the way around the bottle. This consumes more material than was the case when the wall reinforcement amounted to a point. However, it also provides the advantage of dispensing with the need for careful alignment. This simplifies bottle manipulation.
[0046] A practical method for making a bottle 2 as described above is to start with a preform that is made from whatever plastic the bottle is to be made of. In those cases where the preform is produced by casting, the mold can have cut-outs or indentations that form wall sections having different thicknesses. By suitably shaping the mold, these sections of reinforced wall thickness, or wall reinforcements 8 , can be configured as points, flat areas, or rings that extend circumferentially around the bottle.
[0047] The dimensions of the wall reinforcement 8 depend on those of the glue points. Typically, the wall reinforcement 8 has diameter that is greater than that of the glue points. Preferably, the diameter is 10% greater.
[0048] In some embodiments, the cut-outs are shaped to form a tapering edge region at the wall reinforcement 8 . The thickness of the tapering edge region at the wall reinforcement 8 is the same as the maximum thickness of the wall reinforcement 8 . As one traverses the tapering edge region away from the wall reinforcement 8 , this thickness decreases until it matches that of the surrounding wall 4 .
[0049] An alternative bottle-manufacturing method includes introducing additional material into the mold's indentations or cut-outs onto which the material of the wall 4 is then applied. The additional material and the material of the wall 4 adhesively bond or fuse with one another. As a result, the wall 4 comprises at least one wall reinforcement 8 . Although this alternative method is more elaborate than the other methods described herein, it is useful in certain cases, for example if the material of the wall reinforcement 8 is not identical to that of the wall 4 .
[0050] In either case, once the preforms have been made, they are then molded to form bottles that comprise one or more wall reinforcements 8 at predetermined points.
[0051] Forming a cluster pack from the bottles 2 next includes rotating the bottles into alignment relative to a glue applicator. The glue applicator then applies the glue through a nozzle to form a glue point on the wall reinforcement 8 . The bottles are then brought into a position that permits clamping strips press them together in such a way that the walls of the bottles contact each other at the glue point. The glue is then treated to promote hardening or cross-linking, depending on the type of glue being used. Treatments include exposure to radiation, heating, drying, and/or cooling.
[0052] Once the glue hardens or undergoes cross-linking, the glued joint forms and the cluster pack is stable. Thanks to the wall reinforcements, it is possible to remove or detach a bottle from the cluster pack without risk of damaging any bottles.
[0053] Embodiments include those in which only the first bottle 2 a has a wall reinforcement 8 as well as those in which both the first and second bottles 2 a, 2 b have wall reinforcements 8 . | A cluster pack comprises at least two containers connected by a glued joint. One of the containers has a thickened wall region in the region of the glued joint. This region acts as a well reinforcement to reduce the risk of tearing a container during detachment from the cluster pack. | 1 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to apparatus employed to inject fluids into the flexible tube of an intravenous (I.V.) delivery set and more particularly relates to a novel injection site apparatus.
2. Description of the Prior Art
Several different types of injection site apparatus are presently commercially available. Prior art injection site apparatus require that the flexible tube of the intravenous set be cut or broken and that the injection site apparatus be inserted in series therewith. Connecting the severed ends or intermediate ends of the flexible tubes to the injection site apparatus presents several problems. When the flexible tube does not properly bond to the injection site housing leakage and/or contamination occurs. Prior art bonded connections have presented the possibility that an incomplete seal or weak seal will be made.
Most prior art injection site housings have spaces therein which entrap air. Further, the entrapped air can be administered to a patient when it passes out of the space in the injection site housing and into the flexible tube of the delivery set. The entrapped air in the prior art injection site apparatus could sometimes be removed with difficulty by inverting the housing, flushing and purging the air space in the injection site apparatus.
Some prior art injection site apparatus have no effective needle guides which permits the hypodermic needle to pierce the side of the housing or the flexible tube of the I.V. set or the connections between the housing and the flexible tube. It has been observed that such apparatus will permit the hypodermic needle to gouge into the housing so as to remove particles of the plastic housing which are flushed into the patient. The tip of the hypodermic needle can also become bent and unusable again. The hypodermic needle can become lodged into the side wall of the flexible tube so as to prevent flow of fluid. The hypodermic needle may be started into the side wall of a piercable closure in a manner which causes enough resistance to bend the hypodermic needle before it can enter into the fluid chamber of the injection site apparatus.
It would be desirable to eliminate the common problems of the prior art injection site apparatus in a simpler and cheaper structure.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a novel injection site apparatus.
It is another object of the present invention to provide an injection site apparatus which eliminates the possibility of air entrapped in the injection site housing from entering into the flexible tube of the I.V. delivery set.
It is another object of the present invention to provide a novel injection site apparatus which attaches to an unbroken portion of the flexible tube of an I.V. delivery set.
It is another object of the present invention to provide a simple an inexpensive injection site apparatus which enhances the ease of use.
It is another object of the present invention to provide an injection site apparatus which has a minimum number of surfaces to be sealed.
It is another object of the present invention to provide a novel needle guide for an injection site apparatus which eliminates the possibility of a hypodermic needle being inserted improperly into the apparatus.
Accordingly, there is provided an injection site apparatus having a recessed channel in the tube housing for receiving an unbroken section or portion of the flexible tube of an I.V. delivery set. The recessed channel supports and bends the flexible tube in the tube housing. A needle guide and a piercable closure in the housing are axially aligned with a portion of the flexible tube in the tube housing in a manner which directs the hypodermic needle through the side of the flexible tube and into the center or inside hollow area of the flexible tube.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an enlarged side elevation view of a preferred embodiment injection site apparatus;
FIGS. 2 and 3 are end views of the injection site apparatus of FIG. 1;
FIG. 4 is an enlarged elevation view of a modified embodiment injection site apparatus;
FIG. 5 is an end view of the modified embodiment structure of FIG. 4;
FIG. 6 is an end view of yet another modified embodiment injection site apparatus;
FIG. 7 is an enlarged elevation of another modified embodiment injection site apparatus;
FIG. 8 is a modified partial section in elevation of the needle guide portion of the structure of FIG. 1.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Refer now to FIGS. 1 to 3 showing a preferred embodiment of the injection site apparatus 10. The flexible tube 11 of an I.V. delivery set is shown passing through tube housing 12. Tube housing 12 is provided with a recess channel 13 having a circular portion 14 and a converging tapered insert guide 15. The circular portion 14 embraces more than 180 degrees of the circumference of the flexible tube 11.
The flexible tube 11 and its tube housing 12 must provide a sterile environment. Accordingly, the injection site apparatus 10 may be sterilized after being placed on the flexible tube 11 employing prior art sterilizatation means or processes. Further, the flexible tube 11 may be snapped into the tube housing 12 with an antiseptic solvent type cement therebetween which provides self sterilization. Tube housing 12 is preferably made of a non-toxic grade of a semi-rigid plastic such as the polystyrenes, the polycarbonates and/or acrylics.
A piercable hypodermic closure receiver 16 is formed as a recess in the end of tube housing 12. A piercable closure 17 of the well known resilient type is mounted in the piercable closure receiver 16 and held in place therein by secondary needle guide 18 which also forms a sealing ring for compressing the piercable closure 17 in the receiver 16. Preferably, piercable closure 17 and receiver 16 are cylindrical in shape and the sealing ring 18 is formed as an annular ring.
Primary needle guide 19 is formed in the tube housing 12 intermediate the piercable closure receiver 16 and the recess channel 13. Recess channel 13 comprises an outlet portion 21 which is axially aligned with the primary needle guide 19 and the secondary needle guide 18. The inlet portion 22 of recess channel 13 is formed at an angle with outlet portion 21 so as to cause the flexible tube 11 to be bent and to expose a side wall surface to the small diameter end of primary needle guide 19. It will be understood that when a hypodermic needle is inserted through the secondary needle guide 18 it is guided through the center of the piercable closure 17 and into the large diameter end of the primary needle guide 19. Then it is aligned as it passes through the small diameter end of the primary needle guide 19 directly into alignment with the inside diameter of the flexible tube 11 in the outlet portion 21 of recess channel 13.
When the hypodermic needle is inserted through the side wall of flexible tube 11, there is no air introduced into the inside of the flexible tube 11 of the I.V. delivery set. When the hypodermic needle is removed from the flexible tube 11 of the I.V. delivery set, the flexible tube 11 closes at the puncture site so as to prevent leakage of fluid therefrom or air therein. The piercable closure 17 prevents any liquid that may seep out of the puncture hole in the flexible tube 11 from escaping from the tube housing 12 and also both seals and holds any air that was already in the primary needle guide 19 from being pulled into or pumped into the flexible tube 11.
Refer now to FIGS. 4 and 5 showing a modified embodiment structure of the preferred embodiment. Recess channel 13 of tube housing 12' is provided with an outlet portion 21 and an inlet portion 22. Also formed in tube housing 12' is a primary needle guide 23 which connects to the outlet portion 21. An extended cylindrical portion 24 of housing 12' forms a piercable hypodermic needle closure receiver for piercable closure 25. Portion 24 is provided with a sealing flange 26 and an aperture or recess 27 in the body or cylindrical portion 24. The secondary needle guide 28 is formed in the extended cylindrical portion 24 of housing 12'. It will be understood that the primary needle guide 23 is longer than the primary needle guide 19 and the secondary needle guide 28 is further removed from the outlet of the primary needle guide 23 so that a hypodermic needle is more accurately axially aligned with the center of the flexible tube 11. Further, the extended cylindrical portion 24 may be manufactured as a separate hat-shaped element and bonded onto a flange on tube housing 12'. The piercable closure 25 is shown as a molded hat-shaped part, but may be made in the form of a flat disk from flat sheet stock instead of making a molded part. The advantage of a flat disk shape piercable closure is that it is cheaper and the amount of resistance to a hypodermic needle may be more easily controlled.
Refer now to FIG. 6 showing an end view of another modified embodiment structure. Tube housing 29 has a recess channel 31 therein comprising a circular portion 32 and a converging tapered guide portion 33. Lock portion 34 of recess channel 31 is adapted to receive tube retainer 35 therein. Tube retainer 35 comprises a circular tube engaging portion 37 and a tube locking portion comprising tapered keys 38. Tube retainer 35 may be provided with a connector portion 39 which may be molded as a separate element.
The diameter of the circular portion of the tube housings 12 and 29 are made slightly smaller than the outside diameter of the flexible tubes 11 so that there is a slight compressive force applied by the tube housings. When tube retainer 35 is snapped into the lock portion 34, it is adapted to apply a slight compressive force similar to that being applied by the tube housings 12. By applying a continuous compressive force to the outside diameter of flexible tube 11, there is provided a pressure seal between the flexible tube 11 and the circular recess portion 32 of tube housing 29.
FIG. 7 shows another modified embodiment in which the preferred embodiment needle guides are integral with closed recess channel 41. Channel 41 is cylindrical in shape and comprises a cylindrical outlet portion 42 and a cylindrical inlet portion 43. The intermediate ends 44 of flexible tube 11 are adhesively bonded into cylindrical recess ends 45 and 46 of tube housing 40. Preferably the cylindrical portions 42 and 43 of the closed recess channel are approximately the same diameter as the inside diameter of the flexible tube 11. It will be understood that a hypodermic needle will be guided by the primary needle guide 19 and secondary needle guide 18 through the center of piercable closure 17 so as to enter the center of axially aligned outlet portion 42 of the recess channel 41 without engaging the side walls. The needle guide 18 is preferably provided with symmetrical tapers. Piercable closure receiver 16 is preferably tapered, thus, needle guide 18 may be machine assembled and ultrasonically welded in place without having to be oriented.
FIG. 8 shows a modified enlarged partial section in elevation of the novel needle guides 18 and 19. Primary needle guide 19' is preferably shaped as a converging cone having its reduced diameter outlet 47 terminating directly in engagement with the side wall of flexible tube 11. When the hypodermic needle 48 passes through the side wall of the flexible tube 11 it causes bulging of the tube against the hypodermic needle 48. In similar manner when the hypodermic needle 48 is inserted through the piercable closure 17', it causes bulging of the resilient piercable closure at the large diameter inlet 49 of the primary needle guide 19' and seals against the sides of needle 48. Secondary needle guide 18' is provided with a reduced diameter outlet 50 which has a larger diameter than the reduced diameter outlet 47 of the primary needle guide 19'. Preferably the large diameter inlet 49 of the primary needle guide 19' is larger than the reduced diameter outlet 50 of secondary needle guide 18'.
Housing 51 is shown having a cylindrical extension 52. A piercable closure receiver 53 is mounted on extension 52 and adapted to hold in compression piercable closure 17'. While the piercable closure 17' is shown with a bulge induced by the hypodermic needle 48, it will be understood that the compressive force of receiver 53 causes piercable closure 17' to extend outward into opening 50, thus, permitting piercable closure 17' to be easily wiped sterile prior to inserting hypodermic needle 48.
The injection sites shown in FIGS. 1, 4 and 8 are adapted to permit the novel needle guides 19, 23 and 19' and piercable closures 17, 25, and 17' to be leak tested prior to use. When an opening is provided in the flexible tube 11 at the needle guide opening 47, leak testing of flexible tube 11 also tests the seal of the piercable closure as well as the outside wall of flexible tube 11 against its housing. The opening in flexible tube 11 may be made prior to being inserted into its housing, at the time of insertion into its housing or by a needle inserted through the piercable closure after assembly of tube 11 into its housing and mounting of the piercable closure thereon.
It will be noted by examination of the enlarged FIG. 8 that the hypodermic needle 48 may be removed from flexible tube 11 and there is no requirement that the puncture in the side wall of flexible tube 11 be completely sealed. No air has been introduced into the inside diameter of flexible tube 11 by virtue of a hypodermic needle 48 being inserted there through, and the small amount of air which is entrapped in primary needle guide 19' cannot be pumped or forced out by the flow of the fluid inside of tube 11. The air in primary needle guide 19' is trapped in a manner which prevents it from entering tube 11 even though fluid from tube 11 may enter primary needle guide 19'. | An injection site apparatus is adapted to be attached to a continuous unbroken portion of a flexible tube of an intravenous delivery set. The apparatus is provided with a recessed channel for supporting and bending a portion of the flexible tube. The apparatus is provided with a piercable closure and a needle guide which are axially aligned with a portion of the recessed channel. The piercable closure and needle guide align a hypodermic needle in axial alignment with the center of said flexible tube to prevent interference therewith. | 0 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention pertains generally to a joint prosthesis and, more particularly, to a system that measures forces on a joint prothesis to determine proper implantation of the prosthesis on a patient.
2. Description of the Prior Art
The human knee is the single largest joint of the human body, but due to its structure, is arguably the most vulnerable to damage. The leg consists principally of a lower bone called a tibia and an upper bone known as the femur. The tibia and femur are hinged together at the knee joint. The knee joint includes femoral condyles supported in an engagement with crescentic fibrocartilages that are positioned on the upper end of the tibia and receive the femur. The joint is held together by numerous ligaments, muscles and tendons. The patella is a similarly supported bone positioned in front of the knee joint and acts as a shield for it.
When the knee joint has been severely damaged from accident, wear, or disease, partial or total knee replacement may be the only viable solution. One type of knee replacement is shown in U.S. Pat. No. 4,340,978 issued to Buechel et al. In this patent, the tibia is resected to form a flat, horizontal platform known as a tibial plateau. The amount of bone structure removed corresponding to the severity of damage to the joint and the necessary allowance needed for the prosthesis. A tibial platform is secured to the tibial plateau with posts or anchors fixed normal or perpendicular to the tibia plateau. The anchors provide additional support to the tibial platform when the joint is subjected to shear, tipping and torque forces present under normal knee articulation.
A femoral component, comprising a curved convex semi-spherical shell, covers the femoral condyles and slidably engages a concave tibial bearing insert. On a side opposite the femoral component, the tibial insert is substantially flat and slidably engages the tibial platform. Interaction of opposing surfaces of these three elements, the femoral component, the tibial insert and the tibial platform allows the prosthesis to function in a manner equivalent to a natural knee joint.
Another tibial platform and a surgical procedure for implantation is described in U.S. Pat. No. 4,822,362 issued to Walker et al.
Crucial to either the complete joint of Buechel et al. or the tibial platform of Walker et al. is proper alignment of the tibial platform on the tibial plateau. Without proper alignment, neither will function correctly whereby uneven forces on the prosthesis may result in excessive contact stresses leading to deformation and/or early wear and thus undesirable short prosthetic life.
Template assemblies have been used in implantation surgical procedures to resect the tibia and align the tibial platform. One such assembly is disclosed in U.S. Pat. No. 4,211,228 issued to Cloutier. This assembly comprises a Y-shaped handle having two flat prongs that are used to check the planes of the resected tibia for overall flatness and to hold temporarily the tibia inserts. An alignment rod, fixed to the flat handle, is aligned visually along the long axis of the tibia, as viewed laterally and anteriorally, to ensure correct positioning of the tibial platform onto the patient's tibia. Since tibial platform alignment does not include movement of the prosthetic components in order to access force loads on the joint, alignment of the tibial platform may not be optimum, realizing pressure differences across the surface of the platform which under normal articulation of the joint may cause fatigue in the prosthesis.
Consequently, there exists a need for a system to dynamically measure and analyze forces present on components of a knee joint prosthesis and all other types of prostheses The system should measure these forces throughout the normal range of motion of the joint, providing quantitative indications of forces present. The system should be easy to install and yet be removable when the analysis is complete.
SUMMARY OF THE INVENTION
The present invention provides a system for dynamically measuring forces applied to a joint prosthesis. The system comprises a first support member attached to an outer surface of a first bone, a second support member attached to an outer surface of a second bone and a transducer secured to at least one support member and engaging the other support member. The transducer measures forces carried between the first and second support members as the prosthetic joint is articulated and provides representative force output signals at selected locations on at least one of the support members.
The present invention further provides a method for aligning a joint prosthesis between two bones of a patient. The method comprises: locating the force transducer between the two bones; articulating the joint to obtain force measurement data, preferably at spaced locations; collecting the force measurement data; and performing curative steps based on the force measurement data to properly align the joint. In the preferred embodiment, a computer is connected to the transducer to receive or collect the force measurement data. The computer includes a display that presents the data to the operating surgeon in any convenient arrangement such as a graphical, numerical or combined format.
In the preferred embodiment, the transducer comprises a central body having an upper surface and a cavity opening to a lower surface. The cavity defines a flexure member in the body that is responsive to forces applied from the joint prosthesis on the upper and lower surfaces. A strain gauge, such as a resistive strain gauge, is secured to the flexure member to measure the response thereof. To localize forces onto the flexure member, the transducer further includes a support post connected to the flexure member. A second end of the post connects to a plate. Since the plate is separated from the upper surface and receives the forces from one of the support members, the forces are concentrated or localized on the flexure member, increasing the sensitivity of the transducer.
The present invention is particularly useful during the implantation of a knee prosthesis where alignment of the joint prosthesis on the patient is critical to its usefulness. This knee prosthesis comprises a femoral component coupled to a femur; a tibial component that includes a cover plate coupled to a resected tibial plateau with spikes or other forms of anchors; and a tibial platform which slidably engages the femoral component to articulate the joint. A transducer is located between the cover plate and the tibial platform. In the preferred embodiment, the transducer body comprises a plurality of integrally formed spaced apart flexure members, each flexure member defined by a corresponding cavity and defining a force responsive flexure section. Each flexure section provides a corresponding representative force output signal proportional to the forces applied to the flexure member. A plurality of support posts coupled to each flexure member and a plate located above the upper surface localize and distribute the forces applied to the plate. The transducer is secured to the cover plate with threaded portions of the spikes, while the tibial platform slidably mounts to the transducer with a dovetail/notch interconnection. Lateral movement of the platform on the transducer is prevented with protruding elements formed on a lower surface of the transducer cooperating with depressions that function as detents on an upper surface of the plate.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a rear perspective view of the present invention comprising a knee prosthesis;
FIG. 2 is a top plan view of a cover plate for the knee prosthesis of FIG. 1;
FIG. 3 is an enlarged front plan view of a spike for the knee prosthesis of FIG. 1;
FIG. 4 is a front plan view of a force transducer mounted on top of the cover plate.
FIG. 5 is a bottom plan view of the force transducer;
FIG. 6 is a top plan view of the force transducer of FIG. 4;
FIG. 7 is a fragmentary sectional view of the force transducer taken along line 7--7 of FIG. 6;
FIG. 8 is a sectional view of the force transducer taken along line 8--8 of FIG. 6 with a tibial platform coupled above;
FIG. 9 is a fragmentary sectional view of the force transducer taken along line 9--9 of FIG. 6 with a tibial platform coupled above;
FIG. 10 is a fragmentary sectional view of the force transducer taken along line 10--0 of FIG. 6;
FIG. 11 is a front view of the knee prosthesis of FIG. 1 coupled schematically to a computer; and
FIG. 12 is a front view of a spacer mounted on top of the cover plate.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The dynamic force measuring prosthesis of the present invention is shown perspectively as assembly 10 in FIG. 1. Assembly 10 comprises a first support member or femoral component 12, a tibial platform 13, a force transducer 14 and a second support member or tibial cover plate 16 which is formed to transfer loads at selected locations between the tibia and the force transducer. When installed as a replacement assembly for a natural human knee joint, assembly 10 provides quantitative feedback on force load balance across the tibial-femoral joint.
Addressing each component separately, femoral component 12 includes a flange 18 formed integrally with two condyles 20. Femoral component 12 includes a pair of fixing posts or anchors 22 integrally formed on an inside surface 24. Posts 22 are used to fix the femoral component 12 to a femur 26, illustrated only in dotted lines.
An outside (lower) surface 28 of flange 18 provides most of the bearing surface for a patella, not shown, which cooperates with femur 26 to protect the joint. Condyles 20 are provided for replacing the condylar surfaces of femur 26 and include spaced outside bearing surfaces 30.
Immediately below femoral component 12 and in sliding contact with both bearing surfaces 30 is tibial platform 13. Tibial platform 13 includes concave upper bearing surfaces 32, of conventional design, that engages bearing surfaces 30 and support condylar elements 20 of femur 26. In the preferred embodiment, tibial platform 13 comprises a single integrally formed body; however, the present invention will also provide force measurement readings for prostheses incorporating two tibial platforms, one supporting each condyle 20 of femoral component 12.
Tibial transducer 14 and cover plate 16 together provide a stationary mounting structure for assembly 10 on a tibia 34. Cover plate 16 is positioned on a tibia plateau 36 resected by conventional surgical procedures. Plateau 36 is flat and normal to the longitudinal axis of tibia 34.
As shown in FIGS. 1 and 2, cover plate 16 comprises a U-shaped support member 37 having a central channel 38. Channel 38 separates two spaced plate sections 40 and 42. Sections 40 and 42 are generally symmetrical with curved, generally circular outer peripheral edges chosen to cover substantially the upper surfaces of tibial plateau 36. Positioned adjacent channel 38 within each plate section 40 and 42 are countersunk apertures 44 and 46. Apertures 44 and 46 receive spikes 48 and 50, which are threaded into transducer 14 and driven into the tibia to align cover plate 16 on plateau 36. Spike 48, shown in detail in FIG. 3, comprises a generally cylindrical body 51 having a downwardly extending conically shaped tip 54. When placed within tibia 34, body 51 and tip 54 extend approximately 1/4 of an inch below the upper surface of plateau 36 with a countersunk mating surface 56 and threaded stud 58 projecting upwardly. In the preferred embodiment, mating surface 56 cooperates with outwardly extending countersunk inner surfaces of apertures 44 and 46, as shown in FIG. 10. Stud sections 58 hold force transducer 14 on cover plate 16 when inserted through apertures 44 and 46 and threaded into threaded apertures 61 in the lower surface 62 of force transducer 14. Additional spikes or other types of anchors, may be provided if additional support is required to secure cover plate 16 to plateau 36.
As shown in the bottom plan view of FIG. 5, transducer 14 is symmetrically U-shaped having a central channel 63 and two spaced sections overlying the sections 40 and 42 of the cover plate 16. A plurality of cavities 64A, 64B, 66A and 66B defining two anterior force responsive flexure sections 74A and 74B, and two posterior force responsive flexure sections 76A and 76B are formed in the transducer 14. Transducer 14 is constructed from suitable elastic material that is responsive to the forces applied between lower surface 62 and an upper surface 92 on transducer 14, shown in FIG. 4, as assembly 10 is articulated.
Anterior cavities 64A and 64B and posterior cavities 66A and 66B are symmetrically positioned on opposite sides of central channel 63. In the preferred embodiment, each cavity is cylindrical with identical radii, having an opening defined into lower surface 62. Each cavity 64A, 64B, 66A and 66B forms a corresponding thin cylindrical flexure member 84A, 84B, 86A and 86B on central body 83, as shown with hidden lines in FIG. 6 in plain view in FIG. 5, and in section in FIGS. 7, 8 and 10.
A plurality of support posts 88A, 88B, 90A and 90B are secured to an upper surface 92 of central body 83 above cavities 64A, 64B, 66A and 66B, respectively. Support post 88A, 88B, 90A and 90B are further secured to a lower surface 93 of an upper plate 94 having the general U-shaped configuration of cover plate 16 and central body 83. The posts 88A, 88B, 90A and 90B are actually integrally formed between body 83 and upper plate 94 by EDM Machining. Forces applied to upper plate 94 are localized and directed through support posts 88A, 88B, 90A and 90B to the corresponding flexure members 84A, 84B, 86A and 86B. As shown for example in FIG. 7, appropriate strain gauges 96, such as resistive strain gauges, are disposed in each cavity on an inner surface 97 of each flexure member. These strain gauges provide a quantitative response to forces applied between upper plate 94 and cover plate 16. Channels 68 and 70, between adjacent cavities, shown in FIG. 5, provide conduits for electrical leads from strain gauges located in posterior cavities 66A and 66B. Channel 72 provides conduit for all electrical leads of the strain gauges with termination on a suitable connector or terminal strip 99. A channel 98 allows associated leads connected to terminal strip 99 to exit transducer 14.
Although force transducer 14 has been described with particular reference to cavities and flexure members formed therein, other types of forces sensors can be used. Such force sensors include semiconductor or piezo-electric sensors formed within or located on a surface of transducer 14. As with the cavities and flexure members discussed above, these force sensors can be displaced laterally on transducer 14 to provide independent force data for various locations.
Transducer 14 is replaceably attached to tibial platform 13 with upper plate 94. As shown in FIGS. 7, 9 and 10, upper plate 94 includes upwardly extending male dovetails 100 formed symmetrically and longitudinally along a central channel 102 of upper plate 94. Dovetails 100 interlock with corresponding female notches 101 in tibial platform 13 shown in FIG. 1. The interlocking relationship of dovetails 100 and notches 101 aligns transducer 14 with tibial platform 13, preventing slippage laterally between the parts.
Referring to FIGS. 4, 6 and 8, channels 104, depressions 106 and aperture 107 formed in upper plate 94 provide additional alignment and a means for locking transducer 14 to tibial platform 13. As shown in FIG. 6, channels 104 extend parallel to central channel 63 to a anterior periphery edge 108. At an inward or rearward end 110, channels 104 curve upwardly to intersect with an upper surface 111 of upper plate 94.
In line with each of channels 104 are corresponding depressions 106. Protruding elements 112 formed on lower surface 113 of tibial platform 13, after being properly aligned with channels 104, exit channels 104 at rearward end 110 and enter depressions 106. Depressions 106 act as detents for protruding elements 112, preventing tibial platform 13 from releasing and sliding relative to transducer 14. Similar protruding elements 115 engage and remain in channels 104. As shown in FIG. 9, aperture 107 in upper plate 94 aligns with a corresponding aperture 113A in tibial platform 13. A pin 109 is inserted within apertures 107 and 113A to interlock tibial platform 13 to transducer 14.
Although the present invention includes a tibial platform replaceably attached between transducer 13 and femoral component 12, alternative embodiments may increase the height of transducer 13, eliminating tibial platform 4 such that transducer 13 directly engages femoral component 12 The thickness of the components can be adjusted for proper fit and comfort.
Use of transducer 14 ensures proper alignment of assembly 10 on the patient. With proper incisions made surrounding the knee joint, femoral component 12 is secured to the patient's femur and the tibia is resected with conventional osteotomy surgical procedures. Force transducer 14 is then attached to tibial platform 13 with protruding elements 115 and 112 interacting with channel 104 and depressions 106, discussed above. Cover plate 16 is secured to transducer 14 with threaded stud portions 58 of spikes 48 and 50. The conical tips and cylindrical bodies of spikes 48 and 50 are then positioned within appropriate apertures drilled normal to the resected tibial plateau.
With all components properly positioned, the knee joint prosthesis is articulated. Forces transferred down the knee joint prosthesis are detected by the strain gauges located within the cavities formed in transducer 14, as discussed above. Electrical signals representative of these applied forces in four separated locations, are then amplified, conditioned, and presented as quantitative data to the surgeon. By monitoring this data, the surgeon determines if balanced loads exist on the prosthetic joint for the partial or full range of articulation. Unequal forces at the four sensing locations can be noted directly, and the total load or force also can be determined. Load inequality from side to side and front to back is determined. If proper force or load distribution is not present, the surgeon can perform curative steps such as additional partial resection of the tibia to make it flat, or at a slightly different angle.
In the preferred embodiment, assembly 10 further comprises a computer 120 electrically connected to transducer 14 as shown schematically in FIG. 11. Computer 120 includes a display 122 capable of presenting individual or combined measured forces applied to the transducer 14 in graphical, numerical or a combined format. Computer 120 stores the quantified data for documentation and analysis purposes. When proper alignment of the joint prosthesis is complete, based on force measurements obtained through transducer 14, transducer 14 is replaced with an appropriate spacer 130 shown in FIG. 12. Spacer 130 is equal in height to transducer 14 with the same general U-shape configuration. Identical dovetails 100, channels 104 and depressions 106 interlock spacer 130 with tibial platform 13. Like transducer 13, cover plate 16 connects to spacer 130 with threaded spikes 48 and 50. After cover plate 16 is affixed securely to the tibia plateau; the incisions are properly sutured; and the patient is taken to the recovery room.
In summary, the present invention provides an assembly and method for implantation of joint prostheses. The assembly measures forces present on the prosthesis in vivo as the joint is articulated through partial or complete range of movements. The resulting data is collected and analyzed to ensure proper force load distribution across the load bearing surfaces of the joint prosthesis. With proper load distribution, the joint prosthesis is optimally aligned thereby realizing increased prosthetic life.
Although the present invention has been described with reference to preferred embodiments, workers 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. | A system is disclosed for measuring dynamically forces applied to a prosthetic joint. The system comprises a first support member attached to an outer surface of a first bone, a second support member attached to an outer surface of a second bone and a transducer secured to the second support member and engaging the first support member. The transducer measures forces applied to the first and second support member as the prosthetic joint is articulated and provides a representative force output signal. In the preferred embodiment, the transducer comprises a central body having plurality of integrally formed flexure members, each flexure member defined by a corresponding cavity in the body and defining a force responsive flexure section. A plate is secured to the transducer with support posts to localize forces onto the flexure members. Although the assembly forms components for implementation of a knee prosthetic, the present invention can be adapted to any particular joint of the body. | 0 |
BACKGROUND OF THE INVENTION
The present invention relates to an unhanded slide latch device.
Slide mechanisms are used in a wide variety of different applications. One common application is to mount a drawer to a supporting member, such as a desk. The interleaved, extensible slide members enable the drawer to be opened and closed with ease. The slide members customarily include latches or stops to prevent the drawer from being opened beyond a given extension.
At times it is desirable to be able to remove the drawer from the supporting structure. For this purpose, a special, releasable slide latch device must be provided. Many such releasable latch devices have been designed and are in use today. For example, one design employs a resilient metallic blade on one slide member that incorporates an opening which receives a stud on an adjacent slide member to limit the travel of the two slide members relative to one another. By depressing the blade, its surface may be caused to clear the stud and the slides moved relative to one another and disconnected. Another releasable latch device employs two cooperating plastic members which have aligned walls such that when one slide member is moved relative to the other sufficiently, the walls engage and prevent further travel of the slide members. A projecting finger on one of the plastic members permits its wall to be moved out of alignment with the wall on the other plastic member, and the slides to be disconnected.
In use, such latch devices should be easily actuated even by this occasional or inexperienced operator. Many applications also require the latch device to be relatively silent; the clank of two metallic surfaces engaging one another is objectionable. Also, many applications require such latch devices to be quite rugged. For example, one common test for drawer slides requires slide mechanisms to withstand both 15,000 two inch travel impacts and five full travel impacts in response to a ten pound pull while the drawer carries a load of 75 pounds.
Since the preferred latch device should be designed to be used in standard constructions of slides, it must also be received between two closely fitting slide members, yet clear the screws, rivets, and other attachment means that connect the slide members to one another, and to the supported members. Finally, the design of the latch device should be such that it can be employed in automated manufacturing operations; this means that, for example, any element which is reversible should work in either orientation.
These and further objects of the invention will appear from in the following detailed description of a preferred embodiment of the unhanded slide latch device.
SUMMARY OF THE INVENTION
The latch device in its preferred form, is designed to limit the longitudinal travel of the two interlocking members, yet to permit these slide members to be disconnected when desired. In its preferred form, the latch device includes a first element that is pivotally attached to one of the slide members, and a second element is attached to the second member in a position such that it lies adjacent to the first element during at least a portion of the longitudinal path of travel of the slide members relative to one another. Each of the two elements includes at least one stop member, located to engage one another as the slide members are moved to bring the elements into an adjacent relationship. Means are included to hold the first element in a normal position, relative to its slide, but to permit to be moved in either of at least two directions, such as clockwise and counter-clockwise, from said normal position sufficiently to displace its stop member from the path of travel of the opposed stop member and to permit the slide member thereby be disconnected.
Preferably the latch device includes cam means to move the first element sufficiently to cause the stops to clear one another when the slide members are being reconnected and interlocked with one another. Also, preferably both elements of the latch device are symmetrical about the longitudinal axis of their slide members. The symmetry is with respect to placement of the interlocking members, not the direction of orientation of the cam means.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be further described in connection with the accompanying drawings, in which:
FIG. 1 is a perspective view showing a drawer received in a desk, only a portion of which is shown;
FIG. 2 is a plan view of the slide assembly shown in FIG. 1 incorporating the unhanded latch device of the present invention;
FIG. 3 is a cross sectional view taken on lines 3--3 of FIG. 2;
FIG. 4 is a cross-sectional view taken on lines 4--4 of FIG. 3;
FIG. 5 is a perspective view of the pivoting latch element of the present invention; and
FIG. 6 is a perspective view of the fixed latch element of the present invention.
DETAILED DESCRIPTION
The unhanded drawer slide latch device of the present invention can be used in a wide variety of slide assemblies employed in any of various applications. For example, it can be incorporated in the slide assembly used to attach a drawer to a supporting structure, such as a cabinet or desk. Such an arrangement is shown in FIG. 1 in which slide assembly 2 attaches drawer 4 to the supporting desk structure 6.
The slide assembly itself is shown in plan view in FIG. 2, and in partial cross-section in FIG. 3. The general construction of such slide assemblies is well known; it is described for example in various United States patents such as U.S. Pats. No. 3,205,025, 3,778,120 or 3,771,849.
In general, slide assemblies consist of an outer, base or cabinet member 10 that receives an intermediate member 12 which in turn supports an inner or drawer member 14. The members of the slide assembly preferably ride over one another on ball bearing assemblies, not shown. The inner member is attached by screws or other suitable devices to the drawer, while the cabinet member is attached to the supporting desk structure. When the drawer is moved relative to the desk, both the inner and intermediate members move relative to one another and to the cabinet member, rolling along the sets of ball bearings carried between them.
Each member of the slide assembly incorporates a stop or latch that is aligned with a corresponding stop or latch on the adjacent member to limit travel of the outer, intermediate and inner members relative to one another, thereby preventing the drawer from being unintentionally removed from the desk. In certain applications, it is desirable to be able to remove the drawer from the supporting structure. This in turn requires use in the slide assembly of cooperating latches that can be selectively disengaged. Such disengagement should be easily effected, even by an inexperienced user. For that reason, the latch device incorporated in the slide assembly should be capable of being disengaged by movement in either direction; it should not be necessary to move the left slide latch device in one direction and the right slide latch device in the opposite direction, for such a requirement has been found to so challenge the inexperienced or occasional operator that they will usually not be successful in effecting disconnection of one slide member from the other.
The preferred embodiment of the latch device of the present invention consists of two elements. The pivoting element 16 is i perspective view in FIGS. 5. The fixed element 18 is shown in perspective view in FIG. 6.
The pivoting element 16 of the latch device, in its preferred embodiment, consists of a planar base portion 20 that includes, at one end, an opening 22 surrounded by an upstanding cylindrical wall 24. Extending along the longitudinal axis of base 20 from the cylindrical wall 24 is an upstanding ridge or rib 26 that projects beyond the base to form a lever or finger 28. Upstanding from the lateral edges of base 20, and extending in a direction generally parallel to rib 26, are stops or walls 30. Two of these walls are provided, one on each side of the rib, the walls being equally spaced from the rib. The function and features of these walls will be described shortly.
The pivoting element 16 also includes a leg 32 extending from base 20 and aligned with rib 26 along the longitudinal axis of the element. This leg, at its inner end, merges into cylindrical wall 24 about opening 22 and, at its outer end, terminates in a ring 34 that incorporates and defines an opening 36 which is slightly elongated in the direction of the longitudinal axis of the element, again for a reason which will be described shortly. The thickness of ring 34 preferably is slightly greater (e.g. 0.015") than the thickness of base 20 of the element for sufficient resiliency to hold the pivoting element in the illustrated orientation. Rib 26 and finger 28 may each include a recess 38 (see FIG. 3) to minimize or eliminate any differential shrinkage and sinkage during cooling, and warpage in base 20.
The fixed element 18 of the latch device, attached to the intermediate member 12 of the slide assembly, is shown in perspective view in FIG. 6. It consists of a generally rectangular body that includes, at each outer end, a cylindrical lobe guide 42. The center portion of the body is raised to form a plateau in area 44. A central opening 46 is provided in this plateau. On either side of the opening, extending in a direction parallel to lobe guides 42, are stops or walls 48. As shown most clearly in FIG. 4, a rivet 50 passes through opening 46 in fixed element 18 and through an opening in the intermediate slide member 12 to attach the element to the slide. The head of this rivet is received in a countersunk recess in opening 46 such that the upper surface of the rivet does not extend beyond the upper surface of plateau 44 between walls 48. The opposed rails of the intermediate slide member pass along the innerfaces of lobe guides 42, as shown in FIG. 4, the lobe guides thereby assisting in positioning and guiding the insertion of the inner slide member relative to the fixed element.
Preferably the fixed element 18 of the latch device also includes a pair of square bosses 52, each generally underlying the trough in element 40 between lobe guide 42 and wall 48, these square bosses being snugly received in openings provided in the intermediate slide member 12 as shown in FIG. 4. In this fashion, the fixed element 18 is attached to the slide by rivet 50; torquing and longitudinal movement of the fixed member relative to the intermediate slide member is resisted by not only the rivet but also by the interlocking of the element with the slide as a result of the square bosses being received in corresponding holes in the intermediate member 12.
As shown in FIG. 3, the pivoting element 16 is attached to the inner slide member by a rivet 54 received in an opening in the inner drawer member. The inner drawer member also includes a short upstanding cylindrical extrusion 56 that is spaced along the longitudinal axis of the inner slide member such that it that it receives ring 34 when the pivoting element 16 is attached to the inner member as shown. The outer diameter of extrusion 56 is slightly smaller than the inner diameter of the opening in ring 34.
Preferably both elements of the latch device are injection molded from a resilient material such as acetal; the pivoting element 16 is Celenese TX-90 and the fixed element 18 is Celenese M-90. Thus, by pressing against lever 28, element 16 may be pivoted about rivet 54 received in opening 22, which in turn flexes leg 32 and causes ring 34 to rotate about the cylindrical extrusion 56 of the intermediate slide member. Since this movement will also pull the ring 34 toward rivet 54, the opening 32 in the ring is elongated slightly to accommodate and permit this longitudinal motion.
When attached to the slide members as shown in FIGS. 3 and 4, the elements of the latch device will engage one another (as best shown in FIG. 4) when the inner slide member is pulled to the limit of its travel relative to the intermediate slide member. Specifically, (and as best shown in FIGS. 5 and 6) the squared face 62 of each wall 30 engages the corresponding squared end 64 of wall 48. The sizing and relationship of the elements of the latch device, as mounted on their respective slide members, is such that solid abutment of these opposed faces is achieved for both walls 30 against walls 48. This results in a definite stop, preventing further movement of the inner slide member relative to the intermediate slide member. Because the abutting elements preferably are made of a plastic material, instead of a metallic material, the click of a metal contact is avoided, which would be objectionable in many slide applications.
It will be noted that both the fixed element and the pivoting element of the latch device are symmetrical about the longitudinal axis of their respective slide members, when mounted as shown in FIGS. 5 and 6. Also, each is attached to its respective slide member along the slide's longitudinal axis. Thus, when the slide members are pulled to the limit of their normal travel, as defined by the abuding relationship of these two latch elements, each face 62 will bear with equal force on the corresponding face 64 of the opposed element, and no net torque will be applied to either the fixed or pivoting element of the latch device.
To disconnect the inner slide member from the intermediate slide member, it is only necessary for the user to press on lever 28. Moving it in either direction, clockwise or counterclockwise about rivet 54, to the point were wall 30 now can clear the normally abutting face of wall 48, will permit the slide members to be separated completely.
To reattach the slide members, it is only necessary to insert the inner slide member into the intermediate slide member, then push the two to a closed position. As they move toward a closed position, inclined faces 70 on walls 30 will engage faces 64 of walls 48. Because both inclined faces 70 slope in the same direction (in parallel planes) relative to walls 48, these faces will cooperate, when they engage the ends of walls 48, to cam the pivoting element 16 about rivet 54 and permit the slide members to continue their travel and be completely nested, one in the other.
Because of the design and construction of the latch device, it may be incorporated in standard slide assemblies without requiring any change in the fitting or slide members of the assembly. The elements of the latch device will clear screw heads used to attach the inner and outer members of the slide assembly to adjacent structures, such as to a desk drawer and a desk frame.
Because both element 30 and element 48 of the latch device are symmetrical about their longitudinal center, the latch device is readily adaptable to automated assembly operations. It has been found, in the preferred construction, the latch device of the present invention is capable of meeting and exceeding the five full travel impacts and 15,000 two inch travel impacts, 75 pound drawer outstop test previously mentioned. This latch device is also "unhanded;" the slide assembly on both sides of the drawer, for example, may be disconnected by pressing lever 28 either up or down. Thus, even inexperienced operators can easily disconnect slides incorporating the latch device of the present invention. Moreover, the drawer member 14 of the left hand slide can be interchanged with drawer member 14 of the right hand slide with no change in function.
Variations in the design and construction of the preferred embodiment of the present invention will undoubtedly occur to those skilled in this art. For example, others may prefer to eliminate ring 34 and to position leg 32 between members punched up from the center portion of the inner slide member, or in an opening in one such member. Thus, the scope of the invention is as set forth in the following claims, interpreted consistent with the principles applicable thereto. | The preferred latch device consists of two elements, attached to interfitting longitudinally movable slide members in a relationship to pass adjacent to one another as the slide members move longitudinally. The elements each carry stops which are positioned to engage one another as the elements come into an adjacent relationship to limit further travel of the slide members. One of the elements is pivotally attached to its slide member, and movable both clockwise and counter clockwise, to displace the stops sufficiently to clear its stops on the other element and permit the slide members to be disconnected. Preferably the rear faces of the stops on one element are sloped in parallel planes to engage the stops on the other element as the slide members are being reconnected, and to cam the pivotal element sufficiently to cause the stops to clear one connection, permitting the slide members to be easily reconnected. | 0 |
Priority is claimed to German Patent Application No. DE 10 2007 055 453.4, filed on Nov. 19, 2007, the entire disclosure of which is incorporated by reference herein.
The present invention relates to a device and a method for laser treatment, in particular for the laser welding of a workpiece, comprising a receiver which carries a laser treatment head and which is configured so as to be displaceable along a linear treatment zone.
BACKGROUND
A device of this type for the laser welding of a workpiece is used for example for the production of moulds for plastics material parts. For example, modern aeroplanes are increasingly manufactured from fiber-reinforced plastics materials. In this case, in comparison with other plastics material components, the components often have very large dimensions, in the range of up to 40 m in length.
However, in comparison with similarly large plastics material components from the field of yacht construction or large containers, there are significantly higher quality requirements for the components. The high quality standards are reflected in the very complex configuration of the moulds which are used for the production of the components. These are subject to a number of constraints:
High form and dimensional stability
Long endurance under cyclical thermal stress in the autoclave
Thermal expansion suited to the plastics material
Low weight
Helium-tightness of the mould surface.
These main requirements are met by a suitable selection of material—in many cases steels with a high proportion of nickel are used—and by an optimized design. The substructure of the actual mould surface is produced from a three-dimensional lightweight sheet metal structure. The actual mould surface on which the fiber-reinforced plastics material component is constructed is then applied to this substructure. The size of the moulds presents the manufacturing companies with serious difficulties, because worldwide, only a few machines are capable of working on workpieces longer than 10 m in one clamp. The dimensions also result in a transport problem. The transport costs escalate as the size increases.
The possibility of segmenting the large moulds, in order to produce individual modules with maximum dimensions suited to the manufacturing capacity of average plants and then to join then by a joining operation at the location where the mould is to be used, has also already been considered. In this case, the joining operation has to meet two basic requirements. On the one hand, the joining operation requires low-heat joining in order to minimize distortions. On the other hand, the gas-tightness of the joined mould must be ensured.
SUMMARY OF THE INVENTION
An aspect of the present invention is to provide a possibility of substantially simplifying the treatment of workpieces of this type. In particular, a time-consuming clamping of the workpiece on a workpiece receiver may be avoided. A further or alternate aspect of the present invention is to provide a method for connecting at least two workpieces, in which undesired effects on the workpieces are largely avoided.
The present invention provides a device for laser welding of a workpiece that includes a laser treatment head, a receiver carrying the laser treatment head and displaceable along a linear treatment zone, and a support configured to be temporarily fixable to the workpiece.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention permits various embodiments. For further clarification of the basic principle of the invention, various of these are described in the following and are shown in the drawings, in which, in each case in a schematic diagram:
FIG. 1 shows a laser treatment head 2 which is arranged so as to be displaceable by means of a mount 20 ;
FIG. 2 shows a device according to the invention with a running gear 6 equipped with a plurality of rollers 5 ;
FIG. 3 shows a further device according to the invention, in which a roller 14 is provided with a circumferential groove 13 ;
FIG. 4 is a plan view of a further device according to the invention, comprising a gateway 16 and a guideway 18 for the displaceable laser treatment head 2 ;
FIG. 5 is a side view of the device shown in FIG. 4 , comprising a scanning unit 21 configured as a distance roller 21 ;
FIG. 6 is a front view of the device shown in FIG. 4 ; and
FIG. 7 shows the device shown in FIG. 4 in an arrangement which is fixed to a workpiece 1 by means of detachable contact surfaces.
DETAILED DESCRIPTION
The invention is described in greater detail in the following with reference to FIG. 1 to 7 . A laser treatment device, configured as a mobile laser system, which makes it possible to work at constant treatment speeds independent of the position and at a constant working distance, is used for welding the workpieces 1 . Various systems can be produced for this purpose. What all these systems have in common is that the guidance and fastening are primarily oriented on the workpiece 1 . This applies in all cases to the distance of the focus point from the treatment zone.
The path of the seam can be retraced in various ways. For example, this may take place in contact with the workpiece 1 by means of tactile sensors, in particular by means of a guide element 8 configured as a guide rail 10 or a correspondingly configured relief 11 on the workpiece 1 . Furthermore, the path of movement can be detected using the data of a previously measured contour.
The systems are also all provided with a sensor system which is capable of adjusting the angular position of the laser beam relative to the surface and producing an angle which is perpendicular to the course of the surface or parallel or perpendicular to gravity, or a desired constant angle. FIG. 1 shows a laser treatment head 2 of this type which is displaceable by means of a mount. In this case, the compensatory movement necessarily always takes place at the point of incidence of the laser.
Another device according to the invention has a running gear 6 provided with a plurality of rollers 5 . This device is an automotive device carrier system. The running gear 6 is preferably provided with three or four rollers 5 and with a motor with a gear unit. The rollers 5 are configured so as to be steerable. The running gear 6 carries additional components, such as a gas inlet and an additional material inlet in particular.
The device may be guided by means of guide rails which are installed on the workpiece 1 , or by means of a guide rail on the workpiece 1 parallel to the joining edge, or by suitable configuration of the joining edge or proximal region, for example by reliefs 11 on the workpiece 1 with one or more ramp surfaces or a guide notch in the plane of the seam.
The laser treatment head 2 is suspended in such a way that any tipping of the laser treatment head 2 takes place about the focus point on the workpiece 1 . This mechanism is coupled to a sensor and a servomotor in such a way that any angle may constantly be maintained, even if the running gear 6 assumes different angles over the course of the surface.
Another device according to the invention, comprising a gateway 16 and a guideway 18 for the displaceable laser treatment head 2 , is shown in FIG. 4 to 7 . This device, which is configured as a mobile multi-axial system, is set up in the vicinity of the treatment zone to connect at least two separate workpieces 1 which are contiguous at a planar joining region 15 . Before the mounting of a spacer disc, a travelling unit carrying the laser treatment head 2 is allowed to hang freely vertical under gravity and then fixed with a clamp in such a way that the angle relative to the surface cannot change. Afterwards, the spacer disc is mounted.
Subsequently, the start and end point or characteristic points such as turning points are approached and the respective positions thereof are stored, by remote control. This takes place with the aid of a camera, which is arranged on the treatment head and projects a target image with crosshairs onto a reproduction screen or an optical display.
The mobile multi-axial system consists of a linear axis providing the portal with at least two stands 17 equipped with support means 5 and a linear axis which serves as a guideway 18 and which provides the rate of feed in the seam direction. The laser treatment head 2 can be deflected in the direction of the main extension of the guideway 18 and also transverse to the main extension. This is permitted by a deflection axis, which allows curves in the path of the seam and is configured for example as an axis of rotation. The device further comprises a spring-loaded, force-loaded or mass-loaded height axis, which is oriented to the contour line of the seam by a distance roller 21 , which is adjustable with respect to the reference position of a laser head.
Other supplementary axes are also possible. In this case, the guideway 18 is preferably configured as a linear axis and the further degrees of freedom are produced by axes of rotation. The gateway 16 is fastened to the workpiece 1 by clamping, magnets or suction devices on the support means 5 . The guideway is configured in such a way that it is possible to treat the workpiece 1 over the whole of the extension thereof.
The treatment can take place on the basis of a treatment programme, in that start and end points are approached and stored and subsequently a linear path, or with a plurality of points a curved path, is determined by means of the control unit 23 . Furthermore, the laser treatment head 2 can be manually displaced by remote control. In this case, with the moulds described, it is usually only necessary to travel linearly. Only two axes are controlled (longitudinal axis and displacement axis). The height axis follows the contour through the spring-loaded disc and thus remains at a constant distance.
It is also possible to let the deflection axis run free and to guide the disc or another guide element in a rail or guideway. Purely manual control via a remote control is also possible.
Additionally, the laser head may be arranged on a suspension means in such a way as to be rotatable, in the angular position thereof to the surface, about the contact point of the point of incidence of the laser on the surface. This angular position can be adjusted using a servomotor, in order to make displacement perpendicular to the surface possible as required.
The same effect can also be achieved by the use of two distance rollers 21 on the positioning means 20 on either side of the treatment zone. It is important in this case that the guide unit is mounted in such a way as to be rotatable on the longitudinal axis and a corresponding suspension means for the laser head is installed and allows the laser treatment head 2 to rotate about the laser contact point.
Both devices may be controlled by an external or internal coordinate measurement system, assisted by radio, radar, ultrasound, laser or satellite transmission.
The shape of the joining region is also of central importance. Depending on the laser welding process and a possible gap between the parts, sinking of the seam surface may occur. In order to achieve subsequent finishing of the surface without the expected sink marks, a small dimension of approximately 1 mm on the joining region is provided as a relief 11 on the workpiece 1 . The width of the relief 11 must be only 3 mm to the left and right of the contact surface. In this way, even in the case of relatively large gaps, a smooth surface can be produced after the finishing, which generally takes place by grinding. The sides of the relief 11 in the joining region may be produced, so as to be accurate to size, on a CNC-system in a clamp.
Deep laser beam welding offers the possibility, when joining a plurality of workpieces 1 , of welding very deep at a low width. Because the energy per unit length used is proportional to the melted cross-sectional area, a significantly lower energy per unit length is applied to the workpiece 1 in this laser process. This means that the distortions are drastically reduced in comparison with the electric arc method.
The joining process is therefore composed of two steps. In the first step, the substructure is joined by mechanical methods and laser welding. In the second step, the mould surface is welded by deep laser beam welding.
Further advantages of the method are:
high process speed (at least 1 m/min)
minimal distortion
apart from the joining region itself, surfaces can be finished
the method can be mechanized
LIST OF REFERENCE NUMERALS
1 Workpiece
2 Laser Treatment Head
3 Receiver
4 Linear Treatment Zone
5 Support Means (e.g., Plurality of Rollers)
6 Running Gear
7 Lead Element
8 Guide Element
9 Recess
10 Guide Rail
11 Linear Relief
12 Probe
13 Circumferential Neck/Groove
14 Roller
15 Planar Joining Region
16 Gateway
17 Stands
18 Guideway
19 Mounting
20 Positioning Means (e.g., Mount)
21 Scanning Unit (e.g., Distance Roller)
22 Parallelogram Guide
23 Control Unit | A device for laser welding of a workpiece includes a laser treatment head, a receiver carrying the laser treatment head and displaceable along a linear treatment zone, and a support configured to be temporarily fixable to the workpiece. | 1 |
TECHNICAL FIELD
The present invention relates to a process for producing microcapsules with a polyurea wall, as well as to the microcapsules themselves and consumer products comprising these microcapsules.
The process of the invention uses 3,5-diamino-1,2,4-triazole as a specific polyamine for forming the wall with the polyisocyanate.
BACKGROUND OF THE INVENTION AND PROBLEM TO BE SOLVED
One of the problems faced by the perfumery industry lies in the relatively rapid loss of the olfactive benefit provided by odoriferous compounds due to their volatility, particularly that of “top-notes”. This problem is generally tackled using a delivery system, e.g. capsules containing a perfume, to release the fragrance in a controlled manner.
Polyurea capsules, formed by polymerisation between a polyisocyanate and a polyamine, are well known capsules that are used in a large variety of technical fields, including perfumery. Guanidine and guanidine salts are commonly used as polyamines in such capsules.
For example U.S. Pat. No. 5,635,211, US 2006/0216509, WO 2007/004166 and WO 2009/153695 all describe microcapsules having walls made of reaction products of guanidine or water-soluble guanidine salts and polyisocyanates or containing such reaction products.
Other polyamines are also used in polyurea microcapsules. For example, U.S. Pat. No. 5,225,118 discloses the use of ethylene diamine, hexamethylene diamine, diethylene triamine, triethylene tetraamine and tetraethylene pentaamine.
However, the olfactive performance of the prior art capsules still needs to be improved. Indeed the hedonic effect perceived by the consumer using a perfumed product, and therefore its perception of the quality of such a product, depends on the olfactive performance of the capsules. It is therefore desirable to provide capsules having a good olfactive performance in diverse products, including both home- and body-care products.
The present invention advantageously solves this problem by providing new polyurea microcapsules having improved olfactive performance in products such as detergents, hair care products and body lotions. Additionally the capsules of the invention have satisfying stability in consumer product bases and are even more stable than prior art capsules made with guanidine in some products, for example hair care products such as hair conditioners. To the best of our knowledge, the present solution to this problem is not described or even suggested in any prior art document.
SUMMARY OF THE INVENTION
The present invention relates to a process for preparing polyurea microcapsules. The invention concerns the capsules themselves as well as perfuming compositions and perfumed articles containing them.
DETAILED DESCRIPTION OF THE INVENTION
One object of the present invention is a process for the preparation of polyurea microcapsules comprising
a) dissolving at least one polyisocyanate comprising at least two isocyanate functional groups in a perfume to form a solution; b) adding to the mixture obtained in step a) an aqueous solution of an emulsifier or of a colloidal stabilizer; c) adding to the mixture obtained in step b) 3,5-diamino-1,2,4-triazole to form a polyurea wall with the polyisocyanate, so as to form a microcapsules slurry;
provided that the process is carried out without any addition of amino acid.
The perfume in which the polyisocyanate is dissolved in step a) can be a perfuming ingredient alone or a mixture of ingredients in the form of a perfuming composition. Any perfuming ingredient or composition can be used. Specific examples of such perfuming ingredients may be found in the current literature, for example in Perfume and Flavour Chemicals, 1969 (and later editions), by S. Arctander, Montclair N.J. (USA), as well as in the vast patent and other literature related to the perfume industry. They are well known to the person skilled in the art of perfuming consumer products, that is, of imparting a pleasant odour to a consumer product.
The perfuming ingredients may be dissolved in a solvent of current use in the perfume industry. The solvent is preferably not an alcohol. Examples of such solvents are diethyl phthalate, isopropyl myristate, Abalyn® (rosin resins, available from Eastman), benzyl benzoate, ethyl citrate, limonene or other terpenes, or isoparaffins. Preferably, the solvent is very hydrophobic and highly sterically hindered, like for example Abalyn®. Preferably the perfume comprises less than 30% of solvent. More preferably the perfume comprises less than 20% and even more preferably less than 10% of solvent, all these percentages being defined by weight relative to the total weight of the perfume. Most preferably, the perfume is essentially free of solvent.
According to a preferred embodiment of the invention, the perfume used in the process of the invention contains less than 10% of its own weight of primary alcohols, less than 15% of its own weight of secondary alcohols and less than 20% of its own weight of tertiary alcohols. Preferably, the perfume used in the process of the invention does not contain any primary alcohols and contains less than 15% of secondary and tertiary alcohols.
According to another preferred embodiment of the invention, there is used an amount of between 25 and 60% of perfume in the process of the invention, these percentages being defined by weight relative to the total weight of the obtained microcapsules slurry.
The polyisocyanates used in the process of the invention comprise at least two isocyanate groups. Preferably they contain at least three isocyanate groups. Following these numbers of functional groups, an optimal reticulation or network of the capsules wall is achieved, providing thus microcapsules exhibiting a prolonged slow release of fragrances, as well as a good stability in the consumer product.
Low volatility polyisocyanates are preferred because of their low toxicity.
The polyisocyanate may be aliphatic, aromatic or a mixture of both aromatic and aliphatic ones. In the case of mixtures of polyisocyanates, each member of the mixture has at least two isocyanate functional groups. Preferably, the at least one polyisocyanate is in the form of a mixture of at least one aliphatic polyisocyanate and of at least one aromatic polyisocyanate, both comprising at least two isocyanate functional groups.
When mixtures of aliphatic and aromatic polyisocyanates according to any of the embodiments of the invention are used in combination with 3,5-diamino-1,2,4-triazole, the olfactive performance and stability of the capsules are optimized.
The term “aromatic polyisocyanate” is meant here as encompassing any polyisocyanate comprising an aromatic moiety. Preferably, it comprises a phenyl, a toluyl, a xylyl, a naphthyl or a diphenyl moiety, more preferably a toluyl or a xylyl moiety. Preferred aromatic polyisocyanates are biurets and polyisocyanurates, more preferably comprising one of the above-cited specific aromatic moieties. More preferably, the aromatic polyisocyanate is a polyisocyanurate of toluene diisocyanate (commercially available from Bayer under the tradename Desmodur® RC), a trimethylol propane-adduct of toluene diisocyanate (commercially available from Bayer under the tradename Desmodur® L75), a trimethylol propane-adduct of xylylene diisocyanate (commercially available from Mitsui Chemicals under the tradename Takenate® D-110N). The chemical structures of these preferred aromatic polyisocyanates are represented in FIG. 1 . In a most preferred embodiment, the aromatic polyisocyanate is a trimethylol propane-adduct of xylylene diisocyanate.
The term “aliphatic polyisocyanate” is defined as a polyisocyanate which does not comprise any aromatic moiety. Preferred aliphatic polyisocyanates are a trimer of hexamethylene diisocyanate, a trimer of isophorone diisocyanate, a trimethylol propane-adduct of hexamethylene diisocyanate (available from Mitsui Chemicals) or a biuret of hexamethylene diisocyanate (commercially available from Bayer under the tradename Desmodur® N 100), among which a biuret of hexamethylene diisocyanate is even more preferred. The chemical structure of this preferred aliphatic polyisocyanate is represented in FIG. 1 .
Examples of preferred specific mixtures of at least one aliphatic polyisocyanate and of at least one aromatic polyisocyanate are a mixture of a biuret of hexamethylene diisocyanate with a trimethylol propane-adduct of xylylene diisocyanate, a mixture of a biuret of hexamethylene diisocyanate with a polyisocyanurate of toluene diisocyanate and a mixture of a biuret of hexamethylene diisocyanate with a trimethylol propane-adduct of toluene diisocyanate. Most preferably, it is a mixture of a biuret of hexamethylene diisocyanate with a trimethylol propane-adduct of xylylene diisocyanate.
In a preferred embodiment, the at least one aliphatic polyisocyanate and the at least one aromatic polyisocyanate are used in a respective molar ratio comprised between 80:20 and 10:90, preferably between 75:25 and 20:80, more preferably between 60:40 and 20:80, even more preferably between 60:40 and 30:70, most preferably between 45:55 and 30:70.
Preferably the polyisocyanate mixture is added in an amount comprised between 2 and 20% by weight, relative to the total weight of the solution obtained in step a).
In step b) of the process of the present invention an aqueous solution of an emulsifier or of a colloidal stabilizer is added to the mixture of step a). In a preferred embodiment, a dispersion or an emulsion is formed wherein droplets of the mixture obtained in step a) are dispersed throughout the aqueous solution of the emulsifier or colloidal stabilizer. For the purpose of the present invention, an emulsion is characterized by the stabilization of the oil droplets by emulsifiers, while in a dispersion the droplets are stabilized by a colloidal stabilizer. The dispersion or emulsion may be prepared by high shear mixing and adjusted to the desired droplet size. Droplet size may be checked with light scattering measurements or microscopy. Preferably an aqueous solution of a colloidal stabilizer is used and therefore a dispersion is formed.
Examples of colloidal stabilizers are polyvinyl alcohol, cellulose derivatives (such as hydroxyethyl cellulose), polyethylene oxide, copolymers of polyethylene oxide and polyethylene or polypropylene oxide, copolymers of acrylamide and acrylic acid or cationic polymers such as for example a cationic copolymer of vinylpyrrolidone and of a quaternized vinylimidazol such as those sold under the trade name Luviquat® (commercially available from BASF). Preferably, the colloidal stabilizer is polyvinyl alcohol or a cationic polymer, which is a copolymer of vinylpyrrolidone and of a quaternized vinylimidazol, or a mixture thereof.
Examples of emulsifiers are anionic surfactants such as sodium dodecyl sulfate or Stepantex® (commercially available from Stepan), non ionic surfactants such as diblock copolymers of polyethylene oxide and polyethylene or polypropylene oxide.
In step c) of the process of the invention, 3,5-diamino-1,2,4-triazole is added. The polyurea wall of the microcapsules is the result of the interfacial polymerisation between the polyisocyanate dissolved in step a) and 3,5-diamino-1,2,4-triazole added in step c).
For the purpose of the present invention, 3,5-diamino-1,2,4-triazole may be used alone, or be admixed with glycerine.
The amount of 3,5-diamino-1,2,4-triazole used is typically adjusted so that, for each mole of isocyanate group dissolved in the perfume of step a), there is added from 0.5 to 3 moles of amine groups in step c). Preferably, for each mole of isocyanate group dissolved in the perfume in step a), 1 to 3, more preferably 1 to 2 moles of amine groups are added in step c).
No specific action is required to induce the polymerisation between the polyisocyanates and 3,5-diamino-1,2,4-triazole. The reaction starts immediately after adding 3,5-diamino-1,2,4-triazole. Preferably the reaction is maintained for 2 to 15 hours, more preferably for 2 to 10 hours.
The specific composition of the polyurea wall is key in obtaining microcapsules that are at the fine balance between release and retention so as to achieve satisfactory release of fragrances, once the capsules are placed for example on textiles or hair, while showing the desired stability in the product base (e.g. counteracts efficiently the extraction of the perfume by the surfactants of the consumer product).
In an optional step of the process of the invention, the microcapsules can be isolated from the slurry. In another optional step, the microcapsules slurry can be dried in a generally known manner to form a polyurea microcapsules powder. Any drying method known to a person skilled in the art can be used and in particular the slurry may be spray dried to provide a microcapsule powder.
The microcapsules obtained by the process of any of the above-described embodiments are also an object of the present invention. Therefore the present invention provides microcapsules comprising
a polyurea wall, which comprises the reaction product of the polymerisation between at least one polyisocyanate comprising at least two isocyanate functional groups and 3,5-diamino-1,2,4-triazole; a colloidal stabilizer or an emulsifier; and an encapsulated perfume;
provided that such capsules do not comprise any amino acid.
According to a preferred embodiment, the polyurea wall is the reaction product of the polymerisation between at least one polyisocyanate and 3,5-diamino-1,2,4-triazole.
The microcapsules obtained have an average diameter (d(v, 0.5)) comprised between 1 and 50 μm and preferably comprised between 5 and 35 μm, more preferably between 5 and 20 μm. In the present context, “average diameter” refers to the arithmetic mean. The present inventors have found that with microcapsules of this size, optimal deposition and/or adherence of microcapsules to the targeted surface, e.g. textile, hair or skin, is obtained.
The polyisocyanate, the perfume and the colloidal stabilizer or emulsifier, as well as the respective amounts of the capsules components, are as defined above in any embodiment related to the process of preparation of the microcapsules.
The microcapsules of the invention can be advantageously used for the controlled release of the encapsulated perfume. It is therefore particularly appreciated to include these microcapsules as perfuming ingredients in a perfumed consumer product.
As shown in the examples below, the polyurea microcapsules obtained by the process of the invention provide particularly good olfactive performance. They provide a controlled release of the encapsulated perfume, said perfume being slowly released from the microcapsules, thus considerably improving the perfume long-lastingness and intensity.
The capsules of the present invention also have the advantage of being stable. More preferably, the microcapsules are considered as stable when not more than 60%, most preferably not more than 50% of the initial perfume load leaks out of the capsules when they are incorporated in a consumer product, for example one of the consumer products listed below, and are stored. The storage time and temperature at which such stability is preferably reached depends on the consumer product type. Preferably, such stability results are reached after 4 weeks storage at 38° C. for home care products such as fabric softeners or detergents, and for body care products such as body wash, deodorants and antiperspirants. In hair-care products such as shampoos and hair conditioners, the storage time and temperature are preferably of at least 2 weeks at 40° C. In very aggressive bases such as body lotions, the storage time and temperature during which such stability is maintained are preferably of at least 2 days at 25° C.
A perfumed consumer product comprising the microcapsules of the invention is therefore also an object of the present invention. In particular the consumer product may be in the form of a home- or personal-care product or in the form of a fine fragrance product. Examples of personal-care products include shampoos, hair conditioners, soaps, body washes such as shower or bath salts, mousses, oils or gels, hygiene products, cosmetic preparations, body lotions, deodorants and antiperspirants. Examples of fine fragrance products include perfumes, after-shave lotions and colognes. Examples of home-care products include solid or liquid detergents, all-purpose cleaners, fabric softeners and refreshers, ironing waters and detergents, softener and drier sheets, among which liquid, powder and tablet detergents and fabric softeners are preferred. As detergents we include here products such as detergent compositions or cleaning products for washing up or for cleaning various surfaces, for example intended for the treatment of textiles or hard surfaces (floors, tiles, stone-floors, etc). Preferably the surface is a textile or skin.
Particularly preferred consumer products include powder and liquid detergents, fabric softeners, body wash, deodorants and antiperspirants, most preferably roll-on deodorants and antiperspirants, hair shampoo, hair conditioners and body lotions. Most preferred ones are powder and liquid detergents, body lotions and hair care products, such as shampoos.
The capsules slurry obtained in the process of the invention may be used as such to perfume the consumer products, in which case the reaction mixture is directly added to a consumer product as defined in any of the above embodiments. Alternatively, the microcapsules obtained in the process of the invention may be isolated from the reaction mixture before being incorporated into the consumer product. Similarly, the reaction mixture comprising the microcapsules of the invention may be mixed with or sprayed onto a dry, powdered product, such as a washing powder or powdered detergent or the microcapsules may be dried and added to these products in solid form. The microcapsules may for example be spray-dried.
Preferably, the consumer product comprises from 0.01 to 10%, more preferably from 0.05 to 2% of the microcapsules of the present invention, these percentages being defined by weight relative to the total weight of the consumer product. Of course the above concentrations may be adapted according to the olfactive effect desired in each product.
Formulations of consumer product bases in which the microcapsules of the invention can be incorporated can be found in the abundant literature relative to such products. These formulations do not warrant a detailed description here, which would in any case not be exhaustive. The person skilled in the art of formulating such consumer products is perfectly able to select the suitable components on the basis of his general knowledge and of the available literature. In particular, examples of such formulations can be found in the patents and patent applications relative to such products, for example in WO 2008/016684 (pages 10 to 14), in US 2007/0202063 (paragraphs [0044] to [0099]), in WO 2007/062833 (pages 26 to 44), in WO 2007/062733 (pages 22 to 40), in WO 2005/054422 (pages 4 to 9), in EP 1741775, in GB 2432843, in GB 2432850, in GB 2432851 or in GB 2432852.
DESCRIPTION OF THE DRAWINGS
FIG. 1 : Chemical structures of 3,5-diamino-1,2,4-triazole and some examples of polyisocyanates that can be used in the present invention.
EXAMPLES
The following examples are further illustrative of the present invention embodiments, and further demonstrate the advantages of the invention capsules relative to prior art teachings.
Example 1
Preparation of Polyurea Microcapsules of the Invention
Polyurea microcapsules according to the invention (Capsules A) were prepared having the following ingredients.
TABLE 1
Composition of Capsules A
Amount
Molar percentage,
Ingredient
[g]
relative to total polyisocyanate
Desmodur ® N 100 1)
12.0
45
Takenate ® D-110N 2)
28.1
55
Perfume 3)
400.0
—
Polyvinyl alcohol 4)
5.5
—
Tetraethyl ammonium chloride 5)
4.0
—
3,5-diamino-1,2,4-triazole 6)
6.9
—
Water
562.5
1) Biuret of hexamethylene diisocyanate, origin: Bayer
2) Trimethylol propane-adduct of xylylene diisocyanate, origin: Mitsui Chemicals
3) Perfuming composition of Table 1a
TABLE 1a
Composition of the perfume
Amount
Ingredient
LogP
[%]
Allyl (cyclohexyloxy)-acetate a)
2.72
1.2
2,4-Dimethyl-3-cyclohexene-1-carbaldehyde b)
2.85
1.2
Menthone
2.87
1.7
Hedione ® c)
2.98
5.8
Camphor
3.04
2.9
Eucalyptol
3.13
5.8
Dihydromyrcenol d)
3.47
11.5
Rose oxyde
3.58
0.9
Isobornyl acetate
3.86
11.5
Delta damascone
4.13
0.6
Cashmeran ® e)
4.31
2.3
Terpenyl acetate
4.34
5.8
Lilial ® f)
4.36
17
Linalyl acetate
4.39
2.3
Neobutenone ® alpha g)
4.45
1.2
Dihydromyrcenyl acetate
4.47
2.3
2-Methylundecanal
4.67
3.5
Iso E Super ® h)
4.71
11.5
Cetalox ® i)
4.76
0.6
Isoraldeine ® 70 j)
4.84
2.3
Habanolide ® k)
4.88
4.6
Precyclemone B l)
5.18
3.5
Total
100.0
a) Origin: Dragoco, Holzminden, Germany
b) Origin: Firmenich SA, Geneva, Switzerland
c) Methyl dihydrojasmonate, origin: Firmenich SA, Geneva, Switzerland
d) Origin: International Flavors & Fragrances, USA
e) 1,2,3,5,6,7-Hexahydro-1,2,3,3-pentamethyl-4h-inden-4-one, origin: International Flavors & Fragrances, USA
f) 3-(4-Tert-butylphenyl)-2-methylpropanal, origin: Givaudan SA, Vernier, Switzerland
g) 1-(5,5-Dimethyl-1-cyclohexen-1-yl)-4-penten-1-one, origin: Firmenich SA, Geneva, Switzerland
h) 1-(Octahydro-2,3,8,8-tetramethyl-2-naphtalenyl)-1-ethanone, origin: International Flavors & Fragrances, USA
i) Dodecahydro-3a,6,6,9a-tetramethyl-naphtho[2,1-b]furan, origin: Firmenich SA, Geneva, Switzerland
j) 3-Methyl-4-(2,6,6-trimethyl-2cyclohexen-1-yl)-3-buten-2-one, origin: Givaudan SA, Vernier, Switzerland
k) Pentadecenolide, origin: Firmenich SA, Geneva, Switzerland
1) 1-Methyl-4-(4-methyl-3-pentenyl)cyclohex-3-ene-1-carboxaldehyde, origin: International Flavors & Fragrances, USA
4) Mowiol ® 18-88, origin: Fluka
5) Tetraethyl ammonium chloride (50% aqueous solution), origin: Fluka
6) Origin: Alfa Aesar
The Desmodur® N 100 and the Takenate® D-110N were dissolved in the perfume. This oil phase was introduced in a one liter glass double-jacketed reactor equipped with a scrapped stirrer and an Ika-rotor/stator system (6500-24000 rpm). The oil phase was stirred at 50 rpm with the scrapped stirrer for 5 minutes.
An aqueous stabilizer solution at 1% by weight, relative to the total weight of the stabilizer solution, was prepared by dissolving the polyvinyl alcohol in 543.5 g of deionised water. This solution was introduced into the reactor at room temperature and the scrapped stirrer was stopped.
A pre-emulsion was then prepared by dispersing the perfume phase in the aqueous phase with the Ika-rotor/stator system during 10 minutes at 13500 rpm.
Once the emulsion was prepared, the stirring was continued with the scrapped stirrer at 200 rpm till the end of the process.
The tetraethyl ammonium chloride solution was added to the emulsion. Then, a solution of the 3,5-diamino-1,2,4-triazole in 19 g of deionised water was added to the reactor over one hour. The temperature of the reaction mixture was kept at room temperature for two hours. The perfume content in the capsules suspension was around 40%, relative to the total weight of the suspension.
Example 2
Preparation of Polyurea Microcapsules of the Invention
Capsules B to D were prepared using the method described in Example 1. The respective amount of Desmodur® N 100 and Takenate® D-110N varied for each of these capsules as summarized in the table below.
TABLE 2
Amounts of polyisocyanates in Capsules B to D
Amount Desmodur ®
Amount Takenate ®
N 100 1)
D-110N 2)
[g]
[g]
Capsules B
26.7
0.0
Capsules C
0.0
51.1
Capsules D
8.0
35.8
1) Biuret of hexamethylene diisocyanate, origin: Bayer
2) Trimethylol propane-adduct of xylylene diisocyanate, origin: Mitsui Chemicals
Example 3
Comparative
Preparation of Polyurea Microcapsules Comprising Guanidine Carbonate as Polyamine
Comparative capsules (Controls A to C) were prepared as described in Examples 1 and 2, except that 9 g of guanidine carbonate (origin: Arcos Organics) was used instead of the 3,5-diamino-1,2,4-triazole. The types and amounts of polyisocyanates in Controls A, B and C were the same as in Capsules A, B and C, respectively.
Example 4
Average Diameter of the Capsules of the Invention
The size distribution of the Capsules A to D was controlled by Optical Microscopy and Light Scattering (Mastersizer S, Malvern) and the average diameter was calculated (arithmetic mean) for each type of capsules. The results are summarized in the following table.
TABLE 3
Average diameter of Capsules A to D
Average diameter
Capsules of the
d(v, 0.5)
invention
[μm]
Capsules A
5
Capsules B
5
Capsules C
5
Capsules D
5
Example 5
Preparation of a Fabric Softener Comprising the Polyurea Microcapsules of the Invention
A concentrated unperfumed fabric softener base was prepared by admixing the ingredients listed in Table 4, in the amounts indicated. The percentages are defined by weight relative to the total weight of the unperfumed fabric softener base.
TABLE 4
Formulation of the concentrated unperfumed fabric softener base
Ingredient
%
Stepantex ® VL90 A Diester Quat 1)
16.50
Proxel GXL 2)
0.04
CaCl 2 (10% aqueous solution)
0.20
Water
83.26
1) Origin: Stepan
2) Origin: Avecia
Softeners A to D were prepared by adding Capsules A to D at 1.26% by weight, relative to the total weight of the softener, under gentle shaking into the unperfumed softener base of Table 4.
Example 6
Stability of the Polyurea Microcapsules of the Invention in a Fabric Softener Base
The storage stability of the capsules in Softeners A, C and D was evaluated. The softeners comprising the capsules were stored during one month at 38° C. and the amount of perfume having leaked out of the capsules was measured by solvent extraction and GC-MS analysis. The results are summarized in the following table.
TABLE 5
Storage stability of the capsules in Softeners A, C and D
Fabric
Amount of perfume that
softener of the
leaked out of the capsules
invention
[%]
Softener A
11
Softener C
5
Softener D
8
The capsules of the invention are therefore stable in a fabric softener base.
Example 7
Preparation of a Concentrated Liquid Detergent Comprising the Polyurea Microcapsules of the Invention
Liquid Detergents A to D were prepared by mixing Capsules A to D at 0.275% by weight, relative to the total weight of the detergent with the commercially available unperfumed concentrated liquid detergent base Tide® 2×HE Free of perfume and dye (trademark of Procter and Gamble, USA).
Example 8
Comparative
Preparation of a Concentrated Liquid Detergent Comprising the Polyurea Microcapsules of Example 3
Control Liquid Detergents A to C were prepared by mixing Controls A to C at 0.275% by weight, relative to the total weight of the detergent with the commercially available unperfumed concentrated liquid detergent base Tide® 2×HE Free of perfume and dye (trademark of Procter and Gamble, USA).
Example 9
Olfactive Performance of the Polyurea Microcapsules of the Invention in Concentrated Liquid Detergent
The olfactive performance of Capsule A, as well as that of Control A was then evaluated in the corresponding concentrated liquid detergents of Examples 7 and 8.
Fabrics (2.5 kg of cotton terry towels) were washed at 40° C. in a standard European horizontal axis machine. There were dispensed 80 g of freshly prepared detergent at the start of the wash through the detergent drawer. After the wash, fabrics were line-dried and the odour intensity of the cotton towels was evaluated by a panel of 20 trained panelists, after 1 day drying. The panelists were asked to rate the odour intensity of the towels after gentle rubbing of the fabrics by hand on a scale from 1 to 7, 1 corresponding to odorless and 7 corresponding to a very strong odour. The results are shown in Table 6.
TABLE 6
Olfactive performance of Capsule A and of Control A in
concentrated liquid detergent
Olfactive
Capsule
performance of the
Olfactive
of the
capsules of the
performance of the
Corresponding
invention
invention
Control
Control
Capsules A
4.6
4.2
Control A
It is clear from these results that, after rubbing, the perfume intensity was more intense on fabrics washed with the liquid detergent containing the capsules of the invention, than on fabrics washed with the liquid detergent containing the control capsules.
Therefore, the perfume is perceived more intensely when the capsules are made with 3,5-diamino-1,2,4-triazole than when they are made with guanidine carbonate.
Example 10
Stability of the Polyurea Microcapsules of the Invention in a Concentrated Liquid Detergent
The storage stability of the capsules in Liquid Detergents A, C and D was evaluated. The detergents comprising the capsules were stored during four weeks at 38° C. and the amount of perfume having leaked out of the capsules was measured by solvent extraction and GC-MS analysis. The results are summarized in the following table.
TABLE 7
Storage stability of the capsules of the invention in
Liquid Detergents A, C and D
Amount of perfume that
Liquid detergent of
leaked out of the capsules
the invention
[%]
Liquid Detergent A
26
Liquid Detergent C
9
Liquid Detergent D
19
It is apparent from these results that the capsules of the present invention are stable in the concentrated liquid detergent base.
Example 11
Preparation of a Concentrated Powder Detergent Comprising the Polyurea Microcapsules of the Invention
Powder Detergents A to D were prepared by mixing Capsules A to D at 0.275% by weight, relative to the total weight of the detergent into the commercially available unperfumed concentrated powder detergent base Ultra Tide® Free and Gentle (trademark of Procter and Gamble, USA).
Example 12
Comparative
Preparation of a Concentrated Powder Detergent Comprising the Polyurea Microcapsules of Example 3
Control Powder Detergents A to C were prepared by adding Controls A to C at 0.275% by weight, relative to the total weight of the detergent into the commercially available unperfumed concentrated powder detergent base Ultra Tide® Free and Gentle (trademark of Procter and Gamble, USA).
Example 13
Olfactive Performance of the Polyurea Microcapsules of the Invention in Concentrated Powder Detergent
The olfactive performance of Capsules A and B as well as that of Controls A and B was then evaluated in the corresponding concentrated powder detergents of Examples 11 and 12.
Fabrics (2.5 kg of cotton terry towels) were washed at 40° C. in a standard European horizontal axis machine. There were dispensed 50 g of freshly prepared detergent at the start of the wash through the detergent drawer. After the wash, fabrics were line-dried and the odour intensity of the cotton towels was evaluated by a panel of 20 trained panelists, after 1 day drying. The panelists were asked to rate the odour intensity of the towels after gentle rubbing of the fabrics by hand on a scale from 1 to 7, 1 corresponding to odorless and 7 corresponding to a very strong odour. The results are shown in Table 8.
TABLE 8
Olfactive performance of Capsules A and B and of
Controls A and B in concentrated powder detergent
Olfactive
Capsule
performance of the
Olfactive
of the
capsules of the
performance of the
Corresponding
invention
invention
Control
Control
Capsules A
4.6
4.2
Control A
Capsules B
3.0
3.0
Control B
It is clear from these results that, after rubbing, the perfume intensity was more intense on fabrics washed with the powder detergent containing the capsules of the invention, than on fabrics washed with the powder detergent containing the control capsules.
Therefore, the perfume is perceived more intensely when the capsules are made with 3,5-diamino-1,2,4-triazole than when they are made with guanidine carbonate.
Example 14
Preparation of a Body Wash Comprising the Polyurea Microcapsules of the Invention
A body wash formulation was prepared by admixing the ingredients listed in Table 9, in the amounts indicated. The percentages are defined by weight relative to the total weight of the body wash formulation.
TABLE 9
Composition of the body wash formulation
Ingredient
Amount [%] w/w
Carbopol ® Aqua CC polymer 1)
8.0
Citric acid (40% solution in water)
0.5
Zetesol AO 328 U 2)
25.0
Tego Betain F 50 3)
4.0
Glydant Plus Liquid 4)
0.1
Sodium Chloride (20% solution in water)
4.0
Water
58.4
1) Polyacrylate-1 crosspolymer, origin: Noveon
2) Sodium C 12 -C 15 pareth sulfate, origin: Zschimmer & Schwarz
3) Cocamidopropyl betaine, origin: Goldschmidt AG
4) DMDM hydantoin and iodopropynyl butylcarbamate, origin: Lonza
Body Washes A to D were prepared by mixing Capsules A to D at 0.5% by weight, relative to the total weight of the body wash into the body wash formulation prepared above.
Example 15
Stability of the Polyurea Microcapsules of the Invention in a Body Wash Base
The storage stability of the capsules in Body-Washes A to D was evaluated. The body-washes were stored for 4 weeks at 45° C. and the amount of perfume having leaked out of the capsules was measured by SPME and GC-MS analysis. The results are summarized in the following table.
TABLE 10
Storage stability of the capsules of the invention
in Body-Washes A to D
Amount of perfume
Body-Wash
that leaked out of the
of the invention
capsules [%]
Body-Wash A
3
Body-Wash B
16
Body-Wash C
4
Body-Wash D
3
It is apparent from these results that the capsules of the present invention are stable in the body wash base.
Example 16
Preparation of a Roll-on Antiperspirant Deodorant Product Comprising the Polyurea Microcapsules of the Invention
A roll-on antiperspirant deodorant emulsion formulation was prepared by admixing the ingredients listed in Table 11, in the amounts indicated. The percentages are defined by weight relative to the total weight of the roll-on antiperspirant deodorant formulation.
TABLE 11
Composition of the roll-on antiperspirant
deodorant formulation
Ingredient
Amount [%] w/w
Brij 72 1)
3.25
Brij 721 2)
0.75
Arlamol E 3)
4.00
Locron L 4)
40.00
Water
52.00
1) Origin: Croda
2) Origin: Croda
3) Origin: Croda
4) Origin: Clariant
Deodorants A to D were prepared by mixing Capsules A to D at 1.26% by weight, relative to the total weight of the roll-on antiperspirant deodorant into the roll-on antiperspirant deodorant emulsion formulation prepared above.
Example 17
Stability of the Polyurea Microcapsules of the Invention in a Roll-on Antiperspirant Deodorant
The storage stability of the capsules in Deodorants A to D was evaluated. The deodorants were stored for 4 weeks at 45° C. and the amount of perfume having leaked out of the capsules was measured by SPME and GC-MS analysis. The results are summarized in the following table.
TABLE 12
Storage stability of the capsules of
the invention in Deodorants A to D
Amount of perfume
Deodorant of the
that leaked out of the
invention
capsules [%]
Deodorant A
10
Deodorant B
55
Deodorant C
7
Deodorant D
7
It is apparent from these results that the capsules of the present invention are stable in the roll-on antiperspirant deodorant base.
Example 18
Preparation of a Hair Shampoo Comprising the Polyurea Microcapsules of the Invention
A hair shampoo formulation was prepared by admixing the ingredients listed in Table 13, in the amounts indicated. The percentages are defined by weight relative to the total weight of the hair shampoo formulation.
TABLE 13
Composition of the hair shampoo formulation
Ingredient
Amount [%] w/w
Jaguar C-14S 1)
0.4
Dehyton AB-30 2)
7.0
Texapon NSO IS 3)
45.0
Dow Corning 2-1691 emulsion
3.0
Cutina AGS 4)
0.9
Rewomid IPP 240 5)
1.2
Cetyl alcohol
1.2
Glydant plus liquid 6)
0.3
Water
41.0
1) Origin: Rhodia
2) Origin: Cognis
3) Origin: Cognis
4) Origin: Cognis
5) Origin: Degussa
6) Origin: Lonza
Shampoos A to D were prepared by mixing Capsules A to D at 0.5% by weight, relative to the total weight of the shampoo into the hair shampoo formulation prepared above.
Example 19
Comparative
Preparation of a Hair Shampoo Comprising the Polyurea Microcapsules of Example 3
Control Shampoos A to C were prepared by adding Controls A to C at 0.5% by weight, relative to the total weight of the hair shampoo into the hair shampoo formulation prepared in Example 18.
Example 20
Olfactive Performance of the Polyurea Microcapsules of the Invention in Hair Shampoo
The olfactive performance of Capsules A to C as well as that of Controls A to C was then evaluated in the corresponding hair shampoo of Examples 18 and 19.
A 10 g hair swatch was first washed with 2.5 g of the shampoo, rinsed for 30 seconds under tap water at 37° C. before repeating the same wash/rinse operation a second time. The hair swatch was then left to dry for 6 hours at room temperature before evaluating.
The intensity of the perception of the perfume on the hair swatches washed with the shampoos was evaluated by a panel of 10 trained panelists. They were asked to comb gently the hair swatches 3 times and then to rate the intensity of the perfume perception on a scale ranging from 1 to 7, wherein 1 means no odour and 7 means very strong odour.
TABLE 14
Olfactive performance of Capsules A to C and
of Controls A to C in hair shampoo
Olfactive
Capsule
performance of the
Olfactive
of the
capsules of the
performance of the
Corresponding
invention
invention
Control
Control
Capsules A
3.2
2.8
Control A
Capsules B
2.9
2.6
Control B
Capsules C
2.6
2.5
Control C
It is clear from these results that, after rubbing, the perfume intensity was more intense on hair washed with the shampoo containing the capsules of the invention, than on hair washed with the shampoo containing the control capsules.
Therefore, the perfume is perceived more intensely when the capsules are made with 3,5-diamino-1,2,4-triazole than when they are made with guanidine carbonate.
Example 21
Stability of the Polyurea Microcapsules of the Invention in a Hair Shampoo
The storage stability of the capsules in Shampoos A to D was evaluated. The hair shampoos were stored for 2 weeks at 40° C. and the amount of perfume having leaked out of the capsules was measured by SPME and GC-MS analysis. The results are summarized in the following table.
TABLE 15
Storage stability of the capsules of
the invention in Shampoos A to D
Amount of perfume
Shampoo of the
that leaked out of the
invention
capsules [%]
Shampoo A
6
Shampoo B
27
Shampoo C
3
Shampoo D
5
It is apparent from these results that the capsules of the present invention are stable in the hair shampoo base.
Example 22
Preparation of a Rinse-Off Hair Conditioner Comprising the Polyurea Microcapsules of the Invention
Rinse-off hair conditioners (herein after Rinse-Off) A to D were prepared by mixing Capsules A to D at 0.5% by weight, relative to the total weight of the rinse-off hair conditioner into the commercially available Pantene® rinse-off hair conditioner formulation (trademark of Procter and Gamble, USA).
Example 23
Stability of the Polyurea Microcapsules of the Invention in a Rinse-Off Hair Conditioner Base
The storage stability of the capsules in Rinse-Off A, C and D was evaluated. The rinse-off comprising the capsules were stored during two weeks at 40° C. and the amount of perfume having leaked out of the capsules was measured by solvent extraction and GC-MS analysis. The results are summarized in the following table.
TABLE 16
Storage stability of the capsules of
the invention in Rinse-off A, C and D
Amount of perfume that
Rinse-off of the
leaked out of the capsules
invention
[%]
Rinse-off A
53
Rinse-off C
25
Rinse-off D
39
It is apparent from these results that the capsules of the present invention are stable in the rinse-off hair conditioner base.
Example 24
Preparation of a Leave-on Hair Conditioner Comprising the Polyurea Microcapsules of the Invention
A leave-on hair conditioner formulation was prepared by admixing the ingredients listed in Table 17, in the amounts indicated. The percentages are defined by weight relative to the total weight of the leave-on hair conditioner formulation.
TABLE 17
Composition of the leave-on hair conditioner formulation
Ingredient
Amount [%] w/w
Water
95.5
Mirasil ADM-E 1)
1.5
Salcare SC 91 2)
1.0
Aculyn 46 3)
1.0
Wacker-Belsil DMC 6038 4)
0.5
Phenonip 5)
0.5
1) Origin: Rhodia
2) Origin: Ciba
3) Origin: Rohm & Haas
4) Origin: Wacker
5) Origin: Clariant
Leave-On Hair Conditioners (herein after Leave-On) A to D were prepared by mixing Capsules A to D at 0.26% by weight, relative to the total weight of the leave-on hair conditioner into the leave-on hair conditioner formulation prepared above.
Example 25
Comparative
Preparation of a Leave-on Hair Conditioner Comprising the Polyurea Microcapsules of Example 3
Control Leave-On Hair Conditioners (herein after Leave-On) A to C were prepared by adding Controls A to C at 0.26% by weight, relative to the total weight of the leave-on hair conditioner into the leave-on hair conditioner formulation prepared in Example 24.
Example 26
Stability of the Polyurea Microcapsules of the Invention in a Leave-on Hair Conditioner Base
The storage stability of the capsules in Leave-on A to D and in control Leave-on A to C was evaluated. The leave-on hair conditioners comprising the capsules were stored during two weeks at 45° C. and the amount of perfume having leaked out of the capsules was measured by solvent extraction and GC-MS analysis. The results are summarized in the following table.
TABLE 18
Storage stability of the capsules of
the invention in Leave-on A to D
Amount
Amount of
of perfume
perfume that
that leaked
leaked out
Leave-On of
out of the
of the control
Control
the invention
capsules [%]
capsules [%]
Leave-On
Leave-On A
7
18
Control A
Leave-On B
54
73
Control B
Leave-On C
5
7
Control C
Leave-On D
8
It is apparent from these results that the capsules of the present invention are more stable in the concentrated leave-on hair conditioner base than the corresponding controls made with guanidine.
Example 27
Preparation of a Body Lotion Comprising the Polyurea Microcapsules of the Invention
Body Lotions A to D were prepared by dispersing Capsules A to D at 1.25% by weight, relative to the total weight of the body lotion into a commercially available body lotion formulation (Bath & Body Work, USA).
Example 28
Comparative
Preparation of a Body Lotion Comprising the Polyurea Microcapsules of Example 3
Control Body Lotions A to C were prepared by dispersing Capsules A to C at 1.25% by weight, relative to the total weight of the body lotion into a commercially available body lotion formulation (origin: Bath & Body Work, USA).
Example 29
Olfactive Performance of the Polyurea Microcapsules of the Invention in Body Lotion
The olfactive performance of Capsules A to C as well as that of Controls A to C was then evaluated in the corresponding body lotions of Examples 27 and 28.
An amount of 0.15 g of each body lotion was spread on a paper blotter (4.5 cm*12 cm) and left to dry for 1 hour at room temperature before evaluating.
The intensity of the perception of the perfume on the blotters treated with the above body-lotions was evaluated by a panel of 10 trained panelists. They were asked to rub gently the blotters with one finger and then to rate the intensity of the perfume perception on a scale ranging from 0 to 10, wherein 0 means no odour and 10 means very strong odour. The results are summarized in the following table.
TABLE 19
Olfactive performance of Capsules A to C and
of Controls A to C in body lotion
Olfactive
Capsule
performance of the
Olfactive
of the
capsules of the
performance of the
Corresponding
invention
invention
Control
Control
Capsules A
8.0
7.0
Control A
Capsules B
7.0
6.1
Control B
Capsules C
7.5
5.3
Control C
It is clear from these results that, after rubbing, the perfume intensity was more intense on blotters treated with the body lotion containing the capsules of the invention, than on blotters treated with the body lotion containing the control capsules.
Therefore, the perfume is perceived more intensely when the capsules are made with 3,5-diamino-1,2,4-triazole than when they are made with guanidine carbonate.
Example 30
Stability of the Polyurea Microcapsules of the Invention in a Body Lotion
The storage stability of the capsules in Body Lotions A, C and D was evaluated. The body lotions were stored for 2 days at 25° C. and the amount of perfume having leaked out of the capsules was measured by SPME and GC-MS analysis. The results are summarized in the following table.
TABLE 20
Storage stability of the capsules of
the invention in Body Lotions A, C and D.
Amount of perfume
Body Lotion of the
that leaked out of the
invention
capsules [%]
Body Lotion A
15
Body Lotion C
4
Body Lotion D
8
It is apparent from these results that the capsules of the present invention are stable in the body lotion base. | The present invention relates to a process for producing microcapsules with a polyurea wall, as well as to the microcapsules themselves and consumer products comprising these microcapsules. The process of the invention uses 3,5-diamino-1,2,4-triazole as a specific polyamine for forming the wall with the polyisocyanate. | 1 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a golfclub, and more particularly to a "wood" type golfclub head structure made of stainless steel.
2. Prior Art
Ever since the beginning of golf history, there have been recognized two types of golfclubs; one is called "iron" clubs which have a relatively short shaft with a small "iron" head designed to hit a golf ball accurately and the other is called "wood" clubs which have a relatively long shaft with a large "wood" head designed to hit a ball for a longer distance.
The head portion of the "wood" clubs is traditionally made of solid wood block. Until recently, persimmon was considered to be the most desirable material because of its high impact resistance and fine sound effect. In addition, golfers favored the well-balanced configuration of the traditional persimmon club heads. Particularly, the smooth tapered line in its neck portion has been highly appreciated. With these and other reasons, persimmon wood clubs substantially predominated the market for a long time.
However, as the demand for good persimmon material grew, the natural source of persimmon became scarce. As a result manufactorers find it rather difficult to satisfy all the market. In an attempt to meet the growing market demand, a number of suggestions and proposals have been made in terms of substitute for natural persimmon.
By way of example, U.S. Pat. No. 3,591,183 discloses a laminated golfclub head which is constructed of wood lamination bonded together and bent to form the angle between striding portion and hosel. U.S. Pat. No. 4,204,684 teaches the use of acrylonitrilebutadiene-styrene (ABS) and other plastic materials. U.S. Pat. No. 4,326,716 discloses a clubhead made of vulcanized polyurethane. In addition, steel made "wood" clubs have been disclosed by U.S. Pat. Nos. 3,761,095, 4,021,047, 4,139,196, 4,214,754, 4,319,752 and many others.
Among these substitute materials, stainless steel has recently acquired a significant part of the marketplace.
In general, a stainless steel "wood" club has a clubhead made of stainless steel having a basic shape similar to the conventional persimmon wood club. Its head portion includes an enclosed hollow body defining a hitting surface, a top wall, a sole member, side walls and a neck.
It has been recognized that stainless steel has certain advantages over natural persimmon, such as lower material cost, durability, and less complex finishing process. However, it has been noticed that stainless steel suffers from some disadvantages.
The most critical problem of stainless steel as a substitute for persimmon exists in its weight balance.
Stainless steel is relatively heavy in nature. Thus, it is necessary to have the walls very thin in order to maintain the same total weight as a persimmon head. On the other hand, it is required to have certain thickness to secure sufficient impact resistance and durability. In particular, since the neck portion has been considered to be weak (see U.S. Pat. No. 4,326,716, col. 2, lines 44 and 45), there is a limit to reduce the thickness of the neck portion. As a consequence, the side adjacent to the neck portion (called "heel") tends to have more weight than the other side ("toe"). This causes the center of gravity (sweet-spot) to shift toward the heel side resulting in more deflection in hitting a ball.
The existing solutions to this problem are to have the whole head portion substantially smaller than the traditional persimmon club and/or to have a straight cylindrical neck portion with its lower portions flared to be connected to the head portion as shown FIG. 1. The above solutions have cured the problem to an extent; nonetheless, those solutions have failed to construct a "wood" club head having the size and the configuration which golfers have been enjoying with the traditional persimmon heads.
Therefore, the existing stainless steel "wood" clubs have not superseded qualified persimmon wood clubs.
SUMMARY OF THE INVENTION
Accordingly, it is the primary object of this invention to provide a stainless steel "wood" club which overcomes the disadvantages contained in the prior art stainless steel "wood" clubs.
It is another object of this invention to provide a stainless steel "wood" club which has the sweet-spot in the center of the hitting surface keeping the traditional size and shape in the head portion.
It is still another object of this invention to provide a stainless steel "wood" club which is easy to play and easy to manufacture.
In keeping with the priciples of this invention, the objects are accomplished by a unique structure of the body and the neck portion of the clubhead, wherein the improvement includes the following features:
(a) the neck has a shoulder at its lower end,
(b) the neck has a cylindrical portion extending upwardly from said shoulder,
(c) the cylindrical portion has relatively thin and substantially even thickness in its wall,
(d) a radius is provided between the cylindrical portion and the shoulder,
(e) another radius is provided between the shoulder and the inside of the body,
(f) a shaft is fitted into the cylindrical portion, and
(g) a plastic ferrule is mounted around the cylindrical portion such that the ferrule stands on the shoulder.
BRIEF DESCRIPTION OF THE DRAWINGS
The above mentioned and other features and objects of the present invention will become more apparent by reference to the following description taken in conjunction with the accompanying drawings, wherein like referenced numerals denote like elements, and in which:
FIG. 1 shows a sectional view of a prior art stainless steel "wood" club;
FIG. 2 shows a perspective view of a finished clubhead of this invention;
FIG. 3 shows a sectional view of a clubhead of this invention; and FIG. 4 shows an enlarged partial sectional view of the clubhead shown in FIG. 2.
DETAILED DESCRIPTION OF THE INVENTION
Referring more specifically to the figures, shown in FIG. 1 is a sectional view of a prior art "wood" clubhead illustrating the general construction of existing stainless steel "wood" clubheads, shown in FIG. 2 is a perspective view of a finished clubhead in accordance with the teachings of the present invention, shown in FIG. 3 is a sectional view of a basic structure of the clubhead of this invention, and shown in FIG. 4 is a partial sectional view of the clubhead structure of this invention illustrating the interconnection of the clubhead structure of this invention.
First referring to FIG. 1 showing a prior art clubhead structure, a clubhead 1 has a substantially straight neck 2 extending upwardly from its heel side 11. A shaft 6 is fitted into and coupled to the neck 2 by means of adhesive agents such as epoxy resin.
Since the neck portion has been considered to be one of the weakest areas of the clubheads, the lower end 3 of the neck 2 has to be expanded or flared. Accordingly, the flared lower end 3 of the neck 2 has a thicker wall than the upper end 4. It has been believed that the above configuration is essential to absorb the heavy stress created at the impact when striking a golf ball, thereby avoiding cracks at the neck area.
However, according to the prior art configuration, with the addition of a traditional persimmon wood neck structure, the weight at the heel side 11 tends to be heavier than the other side resulting in having the center of gravity (sweet-spot) shifted to the heel side. As a result, golfers have been experiencing difficulty in hitting a ball accurately and farther. In order to compensate for the shift of the sweet-spot, stainless steel "wood" heads have been kept compact as in FIG. 1. In Addition, the prior art structure in the neck area shows a straight neck extending from the flared lower end which looks substantially different from the traditional persimmon clubhead having a smooth tapered line in the neck area. This invention is to provide a practical solution to this problem.
Now referring to FIG. 2 showing a finished clubhead of this invention, the general appearance of the clubhead, is the same as the traditional persimmon wood club, which is substantially larger than the prior art stainless steel "wood" clubs.
The specific configuration of the clubhead of this invention is best shown in FIG. 3. The clubhead 1 has a top wall 8, a sole member 9, a toe side wall 10, and a heel side wall 11 to form a hollow body lA. The clubhead 1 also has a neck 2 which extends upwardly from a shoulder 13 located at the upper end of the heel side wall 11. The diameter of the neck 2 is substantially smaller than that of the shoulder 13. The neck 2 has a cylindrical shape with a relatively thin and even thickness wall from the lower end 3 to the upper end 4.
By thus constructing the clubhead, the weight balance of the clubhead may be kept as desired to have the sweet-spot 12 in the center of the hitting surface 7 (see FIG. 2). This allows golfers to hit a ball straighter and farther.
Experiments have been repeated in terms of the durability particularly at the neck area.
After a number of different types of tests, it has been observed that the thin neck and shoulder structure of this invention would not cause any more cracking or deterioration than the existing stainless steel "wood" clubs, provided that a proper material is used with the proper radiuses at the lower end 3 of the neck 2.
The thin neck and shoulder structure of this invention may properly be embodied as illustrated in FIG. 4.
The clubhead 1 is made of 17-4 Ph. stainless steel and has thickness between 0.03-0.05 inches. The neck 2 has a cylindrical wall slightly thinner than the remainder of the clubhead 1 whereby the weight balance between the heel side 11 and the toe side 10 may be very well kept to maintain the center of gravity (sweet-spot) in the desirable center 12 of the hitting surface 7 (see FIG. 2). The shaft 6 is accommodated in the neck 2 in such a manner that the tip portion 6A of the shaft 6 is in contact with a second shoulder 14 extending inwardly from the first shoulder 13.
In order to ensure a durable structure in the neck area, a radius 19 is provided between the lower end 3 and the shoulder 13 and another radius 20 is provided between the shoulder 13 and the end portion 15 of the clubhead 1. The radiuses 19 and 20 are given a curvature of 1/16"-1/2" and preferrably 1/8"-1/4" to most effectively strengthen the structure and prevent deterioration. In addition a plastic ferrule 16 is placed to cover the neck 2 and a part of the shaft 6. The ferrule 16 is designed to specifically match the size and the shape of the shoulder 13. It is preferable to have a reinforcing string 17 wound around the ferrule 16 such that the diameter of the end portion 15 of the clubhead 1 adjacent to the neck 2 is substantially the same as the diameter of the lower end portion 16A of the ferrule 16. The ferrule 16 has a tapered shape toward its upper end so that the neck area forms a smooth and natural configuration case as the traditional persimmon wood club. Urethane foam 18 or other light materials may be inserted in the head body lA to improve the sound effect.
As is clear from the above description, since the weight balance is well kept between the heel side 11 and the toe side 10, the center of gravity (sweet-spot) may be located in the desirable center 12 of the hitting surface 7. With this advantage and the common advantage for the stainless steel "wood" club such as wider sweet spot by added perimeter weight, the clubhead of this invention enjoys the benefit of more distance and straighter shots even with off center hits.
In all cases, it is understood that the above-described embodiments are merely illustrative of but a few of the many possible specific embodiments which represent the application of the principles of the present invention. Numerous and varied other arrangements can be readily devised by those skilled in the art without departing from the spirit and scope of the invention. | A golf club head for being fitted to a shaft wherein the golf club head is a stainless steel hollow body defining a hitting surface, a top wall, a sole member, a rear wall, a pair of side walls and a neck. The golf club head is further characterized in that the neck has a first shoulder at its lower end, the neck has a cylindrical portion extending upwardly from the first shoulder, the shaft is fitted into the cylindrical portion and a plastic ferrule is mounted around the cylindrical portion such that the plastic ferrule stands on the first shoulder. | 0 |
This is a continuation of application Ser. No. 07/681,295 filed Apr. 8, 1991 now abandoned.
BACKGROUND OF THE INVENTION
This invention relates to the art of powder metallurgy. This invention is the result of a contract with the Department of Energy (Contract No. W-7405-ENG-36).
Alloys of tungsten in uranium are conventionally produced by coreducing uranium tetrafluoride with tungsten oxide or tungsten fluoride. The maximum amount of tungsten which can be alloyed with uranium to obtain a coherent shape using this coreducing process is about 4 wt %. In U.S. Pat. No. 4,959,194, issued Sept. 25, 1990, entitled "High Strength Uranium-Tungsten Alloy Process" (Dunn et al.), a method of making alloys of tungsten and uranium is disclosed. These alloys may be described as dispersion-strengthened and precipitation-strengthened alloys where tungsten particles are uniformly dispersed throughout the alloy. The composition of these alloys ranges from about 4 wt % to about 35 wt % tungsten. In an article in the Journal of Metals (January 1950) entitled "The Alloy Systems Uranium-Tungsten, Uranium-Tantalum and Tungsten-Tantalum," Schramm, Gordon, and Kauffman reported on their work which resulted in construction of a phase diagram for the uranium tungsten system.
SUMMARY OF THE INVENTION
This invention is alloys of tungsten and uranium and a method for making the alloys. The amount of tungsten present in the alloys is from about 55 vol % to about 85 vol %. The mechanical properties of these alloys are a significant improvement over those of the alloys in the above mentioned patent. A porous preform is made by sintering consolidated tungsten powder. The preform is impregnated with molten uranium such that uranium fills the pores of the preform. Alternatively, the molten uranium will dissolve bonds between tungsten particles so that there is a continuous phase of uranium containing tungsten particles. To accomplish this, the preform is placed in a mold having dimensions larger than the preform and the molten uranium is poured into the mold. After cooling, the body is removed from the mold and the exterior skin of pure uranium is removed to obtain a body comprised of uranium and tungsten.
It is an object of this invention to provide high strength alloys containing uranium and to provide a process for making such alloys.
It is also an object of this invention to provide a high density alloy having an atomic cross-section close to that of uranium but having strength and stiffness greater than uranium.
In a broad embodiment, this invention is a method for making an alloy consisting of (1) a porous matrix formed of tungsten particles and uranium located in the pores of the matrix or (2) tungsten particles in a continuous uranium phase, where the amount of tungsten present in the alloy is from about 55 vol % to about 85 vol %, said method comprising consolidating tungsten powder by vibration or pressing; sintering said consolidated tungsten powder in a hydrogen atmosphere to form a coherent shape; placing said shape in a mold larger than said shape; subjecting said shape to a pressure of less than atmospheric pressure for a sufficient time period to effect degassing of said shape; heating said shape to a temperature of at least 950° C.; pouring molten uranium into said mold; allowing said mold and its contents to cool and removing the cast body from the mold; and removing uranium from the surfaces of said cast body to make the dimensions of said body approximately equal to the dimensions of said sintered shape.
DETAILED DESCRIPTION OF THE INVENTION
Tungsten-uranium alloys of this invention were prepared in the following manner. Commercially pure tungsten powder having nominal particle sizes of 4.5, 7.5, and 10 microns was obtained from General Electric. Powder of 19 microns was obtained from Kennametal of Latrobe, Pa. The four sizes of tungsten particles were not mixed; each alloy of the present invention was made using only one size of tungsten particles. The inventive alloys which were tested were made using 19 micron powder. It was determined that the 19 micron powder contained iron and nickel impurities. The uranium used to make the alloys was depleted uranium, which is substantially nonradioactive and is 99.98 wt % U 238 with the balance being U 235 . Tungsten powder was consolidated by subjecting it to vibration in a ceramic container or by isostatically pressing at room temperature. Pressing pressure was 50,000 psi (345 MPa); it is expected that pressures ranging from about 15,000 psi (103.5 MPa) to well above 50,000 psi may be used.
The consolidated powder was sintered to form a coherent shape, or porous preform, at about 1800° C. for about 2 hours. The sintered porous preforms had densities in the range of 50 to 80% of theoretical density. Sintering temperature may range from about 1250° to about 1850° C. and sintering may take from about one hour to about 4 hours. Sintering was done in a furnace in a hydrogen atmosphere in order to remove tungsten oxide which may have formed on the tungsten particles and to prevent further formation of tungsten oxide. The coherent shapes which were made were cylinders of 0.5 inches in diameter and 9 inches long. Sintering caused the tungsten particles to bond together to form a shape having open pores.
The preform was placed in a slight depression in the center of a cylindrical crucible having an inside diameter and a height greater than the outside dimensions of the preform. The crucible was graphite with a coating of stabilized zirconia to prevent reaction between the metals and the graphite. The porous preform was subjected to vacuum in order to remove gas in the pores of the preform in order to facilitate infiltration of the preform by molten uranium. The pressure was reduced to a value in a range of about 10 to 100 microns for at least 11/2 hours. The degassing period could be as long as 12 hours or as short as one-half hour. Uranium was melted in a similar crucible and brought to a temperature about 200° C. above its melting point. The melting point of uranium is about 1132° C. and that of tungsten is about 3410° C. An optical pyrometer was used to determine temperatures. The molten uranium was poured into the crucible containing the preform without moving the preform. The preform must be at a temperature of at least 950° C. degrees in order to prevent premature freezing of the uranium as it infiltrates the preform; in the experimentation, the preform was heated to 1000° C. The uranium must remain molten until it reaches the center of the preform. The temperature of the uranium added to the mold may range from about 150° to 300° C. above the melting point of uranium. The pressure of the atmosphere in which uranium is added to the mold may be increased to as high as 35 psi, in order to enhance infiltration into the preform.
After cooling, the cast body was removed from the mold and pure uranium was removed from it by machining to bring its dimensions to those of the preform, thus yielding a body consisting of tungsten and uranium.
Samples of the inventive alloys were subjected to mechanical testing in both tension and compression. Test results are presented in the Table. Data for pure uranium and pure tungsten are shown for purposes of comparison. Data for 80 vol % uranium/20 vol % tungsten which was made according to the process of the patent mentioned above is also presented; note the significant improvement in mechanical properties in the alloys of the present invention. Inventive alloys having 55, 70, and 72 vol % tungsten were tested. One of the samples was worked before testing and showed an increase in strength due to the working. The strengths of the 55 vol % tungsten alloy were surprisingly low; the reason for the low values is not known.
The size of the tungsten powder particles is determined by a Fisher sub-sieve sizer. It is expected that powder varying in size from the minimum readily obtainable (about 0.5 micron) to about 100 microns may be used in the present invention. Coherent shape refers to an object and is used to distinguish an object from a powder. Though only alloys having up to 77 vol % tungsten were prepared, I believe that this process may be used to make alloys having up to about 85 vol % tungsten.
The microstructures of the alloys can be varied by varying the sintering time and temperature to obtain two different forms. As the sintering time and temperature is increased, the size of the bonds between adjacent particles of tungsten, which are called the necks, increases. When molten uranium is added to the preform, it tends to preferentially dissolve the necks, since they are areas of high energy. If the necks are small, enough dissolution can take place such that the microstructure is particles of tungsten in uranium. With longer sintering time, the necks are not fully dissolved and the alloy is a tungsten matrix containing uranium. There are applications for both forms of microstructure: where uranium with a high loading of tungsten particles is desirable and also where a tungsten matrix containing uranium is wanted.
In both types of structures, when the relatively impure 19 micron nominal size tungsten powder was used in preparing the alloys, many fine tungsten particles were observed in the uranium phase. These particles were predominantly in the 3 to 6 micron size range with some in the 5 to 20 nm size range. When commercially pure 7.5 micron tungsten powder was used to prepare the alloys, fewer of the small tungsten particles were observed in the uranium phase.
TABLE______________________________________ Modulus of Yield Strength, Elasticity Density psi × 10.sup.3 psi × 10.sup.6Material Mg/m.sup.3 (MPa) (MPa × 10.sup.-3)______________________________________Tensile PropertiesW -- 78 (537) 58 (400).sup.2 W -- 95 (655) --U 19.0 26 (179.2) 21.1 (145.5).sup.1 U20% W19.06 101 (697) 27.4 (188.9)*U70% W19.21 142.5 (982) 41.8 (288.2)Compressive PropertiesU 19.0 47 (324) 24 (165).sup.1 U20% W19.06 90 (620) 28.3 (195)*U72% W19.22 190 (1309) 43.4 (299)*.sup.2 U72% W19.22 220 (1517) 43.4 (299)*U55% W19.16 83.2 (573) 28.0 (193)______________________________________ *Denotes the inventive alloys. .sup.1 Denotes alloys made per U.S. Pat. No. 4,959,194. .sup.2 This sample was worked before testing. | Alloys of tungsten and uranium and a method for making the alloys. The amount of tungsten present in the alloys is from about 55 vol % to about 85 vol %. A porous preform is made by sintering consolidated tungsten powder. The preform is impregnated with molten uranium such that (1) uranium fills the pores of the preform to form uranium in a tungsten matrix or (2) uranium dissolves portions of the preform to form a continuous uranium phase containing tungsten particles. | 2 |
CROSS-REFERENCES TO RELATED APPLICATIONS
This application claims the benefit of U.S. Provisional Application 61/246,929, filed Sep. 29, 2009.
FIELD OF THE INVENTION
In the construction of various projects utilizing concrete pipe, care must be taken to find a suitable method for filling voids of concrete pipe carrying various fluids and covering irregularities in pipe surfaces.
In constructing various concrete structures, numerous methods to prevent leakage and seal concrete pipes have been used, comprising butyls, plastics, asphalt and the like. Many non curing compounds utilizing polymers, pre-polymers or butyl materials when used alone lack the cohesive strength to provide for suitable compression at either an end flange or provide the necessary swell ability to fill voids. Cured compounds lack flexibility and become brittle from repeated thermal cycling. After being used for long periods, decreases in resiliency occur with a concomitant increase in creep reducing sealing capabilities. The use of polymer compounds in any underground concrete constructions has become problematic due to toxicity of component parts, levels of volatile organics and characteristic leaching which contaminates ground water or soil are common place.
Recently water-swelling compositions have been created by adding organic substances in non-cross-linked rubber compositions to improve the ability of these rubber compositions to fill voids or seal various pipes. Presently, proposed compositions have difficulties when compounded. The ratio of the water-swelling organic substance is low, so that sufficient leakage preventing abilities cannot be achieved, and conversely when the organic compounds are too high, the dispersion of the swell-able organic substance in the compounded matrix is insufficient and the strength of the composition is substantially reduced.
Additionally, swelling organic compounds are subjected to hydrolysis, oxidative deterioration, and further decomposition. Repeated swelling tends to weaken organic, non-organic and curing polymers as wet and dry cycles are repeated, with the residual low molecular weight components tending to cause negative environmental effects.
Various new materials have been used on preformed concrete joint members in the field of civil engineering construction. Such materials have been used at junctions of concrete pipes. Many are made of soft resilient asphalt, with some having semi-hard plastic cores enclosed by soft adhesive mainly consisting of polypropylene, or foamed plastics, or some are provided with adhesive layers disposed on all or a part of the outer surfaces, with resulting poor performance due to loss in compositional void filling once the liquid leaches out of the swelling polymer.
It is noted that joint portions of preformed concrete members are often made in socket-and-plug type or male-female type. Such joint portions cause leaks, because of insufficient dimensional accuracy in concrete surfaces, voids in the surfaces of concrete pipes and improper field work at the site, or uneven sinking of the land. Many if not all gaskets or seals or transition parts presently for concrete pipes and concrete structures are positioned only as the pipes are assembled or structures are built and require accurate positioning which is difficult or impossible. Where seals, gaskets or transition parts fail over time, the replacement of the joint seal is difficult at best.
The creation of an expanding void filler has been noted to provide several benefits, which include an ability to be dimensionally adjusted in the field. In one case, expanding the void filler in an elongated profile could be fitted to any size section of a pipe. In other cases, it has been noted that the expanding void filler provides for a controlled swell that is time dependent. That is, as the weeks go by, the material can continue to expand to fill voids in pipes or fit compressively against opposing faces at a joint. Additionally it has been noted in test and development that the expanding void filler can lose water without a concomitant loss in a newly expanded configuration. In another case, the expanding void filler when used as a gasket has tacky properties that allow it to stick to vertical side walls and maintain positioning between two opposing faces at a juncture.
SUMMARY OF THE INVENTION
In general, in a first aspect, the composition has hydrophilic reactants mixed with a hydrocarbon polymer and covalently bonded polymer and a rubber containing core component mixed with filler particles along with a plasticizer and a cross-linking agent. Various aspects may include one or more of the following features, at least one hydrophilic reactant, with the hydrophilic reactants having a range of OH numbers of at least 34 to 112 and a functionality of between from at least 2.0 to no more than 3.0 and a formula weight percent range of at least 5% to no more than 21%. Various other components may be a hydrocarbon polymer and a rubber containing core component.
In general, in a second aspect, the process of manufacturing an adhesive composition comprises the following steps: A mixture of a first, second and third hydrophilic reactants, is mixed with a hydrocarbon polymer and rubber containing core component and further blended with some additional filler particles. Control of the polymerization occurs by mixing the hydrophilic reactants with the cross-linking agents and particles. Further mixing of the polymerized reactants and particles with the rubber containing core component creates an adhesive composition. Such mixing of reactants and polymerization of reactants may be controlled with a rotational arm which is interconnected to a viscosity controller and meter. The mixing device is connected to the distal end of a mixing arm positioned inside of a container which is in turn thermally connected to a heating element. The heating element heats the adhesive composition in which case an interpenetrating rubber containing core component forms such that the rubber containing core component creates interstitial spaces. The interstitial space created contains particles as well as rubber.
Controlling the physical reaction step is linked to the control of the polymerization reaction. The physical reaction may be further controlled by controlling the speed of the rotational arm. The rotational arm and the temperature can be used to control the viscosity of the hydrophilic reactants of the adhesive composition. All the hydrophilic reactants are polyethers and mixed with particles which are entrained within the interstitial spaces created as the rubber and particles interpenetrate with the rubber containing core component. The interstitial spaces exist as a function of incomplete filling of the interstitial spaces by particles and rubber. Without particles, liquids may be entrained but the presence of particles allow for further entrainment of liquids and better development of cohesive strength. The hydrocarbon polymer may be one of many amorphous polymers.
In general, in a third aspect, the method of filling voids in surfaces having voids with a void filling material is accomplished using a time dependent hybrid material that corresponds to an liquid uptake of a plurality of different entrainments up to 150% of the weight of the hybrid material.
The method of filling voids in surfaces having voids with a void filler may include one or more of the following features: a mix of butyl rubber, and a rubber containing core component mixed with hydrophilic reactants and particles creating an interpenetrating structure that may attract and entrain liquids into the void filler. The void filler expands over time to fill surfaces, surface irregularities and voids, along the tubular surface of pipe sections or as between joint spaces.
In general in a fourth aspect, the method of mixing hydrophilic reactants is accomplished utilizing a system and an apparatus with a viscosity controller and an output viscosity meter measured by the heating of the mix in an intermediate mixing operation.
The method of mixing a hydrophilic reactant with a cross-linked rubber containing core component in an apparatus may include one or more of the following features. A mixture of a covalently bonded hydrophilic reactant with a cross-linked rubber is mixed with a rotational arm with such rotational arm electrically connected to the viscosity controller. The viscosity controller is further electrically attached to a viscosity meter. The heating element is thermally connected to a container for containing the compositions, mixtures, agents and reactants with a rotational sensor electrically connected to a viscosity meter to display the viscosity measurement.
In a fifth aspect, an article of manufacture may be any of a number of various forms including a gasket or an elongated profile as applied to pipe.
A gasket consisting of a compressively flexible part and an adhesive part both of which acting together provide an article that may be fitted between two opposing faces of a transition joint of any of a number of end fittings of pipe. In an elongated profile the gasket may be fitted to any dimension of pipe and applied in the field after the pipe is joined but before the pipe is completely compressed together.
DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS
As used herein, the hydroxyl number (OH number) is a measure of the concentration of the hydroxyl groups on a polyol. As used herein, the average functionality (i.e. the number of functional groups per polymeric chain) of the polyol can be estimated by:
f(HO)=(OH number×Mn)/56.100, where Mn is the number average molecular weight, which is the total weight of all the polymer molecules in a sample, divided by the total number of polymer molecules in a sample.
The adhesive composition of the expanding void filler of the claimed invention is both hydrophobic and hydrophilic. The adhesive composition is capable of adsorbing up to 150% by weight of entrained fluids without a concomitant loss in the newly formed volume or loss in the configuration obtained during the swell, once the liquid is removed. Hydrophilic polymers attract other polar bonded liquids.
The hydrophilic and hydrophobic polymers along with the rubber containing core component and the rubber of the expanding void filler imparts a controlled swell rate to the material. The controlled swell is equal to approximately 150% by weight of the expanding void filler present. Control of the swell is metered by the ratio of the hydrophilic polymer to the hydrophobic polymer.
The ratios of the ingredients are controlled so that the reinforcing phase, which is the phase that provides cohesive strength to the expanding void filler, is in excess of the absorbent phase, the phase that controls the absorption of polar liquids or other entrained fluids, so that sufficient cohesive strength is maintained, and liquid exudation is prevented in the finished product.
In one aspect of the expanding void filler, there exists a first liquid phase/hot melt hybrid adhesive technology that is based on a blend of functionally specific materials. The adhesive form is a liquid dispersion at room temperature, and is stable as a liquid when stored at temperatures of up to approximately 120° F. The first liquid phase of the adhesive fuses and melts when the dispersion is exposed to temperatures in excess of 250° F. However, with mixing, the dispersed ingredients form a second soluble, molten “hot-melt” solution, which can be dispensed like other hot melt adhesives. Once dispensed, the molten hot melt cools to form a third solid adhesive after processing.
The hot melt may be thermally stable for long periods of time at process temperatures, and like other thermoplastic adhesives, it can be re-melted, and reused after cooling. The achievement of fiber tear adhesion is strongly dependent on mixing (since there may be more than one polymer component and sometimes at least two polymer components), and on activation temperature. Inadequate mixing will result in cohesive failure of the adhesive. Similarly, the adhesive should be molten and mixed at temperatures in excess of 250° F. to activate the chemistry; otherwise, the adhesive may cohesively fail.
The adhesive compositions of the expanding void filler are based on blends of materials. It has been discovered that a liquid phase/hot melt hybrid of expanding void fillers contain a phase, which serves as the intermediate vehicle for dispersion of other components; a reinforcing phase, which gives the adhesive the requisite cohesive strength for the end use application; and an absorbent phase, which prevents exudation of the liquid phase during hot melt processing, during application, and during end-use. The adhesive compositions also preferably include an activator, which helps to prevent exudation in the finished product; a thermal stabilizer providing stability at process temperatures.
The expanding void filler is directed to a surface-tacky controlled, time dependent, swell capable, hot melt having an adhesive composition which contains at least a first hydrophilic reactant. The first hydrophilic reactant has an OH number of 56 but can range from between the low 30's to at least as high as 112. Additionally the first hydrophilic reactant exhibits a range of functionality from at least 2.0 rising to 3.0. The first hydrophilic reactant has a formula weight percent range of 10-20%.
The adhesive composition may also have a second hydrophilic reactant. The second hydrophilic reactant has an OH number of at least 34 ranging to as high as 56, with a functionality of at least 2.0 to a high of 3.0 with a formula weight percent range of 8-18%.
The adhesive composition may also have a third hydrophilic reactant having, an OH number of at least 56 ranging up to 112, and a functionality of at least 2.0; and a formula weight percent range of 5-12%.
The adhesive composition has a thermosetting polymeric isocyanate compound of the form of a NCO % (isocyanate %) of at least 30% with a functionality of 2.0-3.0.
The first hydrophilic reactant and the second hydrophilic reactant and the third hydrophilic reactant, are coupled with a hydrophobic polymer, rubber, and a rubber containing core component, a plurality of filler particles, a plasticizer, a cross-linking agent and a covalently bonded polymer. The covalently bonded polymer is amorphous polyolefin hydrocarbon and makes up 5-30% of the weight of the total mixture.
The rubber is any of a number of natural, butyl, or halogenated rubbers. In a range of 2% to 15% by weight of total weight of the mixture is composed of butyl rubber and 15% to 40% by weight of thermoplastic copolymer which may be at least two of the hydrophilic reactants, with a formula percent weight of 5% to 20% by weight of copolymers. Generally the polymers are mixed with a hydrocarbon polymer which exists in the range of 5% to 34% in the form of a polymeric isocyanate. The hydrophilic reactants are selected from the group consisting of water-soluble polymers, water-dispersible polymers, water-soluble co-polymers and mixtures thereof. About 15 to about 50% by weight of powder based absorbers or filler particles and about 0.2 to about 2.0% by weight stabilizers may also be added to the mixture. Both thermal and liquid entrainment are combined with the hydrophilic reactants, butyl rubber and the hydrocarbon polymer to form the interpenetrating rubber containing core component.
Some other ratios that are not exact, but having ratios that fall within the above ranges are also covered within the blending operation that allows for the mixing of various hydrophilic reactants with hydrocarbon reactants without the complete activation of the chemistry occurring. The mixing apparatus results in a more uniform blend, but current processing is unable to maintain the workability of the material through viscosity standard mixing is unable to create the smooth blending and activation required.
Another phase of the combination of the hydrophilic reactants with the hydrocarbon and the butyl is the blending in a separate apparatus which covers the mix with an inert gas that prevents the entrainment of moisture during the blending phase. Control of viscosity utilizes a rotational arm connected to a viscosity meter whose rate and stability of the viscosity is directly related to heating of the mixing container with a heating element positioned and controlled by the rotational controller and the viscosity controller. The output of the viscosity controller is a meter, which identifies a temperature dependency of the viscosity to the heating by the heating element and the rotational controller of the rotational arm. This apparatus can be used in the intermediate blending and mixing operation to stabilize the manufacture of the expanding void filler material disclosed and claimed herein. | An adhesive composition, a process of manufacture and a method of filling a surface having voids with a void filler are disclosed herein. Upon insertion between opposing surfaces or around an exposed surface, the void filler expands into and around the voids, filling surfaces having voids and covering irregularities of concrete structures. | 2 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a fishing rod rack assembly for supporting a plurality of fishing rods and more particularly to a fishing rod rack assembly which is removably engageable with the side walls of a bed of a pick up truck for the support of a plurality of fishing rods.
2. Description of the Prior Art
When a fisherman travels from his home to a location where he is going to conduct fishing, one of his concerns is for the protection of his fishing tackle, including the fishing rod and reel. If the fishing rod can be broken down into several components, then the transport of the rod is relatively easy. However, with some fishing rods such as surf casting rods, they do not break down and their length is sometimes in excess of 14 feet, and vertical clearance can become a problem with trees, power lines, toll booths, etc.
One solution for transporting rods of this type was to fashion a rod rack out of tubular material which would fasten to the front bumper and frame of the vehicle and support vertically oriented tubes into which the fishing rod could be slidably mounted, thereby transporting them in a vertical orientation at the front of the vehicle. This allows for the transport of a plurality of rods, but the rack itself requires some effort in order to install to the under chassis of the vehicle. Still further, in fabricating this rack, there is a certain limitation as to the number of vertical tubes that can be engaged on the rack for support of fishing rods.
Another solution to the problem has been roof racks for vehicles such as SUVs and station wagons in which the pole can be clamped in place or placed in tubes in a horizontal position on the roof of the vehicle. In such a situation, the placement of the roof rack requires some degree of effort and it is not easily removed and the positioning of fishing rods into the horizontal tubes or clamps is somewhat cumbersome.
Applicant has developed a fishing rod support rack which is cooperative with the side walls of a pick up truck and allows for quick installation and quick removal and can accommodate a greater number of fishing rods than currently available with fishing rod racks available in the market place, and can support those fishing rods at any selected angle from the horizontal to the vertical to enable the vertical clearance issue to be addressed.
OBJECTS OF THE INVENTION
An object of the present invention is to provide for a novel fishing rod rack for the support of fishing rods during transportation, which rack is easily installed and/or removed from the bed of a pick up truck.
Another object of the present invention is to provide for a novel fishing rod rack which can support a plurality of poles at any angle between the horizontal and the vertical.
A still further object of the present invention is to provide for a novel fishing rod rack for support of a plurality of fishing rods which allows fishing rods to be angularly stored on both sides of the support rod.
A still further object of the present invention is to provide for a novel fishing rod rack which allows the user to address vertical issues.
SUMMARY OF THE INVENTION
A fishing rod rack for the support of a plurality of fishing rods, the fishing rod rack spanning the width of the bed of a pick up truck, the fishing rod rack having a two piece bracket member at each end for engaging the inward lip of the respective side walls, there being a support rod extending between opposing bracket members, there being a plurality of support tubes rotatably secured to the support rod by a clasp member rotatable about the support rod and secured in angular position by a pair of set screws.
BRIEF DESCRIPTION OF THE DRAWINGS
These and other objects of the present invention will become apparent, particularly when taken in light of the following illustrations wherein:
FIG. 1 is a side view of the fishing rod rack assembly as viewed from the rear end of a pick up truck bed;
FIG. 2 is a side view of the fishing rod support tube assembly and mounting clasp; and
FIG. 3 is a top view of the fishing rod assembly secured between the side walls of a pick up truck.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 is a side view of the fishing rod rack assembly of the present invention as viewed from the open end of the bed of a pick up truck. The fishing rod rack assembly 10 is secured in an elevated orientation between the side walls 12 and 14 of the bed 16 of the pick up truck. The majority of pick up trucks come with three types of bed widths, standard, mid size, and compact. In all types, each side wall normally has an inwardly depending horizontal flange 18 and 20 defined by an upper surface 22 and a lower surface 24 . Applicant's assembly may be fabricated to fit each of the aforesaid bed types or any irregular bed width.
The first element of Applicant's fishing rod rack assembly is a tubular cross bar 26 preferably circular in cross section and rigid enough to support a plurality of fishing poles. Tubular cross bar 26 has an identical clamp mechanism 28 secured at its first end 30 and its second end 32 which clamp mechanism engages the horizontal flange 18 and 20 of side walls 12 and 14 . Clamp mechanism 28 comprises a first C-shaped member 34 having a first horizontal leg 36 and flange engaging surface 38 positioned on upper surface 22 of flange 18 or 20 . First C-shaped member 34 has a vertical leg 40 which is secured to the first horizontal leg 36 and also to the tubular cross bar 26 . Vertical leg 40 ends with a short horizontal leg 42 positioned below lower surface 24 of flange 18 or 20 . The second clamp member 44 is again C-shaped in cross section having a first vertical leg 46 in frictional engagement with the lower surface 24 of flanges 18 or 20 and terminating with a horizontal leg 48 extending beyond the end of flange 18 or 20 and a second vertical leg 50 extending below horizontal leg 48 and above horizontal leg to a point proximate flange 18 or 20 wherein second vertical leg 50 terminates with a horizontal lip 52 extending towards the opposing side wall. Formed in first horizontal leg 36 of first clamp member 34 is a throughbore 54 which is aligned with a threaded throughbore 56 formed on the lip member 52 of second vertical leg 50 of second clamp member 44 . A threaded fastener 58 extending through the aforesaid throughbores tightens first clamp member 36 and second clamp member 48 while simultaneously frictionally engaging the upper surface 22 and lower surface 24 of flanges 18 and 20 .
FIG. 2 is a side view of a tubular fishing rod holder 70 and the associated mounting clasp 72 for mounting same on tubular cross bar 26 . The tubular fishing rod holder 70 is generally circular in cross section and of a length and dimension sufficient to slidably receive the butt end of a fishing rod. Mounting clasp 72 secures the tubular rod holder 70 in selected angular rotation on tubular cross member 26 . The mounting clasp 72 comprises a first clasp member 74 having a first end 76 and a second end 78 , first clasp member 74 being generally flat on its upper surface 80 proximate the first end 76 and the second end 78 in order to accommodate a threaded bore proximate each end. First clasp member 74 is secured to tubular rod holder 70 by any suitable method, but preferably welded. An arcuate surface 82 is formed on first class member 74 between threaded bores, the arcuate surface 82 conforming to a portion of the circumference of tubular cross member 26 .
Second clasp member 84 is generally C-shaped, having a first end 86 and a second end 88 with lower surfaces 90 and 92 complimentary with planar surface 80 on first clasp member, the upper surface of second clasp member having a planar portion proximate its ends 86 and 88 to accommodate a throughbore alignable with said threaded bore in said first clasp member 74 , there being an arcuate surface 94 between said throughbores complimentary with a portion of the circumference of the tubular cross member 26 such that when first clasp member 74 and second clasp member 84 are joined and threaded fasteners 96 and 98 are introduced into the bores and secured, an aperture conforming to the outer dimension of the tubular cross member 26 is formed. This arrangement allows for a plurality of tubular rod holders 70 to be frictionally secured to tubular cross member 26 in a variety of angularly rotational selections.
FIG. 3 is a partial top view of the fishing pole holding assembly 10 secured to the side walls 12 and 14 of a pick up truck bed 16 . It should be noted that the user can position and secure the tubular rod holders 70 via the clasp member 72 to either a rearward angle configuration “A”, a forwardly angled configuration “B”, or a directly vertical configuration “C”. Still further, by being able to stagger the forward and rearward angularity of adjacent tubular rod holders 70 , the user can store many more poles on the fishing rod rack assembly. This is due to the fact that large fishing rods oftentimes have large reels which extend significantly to both sides of the rod. Therefore the tubular rod holder clasp 72 of an adjacent tubular rod holder 70 would have to be spaced some distance apart in order to accommodate an adjacent pole with a similarly large reel. However, by having the tubular rod holders 70 staggered forwardly and rearwardly, the spaced apart distance between adjacent tubular rod holders 70 is reduced to the diameter of the tubular rod holder 70 .
Applicant's fishing rod rack assembly solves the aforesaid problem of accommodating more rods, still further, allows the entire assembly to be removed and stored so that the pick up truck can be used for its other intended purposes, yet still be intalled quickly and easily with only a single wrench.
While the present invention has been described with respect to the exemplary embodiments thereof, it will be recognized by those of ordinary skill in the art that many modifications or changes can be achieved without departing from the spirit and scope of the invention. Therefore it is manifestly intended that the invention be limited only by the scope of the claims and the equivalence thereof. | A fishing rod rack for the support of a plurality of fishing rods, the fishing rod rack spanning the width of the bed of a pick up truck. The fishing rod rack has a two piece bracket member at each end for engaging the inward lip of the respective side walls, there being a support rod extending between opposing bracket members. A plurality of support tubes are rotatably secured to the support rod by a clasp member rotatable about the support rod and secured in angular position by a pair of set screws. | 0 |
TECHNICAL FIELD
[0001] This invention relates to vehicle cargo areas having a panel movable between a stowed position and an upright position to divide the cargo area and thereby prevent cargo shifting.
BACKGROUND OF THE INVENTION
[0002] Prior art pickup trucks include a cab for carrying a driver and one or more passengers, as well as a cargo box behind the cab for carrying cargo. The cargo box is typically defined by a cargo floor, two sidewalls, and the back of the cab. The cargo box includes an opening at the rearward end to facilitate the loading and unloading of cargo onto the cargo floor. A tailgate is pivotably mounted to the end of the cargo box to selectively close the rearward opening thereof. Cargo placed on the cargo floor adjacent the opening may shift forward during movement of the pickup truck, away from the opening.
[0003] Cargo boxes are typically open and exposed from the exterior. In order to secure personal items in the cargo box, a separate, lockable tool box is sometimes placed in the front portion of the cargo box. However, the tool box reduces the length of the cargo box available for cargo.
SUMMARY OF THE INVENTION
[0004] A pickup truck with a cargo box is provided. The cargo box includes a cargo floor and two sidewalls that cooperate to at least partially define a cargo area. The cargo box also includes at least one panel that is movably mounted with respect to the floor and selectively movable between a stowed position and an upright position. In the upright position, the panel extends higher into the cargo area thereby to separate a first portion of the cargo area and a second portion of the cargo area.
[0005] The panel, when upright, prevents the shifting of cargo during vehicle movement by creating a barrier to restrict cargo to one portion of the cargo area. Thus, if the panel is in close proximity to a rear opening of the cargo box, the panel prevents the shifting of cargo forward of the panel, thus keeping the cargo close to the opening for easy removal after transport.
[0006] In an exemplary embodiment, the panel defines a storage compartment with a closable door. The storage compartment provides secure storage for personal or other items, and, when the panel is in the stowed position, does not substantially affect the length of the cargo box available for other cargo.
[0007] The above features and advantages and other features and advantages of the present invention are readily apparent from the following detailed description of the best modes for carrying out the invention when taken in connection with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] FIG. 1 is a schematic, perspective view of a pickup truck including a cargo box bed liner having two selectively movable panels in respective stowed positions;
[0009] FIG. 2 is a schematic, perspective view of the bed liner of FIG. 1 with the two selectively movable panels in respective upright positions;
[0010] FIG. 3 is a schematic, rear view of the bed liner of FIGS. 1 and 2 ; and
[0011] FIG. 4 is a schematic, perspective view of the bed liner of FIGS. 1-3 with one of the movable panels in its respective stowed position and the other of the movable panels in its respective upright position.
DESCRIPTION OF THE PREFERRED EMBODIMENT
[0012] Referring to FIG. 1 , a pickup truck 10 is schematically depicted. The pickup truck 10 includes a cab 14 for enclosing a driver and one or more passengers. The pickup truck also includes a cargo box 16 that has two sidewalls 18 and a load floor 22 that cooperate with the rear panel of the cab 14 to define a cargo area 26 . The floor 22 and the sidewalls 18 cooperate to define an opening 27 at the rearward end of the cargo box 16 to facilitate the loading and unloading of cargo. A tailgate 29 is pivotable between an open position, as shown, and a closed position in which the tailgate 29 obstructs the opening 27 .
[0013] In the embodiment depicted, the pickup truck 10 includes a bed liner 30 inside the cargo area 26 . The bed liner 30 includes a member 32 that defines two sidewalls 34 and a floor 38 that cooperate to define cargo area 42 that is coextensive with cargo area 26 . As used in the claims, a “sidewall” or a “floor” of a cargo box may be part of the vehicle body, as sidewalls 18 and floor 22 , or they may be part of a bed liner, as sidewalls 34 and floor 38 . Member 32 also defines front wall 46 that defines the forward extent of cargo area 42 .
[0014] The member 32 may be of single-piece construction or multiple-piece construction within the scope of the claimed invention. Bed liner 30 is preferably configured not to interfere with the installation of after-market products such as caps, tonneau covers, etc. For example, sidewalls 34 are positioned under the upper rails of sidewalls 18 so that the bed liner is under or flush to the top of the cargo box 16 . Those skilled in the art will recognize a variety of materials that may be employed to form the member 32 within the scope of the claimed invention, such as polyethylene, fiber glass, etc.
[0015] A first panel 50 is pivotably connected at one end to the floor 38 via hinges (not shown). A second panel 54 is pivotably connected at one end to the floor 38 via hinges (not shown). The first panel 50 and the second panel 54 are shown in respective stowed positions in FIG. 1 .
[0016] When in their respective stowed positions, the panels 50 , 54 are arranged such that their smallest dimension (i.e., thickness) is vertically oriented to maximize vertical cargo space in the cargo area 42 . To further maximize the vertical cargo space in the cargo area 42 , the panels 50 , 54 rest on the floor 38 and are at least partially located in a respective concavity 58 , 62 formed in the floor 38 when in their respective stowed positions.
[0017] Each panel 50 , 54 is selectively pivotable approximately 90 degrees to a respective upright position, as shown in FIG. 2 . Referring to FIG. 2 , wherein like reference numbers refer to like components from FIG. 1 , panel 50 is oriented such that its smallest dimension is not vertically oriented, and, accordingly, the panel 50 extends higher into the cargo area 42 than when in the stowed position as shown in FIG. 1 . Similarly, panel 54 is oriented such that its smallest dimension is not vertically oriented, and, accordingly, the panel 54 extends higher into the cargo area 42 than when in the stowed position as shown in FIG. 1 . It may be desirable for the panels 50 , 54 to be made of a light-weight material, such as light-weight plastic, to facilitate the movement of the panels between the stowed and upright positions.
[0018] In the upright position, the panel 50 separates a first portion 66 of the cargo area 42 and a second portion 70 of the cargo area. Similarly, in the upright position, the panel 54 separates the second portion 70 of the cargo area 42 from a third portion 74 of the cargo area 42 . Each portion 66 , 70 , 74 forms a compartment. The panels 50 , 54 prevent load shifting by retaining cargo in a respective one of the compartments. Thus, for example, cargo placed in the first portion 66 of the cargo area will remain in the first portion 66 of the cargo area adjacent the opening 27 because of the first panel 50 .
[0019] Referring again to FIG. 1 , each sidewall 34 defines a respective forward protrusion 78 A and a respective rearward protrusion 78 B. Protrusions 78 A and 78 B extend inward into the cargo area 42 , and are sufficiently positioned to cause physical part interference with a respective one of the panels 50 , 54 in their upright positions. More specifically, and with reference to FIG. 2 , the rearward protrusions 78 B physically interfere with forward rotation of the first panel 50 in the upright position. Similarly, the forward protrusions 78 A physically interfere with the rearward rotation of the second panel 54 in the upright position.
[0020] Referring to FIG. 3 , wherein like reference numbers refer to like components from FIGS. 1 and 2 , each rearward protrusion 78 B has a latch member 82 thereon. The panel 50 , which is shown in its stowed position in FIG. 3 , has two latch members 86 mounted thereon for movement therewith. Latch members 86 are releasably engageable with latch members 82 . Each of latch members 86 is positioned on the panel 50 so as to align with, and engage, a respective one of the latch members 82 on a respective one of the rearward protrusions 78 B when the panel 50 is in the upright position.
[0021] Latch members 82 , 86 cooperate to form a latching system configured to releasably lock the panel 50 in the upright position. For example, latch members 82 may be latches such as those used with vehicle doors or tailgates, and latch members 86 may be strikers. Exemplary latches and strikers are described in U.S. Pat. No. 5,618,069, issued Apr. 8, 1997 to Konchan, et al., and U.S. Pat. No. 6,364,379, issued Apr. 2, 2002 to Roberts, et al., both of which are hereby incorporated by reference in their entireties. In the context of the claimed invention, a “latch system” may include any device or devices sufficiently configured to releasably retain a panel in its upright position.
[0022] When latch members 82 and latch members 86 are engaged with one another, they lock together, thereby locking the panel 50 with respect to the sidewalls 34 in the upright position. The latch members 82 , 86 are releasably engageable. A first latch release device 90 is mounted with respect to one of the sidewalls 34 , and a second latch release device 90 is mounted with respect to the other sidewall 34 . Exemplary latch release devices include push-buttons, pull handles, etc. Each latch release device 90 is operatively connected to both latches 82 on the rear protrusions 78 B, and each latch release device 90 is operative to selectively cause the disengagement of both of the latches 82 to release the panel 50 from its upright position. Thus, a vehicle user can disengage both latches 82 using a single latch release device 90 when moving the panel 50 from the upright position to the stowed position.
[0023] A connection system 94 operatively interconnects each release device 90 with both latches 82 . In an exemplary embodiment, the connection system 94 is mechanical, and employs cables or rods. In another exemplary embodiment, the connection system is electrical, and includes actuators (not shown) to cause the disengagement of the latches 82 . For clarity, the latch release devices are shown only in FIG. 3 . It should be noted that the latch system shown in FIG. 3 with respect to the first panel 50 and the rear protrusions 78 B is substantially similar to the latch system employed with the panel 54 and the forward protrusions 78 A.
[0024] Referring to FIG. 4 , wherein like reference numbers refer to like components from FIGS. 1-3 , each panel 50 , 54 defines storage compartments 100 therein. The floor 38 also defines a plurality of storage compartments 100 between the panels 50 , 54 . Each storage compartment 100 has a respective opening 102 . Each storage compartment 100 has a respective door 110 that is pivotably connected with respect to a panel 50 , 54 or the floor 38 and that is movable between an open position and a closed position. In the closed position, each door 110 closes a respective opening 102 to secure a respective storage compartment 100 . All doors 110 are shown in respective closed positions in FIGS. 1 and 2 . The doors 110 that are pivotably connected to the panel 50 are depicted in their respective open positions in FIG. 4 , as are two of the doors 110 pivotably connected to the floor 38 .
[0025] While the best mode for carrying out the invention have been described in detail, those familiar with the art to which this invention relates will recognize various alternative designs and embodiments for practicing the invention within the scope of the appended claims. | A pickup truck cargo box includes a cargo floor and a panel being movably mounted with respect to the cargo floor. The panel is movable between a stowed position and an upright position, in which the panel extends higher into a cargo area to form a compartment within the cargo area. The panel prevents the shifting of cargo during transport when upright, and is stowable to maximize the uninterrupted cargo area available. | 1 |
BACKGROUND OF THE INVENTION
The present invention relates generally to passive restraint systems and, more particularly, to a gas generator which uses electrothermal energy to produce gas of sufficient quantity to inflate an air cushion of an occupant restraint system of the "air bag" type.
Occupant restraint systems of the "air bag" type have been developed in response to the need to better protect occupants of automobiles from serious injuries common in vehicular accidents. To be effective as a passive restraint , the air cushion of the system must be fully inflated within approximately 50 msec., or less, of crash impact which time depends upon, among other things, the time required to sense the magnitude and position of the crash.
Throughout the evolution of "air bag" type occupant restraint systems there has been the persistent problem of a lack of suitable inflation gas generating means. This is because the gas generator must be capable of generating enough gas, up to 500 liters, to completely inflate the air bag within the 20-50 msec. of available time. The system must produce generally non-toxic and non-combustible gas to inflate the air cushion because the air cushion ultimately vents into the passenger compartment on deflation and because of the possibility of a cushion failure in an actual crash situation or during an inadvertent inflation in a non-crash condition. Also, the gas generator must be capable of lying dormant under a wide range of environmental conditions for several years without affecting the operability of the system in the event of a crash.
The goal of rapid generation of non-toxic inflation gas having long-term operability has been met with varying levels of success.
The first systems attempting to meet the requirements of a truly functional "air bag" type passenger restraint systems used high pressure stored gas to inflate the air cushion. Upon sensing a deceleration greater than a predetermined threshold level, gas from the storage container would be released, inflating the air cushion. Although these devices adequately inflated the air cushion, they had numerous disadvantages including weight, size, cost, and reliability. An example of such a device is provided by U.S. Pat. No. 3,837,671, which is incorporated herein by reference.
Pyrotechnic gas generators have also been used, wherein a propellant, such as sodium azide, is burned to generate an adequate amount of gas upon vehicle impact. An example of gas generators which burn sodium azide is provided by U.S. Pat. No. 4,929,290, which is incorporated herein by reference. The sodium azide inflator has many drawbacks. First, the basic manufacture of the propellant is hazardous, there being a significant risk of accidental fire and explosion at least until the propellant is pelletized. Second, sodium azide, when ignited, can produce harmful by-products and partially combusted materials that can burn through the cushion material of the air cushion. To prevent the partially combusted materials from injuring the occupants, a gas filter is provided and the inside of the air cushion is specially coated to resist "burn through." Further shortcomings of sodium azide inflators include undesirable size, weight, cost and the fact that it is neither readily testable nor reusable.
A third gas generating device that has been proposed is a combination of the previously mentioned stored gas and combustible propellant devices. In this scheme, the propellant is ignited and the gas generated thereby is supplemented by the stored, high pressure gas. An example of such a device is provided by U.S. Pat. No. 3,966,226, which is incorporated herein by reference.
None of the aforementioned devices is particularly attractive due to the shortcomings mentioned. These limitations make the commercial production and implementation of "air bag" type occupant restraint systems difficult. As consumer demand and governmental safety requirements continue to increase, there exists a need for a gas generating device which overcomes the limitations of those noted above.
SUMMARY OF THE INVENTION
In accordance with the present invention, an "air bag" type occupant restraint system is provided that includes a single sensor or a series of sensors mounted at various points on the automobile, the mounting points being such that a deceleration of the vehicle due to a collision may be readily sensed as to position and magnitude.
An electrothermal device is electrically connected to an electronic control unit (hereafter ECU) which receives information from the various sensors so that deceleration of a predetermined magnitude and position will be immediately communicated to the ECU to initiate the gas generation process.
The electrothermal device includes an inner hollow space forming a chamber or cavity having electrodes mounted therein. Upon command to initiate the inflation process the ECU sends a high voltage pulse to the electrodes which creates an arc between the electrodes and generates a plasma bubble or jet. The high voltage, low current pulse which initiates the gas generates process is provided by an energy storage device such as a capacitor, a group of capacitors or a battery means. The energy storage device may be integral with the ECU or separate from it.
The ECU continues to provide energy to the electrothermal device and the plasma jet is communicated via communication channels to a second chamber containing reactive material. The high temperature of the plasma jet causes the reactive material to be converted into pressurized gas which in turn travels into and inflates the air cushion. The chamber containing reactive material is in communication with the interior of the air cushion of the system via communication passages which allow the gas to flow from the chamber into the air cushion and thereby inflate the air cushion. The communication passages are provided with filters to remove particulate matter from the gas prior to inflation of the cushion. The air cushion used can be either aspirated or non-aspirated. An example of aspirated air cushions is provided by U.S. Pat. No. 3,910,595.
The reactive material is converted to pressurized gas in a non-combustion chemical reaction, unlike the prior art pyrotechnic devices. The reactive material of the present invention is stable over a wide range of environmental conditions, reacting only at high temperatures such as those crated by the plasma. Hence, manufacturing and disposal hazards occurring in devices currently in use are alleviated.
The ECU of the present invention is capable of controlling the amount of time the power supply provides energy to the electrothermal device and, correspondingly, the amount of reactive material that is converted into gas.
The time between impact and full inflation of the air bag is well within the time required of a device of this sort, even given the time needed to sense deceleration and initiate the gas generation process. Additionally, the gas produced by the gas generator is nontoxic, making passenger exposure thereto of no health concern.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic drawing of the major components of the present invention.
FIG. 2 is a detailed drawing of the electrothermal device and electrothermal gas generator of the present invention.
FIG. 3 is a detailed drawing of a second embodiment of the electrothermal gas generating device of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Reference is now made to FIG. 1, wherein the inflatable occupant restraint system (11) is illustrated as including a single or a group of deceleration sensors (10), an electrothermal device (14), an electrothermal gas generator (16), an electronic control unit or ECU (12) with an associated electrical power supply (13), an inflatable air cushion (18) and a cover (20) which separates the air cushion from the passenger compartment and opens under inflation conditions. The power supply (13) can be in the form of capacitors, batteries or a combination thereof suitable to provide a high voltage, low current pulse to the electrothermal device, as is well known in the art of electrothermal expansion as exemplified by U.S. Pat. Nos. 4,957,035 and 4,715,261, which are incorporated herein by reference. The power supply (13) can also be integral with the ECU (12).
In response to a signal from the sensors (10), indicating that a deceleration above a predetermined maximum level and impact direction has occurred, the ECU (12) verifies the crash event for position and level and, if verified as a threshold exceeding deceleration, the ECU electrically connects the power supply (13) to the electrothermal device (14).
The threshold level of deceleration necessary to cause the sensors (10) to activate the system (11) depends upon the characteristics of the automobile in which the system is utilized. Therefore, the sensitivity of the system to activation by the sensors (10), including the sensors in the ECU (12), can be adjusted to meet the specific automobile occupant restraint system requirements, as is well known in the art.
Referring to FIG. 2, the electrothermal device (14) of the present invention includes a housing (21) designed to sealably fit within an opening (22) of a housing (24) of the electrothermal gas generator (16). In the illustrated embodiment, sealing is accomplished by the use of threads (23) of the electrothermal device housing (21) interacting with mating threads (25) of the opening (22) in the electrothermal gas generator housing (24), however, it is realized that several other equivalent methods of sealing could be utilized.
In the illustrated embodiment, the shape of the electrothermal device housing (21) and electrothermal gas generator housing (24) are provided to illustrate the relationship of the structural features of the present invention. Naturally, the shape of the electrothermal gas generator (16) and electrothermal device (14) is dependent upon the area provided or available in the host automobile. Typically, for a driver-side unit, the electrothermal gas generator (16) and electrothermal device (14) are generally annular in shape, having a circular cross section whereas a passenger-side unit is usually longer and more cylindrical in shape, while retaining the generally circular cross section.
A series of communication apertures (26) in the electrothermal device housing (21) are positioned to match corresponding apertures (27) in the housing (24) of the electrothermal gas generator (16) to allow communication there between. The aligned fluid communication apertures (26,27) are located to facilitate immediate and direct communication between the electrothermal device (14) and the electrothermal gas generator (16).
The electrothermal device (14) is generally hollow and provides electrodes (28) connected by a fusible link (30). The fusible link (30) is chosen from material having known operating characteristics so that performance is reliable and testing is possible. There are numerous types of fuse-links known in the art, the type selected depending upon the features desired. However, in the preferred embodiment the link is a thin aluminum wire.
The continued viability of the fusible link (30) can be tested by pulsing energy through it that is lower than the level necessary to vaporize it and detecting current flow therethrough. In this way, an automatic partial system test is possible, for example, each time the automobile is started or continuously during operation as part of the automobile diagnostics. The ECU (12) of the present invention also provides a full system diagnostic function to monitor the status of all elements of the system.
Reactive material (34) in a solid or liquid state is contained within the electrothermal gas generator housing (24) which surrounds the electrothermal device (14). The open ends (32) of the electrothermal gas generator housing are provided with conventional particulate filters (36), although these are not required with some reactive materials.
The reactive material (34) of the preferred embodiment can be a combination of aluminum metal powder and water gel. This combination is extremely stable over a wide range of environmental conditions, reacting only at high temperature and pressure, such as that created by the electrothermal device (14). Naturally, other reactive materials could be substituted for the one presently disclosed without going beyond the scope of the inventive concepts as embodied in the appended claims.
The operation of the electrothermal device and generator of the present invention will be described hereafter with reference to the aforementioned drawings.
Once deceleration above a predetermined threshold level is detected by sensors (10), and then transmitted to and verified by the ECU (12), the power supply (13) is connected across the electrodes (28) of the electrothermal device (14) causing the fusible link (30) to melt or vaporize, sustaining an arc between the electrodes (28), creating ionized gas or plasma as is known in the art of plasma generation. The arc between the electrodes (28) can also be formed without using the fusible wire (30) by adjusting the distance between the electrodes (28) and the voltage supplied by the power supply (13) such that voltage across the electrodes causes an arc to be formed, similar to the arc formed by vaporization of the fusible wire.
The high temperature plasma jet exits the electrothermal device (14) via the communication apertures (26,27) and enters the electrothermal gas generator (16). The plasma jet converts the reactive material (34) into gas which then flows through the communication passages (32) of the electrothermal gas generator housing (24), through the filters (36) and into the air cushion (18). The filters (36) remove any particulate matter from the gas before it enters the air cushion (18). As the air cushion pressurizes, it breaks through the cover (20) and enters the passenger compartment to restrain and protect the occupants therein. The gas cools as it flows into the air cushion (18), thereby lessening the risk of burns to the occupant.
The length of time the power supply (13) is connected to the electrothermal device (14) is controlled by the ECU (12). This control function is important in that it indirectly determines the pressure to time relationship of the generated gas which must be optimized for the specific vehicle and the expected occupant kinematics. The ECU can stop inflation of the air cushion (18) by disconnecting the power supply (13) from the electrothermal device (14). By controlling the length of time the plasma forming voltage is available, it is possible to have controlled generation of gas. Hence, the pressure and the amount or volume of gas generated and flowing into the air cushion is controlled by adjusting the time the power supply is connected to the electrothermal device. In this way, the pressure and the amount of gas generated can be customized to the air cushion requirements of the particular host automobile under crash conditions.
It is important to note that the gas created by this process cools quickly as it fills the air cushion. The lower temperature eliminates the risk of burns to the occupant as the gas normally vents to the passenger compartment or in case of a cushion failure.
In the preferred embodiment, the system can be recharged after use, thereby making it reusable. This is accomplished by removing the electrothermal device (14) and replacing the fusible link (30) between the electrodes (28), replenishing the reactive material (34 within the electrothermal gas generator (16) and replacing the filters (36) if contaminated, with new ones.
In a second embodiment, as shown in FIG. 3, the inflatable occupant restraint system (11) is provided with several independent electrothermal gas generators (16) and electrothermal devices (14). Although all of the electrothermal gas generators (16) are in communication with the air cushion (18) via their respective filters (36), only one electrothermal device (14) is activatable by the ECU (12). After the reactive material (34) in the first electrothermal gas generator (16) is used to generate gas, the next electrothermal device can be electrically connected to the ECU to ready the system for use. In this manner, the system (11) is capable of use in several crashes without the need for replacement or recharge.
In a similar fashion, the electrothermal devices (14) are capable of being simultaneously activated and controlled by the ECU (12), activation of any device depending upon the intensity and direction of the sensed deceleration. The logic of the ECU would determine which, if any, of the chambers were necessary to inflate the air cushion. In this way, the cushion would be capable of controlled inflation rather than a mandatory complete inflation. The device would also be capable of multiple inflations in the event of a secondary impact, as is somewhat common in vehicular accidents.
While there has been described and illustrated one specific embodiment of the invention, it is clear that the description of the present invention is by way of example and variation therein can be made without changing the inventive concept as embodied in the claims attached hereto. For example, there are numerous ways of generating an arc between the electrodes of the present invention, such as directly between the electrodes without the use of a fuse link the described method being the method preferred by applicant.
Also, in the preferred embodiment, as disclosed above, it is possible to place the entire sensor function with the ECU. It is also possible to integrate the ECU, power supply, sensors, electrothermal device and gas generator into a single unit. Therefore, the entire inflatable occupant restraint system could be manufactured and installed as a unit, making installation and replacement a simple matter. | An electrothermal gas generating device for inflating the air cushion of an occupant restraint system of the "air bag" type. Upon sensing a deceleration above a predetermined threshold level a discharge voltage is applied between electrodes within the electrothermal device which sustains a current arc therebetween, creating a plasma jet which flows into a chamber containing a solid or liquid reactive material. The reactive material is converted into gas by the high temperature, high pressure plasma jet. The gas created then flows into and inflates the air cushion. | 1 |
TECHNICAL FIELD
[0001] The invention relates to a water separator element for a fuel filter of a motor vehicle.
PRIOR ART
[0002] A water separator element for filtering fuel of a motor vehicle is known from DE 2011 078 362 A1. The known water separator element is embodied in two stages for separating water. It has a particle filter medium and a final separator screen for separating water. The separated water collects in a water collection chamber. A water level sensor whose electrodes are conducted in a supporting rod of the fuel filter detects when the level of the accumulated water in the water collection chamber is too high.
[0003] Moreover, known from DE 10 2011 081 141 A1 is providing a dewatering device on a filter housing in order to be able to drain separated water out of the filter housing. The dewatering device is coupled to the filter housing via a snap-on connector.
[0004] WO 2010/049208 A1 discloses a filter device having a water sensor that in the structural unit is embodied with a heating circuit of the filter device. The water sensor has sensor pins that may be coupled to a socket connector via electrical contacts.
[0005] Known from US 2010/0276352 A1 is providing a filter with electrodes for detecting the water level. The electrodes are elastically prestressed and touch one another when the water separator element is in the uninstalled condition. Installing the water separator element causes the electrodes to separate from one another so that they are electrically insulated from one another and only conduct electrical current if the water level is too high. This means that the electrodes are used both for detecting the water level and for ensuring that the water separator element is correctly installed.
[0006] The reliability of water detection in the water collection chamber drops, however, due to wear and impurities in the fuel filter.
SUMMARY
[0007] The underlying object of the invention is therefore to make possible long-lasting reliable water detection in a fuel filter.
[0008] The object according to the invention is thus solved using a water separator element for a fuel filter of a motor vehicle, the water separator element having two water level electrodes for detecting accumulated water in a water collection chamber of the fuel filter and the water level electrodes being electrically contactable by means of two contact electrodes, wherein the contact electrodes may be connected in an electrically conductive manner to the water level electrodes.
[0009] When the water separator element is exchanged, the water level electrodes are replaced due to the arrangement of the water level electrodes on the water separator element. Water detection may therefore be long-lastingly reliable.
[0010] The water separator element advantageously has a particle filter medium that is supported on a center tube. In this case the water separator element is in the form of a filter element.
[0011] The water separator element may have a sedimentation opening for water separation. The sedimentation opening is preferably embodied on an end disk of the water separator element. The sedimentation opening is particularly preferably embodied in the form of a sedimentation gap.
[0012] Water separation occurs at particularly high efficiency when the water separator element has a coalescer medium, in particular in the form of a non-woven fabric.
[0013] For separating water, the water separator element may furthermore have a final separator screen, wherein the final separator screen is arranged or embodied in a screen support, the screen support being arranged or embodied radially to the water separator element. The water separating rate is increased significantly using the final separator screen.
[0014] A first contact electrode may be embodied radial to the water separator element longitudinal axis.
[0015] Both contact electrodes are preferably embodied annular radial to the water separator element longitudinal axis. Using the annularly embodied contact electrodes, the screen support may be mounted, rotated about the water separator element in practically any manner, the electrical connection to the water level electrodes being provided in every case.
[0016] The water level electrodes may be embodied in one piece/integrally with the contact electrodes. In this way it is possible to reliably ensure the electrical connection between the water level electrodes and the contact electrodes.
[0017] The contact electrodes may be arranged or embodied, at least in part, on an end plate of the water separator element. Because of this, the contact electrodes may be easily contacted by tapping electrodes arranged on the filter housing.
[0018] At least one connecting line between a water level electrode and a contact electrode may run in the screen support. Alternatively or in addition thereto, a connecting line may run in a center tube.
[0019] A first water level electrode is preferably connected via an electrical connecting line to a first contact electrode that is outwardly disposed relative to the water separator element longitudinal axis, and a second water level electrode is connected to a second contact electrode that is inwardly disposed with respect to the water separator element longitudinal axis, at least part of the connecting line running embedded in the end plate between the second contact electrode and an under side of the end plate. Because of this the water level electrodes may be spaced essentially the same distance from the water separator element longitudinal axis without this resulting in a short circuit between the water level electrodes. Segments of the end plate act as insulators between the second contact electrode and the connecting line.
[0020] The screen support and/or the center tube may be connected via a snap-on connector to the end plate of the water separator element, the water level electrodes each being electrically connected to the contact electrodes via an interruptible resilient contact when the screen support is locked to the end plate. The screen support or the center tube is particularly easy to assemble because of the snap-on connector.
[0021] In another preferred embodiment of the invention, the contact electrodes are arranged or embodied in an interior chamber of the screen support, the contact electrodes each being contactable using a tapping electrode embodied resiliently, at least in part, and the tapping electrodes being arranged or embodied, at least in segments, oriented radially outward on a center tube element of the filter. A particularly easily assembled water separator element is attained using such an arrangement, the electrical connection of the water level electrodes arranged or embodied “below” on the screen support being guided “upward” via the tapping electrodes and beyond via the center tube element.
[0022] It is particularly preferred that the screen support be embodied closed at its under side facing the water level electrodes in the region of the center tube element. The lower part of the inner chamber of the screen support, i.e. the part of the inner chamber of the screen support that can be directed towards the water collection chamber, is preferably embodied closed. Because of this, it is possible to forego a seal between center tube element and screen support, and it is possible especially to forego assembling a sealing ring between center tube element and screen support.
[0023] It is possible to attain a particularly compact and easily assembled structure of the water separator element when the particle filter medium, the coalescer medium, the sedimentation opening, and the final separator screen are arranged successively radial to the water separator element longitudinal axis.
[0024] In another embodiment of the invention, the water separator element may have an electrically conductive shorting bridge for electrically bridging at least two filter housing electrodes arranged or embodied on the interior of the filter housing. Due to the electrically conductive shorting bridge, it may be assured that the water separator element is correctly inserted into the filter housing. Moreover, due to such a shorting bridge it may be assured that only original water separator elements are used in the filter housing, so that damage to the engine due to deficient imitation water separator elements is prevented.
[0025] The invention furthermore relates to a filter having a previously described water separator element and a filter housing that has a water collection chamber, the water level electrodes projecting, at least in part, into the water collection chamber when the water separator element is inserted into the filter housing.
BRIEF DESCRIPTION OF THE DRAWINGS
[0026] Additional features and advantages of the invention result from the following detailed description of a number of exemplary embodiments of the invention, using the figures in the drawings, which illustrate details essential to the invention, and from the claims.
[0027] The features depicted in the drawings are illustrated such that the special qualities of the invention may be rendered visibly clear. Each of the various features may be realized individually by itself or with other features in any combinations for variants of the invention.
[0028] FIG. 1 a is a sectional perspective elevation of a first water separator element in a highly schematic first filter housing;
[0029] FIG. 1 b is a partial view of the left side of the first water separator element from FIG. 1 a;
[0030] FIG. 1 c is a partial view of the right side of the first water separator element from FIG. 1 a;
[0031] FIG. 2 is a sectional view of a second water separator element;
[0032] FIG. 3 a depicts screen support and center tube element of a third water separator element;
[0033] FIG. 3 b depicts the center tube element from FIG. 3 a , without screen support;
[0034] FIG. 3 c depicts a partial sectional view of the third water separator element from FIG. 3 a;
[0035] FIG. 4 a is a perspective elevation of a fourth water separator element;
[0036] FIG. 4 b is a top view of a second filter housing for receiving the fourth water separator element from FIG. 4 a;
[0037] FIG. 4 c is a partial sectional view of the second filter housing according to FIG. 4 b with fourth water separator element according to FIG. 4 a inserted therein;
[0038] FIG. 5 a is a perspective elevation of a fifth water separator element;
[0039] FIG. 5 b is a partial sectional view of the fifth water separator element according to FIG. 5 a in a third filter housing;
[0040] FIG. 6 a is a perspective elevation of a sixth water separator element;
[0041] FIG. 6 b is a perspective elevation of a fourth filter housing for receiving the sixth water separator element from FIG. 6 a;
[0042] FIG. 6 c is a partial sectional view of the fourth filter housing according to FIG. 6 b with sixth water separator element according to FIG. 6 a inserted therein;
[0043] FIG. 7 a is a perspective elevation of a seventh water separator element;
[0044] FIG. 7 b is a perspective elevation of a fifth filter housing for receiving the seventh water separator element from FIG. 7 a;
[0045] FIG. 7 c is a partial sectional view of the fifth filter housing according to FIG. 7 b with seventh water separator element according to FIG. 7 a inserted therein;
[0046] FIG. 8 is a top view of an eighth water separator element; and,
[0047] FIG. 9 is a top view of a ninth water separator element.
DETAILED DESCRIPTION
[0048] FIG. 1 a depicts a first filter 10 in the form of a fuel filter for a motor vehicle (not shown) having a first filter housing 12 that is merely indicated schematically with broken lines. A first water separator element 14 is inserted into the first filter housing 12 . The first water separator element 14 has a particle filter medium 16 , a coalescer medium 18 , a sedimentation opening 20 , and a final separator screen 22 . For reasons of clarity, in FIG. 1 a only the end faces of the final separator screen 22 are depicted. A dot-dash arrow 28 indicates the path of the fuel through the particle filter medium 16 , the coalescer medium 18 , the sedimentation opening 20 , and the final separator screen 22 . It may be seen that the particle filter medium 16 , the coalescer medium 18 , the sedimentation opening 20 , and the final separator screen 22 are arranged radial to a water separator element longitudinal axis 30 . The first water separator element 14 is embodied essentially axially symmetrical to the water separator element longitudinal axis 30 .
[0049] Using the coalescer medium 18 , the sedimentation opening 20 , and the final separator screen 22 , the fuel may be effectively freed of water in order to prevent engine damage. The separated water collects in a water collection chamber 32 of the first filter housing 12 . If the water level in the water collection chamber 32 is too high, this is detected by the water level electrodes 34 , 36 . The water level electrodes 34 , 36 and the final separator screen are arranged on a screen support 38 . The water level electrodes 34 , 36 may be electrically contacted via contact electrodes 40 , 42 . Particularly simple contacting of the contact electrodes 40 , 42 and simple assembly of the first water separator element 14 is attained using an annular embodiment of the contact electrodes 40 , 42 : Using the annular embodiment of the contact electrodes 40 , 42 , the first water separator element 14 , rotated as desired about the water separator element longitudinal axis 30 , may be inserted into the first filter housing 12 , and nevertheless always be correctly contacted. Water detection can always occur reliably because when the water separator element 14 is changed, the water level electrodes 34 , 36 are also exchanged and thus replaced.
[0050] FIG. 1 b is a partial view of the first water separator element 14 . It may be seen from FIG. 1 b that the radially exterior, first contact electrode 40 is electrically connected to the first water level electrode 34 via an electrical connecting line 44 . The connecting line 44 runs embedded in an end plate 46 of the first water separator element 14 . The first contact electrode 40 and the electrical connecting line 44 are embodied integrally. Moreover, the connecting line 44 and the first water level electrode 34 may be embodied integrally. In the present case, the connecting line 44 and the first water level electrode 34 are electrically connected via a first resilient contact 48 . The screen support 38 may be connected to the end plate 46 of the first water separator element 14 via a snap-on connector 50 . This permits particularly simple assembly of the screen support 38 . When assembling the screen support 38 , an electrically conductive connection between the first water level electrode 34 and the first contact electrode 40 is simultaneously created by the first resilient contact 48 .
[0051] FIG. 1 c is another partial view of the first water separator element 14 . It may be seen from FIG. 1 c that the radially inner, second contact electrode 42 is electrically connected to the second water level electrode 36 via a second resilient contact 52 . When assembling the screen support 38 using the snap-on connector 50 , an electrically conductive connection between the second water level electrode 36 and the second contact electrode 42 is simultaneously created by the second resilient contact 52 .
[0052] FIG. 2 depicts a second water separator element 54 . The second water separator element 54 is identical to the first water separator element 14 . However, water level electrodes 56 , 58 are not positioned mutually diametrically like the water level electrodes 34 , 36 (see FIG. 1 a ), but instead are spaced apart, at a right angle, about a water separator element longitudinal axis 60 . Moreover, a screen support 62 is embodied integrally with an end plate 64 , the first water level electrode 56 is embodied integrally with a first contact electrode 66 , and the second water level electrode 58 is embodied integrally with a second contact electrode 68 .
[0053] FIG. 3 a depicts a center tube element 70 of a fuel filter and a screen support 72 of a third water separator element. The center tube element 70 is not a part of a water separator element. The screen support 72 has water level electrodes 74 , 76 . The water level electrodes 74 , 76 are each electrically connected to tapping electrodes 78 , 80 . On its outer circumference, the screen support 72 furthermore has a final separator screen, however for reasons of clarity it is not shown.
[0054] FIG. 3 b depicts the center tube element. 70 . It may be seen from FIG. 3 b that segments of the tapping electrodes 78 , 80 are embodied resiliently. The tapping electrodes 78 , 80 produce an electrical connection to the water level electrodes 74 , 76 (see FIG. 3 a ).
[0055] In a partial sectional view of the center tube element 70 and screen support 72 according to FIG. 3 a , FIG. 3 c illustrates how this electrical connection is produced. The water level electrodes 74 , 76 (of which only the first water level electrode 74 is depicted in FIG. 3 c ) are each electrically connected to annular contact electrodes 82 , 84 . The water level electrodes 74 , 76 (see FIG. 3 a ) are embodied integrally with the contact electrodes 82 , 84 , respectively. The contact electrodes 82 , 84 are contacted by the tapping electrodes 78 , 80 , respectively, at least segments of which are resilient, and are each arranged, on the center tube element 70 , with a segment oriented radially outward, and their resiliently embodied segments press against the contact electrodes 82 , 84 .
[0056] The screen support 72 is embodied closed on the under side 90 facing towards the water level electrodes 74 , 76 (see FIG. 3 a ) in the region of the center tube element 70 . Because of this it is possible to forego a seal, especially a sealing ring, between the center tube element and the screen support.
[0057] In the following, the outer embodiments of additional inventive water separator elements are described that have on their exterior additional electrically conductive shorting bridges for electrically bridging at least two filter housing electrodes arranged or embodied on an interior of the filter housing.
[0058] FIG. 4 a depicts a fourth water separator element 110 . The fourth water separator element 110 has a particle filter medium 112 . The particle filter medium 112 is embodied as a pleated filter. The particle filter medium 112 is enclosed by a first end plate 114 and a second end plate 116 .
[0059] A first water separator element electrode 120 and a second water separator element electrode 122 are arranged on the outwardly facing surface 118 of the first end plate 114 . The first water separator element electrode 120 is connected to the second water separator element electrode 122 by means of a shorting bridge 124 in the form of an electrical lead. The electrical lead in the present case is embodied in the form of a metal strip.
[0060] FIG. 4 b illustrates a second filter housing 126 for receiving the fourth water separator element 110 according to FIG. 4 a . The second filter housing 126 has a filter housing interior 128 . The filter housing interior 128 faces the fourth water separator element 110 when the fourth water separator element 110 is inserted into the second filter housing 126 .
[0061] A first filter housing electrode 130 and a second filter housing electrode 132 are arranged on the filter housing interior 128 . The first filter housing electrode 130 is embodied radially symmetrical to the longitudinal axis of the second filter housing 126 . In addition, the second housing electrode 132 is embodied radially symmetrical to the longitudinal axis of the second filter housing 126 . The second filter housing electrode 132 is embodied concentric with the first filter housing electrode 130 . In other words, the first filter housing electrode 130 and the second filter housing electrode 132 are embodied essentially in a tire shape or annularly with a common center point. The first filter housing electrode 130 comprises an electrically conductive material, preferably metal. In addition, the second filter housing electrode 132 comprises an electrically conductive material, preferably metal.
[0062] FIG. 4 c depicts a second filter 134 . The second filter 134 has the second filter housing 126 with fourth water separator element 110 therein, compared to “head down” as illustrated for FIG. 4 a . The term “head down” shall be construed as a 180° rotation, the axis of rotation for this rotation running perpendicular to the longitudinal axis of the fourth water separator element 110 . As may be seen from FIG. 1 c , segments of the first water separator element electrode 120 and of the second water separator element electrode 122 are embodied curved. The first water separator element electrode 120 and the second water separator element electrode 122 thus have resilient properties. When fourth water separator element 110 is installed in the second filter housing 126 , the first water separator element electrode 120 is in electrical and mechanical contact with the first filter housing electrode 130 . When fourth water separator element 110 is installed in the second filter housing 126 , the second water separator element electrode 122 is in electrical and mechanical contact with the second filter housing electrode 132 .
[0063] A voltage may be applied between the first filter housing electrode 130 and the second filter housing electrode 132 . Then a current flows from the first filter housing electrode 130 to the first water separator element electrode 120 , via the shorting bridge 124 (see FIG. 1 a ), to the second water separator element electrode 122 and further to the second filter housing electrode 132 . Depending on the polarity of the applied voltage, the current may also flow in the opposing direction. The current only flows if the fourth water separator element 110 is correctly installed in the second filter housing 126 . Thus, by measuring the current flow, it is possible to discern that the fourth water separator element 110 is correctly installed in the second filter housing 126 .
[0064] The current circuit described in the foregoing may furthermore have a known resistance. By measuring this resistance, it is easy to evaluate whether the fourth water separator element 110 is an original part or an imitation. Moreover, the current circuit described in the foregoing may have a known capacity and/or inductivity. By applying an alternating voltage between the first filter housing electrode 130 and the second filter housing electrode 132 , and by measuring the resultant current, it is possible to precisely evaluate whether the fourth water separator element 110 is an imitation.
[0065] If a control element (not shown) detects that there is an imitation or that the fourth water separator element 110 is not correctly installed in the second filter housing 126 , a visual or acoustic indication thereof may be provided to a user. If the second filter 134 is used in a motor vehicle, the engine management system may be interrupted in order to prevent damage to the motor vehicle.
[0066] FIG. 5 a depicts a fifth water separator element 136 . The fifth water separator element 136 corresponds to the fourth water separator element 110 according to FIG. 4 a . In contrast to the fourth water separator element 110 , the fifth water separator element 136 has a shorting bridge 138 that comprises both the first water separator element electrode and the second water separator element electrode, the water separator element electrodes being connected via an electrical lead. The first water separator element electrode and the second water separator element electrode represent different segments of the shorting bridge 138 . The shorting bridge 138 is connected via an elastic water separator element part 140 to a water separator element body 142 of the fifth water separator element 136 . The shorting bridge 138 is embodied from an electrically conductive material, preferably metal.
[0067] FIG. 5 b depicts a third filter 144 . The third filter 144 has the fifth water separator element 136 , which, compared to being “head down” in FIG. 4 a , is built into a third filter housing 146 . The third filter housing 146 has a first filter housing electrode 148 and a second filter housing electrode 150 . A voltage may be applied between the first filter housing electrode 148 and the second filter housing electrode 150 . When the fifth water separator element 136 is installed in the third filter housing 146 , the filter housing electrodes 148 , 150 are electrically bridged by the electrically connected water separator element electrodes of the shorting bridge 138 . Because of this, it is possible to check that the fifth water separator element 136 is correctly seated in the third filter housing 146 . Moreover, it is possible to check whether the fifth water separator element 136 is an imitation.
[0068] The filter housing electrodes 148 , 150 may be embodied radially symmetrical to the longitudinal axis of the third filter housing 146 in order to be able to use the fifth water separator element 136 rotated about its longitudinal axis as desired in the third filter housing 146 .
[0069] The first filter housing electrode 148 and/or the second filter housing electrode 150 may be embodied in the form of an electrically conductive plate, especially a metal plate.
[0070] Alternatively to the third filter housing 146 , the second filter housing 126 according to FIG. 4 b may be used in combination with the fifth water separator element 136 according to FIG. 5 a.
[0071] FIG. 6 a depicts a sixth water separator element 152 . The sixth water separator element 152 corresponds to the fifth water separator element 136 according to FIG. 5 a . In contrast to the fifth water separator element 136 , the sixth water separator element 152 has a shorting bridge 154 in the form of a ring.
[0072] FIG. 6 b depicts a fourth filter housing 156 . The fourth filter housing 156 has a first filter housing electrode 158 and a second filter housing electrode 160 .
[0073] FIG. 6 c depicts a fourth filter 162 . The fourth filter 162 has the fourth filter housing 156 according to FIG. 6 b . The sixth water separator element 152 (according to FIG. 6 a ) of the fourth filter 162 is depicted “head down” in the fourth filter housing 156 . The first filter housing electrode 158 is electrically short circuited with the second filter housing electrode 160 via the shorting bridge 154 . The filter housing electrodes 158 , 160 are embodied in the form of spring pins. The spring pins have elastic filter housing parts (not shown). A particularly reliable electrical contact is attained using the spring pins.
[0074] FIG. 7 a depicts a seventh water separator element 164 . The seventh water separator element 164 corresponds to the sixth water separator element 152 according to FIG. 6 a . In contrast to the sixth water separator element 152 , the seventh water separator element 164 has a first water separator element electrode ring 166 that annularly surrounds an end plate 168 of the seventh water separator element 164 at its exterior circumference. In different segments, the water separator element electrode ring 166 comprises a first water separator element electrode, a second water separator element electrode, and a direct electrical connection in the form of a shorting bridge between these water separator element electrodes.
[0075] FIG. 7 b depicts a fifth filter housing 170 . The fifth filter housing 170 has a first filter housing electrode 172 and a second filter housing electrode 174 .
[0076] FIG. 7 c depicts a fifth filter 176 . The fifth filter 176 comprises the fifth filter housing 170 according to FIG. 7 b and the seventh water separator element 164 according to FIG. 7 a . The seventh water separator element 164 is depicted “head down” in the fifth filter housing 170 . When installed, the water separator element electrode ring 166 bridges the filter housing electrodes 172 , 174 (see FIG. 7 b ; only the first filter housing electrode 172 is visible in FIG. 7 c ). It may be seen from FIG. 7 c that the first filter housing electrode 172 is connected to a filter housing body 180 of the fifth filter housing 176 via an elastic filter housing part 178 . The electrical connection between the filter housing electrodes 172 , 174 and the water separator element electrodes of the water separator element electrode ring 166 is thus even retained after the seventh water separator element 164 has been installed and uninstalled multiple times. The second filter housing electrode (not shown) is also connected to the filter housing body 180 of the fifth filter housing 176 via an elastic filter housing part (not shown).
[0077] FIG. 8 depicts an eighth water separator element 182 . The eighth water separator element 182 has an end plate 184 . A shorting bridge in the form of a contact strip 186 made of metal is embodied on the end plate 184 . The contact strip 186 may be present, for instance, in the form of a metal film. The contact strip 186 has a first water separator element electrode 188 and a second water separator element electrode 190 . The water separator element electrodes 188 , 190 are directly electrically connected via an ohmic lead 192 . The ohmic lead 192 is embodied in the form of a segment of the contact strip 186 .
[0078] FIG. 9 depicts a ninth water separator element 194 . The ninth water separator element 194 corresponds to the eight water separator element 182 . However, a segment of the contact strip 198 , embodied as an ohmic lead 196 , covered by the plastic of an end plate 200 , is inserted in the end plate 200 . Because of this the ohmic lead 196 is less susceptible to damage.
[0079] In summary, the invention preferably relates to a multistage water separator element. The water separator element preferably has a particle filter medium, a coalescer medium, a sedimentation opening, and a screen support having a final separator screen. Preferably two water level electrodes are arranged on the screen support. The water level electrodes are embodied such that they project into a water collection chamber of a filter housing when the water separator element is installed in the filter housing. Each water level electrode may be contacted via one contact electrode that is preferably essentially annular. The contact electrodes may be contacted using tapping electrodes of a center tube element. In this case, the screen support preferably has, in the water separator element longitudinal direction toward the water level electrodes, a closed receiving shaft for the center tube element so that it is not necessary to provide a seal between center tube element and screen support. | A water separator element ( 14 ) for a fuel filter ( 10 ) having two water level electrodes ( 34, 36 ) for detecting backed-up water in a water collection chamber ( 32 ) of the fuel filter ( 10 ). The water level electrodes ( 34, 36 ) can be electrically contacted by means of two contact electrodes ( 40, 42 ), said contact electrodes ( 40, 42 ) being connected in an electrically conductive manner to the water level electrodes ( 34, 36 ). The disclosure further relates to a fuel filter comprising a water separator element of this type. | 1 |
SUMMARY OF THE INVENTION
This is a continuation-in-part of co-pending application Ser. No. 387,065 filed June 10, 1982 (allowed) now U.S. Pat. No. 4,459,423 which is a division of application, Ser. No. 233,521, filed Feb. 11, 1981 now (U.S. Pat. No. 4,375,475) which, in turn, is a continuation-in-part of Ser. No. 140,323 (abandoned) filed Apr. 14, 1980, which in turn is a continuation-in-part of application Ser. No. 067,574, filed Aug. 1, 1979 (now abandoned).
This invention relates to new hypocholesterolemic and hypolipemic compounds having the structure (I) ##STR2## and the corresponding dihydroxy acids resulting from the hydrolytic opening of the lactone ring, and the pharmaceutically acceptable salts of said acids, and the lower alkyl and phenyl, dimethylamino or acetylamino-substituted lower alkyl esters of said dihydroxy acids; all of the compounds being the enantiomers having a 4(R) configuration in the tetrahydropyran moiety of the trans racemate shown in formula I.
BACKGROUND OF THE INVENTION
It is known that certain mevalonate derivatives inhibit the biosynthesis of cholesterol, cf F. M. Singer, et al., Proc. Soc. Exper. Biol. Med., 102, 270 (1959) and F. H. Hulcher, Arch. Biochem. Biophys., 146, 422 (1971), Nevertheless, the activity of these known compounds has not always been found to be satisfactory, i.e. to have practical application.
Recently, Endo et al, reported (U.S. Pat. No. 4,049,495, U.S. Pat. No. 4,137,322 and U.S. Pat. No. 3,983,140) the production of a fermentation product which was quite active in the inhibition of cholesterol biosynthesis. This natural product, now called compactin, was reported by Brown et al., (J. Chem. Soc. Perkin I, 1165 (1976)) to have a complex mevalonolactone structure.
A recent Belgian Pat. No. 867,421 disclosed a group of synthetic compounds of the generic formula II ##STR3## in which E represents a direct bond, a C 1-3 alkylene bridge or a vinylene bridge and the various R's represent a variety of substitutents.
The activity reported in the Belgian patent is less than 1% that of compactin.
DETAILED DESCRIPTION OF THE INVENTION
This invention relates to new hypocholesterolemic and hypolipemic compounds having the structure (I) ##STR4## wherein A is H or methyl;
E is a direct bond, --CH 2 --, --CH 2 --CH 2 --, --CH 2 --CH 2 --CH 2 -- or --CH═CH--;
R 1 , R 2 and R 3 are each selected from
H,
halogen,
C 1-4 alkyl,
C 1-4 haloalkyl,
phenyl,
phenyl substituted by halogen,
C 1-4 alkoxy
C 2-8 alkanoyloxy
C 1-4 alkyl, or
C 1-4 haloalkyl, and
OR 4 in which R 4 is
H,
C 2-8 alkanoyl,
benzoyl,
phenyl,
halophenyl,
phenyl C 1-3 alkyl,
C 1-9 alkyl,
cinnamyl,
C 1-4 haloalkyl,
allyl,
cycloalkyl-C 1-3 -alkyl,
adamantyl-C 1-3 -alkyl, or
substituted phenyl C 1-3 -alkyl in each of which the substituents are selected from
halogen,
C 1-4 alkoxy
C 1-4 alkyl, or
C 1-4 haloalkyl;
and the corresponding dihydroxy acids resulting from the hydrolytic opening of lactone ring, and the pharmaceutically acceptable salts of said acids, and the C 1-3 alkyl and phenyl, dimethylamino or acetylamino-substituted-C 1-3 -alkyl esters of the dihydroxy acids; all of the compounds being the enantiomers having a 4 R configuration in the tetrahydropyran moiety of the trans racemate shown in formula I.
A preferred embodiment of this invention relates to those structures of general formula I
wherein
A is H or methyl;
E is --CH═CH--, or --CH 2 CH 2 --;
R 1 , R 2 and R 3 are each selected from halogen,
C 1-4 alkyl,
C 1-4 haloalkyl,
substituted phenyl in which the substituent is
halo,
C 1-4 alkyl,
C 1-4 alkoxy, and
R 4 O in which R 4 is
phenyl,
halophenyl,
or
substituted phenyl-C 1-3 -alkyl
wherein the substituents are selected from
halogen and
C 1-4 haloalkyl;
and the corresponding dihydroxy acids resulting from the hydrolytic opening of the lactone ring and the pharmaceutically acceptable salts of the dihydroxy acids, and the C 1-3 alkyl and phenyl, dimethylamino or acetylamino-substituted-C 1-3 alkyl esters of the dihydroxy acids; all of the compounds being the enantiomer having a 4 R configuration in the tetrahydropyran moiety of the trans racemate shown in general formula I.
A more preferred embodiment of the present invention comprises those structures of general formula I wherein
A is H or methyl;
E is --CH 2 CH 2 -- or --CH═CH--;
R 1 is situated in the 6-position and is a substituted phenyl wherein there are 1 or 2 substituents and they are independently selected from chloro, fluoro, methyl and methoxy; and
R 2 and R 3 are halo, especially chloro, or C 1-3 alkyl, especially methyl, in the 2 and 4 positions;
and the corresponding dihydroxy acids resulting from the hydrolytic opening of the lactone ring, and the pharmaceutically acceptable salts of the dihydroxy acids, and the C 1-3 alkyl and phenyl, dimethylamino or acetylamino-substituted --C 1-3 alkyl esters of the dihydroxy acids; all of the compounds being the enantiomer having a 4 R configuration in the tetrahydropyran moiety of the trans racemate shown in general formula I.
The compounds in which A is hydrogen, are especially to be preferred. It is also especially preferred that E is --CH═CH--.
The designation 4 R with respect to these compounds indicates that the absolute configuration in space at the 4-carbon of the pyranone ring is believed to be the Rectus (R) series. All the compounds synthesized in the (R) series have been found to be dextrorotatory.
It also has been found that the enantiomers of the trans compounds of Formula I having a 4 R configuration in the tetrahydropyran moiety, especially those in which A is hydrogen, E is --CH═CH-- and R 1 and R 2 are Cl or --CH 3 in the 2 and 4 position and R 3 is substituted-phenyl in the 6 position, as described, are unexpectedly potent inhibitors of cholesterol biosynthesis, approaching and, in many instances, surpassing the order of magnitude of compactin.
While the compounds of Formula I in which A is methyl are 4-R enantiomers of the trans racemates of the compounds of the cited Belgian patent, the latter prior art shows no recognition of the stereochemistry of these compounds, let alone the fact that an unexpectedly large improvement in the activity would result from the separation of the cis and trans racemates and the latter's resolution, especially when the preferred 2,4,6-trisubstitution occurs in the phenyl ring. However, it has been found that the 4 R enantiomers of the trans racemates corresponding to formula I specifically inhibit with high potency the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, which is known to be the enzyme involved in the rate limiting step in the process of cholesterol biosynthesis.
The inhibitory activity of these compounds for the biosynthesis of cholesterol has been measured by two methods. The experimental method A was the in vitro method of H. J. Knauss, et al., J. Biol. Chem., 234, 2835 (1959) and the activity was expressed as the molar concentration IC 50 (M) necessary for the inhibition of 50% of the enzymatic activity. The experimental method B was the method of A. A. Kandutsch, et al., J. Biol. Chem., 248, 8403 (1973) for measuring the quantity of 14 C-cholesterol biosynthesis from acetic acid- 14 C in mouse L cells. The activity is expressed for inhibition of 50% of the biosynthesis of cholesterol.
The results obtained in these two assays, as reported in the cited Belgian patent, show IC 50 values of 10 -4 to 10 -6 in both tests. The smallest 50% effective dose cited is about 4×10 -6 , whereas the value for compactin, in the same tests, is about 0.8×10 -8 . We have found that the inhibitory potency is greatly increased by separation of isomers especially when this is combined with optimal selection of a 2,4,6-arrangement of R 1 , R 2 and R 3 in the phenyl ring and especially when A is hydrogen and E is --CH═CH--. Thus the (+) trans enantiomer of 6-[2-(2,4-dichloro-6-(phenylmethoxy)phenyl)ethyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (Example 14) (a preferred compound of this invention) gives an IC 50 of 6.8×10 -8 in the test by method A. An even more potent and preferred compound of this invention, the (+) trans enantiomer of (E)-6-[2-(3,5 -dichloro-4'-fluoro[1,1'-biphenyl]-2-yl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (Example 43) gives an IC 50 of about 1.3×10 -8 , a potency greater than that of compactin,
Other preferred compounds are: 6-[2-(4'-fluoro-3,3',5-trimethyl[1,1'-biphenyl]-2-yl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (IC 50 =7×10 -9 ); 6-[2-(5-chloro-4'-fluoro-3,3'-dimethyl-[1,1'-biphenyl]-2-yl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one(IC 50 =6×10 -9 ); and 6-[2-(3,3',5,5'-tetramethyl-[1,1'-biphenyl]-2-yl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (IC 50 =1.5×10 -8 ). The compounds were tested as the sodium salts of their corresponding hydroxy acid forms.
The preparation of the compounds of this invention is illustrated in the Flow Sheets.
Flow Sheet I shows the general scheme for synthesizing compounds with a vinylene bridge between the lactone and benzene rings. A starting benzaldehyde is converted to the corresponding cinnamaldehyde (this forms the bridging group) and this is subjected to an aldol reaction to elaborate a hydroxy keto ester from the terminal aldehydic moiety. Reduction of the hydroxy keto ester affords the dihydroxy ester which, upon saponification and subsequent lactonization, gives the lactone. The lactone is then separated chromatographically into its cis and trans racemates and the latter racemate is resolved to give the desired 4 R trans enantiomer.
Flow Sheet II shows the further conversion of the 4 R trans lactones into corresponding dihydroxy acids and their salts and esters. Although this sequence is shown with the --CH═CH-- bridged compounds, the same sequence can be used to give the corresponding acids, salts and esters of any of the other bridged compounds.
Flow Sheet III shows the synthetic routes for the preparation of the alternative bridging groups, represented by E in formula I. Compounds with a direct bond between the lactone and phenyl rings are made by the process of Flow Sheet I with omission of step 2. In this instance, the starting benzaldehyde is used directly in the Aldol reaction. Compounds with a methylene (--CH 2 --) bridge are prepared by starting with the appropriate phenylacetaldehyde in place of the cinnamaldehyde. Compounds with an ethylene (--CH 2 --CH 2 --) bridge between the rings are prepared by reduction of the vinylene bridged compounds prepared in Flow Sheet I. Compounds with a trimethylene bridge (--CH 2 --CH 2 --CH 2 --) are prepared by starting with the appropriate 1-bromo-3-phenylpropane. Compounds of formula I wherein A is a methyl group are prepared as indicated in Flow Sheet IV. Starting with the appropriate aldehyde, condensation with 1-(tri-n-butylstannyl)propan-2-one affords a β-hydroxy ketone which can be converted to the target lactones either by (a) acylation with 2-bromoacetyl bromide followed by intramolecular Reformatsky cyclization or (b) acylation with acetyl chloride followed by intermolecular Reformatsky reaction with ethyl 2-bromoacetate followed by saponification and subsequent lactonization of the resulting dihydroxy acid. Separation of the cis and trans racemic lactones and the subsequent resolution of the trans racemate to obtain the 4 R enantiomer are carried out as described in Flow Sheet I.
Flow Sheet V shows the details of the synthesis of benzaldehydes having an ortho phenyl group, followed by their use in the general scheme of Flow Sheet I to form compounds of this invention. This Flow Sheet summarizes the use of the benzaldehydes so made in the synthesis of vinylene bridged compounds as in Flow Sheet I, but they obviously can also be used as described in Flow Sheet III to produce compounds with other bridging groups. Because of the extremely high potency of the tetrahydropyranones having a 6-(6-phenyl)phenyl group, these compounds, prepared as in Flow Sheet V, are especially to be preferred.
Flow Sheet VI shows an alternate preparation of the 6-phenyl substituted benzaldehydes IIIa. The imines formed between aniline and substituted benzaldehydes are treated with palladium (II) acetate to give stable complexes. These complexes are reacted with substituted phenyl Grignard reagents in the presence of triphenylphosphine to give, after acidic hydrolysis, the 6-phenyl substituted benzaldehydes IIIa. ##STR5##
REACTIONS IN FLOW SHEETS I-VI
1. When R 1 , R 2 or R 3 is HO-- or bears a hydroxyl substituent, the HO-- group is etherified using a reagent R 4 X in a suitable solvent such as DMF and the like in the presence of a suitable base, preferably an alkali metal carbonate such as K 2 CO 3 , to give the corresponding ether R 4 O-- which can be carried through the remainder of the synthesis. If it is desired to remove R 4 at a later synthetic step, R 4 is chosen as an easily removable group such as CH 3 OCH 2 CH 2 OCH 2 -- (the MEM protecting group). The MEM group is removed readily by treatment with a Lewis acid catalyst such as ZnBr 2 in a suitable solvent such as CH 2 Cl 2 and the like. When the starting material is devoid of a hydroxyl group, step (1) is omitted.
2. Aldol Reaction. This can be run in several ways:
(a) The classical Aldol synthesis in which acetaldehyde is condensed with the starting benzaldehyde, the resulting β-hydroxyaldehyde is acetylated with acetic anhydride and acetic acid is eliminated thermally to give the corresponding cinnamaldehyde.
(b) The directed Aldol condensation in which the anion of an appropriately N-substituted ethylidenylimine, such as ethylidenecyclohexylimine and the like, is condensed with the starting benzaldehyde at or below room temperature in an aprotic solvent, such as THF and the like, to afford a β-hydroxy-β-phenylpropylidenylimine which, upon concomitant dehydration and imine hydrolysis in an acidic medium, such as dilute aqueous HCl, provides the corresponding cinnamaldehyde.
(c) The use of a nucleophilic acetaldehyde equivalent in which cis-2-ethoxyvinylithium, generated from cis- 1-ethoxy-2-tri-n-butylstannylethylene, is condensed with the starting benzaldehyde to give an allylic alcohol which is subsequently rearranged, under suitable acidic conditions, to the corresponding cinnamaldehyde.
(3) Dianion Step. Reaction with the dianion of acetoacetic ester in a suitable aprotic solvent such as THF, dioxane and the like.
(4) Reduction with NaBH 4 in a suitable solvent such as methanol, ethanol and the like at or below room temperature.
(5) Lactonization. Saponification by base (e.g. NaOH) in aqueous alcohol followed by acidification and cyclodehydration by heating in toluene.
NOTE: Steps 3, 4 and 5 are usually carried out sequentially without purification of compounds V and VI.
(6) Separation of the cis and trans racemic mixtures by chromatography on silica gel or crystallization.
(7) Resolution of the trans racemate into its enantiomers by treating the (±)-trans lactone with either d-(+) or 1-(-)-α-methylbenzylamine to give the diastereomeric dihydroxy amides which are separated by chromatography or crystallization. Hydrolysis of each pure diastereomeric amide under basic conditions, such as ethanolic NaOH and the like, affords the corresponding enantiomerically pure dihydroxy acid which, upon lactonization, e.g., in refluxing toluene, provides the pure (+)-trans or (-)-trans enantiomer. Stereochemistry depends on the absolute stereochemistry of the diastereomeric amide from which it is derived.
(8) Saponification with M +- OH where M + is an alkali metal cation.
(9) Careful acidification.
(10) Mild hydrolysis
(11) Nucleophilic opening of the lactone ring with an alcohol, R 5 OH, in the presence either of a basic catalyst, particularly the corresponding alkoxide, R 5 O - , or an acidic catalyst such as an acidic ion exchange resin, e.g. Amberlite 120.
(12) Hydrogenation in the presence of a suitable catalyst such as Rhodium or Palladium on carbon.
(13) Reaction with NaCN in a suitable solvent such as aqueous ethanol and the like.
(14) Reduction with DIBAL in an aprotic solvent such as toluene, ether and the like followed by work up with an aqueous acid such as 5% H 2 SO 4 .
(15) Aldol condensation with 1-(tri-n-butyl stannyl)propan-2-one.
(16) Acylation with 2-bromoacetyl bromide.
(17) Intramolecular Reformatsky reaction carried out, for example, in the presence of activated zinc dust, cuprous bromide and diethylaluminum chloride.
(18) Acylation with acetyl chloride.
(19) Intermolecular Reformatsky reaction carried out with ethyl 2-bromoacetate, for example, in the presence of the reagents indicated in step (17) above.
(20) Treatment with N-bromosuccinimide in CCl 4 with irradiation by a sun lamp (Tetrahedron Letters, 3809 (1979)).
(21) Treatment with two equivalents of the amine ##STR6##
(22) Reaction with SOCl 2 (J. Org. Chem., 43, 1372 (1978)).
(23) Reaction with a substituted phenyl Grignard reagent ##STR7##
(24) Reaction with methyl iodide in a suitable solvent such as acetone.
(25) Reaction with NaBH 4 in a suitable solvent such as ethanol or methanol.
(26) Heating with acid (J. Het. Chem., 3, 531 (1966)).
(27) Reaction with Palladium (II) acetate in acetic acid at reflux.
(28) Reaction with a substituted Grignard reagent ##STR8## in suitable solvents such as benzene or toluene in the presence of triphenylphosphine
(29) Hydrolysis with 6N HCl at ambient temperature.
A further aspect of the present invention is a pharmaceutical composition consisting of at least one of the compounds of formula I in association with a pharmaceutical vehicle or diluent. The pharmaceutical composition can be formulated in a classical manner utilizing solid or liquid vehicles or diluents and pharmaceutical additives of a type appropriate to the mode of desired administration. The compounds can be administered by an oral route, for example, in the form of tablets, capsules, granules or powders, or they can be administered by a parenteral route in the form of injectable preparations. The dose to be administered depends on the unitary dose, the symptoms, and the age and the body weight of the patient. A dose for adults is preferably between 200 and 2,000 mg per day, which can be administered in a single dose or in the form of individual doses from 1-4 times per day.
A typical capsule for oral administration contains active ingredient (250 mg), lactose (75 mg) and magnesium stearate (15 mg). The mixture is passed through a 60 mesh sieve and packed into a No. 1 gelatin capsule.
A typical injectible preparation is produced by asceptically placing 250 mg of sterile active ingredient into a vial, asceptically freeze-drying and sealing. For use, the contents of the vial are mixed with 2 ml of physiological saline, to produce an injectible preparation.
The compounds of this invention also have useful antifungal activities. For example, they may be used to control strains of Penicillium sp., Aspergillus niger, Cladosporium sp., Cochliobolus miyabeorus and Hilminthosporium cynodnotis. For those utilities they are admixed with suitable formulating agents, powders, emulsifying agents or solvents such as aqueous ethanol and sprayed or dusted on the plants to be protected.
This invention can be illustrated by the following examples in which ratios of solvents are in volumes and percentages, unless otherwise indicated, or by weight.
EXAMPLE 1
Preparation of (E)-6-[2-(2,4-Dichloro-6-(phenylmethoxy)phenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
Step A. Preparation of 2,4-Dichloro-6-phenylmethoxybenzaldehyde
Potassium carbonate (9.4 g, 67.8 mmole) was added to a stirred solution of 4,6-dichlorosalicylaldehyde (10.8 g, 56.5 mmole) in dimethylformamide (80 ml). The resulting mixture was stirred at 60° for 30 minutes and treated with benzyl bromide (10.6 g, 62.1 mmole). This mixture was stirred one hour at 60° C. and then poured into ice water (1000 ml) to give the title compound (15.9 g, 100%) which melted at 98°-100° C. after recrystallization from hexane. pmr (CDCl 3 ) δ 5.10 (2H, s), 7.33 (5H, s), 10.40 (H, s).
Analysis Calc. for C 14 H 10 Cl 2 O 2 . Calc.: C, 59.81; H, 3.58. Found: C, 59.98; H, 3.58.
Step B. Preparation of (E)-2,4-Dichloro-6-phenylmethoxycinnamaldehyde
A stirred suspension of 2,4-dichloro-6-phenylmethoxybenzaldehyde (15.5 g, 55.1 mmole) in acetaldehyde (30 ml) was cooled to 5° C. and treated with 25% methanolic potassium hydroxide (1.4 ml, 6.24 mmole) at such a rate that the internal temperature was maintained at 25°-30° C. The resulting solution was stirred for 30 minutes in the ice bath, treated with acetic anhydride (30 ml) and then heated at 100° C. for 30 minutes. After cooling to 30° C. the solution was treated with water (84 ml) and 12N hydrochloric acid (7 ml). The resulting mixture was refluxed for 30 minutes and then cooled in an ice bath to give a gummy solid which was recrystallized from cyclohexane to give the title compound (5.6 g, 33%), mp 109°-112° C.: pmr (CDCl 3 ) δ 5.10 (2H, s), 7.33 (5H, s), 9.68 (H, d).
Analysis Calc. for C 16 H 12 Cl 2 O 2 . Calc. C, 62.56; H, 3.94. Found: C, 62.66; H, 3.98.
Alternate Step B. Preparation of (E)-2,4-Dichloro-6-phenylmethoxycinnamaldehyde
A 1.6M solution (18.8 ml, 30 mmole) of n-butyllithium in hexane was added cautiously to a stirred solution of freshly distilled diisopropylamine (3.0 g, 30 mmole) in anhydrous tetrahydrofuran (200 ml) maintained at 0° C. under a nitrogen atmosphere. The resulting solution was stirred at 0° C. for 15 minutes and then treated with ethylidenecyclohexylamine (3.75 g, 30 mmole). The solution was stirred 15 minutes at 0° C., cooled to -78° C. and treated with a solution of 2,4-dichloro-6-phenylmethoxybenzaldehyde (8.4 g, 30 mmole) in anhydrous tetrahydrofuran (50 ml). The resulting red solution was stirred at -78° C. for 15 minutes and then at 25° C. for 60 minutes. The reaction solution was treated with water (200 ml) and extracted with ether (3×200 ml). The organic extracts were combined, washed with brine (3×100 ml), dried over magnesium sulfate and filtered. The filtrate was evaporated in vacuo, leaving the desired intermediate hydroxyimine as a brown viscous oil (12.5 g): pmr (CDCl 3 )δ5.10 (2H, s), 5.50 (H, t), 7.37 (5H, s), 7.70 (H, s).
A solution of the oily imine (12.5 g) in tetrahydrofuran (110 ml) was treated with a solution of oxalic acid dihydrate (11 g, 87.2 mmole) in water (22 ml). The resulting solution was refluxed for 30 minutes, cooled to 25° C. and poured into water (500 ml). The resulting mixture was extracted with ether (3×200 ml). The organic extracts were combined, washed with brine (3×50 ml), dried over magnesium sulfate and filtered. The filtrate was evaporated in vacuo, leaving the title compound as a tan solid. The title compound was purified by recrystallization from cyclohexane to give yellow needles (4.7 g, 51%) melting at 109°-111° C.: pmr (CDCl 3 ) δ5.11 (2H, s), 7.33 (5H, s), 9.68 (H, d).
Alternate to Alternate Step B. Preparation of (E)-2,4-Dichloro-6-phenylmethoxycinnamaldehyde
A 1.37M solution (24.1 ml, 33 mmole) of n-butyllithium in hexane was added cautiously to a stirred solution of cis-1-ethoxy-2-tri-n-butylstannylethylene (11.9 g, 33 mmole) in anhydrous tetrahydrofuran (75 ml) maintained at -78° C. under a nitrogen atomosphere. The resulting solution was stirred at -78° C. for one hour and then treated with a solution of 2,4-dichloro-6-phenylmethoxybenzaldehyde (8.4 g, 30 mmole) in anhydrous tetrahydrofuran (50 ml). The resulting brown solution was stirred at -78° C. for one hour and then allowed to warm to 20° C. The reaction solution was quenched with saturated aqueous sodium bicarbonate (25 ml), diluted with water (100 ml) and then extracted with ether (2×200 ml). The organic extracts were combined, washed with brine (2×100 ml), dried over magnesium sulfate and filtered. The filtrate was evaporated in vacuo, leaving the desired intermediate allylic alcohol as a yellow oil.
The oil was chromatographed on a silica column (400 g) to cause allylic rearrangement to the desired product. Elution with methylene chloride (200 ml) provided a forerun containing tetrabutyltin which was discarded. Continued elution with methylene chloride/methanol (98:2, v:v; 1500 ml) gave the title compound as a pale yellow solid, mp 109°-111° C. (6.4 g, 70%).
Step C. Preparation of Methyl (E)-7-(2,4-dichloro-6-phenylmethoxyphenyl)-5-hydroxy-3-oxo-6-heptenoate
Methyl acetoacetate (9.56 g, 82.3 mmole) was added dropwise to a stirred suspension of sodium hydride (50% oil suspension) (3.95 g, 82.3 mmole) in anhydrous tetrahydrofuran at 0° C. under a nitrogen atmosphere. The resulting solution was stirred 15 minutes at 0° C. and then treated with a 1.6M solution (51.5 ml, 82.3 mmole) of n-butyllithium in hexane over 5 minutes. The resulting yellow solution was stirred 15 minutes at 0° C. and then treated with a solution of (E)-2,4-dichloro-6-phenylmethoxycinnamaldehyde (25.3 g, 82.3 mmole) in anhydrous tetrahydrofuran (150 ml). The resulting orange solution was stirred 15 minutes at 0° C. and then quenched by dropwise addition of 12N hydrochloric acid (ca. 20 ml). The reaction mixture was diluted with water (100 ml) and extracted with ether (3×300 ml). The organic extracts were combined, washed with brine (3×100 ml), dried over magnesium sulfate and filtered. The filtrate was evaporated in vacuo leaving the title compound as a yellow oil (34.8 g, 100%): pmr (CDCl 3 ) δ2.75 (2H, d), 3.45 (2H, s), 3.72 (3H, s), 4.71 (H, m), 5.50 (2H, s), 7.37 (5H, s).
Step D. Preparation of Methyl (E)-7-(2,4-Dichloro-6-phenylmethoxyphenyl)-3,5-dihydroxy-6-heptenoate
Sodium tetrahydridoborate (1.55 g, 41.1 mmole) was added with stirring to a cooled solution (5° C.) of methyl (E)-7-(2,4-dichloro-6-phenylmethoxyphenyl)-5-hydroxy-3-oxo-6-heptenoate (34.8 g, 82.3 mmole) in ethanol (200 ml) at a rate sufficient to maintain the internal temperature at 15°-20° C. The resulting solution was stirred with ice-bath cooling for 15 min. and then acidified with 6N hydrochloric acid. The resulting mixture was diluted with water (500 ml) and extracted with ether (3×250 ml). The organic extracts were combined, washed with brine (4×100 ml), dried over magnesium sulfate and filtered. The filtrate was evaporated in vacuo, leaving the title compound as a yellow oil (34.8 g, 99.5%): pmr CDCl 3 ) δ2.45 (2H, d), 3.65 (3H, s), 4.18 (H, m), 4.45 (H, m), 4.98 (2H, s), 7.28 (5H, s).
Step E. Preparation of (E)-7-(2,4-Dichloro-6-phenylmethoxyphenyl)-3,5-dihydroxy-6-heptenoic acid
A solution of methyl (E)-7-(2,4-dichloro-6-phenylmethoxyphenyl)-3,5-dihydroxy-6-heptenoate (34.8 g, 81.8 mmole), 1N sodium hydroxide (82 ml, 82 mmole) and ethanol (200 ml) was stirred at 25° C. for 15 min. The reaction solution was acidified with 6N hydrochloric acid, diluted with water (400 ml) and extracted with ether (3×200 ml). The combined organic extracts were washed with brine (3×100 ml), dried over magnesium sulfate and filtered. The filtrate was evaporated in vacuo, leaving the title compound as an orange oil (33.3 g, 99%): pmr (CDCl 3 )δ2.47 (2H, d), 4.30 (2H, br m), 4.98 (2H, s), 7.30 (5H, s).
Step F. Preparation of (E)-6-[2-(2,4-Dichloro-6-phenylmethoxyphenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
A solution of (E)-7-(2,4-dichlorophenylmethoxyphenyl)-3,5-dihydroxy-6-heptenoic acid (33.3 g, 81.3 mmole) in toluene (300 ml) was heated at reflux in a Dean-Stark apparatus. After 2 hours the Dean-Stark apparatus was replaced with a soxhlet containing 3 Å molecular sieves (100 g). The solution was refluxed for an additional 4 hours and then the toluene was removed in vacuo leaving a yellow oil (31.7 g) which is a mixture of cis and trans isomers of the title compound. The oil was chromatographed on a silica gel column (900 g). Elution with methylene chloride-acetone (9:1, v:v; 4000 ml) provided a forerun which was discarded. Continued elution with the same eluant (500 ml) gave the trans isomer of the title compound as a pale yellow solid (5.8 g).
Further elution of the column with the same eluant (3250 ml) gave a tan solid (8.8 g), which is a mixture of the cis and trans isomers of the title compound. This cis/trans mixture was chromatographed using a Waters Prep LC500. Separation of this mixture was accomplished by using two prep PAK-500/silica cartridges in series and eluting with methylene chloride-acetone (9:1, v:v). Using the shave recycle technique, the cis (4.7 g) and the trans (3.3 g) isomers of the title compound were obtained. The fractions of the trans isomer, collected from the two chromatographys, were combined and recrystallized from n-butyl chloride to give the trans isomer of the title compound (7.3 g, 23%), mp 130°-131° C.: pmr (CDCl 3 ) δ2.64 (2H, m), 4.30 (H, m), 5.07 (2H, s), 5.30 (H, m), 7.42 L (5H, s).
Analysis Calc. for C 20 H 18 Cl 2 O 4 . Calc.: C, 61.08; H, 4.61. Found: C, 61.12; H, 4.60.
The cis isomer (4.3 g, 13%) of the title compound melted at 130°-131.5° C. after recrystallization from n-butyl chloride: pmr (CDCl 3 ) δ4.30 (H, m), 4.83 (H, m), 5.12 (2H, s), 7.47 (5H, s).
Analysis Calc. for C 20 H 18 Cl 2 O 4 . Calc.: C, 61.08; H, 4.61. Found: C, 61.55; H, 4.63.
EXAMPLE 2
Starting with 4,6-dichlorosalicylaldehyde but substituting equimolar amounts of the following alkyl halide or tosylate in place of benzyl bromide in Step A of Example 1 and following the procedure of Steps A through F there was obtained a corresponding amount of the appropriate end product listed below.
__________________________________________________________________________Alkyl Halide M. P.or Tosylate End Product Isomer °C. Calc. Fd.__________________________________________________________________________ -n-pentyl iodide (E)-6-[2-(2,4-dichloro-6- trans 81-83 C 57.92 57.68 -n-pentyloxyphenyl)ethenyl]- H 5.94 6.01 3,4,5,6-tetrahydro-4- hydroxy-2H--pyran-2-one cis oil C 57.92 57.54 H 5.94 6.093,4-dichlorobenzyl (E)-6-{2-[2,4-dichloro- trans 73-75 C 52.27 52.03chloride 6-(3,4-dichlorophenyl- H 3.73 3.74 methoxy)phenyl]ethenyl}- 3,4,5,6-tetrahydro-4- hydroxy-2H--pyran-2-onediphenylmethyl (E)-6-[2-(2,4-dichloro-6- trans 135.5-137 C 66.53 66.71bromide diphenylmethoxyphenyl) H 4.72 4.63 ethenyl]-3,4,5,6-tetra- hydro-4-hydroxy-2H--pyran- 2-oneallyl bromide (E)-6-[2-(2,4-dichloro-6- trans 82-84 C 55.99 56.14 allyloxyphenyl)ethenyl]- H 4.70 4.70 3,4,5,6-tetrahydro-4- hydroxy-2H--pyran-2-one2-methoxyethoxy- (E)-6-{2-[2,4-dichloro-6- trans oil C 52.19 52.04methyl chloride (2-methoxyethoxymethoxy)- H 5.15 5.05 phenyl]ethenyl}-3,4,5,6- tetrahydro-4-hydroxy-2H-- pyran-2-onemethylthio- (E)-6-[2-(2,4-dichloro-6- trans oil C 49.60 49.97methyl chloride methylthiomethoxyphenyl)- H 4.44 4.74 ethenyl]-3,4,5,6-tetrahydro- 4-hydroxy-2H--pyran-2-one2-(adamant-1- (E)-6-{2-[ 2,4-dichloro-6- trans 174-6 C 64.52 64.38yl)ethyl tol- (2-adamant-1-ylethoxy)- H 6.52 6.70uene-p-sul- phenyl]ethenyl}-3,4,5,6-phonate tetrahydro-4-hydroxy-2H-- pyran-2-one4-chlorobenzyl (E)-6-{2-[6-(4-chloro- trans 111.5-113 C 56.16 56.08bromide phenylmethoxy-2,4- H 4.01 3.98 dichlorophenyl]ethenyl}- 3,4,5,6-tetrahydro-4- hydroxy-2H--pyran-2-one1-bromo-3- (E)-6-{2-[2,4-dichloro-6- trans 93-94 C 62.71 62.66phenylpro- (3-phenylpropoxy)phenyl]- H 5.26 5.25pane ethenyl}-3,4,5,6-tetrahy- dro-4-hydroxy-2H--pyran- 2-one1-bromo-2- (E)-6-[2-(2,4-dichloro-6- trans 125-126 C 61.93 62.18phenyl- phenylethoxyphenyl)ethenyl]- H 4.95 5.07ethane 3,4,5,6-tetrahydro-4- hydroxy-2H--pyran-2-onecinnamyl (E) (E)-6-{2-[2,4-dichloro- trans 120-122 C 63.02 62.73bromide 6-(3-phenyl-2-propenyloxy)- H 4.81 4.81 phenyl]ethenyl}-3,4,5,6- tetrahydro-4-hydroxy-2H-- pyran-2-one1-bromo-3,5,5- (E)-6-{2-[2,4-dichloro-6- trans 53-66 C 61.54 61.60trimethyl- (3,5,5-trimethylhexyl- H 7.04 7.27hexane oxy)phenyl]ethenyl}-3,- 4,5,6-tetrahydro-4- hydroxy-2H--pyran-2- one4-methylbenzyl (E)-6-{2-[2,4-dichloro- trans 113-118 C 61.92 62.05bromide 6-(4-methylphenyl- H 4.95 5.05 methoxy)phenyl]ethenyl}- 3,4,5,6-tetrahydro-4- hydroxy-2H--pyran-2-one4-methoxybenzyl (E)-6-{2-[2,4-dichloro- trans 114-115 C 59.58 59.73bromide 6-(4-methoxyphenyl H 4.76 4.75 methoxy)phenyl]ethenyl} - 3,4,5,6-tetrahydro-4- hydroxy-2H--pyran-2-one4-fluorobenzyl (E)-6-{2-[2,4-dichloro- trans 124-6 C 58.41 58.26bromide 6-(4-fluorophenyl- H 4.17 4.20 methoxy)phenyl]ethenyl}- 3,4,5,6-tetrahydro-4- cis 131-3 C 58.41 58.29 hydroxy-2H--pyran-2-one H 4.17 4.062-fluorobenzyl (E)-6-{2-[2,4-dichloro- trans 140-141.5 C 58.41 58.43chloride 6-(2-fluorophenylmethoxy)- H 4.17 4.20 phenyl]ethenyl}-3,4,5,6- tetrahydro-4-hydroxy-2H-- pyran-2-one2,4-difluorobenzyl (E)-6-{2-[2,4-dichloro-6- trans 138-139 C 55.96 56.00bromide (2,4-difluorophenylmethoxy) H 3.76 3.82 phenyl]ethenyl}-3,4,5,6-tetra- hydro-4-hydroxy-2H--pyran-2- one3-fluorobenzyl (E)-6-{2-[2,4-dichloro-6(3- trans 91.5-92 C 58.41 58.48bromide fluorophenylmethoxy)- H 4.17 4.22 phenyl]ethenyl}-3,4,5,6- tetrahydro-4-hydroxy-2H-- pyran-2-one2,3,4,5,6-penta- (E)-6-{2-[2,4-dichloro-6- trans 72-75 C 49.90 49.87fluorobenzyl- (2,3,4,5,6-pentafluoro- H 3.33 3.35chloride phenylmethoxy)phenyl]- ethenyl}-3,4,5,6-tetrahydro- 4-hydroxy-2H--pyran-2-one. 0.5 chlorobutane__________________________________________________________________________
EXAMPLE 3
By substituting an equimolar amount of 3,5-dichlorosalicylaldehyde for 4,6-dichlorosalicylaldehyde and an equimolar amount of n-pentyl iodide for benzyl bromide in Step A of Example 1 and following the procedure for Steps A through F, there was obtained a corresponding amount of the following end product.
(E)-6-[2-(3,5-Dichloro-2-pentyloxyphenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one, trans isomer: yellow oil.
Analysis calc for C 18 H 22 Cl 2 O 4 . Calc.: C, 57.92; H, 5.94. Found: C, 57.83; H, 5.91.
cis isomer: yellow oil.
Analysis calc. for C 18 H 22 Cl 2 O 4 . Calc.: C, 57.92; H, 5.94. Found: C, 57.54; H, 6.09.
EXAMPLE 4
By substituting an equimolar amount of the following aldehydes in place of 2,4-dichloro-6-phenylmethoxybenzaldehyde in Step B of Example 1 and then following the procedures of Steps B through F, there was obtained a corresponding amount of the appropriate end product listed below.
__________________________________________________________________________ M.P.Aldehyde End Product Isomer °C. Calc. Fd.__________________________________________________________________________2,4-dichloro- (E)-6-[2-(2,4-dichloro- trans 146-148 C 54.37 54.57benzaldehyde phenyl)ethenyl]-3,4,5,6- H 4.21 4.31 tetrahydro-4-hydroxy- cis 115-117 C 54.37 54.24 2H--pyran-2-one H 4.21 3.962,4-dimethyl- (E)-6-[2-(2,4-dimethyl- trans 111-113 C 73.14 73.07benzaldehyde phenyl)ethenyl]-3,4,5,6- H 7.36 7.46 tetrahydro-4-hydroxy- cis 110-112 C 73.14 72.77 2H--pyran-2-one H 7.36 7.572,6-dichloro- (E)-6-[2-(2,6-dichloro- trans 102-104 C 54.37 54.65benzaldehyde phenyl)ethenyl]-3,4,5,6- H 4.21 4.21 tetrahydro-4-hydroxy- cis 118-119 C 54.37 54.37 2H--pyran-2-one H 4.21 4.172-chloro- (E)-6-[2-(2-chlorophenyl)- trans 129-131 C 61.79 61.89benzaldehyde ethenyl]-3,4,5,6-tetra- H 5.18 5.38 hydro-4-hydroxy-2H--pyran- 2-one4-phenyl- (E)-6-[2-(4-biphenyl)- trans 148-150 C 77.53 77.74benzaldehyde ethenyl]-3,4,5,6- H 6.16 6.02 tetrahydro-4-hydroxy- 2H--pyran-2-one__________________________________________________________________________
EXAMPLE 5
By substituting an equimolar amount of the following aldehydes for (E)-2,4-dichloro-6-phenylmethoxycinnamaldehyde in Step C of Example 1 and following the procedure for Steps C through F, there was obtained a corresponding amount of the appropriate end product listed below.
__________________________________________________________________________ M.P.Aldehyde End Product Isomer °C. Calc. Fd.__________________________________________________________________________benzaldehyde 3,4,5,6-tetrahydro-4- trans 91-93 C 68.73 68.56 hydroxy-6-phenyl- H 6.29 6.49 2H--pyran-2-onebenzaldehyde 3,4,5,6-tetrahydro-4- cis 91-93 C 68.73 68.72 hydroxy-6-phenyl- H 6.29 6.41 2H--pyran-2-one(E)-cinnamaldehyde (E)-3,4,5,6-tetrahydro-4- trans 96-98.5 C 71.54 71.41 hydroxy-6-(2-phenylethenyl)- H 6.46 6.59 2H--pyran-2-one(E)-cinnamaldehyde (E)-3,4,5,6-tetrahydro-4- cis 91-92.5 C 71.54 71.79 hydroxy-6-(2-phenylethenyl)- H 6.46 6.53 2H--pyran-2-one4-phenylbenz- 6-(4-biphenyl)-3,4,5,6- trans 135-137 C 76.10 76.28aldehyde tetrahydro-4-hydroxy- H 6.01 5.68 2H--pyran-2-one4-phenylbenz- 6-(4-biphenyl)-3,4,5,6- cis 146-148 C 76.10 76.11aldehyde tetrahydro-4-hydroxy- H 6.01 5.67 2H--pyran-2-one2,4-dichloro- 6-(2,4-dichlorophenyl)- trans 133-136 C 50.60 50.88benzaldehyde 3,4,5,6-tetrahydro-4- H 3.86 3.87 hydroxy-2H--pyran-2-one2,4-dichloro- 6-(2,4-dichlorophenoxy- trans "oil" C 49.51 49.24phenoxyacet- methyl)-3,4,5,6-tetrahydro- H 4.15 4.10aldehyde 4-hydroxy-2H--pyran-2-one__________________________________________________________________________
EXAMPLE 6
Preparation of (E)-6-[2-(2,3-Dichlorophenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
Step A. Preparation of (E)-2,3-Dichlorocinnamaldehyde
Anhydrous aluminum chloride (10.5 g, 78.8 mmole) was slowly added to a stirred solution of 2,3-dichlorobenzoyl chloride (14.4 g, 68.7 mmole) and bis-trimethylsilylacetylene (12.8 g, 75.1 mmole) in dry methylene chloride maintained at 0° C. The dark brown reaction mixture was stirred 5 minutes at 0° C. and 2 hours at 25° C. and then poured into ice water. The organic product was extracted into ether (4×200 ml). The ether extracts were combined, washed with brine (3×100 ml), dried over magnesium sulfate and filtered. The filtrate was evaporated in vacuo leaving the desired intermediate trimethylsilylacetylenic ketone as a brown oil (18.4 g, 98%), pmr (CDCl 3 ) δ0.30 (9H, s), 7.47 (3H, m).
Sodium methoxide (0.81 g, 15.0 mmole) was added to a stirred solution of the oily trimethylsilylacetylenic ketone (18.4 g, 67.8 mmole) in methanol (200 ml) maintained at 0° C. in an ice bath. After 5 minutes the ice bath was removed and the reaction solution was stirred 30 minutes at 25° C. The resulting solution was cooled to 0° C. and sodium tetrahydridoborate (0.9 g, 23.8 mmole) was slowly added. This reaction solution was stirred 30 minutes at 25° C. and then poured into ice water. The organic product was extracted into ether (4×150 ml). The ether extracts were combined, washed with brine (3×100 ml), dried over magnesium sulfate and filtered. The filtrate was evaporated in vacuo, leaving the desired β-hydroxydimethylacetal as a brown oil. Hydrochloric acid (6N, 50 ml) was added to the solution of the crude β-hydroxydimethylacetal in dioxane (100 ml). The resulting mixture was heated on the steam bath for 30 minutes, and then poured into ice water (1000 ml) to give the title compound as a brown solid (12.7 g). This solid was chromatographed on a silica gel column (700 g). Elution with ethyl acetate-hexane (2:8, V:V; 1250 ml) provided a forerun which was discarded. Continued elution with the same eluant (1125 ml) gave the title compound (10.6 g, 78%) which melted at 94°-95° C: pmr (CDCl 3 )δ6.70 (H, dd), 7.98 (H, d), 9.86 (H, d).
Analysis Calc. for C 9 H 6 Cl 2 O. Calc.: C, 53.76; H, 3.01. Found: C, 53.52; H, 2.86.
Step B. Preparation of (E)-6-[2-(2,3-Dichlorophenyl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
By substituting an equimolar amount of (E)-2,3-dichlorocinnamaldehyde for (E)-2,4-dichloro-6-phenylmethoxycinnamaldehyde in Step C of Example 1 and following the procedure for Steps C through F, there was obtained a corresponding amount of the title compound.
trans isomer: mp 122°-123° C.
Analysis Calc. for C 13 H 12 Cl 2 O 3 . Calc.: C, 54.37; H, 4.21. Found: C, 54.31; H, 4.25.
cis isomer: mp 131°-132° C.
Analysis Calc. for C 13 H 12 Cl 2 O 3 . Calc.: C, 54.37; H, 4.21. Found: C, 54.52; H, 4.25.
EXAMPLE 7
Preparation of (E)-6-[2-([1,1'-Biphenyl]-2-yl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
By substituting an equimolar amount of [1,1'-biphenyl]-2-carbonyl chloride for 2,3-dichlorobenzoyl chloride in Step A of Example 6 and following the procedure for Steps A and B, there was obtained a corresponding amount of the title compound.
trans isomer: mp 89°-91° C.
Analysis Calc. for C 19 H 18 O 3 . Calc.: C, 77.53; H, 6.16. Found: C, 77.51; H, 6.17.
cis isomer: yellow glass.
Analysis Calc. for C 19 H 18 O 3 . Calc.: C, 77.53; H, 6.16. Found: C, 77.26; H, 6.07.
EXAMPLE 8
Preparation of Trans-6-[2-(2,4-Dichloro-6-phenylmethoxyphenyl)ethyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
A solution of trans-(E)-6-[2-(2,4-dichloro-6-phenylmethoxyphenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (1.1 g, 28 mmole) in tetrahydrofuran (50 ml) was magnetically stirred and hydrogenated at room temperature and atmospheric pressure in the presence of 110 mg of 5% rhodium on carbon catalyst until 1.5 molar equivalents of hydrogen had been consumed. After removing the catalyst by filtration, the filtrate was evaporated in vacuo leaving the title compound as a pale yellow oil. The oil was chromatographed on a silica gel column (200 g). Elution with acetone-methylene chloride (1:9, v:v; 560 ml) provided a forerun which was discarded. Continued elution with the same eluant (240 ml) gave the title compound as a colorless oil which solidified when it was triturated with ether. The title compound was purified by recrystallization from ether-hexane (1:1, v:v; 20 ml) to give colorless needles (0.67 g, 61%) melting at 99°-101° C.: pmr (CDCl 3 )δ1.83 (4H, m), 2.60 (2H, m), 2.90 (2H, m), 4.30 (H, m), 4.62 (H, m), 5.05 (2H, s), 7.42 (5H, s).
Analysis Calc. for C 20 H 20 Cl 2 O 4 . Calc.: C, 60.77; H, 5.10. Found: C, 60.96; H, 4.85.
EXAMPLE 9
By substituting an equimolar amount of the following 2H-pyran-2-ones for trans-(E)-6-[2-(2,4-dichloro-6-phenylmethoxyphenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one in Example 8 and following the procedure of Example 8, there was obtained a corresponding amount of the following end products.
__________________________________________________________________________ M.P.2H--Pyran-2-one End Product °C. Calc. Fd.__________________________________________________________________________ trans-(E)-6-(2-phenyl- trans-6-(2-phenylethyl)-3,4- 76-77 C 70.88 71.02ethenyl)-3,4,5,6- 5,6-tetrahydro-4-hydroxy-2H-- H 7.32 7.41tetrahydro-4-hydroxy pyran-2-onetrans-(E)-6-[2-(2,4- trans-6-[2-(2,4-dichlorophenyl)- 95-97 C 54.00 53.80dichlorophenyl)- ethyl]-3,4,5,6-tetrahydro-4- H 4.88 4.71ethenyl]-3,4,5,6- hydroxy-2H--pyran-2-onetetrahydro-4-hydroxycis-(E)-6-[2-(2,4- cis-6-[2-(2,4-dichlorophenyl)- oil C 54.00 53.89dichlorophenyl)- ethyl]-3,4,5,6-tetrahydro-4- H 4.88 4.90ethenyl]-3,4,5,6- hydroxy-2H--pyran-2-onetetrahydro-4-hydroxytrans-(E)-6-[2-([1,1'- trans-6-[2-([1,1'-biphenyl]- oil C 77.00 77.17biphenyl]-2-yl)ethenyl]- 2-yl)-ethyl]-3,4,5,6-tetrahydro-4- H 6.80 6.853,4,5,6-tetrahydro- hydroxy-2H--pyran-2-one4-hydroxycis-(E)-6-[2-(2,4- cis-6-[2-(2,4-dichloro-6- 96-98 C 60.77 60.73dichloro-6-phenyl- phenylmethoxyphenyl)ethyl]- H 5.10 5.24methoxyphenyl)ethenyl]- 3,4,5,6-tetrahydro-4-hydroxy-3,4,5,6-tetrahydro-4- 2H--pyran-2-onehydroxytrans-(E)-6-[2-(2,4- trans-6-[2-(2,4-dichloro- 154-155 C 59.85 59.87dichloro-6-cyclohexyl- 6-cyclohexylmethoxyphenyl)- H 6.53 6.44methoxyphenyl)ethenyl]- ethyl]-3,4,5,6-tetrahydro-3,4,5,6-tetrahydro-4- 4-hydroxy-2H--pyran-2-onehydroxytrans-(E)-6-[2-(2,4- trans-6-[2-(2,4-dichloro- oil C 59.85 59.84dichloro-6-phenoxy- 6-phenoxyphenyl)ethyl]- H 4.76 5.10phenyl)ethenyl]- 3,4,5,6-tetrahydro-4-3,4,5,6-tetrahydro- hydroxy-2H--pyran-2-one4-hydroxytrans-(E)-6-{2-[2,4- trans-6-{ 2-[2,4-dichloro- 151-152 C 58.12 58.13dichloro-6-(4-fluoro- 6-(4-fluorophenylmethoxy)- H 4.63 4.68phenylmethoxy)phenyl]- phenyl]ethyl}-3,4,5,6-tetra-ethenyl}-3,4,5,6-tetra- hydro-4-hydroxy-2H--pyran-hydro-4-hydroxy 2-onetrans-(E)-6-{2-[2,4- trans-6-{2-[2,4-dichloro- 98-100 C 58.12 58.24dichloro-6-(2-fluoro- 6-(2-fluorophenylmethoxy)- H 4.63 4.63phenylmethoxy)phenyl]- phenyl]ethyl}-3,4,5,6-tetra-ethenyl}-3,4,5,6-tetra- hydro-4-hydroxy-2H--pyran-hydro-4-hydroxy 2-onetrans-(E)-6-{2-[2,4- trans-6-{2-[2,4-dichloro- 106-115 C 58.12 58.20dichloro-6-(3-fluoro- 6-(3-fluorophenylmethoxy)- H 4.63 4.72phenylmethoxy)phenyl]- phenyl]ethyl}-3,4,5,6-tetra-ethenyl}-3,4,5,6-tetra- hydro-4-hydroxy-2H--pyran-hydro-4-hydroxy 2-one__________________________________________________________________________
EXAMPLE 10
Preparation of (E)-6-[2-(3,4-Dichlorophenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
Step A. Preparation of (E)-3,4-Dichlorocinnamaldehyde
The reaction mixture containing sodium tetrahydrodiborate (0.76 g, 20 mmole), cadmium chloride. 2.5 dimethylformamide (3.7 g, 12.6 mmole) and hexamethylphosphoramide (5 ml) in acetonitrile (100 ml) was stirred magnetically at 0° C. for 5 minutes. A solution of (E)-3-phenyl-2-propenoyl chloride (4.7 g, 20 mmole) in acetonitrile (25 ml) was rapidly added to the stirred reaction mixture and stirring was continued for 5 minutes. The reaction mixture was quenched with 6N hydrochloric acid and poured into water (500 ml). This aqueous mixture was extracted with ether (3×200 ml). The ether extracts were combined, washed with brine (3×100 ml), dried over magnesium sulfate and filtered. The filtrate was evaporated in vacuo leaving the title compound as a yellow solid. This yellow solid was chromatographed on a silica gel column (200 g). Elution with methylene chloride (500 ml) provided a forerun which was discarded. Continued elution with the same eluant (550 ml) gave the title compound as a light yellow solid (2.2 g, 54%), melting at 92°-94° C.: pmr (CDCl 3 )δ6.6 (H, dd), 9.72 (H, d).
Step B. Preparation of (E)-6-[2-(3,4-Dichlorophenyl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
By substituting an equimolar amount of (E)-3,4-dichlorocinnamaldehyde for (E)-2,4-dichloro-6-phenylmethoxycinnamaldehyde in Step C of Example 1 and following the procedure for Steps C through F, there was obtained a corresponding amount of the title compound.
trans isomer: mp 116°-118° C.
Analysis Calc. for C 13 H 12 Cl 2 O 3 . Calc.: C, 54.37; H, 4.21. Found: C, 54.60; H, 3.96.
EXAMPLE 11
Preparation of Trans-(E)-6-[2-(2,4-dichloro-6-phenoxyphenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
Step A. Preparation of 2,4-Dichloro-6-phenoxybenzaldehyde
Sodium methoxide (0.54 g, 10 mmole) was added to a stirred solution containing 4,6-dichlorosalicylaldehyde (1.9 g, 10 mmole) in methanol (15 ml). After stirring the reaction solution for 15 minutes at 25° C., diphenyliodonium chloride (3.16 g, 10 mmole) was added in one portion. The resulting reaction mixture was refluxed for 30 hours and then concentrated in vacuo. The residue was suspended in water (100 ml) and the mixture was extracted with ether (3×50 ml). The ether extracts were combined, washed with brine (2×50 ml), dried over magnesium sulfate and filtered. The filtrate was evaporated in vacuo leaving the title compound as a brown oil which solidified upon trituration with hexane. This solid was recrystallized from hexane to give pale yellow needles (0.8 g, 30%) which melted at 99°-101° C., pmr (CDCl 3 ) δ6.68 (H, d), 7.28 (6H, m), 10.58 (H, s).
Analysis Calc. for C 13 H 8 Cl 2 O 2 . Calc.: C, 58.45; H, 3.02. Found: C, 58.26; H, 3.01.
Step B. Preparation of Trans-(E)-6-[2-(2,4-dichloro-6-phenoxyphenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
By substituting an equimolar amount of 2,4-dichloro-6-phenoxybenzaldehyde in place of 2,4-dichloro-6-phenylmethoxybenzaldehyde in Step B of Example 1 and following the procedure for Steps B through F, there was obtained a corresponding amount of the title compound: trans isomer, mp 124°-126° C.
Analysis Calc. for C 19 H 16 Cl 2 O 4 . Calc.: C, 60.17; H, 4.25. Found: C, 60.33; H, 4.30.
EXAMPLE 12
By Substituting an equimolar amount of the following substituted diphenyliodonium chlorides for diphenyliodonium chloride in Step A of Example 11 and following essentially the procedure of Steps A and B in Example 11, there was obtained a corresponding amount of the following end product.
______________________________________Substituents onDiphenyliodoniumchloride End Product______________________________________4,4'difluoro trans-(E)-6-{2-[2,4-dichloro- 6-(4-fluorophenoxy)phenyl]- ethenyl}-3,4,5,6-tetrahydro-4- hydroxy-2H--pyran-2-one2,2'-methoxy trans-(E)-6-{2-[2,4-dichloro- 6-(2-methoxyphenoxy)phenyl]- ethenyl}-3,4,5,6-tetrahydro-4- hydroxy-2H--pyran-2-one4,4'-dimethyl trans-(E)-6-{2-[2,4-dichloro- 6-(4-methylphenoxy)phenyl]- ethenyl}-3,4,5,6-tetrahydro-4- hydroxy-2H--pyran-2-one______________________________________
EXAMPLE 13
Resolution of the Optical Isomers of (±)Trans-(E)-6-[2-(2,4-dichlorophenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
Step A. Preparation and Separation of Diastereomeric Amides (Diastereomers A and B)
A solution of (±)-trans-(E)-6-[2-(2,4-dichlorophenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (2.87 g, 10 mmole) in d-(+)-α-methylbenzylamine (15 ml) was stirred for 18 hours at 25° C. and then poured into water (100 ml). This aqueous mixture was acidified with 6N hydrochloric acid and then extracted with ether (3×100 ml). The ether extracts were combined, washed with brine (4×75 ml), dried over magnesium sulfate and filtered. Evaporation of the filtrate in vacuo gave the intermediate diastereomeric amides as a tan viscous oil (4.1 g).
The tan viscous oil (3.1 g, 7.6 mmole) was chromatographed on a silica gel column (200 g). Elution with acetone-methylene chloride (1:4, v:v; 1200 ml) gave a forerun which was discarded. Continued elution with the same eluant (1000 ml) gave the diastereomeric amides as a viscous oil (3.0 g).
The diastereomeric amides were separated by chromatography on a Waters Prep LC500. The separation was accomplished by using two prep PAK-500 silica cartridges in series and eluting with acetone-methylene chloride (1:4, v:v). Using the shave-recycle technique, diastereomer A (1.36 g) and diastereomer B (1.20 g) were obtained.
Recrystallization of diastereomer A from n-butyl chloride gave colorless clusters (1.0 g) which melted at 106°-108° C.: pmr (CDCl 3 ) δ1.47 (3H, d), 2.33 (2H, d), 4.30 (H, m), 5.17 (H, q), 7.33 (8H, m).
Analysis Calc. for C 21 H 23 Cl 2 NO 3 . Calc.: C, 61.77; H, 5.68; N, 3.43. Found: C, 61.78; H, 5.78; N, 3.50.
Recrystallization of diastereomer B from n-butyl chloride-petroleum ether gave a pale yellow solid which melted at 55°-60° C.: pmr (CDCl 3 ) δ1.47 (3H, d), 2.33 (2H, d), 4,30 (H, m), 5.17 (H, q), 7.33 (8H, m).
Analysis Calc. for C 21 H 23 Cl 2 NO 3 . Calc.: C, 61.77; H, 5.68; N, 3.43. Found: C, 61.41; H, 5.87; N, 3.30.
Step B: Preparation of (+)-Trans-(E)-6-[2-(2,4-dichlorophenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
Diastereomer A (0.74 g, 1.8 mmole) of Step A was dissolved in 95% ethanol (25 ml) containing 1N sodium hydroxide (3.6 ml, 3.6 mmole) and the solution was refluxed for 54 hours. The solvent was removed in vacuo and the residue was suspended in water (100 ml) and acidified with 6N hydrochloric acid. This aqueous mixture was extracted with ether (3×75 ml). The ether extracts were combined, washed with brine (2×50 ml), dried over magnesium sulfate and filtered. The filtrate was evaporated in vacuo leaving the intermediate acid as a yellow oil (0.54 g).
A solution of the yellow oil in toluene (150 ml) was refluxed through a soxhlet containing molecular sieves (3 Å) for 5 hours. The solution was evaporated in vacuo leaving the title compound as a yellow solid. The title compound was purified by recrystallization from ether and then n-butyl chloride to give white needles (0.11 g, 20%) melting at 114°-115° C., pmr (CDCl 3 ) δ2.03 (2H, m), 2.73 (2H, m), 4.46 (H, m), 5.41 (H, m), 6.19 (H, dd) 7.01 (H, d), 7.14-7.50 (3H, m).
Analysis Calc. for C 13 H 12 Cl 2 O 3 . Calc.: C, 54.37; H, 4.21. Found: C, 54.51; H, 4.32.
[α] D 25 =+5.9° (c 0.425; chloroform)
Step C. Preparation of (-)Trans-(E)-6-[2-(2,4-Dichlorophenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
Diastereomer B (1.1 g, 2.7 mmole) of Step A was dissolved in 95% ethanol (25 ml) containing 1N sodium hydroxide (5.4 ml, 5.4 mmole) and the solution was refluxed for 18 hours. The ethanol was removed in vacuo and the residue was suspended in water (100 ml) and acidified with 6N hydrochloric acid. This aqueous mixture was extracted with ether (2×100 ml). The ether extracts were combined, washed with brine (3×50 ml), dried over magnesium sulfate and filtered. The filtrate was evaporated in vacuo leaving the intermediate acid as a yellow oil (0.85 g).
A solution of the yellow oil in toluene (150 ml) was refluxed through a soxhlet containing molecular sieves (3 Å) for 5 hours. The solution was evaporated in vacuo leaving the title compound as a yellow solid. The title compound was recrystallized twice from n-butyl chloride to give white needles (0.34 g, 44%) melting at 114°-115° C.: pmr (CDCl 3 ) δ2.03 (2H, m), 2.73 (2H, m), 4.46 (H, m), 5.41 (H, m), 6.19 (H, dd), 7.01 (H, d), 7.14-7.50 (3H, m).
Analysis Calc. for C 13 H 12 Cl 2 O 3 . Calc.: C, 54.37; H, 4.21. Found: C, 54.31; H, 4.26.
[α] D 25 =-6.6° (c 0.555; chloroform)
EXAMPLE 14
Resolution of the Optical Isomers of (±)Trans-6-[2-2,4-dichloro-6-phenylmethoxyphenyl)ethyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
Step A. Preparation and Separation of Diastereomeric Amides (Diastereomers A and B)
By substituting an equimolar amount of (±)trans-6-[2-(2,4-dichloro-6-phenylmethoxyphenyl)ethyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one for (±)trans-(E)-6-[2-(2,4-dichlorophenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one and replacing d-(+)-α-methylbenzylamine with the l-(-)-isomer in Step A of Example 13 and following the procedure described in Step A of Example 13, there was obtained a corresponding amount of the diastereomeric amides:
Diastereomer A:
mp 177°-179° C.; pmr (CDCl 3 ) δ1.45 (3H, d), 2.22 (2H, d), 2.83 (2H, m), 3.74 (H, m), 4.13 (H, m), 5.04 (2H, s), 6.86 (H, d), 7.05 (H, d), 7.33 (5H, s), 7.82 (5H, s).
Analysis Calc. for C 28 H 31 Cl 2 NO 4 . Calc.: C, 65.11; H, 6.05; N, 2.71. Found: C, 65.28; H, 6.34; N, 2.95.
Diastereomer B:
mp 130°-132° C.; pmr (CDCl 3 ) δ1.45 (3H, d), 2.22 (2H, d), 2.83 (2H, m), 3.74 (H, m), 4.13 (H, m), 5.04 (2H, s), 6.86 (H,d), 7.05 (H, d), 7.33 (5H, s), 7.82 (5H, s).
Analysis Calc. for C 28 H 31 Cl 2 NO 4 . Calc.: C, 65.11; H, 6.05; N, 2.71. Found: C, 65.24; H, 6.27; N, 2.88.
Step B. Preparation of (+)-Trans-6-[2-(2,4-dichloro-6-phenylmethoxyphenyl)ethyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2one. 0.1 n-Butyl Chloride Solvate
By substituting an equimolar amount of diastereomer A from the preceeding step for diastereomer A in Step B of Example 13 and following the procedure described therein, there was obtained a corresponding amount of the title compound, mp 108°-112° C.; pmr (CDCl 3 ) δ1.91 (4H, m), 2.61 (2H, m), 2.93 (2H, m), 4.30 (H, m), 4.70 (H, m), 5.06 (2H, s), 6.33 (H, d), 7.02 (H, d), 7.43 (5H, s).
Analysis Calc. for C 20 H 20 Cl 2 O 4 .0.1C 4 H 9 Cl. Calc.: C, 60.56; H, 5.21. Found: C, 60.93; H, 5.73.
[α] D 25 =+16.6° (c, 0.1; chloroform).
Step C. Preparation of (-)-Trans-6-[2-(2,4-dichloro-6-phenylmethoxyphenyl)ethyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one.0.1 n-Butyl Chloride Solvate
By substituting an equimolar amount of diastereomer B from Step A above for diastereomer B in Step C of Example 13 and following the procedure described therein, there was obtained a corresponding amount of the title compound, mp 104°-111° C.; pmr (CDCl 3 ) δ1.91 (4H, m), 2.61 (2H, m), 2.93 (2H, m), 4.30 (H, m), 4.70 (H, m), 5.06 (2H, s), 6.33 (H, d) 7.02 (H, d), 7.43 (5H, s).
Analysis Calc. for C 20 H 20 Cl 2 O 4 .0.1 C 4 H 9 Cl. Calc.: C, 60.56; H, 5.21. Found: C, 60.62; H, 5.46.
[α] D 25 =-17.7° (c, 0.1; chloroform).
EXAMPLE 15
Preparation of (E)-6-[2-(2,6-Dichlorophenyl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-4-methyl-2H-pyran-2-one
Step A: Preparation of 6-(2,4-Dichlorophenyl)-4-hydroxy-5-hexene-2-one
2-Acetoxypropene (3.3 ml, 30 mmole) and tri-n-butyltin methoxide (5.7 g, 24 mmole) were combined and stirred at 60°-70° C. under N 2 for 1 hour then placed under vacuum for an additional 30 minutes. 3-(2,4-Dichlorophenyl)propenal (4 g, 20 mmole) was added and the reaction mixture was stirred at 70° C. under N 2 for 4 hours. The clear reaction mixture was then cooled, treated with malonic acid (1 g, 10 mmole) in ether (20 ml) and refluxed for 30 minutes. After cooling to -20° C., the reaction mixture was filtered and the precipitate was washed with ether (4×10 ml). The ethereal solutions were combined, evaporated and the residual oil was chromatographed on a 60 mm column with 15 cm of silica gel (230-400 mesh). Elution with chloroform-methanol (99:1, v:v; 2.0 L) provided the title compound as a thick yellow oil (4.2 g, 81%), pmr (CDCl 3 ) 2.2 (3H, s), 2.73 (2H, d), 4.73 (H, m), 6.10 (H, dd).
Analysis Calc. for C 12 H 12 Cl 2 O 2 . Calc.: C, 55.62; H, 4.67. Found: C, 55.55; H, 4.72.
Step B. Preparation of 6-(2,4-Dichlorophenyl)-2-oxo-5-hexene-4-yl 2-Bromoacetate
2-Bromoacetyl bromide (1.1 ml, 13.2 mmole) was added dropwise to a stirred solution of 6-(2,4-dichlorophenyl)-4-hydroxy-5-hexene-2-one (3.4 g, 13.1 mmole) and pyridine (1.07 ml, 13.2 mmole) in ether (100 ml) at 0° C. The ice bath was removed and the reaction mixture was stirred at 20° C. for 2 hours and then diluted with H 2 O (100 ml). The organic layer was separated and washed with 1N HCl (100 ml), H 2 O (2×100 ml) and brine, dried over MgSO 4 , filtered and evaporated. The residual oil was chromatographed on a 60 mm column with 15 cm of silica gel (230-400 mesh) Elution with methylene chloride-acetone (99:1; v:v; 1.9 L) provided the title compound (2.8 g, 56%); pmr (CDCl 3 ) δ2.2 (3H, s), 2.92 (2H, t), 3.85 (2H, s), 5.9 (H, m), 6.15 (H, m) 6.95-7.5 (4H, m).
Step C. Preparation of (E)-6-[2-(2,5-Dichlorophenyl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-4-methyl-2H-pyran-2-one
A solution of 6-(2,4-dichlorophenyl)-2-oxo-5-hexene-4-yl 2-bromoacetate (2.8 g, 7.4 mmole) in dry THF (50 ml) was added dropwise to a vigorously stirred slurry of activated zinc dust (720 mg, 11.1 mmole), cuprous bromide (60 mg, 0.4 mmole), diethylaluminum chloride (25% solution in toluene; 3.2 ml, 8 mmole) and dry THF (50 ml) under N 2 at 20° C. Stirring was continued for 5 hours before quenching with pyridine (8 ml) followed by addition of H 2 O (500 ml) and ether extraction (3×150 ml). The combined ether extracts were washed with 1N HCL (2×50 ml), H 2 O (2×250 ml) and brine, then dried (MgSO 4 ), filtered and evaporated in vacuo leaving a sticky, pale yellow solid (1.8 g) which is a mixture of cis and trans isomers of the title compound. This crude product was digested once with ether (40 ml) and then crystallized from n-butyl chloride (25 ml) to provide the trans isomer of the title compound as tiny, colorless crystals (550 mg), mp 136°-138° C.
Analysis Calc. for C 14 H 14 Cl 2 O 3 . Calc.: C, 55.83; H, 4.69. Found: C, 56.07; H, 4.66.
The filtrates from digestion and crystallization vida supra were combined, evaporated and chromatographed using a Waters Prep LC500. The separation was accomplished by using two prep PAK 500/silica cartridges in series and eluting with methylene chloride-acetone (15:1, v:v). By using the shave-recycle technique, the cis (220 mg) and the trans (230 mg) isomers of the title compound were separated. The cis isomer of the title compound was crystallized from n-butyl chloride-hexane (2:1, v:v) to give 120 mg of solid, mp 135°-137° C.
Analysis Calc. for C 14 H 14 Cl 2 O 3 . Calc.: C, 55.83; H, 4.69. Found: C, 55.46; H, 4.71.
The epimeric alcohols are readily distinguished by analytical TLC (fluorescent silica gel (40 Å), 1×3 in, MK6F, Whatman) and elution with methylene chloride-acetone (9:1; v:v:cis alcohol, R f 0.25; trans alcohol, R f 0.30.
EXAMPLE 16
Alternate Route to (E)-6-[2-(2,6-Dichlorophenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-4-methyl-2H-pyran-2-one
Step A. Preparation of 6-(2,4-Dichlorophenyl)-2-oxo-5-hexene-4-yl Acetate
Acetyl chloride (1.2 ml, 16.5 mmole) was added dropwise to a stirred solution of 6-(2,4-dichlorophenyl)-4-hydroxy-5-hexene-2-one (3.9 g, 15 mmole) in pyridine (60 ml) at 0° C. The ice bath was removed, and the reaction mixture was stirred at 20° C. for 2 hours and then diluted with ether (300 ml). The ether solution was washed with 1N HCl (3×300 ml) and saturated NaHCO 3 , dried over MgSO 4 , filtered and evaporated. The residual pale amber oil (4.1 g) was chromatographed on a 50 mm column with 15 cm of silica gel (230-400 mesh). Elution with methylene chloride (2 L) provided the title compound as a pale yellow oil (3.95 g, 87%): pmr (CDCl 3 ) δ2.03 (3H, s), 2.17 (3H, s), 2.83 (2H, dd).
Analysis Calc. for C 14 H 14 Cl 2 O 3 . Calc.: C, 55.83; H, 4.69. Found: C, 55.82; H, 4.76.
Step B. Preparation of Ethyl 5-Acetoxy-7-(2,4-dichlorophenyl)-3-hydroxy-3-methyl-6-heptenoate
A solution of 6-(2,4-dichlorophenyl)-2-oxo-5-hexene-4-yl acetate (1.3 g, 4.3 mmole) and ethyl bromoacetate (0.47 ml, 4.2 mmole) in dry THF (10 ml) was added dropwise to a vigorously stirred slurry of activated zinc dust (490 mg, 7.5 mmole), cuprous bromide (29 mg, 0.2 mmole), diethylaluminum chloride (25% solution in toluene; 1.72 ml, 4.3 mmole) and dry THF (5 ml) under N 2 at 20° C. Stirring was continued for 5 hours before quenching with pyridine (3.5 ml). After the addition of water (50 ml) the mixture was extracted with ether (3×80 ml). The combined ether extracts were washed with 1N HCl (2×25 ml), H 2 O (2×50 ml) and brine, then dried (MgSO 4 ), filtered and evaporated leaving the crude title compound as a pale yellow oil (1.2 g); pmr (CDCl 3 ) δ1.28 (3H, t), 1.33 (3H, t), 2.10 (3H, s).
Step C. Preparation of (E)-6-[2-(2,6-Dichlorophenyl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-4-methyl-2H-pyran-2-one
Ethyl 5-acetoxy-7-(2,4-dichlorophenyl)-3-hydroxy-3-methyl-6-heptenoate (1.2 g, 3.2 mmole) was stirred with 1N NaOH (6.4 ml, 6.4 mmole) at 50° C. for 1 hour. The aqueous solution was diluted with H 2 O (50 ml) and washed with ether (2×50 ml). The aqueous layer was acidified with 12N HCl and extracted with ether (2×50 ml). The combined organic extracts were washed with brine, dried over MgSO 4 , filtered and evaporated leaving the crude diol acid which was lactonized by refluxing in toluene (75 ml) under a Soxhlet extractor filled with 3 Å sieves for 3 hours. The toluene was evaporated and the residue was chromatographed on a 50 mm column with 15 cm of silica gel (230-400 mesh). Elution with chloroform-methanol (19:1; v:v; 400 ml) provided (120 mg, 12%) of the title compound as a mixture of cis (46%) and trans (54%) isomers as determined by HPLC.
EXAMPLE 17
Preparation of (E)-6-[2-(2'-methoxy-[1,1'-biphenyl]-2-yl)ethenyl]-3,4,5,6-tetrahydro-4hydroxy-2H-pyran-2-one
Step A. Preparation of 2-(2'-Methoxy-[1,1'-biphenyl]-2-yl)-4,4-dimethyl-2-oxazoline
2-Methoxyphenylmagnesium bromide, prepared from 2-bromoanisole (22.4 g, 120 mmol) and magnesium (2.9 g, 120 mmol), in dry THF (75 ml) was added dropwise to a stirred solution of 2-(2-methoxyphenyl)-4,4-dimethyl-2-oxazoline (20.4 g, 100 mmol) in dry THF (150 ml) under N 2 at 20° C. Stirring of the solution was continued for 20 hours and then the reaction mixture was quenched by the addition of saturated ammonium chloride solution. The resulting mixture was extracted with ether (2×500 ml), dried over MgSO 4 , filtered and evaporated. The residue was chromatographed on silica gel (ethyl acetate-hexane) to provide title compound as colorless crystals (25.3 g, 90%), mp 129°-131° C.
Step B. Preparation of 2'-Methoxy-[1,1'-biphenyl]-2-carboxylic acid
2-(2'-Methoxy-[1,1'-biphenyl]-2-yl)-4,4-dimethyl-2-oxazoline (25 g, 90 mmol) was dissolved in 4.5N HCl (1.5L) and heated at reflux for 20 hours. After cooling, the heterogeneous mixture was extracted with ether (3×200 ml). The etheral extracts were combined and washed with H 2 O and brine, dried over MgSO 4 , filtered and then evaporated to provide the title compound (15.4 g, 75%), mp 196°-197° C., as a colorless solid.
Step C. Preparation of 2'-Methoxy-[1,1'-biphenyl]-2-carbonyl Chloride
2'-Methoxy-[1,1'-biphenyl]-2-carboxylic acid (32 g., 100 mmole) was dissolved in thionyl chloride (40 ml) and the solution was refluxed for 3 hours. The solution was evaporated to provide the title compound.
Step D. Preparation of (E)-6-[2-(2'-Methoxy-[1,1'-biphenyl]-2-yl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
Starting with 2'-methoxy-[1,1'-biphenyl]-2-carbonyl chloride in place of 2,3-dichlorobenzoyl chloride, the title compound was prepared following the procedures of Examples 6, Step A, and then Example 1, Steps C through F.
EXAMPLE 18
Preparation of (E)-6-[2-(4'-chloro-[1,1'-biphenyl]-2-yl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
Starting with 4-chlorophenylmagnesium bromide, in place of the 2-methoxyphenylmagnesium bromide, the title compound was prepared following the procedure of Example 17, Steps A through D.
EXAMPLE 19
Preparation of (E)-6-[2-(4'-Fluoro-[1,1'-biphenyl]-2-yl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
Starting with 4-fluorophenylmagnesium bromide, in place of the 2-methoxyphenylmagnesium bromide, the title compound was prepared following the procedure of Example 17, Steps A through D.
EXAMPLE 20
Preparation of (E)-6-[2-(4'-methyl-[1,1'-biphenyl]-2-yl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
Starting with 4-methylphenylmagnesium bromide, in place of the 2-methoxyphenylmagnesium bromide, the title compound was prepared following the procedure of Example 17, Steps A through D.
EXAMPLE 21
Preparation of 6-[2-(2,4-Dichloro-6-hydroxyphenyl)ethyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
Step A. Preparation of 6-{2-[2,4-Dichloro-6-(2-methoxyethoxymethoxy)phenyl]ethyl}-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
Starting with (E)-6-{2-[2,4-Dichloro-6-(2-methoxyethoxymethoxy)phenyl]ethenyl}-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one and following the procedure of Example 8, the title compound was obtaind as a viscous golden oil: pmr (CDCl 3 ) δ2.63 (2H, d), 3.36 (3H, s), 3.55 (2H, m), 3.8 (2H m), 4.35 (H, m), 4.73 (H, m), 5.27 (2H, s), 7.6 (2H, dd).
Step B. Preparation of 6-{2-(2,4-Dichloro-6-hydroxyphenyl)-ethyl}-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
Zinc bromide (2.4 g, 10 mmole) was added to a solution of 6-{2-[2,4-dichloro-6-(2-methoxyethoxymethoxy)phenyl]ethyl}-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (780 mg, 2 mmole) in methylene chloride (12 ml). The resulting mixture was stirred at 20° C. for 2 hours, then quenched with saturated sodium bicarbonate solution (50 ml) and diluted with ether (200 ml). The ethereal layer was washed with brine, dried over MgSO 4 , filtered and evaporated. The residue was chromatographed on a 50 mm low-pressure column with 6 inches of silica gel (230-400 mesh). The column was eluted with 470 ml of methylene chloride-acetone (4:1, v:v). The next 330 ml provided the title compound as a golden glass (100 mg., 16%): pmr (CDCl 3 ) δ2.62 (2H, d), 4.29 (H, m), 4.78 (H, m), 6.87 (2H, s).
EXAMPLE 22
Preparation of 6-{2-[2,4-Dichloro-6-(4-trifluoromethylphenylmethoxy)phenyl]ethyl}-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
By following the procedure of Example 1, step A, but substituting equimolar amounts of 6-{2-(2,4-dichloro-6-hydroxyphenyl)ethyl}-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one and 4-trifluoromethylbenzyl bromide for the 4,6-dichlorosalicylaldehyde and benzyl bromide used therein, the title compound is obtained, m.p. 104°-105° C.
EXAMPLE 23
Preparation of 6-[2-(2-acetoxy-4,6-dichlorophenyl)ethyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
Acetyl chloride (0.08 ml, 1.05 mmole) was added dropwise to a stirred solution of 6-[2-(2,4-dichloro-6-hydroxyphenyl)ethyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (300 mg, 1 mmole) and pyridine (0.09 ml, 1.05 mmole) in ether (10 ml) at 0° C. The ice bath was removed and the reaction mixture was stirred at 20° C. for 1 hour and then diluted with H 2 O (10 ml). The organic layer was separated and washed with 1N HCl (10 ml), H 2 O (2×10 ml) and brine, dried over MgSO 4 , filtered and evaporated to provide the title compound.
EXAMPLE 24
Preparation of 6-[2-(2-Benzoyloxy-4,6-dichlorophenyl)ethyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
By following the procedure of Example 23, but substituting an equivalent amount of benzoyl chloride for the acetyl chloride used therein, the title compound is obtained.
EXAMPLE 25
Preparation of (E)-Trans-6-[2-(3-trifluoromethylphenyl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
By substituting an equimolar amount of 3-trifluoromethylbenzaldehyde for 2,4-dichloro-6-phenylmethoxybenzaldehyde in step B of Example 1 and following Steps B through F, there is obtained a corresponding amount of the title compound.
EXAMPLE 26
Preparation of Trans-6-(2-chlorophenylmethyl)-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
By substituting an equimolar amount of o-chlorophenylacetaldehyde for 2,4-dichloro-6-phenylmethoxybenzaldehyde in step C of Example 1 and following Steps C through F there is obtained a corresponding amount of the title compound.
EXAMPLE 27
Preparation of (E)-6-[2-(2,4-dichloro-6-methoxyphenylethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
The procedure of Example 1 is followed using an equivalent amount of methyl iodide in place of benzyl bromide in Step A. The compound named above is obtained.
EXAMPLE 28
Preparation of (E)-6-[2-(2,4-dichloro-6-cyclopropylmethoxyphenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
The procedure of Example 1 is followed using an equivalent amount of cyclopropylmethyl iodide in place of benzyl bromide in Step A. The above named compound is obtained.
EXAMPLE 29
Trans-6-(3-phenylpropyl)-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
Step A. Preparation of 4-Phenylbutyronitrile
A mixture of 1-bromo-4-phenylbutane (58.8 g, 0.24 mole) and sodium cyanide (25 g, 0.5 mole) in ethanol (300 ml)-water (100 ml) is heated at reflux with stirring for 5 hours. The resulting reaction mixture is concentrated in vacuo and extracted with ether. The ethereal extract is filtered and evaporated at reduced pressure to afford the title compound which is purified by distillation.
Step B. Preparation of 4-Phenyl-1-butanal
To a stirred suspension of 4-phenylbutyronitrile (21.7 g, 0.12 mole) in ether (400 ml) at 78° C. is added 85 ml. of 25.3% diisobutylaluminum hydride in toluene over a period of 1 hour. After an additional 1 hour, the dry ice-acetone bath is removed and the reaction mixture is stirred at ambient temperature for 3 hours. The reaction mixture is added slowly to 5% aqueous sulfuric acid and then is extracted with several portions of ether. The ether extracts are combined, washed with water and saturated aqueous sodium chloride solution and dried over magnesium sulfate. After removal of the ether, the residual yellow oil is distilled in vacuo to give an oil.
Step C. Trans-6-(3-phenylpropyl)-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
This product is prepared from 4-phenyl-1-butanal in a manner similar to Steps C, D and E in Example 1. The product is purified by column chromatography and high pressure liquid chromatography to give the title compound.
EXAMPLE 30
Preparation of 6-{2-[6-[(4-acetoxyphenyl)methoxy]-2,4-dichlorophenyl]ethyl}-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
By following the procedure of Example 1, Step A, but substituting equimolar amounts of 6-[2-(2,4-dichloro-6-hydroxyphenyl)ethyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one and 4-(bromomethyl)phenol acetate for the 4,6-dichlorosalicylaldehyde and benzyl bromide used therein, the title compound is obtained.
EXAMPLE 31
Preparation of 6-{2-[2,4-Dichloro-6-(4-hydroxyphenylmethoxyphenyl]ethyl}-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
By following the procedure of Example 16, Step C, but substituting an equimolar amount of 6-{2-[6-(4-acetoxyphenylmethoxy)-2,4-dichlorophenyl]ethyl}-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one for the ethyl 5-acetoxy-7-(2,4-dichlorophenyl)-3-hydroxy-3-methyl-6-heptenoate used therein, the title compound is obtained.
EXAMPLE 32
Preparation of (E)-trans-6-{2-[3,5-Dichloro-4'-fluoro-2-(1,1'-biphenyl)yl]ethenyl}-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
Step A. Preparation of 2,4-Dichloro-6-methoxybenzaldehyde
By substituting an equimolar amount of methyl iodide for benzyl bromide in Step A of Example 1 there was obtained a corresponding amount of the title compound as a white powder, mp 110°-111° C.
Step B. Preparation of N-(2-Hydroxy-1,1-dimethylethyl)-2,4-dichloro-6-methoxybenzamide
A suspension of 2,4-dichloro-6-methoxybenzaldehyde (3 g, 15 mmol) and N-bromosuccinimide (3.6 g, 20 mmol) in carbon tetrachloride (30 ml) was illuminated with a 150 W flood lamp under nitrogen with vigorous stirring on a steam bath for seven minutes. The cloudy mixture was cooled to 0° C., diluted with methylene chloride (30 ml) and treated dropwise with a solution of 2-amino-2-methylpropanol (3 ml, 30 mmol) in methylene chloride (30 ml). The ice bath was removed and the mixture was stirred at 20° C. for twenty hours.
The reaction mixture was filtered and the collected solids were washed with additional methylene chloride (50 ml). The clear filtrates were combined and washed with H 2 O (100 ml), 5% HCl (100 ml), 5% NaOH (100 ml), H 2 O (100 ml) and brine, then dried (MgSO 4 ), filtered and evaporated in vacuo to provide the title compound as a white powder (3.6 g, 82%), mp 130°-132° C. Crystallization from hexane-toluene (10:8, v:v) provided an analytical sample of title compound, mp 131°-132° C.
Analysis Calc. for C 12 H 15 Cl 2 NO 3 . Calc: C, 49.33; H, 5.18; N, 4.79. Found: C, 49.51; H, 5.27; N, 4.62.
Step C. Preparation of 2-(2,4-Dichloro-6-methoxyphenyl)-4,4-dimethyl-2-oxazoline
N-(2-Hydroxy-1,1-dimethylethyl)-2,4-dichloro-6-methoxybenzamide (5.5 g, 18.8 mmol) was treated dropwise with thionyl chloride (5.5 ml) and stirred magnetically at 20° C. for 30 min. Dry ether (100 ml) was added, the mixture was stirred for an additional one hour and the oxazoline hydrochloride precipitate was collected by filtration. The salt was neutralized with 20% sodium hydroxide to afford an alkaline mixture which was extracted with ether. The ethereal extract was dried (MgSO 4 ) and concentrated to give an oil (3.6 g, 70%), which crystallized on standing, mp 47°-50° C.
Analysis for C 12 H 13 Cl 2 NO 2 . Calc: C, 52.57; H, 4.78; N, 5.11. Found: C, 52.60; H, 4.98; N, 4.99.
Step D. Preparation of 2-(3,5-Dichloro-4'-fluoro-2-[1,1'-biphenyl]yl)-4,4-dimethyl-2-oxazoline
By substituting equimolar amounts of 2-(2,4-dichloro-6-methoxyphenyl)-4,4-dimethyl-2-oxazoline and 4-fluorophenylmagnesium bromide for 2-(2-methoxyphenyl)-4,4-dimethyl-2-oxazoline and 2-methoxyphenylmagnesium bromide, the title compound was prepared following the procedure of Example 17, Step A, (85%), mp 93°-95° C.
Analysis for C 17 H 14 Cl 2 FNO. Calc: C, 60.37; H, 4.17; N, 4.14. Found: C, 60.72; H, 4.17; N, 3.89.
Step E. Preparation of 2-(3,5-Dichloro-4'-fluoro-2-[1,1'-biphenyl]yl)-3,4,4-trimethyl-2-oxazolium iodide
A solution of 2-(3,5-dichloro-4'-fluoro-2-[1,1'-biphenyl]yl)-4,4-dimethyl-2-oxazoline (4.6 g, 13.6 mmol) and methyl iodide (7 ml) in nitromethane (30 ml) was stirred on a steam bath for sixteen hours. The cooled reaction mixture was diluted with dry ether (200 ml) and, after cooling in an ice-bath, the crystalline product was collected to give 6 g (92%) of the title compound, mp 214°-216° C. dec. Crystallization from acetonitrile-ether (1:3, v:v) provided an analytical sample of the title compound, mp 218°-219.5° C. dec.
Analysis for C 18 H 17 Cl 2 FINO. Calc: C, 45.03; H, 3.57; N, 2.92. Found: C, 44.94; H, 3.47; N, 2.83.
Step F. Preparation of 3,5-Dichloro-4'-fluoro-[1,1'-biphenyl]-2-carboxaldehyde
A vigorously stirred suspension of 2-(3,5-dichloro-4'-fluoro-2-[1,1'-biphenyl]yl)-3,4,4-trimethyl-2-oxazolium iodide (5.9 g, 12.3 mmol) in ethanol (50 ml) was treated portionwise with sodium borohydride (550 mg, 18 mmol). After stirring for two hours at ambient temperature the clear solution was diluted with 3N hydrochloric acid (100 ml) and stirred on a steam bath for two hours. The reaction mixture was then cooled, diluted with H 2 O (200 ml) and extracted with ether (300 ml). The ether extract was washed with H 2 O (2×200 ml) and brine, then dried (MgSO 4 ), filtered and evaporated in vacuo to provide 2.72 g (82%) of the title compound, mp 66°-68° C. Crystallization from petroleum ether provided an analytical sample of the title compound, mp 73°-74° C.
Analysis for C 13 H 7 Cl 2 FO. Calc: C, 58.02; H, 2.62. Found: C, 58.15; H, 2.52.
Step G. Preparation of (E)-trans-6-[2-(3,5-dichloro-4'-fluoro-[1,1'-biphenyl]-2-yl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
By substituting an equimolar amount of 3,5-dichloro-4'-fluoro-[1,1'-biphenyl]-2-carboxaldehyde in place of 2,4-dichloro-6-phenylmethoxybenzaldehyde in the alternate to alternate Step B, of Example 1 and then following the procedures of Step B through F, there was obtained a corresponding amount of the title compound, mp 121°-122° C.
Analysis for C 19 H 15 Cl 2 FO 3 . Calc: C, 59.86; H, 3.97. Found: C, 59.70; H, 3.97.
The cis isomer of the title compound was obtained in comparable yield after crystallization from n-butyl chloride, mp 107°-108° C.
EXAMPLE 33
Starting with 2-(2,4-Dichloro-6-methoxyphenyl)-4,4-dimethyl-2-oxazoline but substituting equimolar amounts of the following Grignard reagents in place of 4-fluorophenylmagnesium bromide in Step D of Example 32 and following the procedures of Steps D through G there was obtained a corresponding amount of the appropriate end product listed below.
__________________________________________________________________________ Grignard mpReagent End Product °C. Calc. Found__________________________________________________________________________phenyl (E)-trans-6-[2-(3,5-di- 113-115° C 62.83 C 62.47 chloro-2-[1,1'-biphenyl]- H 4.44 H 4.64 yl)ethenyl]-3,4,5,6-tetra- hydro-4-hydroxy-2H--pyran- 2-one4-chlorophenyl (E)-trans-6-[2-(3,4',5- 116.5-118° C 57.38 C 57.07 trichloro-2-[1,1'-biphenyl]- H 3.80 H 3.85 yl)ethenyl]-3,4,5,6-tetra- hydro-4-hydroxy-2H--pyran- 2-one__________________________________________________________________________
EXAMPLE 34
Alternate Preparation of 3,5-Dichloro-4'-fluoro-[1,1'-biphenyl]-2-carboxaldehyde
Step A. Preparation of Bis[μ-(Acetato-0:0')bis-(3,5-dichloro-2[(phenylimino)methyl]phenyl-C,N]dipalladium
A mixture of N-[(2,4-Dichlorophenyl)methylene]benzeneamine (2.5 g, 10 mmole) and palladium (II) acetate (2.24 g, 10 mmole) in acetic acid (50 ml) was heated at reflux for one hour with stirring. The turbid solution was filtered and the filtrate was diluted with water (300 ml) to give the title compound as a red solid (3.9 g, 94%). Crystallization from acetic acid-water (7:1, v:v) provided an analytical sample of the title compound, mp 203°-205° C.: pmr (CDCl 3 )δ1.73 (3H, S), 6.50 (H, d, J=1.5 Hz) 6.97 (2H, m), 7.12 (H, d, J=1.5 Hz) 7.33 (3H, m), 8.03 (H, S).
Analysis Calc. for C 30 H 22 Cl 2 N 4 O 4 PD 2 . Calc: C, 43.42; H, 2.67; N, 3.38. Found: C, 43.54; H, 2.59; N, 3.13.
Step B. Preparation of 3,5-Dichloro-4'-fluoro-[1,1'-biphenyl]-2-carboxyldehyde
A solution of bis-[μ-(Acetato-0:0')bis-[3,5-dichloro-2-[(phenylimino)methyl]phenyl-C,N]dipalladium (8.29 g, 10 mmole) and triphenylphosphine (21.0 g, 80 mmole) in dry benzene (150 ml) was stirred for 30 minutes at ambient temperature under N 2 . The 4-fluorophenylmagnesium bromide, prepared from 4-bromofluorobenzene (15.4 g, 88 mmole) and magnesium (1.94 g, 80 mmole) in dry ether (100 ml) under N 2 at ambient temperature, was added to the above solution in one portion. The resulting mixture was stirred for one hour at ambient temperature. After the addition of 6N HCl (50 ml) with stirring for one hour, the mixture was filtered. The filtrate was diluted with ether (300 ml) and washed with brine (2×100 ml). The organic layer was refiltered to remove more yellow solid and the filtrate, washed with brine (2×100 ml), dried over MgSO 4 , filtered and evaporated. The residue was chromatographed on a silica column (1000 g). Elution with ether-hexane (1:39, v:v, 5500 ml) provided a forerun which was discarded. Continued elution with ether-hexane (1:9, v:v, 5700 ml) gave the title compound as a yellow solid (4.5 g, 84%), mp 73°-74° C.: pmr (CDCl 3 )δ7.03-7.40 (5H, m), 7.53 (H, d, J=1.5 Hz), 10.13 (H, S).
EXAMPLE 35
Starting with bis[μ-(Acetato-0:0')bis-[3,5-dichloro-2[(phenylimino)methyl]phenyl-C,N]dipalladium but substituting equal amounts of the following Grignard reagents for 4-fluorophenylmagnesium bromide in Step B of Example 34 and following the procedure of Step B there was obtained a corresponding amount of the appropriate end product listed below.
EXAMPLE 35
__________________________________________________________________________GRIGNARD PRODUCT pmr (δ)__________________________________________________________________________3-methylphenyl 3,5-dichloro-3'-methyl-[1,1'- 2.3 (3H.S), 7.0-7.8 biphenyl]-2-carboxaldehyde (6H,m), 9.8 (H,s)3,5-dimethylphenyl 3,5-dichloro-3',5'-dimethyl- 2.3 (6H,s), 6.7-7.5 [1,1'-biphenyl]-2-carboxaldehyde (5H,m), 10.0 (H,s)4-fluoro-2-methyl 3,5-dichloro-4'-fluoro-2'- 2.0 (3H,s), 6.9-7.5phenyl methyl-[1,1'-biphenyl]-2- (5H,m), 10.1 (H,s) carboxaldehyde3-ethylphenyl 3,5-dichloro-3'-ethyl-[1,1'- 1.4 (3H,t), 2.9 (2H,q), biphenyl]-2-carboxaldehyde 7.2-7.6 (6H,m), 10.0 (H,s)4-fluoro-3-methyl 3,5-dichloro-4'-fluoro- 2.3 (3H,s), 7.0-7.5 (5H,m)phenyl 3'-methyl-[1,1'-biphenyl]- 10.1 (H,s) 2-carboxaldehyde3,4-dichlorophenyl 3,3',4',5-tetrachloro- 7.0-7.6 (5H,m), [1,1'-biphenyl]-2-carboxaldehyde 10.3 (H,s)3,5-dichlorophenyl 3,3',5,5'-tetrachloro- 7.1-7.6 (5H,m), [1,1'-biphenyl]-2-carboxaldehyde 10.3 (H,s)2-methylphenyl 3,5-dichloro-2'-methyl-[1,1'- 2.1 (3H,s), 7-7.6 biphenyl]-2-carboxaldehyde (6H,m), 10.0 (H,s)3-methoxyphenyl 3,5-dichloro-3'-methoxy-[1,1'- 3.9 (3H,s), 6.8-7.6 biphenyl]-2-carboxaldehyde (6H,m), 10.1 (H,s)4-methylphenyl 3,5-dichloro-4'methyl-[1,1'- 2.40 (3H,S), 7.13-7.40 biphenyl]-2-carboxaldehyde (5H,m), 7.50 (H,d, J = 1.5 Hz), 10.06 (H,S)4-methoxyphenyl 3,5-dichloro-4'-methoxy-[1,1'- 3.85 (3H,S), 6.93-7.50 biphenyl]-2-carboxaldehyde (6H,m), 10.03 (H,S)3-fluorophenyl 3,5-dichloro-3'-fluoro-[1,1'- 6.93-7.60 (6H,m), biphenyl]-2-carboxaldehyde 10.16 (H,S)__________________________________________________________________________
EXAMPLE 36
5-chloro-4'-Fluoro-3,3'-dimethyl-[1,1'-biphenyl]-2-carboxaldehyde
Step A: Preparation of N-[4-chloro-2-methyl(phenyl)methylene]-benzeneamine
A mixture of 4-chloro-2-methylbenzaldehyde (3.5 g, 22.6 mmol) and aniline (2.11 g, 22.6 mmol) in toluene (40 ml) was heated at reflux in a Dean-Stark apparatus for 1 hour. The mixture was cooled and evaporated in vacuo to leave an oily residue. The residue was redissolved in ether, washed with 5% sodium bicarbonate solution. The organic phase was separated, dried over MgSO 4 and filtered. The filtrate was concentrated in vacuo to afford an oily residue which was purified by distillation via a Kugelrohr apparatus (oven temperature 160° C., 0.5 mm) to provide the title compound (4.0 g, 7.4 mmol, 77%) as a viscous oil; pmr(CDCl 3 )δ2.5 (3H, s), 6.3˜7.5(7H, m), 7.95(H, d), 8.6(H, s).
Step B: Preparation of 5-chloro-4'-fluoro-3,3'-dimethyl-[1,1'-biphenyl]-2-carboxaldehyde
By substituting an equimolar amount of N-[(4-chloro-2-methylphenyl)methylene]benzeneamine in place of N-[(2,4-dichlorophenyl)methylene]benzeneamine in step A of example 34 and replacing the 4-fluophenylmagnesium bromide with an equimolar amount of 4-fluoro-3-methylphenylmagnesium bromide) in Step B of example 34 and following the procedures described therein, there was obtained a corresponding amount of the title compound; pmr(CDCl 3 )δ 2.30(3H, d), 2.60(3H, s), 7.1 7.3(5H, m), 9.9(H, s).
EXAMPLE 37
3', 4'-Dichloro-3,5-dimethyl-[1,1'-biphenyl]-2-carboxaldehyde
By substituting an equimolar amount of N-[(2,4-dimethylphenyl)methylene]benzeneamine in place of N-[(2,4-dichlorophenyl)methylene]benzeneamine in Step A of Example 24 and replacing the 4-fluorophenylmagnesium bromide with an equimolar amount of 3,4-dichlorophenylmagnesium bromide in Step B of Example 34 and following the procedures described therein, there was obtained a corresponding amount of the title compound, mp 80°-81° C.; pmr(CDCl 3 )δ2.4(3H, s), 2.6(3H, s), 7.0-7.5(5H, m), 10.0(H, s).
Analysis Calc. for C 15 H 12 Cl 2 O: C, 64.54; H, 4.33. Found: C, 64.83; H, 4.45.
EXAMPLE 38
Employing the procedure substantially as described in Example 37, but substituting for the 3,4-dichlorophenylmagnesium bromide used therein, an equimolecular amount of the Grignard reagents listed below there were prepared the corresponding substituted biphenyl-2-carboxaldehydes.
______________________________________GRIG-NARD PRODUCT pmr (δ)______________________________________4-Fluoro-3- 4'-fluoro-3,3',5-trimethyl- 2.4(3H,d), 2.5(3H,s),methyl- [1,1'-biphenyl]-2-carbox- 2.7(3H,s), 7.0-7.3(5H,m),phenyl aldehyde 9.9(1H,s)3,5-di- 3,3',5,5'-tetramethyl-[1,1'- 2.3(9H,m), 2.6(3H,s)methyl- biphenyl]-2-carbox- 6.8-7.0(5H,m) 10.0(1H,s)phenyl aldehyde4-Fluoro- 4' fluoro-3,5-dimethyl- 2.4(3H,s), 26(3H,s),phenyl [1,1'-biphenyl]-2-carbox- 7.0-7.4(6H,m), 10.0(1H,s) aldehyde4-Fluoro- 4'-fluoro-3,3'5,5'-tetra- 2.3(6H,d), 2.4(3H,s),3,5-dimeth- methyl-[1,1'-biphenyl]-2- 2.6(3H,s), 6.8-7.1(4H,m),ylphenyl carboxaldehyde 10.0(1H,s)______________________________________
EXAMPLE 39
3',4'-Dichloro-3,6-dimethyl-[1,1'-biphenyl]-2-carboxaldehyde
By substituting an equimolar amount of N-[(2,5-dimethylphenyl)methylene]benzeneamine in place of N-[(2,4-dichlorophenyl)methylene]benzeneamine in Step A of Example 34 and replacing the 4-fluorophenylmagnesium bromide with an equimolar amount of 3,4-dichlorophenylmagnesium bromide in Step B of Example 34 and following the procedures described therein, there was obtained a corresponding amount of the title compound as a pale yellow gum; pmr (CDCl 3 )δ2.0 (3H, s), 2.6 (3H, s), 7.0-7.6 (5H, m), 9.9 (H, s).
EXAMPLE 40
3-Chloro-4'-fluoro-3'-methyl-[1,1'-biphenyl]-2-carboxaldehyde
Step A: Preparation of N-[(2-chlorophenyl)methylene]benzeneamine
When the procedure of Example 36 Step A, is followed, except that an equimolar quantity of 2-chlorobenzaldehyde is used in place of 4-chloro-2-methylbenzaldehyde, there is obtained the title compound as a viscous oil.
Anal. Calc'd. for C 13 H 10 ClN: %C, 72.40; %H, 4.67; %N, 6.49. Found: % C, 72.35; %H, 5.02; % N, 6.46.
Step B: Preparation of 3-chloro-4'-fluoro-3'-methyl-[1,1'-biphenyl]-2-carboxaldehyde
By substituting an equimolar quantity of N-[(2-chlorophenyl)methylene]benzeneamine in place of N-[(2,4-dichlorophenyl)methylene]benzeneamine in Step A of Example 34 and replacing the 4-fluorophenylmagnesium bromide with an equimolar amount of 4-fluoro-3-methylphenylmagnesium bromide in Step B of Example 34 and following the procedures described therein, there is obtained the title compound, mp 74°-79° C.
Anal. Calc'd for C 14 H 10 ClFO: % C, 67.62; % H, 4.05. Found: % C, 67.83; % H, 4.09.
EXAMPLE 41
By substituting an equimolar amount of the following aldehydes for 2,4-dichloro-6-phenylmethoxybenzaldehyde in alternate to alternate Step B, Example 1, and then following Steps B through F of Example 1, the corresponding tetrahydropyran-2H-ones listed below were obtained.
EXAMPLE 41
__________________________________________________________________________ AnalysisStarting Aldehyde End Product mp Calcd. Found__________________________________________________________________________3,5-dichloro-4'-methyl- (E)-trans-6-{2-(3,5- 119°- C: 63.67 63.69[1,1'-biphenyl]-2-carboxal- dichloro-4'-methyl-2- 119.5° H: 4.81 4.88dehyde [1,1'-biphenyl]yl)- ethenyl}-3,4,5,6-tetra- hydro-4-hydroxy-2H--pyran- 2-one3,5-dichloro-4'-methoxy- (E)-trans-6-{2-(3,5- 100°-102° C: 61.08 C: 60.95[1,1'-biphenyl]-2-carboxal- dichloro-4'-methoxy-2- H: 4.61 H: 4.65dehyde [1,1'-biphenyl]yl)- ethenyl}-3,4,5,6-tetra- hydro-4-hydroxy-2H--pyran- 2-one3,5,-dichloro-3'-fluoro- (E)-trans-6-{2-(3,5- 130°-132° C: 59.86 59.75[1,1'-biphenyl]-2-carboxal- dichloro-3'-fluoro-2- H: 3.97 3.94dehyde [1,1'-biphenyl]yl)- ethenyl}-3,4,5,6-tetra- hydro-4-hydroxy-2H--pyran- 2-one3',4'-dichloro-3,5- (E)-trans-6-[2-(3',4' 128°-129° C: 64.46 C: 64.11dimethyl-[1,1'-biphenyl]- dichloro-3,5-dimethyl- H: 5.15 H: 5.162-carboxaldehyde 2-[1,1'-biphenyl]yl)ethenyl]- 3,4,5,6-tetrahydro-4-hydroxy- 2H--pyran-2-one3,5-dichloro-3'-methyl- (E)-trans-6-[2-(3,5- glass C: 62.84 C: 62.60[1,1'-biphenyl]-2- dichloro-3'-methyl- H: 4.75 H: 4.82carboxaldehyde 2-[1,1'-biphenyl]yl)ethenyl]- 3,4,5,6-tetrahydro-4-hydroxy- 2H-- pyran-2-one 0.05 M CHCl.sub.3 Solvate3,5-dichloro-3',5'- (E)-trans-6-[2-(3,5- glass C: 63.60 C: 63.99dimethyl-[1,1'-biphenyl]- dichloro-3',5'-dimethyl- H: 5.09 H: 5.262-carboxaldehyde 2-[1,1'-biphenyl]yl)ethenyl]- 3,4,5,6-tetrahydro-4-hydroxy- 2H--pyran-2-one 0.05 M CHCl.sub.3 Solvate3',4'-dichloro-3,6- (E)-trans-6[2-(3',4'-di- glass C: 64.46 C: 64.33dimethyl-[1,1'-biphenyl]- chloro-3,6-dimethyl-2-[1,1'- H: 5.15 H: 5.332-carboxaldehyde biphenyl]yl)ethenyl]- 3,4,5,6-tetrahydro-4-hydroxy- 2H--pyran-2-one3,5-dichloro-2'-methyl- (E)-trans-6-[2-(3,5-dichloro- 140°-141°C: 63.67 C: 64.04[1,1'-biphenyl]-2- 2'-methyl-2-[1,1' biphenyl]yl)- H: 4.81 H: 4.92carboxaldehyde ethenyl]-3,4,5,6-tetrahydro- 4-hydroxy-2H--pyran-2-one3,5-dichloro-4'-fluoro-2'- (E)-trans-6-[2-(3,5- glass C: 60.77 C: 60.99methyl-[1,1'-biphenyl]- dichloro-4'-fluoro-2'- H: 4.33 H: 4.362-carboxaldehyde methyl-2-[1,1'-biphenyl]yl)- ethenyl]-3,4,5,6-tetrahydro-4- hydroxy-2H--pyran-2-one3,5-dichloro-3'-ethyl- (E)-trans-6-[2-(3,5- gum C: 63.64 C: 63.28[1,1'-biphenyl]-2- dichloro-3'-ethyl-2-[ H: 5.09 H: 5.19carboxaldehyde 1,1'-biphenyl]yl)ethenyl]- 3,4,56-tetrahydro-4-hydroxy- 2H--pyran-2-one 0.05 M CHCl.sub.3 Solvate3,3',4',5-tetra- (E)-trans-6-[2-(3,3',4',5- glass C: 52.81 C: 3.27chloro-[1,1'-biphenyl] -2- tetrachloro-2-[1,1'-biphenyl]yl)- H: 52.49 H: 3.35carboxaldehyde ethenyl]-3,4,5,6-tetrahydro-4- hydroxy-2H--pyran-2-one3,3',5,5'-tetra- (E)-trans-6-[2-(3,3',5,5'- glass C: 52.81 C: 52.73chloro-[1,1'-biphenyl]- tetrachloro-2-[1,1'-biphenyl]yl)- H: 3.27 H: 3.372-carboxaldehyde ethenyl]-3,4,5,6-tetrahydro-4- hydroxy-2H--pyran-2-one3,5-dichloro-4'-fluoro- (E)-trans-6-[2-(3,5- glass C: 59.29 C: 59.493'-methyl-[1,1'-biphenyl] dichloro-4'-fluoro-3'- H: 4.23 H: 4.272-carboxaldehyde methyl-2-[1,1'-biphenyl]yl)- ethenyl]-3,4,5,6-tetrahydro-4- hydroxy-2H--pyran-2-one 0.1 M CHCl.sub.3 Solvate3,5-dichloro-3'-methoxy- (E)-trans-6-[2-(3,5- 93°-4° C: 61.08 C: 61.26[1,1'-biphenyl]-2- dichloro-3'-methoxy- H: 4.61 H: 4.79carboxaldehyde 2-[1,1'-biphenyl]yl)- ethenyl]-3,4,5,6-tetrahydro- 4-hydroxy-2H--pyran-2-one4'-fluoro-3,3',5- (E)-trans-6-[2-(4'-fluoro- 115°-116° C: 74.56 C: 74.79trimethyl-[1,1'-biphenyl]- 3,3',5-trimethyl-2-[1,1'- H: 6.54 H: 6.842-carboxaldehyde biphenyl]yl)ethenyl]- 3,4,5,6-tetrahydro-4-hydroxy-2H-- pyran-2-one3,3',5,5'-tetramethyl-[1,1'- (E)-trans- 6-[2-(3,3',5,5'- 109°-110° C: 78.83 C: 79.02biphenyl]-2-carboxaldehyde tetramethyl-2-[1,1'-biphenyl]- H: 7.48 H: 7.79 yl)ethenyl)-3,4,5,6- tettrahydro-4-hydroxy-2H-- pyran-2-one4'fluoro-3,5-dimethyl- (E)-trans-6[2-(4'-fluoro 154°- 156° C: 74.10 C: 74.50[1,1'-biphenyl]-2-carboxalde- 3,5-dimethyl-2-[1,1'-biphenyl]yl)- H: 6.22 H: 6.57hyde ethenyl]-3,4,5,6-tetrahydro- 4-hydroxy-2H--pyran-2-one3-chloro-4'-fluoro- (E)-trans-6-[2- glass3'-methyl-[1,1'-biphenyl]- (3-chloro-4'-fluoro-2-carboxaldehyde 3'-methyl-2-[1,1'-biphenyl]- yl)ethenyl]-3,4,5,6-tetrahydro- 4-hydroxy-2H--pyran-2-one5-chloro-4'-fluoro- (E)-trans-6-[2-(5- 109°-110° C: 67.29 C: 67.333,3'-dimethyl- chloro-4'-fluoro- H: 5.38 H: 5.42[1,1'-biphenyl]-2- 3,3'-dimethyl-carboxaldehyde 2-[1,1'-biphenyl]yl)- ethenyl]-3,4,5,6-tetra- hydro-4-hydroxy-2H--pyran- 2-one4'-fluoro-3,3',5,5'-tetra- (E)-trans-6-[2-(4'- 142°-146° C: 74.98 C: 75.20methyl-[1,1'-biphenyl]- fluoro-3,3',5,5'-tetra- H: 6.84 H: 7.232-carboxaldehyde methyl-2 -[1,1'-biphenyl]- yl)ethenyl]-3,4,5,6- tetrahydro-4-hydroxy-2H-- pyran-2-one__________________________________________________________________________
EXAMPLE 42
Resolution of the Optical Isomers of (±) Trans-6-{2-[2,4-dichloro-6-(4-fluorophenylmethoxy)phenyl]ethyl}-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
Step A. Preparation and Separation of the Diastereomeric Amides (Diastereomers A and B)
A solution of (±)-trans-6-{2-[2,4-dichloro-6-(4-fluorophenylmethoxy)phenyl]ethyl}-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (28.3 g, 68 mmole) and 1-(-)-α-methylbenzylamine (16.5 g, 136 mmole) in tetrahydrofuran (350 ml) was refluxed for 20 hours. The tetrahydrofuran was removed in vacuo and the residue was stirred in ether (500 ml) and the precipitate collected to give diastereomer A which was twice stirred for 15 min. in refluxing ether (500 ml) to yield a colorless solid (13.0 g, 36%) which melted at 185°-188° C.
Step B. Preparation of (+) Trans-6-{2-[2,4-dichloro-6-(4-fluorophenylmethoxy)phenyl]ethyl}-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
By substituting an equimolar amount of diastereomer A from Step A above for diastereomer A in Step B of Example 13 and following the procedure described therein, there was obtained a corresponding amount of the title compound which was recrystallized from n-butylchloride-pet ether (4:3, v:v), mp 133°-135° C.; pmr (CDCl 3 ) δ1.53-2.20 (5H, m); 2.66 (2H, m), 2.93 (2H, m), 4.36 (H, m), 4.73 (H, m), 5.04 (2H, s), 6.85 (H, d), 7.03-7.53 (5H, m).
Analysis Calc. for C 20 H 19 Cl 2 FO 4 . Calc: C, 58.12; H, 4.63. Found: C, 58.25; H, 4.71.
[α] D 25 +17.8° (C, 1.0; chloroform).
EXAMPLE 43
Preparation of (+)-(E)-(3R*, 5S*)-7-(3,5-dichloro-4'-fluoro[1,1'-biphenyl]-2-yl)-3,5-dihydroxy-6-heptenoic acid, ammonium salt
Step A. Preparation and Separation of Diastereomeric Amides
By substituting an equimolar amount of (±)-trans-(E)-6-{2-[3,5-dichloro-4'-fluoro[1,1'-biphenyl]-2-yl)ethenyl}-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one for (±)-trans-6-{2-[2,4-dichloro-6-(4-fluorophenylmethoxy)phenyl]ethyl}-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one in Step A of Example 42 and following the procedure described therein there was obtained a corresponding amount of Diastereomer A as colorless crystals which melted at 128.5°-129° C.
Step B. Preparation of (+)-(E)-(3R*, 5S*)-7-{3,5-dichloro-4'-fluoro[1,1'-biphenyl]-2-yl}-3,5-dihydroxy-6-heptenoic acid, ammonium salt
Diastereomer A (6.2 g, 12.3 mmole) of Step A was dissolved in 95% ethanol (600 ml) containing 1N NaOH (60 ml, 60 mmole) and the solution was refluxed for 16 hours. The solvent was removed in vacuo and the residue was suspended in ice water (200 ml) and ether (500 ml) and subsequently acidified with 3N HCl (50 ml). The ether layer was washed successively with ice-cold 1N HCl (200 ml), brine (2×200 ml), dried over MgSO 4 , and filtered. Anhydrous ammonia was bubbled through the cold etherial solution for 2 min. Vigorous stirring was then continued at 20° C. for 1 hour and then the mixture was cooled slowly to ca 5° C. Filtration provided the title compound as tiny colorless needles (4.3 g, 84%), mp 105°-108° C. dec. pmr (d 6 -DMSO)δ 1.15 (H, m), 1.41 (H, m), 1.99 (H, dd), 2.14 (H, dd), 3.66 (H, m), 4.11 (H, dd), 5.52 (H, dd) 6.38 (H, d), 7.23-7.42 (5H, m), 7.69 (H, d).
Analysis for C 19 H 20 Cl 2 FNO 4 . Calc: C, 54.82; H, 4.84; N, 3.36. Found: C, 55.13; H, 4.98; N, 3.07.
[α] D 27 =+10.75° (C, 1.6; water).
Employing the procedure of Example 43 the other 6-(biphenylethenyl)-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-ones of Example 41 are resolved into their dextro- and levoratatory enantiomers, the 4(R)-enantiomer (usually the dextrorotatory) having the antihypercholesterolemic activity.
EXAMPLE 44
Ethyl E-(3R,5S)-7-(4'-Fluoro-3,3',5-trimethyl[1,1'-biphenyl]-2-yl)-3,5-dihydroxy-6-heptenoate
(E)-trans-6-[2-(4'-fluoro-3,3',5-trimethyl-[1,1'-biphenyl]-2-yl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (100 mg, 2.82×10 -4 mole) was dissolved in 5 mL of methanol.sup.(1) and treated with 0.3 mL of 1.0N aqueous sodium hydroxide solution. After stirring for one hour under nitrogen at ambient temperature, the reaction mixture was concentrated to dryness under vacuum and the residue was dried by azeotropic distillation of a little toluene.
The crude residue was dissolved in 2 mL of DMF and treated with 0.04 g (2.963×10 -4 mole) of K 2 CO 3 and 0.04 mL (0.078 g, 5×10 -4 mole, d=1.95) of ethyl iodide, and stirred for about 24 hours at room temperature. The mixture was diluted with about 60 mL of diethyl ether, washed with water (3×25 mL) and saturated brine (2×10 mL) and concentrated to dryness in vacuo to give 94 mg of crude product. The crude product was chromatographed on a 20 mm flash chromatography (silica gel 230-400 mesh) colmun by elution with 8% (v/v) acetone in methylene chloride.sup.(2) to give 40 mg of product, m.p. 65°-67° C.
Note: .sup.(1) Reaction may be conducted in other alcohols, especially ethanol. .sup.(2) Eluant may also be 7% (v/v) isopropanol in hexane.
Similarly prepared are the methyl, n-propyl, 2-(acetylamino)ethyl, and 1-(2,3-dihydroxypropyl)esters of E-(3R,5S)-7-(4'-fluoro-3,3',5-trimethyl[1,1'-biphenyl]-2-yl)-3,5-dihydroxy-6-heptenoic acid. | The methyl, ethyl, n-propy, 2-(acetylamino)ethyl, or 1-(2,3-dihydroxy)propyl ester of E-(3R,5S)-7-(4'-fluoro-3,3',5-trimethyl[1,1'-biphenyl]-2-yl)-3,5-dihydroxy-6-heptenoic acid of structural formula: ##STR1## are HMG-CoA reductase inhibitors useful in the treatment of conditions associated with hypercholesterolemia. | 2 |
The present application claims priority under 35 U.S.C. §119 and/or §365 to Patent Application Serial No. 06/08124 filed in France on Sep. 14, 2006, the entire content of which is incorporated herein.
BACKGROUND
The invention relates to the field of the extrusion of plastic or viscoelastic materials and, in particular, to the field of the extrusion of rubbery materials.
Industrial use of these materials, before they are shaped by injection moulding or by feeding them through a die, requires these materials to be homogenized as fully as possible both in terms of temperature and in terms of viscosity so as to gain control over the mechanical properties of the end-product.
Conventional extrusion methods for ensuring these functionalities comprise a screw in which the shape of the flight is designed to cause the material to circulate, while breaking up and recombining the streams. They may comprise a filter screen pack positioned downstream of the stream, so as to remove undesirable foreign substances.
These methods are generally very penalizing in terms of the flow rate and temperature performance of the extrusion means, because of the high pressure drops they cause. This penalty is all the worse if a filter system is added, because the build-up of substances may block the filters, making operation more difficult.
Already known in the prior art is an extrusion device comprising two or more kneading and conveying screws positioned coaxially and concentrically with respect to one another in the same body, in which the flight trough of a larger-diameter screw has orifices allowing the space swept by the flight of the larger-diameter screw to communicate with the space swept by the flight of the immediately adjacent smaller-diameter screw. This type of device is described by way of example in patent FR 1 270 314 or alternatively in patent FR 2 008 656 (corresponding to Schippers U.S. Pat. No. 3,583,684).
Such devices are able to achieve a certain level of homogenization but are restricted in this action in as much as the material passes directly from the space swept by the flight of the larger-diameter screw into the space swept by the flight of the immediately adjacent smaller-diameter screw. Furthermore, because of this type of layout, the screws have to turn at different speeds from one another so as to provide the work necessary for transferring the material. This leads to complex mechanical layouts, particularly when it is desirable to produce a device comprising more than two concentric screws.
Also known, from publications Meskat et al. U.S. Pat. No. 2,948,922 or SU 1 498 623, are a device and a method in which a larger diameter screw and a smaller diameter screw are arranged coaxially and telescopingly. The flight trough of the larger diameter screw has orifices which open into a space disposed radially between the telescoping screw portions. A fixed cylindrical apertured tube is interposed between a space swept by the flight of the smaller-diameter screw and said space into which the orifices open. However, these devices have the disadvantage of not easily allowing substances larger in size than the orifices made in the cylindrical tube to be removed without the need to shut the device down in order to carry out an operation of emptying and unclogging the filter.
SUMMARY OF PREFERRED EMBODIMENT
The device according to the invention, which is intended for extruding and filtering a viscoelastic material, is designed to overcome this disadvantage. This device preferably comprises kneading-and-conveying screws positioned coaxially and concentrically in a body, in which the flight trough of a larger-diameter screw has orifices allowing the space swept by the flight of the larger-diameter screw to communicate with the space swept by the flight of the smaller-diameter screw.
A fixed cylindrical tube comprising apertures passing through the wall of the cylindrical tube is inserted between the space swept by the flight of the smaller-diameter screw and the space into which the orifices open. The space swept by the flight of the larger-diameter screw is closed off by a wall so that when the device is operating, the material is forced into the orifices and then into the apertures. The wall has an orifice communicating with an outfall closed off by a removable blanking means.
The cylindrical tube acts as a filter plate, the size of the apertures of which need to be calibrated such as to set the size of the particles of material that are to be filtered out.
Acting in this way makes it possible for substances with a diameter greater than the size of the orifices to be concentrated at the end of the space swept by the flight of the larger-diameter screw and communicating with the outfall. All that is then required is for the outfall to be opened so that the end region can be emptied and the undesirable particles expelled without the need to interrupt the operation of the machine.
Acting in this way also makes it possible to improve the homogenization of the material. This is because the stream is split for a first time as it passes through the orifices, and is then split a second time as it enters the apertures made in the cylindrical tube, before being carried along by the flight of the smaller-diameter screw.
In addition, the material undergoes significant shear as it passes between the various components because of the relative movements of these components with respect to one another.
It is also found that this capacity for homogenization, for mechanical work and for filtration is obtained with a pressure drop that is relatively limited because of the low magnitude of the distances, known as passive distances, over which the material is displaced solely under the action of the pressure obtaining upstream. This passive distance is formed, to a first approximation, by the length of the orifices passing through the flight trough of the larger-diameter screw and by the thickness of the cylindrical tube. This small amount of pressure drop has the effect of limiting the increase in the temperature of the material.
Finally, bearing in mind the fact that the cylindrical tube is not rotationally driven, the cylindrical tube acts as the internal wall of the body of an extruder. It is therefore possible for the screws to be rotated at the same rotational speed, allowing these components to be secured to one another, and driven using a common mechanical device. The layout and construction of such a system are therefore greatly simplified by this, by comparison with the layout and construction of known systems.
BRIEF DESCRIPTION OF DRAWINGS
The description which follows will reveal the other advantages of a method and a device for homogenizing and filtering according to the invention.
FIG. 1 depicts a schematic longitudinally sectioned view of the preferred embodiment.
FIG. 2 is a fragmentary view of the cylindrical tube, showing slot-shaped apertures therein.
FIG. 3 is a fragmentary view of the cylindrical tube showing flared-shaped apertures.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The device illustrated in FIG. 1 comprises an extruder body 1 mounted on a chassis (not depicted). A screw 2 comprising a core and a helical flight 21 projecting from the core is rotationally driven about an axis A by a conventional drive assembly (not depicted). A conventional feed system (not depicted) positioned upstream introduces the viscoelastic material into the device. The shape of the flight 21 , here depicted schematically, is tailored to the flow rate and temperature that are to be obtained at the outlet of the device, using methods known to those skilled in the art.
When the device is operating, the stream of material flows in the direction of the arrow F within an internal space S 1 swept by the helical flight 21 of the screw 2 , i.e., a space S 1 situated between the interior wall 1 a of the body 1 of the extruder and the floor of the trough 21 a of the screw flight 21 . This space S 1 is closed off at its axial downstream end by a wall 43 which enables the stream of material to be forced through radial orifices 22 made in the floor of the trough of the flight 21 . The wall 43 is part of a sleeve 7 mounted in such a way as to be stationary with respect to the body 1 .
The portion of the flight trough 21 situated in the downstream part of the screw 2 has orifices 22 which fluidly interconnect the space S 1 with an internal space formed within a hollow section 2 a of the core of the screw 2 .
The result of this is that the stream F is forced, under the effect of the feeding pressure, through the orifices 22 and towards the internal space formed by the radially inner surface of the core's hollow section 2 a.
Telescopingly or concentrically arranged within the hollow section 2 a of the core is an end of a screw 3 , of smaller diameter than the screw 2 , the axis of rotation of which coincides with the axis of rotation of the larger-diameter screw 2 . Disposed radially opposite the orifices 22 is a space S 2 swept by the flight 31 of the smaller-diameter screw 3 . The space S 2 has an outer diameter D 2 which is less than the inside diameter of the hollow core section 2 a of the larger diameter screw 2 .
The device is supplemented by a head 5 , removably secured to the body 1 and situated in the downstream part of the device. The body 1 , the sleeve 7 and the head 5 together define a housing.
A fixed cylindrical tube portion 4 , which is integral with the sleeve 7 , is inserted radially between the space S 2 swept by the flight 31 of the smaller-diameter screw 3 and the space of the hollow core section 2 a into which the orifices 22 open. This cylindrical tube has apertures 41 passing radially therethrough such that the stream F is directed from the orifices 22 through the apertures 41 so that it can be taken up by the flights 31 of the smaller-diameter screw 3 which mix the material once again and direct it towards the outlet of the device. The apertures 41 are spaced apart along the telescoping zone of the screws 2 , 3 which coincides with the hollow section 2 a of the core of the screw 2 .
As has already been stated above, these multiple fragmentations of the stream F via the orifices 22 and the apertures 41 have the effect of improving the homogenization effect without causing the material to be heated significantly. The path from the screw 2 to the screw 3 , termed the passive path, during which the material is propelled under the sole effect of the pressure generated by the larger-diameter screw, may be extremely short and be reduced essentially to the thickness of the cylindrical tube, which thickness may range between 1 and 10 mm.
Efforts will also be made to minimize the thickness of the cylindrical tube 4 in order to make it easier to empty out the device before a shut-down phase, so as to minimize the amount of material remaining in the device.
The apertures 41 made in the cylindrical tube may be of extremely variable size and shape according to whether it is desirable simply to homogenize or to filter the material.
On the other hand, when the device is used as a homogenizer, the shape of the apertures 41 is designed to separate the streams of material passing through the flight 21 of the larger-diameter screw as effectively as possible. A slot shape for the apertures 41 , as shown in FIG. 2 , appears to afford the best efficiency, and the angle α that the slot makes with the direction of the generatrices of the cylindrical tube needs to be tailored to suit the rotational speed of the screws, the angle α ranging between 0° and 90° with respect to the direction of the generatrices of the cylindrical tube.
By sufficiently reducing the size of the apertures 41 , the device then acts as a filter. The size of the apertures, which may advantageously adopt the shape of circular cylindrical holes, may be small, if care is also taken to increase the number of the apertures 41 so as not to penalize such a filter device by imposing too high a pressure drop.
In order to reduce the pressure drop across such filter, it is possible to give the walls of the apertures 41 a flared shape so that the cross section of the aperture increases in the direction in which the material progresses through the filter, as shown in FIG. 3 . It is thus possible to hold the undesirable substances back, upstream of the filter, while at the same time encouraging the material to pass into the aperture.
This pressure drop may be further reduced by increasing the diameter of the larger-diameter screw 2 at the downstream transfer region, the increase in diameter being accomplished gradually, beginning at point 70 illustrated in FIG. 1 . This measure makes it possible to increase the overall surface area of the filter with respect to the flow rate of the device.
The sleeve 7 is equipped with a duct 42 which passes through the wall 43 and continues in the region of the head 5 in the form of an outfall or outlet duct 52 , which communicates with a discharge member 6 forming a duct 62 that is closed off by a removable closure or blanking element 61 .
The particles unable to pass through the apertures 41 in the tube 4 are mechanically reduced by the movement of the internal part of the larger-diameter screw 2 around the cylindrical tube 4 until they are small enough in size to pass through an aperture 41 . If the particle cannot be sufficiently reduced, it is instead pushed towards the downstream end of the tube in the direction of the wall 43 where such particles accumulate.
To discharge the particles while the device is operating, it is merely necessary for the blanking element 61 to be removed so that the space in which these contaminants have accumulated can be emptied, i.e., the accumulated particles are pushed out through a discharge passage formed by the ducts 42 , 52 , 62 . This then prevents the apertures 41 made in the cylindrical tube 4 from becoming blocked, eliminating the need to interrupt the operation of the device in order to change or clean the filter.
In order to make it easier to assemble all the components, the sleeve 7 is removable. Thus, the cylindrical tube 4 can be removed simply by removing the extrusion head 5 , e.g. by removing fastener screws (not shown) which secure the extrusion head 5 and the sleeve 7 to the body 1 .
Another advantage of the device according to the invention is that it is possible to turn the screws 2 , 3 at the same rotational speed. This is because each of the screw flights drives the material along in a translational movement with respect to a fixed wall. This effect is obtained by the flight 21 with respect to the interior wall of the body 1 , and in the same way, by the flight 31 with respect to the interior wall of the cylindrical tube 4 .
It is then easy to secure the screws 2 , 3 to one another by positioning them concentrically and coaxially with respect to one another and interconnecting them, preferably in axial abutment with one another. Thus, only the larger-diameter screw 2 needs to be connected to a driving member, thereby greatly simplifying the production of the device.
It is also possible to produce an assembly comprising several successive stages by extending the head 5 of the body 1 and by making orifices in the downstream part of the screw 3 to allow the space swept by the flight 31 of the screw 3 to communicate with an internal space formed in the core of the screw 3 which would work in conjunction with a smaller-diameter screw (not depicted in FIG. 1 ).
This cascade of screws successively collaborating one with the next may also be produced in a very compact form by making the screws concentric (i.e., telescoping).
It is then possible to assign more specific functions to the various cylindrical tubes by devoting larger-diameter tubes 4 to filtration functions and smaller-diameter tubes 4 to homogenization functions or alternatively to size the orifices 22 in such a way as to filter out substances of increasingly small size.
Likewise, it is possible to vary the diameter of the various screws or, alternatively, to make the screws conical in shape. It may thus be readily appreciated that the diameter of the screw 3 can increase again downstream of that part of the device in which this screw collaborates with the screw 2 .
Any number of the screws 2 , 3 can be arranged axially along the extrusion path to provide a number of areas where the extruding material passes sequentially through a first space S 1 , orifices 22 , apertures 41 and a second space S 2 . | A viscoelastic material is extruded by kneading-and-conveying screws of different respective diameters positioned coaxially and telescopingly. A flight trough of a larger-diameter screw has radial orifices allowing a first space swept by the flight of the larger-diameter screw to communicate with a second space swept by a flight of a smaller-diameter screw. A fixed cylindrical tube arranged coaxially with the screws is disposed radially between the first and second spaces within the region in which the screws telescope. The tube has radial apertures therethrough to conduct material from the orifices to the second space. The first space is closed off at an axial end thereof by a wall where foreign substances accumulate that do not pass through the orifices. A passage through the wall can be opened to remove the accumulated substances without interrupting the extrusion operation. | 1 |
TECHNICAL FIELD
[0001] The present disclosure relates to safety features for vehicles, and in particular features that mitigate body side intrusions in side impact collisions.
BACKGROUND
[0002] A vehicle door may consist of an outer panel facing the exterior of the vehicle and an inner panel facing the cabin of the vehicle. The inner panel includes a lower wall that faces a rocker assembly. In a side impact collision, vehicle doors may collapse inwardly and intrude into the cabin of the vehicle. Excessive door intrusion may adversely affect deployment of a side air bag due to the reduced gap between the door and the occupant.
[0003] Some safety structures may attempt to minimize the door intrusion into the cabin from a side impact collision. Such a structure is disclosed in U.S. Pat. No. 4,462,633. U.S. Pat. No. 4,462,633 discloses a box shaped reinforcing member mounted on a vehicle floor that extends above the side sill or rocker panel. A bracket mounted to the door has a portion engaging the reinforcing member when the door is closed. In a side impact collision, the bracket engages the reinforcing member to inhibit inward movement of the door. The box shaped reinforcing member is visible to an occupant, especially when the door is open. An occupant must step over the rocker panel when entering or exiting the vehicle. A box shaped reinforcing member that is disposed above the rocker panel interferes with the ingress and egress of the occupant. Placing a box shaped reinforcing member above the rocker panel also limits design freedom. The receiver must be of a limited size to reduce interference with the ingress and egress of the occupant.
[0004] The above problems and other problems are addressed by this disclosure as summarized below.
SUMMARY
[0005] One aspect of the present disclosure relates to an apparatus for resisting intrusion of a door into a passenger compartment of a vehicle that has a rocker. The apparatus includes a projection extending horizontally from the door and a catcher that is provided on the rocker. The rocker includes a vertically extending wall. When the door is closed, the catcher receives a portion of the projection to hold the door in engagement with the vertically extending wall of the rocker.
[0006] Other aspects of the above apparatus include a reinforcement panel attached to an inner side of an inner panel of the door for supporting the projection. A grommet may be attached to the vertically extending wall of the rocker. The grommet surrounds the catcher and defines a slit extending substantially throughout a length of the catcher. The slit receives the projection when the door is closed. The rocker may include a rocker reinforcement panel attached to the rocker to reinforce the rocker about the catcher.
[0007] The projection of the apparatus may be a loop that includes two legs that are each attached to the reinforcement panel by its respective foot. The door may include an inner panel, and the projection may include a first leg and a second leg extending horizontally and inwardly from the inner panel of the door. The projection also includes a cross-piece connecting a distal end of the first leg to a distal end of the second leg. The reinforcement panel of the apparatus may be attached to the inner panel, wherein the first leg and the second leg are attached to the reinforcement panel at their ends that are opposite their distal ends to support the projection.
[0008] Another aspect of the present disclosure relates to a vehicle body that includes a rocker and a door connected to the vehicle body above the rocker. The door is moveable between an open position and a closed position. The door includes an outer panel and an inner panel attached to the outer panel. The inner panel includes a rocker engaging portion that faces the rocker when the door is in the closed position and a projection attached to the rocker engaging portion. The projection protrudes from the rocker engaging portion. The rocker defines a catcher opening that receives the projection when the door is closed to inhibit the door from moving inboard in a side impact collision.
[0009] The inner panel of the vehicle body may include a door trim portion disposed above the rocker engaging portion. The projection of the vehicle body may be a U-shaped member, a loop, or it may include a first leg extending from the inner panel portion and a second leg also extending from the inner panel portion. The projection may also include a cross-piece perpendicularly attached to the first leg and the second leg.
[0010] The vehicle body may also include a reinforcement panel attached to the inner panel. The vehicle body may further include a reinforcement panel attached to the rocker and disposed on the rocker at an area where the catcher is formed. The vehicle body may also include a floor side inner attached to the vehicle body. The floor side inner and the rocker form a catcher cavity. When the door is closed, a portion of the projection is positioned within the catcher cavity.
[0011] Yet another aspect of the present disclosure relates to a door intrusion resistance apparatus for a vehicle that includes a door including a protrusion and a rocker defining a receptacle that receives the protrusion when the door is closed. In a side impact collision with the door, the door is inhibited from moving above the rocker by the protrusion being received in the receptacle to hold the door against the rocker.
[0012] The protrusion of the door intrusion resistance apparatus may extend horizontally from an inner panel of the door inboard of the vehicle. The protrusion is also positioned below a door trim so that when the door is closed, the protrusion is not visible to an occupant. The rocker of the door intrusion resistance apparatus may also include a wall that extends in a vertical direction. The wall defines the receptacle that receives the protrusion when the door is closed.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] FIG. 1 is a perspective view of a vehicle incorporating a door intrusion resistance apparatus of the present disclosure.
[0014] FIG. 2A is a partial perspective view of a lower inner portion of a front door illustrating a projection.
[0015] FIG. 2B is a close up view of FIG. 2A showing how the projection extends through the inner door.
[0016] FIG. 3A is a partial perspective view of the opposite side of the lower inner portion of FIG. 2A illustrating a reinforcement panel attached to the lower inner portion.
[0017] FIG. 3B is a close up view of FIG. 3A illustrating the legs of the projection with feet that anchor the projection to the door.
[0018] FIG. 4 is a partial side elevation view of the rocker panel illustrating the catcher provided on the rocker.
[0019] FIG. 5 is a cross-sectional view of the rocker panel taken along the lines 5 - 5 in FIG. 4 .
[0020] FIG. 6 is a partial perspective view of the rocker panel illustrating the catcher provided on the rocker and the grommet covering the catcher.
[0021] FIG. 7 is a partial perspective view of the rocker panel of FIG. 6 with the projection engaging the catcher.
[0022] FIG. 8 is a cross-sectional view taken along the line 8 - 8 in FIG. 1 showing the door intrusion resistance apparatus.
DETAILED DESCRIPTION
[0023] The illustrated embodiments are disclosed with reference to the drawings. However, it is to be understood that the disclosed embodiments are intended to be merely examples that may be embodied in various and alternative forms. The figures are not necessarily to scale and some features may be exaggerated or minimized to show details of particular components. The specific structural and functional details disclosed are not to be interpreted as limiting, but as a representative basis for teaching one skilled in the art how to practice the disclosed concepts.
[0024] Referring to FIG. 1 , a vehicle 22 incorporating the door intrusion resistance apparatus includes a front door 24 attached to a vehicle body adjacent to the A-pillar 26 . The vehicle 22 also includes a rear door 28 attached to the vehicle body near the B-pillar 30 . Door 24 includes an upper outer portion 32 and a lower outer portion 34 . The door intrusion resistance apparatus may be incorporated with any of the doors of the vehicle 22 .
[0025] Referring to FIG. 2A , door 24 includes an upper inner portion 36 and an upper outer portion 32 . In between the upper inner portion 36 and the upper outer portion 32 is a cavity 38 where vehicle accessories may be mounted, such as those for opening and closing the doors and windows, for defrosting the windows, and audio speakers. The accessories may be covered by a door trim or an interior trim panel that may be another inboard side panel mounted to the upper inner portion. Door 24 also includes a lower inner portion 42 disposed below the upper inner portion 36 . The upper inner portion 36 may have an overhang or an offset surface from the lower inner portion 42 to encapsulate the accessories within the cavity formed by the upper inner portion 36 and the upper outer portion 32 . A door seal 40 is attached between the upper inner portion and the lower inner portion. When the door 24 is in a closed position, the lower inner 42 is not visible to an occupant of the vehicle.
[0026] The door intrusion resistance apparatus includes a projection 44 connected to the lower inner portion 42 and extends or protrudes substantially horizontally from the lower inner portion 42 . Thus, the term “protrusion” may also sometimes be used to refer to the projection 44 . The projection 44 may be disposed at a slight angle relative to the lower inner portion 42 . The projection 44 is positioned below the door seal 40 and is in a form of a loop or a U-shaped member. Projection 44 includes a pair of parallel legs 46 a and 46 b that extend through the lower inner 42 , and a cross-piece 43 is attached to the distal ends of the legs 46 a and 46 b ( FIG. 2B ).
[0027] Legs 46 a and 46 b extend through holes that are formed on the lower inner portion 42 and on a reinforcement panel 50 attached to the lower inner 42 ( FIG. 3A ). The reinforcement panel 50 may be made of steel and adds supporting structure that provides rigidity to the lower inner portion so that the projection 44 is not easily detached from the lower inner portion. In addition, the reinforcement panel 50 is adapted to resist crumpling of the lower inner portion in a side impact collision. Referring to FIG. 3B , a first foot 52 a is preferably connected to leg 46 a, and a second foot 52 b is connected to leg 46 b. The first foot 52 a and the second foot 52 b are substantially perpendicularly connected to their respective legs. The first foot 52 a and the second foot 52 b abut the door reinforcement panel 50 to attach and secure the projection 44 to the lower door panel. The feet may also be flattened at their ends to enhance the attachment of the projection 44 to the lower door panel. The projection 44 is attached to the lower inner portion 42 and is not visible to an occupant of the vehicle when the door 24 is closed. This location of the projection 44 provides flexibility in designing and determining the size of the projection 44 because it does not negatively impact the appearance of the door.
[0028] The term “rocker assembly” may be interchanged with the term “rocker” to refer to a portion of the body paneling of a vehicle that is situated below the doorsills of the vehicle. Referring to FIGS. 4-5 , a rocker assembly 56 includes an outer wall 57 . The outer wall 57 includes a top wall 45 , a bottom wall 47 that is positioned below the top wall 45 , and a vertically extending wall 49 connected to the top wall 45 and the bottom wall 47 . The top wall 45 may provide a door threshold for the vehicle and may be substantially horizontal. In certain embodiments, it is parallel with a vehicle floor. The bottom wall 47 serves as the base of the vehicle body and is a part of the periphery of the vehicle body. The vertically extending wall 49 contacts the lower inner portion 42 of the door 24 when the door is in a closed position.
[0029] The rocker assembly 56 also includes an inner wall 59 opposite the outer wall 57 . The rocker assembly 56 includes a door reinforcement panel 61 attached to the inner wall 59 . The door reinforcement panel 61 may be made of steel. The door intrusion resistance apparatus of the present disclosure includes a catcher 54 that is formed as an opening on the rocker assembly 56 and a reinforcement panel 61 attached to the inner wall 59 of the rocker assembly 56 . More specifically, the catcher 54 is formed on the vertically extending wall 49 of the rocker assembly 56 . The catcher 54 is shaped to receive the projection 44 . For instance, the catcher 54 may be elliptical in shape and may have a semi-major axis diameter that is larger than the width of the cross-piece 43 of the projection 44 . The catcher 54 may also be a rectangular opening that has a length that is larger than the width of the cross-piece 43 of the projection 44 . Referring to FIG. 6 , a grommet 58 , such as those made of rubber material, may be positioned around the opening of the catcher 54 to seal the catcher and minimize water intrusion to the catcher 54 . The grommet 58 includes a slit 60 extending substantially throughout the length of the catcher 54 to receive the projection 44 . The slit 60 may be single-lined slit across the middle of the catcher that diverges into a V-shaped slit at both ends. In FIG. 7 , when the door is closed, a portion of the projection 44 is inserted through the slit 60 of the grommet 58 , the catcher 54 , and the reinforcement panel 61 that is attached to the inner wall 59 of the rocker assembly 56 .
[0030] Referring to FIG. 8 , looking from the rocker assembly, a portion of the projection 44 is preferably received in a cavity 63 that is formed by the rocker assembly 56 and a floor side inner portion 64 of a vehicle. The rocker assembly 56 includes an inner wall 59 where the reinforcement panel 61 is attached. The reinforcement panel 61 may be attached to an area of the inner wall 59 that defines the catcher 54 . Looking from the lower inner portion 66 , the projection 44 of the door intrusion resistance apparatus of the present disclosure is attached to an inner panel of the door, and more specifically the lower inner portion 66 that is below the upper inner portion 68 . Thus, the lower inner portion 66 serves as a rocker engaging portion that faces the rocker. When the door is in a closed position, the upper inner portion 68 is disposed on top of the rocker assembly 56 , more specifically the top wall 45 of the rocker assembly. The upper inner portion 68 may contact a primary door seal 78 that is attached at the boundary of the rocker assembly 56 and the floor side inner portion 64 . The lower inner portion 66 is enforced by an inner reinforcement panel 70 attached to an area of the lower inner portion where the projection 44 is attached. As further shown in FIG. 5 , the projection 44 is attached to the inner panel portion, which is opposite to the outer panel portion 72 . The lower inner portion 66 where the projection 44 is attached is above a rocker molding 74 , and a secondary door seal 76 may be provided at the boundary of the lower inner portion 66 and the rocker molding 74 . A portion of the projection is received in the catcher and is positioned within the catcher cavity defined by the rocker assembly and the floor inner portion when the door is closed. Movement of the door towards the cabin of the vehicle (door intrusion) is inhibited or at least minimized in a side impact collision because the projection and the catcher hold the door in engagement with the rocker assembly.
[0031] A door intrusion resistance apparatus is provided that is discreetly positioned on a door of a vehicle that does not adversely impact the appearance of the door. The door intrusion resistance apparatus does not adversely impact ingress and the egress of vehicle occupants. The door intrusion resistance apparatus utilizes a catcher defined by an opening in the rocker assembly for receiving the projection. No hooks, boxes, or structures protrude from the rocker assembly that can impact the ingress and egress of the vehicle users.
[0032] While exemplary embodiments are described above, it is not intended that these embodiments describe all possible forms of the disclosed apparatus and method. 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 disclosure as claimed. The features of various implementing embodiments may be combined to form further embodiments of the disclosed concepts. | A vehicle body and a door intrusion resistance apparatus for a vehicle with a door that includes a protrusion and a rocker defining a receptacle that receives the protrusion when the door is closed. The door is inhibited from moving above the rocker by the protrusion being received in the receptacle that holds the door against the rocker in a side impact collision. | 1 |
CROSS REFERENCE TO RELATED APPLICATION
This is a continuation of application Ser. No. 399,201, filed Sept. 20, 1973, now U.S. Pat. No. 3,889,008, which is a continuation-in-part of prior, copending Ser. No. 36,666, filed May 12, 1970 and now U.S. Pat. No. 3,787,592.
BACKGROUND OF THE INVENTION
This invention relates to volatile food flavoring compounds such as flavors, flavor enhancers, aromas, and aroma enhancers, and more particularly to volatile flavoring compounds such as acetaldehyde, fixed in crystalline food materials such as sucrose to form solid flavoring compositions which are stable under normal shelf storage conditions, but which release flavoring when combined with either hot or cold water.
It has been known for some time that flavoring compounds such as acetaldehyde are important flavor components of natural fruits and vegetables and serve as flavor enhancers for the various flavor notes naturally present in meats, fruits and vegetables. Particularly, it has been found that acetaldehyde is very important in increasing the impact and freshness of certain flavors, such as fruit-type flavors. However, while the presence of acetaldehyde would be a valuable enhancer to a synthetic flavoring composition for use with a food formulation employing fruity-type flavors, it is difficult to incorporate acetaldehyde into a stable, solid flavor fixative. Most attempts to fix acetaldehyde in various compositions have tended to be unstable in the presence of small amounts of water or water vapor. This stability problem was apparent when powdered dessert and beverage products containing the fixed acetaldehyde were processed or packaged in a manner allowing atmospheric or product moisture to reach the fixed acetaldehyde during storage of the product. This problem is particularly acute when a fruit-type dessert or beverage formulation using a fixed acetaldehyde flavor is packaged in dry form in a non-hermetically sealed paper envelope or container which is sufficiently pervious to allow atmospheric moisture to enter and release acetaldehyde.
Acetaldehyde is chemically very reactive; it is very soluble in water; and it has a low boiling point (21°C). It exists as a gas at normal room temperature and pressure. It, furthermore, is readily oxidized to form acetic acid, and it easily polymerizes to form paraldehyde and metaldehyde. Thus, the problem confronting the food industry in augmention the flavor and aroma of dry powdered mixes has been that of "fixing" acetaldehyde in a sufficiently stable state to avoid volatization and/or chemical reaction during storage. It also is necessary to limit the degree of fixation to permit the release of the acetaldehyde compound during the normal household preparation of rehydrating or otherwise preparing a finished table product from the powdered mix (e.g. by addition of either hot or cold water).
Generally speaking, there are two methods of "fixing" acetaldehyde to insure improvement in shelf stability. One method is to chemically react the acetaldehyde with another material to form a more stable compound. The second method is to physically entrap or coat the acetaldehyde with a stable compound such as sugar, gum or other edible material.
With respect to the first method -- that of forming a more stable compound -- the resulting composition must not only have a degree of stability and dissociability compatible with storage and subsequent use conditions, but it must also be a functional derivative type compound; that is, it must have an inherent chemical structure which will release acetaldehyde upon decomposition. Also the residual decomposition compound other than the acetaldehyde resulting from the breakdown of the functional derivative compound must not be detrimental to the quality of the finished food product. It is also essential that the breakdown take place under the conditions at which the food product is prepared or used.
Although many attempts, such as U.S. Pat. No. 2,305,621, have been made to produce suitable functional derivative compounds by reacting acetaldehyde with other chemical compounds, with few exceptions, they have not resulted in operational successes. The major causes of the failures have been instability of the resulting product or, conversely, too great a stability to provide utility.
The second method of physically encapsulating the acetaldehyde within a stable compound has not usually met with commercial success since the products prepared by this method have been in a glassy or amorphous state and have tended to lose their fixed flavor during storage especially in the presence of moisture.
A recently issued U.S. Pat. No. 3,314,803 to Dame, et al., discloses a method of fixing acetaldehyde by encapsulating the acetaldehyde in a matrix of dry mannitol. This procedure has produced a dry, non-hygroscopic material which will retain a portion of its fixed acetaldehyde even under non-hermetic conditions, but has the disadvantage of being very costly because of the current price of mannitol. The spray-dried, mannitol-acetaldehyde composition of Dame, et al., can have an initial fixation of 2% to 10% by weight of acetaldehyde. However, this initial fix will be modulated in several days and the level of acetaldehyde will equilibrate to a stable range usually between 1% to 3%.
Generally, the prior art has indicated that in order to preserve flavor materials out of contact with the atmosphere, fixation should be achieved by means of amorphous matrix material. U.S. Pat. No. 2,856,291 to Schultz discloses that crystallization should be avoided since the crystal structure will enable the escape of the flavor materials or the permeation of the atmosphere into the flavoring composition through the interstices of the crystal structure. The Dame, et al., patent discloses encapsulating the acetaldehyde within the mannitol matrix without crystallizing the mannitol.
SUMMARY OF THE INVENTION
According to the instant invention a stable fix for such volatile flavor compounds as acetaldehyde has been achieved by means of crystallizing an edible material such as sucrose from a solution containing the flavor compound. It has been discovered that small amounts of volatile flavoring materials can be fixed in crystalline materials in such a manner that the volatile material will be permanently fixed when stored under hermetic conditions and will retain much of the volatile material even after prolonged storage under non-hermetic conditions.
It is the general object of this invention to produce a moisture-stable flavoring material containing volatile flavoring compounds.
It is a further object of this invention to provide a hon-hygroscopic, solid flavoring composition containing low (less than 1% by weight) amounts of a volatile flavoring compound which composition is capable of being mixed with powdered, fruit flavor mixes and which upon the addition of either hot or cold water during home preparation will enhance the flavor or aroma of a food product.
It is a specific object of this invention to produce a dry, non-hygroscopic, acetaldehyde-containing composition which will retain acetaldehyde under conditions of both elevated temperature and humidity.
It is a more specific object of this invention to fix low (less than 1%) levels of acetaldehyde within the crystals of edible carbohydrate materials such as sucrose and mannitol.
It is a most specific object of this invention to produce a powdered food composition containing a high portion of sucrose and which sucrose has fixed within its crystal structure a low (less than 1%) level of a volatile flavor compound such as acetaldehyde.
DESCRIPTION OF THE INVENTION
This invention is based on the discovery that volatile flavoring compounds such as acetaldehyde can be fixed within crystals of edible materials such as the carbohydrates at levels of less than 0.5% by weight. In the case of acetaldehyde fixed in sucrose, it is normally fixed at a level of from about 0.1% to about 0.2% when an excess of acetaldehyde is employed. It is believed that the volatile compound is fixed as an impurity with the crystals, as the crystals are formed in a mother liquor. This fixation is thought to be akin to what are known as crystal inclusions.
Since the amount of volatile flavor that can be fixed by the method of this invention is relatively low, it is contemplated that the commercial use of this invention would employ a fixing material which is an integral part of a food product. Sucrose is an example of a material which can be employed in this invention and is a normal component of many fruit flavored powdered food products such as gelatin dessert and beverage mixes. The use of such a material as sucrose to also act as a fixing medium for a food flavoring compound such as acetaldehyde will permit the production of an improved food product with very little increase in the cost of raw materials. Sodium chloride is another crystalline material which is often used in large quantities in many foods (e.g., meats) and which can be used to fix volatile flavors (e.g., smoked flavors) according to this invention.
It is also contemplated by this invention that the entrapment of the volatile flavoring compound within sucrose crystals may be accomplished during the crystallization step of the sugar refining operation. This would avoid the necessity of performing a subsequent crystallization operation during the manufacture of the food product.
Another advantage of our invention is that crystalline fixations of acetaldehyde have been found to possess a clean acetaldehyde taste, quite free of the paraldehyde taste. This occurs despite the fact that the acetaldehyde source contains amounts of paraldehyde. It seems that this method of fixation fixes only the acetaldehyde while rejecting paraldehyde.
This invention is especially suited to fix those flavor compounds which are gaseous or which sublime at normal room conditions.
As previously indicated it is believed that the volatile compound is thought to be fixed by means of crystal inclusion. An inclusion may be thought of as foreign matter which is imbedded in the crystal structure and not merely located on the surface of the crystal. The material fixed within the crystals cannot be washed out and tends to remain permanently fixed until the crystal structure is destroyed. It has been found that the volatile flavors fixed in accordance with this invention are in fact unable to be washed out of the crystals and also that the crystalline fixations are able to be heated up to temperatures of at least 100°C without appreciable loss of the volatile compound.
The mechanism by which the volatile flavor compounds are occulded within the crystal structure of fixing material during crystallization is thought to be approximated by a molecular model having a molecule of the flavor compound surrounded by a crystal cage consisting of a plurality of molecules of the fixing material. This mechanism is seen to differ from the inclusion complexes, exemplified by U.S. Pat. No. 3,061,444 to Rogers, et al., where a molecule of the included compound is spatially fitted into a molecule of a cylindrical or spiral shaped dextrin material.
Sugar and sugar derivatives such as sucrose and mannitol are two examples of crystal forming carbohydrate materials that are successful in this invention. Other materials which form the appropriate crystal structure may also be employed in this invention. For instance, successful results can be obtained from crystallizing an aqueous solution of an inorganic salt such as sodium chloride or an organic acid such as fumaric acid with acetaldehyde.
Not all crystal producing materials have been found to produce successful products. Carbohydrates such as dextrose and lactose which form crystal hydrates have been found to fix only very small traces of volatile flavoring compounds, such as acetaldehyde, and are not considered to be acceptable. The reason why these crystal hydrates are unable to fix significant amounts of volatile flavoring compounds is completely understood; however, it is observed that the volatile compounds do not effect the rate of crystallization of such materials. This is in contrast to the formation of anhydrous crystals of sucrose where the volatile compounds are seen to inhibit crystallization and where it is thought that the crystals grow around the foreign material to form crystal inclusions.
The crystallization method used to produce the products of this invention comprises the formation of a super-saturated solution, preferably an aqueous solution, of the crystallizable material. The volatile compound is then added to the supersaturated solution, and crystallization is allowed to proceed. Usually a small amount of seed material is added to the supersaturated solution in order to initiate crystallization. The crystals thus obtained are separated and dried.
The crystallization step may also proceed under vacuum conditions where surprisingly it has been found that the fixation levels of such volatile compounds as acetaldehyde is equal to or better than the fix levels under atmospheric processing. In practice a vacuum crystallization step would be highly desirable since the crystallization time would be shortened and since a large portion of the water will be removed under the vacuum conditions.
A preferred, or best mode, for carrying out the method of the present invention is disclosed in the copending application of William A. Mitchell, Ser. No. 376,088, filed July 2, 1973. The disclosure of that application relates to carrying out the crystallization from a supercooled, glassy, aqueous solution containing the volatile flavoring compound and from 88% to 93% sucrose based on the combined weight of the sucrose and water. Crystallization in this manner proceeds rapidly to form a stiff, crumbly mass of product which can be efficiently dried. The disclosure of that application is hereby incorporated by reference; however, the details thereof form no part of the present invention.
The present invention is further illustrated by, but not limited to, the following examples:
EXAMPLE I
A sucrose-water mixture of 539 grams of sucrose and 161 grams of water were heated until all of the sucrose dissolved. The solution was then cooled to below the boiling point of acetaldehyde (21°C), or as in this case to 10°C, producing a super saturated solution of sucrose. Twenty-one milliliters of acetaldehyde (16.5 grams) were added slowly with stirring. One gram of powdered sucrose was added to initiate crystallization. The mixture was allowed to crystallize for 2 days although less time may have been adequate.
After crystallization was complete, the mixture appeared white and seemed to have dropped in viscosity. Crystals could be felt in the syrup. The mixture was added to the basket of an International Chemical Centrifuge Model 367-H which was spinning at high speed. The crystals were retained by the basket while the syrup passed through. The filter cake was removed from the basket and powdered by passing through a No. 30 U.S. mesh screen. The crystals were allowed to dry over night. This procedure yielded 200 grams of crystalline sucrose or 37.1% of the starting material. These crystals were analyzed by a polarographic procedure and found to contain 0.135% acetaldehyde. Organoleptically, the sucrose was found to have a clean acetaldehyde taste even though the original acetaldehyde contained significant amounts of paraldehyde and did not have a clean taste.
The syrup obtained by centrifugation was saturated with sucrose and contained significant amounts of acetaldehyde. Additional sucrose may be added to the syrup and the mixture heated to obtain a solution of approximately 72% sucrose. Upon cooling the solution to below 21°C additional acetaldehyde is added to produce a solution of approximately 2.3% acetaldehyde. The crystallization and centrifugation procedures are similar to those given above. In this manner, the total process may be considered cyclic and almost 100 % efficient.
EXAMPLE II
Ten grams of mannitol were dissolved in 55 ml water at room temperature. To this solution were added 1.9 ml acetaldehyde. Thirty grams of mannitol were dissolved in 30 ml water by heating. This solution was added to the solution containing acetaldehyde. The total solution now consisted of 40 grams of mannitol, 85 ml water, and 1.9 ml acetaldehyde. Upon cooling the solution began to get viscious and milky in appearance. After about an hour and a half, crystallization was completed. The mannitol crystals were filtered and air dried. Organoleptically, the mannitol was found to have a clean acetaldehyde taste. The material was analyzed and found to contain about 0.16% acetaldehyde.
EXAMPLE III
Ten grams of mannitol were dissolved in 55 ml of water at room temperature. To this solution was added 19 ml of acetaldehyde. Fifty grams of mannitol were then dissolved in 50 ml of water by heating. The two solutions were then combined and placed in a vacuum desiccator where a vacuum of 150 mm of Hg. was quickly achieved. After most of the water had been removed (about 60 minutes), the mannitol crystals were removed from the desiccator and air dried. The fix level of acetaldehyde was found to be 0.48%.
The material of Example I containing 0.135% acetaldehyde was evaluated for stability by packaging 7 grams of the sucrose fixed acetaldehyde (containing about 9.45 mg of acetaldehyde) together with 85 grams of a standard-type gelatin dessert having a composition of:
Ingredients Parts by Weight______________________________________Sugar 80.0Gelatin 10.0Citric Acid 3.0Trisodium Citrate 1.2Fruit Flavor 0.6Fruit Color 0.2______________________________________
The packages were wax-paper polyethylene laminate pouches which are heat sealed and placed into small paper containers. Individual packages were stored at 90°F/85% RH or 90°F/70% RH and periodically removed and analyzed for acetaldehyde using a polarograph.
TABLE______________________________________R.H. at 90°F Days Storage % Loss of Acetaldehyde______________________________________70% 8 085% 8 070% 42 285% 42 770% 120 4685% 120 42______________________________________
The stability data is quantitatively only an approximation since due to imperfect blending not all samples analyzed are identical to the composition of the overall package. Qualitatively, however, both 8-day samples were found to be free flowing with no signs of caking and to have a clean acetaldehyde taste. The 42-day sample stored at 85% R.H. was somewhat caked but had a clean acetaldehyde taste; whereas, the 70% R.H. sample showed only slight signs of caking and possessed a clean acetaldehyde taste.
Evaluation of additional anhydrous crystalline material has shown that organic crystals such as fumaric acid and inorganic crystals such as sodium chloride are able to fix low levels (less than 1%) of clean acetaldehyde. Additionally, such volatile flavoring substances such as maltol, and natural and synthetic roasted coffee aromas (e.g. synthetic grinder gas and the like) have been successfully fixed within sucrose crystals.
The process of the present invention can be employed to tenaciously fix volatile flavoring compounds within individual crystals of crystallizable materials at levels up to a maximum of about 0.5%. In the case of acetaldehyde fixed in sucrose, a fix at a level of about 0.1% to 0.2% is easily achieved using an excess of acetaldehyde during crystallization. When employed in dry beverage or dessert mixes it is usually desirable to use crystalline sucrose prepared according to the present invention which contains the volatile flavoring compound fixed therein at about the 0.1% to 0.2% level. However, for other applications, such as an acetaldehyde-containing sugar for sprinkling on and enhancing the flavor of foodstuffs such as fruits (e.g. strawberries, peaches, raspberries, etc.), relatively low amounts, e.g. on the order of 0.001% to 0.1%, of acetaldehyde may be desirable. Other levels, e.g. below 0.001%, and above 0.2%, are of course suitable to a varying extent for these and other uses.
It will be apparent that there are variations and modifications of this invention, and that the examples and typical operating conditions may be varied without departing from the scope of the invention. | Volatile flavoring compounds such as acetaldehyde are fixed in low amounts by having the compound present in solution during the crystallization of sucrose. It is believed that the volatile flavors are entrapped as impurities within the crystal structure. The resulting compositions have excellent stability over a wide range of humidities, are soluble in both hot and cold water, and have application as flavor and aroma modifiers for foods. | 0 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a process for the production of a pectin preparation, and particularly of fruit pectin, e.g., apple pectin, which is suitable for the production of jellies with a particularly low solids content.
2. Description of the Prior Art
Highly esterified pectins form jelly, in which the gel formation is based on a dehydration and electrical neutralization of colloidally dispersed and hydrated pectin agglomerates. In addition, sugar or a sugar substitute material must be present as a dehydration agent at a concentration of almost 65%, and the required pH value must be maintained within a narrow tolerance range. The individual pectin molecules are, at the same time, linked by hydrogen bonds, which are formed with the sugar.
Partially esterified pectins, i.e., pectins with a degree of esterification less than 50%, have gelling or thickening properties which are similar to those of agar or gelatin. Partially esterified pectins are used in the food industry, for example, for the production of low solids jellies, milk puddings and sugar-free jellies.
The gelling property of partially esterified pectins depends upon the amount of pectin, the solid content, the pH value and the buffer salt content and on the amount of calcium ion present. Moreover, the calcium ion concentration plays a significant role in which the optimum amount of calcium ion changes as a function of the degree of esterification. The optimum calcium content, expressed in mg Ca/g of pectin, which forms a solid gel, is a defined quantity for a particular pectin. If this calcium concentration is exceeded, a brittle gel results with a strong tendency towards syneresis. At the same time, the dependence on the pH value and the solids content plays only a subordinate role. For the technological application of these pectins, the following factors are, however, unfavorable:
1. THE LOWER THE DEGREE OF ESTERIFICATION OF A PECTIN, THE LESS IS ITS SOLUBILITY IN WATER;
2. FOR MAINTAINING AN OPTIMUM CALCIUM ION CONCENTRATION, AN ADDITION OF CALCIUM IS USUALLY NECESSARY. This addition depends on the water used and on the fruit.
SUMMARY OF THE INVENTION
We have discovered a method for making a pectin preparation on the basis of partially esterified pectin with an amount of calcium that is optimum for its degree of esterifications in a manner that a sufficient amount of buffer salt is simultaneously present in order to keep this pectin in aqueous solution.
It is noted that when referring to calcium herein, it is also considered to be representative of other comparable materials, such as, for example, magnesium or the like.
More particularly, the inventive process comprises the following steps:
a. a pectin is used as a starting material, which has a metal binding power of 30 to 140 g of metal salt, calculated as CaCl 2 , per kg of pectin with a degree of esterification of 30 to 40%, preferably 35 to 38%,
b. at a temperature between 10° and 90° C., a solution is prepared from this pectin, water and a phosphate selected from the group consisting of orthophosphates, pyrophosphates, and polyphosphates, and preferably sodium pyrophosphate, so that a pH value between 4.4 and 4.8 is obtained,
c. a certain amount of soluble calcium, magnesium, aluminum or iron salts or mixtures of these salts are added in dry or dissolved form to the solution with stirring, the amount corresponding stoichiometrically to an amount of 30 to 140 g or CaCl 2 /kg of pectin, and
d. the pectin preparation thus formed is precipitated from the solution and dried.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
As phosphate, orthophosphates, polyphosphates, and pyrophosphates, such as sodium phosphate, and preferably tetrasodium pyrophosphate, are suitable for use.
By using the inventive process, a pectin preparation can be obtained by reacting partially esterified pectin with certain phosphates under given reaction conditions and at a given pH value. The prepared pectin phosphate compound is caused to react with calcium iron, whereby, after precipitation, a phosphated Ca-pectin is obtained which may be described as calcium phospho-pectin. It may be assumed that in this calcium phospho-pectin, the greater portion of the calcium is not bound directly to pectin but rather, is linked via the phosphate group with the pectin.
In technical applications, the calcium phospho-pectin produced with the process of the present invention exhibits the following advantageous properties.
The solubility in cold and warm water is good and it forms a solution of relatively low viscosity, which is easy to work with. On adjusting the pH to a certain value during the cooking, the calcium phosphate group splits off from the pectin. At the same time, the original partially esterified pectin is reformed and is then present in a defined concentration of calcium and buffer. Moreover, the reaction of pectin with calcium takes place slowly and a uniform calcium pectinate gel is formed. Although there continues to be a dependence on the pH value, the pH range may be significantly greater than in the case of highly esterified pectins. The calcium sensitivity, i.e., the dependence on the fruit or the surrounding medium, is slight. The inventively produced pectin preparation is similar to amidized pectin in regard to the calcium and pH dependence. However, in the case of the inventive calcium phospho-pectin, the optimum amount of calcium is already incorporated therein.
The following example illustrates the present invention:
A partially esterified pectin, with a degree of esterification of 30 to 40%, especially of 35 to 38%, is used as the starting pectin.
Determination of Amount of Calcium to be Added
In order to determine the necessary calcium chloride requirement, cooks are prepared with increasing amounts of calcium chloride. The following formulation is used as basic cook (example):
500 g Strawberry pulp
500 g Partially esterified pectin solution, 2.5% concentration (= 12.5 pectin)
650 g Fructose syrup, 70% concentration
ca. 3 ml of 50% citric acid for adjusting the pH value to 2.9.
By cooking to a solid content of 50%, a 1 kg cook is obtained.
Increasing amounts of a 2% CaCl 2 solution are added to 100 g samples of this cook. The calcium chloride solution is stirred into this cook immediately after it is poured out and while it is still very hot. These samples are set aside to cool and gel.
As a rule, an addition of ca. 2 to 7 ml of CaCl 2 solution is adequate. A 2% solution of anhydrous CaCl 2 is used. The consistency of the cook was used as a measure of the amount of CaCl 2 required. In the series of increasing strength, the sample with the best gel strength, immediately preceding the sample which begins to be gritty, was evaluated in the calculation. In so doing, an addition of each 1 ml CaCl 2 solution (2%) to 100 g of the cook containing 1.2% of partially esterified pectin, corresponds to a later dosage of 16.67 g of CaCl 2 (anhydrous)/kg of pectin. A calcium dosage of 6 ml to 100 g of cook corresponds, for example, to a later weighed-in quantity of 100 g of CaCl 2 for each 1 kg of partially esterified pectin.
A 30 kg Charge of Pectin Was Used as Example
A receptacle was filled with 1,200 l of water at a temperature of 50° to 60° C. Into this water, 30 kg of the above defined starting pectin were weighed-in while stirring rapidly. Subsequently, 16.0 kg of tetrasodium pyrophosphate decahydrate (Na 4 P 2 O 7 .10H 2 O) in solid form were added in order to obtain a pH value of 4.4 to 4.8 in the solution. After the addition of pyrophosphate, stirring was continued for about a further 15 minutes at a reduced speed, until the pectin was completely dissolved.
The dosage of sodium pyrophosphate should not be higher at this time, since reactions could occur which might have an undesirable effect on the final quality. Alternatively, the possibility exists of adding the sodium pyrophosphate first to the water and then the pectin or of adding both materials together.
Subsequently, the calculated amount of food-grade quality CaCl 2 with a degree of purity of 96% is added in the form of a 10% solution, preferably through an injector, while stirring rapidly. Intensive stirring is necessary in order to achieve a rapid and good distribution of CaCl 2 . After addition of the CaCl 2 , rapid stirring must be continued for a period (generally about 5 minutes), in order to ensure an optimum reaction.
The CaCl 2 addition should be carried out in such a manner, that pectinate formation is avoided. In place of calcium chloride, other soluble calcium salts and/or magnesium salts, aluminum or iron salts or mixtures of these may also be added. On the whole, salts of multivalent metal ions may be added which meet the requirements for food-grade additives.
A further amount of pyrophosphate is added subsequently. This amount is determined by testing a sample in the laboratory for its pH value and its viscosity. The pH value should be adjusted to 5.0 ± 0.2. The viscosity is, however, a better criteria and viscosities between 30 to 35 cP at 20° C. (measured at 2,770 sec -1 ) are acceptable). Higher viscosities should not be accepted. Viscosity measurements were carried out on a Rotovisco at n = 512 rpm with decreasing frequency of rotation, 100 S calibration with NV measuring equipment. Stirring is also rapid during this addition of pyrophosphate, which is in solid form.
After this amount of pyrophosphate has been dissolved, the pH value and viscosity of the solution are checked once again.
Possible corrections can be carried out even after these stop. Since all of these measurements are carried out on a solution of 30 kg of partially esterified pectin in 1,200 l of water (= 2.5%), other test data must be used as a basis when working with solutions of different concentration. Viscosity and pH value measurements will then be redefined.
Accordingly, it is possible to work with higher concentrations of pectin for which, for example, 30 kg of pectin may be mixed into 700 to 800 l water. For the subsequent precipitation, it is advantageous to select a concentration higher than 2.5%, for example, a 5% pectin solution.
If the laboratory finding for the solution of the pectin preparation is positive, the solution is precipitated by the well-known procedure in alcohol.
After the precipitation is completed, the precipitation is squeezed-out using an extrusion press.
The squeezed-out pectin preparation is dried in a stream of air heated to not more than 60° C. Subsequently, the preparation is ground in the usual manner.
The calcium phospho-pectin thus obtained has the advantageous properties described hereinabove.
In addition, experiments were carried out in order to test the dependence of gelling on the initial pH value of the pectin preparation. In so doing, it has turned out that, for a pH value of ca. 5.0, gelling is best for the defined CaCl 2 content. If the 2.5% solution of pectin preparation has a pH value greater than 5.0, the gelling power of the sample cook becomes worse with increasing pH value of the initial solution. The pH value in the sample cook is constant hetween 2.9 and 3.0. This experiment is intended to show that the gelling ability decreases at pH value above 5.0 in the pectin solution. The viscosity of solutions with a pH value of 5.0 is very low. In any case, a low pH value or a high viscosity of the solution is of advantage, since the deposition of calcium takes place less readily. A sufficient phosphating of the preparation nevertheless remains ensured.
When using most of the gelling agents presently commercially available, for example, for the preparation of milk or fruit desserts, it is necessary to dissolve the gelling agent with boiling in water and/or possibly to prepare the gelling agent for gel formation by the addition of, for example, citric acid or the like.
it is therefore a further object of the invention to provide a food-grade gelling agent, which may be used directly as a solid gelling agent without any preliminary preparative steps.
In order to accomplish this purpose, the present process for the production of a food-grade gelling agent comprises bringing 1 to 4 weight percent of a calcium phospho-pectin on the basis of pectin, prepared as above, and especially apple pectin, into solution with stirring in 20 to 80 weight percent of water. In this solution, 20 to 80 weight percent of a filler, on the basis of sugar or sugar substitute materials, are subsequently dissolved.
Thus, in the gelling agent of the present invention, 20 to 80 weight percent of a filler, on the basis of sugar or sugar substitute materials, are added to this solution.
Based on the excellent gelling ability of the above described pectin preparation (referred to as NV-50 in the following), which represents a calcium phospho-pectin obtained from fruit pectin, a process has been developed which permits a food-grade jelly to be produced in a simple manner by mixing the inventive gelling agent at normal temperatures with approximately an equal volume of fruits (fresh, frozen or from cans), fruit juices, milk, milk products and sour milk products. The inventive food-grade gelling agent is prepared as follows:
1 to 4% of NV-50 are brought into solution in water and the solution is brought to a solids content of 20 to 80% by additionally dissolving a filler.
As a filler, sugars and sugar substitute materials, such as, for example, sucrose, invert sugar, sorbitol, fructose, xylitol, starch syrup, etc., are suitable. In both the production and the processing of the liquid gelling material, one can operate without the addition of acids or calcium salts, the natural acid or calcium iron content of the foods used being sufficient for gelling.
At the same time, attention must be paid to maintaining a solids content that delays or avoids the perishability of the product and/or maintain sterile working conditions (sterile filling at temperatures higher than 70° C.) and/or to assuming that the solution is preserved by additives.
As example of the preparation of the liquid jelly (that is to be poured) or of the gelling agent is as follows: For a 2% solution of NV-50 in a 50% solids solution with sugar using hot filling, 2 kg pectin NV-50 are added to 50 kg water at a temperature of 40° to 100° C. with rapid stirring. Stirring must be continued for a brief time until the pectin is fully dissolved. To this solution, 40 kg of sugar are added with further stirring until the sugar is completely dissolved. Subsequently, the product is bottled while maintaining the above-mentioned conditions to avoid microbial spoilage. The pH value of the liquid jelly, prepared according to this process, must be between 3.8 and 5.2 before pouring, so that gelling of the liquid jelly is prevented.
If necessary, the pH must be corrected by the addition of appropriate additives. In the above example, a pH value of 4.8 proved to be most favorable (adjustment was made with tetrasodium pyrophosphate).
The following possibilities are mentioned as examples of use:
Preparation of a Milk Dessert or of a Sour Milk Dessert
To a selected volume of pourable liquid jelly (100 ml.) approximately the same volume (50 to 200 ml.) of fresh milk, H-milk or a sour milk product available in the market, such as, curds or yogurt, are stirred in and allowed to stand for a brief period for the development of the final consistency.
Fruit Dessert
To a selected volume (100 ml.) of pourable liquid jelly, approximately the same volume (50 to 200 ml.) of prepared fresh fruit (strained or in small pieces), defrosted frozen fruit, fruit from cans or fruit juices of any kind are added with stirring and allowed to stand for a brief period for the development of the final consistency.
The fruity taste of the dessert may be improved by the addition of a certain amount of fruit acid or citric acid to the fruit or the fruit juice. At the same time, however, care must be taken that this does not cause a more rapid gelling or an increase in the gel strength.
Preparation of Jelly Material and Jelly Topping for Fancy Cakes
The preparation proceeds in the same manner as for the described fruit desserts. After stirring in the pourable liquid jelly into the fruit or into the juice, the material, before it gels, is distributed over the cake layer or poured on after the take-off process. | A method for the production of a pectin preparation wherein fruit pectin having a metal binding power of 30 to 140 g of metal salt is dissolved with a phosphate to produce a solution having a pH between 4.4 to 4.8 and wherein the soluble metal salt is added to the solution in a stoichiometric amount of 30 to 140 g calculated as calcium chloride per kg of pectin and then precipitating the pectin from the solution. The preparation thus prepared has good solubility in cold and warm water and forms a low viscosity solution which is easy to work with. The nature of the preparation as well as gelling agents prepared therefrom are disclosed. | 0 |
FIELD OF THE INVENTION
This invention relates to a sealing mat for multiwell laboratory plates. The invention also relates to a lid for a multiwell laboratory plate which includes a sealing mat and to a method of sealing a multiwell laboratory plate using those things.
BACKGROUND TO THE INVENTION
Multiwell plates are used extensively in molecular biology laboratories and elsewhere. One such use is in Polymerase Chain Reaction (PCR) experiments where, once filled or part filled with reagents, the plates are often sealed prior to further processing.
Multiwell plates now come in a variety of formats. 96 wells, in a 12×8 array, is one standard but now a 384 well format is becoming increasingly common. Forming a cheap, re-usable seal on these 384 plates presents a real problem.
There are a number of known ways of achieving such seals. For example, a foil or plastic film may be applied across the entire upper surface of the plate. Thus heat sealable aluminium foils or adhesive plastic films are commercially available. Once applied, these films provide an efficient, gas and liquid tight seal but are tiresome to apply and remove. Access to each well can only be obtained by piercing the film or by peeling the film off by hand or with a foil stripper. Consequently, this type of seal is not re-usable, and is not suitable for robotic application or removal.
Alternatively, a seal may be achieved by placing a relatively heavy, flexible rubber mat over the entire surface of the plate. The weight of the mat and any plates stacked on top of the mat keep the seal in place. It is important that the mat does not slide over the top of the plate in order to avoid cross-contamination. In the case of 96 well plates, this is achieved by having 96 raised pimples or “dimples” on the surface of the mat in an array which matches exactly the array of wells. Each dimple is sized and shaped to sit firmly into a well. Once in place, no lateral movement of the mat is possible because the perimeter of each dimple fits snugly within its respective well.
This arrangement is not applicable to the 384 well version because the wells are much smaller in diameter. Each dimple would need to be so small in profile that it becomes very difficult to align the mat with the wells. Even if the mat can be aligned, there is an increased tendency for the mat to slide across the top face of the wells because each dimple is correspondingly smaller than in the 96 well version.
As a further alternative, sealing caps can be applied, either in strips or as an array of 96. These sealing caps consist of individual, circular cylindrical walled caps with a pierceable lid. They fit snugly into the internal bore of each plate and each cap normally has an outer lip, which prevents it entering into the well beyond a certain point.
These caps are time-consuming to apply and require a good deal of manual dexterity on the part of the technician. Furthermore, sealing caps would be practically impossible to fit to 384 well plates, and, in any event, cannot be inserted or removed robotically.
It is therefore an objective of the present invention to overcome some or all of these disadvantages and provide an improved, re-usable sealing means applicable to all multiwell plates.
SUMMARY OF THE INVENTION
According to the present invention, there is provided a plate sealing means or cover suitable for use with multiwell plates of the type in question said sealing means comprising:
(i) a resilient sealing mat having a flat or even surface substantially free from dimples; and
(ii) engagement means adapted to co-operate with at least two opposing edges of the plate and adapted to retain the sealing mat in a substantially fixed position with respect to the plate. By providing some means of engaging the mat with the side of the multiwell plate it is no longer necessary to use dimples as locators.
Preferably, the engagement means comprises a lid adapted to fit over the plate, said lid comprising a substantially flat top with depending edges, the sealing mat being located on the underside of the lid top, being the side in contact with the plate when the sealing means is in use. This provides the advantage that a multiwell laboratory plate can be quickly and effectively sealed by placing the lid onto the plate. Also, the lid can quickly and easily be removed and can be re-used. It is not necessary to accurately position any projections on the mat into wells on the multiwell plate because the mat is smooth on the surface which contacts the multiwell plate.
Preferably, the lid is substantially rigid.
In a particularly preferred embodiment, the lid further comprises locators on its uppermost-in-use surface, said locators being adapted to locate with the underside of a second plate such that the plates will stack securely one on top of each other.
Preferably, the edge of the lid incorporates apertures corresponding with holes in the plate, said holes being provided to facilitate robotic plate positioning and removal from a thermal cycle block. Robotic operation is particularly important when large numbers of plates have to be handled. The plates must still be capable of robotic manipulation even when the lids are in place.
In an alternative embodiment, the engagement means comprises a series of lugs projecting from the sealing mat and adapted to engage with holes in the plate, said holes being provided to facilitate robotic plate positioning and removal from a thermal cycler block.
Preferably the lugs are resiliently flexible.
Preferably the lugs project outwardly from the edges of the mat in the plane of the mat.
In a particularly preferred embodiment the sealing mat and the lugs are of unitary construction.
Preferably the sealing mat is made from neoprene or silicone rubber.
In order that the invention may be better understood, preferred embodiments will now be described, by way of example only, with reference to the accompanying schematic drawings, in which:
FIG. 1 illustrates a plan view from above of a lid for a multiwell plate according to a first embodiment of the invention;
FIG. 2A shows a cross-section along line A—A of FIG. 1;
FIG. 2B is an enlargement of a detail in FIG. 2A;
FIG. 3 shows a plan view from below of the lid of FIG. 1;
FIG. 4A shows a cross-sectional view along line B—B of FIG. 1;
FIG. 4B is an enlargement of a detail in FIG. 4A;
FIGS. 5A, 5 B and 5 C illustrate plan, side and end elevations of a sealing mat according to a second aspect of the invention;
FIGS. 6A, 6 B and 6 C illustrate plan, side and end elevations of a lug from FIG. 5;
FIG. 7A shows diagrammatically the location of robotic arm locator holes;
FIG. 7B shows how the lugs of this embodiment flex over to locate in the robotic arm locator holes.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Preferred embodiments of the present invention will now be more particularly described by way of example only. These are currently the best ways known to the Applicant of putting the invention into practice, but they are not the only ways in which this can be achieved.
FIG. 1 illustrates a plan view from above of a sealing means 20 for a multiwell plate. The sealing means or cover consists of a substantially rectangular lid 1 with dependent edges 7 into which is fitted a sealing mat 4 . The dependent edges retain the sealing mat in place over a plate. One corner of the lid has a chamfered corner 2 which acts as an orientation marker and is adapted to fit a correspondingly shaped cut-away on the corner of a PCR plate. The dimensions of the chamfered corner 2 are dictated in part by the dimensions of the plate.
The lower or inner surface of the lid 1 is substantially flat or planar and the lower surface of the sealing mat 4 is also correspondingly flat and smooth. This is an important feature of the present invention because it avoids the need for any dimples to locate in the wells.
The top of lid 1 may incorporate projections or recesses 3 which act as locators for the bottom of another plate. Thus, in the case of a skirted plate, the projections take the form of rims 3 at each corner of the lid into which the skirt of another plate will fit. This is illustrated more clearly in FIGS. 2A and 2B. Once again, the rim at one corner is angled to correspond with a cut-away on the plate.
Once a multiwell plate is sealed with a lid 20 then several other lidded plates can be stacked one or top of each other using the locators to hold the stack in place.
It is not necessary for the rim to be continuous around the perimeter of the lid although this is possible.
If the plates are not skirted then some other form of projection or indentation can be provided to retain the bottom of the outer walls of the plate above. This disclosure is intended to encompass any suitable locator adapted for this purpose.
The edges of the lid are an important feature of this invention. Not only do they retain the cover in a snug positional fit with the plate beneath, but they also provide access for robotic arms, which typically manipulate these plates. Thus, in at least two of the sides 6 of the lid, gaps or apertures 9 are provided to enable the covered plate to be picked up by a robotically controlled lifting apparatus as is known in the art. These gaps 9 in the sides 6 of the lid correspond with holes in the side of a multiwell laboratory plate so that in use, when the lid is in place, it is still possible to insert the fingers of a robotically controlled arm into these holes. The apertures 9 are large enough to enable the lid to be used with a variety of different multiwell laboratory plates from different manufacturers, which inevitably have holes in a slightly different location.
FIG. 2A is a cross-section along line A—A of FIG. 1 and shows how a sealing mat 4 is fixed to the underside of the lid. In this example, the sealing mat is made from neoprene rubber although any other suitable material as selected by the materials specialist, such as silicone rubber, can be used. The lid 1 has sides 6 , 7 which extend in use over the rim of the multiwell plate (not shown). The sealing mat 4 can be fixed to the underside of the lid in any suitable manner, for example, using glue or other adhesive.
FIG. 3 is a plan view from below of the lid of FIG. 1 . This shows the sealing mat 4 on the underside of the lid.
FIG. 4A is a cross-section along the line B—B of FIG. 1, and also shows the locator projections 3 . In this example the sealing mat is located by lugs 5 on the underside of the lid. These lugs make it easier to locate the mat in the correct position during assembly. They also ensure that the mat is fixed centrally over the plate.
FIG. 4B shows one of the lugs 5 in more detail on the underside of the lid which retain the mat 4 in place and ensure that it is fixed into the correct position inside the lid. Once the sealing mat 4 is fixed to the underside of the lid, then the cover 20 can simply be placed onto a multiwell plate in order to seal the plate. It is not necessary for the mat 4 to incorporate any dimples for locating into the tops of the wells in the plate and this makes it easier to position the lid and mat in place. Also, the mat 4 cannot slip or move about on the plate because it is held in place by the lid, which has sides 6 , 7 that locate around the rim of the multiwell plate. This avoids any possible cross-contamination of the contents of adjacent wells.
The terms sides or edges in this context have a very broad meaning. The terms are intended to encompass any form of restraint which keeps the cover in place when it is over a multiwell plate. It is certainly not necessary that the sides or edges should extend around substantially the whole of the lid although this may be desirable.
It will be appreciated that the combination of the lid 1 and the sealing mat 4 comprises a sealing means for sealing such plates. The edges of the lid act as an engagement means, which co-operates with at least two opposing edges of a multiwell plate to retain the sealing mat in a substantially fixed position with respect to the plate itself. The sealing mat is made of any suitable resilient material, which enables it to deform around the mouth of each well and thus form an effective seal.
A further embodiment 30 of the present invention is illustrated in FIGS. 5A-5C and 6 A- 6 C. A resiliently flexible sealing mat 24 is provided with projections or lugs 28 which are so sized and shaped as to fit into some of the robotic location holes in a skirted multiwell plate. At least one corner 30 of the sealing mat 24 is chamfered in order to assist in the orientation of the mat 24 . This type of sealing mat 24 is used together with a multiwell laboratory plate of the type with robotic handling holes as illustrated in FIG. 7 A. FIG. 7A is a schematic plan view of a multiwell laboratory plate 11 , which has at least eight robotic locator holes in its sides. The position of these robotic locator holes is indicated by the arrows.
The sealing mat 24 and lugs 28 are preferablyy of unitary construction being formed from a single piece of resiliently flexible material such as neoprene or silicone rubber. In use, the projections 28 are bent over the rim of the multiwell plate 11 and inserted into four of the robotic locator holes in the sides of the skirt of the plate. The projections each have a head 22 as shown in FIGS. 6A-6C. These heads are slightly larger than the robotic locator holes. However, because the projections 28 are made of flexible, resiliently deformable material, the heads can be squeezed through the robotic locator holes. This secures the mat 24 to the multiwell laboratory plate 11 and creates an effective seal. Other multiwell laboratory plates that have been sealed in this way can be stacked one on top of each other. The sealing mats 24 are preferably made from rubber or other suitable material which has a non-slip surface which helps to prevent the plates in a stack moving in respect to one another.
The shape and configuration of the lugs are an important feature of this invention. The head of each lug is spaced from the body of the mat by a neck 27 . The lug has a head region 22 , which is generally thicker than the body of the mat to which it is attached. A retaining section 26 creates what is, in effect, a resiliently flexible headed stud with an undercut waist region 25 . This arrangement is so sized and shaped that the retaining section 26 will just pass through the robotic locator holes in the skirt of the plate but will not immediately slip back. The sealing mat is therefore retaining in sealing contact with the plates until the retaining section 26 is resiliently deformed to withdraw it from the hole.
It will thus be appreciated that the lugs from an engagement means adapted to co-operate with at least two opposing edges of the plate to which the sealing cover is to be attached and which are adapted to retain the sealing mat in a substantially fixed position with respect to the plate.
The covers of the present invention can be formed from a wide variety of materials as selected by the material specialist. For example, the lids can be formed from any suitable substantially rigid plastics material such as polyethylene, polypropylene, polyvinylchloride, polystyrene or polycarbonate. Neoprene or silicone rubbers are suitable materials for use in the sealing mat. | A plate sealing means suitable for use with multi-well plates of the type used in DNA PCR chemistry, said sealing means having a resilient mat having a flat or even surface substantially free from dimples; and an engagement structure adapted to co-operate with at least two opposing edges of the plate and adapted to retain the sealing mat in a substantially fixed position with respect to the plate. | 1 |
[0001] This application is a continuation of International PCT application no. PCT/FR00/00163, filed on Jan. 25, 2000, which designated the United States.
FIELD OF THE INVENTION
[0002] The invention relates to a multi-enzyme product with glucoamylase, proteolytic and xylanase activities and a method for producing same by solid state fermentation of wheat bran with Aspergillus niger.
BACKGROUND OF THE INVENTION
[0003] It is known to produce ethanol from corn starch by an enzymatic method comprising a stage for liquefying the starch with an alpha-amylase for hydrolyzing the starch to dextrins, and then a saccharification stage by a glucoamylase (also called amyloglucosidase) for hydrolyzing the dextrins to glucose, and finally a stage for fermenting the latter to ethanol.
[0004] The use of alpha-amylase and glucoamylase enzymes is generally satisfactory when relatively pure starch milk, obtained by the wet milling of corn, is used as starting material, but when it is desired to substitute wheat starches or wheat flours for corn starch, no satisfactory results are obtained with these two enzymes alone because of the presence of hemicelluloses, which increase the viscosity of the saccharified flour worts to the extent that this creates a problem for carrying out the method. It is necessary to use, at the saccharification stage, auxiliary enzymes such as cellulases and hemicellulases in order to reduce the viscosity and remedy this problem. Moreover, it is desirable also to use proteases during saccharification so as to hydrolyze the proteins in the flour and thus enrich the wort with soluble nitrogen in anticipation of the subsequent alcoholic fermentation stage. The traditional supply of nitrogen source necessary for the growth of yeasts during this fermentation may thus be reduced.
[0005] All these enzymes are individually commercially available in purified form, but have the disadvantage of being relatively expensive and therefore of increasing the cost of producing ethanol from wheat. In addition, compositions have to be formulated from individual enzymes, which complicates the method.
[0006] A need therefore exists for an inexpensive multi-enzyme product combining glucoamylase, proteolytic and hemicellulase activities to produce ethanol from wheat flours at a low cost.
[0007] The invention aims to satisfy this need.
SUMMARY OF THE INVENTION
[0008] The present invention relates to a multi-enzyme product exhibiting glucoamylase, proteolytic and xylanase activities, characterized in that it consists of wheat bran fermented with an Aspergillus niger strain, said enzymatic glucoamylase, proteolytic and xylanase activities being present at the following minimum values:
[0009] glucoamylase: at least 100 GU per gram of dry matter,
[0010] proteolytic: at least 100 PU per gram of dry matter,
[0011] xylanase: at least 100 XU per gram of dry matter, provided that at least one of the following conditions is satisfied:
[0012] the glucoamylase activity is at least 750 GU per gram of dry matter
[0013] the xylanase activity is at least 300 XU per gram of dry matter.
[0014] The glucoamylase activity is preferably at least 1 500 GU per gram of dry matter and/or the xylanase activity is at least 400 XU per gram of dry matter.
[0015] Also, the proteolytic activity is preferably at least 400 PU per gram of dry matter.
[0016] The invention also relates to a method of producing this multi-enzyme product, characterized in that it comprises the stages consisting in (a) taking wheat bran; (b) moistening and heat-treating said bran so as to pasteurize it or sterilize it; (c) inoculating the resulting wheat bran with an Aspergillus niger strain; (d) the bran being in the form of a layer at least 10 cm thick, fermenting it in the solid state in a reactor which is aerated and stirred periodically for a period of 1 to 3 days, at a temperature of 28-38° C., preferably 32 to 36° C., said bran being adjusted to an initial moisture content of 50 to 60 wt. % which is substantially maintained during the duration of the fermentation, under aeration conditions appropriate for avoiding accumulation of carbon dioxide which is harmful to the fermentation in the reactor and a rise in temperature due to fermentation above the recommended range, until the fermentation product exhibits the following minimum enzyme activity values:
[0017] glucoamylase: at least 100 GU per gram of dry matter,
[0018] proteolytic: at least 100 PU per gram of dry matter,
[0019] xylanase: at least 100 XU per gram of dry matter, provided that at least one of the following conditions is satisfied:
[0020] the glucoamylase activity is at least 750 GU per gram of dry matter
[0021] the xylanase activity is at least 300 XU per gram of dry matter.
[0022] The glucoamylase activity is preferably at least 1 500 GU per gram of dry matter and/or the xylanase activity is at least 400 XU per gram of dry matter.
[0023] Also, the proteolytic activity is preferably at least 400 PU per gram of dry matter.
[0024] The Aspergillus niger strain is preferably chosen from the NRRL 3112 strain, the ATCC 76061 strain and the strains obtained from said strains by selection or mutation when a high glucoamylase activity is desired. The ATCC 76061 strain is particularly preferred.
DETAILED DESCRIPTION
[0025] When a high glucoamylase activity is desired, the wheat bran used as starting material should be a non-starch-free bran. Apart from this restriction, any bran may be used. However, the bran preferably comprises a significant proportion (at least 40 wt. %) of particles of less than 1 mm.
[0026] The characteristics of two suitable brans are given below by way of illustration.
Bran A Bran B Characteristics Moisture (%) 12.3 19.5 Protein content (% WM*) 13.8 14.8 Starch content (% WM*) 24.6 21.3 Particle size >1.25 mm 53.9 0.7 from 1.0 to 1.25 mm 8.1 1.3 from 0.5 to 1.0 mm 33.3 68.2 from 0.25 to 0.5 mm 3.7 24.6 from 0.16 to 0.25 mm 0.3 2.6 <0.16 mm 0.7 2.6
[0027] The wheat bran should be moistened and heat-treated in order to pasteurize it or to sterilize it. It is advantageous that the heat treatment does not precede the moistening because poor fermentation results have been obtained if the bran is heat-treated before moistening. The heat treatment may consist in heating, for example, in an autoclave. An autoclave treatment of 20 min at 120˜121° C. has proved highly satisfactory, but less severe conditions (pasteurization at 105° C. for 15 min in an oven) are also suitable. It is also possible to carry out the heat treatment of the bran by injecting steam into it, which may make it possible to moisten the bran simultaneously.
[0028] The pH may advantageously be adjusted during moistening in the range from 4 to 5.5 in order to improve the pasteurizing effect of the heat treatment and the initiation of the desired fermentation.
[0029] In addition to its sterilizing function, the effect of the heat treatment is to promote gelatinization of the starch contained in the wheat bran and therefore the availability of this substrate for the fungus Aspergillus niger, which allows more effective fermentation.
[0030] The moistening of the bran is important because the water content influences the performance of the fermentation. The initial water content of the bran is initially adjusted to 50-60%, preferably 50-55%, of the total mass of the bran and of the water and it is substantially maintained in this range during fermentation, for example by periodically supplying water in order to compensate for the loss of water from the medium. The expression “substantially maintained” means that it is acceptable for the moisture level to take a value which varies slightly (±5% units) from the range 50-60% during a relatively brief period between two successive adjustments of the moisture level or at the end of fermentation. It is advantageous, in any case, not to drop below a moisture level of 45%. The moisture level of the culture medium tends to decrease during the culture through evaporation due to the increase in temperature generated by the fungal growth, said medium being a poor heat conductor. The quality of the water used also plays a significant role. Good quality running water or distilled water may be used.
[0031] The inoculation of the wheat bran may be performed with any appropriate inoculum. Persons skilled in the art know many ways of preparing a suitable inoculum from a selected strain. The inoculum dose is advantageously at least 1×10 7 spores/gram of initial dry matter.
[0032] The fermentation may be carried out in any appropriate reactor. Examples of a reactor which can be used are those described in the paper by A. DURAND et al., published in Agro-Food-Industry Hi-Tech (May-June 1997, pages 39-42).
[0033] The fermentation may be carried out for a period of 1 to 3 days, preferably of 30 to 60 hours. At less than 1 day, the fermentation is too incomplete. After 3 days, the fermentation is complete or practically complete and it would be uneconomical to prolong it further. The temperature of the medium is typically maintained between 28 and 38° C., preferably between 32 and 36° C., which corresponds to the optimum activity range known for the Aspergillus niger strains to be used in the invention. For this purpose, the air temperature is advantageously set at 34-38° C. for the first few hours of fermentation in order to promote germination of the spores, and then reduced to 28-32° C. for the remainder of the fermentation in order to contribute to the regulation of the temperature of the medium.
[0034] The pH of the fermentation medium is not usually regulated. If its starting value is close to 6.0-6.4, the pH decreases to 3.8-4.2 during culture but increases at the end. This change is generally correlated with the fungus sporulation phase. The variation of the pH constitutes a good indicator of the state of the culture.
[0035] The fermentor should be aerated, preferably continuously, in order to supply the oxygen necessary for fermentation and to avoid the excessive accumulation of carbon dioxide produced by fermentation. In addition, the aeration helps to control the temperature and the moisture of the culture medium. The air is preferably substantially saturated with water in order to limit the tendency for the medium to dry out. It is difficult to give quantitative information on the aeration rate because many variables, in particular the size and the geometry of the reactor, the quantity of its load, and the like, come into play. Simple routine trials will allow persons skilled in the art to easily determine a suitable aeration rate in each practical case, however.
[0036] The bran load in the fermentor should be periodically added during fermentation using stirring means, such as stirring arms, blades or spatulas, or lead screws so as to avoid the formation of impermeable masses and so that the aeration reaches the entire mass of bran as homogeneously as possible. Excessively vigorous stirring which could harm the fungus should be avoided, however.
[0037] The product of the invention is a solid product which is useful in particular for the production of ethanol from wheat. It may be directly added to liquefied starch (dextrins) obtained in the liquefaction stage, in order to carry out the saccharification. For this application, it is the glucoamylase activity which is the most important factor. A product of the invention will therefore preferably be used which has a glucoamylase activity of at least 750 GU, for example, preferably of at least 1 500 GU per gram of dry matter.
[0038] Another possible use of the product of the invention relates to the production of wheat-based feed for monogastric animals, for example poultry and pigs. In this application, it is the xylanase activity which constitutes the most important factor. A product will therefore be used in this application which preferably has a high xylanase activity, for example of at least 400 XU per gram of dry matter.
[0039] The product of the invention may be dried or frozen for storage, if desired.
[0040] The drying should be carried out at a moderate temperature so as not to affect the enzyme activity. Heating in an oven at 40° C. has proved to be appropriate, for example. Freezing may be carried out on the moist product at low temperature, for example at −20° C.
[0041] In the examples, the various enzyme activities were measured by the following methods:
[0042] a) Glucoamylase activity
[0043] The action of a glucoamylase (GA) preparation on a starch solution brings about the release of reducing sugars. Heated at 100° C. in the presence of 3,5-dinitrosalicylic acid (DNS), these compositions take on a brown color which is measured on a spectrophotometer (Kontron Instruments, Milan, Italy) at 540 nm.
[0044] The reaction medium contains
starch solution 1% 500 μl citrate buffer 0.1 at pH 4.5 450 μl enzyme solution: 50 μl
[0045] The reaction occurs for 30 min at 60° C. (55° C. for the A. orizae GAs). Samples are collected every 5 min, mixed with DNS and placed in an ice bath. They are then heated for 5 min at 100° C., rapidly cooled and then assayed at 540 nm.
[0046] These assay conditions were established after studying the influence of the temperature and the pH on the activity of the GA preparations. Merck soluble starch (Darmstadt, Germany) was used as substrate for this enzymatic hydrolysis. The DNS is prepared according to the following protocol proposed by P. Bernfeld, Methods in enzymology, 1, 149-159 (1955):
[0047] Dissolve beforehand:
[0048] 10 g of 3,5-dinitrosalicylic acid
[0049] 200 ml of 2 molar sodium hydroxide
[0050] 200 ml of distilled water.
[0051] Then add:
[0052] 300 g of sodium potassium tartrate.
[0053] Adjust the volume to 1 liter with distilled water after complete dissolution.
[0054] Once prepared, this reagent should be stored protected from light. The calibration curves were prepared with glucose as reference product for assaying the glucoamylase activity and for monitoring the liquefaction-saccharification reactions, and with xylose for measuring the xylanase activity.
[0055] One glucoamylase activity unit (GU) corresponds to the quantity of enzyme necessary to release one micromole of reducing ends per minute under the assay conditions with glucose as reference. The glucoamylase activity, calculated using the formula indicated below, is expressed relative to the quantity of initial dry matter (IDM):
A= ( P/Venz )*( Vferm/Mferm )
[0056] A is the GA activity expressed in GU.gIDM −1 (μmol.min −1 .gIDM −1 ),
[0057] P is the glucose equivalent release rate in μmol.min −1 ,
[0058] Venz is the volume of the enzyme solution assayed in ml,
[0059] Vferm is the total volume of distilled water used to extract the enzyme solution in ml,
[0060] Mferm, expressed in g of IDM, is the initial mass of dry product from which the enzyme solution was extracted.
[0061] b) Protease activity
[0062] This assay was developed on azocasein using the Béinon method described in “Protein Purification Methods—a Practical Approach”, Harris E. L. V. and Angal, S (Editors), IRL-Press, Oxford University Press, 1-66 (1989). The degradation of this substrate by proteases causes the release of azo groups which absorb UV at 340 nm. The variation of the absorbence during the kinetics of hydrolysis of this protein indicates the extent of the reaction.
[0063] The reaction medium contains:
Azocasein solution at 1%, pH 5.0 1000 μl Enzyme solution: 200 μl
[0064] The azocasein (Sigma, Saint-Louis, United States) is dissolved in a 0.1 M acetate buffer at pH 5.0. The protease activities were assayed at this pH because azocasein is insoluble in this acetate buffer at lower pH values. The enzyme reaction is carried out at 60° C. Samples are collected every 5 min for 20 min and mixed with 5% trichloroacetic acid (TCA) to stop the reaction.
[0065] One protease activity unit (PU) corresponds to the quantity of enzymes necessary for an increase of 0.01 A 340 nm unit per minute, generated by the release of azo groups under the conditions mentioned above. This activity, calculated based on the formula indicated below, is expressed relative to the initial dry matter (PU.G −1 IDM) or the glucoamylase activity (PU.GU −1 ):
A= ( P/Venz )*( Vferm/Mferm )
[0066] A is the protease activity expressed in PU.gIDM −1 ,
[0067] P is the rate of release of the azo groups expressed as an increase of 0.01 unit A 340 nm .min −1 ,
[0068] Venz is the volume of the enzyme solution assayed in ml,
[0069] Vferm is the total volume of distilled water used to extract the enzyme solution in ml,
[0070] Mferm, expressed in g of IDM, is the initial mass of dry product from which the enzyme solution was extracted.
[0071] c) Xylanase activity
[0072] To demonstrate this enzyme activity, the GA preparations are reacted with a soluble xylan solution and the reducing sugars released were measured by the DNS method.
[0073] The reaction medium is composed of:
Xylan solution at 1%, pH 4.5: 900 μl Enzyme solution: 100 μl
[0074] The solution of larch xylan (Sigma at 1%) is prepared in citrate buffer at pH 4.5 and the reaction occurs at 60° C. Samples are collected every 5 min for 20 min, mixed with DNS and placed in an ice bath. They are then assayed according to a protocol identical to that presented for the measurement of the GA activities with xylose as reference.
[0075] One xylanase activity unit (XU) corresponds to the quantity of enzymes necessary for the release of one micromole of reducing sugars per minute. This activity is expresssed relative to the initial dry matter (XU.g −1 IDM) or to the glucoamylase activity (XU.GU −1 ). To calculate this activity, the formula defined for the calculation of the GA activities is used again, in which:
[0076] A is the xylanase activity expressed in XU.gIDM −1 (μmol.min −1 .gIDM −1 ),
[0077] P is the rate of release of xylose equivalents in μmol.min −1 ,
[0078] the other terms of the formula are not modified.
[0079] The following nonlimiting examples are given to illustrate the invention.
EXAMPLE 1
Selection of Aspergillus Strains
[0080] The ability of seven different commercially available Aspergillus strains to produce glucoamylase by solid-state fermentation of wheat bran was studied in a comparative manner.
[0081] The trials were carried out on 50 g of fermentation medium in an Erlenmeyer flask. The medium consisted of 21.5 g of wheat bran, 27.5 g of water and 1 g of wheat starch. The initial pH of the medium was 6.0-6.5. The medium was sterilized for 20 min in an autoclave at 120° C.
[0082] Each medium was inoculated with 2×10 7 spores of the test strain per gram of initial dry matter. The age of the spores was 3 days. The fermentation was allowed to proceed for 40 to 50 hours, and the Erlenmeyer flasks were placed in an oven at 35° C. At the end of fermentation, the fermented medium was mixed with 150 ml of distilled water in order to take the enzymes produced into solution, and the mixture was then filtered to recover the enzyme solution. The solution was centrifuged to remove the residual particles and spores, and the solution was packaged in 100 ml vials which were stored at −20° C. until the glucoamylase activity was analyzed.
[0083] The strains tested and the results obtained are summarized in the following table 1:
Ref. strains from Duration of the SSF GA Ac. collections (h) (GU.g −1 IDM) A. niger ATCC 76060 50 627 A. niger ATCC 76061 50 943 A. niger MUCL 28815 40 710 A. niger MUCL 28816 40 631 A. niger NRRL 3112 50 1056 A. oryzae ATCC 22788 50 903 A. oryzae ATCC 42149 50 861
[0084] Note that the A. niger NRRL 3112, A. niger ATCC 76061 and A. oryzae ATCC 226788 strains have the best activities in terms of glucoamylase production.
[0085] However, another important property to be taken into consideration is the stability of the glucoamylase produced. Tests of heat-stability were therefore carried out by heat treating enzyme solutions at 55 and 60° C. for 30 min and measuring the glucoamylase activity at the end of this time. These treatments are similar to the conditions of use for the saccharification of starch. It was found that the A. niger ATCC 76061 and A. niger NRRL 3112 strains gave the most stable glucoamylases (100% residual activity after 30 min at 55° C. and about 50% residual activity after 30 min at 60° C.), whereas the A. Oryzae ATCC 22788 and ATCC 42149 strains gave glucoamylases having 0% residual activity after 30 min at 60° C. and 46% residual activity after 30 min at 55° C. The A. niger ATCC 76061 and NRRL 3112 strains were therefore selected. Moreover, the A. niger NRRL 3112 strain proved to be fairly unstable genetically (loss of activity after a few reproductive cycles) and so the most preferred strain is the A. niger ATCC 76061 strain. This strain was therefore used in the subsequent examples.
EXAMPLE 2
[0086] Production of glycoamylases in nonsterile 50 l pilot tanks provided by INRA: importance of the pretreatment of wheat bran.
[0087] The trials were carried out with a 50 l nonsterile fermentor like that described in the paper by A. DURAND et al., cited above, (FIG. 1 +L) and BCE wheat bran (provided by the distillery Brie Champagne Ethanol, Provins, France). Two methods of preparing the bran were used to obtain 5 kg culture medium containing 55% moisture:
[0088] dry bran: the bran is autoclaved for 1 h at 105° C. and then mixed with water (trial F4C3);
[0089] moist bran: the bran is moistened to 45% in a kneader and autoclaved for 20 min at 121° C. (trial F4C4).
[0090] In both cases, inoculation is carried out with 2×10 7 spores.g −1 DM and the water content of the media is adjusted to about 55%. They are then fermented over a 10 cm bed in aerated tanks. During these cultures, the medium is intermittently streaked using a spatula to reduce its temperature. During the fermentation, the atmosphere is continuously replaced with conditioned air whose temperature, moisture and flow rate are as indicated in the tables.
[0091] The results are presented in tables 2 (trial F4C3) and 3 (trial F4C4).
[0092] The data makes it possible to draw several conclusions:
[0093] Moistening the wheat bran prior to the heat treatment is necessary for an effective production of glucoamylases. Apart from decontamination, heat treatment of the wheat bran probably promotes gelatinization of starch;
[0094] The pH appears to be a good qualitative indicator of the variation of growth and of the production of fungal GA, but without making it possible to estimate the quantity of GA obtained:
[0095] Moderate stirring of the medium (streaking) does not adversely affect the production of enzymes;
[0096] The variation in the water content during these two fermentations indicates considerable drying of the culture medium, which could be damaging to fungal growth.
EXAMPLE 3
[0097] Production of glucoamylases in a pilot fermentor provided by the company FUJIWARA: importance of maintaining the moisture content of the medium during fermentation.
[0098] This trial was carried out with a pilot fermentor sold by the company FUJIWARA, Okayama, Japan, and BCE wheat bran. It differs in particular from the fermentor used in example 2 in the diameter of the tank, which is 0.66 m against 0.35 m for the INRA tanks. In this fermentor, 20 kg of medium containing 55% water prepared according the moist bran method described in example 2 are necessary to carry out a culture on a thickness of 12 cm. The stirring is provided by three continuously rotating vertical lead screws mixing the medium in the tank under rotation (5-10 min/revolution). During the fermentation, as with the INRA tanks in example 2, the gaseous atmosphere is continuously replaced with conditioned air whose temperature, moisture and flow rate are as indicated in table 4.
[0099] During this trial, called FII, the opportunity for regulating moisture content was studied. Localized measurements of the moisture content of the culture, carried out with an infrared apparatus, and of the mass of the medium are used to determine the quantity of water to be added in order to maintain the water content of the medium above 50%.
[0100] The results of this FII trial are presented in table 4. The results obtained merit the following comments:
[0101] the FII trial clearly indicates that maintaining the water content between 50 and 55% promotes the production of enzymes with 1600 GU/g DM released after 44 h of fermentation, that is more than double the activity obtained during the F4C2 trial of example 2, which did not have this regulation;
[0102] stabilizing the production of enzymes from 44 h of culture correlated with the appearance of fungal spores, shows that it is not necessary to continue the culture beyond this phase;
[0103] satisfactory regulation of the temperature of the medium at around 35° C. may be obtained by a good combination of conditioning of the air and stirring of the medium;
[0104] the culture withstands, with no damage, intermittent mixing performed by the stirring system of the FUJIWARA fermentor.
EXAMPLE 4
[0105] Production of glucoamylases in a 50 l stirred INRA pilot fermentor: usefulness of heat pretreatment of the bran with steam and culture under “sterile conditions”.
[0106] This pilot fermentor is similar to that presented in WO-A-94 18306 and in FIG. 4 of the article by A. DURAND et al. cited above. This tool makes it possible to treat the bran with steam directly in the fermentor, a method of preparation which is preferred at the industrial level. The culture is also prepared, inoculated and carried out under sterile conditions, with the exception of the sample collections, which confers semisterility on this trial and differs from the preceding two examples.
[0107] A) Experimental conditions
[0108] 9 kg of BCE bran premoistened with 1.5 l of water are introduced into the fermentor and then sterilized in situ for 20 minutes at 121° C., with periodic stirring for 5 seconds every 5 minutes. This treatment makes it possible to reach a moisture level of 46% which is then adjusted to 55% during inoculation.
[0109] The bran is inoculated with a koji-type preparation:
[0110] 180 g of BCE bran (55% initial moisture) fermented for 4 days at 35° C. are mixed with 3 liters of sterilized water to obtain a suspension of spores which constitutes the inoculum.
[0111] The initial fermentation conditions are as follows:
[0112] 18.3 kg of culture with 55% moisture and an initial pH of 5.7;
[0113] bed height 40 cm;
[0114] aeration rate: 314 l.min −1 ;
[0115] temperature of inlet air: 35° C.;
[0116] relative humidity of inlet air: 95%.
[0117] B) Monitoring Fermentation
[0118] In addition to measuring the pH, the temperature of the medium, the percentage of dry matter and the production of GA, the variation in the mass of the culture is continuously recorded on the 50 l stirred fermentor; for the nonsterile reactor, the culture is weighed after 21 h and 42 h of fermentation.
[0119] The importance of these measurements of the mass are two-fold:
[0120] Maintaining the Moisture During Culture by Estimating the Percentage DM
[0121] During fermentation, two phenomena contribute to reducing the mass of the culture; they are:
[0122] drying of the medium, which is compensated by supplying water,
[0123] loss of dry matter, which is linked to the growth of the fungus.
[0124] This loss of dry matter is not negligible, 20% DM being lost in 40 h of culture, that is 0.5% DM per hour if linear losses are assumed for the purposes of approximation.
[0125] From that, knowing the instantaneous mass of culture (M (t) ), it is possible to deduce therefrom the theoretical percentage of DM at time t, from the formula:
% DM theoretical ( t ) = IDM ( IDM .0 .5 ) · t M ( t )
[0126] where IDM is the quantity of initial dry matter.
[0127] When the % DM calculated in this way exceeds 50%, sterilized water is added to reduce this percentage to 45%.
[0128] Expressions of the Results Per Gram of Initial DM
[0129] The variations in the mass and the percentage of DM measured make it possible to calculate the loss of real dry matter (L DM expressed in %) during culture. Thus, the quantity of GA expressed thus far in GU.g −1 DM may be expressed as GU.g −1 initial DM using the following formula:
( GU.g −1 IDM )= GU.g −1 DM ).(100− L DM )/100
[0130] C) Results
[0131] Tables 5 and 6 summarize the operating conditions and the results obtained on steam bran in a stirred reactor.
[0132] Despite aerating the culture with moisture-saturated air, the drying of the medium is such that it was necessary to readjust its water content when it decreased below 50% on two occasions, as indicated in table 5.
[0133] It was possible to maintain the temperature of the medium at an average value of 35° C. by decreasing the inlet air, but in particular by intermittent stirring.
[0134] Under these culture conditions, the growth of the fungus, whose progress was monitored by measuring the pH, is maintained for 60 h and makes it possible to reach a production of 1436 GU.g −1 DM in 44 h and 1990 GU.g −1 DM in 63 h. Expressed relative to the initial DM, the quantity of GA produced is 1160 and 1540 GU.g −1 IDM, respectively. For comparison, in the context of example 3, in 44 h of culture, 1605 GU.g −1 DM, equivalent to 1067 GU.g −1 IDM was obtained. This is advantageous because it indicates that the productivity of these two trials is identical, but that the experimental conditions of example 4 made it possible to prolong the production of enzymes even with a 40 cm bed.
[0135] The treatment of the bran with steam followed by fermentation in the 50 l stirred INRA reactor therefore prolongs the fungal culture and the production of enzymes.
[0136] Expressed relative to the initial DM, the quantity of GA produced is 1540 GU.g −1 IDM.
[0137] Assays of xylanase and protease activities were carried out on the same samples. The results obtained are very satisfactory with a maximum, on average, at 50 h of fermentation of
[0138] 350 XU.g −1 IDM for the xylanases;
[0139] 400 PU.g −1 IDM for the proteases.
[0140] By virtue of the continuous recording of the mass, it was possible to calculate the loss of dry matter during the culture. It is about 23% after 60 h of culture (to within 2% given the accuracy of weighing).
EXAMPLE 5
Use of the Fermented Brans Produced in Example 4 for the Hydrolysis of Wheat Flours
[0141] A series of saccharifications with the fermented brans obtained in example 4 was carried out on wheat flours previously subjected to conventional enzymatic liquefaction treatment. The glucoamylase preparation AMG 300L® sold by the company NOVO served as a control. These trials were carried out with a 45-type conventional wheat flour. The operating conditions are summarized in table 7 for 750 g of wort.
TABLE 7 AMG Dried fermented Product 300L ® (Novo) Fermented bran bran Reference ANG 300 L Ex. 4 Ex. 4 Presentation Liquid Wet bran Dry bran Preservation at +5° C. at −20° C. at room T method Flour Commercial Commercial Commercial type 45 type 45 type 45 Quantity 300 300 300 used (g) Dry matter 35 35 35 of the medium (%) Liquefaction 1 h/88° C./pH 6.1 1 h/88° C./pH 6.2 1 h/88° C./pH 6.2 cond. Enzyme 125 μl Termamyl. 125 μl Termamyl. 125 μl Termamyl. 120L ® 120L ® 120L ® Saccharif. 44 h/58° C./ 40 h/58° C./ 44 h/60° C./ Cond. pH 4.6 pH 4.55 pH 4.52 Qt. Equiv. 205 μl 4.3 g 2.1 g to 3500 GU
[0142] During these hydrolyses of wheat flour, three samples of medium were collected each time. The results of concentrations of reducing sugars (RS) at various times of the saccharification presented in table 8 are the average of these three samples. These assays, carried out by the DNS technique, were carried out on the supernatants of the centrifuged samples. The final viscosity of the saccharified products was also measured.
TABLE 8 AMG 300L ® Fermented Dried Measurements (Novo) bran fermented bran RS conc. 180.9 ± 4.6 185.0 ± 3.1 171.5 ± 4.5 (initial (g/l)) Final RS conc. 327.5 ± 18.5 325.0 ± 22.5 348.3 ± 19.1 (g/l) Viscosity 6.80 2.82 2.80 (mPa.s)
[0143] Moreover, an increase was observed in the soluble nitrogen content of the worts after saccharification due to the proteolytic action of the fermented bran.
[0144] These results indicate that the fermented brans produced in example 4 are capable of hydrolyzing wheat flour with the same efficacy as a standard GA preparation, regardless of their method of storage.
[0145] The hydrolysis of the flour with fermented bran also results in a notable reduction in viscosity compared with a conventional enzymatic preparation.
EXAMPLE 6
[0146] This example illustrates the possibility of producing a considerable quantity of xylanases and a small quantity of glucoamylases with the Aspergillus niger strain.
[0147] This trial was carried out in a Fujiwara pilot fermentor with BCE bran and an A. niger Ref. ATCC 210202 strain known for its capacity to produce xylanases. The operation of the pilot fermentor is described in example 3. 20 kg of medium containing 55% moisture, prepared as in example 2, are used in this example. As in example 3, during the fermentation, the moisture of the medium was maintained above 50% and the temperature of the medium regulated at around 35° C.
[0148] After 37 hours under these fermentation conditions, the A. niger ATCC 201202 strain produced a fermented bran having 727 XU/g DM and 162 GU/g DM.
EXAMPLE 7
[0149] Advantage of incorporating fermented bran according to the invention into a wheat-based poultry feed intended for broilers.
[0150] The hemicellulases in wheat flours are known to be partially soluble in water and to increase the viscosity of the intestinal content, thus reducing the release and absorption of nutrients.
[0151] It has been demonstrated that the addition of hemicellulases causes degradation of hemicelluloses, thus making it possible to reduce the viscosity of the intestinal content and to improve the zootechnical performance of monogastric animals such as broilers fed with feed in which the only cereal is wheat.
[0152] An experiment was carried out on 1200 Ross broilers to show the advantage of using fermented bran carrying hemicellulase (xylanase) activity, compared with feed without enzyme and feed containing a standard source of xylanase, the product Avizyme. Feeds with or without enzyme were prepared so as to feed 4 groups of 300 chicks. Their composition is detailed in table 9. The growth feeds (GR FE) were used for the first 21 days of breeding and were then replaced with finishing feed (FI FE) for 18 days.
TABLE 9 Feed GR FE FI FE Moisture (%) 10.6 11.4 Proteins (%) 21.3 19.1 Fatty substances (%) 6.1 6.4
[0153] Feed 1 received no enzyme. Feeds 2 and 3 were supplemented with 3 and 5 kg, respectively, of fermented bran per ton of feed. Feed 4 was supplemented with 0.6 kg of Avizyme® per ton of feed.
[0154] The results of this test after 39 days of breeding are summarized in table 10.
TABLE 10 Feed 1 2 3 4 Fermented bran according to the — 3.0 5.0 — invention (kg/ton) a AVIZYME Finfeed (kg/ton) b — — — 0.6 Xylanase activity (XU/kg feed) — 1 700 2 840 1 620 Feed conversion ratio 39 days c 1.775 1.748 1.738 1.745 Reduction feed conv. ratio — 1.52 2.08 1.69 (% feed 1) d Mortality (%) 2.3 2.0 3.0 2.3
[0155] a. this fermented bran exhibited a glucoamylase activity of 1000 GU/g of dry matter, a proteolytic activity of 125 PU/g of dry matter and a xylanase activity of 600 XU/g of dry matter;
[0156] b. Avizyme® is provided by the company Finfeed, Finland;
[0157] c. ratio of weight of feed consumed/weight gain;
[0158] d. this is the reduction, in %, of the weight of feed consumed relative to the weight of feed 1 (without enzyme) consumed.
[0159] The incorporation of fermented bran into a poultry feed (3 or 5 kg/ton) made it possible significantly to reduce the feed conversion ratio. Under the trial conditions, the use of a dose of fermented bran greater than 3 kg/ton appears to be of no practical benefit. The improvements observed are comparable to those obtained with the commercial product Avizyme (0.6 kg/ton). The use of the fermented bran nevertheless has the advantage of being less expensive than the use of the commercial enzymatic product.
[0160] It goes without saying that the embodiments described are only examples and they can be modified, in particular by substitution of technical equivalents, without thereby departing from the scope of the invention.
TABLE 5 Physicochemical parameters of the SSF in a 50 1 stirred fermentor on its steam Cult. Time Air, inlet T Air, flow rate Average T Average Total (t) (° C.) (1/min) Air, % RH medium pH mass Treatment 0 35.0 314.0 94.6 5.70 18.30 13 36.1 312.7 92.6 38.8 4.72 18.00 13 (after 471.0 38.6 4.68 stirring stirring) 16 29.8 448.6 94.6 32.4 4.60 17.50 stirring 18 33.2 466.5 77.2 31.0 4.37 17.10 20.33 32.6 466.5 93.7 34.3 4.20 16.80 23.66 34.2 4.13 15.80 26 29.8 467.5 94.6 32.9 4.17 15.10 26 29.8 467.5 94.6 33.3 3.81 17.30 stirring + 2.5 1 of water 36.75 29.0 467.5 94.6 stirring 36.75 27.0 467.5 94.6 29.9 3.71 14.30 40.58 27.0 467.5 94.6 31.0 4.20 13.10 40.66 27.0 467.5 94.6 31.7 3.60 15.10 stirring + 2.1 1 of water 44.58 448.6 33.6 3.71 14.10 47.17 467.5 34.8 4.04 13.30 50 27.0 303.3 94.6 32.0 4.09 12.80 stirring 63.33 28.7 303.0 31.0 5.75 10.30
[0161] [0161] TABLE 6 Summary of the results of the SSF on bran treated with steam in a 50 1 stirred fermentor Cult. Water Time content Loss of DM Loss of DM Average Average (h) (%) (%) % (smoothed) GU/g DM GU/g IDM XU/g DM XU/g IDM PU/g DM PU/g IDM 0 54.50 −2.07 0.00 0.00 0.0 0.0 0.0 0.0 13 57.52 7.78 0.4 92.69 85.48 16.1 16.0 131.0 130.49 16 53.72 2.11 1.0 170.53 166.92 19.2 19.0 196.2 194.15 18 55.23 7.21 1.8 129.25 222.02 27.9 27.4 103.9 102.02 20.33 51.90 1.91 3.1 429.36 421.18 35.0 33.9 193.7 187.63 23.66 50.88 5.57 5.9 551.93 521.21 51.0 48.0 283.4 266.81 26 49.06 6.15 8.2 651.45 611.36 75.4 69.2 296.5 272.14 26 57.76 10.57 8.2 548.42 490.44 54.1 49.7 262.1 240.57 36.75 49.27 10.75 18.4 1127.09 1005.88 203.5 166.2 359.1 293.20 40.58 51.14 20.55 20.5 40.66 58.72 22.54 22.0 1278.58 990.35 227.3 180.7 347.9 276.52 44.58 54.10 19.21 22.6 1436.16 1160.27 408.3 318.6 367.1 286.45 47.17 54.01 23.07 23.2 1535.69 1181.43 511.5 395.7 496.8 384.30 50 54.66 26.67 24.4 1742.78 1277.91 429.8 330.1 628.2 482.48 63.33 44.69 22.62 22.6 1989.07 1539.07 410.3 310.1 478.3 361.5
[0162] [0162] TABLE 2 Cult. Air, Air, flow Air flow Cult. Time inlet T rate rate Air, Average T Average % Average Time (h) (° C.) (1/min) (m/s) % RH medium pH moisture GUA/g DM (h) F4C3 0.0 35 174.4 8.0 96 25.0 0.0 dry bran 3.0 35 174.4 8.0 95 33.8 6.33 3.0 11.0 32 174.4 8.0 94 34.6 5.13 54.53 20.56 11.0 14.0 30 174.4 8.0 95 35.4 4.38 54.19 71.13 14.0 streaking 16.0 30 174.4 8.0 94 33.3 4.36 52.17 123.12 16.0 (17 h) streaking 18.0 28 174.4 8.0 92 37.4 4.51 51.31 85.78 18.0 (18 h) 20.0 28 174.4 8.0 96 31.8 3.79 49.54 132.81 20.0 22.0 28 174.4 8.0 95 34.7 4.12 45.17 188.0 22.0 25.0 28 174.4 8.0 37.6 4.34 45.13 181.03 25.0 28.0 28 174.4 8.0 94 32.6 4.63 36.47 129.58 28.0 31.0 28 174.4 8.0 32.8 5.05 30.68 198.10 31.0 40.0 28 174.4 8.0 95 31.9 5.69 23.96 246.86 40.0
[0163] [0163] TABLE 3 Cult. Air, Air, flow Air flow Cult. Time inlet T rate rate Air, % Average T Average % Average Time (h) (° C.) (1/min) (m/s) RH medium pH moisture GUA/g DM (h) F4C4 0.0 35 174.4 8.0 96 25.0 5.96 0.0 dry bran 3.0 35 174.4 8.0 95 33.8 6.12 3.0 11.0 32 174.4 8.0 94 35.1 5.06 53.93 135.77 11.0 streaking 14.0 30 174.4 8.0 95 39.9 4.66 53.04 121.02 14.0 (14 h) 16.0 30 174.4 8.0 94 33.1 4.59 51.53 182.96 16.0 streaking 18.0 28 174.4 8.0 92 38.0 4.48 50.80 327.41 18.0 (18 h) 20.0 28 174.4 8.0 96 34.3 3.72 51.76 360.25 20.0 22.0 28 174.4 8.0 95 36.9 3.70 47.65 618.00 22.0 25.0 28 174.4 8.0 36.3 4.15 41.68 658.05 25.0 28.0 28 174.4 8.0 94 30.9 4.53 35.73 660.03 28.0 31.0 28 174.4 8.0 30.8 5.18 33.98 583.62 31.0 40.0 28 174.4 8.0 95 30.2 4.88 30.02 702.74 40.0
[0164] [0164] TABLE 4 Rate of T ° C. Time ventilation Moisture air T ° C. Moisture Time (h) rev./min air (%) inlet medium medium % pH GU/g DM GU/g IDM (h) stirring 0 15 99.0 35.0 25.0 54.0 6.36 4.3 4.3 0 10 15 98.5 35.0 34.7 53.7 5.95 23.9 10 12 33.0 12 15 15 98.6 33.0 34.5 51.6 4.92 133.3 15 stirred + 3 1 18 15 98.8 33.0 37.3 49.7 4.18 304.8 273.1 18 of water 21 15 98.3 30.0 30.7 54.7 3.83 472.1 21 24 15 98.2 30.0 31.9 52.4 3.76 709.2 24 stirred + 2 1 28 15 97.9 30.0 33.4 46.6 4.08 1198.0 28 of water 29 25 98.0 30.0 51.6 1054.0 29 stirred + 6 1 38 15 98.6 32.0 31.5 39.2 5.00 1469.7 976.1 38 of water 39 15 99.0 32.0 60.6 1338.0 39 42 15 99.2 32.0 33.9 59.7 5.28 1514.8 42 44 15 98.1 32.0 34.1 54.8 5.76 1605.1 1067.6 44 46 15 96.8 32.0 33.7 52.6 6.33 1601.0 46 66 15 99.0 32.0 32.4 34.0 7.28 1594.4 1161.7 66 | The invention concerns a multi-enzyme product with glucoamylase, proteolytic and xylanase activities, characterized in that it consists of wheat bran fermented with an Aspergillus niger strain, said enzymatic glucoamylase, proteolytic and xylanase activities being present in the following minimum values: glucoamylase activity: at least 100 UG per gram of dry matter; proteolytic activity: at least 100 UP per gram of dry matter; xylanase activity: at least 100 UX per gram of dry matter, provided that at least one of the following conditions is satisfied:
the gluycoamylase activity is at least 750 UG per gram of dry matter
the xylanase is at least 300 UX per gram of dry matter. The invention is useful for producing ethanol or monogastric animal feed. | 2 |
FIELD OF THE INVENTION
[0001] The present invention is in the field of fishing (Class 43), and relates to holders (subclass 54.1) comprising a receptacle specifically designed for use in fishing for holding the bait. Specifically, the present invention relates to live bait holders (subclass 55) designed to keep such bait in a fresh condition. More specifically, the invention relates to live bait holders including some means for freshening the water, and for protecting the live bait against special harm when the holder is placed in water (subclass 56).
SUMMARY OF THE INVENTION
[0002] The present invention is a dynamic flow live bait holder for in water use. The bail holder is “dynamic flow” in that it is adapted to utilize motion of the holder while in use to pump ambient water into the bait holder and internal water out, as a means for freshening the internal water. Additionally, the present live bait holder has an interior/receptacle space for holding the bait which has no internal corners. The corner-less interior space is a feature that provides for protecting the live bait against certain kinds of harm when the holder is placed in water.
[0003] The present dynamic flow live bait keeper comprises a keeper body, which is a hollow and buoyant disc-shaped housing for containing the bait. The body or housing is formed of two concave disc shaped members faced together. The disc shaped member form the top and bottom portions of the keeper body, and define the interior space. Substantially, the keeper body has no definable sides joined at an angle in the interior space. The largest cross-section of the interior space is substantially oblong and of sufficient dimensions to allow the bait fish to swim without bunching up (e.g., in corners). The corner-less feature of the interior space facilitates the object of the present invention of protecting the live bait against harm when the bait holder is placed in water by allowing the bait to be able to swim in a continuous course and to avoid bunching up against walls and corners in the receptacle space.
[0004] The present live bait holder has water & air vent-ports disposed on the keeper body. Top-ports are positioned on the top-portion of the keeper body to vent air and allow excess water to escape from the interior space, and bottom-ports are positioned on the bottom-portion of the keeper body primarily to allow water to enter the interior space of the keeper body. It is a feature of the present invention that there be bottom-ports, and that the bottom-ports are positioned toward the forward-end of the bottom-portion of the keeper body to allow water to enter the interior space. A hatch assembly is disposed on the top-portion of the keeper body and is operable to provide access to the interior space of the bait holder. A tether attachment is disposed on the forward end of the bottom-portion of the keeper body. When in use in the water (e.g., tethered to the angler or to a boat), the bait holder maintains its forward end into a wind and/or a current at a surface of the water.
[0005] Generally, the buoyancy of the present live bait holder is adjusted so that at neutral buoyancy, its draft when placed in water is proximate the plane of the keeper body's largest interior cross-section. Buoyancy can easily be adjusted by a user by the addition of weight to a desired place on/in the keeper body. It is also a feature of the present invention that the forward-end of the top portion of the keeper body curves downward. This feature serves to more forcefully drive the forward-end downward when the forward-end gets submerged in a current, to increase the pressure driving ambient water into the bottom-ports in the bottom-portion of the keeper body. Additionally, a porpoise weight can be disposed near the front end of the keeper body to promote movement of the forward-end of the keeper body with a rising and falling motion in response to the wind and current at the surface of the water. This motion helps to force water through the bottom-ports and into the interior space of the keeper body, to provide the dynamic flow of ambient water into the present live bait holder.
DESCRIPTION OF THE INVENTION
[0006] Referring now to the drawings, the details of preferred embodiments of the present invention are graphically and schematically illustrated. Like elements in the drawings are represented by like numbers, and any similar elements are represented by like numbers with a different lower case letter suffix. The present invention is an in the water, dynamic flow live bait holder. The “dynamic flow” feature of the bait keeper derives from the structural elements of the bait keeper and their interaction when the bait keeper is placed in water, as will be explained below.
[0007] The dynamic flow bait holder has a keeper body which is a hollow and buoyant, and substantially disc-shaped container. The keeper body has a forward end, and an aft end as well as a top-portion and a bottom-portion. In one embodiment, the bottom-portion of the forward end has a tether attachment means. Additionally, the top-portion of the keeper body has a closeable hatch assembly, which allows access to a “corner-less” interior space of the body. The interior space of the keeper body is “corner-less” in that a perimeter around the largest dimension of the interior space is curved (and substantially circular) and there are no corner (i.e., sharp angles) in the interior space. This is an important structural feature of the present invention which helps live bait to be able to avoid bunching up (at a corner) and to keep swimming. The keeper body also has a number of vent ports on its top-portion and bottom-portion, which allow water flow between the interior space and the environment outside of the keeper body.
[0008] The keeper body has a hatch opening through its top-portion, which opening enables a user to access the interior space of the bait keeper. The hatch assembly is disposed on the top-portion of the keeper body to allow the hatch opening to be closed to prevent bait from escaping from the interior space of the keeper body. The hatch assembly includes a hatch door, a hinging means attaching the hatch assembly to the keeper body, and a latch for securing the hatch door closed. The interior space of the keeper body is “corner-less” in that a perimeter around the largest dimension of the interior space is curved (and substantially circular) and there are no corner spaces (sharp angles) in the interior space. This is an important structural feature of the present invention which helps live bait to be able to avoid bunching up (at a corner) and to keep swimming, which helps to keep the bait fresh longer. It is this feature that defines the substantially circular and oval shape of the bait keeper.
[0009] In use, the present dynamic flow live bait keeper is placed in the water where a person (such as a fisherman) intends to use it. The bait keeper is buoyant and floats in the water. Once the bait holder is placed in the water, it will fill with water to its neutral buoyancy level. Live bait is placed into the interior space of the keeper body through the hatch door and the hatch door closed. Similarly, bait may be removed from the bait holder as desired by the user. One end of a tether line is attached to the tether attachment of the keeper body. The other end of the line is attached to the fisherman his/herself, to a fishing boat or water craft, or to something stationary in the water. The force of the wind, or current in the water, or the motion the bait keeper over the water takes the bait keeper to the end of the tether line. Selection of an appropriate composition and length of tether line is readily accomplishable by a fisherman of ordinary skill in the art. Once the forces on the bait keeper take it to the end of the tether line, the forward end of the keeper body points into the force(s) acting on it. Optionally, a skeg may be added to the bottom-portion of the keeper body to facilitate keeping the forward end pointed into the force acting on the keeper body.
[0010] Once the bait keeper is taken to the end of the tether line, the force continues to act on it. Even very small forces, such as ripples and swells in the water, or movement of the fisherman or water craft, will cause the keeper body to rock back and forth (i.e., to porpoise forward end to aft end) in the water. The keeper body of the bait holder may be disposed to float level in still water, but preferable it floats in still water with a slight forward end down tilt. In a preferred embodiment, the forward end is heavier than the aft end to accomplish a nose or forward end down tilt to the bait holder. The nose down tilt disposition of the forward end can be accomplished by having the front end of the keeper body have a thickness that is greater than the thickness anywhere else on the keeper body. Alternatively or additionally, a porpoise weight can be added to the front end. The porpoise weight is a denser-than-water putty or resin applied to the inside wall of the interior space, proximate the forward end. Molding the porpoise weight into the wall of the front end and/or using a dense putty as the porpoise weight both have the advantage of maintaining the “corner-less” element of the interior space of the keeper body. Other weighting means are known to and selectable by one of ordinary skill in the art for practice in the present invention that do not compromise the “corner-less” element of the keeper body. For example, a fin or skeg (not shown) could be added to the front end of the keeper body to add weight to the front end and to help stabilize the keeper body in line with the direction of the force on it.
[0011] The degree of nose (forward end) down tilt can be adjusted by a user by adding or removing a buoyancy means to the bait holder. For example, a buoyancy means in the form of a closed-cell foam strip fixed to the inside wall of the interior space. Other weighting and buoyancy adjustment means are known to and selectable by one of ordinary skill in the art for practice in the present invention.
[0012] The “dynamic” limitation of the present live bait holder refers to the water pumping action of the keeper body as it rises and fall (porpoises) in the water. The point of attachment of the other end (not shown) of the tether line is disposed so that when the bait holder tugs at the end of the tether line, the front end of the keeper body tends to rise up out of the water. This can be accomplished by attaching the other end of the tether line to a point that is out of the water. The benefit of the dynamic limitation of the bait holder derives from the fact that in open water a floating object is almost never still. And as noted above, even very small forces, such as ripples and swells in the water, or small movement of the fisherman or boat will cause the keeper body to rock back and forth or to porpoise in the water.
[0013] As the bait holder rocks back and forth in the water, the front end of the keeper body rises out of the water. Due to the weight of the keeper body front end and because the kinetic energy of the water contained within the interior space is greater than the water outside the keeper body, the bait holder is no longer neutrally buoyant in the water. This is not withstanding that some of the interior water flows out of the bait holder through the bottom-portion ports. The increase in the kinetic energy of the front end of the keeper body due to its mass and the water it contains causes the front end to forcibly reenter the water. As the front end enters the water (it tends to pass through the neutral buoyancy level of the keeper body), the bottom-portion ports submerge below the surface of the water. Water then enters the interior space of the keeper body, replacing an amount of the water that had flowed out of the interior space when the front end of the of the keeper body was out of the water. The top-portion vent ports vent displaced air and excess water from the interior space and minimize potential water pressure build-up in the interior space regardless of the water pressure outside of the bait holder. As the front end returns toward neutral buoyancy, excess water in the interior space flows out through the bottom-portion ports.
[0014] In the above manner, as the present dynamic flow live bait holder rocks or porpoises back and forth in the water, some portion of the water contained in its interior space is removed and replaced with fresh water. Consequently, the water in the interior space is constantly refreshed. Additionally, the water pressure in the interior space is relative constant and substantially independent of the water outside of the bait holder even when the force is relatively high, as when the bait holder is being towed behind a boat. The constant pressure feature of the present live bait holder is an advantage that helps keep live bait fresh.
[0015] While the above description contains many specifics, these should not be construed as limitations on the scope of the invention, but rather as exemplifications of one or another preferred embodiment thereof. Many other variations are possible, which would be obvious to one skilled in the art. Accordingly, the scope of the invention should be determined by the scope of the appended claims and their equivalents, and not just by the embodiments. | Disclosed is a live bait keeper having a cornerless interior and dynamic flow of ambient water through it for freshening the water and protecting bait against harm when the holder is in water. The holder has a hollow, disc-shaped keeper body having forward and aft ends and cornerless interior space. The keeper is buoyant. A top hatch accesses the interior where bait is held. In use, ports on the top-portion of the keeper vent air and water from the interior, and bottom-ports disposed toward the forward-end of the keeper allow water to enter the interior. A tether attachment is disposed on the bottom-portion at the forward end below the neutral buoyancy plane of the keeper body, and as a tether maintains the forward end into the wind and/or current, the keeper rocks fore and aft forcing water into the bottom-ports to provide dynamic water flow into the bait holder. | 0 |
This is a continuation-in-part of U.S. application Ser. No. 12/832,749 filed Jul. 8, 2010 now U.S. Pat. No. 8,157,091 which is a continuation-in-part of U.S. application Ser. No. 12/390,095 filed Feb. 20, 2009 now abandoned and claims the benefit thereof which claims benefit of U.S. Ser. No. 61/128,839 filed May 27, 2008.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to paint brushes and, more particularly, to a paint brush protective cover that protects the bristles of paint brushes from being damaged during wet or dry storage or nonuse thereby extending the life of the paint brush.
2. Related Art
In cases where a purchaser opts to purchase a paint brush to perform a painting job, there is a choice of brush shape, size and different filament materials. A professional painter can own many brushes, each with its own use. Typically each project can require several brushes, for large areas a 3 or 4 inch is used for general cutting in large pieces or general use whereas and for trim a 1½ inch works well. On a professional site there may be a crew of painters each using several brushes.
Fine paint brushes are expensive however they are required for a professional job as they apply a smoother finish with less brush strokes and paint faster and with less effort. If properly cleaned and stored they will last for years and conversely if not will have a short life. Inexpensive paint brushes can shed bristles into the finish and are difficult to work with, producing an inferior finish.
Paint brushes are categorized according to the type of coating being applied; water based paints and primers, such as latex or acrylic paints and primer plus water based epoxy; oil based paints and primers, such as alkyd paints and primers plus oil based epoxies; solvent thinned paints and primers; water based clear wood finishes and stains, such as acrylic urethane, water based polyurethane and its variants plus water based wood stains; oil based clear wood finishes and stains; this includes the common varnish and polyurethane plus oil based wood stains; all solvent thinned clear finishes and wood stains; shellac primers and clear finishes, such as tinted and clear shellac is thinned with denatured alcohol.
Each of these “types” of coatings or stains has a specific type of brush that is used. Type of paint brush refers to the filaments used in its construction. These filaments can be synthetic, natural, or a combination of the two. Synthetic refers to different types of plastics used to make the filaments, nylon and polyester or blends of the two. Natural refers to animal hair that is used in the brushes construction, this type of filaments are called bristles. Filaments are designed for specific solvents and will be damaged if used in the wrong solvent or improperly stored.
Synthetic brushes loose there shape in oil base paints and primers, an oil paint brush must be stiff enough to hold its shape and soft enough not to leave to many brush marks. Brush manufactures use a blend of different natural bristles to change the softness and stiffness for performing a job, for example, one having the stiffness for cutting in a straight line and thicker hair for holding more paint or one suited for varnishes, polyurethane and stains or one's for clear wood finishes require a very soft brush for the best results.
Bristle brushes cannot be used with latex paints or be cleaned with water this will ruin the brush. Natural bristle paint brushes absorb water and loose their shape, becoming impossible to control. However, cleaning the brush after every use is not desirable as it takes time and use of costly solvents.
It is desirable to leave the brush wet. Some painters leave the brush in a zip lock bag or in a bucket of paint. While this prevents cleanup, it often results in the disfigurement of the bristles. This is particularly problematic with cut-in brushes which come in a variety of shapes such as angular, flat, and oval, and size ranges from 1-6 inches wide and if disfigured become useless.
Fine paint brushes typically are expensive. User's of fine paint brushes, such as professionals, require excellent coverage from their paint brush, durability from their paint brush, greater efficiency in production, precise lines, proven results for smooth finishes and a lack of bristles or filaments left behind from the paint brush. When a paint brush no longer is capable of producing, the paint brush will be discarded and a new paint brush is purchased to replace the old paint brush.
After a job is finished, the brush must be cleaned in an appropriate solution to remove all of the remaining paint. Sometimes the bristles tend to separate and fray off in non-uniform directions and become a problem for the next usage so care must be taken to store the brush in a manner wherein the bristles can be maintained aligned.
Covers that the paint brushes are sold in are made of paper and are rather flimsy and easily tear and do not last very long. If no protective cover is used, in addition to the above described disfigurement occurring, dust and other particles generally stick and become imbedded inside the bristles. These particles will collect on the paint producing non-uniform streaks of paint during use.
Prior attempts to cover paint brushes include conventional paper or plastic covers which substantially fold about the bristles to maintain the filament shape. Some cases provide for air holes so that the filaments can dry after cleaning is performed.
The problem which is not addressed is that of wet media storage. Painters need a simple and easy cover for both dry and wet storage of the brushes which protects the filaments. There is also a need for quick, safe and easy transportation of brushes. Therefore, a need exists to provide an improved paint brush protective cover. The improved paint brush cover must be simple to use, allow for wet and dry storage, easy cleanup and durability and be inexpensive.
SUMMARY OF THE INVENTION
It is an object to improve paint brush covers.
It is a further object to provide a wet/dry paint brush cover.
It is another object to provide an improved paint brush protective cover that is simple to use.
Yet another object is to provide an improved paint brush protective cover that is durable.
It is another object to provide an improved paint brush protective cover that is inexpensive.
Still another object is to provide safe and easy transport of a paint brush.
A further object is to provide a user with a productivity guide for the brush.
Another object is to enable storage of a brush in wet media.
Accordingly, one embodiment of the invention is directed to a paint brush protective cover for a paint brush having filaments, a collar retaining the filaments and handle. The brush cover which includes a jacket having a hollow interior section, wherein the jacket has a first panel and a second panel removably connectable to the first panel in a manner to be maintained in a predetermined spaced relation to receive the paint brush therebetween, wherein each panel has an upper end and a lower end and are configured to be complementary connected in a manner with the upper ends adjacent one another and the lower ends adjacent one another, wherein the jacket is of a length greater than a combined length of filaments and at least the collar and the upper ends are configured to retain about the collar and said lower ends are configured to retain about the filaments, and wherein the jacket includes at least one lower opening adjacent a terminal part of the lower ends to readily permit drainage from said jacket by virtue of gravity when upper ends are further displaced from a gravitational surface than the lower ends; and wherein each the panel includes at least one panel opening which extends lengthwise from each the upper end into the lower end terminating at a predetermined distance from a lower end edge and is defined by top edge, bottom edge and side edges, and at least one productivity guide and wear bar which extends transversely through the panel opening and interconnecting the side edges to retain filaments of the brush and serves as a visual productivity guide and wear indicator for filament length. The panels are further equipped with transverse ribs which extend across the upper ends. Side ribs are also provided which extend lengthwise along outer edges of each panel. The lower ends are connected by a junction panel which includes spaced openings to provide drainage yet maintain rigidity and structure.
Another embodiment is directed to a paint brush protective cover for a paint brush having filaments, a collar or ferrule retaining the filaments, which includes a jacket having a hollow interior section, wherein the jacket has a first panel and a second panel removably connectable to the first panel in a manner to be maintained in a predetermined spaced relation to receive the paint brush therebetween, wherein each the panel has an upper end and a lower end and are configured to be complementary connected in a manner with the upper ends adjacent one another and the lower ends adjacent one another, preferably by living hinge, wherein the jacket is of a length greater than a combined length of filaments and at least the collar and the upper ends are configured to retain about the collar and the lower ends are configured to retain about the filaments, and wherein the jacket includes at least one lower opening adjacent a terminal part of the lower ends to readily permit drainage from the jacket by virtue of gravity when upper ends are further displaced from a gravitational surface than the lower ends; and wherein each panel includes at least one panel opening which extends lengthwise from each the upper end into the lower end terminating at a predetermined distance from a lower end edge and is defined by top edge, bottom edge and side edges, and at least one productivity guide and wear bar which extends transversely through the panel opening and interconnecting the side edges to retain filaments of the brush and serves as a visual productivity guide and wear indicator for filament length.
Still another embodiment is directed to a paint brush protective cover for a paint brush having filaments, a collar retaining the filaments and handle. The cover includes a jacket having a hollow interior section, wherein the jacket has a first panel having lateral connecting surfaces and a second panel having lateral connecting surfaces configured to receive the lateral connecting surfaces of said first panel in a manner to removably connect the first panel and the second panel in a manner to be maintained in a predetermined spaced relation to receive the paint brush therebetween. Each panel has an upper end and a lower end and are configured to be complementary connected in a manner with the upper ends adjacent one another and the lower ends adjacent one another, wherein the jacket is of a length greater than a combined length of filaments and at least the collar and the upper ends are configured to retain about the collar and the lower ends are configured to retain about the filaments, and wherein the jacket includes at least one lower opening adjacent a terminal part of the lower ends to readily permit drainage from the jacket by virtue of gravity when upper ends are further displaced from a gravitational surface than the lower ends; and wherein each the panel includes at least one panel opening which extends lengthwise from each the upper end into the lower end terminating at a predetermined distance from a lower end edge and is defined by top edge, bottom edge and side edges, and at least one productivity guide and wear bar which extends transversely through the panel opening and interconnecting the side edges to retain filaments of the brush and serves as a visual productivity guide and wear indicator for filament length. The lower openings on the jacket allow fluid such as paint and solvent to drain adequately and the openings allow air to circulate within the protective cover and about the filaments of the brush.
The invention provides a protective measure for the filaments as well as productivity guide and wear indicator of for the filaments. This deters the filaments from becoming disfigured. Also, the productivity guide and wear bar aids in showing the amount of usage left on the brush.
A handle opening is formed in end surface of the jacket adjacent the upper ends of the panels allowing the handle of the paint brush to protrude out of the jacket. The handle opening is formed between laterally extending connecting surfaces of each of the first and second panels which provide connection of the panels as well as the panels all of which serve to retain about the handle. The first panel's lateral connecting surfaces can be configured to be received inside of the second panel's lateral connecting surfaces and can include a detent surface or other friction fit surface to maintain connection therebetween. A laterally extending tab can be provided on the first panel to aid in separating the panels once connected.
The foregoing and other objects, features, and advantages of the invention will be apparent from the following, more particular, and description of the preferred embodiments of the invention, as illustrated in the accompanying drawing.
BRIEF DESCRIPTION OF THE DRAWINGS
The novel features believed characteristic of the invention are set forth in the appended claims. The invention itself, as well as a preferred mode of use, and advantages thereof, will best be understood by reference to the following detailed description of illustrated embodiments when read in conjunction with the accompanying drawings.
FIG. 1 is an elevated perspective view of the paint brush protective cover of the present invention in a closed position covering the bristles of a paint brush disposed within a paint container with wet media (paint) therein for wet media storage.
FIG. 2 is an elevated perspective view of the paint brush protective cover of the present invention in a closed position.
FIG. 3 is a perspective view of the paint brush protective cover of the present invention in an open position showing an interior thereof.
FIG. 4 is a perspective view of the paint brush protective cover of the present invention in an open position showing an exterior thereof.
FIG. 5 is a back outside plan view of the paint brush protective cover of the present invention in an open position.
FIG. 6 is a side view of the paint brush protective cover of the present invention in an open position.
FIG. 7 is an end view of the paint brush protective cover of the present invention in an open position.
FIG. 8 is a front inside plan view of the paint brush protective cover of the present invention in an open position.
FIG. 9 is an enlarged view of a living hinge portion of FIG. 6 .
FIG. 10 is an enlarged view of a portion of FIG. 5 .
FIG. 11 is an enlarged view of another portion of FIG. 5 .
FIG. 12 is a plan back view of an embodiment of the invention.
FIG. 13 is an enlarged view of a portion of FIG. 12 .
FIG. 14 is an enlarged view of another portion of FIG. 12 .
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to the drawings, a paint brush protective cover is generally designated by the numeral 10 . The paint brush protective cover 10 includes a single jacket 12 made from an anti-stick polymer plastic, such as polystyrene, so that paint will not readily adhere to the jacket 12 . This will aid in the wet storage aspect of the invention.
The jacket 12 can be rectangular in shape and it is contemplated that the jacket 12 can be configured with various shapes and sizes so long as the objectives of the invention can be maintained. The jacket 12 should be sufficient enough size to contain a lower end 13 of the paint brush 14 and at least part of an upper end 15 of the paint brush 14 . By way of example, the jacket 12 is configured for a 2″ brush 14 .
The jacket 12 has a hollow interior section 16 which is defined by a first panel 18 and a second panel 20 of the jacket 12 which are removably connectable to one another in a manner to be maintained in a predetermined spaced relation. Each panel 18 and 20 has an upper end 22 and 24 , respectively, and a lower end 26 and 28 , respectively, which are configured to be complementary connected in a manner with the upper ends 22 and 24 adjacent one another and the lower ends 26 and 28 adjacent one another. Each panel 18 and 20 have transverse exterior ribs 21 and 23 respectively which here are shown as rectangular ribs across upper ends 22 and 24 respectively.
The first panel 18 includes lateral connecting surfaces 30 A and 30 B and can be configured to be received inside of the second panel 20 lateral connecting surfaces 32 A and 32 B. The end 24 includes a retaining member 25 which together with connecting surfaces 32 A and 32 B provide a receiving area for connecting surfaces 30 A and 30 B. By way of example, lateral connecting surfaces 30 A and 30 B fit within retaining members 25 and surfaces 31 A and 31 B or other friction fit surface to improve connection with connecting surfaces 32 A and 32 B. A laterally extending tab 34 can be provided on the first panel 18 to aid in separating the panels 18 and 20 once connected.
The jacket panels 18 and 20 are of a length greater than a combined length of filaments and at least a collar part of the paint brush retaining the filaments and preferably a greater than a combined length of filaments (herein referred to as lower end 13 of the brush 14 ), and collar part of the paint brush retaining the filaments and part of the handle (herein referred to as upper part 15 of the brush 14 ).
Upper ends 22 and 24 are configured to retain about the upper part 15 of the brush 14 and lower ends 26 and 26 are configured to retain about lower end 13 of the brush 15 . Each panel 18 and 20 can include a plurality of laterally spaced elongated openings 36 and 38 , respectively, which extend from respective upper ends 22 and 24 , respectively, and into the lower ends 26 and 28 , respectively, terminating at a predetermined distance “X” short of an edge 40 and 42 of each panel 18 and 20 , respectively. In this regard, it is important to note that the openings 36 and 38 can preferably not extend to a point beyond the length “L” of the filaments of the brush when stored within the jacket as this could permit the filaments to become disfigured by protruding outside of the openings 36 or 38 .
Productivity guide and wear bars 27 and 29 are provided. Openings 36 and 38 extend lengthwise from each the respective upper ends 22 and 24 into the lower ends 26 and 28 respectively terminating at a predetermined distance from a lower end edge 40 and 42 , respectively, and are defined by top edge 60 and 62 , bottom edge 64 and 66 , respectively, and side edges 68 and 70 , respectively. Productivity guide and wear bars 27 and 29 extend across the respective panels 18 and 20 transversely through the panel openings 36 and 38 , respectively, and interconnect the side edges to retain filaments of the brush and serves as a visual productivity guide and wear indicator for filament length as well as lend rigidity and strength to the cover 10 .
The productivity guide and wear bars 27 and 29 aid in retaining the filaments 13 of the brush 14 . The productivity guide and wear bars 27 and 29 can preferably include a curved rib cross section which aid in guiding the filaments 13 , broken and unbroken, into the jacket 12 . The productivity guide and wear bars 27 and 29 provide a good visual indication of the productivity remaining of the brush 14 and aid in retaining filaments 13 within the jacket 12 .
Accordingly, each lower end 26 and 28 of each panel 18 and 20 , respectively, there remains a continuous transverse section to retain the filaments and into which the openings 36 and 38 do not extend. The plurality of openings 36 and 38 are thus located on the jacket 12 for allowing fluid such as paint, solvent, or air to circulate within the protective cover and about the filaments of the brush 14 .
A handle opening 44 is formed in end surface 23 of the jacket 12 adjacent the upper ends 22 and 24 of the panels 18 and 20 allowing the handle H of the paint brush to protrude out of the jacket 12 . The handle opening 44 is formed between laterally extending connecting surfaces 30 A, 30 B and 32 A, 32 B and ends 22 and 24 of each of the first and second panels 18 and 20 all of which serve to retain about the handle H. Sides 32 A and 32 B do not extend the panel 20 to permit flow of paint out of the end of the jacket 12 when closed.
One may open the jacket 12 to expose a hollow interior section 16 . The interior section 16 is where the bristles of the paint brush 14 will be stored in wet or dry manner. The first panel 18 is connected together the second panel by a junction panel 50 and is characterized as a living hinge which is a special type of connector style that is bent while the plastic piece is still warm right out of the mold. Junction panel 50 includes a plurality of lower spaced openings 41 to readily permit drainage and which are separated by transverse portions 43 of panel 50 . Opening the jacket 12 will expose the hollow interior section 16 enabling positioning the paint brush 14 within the jacket 12 and when closed protect the bristle or filament 13 configuration of the brush 14 .
The openings 36 and 38 provide for retention of the bristles while being stored in paint in the case of the jacket 12 being submerged into paint with the brush 14 therein as seen in FIG. 1 . Upon removal, these openings 36 and 38 provide for quick drainage of paint from the jacket 12 so that the jacket 12 can be readily opened without causing a paint spill. After removal of the brush 14 from the jacket 12 , any remaining paint on the jacket 12 should easily drip off. After a job, the brush 14 is cleaned and disposed back in the jacket 12 where the openings 36 and 38 will allow air to circulate therein. The air will allow the bristles of the paint brush 14 dry quickly after being cleaned and prevent mold and mildew from forming inside the jacket 12 .
The protective cover 10 can be preferably be molded such as by injection for example. In this way, the components herein described are integrally formed. While the application has made mention of a preferred use with professional paint brushes, it is conceived that the invention can be employed with various sized brushes, such as artist brushes or the like, wherein the protective cover 10 would be reduced in size to accomplish the intended goal of the invention.
While the invention has been particularly shown and described with reference to preferred embodiments thereof, it will be understood by those skilled in the art that the foregoing and other changes in form and details may be made therein without departing from the spirit and scope of the invention. | A paint brush protective cover for a paint brush includes a jacket which provides for wet media storage and safe transportation. | 0 |
This invention relates to a signature bundle hoist clamp with pivot, and, more particularly, it relates to a clamp for holding a lifting a bundle of signatures which are used in the graphic arts industry.
BACKGROUND OF THE INVENTION
The prior art is already aware of bundle clamps and other means for compressing and holding and lifting bundles of signatures which are arranged with folds therein. These clamps or like devices are commonly employed in the graphic arts industry for lifting bundles and transporting them from one location to another in a printing plant or the like, such as moving the bundles from signature stacker apparatus to signature feeder apparatus where the bundle is separated into its individual signatures and collated into a book or magazine. That is, the stacker apparatus of the prior art normally receives folded sheets or signatures and arranges them in a bundle or stack. End boards or like supports or stiffeners are commonly arranged at opposite ends of the stack, and the stack may be strapped or tied to retain it in a secure and discrete condition. Subsequently, it is desired that the bundle or stack be transported to a feeder apparatus where the bundle is taken apart and the individual signatures or sheets are removed from the bundle for assembly or collating into a book or magazine. However, the stacker has formed the stack or bundle of sheets with the folded edges along one side of the stack, and it may be that the feeder apparatus requires that the folded edges be positioned in an orientation different from that which is presented by the usual hoist or lift truck or like transport apparatus of the prior art. Accordingly, it is necessary that the bundle be rotated so that the folded edges are in the required orientation at the feeder device.
Accordingly, it is an object of this invention to provide apparatus which readily and easily permits the proper orientation of a bundle of signatures at a feeder device or like apparatus or other station located in the printing plant or the like. In accomplishing this objective, the present invention utilizes the bundle clamp already employed in the prior art, and the present invention provides apparatus which permits the bundle of signatures to be readily and firmly secured within the clamp and to be rotatable about the longitudinal axis of the bundles for desired and selective positioning of the folds of the signatures in the bundle.
Prior art examples of sheet stacker, transporting, and feeder apparatus are found in U.S. Pat. Nos. 3,739,924 and 3,825,134 and 3,853,234. These three patents also show the use of a stack or bundle clamp for holding the discrete bundle after the formation and for the transport of the bundle, and the first two patents show an adjustable type clamp. Prior art examples of feeder apparatus are found in U.S. Pat. Nos. 3,416,679 and 3,501,139 and 3,982,749, and these three patents show the apparatus receiving and handling the bundle of sheets to separate the sheets into their individual arrangements and pass them to the feeder or like apparatus. In those instances, the orientation of the fold is of concern, and U.S. Pat. No. 3,501,139 discusses this concern and provides for a particular arrangement for reversing the orientation of the folded edges in the sheets.
Accordingly, the present invention provides an arrangement for a stack or bundle clamp wherein the folded edges can be oriented as desired when they are presented to the feeder or like apparatus.
Other objects and advantages will become apparent upon reading the following description in light of the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side elevational view of the assembly of the clamp and bundle of this invention.
FIG. 2 is an end elevational view of FIG. 1.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
The drawings show a plurality of sheets or signatures 10 positioned in a stack or bundle designated 11, and it will be understood that the stack or bundle is continuous between the shown end sheets or signatures 10, such as extending through the dot-dash line designated 12. The signatures 10 have folded edges or folds 13 and they have open edges or ends 14, and the folds 13 and edges 14 are on opposite sides of the bundle 11, as shown in FIG. 1 so that the folds 13 are shown on the bottom side of the bundle. It will of course be understood that the stacker apparatus has positioned the signatures 10 in the aligned stack as shown, and it is then desired that the stack be compressed and transported to a sheet feeder or to other locations, as desired. Thus the stack 11 has a longitudinal axis 16 and an adjustable clamp 17 is applied to the stack 11 to compress it endwise along the axis 16. The clamp 17 is shown to be in two sections 18 and 19, and they are telescoped together at the mid-portion designated 21, and the clamp has the usual opposite end legs 22 and 23, and thus it is a C-clamp. It will be understood by one skilled in the art that the clamp 17 is adjustable to be capable of having its legs 22 and 23 moved toward and away from each other to thereby engage, compress, and release, all in sequence, the bundle 11. The C-clamps used for this purpose are arranged in well known manners, such as shown in U.S. Pat. No. 3,739,924, and the clamp 17 is capable of being arranged to securely compress the bundle 11 along its axis 16, and conventional controls, such as the control 24 is associated with the clamp 17 and has electric or pneumatic control lines 26 and control buttons 27, all for the purpose of extending and retracting the C-clamp 17 in any conventional manner, and that portion of the arrangement is well known by anyone skilled in the art. Thus the C clamp 17 is extendable and contractable for the purpose of gripping and securing and releasing the bundle 11, in the manner well understood by anyone skilled in the art. Also, a hoist or crane hook 28, forming a hoist connection with the clamp 17, as shown in FIG. 1, may be employed in connection with the clamp 17 for lifting the assembled bundle 11 in clamp 17 and transporting it to a position desired and also for rotating the bundle 11 about its axis 16 in the manner described hereinafter.
The bundle 11 is also shown to be arranged with rectangularly-shaped end boards 29 and 31, and these boards are positioned at opposite ends of the bundle 11, and the folded sheets or signatures 10 are of the same end view size as the boards 29 and 31, as shown in FIG. 2. The clamp legs 22 and 23 are both provided with a combined thrust and axial bearing 32, and the bearings are interposed between the respective clamp legs 22 and 23 and the opposite ends of the bundle 11. Bearing plates 33 and 34 are interposed between each of the two bearings 32 and the two end boards or supports 29 and 31, and these plates 33 and 34 have extended planar surfaces 36 which abut and extend in contact with the outer face or planar surfaces 37 of the respective end boards 29 and 31. Thus the bearing plates 33 and 34 press uniformly and firmly against the end boards 29 and 31 to compress the bundle 11 along its axis 16, and that compression force is presented through the bearings 32 and is resisted by the axial thrust aspects of the bearing 32, such as through the tapered rollers 38 in the bearings 32. Thus, the bearing plates 33 and 34 have hubs 39 which abut the bearings 32 and which extend through the bearings 32 and are secured to the bearings 32 by means of a cap plate 41 and a screw 42, as shown. That is, the hubs 39 have the shoulders 43 which extend over the inner race 44 of the bearing 32 and thus space the bearing plate outer surfaces 44 clear of the clamp leg inner surfaces 46. With this arrangement, the bearing plates 33 and 34 are free to rotate about the longitudinal axes thereof which is coincident with the axis 16 of the bundle 11. As such, the radial aspects of the bearings 32 permit the rotation of the plates 33 and 34, as mentioned, and thus the bundle 11 can be rotated about its axis 16 for positioning the folds 13 in the desired upward or downward direction, according to the requirements of the apparatus handling the bundle 11, such as the aforementioned feeder apparatus.
Accordingly, the bearings 32 are combined thrust and radial bearings and they support the respective plates 33 and 34 for thrust and rotational action relative to the clamp 17, and the plates 33 and 34 are supported clear of the clamp legs 22 and 23 for the rotational action described.
Also, the plates or members 33 and 34 are provided with detents 47 at two diametrically opposite locations on the plate outer surface 44, and the detents 47 are aligned with a detent pin 48 which is retractably mounted in each of the clamp legs 22 and 23 for releasable engagement with a respective one of the detents 47. That is, with the pin 48 engaged with the detent 47 at the upper portion of each plate 33 and 34, as shown in the position in FIG. 1, then the signatures folds 13 are at the bottom of the bundle 11; conversely, when the bearing plates 33 and 34 are rotated to have the diametrically opposite detents 47 engaged by the respective pins 48, then the bundle 11 would be positioned and held in that position to have the folds 13 at the top of the bundle 11. The detent pins 48 may be spring-loaded to be urged toward the respective plates 33 and 34 and thus the pins automatically seat within the detents 47 and are automatically released therefrom, all in accordance with a minimum force of rotation of the bundle 11 about its axis 16. As such, the clamp 17 is provided with the pivot means which incorporates the bearings 32 and the bearing plates 33 and 34.
Therefore, the arrangement is for the side-by-side relationship of the signatures 10 to form the bundle or stack 11 with the end boards 29 and 31 and to compress the bundle along its axis 16 and to render it locatable about that axis by virtue of the pivot mechanism which includes the bearing 32. Also, inter-engaging alignment means in the form of the detent 47 and pin 48 are interposed between the clamp 17 and the bearing plates 33 and 34, all for orientation of the folds in the bundle 11. The plates 33 and 34 are mounted permanently with the bearings 32 which are permanently mounted in the clamp legs 22 and 23.
The common axis of the two bearings 32 is spaced from the C-clamp intermediate portion between the legs 22 and 23 such that the bundle 11 can be rotated about the axis 16 and clear the intermediate C-clamp portion. That is, there is a space 49 between the bundle 11 and the intermediate portion of the C-clamp 17, and the outermost limit of the bundle 11, such as the lower right hand corner 51 in FIG. 2, will be rotatable past the C-clamp intermediate portion, all as provided by the arrangement of the location of the bearings 32 and the size of the bundle 11 and the space 49, as mentioned. | A signature bundle hoist clamp with a pivot for rotating the bundle about its longitudinal axis to thereby selectively position the folds in the signature at either the top or bottom of the bundle, for instance. The clamp includes adjustable legs, and a bearing plate is rotatable on each of the legs and is presented toward the bundle for compressing the bundle and permitting the rotation mentioned. A combined thrust and radial bearing is interposed between the clamp legs and the bearing plate for the compression and rotation mentioned, and a releasable stop pin engages the bearing plate for positioning the bundle in the selected position mentioned. The entire assembly is arranged with a hoist. | 1 |
This application is a continuation of application Ser. No. 09/014,945 filed Jan. 28, 1998, now U.S. Pat. No. 6,030,415 and also claims benefit of Provisional No. 60/036,518 filed Jan. 29, 1997.
FIELD OF THE INVENTION
The present invention is directed to an intraarterial prosthesis, a modular stent-graft, for repair of abdominal aortic aneurysm (“AAA” herein).
BACKGROUND OF THE INVENTION
An intraarterial prosthesis for the repair of AAAs (grafts) is introduced into the AAA through the distal arterial tree in catheter-based delivery systems, and is attached to the non-dilated arteries proximal and distal to the AAA by an expandable framework (stents). An intraarterial prosthesis of this type has two components: a flexible conduit, the graft, and the expandable framework, the stent (or stents). Such intraarterial prosthesis used to repair AAAs is named stent-graft. AAAs typically extend to the aortic bifurcation of the ipsilateral femoral artery and the contralateral femoral artery. There is rarely any non-dilated aorta below the aneurysm, and thus the distal end of the graft must be implanted in the iliac arteries, and for the graft to maintain prograde in-line flow to the legs and arteries of the pelvis, it must also bifurcate. Currently available stent-grants fall into two categories. The first category of stent-grafts are those in which a preformed bifurcated graft is inserted whole into the arterial system and manipulated into position about the AAA. This is a unitary stent-graft. The second category of stent-grafts are those in which a bifurcated graft is assembled in situ from two or more stent-graft components. This latter stent-graft is referred to as a modular stent-graft.
SUMMARY OF THE INVENTION
The present invention is directed to a modular stent-graft comprising multi-components. The modular stent-graft of the present invention eliminates or avoids the main drawbacks common to the currently available modular stent-grafts for repair of AAAs. Stent-grafts are inserted into the AAA through the femoral arterial system. The graft must bridge the AAA and form a leak-proof conduit between the aorta and the femoral arteries. The surgeon can only view the operation by X-ray techniques and yet the surgery is performed in a three-dimensional environment. This is a demanding regime and requires a trained and skilled surgeon.
The main drawbacks common to the current modular stent-grafts are:
(1) The connection site between the stent-graft components is prone to leakage and a separation of the components which allows blood to leak directly into the AAA restoring the potential for rupture. If the AAA ruptures, the result is frequently the death of the patient.
(2) The connection site on the first stent-graft component is often difficult to catheterize prior to introduction of the second stent-graft component. The necessary instrumentation required to insert catheters and carry out the repair of the abdominal aneurysm can dislodge mural thrombus in the AAA. The dislodged mural thrombus is carried in the blood flow through the femoral arteries to small distal arteries causing blockage and tissue necrosis.
The modular stent-graft of the present invention consists of three stent-graft components. The first stent-graft component resembles a pair of shorts with the trunk proximal and the two legs or docking sites distal. The second and third stent-graft components are tubes of almost uniform diameter that extend from the primary stent-graft component docking sites, through the AAA, to the femoral arteries. The completed modular stent graft bridges the AAA from the abdominal aorta to the femoral arteries. The proximal ends of the second and third stent-graft components, i.e., ends nearest the aorta, are inserted into the docking sites of the primary stent-graft. The second stent-graft component is inserted through the ipsilateral arteries to the ipsilateral docking site of the primary stent-graft component. The second stent-graft is also referred to as the ipsilateral extension. The third stent-graft component is inserted through the contralateral arteries to the contralateral docking site through the bell-bottom portion of the primary stent-graft component. The third stent-graft is also referred to as the contralateral extension.
The modular stent-graft of the present invention has a number of distinguishing elements. The stents that hold the two docking sites open are at different levels and are of different sizes. On the ipsilateral docking site, the stent is within the docking site. With regard to the contralateral docking site, the stent is within a wider distal segment, the bell-bottom segment below the contralateral docking site.
Because the distal stents of the primary stent-graft component are at different levels, one below the other, they occupy different segments of the delivery system. Since the stent-graft components are delivered to the AAA though a narrow catheter, they must be reduced to the smallest possible diameter to effect and ease delivery. By separating the stent-graft into three components, the necessary stents can be arranged at different levels permitting them to be as large as possible. Since the distal stents can be larger in a modular system than in a unitary system, the distal orifice of the ipsilateral and contralateral docking site can be large and thus easier to catheterize for the delivery. This is only important on the contralateral side, that is, the side with the contralateral docking site. On the ipsilateral side, that is, the side with the ipsilateral docking site, catheters can be introduced over the same guide wire that was used to introduce the first stent-graft component through the arterial system to the AAA. In practice, the distal orifice of the contralateral docking site can be at least as large as the trunk of the primary stent-graft component. The first stent-graft component 12 and the second and third stent-graft components 14 and 16 can be made of the same different biologically inert graft and stent material, such as biologically inert knit or woven fabric, or membrane material, such as PTFE membrane material, and springy material, such as stainless steel or titanium.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a cross-sectional view of the modular stent-graft of the present invention implanted to repair an abdominal aortic aneurysm;
FIG. 2 is a front perspective view of the first stent-graft component of the modular stent-graft of FIG. 1;
FIG. 3 is a cross-sectional view of the first stent-graft component of FIG. 2;
FIG. 4 is a top fragmentary cross-sectional view of the stent-graft of FIG. 1;
FIG. 5 is an enlarged fragmentary cross-sectional view of the connection between the first stent-graft component and the third stent-graft component of the stent-graft of FIG. 1;
FIG. 6 is a cross-sectional view of the second stent-graft component of the modular stent-graft of FIG. 1;
FIG. 7 is a front perspective view of an alternative embodiment of the first stent-graft component of the modular stent-graft of the present invention;
FIG. 8 is a cross-sectional view of a second alternative embodiment of the first stent-graft component of the modular stent-graft of the present invention; and
FIG. 9 is a front perspective view of a third alternative embodiment of the first stent-graft component of the modular stent-graft of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
Referring to FIG. 1, the modular stent-graft 10 of the present invention is illustrated implanted to repair an abdominal aorta aneurysm 28 . The modular stent-graft 10 comprises a first stent-graft component 12 having a proximal end 13 A and a distal end 13 B, second stent-graft component 14 , often referred to as the ipsilateral extension, and a third stent-graft component 16 , often referred to as the contralateral extension. The three components comprise sheaths or grafts 41 , 21 and 23 containing self-expanding stents (not shown in FIG. 1 ). The proximal end 13 A of the trunk 40 of the first stent-graft component 12 is implanted in the proximal implantation site 30 in a non-dilated portion of the abdominal aorta 22 . The proximal end 36 of the second stent-graft component, or ipsilateral extension, is connected to the first stent-graft component at the ipsilateral docking site 18 . The proximal end 37 of the third stent-graft component 16 , or contralateral extension, is connected to the first stent-graft component at the contralateral docking site 20 . The distal end 38 of the second stent-graft component is implanted in the undilated portion of the ipsilateral iliac artery 24 at the ipsilateral distal implantation site 32 . The distal end of the third stent-graft component, or contralateral extension, is implanted in a non-dilated portion of the contralateral iliac artery 26 at contralateral distal implantation site 34 , as will be described herein. The contralateral leg 15 B of the first stent-graft component terminates in a bell-bottom 42 . Bell-bottom aids in the surgical implantation and manipulation of the modular stent-graft in the aorta and the aneurysm 28 as will be described below.
The ipsilateral catheter guide wire 80 is shown coming up from the ipsilateral arteries (the isilatoral femoral artery and ipsilateral iliac artery) into the ipsilateral extension through the ipsilateral docking site and out through the proximal end 13 A of the trunk 40 . The contralateral catheter guide wire 82 is shown extending up from the contralateral femoral artery through the contralateral iliac artery and through the contralateral extension 16 through the contralateral docking site 20 and out through the proximal end 13 A of the trunk 40 . Normally, both guide wires are left in until the completion of the operation. After the modular stent-graft has been successfully implanted to repair the abdominal aortic aneurysm, the guide wires are removed. In the preferred embodiment, the ipsilateral catheter guide wire 80 is first inserted to permit the delivery of the first stent-graft component and the ipsilateral extension into the AAA. The contralateral catheter guide wire 82 is inserted from the contralateral iliac artery 26 into the contralateral docking site 20 of the first stent-graft component. As mentioned above, the surgeon is viewing the three-dimensional environment of the AAA with a two-dimensional X-ray screen. The large bell-bottom 42 of the first stent-graft component eases the surgeon's task in successfully snaking the guide wire 82 up into the bell-bottom 42 and into the contralateral docking site 20 . Obviously when the first guide wire 80 is inserted, the surgeon is concerned with having the guide wire come out of the ipsilateral iliac artery 24 through the AAA into the abdominal aorta 22 . Without the bell-bottom 42 below the contralateral docking site 20 , it would be very difficult, and in many instances impossible, to successfully snake the contralateral catheter guide wire 82 into the contralateral docking site 20 of the first stent-graft component.
Referring to FIGS. 2 and 3, the first stent-graft component 12 of the modular stent-graft 10 comprises a trunk 40 at the proximal end 13 A of the first stent-graft component and ipsilateral leg 15 A and contralateral leg 15 B at the distal end 13 B of the first stent-graft component. The distal end of the ipsilateral leg 15 A has a constricted portion 62 . The contralateral leg 15 B has a constricted portion 64 at approximately the same level as constricted portion 62 . A radioopaque marker 66 is placed on the first stent-graft component in the constricted portion 64 adjacent the constricted portion 62 , as shown in FIG. 2 . This marker aids the surgeon in positioning the proximal stents of the ipsilateral and contralateral extensions. The first stent-graft component is delivered into the aorta aneurysm 28 via a conventional stent-graft catheter delivery system, such as disclosed in U.S. Pat. Nos. 4,580,568; 4,655,771; 4,830,003; 5,104,404; and 5,222,971. The modular stent-graft has three self-expanding stents: a proximal trunk stent 48 , situated within the first stent-graft component at the proximal end 13 A; an ipsilateral trunk stent 50 , positioned within the first stent-graft component near the distal end 13 B of the ipsilateral leg 15 A; and a bell-bottom stent, located within the bell-bottom 42 at the distal end 13 D of the contralateral leg 15 D. These are self-expanding stents of the conventional type, such as disclosed in U.S. Pat. Nos. 4,580,568; 4,655,771; 4,830,003; 5,104,404; and 5,222,971. My self-expanding stent disclosed in U.S. patent application Ser. No. 08/582,943 can be used.
The stents employed in the present invention are self-expanding and thus are constricted in the catheter delivery system. Since the first stent-graft component delivered to the aorta aneurysm has three stents at different levels, the graft (the envelope of the first stent-graft component) and stents can be quite large since they can be contracted to a very small diameter for easy delivery of the stent-graft through the ipsilateral arteries by conventional means. If two or more stents were at the same level, it would not be possible to contract the first stent-graft component to the same degree without reducing the size of the distal stents. The first stent-graft component 12 is delivered through the AAA until the proximal end 13 A of the first stent-graft component is positioned within the proximal implantation site 30 of the aorta 22 . The delivery system slowly releases the first stent-graft component allowing the proximal trunk stent 48 to self-expand to form a union between the inner wall of the undilated portion, i.e., healthy portion, of the aorta 22 and the outer wall of the proximal end of the first stent-graft component 12 . The surgeon observes this manipulation by X-ray observation. As the delivery system is withdrawn, leaving the first stent-graft component in the aneurysm 28 , the ipsilateral trunk stent 50 expands and then the bell-bottom stent 52 expands to form the bell-bottom. The stents 50 and 52 keep the distal ends of the legs 15 A and 15 B open for insertion of the second and third stent-graft components 14 and 16 . The ipsilateral catheter guide wire 80 utilized to guide the first stent-graft component through the ipsilateral iliac artery 24 and through the aorta aneurysm 28 to the undilated portion of the aorta 22 remains behind as a guide for the insertion, connection, and implantation of the second stent-graft component 14 .
The delivery system containing the contracted second stent-graft component is guided back to the AAA using the ipsilateral guide wire 80 in the same manner as the guide wire was used to implant the first stent-graft component. As shown in FIG. 6, the second stent-graft component or ipsilateral extension 14 is comprised of a tubular sheath 21 with a plurality of self-expanding stents, the proximal ipsilateral extension stent 54 , the distal ipsilateral extension stent 55 and supporting stents 60 . The stents are self-expanding and are contracted when inserted into the delivery system. Once the delivery system has correctly positioned the ipsilateral extension in the modular stent-graft and is withdrawn, the stents are sequentially expanded as the delivery system is withdrawn.
Referring to FIGS. 1 and 4, the proximal end 36 of the ipsilateral extension 14 is inserted into the ipsilateral docking site 18 . As the delivery system is withdrawn, the proximal ipsilateral extension stent 54 expands, compressing the tubular sheath 21 between the ipsilateral trunk stent 50 and the proximal ipsilateral extension stent 54 . The internal diameter of the ipsilateral trunk stent 50 is greater than the internal diameter opening of the restriction 62 , causing a narrow waist 70 to form in the sheath 21 as the proximal ipsilateral extension stent 54 expands. This physically locks or secures the ipsilateral extension 14 to the ipsilateral leg 15 A to prevent the ipsilateral extension from slipping out or being pulled out of the first stent-graft component. As the delivery system is fully withdrawn, the distal ipsilateral extension stent 55 expands compressing the sheath 21 against the interior wall of the ipsilateral femoral artery 24 at the ipsilateral distal implantation site 32 .
After the surgeon confirms that the ipsilateral extension has been successfully implanted into the ipsilateral iliac artery 24 , a contralateral catheter guide wire 82 is then inserted into the AAA through the contralateral iliac artery 26 . As mentioned above, the bell-bottom 42 of the first stent-graft component aids the surgeon in snaking the guide wire into the contralateral docking site 20 . After the guide wire has been successfully positioned, the delivery system containing the compressed contralateral extension 16 , which for all intents and purposes is identical to the ipsilateral extension shown in FIG. 6, is guided along the guide wire 82 so that the proximal end 37 of the contralateral extension is positioned within the contralateral docking site 20 . The proximal end of the contralateral extension is positioned in the docking site so that the first proximal contralateral extension stent 56 is positioned above or proximal to the constriction 64 and the second proximal contralateral extension stent 58 is positioned below or distal to the constriction 64 . As the delivery system is withdrawn, stents 56 and 58 , which are self-expanding, expand forcing the sheath 21 of the contralateral extension to expand out to compress the sheath against the inner walls of the contralateral docking site 20 . Since the outer diameter of the expanded stents 56 and 58 are larger than the inner diameter of the constriction 64 , a narrow waist 72 is created in the sheath 21 . This physically locks or secures the proximal end 37 of the contralateral extension into the docking site 20 of the first stent-graft component. After the surgeon confirms that the proximal end of the contralateral extension has been successfully connected to the contralateral docking site, the surgeon manipulates the distal end 39 of the contralateral extension into the contralateral distal implantation site 34 of the contralateral iliac artery 26 . Once this positioning has been completed, the surgeon carefully withdraws the delivery system to permit the distal contralateral extension stent (not shown) to expand and compress the outer wall of the contralateral extension sheath 21 against the inner wall of the contralateral femoral artery. When the surgeon confirms that the contralateral extension has been successfully implanted, the contralateral catheter guide wire is then withdrawn. At this point the modular stent-graft has been successfully implanted to repair the AAA, a repair that not only protects the life of the patient but also enhances the quality of the patient's life, since the aneurysm has been shunted out of the patient's circulatory system and no longer functions as a hydraulic accumulator.
The radioopaque marker 66 in the constriction 64 of the contralateral docking site 20 functions as a marker for the surgeon as he observes the manipulation of the various components during the operation. The marker permits the surgeon to easily locate the positioning of the proximal ipsilateral extension stent and the proximal contralateral extension stent 54 , 56 respectively, with respect to the restrictions 62 , 64 respectively.
Referring to FIG. 7, an alternative embodiment of the first stent-graft component 12 A of the present invention is illustrated wherein the bell-bottom 42 is angled towards the contralateral iliac orifice, making it easier to guide the contralateral catheter guide wire 82 into the contralateral docking site 20 , as described above. In all other respects, the first stent-graft component is identical to the stent-graft component 12 described above. The stents 48 , 50 and 52 are shown in phantom.
Referring to FIG. 8, a second alterative embodiment of the first stent-graft component 12 B of the present invention is illustrated. The ipsilateral docking site 18 A is free of an ipsilateral trunk stent which is contained in the first stent-graft component 12 described above. However, the contralateral docking site 20 A has a contralateral trunk stent 51 with a series of longitudinal struts 53 extending distally or downwardly from the stents 51 biased to create a conical section with respect to cone 44 of the first stent-graft component. In all other respects, the first stent-graft component 12 B is identical to the first stent-graft component 12 described above.
When the alternative embodiment first stent-graft component 12 B is utilized to form a modular stent-graft, the proximal end 36 of the ipsilateral extension 14 is positioned slightly above the restriction 62 so that when the proximal ipsilateral extension stent 54 expands, it expands the outer wall of the sheath 21 of the ipsilateral extension against the inner wall of the ipsilateral docking site 18 A to seal the ipsilateral extension to the first stent-graft component 12 B.
The outer diameter of the proximal ipsilateral extension stent is greater than the inner diameter of the constriction 62 causing the sheath 21 of the ipsilateral extension to form a narrow waist (not shown), thus locking and securing the proximal end of the ipsilateral extension to the ipsilateral docking site 18 A to prevent the extension from slipping out or being pulled out of the first stent-graft component 12 B. The cone 44 acts in the same manner as the bell-bottom 42 to give the surgeon a greater target area to locate the contralateral catheter guide wire into the contralateral docking site 20 A. When the first stent-graft component 12 B is in the delivery system, it is compressed and struts 53 are aligned parallel to each other and adjacent to each other. When the delivery system is withdrawn after the first stent-graft component has been implanted into the proximal implantation site 30 , the struts 53 expand outwardly to expand the envelope 45 of the cone 44 . The struts bow out at the juncture of the constriction 64 A so as to help form the narrow waist 72 A at the proximal end 37 of the contralateral extension 16 . After the contralateral catheter guide wire has been positioned within the contralateral docking site 20 A, the proximal end 37 of the contralateral extension 16 is positioned within the docking site. The delivery system is slowly withdrawn, allowing the proximal contralateral extension stent 56 to expand, compressing the sheath 21 of the extension between the inner side of the contralateral trunk stent 51 and the outer side of the first proximal contralateral extension stent 56 . The narrow waist 72 A formed in the sheath 21 locks or secures the proximal end 37 of the contralateral extension to the contralateral docking site 20 A to prevent the extension from slipping out or being pulled out of the docking site.
Referring to FIG. 9, a third alternative stent-graft component 12 C is illustrated which is identical to the first stent-graft component 12 described above, with the exception that ipsilateral docking site 18 B of this first stent-graft component does not contain an ipsilateral front stent. In contrast, in this first stent-graft component 12 C, a flexible bracer 78 is located within the component to prevent longitudinal collapse of the ipsilateral leg 15 A during implantation into the proximal implantation site 30 . Alternatively, longitudinal collapse of the ipsilateral leg 15 A can be prevented in the first stent-graft component 12 C described above by attaching ipsilateral leg 15 A to contralateral leg 15 B by struts attached between the two legs, a membrane attached to the two legs, or by sewing the two legs together (not shown). | A system for repairing body lumens including a modular graft and a method for deploying the graft within the body lumen. The modular graft includes a first component having first and second leg portions which mate with second and third graft components, respectively. The second leg portion has a bell bottom shape. The modular graft further includes expandable members which aid in implanting the modular graft as well as facilitates the mating of its components. In order to repair the body lumen, the first component is placed at the repair site and thereafter, the first and second legs are advanced to the repair site and attached to the first component. | 0 |
BACKGROUND OF THE INVENTION
Gable top cartons are formed from a unitary blank of paperboard material that is scored and folded to define a bottom wall, an upstanding side wall enclosure extending from the bottom wall and a gable top. The bottom wall of the typical prior art gable top carton is square, while the side wall enclosure typically is defined by two opposed pairs of parallel side wall extending upwardly from and connected to the bottom wall. However, the prior art does include gable top cartons having circular bottom walls with a side wall enclosure that gradually transforms from a generally cylindrical bottom to a rectangular top.
The top of the prior art gable top carton is defined by a pair of opposed rectangular roof panels that are articulated to the side walls and converge toward one another. The rectangular roof panels are sealed to one another along edge regions remote from the side walls. The gable top of the prior art carton is defined further by triangular pour panels that are articulated from the remaining two side walls and also converge toward one another. Each triangular pour panel is connected to both rectangular roof panels by triangular web panels that extend therebetween. The prior art gable top carton is closed by initially rotating the triangular pour panels toward one another and subsequently rotating the rectangular roof panels toward one another for sealing engagement along the top edge regions thereof. Approximately half of the top edge seal of the prior art gable top carton defines a permanent seal, while the remaining portion defines a releasable seal. The releasable portions of the top seal can be separated from one another to enable the associated pour panel to be folded outwardly to define a pour spout for accessing the material stored in the carton. The pour panel ca be folded back inwardly to at least partly reseal the carton, and can be reopened for repeated access to the contents of the carton as needed.
Prior art gable top cartons have achieved tremendous commercial success and are widely employed for storing drinkable liquids, such as milk, juices and the like. Prior art gable top cartons also are used for storing other flowable materials, such as snack foods, cereals, pet foods, detergents and many other liquid or granular products. Despite this continued and substantial commercial success, it is desirable to further improve gable top cartons. In particular, many consumers find the initial opening of gable top cartons to be difficult. In this regard, the initial folding back of the triangular web panels and adjacent portions of the rectangular roof panels typically can be carried out easily by most consumers. However, the subsequent initial outward folding of the pour panel requires a separation of edge regions that had previously been sealed to one another. This separation normally is facilitated by careful application of adhesive, abhesive and/or coatings. However, many consumers still find this initial separation to be difficult. Additionally, many consumers who are adept at opening gable top cartons find significant variance from one carton to the next in view of the tendency of some paperboard material to delaminate. Thus, in some instances, the forces normally applied to effect the initial opening of a carton may cause a local delamination of paperboard material with corresponding opening difficulties and the creation of an inefficient pour spout.
In addition to problems associated with the initial opening of prior art gable top cartons, the resealing of such cartons may not be sufficiently effective to ensure freshness of the commodity stored therein or to prevent leaks during the shaking required for some beverages, such as orange juice. This may be particularly true for prior art gable top cartons that were at least partly damaged by the paperboard delamination during opening.
Consumers who have experienced or perceived problems with the prior art gable top cartons may resort to the available blow molded plastic containers. However, plastic containers present an environmental risk as compared to the paperboard gable top cartons that are formed substantially from biodegradable materials. Additionally, blow molded plastic containers require additional complex structure for tamper resistance or tamper evidence. The typical tamper resistant seal means for plastic containers may include a cap having an integrally formed frangible ring that is locked to the container and must be separated during the initial opening, a shrink-wrap overlay of plastic material and/or foil or paperboard seals disposed over the opening and beneath a removable plastic cap. The dexterity that is required to effect the initial opening of these tamper resistant plastic containers often is greater than the problems associated with the initial opening of the prior art gable top carton.
Recently there have been some attempts to combine the technology of gable top cartons with the openings of blow molded plastic containers. In particular, separate plastic pour spouts have been incorporated into the rectangular roof panels of gable top cartons. A removable cap is selectively attachable to the plastic pour spout in the rectangular roof panel for sealing the contents of the carton. However, this combination offers the potential for tampering, and consequently the above described tamper prevention means must be incorporated into the pouring spout and/or cap on the rectangular roof panel. As explained above, the known tamper prevention means can create very substantial opening difficulties for many consumers.
A gable top carton with a snap lock plastic cap and a mateable plastic spout on a pour panel of the gable top is shown in copending U.S. Patent Application Ser. No. 405,134, entitled "GABLE TOP CARTON WITH RESEALABLE POUR SPOUT", which was filed by Nestor A. Anderson and is assigned to the assignee of the subject invention. The disclosure of this copending application is incorporated herein by reference.
In view of the above, it is an object of the subject invention to provide a gable top carton having an easy opening and resealable pouring spout.
It is another object of the subject invention to provide a gable top carton that is tamper resistant and provides evidence of tampering.
It is another object of the subject invention to provide a gable top carton that does not require separate structure for tamper resistance or tamper evidence.
SUMMARY OF THE INVENTION
The subject invention is directed to a gable top carton having a threaded plastic pour spout incorporated into a pour panel thereof and a plastic cap threadedly engaged with the plastic pour spout. The subject invention is further directed to an assembly of components comprising a paperboard blank for forming a carton, a plastic pour spout selectively engageable with the blank and a plastic cap selectively engageable with the pour spout.
The carton of the subject invention comprises a unitary piece of paperboard material that may be coated on at least one side thereof to provide the necessary degree of moisture impermeability for the intended end use. The paperboard material may further be coated on an external side to facilitate imprinting of product indicia and to provide protection during filling, storage and distribution. The carton is formed to include a bottom wall, an upstanding side wall enclosure connected to and extending from the bottom wall and a gable top. The gable top includes a pair of opposed substantially isosceles triangular pour panels hingedly connected to the upstanding side wall enclosure and converging toward one another. One of the pour panels includes a aperture extending therethrough.
A closure assembly is mounted to the triangular pour panel with the aperture. The closure assembly comprises a base with a substantially cylindrical pour spout. The base may further be defined by a mounting flange adhered in face-to-face relationship with portions of the triangular pour panel surrounding the aperture therein. The mounting flange may be disposed either interiorly or exteriorly on the triangular pour panel, depending at least in part on the particular combination of coating materials on the interior and exterior of the carton and on the material being stored in the carton. Portions of the cylindrical pour spout remote from the mounting flange include an array of threads. A cap is threadedly engaged with the cylindrical pour spout either exteriorly or interiorly, with the preferred embodiment employing an external cap to ensure a larger surface area for gripping by the consumer, thereby facilitating the manual opening of the cap
The gable top of the subject carton is further defined by a pair of opposed rectangular roof panels that converge toward one another in generally overlying relationship to the triangular pour panels of the carton. The rectangular roof panels are sealed to one another along edge regions remote from the upstanding side wall enclosure of the carton. The sealing of the triangular roof panels in overlying relationship to the pour panels functions as a tamper prevention means and tamper evidence means for the carton. In particular, the plastic cap of the carton can not be removed until the roof panels are initially separated from one another to access the plastic cap and enable its threaded removal. This initial separation of the roof panels is substantially identical to the first step in the opening of a conventional prior art gable top carton as explained above. This part of the opening process for prior art gable top cartons had not presented a problem to consumers, and therefore would not be anticipated to present problems in the context of the subject carton. Conversely, the subject carton avoids the subsequent folding out of the pour panel which had presented problems to some consumers employing the prior art gable top cartons.
It will also be appreciated that the tamper resistance provided by the sealed roof panels avoids the need to employ a cap having a frangible locking ring, a separate shrink wrap over the cap or a separate sealing foil secured over the plastic pouring spout. However, the inner top surface of the cap may have a foil lining to provide an enhanced gas and vapor barrier, and in particular to minimize transmission of oxygen. The subject design offers certain manufacturing efficiencies as well. In particular, it is unnecessary to provide the special adhesives, abhesives or coatings that had been required to facilitate the folding out of the pour panel during the initial opening of the prior art carton. Rather, the triangular web panels articulated to the pour panel remain permanently sealed to the top edge regions of the rectangular roof panels. Additionally, the threaded interconnection of the cap to the pour spout of the subject container can provide an efficient sealing that can enhance the life of certain materials that may be stored in the carton.
As noted above, the subject invention is further directed to an assembly of components for forming the above described container. The components of this assembly comprise a blank formed from a unitary piece of paperboard material that is scored to define the respective panels of the above described carton. One of the two isosceles triangular pour panels of the subject blank is provided with an aperture formed therethrough or with an array of perforations to facilitate the creation of an aperture of a selected shape. The assembly of components further includes the above described base having a mounting flange defining an area greater than the area of the hole in the pouring panel and a generally cylindrical pour spout extending unitarily from the mounting flange and defining a cross section substantially identical to the cross section of the aperture in the pouring panel. The cylindrical pour spout preferably comprises an array of external threads thereon, but may additionally or alternatively be provided with an array of internal threads. The assembly of components of the subject invention further comprises a cap that is threadedly engageable with the pour spout. Preferably, the cap is defined by a knurled exterior surface and an array of internal threads that are engageable with the threads of the pour spout.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a top plan view of a blank in accordance with the subject invention.
FIG. 2 is a top plan view of the combined pour spout and cap of the subject invention.
FIG. 3 is a cross-sectional view taken along line 3--3 in FIG. 2.
FIG. 4 is a cross-sectional view similar to FIG. 3 but showing the cap and pour spout in an exploded condition.
FIG. 5 is a front elevational view of the erected carton of the subject invention.
FIG. 6 is a perspective view of the carton at a first stage during opening.
FIG. 7 is a perspective view of the opened carton with the cap thereof disengaged and in an orientation for pouring material therefrom.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
A blank for forming the carton portion of the container of the subject invention is identified generally by the numeral 10 in FIG. The blank 10 is formed from a unitary piece of paperboard material. The paperboard may be coated or laminated to enhance the protection of the material stored in the container formed from the blank 10, and/or to provide an enhanced surface for printing product identifying indicia thereon. Appropriate coatings may be disposed on one or both sides of the blank 10.
The blank 10 is provided with an array of score lines which divide the panel into a plurality of hingedly connected panels. Adjacent panels can be folded relative to one another and about the score lines to form a gable top carton, as explained herein. In this regard, the blank 10 includes a rectangular first side panel 12, a rectangular second side panel 14, a rectangular third side panel 16, a rectangular fourth side panel 18 and a side seal panel 20, all of which are consecutively articulated to one another along parallel fold lines 13, 15, 17 and 19 respectively.
The first side panel 12 is further defined by an edge 11 of the blank 10 which extends parallel to the fold line 13. The first side panel 12 is further defined by a first bottom fold line 21 and a first top fold line 22 which extend generally parallel to one another and which connect the edge 11 of the blank 10 to the fold line 13 of the first side panel 12. As will be explained further below, the portion of the first side panel 12 adjacent to the edge 11 will be securely adhered to the side seal panel 20 on the carton formed from the blank 10.
A first bottom panel 23 is articulated to the first side panel 12 along the first bottom fold line 21. The first bottom panel 23 is of approximately rectangular configuration and is further defined by fold line 24 which extends generally colinearly from the fold line 13 and parallel to the edge 11 of the blank.
A rectangular first top panel 25 is articulated to the first side panel 12 along the first top fold line 22. The first top panel 25 will define one of the two rectangular roof panels on the carton erected from the blank 10. The first top panel 25 is of generally rectangular configuration, and is further defined by fold line 26 which extends colinearly from the fold line 13 and parallel to the edge 11. Additionally, the first top panel 25 is further defined by fold line 27 which extends parallel to the fold line 22 and between the edge 11 of the blank 10 and the fold line 26. The first top panel 25 is further characterized by a diagonal score line 28 which extends from the intersection of fold lines 22 and 26 to a point approximately midway along the fold line 27. The score line 28 effectively defines a corner of the roof panel on the carton that can be folded back to provide access to a pour spout used with the carton erected from the blank 10, as explained and illustrated below.
A generally rectangular first top seal panel 29 is hingedly connected to the first top panel 25 along fold line 27. The side of the first top seal panel 29 that will face inwardly on the carton erected from the blank 10 may be provided with an appropriate heat seal for securely attaching the first top seal panel 29 to other top seal panels as explained herein. The first top seal panel 29 is further defined by the edge 11 of the blank 10 and by fold line 30 which extends parallel to the edge 11 and generally colinearly from the fold line 26.
The second side panel 14 is further defined by second bottom fold line 31 and second top fold line 32 which extend substantially parallel to one another and which connect the fold lines 13 and 15. A second bottom panel 33 is articulated to the second side panel 14 along the second bottom fold line 31. The second bottom panel 33 is of isosceles triangular configuration and is further defined by fold lines 34 and 36 which converge toward one another from opposed ends of the second bottom fold line 31. A triangular web panel 38 is articulated to the second bottom pane 33 along fold line 34 and is further articulated to the first bottom panel 23 along fold line 24. A substantially identical bottom web panel 40 is articulated to the second bottom panel 33 along the fold line 36, and is further defined by a fold line 44 which extends substantially colinearly from the fold line 15.
A second top panel 45 is articulated to the second side panel 14 along fold line 32. The second top panel 45 also is of substantially isosceles triangular configuration, and is defined by fold lines 46 and 47 which converge toward one another from the opposed ends of the fold line 32. The second top panel 45 will define the pour panel on the carton erected from the blank 10. A circular array of perforations identified by the numeral 48 is defined in the second top panel 45. More particularly the circular array of perforations 48 defines a circular area that can be selectively depressed from the second top panel 45 to enable use of a plastic pour spout as explained further below. A circular cutout may be defined in place of the circular perforation array 48, thereby obviating the need to remove a portion of paperboard material at the time of use by the customer.
Triangular web panels 49 and 50 are articulated to the second top panel 45 along fold lines 46 and 47 respectively. The web panel 49 is further defined by the fold line 26 and by a fold line 52 which extends substantially colinearly from the fold line 27. The web panel 50 is further defined by fold line 54 which extends colinearly from the fold line 52 and by fold line 56 which extends colinearly from fold line 15 to intersect the fold line 54. A second top seal panel 59 is articulated to the web panels 4 and 50 along fold lines 52 and 54 respectively. The second top seal panel 59 is further defined by fold line 30 and by fold line 60 which extends colinearly from the fold line 56. Unlike prior art gable top cartons, the second top seal panel 59 may be securely adhered to other top seal panels, including the first top seal panel 29.
The third side panel 16 is further defined by a third bottom fold line 61 and a third top fold line 62 which extend generally parallel to one another and between the fold lines 15 and 17. A generally rectangular third bottom panel 63 is articulated to the third side panel 16 along fold line 61. The third bottom panel 63 is articulated to the web panel 40 along fold line 44, and is further defined by fold line 64 which extends substantially colinearly from the fold line 17.
A third top panel 65 is articulated to the third side panel 16 along fold line 62. The third top panel 65 is generally rectangular, and will define one of the two rectangular roof panels on the carton erected from the blank 10. In particular, as will be explained further below, the third top panel 65 will converge toward the first top panel 25 to define a pair of opposed converging rectangular roof panels which overlay the pour panel defined by the second top panel 45. The rectangular third top panel 65 is articulated to the web panel 50 along fold line 56. The third top panel 65 is further defined by fold line 66 which extends colinearly from the fold line 17 and by fold line 67 which extends parallel to the fold line 62 and between the fold lines 56 and 66. The third top panel 65 additionally is defined by a diagonal score line 68 which extends from the intersection of fold lines 56 and 62 to a location approximately midway along the fold line 67. The score line 68 will enable a corner of the third top panel 65 to be folded upwardly on the carton formed from the blank 10 to access the pour panel defined by the triangular second top panel 45. A third top seal panel 69 is articulated to the third top panel 65 along the fold line 67. The third top seal panel 69 is articulated to the second top seal panel 59 along fold line 60, and is further defined by fold line 70 which extends substantially colinearly from the fold line 66. A portion of the third top seal panel 69 will be securely and permanently adhered to the top seal panel 59 since it will be unnecessary to fold out the pour panel defined by the second top panel 45 as explained above and further herein.
The fourth side panel 18 is further defined by a fourth bottom fold line 71 and a fourth top fold line 72. A fourth bottom panel 73 of substantially isosceles triangular configuration is articulated to the fourth side panel 18 along the fourth bottom fold line 71. The fourth bottom panel 73 is further defined by fold lines 74 and 76 which converge toward one another from opposite ends of the fourth bottom fold line 71. Triangular web panels 78 and 80 are articulated to the fourth bottom panel 73 along fold lines 74 and 76 respectively. The triangular web panel 78 is further articulated to the third bottom panel 63 along fold line 64. The triangular web panel 80 is further defined by fold line 84.
A fourth top panel 85 is articulated to the fourth side panel 18 along the fourth top fold line 72. The fourth top panel 85 is of isosceles triangular configuration, and is defined by fold lines 86 and 87 which converge toward one another from opposite ends of the fourth top fold line 72. Triangular web panels 89 and 90 are articulated to the fourth top panel 85 along fold lines 86 and 87 respectively. The triangular web panel 89 is further articulated to the third top panel 65 along fold line 66, and is further defined by fold line 92 which extends colinearly from the fold line 67. The triangular web panel 90 is further defined b fold line 94 which extends colinearly from the fold line 92, and by fold line 96 which extends colinearly from the fold line 19. A fourth top seal panel 99 is articulated to the triangular web panels 89 and 90 along the collinear fold lines 92 and 94. The fourth top seal panel 99 is articulated to the third top seal panel 69 along fold line 70, and is further defined by fold line 100 which extends substantially colinearly from the fold line 96. The fourth top seal panel 99 will be securely adhered to portions of the third top seal panel 69 and the first top seal panel 29 on the carton erected from the blank 10.
The side seal panel 20 is further defined by bottom and top fold lines 101 and 102 which are parallel to one another and approximately aligned with the fourth bottom and top fold lines 71 and 72 respectively. A lower side seal panel 103 is articulated to the side seal panel 20 along the fold line 101 and is further articulated to the triangular web panel 80 along the fold line 84. An upper side seal panel 105 is articulated to the side seal panel 20 along fold line 102, and is further articulated to the triangular web panel 90 along fold line 96. The upper side seal panel 105 is further defined by fold line 106 which is approximately collinear with the fold line 94. A corner seal panel 109 is articulated to the upper side seal panel 105 along fold line 106 and is articulated to the fourth top seal panel 99 along fold line 100.
The assembly of components for forming the container of the subject invention further includes a closure assembly 110 which is illustrated in FIGS. 2-4 respectively. The closure assembly 110 comprises a base 112 and a cap 114. The base 112 is unitarily molded from a plastic material and includes generally planar mounting flange 116 with a circular aperture 118 extending therethrough. A substantially cylindrical pouring spout 120 extends uniformly upwardly from the mounting flange 116 and is concentric with the circular aperture 118. The outer circumferential surface of the pouring spout 120 is defined by an external array of threads 122.
The cap 114 includes a generally cylindrical engagement portion 124 having an array of internal threads 126 for threaded engagement with the threads 122 on the pouring spout 112. The cap 114 further includes a generally planar top portion 128 extending uniformly across the cylindrical engagement portion 124 and defining the portion of the cap 114 that will close the pouring spout 120. The cap 114 is further characterized by a sealing member 130 on the interior surface defined by the top 128. The sealing member 130 may be a paperboard material, a foil or a plastic material that will sealingly but releasably engage the portion of the cylindrical pouring spout 120 remote from the mounting flange 116.
The blank 10 and the closure assembly 110 are formed into the container 132 which is depicted in FIGS. 5-7. A preferred first step for manufacturing the container 132 is to form the blank 10 into a tubular structure in substantially the conventional manner. In particular, the first through fourth side wall panels 12, 14, 16 and 18 are consecutively articulated about the fold lines 13, 15 and 17 to defined a generally tubular structure. The side seal panel 20, the lower side seal panel 103, the upper side seal panel 105 and the corner seal panel 109 are then securely adhered to the portions of the blank 10 adjacent the edge 11.
As a next step, the closure assembly 110 is attached to the partly formed blank 10. In particular, the mounting flange 116 of the base 112 is attached to the second top panel 45 such that the aperture 118 therein surrounds the cutout defined by the perforations 48 in the second top panel 45. The attachment may be carried out by application of adhesive, ultrasonic welding or heat sealing. This step may be carried out such that the flange 116 is disposed exteriorly on the carton 132 as depicted in FIGS. 5-7 or, alternatively, interiorly with the pouring spout 120 extending through the cutout defined by the perforations 48.
The tubular structure described above typically is formed into a container at the facility where the container is to be filled. As part of these final steps, the bottom of the container is closed by rotating the second and fourth triangular bottom panels 33 and 73 inwardly about fold lines 31 and 71 respectively. The first and third rectangular bottom panels 23 and 63 then similarly are rotated inwardly about the fold lines 21 and 61 respectively. These inwardly folded and overlapped bottom panels are securely adhered in overlapping relationship to define a sealed bottom for the container 132.
At this point in the construction, the top portion of the container 132 is still open and can be filled with an appropriate flowable material to be stored in the container 132. After filling the second and fourth triangular top panels 45 and 85 are rotated inwardly about the fold lines 32 and 72 respectively. The rectangular first and third top panels 25 and 65 are then rotated inwardly toward one another about the fold lines 22 and 62 respectively. In this condition, the top seal panels 29, 59, 69 and 99 are securely adhered or heat sealed to one another. This top closure is substantially free of the abhesives that had been employed in the prior art.
As depicted most clearly in FIG. 5, the second top panel 45 will define a pour panel that is disposed directly beneath the triangular web panels 49 and 50 and beneath the adjacent portions of the first and third top panels 25 and 65 which define the rectangular roof panels for the gable top container 132. Additionally, as shown most clearly in FIG. 5, the triangular web panels 49 and 50 and adjacent portions of the rectangular roof panels 25 and 65 securely cover portions of the closure assembly 110 to prevent the threaded removal of the cap 114 from the base 112. In particular, the cap 114 is not readily accessible in the sealed condition of the container 132 depicted in FIG. 5. Furthermore, even if portions of the cap 114 could be accessed in the FIG. 5 condition, threaded removal is positively prevented by the adjacent web panels 49 and 50.
With reference to FIG. 6, the container 132 is initially opened by first rotating the triangular web panels 49 and 50 about the fold lines 46 and 47 respectively and simultaneously thereby folding the adjacent corners of the first and third top panels 25 and 65 about the diagonal fold lines 28 and 68 respectively. This causes a separation of portions of the second top seal panel 59 that had been secured in folded relationship to itself. This initial separation can be carried out easily and provides convenient access to the cap 114 of the closure assembly 110.
The container 132 may then be used by threadedly separating the cap 114 from the base 112 and enabling the material stored in the container 132 to be poured from the pouring spout 120. The cap may be threadedly repositioned on the spout 120 between periodic uses of the container 132.
In summary, a gable top container is provided with a paperboard carton structure having a gable top and having a threaded closure assembly securely affixed to one of the triangular pour panels. In the initial unopened condition of the carton, the cap assembly is securely retained beneath the rectangular roof panels to prevent tampering, provide evidence of tampering attempts and to prevent accidental opening of the container. The container may be employed by folding back corner regions of the rectangular roof panels to access the plastic closure assembly. The container is further employed by threadedly removing the cap of the closure assembly to enable material stored in the container to be poured from the spout.
While the invention has been defined with respect to a preferred embodiment, it is apparent that various changes can be made without departing from the scope of the invention as defined by the appended claims. For example, gable top cartons with cross sectional configurations other than the generally square shape shown herein may be employed. Furthermore, cartons with non-rectangular bottoms may be employed. The pouring spout assembly may further take other configurations, such as configurations where the mounting flange of the base is disposed interiorly on the carton and/or where the cap is engaged to interiorly disposed threads on the spout. These and other variations will be apparent to the person skilled in this art after having read the subject disclosure. | A gable top container is provided with a bottom wall, an upstanding side wall enclosure connected to and extending from the bottom wall, and a gable top. The gable top is defined by an opposed pair of triangular top panels hingedly connected to opposed portions of the side wall enclosure, and a pair of opposed rectangular top panels hingedly connected to the side walls and folded over the triangular top panels. The triangular top panels and the rectangular top panels are connected to one another by triangular top web panels. One of the triangular top panels is provided with a pouring aperture formed therethrough or with an array of perforations for defining a pouring aperture. A resealable closure assembly is affixed to the triangular top panel having the pouring aperture therein. The resealable closure assembly includes a base securely affixed to the triangular top panel. The base includes an aperture in register with the aperture in one of the triangular top panels. The resealable closure assembly futher includes a cap threadedly engageable with the base to close the container but to permit selective opening thereof. The cap is initially from opening by the web panels adjacent thereto and portions of the rectangular top panels. | 1 |
FIELD OF THE INVENTION
[0001] The invention generally relates to compositions, articles and methods for scavenging by-products of an oxygen scavenging reaction.
BACKGROUND OF THE INVENTION
[0002] It is well known that limiting the exposure of an oxygen-sensitive product to oxygen maintains and enhances the quality and “shelf-life” of the product. In the food packaging industry, several means for regulating oxygen exposure have already been developed.
[0003] These means include modified atmosphere packaging (MAP) for modifying the interior environment of a package; gas flushing; vacuum packaging; vacuum packaging combined with the use of oxygen barrier packaging materials; etc. Oxygen barrier films and laminates reduce or retard oxygen permeation from the outside environment into the package interior.
[0004] Another method currently being used is through “active packaging.” The inclusion of oxygen scavengers within the cavity or interior of the package is one form of active packaging. Typically, such oxygen scavengers are in the form of sachets which contain a composition which scavenges the oxygen through chemical reactions. One type of sachet contains iron compositions which oxidize. Another type of sachet contains unsaturated fatty acid salts on a particulate adsorbent. Yet another type of sachet contains metal/polyamide complex.
[0005] One disadvantage of sachets is the need for additional packaging operations to add the sachet to each package. A further disadvantage arising from the use of some sachets is that certain atmospheric conditions (e.g., high humidity, low CO 2 level) in the package are required in order for scavenging to occur at an adequate rate.
[0006] Another means for limiting the exposure to oxygen involves incorporating an oxygen scavenger into the packaging structure itself. This achieves a more uniform scavenging effect throughout the package. This may be specially important where there is restricted air circulation inside the package. In addition, such incorporation can provide a means of intercepting and scavenging oxygen as it passes through the walls of the package (herein referred to as an “active oxygen barrier”), thereby maintaining the lowest possible oxygen level throughout the package.
[0007] One attempt to prepare an oxygen-scavenging wall involves the incorporation of inorganic powders and/or salts. However, incorporation of these powders and/or salts causes degradation of the wall's transparency and mechanical properties such as tear strength. In addition, these compounds can lead to processing difficulties, especially in the fabrication of thin films, or thin layers within a film structure. Even further, the scavenging rates for walls containing these compounds are unsuitable for some commercial oxygen-scavenging applications, e.g. Such as those in which sachets are employed.
[0008] Other efforts have been directed to incorporating a metal catalyst-polyamide oxygen scavenging system into the package wall. However, this system does not exhibit oxygen scavenging at a commercially feasible rate.
[0009] Oxygen scavengers suitable for commercial use in films of the present invention are disclosed in U.S. Pat. No. 5,350,622, and a method of initiating oxygen scavenging generally is disclosed in U.S. Pat. No 5,211,875. Both applications are incorporated herein by reference in their entirety. According to U.S. Pat. No. 5,350,622, oxygen scavengers are made of an ethylenically unsaturated hydrocarbon and transition metal catalyst. The preferred ethylenically unsaturated hydro-carbon may be either substituted or unsubstituted. As defined herein, an unsubstituted ethylenically unsaturated hydrocarbon is any compound which possesses at least one aliphatic carbon-carbon double bond and comprises 100% by weight carbon and hydrogen. A substituted ethylenically unsaturated hydrocarbon is defined herein as an ethylenically unsaturated hydrocarbon which possesses at least one aliphatic carbon-carbon double bond and comprises about 50%-99% by weight carbon and hydrogen. Preferable substituted or unsubstituted ethylenically unsaturated hydrocarbons are those having two or more ethylenically unsaturated groups per molecule. More preferably, it is a polymeric compound having three or more ethylenically unsaturated groups and a molecular weight equal to or greater than 1,000 weight average molecular weight.
[0010] Preferred examples of unsubstituted ethylenically unsaturated hydrocarbons include, but are not limited to, diene polymers such as polyisoprene, (e.g., trans-polyisoprene) and copolymers thereof, cis and trans 1,4-polybutadiene, 1,2-polybutadienes, (which are defined as those polybutadienes possessing greater than or equal to 50% 1,2 microstructure), and copolymers thereof, such as styrene-butadiene copolymer. Such hydrocarbons also include polymeric compounds such as polypentenamer, polyoctenamer, and other polymers prepared by cyclic olefin metathesis; diene oligomers such as squalene; and polymers or copolymers with unsaturation derived from dicyclopentadiene, norbornadiene, 5-ethylidene-2-norbornene, 5-vinyl-2-norbornene, 4-vinylcyclohexene, or other monomers containing more than one carbon-carbon double bond (conjugated or non-conjugated).
[0011] Preferred substituted ethylenically unsaturated hydrocarbons include, but are not limited to, those with oxygen-containing moieties, such as esters, carboxylic acids, aldehydes, ethers, ketones, alcohols, peroxides, and/or hydroperoxides. Specific examples of such hydro-carbons include, but are not limited to, condensation polymers such as polyesters derived from monomers containing carbon-carbon double bonds, and unsaturated fatty acids such as oleic, ricinoleic, dehydrated ricinoleic, and linoleic acids and derivatives thereof, e.g. esters. Such hydrocarbons also include polymers or copolymers derived from (meth)allyl (meth)acrylates. Suitable oxygen scavenging polymers can be made by trans-esterification. Such polymers are disclosed in WO 95/02616, incorporated herein by reference as if set forth in full. The composition used may also comprise a mixture of two or more of the substituted or unsubstituted ethylenically unsaturated hydrocarbons described above. While a weight average molecular weight of 1,000 or more is preferred, an ethylenically unsaturated hydrocarbon having a lower molecular weight is usable, provided it is blended with a film-forming polymer or blend of polymers.
[0012] As will also be evident, ethylenically unsaturated hydrocarbons which are appropriate for forming solid transparent layers at room temperature are preferred for scavenging oxygen in the packaging articles described above. For most applications where transparency is necessary, a layer which allows at least 50% transmission of visible light is preferred.
[0013] When making transparent oxygen-scavenging layers according to this invention, 1,2-polybutadiene is especially preferred for use at room temperature. For instance, 1,2-polybutadiene can exhibit transparency, mechanical properties and processing characteristics similar to those of polyethylene. In addition, this polymer is found to retain its transparency and mechanical integrity even after most or all of its oxygen capacity has been consumed, and even when little or no diluent resin is present. Even further, 1,2-polybutadiene exhibits a relatively high oxygen capacity and, once it has begun to scavenge, it exhibits a relatively high scavenging rate as well.
[0014] When oxygen scavenging at low temperatures is desired, 1,4-polybutadiene, and copolymers of styrene with butadiene, and styrene with isoprene are especially preferred. Such compositions are disclosed in U.S. Pat. No. 5,310,497 issued to Speer et al. on May 10, 1994 and incorporated herein by reference as if set forth in full. In many cases it may be desirable to blend the aforementioned polymers with a polymer or copolymer of ethylene.
[0015] Other oxygen scavengers which can be used in connection with this invention are disclosed in U.S. Pat. Nos. 5,075,362 (Hofeldt et al.), 5,106,886 (Hofeldt et al.), 5,204,389 (Hofeldt et al.), and 5,227,411 (Hofeldt et al.), all incorporated by reference herein in their entirety. These oxygen scavengers include ascorbates or isoascorbates or mixtures thereof with each other or with a sulfite, often sodium sulfite.
[0016] Still other oxygen scavengers which can be used in connection with this invention are disclosed in PCT patent publications WO 91/17044 (Zapata Industries) and WO94/09084 (Aquanautics Corporation), both incorporated by reference herein in their entirety. These oxygen scavengers include an ascorbate with a transition metal catalyst, the catalyst being a simple metal or salt or a compound, complex or chelate of the transition metal; or a transition metal complex or chelate of a polycarboxylic or salicylic acid or polyamine, optionally with a reducing agent such as ascorbate, where the transition metal complex or chelate acts primarily as an oxygen scavenging composition.
[0017] Yet other oxygen scavengers which can be used in connection with this invention are disclosed in PCT patent publication WO 94/12590 (Commonwealth Scientific and Industrial Research Organisation), incorporated by reference herein in its entirety. These oxygen scavengers include at least one reducible organic compound which is reduced under predetermined conditions, the reduced form of the compound being oxidizable by molecular oxygen, wherein the reduction and/or subsequent oxidation of the organic compound occurs independent of the presence of a transition metal catalyst. The reducible organic compound is preferably a quinone, a photoreducible dye, or a carbonyl compound which has absorbence in the UV spectrum.
[0018] Sulfites, alkali metal salts of sulphites, and tannins, are also contemplated as oxygen scavenging compounds.
[0019] As indicated above, the ethylenically unsaturated hydrocarbon is combined with a transition metal catalyst. While not being bound by any particular theory, the inventors observe that suitable metal catalysts are those which can readily interconvert between at least two oxidation states. See Sheldon, R. A.; Kochi, J. K.; “ Metal-Catalyzed Oxidations of Organic Compounds” Academic Press, New York 1981.
[0020] Preferably, the catalyst is in the form of a transition metal salt, with the metal selected from the first, second or third transition series of the Periodic Table. Suitable metals include, but are not limited to, manganese II or III, iron II or III, cobalt II or III, nickel II or III, copper I or II, rhodium II, III or IV, and ruthenium II or III. The oxidation state of the metal when introduced is not necessarily that of the active form. The metal is preferably iron, nickel or copper, more preferably manganese and most preferably cobalt. Suitable counterions for the metal include, but are not limited to, chloride, acetate, stearate, palmitate, caprylate, linoleate, tallate, 2-ethylhexanoate, neodecanoate, oleate or naphthenate. Particularly preferable salts include cobalt (II) 2-ethylhexanoate and cdbalt (II) neodecanoate. The metal salt may also be an ionomer, in which case a polymeric counterion is employed. Such ionomers are well known in the art.
[0021] The ethylenically unsaturated hydrocarbon and transition metal catalyst can be further combined with one or more polymeric diluents, such as thermoplastic polymers which are typically used to form film layers in plastic packaging articles. In the manufacture of certain packaging articles well known thermosets can also be used as the polymeric diluent.
[0022] Polymers which can be used as the diluent include, but are not limited to, polyethylene terephthalate (PET), polyethylene, low or very low density polyethylene, ultra-low density polyethylene, linear low, density polyethylene, polypropylene, polyvinyl chloride, polystyrene, and ethylene copolymers such as ethylene-vinyl acetate, ethylene-alkyl (meth) acrylate s, ethylene-(meth)acrylic acid and ethylene-(meth) acrylic acid ionomers. Blends of different diluents may also be used. However, as indicated above, the selection of the polymeric diluent largely depends on the article to be manufactured and the end use. Such selection factors are well known in the art.
[0023] Further additives can also be included in the composition to impart properties desired for the particular article being manufactured. Such additives include, but are not necessarily limited to, fillers, pigments, dyestuffs, antioxidants, stabilizers, processing aids, plasticizers, fire retardants, anti-fog agents, etc.
[0024] The mixing of the components listed above is preferably accomplished by melt-blending at a temperature in the range of 50° C. to 300° C. However alternatives such as the use of a solvent followed by evaporation may also be employed. The blending may immediately precede the formation of the finished article or preform or precede the formation of a feedstock or masterbatch for later use in the production of finished packaging articles.
[0025] Although these technologies offers great potential in packaging applications, it has been found that oxygen scavenging structures can sometimes generate reaction byproducts which can affect the taste and smell of the packaged material (i.e. organoleptic properties), or raise food regulatory issues. These by-products can include acids, aldehydes and ketones.
[0026] The inventors have found that this problem can be minimized by the use of zeolites (such as organophilic zeolites) which absorb odor-causing reaction byproducts. The zeolites can be incorporated into one or more layers of a multilayer film or container which includes an oxygen scavenging layer. However, one of ordinary skill in the art will readily recognize that the present invention is applicable to any oxygen scavenging system that produces by-products such as Acids, aldehydes, and ketones.
[0027] Definitions
[0028] “Film” (F) herein means a film, laminate, sheet, web, coating, or the like which can be used to package a product.
[0029] “Zeolite” herein refers to molecular sieves, including alumino-phosphates and aluminosilicates with a framework structure enclosing cavities occupied by large ions and/or water molecules, both of which have considerable freedom of movement permitting ion exchange and reversible dehydration. The framework may also contain other cations such as Mn, Ti, Co, and Fe. An example of such materials are the titanosilicate and titanoaluminosilicate molecular sieves. Unlike amor-phous materials, these crystalline structures contain voids of discrete size. A typical naturally occurring zeolite is the mineral faujasite with formula
[0030] Na 13 Ca 11 Mg 9 K 2 Al 55 Si 137 O 384 .235H 2 O.
[0031] Ammonium and alkylammonium cations may be incorporated in synthetic zeolites, e.g. NH 4 , CH 3 NH 3 , (CH 3 ) 2 NH 2 , (CH 3 ) 3 NH, and (CH 3 ) 4 N. Some zeolites have frameworks of linked truncated octahedra (Beta-cages) characteristic of the structure of sodalite. Numerous synthetic zeolites are available.
[0032] “Oxygen scavenger” (OS) and the like herein means a composition, article or the like which consumes, depletes or reacts with oxygen from a given environment.
[0033] “Actinic radiation” and the like herein means any form of radiation, such as ultraviolet radiation or electron beam irradiation, disclosed in U.S. Pat. No. 5.211,875 (Speer et al.).
[0034] “Polymer” and the like herein means a homopolymer, but also copolymers thereof, including bispolymers, terpolymers, etc.
[0035] “Ethylene alpha-olefin copolymer” and the like herein means such heterogeneous materials as linear low density polyethylene (LLDPE), linear medium density polyethylene (LMDPE) and very low and ultra low density polyethylene (VLDPE and ULDPE); and homogeneous polymers such as metallocene catalyzed polymers such as EXACT (TM) materials supplied by Exxon, and TAFMER (TM), materials supplied by Mitsui Petrochemical Corporation. These materials generally include copolymers of ethylene with one or more comonomers selected from C 4 to C 10 alpha-olefins such as butene-1 (i.e., 1-butene), hexene-1, octene-1, etc. in which the molecules of the copolymers comprise long chains with relatively few side chain branches or cross-linked structures. This molecular structure is to be contrasted with conventional low or medium density polyethylenes which are more highly branched than their respective counterparts. Other ethylene/alpha-olefin copolymers, such as the long chain branched homogeneous ethylene/alpha-olefin copolymers available from the Dow Chemical Company, known as AFFINITY. (TM) resins, are also included as another type of ethylene alpha-olefin copolymer useful in the present invention.
[0036] As used herein, the term “polyamide” refers to polymers having amide linkages along the molecular chain, and preferably to synthetic polyamides such as nylons. Furthermore, such term encompasses both polymers comprising repeating units derived from monomers, such as caprolactam, which polymerize to form a polyamide, as well as copolymers of two or more amide monomers, including nylon terpolymers, also referred to generally as “copolyamides” herein.
[0037] “LLDPE” herein means linear low density polyethylene, which is an ethylene alpha olefin copolymer.
[0038] “EVOH” herein means ethylene vinyl alcohol copolymer.
[0039] “EVA” herein means ethylene vinyl acetate copolymer.
SUMMARY OF THE INVENTION
[0040] In one aspect of the invention, an article of manufacture comprises an oxygen scavenger and a zeolite.
[0041] In a second aspect of the invention, a package comprisesan article and a container into which the oxygen sensitive article is disposed, the container including a component comprising an oxygen scavenger and a zeolite.
[0042] In a third aspect of the invention, a method of making an article of manufacture having reduced migration of by-products of an oxygen scavenging reaction comprises providing an article comprising an oxygen scavenger and a zeolite and exposing the article to actinic radiation.
BRIEF DESCRIPTION OF THE DRAWINGS
[0043] The invention may be further understood with reference to the drawings wherein FIGS. 1 through 5 are schematic cross-sections of various embodiments of a film of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0044] The invention can be used to make various articles of manufacture, compounds, compositions of matter, coatings, etc. Two preferred forms are sealing compounds, and flexible films, both useful in packaging of food and non-food products.
[0045] It is known to use sealing compounds in the manufacture of gaskets for the rigid container market. Large, wide diameter gaskets are typically made using a liquid plastisol. This plastisol is a highly viscous, liquid suspension of polymer particles in a plasticizer. In the manufacture of metal or plastic caps, lids, and the like, this liquid plastisol is applied to the annulus of a container such as a jat, and the container with the applied plastisol is “fluxed” in an oven to solidify the plastisol into a gasket. The result is a gasket formed around the annulus of the container.
[0046] Smaller gaskets are typically made for use in beer crowns in bottles. A polymer melt is applied by cold molding to the entire inner surface of the crown. Both PVC and other polymers are used in this application.
[0047] Discs for plastic caps are typically made by taking a ribbon of gasket material and making discs, and inserting the discs into the plastic cap.
[0048] In all of these applications, the use of an oxygen scavenger and zeolite beneficially provides removal of oxygen from the interior environment of the container, while controlling undesirable by-products of the oxygen scavenging reaction.
[0049] Thus, a gasket includes a polymeric composition, an oxygen scavenger, and a zeolite. The gasket adheres a metal or plastic lid or closure to a rigid or semi-rigid container, thus sealing the lid or closure to the container.
[0050] Referring to FIG. 1, a multilayer film 10 is shown, having layer 12 and layer 14 .
[0051] [0051]FIG. 2 shows a multilayer film with layers 12 , 14 , and 16 . Layers 12 , 14 , and 16 are preferably polymeric.
[0052] Layer 12 comprises a zeolite. Preferred materials are the molecular sieves of the type disclosed in U.S. Pat. No. 4,795,482 (Gioffre et al.), incorporated herein by reference in its entirety. Also useful in the present invention are zeolites supplied by the Davison division of W.R.Grace &, Co.-Conn. Preferred particle sizes for zeolites used in the present invention are between 0.1 and 10 micrometers, and more preferably between 0.5 and 3 micrometers.
[0053] Layer 14 comprises an oxygen scavenger, preferably a polymeric oxygen scavenger, more preferably one of the materials described above.
[0054] Layer 16 comprises an oxygen barrier material, such as ethylene vinyl alcohol copolymer (EVOH), Saran (vinylidene chloride copolymer), polyester, polyamide, metal, silica coating, etc.
[0055] [0055]FIG. 3 shows a laminated film in which a three layer film is adhered to a second film. Layers 32 , 34 , and 36 correspond functionally and compositionally to 12 , 14 , and 16 respectively of FIG. 2, and layer 38 is an intermediate layer which can comprise any polymeric material such as polyolefin, more preferably ethylenic polymers such as ethylene/alpha-olefin and ethylene/unsaturated ester copolymers, more preferably ethylene/vinyl acetate copolymer. Layer 31 represents a conventional adhesive such as polyurethane adhesive. Comparative 2 in Table 6 exemplifies the laminated film of FIG. 3.
[0056] [0056]FIG. 4 shows a laminated film in which a four layer film is adhered to a second film. Layers 42 , 44 , 46 and 48 correspond functionally and compositionally to layers 32 , 34 , 36 and 38 respectively of FIG. 3. Layer 49 is an innermost heat sealable layer which can comprise any polymeric material such as polyolefin, more preferably ethylenic polymers such as ethylene/alpha-olefin and ethyene/unsaturated ester copolymers, such as ethylene vinyl acetate copolymer. Layer 46 provides oxygen barrier to the film structure, and adheres to layer 48 by means of conventional adhesive 41 . This adhesive corresponds to layer 31 of FIG. 3, and is shown simply as a thickened line. Examples 2 and 3 of Table 6 exemplify the laminated film of FIG. 4.
[0057] [0057]FIG. 5 shows a nine layer film. Example 1 and Comparative 1 in Table 2 exemplify the film of FIG. 5.
[0058] Layer 57 is an abuse-resistant layer useful as an outermost layer of a film when used in a packaging application.
[0059] Layers 54 and 56 correspond functionally and compositionally to layers 14 and 16 respectively of FIGS. 2 and 3, as well as to layers 44 and 46 respectively of FIG. 4.
[0060] Layers 52 , 53 , 58 and 59 comprise an adhesive. The adhesive is preferably polymeric, more preferably acid or acid anhydride-grafted polyolefins. In addition, these layers can comprise a zeolite.
[0061] Layer 55 comprises a heat resistant material. This can be any suitable polymeric material, preferably an amide polymer such as nylon 6 , or a polyester such as polyethylene terephthalate.
[0062] Layer 51 comprises a heat sealable material. This can be any suitable polymeric material, preferably an olefinic polymer such as an ethylenic polymer, more preferably an ethylene alpha olefin copolymer. In addition, layer 51 can further comprise a zeolite.
[0063] The invention may be further understood by reference to the examples shown below. Table 1 identifies the materials used in the examples. The remaining tables describe the films made with these materials, and organoleptic or migration data resulting from testing some of these films.
TABLE 1 MATERIAL TRADENAME SOURCE DESCRIPTION PE 1 Dowlex ™ 3010 Dow LLDPE, an ethylene/ 1- octene copolymer with a density of 0.921 gm/cc PE 2 Dowlex ™ 2244 A Dow LLDPE, an ethylene/ 1- octene copolymer with a density of 0.916 gm/cc PE 3 Poly-eth 1017 Chevron low density polyethylene PE 4 AC-9A Allied polyethylene powder AB 1 10,075 ACP Sy- Tecknor 89.8% low density loid ™ antiblock Color polyethylene (Exxon LD concentrate 203.48) + 10% synthetic amorphous silica (Syloid ™ 74X6500 from Davison Chemical) + 0.2% calcium stearate PP 1 Escorene Exxon polypropylene PP292.E1 Z 1 10414-12 zeolite Colortech masterbatch of 80% concentrate LLDPE and 20% UOP Abscents ® 3000 zeolite Z 2 10417-12 zeolite Colortech masterbatch of 80% concentrate LLDPE and 20% UOP Abscents ® 2000 zeolite Z 3 USY zeolite Grace zeolite Davison Z 4 ZSM-5 zeolite Grace zeolite Davison Z 5 ZN-1 Grace zeolite Davison Z 6 X5297H Engelhard titanium silicate zeolite AD 1 Plexar ™ 107 Quantum anhydride-grafted EVA AD 2 Adcote 530 and Morton mixture of silane, isocy- Coreactant 9L23 Inter- anate, glycol, and alkyl national acetate PA 1 Ultramid ™ KR BASF nylon 6 4407-F (polycaprolactam) OB 1 LC-H101BD Evalca ethylene/vinyl alcohol copolymer with 38 mole % ethylene OS 1 RB-830 JSR 1,2-polybutadiene OS 2 VISTALON ™ Exxon ethylene-propylene-diene 3708 terpolymer OS 3 VECT0R ™ 8508- Dexco styrene/butadiene copoly- D mer with 30% by weight of the styrene comonomer, and 70% by weight of the butadiene comonomer EV 1 MU-763 Quantum ethylene/vinyl acetate copolymer EV 2 PE 1375 Rexene ethylene/vinyl acetate copolymer with 3.6 wt. % vinyl acetate comonomer EV 3 LD-318.92 Exxon ethylene/vinyl acetate co- polymer with 9 wt. % vinyl acetate comonomer EB 1 Lotryl 30BA02 Atochem ethylene/butyl acrylate copolymer with 30 wt. % butyl acrylate copolymer PI 1 benzophenone Sartomer photoinitiator PI 2 benzoylbiphenyl — photoinitiator TC 1 TENCEM ™ 170 OMG cobalt neodecanoate, a transition metal catalyst TC 2 cobalt oleate Shepherd a transition metal catalyst F 1 50m-44 Mylar ™ Dupont Saran-coated polyethylene terephthalate film
[0064] Certain materials were blended together for some of the film structures, and these blends are identified as follows:
PEB 1 =90% PE 1 +10% AB 1 .
PEB 2 =90% PE 1 +10% PEB 3 .
PEB 3 =80% PE 3 +20% PE 4 .
PPB 1 =60% PP 1 +40% EB 1 .
PPB 2 =40% PP 1 +60% EB 1 .
OSB 1 =76.5% OS 1 +13.5% OS 2 +9.2% EV 1 +0.5% Pl 1 +0.3% TC 1 .
OSB 2 =50% OS 3 +40% PE 3 +8.54% EV 1 +0.90% TC 1 +0.50% PI 1 +0.05% calcium oxide+0.01% antioxidant (Irganox 1076).
OSB 3 =60% OS 3 +38.83% EV 3 +1.06% TC 2 +0.10% Pl 2 +0.01% antioxidant (Irganox 1076).
OSB 4 =40% OS 3 +58.83% EV 3 +1.06% TC 2 +0.10% Pl 2 +0.01% antioxidant (Irganox 1076).
ZB 1 =87% PE 1 +10% AB 1 +3% Z 1 .
ZB 2 =90% PE 2 +10% Z 1 .
ZB 3 =90% PE 2 +10% Z 2 .
ZB 4 =90% PE 2 +6% PE 3 +2% PE 4 +1% Z 3 +1% Z 4
ZB 5 =80% PE 2 +20% Z 2 .
ZB 6 =80% PE 3 +20% Z 2 .
[0065] In Table 2, a nine-layer film structure in accordance with the invention, and a comparative film, are disclosed. These were each made by coextrusion of the layers.
TABLE 2 EXAMPLE STRUCTURE 1 PEB 1 /AD 4 /OB 1 /AD 4 /OSB 1 /AD 4 /PA 1 /AD 4 /ZB 2 COMP. 1 PEB 1 /AD 4 /OB 1 /AD 4 /OSB 1 /AD 4 /PA 1 /AD 4 /PEB 1
[0066] The target (and approximate actual) gauge (in mils) of each layer of the nine-layer film is shown below. Layer 9 would preferably form the food or product contact layer in a typical packaging application.
layer layer layer layer layer layer layer layer layer 1 2 3 4 5 6 7 8 9 1.35 0.20 0.50 0.20 0.50 0.20 1.00 0.20 1.35
[0067] The films of Example 1 and Comparative 1 were subjected to food law migration tests to evaluate whether zeolites could reduce the concentration of extractables. The films were triggered by ultraviolet light according to the procedure disclosed in U.S. Pat. No. 5,211,875. The films were converted into 280 cm 2 pouches and the pouches were filled with a food simulant. The filled pouches were then retorted at 100° C. for 30 minutes and stored at 50° C. for 10 days. The food simulant was decanted from the pouches and analyzed. Table 3 shows a list of potential extractables. Table 4 shows the concentration of the same extractables, where the films were extracted with 8% ethanol solution as the food simulant. Table 5 shows the concentration of the same extractables, where the films were extracted with water as the food simulant. In both Tables 4 and 5, the concentration of each extractable is in units of nanograms/milliliter. Zeolites can reduce the concentration of certain extractables which could cause regulatory issues.
TABLE 3 ABBREVIATION DESCRIPTION E 1 benzophenone E 2 triphenyl phosphine oxide E 3 Permanax ™ WSP (antioxidant)* E 4 dilauryl thiodipropionate E 5 methyl formate E 6 ethyl formate E 7 methanol E 8 formaldehyde E 9 acetaldehyde E 10 acetone E 11 acrolein (2-propenal) E 12 propanal
[0068] [0068] TABLE 4 EX. E 1 E 2 E 3 E 4 E 5 E 6 E 7 E 8 E 9 E 10 1 21 21 <10 <5 <600 <300 3,310 1,400 6,700 100 COMP. 1 <20 40 <10 <5 <600 <300 2,960 1,600 7,800 80
[0069] [0069] TABLE 5 EX. E 1 E 2 E 3 E 4 E 5 E 6 E 7 E 8 E 9 E 10 1 22 13 <10 <5 <600 <300 <600 320 780 50 COMP. 1 21 16 <10 <5 <600 <300 <600 310 730 50
[0070] In Table 6, two five-layer laminate structures in accordance with the invention, and one comparative four-layer laminate structure, are disclosed. The two five-layer structures were each made by laminating a coextruded four-layer film, using a conventional adhesive, to a second film (=layer 5 ). The comparative structure was made by laminating a coextruded three-layer film, using a conventional adhesive, to a second film (=layer 4 ).
TABLE 6 EXAMPLE STRUCTURE 2 PE 2 /ZB 2 /OSB 2 /EV 2 //AD 2 //F 1 3 PE 2 /ZB 3 /OSB 2 /EV 2 //AD 2 //F 1 COMP. 2 PE 2 /OSB 2 /EV 2 //AD 2 //F 1
[0071] The target (and approximate actual) gauge (in mils) of each layer of the laminate structures of the invention was:
layer 1 layer 2 layer 3 layer 4 adhesive layer 5 0.20 0.20 0.50 1.00 (minimal) 0.50
[0072] The target (and approximate actual) gauge (in mils) of each layer of the comparative laminate structures was:
layer 1 layer 2 layer 3 adhesive layer 4 0.40 0.51 1.04 (minimal) 0.50
[0073] The film of Examples 2 and 3 were subjected to food law migration tests to evaluate whether zeolites could remove oxidation by-products. Their efficacy was compared with Comparative 2. The list of extractables can be found in Table 3. The test results from the extraction of the films with Miglyol 812 (available from Huls America), a fatty food simulant, are summarized in Table 7. Zeolites can reduce the concentration of certain extractables which could cause regulatory issues.
TABLE 7 Migrant (ppb) COMP. 2 EX. 2 EX. 3 E 9 <Q.L. <Q.L. <Q.L. E 10 <Q.L. <Q.L. <Q.L. E 11 <D.L. <D.L. <D.L. E 1 980 1000 +/− 5 875 +/− 23 E 8 <D.L. <D.L. <D.L. E 12 <D.L. <D.L. <D.L.
[0074] D.L.=detection limit=50 parts per billion (food equivalent).
[0075] Q.L.=quantifiable limit=150 parts per billion (food equivalent).
[0076] In Table 8, three five-layer laminate structures in accordance with the invention, and one comparative five-layer laminate structure, are disclosed. The five-layer structures were each made by laminating a coextruded four-layer film, using a conventional adhesive, to a second film (=layer 5 ).
TABLE 8 EXAMPLE STRUCTURE 4 PE 2 /ZB 2 /OSB 3 /EV 2 //AD 2 //F 1 5 PE 2 /ZB 3 /OSB 3 /EV 2 //AD 2 //F 1 6 PE 2 /ZB 4 /OSB 3 /EV 2 //AD 2 //F 1 COMP. 3 PE 2 /PEB 2 /OSB 3 /EV 2 //AD 2 //F 1
[0077] The target (and approximate actual) gauge (in mils) of each layer of the laminate structures of the invention and the comparative was:
layer 1 layer 2 layer 3 layer 4 adhesive layer 5 0.15 0.15 0.50 1.00 (minimal) 0.50
[0078] Sliced turkey breast was stored in packages made from the films of Examples 4, 5, 6 and Comparative 3. A sensory panel tasted the turkey slices to evaluate whether or not zeolites can reduce the off-flavor caused by byproducts of the oxygen-scavenging reaction.
[0079] The films were triggered by ultraviolet light according to the procedure disclosed in U.S. Pat. No. 5,211,875. The films were converted into packages on a Multivac® R7000 packaging machine. Cryovac® T6070B film was used as the bottom web of the packages. Each package contained one slice of turkey. Each package was flushed with a gas mixture consisting of 99% N 2 and 1% O 2 . Packages were stored in the dark for 7 days at 40° F.
[0080] A sensory panel rated the taste of the turkey slices. The scale ranged from 1 to 6, with 1 indicating extreme off-flavor and 6 indicating no off-flavor. The average scores are summarized in Table 9. In some cases, zeolites can reduce the off-flavor caused by the byproducts of the oxygen-scavenging reaction.
TABLE 9 Film Average Score 4 2.3 5 3.9 6 2.5 COMP. 3 2.6
[0081] In Table 10, two five-layer laminate structures in accordance with the invention, and two comparative five-layer laminate structure, are disclosed. The five-layer structures were each made by laminating a coextruded four-layer film, using a conventional adhesive, to a second film (=layer 5 ).
TABLE 10 EXAMPLE STRUCTURE 7 ZB 5 /PPB 1 /OSB 4 /ZB 6 //AD 2 //F 1 COMP. 4 PE 2 /PPB 1 /OSB 4 /PE 2 //AD 2 //F 1 8 ZB 5 /PPB 2 /OSB 4 /ZB 6 //AD 2 //F 1 COMP. 5 PE 2 /PPB 2 /OSB 4 /PE 2 //AD 2 //F 1
[0082] The target (and approximate actual) gauge (in mils) of each layer-of the laminate structures of the invention and the comparative was:
layer 1 layer 2 layer 3 layer 4 adhesive layer 5 0.15 0.15 0.50 1.00 (minimal) 0.50
[0083] Sliced turkey breast was stored in packages made from the films of Examples 7 and 8 and Comparatives 4 and 5. A sensory panel tasted the turkey slices to evaluate whether or not zeolites can reduce the off-flavor caused by the byproducts of the oxygen-scavenging reaction.
[0084] The films were triggered by ultraviolet light according to the procedure disclosed in U.S. Pat. No. 5,211,875. The films were converted into packages on a Multivac® R7000 packaging machine. Cryovac® T6070B film was used as the bottom web of the packages. Each package contained one slice of turkey. Each package was flushed with a gas mixture consisting of 99% N 2 and 1% O 2 . Packages were stored in the dark for 7days at 40° F.
[0085] A sensory panel rated the taste of the turkey slices. The scale ranged from 1 to 6, with 1 indicating extreme off-flavor and 6 indicating no off-flavor. Table 11 summarizes the percentage of the panelists which did not taste an off-flavor (i.e. a score of 6) in the packaged turkey slices. In some cases, zeolites can significantly reduce the off-flavor caused by the byproducts of the oxygen-scavenging reaction.
TABLE 11 Percentage of Panelist which did not taste an off-flavor in the Film packaged turkey 7 39% COMP. 4 17% 8 17% COMP. 5 13%
[0086] A headspace gas chromatography (GC) method was used to determine the ability of a material to absorb aldehydes. The material (either 6 to 7 mg of powder or 25 mm disk of LLDPE film containing 4% absorber) was placed in a headspace GC vial (22 mL), and 2 μL of an aldehyde mixture containing about 0.1% each of the indicated aldehydes in methanol was injected into each vial. The vials were incubated at 80° C. for 1 hour and were injected into a GC. The data in Table 12 shows the percent change in the aldehyde concentration for each material relative to an appropriate control (vial with no absorber or LLDPE disk).
TABLE 12 Percent of Aldehydes Absorbed by Candidate Absorbers Sample Propenal Pentanal Hexanal Heptanal Octanal Percent Chance Relative to Aldehyde Control Z 5 −77 4 −18 −21 −28 Z 6 −57 −93 −99 −100 −100 Percent Change Relative to LLDPE Control Z 4 −95 n/t c −100 −85 n/t Z 3 −92 n/t −77 −100 n/t
[0087] The data in Table 12 shows that various zeolites are capable of reducing the migration of aldehydes. In addition, due to specificity of various materials it can be seen that blends of materials can be advantageous.
[0088] Films of the invention can been made by any conventional means, including coextrusion, lamination, extrusion coating, or corona bonding, and then optionally irradiated and/or oriented. They can be made heat shrinkable through orientation or tenterframing if desired, at orientation ratios of 1:2 to 1:9 in either or both of the machine and transverse directions. For shrink applications, they can be made to have a free shrink of at least 10%, more preferably at least 20%, most preferably at least 30%, in either or both directions at 90° C.
[0089] Gasket compositions of the invention can be made by any conventional process, including, but not limited to, extrusion compounding for thermoplastic compositions, and conventional mixing equipment for plastisol compositions. The gasket compositions of the invention can then be formed into gaskets on lids by any conventional process, including but not limited to, cold molding processes, inserted discs, application of liquid plastisols via pressurized nozzles followed by solidification in an oven, etc.
[0090] Various changes and modifications may be made without departing from the scope of the invention defined below. For example, a blend of different zeolites can be used in the same article (e.g. film or sealing compound). In films, although it is preferred that the zeolite be used in the film and as a packaging material such that the zeolite is disposed closer to the contents of the package, which can be food or any oxygen-sensitive product, than the oxygen scavenger, there may be applications where the zeolite is disposed “outside of” the oxygen scavenger, such that the oxygen scavenger-containing layer is disposed closer to the contents of a package made from the film, than the zeolite-containing layer. The zeolite can alternatively be disposed on both sides of the oxygen scavenger. Also, within the same film, a first zeolite can be used in a first layer, and a second zeolite, different from the first zeolite, can be used in another layer of the film.
[0091] Alternatively, the zeolite, in addition to or instead of the arrangements described above, can be disposed in the same layer or layers as the oxygen scavenging material. Thus, by way of example, any of layers 14 , 34 , 44 , and 54 of the examples and figures can include any suitable percent, by weight of the layer, of a zeolite. A preferred blend of oxygen scavenging and zeolite in such a blend layer is between 95% and 99.5% oxygen scavenger, and between 0.5% and 5% zeolite. Any suitable polymeric materials can be employed in films containing the zeolites, and are not limited to those listed herein.
[0092] The amount of zeolite used in a film of the present invention is preferably between 0.1% and 5% of the layer in which it occurs; These percentages are based on the zeolite material (e.g. zeolite) per se, with suitable adjustment to be made if the zeolite material is used as a masterbatch with another material such as polyethylene. Above 5% of the layer, optics of the film can be compromised to some extent, although the film can still be used in many applications. In end-use applications where optics are not a critical feature of the package, such as opaque films or gaskets for containers, higher amounts of zeolites can be beneficially used.
[0093] Zeolites disclosed herein can be used with or in films or coatings, or absorbed into a variety of other supports for scavenging or other uses, such as a layer or coating on another object, or as a bottle cap or bottle liner, as an adhesive or non-adhesive insert, sealant, gasket, fibrous matte or other inserts, or as a non-integral component of a rigid, semi-rigid, or flexible container. | An article of manufacure includes an oxygen scavenger and a zeolite. The article can be in the form of e.g. a film or sealing compound. A package can be made from the article for containing an oxygen-sensitive article such as food. The zeolite reduces migration of odor causing by-products of the oxygen scavenging process. A method of making an article of manufacture having reduced migration of by-products of an oxygen scavenging reaction includes providing an article including an oxygen scavenger and a zeolite; and exposing the article to actinic radiation. | 1 |
RELATED APPLICATION DATA
This application claims a priority filing date under 35 U.S.C. §119(e) from U.S. Provisional Application No. 60/991,320, filed Nov. 30, 2007, the disclosure of which is hereby expressly incorporated herein by reference.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This application relates to polysiloxane compositions grafted with improved heat curable, moisture curable, or heat/moisture curable groups. In particular, the polysiloxane compositions have reactive groups on the terminal or pendent areas of the siloxane backbone, which once reacted provide improved heat and/or moisture curable polysiloxanes.
2. Brief Description of the Related Technology
Moisture-curing mechanisms, heat-curing mechanisms, and light-curing mechanisms are among the means used to initiate cure, i.e., cross-linking, of reactive compositions, such as reactive silicones. These mechanisms are based on either condensation reactions, whereby moisture hydrolyzes certain groups, or addition reactions that can be initiated by a form of energy, such as electromagnetic radiation or heat. In certain compositions, a combination of such cure mechanisms may be used to achieve the desired results.
For example, reactive polyorganosiloxanes can be cured in the presence or absence of heat in the presence of a peroxide. Alternatively, these reactive siloxanes can also be cured in the presence or absence of heat in the presence of silicone hydride-containing (—SiH) compounds and a metallic hydrosilylation catalyst, such as an organo-platinum catalyst.
Dual curing silicone compositions are also known. However, generally, these dual-curing compositions have been limited to compositions that are both light-curing and moisture-curing. See U.S. Pat. Nos. 4,528,081 (Nakos) and U.S. Pat. Nos. 4,699,802 (Nakos), the disclosures of each of which are hereby incorporated herein by reference.
Notwithstanding the state of the technology, it would be desirable to provide a curable composition, where the composition would be curable in the presence of heat and/or moisture, as well as heat and/or light, or moisture and/or light, which demonstrates commercially acceptable tack free time upon curing.
SUMMARY OF THE INVENTION
In one aspect of the invention, there is provided a curable composition having at least one component, which has the structure:
R 1 -A-R 2
In this aspect of the invention, A is a hydrocarbon or heterohydrocarbon backbone having at least one pendent vinyl group or a siloxane backbone having at least one vinyl, alkoxy or hydride pendent group. R 1 and R 2 may be the same or different and are each independently either a vinyl-containing group, an alkoxy-containing group, an alkyl-containing group, a (meth)acryloxy-containing group or a hydride-containing group, provided that (i) when A is a hydrocarbon or heterocarbon backbone, having at least one pendent vinyl group, R 1 and R 2 are alkyl groups; (ii) when A is a siloxane backbone, having at least one pendent vinyl group, R 1 and R 2 are either vinyl, alkoxyl or alkyl groups; and (iii) when A is a siloxane backbone, having at least one pendent hydride group, R 1 and R 2 are either a hydride-containing, alkyl-containing, alkoxy-containing, or (meth)acryloxy-containing groups.
In another aspect of the invention, there is provided a curable composition having at least one component, which has the structure:
In this aspect, R in each occurrence may be the same or may be different and is has 1 to 4 carbons. R 1 is a substituted or unsubstituted alkylenylsiloxy group, a substituted or unsubstituted alkylenyl(meth)acryloxy group, a substituted or unsubstituted alkylenylenoxy group, a substituted or unsubstituted alkylenyloximino group, or a substituted or unsubstituted alkylenylacetoxy group. R 2 is a (meth)acryloxy group. R 3 is an unsaturated group. R 4 and R 5 may be the same or may be different and may independently be any of the groups of R, R 1 , R 2 or R 3 . n is any integer from 1 to 12,000, m is any integer from about 1 to about 20, and p is any integer from about 0 to about 20.
In another aspect of the invention, there is provided a curable composition having a first component, which has a siloxane polymeric backbone having at least one vinyl group terminating at the end and at least two pendent groups off the polymeric backbone. At least one of the pendent groups is a moisture-curing group, and at least one of the pendent groups has the structure:
In this aspect of the invention, R 1 , R 2 and R 3 may be the same or may be different, and may independently be a vinyl containing group, an alkoxy-containing group, an alkyl-containing group, an acryloxy-containing group or a hydride-containing group.
In a further aspect of the invention, there is provided a method of preparing a curable composition, which includes the steps of reacting a first component, which has the structure:
with a second component, which has the structure:
to form a curable composition, which has the structure:
In this aspect of the invention, R, R 2 , and R 3 may be the same or may be different, and may independently be a vinyl containing group, an alkoxy-containing group, an alkyl-containing group, an acryloxy-containing group and a hydride-containing group. R 1 is a hydride-containing group. n is an integer from 1 to about 20.
In yet another aspect of the invention there is provided a method of preparing a curable composition, which includes the steps of reacting a first component having the structure:
with a second component having the structure:
to form a curable composition having the structure:
In this aspect of the invention, R and R 1 may be the same or may be different, and may independently be an alkyl-substituted silane group, an alkyl-containing group, or an alkoxy-containing group. R 2 , R 3 , and R 4 may be the same or may be different, and may independently be a vinyl containing group, an alkoxy-containing group, an alkyl-containing group, an acryloxy-containing group or a hydride-containing group. Further, in this aspect of the invention, n is an integer from 1 to about 20, and p is an integer from 1 to about 100,000.
In another aspect of the invention, there is provided a method of preparing a curable composition which includes the steps of reacting a first component having the structure:
with a second component having the structure:
to form a curable composition, which has the structure:
In this aspect of the invention, R 1 , R 2 , and R 3 may be the same or may be different, and may independently be a vinyl containing group, an alkoxy-containing group, an alkyl-containing group, an acryloxy-containing group or a hydride-containing group. n is an integer from 1 to about 10,000, and p is an integer from 1 to about 10,000.
In yet another aspect of the invention there is provided a method of preparing a curable composition which includes the steps of reacting a first component including the structure:
with a hydroxyalkylmethacrylate to form a curable composition having the structure:
In this aspect of the invention, R and R 2 may be the same or may be different, and may independently be a vinyl containing group, an alkoxy-containing group, an alkyl-containing group, an acryloxy-containing group or a hydride-containing group. R 3 is an alkylenyl group. Finally, n is an integer from 1 to about 20, and p is an integer from 1 to 4.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a graphic depiction of the curability of a composition within the scope of the present invention (Example 1) at temperatures of 50° C. and 80° C.
DETAILED DESCRIPTION OF THE INVENTION
Generally, the curable component has a backbone that may be based on silicone, urethene, polyalkylene, polyalkylene oxide, and combinations thereof, and pendant and/or terminating therefrom are reactive groups, desirably groups that will react to provide a heat-curable and/or moisture-curable group.
The term “cure” or “curing,” as used herein, refers to a change in state, condition, and/or structure in a material that is usually, but not necessarily, induced by at least one variable, such as time, temperature, moisture, radiation, presence and quantity in such material of a curing catalyst or accelerator, or the like. The terms cover partial as well as complete curing.
In a desirable aspect of the invention, the compositions are silicone-based, functionalized with at least one group selected from vinyl, alkoxy, alkyl, (meth)acryloxy, or hydride groups. While the invention is not limited to such types of materials, for the sake of convenience the invention will be described for the most part in these terms.
As used herein, the term “(meth)acrylate” is intended to refer to groups of the structure
where R 1 is H or alkyl. Acrylate, methacrylate and ethacrylate groups are merely a few examples of such (meth)acrylate groups.
As used herein, the terms “alkoxy group” and “aryloxy group” are intended to refer to groups of the structure, R—O, where R is alkyl or aryl, non-limiting examples of which include methoxy, ethoxy and phenoxy.
Curable Compositions
In one aspect of the invention, the curable composition provides a component of structure (I):
R 1 -A-R 2 (I)
where A is the backbone, and is either a hydrocarbon or heterohydrocarbon backbone having at least one pendent vinyl group, or is a siloxane backbone having at least one vinyl, alkoxy or hydride pendent group (depicted as R 1 and R 2 ).
In this aspect of the invention, R 1 and R 2 may either be the same or they may be different. They are independently selected from groups including a vinyl-containing group, an alkoxy-containing group, an alkyl-containing group, a (meth)acryloxy-containing group, and a hydride-containing group. The selection of the R 1 and R 2 groups may be limited, however. When A is a hydrocarbon or heterocarbon backbone having at lest one pendent vinyl group, R 1 and R 2 are desirably alkyl groups. When A is a siloxane backbone, having at least one pendent vinyl-containing group, then R 1 and R 2 are desirably a vinyl-containing group, an alkoxyl-containing group, or an alkyl-containing group. When A is a siloxane backbone, having at least one pendent hydride group, R 1 and R 2 are desirably a hydride-containing group, an alkyl-containing group, an alkoxy-containing group or a (meth)acryloxy-containing group.
In an alternative aspect of the invention, the curable composition may further include a catalyst. The catalyst is desirably a moisture cure catalyst, a heat cure catalyst, a light cure catalyst, and combinations of the various catalysts. In some embodiments, a peroxide can be a heat catalyst. In other embodiments, a hydrosilation catalyst may be effective in the presence of heat or at room temperature. In other embodiments, a metal catalyst, such as cobalt naphtenate, may be incorporated to polymerize the vinyl groups of the composition through interaction with atmospheric oxygen. In other embodiments, there may be anaerobic curing via a peroxide catalyst in the absence of oxygen.
In another aspect of the invention, there is provided an alternative curable composition. In this aspect of the invention, the curable composition provides a component of structure (II):
where R 3 may be the same or may be different in each occurrence, and includes alkyl groups having from 1 to about 4 carbons. R 4 may be a substituted or unsubstituted alkylenylsiloxy group, a substituted or unsubstituted alkylenyl(meth)acryloxy group, a substituted or unsubstituted alkylenylenoxy group, a substituted or unsubstituted alkylenyloximino group, or a substituted or unsubstituted alkylenylacetoxy group. R 5 is desirably a (meth)acryloxy group. R 6 is desirably an unsaturated group. R 7 and R 8 may be the same or they may be different, and they are independently any of the groups of R 3 , R 4 , R 5 and R 6 . n is an integer from 1 to about 12,000. m is an integer from 1 to about 20, and p is an integer from about 0 to about 20. In one desirable aspect of the invention, R 6 is a vinyl-containing group.
The present invention also provides a curable composition, which allows for moisture and/or heat curing. The composition includes a first component, which is a siloxane polymeric backbone having at least one vinyl group terminating at the end, and at least two pendent groups off of the polymeric backbone. Desirably, at least one of the pendent groups is a moisture-curing group, and at least one of the other pendent groups includes the structure:
R 1 , R 2 and R 3 may be the same or may be different. They may independently include a vinyl containing group, an alkoxy-containing group, an alkyl-containing group, an acryloxy-containing group and a hydride-containing group.
A non-limiting example of the curable component of the curable composition has the following structure:
In this structure, n is an integer from 1 to about 12,000, m may be an integer from 1 to about 20, and p may be an integer from 1 to about 20. However, the siloxane-vinyl containing group may be spaced randomly along the backbone of the structure, which may change the respective values of n and p.
Methods of Producing Curable Compositions
The present invention further provides various methods of producing curable compositions. The curable compositions prepared by the present invention allow for improved curing, either by moisture, heat, light, or combinations thereof.
In one aspect of the invention, there is provided a method of preparing a curable composition. First, there is provided a first component having the structure (I-A):
where n is an integer from 1 to about 12,000, m may be an integer from 1 to about 20, and p may be an integer from 1 to about 20. However, the siloxane-vinyl containing group may be spaced randomly along the backbone of the structure, which may change the values of n and p. In an alternate aspect of the invention, the side groups on the chain may include methoxy groups.
This first component (I-A) may either be manufactured by the user or obtained directly. In one aspect of the invention, the first component (I-A) may be manufactured by combining a structure (I-a):
HO—PDMS—OH (I-a)
with vinyl-trimethylsiloxane, to result in the first component (IA), set forth above. PDMS refers to polydimethylsiloxane.
The first component (IA) may then be combined with a hydride, having the structure (II-A):
where R 1A , R 2A and R 3A may be the same or they may be different. R 1A , R 2A and R 3A are each independently a vinyl-containing group, an alkoxy-containing group, an alkyl-containing group, an acryloxy-containing group or a hydride-containing group.
The resulting composition has the structure (III-A):
where R 1A , R 2A and R 3A may be the same or they may be different. R 1A , R 2A and R 3A are each independently a vinyl-containing group, an alkoxy-containing group, an alkyl-containing group, an acryloxy-containing group or a hydride-containing group. Additionally n is an integer from 1 to about 12,000, m may be an integer from 1 to about 20, and p may be an integer from 1 to about 20. However, the siloxane-vinyl containing group may be spaced randomly along the backbone of the structure, which may change the values of n and p.
In a desired aspect of the invention, the hydride (II-A) is combined with the first composition (I-A) in an amount that is insufficient to react fully with all available vinyl groups on the first composition (I-A). In an alternative aspect of the invention, the hydride may be added in a molar equivalent or higher, which will react with the side vinyl groups on the first composition (I-A), and further leave unreacted hydride monomers in the mixture.
In another aspect of the invention, there is a method of preparing a curable composition. There is provided a first component having the structure (I-B):
where R B , R 1B and R 2B may be the same or they may be different. R B , R 1B , and R 2B may each independently include a vinyl-containing group, an alkoxy-containing group, an alkyl-containing group, an acryloxy-containing group and a hydride containing group. n may be any integer from 1 to about 20. In a desired aspect of the invention, R 1B is a hydride-containing group.
In an alternate aspect of the invention, R 1B may be a hydride-containing group, and may be located anywhere on the backbone, including at one end as represented in (I-B). R 1B may alternatively include any structure that has at least one double bond and a moisture labile group on the silicone.
The first composition (I-B) may be reacted with a second component having the structure (II-B):
where R 3B is desirably an alkoxy-containing group.
The resulting composition includes the structure (III-B):
where R B , R 1B and R 2B may be the same or they may be different. R B , R 1B , and R 2B may each independently include a vinyl-containing group, an alkoxy-containing group, an alkyl-containing group, an acryloxy-containing group or a hydride containing group. R 3B is desirably an alkoxy-containing group. n may be any integer from 1 to about 20. In a desired aspect of the invention, R 1B is a hydride-containing group.
In an alternate aspect of the invention, R 1B may be a hydride-containing group, and may be located anywhere on the backbone, including at one end as represented in (I-B). R 1B may alternatively include any structure that has at least one double bond and a moisture labile group on the silicone.
In an alternative aspect of the invention, the second component (II-B) may be combined at a lower molar amount than the first component (I-B), to limit the reactivity of the components.
In another aspect of the invention, there is a method of preparing a curable composition. In this aspect of the invention, there is provided a first component having the structure (I-C):
where R C and R 1C are desirably substituted silanes. Desirably, R C and R 1C are trimethyl substituted silanes. p is an integer from 1 to about 100,000. n may be an integer from 1 to about 20. In an alternate aspect of the invention, n may be dispersed throughout the backbone of the polymer chain.
The first component (I-C) may then be reacted with a second component having the structure (II-C):
where R 2C , R 3C , and R 4C may be the same or may be different. R 2C , R 3C , and R 4C may each independently be a vinyl-containing group, an alkoxy-containing group, an alkyl-containing group, an acryloxy-containing group, or a hydride-containing group.
The resulting curable composition has the structure (III-C):
where R C and R 1C are desirably substituted silanes. Desirably, R C and R 1C are trimethyl substituted silanes. R 2C , R 3C , and R 4C may be the same or may be different. R 2C , R 3C , and R 4C may each independently be a vinyl-containing group, an alkoxy-containing group, an alkyl-containing group, an acryloxy-containing group, or a hydride-containing group. p is an integer from 1 to about 100,000. n may be an integer from 1 to about 20. In an alternate aspect of the invention, n may be dispersed throughout the backbone of the polymer chain. In one aspect of the invention, the end groups of (III-C) may be alkyl-containing groups.
In an alternative aspect of the invention, the second component (II-C) may be combined at a lower molar amount than the first component (I-C), to limit the reactivity of the components.
In another aspect of the invention, there is a method of preparing a curable composition. There is provided a first component, which has the structure (I-D):
where n is any integer from 1 to about 10,000 and p is an integer from 1 to about 10,000.
The first component (I-D) may then be reacted with a second component having the structure (II-D):
where R 1D , R 2D and R 3D may be the same or may be different. They may independently be a vinyl-containing group, an alkoxy-containing group, an alkyl-containing group, an acryloxy-containing group and a hydride-containing group.
The resulting curable composition has the structure (III-D):
where R 1D , R 2D and R 3D may be the same or may be different. They may independently be a vinyl-containing group, an alkoxy-containing group, an alkyl-containing group, an acryloxy-containing group and a hydride-containing group, and where n is an integer from 1 to about 10,000, and where p is an integer from 1 to about 10,000.
In an alternative aspect of the invention, the second component (II-D) may be combined at a lower molar amount than the first component (I-D), to limit the reactivity of the components.
In another aspect of the invention, a method of preparing a curable composition is provided. There is provided a first composition having the structure (I-E):
where R E and R 2E may be the same or may be different. R E and R 2E are independently selected from vinyl-containing groups, alkoxy-containing groups, alkyl-containing groups, acryloxy-containing groups and hydride-containing groups. n may be an integer from 1 to about 20. The first composition may be combined with a hydroxyalkylmethacrylate to form a curable composition having the structure (II-E):
where R E and R 2E may be the same or may be different. R E and R 2E are independently selected from vinyl-containing groups, alkoxy-containing groups, alkyl-containing groups, acryloxy-containing groups and hydride-containing groups. n may be an integer from 1 to about 20. p may be an integer from 1 to 4, and r 3E may be an alkylenyl-containing group.
In an aspect of the invention, the hydroxyalkylmethacrvlate may have the structure (III-E):
where R 3E may be an alkylenyl-containing group and p may be an integer from 1 to 4.
As described above, the polysiloxanes may be optionally grafted with heat curable groups, moisture curable groups, or light curable groups. Non-limiting examples of heat curable groups include alkenes, including vinyl or allyl alkenes, or any double bond entity. In one embodiment, the heat curable groups may include a (meth)acrylate functional group.
Non-limiting examples of moisture curable groups include organic compounds of titanium, tin, zirconium and of course combinations thereof. Illustrative examples of the titanium compounds include tetraisopropyl titanate and tetrabutyl titanate. Illustrative examples of the tin compounds include dibutyltin dilaurate, dibutyltin diacetate, dioctyltindicarboxylate, dimethyltindicarboxylate, and dibutyltindioctoate. Zirconium compounds include zirconium octanoate, and zinc compounds include 2-ethylhexanoate. Additionally, organic amines such as tetramethylguandinamines, diazabicyclo[5.4.0]undec-7-ene (DBU), triethylamine, and the like may be used. See also U.S. Pat. No. 4,111,890, the disclosure of which is expressly incorporated herein by reference.
Non-limiting examples of light curable groups include any photoinitiator known in the art to cure acrylic functionalities, including benzoin and substituted benzoins (such as alkyl ester substituted benzoins), Michler's ketone, dialkoxyacetophenones, such as diethoxyacetophenone (“DEAP”), benzophenone and substituted benzophenones, acetophenone and substituted acetophenones, and xanthone and substituted xanthones. Desirable photoinitiators include DEAP, benzoin methyl ether, benzoin ethyl ether, benzoin isopropyl ether, diethoxyxanthone, chloro-thio-xanthone, azo-bisisobutyronitrile, N-methyl diethanolaminebenzophenone, and mixtures thereof. Visible light initiators include camphoquinone, peroxyester initiators and non-fluorene-carboxylic acid peroxyesters.
Commercially available examples of photoinitiators include those from Vantico, Inc., Brewster, New York under the IRGACURE and DAROCUR tradenames, specifically IRGACURE 184 (1-hydroxycyclohexyl phenyl ketone), 907 (2-methyl-1-[4-(methylthio)phenyl]-2-morpholino propan-1-one), 369 (2-benzyl-2-N,N-dimethylamino-1-(4-morpholinophenyl)-1-butanone), 500 (the combination of 1-hydroxy cyclohexyl phenyl ketone and benzophenone), 651 (2,2-dimethoxy-2-phenyl acetophenone), 1700 (the combination of bis(2,6-dimethoxybenzoyl-2,4,4-trimethyl pentyl) phosphine oxide and 2-hydroxy-2-methyl-1-phenyl-propan-1-one), and 819 [bis(2,4,6-trimethyl benzoyl)phenyl phosphine oxide] and DAROCUR 1173 (2-hydroxy-2-methyl-1-phenyl-1-propane) and 4265 (the combination of 2,4,6-trimethylbenzoyldiphenyl-phosphine oxide and 2-hydroxy-2-methyl-1-phenyl-propan-1-one); and IRGACURE 784DC (bis(η 5 -2,4-cyclopentadien-1-yl)-bis[2,6-difluoro-3-(1H-pyrrol-1-yl)phenyl]titanium).
Particularly desirable photoinitiators include DEAP. Generally, the amount of photoinitiator should be in the range of about 0.1% to about 10% by weight, such as about 2 to about 6% by weight.
The polysiloxanes may additionally include flame-retardant components in an amount effective to enhance the resistance of the composition to flammability and combustion. Typically, the flame-retardant component should be present in an amount up to about 70% by weight, with 20-60% by weight being particularly desirable to achieve the desired affect.
Suitable flame-retardant components include hydrated aluminas, precipitated silicas (such as those available commercially under the AEROSIL tradename from Degussa Corporation), hydrated zinc borates (such as those available commercially under the FIREBREAK ZB tradename from Harwick Standard Distribution Corp.), and combinations thereof.
A further component which may optionally be included in the inventive compositions is a reactive diluent, such as (meth)acrylates, for instance those represented by H 2 C═CGCO 2 R 6 , where G may be hydrogen, halogen or alkyl of 1 to about 4 carbon atoms, and R 6 may be selected from alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkaryl, aralkyl or aryl groups of 1 to about 16 carbon atoms, any of which may be optionally substituted or interrupted as the case may be with silane, silicon, oxygen, halogen, carbonyl, hydroxyl, ester, carboxylic acid, urea, urethane, carbamate, amine, amide, sulfur, sulonate, sulfone and the like. Alternative diluents include, without limitation, vinyl trimethoxysilane; alkyl acetates; hydrocarbon solvents, such as toluene; and acrylamides, such as N,N-dimethyl acrylamide. Other useful additives include plasticizers, fillers such as silica, viscosity modifiers, flow modifiers, pigments, antioxidants, stabilizers, inhibitors, adjuvants, catalysts, accelerators, thixotropic agents, and combinations thereof. These additives should be present in amounts suitable to effectuate their intended purpose.
The compositions of the invention may also include other ingredients to modify the cured or uncured properties as desired for specific applications. For instance, adhesion promoters, such as (meth)acryloxypropyltrimethoxysilane, trialkyl- or triallyl-isocyanurate, glycidoxypropyl trimethoxysilane, vinyl trimethoxysilane and the like, may be incorporated at levels up to about 5 weight percent.
The plasticizers may be present at levels of up to about 30 weight percent. An example of a plasticizer is a non-(meth)acrylated silicone, such as trimethylsilyl-terminated oils of 100-500 csp viscosity and silicone gums. The non-(meth)acrylated silicones may include co-curable groups, such as vinyl groups.
The trimethylsilyl-terminated oils include trimethylsilyl-terminated polydimethylsiloxanes having a viscosity within the range of between about 100 and 5,000 cps.
The physical characteristics of cured reaction products obtained from a given composition will depend in part on the type, identity, amount and molecular weight of the curable component.
The following example is illustrative of the invention.
EXAMPLE
Example 1
30 grams of polydimethylsiloxane with hydride pendant groups was mixed with 30 grams of vinyl trimethoxy silane. The reaction was initiated by the addition of 0.1 grams of a platinum catalyst. The resulting product, cyclotri(vinyl methyl siloxane) was used for the experimental testing.
A Thermo Nicolet Nexus 470 spectrometer with a CIC Photonics Explorer horizontal ATR accessory was used to monitor the disappearance of the C═C bond in the product. The product was placed on an ATR crystal (45° zinc selenide crystal) of a horizontal attenuated total reflectance accessory and a spectrum was taken. The catalyst was then added and another spectrum was taken one minute later. The formulation was then placed in an oven maintained at a temperature of 80° C., and a spectrum was taken every 15 minutes for up to 150 minutes. A separate formulation was placed in an oven maintained at a temperature of 50° C., with the same spectrum being taken every 15 minutes up to 1500 minutes.
For the analysis, a peak area of C═C stretch between 2863 and 2820 cm −1 was used as the internal standard. The reaction was monitored by examining the integrated peak area of the C═C in the formulation. The disappearance of the C═C bond was calculated as follows:
% disappearance= A 0 −A t /A 0
where A 0 is the ratio of the area of the C═C peak and the area of the internal standard peak before the reaction started. At is the ratio of the area of the same two peaks at time t.
The tables below show the results of the spectrum measurements. Table I shows the C═C disappearance % at 80° C., and Table II shows the C═C disappearance % at 50° C. As can be seen, at 80° C., the C═C disappearance reached over 90% after only 60 minutes, while at 50° C., the C═C disappearance reached 75% after 165 minutes, and only reached 81% after 1110 minutes. At 50° C., the maximum disappearance seen was 82% after 1500 minutes.
TABLE I
(disappearance % at 80° C.)
Internal
Standard
%
Condition
C═C
(IS)
C═C/IS
change
Before catalyst was added
0.1073
0.771
0.13917
0
1 minute after catalyst
0.0918
0.667
0.137631
1
added
15 mins after catalyst added
0.0244
0.8133
0.030001
78
30 mins after catalyst added
0.01808
0.6073
0.029771
79
45 mins after catalyst added
0.034
1.079
0.031511
77
60 mins after catalyst added
0.0129
1.1806
0.010927
92
75 mins after catalyst added
0.0126
0.8911
0.01414
90
90 mins after catalyst added
0.012
0.985
0.012183
91
150 mins after catalyst added
0.018
1.3023
0.013822
90
TABLE II
(disappearance % at 50° C.)
Internal
Standard
%
Condition
C═C
(IS)
C═C/IS
change
Before catalyst was added
0.1073
0.771
0.13917
0
1 minute after catalyst
0.0918
0.667
0.137631
1
added
15 mins after catalyst added
0.04985
0.634
0.078628
44
30 mins after catalyst added
0.0597
0.919
0.064962
53
45 mins after catalyst added
0.0444
0.795
0.055849
60
60 mins after catalyst added
0.059
1.045
0.056459
59
75 mins after catalyst added
0.0636
1.358
0.046834
66
90 mins after catalyst added
0.0514
1.0521
0.048855
65
105 mins after catalyst added
0.03767
0.813
0.046335
67
120 mins after catalyst added
0.0384
0.8789
0.043691
69
135 mins after catalyst added
0.0357
0.88
0.040568
71
150 mins after catalyst added
0.0393
0.9495
0.04139
70
165 mins after catalyst added
0.0436
1.274
0.034223
75
180 mins after catalyst added
0.0344
1.0764
0.031958
77
195 mins after catalyst added
0.0349
1.099
0.031756
77
210 mins after catalyst added
0.0307
0.9739
0.031523
77
1110 mins after catalyst added
0.0305
1.168
0.026113
81
1500 mins after catalyst added
0.025
0.9886
0.025288
82
FIG. 1 shows a graphic comparison of the results obtained at temperatures of 80° C. and at 50° C. As can be seen in the results, the inventive formulation shows a much greater, faster and more complete C═C disappearance at a higher temperature. | This application relates to polysiloxane compositions grafted with improved heat curable, moisture curable, or heat/moisture curable groups. In particular, the polysiloxane compositions have reactive groups on the terminal or pendent areas of the siloxane backbone, which once reacted provide improved heat and/or moisture curable polysiloxanes. | 2 |
BACKGROUND OF THE INVENTION
[0001] The present invention relates to metallo-organic cobalt compounds and their use in the prophylactic treatment of subjects to prevent chlamydia infections.
[0002] It has been discovered that certain conditions and diseases, e.g., inflammation, burns, wounds, and diseases caused by bacteria, fungi and viruses in mammalian species can be treated with certain complexes of cobalt having the structure:
[0003] wherein each A may be the same or different and is an alkyl group, a phenyl group or a substituted derivative of a phenyl group;
[0004] wherein each Y may be the same or different and is hydrogen, an unbranched alkyl group, a halide or a group having the structure
[0005] wherein R is hydrogen, an alkoxide group, and alkyl group, or OH;
[0006] wherein each B may be the same or different and each is hydrogen or an alkyl group;
[0007] wherein each X may be the same or different and each is a water soluble group having weak to intermediate ligand filed strength; and
[0008] Z — is a soluble, pharmaceutically acceptable negative ion.
[0009] Today, chlamydia infections are known to be significant causes of morbidity in human and veterinary medicine. Many of these infections present no noticable symptoms, yet can lead to sterility. New prophylactic treatments would decrease the incidence of these infections and improve overall health.
SUMMARY OF THE INVENTION
[0010] We have discovered a prophylactic use for the series of compounds having the structure:
[0011] wherein
[0012] each A may be the same or different and is an alkyl group, a phenyl group or a substituted derivative of a phenyl group;
[0013] each Y may be the same or different and is hydrogen, an unbranched alkyl group, a halide or a group having the structure
[0014] wherein R is hydrogen, an alkoxide group, an alkyl group, or OH;
[0015] each B may be the same or different and each is hydrogen or an alkyl group;
[0016] Z — is a soluble, pharmaceutically acceptable negative ion; and
[0017] each X may be the same or different and is an axial ligand selected from the group consisting of moieties having the formula:
[0018] wherein R 1 , R 2 , R 3 , and R 4 may be the same or different and maybe hydrogen or lower alkyl having from 1 to 4 carbon atoms; and
[0019] wherein R 5 , R 6 , R 7 , R 8 and R 9 may be the same or different and may be selected from the group consisting of electron donating groups and electron withdrawing groups;
[0020] with the proviso that R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are of a sufficiently small size so as not to prohibit the attachment of the axial ligand to the Co atom due to steric hindrance.
[0021] As used herein, the term “axial” when used in conjunction with the term “ligand” refers to the fact that the ligand is oriented outside the plane of the molecule and has the same meaning as described in connection with FIG. 1 of U.S. Pat. No. 5,049,557. As used herein, and unless otherwise indicated, an alkyl group means a linear, branched or cyclic alkyl group containing from one to six carbon atoms.
[0022] The compounds having the structure of Formula II exhibit prophylactic efficacy when applied as a topical composition to the contact site prior to contact with chlamydia and/or by inactivating chlamydia exposed to the composition. The compositions of the invention may further be used for antisepsis or disinfection of surfaces, such as, surgical tools or preparations such as, media or blood-derived products, which are contaminated with chlamydia.
DETAILED DESCRIPTION OF THE INVENTION
[0023] The compounds used in the present invention may be crystallized with numerous counter-anions. Counter-anions which are pharmaceutically acceptable and are water soluble, such as, halide ions, PF 6 — and BF 4 — , are preferred. The bromide and chloride salts of the present compounds are the most preferred because they are more water soluble than other salts of the compounds.
[0024] As discussed above, A may be an alkyl group, a phenyl group or a substituted derivative of a phenyl group. Preferably, the alkyl group is a C 1 -C 5 group with methyl, ethyl, and butyl groups being particularly preferred. Suitable substituted derivatives of the phenyl group are derivatives wherein each substituent is a halide, an alkyl group or a group having the structure
[0025] wherein R is hydrogen, an alkoxide group, an alkyl group or an OH group. To date, the most useful derivatives have proven to be those in which the substituents are halides, or alkyl groups.
[0026] Y may be hydrogen, an unbranched alkyl group, a halide or a group having the structure
[0027] wherein R is hydrogen, an alkoxide group, an alkyl group or an OH group. In certain embodiments, it is preferred that Y is chlorine, a hydrogen atom or a C 1 -C 3 alkyl group. In embodiments where Y has a structure
[0028] ,it is preferred that R is hydrogen, a methyl group or an OH group.
[0029] B may be hydrogen or an alkyl group, and preferably is a C 1 -C 3 alkyl group.
[0030] X may be imidazole or pyridinyl groups linked to the cobalt atom through a nitrogen of the ring. The imidazole or pyridinyl nuclei may have hydrogen atoms, or electron donating or withdrawing groups substituted thereon.
[0031] The electron withdrawing or donating groups which may constitute appendant groups R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are those known in the art to exert the specified electron withdrawing or donating effects on aromatic nuclei. Typical of electron donating groups are NO 2 — , Cl — , Br — , and the like. The identity of the particular group is not crucial so long as it does not impart properties to the molecules which are detrimental to the desired properties of the compound, e.g., decreased antiviral activity, increased toxicity, and the like. Additionally, the group must not be so large as to prevent the axial ligand to attach to the cobalt atom due to steric effects, e.g., steric hindrance.
[0032] Preferably, the groups attached to the imidazole nucleus are alkyl having from one to three carbon atoms. Of these, methyl and ethyl are most preferred. Preferred are the unsubstituted, 2-methyl, 4-methyl, and 2-ethyl imidazoles and the unsubstituted pyridinyl.
[0033] The following Table provides the structures of preferred compounds in accordance with the present invention. Compound 23, which is disclosed in U.S. Pat. No. 5,142,076 as exhibiting antiviral activity, is included as a comparison in the examples that follow.
[0034] In the following diagram, B is, in each case, methyl, and A, Y, X and Z — refer to those symbols as used in structure II.
COMPOUND Y X Z A 23 H —NH 3 Cl —CH 3 76 H Br —CH 3 82 H Cl CH 3 93 Cl Br —CH 3 96 H Br —CH 3 97 H Br —CH 3 98 H Br C 6 H 5 100 Cl Br —CH 3 101 Cl Br —CH 3 102 H Cl C 6 H 5 109 H Cl —CH 3
[0035] “Chlamydia” is used herein to mean any one or more of the bacteria in the genus chlamydia. The genus chlamydia includes the species C. pneumoniae, C. psittaci and C. trachomatis.
[0036] The compositions used in the instant invention include a pharmaceutically acceptable carrier and a compound as defined above in a chlamydia prophylactic effective amount. As used herein, the expressions chlamydia prophylactic effective amount, dosage or regimen mean that amount, dosage or regimen which results in a sufficient concentration of the particular compound at an appropriate site to reduce the risk of infection by chlamydia. By appropriate site, it is meant a site which potentially contains chlamydia or is an area of a subject of potential exposure to chlamydia or is an area of a subject that has been exposed to chlamydia but as a result of such exposure, the subject has not yet acquired chlamydia disease. As used herein, the expression acquired chlamydia disease means that the subject, in fact, has the disease and can no longer be treated prophylactically to reduce the risk of infection by chlamydia, but, rather, must be treated therapeutically to cure, ameliorate or reduce the effects of the disease.
[0037] For topical administration, the inventive composition may be placed in a pharmaceutically acceptable aqueous solution, ointment, salve, cream or the like. The compounds used in the present invention are water soluble, although the degree of solubility may vary from compound to compound, and may be dissolved in a number of conventional pharmaceutically acceptable carriers. Suitable carriers include polar, protic solvents, such as, water, or normal saline, or non-polar solvents, lipids and the like. The compounds may also be suspended in a suspension medium that is not miscible with water, for example, petrolatum, or may be formulated in an emulsion (water-in-oil or oil-in-water).
[0038] When the compounds of formula II are to be administered by the topical route for prevention of infection, i.e., prophylaxis or disinfection, their concentration in an aqueous solution, ointment, salve, creme, or the like can vary from about 0.00005% to about 5% by weight. A preferred concentration range lies between about 0.0005% and about 2% by weight. A particularly preferred concentration range is from about 0.5% to about 2%. Typically, the topical composition shows prophylactic effect when applied to the contact site from about 1 hour before contact with chlamydia to about 6 hours after contact with chlamydia. Preferably, the topical composition is applied within five minutes of contact with chlamydia. More particularly, the inventive compositions can be applied intravaginally for the prevention of sexually transmitted diseases. The topical composition containing the inventive compound could, for example, be applied with an applicator or an intravaginal device or the topical composition could be coated on a condom or other sexual barrier devices.
[0039] When the compounds of formula II are to be used for disinfecting liquid preparations, such as, media, blood-derived products or the like, their concentration in the liquid preparations is from about 0.005% to about 5% by weight. A preferred concentration range lies between about 0.05% and about 5% by weight. A most preferred concentration range lies between about 0.01% and about 2% by weight.
[0040] General methods for the synthesis of the compounds of the present invention are described in U.S. Pat. No. 5,049,557, referred to and incorporated by reference hereinabove. As noted therein, the reaction of Co(II) complexes with molar oxygen has been studied extensively (see, R. S. Drago and B. R. Corden, Acc. Chem. Res., 1980, 13, 353 & E. C. Niederhoffer, J. H. Timmons and A. E. Martell, Chem. Rev. 1984, 84, 137). Normally, cobalt (II) forms 2:1 peroxo bridged complexes in aqueous solutions (see E. C. Niederhoffer, J. H. Timmons and A. E. Martell, Chem. Rev. 1984, 84, 137). In recent years, a number of Co(II) complexes have been reported to give 1:1 cobalt-oxygen adducts at room temperature. These complexes usually contain ligands which when bound to Co(II) give rise to a low spin planar geometry. Addition of base and O 2 to these complexes leads to the formation of octahedral complexes where the base and the O 2 occupy axial positions (see, A. Summerville, R. D. Jones, B. M. Hoffman and F. Basolo, J.Chem. Educ., 1979, 56, 3, 157).
[0041] On the basis of measurements utilizing a variety of physical techniques, it is now a well-accepted fact that the most accurate electronic structure description of the CO:O 2 moiety is a Co(III) ion bound to O 2 — where the actual amount of Co→O 2 electron transfer depends on the nature of the ligand and the donor set (see, A. Summerville, R. D. Jones, B. M. Hoffman and F. Basolo, J. Chem. Educ. 1979, 56, 3 157, & D. Getz, E. Malmud, B. L. Silver and Z. Dori, J. Am Chem. Soc., 1975, 97, 3846). It has been shown that electron transfer increases with increase of the ligand field strength (see, R. S. Drago and B. R. Corden, Acc. Chem. Res., 1980, 13, 353). This can be easily understood from the molecular orbital diagram depicted in FIG. 1 of U.S. Pat. No. 5,049,557 and the description therein.
[0042] The following examples are provided to assist in further understanding the present invention. The particular materials and conditions employed are intended to be further illustrative of the invention and are not limiting upon the reasonable scope thereof.
EXAMPLE 1
[0043] Compounds for use with the present invention can be prepared by the following general procedure. In particular, a cobalt-II complex is prepared by mixing equimolar amounts of the N,N′-bisethylenediimine ligands, e.g., L23 and the like as disclosed in U.S. Pat. No. 5,049,557, with cobalt acetate in methanol under nitrogen. About 2.2 equivalents of the desired axial ligand is added followed by oxidation. The desired product may then be precipitated by the addition of a saturated aqueous solution of sodium chloride or sodium bromide followed by recrystallization from an ethanol-water solution.
[0044] Compound 96 (having bromide as the counterion) was synthesized as follows:
[0045] A 3-neck flask equipped with a nitrogen bubbler and a 2 liter dropping funnel was charged with 112 grams (0.5 moles) of the ligand (L23 or N,N′bis-(acetylacetone) ethylene-diimine) in 500 ml of absolute methanol. To the ligand solution is added 125 grams (0.5 moles) of cobalt acetate tetrahydrate dissolved in 1.5 liters of degassed methanol. The reaction mixture is stirred for 2 hours and then refluxed for 15 minutes on a hot water bath. An orange solution results to which 90 grams (1.1 moles) of 2-methyl imidazole dissolved in 100 ml of methanol are added. The reaction mixture is exposed to the open air while maintaining vigorous stirring. Ten grams of activated charcoal are added to the stirring mixture and the oxidation is continued overnight.
[0046] The mixture is then filtered and 50 grams of sodium bromide dissolved in a minimum amount of water is added to the filtered brown solution. The solution obtained is concentrated and allowed to crystallize. The crude product is recrystallized from hot ethanol-water solution by standing at room temperature or a lower temperature. The purity of the product is checked by elemental analysis, electronic spectra and NMR.
EXAMPLE 2
[0047] [0047] C. trachomatis elementary bodies were incubated for four hours on ice with different concentrations of Compound 96. At the end of that time, serial dilutions were performed on McCoy cell monolayers and the plates were incubated for two days, after which, C. trachomatis titers were enumerated.
[0048] When C. trachomatis was incubated with 5 mg/mL Compound 96, no inclusion bodies were detected. When the Compound 96 concentration was reduced to 0.5 mg/mL, there was a 93% reduction in the number of inclusion forming units. At 0.05 and 0.005 mg/mL Compound 96, the inhibitory effect was lost.
EXAMPLE 3
[0049] In a study of the mouse model, chlamydia infection was greatly reduced and hydrosalpingitis completely blocked by topical application of Compound 96 prior to challenge with chlamydia. Seventy-eight female Swiss Webster mice were pretreated with medroxyprogesterone acetate and were randomized into three groups to receive either saline (control) (24 mice), 0.5% Compound 96 (27 mice), or 2.0% Compound 96 (27 mice). The animals were anesthetized by intraperitoneal injection of sodium pentabarbital and then the vagina of each animal was swabbed with a moistened calcium alginate tipped swab. The animals were administered 15 μl of control or test compound intravaginally in one treatment. Twenty seconds later, they were challenged by intravaginal instillation with 15 μl of a suspension containing 5.0 log 10 infection forming units C. trachomatis mouse pneumonitis biovar (MoPn). Vaginal swabs were collected on days 3, 6 and 10 post-challenge to assess the effect of treatment on vaginal replication in the genital tract. In addition, on day 10, approximately half of the animals from each group were sacrificed, the upper genital tract harvested and the magnitude of chlamydia infection determined by quantitative culture. The remaining animals were sacrificed on day 35 post-challenge and the upper genital tract examined for evidence of hydrosalpingitis.
[0050] Outcome data for the study is presented in Table 1 below. All of the saline treated control animals developed lower tract infection which spread to the upper genital tract in all animals sacrificed on day 10 post-challenge. Treatment with 0.5% Compound 96 significantly reduced the number of animals which experienced lower genital tract replication but did not impact spread to the upper genital tract. In contrast, treatment with 2% Compound 96 significantly reduced the incidence of isolation of MoPn from both the lower and upper genital tract with the 3 animals that experienced lower tract replication being the only animals in which the organism was isolated from the upper genital tract. Quantitative culture data for Compound 96 treated animals from which the organism was isolated indicated that the titer of MoPn was not significantly reduced. Among animals that were sacrificed on day 35 post-challenge, 50% of controls had hydrosalpingitis in at least one of the oviducts. The incidence was not significantly reduced in animals that received 0.5% Compound 96, but again, 2% Compound 96 proved effective with none of the animals having hydrosalpingitis in either oviduct.
[0051] Table 1 below shows the effect of Compound 96 against genital chlamydia infection in a mouse model.
TABLE 1 Replication in Replication in Incidence Lower Tract Upper Tract of Group Having: Incidence a D3 Titer b Incidence c Titer d Hydrosalpingitis e Saline administered 24/24 2.9 ± 0.1 12/12 2.4 ± 0.1 6/12 0.5% Compound 96 21/27 f 2.8 ± 0.1 13/15 2.4 ± 0.1 5/12 administered 2.0% Compound 96 3/27 g 3.7 ± 0.1 3/16 g 2.7 ± 0.1 0/11 f administered
EXAMPLE 4
[0052] In another study of the mouse model, chlamydia infection was also greatly reduced by topical administration of Compound 96 prior to chlamydia challenge. Forty-eight Swiss Webster mice were pretreated with medroxyprogesterone acetate and were randomized into three groups to receive either saline (control) or 2.0% of Compound 96. In particular, sixteen mice received saline (control) twenty seconds prior to chlamydia challenge, sixteen mice received 2.0% Compound 96 five minutes prior to chlamydia challenge, and sixteen mice received 2.0% Compound 96 twenty seconds prior to chlamydia challenge.
[0053] The mice were anesthetized by intraperitoneal injection of sodium pentabarbital and then the vagina of each mouse was swabbed with a moistened calcium alginate tipped swab. The mice were then administered 15 μl of control or test compound intravaginally in one treatment. Either twenty seconds or five minutes later, they were challenged by intravaginal instillation with 15 μl of a suspension containing 5.0 log 10 infection forming units C. trachomatis mouse pneumonitis biovar (MoPn). Vaginal swabs were collected on days 3 and 6 post-challenge to assess the effect of treatment on vaginal replication in the genital tract. In addition, on day 10, the mice were sacrificed and the upper genital tract harvested and cultured to determine whether the mice had experienced ascending infection. The results are shown below in Table 2.
TABLE 2 Number Protected Number Protected Number Against in Against in Group Having: in group Lower Tract Upper Tract Saline administered 16 0 (0%) 0 (0%) 5 minutes prior to challenge 2% Compound 96 16 5 (31%) h 6 (38%) h administered 5 minutes prior to challenge 2% Compound 96 16 14 (88%) i 14 (88%) i administered 20 seconds prior to challenge
[0054] As in Example 3, all of the saline treated control mice developed lower and upper tract infection. Treatment with 2% Compound 96 twenty seconds prior to challenge provided good protection of both upper and lower genital tracts. The protection seen when Compound 96 was administrated five minutes before challenge was not as good as Compound 96 administrated twenty seconds prior to challenge. However, treatment with 2% Compound 96 five minutes before challenge significantly reduced the number of mice with lower and upper tract infection.
[0055] Thus, while there have been described what are presently believed to be the preferred embodiments of the present invention, those skilled in the art will realize that other and further embodiments can be made without departing from the spirit and scope of the invention, and it is intended to include all such further modifications and changes as come within the true scope of the invention. | The likelihood of chlamydia infection can be prevented by the topical application of metallo-organic cobalt compounds according to the following formula to the site of infection:
wherein each A may be the same or different and is an alkyl group, a phenyl group or a substituted derivative of a phenyl group; each Y may be the same or different and is hydrogen, an unbranched alkyl group, a halide or a group having the structure wherein R is hydrogen, an alkoxide group, and alkyl group, or OH; each B may be the same or different and each is hydrogen or an alkyl group; each X may be the same or different and each is a water soluble group having weak to intermediate ligand filed strength; and Z — is a soluble, pharmaceutically acceptable negative ion. Metallo-organic cobalt compounds may also be used to disinfect liquids which contain chlamydia. | 0 |
RELATED APPLICATIONS
This application is a nationalization of PCT Application No. PCT/JP02/11036 filed Oct. 24, 2002. This application claims priority from Japanese Patent Application No. 2001-327019 filed on Oct. 24, 2001.
1. Technical Field
The present invention relates to a method for producing an optically active 3,5-dihydroxyhexanoic acid derivative. In particular, it relates to a method for producing the optically active 3,5-dihydroxyhexanoic acid derivative by stereoselectively reducing a carbonyl group of an optically active 3-oxo-5-hydroxyhexanoic acid derivative.
The optically active 3,5-dihydroxyhexanoic acid derivative is suitable for use as a drug intermediate, in particular an intermediate for HMG-CoA reductase inhibitors.
2. Background Art
In producing an optically active 3,5-dihydroxyhexanoic acid derivative by stereoselectively reducing a carbonyl group of an optically active 3-oxo-5-hydroxyhexanoic acid derivative, the following methods have been conventionally employed:
(1) a method for producing an optically active 3,5,6-trihydroxyhexanoic acid derivative by stereoselectively reducing an optically active 3-oxo-5,6-dihydroxyhexanoic acid derivative in the presence of sodium borohydride and triethylborane (Japanese Unexamined Patent Application Publication No. 2-262537); (2) a method for producing optically active 6-benzyloxy-3,5-dihydroxyhexanoic acid through asymmetric hydrogenation of 6-benzyloxy-5-tetrahydropyranyloxy-3-oxohexanoic acid tert-butyl ester catalyzed by Ru 2 Cl 4 [BINAP] 2 N(CH 2 CH 3 ), which is a ruthenium-optically active phosphine complex (Japanese Unexamined Patent Application Publication No. 6-65226); (3) a method including asymmetric hydrogenation of 6-tert-butoxy-5-hydroxy-3-oxohexanoic acid tert-butyl ester using the same catalyst as in (2) above (Japanese Unexamined Patent Application Publication No. 2-289537); (4) a method for producing an optically active 2,4-dihydroxyadipinic acid derivative by stereoselectively reducing an optically active 4-oxo-2-hydroxyadipinic acid derivative in the presence of sodium borohydride and triethylborane (Japanese Unexamined Patent Application Publication No. 4-69355; and (5) a method for producing an optically active 2,4-dihydroxyadipinic acid derivative by stereoselectively reducing an optically active 4-oxo-2-hydroxyadipinic acid derivative in the presence of microorganisms (Japanese Unexamined Patent Application Publication No. 5-308977).
In the methods of paragraphs (1) and (4) employing sodium borohydride, the reaction must be carried out under ultralow temperatures of about −80° C. to yield high stereoselectivity; moreover, these methods are cost-ineffective due to the use of relatively expensive reagents. The method of paragraph (5) employing microorganisms requires an incubator and treatment of reaction solutions. In the method of paragraph (2), the 5-position hydroxy is protected to yield high stereoselectivity; accordingly, introduction and extraction of protective groups are necessary. In the method of paragraph (3), the 5-position hydroxy is unprotected, but the reaction is carried out under a high hydrogen pressure of 50 kg/cm 2 ; moreover, the reaction yield and selectivity are far from satisfactory.
SUMMARY OF INVENTION
The present invention provides a simple and cost-effective method for producing an optically active 3,5-dihydroxyhexanoic acid derivative, the method requiring neither ultralow-temperature reaction equipment, culture equipment, nor protection of the 5-position.
The present inventors have conducted extensive investigations to solve the problem of the related art and found that an optically active 3,5-dihydroxyhexanoic acid derivative can be synthesized by asymmetric hydrogenation of an optically active 3-oxo-5-hydroxyhexanoic acid derivative using inexpensive hydrogen as the reductant. The asymmetric hydrogenation is catalyzed by a ruthenium-optically active phosphine complex, in particular, a RuBr 2 BINAP complex prepared from optically active 2,2′-bisdiarylphosphino-1,1′-binaphthyl (BINAP) and a ruthenium complex.
In particular, the present invention provides a method for producing an optically active 3,5-dihydroxyhexanoic acid derivative represented by formula (1):
(wherein R 1 is C 1 –C 10 alkyl, C 7 –C 20 aralkyl, or C 6 –C 20 aryl, and R is
wherein R 2 is C 1 –C 10 alkyl, C 7 –C 20 aralkyl, or C 6 –C 20 aryl; R 3 s are each independently C 1 –C 10 alkyl, C 7 –C 20 aralkyl, or C 6 –C 20 aryl, or together form C 1 –C 10 alkylene; and R 4 is C 1 –C 10 alkyl, C 7 –C 20 aralkyl, or C 6 –C 20 aryl), the method including a step of conducting asymmetric hydrogenation of an optically active 3-oxo-5-hydroxyhexanoic acid derivative represented by formula (2) in the presence of a ruthenium-optically active phosphine complex as a catalyst:
(wherein R and R 1 are the same as described above).
The present invention also relates to the above-described method in which the ruthenium-optically active phosphine complex is a RuBr 2 BINAP complex prepared from 2,2′-bisdiarylphosphino-1,1′-binaphthyl and a ruthenium complex.
The present invention also relates to the method for producing an optically active 3,5,6-trihydroxyhexanoic acid derivative represented by formula (4)
(wherein R 1 and R 4 are the same as above) through asymmetric hydrogenation of an optically active 3-oxo-5,6-dihydroxyhexanoic acid derivative represented by formula (3)
(wherein R 1 and R 4 are the same as above)
The present invention also relates to the method for producing an optically active 2,4-dihydroxyadipinic acid derivative represented by formula (6)
(wherein R 1 and R 2 are the same as above) through asymmetric hydrogenation of an optically active 4-oxo-2-hydroxyadipinic acid derivative represented by formula (5)
(wherein R 1 and R 2 are the same as above)
The present invention also relates to the method for producing an optically active 3,5-dihydroxyhexanoic acid derivative represented by formula (8)
(wherein R 1 and R 3 are the same as above) through asymmetric hydrogenation of an optically active 3-oxo-5-hydroxyhexanoic acid derivative represented by formula (7)
(wherein R 1 and R 3 are the same as above)
DETAILED DESCRIPTION OF THE INVENTION
The present invention will now be described in detail.
In the present invention, the optically active 3-oxo-5-hydroxyhexanoic acid derivative represented by formula (2) above is subjected to asymmetric hydrogenation to produce the 3,5-dihydroxyhexanoic acid derivative represented by formula (1) above.
In particular, the compound represented by formula (3), (5), or (7) is subjected to asymmetric hydrogenation to produce the compound represented by formula (4), (6), or (8), respectively.
In formulae (1) to (8) above, R 1 represents a C 1 –C 10 alkyl group, a C 7 –C 20 aralkyl group, or a C 6 –C 20 aryl group. The alkyl, aralkyl, or aryl group may contain a substituent. The substituent may be any suitable one. For example, the substituent may be a hydroxy group, a C 1 –C 10 alkyl group, a C 1 –C 10 alkoxy group, a sulfur atom, a nitrogen atom, or an oxygen atom.
The C 1 –C 10 alkyl group may be any suitable one. For example, the C 1 –C 10 alkyl group may be methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, hexyl, or cyclohexyl. In particular, a C 1 –C 5 alkyl group is preferred.
The C 7 –C 20 aralkyl group may be any suitable one. For example, the C 7 –C 20 aralkyl may be benzyl, p-hydroxybenzyl, or p-methoxybenzyl. In particular, a C 7 –C 10 aralkyl group is preferred.
The C 6 –C 20 aryl group may be any suitable one. For example, the C 6 –C 20 aryl group may be phenyl, o-methylphenyl, m-methylphenyl, p-methylphenyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, naphthyl, anthracenyl, 2-furyl, 2-thiophenyl, 2-pyridyl, or 3-pyridyl. In particular, a C 6 –C 10 aryl group is preferred.
Preferably, R 1 is a t-butyl group.
In formulae (1), (2), (5), and (6) above, R 2 represents a C 1 –C 10 alkyl group, a C 7 –C 20 aralkyl group, or a C 6 –C 20 aryl group, each of which may contain a substituent. Examples of the alkyl, aralkyl, and aryl groups and the substituent are the same as those for R 1 described above.
In view of easy material preparation and high reaction selectivity in converting to pharmaceutical products or the like after asymmetrical hydrogenation, R 1 is preferably a group different from R 2 . As is previously noted, R 1 is preferably butyl and R 2 is preferably isopropyl.
In formulae (1), (2), (7), and (8) above, R 3 s are each independently a C 1 –C 10 alkyl group, a C 7 –C 20 aralkyl group, or a C 6 –C 20 aryl group, or together form a C 1 –C 10 alkylene group. The alkyl, aralkyl, aryl, or alkylene group may contain a substituent. Examples of the alkyl group, the aralkyl group, the aryl group, and the substituent are the same as those for R 1 described above.
Examples of two R 3 s forming a C 1 –C 10 alkylene group are not particularly limited and include ethylene, propylene, and 2,2-dimethylpropylene. In particular, C 1 –C 5 alkylene group is preferred, and ethylene or propylene is more preferred.
R 3 is preferably methyl.
In formulae (1) to (4) above, R 4 represents a C 1 –C 10 alkyl group, a C 7 –C 20 aralkyl group, or a C 6 –C 20 aryl group, each of which may contain a substituent. Examples of the alkyl group, the aralkyl group, the aryl group, and the substituent are the same as those of R 1 above.
In view of easy material preparation and reaction selectivity in converting to pharmaceutical products or the like after asymmetrical hydrogenation, R 1 is preferably a group different from R 4 . As is previously noted, R 1 is preferably butyl and R 4 is preferably phenyl.
In formulae (1) to (8) above, “*” represents an asymmetrical carbon atom.
The optically active 3-oxo-5,6-dihydroxyhexanoic acid derivative represented by formula (3) above can be produced, for example, by a method set forth in Japanese Unexamined Patent Application Publication No. 2-262537, including cyanizing a starting material, i.e., an optically active 1-chloro-2,3-propanediol and allowing the resulting product to react with a bromoacetic ester.
The optically active 4-oxo-2-hydroxyadipinic acid derivative represented by formula (5) above can be produced, for example, by a method set forth in Japanese Unexamined Patent Application Publication No. 4-69355, in which a starting material, i.e., an optically active malic acid, is reacted with malonic ester and then transesterified.
The ruthenium-optically active phosphine complex used as the catalyst of the asymmetric hydrogenation of the present invention will now be described. Examples of the ruthenium-optically active phosphine complex include a complex represented by formula (9), a complex represented by formula (10), and a complex represented by formula (11):
(wherein
represents an optically active phosphine ligand, Y represents a halogen atom, an acetoxy group, a methylallyl group, or an acetylacetonato group);
Ru(P—P)Y 2 (arene) (10)
(wherein P—P represents an optically active phosphine ligand, Y represents a halogen atom, an acetoxy group, a methylallyl group, or an acetylacetonato group, and arene represents an aromatic ligand); and
(wherein
is the same as above, and Z represents a halogen atom).
In formulae (9), (10), and (11) described above, the optically active phosphine ligand is an optically active bisphosphine. Examples thereof include optically active 2,2′-bisdiarylphosphino-1,1′-binaphthyl (“BINAP”), optically active bis(tert-butylmethylphosphino)ethane (“BisP*”), optically active 1,2-bis(trans-2,5-dialkylphosphorano)benzene (“DuPhos”), and optically active 1,2-bis(trans-2,5-dialkylphosphorano)ethane (“BPE”). Optically active 2,2′-bisdiarylphosphino-1,1′-binaphthyl is particularly preferred.
Examples of the aryl group in the optically active 2,2′-bisdiarylphosphino-1,1′-binaphthyl include phenyl, o-methylphenyl, m-methylphenyl, p-methylphenyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, naphthyl, anthracenyl, 2-furyl, 2-thiophenyl, 2-pyridyl, and 3-pyridyl. Phenyl is particularly preferred.
Examples of the alkyl groups in optically active 1,2-bis(trans-2,5-dialkylphosphorano)benzene and optically active 1,2-bis(trans-2,5-dialkylphosphorano)ethane include methyl, ethyl n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, hexyl, and cyclohexyl. Methyl is particularly preferred.
In formulae (9) and (10) above, Y represents a halogen atom, an acetoxy group, a methylallyl group, or an acetylacetonato group. The halogen atom is preferably iodine, bromine, or chlorine, and more preferably iodine.
In formula (10) above, arene represents an aromatic ligand. Examples of the aromatic ligand are not limited to, but include benzene, toluene, xylene, cumene, cymene, mesitylene, anisole, and naphthalene. Benzene, mesitylene, and cymene are particularly preferred due to the ease of preparing catalysts.
In formula (11) above, Z represents a halogen atom, such as iodine, bromine, or chlorine. In particular, chlorine is preferred.
In order to prepare the ruthenium-optically active phosphine complex represented by formula (9) above, the following methods have been known:
(1) a method in which a widely available [Ru(COD) (methylallyl) 2 ] (wherein COD represents cycloocta-1,5-diene) is mixed with optically active bisphosphine and the mixture is heated to produce a ruthenium-optically active phosphine complex containing a methylallyl group as Y in formula (9), or this complex is further reacted with a HBr solution to produce a ruthenium-optically active phosphine complex containing a bromine atom as Y in formula (9) (Tetrahedron: Asymmetry, vol. 5, p. 655 (1994)); (2) a method in which [RuCl 2 (DOC)] n is reacted with optically active bisphosphine in the presence of triethylamine, and the resulting reaction product is allowed to interact with sodium acetate to produce a ruthenium-optically active phosphine complex containing an acetoxy group as Y in formula (9), or the resulting complex is further mixed with a hydrogen halide aqueous solution to produce a ruthenium-optically active phosphine complex containing a halogen atom as Y in formula (9) (J. Am. Chem. Soc. (1986) vol. 108, p. 7117); (3) a method in which Ru(acac) 3 (wherein acac represents an acetylacetonato group) is reacted with an optically active bisphosphine to produce a ruthenium-optically active phosphine complex having an acetylacetonato group as Y in formula (9) (Organometallics (1993), vol. 12, p. 1467).
In particular, the method of paragraph (1) above is preferred.
The ruthenium-optically active phosphine complex represented by formula (10) described above can be prepared by a conventionally known method in which [RuY 2 (arene)] 2 and optically active bisphosphine are heated in dimethylformamide to produce Ru(P—P)Y 2 (arene) (J. Org. Chem. vol. 57, p. 4053 (1992)).
The ruthenium-optically active phosphine complex represented by formula (11) described above can be prepared by a conventionally known method in which [RuCl 2 (COD)] n is reacted with optically active bisphosphine in the presence of triethylamine (Organometallics (1996), vol. 15, p. 1521).
Among the complexes represented by formulae (9) to (11), the complexes represented by formulae (9) and (10) are particularly preferred as the catalyst for the asymmetric hydrogenation in the present invention since these complexes can render a high stereoselectivity and a high yield and allow hydrogenation under low hydrogen pressure. In particular, the complex represented by formula (9) is more preferred, and the RuBr 2 BINAP complex is most preferred.
The asymmetric hydrogenation process catalyzed by the ruthenium-optically active phosphine complex will now be explained.
The amount of asymmetric hydrogenation catalyst may be any suitable one as long as the reaction can be sufficiently carried out. The preferable amount of catalyst differs depending on the type of catalyst and solvent, and the conditions of hydrogenation. In view of reaction rate and cost efficiency, the equivalent of the catalyst is preferably 1/50 to 1/100,000 and more preferably 1/100 to 1/10,000 relative to the compound represented by formula (2) above.
During the reaction, the hydrogen pressure is preferably 1 to 100 kg/cm 2 , and more preferably 1 to 10 kg/cm 2 .
Examples of the reaction solvent include dichloromethane, chloroform, toluene, benzene, tetrahydrofuran, diethylether, ethyl acetate, N,N-dimethylformamide, formamide, acetone, butanol, isopropanol, ethanol, methanol, and water. These solvents can be used alone or in combination. Preferably, the reaction solvent is water, methanol, or a mixture of methanol and water. More preferably, the reaction solvent is a mixture of methanol and water.
The ratio of methanol to water in the methanol-water mixed solvent described above may be any suitable one but is preferably 100/1 to 1/1, and more preferably 20/1 to 4/1.
For example, reaction may be carried out in the above-described solvent under moderate conditions, i.e., at a reaction temperature in the range of −50° C. to 150° C. The reaction temperature is preferably 0° C. to 60° C. in order to increase the yield. The reaction time is preferably 30 minutes to 24 hours, and more preferably 30 minutes to 20 hours.
Upon completion of the reaction, the resultant reaction mixture is purified by silica gel chromatography or by recrystallization to obtain a target optically active compound.
Best Mode for Carrying out the Invention
The present invention will now be described specifically by way of examples. The present invention is in no way limited by these examples.
EXAMPLE 1
Synthesis of (2S, 4R)-2,4-dihydroxyadipinic acid 1-isopropyl 6-tert-butylester
To (S)-4-oxo-2-hydroxyadipinic acid 1-isopropyl 6-tert-butylester (137 mg, 0.50 mmol) and RuBr 2 (R)-BINAP (4.4 mg, 0.0050 mmol) (BINAP was 2,2′-bisdiphenylphosphino-1,1′-binaphthyl), 2 mL of a methanol-water (10/1) solution was added to completely dissolve the (S)-4-oxo-2-hydroxyadipinic acid 1-isopropyl 6-tert-butylester and RuBr 2 (R)-BINAP in an argon atmosphere. Hydrogen replacement at −78° C. was performed three times. After the temperature of the resulting mixture had increased to 50° C., the mixture was allowed to react for three hours under a hydrogen pressure of 5.0 kg/cm 2 . After extraction of hydrogen, the mixture was condensed and purified by silica gel column chromatography. As a result, 97.8 mg (71%) of (2S, 4R)-2,4-dihydroxyadipinic acid 1-isopropyl 6-tert-butylester was obtained. The diastereomer ratio as determined by nuclear magnetic resonance (NMR) analysis was (2S, 4R):(2S, 4S)=95.5/4.5.
1 H-NMR (400 MHz, CDCl 3 ): (2S, 4R) δ1.28 (d, J=6.4 Hz, 6H), 1.46 (s, 9H), 1.80–2.00 (m, 2H), 2.44 (d, J =6.0 Hz, 2H), 3.35 (br, 1H), 3.49 (br, 1H), 4.26–4.41 (m, 2H), 5.09 (sep, J=4.5 Hz, 1H). (2S, 4S,) δ1.28 (d, J=6.4 Hz, 6H), 1.47 (s, 9H), 1.67–1.70 (m, 1H), 1.94–2.10 (m, 1H), 2.43 (d, J=3.6 Hz, 2H), 3.22 (br, 1H), 3.46 (br, 1H), 4.20–4.30 (m, 1H), 4.35–4.50 (m, 1H), 5.11 (sep, J=6.4 Hz, 1H).
EXAMPLE 2
Synthesis of (2S, 4R)-2,4-dihydroxyadipinic acid 1-isopropyl 6-tert-butylester
To (S)-4-oxo-2-hydroxyadipinic acid 1-isopropyl 6-tert-butylester (137 mg, 0.50 mmol) and RuBr 2 (R)-BINAP (4.4 mg, 0.0050 mmol) (BINAP was 2,2′-bisdiphenylphosphino-1,1′-binaphthyl), 2 mL of a methanol-water (10/1) solution was added to completely dissolve (S)-4-oxo-2-hydroxyadipinic acid 1-isopropyl 6-tert-butylester and RuBr 2 (R)-BINAP in argon atmosphere. Hydrogen replacement at −78° C. was performed three times. After the temperature of the resulting mixture is increased to 50° C., the mixture was allowed to react for twenty hours under a hydrogen pressure of 5.0 kg/cm 2 . After extraction of hydrogen, the mixture was condensed and purified by silica gel column chromatography. As a result, 37.9 mg (28%) of (2S, 4R)-2,4-dihydroxyadipinic acid 1-isopropyl 6-tert-butylester was obtained. The diastereomer ratio reported by nuclear magnetic resonance (NMR) analysis was (2S, 4R):(2S, 4S)=94.4/5.6.
EXAMPLE 3
Synthesis of (2S, 4R)-2,4-dihydroxyadipinic acid 1-isopropyl 6-tert-butylester
To (S)-4-oxo-2-hydroxyadipinic acid 1-isopropyl 6-tert-butylester (137 mg, 0.50 mmol) and RuBr 2 BisP* (2.5 mg, 0.0050 mmol) (BisP* was (S,S)bis(tert-butylmethylphosphino)ethane), 2 mL of a methanol-water (10/1) solution was added to completely dissolve the (S)-4-oxo-2-hydroxyadipinic acid 1-isopropyl 6-tert-butylester and RuBr 2 BisP* in an argon atmosphere. Hydrogen replacement at −78° C. was performed three times. After the temperature of the resulting mixture had increased to 50° C., the mixture was allowed to react for twenty hours under a hydrogen pressure of 5.0 kg/cm 2 . After extraction of hydrogen, the mixture was condensed and purified by silica gel column chromatography. As a result, 50.8 mg (37%) of (2S, 4R)-2,4-dihydroxyadipinic acid 1-isopropyl 6-tert-butylester was obtained. The diastereomer ratio determined by nuclear magnetic resonance (NMR) analysis was (2S, 4R):(2S, 4S)=60/40.
EXAMPLE 4
Synthesis of (2S, 4S)-2,4-dihydroxyadipinic acid 1-isopropyl 6-tert-butylester
To (S)-4-oxo-2-hydroxyadipinic acid 1-isopropyl 6-tert-butylester (137 mg, 0.50 mmol) and RuBr 2 (S)-BINAP (4.4 mg, 0.0050 mmol) (BINAP was 2,2′-bisdiphenylphosphino-1,1′-binaphthyl), 2 mL of a methanol-water (10/1) solution was added to completely dissolve the (S)-4-oxo-2-hydroxyadipinic acid 1-isopropyl 6-tert-butylester and RuBr 2 (S)-BINAP in an argon atmosphere. Hydrogen replacement at −78° C. was performed three times. After the temperature of the resulting mixture had increased to 50° C., the mixture was allowed to react for twenty hours under a hydrogen pressure of 5.0 kg/cm 2 . After extraction of hydrogen, the mixture was condensed and purified by silica gel column chromatography. As a result, 46.5 mg (34%) of (2S, 4S)-2,4-dihydroxyadipinic acid 1-isopropyl 6-tert-butylester was obtained. The diastereomer ratio determined by nuclear magnetic resonance (NMR) analysis was (2S, 4R):(2S, 4S)=5.5/94.5.
EXAMPLE 5
Synthesis of (2S, 4S)-2,4-dihydroxyadipinic acid 1-isopropyl 6-tert-butylester
To (S)-4-oxo-2-hydroxyadipinic acid 1-isopropyl 6-tert-butylester (137 mg, 0.50 mmol) and RuBr 2 (S, S)-Me-DuPhos (2.5 mg, 0.0050 mmol) (Me-DuPhos was 1,2-bis(trans-2,5-dimethylphosphorano)benzene), 2 mL of a methanol-water (10/1) solution was added to completely dissolve the (S)-4-oxo-2-hydroxyadipinic acid 1-isopropyl 6-tert-butylester and RuBr 2 (S, S)-Me-DuPhos in an argon atmosphere. Hydrogen replacement at −78° C. was performed three times. After the temperature of the resulting mixture had increased to 50° C., the mixture was allowed to react for twenty hours under a hydrogen pressure of 5.0 kg/cm 2 . After extraction of hydrogen, the mixture was condensed and purified by silica gel column chromatography. As a result, 36.1 mg (26%) of (2S, 4S)-2,4-dihydroxyadipinic acid 1-isopropyl 6-tert-butylester was obtained. The diastereomer ratio determined by nuclear magnetic resonance (NMR) analysis was (2S, 4R):(2S, 4S)=13/87.
EXAMPLE 6
Synthesis of (3R, 5S)-6-benzoyloxy-3,5-dihydroxyhexanoic acid tert-butylester
To (S)-6-benzoyloxy-3-oxo-5-hydroxyhexanoic acid tert-butylester (161 mg, 0.50 mmol) and RuBr 2 (R)-BINAP (4.4 mg, 0.0050 mmol) (BINAP was 2,2′-bisdiphenylphosphino-1,1′-binaphthyl), 2 mL of a methanol-water (10/1) solution was added to completely dissolve the (S)-6-benzoyloxy-3-oxo-5-hydroxyhexanoic acid tert-butylester and RuBr 2 (R)-BINAP in an argon atmosphere. Hydrogen replacement at −78° C. was performed three times. After the temperature of the resulting mixture had increased to 50° C., the mixture was allowed to react for twenty hours under a hydrogen pressure of 5.0 kg/cm 2 . After extraction of hydrogen, the mixture was condensed and purified by silica gel column chromatography. As a result, 144.4 mg (89%) of (3R, 5S)-6-benzoyloxy-3,5-dihydroxyhexanoic acid tert-butylester was obtained. The diastereomer ratio determined by high performance liquid chromatography (HPLC) analysis was (3R, 5S):(3S, 5S)=93.5/6.5 (Chiralcel-AD, hexane/isopropanol=95/5, 1.0 mL/min, UV=210 nm. Retention time: (3R, 5S) 28.2 min, (3S, 5S) 42.9 min).
1 H-NMR (500 MHz, CDCl 3 ): (3R, 5S) δ1.47 (s, 9H), 1.68–1.78 (m, 2H), 2.44 (d, J=6.1 Hz, 2H), 3.71 (br, 1H), 3.83 (br, 1H), 4.24–4.36 (m, 4H), 7.43–7.46 (m, 2H), 7.55–7.58 (m, 1H), 8.04–8.08 (m, 2H). (3S, 5S) δ1.47 (s, 9H), 1.73 (t, J=6 Hz, 2H), 2.46 (d, J=7.0 Hz, 2H), 2.99 (br, 1H), 3.57 (br, 1H), 4.25–4.45 (m, 4H), 7.43–7.46 (m, 2H), 7.55–7.59 (m, 1H), 8.04–8.06 (m, 2H).
EXAMPLE 7
Synthesis of (3S, 5S)-6-benzoyloxy-3,5-dihydroxyhexanoic acid tert-butylester
To (S)-6-benzoyloxy-3-oxo-5-hydroxyhexanoic acid tert-butylester (161 mg, 0.50 mmol) and RuBr 2 (S)-BINAP (4.4 mg, 0.0050 mmol) (BINAP was 2,2′-bisdiphenylphosphino-1,1′-binaphthyl), 2 mL of a methanol-water (10/1) solution was added to completely dissolve the (S)-6-benzoyloxy-3-oxo-5-hydroxyhexanoic acid tert-butylester and RuBr 2 (S)-BINAP in an argon atmosphere. Hydrogen replacement at −78° C. was performed three times. After the temperature of the resulting mixture had increased to 50° C., the mixture was allowed to react for twenty hours under a hydrogen pressure of 5.0 kg/cm 2 . After extraction of hydrogen, the mixture was condensed and purified by silica gel column chromatography. As a result, 133.4 mg (82%) of (3S, 5S)-6-benzoyloxy-3,5-dihydroxyhexanoic acid tert-butylester was obtained. The diastereomer ratio determined by high performance liquid chromatography (HPLC) analysis was (3R, 5S):(3S, 5S)=10.4/89.6.
INDUSTRIAL APPLICABILITY
According to the features of the present invention described above, an optically active 3,5-dihydroxyhexanoic acid derivative (1) can be produced by efficiently and cost-effectively reducing an easily synthesizable optically active 3-oxo-5-hydroxyhexanoic acid derivative (2) through asymmetrical hydrogenation catalyzed by a ruthenium-optically active phosphine complex. | A method for producing an optically active 3,5-dihydroxyhexanoic acid derivative by stereoselectively reducing an optically active 3-oxo-5-hydroxyhexanoic acid derivative is provided. The method, which requires neither an ultralow-temperature reactor, an incubator, nor protection of the 5-position hydroxy group, is simple and economical.
An optically active 3,5-dihydroxyhexanoic acid derivative is produced by asymmetrical hydrogenation of an optically active 3-oxo-5-hydroxyhexanoic acid derivative catalyzed by an RuBr 2 BINAP complex prepared from a ruthenium complex and a ruthenium-optically active phosphine complex, i.e., 2,2′-bisdiarylphosphino-1,1′-binaphthyl (BINAP), while using extremely inexpensive hydrogen as the reductant. | 2 |
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The field of the invention pertains to organic resin-coated proppants for use in fracturing subterranean geological formations to stimulate oil and gas production.
[0003] 2. Description of the Related Art
[0004] Hydraulic fracturing, or “fracking” is a now old technique which has been used to stimulate oil and gas recovery. A fluid containing solid particles is injected into the oil- or gas-bearing (or both) formation to fracture the rock in the hydrocarbon-bearing zone. By such means, “clear” passages are created which allow the hydrocarbon and associated water, if present, to flow more rapidly to the well bore. This technique is becoming more widely used in shale formations where vertical movement through shale layers is very low.
[0005] Proppants are used in the fracturing fluid to ensure that the fractures remain open to flow. For this purpose, coarse sand and gravel have been used, as well as ceramic proppants. Unfortunately, these are somewhat brittle materials which can be crushed at the high pressures of the subterranean formations, thus reducing the fracture width as well as generating fines which can plug open spaces between remaining proppant particles.
[0006] Thus, fracture conductivity may be reduced by small proppants or fines. In fracture conductivity testing using proppants confined between sandstone cores, embedment of proppant into the core is frequently observed after exposure to elevated stress. In the process of embedment, spalling of fines from the rock is displaced into the proppant pack. Proppant pack conductivity damage from embedment results in loss of proppant pack width as the proppant embeds into the rock and proppant pack pore throats are plugged by displaced formation fines. The pack permeability is thereby reduced.
[0007] A second source of fines results from proppant crushing. Such fines are generated at the fracture-face to proppant pack interface as in situ closure stresses acting upon the fracture cause failure of the proppant, the formation rock, or both. Such stresses may cause the proppant to be compressed together such that fines are generated from the proppant pack and/or reservoir matrix. Further, fines composed of formation material (e.g., shale, sand, coal fines, etc.) may present similar problems and may be produced, for example, within the fractured formation due to stresses and forces applied to the formation during fracturing.
[0008] Proppant packs containing both sand and a deformable polymer proppants substantially reduce proppant crushing. Such proppant packs are disclosed in U.S. Pat. Nos. 6,059,034 and 6,330,916. In addition to sand, such proppant packs contain deformable additives which act as a cushion and minimize the point stresses applied to the proppant and limit crushing of the sand. However, at elevated stress levels, the permeability and porosity levels of such proppant packs are compromised by embedment and spalling. The proppants used in these references consist of a traditional proppant, i.e. sand, and a deformable particulate material such as polystyrene/divinylbenzene beads.
[0009] A further concept for improving the conductivity of proppants is to coat the proppant particles with an organic resin. In U.S. Pat. No. 3,929,191, sand or beads are coated with a fusible, i.e. thermoplastic (non-crosslinked) phenolic resin and injected into the geological formation. The phenolic resin then crosslinks in situ to an infusible state, and agglomerates of the proppants also form as a result. In the process for making such proppants, it is disclosed to employ a very minor amount of aminoalkylalkoxysilane as a coupling agent. However, the small amount of coupling agent used cannot form a silicone resin, and is used only to increase adherence of the phenolic resin to the sand particles. Phenolic resin coated proppants have been widely used, but suffer from the disadvantage that they continue to crosslink under the harsh subterranean conditions, becoming brittle. They may then fracture, generating the problems addressed previously.
[0010] In U.S. Pat. No. 7,883,740, it is proposed to coat proppant particles with a two layer coating, the first layer of a curable resin which is allowed to cure, followed by deposition of a second layer which is also allowed to cure. The two layers may be formed of the same curable resin. Such particles have the unwanted characteristic of shedding their outer layer, generating deformable fines which can substantially reduce porosity.
[0011] U.S. Pat. No. 7,322,411 discloses forming deformable proppants by coating proppant particles with a deformable polymer. Preferred polymers are phenol/formaldehyde resins, melamine/formaldehyde resins, and polyurethane resins. The formaldehyde-based resins have a tendency, as explained earlier, to continue to crosslink and ultimately become brittle. Polyester polyol-based polyurethane resins are unstable with respect to hydrolysis, and both these and the more hydrolysis-stable polyether-based polyurethanes tend to be expensive.
[0012] In U.S. published application 2003/0186820 A1, an in situ method of producing elastomer coated proppants is disclosed, wherein a silicone elastomer-forming component in liquid form is injected into the formation together with the particulate proppant, and polymerization within the formation enables the formation of a flexible and coherent mass. The varied underground conditions create problems with such an approach, and if too elastomeric, the gel-like masses can plug the formation rather than creating the desired hydrocarbon flow paths. Moreover, the curable silicone elastomer precursors are expensive.
[0013] It would be desirable to provide proppants which are deformable and whose conductivity is thus long lasting, while maintaining the benefits of the ease of production and cost-effectiveness of phenolic coated proppants.
SUMMARY OF THE INVENTION
[0014] It has now been surprisingly discovered that stable, long lasting and cost-effective proppants suitable for use in fracturing operations can be provided by coating proppant particles with a copolymer of an arylolic resin and a silicone resin containing both D and T units.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0015] The present invention thus pertains to particulate proppants coated with arylolic resin/silicone resin copolymers to form “deformable,” crush and fracture resistant, coated proppants for use in fracturing subterranean formations.
[0016] By “proppant particle” is meant a generally hard, high modulus material commonly used in proppants. Examples include sand, gravel, ground rock such as limestone, marble, dolomite, granite, etc., glass beads, ceramic particles, ceramic beads, and the like. This list is exemplary and not limiting. It is preferred that the proppant particles be of a substantially spherical shape, and in this regard, coarse sand is preferred. Glass beads and microballoons are likewise preferred. As the average particle size of the proppant particles decreases, greater preference is given to substantially spherical particles, i.e. particles with an aspect ratio of less than 2:1 (length/diameter). This is to ensure maintenance of space for hydrocarbon flow between the particles. For coarser particles, the shape is less relevant.
[0017] By “coated proppant particles” is meant proppant particles which have been coated with an arylolic resin/silicone resin copolymer.
[0018] By “deformable” it is meant that the proppant particulates of the proppant pack substantially yield upon application of a minimum threshold level to point to point stress. The in situ deformation of the proppants form multi-planar structures or networks and thus serve as a cushion to prevent grain-to-grain contact and absorb stress. Such cushioning prevents the proppant from shattering or breaking due to stress (including stress induced by stress cycling). As a result, less fines are generated and permeability and/or conductivity is maintained. Such reduction in fines generation further permits the extension of the closure stress range in which the proppant pack may be used.
[0019] By “arylolic resin” is meant the various phenol/formaldehyde condensates, melamine/formaldehyde condensates, and melamine/phenol/formaldehyde condensates and similar formaldehyde condensation polymers. Such polymers are well known and are available in the form of both high and low molecular weight varieties from a number of providers, for example Georgia Pacific and Plastics Engineering Co. In addition to phenol and melamine as formaldehyde-reactive starting materials, other phenols such as ortho- and meta-cresol can be used. Such resins are still “arylolic/formaldehyde” resins as that term is used herein, as are also the melamine/formaldehyde resins which are produced in very similar fashion and have similar properties. It is also possible that the arylolic/formaldehyde resins contain a minority of other functional groups such as epoxy groups, although this is not preferred.
[0020] The molecular weight and degree of crosslinking of the arylol-formaldehyde resins can be increased by heating, especially while removing water as an elimination product of condensation, or by reaction with a curing agent such as hexamethylenetriamine. In any case, the molecular weight and degree of crosslinking should not be so high so as to prevent efficient coating of the proppant particles. The resins may be novolac resins or resole resins. Reference may be had to A. Gerdziella et al., Phenolic Resins: Chemistry Applications, Standardization, Safety and Ecology, 2d Ed., Springer, 2000, and to W. Hesse, “Phenolic Resins” in Ullmann's Encyclopedia of Industrial Chemistry, 2002, Wiley-VCH, Weinheim.
[0021] By “silicone resin” in the context of the present invention is meant an organopolysiloxane containing D and T units, and optionally M and Q units as well. These units are defined as in Walter Noll, Chemistry and Technology of Silicones, Academic Press, 1968, page 3, as R 3 SiO 1/2 (M); R 2 SiO 2/2 ; (D); RSiO 3/2 (T) and SiO 4/2 (Q); where R is an organic radical, preferably an alkyl, alkenyl, cycloalkenyl, aryl, alkaryl, or aralkyl radical, which may optionally be substituted by non-interfering substituents such as cyano, halo, alkoxy, polyoxyalkyloxy, and the like. R may also be an alkoxy group or a silicon-based hydroxyl group, which provide for reactivity, particularly reactivity with compounds bearing hydroxyl groups, such as arylolic/formaldehyde resins. The presence of alkoxy and/or silicon-bonded hydroxyl groups is necessary in the silicone resins of the invention.
[0022] When R in the M, D, and T units are alkoxy groups —OR 1 , R 1 is a hydrocarbon group, preferably an alkyl group, and most preferably a C 1-4 alkyl group. Methyl and ethyl groups are most preferred as R 1 , and thus preferred alkoxy R groups are the methoxy and ethoxy groups.
[0023] When R is not an alkoxy group or silicon-bonded hydroxyl group, it is preferably an alkyl group containing 1-24 carbon atoms, more preferably 1 to 18 carbon atoms, and most preferably 1-4 carbon atoms. The alkyl groups may be linear, branched or on cyclic. Cyclic alkyl groups include C 5-6 cycloalkyl groups and alkyl-substituted cycloalkyl groups. Examples include the methyl, ethyl, n-propyl, 2-propyl, butyl, cyclohexyl, methylcyclohexyl, cyclohexylmethyl, octyl, isooctyl, and dodecyl radicals. Aryl groups such as phenyl or naphthyl are also preferred, as well as aralkyl groups such as the benzyl group, and alkaryl groups such as tolyl and xylyl groups. Preferred alkenyl groups include the vinyl, allyl, 2-propenyl, and 5-hexenyl radicals. Fluoroalkyl groups such as hexafluoropropyl and perfluoropropyl are useful, but are not preferred, largely due to increased cost. Preferred silicone resins, in addition to alkoxy and or Si—OH groups, contain methyl and phenyl radicals for R, preferably methyl radicals. In certain instances, R may be an aminoalkyl group. Preferred aminoalkyl groups are ω-aminoalkyl groups where the alkyl group is a C 1-6 alkyl group, and most preferred are the 3-aminopropyl group and the N-(2-aminoethyl)-3-aminopropyl group.
[0024] The silicone resins useful in the present invention include D and T units, and optionally M and Q units as well, the sum of all these units totaling 100 mol percent. The M units act as chain terminators, and preferably include trialkoxysiloxy, alkyldialkoxysilyl, and dialkylalkoxysilyl moieties. Trialkylsilyl groups are also useful, particularly when a reduction of alkoxy contact is desirable. Q units may also be present. However, when Q units are present, it is preferred that the proportion of D units increase, otherwise the resulting polymer may be too brittle for its intended use. Less than 30 mol percent of Q units, based on the sum of M, D, Q, and T units are preferably present, more preferably less than 20 mol percent, and yet more preferably less than 10 mol percent. Most preferably, less than 5 mol percent of Q units are present, especially no Q units. The T units are preferably present in amounts of 30-95 mol percent, more preferably 40-85 mol percent, and most preferably 60-85 mol percent. The D units are preferably present in amounts of 5-70 mol percent, more preferably 15-60 mol percent, and most preferably 15-40 mol percent. Higher amounts of D units relative to T units in the above ranges increases the elastomeric nature of the coated proppant, and vice versa.
[0025] The silicone resins of the invention are thus highly branched, crosslinked structures which still have elastomeric character due to the presence of the D units in the resin. Such resins are commercially available or can be made by standard methods in silicone resin chemistry, for example by cohydrolysis of the corresponding chlorosilanes or alkoxysilanes. For example, a DT resin can be prepared by condensation of D unit precursor dichlorodimethylsilane and T unit precursor trichloromethysilane. The cohydrolysis is generally conducted in aqueous acidic and alcoholic media, often in the presence of an organic solvent such as toluene, and as a result of the cohydrolysis conditions, the resulting resin will also contain silanol groups and/or alkoxy groups. The amounts of the latter groups can be adjusted by conditions of cohydrolysis and subsequent thermal treatment. A suitable method of cohydrolysis may be found in U.S. Pat. Nos. 7,737,292 and 8,076,438 which are incorporated for this purpose by reference. A useful commercial silicone resin is Silres® SY231 available from Wacker Chemicals, Adrian, Mich. A suitable hydroxy and aminoalkyl-functional silicone resin is Silres® HP 2000, and a high T-content resin is Silres® MSE 100, both available from the same source.
[0026] The reaction of the organosilicon compound with the arylolic resin may be accomplished by various procedures which are known in the art or can be accomplished by methods known in organic chemistry and organosilicon chemistry. Suitable methods are described, for example, in U.S. Pat. Nos. 5,177,157; 5,799,705, and 5,804,000, for example, which are incorporated herein by reference.
[0027] In one method, as exemplified in U.S. Pat. No. 5,177,157, the silicone portion of the copolymer is derived by first reacting a trialkoxysilane with a novolac or resole phenolic resin. The alkoxy groups are preferably used in stoichiometric excess. The resulting silane-modified phenolic resin is then hydrolyzed, creating siloxane linkages through condensation of alkoxy groups. This method is not preferred, however, as the resulting copolymer will be more highly crosslinked through condensation of alkoxysilyl groups initially bonded to the phenolic resin, and the condensation of additional unreacted silanes will provide siloxanes with a high proportion of T units and only a low proportion of D units. However, such a method is applicable when a first silane functionalization is effected with a trialkoxysilane or a mixture of trialkoxy- and dialkoxysilanes, followed, after reaction, by a suitable mixture of trialkoxy-, dialkoxy-, and optionally monoalkoxy or tetralkoxy silanes. In this case, the number of D units and T units in the siloxane portion of the copolymer can be adjusted within wide limits. The result in this case is still a phenolic resin modified with an organopolysiloxane (silicone) containing the claimed proportions of D and T units. The monofunctional monoalkoxysilanes can be added during the condensation or after the prior condensation is complete, to act as end capping or chain terminating reagents, which in the latter case can moderate the molecular weight and degree of crosslinking of the polymer, and in the former and latter cases, can render the resultant copolymer less subject to further crosslinking, e.g. after injection of the coated proppant into the geological formation. It is desirable that some residual Si—OH groups and or silicon-bonded alkoxy groups remain in the copolymer prior to coating of the proppant particles, as these facilitate firm bonding to these particles, reducing the risk of shedding of the polymer coat under harsh conditions. This process may be referred to as an in situ copolymer production process. As a variant of such a process, the silanes may also be added during preparation of the arylolic resin, i.e. to the mixture of phenol (or cresol, melamine, etc.) and formaldehyde. As a variant of this method, an initial silanization with alkoxysilane such as methyltrimethoxysilane may be followed by reaction with an Si—OH or alkoxy group-containing oligomeric or polymeric organopolysiloxane.
[0028] In order to more predictably tailor the nature of the copolymer, it is preferable that in lieu of the use of reactive silanes followed by one or more condensation steps, that a preformed silicone polymer or oligomer be prepared, which contains the desired ratios of D and T units, and when desired, also M and Q units, these polymers or oligomers having residual Si—OH or silicon-bonded alkoxy functionality. These silicones may also bear, in addition to or in lieu of Si—OH and/or silicon-bonded alkoxy groups, other condensation labile groups such as oximino groups (less preferred) or acyloxy groups such as acetoxy groups. The preparation of such silicone resins, as indicated previously, is known, and many are commercially available, in a wide range of functionalities, content of functional groups, and molecular weights.
[0029] Use of preformed silicone resins is thus preferred. The silicone resins may be bonded to the phenolic resin by an in situ method, as previously described, and as disclosed in U.S. Pat. No. 5,864,000, or may be reacted with a preformed phenolic resin, as disclosed in U.S. Pat. No. 5,864,000 and U.S. Pat. No. 5,799,705.
[0030] The amount of the silicone resin contained in the arylolic resin/silicone resin copolymer may vary within rather wide limits. At the lower end of the acceptable range, the amount is dictated by the amount of heat resistance, deformability, and freedom from in situ crosslinking (after injection into the geological formation). At the high end of incorporation, the limitations become too great a degree of deformability, i.e. too “soft” an elastomer, and cost. Phenolic resins are substantially low cost commodities, whereas silanes and silicone resins are more costly. The weight proportion of the silicone resin in the copolymer, whether produced by an in situ or other method, should preferably be between 5 weight percent and 50 weight percent, based on the total weight (calculated as solids, or “neat” polymer), more preferably between 5 weight percent and 45 weight percent, and most preferably between 5 and an integral value between 5 and 15 on the low end of incorporation, and integral values between 45 and 30 weight percent on the high end, the high end being, of course, higher than the low end. A range of 10 to 30 weight percent incorporation is particularly preferred.
[0031] The copolymer, depending upon its preparation method, may be obtained as a neat liquid, which is preferred, as a solid, as an aqueous or alcoholic dispersion, or as a solution in organic solvent. Neat liquids or solutions of liquid copolymer or solid copolymer in organic solvent are preferred. If the copolymer is a liquid after preparation, it is a curable liquid copolymer which is cured to a solid during the overall coating procedure.
[0032] Following preparation of the copolymer, the copolymer, in one of the forms identified above, is used to coat proppant particles. Any method of coating may be used, for example, but not by limitation, pan coating, fluidized bed coating, coating in mixers, spray towers, or the like. Whichever method of coating is utilized, any organic solvent is preferably removed, and the coated proppant particles are recovered in dry form or in an aqueous suspension.
[0033] The coating may be applied in one or more layers. If more than one layer is used, it is preferable that the preceding layer is not substantially cured prior to coating with the subsequent layer. In this manner, the two or more layers are chemically bonded to each other, and will resist shredding.
[0034] A preferred method of coating is to introduce the proppant particles into a rotating coater or fluidized bed, and meter the coating components into the bed. A continuous procedure for coating may thus be established. The amount of polymer coating on the proppant particles is to some extent related to the temperatures and pressures expected to be encountered in the geological formation. Shallow wells may have a temperature less than 55° C., for example, and relatively low pressure as well. Moderate pressure stress of 100 psi to 5000 psi ordinarily dictates a thicker coating, whereas higher temperatures, which may range above 100° C. and pressures which may easily reach 15,000 psi ordinarily dictate a thinner coating. Coating thickness, as reflected by weight percent of copolymer coating relative to the total weight of proppant particles plus coating, generally ranges from 0.2 to 20 weight percent, more preferably 0.2 to 10 weight percent, yet more preferably 1 to 10 weight percent, and most preferably about 2 to 8 weight percent.
[0035] Aggregates of the coated proppant particles are also useful. In this sense, an aggregate is a plurality of coated proppant particles reversibly bound together in an “aggregate.” The aggregates may regenerate individual or smaller clusters of coated proppant particles during use, for example prior to or during injection into the well bore, or within the subterranean formation due to temperature and pressure stress.
[0036] The coated proppant particles may be formed into aggregates in a conventional manner. For example, coated proppant particles may be heated to elevated temperatures at which the polymer coating softens or becomes tacky, and the coated proppant particles thus “stick together,” optionally aided by pressure. The aggregates may form as a large coherent mass which is subsequently crushed into desired aggregate sizes.
[0037] The aggregates may also be prepared from a mixture of coated proppant particles and an adhesive or softenable polymer, similar to the process described above, and then crushed if necessary. The polymers may be deformable polymers of numerous chemical categories, and may be in any form, i.e. powder, spheres, microballoons, etc. The adhesive may be water soluble or water softenable. Examples of water soluble adhesives, which will begin release of coated proppant particles shortly after contact with aqueous fluids include polyvinyl alcohols, including partially hydrolyzed polyvinyl acetates and the like, polyacrylic acid polymers and salts thereof, polyvinylpyrollidones, etc. The adhesive should not be so strong or water-insensitive that the aggregates cannot break up to form smaller clusters and/or individual coated proppant particles during use.
[0038] The copolymer coated proppant particles preferably meet the API (American Petroleum Industry) standards for sphericity and/or fines.
[0039] API RP numbers 56 and 58 describe the minimum standard for sphericity as at least 0.6 and for roundness as at least 0.6. As used herein, the terms “sphericity” and “roundness” are defined as described in the API RP's and can be determined using the procedures set forth in the API RP's.
[0040] API RP 56 also sets forth some commonly recognized proppant sizes as 6/12, 8/16, 12/20, 20/40, 30/50, 40/70, and 70/140 (all values expressed as U.S. Mesh). Similarly, API RP 58 also sets forth some commonly recognized gravel sizes as 8/16, 12/20, 16/30, 20/40, 30/50, and 40/60 (all values expressed as U.S. Mesh). The API RP's further note that a minimum percentage of particulates that should fall between designated sand sizes and that not more than 0.1 weight % of the particulates should be larger than the larger sand size and not more than a maximum percentage (1 weight % in API RP 56, and 2 weight % in API RP 58) should be smaller than the small sand size. Thus, for 20/40 proppant, no more than 0.1 weight % should be larger than 20 U.S. Mesh and no more than 1 weight % smaller than 40 U.S. Mesh.
[0041] API RP's 56 and 58 describe the minimum standard for proppant and gravel turbidity as 250 FTU or less. API RP 56 describes the minimum standard for acid solubility of proppant as no more than 2 weight % loss when tested according to API RP 56 procedures for proppant sized between 6/12 Mesh and 30/50 Mesh, U.S. Sieve Series and as no more than 3 weight % loss when tested according to API RP 56 procedures for proppant sized between 40/70 Mesh and 70/140 Mesh, U.S. Sieve Series. API RP 58 describes the minimum standard for acid solubility of gravel as no more than 1 weight % loss when tested according to API RP 58 procedures. API RP 56 describes the minimum standard for crush resistance of proppant as producing not more than the suggested maximum fines as set forth in Table 1, below, for the size being tested:
[0000]
TABLE 1
Suggested Maximum Fines for Proppant
Subjected to Crushing Strength
Mesh Size
Crushing Force
Stress on
Maximum Fines
(U.S. Sieve Series)
(lbs)
Proppant (psi)
(% by weight)
6/12
6,283
2,000
20
8/16
6,283
2,000
18
12/20
9,425
3,000
16
16/30
9,425
3,000
14
20/40
12,566
4,000
14
30/50
12,566
4,000
10
40/70
15,708
5,000
8
70/140
15,708
5,000
6
[0042] Similarly, API RP 58 describes the minimum standard for crush resistance of gravel as producing not more than the suggested maximum fines as set forth in Table 2, below, for the size being tested:
[0000]
TABLE 2
Suggested Maximum Fines for Gravel
Subjected to Crushing Strength
Stress on
Mesh Size
Crushing Force
Proppant
Maximum Fines
(U.S. Sieve Series)
(lbs)
(psi)
(% by weight)
8/16
6,283
2,000
8
12/20
6,283
2,000
4
16/30
6,283
2,000
2
20/40
6,283
2,000
2
30/50
6,283
2,000
2
40/60
6,283
2,000
2
[0043] The proppants may be tested in situ or ex situ to determine their suitability for use in various geological formations.
[0044] As is well known in the art, the short-term conductivity of a particulate used in a proppant pack can be illustrated using an American Petroleum Institute (“API”) approved simulated fracture cell, according to the general procedures specified more particularly in the “Recommended Practices for Evaluating Short-Term Proppant Pack Conductivity,” API Recommended Practice 61 (RP 61) First Edition, Oct. 1, 1989.
[0045] According to this general procedure, the simulated fracture cell uses two cores of a representative subterranean formation.
[0046] The cores are positioned in the cell to define a proppant bed size of about 7 inches (18 cm) in length, about 1.5 inches (3.8 cm) in width, and about 0.25 inches (0.6 cm) in space between the two cores. Such a cell simulates a fracture created in a subterranean formation.
[0047] The proppant bed in the API cell is initially prepacked with the particulate and any other material to be tested. The cell is pre-packed by introducing the coated particulate into the cell in a fluid suspension. The fluid used can simulate the type of fluid that can be used for introducing the particulate or coated particulate into a subterranean formation.
[0048] The API cell is fitted with a 0.3 inch (0.8 cm) diameter hole at one end to simulate a perforation. This is fitted with a screen to maintain the proppant pack in place.
[0049] According to the API procedure, the flowing medium can be water, diesel, or kerosene, or other well fluids. The flowing medium is selected to simulate well conditions. The conductivity of a proppant pack can be significant different for different types of flowing medium.
[0050] The API cell is placed in a hydraulic press to apply stress loadings to simulate the stress loadings in a fracture formed in a subterranean formation. According to the general testing procedure, the conductivity of the pack can be measured at any practical and desirable stress loadings, usually starting at about 1,000 psi.
[0051] Other factors that can impact the measured conductivity of a proppant pack include, for example, temperature, and even merely the passage of time under an applied closure stress and the other conditions. The different experience of the technician running the tests can also be a factor.
[0052] Thus, for best results, the conductivity testing should be conducted in the same way each time. Furthermore, because of the complexity of the systems being simulated, there is some natural variability from one test to the next. For example, conductivity test measurements may be expected to vary in the range of about 10% to 20% from one test to the next. Thus, it is generally preferred, although not always necessary, that the testing should be repeated at least two and more preferably at least three times and an average of the conductivity measurements be used. If a particular test out of a number of tests is shown to likely be an aberration using widely accepted statistical analysis techniques, such a result can properly be excluded from the average of the measurements. While these conductivity testing procedures do not provide absolutely consistent measurements, such testing is widely accepted in the art as being at least reasonably reliable and at least reasonably consistent for the purposes of the testing.
[0053] At a minimum, a particulate for use as a proppant should be sufficiently strong to be able to withstand substantial crushing under the stress cycles of the subterranean formation into which it is intended to be deposited. Otherwise, as the particulate begins to be crushed under the increasing stress loadings, the crushed pieces of particulate will begin to plug the pore throats between the uncrushed pieces of the particulate, which will reduce the conductivity of the proppant pack. Ultimately, the particulate would be ground to dust.
[0054] The strength of a particulate is known in the art as “crush resistance,” which can be measured according to an official API RP 56/58 procedure. Of course, certain types of particulate materials are much stronger than others. The crush resistance of a particulate is not only dependent on what the particulate is, but also on the size of the particulate. All else being equal, the smaller the particle size, the greater the crush resistance. For example, 12/20 mesh size bauxite would be expected to have a lower crush resistance, and 40/60 mesh size bauxite would be expected to have a higher crush resistance than 20/40 bauxite. Crush resistance is known to also be dependent on other factors, such as temperature and the flowing medium used in the test.
[0055] Thus, for example, a typical sand, such as 20/40 mesh Brady or Ottowa sand, is known to have a crush resistance in the range of about 2,000 psi to about 3,000 psi. On the other hand, 20/40 mesh sintered bauxite can withstand a stress loading of in the range of about 8,000 psi to about 14,000 psi without substantial crushing of the particulate. Thus, bauxite could be used as a proppant in a subterranean formation that is expected to subject the particulate proppant to higher stress loadings than sand would be able to withstand. Crush resistance ranges for bauxite are published by Carbo Ceramics, in its “Technical Information” handbook dated 1995.
EXAMPLES
[0056] Uncoated 20/40 mesh white sand proppant particles are tested with and without phenolic resin coating, and with copolymer coatings prepared by reacting a phenolic resin with various silicone resin polymers containing alkoxy groups.
Comparative Example 1
[0057] White sand of 20/40 mesh is coated with a novolac phenolic resin in an amount of about 3 weight percent based on the total weight of the coated proppant. The coated proppant is analyzed for crush force and fines generation, both as initially prepared and after oven aging at 149° C. (300° F.) for six months.
Example 2
[0058] Comparative Example 1 was repeated, but the phenolic resin was replaced with a phenolic resin modified by reaction with 20 weight percent, based on the weight of the resin, of an alkoxy-functional silicone resin available from Wacker Chemical as Silres® SY231 silicone resin.
Example 3
[0059] Comparative Example 1 was repeated, but the phenolic resin was replaced with a phenolic resin modified by reaction with 20 weight percent, based on the weight of the resin, of an aminoalkyl- and alkoxy-functional silicone resin available from Wacker Chemical as Silres® HP2000.
Example 4
[0060] Comparative Example 1 was repeated, but the phenolic resin was replaced with a phenolic resin modified by reaction with 20 weight percent, based on the weight of the resin, of an alkoxy-functional silicone resin available from Wacker Chemical as Silres® MSE 100 and with a silanol-functional silicone fluid F1006.
[0061] Compared to untreated white sand, the phenolic resin coated sand (Comparative Example 1) has superior crush force and less fines generation, but the crush force decreases upon aging and fines generation increases. Examples 2, 3, and 4 all have higher crush resistance than white sand, less fines generation, and are superior in these properties after aging, as compared to the proppant particles coated with phenolic resin only.
[0062] In the foregoing Specification, unless indicated to the contrary, any numerical value stated also includes a disclosure of greater than that amount, greater than or equal to that amount, less than that amount, or less than or equal to that amount when appropriate. Thus for example, the numeral 30 at the high end of a numerical range also includes <30 and ≦30.
[0063] While 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. | Proppant particles coated with an arylolic resin/silicone resin copolymer, wherein the silicon resin contains D units and T units, are suitable for fracturing operations in geological formations and retain their deformability over time without becoming excessively brittle. | 2 |
CROSS-REFERENCE TO CORRESPONDING APPLICATIONS
This application is a continuation-in-part of U.S. patent application Ser. No. 13/374,040 filed Dec. 8, 2011, currently pending, which, in turn, is a continuation-in-part of application Ser. No. 12/592,825 filed Dec. 3, 2009, now abandoned, which, in turn, is a continuation-in-part of application Ser. No. 12/283,472 filed Sep. 12, 2008, now issued as U.S. Pat. No. 7,892,995, which, in turn, is a continuation-in-part of application Ser. No. 12/082,576 filed Apr. 11, 2008, now abandoned.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a lithium silicate glass ceramic material and a process for fabricating that material for the manufacture of machinable blocks and subsequent fabrication of single crowns with the aid of a CAD/CAM device. The invention relates to a new version of such glass ceramic containing only lithium silicate as a main crystalline phase.
2. Background Art
There are many products available that employ lithium disilicate glass ceramic covered by several U.S. patents. Some of these patents claim a process for the preparation of shaped translucent lithium disilicate glass ceramic products from a mixture of basic components (SiO 2 , Al 2 O 3 , K 2 O, Li 2 O, plus pigments and fluorescent oxides). The thermodynamic solid-liquid equilibrium of the system consisting of lithium oxide (Li 2 O) and silicon dioxide (SiO 2 ) has been extensively studied even before that material was used as a dental ceramic (1-3, 5-6).
For those skilled in the art this experimental solid-liquid equilibrium can help explain how different glass ceramics can be obtained using the same two components when they are combined in different proportions. The same solid-liquid equilibrium shows what type of stable crystal is produced as a final product of crystallization when a specific mix composition of the two components is blended, melted, and crystallized to achieve the final product.
The crystallographic data for intermediate crystal compounds in the Li 2 O—SiO 2 system is given by the Landolt-Borntein tables (4). The following are the types of crystal compositions possible in the Li 2 O—SiO 2 system: Li 8 SiO 6 , Li 4 SiO 4 or lithium orthosilicate monoclinic and orthorhombic; Li 6 Si 2 O 7 , Li 2 SiO 3 or lithium silicate; Li 2 Si 2 O or lithium disilicate monoclinic and orthorhombic; and Li 2 Si 3 O 7 lithium trisilicate. Every crystal phase is formed based upon the initial molar ratio between the two components which can be 4, 3, 2 or 1 and any combination in between.
Thus when the silicon dioxide to lithium oxide molar ratio (SiO 2 /Li 2 O) is greater than or equal to two, meaning two moles of SiO 2 are mixed with one mole of Li 2 O, the crystallized glass ceramic product will be mainly lithium disilicate (2SiO 2 .Li 2 O). This molar ratio of two is equivalent to a molar composition of lithium oxide in the binary mixture of 33% or 67% as SiO 2 . When the same molar ratio is below 2.0, (i.e. 1.7) only lithium silicate crystals are produced (Li 2 O.SiO 2 ). The lithium oxide molar composition for a ratio of 1.7 is equivalent to 37% molar or 63% as SiO 2 . The type of resulting crystal due to the specific composition ratios gives to the glass ceramic its own distinguishable chemical and physical properties. Surprisingly, the same behavior is obtained if these two main components (silicon dioxide and lithium oxide) maintain their molar ratio below two even if they are mixed with other oxides as additives and modifiers. Such other common oxides are aluminum oxide, potassium oxide, calcium oxide, zirconium oxide and coloring oxides that are incorporated into the glass matrix and give the glass ceramic its final color and translucency.
Due to the final composition of this invention using a molar ratio of SiO 2 /Li 2 O between 1.7 to 1.9, the only phase present is lithium silicate, instead of lithium disilicate, as a main constituent of the glass ceramic as a final product. This lithium silicate (Li 2 O.SiO 2 ) in this composition is thermodynamically stable meaning that it does not suffer any change in its stoichiometric compositor through the entire process. Once it is formed the only change suffered is the increase in size of the crystals at the end of the process. That means that there is no formation of any metastable lithium metasilicate which is converted to a lithium disilicate (2SiO 2 .Li 2 O) when the molar ratio (SiO 2 /Li 2 O) of the formulation is higher or equal to 2. For example, a glass ceramic with a molar ratio of silicon dioxide to lithium oxide greater than or equal to two plus additional oxides will produce, after full crystallization a lithium disilicate glass ceramic with a melting temperature of 920° C. and a linear thermal coefficient of expansion of 10.5×10 −6 /° C. as a final product and composition. In addition, during the production of this type of glass ceramic, the cast material is subjected to at least three different heat treatments: an annealing cycle for eliminating accumulated stresses, a nucleation cycle for the formation of lithium metasilicate or unstable lithium silicate, and finally a third thermal cycle to convert the unstable lithium silicate or metasilicate into a stable lithium disilicate. This complex mechanism is clearly shown in the following US patents:
Examples of those types of glass ceramics are claimed in Barret et al in U.S. Pat. No. 4,189,325 which discloses a lithium silicate glass ceramic where the raw materials are blended, melted at 1315° C. and held for 24 hours for homogenization, fritted and crushed, melted again and cast into preheated molds. They disclose a composition of silicon dioxide to lithium oxide molar ratio of two, producing a dental ceramic composed of lithium disilicate.
U.S. Pat. No. 4,480,044 to McAlinn discloses a glass ceramic formulation where the lithium silicate glass ceramic in their intermediate process stage has a thermal expansion of 13×10 −6 /° C. and the lithium disilicate has a thermal expansion of 11.4×10 −6 /° C. They disclose a machinable lithium disilicate glass ceramic with a percentage of silicon dioxide of 79.8%.
U.S. Pat. No. 4,515,634 to Wu et at discloses a castable glass ceramic composition useful as a dental restorative material. The components are blended and melted at 1400 to 1450° C., then quenched in water, dried, milled to a powder, and melted again at 1400° C. for 4 hours. Then the melt is cast into copper molds and transferred to the annealing process. The castable glass ceramic is lithium disilicate with a silicon dioxide to lithium oxide molar ratio of two, equivalent to silicon dioxide weight composition of 65%-74.7% and lithium oxide weight composition of 14.8-16.4%.
U.S. Pat. No. 5,219,799 to Beall et at discloses a lithium disilicate glass ceramic with silicon dioxide weight composition of 65%-80% and lithium oxide compositions of 8.0-19.0%. The blended raw materials are melted at 1450° C. for 16 hours and then poured into steel molds and annealed at 450° C.
U.S. Pat. No. 5,744,208 to Beall et at describes a lithium disilicate glass ceramic with silicon dioxide weight composition of 75%-95% and lithium oxide weight composition of 3-15%. The raw materials are blended, and then melted in the range of 1450-1600° C. for about 6-10 hours. The glass is then poured into steel molds. The glass is then annealed, nucleated and crystallized to produce lithium disilicate glass ceramic in the range of 500° C. to 850° C.
U.S. Pat. No. 5,968,856 to Scheweiger et al discloses a lithium disilicate glass ceramic with compositions of silicon dioxide weight between 57%-80% and lithium oxide composition 11-19%. The components are blended and melted at 1500° C. for one hour and then quenched, dried, milled, dry pressed and sintered to form blanks. The composition requires the addition of lanthanum oxide to improve the flow properties, control the crystal growth and eliminate the strong reaction of the material with the investment material used.
U.S. Pat. No. 6,514,893 to Scheweiger et al discloses a lithium disilicate glass ceramic with silicon dioxide composition of 57%-75% weight and lithium oxide composition 13-19% weight and also containing lanthanum oxide. The components are blended and fused into granulates and comminuted to a powder. Coloring oxides are then added, and the ceramic is pressed and heat treated.
U.S. Pat. No. 6,455,451 to Brodkin et al discloses a lithium disilicate glass ceramic with silicon dioxide composition of 62%-85% weight and lithium oxide composition 8-19% weight. They disclose a method of making the lithium disilicate by melting the components at 1200 to 1600° C., followed by quenching, drying, and heat treating to form the glass ceramic, followed by comminuting to a powder, compacting and sintering to a blank and pressing to form the restoration.
U.S. Pat. No. 6,517,623 to Brodkin et al discloses a pressable lithium disilicate glass ceramic where the components are melted in the range of 1200 to 1600° C., quenched, heat treated, comminuting the glass ceramic to a powder, and then compacting the powder to a starting blank before sintering the blank or the restoration.
U.S. Pat. No. 6,606,884 to Scheweiger et al describes a lithium disilicate glass ceramic where the components are mixed and melted at 1200 to 1650° C., followed by pouring the glass into water, milling and compacting, and placing the blank in a heat treatment to sinter.
U.S. Pat. No. 6,802,894 to Brodkin et al discloses a lithium disilicate glass ceramic with a silicon dioxide weight composition of 62%-85% and lithium oxide weight composition 8-19%. The components are mixed, melted at 1200 to 1600° C., and cast. The resulting glass is annealed at a range of 300 to 600° C., followed by subjecting the glass to a heat treatment from 400 to 1100° C.
U.S. Pat. No. 6,818,753 to Petticrew discloses a lithium disilicate glass ceramic with a silicon dioxide composition of 60%-80% weight and lithium oxide composition of 8-17% weight. The components are blended, melted, quenched, heat treated, milled to a powder, dry pressed, and hot pressed into the desired restoration.
Scheweiger et al U.S. Pat. No. 7,316,740 B2 claims a lithium silicate glass ceramic with silicon dioxide weight compositions of 64 to 73% and lithium oxide weight compositions of 13 to 17%. The lithium disilicate final product is demonstrated by means of a XRD pattern (FIG. 6) and DSC phase transformation curve from lithium metasilicate to lithium disilicate (FIG. 2). The DSC diagram shows the change in energy from the stage of metasilicate to disilicate, which is only necessary if lithium disilicate is desired to be the crystal phase used as a final product.
U.S. Pat. No. 7,452,836 to Apel et al discloses a lithium silicate glass ceramic with silicon dioxide composition of 64%-75% weight and lithium oxide composition of 13-17% weight producing lithium disilicate as a final product. They also describe a glass ceramic with a molar ratio of silicon dioxide to lithium oxide of at least 2.3.
U.S. Pat. No. 7,867,930 to Apel et al shows a lithium silicate glass ceramic with silicon dioxide composition of 64%-75% weight and lithium oxide composition of 13-17% weight producing lithium disilicate as a final product.
U.S. Pat. No. 7,871,948 to Apel et al describes a lithium silicate glass ceramic with silicon dioxide composition of 64%-75% weight and lithium oxide composition of 13-17% weight, producing lithium disilicate as a final product. The glass of the starting material is subjected to an initial heat treatment to form lithium metasilicate or unstable lithium silicate and then goes through a second heat treatment to convert the lithium metasilicate to a lithium disilicate.
U.S. Pat. No. 7,867,931 to Apel et al discloses a lithium silicate glass ceramic with silicon dioxide composition of 64%-75% weight and lithium oxide composition of 13-17% weight producing lithium disilicate as the final product. They also describe a glass ceramic with a molar ratio of silicon dioxide to lithium oxide in the range of 2.3 to 2.5.
U.S. Pat. No. 8,042,358 to Schweiger et al discloses a lithium silicate glass ceramic with silicon dioxide composition of 65%-70% weight and lithium oxide composition of 14-16% weight producing lithium disilicate as the final product. In their specific process the raw materials such as carbonates, oxides and phosphates are prepared and melted in the range of 1300-1600° C. for 2 to 10 hours. They explain that in order to obtain a particularly high degree of homogeneity, the glass melt obtained may be poured into water to form glass granulates and the glass granulates obtained are melted again.
U.S. Pat. No. 7,816,291 to Schwinger et al, discloses a lithium silicate dental glass ceramic where the starting glass uses a very specific composition and a specific process to provide in the intermediate stage a glass ceramic which consists of metastable lithium metasilicate. Then after machining the metastable lithium metasilicate, it is converted by two heat treatments into a lithium disilicate glass ceramic product with outstanding mechanical properties, excellent optical properties and very good chemical stability thereby undergoing only a very limited shrinkage. The metastable phase definition is broadly accepted by those skilled in the art as a thermodynamic unstable crystalline phase of lithium metasilicate which, when heated, disappears to allow the formation of a thermodynamic stable crystal phase form such as lithium disilicate. This is only possible for the specific composition used in this and all the prior art mentioned above.
For those skilled in the art it is well understood that the lithium oxide and silicon dioxide binary system has been extensively studied and several patents for dental glass ceramics have been granted in the last few years. However all the research so far falls in a range where lithium disilicate is formed as a final product and none of the references cited above discloses a lithium silicate glass ceramic as a final product. For those skilled in the art it is evident that the type of crystal produced depends exclusively on the molar ratio of silicon dioxide to lithium oxide in the glass ceramic and not the additives or modifiers added to the mixture. This molar ratio controls the type of crystal formed in the final composition and furthermore gives its name to the final glass ceramic.
More surprisingly, in the present invention and due to our specific formulation, there is no metastable lithium metasilicate in the intermediate stage or in the stage where the material can be easily machined into the shape of dental restorations. Instead a lithium silicate crystal which is thermodynamically stable is formed, keeping its stoichiometric composition through the entire process and therefore only grown as lithium silicate during the final stage of the process. As consequence no lithium disilicate is formed in the final stage of the process.
Most of the existing patents in the dental field describe the use the same basic components. The present invention uses germanium dioxide as a fundamental part of the formula. This oxide is broadly used in glass preparation for its good optical properties. The oxide has been well studied and has positive effects compared to common silicon glasses. It has been found that the addition of germanium oxide produces a melt with low viscosity, which facilitates the castability of the process and increases the thermal expansion and the refractive index of the resulting lithium silicate glass ceramic. More importantly, the addition of germanium dioxide increases the final density of the glass resulting in higher values of flexural strength than the lithium disilicate glasses free of germanium dioxide. U.S. Patent Application Publication No. 2004/0197738 to Ban et al discloses a process to make dental frame of zirconium-yttrium sintered ceramics and they describe dental porcelain with germanium oxide as a joint component different than the zirconium yttrium oxide frame. However germanium oxide is not used as a component of the framework ceramic network. It is used only in formulation of the ceramic joint and is just a part of a series of other oxides that can be joined to the framework material.
Due to the low silicon dioxide to lithium oxide molar ratio of 1.7 of the present invention, equivalent to 37% molar of lithium oxide (63% as silicon dioxide) the ceramic has a lower melting point compared to the glass ceramic of the prior art. In addition, this new glass ceramic contains the lowest silicon dioxide weight percent compared to all of the noted prior art. Therefore, due to this specific composition of lithium oxide in the mixture, the type of resulting crystal after crystallization (lithium silicate) gives to the glass ceramic its own chemical and physical properties, which makes it completely distinguishable from the prior glass ceramics noted above. Due to this distinguishable composition, the glass ceramic of the present invention, has a lower melting temperature which can be made even lower with the addition of germanium oxide. Germanium oxide replaces silicon dioxide in the glass network, causing it to have a negative effect on the resulting melting point compared to a glass ceramic containing only silicon dioxide. Thus the processing and optimal melting temperature is in the range of 1100° C. to 1200° C. instead of 1200° C. to 1650° C. of the U.S. patents cited above and specifically compared to U.S. Pat. No. 6,514,893 to Schweiger et al. The glass ceramics mentioned in the prior art patents cannot be cast in the range of 1100° C. to 1200° C. because they are too viscous due to their high silicon dioxide content therefore the processes disclosed in prior art patents with higher melting temperatures should be used. The present process will result in a more economical production because the energy employed for melting the glass is considerably lower and there are lower energy loses by radiation compared to the Schweiger process.
In addition to having a process with lower energy consumption, another significant improvement of the inventive process is related to the mixing and reaction of the components. In all of the cited prior art patents, the mix of the components is blended and melted at 1400 to 1650° C. and then cast or quenched in water. The quenched glass powder is dried, milled, and melted again in order to improve the homogeneity and the quality of the product. Surprisingly, we found that the first melting and casting process can be avoided if we perform a calcination process on the mixture of raw materials to a temperature in the range of 700 to 800° C. without melting the components. At this stage, all the raw materials in the form of salts (such as lithium carbonate as the source of lithium oxide, calcium carbonate as the source of calcium oxide, and di-ammonium phosphate as the source of phosphorous oxide) are decomposed, eliminating gases such carbon dioxide and ammonia, producing a ceramic powder free of gases. After cooling down, the calcined mix is milled again, producing a homogeneous powder with a very small particle size. The final step is melting and casting in the range of 1100° C. to 1200° C., resulting in a homogeneity of all the components. In addition, by eliminating the gases during the calcination process, the cast glass becomes bubble free, making this a significant advantage over the processes described in the prior art
The present invention is also unique compared to those in the prior art due to its composition. The use of a low melting temperature is only possible with the inventive glass ceramic because of the low content of silicon dioxide and the high content of lithium oxide. This translates to a molar oxide ratio (SiO 2 /Li 2 O) below 2.0, (i.e., 1.7) in which only lithium silicate crystals are produced (SiO 2 —Li 2 O). In addition to the composition, we have implemented a process for our glass ceramic that produces a homogeneous product and that can be used only with our specific formulation. This process cannot be used with the other prior art glass ceramics due to the lower operating temperatures.
It is emphasized that in the present glass ceramic the silicon dioxide and lithium oxide molar ratio content (SiO 2 /Li 2 O) is less than 2, specifically the oxide molar ratio is preferably about 1.7. This is specifically equivalent to 63% molar of silicon dioxide and 37% molar of lithium oxide, and specifically equivalent in the overall formulation of about 56% weight percent of all of the glass ceramic as silicon dioxide and 16.0% weight percent as lithium oxide and the remaining 28% composed of the oxide additives and modifiers. In all of the glass ceramic, only lithium silicate (Li 2 O.SiO 2 ) crystals are produced as the final crystal phase product. During the heating process of the glass, the first crystals formed are stable lithium silicate and not metastable lithium metasilicate and such crystals remain stable through the end of the growing process. This means that there is no need for a third thermal process for producing the final crystal of lithium silicate making this an additional beneficial characteristic unique to the present invention. This new ceramic has a softening temperature of about 700 to 800° C. and a linear thermal coefficient of expansion of about 12 to 12.5×10 −6 /° C. as a final product and a composition yielding completely different chemical and physical properties compared to the prior art. This is easily demonstrated in commonly assigned U.S. patent application Ser. No. 12/1592,825, paragraph [0012], FIG. 1 showing a XRD pattern diffraction where only lithium silicate crystals are present in the final product and in paragraph [0013] thereof where the glass ceramic is shown to have a percentage linear change of 0.55% measured at 500° C. and an equivalent coefficient of thermal expansion of 11.5×10 −6 /° C.
The following is a list of non-patent references noted herein:
1. BOROM, P. et al, Strength And Microstructure In Lithium Disilicate Glass-Ceramics. The authors prepare lithium disilicate glass ceramics and measured the differences between the thermal expansion of the lithium disilicate with a value of 13×10 −6 /° C. and lithium silicate with a value of 11.4×10 −6 /° C. After the heat treatment above 800° C. the only phase present is lithium disilicate for a glass ceramic composition of 71.8% of silicon dioxide and 12.6% of lithium oxide. 2. EPPLER, A., Glass Formation And Recrystallization In The Lithium Metasilicate Region Of The System Li 2 O—Al 2 O 3 —SiO 2 J. Am. Ceram. Soc., 46, {2}, 97-101, (1963). 3. HUMMEL, F. A., Thermal Expansion Properties Of Some Lithia Minerals, J. Am. Ceram. Soc., 34{8} 235-39. (1951). 4. LANDOLT-BÖRNSTEIN (LB), Zahlenwerte und Funktionen aus Physik, Chemie, Astronomie, Geophysik und Technik. 5. S. CLAUS et al, Phase Equilibria In The Li 4 SiO 4 —Li 2 SiO 3 Region Of The Pseudobinary Li 2 O—SiO 2 , Journal of Nuclear Materials, Volume 230, Issue 1, May 1996, Pages 8-11. 6. SHERMER, HERMAN, Thermal Expansion Of Binary Alkali Silicate Glasses, Journal of Research of the National Bureau of Standards. Vol. 57, No. 2, August 1956. The author prepares lithium silicate glasses with silicon oxide and lithium oxide molar ratio below 2.0 being lithium silicate with thermal expansion between 12 and 14.77×10 −6 /° C. There is no lithium disilicate using this chemical molar composition.
SUMMARY OF THE INVENTION
The present invention relates to preparation of an improved lithium silicate glass ceramic for the manufacture of blocks for dental appliance fabrication using a CAD/CAM process and hot pressing. The lithium silicate material has a chemical composition that is different from those reported in the prior art, especially because of the use of germanium dioxide in the formulas and a low silicon dioxide content. The softening points are close to the crystallization final temperature of 800° C. indicating that the samples will support the temperature process without shape deformation.
The initial components are chemical precursors, specifically aluminum hydroxide for aluminum oxide, boric acid for boron oxide, lithium carbonate for lithium oxide, ammonium hydrogen phosphate or calcium phosphate for phosphorus pentoxide, zirconium silicate or yttrium stabilized zirconia for zirconium oxide, calcium carbonate for calcium oxide, lithium fluoride for lithium oxide and fluoride, and potassium carbonate for potassium oxide. The remaining elements are single oxide precursors of silicon, cerium, titanium, tin, erbium, vanadium, germanium, samarium, niobium, yttrium, europium, tantalum, magnesium, praseodymium, and vanadium oxides.
The components are carefully weighed and then mechanically blended using a V-cone blender for about 5 to 10 minutes. Then in order to achieve uniform particle size of the components, the mixture undergoes a ball mill process for two hours. The powder obtained is put into large alumina crucibles and undergoes calcination to 800° C. for about 4 hours. In this stage the carbonate precursors, lithium carbonate, calcium carbonate, potassium carbonate, decompose releasing carbonic gas and producing the corresponding pure oxides, lithium oxide, calcium oxide and potassium oxide, respectively. In the same process the other chemical precursors, ammonium phosphate, aluminum hydroxide and boric acid also release nitrogen gases and water, producing the corresponding pure oxides, phosphorous pentoxide, aluminum oxide and boron oxide, respectively. At this stage of calcination the original powder mix loses approximately 25% of its original weight due to the evaporation losses. Also, the first reactions between the pure oxides take place in this stage, but there is never any melting of the components and no reaction takes place with the alumina crucible. After cooling down, the blend of components undergoes ball milling again, producing a homogeneous, gas free, fine powder with a particle size below 30 microns. The calcined powder can be safely stored in plastic containers for extended periods of time without any gas release and can be used any time for the next step of the process.
In the final stage of the process, the calcined powder is melted in a platinum crucible at a temperature of 1200° C. with a holding time of about 2 hours before casting. The melt with the appropriate viscosity is cast continuously over graphite molds. Surprisingly, the glass cast is bubble free due to the prior elimination of the gases during the calcination step. This constitutes a significant advantage over the processes described in the prior art. Due to the calcination process step, there is no need for a second re-melting process for improving homogeneity. The glass cast is then subjected to an annealing step followed by an intermediate crystallization step or a full crystallization step depending on what is desired as a final product.
Due to the specific molar ratio of silicon dioxide and lithium oxide (1.7/1) used in the preferred embodiments of the present invention, the only preferred crystal structure formed is lithium silicate (SiO 2 .Li 2 O) in the intermediate or full crystallized product. Surprisingly we found that in this invention, the crystal growth process can be momentarily stopped at any temperature interval between the ranges of 350° to 800° C. and then the crystal can continue growing by heating it again to reach the optimal size at 800° C. Above 800° C. the sample starts melting and the reverse process of dissolving the crystals in the glass matrix takes place.
Thus in the present invention, the intermediate crystallization process step is easily controlled by stopping the heating process at 600° C. and cooling down to room temperature. It can then be heated again to 800° C. for achieving the full crystallized product. Thus if we take the intermediate block material of lithium silicate, after the thermal heat process from room temperature to 600° C., it can be milled to a dental restoration using conventional CAD/CAM devices and then it can be heated up again to 800° C. continuing towards maximum crystal growth and achieving the optimal physical properties. Surprisingly, the same formulation, after a thermal process from room temperature to 800° C., can be easily hot pressed in the range of 800-840° C. using conventional all ceramic dental investments and commercial press furnaces (i.e., Whip Mix Pro-Press 100). For the hot press process, the dental restoration is milled in a wax block, followed by investing the wax pattern using commercial all ceramic investments. After firing the investment, the wax is burned out, allowing the cavity of the restoration to become available to fill with the ceramic. After hot pressing, the restoration achieves the optimal physical properties.
The same formulation produces the same lithium silicate crystalline phase through all the thermal process steps and the dental restoration can be optimally achieved by using either CAD/CAM or hot press techniques. Being able to achieve this with the same formulation is a unique and advantageous characteristic compared to the prior art.
BRIEF DESCRIPTION OF THE DRAWINGS
The aforementioned objects and advantages of the present invention, as well as additional objects and advantages thereof, will be more fully understood herein after as a result of a detailed description of a preferred embodiment when taken in conjunction with the following drawings in which:
FIG. 1 shows the thermal pattern profile employed for this invention from the melting glass temperature to the formation in a one or two step process of the stable lithium silicate glass ceramic. For the one step process, the cast glass ceramic is heated from point 2 to point 4. For the two step process, the cast glass ceramic is heated from point 2 to point 3 and then after milling the dental restoration is heated again from point 3 to point 4. In the first stage of the process (2 to 3), the size of the crystals of lithium silicate are controlled to a specific size and its growing process stopped by decreasing the temperature. Then in the second step the same crystals formed in step 1 continue to growth during heating again in order to achieve the appropriate crystal size.
FIG. 2 is an XRD diffraction pattern of a sample of the invention after the intermediate crystallization step (from room temperature to 600° C.) showing the presence of lithium silicate as a main constituent phase in the glass ceramic composition;
FIG. 3 is an XRD diffraction pattern of a sample of the invention after the full crystallization step (from room temperature to 800° C.) showing the presence of lithium silicate as a main constituent phase in the glass ceramic composition. Because the molar ratio of SiO 2 /Li 2 O is between 1.7 to 1.9, the crystallized phase of the final material shows the presence of mainly lithium silicate and no lithium disilicate;
FIG. 4 is an XRD diffraction pattern of a sample of this invention after hot pressing in the interval of 800° C. to 840° C. showing the presence of lithium silicate as a main constituent phase in the glass ceramic composition. Because the molar ratio of SiO 2 /Li 2 O is between 1.7 to 1.9, the crystallized phase of the final material shows the presence of mainly lithium silicate and no lithium disilicate; and
FIG. 5 is a graphical illustration of a dilatometric measurement of a sample of the invention resulting from full crystallization. The softening temperature of the intermediate step is lower than the temperature after full crystallization This is due to the crystal growth after heating the glass in the intermediate stage from room temperature to 800° C.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The prior art materials are based on the formation of lithium disilicate materials. A principal object of the present invention is to prepare a controlled lithium silicate glass ceramic using in the formulation a specific silicon dioxide and lithium oxide molar ratio with excellent physical properties for manufacturing dental restorations. The glass material subjected to a heat treatment produces an optimal lithium silicate crystal forming a glass ceramic product with outstanding mechanical properties, excellent optical properties, a very good chemical solubility, little contraction and high flexural strength values.
The lithium silicate of the present invention preferably comprises the following components and compositions:
weight % composition
Component
minimum
maximum
SiO 2
53.0
57.0
A1 2 O 3
3.0
5.0
K 2 O
3.0
5.0
CaO
0.0
1.0
B 2 O 3
0.0
2.0
CeO 2
0.0
1.0
MgO
0.0
1.0
Fluorine
0.0
1.0
Li 2 O
14.0
17.0
ZrO 2
4.0
6.0
TiO 2
0.0
3.0
P 2 O 5
2.0
3.0
SnO
0.0
1.0
Er 2 O 3
0.0
2.0
V 2 O 5
0.0
1.0
GeO 2
0.5
8.0
Ta 2 O 5
0.0
3.0
Sm 2 O 3
1.0
6.0
Pr 2 O 3
0.0
1.0
Eu 2 O 3
0.0
2.0
Y 2 O 3
0.0
5.0
Nb 2 O 5
0.0
1.0
The invention is explained in more detail below with the following examples:
The sample preparation and its elemental oxide composition are listed in Table 1.
TABLE 1
Components % weight
Example
Example
Example
Example
Example
1
2
3
4
5
SiO 2
55.03
56.19
56.21
56.21
53.88
Al 2 O 3
4.09
4.18
4.18
4.18
3.11
K 2 O
4.42
4.52
4.52
4.52
3.44
CaO
0.94
0.96
0.96
0.96
0.00
B 2 O 3
1.58
1.61
1.61
1.61
0.00
CeO 2
0.21
0.65
0.34
0.41
0.63
MgO
0.22
0.23
0.23
0.23
0.00
Fluorine
0.49
0.50
0.50
0.50
0.00
Li 2 O
15.81
16.14
16.15
16.15
14.81
ZrO 2
4.70
4.79
4.80
4.80
4.88
TiO 2
2.40
0.80
0.80
0.80
0.63
P 2 O 5
2.52
2.58
2.58
2.58
2.94
SnO
0.22
0.07
0.13
0.12
0.00
Er 2 O 3
0.37
0.76
0.36
0.21
1.26
V 2 O 5
0.39
0.22
0.26
0.11
0.03
GeO 2
0.90
0.92
0.92
0.92
7.75
Ta 2 O 5
0.07
0.15
0.22
0.01
0.00
Sm 2 O 3
2.03
4.09
4.07
4.09
5.71
Pr 2 O 3
0.03
0.33
0.04
0.00
0.88
Eu 2 O 3
0.00
0.00
0.00
1.25
0.05
Y 2 O 3
3.13
0.11
0.61
0.36
0.00
Nb 2 O 5
0.46
0.22
0.53
0.00
0.00
TOTAL
100.00
100.00
100.00
100.00
100.00
Example 6
Example 7
Example 8
Example 9
Example 10
SiO 2
54.08
54.49
56.17
53.49
56.19
A1 2 O 3
3.12
3.86
4.18
3.98
4.18
K 2 O
3.45
4.20
4.52
4.30
4.52
CaO
0.00
0.00
0.96
0.92
0.96
B 2 O 3
0.00
0.00
1.61
1.53
1.61
CeO 2
0.95
0.64
0.00
0.20
0.62
MgO
0.00
0.00
0.23
0.22
0.23
Fluorine
0.00
0.00
0.50
0.48
0.50
Li 2 O
14.85
15.25
16.15
15.37
16.14
ZrO 2
4.89
4.88
4.80
4.56
4.79
TiO 2
0.63
0.64
0.80
0.78
0.80
P 2 O 5
2.95
2.97
2.58
2.45
2.58
SnO
0.00
0.00
0.00
0.00
0.07
Er 2 O 3
1.52
1.28
0.05
0.16
0.61
V 2 O 5
0.06
0.04
0.00
0.48
0.15
GeO 2
7.77
7.70
0.92
0.87
0.92
Ta 2 O 5
0.00
0.00
2.33
0.00
0.18
Sm 2 O 3
4.82
3.34
1.83
4.90
4.05
Pr 2 O 3
0.90
0.72
0.00
0.23
0.24
Eu 2 O 3
0.00
0.00
0.05
0.00
0.00
Y 2 O 3
0.00
0.00
2.33
4.90
0.24
Nb 2 O 5
0.00
0.00
0.00
0.18
0.45
TOTAL
100.00
100.00
100.00
100.00
100.00
A particularly preferred lithium silicate material as described in the examples 1 to 10 comprises 53 to 59 wt. % of SO 2 , 14 to 19% wt. of Li 2 O and 1 to 9% of GeO 2 , where after nucleation only lithium silicate is formed and then after complete crystal growth only lithium silicate crystals are formed.
The lithium silicate material of this invention is preferably produced by a process which comprises the following steps:
(a) A mix of the precursors of the final components of the table 1, are blended together for 10 to 30 min until a mechanical mix is obtained. (b) The mix is ball milled dry or wet using zirconia media for about 1 to 2 hours to homogenize the components and achieve almost the same particle size in all the components. (c) The sample is calcined at 800° C. for about to 4 hours in order to decompose the precursors to their primary oxides and eliminate any possibility of formation of gas after the process. (d) Ball-mill the sample of step (c) in order to produce a powder with an average particle size below 30 microns. (e) The powder of step (d) is melted in a platinum crucible at a temperature between 1100 to 1200° C. for 1 to 2 hours. It is then poured into cylindrical or rectangular graphite molds and cooled down to room temperature. (f) The glass ceramic of step (e) is then subjected to an intermediate crystal growth process at a temperature of from room temperature to 600° C. for 10 to 60 min. The growth of the lithium silicate crystals is temporarily stopped for the desired intermediate size by cooling the glass ceramic to room temperature. (g) The glass ceramic of step (f) is subjected to a single step heating cycle from room temperature to 800° C. to achieve full crystallization. (h) For use in a CAD-CAM milling device, the dental restoration is made using a block after intermediate process step (f). After milling, the restoration is heated again from 350° C. to 800° C. or to full crystallization step (g) where the optimal lithium silicate crystal growth in the glass ceramic is achieved in a single step program. (i) For an alternative hot pressing technique, the sample after [step (g)] is pressed into a dental restoration at a temperature of 800-840° C., where the optimal lithium silicate crystal growth in the glass ceramic is achieved.
Coefficient of Thermal Expansion and Softening Point
The percentage linear change vs. temperature was measured using an Orton dilatometer. The coefficient of thermal expansion at 500° C. and the softening point were calculated for all the samples. For this purpose a rectangular rod of approximately 2 inches long was cast and then subjected to the intermediate crystallization cycle at 600° C. for 40 min. After this process the rod is cut into two parts. One part is used for measuring transition temperature, softening point temperature, and coefficient of thermal expansion of that process step. The second part is fully crystallized at 800° C. for about 10 minutes and is used for measuring the same properties. It is expected that after the crystallization step, the softening temperature point increases for the samples due to the formation of larger lithium silicate crystals. Test results are displayed in Table 2.
Flexural Strength
Biaxial flexural strength tests (MPa) were performed following ISO-6872 procedures. Ten round samples were cut, ground gradually and polished to a mirror finish in the intermediate stage of step (f). The samples were then fully crystallized in a single stage program from 350° C. to 800° C. for 10 minutes. Then the biaxial flexural strength was measured. For the hot pressing technique the glass ceramic of sample of step (g) is hot pressed into round discs in the interval of 800 to 840° C. Then the discs are ground gradually and polished to a mirror finish, heated as a simulated glaze cycle, and tested. Test results expressed in MPa are displayed in Table 2.
Chemical Solubility
A chemical solubility test was performed according to ISO-6872. Ten discs samples subjected to step (g) are placed in a glass flask with an aqueous solution of 4% (V/V) of acetic acid analytical grade (Alfa Aesar). The flask is heated to a temperature of 80+/−3° C. for 16 hours. The change in weight before and after the test is determined and then the chemical solubility expressed as μg/cm 2 is calculated and shown in Table 2.
TABLE 2
Physical Properties of the Lithium silicate glass ceramic
Example
Example
Example
Example
Example
#2
#3
#4
#5
#8
Softening temperature, ° C.,
689
618
690
766
711
Intermediate stage at 600° C.
Softening temperature, ° C.
727
744
717
789
724
crystallized sample at 800° C.
Coefficient of expansion, X10 −6 /° C.
11.81
12.58
12.27
11.30
11.61
Crystallized sample at 800° C.
Flexural strength, MPa,
350+/−28
402+/−56
359+/−40
365+/−60
370+/−50
Crystallized at 800° C.
Flexural strength, MPA
393+/−48
423+/−61
533+/−39
345+/−20
397+/−57
Hot pressed sample
Chemical Solubility, μg/cm 2
72
58
65
39
58
Crystallized sample at 800° C.
TABLE 3
Quantitative analysis of the crystalline phases of Lithium Silicate
intermediate stage and fully crystallized stage with average crystal size
Quantitative Phase Analysis (wt. %)
Chemical
Lithium Silicate partially
Lithium Silicate fully
formula
crystallized at 600° C.
crystallized at 800° C.
Li 2 SiO 3
43.1%
(183Å)
54.1%
(767Å)
Li 3 PO 4
5.3%
(738Å)
Amorphous
56.9%
40.6%
The table 3 shows the quantitative analysis of the crystalline phases present in the two samples. The partially crystallized sample contains mainly Lithium silicate whereas the fully crystallized sample contains 91% as lithium silicate and 9% as lithium phosphate of the total crystalline phases present. Only two heating steps are necessary ( FIG. 1 ). For the one step process the casted glass ceramic is heated from 2 to 4 of the graph of FIG. 1 . For the two step process the casted glass ceramic is heated from 2 to 3 of the graph of FIG. 1 and then after milling the dental restoration heated again from 3 to 4. In the first stage of the process (2 to 3), the size of the crystals of lithium silicate are controlled to an average value of 183 Angstroms. At this crystal size stage the glass material can be easily milled to a dental restoration using conventional CAD/CAM devices. Then the growing process is stopped by decreasing the temperature and subsequence increase in the glass viscosity. Then in the second step the same crystals formed in step 1 continue to growth during heating again to a size averaging 770 Angstroms. Those values are calculated from the XRD patterns. The lithium silicate glass ceramic produced by this process achieves an extraordinary translucency and shade that resemble natural teeth. The total weight percentage of the crystalline phase achieved is about 60%. During these two heating steps, the mainly crystal phase present is lithium silicate and there is no lithium disilcate.
The preferred range composition (in % of this glass ceramic material is the following:
TABLE 4
Preferred Range of Composition Components
weight % composition
Component
minimum
maximum
SiO 2
53.5
56.2
A1 2 O 3
3.1
4.2
K 2 O
3.4
4.5
CaO
0.0
1.0
B 2 O 3
0.0
1.6
CeO 2
0.0
1.0
MgO
0.0
0.2
Fluorine
0.0
0.5
Li 2 O
14.8
16.1
ZrO 2
4.6
6.0
TiO 2
0.6
2.4
P 2 O 5
2.5
3.0
SnO
0.0
0.2
Er 2 O 3
0.1
1.5
V 2 O 5
0.0
0.5
GeO 2
0.9
7.8
Ta 2 O 5
0.0
2.3
Sm 2 O 3
1.8
5.7
Pr 2 O 3
0.0
0.9
Eu 2 O 3
0.0
1.3
Y 2 O 3
0.0
4.9
Nb 2 O 5
0.0
0.5
One preferred example of this material has the following specific composition:
TABLE 5
Preferred Composition
Component
Weight %
SiO 2
55.74
A1 2 O 3
4.15
K 2 O
4.48
CaO
0.95
B 2 O 3
1.60
MgO
0.23
Fluorine
0.50
Li 2 O
16.01
ZrO 2
4.76
TiO 2
0.80
P 2 O 5
2.56
GeO 2
0.91
Coloring oxides
7.32
Having thus disclosed a number of embodiments of the formulation of the present invention, including a preferred range of components, a preferred formula thereof and a preferred fabrication process, those having skill in the relevant arts will now perceive various modifications and additions. Therefore, the scope hereof is to be limited only by the appended claims and their equivalents. | A method of fabricating a one crystalline phase lithium silicate glass ceramic and the manufacture of machinable blocks for dental appliances using a CAD/CAM device. The resulting glass ceramic contains a thermodynamically stable lithium silicate crystal through each of the steps of the process due to its specific material formulation. | 0 |
BACKGROUND OF THE INVENTION
This invention relates to healing wounds.
Growth factors are polypeptide hormones which stimulate a defined population of target cells. Examples of growth factors include platelet-derived growth factor (PDGF), insulin-like growth factor (IGF-I), transforming growth factor beta (TGF-β), transforming growth factor alpha (TGF-α), epidermal growth factor (EGF), and fibroblast growth factor (FGF), and interleukin-1 (IL-1). PDGF is a cationic, heat-stable protein found in the granules of circulating platelets which is known to stimulate in vitro protein synthesis and collagen production by fibroblasts. It is also known to act as an in vitro mitogen and chemotactic agent for fibroblasts, and smooth muscle cells.
It has been proposed to use PDGF to promote in vivo wound healing. For example, Grotendorst (1984) J. Trauma 24:549-52 describes adding PDGF to Hunt-Schilling wire mesh chambers impregnated with a collagen gel and implanted in the backs of rats; PDGF was found to increase the amount of new collagen synthesized. However, Leitzel et al. (1985) J. Dermatol. Surg. Oncol. 11:617-22 were unable to accelerate normal wound healing in hamsters using PDGF alone or in combination with FGF and EGF.
Michaeli, et al. (1984) In Soft and Hard Tissue Repair (Hunt, T. K. et al., Eds), Praeger Publishers, New York, pp. 380-394, report that application of a partially purified preparation of PDGF obtained from platelet-rich plasma stimulated angiogenesis when implanted in rabbit corneas. Because PDGF is not an angiogenic growth factor the investigators suggested that an unknown factor in their partially purified PDGF preparation was responsible for the angiogenic effect. Lynch et al , Role of Platelet-Derived Growth Factor in Wound Healing: Synergistic Effects with Other Growth Factors, Proc. Natl. Acad. Sci. U.S.A., Vol. 84, 7696-7700, and Growth Factors in Wound Healing (1989), J. Clin. Invest., Vol. 84, 640-646 demonstrated that purified PDGF preparations, including recombinant PDGF 2 preparations, did not produce a significant effect on connective tissue and epithelial layer regeneration in wound healing studies. In contrast, when purified PDGF was combined with either IGF-I, IGF-II or TGF-alpha a dramatic synergistic effect was seen both in connective tissue regeneration and re epithelialization. Application of IGF-I or II or TGF-alpha alone did not produce any significant effect in connective tissue and epithelial layer regeneration.
Interleukin-1 is a growth factor (or cytokine) which is produced naturally by several cell types, including lymphocytes and macrophages (Kaplan et al , Interleukin-1 and the Response to Injury, (1989) Immunol. Res., Vol. 8, 118-129 . Purified, biologically active IL 1 has a molecular weight of about 17.5 Kd. It occurs in two forms (alpha and beta) with identical biological activity but significant differences in amino acid sequences. Here, the term "IL-1" includes both IL 1 alpha and IL 1 beta, as well as the larger precursor forms of both isoforms. IL-1 is characteristic for both neutrophils and mononuclear cells and stimulates fibroblast and keratinocyte proliferation in vitro, in tissue culture (Kaplan et al.). It is also chemoattractant for epidermal cells in vitro, in culture (Martinet et al., Identification and Characterization of Chemoattractants for Epidermal Cells, J. Invest. Dermatol., Vol. 90, 122-126, 1988) and induces changes in extracellular glycosaminoglycan composition (Bronson et al., Interleukin-1 Induced Changes in Glycosaminoglycan Composition of Cutaneous Scar-Derived Fibroblasts in Culture, Collagen Rel. Res., Vol 8, 1988, 199-208).
SUMMARY OF THE INVENTION
In general, the invention features healing an external wound in a mammal, e.g., a human patient, by applying to the wound an effective amount of a composition that includes a combination of purified PDGF and purified IL-1, or purified IGF-1 and purified IL-1. The IL 1 can be isolated from natural sources or, more preferably, produced by recombinant technology. The composition of the invention aids in healing the wound, at least in part, by promoting the growth of epithelial and connective tissue and the synthesis of total protein and collagen. Wound healing using the composition of the invention is more effective than that achieved in the absence of treatment (i.e., without applying exogenous agents) or by treatment with purified PDGF alone, purified IGF-1 alone, or purified IL-1 alone.
A preferred composition of the invention is prepared by combining, in a pharmaceutically acceptable carrier substance, e.g., commercially available inert gels, or membranes, or liquids, purified PDGF and IL-1 (both of which are commercially available). A second composition for promoting wound healing is prepared by combining purified IGF-1 and IL-1 in a pharmaceutically acceptable carrier. Most preferably purified PDGF and IL-1 or IGF-1 and IL-1 are combined in a weight-to weight ratio of between 1:25 and 25:1, preferably between 1:10 and 10:1. The purified PDGF may be obtained from human platelets or by recombinant DNA technology. Thus, by the term "PDGF" we mean both platelet-derived and recombinant materials of mammalian, preferably primate, origin; most preferably, the primate is a human, but can also be a chimpanzee or other primate. Recombinant PDGF can be recombinant heterodimer, made by inserting into cultured prokaryotic or eukaryotic cells DNA sequences encoding both subunits, and then allowing the translated subunits to be processed by the cells to form heterodimer, or DNA encoding just one of the subunits (preferably the beta or "2" chain) can be inserted into cells, which then are cultured to produce homodimeric PDGF (PDGF-1 or PDGF-2 homodimer).
The term "purified" as used herein refers to PDGF IGF-1 or IL-1 which, prior to mixing with the other, is 90% or greater, by weight, PDGF, IGF-1 or IL-1, i.e., is substantially free of other proteins, lipids, and carbohydrates with which it is naturally associated.
A purified protein preparation will generally yield a single major band on a polyacrylamide gel for each PDGF, IGF-1 or IL-1 component. Most preferably, the purified PDGF, IGF 1 or IL-1 used in a composition of the invention is pure as judged by amino-terminal amino acid sequence analysis.
The compositions of the invention provide a fast, effective method for healing external wounds of mammals, e.g., bed sores, lacerations and burns. The compositions enhance connective tissue formation compared to natural healing (i.e. no exogenous agents added) or pure PDGF, IGF-1 or IL-1 alone. Unlike pure PDGF, IGF-1, or IL-1 alone, the composition of PDGF/IL-1 or IGF-1/IL-1 promotes a significant increase in both new connective tissue and epithelial tissue; the epithelial layer obtained is thicker than that created by natural healing or by IL-1 alone, and also contains more epithelial projections connecting it to the new connective tissue, making it more firmly bound and protective.
Other features and advantages of the invention will be apparent from the following description of the preferred embodiments thereof, and from the claims.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
We now describe preferred embodiments of the invention.
External wounds, e.g., bed sores and burns, are treated, according to the invention, with PDGF/IL-1 or IGF-1/IL-1 mixtures prepared by combining pure PDGF and IL-1 or pure IGF-1 and IL-1. Natural or recombinant IL-1 is commercially available from R & D Systems, Minneapolis, Minnesota; Genzyme, Boston, Massachusetts; and Collaborative Research, Waltham, Massachusetts. Purified recombinant PDGF and purified PDGF derived from human platelets are commercially available from PDGF, Inc. (Boston, MA), Collaborative Research (Waltham, MA), Genzyme (Boston, MA) and Amgen Corp. (Thousand Oaks, CA). Purified PDGF can also be prepared as follows.
Five hundred to 1000 units of washed human platelet pellets are suspended in 1 M NaCl (2ml per platelet unit) and heated at 100° C. for 15 minutes. The supernatant is then separated by centrifugation and the precipitate extracted twice with the 1 M NaCl.
The extracts are combined and dialyzed against 0.08M NaCl-0.01M sodium phosphate buffer (pH 7.4) and mixed overnight at 4° C. with CM-Sephadex C-50 equilibrated with the buffer. The mixture is then poured into a column (5×100 cm), washed extensively with 0.08M NaCl-0.01M sodium phosphate buffer (pH 7.4), and eluted with 1M NaCl while 10 ml fractions are collected.
Active fractions are pooled and dialyzed against 0.3M NaCl-0.01M sodium phosphate buffer (pH 7.4), centrifuged, and passed at 4° C through a 2.5×25 cm column of Blue Sepharose (Pharmacia) equilibrated with 0.3M NaCl-0.01M sodium phosphate buffer (pH 7.4). The column is then washed with the buffer and partially purified PDGF eluted with a 1:1 solution of 1M NaCl and ethylene glycol.
The partially purified PDGF fractions are diluted (1:1) with 1M NaCl, dialyzed against 1M acetic acid, and lyophilized. The lyophilized samples are dissolved in 0.8M NaCl-0.01M sodium phosphate buffer (pH 7.4) and passed through a 1.2×40 cm column of CM-Sephadex C-50 equilibrated with the buffer. PDGF is then eluted with a NaCl radient (0.08 to 1M).
The active fractions are combined, dialyzed against 1M acetic acid, lyophilized, and dissolved in a small volume of 1M acetic acid 0.5 ml portions are applied to a 1.2×100 cm column of Biogel P-150 (100 to 200 mesh) equilibrated with 1M acetic acid. The PDGF is then eluted with 1M acetic acid while 2 ml fractions are collected.
Each active fraction containing 100 to 200 mg of protein is lyophilized, dissolved in 100 ml of 0.4% trifluoroacetic acid, and subjected to reverse phase high performance liquid chromatography on a phenyl Bondapak column (Waters). Elution with a linear acetonitrile gradient (0 to 60%) yields pure PDGF.
PDGF made by recombinant DNA technology can be prepared as follows.
Platelet-derived growth factor (PDGF) derived from human platelets contains two polypeptide sequences (PDGF-1 and PDGF-2 polypeptides; Antoniades, H. N. and Hunkapiller, M. (1983) Science 220:963-965). PDGF-1 is encoded by a gene localized in chromosome 7 (Betsholtz, C. et al , Nature 320:695-699), and PDGF-2 is encoded by the sis oncogene (Doolittle, R. et al. (1983) Science 221:275-277) localized in chromosome 22 (Dalla-Favera, L R. (1982) Science 218:686-688). The sis gene encodes the transforming protein of the Simian Sarcoma Virus (SSV) which is closely related to PDGF-2 polypeptide. The human cellular c-sis also encodes the PDGF 2 chain (Rao, C.D. et al. (1986) Proc Natl. Acad. Sci. USA 83:2392-2396). Because the two polypeptide chains of PDGF are coded by two different genes localized in separate chromosomes, the possibility exists that human PDGF consists of a disulfide-linked heterodimer of PDGF-1 and PDGF-2, or a mixture of the two homodimers (homodimer of PDGF-1 and homodimer of PDGF-2), or a mixture of the heterodimer and the two homodimers.
Mammalian cells in culture infected with the Simian Sarcoma Virus, which contains the gene encoding the PDGF-2 chain, were shown to synthesize the PDGF-2 polypeptide and to process it into a disulfide-linked homodimer (Robbins, K. et al. (1983) Nature 305:605-608). In addition, PDGF-2 homodimer reacts with antisera raised against human PDGF. Furthermore, the functional properties of the secreted PDGF-2 homodimer are similar to those of platelet-derived PDGF in that it stimulates DNA synthesis in cultured fibroblasts, it induces phosphorylation at the tyrosine residue of a 185 kd cell membrane protein, and it is capable of competing with human ( 125 I)-PDGF for binding to specific cell surface PDGF receptors (Owen, A. et al. (1984) Science 225:54-56). Similar properties were shown for the sis/PDGF-2 gene product derived from cultured normal human cells (for example, human arterial endothelial cells), or from human malignant cells expressing the sis/PDGF-2 gene (Antoniades, H. et al (1985) Cancer Cells 3:145-151).
The recombinant PDGF-2 homodimer (referred to as recombinant PDGF herein) is obtained by the introduction of cDNA clones of c-sis/PDGF-2 gene into mouse cells using an expression vector. The c-sis/PDGF 2 clone used for the expression was obtained from normal human cultured endothelial cells (Collins, T., et al. (1985) Nature 216:748-750).
Wound Healing
To determine the effectiveness of PDGF/IL-1 and IGF-1/IL 1 mixtures in promoting wound healing, the following experiments were performed.
Young white Yorkshire pigs (Parson's Farm, Hadley, MA) weighing between 10 and 15 kg were fasted for at least 6 hours prior to surgery and then anesthetized. Under aseptic conditions, the back and thoracic areas were clipped, shaved, and washed with mild soap and water. The area to be wounded was then disinfected with 70% alcohol.
Wounds measuring 1 cm×1.5 cm were induced at a depth of 0.7 mm using a modified Castroviejo electrokeratome (Storz, St. Louis, MO, as modified by Brownells, Inc.). The wounds resulted in complete removal of the epithelium, as well as a portion of the underlying dermis (comparable to a second degree burn injury). Individual wounds were separated by at least 15 mm of unwounded skin. Wounds receiving identical treatment were organized as a group and separated from other groups by at least 2 cm. Wounds receiving no growth factor treatment were separated from wounds receiving such treatment by at least 5 cm.
The wounds were treated directly with a single application of the following growth factors suspended in biocompatible gel: (1) 500 ng-1.0 μg pure recombinant PDGF-2 (purified by high performance liquid chromatography); (2) 500 ng-1.0 μg pure recombinant PDGF in combination with 500 ng-1.0 μg recombinant IL-1 alpha; (3) 500 ng-1.0 μg recombinant IL-1 alpha alone; (4) 500 ng-1.0 μg IL-1 alpha combined with 500 ng-1.0 μg of IGF-1; (5) 500 ng-1 μg IGF-1 alone.
Biopsy specimens were taken seven days after wounding.
Histologic Evaluation
Histologic specimens were prepared using standard paraffin impregnating and embedding techniques. Four micron sections were made and stained using filtered Harris hemotoxylin and alcoholic eosin; they were then observed under a microscope. All specimens were scored blindly by two investigators at equally distributed points throughout the sections. The widths of the epithelial and connective tissue layers were scored using a digitizing pad and drawing tube.
Results
The results from histologic evaluation indicated that wounds treated with the combination of purified recombinant PDGF and purified recombinant IL-1 had thicker connective tissue and epithelial layers, more extensive epithelial projections connecting these layers, and increased cellularity than wounds receiving no treatment, human IL 1 alone, or pure PDGF alone. Wounds treated with a combination of purified IGF-1 and purified IL-1 had thicker connective tissue layers and increased collagen fibers than wounds treated with IGF-1 alone or IL 1 alone. The total thickness of the newly synthesized wound tissue is shown in FIG. 1 and FIG. 2. The additive effects are indicated by the "open" portion of the bars and the effects above additive, i.e., synergistic effects, are indicated by the cross-hatched portion of the bars. The increase in the total thickness and cellularity of the newly synthesized tissue in wounds treated with either PDGF/IL-1 or IGF-1/IL-1 demonstrates that these treatments promote greater tissue growth and more rapid wound healing than would be predicted from the individual effects of these factors.
Other embodiments are within the following claims. | Healing an external wound of a mammal by administering to the mammal a composition containing purified platelet-derived growth factor and purified interleukin-1 or administering to the mammal a composition containing purified insulin-like growth factor and interleukin-1. | 0 |
BACKGROUND OF THE INVENTION
This invention relates generally to sensors for sensing physiological functions in a human being and, more particularly, to a clip for positioning and holding an optical sensor adjacent a finger or other body extremity.
Various non-invasive techniques have been developed for sensing physiological functions in a human medical patient. Such non-invasive techniques have the advantage of avoiding physical penetration of the skin. This substantially reduces the risks of infection, trauma and electrical shock and minimizes patient discomfort.
One well known technique for non-invasively sensing physiological functions involves passing infrared or visible light through a portion of a patient's body. By measuring the relative absorption at various wavelengths, information regarding the patient's physiological functions can be derived. Such "optical sensing" is particularly useful in pulse oximetry wherein the instantaneous relative oxygenation of a patient's arterial blood is determined by passing light through a blood-perfused portion of the patient's body (e.g., the finger) and instantaneously measuring the relative absorption at one or more selected wavelengths. Typically, one or more light sources (e.g., light emitting diodes or "LED's") are positioned on one side of the finger, and one or more optical detectors (e.g., photodiodes) are located on the opposite side. A clip device holds both the sources and detectors in their respective, proper positions.
Because it is sometimes necessary to monitor a physiological function for hours, days or even weeks at a time, much consideration must be given to the means by which optical sensing devices are attached or coupled to the patient. On the one hand, a firm means of attachment is desirable in order to ensure continual and reliable monitoring. On the other hand, a too firm means of attachment can cause considerable discomfort, particularly if long term monitoring is involved. Consideration, therefore, must be given to reliability and performance consistent with patient comfort.
Still further consideration should be given to the avoidance of infection and disease transfer. Although non-invasive monitors do not, as a rule, physically enter a patient's body or bloodstream, cleanliness is nevertheless recognized as essential in preventing the spread of disease. Although single-use, disposable devices are one well known way of ensuring sterility and avoiding disease transfer, the disposal of medical waste material is a growing problem, and the costs and waste associated with discarding complex, sophisticated devices after only a single use are becoming increasingly difficult to justify. Preferred devices are those that can be economically manufactured and easily cleaned for multiple use.
One known clip for mounting an optical sensor on a patient's finger is shown in U.S. Pat. No. 4,685,464. In such a clip, a pair of deformable pads, on which are mounted, respectively, a light source and a light detector, in turn are mounted on and adhered to the opposed faces of a rigid, hinged, clothespin-like housing. Although effective, the permanently affixed pads make effective cleaning somewhat difficult and inefficient.
SUMMARY OF THE INVENTION
The invention provides a non-invasive optical sensor comprising a hinged clothespin-like housing having a pair of opposed faces. The sensor includes a first contact pad having an optical source associated therewith and a second contact pad having an optical detector associated therewith. The optical sensor further includes releasable structure for securing the first and second optical pads to the opposed faces of the housing. The first and second contact pads, and the optical source and optical sensor associated therewith, are thereby readily separable from the housing for cleaning or replacement.
In one embodiment, the sensor includes a first detachable carrier engageable with one of the opposed faces of the housing and further includes a second detachable carder engageable with the other of the opposed faces of the housing.
In one embodiment, detents are provided in the housing for retaining the detachable carriers, and push button release mechanisms are provided for releasing the detents to disengage the carriers from the housing.
In one embodiment, the first and second contact pads are mounted, respectively, on the first and second detachable carriers.
In one embodiment, the optical source and the optical sensor are embedded, respectively, within the first and second contact pads.
In one embodiment, the first and second contact pads are shaped to conform to a patient's finger.
In one embodiment, at least one of the first and second contact pads is formed of non-deformable material.
In one embodiment, the housing and the carrier are formed of a molded rigid plastic.
In one embodiment, the contact pad formed of the non-deformable material is coated with a friction enhancing material.
In one embodiment, the housing includes a pair of housing members joined to each other for rotational movement around a pivot axis and for limited lateral movement toward or away from each other at the pivot axis so that the distance between the housing members can be varied over a limited range without changing the angular orientation of the housing member relative to each other to permit use of the housing on fingers of widely varying sizes.
It is an object of the present invention to provide a new and improved sensor for non-invasive optical sensing of physiological functions.
It is a further object of the present invention to provide an optical sensor that can be readily disassembled for easy cleaning and repair.
It is a further object of the present invention to provide a sensor that is effective in maintaining the optical sensing components in a preferred orientation relative to a patient's body while avoiding undue patient discomfort.
It is a further object of the present invention to provide an optical sensor that can be economically manufactured from molded plastic components.
BRIEF DESCRIPTION OF THE DRAWING
The features of the present invention that are believed to be novel are set forth with particularity in the appended claims. The invention, together with the further objects and advantages thereof, may best be understood by reference to the following description taken in conjunction with the accompanying drawings, wherein like reference numerals identify like elements, and wherein:
FIG. 1 is a perspective view of an optical sensor constructed in accordance with various features of the invention.
FIG. 2 is a cross-sectional view of the optical sensor shown in FIG. 1 taken along line 2--2 thereof.
FIG. 3 is a cross-sectional view of the optical sensor shown in FIG. 1 taken along line 3--3 thereof.
FIG. 4 is a perspective view of a contact pad assembly constructed in accordance with one aspect of the invention.
FIG. 5 is a cross-sectional view of the optical sensor shown in FIG. 1 taken along line 5--5 thereof.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to the figures and, in particular, to FIG. 1, an optical sensor 10 embodying various features of the invention comprises clothespin-like structure adapted to engage an extremity of a patient's body. In the illustrated embodiment, the sensing device 10 is intended for use in pulse oximetry measurements and is adapted to engage a patient's finger or toe.
The sensor 10 includes a hinged, clothespin-like housing 12 having a pair of opposed faces 14 for grasping the patient's finger 16 therebetween. The housing comprises a pair of upper and lower housing members 18, 20 joined to each other for rotational movement around a pivot axis 22. A pair of flanges 24 extending from the rear ends of the housing members 18, 20 can be squeezed together to open the opposed faces 14 and thereby admit the patient's finger 16. A torsion spring 26 coupled to the housing members 18, 20 biases the opposed faces 14 toward each other to help retain the optical sensor 10 in place on the patient's finger 16.
In accordance with one aspect of the invention, the housing members 18, 20 are joined to each other not only for rotational movement around the pivot axis 22 but also for limited lateral movement toward or away from each other at the pivot axis 22 so that the distance between the housing members 18, 20 can be varied over a limited range without substantially changing the angular orientation of the housing members 18, 20 relative to each other. This helps keep the opposed faces 14 of the housing members 18, 20 more or less parallel to each other regardless of whether the patient's finger 16 is relatively thick or thin.
The optical sensor 10 further includes a first contact pad assembly 28 having an optical source 30 associated therewith and a second contact pad assembly 32 having an optical detector 34 associated therewith. The first contact pad assembly 28 is mounted on the upper housing member 18 and the second contact pad assembly 32 is mounted on the lower housing member 20 opposite the first contact pad assembly 28. The optical source 30 and the optical detector 34 are located so as to be opposed to each other.
In accordance with another aspect of the invention, and to facilitate cleaning or repair of the optical sensor 10, means are provided for releasably securing the first and second contact pad assemblies 28, 32 to the opposed faces of the housing 12. In the illustrated embodiment, the first and second contact pads 36, 38 are mounted on respective first and second detachable carders 40, 42 engageable with the housing members 18, 20. As best seen in FIG. 3, the interiors of the upper and lower housing members 18, 20 are provided with respective pairs of opposed, parallel slots 44, 45 that slideably receive the outer side edges of the carders 40, 42. Detents are provided for securing the carders 40, 42 within the upper and lower housing members 18, 20 when the carders 40, 42 are fully received therein. In the illustrated embodiment, a displaceable tab or hook 46 at the forward end of each carrier 40, 42 engages a complementary tab 48 in the housing member 18, 20. User-depressable means are provided for selectively disengaging the detents securing the first and second carders 40, 42. In the illustrated embodiment, inwardly depressable tabs 50 are formed in the first and second housing members 18, 20 immediately forwardly of the pivot axis 22. In the illustrated embodiment, each depressable tab 50 is defined by a U-shaped slot formed in each of the upper and lower housing members 18, 20. The forward end of each tab 50 includes an inwardly extending portion that, when the tab is depressed, engages the forward end of the hook 46 to disengage it from the tab 48 and thereby permit withdrawal of the carders 40, 42.
As previously noted, the first and second contact pad assemblies 28, 32, and the optical source 30 and optical detector 34 associated therewith, can be removed from the housing 12 to facilitate cleaning and/or repair or replacement of the pads or the housing. As best seen in FIG. 4, an electrical cable 52 that interconnects the optical sensor 10 with an electronic monitoring device is coupled to the optical source 30 of the first contact pad assembly 20 and a second electrical cable 54 interconnects the first electrical cable 52 with the optical detector 34 of the second contact pad assembly 38. Accordingly, the first and second cables 52, 54 and the first and second contact pad assemblies 28, 32, along with the optical source 30 and optical detector 34 associated therewith, can be handled as a single unit when it is removed from the housing 12. To remove the contact pad assemblies from the housing, the depressable tabs 50 of the upper and lower housing members 18, 20 are squeezed inwardly between the fingers while the first and second contact pad assemblies 28, 32 are pulled from the housing 12. To install the contact pad assemblies 28, 32, the assemblies are inserted into their respective housings 18, 20 making sure that the side edges of the carriers 40, 42 are received within their respective slots 44, 45. The pad assemblies are pressed inwardly until the detent hooks 46 engage their respective tabs 48. Preferably, the forward edges of the detent hooks 46 are beveled as shown to deflect the hooks 46 into place as the contact pad assemblies 28, 32 are inserted.
Preferably, the contact pads 36, 38 conform generally to the shape of the finger 16 as shown. The housing members 18, 20 and the carriers 40, 42 are preferably formed of a rigid, durable, injection molded plastic such as acrylonitrile butadiene styrene (ABS) or ABS/polycarbonate. One of the contact pads, e.g., the upper contact pad 36 can be formed of silicone rubber and can be made hollow to enable it to conform to the finger more readily. The opposite contact pad 38 is preferably formed of a rigid, durable, non-deformable plastic such as ABS or rigid PVC, and is preferably of solid construction. To avoid slippage and improve patient feel, a friction enhancing material can be applied. For example, a thin layer of silicone rubber, preferably bless than 0.015 inches thick, can be included on the upper face of the rigid, non-deformable pad 38. Alternatively, the rigid pad 38 can be highly polished to enhance friction. The optical source 30 and the optical detector 34 are each preferably embedded within their respective contact pads 36, 38. The contact pads 36, 38 are preferably securely adhered to the respective carriers 40, 42 by a suitable adhesive, such as a solvent welding agent (e.g., methylene chloride) or room temperature vulcanizing silicone rubber with an appropriate primer.
As best seen in FIGS. 2 and 5, the limited lateral movement permitted between the joined housing members 18, 20 is provided by means of a pin and slot arrangement included in the upper and lower housings 18, 20. Referring to FIG. 5, the lower housing member 20 includes, at each side, an upwardly projecting tab 56 having an outwardly projecting pin 58 formed thereon. The upper housing member 18 includes, at each side, a downwardly projecting tab 60 having an elongated slot 62 (FIG. 2) formed therein. The pin 58 of the lower housing member 20 is received within the slot 62 of the upper housing member 18 and generally provides for pivoting movement between the housing members 18, 20. Ordinarily, and as seen in FIG. 5, the bias of the torsion spring 26 pulls the pin 58 toward the upper end of the slot 62 thereby minimizing the distance between the upper and lower housing members 18, 20. When the sensor 10 is in place on the finger 16, the pin 58 can move toward the lower end of the slot 62 as needed to maintain the desired orientation of the sensor 10 on the finger 16.
Preferably, the contact pad assemblies 28, 32 and housing members 15, 20 are keyed so that the upper contact assembly 28, for example, will not fit in the lower housing member 20. This prevents improper installation of the pad assemblies and assures proper assembly of the optical sensor. In the illustrated embodiment, the width of the carders 40, 42 and their respective slots 44, 45 are different so as to prevent installation of the upper assembly 28 into the lower housing member 20 or the lower assembly 32 into the upper housing member 18.
While a particular embodiment of the invention has been shown and described, it will be obvious to those skilled in the art that changes and modifications may be made without departing from the invention in its broader aspects, and, therefore, the aim in the appended claims is to cover all such changes and modifications as fall within the true spirit and scope of the invention. | An optical sensor, for positioning and holding an optical source and optical detector on opposite sides of a patient's finger or other extremity includes a clothespin-like housing having opposed housing members. The optical source and optical detector are embedded, respectively, in separate, opposed contact pads. The contact pads are mounted on the opposed housing members. A detent mechanism and a carrier associated with each of the housing members and contact pads allows the contact pads to be detached from the housing for cleaning or repair. A pivot mechanism that permits limited lateral as well as rotational movement of the housing members relative to each other allows the sensor to accommodate fingers of varying sizes. | 0 |
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This is a divisional patent application which claims priority from U.S. patent application Ser. No. 10/402,678 filed on Mar. 27, 2003, which is a divisional of U.S. patent application Ser. No. 09/287,513 filed Apr. 7, 1999 (now U.S. Pat. No. 6,565,554), the full disclosures of which are incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] The present invention is generally related to improved robotic devices and methods, particularly for telesurgery.
[0003] Minimally invasive medical techniques are aimed at reducing the amount of extraneous tissue which is damaged during diagnostic or surgical procedures, thereby reducing patient recovery time, discomfort, and deleterious side effects. Many surgeries are performed each year in the United States. A significant amount of these surgeries can potentially be performed in a minimally invasive manner. However, only a relatively small percentage of surgeries currently use these techniques due to limitations in minimally invasive surgical instruments and techniques and the additional surgical training required to master them.
[0004] Advances in minimally invasive surgical technology could dramatically increase the number of surgeries performed in a minimally invasive manner. The average length of a hospital stay for a standard surgery is significantly longer than the average length for the equivalent surgery performed in a minimally invasive surgical manner. Thus, the complete adoption of minimally invasive techniques could save millions of hospital days, and consequently millions of dollars annually in hospital residency costs alone. Patient recovery times, patient discomfort, surgical side effects, and time away from work are also reduced with minimally invasive surgery.
[0005] The most common form of minimally invasive surgery is endoscopy. Probably the most common form of endoscopy is laparoscopy which is minimally invasive inspection and surgery inside the abdominal cavity. In standard laparoscopic surgery, a patient's abdomen is insufflated with gas, and cannula sleeves are passed through small (approximately ½ inch) incisions to provide entry ports for laparoscopic surgical instruments.
[0006] The laparoscopic surgical instruments generally include a laparoscope for viewing the surgical field, and working tools defining end effectors. Typical surgical end effectors include clamps, graspers, scissors, staplers, and needle holders, for example. The working tools are similar to those used in conventional (open) surgery, except that the working end or end effector of each tool is separated from its handle by, e.g., an approximately 12-inch long, extension tube.
[0007] To perform surgical procedures, the surgeon passes these working tools or instruments through the cannula sleeves to a required internal surgical site and manipulates them from outside the abdomen by sliding them in and out through the cannula sleeves, rotating them in the cannula sleeves, levering (i.e., pivoting) the instruments against the abdominal wall and actuating end effectors on the distal ends of the instruments from outside the abdomen. The instruments pivot around centers defined by the incisions which extend through muscles of the abdominal wall. The surgeon monitors the procedure by means of a television monitor which displays an image of the surgical site via a laparoscopic camera. The laparoscopic camera is also introduced through the abdominal wall and into the surgical site. Similar endoscopic techniques are employed in, e.g., arthroscopy, retroperitoneoscopy, pelviscopy, nephroscopy, cystoscopy, cisternoscopy, sinoscopy, hysteroscopy, urethroscopy, and the like.
[0008] There are many disadvantages relating to current minimally invasive surgical (MIS) technology. For example, existing MIS instruments deny the surgeon the flexibility of tool placement found in open surgery. Most current laparoscopic tools have rigid shafts and difficulty is experienced in approaching the worksite through the small incision. Additionally, the length and construction of many endoscopic instruments reduces the surgeon's ability to feel forces exerted by tissues and organs on the end effector of the associated tool. The lack of dexterity and sensitivity of endoscopic tools is a major impediment to the expansion of minimally invasive surgery.
[0009] Minimally invasive telesurgical systems for use in surgery are being developed to increase a surgeon's dexterity as well as to allow a surgeon to operate on a patient from a remote location. Telesurgery is a general term for surgical systems where the surgeon uses some form of remote control, e.g., a servomechanism or the like, to manipulate surgical instrument movements rather than directly holding and moving the tools by hand. In such a telesurgery system, the surgeon is typically provided with an image of the surgical site at the remote location. While viewing typically a three-dimensional image of the surgical site on a suitable viewer or display, the surgeon performs the surgical procedures on the patient by manipulating master control devices at the remote location, which control the motion of servomechanically operated instruments.
[0010] The servomechanism used for telesurgery will often accept input from two master controllers (one for each of the surgeon's hands), and may include two robotic arms. Operative communication between master control and an associated arm and instrument is achieved through a control system. The control system typically includes at least one processor which relays input commands from a master controller to an associated arm and instrument and from the arm and instrument assembly to the associated master controller in the case of, e.g., force feedback.
[0011] One objective of the present invention is to provide improved surgical techniques. Another objective is to provide improved robotic devices, systems, and methods. More specifically, it is an object of this invention to provide a method of compensating for friction in a minimally invasive surgical apparatus. It is a further object of the invention to provide a control system incorporating such a method of compensating for friction.
BRIEF SUMMARY OF THE INVENTION
[0012] The present invention provides improved devices, systems, and methods for compensating for friction within powered automatic systems, particularly for telesurgery and other telepresence applications. The invention allows uninhibited manipulation of complex linkages, enhancing the precision and dexterity with which jointed structures can be moved. This enhanced precision is particularly advantageous when applied to the robotic surgical systems now being developed. The friction compensation systems of the present invention address static friction (typically by applying a continuous load in the direction of movement of a joint) and the often more problematic static friction (generally by applying alternating loads in positive and negative joint actuation directions). The invention can accommodate imprecise velocity measurements by applying an oscillating load whenever the joint velocity reading falls within a low velocity range. Preferably, the oscillating load is insufficient to move the joint without additional input, and significantly reduces the break away input required to initiate movement. In the exemplary embodiment, a duty cycle of the oscillating load varies, favoring the apparent direction of movement of a velocity reading. The amplitude of the duty cycle may also vary, typically increasing as the velocity reading approaches zero.
[0013] In a first aspect, the invention provides a method of compensating for friction in an apparatus. The apparatus has at least one component that is selectively moveable in a positive component direction, and in a negative component direction. An actuator is operatively connected to the component. The method includes obtaining a component velocity reading, and defining a velocity reading region extending between a selected negative velocity reading and a selected positive velocity reading. A duty cycle is generated so that the duty cycle has a distribution between a positive duty cycle magnitude (corresponding to a friction compensation force in the positive component direction) and a negative duty cycle magnitude (corresponding to a friction compensation force in the negative component direction). The distribution is determined by the component velocity reading when it is within the velocity reading region. The actuator is loaded with a load defined by the duty cycle signal.
[0014] Preferably, the duty cycle signal will have a continuous positive duty cycle magnitude (which corresponds to the friction compensation force in the positive direction) when the component velocity reading is greater than the selected positive velocity reading. Similarly, the duty cycle signal will have a continuous negative duty cycle magnitude (corresponding to the friction compensation force in the negative component direction) when the component velocity reading is less than the selected negative velocity reading.
[0015] In the exemplary embodiment, the distribution of the duty cycle between the positive and negative magnitudes is proportional to the component velocity reading positioned within the velocity reading region. The positive and negative duty cycle magnitudes may take a gravity compensation model into account. Such a gravity compensation model may determine a variable gravity compensation force to applied to the component, for example, to artificially balance an unbalanced linkage system. Such a gravity compensated system may further benefit from a determination of a frictional compensation force corresponding to the gravity compensation force in both the positive and negative directions. In other words, in addition to compensating for friction, the method of the present invention may accommodate compensation factors for both friction and gravity, thereby simulating or approximating a friction-free balanced system, significantly enhancing the dexterity of movement which can be accommodated.
[0016] The selection of an appropriate oscillating frequency can significantly enhance friction compensation provided by these methods and systems. Hence, the frequency will preferably be selected so as to be sufficiently slow to enable the actuator (often including an electrical motor and a transmission system such as gears, cables, or the like) to respond to the directing duty cycle signal by applying the desired load, and sufficiently rapid so that the load cannot actually be felt, for example, by physically moving the joint and varying a position of an input master control device held by a surgeon. In other words, the frequency is preferably greater than the mechanical time constraints of the system, yet less than the electrical time constants of an electrical motor used as an actuator. Preferred duty cycle frequency ranges of the exemplary telesurgical system described herein are in a range from about 40 Hz to about 70 Hz, preferably being in a range from about 50 Hz to about 60 Hz. Application of these oscillating loads can facilitate movement of a joint in either a positive or negative direction, particularly when the velocity reading is so low that the system cannot accurately determine whether the system is at rest, moving slowing in a positive direction, or moving slowly in a negative direction. Once velocity measurement readings are high enough (a given measurement reading accuracies) in a positive or negative direction, a continuous (though not necessarily constant) force in the desired direction can overcome the dynamic friction of the joint.
[0017] In yet another aspect, the invention provides a method comprising manipulating an input device of a robotic system with a hand of an operator. An end effector is moved in sympathy with the manipulating step using a servomechanism of the robotic system. A velocity reading is obtained from a joint of the robotic system. An oscillating friction compensation load is applied on the joint when the velocity reading is within a first reading range.
[0018] Preferably, a continuous friction compensation load is applied when the reading is within a second reading range, typically above (either in the positive or negative direction) a minimum value. The continuous load can compensate for friction of the joint, and may vary so as to compensate for gravity when an orientation of the joint changes. The oscillating load similarly compensates for static friction of the joint in the positive and negative directions, at varying points along the load oscillation duty cycle. This method is particularly advantageous for compensating for friction and/or gravity in a joint of the input device for the robotic system, particularly where the oscillating load is less than a static friction of the joint so that the end effector can remain stationary in the hand of the operator.
[0019] In another aspect, the invention provides a telesurgery method comprising directing a surgical procedure by moving an input device of a telesurgery system with a hand of an operator. Tissue is manipulated by moving a surgical end effector in sympathy with the input device using a servomechanism of the telesurgery system. Static friction is compensated for in at least one joint of the robotic system by applying an oscillating load to the at least one joint when an absolute value of a velocity reading from the at least one joint is less than a velocity reading error range.
[0020] While the friction compensated joint may support the surgical end effector, it will preferably support the input device. The oscillating load is generally effected by applying a duty cycle to an actuator, and preferably by altering the duty cycle in response to the velocity reading so as to facilitate movement of the joint towards the positive orientation when the velocity reading is positive, and toward the negative orientation when the velocity reading is negative.
[0021] In yet another aspect, the invention provides a telepresence system comprising a master including an input device supported by a driven joint. A slave includes an end effector supported by a driven joint. A controller couples the master to the slave. The controller directs the end effector to move in sympathy with the input device. A sensor operatively associated with at least one of the driven joints generates a velocity reading. An actuator drivingly engages the at least one driven joint. The actuator applies an oscillating load on the joint to compensate for static friction of the joint when the velocity reading is within a low velocity range.
[0022] Preferably, the oscillating load is insufficient to move the at least one driven joint when the master remains stationary. In the exemplary embodiment, the end effector comprises a surgical end effector, and the slave is adapted to manipulate the surgical end effector within an internal surgical site through a minimally invasive surgical access.
BRIEF DESCRIPTION OF THE DRAWINGS
[0023] The invention will now be described, by way of example, and with reference to the accompanying diagrammatic drawings, in which:
[0024] FIG. 1A shows a three-dimensional view of a control station of a telesurgical system in accordance with the invention;
[0025] FIG. 1B shows a three-dimensional view of a cart or trolley of the telesurgical system, the cart carrying three robotically controlled arms, the movement of the arms being remotely controllable from the control station shown in FIG. 1A ;
[0026] FIG. 2A shows a side view of a robotic arm and surgical instrument assembly;
[0027] FIG. 2B shows a three-dimensional view corresponding to FIG. 2A ;
[0028] FIG. 3 shows a three-dimensional view of a surgical instrument;
[0029] FIG. 4 shows a schematic kinematic diagram corresponding to the side view of the robotic arm shown in FIG. 2A , and indicates the arm having been displaced from one position into another position;
[0030] FIG. 5 shows, at an enlarged scale, a wrist member and end effector of the surgical instrument shown in FIG. 3 , the wrist member and end effector being movably mounted on a working end of a shaft of the surgical instrument;
[0031] FIG. 6A shows a three-dimensional view of a hand-held part or wrist gimbal of a master control device of the telesurgical system;
[0032] FIG. 6B shows a three-dimensional view of an articulated arm portion of the master control device on which the hand-held part of FIG. 6A is mounted in use;
[0033] FIG. 6C shows a three-dimensional view of the master control device, the wrist gimbal of FIG. 6A shown in a mounted condition on the articulated arm portion of FIG. 6B ;
[0034] FIG. 7 shows a schematic three-dimensional drawing indicating the positions of the end effectors relative to a viewing end of an endoscope and the corresponding positions of master control input devices relative to the eyes of an operator, typically a surgeon;
[0035] FIG. 8 shows a schematic graphical relationship between measured velocity (v) and a required force (f) to compensate for friction;
[0036] FIG. 9 shows the graphical relationship shown in FIG. 8 and one method of compensating for friction represented in dashed lines superimposed thereon;
[0037] FIG. 10 shows the graphical relationship shown in FIG. 8 and another method of compensating for friction represented in dashed lines superimposed thereon;
[0038] FIG. 11 shows the graphical relationship shown in FIG. 8 and further indicates detail used to exemplify a method of compensating for friction in accordance with the invention superimposed thereon;
[0039] FIGS. 12 to 16 show different duty cycle distributions determined by values derived from velocity measurements indicated in FIG. 11 ;
[0040] FIG. 17 shows an algorithm representing an overview of the method of compensating for friction in accordance with the invention;
[0041] FIG. 18 shows further detail of the algorithm shown in FIG. 17 relating to gravity compensation;
[0042] FIG. 19 shows as an alternative to FIG. 18 , further detail of the algorithm shown in FIG. 17 relating to Coulomb friction compensation; and
[0043] FIG. 20 shows a schematic diagram exemplifying a required gravity compensating force on a master control and how the gravity compensating force and consequently also frictional force, varies depending on master control position.
DETAILED DESCRIPTION OF THE INVENTION
[0044] This application is related to the following patents and patent applications, the full disclosures of which are incorporated herein by reference: PCT International Application No. PCT/US98/19508, entitled “Robotic Apparatus”, filed on Sep. 18, 1998; U.S. Application Ser. No. 60/111,713, entitled “Surgical Robotic Tools, Data Architecture, and Use”, filed on Dec. 8, 1998; U.S. Application Ser. No. 60/111,711, entitled “Image Shifting for a Telerobotic System”, filed on Dec. 8, 1998; U.S. Application Ser. No. 60/111,714, entitled “Stereo Viewer System for Use in Telerobotic System”, filed on Dec. 8, 1998; U.S. Application Ser. No. 60/111,710, entitled “Master Having Redundant Degrees of Freedom”, filed Dec. 8, 1998; and U.S. Pat. No. 5,808,665, entitled “Endoscopic Surgical Instrument and Method for Use”, issued on Sep. 15, 1998; the full disclosures of which are incorporated herein by reference.
[0045] It is to be appreciated that although the method and control system of the invention is described with reference to a minimally invasive surgical apparatus in this specification, the application of the invention is not to be limited to this apparatus only, but can be used in any type of apparatus requiring friction compensation. Thus, the invention may find application in the fields of satellite dish tracking, handling hazardous substances, to name but two of many possible qualifying fields in which precisional movement is required. In some cases, it may be required to compensate for friction on a single part of a system such as on a master controller only.
[0046] Referring to FIG. 1A of the drawings, a control station of a minimally invasive telesurgical system is generally indicated by reference numeral 200 . The control station 200 includes a viewer 202 where an image of a surgical site is displayed in use. A support 204 is provided on which an operator, typically a surgeon, can rest his forearms while gripping two master controls (not shown in FIG. 1A ), one in each hand. The master controls are positioned in a space 206 inwardly beyond the support 204 . When using the control station 200 , the surgeon typically sits in a chair in front of the control station 200 , positions his eyes in front of the viewer 202 and grips the master controls one in each hand while resting his forearms on the support 204 .
[0047] In FIG. 1B of the drawings, a cart or trolley of the telesurgical system is generally indicated by reference numeral 300 . In use, the cart 300 is positioned close to a patient requiring surgery and is then normally caused to remain stationary until a surgical procedure to be performed has been completed. The cart 300 typically has wheels or castors to render it mobile. The control station 200 is typically positioned remote from the cart 300 and can be separated from the cart 300 by a great distance, even miles away.
[0048] Cart 300 typically carries three robotic arm assemblies. One of the robotic arm assemblies, indicated by reference numeral 302 , is arranged to hold an image capturing device 304 , e.g., an endoscope, or the like. Each of the two other arm assemblies 10 , 10 respectively, includes a surgical instrument 14 . The endoscope 304 has a viewing end 306 at a remote end of an elongate shaft thereof. It will be appreciated that the endoscope 304 has an elongate shaft to permit it to be inserted into an internal surgical site of a patient's body. The endoscope 304 is operatively connected to the viewer 202 to display an image captured at its viewing end 306 on the viewer 202 . Each robotic arm assembly 10 , 10 is operatively connected to one of the master controls. Thus, movement of the robotic arm assemblies 10 , 10 is controlled by manipulation of the master controls. The instruments 14 of the robotic arm assemblies 10 , 10 have end effectors which are mounted on working ends of elongate shafts of the instruments 14 . It will be appreciated that the instruments 14 have elongate shafts to permit the end effectors to be inserted into an internal surgical site of a patient's body. The end effectors are orientationally moveable relative to the ends of the shafts of the instruments 14 . The orientational movement of the end effectors are also controlled by the master controls.
[0049] In FIGS. 2A and 2B of the drawings, one of the robotic arm assemblies 10 is shown in greater detail.
[0050] The assembly 10 includes an articulated robotic arm 12 , and the surgical instrument, schematically and generally indicated by reference numeral 14 , mounted thereon. FIG. 3 indicates the general appearance of the surgical instrument 14 in greater detail.
[0051] In FIG. 3 the elongate shaft of the instrument 14 is indicated by reference numeral 14 . 1 . A wrist-like mechanism, generally indicated by reference numeral 50 , is located at the working end of the shaft 14 . 1 . A housing 53 , arranged releasably to couple the instrument 14 to the robotic arm 12 , is located at an opposed end of the shaft 14 . 1 . In FIG. 2A , and when the instrument 14 is coupled or mounted on the robotic arm 12 , the shaft 14 . 1 extends along an axis indicated at 14 . 2 . The instrument 14 is typically releasably mounted on a carriage 11 , which is selectively driven to translate along a linear guide formation 24 of the arm 12 in the direction of arrows P.
[0052] The robotic arm 12 is typically mounted on a base by means of a bracket or mounting plate 16 . The base is defined on the mobile cart or trolley 300 , which is normally retained in a stationary position during a surgical procedure.
[0053] The robotic arm 12 includes a cradle, generally indicated at 18 , an upper arm portion 20 , a forearm portion 22 and the guide formation 24 . The cradle 18 is pivotally mounted on the plate 16 gimbaled fashion to permit rocking movement of the cradle in the direction of arrows 26 as shown in FIG. 2B , about a pivot axis 28 . The upper arm portion 20 includes link members 30 , 32 and the forearm portion 22 includes link members 34 , 36 . The link members 30 , 32 are pivotally mounted on the cradle 18 and are pivotally connected to the link members 34 , 36 . The link members 34 , 36 are pivotally connected to the guide formation 24 . The pivotal connections between the link members 30 , 32 , 34 , 36 , the cradle 18 , and the guide formation 24 are arranged to constrain the robotic arm 12 to move in a specific manner. The movement of the robotic arm 12 is illustrated schematically in FIG. 4 .
[0054] With reference to FIG. 4 , the solid lines schematically indicate one position of the robotic arm 12 and the dashed lines indicate another possible position into which the arm 12 can be displaced from the position indicated in solid lines.
[0055] It will be understood that the axis 14 . 2 along which the shaft 14 . 1 of the instrument 14 extends when mounted on the robotic arm 12 pivots about a pivot center or fulcrum 49 . Thus, irrespective of the movement of the robotic arm 12 , the pivot center 49 normally remains in the same position relative to the stationary cart 300 on which the arm 12 is mounted during a surgical procedure. In use, the pivot center 49 is positioned at a port of entry into a patient's body when an internal surgical procedure is to be performed. It will be appreciated that the shaft 14 . 1 extends through such a port of entry, the wrist-like mechanism 50 then being positioned inside the patient's body. Thus, the general position of the mechanism 50 relative to the surgical site in a patient's body can be changed by movement of the arm 12 . Since the pivot center 49 is coincident with the port of entry, such movement of the arm does not excessively effect the surrounding tissue at the port of entry.
[0056] As can best be seen with reference to FIG. 4 , the robotic arm 12 provides three degrees of freedom of movement to the surgical instrument 14 when mounted thereon. These degrees of freedom of movement are firstly the gimbaled motion indicated by arrows 26 , pivoting movement as indicated by arrows 27 and the linear displacement in the direction of arrows P. Movement of the arm as indicated by arrows 26 , 27 and P is controlled by appropriately positioned actuators, e.g., electrical motors, which respond to inputs from an associated master control selectively to drive the arm 12 to positions as dictated by movement of the master control. Appropriately positioned sensors, e.g., encoders, potentiometers, or the like, are provided on the arm to enable a control system of the minimally invasive telesurgical system to determine joint positions.
[0057] Thus, by controlling movement of the robotic arm 12 , the position of the working end of the shaft 14 . 1 of the instrument 14 can be varied at the surgical site by the surgeon manipulating the associated master control while viewing the responsive positional movement of the working end of the shaft 14 . 1 in the viewer 202 .
[0058] Referring now to FIG. 5 of the drawings, the wrist-like mechanism 50 will now be described in greater detail. In FIG. 5 , the working end of the shaft 14 . 1 is indicated at 14 . 3 . The wrist-like mechanism 50 includes a wrist member 52 . One end portion of the wrist member 52 is pivotally mounted in a clevis, generally indicated at 17 , on the end 14 . 3 of the shaft 14 . 1 by means of a pivotal connection 54 . The wrist member 52 can pivot in the direction of arrows 56 about the pivotal connection 54 . An end effector, generally indicated by reference numeral 58 , is pivotally mounted on an opposed end of the wrist member 52 . The end effector 58 is in the form of, e.g., a clip applier for anchoring clips during a surgical procedure. Accordingly, the end effector 58 has two parts 58 . 1 , 58 . 2 together defining a jaw-like arrangement. It will be appreciated that the end effector can be in the form of any required surgical tool having two members or fingers which pivot relative to each other, such as scissors, pliers for use as needle drivers, or the like. Instead, it can include a single working member, e.g., a scalpel, cautery electrode, or the like. When a tool other than a clip applier is required during the surgical procedure, the tool 14 is simply removed from its associated arm and replaced with an instrument bearing the required end effector, e.g., a scissors, or pliers, or the like.
[0059] The end effector 58 is pivotally mounted in a clevis, generally indicated by reference numeral 19 , on an opposed end of the wrist member 52 , by means of a pivotal connection 60 . It will be appreciated that free ends 11 , 13 of the parts 58 . 1 , 58 . 2 are angularly displaceable about the pivotal connection 60 toward and away from each other as indicated by arrows 62 , 63 . It will further be appreciated that the members 58 . 1 , 58 . 2 can be displaced angularly about the pivotal connection 60 to change the orientation of the end effector 58 as a whole, relative to the wrist member 52 . Thus, each part 58 . 1 , 58 . 2 is angularly displaceable about the pivotal connection 60 independently of the other, so that the end effector 58 , as a whole, is angularly displaceable about the pivotal connection 60 as indicated in dashed lines in FIG. 5 . Furthermore, the shaft 14 . 1 is rotatably mounted on the housing 53 for rotation as indicated by the arrows 59 . Thus, the end effector 58 has three orientational degrees of freedom of movement relative to the working end 14 . 3 , namely, rotation about the axis 14 . 2 as indicated by arrows 59 , angular displacement as a whole about the pivot 60 and angular displacement about the pivot 54 as indicated by arrows 56 . It will be appreciated that orientational movement of the end effector 58 is controlled by appropriately positioned electrical motors which respond to inputs from the associated master control to drive the end effector 58 to a desired orientation as dictated by movement of the master control. Furthermore, appropriately positioned sensors, e.g., encoders, or potentiometers, or the like, are provided to permit the control system of the minimally invasive telesurgical system to determine joint positions.
[0060] In use, and as schematically indicated in FIG. 7 of the drawings, the surgeon views the surgical site through the viewer 202 . The end effector 58 carried on each arm 12 is caused to perform movements and actions in response to movement and action inputs of its associated master control. It will be appreciated that during a surgical procedure responsive movement of the robotic arm 12 on which the surgical instrument 14 is mounted causes the end effector to vary its position at the surgical site whilst responsive movement of the end effector relative to the end 14 . 3 of the shaft 14 . 1 causes its orientation to vary relative to the end 14 . 3 of the shaft 14 . 1 . Naturally, during the course of the surgical procedure the orientation and position of the end effector is constantly changing in response to master control inputs. The images of the end effectors 58 are captured by the endoscope together with the surgical site and are displayed on the viewer 202 so that the surgeon sees the positional and orientational movements and actions of the end effectors 58 as he or she controls such movements and actions by means of the master control devices.
[0061] An example of one of the master control devices is shown in FIG. 6C and is generally indicated by reference numeral 700 . The master control 700 includes a hand-held part or wrist gimbal 699 and an articulated arm portion 712 . The hand-held part 699 will now be described in greater detail with reference to FIG. 6A .
[0062] The part 699 has an articulated arm portion including a plurality of members or links 702 connected together by joints 704 . The surgeon grips the part 699 by positioning his or her thumb and index finger over a pincher formation 706 of the part 699 . The surgeon's thumb and index finger are typically held on the pincher formation 706 by straps (not shown) threaded through slots 710 . The joints of the part 699 are operatively connected to electric motors to provide for, e.g., force feedback, gravity compensation, and/or the like. Furthermore, appropriately positioned sensors, e.g., encoders, or potentiometers, or the like, are positioned on each joint of the part 699 , so as to enable joint positions of the part 699 to be determined by the control system.
[0063] The part 699 is mounted on the articulated arm portion 712 indicated in FIG. 6B . Reference numeral 4 in FIGS. 6A and 6B indicates the positions at which the part 699 and the articulated arm 712 are connected together. When connected together, the part 699 can displace angularly about an axis at 4 .
[0064] Referring now to FIG. 6B , the articulated arm 712 includes a plurality of links 714 connected together at joints 716 . Articulated arm 712 may have appropriately positioned electric motors to provide for, e.g., force feedback, gravity compensation, and/or the like. Furthermore, appropriately positioned sensors, e.g., encoders, or potentiometers, or the like, are positioned on the joints 716 so as to enable joint positions of the master control to be determined by the control system.
[0065] When the pincher formation 706 is squeezed between the thumb and index finger, the fingers of the end effector 58 close. When the thumb and index finger are moved apart the fingers 58 . 1 , 58 . 2 of the end effector 58 move apart in sympathy with the moving apart of the pincher formation 706 . To cause the orientation of the end effector 58 to change, the surgeon simply causes the pincher formation 706 to change its orientation relative to the end of the articulated arm portion 712 . To cause the position of the end effector 58 to change, the surgeon simply moves the pincher formation 706 to cause the position of the articulated arm portion 712 to change.
[0066] The electric motors and sensors associated with each robotic arm 12 and the surgical instrument 14 mounted thereon, and the electric motors and the sensors associated with each master control device 700 , namely the part 699 and the articulated arm portion 712 , are operatively linked in the control system (not shown). The control system typically includes at least one processor for effecting control between master control device input and responsive robotic arm and surgical instrument output and for effecting control between robotic arm and surgical instrument input and responsive master control output in the case of, e.g., force feedback.
[0067] As can best be seen in FIG. 6C , each master control device 700 is typically mounted on the control station 200 by means of a pivotal connection, as indicated at 717 . As mentioned hereinbefore, to manipulate each master control device 700 , the surgeon positions his thumb and index finger over the pincher formation 706 . The pincher formation 706 is positioned at a free end of the articulated arm portion of the part 699 , which in turn is positioned on a free end of the articulated arm 712 . It will be appreciated that the master control device 700 has a center of gravity normally removed from the vertical relative to its pivotal connection 717 on the control station 200 . Thus, should the surgeon let go of the pincher formation 706 , the master control device 700 would drop due to gravity. It has been found that providing the master controls 700 , 700 with gravity compensation so that whenever the surgeon lets go of the pincher formations 706 , 706 , the master controls 700 , 700 remain at their positions and orientations is beneficial. Furthermore, since performing surgical procedures involves precision movements, it is beneficial that the surgeon does not need to cope with a weighted feeling when gripping the pincher formations 706 , 706 of the master controls 700 , 700 . Thus, the control system of the telesurgical minimally invasive system is arranged to provide gravity compensation to the master control devices 700 , 700 . This gravity compensation can be achieved passively by use of counterbalancers, and/or springs, and/or the like, and/or actively by appropriate application of forces or torques on the motors operatively associated with each master control 700 . In the present case, the gravity compensation is achieved actively by means of appropriate compensating torques on motors associated with each master control 700 .
[0068] It will be appreciated that operative connection between the electrical motors and the master controls 700 , 700 , is typically achieved by means of transmissional components. These transmissional components typically include gear trains. Naturally, other transmissional components such as pulley and cable arrangements, and/or the like, can be used instead, or in addition. Regardless of the specific transmission used, these components will generally induce both static and dynamic friction in the telesurgical system.
[0069] It has been found that in providing gravity compensation, the gear trains between the motors and the master controls are typically under load. This increases the frictional forces between meshing gears and leads to increased friction when the master control is moved or urged to move by the surgeon. It has been found that the increase in frictional forces, due to gravity compensation in particular, renders master control movement uncomfortable and unpleasant (and may lead to imprecise movements) due to hysteresis.
[0070] Referring to FIG. 8 of the drawings, a typical graphical relationship between velocity and a desired force for compensation of friction is indicated by reference numeral 510 . Velocity is indicated on the horizontally extending axis and the required compensating frictional force is indicated on the vertically extending axis. To the left of the vertical axis a force in an arbitrary negative direction is indicated, and to the right of the vertical axis a force in an arbitrary positive direction is indicated. When movement is to be induced from a rest position, the force required to induce movement from rest is normally higher than that required to maintain movement after movement is initiated. This characteristic of friction is indicated by the opposed “spikes” at 512 in FIG. 8 , and is referred to as “stiction.” The spikes have been indicated in extended fashion along the velocity axis for the sake of clarity. However, it is to be appreciated that the spikes normally occur on the force axis and need not extend along the velocity axis as indicated. Note that the dynamic friction forces may not be perfectly constant, but may vary with velocity. When movement is initiated friction can readily be compensated for by applying a corresponding compensating force. However, to achieve adequate friction compensation when initiating movement from rest, or when changing direction, is more problematic.
[0071] A first friction compensation technique can best be described with reference to the following simple electromechanical system, by way of example. The example of the electromechanical system includes a motor and an articulated arm. The motor is arranged to drive the articulated arm through a transmission arrangement, e.g., a gear train, or the like. For the sake of this example, the graphical relationship between velocity and frictional force shown in FIG. 8 represents the mechanical friction in the electromechanical system as a function of velocity. It is generally desirable to compensate for this friction within the electromechanical system, as the friction can be distracting to the operator, limiting the operator's dexterity and effectiveness.
[0072] One method of compensating for friction, in particular for compensating for stiction, when the arm of the example is at rest, is to inhibit the electromechanical system from ever fully being at rest. This method includes cyclically supplying a current to the motor to prevent the electromechanical system from fully coming to rest. Thus, the motor is caused cyclically to move angularly in opposed directions. Thus a cyclical torque is supplied to the motor causing the slave to oscillate. This method is referred to as “dithering.”
[0073] Although this method inhibits the system from coming to rest and thus obviates stiction when movement is to be induced from a rest position, it has been found that dithering causes vibration in the system which is uncomfortable in some applications, particularly in minimally invasive surgical procedures. Furthermore, dithering can lead to excessive wear and ultimately damage to the apparatus.
[0074] Another method of compensating for friction is represented in FIG. 9 . This method involves supplying a force of a magnitude approximating the frictional force in the system whenever it is in motion. This type of compensation is referred to as “Coulomb” friction compensation. Such a force is induced in the electromechanical system by means of motor torque of a magnitude corresponding to the frictional force required to maintain movement in a specific direction after movement is achieved in that direction. The compensating force is indicated in dashed lines by reference numeral 520 with the sign of the compensating force being determined by the sign of the measured velocity.
[0075] This method also does not make allowance for the spikes at 512 . Thus, a degree of “sticking,” or stiction, is still felt when movement is initiated. Since it is difficult to measure velocity accurately when a system is at rest due to measurement inaccuracies, noise, and the like, it is problematic in applying the compensating force in the correct direction. Accordingly, when movement is to be initiated in one direction from rest, the system could be measuring a velocity in the opposed direction, in which case the compensating force is applied in the same direction as the frictional force thus aggravating stiction. Should the velocity reading fluctuate at zero, a compensating force which fluctuates in opposed directions is generated which introduces unpredictable energy into the system tending to destabilize it and giving it an active “feel.”
[0076] Another method of compensating for friction is indicated in FIG. 10 in dashed lines generally indicated by reference numeral 530 . This method is similar to the “Coulomb” type of compensation. However, inaccuracy in measurement around a zero velocity reading is compensated for by slanting the compensation across zero velocity. Although this method compensates for system uncertainty at zero velocity, it does not always accurately compensate for friction forces at low velocity, nor compensate for stiction when movement is to be initiated from rest. Thus, stiction is normally still present.
[0077] The preferred method of compensating for friction in accordance with the invention will now be described with particular reference to compensating for friction in a gear train of one of the master controls 700 , 700 due to gravity compensation. It will be appreciated that the description which follows is by way of example only and that the method of compensating for friction is not limited to this application only, but can be readily adapted to compensate for other sources of friction such as, e.g., at pivotal joints, between components which translate relative to each other, and/or the like. Furthermore, the method can enjoy universal application to compensate for friction in any system whether to compensate for friction due to gravity compensation or merely to compensate for friction in general irrespective of the source. For example, gear train loads imposed for purposes other than gravity compensation, for example, by a controller other than gravity controller, may induce friction that can be compensated for.
[0078] The method of compensating for friction in accordance with the invention can be understood with reference to a single joint of the master control 700 , for example the joint 704 B in FIG. 6B of the drawings, and an electrical motor associated with that joint through a gear train. It will be appreciated that friction compensation can be provided for each joint of the master control 700 .
[0079] Referring to FIG. 11 of the drawings, a graphical relationship between angular velocity (v) of the joint 704 B (as measured by the control system) and the force (f) which will compensate for force in the gear train associated with the joint 704 B is generally indicated by reference numeral 110 . Velocity (v) extends along the horizontal axis and the required force (f) to compensate for friction in the gear train extends along the vertical axis.
[0080] It has been found that when the arm members or links 702 A connected together by means of the joint 704 B are in a stationary position relative to one another, and the surgeon wishes to move the master control 700 in a manner initiating movement of the arm members 702 A about the joint 704 B, friction is particularly evident. The reason for this is that the force required to overcome friction from a stationary position is higher than the force required to maintain movement after movement is achieved. As soon as movement is achieved, the frictional force decreases and then stays approximately constant as velocity increases. This phenomenon is schematically indicated by the opposed spikes at 112 around the zero velocity region and is termed stiction. Once movement is achieved, the frictional force requiring compensation is generally constant as indicated by the straight line portions 114 .
[0081] It will be appreciated that movement of the pincher formation 706 is achieved through a plurality of joints, namely joints 704 , 716 and 717 . Thus, during any given pincher formation movement any one or more of the joints 704 , 716 , 717 may be at rest so that initiating movement about an arbitrary stationary joint or joints may be required while the pincher formation is actually moving. Thus, since there are a plurality of joints, stiction has a cumulative effect which renders precise movement of the master 700 difficult to maintain even while the pincher formation 706 is actually moving. When the pincher formation 706 is to be moved very slowly, stiction of any one or more of the joints 704 , 716 and 717 is particularly problematic and renders precise movement of the pincher formation 706 (and also responsive movement by the end effector 58 ) difficult to maintain. In fact, smooth motion of pincher formation 706 will involve directional changes of some of the joints. This can lead to significant changes in the cumulative friction force, again rendering precise movements difficult to maintain. To overcome or compensate for stiction and the differences between static and dynamic frictional forces is particularly advantageous, since slow precise movements are often employed during a surgical procedure. Compensating for stiction and the static/dynamic differential is also particularly problematic. One reason for this is that available sensors used to measure angular velocity are not entirely accurate so that precisely measuring zero velocity of the joint when at rest is difficult. Another reason is that noise may be superimposed on the sensor signal which further aggravates the problem of measuring zero velocity when the joint is at rest. Thus, when the joint is at rest, the sensors can be registering movement and, consequently, apparent velocity.
[0082] The joint can move in an arbitrary positive and an arbitrary negative direction. The velocity reading may have a negative value, a positive value, or may be fluctuating about the zero velocity reading when the joint is at rest due to the noise and measurement inaccuracies. If the velocity reading is used to determine a frictional compensation force, it is difficult to determine when and in what direction to apply the frictional force since the velocity reading does not correspond with the actual velocity of the joint particularly when the joint is at rest. Even with an accurate velocity measurement, using a sensor which accurately measures zero velocity when the joint is actually at rest, it would still be problematic to apply a frictional compensation force to compensate for stiction since it is not easy to anticipate in which of the arbitrary positive and negative directions the joint will be moved.
[0083] To overcome these problems, and to compensate for stiction in particular whilst accommodating measurement inaccuracies, a velocity region indicated between the arrows X-X is chosen, such that if the velocity reading is within this region, a cyclical torque, varying in a positive and a negative direction is supplied to the motor so that irrespective of the direction in which movement is to be initiated from rest, a friction compensation torque is provided at least part of the time. This will be described in greater detail below.
[0084] The indicated velocity region X-X can be chosen based on measurement accuracy such that outside the region the joint is actually moving whilst inside the region the joint could either be moving very slowly in either direction or may be stationary. Outside the region X-X, it is assumed that the velocity reading does indicate joint movement in a correct direction and that movement has been initiated. A uniform compensating torque is then applied corresponding with the constant friction experienced when movement is achieved, as will be described in greater detail herein below.
[0085] Still referring to FIG. 11 of the drawings, the control system of the invention is arranged to generate compensating values determined by the velocity reading within the region X-X. This can best be explained by means of the slanted dashed line in FIG. 11 . The slanted dashed line DL extends between opposed intersections of the chosen velocity reading region X-X, and the required force for compensating for friction. Naturally, the slanted line need not be linear but could be rounded at its comers, and/or the like. Furthermore, the width of the region between X-X can be tailored to suit the system friction characteristics.
[0086] The friction compensating force values along dashed line DL can be represented as percentages for generating a duty cycle appropriate to a measured velocity. Should the velocity reading be at +v1 a force value of 100% is generated. Similarly, if the velocity reading is at −v1, a value of 0% is generated. In similar fashion a specific value ranging between 0% and 100% is generated depending upon the measured velocity reading position between +v1 and −v1.
[0087] The value thus generated can be used to determine a duty cycle signal distribution between the arbitrary positive and the arbitrary negative direction of movement about the joint 704 B. Thus, where a value of 0% is generated, the reading then being negative, in other words, in an arbitrary negative direction, a duty cycle as indicated in FIG. 12 is generated. The distribution of the duty cycle in FIG. 12 is correspondingly fully negative, or 100% negative. The region X-X can be chosen such that at this point, taking noise and measurement inaccuracies into account, the master may be either about to actually move in the negative direction or may already be moving in the negative direction.
[0088] Similarly, should a value of 20% be generated, for example, a duty cycle as indicated in FIG. 13 is generated. The distribution of the duty cycle in FIG. 13 is correspondingly 20% positive and 80% negative.
[0089] Should a value of 50% be generated, a duty cycle as indicated in FIG. 14 is generated. The distribution of the duty cycle in FIG. 14 is correspondingly 50% positive and 50% negative.
[0090] Similarly, should a value of 80% be generated, a duty cycle as indicated in FIG. 15 is generated. The distribution of the duty cycle in FIG. 15 is correspondingly 80% positive and 20% negative.
[0091] In the case where a value of 100% is generated, a duty cycle as indicated in FIG. 16 is generated. The distribution of the duty cycle in FIG. 16 is correspondingly fully positive, or 100% positive. At this point, taking noise and measurement inaccuracies into account, the master can be either about to actually move in the positive direction or may already be moving in the positive direction.
[0092] It will be appreciated that the duty cycles shown need not necessarily have generally rectangular waveforms.
[0093] It will further be appreciated that when the joint is at rest, the velocity reading is typically fluctuating within the X-X region so that the duty cycle distribution is continually varying.
[0094] The method of compensating for friction will now be described in further detail with reference to FIG. 17 .
[0095] In FIG. 17 , a block diagram indicating steps corresponding to the method of compensating for friction in accordance with the invention is generally indicated by reference numeral 410 .
[0096] The velocity readings as described above are indicated at 412 . The compensating values determined from the velocity readings is indicated at 414 . The compensating values are input to a duty cycle generator such as a PWM generator at 416 . The resultant duty cycle signal distribution is output from the PWM generator.
[0097] It will be appreciated that the steps from 412 to 416 are used to determine only the percentage distribution of the duty cycle signal between the arbitrary negative and positive joint movement directions. This determination is directly related to the velocity measurements between arrows XX. The determination of the amplitude or magnitude of the duty cycle signal will now be described.
[0098] As mentioned earlier, the control system compensates for gravity. The master control 700 is moveable about a pivot at 717 and the pincher formation 706 is connected to the pivot 717 through the joints 704 , 716 and the intervening arm members. The master control 700 as a whole is thus displaceable about the pivot 717 . A horizontal component of the center of gravity varies as the pincher formation 706 is displaced. Accordingly, the torque supplied to an electrical motor operatively associated with the master control 700 and which balances and compensates for gravity also varies. Thus, the gravity compensating torque on the electrical motor is determined in part by the position of the center of gravity. This is indicated schematically in FIG. 20 of the drawings by way of example. In FIG. 20 , it can be seen that the torque required on a motor M 1 to hold an arm A 10 in a position as indicated in solid lines to compensate for gravity is greater than that required to hold the arm in the position indicated in dashed lines. A similar principal applies for each joint of the master control 700 . Naturally, the higher the gravity compensating torque supplied to the motor, the higher the transmission loading on the associated gear train and therefor the higher the frictional force and vice versa.
[0099] Each joint 704 , 716 , 717 may have an actuator, e.g., electric motor, operatively associated therewith to provide for, e.g., force feedback. Furthermore, for each joint employing gravity compensation, a corresponding gravity compensating torque is supplied to the motor operatively associated therewith. The gravity compensation torque magnitude varies depending on master control position. The motor operatively associated with each joint employing gravity compensation can be provided with a friction compensation torque in accordance with the method of the invention. The friction compensation torque magnitude applied to a particular joint varies in accordance with the gravity compensation torque. It will be appreciated that the effects of friction can be negligible on some of the joints. Hence, friction compensation may not be provided for all joints of the master and/or slave.
[0100] The friction compensation loads induced by the gravity compensation system need not, and generally will not, be applied separately. The exemplary friction compensation system described herein incorporates the gravity model, so that the gravity compensation torques become part of the load applied by the friction compensation system. Alternatively, separate gravity compensation and friction compensation loads might be maintained.
[0101] Referring once again to FIG. 17 of the drawings, a gravity compensating model is indicated at 418 whereby gravity compensation forces for the joints requiring gravity compensation are determined. For each of the joints 704 , 716 , 717 employing gravity compensation, the gravity compensation model determines the torque which can hold the part of the master control 700 extending from that joint in the direction of the pincher formation 706 in a stationary position. Naturally, this torque varies for each joint in sympathy with positional variation of that joint as the master control 700 is moved from one position to a next position.
[0102] Referring now to FIG. 18 of the drawings, the gravity and friction (efficiency) model 418 will now be described in greater detail. From the gravity model, indicated at 419 , the magnitude of a desired gravity compensating force for the joint, e.g., joint 704 B, is determined. The gravity compensating force is then forwarded to a friction compensation determining block 451 for determining friction compensation in the arbitrary positive joint movement direction as indicated by line 452 . The gravity compensation force is also forwarded to a friction compensation determining block 453 for determining friction compensation in the arbitrary negative joint movement direction as indicated by line 454 .
[0103] In the block 451 , the magnitude of the gravity compensating force is represented along a horizontally extending axis and the corresponding required frictional compensating force for the positive joint movement direction is represented along a vertically extending axis. The corresponding frictional compensating force is determined taking the gear train efficiency into account as indicated by the lines 1/eff and eff, respectively (eff being efficiency, typically less than 1).
[0104] In similar fashion, in the block 453 , the magnitude of the gravity compensating force is represented along a horizontally extending axis and the corresponding required frictional compensating force for the negative joint movement direction is represented along a vertically extending axis. The corresponding frictional compensating force is determined taking the gear train efficiency into account as indicated by the lines 1/eff and eff, respectively.
[0105] The magnitudes of the frictional compensating forces in respectively the positive and the negative joint movement directions determined in the blocks 451 , 453 represent the magnitudes of the frictional forces in respectively the positive and negative joint movement directions after movement of the joint has been initiated. Thus, they correspond with the lines 114 in FIG. 11 of the drawings.
[0106] The magnitude of these forces are used to determine the amplitude of the duty cycle signal at 416 . Thus, from 414 the percentage distribution between the arbitrary positive and negative directions were determined, and from the gravity model at 418 , the magnitude or amplitude of the duty cycle signal is determined for each arbitrary positive and negative joint movement direction. It will be appreciated that these magnitudes correspond to dynamic friction compensating forces. Depending on actual joint position, these compensating forces can be dissimilar.
[0107] As mentioned earlier, overcoming friction when at rest involves a higher force than is applied to maintain movement. This characteristic of friction is compensated for at 420 when the velocity reading lies in the region Y-Y as indicated (also designated as the region between −V2 and V2). The force which can cause an object, in this case the meshing gears of the gear train, to break away from a rest position is typically some factor higher than 1, often being about 1.6 times the force to maintain movement after movement is achieved. This factor can vary depending on the application. In this case, the factor or ratio corresponds to the relationship between the force which will overcome friction in the gear train when at rest and to maintain movement in the gear train once movement has been initiated. More specifically, the ratio corresponds to the change in efficiency of the gear train when at rest versus when in motion. It will be appreciated that at 420 , the ratio and effective range Y-Y can be tailored to suit a specific application. The range Y-Y could correspond with the range X-X, for example.
[0108] Referring now to 420 in greater detail, and assuming the region Y-Y corresponds with the region X-X, at 0% and 100% values, a factor of 1 is generated. At a 50% value a maximum factor is generated. Between 50% and 100% and between 50% and 0% a linear relationship between the maximum factor value, in one example 1.6, and the minimum factor value, namely 1, is established. Thus, at a value of 75% or 25% a factor of 1.3 would be generated. It will be appreciated that the relationship need not necessarily be linear.
[0109] The factor ranging between 1 and the maximum factor determined at 420 from the velocity reading is then output or forwarded to factoring or adjusting blocks at 422 and 421 , respectively.
[0110] The friction compensation force for movement in the positive joint direction is input to the block 422 as indicated by line 424 . In the block 422 , this friction compensation value is indicated along the horizontal axis. The actual friction compensation force magnitude to compensate for stictions is indicated along the vertical axis. The value of the factor is indicated by the letters “fac.” This value determines the relationship between the actual required friction compensation forces and the friction force requiring compensation when movement in the positive joint direction is achieved. Thus, the value fac determines the gradient of the lines indicated by fac and 1/fac, respectively. Naturally, when fac=1, the lines fac and 1/fac extend at 45° resulting in the actual required friction being equal to the friction requiring compensation. This corresponds with a condition in which the velocity reading is outside or equal to the outer limits of the Y-Y region. It will be appreciated that at 421 , a similar adjustment takes place for friction compensation force in the negative direction.
[0111] It will be appreciated that a larger force to compensate for friction in one direction may be required than in the opposed direction, in particular because our compensation torque here indicates both friction compensation torque and gravity compensation torque. This depends on the actual position of the joint. Normally, to cause the arm member extending from the joint toward the pincher formation 706 to move in an operatively downward direction requires less friction compensation torque than moving it in an operatively upward direction. Thus, should the arbitrary positive joint movement direction correspond with an upward movement, a greater frictional compensating force is required than that in the arbitrary negative direction, and vice versa. Thus, the amplitude of the duty cycle can be higher or lower on the positive side than the negative side depending on the position of the joint, and whether the arbitrary positive joint movement direction corresponds with an upward or downward movement of the arm member extending from the joint. Indeed, the “positive” compensation load need not be in the positive direction and the “negative” load need not be in the negative direction, although the positive load will be greater than or equal to the negative load.
[0112] After the friction compensation force magnitudes have been determined in this manner, they are forwarded to the PWM signal generator at 416 as indicated by lines 462 and 464 , respectively. At the PWM signal generator, the force magnitudes are combined with the duty cycle distribution signal determined at 414 to determine a resultant duty cycle signal as indicated at 466 . The resultant duty cycle signal 466 is then passed from the PWM signal generator along line 468 .
[0113] The duty cycle signal thus determined by the PWM signal generator 416 by combining outputs from 414 , 421 and 422 is then passed to an amplifier so that the required electrical current can be passed to the electrical motor operatively associated with the joint 704 B so as to generate corresponding cyclical torques on that motor.
[0114] The frequency of the duty cycle output from 416 is predetermined so as to be low enough to enable the electrical motor to respond and high enough so as not to be felt mechanically. Thus, the frequency is greater than the mechanical time constants of the system yet less than the electrical time constants of the electric motor. A suitable frequency in the exemplary telesurgical system falls in the range between 40 Hz to 70 Hz, preferably about 55 Hz.
[0115] It will be appreciated that where it is possible accurately to read zero velocity when the master control 700 is at rest, the above method of compensating for friction can also be used. For example, when the master control 700 is stationary and a zero velocity reading is measured, a duty cycle is forwarded to the motors, the duty cycle having a magnitude corresponding to the required frictional compensating force and having a 50% distribution. Thus, when an external force is applied to the hand control by the surgeon in a specific direction, a friction compensating force is delivered 50% of the time to assist in initiating movement of the master control 700 , thus to compensate for stiction. As movement is then induced and the velocity reading increases in a specific direction, the distribution of the cycle changes in a direction corresponding to the direction of movement of the master control. Eventually, when the master control is being moved at a velocity corresponding to a velocity reading outside the range XX, the compensating force, or torque to the motors, is distributed 100% in a direction corresponding to the direction of movement of the master control. The duty cycle has a predetermined frequency so that, irrespective of the direction of required movement induced on the master control 700 when the master control 700 is moved, e.g., by the surgeon's hand, a corresponding friction compensating force is supplied at a percentage of the time determined by the velocity reading. The effect of this is that during movement initiation, the sticking sensation is compensated for. This enables smooth precision movements to be induced on the master control without sticking, particularly at small velocities.
[0116] As mentioned, the method of compensating for friction is not limited to friction resulting from gravity compensation. In other words, gravity model might be replaced by some other controller determining torques to be applied to the motors for another purpose. The method can be used to compensate for friction per se.
[0117] Referring now to FIG. 19 , a method of compensating for friction as applied to friction per se will now be described. The method is similar to the method described above with reference to gravity compensation. However, in this case, the gravity model is replaced by a Coulomb friction model which provides a fixed compensating friction value in the arbitrary positive and negative joint movement directions. The fixed compensating friction can be set to correspond with an actual constant friction value for friction compensation as defined by actual system parameters. The adjustment factor simply may multiply these fixed values in 421 and 422 . This method can be used to overcome actual friction in the joint itself, for example, should the friction in the joint require compensation. In other respects, the method of compensating for friction, and stiction, as discussed above applies. Hence, this method can be combined with the system described above or with another gravity and/or friction model using appropriate adjustments 421 and 422 .
[0118] While the exemplary embodiment has been described in some detail, by way of example and for clarity of understanding, a variety of changes and modifications will be obvious to those of skill in the art. Hence, the scope of the present invention is limited solely by the appended claims. | Devices, systems, and methods for compensate for friction within powered automatic systems, particularly for telesurgery and other telepresence applications. Dynamic friction compensation may comprise applying a continuous load in the direction of movement of a joint, and static friction compensation may comprise applying alternating loads in positive and negative joint actuation directions whenever the joint velocity reading falls within a low velocity range. | 0 |
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a divisional of U.S. application Ser. No. 13/984,646 filed on Aug. 9, 2013, now issued as U.S. Pat. No. 9,040,669, which is a national phase filing under 35 U.S.C. §371 of PCT International Application PCT/US2012/024885, filed Feb. 13, 2012, and published under PCT Article 21(2) in English as WO2012/109659 on Aug. 16, 2012. This application also claims priority from U.S. Provisional Application No. 61/463,082, filed Feb. 11, 2011, entitled GENERATION AND USE OF HLA-A2 RESTRICTED, PEPTIDE-SPECIFIC MONOCLONAL ANTIBODIES AND CHIMERIC ANTIGEN RECEPTORS. The contents of each of these applications are hereby incorporated by reference in their entirety into the present disclosure.
SEQUENCE LISTING
The instant application contains a Sequence Listing, created on Jan. 20, 2016; the file, in ASCII format, is designated 3314019BSequenceListing.txt and is 51,295 bytes in size. The file is hereby incorporated by reference in its entirety into the instant application.
BACKGROUND OF THE INVENTION
1. Technical Field
The present invention relates generally to antigen-binding protein molecules involved in immune function. More particularly, the present invention relates to recombinant antibodies, chimeric antigen receptors and fragments thereof with specificity for an HLA-restricted peptide, where the peptide is derived from a cellular or viral protein of interest.
2. Background Information
Advances in adoptive T cell immunotherapy have led to several promising options for cancer patients in the past decade. T-cell based immunotherapy for cancer stemmed from studies which showed a correlation of increased numbers of tumor infiltrating lymphocytes (TILs) in surgical specimens and patient outcome. It is generally believed that this infiltration of TILs represents activation of an anti-tumor mechanism and that the infiltration was mediated through the expression of tumor associated antigens in the context of MHC. These findings eventually led researchers to try and take advantage of antigen-specific T cells for the treatment of cancer.
For induction of cytotoxic T-cell (CTL) responses, intracellular proteins are usually degraded by the proteasome or endo/lysosomes, and the resulting peptide fragments bind to MHC class I or II molecules. These peptide-MHC complexes are displayed at the cell surface where they provide targets for T cell recognition via a peptide-MHC (pMHC)-T cell receptor (TCR) interaction. Vaccinations with peptides derived from cellular and viral protein can induce HLA-A0201-restricted cytotoxic CD8 T cells, which are capable of killing tumor cells or virally-infected cells.
Antibodies are increasingly being used as therapeutic agents to fight cancer, autoimmune disease and infection. Therapeutic antibodies have been exploited based on their multiple mechanisms of action, which include the following: 1) naked antibodies killing tumor cells directly by ADCC or CDC (e.g. trastuzumab), 2) blocking or stimulating a cell membrane molecule to induce cell death (e.g. cetuximab), 3) neutralizing a secreted moiety (e.g. bevacizumab), 4) killing via an attached moiety such as a drug, toxin, radioisotope and 5) modulating the immune system via T cell effector functions.
In almost all cases, to generate a therapeutic benefit, antibodies have to possess critical properties including high affinity for their targeted antigen, minimal acute and long-term side effects, and in specific applications, high affinity for human Fc receptors (4). In addition, the targeted antigen has to be expressed at high levels on tumors but not on normal tissues (specificity or selectivity), consistently expressed in the specific tumor among patients and within patients (low heterogeneity), and should either be essential for the survival of the cancer cell or unlikely to be down regulated.
To achieve these attributes, researchers can now reengineer existing antibodies to make them less immunogenic, modifying both protein and carbohydrate residues in the Fc regions to enhance ADCC and CDC, shrinking their sizes for potentially better tumor penetration, mutating the variable regions to improve affinity, increasing avidity by changing antibody valency, and constructing novel antibody-fusion proteins such as those for multi-step targeting (5) and for redirecting immune cells by way of a chimeric antigen receptor (CAR). Furthermore, researchers continue to define the structural attributes and the host characteristics responsible for success among currently approved antibodies (6).
With the objective of eliminating or neutralizing the pathogenic agent or disease target, including bacterial, viral or tumor targets, antigen-specific, antibody-based treatments are particularly attractive because of the antibody's exquisite specificity.
SUMMARY OF THE INVENTION
The present invention, therefore, is based on the identification of antigen-specific binding sequences from which a variety of antigen-binding proteins can be produced, for example, an antibody specific for an antigen that represents a complex of a protein fragment (peptide) and an HLA molecule similar to that typically recognized by a T-cell receptor following antigen processing and presentation of the protein to the T-cell. Phage display is used to select an initial antigen-binding molecule that can be used to engineer the antigen-binding proteins of the invention, which include antibodies and chimeric antigen receptors (CARs).
In one aspect, therefore, the invention relates to an isolated antigen-binding protein or antigen-binding fragment thereof comprising one of:
(A) an antigen binding region having the amino acid sequence of one of SEQ ID NOS: 2, 5, 8, 10, 13, 14, 17, 20; (B) an antigen binding region comprising a V H and V L , respectively, with amino acid sequences selected from SEQ ID NOs: 22 and 23; 24 and 25; 26 and 27; 28 and 29; 30 and 31; 32 and 33; 34 and 35; and 36 and 37; or (C) (i) the following three light chain (LC) complementarity determining regions (CDRs): (a) a LC CDR1 comprising the amino acid sequence of SEQ ID NO: 56; and (b) a LC CDR2 and CDR3 comprising respectively, the amino acid sequence of SEQ ID NOs: 57 and 64, 58 and 65, 59 and 66, 60 and 67, 61 and 68, 61 and 69, 62 and 70 and 63 and 71; and
(ii) the following three heavy chain (HC) CDRs:
(a) a HC CDR1 comprising the amino acid sequence of SEQ ID NO: 38; and (b) a LC CDR2 and CDR3 comprising respectively the amino acid sequence of one of SEQ ID NOs: 40 and 48, 41 and 49, 42 and 50, 43 and 51, 44 and 52, 45 and 53, 46 and 54 and 47 and 55.
In a related aspect, the invention relates to an isolated antigen-binding protein or antigen-binding fragment thereof, wherein the isolated antigen-binding protein is an antibody or a chimeric antigen receptor. The antibody is a full-length antibody, a substantially intact antibody, a Fab fragment, a F(ab′) 2 fragment or a single chain variable fragment (scFv).
In the isolated antigen-binding protein, whether an antibody or CAR, the antigen-binding region specifically binds to an epitope of an HLA-peptide complex.
Peptides that are recognized by the antigen-binding proteins of the invention as part of an HLA-peptide complex include, but are not limited to, a peptide with the amino acid sequence RMFPNAPYL (SEQ ID NO:1); a peptide with the amino acid sequence LLDFVRFMGV (SEQ ID NO:4); a peptide with the amino acid sequence RLTRFLSRV (SEQ ID NO: 7); a peptide with the amino acid sequence RIITSTILV (SEQ ID NO: 12); and a peptide with the amino acid sequence LLEEMFLTV (SEQ ID NO:19). In some embodiments, the peptide is recognized in associate with an HLA-A2 antigen.
In yet another aspect, the isolated antigen-binding protein of the invention is a scFv comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 2, 5, 8, 10, 13, 14, 17 and 20.
In a related aspect, the isolated antigen-binding protein is a fusion protein comprising an antigen-binding region as disclosed in any of Tables 1-8.
In another aspect, the invention relates to an immunoconjugate comprising a first component which is an antigen-binding protein, or antigen-binding fragment thereof as disclosed herein. The immunoconjugate comprises a second component that is a cytotoxin, a detectable label, a radioisotope, a therapeutic agent, a binding protein or a molecule having a second amino acid sequence. Where the second component is a binding protein or second antibody, the binding protein or second antibody has binding specificity for a target that is different from the HLA-peptide complex.
In a related aspect, therefore, the present invention relates to bispecific antibody comprising an antigen-binding protein or functional fragment thereof as described herein.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows the binding of bacterial supernatant from individual EBNA3C scFv clones 315, 335, 327 and 345 ( FIG. 1A ) and purified EBNA clone 315 scFv (FIG. 1 B) to various HLA-A2-peptide complexes demonstrating that clone 315 is highly specific for the HLA-A2-LLDFVRFMGV (SEQ ID NO: 4) complex.
FIG. 2 shows the binding of bacterial supernatant from individual WT-1 scFv clones 42, 43 and 45 ( FIG. 2A ) and purified WT-1 clone 45 scFv ( FIG. 2B ) to various HLA-A2-peptide complexes demonstrating that WT-1 clones 42, 43 and 45 are highly specific for the recombinant HLA-A2-RMFPNAPYL (SEQ ID NO: 1) complex.
FIG. 3 shows that HLA-A2 can be detected on TAP-deficient (TAP − ) T2 cells that were either pulsed or unpulsed with LLDFVRFMGV (SEQ ID NO: 4) or another (irrelevant) peptide ( FIG. 3A ) but that EBNA clone 315 scFv recognizes T2 cells that have been pulsed with LLDFVRFMGV (SEQ ID NO: 4) but not unpulsed cells or cells pulsed with irrelevant peptide ( FIG. 3B ) with a lower limit of detection at about 78 nM ( FIG. 3C ).
FIG. 4 shows that HLA-A2 can be detected on TAP-deficient (TAP − ) T2 cells that were either pulsed or unpulsed with RMFPNAPYL (SEQ ID NO: 1) or LLDFVRFMGV (SEQ ID NO: 4) ( FIG. 4A ) but that WT-1 clone 45 scFv recognizes T2 cells that have been pulsed with RMFPNAPYL (SEQ ID NO: 1) but not unpulsed cells or cells pulsed with LLDFVRFMGV (SEQ ID NO: 4) ( FIG. 4B )
FIG. 5 shows that when DIMT ( FIG. 5A ) and 6268A ( FIG. 5B ) BLCLs are incubated with LLDFVRFMGV (SEQ ID NO: 4) (middle panel) or KLQCVDLHV (SEQ ID NO: 74) peptides (right panel) and stained with EBNA clone 315 scFv, only HLA-A2+DIMT peptide-pulsed with LLDFVRFMGV (SEQ ID NO: 4) could be stained, showing that EBNA clone 315 and LLDFVRFMGV (SEQ ID NO: 4) are HLA-A2 restricted; a time course ( FIG. 5C ) shows that the HLA-A2-LLDFVRFMGV (SEQ ID NO: 4) complex is stable on the cell surface.
FIG. 6 shows the Tomlinson library vector used in PCR to add appropriate restriction enzyme sites to either side of the WT1 Clone 45 and EBNA Clone 315 scFv sequences ( FIG. 6A ). FIG. 6B shows the digested PCR products as they appeared on a 1% agarose gel following digestion with NheI and ApaI.
FIG. 7 shows the full IgG expression vector ( FIG. 7A ) that was used to generate an expression vector for scFv-Fc fusion proteins ( FIG. 7B ). A. The structure of the proprietary IgG expression vector (11381 bp). The vector expresses the heavy and light chains under two separate CMV promoters. The variable heavy chain (V H ) is fused to the first, second and third constant heavy chains (CH 1, 2, 3 ) and expressed under one promoter while the variable light chain (V L ) is fused to the constant light chain (C L ) and expressed under a different promoter. This vector was further modified to lack the first constant region of the heavy chain (CH 1 ), and this vector was used for the construction of scFv-Fc fusion proteins. B. After excision of the V H from the IgG vector using NheI and ApaI, the pre-digested, purified scFv PCR products were ligated to the IgG vector to allow for the expression of the scFv fused to the CH 2, 3 domains (Fc).
FIG. 8 shows the results of binding studies using EBNA Clone 315 scFv-Fc in which purified EBNA Clone 315 scFv-Fc was shown to maintain its binding ability towards the recombinant complex when tested for binding on an ELISA plate coated with or without HLA-A2-LLDFVRFMGV (SEQ ID NO: 4) ( FIG. 8A ) and when tested for binding on T2 cells pulsed with or without the LLDFVRFMGV (SEQ ID NO: 4) peptide ( FIG. 8B ). When T2 cells were incubated with decreasing concentrations of the LLDFVRFMGV (SEQ ID NO: 4) peptide and subsequently stained with EBNA Clone 315 scFv-Fc, a lower limit of detection was demonstrated to be in the same range as the scFv (200 nM-20 nM) ( FIG. 8C ).
FIG. 9 shows the results of kinetics determination of EBNA Clone 315 to HLA-A2-LLDFVRFMGV (SEQ ID NO: 4) using surface plasmon resonance.
FIG. 10 shows the results of HLA-A2-LLDFVRFMGV (SEQ ID NO: 4) complex quantitation on T2 cells using fluorescently-conjugated EBNA Clone 315 scFv-Fc ( FIG. 10A ). Fluorescently-conjugated EBNA Clone 315 scFv-Fc was tested for binding on T2 cells pulsed with (20, 10, or 5 μM) or without (0 μM) the LLDFVRFMGV (SEQ ID NO: 4) peptide in serum-free IMDM media at 37° C. for 5 hours. The cells, in addition to beads containing known amounts of anti-human IgG 1 antibodies, were stained with the scFv-Fc and the cell's fluorescence intensity was correlated to that of the beads and their number of binding sites. Using these four peptide concentrations and corresponding number of complexes, a standard curve was created with an R 2 value of 0.9948. FIG. 10B shows a close-up view of the lower end of the peptide and complex spectrum.
FIG. 11 shows the results of binding and specificity studies when purified WT1 Clone 45 scFv-Fc was tested for binding on an ELISA plate coated with or without HLA-A2-RMFPNAPYL (SEQ ID NO: 1) ( FIG. 11A ). FIG. 11B shows that when purified WT1 Clone 45 scFv-Fc was tested for binding on T2 cells pulsed with the RMFPNAPYL (SEQ ID NO: 1) or RLTRFLSRV (SEQ ID NO: 7) peptide (40 μM), the scFv-Fc (unfilled lines) was only able to recognize RMFPNAPYL (SEQ ID NO: 7)-pulsed T2 cells.
FIG. 12 shows that when DIMT (top) and 6268A (bottom) BLCLs were incubated with RMFPNAPYL (SEQ ID NO: 1) (right panel) and the peptide-pulsed BLCLs were stained with WT1 Clone 315 scFv-Fc (unfilled lines) or a control scFv (filled lines), only the HLA-A2-positive RMFPNAPYL (SEQ ID NO: 1) peptide-pulsed DIMT BLCLs could be stained.
FIG. 13 shows EBNA Clone 315 scFv-Fc mediated ADCC (measured using 51 Cr release) of LLDFVRFMGV (SEQ ID NO: 4) peptide-pulsed cells.
FIG. 14 shows the MSCV-based vector (top left panel) containing an IRES-GFP sequence along with ampicilin-resistance used for transduction and expression of anti-EBNA CAR in NK92MI cells. The EBNA Clone 315 scFv sequence was cloned into the CAR gene (EBNA CAR) and further cloned into an MSCV-based vector (top left panel) which contained an IRES-GFP sequence along with ampicilin-resistance. The resulting CAR (top right panel) is composed of the scFv and hinge region on the extracellular surface, a transmembrane domain, along with 4-1 BB and the CD3ζ chain present within the cell. After retroviral packaging using 293T GP2 cells and transduction into NK92MI cells, approximately 24% of the NK92MI cells contained the construct based on GFP expression (bottom left panel; unfilled lines) when compared to mock transduced (empty retrovirus) NK92MI cells (bottom left panel; filled lines). Of the GFP-positive cells, the top 20% were flow cytometrically sorted and expanded to yield a population of stably transduced cells which were greater than 90% GFP positive (bottom right panel). Retroviral transduction was done on three separate occasions, with 24% being the highest efficiency.
FIG. 15 shows EcoRI and XhoI digestion validation of the WT1 Clone 45 CAR vector. FIG. 15A : Along with sequence validation, plasmids isolated from 8 different bacterial colonies, after ligation, transformation and EcoRI and XhoI digestion, were run on a 1% agarose gel. Based on the lambda HindIII and 100 bp markers, it was determined that the bands were the correct size (˜1500 bp and ˜6000 bp). FIG. 15B : The structure of the resulting WT1 Clone 45 CAR vector has the same components as the original St. Jude CAR vector with the only difference being the scFv sequence.
FIG. 16 shows that Clone 315 CAR-expressing NK92MI cells can specifically detect the HLA-A2-EBNA3C complex on peptide-pulsed T2 cells via CD107a expression. T2 cells were pulsed with or without LLDFVRFMGV (SEQ ID NO: 4) or YMFPNAPYL (SEQ ID NO: 76) peptides at 20 μM. CAR-equipped NK92MI cells were then cultured in media containing an anti-CD107a-PE conjugated antibody at 37° C. for 5 hours with or without peptide pulsed or unpulsed cells. FIG. 16A : CAR-equipped NK92MI cells were gated based on GFP fluorescence and analyzed for CD107a expression. NK92MI cells which were cultured without any T2 cells or those which were cocultured with unpulsed and YMFPNAPYL (SEQ ID NO: 76) -pulsed T2 cells were unreactive while NK92MI cells which were cocultured with LLDFVRFMGV (SEQ ID NO: 4)-pulsed T2 cells led to a 27% increase in CD107a expression above background levels. FIG. 16B : T2 cells were pulsed with decreasing concentrations of LLDFVRFMGV (SEQ ID NO: 4) and subsequently cocultured with CAR-equipped NK92MI cells. NK92MI cells presented noticeable amounts of CD107a on their cell surface even when T2 cells were pulsed with only 10 nM of peptide.
FIG. 17 shows the results of flow cytometry in which HLA-A2 + (DIMT) and HLA-A2 − (6268A) BLCLs were pulsed with LLDFVRFMGV (SEQ ID NO: 4) and CAR-equipped NK92MI cells were then cultured in media containing an anti-CD107a-PE conjugated antibody with or without peptide pulsed or unpulsed cells. CAR-equipped NK92MI cells were gated based on GFP fluorescence and analyzed for CD107a expression. NK92MI cells which were cultured without any BLCL or those which were cocultured with LLDFVRFMGV (SEQ ID NO: 4)-pulsed 6268A BLCL were unreactive while NK92MI cells which were cocultured with unpulsed DIMT BLCL or LLDFVRFMGV (SEQ ID NO: 4)-pulsed DIMT BLCL led to a 0.5% and 25% increase in CD107a expression above background levels (pulsed 6268A) showing that EBNA Clone 315 CAR-expressing NK92MI cells can specifically detect the HLA-A2-EBNA3C complex on peptide-pulsed BLCLs via CD107a expression.
FIG. 18 shows the results of a 51 Cr release assay in whichT2 cells were pulsed with or without decreasing concentrations of LLDFVRFMGV (SEQ ID NO: 4). CAR-equipped NK92MI cells were cocultured with 51 Cr-labeled T2 cells at a 3:1 E:T ratio demonstrating that EBNA Clone 315 CAR-expressing NK92MI cells can specifically detect the HLA-A2-EBNA3C complex on peptide-pulsed T2 cells. Even with 2 nM of peptide, peptide-specific cytotoxicity could be observed when compared to unpulsed T2 cells.
FIG. 19 shows EBNA Clone 315 CAR-expressing NK92MI cells can specifically detect the HLA-A2-EBNA3C complex on peptide-pulsed BLCLs via 51 Cr release. BLCLs were pulsed with LLDFVRFMGV (SEQ ID NO: 4). CAR-equipped NK92MI cells were then cultured with 51 Cr labeled target cells. FIG. 19A : CAR equipped NK92MI cells were able to specifically differentiate between peptide pulsed DIMT and 6268A BLCL, with a clear difference in cytotoxicity between the two different targets. FIG. 19B : CAR-mediated killing of peptide-pulsed DIMT BLCL could be blocked using the EBNA Clone 315 scFv-Fc fusion protein, but not by an irrelevant, isotype-matched scFv-Fc, at a 20:1 E:T ratio.
FIG. 20 shows the results of a 51 Cr release assay in which CAR-equipped NK92MI cells were cultured with 51 Cr labeled, unpulsed BLCLs. FIG. 20A : CAR-equipped NK92MI cells were more reactive towards the HLA-A2 + DIMT and JG19 BLCL versus the HLA-A2 − 6268A and GKO BLCL when cocultured in the absence of any exogenous peptide. FIG. 20B : CAR-mediated killing of unpulsed DIMT BLCL could be blocked using the EBNA Clone 315 scFv-Fc fusion protein but not by an irrelevant, isotype-matched scFv-Fc, at a 10:1 E:T ratio demonstrating that EBNA Clone 315 CAR-expressing NK92MI cells can specifically detect the HLA-A2-EBNA3C complex on HLA-A2 + BLCLs.
FIG. 21 shows the results of a 51 Cr release assay of EBNA in which CD16(V)-expressing NK92MI cells were cultured with 51 Cr labeled, LLDFVRFMGV- (SEQ ID NO: 4) pulsed DIMT BLCL and either EBNA Clone 315 or an irrelevant scFv-Fc. At an E:T ratio of 15:1, EBNA Clone 315 scFv-Fc was able to kill 30-35% of target cells.
FIG. 22 shows the results of a 51 Cr release assay of EBNA in which Clone 315 CAR-expressing NK92MI cells were cultured with LLDFVRFMGV (SEQ ID NO: 4) -pulsed DIMT BLCL as above and either EBNA Clone 315 or an irrelevant scFv-Fc. At the same E:T ratio as in FIG. 21 , the CAR-equipped cells were able to kill 80-90% of target cells, with specific inhibition using EBNA Clone scFv-Fc demonstrating that CAR-mediated killing is more potent than scFv-Fc-mediated ADCC on peptide-pulsed DIMT BLCL.
FIG. 23 shows the MSCV-based vector (top left panel) containing an IRES-GFP sequence along with ampicilin-resistance used for transduction and expression of anti-WT1 CAR in NK92MI cells. A. The WT1 Clone 45 scFv sequence was cloned into the CAR gene (anti-WT1 CAR) and further cloned into the MSCV-based vector. The resulting CAR (top right panel) is composed of the scFv and hinge region on the extracellular surface, a transmembrane domain, along with 4-1 BB and the CD3 chain present within the cell. B After retroviral packaging using 293T GP2 cells and transduction into NK92MI cells, approximately 27.5% of the NK92MI cells contained the construct based on GFP expression (bottom left panel; unfilled lines) when compared to mock transduced (empty retrovirus) NK92MI cells (bottom left panel; filled lines). Of the GFP-positive cells, the top 20% were flow cytometrically sorted and expanded to yield a population of stably transduced cells which were greater than 98% GFP positive (bottom right panel).
FIG. 24 shows the results of a 51 Cr release assay in which CAR-equipped NK92MI cells were able to specifically differentiate between peptide pulsed DIMT (▪) and 6268A BLCL (●), with a clear difference in cytotoxicity between the two different targets demonstrating that NK92MI cells expressing WT1 Clone 45 CAR can specifically detect the HLA-A2-RMFPNAPYL (SEQ ID NO: 1) complex on peptide-pulsed BLCLs.
FIG. 25 shows that CAR-mediated killing of peptide-pulsed DIMT BLCL could be blocked using a commercial anti-HLA-A2 antibody (5 μg/ml), but not by an irrelevant, isotype-matched antibody (5 μg/ml), at a 9:1 E:T ratio.
FIG. 26 shows that NK92MI cells expressing WT1 Clone 45 CAR can specifically detect the HLA-A2-RMFPNAPYL (SEQ ID NO: 1) complex on DIMT BLCL via 51 Cr release. FIG. 26A : CAR equipped NK92MI cells were able to specifically differentiate between DIMT and 6268A BLCL, with a clear difference in cytotoxicity between the two different targets. FIG. 26B CAR-mediated killing of DIMT BLCL could be blocked using the WT1 Clone 45 scFv-Fc fusion protein (20 μg/ml), but not by an irrelavent, isotype-matched scFv-Fc, at a 2:1 E:T ratio.
FIG. 27 shows that NK92MI cells expressing WT1 Clone 45 CAR can specifically detect the HLA-A2-RMFPNAPYL (SEQ ID NO: 1) complex on peptide-pulsed BLCLs via 51 Cr release. A CAR-equipped NK92MI cells were able to specifically differentiate between peptide pulsed DIMT and 6268A BLCL, with a clear difference in cytotoxicity between the two different targets.
FIG. 28 shows that NK92MI cells expressing WT1 Clone 45 CAR can specifically detect the HLA-A2-RMFPNAPYL (SEQ ID NO: 4) complex on 697 and OVCAR-3 cells via 51 Cr release.
DETAILED DESCRIPTION OF THE INVENTION
All patents, publications, applications and other references cited herein are hereby incorporated in their entirety into the present application.
In practicing the present invention, many conventional techniques in molecular biology, microbiology, cell biology, biochemistry, and immunology are used, which are within the skill of the art. These techniques are described in greater detail in, for example, Molecular Cloning: a Laboratory Manual 3 rd edition, J. F. Sambrook and D. W. Russell, ed. Cold Spring Harbor Laboratory Press 2001; Recombinant Antibodies for Immunotherapy, Melvyn Little, ed. Cambridge University Press 2009; “Oligonucleotide Synthesis” (M. J. Gait, ed., 1984); “Animal Cell Culture” (R. I. Freshney, ed., 1987); “Methods in Enzymology” (Academic Press, Inc.); “Current Protocols in Molecular Biology” (F. M. Ausubel et al., eds., 1987, and periodic updates); “PCR: The Polymerase Chain Reaction”, (Mullis et al., ed., 1994); “A Practical Guide to Molecular Cloning” (Perbal Bernard V., 1988); “Phage Display: A Laboratory Manual” (Barbas et al., 2001). The contents of these references and other references containing standard protocols, widely known to and relied upon by those of skill in the art, including manufacturers' instructions are hereby incorporated by reference as part of the present disclosure.
The following abbreviations are used throughout the application:
ADCC: Antibody-dependent cellular cytotoxicity
ALL: Acute lymphocytic leukemia
AML: Acute myeloid leukemia
APC: Antigen presenting cell
β2M: Beta-2-microglobulin
BiTE: Bi-specific T cell engaging antibody
BLCL: EBV-transformed B-cell lymphoblastic cell line
CAR: Chimeric antigen receptor
CDC: Complement dependent cytotoxicity
CMC: Complement mediated cytotoxicity
CDR: Complementarity determining region (see also HVR below)
C L : Constant domain of the light chain
CH 1 : 1 st constant domain of the heavy chain
CH 1, 2, 3 : 1 st , 2 nd and 3 rd constant domains of the heavy chain
CH 2, 3 : 2 nd and 3 rd constant domains of the heavy chain
CHO: Chinese hamster ovary
CTL: Cytotoxic T cell
EBNA3C: Epstein-Barr nucleur antigen 3C
EBV: Epstein-Barr virus
ECMV: Encephalomyocarditis virus
ER: Endoplasmic reticulum
E:T Ratio: Effector:Target ratio
Fab: Antibody binding fragment
FACS: Flow assisted cytometric cell sorting
FBS: Fetal bovine serum
GFP: Green fluorescence protein
HC: Heavy chain
HEL: Hen egg lysozyme
HLA: Human leukocyte antigen
HVR-H: Hypervariable region-heavy chain (see also CDR)
HVR-L: Hypervariable region-light chain
Ig: Immunoglobulin
IPTG: isopropyl-1-thio-β-D-galactopyranoside
IRES: Internal ribosome entry site
K D : Dissociation constant
k off : Dissociation rate
k on : Association rate
MHC: Major histocompatibility complex
OPD: O-phenylenediamine
PEG: Polyethylene glycol
scFv: Single-chain variable fragment
SPR: Surface plasmon resonance
TB: Terrific Broth
TCE: T cell epitope
TCR: T cell receptor
TIL: Tumor infiltrating lymphocyte
V H : Variable heavy chain
V L : Variable light chain
WT1: Wilms tumor protein 1
In the description that follows, certain conventions will be followed as regards the usage of terminology. Generally, terms used herein are intended to be interpreted consistently with the meaning of those terms as they are known to those of skill in the art.
An “antigen-binding protein” is a protein or polypeptide that comprises an antigen-binding region or antigen-binding portion, that is, has a strong affinity to another molecule to which it binds. Antigen-binding proteins encompass antibodies, antigen receptors and fusion proteins.
“Antibody” and “antibodies” as those terms are known in the art refer to antigen binding proteins that arise in the context of the immune system. The term “antibody” as referred to herein includes whole, full length antibodies and any fragment thereof in which the “antigen-binding portion” or “antigen-binding region” is retained or single chains thereof. A naturally occurring “antibody” is a glycoprotein comprising at least two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds. Each heavy chain is comprised of a heavy chain variable region (abbreviated herein as V H ) and a heavy chain constant region. The heavy chain constant region is comprised of three domains, CH1, CH2 and CH3. Each light chain is comprised of a light chain variable region (abbreviated herein as V L ) and a light chain constant region. The light chain constant region is comprised of one domain, C L . The V H and V L regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with regions that are more conserved, termed framework regions (FR). Each V H and V L is, composed of three CDRs and four FRs arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain a binding domain that interacts with an antigen. The constant regions of the antibodies may mediate the binding of the immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (C1q) of the classical complement system.
The term “antigen-binding portion” or “antigen-binding region” of an antibody (or simply “antigen portion”), as used herein, refers to that region or portion of the antibody that confers antigen specificity; fragments of antigen-binding proteins, for example, antibodies therefore, includes one or more fragments of an antibody that retain the ability to specifically bind to an antigen (e.g., an HLA-peptide complex). It has been shown that the antigen-binding function of an antibody can be performed by fragments of a full-length antibody. Examples of antigen-binding fragments encompassed within the term “antibody fragments” of an antibody include a Fab fragment, a monovalent fragment consisting of the V L , V H , C L and CH1 domains; a F(ab) 2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; a Fd fragment consisting of the V H and CH1 domains; a Fv fragment consisting of the V L and V H domains of a single arm of an antibody; a dAb fragment (Ward et al., 1989 Nature 341:544-546), which consists of a V H domain; and an isolated complementarity determining region (CDR).
Furthermore, although the two domains of the Fv fragment, V L and V H , are coded for by separate genes, they can be joined, using recombinant methods, by a synthetic linker that enables them to be made as a single protein chain in which the V L and V H regions pair to form monovalent molecules (known as single chain Fv (scFv); see e.g., Bird et al., 1988 Science 242:423-426; and Huston et al., 1988 Proc. Natl. Acad. Sci. 85:5879-5883). Such single chain antibodies are also intended to be encompassed within the term “antigen-binding portion” of an antibody. These antibody fragments are obtained using conventional techniques known to those of skill in the art, and the fragments are screened for utility in the same manner as are intact antibodies.
An “isolated antibody” or “isolated antigen-binding protein” is one which has been identified and separated and/or recovered from a component of its natural environment.
Traditionally, the MHC-peptide complex could only be recognized by a T-cell receptor (TCR), limiting our ability to detect an epitope of interest to use of T cell-based readout assays. In the present disclosure, antigen binding proteins, including antibodies and chimeric antigen receptors, having an antigen-binding region based on scFvs that are selected from human scFv phage display libraries using recombinant HLA-peptide complexes are described. These molecules demonstrated exquisite specificity, for example as shown with anti-EBNA and anti-WT1 antigen-binding proteins that recognize only the HLA-A2-LLDFVRFMGV (SEQ ID NO: 4) and HLA-A2-RMFPNAPYL (SEQ ID NO: 1) complexes, respectively. In addition, along with their inability to bind to HLA-complexes containing other peptides, the molecules were also unable to bind to the peptides themselves, further demonstrating their TCR-like specificity.
The scFvs of the disclosure selected by phage display were initially tested for their ability to bind to peptide presented on the surface of HLA-positive cells. After T2 cells and BLCLs were incubated in the presence of peptide, the cells could selectively recognize them using flow cytometry. In the case of one peptide, LLDFVRFMGV (SEQ ID NO: 4), the complex which the peptide formed with HLA could be detected on the surface of a BLCL even 24 hours after pulsing, further demonstrating the utility of these antibodies.
In some embodiments, the antigen binding proteins of the invention include antibodies that have the scFv sequence fused to the 2 nd and 3rd constant domains of the heavy chain (CH 2, 3 ), forming the bottom third of the Fc region of a human immunoglobulin to yield a bivalent protein and fragments thereof, increasing the overall avidity and stability of the antibody. In addition, the Fc portion allows the direct conjugation of other molecules, including but not limited to fluorescent dyes, cytotoxins, radioisotopes etc. to the antibody for example, for use in antigen quantitation studies, to immobilize the antibody for affinity measurements using surface plasmon resonance (SPR), for targeted delivery of a therapeutic agent, to test for Fc-mediated cytotoxicity using CD16-expressing immune effector cells and many other applications.
The purified scFv-Fc fusion proteins were tested for binding to their targeted T-cell epitopes (TCEs) by way of ELISA and peptide-pulsed APCs. Once they were validated to maintain their specificity, one molecule, EBNA Clone 315 was used for affinity determination. That this molecule was able to bind bound to its targeted TCE through a 1:1 interaction with 10-100 fold greater affinity compared to a typical TCR-MHC-peptide complex interaction was demonstrated.
Correlation of peptide pulsing of APCs with antigen density was demonstrated. Fluorescently-conjugated scFv-Fc, combined with quantitation beads, allowed the approximation of the number of complexes that are formed when cells are incubated with different concentrations of peptide. Using this information, it was possible to approximate the sensitivity of an scFv and scFv-Fc fusion protein to be around 100 complexes, using flow cytometry.
Lastly, whether the Fc portion of the fusion protein maintained its effector function was tested. Using a scFv embodiment of the invention, CD16(V)-transduced NK92MI cells, and peptide-pulsed target cells, it was demonstrated that the antibody maintained its Fc-mediated effector functions by way of ADCC.
The results presented here highlight the specificity, sensitivity and utility of the antigen binding proteins of the invention in targeting MHC-peptide complexes.
In one embodiment, therefore, the present invention relates to recombinant antigen-binding molecules and portions thereof that recognize a complex of a peptide/protein fragment derived from an intracellular or viral protein, and an MHC class I molecule, for example, as the complex might be appear at the cell surface for recognition by a T-cell.
The molecules of the invention are based on the identification and selection of a single chain variable fragment (scFv) using phage display, the amino acid sequence of which confers the molecules' specificity for the MHC restricted peptide of interest and forms the basis of all antigen binding proteins of the disclosure. The scFv, therefore, can be used to design a diverse array of “antibody” molecules, including, for example, full length antibodies, fragments thereof, such as Fab and F(ab′) 2 , minibodies, fusion proteins, including scFv-Fc fusions, multivalent antibodies, that is, antibodies that have more than one specificity for the same antigen or different antigens, for example, bispecific T-cell engaging antibodies (BiTe), tribodies, etc. (see Cuesta et al., Multivalent antibodies: when design surpasses evolution. Trends in Biotechnology 28:355-362 2010).
In an embodiment in which the antigen-binding protein is a full length antibody, the heavy and light chains of an antibody of the invention may be full-length (e.g., an antibody can include at least one, and preferably two, complete heavy chains, and at least one, and preferably two, complete light chains) or may include an antigen-binding portion (a Fab, F(ab′)2, Fv or a single chain Fv fragment (“scFv”)). In other embodiments, the antibody heavy chain constant region is chosen from, e.g., IgG1, IgG2, IgG3, IgG4, IgM, IgA1, IgA2, IgD, and IgE. In some embodiments, the immunoglobulin isotype is selected from IgG1, IgG2, IgG3, and IgG4, more particularly, IgG1 (e.g., human IgG1). The choice of antibody type will depend on the immune effector function that the antibody is designed to elicit.
In constructing a recombinant immunoglobulin, appropriate amino acid sequences for constant regions of various immunoglobulin isotypes and methods for the production of a wide array of antibodies are well known to those of skill in the art.
In some embodiments, the constant region of the antibody is altered, e.g., mutated, to modify the properties of the antibody (e.g., to increase or decrease one or more of: Fc receptor binding, antibody carbohydrate, for example glycosylation or fucosylation, the number of cysteine residues, effector cell function, or complement function).
In one embodiment, the antigen binding protein is an anti-WT1/HLA-A2 antibody or fragment thereof having an antigen binding region that comprises the amino acid sequence of SEQ ID NO: 2 and specifically binds to a peptide with the amino acid sequence RMFPNAPYL (SEQ ID NO: 1) in conjunction with HLA-A2. In other embodiments, the anti-WT-1 antibody is a scFv-Fc fusion protein or full length human IgG with VH and VL regions or CDRs selected from Table 1.
TABLE 1
Antigen
WT1
Peptide
RMFPNAPYL (SEQ ID NO: 1)
CDRs:
1
2
3
VH
SYAMS
QIDPWGQET
LTGRFDY
(SEQ ID
LYADSVKG
(SEQ ID
NO. 38)
(SEQ ID
NO. 48)
NO. 40)
VL
RASQSISSYLN
SASQLQS
QQGPGTPNT
(SEQ ID
(SEQ ID
(SEQ ID
NO: 56)
NO: 57)
NO. 64)
Full VH
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP
GKGLEWVSQIDPWGQETLYADSVKGRFTISRDNSKNTLYLQ
MNSLRAEDTAVYYCAKLTGRFDYWGQGTLVTVS
(SEQ ID NO: 22)
Full VL
STDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQK
PGKAPKLLIYSASQLQSGVPSRFSGSGSGTDFTLTISSLQP
EDFATYYCQQGPGTPNTFGQGTKVEIKRA
(SEQ ID NO: 23)
scFv
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP
clone
GKGLEWVSQIDPWGQETLYADSVKGRFTISRDNSKNTLYLQ
45
MNSLRAEDTAVYYCAKLTGRFDYWGQGTLVTVSSGGGGSGG
GGSGGGGSTDIQMTQSPSSLSASVGDRVTITCRASQSISSY
LNWYQQKPGKAPKLLIYSASQLQSGVPSRFSGSGSGTDFTL
TISSLQPEDFATYYCQQGPGTPNTFGQGTKVEIKRA
(SEQ ID NO: 2)
DNA
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCC
(5′-3′)
TGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCA
CCTTTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGCTCCA
GGGAAGGGGCTGGAGTGGGTCTCACAGATTGATCCTTGGGG
TCAGGAGACATTGTACGCAGACTCCGTGAAGGGCCGGTTCA
CCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAA
ATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTG
TGCGAAACTTACTGGTCGGTTTGACTACTGGGGCCAGGGAA
CCCTGGTCACCGTCTCAAGCGGTGGAGGCGGTTCAGGCGGA
GGTGGCAGCGGCGGTGGCGGGTCGACGGACATCCAGATGAC
CCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAG
TCACCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTAT
TTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCT
CCTGATCTATTCGGCATCCCAGTTGCAAAGTGGGGTCCCAT
CAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTC
ACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTACTA
CTGTCAACAGGGTCCGGGGACTCCTAATACGTTCGGCCAAG
GGACCAAGGTGGAAATCAAACGGGCC
(SEQ ID NO: 3)
In another embodiment, the antigen binding protein is an anti-EBNA3C antibody or fragment thereof that has an antigen binding region that comprises the amino acid sequence of SEQ ID NO: 5 and specifically binds to a peptide with the amino acid sequence LLDFVRFMGV (SEQ ID NO: 4) in conjunction with HLA-A2. In other embodiments, the anti-EBNA3C antibody is a scFv-Fc fusion protein or full length human IgG with VH and VL regions or CDRs selected from Table 2.
TABLE 2
Antigen
EBNA3C
Peptide
LLDFVRFMGV (SEQ ID NO: 4
CDRs
1
2
3
VH
GYAMS
EIAPPGLNT
SDTAFDY
(SEQ ID
RYADSVKG
(SEQ ID
NO: 39)
(SEQ ID
NO: 49)
NO: 41)
VL
RASQSISSYLN
LASNLQS
QQAEYMPLT
(SEQ ID
(SEQ ID
(SEQ ID
NO: 56)
NO: 58)
NO: 65)
Full VH
EVQLLESGGGLVQPGGSLRLSCAASGFTFSGYAMSWVRQAPG
KGLEWVSEIAPPGLNTRYADSVKGRFTISRDNSKNTLYLQMN
SLRAEDTAVYYCAKSDTAFDYWGQGTLVTVS
(SEQ ID NO: 24)
Full VL
STDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKP
GKAPKLLIYLASNLQSGVPSRFSGSGSGTDFTLTISSLQPED
FATYYCQQAEYMPLTFGQGTKVEIKRA
(SEQ ID NO: 25 )
scFv
EVQLLESGGGLVQPGGSLRLSCAASGFTFSGYAMSWVRQAPG
clone
KGLEWVSEIAPPGLNTRYADSVKGRFTISRDNSKNTLYLQMN
315
SLRAEDTAVYYCAKSDTAFDYWGQGTLVTVSSGGGGSGGGGS
GGGGSTDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWY
QQKPGKAPKLLIYLASNLQSGVPSRFSGSGSGTDFTLTISSL
QPEDFATYYCQQAEYMPLTFGQGTKVEIKRA
(SEQ ID NO: 5)
DNA
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCT
(5′-3′)
GGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACC
TTTAGCGGCTATGCCATGAGCTGGGTCCGCCAGGCTCCAGGG
AAGGGGCTGGAGTGGGTCTCAGAGATTGCGCCGCCTGGTTTG
AATACACGTTACGCAGACTCCGTGAAGGGCCGGTTCACTATC
TCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAAC
AGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAAA
TCGGATACTGCTTTTGACTACTGGGGCCAGGGAACCCTGGTC
ACCGTCTCGAGCGGTGGAGGCGGTTCAGGCGGAGGTGGCAGC
GGCGGTGGCGGGTCGACGGACATCCAGATGACCCAGTCTCCA
TCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACT
TGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTAT
CAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCTG
GCATCCAATTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGC
AGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTG
CAACCTGAAGATTTTGCAACTTACTACTGTCAACAGGCGGAG
TATATGCCTCTGACGTTCGGCCAAGGGACCAAGGTGGAAATC
AAACGGGCC
(SEQ ID NO: 6)
In yet another embodiment, the antigen binding protein is an anti-CCND1 antibody or fragment thereof that comprises the amino acid sequence of one of SEQ ID NOs: 8 or 10 and specifically binds to a peptide with the amino acids sequence RLTRFLSRV (SEQ ID NO: 7) in conjunction with HLA-A2. In other embodiments, the anti-CCND1 antibody is a scFv-Fc fusion or full length human IgG with VH and VL regions or CDRs selected from Tables 3 and 4.
TABLE 3
Antigen
CCND1
Peptide
RLTRFLSRV (SEQ ID NO. 7)
CDRs
1
2
3
VH
SYAMS
TISDSDATDY
TTDYFDY
(SEQ ID
ADSVKG(SEQ ID
(SEQ ID
NO:38)
NO: 42)
NO: 50)
VL
RASQSIS
YASYLQS
QQSSSSPDT
SYLN (SEQ ID
(SEQ ID
(SEQ ID
NO: 56)
NO: 59)
NO: 66)
Full VH
EVQLLESGGGLVQPGGSLRLSCATSGFTFSSYAMSWVRQAPGK
GLEWVSTISDSDATDYADSVKGRFTISRDNSKNTLYLQMNSLR
AEDTAVYYCAKTTDYFDYWGQGTLVTVS (SEQ ID NO: 26)
Full VL
STDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPG
KAPKLLIYYASYLQSGVPSRFSGSGSGTDFTLTISSLCIPEDF
ATYYCQQSSSSPDTFGQGTKVEIKRAA (SEQ ID NO: 27)
scFv
EVQLLESGGGLVQPGGSLRLSCATSGFTFSSYAMSWVRQAPGK
clone 5,
GLEWVSTISDSDATDYADSVKGRFTISRDNSKNTLYLQMNSLR
17
AEDTAVYYCAKTTDYFDYWGQGTLVTVSSGGGGSGGGGSGGGG
STDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPG
KAPKLLIYYASYLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCQQSSSSPDTFGQGTKVEIKRAA (SEQ ID NO: 8)
DNA
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTG
(5′-3′)
GGGGGTCCCTGAGACTCTCCTGTGCAACCTCTGGATTCACCTT
TAGCAGCTATGCCATGAGCTGGGTCCGCCAGGCTCCAGGGAAG
GGGCTGGAGTGGGTCTCAACTATTTCTGATAGTGATGCTACAG
ATTACGCAGACTCCGTGAAGGGCAGGTTCACCATCTCCAGAGA
CAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGA
GCCGAGGACACGGCCGTATATTACTGTGCGAAAACTACTGATT
ATTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCGAG
CGGTGGAGGCGGTTCAGGCGGAGGTGGCAGCGGCGGTGGCGGG
TCGACGGACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTG
CATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCA
GAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAACCAGGG
AAAGCCCCTAAGCTCCTGATCTATTATGCATCCTATTTGCAAA
GTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGA
TTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCA
ACTTACTACTGTCAACAGTCTTCTAGTTCTCCTGATACGTTCG
GCCAAGGGACCAAGGTGGAAATCAAACGGGCGGCC
(SEQ ID NO: 9)
TABLE 4
Antigen
CCND1
Peptide
RLTRFLSRV (SEQ ID NO: 7)
CDRs:
1
2
3
VH
SYAMS
DISDDGDATYY
SSTTFDY
(SEQ ID
ADSVKG (SEQ ID
(SEQ ID
NO: 38)
NO: 43)
NO: 51)
VL
RASQSISS
AASALQS
QQGTDSPAT
YLN (SEQ ID
(SEQ ID
(SEQ ID
NO: 56)
NO: 60)
NO: 67)
Full VH
EVCILLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP
GKGLEWVSDISDDGDATYYADSVKGRFTISRDNSKNTLYLQM
NSLRAEDTAVYYCAKSSTTFDYWGQGTLVTVS
(SEQ ID NO: 28)
Full VL
STDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKP
GKAPKLLIYAASALQSGVPSRFSGSGSGTDFTLTISSLQPED
FATYYCQQGTDSPATFGQGTKVEIKRAA (SEQ ID NO: 29)
scFv
EVCILLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAP
clone
GKGLEWVSDISDDGDATYYADSVKGRFTISRDNSKNTLYLQM
43
NSLRAEDTAVYYCAKSSTTFDYWGQGTLVTVSSGGGGSGGGG
SGGGGSTDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNW
YQQKPGKAPKLLIYAASALQSGVPSRFSGSGSGTDFTLTISS
LQPEDFATYYCQQGTDSPATFGQGTKVEIKRAA
(SEQ ID NO: 10)
DNA
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCT
(5′-3′)
GGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACC
TTTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGCTCCAGGG
AAGGGGCTGGAGTGGGTCTCAGATATTTCTGATGATGGTGAT
GCTACATATTACGCAGACTCCGTGAAGGGCAGGTTCACCATC
TCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAAC
AGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAAA
TCTTCTACTACTTTTGACTACTGGGGCCAGGGAACCCTGGTC
ACCGTCTCGAGCGGTGGAGGCGGTTCAGGCGGAGGTGGCAGC
GGCGGTGGCGGGTCGACGGACATCCAGATGACCCAGTCTCCA
TCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACT
TGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTAT
CAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCT
GCATCCGCCTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGC
AGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTG
CAACCTGAAGATTTTGCAACTTACTACTGTCAACAGGGTACT
GATAGTCCTGCTACGTTCGGCCAAGGGACCAAGGTGGAAATC
AAACGGGCGGCC (SEQ ID NO: 11)
In yet another embodiment, the antigen binding protein is an anti-HUD antibody or fragment thereof that comprises the amino acid sequence of one of SEQ ID NOs: 13, 14 and 17 and has an antigen-binding region that specifically binds to a peptide with the amino acid sequence RIITSTILV (SEQ ID NO: 12) in conjunction with HLA-A2. In other embodiments, the anti-HUD antibody is a scFv-Fc fusion protein or full length human IgG with VH and VL regions or CDRs selected from Tables 5-7.
TABLE 5
Antigen
HUD
Peptide
RIITSTILV (SEQ ID NO: 12)
CDRs:
1
2
3
VH
SYAMS
DIASTGYYTDY
NNASFDY
(SEQ ID
ADSVKG (SEQ ID
(SEQ ID
NO: 38)
NO: 44)
NO: 52)
VL
RASQSISS
DASTLQS
QQTDSYP
YLN (SEQ ID
(SEQ ID
TT (SEQ ID
NO: 56)
NO: 61)
NO: 68)
Full VH
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQA
PGKGLEWVSDIASTGYYTDYADSVKGRFTISRDNSKNTLY
LQMNSLRAEDTAVYYCAKNNASFDYWGQGTLVTVS
(SEQ ID NO: 30)
Full VL
STDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQ
KPGKAPKLLIYDASTLQSGVPSRFSGSGSGTDFTLTISSL
QPEDFATYYCQQTDSYPTTFGQGTKVEIKR
(SEQ ID NO: 31)
scFv
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQA
clone
PGKGLEWVSDIASTGYYTDYADSVKGRFTISRDNSKNTLY
H128
LQMNSLRAEDTAVYYCAKNNASFDYWGQGTLVTVSSGGGG
SGGGGSGGGGSTDIQMTQSPSSLSASVGDRVTITCRASQS
ISSYLNWYQQKPGKAPKLLIYDASTLQSGVPSRFSGSGSG
TDFTLTISSLQPEDFATYYCQQTDSYPTTFGQGTKVEIKR
(SEQ ID NO: 13)
DNA
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGC
(5′-3′)
CTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATT
CACCTTTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGCT
CCAGGGAAGGGGCTGGAGTGGGTCTCGGATATTGCTTCTA
CTGGTTATTATACAGATTACGCAGACTCCGTGAAGGGCCG
GTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTAT
ATTACTGTGCGAAAAATAATGCTAGTTTTGACTACTGGGG
CCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGT
TCAGGCGGAGGTGGCAGCGGCGGTGGCGGGTCGACGGACA
TCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGT
AGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGC
ATTAGCAGCTATTTAAATTGGTATCAGCAGAAACCAGGGA
AAGCCCCTAAGCTCCTGATCTATGATGCATCCACTTTGCA
AAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGG
ACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAG
ATTTTGCAACTTACTACTGTCAACAGACTGATTCTTATCC
TACTACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGG
(SEQ ID NO: 15)
TABLE 6
Antigen
HUD
Peptide
RIITSTILV (SEQ ID NO: 12)
CDRs:
1
2
3
VH
SYAMS
SISSSGYYTD
SASSFDY
(SEQ ID
YADSVKG (SEQ ID
(SEQ ID
NO: 38)
NO: 45)
NO: 53)
VL
RASQSIS
DASTLQS
QQDDAYP
SYLN (SEQ ID
(SEQ ID
TT (SEQ ID
NO: 56)
NO: 61)
NO: 69)
Full VH
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQA
PGKGLEWVSSISSSGSYTDYADSVKGRFTISRDNSKNTLY
LQMNSLRAEDTAVYYCAKSASSFDYWGQGTLVTVS
(SEQ ID NO: 32)
Full VL
STDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQ
KPGKAPKLLIYDASTLQSGVPSRFSGSGSGTDFTLTISSL
QPEDFATYYCQQDDAYPTTFGQGTKVEIKR
(SEQ ID NO: 33)
scFv
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQA
clone
PGKGLEWVSSISSSGSYTDYADSVKGRFTISRDNSKNTLY
H78
LQMNSLRAEDTAVYYCAKSASSFDYWGQGTLVTVSSGGGG
SGGGGSGGGGSTDIQMTQSPSSLSASVGDRVTITCRASQS
ISSYLNWYQQKPGKAPKLLIYDASTLQSGVPSRFSGSGSG
TDFTLTISSLQPEDFATYYCQQDDAYPTTFGQGTKVEIKR
(SEQ ID NO: 14)
DNA
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGC
(5′-3′)
CTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATT
CACCTTTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGCT
CCAGGGAAGGGGCTGGAGTGGGTCTCATCTATTAGTAGTT
CTGGTAGTTATACAGATTACGCAGACTCCGTGAAGGGCCG
GTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTAT
ATTACTGTGCGAAATCTGCTTCTTCTTTTGACTACTGGGG
CCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGT
TCAGGCGGAGGTGGCAGCGGCGGTGGCGGGTCGACGGACA
TCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGT
AGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGC
ATTAGCAGCTATTTAAATTGGTATCAGCAGAAACCAGGGA
AAGCCCCTAAGCTCCTGATCTATGATGCATCCACTTTGCA
AAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGG
ACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAG
ATTTTGCAACTTACTACTGTCAACAGGATGATGCTTATCC
TACTACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGG
(SEQ ID NO: 16)
TABLE 7
Antigen
HUD
Peptide
RIITSTILV (SEQ ID NO: 12)
CDRs:
1
2
3
VH
SYAMS
SISSDGSYTDY
STDAFDY
(SEQ ID
ADSVKG (SEQ ID
(SEQ ID
NO: 38)
NO: 46)
NO: 54)
VL
RASQSISS
AASYLQS
QQDNNY
YLN (SEQ ID
(SEQ ID
PTT (SEQ ID
NO: 56)
NO: 62)
NO: 70)
Full VH
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQA
PGKGLEWVSSISSDGSYTDYADSVKGRFTISRDNSKNTLY
LQMNSLRAEDTAVYYCAKSTDAFDYWGQGTLVTVS
(SEQ ID NO: 34)
Full VL
STDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQ
KPGKAPKLLIYAASYLQSGVPSRFSGSGSGTDFSLTISSL
QPEDFATYYCQQDNNYPTTFGQGTKVEIKR
(SEQ ID NO: 35)
scFv
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQA
clone
PGKGLEWVSSISSDGSYTDYADSVKGRFTISRDNSKNTLY
H110
LQMNSLRAEDTAVYYCAKSTDAFDYWGQGTLVTVSSGGGG
SGGGGSGGGGSTDIQMTQSPSSLSASVGDRVTITCRASQS
ISSYLNWYQQKPGKAPKLLIYAASYLQSGVPSRFSGSGSG
TDFSLTISSLQPEDFATYYCQQDNNYPTTFGQGTKVEIKR
(SEQ ID NO: 17)
DNA
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGC
(5′-3′)
CTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATT
CACCTTTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGCT
CCAGGGAAGGGGCTGGAGTGGGTCTCAAGTATTTCTTCTG
ATGGTAGTTATACAGATTACGCAGACTCCGTGAAGGGCCG
GTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTAT
CTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTAT
ATTACTGTGCGAAATCTACTGATGCTTTTGACTACTGGGG
CCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGT
TCAGGCGGAGGTGGCAGCGGCGGTGGCGGGTCGACGGACA
TCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGT
AGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGC
ATTAGCAGCTATTTAAATTGGTATCAGCAGAAACCAGGGA
AAGCCCCTAAGCTCCTGATCTATGCTGCATCCTATTTGCA
AAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGG
ACAGATTTCTCTCTCACCATCAGCAGTCTGCAACCTGAAG
ATTTTGCAACTTACTACTGTCAACAGGATAATAATTATCC
TACTACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGG
(SEQ ID NO: 18)
In yet another embodiment, the antigen binding protein is an anti-cdr2 antibody or fragment thereof that comprises the amino acid sequence of SEQ ID NO: 20 and specifically binds to a peptide with amino acids LLEEMFLTV (SEQ ID NO: 19) in conjunction with HLA-A2. In other embodiments, the anti-cdr2 antibody is a scFv-Fc fusion protein or full length human IgG with VH and VL regions or CDRs selected from Table 8.
TABLE 8
Antigen
cdr2
Peptide
LLEEMFLTV(SEQ ID NO: 19)
CDRs:
1
2
3
VH
SYAMS
TINYSGSGTTY
NAAYFDY
(SEQ ID
ADSVKG(SEQ ID
(SEQ ID
NO: 38)
NO: 47)
NO: 55)
VL
RASQSIS
GASGLQS
QQSANAP
SYLN(SEQ ID
(SEQ ID
TT(SEQ ID
NO: 56)
NO: 63)
NO: 71)
Full VH
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPG
KGLEWVSTINYSGSGTTYADSVKGRFTISRDNSKNTLYLQMN
SLRAEDTAVYYCAKNAAYFDYWGQGTLVTVS
(SEQ ID NO: 36)
Full VL
STDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKP
GKAPKLLIYGASGLQSGVPSRFSGSGSGTDFTLTISSLQPED
FATYYCQQSANAPTTFGQGTKVEIKR(SEQ ID NO: 37)
scFv
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPG
clone
KGLEWVSTINYSGSGTTYADSVKGRFTISRDNSKNTLYLQMN
L9
SLRAEDTAVYYCAKNAAYFDYWGQGTLVTVSSGGGGSGGGGS
GGGGSTDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWY
QQKPGKAPKLLIYGASGLQSGVPSRFSGSGSGTDFTLTISSL
QPEDFATYYCQQSANAPTTFGQGTKVEIKR
(SEQ ID NO: 20)
DNA
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCT
(5′-3′)
GGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACC
TTTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGCTCCAGGG
AAGGGGCTGGAGTGGGTCTCAACTATTAATTATTCTGGTTCT
GGTACAACTTACGCAGACTCCGTGAAGGGCAGGTTCACCATC
TCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAAC
AGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAAA
AATGCTGCTTATTTTGACTACTGGGGCCAGGGAACCCTGGTC
ACCGTCTCGAGCGGTGGAGGCGGTTCAGGCGGAGGTGGCAGC
GGCGGTGGCGGGTCGACGGACATCCAGATGACCCAGTCTCCA
TCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACT
TGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTAT
CAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGGT
GCATCCGGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGC
AGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTG
CAACCTGAAGATTTTGCAACTTACTACTGTCAACAGTCTGCT
AATGCTCCTACTACGTTCGGCCAAGGGACCAAGGTGGAAATC
AAACGG(SEQ ID NO: 21)
Embodiments of the antigen-binding proteins of the disclosure in accordance with Tables 1-8 include, but are not limited to the following:
an anti-WT-1 antibody which binds to an HLA-restricted peptide RMFPNAPYL (SEQ ID NO: 1) comprising: (i) an HVR-L1 sequence of RASQSISSYLN (SEQ ID NO: 56) (ii) an HVR-L2 sequence of SASQLQS (SEQ ID NO: 57) (iii) an HVR-L3 sequence of QQGPGTPNT (SEQ ID NO: 64) (iv) an HVR-H1 sequence of SYAMS (SEQ ID NO: 38) (v) an HVR-H2 sequence of QIDPWGQETLYADSVKG (SEQ ID NO: 40), and (vi) an HVR-H3 sequence of LTGRFDY (SEQ ID NO: 48);
an anti-EBNA3C antibody which binds to HLA-A2 restricted peptide LLDFVRFMGV (SEQ ID NO: 4) comprising: (i) an HVR-L1 sequence of RASQSISSYLN (SEQ ID NO: 56) (ii) an HVR-L2 sequence of LASNLQS (SEQ ID NO: 58) (iii) an HVR-L3 sequence of QQAEYMPLT (SEQ ID NO: 65) (iv) an HVR-H1 sequence of GYAMS (SEQ ID NO: 39) (v) an HVR-H2 sequence of EIAPPGLNTRYADSVKG (SEQ ID NO: 41), and (vi) an HVR-H3 sequence of SDTAFDY (SEQ ID NO: 49);
an anti-CCND1 antibody which binds to HLA-A2 restricted peptide RLTRFLSRV (SEQ ID NO: 7) comprising: (i) an HVR-L1 sequence of RASQSISSYLN (SEQ ID NO: 56) (ii) an HVR-L2 sequence of YASYLQS (SEQ ID NO: 59) (iii) an HVR-L3 sequence of QQSSSSPDT (SEQ ID NO: 66) (iv) an HVR-H1 sequence of SYAMS (SEQ ID NO: 38) (v) an HVR-H2 sequence of TISDSDATDYADSVKG (SEQ ID NO: 42), and (vi) an HVR-H3 sequence of TTDYFDY (SEQ ID NO: 50);
an anti-CCND1 antibody which binds to HLA-A2 restricted peptide RLTRFLSRV (SEQ ID NO: 7) comprising: (i) an HVR-L1 sequence of RASQSISSYLN (SEQ ID NO: 56) (ii) an HVR-L2 sequence of AASALQS (SEQ ID NO: 60) (iii) an HVR-L3 sequence of QQGTDSPAT (SEQ ID NO: 67) (iv) an HVR-H1 sequence of SYAMS (SEQ ID NO: 38) (v) an HVR-H2 sequence of DISDDGDATYYADSVKG (SEQ ID NO: 43), and (vi) an HVR-H3 sequence of SSTTFDY (SEQ ID NO: 51);
an anti-HUD antibody which binds to HLA-A2 restricted peptide RIITSTILV (SEQ ID NO: 12) comprising: (i) an HVR-L1 sequence of RASQSISSYLN (SEQ ID NO: 56) (ii) an HVR-L2 sequence of DASTLQS (SEQ ID NO: 61) (iii) an HVR-L3 sequence of QQTDSYPTT (SEQ ID NO: 68) (iv) an HVR-H1 sequence of SYAMS (SEQ ID NO: 38) (v) an HVR-H2 sequence of DIASTGYYTDYADSVKG (SEQ ID NO: 44), and (vi) an HVR-H3 sequence of NNASFDY (SEQ ID NO: 52);
an anti-HUD antibody which binds to HLA-A2 restricted peptide RIITSTILV (SEQ ID NO: 12) comprising: (i) an HVR-L1 sequence of RASQSISSYLN (SEQ ID NO: 56) (ii) an HVR-L2 sequence of DASTLQS (SEQ ID NO: 61) (iii) an HVR-L3 sequence of QQDDAYPTT (SEQ ID NO: 69) (iv) an HVR-H1 sequence of SYAMS (SEQ ID NO: 38) (v) an HVR-H2 sequence of SISSSGYYTDYADSVKG (SEQ ID NO: 45), and (vi) an HVR-H3 sequence of SASSFDY (SEQ ID NO: 53);
an anti-HUD antibody which binds to HLA-A2 restricted peptide RIITSTILV (SEQ ID NO: 12) comprising: (i) an HVR-L1 sequence of RASQSISSYLN (SEQ ID NO: 56) (ii) an HVR-L2 sequence of AASYLQS (SEQ ID NO: 62) (iii) an HVR-L3 sequence of QQDNNYPTT (SEQ ID NO: 70) (iv) an HVR-H1 sequence of SYAMS (SEQ ID NO: 38) (v) an HVR-H2 sequence of SISSDGSYTDYADSVKG (SEQ ID NO: 46), and (vi) an HVR-H3 sequence of STDAFDY (SEQ ID NO: 54); and
an anti-cdr2 antibody which binds to HLA-A2 restricted peptide LLEEMFLTV (SEQ ID NO: 19) comprising: (i) an HVR-L1 sequence of RASQSISSYLN (SEQ ID NO: 56) (ii) an HVR-L2 sequence of GASGLQS (SEQ ID NO: 63) (iii) an HVR-L3 sequence of QQSANAPTT (SEQ ID NO: 71) (iv) an HVR-H1 sequence of SYAMS (SEQ ID NO: 38) (v) an HVR-H2 sequence of TINYSGSGTTYADSVKG (SEQ ID NO: 47), and (vi) an HVR-H3 sequence of NAAYFDY (SEQ ID NO: 55).
EXAMPLES
General Procedures
Example 1
Production of Biotinylated MHC-Peptide Complexes
Soluble MHC class I/peptide complexes were generated by overexpression of the HLA-A2 heavy chain (HC) and β2 microglobulin (β 2 M) as recombinant proteins in E. coli and subsequent in vitro refolding and assembly in the presence of high concentrations of specific peptide (35, 36). To obtain soluble MHC/peptide complexes the HC sequence was mutagenized to remove the cytosolic and transmembrane regions. In order to specifically biotinylate refolded, monomeric MHC/peptide complexes, the HC was expressed as a fusion protein containing a specific biotinylation site at the C-terminus (37, 38). These short sequences are sufficient for enzymatic in vitro biotinylation of a single lysine residue within this sequence using the biotin protein ligase BirA (39). This procedure was carried out by the MSKCC Tetramer Core Facility.
Example 2
Selection of Phage on Biotinylated MHC-Peptide Complexes
Ex. 2.1
Selection of Phage on HLA-A2/EBNA3C (EBNA) Complex
The Tomlinson I+J human scFv phage display libraries (40), containing approximately 2.85×10 8 independent scFv clones, were used for selection according to previously published methods (22) with modifications. 7.5×10 12 Phage, from the combination of both libraries, were first preincubated with streptavidin paramagnetic DYNABEADS (30 μl; Dynal, Oslo, Norway) and 150 μg unbiotinylated HLA-A2-YVDPVITSI (SEQ ID NO: 75) (irrelevant complex) in 1 ml of PBS to remove any phage which expressed an antibody that binds to streptavidin or the general framework of HLA-A2.
The DYNABEADS were subsequently captured using a magnet and the supernatant (phage and irrelevant complex mixture) transferred to a separate tube containing 7.5 μg of biotinylated HLA-A2-LLDFVRFMGV (SEQ ID NO: 4) (Epstein-Barr virus EBNA3C-derived) and 7.5 μg of biotinylated HLA-A2-NLVPMVATV (SEQ ID NO: 73) (Cytomedullovirus pp65-derived) and incubated at RT for 1 hour. The final mixture (1 ml) was then added to 200 μl of DYNABEADS (preincubated with 2% Milk and washed with PBS) and the contents were mixed for 15 min. at RT with continuous rotation. The beads were then washed 10 times with PBS/0.1% TWEEN and 3 times with PBS and the bound phage were eluted from the DYNABEADS using 1 mg/ml trypsin in PBS (0.5 ml) for 15 min. at RT.
The phage were then used to infect TG1 E. coli (growing in log phase) at 37° C. in 20 ml of LB for 1 hour. 10 12 KM13 helper phage was subsequently added to the mixture, further incubated for an additional 30 minutes, and the cells pelleted using centrifugation (3000 rpm for 10 min.). The resulting cell pellet was resuspended in 200 ml LB+Ampicillin (100 μg/ml)+Kanamycin (50 μg/ml) and incubated overnight at 30° C.
The following morning, the overnight cultures were centrifuged at 3000 rpm for 15 min. and the supernatant (180 ml) was mixed with polyethylene glycol (PEG) on ice for 1 hour so as to precipitate the amplified phage from the previous round of selection. The PEG/phage mixture was then centrifuged at 3000 rpm for 20 min., and some of the resulting phage pellet used for subsequent rounds of panning while the rest was frozen down in 15% glycerol at −80° C. Subsequent rounds of panning were done using the same protocol as above with an increase in DYNABEADS washing steps and a decrease in the amount of biotinylated complexes used for selection.
After the final round of antibody selection (3 rd or 4th round), the eluted phage were used to infect both TG1 and HB2151 E. coli ; TG1 cells were cultured overnight as mentioned above while the HB2151 cells were plated on TYE+Ampicillin (100 μg/ml) agar plates. The next morning, individual colonies from the agar plate were picked and used to inoculate individual wells of a 48-well plate containing 400 μl LB+Ampicillin (100 μg/ml)/well. After incubation for 3-6 hours at 37° C., 200 μl of 50% glycerol solution was added to each well and the plates stored at −80° C. as monoclonal stock cultures.
Ex. 2.2
Selection of Phage on HLA-A2-RMFPNAPYL (SEQ ID NO: 1) (WT-1) Complex
Selection was done similarly to the method above with slight modifications. 3.7×10 12 Phage from the combination of both libraries, were first preincubated with streptavidin paramagnetic DYNABEADS (50 μl; Dynal, Oslo, Norway) and 20 μg unbiotinylated HLA-A2-NLVPMVATV (SEQ ID NO: 73) (irrelevant complex) in 1 ml of PBS to deplete the streptavidin and HLA-A2 binders. The DYNABEADS were subsequently captured using a magnet and the supernatant (phage and irrelevant complex mixture) transferred to a separate tube containing 5 μg of biotinylated HLA-A2-RMFPNAPYL (SEQ ID NO: 1) (WT1-derived) and incubated at RT for 1 hour. The final mixture (1 ml) was then added to 100 μl of DYNABEADS (preincubated with 2% Milk and washed with PBS) and the contents were mixed for 30 min. at RT with continuous rotation. The beads were then washed 10 times with PBS/0.1% TWEEN and 3 times with PBS and the bound phage were eluted from the DYNABEADS using 1 mg/ml trypsin in PBS (0.5 ml) for 20 min. at RT. All subsequent steps were performed as above.
Example 3
Expression and Purification of Soluble scFv from HB2151
Using the monoclonal glycerol stocks containing individual HB2151 clones, separate 48-well plates containing 400 μl LB+Ampicillin (100 μg/ml)/well were inoculated in a replica-plate type format using sterile pipette tips. The 48-well culture plates were subsequently incubated at 37° C. until the majority of the wells reached an OD600 of 0.4. 200 μl LB+Ampicillin (100 μg/ml)+isopropyl-1-thio-β-D-galactopyranoside (IPTG; 1 mM final concentration) was subsequently added to each well to induce scFv production and the plates were further incubated overnight at 28° C. The next morning, the plates were centrifuged at 3000 rpm for 15 min. and the supernatant used for scFv screening.
For large scale expression and purification, monoclonal glycerol stocks were used to inoculate 3 ml of Terrific Broth (TB) and incubated at 37° C. until an OD600 of 0.8 was reached. Each 3 ml culture was subsequently divided amongst four flasks, each containing 250 ml TB+Ampicillin (100 μg/ml). The cultures were then incubated at 37° C. until an OD600 of 0.4-0.5 was reach, after which IPTG was added to a final concentration of 0.5 mM and the cultures incubated overnight at 30° C. The next morning, the overnight cultures were centrifuged at 4000 rpm for 25 min. The supernatant was discarded and the pellets dissolved in 50 ml PBS+10 mM imidazole. The cell suspensions were passed through a cell homogenizer (5000 pounds per square inch) and the resulting cell lysates were centrifuged at 12,000 rpm for 15 min. The supernatants were then passed over a 0.22 μm filter pre-layered with diatomaceous earth and the resulting filtrates loaded over VIVAPURE maxiprepMC Nickel affinity columns (Sartorius Stedim Biotech, Aubagne, France) using centrifugation (100 rpm for 5 min.). The columns were then washed 4 times using 10 ml PBS+30 mM imidazole (500 rpm for 3 min.) and the scFvs eluted using 20 ml PBS+300 mM imidazole (500 rpm for 3 min.). The eluted scFvs were concentrated using 10,000 molecular weight cut-off membrane VIVASPIN centrifuge tubes at 3000 rpm for 30 min. (Sartorius Stedim Biotech) and dialyzed back into regular PBS. The final scFv products were subsequently stored at −80° C.
Example 4
Construction of scFv-Fc Fusion Protein and Expression in DG44 CHO Cells
Using a proprietary antibody expression vector (referred to herein as IgG Vector), similar to that of pFUSE-hIgG1-Fc1 (InvivoGen; San Diego, Calif.), the construct was first modified to contain the CH 2 , and CH 3 domains of a human IgG 1 (scFv-Fc Vector). Subsequently, the EBNA Clone 315 and WT1 Clone 45 scFv sequences were PCR amplified to contain the required NheI and ApaI restriction sites which would be compatible with the scFv-Fc vector. The resulting scFv PCR products and antibody expression plasmid were digested using the above enzymes (NheI at 37° C. for 2 hours and ApaI at 25° C. for 2 hours) and then ligated together. The ligation products were then transformed into E. coli , plated on TYE+Amplicilin (100 μg/ml), colonies were picked and their plasmids sequenced at the MSKCC Sequencing Core Facility. Once the sequences were validated to have the correct scFv sequences upstream of the human IgG 1 CH 2 and CH 3 domains, the DNA (5-6 μg was electroporated (Amaxa NUCLEOFACTOR; Lonza, Switzerland) into 5×10 6 DG44 Chinese Hamster Ovary (CHO) Cells (Invitrogen) using Program U-030 and 100 μl Solution V. The cells were then cultured in OPTICHO media (Invitrogen) containing G418 (500 μg/ml; added 7 days post-electroporation) at a cell density of 1-5×10 6 DG44 per ml of media. The cells were then expanded to approximately 700 ml of culture media, which was centrifuged to remove the cells and supernatant used for antibody purification.
Example 5
Expression and Purification of Soluble scFv-Fc Fusion Protein
DG44 supernatant containing the soluble scFv-Fc fusion protein was purified using the KAPPASELECT affinity chromatograph medium (GE Healthcare). First, 1.5 ml of KAPPASELECT resin was loaded onto a column and activated with 20 ml of PBS. The supernatant was loaded onto the column using a peristaltic pump at a flow rate of approximately 1 ml/min. The column was subsequently washed using 40 ml of PBS until the flow-thru registered an OD280 of less than 0.05. The scFv-Fc fusion protein was then eluted from the resin using 10 ml citrate buffer (pH 2.0) and directly into 10 ml of 1 M Tris for neutralization. The eluted scFv-Fc was subsequently concentrated using a 50,000 MWCO VIVASPIN centrifuge tube (Sartorius Stedim) and tested for its ability to bind to recombinant antigen using ELISA and the BIACORE T100 (GE Healthcare) as well as natively presented peptide on the surface of T2 cells using flow cytometry.
Example 6
Monoclonal ELISA with Bacterial Phage Clones and Purified scFv and scFv-Fc
Vinyl flat bottom microtiter plates (Thermo Fisher) were used for ELISA assays. Plates were initially coated overnight at 4° C. with BSA-biotin (10 μg/ml; 50 μl/well). The next morning, the contents were discarded and the plates incubated at RT with streptavidin (10 μg/ml; 50 μl/well) for 1 hour. The contents were discarded and the plates incubated with recombinant biotinylated HLA-A2-peptide complexes (5 μg/ml; 50 μl/well) at RT for 1 hour. The plates were then incubated with 2% Milk (150 μl/well) at RT for 1 hour. After blocking, the plates were washed 2 times with PBS and then incubated with bacterial supernatant from their respective HB2151 culture plate wells, purified scFv, or purified scFv-Fc at RT for 1 hour. The contents were discarded, the plates washed 5 times with PBS, and then incubated at RT for 1 hour with either a mouse-anti-myc tag antibody (Clone 9E10; Sigma Aldrich. 0.5 μg/ml; 100 μl/well in 0.5% Milk) to detect the scFv or a goat-anti-human-HRP (Jackson Immunoresearch Laboratories. 0.5 μg/ml; 100 μl/well in 0.5% Milk) to detect the scFv-Fc. The contents were discarded, the plates washed 5 times with PBS, and those receiving the scFv were further incubated with a goat-anti-mouse-HRP (Jackson Immunoresearch Laboratories. 0.5 μg/ml; 100 μl/well in 0.5% Milk) at RT for 1 hour while the plates receiving the scFv-Fc were developed using o-phenylenediamine (OPD) buffer (150 μl/well), which was made by combining 20 mg of OPD tablets in 40 ml of citrate phosphate buffer with 40 μl 30% hydrogen peroxide. The color reaction was stopped by adding 30 μl of 5N sulfuric acid to each well and the plates read using the Dynex MRX ELISA plate reader at 490 nm. Lastly, the contents of the scFv plates were discarded, the plates washed 5 times with PBS, and developed according to the method above.
Example 7
Cell Lines and Peptides
Tap-deficient HLA-A2 + T2 cells, 6268A, GKO (both HLA-A2 − ), DIMT and JG19 (both HLA-A2 + ) B-cell lymphoblastic cell lines (BLCLs) were used for antigen presentation studies. Cells were normally cultured in RPMI 1640+10% Fetal Bovine Serum (FBS). For antigen presentation, T2 cells were harvested and transferred to serum-free IMDM+10 μg/ml β2-microglobulin (β2M). The T2 cells would then be incubated with 20 μM or less of either LLDFVRFMGV SEQ ID NO: 4) -peptide (derived from EBNA3C) or any number of irrelavent peptides at 37° C. for 5 hours. Studies with BLCLs were done in the same manner as with T2 cells with the occlusion of β 2 M in the media. Pulse-Chase experiments with DIMT BLCLs were done by first pulsing the BLCLs in serum-free IMDM with 20 μM LLDFVRFMGV SEQ ID NO: 4) for 5 hours at 37° C. The cells were then washed with fresh RPMI 1640+10% FBS, transferred back into this culture medium and cultured further at 37° C. for 5 and 24 hours, followed by flow cytometric analysis at each time point using EBNA Clone 315 scFv.
Example 8
Binding Kinetics Analysis
Kinetic measurements were performed by surface plasmon resonance using the BIACORE T100 (GE Biosciences). Briefly, the first two flow cells of a CM5 chip (GE Biosciences) were activated using the standard amine coupling reagents in HBS-EP running buffer (0.01 M HEPES, 0.15 M NaCl, 3 mM EDTA, 0.005% TWEEN 20) with flow cell 2 immobilized with the purified EBNA Clone 315 scFv-Fc fusion protein using 10 mM Acetate (pH 5). Subsequently, the target HLA-A2-peptide monomer (222 nM-13.875 nM) was injected over both the 1st (reference) and 2nd flow cells at 20 μl/min. for 120 sec., followed by the addition of running buffer for an extra 180 sec. Kinetics values were determined using the BIACORE T100 Evaluation Software 2.0 and 1:1 binding model (local Rmax).
Example 9
Flow Cytometry
Peptide-pulsed T2 cells and BLCLs were transferred to plastic polystyrene round-bottom tubes (Becton Dickinson Labware) and washed with PBS. The cells were subsequently incubated with 5 μg of either targeted or non-specific purified scFv or scFv-Fc on ice for 40 min. The cells were washed with PBS and then incubated with 1 μg of biotinylated mouse-anti-myc antibody (Clone 9E10; Sigma Aldrich) or biotinylated mouse-anti-human IgG Fc-specific (Jackson Immunoresearch Laboratories) on ice for 30 min. The cells were washed with PBS and then incubated with streptavidin-PE (BD Biosciences). Lastly, the cells were washed once more with PBS and analyzed on the BD FACS Calibur.
For CD107a cytotoxicity assays, transduced-NK92MI cells and target T2 cells were cocultured in a 1:1 effector:target (E:T) ratio (2.5-5.0×10 5 cells each) in 200 μl complete Alpha Essential medium (12.5% horse serum and 12.5% FBS) (Invitrogen)+10-15 μl anti-CD107a-PE at 37° C. for 5 Hours. The cell mixture was then washed with PBS and analyzed on the BD FACS Caliber.
For FACS sorting experiments, retrovirally transduced NK92MI cells were sorted based on GFP intensity using the BD Aria Flow Cytometer under the guidence of the MSKCC Flow Cytometry facility.
Example 10
Quantitation of HLA-A2-LLDFVRFMGV SEQ ID NO: 4) Complexes on Peptide-Pulsed T2 Cells
For MHC-peptide complex quantitation, the EBNA Clone 315 scFv-Fc was first directly conjugated to ALEXA FLUOR 647 using the APEX ALEXA FLUOR 647 Antibody Labeling Kit (Invitrogen). The kit yields about 10-20 μg of labeled antibody.
For quantitation, the QUANTUM SIMPLY CELLULAR anti-Human IgG kit was used (Bangs Laboratories) along with the technical assistance of Hong-fen Guo in our laboratory. Briefly, the kit is comprised of five microsphere populations; one blank and four labeled with increasing amounts of anti-human IgG. The beads and the peptide pulsed T2 cells (37° C. for 5 hours) were then labeled with the same fluorescently conjugated EBNA Clone 315 scFv-Fc on ice for 30 minutes. The cells were then washed with PBS and analyzed on the BD FACS Calibur along with the labeled beads. The Excel-based QuickCal analysis template that's provided with each kit aids in correlating fluorescence intensity with antigen density on the T2 cells. Each of the 4 data points are the average of duplicates.
Example 11
Construction of the WT-1 Clone 45 Chimeric Antigen Receptor
The original chimeric antigen receptor was obtained from Dr. Dario Campana from St. Jude Children's Hospital and previously described (41). For future compatibility purposes, a scFv-CD3ζ-4-1 BB DNA construct (similar to that seen in the original chimeric immune receptor, with EcoRI and XhoI flanking the 5′ and 3′ ends) was purchased (pUC57 vector from Genescript; Piscataway, N.J.) and contained an irrelevant scFv flanked by SfiI and NotI. The plasmid containing the EBNA Clone 315 scFv sequence (pIT2 vector from the Tomlinson library) was purified (Qiagen miniprep DNA isolation kit) from overnight culture of the bacterial stock in LB+Amplicilin (100 μg/ml). The scFv sequence was excised from the pIT2 vector using SfiI (50° C. for 2 hours) and NotI (37° C. for 2 hours) inserted into the purchased and predigested (SfiI and NotI) pUC57 vector. After ligation, the product was transformed into NEB 5-alpha competent E. coli (New England Biolabs), the cells plated on TYE+Amplicilin (100 μg/ml), colonies were picked and cultured in LB+Amplicilin (100 μg/ml), their plasmids purified and the product sizes were verified by gel electrophoresis. Plasmids which were found to have the correct ligation products were subsequently excised from the pUC57 vector using EcoRI (37° C. for 2 hours) and XhoI (37° C. for 2 hours) and used for insertion into the vector provided to us by the Campana laboratory. The ligation products were then transformed into E. coli as above, plated on TYE+Amplicilin (100 μg/ml), colonies were picked and their plasmids sequenced using the reverse primer 788A (5′-CCCTTGAACCTCCTCGTTCGACC-3′) (SEQ ID NO: 72) at the MSKCC Sequencing Core Facility. Once the sequences were validated, the DNA was packaged into retrovirus and used to infect NK92MI cells.
Example 12
Construction of the EBNA Clone 315 Chimeric Antigen Receptor
Due to compatibility issues, the pUC57 scFv-CD3ζ-4-1 BB DNA construct purchased from Genescript and mentioned above was used to replace the WT1 Clone 45 scFv with the EBNA Clone 315 scFv. First, the plasmid containing the EBNA Clone 315 scFv sequence (pIT2 vector from the Tomlinson library) was purified (Qiagen miniprep DNA isolation kit) from overnight culture of the bacterial stock in LB+Amplicilin (100 μg/ml). The scFv sequence was excised from the pIT2 vector using SfiI (50° C. for 2 hours) and NotI (37° C. for 2 hours) and ligated to the predigested (SfiI and NotI) pUC57 vector. After ligation, the product was transformed into E. coli , colonies were picked, cultured overnight, their plasmids purified and the product sizes verified by gel electrophoresis. Plasmids which were found to have the correct ligation products were subsequently excised from the pUC57 vector using EcoRI (37° C. for 2 hours) and XhoI (37° C. for 1 minute). Due to the presence of a XhoI site inside of the EBNA Clone 315 scFv sequence, the DNA was partially digested with XhoI and then completely digested using EcoRI. This allowed for the isolation of the correct DNA fragment which kept the integrity of the scFv sequence while removing the entire CAR sequence from the pUC57 vector. After insertion into the vector provided to us by the Campana laboratory, the ligation products were then transformed into E. coli as above, plated on TYE+Amplicilin (100 μg/ml), colonies were picked and their plasmids sequenced using the reverse primer 788A (5′-CCCTTGAACCTCCTCGTTCGACC-3′) (SEQ ID NO: 72) at the MSKCC Sequencing Core Facility. Once the sequences were validated, the DNA was packaged into retrovirus and used to infect NK92MI cells.
Example 13
Retroviral Production, DNA Packaging, and Infection of NK92MI Cells
To produce CAR-containing retrovirus, the following procedure was employed which used a 293T-based retroviral production cell line (GP2). Briefly, 7 μg of CAR DNA was combined with 3.5 μg of PCLAmpho helper construct and 3.5 μg pVSVg in 1 ml of serum-free DMEM. This mixture was then combined with 1 ml serum-free DMEM containing 36 μl of LIPOFECTAMINE 2000 (Invitrogen) and incubated at RT for 20 min. Afterwards, the DNA-LIPOFECTAMINE complex (2 ml) was mixed with GP2 cells (3-5×10 6 ) in 10 ml of DMEM+10% FBS and cultured at 37° C. for 72 hours. Subsequently, the supernatant (12 ml) was depleted of GP2 cells during recovery and incubated with 3 ml LENTI-X Concentrator solution (Clontech) at 4° C. for 12-16 hours. Afterwards, the solution was centrifuged at 3000 rpm for 15 min., the supernatant discarded, and the pellet dissolved in 1 ml complete Alpha Essential medium containing 5×10 5 NK92MI cells. The cells were then incubated for 72 hours and checked by flow cytometry for CAR expression via GFP (the CAR gene is expressed under a CMV promoter which is followed by IRES-GFP).
Example 14
Construction of scFv-Fc Fusion Protein and Expression in DG44 CHO Cells
Using a proprietary antibody expression vector similar to that of pFUSE-hIgG1-Fc1 (Invivogen; San Diego, Calif.), the Clone 315 scFv sequence was first PCR amplified to contain the required NheI and ApaI restriction sites. The resulting PCR product and expression plasmid were digested using the above enzymes (NheI at 37° C. for 2 hours and ApaI at 25° C. for 2 hours) and ligated together. The ligation products were then transformed into E. coli , plated on TYE+Amplicilin (100 μg/ml), colonies were picked and their plasmids sequenced at the MSKCC Sequencing Core Facility. Once the sequences were validated to have the Clone 315 scFv sequence upstream of the human IgG 1 CH2 and CH3 domains, the DNA was electroporated (Amaxa NUCLEAOFACTOR; Lonza, Switzerland) into 5×10 6 DG44 Chinese Hamster Ovary (CHO) Cells (Invitrogen) using Program U-030 and 100 μl Solution V. The cells were then cultured in OPTICHO media (Invitrogen) containing G418 (500 μg/ml; added 7 days post-electroporation) at a cell density of 1-5×10 6 DG44 per ml of media.
Example 15
Retroviral Production, DNA Packaging, and Infection of NK92MI Cells
To produce CAR-containing retrovirus, the following procedure was employed which used a 293T-based retroviral production cell line (GP2). Briefly, 7 μg of CAR DNA was combined with 3.5 μg of PCLAmpho helper construct and 3.5 μg pVSVg in 1 ml of serum-free DMEM. This mixture was then combined with 1 ml serum-free DMEM containing 36 μl of LIPOFECTAMINE 2000 (Invitrogen) and incubated at RT for 20 min. Afterwards, the DNA-LIPOFECTAMINE complex (2 ml) was mixed with GP2 cells (3-5×10 6 ) in 10 ml of DMEM+10% FBS and cultured at 37° C. for 72 hours. Subsequently, the supernatant (12 ml) was depleted of GP2 cells during recovery and incubated with 3 ml LENTI-X Concentrator solution (Clontech) at 4° C. for 12-16 hours. Afterwards, the solution was centrifuged at 3000 rpm for 15 min., the supernatant discarded, and the pellet dissolved in 1 ml complete Alpha Essential medium containing 5×10 5 NK92MI cells. The cells were then incubated for 72 hours and checked by flow cytometry for CAR expression via GFP (the CAR gene is expressed under a CMV promoter which is followed by IRES-GFP).
Example 16
51 Cr Release Cytotoxicity Assay
The capacity of CAR equipped NK92MI cells to lyse BLCLs was evaluated using a 51 Chromium release assay. Briefly, peptide pulsed or unpulsed 51 Cr-labeled BLCLs were plated in round-bottom 96-well plates (5×10 3 cells/well) in RPMI 1640 with 10% FBS. Subsequently, CAR equipped NK92MI cells were added to the BLCL containing wells at different effector (E)/target (T) ratios and incubated for 4 hours at 37° C., after which the cultures were depleted of cells and 51 Cr-release was measured in the supernatants. All E:T ratios were done in triplicate, with the average plotted on the graphs. % 51 Cr Release was determined using the following formula: ((Sample Release−Spontaneous Release)/(Total Release−Spontaneous Release))×100.
Example 17
Affinity Selection of Phage on Virally-Derived Recombinant HLA-A2-Peptide Complexes
Biotinylated and non-biotinylated recombinant HLA-A2-peptide complexes presenting various different peptides previously shown to bind to HLA-A2 were obtained from the MSKCC Tetramer Core Facility. For selection purposes, the Tomlinson I and J phage display libraries were combined and first preincubated with non-biotinylated, irrelevant HLA-A2-YVDPVITSI (SEQ ID NO: 75) complex along with streptavidin paramagnetic beads so that any phage which expresses an antibody that may bind to the general framework of HLA-A2, or the streptavidin beads themselves, are eventually discarded during the washing steps. Subsequently, the contents (phage and irrelevant complex) were incubated with biotinylated HLA-A2-LLDFVRFMGV (SEQ ID NO: 4) (EBNA3C) and biotinylated HLA-A2-NLVPMVATV (SEQ ID NO: 73) (pp65) simultaneously in equimolar ratios and captured using streptavidin paramagnetic beads. Once the beads were bound to the biotinylated complexes, the beads were washed with PBS containing TWEEN 20 and the bound phage were eluted from the beads using trypsin. After two additional rounds of selection, the recovered phage were used to infect HB2151 E. coli and plated on ampicillin-containing agar. The next morning, individual colonies were picked, cultured overnight in 48-well culture plates, and their supernatants tested for the presence of scFv on 96-well ELISA plates pre-coated with recombinant HLA-A2-peptide complexes.
The first three rounds of selection resulted in a 55-fold increase in phage recovery, based on output/input ratio, and scFvs which only bound to the HLA-A2-EBNA3C complex. Phage display selection results on recombinant HLA-A2-LLDFVRFMGV (SEQ ID NO: 4) and HLA-A2-NLVPMVATV (SEQ ID NO: 73) complexes are shown in Table 9.
TABLE 9
Round 1*
Round 2*
Round 3*
Round 4**
Input
7.5 × 10 12
4.9 × 10 12
2.4 × 10 12
1.8 × 10 12
Output
4.7 × 10 6
6 × 10 6
8.4 × 10 7
1.25 × 10 8
Output/Input
6.3 × 10 −7
1.22 × 10 −6
3.5 × 10 −6
6.9 × 10 −5
Fold Enrichment
—
2
55.5
109.5
(From Rd 1)
HLA-A2-
—
—
40/48 (83%)
37/48 (77%)
EBNA3C
Peptide-Specific
Clones***
HLA-A2-pp65
—
—
0/48 (0%)
0/48 (0%)
Peptide-Specific
Clones***
*Rd 1-3: Panning against Biotinylated-HLA-A2-pp65 Peptide + Biotinylated-HLA-A2-EBNA Peptide
**Rd 4: Panning against Biotinylated HLA-A2-EBNA3C Peptide Only
***Relative signal at least 2-fold greater than background.
These results were somewhat surprising since both of the peptides on HLA-A2 were derived from viral-related proteins, which are not seen in the human protein repertoire. To confirm these findings, an additional round of selection was undertaken on just the HLA-A2-EBNA3C complex alone which resulted in a further amplification of recovered phage (109-fold) and a similar percentage of clones which bound to the HLA-A2-EBNA3C complex (83% positive after Round 3 and 77% after Round 4).
Bacterial supernatant from individual clones after 3 rounds of phage selection were tested for binding to recombinant, biotinylated-HLA-A2-peptide complexes on vinyl microtiter plates. While several clones resulted in cross-reactivity to more than just the targeted HLA-A2-LLDFVRFMGV (SEQ ID NO: 4) complex (Clones 335 and 345), Clones 315 and 327 were found to have the desired specificity.
Purified EBNA Clone 315 scFv was retested against a similar panel of recombinant, biotinylated HLA-A2-peptide complexes. Purified EBNA Clone 315 scFv maintained its specificity over a panel of HLA-A2-peptide complex in addition to its inability to bind to the native peptide by itself. The anti-HLA-A2 antibody BB7.2 was included to demonstrate that all HLA-A2-peptide complexes are adherent and presented properly on the plate.
During the screening processes, therefore, several different scFv were found to bind to the targeted HLA-A2-EBNA3C complex, however only a few scFv sequences resulted in absolute specificity and did not bind to HLA-A2-peptide complexes of different origins ( FIG. 1A ). Of those clones which were tested, EBNA Clones 315 and 327 had the same peptide sequence and were further characterized. After scFv purification, a subsequent validation ELISA demonstrates that EBNA Clone 315 maintained its specificity towards the targeted HLA-A2-EBNA complex, in addition to failing to bind to the LLDFVRFMGV (SEQ ID NO: 4) peptide by itself ( FIG. 1B ). These initial binding assays demonstrate the TCR-like binding ability of this antibody.
Example 18
Affinity Selection of Phage on WT1-Derived Recombinant HLA-A2-Peptide Complex
Antibody selection using phage against biotinylated HLA-A2-RMFPNAPYL (SEQ ID NO: 1) (WT1-derived) was done in a similar manner to that which was described above. Briefly, the Tomlinson I and J phage display libraries were first combined and preincubated with non-biotinylated, irrelevant HLA-A2-NLVPMVATV (SEQ ID NO: 73) complex and streptavidin paramagnetic beads. Subsequently, the contents (phage and irrelevant complex) were incubated with biotinylated HLA-A2-RMFPNAPYL (SEQ ID NO: 1) and captured using fresh streptavidin paramagnetic beads. Once bound to the biotinylated complex, the beads were washed with PBS containing TWEEN 20 and the bound phage were eluted from the beads using trypsin. After two additional rounds of selection, the recovered phage were used to infect HB2151 E. coli and plated on ampicillin-containing agar. The next morning, individual colonies were picked, cultured overnight in 48-well culture plates, and their supernatants tested for the presence of scFv on 96-well ELISA plates pre-coated with recombinant HLA-A2-peptide complexes.
The first three rounds of selection resulted in a 90-fold enrichment in phage when comparing the output/input ratios. Phage display selection results on recombinant HLA-A2-RMFPNAPYL (SEQ ID NO: 1) complex are shown in Table 10.
TABLE 10
Round 1*
Round 2**
Round 3**
Input
3.7 × 10 12
5.6 × 10 11
1.55 × 10 11
Output
4.0 × 10 6
3.2 × 10 6
1.52 × 10 7
Output/Input
1.08 × 10 −6
5.7 × 10 −6
9.8 × 10 −5
Fold Enrichment
—
5.3
90.7
(From Rd 1)
HLA-A2-
—
—
3/48
RMFPNAPYL-
Specific Clones***
*Rd 1: Panning against 5 μg Complex.
**Rd 2-3: Panning against 2.5 μg Complex.
***Relative signal at least 3-fold greater than background (Irrelevant HLA-A2-Complex).
Bacterial supernatant from three individual clones after three rounds of phage selection were tested for binding to recombinant, biotinylated-HLA-A2-peptide complexes on vinyl microtiter plates. All three clones which were tested had the necessary specificity to only recognize the HLA-A2-RMFPNAPYL (SEQ ID NO: 1) complex. It was discovered that all three clones had the same DNA sequence. Purified WT1 Clone 45 scFv was retested against a similar panel of recombinant, biotinylated HLA-A2-peptide complexes. Purified WT1 Clone 45 scFv maintained its specificity over a panel of HLA-A2-peptide complex in addition to its inability to bind to the native peptide outside of the context of MHC. The anti-HLA-A2 antibody BB7.2 was included to demonstrate that all HLA-A2-peptide complexes are adherent and presented properly on the plate.
After screening 48 clones for binding to the specific HLA-A2-RMFPNAPYL complex, therefore, three clones were found to bind specifically to their targeted complex but failed to bind to complexes which displayed an irrelevant peptide ( FIG. 2A ). Of the clones which were tested, all of them were found to have the same peptide sequence and WT1 Clone 45 was chosen for further characterization. After scFv purification, a subsequent validation ELISA demonstrates that WT1 Clone 45 maintained its specificity towards the targeted HLA-A2-WT1 complex, in addition to failing to bind to the RMFPNAPYL (SEQ ID NO: 1) peptide by itself ( FIG. 2B ). These initial binding assays demonstrate the TCR-like binding ability of this antibody.
Example 19
Binding and Specificity Studies with Purified EBNA Clone 315 and WT1 Clone 45 scFvs on Peptide-Pulsed T2 Cells
To demonstrate that the isolated EBNA Clone 315 and WT1 Clone 45 scFvs are able to recognize and bind to their native complexes on the surface of peptide-pulsed antigen presenting cells (APCs), the TAP-deficient T2 cell line was used. T2 cells were first incubated for 5 hours at 37° C. with either LLDFVRFMGV (SEQ ID NO: 4) (EBNA3C-derived), RMFPNAPYL (SEQ ID NO: 1) (WT1-derived) or irrelevant peptide KLQCVDLHV (SEQ ID NO: 74) in serum-free medium containing β 2 M. The cells were subsequently washed and stained with the purified WT1 Clone 45, EBNA Clone 315 or an irrelevant scFv. In addition, peptide pulsed and unpulsed T2 cells were also incubated with an anti-HLA-A2-FITC (BB7.2) antibody. This BB7.2 staining control was included due to previous studies which demonstrate that if a peptide is able to bind HLA-A2 on the T2 cell surface, the HLA-A2 molecule is stabilized, and the stabilization can be visualized by an increase in fluorescence intensity (81). As shown in FIG. 3A , T2 cells which have been pulsed with either the LLDFVRFMGV (SEQ ID NO: 4) or KLQCVDLHV (SEQ ID NO: 74) peptides resulted in a fluorescence shift, consistent with their binding to the HLA-A2 pocket. However, EBNA Clone 315 was only able to stain T2 cells pulsed with its specific target peptide LLDFVRFMGV (SEQ ID NO: 4) and not an irrelevant peptide ( FIG. 3B ). Similar results were obtained when T2 cells were pulsed with either the RMFPNAPYL (SEQ ID NO: 1) or LLDFVRFMGV (SEQ ID NO: 4) peptides and stained with WT1 Clone 45 scFv. While both peptides were able to stabilize the HLA-A2 molecule ( FIG. 4A ), WT1 Clone 45 scFv was only able to detect the T2 cells pulsed with the RMFPNAPYL (SEQ ID NO: 1) peptide ( FIG. 4B ). This further validates their utility in detecting the native complex on the surface of cells.
Next, the detection sensitivity of the EBNA Clone 315 scFv using flow cytometry was evaluated in order to correlate sensitivity with antigen density using flow cytometric quantitative beads. Briefly, TAP-deficient T2 cells were pulsed with (solid, unfilled lines) or without (dashed, unfilled lines) LLDFVRFMGV (SEQ ID NO: 4) ( FIG. 3A , top, left panel) or KLQCVDLHV (SEQ ID NO: 74) peptides ( FIG. 3A top, right panel) at 20 μM in serum-free IMDM media at 37° C. for 5 hours. The cells were then stained with a mouse-anti-human HLA-A2-FITC conjugated antibody (unfilled lines) or a control mouse IgG 1 -FITC conjugated antibody (filled lines) and analyzed on the FACS machine. Peptide-pulsed T2 cells from A were stained with EBNA Clone 315 scFv (unfilled lines) or a control scFv (filled lines) ( FIG. 3B ). Only T2 cells which had been pulsed with the LLDFVRFMGV (SEQ ID NO: 4) peptide (left panel), but not ones which had been pulsed with KLQCVDLHV (SEQ ID NO: 74) (right panel), could be stained by the EBNA Clone 315 scFv ( FIG. 3B ). T2 cells were incubated with decreasing concentrations of the LLDFVRFMGV (SEQ ID NO: 4) peptide and subsequently stained with EBNA Clone 315 scFv as above ( FIG. 3C ). Based on geometric mean fluorescence (control scFv background subtracted), the lower limit of detection corresponds with 78 nM of peptide used for pulsing.
By titrating down the amount of peptide used for incubation with the T2 cells, it was determined that concentrations as low as 78 nM were still able to produce a fluorescence signal above background when stained with EBNA Clone 315 scFv ( FIG. 3C ). With decreasing concentrations of peptide used for loading, there was a corresponding reduction in overall HLA-A2 intensity (data not shown) as one would expect.
Similarly, FIG. 4 shows that WT1 Clone 45 can recognize HLA-A2-RMFPNAPYL (SEQ ID NO: 1) on peptide-pulsed T2 cells. TAP-deficient T2 cells were pulsed with (solid, unfilled lines) or without (dashed, unfilled lines) RMFPNAPYL (SEQ ID NO: 1) (left panel) or LLDFVRFMGV (SEQ ID NO: 4) peptides (right panel) at 40 μM in serum-free IMDM media at 37° C. for 5 hours. The cells were then stained with a mouse-anti-human HLA-A2-FITC conjugated antibody (unfilled lines) or a control mouse IgG1-FITC conjugated antibody (filled lines) and analyzed on the FACS machine ( FIG. 4A ). Peptide-pulsed T2 cells from A were stained with WT1 Clone 45 (unfilled lines) or a control scFv (filled lines). Only T2 cells which had been pulsed with the RMFPNAPYL (SEQ ID NO: 1) peptide (left panel), but not ones which had been pulsed with LLDFVRFMGV (SEQ ID NO: 4) (right panel), could be stained by the WT1 Clone 45 ( FIG. 4B ).
Example 20
Demonstrating HLA Restriction of the LLDFVRFMGV (SEQ ID NO: 4) Peptide and EBNA Clone 315 Using Peptide-Pulsed BLCLs
The expression of these peptides on BLCLs, especially since BLCLs are used routinely as APCs (82), was examined. Two BLCL lines were used, one HLA-A2 + (DIMT) and one HLA-A2 − (6268A) ( FIG. 5A ). The BLCLs were incubated in serum-free IMDM media for 5 hours at 37° C. with either the specific LLDFVRFMGV (SEQ ID NO: 4) or irrelevant KLQCVDLHV (SEQ ID NO: 74) peptides. When incubated with the specific peptide, only the HLA-A2 + DIMT BLCL could be stained by EBNA Clone 315 ( FIG. 5B ). Similarly to results seen with T2 cells, DIMT cells loaded with the irrelevant peptide, or 6268A loaded with the specific/irrelevant peptide, could not be stained with EBNA Clone 315. It is interesting to note that without peptide pulsing we were unsuccessful at staining DIMT. While our staining approach has been optimized to detect low levels of antigen through signal amplification involving secondary and tertiary reagents to detect the scFv, the amount of peptide that the cell naturally presents seems to be below our level of detection.
Subsequently, in an attempt to study the duration of peptide presentation on HLA-A2, a pulse-chase experiment was set up to monitor the levels of the HLA-A2-EBNA3C complex on DIMT cells over time. Initially, DIMT cells were incubated in serum-free IMDM media for 5 hours at 37° C. with the LLDFVRFMGV (SEQ ID NO: 4) peptide. Afterwards, the cells were washed twice with RPMI+10% FBS and further cultured in this media for an additional 5 hours and 24 hours. At each of these three time points, cells were harvested and stained with either the purified EBNA Clone 315 scFv or an irrelevant scFv. The results show that after pulsing the HLA-A2-EBNA3C complex could easily be detected on the cell surface ( FIG. 5C ). Interestingly, even after the cells were transferred to fresh media and cultured for an additional 5 and 24 hours, the MHC-peptide complex could still be detected, signifying that peptide-pulsed BLCLs are able to hold onto and present antigen for at least a day after the peptide had been removed from the media. This data further supports the use of autologous BLCLs in the generation of antigen specific T cells and the utility of TCE-specific antibodies like EBNA Clone 315 in precise visualization of TCE expression on APCs or target cells.
Example 21
Construction of EBNA Clone 315 and WT1 Clone 45 scFv-Fc Fusion Proteins
Initially, the scFv sequences were made compatible for cloning into a scFv-Fc expression vector by using PCR to add the desired restriction enzyme sites (NheI and ApaI) to either side of the EBNA Clone 315 and WT1 Clone 45 scFv sequences. The PCR reaction was done on the Tomlinson library vector which contained the WT1 Clone 45 and EBNA Clone 315 scFv sequences ( FIG. 7A ). After subsequent digestion using NheI and ApaI, the digested PCR products were removed from a 1% agarose gel and purified ( FIG. 6B ).
With regards to cloning and expression of the scFv-Fc fusion proteins, a proprietary vector obtained from Eureka therapeutics (IgG Vector) was used. The first constant heavy chain (CH 1 ) was removed from this vector, something which is typically done when generating Fc fusion proteins (83). Once generated, the vector was digested with NheI and ApaI and then ligated to the predigested PCR products from FIG. 7B . The ligated products yielded a vector which expressed the EBNA Clone 315 or WT1 Clone 45 scFv genes in tandem to the CH 2, 3 domains of a human IgG1 under a single CMV promoter (scFv-Fc Vector; FIG. 7B ). After further validation using DNA sequencing, the two fusion constructs were linearized using HindIII and ran on a 1% agarose gel. Digestion with HindIII also allowed us to block the expression of the light chain that is still present in the vector, which for all intensive purposes was undesired. As expected, both digested plasmids ran at the anticipated size (˜11,000 bp) based on their location relative to the lambda HindIII marker. Each linearized plasmid was subsequently introduced into DG44 cells and cultured in OPTICHO media as described in Example 10 above.
Example 22
Binding Kinetics and Sensitivity of EBNA Clone 315 scFv-Fc on Recombinant HLA-A2-Peptide Complex and Peptide-Pulsed T2 Cells
To further understand the affinity of the interaction between EBNA Clone 315 and the HLA-A2-EBNA3C complex, surface plasmon resonance was used to determine the binding kinetics between these two proteins. First, the EBNA Clone 315 scFv-Fc was purified and its binding ability was tested using ELISA ( FIG. 8A ) along with flow cytometry via peptide-pulsed T2 cells at varying concentrations ( FIGS. 8B and C). These initial studies demonstrate that the antibody maintains its binding characteristics when expressed as a fusion protein In addition, it is important to note that the flow cytometric sensitivity of the scFv and scFv-Fc were very comparable (200 nM-20 nM), further highlighting the utility of the scFv as a monomeric binding fragment.
Next, using the BIACORE T100 (GE Healthcare), a CM5 chip (flow cells 1 and 2) was initially activated for amine coupling based on manufacturer recommendation. The purified EBNA Clone 315 scFv-Fc was subsequently immobilized onto the second flow cell and the purified HLA-A2-EBNA3C complex passed over both flow cells as part of the soluble phase. After background subtraction (signal from flow cell 2 minus that of flow cell 1), the association rate (k on ) and dissociation rate (k off ) were determined (2.361×10 5 M −1 s −1 and 6.891×10 −2 s −1 , respectively), resulting in an overall K D (k off /k on ) of 291 nM using a 1:1 binding model ( FIG. 9 ); these kinetic rates were very similar to previously isolated Fabs against different MHC-peptide complexes (22, 31). Relative to published TCR:MHC Class I-peptide K D measurements, which typically range in the neighborhood of 2-50 μM (84), our scFv:MHC Class I-peptide interaction seems to be at best 150-fold stronger, with the most significant improvement attributed to a slower k off . Previous studies which support an affinity-based T cell activation model argue that a greater overall affinity or slower dissociation rate leads to higher interferon-gamma release and target cell lysis (85, 86).
Lastly, in an attempt to quantify the amount of HLA-A2-LLDFVRFMGV (SEQ ID NO: 4) complex on the surface of peptide-pulsed T2 cells, we decided to use flow cytometric quantitation beads. This data will also be useful in determining the detection threshold of EBNA Clone 315 scFv and scFv-Fc. First, purified EBNA Clone 315 scFv-Fc was conjugated to a fluorescent label, ALEXA FLUOR 647 using a commercially available kit. Subsequently, T2 cells were pulsed with 20, 10, 5, or 0 μM of LLDFVRFMGV (SEQ ID NO: 4) peptide at 37° C. for 5 hours. After pulsing, the peptide-pulsed T2 cells, along with beads containing known quantities of anti-human IgG 1 antibodies, were incubated with the fluorescently-labeled EBNA Clone 315 scFv-Fc. Once the cells and beads were analyzed on the FACS machine, the fluorescence intensities were correlated to each other, resulting in an estimation of the number of complexes on the surface of the T2 cells relative to the quantity of peptide used for pulsing. These four values (337,091 sites with 20 μM, 149,688 sites with 10 μM, 76,040 sites with 5 μM, and no sites with 0 μM) were plotted on a graph and a trendline was used to create a standard curve (R 2 =0.9948) ( FIG. 10A ). Furthermore, when looking at the lower end of the spectrum, we have determined that an amount less than 40 nM of peptide will correspond to less than 100 complexes on the surface of the cell ( FIG. 10B ), placing the detection level of the EBNA Clone 315 scFv-Fc fusion within that range.
Example 23
Binding and Specificity Studies of WT1 Clone 45 scFv-Fc on Recombinant HLA-A2-Peptide Complex and Peptide-Pulsed Cells
In order to do further studies regarding the presentation of the RMFPNAPYL (SEQ ID NO: 1) peptide on the surface of APCs, the WT1 Clone 45 scFv-Fc fusion protein was first purified and validated for binding to its targeted recombinant HLA-A2-peptide complex ( FIG. 11A ). As was shown with the scFv, the fusion protein maintained its binding ability on the ELISA plate. Next, we decided to check and see if the scFv-Fc maintained its binding ability and specificity on peptide-pulsed T2 cells. T2 cells were pulsed with the RMFPNAPYL (SEQ ID NO: 1) peptide or an irrelevant peptide in serum-free media with β 2 M at 37° C. for 5 hours. Using flow cytometry, the scFv-Fc was able to detect T2 cells which had been pulsed with the RMFPNAPYL (SEQ ID NO: 1) peptide, but failed to recognize the cells pulsed with an irrelevant peptide ( FIG. 11B ). These two assays further validated that the fusion protein acts in the same way as the original scFv.
Subsequently, we decided to test whether the binding of the RMFPNAPYL (SEQ ID NO: 1) peptide and scFv-Fc fusion protein were restricted to HLA-A2. HLA-A2 + and HLA-A2 − BLCLs (DIMT and 6268A, respectively) were pulsed with the RMFPNAPYL (SEQ ID NO: 1) peptide in serum-free media at 37° C. for 5 hours. Similarly to EBNA Clone 315, the WT1 Clone 45 scFv-Fc fusion protein was only able to recognize the peptide pulsed DIMT and not the HLA-A2 − 6268A BLCL ( FIG. 12 ). These results demonstrate that the RMFPNAPYL (SEQ ID NO: 1) peptide is restricted to HLA-A2 and WT1 Clone 45 is only able to recognize it in the context of this complex.
Example 24
Antibody-Dependent Cellular Cytotoxicity (ADCC) of EBNA Clone 315 scFv-Fc on Peptide-Pulsed Cells
In addition to using the scFv-Fc for antigen presentation studies, we tested whether the truncated human IgG 1 Fc region is capable of inducing antibody-dependent cellular cytotoxicity (ADCC). In order to avoid variability amongst human donor lymphocytes, and in an effort to increase the chances of observing cytotoxicity, Hong-fen Guo in our laboratory generated a CD16(V)-transduced NK92MI cell line. This NK92 cell variant is transduced with both IL-2 and the human CD16 activating Fc receptor (FcγRIIIA) containing a high affinity polymorphism (valine instead of phenylalanine at position 158 on CD16) responsible for an enhancement in ADCC and clinical response to antibody-based immunotherapy (87, 88).
We used this cell line in combination with the EBNA Clone 315 scFv-Fc or an irrelevant, isotype-matched scFv-Fc to test whether the fusion protein can induce NK92MI-mediated ADCC against LLDFVRFMGV (SEQ ID NO: 4) -pulsed LUY (HLA-A2 + ) BLCL. At an E:T ratio of 42:1, EBNA Clone 315 scFv-Fc led to greater killing over background (with or without an irrelevant scFv-Fc) at the two highest concentrations tested (27-32% versus 13-15%) ( FIG. 13 ). A similar magnitude of killing (over background) was also observed with other peptide-pulsed, HLA-A2 + target BLCLs (DIMT and JG19). These results show that these truncated scFv-Fc fusion proteins maintain their Fc-mediated effector functions, despite being about 33% smaller than a full immunoglobulin.
Example 25
Construction and Retroviral Transduction of an HLA-A2-RMFPNAPYL (SEQ ID NO: 1)-Specific Chimeric Antigen Receptor into NK92MI Cells
In order to generate a CAR specific for the HLA-A2-RMFPNAPYL (SEQ ID NO: 1) complex, the WT1 Clone 45 scFv would typically be fused to intracellular signaling domains of immune-modulatory proteins found in immune effector cells. A CAR expression vector (St. Jude CAR) in which a CD19-specific scFv is fused to the CD8a hinge/transmembrane region, 4-1 BB and CD3 chain was obtained and modified so that the anti-CD19 scFv was replaced with a WT1 Clone 45 scFv. However, due to restriction enzyme incompatibility issues between the St. Jude CAR vector and the Tomlinson library vector used for PCR, the entire CAR gene, containing the WT1 Clone 45 scFv, was commercially synthesized by Genescript. The resulting WT1 pUC57 vector contained the desired WT1 Clone 45 CAR sequence flanked by EcoRI and XhoI.
An additional feature to the St. Jude CAR vector is an IRES-GFP sequence downstream of the CAR sequence. This allows for direct correlation of CAR expression with GFP without having to fuse both proteins together. In order to take advantage of this feature, we digested the WT1 pUC57 vector and St. Jude CAR vector using EcoRI and XhoI. Afterwards, the digested and undigested plasmids were run on a 1% agarose gel along with the lambda HindIII and 100 bp markers. The highlighted bands corresponded to the anticipated sizes of the St. Jude plasmid lacking the CAR sequence (˜6500 bp) and the WT1 Clone 45 CAR sequence lacking the pUC57 plasmid (˜1500 bp). These bands were excised from the gel, and after DNA purification, the two were ligated together. After the ligation products were transformed into E. coli, 8 colonies were selected at random and their plasmids isolated. The isolated plasmids were then validated by sequencing to determine whether they contain the WT1 Clone 45 scFv sequence in the context of the CAR. In addition, the plasmids were also digested with EcoRI and XhoI and run on a 1% agarose gel along with lambda HindIII and 100 bp markers to validate their sizes. After demonstrating that both bands from each plasmid yielded the expected sizes, it was determined that the cloning was successful.
Once the WT1 Clone 45 CAR was generated ( FIG. 23 ), the DNA was packaged into retrovirus using the 293T-based GP2 cell line. Once the retrovirus was generated in the culture media, it was recovered and concentrated. The concentrated virus was then used to infect 500,000 to 1,000,000 NK92MI cells in NK92MI growth media. After 3-4 days of culture, the NK92MI cells infected with the retrovirus were compared to mock-infected cells (infected with empty retrovirus) with regards to GFP expression using flow cytometry. While the infection efficiency was approximately 27.5%, flow assisted cytometric cell sorting (FACS) allowed us to enrich the GFP-positive population to more than 98% positive ( FIG. 23 ).
Example 26
Construction and Retroviral Transduction of an HLA-A2-LLDFVRFMGV (SEQ ID NO: 4) -Specific Chimeric Antigen Receptor into NK92MI Cells
Since the WT1 Clone 45 CAR required us to purchase the WT1 pUC57 vector, additional restriction sites were added to this construct for greater ease when swapping different scFvs. As a result, the EBNA Clone 315 scFv sequence could directly be cloned out of the Tomlinson vector from which it was derived.
The first cloning step involved the removal of the WT1 Clone 45 scFv from the WT1 pUC57 vector using SfiI and NotI. The same digestion was done to the Tomlinson vector containing the EBNA Clone 315 scFv sequence. Once digested, both plasmids were run on a 1% agarose gel along with lambda HindIII and 100 bp markers. The highlighted bands corresponded to the WT1 pUC57 vector without a scFv, and the EBNA Clone 315 scFv excised from the Tomlinson vector. These bands were excised from the gel, the DNA was purified, and ligated together to yield the EBNA pUC57 vector. The ligation products were subsequently transformed into E. coli, 10 colonies were selected at random, their plasmids were purified, and each DNA digested with EcoRI alone or EcoRI and XhoI. As anticipated, due to an inherent XhoI site within every scFv sequence derived from the Tomlison vector (with the exception of WT1 Clone 45 scFv in the context of pUC57 since the site was removed when purchased as a CAR from Genescript), the double digestion yielded three separate bands.
For the second cloning step, in which the EBNA Clone 315 CAR sequence was excised from the pUC57 vector and added to the St. Jude CAR vector, a partial digestion of the EBNA pUC57 vector using XhoI was necessary. The EBNA pUC57 plasmids isolated from the 10 colonies above were combined and digested with XhoI at room temperature for 1 minute. The reaction was quickly stopped by adding it to 4 separate wells of a 1% agarose gel and running the DNA along with uncut plasmid, lambda HindIII and 100 bp markers. The highlighted bands were determined to be the expected size of the linearized EBNA pUC57 plasmid (˜4300 bp); this linearized plasmid is a result of a random cut at either of the two XhoI sites. Subsequently, to obtain the complete CAR sequence (˜1500 bp), the linearized plasmid was isolated from the gel and digested completely with EcoRI. The resulting double and single digests were run on a 1% agarose gel along with the lambda HindIII and 100 bp markers. The highlighted band corresponded to the anticipated size of the EBNA Clone 315 CAR gene, and as a result was excised from the gel, DNA purified, and ligated to the predigested (EcoRI and XhoI) St. Jude CAR vector. After the ligation products were transformed into E. coli, 10 colonies were selected at random and their plasmids isolated. The isolated plasmids were then validated by sequencing to determine whether they contain the EBNA Clone 315 scFv sequence in the context of the CAR. In addition, the plasmids were also digested with EcoRI and run on a 1% agarose gel along with the lambda HindIII marker to validate their sizes. After demonstrating that the bands yielded the expected sizes, it was determined that the cloning was successful.
After the EBNA Clone 315 CAR was generated ( FIG. 14 ), the DNA was packaged into retrovirus and used to infect NK92MI cells in the same way as with the WT1 Clone 45 CAR. After 3-4 days of culture, the GFP expression level of the infected NK92MI cells were compared to mock-infected cells. The initial infection efficiency was approximately 24%, and after flow assisted cytometric cell sorting (FACS), the GFP-positive population was enriched to more than 90% positive ( FIG. 14 ).
Example 27
EBNA Clone 315 CAR-Equipped NK92MI Cells can Detect Cells Bearing the Specific HLA-A2-LLDFVRFMGV (SEQ ID NO: 4) Complex Via CD107a Expression
Once the NK92MI cells were enriched for EBNA Clone 315 CAR expression, they were tested for their ability to recognize the targeted HLA-A2-EBNA3C complex. As an initial readout of NK92MI activation by target cells, we assayed for cell surface expression of CD107a, a marker of NK cell and T cell degranulation (90, 91). T2 cells were loaded with 20 μM of the targeted peptide (LLDFVRFMGV (SEQ ID NO: 4)), an irrelevant peptide (YMFPNAPYL (SEQ ID NO: 76)) or no peptide. Using a 1:1 E:T ratio, the T2 cells were cocultured with EBNA Clone 315 CAR-expressing NK92MI cells in the presence of an anti-CD107a-PE conjugated antibody at 37° C. for 5 hours. As shown in FIG. 16A , NK92MI cells equipped with the EBNA Clone 315 CAR did not react to unpulsed T2 cells or T2 cells pulsed with the irrelevant peptide, showing CD107a levels comparable to those of NK92MI cells cultured in the absence of targets. On the other hand, when the CAR-equipped NK92MI cells were cocultured with T2 cells that had been pulsed with the LLDFVRFMGV (SEQ ID NO: 4) peptide, 27% of GFP + cells expressed CD107a above background levels. These results show that after scFv engineering, the CAR is able to maintain its specificity towards the targeted HLA-A2-peptide complex.
Next, in order to get a quantitative measurement of how sensitive this CAR is at activating NK92MI cells, we titrated down the LLDFVRFMGV (SEQ ID NO: 4) peptide concentration used to pulse T2 cells and measured their ability to activate the CAR-equipped NK92MI cells. As can be seen in FIG. 16B , the lower limit of response by the CAR-equipped NK92MI was at a peptide concentration of 10 nM, with a clear dose response curve beginning at the 600 nM concentration. Based on our earlier quantitation studies, this peptide concentration corresponds to approximately 25 complexes on the cell surface. Compared to the levels necessary for epitope detection using the EBNA Clone 315 scFv or scFv-Fc (200-20 nM), the CAR seems to be a more sensitive approach at detecting low levels of MHC-peptide complex on the surface of APCs using flow cytometric analysis.
While T2 cells can present any peptide of interest, BLCLs naturally present their own peptides on their MHC Class I molecules. Similarly to T2, these endogenous peptides can be replaced by simple incubation with a substitute peptide of high enough affinity. Using a 1:1 E:T ratio, HLA-A2 + (DIMT) and HLA-A2 − (6268A) BLCLs were pulsed with serum-free IMDM medium or medium containing the LLDFVRFMGV (SEQ ID NO: 4), cocultured with EBNA Clone 315 CAR-expressing NK92MI cells as discussed above, and assayed for CD107a expression using flow cytometry. Peptide pulsed DIMT (HLA-A2 + ) induced 25% of GFP + NK92MI cells to express CD107a ( FIG. 17 ), in contrast to 0.54% for peptide pulsed 6268A (HLA-A2 − ) and 1.09% for unpulsed DIMT. This data further demonstrates both peptide specificity and HLA-A2 exclusivity of the EBNA Clone 315 CAR.
Example 28
EBNA Clone 315 CAR-Equipped NK92MI Cells can Destroy Cells Bearing the Specific HLA-A2-LLDFVRFMGV (SEQ ID NO: 4) Complex Via 51 Cr Release
While CD107a expression on NK cells and T cells reflect their activation, target cell lysis can also be measured using a conventional 51 Cr cytotoxicity assay. First, to get an idea of how sensitive the 51 Cr cytotoxicity assay is with regards to killing HLA-A2-EBNA3C expressing targets, T2 cells were pulsed with decreasing concentrations of the LLDFVRFMGV (SEQ ID NO: 4) peptide at 37° C. for 3 hours and subsequently labeled with 51 Cr as described in the Materials and Methods. The labeled T2 cells were then cocultured with EBNA Clone 315 CAR-expressing NK92MI cells at 37° C. for 2 hours at a 3:1 E:T ratio. Similar to the results seen in the CD107a assay ( FIG. 16B ), EBNA Clone 315 CAR expressing NK92MI cells were able kill T2 cells in a peptide-dependent manner, with 13.2% of 2 nM peptide-pulsed T2 cells being killed compared to 10.1% with unpulsed T2 cells ( FIG. 18 ). Relative to that which can be detected using flow cytometric antibody staining, the level of sensitivity is in the order of 10-100 fold greater in favor of the CAR using two separate assays (CD107a and 51 Cr).
Next, DIMT and 6268A BLCLs pulsed with the LLDFVRFMGV (SEQ ID NO: 4) peptide (20 μM) in serum-free IMDM ( FIGS. 19A and B) were used as targets in the 51 Cr release assay. Similar to the results from the CD107a assay ( FIG. 17 ), only the HLA-A2 + DIMT BLCL were lysed by the CAR-equipped NK92MI cells ( FIG. 19A ), which could be blocked using the purified EBNA Clone 315 scFv-Fc ( FIG. 19B ). In addition, the ability to block cytotoxicity was not restricted to the scFv-Fc protein since a commercial anti-HLA-A2 (BB7.2) antibody also possessed blocking ability (data not shown). This blocking data recapitulates results seen with other MHC-restricted, peptide-specific antibodies on antigen-specific cytolytic T cells.
Although the lytic potential of the CAR-equipped NK92MI cells was clearly evident when targets were artificially pulsed with the relevant peptide, cytotoxicity against naturally processed HLA-A2-peptide complexes is of clinical relevance. Here, CAR-equipped NK92MI cells were tested against a panel of HLA-A2 + (DIMT and JG19) and HLA-A2 − (6268A and GKO) unpulsed BLCLs. While the level of cytoxicity was low, 23.0% for DIMT and 8.9% for JG19 (30:1 E:T ratio), this was highly significant when compared to 3.6% for GKO and 1.8% for 6268A ( FIG. 20A ). In addition, when the cytotoxicity assay was performed in the presence of EBNA Clone 315 scFv-Fc, the killing capacity could be reduced by approximately 46% when compared to that with an irrelevant scFv-Fc or in the absence of antibody ( FIG. 20B ). These findings demonstrate the utility and specificity of TCR-like CARs in reprogramming effector immune cells to engage antigen whose expression is below the detection limit using conventional flow cytometry.
Lastly, since both the EBNA Clone 315 CAR and scFv-Fc fusion protein have the same variable sequences used for detecting the HLA-A2-LLDFVRFMGV (SEQ ID NO: 4) complex, we decided to directly compare CAR-mediated cytotoxicity with ADCC since both approaches are currently being used independently for the treatment of cancer patients. First, the DIMT BLCL was pulsed with the LLDFVRFMGV (SEQ ID NO: 4) peptide at 20 μM in serum-free IMDM media at 37° C. for 2 hours. The pulsed BLCL was then labeled with 51 Cr and cocultured with either EBNA Clone 315 CAR or CD16(V)-expressing NK92MI cells along with EBNA Clone 315 scFv-Fc or an irrelevant scFv-Fc at an E:T ratio of 15:1 for 3 hours at 37° C. At a EBNA Clone 315 scFv-Fc concentration of 0.5 μg/ml, CD16(V) NK92MI cells were able to kill about 30-35% of cells, compared to 10-15% with an irrelevant scFv-Fc or no antibody at all ( FIG. 21 ). When the ADCC experiment was carried out using higher scFv-Fc concentrations, the cytotoxicity percentage did not change (data not shown). On the other hand, at the same E:T ratio, EBNA Clone 315 CAR-equipped NK92MI cells were able to kill 80-90% of the same peptide-pulsed target cells; and the EBNA Clone 315 scFv-Fc was included as a blocking control ( FIG. 22 ). These results demonstrate that the CAR-mediated killing involving NK92MI cells is a far more potent means of target cell lysis compared to ADCC in our setting.
Example 29
WT1 Clone 45 CAR-Equipped NK92MI Cells can Destroy Cells Bearing the Specific HLA-A2-RMFPNAPYL (SEQ ID NO: 1) Complex Via 51 Cr Release
Along with the EBNA Clone 315 CAR, we decided to test the cytolytic ability of the WT1 Clone 45 CAR in the context of NK92MI cells. First, DIMT and 6268A BLCLs were pulsed with the RMFPNAPYL (SEQ ID NO: 1) peptide (40 μg/ml) in serum-free IMDM at 37° C. for 3-5 hours. Subsequently, the target cells were labeled with 51 Cr and cocultured with the CAR-equipped NK92MI cells at 37° C. for 4 hours. Of the two peptide-pulsed BLCLs, only the HLA-A2 + DIMT could be lysed (˜70% versus ˜5% with 6268A) at a 10:1 E:T ratio ( FIG. 24 ). In addition, CAR-mediated cytotoxicity could be blocked using a commercial anti-HLA-A2 antibody by approximately 45% ( FIG. 25 ), further demonstrating specificity.
Next, we decided to tested the cytolytic capacity of WT1 Clone 45 CAR-equipped NK92MI cells against cell lines which might natively express the HLA-A2-RMFPNAPYL (SEQ ID NO: 1) complex. Due to previously published data (92), and conversations with Dr. Richard O'Reilly's laboratory here at MSKCC, researchers have demonstrated that WT1 can be constitutively activated in all BLCLs derived from EBV immortalization. More specifically, O'Reilly's group was able to show WT1 transcript in the DIMT BLCL (data not shown). As a result, we first decided to test WT1 Clone 45 CAR-mediated killing against unpulsed HLA-A2 + DIMT and HLA-A2 − 6268A BLCL. Similarly to what was seen with the EBNA Clone 315 CAR, WT1 Clone 45 CAR-equipped NK92MI cells were able to kill unpulsed DIMT at a lower capacity than peptide-pulsed DIMT. While the level of cytotoxicity was lower, ˜35% for DIMT at a 20:1 E:T ratio, it was far greater when compared to 6268A (˜5%) ( FIG. 26A ). In addition, when the cytotoxicity assay was performed in the presence of the WT1 Clone 45 scFv-Fc, the killing capacity could be reduced by approximately 43% relative to an irrelevant scFv-Fc or in the absence of antibody ( FIG. 26B ). These findings correspond well with what was seen using the EBNA Clone 315 CAR and further demonstrate the utility and specificity of TCR-like CARs in reprogramming effector immune cells to engage antigen.
Lastly, CAR-mediated cytotoxicity against two cell lines which are HLA-A2-positive and previously shown to express WT1 was tested. OVCAR-3 is a cell line established from malignant ascites of a patient with progressive adenocarcinoma of the ovary (93) and later shown to contain WT1 mRNA (94). In addition, 697 is a human pre-B cell leukemia established from bone marrow cells obtained from a child with relapsed acute lymphocytic leukemia (ALL) (95). Since then, several groups have shown that this cell line also expresses high levels of both WT1 transcript and protein (96, 97). WT1 Clone 45 CAR-expressing NK92MI cells were cocultured with 51 Cr labeled OVCAR-3 and 697 cells at 37° C. for 4 hours. CAR-equipped NK92MI cells were able to lyse approximately 20-30% of 697 and OVCAR-3 cells at a 20:1 E:T ratio, which decreased with the number of effector cells used in the assay. This data demonstrates that these two cell types are sensitive to WT1 Clone 45 CAR-equipped NK92MI cells and provides further evidence for their utility in the treatment of HLA-A2 + /WT1 + malignancies.
EQUIVALENTS
The foregoing written specification is considered to be sufficient to enable one skilled in the art to practice the invention. The foregoing description and Examples detail certain embodiments of the invention and describes the best mode contemplated by the inventors. It will be appreciated, however, that no matter how detailed the foregoing may appear, the invention may be practiced in many ways and the invention should be construed in accordance with the appended claims and any equivalents thereof.
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114. Maruo, S., B. Zhao, E. Johannsen, E. Kieff, J. Zou, and K. Takada. 2011. Epstein-Barr virus nuclear antigens 3C and 3A maintain lymphoblastoid cell growth by repressing p16INK4A and p14ARF expression. Proceedings of the National Academy of Sciences of the United States of America 108:1919-1924. | Antigen binding proteins with TCR-like paratopes, that is, with an antigen binding region specific for an HLA-A2 restricted peptide are disclosed. The antigen binding proteins encompass antibodies in a variety of forms, including full-length antibodies, substantially intact antibodies, Fab fragments, F(ab′)2 fragments, and single chain Fv fragments. Fusion proteins, such as scFv fusions with immunoglobulin or T-cell receptor domains, incorporating the specificity of the antigen binding region for each peptide are also contemplated by the invention. Furthermore, immunoconjugates may include antibodies to which is linked a radioisotope, fluorescent or other detectable marker, cytotoxin, or other molecule are also encompassed by the invention. Among other things, immunoconjugates can be used for delivery of an agent to elicit a therapeutic effect or to facilitate an immune effector function. | 2 |
CROSS-REFERENCE TO RELATED APPLICATIONS
This is a continuation of International Application No. PCT/EP2007/063032, filed Nov. 29, 2007, which is hereby incorporated by reference in its entirety.
TECHNICAL FIELD
The present invention relates to a method of preparing the connection of two fuselage sections, which are also referred to as barrels, of an aircraft.
BACKGROUND
The manufacturing process of a commercial aircraft comprises the preparing the connection of the fuselage sections. The preparing of the connection and the connection itself is known as complicated and time-consuming, because the connection has to be exact and robust. Particularly with regard to the length of the fuselage, small tolerances of a few millimeters may lead to enormous tolerances of some centimeters at the end portion of the fuselage and causes the fly characteristic of the airplane in an unknown way.
Exemplary a short description should be given about the today's method of preparing the connection of two fuselage sections of an aircraft. The sections with pre-mounted seat bars and stringers are jacked up and moved towards each other and arranged accurately using means, as for instance the seat bars or stringers and/or the width of the slit between the leading edges of the sections (circular slit with a few millimeter constant distance), till the center lines of the barrels, namely the longitudinal axis of the fuselage are in line. Small bars are clamped at the stringers to act as coupling means and to compensate the aforesaid tolerances.
At first the stringers themselves are not fixed between the last circular frame and the front edge of one section. Therefore a further compensation of the tolerances is possible. Furthermore, to compensate the manufacturing tolerances of one section it possesses a lengthwise slit. Circular brackets with calibrated bore holes (CBH) are attached at the inner side of the barrel and overlapped the front edge of one barrel by plugging fixing means as temporary rivets. The radius of the brackets is the same as the associated part of the section.
Beside the other fittings as the aforesaid small bars, the circular brackets may be attached via further fixing elements such as temporary rivets to the other barrel and a drilling template together using tack riveting.
The next process step is to drill pilot holes for every planned final bore hole which is in fact every bore hole through the skin of the sections and the brackets. Because material, such as drilling chips, could penetrate the possible spacing between the relatively thin skin and the circular bracket, it is necessary to disassemble the barrels and the fittings. After drilling the pilot holes into the skin and the circular brackets the boreholes may be deburred and degreased.
In view of the foregoing, it is at least one object of the invention to provide a less complicated and time consuming method of preparing the connection of two fuselage sections (i.e., barrels) of an aircraft. In addition, other objects, desirable features, and characteristics will become apparent from the subsequent summary and detailed description, and the appended claims, taken in conjunction with the accompanying drawings and this background.
SUMMARY
At least one benefit of the embodiments of invention is that no bore holes especially at the brackets of the fuselage sections have to be pilot drilled. High-Speed-Drilling allows a drilling in a single step. The force which acts downwards to the section or the bracket is significantly lower than during standard drilling processes which are known in this technical field. Therefore, deformation of the sections/brackets can be avoided.
The method includes, but is not limited to High-Speed-Drilling (HSD) of a group of final bore holes through an outer skin of at least one fuselage section or a coupling using one drilling template.
BRIEF DESCRIPTION OF THE DRAWING
The present invention will hereinafter be described in conjunction with the following drawing FIGURE of a schematic side view of a part of a fuselage with a first fuselage section in front and a second fuselage section used in describing the embodiments of the invention, which is not full scaled.
DETAILED DESCRIPTION
The following detailed description is merely exemplary in nature and is not intended to limit application and uses. Furthermore, there is no intention to be bound by any theory presented in the preceding background or summary or the following detailed description.
According to a first exemplary embodiment, a method is provided for preparing the connections of two fuselage sections. The method may be comprise one or all of the following steps, preferably, but not necessarily, in the following order: arranging of the sections each with one section opening towards the other section and attaching of coupling means such as brackets which contains calibrated bore holes (CBA) to at least one fuselage section and/or stringer element of at least one section. “Attaching” comprises calibrating the sections in a longitudinal axis and/or in a vertical axis of the aircraft. Detaching the fuselage sections from the coupling means and degreasing and/or deburring of the fuselage sections. Applying of sealing compound to the sections, particularly the coupling means. Fixing/riveting of the fuselage sections and the coupling means such as in a pilot drill position. Fixing of at least one drilling template via fixing means and calibrated bore holes at the fuselage sections and/or coupling means using the CBA. Drilling of a group of pilot bore holes (4.6 mm) through the outer skin of at least one barrel by using the CBA as guiding bore holes, and High-Speed-Drilling (HSD) of a group of final bore holes (4.8 mm) through the outer skin of at least one fuselage section and/or the coupling means using one drilling template. The HSD reached approximately 15,000 to approximately 20,000 revolutions per minute (RPM) and the HSD contains the lubrication and the countersinking of the bore holes. Generally pilot drilling is not necessary if the High-Speed-Drilling is used in the method.
The FIGURE shows a schematic side view of a part of a fuselage 1 with a first fuselage section 2 in front and a second fuselage section 3 . A first coupling means, in the form of a circular bracket 4 (e.g., frame) as an example, is fixed at the leading edge 5 of section 2 . Not shown are the final and pilot bore holes in the aforesaid means/sections. Both sections 2 , 3 contain further coupling means in form of stringers 6 .
It should be noted that the term “comprising” does not exclude other elements or steps and “a” or “an” does not exclude a plurality. Also elements described in association with different embodiments may be combined. It should be noted that reference signs in the claims shall not be construed as limiting the scope of the claims. Moreover, while at least one exemplary embodiment has been presented in the foregoing summary and detailed description, it should be appreciated that a vast number of variations exist. It should also be appreciated that the exemplary embodiment or exemplary embodiments are only examples, and are not intended to limit the scope, applicability, or configuration in any way. Rather, the foregoing summary and detailed description will provide those skilled in the art with a convenient road map for implementing an exemplary embodiment, it being understood that various changes may be made in the function and arrangement of elements described in an exemplary embodiment without departing from the scope as set forth in the appended claims and their legal equivalents. | A method is provided for connecting two fuselage sections. A less complicated and time consuming method was found by using High-Speed-Drilling (HSD) for a group of final bore holes through the outer skin of at least one fuselage section and/or the coupling using one drilling template preferably without any pilot drilling. | 1 |
BACKGROUND OF THE INVENTION
[0001] A wide variety of brassieres exist which are worn dependent upon the outfit, the shape, and the activity of the wearer. A brassiere is usually comprised of two cups situated on the front portion of the brassiere, for cradling the breasts of the wearer, attached to a backstrap assembly that comprises the back of the brassiere. The backstrap assembly can consist of either interlocking backstraps for posterior release and adjustment, or a single backstrap, either of which holds the brassiere in place. The cups are joined with a web of material, using interlocking materials for the web if the brassiere is detachable on its front side. Most brassieres provide for additional support by having shoulder straps leading from each cup to the backstrap assembly. There are times when the wearer will want the additional support afforded by having shoulder straps, but will not want those shoulder straps to be apparent, or will want to change the locus of support as needed based upon the wearer, the outfit, and the activity.
[0002] For example, when wearing a strapless outfit, the wearer will choose a strapless brassiere for better aesthetic appreciation of the outfit as compared with wearing the same outfit and a brassiere with shoulder straps. If the wearer were to be dressed in an evening gown with only one strap over a shoulder, it would not be aesthetic for the wearer to be wearing a standard brassiere with two shoulder straps. Similarly, if the wearer sports an outfit with a neck strap, the wearer would have difficulty finding an appropriate brassiere to wear for providing the requisite breast support in an aesthetic and discrete configuration of the brassiere. Finally, if the wearer sports an outfit made, at least in part from relatively sheer material, the wearer would not necessarily want the shoulder straps of the brassiere to show through the sheer material.
SUMMARY OF THE INVENTION
[0003] This invention is a removable brassiere strap created using a brassiere strap fastener that allows the wearer to move or remove the brassiere straps that normally sit upon each of the shoulders of the wearer. Further, if the wearer prefers to wear transparent brassiere straps, then the fasteners at the ends of the brassiere straps may be made from transparent materials, so as to give the wearer proper support using materials that are difficult to see and pass unnoticed when worn against the wearer's skin. The brassiere strap fasteners are designed so that the wearer can removably fasten the brassiere strap onto the brassiere strap fastener or mount the brassiere strap onto the fastener directly.
[0004] Brassiere straps that can be placed in virtually any conformation on a brassiere allow the wearer to arrange the brassiere so as to provide proper support while preserving the style of the outfit. For example, while wearing a dress that covers only one shoulder, the wearer can remove the brassiere strap that would normally sit upon the bare shoulder. Further, the brassiere strap can sit upon the covered shoulder, but be used to support the breast of the uncovered shoulder by looping around the neck of the wearer. Such adjustments or brassiere strap substitutions cannot be made on conventional brassieres with shoulder straps.
[0005] In another example, the wearer of a dress that loops around the wearer's neck, but which does not sit on either shoulder would not want to wear a conventional brassiere. Using this invention, the wearer could remove the brassiere straps from the backstrap of the brassiere and attach a brassiere strap to both cups and place it around the wearer's neck for support.
[0006] In one of its aspects, the invention provides a releasable fastener comprising an elongate clasping base, one end forming a slot adapted to receive a brassiere strap therethrough and a side aperture to releasably receive a brassiere clip therein. A top clasping member is pivotally connected to the clasping base and an actuating mechanism is operable between a locked position where the clasping base and top clasping member are in a clasped position and biased against each other, and an unlocked position where the top clasping member is pivotable into an open position in relation to the clasping base.
[0007] In another of its aspects, the invention provides a releasable fastener comprising an elongate clasping base with a first end forming a slot adapted to receive a brassiere strap therethrough and a side aperture to releasably receive a brassiere clip therein. A second end remote from the first end includes clasping teeth extending from a surface thereof. An elongate clasping member is pivotally connected to the clasping base at one end and another end has clasping teeth extending from a surface thereof. An actuating mechanism is operable between a locked position where the elongate clasping base and the elongate clasping member are in a biased into a clasped position with said clasping teeth of each in mating configuration, and an unlocked position where the clasping member is pivotable into an open position in relation to said the clasping member.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] [0008]FIG. 1 shows an elevational view of the cups, posterior straps, and shoulder straps of a brassiere, showing a preferred embodiment of the fasteners mounted on the ends of shoulder straps.
[0009] [0009]FIG. 2 is a side elevation view of a fastener onto which the shoulder strap can be mounted directly or through a clip.
[0010] [0010]FIG. 2 a is a cross-section of the fastener of FIG. 2 in a clasped position.
[0011] [0011]FIG. 2 b is a cross-section of a the fastener of FIG. 2 in an open position.
[0012] [0012]FIG. 3 is a perspective view of the base of the fastener.
[0013] [0013]FIG. 4 shows an elevational view of the base of the fastener.
[0014] [0014]FIG. 5 shows a top view of the base of the fastener.
[0015] [0015]FIG. 6 shows a side view of the top-clasping member.
[0016] [0016]FIG. 7 shows the view along the bottom of the top-clasping member.
[0017] [0017]FIG. 8 shows a side view of the actuating mechanism.
[0018] [0018]FIG. 9 shows a top view of the actuating mechanism.
[0019] [0019]FIG. 10 shows the rear elevational view of the actuating mechanism.
[0020] [0020]FIG. 10 a is a brassiere clip releasable connectable to a fastener of the present invention, including the embodiments of FIGS. 2, 11 or 12 .
[0021] [0021]FIG. 11 shows a perspective view of another embodiment of a fastener, a clasping portion and an actuating mechanism.
[0022] [0022]FIG. 12 shows a perspective view of the fastener embodiment of FIG. 11 including mating interlocking indentations and protrusions to interlock the actuating mechanism, with the clasping portion.
[0023] [0023]FIG. 13 is a perspective view of the fastener in FIG. 12 to be used in association with the shoulder straps of the brassiere, with the actuating mechanism removed.
[0024] [0024]FIG. 14 is a side elevational view of the fastener shown in FIG. 13.
[0025] [0025]FIG. 15 is a top elevational view of the fastener shown in FIGS. 13 and 14.
[0026] [0026]FIG. 16 is a perspective view of the actuating mechanism for the fastener shown in FIGS. 11,12, 13 , 14 and 15 .
[0027] [0027]FIG. 17 is an elevational cross-section of the actuating mechanism for the apparatus shown in FIGS. 12, 13, 14 , and 15 , taken through line A-A on FIG. 16, along axis X-X.
[0028] [0028]FIG. 18 is a cross-sectional view of the actuating mechanism for the apparatus shown in
[0029] [0029]FIGS. 12, 13, 14 , and 15 , taken through line A-A, as shown in FIG. 16 along axis Y-Y.
[0030] [0030]FIGS. 19 through 27 are elevational views shown from the front (F) and the back (B) of different configurations in which the present invention can be worn. These are meant to be illustrative only and not exhaustive.
[0031] [0031]FIG. 19 is a front and rear view of a wearer utilizing the arrangement of the invention to provide a brassiere with one brassiere strap worn around the neck.
[0032] [0032]FIG. 20 is a front and rear view of a wearer utilizing the arrangement of the invention to provide a brassiere with two brassiere straps around the neck.
[0033] [0033]FIG. 21 is a front and rear view of a wearer utilizing the arrangement of the invention to provide a brassiere with a brassiere strap over one shoulder only.
[0034] [0034]FIG. 22 is a front and rear view of a wearer utilizing the arrangement of the invention to provide a brassiere with two brassiere straps over one shoulder.
[0035] [0035]FIG. 23 is a front and rear view of a wearer utilizing the arrangement of the invention to provide a brassiere with brassiere straps in an angular configuration.
[0036] [0036]FIG. 24 is a front and rear view of a wearer utilizing the arrangement of the invention to provide a brassiere with brassiere straps in a different angular configuration.
[0037] [0037]FIG. 25 is a front and rear view of a wearer utilizing the arrangement of the invention to provide a brassiere with brassiere straps that cross over in the rear.
[0038] [0038]FIG. 26 is a front and rear view of a wearer utilizing the arrangement of the invention to provide a brassiere with brassiere straps that cross over in the anterior.
[0039] [0039]FIG. 27 is a front and rear view of a wearer utilizing the arrangement of the invention to provide a brassiere with brassiere straps that cross over in both the anterior and the posterior.
DETAILED DESCRIPTION OF THE INVENTION
[0040] Reference is made to FIG. 1 of the drawings, which shows a brassiere having cups 10 joined by material 15 . Posterior straps 20 extend from either side of cups 10 . Shoulder straps 30 are mounted to posterior straps 20 and cups 10 through fasteners 40 . The joining of fasteners 40 to brassiere straps 30 can be done removably, using clips 35 , or permanently as by looping an end of strap 30 through a strap receiving slot formed in the fasteners 40 and sewing or melting or joining the end of the strap to form an enclosed end loop of the strap passing through the strap receiving slot 47 of the fastener. FIG. 1 illustrates both methods for joining the brassiere straps 30 to the fasteners 40 .
[0041] An end of the shoulder strap 30 marked 1 of the Figure, is looped through rear slot 36 on clip 35 , and the end is then mounted to tensile sliding adjuster 38 . Clip 35 is shown in enlarged view in FIG. 10 a . Hook 37 on clip 35 is hooked into fasteners 40 through aperture 46 . The fasteners 40 that are removably joined to shoulder straps 30 are shown in FIG. 1 in the unclasped or open position.
[0042] An end of the shoulder strap 30 marked 2 is looped through rear slot 47 and is mounted to tensile sliding adjuster 38 . The fasteners 40 that are removably joined to shoulder straps 30 are shown in FIG. 1 clasped on cup 10 and posterior strap 20 .
[0043] Tensile sliding adjusters 38 allow the wearer to adjust the length and the tension of brassiere straps 30 , permitting the wearer to position shoulder straps 30 in different configurations, based upon the desired aesthetic effect and the wearer's comfort.
[0044] [0044]FIGS. 2, 2 a , and 2 b show an embodiment of fastener 40 in which a clasping base 110 has mounted a top clasping member 130 for rotation between an open and locked position. An actuating mechanism 150 is also mounted to clasping base 110 , and rotates top clasping member 130 between the open and clasped positions.
[0045] Clasping base 110 has side supports 115 onto which top clasping member 130 and actuating mechanism 150 are mounted. On side support 115 , there is an aperture 46 , through which a shoulder strap 30 can be attached using a clip 35 (see FIG. 10 a ). Side support 115 has two slots, 116 and 126 , by which, tabs 136 of top clasping member 130 and tabs 156 of actuating mechanism 150 , respectively, are pivotably held to the clasping base 110 . Also on clasping base 110 , there is rear support 125 , which forms a rear slot 47 , through which a shoulder strap 30 can be inserted and looped to provide a mount for the shoulder strap that does not require the use of a clip 35 .
[0046] The rotation of the actuating mechanism 150 in the direction of arrow A in FIGS. 2 and 2 a releases the top clasping member 130 and allows it to move away from clasping base 110 in the direction of the actuating mechanism 150 , configuring fastener 40 into an open position as shown in FIG. 2 b . Movement in the opposite direction of arrow A from the open position puts fastener 40 into the locked position of FIG. 2. As actuating mechanism 150 is rotated away from clasping base 110 in the direction of arrow A (shown as counter-clockwise in FIG. 2), tab 156 rotates within slot 126 and the actuator 155 of the actuating mechanism 150 releases top clasping member 130 . Tab 136 on top clasping member 130 is disposed within slot 116 , to provide a pivot between clasping member 130 and clasping base 110 . Fastener 40 is in the open position when top clasping member 130 is not secured by actuating mechanism 150 against clasping base 110 . When actuating mechanism 150 is rotated towards clasping base 110 , actuator 155 of actuating mechanism 150 forces top clasping member 130 into engagement with clasping base 110 . When top clasping member 130 is sandwiched between clasping base 110 and actuating mechanism 150 , the fastener 40 is in the locked position, as shown in FIGS. 2 and 2 a.
[0047] In a preferred embodiment, top clasping member 130 and clasping base 110 have clasping teeth 131 and 111 respectively. The clasping teeth 131 and 111 provide for better retention of the material of the brassiere disposed between top clasping member 130 and clasping base 110 when the fastener 40 is moved from the open to the locked position.
[0048] A perspective view of clasping base 110 is shown in FIG. 3. Side supports 115 and rear support 125 are moulded for retaining top clasping member 130 and actuating mechanism 150 through slots 116 and 126 respectively. Shoulder strap 30 can be inserted through rear slot 47 for joining fastener 40 to shoulder strap 30 . Alternatively, shoulder strap 30 can be mounted to rear slot 36 of a clip 35 and hook 37 of clip 35 can be inserted through side apertures 46 that open into rear slot 47 . Both of these configurations are shown in FIG. 1. Also shown on clasping base 110 are clasping teeth 111 that are interspersed with a complementary mating set of clasping teeth 131 located on top clasping member 130 , shown in FIGS. 5 and 6. Protrusions 118 line the inside walls of side supports 115 and are adapted to create a spring effect to push top clasping member 130 towards either a fully open or fully closed position, depending on the position through which the wearer has rotated top actuating member 150 .
[0049] [0049]FIG. 4 shows a continuous aperture 46 passing through the entire length between side supports 115 and rear support 125 , for insertion of hook 37 into fastener 40 . FIG. 4 also shows, with dashed lines, rear slot 47 which transcends the entire thickness of rear support 125 , to permit direct insertion of shoulder strap 30 into fastener 40 .
[0050] [0050]FIG. 5 shows a top view of clasping base 110 , onto which top clasping member 130 is closed. Rear support 125 and side supports 115 have aperture 46 , shown in dashed lines, extending continuously through the entire width of clasping base 110 . Aperture 46 is of sufficient diameter for the attachment of hook 37 to fastener 40 . Rear slot 47 is shown centred between side supports 115 , with a length and width which corresponds approximately to the thickness and width respectively of the shoulder strap to be inserted. Side supports 115 and rear support 125 are shown as moulded from one common piece of material, however, they can also be discrete pieces of material that are mounted together on clasping base 110 . FIG. 5 also shows groove 127 for receiving latches 137 on top clasping member 130 .
[0051] [0051]FIG. 6 shows an elevation view of top clasping member 130 , while FIG. 7 shows a view of the clasping surface. Top clasping member 130 has clasping teeth 131 , and tabs 136 for insertion into slots 116 on clasping base 110 . Slit 132 provides flexibility and greater freedom of movement in top clasping member 130 , making tabs 136 easier to insert into slots 116 . Latches 137 slide into groove 127 and provide an axis of rotation for top clasping member 130 . Slit 132 and the insertion of latches 137 into groove 127 on clasping base 110 endows top clasping member 130 with a spring-like quality tending to push top clasping member 130 away from clasping base 110 .
[0052] [0052]FIGS. 8, 9 and 10 show actuating mechanism 150 , which has tabs 156 for mounting actuating mechanism 150 pivotally about tabs 156 into slots 126 . Actuating mechanism 150 is also comprised of lever 152 and actuator 155 . The wearer moves lever 152 to actuate the clasping or the opening of fastener 40 . Actuator 155 interacts with top clasping member 130 to favour either the open or clasped position, depending on the position of lever 152 .
[0053] Beginning from an open position, lever 152 is pressed towards clasping base 110 , such that actuator 155 comes into contact with top clasping member 130 and forces top clasping member 130 against clasping base 110 . When lever 152 forms an angle of about 20-30 degrees with clasping base 110 , there is an inflection point where actuator 155 applies as much force as it can to top clasping member 130 against clasping base 110 . As lever 152 moves past the inflection point to close the fastener 40 in the clasped position, actuator 155 is still compressing top clasping member 130 , but not as forcefully as it was at the inflection point. Once lever 152 moves past the inflection point as the fastener is being clasped, top clasping member 130 uses the spring-like quality imparted by the insertion of latches 137 into groove 127 to push actuator 155 towards rear support 125 . As a result of this interaction between actuator 155 and top clasping member 130 , lever 152 springs onto top clasping member 130 , holding top clasping member 130 in the clasped position. Conversely, when the fastener is configured to the open position, as the lever 152 is moved away from clasping base 110 , actuator 155 applies force to top clasping member 130 until the inflection point is reached. Once passed the inflection point, the actuator 155 applies less force to top clasping member 130 , and top clasping member 130 springs against actuator 155 such that lever 152 moves to the open position.
[0054] In another preferred embodiment of fastener 40 , the actuating mechanism 150 and top clasping member 130 can be incorporated into a combined clasping actuator, using an inflection point on the clasping base 110 for creating tension to hold the fastener open or clasped, as the wearer requires.
[0055] [0055]FIG. 10 a shows a brassiere clip having a hook 37 adapted to be releasably inserted into the fastener of FIGS. 2, 11 or 12 . The clip has a rear slot 36 through which an end of a shoulder strap 30 may pass for mounting the clip 35 on the strap 30 . The clip has a hook 37 , which releasably engages fastener 40 through aperture 46 of the clip of FIG. 2 or 246 of the clips of FIGS. 11 or 12 .
[0056] [0056]FIGS. 11 through 18 show another embodiment of the fastener 40 that can be used as shown in FIG. 1. Referring to FIGS. 11 and 12, the fastener is comprised of two elements, fastener 240 and actuating mechanism 250 . Fastener 240 has a clasping base 210 , and a top clasping member 230 that are integrally molded in one piece on support 220 . Support 220 has integrally molded to it two side supports 215 which bend towards one another at approximately right angles from side support 215 to form two rear supports 225 , spaced apart by a thickness that corresponds to the thickness of shoulder strap 30 . The manner in which the rear supports 225 are formed are such that they form a rear slot 247 into which shoulder strap 30 can be inserted. In another embodiment, rear supports 225 can be moulded together and form a continuous rear slot 247 . Side support 215 has a continuous aperture 246 that is co-extensive with rear slot 247 . In an embodiment where shoulder strap 30 has a clip 35 at its terminal ends, the hook 37 of clip 35 can pass through aperture 246 to hook onto the side supports 215 .
[0057] Top clasping member 230 and clasping base 210 are operable between an open and clasped position. When in the clasped position, clasping teeth 231 on the inner surfaces of top clasping member and clasping base 210 rest on indented supports 232 located opposite the clasping teeth on the facing clasping member. The clasping teeth 231 and indented supports 232 are arranged such that each clasping tooth 231 has a corresponding indented support 232 upon which it rests when top clasping member 230 and clasping base 210 are in the closed position.
[0058] Actuating member 250 slides along support 220 and can be moved by sliding along support 220 over top clasping member 230 and clasping base 210 . Actuating mechanism 250 is movable between an open position on support 220 and a clasped position over top clasping member 230 and clasping base 210 . As actuating mechanism 250 is slid into the clasped position, the actuating mechanism forces top clasping member 230 and clasping base 210 together in a single motion. When a piece of material is inserted between the top clasping member 230 and the clasping base 210 , the clasping teeth 231 catch the material and hold it securely against indented supports 232 located opposite the clasping teeth 231 . When actuating mechanism 250 is moved into the open position onto support 220 , the pressure it applied to close the top clasping member 230 and the clasping base 210 is removed such that the two clasping members can separate and release the material wedged between the clasping members.
[0059] In a preferred embodiment, the top clasping 230 has a plurality of indentations 237 that correspond to a protrusion 252 on actuating mechanism 250 as seen in FIGS. 17 and 18. Protrusion 252 secures actuating mechanism 250 from motion by interlocking with an indentation 257 on top clasping member 230 . Because the thickness of the material to be clasped can vary, the actuating mechanism 250 can be secured at multiple positions along top clasping member 230 . Each indentation 257 that is located further from support 220 towards the free ends of top clasping member 230 and clasping base 210 provides for a tighter clasp setting when actuating mechanism 250 interlocks with the indentation 257 . A tighter clasp setting holds finer fabrics while thicker fabrics can be held using a less tight clasp setting.
[0060] In another preferred embodiment, brassiere straps 30 are made from transparent or translucent materials and may be tinted with various colours, either transparently or translucently or opaquely, as required by the look that the wearer wishes to achieve. Similarly, the wearer may desire to have fasteners 40 that are also virtually invisible to observers. The constituent elements of fastener 40 can be made from transparent or translucent materials such as nylon, polyurethane, polyethylene terephthalate, or acetal and may be tinted with various colours, either transparently or translucently or opaquely, so as to be virtually invisible to observers. | The invention comprises a fastener mountable on a brassiere strap, either removably or permanently. A brassiere strap mounted on the fasteners can be removably affixed to a location on the posterior strap assembly and a location on the anterior cups of a brassiere. Use of the fasteners permits adjustment of the brassiere straps into a plurality of different arrangements, depending upon the shape, outfit and activity of the wearer. The brassiere straps and fasteners can be made of transparent or translucent materials which may be color tinted so as to appear virtually invisible against the wearer's skin. The brassiere straps can also be removed from a brassiere altogether. | 0 |
This application claims priority and is a continuation of Ser. No. 12/315,209 Filed Dec. 1, 2008, now U.S. Pat. No. 7,678,828 which is a continuation of PCT application serial number PCT/US2007/013781 filed 12 Jun. 2007, which claims priority of U.S. provisional application Ser. No. 60/813,288 filed 13 Jun. 2006.
GOVERNMENT INTEREST
The invention described herein may be manufactured, used and licensed by or for the U.S. Government.
BACKGROUND OF THE. INVENTION
1. Field of the Invention
The methods of the present invention provide a unique and superior formulation of artesunic acid for parenteral injection and for the manufacture of the formulation under sterile conditions. The methods described herein provide a demonstrably sterile, non-pyrogenic product which dissolves rapidly with no frothing or caking, yielding a clear, conveniently prepared solution the attending physician may administer with confidence. The formulation that is prepared by the methods of the invention is especially suitable for the treatment of severe and complicated malaria.
2. Brief Description of Related Art
Although malaria affects about 250 million people and kills one to two million children each year, the pharmaceutical industry has shown little interest in developing new or manufacturing established antimalarial drugs not only because risks are significant, but the returns on investment are so low.
Currently, the most promising and most rapidly acting antimalarial drugs are derivatives of artemisinin (qinghaosu) obtained from qinghao or sweet wormwood ( Artemesia annua ); these drugs have been developed and manufactured in China. Three compounds of the qinghao family have been used: the parent artemisinin and two of its more-active derivatives: a water-soluble hemisuccinate, artesunate (AS), and an oil-soluble ether, artemether (AM). Both derivatives are metabolized to a common biologically active metabolite, dihydroartemisinin (DHA). Although this facile conversion (hydrolysis) to DHA contributes to the AS rapid antimalarial activity, it also limits the choices of practical AS dosage formulations.
Artesunic acid is also known to be effective in the treatment of severe (neuropathic) malaria, Artesunate versus quinine for treatment of severe falciparum malaria; a randomized trial , Dondorp, et al; Lancet, vol. 366, pages 717-725, Aug. 27, 2005, incorporated herein in its entirely by reference. However, Artesunic Acid is an intrinsically unstable compound, susceptible to decomposition by heat, radiation, and virtually any aqueous solution. Prior studies have confirmed the breakdown of artesunate in aqueous solutions.
AS has been used for injection with good results. However, there are drawbacks of the current commercially available AS dosage form. It is a two-component product consisting of a dry-fill powder of sterile artesunic acid in a vial and a sterile 5% sodium bicarbonate solution in an ampoule. This product, “Artesunate For Injection”, is manufactured by Guilin Pharmaceutical Factory, Guangxi, China. This presently used formulation, when dissolved in the supplied bicarbonate buffer solution, results in fizzing and incomplete solution so that the concentration (dose) to be delivered may be uncertain.
The formulation of artesunic acid mentioned above is manufactured in China, and prepared by an undivulged method which results in a product of poor dissolution characteristics, and which froths and cakes upon introduction of the dissolution medium (5% bicarbonate). As the AS dissolves, carbon dioxide is evolved and trapped in the small volume of the closed vial. The formed gas bubbles carry un-dissolved AS particles throughout the vial, thereby reducing contact between these particles and the dissolution medium and lengthening the time needed to completely dissolve the AS. Moreover, this phenomenon reduces the investigator's ability to see if the solution is complete so the next preparation step, which is to dilute the AS/bicarbonate solution with 5 mL of sterile 5% glucose solution, can begin. These delays can unduly lengthen the overall solution preparation time, resulting in a shorter time period over which the prepared solution can be administered.
Further and most importantly, the product coming from China is not manufactured under the U.S. Food and Drug Administration's current Good Manufacturing Practice (cGMP).
Therefore, it is an object of the present invention to provide an AS product and a method for preparing an AS product that dissolves quickly, thoroughly and does not cake or fizz upon dissolution.
It is another object of the present invention to prepare an AS product that does not require an additional step of diluting with glucose and is immediately usable upon dissolution.
Another object of the present invention is to develop a method for the production of an artesunic acid solution for the intravenous or intramuscular treatment of malaria that is sterile and manufactured under current Good Manufacturing Practice (cGMP) as required by the U.S. Food and Drug Administration.
Another object of the present invention is to sterilize artesunic acid powder without decomposition.
Another object of the invention is to prepare an artesunic acid product that has a shelf life of two years.
These and other objects will become apparent upon further reading of this application.
SUMMARY OF THE INVENTION
The invention is a method for the manufacture of an intravenous or intramuscular formulation of artesunic acid. First the artesunic acid powder is sterilized with ethylene oxide and placed into a sterile container. Nitrogen is used to purge water vapor from the container, after which the container is hermetically sealed. When used, the sterilized powder is dissolved in sterile sodium phosphate buffered solution to produce a solution suitable for intravenous or intramuscular administration. The sodium phosphate buffered solution dissolves the artesunic acid powder without caking or frothing, resulting in an improved drug product. The invention also relates to the formulation and a method of treating a patient with severe and complicated malaria.
BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 is drug manufacturing flow diagram;
FIG. 2 is the chemical structure of α-Artesunic Acid.
DETAILED DESCRIPTION
The AS parenteral dosage form must be sterile and not produce CO 2 when the AS dissolves. To avoid CO 2 evolution, we used a non-carbonate-containing, physiologically compatible basic medium. We also manufactured our drug product under cGMP.
Dissolution Medium
The dissolution medium is sodium phosphate buffered solution.
In addition to avoiding the production of gas, the dissolution medium must rapidly dissolve the AS, produce a solution in which the dissolved AS is sufficiently stable, and yields a solution of physiologically acceptable pH and osmolality. After many trials and errors, we found that a 0.30±0.05 M, pH 8.0±0.3 sodium phosphate solution meets all of the above requirements and is preferred. Slight variations from these values are acceptable.
The solute in the dissolution medium has been identified as sodium phosphate by spectral and chromatographic evidence. The average phosphate concentration is 0.30 plus or minus 0.05 M. The average solution volume is 11.0 plus or minus 0.5 mL. The average solution pH is 8.0 plus or minus 0.3.
Preparation of the 0.30M, pH 8.0 sodium phosphate solution, following a USP procedure, was straightforward and under cGMP. Sterile phosphate solution, 0.30 M, pH 8.0, is manufactured by mixing appropriate weights of monobasic and dibasic sodium phosphate in distilled water to a molarity of 0.30 M and pH of 8.0. The phosphate solution is then sterilized by filtration through a 0.22μ filter into 20 mL vials (12.2 mL/vial). The vials are sealed and then stored at room temperature.
Sterility of the product, achieved through sterile filtration of the phosphate solution and autoclave of the filled, sealed vials, was accomplished smoothly by Afton Scientific Corporation, Charlottesville, Va. 22902. After having met USP requirements for identity of the product, product sterility, endotoxin, solution concentration, volume, pH, osmolality, and particulates, 10,900 vials of this medium were labeled Afton Batch 57804, assigned WR135946; BR18064, and designated as Component Two of our AS dosage form. The USP procedure is found in 2005 USP 28/NF 23, p 2855; Composition of Standard Buffer Solutions, incorporated herein by reference.
Active Component
The active component is Artesunic Acid (AS), 110 mg/vial, SRI Batch No. 14462-16, from SRI International, Menlo Park, Calif.
The Chemical Abstracts (CA) Index name for artesunic acid is: butanedioic Acid, [3R-(3α,5a,6,8a,9α,10α,12,12a R*)]-mono(decahydro-3,6,9-trimethyl-3,12-epoxy-12H-pyrano[4,3-j]-1,2-benzodioxepin-10-yl)ester.
The CA Registry Number is 88495-63-0, and the molecular formula is C 19 H 28 O 8 . The formula weight of α-artesunic acid is 384.43 g/mol. This name also defines the stereochemistry at C-10 which, according to the CIP convention, is based on the priority of groups attached to C-10. The 10α-designation refers to the O-succinal group oriented back or toward the peroxide bridge. The 10-designation refers to the O-succinal group oriented away from the peroxide bridge. The molecular formula, C 19 H 28 O 8 , corresponds to a molecular composition of C, 59.36%; H, 7.34%; and 0, 33.29%; and a molecular weight of 384.43. α-Artesunic Acid is shown in FIG. 2 .
The formulation development of the active component AS requires sterilization of the bulk drug. For a sterilization process to be acceptable, not only sterility of the bulk chemical must be shown, but the process must not alter the physical or chemical nature or the stability of the material. The high purity AS bulk drug, a finely milled, white crystalline powder manufactured by Knoll AG, Listal, Switzerland was used.
An acceptable EtO treatment cycle was developed and employed as follows:
Sterilization of Bulk Artesunic Acid
The bulk AS was sterilized before dry fill. Gas sterilization was used. Below are the salient points of the method and the determinations for sterility and pyrogenicity.
Artesunic Acid is treated for one hour at 102 degrees Fahrenheit and 100% humidity. The chamber is evacuated and ethylene oxide is introduced and maintained at constant pressure and 102 degrees Fahrenheit for four hours. The sterilant cycle is stopped; the chamber is evacuated and washed twice with nitrogen and once with air, all at 102 degrees Fahrenheit. Slight variations of this sterilization method are possible. A sample of treated AS is chromatographed. Chromatograms for both treated and untreated AS are identical. AS is stable under the conditions of treatment. Samples are tested for residual ethylene oxide, ethylene chlorohydrin and ethylene glycol. Neither ethylene chlorohydrin nor ethylene glycol was detected. Ethylene oxide was detected but at levels well below the FDA proposed limit. A microbial limits test was performed and validated to determine the inhibitory properties of AS. The test was negative. AS has no inhibitory properties in this test. (USP 27 <61> & <71>). Sterility tests were performed to discover the possible presence of bacteria, fungi, and spores. Samples were doped before treatment with a spore strip, bacteria, and fungi. No colony forming units were found in any test. The treated material is sterile. (USP 27 <71>). The Limulus Amebocyte Lysate test was performed to determine the endotoxin levels in the treated AS. Endotoxin levels were below the detectable level in the to treated AS. (USP 27 <85>)
Ethylene oxide is an effective sterilant for bulk artesunic acid. Results from validated sterility tests on sterilized artesunic acid meet USP requirements for sterility testing. Sterilized artesunic acid also meets USP requirements for endotoxins.
The EtO-treated AS was dry filled into sterile vials. The best mode for this purpose was to use a portable, manually operated powder dispensing machine was purchased from M&O Perry Industries, Corona, Calif. 92880. Owing to the propensity of the AS bulk drug to clump and cling to the metal surface of the machine, characteristics that prevent both complete filling and complete discharge of the machine loads, the machine was fitted with a plastic liner that reduced the clinging and enabled quantitative discharges. The installation qualification (IQ)/operation qualification (OQ)/and performance qualification (PQ) were performed to qualify the filling machine for cGMP manufacturing. The Model LM-14 is a compact, portable bench top unit complete with carrying handle. It is an ideal machine for small fill weight, low volume applications. Other filling machines exist which are suitable for large operations.
Pre-cleaned and sterilized 20-mL vials, sterilized gray butyl rubber stoppers and flip-off aluminum seals were purchased. In a class 100 room, under laminar flow, the vials were filled in a glove box with EtO-treated AS. Scheduled weight checks were performed to ensure the filled weights met specifications. The filled vials were stoppered, sealed, and tested for release. After meeting requirements for sterility, identity, purity, content uniformity, and after constitution in sodium phosphate buffer, for solution pH, osmolality, and particulate counts, 5,500 of the filled vials were labeled SRI Batch 14462-16, assigned WR256283:BR29487, and designated as Component One of our AS dosage form.
Analytical Methods of Specifications for Sterile Intravenous Artesunate (110 mg/vial) Tests Analytical Methods Specifications Appearance Visual Fine crystalline powder Color Identity Visual White to almost white IR Conforms to Must comply Reference Spectrum HPLC HPLC SRI TM 1900.200 Must comply Assay (HPLC) HPLC 98.0 to 102.0% calculated on water-free basis pH SOP SRI 004.009 7.2-7.7 Particulate USP 788>, small volume No More Than (NMT) 6000 Matter in injections particles of size 10 μm/vial. Injections NMT 600 particles of size 25 μ/vial. Uniformity of USP 905>, Solids None outside 88-132 mg/vial, Dosage Units in Single Unit RSD of 10 vials ≦6.0% in Containers Level 1; if fail, go to Level 2. Sterility USP 71> Sterile Bacterial USP 27 through 35 EU/mL Endotoxins, Sup 85> LAL, Kinetic
Placebo
The selection of a material for the AS placebo was based on a likeness in appearance and physical characteristics to that of the AS dosage form, in addition to being biologically inert. The placebo for the AS Dosage Form was Mannitol, 200 mg/vial.
A large number of possible placebos were investigated. The two final candidates were mannitol and glucose, with the former having a slight edge. Because the particle size of the commercially available USP mannitol was larger than that of the AS bulk drug, the mannitol was milled and sieved to match the size and appearance of the AS powder prior to sterilization. Sterilization by irradiation initially looked promising, but after two weeks on the shelf the irradiated mannitol became discolored. Ultimately, treatment with EtO proved successful, and the sterilized mannitol was dry-filled into the same type of glass vials as the active material and processed identically. Because the density of our mannitol was nearly twice that of the AS bulk drug, the filled placebo mass was nearly twice that of the active, to maintain comparable filled volumes. After having met requirements on content uniformity, identity, and purity, and after constitution with phosphate, for solution pH, osmolality, and particulate counts, 2,500 vials of the placebo were labeled SRI Batch 14462-28 and designated WR016506:BR29487. To maintain anonymity, a common label, identifying both the AS and Placebo, was used for vials of the active as well as vials of its placebo.
In Phase I clinical trials the placebo was ethylene oxide treated mannitol, exhibiting the same appearance and dissolution characteristics as the Active Pharmaceutical Ingredient (API). The placebo was manufactured by SRI International. All clinical materials are stored, maintained, and shipped by the repository contractor (monitored and managed by The Department of Chemical Information). The repository contractor also prepares the double-blinded samples of artesunic acid or placebo for clinical use under guidance from the Department of Chemical Information. The placebo has provided an acceptable control for the recently completed phase I clinical trials.
Analytical Methods and Specifications for Sterile Placebo for Injection (200 mg/vial) Test Analytical Methods Specifications Appearance Visual Fine crystalline powder Color Visual White to almost white Absence of I.R. None detected Artesunic Acid Mannitol Content USP (Identity) Passes Ethylene Oxide USP 71> 200 ppm Residual Ethylene NV SOP 12C-25 120 ppm Chlorohydrin (ECH) Residual USP 71> Microbial growth is Sterility not observed Uniformity of USP <905>, solids None outside 88-132 Dosage Units in Single Unit mg/vial, RSD of 10 vials ≦6.0% Containers in Level 1; if fail, go to Level Particulate USP <788> No More Than (NMT) 6000 Matter in particles of size 10 μm/vial. Injections NMT 600 particles of size 25 μ/vial.
Dosage
A typical dosage of α-artesunic acid for parenteral administration is 10 mg/mL for a 10 mL injection. 110 mg is the unit dose for manufacture. Typically, using a sterile syringe, 11 mL of sterile Phosphate buffer for injection will be added to the 110 mg artesunate vial and the vial swirled for about 4-6 minutes for full dissolution. Dosing is 1-4 mg/Kg body weight for intravenous administration with the possibility of up to 8 mg/Kg in some cases. Preferred dosing is 2-3 mg/Kg body weight for intravenous administration for three days. A drip bag is also suitable for administration of the dose. A dosage of 50 mg/mL is suitable for IM injection. IM treatment will be in the range of 1-5 mg/Kg body weight. Give dosage one to two times per day for 3 days for IM. Because the present inventors use a phosphate buffer solution, they are able to obtain a higher concentration of AS for injection than that which can be obtained with the 5% glucose dilution medium required by the Guilin formulation.
Discussion
The cGMP-manufactured α-artesunic acid parenteral dosage form of the invention offers several advantages over current, commercially available version(s) of Artesunate drug.
1. The cGMP-manufactured sterile dissolution medium, a 0.30 M, pH 8.0 solution of sodium phosphate, completely dissolves the α-artesunic acid in 2-3 min, requiring only gentle swirling. This rate of dissolution is several fold faster than that found for the Guilin product, following its directions for preparation given in its package insert. 2. Because the dissolution of AS in phosphate is not accompanied by gaseous evolution, as in the case where bicarbonate is used, determining solution completeness is readily achieved. 3. The solution prepared in phosphate is ready for administration, as no further preparation is required. The Guilin product, on the other hand, requires an additional step of dilution of the AS/bicarbonate solution with 5 mL of 5% glucose, which also must be sterile. 4. The pH of our 10 mg AS/mL solution in phosphate is 7.2, whereas that for 10 mg AS/mL solution in bicarbonate/glucose is 7.9, a solution pH that is higher than ideal for parenteral administration. 5. The osmolality of our 10 mg AS/mL solution in phosphate is 320 and that for the 10 mg AS/mL solution in bicarbonate/glucose is 410, a value also higher than ideal for parenteral administration. 6. The phosphate buffer solution of the GMP manufactured formulation allows AS concentrations high enough for effective IM treatment.
Although hydrolysis of AS in phosphate or bicarbonate/glucose begins almost immediately upon dissolution, the rates of decomposition in the two media are comparable. After two hrs at ˜24° C. the solutions were still visibly clear and therefore still can be administered.
In keeping with US FDA requirements, vials of the phosphate vehicle, the AS, and the placebo are undergoing accelerated and shelf-life stability studies.
Efficacy in Trials:
An Investigational New Drug Application (IND-64769) on this drug product has been filed with the FDA and has been approved for use in clinical trials. Phase Ia Safety and Tolerance single dose clinical trials have been concluded and were successful.
Phase Ia Safety and Tolerance of GMP Formulation
Phase Ia is a single dose double-blind placebo-controlled, randomized study to evaluate the safety and tolerance of the GMP formulation of intravenous artesunate. The study has been completed successfully as is necessary to proceed to Phase IB and Phase II trials. Phase Ib and Phase II trials are in progress.
Phase Ib Safety, Tolerance and Pharmacokinetics/Pharmacodynamics of GMP Formulation
A Phase 1b is a double-blind, placebo-controlled, randomized multiple dose escalation study to evaluate the safety, tolerance, and pharmacokinietics/pharmacodynamics of GMP formulation of intravenous artesunate in healthy human subjects in 3 doses using a dose escalation format using a placebo control. An objective is to determine the safety of multiple dose administration of escalating doses of artesunate that bracket the anticipated compassionate use dose of 2.4 mg/kg by measuring adverse events (AE) and cardiovascular responses (heart rate (HR), blood pressure (BP), and electrocardiogram (ECG)). Another objective is to determine the safety and tolerability of the compassionate use of 3 doses of artesunate in escalating doses of 0.5, 1.0, 2.0, 4.0, and 8.0 mg/kg with placebo control. The primary and secondary outcomes are to assess AE and hemodynamic and cardiac responses (BP,HR, ECG) and to determine pharmacokinetic parameters of artesunate and its major metabolite DHA as well as to assess preliminary dose-toxic response.
The study design is as follows: Phase I, randomized, double-blind, placebo-controlled trial using multiple ascending doses of intravenous artesunate to determine its safety, tolerability and pharmacokinetics in healthy male and female subjects. Subjects will be screened within 21 days of dosing. At the screening visit, subjects will undergo baseline VS, PE, CBC with smear, differential and indices, reticulocyte count measured by flow cytometry, haptoglobin, COAGs, Chem, UA, urine drug screen, urine HCG and medical and medication history. Eligible subjects will be scheduled for a 6-hour outpatient visit for pre-dose ECGs and VS done to approximately match dosing schedule on Day 1. On Day 0, subjects will be admitted to the CPU to begin the inpatient phase of the study. Subjects will have a brief physical and review all procedures for the inpatient stay. On Day 1, pre-dose, VS and ECG will be performed. Subjects then will receive IV study drug or placebo. Subjects will be closely monitored by evaluating hemodynamic measurements, periodic ECGs, and assessment of spontaneously reported AEs. Blood will be drawn for blood count and chemistry analysis within 12 hours of the first and last doses. PK will be drawn at designated times after each dose administered. On Days 2 and 3 subjects will receive their second and third doses, respectively, of study drug or placebo followed by close clinical monitoring and laboratory measurements as described for the first doses given. Subjects will be discharged 24 hours after the third dose of drug or placebo and followed as outpatients on Days 7, 10, and 15. The study population will consist of 40 healthy male and non-pregnant female adults given artesunate GMP manufactured for injection intravenously.
The duration of the study will be a screening of up to 21 days; 5 days (four nights) inpatient and 3 outpatient visits (last visit day 15) per patient.
Phase II Trials:
In Phase II trials, the artesunic acid parenteral dosage form of the invention was given intravenously to human subjects in Africa to treat malaria. In trials in Africa, COL Peter Weina, Chief, Department of Pharmacology, Walter Reed Army Institute of Research has reported 30 adult male and female volunteer patients with uncomplicated malaria have been successfully treated using the treatment regimen as outlined in this application. Successfully treated is defined as safely clearing P. falciparum malaria parasites from the blood. Patients were given a single dose of 1-4 milligrams per kilogram body weight in the form of an injection through an IV catheter (a tube with a needle attached) once a day for 3 days in a row. There were no adverse effects from the GMP IV treatment of the artesunate of the invention. The single adverse effect was with the standard-of-care positive control drug Malarone.
Stability Studies
Six thousand dry-filled vials of formulated artesunate for clinical use have been packaged. One thousand of the vials have been reserved for long-term stability testing under various conditions, including elevated temperatures and humidities, to test the integrity and durability of the packaging system. As packaged for clinical use, 20 ml vials have been dry-filled with 110 mg of ethylene oxide sterilized artesunate, stoppered, and sealed. Stability studies at Knoll have shown at least two years stability for bulk artesunic acid stored under nitrogen @ 25° C.
The sterilized bulk drug of the invention has been tested and is still undergoing stability studies. The sterilized bulk drug has shown no evidence of degradation for 20 months at 25° C. The stability studies are still ongoing.
Having generally described this invention, a Further understanding can be obtained by reference to certain specific examples which are provided herein for purposes of illustration only and are not intended to be limiting unless otherwise specified.
EXAMPLES
Example 1
GMP Formulation and Packaging
Upon receipt of the accessible portions of the European Drug Master File (DMF) for artesunic acid from Knoll, the inventors compared their analytical protocols for artesunic acid to those used in the DMF. The DMF method used by Knoll is as follows:
Validation of an HPLC-Based Assay for AS
HPLC was performed using the following conditions:
LC system Solvent Delivery Waters 600 Pump System Controller Injector Waters 717+ Auto Sampler Detector Waters 996 Photo Diode Array (PDA) Quantitation Software Empower, Build Number 1154 Method Conditions Column YMC ODS-AQ 2 250 mm Length × 4.6-mm ID, 3 μm Mobile Phase 35:65 A:B where A = 0.01M potassium dihydrogen phosphate, pH 3.8, and B = Acetonitrile Flow Rate 1.20 mL/min; pressure~2400 psig Injection Size 30-μL Run Time 20 min Detection UV @ 205 nm
The reference solutions (n=5 each) were prepared by accurately weighing between 3.472 to 15.977 mg of the reference and dissolving each in 1.00 mL of acetonitrile. A series of 30-μL injections were made to deliver 104.2 to 479.3 μg of reference on column for assay.
Calculations (Apply to Both Reference and Sample)
The mass of sample on column (m x , μg) was calculated using equation one (EQ. 1)
m x =W x ×( V 1 /V x ) Eq. 1
where, W x is the sampled mass (mg) of the reference or sample (S) as weighed, V x is the volume of solvent (1.00 mL acetonitrile) used, and V 1 is volume of solution injected (30 μL). An area to mass on column response factor (RF A ) was calculated for the reference standard using equation two (Eq. 2)
RF A =( A R /m R )×(100%/ P R ) Eq. 2
Where, A R is the reference peak area, and P R is the reference purity (>99%) 3 . Sample peak area data was used in equation three (Eq. 3) to calculate the mass (m s ) of the sample,
m s =A S ×(100%/RF A ) Eq. 3
where A s is the sample peak area.
Duplicating all the experimental conditions used by Knoll, the inventors confirmed the results of its previously validated HPLC assay. Upon validation of the imported Knoll assay, it was adopted as one of the assays to be used by the inventors to confirm the identity of artesunic acid samples and to test the purity of such samples. The major advantage of the Knoll method was lowering the LOD from 2 ug to 0.075 ug on column and decreasing the assay time from 16 minutes to 8 minutes. The major disadvantage is its inability to determine AS in phosphate. Precision, linearity, quantation, and accuracy were comparable for both methods.
The inventors verified the identity and determined the purity of three samplings of WR256283; BQ38641, (Knoll Lot 2.03). This was the milled sample of the bulk Knoll drug substance used in formulation of the injectable artesunic acid for clinical trials. The three samples were taken to confirm the identity and uniformity of the received material (Sample A from the top of the container, Sample B from the middle of the same container, and Sample C from the bottom of the container). They were compared to a reference sample received Jun. 29, 2001 (WR256283; BP18288) using a number of analytical tests including, but not limited to, Fourier Transform Infrared Spectroscopy, Proton Nuclear Magnetic Resonance Spectroscopy, Elemental Analysis, High Performance Liquid Chromatography, Thermogravimetric Analysis, Residual Solvents by Gas Chromatography, and Inductively Coupled Plasma. The samples were confirmed as being identical samples of artesunic acid. Purity was determined with an HPLC-based assay using the external standard method, with a known reference purity of >99%. HPLC results confirmed sample purity was 99.3 plus or minus 0.3%. Residual solvents in the Knoll material include heptanes (0.09%) and ethyl acetate (0.04%), plus trace amounts (<0.01%) of methanol and ethanol. Lead was not found.
SRI verified that an ethylene oxide sterilization treatment (4 hours at 102 degrees F.) does not degrade artesunate; the treated material meets USP requirements for sterility. The EtO treated sample was purged with nitrogen to remove residual ethylene oxide. Subsequently, bioburden, bacteriostasis, fungistasis, and endotoxin tests were performed to validate the sterility treatment method. Tests for ethylene oxide derivatives were negative and the residual EtO was found to be well below the FDA recommended levels. Tests for artesunate breakdown products, including dihydroartemisinin, were similarly negative. Results from validated bioburden and LAL tests on sterilized artesunate met USP requirements for sterility and endotoxins. The average chromatographic purity after ethylene oxide treatment was found to be 99.9 plus or minus 0.4% relative to the reference standard. Qualitative and quantitative assay results verified the chemical integrity of the ethylene oxide-treated artesunate. These results establish the time zero data point for future ethylene oxide-treated artesunate stability studies.
Six thousand dry-filled vials of formulated artesunic acid for clinical use have been packaged. One thousand of the vials have been reserved for long-term stability testing under various conditions, including elevated temperatures and humidities, to test the integrity and durability of the packaging system. As packaged for clinical use, 20 ml vials have been dry-filled with 110 mg of ethylene oxide sterilized artesunic acid, stoppered, and sealed. Stability studies at Knoll have shown at least two years stability for bulk artesunic acid stored under nitrogen @ 25° C.
Example 2
Preclinical Toxicology
Tests of the dry-filled artesunate formulation were used in the GLP 14-day dog toxicity study. A concentrated formulation of 50 mg AS/ml was developed and manufactured for a 14-day cGLP toxicity study in dogs. The dry-filled artesunic acid formulation used in the GLP 14-day dog toxicity study was confirmed to be of high purity by independent analysis. The artesunic acid content weights, calculated from determining the mg of artesunic acid/mL in reconstituted samples, met the requirements set forth in USP Article <905> and ranged between 501 to 519 mg/vial.
The potential toxicity of GMP artesunate of the invention was tested in beagle dogs. The artesunate was administered daily by rapid intravenous infusion (over 4 to 6 minutes) for 14 days. Four groups consisting of 4 dogs/sex/group were treated daily with doses of artesunate at 10, 20, 35, or 50 mg/kg/day at dose volumes of 1 mL/kg. One group of 4 dogs/sex received sterile 0.3 M phosphate buffer (control article) and served as the control group. The study was divided into two parts. After 14 doses, 2 dogs/sex/group were necropsied on study day (SD) 15. The remaining two dogs/sex/group were allowed a 2-week treatment-free recovery period and were necropsied on study day 29. Measurements included survival, clinical observations, body weights, electrocardiography, hematology, clinical chemistry, coagulation parameters, gross pathology, organ weights, and histopathology (Wu and Senate, 2004). Intravenous doses of artesunate up to and including 50 mg/kg/day did not result in test article-related effects on mortality, clinical observations, body weights, body weight gains, food consumption, electrocardiographic output, clinical chemistry and coagulation, gross pathology, organ weights, and histopathology. During the course of the study, erythema, diarrhea, emesis, mucoid feces, and soft feces were observed sporadically in both control and test article-treated groups, and were not considered to be test article-related. Intravenous administration of artesunate at doses of 20, 35, or 50 mg/kg/day for 14 days in beagle dogs resulted in lowered red blood cell parameters (RBC, HGB, HCT, and RETIC) measured on study day 15. The lower reticulocyte counts suggested that there was not a regenerative response to the lower RBCs. The lowered red blood cell parameters found on study day 15 were not present on study day 29.
Based on the results of this study, artesunate, when administered intravenously for 14 days at doses up to and including 50 mg/kg/day, did not result in any other test article-related adverse effects except on the measure hematology. At doses of 20 mg/kg/day and above, intravenous administration of artesunate for 14 days resulted in a transient test article-related effect on red blood cell parameters, including RBC, HGB, HCT, and RETIC.
Having now fully described the invention, it will be apparent to one of ordinary skill in the art that many changes and modifications can be made thereto without departing from the spirit or scope of the invention as set forth herein. | A method for the manufacture of a sterile intravenous or intramuscular formulation of artesunic acid and the formulation are the subject of this invention. First the artesunic acid powder is sterilized with ethylene oxide and placed into a sterile container. The contained sterilized powder is then dissolved in sterile sodium phosphate buffered solution to produce an injectable intravenous or intramuscular formulation. The sodium phosphate dissolves and dilutes the artesunic acid powder without caking or frothing resulting in an improved drug product. The invention also relates to the formulation and a method of treating a patient with either uncomplicated or severe and complicated malaria. | 0 |
FIELD OF THE INVENTION AND RELATED ART
The present invention relates to a liquid crystal composition used in a liquid crystal display device, a liquid crystal-optical shutter, etc., more particularly to a novel liquid crystal composition with improved responsiveness to an electric field and a liquid crystal device using the liquid crystal composition.
Hitherto, liquid crystal devices have been used as an electro-optical device in various fields. Most liquid crystal devices which have been put into practice use TN (twisted nematic) type liquid crystals, as shown in "Voltage-Dependent Optical Activity of a Twisted Nematic Liquid Crystal" by M. Schadt and W. Helfrich "Applied Physics Letters" Vol. 18, No. 4 (Feb. 15, 1971) pp. 127-128.
These devices are based on the dielectric alignment effect of a liquid crystal and utilize an effect that the average molecular axis direction is directed to a specific direction in response to an applied electric field because of the dielectric anisotropy of liquid crystal molecules. It is said that the limit of response speed is on the order of milli-seconds, which is too slow for many uses. On the other hand, a simple matrix system of driving is most promising for application to a large-area flat display in view of cost, productivity, etc., in combination. In the simple matrix system, an electrode arrangement wherein scanning electrodes and signal electrodes are arranged in a matrix, and for driving, a multiplex driving scheme is adopted wherein an address signal is sequentially, periodically and selectively applied to the scanning electrodes and prescribed data signals are selectively applied in parallel to the signal electrodes in synchronism with the address signal.
When the above-mentioned TN-type liquid crystal is used in a device of such a driving system, a certain electric field is applied to regions where a scanning electrode is selected and signal electrodes are not selected or regions where a scanning electrode is not selected and a signal electrode is selected (which regions are so called "half-selected points"). If the difference between a voltage applied to the selected points and a voltage applied to the half-selected points is sufficiently large, and a voltage threshold level required for allowing liquid crystal molecules to be aligned or oriented perpendicular to an electric field is set to a value therebetween, display devices normally operate. However, in fact, as the number (N) of scanning lines increases, a time (duty ratio) during which an effective electric field is applied to one selected point when a whole image area (corresponding to one frame) is scanned decreases with a ratio of 1/N. Accordingly, the larger the number of scanning lines are, the smaller is the voltage difference of an effective value applied to a selected point and non-selected points when scanning is repeatedly effected. As a result, this leads to unavoidable drawbacks of lowering of image contrast or occurrence of interference or crosstalk. These phenomena are regarded as essentially unavoidable problems appearing when a liquid crystal having no bistability (i.e. liquid crystal molecules are horizontally oriented with respect to the electrode surface as stable state and is vertically oriented with respect to the electrode surface only when an electric field is effectively applied) is driven (i.e. repeatedly scanned) by making use of a time storage effect. To overcome these drawbacks, the voltage averaging method, the two-frequency driving method, the multiple matrix method, etc. has been already proposed. However, any method is not sufficient to overcome the above-mentioned drawbacks. As a result, it is the present state that the development of large image area or high packaging density in respect to display elements is delayed because it is difficult to sufficiently increase the number of scanning lines.
To overcome drawbacks with such prior art liquid crystal devices, the use of liquid crystal devices having bistability has been proposed by Clark and Lagerwall (e.g. Japanese Laid-Open Patent Appln. No. 56-107216, U.S. Pat. No. 4,367,924, etc.). In this instance, as the liquid crystals having bistability, ferroelectric liquid crystals having chiral smectic C-phase (SmC*) or H-phase (SmH*) are generally used. These liquid crystals have bistable states of first and second stable states with respect to an electric field applied thereto. Accordingly, as different from optical modulation devices in which the above-mentioned TN-type liquid crystals are used, the bistable liquid crystal molecules are oriented to first and second optically stable states with respect to one and the other electric field vectors, respectively. Further, this type of liquid crystal has a property (bistability) of assuming either one of the two stable states in response to an applied electric and retaining the resultant state in the absence of an electric field.
In addition to the above-described characteristic of showing bistability, such a ferroelectric liquid crystal (hereinafter sometimes abbreviated as "FLC") has an excellent property, i.e., a high-speed responsiveness. This is because the spontaneous polarization of the ferroelectric liquid crystal and an applied electric field directly interact with each other to induce transition of orientation state. The resultant response speed is faster than the response speed due to the interaction between dielectric anisotropy and an electric field by 3 to 4 digits.
Thus, a ferroelectric liquid crystal potentially has very excellent characteristics, and by making use of these properties, it is possible to provide essential improvements to many of the above-mentioned problems with the conventional TN-type devices. Particularly, the application to a high-speed optical shutter and a display of a high density and a large picture is expected. For this reason, there has been made extensive research with respect to liquid crystal materials showing ferroelectricity. However, ferroelectric liquid crystal materials developed heretofore cannot be said to satisfy sufficient characteristics required for a liquid crystal device including low-temperature operation characteristic, high-speed responsiveness, etc. Among a response time τ, the magnitude of spontaneous polarization Ps and viscosity η, the following relationship exists: τ=η/(Ps·E), where E is an applied voltage. Accordingly, a high response speed can be obtained by (a) increasing the spontaneous polarization Ps, (b) lowering the viscosity η, or (c) increasing the applied voltage E. However, the driving voltage has a certain upper limit in view of driving with IC, etc., and should desirably be as low as possible. Accordingly, it is actually necessary to lower the viscosity η or increase the spontaneous polarization Ps.
A ferroelectric chiral smectic liquid crystal having a large spontaneous polarization generally provides a large internal electric field in a cell given by the spontaneous polarization and is liable to pose many constraints on the device construction giving bistability. Further, an excessively large spontaneous polarization is liable to accompany an increase in viscosity, so that remarkable increase in response speed may not be attained as a result.
Further, if it is assumed that the operation temperature of an actual display device is 5-40° C., the response speed changes by a factor of about 20, so that it actually exceeds the range controllable by driving voltage and frequency.
As described hereinabove, commercialization of a ferroelectric liquid crystal device requires a ferroelectric chiral smectic liquid crystal composition having a low viscosity, a high-speed responsiveness and a small temperature-dependence of response speed.
In a representative FLC cell structure, a pair of substrates are disposed, each substrate of e.g. glass being provided with an electrode pattern of e.g. ITO, further thereon with a layer of e.g. SiO 2 (about 1000 Å) for preventing short circuit between the pair of substrates and further thereon with a film of e.g. polyimide (PI; such as SP-510, 710, . . . available from Toray K. K.) of about 400 Å in thickness, which is then treated for alignment control by rubbing with e.g. an acetate fiber-planted cloth. Such a pair of substrates are disposed opposite to each other so that their alignment control directions are symmetrical and the spacing between the substrates is held at 1-3 microns.
On the other hand, it is known that the ferroelectric liquid crystal molecules under such non-helical conditions are disposed in succession so that their directors (longer molecular axes) are gradually twisted between the substrates and do not shown a uniaxial orientation or alignment (i.e., in a splay alignment state). A problem in this case is a low transmittance through the liquid crystal layer.
Transmitted light intensity I through a liquid crystal is given by the following equation with respect to the incident light intensity I 0 under cross nicols when the uniaxial alignment of the molecules is assumed:
I=I.sub.0 sin.sup.2 (4θa) sin.sup.2 (πΔnd/λ) (1),
wherein Δn denotes the refractive index anisotropy of the FLC; d, the cell thickness; λ, the wavelength of the incident light; and θa, a half of the angle between two stable states (tilt angle).
When a conventional FLC cell is used, it has been experimentally known that θa is 5-8 degrees under a twisted alignment condition. The control of physical properties affecting the term Δndπ/λ cannot be easily performed, so that it is desired to increase θa to increase I. However, this has not been successfully accomplished by only a static alignment technique.
With respect to such a problem, it has been proposed to utilize a torque relating to a dielectric anisotropy Δε of an FLC (1983 SID report from AT & T; Japanese laid-Open Patent Applns. 245142/1986, 267722/1986, 246723/1986, 246724/1986, 249024/1986 and 249025/1986). More specifically, a liquid crystal molecule having a negative Δε tends to become parallel to the substrates under application of an electric field. By utilizing this property, if an effective value of AC electric field is applied even in a period other than switching, the above-mentioned twisted alignment is removed, so that θa is increased to provide an increased transmittance (AC stabilization effect).
SUMMARY OF THE INVENTION
An object of the present invention is to provide a chiral smectic liquid crystal composition having a large response speed and a decreased temperature-dependence of the response speed adapted for providing a practical ferroelectric liquid crystal device.
Another object of the present invention is to provide a liquid crystal composition which shows an AC stabilization effect providing remarkably improved display characteristics.
A further object of the present invention is to provide a liquid crystal device using such a liquid crystal composition and showing improved driving and display characteristics.
According to the present invention, there is provided a liquid crystal composition, comprising
at least one compound represented by the following formula (I): ##STR10## wherein R 1 and R 2 respectively denote an optically inactive linear or branched alkyl group having 1-18 carbon atoms capable of including one or non-neighboring two or more methylene groups which can be replaced with at least one species of ##STR11## wherein Z denotes --O-- of --S-- and R 3 denotes hydrogen or an alkyl group having 1-5 carbon atoms; A denotes --A 1 -- or --A 2 --A 3 -- wherein A 1 denotes ##STR12## and A 2 and A 3 respectively denote ##STR13## or --A 1 --; and
at least one compound represented by the following formula (II): ##STR14## wherein R 4 denotes a linear or branched alkyl group having 1-18 carbon atoms capable of having a substituent; X 1 denotes a single bond, --O--, ##STR15## X 2 denotes a single bond, --O-- or ##STR16## Z 1 denotes a single bond or ##STR17## A 4 denotes ##STR18## and l is 1-12.
The present invention further provides a liquid crystal device comprising a pair of substrates and such a ferroelectric liquid crystal composition as described above disposed between the electrode plates.
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
FIG. 1 is a schematic sectional view of a liquid crystal display device using a ferroelectric liquid crystal; and
FIGS. 2 and 3 are schematic perspective views of a device cell embodiment for illustrating the operation principle of a ferroelectric liquid crystal device.
DETAILED DESCRIPTION OF THE INVENTION
Preferred examples of the compounds represented by the above-mentioned general formula (I) may include those represented by the following formulas (I-a) to (I-h). ##STR19##
In the formulas (I-a) to (I-h), R 1 and R 2 are respectively the same as in the general formula (I). Preferred examples of R 1 and R 2 may include the following combinations (I-i) to (I-vi): ##STR20##
In the above combinations (I-i) to (I-vi), m is 1-18, n is 1-17, p is 0-7, q is 0 or 1, r is 0-7 and s is 0-7; R 5 , R 6 and R 7 respectively denote a linear or branched alkyl group; and X 3 denotes a single bond, --O--, ##STR21##
Further, preferred examples of the compounds represented by the above-mentioned general formula (II) may include those represented by the following formulas (II-a) to (II-c). ##STR22##
In the formulas (II-a) to (II-c), R 4 , X 1 , X 2 and l are respectively the same as in the general formula (II).
Specific examples of the compounds represented by the above-mentioned general formula (I) may include those shown by the following structural formulas. ##STR23##
The compounds represented by the general formula (I) may be synthesized through the following reaction schemes A and B. ##STR24##
In the above reaction schemes A and B, R 1 , R 2 and A are the same as defined in the general formula (I).
Further, in a case where a methylene group in R 2 adjacent to A is replaced with --O--, ##STR25## etc., it is possible to form a group of R 2 --A-- through the following steps (a) to (c):
(a) The above-mentioned replacing group combined with A is modified with addition of a protective group into a non-reactive or less reactive group such as ##STR26##
(b) Ring closure is effected to form a thiadiazole ring.
(c) The protective group is eliminated and then the R 2 --A-- structure is formed.
Some representative examples of synthesis of the compound represented by the general formula (I) are shown hereinbelow.
SYNTHESIS EXAMPLE 1
2-(4'-heptyloxy-4"-biphenyl)-5-octyl-1,3,4-thiadiazole (Example Compound No. I-54) was synthesized through the following steps i)-iii). ##STR27##
Step i) Production of nonanohydrazide
83.5 of hydrazine hydrate was added to a solution of 120 g of ethyl nananoate in 130 ml of ethanol, followed by heat-refluxing for 6 hours. After the reaction, the reaction mixture was cooled to precipitate a crystal. The crystal was recovered by filtration and recrystallized from 300 ml of ethanol to obtain 85 of nonanohydrazide.
Step ii) Production of N-nonanoyl-N'-4-(4'-heptyloxyphenyl)benzoylhydrazine
1.6 g of nonanohydrazide was dissolved in 18 ml of pyridine and heated to 40° C. To the above solution, a solution of 3.3 g of 4-heptyloxy-4'-biphenylcarbonyl chloride in 10 ml of dry benzene was added dropwise, followed by overnight stirring at room temperature. After the reaction, the reaction solution was diluted with ethyl acetate, followed by washing with water to precipitate an insoluble. The insoluble was recovered by filtration, followed by recrystallization from N,N-dimethylformamide to obtain 4.1 g of N-nonanoyl-N'-4-(4'-heptyloxyphenyl)benzoylhydrazine.
Step iii) Production of 2-(4'-heptyloxy-4"-biphenyl)-5-octyl-1,3,4-thiadiazole
To a solution of 3.1 g (6.65×10 -3 mol) of N-nonanoyl-N'-4-(4'-heptyloxyphenyl)benzoylhydrazine in 20 ml of pyridine, 1.99 g (8.98×10 -3 mol of diphosphorus pentasulfide was added at room temperature in 15 minutes, followed by heating to 100° C. for 6 hours of reaction. After the reaction, the reaction mixture was poured into a mixture solution of 10 ml ethanol and 200 ml of water, followed by three times of extraction with 100 ml of chloroform, washing with water, drying with anhydrous magnesium sulfate and distilling-off of the solvent to obtain 3.9 g of a crude crystal. The crude crystal was purified by column chromatography (mobile phase: chloroform/ethyl acetate=20/1, stationary phase: silica gel) to obtain objective 2-(4'-heptyloxy-4"-biphenyl)-5-octyl-1,3,4-thiadiazole.
Phase transition temperature (°C.) ##STR28## Herein, the respective symbols denote the following phases, Iso.: isotropic phase, Sm1-Sm3: smectic phases (unidentified), and Cryst.: crystal phase.
SYNTHESIS EXAMPLE 2
2-hexyl-5-[4'-(4"-pentylcyclohexyl)phenyl]-1,3,4-thiadiazole (Example Compound No. I-70) was synthesized through the following steps i)-iii). ##STR29##
Step i) Production of heptanohydrazide
12.2 g of hydrazine hydrate was added to a solution of 15 g of ethyl heptanoate in 20 ml of ethanol, followed by heat-refluxing for 4.5 hours. After the reaction, the reaction mixture was cooled to precipitate a crystal. The crystal was recovered by filtration and recrystallized from 20 ml of ethanol to obtain 7 g of heptanohydrazide.
Step ii) Production of N-heptanoyl-N'-4-(4'-pentylcyclohexyl)benzoylhydrazine
2.0 g of heptanohydrazide was dissolved in 27 ml of pyridine and heated to 40° C. To the above solution, a solution of 4.4 g of 4-(4'-pentylcyclohexyl)benzoyl chloride in 12 ml of dry benzene was added dropwise, followed by overnight stirring at room temperature. After the reaction, the reaction solution was diluted with ethyl acetate, followed by washing with water to precipitate an insoluble. The insoluble was recovered by filtration, followed by recrystallization from N,N-dimethylformamide to obtain 4.0 g of N-heptanoyl-N'-4-(4'-pentylcyclohexyl)benzohydrazine.
Step iii) Production of 2-hexyl-5-[4'-(4"-pentylcyclohexyl)phenyl]-1,3,4-thiadiazole
To a solution of 3.75 g of N-heptanoyl-N'-4-(4'-pentylcyclohexyl)benzoylhydrazine in 30 ml of pyridine, 2.81 g of diphosphorus pentasulfide was added at room temperature in 15 minutes, followed by heating to 100° C. for 6 hours of reaction. After the reaction, the reaction mixture was poured into a mixture solution of 10 ml ethanol and 200 ml of water to precipitate a crystal. The crystal was recovered by filtration and dried to obtain 4.6 g of a crude product. The crude product was dissolved in toluene and then the insoluble was removed from the solution by filtration. The resultant solution was purified by column chromatography (mobile phase: toluene, stationary phase: silica gel) to obtain 0.31 g of an objective product.
Phase transition temperature (°C.) ##STR30##
SYNTHESIS EXAMPLE 3
2-octyl-5-[4'-(4"-pentylphenyl)cyclohexyl]-1,3,4-thiadiazole (Example Compound No. I-76) was synthesized through the following steps i) and ii). ##STR31##
Step i) Production of N-octanoyl-N'-4-(4'-pentylphenyl)cyclohexanecarbonylhydrazine
2.4 g of nonanohydrazide prepared in the same manner as in Synthesis Example 1 was dissolved in 27 ml of pyridine and heated to 40° C. To the above solution, a solution of 4.4 g of 4-(4'-pentylphenyl)cyclohexanecarbonyl chloride in 12 ml of dry benzene was added dropwise, followed by overnight stirring at room temperature. After the reaction, the reaction solution was diluted with ethyl acetate, followed by washing with water to precipitate an insoluble. The insoluble was recovered by filtration, followed by recrystallization from N,N-dimethylformamide to obtain 4.6 g of N-nonanoyl-N'-4-(4'-pentylphenyl)cyclohexanecarbonylhydrazine.
Step ii) Production of 2-octyl-5-[4'-(4"-pentylphenyl)cyclohexyl]-1,3,4-thiadiazole
To a solution of 4.55 g of N-nonanoyl-N'-4-(4'-pentylphenyl)cyclohexanecarbonylhydrazine in 35 ml of pyridine, 3.19 g of diphosphorus pentasulfide was added at room temperature in 15 minutes, followed by heating to 100° C. for 6 hours of reaction. After the reaction, the reaction mixture was poured into a mixture solution of 15 ml ethanol and 300 ml of water, followed by extraction with chloroform, washing with water, drying with anhydrous magnesium sulfate and distilling-off of the solvent to obtain 5.3 g of a half-solid product. The product was purified by column chromatography (mobile phase: hexane/ethyl acetate=10/2, stationary phase: silica gel), followed by recrystallization from ethanol to obtain 0.2 g of 2-octyl-5-[4'-(4"-pentylphenyl)cyclohexyl]-1,3,4-thiadiazole.
Phase transition temperature (°C.) ##STR32##
SYNTHESIS EXAMPLE 4
2-hexyl-5-[4'-(5-heptyl-2-pyrimidinyl)-phenyl]-1,3,4-thiadiazole (Example Compound No. I-85) was synthesized through the following steps i) and ii). ##STR33##
Step i) Production of N-heptanoyl-N'-4-(5'-heptyl-2'-pyrimidinyl)benzoylhydrazine
2.0 g of heptanohydrazide prepared in the same manner as in Synthesis Example 2 was dissolved in 27 ml of pyridine and heated to 40° C. To the above solution, a solution of 4.7 g of 4-(5'-heptyl-2'-pyrimidinyl)benzoyl chloride in 20 ml of dry benzene was added dropwise, followed by overnight stirring at room temperature. After the reaction, the reaction solution was diluted with ethyl acetate, followed by washing with water to precipitate an insoluble. The insoluble was recovered by filtration, followed by recrystallization from N,N-dimethylformamide to obtain 3.1 g of N-heptanoyl-N'-4-(5'-heptyl-2'-pyrimidinyl)benzoylhydrazine.
Step ii) Production of 2-hexyl-5-[4'-(5-heptyl-2-pyrimidinyl)phenyl]-1,3,4-thiadiazole
To a solution of 2.6 g of N-heptanoyl-N'-4-(5'-heptyl-2'-pyrimidinyl)benzoylhydrazine in 20 ml of pyridine, 1.84 g of diphosphorus pentasulfide was added at room temperature in 15 minutes, followed by heating to 100° C. for 6 hours of reaction. After the reaction, the reaction mixture was poured into a mixture solution of 10 ml ethanol and 200 ml of water, followed by three times of extraction with 100 ml of chloroform, washing with water, drying with anhydrous magnesium sulfate and distilling-off of the solvent to obtain 2.5 g of a crude crystal. The crude crystal was purified by column chromatography (mobile phase: toluene/ethyl acetate=2/1, stationary phase: silica gel) to obtain objective 2-hexyl-5-[4'-(5-heptyl-2-pyrimidinyl)-phenyl]-1,3,4-thiadiazole.
Phase transition temperature (°C.) ##STR34##
Specific examples of the compounds represented by the above-mentioned general formula (II) may include those shown by the following structural formulas. ##STR35##
The compounds represented by the general formula (II) may be synthesized through the following reaction schemes A, B and C. ##STR36##
Some representative examples of synthesis of the compound represented by the general formula (II) are shown hereinbelow.
SYNTHESIS EXAMPLE 5
Synthesis of Compound Example II-17
1.00 g (4.16 mM) of p-2-fluorooctyloxyphenol was dissolved in a mixture of 10 ml of pyridine and 5 ml of toluene, and a solution of 1.30 g (6.0 mM) of trans-4-n-pentylcyclohexanecarbonyl chloride in 5 ml of toluene was added dropwise thereto in 20-40 min. below 5° C. After the addition, the mixture was stirred overnight at room temperature to obtain a white precipitate.
After the reaction, the reaction product was extracted with benzene, and the resultant benzene layer was washed with distilled water, followed by drying with magnesium sulfate and distilling-off of the benzene, purification by silica gel column chromatography and recrystallization from ethanol/methanol to obtain 1.20 g (2.85 mM) of trans-4-n-pentylcyclohexanecarboxylic acid-p-2-fluorooctyloxyphenyl-ester.
(Yield: 68.6%)
NMR data (ppm) 0.83-2.83 ppm (34H, m); 4.00-4.50 ppm (2H, q); 7.11 ppm (4H, s)
IR data (cm -1 ) 3456, 2928, 2852, 1742, 1508, 1470, 1248, 1200, 1166, 1132, 854.
Phase transition temperature (°C.) ##STR37## Herein, the respective symbols denote the following phases, Iso.: isotropic phase, Ch.: cholesteric phase, SmA: smectic A phase, SmC*: chiral smectic C phase, S 3 -S 6 : phases of higher order than SmC*, and Cryst.: crystal phase.
SYNTHESIS EXAMPLE 6
Synthesis of Compound Example II-34
In a vessel sufficiently replaced with nitrogen, 0.40 g (3.0 mmol) of (-)-2-fluoroheptanol and 1.00 g (13 mmol) of dry pyridine were placed and stirred for 30 min. under cooling on an ice bath. Into the solution, 0.69 g (3.6 mmol) of p-toluenesulfonyl chloride was added, and the mixture was stirred for 5 hours. After the reaction, 10 ml of 1N-HCl was added, and the resultant mixture was subjected to two times of extraction with 10 ml of methylene chloride. The extract liquid was washed once with 10 ml of distilled water and dried with an appropriate amount of anhydrous sodium sulfate, followed by distilling-off of the solvent to obtain 0.59 g (2.0 mmol) of (+)-2-fluoroheptyl p-toluenesulfonate.
The yield was 66%, and the product showed the following optical rotation and IR data.
Optical rotation: [α] D 26 .4 +2.59 degrees (c=1, CHCl 3 ); [α] 435 23 .6 +9.58 degrees (c=1, CHCl 3 )
IR (cm -1 ): 2900, 2850, 1600, 1450, 1350, 1170, 1090 980, 810, 660, 550
0.43 g (1.5 mmol) of the thus obtained (+)-2-fluoroheptyl p-toluenesulfonate and 0.28 g (1.0 mmol) of 5-octyl-2-(4-hydroxyphenyl)pyrimidine were mixed with 0.2 ml of 1-butanol, followed by sufficient stirring. To the solution was quickly added a previously obtained alkaline solution of 0.048 g (1.2 mmol) of sodium hydroxide in 1.0 ml of 1-butanol, followed by 5.5 hours of heat-refluxing. After the reaction, 10 ml of distilled water was added, and the mixture was extracted respectively once with 10 ml of benzene and 5 ml of benzene, followed by drying with an appropriate amount of anhydrous sodium sulfate, distilling-off of the solvent and purification by silica gel column chromatography (chloroform) to obtain 0.17 g (0.43 mmol) of objective (+)-5-octyl-2-[4-(2-fluoroheptyloxy)phenyl]pyrimidine.
The yield was 43%, and the product showed the following optical rotation and IR data.
Optical rotation: [α] D 25 .6 +0.44 degree (c=1, CHCl 3 ); [α] 435 22 .4 +4.19 degrees (c=1, CHCl 3 )
IR (cm -1 ) 2900, 2850, 1600, 1580, 1420, 1250 1160, 800, 720, 650, 550.
The liquid crystal composition according to the present invention may be obtained by mixing at least one species of the compound represented by the formula (I), at least one species of the compound represented by the formula (II) and at least one species of another mesomorphic compound in appropriate proportions. The liquid crystal composition according to the present invention may preferably be formulated as a ferroelectric liquid crystal composition, particularly a ferroelectric chiral smectic liquid crystal composition.
Specific examples of another mesomorphic compound as described above may include those denoted by the following structural formulas. ##STR38##
In formulating the liquid crystal composition according to the present invention, it is desirable to mix 1-300 wt. parts each, preferably 2-100 wt. parts each, of a compound represented by the formula (I) and a compound represented by the formula (II) with 100 wt. parts of another mesomorphic compound as mentioned above which can be composed of two or more species.
Further, when two or more species of either one or both of the compounds represented by the formulas (I) and (II) are used, the two or more species of the compound of the formula (I) or (II) may be used in a total amount of 1-500 wt. parts, preferably 2-100 wt. parts, per 100 wt. parts of another mesomorphic compound as described above which can be composed of two or more species.
The ferroelectric liquid crystal device according to the present invention may preferably be prepared by heating the liquid crystal composition prepared as described above into an isotropic liquid under vacuum, filling a blank cell comprising a pair of oppositely spaced electrode plates with the composition, gradually cooling the cell to form a liquid crystal layer and restoring the normal pressure.
FIG. 1 is a schematic sectional view of an embodiment of the ferroelectric liquid crystal device prepared as described above for explanation of the structure thereof.
Referring to FIG. 1, the ferroelectric liquid crystal device includes a ferroelectric liquid crystal layer 1 disposed between a pair of glass substrates 2 each having thereon a transparent electrode 3 and an insulating alignment control layer 4. Lead wires 6 are connected to the electrodes so as to apply a driving voltage to the liquid crystal layer 1 from a power supply 7. Outside the substrates 2, a pair of polarizers 8 are disposed so as to modulate incident light I 0 from a light source 9 in cooperation with the liquid crystal 1 to provide modulated light I.
Each of two glass substrates 2 is coated with a transparent electrode 3 comprising a film of In 2 O 3 , SnO 2 or ITO (indium-tin-oxide) to form an electrode plate. Further thereon, an insulating alignment control layer 4 is formed by rubbing a film of a polymer such as polyimide with gauze or acetate fiber-planted cloth so as to align the liquid crystal molecules in the rubbing direction. Further, it is also possible to compose the alignment control layer of two layers, e.g., by first forming an insulating layer of an inorganic material, such as silicon nitride, silicon nitride containing hydrogen, silicon carbide, silicon carbide containing hydrogen, silicon oxide, boron nitride, boron nitride containing hydrogen, cerium oxide, aluminum oxide, zirconium oxide, titanium oxide, or magnesium fluoride, and forming thereon an alignment control layer of an organic insulating material, such as polyvinyl alcohol, polyimide, polyamide-imide, polyester-imide, polyparaxylylene, polyester, polycarbonate, polyvinyl acetal, polyvinyl chloride, polyvinyl acetate, polyamide, polystyrene, cellulose resin, melamine resin, urea resin, acrylic resin, or photoresist resin. Alternatively, it is also possible to use a single layer of inorganic insulating alignment control layer or organic insulating alignment control layer. An inorganic insulating alignment control layer may be formed by vapor deposition, while an organic insulating alignment control layer may be formed by applying a solution of an organic insulating material or a precursor thereof in a concentration of 0.1 to 20 wt. %, preferably 0.2-10 wt. %, by spinner coating, dip coating, screen printing, spray coating or roller coating, followed by curing or hardening under prescribed hardening condition (e.g., by heating). The insulating alignment control layer may have a thickness of ordinarily 50 Å-1 micron, preferably 100-3000 Å, further preferably 100-1000 Å. The two glass substrates 2 with transparent electrodes 3 (which may be inclusively referred to herein as "electrode plates") and further with insulating alignment control layers 4 thereof are held to have a prescribed (but arbitrary) gap with a spacer 5. For example, such a cell structure with a prescribed gap may be formed by sandwiching spacers of silica beads or alumina beads having a prescribed diameter with two glass plates, and then sealing the periphery thereof with, e.g., an epoxy adhesive. Alternatively, a polymer film or glass fiber may also be used as a spacer. Between the two glass plates, a ferroelectric liquid crystal is sealed up to provide a ferroelectric liquid crystal layer 1 in a thickness of generally 0.5 to 20 microns, preferably 1 to 5 microns.
The transparent electrodes 3 are connected to the external power supply 7 through the lead wires 6. Further, outside the glass substrates 2, polarizers 8 are applied. The device shown in FIG. 1 is of a transmission type and is provided with a light source 9.
FIG. 2 is a schematic illustration of a ferroelectric liquid crystal cell (device) for explaining operation thereof. Reference numerals 21a and 21b denote substrates (glass plates) on which a transparent electrode of, e.g., In 2 O 3 , SnO 2 , ITO (indium-tin-oxide), etc., is disposed, respectively. A liquid crystal of an SmC*-phase (chiral smectic C phase) or SmH*-phase (chiral smectic H phase) in which liquid crystal molecular layers 22 are aligned perpendicular to surfaces of the glass plates is hermetically disposed therebetween. Full lines 23 show liquid crystal molecules. Each liquid crystal molecule 23 has a dipole moment (P.sub.⊥) 24 in a direction perpendicular to the axis thereof. The liquid crystal molecules 23 continuously form a helical structure in the direction of extension of the substrates. When a voltage higher than a certain threshold level is applied between electrodes formed on the substrates 21a and 21b, a helical structure of the liquid crystal molecule 23 is unwound or released to change the alignment direction of respective liquid crystal molecules 23 so that the dipole moments (P.sub.⊥) 24 are all directed in the direction of the electric field. The liquid crystal molecules 23 have an elongated shape and show refractive anisotropy between the long axis and the short axis thereof. Accordingly, it is easily understood that when, for instance, polarizers arranged in a cross nicol relationship, i.e., with their polarizing directions crossing each other, are disposed on the upper and the lower surfaces of the glass plates, the liquid crystal cell thus arranged functions as a liquid crystal optical modulation device of which optical characteristics vary depending upon the polarity of an applied voltage.
Further, when the liquid crystal cell is made sufficiently thin (e.g., less than about 10 microns), the helical structure of the liquid crystal molecules is unwound to provide a non-helical structure even in the absence of an electric field, whereby the dipole moment assumes either of the two states, i.e., Pa in an upper direction 34a or Pb in a lower direction 34b as shown in FIG. 3, thus providing a bistable condition. When an electric field Ea or Eb higher than a certain threshold level and different from each other in polarity as shown in FIG. 3 is applied to a cell having the above-mentioned characteristics by using voltage application means 31a and 31b, the dipole moment is directed either in the upper direction 34a or in the lower direction 34b depending on the vector of the electric field Ea or Eb. In correspondence with this, the liquid crystal molecules are oriented in either of a first stable state 33a and a second stable state 33b.
When the above-mentioned ferroelectric liquid crystal is used as an optical modulation element, it is possible to obtain two advantages as described above. First is that the response speed is quite fast. Second is that the orientation of the liquid crystal molecules shows bistability. The second advantage will be further explained, e.g., with reference to FIG. 3. When the electric field Ea is applied to the liquid crystal molecules, they are oriented in the first stable state 33a. This state is stably retained even if the electric field is removed. On the other hand, when the electric field Eb of which direction is opposite to that of the electric field Ea is applied thereto, the liquid crystal molecules are oriented to the second stable state 33b, whereby the directions of molecules are changed. This state is similarly stably retained even if the electric field is removed. Further, as long as the magnitude of the electric field Ea or Eb being applied is not above a certain threshold value, the liquid crystal molecules are placed in the respective orientation states.
When such a ferroelectric liquid crystal device comprising a ferroelectric liquid crystal composition as described above between a pair of electrode plates is constituted as a simple matrix display device, the device may be driven by a driving method as disclosed in Japanese Laid-Open Patent Applications (KOKAI) Nos. 193426/1984, 193427/1984, 156046/1985, 156047/1985, etc.
Hereinbelow, the present invention will be explained more specifically with reference to examples. It is however to be understood that the present invention is not restricted to these examples.
EXAMPLE 1
A liquid crystal composition 1-A was prepared by mixing the following compounds in respectively indicated proportions.
__________________________________________________________________________Ex.CompoundNo. Structural formula Wt. parts__________________________________________________________________________ ##STR39## 1565 ##STR40## 566 ##STR41## 10195 ##STR42## 5201 ##STR43## 8197 ##STR44## 5203 ##STR45## 129 ##STR46## 911 ##STR47## 654 ##STR48## 582 ##STR49## 1585 ##STR50## 5__________________________________________________________________________
A liquid crystal composition 1-B was prepared by mixing the following example compounds in the proportions indicated below with the above-prepared composition 1-A.
__________________________________________________________________________Ex. Comp. No. Structural formula Wt. parts__________________________________________________________________________I-13 ##STR51## 2I-49 ##STR52## 4I-88 ##STR53## 3II-20 ##STR54## 2II-40 ##STR55## 3II-102 ##STR56## 2 Composition 1-A 84__________________________________________________________________________
The above-prepared liquid crystal composition 1-B was used to prepare a liquid crystal device in combination with a blank cell prepared in the following manner.
Two 1.1 mm-thick glass plates were provided and respectively coated with an ITO film to form an electrode for voltage application, which was further coated with an insulating layer of vapor-deposited SiO 2 . The insulating layer was further coated with a 1.0%-solution of polyimide resin precursor (SP-710, available from Toray K.K.) in dimethylacetoamide by a spinner coater rotating at 2500 rpm for 15 seconds. Thereafter, the coating film was subjected to heat curing at 300° C. for 60 min. to obtain about 200 Å-thick film. The coating film was rubbed with acetate fiber-planted cloth. The thus treated two glass plates were washed with isopropyl alcohol. After silica beads with an average particle size of 1.5 microns were dispersed on one of the glass plates, the two glass plates were applied to each other with a bonding sealing agent (Lixon Bond, available from Chisso K.K.) so that their rubbed directions were parallel to each other and heated at 100° C. for 60 min. to form a blank cell. The cell gap was found to be about 1.5 microns as measured by a Berek compensator.
Then, the above-prepared liquid crystal composition 1-B was heated into an isotropic liquid, and injected into the above prepared cell under vacuum and, after sealing, was gradually cooled at a rate of 20° C./hour to 25° C. to prepare a ferroelectric liquid crystal device.
The ferroelectric liquid crystal device was subjected to measurement of an optical response time (time from voltage application until the transmittance change reaches 90% of the maximum) at specified temperatures under the application of a peak-to-peak voltage Vpp of 25 volts in combination with right-angle cross-nicol polarizers. The results are shown below.
______________________________________ 10° C. 25° C. 40° C.______________________________________Response time 786 μsec 259 μsec 106 μsec______________________________________
Further, a contrast of 12.5 was attained at 25° C. during the driving, and a clear switching function was observed. The bistability after termination of the voltage application was also good.
COMPARATIVE EXAMPLE 1
A liquid crystal composition 1-C was prepared by omitting Example compounds Nos. II-20, II-40 and II-102 from the liquid crystal composition 1-B prepared in Example 1, i.e., by adding only Example compounds Nos. I-13, I-49 and I-88 to the liquid crystal composition 1-A, and a liquid crystal composition 1-D was prepared by omitting Example compounds Nos. I-13, I-49 and I-88 from the composition 1-B, i.e., by adding only Example compounds Nos. II-20, II-40 and II-102 to the composition 1-A.
Ferroelectric liquid crystal devices 1-A, 1-C and 1-D were prepared by using the compositions 1-A, 1-C and 1-D, respectively, instead of the composition 17-B, and subjected to measurement of optical response time, otherwise in the same manner as in Example 1. The results are shown below.
Response Time
______________________________________Response time10° C. 25° C. 40° C.______________________________________1-A 1410 μsec 435 μsec 155 μsec1-C 1209 μsec 372 μsec 138 μsec1-D 910 μsec 292 μsec 120 μsec______________________________________
As apparent from the above Example 1 and Comparative Example 1, the ferroelectric liquid crystal device containing the liquid crystal composition 1-B according to the present invention provided improved response speed and operation characteristic at a lower temperature and also provided a descreased temperature dependence of response speed (ratio of response time (10° C./40° C.)).
EXAMPLE 2
A liquid crystal composition 2-B was prepared by mixing the following example compounds in the indicated proportions with the liquid crystal composition 1-A prepared in Example 1.
__________________________________________________________________________Ex. Comp.No. Structural formula wt. parts__________________________________________________________________________I-21 ##STR57## 3I-44 ##STR58## 3I-73 ##STR59## 2II-11 ##STR60## 2II-45 ##STR61## 4II-96 ##STR62## 2 Composition 1-A 84__________________________________________________________________________
A ferroelectric liquid crystal device was prepared in the same manner as in Example 1 except that the above liquid crystal composition 2-B was used, and the device was subjected to measurement of optical response time and observation of switching states. In the device, a monodomain with a good and uniform alignment characteristic was observed. The results of the measurement are shown below.
______________________________________ 10° C. 25° C. 40° C.______________________________________Response time 734 μsec 248 μsec 106 μsec______________________________________
Further, a contrast of 11.9 was attained at 25° C. during the driving, and a clear switching function was observed. The bistability after termination of the voltage application was also good.
COMPARATIVE EXAMPLE 2
A liquid crystal composition 2-C was prepared by omitting Example compounds Nos. II-11, II-45 and II-96 from the liquid crystal composition 2-B prepared in Example 2, i.e., by adding only Example compounds Nos. I-21, I-44 and I-73 to the liquid crystal composition 1-A, and a liquid crystal composition 2-D was prepared by omitting Example compounds Nos. I-21, I-44 and I-73 from the composition 2-B, i.e., by adding only Example compounds Nos. II-11, II-45 and II-96 to the composition 1-A.
Ferroelectric liquid crystal devices 1-A, 2-C and 2-D were prepared by using the compositions 1-A, 2-C and 2-D, respectively, instead of the composition 1-B, and subjected to measurement of optical response time, otherwise in the same manner as in Example 1. The results are shown below.
Response time
______________________________________Response time10° C. 25° C. 40° C.______________________________________1-A 1410 μsec 435 μsec 155 μsec2-C 1214 μsec 371 μsec 136 μsec2-D 847 μsec 283 μsec 119 μsec______________________________________
As apparent from the above Example 2 and Comparative Example 2, the ferroelectric liquid crystal device containing the liquid crystal composition 2-B according to the present invention provided improved response speed and operation characteristic at a lower temperature and also provided a descreased temperature dependence of response speed.
EXAMPLE 3
A liquid crystal composition 3-B was prepared by mixing the following example compounds in the indicated proportions with the liquid crystal composition 1-A prepared in Example 1.
__________________________________________________________________________Ex. Comp.No. Structural formula wt. parts__________________________________________________________________________I-29 ##STR63## 4I-38 ##STR64## 2I-44 ##STR65## 3II-3 ##STR66## 2II-75 ##STR67## 2II-93 ##STR68## 2 Composition 1-A 85__________________________________________________________________________
A ferroelectric liquid crystal device was prepared in the same manner as in Example 1 except that the above liquid crystal composition 3-B was used, and the device was subjected to measurement of optical response time and observation of switching states. In the device, a monodomain with a good and uniform alignment characteristic was observed. The results of the measurement are shown below.
______________________________________ 10° C. 25° C. 40° C.______________________________________Response time 858 μsec 278 μsec 109 μsec______________________________________
Further, a contrast of 11.2 was attained at 25° C. during the driving, and a clear switching function was observed. The bistability after termination of the voltage application was also good.
COMPARATIVE EXAMPLE 3
A liquid crystal composition 3-C was prepared by omitting Example compounds Nos. II-3, II-75 and II-93 from the liquid crystal composition 3-B prepared in Example 3, i.e., by adding only Example compounds Nos. I-29, I-38 and I-44 to the liquid crystal composition 1-A, and a liquid crystal composition 3-D was prepared by omitting Example compounds Nos. I-29, I-38 and I-44 from the composition 3-B, i.e., by adding only Example compounds Nos. II-3, II-75 and II-93 to the composition 1-A.
Ferroelectric liquid crystal devices 1-A, 3-C and 3-D were prepared by using the compositions 1-A, 3-C and 3-D, respectively, instead of the composition 1-B, and subjected to measurement of optical response time, otherwise in the same manner as in Example 1. The results are shown below.
Response time (μsec)
______________________________________Response time (μsec)10° C. 25° C. 40° C.______________________________________1-A 1410 435 1553-C 1206 372 1353-D 992 315 124______________________________________
As apparent from the above Example 3 and Comparative Example 3, the ferroelectric liquid crystal device containing the liquid crystal composition 3-B according to the present invention provided improved response speed and operation characteristic at a lower temperature and also provided a decreased temperature dependence of response speed.
EXAMPLE 4
A liquid crystal composition 4-B was prepared by mixing the following example compounds in the indicated proportions with the liquid crystal composition 1-A prepared in Example 1.
__________________________________________________________________________Ex. Comp.No. Structural formula wt. parts__________________________________________________________________________I-28 ##STR69## 4I-58 ##STR70## 2II-17 ##STR71## 3II-39 ##STR72## 3II-50 ##STR73## 2 Composition 1-A 86__________________________________________________________________________
A ferroelectric liquid crystal device was prepared in the same manner as in Example 1 except that the above liquid crystal composition 4-B was used, and the device was subjected to measurement of optical response time and observation of switching states. In the device, a monodomain with a good and uniform alignment characteristic was observed. The results of the measurement are shown below.
______________________________________ 10° C. 25° C. 40° C.______________________________________Response time 809 μsec 272 μsec 112 μsec______________________________________
Further, a contrast of 12.4 was attained at 25° C. during the driving, and a clear switching function was observed. The bistability after termination of the voltage application was also good.
COMPARATIVE EXAMPLE 4
A liquid crystal composition 4-C was prepared by omitting Example compounds Nos. II-17, II-39 and II-50 from the liquid crystal composition 4-B prepared in Example 4, i.e., by adding only Example compounds Nos. I-28 and I-58 to the liquid crystal composition 1-A, and a liquid crystal composition 4-D was prepared by omitting Example compounds Nos. I-28 and I-58 from the composition 4-B, i.e., by adding only Example compounds Nos. II-17, II-39 and II-50 to the composition 1-A.
Ferroelectric liquid crystal devices 1-A, 4-C and 4-D were prepared by using the compositions 1-A, 4-C and 4-D, respectively, instead of the composition 1-B, and subjected to measurement of optical response time, otherwise in the same manner as in Example 1. The results are shown below.
Response time (μsec)
______________________________________Response time (μsec)10° C. 25° C. 40° C.______________________________________1-A 1410 435 1554-C 1229 379 1374-D 918 303 124______________________________________
As apparent from the above Example 4 and Comparative Example 4, the ferroelectric liquid crystal device containing the liquid crystal composition 4-B according to the present invention provided improved response speed and operation characteristic at a lower temperature and also provided a descreased temperature dependence of response speed.
EXAMPLE 5
A liquid crystal composition 5-A was prepared by mixing the following compounds in respectively indicated proportions.
__________________________________________________________________________Ex. Comp. No. Structural formula wt. parts__________________________________________________________________________195 ##STR74## 6201 ##STR75## 8197 ##STR76## 9203 ##STR77## 1218 ##STR78## 319 ##STR79## 3 9 ##STR80## 311 ##STR81## 366 ##STR82## 1554 ##STR83## 1563 ##STR84## 882 ##STR85## 985 ##STR86## 6__________________________________________________________________________
A liquid crystal composition 5-B was prepared by mixing the following example compounds in the indicated proportions with the liquid crystal composition 5-A.
__________________________________________________________________________Ex. Comp. No. Structural formula wt. parts__________________________________________________________________________I-7 ##STR87## 2I-32 ##STR88## 4I-51 ##STR89## 4II-18 ##STR90## 4II-33 ##STR91## 2II-98 ##STR92## 3 Composition 5-A 81__________________________________________________________________________
A ferroelectric liquid crystal device was prepared in the same manner as in Example 1 except that the above liquid crystal composition 5-B was used, and the device was subjected to measurement of optical response time and observation of switching states. In the device, a monodomain with a good and uniform alignment characteristic was observed. The results of the measurement are shown below.
______________________________________ 10° C. 25° C. 40° C.______________________________________Response time 745 μsec 261 μsec 102 μsec______________________________________
Further, a contrast of 10.6 was attained at 25° C. during the driving, and a clear switching function was observed. The bistability after termination of the voltage application was also good.
COMPARATIVE EXAMPLE 5
A liquid crystal composition 5-C was prepared by omitting Example compounds Nos. II-18, II-33 and II-98 from the liquid crystal composition 5-B prepared in Example 5, i.e., by adding only Example compounds Nos. I-7, I-32 and I-51 to the liquid crystal composition 5-A, and a liquid crystal composition 5-D was prepared by omitting Example compounds Nos. I-7, I-32 and I-51 from the composition 5-B, i.e., by adding only Example compounds Nos. II-18, II-33 and II-98 to the composition 5-A.
Ferroelectric liquid crystal devices 5-A, 5-C and 5-D were prepared by using the compositions 5-A, 5-C and 5-D, respectively, instead of the composition 1-B, and subjected to measurement of optical response time, otherwise in the same manner as in Example 1. The results are shown below.
Response time (μsec)
______________________________________Response time (μsec)10° C. 25° C. 40° C.______________________________________5-A 1155 362 1335-C 968 322 1185-D 873 278 110______________________________________
As apparent from the above Example 5 and Comparative Example 5, the ferroelectric liquid crystal device containing the liquid crystal composition 5-B according to the present invention provided improved response speed and operation characteristic at a lower temperature and also provided a descreased temperature dependence of response speed.
EXAMPLE 6
A liquid crystal composition 6-B was prepared by mixing the following example compounds in the indicated proportions with the liquid crystal composition 5-A prepared in Example 5.
__________________________________________________________________________Ex. Comp. No. Structural formula wt. parts__________________________________________________________________________I-41 ##STR93## 2I-61 ##STR94## 4I-70 ##STR95## 2II-59 ##STR96## 4II-107 ##STR97## 2II-116 ##STR98## 2 Composition 5-A 84__________________________________________________________________________
A ferroelectric liquid crystal device was prepared in the same manner as in Example 1 except that the above liquid crystal composition 6-B was used, and the device was subjected to measurement of optical response time and observation of switching states. In the device, a monodomain with a good and uniform alignment characteristic was observed. The results of the measurement are shown below.
______________________________________ 10° C. 25° C. 40° C.______________________________________Response time 782 μsec 272 μsec 102 μsec______________________________________
Further, a contrast of 10.1 was attained at 25° C. during the driving, and a clear switching function was observed. The bistability after termination of the voltage application was also good.
COMPARATIVE EXAMPLE 6
A liquid crystal composition 6-C was prepared by omitting Example compounds Nos. II-59, II-107 and II-116 from the liquid crystal composition 6-B prepared in Example 6, i.e., by adding only Example compounds Nos. I-41, I-61 and I-70 to the liquid crystal composition 5-A, and a liquid crystal composition 6-D was prepared by omitting Example compounds Nos. I-41, I-61 and I-70 from the composition 6-B, i.e., by adding only Example compounds Nos. II-59, II-107 and II-116 to the composition 5-A.
Ferroelectric liquid crystal devices 5-A, 6-C and 6-D were prepared by using the compositions 5-A, 6-C and 6-D, respectively, instead of the composition 1-B, and subjected to measurement of optical response time, otherwise in the same manner as in Example 1. The results are shown below.
Response time (μsec)
______________________________________Response time (μsec)10° C. 25° C. 40° C.______________________________________5-A 1155 362 1336-C 995 335 1226-D 899 289 110______________________________________
As apparent from the above Example 6 and Comparative Example 6, the ferroelectric liquid crystal device containing the liquid crystal composition 6-B according to the present invention provided improved response speed and operation characteristic at a lower temperature and also provided a descreased temperature dependence of response speed.
EXAMPLE 7
A liquid crystal composition 7-B was prepared by mixing the following example compounds in the indicated proportions with the liquid crystal composition 5-A prepared in Example 5.
__________________________________________________________________________Ex. Comp. No. Structural formula wt. parts__________________________________________________________________________I-24 ##STR99## 3I-49 ##STR100## 3I-76 ##STR101## 2II-13 ##STR102## 2II-69 ##STR103## 2II-104 ##STR104## 4 Composition 5-A 84__________________________________________________________________________
A ferroelectric liquid crystal device was prepared in the same manner as in Example 1 except that the above liquid crystal composition 7-B was used, and the device was subjected to measurement of optical response time and observation of switching states. In the device, a monodomain with a good and uniform alignment characteristic was observed. The results of the measurement are shown below.
______________________________________ 10° C. 25° C. 40° C.______________________________________Response time 781 μsec 269 μsec 101 μsec______________________________________
Further, a contrast of 11.2 was attained at 25° C. during the driving, and a clear switching function was observed. The bistability after termination of the voltage application was also good.
COMPARATIVE EXAMPLE 7
A liquid crystal composition 7-C was prepared by omitting Example compounds Nos. II-13, II-69 and II-104 from the liquid crystal composition.7-B prepared in Example 7, i.e., by adding only Example compounds Nos. I-24, I-49 and I-76 to the liquid crystal composition 5-A, and a liquid crystal composition 7-D was prepared by omitting Example compounds Nos. I-24, I-49 and I-76 from the composition 7-B, i.e., by adding only Example compounds Nos. II-13, II-69 and II-104 to the composition 5-A.
Ferroelectric liquid crystal devices 5-A, 7-C and 7-D were prepared by using the compositions 5-A, 7-C and 7-D, respectively, instead of the composition 1-B, and subjected to measurement of optical response time, otherwise in the same manner as in Example 1. The results are shown below.
Response time (μsec)
______________________________________Response time (μsec)10° C. 25° C. 40° C.______________________________________5-A 1155 362 1337-C 991 331 1197-D 895 283 109______________________________________
As apparent from the above Example 7 and Comparative Example 7, the ferroelectric liquid crystal device containing the liquid crystal composition 7-B according to the present invention provided improved response speed and operation characteristic at a lower temperature and also provided a descreased temperature dependence of response speed.
EXAMPLE 8
A liquid crystal composition 8-B was prepared by mixing the following example compounds in the indicated proportions with the liquid crystal composition 5-A prepared in Example 5.
__________________________________________________________________________Ex. Comp. No. Structural formula wt. parts__________________________________________________________________________I-53 ##STR105## 4I-81 ##STR106## 2I-85 ##STR107## 3II-2 ##STR108## 4II-95 ##STR109## 2 Composition 5-A 85__________________________________________________________________________
A ferroelectric liquid crystal device was prepared in the same manner as in Example 1 except that the above liquid crystal composition 8-B was used, and the device was subjected to measurement of optical response time and observation of switching states. In the device, a monodomain with a good and uniform alignment characteristic was observed. The results of the measurement are shown below.
______________________________________ 10° C. 25° C. 40° C.______________________________________Response time 778 μsec 267 μsec 98 μsec______________________________________
Further, a contrast of 10.5 was attained at 25° C. during the driving, and a clear switching function was observed. The bistability after termination of the voltage application was also good.
COMPARATIVE EXAMPLE 8
A liquid crystal composition 8-C was prepared by omitting Example compounds Nos. II-2 and II-95 from the liquid crystal composition 8-B prepared in Example 8, i.e., by adding only Example compounds Nos. I-53, I-81 and I-85 to the liquid crystal composition 5-A, and a liquid crystal composition 8-D was prepared by omitting Example compounds Nos. I-53, I-81 and I-85 from the composition 8-B, i.e., by adding only Example compounds Nos. II-2 and II-95 to the composition 5-A.
Ferroelectric liquid crystal devices 5-A, 8-C and 8-D were prepared by using the compositions 5-A, 8-C and 8-D, respectively, instead of the composition 1-B, and subjected to measurement of optical response time, otherwise in the same manner as in Example 1. The results are shown below.
______________________________________Response time (μsec)10° C. 25° C. 40° C.______________________________________5-A 1155 362 1338-C 988 328 1208-D 970 306 118______________________________________
As apparent from the above Example 8 and Comparative Example 8, the ferroelectric liquid crystal device containing the liquid crystal composition 8-b according to the present invention provided improved response speed and operation characteristic at a lower temperature and also provided a descreased temperature dependence of response speed.
EXAMPLE 9
A liquid crystal composition 9-B was prepared by mixing the following compounds in respectively indicated proportions.
__________________________________________________________________________Ex. Comp. No. Structural formula wt. parts__________________________________________________________________________18 ##STR110## 1819 ##STR111## 18 9 ##STR112## 811 ##STR113## 887 ##STR114## 12210 ##STR115## 1290 ##STR116## 6157 ##STR117## 6160 ##STR118## 6177 ##STR119## 4189 ##STR120## 2__________________________________________________________________________
A liquid crystal composition 9-B was prepared by mixing the following example compounds in the indicated proportions with the liquid crystal composition 9-A.
__________________________________________________________________________Ex. Comp. No. Structural formula wt. parts__________________________________________________________________________I-21 ##STR121## 3I-53 ##STR122## 4I-89 ##STR123## 2II-12 ##STR124## 2II-33 ##STR125## 2II-100 ##STR126## 2 Composition 9-A 85__________________________________________________________________________
A ferroelectric liquid crystal device was prepared in the same manner as in Example 1 except that the above liquid crystal composition 9-B was used, and the device was subjected to measurement of optical response time and observation of switching states. In the device, a monodomain with a good and uniform alignment characteristic was observed. The results of the measurement are shown below.
______________________________________ 10° C. 25° C. 40° C.______________________________________Response time 629 μsec 187 μsec 68 μsec______________________________________
Further, a contrast of 11.4 was attained at 25° C. during the driving, and a clear switching function was observed. The bistability after termination of the voltage application was also good.
COMPARATIVE EXAMPLE 9
A liquid crystal composition 9-C was prepared by omitting Example compounds Nos. II-12, II-33 and II-100 from the liquid crystal composition 9-B prepared in Example 9, i.e., by adding only Example compounds Nos. I-21, I-53 and I-89 to the liquid crystal composition 9-A, and a liquid crystal composition 9-D was prepared by omitting Example compounds Nos. I-21, I-53 and I-89 from the composition 9-B, i.e., by adding only Example compounds Nos. II-12, II-33 and II-100 to the composition 9-A.
Ferroelectric liquid crystal devices 9-A, 9-C and 9-D were prepared by using the compositions 9-A, 9-C and 9-D, respectively, instead of the composition 1-B, and subjected to measurement of optical response time, otherwise in the same manner as in Example 1. The results are shown below.
______________________________________Response time (μsec)10° C. 25° C. 40° C.______________________________________9-A 1180 326 1009-C 1037 292 929-D 697 208 75______________________________________
As apparent from the above Example 9 and Comparative Example 9, the ferroelectric liquid crystal device containing the liquid crystal composition 9-B according to the present invention provided improved response speed and operation characteristic at a lower temperature and also provided a descreased temperature dependence of response speed.
EXAMPLE 10
A liquid crystal composition 10-B was prepared by mixing the following example compounds in the indicated proportions with the liquid crystal composition 9-A prepared in Example 9.
__________________________________________________________________________Ex. Comp.No. Structural formula wt. parts__________________________________________________________________________I-6 ##STR127## 2I-59 ##STR128## 4I-92 ##STR129## 4II-5 ##STR130## 3II-86 ##STR131## 3 Composition 9-A 84__________________________________________________________________________
A ferroelectric liquid crystal device was prepared in the same manner as in Example 1 except that the above liquid crystal composition 10-B was used, and the device was subjected to measurement of optical response time and observation of switching states. In the device, a monodomain with a good and uniform alignment characteristic was observed. The results of the measurement are shown below.
______________________________________ 10° C. 25° C. 40° C.______________________________________Response time 641 μsec 122 μsec 70 μsec______________________________________
Further, a contrast of 11.2 was attained at 25° C. during the driving, and a clear switching function was observed. The bistability after termination of the voltage application was also good.
COMPARATIVE EXAMPLE 10
A liquid crystal composition 10-C was prepared by omitting Example compounds Nos. II-5 and II-86 from the liquid crystal composition 10-B prepared in Example 10, i.e., by adding only Example compounds Nos. I-6, I-59 and I-92 to the liquid crystal composition 9-A, and a liquid crystal composition 10-D was prepared by omitting Example compounds Nos. I-6, I-59 and I-92 from the composition 10-B, i.e., by adding only Example compounds Nos. II-5 and II-86 to the composition 9-A.
Ferroelectric liquid crystal devices 9-A, 10-C and 10-D were prepared by using the compositions 9-A, 10-C and 10-D, respectively, instead of the composition 1-B, and subjected to measurement of optical response time, otherwise in the same manner as in Example 1. The results are shown below.
______________________________________Response time (μsec)10° C. 25° C. 40° C.______________________________________ 9-A 1180 326 10010-C 1022 289 9110-D 722 215 77______________________________________
As apparent from the above Example 10 and Comparative Example 10, the ferroelectric liquid crystal device containing the liquid crystal composition 10-B according to the present invention provided improved response speed and operation characteristic at a lower temperature and also provided a descreased temperature dependence of response speed.
EXAMPLE 11
A liquid crystal composition 11-B was prepared by mixing the following example compounds in the indicated proportions with the liquid crystal composition 9-A prepared in Example 9.
__________________________________________________________________________Ex. Comp.No. Structural formula wt. parts__________________________________________________________________________I-33 ##STR132## 3I-41 ##STR133## 2I-72 ##STR134## 2II-32 ##STR135## 2II-53 ##STR136## 2 II-112 ##STR137## 2 Composition 9-A 87__________________________________________________________________________
A ferroelectric liquid crystal device was prepared in the same manner as in Example 1 except that the above liquid crystal composition 11-B was used, and the device was subjected to measurement of optical response time and observation of switching states. In the device, a monodomain with a good and uniform alignment characteristic was observed. The results of the measurement are shown below.
______________________________________ 10° C. 25° C. 40° C.______________________________________Response time 604 μsec 185 μsec 68 μsec______________________________________
Further, a contrast of 11.7 was attained at 25° C. during the driving, and a clear switching function was observed. The bistability after termination of the voltage application was also good.
COMPARATIVE EXAMPLE 11
A liquid crystal composition 11-C was prepared by omitting Example compounds Nos. II-32, II-53 and II-112 from the liquid crystal composition 11-B prepared in Example 11, i.e., by adding only Example compounds Nos. I-33, I-41 and I-72 to the liquid crystal composition 9-A and a liquid composition composition 11-D was prepared by omitting Example compounds Nos. I-33, I-41 and I-72 from the composition 11-B, i.e., by adding only Example compounds Nos. II-32, II-53 and II-112 to the composition 9-A.
Ferroelectric liquid crystal devices 9-A, 11-C and 11-D were prepared by using the compositions 9-A, 11-C and 11-D, respectively, instead of the composition 1-B, and subjected to measurement of optical response time, otherwise in the same manner as in Example 1. The results are shown below.
______________________________________Response time (μsec)10° C. 25° C. 40° C.______________________________________ 9-A 1180 326 10011-C 1048 296 9211-D 666 202 74______________________________________
As apparent from the above Example 11 and Comparative Example 11, the ferroelectric liquid crystal device containing the liquid crystal composition 11-B according to the present invention provided improved response speed and operation characteristic at a lower temperature and also provided a descreased temperature dependence of response speed.
EXAMPLES 12-15
Liquid crystal compositions 12-B to 15-B were prepared by replacing the example compounds and the liquid crystal compositions used in Examples 1 and 5 with example compounds and liquid crystal compositions shown in the following Table 1. Ferroelectric liquid crystal devices were prepared by respectively using these compositions instead of the composition 1-B, and subjected to measurement of optical response time and observation of switching states. In the devices, a monodomain with a good and uniform alignment characteristic was observed. The results of the measurement are shown in the following Table 1.
TABLE 1__________________________________________________________________________ Example Compound No. or liquidEx. No. crystal composition No. Response time (μsec)(Comp. No.) (weight parts) 10° C. 25° C. 40° C.__________________________________________________________________________12 I-4 I-34 I-47 II-17 II-30 II-112 1-A 647 222 95(12-B) 2 2 4 2 4 4 8213 I-27 I-52 I-101 II-4 II-76 II-85 A-1 784 260 105(13-B) 3 3 2 4 2 2 8414 I-56 I-104 II-14 II-37 II-90 5-A 729 254 96(14-B) 4 2 3 3 2 8615 I-10 I-54 I-65 II-45 II-73 II-91 5-A 717 250 95(15-B) 2 4 3 3 2 2 84__________________________________________________________________________
As is apparent from the results shown in the above Table 1, the ferroelectric liquid crystal devices containing the liquid crystal compositions 12-B to 15-B provided improved response speed and operation characteristic at a lower temperature and also provided a decreased temperature dependence of the response speed.
EXAMPLE 16
A blank cell was prepared in the same manner as in Example 1 except for omitting the SiO 2 layer to form an alignment control layer composed of the polyimide resin layer alone on each electrode plate. Four ferroelectric liquid crystal devices were prepared by filling such a blank cell with liquid crystal compositions 1-B, 1-A, 1-C and 1-D, respectively, prepared in Example 1 and Comparative Example 1. These liquid crystal devices were subjected to measurement of optical response time in the same manner as in Example 1. The results are shown below.
______________________________________Response time (μsec)10° C. 25° C. 40° C.______________________________________1-B 708 237 981-A 1271 392 1411-C 1093 336 1251-D 822 264 110______________________________________
As is apparent from the above Example 16, also in the case of a different device structure, the device containing the ferroelectric liquid crystal composition 1-B according to the present invention provided improved operation characteristic at a lower temperature and also a decreased temperature dependence of response speed.
EXAMPLE 17
Two liquid crystal devices were prepared by using the liquid crystal compositions 1-B and 1-A used in Example 1 and Comparative Example 1, respectively, otherwise in the same manner as in Example 1.
The tilt angles of the above devices were measured under right-angle cross nicols at 25° C. and microscopic observation to provide 7.6 degrees for the liquid crystal composition 1-A and 8.1 degrees for the liquid crystal composition 1-B. Then, the devices were subjected to application of a ±8 V rectangular waveform at a frequency of 60 KHz, and the tilt angles were measured under the voltage application and microscopic observation to provide 8.7 degrees for the liquid crystal composition 1-A and 12.4 degrees for the liquid crystal composition 1-B. Under these conditions, the contrast ratios were measured to be 10:1 for the liquid crystal composition 1-A and 26:1 for the liquid crystal composition 1-B.
The above results showed the liquid crystal composition 1-B according to the present invention provided a remarkably improved display characteristic when used in a driving method utilizing AC application (or AC stabilization).
EXAMPLES 18-27
The liquid crystal devices were prepared by using the liquid crystal compositions 2-B to 11-B used in Example 2 to 11, respectively, and the liquid crystal compositions 1-A, 5-A and 9-A used in Comparative Examples 1, 5 and 9, respectively, otherwise in the same manner as in Example 1. The tilt angles of these devices were measured in the same manner as in Example 17. The results are shown below.
Tilt angle (degree, at 25° C.)
______________________________________ Tilt angle (degree, at 25° C.) Initial Under AC appln. (no electric (60 KHz, ±8 V,Comp. field) rectangular)______________________________________Ex. 18 1-A 7.6 8.7 2-B 8.1 11.9Ex. 19 3-B 7.9 12.2Ex. 20 4-B 8.2 12.5Ex. 21 5-A 7.3 8.2 5-B 7.9 12.3Ex. 22 6-B 7.6 11.4Ex. 23 7-B 7.8 11.7Ex. 24 8-B 8.0 12.2Ex. 25 9-A 7.1 7.9 9-B 7.6 11.5Ex. 26 10-B 7.8 11.9Ex. 27 11-B 7.5 11.6______________________________________
The above results showed the liquid crystal compositions 2-B to 11-B according to the present invention provided a remarkably improved display characteristic when used in a driving method utilizing AC application (or AC stabilization).
As described hereinabove, the ferroelectric liquid crystal composition according to the present invention provides a liquid crystal device which shows a good switching characteristic, an improved operation characteristic and a decreased temperature dependence of response speed. Further, the liquid crystal composition according to the present invention provides a liquid crystal device which shows a remarkably improved display characteristic when used in a driving method utilizing AC stabilization. | A liquid crystal composition, comprising: at least one compound represented by the following formula (I): ##STR1## wherein R 1 and R 2 respectively denote an optically inactive linear or branched alkyl group having 1-18 carbon atoms capable of including one or non-neighboring two or more methylene groups which can be replaced with at least one species of ##STR2## wherein Z denotes --O-- or --S-- and R 3 denotes hydrogen or an alkyl group having 1-5 carbon atoms; A denotes --A 1 -- or --A 2 --A 3 -- wherein A 1 denotes ##STR3## and A 2 and A 3 respectively denote ##STR4## or --A 1 --; and at least one compound represented by the following formula (II): ##STR5## wherein R 4 denotes a linear or branched alkyl group having 1-18 carbon atoms capable of having a substituent; X 1 denotes a single bond, --O--, ##STR6## X 2 denotes a single bond, --O-- or ##STR7## Z 1 denotes a single bond or ##STR8## A 4 denotes ##STR9## and l is 1-12. | 2 |
FIELD OF THE INVENTION
[0001] The present invention relates to physical fitness training. In particular, it relates to an apparatus and methods for physical fitness training.
BACKGROUND OF THE INVENTION
[0002] It is known to provide physical fitness training apparatus for exercise and body building. A wide variety of apparatus are known, including free weights and exercise machinery.
[0003] It is also known to provide, as a component of such prior art machinery, apparatus for exercising and developing the muscles of the chest known as the pectoralis major muscles (“pecs”) which extend from the centre of the chest outwardly to each shoulder, as shown in FIG. 1 .
[0004] A common form of pec building apparatus is also depicted in FIG. 1 . This equipment design requires the user to take a seated position between two elevated weight-bearing members. The user draws the weight-bearing members together along an arced path by contracting the pecs, and then releases the weight-bearing members by extending the pecs.
[0005] It would be desirable to have a system for developing the pecs which did not require a large, stationary piece of body-building equipment, but rather was lightweight, compact, portable and versatile to permit exercise of the pectoralis major muscle group in a more convenient manner. The fitness apparatus of the present invention achieves these objectives.
SUMMARY OF THE INVENTION
[0006] There is provided an exercise apparatus comprising anchor means reversibly connectable to a fixed location, resistance means connectable to the anchor means, arm support means connected to the resistance means, and fastening means for securing the arm support means to a user.
[0007] The anchor means may be a clip for attachment of the anchor means to an anchor point. The resistance means may be elastomeric cords, each attachable at a first end to the anchor means, and at a second end to the arm support means. The arm support means may be planar arm supports, each planar arm support attachable to a corresponding elastomeric cord. The fastening means may be one or more adjustable straps attachable to each planar support.
[0008] The invention may be used to perform a pectoral fly exercise in a standing position, and an abdominal crunch exercise with resistance in a supine position, as well as other exercises.
[0009] The arm support may be manufactured of one or more ethyl vinyl acetate foams, or it may be manufactured of a foam comprised of a polyethylene/ethyl vinyl acetate mixture.
[0010] Each arm support may further comprises opposing lateral walls along a portion of its length for providing lateral arm support to a user, and gripping means for allowing a user to clasp the arm support with a hand. The gripping means may be an opening in each arm support for insertion therethrough of the user's fingers, or a handle.
[0011] In another aspect, the invention provides a portable exercise apparatus comprising one or more planar arm supports for supporting one or both of a user's forearms; strapping means for securing each arm support to the user's forearms; one or more elastomeric cords attachable between each planar arm support and one or more anchor points; and anchor means for securing each elastomeric cord to the anchor points.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] A detailed description of the preferred embodiments is provided below by way of example only and with reference to the following drawings, in which:
[0013] FIG. 1 depicts use of a prior art apparatus for developing the pectoralis major muscles;
[0014] FIGS. 2A-D depict the apparatus of the present invention;
[0015] FIG. 3 is a perspective view of one embodiment of the present invention depicting a contoured arm support;
[0016] FIG. 4 is a perspective view of one embodiment of the adjustable strapping of the present invention;
[0017] FIG. 5 is a perspective view of one embodiment of the present invention depicting side enclosures on the arm supports;
[0018] FIG. 6 is a perspective view of one embodiment of the present invention depicting finger contours;
[0019] FIG. 7 depicts use of the apparatus of the present invention in a pecs exercise in an eccentric contraction starting horizontal plane position;
[0020] FIG. 8 depicts use of the apparatus of the present invention in a pecs exercise in a partial isokinetic contraction midway position;
[0021] FIG. 9 depicts use of the apparatus of the present invention in a pecs exercise in a full isokinetic contraction concentric position;
[0022] FIG. 10 depicts use of the apparatus of the present invention in an abdominals exercise in an extended position with legs bent;
[0023] FIG. 11 depicts use of the apparatus of the present invention in an abdominals exercise in an fully contracted position with legs bent;
[0024] FIG. 12 depicts use of the apparatus of the present invention in an abdominals exercise in a partially contracted position with legs raised;
[0025] FIG. 13 is a front perspective view of an alternate embodiment of an arm support of the invention; and
[0026] FIG. 14 is a rear perspective view of an alternate embodiment of an arm support of the invention.
[0027] In the drawings, one embodiment of the invention is illustrated by way of example. It is to be expressly understood that the description and drawings are only for the purpose of illustration and as an aid to understanding, and are not intended as a definition of the limits of the invention.
DETAILED DESCRIPTION OF THE INVENTION
[0028] The present invention comprises a convenient piece of fitness equipment that provides the opportunity to perform the fly movement at a different rate of resistance in an isokinetic contraction. The apparatus of the present invention stimulates and shapes the muscles of the chest, and also contributes to increasing the size of the pectoralis major and pectoralis minor muscles, without causing any harm to the user.
[0029] The apparatus of the present invention enables the user to perform the exercise movement in the horizontal plane. As a result, it is simple to use and comfortable on the user's body, thereby playing a vital and important role in strengthening and shaping the user's chest. In addition, by using the apparatus of the present invention with different types of body movement, the apparatus may be used to exercise and develop various muscles of the body, including the gluteus maximus, hip muscles, leg muscles, and abdominal muscles. Its easy to use design allows the user to effortlessly change its resistance to the user's personal preference to reach their individual goals. Whether used in home, at work, at the park, or even while traveling, its compact design allows for easy maneuverability.
[0030] As depicted in FIG. 2A , the apparatus of the present invention comprises one or more arm supports 2 each connectable to an elastic cord 4 . Each arm support is of a size and shape to provide a surface against which a user's forearm may be placed. Each arm support preferably is approximately 6 inches wide and approximately sixteen inches long, although other dimensions are also possible provided they dimensions are sufficient to provide support to a user's forearm. The shape of each arm support may also be varied to provide improved comfort and support, and to minimize the amount of material required, as depicted in FIG. 3 .
[0031] The arm supports are preferably manufactured of a lightweight material which is able to repel moisture from sweat, and which is very durable and easily cleaned with soap and water. Preferably, the material used for the arm supports is moldable to allow the arm supports to mold to the user's forearms for added support. A preferred material is non-toxic polyethylene/ethyl vinyl acetate (“PE/EVA”) foam, although other materials including certain plastics and fabric or foam covered wood or metal are also possible.
[0032] Each arm support is provided with strapping 6 to connect the arm support to the elastic cord stretchable from the arm supports. The strapping is preferably 1 inch to 1.5 inches wide, although other widths are also possible. The strapping also provides support for the forearms, assisting in maintaining the forearm position on the arm support. As shown in FIG. 4 , preferably, strap adjustment means 8 are provided on the strapping to enable the user to adjust the strapping to the dimensions of their arms. In one embodiment, the strapping may be significantly wider than 1.5 inches to provide lateral support to the forearms. In yet another embodiment shown in FIG. 5 , the arm supports may further include side supports to provide lateral supports to the forearms. The strapping may be a canvas-type material or other strong fabric with length adjustment means. Alternatively, the strapping may include Velcro fastening means to allow easy length adjustment.
[0033] In the preferred embodiment, the arm supports include one or more openings 10 near one end for placement therethrough of one or more fingers of the user's hands, as seen in FIG. 6 . The opening may further include contours for the placement and support of individual fingers. In an alternative embodiment, the arm support may instead include finger contours along one end instead of an opening. In yet another embodiment, the finger grip may be achieved with a channel for insertion of the fingers having a single opening near or at one end of the arm support.
[0034] The apparatus of the invention also comprises connection means 12 for connecting the strapping to an elastic cord stretchable between the arm supports. The elastic cord may also be directly attachable to the arm support. Preferably, the connection means is a triangular ring enabling ease of connection of the elastic cord thereto using clips 14 connected to the ends of the elastic cord. The triangular shape is preferred to limit movement of the elastic cord within the connection ring, but other shapes, including circular connection rings, are possible. Preferably, the connection means is manufactured of a strong metal such as steel, but other strong materials are also possible.
[0035] In a preferred embodiment, the invention further comprises anchor means for attachment of the elastic cord to a fixed point which provides the resistance to the user. The invention preferably comprises one elastic cord for use with each arm support, each elastic cord connectable to the anchor means. However, it is also possible to connect the arm supports to opposing ends of a single elastic cord and to connect the elastic cord to anchor means at a midpoint of the elastic cord, or to run the elastic cord around a fixed anchor point such as a tree or pole which provides the resistance required.
[0036] An alternate embodiment of the invention, having lateral arm support walls 16 , is shown in FIGS. 13 and 14 .
[0037] In operation, as depicted in FIGS. 7 to 9 , a pectoral exercise may be carried out by securely attaching the elastic cord or cords approximately 80″ from the ground. Other heights are also possible, depending on the height of the user. The strapping of the arm supports may then be attached through the connection means to the end of the elastic cord or cords. The user places the forearms into the arm supports and firmly grips the top of the arm supports with the fingers while in the eccentric contraction. The user stands with the back to the anchored cord at a desired distance selected to obtain the desired resistance. Placing one bent leg forward with the rear leg on its plantar flexion, the arms are extended out to the sides with elbows bent 90°, mimicking a prior art pec deck as depicted in FIG. 1 . Both arms are then drawn together along an arc until the arm supports are touching. Preferably, the user will tighten the chest muscles at the end of the concentric phase for maximum stimulation of the inner area of the chest muscles. Finally, the user draws the elbows back outwardly along the arc to return the arm supports to the side positions. The movement may then be repeated from the starting horizontal plane position for a desired number of repetitions.
[0038] Apart from development of the pectoral muscles, the apparatus of the present invention may be used to develop the muscles of the core. The core is the foundation of the human body. It is comprised of the muscles that span the hips, abdominals, back and shoulders. For every move from lifting a heavy box to swinging a bat, the core needs support. Developing a stronger core starts with rethinking the crunch. The effectiveness of hundreds of crunches on the ground is questionable. Rather, core exercises should engage the user's stabilizer muscles and challenge their balance.
[0039] Such core workouts may incorporate the apparatus of the present invention for an added challenge. As shown in FIGS. 10 to 12 , the present apparatus may easily be used to help strengthen and shape the mid section. FIG. 10 shows a user in a supine position with the elastic cord fixed from behind. Arms are raised above the head and slightly bent. Hands are still firmly grasping the top of the arm supports. Feet may be raised or flat on the floor. The user then contracts the abdominal muscles and bends forward slowly, raising the shoulders slightly off the ground until their body is at a 45 degree angle, as depicted in FIG. 11 . At an intermediate level, the user may lift the legs off the ground straight in front, as shown in FIG. 12 .
[0040] From the foregoing, it will be seen that this invention is one well adapted to attain all of the ends and objectives herein set forth, together with other advantages which are obvious and which are inherent to the apparatus. It will be understood that certain features and sub-combinations are of utility and may be employed with reference to other features and sub-combinations. This is contemplated by and is within the scope of the claims. As many possible embodiments may be made of the invention without departing from the scope of the claims. It is to be understood that all matter herein set forth or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense. It will be appreciated by those skilled in the art that other variations of the preferred embodiment may also be practiced without departing from the scope of the invention. | A portable exercise apparatus comprising one or more planar arm supports for supporting one or both of a user's forearms; strapping means for securing each arm support to the user's forearms; one or more elastomeric cords attachable between each planar arm support and one or more anchor points; and anchor means for securing each elastomeric cord to the anchor points. The apparatus may be used for pectoral exercises, core muscle exercises, and other exercises. | 0 |
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