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CROSS-REFERENCES TO RELATED APPLICATIONS
This application is the U.S. National Stage of International Application No. PCT/EP2010/002427, filed Apr. 21, 2010, which designated the United States and has been published as International Publication No. WO 2010/130329 and which claims the priority of German Patent Application, Serial No. 10 2009 021 093.8, filed May 13, 2009, pursuant to 35 U.S.C. 119(a)-(d).
BACKGROUND OF THE INVENTION
The invention relates to a wheel suspension of a motor vehicle.
In so-called active steering systems, especially for the rear axle of vehicles, the wheel camber or the wheel toe can be adjusted via an actuator so that handling of the motor vehicle can be influenced by controlling the actuator.
DE 10 2004 049 296 A1 discloses a generic wheel suspension for a motor vehicle. It includes a hub unit which rotatably supports the vehicle wheel, and an axle-side guide part, with rotary parts being disposed between the hub unit and the guide part. The rotary part facing the hub unit is a cylindrical adjusting ring having cylindrical inner and outer effective areas which interact with corresponding effective areas of the other rotary part and the hub unit. The rotation axes of both rotary parts are aligned at a slant in relation to one another. When the two rotary parts are rotated, the wheel toe or the wheel camber can be adjusted.
Both rotary parts can be rotated in any relation to one another by servo drives. The desired toe-in/camber adjustment can be established in dependence on the combination of the rotation angles. In the extreme case, the resultant diffraction angle may be in the order of several angle degrees. This means that the carrier part can be positioned at a slant at an angle of several angle degrees in relation to the guide part which is mounted with further suspension arms to the vehicle body.
SUMMARY OF THE INVENTION
The invention is based on the object to provide a wheel suspension which allows a reliable support of encountered radial forces and axial forces.
The object is solved by a wheel suspension for a motor vehicle, including a wheel-side carrier part rotatably supporting a vehicle wheel, and an axle-side wide part between which rotary parts are arranged and rotatable in relation to one another, with the guide part, the rotary parts and/or the carrier part interacting with facina first and second effective areas, wherein the facing effective areas between the guide part, the rotary part and/or the carrier part of the wheel suspension are not configured cylindrically but a first effective area may radially delimit a conical or spherical hollow profile in which the second facing effective area is able to at least substantially engage formfittingly.
The inventive idea may conceivably include different variants of the two facing effective areas: For example, both facing effective areas may have conical configuration, or a first one of the effective areas may be configured as spherical cup whereas the second effective area may have a corresponding spherical configuration to engage this spherical cup. As an alternative, the first effective area can be conical whereas the second effective area is a surface in the shape of a spherical disk to thereby establish a conical socket/spherical disk bearing.
According to a preferred embodiment, the two rotary parts placed between guide part and carrier part may form an actuator for adjusting a toe angle and/or camber angle. The facing effective areas can hereby be dimensioned between the two rotary parts in such a way as to slantingly position the rotation axis of the one rotary part in relation to the rotation axis of the other rotary part by an inclination angle.
In accordance with a variant, the facing effective areas can contact one another directly or through intervention of a friction-reducing coating so as to provide overall a cost-efficient and durable slide bearing between both effective areas.
As an alternative, the facing effective areas can be connected to one another via a roller bearing. This may be a tapered roller bearing when the effective areas have a conical configuration.
According to the invention, three bearing points are established between the four-part wheel carrier comprised of carrier part, the two rotary parts and the guide part. In order to reliably absorb axial and radial forces, it is of advantage to configure each of the bearing points with tapered roller bearings.
As described above, the second rotary part has an effective area which faces the first rotary part and an effective area which faces the guide part. For a particularly compact construction that is stable in axial direction, these two effective areas may be expanded in opposite directions to one another on the second rotary part.
As described above, the first rotary part has in contrast thereto an effective area which faces the carrier part and an effective area which faces the second rotary part, with both effective areas being expanded in a same direction in a conical or spherical manner.
In light of this background, the second rotary part may include in axial direction on both sides a conical or spherical hollow profile, respectively, for engagement of the first rotary part on one hand and also the guide part on the other hand. The carrier part can be further arranged with its effective area radially inwards of the first rotary part for better use of installation space.
The wheel-side carrier part and the axle-side guide part can be fixed by a restraining means. In particular, the restraining means can apply a biasing force to maintain the guide and carrier parts under tension in the axial direction. As a result of such a securement or bracing of the carrier and guide parts, the bearing points can be exposed to loads, in particular axial compressive forces and radial forces, while axial pulling forces may be absorbed by the restraining means itself.
With regard to assembly, it is beneficial to interconnect the four parts of the wheel carrier, comprised of carrier part, the rotary parts and the guide part, in an assembly direction roughly by a plug-in connection, without the need for an undercutting construction to axially fix the parts. The assembly may be implemented by simply plugging the parts together. For structural reasons, it is furthermore preferred when the restraining means connects the guide part and the carrier part with one another, wherein the restraining means can be arranged radially outside the rotary parts.
The restraining means may at the same time act as a coupling between the carrier part and the guide part. The coupling can again transmit as a torque bridge a torque, such as a braking torque, from the carrier part onto the guide part and thus to the vehicle body. The restraining means may hereby be configured preferably as cardan joint or metal bellows.
BRIEF DESCRIPTION OF THE DRAWING
The invention will now be described with reference to several exemplified embodiments.
It is shown in:
FIG. 1 a basic representation of the device for adjusting toe and camber angles of a wheel suspension for motor vehicles with a multi-part wheel carrier;
FIG. 2 a concrete implementation of the device according to FIG. 1 , having a carrier part which carries a wheel, a guide part which is articulated on wheel guide elements of the wheel suspension, and two pivotable rotary parts which can be adjusted by electric servomotors;
FIG. 3 the device according to FIG. 2 by way of an enlarged illustration of the arrangement and pivotal support of the rotary parts and the carrier and guide parts;
FIG. 4 a greatly simplified view of the device for illustration of the adjustment mechanism; and
FIGS. 5 a to 5 c various variants of the effective areas between the two rotary parts.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
For a theoretical explanation of the invention, FIG. 1 shows a rough basic representation of a wheel carrier 10 of a wheel suspension for motor vehicles, which carrier is subdivided for adjustment of the camber and/or toe of the vehicle wheel as follows:
The wheel carrier 10 has a carrier part 12 in which the wheel and the brake element (brake disk, brake drum) of a service brake of the motor vehicle is rotatably supported. It should be noted that any functional parts of the wheel suspension that have not been described can be of conventional structure.
The wheel carrier 10 further includes a guide part 14 which interacts with the wheel suspension or optionally may form part of the wheel suspension.
Two substantially rotation-symmetrical rotary parts 16 , 18 are provided as actuators between the carrier part 12 and the guide part 14 and are connected for rotation with the carrier part 12 and the guide part 14 , respectively, via respective rotation axes 20 , 22 . Both rotation axes 20 , 22 are oriented coaxially in the figures and extend in the wheel rotation axis.
Whereas the contact surfaces of the rotary parts 16 , 18 directly adjacent to the carrier part 12 and the guide part 14 are configured rotation-symmetrically, the rotary parts 16 , 18 bear upon one another via slanted surfaces 16 b , 18 b in such a way that the rotary part 16 pivots about a rotation axis 24 which is inclined upwards in FIG. 1 . The rotation axis 24 is thus oriented, as shown, perpendicular to the slanted surfaces 16 b , 18 b and inclined at a defined angle x in relation to the rotation axis 22 .
In FIG. 1 , the center axis 20 of the carrier part 12 is oriented in coaxial relation to the rotation axis 22 of the guide part 14 so that the vehicle wheel, held on the carrier part 12 , is set without camber and toe angles. FIG. 4 , which is being described further below, indicates in addition also the center axis 20 ′. The shown angular disposition of the center axis 20 ′ is established as the rotary parts 16 , 18 pivot about a rotation angle of 180°.
Provided on the carrier part 12 and the guide part 13 are electric servomotors 26 , 28 , respectively, which are connected in driving relationship with the rotary parts 16 , 18 in the basic representation via toothed belts 30 . The rotary parts 16 , 18 can be rotated by the servomotors 26 , 28 in same direction or in opposite direction in both rotational directions so that the carrier part 12 executes a pivoting motion or a wobbling motion in order to accordingly change the toe angle and/or the camber angle of the wheel.
FIGS. 2 and 3 show a longitudinal section of a concrete embodiment of the wheel carrier 10 along the rotation axis 22 of the wheel of the wheel suspension.
As described above, the wheel carrier 10 is comprised of the guide part 14 which is articulated to wheel guide elements such as suspension arms etc., the carrier part 12 which supports the wheel, and the rotation-symmetrical rotary parts 16 , 18 .
The guide part 14 has a support flange 34 which supports a radially inwardly arranged bearing ring 36 . According to FIG. 3 , the conical effective area 36 a of the bearing ring 36 faces the conical effective area 18 a of the radially outwardly arranged rotary part 18 . The bearing ring 36 forms via bearing rollers 38 with the radially outwardly arranged rotary part 18 a first tapered roller bearing which is defined by a rotation axis in coincidence with the rotation axis 22 .
The rotary part 18 has an outer circumference provided with a gear rim 18 c which interacts in driving relationship with an invisible drive gear of the electric servomotor 28 . The servomotor 28 is also mounted to the support flange 34 of the guide part 14 .
According to FIG. 3 , the carrier part 12 has a radially aligned flange portion 40 and an axially extending hub portion 42 . The hub portion 42 extends radially within the two rotary parts 16 , 18 up to a level with the bearing ring 36 of the support flange 34 .
Provided within the flange portion 40 is a wheel bearing 44 as pivot bearing for a wheel flange 46 which has a hub portion 48 which projects likewise axially to the hub portion 42 also roughly up to the bearing ring 36 .
The wheel or the wheel rim 32 and the brake disk 52 of a disk brake are fastened to the wheel flange 46 by wheel bolts 50 (shown also partially). The caliper of the disk brake is fastened to the flange portion 40 of the carrier part 12 in a manner which is not apparent.
Furthermore, the rotary part 16 is rotatably supported on the hub portion 42 via an inner bearing ring 54 and a tapered roller bearing 56 , with the rotation axis of the hub portion also coinciding with the wheel rotation axis 22 . The inner bearing ring 54 and the radially outer rotary part 16 have facing conical effective areas 54 a and 16 a between which the tapered roller bearing 56 is provided.
The rotary part 16 is further rotatably supported in the rotary part 18 via a third tapered roller bearing 58 with bearing rollers. The relevant conical effective areas 16 b , 18 b are hereby slantingly configured in relation to the rotation axis 22 so that a rotation causes adjustment of the camber angle and/or toe angle of the wheel from the neutral position in a range of about 5°.
According to FIG. 3 , the rotary part 16 engages into an axial groove 40 a of the flange portion 40 and supports an outer gear rim 16 c which is connected in driving relationship with the servomotor 26 via a hidden drive gear and through a recess in the flange portion 40 . The servomotor 26 is respectively fastened to the flange portion 40 of the carrier part 12 .
The wheel flange 46 is operated via a cardan shaft 60 , shown only in part by way of its bell-shaped joint housing 62 and the sleeve-shaped driving journal 64 for the sake of simplicity. The driving journal 64 is inserted via a spline 64 a into the hub portion 48 of the wheel flange 46 and tightened by a locking bolt 66 with a locking sleeve 68 against the wheel flange 46 . A distance sleeve 69 is supported between a ring shoulder of the bell-shaped joint housing 62 and the wheel bearing 44 and arranged in coaxial relationship to and in radial direction between the hub portions 42 , 48 of the carrier part 12 and the wheel flange 46 . The locking bolt 66 thus braces the assembly comprised of locking sleeve 68 , wheel flange 46 , wheel bearing 44 , distance sleeve 69 , and cardan shaft 60 .
According to FIGS. 2 and 3 , a cardan ring 72 is provided radially outside the rotary parts 16 , 18 as restraint against rotation between the guide part 14 and the carrier part 12 and is guided on the flange portion 40 of the carrier part 12 in circumferential direction in a formfitting manner via, for example, axial catches which project into the cardan ring 72 . The cardan ring permits only angular deflections but no relative rotation.
The device for adjustment of the wheel camber and/or toe, as described above, is sealed radially to the outside against environmental impacts such as moisture and dirt by a rubber-elastic bellows 74 (cf. FIG. 2 ). The bellows 74 is respectively fastened to ring-shaped projections 40 a , 34 a of the flange portion 40 of the carrier part 12 and the support flange 34 of the guide part 14 .
As an alternative, as shown in FIG. 4 , the bellows 74 may be configured as thin-walled metallic bellows which is sufficiently torsionally rigid to provide restraint against rotation but yet is sufficiently flexible as to lastingly accommodate the mentioned adjustment angles while sealing the radially inwardly arranged functional parts. The described cardan ring 72 can then be omitted.
A radial inner sealing of the rotary parts 16 , 18 and their roller bearings etc. is provided between the bearing ring 36 on the support plate 34 of the guide part 14 and the hub portion 42 of the carrier part 12 in the region of the bell-shaped joint housing 62 of the cardan shaft 60 . It should be noted in this context that the carrier part 12 executes a wobbling motion with a pivot center in the middle of the cardan joint at M ( FIG. 4 ) so that sufficient clearance should be provided at the annular gap between the bell-shaped joint housing 62 and the bearing ring 36 .
A sleeve-shaped sealing ring 76 is supported on the hub portion 42 for axial displacement to ensure reliable sealing and has on its end face a spherical portion 76 a which interacts with a concavely shaped recess 36 b in the bearing ring 36 .
FIG. 4 shows in a greatly simplified way the adjustment mechanism of the wheel suspension according to the invention. Therefore, the servomotors 26 , 28 within the metal bellows 74 are operatively connected with the rotary parts 16 , 18 which are indicated by the arrows. As already described with reference to FIG. 3 , the rotary part 18 has two effective areas 18 a and 18 b . The effective areas 18 a , 18 b are expanded conically in mutually opposite directions.
The effective areas 18 b and 16 b of both rotary parts 16 , 18 , which areas are relevant for camber and toe adjustment are inclined upwards at a slant to the rotation axis 22 by a cone angle (y+x) and (y−x), respectively. The conical effective areas 54 a , 16 a between the bearing ring 54 and the rotary part 16 are hereby nested within one another in axial direction.
FIGS. 5 a to 5 c schematically show further variants of the invention. The arrangement shown in FIG. 5 a corresponds in its basic structure and mode of operation to the preceding devices. The difference to the preceding devices resides in FIG. 5 a in the provision between the rotary parts 16 , 18 of a slide bearing in which the conical effective areas 16 b , 18 b are in direct contact. The rotary parts 16 , 18 are moreover in rotating connection with the carrier part 12 and the guide part 14 via not shown radial and axial bearings.
In contrast to FIG. 5 a , the slide bearings illustrated in FIGS. 5 b and 5 c between the rotary parts 16 , 18 are not realized using corresponding conical effective areas 16 b , 18 b . Rather, the effective area 16 b of the rotary part 16 is configured in FIG. 5 b roughly in the shape of a sphere and in sliding contact with an effective area 18 b of the rotary part 18 of concave shape. In contrast thereto, the effective area 16 b of the rotary part 16 in FIG. 5 c is configured as a surface in the shape of a spherical disk and projects into an effective area 18 b configured as a surface in the shape of a conical socket. | The invention relates to a wheel suspension for a motor vehicle, comprising a wheel-side carrier part ( 12 ) holding a vehicle wheel ( 1 ) in a rotatable manner, and an axle-side guiding part ( 14 ) between which mutually rotating rotary parts ( 16, 18 ) are arranged. The guiding part ( 14 ), the rotary parts ( 16, 18 ) and/or the carrier part ( 12 ) interact with first and second effective areas ( 18 a, 36 a; 18 b, 16 b; 16 a, 54 a ) facing each other. According to the invention, the first effective area radially defines a conical or spherical hollow profile into which the corresponding second effective area protrudes in an essentially form-fitting manner. | 1 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation application under 35 U.S.C. §120 of co-pending U.S. patent application Ser. No. 14/657,423, filed Mar. 13, 2015, now U.S. Patent Application Publication No. 2015/0183357, which is a divisional application under 35 U.S.C. §121 of U.S. patent application Ser. No. 14/298,279, filed Jun. 6, 2014, now U.S. Pat. No. 9,039,097, which issued on May 26, 2015, which is a continuation application under 35 U.S.C. §120 of U.S. patent application Ser. No. 13/950,141, filed Jul. 24, 2013, now U.S. Pat. No. 8,746,805, which issued on Jun. 10, 2014, which is a continuation application under 35 U.S.C. §120 of U.S. patent application Ser. No. 13/647,870, filed Oct. 9, 2012, now abandoned, which is a continuation application under 35 U.S.C. §120 of U.S. patent application Ser. No. 12/709,231, filed Feb. 19, 2010, now abandoned, which claims the benefit under 35 U.S.C. §119 (e) of U.S. Provisional Patent Application No. 61/153,969, filed Feb. 19, 2009, the entire disclosures of which are incorporated by reference herein.
FIELD OF THE INVENTION
[0002] The present invention relates to the field of transportable containers, and more specifically, to an apparatus and method for remotely locking and unlocking a container adapted for transport upon one or more vehicles.
BACKGROUND OF THE INVENTION
[0003] Bulk materials, hazardous waste materials and other such materials are frequently transported to their destinations in very large waste handling containers. It is important that the door, often a rear, one piece door hingedly mounted at the top, maintain a fluid-tight seal against the container body to prevent the flowable materials from escaping during transport. The door sealing mechanisms can be difficult to operate, and the vehicle driver may have to latch, unlatch or adjust the door locking mechanisms in inclement weather. It is therefore desirable to provide a door locking mechanism for such containers that reduces the need for the driver to leave the vehicle cab, especially during container dumping action.
[0004] Oftentimes, the above described containers are desired to be intermodal. That is, it is desired that they be capable of being transported by a number of different vehicles, such as, for example, a truck, a train or a ship. The locking mechanism should accommodate all such forms of transport.
[0005] What is desired is a waste and material hauling container having a rear-mounted dump door with a remotely operable locking mechanism.
SUMMARY OF THE INVENTION
[0006] According to one embodiment, the present invention comprises a system comprising a container. The container has at least one open end and a door pivotably coupled to the container so that the door is movable between a first position, at which the door is spaced from the at least one open end, and a second position, at which the door closes the at least one open end. A locking assembly is coupled with the container and comprises a first shaft and a second shaft generally parallel with and spaced apart from the first shaft. The locking assembly also includes at least one over center linkage extending between a respective first pivotal connection between the at least one over center linkage and the first shaft and a respective second pivotal connection between the at least one over center linkage and the second shaft. Further, the locking assembly includes at least one latch coupled with the second shaft and movable between an unlatched position, wherein the at least one latch is spaced from the door, and a latched position, wherein the latch applies a closing force to the door. The at least one over center linkage is movable, when the door is at the second position, over center to a state at which the latch is in the latched position and the door is biased toward the second position.
[0007] In yet another embodiment, the present invention comprises a system comprising a container having at least one open end. A door is coupled to the container so that the door is movable between a first position, at which the door is spaced from the at least one open end, and a second position, at which the door closes the at least one open end. A locking assembly is coupled with the container, and the locking assembly comprises a first rotatable member, a second rotatable member, and a linkage assembly coupled between the first rotatable member and the second rotatable member. The linkage assembly has a first arm coupled to the first rotatable member, a second arm coupled to the second rotatable member, and a third arm coupled between the first and second arms at respective first and second pivot points. The locking assembly also comprises a latch coupled with the second rotatable member and movable between an unlatched position, wherein the at least one latch is spaced from the door, and a latched position, wherein the latch applies a closing force to the door. When the door is in the second position, a line passes through the second pivot point and the coupling between the first arm and the first rotatable member. When the first pivot point has rotated from a first side of the line to a second side of the line, the first pivot point is biased away from the first line, and the latch is in the latched position.
[0008] According to a further embodiment, the present invention comprises a system comprising a container having at least one open end and a door pivotably coupled to the container so that the door is movable between a first position, at which the door is spaced from the at least one open end, and a second position, at which the door closes the at least one open end. The system also comprises a locking assembly coupled with the container. The locking assembly comprises a first member, a second member, and a linkage assembly coupled between the first member and the second member. The linkage assembly has a first end coupled to the first member, a second end coupled to the second member, and at least one pivot point intermediate the first and second ends of the linkage assembly. The locking assembly also comprises a latch coupled with the second member and movable between an unlatched position, wherein the at least one latch is spaced from the door, and a latched position, wherein the latch applies a closing force to the door. When the at least one pivot point rotates to a point above the coupling of the linkage assembly first end and the first member, the door is in the second position, and wherein the door is released from the second position when the at least one pivot point is rotated below the coupling of the linkage assembly first end and the first member.
[0009] Further objects and advantages of the present invention will become apparent from the following description of the preferred embodiment.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] FIG. 1 is a side, elevational view of a container and vehicle combination 10 with apparatus 11 for remotely locking and unlocking the container door 12 , in accordance with the present invention, and with elements removed from the vehicle 13 for clarity.
[0011] FIG. 2 is a fragmented plan view of the rear portion of vehicle 13 of the container and vehicle combination 10 of FIG. 1 .
[0012] FIG. 3 is a rear, elevational view of container 14 of the container and vehicle combination 10 of FIG. 1 and shown in the locking position.
[0013] FIGS. 4-7 are side, cross-sectional views of the container 14 of FIG. 3 taken along the line 4 - 4 and viewed in the direction of the arrows and shown mounted upon vehicle 13 with locking assembly 95 in various stages of engagement with actuator assembly 33 and with certain parts removed or revealed for purposes of description.
[0014] FIG. 8 is a perspective view of the locking assembly 95 of the container and vehicle 13 combination 10 of FIG. 1 , and with one of the locking assembly sets 117 removed for clarity.
[0015] FIG. 9 is a bottom view of the container 14 of the container and vehicle combination 10 of FIG. 1 .
DESCRIPTION OF THE PREFERRED EMBODIMENT
[0016] For the purposes of promoting an understanding of the principles of the invention, reference will now be made to the embodiment illustrated in the drawings and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the invention is thereby intended, and alterations and modifications in the illustrated device, and further applications of the principles of the invention as illustrated herein are contemplated as would normally occur to one skilled in the art to which the invention relates.
[0017] Referring to FIG. 1 there is shown a container and vehicle combination 10 with apparatus 11 for remotely locking and unlocking the container door 12 , in accordance with the present invention. Combination 10 generally includes a vehicle 13 and a container 14 , the container's dump door 12 being rear-mounted, and the apparatus 11 being remotely operable to lock and unlock door 12 in fluid tight engagement with its container 14 .
[0018] The vehicle is a suitable container hoist having a main frame 17 and a tipper frame 18 hingedly connected to main frame 17 at hinge 19 . Suitable hydraulic cylinders (one shown at 20 ) connected between main frame 17 and tipper frame 18 and with the hydraulic system of vehicle 13 are operable to pivot tipper frame 18 between a reclined, container loading and transport position 23 ( FIGS. 4-7 ) and an inclined, dumping position 24 ( FIG. 1 ), as is known. Vehicle 13 is configured to receive and handle intermodal containers, that is, containers of a specific size and having corner blocks 25 at each of its eight corners to enable such container to be stacked for transport aboard other vessels, such as trains and ships. Alternative embodiments are contemplated wherein the container 14 is of other, non-intermodal configurations, and the apparatus 11 will nevertheless operate to remotely lock and unlock the container aboard a properly equipped vehicle.
[0019] Referring to FIG. 2 , vehicle 13 includes long rails 26 and 27 , numerous transverse cross-members, as at 28 and 29 , extending between long rails 26 and 27 , bolsters (one shown at 30 , FIG. 8 ) connected to the rear ends of and outwardly of long rails 26 and 27 , and the actuator assembly 33 of apparatus 11 , as described herein. Container 14 is configured to be loaded upon vehicle 13 , resting primarily upon long rails 26 and 27 and bolster 30 , and with the locking assembly 95 of apparatus 11 (as described herein) positioned directly above actuator assembly 33 for operative engagement therewith.
[0020] Referring to FIGS. 1 and 3 , container 14 is a rectangular box container with a rear opening 34 and with its rear door 12 being hingedly mounted at the top edge thereof by hinges 35 to enable door 12 to swing open of its own accord by gravity when the locks holding it are released and tipper frame 18 is pivoted to the inclined, dumping position 24 , as shown in FIG. 1 . Container 14 includes a seal 32 ( FIG. 4 ) held around the periphery of door opening 34 , and door 12 includes a sealing ridge 36 extending forwardly and into seal 32 when door 12 is drawn in to its closed position ( FIG. 4 ). Container 14 is provided with both bottom and side lock mechanism 37 , 38 and 39 (bottom) and 41 and 42 (side). Bottom lock mechanisms 37 , 38 and 39 are mutually identical, and only lock mechanism 38 will be fully described. Likewise, side mechanisms 41 and 42 are identical, albeit mirror images of each other, and only lock mechanism 41 will be fully described.
[0021] Referring to FIGS. 3 and 4 , side lock mechanism 41 includes an outwardly extending door pull pin 46 , a pull pin hook 47 , a rocker link 48 and a bar link 49 . Door pull pin 46 is rigidly connected to and extends laterally outwardly of door 12 . At its rear, container 13 includes two, opposing vertical box tubing members 51 and 52 , each of which defines an opening 54 and 55 , respectively, through which freely extends a corresponding door pull pin hook 47 and 56 , respectively. On opposing sides of tubing member 51 are mounted matching arrow plates 59 and 60 , which together close off the sides of opening 54 . Arrow plates 59 and 60 define aligned holes for receiving a pin 61 , about which is rotatably mounted triangular rocker link 48 , as shown. Rocker link 48 has three triangularly spaced mounting points, the second being at 62 where it is rotatably mounted to the forward end of door pull pin hook 47 , and the third being at 63 where it is rotatably mounted to the upper end of bar link 49 . The lower end of bar link 49 is pivotally connected to output pin 65 of locking assembly 95 , as described herein. Up and down motion of bar link 49 moves pull pin hook 47 between a relaxed, unlocked position 66 ( FIG. 6 ) and a retracted, locked position 67 ( FIG. 4 ) wherein the upturned hook 69 at the outer end of pull pin hook 47 has moved up, under door pun pin 46 and drawn door 12 tightly against its seal 32 .
[0022] At its bottom edge, door 12 is drawn and held closed by the three, identical lock mechanisms 37 - 39 . Lock mechanism 38 includes an adjustable door tensioner assembly 74 and an adjustable hook 75 that moves between a lowered unlocked position 76 ( FIGS. 6 and 7 ) and a raised and retracted locking position 77 ( FIG. 4 ). Tensioner assembly 74 includes a locking plate 80 , a set screw 81 and a locking nut 82 . Locking plate 80 is hingedly connected to door 12 at hinge 84 ( FIG. 7 ) and initially lays flat against the lower frame member 83 of door 12 . When adjustable hook 75 is pulled and angled upwardly, its hook tab 85 , rigidly secured to the upturned hook end of hook 75 , bears against locking plate 80 and pulls the bottom of door 12 inwardly, against seal 32 . In the event adjustment is ever needed to draw door 12 or just one portion of door 12 in tighter (for example, if the seal 32 wears unevenly or door 12 becomes warped), locking nut 82 can be loosened, and set screw 81 tightened. That is, set screw 81 is threadedly advanced through a threaded hole in locking plate 80 until its forward, leading end bears against the lower frame member 83 of door 12 , which pivots locking plate 80 about its hinge 84 and away from lower frame member 83 . When hook 75 is pulled in (forwardly), it bears against a now more rearwardly extending locking plate 80 , and door 12 is forced more tightly against its seal 32 . Locking nut 82 is re-tightened after the adjustment is complete. Adjustable hook 75 is shaped as shown, and includes an arcuate camming bump 88 , whereat hook 75 rides upon a bump pin 89 . The combination of the camming bump 88 on bump pin 89 and the both curved and linear input to the forward end 90 of hook 75 provides an up and around lock engaging motion relative to tensioner assembly 74 that provides plenty of clearance for door 12 to open and close and provides a reliable and tight door locking action.
[0023] Referring to FIGS. 2 and 4-9 , the apparatus 11 for remotely locking and unlocking the container door 12 generally includes actuator assembly 33 and locking assembly 95 . Actuator assembly 33 includes a push assembly 96 and a driving mechanism 97 to move push assembly 96 between an extended position 98 ( FIG. 6 ) and a retracted position 99 ( FIG. 4 ). Push assembly 96 includes a pair of generally U-shaped, spaced apart push plates 103 and 104 that are connected together by a spanner plate 105 ( FIG. 2 ) and a support beam 106 ( FIG. 6 ), both extending therebetween. Each push plate has a front and rear upstanding push arm 107 and 108 ( FIG. 5 ) configured to engage with a drive input rod ( 153 and 154 ) of the locking assembly 95 . Front push arm 107 has a rearward engagement surface 110 that slants up and rearwardly about 5 degrees. Rear push arm 108 has a forward engagement surface 111 that slopes up and rearwardly about 5 degrees, but its top portion includes an initial locking engagement surface 112 with a forward angle of about 30 degrees. Alternative embodiments are contemplated wherein the rearward and forward engagement surface angles vary to between about 3 and 8 degrees rearwardly and the initial locking engagement surface angle varies between about 20 degrees and 40 degrees. The forward bending surface portion 112 is generally straight, as are the front and rear engagement surfaces 110 and 112 , but alternative embodiments are contemplated wherein these surfaces have some degree of curvature. The initial locking engagement surface 112 fosters a smooth initial engagement with the main drive rods 153 and 154 , as described, herein, since these rods 153 and 154 may be rotated via their connector links 155 - 158 to near a state pointing almost directly to the rear. In the embodiment shown in FIG. 7 , with hook 75 in the lowered unlocked position 76 , the radial line 159 from the pivot axis of links 155 - 158 (that is, of main drive shaft 142 ) to their main drive rods 153 , 154 forms an angle of about 27 degrees below horizontal. In such configuration, with the force vector 160 of forward engagement surface 111 slanting up about 5 degrees, the horizontal movement of push plates 103 and 104 , upon engagement with main drive rods 153 and 154 , could bind up. The force vector 161 of forward sloping surface 112 is about 30 downward, which works to avoid such undesirable resistance by converting the initial force vector from about 5 degrees above horizontal to about 30 degrees below horizontal, as shown.
[0024] Driving mechanism 97 is a hydraulic cylinder 182 anchored at its forward end 183 to tipper frame 18 , and its output rod 184 is mounted to the support beam 106 of push assembly 96 . Appropriate guide structure and wear plates, as at 113 and 114 are provided to maintain push assembly 96 in its intended path.
[0025] Referring to FIGS. 4-9 , and particularly 8 and 9 , locking assembly 95 is contemplated to include one, two or more sets of components, each set configured and operable, upon engagement with actuator assembly 33 , to move its adjustable hook 75 between its lowered unlocked position 76 ( FIGS. 6 and 7 ) and its raised and retracted locking position 77 ( FIG. 4 ). As shown in FIGS. 8 and 9 , locking assembly 95 of the present invention has three hooks 75 and thus three, substantially identical locking assembly sets 115 , 116 and 117 . Locking assembly set 117 is removed from FIG. 8 tor discussion of surrounding components. Because locking assembly sets 115 , 116 and 117 are substantially identical, only set 116 will be described, with one notable difference discussed herein. Locking assembly set 116 includes its adjustable hook 75 , the forward end of which is adjustably connected to a hook rod 121 , which is rotatably journaled to both (1) one end of a pair of bent dogbone linkages 122 and (2) one end of a pair of upper links 123 . The opposite ends of the upper links 123 are fixed to rotate with an upper locking rod 126 , which is journaled for rotation by a pair of opposing lock assembly support plates 127 and 128 , as described herein. This upper locking rod 126 generally serves no other function than to support the links and rods connected thereto. However, upper locking rods 130 and 131 of the other two locking assembly sets 115 and 117 on opposite sides thereof not only support the connected linkages, but they also extend outwardly therefrom and connect with corresponding links 132 and 133 , respectively, which in turn connect with respective bar links 50 ( FIGS. 1 ) and 49 ( FIG. 4 ) to lock/unlock side lock mechanisms 42 and 41 .
[0026] At their forward ends, the pair of bent dogbone linkages 122 define aligned holes and are rigidly connected together by a sleeve 136 which, together, form a mounting collar 137 that is disposed between and journaled to and between one end of main drive links 140 and 141 . The opposing ends of main drive links 140 and 141 are rigidly connect to and rotate as a unit with main drive shaft 142 , which is supported for rotation by all the lock assembly support plates 127 and 128 , 145 and 146 , and 147 and 148 . Outside of and on opposing sides of the central pair of lock assembly support plates 127 and 128 , there are disposed main drive rods 153 and 154 , each rigidly connected via a pair of connector links 155 and 156 , and 157 and 158 , respectively to main drive shaft 142 , as shown.
[0027] Forward or rearward, generally linear input to main drive rods 153 and 154 (via rear and front upstanding push arms 108 and 107 ) causes main drive shaft 142 to rotate as a unit therewith and with main drive links 140 and 141 , which moves bent dogbone links 122 , which rotates upper links 123 and moves hook 75 . The rotation of main drive shaft 142 likewise moves hooks 75 of locking assembly sets 115 and 117 and rotates upper locking rods 130 and 131 , which moves link bars 50 and 49 via intermediate links 132 and 133 .
[0028] The bend in dogbone link 122 causes collar 137 and its axis of rotation to move over center when push assembly 96 is moved to the locking position 99 . The resistance to being locked tightly against its seal 32 causes door 12 to pull dogbone linkage 122 rearwardly, but because the axis of sleeve 136 of collar 137 is above a line extending between the axis of main drive shaft 142 and the axis of rotation at the opposite end of dogbone linkage 122 (that is, hook rod 121 ) the rearward pull on dogbone linkage 122 merely urges dogbone linkage 122 to rotate further counterclockwise about main drive shaft 142 , that is further to the locked position. The linkages thus resist becoming unlocked without the significant input of actuator assembly 33 .
[0029] A variety of part sizes, angles and manners of assembly and mounting may be used, but the current configuration is believed to be preferred.
[0030] Locking assembly 95 is supported by the three pairs of opposing lock assembly support plates 127 and 128 , 145 and 146 , and 147 and 148 , as well as the outer lock assembly support plates 162 and 163 , as shown in FIG. 8 . All the lock assembly support plates 127 , 128 , 144 - 148 , 162 and 163 are identical and are rigidly connected to rear and front bolsters 30 and 166 , as shown. Referring to just one of the lock assembly support plates, plate 147 comprises a strong flat plate with two inverted, generally T-shaped notches 169 defined therein. At the base (top) of each notch is defined a semi-circular recess 170 . A complementary-shaped, removable bearing T-plate 172 has defined at its base (top) a mirror image semi-circular recess 174 that, with recess 170 when T-plate 172 is positioned in a complementary notch 169 , forms a bearing hole 175 for rotatably supporting a rotating rod such as main drive shaft 142 or an upper locking rod 126 , 130 or 131 . Each T-plate is stitch welded to its lock assembly support plate (i.e. 147 ) which fixedly connects T-plate and support plate together, but which enables the stitch welds to be removed by known methods, if desired, to service locking assembly 95 . Assembly is also greatly facilitated as locking assembly 95 can be assembled upside down and the various linkages can be lowered into place, and the T-plates then stitch welded in place to provide a strong, secure and reliable locking assembly 95 . The entire locking assembly 95 collection is then turned over, for example as shown in FIG. 8 , and connected to or assembled with the rest of the container, the floor of the container typically being then welded directly thereon.
[0031] As assembled, when a container with locking assembly 95 is positioned atop a vehicle having actuator assembly 33 , the main drive rods 153 and 154 are each thus juxtaposed directly between the front and rear upstanding push arms 107 and 108 of a push assembly 96 . Actuation of actuator assembly 33 causes push assembly 96 to engage drive rods 153 and 154 and thus move locking hooks 75 and, if the container 14 is so equipped, side pull pin hooks 47 into and out of their locking positions.
[0032] Container and vehicle combination 10 is further provided with one or more auxiliary locks, such as Stinger locks 177 and 178 , as is known.
[0033] While the invention has been illustrated and described in detail in the drawings and foregoing description, the same is to be considered as illustrative and not restrictive in character, it being understood that only the preferred embodiment has been shown and described and that all changes and modifications that come within the spirit of the invention are desired to be protected. | A system including a container having a door pivotably coupled to the container that is movable between a first position and a second position. A locking assembly is coupled with the container and includes a first shaft and a second shaft generally parallel with and spaced apart from the first shaft, and an over center linkage extending between a respective first pivotal connection between the over center linkage and the first shaft and a respective second pivotal connection between the over center linkage and the second shaft. Further, the locking assembly includes at least one latch coupled with the second shaft and movable between an unlatched position and a latched position. The over center linkage is movable, when the door is at the second position, over center to a state at which the latch is in the latched position and the door is biased toward the second position. | 1 |
FIELD OF THE INVENTION
[0001] The present invention relates in general to biopsy devices, and more particularly biopsy devices having a cutter for severing tissue, and even more particularly to biopsy ices for multiple sampling with a probe remaining inserted.
BACKGROUND OF THE INVENTION
[0002] When a suspicious tissue mass is discovered in a patient's breast through examination, ultrasound, MRI, X-ray imaging or the like, it is often necessary to perform a biopsy procedure to remove one or more samples of that tissue in order to determine whether the mass contains cancerous cells. A biopsy may be performed using an open or percutaneous method.
[0003] An open biopsy is performed by making a large incision in the breast and removing either the entire mass, called an excisional biopsy, or a substantial portion of it, own as an incisional biopsy. An open biopsy is a surgical procedure that is usually done as an outpatient procedure in a hospital or a surgical center, involving both high cost and a high level of trauma to the patient. Open biopsy carries a relatively higher risk of infection and bleeding than does percutaneous biopsy, and the disfigurement that sometimes results from an open biopsy may make it difficult to read future mammograms. Further, the aesthetic considerations of the patient make open biopsy even less appealing due to the risk of disfigurement. Given that a high percentage of biopsies show that the suspicious tissue mass is not cancerous, the downsides of the open biopsy procedure render this method inappropriate in many cases.
[0004] Percutaneous biopsy, to the contrary, is much less invasive than open biopsy. percutaneous biopsy may be performed using fine needle aspiration (FNA) or core needle biopsy. In FNA, a Very thin needle is used to withdraw fluid and cells from the suspicious tissue mass. This method has an advantage in that it is very low-pain, so low-pain that local anesthetic is not always used because the application of it may be more painful than the FNA itself. However, a shortcoming of FNA is that only a small number of cells are obtained through the procedure, rendering it relatively less useful in analyzing the suspicious tissue and making an assessment of the progression of the cancer less simple if the sample is found to be malignant.
[0005] During a core needle biopsy, a small tissue sample is removed allowing for a pathological assessment of the tissue, including an assessment of the progression of any cancerous cells that are found. The following patent documents disclose various core biopsy devices and are incorporated herein by reference in their entirety: U.S. Pat. No. 6,273,862 issued Aug. 14, 2001; U.S. Pat. No. 6,231,522 issued May 15, 2001; U.S. Pat. No. 6,228,055 issued May 8, 2001; U.S. Pat. No. 6,120,462 issued Sep. 19, 2000; U.S. Pat. No. 6,086,544 issued Jul. 11, 2000; U.S. Pat. No. 6,077,230 issued Jun. 20, 2000; U.S. Pat. No. 6,017,316 issued Jan. 25, 2000; U.S. Pat. No. 6,007,497 issued Dec. 28, 1999; U.S. Pat. No. 5,980,469 issued Nov. 9, 1999; U.S. Pat. No. 5,964,716 issued Oct. 12, 1999; U.S. Pat. No. 5,928,164 issued Jul. 27, 1999; U.S. Pat. No. 5,775,333 issued Jul. 7, 1998; U.S. Pat. No. 5,769,086 issued Jun. 23, 1998; U.S. Pat. No. 5,649,547 issued Jul. 22, 1997; U.S. Pat. No. 5,526,822 issued Jun. 18, 1996; and U.S. Patent Application 2003/0199753 published Oct. 23, 2003 to Hibner et al.
[0006] At present, a biopsy instrument marketed under the tradename MAMMOTOME is commercially available from ETHICON ENDO-SURGERY, INC. for use in obtaining breast biopsy samples. These devices generally retrieve multiple core biopsy samples from one insertion into breast tissue with vacuum assistance. In particular, a cutter tube is extended into a probe to cut tissue prolapsed into a side aperture under vacuum assistance and then the cutter tube is fully retracted between cuts to extract the sample.
[0007] With a long probe, the rate of sample taking is limited not only by the time required to rotate or reposition the probe but also by the time needed to translate the cutter. As an alternative to this “long stroke” biopsy device, a “short stroke” biopsy device is described in the following commonly assigned patent applications: U.S. patent application Ser. No. 10/676,944, “Biopsy Instrument with Internal Specimen Collection Mechanism” filed Sep. 30, 2003 in the name of Hibner et al.; and U.S. patent application Ser. No. 10/732,843, “Biopsy Device with Sample Tube” filed Dec. 10, 2003 in the name of Cicenas et al. The cutter is cycled across the side aperture, reducing the sample time. Several alternative specimen collection mechanisms are described that draw samples through the cutter tube, all of which allow for taking multiple samples without removing the probe from the breast.
[0008] Even given the many advantages of such multiple sample taking core biopsy devices, in certain applications some surgeons continue to use less expensive biopsy devices guided in real time by an ultrasonic system. These simple biopsy systems omit a full function control console that operates the cutter and vacuum assistance. Instead, a manually controlled hand piece advances a cutter by either stored spring force, a constant pneumatic pressure source, or motor power. Then the surgeon activates a cutter motor to effect the tissue sample. Thus, the surgeon is challenged to maintain the biopsy probe at a desired surgical site while manipulating the patient's breast.
[0009] Consequently, it would be desirable to provide for a core biopsy device with a motorized cutter that provides increased functionality such as one-handed operation with assisted multiple sample retrieval with only one insertion of the probe, yet be able to retain the economical aspects of simple core biopsy devices that lack elaborate remote control systems.
[0010] Spring-fired core needle biopsy devices rely upon a firing mechanism that thrusts forward a needle and a cutter to penetrate the tissue and to obtain a tissue sample rather than palpitating tissue to prolapse into a side aperture of a probe. Frequently, a surgeon may encounter an area of dense tissue that is more difficult to penetrate than the surrounding tissue during core needle biopsy. In particular, the lesion or tissue mass being targeted in the biopsy procedure may be difficult to penetrate, requiring the physician to push the biopsy needle with considerable force and/or speed in an attempt to penetrate the lesion and collect a sample.
[0011] When encountering such an area of dense tissue, it is common for surgeons using the type of firing core needle biopsy device described above to fire the device in order to penetrate the lesion and obtain a sample. However, due to the length of the firing stroke of such devices, which may be as long as 0.75 inches, it is nearly impossible for the surgeon to control the travel of the needle after firing. Consequently, the long needle stroke may cause uncertainty as to the needle tip location post fire. This may cause the surgeon to obtain a sample from the wrong area. In addition to missing the targeted tissue, long firing strokes may cause the needle to puncture the chest wall or pierce the skin, particularly when the targeted area is near the patient's chest wall. Even if the skin is not pierced, the long travel of the needle, along with the likelihood that the needle will be pushed off course by the force of the firing stroke, may lead to needlessly increased trauma for the patient. These spring-fired biopsy devices also yield a single sample per insertion, thus limiting the amount of diagnostic and therapeutic treatment that may be achieved without the increased discomfort and tissue trauma from repeated insertions. Based on surgeons' use of the long firing stroke feature of current devices to aid in penetrating tissue lesions, it is clear that the medical community sees the benefit of firing assistance when inserting a probe to the desired location.
[0012] In commonly-owned and co-pending U.S. patent application Ser. No. 11/035,873, BIOPSY INSTRUMENT WITH IMPROVED NEEDLE PENETRATION to Beckman, et al., filed on Jan. 10, 2005, manual mechanisms are disclosed that impart small reciprocating motions to the probe of a core biopsy device to render assistance in penetrating tissue, yet cutting is performed after the probe is properly positioned, thus avoiding taking samples from the wrong location. While there are advantages to having such cutting assistance imparted by manual actuation, it is generally desirable to alleviate the need for the surgeon to perform this additional action while having to manually position the biopsy device.
[0013] Additionally, it would be desirable to provide for a hand-held core biopsy device that automatically imparts a motion to the probe that assists in penetrating dense tissue yet does not take a sample.
SUMMARY OF THE INVENTION
[0014] The present invention addresses these and other problems of the prior art by providing a core biopsy device having a probe assembly with a probe support structure that holds a probe having a side aperture. A cutter tube is slidingly received by the probe and sized to translate across the side aperture to sever prolapsed tissue. A hand piece includes a hand piece support structure having a lateral engaging portion that receives the probe assembly. A lead screw is attached for rotation to the hand piece support structure. A cutter carriage is longitudinally translated by rotation of the lead screw thereby translating the cutter tube. Thereby, an economical incorporation of a replaceable probe and cutter tube into a laterally mounted assembly allows reuse of a powered hand piece.
[0015] In one aspect consistent with other aspects of the invention, a biopsy device includes a frame supported core biopsy probe, the frame spring biased to a housing. A motor driven cam wheel coupled to the housing urges the frame against the spring bias, imparting a reciprocating longitudinal movement to the core biopsy probe to assist in penetrating dense tissue.
[0016] In another aspect of the invention, a biopsy device includes the replaceable probe assembly that engages a motor-driven carriage assembly that sequences distal translation of a rotated cutter tube with vacuum assistance sequenced from a constant vacuum source by the position of the cutter tube. Thereby, advantages of consistent prolapse of tissue into the probe is achieved with a commonly available vacuum source.
[0017] In yet another aspect of the invention, a biopsy device obtains tissue samples that prolapse into a sample aperture in a probe needle that are then severed by a translating cutter tube received in the probe needle. A sample straw is proximally received in the cutter tube to capture these severed tissue samples. As these severed tissue samples are sequentially stacked in the sample straw, an indicator tube is forced proximally out of the sample straw to give a visual indication as to the number of tissue samples obtained. The stored tissue samples advantageously are maintained in the order taken, which aids in further diagnostic assessment.
[0018] In yet a further aspect of the invention, a biopsy device obtains tissue samples that prolapse into a sample aperture in a probe needle that are then severed by a translating cutter tube received in the probe needle. A storage tube communicates with a proximal end of the cutter tube so that a vacuum control may apply a vacuum through the storage tube and the cutter tube to retract severed tissue samples there through. The stored tissue samples are also advantageously maintained in the order taken to aid in further diagnostic assessment.
[0019] In yet an additional aspect of the invention, a hand piece has a hand piece support structure having a lateral engaging portion operatively configured to engage a probe support structure of a selected one of a first and second probe assemblies. A lead screw translates a cutter carriage that advances a cutter tube within a probe needle of the selected probe assembly. One probe assembly includes a sample straw that is proximally advanced by a cutter carriage of the hand piece that is longitudinally translated by rotation of the lead screw to retract tissue samples. The other probe assembly has a storage tube that communicates with the cutter tube for pneumatically retracting tissue samples. Thereby, economical incorporation of a common hand piece may be realized while providing the clinical flexibility of choosing a disposable probe assembly with a desired approach to tissue sample retraction.
[0020] In yet another aspect of the invention, a method of obtaining core biopsy samples adantageously maintains samples taken in a sequential stack to enhance diagnostic assessment thereof. This orientation is achieved by inserting a core biopsy needle into tissue, prolapsing tissue into an opening of the core biopsy needle and then translating a cutter tube through the core biopsy needle to sever the prolapsed tissue to form a first tissue sample. These steps are repeated with each tissue sample being sequentially urged into a sample lumen that proximally communicates with the cutter tube. Thereby, the sequential stacking is maintained for lateral retrieval and analysis.
[0021] These and other objects and advantages of the present invention shall be made apparent from the accompanying drawings and the description thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] While the specification concludes with claims particularly pointing out and distinctly claiming the present invention, it is believed the same will be better understood by reference to the following description, taken in conjunction with the accompanying drawings in which:
[0023] FIG. 1 is a top perspective view of a biopsy device with a disposable probe assembly detached from a reusable hand piece, the latter with a housing shown in phantom;
[0024] FIG. 2 is a bottom perspective view of the biopsy device of FIG. 1 ;
[0025] FIG. 3 is a disassembled perspective view of the disposable probe assembly FIG. 1 ;
[0026] FIG. 4 is a disassembled perspective view of the reusable hand piece of FIG. of FIG. 1 ;
[0027] FIG. 5 is a top view of an assembled biopsy device of FIG. 1 ;
[0028] FIG. 6 is a front view of the biopsy device of FIG. 5 ;
[0029] FIG. 7 is a left side view in elevation of the biopsy device of FIG. 5 ;
[0030] FIG. 8 is a bottom view of the biopsy device of FIG. 5 ;
[0031] FIG. 9 is a front view of the biopsy device of FIG. 7 taken in cross section along lines 9 - 9 through a distal cutter carriage engagement to a cutter gear;
[0032] FIG. 10 is a front view of the biopsy device of FIG. 7 taken in cross section along lines 10 - 10 through a proximal straw carriage and stacking straw assembly;
[0033] FIG. 11 is a front view of the biopsy device of FIG. 7 taken in cross section along lines 11 - 11 through a bayonet locking member disengaged from the stacking straw assembly by attaching the disposable probe assembly to the reusable hand piece;
[0034] FIG. 12 is a bottom view of the biopsy device of FIG. 7 taken in horizontal cross section along lines 12 - 12 through the probe and stacking straw assembly;
[0035] FIG. 13 is a detail perspective view of a slide button, sliding spur gear, and tissue penetration gear of the biopsy device of FIG. 5 ;
[0036] FIG. 14 is a left side view of the probe inserted into tissue of the biopsy device of FIG. 12 in longitudinal cross section exposing the distally translated cutter tube, elongate straw, and indicator tube;
[0037] FIG. 15 is a left perspective view of the biopsy device of FIG. 12 with the housing removed;
[0038] FIG. 16 is a bottom view of the biopsy device of FIG. 6 taken in cross section along staggered lines 16 - 16 through a lead (translation) screw and a slide pin engaged to the cutter and straw carriages;
[0039] FIG. 17 is a bottom view of the biopsy device of FIG. 6 taken in horizontal cross section along lines 17 - 17 through a pneumatic valve that sequences vacuum assistance corresponding to cutter position;
[0040] FIG. 18 is a bottom of the biopsy device of FIG. 16 in cross section after proximal retraction of the straw carriage;
[0041] FIG. 19 is a left perspective detail view of the carriages, lead screw, and sliding pin of the biopsy device of FIG. 18 with the housing removed;
[0042] FIG. 20 is a left view in elevation of the probe in longitudinal cross section of the biopsy device of FIG. 18 with the elongate straw and indicator tube retracted;
[0043] FIG. 21 is a bottom of the biopsy device of FIG. 18 in cross section with both the cutter carriage and straw carriage retracted;
[0044] FIG. 22 is a left perspective detail view of the carriages, lead screw, and sliding pin of the biopsy device of FIG. 21 ;
[0045] FIG. 23 is a left view in elevation of the probe in longitudinal cross section of the biopsy device of FIG. 21 with vacuum assistance prolapsing tissue into the side aperture;
[0046] FIG. 24 is a bottom view of the pneumatic valve in horizontal cross section of the biopsy device of FIG. 21 ;
[0047] FIG. 25 is a left perspective detail view of the carriages, lead screw and sliding pin of the biopsy device of FIG. 21 after distal translation of the cutter carriage;
[0048] FIG. 26 is a left side view of the probe in longitudinal cross section of the biopsy device of FIG. 25 after severing tissue;
[0049] FIG. 27 is a left side view of the probe in longitudinal cross section of the biopsy device of FIG. 26 with distally translated cutter and straw carriages after taking two samples held in the elongate straw by bent up tabs with corresponding proximal extrusion of the indicator tube;
[0050] FIG. 28 is a left side detail view in elevation of a proximal portion of the stacking straw assembly including a mechanical diode preventing distal movement of the indicator tube into the elongate straw;
[0051] FIG. 29 is a perspective view of the straw carriage and an engaged stacking straw assembly;
[0052] FIG. 30 is a perspective view of the straw carriage and a disengaged stacking straw assembly;
[0053] FIG. 31 is an aft view in elevation of the biopsy device of FIG. 30 with the disengaged stacking straw assembly;
[0054] FIG. 32 is an aft view in elevation of the biopsy device of FIG. 29 with the stacking straw assembly rotated a quarter turn into engagement;
[0055] FIG. 33 is a perspective view of the stacking straw assembly of the biopsy device of FIG. 1 after removal and peeling apart to access samples;
[0056] FIG. 34 is a top perspective view of an alternative probe assembly with omitted vacuum assistance instead relying on external hand palpitation of tissue to prolapse the tissue into the side aperture of the probe for the biopsy device of FIG. I to acquire tissue samples;
[0057] FIG. 35 is a bottom perspective view of the alternative probe assembly of FIG. 34 ;
[0058] FIG. 36 is a disassembled perspective view of the alternative probe assembly FIG. 34 ;
[0059] FIG. 37 is a disassembled perspective view of an alternative disposable assembly with a straw assembly having a luer fitting for the reusable hand piece of FIG. 1 ;
[0060] FIG. 38 is a left side view of an alternative probe inserted into tissue for the reusable hand piece of FIG. 1 in longitudinal cross section exposing the distally translated cutter tube, elongate straw, and indicator tube and with through holes in a probe tube;
[0061] FIG. 39 is a left side view of another alternative probe inserted into tissue for the hand piece of FIG. 1 that employs pneumatic pressure to retrieve tissue samples through the cutter tube rather than a straw assembly;
[0062] FIG. 40 is a top left perspective view of an alternative proximal stacking disposable assembly incorporating the probe of FIG. 39 and being in an initial state before use;
[0063] FIG. 41 is a bottom right perspective view of the alternative proximal stacking disposable assembly of FIG. 40 ;
[0064] FIG. 42 is a disassembled perspective view of the alternative proximal stacking disposable assembly of FIG. 40 ;
[0065] FIG. 43 is a top left perspective view of the alternative proximal stacking disposable assembly of FIG. 40 with a retrieved tissue sample and a retracted cutter;
[0066] FIG. 44 is a bottom right perspective view of the alternative proximal stacking disposable assembly of FIG. 43 ;
[0067] FIG. 45 is a top left perspective view of a flexible, peel-apart external tissue lumen after actuating a lumen peel-apart tab to separate an inwardly open channel holding retrieved tissue samples from an elongate seal;
[0068] FIG. 46 is a left aft perspective view of the sample holding portion of the alternative proximal stacking disposable assembly of FIG. 40 with a distal portion transversely cut away to expose vacuum and tissue lumens;
[0069] FIG. 47 is a disassembled perspective of the sample holding portion of the alternative proximal stacking disposable assembly of FIG. 40 ;
[0070] FIG. 48 is a left perspective view of the sample holding portion of the alternative proximal stacking disposable assembly of FIG. 40 formed of a transparent material exposing retrieved tissue samples;
[0071] FIG. 49 is a top right perspective view of a reciprocating member of the sample holding portion of the alternative proximal stacking disposable assembly of FIG. 40 ;
[0072] FIG. 50 is a perspective view of a translating flexible rod of the sample holding portion of the alternative proximal stacking disposable assembly of FIG. 40 ;
[0073] FIG. 51 is a left side view in longitudinal cross section taken through the translating flexible rod of the sample holding portion of the alternative proximal stacking disposable assembly of FIG. 40 ;
[0074] FIG. 52 is a left perspective view of the sample holding portion of the alternative proximal stacking disposable assembly of FIG. 40 with a retracted reciprocating portion;
[0075] FIG. 53 is a left perspective view of the sample holding portion of the alternative proximal stacking disposable assembly of FIG. 40 with the reciprocating portion subsequently distally advanced; and
[0076] FIG. 54 is a left perspective view of the sample holding portion of the alternative proximal stacking disposable assembly of FIG. 40 with the reciprocating portion subsequently proximally retracted.
DETAILED DESCRIPTION OF THE INVENTION
[0077] In FIGS. 1-4 , a biopsy device 10 has a reusable hand piece 12 and a disposable probe 14 that enables economical taking of multiple percutaneous core biopsy samples by accessing a standard medical vacuum pump or wall-mounted vacuum access port (not shown) through an interfacing vacuum conduit 16 . In the illustrative version, the hand piece 12 is self-powered and suitable for use in conjunction with ultrasonic diagnostic imaging. The disposable probe 14 reduces the portion of biopsy device 10 that requires protective packaging to avoid contact with sharp surfaces and to keep it sterile prior to use. Further economy is accomplished by reducing the portion of the biopsy device 10 that is disposed as medical waste between uses. Movable components of the disposable probe 14 are advantageously locked until mounted in an access trough 18 formed in a housing 20 of the reusable hand piece 12 . It should be appreciated that one or more standard mechanical, pneumatic, or electrical latches (not shown) may be integrated into the biopsy device 10 to secure the disposable probe 14 to the reusable hand piece 12 .
[0078] With particular reference to FIG. 3 , the disposable probe assembly 14 includes a substantially rectangular cover 22 sized to close the access trough recess 18 ( FIGS. 2, 4 ). An end slot 24 formed in the cover 20 ( FIGS. 1-2 , 4 ) is closed by a probe union sleeve 26 attached to an inner surface 27 of the substantially rectangular cover 22 . A core biopsy needle (“probe”) assembly 28 passes longitudinally through the probe union sleeve 26 and is formed by a probe tube 30 with underlying vacuum lumen 32 that communicates with a side aperture 34 through holes 35 ( FIG. 23 ) near a distal opening 36 of the probe tube 30 that is closed by a piercing tip 38 . A cutter tube 40 is sized to closely fit and translate within an inner diameter (i.e., cutter lumen) of the probe tube 30 with a length sufficient to close the side aperture 34 with a proximal end 42 extending from the probe union sleeve 26 to attach to a cutter gear 44 , as depicted in FIG. 1 .
[0079] Proximal to the probe union sleeve 26 is an elongate slot 50 that is part of a vacuum assist valve assembly 52 . The cutter gear 44 includes distal and proximal annular recesses 54 , 56 flanking spur gear teeth 58 that engage the reusable hand piece 12 as described below. A more distal annular recess 60 is gripped by a post 62 that is engaged to longitudinally translate in an elongate post slot 64 of a distal portion 66 of a vacuum valve actuator 68 . A cylindrical proximal portion 70 of the vacuum valve actuator 68 has distal and proximal O-ring grooves 72 , 73 that respectively retain distal and proximal dynamic O-ring seals 74 , 75 that move within a distally open cylindrical valve bore 76 of a valve body 78 molded onto an outer surface 79 of the substantially rectangular cover 22 ( FIG. 2 ).
[0080] As described below, the vacuum valve actuator 68 selectively allows communication between a proximal port 80 , a center port 82 , and a distal port 84 ( FIG. 2 ). In particular, with the cutter gear 44 retracted, the proximal and center ports 80 , 82 are in communication. With the cutter gear translated distally, the center and distal ports 82 , 84 communicate. The center port 82 is attached to a distal vacuum conduit 86 whose other end is connected through the rectangular cover 22 to the probe union sleeve 26 . It should be appreciated that the probe union sleeve 26 includes pneumatic passages that communicate between a proximal end of the vacuum lumen 32 and the distal vacuum conduit 86 . The distal port 84 is attached to a hose nib 88 that is exposed to atmospheric pressure. Hose nib 88 may include an air and/or saline filter. Alternatively, hose nib 88 may be connected to a positive pressure source (e.g., fluid pump) or a negative pressure source (e.g., vacuum pump, syringe) to aspirate fluids. Likewise, hose nib 88 may be used to lavage the tissue cavity with saline, pain medication, or bleeding control fluids.. The proximal port 80 communicates through a proximal vacuum conduit 90 to the interfacing vacuum conduit 16 .
[0081] With further reference to FIG. 3 , a sample extraction feature is incorporated so that multiple samples may be made without the need to remove the probe assembly 28 from tissue nor even to full retract the cutter tube 40 to retract a tissue specimen to the reusable hand piece 12 . In the illustrative version, this feature is accomplished with a stacking straw assembly 100 . An elongate straw 102 is scored down its length on opposite sides by grooves 104 defining first and second straw halves 106 , 108 , whose respective proximal, outer surfaces 110 , 112 are attached to triangular grips 114 , 116 , respectively. A locking strip 118 extends distally from one triangular grip 114 and is attached along a proximal portion of the first straw half 106 .
[0082] Distal and proximal tabs 120 , 122 extend from the inner surface 27 of the substantially rectangular cover 22 , each having a respective through hole 124 , 126 through which the stacking straw assembly 100 is inserted. The through holes 124 , 126 are shaped to allow the locking strip 118 to rotate ninety (90) degrees. A bayonet locking member 130 also extends from the inner surface 27 of the substantially rectangular cover 22 just distal and laterally offset from the through hole 124 of the distal tab 120 to lock into an alignment locking slot 132 in the locking strip 118 when laterally rotated. The bayonet locking member 130 prevents axial movement of the stacking straw assembly 100 . The cutter gear 44 and cutter tube 40 cannot move proximally due to contact with the stacking straw assembly 100 and cannot move distally due to contact with the probe union sleeve 26 . By securing both the cutter gear 44 and the stacking straw assembly 100 in a full distal axial position, the disposable probe 14 is aligned to engage the components of the reusable hand piece 12 as described below. Distal to the alignment locking slot 132 , a rectangular recess 134 , formed in the locking strip 118 , defines a distal-most locking finger 136 for engaging components of the reusuable hand piece 12 that positions the stacking straw assembly 100 as described below. An indicator tube 150 has a stacked cone-shaped outer surface 152 ( FIG. 14 ) that slides within the elongate straw 104 that in turn slides within the cutter tube 40 .
[0083] With particular reference to FIG. 4 , the reusable hand piece 12 includes four user controls aligned on a top surface 160 of the housing 20 , specifically from most distal to most proximal: a forward motor rotation key 162 , a reverse motor rotation key 164 , a saline flush key 166 and a slide button 168 for selecting insertion mode or sample taking mode. The keys 162 - 166 control a control circuit 170 , which may include integral power storage (e.g., batteries, fuel cell, etc.) for untethered use. The forward motor rotation key 162 causes a DC motor 172 to rotate its motor output shaft 174 in a forward rotation. A slide spur gear 176 includes an internal keyed engagement with a longitudinal key groove 178 on the motor output shaft 174 that allows longitudinal positioning by the slide button 168 . In particular, fore and aft brackets 180 , 182 of the slide button 168 engage distal and aft annular grooves 184 , 186 that flank spur gear teeth 188 of the slide spur gear 176 .
[0084] When the slide button 168 is moved distally, the slide spur gear 176 engages a tissue penetration gear 190 that spins on a common shaft centerline 192 forward of a gearbox input gear 196 . Gearbox input gear 196 consists of a distal small gear 198 and a proximal large gear 200 . The tissue penetration gear 190 has spur gear teeth 206 that engage the slide spur gear 176 . A frame hub 212 projects proximally from the frame 204 with a strike pin 214 projecting upwardly from the frame hub 212 . In FIG. 4 and 13 , a circular cam wheel 216 is attached to a distal side of the tissue penetration gear 190 . Rotating the tissue penetration gear 190 urges the strike pin 214 , and thus the frame 204 , proximally. In FIG. 12 , left and right spring cavities 218 , 220 (when viewed from above), formed longitudinally in distal comers of the frame 204 , respectively receive inwardly projecting left and right tabs 222 , 224 from the cover 20 and receive left and right compression springs 226 , 228 . Movement of the frame 204 proximally compresses these compression springs 226 , 228 that thereafter assert a restoring force.
[0085] When the slide button 168 is moved proximally into engagement with the gearbox input gear 196 , specifically the distal small gear 198 , also engages and turns a translation large input gear 230 whose shaft 232 passes through an aft wall 234 of the frame 204 . The proximal large gear 200 of the gearbox input gear 196 engages and turns a rotation small input gear 236 whose shaft 238 passes through the aft wall 234 . The frame 204 includes a carriage recess 240 , defined between a partition 242 and the aft wall 234 , that contains longitudinally aligned left side lead (translation) screw 244 and right-side rotation spur gear 246 that are attached for rotation respectively with the shafts 232 , 238 . The partition 242 is positioned aft of the left and right tabs 222 , 224 of the cover 20 and also defines in part the left and right spring cavities 218 , 220 . An unlocking cam 247 projects proximally from and is longitudinally centered on the aft wall 234 above the position of the lead (translation) screw 244 and rotation spur gear 246 .
[0086] The rotation spur gear 246 engages the cutter gear 44 when the disposable probe 14 is inserted, imparting a rotation as the cutter tube 40 and cutter gear 44 translate longitudinally in response to the rotation of the lead (translation) screw 244 . This translation is caused by lead screw threads 248 . In particular, a distal cutter carriage 250 is longitudinally moved on the lead screw threads 248 . Distal and proximal J-hook extensions 252 , 254 project downwardly from the distal cutter carriage 250 to engage the distal and proximal annular recesses 54 , 56 of the cutter gear 44 ( FIG. 3 ). Distal of the cutter carriage 250 , a biasing spring 256 urges against the cutter carriage 250 , which assists in engagement of the lead screw threads 248 with the distal cutter carriage 250 . With reference to FIGS. 4 and 19 , a sliding pin 260 has a proximal carriage sliding pin retainer 266 attached to a proximal straw carriage 258 . Shaft 264 also passes through a distal carriage sliding pin retainer 270 attached to the distal cutter carriage 250 . Sliding pin 260 has a proximal end 262 and a distal end 268 to prevent the sliding pin 260 from disengaging from the carriage sliding pin retainers 266 , 270 . A sliding pin spring 272 resides on the sliding pin 260 and is constrained at each end by carriage sliding pin retainers 266 , 270 .
[0087] With the components FIGS. 1-4 now introduced, a sequence of use of the biopsy device 10 will be described. The interfacing vacuum lumen 16 is attached to the disposable probe assembly 14 ( FIGS. 1-2 ). The disposable probe assembly 14 is installed into the reusable hand piece 12 ( FIGS. 5-8 ). In so doing, the distal cutter carriage 250 engages the cutter gear 44 ( FIG. 9 ), the proximal straw carriage 258 engages the locking strip 118 of the stacking straw assembly 100 ( FIG. 10 ), and the bayonet locking member 130 is deflected by the unlocking cam 247 , longitudinally unlocking from the alignment locking slot 132 of the locking strip 118 ( FIG. 11 ) allowing longitudinal movement of the cutter tube 40 and the straw stacking assembly 100 .
[0088] In FIGS. 12, 14 , the cutter and straw carriages 250 , 258 may initially be distally advanced to close the side aperture 34 of its probe tube 30 with the cutter tube 40 and the stacking straw assembly 100 also fully distally advanced to minimize proximal extension of its elongate straw 102 .
[0089] In FIG. 13 , the piercing tip 38 of the core biopsy needle (probe) assembly 28 is assisted in penetrating tissue by moving the slide button 168 distally to a “tissue insertion mode” wherein the slide spur gear 176 engages the tissue penetration gear 190 . depression of the forward motor rotation key 162 turns these gears 176 , 190 causing the circular cam wheel 216 to turn against strike pin 214 that creates proximal longitudinal motion of frame 204 and core biopsy needle (probe) assembly 28 of approximately 0.1 inch at a rotation rate of 7 cycles per second. Left and right compression springs 226 , 228 provide the restoring distal longitudinal motion to frame 204 and disposable probe 14 as left and right compression springs 226 , 228 are repeatedly compressed between the forward surface of the left and right spring cavities 218 , 220 as the frame 204 and the left and right tabs 222 , 224 of the housing 20 . The restoring distal longitudinal motion to frame 204 and core biopsy needle (probe) assembly 28 result in a corresponding distal motion of piecing tip 38 that assists in penetrating tissue.
[0090] In FIG. 15 , with the side aperture 40 positioned within the tissue to take samples, the slide button 168 is moved proximally to engage the slide spur gear 176 with the distal small gear 198 of the gearbox input gear 196 . When the forward motor rotation key 162 is depressed, the DC motor 172 rotates in a forward direction, turning the slide spur gear 176 , which turns the distal small gear 198 that directly turns the translation large input gear 230 that is connected by the shaft 232 through the aft wall 234 of the frame 204 to the lead (translation ) screw 244 . Meanwhile, the proximal large gear 200 of the gearbox input gear 196 rotates the small input gear 236 that turns shaft 238 through aft wall 234 to turn the rotation spur gear 246 .
[0091] With the carriages 250 , 258 distally advanced as depicted in FIGS. 15-16 , the cylindrical proximal portion 70 of the vacuum valve actuator 68 is also distally positioned as depicted in FIG. 17 . The hose nib 88 is thus in fluid communication through the distal port 84 , through the distally open cylindrical valve bore 76 between distal and proximal dynamic O-ring seals 74 , 75 to the center port 82 through the distal vacuum conduit 86 to the vacuum lumen 32 .
[0092] In FIGS. 18-19 , depression of the reverse motor rotation key 164 causes the lead (translation) screw 244 to rotate in a reverse direction. Sliding pin spring 272 between the distal cutter carriage 250 and the proximal straw carriage 258 urges the proximal straw carriage 258 into engagement with the lead screw thread 248 , causing the straw carriage 258 to move proximally as the cutter carriage 250 free wheels on an unthreaded distal portion of the lead screw 244 . The straw carriage 258 draws back the elongate straw 102 and the indicator tube 150 ( FIG. 20 ). As the straw carriage 258 approaches the proximal portion of the lead screw 244 , the distal end 268 of sliding pin 260 contacts the distal carriage sliding pin retainer 270 on distal cutter carriage 250 , pulling the distal cutter carriage 250 onto the lead screw thread 248 . Thereafter, the cutter carriage 250 and the cutter tube 40 are retracted as the straw carriage 258 free wheels ( FIGS. 21-22 ).
[0093] Alternately, sliding pin spring 272 may be replaced with a ball detent mechanism (not shown) located on frame 204 that would engage with a small depression in proximal straw carriage 258 . This alternate mechanism in conjunction with biasing spring 256 would cause both the distal cutter carriage 250 and proximal straw carriage 258 to retract simultaneously from their fully distal position and to advance sequentially from their fully proximal position (i.e., cutter carriage 250 would fully advance and then the straw carriage 258 would advance).
[0094] At the end of the proximal movement of the cutter tube 40 , vacuum valve actuator 68 is moved proximally such that the distal and proximal dynamic O-ring seals 74 , 75 bracket the proximal port 80 and center port 82 of the distally open cylindrical valve bore 76 . Thereby, the interfacing vacuum conduit 16 draws air through the proximal vacuum conduit 90 , through the valve body 78 , through the distal vacuum conduit 86 , and ultimately from the vacuum lumen 32 ( FIG. 24 ). In FIG. 23 , this suction draws tissue 280 into the side aperture 34 of the probe assembly 28 .
[0095] It should be appreciated that in the illustrative version, the distal cutter carriage 250 does not freewheel ( FIG. 21 ) in its proximal-most position. Instead, rotation of the motor is stopped as the distal cutter carriage 250 is about to contact the proximal straw carriage 258 with closed-loop control based on an encoder (not shown) coupled to the DC motor 172 enabling accurate positioning of the motor output shaft 174 . Alternatively, freewheeling may be incorporated at the proximal-most position of the distal cutter carriage 250 by adding a section of no helical threads to the proximal end of the lead (translation) screw 244 equal to the longitudinal thickness of the distal cutter carriage 250 .
[0096] It should further be appreciated that free wheeling may be provided for cutter translation even without stacking straw sample retraction to avoid reliance upon other structures to block further translation or more elaborate closed loop position control.
[0097] The forward motor rotation key 162 is depressed to advance the cutter tube 40 , rotating lead (translation) screw 244 and rotation spur gear 246 , as depicted in FIG. 25 . Due to sliding pin spring 272 between carriages 250 , 258 , only the distal cutter carriage 250 engages with the lead screw threads 248 of the lead (translation) screw 244 and translates distally initially cutting tissue 280 , as depicted in FIG. 26 . Once the distal cutter carriage 250 approaches its distal-most position, the sliding pin 260 pulls the proximal straw carriage 258 into engagement with the lead screw threads 248 of the lead (translation) screw 244 . As the cutter carriage 250 freewheels, the elongate straw 102 is distally translated to encompass a first severed tissue sample 280 a , displacing proximally the indicator tube 150 a corresponding amount.
[0098] At this point, depression of the reverse motor rotation key 164 causes retraction of the proximal straw carriage 258 ( FIG. 18 ) with the side aperture 134 communicating with atmospheric pressure ( FIG. 17 ) as previously discussed so that the first severed tissue sample 280 a remains within the elongate straw 280 a . It should be appreciated that repeating the retraction and advancement of the cutter carriage 250 thereafter results in a second severed tissue sample 280 b being encompassed by the elongate straw 102 and the indicator tube 150 being further proximally displaced thereby as depicted in FIG. 27 . An additional retention feature is depicted in FIG. 27 wherein small bent-up, proximally directed tabs 284 formed in the elongate straw 102 resist distal movement of the severed tissue samples 280 a , 280 b . This automated sequencing of the cutter and straw carriages 250 , 258 during retraction and advancement may be repeated a number of times to take a plurality of samples without withdrawing the probe assembly 28 from tissue 280 . The surfaces of the elongate straw 102 may be coated with lubricous materials to aid in proximal movement of tissue through the elongate straw 102 and to reduce friction between the elongate straw 102 and the cutter tube 40 . Likewise, to aid in proximal movement of tissue through the elongate straw 102 , the diameter of the elongate straw 102 and the cutter tube 40 may be increased slightly some distance proximal from their distal end to reduce the friction of the tissue through the elongate straw 102 .
[0099] In FIG. 28 , a proximal end of the stacking straw assembly 100 includes a one-way latch (mechanical diode) 290 that engages the stacked cone shaped outer surface 152 of the indicator tube 150 as it proximally extends out of the elongate straw 102 preventing its being pneumatically drawn back into the elongate straw 102 when subsequently exposed to vacuum pressure.
[0100] In FIGS. 29, 30 , the proximal straw carriage 258 is shown to include distal and proximal J-hooks 300 , 302 that encompass on three sides the stacking straw assembly 100 . In particular, the rectangular recess 134 formed in the locking strip 118 is sized to longitudinally bracket the J-hooks 300 , 302 with the distal locking finger 136 preventing retraction as depicted in FIG. 29 when the triangular grips 114 , 116 are positioned horizontally ( FIG. 31 ), as would be typical before and during use of the biopsy device 10 . The surgeon may wish to segregate samples as they are taken or to take more samples than possible within one stacking straw assembly 100 . Extraction and replacement of the stacking straw assembly 100 is allowed by rotating the triangular grips one quarter turn counterclockwise (as viewed proximally) as depicted in FIG. 32 , which rotates the locking finger 136 out of alignment with the J-hooks 300 , 302 of the straw carriage 258 ( FIG. 30 ). A new stacking straw assembly 100 is then reinserted in reverse fashion.
[0101] In FIG. 33 , samples contained in the removed stacking straw assembly 100 may be accessed by pulling apart the triangular grips 114 , 116 causing the grooves 104 to peel apart the first and second straw halves 106 , 108 , which need not be symmetric. The samples may be removed individually or the samples and the straw half 106 portion of the straw 102 in which they are located may be put directly into a formalin solution for pathological preparation. Alternately, the samples contained in the stacking straw assembly 100 can be removed from the elongate straw 102 with a simple plunger-like rod (not shown) eliminating the need to peel apart the straw to access the tissue samples.
[0102] Although the integral vacuum assistance supported by a medical vacuum pump may often be advantageous, some surgeons may desire to palpitate tissue into a side aperture of a probe assembly without the assistance of vacuum. To that end, in FIGS. 34-36 , an alternative disposable probe 414 is depicted that omits a vacuum valve capability that responds to the cutter position but is otherwise identical to the afore-described disposable probe 14 . The modified components of the disposable probe assembly 414 include a substantially rectangular cover 422 sized to close the access trough recess 18 of the reusable hand piece 12 (not shown in FIGS. 34-36 ). The probe union sleeve 26 , attached to the inner surface 27 of the substantially rectangular cover 422 , communicates through a short pneumatic conduit 425 that terminates on the outer surface 79 at a hose nib 427 . Hose nib 427 may include an air and/or saline filter. Alternatively, hose nib 427 may be connected to a positive pressure source (e.g. fluid pump) or a negative pressure source (e.g., vacuum pump, syringe) to aspirate fluids. Hose nib 427 could also be used to lavage the tissue cavity with saline, pain medication, or bleeding control fluids. A core biopsy needle (“probe”) assembly 428 that passes longitudinally through the probe union sleeve 26 differs in that a cutter gear 444 needs only engage and respond to the distal cutter carriage 250 (not shown in FIGS. 34-36 ) and not also position a pneumatic valve. Cutter guide tab 445 extends out from the inner surface 27 to provide a distal stop for cutter gear 444 . Prior to insertion of the disposable probe 414 into the reusable hand piece 12 (not shown in FIGS. 34-36 ), the bayonet locking member 430 prevents axial movement of the stacking straw assembly 100 . The cutter gear 444 and cutter tube 40 cannot move proximally due to contact with the stacking straw assembly 100 and cannot move distally due to contact with the cutter guide tab 445 . By securing both the cutter and straw in a fully distal axial position, it insures that when the disposable probe 414 is inserted into the reusable hand piece 12 that the cutter gear 444 and stacking straw assembly 100 align and engage with the correct components within the reusable hand piece 12 .
[0103] In FIG. 37 , an alternative disposable assembly 514 is, as described in FIG. 3 but with the stacking straw assembly 100 , replaced with a straw assembly 516 having distal tube 518 attached to a proximally attached luer fitting 520 . The straw assembly 516 may be used to flush the cavity (via side aperture 34 ) with saline, epinephrine (or similar substances that reduce bleeding), or lidocane (or similar substances that reduce pain) by attaching a syringe or similar device (not shown) to the luer fitting 520 . To remove the saline, epinephrine, or lidocane from the tissue, the cutter tube 40 may be fully or partially retracted to insure that the valve assist valve assembly 52 is positioned to connect the lateral lumen (distal vacuum conduit 86 ) with the vacuum source ( and not simply atmospheric pressure) as depicted in FIG. 24 . The fluid would then be drawn from the tissue cavity (via side aperture 34 ), through the lateral lumen (distal vacuum conduit 86 ) and into a canister located in line with the vacuum source (not shown).
[0104] In FIG. 38 , an alternative biopsy needle (probe) assembly 628 is identical to that depicted in FIG. 14 with the exception of a probe tube 630 with through holes 631 placed proximate to the side aperture 34 . The vacuum lumen 32 thus communicates with the holes 631 in the probe tube 630 as an alternate means to apply saline, epinephrine, or lidocane to the tissue cavity. These through holes 631 allow the fluid to reach the cavity while the elongate straw 102 and indicator tube 150 remain distally positioned in the cutter tube 40 (i.e., during the middle of a biopsy sampling procedure). In this case, the syringe would be attached to the hose nib 88 via a stopcock fitting (not shown). With the stopcock valve positioned to connect the syringe directly to the needle's lateral lumen (distal vacuum conduit 86 ), when the syringe is depressed the fluid will enter the lateral lumen (distal vacuum conduit 86 ) and then flow into the tissue through the through holes 631 in the wall of the probe tube 630 . The cutter tube 40 would be positioned distally (side aperture 34 closed) while the fluid is being inserted into the cavity to prevent the tissue indicator tube 150 from being moved proximally due to the fluid pressure. During subsequent sampling cycles, the fluid would then be aspirated from the tissue cavity.
[0105] In FIGS. 39-45 , an alternative proximal stacking disposable assembly 702 is depicted that may also be used with the reusable hand piece 12 . Pneumatic force is employed to retrieve tissue samples rather than a mechanical movement from the reusable hand piece 12 that actuates a straw assembly. To that end, in FIG. 39 , a core biopsy needle (“probe”) assembly 704 is formed by a probe tube 706 with a distally positioned side aperture 708 . A cutter tube 710 is sized to closely fit and translate within an inner diameter (i.e., cutter lumen) 712 of the probe tube 706 with a length sufficient to close the side aperture 708 . The probe assembly 704 includes an underlying vacuum lumen 714 that communicates with the cutter lumen 712 via through holes 716 underlying the side aperture 708 . Both the probe tube 706 and vacuum lumen 714 distally terminate in open ends that communicate with each other via a curved manifold 718 defined inside of a piercing tip 720 that is attached as a distal-most portion of the probe assembly 704 . A distal tissue stop 722 projects from the piercing tip 720 into the distal open end of the probe tube 706 to maintain prolapsed tissue inside a sampling bowl 724 under the side aperture 708 within the cutter lumen 712 . Prolapsing occurs under the urging of axial vacuum force through the cutter lumen 712 and lateral vacuum force through the vacuum lumen 714 converging at the side aperture 708 . After distal translation of the rotated cutter tube 712 , a tissue sample 726 resides within a distal portion of the cutter tube 712 , wherein an inner diameter of the cutter tube 712 defines a tissue sample lumen 728 for guiding retrieval of samples 726 . Rather than subsequently distally advancing a straw to encompass and retract the tissue sample 726 , axial vacuum pressure as depicted by arrow 730 is asserted against a proximal face of the tissue sample 726 through the tissue sample lumen 728 with the cooperation of lateral pneumatic pressure as depicted by arrow 732 through vacuum lumen 14 and curved manifold 718 to a distal face of the tissue sample 726 .
[0106] In FIGS. 40-45 , the portions of the alternative proximal stacking disposable assembly 702 capture these tissue samples 726 . A proximal end of the cutter tube 710 extends through a probe union sleeve 734 to attach to a cutter gear 736 . A proximal end of the vacuum lumen 714 terminates within the probe union sleeve 734 . The alternative proximal stacking disposable assembly 702 includes a substantially rectangular cover 738 sized to close the access trough recess 18 ( FIGS. 2, 4 ), and omits pneumatic valve features. Instead, the distally positioned probe union sleeve 734 attached to an inner surface 740 of the substantially rectangular cover 738 communicates to a distal hose nib 742 formed on an outer surface 744 of the rectangular cover 738 and to the vacuum lumen 714 . A hose 746 is attached to the distal hose nib 742 to selectively provide pneumatic vacuum, pneumatic pressure, or fluid transfer (not shown). The alternate proximal stacking assembly 702 could likewise have a vacuum assist valve assembly 052 as depicted in FIG. 2 to selectively provide pneumatic vacuum, pneumatic pressure, or fluid transfer to the vacuum lumen 714 .
[0107] With particular reference to FIGS. 40, 42 , a rear tube 748 is aligned proximally to the cutter tube 710 and coupled for longitudinal movement thereto, although the rear tube 748 is disengaged from the rotational movement of the cutter tube 710 . This coupled movement may be achieved by an actuator that engages the distal cutter carriage 250 ( FIG. 4 ) or by a circular lip and groove engagement between the cutter tube 710 and rear tube 748 . The inner surface 740 of the rectangular cover 738 includes four support surfaces. First, a cutter guide 750 supports the cutter tube 710 proximal to the probe union sleeve 734 and distal to a most distal position of the cutter gear 736 . A distal rear tube guide 752 , is proximal to the most proximal position of the cutter gear 736 , and a proximal rear tube guide 754 , and distal to a most distal position of a proximal locking flange 756 of the rear tube 748 , to maintain alignment of the rear tube 748 . A bottom half-cylinder locking flange 758 at a proximal end of the rectangular cover 738 cooperates with the proximal locking flange 756 of the rear tube 748 to lock to a sample holding portion 760 of the alternative proximal stacking disposable assembly 702 . The sample holding portion 760 extends proximal to the rectangular cover 738 and the reusable hand piece 712 and thus may be readily replaced during a biopsy procedure.
[0108] A distal locking half cylindrical portion 762 engages the bottom half-cylinder locking flange 758 . The distal locking half cylindrical portion 762 is attached to a proximal half cylindrical portion 764 to form an outer sleeve 766 . A reciprocating member 768 , which engages the proximal locking flange 756 of the rear tube 748 and is partially encompassed by the outer sleeve 766 , engages and distally advances a more proximal rod 770 out of an external vacuum lumen 772 defined as an inner diameter of an external vacuum tube 773 . The rod has a down turned distal end 774 that exits an opening 776 in the proximal half cylindrical portion 764 . A flexible, peel-apart external tissue tube 777 defining an external tissue lumen 778 is formed from an inwardly open channel 780 closed by an elongate seal 782 .
[0109] Rod 770 may be formed of a fluoropolymer resin material such as TEFLON™ or other suitable flexible material having a low coefficient of friction. Rod 770 may be sized and shaped to conform closely to the inner diameter (i.e., vacuum lumen 772 ) of vacuum tube 773 . The close fit between rod 770 and vacuum lumen 773 , as well as the low friction properties of the rod 770 , enable the rod 770 to translate easily within the vacuum lumen 772 without any loss of vacuum force through the distal end of the vacuum lumen 772 . The inwardly open channel 780 may advantageously be formed of polyvinyl chloride or another similar type of flexible, water insoluble material so that stacked tissue samples may be visible. A proximal end of the open channel 780 is attached to and closed by a lumen peel tab 784 . A proximal end of the external vacuum lumen 772 is attached to a vacuum line 786 via a tubing connector 788 .
[0110] In FIGS. 40, 41 , the alternative proximal stacking disposable assembly 702 is in an initial condition with the rod 770 at its proximal most position in the external vacuum lumen 772 . The cutter gear 736 and thus the rear tube 748 , reciprocating member 768 and flexible, peel-apart external tissue lumen 778 are in their distal most position. In FIGS. 43, 44 , the rod 770 has extruded distally out of the opening 776 in the proximal half cylindrical portion 764 of the outer sleeve 766 , denoting reciprocating cycles to retract at least one tissue sample (not shown) that is held within a proximal portion of the external tissue lumen 778 . The cutter gear 736 and thus the rear tube 748 , reciprocating member 768 and flexible, peel-apart external tissue lumen 778 are in their proximal most positions relative to the outer sleeve 766 and rectangular cover 738 . The relative change causes the flexible, peel-apart external tissue lumen 778 to bow away from the outer sleeve 766 . In FIG. 45 , the lumen peel tab 784 has been pulled to separate the inwardly open channel 780 from the elongate seal 782 to reveal and possibly access stored tissue samples (not shown).
[0111] In FIGS. 46-48 , the sample holding portion 760 is depicted in greater detail. The distal locking half cylindrical portion 762 of the outer sleeve 766 includes upper lateral locking arms 790 that lock into the bottom half-cylinder locking flange 758 at the proximal end of the rectangular cover 738 . In FIGS. 46, 47 , aligned below these, lower lateral locking arms 792 of a distal interface portion 794 of the reciprocating member 768 lock into the proximal locking flange 756 of the rear tube 748 . The distal interface portion 794 of the reciprocating member 768 includes an axially-extending bore 796 for connecting the external tissue lumen 778 of the sample holding portion 760 to the rear tube 748 , maintaining generally coaxial alignment of the probe assembly 702 , tissue sample lumen 728 , rear tube 748 , bore 796 , and external tissue lumen 778 to provide an unobstructed passageway for the aspiration of tissue samples from the cutter tube 710 .
[0112] In FIGS. 48 , 50 - 51 , the flexible rod 770 may be advanced distally within the external vacuum lumen 772 by the interaction between side ratchet teeth 798 and a pawl-type latching mechanism 800 on the reciprocating member 768 , which is shown in greater detail in FIG. 49 . Reciprocating member 768 may be supported on lower lateral latch arms 792 and reciprocate as cutter tube 710 is advanced and retracted. Reciprocating member 768 may have a bifurcated proximal end with proximally extending portions 802 separated by an axially extending slot 804 . A ramped surface 806 is formed between portions 802 at a distal end of slot 804 . Ramped surface 806 may serve to deflect the distal end 774 of rod 770 through the opening 776 in the outer sleeve 766 as the rod 770 is ratcheted out of external vacuum lumen 772 . Unidirectional engagement pawls 808 formed to inwardly extend from the proximally extending portions 802 into the axially extending slot 804 engage side ratchet teeth 798 on rod 770 as the rod 770 extends through the axially extending slot 804 . The engagement between pawls 808 and side ratchet teeth 798 advances rod 770 distally through vacuum lumen 772 .
[0113] In FIG. 51 , a plurality of small holes 810 may be formed in a center wall divider 812 of the external vacuum tube 773 between external vacuum lumen 772 and tissue lumen 778 . Small holes 810 enable vacuum from a source (not shown) connected to vacuum line 786 to communicate from external vacuum lumen 772 into external tissue lumen 778 , to provide vacuum in tissue sample lumen 728 in cutter tube 710 . Small holes 810 may be spaced along the longitudinal axis of tube vacuum tube 773 and separated by a distance in the range of 0.1 to 4 centimeters. Holes 810 may be oriented at an angle relative to the longitudinal axis of vacuum tube 773 . The angle in holes 810 may function as a mechanical diode, in that the edge of the holes 810 opening into the tissue lumen 778 may aid in preventing motion of tissue samples 726 in a distal direction, while permitting tissue samples 726 to move proximally in tissue lumen 778 under vacuum force provided by the vacuum line 786 . A tissue sample 726 may continue to slide proximally through the tissue lumen 778 until the sample 726 contacts either a proximal tissue stop 812 attached to the lumen peel tab 784 or a preceding tissue sample 726 .
[0114] With further reference to FIG. 51 , small holes 810 may be formed between lumens 772 , 778 by boring top holes 813 into an upper surface 814 of external vacuum tube 773 with the sharpened tip of a drill or other appropriate instrument. The tip of the drill bit or other boring instrument may be directed to pass through vacuum lumen 772 to penetrate the center wall divider 812 that separates the two lumens 772 , 778 .The proximal half cylindrical portion 764 of the outer sleeve 766 may be securely attached to the upper surface 814 of the external vacuum tube 773 following the drilling of vacuum communication small holes 810 to seal top holes 813 . For instance, outer sleeve 766 may be attached to the external vacuum tube 773 by an adhesive or other appropriate type of attachment mechanism.
[0115] As tissue samples 726 are stored in tissue lumen 778 , the stack of samples 726 will grow in length distally in tissue lumen 778 . The samples 726 will tend to block or otherwise restrict flow communication through small holes 810 as the stack of samples 726 extends distally in tissue lumen 778 . The translating flexible rod 770 is shown disposed at least partially in vacuum lumen 772 . Rod 770 extends axially through vacuum lumen 772 to selectively cover or otherwise block at least some of the small holes 810 . Rod 770 may be manipulated, such as by axial movement of rod 770 , to selectively expose small holes 810 in the vacuum tube 773 in compensation for those holes 810 blocked by stacked tissue samples 726 . For instance, during each cutting cycle, rod 770 may be advanced distally within vacuum lumen 772 to expose or otherwise unblock/open additional small holes 810 as additional samples 726 are stored in tissue lumen 778 . The movement of rod 770 maintains a predetermined number of small holes 810 open to provide flow communication between vacuum and tissue lumens 772 and 778 as additional tissue samples 726 are added to the stack of tissue samples 726 in tissue lumen 778 , thereby facilitating a generally consistent vacuum force, depicted as arrow 816 , in tissue sample lumen 728 in the probe assembly 704 ( FIG. 39 ) throughout multiple cutting cycles.
[0116] Initially as depicted in FIG. 52 , flexible rod 770 may be inserted within vacuum lumen 772 such that rod 770 is axially offset within vacuum lumen 772 so as to cover or otherwise block most, but not all, of the small holes 810 . For instance, prior to storing any samples 726 in tissue lumen 778 , rod 770 may be offset distally within vacuum lumen 772 a distance that is slightly longer than the length of side aperture 708 ( FIG. 40 ). Offsetting rod 770 distally within the vacuum lumen 772 ensures an initial set of small holes 810 are exposed to communicate axial vacuum force 730 to side aperture 708 when cutter tube 710 is in the fully proximal position prior to tissue sampling. The axial vacuum force 730 communicated through the exposed small holes 810 aids in prolapsing tissue into side aperture 708 prior to cutting, as well as pulling the tissue sample 726 proximally into tissue lumen 778 after cutting. As a tissue sample 726 is drawn into and stacked within tissue lumen 778 , the tissue sample 726 blocks the previously exposed small holes 810 , preventing vacuum from passing into the tissue lumen 778 . Rod 770 may be selectively moved a predetermined distance distally that is slightly longer than the length of side aperture 708 to expose additional small holes 810 immediately distal of the most recently acquired tissue sample 726 . Rod 770 may be adapted to be automatically advanced distally by the translation of the cutter carriage 250 . The newly exposed small holes 810 continue the communication of vacuum force 816 into tissue lumen 778 for the next cutting cycle. As reciprocating member 768 retracts proximally, unidirectional bottom ratchet teeth 818 located on the bottom side of flexible rod 770 engage the small holes 810 within vacuum lumen 772 . The engagement between the bottom ratchet teeth 818 and small holes 810 prevents rod 770 from moving proximally within vacuum lumen 772 . As pawls 808 move proximally relative to rod 770 , the pawls 808 engage the next proximal set of side ratchet teeth 798 on rod 770 . This engagement with the next set of side ratchet teeth 798 causes rod 770 to again advance distally when the reciprocating member 768 advances distally during the next cutting cycle to expose additional small holes 810 . In the event that the cutter tube 710 , and thus the reciprocating member 768 , is advanced and retracted without the probe assembly 704 in tissue, the result is that the flexible rod 770 advances too far distally relative to the tissue samples 726 ; the flexible rod 770 may be rotated a fraction of a turn about its longitudinal axis to disengage side ratchet teeth 798 and pawls 808 allowing the flexible rod 770 to be repositioned proximally within the vacuum lumen 772 .
[0117] A similar sample holding portion is described in five commonly-owned and co-pending U.S. patent application Ser. No. 10/953834, “Biopsy Apparatus and Method” END-5469; Ser. No. 10/953,904 “Improved Biopsy Apparatus and Method” END 5470; Ser. No. 10/953,397 “Fluid Control for Biopsy Device” END 5471; Ser. No. 10/953,395 “Biopsy Device with Sample Storage” END 5472; and Ser. No. 10/953,389 “Cutter for Biopsy Device” END 5473, all to Hibner et al. and filed on 29 Sep. 2004, the disclosures of which are hereby incorporated by reference in their entirety.
[0118] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the spirit and scope of the appended claims. Additionally, each element described in relation to the invention may be alternatively described as a means for performing that element's function.
[0119] For example, one or more sensors may be incorporated into the hand piece 12 to sense the actual position of each carriage or to sense the particular disposable probe assembly assembled into the hand piece 12 . | A biopsy device and method are provided for obtaining a tissue sample, such as a breast tissue biopsy sample. The biopsy device includes a disposable probe assembly with an outer cannula having a distal piercing tip, a cutter lumen, and a cutter tube that rotates and translates past a side aperture in the outer cannula to sever a tissue sample. The biopsy device also includes a reusable hand piece with an integral motor and power source to make a convenient, untethered control for use with ultrasonic imaging. The reusable hand piece incorporates a probe oscillation mode to assist when inserting the distal piercing tip into tissue. A straw stacking assembly is automatically positioned by the reusable hand piece to retract multiple samples with a single probe insertion as well as giving a visual indication to the surgeon of the number of samples that have been taken. | 0 |
CROSS-REFERENCE TO RELATED APPLICATION
[0001] The instant application claims priority to U.S. Provisional Patent Application Ser. No. 61/387,076, filed Sep. 28, 2010, the entire specification of which is expressly incorporated herein by reference.
FIELD OF INVENTION
[0002] The present invention relates generally to scissor systems, and more particularly to scissor systems that improve the performance of curved, straight and hooked scissors, by adding a supporting secondary jaw member such that the characteristics of a typical scissor's skewing or failure to cut due to reduced sharpness or excessive bite are eliminated or at least reduced significantly.
BACKGROUND OF THE INVENTION
[0003] Endoscopy, and especially laparoscopic endoscopy, has been a rapidly growing surgical practice in the past few decades. The technology began, and is still managed, primarily with hand held instruments, the majority of which are instruments using monopolar RF energy sources to assist in coagulation, cauterizing and cutting of various types of tissue. The largest selling type of these instruments is scissors. Scissors of many designs have been designed and applied to endoscopic surgery, such as, but not limited to: (1) double jaw scissors, including straight and curved designs; (2) single jaw scissors, including straight and curved designs; (3) hook scissors, including single jaw and straight designs; and variants of the above.
[0004] Surgeons expect scissors to be sharp at all times and to cut for all or at least the majority of the jaws' length. Furthermore, surgeons expect perfect cutting action with both thick and thin tissue, soft and hard tissue, and/or slippery tissue. These expectations present serious challenges to the designers of surgical scissors. Unfortunately, conventional scissor systems, including those used for various surgical applications, do not provide the performance needed by surgeons, especially with respect to providing exceptional and consistent cutting action.
[0005] Accordingly, there exists a need for new and improved scissor systems that overcomes at least one of the above-described disadvantages.
SUMMARY OF THE INVENTION
[0006] In accordance with the general teachings of the present invention, new and improved scissor systems are provided. More specifically, the present invention provides new and improved scissor systems that may be used in various surgical applications. By way of a non-limiting example, the present invention provides scissor systems in various combinations wherein continuous cut and non-skewing characteristics are provided even when the scissor is not perfectly sharp and is compatible with a large variety of tissue types, e.g., thin, thick, hard, soft or even slippery. By way of another non-limiting example, these design parameters of the scissor systems of the present invention are achieved, at least in part, by adding to the scissor system's designs a secondary, lower parallel jaw member, thus supporting a stand alone blade or jaw member against the reinforced blade or jaw member continuously through the cutting action, while maintaining continuous interference, i.e., shear action, and sharply reducing the probability of skewing or spreading.
[0007] In accordance with one embodiment of the present invention, a scissor system is provided, comprising: a first jaw member having a cutting surface formed thereon; a second jaw member having a cutting surface formed thereon; and a beam member positioned substantially parallel to the cutting surface of the second jaw member.
[0008] In accordance with an aspect of this embodiment, the first and second jaw members are pivotally engaged to each other so as to be selectively operable to open apart from each other and close together towards each other to selectively perform a cutting action.
[0009] In accordance with an aspect of this embodiment, the beam member maintains engagement of the cutting surfaces of the first and second jaw members through substantially the entirety of the cutting action.
[0010] In accordance with an aspect of this embodiment, the beam member supports the first jaw member so as to substantially prevent the first jaw member from being pushed away from the second jaw member during the cutting action.
[0011] In accordance with an aspect of this embodiment, either the first or second jaw members include a curved portion.
[0012] In accordance with an aspect of this embodiment, the curved portions of the first and second jaw members are not identical.
[0013] In accordance with an aspect of this embodiment, the first jaw member includes a hook member formed on a distal portion thereof.
[0014] In accordance with an aspect of this embodiment, the second jaw member includes a pair of spaced and opposed hook members formed on a distal portion thereof.
[0015] In accordance with an aspect of this embodiment, the second jaw member and the beam member define a cavity formed therebetween.
[0016] In accordance with an aspect of this embodiment, the first jaw member is selectively operable to be at least partially received within the cavity.
[0017] In accordance with a first alternative embodiment of the present invention, a scissor system is provided, comprising: a first jaw member having a cutting surface formed thereon; a second jaw member having a cutting surface formed thereon; and a beam member positioned substantially parallel to the cutting surface of the second jaw member; wherein the first and second jaw members are pivotally engaged to each other so as to be selectively operable to open apart from each other and close together towards each other to selectively perform a cutting action; wherein the beam member maintains engagement of the cutting surfaces of the first and second jaw members through substantially the entirety of the cutting action.
[0018] In accordance with an aspect of this embodiment, the beam member supports the first jaw member so as to substantially prevent the first jaw member from being pushed away from the second jaw member during the cutting action.
[0019] In accordance with an aspect of this embodiment, either the first or second jaw members include a curved portion.
[0020] In accordance with an aspect of this embodiment, the curved portions of the first and second jaw members are not identical.
[0021] In accordance with an aspect of this embodiment, the first jaw member includes a hook member formed on a distal portion thereof.
[0022] In accordance with an aspect of this embodiment, the second jaw member includes a pair of spaced and opposed hook members formed on a distal portion thereof.
[0023] In accordance with an aspect of this embodiment, the second jaw member and the beam member define a cavity formed therebetween.
[0024] In accordance with an aspect of this embodiment, the first jaw member is selectively operable to be at least partially received within the cavity.
[0025] In accordance with a second alternative embodiment of the present invention, a scissor system is provided, comprising: a first jaw member having a cutting surface formed thereon; a second jaw member having a cutting surface formed thereon; and a beam member positioned substantially parallel to the cutting surface of the second jaw member; wherein the first and second jaw members are pivotally engaged to each other so as to be selectively operable to open apart from each other and close together towards each other to selectively perform a cutting action; wherein the beam member maintains engagement of the cutting surfaces of the first and second jaw members through substantially the entirety of the cutting action; wherein the beam member supports the first jaw member so as to substantially prevent the first jaw member from being pushed away from the second jaw member during the cutting action.
[0026] In accordance with an aspect of this embodiment, either the first or second jaw members include a curved portion.
[0027] In accordance with an aspect of this embodiment, the curved portions of the first and second jaw members are not identical.
[0028] In accordance with an aspect of this embodiment, the first jaw member includes a hook member formed on a distal portion thereof.
[0029] In accordance with an aspect of this embodiment, the second jaw member includes a pair of spaced and opposed hook members formed on a distal portion thereof.
[0030] In accordance with an aspect of this embodiment, the second jaw member and the beam member define a cavity formed therebetween.
[0031] In accordance with an aspect of this embodiment, the first jaw member is selectively operable to be at least partially received within the cavity.
[0032] 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 purposed of illustration only and are not intended to limit the scope of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0033] Other advantages of the present invention will be readily appreciated as the same becomes better understood by reference to the following detailed description when considered in connection with the accompanying drawings wherein:
[0034] FIG. 1 illustrates a perspective view of a surgical instrument including a scissor system, in accordance with a first embodiment of the present invention;
[0035] FIG. 2 illustrates a top perspective view of the scissor system depicted in FIG. 1 , in accordance with a first embodiment of the present invention;
[0036] FIG. 3 illustrates a bottom perspective view of the scissor system depicted in FIG. 1 , in accordance with a first embodiment of the present invention;
[0037] FIG. 4 illustrates a second top perspective view of the scissor system depicted in FIG. 1 , in accordance with a first embodiment of the present invention;
[0038] FIG. 5 illustrates a third top perspective view of the scissor system depicted in FIG. 1 , in accordance with a first embodiment of the present invention;
[0039] FIG. 6 illustrates a top perspective view of the lower jaw member of the scissor system depicted in FIG. 1 , in accordance with a first embodiment of the present invention;
[0040] FIG. 7 illustrates a second top perspective view of the lower jaw member of the scissor system depicted in FIG. 1 , in accordance with a first embodiment of the present invention;
[0041] FIG. 8 illustrates a side view of the upper jaw member of the scissor system depicted in FIG. 1 , in accordance with a first embodiment of the present invention;
[0042] FIG. 9 illustrates an end view of the scissor system depicted in FIG. 1 , in accordance with a first embodiment of the present invention;
[0043] FIG. 10 illustrates a perspective view of the activating shaft member inside the hollow tube member of the surgical instrument depicted in FIG. 1 , in accordance with a first embodiment of the present invention;
[0044] FIG. 11 illustrates a second perspective view of the activating shaft member of the surgical instrument depicted in FIG. 1 , in accordance with a first embodiment of the present invention;
[0045] FIG. 12 illustrates a perspective view of the hollow tube member of the surgical instrument depicted in FIG. 1 , in accordance with a first embodiment of the present invention;
[0046] FIG. 13 illustrates a perspective view of the isolative material of the surgical instrument depicted in FIG. 1 , in accordance with a first embodiment of the present invention;
[0047] FIG. 14 illustrates a perspective view of a first alternative scissor system, in accordance with a second embodiment of the present invention;
[0048] FIG. 15 illustrates a second perspective view of the scissor system depicted in FIG. 14 , in accordance with a second embodiment of the present invention;
[0049] FIG. 16 illustrates a top perspective view of the scissor system depicted in FIG. 14 , in accordance with a second embodiment of the present invention;
[0050] FIG. 17 illustrates a perspective view of a second alternative scissor system, in accordance with a third embodiment of the present invention;
[0051] FIG. 18 illustrates a perspective view of a lower jaw member of the scissor system depicted in FIG. 17 , in accordance with a third embodiment of the present invention;
[0052] FIG. 19 illustrates a perspective view of an upper jaw member of the scissor system depicted in FIG. 17 , in accordance with a third embodiment of the present invention;
[0053] FIG. 20 illustrates a perspective view of a third alternative scissor system, in accordance with a fourth embodiment of the present invention;
[0054] FIG. 21 illustrates a perspective view of an upper jaw member of the scissor system depicted in FIG. 20 , in accordance with a fourth embodiment of the present invention;
[0055] FIG. 22 illustrates a perspective view of a lower jaw member of the scissor system depicted in FIG. 20 , in accordance with a fourth embodiment of the present invention;
[0056] FIG. 23 illustrates a perspective view of a fourth alternative scissor system, in accordance with a fifth embodiment of the present invention;
[0057] FIG. 24 illustrates a perspective view of a fifth alternative scissor system, in accordance with a sixth embodiment of the present invention;
[0058] FIG. 25 illustrates a perspective view of a sixth alternative scissor system, in accordance with a seventh embodiment of the present invention;
[0059] FIG. 26 illustrates a perspective view of the scissor system depicted in FIG. 25 with the hollow tube member removed for purposes of illustration, in accordance with a seventh embodiment of the present invention;
[0060] FIG. 27 illustrates a perspective view of the hollow tube member of the scissor system depicted in FIG. 25 with the jaw members removed for purposes of illustration, in accordance with a seventh embodiment of the present invention;
[0061] FIG. 28 illustrates a perspective view of the lower jaw member of the scissor system depicted in FIG. 25 , in accordance with a seventh embodiment of the present invention;
[0062] FIG. 29 illustrates a second perspective view of the lower jaw member of the scissor system depicted in FIG. 25 , in accordance with a seventh embodiment of the present invention;
[0063] FIG. 30 illustrates a perspective view of the upper jaw member of the scissor system depicted in FIG. 25 , in accordance with a seventh embodiment of the present invention;
[0064] FIG. 31 illustrates a perspective view of a seventh alternative scissor system, in accordance with an eighth embodiment of the present invention;
[0065] FIG. 32 illustrates a perspective view of the upper jaw member of the scissor system depicted in FIG. 31 with the hollow tube member being shown in phantom for purposes of illustration, in accordance with an eighth embodiment of the present invention;
[0066] FIG. 33 illustrates a perspective view of the lower jaw member of the scissor system depicted in FIG. 31 , in accordance with an eighth embodiment of the present invention;
[0067] FIG. 34 illustrates a perspective view of the upper jaw member of the scissor system depicted in FIG. 31 , in accordance with an eighth embodiment of the present invention;
[0068] FIG. 35 illustrates a perspective view of the lower jaw member of the scissor system depicted in FIG. 31 with a portion of the hollow tube member removed for purposes of illustration, in accordance with an eighth embodiment of the present invention; and
[0069] FIG. 36 illustrates a second perspective view of the lower jaw member of the scissor system depicted in FIG. 31 , in accordance with an eighth embodiment of the present invention.
[0070] The same reference numerals refer to the same parts throughout the various Figures.
DETAILED DESCRIPTION OF THE INVENTION
[0071] The following description of the preferred embodiment(s) is merely exemplary in nature and is in no way intended to limit the invention, or uses.
[0072] Referring to the Figures generally, and specifically to FIG. 1 , there is shown an illustrative endoscopic forceps system generally at 10 . It should be appreciated, however, that the scissor systems of the present invention may be used with any type of cutting instrument or system and is not limited in any way to only surgical instruments or systems.
[0073] The system 10 , primarily includes, at a proximal portion thereof, a pair of handle members 20 and 30 , respectively, wherein handle member 20 is free to pivot (e.g., via a pivot point 22 ) on or about handle member 30 . When handle member 20 is caused to pivot on or about handle member 30 , e.g., by the action of the surgeon, a reciprocating action (e.g., in a back-and-forth or to-and-fro motion) is effected on an activating shaft member 40 that may be at least partially disposed within a hollow tube member 50 . This reciprocating action caused by the opening and/or closing of handle members 20 and 30 ultimately results in the opening apart and/or closing together of blade or jaw members 60 and 70 , respectively, of the scissor system 80 , which is disposed at a distal portion of the system 10 . It is this opening apart and/or closing together of blade or jaw members 60 and 70 that provide the cutting action of the scissor system 80 .
[0074] Referring to FIGS. 2-13 , there is shown various additional views of the system 10 depicted in FIG. 1 . For purposes of reference, the single blade or jaw member 60 is referred herein as the “upper” jaw member and the reinforced blade or jaw member 70 is referred herein as the “lower” jaw member. However, it should be appreciated that these terms are being used for reference purposes only and are not meant to limit the scope of the present invention. Likewise, it should be appreciated that terms such as “top” or “bottom” are also being used for reference purposes only and are not meant to limit the scope of the present invention. Furthermore, for purposes of brevity, the phrase “jaw member, as used herein,” will be understood to also optionally include at least one cutting surface formed thereon.
[0075] The jaw members 60 and 70 may be jointly held within a clevis member 90 or other suitable device and may be generally free to rotate on or about a common pin member 100 or other suitable device. Additionally, an isolative material 110 (i.e., heat shrink) may be placed over the tube member 50 so as to avoid undesired arcing between the tube member 50 and any adjacent tissue (e.g., when the system 10 is used in conjunction with electrically powered use during a surgical procedure).
[0076] By way of a non-limiting example, as the upper jaw member 60 is rotating towards the lower jaw member 70 , an attached secondary beam member 72 maintains the engagement of the cutting edges 60 a and 70 a of jaw members 60 and 70 , respectively, through the entirely or substantially through the entirety of the cutting action and help support the upper jaw member 60 against being pushed apart off of the lower jaw member 70 or skewing therefrom, thus resulting in a failure to cut or a poor quality cut.
[0077] By way of a non-limiting example, the secondary beam member 72 may be parallel to the lower jaw member 70 at a distance that is equal to the thickness of the upper jaw member 60 plus a small tolerance factor (e.g., preferably below 0.002 inches or 0.05 mm).
[0078] The curvature of the upper jaw member 60 preferably protrudes the curvature of the lower jaw member 70 so that the cutting point propagates from a contact point 120 to the distal end thereof upon closure of the jaw members 60 and 70 , respectively. That is, the curvature of the upper jaw member 60 is not identical to the curvature of the lower jaw member 70 . By way of a non-limiting example, upper jaw member 60 should conform to the space between the lower jaw member 70 and secondary beam member 72 by elastic deflection.
[0079] By way of a non-limiting example, both jaw members 60 and 70 may pivot on the common pin member 100 that may be positioned in an area defining a hole 140 . Cams 150 , being activated by a common pin member 160 , may be held in by a clevis member 170 at the distal end of the activating shaft member 40 .
[0080] Referring to FIGS. 14-16 , there is shown another embodiment of the scissor systems of the present invention. In these views, the scissor system 200 is provided with a least one, and more preferably, a plurality of hook members 210 , 220 , 222 , respectively, located at the distal portions of the jaw members 230 , 240 , respectively. It should also be appreciated that the jaw members 230 , 240 , respectively, can be “hookless” as well, include only one hook member each, and/or two hook members each, or any combination thereof. By way of a non-limiting example, this is feature is particularly advantageous when attempting to anchor slippery tissue during a surgical procedure. As previously noted, the jaw members 230 , 240 , respectively, may include cutting edges formed on a surface thereof.
[0081] Referring to FIGS. 17-19 , there is shown another alternative embodiment wherein the scissor system 300 is shown with a single hook member 310 located on the “top” or “upper” jaw member 320 , whereas the “lower” or “bottom” jaw member 330 does not include a hook member. Again, it should also be appreciated that the jaw members 320 , 330 , respectively, can be “hookless” as well, include only one hook member each, and/or two hook members each, or any combination thereof. As previously noted, the jaw members 320 , 330 , respectively, may include cutting edges formed on a surface thereof.
[0082] Referring to FIGS. 20-22 , there is shown still another alternative embodiment wherein the scissor system 400 does not includes any curved jaw members, but rather includes two substantially straight jaw members 410 , 420 , respectively. In this view, a single hook member 430 is located on the “top” or “upper” jaw member 410 , whereas the “lower” or “bottom” jaw member 420 does not include a hook member. Again, it should also be appreciated that the jaw members 410 , 420 , respectively, can be “hookless” as well, include only one hook member each, and/or two hook members each, or any combination thereof. As previously noted, the jaw members 410 , 420 , respectively, may include cutting edges formed on a surface thereof.
[0083] Referring to FIG. 23 , there is shown a further alternative embodiment, wherein a general purpose, curved scissor system 500 is provided, wherein the scissor system 500 is shown with a single hook member 510 located on the “top” or “upper” jaw member 520 , whereas the “lower” or “bottom” jaw member 530 does not include a hook member. Again, it should also be appreciated that the jaw members 520 , 530 , respectively, can be “hookless” as well, include only one hook member each, and/or two hook members each, or any combination thereof. As previously noted, the jaw members 520 , 530 , respectively, may include cutting edges formed on a surface thereof.
[0084] The jaw members 520 , 530 , respectively, may be provided with handle members 520 a , 530 a , respectively, that may pivot relative to one another at a pivot point 505 . In this view, the jaw members 520 , 530 , respectively, may be directly joined to, or integrally formed with, the handle members 520 a , 530 a , respectively.
[0085] Referring to FIG. 24 , there is shown still a further embodiment, wherein a general purpose, substantially straight scissor system 600 is provided, wherein the scissor system 600 is shown with a single hook member 610 located on the “top” or “upper” jaw member 620 , whereas the “lower” or “bottom” jaw member 630 does not include a hook member. Again, it should also be appreciated that the jaw members 620 , 630 , respectively, can be “hookless” as well, include only one hook member each, and/or two hook members each, or any combination thereof. As previously noted, the jaw members 620 , 630 , respectively, may include cutting edges formed on a surface thereof.
[0086] The jaw members 620 , 630 , respectively, may be provided with handle members 620 a , 630 a , respectively, that may pivot relative to one another at a pivot point 605 . In this view, the jaw members 620 , 630 , respectively, may be directly joined to, or integrally formed with, the handle members 620 a , 630 a , respectively.
[0087] Referring to FIGS. 25-30 , there is shown still yet another further embodiment, wherein a scissor system 700 is provided. The system 700 may be activated (i.e., in a cutting action) by one or more link members 710 , 720 , respectively, that may be pivotally attached to a distal end of an activating shaft member 730 via holed or keyed male ends or protuberances 740 , 750 , respectively, (see areas defining holes at 740 a , 750 a , respectively), formed on the proximal portions of the jaw members, 760 , 770 , respectively. As previously noted, the jaw members 760 , 770 , respectively, may include cutting edges formed on a surface thereof.
[0088] The jaw members, 760 , 770 , respectively, can be joined to the distal end of the activating shaft member 730 via a common pin member 780 (e.g., aligned through an area defining one or more holes 790 , 792 , respectively formed in the distal portion of the activating shaft member 730 , and an area defining a hole 794 , 796 , respectively, formed on the jaw members, 760 , 770 , respectively), such that, as the activating shaft member 730 moves in a back-and-forth or to-and-fro motion (due to the actuation of the handle members (not shown)), the jaw members, 760 , 770 , respectively, will open or close, as the case may be, and in doing so, will be selectively operable to perform a cutting action.
[0089] Referring to FIGS. 31-36 , there is shown still yet another further alternative embodiment, wherein a scissor system 800 is provided. The system 800 includes a substantially straight movable “top” or “upper” jaw member 810 and a “static” or “fixed,” “bottom” or “lower” jaw member 820 . As previously noted, the jaw members 810 , 820 , respectively, may include cutting edges formed on a surface thereof.
[0090] It should also be appreciated that one or more curved jaw members may also be used in conjunction with this embodiment as well.
[0091] The lower jaw member 820 may be preferably integrally formed with the distal end of a tube member 830 or may be joined thereto in any number of suitable manners (e.g., adhesively joined, welded, and/or the like). An activating shaft member 730 may reciprocate within the tube member 830 and thus activate jaw member 810 via a pin member 840 sliding within a cam 850 formed in jaw member 810 . Jaw member 810 may pivot on or about the jaw member 820 via common pin member 860 (e.g., similar to the arrangement described in connection with FIGS. 24-29 ) disposed within an area defining a hole 870 formed in jaw member 810 .
[0092] The variants shown herein are for illustrative purposes only. It should be appreciated that features such as but not limited to hooks, cross supports between jaws and secondary beams, curvature changes, and additional features to the blades, such as but not limited to rasped edges, scallops, and/or the like, may be added to the scissor systems of the present invention.
[0093] Furthermore, although the above description pertains primarily to endoscopic scissor systems, it should be appreciated that the present invention is applicable as well to open surgery scissors, industrial scissors such as those used by barbers, tailors, and other craftsmen, as well as large scissors-like applications such as logging and shearing of substances with two blades.
[0094] While the invention has been described with reference to an exemplary embodiment, it will be understood by those skilled in the art that various changes can be made and equivalents can be substituted for elements thereof without departing from the scope of the invention. In addition, many modifications can be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention, but that the invention will include all embodiments falling within the scope of the appended claims. | Scissor systems are described. The scissor systems are provided with a secondary, lower parallel jaw member that supports a stand alone blade or jaw member against a reinforced blade or jaw member continuously through the cutting action, while simultaneously maintaining continuous interference, i.e., shear action, and sharply reducing the probability of skewing or spreading. | 0 |
This application is a National Stage application of PCT/FR2005/000011, filed Jan. 5, 2005, which claims priority from French patent application FR 0400044, filed Jan. 6, 2004. The entire contents of each of the aforementioned applications are incorporated herein by reference.
GENERAL AREA OF THE INVENTION
The invention concerns a method and a device for partially crystallising a solution in a continuous stream or a semi-continuous stream such as a fluctuating stream for example.
STATE OF THE ART
In certain applications, it is desired to be able to partially crystallise a dissolved phase of a solution in circulation in a device.
The freezing of a solution is achieved by lowering its temperature. The start-of-freezing temperature is the temperature at which the first ice crystals are able to appear.
However, in practice it is necessary to lower the temperature below the start-of-freezing temperature in order to bring about the start of crystallisation. This phenomenon is called supercooling. The phenomenon of the appearance of the first crystals is called “supercooling rupture” and the difference between the start-of-freezing temperature and the temperature at which crystallisation will start is called the “supercooling amplitude”.
The appearance of the first crystals is called “nucleation” and is an exothermic phenomenon that gives off heat. The temperature of the mixture composed of the solution and the ice crystals will therefore rise to a temperature slightly below the start-of-freezing temperature during supercooling rupture. By continuing to cool the mixture, we encourage the growth of the crystals formed during supercooling rupture, and also trigger the appearance of new crystals. This last phenomenon is called secondary crystallisation.
The mass concentration of ice crystals related to the unit of mass of the solution is called the ice grade.
The partial freezing or partial crystallisation of a solution therefore aims, starting from a solution of zero ice density grade and whose temperature is in principle equal to or greater than the start-of-freezing temperature, to obtain a solution that has an ice grade greater than 0% and less than the maximum grade. The maximum grade is defined as the ice grade obtained at a temperature very much below the start-of-freezing temperature (40° C. below the start-of-freezing temperature for example).
A continuous system includes a heat exchanger in which partial crystallisation takes place by cooling of the phase during the circulation of the solution.
The phase to be crystallised is generally a salt or a solvent in any solution, aqueous or not.
In the case of an aqueous solution, the objective is to form a partially frozen liquid containing fine particles of ice, so that the fluid can always flow in the device under the action of a pump.
Here we give two possible examples of applications in which a partial crystallisation is desired.
A first application example concerns a binary ice or ice slurry, and is used as the cold-bearing fluid in a heat-exchange device. We define “ice slurry” as a mixture with a ratio of about 10 to 70% of ice by weight.
Such binary ices or such ice slurries are generally solutions of water and alcohol and/or of salts and/or of sugars, such as sodium chloride, calcium chloride, potassium chloride, sucrose, etc., for example. The cold-bearing mixtures can also be any fluid capable of storing the cold energy in the form of latent heat by water-ice solidification.
A second application example concerns edible ice creams. For these applications, it concerns partially freezing a preparation containing mainly water and/or milk, fats and/or pieces of fruit, and inserting fine bubbles of air into it. The volume of air to be introduced is more or less equal to the volume of the preparation in the case of an edible ice cream.
Several types of device of previous design allow the implementation of partial crystallisation.
A first type of device is called a “direct-contact generator”. In this type of device, we put the fluid to be crystallised directly in contact with a chilled surface.
A second type of device is called a “vacuum generator”. In this type of device, we keep the fluid to be partially crystallised close to its triple point. The devices of previous design have certain drawbacks however.
The direct-contact generators work by means of mechanical scraping of the crystallised particles on the walls of the exchanger. They therefore have a power that is limited by the power of the mechanical scraping device. They are thus more expensive and complex, due to the presence of rotating parts and mechanisms.
The vacuum generators are very complex, very expensive and very bulky. They are consequently ill suited to the targeted applications, especially in the food area. In fact they are designed for a particular type and volume of production and they are not modular and so not flexible.
PRESENTATION OF THE INVENTION
The invention has as its objective to overcome at least one of the aforementioned drawbacks.
One of the objectives of the invention is to propose a simple technique for the partial crystallisation of a phase in any solution, aqueous or not.
Thus, one of the objectives of the invention is to propose a fairly inexpensive technique for the partial crystallisation of a phase in any solution, aqueous or not.
In particular, one of the objectives of the invention is to propose a device for partial crystallisation using no moving or rotating parts or mechanisms. Another objective of the invention is to propose a device for partial crystallisation which does not maintain the phase to be partially crystallised close to its triple point.
Another objective of the invention is to propose a device for the partial crystallisation of a phase which is modular and of significant unitary power.
Another objective of the invention is to propose a device for the partial crystallisation of a phase which, by virtue of its modularity, can be placed in parallel in order to adapt to several types and volumes of production, in particular in the food area.
To this end, the invention proposes a device for the partial crystallisation of a phase in a solution, comprising at least one pump for circulation of the solution in a circuit of a heat exchanger formed from at least one tube in contact with a cooling circuit, characterised in that the circuit of the exchanger includes one or more means used to control the supercooling amplitude, and means capable of triggering the crystallisation (supercooling rupture) at a precise site located inside the exchanger or in a zone between a first exchanger and a second exchanger in a large exchanger assembly for example.
The crystallisation device also advantageously includes static devices for mixing the solution so that the particles crystallised during the supercooling rupture phenomenon of the flowing solution are continuously mixed with the solution during the circulation of the said solution.
The devices designed to trigger the crystallisation, and the static mixing devices, can comprise elements forming obstacles positioned within the flow (needle, plate, etc.). They can also be changes of direction of circulation of the flow and/or a change of lining of the internal walls of each tube.
The supercooling maintenance, rupture or mixing means can be a combination of the different materials comprising the exchanger or materials positioned in contact with the solution inside the exchanger. The material (as well as its surface state which may be specific) located upstream of the point of rupture in the exchanger, favours the supercooling phenomenon, while the material (as well as its surface state which may be specific) located downstream favours supercooling rupture. Thus, a hydrophobic plastic with a very smooth surface state (low roughness) will tend to delay supercooling rupture and will allow the temperature to be reduced below the start-of-freezing temperature without crystallisation, while a metal with a rough surface state will tend in principle to favour supercooling rupture (triggering of the crystallisation).
The section of the tube can also be variable after the supercooling rupture zone, so that during the phase of growth of the crystals formed during supercooling or during the secondary nucleation phase occurring after supercooling rupture, the flow of the solution whose viscosity will increase markedly and whose apparent density will reduce (volumic expansion due to crystallisation of the water) can flow without the need for excessive upstream pressure.
The fluid is made to circulate at a constant rate or at a fluctuating rate, meaning that the flow phases are followed by phases during which the fluid is immobile or at a lower speed. These fluctuations can be of the on/off type (instantaneous passage from a zero or low speed to a nominal speed) or of the sinusoidal type or indeed of the sawtooth type. It is therefore also possible to circulate the fluid in a succession of flow phases at variable speeds.
The invention also advantageously has the following characteristics, either alone or in any of their technically possible combinations:
the change of direction is an elbow in the circulation circuit, and/or a chicane, and/or at least one change of section inside the circulation circuit; the circuit of the exchanger includes at least one valve used to regulate the flow of the solution; the valve is controlled manually, or is controlled by an independent system of the thermostat type using one or more parameters or the difference between two or more parameters. These parameters can be the input temperature of the solution to be crystallised or a temperature (temperature of the solution, temperature of the tube in the exchanger, temperature of the primary fluid used to cool the exchanger) located at any point situated upstream of the supercooling rupture zone, the output temperature of the solution to be crystallised, or a temperature (temperature of the solution, temperature of the tube in the exchanger, temperature of the primary fluid used to cool the exchanger) at any point located between the supercooling rupture zone and the output of the exchanger, the temperature of the solution at the moment of supercooling rupture, or the flow of the upstream feed, particularly in the case where several devices (exchangers) are fed by the same pump. the circulation circuit includes means for introducing gas bubbles into the solution; the means for introducing the gas are placed in the circulation of the solution or at the walls of a tube.
The invention also concerns an assembly composed of a multiplicity of devices according to the invention or a multiplicity of parts of such a device.
The invention also concerns a method for using such a device.
PRESENTATION OF THE FIGURES
Other characteristics, objectives and advantages of the invention will emerge from the description that follows, which is purely illustrative and not limiting in any way, and which should be read with reference to the appended figured in which:
FIG. 1 diagrammatically represents a possible method of implementation of a device according to the invention;
FIG. 2 diagrammatically represents a method of implementation of a device according to the invention in which on a mixing device has been shown more precisely;
FIGS. 3 to 5 diagrammatically represent several possible methods of implementation of mixing devices;
FIG. 6 diagrammatically represents a longitudinal section of a pipe in a circulation circuit of a device according to the invention; and
FIGS. 7 and 8 diagrammatically represent methods for the implementation of device for introducing a gas into the circulation circuit, and
FIG. 9 diagrammatically represents methods for the implementation of mixing devices inside a tube.
In all of the figures, similar elements carry identical numerical references.
DETAILED DESCRIPTION
As shown diagrammatically in FIGS. 1 and 2 , a possible device according to the invention essentially includes at least one pump 1 used to circulate a solution in a heat exchanger, referenced by the number 2 , and connected at the input to a tank 10 of the solution and at the output to receptacle 3 for the partially crystallised solution.
Each pump 1 is already familiar to the professional engineer. However, the control for the pump, which may or may not be of the measuring type, will allow variation of the fluid flow during the method as a function of one or more regulation systems associated with sensors judiciously positioned in the device.
The fluid is made to circulate at a constant rate or at a fluctuating rate, meaning that the flow phases are followed by phases during which the fluid is immobilised or moves at a lower speed. These fluctuations can be of the on/off type (instantaneous passage from zero or low speed to a nominal speed) or of the sinusoidal type or indeed of the sawtooth type. It is therefore also possible to circulate the fluid in a succession of flow phases at variable speeds.
A valve 4 is placed between the pump 1 and the input of the exchanger 2 , while a valve 5 is placed at the output of the exchanger 2 before receptacle 3 . The valve 5 performs homogeneous mixing of the solution at the output of the exchanger 2 and enables its flow to be adjusted.
Each valve can be controlled manually or by an independent system of the thermostat type using one or more of the following parameters or the difference between two or more parameters. The parameters can be:
the input temperature of the solution to be crystallised, or a temperature (temperature of the solution, temperature of the tube of the exchanger, temperature of the primary fluid used to cool the exchanger) located at any point upstream of the supercooling rupture zone; the output temperature of the solution to be crystallised, or a temperature (temperature of the solution, temperature of the tube of the exchanger, temperature of the primary fluid used to cool the exchanger) at any point located between the supercooling rupture zone and the output of the exchanger, and/or the temperature of the solution at the moment of supercooling rupture or the flow of the upstream feed, in particular in the case where several devices (exchangers) are fed by the same pump.
The heat exchanger 2 mainly comprises a circuit for the circulation 20 of the solution, in contact with a cooling circuit 22 . Thus the pump 1 circulates the solution in the circuit 20 of the exchanger 2 . The length of the circuit is typically of the order of a few meters (from 1 to 5 meters approximately).
An external chilling unit 21 is used to circulate a refrigerated fluid at a negative temperature in the cooling circuit 22 .
By means of the chilling unit 21 and the cooling circuit 22 for the refrigerated fluid, the outer wall of the solution circulation circuit 20 is held at a negative temperature, for example of the order of −5° to −30° Celsius. This negative temperature allows effective refrigeration of the solution contained in the device.
The chilling unit 21 can comprise a system by direct expansion of a refrigerant fluid or any other refrigeration device known to the professional engineer.
The refrigerant fluid circulating in the circuit 22 can be a cryogenic fluid such as liquid nitrogen for example, or a refrigerant fluid used in a mechanical compression appliance.
Note again that the solution can be a cold-bearing liquid for example, or an edible ice cream.
In any event, the solution has to be introduced into the exchanger 2 at a temperature as close as possible to the opening freezing temperature.
As shown more precisely in FIG. 2 , the circulation circuit 20 is mainly composed of tubes 200 . The solution circulates inside the tubes 200 , while the cryogenic or refrigerant fluid used to cool the solution circulates outside the tubes 200 in the circuit 22 .
Preferably, the tubes 200 forming the circuit 20 have a small internal diameter, of the order of 5 to 30 mm for example. Each tube 200 is in a plastic material or in metal or in glass.
The exchanger 2 includes a zone composed of static means to maintain the supercooling in order to delay the appearance of crystals, and a zone composed of static supercooling rupture means to allow the appearance of crystals.
The supercooling maintenance means are used in particular to control the supercooling amplitude. They are placed upstream 5 of the rupture means of course.
To this end, each tube 200 can advantageously comprise a material or is covered by a membrane on its internal surface to form a coating that takes the form of a material and/or a surface state designed to delay the appearance of crystals. The membrane can cover all or part of the internal surface of each tube. The membrane can be formed from a hydrophobic plastic membrane, or glass or a special paint. The surface state can advantageously have a low roughness.
The supercooling rupture means include at least one change of lining of the internal walls of each tube in relation to the maintenance means, and/or at least one change of direction of the circulation of the solution, and/or at least one obstacle to the circulation of the solution on the internal walls of each tube.
FIG. 3 shows that the change of direction of the circulation of the solution can take the form of and elbow 201 in the tubes. Each elbow 201 does not necessarily execute a 180-degree turn in the circulation 6 of the solution, but can simply impose a change of direction on the circulation circuit 20 . In general, a change of direction can mean any device in the circulation circuit 20 such as the generator of the internal surface of a portion of rectilinear tube located upstream over a minimum length of 10 times the diameter of the tube forming a rupture angle of more than about 5 degrees in relation to a portion of tube downstream.
FIG. 4 shows that the change of direction can also take the form of a chicane 202 . The rupture angle is thus equal to 90 degrees in this case.
FIG. 5 shows that the change of direction can also be a change of section 203 of the tube 200 in the circulation circuit 20 .
The change of section 203 is preferably a shrinkage of the section. The shrinkage 203 is preferably local, with the section of the tube upstream and downstream of the shrinkage 203 being more or less the same. The shrinkage takes place over a length which is more or less equal to 3 times the diameter of the tube 200 before the shrinkage.
FIG. 9 shows that the obstacles 207 and 208 positioned within the tube 200 can form the supercooling rupture means. The obstacles can take the form of plates for example, or of fins 207 or 208 lying perpendicularly to the inner wall of the tube 200 or obliquely. The obstacles 207 or 208 can have many different shapes. They can also take the form of needles for example. The obstacles 207 and 208 are attached or made from the material of the walls of the tube 200 .
The change of lining of the internal walls takes the form of a change of material and/or a change of the surface state, designed to interrupt the supercooling and allow the appearance of crystals. The material of the rupture means is preferably a metal. The change of surface state at the rupture means takes the form of greater roughness.
The mixing devices can include at least one non-stick coating on at least one part of the internal walls of each tube 200 , and/or at least one change of direction of the circulation of the solution, and/or at least one obstacle 207 , 208 to the circulation of the solution on the internal walls of each tube.
The non-stick coating can take the form of a membrane on the internal surface of the tubes. The membrane can cover all or part of the internal surface of each tube. The objective of the membrane is to limit sticking of the particles of ice formed during the crystallisation onto the walls of the tubes 200 .
FIG. 2 shows an example of the presence of the static mixing devices—here referenced by 201 —in the circuit 20 of the exchanger 2 used to continuously mix the crystallised particles at the wall inside the circuit 20 to all of the solution at or after the point of rupture.
FIG. 2 shows only a single mixing device. Of course, the exchanger can include several mixing devices placed along the circuit 20 .
During the heat exchanges, the crystallised particles are at the inner wall of the tubes 200 and form a crown.
The mixing devices are used to unstick the crown of crystallised particles and thus to allow mixing of these particles at the central part of the solution in circulation.
Several methods of implementation of mixing devices are possible.
FIG. 3 shows that the mixing devices of the circuit 20 can take the form of an elbow 201 in the tubes. Each elbow 201 does not necessarily execute a 180-degree turn in the circulation 6 of the solution, but can simply impose a change of direction on the circulation circuit 20 .
In general, a “mixing device” refers to any device in the circulation circuit 20 , such as the generator of the internal surface of a portion of rectilinear tube located upstream over a minimum length of 10 times the diameter of the tube forming a rupture angle of more than about 5 degrees in relation to a portion of tube downstream.
FIG. 4 shows that the mixing devices can also take the form of a chicane 202 . The rupture angle is thus equal to 90 degrees in this case.
FIG. 5 shows that the mixing devices can also be a change of section 203 of the tube 200 in the circulation circuit 20 . The change of section 203 is preferably a shrinkage of the section. The shrinkage 203 is preferably local, with the section of the tube upstream and downstream of the shrinkage 203 being more or less the same. The shrinkage takes place over a length that is more or less equal to 3 times the diameter of the tube 200 before the shrinkage.
FIG. 9 shows that the mixing devices can also be obstacles 207 and 208 positioned within the tube 200 . The obstacles can take the form of plates for example, or of fins 207 or 208 lying perpendicularly to the inner wall of the tube 200 or obliquely. The obstacles 207 or 208 can have many different shapes. They can also take the form of needles for example.
The obstacles 207 and 208 are attached or made from the material of the walls of the tube 200 .
The obstacles 207 and 208 constitute mixing devices. Note again that they can also constitute the device used to control the crystallisation triggering zone. This is the case in particular of needles.
FIG. 6 shows that the internal diameter of the circulation circuit 20 is not necessarily constant throughout the circulation circuit.
The density of the solution reduces in parallel with the crystallisation, in particular because ice has a specific volume which is greater than that of water for example.
Thus, it is judicious to increase the section of the tube 200 of the circuit 20 at the moment of freezing of the phase in the solution, in order to facilitate its circulation.
Moreover, a change to the section of passage of the tubes 200 constituting the circuit leads to a change in the speed of circulation and in the pressure of the solution.
The change to the speed of circulation influences the contact time between the solution and the cooled internal surface of the tubes 200 . It is possible therefore to act upon this parameter in order to control the speed of crystallisation of the solution.
Furthermore, a change in the pressure of the solution also results in a greater degree of crystallisation, as described in the reminder of this present description.
Note again that during the circulation of the solution in the exchanger 2 , crystallisation takes place mainly by heat exchange at the walls between circuit 20 and circuit 22 .
Advantageously however, and as shown in FIGS. 7 and 8 , it is possible to introduce gas into the solution in the form of micro-bubbles.
The expansion of the micro-bubbles of air or nitrogen introduced into the solution produces a refrigeration effect which also contributes to the crystallisation of the phase of the solution.
A change in the pressure of the solution therefore results in an expansion of the micro-bubbles of gas in the solution.
This gas is preferably dinotrogen (N 2 ), or air in the case of edible ice creams. We therefore get the formation of an emulsion or of a foam in the circuit 20 .
As shown in FIGS. 7 and 8 , the gas is introduced into the circulation circuit 20 by means of nozzles 205 and 206 .
FIG. 7 shows a first method of implementation of a nozzle 205 according to which a conduit 8 is introduced into the circulation 6 of the solution through the wall of the tube 200 more or less perpendicularly to the circulation 6 . The conduit 8 is elbowed in the direction of the circulation and so that the extremity of the conduit 8 is more or less parallel to the circulation 6 , over a length equal to 2 or 3 times the diameter of the tube 200 upstream of the conduit 8 for example. Microperforations 206 at the extremity of the conduit 8 allow the release of the micro-bubbles of gas in a homogeneous manner into the solution 6 .
A widening 204 of the section of the tube 200 is advantageously executed opposite to the extremity of the conduit, so that the expansion of the gas in the solution is facilitated, because of the change to the speed of circulation of the solution and to its pressure.
FIG. 8 shows a second method of implementation of a nozzle 206 according to which a conduit 8 is used to introduce the gas into a balance chamber 9 set on the outer wall of the tube 200 of the circuit 20 .
The chamber 9 extends approximately over a length which is more or less equal to 3 to 5 times the diameter of the tube 200 , the diameter being that upstream of the conduit 8 .
Microperforations 206 between the chamber 9 and the wall of the tube 200 allow the release of the micro-bubbles of gas in a homogeneous manner into the solution 6 .
A widening 204 of the section of the tube 200 is advantageously executed opposite to the extremity of the conduit, so that the expansion of the gas in the solution is facilitated by means of the change to the speed of circulation of the solution and to its pressure.
In both cases, the gas is introduced under pressure into the solution.
The gas can also be introduced into the solution before the latter enters into the exchanger 2 , and before or after the circulation pump 1 . This then results in the freezing of the emulsion already containing the micro-bubbles of gas.
Naturally several tubes 200 can be placed in parallel in order to increase the rate of flow by weight in the device, or in order to create ice creams of different flavours for example.
Thus, the device can be modular, and can include several exchangers according to the invention, with one or more circulation pumps, the power then being adapted by the number of tubes.
It is thus possible envisage a construction in the conventional radiator form of the exchanger according to the invention, with a direct expansion on the exterior of the tubes.
Tests have shown that one possible device according to the invention can have a flow of about 90 g/minute of ice slurry exiting with an ice grade of between 30% and 50% for an initial water-alcohol solution of 10% by weight. The output temperature of the ice slurry is approximately −5 to −10° C.
In the device on which the tests were conducted, the internal diameter of the tube is equal to 8 mm and the length of the tube is equal to 4 meters. This develops a power per tube of about 270 W.
The power is therefore high, and the device quite inexpensive, since it is of simple design. In fact it has no moving mixing device.
The device is therefore advantageously, though not limitatively, used in the food area for the production of ice creams, and in the area of refrigerant fluid production, in particular for the production of air-conditioning devices. | The invention relates to a device for the partial crystallization of a phase in a solution, comprising at least one pump for circulation of the solution in a circuit of a heat exchanger formed from at least one tube in contact with a cooling circuit, characterized in that the circuit of the exchanger includes static means to mix the solution, so that the crystallized particles of the phase are continuously mixed with the solution during the circulation of said solution. The invention also relates to an assembly including several devices according to the invention or several parts of such a device. The invention also relates to a method to use such a device. | 1 |
FIELD OF THE INVENTION
[0001] The present invention relates in general to impact copolymers and more specifically to a polypropylene having a bimodal rubber particle size distribution. The polypropylene impact copolymers of the present invention achieve a desirable balance between stiffness and impact strength.
BACKGROUND OF THE INVENTION
[0002] Those skilled in the art realize that rubber phase characteristics, such as rubber particle size, particle size distribution, particle morphology, rubber phase volume and degree of interfacial adhesion between rubber particles and matrix polymer significantly influence the properties of impact modified polymers. The optimization of these characteristics is critical in obtaining desirable polymer performance particularly in terms of impact strength, toughness, stiffness, and gloss.
[0003] Various efforts have been made to develop rubber-modified polymers having a balance between the properties of impact strength, stiffness and gloss since the introduction of rubber-modified thermoplastics. The concept of bimodal rubber particle size distribution was explored in styrene-containing polymers such as high impact polystyrene and acrylonitrile-butadiene-styrene (“ABS”) in the early 1980's. It was demonstrated that a bimodal rubber particle size distribution in high impact polystyrene provides a stiffness-ductility balance while maintaining high gloss. This is accomplished by the presence of small amounts (typically 2-10%) of large sized (5-15 μm) rubber particles in small sized (0.2-1 μm) rubber particles. Such materials were developed to compete with costly ABS materials.
[0004] As a general rule in rubber-modified styrene-containing polymers at a given rubber concentration, the larger the rubber particles, the higher the impact properties, but the poorer the stiffness and gloss. Those higher impact properties were attributed to the more efficient use of rubber phase. The converse has been reported for impact modified polypropylene prepared via melt blending, i.e., the smaller the rubber particles, the higher the impact strength, above 0.5 μm, for a given rubber concentration. (See, B. Z. Jang et al., Poly. Eng. and Sci., 25, 643 (1985)). Because no craze formation was observed when the rubber particles were smaller than 0.5 μm, the materials had lower impact properties. Crazes are a large number of tiny voids formed in an attempt to release applied energy. The differences between rubber-modified styrene-containing polymers and melt blended polypropylene may be attributed to the existence and/or the amounts of inclusions within rubber particles as well as such fracture mechanisms as crazing and shear yielding. Effects of rubber concentration and particle size on notched Izod and brittle transition temperature of rubber modified polypropylene have been reported in A. van der Wal et al, Poly. Mater. Sci. Eng., 70, 189, (1993).
[0005] Therefore, a need exists in the art for an impact polypropylene copolymer with a bimodal rubber particle size distribution which will overcome the above-listed deficiencies. The present invention provides an impact copolymer which exhibits a good balance between the properties of stiffness and impact strength.
SUMMARY OF THE INVENTION
[0006] The present invention provides a composition comprising at least about 80% of a first polypropylene having dispersed therein rubber particles of first size and a second polypropylene having dispersed therein rubber particles of a size greater than the first size.
[0007] The present invention further provides a composition comprising at least about 80% of a first polypropylene having dispersed therein rubber particles of a first size, a second polypropylene having dispersed therein rubber particles of a size greater than the first size and a third polypropylene having dispersed therein rubber particles of a size greater than the first size.
[0008] The present invention yet further provides a method of making an impact copolymer, the method comprising combining a first polypropylene having dispersed therein rubber particles of a first size and a second polypropylene having dispersed therein rubber particles of a size greater than the first size wherein the first polypropylene comprises at least about 80% of the impact copolymer.
[0009] The present invention still further provides a method of making an impact copolymer, the method comprising combining a first polypropylene having dispersed therein rubber particles of a first size with a second polypropylene having dispersed therein rubber particles of a size greater than the first size and with a third polypropylene having dispersed therein rubber particles of a size greater than the first size, wherein the first polypropylene comprises at least about 80% of the impact copolymer.
[0010] These and other advantages and benefits will be apparent from the Detailed Description of the Invention herein below.
BRIEF DESCRIPTION OF THE FIGURES
[0011] The present invention will now be described for purposes of illustration and not limitation in conjunction with the following figures, wherein:
[0012] [0012]FIG. 1 a is an atomic force micrograph of commercially produced impact copolymer Ti4040G,;
[0013] [0013]FIG. 1 b is an atomic force micrograph of commercially produced impact copolymer Ti4900M;
[0014] [0014]FIG. 1 c is an atomic force micrograph of commercially produced impact copolymer Ti5995C;
[0015] [0015]FIG. 2 illustrates the effect on impact properties of the addition of either Ti4040G or Ti4900M to Ti5995;
[0016] [0016]FIG. 3 demonstrates the effect on flexural modulus of the addition of either Ti4040G or Ti4900M to Ti5995;
[0017] [0017]FIG. 4 illustrates the effect on surface gloss of rubber particle size and ethylene content;
[0018] [0018]FIG. 5 demonstrates the effect on surface gloss of Ti4040G and/or Ti4900M in Ti5995;
[0019] [0019]FIG. 6 illustrates the effect on instrument impact and flexural modulus of rubber particle size;
[0020] [0020]FIG. 7 a illustrates the effect on instrument impact and flexural modulus of Ti4040G in Ti5995;
[0021] [0021]FIG. 7 b illustrates the effect on instrument impact and flexural modulus of Ti4900M in Ti5995;
[0022] [0022]FIG. 8 demonstrates the effect of Ti4040G in Ti4900M and Ti5995; and
[0023] [0023]FIG. 9 compares the effect on instrument impact and flexural modulus of rubber particle size and Ti4040G or Ti4900M in Ti5995.
DETAILED DESCRIPTION OF THE INVENTION
[0024] The present invention will now be described for the purposes of illustration and not limitation by the following examples.
[0025] The commercial impact copolymers used herein have the characteristics as given in Table 1 , where Ti5995 powder, which is the same powder as Ti5900C, was compounded with basic antioxidants as known in the art. The bimodal rubber particle size distributions have been prepared by melt blending two copolymers having different sizes of rubber particles.
TABLE I Some Properties of Impact Copolymers Property Ti5995 Ti4900M Ti4040G % C 2 3.0 5.5 8.0 % XS 6.6 9.7 Rubber particle size a (μm) 0.2-0.4 1-1.5 3-5
[0026] The following tests were conducted: Differential Scanning Calorimetry (DSC); tensile properties of each copolymer were determined by ASTM D638; the flexural modulus was determined by ASTM D790; the Izod Impact was determined by ASTM D256; gloss was determined by ASTM D2457; and instrumented impact @ 4° C. was determined by ASTM D3763.
[0027] Aristech Chemical Corp. makes commercial impact copolymers having various rubber particle sizes as shown in the atomic force micrographs (AFM) FIGS. 1 a , 1 b and 1 c . The rubber particle size of one of those impact copolymers herein designated “Ti5900C” and shown in FIG. 1 c (base polypropylene powder is the same as Ti5995), was estimated from the micrograph to be about 0.2-0.4 μm The rubber particle size of another herein designated “Ti490OM”, shown in FIG. 1 b was estimated to be about 1-1.5 μm and that of a third herein designated as “Ti4040G”, shown in FIG. 1 a , was estimated to be about 3-5 μm. It should be noted that FIGS. 1 a , 1 b , and 1 c are micrographs of each commercial impact copolymer at two different magnifications. To produce a blend with a bimodal rubber particle size distribution, small amounts of Ti4040G or Ti4900M were incorporated into Ti5995 by conventional methods practiced in the art such as but not limited to: melt blending and reactor blending via polymerization. The compositions and properties of impact copolymers and their blends are given in Table II.
[0028] As can be appreciated by reference to Table II, the rubber particle size depends on the rubber concentration of the impact copolymer, i.e. ethylene content. The melt flow rate (MFR) of the blend decreased with increasing amounts of Ti4040G in Ti5995, and the crystallinity of the blend decreased with increasing ethylene contents.
TABLE II Various polymer blends of Ti5995 with Ti4040G and/or Ti4900M Comp. Comp. Comp. Ex. Ex. Ex. Ex. Ex. 1 Ex. 2 Ex. 3 4 5 6 7 Ti4040G 100 10 20 10 Ti4900M 100 20 10 Ti5995 100 90 80 80 80 MFR (grams/10 min) 3.9 95 136 118 80 145 105 % C 2 8.0 5.5 3.0 3.6 4.1 3.4 3.9 T m (° C.) 162.3 162.9 161.2 161.4 161.5 162.5 162.5 T c (° C.) 115.5 122.1 115.5 116.4 115.8 120.7 119.8 X c (%) 48.5 57.4 57.8 56 54.5 58.5 57.5 Rubber particle 3-5 1-1.5 0.2-0.4 — — — — size a (μm) Tensile stress at 3700 4094 4243 4318 4190 4364 4318 yield (psi) Tensile Strain at 8.6 4.5 5.6 5.5 5.9 4.9 5.4 yield (%) Tensile Modulus 185.2 252.0 237.6 243.4 233.0 256.4 245.1 (kpsi) Flexural Modulus 174.7 214.1 202.5 206.0 198.5 214.6 213.1 (kpsi) Notched Izodn 2.59 0.79 0.55 0.68 0.78 0.56 0.73 (ftlb/in) 20° Gloss 67.6 74.7 77.8 77.3 79.9 78.7 78.4 60° Gloss 81.8 83.9 87.9 88.6 88.8 88.1 88.3 Instrumented Impact @ 32.6 2.9 0.7 1.6 1.7 1.2 1.7 4° C. (ft-lb)
[0029] The ethylene contents of the blends increase with the addition of impact copolymers having larger rubber particles such as TI4040G and TI4900M, thus increasing impact properties of the blends as shown in FIG. 2.
[0030] The addition of 10-20% Ti4040G to Ti5995 (Examples 3 and 4) slightly improved the tensile yield stress and flexural modulus as shown in FIG. 3. The addition of 10-20% Ti4900M to Ti5995 (Examples 5 and 6) increased flexural modulus. It is interesting to note that the flexural moduli of the compounds containing Ti4900M are the same as that of Ti4900M alone. The surface gloss decreased with increasing size of rubber particle or ethylene content as is shown in FIG. 4. The addition of 10-20% Ti4040G (Examples 3 and 4) or Ti4900M (Example 6) did not affect the surface gloss of the blends, although the ethylene content increased as shown in FIG. 5.
[0031] In order to demonstrate the effect of Ti4040G in Ti5995 in more detail, the impact properties and flexural moduli were normalized with the ethylene content of the compound and this relationship is depicted in FIG. 6. As shown in FIG. 6, Ti4040G alone has low modulus and high impact whereas Ti5995 has high modulus and low impact. By adding small amounts of Ti4040G to Ti5995, a better impact property-modulus balance, i.e., higher impact for given flex modulus or higher modulus for given impact, can preferably be obtained. In summary, the addition of small amounts of large rubber particles (3-5 μm or 1-1.5 μm) to small rubber particles (0.2-0.4 μm) provides a better property balance between impact and stiffness. The addition of 10-20% Ti4040G to Ti5995 increased the instrument impact at 4° C. from 0.7 to 1.7 ft-lb while maintaining flexural modulus at 200 kpsi and surface gloss at 80/90 (20/60° C. gloss). The addition of 10-20% Ti4040M to Ti5995 increased both flexural modulus and instrument impact at 4° C. Without being limited to any specific theory, the inventor believes that these results are the manifestation of synergistic effect of bimodal rubber particle size distribution in impact polypropylene. This synergistic effect of a bimodal rubber particle distribution, which is known to those skilled in the art to exist in styrene-containing polymers, i.e., glass polymers, also appears to exist in impact polypropylene, i.e., a semi-crystalline polymer.
[0032] To further elucidate the structure-property relationship of bimodal rubber particle size distribution on the properties of impact copolymers, Ti 4040G (3-5 μm) was added to Ti4900M which has larger rubber particles than Ti5995 (1-1.5 μm vs. 0.2-0.4 μm). The effects of the presence of large rubber particles in small rubber particles on impact properties, flexural for the molded parts were assessed and are reported in Table III. As shown in FIGS. 7 to 9 , the flexural mod ulus of the matrix material, Ti4900M was maintained at 210 kpsi and the instrumented impact at 4° C. increased from 2.9 ft.lb to 8.8 ft.lb by the addition of 20% Ti4040G. As can be appreciated by reference to Table III, the MFR of the melt blend decreased with increasing amounts of Ti4040G in Ti4900M. The crystallinity of the blend decreased with increasing ethylene contents.
TABLE III Various polymer blends of Ti4900M with Ti4040G Comp. Ex. Comp. Ex. Ex. Ex. Ex. 8 9 10 11 12 Ti4900M 100 95 90 80 Ti4040G 100 5 10 20 MFR 95 3.9 82 70 50 (grams/10 min) % C 2 5.5 8.0 5.74 5.89 6.24 T m (° C.) 1-1.5 3-5 T c (° C.) 162.9 162.3 163.4 163.4 163.5 X c (%) 122.1 115.5 122.3 122.2 121.9 Rubber 57.4 48.5 56.5 56.1 55.9 particle size a (μm) Tensile 4094 3700 4151 4130 4094 stress at yield (psi) Tensile 4.5 8.6 4.4 4.5 4.9 Strain at yield (%) Tensile 252.0 185.2 288 287 277 Modulus (kpsi) Flexural 214.1 174.7 214 215 210 Modulus (kpsi) Notched 0.79 2.59 0.93 0.96 0.97 Izodn (ftlb/in) Inst-Impact @ 2.9 32.6 5.1 7.6 8.8 4° C. (ft-lb)
[0033] The impact properties and flexural modulus were normalized with the ethylene content of the compound and this relationship is depicted in FIG. 10. It should be noted that the values given in FIG. 10 are per unit ethylene content. As shown in FIG. 10, Ti4040G has low modulus and high impact while Ti5995 has high modulus and low impact and Ti4900M has medium impact and modulus per unit ethylene. By adding small amounts of Ti4040G either to Ti4900M or to Ti5995, a better impact property-modulus balance, i.e., higher impact for given flex modulus can preferably be obtained. The results appear to indicate the presence of a synergistic effect of bimodal rubber particle size distribution in impact polypropylene. As can be seen with reference to FIG. 10, the improvement in instrumented impact was much higher for Ti4900M than for Ti5995. This was about 300% improvement over Ti4900M in comparison to 240% for Ti5995. Without being limited to any specific theory, the inventor believes that these results suggest that the size of the rubber particle of the matrix polymer plays an important role to the degree of improvement in impact properties.
[0034] As will be readily apparent to those skilled in the art upon review of the data and figures included herein, the addition of small amounts of large sized rubber particles to small rubber particles improved impact properties of the blended impact copolymer polypropylenes while maintaining stiffness of the matrix material. The difference between small and large rubber particles appears to be an important factor in controlling the properties of impact polypropylene having a bimodal distribution of rubber particles.
[0035] As demonstrated herein, it is possible to significantly improve the impact property of impact polypropylene while maintaining stiffness of the matrix material by using various combinations of rubber particles. Although impact copolymers having rubber particles larger than 3-5 μm are currently unavailable, the inventor contemplates the use in the present invention of copolymers having rubber particles larger than 3-5 μm.
[0036] The foregoing illustrations of embodiments of the present invention are offered for the purposes of illustration and not limitation. It will be readily apparent to those skilled in the art that the embodiments described herein may be modified or revised in various ways without departing from the spirit and scope of the invention. The scope of the invention is to be measured by the appended claims. | Polypropylene impact copolymers and methods of making them are provided. These impact copolymers achieve a balance between stiffness and impact strength and additionally higher gloss by the inclusion therein of a bimodal distribution of rubber particles. | 2 |
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of priority under 35 U.S.C. §119 of German Patent Application DE 10 2005 039 236.9-16 filed Aug. 19, 2005, the entire contents of which are incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The invention relates to an air exit guidance, in particular for the arrangement in the personal service unit of a passenger aircraft.
BACKGROUND OF THE INVENTION
[0003] Common ventilation nozzles, as are for example arranged at present in the personal service units of passenger aircraft and passenger buses, as well as the dashboards of motor vehicles, create flow noises during use, which are perceived by many passengers to be unpleasant and annoying.
SUMMARY OF THE INVENTION
[0004] Against this background, it is the object of the present invention to create a simply constructed air exit guidance which is uncomplicated in its manufacture and is improved with regard to the emission of noise.
[0005] According to the invention, an air exit guidance is provided, in particular arranged in the personal service unit of a passenger aircraft or an air guidance system of a passenger aircraft or other vehicle is provided. The air exit guidance includes an air inlet, an air outlet and an adjustable throttle means, wherein the throttle means is arranged at the inflow side of the air exit guidance.
[0006] The inventive air exit guidance feature forms the end of the ventilation system on the downstream side, with which the passengers in a passenger aircraft or in a vehicle are supplied with a ventilation flow. In particular it is provided for the arrangement in the personal service unit of a passenger aircraft, but may for example also be arranged in corresponding installations of a passenger bus or motor vehicle. The air exit guidance comprises an air inlet and an air outlet. The air exit guidance is connected by channel to the ventilation system via the air inlet, and the air outlet forms the downstream-side end of the air exit guidance to the surroundings to be ventilated. Also, the air exit guidance comprises an adjustable throttle means, with which the air quantity which is let out at the air outlet, or the airflow, may be changed, in particular with which the air exit guidance may also be closed.
[0007] According to the invention, the throttle means is provided at the inflow-side of the air exit guide. With this arrangement, the throttle means within the air exit guidance is arranged at an as large as possible distance to the air outlet, and the flow path of the air from the throttle means to the air outlet is almost just as long as the flow path through the complete air exit guidance. This design has the advantage that the intensity of the sound caused by the throttle means and perceivable at the air exit, is reduced, since the air as the carrier of sound within the air exit guidance, proceeding from the throttle device as a sound source, has to cover a very large flow path up to the air outlet, wherein the sound intensity weakens on the way to the air outlet. A further advantage of this arrangement is the fact that with an air exit guidance installed in a fitting, for example in a personal service unit, the throttle means is arranged in a region which is located within the fitting or the personal service unit, which then also serves as an outer sound insulation feature.
[0008] In a further advantageous design, with the air exit guidance, several air guidance channels to the air outlet are provided downstream of the throttle device. The air outlet is advantageously formed by the exit openings of the air guidance channels themselves. The air guidance channels form the flow conduits from the throttle means to the air outlet to the surroundings. Preferably, the air guidance channels are arranged parallel to one another. The use of several air guidance channels has the advantage that the inner walls of the air guidance channels together form a larger surface onto which the airflow flows, than this would be the case for example with a single air guidance channel with a correspondingly large cross section. This is particularly advantageous since the air columns located in the air guidance channels, which are set into oscillation by the sonic excitation at the throttle means, come across a significantly larger friction surface at which friction losses arise, which are then taken from the sonic energy. The sound intensity reduces in this manner, i.e. the air guidance channels from a sound absorber.
[0009] Preferably, the air guidance channels are arranged in a manner such that the exit openings of the air guidance channels, which from the air outlet to the surroundings have such a distance to one another, that the air oscillations exiting at the exit openings superimpose outside the air exit guidance in a free jet, and by way of this mutually weaken one another, and in the most favorable case even cancel each other out.
[0010] The air guidance channels are advantageously designed as long as possible, since they form resonance channels, with which, with an increasing length, the natural resonances of the air columns oscillating therein are displaced into lower frequency regions, which given the same sonic pressure are perceived by the human ear to be quieter than higher frequency ranges.
[0011] It is known that with the sonic excitation at an edge onto which an airflow flows, the sound intensity as well as the frequency of the produced sound reduce with a decreasing flow speed. For this reason, the air inlet of the air exit guidance according to the invention usefully runs out into a diffuser space. The diffuser space is designed in a manner such that on the exit side of the air inlet, it forms a space with a flow cross section which is significantly reduced with respect to the air inlet, in which the flow speed is reduced at the exit side of the air inlet. Advantageously the diffusor space is arranged on the entry side of the throttle means, so that air whose flow speed is reduced with respect to the flow speed directly at the exit side of the air inlet, flows onto the throttle means.
[0012] The air inlet is preferably formed by several air inlet openings. These are preferably arranged parallel and offset to the air guidance channels. Advantageously, the air inlet openings are positioned in a manner such that they run into the diffuser space, at a distance to the air guidance channels. The air inlet openings are particularly preferably arranged such that the airflow led through the air inlet openings is not directed directly onto an edge located in the air exit guidance, in particular onto an edge of the throttle means. By way of this, a direct production of sound by the airflow exiting at the air inlet openings is prevented.
[0013] In one advantageous embodiment of the invention, the air inlet, the throttle means, the air guidance channels as well as the air outlet are arranged in a flow guidance component which is pivotably mounted in a mounting- and fastening element in any direction. The flow guidance component preferably contains the complete flow path from the air inlet to the air outlet. The mounting- and fastening element may be designed as a separate component for installation into a fitting, or for example the personal service unit of a passenger aircraft. Apart from this, it is also possible for the mounting- and fastening element to be part of a fitting or a personal service unit. The flow guidance component is arranged and mounted within the mounting- and fastening element such that it is pivotable with respect to the mounting- and fastening element about at least two pivot axes. In this manner, airflow exiting from the air outlet may be directed in a targeted manner.
[0014] Advantageously, the flow guidance component and the mounting- and fastening element form a ball joint for this. Thus the mounting- and fastening element may be designed in a manner such that it forms a hollow-ball-shaped bearing cup, in which the flow guidance component, which at least in sections has an outer shape which is complementary to the hollow-ball-shaped receiver space of the mounting- and fastening element, is arranged with a slight play.
[0015] The flow guidance component is preferably designed of two parts. Thereby, the flow guidance component comprises a first component on which the air inlet is provided, and a second component, in which the air guidance channels are arranged. In this manner, the complete flow guidance component may be manufactured in an inexpensive manner for example from two plastic injection molded parts, without further components being necessary.
[0016] Advantageously, the first and the second component are movable relative to one another, and form the throttle means. Thus the first component and the second component form a throttle valve, with which preferably the first component forms a closure body with which the flow cross section of the flow path from the air inlet to the air guidance channels may be changed.
[0017] The air guidance channels are particularly advantageously closable on the inflow side indirectly or directly by a wall of the first component. Preferably, the air guidance channels are arranged in the second single-piece component, which is movable such that on the one hand it may be moved into a position distanced to the inner wall of the first component and in which a flow path from the air inlet to the air guidance channels exists, and on the other hand may be moved into a position in which the second component sealingly bears on the inner wall of the first component and thus closes the air guidance channels on the inflow side.
[0018] In an advantageous manner, the first and the second component form the diffuser space in the assembled condition of the flow guidance component. The diffuser space is arranged in the flow guidance component in a manner such that it surrounds the air guidance channels preferably in an annular manner. For example, the second component may be designed in a pot-like manner, wherein the air guidance channels, proceeding from the middle of the inner base of the second component, extend in its longitudinal direction. The first component is preferably designed such that it covers the open pot end of the second component. The annular space which arises on assembly of the first and second component, thereby forms the diffuser space.
[0019] In a preferred embodiment, the first component is designed as an outer component in the form of a ball section. In this manner, the flow guidance component may be arranged in the mounting- and fastening element in the manner of a ball joint. It is further preferable to arrange a threaded stem in the inside of the first component, onto which the second component may be screwed in an adjustable manner. Thus the second component may be adjustable in the axial direction by way of rotation with respect to the first component.
[0020] Usefully, the second component has a handle with which the second component is movable relative to the first component in the direction of a middle axis of the flow guidance component. The handle thereby is arranged at a position of the air exit guidance which is easily accessible to the user. In a preferred embodiment, the handle is designed for rotating the second component with respect to the first component, wherein the second component is screwed on the first component in an adjustable manner.
[0021] The invention is hereinafter described by way of an embodiment example represented in the drawing. The various features of novelty which characterize the invention are pointed out with particularity in the claims annexed to and forming a part of this disclosure. For a better understanding of the invention, its operating advantages and specific objects attained by its uses, reference is made to the accompanying drawings and descriptive matter in which a preferred embodiment of the invention is illustrated.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] In the drawings:
[0023] FIG. 1 is a sectioned view of an air exit guidance with a closed throttle means; and
[0024] FIG. 2 is a sectioned view of the air exit guidance according to FIG. 1 , with an opened throttle means.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0025] Referring to the drawings in particular, the air exit guidance system of the invention includes a flow guidance component 2 as well as a mounting and fastening part 4 , in which the flow guidance component 2 is mounted. The flow guidance component 2 is formed in a two-part manner with a first component (ball part) 6 which receives a second component (actuator part) 8 .
[0026] The first component 6 is designed in an essentially hollow manner and has an outer shape which corresponds to a ball with a cut-off spherical cap. The component 6 thus comprises a circular, open end-side 10 . Proceeding from this end-side 10 , the inner space of the component 6 is firstly designed in a cylindrical-hollow manner, in order then to run into a calotte-shaped, closed region. A threaded stem 12 extends on this calotte-shaped region of the inner space from the inner wall of the component 6 in the direction of the open end-side 10 . Thereby, the threaded stem 12 has a longitudinal axis A which runs through the middle of the end-side 10 .
[0027] The second component 8 is designed in a pot-like manner and has an outer diameter which corresponds to the inner diameter of the mounting- and fastening component 4 in its hollow-cylindrical region. The pot-like component 8 on the inside has a stem 14 which extends from the base of the component 8 and which is arranged centrally of the cylindrical outer wall and projects beyond this. A threaded pocket hole 16 is formed at the free end of the stem 14 , into which hole the threaded stem 12 of the component 6 engages.
[0028] The threaded stem 12 is screwed into the threaded pocket hole 16 in the assembled condition of the flow guidance component 2 . In an end position, the stem 14 , as shown in FIG. 1 , abuts with its end-side against the inner wall of the component 6 in its calotte-shaped region and bears on its inner wall in a sealing manner. In the assembled condition of the flow guidance component 2 , the outer wall of the component 8 has a slight play with the inner wall of the component 6 in its hollow-cylindrical region. A sealing ring 18 which is arranged on the outside in the region of the free end of the outer wall of the component 8 thereby seals the component 6 with respect to the component 8 .
[0029] A diffuser space 20 is formed within the components 6 and 8 , which extends annularly around the stem 14 from the component 8 and is limited on the outside essentially by the outer wall of the component 8 , and above its free end by the inner wall of the component 6 , which is designed in a calotte-shaped manner.
[0030] Several recess 22 which form air inlet openings passing through the outer wall of the component 6 are distributed parallel to the middle axis A and annularly about the middle axis A, in the component 6 . The recesses 22 with the flow guidance component 2 run out into the diffuser space 20 and specifically next to the stem 14 . They form a flow connection from outside the flow guidance component 2 to the diffuser space 20 .
[0031] Several air guidance channels 24 which form resonance channels are arranged in a circular manner about the threaded pocket hole 16 on the component 8 . These air guidance channels 24 extend from the end-face of the stem 14 to the free end-face of the component 8 on the base, where they form exit openings 36 . In each case, adjacent exit openings 36 thereby have a distance to one another, which is dimensioned such that the airflows exiting there during operation of the air exit guidance, and thus also the air oscillations, superimpose, and the air oscillations partly mutually cancel one another in this manner, by which means the sound emission is further reduced.
[0032] The mounting- and fastening component 4 is designed as a hollow body of revolution, open at two opposite sides. Proceeding from an air inlet 26 , the inner space of the mounting- and fastening component 4 is firstly designed in a cylindrical manner, in order subsequently to widen in the shape of a ball segment. This section of the inner space of the mounting- and fastening component which is hollowed out in a ball-segment-shaped manner serves for receiving the flow guidance component 2 . Accordingly, the ball-segment-shaped section of the mounting- and fastening element 4 is designed such that it corresponds to the spherical outer shape of the outer component 6 of the flow guidance component 2 .
[0033] The flow guidance component 2 is mounted in the mounting- and fastening component 4 with little play in the manner of a ball joint, so that it is rotatable in all directions B, and is pivotable in a limited manner in any directions C. A sealing ring 34 is arranged between the outer wall of the component 6 as well as the inner wall of the mounting- and fastening part 4 .
[0034] While the component 6 of the flow guidance component 2 in the installed condition terminates essentially flush with the mounting- and fastening component 4 , the region around the free end-face at the base of the component 8 projects out of the mounting- and fastening component 4 . A region of the component 8 is designed as a handle 30 in a shouldered manner, with which the component 8 may be rotated relative to the component 6 , in order to be able to move the flow guidance component 2 from a closed position shown in FIG. 1 , into the opened position represented in FIG. 2 , or into any intermediate position.
[0035] The mounting- and fastening component 4 forms the outflow-side end of a ventilation system which is not represented in the figures, with which it is conductingly connected via the air inlet 26 . Air flows from the ventilation system onto a region 28 extending from the air inlet 26 to the flow guidance component 2 . Air firstly flows into the diffuser space 20 via the recesses 22 . As shown in FIG. 1 , the flow path of the air ends in the diffuser space 20 when the stem 14 is screwed onto the threaded stem 12 such that the end-face of the stem 14 sealingly bears on the inner side of the component 6 .
[0036] By way of rotation of the handle 30 in a direction B, the component 8 may now be adjusted with respect to the component 6 , such that as shown in FIG. 2 , a gap 32 is formed between the end-face of the stem 14 and the inner side of the component 6 . The gap 32 releases a flow path from the diffuser space 20 to the air guidance channels 24 , so that with this position, a flow path X is created from the ventilation system via recess 22 to the diffuser space 20 and from there via the gap 32 to the air guidance channels 24 and further to the surroundings. Thus the stem 14 together with the inner side of the component 6 form a throttle means whose changeable throttle cross section is formed by the gap 32 . The airflows exiting at the exit openings 36 of the air guidance channels 24 or the air quantity flowing out may be set by way of rotating the handle 30 and thus by way of changing the size of the gap 32 , i.e. of the throttle cross section.
[0037] While specific embodiments of the invention have been shown and described in detail to illustrate the application of the principles of the invention, it will be understood that the invention may be embodied otherwise without departing from such principles.
APPENDIX
[0038] TO ALL WHOM IT MAY CONCERN:
[0039] BE IT KNOWN THAT WE, Rüdiger Meckes of Moorhof 8, D-23919 Berkenthin Federal Republic of Germany, and WOLFGANG RITTNER, of An der Trave 1, D-23623 Siblin, Federal Republic of Germany, both German citizens, have invented certain new and useful improvements in an AIR EXIT GUIDANCE of which the above is a specification.
LIST OF REFERENCE NUMERALS
[0000]
2 flow guidance component
4 mounting- and fastening component
6 first component of 2
8 second component of 2
10 end-side
12 threaded stem
14 stem
16 pocket hole
18 sealing ring
20 diffuser space
22 recesses, air inlet openings
24 air guidance channels
26 air inlet
28 region
30 handle
32 gap
34 sealing ring
36 exit openings
A longitudinal, middle axis
B rotational directions
C pivot directions
X flow path | An air exit guidance which in particular is provided for arrangement in the personal service unit of an passenger aircraft. The guidance includes an air inlet and an air outlet as well as an adjustable throttle which is arranged at the inflow side of the air exit guidance. | 1 |
FIELD OF THE INVENTION
The present invention relates to an organizer system designed to organize a plurality of different items that are very similar in appearance and to provide a user with guidance in identifying a desired one of the plurality of different items. The present invention further relates to a manner of facilitating identification of a desired one of a plurality of different items.
BACKGROUND OF THE INVENTION
Various organizer systems are known in the art for organizing different types of articles in an organizer or other type of holder or container or case. Such organizer systems generally organize the articles according to type, separating one from the other such as within different compartments. For instance, a plurality of similar articles may be placed in each compartment, the articles in one compartment differing from the articles in the other compartment so that the compartments serve to organize the articles by type.
Difficulties arise with organizer systems for articles that are different from each other but which are not readily distinguishable from one another, either because of their appearance or because of their arrangement within the compartments. For instance, existing organizers that separate a plurality of different types of similar-looking articles (different articles that nonetheless are not readily distinguishable from one another) by grouping articles of the same type separately from articles of a different type have not been known to provide a ready means of readily distinguishing the different articles from one another. Thus, even though the user may feel assured that all articles in a given compartment are of a same type, the user may not know what that type of article actually is because such article is not readily distinguishable from an article or articles in other compartments in the organizer system.
Moreover, various packagings are known for containing a plurality of different types of articles that are not readily distinguishable from one another in a manner that does not expose the articles for ready identification. For instance, articles that are not marked along a given side may be arranged with only such unmarked side readily visible. The articles must be individually removed from the packaging and examined to determine the identity of the article. Such packagings have not been known to provide a ready means of distinguishing the different articles from one another without removing the articles and examining the articles. Such problem is exacerbated when the articles are tightly packed in the packaging and need to be pulled out and examined to differentiate one article from the other, possibly disturbing the other articles in the packaging. Even more challenging are packages of different types of articles that do not bear any identifying indicia for differentiating among the different types of articles. One common example is a box of adhesive bandages containing different types of bandages, wherein the wrappers of the bandages do not specify the type of bandage therein. A user not only must remove the bandage from the box, but typically must also hold the bandage up to the light to see through the wrapper to identify the bandage.
Such organizer systems and packagings have existed for many years without having presented a solution to the difficulties thereby presented in differentiating articles that are difficult to differentiate for the above-described reasons. Although it is recognized that boxes for food items may include menus identifying and differentiating the different types of food items contained therein, such menus have not been used for identifying and differentiating consumer items, such as bandages or first-aid supplies. More particularly, menus have not been used to identify and differentiate grouped articles, wherein the articles are not readily differentiable from one another. The present invention addresses the needs for identifying compartmentalized items and for differentiating among a plurality of groups of articles that are not otherwise readily differentiable from one another.
SUMMARY OF THE INVENTION
In accordance with the principles of the present invention, an organizer system is configured for organizing different articles that are not be readily distinguishable from one another so that the user can readily identify and select the desired article from the organizer system. In a preferred embodiment, the different articles are sorted by article type and each group of articles of the same type is stored in a separate compartment to separate the different types of articles from one another. The articles may be organized in an insert or tray that is removable from a shell portion of the container so the shell can be used for other purposes. Further in accordance with the principles of the present invention, a guide or chart or “menu” or other type of article identifying feature (hereinafter “menu” for the sake of convenience, without intent to limit) may be used to readily identify the articles contained in each of the various compartments.
In order to assure that the menu is readily accessible and facilitates selection of the desired article to the greatest extent and ease, the menu may be coupled to the container. In one embodiment, the menu may be provided in the lid of the container. More particularly, if desired, the menu may be formed separately from yet fixedly provided within the lid of the container.
In accordance with another aspect of the present invention, the organizer system may have a container with a hinged or flip-top lid that remains coupled with the holding portion of the container in which the articles are organized. The provision of a menu on the interior-facing surface of such lid is particularly helpful in assuring the menu is always readily accessible and arranged in close conjunction with the articles to be selected with the assistance of the menu.
In accordance with another aspect of the invention, the compartments may be formed by an insert separate from the container of the organizer system. The container may be formed from a sturdier material than that of the insert so that it lasts longer, whereas the material of the insert may be formed from a material that is less expensive yet easier to form into the desired compartments. As such, when the articles contained and/or stored in the organizer system of the present invention have all been used or removed, a new insert containing the same articles as before or different articles may be placed into the container. Alternatively, the container may be used for other purposes without the insert and compartments.
These and other features and advantages of the present invention will be readily apparent from the following detailed description of the invention, the scope of the invention being set out in the appended claims.
BRIEF DESCRIPTION OF THE DRAWINGS
The detailed description will be better understood in conjunction with the accompanying drawings, wherein like reference characters represent like elements, as follows:
FIG. 1 is a perspective view of an organizer system formed in accordance with the principles of the present invention;
FIG. 2 is a top plan view of an organizer system as in FIG. 1 with the lid open and substantially horizontal;
FIG. 3 is an exploded view of an embodiment of an organizer system formed in accordance with the principles of the present invention and in which compartments are formed by providing an insert element within a separately formed container shell, and a menu is formed separately from the container as well; and
FIG. 4 is a top and side perspective view of an exemplary compartment insert showing the compartments formed therein.
FIG. 5 is a top plan view of an alternate embodiment of an organizer system.
DETAILED DESCRIPTION OF THE INVENTION
An exemplary organizer system 100 formed in accordance with the principles of the present invention is illustrated in FIG. 1 . Organizer system 100 includes a container 102 having a base 104 configured for containing and/or storing articles therein, the articles being accessible via open end 106 of base 104 . In accordance with the principles of the present invention, organizer system 100 is particularly designed to organize different articles to be contained and/or stored in base 104 so that a user may readily select the desired one of the various types of articles. In particular, it is preferable that organizer system 100 provide a manner of separating the articles by type for ready selection and removal from containment or storage within base 104 . Accordingly, interior 108 of base 104 preferably is provided with two or more compartments 110 , within each of which a different type of article or group of identical articles may be placed. Such compartments may be separated by dividing walls 112 or by any other element that serves to maintain different articles apart from one another. As will be described in further detail below, organizer system 100 may be formed specifically to contain and/or store articles in a manner that makes identification and differentiation of each article from the other difficult and inconvenient. Such intentional, typically undesirable, configuration may in fact be desirable for such reasons as space efficiency (resulting in cost savings in material as well) or for articles that are not readily distinguishable from one another anyway.
As may be appreciated with reference to FIG. 2 , compartments 110 may include a plurality of different compartments 110 a , 110 b , 110 c , 110 d , 110 e , 110 f , 110 g (collectively, compartments “ 110 ”) formed in various shapes and/or dimensions (either the same or different) and arranged with respect to one another in a preferably neat and organized manner. For instance, compartments 110 may be shaped and/or dimensioned to accommodate the particular shape and/or dimension of the given article to be contained therein. Thus, a compartment such as compartment 110 a may be particularly convenient for an article that is longer than half the width W of base 104 , as compartment 110 a may extend the full width W of base 104 . As may be further appreciated with reference to FIG. 2 , and particularly with reference to exemplary compartments 110 e and 110 f , compartments formed in accordance with the principles of the present invention need not have dividing walls 112 therebetween. Moreover, the relative sizes and/or dimensions of compartments 110 may alternatively or additionally be selected based on the number of articles to be accommodated therein. For instance, compartment 110 g of FIG. 2 may contain articles of essentially the same size as articles contained within any of compartments 110 d , 110 e , or 110 f , but is larger than those compartments to contain more of the given article to be received therein than the number of articles to be received within any of compartments 110 d , 110 e , or 110 f individually. It will be appreciated that the shapes, dimensions, sizes, and relative arrangement of compartments 110 with respect to one another is in no way limited by the illustrative arrangement in FIG. 2 , such arrangement being merely one example of an arrangement of exemplary shaped and dimensioned and sized compartments 110 .
Compartments 110 may be formed in any desired manner within base 104 . For instance, compartment walls 112 may be formed integrally with base 104 , such as by molding ribs or dividers into base 104 as a monolithic part of base 104 . However, to enhance versatility of organizer system 100 , compartments 110 may be formed as a separable, removable element insertable within a main “shell” portion of container 102 . For instance, a separate wall structure may be insertable into and readily removable from base 104 to form compartments 110 as desired. A wall structure separate from base 104 may be in any desired form, such as a grid formed from paperboard or cardboard (such as used to separate breakable bottles from one another in a carton). Alternatively, exemplary insert 120 of FIGS. 3 and 4 may provide compartments 110 as separate parts selectively insertable into and removable from base 104 . Insert 120 may be in the form of a shell in which walls 112 of compartments 110 are formed and which may be separable and removable from base. A separately formed shell 120 providing interchangeability of compartments 110 provides an added benefit of permitting ready refilling of base 104 with another newly filled insert 120 , or a different insert (such as containing and/or storing different articles or having differently shaped compartments), and/or use of base 104 without any compartments therein (such as for purposes other than storing articles in separate compartments).
Additionally, if compartments 110 are formed separately from base 104 of container 102 (such as in the form of separable walls 112 or a separate insert 120 ), then the material of container 102 need not be the same as the material of walls 112 and/or compartments 110 and/or may be formed using a different manufacturing method. For instance, base 104 may be formed from a durable material (to permit extended use of container 102 even after all articles contained and/or stored therein have been removed and/or expended). Materials that may be used to form container 102 and base 104 include, without limitation, polypropylene and acrylonitrile butadiene styrene (ABS) resins, selection being determined on any of a variety of factors such as durability, rigidity, cost, etc. It will be appreciated that the present invention is not limited to a particular method for manufacturing container 102 , and any desirable method (such as injection molding) may be used. Provision of compartments 110 via a separate insert 120 permits a less expensive material and/or method of manufacturing to be used for insert 120 , which may be particularly desirable if insert 120 is to be replaced while container 102 is to be reused. For instance, in one embodiment, insert 120 may be formed of a high impact polystyrene (HIPS) that is thermoformed into the desired shape. Of course, other materials and other methods of manufacturing (such as injection molding) may be used instead without affecting the scope of the present invention.
Referring again to FIGS. 1-3 , container 102 may be provided with a lid 130 , if desired, such as to protect articles contained and/or stored within base 104 , and/or to maintain the articles within container 102 . Lid 130 preferably is configured to fit over and to close open end 106 of base 104 . Although lid 130 is shown to conform to the cross-sectional shape of base 104 (as may be appreciated particularly with reference to FIG. 2 ), such conforming shape is not necessary.
Lid 130 may be fixedly coupled to base 104 of container 102 so that lid 130 remains with base 104 during the use and life of organizer system 100 . For instance, the exemplary lid 130 of FIGS. 1-3 is hingedly coupled to base 104 . In particular, a living hinge couples lid 130 and base 104 together (so that lid 130 and base 104 may be molded as a single piece). However, it will be appreciated that any other manner of coupling lid 130 and base 104 may be used. It will further be appreciated that even though exemplary lid 130 is illustrated as coupled to base 104 of container 102 , lid 130 may be formed as a separate element that is completely removal from base 104 without any steps such as severing a connection therebetween.
If desired, lid 130 may be formed with alignment elements to assist in aligning and/or maintaining lid 130 over open end 106 of base 104 . For instance, a raised surface or rib 132 may be provided on one of lid 130 and base 104 to fit into a recess 134 on the other of lid 130 and base 104 . As may be appreciated, such rib and recess combination assures a particular alignment when used. Moreover, such rib and recess combination may impart a greater degree of friction between lid 130 and base 104 , thereby maintaining lid 130 on base 104 in a closed configuration.
If articles are to be contained and/or stored within organizer system 100 in an airtight manner, a seal may be formed to interact with lid and main body of container. Such seal may be formed in any desired manner known in the art, the precise embodiment not affecting the scope of the present invention. The interaction of rib 132 with recess 134 described above may suffice, or addition of further sealing elements may be appropriate, as would be within the ken of one of ordinary skill in the art.
If desired, lid 130 may be formed with a closing mechanism that functions to maintain lid 130 in a closed position covering open end 106 of base 104 of container 102 . For instance, a latch may be provided in any of a variety of manners known to those of ordinary skill in the art. In the exemplary embodiment of FIGS. 1-3 , a detent 136 and mating recess 138 may be provided on lid 130 and base 104 to interact with each other as an internal hinge that maintains lid 130 closed over open end 106 of base 104 . Although detent 136 may be provided on either one of lid 130 and base 104 and recess 138 may be provided on the other of lid 130 and base 104 , if detent 136 is provided on base 104 , and base 104 is formed of a relatively flexible material, then lid 130 may be opened by pressing on base wall 105 on which detent 136 is provided to release detent 136 from recess 138 .
In accordance with the principles of the present invention, organizer system 100 is designed to address the unique disadvantages resulting from a plurality of different articles either being organized in a manner that interferes with ready differentiation of the articles, or being formed so that ready differentiation of the articles from one another is difficult, such as illustrated in the exemplary embodiment of FIG. 5 . Specifically, articles 200 are arranged closely together in container 102 in a manner that does not permit ready identification of any individual article. The present invention intentionally disregards the disadvantages of such arrangement of articles 200 by providing a solution for readily identifying the articles despite such arrangement. In the exemplary embodiment of FIG. 14 , organizer system 100 includes (1) a container 102 that preferably is particularly designed to contain and/or store different types of articles in a manner that does not permit ready identification of a particular desired article, and (2) a guide, such as menu 140 , in conjunction with container 102 configured to assist a user in selecting a particular desired article from container 102 . More particularly, although it is acknowledged that it is known to provide organizer systems for separating similar articles that are not identical to each other into compartments for each of the different types of articles, such separation still does not on its own assist the user in identifying the desired article. Moreover, the illustrated embodiment of the present invention is configured intentionally to organize articles in an efficient, space-saving manner that has the disadvantage of making identification of each article inconvenient and difficult. Because of such configuration, organizer system 100 of the present invention is particularly well-suited for storing a variety of articles that either do not have any identifying or differentiating indicia on them (such adhesive bandages, gauze pads, or sanitary napkins, which typically have wrappers that do not identify the type of adhesive bandage or sanitary napkin therein), or do not have a surface with identifying indicia exposed to the user while the article is stored within container 102 (such as pain relievers or other medications in bottles with caps or lids that look similar when viewed from above; or stationery goods such as labels; or tea bags stacked on their ends). The latter types of articles generally are stacked edgewise, or in a manner presenting a side smaller in dimension than the other sides of the article and thus not amenable to bearing identifying indicia. Such articles may be tightly packed and must be individually drawn out of interior 106 of base 104 to be identified. The present invention is particularly designed for storing such articles and for providing a menu 140 that heretofore has not been provided in conjunction with such articles stored in such manner. Menu 140 facilitates ready selection of a desired one of a plurality of different types of articles without the need to remove and/or to examine the article.
Given the nature of the articles for which organizer system 100 is particularly suited, no pictures are necessary on the menu since a picture likely will not provide useful information in any event. However, if desired, menu 140 may be configured to have regions corresponding (such as in shape and/or relative position) to compartments 110 , thus potentially further facilitating use of menu 140 in identifying a desired article.
It is helpful to maintain such an uncommon menu (in that no pictures of the articles identified by the menu is provided) in a particular orientation to facilitate matching of items on the menu with articles within container 102 , and particularly within the individual compartments 110 therein. To further facilitate use, menu 140 may be coupled to organizer system 100 . In the embodiment illustrated in FIGS. 1 and 2 , menu 140 may be coupled to container 102 to remain therewith in a particular orientation. Such positioning is in contrast with menus, such as used in boxes of chocolate, that are separate inserts provided within the box. Coupling of menu 140 with container 102 may be achieved in any of a desired number of manners, such as via lid 130 (lid 130 in turn being coupled to base 104 of container 102 either fixedly or removably), or by being fixed directly to base 104 (such as by being adhered to wall 105 of base 104 , such as if a lid is not provided). As such, menu 140 is always readily available for reference purposes.
As a further feature of coupling menu 140 to container 102 via a fixedly coupled lid 130 , lid 130 may be provided in a manner that permits lid 130 to maintain itself in an open position. The manner of coupling lid 130 to base 104 may achieve such function in a variety of manners. For instance, a hinge that can maintain lid 130 in a fixed open position may be used. If a living hinge is used, such as living hinge 131 of FIGS. 1-3 , then the material thereof may be selected to permit selective positioning and maintenance of the selected positioning (such as by virtue of a degree of memory in the material). One such material that permits repositioning of a living hinge is polypropylene, although other materials may be used in the present invention instead. Accordingly, lid 130 remains open on its own without the necessity of the user actively holding lid 130 open. A user thus may readily peruse menu 130 and select an article without worrying if lid 130 will close on its own.
It will be appreciated that menu 140 may be formed in any desired manner with respect to container 102 . In the illustrated embodiment of FIG. 3 , menu 140 is formed as a separate element that may then be secured to the interior surface 133 of lid 130 . An economical and efficient manner of forming a menu as an element separate from container 102 is by printing the graphics of menu 130 on paperboard (or another suitable material) and coupling menu 130 to interior surface 133 of lid 130 . Coupling may be achieved in any desired manner, such as by permanent adhesive, releasable adhesive, tape, etc. If replacement of insert 120 of the embodiment of FIG. 3 is desirable, then releasable adhesive gives the added benefit of ready removal and replacement of menu 140 with another menu that corresponds to the replacement insert and the articles contained therein. Other manners of forming menu 140 are well within the scope of the present invention. For instance, the menu may be embossed, printed, and/or molded (using any know manner of embossing, imprinting, or molding) within interior surface 133 of lid 130 , thus forming an integral part of lid 130 .
If a lid is not necessary for container 102 , it will be appreciated that the menu may be provided on a wall of container 102 so that the menu is readily available for reference purposes to assist a user in selecting a desired article from within base 104 . For instance, a menu may be provided on wall 105 of base 104 arranged to facilitate use of the menu in identifying a desired article within base 104 .
In accordance with another aspect of the present invention, container 102 may be coupled to another container such as by means of coupling elements 150 as illustrated in the exemplary embodiment of FIG. 3 . Coupling elements 150 may be formed in any desired manner to provide selective coupling and decoupling of containers together and apart from each other. The exemplary illustrated coupling elements 150 are formed by providing angularly outwardly extending wings on one side of the container (as illustrated in FIG. 3 ) and angularly inwardly extending wings on the other side. The angularly outwardly extending wings of one container interengage with the angularly inwardly extending wings of another container by moving the containers with respect to each other in a vertical direction. If desired, a stop wall may be provided so that once two containers are coupled together, the stop wall prevents the containers from sliding apart from each other.
While the foregoing description and drawings represent exemplary embodiments of the present invention, it will be understood that various additions, modifications and substitutions may be made therein without departing from the spirit and scope of the present invention. In particular, it will be clear to those skilled in the art that the present invention may be embodied in other specific forms, structures, arrangements, proportions, and with other elements, materials, and components, without departing from the spirit or essential characteristics thereof. For instance, the shape and dimensions of the exemplary container shown in the FIGURES are illustrative only. Moreover, various modifications to the lid, such as manners of coupling the lid to the main body of the container, or the manner of maintaining the lid in the closed position, are within the scope of the present invention. It will be appreciated that the shape and dimensions of any of the elements of the present invention may be modified in any desired manner, such as to accommodate differently sized or shaped articles. One skilled in the art will appreciate that the invention may be used with many modifications of structure, arrangement, proportions, materials, and components and otherwise, used in the practice of the invention, which are particularly adapted to specific environments and operative requirements without departing from the principles of the present invention. For example, elements shown as integrally formed may be constructed of multiple parts or elements shown as multiple parts may be integrally formed, the operation of elements may be reversed or otherwise varied, the size or dimensions of the elements may be varied. The presently disclosed embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims, and not limited to the foregoing description. | A system for organizing very similar articles in a container so that the user can readily identify the desired article. A “menu” may be used to readily identify the articles, which preferably are non-food, consumer items, such as bandages or first-aid supplies. The “menu” may be provided in the lid of the container. If desired, the “menu” may be fixedly provided in the lid of the container, such as on the interior-facing surface of a flip-top or hinged-lid of the container. The articles may be organized in an insert or tray that is removable from a shell portion of the container so the shell can be used for other purposes. | 1 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to driver handles for interchangeable driver bits and, in particular, to handles of the ratcheting type.
2. Description of the Prior Art
Ratcheting drivers have heretofore been provided, as have drivers with interchangeable bits. One type of ratcheting driver for interchangeable bits is disclosed in U.S. Pat. No. 4,777,852. That patent discloses a ratcheting arrangement wherein a ratchet body is press-fitted into a recess in one end of a handle and a cap telescopes over the body for rotation with respect thereto. A fairly complex linkage mechanism transmits force from the rotating cap to a pair of pawls for controlling engagement thereof with a ratchet gear, in which one end of a shank is coaxially received. The force transmission from the cap to the pawl assembly is indirect and involves a multi-part assembly.
SUMMARY OF THE INVENTION
It is a general object of the invention to provide an improved ratcheting driver handle which avoids the disadvantages of prior driver handles while affording additional structural and operating advantages.
An important feature of the invention is the provision of a ratcheting driver handle of the type set forth, which is of relatively simple and economical construction.
In connection with the foregoing feature, another feature of the invention is the provision of a handle of the type set forth which provides direct coupling between a selector and the pawl assembly of a ratcheting mechanism.
Another feature of the invention is the provision of a handle of the type set forth, which effectively retains the selector in either of selected forward or reverse positions, while at the same time effectively preventing overtravel of the selector.
Still another feature of the invention is the provision of an effective means for coupling an interchangeable bit with the driver handle.
These and other features of the invention are attained by providing a ratcheting driver handle for a driver bit having a shank, the handle comprising: an elongated body having an axis and an axial recess in one end thereof, ratchet mechanism disposed in the recess and including a gear and a pawl assembly engageable with the gear, the ratchet mechanism defining a bore for receiving the shank of the associated bit therein, the pawl assembly being movable between first and second conditions, the pawl assembly in its first condition engaging the gear so that the body rotates the gear therewith in one direction and ratchets with respect to the gear in the opposite direction, the pawl assembly in its second condition engaging the gear so that the body rotates the gear therewith in the opposite direction and ratchets with respect to the gear in the one direction, an annular selector member coupled to the one end of the body for rotation with respect thereto about the axis thereof between first and second positions respectively corresponding to the first and second conditions, an actuator carried by the selector member and engageable with the pawl assembly for movement thereof between the first and second conditions thereof in response to rotation of the selector member between the first and second positions thereof, and bias mechanism resiliently retaining the selector member in each of the first and second positions.
The invention consists of certain novel features and a combination of parts hereinafter fully described, illustrated in the accompanying drawings, and particularly pointed out in the appended claims, it being understood that various changes in the details may be made without departing from the spirit, or sacrificing any of the advantages of the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
For the purpose of facilitating an understanding of the invention, there is illustrated in the accompanying drawings a preferred embodiment thereof, from an inspection of which, when considered in connection with the following description, the invention, its construction and operation, and many of its advantages should be readily understood and appreciated.
FIG. 1 is a perspective view of a ratcheting driver handle constructed in accordance with the present invention, with a screwdriver bit mounted therein;
FIG. 2 is a slightly reduced, exploded, perspective view of the handle/bit combination shown in FIG. 1;
FIG. 3 is an enlarged, side elevational view of the handle of FIG. 1 in partial vertical section, illustrating the ratcheting mechanism; and
FIG. 4 is a view in vertical section taken along the line 4--4 in FIG. 3.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to FIGS. 1-3, there is illustrated a driver handle, generally designated by the numeral 10, which includes an elongated body 11 having an outer surface 12 sculpted to provide a good grip for the hand of the user. The body 11 has a flat, circular end wall 13 at one end thereof in which is formed an axial bore 14 (see FIG. 3) having successively increasing-diameter counterbores 16 and 17.
Referring in particular to FIGS. 2-4, the handle 10 is provided with a ratchet housing 20 having an elongated shank 21 adapted to be press-fitted in the bore 14. More specifically, the shank 21 is provided with a plurality of radially outwardly extending splines 22 to be received in the bore 14, effectively to prevent rotational movement of the housing 20 about the axis of the handle 10. The housing 20 has an enlarged-diameter portion 23 adapted to fit mateably in the counterbore 16 when the shank 21 is inserted in the bore 14. Adjacent to the enlarged-diameter portion 23 is a shoulder portion 24 having a still greater diameter, and adapted to fit in the counterbore 17. Unitary with the shoulder portion 24 is an enlarged-diameter cylindrical head 25, having a cylindrical outer surface 26 provided adjacent to the rear end thereof with a radially outwardly extending circumferential rib 27. In use, the shank 21 of the housing 20 is inserted in the bore 14 until the rear end of the head 25 abuts the end wall 13 of the body 11, as can best be seen in FIG. 3.
The head 25 has an end face 29, in which is formed a socket 30. The socket 30 includes a cylindrical bore 31 extending axially into the housing 20 and, specifically, well into the enlarged-diameter portion 23 thereof. The socket 30 has an enlarged-diameter cylindrical counterbore 32, which extends slightly into the shoulder portion 24, and upper and lower pockets 33 and 35 which communicate with the counterbore 32. The upper pocket 33 is substantially rectangular in shape and intersects the upper portion of the counterbore 32 and extends laterally outwardly therebeyond. The lower pocket 35 intersects the lower portion of the counterbore 32 and is provided with a pair of laterally outwardly extending slots 36.
A ratchet mechanism 40 is disposed in the socket 30. More specifically, the ratchet mechanism 40 includes a cylindrical gear 41 having an axial bore 42 therethrough, the bore 42 being oblong in transverse cross section, viz., essentially in the form of a cylindrical bore with truncated flat sides 43 defining chords of the cylinder. A cylindrical counterbore 44 is formed in the rear face of the gear 41 for receiving a split retaining ring 45, which has an inner diameter less than that of the bore 42. The gear 41 has teeth 47 around the outer surface thereof and is dimensioned to be seated in the counterbore 32 of the socket 30 for free rotational movement coaxially therewith. A thrust washer 46 may be disposed in the counterbore 32 behind the gear 41 for wear resistance. Preferably, the arcuate portion of the bore 42 has a diameter substantially equal to that of the bore 31 of the socket 30. An elongated, slightly arcuate leaf spring 48 has the opposite ends thereof respectively seated in the slots 36, with the spring 48 bowed upwardly, as can best be seen in FIG. 4.
The ratchet mechanism 40 also includes a pawl assembly including a pair of pawls 50 and 50A, respectively disposed in opposite ends of the upper pocket 33 of the socket 30, and formed as mirror images of each other. Each of the pawls 50 and 50A has a tooth 51 disposed for meshing engagement with the teeth 47 of the gear 41. Each also has a finger 52 having a recess 55 in the front side thereof, the fingers 52 being directed toward each other. The outer ends of the pawls 50 and 50A are provided with cylindrical bores 53, in which are respectively seated helical compression springs 54, which respectively bear against the adjacent ends of the upper pocket 33 resiliently to urge the pawls 50 and 50A into engagement with the gear 41, as can best be seen in FIG. 4.
In operation, when both of the pawls 50 and 50A are disposed in engagement with the gear 41, the gear 41 is locked against rotation relative to the handle 10. If the pawl 50A is pushed back out of engagement with the gear 41 against the urging of the associated spring 54, as illustrated in FIG. 4, so that only the pawl 50 engages the gear 41, then the gear 41 is adapted for ratcheting rotation in the direction of the arrow in FIG. 4 relative to the handle 10 and is locked against rotation in the opposite direction. It will be appreciated that the opposite is true if only the pawl 50A engages the gear 41.
The handle 10 also includes a selector cap 60 which is generally cup-shaped, including a generally circular end wall 61 integral around the periphery thereof with a cylindrical side wall 62. The end wall 61 has a cylindrical axial bore 63 extending therethrough which has substantially the same diameter as the bore 31 of the socket 30. Projecting laterally inwardly from the side wall 62 adjacent to the distal end thereof and around the entire circumference thereof is a retaining lip 64 (see FIG. 3). In use, the side wall 62 is dimensioned to be fitted telescopically over the head 25 of the ratchet housing 20 for free rotation relative thereto about the axis thereof, the retaining lip 64 snap-fitting over the circumferential rib 27 on the head 25 to prevent axial movement of the cap 60 once it has been installed in place.
Preferably, the cap 60 is formed of a suitable plastic material and has therein two pins 65 and 66 at diametrically opposed locations thereon, the pins 65 and 66 respectively projecting axially rearwardly of the end wall 61 predetermined distances, but substantially less than the axial extent of the side wall 62. The pins 65 and 66 are spaced apart a distance such that, when the cap 60 is installed in place, as illustrated in FIGS. 3 and 4, the pins 65 and 66 will both be disposed radially just outboard of the periphery of the gear 41. The pin 65 fits between the pawls 50 and 50A in the recesses 55 thereof, while the pin 66 is disposed in the lower pocket 35 of the socket 30 for engagement with the leaf spring 48. Preferably, the sidewall 62 of the cap 60 is provided on its outer surface with an indicium 67, to cooperate with corresponding indicia 68 on the handle 10 for indicating whether the selector cap 60 is in the forward or reverse position.
As can be seen from FIG. 4, in one of those positions, the pin 65 will hold the pawl 50A out of engagement with gear 41, while the pin 66 is seated against one side of the lower pocket 35, being resiliently urged to that position by the leaf spring 48. Thus, the gear 41 can ratchet in only one direction, which may be considered the forward direction. When the selector cap 60 is rotated clockwise, as viewed in FIGS. 1 and 4, from the position illustrated in FIG. 4 to the reverse position, the pin 65 will hold pawl 50 out of engagement with the gear 41. In order to move to this position, the pin 66 must overcome the bias of the leaf spring 48, flattening its bow sufficiently to move over center, this rotational movement of the cap 60 being stopped by engagement of the pin 66 with the other side of the lower pocket 35. Thus, it will be appreciated that the leaf spring 48 serves to resiliently retain the selector cap 60 in either of the forward or reverse positions in which it happens to be located and inhibits movement from that position, while the cooperation of the pin 66 with the sides of the lower pocket 35 effectively prevents overrotation of the selector cap 60.
Referring in particular to FIGS. 1 and 2, there is illustrated a driver bit 70 having an elongated cylindrical shank 71, provided at one end thereof with a blade 72 which, in the illustrated embodiment, is a slot-head screwdriver blade. The shank 71 is provided adjacent to the other end thereof with an enlarged-diameter portion 73, which terminates in a flat end 75 having parallel flat side surfaces 76 which lie along chords of the enlarged-diameter part 73. It will be appreciated that the enlarged-diameter portion 73 has a diameter slightly less than that of the bores 31 and 63 of the socket 30 and selector cap 60, respectively. Also, the flat end 75 is shaped and dimensioned for mateably being received in the bore 42 of the gear 41, cooperating therewith to prevent rotation of the bit 70 with respect to the gear 41. In this regard, the arcuate side edges of the flat end 75 are preferably chamfered, as at 77, to facilitate insertion in the bore 42 and through the retaining ring 45. It will be appreciated that the retaining ring 45 frictionally engages the arcuate portions of the flat end 75 for frictionally retaining the bit shank 71 in place in the handle 10. Accordingly, the bit 70 will rotate with the gear 41, in a known manner, the frictional retention of the bit 70 permitting removal of the bit 70 for interchange with other bits. It will also be appreciated that the shoulders formed between the flat end 75 and the enlarged-diameter portion 73 of the bit 70 engage the front surface of the gear 41 to limit the depth of insertion therein.
From the foregoing, it can be seen that there has been provided an improved ratcheting driver handle which is of simple and economical construction, affording a direct actuation of the ratchet mechanism pawls between forward and reverse directions, and yieldably retaining the mechanism in each of the forward and reverse directions while effectively preventing overtravel of the direction selector. The handle also affords a simple and easy easily releasable coupling to associated driver bits. | A ratcheting driver handle has a ratchet body press-fitted axially in one end thereof, the body defining a socket which receives a gear for rotation coaxially with the handle. The socket also receives two pawls respectively disposed above and at opposite sides of the axis and spring-biased into engagement with the gear. A selector cap rotates on the housing and carries a first pin for driving the pawls respectively out of engagement with the gear, depending upon the direction of rotation, to control the ratchet direction. A second pin on the cap engages an over-center leaf spring mounted in the socket below the gear for resiliently retaining the mechanism in either of the forward or reverse conditions. A driver bit has a flattened end which is received through an axial bore in the cap and into a complementarily shaped bore through the gear for rotation therewith, being frictionally retained in place by a retaining ring. | 1 |
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation-in-part of U.S. patent application Ser. No. 12/127,544, filed May 27, 2008, which is assigned to the assignee of the present patent application and whose disclosure is incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates generally to methods and systems for medical diagnostic imaging, and specifically to radio frequency (RF)-based imaging.
BACKGROUND OF THE INVENTION
[0003] Narrowing of the coronary arteries due to atherosclerosis is commonly treated by implantation of a stent, using a catheter, to hold the artery open. In a large fraction of cases, however, the treated artery closes up again due to in-stent restenosis, necessitating further treatment. Accurate assessment of such restenosis generally requires re-catheterization. A number of non-invasive techniques have been proposed, such as in U.S. Pat. No. 6,729,336, in which an electromagnetic wave transmitter is used to excite a stent, and an acoustic sensor detects stent acoustic oscillations.
[0004] RF imaging is best known in the context of radar systems, but RF diagnostic imaging systems have also been developed for medical applications. For example, U.S. Patent Application Publication 2008/0169961, whose disclosure is incorporated herein by reference, describes computerized tomography using radar, which may be used for generating an image of living tissue. As another example, U.S. Pat. No. 7,454,242, whose disclosure is incorporated herein by reference, describes tissue-sensing adaptive radar imaging for breast tumor detection.
[0005] Various antenna designs have been proposed for RF imaging of body tissues. For example, U.S. Pat. No. 6,061,589, whose disclosure is incorporated herein by reference, describes a microwave antenna for use in a system for detecting an incipient tumor in living tissue, such as that of a human breast, in accordance with differences in relative dielectric characteristics. A composite Maltese Cross or bow-tie antenna construction is employed to irradiate the living tissue and to collect backscatter or other scatter returns.
SUMMARY
[0006] Embodiments of the present invention that are described hereinbelow provide improved devices and methods for detecting features inside a living body using RF imaging techniques. Although some of these embodiments are directed specifically to detection of features in the heart, and specifically in the coronary arteries, the principles of these embodiments may similarly be applied in imaging, detection and tracking of features elsewhere in the body.
[0007] There is therefore provided, in accordance with an embodiment of the present invention, diagnostic apparatus, including an antenna, which is configured to direct radio frequency (RF) electromagnetic waves into a living body and to generate signals responsively to the waves that are scattered from within the body. Processing circuitry is configured to process the signals so as to locate a feature in a blood vessel in the body.
[0008] In disclosed embodiments, the apparatus includes an ultrasound transducer, and the processing circuitry is configured to guide the ultrasound transducer to direct an ultrasonic beam toward the feature. In one embodiment, the feature located by the processing circuitry includes a stent, and the ultrasound transducer is configured to generate a Doppler signal responsively to a flow of blood through the stent.
[0009] Additionally or alternatively, the apparatus includes a tracking unit, which is configured to track respective coordinates of the antenna and of the ultrasound transducer, and the processing circuitry is configured to guide the ultrasound transducer responsively to the respective coordinates. The apparatus typically includes position transducers fixed respectively to the ultrasound transducer and to the antenna, wherein the tracking unit is configured to track the respective coordinates responsively to position signals exchanged between the position transducers and the tracking system.
[0010] Further additionally or alternatively, the apparatus includes a display, wherein the processing circuitry is configured to guide the ultrasound transducer by driving the display to present to an operator of the ultrasound transducer an indication of a direction in which the ultrasound transducer should be aimed.
[0011] In a disclosed embodiment, the blood vessel is a coronary artery. The processing circuitry may be configured to track a cyclical motion of the feature over multiple cycles of the heart.
[0012] Typically, the processing circuitry is configured to locate the feature responsively to a difference in a dielectric constant of the feature relative to surrounding tissue.
[0013] There is also provided, in accordance with an embodiment of the present invention, diagnostic apparatus, including an antenna, having a front surface configured to brought into contact with an outer surface of a living body so as to direct radio frequency (RF) electromagnetic waves into the body and to generate signals responsively to the waves that are scattered from within the body. A dielectric gel is adapted to be spread between the outer surface of the body and the front surface of the antenna. Processing circuitry is configured to process the signals so as to locate a feature in the body.
[0014] Typically, the body has a first dielectric constant, and the gel has a second dielectric constant that is chosen to match the first dielectric constant. In disclosed embodiments, the gel has a dielectric constant that is between 30 and 75. The gel may be adhesive.
[0015] In one embodiment, the gel is water-based and includes an additive selected from a group of additives consisting of an alcohol, a salt, a sugar, and glycerin. Alternatively, the gel includes silicone and an additive having a dielectric constant greater than 70.
[0016] There is additionally provided, in accordance with an embodiment of the present invention, diagnostic apparatus, including an antenna, which has a front surface and is configured to direct radio frequency (RF) electromagnetic waves from the front surface into a living body and to generate signals responsively to the waves that are scattered from within the body, and which includes an array of antenna elements, each antenna element including a planar element at the front surface of the antenna and a cavity behind the planar element. Processing circuitry is configured to process the signals so as to locate a feature in the body.
[0017] In disclosed embodiments, the front surface of the antenna includes a printed circuit board, and the planar element of each antenna element includes a conductive radiator printed on the printed circuit board. The printed circuit board may include multiple conductive vias surrounding the radiator for isolating the antenna elements from one another.
[0018] There is further provided, in accordance with an embodiment of the present invention, diagnostic apparatus, including an antenna, including an array of antenna elements, which are configured to direct radio frequency (RF) electromagnetic waves into a living body and to generate signals responsively to the waves that are scattered from within the body. Excitation circuitry is coupled to apply a RF excitation waveform at multiple different frequencies to different transmitting antenna elements, selected from the array, according to a predetermined temporal pattern. Processing circuitry is coupled to receive the signals from different receiving antenna elements, selected from the array, and to process the signals at the different frequencies due to the different transmitting and receiving antenna elements so as to locate a feature in the body.
[0019] In some embodiments, the excitation circuitry includes a driver circuit, which is configured to generate the RF excitation waveform with a variable frequency, and a switching matrix, which is configured to select sets of the antenna elements in alternation, each set including at least one transmitting antenna element and one receiving antenna element, and for each selected set, to couple the driver circuit to excite the at least one transmitting antenna element at a selected frequency while coupling the processing circuitry to receive the signals from the at least one receiving antenna element. In a disclosed embodiment, the driver circuit and the switching matrix are coupled to select pairs of one transmitting antenna element and one receiving antenna element, and to excite the transmitting antenna in each pair at each of a plurality of frequencies in accordance with the predetermined temporal pattern.
[0020] In some embodiments, the apparatus includes a signal conditioning unit, which is configured to cancel a background component of the signals that arises from direct coupling between the transmitting and receiving antenna elements before the processing circuitry receives the signals. The signal conditioning unit may include an amplitude and phase modulator, which is coupled to receive the RF excitation waveform from the driver circuit, to modify a phase and amplitude of the received waveform so as to generate an anti-phased signal matching the background component, and to add the anti-phased signal to a signal received from the at least one receiving antenna element in order to cancel the background component.
[0021] In disclosed embodiments, the processing circuitry is configured to transform the signals received at the different frequencies due to the different transmitting and receiving antenna elements into a three-dimensional (3D) image, and to process the 3D image in order to find a location of the feature. In one embodiment, the processing circuitry is configured to compute a weighted sum of the signals received at the different frequencies due to the different transmitting and receiving antenna elements, using respective weights provided for a plurality of voxels in the 3D image, to determine values of the voxels in the 3D image.
[0022] There is moreover provided, in accordance with an embodiment of the present invention, a method for diagnosis, including directing radio frequency (RF) electromagnetic waves into a living body and generating signals responsively to the waves that are scattered from within the body. The signals are processed so as to locate a feature in a blood vessel in the body.
[0023] There is furthermore provided, in accordance with an embodiment of the present invention, a method for diagnosis, including spreading a dielectric gel between an outer surface of a living body and a front surface of an antenna. The front surface of the antenna is brought into contact, via the dielectric gel, with the outer surface of the living body so as to direct radio frequency (RF) electromagnetic waves into the body and to generate signals in the antenna responsively to the waves that are scattered from within the body. The signals are processed so as to locate a feature in the body.
[0024] There is also provided, in accordance with an embodiment of the present invention, a method for diagnosis, including providing an antenna, which has a front surface and which includes an array of antenna elements, each antenna element including a planar element at the front surface of the antenna and a cavity behind the planar element. Radio frequency (RF) electromagnetic waves are directed from the antenna elements via the front surface of the antenna into a living body and generating signals, using the antenna elements, responsively to the waves that are scattered from within the body. The signals are processed so as to locate a feature in the body.
[0025] There is additionally provided, in accordance with an embodiment of the present invention, a method for diagnosis, including defining a temporal pattern specifying a sequence of multiple different frequencies and spatial channels associated with an array of antenna elements. Radio frequency (RF) electromagnetic waves are directed at the multiple different frequencies into a living body from multiple different transmitting antenna elements that are selected from the array in accordance with the temporal pattern. Signals are generated responsively to the waves that are scattered from within the body and are received at multiple different receiving antenna elements that are selected from the array in accordance with the temporal pattern. The signals from the different receiving antenna elements at the different frequencies are processed so as to locate a feature in the body.
[0026] The present invention will be more fully understood from the following detailed description of the embodiments thereof, taken together with the drawings in which:
BRIEF DESCRIPTION OF THE DRAWINGS
[0027] FIG. 1 is a schematic, pictorial illustration of a system for tracking and assessment of a feature in a human body, in accordance with an embodiment of the present invention;
[0028] FIG. 2 is a block diagram that schematically shows elements of a system for tracking and assessment of a feature in a human body, in accordance with an embodiment of the present invention;
[0029] FIG. 3 is a schematic, pictorial illustration of an antenna array, in accordance with an embodiment of the present invention;
[0030] FIG. 4 is a schematic, exploded view of an antenna element, in accordance with an embodiment of the present invention;
[0031] FIG. 5 is a block diagram that schematically illustrates a feature detection subsystem, in accordance with an embodiment of the present invention;
[0032] FIG. 6 is a timing diagram that schematically illustrates an excitation pattern that is applied to an antenna array, in accordance with an embodiment of the present invention; and
[0033] FIG. 7 is a flow chart that schematically illustrates a method for measuring blood flow through a stent, in accordance with an embodiment of the present invention.
DETAILED DESCRIPTION OF EMBODIMENTS
Overview
[0034] Embodiments of the present invention that are described hereinbelow use radar imaging techniques to identify and locate features in the body. Features are thus identified based on the difference in their complex dielectric constant (referring to both permittivity and conductivity) relative to the dielectric constant of the surrounding tissue. These techniques are particularly useful in detecting and tracking metal objects in the body, but they may also be used to locate features of other kinds, including both introduced objects, such as plastic objects, and naturally-occurring features, such as calcifications, and even pockets of air or other gases. The term “feature,” as used in the context of the present patent application and in the claims, should therefore be understood as referring to any item or location in the body having a distinct dielectric constant.
[0035] Some embodiments of the present invention are directed to locating features in the heart, and particularly in the coronary blood vessels. In these embodiments, an antenna directs RF electromagnetic waves toward the heart and receives the waves that are scattered from within the body. Processing circuitry processes the signals generated by the antenna due to the received waves in order to locate the feature or features of interest, and possibly to track the movement of such features over the course of the heart cycle.
[0036] The radar-based location of a feature may be used in guiding the beam of an ultrasound transducer toward the feature. In one such embodiment, the antenna and processing circuitry find the location of a stent in an artery and guide the ultrasound transducer to direct its beam toward the stent. The ultrasound transducer may operate in Doppler mode in order to measure the flow of blood through the stent and thus non-invasively assess possible restenosis in the stent.
[0037] In the embodiments that are described hereinbelow, the antenna comprises an array of antenna elements, with a front surface that is brought into contact with the outer surface (i.e., the skin) of the patient's body. A dielectric gel may be spread between the body surface and the front surface of the antenna in order to match the dielectric constants and thus improve the penetration of the RF waves into the body. Additionally or alternatively, the antenna elements may comprise a cavity and possibly other features to enhance the efficiency of coupling of electromagnetic energy from the antenna elements into the body while reducing loss and crosstalk between the elements.
[0038] In the disclosed embodiments, excitation circuitry applies a RF excitation waveform at multiple different frequencies to different transmitting antenna elements in the array. Meanwhile, the processing circuitry receives signals from different receiving antenna elements. The selection of transmitting and receiving antennas, as well as the selection of excitation frequency, follows a predetermined temporal pattern, which may be implemented by a switching matrix connected to the antenna elements.
[0039] As a result of this scheme of excitation and reception, the processing circuitry receives and processes signals from multiple spatial channels (corresponding to different pairs of antennas) at multiple different frequencies for each channel. Taken together in the time domain, these multi-frequency signals are equivalent to short pulses of RF energy. To reconstruct a three-dimensional (3D) image of the interior of the body and find the location of a feature or features, the processing circuitry applies a spatial transform to the set of received signals. The transform may, for example, comprise an inverse spherical Radon transform or an algebraic approximation of such a transform.
[0040] Despite measures that are taken to reduce coupling between antenna elements within the array, this sort of direct coupling still generates a strong background component, which tends to mask the signals due to scattered waves from the body. (The term “direct coupling,” as used in the context of the present patent application and in the claims, refers to short-range passage of RF waves between antenna elements by paths other than through the region of interest in the patient's body, including coupling that occurs within the array and near-field reflections.) In order to reduce this masking and enhance the dynamic range of the signals, in some embodiments a signal conditioning unit is used to adaptively cancel the background component out of the signals that are passed to the processing circuitry. To improve visibility of moving features, such as features in the heart, the signal conditioning unit or another element of the processing circuitry may even be configured to cancel all parts of the signals that do not vary over time.
System Description
[0041] FIG. 1 is a schematic, pictorial illustration of a system 20 for tracking and assessment of a feature in a body of a patient 26 , in accordance with an embodiment of the present invention. In this embodiment, an operator 22 , such as a physician, directs an ultrasonic beam from an ultrasound transducer 24 into the chest of patient 26 . The probe containing transducer 24 operates in Doppler mode, as is known in the art, in order to measure the velocity of blood flowing through a coronary artery of the patient, and specifically through a stent (not shown) that is implanted in one of the patient's coronary arteries. A console 28 drives transducer 24 and processes the signals that are output by the transducer in order to extract the Doppler information and displays the results on a monitor 30 . The operator steers the probe toward the location of the stent under guidance from system 20 , as explained in detail hereinbelow.
[0042] Aiming the ultrasound probe correctly under these circumstances is difficult: The stent is small and is typically embedded in clutter in the ultrasound image due to other anatomical features; and the stent and surrounding features of the heart are in continual motion. Therefore, system 20 uses radar imaging in order to find the location of the stent and guide operator 22 . For this purpose, an antenna 32 directs RF waves into the patient's chest. For good dielectric matching, in order to enhance the penetration of the RF waves into the body, a layer of a dielectric gel 33 is spread between the front surface of the antenna and the patient's skin. The gel may also have adhesive qualities, in order to aid in holding the antenna in place during the procedure.
[0043] Typically, gel 33 has a dielectric constant that is between 30 and 75. This value defines the effective dielectric constant of the antenna in its near-field. It is chosen to be close to the effective dielectric constant of the tissue layers in the path to the target region in the body. The desired dielectric constant may be achieved by increasing or decreasing the concentration of certain additives in the gel. For example, if a water-based gel is used, the additive may be an alcohol (such as ethanol), salt, sugar, or glycerin. Alternatively, a silicone gel may be used with an additive such as barium, having generally a dielectric constant greater than 70.
[0044] Antenna 32 is coupled by a cable or wireless link to a radar control unit 34 . The control unit comprises processing circuitry 36 , which drives the antenna to emit the RF waves into the body and processes the signals generated by the antenna due to reception of scattered waves from the body. Based on the received signals, circuitry 36 forms a 3D radar image of the interior of the body, and specifically, in the present embodiment, finds the location of the stent. These functions of circuitry 36 are described in detail hereinbelow.
[0045] In order to guide the direction of ultrasound transducer 24 , the position coordinates (location and orientation) of the transducer and of antenna 32 are registered in a common coordinate frame. For this purpose, system 20 includes a tracking subsystem, comprising a tracking transmitter 38 , which generates a field that is detected by sensors 40 and 42 on the antenna and on the ultrasound transducer, respectively. Transmitter 38 may, for example, generate a magnetic field, and sensors 40 and 42 may be magnetic sensors, as in the trakSTAR™ system distributed by Ascension Technology Corporation (Milton, Vt.). Alternatively, sensors 40 and 42 may be replaced by transmitting elements, which generate fields that are detected by a fixed sensor.
[0046] Further alternatively, other types of tracking devices may be used, such as optical, ultrasonic or mechanical position sensing devices, as are known in the art. For the sake of generality, the term “position transducer” is used herein to refer to the elements that are attached to ultrasound transducer 24 and antenna 32 , such as sensors 40 and 42 , for the purpose of finding their coordinates, regardless of the specific choice of position sensing technology. Additionally or alternatively, ultrasonic transducer 24 and antenna 32 may be mechanically fixed in a common frame of reference. A variety of alternative configurations are described in the above-mentioned U.S. patent application Ser. No. 12/127,544 and may similarly be used with the elements of system 20 .
[0047] In the system configuration shown in FIG. 1 , sensors 40 and 42 output signals to processing circuitry 36 . The processing circuitry processes the signals to find location and orientation coordinates of the sensors, and hence of antenna 32 and transducer 42 , in a common coordinate frame. Based on these coordinates, processing circuitry 36 registers the ultrasonic images formed by transducer 24 with the radar images formed by antenna 32 . The processing circuitry finds the location of the stent in the radar image, and may also estimate its orientation. On this basis, the circuitry guides operator 22 to aim transducer 24 toward the stent along the stent axis, i.e., along the direction of blood flow, in order to maximize the Doppler component in the ultrasound signals. For this purpose, the processing circuitry drives a guidance display 44 , which indicates to the operator how to aim the ultrasound transducer toward the target.
[0048] In an alternative embodiment (not shown in the figures), ultrasound transducer 24 may be held and manipulated by a robot arm, which is guided automatically by processing circuitry to aim the transducer in the desired direction.
[0049] Although FIG. 1 shows a particular type of antenna and mode of coupling the antenna to the patient's body, other antenna types and configurations may also be used for the purposes described herein. For example, the antenna may mounted in a cushion below the patient's back, in a wearable element that fits over the patient's body, or in any other suitable mount. Some alternative configurations of this sort are shown in the above-mentioned U.S. patent application Ser. No. 12/127,544.
[0050] FIG. 2 is a block diagram that schematically shows key elements of system 20 , and particularly of processing circuitry 36 , in accordance with an embodiment of the present invention. Some of these elements are described in greater detail hereinbelow. Antenna 32 is driven by and outputs signals to a feature detection subsystem 50 . The antenna typically comprises an array of antenna elements 48 , which are connected to a switching matrix 54 in a front end 52 of subsystem 50 . The switching matrix selects different sets of the antennas to transmit and receive signals at different, respective times and frequencies, in a predetermined temporal pattern. Typically, the sets comprise pairs of antennas—one transmitting and one receiving—although other groupings may also be used. The pattern of antenna control is described in detail hereinbelow.
[0051] A driver circuit 58 generates signals, at multiple different frequencies, for exciting the transmitting antennas and demodulates the signals received by the receiving antennas. Typically, the signals are in the range of about 400 MHz to about 4 GHz, although higher and lower frequencies outside this range may also be used. A signal conditioning unit 56 between the driver circuit and switching matrix 54 amplifies the outgoing and the incoming signals and also cancels background components in the received signals. This functionality is also described below.
[0052] Front end 52 outputs the demodulated received signals (as intermediate-frequency or baseband signals) to a digital data acquisition unit 60 , which samples and digitizes the signals. Unit 60 typically comprises a high-resolution analog/digital converter, such as a 14-bit converter, with suitable sampling circuits as are known in the art.
[0053] A target detection, measurement and tracking unit 62 receives and processes the digital samples. Unit 62 , as described in detail hereinbelow, processes the sampled signals in order to generate a 3D radar image of the interior of the chest of patient 26 . Within this image, elements having a dielectric constant that is different from that of the surrounding tissue, such as a metal stent in a coronary artery, stand out. On this basis, unit 62 identifies and measures the location coordinates of the stent relative to antenna 32 .
[0054] Since the heart is in constant motion, unit 62 may also track and model the motion of the stent in order to more precisely guide ultrasound transducer 24 . The direction of motion of the stent during the heart cycle also gives an indication of the direction of the stent axis (along which the ultrasound transducer should be aimed): Since the axis of the stent is oriented along the coronary artery in which the stent is implanted, and the coronary artery runs along the heart wall, the stent axis will typically be perpendicular to the direction of motion of the heart wall, and hence to the axis of motion of the stent in the radar image. As noted above, operator 22 is guided to aim ultrasound transducer 24 toward the stent in a direction along, or at least close to, the stent axis.
[0055] Although the present embodiment relates specifically to identification and tracking of a stent, the techniques and circuits that are described here may be used, by the same token, in locating and tracking other features in the coronary blood vessels, such as calcifications, as well as features elsewhere in the body.
[0056] A tracking unit 64 communicates with tracking transmitter 38 and receives position signals from position sensors 40 and 42 . The tracking unit processes these signals in order to compute the coordinates of ultrasound transducer 24 and antenna 32 in the frame of reference of transmitter 38 . The tracking unit may be a commercially-available device, such as in the above-mentioned FASTRAK system.
[0057] A guidance processor 66 receives the position (location and orientation) coordinates from tracking unit 64 and the position coordinates of the stent from feature detection subsystem 50 . Guidance processor 66 registers the coordinates of the stent in the coordinate frame of the tracking unit or, equivalently, registers the coordinates of ultrasound transducer 24 in the coordinate frame of antenna 32 , in which the stent coordinates have been found. The guidance processor is then able to compute the geometrical skew and offset between the present viewing axis of the ultrasound transducer and the desired viewing axis, which will intercept the stent along (or close to) the stent axis. Based on the computed skew and offset, the guidance processor may drive guidance display 44 to show operator 22 the required correction. For this purpose, the guidance display may show, for example, target crosshairs and directional arrows, or any other suitable sort of directional indication. Alternatively, console 28 may use the computed skew in adjusting the Doppler velocity readings to account for the angle of measurement relative to the flow.
[0058] Processing circuitry 36 typically comprises a combination of dedicated hardware circuits (such as in front end 52 and digital data acquisition unit 60 ) and programmable components. The front end circuits are described in detail hereinbelow. Target detection, measurement and tracking unit 62 and guidance processor 66 typically comprise programmable processors, such as a general-purpose microprocessor or a digital signal processor, which are programmed in software to carry out the functions that are described herein. Alternatively or additionally, these elements of circuitry 36 may comprise dedicated or programmable digital logic units such as an application-specific integrated circuit (ASIC) or a field-programmable gate array (FPGA). Although units 62 and 64 and processor 66 are shown, for the sake of conceptual clarity, as separate functional blocks, in practice at least some of the functions of these different blocks may be carried out by a single processor. Alternatively, the functions of a given block may be divided up among two or more separate processors.
Antenna Design and Operation
[0059] FIG. 3 is a schematic, pictorial illustration of antenna 32 , in accordance with an embodiment of the present invention. Antenna 32 is a planar ultra-wideband, unidirectional antenna, comprising an array of antenna elements 48 . The antenna is designed for high-permittivity surroundings, enabling transmission and reception of ultra-wideband signals to and from the human body with minimal loss. In the pictured embodiment, the antenna comprises twelve antenna elements 48 , which are spread in a rectangular plane to allow Cartesian acquisition of an image. Alternatively, the antenna may comprise a larger or smaller number of antenna elements, in a rectangular or non-rectangular array.
[0060] Each antenna element 48 comprises a planar element comprising a conductive radiator 70 , which is printed on a circuit board 72 . This circuit board serves as the front surface of antenna, which is brought into contact with the patient's body. Circuit board 72 comprises multiple conductive vias 74 surrounding each radiator 70 for isolating antenna elements 48 from one another. The antenna elements are enclosed from behind by a case 76 .
[0061] FIG. 4 is a schematic, exploded view of one of antenna elements 48 , in accordance with an embodiment of the present invention. Each antenna element is constructed as an ellipse-shaped slotted antenna, excited electrically at its center feed point. Circuit board 72 comprises a dielectric substrate, such as an FR4 laminate, with a component (front) side that includes radiator 70 and a ground plane 80 . The radiator shape is optimized with an elliptical template to maintain a low voltage standing wave ratio (VSWR), with high antenna gain and flatness at boresight. This flatness assures good coverage of the entire region of interest (ROI) in the patient's body with constant antenna gain.
[0062] The printed (rear) side of board 72 includes an excitation transmission line 82 feeding the center point of radiator 70 through a conductive via. Transmission line 82 comprises a fifty-ohm microstrip, with a micro-miniature coaxial (MMCX) connector (not shown) for connecting to front end 50 . Alternatively, other types of radiator shapes and feed lines may be used.
[0063] A conductive cavity 84 is attached to the component side of board 72 behind each radiator 70 in order to reduce antenna reverberations from back-lobe scattering and to increase the overall gain. (Antenna element 48 as shown in FIG. 4 has a nominal gain of 7 dBi at boresight.) Cavity 84 comprises a hollow waveguide 86 , with dimensions designed such that the cutoff frequency of the lowest propagating mode (TE10) in the waveguide is higher than the upper band frequency limit of antenna 32 ,
[0000]
i
.
e
.
,
f
cutoff
=
C
0
/
ɛ
r
2
a
,
[0000] wherein C 0 is the speed of light, ∈ r is the permittivity of the interior of the waveguide, and a is the largest transverse dimension of the waveguide. In the present example, with a frequency limit of 4 GHz, the depth of waveguide 86 is 15 mm. The waveguide creates an imaginary characteristic impedance, causing back-lobe radiation from radiator 70 to reflect from the cavity in phase with the back-lobe waves. This reflection enhances the external buffering of the antenna and attenuates non-TE and TM modes, and therefore reduces interference and noise.
[0064] Cross-coupling between antenna elements 48 can cause interference, which reduces the dynamic range and may saturate the receiver circuits. This cross-coupling is reduced in antenna 32 by appropriately setting the distance between the antenna elements in the array and by surrounding radiators 70 with conductive vias 74 , as noted above. The vias serve as an electric wall that prevents internal waves from traveling between elements. They also create a conductive continuity between ground plane 80 on the component side of board 72 and the top conductive transverse plane of waveguide 86 located on the print side.
[0065] Antenna 32 is sealed against liquids and gels, thus preventing unwanted materials from reaching the print side and cavities of the antenna elements. Case 76 , including cavities 84 , can be constructed from a molded plastic with a suitable conducting coating. Additionally or alternatively, the antenna elements may be printed on the molded plastic after coating. Although switching matrix 54 is shown and described herein as a part of processing circuitry 36 , it may alternatively be incorporated into antenna 32 or mounted adjacent to the antenna, thereby performing the switching alongside the patient and reducing the weight and rigidity of the cable from the antenna to control unit 34 .
[0066] Although antenna 32 is shown here as a unitary assembly containing antenna elements 48 , the antenna elements (of similar design to that shown in FIG. 4 ) may alternatively be used singly or as dual- or multi-element panels, which can be attached to different body locations. Multiple position sensors can be used to compute and register the respective positions of the antenna elements. In such embodiments, system 20 may be configured to measure and analyze both waves reflected from the region of interest of the body and waves transmitted through the region and scattered by the target.
Signal Switching and Processing
[0067] FIG. 5 is a block diagram that schematically shows details of feature detection subsystem 50 , in accordance with an embodiment of the present invention. As noted earlier, switching matrix 54 connects antenna elements 48 to the other circuits of front end 52 . Each antenna element connects to a respective single-pole double-throw (SPDT) switch 90 , which determines whether the switch is to transmit or to receive waves at any given time. The transmit antenna element is selected, from among the multiple antenna elements, by a transmit switch 92 , while the receive antenna element is selected by a receive switch 94 . The switching matrix thus permits any pair of the antenna elements to be selected as the transmitter and receiver at any given time.
[0068] Switching matrix 54 is designed for high isolation between channels, typically better than 40 dB over the entire frequency range of antenna 32 . Switches 90 , 92 and 94 are digitally controlled by a digital output control module 104 and allow fast (non-mechanical) switching. This fast switching is required in order to allow the entire waveform sequence of different antenna pairs and frequencies to be completed in a short frame time, as described hereinbelow. For this purpose, matrix 54 is typically configured to achieve a switching time of less than 1 μs.
[0069] Driver circuit 58 comprises a broadband signal generator 98 , which generates the RF excitation waveform to drive the transmitting antenna elements, and a receiver 114 , which receives and demodulates the signals generated by the receiving antenna elements. Signal generator 98 and receiver 114 are both synchronized and sweep their frequencies according to a predefined frequency plan, which is shown in FIG. 6 , based on a shared local oscillator 96 . The frequency plan specifies the frequencies and power levels to be generated by the signal generator, in synchronization with an external trigger. The driving waveform entering signal conditioning unit 56 from signal generator 98 is sampled by a broadband coupler 100 , amplified by a power amplifier 102 according to the required transmit power level, and transferred to switching matrix 54 .
[0070] Receiver 114 is a tuned super-heterodyne receiver, which is able to adjust its bandwidth and gain according to the received signal. The receiver demodulates the received signals coherently, in synchronization with local oscillator 96 , in order to extract both the amplitude and the phase of the signals. The complex ratio between the transmitted and received signals, as measured by detection, measurement and tracking unit 62 for each antenna pair at each selected frequency, indicates the frequency response along corresponding paths through the region of interest. This region includes the chest, thoracic cavity, beating heart and the stent itself.
[0071] Despite the measures described above for reducing coupling between different antenna elements 48 in antenna 32 , the signals received from antenna 32 by signal conditioning unit 56 may still include a strong background component due to the direct coupling between the transmitting and receiving antenna elements. This background component raises the noise level due to transmitter nonlinearity and impurities in the transmitted signal and can even cause receiver 114 to saturate. It is therefore desirable to reduce the level of the background component that reaches the receiver in order to enhance the dynamic range of the radar image.
[0072] For this purpose, signal conditioning unit 56 comprises an amplitude and phase modulator, referred to here as an IQ modulator 108 , which receives the sampled RF excitation waveform from coupler 100 . The IQ modulator modifies the phase and amplitude of the sampled signal, under the control of an analog output control module 110 , so as to generate an anti-phased signal matching the background component that is to be canceled. The amplitude and phase values of IQ modulator 108 are periodically updated and are then kept constant per frequency and per channel until coupling values change significantly and need updating. In other words, IQ modulator 108 outputs a signal that is equal in amplitude to the background component but 180° out of phase. A coupler 106 adds this anti-phased signal to the received signal from switching matrix 54 and thus cancels the background component without degrading the actual radar signal from the body. An amplifier 112 amplifies the signal following background cancellation for input to receiver 114 .
[0073] FIG. 6 is a timing diagram that schematically illustrates a temporal excitation pattern that front end 52 applies to antenna 32 , in accordance with an embodiment of the present invention. The front end generates a sequence of frames 120 . Each time a radar measurement is triggered (ten times per second, for example), the frame defines a sweep of the excitation signal both in frequency and over spatial channels (antenna pairs). Each frame 120 comprises multiple frequency sub-frames 122 according to the number of frequencies to be used in image reconstruction. In the example shown in FIG. 6 , there are 128 such sub-frames, each lasting 750 μs. The frequencies in this example, as noted above, span the range between 400 MHz and 4 GHz.
[0074] Each sub-frame 122 begins with a settling time 126 (typically a few hundred microseconds) for locking the amplitude and phase of signal generator 98 . Following this initial delay, switching matrix 54 selects different channels 124 in sequence. Each channel uses one transmitting antenna element and one receiving antenna element, up to a total of n channels (for example, one hundred such channels in the example shown in FIG. 6 , each open for 5 μs). During each channel period, detection, measurement and tracking unit 62 collects samples of the received signal from receiver 114 for subsequent use in multi-frequency/multi-channel radar image reconstruction.
[0075] In alternative embodiments (not shown in the figures), other sorts of channel configurations may be used. For example, in monostatic configurations, a selected antenna element may serve as both transmitter and receiver, as opposed to bistatic or multistatic configurations, in which each antenna either transmits or receives. As another option, antenna elements may simply transmit and receive broadband RF pulses, rather than multiple narrowband pulses as in the embodiment described above.
Method of Operation
[0076] Based on the collected samples of the received signals, detection, measurement and tracking unit 62 detects small reflecting volumes within the region of interest (ROI) in the patient's body. As noted above, the corresponding reflections arise at the boundaries of media having different dielectric properties. The information provided by coherent detection of the signals over the broad range of frequencies covered in each frame is equivalent mathematically to the temporal information that would be provided by reflection of a single short pulse. The locations of the reflectors may be found by integrating over the propagation paths of the reflected waves, using an inverse spherical Radon transformation, for example.
[0077] In an embodiment of the present invention, detection, measurement and tracking unit 62 implements a first-order approximation of the inverse spherical Radon transform: For each voxel (x, y, z) in the ROI and for each frequency f and pair of antenna elements, a complex weight W(x,y,z,f,pair) is pre-calculated, either using an empirical calibration procedure or mathematical modeling. The weight is, in effect, the normalized complex amplitude (with conjugated phase) of the reflection that would be received at the receiving antenna in the pair from a point object at location (x,y,z) when irradiated by the transmitting antenna with a wave of frequency f. Because the body tissue through which the waves propagate is inhomogeneous, the weights may be adjusted, either empirically or by model calculation, to account for the specific tissue layers (skin, fat, muscle, lungs, etc.) through which the waves pass.
[0078] The set of weights thus derived defines a sort of matched filter. Detection, measurement and tracking unit 62 applies this filter to the matrix of complex signals Sig(f,pair) that it receives in any given frame in order to compute the reflection intensity V for each voxel, as a weighted sum over the received signals:
[0000]
V
(
x
,
y
,
z
)
=
∑
pair
∑
f
W
(
x
,
y
,
z
,
pair
,
f
)
·
Sig
(
pair
,
f
)
(
1
)
[0000] The inventors have found that this simplified approximation of the inverse spherical Radon transform is both robust and computationally efficient.
[0079] FIG. 7 is a flow chart that schematically illustrates a method for measuring blood flow through a stent, in accordance with an embodiment of the present invention. The method is described hereinbelow, for the sake of clarity, with reference to the elements of system 20 that have been described above, but the same techniques may similarly be implemented in other system configurations. Furthermore, the elements of this method that relate to locating the stent in the body of patient 26 may likewise be applied, mutatis mutandis, for locating other features, both natural and artificial, in the coronary blood vessels, as well as elsewhere in the body.
[0080] Front end 52 drives antenna 32 to emit and receive RF waves over multiple frequencies and spatial channels (antenna pairs), at a scanning step 130 , as described above. Detection, measurement and tracking unit 62 collects samples of the received signals and applies the weights defined in equation (1) to transform the signal values to voxel intensities, at an image reconstruction step 132 . To improve the clarity of the image, the processing circuitry may apply additional image processing operations, such as subtracting the mean voxel value from all voxels in the image. The mean value may be smoothed over multiple successive images using a recursive filter. Unit 62 then identifies the coordinates of the target feature, i.e., the stent or another strong reflector, in the 3D image, at a target identification step 134 .
[0081] Features in the coronary arteries (or elsewhere in the heart), such as the stent, move regularly with the heart rhythm, as well as with chest movement due to respiration. In order to guide the ultrasound transducer, detection, measurement and tracking unit 62 tracks the motion of the target in the successive images, at a target tracking step 136 . For example, unit 62 may apply a Kalman filter, as is known in the art, to estimate the motion trajectory of the target.
[0082] Guidance processor 66 registers the coordinates of ultrasound transducer 24 with antenna 32 , at a coordinate registration step 138 . The processor uses the position coordinates provided by position sensors 40 and 42 at this step, as explained above. Based on these coordinates, the processor registers the ultrasound beam in the coordinate frame of the 3D image that was reconstructed at step 132 .
[0083] Guidance processor 66 drives guidance display 44 to guide operator 22 in aiming the ultrasound beam toward the target, at an aiming step 140 . It could be possible but would probably be impractical for a human operator, to move ultrasound transducer 24 continually back and forth in synchronism with the motion of the heart. (Such tracking could be feasible for a robot driven by the processing circuitry.) To alleviate this difficulty, the guidance processor selects a single location within the trajectory of motion found at step 136 and guides the operator to aim at the selected location. Console 28 measures the flow through the stent at this location, at a flow measurement step 142 , and thus provides an indication of the extent of any restenosis.
[0084] To select the target location at step 140 , guidance processor 66 may, for example, find the center of mass of the trajectory found at step 136 , and then choose a point that is displaced from the center toward the end of the trajectory that has the greater dwell time, which is the diastolic end. Blood flow through the coronary arteries occurs mainly during diastole, so that the diastolic end of the trajectory will give the strongest Doppler signal. Furthermore, aiming the ultrasound transducer toward the end of the trajectory with the greater dwell permits the ultrasonic beam to capture the stent for a longer part of each heart cycle and thus improves the signal/noise ratio.
[0085] It will be appreciated that the embodiments described above are cited by way of example, and that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described hereinabove, as well as variations and modifications thereof which would occur to persons skilled in the art upon reading the foregoing description and which are not disclosed in the prior art. | Diagnostic apparatus ( 20 ) includes an antenna 32 , which is configured to direct radio frequency (RF) electromagnetic waves into a living body and to generate signals responsively to the waves that are scattered from within the body. Processing circuitry ( 36 ) is configured to process the signals so as to locate a feature in a blood vessel in the body. | 0 |
The invention herein described relates generally to food service cabinets particularly useful in commercial kitchens or by caterers to facilitate processing and handling of prepared food products.
BACKGROUND
In the food service industry a variety of cabinets have been provided for various purposes. These cabinets include storage, transport and/or busing cabinets, cold cabinets, hot cabinets, refrigerated cabinets, proof cabinets, heat and hold cabinets, warming cabinets, banquet cabinets, etc. Typically, the cabinets stand about 5-7 feet tall, have a depth of about 2-3 feet and come in widths ranging from about 2-6 feet. Both insulated and uninsulated cabinets have been provided, and typically the cabinets have one or more doors opening on the front or back sides.
In these cabinets the food products are usually supported on horizontal shelves arranged vertically from bottom to top within the cabinet. Various types of shelves have been used, these including wire racks, baskets, trays, plate carriers, etc. The shelves are usually supported at opposite side edges thereof on ledges either formed integrally in the sidewalls of the cabinets or attached to the sidewalls of the cabinets. For example, cabinets have been provided with corrugated interior sidewalls wherein the corrugations define a vertical array of equally spaced apart ledges. The ledges also have been formed by angles or pan slides attached to the sidewalls of the cabinet. Although these various types of shelf supports have proven to be effective and successful over the years, there still remains a need for improved alternative means for supporting the shelves in a cabinet. An improved shelf support desirably would be easily removable by a simple manipulation to facilitate removal of the shelf support for cleaning or for shelf height adjustment. Also, an improved shelf support would be relatively economical and easy to fabricate.
In some food service cabinets heated or cooled air is circulated within the cabinet to contact the food to heat or cool the food or to maintain the temperature of the food. In one known type of cabinet an open top of the cabinet is closed by a removable heat transfer unit which is interchangeable with other heat transfer units depending on the particular function to be performed by the cabinet. The heat transfer units which fit on top of the cabinet may be refrigeration or freezer units, warming units or baking units, among others. The heat transfer units typically include an air intake, a fan or fans for circulating air, a heating or cooling device to transfer heat to or from the circulating air, and an outlet for the heated or cooled air. The units are intended to be positioned over and sealed against an opening in the top of the cabinet. The air inlet then communicates directly with the cabinet area while the treated air outlet communicates with a vertically extending duct on the rear wall of the cabinet. The fan or fans draw air from the intake, force it past the heating or cooling device, through the outlet, into the tunnel, and then through many louvers, slots or holes in the duct walls into the interior of the cabinet. In order to hold the heat transfer unit stationary atop the cabinet, latches are provided. It would be desirable to provide interchangeable heat transfer units which are easy to remove from atop the cabinets and which do not require the need for latches to hold the units in place.
Many food service cabinets are provided with a shelf stop on the cabinet doors to prevent forward and rearward shifting of the shelves. These shelf stops may be removable to facilitate cleaning of the cabinet interior. Typically the shelf stops are sheet metal channel members which are punched to form keyholes for mating with pins attached to the inside wall surface of the door. The orientation of the keyhole dictates a top and bottom end of the shelf stop thereby requiring the user to take the time to determine which is the top or bottom end when attaching the shelf stop to the door. It would be desirable to provide an improved means for removably attaching a shelf stop to the inside surface of the cabinet door, as well as other elongate channel members such as posts to inside wall surfaces of the cabinet and which improved means is easy to form in the sheet metal channel members.
SUMMARY OF THE INVENTION
The present invention provides an improved food service cabinet that satisfies one or more of the aforesaid needs or objectives. The food service cabinet in a preferred form embodies a unique shelf support rail construction and mounting arrangement which provides for easy and quick removal of the shelf support rails for cleaning and/or adjustment. The preferred form of food service cabinet further includes a unique construction of channel members employed in the cabinet as support posts and tray stops, for example, which construction coacts with catches on walls of the cabinet for providing quick and easy removable attachment of the channel member to the wall. A further feature of a preferred form of food service cabinet according to the invention is the provision of a removable top unit for closing an open top of a cabinet enclosure, the top unit forming a continuation of the cabinet enclosure and having essentially full width hand grips integrally embodied in sheet metal side walls of the top unit.
More paticularly, a food service cabinet according to one aspect of the invention is characterized by an enclosure, a pair of upright posts in the enclosure, and a shelf support rail for supporting a shelf along an edge of the shelf. The shelf support rail extends horizontally between the upright posts and is removably supported at end portions thereof by the upright posts. Each post has an outer surface coplanar with the outer surface of the other and a horizontal slot extending inwardly from the outer surface of the post to an inner surface of the post which extends upwardly from the horizontal slot. The shelf support rail at least at the end portions thereof are generally L-shape in cross section and have a normally upright leg for interlocking engagement in the horizontal slots in the upright posts and a normally horizontal leg atop which an edge of a shelf may rest and thereby be supported. The normally upright leg is transversely stepped to form an upper upright portion for engaging the inner surface of the post above the horizontal slot, a lower upright portion for engaging the outer surface of the post below the horizontal slot, and an intermediate transversely extending portion joining together the upper and lower upright portions. The intermediate portion extends through the horizontal slot and is supported atop a bottom edge surface of the horizontal slot. The horizontal slot is of sufficient height and sufficient clearance is provided inwardly of the inner surface of the post to allow rotation of the upper upright portion in a direction away from the inner surface of the post about a horizontal axis to an angularly rotated position permitting withdrawal of the normally upright leg from the horizontal slot.
According to another aspect of the invention there is provided in a food service cabinet a wall having an interior surface, at least one catch on the wall, and an upright member attached by the catch or catches to the wall. Each catch has a stem portion extending from the interior surface of the wall and a wider head portion spaced from the interior surface of the wall and forming a slot therebetween. The upright channel member is of generally C-shape cross section and has a pair of legs extending from a base to respective inturned flanges. The inturned flanges include a keyhole for each catch, the keyhole having a lower portion for passage therethrough of the head portion of the catch and a reduced width upper portion for receiving the base. The keyhole is uniquely formed by opposed notches in the inner edges of the inturned flanges. The reduced width upper portion of the keyhole preferably is formed by oppositely sloping shoulder surfaces at the top of the notch in the inturned flanges which oppositely sloping shoulder surfaces engage the stem portion of the catch in a wedge-like manner. Preferably, the notches in the inturned flanges are vertically as well as horizontally symmetrical.
A food service cabinet according to a further aspect of the invention is characterized by an enclosure having an open top, and a removable top unit for closing the open top. The top unit includes hand grips at opposite sheet metal side walls thereof and the hand grips extend substantially the full width of the side walls. Each sheet metal side wall has a lower recessed wall portion from which a laterally extending rim projects to form the hand grip.
The foregoing and other features of the invention are hereinafter fully described and particularly pointed out in the claims, the following description and the annexed drawings setting forth in detail a certain illustrative embodiment of the invention, this being indicative, however, of but one of the various ways in which the principles of the invention may be employed.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a preferred embodiment of food service cabinet according to the invention.
FIG. 2 is a perspective view of the food service cabinet of FIG. 1, with portions broken away and shown in section.
FIG. 3 is a vertical cross-sectional view of the food service cabinet.
FIG. 4 is a fragmentary broken cross-sectional view of the food service cabinet taken along the line 4--4 of FIG. 3.
FIG. 5 is a fragmentary cross-sectional view of the food service cabinet taken along the line 5--5 of FIG. 3.
FIG. 6 is a fragmentary cross-sectional view of the food service cabinet taken along the line 6--6 of FIG. 5.
FIG. 7 is a fragmentary cross-sectional view of the food service cabinet taken along the line 7--7 of FIG. 3.
DETAILED DESCRIPTION
Referring now in detail to the drawings and initially FIGS. 1 and 2, a preferred form and type of food service cabinet according to the invention is designated generally by reference numeral 20. The illustrated cabinet is intended primarily for use as a mobile banquet cabinet designed to move food from a central kitchen to a distant area or areas for serving. Although the illustrated cabinet represents a preferred form of food service cabinet according to the invention, it will be appreciated and should be understood that the hereinafter described features of the invention will have application to other types of cabinets both separately as well as collectively.
The cabinet 20 generally comprises a box-like enclosure 21 mounted atop a base 22 which is provided with casters 23. Two or more of the casters 23 may be of the swivel-type and the remaining casters of the fixed-type, as is conventional. One or more of the casters may also be provided with a foot brake (not shown) as is conventional.
The box-like enclosure 21 includes a bottom wall 25, a front wall 26, a back wall 27 and opposite side walls 28 and 29. The walls 25-29 form therebetween a large interior compartment which is subdivided into left and right shelf compartments 30a and 30b for housing respective vertical rows of shelves, one shelf being seen at 32 in FIG. 3. The front wall 26 of the enclosure 21 is provided with left and right openings for providing access to the shelf compartments 30a and 30b, respectively. The openings are closed by respective left-hand and right-hand doors 36a and 36b. The doors 36a and 36b are provided with conventional latches 38a and 38b for holding the doors closed and hinge mounts 39a and 39b. As illustrated at the left in FIG. 2, each door can be swung open a full 270° and flush against the adjacent side wall to make loading and unloading of the cabinet quick and easy.
The doors 36a and 36b are of a double walled, insulated construction as are the walls 25-29 of the enclosure 21. The interior and exterior walls of each door or enclosure wall may be formed from stainless steel sheet metal and may contain 2 inch thick insulation, for example. The stainless steel walls may be conventionally joined together using, in particular, rivet-locked hem joints which provide a tight seam and impart rigidity to the wall panel. Although not shown, smooth cove corners may be provided around the interior base and enclosure side walls to eliminate places for food particles or grease to accumulate.
As illustrated in FIGS. 1 and 2, each side wall 28, 29 may be provided with a handle 40. The handle 40 preferably is recessed into the side wall to make it easier for the cabinet to be moved through a congested hallway, aisle or the like.
Although the illustrated enclosure 21 is provided with two shelf compartments 30a and 30b, the enclosure may have only a single shelf compartment or more than two shelf compartments, as may be desired. If plural shelf compartments are provided, they may be open to one another as shown or separated by an interior wall or walls. Each shelf compartment may have associated therewith a respective opening closed by a respective door, or a single opening and door may be shared by more than one shelf compartment. A variety of these different cabinet configurations are well known in the art.
The top edges of the enclosure walls 25-29 define an opening in the top of the enclosure 21 which is closed by a top unit 44. The top unit is intended to be easily removable for cleaning and/or exchange with one or more other top units that may perform a variety of functions in addition to closing the top of the cabinet enclosure. The top unit for example may be any one of a number of heat transfer units including refrigeration or freezer units, warming units, proofing units or baking units, among others. In the illustrated cabinet, the top unit is a heating unit. The general characteristics of the top unit will first be described and then followed by specific features of the illustrated top unit relating to its function as a heating unit.
As best seen in FIGS. 3 and 4, the top unit 44 is characterized by an upper or head portion 46 forming a continuation of the cabinet enclosure 21 and a lower or neck portion 47. The head portion 46 projects laterally beyond the neck portion about the perimeter of the top unit to form on its underside a shoulder 48 that rests atop the top perimeter surface of the enclosure walls 26-29. As is preferred, the shoulder 48 is provided with a perimeter gasket 49 for sealing the joint between the shoulder surface and top surface of the enclosure walls 26-29. As shown, the head portion has a perimeter corresponding in size and shape to the perimeter of the enclosure 21.
When the top unit 44 is set atop the enclosure 21, the neck portion 47 extends into the interior of the enclosure. The sides of the neck portion engage the interior wall surfaces of the enclosure walls 26-29 to prevent horizontal rotation or shifting of the top unit relative to the cabinet enclosure. As shown and preferred, the neck portion of the top unit closely corresponds in cross-sectional size and shape to the opening in the top of the cabinet enclosure.
As above indicated, the top unit 44 is intended to be easily removable for cleaning and/or exchange with one or more other top units. This is greatly facilitated by the provision of front and rear hand grips extending laterally and preferably substantially the full width of the top unit. As seen in FIG. 3, the front and back sheet metal walls 50 of the head portion of the top unit are recessed to form projecting rims 51 extending along the upper edges of the front and back walls and forming the hand grips. At its outer end, each projecting rim or overhang 51 is provided with a downwardly extending lip 52 which functions as a finger catch for more secure gripping of the top unit. Also, the recessed lower portion of the wall 50 has formed therein along an upper edge thereof an outwardly opening groove 56 extending the full width of the rim to provide ample finger room for engaging the underside of the rim when lifting the top unit. As will be appreciated, two servicemen may position themselves in front of and behind the cabinet and position their fingers beneath the projecting rims 51 for lifting the top unit off of the cabinet enclosure.
Referring now to the illustrated top unit 44 in relation to its function as a heating unit, the top unit has associated with each shelf compartment 30a and 30b a fan 60 which draws air in through an inlet 61 and past an electric resistance heating element 62. After passing over the heating element, the air is forced out through an outlet opening 63 in the bottom wall 64 of the unit which coincides with the open top of a vertically extending flow distribution duct 65 attached to the back wall 27 of the cabinet. The duct 65 is formed by a sheet metal channel member of generally C-shape cross section having at the end of each leg an inturned flange for attachment to the inner wall of the back panel at a central location in relation to the respective shelf compartment. When the top unit is set atop the enclosure, preferably the bottom wall 64 of the top unit will be positioned close to if not in contact with the top edge of the duct to prevent flow losses at the junction between the outlet opening in the bottom wall of the top unit and the open top of the duct. Accordingly, the heated air will flow downwardly through the duct and into the interior of the shelf compartment via an array of openings 67 provided in the base of the U-shaped duct. Air exiting the holes at the base of the duct will be directed laterally inwardly for heating the interior of the shelf compartment from top to bottom.
In addition to providing for uniform distribution of heated air through the shelf compartment (or cooled air in the case of a refrigeration or freezer unit), each duct 65 also functions as a shelf stop for shelves in the shelf compartment. Although only one shelf is illustrated in FIG. 3, a number of shelves may be located within each shelf compartment. Various types of shelves may be used, these including wire racks, baskets, trays, plate carriers, etc.
As illustrated in FIGS. 2, 3 and 7, each shelf 32 is supported by and between a pair of shelf support rails 70. Each shelf support rail in turn is supported at the ends thereof by a pair of upright posts 72. Accordingly, an upright support post is provided at the four corners of each shelf compartment. In the manner described below in greater detail, the shelf support rails are removably engaged in horizontal slots 73 in the support posts. As shown, each support post includes a number of such horizontal slots vertically spaced apart along the post to permit height adjustment of the shelf supported by the shelf support rail. The horizontal slots, for example, may be uniformly vertically spaced apart on one and one-half inch centers or any other desired spacing.
In FIGS. 2, 3 and 7, details of the shelf support rails and posts, and their manner of interengagement, are shown. In the illustrated cabinet each post 72 is formed by two angularly positioned walls with a front wall 76 extending generally parallel to the shelf support rail 70 supported thereon and a side wall 77 extending generally perpendicular to the shelf support rail. Preferably the two walls intersect at right angles to one another as shown and the front wall has an outer surface 78 coplanar with the outer surface of the other post supporting the opposite end of the same shelf support rail. Each horizontal slot 73 extends through the front wall and into the side wall to a vertically extending slot 79 forming a T with the horizontal slot 73. The vertical slot 79 at least extends vertically upwardly from the horizontal slot to define an inner surface 80 of the post, although preferably the vertical slot extends both upwardly and downwardly to provide a universal post that may be inverted for installation at either the front or back of the shelf compartment.
The shelf support rail 70 is generally L-shaped having a normally upright leg 82 for interlocking engagement in the horizontal slots and a normally horizontal leg 83 for supporting the edge of the shelf as best seen in FIG. 7. The normally upright leg 82 is transversely stepped to form an upper upright portion 85 for engaging the inner surface 80 of the post 72 above the horizontal slot 73, a lower upright portion 86 for engaging the outer surface 78 of the post below the horizontal slot, and an intermediate portion 87 joining together the upper and lower upright portions. The intermediate portion extends through the horizontal slot and is supported atop a bottom edge surface 88 of the horizontal slot. The horizontal slot is of sufficient height and sufficient clearance is provided inwardly of the inner surface 80 of the post to allow rotation of the upper portion of the normally upright leg 82 away from the inner surface of the post about a horizontal axis to an angularly rotated position permitting withdrawal of the normally upright leg from the horizontal slot.
As will be appreciated, the shelf support rail 70 has a cross-sectional shape that is similar to the profile of a common peg board hook. Moreover, the shelf support rail is attached at opposite ends thereof to respective posts in a manner similar to the manner in which a peg board hook is interlocked in a hole in a peg board. That is, the shelf support rail initially is rotated such that its normally upright leg 82 can be inserted at end portions of the rail into the horizontal slots 73 in a cooperating pair of posts. The normally upright leg is inserted into the slot sufficiently until the leading end thereof enters the vertical slot 79 at which point the shelf support rail may be further inserted into the slot and also rotated with its normally horizontal leg 83 moving downwardly and its normally upright leg moving upwardly to the position shown in FIG. 7. In this position, the upper portion 85 of the normally upright leg engages the inside surface 89 of the post whereas the lower portion 86 of the normally upright leg engages the outer surface 78 of the post to hold the shelf support rail against any appreciable horizontal movement in a direction perpendicular to its length dimension. To prevent horizontal movement of the shelf support rail in its length direction, the ends of the shelf support rail engage the ends of the horizontal slots 73 in the posts, the spacing between the ends of corresponding slots in the posts being only slightly greater than the length of the shelf support rail or at least that portion thereof engaged in the horizontal slots. As will be appreciated, the normally horizontal leg 83 of the shelf support rail may be extended beyond the posts to provide a longer shelf support surface if desired. Also, only the end portions of the shelf support rail engaged in the slots in the posts need have the above described configuration, although preferably the shelf support rail is of uniform cross section over its full length, this providing obvious manufacturing benefits.
The shelf support rail 70 will normally be held against any appreciable vertical movement by the weight of the shelf supported thereon, as well as the weight of any items supported on the shelf. The shelf weight applies a force acting downwardly on the normally horizontal leg 83 of the shelf support rail, this serving to hold the shelf support rail locked in position against any rotation that might result in the shelf support rail from disengaging from the support posts.
Although the support posts 72 employed in the illustrated cabinet are similar in the foregoing respects, the posts may be integrally embodied in different structural elements. At the corners of the cabinet enclosure 21, the support posts are integrally embodied in upright channels 90 of C-shape cross section. The base and one leg of the channel form the support post, whereas the remaining structure aids in mounting the support post to the enclosure side walls and also strengthening of the post (Such mounting is effected in the same manner as the hereinafter described shelf stop). Because of the T-shaped slot provided in the side wall of each support post and symmetry about vertical and horizontal center lines, the channels 90 may be identical thereby minimizing the total number of parts that need to be fabricated. The support posts are mounted in one orientation at the front of the enclosure and at an inverted orientation at the rear of the enclosure, such that the support posts are symmetrical with respect to a vertical plane extending parallel to the width dimension of the cabinet enclosure.
The posts 72 located between the two shelf compartments are formed integrally in front and rear channels 92 and 93 of C-shape cross section. In each of these channels, the front and side walls of each support post are formed by the legs and inturned flanges of the channel, with the inturned flanges forming the side walls and the legs forming the front walls of the support posts. The bases of the channels are attached to the inner wall surfaces of the front and rear walls 26 and 27. As best seen in FIG. 2, the legs of the rear channel 93 are sufficiently deep to accommodate the presence of the ducts 65 against which the rear edges of the shelves 32 will abut when fully inserted into the shelf compartments.
When the shelf is fully inserted into the shelf compartment, forward and rearward shifting of the shelf is prevented by the duct at the back of the compartment and a shelf stop 93 attached to the inner wall surface of the door as shown in FIG. 3. As further shown in FIGS. 5 and 6, the shelf stop 93 is a unitary channel member of C-shape cross section having a pair of legs 94 extending from a base 95 and terminating at inturned flanges. The shelf stop is attached to the inner wall surface 97 of the respective door 36 by catches or buttons 100 on the door. As shown, three vertically aligned catches are provided and the shelf stop is provided with corresponding keyholes for the catches. Preferably the catches are equally spaced apart.
According to the present invention, the keyhole 102 for each catch is formed by opposed notches 103 in the inturned flanges. The notches have recessed sides 104 forming therebetween the wide opening of the keyhole and upper oppositely sloped shoulder surfaces 105 forming therebetween the reduced width upper portion of the keyhole.
Each catch includes a base or stem 108 engagable by the shoulder surfaces 105 of the inturned flanges of the channel member in a wedge-like manner vertically to support the channel member. The catch further includes a flange or head portion 109 spaced from the interior surface 97 of the wall for capturing therebetween a portion of the inturned flanges to hold the inturned flanges 96 against the interior surface of the wall in an engaged position of the channel member. The channel member is vertically upwardly moveable from such engaged position to a release position vertically withdrawing the inturned flanges from between the catch flange and aligning the wide opening 110 with the catch flange for permitting passage of the catch flange through the opening when the channel member is moved horizontally away from the interior surface of the wall.
In the illustrated embodiment, the catch is in the form of a button with the base or stem 108 being formed by an upset central portion of the button and the flange or head portion 109 being formed by a annular flange extending circumferentially around the base. This construction allows the catch to be mounted to the door panel as by means of a central rivet 113 or other fastener without having to be concerned with a specific angular orientation of the catch inasmuch as the catch may be rotated about its center axis and still function as aforedescribed.
In the same manner, the upright channels 90 may be attached to respective walls of the cabinet enclosure which walls are provided with catches. That is, the inturned flanges of the C-shape channels may be notched as shown in FIG. 5 to receive and interengage with a corresponding catch on the wall to which the channel is to be mounted. Preferably at least two catches and corresponding recesses are provided normally near the top and bottom of the channel.
Although the invention has been shown and described with respect to a preferred embodiment, it is obvious that equivalent alterations and modifications will occur to others skilled in the art upon the reading and understanding of this specification. The present invention includes all such equivalent alterations and modifications, and is limited only by the scope of the following claims. | A food service cabinet embodies a unique shelf support rail construction and mounting arrangement which provides for easy and quick removal of the shelf support rails for cleaning and/or adjustment, a unique construction of channel members employed in the cabinet as support posts and tray stops, for example, which construction coacts with catches on walls of the cabinet for providing quick and east removable attachment of the channel member to the wall, and a removable top unit for closing an open top of a cabinet enclosure, the top unit forming a continuation of the cabinet enclosure and having essentially full width hand grips integrally embodied in sheet metal side walls of the top unit. | 0 |
TECHNICAL FIELD
[0001] The present invention relates to a gravure preparation processing system, and more particularly, to a fully automatic gravure preparation processing system capable of performing an unattended operation even in the nighttime.
BACKGROUND ART
[0002] Conventionally, gravure preparation plants described in Patent Documents 1 to 6 have been known.
[0003] As can be seen from the drawings of Patent Documents 1 to 3, a manufacturing line for a gravure printing roll has conventionally been constructed of an industrial robot and a stacker crane used in combination.
[0004] In the manufacturing line using the stacker crane, processing is performed in each of various processing units under a state in which a roll to be prepared is chucked at the stacker crane with use of a cassette-type roll chuck rotary transportation unit.
[0005] However, in the case of such a manufacturing line using the stacker crane, the roll to be prepared is sequentially transferred to the various processing units under the state in which the roll to be prepared is chucked with use of the cassette-type roll chuck rotary transportation unit, and hence there arises a problem in that a longer time period is required accordingly.
[0006] Further, in recent years, there have been customer needs for more flexible customization of the manufacturing line.
PRIOR ART DOCUMENTS
Patent Documents
[0007] Patent Document 1: JP 10-193551 A
[0008] Patent Document 2: WO 2007/135898
[0009] Patent Document 3: WO 2007/135899
[0010] Patent Document 4: JP 2004-223751 A
[0011] Patent Document 5: JP 2004-225111 A
[0012] Patent Document 6: JP 2004-232028 A
[0013] Patent Document 7: JP 2008-221589 A
SUMMARY OF INVENTION
Technical Problem
[0014] The present invention has been made in view of the above-mentioned circumstances of the conventional technologies, and it is therefore an object thereof to provide a fully automatic gravure preparation processing system having high degrees of freedom, which is capable of manufacturing a gravure printing roll more quickly as compared to a conventional case, achieving space saving, performing an unattended operation even in the nighttime, flexibly customizing a manufacturing line, and satisfying various customer needs.
[0015] In order to achieve the above-mentioned object, a fully automatic gravure preparation processing system according to the present invention includes: a processing room-A having a handling area of a first industrial robot for chucking and handling a roll to be prepared; a processing room-B having a handling area of a second industrial robot for chucking and handling the roll to be prepared, the processing room-A and the processing room-B being communicable to each other; at least one processing apparatus arranged within the handling area of the first industrial robot of the processing room-A, the at least one processing apparatus being selected from among a roll stock apparatus, a photosensitive film coating apparatus, an electronic engraving apparatus, a laser exposure latent image forming apparatus, a degreasing apparatus, a grinding wheel polishing apparatus, an ultrasonic cleaning apparatus, a copper plating apparatus, a surface hardening film forming apparatus, a developing apparatus, an etching apparatus, a resist image removal apparatus, and a paper polishing apparatus; and at least one processing apparatus arranged within the handling area of the second industrial robot of the processing room-B, the at least one processing apparatus being excluded in the arrangement of the processing room-A, the at least one processing apparatus of the processing room-A and the at least one processing apparatus of the processing room-B being installable and dismantlable. The first industrial robot and the second industrial robot are configured to transfer the roll to be prepared therebetween when preparation processing is performed.
[0016] In this manner, the roll to be prepared is transferred between the first industrial robot and the second industrial robot, and thus the gravure printing roll can be manufactured more quickly as compared to the conventional manufacturing line for a gravure printing roll using a stacker crane. Further, the roll to be prepared is transferred between the first industrial robot and the second industrial robot, and hence the stacker crane becomes unnecessary, which leads to such an advantage that space saving can be achieved. Further, the series of processing can be performed fully automatically based on predetermined programs, and hence there is also such an advantage that an unattended operation can be performed even in the nighttime.
[0017] Further, the processing apparatus can be installed and dismantled within the handling areas. Accordingly, through replacement and arrangement performed by installing or dismantling the processing apparatus, the manufacturing line can be customized flexibly and various customer needs can be satisfied. Thus, the fully automatic gravure preparation processing system has high degrees of freedom. Conventionally, the stacker crane has been installed, and hence there is a limit to the location of the manufacturing line and the installation places of the processing apparatus. In contrast, according to the present invention, the processing apparatus only need to be installed within the handling areas of the first industrial robot and the second industrial robot, and hence there is such an advantage that the manufacturing line can be customized flexibly in response to the customer demands.
[0018] Further, it is preferred that: the processing room-A be arranged as a clean room; the processing room-A be provided with a roll entrance; the roll stock apparatus be arranged in the vicinity of the roll entrance so as to stock the roll to be prepared; the roll stock apparatus, the photosensitive film coating apparatus, the laser exposure latent image forming apparatus, the grinding wheel polishing apparatus, and the paper polishing apparatus be arranged within the handling area of the first industrial robot of the processing room-A; the degreasing apparatus, the ultrasonic cleaning apparatus, the copper plating apparatus, the surface hardening film forming apparatus, the developing apparatus, the etching apparatus, and the resist image removal apparatus be arranged within the handling area of the second industrial robot of the processing room-B; the processing room-A or the processing room-B include a roll transfer placement table; and the first industrial robot and the second industrial robot be configured to transfer the roll to be prepared therebetween via the roll transfer placement table when the preparation processing is performed.
[0019] It is preferred that the surface hardening film forming apparatus be a chromium plating apparatus, a DLC film forming apparatus, or a silicon dioxide film forming apparatus. For example, the diamond-like carbon (DLC) film forming apparatus for forming a DLC film as described in Patent Document 2, the silicon dioxide film forming apparatus for forming a silicon dioxide film as described in Patent Document 3, or the chromium plating apparatus as described in Patent Document 1 is applicable.
Advantageous Effects of Invention
[0020] The present invention produces a remarkable effect that it becomes possible to provide a fully automatic gravure preparation processing system having high degrees of freedom, which is capable of manufacturing a gravure printing roll more quickly as compared to a conventional case, achieving space saving, performing an unattended operation even in the nighttime, flexibly customizing a manufacturing line, and satisfying various customer needs.
BRIEF DESCRIPTION OF DRAWINGS
[0021] [ FIG. 1 ] A schematic plan view illustrating a fully automatic gravure preparation processing system according to an embodiment of the present invention.
DESCRIPTION OF EMBODIMENTS
[0022] Embodiments of the present invention are described below, but those embodiments are described as examples, and hence it is understood that various modifications may be made thereto without departing from the technical spirit of the present invention.
[0023] A fully automatic gravure preparation processing system for a gravure printing roll according to the present invention is described with reference to the accompanying drawing. In FIG. 1 , reference symbol 10 represents the fully automatic gravure preparation processing system for a gravure printing roll according to the present invention. The fully automatic gravure preparation processing system 10 includes a processing room-A and a processing room-B. The processing room-A and the processing room-B are partitioned by a wall 12 , and are communicable to each other via an openable and closable shutter 14 .
[0024] A configuration of the processing room-A is described. In the processing room-A, reference symbol 16 represents a first industrial robot, which includes a turnable multi-axis robotic arm 18 . The first industrial robot 16 is controlled by operating a control panel 28 . Reference symbol Q represents a turnable range of the robotic arm 18 , which corresponds to a handling area of the first industrial robot 16 .
[0025] Reference symbol 20 represents a roll to be prepared, and reference symbols 22 a and 22 b represent roll stock apparatus, respectively. As the roll stock apparatus, for example, the roll stock apparatus disclosed in Patent Documents 4 to 6 may be used.
[0026] Reference symbol 24 represents a photosensitive film coating apparatus, and reference symbol 26 represents a laser exposure apparatus. In the example of FIG. 1 , the photosensitive film coating apparatus 24 is provided above the laser exposure apparatus 26 . As those apparatus, conventionally known apparatus are applicable, and for example, the photosensitive film coating apparatus and the laser exposure apparatus as disclosed in Patent Documents 4 to 6 may be used. Reference symbol 50 represents a roll transfer placement table, on which the roll 20 to be prepared is placeable for transfer. Below the roll transfer placement table 50 , a paper polishing apparatus 21 is provided so as to perform paper polishing. As the paper polishing apparatus 21 , for example, the paper polishing apparatus as disclosed in Patent Documents 4 to 6 may be used. Further, in the processing room-A, a main control panel 52 is provided so as to control the fully automatic gravure preparation processing system 10 .
[0027] In the example of FIG. 1 , there is described a case where the photosensitive film coating apparatus 24 is installed and the laser exposure apparatus 26 performs laser exposure, but there may be employed a method in which an electronic engraving apparatus is installed so as to perform electronic engraving. As the electronic engraving apparatus, a conventionally known apparatus is applicable, and for example, the electronic engraving apparatus as disclosed in Patent Documents 4 to 6 may be used.
[0028] Next, a configuration of the processing room-B is described. In the processing room-B, reference symbol 30 represents a second industrial robot, which includes a turnable multi-axis robotic arm 32 . The second industrial robot 30 is controlled by operating a control panel 29 . Reference symbol P represents a turnable range of the robotic arm 32 , which corresponds to a handling area of the second industrial robot 30 .
[0029] Reference symbol 34 represents a grinding wheel polishing apparatus, and reference symbol 36 represents an ultrasonic cleaning apparatus. As the grinding wheel polishing apparatus 34 , a conventionally known apparatus is applicable, and for example, the grinding wheel polishing apparatus as disclosed in Patent Documents 4 to 6 may be used. Further, the ultrasonic cleaning apparatus 36 includes a reservoir for storing cleaning water, and an ultrasonic transducer provided below the reservoir. The ultrasonic cleaning apparatus 36 is capable of performing cleaning by vibrating the cleaning water through ultrasonic vibration of the ultrasonic transducer.
[0030] Reference symbol 38 represents a degreasing apparatus, and reference symbol 40 represents a copper plating apparatus. As those apparatus, conventionally known apparatus are applicable, and for example, the degreasing apparatus and the copper plating apparatus as disclosed in Patent Documents 4 to 6 may be used.
[0031] Reference symbol 42 represents a developing apparatus, and reference symbol 44 represents an etching apparatus. As those apparatus, conventionally known apparatus are applicable, and for example, the developing apparatus and the etching apparatus as disclosed in Patent Documents 4 to 6 may be used.
[0032] Reference symbol 46 represents a resist removal apparatus, and reference symbol 48 represents a chromium plating apparatus. As the resist removal apparatus, a conventionally known apparatus is applicable, and for example, the resist removal apparatus as disclosed in Patent Documents 4 to 6 may be used. As the chromium plating apparatus, a conventionally known apparatus may be used, and for example, the chromium plating apparatus as disclosed in Patent Document 1 may be used. Further, in the example of FIG. 1 , the chromium plating apparatus is used as an example of a surface hardening film forming apparatus, but alternatively, a DLC film forming apparatus or a silicon dioxide film forming apparatus is applicable as the surface hardening film forming apparatus. As the DLC film forming apparatus, for example, the DLC film forming apparatus as described in Patent Document 2 may be used, and as the silicon dioxide film forming apparatus, for example, the silicon dioxide film forming apparatus as described in Patent Document 3 may be used.
[0033] Reference symbol 70 represents a washing and drying apparatus, which is configured to perform washing and drying for each processing as necessary.
[0034] In the example of FIG. 1 , the processing room-A is arranged as a clean room. The processing room-A and the processing room-B may be arranged as clean rooms, respectively, as necessary.
[0035] Doors 58 and 60 are provided on a wall 56 of the processing room-A, through which a prepared roll is carried outside and a roll to be prepared (printing base material) is newly carried inside. The prepared roll is placed on any one of the roll stock apparatus 22 a and 22 b, and the roll to be prepared is placed on the other roll stock apparatus. A computer 62 is installed outside the processing room-A so as to check and manage various kinds of information, perform settings for various kinds of programs, and perform other operations. Reference symbol 64 represents a prepared roll that is manufactured.
[0036] Referring to FIG. 1 , actions of the fully automatic gravure preparation processing system according to the present invention are described. The first industrial robot 16 chucks the roll 20 to be prepared, which is placed on any one of the roll stock apparatus 22 a and 22 b, and places the roll 20 to be prepared on the roll transfer placement table 50 so that the roll 20 to be prepared is transferred to the second industrial robot 30 . The second industrial robot 30 chucks the roll 20 to be prepared, and transports the roll 20 to be prepared to the degreasing apparatus 38 . Then, the second industrial robot 30 releases the roll 20 to be prepared, and sets the roll 20 to be prepared onto the degreasing apparatus 38 .
[0037] When a degreasing work is finished at the degreasing apparatus 38 , the second industrial robot 30 chucks the roll 20 to be prepared, and transports the roll 20 to be prepared to the copper plating apparatus 40 . Then, the second industrial robot 30 releases the roll 20 to be prepared, and sets the roll 20 to be prepared onto the copper plating apparatus 40 .
[0038] When a plating work is finished at the copper plating apparatus 40 , the second industrial robot 30 chucks the roll 20 to be prepared, and transports and places the roll 20 to be prepared onto the roll transfer placement table 50 so that the roll 20 to be prepared is transferred to the first industrial robot 16 . The first industrial robot 16 chucks the roll 20 to be prepared, and transports the roll 20 to be prepared to the grinding wheel polishing apparatus 34 . Then, the first industrial robot 16 releases the roll 20 to be prepared, and sets the roll 20 to be prepared onto the grinding wheel polishing apparatus 34 .
[0039] When a grinding wheel polishing work is finished at the grinding wheel polishing apparatus 34 , the first industrial robot 16 chucks the roll 20 to be prepared, and transports the roll 20 to be prepared to the ultrasonic cleaning apparatus 36 . Then, the first industrial robot 16 releases the roll 20 to be prepared, and sets the roll 20 to be prepared onto the ultrasonic cleaning apparatus 36 .
[0040] When an ultrasonic cleaning work is finished at the ultrasonic cleaning apparatus 36 , the first industrial robot 16 chucks the roll 20 to be prepared, and transports the roll 20 to be prepared to the photosensitive film coating apparatus 24 . Then, the first industrial robot 16 releases the roll 20 to be prepared, and sets the roll 20 to be prepared onto the photosensitive film coating apparatus 24 .
[0041] When a photosensitive film coating work is finished at the photosensitive film coating apparatus 24 , the first industrial robot 16 chucks the roll 20 to be prepared, and transports the roll 20 to be prepared to the laser exposure apparatus 26 . Then, the first industrial robot 16 releases the roll 20 to be prepared, and sets the roll 20 to be prepared onto the laser exposure apparatus 26 .
[0042] When a laser exposure work is finished at the laser exposure apparatus 26 , the first industrial robot 16 chucks the roll 20 to be prepared, and places the roll 20 to be prepared onto the roll transfer placement table 50 so that the roll 20 to be prepared is transferred to the second industrial robot 30 . The second industrial robot 30 chucks the roll 20 to be prepared, and transports the roll 20 to be prepared to the developing apparatus 42 . Then, the second industrial robot 30 releases the roll 20 to be prepared, and sets the roll 20 to be prepared onto the developing apparatus 42 .
[0043] When a developing work is finished at the developing apparatus 42 , the second industrial robot 30 chucks the roll 20 to be prepared, and transports the roll 20 to be prepared to the etching apparatus 44 . Then, the second industrial robot 30 releases the roll 20 to be prepared, and sets the roll 20 to be prepared onto the etching apparatus 44 .
[0044] When an etching work is finished at the etching apparatus 44 , the second industrial robot 30 chucks the roll 20 to be prepared, and transports the roll 20 to be prepared to the resist removal apparatus 46 . Then, the second industrial robot 30 releases the roll 20 to be prepared, and sets the roll 20 to be prepared onto the resist removal apparatus 46 .
[0045] When a resist removal work is finished at the resist removal apparatus 46 , the second industrial robot 30 chucks the roll 20 to be prepared, and transports the roll 20 to be prepared to the chromium plating apparatus 48 . Then, the second industrial robot 30 releases the roll 20 to be prepared, and sets the roll 20 to be prepared onto the chromium plating apparatus 48 . Then, chromium plating is performed at the chromium plating apparatus 48 . Note that, the roll 20 to be prepared is washed and dried for each processing at the washing and drying apparatus 70 .
[0046] When a plating work is finished at the chromium plating apparatus 48 , the second industrial robot 30 chucks the roll 20 to be prepared, and transports the roll 20 to be prepared to the paper polishing apparatus 21 . Then, the second industrial robot 30 releases the roll 20 to be prepared, and sets the roll 20 to be prepared onto the paper polishing apparatus 21 . When paper polishing (automatic polishing) is performed at the paper polishing apparatus 21 , the prepared roll 64 is obtained and, in the example of FIG. 1 , placed on the roll stock apparatus 22 b.
[0047] The prepared roll 64 thus obtained is carried outside the processing room-A as a final product.
[0048] Note that, the above-mentioned actions are an example of the fully automatic gravure preparation processing system according to the present invention, and the manufacturing line can be customized flexibly in response to customer needs so as to be constructed as a preparation line of various arrangements.
[0049] In the example of FIG. 1 , as each of the first industrial robot 16 and the second industrial robot 30 , the industrial robot as disclosed in Patent Documents 1 to 6 is used for transporting the roll 20 to be prepared to each processing apparatus, and releasing and setting the roll 20 to be prepared onto the processing apparatus. Then, the roll to be prepared is rotated by drive means provided in the processing apparatus.
[0050] On the other hand, there may be employed the following configuration. That is, as each of the first industrial robot and the second industrial robot, the industrial robot including drive means as disclosed in Patent Document 7 is used for transporting the roll 20 to be prepared to each processing apparatus, and setting the roll 20 to be prepared onto the processing apparatus while gripping the roll 20 to be prepared. Then, the roll to be prepared is rotated by the drive means provided in the industrial robot.
REFERENCE SIGNS LIST
[0051] 10 : fully automatic gravure preparation processing system, 12 : wall, 14 : shutter, 16 : first industrial robot, 18 , 32 : robotic arm, 20 : roll to be prepared, 21 : paper polishing apparatus, 22 a, 22 b: roll stock apparatus, 24 : photosensitive film coating apparatus, 26 : laser exposure apparatus, 28 , 29 : control panel, 30 : second industrial robot, 34 : grinding wheel polishing apparatus, 36 : ultrasonic cleaning apparatus, 38 : degreasing apparatus, 40 : copper plating apparatus, 42 : developing apparatus, 44 : etching apparatus, 46 : resist removal apparatus, 48 : chromium plating apparatus, 50 : roll transfer placement table, 52 : main control panel, 56 : wall, 58 , 60 : door, 62 : computer, 64 : prepared roll, 70 : washing and drying apparatus, A: processing room, B: processing room, P, Q: turnable range. | Provided is a fully automatic gravure preparation processing system having high degrees of freedom, which is capable of manufacturing a gravure printing roll more quickly as compared to a conventional case, achieving space saving, performing an unattended operation even in the nighttime, flexibly customizing a manufacturing line, and satisfying various customer needs. The fully automatic gravure preparation processing system includes: a processing room-A having a handling area of a first industrial robot for chucking and handling a roll to be prepared; and a processing room-B having a handling area of a second industrial robot for chucking and handling the roll to be prepared. The first industrial robot and the second industrial robot are configured to transfer the roll to be prepared therebetween when preparation processing is performed. | 1 |
CROSS-REFERENCE TO RELATED APPLICATION
This application claims the benefit of U.S. provisional application No. 61/878,901 filed Sep. 17, 2014. The aforementioned application is incorporated by reference in its entirety.
BACKGROUND
The present invention relates to an improved shroud for mounting an accessory device to headgear. The shroud described herein may advantageously be used in connection with mounting assemblies for attaching night vision devices and will be described herein primarily by way of reference thereto. However, it will be recognized that the shroud herein may be used with all manner of helmet or other headgear mounted accessories devices.
Night vision devices are used by military personnel, law enforcement personnel, and so forth when conducting military or tactical operations at night or under other low light conditions. Commonly, a mounting system is employed on the front of the user's headgear, such as a field helmet, to provide hands free support of the night vision device in front of the eyes of the user. Such mounting systems typically provide vertical, lateral, fore-and-aft, and tilt adjustment mechanisms for alignment of an attached night vision device with the eye or in the case of a binocular device eyes of the user. Mounting systems are known which allow the user to pivot the night vision device up to a stowed position out of the user's line of sight when not in use without removing the night vision device from the helmet.
Although mounting assemblies are known that allow the user to pivot the night vision device out of the way when the night vision device is not in use, it is often desirable to completely remove the night vision system and the mounting system from the headgear, e.g., during the daytime, in order to reduce helmet weight and strain on the user's neck, when entanglement hazards exist, etc. Commonly, night vision mounting systems are made removably attachable to a helmet through the use of a mounting bracket or shroud, as described, for example, in commonly owned U.S. Pat. No. 7,219,370. Such shrouds attach to the headgear with threaded fasteners using one or more holes drilled through the helmet. Standardized hole patterns have been developed, such as the Army-compatible single hole pattern and the MARSOC/WARCOM three-hole pattern. The use of standard hole patterns allow helmets to be pre-drilled to accept any shroud compatible with that hole pattern.
Typically, such helmet shrouds are machined using aluminum or other metal and include a receptacle for removable attachment of the mounting assembly. It has been found, however, that the manufacturing tolerances of the prior art shrouds are such that there is generally some clearance between the receptacle of the shroud and the interfacing portion of the mounting system, which results in a small amount of movement or play between the shroud and the mounting assembly. If has also been found that the process of repeated removal and attachment of the night vision mount creates wear, resulting in greater clearance and play between the shroud and the mounting assembly.
The present disclosure contemplates a new and improved shroud assembly that overcomes the above-referenced problems and others.
SUMMARY
In one aspect, a shroud assembly for headgear includes a frame which may be formed of a polymer material and having a shape that matches a contour of the headgear. An insert is formed of a metal or metal alloy and is attached to a front side of the frame. The insert is configured for removable attachment to a mounting assembly. The frame includes first and second spaced flexible walls disposed on the front side of the frame on opposite sides of the insert. The first and second flexible walls are spaced a distance apart so as to provide an interference fit between the mounting assembly and the first and second flexible walls.
In another embodiment, the shroud assembly further includes a friction pad disposed on a rear surface of the frame for increasing friction between the shroud assembly and the headgear.
In another aspect, a method for attaching a mounting assembly to headgear includes providing a shroud assembly by attaching an insert formed of a metal or metal alloy attached to a front side of a frame. The insert is configured for removable attachment to the mounting assembly. In certain embodiments, the frame is formed of a polymer material and has a shape that matches a contour of the headgear. The insert is attached to the frame between first and second spaced flexible walls disposed on the front side of the frame on opposite sides of the insert. The first and second flexible walls are spaced a distance apart to provide an interference fit between the mounting assembly and the first and second flexible walls. The mounting assembly is removably attached to the insert.
One advantage of the present development resides in its ability to prevent relative movement or play between the mounting assembly and the shroud.
Another advantage of the present development is found in the weight reduction that is capable of being achieved by making a portion of the shroud assembly from a polymer material.
Still further advantages and benefits of the present invention will become apparent to those of ordinary skill in the art upon reading and understanding the following detailed description of the preferred embodiments.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention may take form in various components and arrangements of components, and in various steps and arrangements of steps. The drawings are only for purposes of illustrating preferred embodiments and are not to be construed as limiting the invention.
FIG. 1 illustrates a shroud according to a first exemplary embodiment, attached to a helmet.
FIG. 2 is an enlarged isometric view of the shroud appearing in FIG. 1 .
FIG. 3 is an exploded view of the shroud appearing in FIG. 1 .
FIG. 4 illustrates the shroud embodiment of FIG. 1 with a night vision mount removably attached.
FIG. 5 illustrates the shroud embodiment of FIG. 1 with the night vision mount removed.
FIG. 6 is a front elevational view of the shroud embodiment of FIG. 1 .
FIG. 7 is a left side elevational view of the shroud embodiment of FIG. 1 , the right side view being a mirror image thereof.
FIG. 8 is a rear elevational view of the shroud embodiment of FIG. 1 .
FIG. 9 illustrates a shroud according to a second exemplary embodiment, attached to a helmet.
FIG. 10 is an enlarged isometric view of the shroud appearing in FIG. 9 .
FIG. 11 is an exploded view of the shroud appearing in FIG. 9 .
FIG. 12 is a front elevational view of the shroud embodiment of FIG. 9 .
FIG. 13 is a left side elevational view of the shroud embodiment of FIG. 9 , the right side view being a mirror image thereof.
FIG. 14 is a rear elevational view of the shroud embodiment of FIG. 9 .
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring now to the drawings, FIGS. 1-8 illustrate a first embodiment shroud assembly 110 for attachment to the front of a helmet 112 . For the sake of brevity, the present shroud assembly will be described herein primarily by way of reference to use with night vision systems. However, it will be recognized that the present shroud assembly is also amenable for use with all manner of monocular and binocular devices, including optical viewing devices, thermal cameras, head up displays, virtual reality goggles, or other electronic or optoelectronic imaging devices.
The shroud assembly 110 includes a frame, e.g., a polymer frame 114 , a metal or metal alloy insert 116 , and a natural or synthetic elastomeric pad 118 . The shroud assembly 110 is primarily intended for use in connection with a helmet 112 having a single mounting hole, such as the standard U.S. Army one-hole mounting pattern, and will be described primarily by way of reference thereto. It will be recognized, however, that the shroud assembly 110 could likewise be used with or without the elastomeric backing pad 118 with a helmet having holes drilled in a three hole mounting pattern, such as the standard MARSOC/WARCOM three-hole pattern, in the same manner as detailed below in connection with the shroud assembly 210 .
The shroud assembly 110 provides an interface for the removable attachment of a night vision mounting system 120 . The mounting system may be, for example, a night vision mounting system in the L 4 product line available from Wilcox Industries Corp. of Newington, N.H. It will be recognized that the present shroud assembly can be adapted for use with all manner of night vision mounting systems by providing an insert 116 which has retention features complimentary with a desired night vision mounting system. In certain embodiments, the polymer frame may be provided with a plurality of interchangeable metal inserts to provide a modular system capable of being used with multiple mounting systems.
The frame 114 and the friction pad 118 have a generally concave rearward surface which is shaped to generally conform to the shape of the helmet 112 . The elastomeric pad 118 may be formed of natural or synthetic rubber or other elastomer. The pad 118 increases the friction between the shroud assembly 110 and the helmet 112 and is particularly advantageous for use with a helmet 112 having a one hole pattern to prevent rotation about fasteners 124 , 130 which secure the shroud assembly 110 to the helmet 112 .
The insert 116 is preferably formed by machining although cast or molded inserts 116 are also contemplated. The insert 116 is preferably formed of aluminum or aluminum alloy. In the illustrated preferred embodiment, the insert 116 includes an opening 122 for receiving a threaded fastener 124 . The opening 122 may be elongated in the vertical direction to provide vertical adjustability when mounting the assembly 110 , e.g., to accommodate differences between the drilled hole placement on the helmet, accommodate edge trim on the brim of the helmet, and so forth.
The threaded fastener passes through the hole 122 , a large central opening 126 in the polymer frame 114 , a large central opening 128 in the elastomeric pad 118 , and a hole (not shown) in the helmet 112 . The fastener 124 is secured to a complementary threaded fastener 130 on the inside of the helmet 112 .
The insert 116 includes features, such as upper and lower recesses 132 , 134 , respectively, for removably engaging latch members 133 formed on the mounting system 120 . The insert 116 is received within a like sized cavity 136 on the composite member 114 . One or more fasteners, such as threaded fasteners 138 secure the insert 116 within the cavity 136 via openings 140 in the insert 116 and openings 142 in the frame 114 . Other fasteners, such as other types of mechanical fasteners or adhesives are also contemplated.
In certain embodiments, the frame 114 may be formed of an injection moldable plastic, such as a thermoplastic resin, although thermosetting polymers are also contemplated. In preferred embodiments, the frame 114 is formed of a fiber reinforced polymer matrix composite material, although other materials are contemplated. Reinforcing fibers for polymer matrix composite materials are generally known. Exemplary fibers include carbonaceous fibers (e.g., carbon or graphite fibers), glass fibers, and other filamentary materials. In an especially preferred embodiment, the frame 114 is formed of a 30% glass filled polyimide composite material.
A pair of flexible walls or blades 115 extends from the face of the polymer frame 114 immediately adjacent the cavity 136 on opposite lateral sides thereof. Because the blades 115 are formed of a polymer material, they can flex and can therefore be spaced apart a distance that provides a snug, interference fit between the blades 115 and the sides of an attached mounting system 120 . In this manner, side-to-side movement between the mounting system 120 and the shroud assembly 110 can be eliminated. This is in contrast to prior art metal shrouds which must be toleranced to provide a clearance fit between the shroud and the mounting system, allowing undesirable side-to-side movement between the shroud and the helmet mount. In addition, the use of a polymer frame 114 provides a reduction of the weight of the shroud assembly 110 as compared to prior art metal shrouds.
In the depicted preferred embodiment, the blades 115 include a tapered or angled surface 117 on the interior facing side thereof to facilitate insertion of the mounting system 120 and outward flexing of the blades 115 .
The depicted preferred embodiment illustrates an exemplary shroud assembly adapted for use with a mounting assembly that has latches that move or provide tension in the vertical direction, such that the blades 115 are disposed on opposite lateral sides of an attached mounting assembly. Other orientations of the blades, however, are also contemplated. For example, in the case of a mounting assembly having latch members that move and provide tensioning in a horizontal direction, the flexible blades could be oriented horizontally above and below the mounting assembly interfacing portion to eliminate up and down movement.
The frame 114 is of a generally triangular construction and includes three openings 144 at the corners. The friction pad 118 is shaped to receive the frame 114 on the outward facing surface of the friction pad 118 in a stacked or nested arrangement. The pad 118 includes three openings 146 at the corners aligned with the openings 144 at the corners of the frame 114 . The pad 118 further includes three bosses or protrusions 148 , which are disposed intermediate the central opening 128 and the openings 146 . When the frame 114 and the friction pad 118 are stacked in the assembled, nested configuration, the bosses 148 extend through aligned openings 150 in the frame 114 , to interlock the frame 114 and the pad 118 together. The frame 114 and pad 118 are further secured via three plugs 152 at the corners of the unit 110 . Each plug 152 includes a base 154 which is received in one of the openings 146 in the pad 118 . Each plug 152 further includes a protrusion 156 that extends through a corresponding one of the openings 144 in the frame 114 .
In alternative embodiments, the plugs 152 can be omitted, as well as the central helmet fasteners 124 , 130 and the unit 110 can be secured to a helmet having a three-hole pattern. The helmet drill/hole pattern may advantageously be the standard MARSOC/WARCOM three-hole pattern. It will be recognized that the unit 110 could also be attached to a helmet using both the central hole via the fasteners 124 , 130 as well as three threaded fasteners (see e.g., fasteners 245 , 247 appearing in FIG. 11 ) using the openings 144 ; however, in general, it is preferable to use only the one hole pattern or the three hole pattern, since unnecessary holes drilled into the helmet can compromise the ballistic integrity of the helmet.
Referring now to FIGS. 9-14 , a second embodiment shroud assembly 210 for attachment to the front of a helmet 212 is illustrated. The shroud assembly 210 is similar to the embodiment 110 described above, however, the friction pad is omitted.
The shroud assembly 210 includes a polymer frame 214 and a metal or metal alloy insert 216 . Because the should assembly 210 is intended for use with a three hole pattern, the insert 216 need not include the central fastening hole 122 . The insert 216 may be formed by machining aluminum or an aluminum alloy. In the illustrated preferred embodiment, an enlarged central opening 223 is provided in the insert 216 to reduce the weight of the assembly, thereby reducing overall weight on the user's neck. However, the insert 216 otherwise interfaces with the mounting assembly in the manner as described above.
The mounting features of the insert 216 may be modified depending on the particular helmet mounting system to be employed. A modular system may also be provided wherein multiple metal inserts 216 are interchangeable to provide a system capable of being used with multiple mounting systems.
The insert 216 includes features, such as upper and lower recesses 232 , 234 , respectively, for removably engaging complementary latch members 133 (see FIG. 5 ) on the mounting system. The insert 216 is received within a like sized cavity 236 formed on the composite member 214 . One or more fasteners, such as threaded fasteners 238 secure the insert 216 within the cavity 236 via openings 240 in the insert 216 and openings 242 in the frame 214 . Other fasteners such other mechanical fasteners or adhesives are also contemplated.
The polymer frame 214 may be formed of an injection moldable plastic, and may be formed of the same materials as described above by way of reference to the frame 114 (see FIGS. 1-8 )
A pair of flexible walls or blades 215 extends from the face of the polymer frame 214 immediately adjacent the cavity 236 on opposite lateral sides thereof. Because the blades 215 can flex, the blades can be spaced apart a distance that provides a snug, interference fit between the blades 215 and the sides of the mounting system 120 (see FIGS. 4 and 5 ). In this manner, side-to-side movement between the mounting system and the shroud assembly 210 can be eliminated. In the depicted preferred embodiment, the blades 215 include an angled or tapered surface 217 on the interior facing side thereof to facilitate insertion of the mounting system 120 and outward flexing of the blades 215 . In reducing the present development to practice, it has been found that the present shroud continues to provide an interference fit between the shroud assembly and the mounting system even after insertion and removal of the mounting system more than 5,000 times. Again, vertically oriented blades are illustrated in the depicted embodiment, although other blade orientations are also contemplated.
The frame 214 is of a generally triangular construction and includes three openings 244 at the corners. Threaded fasteners 245 pass through the openings 244 and engage complementary threaded fasteners 247 passing through the helmet 212 to secure the shroud assembly to the helmet. The helmet drill/hole pattern may advantageously be the standard MARSOC/WARCOM three-hole pattern.
The invention has been described with reference to the preferred embodiment. Modifications and alterations will occur to others upon a reading and understanding of the preceding detailed description. It is intended that the invention be construed as including all such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof. | In one aspect, a shroud assembly for headgear includes a frame formed of a polymer material having a shape that matches a contour of the headgear. An insert is formed of metal or metal alloy and is attached to a front side of the frame. The insert is configured for removable attachment to a mounting assembly. The frame includes first and second spaced flexible walls disposed on the front side of the frame on opposite sides of the insert. The first and second flexible walls are spaced a sufficient distance apart to provide an interference fit between the mounting assembly and the first and second flexible walls. In another embodiment, the shroud assembly further includes a friction pad disposed on a rear surface of the frame for increasing friction between the shroud assembly and the headgear. In another aspect, a method for attaching a mounting assembly to headgear is provided. | 0 |
BACKGROUND OF THE INVENTION
[0001] The application of CT (Computed Tomography) in radiation therapy treatment planning has tremendously increased in recent years. Indeed, the CT information is essential in two aspects of treatment planning: a) delineation of target volume and the surrounding structures in relation to the external contour; and b) providing quantitative data, i.e. the attenuation coefficients converted into CT numbers in units of Hounsfield, for tissue heterogeneity corrections. For instance, in the treatment of prostate cancer, contouring the prostate and simulating the dose distribution are essential for planning. Meanwhile, the image artifacts produced by metal hip prostheses (see FIG. 1 ), referred as metal artifacts, make the planning extremely difficult. In any cases, prostheses must be avoided at the time of planning (TG63).
[0002] Metal artifacts are a significant problem in x-ray computed tomography. Metal artifacts arise because the attenuation coefficient of a metal in the range of diagnostic X-rays is much higher than that of soft tissues and bone. The results of scanning a metal object are gaps in CT projections. The reconstruction of gapped projections using standard CT reconstruction algorithms, i.e. filtered backprojection (FBP), causes the effect of bright and dark streaks in CT images ( FIG. 1 ). This effect significantly degrades the image quality in an extent that modern planning process cannot be applied.
[0003] Many different techniques have been proposed to reduce metal artifacts in literature. Some techniques suggested to replace the metal implants with less attenuating materials or to use higher energy x-ray beams for preventing metal artifacts. Others used image windowing techniques to reduce the appearance of artifacts in the images. However, these case-by-case solutions are not ideal for most clinical applications. The most efficient methods work on the raw projection data, i.e. the matrix of ray attenuations related to different angles acquired by the CT scanner. In iterative reconstruction methods, the projection data associated with metal objects are disregarded and reconstruction is applied only for non-corrupted data. Briefly, in these methods, an initial guess of the reconstructed image is made and then the projections obtained of this initial image are compared to the raw projection data. By iteratively reconstructing projection ratios and applying an appropriate correction algorithm for initial image, an improved estimate of the image is obtained. Although these algorithms are reliable for incomplete/noisy projection data, they must deal with convergence problems and they are computationally expensive for clinical CT scanners (even with their fast implementation). In projection interpolation based methods, the projection data corresponding to rays through the metal objects are considered as missing data. A prior art technique identified manually the missing projections and replaced them by interpolation of non-missing neighbor projections. A prior art technique used a linear prediction method to replace the missing projections. In other work, a polynomial interpolation technique is used to bridge the missing projections. A wavelet multiresolution analysis of projection data is also proposed to detect the missing data and interpolate them. Although these methods do not increase significantly the computational cost, they have achieved varying degrees of success and appear to depend on the complexity of the structures examined and may still result in artifacts in the final reconstruction.
[0004] A prior art technique uses another strategy for computing the interpolation value by the sum of weighted nearest not-affected projection values within a window centered by the missing projection. The weights are modeled only based on the distance. Although they exploit the contribution of not-affected projections in all directions to determine the replacement values, they do not preserve the continuity of the structure of these projections. Furthermore, because there is no continuity between resulting replacement values, the risk of noise production is also high. In a prior art technique, we used an optimization scheme exploiting both the distance and the value of not affected projections to determine the interpolation values and by using still an interpolation scheme to preserve the continuity of replacement values. This new scheme computed more effectively the interpolation values based on the structure of nearest not affected projections and resulted an excellent performance in the case of hip prosthesis.
[0005] Although the interpolation-based methods do not increase significantly the computational cost and achieve a good degree of success in image quality for the case of hip prosthesis, their performance is severely degraded in the presence of multiple and closed metallic objects such as dental fillings. Indeed, these methods are so sensitive to the correct detection of the missing projections. When multiple and closed metallic implants are present in the field of view of scanner, it is so difficult to exactly distinguish the missing projections due to each metallic objects by the sinogram. Consider the case of dental fillings ( FIG. 8 ). As we can see, because metallic objects are small with different shapes/sizes and placed near to each other, their detection becomes extremely difficult. Moreover, when the mouth is closed and a continuous scanning is done from head to feet, the structure of adjacent dental fillings from up-teeth to down-teeth changes suddenly which give rise to more difficulties for their detection. So, the interpolation-based methods have to consider a large region as missing projections in the sinogram to cover all metallic projections and then replace most relevant data by synthetic data. As a consequence, anatomic details between and surrounding the multiple metallic implants are totally missing. It arises more difficulties for radiation oncology where the quantitive analysis of CT images is essential for accurate structure contouring and dose calculation. Thus the needs to develop more sophisticated metal artefact reduction (MAR) algorithms especially for complex cases such as dental fillings.
[0006] A prior art technique proposes an adaptive filtering approach for MAR. First a tissue class model is created from initial CT image. Then a model sinogram is generated using this class and compared with original sinogram to identify and to replace missing projection. The difference between original and model sinograms is downscaled and then filtered adaptively. The corrected sinogram is used to regenerated the CT image. Although they used a more sophisticated approach for the metal detection step, their replacement scheme cannot achieve a good estimation of original values for the case of dental implants and resulted many false labellings near the metallic implants A prior art technique studies the metal artifacts in the wavelet domain especially for the case of dental fillings. Their approach consists of using a scale-level dependent of linear interpolation of wavelet coefficients of sinogram to reveal the corrupted data and a linear-interpolation scheme to replace missing projections. Although the use of wavelet domain aids to more implicitly detection of metal traces due to multiple metallic objects in the sinogram, their replacement scheme has still disadvantages of interpolation based methods. Moreover, an extremely delicate optimal selection of weight parameters for wavelet interpolation is required in this algorithm.
[0007] Our observation is that a most efficient replacement scheme can afford a more sophisticated metal artifact reduction method especially for the complex case of dental fillings. We propose a new replacement scheme to modify the sinogram containing the missing projections by searching the relevant replacement values in the opposite direction of original values, contrary to interpolation based scheme in which replacement values are computed artificially using nearest non-affected projections. Although this new replacement scheme is also based first on detecting of metallic objects, it is much less sensitive to this step. This approach is especially applicable in Head and Neck cases with metal implants such as dental fillings and produces significantly better quality CT images than interpolation-based MAR algorithms.
SUMMARY OF THE INVENTION
[0008] In an embodiment, the present invention provides a method for reducing artifacts in an original computed tomography (CT) image of a subject, the original (CT) image being produced from original sinogram data. The method comprises detecting an artifact creating object in the original CT image; re-projecting the artifact creating object in the original sinogram data to produce modified sinogram data in which missing projection data is absent; interpolating replacement data for the missing projection data; replacing the missing projection data in the original sinogram data with the interpolated replacement data to produce final sinogram data; and reconstructing a final CT image using the final sinogram data to thereby obtain an artifact-reduced CT image.
[0009] In an embodiment a CT scanner device capable of reducing artifacts in an original computed tomography (CT) image of a subject, the original (CT) image being produced from original sinogram data. The CT scanner comprising:
an X-ray source for providing X-rays; X-ray detectors for detecting the X-rays; a processing unit for producing the original CT image using the X-rays, the processing unit also for:
detecting an artifact creating object in the original CT image; re-projecting the artifact creating object in the original sinogram data to produce modified sinogram data in which missing projection data is absent; interpolating replacement data for the missing projection data; replacing the missing projection data in the original sinogram data with the interpolated replacement data to produce final sinogram data; and
reconstructing a final CT image using the final sinogram data to thereby obtain an artifact-reduced CT image.
[0018] An approach for metal artifact reduction is proposed that is practical for use in radiation therapy. It is based on interpolation of the projections associated with metal implants at helical CT (computed tomography) scanner. The present invention comprises an automatic algorithm for metal implant detection, a correction algorithm for helical projections, and a more efficient algorithm for projection interpolation. Moreover, this approach can be used clinically as complete modified raw projection data is transferred back to the CT scanner device where CT slices are regenerated using the built-in reconstruction operator. So, all detail information on scanner geometry and file format is preserved and no changes in routine practices are needed. The validations on a CT calibration phantom with various inserts of known densities prove the efficiency of the algorithm to improve the overall image quality and more importantly to preserve the form and the representative CT number of objects in the image. The results of application of the algorithm on prostate cancer patients with hip replacements demonstrate the significant improvement in image quality and allow a more precise treatment planning.
[0019] There are no automatic and robust algorithms for metal artifact reduction which can be practical for routine clinical applications. The goal of this work is to investigate a clinical approach to effectively improve the quality of the helical CT images in the presence of metal artifacts for treatment planning process. The approach is based on the projection interpolation because of its simplicity and speed. The results are presented for both phantom and patient images obtained with a Helical-CT scanner (Siemens, Somatom).
[0020] This approach has three main advantages; i) the algorithm can be used clinically as we currently use it as a pre-processing technique for prostate treatment planning; ii) the metal markers which are used for virtual simulation planning are also another source of artifacts with a much lower degree of importance and should not be eliminated from CT images. These markers can be easily distinguished from other metal objects and will be maintained for other processing; iii) virtual simulation is a tool for planning and designing radiation therapy treatment. Since the virtual simulation needs the parameters produced during the patient scanning, we transfer the modified projection data back to the scanner device and use its built-in reconstruction operators. Thus, the routine application will be the same and all detail information on scanner geometry and file format will be maintained.
[0021] This clinical approach for metal artifact reduction can be successfully applied for the therapy treatment planning. This technique brings three improvements to the conventional approaches for metal artifact reduction using projection interpolation scheme. These improvements are adapted to the clinical application. The proposed algorithm can be applied for helical and non-helical CT scanners. In both phantom experiment and patient studies, the algorithm resulted in significant artifact reduction with increases in the reliability of planning procedure for the case of metallic hip prostheses. This algorithm is currently used as a pre-processing for prostate planning treatment in presence of metal artifacts.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] These and other features, aspects and advantages of the present invention will become better understood with regard to the following description and accompanying drawings wherein:
[0023] FIG. 1 shows an example of artifacts produced by scanning a patient with two hip prostheses using a prior art Siemens Somatom scanner;
[0024] FIG. 2 . shows an example of missing projection detection; (a) raw projection data, (b) initial reconstructed image, (c) metal object segmentation, (d) case of using markers, (e) markers in the exterior of patient body contour, (f) missing projections in raw projection data;
[0025] FIG. 3 shows an example of missing projection correction for helical projection; (a) intensity profile at a given angle, (b) initial contouring of the missing projections, (c) final contouring of the missing projections, (d) gradient curve of the intensity profile in FIG. 3( a ), ( e ) zooming the block in FIG. 3( b ), ( f ) zooming the block in FIG. 3( c );
[0026] FIG. 4 shows the results of the adaptive interpolation algorithm; (a) raw projection data and missing projections (black region), (b) result of applying the interpolation on each given angle (i.e. vertical lines), (c) artifact result of this interpolation scheme, (d) result of applying the adaptive interpolation, (e) reduction of artifacts in the reconstructed image;
[0027] FIG. 5 shows a phantom test; (a) original phantom image without inserting metallic rods, (b) presence of artifacts because of metallic rods, (c) result of artifact reduction algorithm, (d) result of applying an automatic edge detection algorithm on original phantom image, (e) on phantom image with metallic rods, (f) on artifact reduction image, (g) computing the mean and standard deviation for three objects in the middle of the phantom in original phantom image, (h) in phantom image with metallic rods, and (i) in artifact reduction image;
[0028] FIG. 6 shows a patient test; (a) Topogram of a patient with two hip prostheses, (b) reconstructed image using the Siemens Somatom scanner, (c) result of applying the metal artifact reduction algorithm;
[0029] FIG. 7 shows the DRR results; (a) Original case with two hip prostheses, (b) after applying the metal artifact reduction algorithm, (c) after overriding the prostheses information into the result of metal artifact reduction; and
[0030] FIG. 8 shows another example of artifacts produced by scanning a patient with dental implants using a Siemens Somatom scanner;
[0031] FIG. 9 shows an embodiment of the procedure of missing projections detection; a) original sinogram, b) reconstructed CT image, c) metallic object detection, d) reprojection of metallic objects into the sinogram. Black areas are detected missing projections;
[0032] FIG. 10 shows the geometry of an equiangular fan-beam. All angles are positive as shown;
[0033] FIG. 11 shows the geometry of opposite angular positions;
[0034] FIG. 12 shows the projections and their opposite sides in the sinogram;
[0035] FIG. 13 shows a sinogram replacement scheme strategy according to an embodiment. The black area is missing projections. A′B′ and C′D′ are the opposite sides of AB and CD respectively. Arrows show the directions of replacing sheme;
[0036] FIG. 14 shows an example of a topogram for a patient with dental fillings;
[0037] FIG. 15 shows a sinogram of a patient (human) scanned by a Siemens Somatom scanner;
[0038] FIG. 16 shows a CT image sequence reconstructed using the sinogram of FIG. 15 ;
[0039] FIG. 17 shows a modified sinogram (also referred to herein as final sinogram) using the replacement scheme;
[0040] FIG. 18 shows a CT image sequence reconstructed using the modified sinogram of FIG. 17 where CT images have the same level of contrast as those in FIG. 16 ; and
[0041] FIG. 19 shows a comparison of the proposed approach with interpolation-based method; a) original CT image, b) result of applying interpolation based method, c) result of applying the proposed approach.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Method and Materials
[0042] In a first example, the algorithm is based on the interpolation of missing projections in raw projection data. The modified projection data is used to generate slice images by scanner standard reconstruction algorithm. No further modification in the employed operators is required for this reconstruction. The resulting tomographies are still subject to minor artifact in the area near to the boundary of metal implants, but there are significant gains in image quality for regions of interest such as prostate.
[0043] Three extensions are introduced: the first step is to detect the projections affected by metal implants. Some authors proposed to isolate the correspondence of the metal implants directly from the projection, but have difficulties to fix the appropriate thresholds because of the complex structure of the projection data. Others are identifying the sinusoidal curves resulting from metal implant in the projection data. Although these approaches are interesting, they still need to fix some parameters and studies are limited to parallel projections. In this algorithm, the metal prostheses are identified quasi-automatically from reconstructed images. First, we reconstruct an initial image from the 360 degrees raw helical projection data using fan-beam FBP (see FIGS. 2( a ) and 2 ( b )). Since the metal objects produce high-value-connected pixels in the initial image, a fixed fraction of the maximum value found in the initial image is used as the threshold for detecting the metal objects (see FIG. 2( c )). In this way, the threshold will be automatically determined in each reconstructed image. The metal markers are routinely used at exterior of patient body as reference points for planning procedure and should be preserved. They can be easily distinguished from metal implants in the initial image. To do so, the exterior contour of the patient body is detected in the initial image (see FIGS. 2( d ) and 2 ( e )) and all metal objects on this contour are considered as markers which will be used for virtual simulation. Finally, the metal implant regions in the initial image are reprojected using a fan-beam projection algorithm to obtain approximate missing projections in the raw projection data (the black areas in FIG. 2( f )). These missing projections are next replaced by synthetic data using an interpolation scheme. Another example of the missing projection detection is shown in FIGS. 9 a ) to 9 d ).
[0044] In helical scanning, the patient is transported continuously as the tube and detector rotate around the patient. So, during one rotation (360 degrees) of tube, the patient may be translated from 1 mm to 10 mm for typical procedures. In this interval, the metallic prostheses may change orientation or undergo a deformation. To precisely detect the missing projections in helical raw projection data, we make a correction for reprojected metal implant regions adapted to these changes. FIG. 3( a ) shows a vertical intensity profile at a given angle through the metal trace in FIGS. 3( b ) and 3 ( e ). Plotted on the y-axis is the projection intensities as a function of position (x-axis). As we can see the peak represents the projection of metallic implant at this given angle. To precisely determine the projected edges, we compute its gradient curve ( FIG. 3( d )). The first peak and the last peak in this curve represent the projected edges and consequently the missing projections over which interpolation needs to be applied. We continue this step for all vertical lines in projection data to correctly determine the missing projections. FIGS. 3( c ) and 3 ( f ) show the results for corrected reprojected metal implant regions.
[0045] In conventional algorithms for replacing the missing projection, an interpolation scheme is generally applied using the projected edges for the same view angle. Although this strategy reduced the artifacts due to metal objects, the resulting tomographies are still subject to additional artifacts. Indeed, these additional artifacts are due to the destruction of boundary of other objects in the area of interpolated projections. FIGS. 4( a ), 4 ( b ), and 4 ( c ) show an example of this situation and its resulting additional artifact. Based on this observation, a more efficient algorithm was used to preserve the structure of adjacent projections during the interpolation. The idea is to apply the interpolation scheme between the two corresponding projected edges belonging to the projection regions of the same object. To do this, a set (m) of projected edges is determined on one side of a reprojected metal implant region and another set (n) is determined for other side of this region using the algorithm presented in step 2. Then for each projected edge belonging to m, we find the corresponding projected edge in n so that their distance and difference values are minimized. Let pixels P k (k belongs to m) and P j (j belongs to n) be the projected edges. We defined the function D as the distance between P k and P j :
[0000]
D
(
P
k
,
P
j
)
=
(
x
p
k
-
x
p
j
)
2
-
(
y
p
k
-
y
p
j
)
2
,
(
1
)
[0000] where x and y are the coordinates of a projected edge in the sinogram. Because the difference of only two projected edges is not reliable to determine that they belong to the same object, we select a group of adjacent projected edges around them to define the function of difference values V:
[0000]
V
(
P
k
,
P
j
)
=
∑
i
I
P
k
+
i
-
I
P
j
+
i
,
i
=
-
N
,
…
,
N
(
2
)
[0000] where I is the intensity value of a projected edge and N is the size of the group surrounding each projected edge (in this case N=2).
[0046] This goal is to find for each P k the best P j that optimizes simultaneously these functions. This type of problem is known as either a multiobjective, multicriteria, or a vector optimization problem. Many techniques have been proposed to solve this problem. We applied a min-max optimization method using Eq. (1) and Eq. (2) to determine the corresponding projected edges in both sides of the reprojected metal implant regions. Finally, we use a linear interpolation between these two corresponding projected edges to replace the projections in the metal implant regions. We continue this for all set of projected edges. Finally, we apply a median filter (size of 5×5 pixels) to remove the isolated high value projections which may not be interpolated in metal implant regions. FIGS. 4( d ) and 4 ( e ) show the results in projection data and reconstructed image. As it can be seen, the continuity of boundary structures in the area of interpolated projections is maintained and the additional artifact is removed.
[0047] These steps are repeated for all raw projection data to remove and interpolate the projections affected by the implants. In a last step, the whole modified raw projection data is transferred back to reconstruction operator of CT scanner to regenerate slice images.
[0048] In a second example, the algorithm is based on replacing missing projections in sinogram by their unaffected correspondences in opposite direction. The modified sinogram is used to regenerate slice images by scanner standard reconstruction algorithm. No further modification in the employed operators is required for this reconstruction. The resulting tomographies by the proposed approach show significant improvements in image quality, especially for regions near the metallic implants, compared to those by interpolation-based approaches. In this work, we describe the algorithm for a helical scanner which is based on spiral projections. It is obvious that the extension of this work for a parallel projection will be trivial. The approach is composed of three steps.
Step 1: Missing Projection Detection
[0049] First step is to detect the projections affected by metal implants. Some authors proposed to isolate the correspondence of the metal implants directly from the projection, but have difficulties to fix the appropriate thresholds because of the complex structure of the projection data. Others are identifying the sinusoidal curves resulting from metal implant in the projection data. Although these approaches are interesting, they still need to fix some parameters and studies are limited to parallel projections. In our algorithm, the metal objects are identified quasi-automatically from reconstructed images. First, we reconstruct an initial image from the 360 degrees raw helical projection data using fan-beam FBP (see FIGS. 9( a ) and 9 ( b )). Since the metal objects produce high-value-connected pixels in the initial image, a fixed fraction of the maximum value found in the initial image is used as the threshold for detecting the metal objects (see FIG. 9( c )). In this way, the threshold will be automatically determined in each reconstructed image. Finally, the metal implant regions in the initial image are reprojected using a fan-beam projection algorithm to obtain approximate missing projections in the raw projection data (the black areas in FIG. 9( d )). These missing projections are next replaced by synthetic data from the next step.
Step 2: Replacing Scheme
[0050] For the following discussion we focus our attention on the helical CT single-slice scanner. The results can be extended to multi-slice and cone-beam scanners.
[0051] In helical scanning the patient table is transported continuously as the tube and 1D detector array rotate around the patient. The geometry of this scanning is shown in FIG. 10 . We consider an equiangular fan-beam geometry in which the detectors lie on an arc of a circle. Let the x-rays project into the xy-plane and the direction normal to this scan plane be z. The view and detector angles are denoted β in the range (0,2π) and y in the range (−γ m , γ m ).
[0052] The idea behind the replacing scheme is due to the fact that the two projections along the same path but in the opposite sides would be the same in the absence of table motion. So, in the presence of table motion which is a real case for a CT exam, the opposite side projections are still very good approximations for the corresponding projections. The question is how we can compute the opposite side of a projection since in a fan-beam scanner the opposite sides are not exactly in 180 degrees apart. FIG. 11 shows the corresponding paths for computing the opposite angular positions. As we can see the opposite side of an x-ray beam (or a projection) depends on the position (or y) of this beam in the x-ray source. More clearly, a description of projections and their opposite sides is given with reference to FIG. 12 showing the γ vs β space (or sinogram). The letters A, B and C show the projections at β=0. The letters A′, B′ and C′ are showing the opposite side of the projections A, B and C respectively. Note that only for B which is a projection at γ=0, the opposite side lies on β=π. For other projections the opposite sides lie on a line where β=π−2γ. Thus, for each projection in the sinogram, its opposite side can be computed. However, because projections are given in discrete domain upon a finite uniform grid and not in a continuous form, interpolation is required in order to estimate the value of the required opposite side projections. We perform a bicubic interpolation using four nearest projections to compute the value of opposite sides.
[0053] The replacing scheme is followed by firstly projecting the metal components of the CT image, as identified in the step 1, onto the original sinogram, to detect missing projections and then by replacing each missing projection by its opposite side. When the replacement scheme is started for the first missing projections in the sinogram, they are replaced by their non-affected-by-metallic-object projections in opposite side. But, as we progress the replacing scheme for other missing projections, their opposite side projections may be the missing projections already replaced by their own opposite sides. Consequently, there is a risk that the errors in each step of replacing scheme are accumulated so that the synthesize date for replacing scheme become totally unreliable. Actually, this is the reason why we are limited to use the replacing scheme for the metallic objects with small size which appear in a limited number of CT slices. In order to make the replacing scheme more reliable, we propose to start it simultaneously from each side of missing projections area. FIG. 13 illustrates this strategy. We start replacing the missing projections (the black area) from AB to EF by their opposite side projections from left side of sinogram and simultaneously from CD to EF by their opposite side projections from right side of sinogram. It results a less accumulation of errors and therefore improves the performance of the replacing scheme. Finally a smoothing filter (size of 5×5 pixels) is applied in the boundary of replacement regions to remove any possible discontinuities in adjacent projections and resulted additional artifacts.
Step 3: Reconstruction of CT Images
[0054] The whole modified raw projection data arising from Step 2 is transferred back to reconstruction operator of CT scanner to regenerate slice images. So, all detail information on scanner geometry and file format is preserved and no changes in routine practices are needed.
Results
Phantom Data
[0055] To quantitatively evaluate the performance of this algorithm for reducing metal artifacts, a phantom was used. This phantom is routinely employed for this CT scanner calibration. The phantom consists of several cylindrical inserts representing human organ densities (such as lung, muscle, liver, bone, etc.) embedded in a block of masonite in the form of human abdomen. We inserted two steel rods on each side of the phantom to represent the hip prostheses. The size of the rods was chosen to produce the same quantity of artifacts as in a real case. The phantom was scanned by a Siemens Somatom in helical mode with a pitch of 1.5 and 3-mm slice thickness with 130 kVp and 168 mA (which are the typical parameters for a pelvis scan) for two cases: without rods (case A) and with rods (case B). The raw projection data consisted of 1344 detectors and 1000 gantry positions in each tube rotation. FIGS. 5( a ) and 5 ( b ) show the original reconstructed images (512×512 pixels) for Case A and case B and FIG. 5( c ) illustrates a significant improvement when the metal artifact reduction algorithm is applied on projection raw data of case B. We name this image case C. Two validations were used to evaluate the quality of images in cases B and C related to original case A.
[0000] Distortion validation: We applied a Canny edge detector to automatically detect the boundary of different objects in the phantom. We used the same parameters for the detector in three cases. FIGS. 5( d ), 5 ( e ), and 5 ( f ) show the results for cases A, B, and C respectively. Many objects are missing in case B because artifacts are strong in their area. Especially, the detector cannot find the round objects located in the middle of the phantom and only the line segments representing the artifacts in the image are detectable. Meanwhile most round objects especially the three objects in the middle of the phantom can be successfully distinguished in case C. It proves that the algorithm not only improves the image quality but also it does not introduce any major deformation of the shape of the objects. When we try manually to find the objects in the image, all objects can be detected in case C.
[0056] CT number validation: We computed the statistical parameters of CT numbers, i.e. mean and standard deviation (std), for three regions representing the three objects in the middle of the phantom (see FIGS. 5( g ), 5 ( h ), and 5 ( i )). Table I resumes the results for cases A, B, and C. Comparing case B to the original case (A), we can see that the noise (std) is very high in case B and the mean values are negative and quite different for the three regions. On the other hand, in case C, the values are close to the original case and consequently represent the objects almost with the same material density as those in case A.
[0000]
TABLE I
STATISTICAL PARAMETER COMPARISON
Region 1
Region 2
Region 3
mean
std
mean
std
mean
Std
Case A
47.4
19.8
57.7
21.3
238.7
20.9
Case B
−189.3
360.8
−272.2
432.5
−94.2
325.6
Case C
37.0
24.3
42.1
30.3
215.6
26.3
[0057] From these validations, we conclude that the proposed approach improves the overall image quality and more importantly preserves the form and, in a large proportion, the representative CT number of objects in the image.
Patient Data
[0058] Many patients with hip prostheses are scanned each year at this institution. Recently, four patients with two hip prostheses were scanned and treated for prostate cancer in this institute. Here, we show the results for one of these patients. The same parameters as the above phantom experiment are used for the scanner. FIG. 6( a ) shows the topogram for this patient. FIGS. 6( b ) and 6 ( c ) are representative slices of the patient and its modified image resulting from this artifact reduction algorithm. As it can be seen, the artifacts of two hip prostheses ( FIG. 6( b )) are almost completely eliminated in FIG. 6( c ). The remaining minor streaking artifacts are due to metal markers which are not removed by the algorithm. FIGS. 7( a ) and 7 ( b ) show DRR for original and modified cases using the complete image sequence.
[0059] Note that because of the interpolation step, information from the structures of metal implants is lost. We simply detect and contour the metal implants in the original images and then merge this information into the modified reconstructed images. Finally, we override the density inside the metal implant contours with a value closer to the real implant. FIG. 7( c ) shows a DRR for this last modification.
[0060] Following recommendations from the report of task group 63 of the AAPM Radiation Therapy Committee, we basically plan beam arrangements that avoid prostheses to shadow the target. This kind of planning on patients with two hip prostheses requires precise delineation of the target and sensitive structures. The improvement in image quality provided by the metal artifact reduction algorithm enables this approach without compromising target dosage and normal tissue complication probabilities. Without image quality enhancement, physician would have drawn bigger margins to be sure to include the target and at the same time, would have prescribed lower dose in order to keep the same level of normal tissue toxicity.
[0061] For a real patient with metallic teeth fillings, the topogram and a portion of the sinogram containing the affected projections by metallic objects are shown in FIGS. 14 and 15 respectively. FIG. 16 shows the sequence of CT images reconstructed by a Siemens Somatom scanner using this original sinogram. As we can see, strong streak artifacts are present in these CT slices. The modified sinogram resulted by applying the presented approach is demonstrated in FIG. 17 . As seen, the trace of missing projections is completely removed and replaced by appropriate values. By transferring back the modified sinogram to the reconstruction operator of the scanner, CT images of FIG. 18 were obtained. Note that in FIGS. 16 and 18 , the contrast (L=2321 and W=46) for all images is the same. All images in FIG. 18 compared with those in FIG. 16 show a superior image qualify. The images show almost no trace of artifacts, especially for teeth structures in which the details are very well revealed.
[0062] In order to evaluate the performance of the presented approach, we applied an interpolation-based algorithm on the same patient exam. FIG. 19 shows the results. The original CT image is shown in FIG. 19( a ). The image reconstructed using the projection-interpolation algorithm is shown in FIG. 19( b ). As we can see, because the image containing multiple adjacent metallic objects, interpolation was performed over a larger region of projection data. So, the interpolation becomes less reliable and the artefacts are not completely removed. In addition, the algorithm distorts the structure of the teeth directly adjacent to the metallic objects. As seen in FIG. 19( c ), the presented approach almost completely eliminates the metal artefacts. Especially in regions directly adjacent to the metallic objects there is an increase in image quality.
[0063] Our proposed replacement scheme is independent from the type of metallic object. However, in metal detection step, the threshold depends favorably on Z so that for high Z materials, the threshold will be augmented and vice versa. Consequently, the detection step is automatically adjusted for a different Z objects. The approach is entirely automatic and can be used easily by relatively little user interaction. Additionally, since the Head and Neck tumour treatment planning is often performed while the patient is waiting, the approach does not increase the time to the planning process and it can be clinically applicable. | A method for reducing artifacts in an original computed tomography (CT) image of a subject, the original (CT) image being produced from original sinogram data. The method comprises detecting an artifact creating object in the original CT image; re-projecting the artifact creating object in the original sinogram data to produce modified sinogram data in which missing projection data is absent; interpolating replacement data for the missing projection data; replacing the missing projection data in the original sinogram data with the interpolated replacement data to produce final sinogram data; and reconstructing a final CT image using the final sinogram data to thereby obtain an artifact-reduced CT image. | 0 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates, in general, to a method and apparatus for continuously carrying out a gas phase reaction, and in particular, to an improved method and wave reactor apparatus for chemically synthesizing gases by subjecting them to compression and expansion waves.
2. Description of the Prior Art
The wave reactor is a relatively simple device in which gases are made to react with one another in a continuous manner by application of compression and expansion wave techniques. The unique characteristic of compression and expansion wave technology is that the gas which is subjected to the waves may be heated to extremely high temperatures very rapidly, and then cooled at extremely rapid rates with very precise control over reaction parameters. For industrial utilization, an ideal high-temperature chemical reactor must raise the reactant gas to the required reaction temperatures and cool the high temperature products fast enough so that there will be a minimum of product lost during the cooling process while at the same time minimizing circulating power losses and initial capital investment.
The background of the present invention may best be described with reference to one particular chemical reaction which may be carried out in accordance with the instant invention, namely, the fixation of nitrogen, hereafter simply termed NO, from air. Once nitrogen has been fixed as NO, the succeeding steps to the creation of nitric acid are relatively straightforward. Nitric acid is a well-established feedstock in fertilizer production. For example, the treatment of readily available limestone with nitric acid leads to the formation of "Norwegian Saltpeter", or, the treatment of ammonia leads to the creation of ammonium nitrate often considered one of the most useful forms of high concentration fertilizer. During World War I the Haber method of direct fixation of nitrogen was developed whereby nitrogen was combined with hydrogen under extreme pressures to form ammonia. With the birth of the great petroleum boom in the United States in the early post World War I years, the use of natural gas as a feedstock for the chemical industry was quickly exploited due to the ease with which natural gas could be used. In particular, methane was a source of cheap hydrogen, one of the chief requirements for the production of Haber ammonia.
By the end of World War II, the agriculture-chemical fertilizer industrial complex based on the Haber process had grown to the point where the United States was able to create a substantial oversupply of food. The combination of the progressively dropping price of fertilizer and the progressively sophisticated development of hybrid grains, particularly corn, appeared able to continue without limit. Nevertheless the alternative approach of fixing nitrogen from air, was pursued by a few visionaries, most notably Farrington Daniels. Daniels' concept involved heating air in a regenerative heat exchanger followed by a rapid quench to create high volumes of low concentration NO. Daniels' approach, however, was doomed to failure due to the technical limitations of the high temperature pebble-bed heater which he used and to the nearly violent expansion of the natural gas industry resulting in the creation of a market for natural gas in which this valuable and limited resource was literally given away at prices far below its equivalent energy value. It became clear that even for the production of nitric acid, Harber ammonia would compete economically with nitric acid produced from the fixation of air by the Farrington Daniels' approach and support for the Farrington Daniels' approach was withdrawn.
Between 1950 and 1960 the science and technology of high-energy gasdynamics was a fallout of the scientific developments created during World War II. Among these was the shock tube which presented to the scientists a convenient tool for the study of high temperature gas properties. A group at Cornell Laboratory which was involved in the study of nonsteady gasdynamics exhibited in shock tube type devices, began a serious set of investigations into the structure and nature of air at high temperatures. It was quickly realized by this group that at high temperatures, strong concentration of NO could be achieved directly by shock heating of gases. The concentrations, depending on the temperature, would easily exceed that of the heater reactor of Farrington Daniels and under optimal conditions could approach 5%. This possibility led to the development by this group of the device called the "chemical shock tube" which was specifically designed to create high temperature pulses in order to study the kinetics of the formation of NO as well as the necessity and appropriate mechanisms for retaining the equilibrium concentrations. Apparatus was designed and constructed for carrying out the gas phase reactions on a continuous basis, the apparatus designed being based in part upon a new class of machinery called the "comprex" which had been developed by Seippel as a device for improving the efficiency of gas turbine machinery. See Seippel U.S. Pat. No. 2,399,394. Abraham Hertzberg, one of the coinventors of the present invention, was personally involved in the work at Cornell and U.S. Pat. Nos. 2,832,666, 2,902,337, 2,930,196, 3,326,452 and 3,367,563, as well as Paper No. 66-GT-117 of the "Journal of Engineering for Power," substantially describe the nature and results of that work.
To summarize, the Cornell group conceived of a wave reactor apparatus which was designed to use compression forces generated therein to superheat a reactant gas, maintain the high temperature of the gas long enough to promote equilibrium formation and then suddenly cool the mixture by rapid expansion to preserve the desired equilibrium. By programing the wave processes, the apparatus was designed to recover as much of the desired reaction product as possible, consistent with the gasdynamics and working capability of machinery available at that time. In an NO formation reaction, the reacted air which had completed the high temperature portion of its cycle in the wave reactor left the reactor enriched with NO and was then further cooled by a regenerative heat exchanger. The driver cycle which carried out the function of a piston to compress the reactant gas was basically a system similar to that shown at the left-hand side of the broken lines 10 in FIG. 1 of this application as will be discussed in more detail hereinafter. In that system all make-up work was supplied by shaft power purchased off the line in the most convenient manner. This cycle proved to suffer from a number of dificiencies which led to excessive energy and capital requirements. In particular, the compressor and turbine components of the driver resulted in large circulating power losses and excessive capital investment. Nevertheless, this was a significant step beyond the Farrington Daniels' approach.
In a related project at Cornell, a large scale superheater facility was constructed which included a five foot diameter rotor drum with 288 individual shock tubes arranged around the circumference. This apparatus processed about five pounds of air per second at temperatures in excess of 4500° K and is additionally discussed in the following articles:
W. e. smith and R. C. Weatherston, "Studies of a Prototype Wave Superheater," CAL Report No. HF-1056-A-1, AFOSR TR 58-158 AD 207244, December, 1958;
A. h. flax, A. Hertzberg, and W. E. Smith, "A New Method for Providing Continuous High-Temperature Airflow for Hypersonic Research," CAL Report No. 79, AFOSR TN 56-236, May, 1956;
R. c. weatherston, W. E. Smith, A. L. Russo, and P. V. Marrone, "Gasdynamics of a Wave Superheater Facility for Hypersonic Research and Development," CAL Report No. AD-118-A-1, AFOSR TN 59-107, February, 1959; and
J. carpenter, "Engineering Design of a Wave Superheater Facility for Hypersonic Research and Development," CAL Report No. AD-1118-A-2, AFOSR TN 59-108. February, 1959.
Also of interest to the present invention are Hansel U.S. Pat. Nos. 3,272,598 and 3,254,960 and Hansel et al. U.S. Pat. No. 3,307,917 which disclose the heating and rapid cooling of gases other than air in a continuous flow shock tube process and the use of alternate drivers such as hydrogen to reduce the circulating power requirement.
In accordance with the instant invention, substantial process, method and apparatus improvements have been made in the above described wave reactor approach whereby both the circulating power and capital cost structure are radically improved.
BRIEF SUMMARY OF THE INVENTION
While the above described combustion driven wave reactor system was a significant step leading to the development of a chemical process whereby a reactant gas could be subject to high reaction temperature and rapid cooling, this system was too complicated and inefficient to be adapted to large scale industrial uses. As applied to nitrogen fixation in particular, the complexities and inefficiencies have prevented this technique, prior to the instant invention, from being competitive with other known nitrate formation techniques. Examination has indicated that losses associated with the driver gas in a wave reactor apparatus were particularly serious. For example pumping losses alone in bringing a driver gas such as air up to the pressure required in the fixation of nitrogen, cycling it through the reactor and then reexpanding it through a turbine, proved to involve energy requirements which virtually eliminated this system from consideration on the basis of energy demands alone. In accordance with the instant invention, it has been found that in a wave reactor system the driven gas may be removed at higher total pressures than it had upon entering the reactor. In particular, the driver gas may be removed and recirculated in stages of differing total pressures with the exit pressure of the gas being greater in each stage than the entrance pressure of the same stage.
In one disclosed embodiment, the driver system no longer involves the necessity of a pump, a compressor, or an expander system and acts only as an effective fly wheel to store the energy required for the driver gas. In the present invention the role of the driver gas and the reactant gas may in one aspect be said to be interchanged since the driving energy for the system now comes from the reactant gas while in prior art wave reactor systems the driver gas usually supplied excess energy to the reactant system. Stated somewhat differently, all energy required to drive the disclosed system comes from a pressure drop in the reactant gas flowing through the system and the driver gas system may be considered simply as an idling fly wheel which first extracts and then returns its energy to the system. All friction losses are made up by the pressure drop of the reactant gas flowing through the reactor.
A significant characteristic of the present invention, when applied to the production of NO, lies in the dryness of the end product. The dry end product realized is significantly different from the NO produced by the burning of ammonia, and permits the plant designer to choose from a wider variety of product separation processes.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a flow chart of a prior art process for continuously carrying out a gas phase reaction in a wave reactor which requires a high temperature to promote the reaction and rapid cooling to preserve the reaction product, including broken lines indicating that portion of the apparatus not needed for performance of the method of the present invention.
FIG. 2 is a diagram of the chemical reactor portion of the flow diagram of FIG. 1 illustrating the recirculation of the driver gas in accordance with the present invention.
FIG. 3 is a perspective view of a chemical reactor constructed in accordance with the instant invention with a portion of the rotor being broken away to illustrate the tubes therein, and with hatched lines being provided to portray the movement of the driver and reactant gases within the tubes during processing.
FIG. 4 is a partially schematic, partially graphic diagram illustrating one embodiment of a staged recirculation system for the driver gas including a pressure diagram illustrating the relationship between exit and entrance pressure in each stage and between stages.
FIG. 5 is a diagram illustrating the interaction of the various waves developed in the reactor of FIG. 3 during a typical gas phase reaction, the abscissa of this diagram representing the axial distance along the length of the reactor tubes, and the ordinate representing a portion of the developed circumference of the chemical reactor and also time.
FIG. 6 is a diagram illustrating the reactant gas temperature history plotted along the left-hand side of the diagram of FIG. 5 during a typical gas phase reaction carried out in accordance with the present invention.
FIG. 7 is a diagram illustrating the interaction of the various waves developed during a typical gas phase reaction carried out in accordance with the instant invention in a reactor of the double ended type wherein compression of the reactant is carried out in the central portion of the reactor tubes in response to the simultaneous introduction of opposing pairs of compression waves at opposite ends of the tubes.
DETAILED DESCRIPTION OF THE INVENTION
In general, a gas phase reaction is carried out in accordance with the present invention by introducing the reactant gas into the upstream end of a chamber or reactor tube of a chemical reactor apparatus to be described hereafter, the introducing at the appropriate time a pulse of pressurized driver gas into the downstream end of the chamber or reactor tube whereby a compression wave and also a fan pattern of expansion waves are generated which propagate upstream through the reactant gas. Passage of the compression wave through the reactant gas toward the upstream end of the chamber or reactor tube raises the reactant gas to reaction temperature and the subsequent passage of the expansion waves through the reactant gas cools the same rapidly so as to preserve the reaction product. The compression wave and expansion waves are successively reflected near the upstream end of the chamber or reactor tube whereby the driver gas is first expelled from the downstream end of the chamber or reactor tube and then the reaction product is thereafter expelled or scavenged from the downstream end of the reactor tube means. In accordance with the instant method and apparatus, as will be described more completely hereafter, the total inlet pressure of the driver gas is less than the total outlet pressure of the driver gas and thus in one embodiment, the driver gas may be recirculated from tube to tube of the chemical reactor without the input of pump work. In another alternative embodiment, pump work may be added to the exhausted driver gas, however the pump work is generated from the reactant gas stream.
It will be recognized that FIG. 1 is substantially the same as FIG. 1 of U.S. Pat No. 2,832,666, additionally however, broken lines 10 have been added to the drawing to illustrate the equipment savings provided by the instant invention as compared with typical prior art equipment. U.S. Pat. No. 2,832,666 discloses the basic theory and operation of a wave reactor apparatus and thus applicants hereby incorporate the disclosure of this patent by reference in this application. For like reason applicants also incorporate herein by reference the disclosure of U.S. Pat. No. 2,902,337 which discloses the basic theory and operation of what may be termed a "double ended" wave reactor apparatus where compression of the reactant gas is carried out centrally in the reactor tubes rather than adjacent a sealed end of a reactor tube. While the present invention is described hereafter primarily with respect to a wave reactor generally of the type disclosed in the 2,832,666 patent, it will be understood that the present invention may also be carried out through use of so-called double ended type reactors.
In FIG. 1, reactant gas, the composition of which may vary depending upon the chemical reaction intended to be carried out within the chemical reactor 12, enters blower 14 through reactant gas inlet line 16. The blower 14 may be of any suitable type and is shown as being driven by a turbine 18, which is in turn partially driven by a prime mover 20. The turbine 18 and the prime mover 20 may be of any conventional type suitable for the described purpose.
The reactant gas leaves the blower 14 through line 22 and is conducted thereby to a heat exchanger 24 which also may be of any suitable conventional type. In passing through the heat exchanger, the reactant gas picks up heat and is then conveyed through line 26 to a reactant gas inlet area of the chemical reactor 12. The reactant gas inlet area is arranged at the end of the chemical reactor 12 opposite the end at which the driver gas inlet and outlet areas and the reaction product outlet areas are located.
It will be understood that where the reactant gas to be processed is air, it may be desired to place additional apparatus in the reactant gas flow line prior to its entering chemical reactor 12 to remove water vapor from the air. While the term "dry" is used in the present application to describe the fact that the process carried out in accordance with the present invention adds no additional moisture to that found in ambient air, with proper treatment the reactant air can be made totally or near totally dry, thus producing totally or near totally dry reactant products including NO.
After the preheated reactant gas is processed within the chemical reactor 12 the processed reactant gas is discharged from the chemical reactor into the reactant product outlet line 28 which conducts the heated reactant product to the heat exchanger 24 through which it flows and in so doing gives up some of its heat to the reactant gas passing from the blower 14 to the reactor 12. The cooled reactant product gas leaves the heat exchanger through line 30 and is conducted to turbine 18 where is serves to partially drive the turbine and then exits through discharge line 32. The reactant product gas discharged through line 32 is reclaimed in any suitable manner and by any suitable apparatus for making the most effective use of the reactant products resulting from the chemical reaction carried out within the chemical reactor 12.
In prior art apparatus, the driver gas which enters reactor 12 through line 34 and exits through discharge line 36, itself required substantial compression and heating prior to its use to compress the reactant gas within the reactor. FIG. 1 from U.S. Pat. No. 2,832,666 contemplates the products of combustion between air and hydrocarbon fuel as the driver gas. Air enters a compressor 38 through inlet line 40, the compressor being suitably driven by a turbine 42 which is in turn partially driven by a prime mover 44 the compressed air discharged from the compressor is carried by line 46 to a heat exchanger 48 and the compressed and heated air leaving the heat exchanger is conducted by line 50 to combustion chamber 52. In the combustion chamber the heated and compressed air and fuel mixture is combusted in a suitable manner to provide a hot, compressed driver gas which is conducted by line 34 to the driver gas inlet area of chemical reactor 12. After the driver gas is discharged from the chemical reactor it is carried by line 36 back to the heat exchanger, and thence by line 54 to the turbine, back to the heat exchanger through line 56, and is finally discharged to the atmosphere through line 58.
In both the apparatus of the instant invention and that of prior art wave reactors a cooling gas may be passed through the reactor to lower the temperature levels of the reactor tubes although it will be understood that in some instances the reactor may be advantageously operated without extenal cooling. If cooling is desired, the cooling gas may be air drawn from the atmosphere into a blower 60 through intake line 62 (FIG. 1). Blower 60 may be driven by any suitable prime mover 64. Air discharged by the blower is conducted through line 66 to the cooling gas inlet area of the chemical reactor and is then exhausted to the atmosphere through exhaust line 68 after passing through the reactor tubes.
Referring now to FIG. 2, a chemical reactor 70 constructed and operated according to the instant invention is disclosed in diagram form to illustrate the continuous circulation of the driver gas through the reactor without the addition of heat or pump work. As will be discussed more completely hereafter with reference to FIGS. 3 and 4, in the illustrated embodiment the driver gas stream includes a plurality of conduit members 72 which conduct portions of the exhaust driver gas from tubes of the chemical reactor which have moved adjacent the exhaust nozzle opening associated with the conduit member to other reactor tubes of the rotating reactor disc which have moved adjacent an inlet nozzle at the distal end of the conduit. The embodiment illustrated employs three conduits to recirculate the driver gas in three discrete stages, but it will be understood that a greater or lesser number of recirculation stages may be employed to produce maximum efficiency depending on the nature of the reaction products and other variables. It will be further understood that the reactor 70 of FIG. 2 may be substituted for the reactor 12 of the portion of FIG. 1 to the right of broken lines 10 to produce a flow diagram representing the method and apparatus of the present invention. The instant invention thus provides not only capital cost savings through the elimination of the driver gas prime mover, turbine, compressor, heat exchanger and combustion chamber shown to the left of broken lines 10 in FIG. 1, but of equal or greater importance, also provides a method and apparatus of increased efficiency in that the losses which are necessarily associated with the eliminated equipment are avoided.
FIG. 3 illustrates a rotary wave reactor 70 constructed in accordance with the instant invention including a cylindrical member 74 rotatable on a shaft 76 and two stationary wall members 78 and 80 positioned adjacent the opposite ends of the rotatable cylindrical member 74 and adapted to intermittently seal the open ends of tubes 84 in a manner described hereafter. The rotatable cylinder 74 has a plurality of open ended tubes 84 oriented parallel to shaft 76 and positioned around the periphery of the cylinder. Tubes 84 are shown as being circular in cross-section but it will be understood that tubes of other shaped cross-section may also be used. The tubes may be formed by any conventional means such as by drilling or casting.
While it will be understood that this invention is not intended to be limited to the carrying out of any particular chemical reaction, for illustrative purposes the invention will be described hereafter with respect to the earlier discussed process for the fixation of nitrogen from air employing air as a driver gas. It is understood driver gases other than air such as nitrogen, hydrogen or steam, may also be used advantageously in the present invention for the fixation of nitrogen from air, however the use or steam as a driver may require the further use of a buffer gas such as nitrogen between the driver and the reactant gas to prevent contamination of reactant gas by water vapor or other undesirables.
Reactant (air) inlet manifold 86 is shown positioned adjacent stationary wall member 78. Reactant air inlet areas 88, 90, 92, 94, 96 and 98 interconnected with manifold 86, are shown spaced around the periphery of stationary wall member 78. The reactant air inlet areas may include inlet nozzles adapted to lead reactant air from the inlet manifold through openings such as 100 in wall member 78 through which reactant air enters the upstream end of tubes 84 as they are rotated thereby. It will be understood that a conventional reactant air heating and pressurizing system such as that discussed earlier with respect to FIG. 1 may be employed to provide air to inlet manifold 86.
Driver gas recirculation system 102 is disclosed adjacent stationary wall member 80 at the opposite downstream end of the reactor tubes. Recirculation system 102 includes the earlier discussed conduits 72 communicating between exhaust nozzles 104 and inlet nozzles 106. Conduits 72 carry the driver gas from exhaust nozzles 104 to inlet nozzles 106 where the gas passes through an opening in stationary wall 80 into the open ends of tubes 84 as they pass rotatably thereby.
Reaction product (depleted air + nitric oxide) outlet manifold 112 is also positioned adjacent stationary wall 80 and includes conduits 114 adapted to lead the gaseous reaction product from an opening 116 in stationary wall member 80 to outlet manifold 112. It will be understood that the reaction product may be withdrawn from manifold 112 and processed in any desired manner and that the heat may, if desired, be withdrawn therefrom in a heat exchanger or turbine as shown in FIG. 1 (at 24).
Reactor 70 of FIG. 3 also includes a cooling stage for tubes 84 comprising conduit 118 through which cooling air is led to an opening 113 in stationary member 78 through which the cooling air enters the tubes 84 and is exhausted through a like opening (not shown) in wall 80 at the opposite ends of the tubes and thence to the atmosphere through conduit 120. As stated heretofore, the cooling stage may be omitted from operation of the unit if desired.
In a typical air compression process in accordance with this invention, a preheated reactant gas is introduced into the "left" or "upstream" end of tubes 84 of FIG. 3. As the wave reactor rotor rotates, a heated driver gas is introduced into the downstream end of the same tubes 84 to compress and heat the reactant gas. The driver gas is then exhausted from the downstream end of the tube 84 at a pressure higher than its entrance pressure into the tubes 84 while the reactant gas is expanded and cooled. The exhausted driver gas is then circulated into the downstream end of others of the tubes 84 in a manner such that the driver gas enters these second tubes at the same pressure as it had upon entering the first tubes 84. Finally, the reactant products are exhausted from the downstream ends of the first tubes 84.
As illustrated, the reactor apparatus 70 is designed to carry out six air compression processes within each of the reactor tubes during one revolution of rotor 74. Considering only a single compression process, as each of the tubes 84 pass the reactant gas inlet 88 the reactant gas to be subjected to the heating and cooling cycle passes into the tubes 84 through the opening 100. As member 74 rotates, the opposite downstream end of each tube 84 passes inlet nozzles 106 through which high pressure driver gas is introduced into the tube. As disclosed with respect to the selected embodiment of the invention discussed herein, the driver gas enters each of tubes 84 in three stages, although it will be understood that the driver may be introduced in a greater or lesser number of stages if desired. The impact of the high pressure driver gas upon the reactant gas generates compression waves which travel from right to left in FIG. 3 through the column of reactant gas in tube 84 toward stationary wall member 78 and are reflected back toward the downstream end of the tube. In the meantime, the downstream end of the tube has rotated beyond the driver gas inlet nozzles whereby the flow of driver gas into the tube is cut off. Cutting off the driver gas flow generates an expansion wave which follows the compression waves through the tube and is also reflected back toward the downstream end of the tube. The combined effect of the expansion waves and the reflected compression wave moves the driver gas back out ot the tube which has now rotated adjacent the driver gas exhasut nozzles 106. Removal of the driver gas allows the reactant product gas to expand to the original volume of the reactant in the tube. Further rotation of the tube brings the downstream end of the tube adjacent outlet 114 which allows the reactant product gas to flow out of the tube. As illustrated by arrows 122, the driver gas is exhausted from tubes 84, enters conduits 72 through nozzles in exhaust areas 104 and is recirculated through conduits 72 directly back to inlet nozzles in inlet areas 106 whence it enters other tubes 84.
While prior art wave superheaters employed a five foot diameter rotor with a top speed of 700 ft/sec, 288 tubes about 66 inches long, and adapted to operate at a pressure of up to 136 atmospheres and reactant air temperatures of up to 8000° R, the requirements of the advanced wave reactor of this invention are much more modest. The apparatus of the instant invention is typically designed for operation with tube lengths of between 10 and 50 cm and maximum gas temperatures of approximately 3300° K. A rotor speed of 700 ft/sec is assumed with a tube length to diameter ratio of approximately 25 which is consistent with present shock tube experience.
A typical wave reactor point design suitable for 100 ton per day HNO 3 production and assuming weak shock compression with γ = 1.3 is as follows:
______________________________________t o max° K 3,300P o maxatm. 200Temperature Ratio 3Length, cm. 10Yield, % NO 4.9Mass Flow, lbs/sec. 22.5T o in° K 1,100Inlet Mach No. 0.4P.sub.in.sup.atm. 2.0Duty cycle 1/3Tube Diameter, cm. 0.4No. of Tubes/Rotor 14,200Rotor Diameter, cm. 120No. of rows 15Rotor Speed rpm. 3,300______________________________________
Recirculation of the driver gas in accordance with this invention may be more clearly understood by reference to FIG. 4. In this figure, the driver gas inlet and exhaust areas associated with a single compression cycle in a tube are represented by rectangles labeled I, I 1 and I 11 (Inlet areas 106) and X, X 1 and X 11 (Exhaust areas 104). FIG. 4 additionally includes in its upper portion a pressure diagram illustrating the reative pressures at the respective inlet and exhaust areas of the reactor tube. As will be seen, the driver gas which enters a reactor tube at I has been conducted there through a conduit 72 from exhaust nozzles located in driver gas exhaust area X. Reference to the pressure diagram illustrates that the pressure of the driver gas is higher at X than at entrance area I, i.e. that the driver gas is removed from the reactor tubes at X at a pressure higher than its entrance pressure into the reactor tubes at area I. This pressure difference, which is shown as the cross-hatched area 123 on the pressure diagram, is provided by energy drawn from the compression and expansion of the reactant gas, and should be of such a size that all pressure losses occurring in the recirculation of the driver are balanced so that the pressure at driver gas inlet area I remains constant without the additoin of work to the recirculating driver outside of the chemical reactor.
FIG. 4 additionally illustrates that the recirculation of the driver gas between exhaust areas X 1 and X 11 and driver gas inlet areas I 1 and I 11 respectively is carried out in substantially the same manner as discussed heretofore with respect to exhaust area X and inlet area I. It will be noted, however, that in the three stage recirculation system which has been chosen for illustration, the total pressures of the stages vary with rspect to each other with pressures progressively increasing from stage I-X through stage I 11 -X 11 . It is presently contemplated that it may be desirable to vary the size of the driver gas exhaust areas 104 and thus driver gas exhaust area X is shown to be somewhat larger than area X 1 which is in turn somewhat larger than X 11 .
Again considering an air reactant-air driver nitrogen fixation process as carried out in a chemical reactor of the type shown in FIG. 3, designed in accordance with the point design set forth above, the interrelationship of the variables within the reactant cycle may be examined with respect to the wave diagam shown at FIG. 5 utilizing ideal gas characteristics. The wave diagram of FIG. 5 shows typical characteristics and operating parameters for such a cycle. High pressure reactant air is taken into the reactor from a conventional preheater in a steady flow region shown in the lower left of FIG. 5 at 124 (i.e. 88 in FIG. 3). The inlet Mach number is 0.68 to minimize losses while the inlet pressure of the gas entering the tubes is set at approximately 3.5 atm.
To initiate the cycle, the inlet air may be brought to rest by a weak hammershock indicated by wave line 126 which raises the pressure in the tube and brings the reactant gas completely to rest. The pressurization of the reactant gas is then carried out intil the gas is brought to its final reaction condition. Dashed line 128 indicates the interface between the reactant and driver gases as the process is carried out.
To maximize efficiency, an isentropic compression wave was selected as idea. In reality the equipment may be tuned to closely approximate the ideal. The initial driver inlet velocity (M = 0.63) is such that the leading edge of the compression wave is essentially an acoustic wave. Driver gas enters the system at 130 (i.e. 106 in FIG. 3) and the pressure on the driver inlet side of the tube is raised in time (or in angular location, as the reactor is rotated) to form the family of waves which are reflected and focus at the termination 132 of the driver gas inlet area.
An examination of the pressure history of the gas coming into the tube (84 in FIG. 3) reveals that if the gas is taken to be air and the impedance across the interface 128 is kept constant, i.e. the velocities of sound are maintained equally, the pressure rise from the pressure after hammershock to the final pressure of the reaction gas proceeds in a step-wise manner. In the chemical reactor this pressure development is replicated by a series of focused weak shock waves 134 with little loss of efficiency, i.e. an insignificant entropy rise.
At the end of the reaction cycle, the reactant gas has been compressed and heated to the selected conditions under which the reaction takes place at 136. As illustrated in FIG. 5, considerable reaction dwell time is allowed, but this can be controlled by choosing the point of origin of the cooling expansion waves. After allowing the appropriate time for the reaction to occur, the next phase of the cycle involves a sudden quenching of the reaction and the cooling of the gas. In the illustrated case the expansion wave is initiated by the reactor tube 84 rotating adjacent the driver exhaust areas thus allowing the driver gas to begin flowing out as indicated at 138. This step up an expansion wave 140 which is nearly the reflected image of the previously used compression wave system. Here the wave must, be the nature of the process, also be isentropic.
The wave system then crosses the interface between the reactant product and the driver at 142 and begins to accelerate the reactant product back toward the driver exhaust end of the tube as the driver gas flows out of the tube. As chosen, the driver gas exhaust pressure is slightly above the driver gas inlet pressure thus assuring proper recirculation of the driver without the need for auxiliary pumping. In the system discussed with reference to FIG. 4, the driver gas is self-scavenging with no external assistance, however in some cases some external scavenging assistance may be desirable.
It should be pointed out that in accordance with this invention, and as an alternative to maintaining the driver exhaust pressure at a level higher than the driver inlet pressure, the back pressure of the driver gas may be increased by pump work obtained from the reactant gas stream. In this manner, the driver gas still acts only as a fly wheel driver piston with all energy losses being compensated from the reactant gas stream.
After the driver gas leaves the tube 84, the reactant product is scavenged at 144 (conduit 114 in FIG. 3) at a temperature slightly below the reactant intake temperature at 124 which is set by the maximum temperature allowable without destroying the NO produced. This temperature sets the limits on the process rather than heat exchanger technology. The scavenging process acts automatically to induce an expansion wave system at 146 which is desigend to bring in the fresh charge of reactant as indicated at 124'.
The temperature history of the reactant gas through the process discussed above with reference to FIG. 5 and as measured at the reactant inlet side of the reactor is shown in FIG. 6. In the described case, the reactant and driver were both nominally chosen to be air, but it is contemplated that a lower molecular weight driver may be used advantageously at a corresponding lower temperature.
Referring finally to FIG. 7, a wave diagram is disclosed showing an operating sequence for a double ended wave reactor operating in accordance with the method of the present invention wherein the driver gas is removed from the reactor at a total pressure higher than its entrance pressure. In a reactor of this type compression of the reactant gas is carried out in the central portion of the reactor tubes in response to the simultaneous introduction of opposing paris of compression waves at opposite ends of the tubes. In this manner, compression of the reactant adjacent an end of the reactor tube which must be sealed is avoided. U.S. Pat. No. 2,902,337 discloses one form of double ended reactor and FIG. 7 is provided merely to illustrate that the method of the present invention can be carried out in this manner with avoidance of sealing problems associated with tube end compression.
The invention may be embodied in other specific forms without departing from the spirit or central characteristics thereof. The present embodiments are therefore 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, and all changes which come within the meaning and range of equivalency of the claims are therefore to be included therein. | A method for continuously carrying out the chemical synthesis of a gas in a wave reactor apparatus of the type wherein reactant gases subjected to compression waves generated by a driver gas may be heated to extremely high temperatures very rapidly and then cooled at extremely rapid rates with very precise control over reaction parameters. The method includes the step of removing the exhaust driver gas from the tubes of the wave reactor at a pressure greater than that which it had upon entering the tubes of the wave reactor prior to compression of the reactant. The driver gas is recirculated without the addition of heat or pump work other than that originating with the reactant gas stream. Apparatus for performing the above method is disclosed including a multi-tube rotor of novel physical dimension and a conduit and manifold system for recirculating the driver gas between tubes of the wave reactor. Particularly disclosed is a conduit and manifold system for staged recirculation of the driver gas. | 1 |
This is a continuation of co-pending application Ser. No. 874,490 filed on Jun. 16, 1986 now abandoned.
BACKGROUND OF THE INVENTION
This invention relates to a denture-base made of a compound comprising thermoplastic resins having different properties, which is excellent in appearance, mechanical properties, repairability etc.
Denture-bases have been produced for many years from acrylic resins by compression molding method wherein their polymers and monomers are polymerized by heat. An advantage of the acrylic resin denture-bases is that they can be readily repaired by use of acrylic polymer powders and acrylic monomer liquid as repair materials.
The acrylic resin denture-bases thus produced by thermal polymerization are, however, weak in strength so that thin portions therof are often broken by occlusal forces. In addition, the said denture-bases might be poisonous so as to cause allergy due to effluence of residual monomers resulting from incompletion in thermal polymerization reaction.
Denture-bases made of thermoplastic resins such as polysulfone have also been proposed and practically used to eliminate the above drawbacks of acrylic resins, which are produced by injection or compression molding in gypsum molds.
The denture-bases of thermoplastic resins such as polysulfone are superior in strength to those made of acrylic resins, because the thermoplastic resins such as polysulfone are excellent in impact resistance compared with conventional acrylic resins. However, the said denture-bases are difficult to repair and cannot endure a long-term use because they tend to have stress-cracking in contact with instantaneous polymerizing resins composed of acrylic monomers, particularly methyl methacrylate which is most commonly used for repairing acrylic resin denture-bases.
The application to denture-bases of polyester or polycarbonate resins such as polycarbonates, polyester carbonates, aromatic polyester copolymers and their mixtures, is under investigation. These resins are superior in compatibility with methyl methacrylate and have few stress-cracking in contact with methyl methacrylate, compared with the polysulfone resins as mentioned above. These resins, however, tend to have stress-cracking in contact with isobutyl methacrylate or normalbutyl methacrylate which is a component of relining resins or repair materials.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a denture-base made of thermoplastic resins which is excellent in mechanical properties and compatibility with acrylic monomers.
This object is accomplished by a denture-base made of a thermoplastic resin compound comprising polysulfone resins (A) and a resin (B) selected from the group consisting of polycarbonates, polyester carbonates, aromatic polyester copolymers and their mixtures.
The inventive denture-base is excellent in adhesion to artificial dentures of acrylic resin. And it is possible to apply to the inventive denture-base various instantaneous polymerizing resins which have been used as repair resins or relining resins for acrylic resin denture-bases. This invention, therefore, contributes to make expanded the scope of the application of thermoplastic resin denture-bases with various advantages.
DETAILED DESCRIPTION OF THE INVENTION
The polysulfone resins used in this invention can be defined as polyarylene compounds having arylene units which are arranged orderly or not together with ether linkage and sulfone linkage. Examples of the said polysulfone resins are those having structures (1)-(16) as follows: ##STR1## Particularly preferred are the polysulfone resins having the structures (1), (2) and/or (6) since they are well-balanced in physical properties and processability. Polysulfone resin of the type having the structure (1) is commercially available from ICI as Victrex® polyethersulfone. Polysulfone resin of the type having the structure (6) is also commercially available from UCC as Udel® polysulfone. The polysulfone resins preferably have a reduced viscosity of not less than 0.3 and not more than 0.6 as measured at 25° C. in a dimethylformamide solution containing 1 gram of the polymer in 100 ml of the solution, because the polysulfone resins having such a reduced viscosity are superior in physical properties such as heat resistance, strength and stiffness, and shapability.
The polycarbonates used in this invention are 4,4-dioxydiarylalkane polycarbonates which can be derived from 4,4-dioxydiphenylalkanes such as bis(4-hydroxyphenyl)methane, bis(4-hydroxyphenyl)ethane, 2,2-bis(4-hydroxyphenyl)propane, bis(4-hydroxy-3,5-dichlorophenyl)methane, 2,2-bis(4-hydroxy-3,5-dimethylphenyl)propane, bis(4-hydroxyphenyl)phenylmethane and phosgene or diphenylcarbonates. These polycarbonates are produced by various known methods such as melt polymerization, interfacial polymerization, etc.
The polyester carbonates used in this invention are obtained from component A of aromatic dicarboxylic acids and/or their functional derivatives, component B of aromatic dihydroxy compounds and/or their functional derivatives, and component C of diaryl carbonates or phosgene.
Examples of the component A are terephthalic acid, isophthalic acid, methyl terephthalic acid, methyl isophthalic acid, diphenyletherdicarboxylic acid, diphenoxyethanedicarboxylic acid, naphthalenedicarboxylic acid, and their ester-forming derivatives such as lower alkyl esters, phenyl esters, acid halides etc.
Examples of the component B are hydroquinone, resorcine, 2,2-bis(4-hydroxyphenyl)propane (bisphenol A), 4,4'-dihydroxydiphenyl, 1,1-bis(4-hydroxyphenyl)cyclohexane, 1,1-bis(4-hydroxyphenyl)ethane, bis-(4-hydroxyphenyl)methane, 2,2-bis(4-hydroxy-3,5-dibromophenyl)propane, 4,4'-dihydroxydiphenylsulfone, 1,2-bis(4-hydroxyphenyl)ethane and their ester-forming derivatives. The component B may be composed of one or more of the compounds listed above. Of the compounds, particularly preferred are bisphenol A.
Examples of the diaryl carbonates of the component C are diphenylcarbonate, dicresylcarbonate, di-β-naphthylcarbonate, bis(2-chlorophenyl)carbonate.
The polyester carbonate particularly preferred is a combination of terephthalic acid or diphenyl terephthalate ester, bisphenol A and diphenylcarbonate.
The said polyester carbonates preferably have the ratio of ester to carbonate of 1/9-9/1 and the ultimate viscosity of 0.4-1.1 as measured at 25° C. in a chloroform solvent. If the ultimate viscosity is over 1.1, shapability deteriorates. If the ultimate viscosity is below 0.4, mechanical properties are insufficient.
The polyester carbonates used in this invention can be produced from the above three components A, B and C by any methods such as bulk polycondensation, solution polycondensation, interfacial polycondensation, etc.
The aromatic polyester copolymers used in this invention are obtained by copolymerization of a mixture of terephthalic acid and isophthalic acid or their functional derivatives (having 9/1 to 1/9 of the molar ratio of terephthalic acid groups to isophthalic acid groups), and 2,2-bis(4'-hydroxyphenyl)propane (hereinafter referred to bisphenol A).
These aromatic polyester copolymers can be produced by known methods, for example, interfacial copolymerization (W. M. Eareckson. J. Poly. Sci. XL 339, 1959, Japanese Patent Examined Publication No.40-1959) wherein aromatic dicarboxylic chlorides solved in a water-insoluble organic solvent are blended and reacted with bisphenols solved in an alkali solution, solution polymerization (A. Conix. Ind. Eng. Chem. 51 147, 1959, Japanese Patent Examined Publication No. 37-5599) wherein aromatic dicarboxylic chlorides and bisphenols are reacted in an organic solvent, and melt polymerization (Japanese Patent Examined Publication No. 38-15247) wherein aromatic dicarboxylic acids and bisphenols are heated in the presence of acetic anhydride.
The mixtures of resin (B) used in this invention may consist of either two or three of polycarbonates, polyester carbonates and aromatic polyester copolymers which have compatibility with each other. Of the above mixtures, particularly preferable is the mixture consisting of 70-5% by weight of polycarbonates and 30-95% by weight of aromatic polyester copolymers because the mixture is excellent and well-balanced in transparence, strength, stiffness, resistance to methyl methacrylate and shapability and is superior in surface hardness and resistance to abrasion by tooth brushes.
The method of preparing the compound used in this invention from resin (A) and resin (B) is not critical.
Examples of compression molding for the inventive denture-base are a method comprising layering a plurarity of plate-like molds made of resin (A) and resin (B) approximating the size of an alveolar ridge, heating the molds to make them soften and then closing the top and bottom flasks to perform compression molding, and a method comprising heating a pre-formed two-layer or sandwitch-like mold having layers of resin (A) and resin (B) to make it soften and then perform compression molding. An example of injection molding for the inventive denture-base is a method comprising injecting resin (A) and resin (B) which have been melted in different cylinders into a sealed mold cavity simultaneously or alternately. Preferably employed is the method of compression molding using a plurarity of multi-layer molds made of resin (A) and resin (B), since the resultant denture-base is superior in resistance to acrylic monomers because of its multi-layer structure of resin (A) and resin (B).
Plate-like molds prepared from a blend or a mixture of granules or particulates of resin (A) and resin (B) in an extruder or a mixer such as a banbary mixer are not suitable to materials for the inventive denture-base. If such plate-like molds are employed, the resultant denture-base does not have gingiva-like appearance but has pearlescence or opacity due to scattering of visible radiations caused by the difference in refractive index between resin (A) and resin (B).
The state in the compound of this invention should not be a mixture or blend as mentioned above, but be a compound having integrated layers part of which may be blends of resin (A) and resin (B), since the latter state prevents scattering visible radiations, maintains transparency and has excellent bonding between resin (A) and resin (B) and other performances suitable to denture-bases.
The outer layer of the compound thus produced may be of resin (A) or resin (B), preferably, of resin (B), since resin (B) is excellent in compatibility with methyl methacrylate commonly used as repair resin and in bonding with artificial acrylic resin dentures compared with resin (A).
The compound of this invention preferably consists of 10-90% by weight of resin (A) and 90-10% by weight of resin (B), more preferably, 20-80% by weight of resin (A) and 80-20% by weight of resin (B) since the denture-bases with such proportion have excellent resistance to methyl methacrylate, isobutyl methacrylate, normalbutyl methacrylate etc. used as repair resins or relining resins and is excellent in properties such as appearance, strength, stiffness, etc.
Within the scope of this invention, one or more of ordinary additives such as antioxidants, heat stabilizers, ultraviolet absorbers, lubricants, mold release agents, dyes, pigments, colorants may be added to resin (A) and resin (B).
In order to more specifically explain this invention, specific examples are set forth hereinafter. However, it is noted that this invention is not limited by the specific examples set forth below.
EXAMPLE 1
Top and bottom flasks in which wax master models of denture-base having artificial teeth of acrylic resin (anterior and posterior teeth of acrylic resin manufactured by GC) were embedded respectively were heated to soften the wax and melt it away. Thereafter, a U-shaped mold (approxmating the size of an alveolar ridge and having the thickness of 3 mm) composed of a blend having the ratio of 7:3 of aromatic polyester copolymer colored in gingiva color (which was obtained by interfacial polymerization from terephthalic dichloride and isophthalic dichloride in the proportion of 1:1 in a methylene chloride solution and bisphenol A in an alkalic solution, and had 0.62 of logarithmic viscosity as measured in a phenol/tetrachloroethane (of 6:4 by weight) solvent) to polycarbonate (S 2000 manufactured by Mitsubishi Gas Chemical Co., Inc.) was placed on a gypsum mold in the bottom flask and was softened by blowing air heated at 340° C.
After the above mold softened well, a U-shaped mold colored in gingiva color consisting of polyether sulfone (Victrex® PES 4100G manufactured by ICI) was placed onto the above softening blend of polyester copolymer and polycarbonate and was softened by blowing air heated at 340° C. Thereafter, a U-shaped mold consisting of a blend having aromatic polyester copolymer and polycarbonate was placed onto the above mold of polyether sulfone and was heated to soften.
And other molds of polyether sulfone and of a blend having aromatic polyester copolymer and polycarbonate were respectively placed thereon and heated to soften in the gypsum mold in the bottom flask as mentioned above. After the five layers thus produced softened well, the flasks were closed to perform compression molding and then were left cooling in air. After having been cooled, the top flask was separated from the bottom flask to take out a denture-base product. The denture-base rigidly embedded the artificial teeth and had no sink marks and a size which corresponds faithfully to the wax master model.
The denture-base was made in contact with an repair resin for conventional acrylic denture-bases, that is, an instantaneous polymerizing resin (GC Revaron®) primarily based on methyl methacrylate by building up it onto the denture-base using ordinary brushing method. The denture-base was found to have no accident such as cracks.
Furthermore, a palatal portion of the denture-base was made in contact with a relining resin for acrylic resin denture-bases, that is, an instantaneous polymerizing resin (KooLiner® manufactured by Coe Co.) primarily based on isobutyl methacrylate by building up it thereon. The denture-base was found to have no changes such as cracks.
It is, therefore, observed that both of the above instantaneous polymerizing resins can be applied to the said denture-base.
COMPARATIVE EXAMPLE 1
A denture-base was obtained by the same compression molding as in Example 1 except that only U-shaped molds of polyether sulfone were employed in place of the U-shaped molds of polyether sulfone and of the blend having aromatic polyester copolyer and polycarbonate. However, artificial teeth were disengaged from the denture-base only by faintly pushing them.
The said denture-base made of polyether sulfone was made in contact with an instantaneous polymerizing resin (GC Revaron®) primarily based on methyl methacrylate by building up it thereon using a brush as in Example 1. The denture-base was found to have cracks in the portions such as those adjacent to artificial teeth where many residual strains occur.
In contact with an instantaneous polymerizing resin (KooLiner®) primarily based on isobutyl methacrylate, the denture-base was found to have no appreciable cracks.
COMPARATIVE EXAMPLE 2
A denture-base was obtained by the same compression molding as in Example 1 except that only U-shaped molds composed of a blend having aromatic polyester and polycarbonate in the proportion of 7:3 were employed in place of the U-shaped molds of polyether sulfone and of the blend having aromatic polyester and polycarbonate. The resultant denture-base rigidly embedded artificial teeth and was excellent in appearance.
The denture-base was made in contact with the two types of instantaneous polymerizing resins as employed in Example 1. In contact with the instantaneous polymerizing resin primarily based on methyl methacrylate, the denture-base was found to have no cracks. In contact with that primarily based on isobutyl methacrylate, it was found to have cracks which made it unsuitable for practical use.
EXAMPLE 2
A mold having the same U-shape as in Example 1 was obtained from polysulfone pellets (Udel® P1700 manufactured by UCC) and aromatic polyester copolymer pellets colored in gingiva color by use of a mixing injecting molding machines FSD-150 manufactured by Nissei Jushi. The proportion of polysulfone to aromatic polyester copolymer of the said mold was about 1:1. Since the molder has two cylinders from which each resin is injected into the die, the resultant mold was a compound which was not a complete mixture, but had integrated layers each resin.
A denture-base was obtained by the same compression molding as in Example 1 from the compounded U-shaped mold. The said denture-base had no problems such as sink marks.
In contact with the same instantaneous resin (GC Revaron®) primarily based on methyl methacrylate as employed in Example 1 and a relining resin (Parabase® manufactured by Kulzer Co.) composed of methyl methacrylate and about 30% of normalbutyl methacrylate, the denture-base was found to have no cracks and to be repaired well.
COMPARATIVE EXAMPLE 3
A denture-base was obtained by the same procedure as in Example 2 except that a U-shaped mold was prepared from only polysulfone in place of the compounded U-shaped mold in Example 2.
In contact with GC Revaron®, the resultant denture-base was found to have cracks.
COMPARATIVE EXAMPLE 4
A denture-base was obtained by the same procedure as in Example 2 except that a U-shaped mold was prepared only from aromatic polyester in place of the compounded U-shaped mold in Example 2.
In contact with Parabase®, the resultant denture-base was found to have cracks.
EXAMPLE 3
A denture-base was obtained by the same procedure as in Example 2 except that polyester carbonate (which was prepared by bulk polycondensation from terephthalic acid, bisphenol A and diphenylcarbonate, had the following formula as a basic structure: ##STR2## and had the ultimate viscosity of 0.655 as measured in chloroform solvent at 25° C., the m/n being 51/49) was employed in place of the aromatic polyester copolymer. The resultant denture-base had no problems such as sink marks.
In contact with an instantaneous resin (GC Revaron®) primarily based on methyl methacrylate and a relining resin (Parabase®) of methyl methacrylate and about 30% of normalbutyl methacrylate, the denture-base was found to have no cracks and to be repaired well.
COMPARATIVE EXAMPLE 5
A denture-base was obtained by the same procedure as in Example 3 except that a U-shaped mold composed only of polyester carbonate was employed in place of the compounded U-shaped mold in Example 3.
In contact with Parabase®, the resultant denture-base was found to have cracks. | A denture-base made of a thermoplastic resin compound which comprises polysulfone resins (A) and a resin (B) selected from the group consisting of polycarbonates, polyester carbonates, aromatic polyester copolymers and their mixtures, is excellent in mechanical properties and compatibility with acrylic resins, firmly implants artificial dentures of acrylic resin, and is readily repaired by use of repair materials of acrylic resin. | 2 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a dual pressure pump having at least one impeller producing two separate pressures in two separate chambers. The dual pressures are used for positive air pressure treatments in patients with sleep disorders. One pressure is used during inspiration and one pressure is used during expiration.
2. Description of the Related Art
There are many Bi-Positive Air Pressure (Bi PAP) devices used for treatment of sleep apnea, and other sleep disorders. These devices mostly use a variable speed motor with one blower to increase and decrease the air pressure applied to the patient or use valves to regulate the air pressure applied to the patient.
The devices with variable speed motors take a while to change the pressure applied to the patient, as the motor speed does not change instantaneously between the inspiration and expiration pressure settings. Similarly valves regulating the pressure in a chamber have a lag time while pressure is building up or reducing before it reaches the proper pressure to be applied to the patient.
U.S. Pat. No. 5,485,850 to Dietz issued Jan. 23, 1996 shows a Bi PAP device with two separate air supply sources at two different pressures.
A device is needed having one unit for supplying dual pressures to the patient such that there is always a ready supply of air at two different pressures to treat a patient.
SUMMARY OF THE INVENTION
The invention comprises a motor with at least one impeller. The impeller or impellers produce a different air pressure in different chambers. A hose transports the air from the chambers to the mask worn by the patient to deliver air at one pressure for use during inspiration and at another pressure during expiration. A valve selects which pressure to allow into the mask depending on if the patient is inhaling or exhaling. There is a means for detecting if the patient is inhaling or exhaling which regulates the valve. There are also means for measuring the airflow into and out of the patient.
A humidifier can adjust the humidity of the air being delivered to the patient.
Altitude adjustments are made to increase or decrease the impeller speed to deliver the correct air pressure to the patient.
The two chambers can have two pressures at adjustable ratios to adjust the inspiration and expiration pressures.
The patient can be monitored by a number of sensors for determining when the patient is inhaling or exhaling. The monitoring sensors can also measure a number of other parameters such as breathing rates, blood oxygen levels, stages of sleep, mask leaks, mask on or mask off, body position and movement of the patient, EEG, EKG, sounds such as snoring, and other information useful for sleep disorder diagnosis and treatment. The information obtained can be used in conjunction with adjusting pressures and times of delivery of air to the patient in real time, adjusting for mask leaks, storing information about the patient for diagnosis and long-term studies, or for alerting health care workers about the patent's condition requiring immediate action.
The sensors can trigger a mask off alarm or detect when the mask is put on to start the power for the motor to supply air to the patient.
A controller or microprocessor programmed to evaluate the data from the sensors on the patient, can make changes to the air pressure applied to the patient, and the timing thereof. The microprocessor can also store information for later reporting, transmit the data to recording equipment, or alert health care workers of the patient's condition.
Displays can provide data for the number of hours the motor has been on or other data of interest to the operator.
Data cards for input or output of data may be used. Data from the data card may be sent to a remote site by telemetry, telephony or by mailing the data card.
The device may be equipped with anti-rebreathing sensors and apparatus to ensure fresh air inspiration.
The device is portable, light weight and easy to use by a patient without the assistance of a health care provider such that the device can be used at home and monitored at a remote location.
OBJECTS OF THE INVENTION
It is an object of the invention to provide a dual air pressure pump with one motor having at least one impeller.
It is an object of the invention to provide accurate pressure control for inspiration and expiration gas delivery pressures.
It is an object of the invention to provide fast transitions between inspiration and expiration pressures delivered to the patient.
It is an object of the invention to provide a portable BiPAP device. It is an object of the invention to provide a multiple purpose device for BiPAP, CPAP, VPAP, SPAP, PPAP and AutoPAP applications.
It is an object of the invention to add humidity to the pressurized air.
It is an object of the invention to monitor the patient.
It is an object of the invention to measure airflow to and from the patient.
It is an object of the invention to record patient data for diagnosis and treatment.
It is an object of the invention to provide data storing cards for use in the device.
It is an object of the invention to communicate patient condition to remote monitoring equipment and personnel.
It is an object of the invention to treat a variety of sleep disorders with a variety of treatments with one device.
It is an object of the invention to provide options for several different treatment protocols on one device.
It is an object of the invention to provide adjustable settings for individual patient needs and comfort while using the device.
It is an object of the invention to provide long term monitoring data of one or more patients for medical studies.
It is an object of the invention to display data about the patient or devise for ease of reference.
It is an object of the invention to provide variable ratios of air pressure for inspiration and expiration.
Other objects, advantages and novel features of the present invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic showing the device with two separate air intakes and two separated impellers.
FIG. 2 is a schematic of a second embodiment showing the device with one air intake and two coaxial impellers.
FIG. 3 is a top view of the control panel.
FIG. 4 is a side view of a coaxial dual impeller blower in a housing as used in the schematic of FIG. 2 .
FIG. 5 is a cross sectional side view of one impeller in a housing with a bleed off slot.
FIG. 6 is a cross sectional side view of a movable position impeller in a housing.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
In treating patients having sleep disorders it is frequently required to administer a Bi-Positive Air Pressure (Bi PAP). In this treatment a first air pressure on the order of 20 cm H 2 O is applied to the patient during inspiration and a second pressure on the order of 3 cm H 2 O is applied to the patient during expiration. Preferably these pressures are adjustable for the needs of each individual patient. Referring to FIG. 1 a schematic of the system is shown wherein a gas delivery device 10 supplies gas at two different positive air pressures to a patient 100 . The gas delivery device 10 , preferably is small enough and light weight enough to be portable. The gas delivery device 10 has a carrying handle 11 to aid in transporting the device.
A portable gas delivery device may have a battery 150 for an internal power supply, a power cord 155 for an outside source of power, or both. The battery 150 may be rechargeable from the outside power source.
A motor 20 receiving power from the battery 150 or an outside power source through the power cord 155 turns shaft 22 . The motor 20 is preferably a brushless DC motor. Motor with brushes and a commutators produce ozone or NOx and other related particles which would be detrimental if added to the air of the breathing apparatus. The shaft 22 enters the pump housing 25 having a high pressure chamber 45 and a low pressure chamber 35 which are adjacent, having a barrier 40 therebetween. The shaft 22 turns high pressure impeller blades 46 in the high pressure chamber 45 and turns low pressure impeller blades 36 in the low pressure chamber 35 . The air intake aperture 142 for the high pressure chamber 45 has air filter 90 for filtering intake air stream 43 entering the high pressure chamber 45 . Similarly air intake aperture 132 for the low pressure chamber 35 has air filter 92 for filtering intake air stream 33 .
Alternatively the air intake can be a common air intake if the impellers 36 and 46 in FIG. 1 are turned around such that the air intake is between them and the air output would be to chambers which are separate.
The ratio of the high pressure in chamber 45 to the low pressure in chamber 35 is fixed by the relative size or position of the impeller blades. The ratio can be changed by varying a number of parameters including the relative size of the impellers, the gaps between the impellers and the housings, the size of the openings in the housings for admitting air from the impellers, or by other variables. The ratios may be adjustable or fixed. Generally for one patient the ratio of the inspiration pressure to the expiration pressure can remain fixed. It may be necessary to adjust the ratios for different patients or adjust the ratios for the same patient over time.
A humidifier 55 may be used to adjust the humidity of the air being supplied to the patient. The humidifier 55 , as shown in the dual pressure gas delivery device 10 , is in front of the high pressure air intake aperture 142 to supply moisturized air for inspiration. The humidifier 55 may be placed in other locations for supplying high pressure and/or low pressure moisturized air to the patient. A humidity control 140 to select the desired humidity is located on the control panel 110 and works in conjunction with humidity sensors 141 in housing 25 and the controller or microprocessor 82 to keep the humidity at a desired setting.
In a second embodiment shown in FIGS. 2 and 4 the motor 20 has a shaft 22 with impellers 136 of a first radius and impellers 146 of a second radius coaxially mounted on the shaft 22 . There is one air intake 144 to the impellers 136 , 146 for producing two streams of air, one at a high pressure, air stream 47 in chamber 45 and one at a low pressure, air stream 37 in chamber 35 . Since this embodiment has only one air intake 144 only one air filter 91 and one humidifier 55 are required. FIG. 4 shows a more detailed view of the motor 20 , high pressure impeller 146 and low pressure impeller 136 on shaft 22 in relation to housing 25 . The intake air 43 enters housing 25 . The low pressure impeller 136 discharges low pressure air 37 into low pressure chamber 35 and the high pressure impeller 146 discharges high pressure air 47 into the high pressure chamber 45 .
In a third embodiment, as shown in FIG. 5, the motor 20 has shaft 22 attached to impeller 146 . The housing has an annular slot 30 in the housing adjacent to impeller 146 to let air of a lower pressure into chamber 35 . Intake air 43 is acted on by impeller 146 creating a high pressure air 47 in chamber 45 and low pressure air 37 in chamber 35 . The annular slot 30 may be continuous or divided into sections.
The motor 20 in the three embodiments turns one or more impellers on shaft 22 for steadily supplying a high pressure air in the high pressure chamber 45 and a low pressure air chamber 35 . On one embodiment the motor speed is fixed to supply a constant pressure in the high and low pressure chambers 45 and 35 . In another embodiment a variable speed motor can be used to such that as the motor 20 speeds up or slows down a higher or lower volume of air is pumped and both the high pressure and low pressure are simultaneously adjusted upward or downward. A change in the motor speed can be used to make a pressure adjustment to the high pressure chamber 45 or low pressure chamber 35 when the ratio of the pressures is fixed but a variation or adjustment of the pressures in the chambers is called for. In this manner the high pressure and/or low pressure can be varied with changes in motor speed. Devices having one impeller and one pressure chamber would have to make large changes in motor speed and have a lag time to change speed and thereafter the pressure in the pressure chamber. A dual pressure impeller or two impellers with two pressure chambers do not require any motor speed change to change the pressure from high to low. However, adjustments to the pressure can still be effected by changing the motor speed.
In a fourth embodiment shown in FIG. 6 an actuator 300 moves actuation rod 310 up or down by a small distance as shown by arrows 315 . Actuator rod 310 is attached to slider 320 which moves up or down in housing 325 . Slider 320 carries motor 20 and impeller 346 up and down adjusting the clearance distance 350 between the impeller and housing 325 . With a larger clearance distance 350 the leakage rate of compressed air goes up reducing the air pressure in chamber 345 . With a smaller clearance distance 350 the air pressure in chamber 345 goes up. The air intake 43 supplies air for the impeller 346 to pump up to the desired pressure in chamber 345 . The actuator 300 can quickly and accurately adjust the clearance 350 between the impeller 346 and housing 325 thus quickly adjusting the pressure chamber 345 without changing the motor 20 speed.
The actuator 300 may be hydraulically, mechanically, electrically, electromechanically, or piezoelectrically driven. Any means for quickly and accurately moving the actuator rod 310 will allow the invention to be practiced.
The embodiment in FIG. 6 shows motor 20 on slider 320 however other embodiments where the motor is fixed and the actuator 300 only moves the impeller 346 are within the scope of the invention.
In all of the embodiments shown the motor 20 has shaft 22 connected to impeller an impeller, however in other embodiments the impellers can be on the outside of a rotating motor housing eliminating the need for a shaft 22 .
Altitude compensation is required for the impeller speed to increase or decrease to bring the pressure up to the desired level. A pressure altitude sensor 85 senses the altitude and reports it to the controller 82 , the controller then adjusts the motor speed accordingly. Altitude compensation can be controlled by a pressure transducer.
In the embodiments shown in FIGS. 1 and 2 if the pressure in the high pressure chamber 45 is kept at a pressure higher than needed for the patient 100 and the pressure in the low pressure chamber 35 is kept at a pressure higher than needed for the patient then a high pressure adjustment valve 49 and a low pressure adjustment valve 39 may be used to adjust the pressure of the air being delivered to the patient. The high pressure air flow 47 from the high pressure chamber 45 and the low pressure air flow 37 from the low pressure chamber 35 may thereby be regulated. The high and low pressure valves 49 and 39 respectively may be controlled by a controller or microprocessor 82 or set manually on control panel 110 as inspiration pressure control 120 and expiration pressure control 125 . Alternatively in another embodiment the motor 20 speed is adjusted to provide the desired pressure in the high pressure chamber 45 and in the low pressure chamber 35 eliminating the need for valves.
The outlet nozzle 48 is a split nozzle extending from the housing 25 over the housing barrier 40 such that both high pressure air 47 the adjacent low pressure air 37 flow in their respective halves of the nozzle to a split coupler 58 having two sides.
A dual pressure hose 50 connects to the coupler 58 . The dual pressure hose 50 has a high pressure side 51 and a low pressure side 52 for transporting the high pressure gas 47 and low pressure gas 37 to the mask 70 .
Alternatively the dual pressure 50 hose can be a small diameter hose inside of a larger diameter hose for transporting the separate pressures from the housing to the mask, or two separate hoses can be used.
A valve 60 at the entrance to the mask 70 alternately selects the high pressure air 47 or low pressure air 37 to be supplied to the patient 100 depending on if the patient is inhaling or exhaling. When the patient 100 is inhaling the valve 60 selector 62 blocks the low pressure air in the low pressure portion 52 of hose 50 and admits the high pressure from the high pressure portion 51 of hose 50 . Similarly when the patient 100 is exhaling the valve 60 selector 62 blocks the high pressure portion 51 of hose 50 and admits low pressure air. An actuator 63 moves the selector 62 based on information about the patient's breathing obtained from sensors 71 in the mask 70 and or sensors 80 placed on the patient 100 . The controller or microprocessor 82 determines when the patient 100 is inhaling or exhaling from the data provided and positions the actuator 63 accordingly by sending it signals over lead 83 .
The valve 60 may be a split butterfly valve, a gate valve or any other type of valve for selectively admitting only one pressure.
In one embodiment for controlling the pressure to the mask 70 a valve 60 such as a butterfly valve can be partially open to the high pressure chamber 45 and partially open to the low pressure chamber 35 simultaneously, resulting in a mix of between 0 and 100% of each pressure to select an intermediate pressure to the mask. The valve 60 can be quickly activated to any setting to provide any pressure between the high pressure in the high pressure chamber 45 and the low pressure in the low pressure chamber 35 .
Alternatively a hose 50 with one lumen can be used and the valve 60 for selecting high or low pressures can be at the outlet nozzle 48 . The hose 50 will then contain either a high pressure air flow 47 or a low pressure air flow 37 to the mask 70 .
The sensors 71 used for supplying information about the patient's breathing to the controller or microprocessor 82 may be imbedded in the perimeter of the mask 70 or on the mask surface. Such a mask 70 and the types of sensors used are described in the applicant's copending patent application titles Bio-Mask Ser. No. 09/465,054 filed Dec. 16, 1999 which is hereby made a part hereof and incorporated herein by reference.
In one embodiment a sensor 71 on the mask or in the dual pressure gas delivery device 10 can detect when breathing into the mask begins or when mask 70 is donned by a patient to automatically turn on the power to the motor 20 .
The sensors 71 can detect leaks or drops in pressure and send signals to microprocessor 82 to increase the pressure sent to the mask 70 to compensate for the leaks.
Sensors 71 can also detect the expiration gases to see if the patient is rebreathing his breath. The microprocessor 82 is programmed to adjust valves in the mask or pressures to the mask to prevent rebreathing.
Other sensors on the patient such as sensor 80 on the patient's chest may be used for supplying information about the patient's breathing to the controller or microprocessor 82 .
Some means for the detection of inspiration and expiration are shown in applicant's PCT applications WO 98/50095, entitled Controlling Gas of Drug Delivery to a Patient, international filing date May 7 1997, and in WO 97/16216 entitled Apparatus for Gas Delivery, international filing date Oct. 31, 1996. Other patents teaching breathing measurements are U.S. Pat. Nos. 4,440,177 and 4,463,764. All of the above patents and applications are attached hereto and incorporated herein by reference.
Other means for detecting breathing are by measuring air flow movements to the mask 70 from the air supply such as sensors like 195 placed at the entrance to the mask 70 . The sensors 195 may be laser sensors, radar Doppler sensors, ultrasonic sensors, ultrasound techniques, pitot tubes, or other electronic or mechanical means for measuring the air passing the sensor. Other means for measuring air flow rates and breathing are available such as shown in U.S. Pat. No. 5,038,733 entitled Flow Meter System issued Aug. 13, 1991 and U.S. Pat. No. 4,796,639 entitled Pulmonary Diagnostic System, issued Jan. 10. 1989 both of which are attached hereto and made a part hereof by reference.
The dual pressure gas delivery device 10 can be used to select only high pressure gas at all times to provide treatment of Continuous Positive Air Pressure (CPAP) with CPAP protocols. Similarly, with suitable programming of the controller 82 , the dual pressure gas delivery device 10 can be used for Variable Positive Air Pressure (VPAP) treatment protocols, Sleep linked Positive Air Pressure (SPAP) treatment protocols, Proportional Positive Air Pressure (PPAP) treatment protocols, Auto Positive Air Pressure (AuotPAP) or other treatment protocols by using the protocol selection feature 175 on the control panel 110 and having the controller 82 programmed for delivering gas at the proper gas pressures at the proper times.
In some treatment protocols there is a ramp time where the pressure is slowly increased to the desired pressure for treatment over time as the patient falls asleep. The dual pressure gas delivery device 10 has a controller/microprocessor 82 which can be programmed for ramp times and pressures as required by the patient. A ramp time control knob 130 on the control panel can also be used to select the ramp times. Ramp delay times are used in conjunction with ramp times. The ramp delay times allow a time before the ramp up of pressure begins, allowing the patient to fall asleep before the treatment begins. The ramp delay times can be selected on the control panel 110 by ramp delay time control selector 135 .
The ramp times, ramp delay times and other parameters can be programmed into the controller/microprocessor 82 by means of information stored on a data card 210 inserted into a data card port 115 . Alternatively the controller/microprocessor 82 may be programmed by a computer 200 and the information transferred to the controller/microprocessor 82 through computer input output plug 118 . The computer 200 may be remotely located at a hospital or sleep clinic and connected through the internet by wire or wireless phone systems or positioned adjacent the dual pressure gas delivery device 10 .
Alternatively a keypad 173 can be used to enter data into the microprocessor/controller 82 for patient data information, or to select times, pressures or other parameters for running the dual pressure gas delivery device. A menu on display 170 driven by controller 82 may prompt the user to enter data for settings by use of the keyboard 173 .
Other settings on the control panel 110 are for comfort settings 180 in which the temperature, pressure, humidity and timing of the application of pressurized air to the patient is controlled. The comfort setting may also be stored on the data card 210 or in the controller 82 , or computer 200 to provide the best comfort setting for the type of treatment individualized for the patient.
The control panel 110 or other portion of the device can have an on off switch 190 easily accessible by the patient for turning the device 10 on and off.
The control panel can have a display panel 170 such as an LCD for displaying information about the patient, the performance parameters of the dual pressure gas delivery device 10 , such as an hour meter for how long the motor 20 has been on, an elapsed time at pressure meter, an elapsed running time meter or other information. Such information can be selected for display by a selection button on the control panel 110 , by a touch screen LCD or by other means. The information selected can be transmitted from the controller/microprocessor 82 , to the display panel 170 or can be recorded or stored on a smart card 210 or the microprocessor 82 and can be transmitted to a computer 200 .
Different sleep disorder treatments use different trigger points to start the application of the high pressure during inspiration. A spontaneous trigger point measures the patient's spontaneous respiratory effort to trigger the application of gas to the patient when he starts to inhale. A timed trigger point uses a predetermined rate to trigger the application of gas to the patient.
Adjustable trigger points can be set in the controller 82 or on the control panel 170 to vary the pressures at which the patient begins to receive air either during inspiration or expiration
Poor synchronization between the patient's and the machine's ‘breathes’ lead to an unwanted increase in the work of breathing by the patient, reduced comfort and, subsequently detrimental/reduced therapy. Therefore it is important to have sensors 71 , 80 providing data to a controller 82 for application of the proper pressure at the proper time to treat the patient 100 . It is also important in BiPAP applications for the air supply to be at the right pressures in the mask 70 at the right time. In order to accomplish this one motor 20 spinning at one rate can supply two pressures to a mask 70 with a selector 62 alternating between the high and low pressures as the patient inhales and exhales. The motor speed can be increased or decreased to provide higher or lower pressures for inhaling and exhaling.
Communications from the sensors 71 , 80 can be by leads 83 , 81 respectively or by telemetry to the controller 82 .
The controller 82 can be programmed remotely by telemetry, through transmitter receiver 87 , or by wire to a port 118 to plug in a data line from a computer 200 to the controller 82 . The controller 82 can also be programmed by a data card 210 inserted into data card port 115 to transfer instructions to the controller 82 .
The port 118 can also be used to receive data from the controller 82 obtained from the sensors 71 , 80 and send it to the computer 200 for use by health care workers.
For example the sensors 71 , 80 may collect data about breathing volumes, breathing rates, breathing times, blood oxygen, EEG, EKG, EOG, EMG, patient pulse, patient temperature, snoring, position of the patient, sleep stages, patient movement, mask pressures, mask leakage, and other relevant data such as would be collected for a Polysomnogram (PSG). Such data for treating the patient may be sent by leads or by telemetry to the controller 82 for processing and storage. Patient data may be used to treat the patient in real time or be stored and studied at a later time. The data may be transmitted to a computer 200 at a remote location such as a doctor's office or hospital for remotely monitoring the patient. The computer 200 can store data about the patient which can be presented to a health care provider to diagnose or treat the patient. The data stored about a patient can be used over long term studies and can print out progress reports about the patient. Further is a patient is taking part in a study with a group of other patients the data is readily available to be used in the data for the study.
Connections to the computer 200 can be by telemetry such as by Blue Tooth®, a cell phone data transmittal protocol, or over telephony networks through data port 118 .
Telemetry devices used to transmit and store multiple channels of data are available under the trade name Siesta® by Compumedics Inc. Abbotsford, VIC, Australia.
The dual pressure gas delivery device 10 is preferably compatible with Telemed® or other remote medical systems such that the patient can use the dual pressure gas delivery device 10 at home and still have the support of health care providers located remotely. This device will help free sleep disorder patients from having to be at a hospital or other health care facility while being treated or tested.
Other means for data storage are by a data card or smart card 210 which can store data about a patient, or provide data about the patient or for programming the controller 82 . The data card or smart card is inserted into card port 115 to access the dual pressure gas delivery device 10 .
Input means for data or selections to control the dual pressure gas delivery device 10 through control panel 110 can be by selecting settings from any array of control knobs on the control panel 110 , by a menu driven touch screen on display 170 in conjunction with controller 82 , or by other input/output devices as are currently known and used in the art.
A sensor or sensors in or on a mattress the patient is on may be connected to the controller 82 to provide data about patient movements and activity rates.
There is a need for a mask off alarm or mask leak alarm to tell the patent or health care worker that the mask is not delivering air to the patient properly. Such detectors are taught in the patents incorporated herein by reference. When the mask off or mask leak alarm 165 is activated the mask should be checked and the alarm deactivated. Sensors 71 in the mask 70 can detect if the mask has come off of the patient and send a signal to the microprocessor 82 . The microprocessor can sound an alarm 165 or alert a health care worker that the mask is off. The microprocessor 82 may shut down the motor 20 if mask 70 is off.
The dual pressure gas delivery device 10 can be used for monitoring and treatment of many sleep disorders. The computer 200 , microprocessor 82 or data card 210 can store date about the duration, start times and stop times of the treatment, the pressures used, air flow rates and patient data such as heart rates, blood oxygen rates, snoring, patient movement and other polysomnogram data useful in diagnosing and treating patients.
Obviously, many modifications and variations of the present invention are possible in light of the above teachings. It is therefore to be understood that, within the scope of the appended claims, the invention may be practiced otherwise than as specifically described. | A gas compression and delivery device for treatment of sleep disorders. The device has a motor, at least one impeller, and two air pressure chambers, each receiving air at a different pressure, one pressure applied to a patient during inspiration and one for expiration. A mask having a dual pressure gas delivery hose and a selector for letting in either the high or low pressure gas depending on the breathing cycle of the patient. The gas pressures are adjustable by means of valves on the separate chambers in the device. At least one sensor on the patient sending data to a controller in the device as to the patient's physiological data which is used to determine the patients breathing treatment needs. The controller may be a microprocessor with memory capability to store patient data for diagnosis and treatment of the patient. Telecommunications by telemetry, or telephony to a remote site allows home use of the device rather than institutional use with health care providers on site. A data card may be used to input and or store data in the device. The controller is capable of instructing the device to treat the patient with a number of different protocols and record the patient's physiological data for diagnosis and treatment purposes. | 0 |
FIELD OF THE INVENTION
The present invention relates to a method and apparatus for removing at least one item of media wrapped around a rotating drum. In particular, but not exclusively, the present invention relates to the removal of currency notes from a rotating support structure using a scraper which is continually and automatically located at an optimum location for scraping items of media off the support.
BACKGROUND TO THE INVENTION
As the bank branch becomes a primary delivery channel for financial institutions, there is a constant need to improve operational efficiency and provide users with an improved quality of service. Most financial institutions have in the past had a defined system in place determining how currency notes were physically handled in a branch. Typically, there has been a secure vault where bulk currency notes are stored and these are distributed after multiple counts to tellers who can then perform necessary cash transactions with customers. Likewise, when cash has been received from customers, this has been counted many times and eventually returned as incoming cash to a vault. It has thus not been uncommon for currency notes to be counted by hand many times on a journey through a branch. Such cash handling procedures have decreased employee efficiencies and increased customer wait times. There has thus been a need to reduce exposed currency notes in a branch.
As technology has improved, attempts have been made to automate certain aspects of the currency note handling process. Such technology allows for remote note imaging or check imaging, signature capture and other such verification steps. The development of such technology has led to the introduction of media depositories used in automated teller machines (ATMs) and other such self-service terminals. Media depositories are used to receive media items from a customer. One common type of media depository is a sheet media depository for receiving items of media in sheet form. For example, such items of media can be currency notes, checks, tickets, gyros or the like. Some sheet depositories are capable of receiving a bunch of sheet items of media in a loading area and then picking individual sheets from a bunch so that each sheet can then be identified and validated individually prior to storage of a validated sheet within a depository or returned to a customer.
Another type of automated unit is the currency recycler. In such devices, customers may deposit items of media such as currency notes, checks, vouchers or the like, and these are processed separately one-by-one and stored in various storage modules within a terminal. For example, a storage unit can be an escrow storage unit in which, instead of being deposited directly into a storage module, once counted and verified, currency notes or checks input by a user are held temporarily until a teller negotiating with a user completes a transaction. If a customer decides to cancel a transaction or asks for the items to be recounted, the original deposited bank currency notes can be returned. This function allows any disputes to be resolved promptly. The temporarily stored items are held in a roll storage module (RSM) in the escrow module.
Cash recyclers and other such units also include one or more roll storage modules (RSMs). Such RSMs are provided for each of the possible currency notes or checks or other such vouchers which may be presented at a recycler unit. For example, an RSM dedicated to a £10 note will be provided as well as an RSM dedicated to a £20 note as well as an RSM dedicated to a £50 note or the like.
When a customer presents a bunch of items, these do not need to be manually counted by a teller, but are instead fed into an input slot on the recycler unit. Each presented item is counted and verified within a recycler and once it has been decided to make a permanent deposit of the presented items, the items are separated and stored in a respective RSM. For example, all £20 notes presented in a bunch are stored in the £20 RSM etc.
A cash recycler thus helps automate acceptance, authentication and validation of currency notes. Another advantage of such units is that the deposited items which are stored in respective RSMs can subsequently be dispensed when another user attends at a teller and requests currency notes. A cash recycler thus enables previously deposited currency notes to be instantly available for dispensing to customers.
Cash recyclers also help reduce transaction times and time taken for start and end-of-day cash balancing. Average wait times for customers can thus be reduced and overall branch security is improved.
In an RSM, items of media are wrapped around a cylindrical drum. The drum thus presents a curved outer surface and the items are bent around the outer surface and located and kept in place by one or more tape windings.
It is understood that there are other self-service terminals and other item storage devices where sheet items of media are stored on a semi-permanent basis for subsequent dispensation of the stored items to a user requesting them. On many occasions the rolled storage units utilized can store items for many hundreds, if not thousands, of hours. Often the storage occurs in such a way that the items are quite tightly wrapped, and thus curved. Being stored in such a state and for such a long period of time can make it extremely difficult on occasion to remove the items from a storage reel.
This problem is particularly pronounced when the storage drum used is used to store a large number of items. In such instances, the effective outer diameter of a storage drum and windings can be radically enlarged relative to the diameter of the drum in an empty state. Known techniques for scraping items of media from a rotating drum so as to assist the removal of the items are not able to cope with such large quantities as the expanding diameter interferes with the operation of the scraper. In particular, when storing many hundreds of notes, a drum diameter and thus a tangential angle of items leaving the effective outer surface of the drum becomes too great and the scraper is effectively pushed out of a desired location.
This has two detrimental effects. Firstly, a blade edge is no longer duly located to scrape items to release them from the drum. Also, items which are removed cannot access and move along a desired pathway to an exit orifice. The pathway is blocked by the expanded drum/windings.
SUMMARY OF THE INVENTION
It is an aim of the present invention to at least partly mitigate the above-mentioned problems.
It is an aim of certain embodiments of the present invention to provide an apparatus and method which can continually and automatically assist in the removal of items of media from a rolled storage drum.
It is an aim of certain embodiments of the present invention to provide a method and apparatus that provides a system of removing stored items from an RSM regardless of the number of stored of items. The system is thus able to store many hundreds or even thousands of items.
According to a first aspect of the present invention there is provided apparatus for removing at least one item of media from a rotating drum element, comprising:
a scraper element comprising a blade edge region locatable at an effective outer surface of a rotating drum element; and a scraper element support that locates the blade edge region at a desired position at the effective outer surface; wherein the scraper element rotates and moves laterally with respect to the support responsive to a diameter of the effective outer surface.
Aptly, the effective outer surface comprises an outer surface of the drum element or an outer surface of a tape element wrapped around the outer surface of the drum element.
Aptly, said a desired position comprises location of the blade edge region at a proximity and orientation with respect to the effective outer surface whereby a blade tip of said blade edge region almost engages the effective outer surface and an abutment surface of the blade region terminating in the blade tip has a desired angle of attack relative to a tangent of the effective outer surface.
Aptly, the blade edge region is continually located at a respective desired position automatically as items of media are added to or removed from the rotating drum element.
Aptly, the support comprises a first and further spaced apart substantially parallel plate element, each comprising a respective elongate plate aperture into which a respective end of a shaft element supporting the scraper element is rotatably mounted.
Aptly, the first and further plate elements rotate in common at a respective first end region thereof about a support axis of rotation and the support further comprises a riding roller element urged against said effective outer surface to ride thereon; wherein the support plate elements rotate responsive to a location of the riding roller element.
Aptly, at least one wall member comprises an elongate wall aperture, an end of said shaft element being rotatably mounted in the wall aperture and a respective one said plate aperture; wherein a longitudinal axis of the wall aperture and a longitudinal axis of the respective one plate aperture are angled apart to lock the shaft element at a position respective to a diameter of the outer surface.
Aptly, the scraper support comprises at least one elongate aperture that locates an end of a shaft carrying the scraper element wherein the shaft end locates along the aperture responsive to said a diameter to thereby provide lateral movement of the scraper element with respect to the support.
Aptly, the scraper support comprises at least one aperture that locates an end of a shaft carrying the scraper element wherein the shaft end rotates in the aperture responsive to said a diameter to thereby provide rotational movement of the scraper element with respect to the support.
Aptly, the scraper support comprises at least one elongate aperture associated with a longitudinal axis that locates an end of a shaft carrying the scraper element and an adjacent wall element comprises an elongate aperture associated with a respective longitudinal axis angled with respect to said a longitudinal axis that locates said an end, wherein the shaft locates at a crossover point of the apertures responsive to said a diameter.
According to a second aspect of the present invention, there is provided an automated teller machine (ATM) comprising an escrow container which comprises apparatus for removing at least one item of media from a rotating drum element, comprising:
a scraper element comprising a blade edge region locatable at an effective outer surface of a rotating drum element; and a scraper element support that locates the blade edge region at a desired position at the effective outer surface; wherein the scraper element rotates and moves laterally with respect to the support responsive to a diameter of the effective outer surface.
According to a third aspect of the present invention, there is provided a method for removing at least one item of media from a rotating drum element, comprising:
locating a scraper element support responsive to a diameter of an effective outer surface of a rotating drum element; and locating a blade edge region of a scraper element supported by the support at a desired position at the effective outer surface by rotating and moving the scraper element laterally with respect to the support responsive to said a diameter.
Aptly, the method includes continually locating the blade edge region at a respective desired position automatically.
Aptly, the method further includes the step of locking motion of a shaft element supporting the scraper element at a pre-determined position with respect to the support, said pre-determined position being variable responsive to the diameter of the effective outer surface.
Aptly, the method further comprises wrapping an item of media or removing a wrapped item of media at the effective outer surface of the rotating drum element thereby changing the diameter of the effective outer surface; as the diameter changes, unlocking the shaft element; locating the shaft element at a new pre-determined position responsive to a new effective diameter; and locking motion of the shaft element at the new pre-determined position.
Aptly, the method further comprises locating the scraper element support by urging a riding roller element on the support against the effective outer surface; and rotating plate elements of the support about a support axis of rotation as the roller element moves towards or away from a central axis of rotation of the drum element.
Aptly, the method further comprises wrapping at least 400 items of media one-by-one around the rotating drum element.
Aptly, the method further comprises unwrapping pre-stored items of media one-by-one from a rotating drum, removal of each item being facilitated by locating a scraper at a lift off location and at a desired angle of attack with respect to a next item to be removed that is wound on the rotating drum.
According to a fourth aspect of the present invention there is provided a self-service terminal or cash recycler or teller assist unit comprising apparatus for removing at least one item of media from a rotating drum element, comprising:
a scraper element comprising a blade edge region locatable at an effective outer surface of a rotating drum element; and a scraper element support that locates the blade edge region at a desired position at the effective outer surface; wherein the scraper element rotates and moves laterally with respect to the support responsive to a diameter of the effective outer surface.
According to a fifth aspect of the present invention, there is provided apparatus for removing at least one item of media from a rotating drum element, comprising a scraper element comprising a blade edge region locatable at an effective outer surface of a rotating drum element and a scraper element support that locates the blade edge region at a desired position at the effective outer surface responsive to a diameter of the effective outer surface.
According to a sixth aspect of the present invention, there is provided apparatus for removing at least one item of media from a rotating drum element, comprising a scraper element comprising a blade edge region locatable at an effective outer surface of a rotating drum element and a scraper element support that locates the blade edge region at a desired position at the effective outer surface responsive to a diameter of the effective outer surface wherein an abutment surface of the blade region is continually located substantially at a pre-determined angle of attack relative to a tangent of the effective outer surface independent of the diameter.
According to a seventh aspect of the present invention there is provided apparatus for removing at least one item of media from a rotating drum element, the apparatus comprising:
a scraper support defining a slot;
a scraper including (i) a blade edge region locatable at an effective outer surface of a rotating drum element, and (ii) a mounting shaft slidably located in the slot and operable to rotate and slide within the slot in response to changes in a diameter of the effective outer surface of the rotating drum element.
Certain aspects of the present invention provide the advantage that large numbers of items of media may be stored in an RSM and subsequently removed as required.
Certain aspects of the present invention provide the advantage that a scraper element used to assist during the removal of previously wrapped items of media is automatically and continually located at an optimum position with respect to a rotating drum. The scraper element may be located at a desired lift off position and at an angle of attack with respect to a tangent to the effective outer surface of a rotating drum so that items of media are lifted from the drum at an outer peripheral edge thereof.
Certain embodiments of the present invention provide a very compact storage module which is able to fit many items of media in a stored state for a given volume of space. Certain embodiments of the present invention continually and automatically locate a scraper used to remove items of media in such a way that the scraper does not become unduly sharp which would otherwise cut or tear items of media or tape used to store items of media in a RSM.
Certain embodiments of the present invention provide an RSM able to store more than 1000 items of media.
BRIEF DESCRIPTION OF DRAWINGS
Embodiments of the present invention will now be described hereinafter, by way of example only, with reference to the accompanying drawings in which:
FIG. 1 is a schematic diagram of a teller assist unit according to an embodiment of the present invention;
FIG. 2 is a schematic diagram showing a scraper element and a scraper element support located with respect to a rotating storage drum;
FIG. 3 illustrates location of a scraper element with respect to a near empty rotating storage drum; and
FIG. 4 illustrates location of a scraper element and support with respect to a nearly full rotating storage drum.
DESCRIPTION OF EMBODIMENTS
In the drawings like reference numerals refer to like parts.
FIG. 1 illustrates a teller assist unit 100 according to an embodiment of the present invention. It will be understood that certain embodiments of the present invention are not restricted to storage units within a teller assist unit but optionally may be used in automated teller machines (ATMs), cash recyclers, vending machines or the like wherever sheet items of media such as currency notes, checks, vouchers, pages or the like are to be stored and/or deposited. The teller assist unit 100 includes a secure housing 101 which includes a top wall 102 and floor standing wall 103 , together with a back wall 104 and a front fascia wall 105 . The front fascia includes a bill, entry/exit slot 106 at which a user can present a bunch of currency notes or checks or single currency notes or checks or other such items of media for deposit. The bill entry/exit slot 106 is also the outlet slot whereby items of media such as currency notes and/or checks are returned or are dispensed to a user dependent upon a user requirement. In the instance of a teller assist unit, the user is a teller of a bank branch or other such authorized user who acts as an interface with a bank customer. Currency notes or checks deposited are validated by a bill validator 107 , as will be understood by those skilled in the art. A bill transport path 108 which includes one or more rollers and/or endless belts is used to locate items of media one-by-one at a desired roll storage module 120 .
In addition to handling deposits the teller assist unit can be utilized to dispense currency notes which are stored in the roll storage modules. For example, if a teller requires £120 worth of currency notes, this information may be input at a user interface (not shown) on the front fascia 105 of the teller assist unit and then a central processing unit (not shown) initiates selection of currency notes from one or more roll storage modules. For example, to dispense £120, the roll storage module (RSM) which holds £20 notes may be placed in a dispense mode of operation in which six previously stored £20 notes are dispensed from the RSM onto the bill transport path 108 . A bill return path module 125 is utilized to locate dispensing items from the bill transport path 108 to the exit slot 106 . It will be understood that rather than dispensing six £20 notes from a single RSM, the teller assist unit may be selectively operated to dispense two £50 notes form a £50 note RSM and two £10 notes from a £10 note RSM. Other combinations are of course possible.
FIG. 2 illustrates parts of an RSM 120 . Each RSM includes a secure box formed form a back plate 200 which is spaced apart from, and substantially parallel with, a front wall 201 (not shown). The front and back walls are closed by opposed end walls and top and bottom walls (also not shown).
The RSM also includes a rotatable drum 201 . This has a substantially cylindrical outer surface 202 and is arranged to rotate about a longitudinal rotation axis. The drum is driven by a drive motor and drive system (not shown).
In use, a pair of tapes, which may be separate tapes or portions of a single continuous tape, are secured to an outer surface 202 of the drum and are continually wrapped around the outer surface of the drum. Thus, with the tapes unwound an effective outer surface of the drum is provided by the cylindrical outer surface. As the tapes are wound around the outer surface of the drum an outermost winding of the tapes provides an effective outer surface of the drum. A diameter of the effective outer surface of the rotating drum will thus vary depending upon the number of windings of tape.
Items of media such as currency notes or the like are wrapped around the curved cylindrical surface of the drum by being sandwiched between the two tapes as the tapes are wound onto the drum. Thus, over time, as items of media are stored on the drum, the outer diameter increases with currency notes being wound one after another at pre-determined locations and a pre-determined circumferential distance apart on the drum. The notes are sandwiched between tape.
In order to assist the removal of items of media which have been stored on the rotatable drum, a scraper 205 is provided. This scraper 205 includes a blade edge 206 and a scraper body 207 that is secured to a shaft 208 . The shaft 208 has a first end 209 which is located in an elongate aperture 210 in a side wall 211 of a skid plate 212 . The skid plate provides a substantially shovel-like platform including a base plate 213 and a further side wall 214 . The further side wall 214 also includes an elongate aperture 215 which has a similar size, dimension and shape as the aperture 210 in the first side wall 211 which is spaced apart from and substantially parallel with the further side wall 214 . A further end 216 of the shaft 208 which supports the scraper is located in the further aperture 215 in the further side wall 214 . The skid plate 212 including the base plate 213 and the opposed side walls 211 , 214 rotate as a single piece about a pivot point indicated by the position of a hole 220 in the first side wall 211 and a further hole 221 in the further side wall 214 . Whilst an end of the skid plate 212 thus pivots up and down, a remaining end is free. This free end of the skid plate is urged by a spring or other such biasing element (not shown) towards the outer surface of the drum. The free end also includes a roller which rides on the effective outer surface of the drum. That is to say, when the drum is empty the roller rotates and rides on the cylindrical outer surface of the drum, whilst when one or more windings or tape are wound around the drum the roller rolls on an outer surface of an outermost winding of an outermost tape. Thus, as an outer diameter of an effective outer surface of the drum increases or decreases, the roller which is caused to be constantly and automatically urged against the effective outer surface by the spring, causes the skid plate 212 to pivot constantly so as to be located at a desired position with respect to the drum which is dependent upon the diameter of the effective outer surface.
The back plate panel 200 also includes an elongate aperture (partly shown) 230 . This aperture has a similar shape, that is to say an elongate rectangle with rounded ends, as the elongate apertures 210 , 215 in the side walls of the skid plate. However, a longitudinal axis of the aperture 230 in the back plate panel 200 is angled with respect to an elongate longitudinal axis associated with the apertures in the skid plate side walls. It will be understood that an opposing front plate panel of the RSM may optionally also have an appropriately angled elongate aperture. The elongate apertures in the front and back plate panels are a similar size and are angled at an identical angle with respect to a longitudinal axis of the apertures in the side walls of the skid plate.
FIG. 3 illustrates the location of a blade edge of the scraper and the skid plate for an empty or nearly empty drum. As illustrated in FIG. 3 , opposed rollers include an upper roller 300 and a lower roller 301 . One or both of these rollers is a driven roller so that items of media may be introduced through an entrance/exit orifice 302 in a deposit mode of operation. An incoming item of media 303 is shown in FIG. 3 . It will be understood that in a withdrawal mode of operation the rollers will rotate in an opposite direction and items of media will be removed from the drum along a similar path and out of the orifice 302 which thus acts as a port. (In this sense the item 303 shown in FIG. 3 could also show a location of an outwardly moving item).
As will be understood with respect to FIGS. 2 and 3 , the skid plate 212 is aligned to pivot about the same axis as the lower roller 301 . The base plate 213 of the skid plate is illustrated in FIG. 3 in a position which is inclined slightly upwards towards the free end of the skid plate above the horizontal. This is because a diameter of the effective outer surface of the drum is small (shown by radius r 1 ) and the roller 305 which is constantly urged against this surface, thus permits the skid plate to tilt upwards. With a relatively small diameter of an effective outer surface the shaft 208 is located so that an end 209 of the shaft is located towards an extreme end of both the elongate aperture 210 in the skid plate side wall and the elongate aperture in the back and/or front plate. The location of the shaft locates the scraper body 207 and the blade edge 206 located at an end thereof. The blade edge 206 is held in a position on or immediately proximate to the effective outer surface of the drum. That is to say, when the drum is empty the blade edge rides on the cylindrical outer surface of the drum or very proximate to it, and when a few windings or more are on the drum the blade edge rides on an outer surface of an outermost winding or very proximate to it.
An abutment surface 320 of the scraper extends from the blade edge 206 along a lower surface of the blade body. This abutment surface helps guide incoming items of media in a deposit mode of operation moving in a left to right motion in FIG. 3 . It is to be noted that in a withdrawal mode of operation, the abutment surface 320 also guides items of media as they are released from windings on the drum so as to direct the items of media to the port 302 .
FIG. 4 illustrates the position of the skid plate and drum when the drum is full or almost full. In this sense it is to be noted that a radius r 2 of the effective outer surface of the drum shown in FIG. 4 is substantially greater than the radius r 1 shown in FIG. 3 . In this sense the roller 305 which is fixed to the skid plate and is rotatable therewith and which rides on an effective outer surface of the drum locates the base plate 213 of the skid plate 212 in a slightly declined position with respect to the horizontal. As shown in FIG. 4 an item of media 303 which is incoming or outgoing at the port 302 follows a pathway towards the drum below an abutment surface 320 of the blade. This pathway remains open regardless of the diameter of the effective outer surface. This enables items of media such as currency notes or the like to be delivered at the port 302 , driven by opposed rollers 300 , 301 and driven along the pathway to a position where opposed tape windings will be wound onto an outermost surface of the drum. When the drum is empty the tape windings of a first winding will be wound onto the cylindrical outer surface of the drum. For subsequent windings the two tape elements which sandwich a currency note therebetween will be wound on top of an outermost surface of an outermost immediately preceding winding of tape.
As illustrated in FIG. 4 , as the base plate 213 of the skid plate is pivoted upwards or downwards dependent upon whether the diameter of the drum is increasing or decreasing, the position of the shaft, illustrated by the location of the end 209 of the shaft 208 in FIG. 4 , is also constantly and automatically changed. As shown in FIG. 4 , with the effective outer surface of the drum at or near to a maximum, the shaft end 209 is located at a lower end 400 of the angled elongate aperture in the side frame. Likewise, the shaft end 209 is located at a left hand side most (as shown in FIG. 4 ) end of an elongate slot 210 in the side wall 211 of the skid plate. It will be appreciated that the further end 215 of the shaft will be similarly located in elongate apertures in the first side wall 214 of the skid plate and the elongate aperture 215 in the back plate panel 200 . Despite the fact that an effective outer surface of the drum has changed with respect to FIG. 4 , it is noted that the blade edge 206 remains at a desired location with respect to the effective outer surface. That is to say, the blade edge remains riding on or very proximate to the effective outer surface. Also, the abutment surface 320 which guides items coming in or leaving the drum region is maintained at a desired location.
More particularly, the blade edge is located so as to scrape or otherwise remove items of media and tape of windings in a withdrawal mode of operation. Also, the abutment surface is angled with a desired angle of attack, relative to an effective tangential direction of the effective outer surface. That is to say, items of media being unwound (by rotating the drum clockwise as shown in FIG. 4 ) together with tape being unwound from the outermost surface of the drum and which leave the drum following a trajectory of a tangent to the effective outer surface. This means they meet with a duly aligned blade edge and abutment surface so as to help facilitate easy onward motion of the off coming items.
Embodiments of the present invention may provide a single tape escrow or other such roll storage region which utilizes a scraper to help remove notes, particularly tightly curled notes, from a drum and thereafter onto a transport system. The scraper is maintained in contact with an effective outer surface of the drum and is very close to or perfectly aligned with the tangential direction of the tape/notes being removed from a rotating drum. This ensures that all types of note conditions are removed from the drum.
Aptly, 500 or more items of media such as currency notes or the like may be stored in the storage module. Aptly, 1000 items of media such as currency notes or the like or more are stored in the storage module.
Certain embodiments of the present invention provide a scraper which is moved further back as an effective drum diameter increases whilst still ensuring that the scraper tip is very close to a lift off position where a next item of media is being removed from a roll. This is achieved by having a scraper shaft, which supports a scraper blade, pass through a parallel hole in a skid plate and continuing through a corresponding angled slot in an adjacent frame of a storage module. The skid plate is pulled by an urging mechanism such as one or more springs against the drum with a skid plate roller always in contact with the drum. As a result, as an effective drum diameter increases or decreases, the skid plate supporting a scraper moves accordingly. As the skid plate rotates with increasing drum diameter, the scraper shaft is forced along the profile of the two slots until it becomes locked. The two slots are angled with respect to each other so that the open space for the scraper shaft reduces, thus causing the scraper shaft to be locked for any one particular given diameter. The action of the two slots causes the scraper to be automatically and continually moved backwards and forwards for any given drum diameter.
Throughout the description and claims of this specification, the words “comprise” and “contain” and variations of them mean “including but not limited to” and they are not intended to (and do not) exclude other moieties, additives, components, integers or steps. Throughout the description and claims of this specification, the singular encompasses the plural unless the context otherwise requires. In particular, where the indefinite article is used, the specification is to be understood as contemplating plurality as well as singularity, unless the context requires otherwise.
Features, integers, characteristics or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith. All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of the features and/or steps are mutually exclusive. The invention is not restricted to any details of any foregoing embodiments. The invention extends to any novel one, or novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.
The reader's attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference. | An apparatus and method are disclosed for removing at least one item of media from a rotating drum element. The apparatus includes a scraper element comprising a blade edge region locatable at an effective outer surface of a rotating drum element and a scraper element support that locates the blade edge region at a desired position at the effective outer surface responsive to a diameter of the effective outer surface. The scraper element rotates and moves laterally with respect to the support responsive to the diameter. | 1 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims the benefit of the filing date of U.S. Provisional Patent Application No. 61/512,588 filed Jul. 28, 2011, the disclosure of which is hereby incorporated herein by reference.
TECHNICAL FIELD
[0002] The invention pertains to a flow body with a base body and a leading edge, as well as an aircraft with a flow body in the form of a wing.
BACKGROUND OF THE INVENTION
[0003] Wings of modern commercial aircraft and air freighters with a high take-off weight are subject to considerable requirements. On the one hand, the weight of the wing structure should be as low as possible, but the mechanical stability and elasticity should suffice for extreme flight maneuvers that are used as a design basis. A high reliability, as well as a particularly small number of individual parts, needs to be ensured in order to increase the safety of the aircraft and to improve the maintainability. In addition to stability and reliability aspects, the wing construction also needs to be as slender as possible in order to achieve the least possible drag, but still provide the greatest lift possible, wherein it is attempted to achieve a laminar flow, in particular, on the upper side of the wing.
[0004] A wing of a modern aircraft comprises at least one so-called wing box, in which several two-spar bending beams are arranged that are connected into a box-like element with the aid of ribs and by means of upper and lower shells that are reinforced with longitudinal reinforcing elements. This so-called wing box primarily serves for absorbing mechanical stresses during the flight. The upper and lower shell of the wing box are correspondingly shaped in order to achieve a desired aerodynamic behavior and supplemented with a rounded leading wing edge and a tapered trailing wing edge in order to form a complete profile with the least possible aerodynamic drag.
[0005] According to the prior art, there exists a variety of different connecting constructions for connecting leading wing edges to wing boxes. All these constructions comprise angle brackets, connecting bodies or similar elements that are connected to the wing box, as well as to the leading wing edge, by means of rivets or other connecting means. This results in, for example, a gap or a step being formed between an upper shell of the wing box and a skin panel of a leading wing edge, wherein this gap or step leads to a distortion of the laminar flow, in particular, at high flying speeds.
BRIEF SUMMARY OF THE INVENTION
[0006] An exemplary embodiment of the invention comprises a flow body with a base body and a leading edge that are connected to one another such that a reduction or elimination of all discontinuities is achieved in order to realize a laminar flow around the flow body. An advantage of the present invention can be seen in simplifying the installation of a flow body and in reducing the installation time.
[0007] According to an aspect of the invention, the flow body comprises a flow body base body with at least one first shell element and a leading flow body edge with at least one second shell element and at least one clamping body, as well as at least one receiving space that is partially delimited by at least one of the clamping bodies, wherein the flow body base body comprises on a front end at least one projection, the shape of which corresponds to that of the at least one receiving space such that the at least one projection can engage into the at least one receiving space, wherein the at least one clamping body is internally arranged on the leading flow body edge such that it is spaced apart from a rear end of the at least one second shell element, wherein the rear end of the at least one second shell element is flushly clamped on the at least one first shell element when the at least one projection engages into the at least one receiving space.
[0008] In the context of the invention, the flow body is considered to be an aerodynamically active body that may be realized, in particular, in the form of a wing of an aircraft. However, the invention is not limited to such wings, but rather generally defines an object that comprises a flow body base body and a leading flow body edge.
[0009] The flow body base body is considered to be the main component of the flow body that, for example, carries the mechanical loads and fulfills the required aerodynamic functions of the flow body with shell elements. The flow body base body comprises at least one first shell element that may consist, for example, of an upper shell or a lower shell, between which reinforcing elements or the like may extend. In this respect, it is not important whether it actually consists of an upper shell or a lower shell as long as the properties described below can be realized. The flow body base body comprises a receiving end, on which the leading flow body edge needs to be arranged and to which a projection is attached that allows a load introduction from and to the leading flow body edge.
[0010] The leading flow body edge comprises at least one second shell element that extends, for example, over a significant or the entire spatial extent of the leading flow body edge such that upper and lower shells do not necessarily have to be separated from one another. In fact, the second shell element may serve for realizing a continuous change in shape or direction of a surface from an upper shell to a lower shell. At least one clamping body that comprises a receiving space is arranged on the leading flow body edge, preferably on its inner side. The mounting of the clamping body on the leading flow body edge practically can be carried out in an arbitrary fashion and may be realized, in particular, by means of welding, bonding, laminating or other connecting methods in order to reduce the connecting means protruding into the flow. The second shell element preferably extends over the clamping body such that the receiving space is covered by an inner side of the second shell element.
[0011] The receiving space of the at least one clamping body is designed for enclosing the projection of the flow body base body in order to ideally produce a form-fitting connection therewith. The projection therefore is shaped such that it can be introduced into the receiving space in order to allow a force transfer from the leading flow body edge to the flow body base body and vice versa. In a connection between the leading flow body edge and the flow body base body, the second shell element flushly rests on the first shell element accommodating the projection due to the extent of the second shell element. This simultaneously allows a load transmission between the leading flow body edge and the flow body base body, wherein it is also possible to eliminate connecting means that extend through the shell elements and outward to the aerodynamically active surface, as well as to simultaneously reduce or entirely eliminate any type of gap or step due to the flush contact.
[0012] The term receiving space refers to a geometric shape that is suitable for receiving an object. For this purpose, the receiving space comprises walls that are open on at least one side in order to allow the insertion of the object. In the context of the invention, the object is a projection on the leading flow body edge such that the receiving space comprises an opening for the insertion of the leading flow body edge and has a depth that suffices for completely accommodating the projection.
[0013] In comparison with a conventionally manufactured flow body, the flow body therefore has the same aerodynamic qualities, but the number of components for connecting the leading flow body edge to the flow body base body is significantly reduced and the transition between the leading flow body edge and the flow body base body simultaneously is significantly improved with respect to aerodynamic aspects.
[0014] In an advantageous embodiment of the invention, the projection of the flow body base body is realized in the form of an angular deflection on the front end of the first shell element. This essentially means that a relatively small section of the first shell element is angled relative to the plane, in which the first shell element primarily extends. The angular deflection is characterized by a defined change of angle and the formation of a connecting link that can be introduced into a corresponding receiving space of the at least one clamping body. In this way, a force in the primary direction can be easily introduced into the first shell element.
[0015] In an advantageous embodiment of the invention, the leading flow body edge comprises several clamping bodies that are spaced apart from one another and extend in a common mounting plane. Consequently, the leading flow body edge can uniformly introduce a load into the flow body base body along a mounting plane by means of a plurality of individual clamping bodies such that no jamming or impermissible mechanical stress on the first shell element occurs depending on the number of clamping bodies used.
[0016] In a likewise advantageous embodiment of the invention, the at least one clamping body is interrupted several times. A receiving space extending along a mounting plane may be opened in regular or irregular intervals by means of one or more cutouts in order to reduce the overall weight of the clamping body and therefore the leading flow body edge while still realizing a uniform mounting of the leading flow body edge on the flow body base body.
[0017] In an advantageous embodiment of the invention, the clamping body is realized in the form of a fold, the inner surfaces of which partially delimit the at least one receiving space. The clamping body therefore is an angled, plane component with a mounting link and a retaining surface that extends from the mounting link and on which the receiving space lies. In this context, a fold is a bend, an angular deflection or a bevel that essentially extends around the holding surface by 180°. A free end formed by the fold and the holding surface ideally do not contact one another, but rather are arranged at a distance from one another. The distance between the free end of the fold and the holding surface needs to be dimensioned such that the projection of the flow body base body can be inserted therein.
[0018] In an advantageous embodiment of the invention, the at least one projection comprises at least one opening that is dimensioned such that the at least one clamping body is slidable onto the at least one projection through the at least one opening. In this way, the installation of the leading flow body edge on the flow body base body can be significantly simplified because the sliding on or the insertion of the projection into the receiving space of the at least one clamping body does not necessarily have to take place over the entire length of the projection or the leading flow body edge, respectively. If the projection comprises one or more openings that are positioned such that they correspond to one or more clamping bodies, their cutouts, clear openings or the like, the leading flow body edge can be placed on the projection with a slight lateral offset such that the clamping body or clamping bodies lie in the openings of the projection in order to subsequently realize the attachment of the clamping body on the projection by means of a movement in or parallel to the plane of the projection.
[0019] In an advantageous embodiment, the at least one projection has the shape of a ramp in at least one region that is directed toward the at least one opening, wherein this ramp shape simplifies the attachment of the at least one clamping body on the at least one projection. In this context, the term ramp shape refers to the projection extending in a sloping fashion toward the openings.
[0020] In an advantageous embodiment of the invention, the at least one receiving space is tapered from an insertion width to a clamping width. In this case, a lateral sliding on can initially be realized with a low force that successively increases as the sliding progresses, for example, until the projection is clamped in the receiving space or the receiving spaces of the clamping body or the clamping bodies. In this case, the attachment of the leading flow body edge to the projection is significantly simplified.
[0021] In an advantageous embodiment of the invention, the rear end of the at least one second shell element comprises a tapered overlap in order to tightly fit against the first shell element. In this way, a flush surface and a harmonious transition from the second shell element to the first shell element are realized when the first end of the second shell element rests on the first shell element.
[0022] In an advantageous embodiment of the invention, the at least one second shell element is subjected to tension in a region between the at least one clamping element and the rear end when the at least one projection engages into the at least one receiving space, wherein said tension flushly clamps the rear end on the at least one first shell element. When the leading flow body edge is not installed, the second shell element may have a more significant curvature than specified, wherein this curvature leads to a slight contact pressure and therefore an always harmonious design of the transition when the first end of the second shell element is flushly placed on the first shell element.
[0023] In an advantageous embodiment of the invention, the width of the at least one receiving space is dimensioned such that the at least one projection adjoins at least two opposing boundary surfaces of the receiving space in a form-fitting fashion when the at least one projection engages into the at least one receiving space. In this way, the leading flow body edge is held in the specified position in a particularly simple and reliable fashion.
[0024] In an advantageous embodiment of the invention, the width of the at least one receiving space is dimensioned such that a bar body is insertable between the at least one projection and a boundary surface of the receiving space when the at least one projection engages into the at least one receiving space. In this embodiment, it is not necessary to laterally slide on the leading flow body edge to the flow body base body, wherein this provides particular advantages, for example, with very large leading wing edges, a large number of clamping bodies and a possibly non-linear extent of the projection. The leading flow body edge can be moved into a final position on the projection such that the projection is positioned in the clamping bodies. The intermediate space that still exists in the at least one receiving space can be filled with the bar body. It is particularly advantageous if the projection comprises connecting means, on which the bar body is held. These connecting means consist, for example, of holes, openings, bores or the like, through which rivets, screws, clamps or other elements can extend.
[0025] An advantageous embodiment of the invention furthermore comprises a tolerance compensation bar, wherein the depth of the receiving space of the at least one clamping body is greater than the extent of the part of the projection engaging into the at least one receiving space by a tolerance distance and the tolerance compensation bar bridges the tolerance distance when the at least one projection engages into the at least one receiving space. The tolerance compensation bar is inserted between the projection of the leading flow body edge and the receiving space of the clamping body such that manufacturing tolerances in the manufacture of the flow body base body and the leading flow body edge are compensated. For this reason, the receiving space should be dimensioned larger than required for the actual mounting function, i.e., realized with a greater depth. The desired dimension can be adjusted by inserting different tolerance compensation bars.
[0026] In an advantageous embodiment of the invention, the leading flow body edge and the flow body base body are realized with a divided rib structure with a leading flow body edge rib and a flow body base body rib that respectively comprise depressions in a connecting region, wherein said depressions form the clamping body in the assembled state of the divided rib structure. For example, the flow body base body rib and the leading flow body edge rib may respectively comprise, for example, a depression in the form of step-shaped recess, wherein the recesses face one another and jointly form the receiving space for accommodating the leading flow body edge in the assembled state of the two-part rib structure. Such a construction is particularly suitable for use in an aircraft wing. A second shell element can be connected to the leading flow body edge and may extend significantly beyond the location of the receiving space. The advantageous and above-described characteristics such as, e.g., the mounting, may be combined with this embodiment. The leading flow body edge rib and the flow body base body rib may comprise webs that serve for mounting the leading flow body edge rib and the flow body base body rib or the shell elements with the leading flow body edge rib and the flow body base body rib. The connection may be realized by means of bonding, riveting, welding or the like. A possible parting line advantageously begins at a connecting surface of the second shell element, from which the part of the second shell element lying above the flow body base body extends. When defining the position and the angle of such a parting line, the ease of access to the connection of the leading flow body edge rib and the flow body base body rib may be taken into consideration.
[0027] Another aspect of the invention is presented by an aircraft that comprises a flow body of the above-described type in the form of a wing, wherein the flow body base body is realized in the form of a wing box and the leading flow body edge is realized in the form of a leading wing edge.
BRIEF DESCRIPTION OF THE DRAWINGS
[0028] FIG. 1 shows a schematic representation of the flow body in the form of a simplified lateral section.
[0029] FIGS. 2 a , 2 b and 2 c show the mounting of the leading flow body edge on the flow body base body according to a first embodiment in the form of a simplified lateral section ( FIG. 2 a ), a simplified top view ( FIG. 2 b ) and a simplified three-dimensional representation ( FIG. 2 c ).
[0030] FIG. 3 shows a clamping body in the form of a simplified three-dimensional representation.
[0031] FIG. 4 shows a detail of a connection between the leading flow body edge and the flow body base body in the form of a simplified lateral section.
[0032] FIG. 5 shows a simplified lateral section through a leading wing edge and a wing box with a recess for a Krüger flap.
[0033] FIGS. 6 a to 6 c show the mounting of the leading flow body edge on the flow body base body according to a second embodiment in the form of a simplified lateral section ( FIG. 6 a ), a simplified top view ( FIG. 6 b ) and another simplified top view ( FIG. 6 c ).
[0034] FIG. 7 shows a detail of the connection between clamping body and angular deflection according to the second embodiment.
[0035] FIG. 8 shows an aircraft that is equipped with a flow body realized in the form of a wing.
DETAILED DESCRIPTION
[0036] FIG. 1 shows a flow body 2 that comprises a flow body base body 4 and a leading flow body edge 6 in the form of a somewhat simplified representation. The flow body base body comprises a first shell element 8 that forms a box-like object together with reinforcing components 10 . On a receiving end 12 , the first shell element 8 comprises a projection in the form of an angular deflection 14 with a shape that corresponds to that of a receiving space 16 of a clamping body 18 . The clamping body 18 is arranged on a second shell element 22 on an inner side 20 of the leading flow body edge 6 . It is particularly preferred to connect the clamping body 18 to the second shell element 22 by means of a welding seam 24 in order to limit the number of connecting means that extend outward. Alternatively, it would also be possible to choose bonded and laminated connections or different types of connections.
[0037] The peculiarity of the flow body 2 can be seen in that a very smooth and harmonious transition between the second shell element 22 and the first shell element 8 is realized in the receiving region 12 because practically no gaps or steps are created at this location and the laminarity of the flow around the flow body 2 is not impaired. Particularly significant advantages with respect to the aerodynamic performance are achieved, in particular, if the flow body 2 is used on an aircraft in the form of a wing with a flow body base body 4 that is realized in the form of a wing box and a leading flow body edge 6 that is realized in the form of a leading wing edge.
[0038] The leading flow body edge 6 is mounted on the flow body base body 4 as illustrated in FIGS. 2 a to 2 c that are described below. The leading flow body edge 6 is positioned relative to the flow body base body 4 in such a way that the receiving space 16 lies in a region of the angular deflection 14 of the flow body base body 4 . According to FIG. 2 b , the individual clamping bodies 18 can engage into openings 26 of the angular deflection 14 in order to be subsequently slid on the non-interrupted regions of the angular deflection 14 . FIG. 2 b shows the final position of two clamping bodies 18 that are arranged on the second shell element 22 . The illustration in FIG. 2 b only shows a section of the leading flow body edge 6 and the angular deflection 18 or the first shell element 8 , respectively, but it goes without saying that further clamping bodies 18 may be provided.
[0039] FIG. 2 c shows a three-dimensional representation of the angular deflection 14 and a cutout 26 , into which a clamping body 18 can engage in order to be subsequently displaced toward the left in the plane of projection. In order to simplify the sliding on, the angular deflection 14 may be shaped like a ramp 28 in a region near the cutout 26 , wherein this ramp is characterized by an edge angle α referred to the axis 30 , along which the angular deflection 14 extends.
[0040] FIG. 3 shows an advantageous design of the clamping body 18 that further simplifies the attachment. In this case, the clamping body 18 is realized in the form of a sheet metal-like angle with a fold 32 , the width of which is tapered from a width b 2 on an insertion end 34 to a width b 1 on a retaining end 36 . For example, the height of the receiving space may also be reduced from a height h 2 on the insertion end 34 to a height h 1 on the retaining end 36 .
[0041] FIG. 4 shows a detail of an angular deflection 14 and a clamping body 18 for a first embodiment. According to this illustration, the first shell element 8 is shaped such that a lowered receiving surface 38 for receiving the second shell element 22 is provided. The second shell element 22 comprises a tapered overlap (mounting) or has a tapered thickness in order to realize the transition to the first shell element 8 as flush as possible. In order to further improve the durability of the harmonious transition, a rear end 40 of the second shell element 22 may be positioned such that the curvature of the second shell element 22 in the region between the end 40 and the position of the clamping body 18 is more significant in the non-mounted state than in the mounted state. In this way, a pre-tension is realized that continuously presses the second shell element 22 on the first shell element 8 .
[0042] FIG. 5 shows a leading flow body edge 42 and a flow body base body 44 that are designed for use on an aircraft wing. In this case, the clamping body is realized in the form of a two-part rib structure with a leading flow body edge rib 46 and a flow body base body rib 48 that respectively comprise a depression 49 , 51 such as, e.g., a respective step-like recess, wherein said depressions face one another and jointly form a receiving space 54 inserting an angular deflection 52 of the first shell element 54 in the assembled state of the two-part rib structure. A second shell element 56 is connected to the leading flow body edge rib 46 , for example, by means of bonding or welding and extends significantly beyond the location of the receiving space 50 , wherein this second shell element comprises a tapered overlap and forms a very harmonious transition to the first shell element 54 . An internal riveting to rib bases or the like may also be purposeful. In the bonded variation, it is proposed to realize a riveting to the second shell element 56 on the underside. The front rib section is preferably preassembled with the second shell component 56 . The rear flow body base body rib 28 on the wing side is preassembled with the first shell element 54 and may comprise internal riveted connections and/or bonded or welded connections. After assembling the leading flow body edge 42 and the flow body base body 44 and clamping together the two components, the leading flow body edge rib 46 and the flow body base body rib can be riveted to one another. Alternatively, it would also be conceivable to use a screw connection that may possibly be combined with shear pins.
[0043] A possible parting line advantageously begins at a connecting surface of the second shell element 56 , from which the part of the second shell element 56 lying above the flow body base body 44 extends. When defining the position and the angle of such a parting line, the ease of access to the connection of the leading flow body edge rib 46 and the flow body base body rib 48 may be taken into consideration. Bottom chords of the leading flow body edge rib 46 and the flow body base body rib 48 can be advantageously connected by means of a connecting link or a doubler. Due to this architecture, the leading flow body edge 42 may be realized in the form of a preassembled subcomponent. Consequently, the observation of the tolerance with respect to the position of the kinematic load application points is also simplified.
[0044] A larger recess 58 illustrated on the underside of the leading flow body edge 42 and the flow body base body 44 serves for receiving a Krüger flap.
[0045] FIGS. 6 a to 6 c show a design that is modified in comparison with FIGS. 2 a and 2 b , wherein a leading flow body edge 6 with clamping bodies 18 is placed on an angular deflection 14 in order to be subsequently fixed by means of bar bodies 60 that are respectively introduced or inserted into the receiving spaces 16 of the clamping bodies 18 .
[0046] FIG. 7 shows a somewhat more detailed illustration, in which the receiving space 16 of the clamping body 18 is dimensioned slightly larger than in the first exemplary embodiment such that the bar body 60 can also be introduced in addition to the angular deflection 14 . In order to further compensate manufacturing tolerances, the receiving space 16 extends over a larger region than necessary, wherein the empty excess space is filled with a tolerance compensation bar 62 .
[0047] FIG. 8 ultimately shows a highly schematic representation of an aircraft 64 with two wings 66 that respectively comprise a wing box 68 and a leading wing edge 70 , wherein the wing box represents the flow body base body. Due to the advantageous inventive design of the connection between the wing boxes and the leading wing edges, the influence on the laminarity of the aerodynamic flow can be reduced such that the aerodynamic performance can be increased and the number of components required within the wings 66 for connecting leading flow body edges 70 is simultaneously reduced.
[0048] As a supplement, it should be noted that “comprising” does not exclude any other elements or steps, and that “a” or “an” does not exclude a plurality. It should furthermore be noted that characteristics described with reference to one of the above exemplary embodiments can also be used in combination with other characteristics of other above-described exemplary embodiments. Reference symbols in the claims should not be interpreted in a restrictive sense. | A flow body includes a flow body base body with a first shell element, a leading flow body edge with a second shell element and a clamping body, and a receiving space partially delimited by the clamping body. The flow body base body includes on a front end a projection, having a shape corresponding to that of the receiving space for engaging into the receiving space. The clamping body is internally arranged on the leading flow body edge spaced apart from a rear end of the second shell element. The rear end of the second shell element is flushly positioned on the first shell element when the projection engages into the receiving space. A smooth and harmonious transition that does not influence a laminar flow around the flow body can be achieved between the two components. | 1 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
Embodiments of the present invention relate to devices and methods aiding in movement of people and objects in general including but not limited to a dolly, a cart, a fork lift, a hand truck, a roller skate and the like.
2. Related Art
Various devices for aiding in movement of people and objects along a surface have been proposed, in which rotatable wheels are attached to a structural body. When a force is applied in the desired direction of movement, the wheels rotate along the surface and decrease friction between the structural body and the surface.
Various different mechanisms and methods have been used for applying such a force, including a motor that connects, through a transmission or other linkage to one or more wheels, to impart a rotational force to the connected wheels. Other mechanisms have employed a rotary pedal configuration in which foot pedals are attached to a rotary sprocket and a chain or belt connects the sprocket to a wheel gear.
Wheel motion on such apparatuses is usually limited to rotational motion about an axis of rotation. However, wheels on a roller skate or in-line skate are moved up and down (relative to the riding surface), as the rider's legs are lifted and set down, to impart a motive force in a generally horizontal direction of travel. As a result of the up and down motion of the wheels during a skating motion, much force is exerted in a perpendicular direction to the movement of the apparatus, resulting in a considerable amount of wasted energy.
Previous inventions have attempted to remedy the problem, but either required complicated designs or required alteration of the conventional style of use of the device. Examples of previous designs are described in U.S. Pat. Nos. 1,208,173; 732,120; 1,924,948; 1,437,314; and, 1,784,761, each of which are incorporated herein by reference, in its entirety.
SUMMARY OF THE DISCLOSURE
Embodiments of the current invention may be configured to address one or more of the above-mentioned problems, including providing a system and method for converting a perpendicular force to a rotational force and utilizing the rotational force to propel the system in the desired direction. Further embodiments of the invention relate to a method of manufacturing such a system.
More particularly, a system according to a first preferred embodiment converts a force applied to the system in one direction to a rotational force to drive the system in a second direction. The system in this embodiment comprises a pressure part, a motive force transfer mechanism engaged with the pressure part and moveable between at least two states, a spin restricting mechanism with at least two parts that move with respect to each other, and a bias member that provides a bias force. The motive force transfer mechanism has a resting state, wherein no external forces are acting on the system, and an active state, wherein an external force is acting on the pressure part. The motive transfer mechanism is coupled to the system along a single axis allowing it to pivot freely along that axis with respect to the pressure part and to compress in a scissor-like fashion. The motive transfer mechanism engages with a first part of the spin restricting mechanism when transitioning between the resting state and the active state. The bias member causes the motive transfer mechanism to transition back to the resting state when no external force is applied to the system.
The spin restricting mechanism has a first part and a second part that rotate independently along a shared axis in one direction, and are coupled and rotate together in the opposite direction. As a result, the system may provide a rotational force in two directions to the first part, but will only transfer a rotational force in one direction to the second part. Accordingly, the system may be driven in one direction, such as a forward direction.
A system in a second preferred embodiment comprises a system of the first embodiment, but with a plurality of wheels and each wheel is attached to a second part of a spin restricting mechanism. Each spin restricting mechanism is engaged to the motive force transfer mechanism. This provides an advantageous results that the system may move along a surface in a given direction from a force provided perpendicular to the surface.
A system in a third preferred embodiment comprises a system of the first embodiment, but with a plurality of wheels and at least one wheel attached to a second part of a spin restricting mechanism. This provides an advantageous result that the system may move along a surface in a given direction from a force provided perpendicular to the surface.
A system in a fourth preferred embodiment comprises a system of the first embodiment, but wherein the first part and second part of the spin rotation mechanism have locking elements that lock into each other when rotating in one direction, but slide against each other freely when rotating in the opposite direction. These locking elements may comprise a first plate with wedges in the shape of ramps, and a second plate with slots or holes that are shaped to receive the wedges.
A system in a fifth preferred embodiment comprises a system of the third embodiment, but wherein the pressure part comprises a shoe attached to the motive transfer function.
A system in a sixth preferred embodiment comprises a system of the third embodiment, but wherein the pressure part comprises a platform on which a user may step.
A system in a seventh preferred embodiment comprises a system of the sixth embodiment, but with a member (for example straps) to secure the user's foot, shoe, or the like to the system.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an external side view of a motive system according to an embodiment of the invention in its original uncompressed form.
FIG. 2 is an external side view of the motive system of FIG. 1 in its compressed form.
FIG. 3 is an internal side view of the motive system of FIG. 1 with the housing removed.
FIG. 4 is a close-up view of a drive train mechanism according to an embodiment of the invention.
FIG. 5 is a close-up view of a drive train mechanism according to another embodiment of the invention.
FIG. 6 . is an exploded view of an embodiment of a spin restricting mechanism.
FIG. 7 . is a top internal view of an embodiment of a spin restricting mechanism where wedges on a circular plate are locked into a spinning slotted plate.
FIG. 8 . is a top internal view of an embodiment of a spin restricting mechanism where wedges on a circular plate are sliding along a spinning slotted plate.
FIG. 9 is a close-up view of a drive train mechanism according to a further embodiment of the invention.
FIG. 10 is an external side view of a motive system according to a further embodiment of the invention in its original uncompressed form.
FIG. 11 is an internal side view of the motive system of FIG. 10 with the housing removed.
FIG. 12 is a perspective view of the motive system of FIGS. 1-3 , in its compressed form.
FIG. 13 is an external side view of a motive system according to an embodiment of the invention in its original uncompressed form.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
Embodiments of the present invention relate to motive systems and methods aiding in movement of people and objects in general including but not limited to a skate, a dolly, a cart, a fork lift, a hand truck, and the like, and components thereof. In addition, embodiments of the invention relate to motive systems and methods for converting a force (such as, but not limited to, a perpendicular or generally perpendicular force) to a rotational force. Motive systems and methods according to embodiments of the present invention include (1) a scissoring motive transfer mechanism and a drive train linkage that converts force applied in one direction (such as a vertical, downward force applied by a user making a stepping motion) into a rotational force for driving one or more rotary wheels; and (2) a spin restricting mechanism for restricting the rotary wheel(s) to only one direction of rotation.
A motive system according to an embodiment of the present invention is shown in FIGS. 1-3 and 12 , in various positional states. FIG. 1 is an external side view of system structure in an uncompressed or resting state. FIG. 2 is an external side view of the system of FIG. 1 , but in a compressed or active state. The exterior of the system, as shown in FIGS. 1 and 2 , is provided with a pressure part 1 , a scissoring motive transfer mechanism 2 , a drive train 5 , wheels 7 , and a chassis 16 . FIG. 12 is a perspective top-side view of the system structure in the compressed or active state, with the pressure part 1 omitted to provide a clearer view of various components within the motive system.
FIG. 3 is an internal side view of the embodiment of the system of FIG. 1 . The interior of the system, as shown in FIG. 3 , is provided with a bias member 8 , a rod or bar 3 supported for pivotal motion about its longitudinal axis, a drive train 5 , and a spin restricting mechanism (not shown in FIG. 3 but illustrated in FIGS. 6-8 ).
The system of FIGS. 1-3 and 12 may be employed, for example, in a skate structure for allowing a user to skate along a surface. A skate structure according to embodiments of the present invention may be secured directly to each foot of a user. Alternatively, the skate structure may be incorporated with a skate shoe, in a manner similar to a traditional roller skate (see for example, shoe 30 of FIG. 13 ). In other embodiments, the skate structure may be employed in another form of a motive system, including but not limited to a dolly, a cart, a fork lift, a hand truck, and the like.
According to an example embodiment shown in FIG. 1 , the pressure part 1 comprises a stepping plate that may be part of the chassis 16 . The stepping plate may provide a generally planar surface on which the sole of a users shoe or foot may impart a generally downward-directed manual force, while making a stepping motion. In other embodiments, the pressure part 1 may comprise the sole of a shoe structure for receiving a user's foot. However, other embodiments of the pressure part may include, but are not limited to, a platform, foot rail or a hand rail, on which manual force is applied by a user's foot or hand. In one embodiment according to FIG. 1 the chassis 16 may be directly attached to a shoe structure by a series of fastening elements (for example screws) that extend through mounting holes 9 into, for example, the sole of a shoe structure. In other embodiments, other suitable structure for securing the chassis 16 to a user's foot or to a shoe structure may be employed, including, but not limited to straps, adhesive material, or the like. The chassis 16 may be connected to the motive transfer mechanism 2 at a single axis, by a pivoting rod or bar 3 . The pivoting rod or bar 3 can be a screw, a bolt, a rod, or a ball-bearing device, and the like. In this embodiment, the pivoting rod or bar 3 is not stationary relative to the chassis 16 or motive transfer mechanism 2 , and may rotate freely relative to either structure. In alternative embodiments, the rod or bar 3 may be non-rotating and provide a fixed axle about which the chassis 16 and motive transfer mechanism 2 may pivot in a rotary manner.
In an embodiment according to FIG. 1 the motive force transfer mechanism 2 has a scissor-like shape made of two arms connected at a pivot axis by the pivotal rod or bar 3 , as shown in FIG. 3 . The arms may be made of any suitably rigid material, including, but not limited to metal, plastic, composite material or the like. The arms are pivotal about the pivot axis, between a first final state (which may be a resting state or uncompressed state) as shown in FIG. 1 , and a second final state (which may be a compressed state) as shown in FIG. 2 . The bias member 8 may comprise a coil spring that imparts a spring force on the two metal arms. In the illustrated embodiment, the bias member comprises a coil spring having a first spring arm connected in a fixed relation with one of the two scissor arms and a second spring arm connected in a fixed relation to the other of the two scissor arms and a coil arranged around the pivot axis of the scissor arms, for biasing the scissor arms toward the first final state (as shown in FIG. 1 ). However, in other embodiments, the bias member 8 may comprise a leaf spring or pneumatics. The arms may rotate with respect to each other and with respect to the pressure part 1 around the axis of the pivoting bar 3 . This may provide the advantageous result that pressure may be applied to the pressure part 1 in whatever foot angle position (foot angle, relative to the direction of a downward stepping motion) is most natural or comfortable for each user while still engaging the motive transfer mechanism 2 .
When no external force is applied to the motive force transfer mechanism 2 , the bias member 8 applies a force to the metal arms so they are in an uncompressed position as shown in FIG. 1 .
When a sufficient external force to overcome the force of the bias member 8 (such as, but not limited to, a force from a user's foot as the user makes a downward stepping motion) is applied to the pressure part 1 while the motive transfer mechanism 2 is supported on a surface of travel, the bias member 8 compresses and the arms rotate into a compressed state as shown in FIG. 2 .
According to an embodiment of the system of FIGS. 1-3 , a series of teeth 2 A are provided along the end of at least one of the metal arms, for engaging a first gear 5 A of the drive train 5 . The series of teeth 2 A are shaped to engage with a first, smaller ring of teeth on the gear 5 A as shown in FIG. 4 . Gear 5 A also has a second, larger ring that rotates on the same axis and together with the smaller ring of teeth.
According to the embodiment of a drive train 5 in FIG. 4 , a larger ring of gear 5 A may have teeth and may be engaged with teeth of a second gear 5 B of the drive train 5 , which in turn may be engaged with teeth of a third gear 10 , which according to the embodiment of FIG. 4 may be attached to the spin restricting mechanism for rotation with a portion of the spin restricting mechanism.
According to another embodiment shown in FIG. 5 , the larger ring on gear 5 A may have teeth and may be connected to a gear 10 through the use of a chain 20 . In yet a further embodiment as shown in FIG. 9 , each of the larger ring on the gear 5 A and the gear 10 may comprise a pulley 22 and 24 and the two pulleys may be coupled by a belt 20 instead of the chain 20 shown in FIG. 5 . Accordingly, a chain or belt may transfer rotational motion between the gear 5 A and the gear 10 .
The drive train 5 provides an operable link between the scissoring arm structure and the gear 10 , to provide a rotational drive force to rotate gear 10 . More specifically, the drive train transfers a rotational force for rotating the gear 10 in a first direction around the axis of gear 10 , as the scissoring arm structure is moved from the uncompressed or rest state ( FIG. 1 ) to the compressed or active state ( FIG. 2 ). The drive train transfers a rotational force for rotating the gear 10 in a second direction around the axis of the gear 10 (opposite to the first direction), as the scissoring arm structure is returned from the compressed or active state ( FIG. 2 ) to the uncompressed or rest state ( FIG. 1 ).
However, the spin restricting mechanism is operatively coupled to the gear 10 , to transfer the rotational motion of the gear 10 in the first direction to a wheel, but not transfer rotational motion of the gear 10 in the second direction to the wheel. Accordingly, a rotational motive force may be applied to the wheel in a desired direction of motion.
FIG. 6 shows an exploded view of an embodiment of a spin restricting mechanism. According to an example of this embodiment one part of a spin restricting mechanism comprises a circular plate 12 coupled in a fixed relation to a wheel hub 14 . The wheel hub 14 is supported for rotation about an axis of an axle. The wheel hub axle is connected to one end portion of one of the scissor arms. A second part of a spin restricting mechanism comprises a slotted plate 11 coupled in a fixed relation to the gear 10 , to rotate with the gear 10 . A wheel 7 may be coupled in a fixed relation to the wheel hub 14 , to rotate with the wheel hub. The plates 11 and 12 and the wheel hub 14 , each may be formed of any suitably rigid material, including, but not limited to metal, plastic, composite material or the like.
The wheel hub 14 may be provided with a plurality of spring receptacles and pin receptacles arranged in a spaced relation, around the rotational axis of the wheel hub 14 . The spring receptacles may comprise channels or other structures that are capable of receiving and/or retaining springs. The pin receptacles may comprise channels or other structures that are capable of receiving and/or retaining pins.
A plurality of springs 13 , such as coil springs having longitudinal axes, may be received, at least partially within the spring receptacles, such that an end portion of the spring is extends outward from the hub 14 . A plurality of pins 15 having longitudinal axes may be received partially within the pin receptacles, such that an end portion of each pin extends outward from the hub 14 , in a direction generally parallel to the rotational axis of the hub. The circular plate 12 may be coupled in a fixed relation to the wheel hub 14 by arranging the outward extended ends of the pins 15 to extend through holes in the circular plate 12 . Accordingly the circular plate 12 and wheel hub 14 rotate together along a common axis. The outward extended ends of the springs 13 are positioned to abut or otherwise impart a spring force on the circular plate 12 . The circular plate 12 may have some freedom of movement in the axial direction (of the axis of rotation), which causes springs 13 to compress and decompress accordingly. The slotted plate 11 , which may also have a circular shape, is arranged adjacent the circular plate 12 , opposite to the spring-side of the plate 12 , such that the springs 13 impart a force on the plate 12 to push the plate 12 against the slotted plate 11 .
According to an embodiment of the spin restricting mechanism as shown in FIG. 6 , the circular plate 12 may have wedge-shaped portions on the surface facing away from the wheel hub 14 . Each wedge-shaped portion may be configured to form a ramp-like shape as shown in FIG. 7 . Each wedge-shaped portion may have a ramp side 12 B that starts flush with a plate surface of the plate 12 , and rises at an angle less than 90 degrees. The wedge then forms a relatively sharp drop to the plate surface, forming an edge 12 A that is approximately perpendicular (or greater than 90 degrees) to the plate surface. The wedges may all be aligned so the ramps face the same rotational direction. The slots on the slotted plate 11 may be about the same size as or larger than the wedges on the circular plate 12 .
FIG. 7 shows an internal top view of an embodiment of a spin restricting mechanism according to FIG. 6 . In this embodiment, when the slotted plate 11 is rotated in the direction so that the edge of the slots slide down the ramp side 12 B of one wedge and hit the edge 12 A of another wedge, the circular plate 12 locks into the slotted plate 11 and may be held in place by the force from the springs 13 . When locked, rotation of the slotted plate 11 in a first direction around the axis of the hub 14 transfers, through the edges 12 A of the wedges, to plate 12 to cause rotation of the plate 12 , wheel hub 14 and wheel 7 .
FIG. 8 shows an internal top view of an embodiment of a spin restricting mechanism according to FIG. 6 . In this embodiment, when the slotted plate 11 is rotated in a second direction (opposite to the first direction of rotation) so that the edge of the slots slide up the ramp side 12 B of each wedge and then falls back to the surface, the circular plate 12 is not locked for rotation with the slotted plate 11 and the slotted plate 11 may rotate in a second direction (opposite to the first direction) independently of the circular plate 12 . The springs 13 compress and decompress as the slotted plate 11 moves up and down the ramps.
Embodiments of FIG. 6 of the spin restricting mechanism 6 provide an advantageous result that the wheel only spins in one direction and only receives a force from the slotted plate 11 in one rotational direction. Accordingly, the skate will only be propelled forward when the motive force transfer mechanism 2 is moved from an uncompressed or rest state ( FIG. 1 ) to a compressed or active state ( FIG. 2 ) and may continue spinning in that direction when the motive force transfer mechanism 2 returns from the active state ( FIG. 2 ) to the rest state ( FIG. 1 ) and decompresses.
An embodiment of the invention according to FIGS. 1-8 may function so that when a user steps down on the pressure plate 1 , the wheels 7 come in contact with a surface of travel, such as the ground, the force of the user's body weight along with the counteracting force from the surface of travel cause the motive transfer mechanism 2 to move from an uncompressed or rest state ( FIG. 1 ) to a compressed or active state ( FIG. 2 ). As the metal arm with the teeth 2 A moves during the compression, the movement causes the gear 5 A engaged with the teeth 2 A to rotate. The rotation of the gear 5 A is transferred to gear 10 , for example, through a further gear 5 B chain, belt or the like.
The slotted plate 11 is coupled to rotate with gear 10 and the edge of the slots rotates along the circular plate 12 until they engage an edge 1 2 A, causing the circular plate to rotate with the slotted plate. The wheel hub 14 and wheel 7 are coupled, in a fixed relation to the circular plate 12 , through the pins 15 and, thus, rotate with the rotation of the circular plate 12 . Accordingly, the energy of the vertical motion of the pressure plate 1 and the compression of the scissor arm structure is transferred to a rotational motion of the wheel 7 , for propelling the user forward.
When the user steps back up, the compression force is released and the wheels may be lifted off of the ground. As a result, the bias member 8 forces the arms back into the decompressed or rest state ( FIG. 1 ). The gear 10 is rotated again by the movement of toothed arm, but in the opposite direction relative to the direction of rotation during a compression step. The slotted plate 11 is coupled in a fixed relation to the gear 10 and, thus, rotates with gear 10 . As the slotted plate rotates, the edges of each slot rotate along a circular plate 12 moving up and down the ramp portions 12 B so as to allow the wheels 7 and circular plate 12 to continue rotating in the forward direction. To allow the ramp portions to readily slide along the plate 12 , the circular plate 12 may move along the axis of rotation from a force from the slotted plate 11 , against or with the spring force of springs 13 .
Accordingly, in this embodiment, the user may repeat the stepping motions to continue propelling the skate and the user forward.
FIG. 10 & 11 illustrate a further embodiment of a motive system that engages more than one wheel. FIG. 10 is an external side view of the motive system in its original uncompressed form, and FIG. 11 is an internal side view of the motive system of FIG. 10 . Similar to the motive system of FIG. 1 , the motive system of FIGS. 10-11 comprises a pressure part 1 , a scissoring motive transfer mechanism 2 , a pivotal rod or bar 3 , wheels 7 and 7 ′, and a bias member 8 . As illustrated in FIG. 11 , each of the end of the two arms of the scissoring motive transfer mechanism 2 comprises a series of teeth 2 A and 2 A′. Each series of teeth 2 A and 2 A′ engages with one of drive mechanisms 5 and 5 ′, respectively. In turn, each of the drive mechanisms 5 and 5 ′ engages with one of gear 10 (connected to wheel 7 ) or gear 10 ′ (connected to wheel 7 ′). Each of the wheels 7 and 7 ′ also comprises a spin restricting mechanism (not shown in FIGS. 10-11 , but illustrated in FIG. 6 .) Therefore, this provides the advantageous result that as a downwards force is applied to the pressure part 1 , the downwards force is transferred and distributed to rotational motions of both wheels 7 and 7 ′, for propelling the user forward.
Further, the gears of the two drive mechanisms 5 and 5 ′ may comprise a different number of gears or different gear ratios. For example, as illustrated in FIG. 11 , the drive mechanism 5 comprises a set of two gears 5 A and 5 B, whereas the drive mechanism 5 ′ comprises only one gear 5 ′. Therefore, by varying the number of gears or gear ratios between the two drive mechanisms 5 and 5 ′, the proportional fraction of force transferred to the two wheels 7 and 7 ′ can be adjusted.
An explanation of the present invention was given above of the present invention based on several preferred embodiments. However, the present invention is in no way limited to the preferred embodiments described above. Various modifications and changes that do not deviate from and are within the scope of the essentials of the present invention can be easily surmised. | A mechanism for the conversion of a force applied in one direction to a rotational force. The rotational force may provide for movement in a second direction. The system utilizes mechanical parts and the movement of these parts to convert the directional force to a rotational force. The system can help to utilize unused forces to the benefit of a user reducing workload and/or increasing speed. | 0 |
This is a Continuation-in-Part Application for No. 09/166,471 filed Oct. 5, 1998, which is now requested to be abandoned. This CIP incorporates the two preliminary amendments to the parent application. They were filed Dec. 29 and 31, 1998. Other new material, in addition to that of the preliminary amendments, is included.
SUMMARY OF THE INVENTION
This is the invention of a cruise control adaptation for trucks to improve their delivery performance. Such performance for a truck is derived from its speed of delivery and its fuel mileage. The performance is optimized by this invention in automatically making the appropriate cruise control throttle setting changes as road slope changes. An increase in slope (going into a climb) results in a prompt fuel rate increase. With a decrease in positive slope, approaching the crest of a hill, speed stays constant, i.e., fuel decrease. With progressing negative slope requires there is fuel decrease even below set speed. Throttle settings arranged simply for maximum fuel mileage can sacrifice speed too much for good delivery performance.
The economic factors of speed and fuel mileage come into play especially in a large part of the U.S. where trucks encounter roads with consistently undulating hills. For hill climbing this invention operates under cruise control to maintain speed at the transition from level control to climbing. It also saves fuel (1) in downhill travel (2) in travel with variable winds (3) in slope changes from climbing to descending (4) in various road slope changes during a climb (5) in the changing from climbing to level transit, and (6) in acceleration from stop or slow speed to cruise speed.
The optimum truck speed for best fuel mileage in hill climbing can be too slow for best overall motor freight economics because a trip shortened in time by speed obviously has economic advantages. If fuel consumption were the only consideration in truck speed, trucks would travel at forty miles per hour and would climb hills in the fashion of the Japanese patent 8-295154.
This invention addresses both economic factors, speed and fuel consumption. In this regard it works better than the conventional speed control which has no fuel conserving features involving road slope changes and the Japanese approach which operates during uphill travel only for fuel conservation.
There are at least three distinctly different types of cruise control for vehicles including this invention. First, the most common (state-of-the-art or "SOA") is in use with many vehicles of the road. The SOA cruise control adjusts the engine power to hold a set speed as the vehicle goes through various road slopes. It makes no attempt to anticipate a hill climb; in fact, it has a delay in responding to the increased fuel demand of a hill. Another cruise control is described in Japanese patent 9-295154. It reduces the speed to allow a vehicle to climb a given hill with minimum use of fuel. The hill climb can be quite slow at the speed of best fuel economy. The third type, this invention, operates to hold speed as a hill is begun. It does not interfere with the driver's goal of speedy delivery, while it provides a degree of fuel conservation. It does this in the transition of slope as a hill is entered. Also, the system of the invention operates differently from that of the Japanese in downhill travel. The present system allows a degree of speed droop in descending by keeping the fuel flow stopped if the hill is steep enough. The Japanese concept operates to maintain the set speed or a higher speed using automatic braking
The controller of Japanese patent 8-295154 uses measurement of road slope ahead to define the hill being climbed by the truck. The following aspects of the Japanese patent are different from our concept: (1) a goal of minimum fuel usage in the climb of a hill and (2) the use of the truck power train operating characteristics in combination with the road slope to determine the speed of climb on the hill and (3) measurement of the road slope ahead of the truck. It does not respond to the positive transition of slope at the beginning of a hill in the manner of our invention. In fact, the Japanese concept reduces speed as soon as it detects an increased slope ahead. Immediately, it changes the speed toward a lower value to be held during the climb.
The technique of this invention for hill climbing begins at the very start of the hill. Slope is measured at the truck, not ahead. Power is advanced the moment the slope increases. The SOA cruise control systems normally have a built in lag of about 200 engine revolutions. This is too long for a good start on a hill. Consequently, there tends to be a speed droop as the truck goes into a climb. Actually, a surge in power is the better procedure as the hill is entered. The present invention supplies that. If the climb gets steeper, the control will respond sooner than that of an SOA control in calling for more fuel flow. As the crest of the hill is approached with declining slope, the climb having been steep enough that set speed could not be held, the present control will hold off speed increase through the crest of the hill and on until the slope stops decreasing when set speed will be resumed.
If a downhill is steep enough to allow adequate speed with fuel flow off, this allows fuel conservation. With an SOA cruise control, as a truck proceeds downhill on a slope where set speed cannot be reached without fuel, the controller will call for fuel. This invention allows a pre-determined speed droop of 5 mph, for example, before fuel is called for. This opens up opportunities for fuel to be saved without a great sacrifice in speed.
This invention can be set to preclude a fuel flow change when the slope data indicates no slope change, yet a speed change occurs, i.e., the change in speed is caused by a wind speed change. At the same time, the controller is quick to respond to a slope change in synchronization with whatever the changing road slope is. Any tendency for the controller to call for excessive power when an increase in slope is detected, can be avoided by the programming of the reaction to the slope change.
The present invention uses computer-type programming to allow fuel flow, under a given target speed, to be changed with the changing of road slopes in Hilly Country. An optimum balance between fuel economy and good speed is programmed. A cruise control designed for maximum fuel mileage, only, on a hill climb, such as the Japanese patent, would not result in optimum economics for the motor freight mission.
The slope measured by a dangleometer or other type of sensor of road slope can be adjusted by acceleration data input for the effect of acceleration on the perceived slope. The acceleration sensor could be of the inertial type or the signal could be derived from the monitoring portion of an automatic braking system or it could be derived from the part of an SOA controller which monitors speed and its changes.
There is a maximum RPM for each engine above which fuel mileage becomes especially degraded. Therefore, among the features of control under this invention to be programmed, a limit on engine RPM can be included, especially in acceleration to cruise speed.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a diagram of a system in which the conventional cruise control signal for fuel flow is modified by a measurement of road slope change after it is adjusted for acceleration's effect on slope measurement.
FIG. 2 is a diagram of a system much like that of FIG. 1, except with a different arrangement of the data input and with engine RPM an added input. Also, acceleration, itself, is used as a factor in the control's establishment of fuel flow rate. Actually, acceleration is directly or indirectly accounted for in every case.
FIG. 3 is a diagram of a system in which the conventional cruise control signal for fuel flow is modified in one central computation involving acceleration, slope and engine RPM.
FIG. 4 is a diagram of a system with even more of a centralized computer unit that processes inputs to adjust the SOA fuel signal.
FIG. 5 is a diagram illustrating the case of having the slope measurement alter the fuel flow signal from an SOA cruise control unit.
FIG. 6 is a diagram illustrating the most straightforward case of having the slope measurement alter the set speed on an SOA cruise control unit.
DETAILED DESCRIPTION
In FIG. 1 automatic cruise control 1 is turned on at 3 and instant speed becomes the speed setting. There is a conventional "increase speed" button 27. A conventional cruise control computer 25 develops a signal for fuel flow rate 2. This is one of many possible arrangements for using slope measurement and its change 4 to adjust the cruise control signal 18 to the fuel flow 2. The slope sensor, itself 4, or the software processing its signal within 20 would be dampened to discount jiggling due to bumps in the road. Acceleration, computed at 25 from the rate of change of speed, is imposed at 20 on the slope to adjust for the effect of acceleration on perceived slope. Both the slope change from 20 and the fuel setting from 25 combine at 18 to determine the fuel signal that is then transmitted to the fuel flow controller 2. As in SOA controls, there is a foot feed 9 always available to the driver to control fuel feed over the computer control. Acceleration measurement is a part of most speed controllers because the controller looks at rate of approach (rate of speed change) to the set speed in developing its fuel flow signal. This controller has the conventional "increase speed" button 27 and the "controller off" 28 activated by the brake pedal.
Slope change alone in this invention can control a change in fuel flow. However, the relationship of slope to fuel flow requirement is complicated by concomitant changes in rolling friction and wind friction. Nevertheless, the embodiment of FIG. 1 would utilize only slope as a new input to cruise control.
In FIG. 2 another version of the control is shown in which RPM 7 can have an effect on the fuel flow signal. Acceleration also is used in the fuel flow calculation of the controller. In the diagram, acceleration 6 is shown apart from the speed set/speed sensing 8 comparison of the computer because it is a separate acceleration sensor such as a liner accelerometer mounted on the frame of the truck. The computer 1 uses the measurement of speed 5 and the speed setting 3 to develop a signal of fuel demand at 8. It then modifies that signal at 11 based on the measurement of acceleration 6. Again, the fuel flow signal is modified at 12 based on the measurement of changing slope 14. The primary measurement of changing slope 4 is corrected at 14 for the effect of acceleration on the slope measurement. The RPM sensor 7 is programmed to reduce the fuel signal developed at 12 if a pre-set RPM limit is otherwise exceeded. Finally at 10 a signal is sent to the fuel feed regulator 2. Driver override by foot feed 9 can determine fuel flow. Slope change is the major element affecting a change in fuel rate by the controller, although speed differential, actual Vs setting, is always a factor, too. The controller also has an "increase speed" button 27 and an "off" signal 28 with the brake pedal. The fuel signal from 10 also goes back to 11 in order that acceleration due to fuel flow change can be accounted for.
In FIG. 3 the speed setting 3 is modified by the computer 17 based on acceleration and changing slope measurements. The modified signal from the processor 15 is combined with speed 5 to develop at 16 the signal for fuel flow. The speed 5 and signal from processor 15 combine much like in a conventional cruise control. The acceleration that is beyond what the instant fuel flow is causing could be caused by wind. Therefore, fuel flow rate is fed back 22 to the computer's calculations which use the acceleration measurement. The acceleration measurement 6 can be separate from the controllers 17 or it can come from the computer's reading of change in speed. In this diagram it is shown as a separate measurement.
In FIG. 4 the modification of the cruise control signal 8 takes place in one central processor 9 within the computer 1. At 9 is generated the fuel signal 10, based upon the measurements of acceleration 6, slope 4, speed 5, RPM 7 and fuel flow signal 22.
FIG. 5 shows an SOA cruise controller 30; a slope change signal 33 leading from a measurement of slope change 34; the signal adjust 32 where speed setting 3, speed data 5, and fuel signal 31 from the SOA controller 30 are used to create an adjusted fuel rate signal 28 which leads to the fuel pumping system 35. The signal adjust 32 is programmed based on road testing development to optimize its performance. Through road testing the algorithms and constants used in programming are derived to produce fuel saving results and to provide against excessive fuel rate changes as the slope changes. This makes signal adjust 32 operate like an expert driver who gets superior fuel mileage.
FIG. 6 shows an SOA cruise controller 30; a changing slope measurement signal 33, leading from a slope measurer 34, and the speed set 3 leading to the speed set adjust 36 where the normal speed set 3 for the cruise controller 30 is adjusted for the effect of slope change. The rationale 29 of speed set adjust is based upon algorithms founded with road testing and evolved with self-teaching 37 to result in an optimum set speed adjust rationale. The SOA controller 30 then develops its throttle signal 28 to the fuel pumping system 35.
An SOA computer, with the necessary added hardware for additional programming, can be programmed by those expert in the art to process the input data of this invention to modify the SOA cruise control signal. Testing for a given engine with an actual truck could be used to establish the best algorithms and constants for the programmed relationships and derived signals. Also, by state-of art programming the controller might be designed to teach itself the best way to control fuel flow for best economy in the combination of speed and fuel mileage. This self teaching could be developed under actual truck travel during which the techniques of override of the cruise control for improved fuel mileage would be carried out by the driver and imposed on the programming of this invention.
Once the computer programming approach is taken to modify the workings of an SOA cruise control by adapting it to incorporate slope change and acceleration, an unlimited number of computer and computer programming means can be developed for this invention by those skilled in the art of computer control. The diagrams presented in the figures are only samples of what might be done. After choosing a computer design and programming it for the functions of this patent, the programmer would take into account the practical needs for changes in fuel flow under actual operating conditions. Examples of these are as follows:
(1 ) As a climbing truck approaches the crest of a hill and the positive slope of the road starts to taper off, good fuel economy requires that the fuel flow be reduced more than a conventional speed control would do. The hill is best finished at the climbing speed achieved before slope reduction. Changing slope combined with changing acceleration allows the computer to anticipate leveling off of the road or change to a negative slope better than would an SOA speed control. By measuring the acceleration of speeding up and at the same time detecting decreasing slope, the control of this invention can effect more efficient climbing as it calls for a lower fuel flow.
(2) When a truck is moving down a steep enough grade that the speed setting is almost reached without the use of fuel, addition of fuel at a low flow rate is an inefficient use of fuel. This would commonly happen with SOA speed controls. For good fuel economy it would be better to use no fuel and proceed down the hill at slightly less than the desired speed. This can be accomplished by the invented system. For example, in FIG. 1, if the computer 1 sees a signal 20 of an appreciable negative slope and a speed 5 no lower than, say, 5% below the set speed 3, the computer 1 shuts off fuel for the sake of better fuel mileage. If the computer sees a signal of a speed 5 of no more than, say, 5% above the set speed 3 and a positive slope 14, for better fuel mileage the computer 1 would set at 18 a fuel rate 2 higher than that set if the slope signal 20 indicated level ground. Such a setting would be especially helpful if slope were to be steadily increasing.
(3) Without having a measurement of the wind, the computer will "see" the wind effect as a changed speed in the absence of a change in fuel flow or slope. An SOA cruise control tends to surge engine power as variable winds cycle the truck speed up and down. This results in reduced fuel mileage compared to steady fuel flow. Under wind surges, changes in fuel rate can be delayed by this invention such that the range of variable fuel rates under surging winds is minimized.
(4) Fuel economy can be helped if the tuck is held to accelerate, even if the truck is lightly loaded, as if the truck were heavily loaded. The computer can be programmed to achieve this by limiting fuel flow to hold acceleration within a given range. With startup on an uphill or downhill path the best acceleration can be programmed via fuel flow rate taking slope into consideration.
(5) It is best to try to maintain momentum going into a hill. If the truck were to receive a gust of tail wind just as a hill climb were started, an SOA cruise control would reduce fuel flow in reaction to the ensuing speed increase, while the present invention would not because it would sense the positive slope as well as the speed increase.
Table I summarizes the control measures of this invention which override the SOA cruise control.
TABLE I______________________________________Road Condition Programmed Action______________________________________Perceived slope increase An increase in fuel flow is imposed on the cruise control in some proportion to the slope increase.Perceived slope decrease Velocity is held constantNegative slope and speed no Fuel cutoffless than a specified fractionof set speedSpeed change with no slope Fuel flow constant for a pre-setchange intervalAcceleration from speed under Fuel flow restrictiona pre-set velocity______________________________________
The relationship between slope and the best fuel flow signal at any one time can be developed with a truck equipped with a recorder of slope, speed, acceleration and fuel flow setting. The truck is then driven in a manner for improved fuel mileage as well as at expeditious speed and with override of the cruise control at the points in travel singled out by this invention for fuel mileage improvement. Once the recording has been made under every possible road slope condition and even with both a light load and with a heavy load, the data are then processed into "look-up" tables for a computer program to be used in computerized cruise control involving slope. The same approach can be used to develop a program in which truck acceleration or deceleration is used as well as slope. As to the programming which provides steady speed for cruise control under conditions of gusting winds, recordings of speed changes under such winds could help establish criteria for appropriate dampening of the fuel flow setting, or a cut-and-try approach could be used by programming logically the dampening and then testing on the road for effectiveness--then making changes for perfection of the approach. The program for fuel shut-off during descent where adequate speed would still be maintained could be, again, programmed using simple calculations and then be adjusted after testing on the road.
The present embodiments are to be considered in all respects as illustrations and not restrictive and all changes coming within the meaning and equivalency range are intended to be embraced herein. The depictions in the figures are not intended to limit the invention to the indicated steps in computer handling of the prescribed input data to manage fuel flow rate in maintaining or approaching a set speed. Any number of computer hardware sets and any number of computer programming methods can be used to implement the concept. The goal of incorporating slope change and acceleration into the control would be to establish the possible fuel mileage gains over operation under SOA cruise control alone. | An automatic control of speed for a vehicle is based on using speed setting, actual speed, acceleration and the change of the slope of the road to set fuel flow for improved fuel mileage. The proposed system of sensors and a programmed computer automatically manages fuel flow to the engine as the truck moves in gusting winds and through transitions from one slope of the road to another. As the conventional cruise control operates to maintain or change speed according to a speed setting Vs the actual speed, the added control of this invention results in a modification of the signal to fuel flow depending upon what road slope change and acceleration is detected. The result is an improvement in fuel mileage. | 1 |
This application claims priority from European Patent Application No.14188458.5 filed Oct. 10, 2014, the entire disclosure of which is hereby incorporated herein by reference.
The invention relates to a race start assistance method for a boat participating in a regatta. It also relates to the device implementing the method.
BACKGROUND OF THE INVENTION
In a regatta race, boats must not cross the start line before the start signal, otherwise they have to turn round and cross the start line again.
The start line may be defined by the position coordinates of two points defining a virtual line.
In these regatta races, the aim is not only to cross the start line first while observing the start signal, but also at a speed closest to the maximum speed of the boat.
In a regatta race, the competitors have a pre-start, which takes place 5 minutes before the start signal, for manoeuvring in order to cross the start line in an optimal manner.
There is a known assist device for crossing the start line including a means for creating a virtual start line, a means for instantaneously knowing the position of the boat with respect to the virtual line, a means for knowing the instantaneous speed of the boat and calculation means for indicating distance with respect to the virtual start line and the time remaining until the start signal.
Using this knowledge of the remaining distance and remaining time, the boat must adjust its speed to cross the line, which leaves the skipper of the boat many choices and therefore uncertainties.
If the skipper has to manoeuvre the boat to adjust to this information, this will affect the start.
SUMMARY OF THE INVENTION
It is an object of the invention to provide a product and its method of operation which offers a simpler and more reliable way of managing the start of a regatta while remaining intuitive.
To this end, the invention relates to a race start assistance method for a boat participating in a regatta including a pre-race with a duration T before the crossing of the start line, the method including a first step intended to permit the creation and storage of the start line in virtual form, and the determination of the instantaneous speed of the boat and its position with respect to the start line, in order to provide at least one indication on how to proceed in the pre-race, the method being characterized in that:
in a second step, prior to the race, at least one race start is simulated by performing a pre-race test, to measure and store, at least once, a parameter that is the maximum speed or test speed of the boat, to deduce therefrom a maximum distance that could be travelled during the pre-race duration if the boat moved at said test speed and thereby to determine the position of a line called the maximum distance line; and in a third step, after positioning the boat between the maximum distance line and the start line, a countdown period is started during which, on the one hand, the distance line moves towards the start line at the test speed while the boat also moves towards the race line at a lower speed than the maximum test speed and during which, on the other hand, the actual motion parameters of the boat are compared to the movement of the distance line to provide indications on the closeness of the distance line to the boat to enable the boat to adjust its speed and/or route so that when the distance line catches up with the boat, said boat is moving at the same speed as said distance line.
In a first advantageous embodiment, during the second step, the maximum speed is stored several times, and the maximum speed of the distance line is the mean of the stored maximum speeds.
In a second advantageous embodiment, the indications as to how to proceed are in digital form or in visual form.
The invention relates to a race start assistance device for a boat competing in a regatta, including a calculator, a satellite positioning means, a storage means, a means for entering information relating to a start line position in the calculator and/or the storage means,
this device being characterized in that it includes means for pre-determining a maximum test speed, means for calculating a separation distance corresponding to the calculated maximum speed multiplied by a time corresponding to the duration of a pre-race, means for simulating the movement of a distance line at the test speed, means for comparing the speed and the position of the boat with respect to the movement of the distance line, means for providing indications as to the difference in speed and/or the distance between the boat and the distance line and display means.
In a first advantageous embodiment, the device includes means for calculating the evolution of the speed of the boat so that its motion coincides with an optimised motion with respect to the start line to be crossed.
In a second advantageous embodiment, the device is integrated in a portable object, such as a mobile telephone or a tablet.
In a third advantageous embodiment, the device is integrated in a watch.
In a fourth advantageous embodiment, the display means are digital or visual.
In another advantageous embodiment, the display means include at least one hand moving with respect to a scale mark.
In another advantageous embodiment, the display means include indicator lights having a first colour, one indicator light having a second colour and indicator lights having a third colour, so that the indicator lights having a first colour are illuminated in the event of a lag position, the indicator lights having a third colour are illuminated in the event of an ahead position and the indicator light having a second colour is illuminated in the event of an optimum position.
In another advantageous embodiment, the watch crystal is touch-sensitive.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be clearly understood with the aid of the following description given by way of non-limiting example with reference to the drawing in which:
FIG. 1 shows a view of a body of water showing the start line and the boat.
FIG. 2 shows a schematic view of an assistance device for regattas.
FIGS. 3A and 3B show views of a body of water showing the distance line at its maximum distance from the start line.
FIG. 4 shows a view of the body of water of FIG. 1 , with the countdown started.
FIG. 5 shows a view of the body of water of FIG. 1 , with the boat moving at the same speed as the distance line.
FIG. 6 shows a view of a watch fitted with the assistance device.
FIG. 7 shows a view of a variant embodiment of a watch fitted with the assistance device.
DETAILED DESCRIPTION
Referring to the various Figures, a body of water for a boat regatta is illustrated.
FIG. 1 shows the start line 2 , which can be determined from two geographical points A, B whose coordinates are, for example, data provided by geostationary satellites. A boat 1 , which has to cross start line 2 , is also illustrated.
The start of a regatta is an important moment. Indeed, the boats must cross the start line after the start signal and at the highest speed, because if the start line is crossed before the start signal, the competitor must turn round and then cross the line again in the right direction.
Further, if, to avoid crossing the line too soon, the competitor very suddenly drops his speed, he will require time to pick up speed again and will make a poor start.
A portable apparatus 100 , using a race start assistance method for a boat participating in a regatta, is therefore used.
Portable apparatus 100 , visible in FIG. 2 , will include a calculator 10 for the overall control of the portable apparatus. Portable apparatus 100 further includes a satellite positioning means 11 , a storage means 12 for data storage and a means 13 for entering information relating to a start line position in the calculator and/or the memory. This means 13 may be one or more buttons or touch-sensitive means.
These means will be supplemented by means 14 or pre-determining a maximum test speed associating, for example, a time base and the positioning device to determine a speed. However, it is also possible for the speed to be obtained from an external apparatus.
Calculator 10 which could be a microprocessor or microcontroller, will include means 10 A for calculating a separation distance corresponding to the calculated maximum speed multiplied by a time T corresponding to the duration of a pre-race, means 15 for simulating the movement of a distance line at the test speed Vm, means 16 for comparing the speed and the position of the boat relative to the movement of distance line L and means 17 for providing indications as to the difference in speed and/or the distance between the boat and the distance line.
It also includes means for calculating the evolution of the speed of the boat so that its motion coincides with an optimised motion relative to the start line to be crossed, and display means 19 .
During a first step visible in FIG. 1 , the geographical points forming the start line are stored in said object. These geographical points can be entered manually or downloaded or stored by positioning oneself on a point on the start line using a GPS device and then pressing a button of the portable object to store the position. The operation is repeated to obtain the second point in order to delineate the start line.
This method then includes a second step or preparatory step having a duration T.
During this second step, which is shown in FIG. 3A , at least one race start is simulated in order to measure and store at least once a parameter which is the maximum speed Vm or “test speed” of the boat via speed determining means 14 . This simulation takes the form of a pre-race test in real conditions. This speed information is used by means 10 A to calculate a maximum separation distance D which could be travelled during pre-race duration T if the boat moved at said test speed, and thereby determine the position of a maximum distance line L. This distance D is stored by calculator 10 via storage means 12 . The latter may be a flash memory.
In a third step or race start step, boat 1 is positioned between maximum distance line L and start line 2 . A countdown with a duration T is then started.
During this countdown, the calculator moves distance line L towards the start line at test speed Vm as seen in FIGS. 4 and 5 .
Using the calculator, the position and/or actual motion parameters of boat 1 are then compared to the movement of distance line L. In fact, the boat may be stationary or moving slightly.
This calculator 10 thus provides indications on the closeness of distance line L to boat 1 to enable boat 1 to adjust its speed V and/or its route. This makes it possible, when the distance line catches up with boat 1 , for said boat 1 to move at the same speed as that of said distance line.
Consequently, gradually over time, boat 1 will accelerate and distance line L will move closer to the boat. The difference in speeds will be limited, as will the distance between the distance line and boat 1 . Parameters can therefore be calculated to allow the speed and/or the route of boat 1 to evolve so that its motion coincides with the movement of distance line L, obviously before crossing the start line 2 .
It will be understood that the various measurements, such as that of the distance between boat 1 and start line 2 , take into account the relative position of the boat. Indeed, depending on the wind direction, boat 1 may not always sail in a straight line.
This fact implies the existence of an actual distance and a relative distance. The actual distance d 1 is the shortest distance between boat 1 and start line 2 , whereas the relative distance d 2 is the distance between boat 1 and start line 2 taking into account the direction of the boat. Actual distance d 1 passes through a line perpendicular to start line 2 . Relative distance d 2 is calculated by determining the angle α between the line perpendicular to start line 2 which is actual distance d 1 and the straight line formed by the direction of the boat as seen in FIG. 3B , d 2 =d 1 /cos α.
Consequently, calculator 10 is capable, depending on the position and direction of boat 1 , of determining actual distance dl and relative distance d 2 . It will be understood that, for the start of a regatta, actual distance dl is the important distance, because boat 1 is capable of tacking, so the relative distance is unstable since it varies with angle α whereas the actual distance remains stable. The object is for the speed and the position of boat 1 to be such that the end of its travel during the pre-race coincides, as regards both the distance from start line 2 and speed, with the movement of distance line L which represents the optimised crossing of start line 2 .
To achieve this, the device provides boat 1 with information, for example, the difference in speeds, the distance between distance line L and the position of boat 1 and predicted speed change instructions.
This information is provided by information means 20 and display means 19 . Information means 20 may either take a digital form, i.e. numbers, or the form of visual indications, such as indicator lights 21 or hands 22 moving with respect to a scale mark.
Preferably, the information is presented in the form of visual indications. Indeed, these visual indications are easier to understand given that the boat driver has other tasks to attend to. For example, indicator lights may gradually be illuminated or colours may be used.
Where colours are used, one example may include a plurality of indicator lights in the form of segments. These indicator lights may be of different colours, the colours being associated with a particular piece of information.
In an example of the invention shown in FIG. 6 , the portable object is provided with 11 indicator lights. In detail, there will be 5 indicator lights having a first colour 21 a , one indicator light having a second colour 21 b and 5 indicator lights having a third colour 21 c.
When the countdown is started, the 5 indicator lights having a first colour 21 a are illuminated. The first colour may be red. When distance line L moves closer, some indicator lights will go out, so that the closer distance line L becomes, the lower will be the number of illuminated indicator lights 21 a . At that moment, boat 1 accelerates.
When distance line L is level with boat 1 and the speed of distance line L is close to the speed of boat 1 , the indicator light having a second colour 21 will light up. The second colour may be green. This means that boat 1 is in an optimum phase, i.e. it is at the right distance and right speed to cross start line 2 in an optimal manner.
If the indicator lights having a third colour 21 c start to light up, this means that the boat is ahead of distance line L and that it must slow down. The third colour may be orange.
Thus, by means of a left-right apportionment it is possible to indicate whether boat 1 is ahead, in line with or behind its motion curve according to the illuminated colour. The skipper is capable of knowing whether he is ahead of (orange), behind (red) or within the required timing (green).
This also makes it possible to indicate whether the boat is significantly ahead or behind by means of the number of illuminated indicator lights 21 .
Of course, it is possible to envisage the indicator lights taking the form of three bars each of a different colour. The bars indicating whether the boat is ahead or behind are then formed by a plurality of areas so that the further ahead or behind the boat is, the greater will be the number of illuminated areas.
These means are contained in a cover of a portable object, such as a telephone, a tablet or a watch case.
The speed of motion of boat 1 can be obtained by GPS type satellite positioning. Pressing on a watch button or on the telephone keyboard also makes it possible to store the maximum speed. It is also possible to obtain this speed using an external sensor.
The device may therefore, as shown in FIG. 7 , include a dial comprising a hand 22 A which, in the 12 o′clock position indicates that the difference between the instantaneous speed and the distance line speed is equal to zero. If the hand moves towards the right on a scale 22 B, this could mean that the instantaneous speed is greater than the distance line speed and therefore it is necessary to slow down, and if the hand moves towards the left that the instantaneous speed is insufficient. The amplitude of angular motion gives an idea of the significance of the difference, it is also possible to place the hand facing an explicit pictogram representing, for example, a − sign or a + sign.
A second hand 22 C may, like the preceding hand, indicate the distance that separates the distance line from the boat on a scale 22 D.
Instead of hands, there may be pie-shaped segments.
Given that the simulation occurs before the race, weather conditions can be taken into account by calculating the mean of various tests. This mean could be affected by a corrective measure depending on the wind speed measured at the time of the race. The maximum speed of the distance line may be the mean of several simulations.
It will be clear that various alterations and/or improvements and/or combinations evident to those skilled in the art may be made to the various embodiments of the invention set out above without departing from the scope of the invention defined by the annexed claims.
Storage means 12 could be a rewritable semiconductor mass memory utilising NOR or NAND technology.
Further, the present invention should not be limited to a portable product such as a telephone, a tablet or a watch case, but could also be a bracelet or a laptop computer. | A race start assistance method for a boat participating in a regatta including a pre-race having a duration before the crossing of the start line, the method including a first step intended to permit the creation and storage of the start line in virtual form, and the determination of the instantaneous speed of the boat and its position with respect to the start line, in order to provide at least one indication on how to proceed in the pre-race. | 1 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This patent application is the U.S. national phase, under 35 USC 371, of PCT/DE03/01330, filed Apr. 24, 2003; published as WO 03/097359 A1 on Nov. 27, 2003 and claiming priority to DE 102 22 294, filed May 18, 2002, the disclosures of which are expressly incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention is directed to dampening systems with devices for the inflow and for the return flow of a dampening agent. The dampening system includes at least one dampening ductor, a dampening agent tank, an inflow device and a return flow device.
BACKGROUND OF THE INVENTION
[0003] Dampening systems are used in offset printing presses and in other printing systems. A dampening system consists of, for example, a dampening ductor, which may also be called a water tank roller, a dampening agent tank, and devices for supplying and returning dampening agent to and from the dampening agent tank. The dampening ductor or roller is typically partially immersed in the dampening agent contained in the dampening agent tank, picks up the dampening agent by a rotating movement, and transfers the dampening agent to further rollers of the printing group. To prevent interferences with the printing operation, it is important that the dampening agent taken up by the dampening ductor or roller has identical physical and chemical properties over the entire length of the roller.
[0004] A dampening system in an offset printing press is described in DE 198 53 362 C1. A supply system for dampening agent, which has a plurality of spray nozzles over the roller length, is assigned to the dampening ductor in the axial direction of the ductor.
[0005] A dampening system is known from DE 196 16 198 A1, which system has at least one dampening agent pickup roller. A dampening agent supply line is arranged above the dampening agent pickup roller, parallel with this roller, and extends over the roller's full length. On its underside, the supply line is provided with outlet openings, by the use of which a water curtain is formed when the supply line is charged with dampening agent.
[0006] For use in removing deposits, such as ink particles, for example, from a dampening ductor or roller, DD 247 414 A1 proposes to press a stripping element against the surface of the roller with a pressure which is equal over the entire length of the roller.
[0007] A dampening agent recirculating system for offset printing presses is described in EP 0 638 417 A1. In this case, a dampening agent supply line, with hole-shaped cutouts, and a dampening agent catch rod, which is situated at a defined small distance from the dampening ductor, are positioned parallel to the dampening ductor or roller.
[0008] DE 94 20 343 U1 shows a dampening system, whose dampening agent tank has an inflow line with several openings. A return conduit, having a weir, extends over the entire length of the dampening agent tank.
[0009] DE 199 09 262 A1 describes a dampening agent tank with a dam for limiting the return flow of the dampening agent. A filter has been installed between this dam and a return flow line.
[0010] DE 38 31 741 A1 discloses a dampening agent tank with several inflow lines and with several return flow lines.
[0011] DE 17 61 908 A discloses an adjustable dampening supply device.
SUMMARY OF THE INVENTION
[0012] The object of the present invention is directed to providing dampening systems with dampening agent inflow and return flow devices.
[0013] In accordance with the present invention, the object is attained by the provision of a dampening system having at least one dampening fluid ductor or roller, a dampening agent tank, an inflow device and a return flow device. The inflow device has several distributing tubes, each typically with several openings, that are assigned to the ductor. At least one inflow line of the distributing tube is arranged between last openings of first and second ends of the distributing tube. The return flow device has a collecting tank that is connected with the dampening agent tank, which collecting tank extends in the longitudinal direction of the ductor and is double walled.
[0014] The advantages to be gained by the present invention consist, in particular, in that the dampening ductor or roller is arranged in the dampening agent tank between the inflow device and the return flow device for the dampening agent. The inflow device and the return flow device are configured in such a way that the inflow and the return flow of the dampening agent in the area of the dampening ductor are both distributed to several locations. In the course of conducting new or fresh dampening agent from a dampening agent reservoir to the dampening agent tank, uneven intermixing of newly supplied dampening agent with dampening agent already present in the dampening agent tank can occur at some locations in the dampening agent tank. Areas of the dampening agent tank, in which little intermixing takes place, can heat up and can have a temperature which is higher, by up to 10° C., in comparison with areas of the dampening agent tank in which a constant exchange between newly supplied dampening agent with the dampening agent already present in the dampening agent tank takes place. Since the viscosity of the dampening agent depends greatly on the temperature of the dampening agent, and since the print quality, in turn, depends greatly on the viscosity of the dampening agent, the dampening agent taken up from the tank by the dampening ductor must be substantially at the same temperature level over the entire length of the dampening ductor.
[0015] The present invention is directed to the provision of a dampening system wherein a uniform exchange of dampening agent takes place substantially over the entire length of the area of the dampening ductor.
[0016] This objective is achieved in accordance with the present invention because several locations for the inflow of dampening agent, called dampening agent inflow locations, are assigned to the front of the dampening ductor, and several locations for the return of dampening agent, called dampening agent return flow locations, are assigned to the rear of the dampening ductor. Thus, the dampening ductor is located in the area of a flow of dampening agent which is formed by both the inflow and the return flow of the dampening agent into or out of the dampening agent tank. The locations for the inflow and for the return flow are matched to each other in such a way that a uniform intermixing of newly supplied dampening agent with that already present in the dampening agent tank takes place in the area of the dampening ductor and over its entire roller length. In this way, it is possible, for example, to match the spatial arrangement of the inflow and return flow locations among or between each other.
[0017] A further possibility resides in the configuration of the inflow and of the return flow locations themselves, such as, for example, their geometry, shape and/or diameter. It would also be possible to cause uniform intermixing by a suitable distribution of the charging pressure at the dampening agent inflow locations. In actual use, a combination of these various possibilities will result, wherein the actual configuration will have to be determined by empirical tests. In connection with the principle of uniform intermixing of dampening agent, such as water, in the area of the dampening doctor blade over its entire length, it is important that, on the one hand, that dampening agent is supplied at several locations in the area of the dampening ductor and, on the other hand, dampening agent is returned at several locations in the area of the dampening doctor blade in order to assure a continuous exchange of dampening agent in the area of the dampening ductor.
[0018] In accordance with a preferred embodiment of the present invention, the dampening agent inflow device is arranged at the dampening agent tank as a separate component. This is of particular advantage if the inflow device must periodically be disassembled, for example because it has become damaged or dirty. In the present case, it is then possible to remove the inflow device, embodied as a separate component, in a simple and cost-effective manner from the dampening agent tank. Thus, a more cost-intensive disassembly of the entire dampening agent tank is not necessary.
[0019] The dampening agent inflow line is attached substantially at the center of the inflow device. This has the advantage that, following the charging of the inflow line with dampening agent, an almost identical dampening agent pressure prevails at all of the dampening agent inflow locations of the inflow device. In this way, a pressure drop, as is the case when the inflow line is located on one side of the inflow device, is clearly reduced.
[0020] To minimize interference effects of the dampening agent flow in the dampening agent tank, it would be sensible to arrange the tubes of the dampening agent inflow line at the side of the dampening agent tank. At the same time, it is conceivable to use the inflow line as a support for the inflow device. This allows a simple and a cost-effective configuration of the inflow line and the inflow device.
[0021] It is of no importance, for the principle of the invention, in which way the inflow device is configured. It is thus possible, for example, to configure the inflow device as a hollow conductor, such as a round tube, for example.
[0022] To provide dampening agent to the dampening agent tank, uniformly distributed over the entire length of the dampening ductor, it is practical for the dampening agent inflow locations, which are embodied as either circular or rectangular cutouts, to be arranged over the entire length of the hollow conductor and to be evenly spaced apart from each other. A further possibility lies in providing a rectangular cutout for the passage of the dampening agent in the hollow conductor, which rectangular cutout extends substantially over the entire length of the hollow conductor.
[0023] In connection with dampening ductors of great length it is not as possible to provide a uniform pressure at all of the dampening agent inflow locations available, even with a central inflow of the dampening agent into the inflow device, which is embodied as a hollow conductor. In this case, it would be sensible for the inflow device to consist of at least two hollow conductors, which are arranged one behind the other in the longitudinal direction. Each one of these hollow conductors may be separately provided with dampening agent by the use of an inflow line and wherein the two hollow conductors are functionally separated from each other.
[0024] In accordance with a further preferred embodiment, the return flow device consists of at least two cutouts which are arranged in the bottom of the dampening agent tank, and through which the dampening agent can be returned from the dampening agent tank to the dampening agent reservoir. To achieve a uniform removal of the dampening agent from the dampening agent tank it would furthermore be appropriate to arrange the cutouts so that they are parallel with respect to the longitudinal axis of the dampening ductor. A return flow device configured in this way can be accomplished in a particularly simple and cost-effective manner.
[0025] It is particularly advantageous, in accordance with the present invention, if the return flow device has a comb-shaped component which is arranged upstream of the cutouts in the bottom of the dampening agent tank. The comb shape of the component is constituted by alternating areas of tooth-shaped elevations and indentations, wherein a cutout in the bottom of the dampening agent tank is assigned to each indentation area. The comb-shaped component is arranged parallel with respect to the longitudinal axis of the dampening ductor. The comb-shaped component extends over the entire length of the dampening doctor blade, and the tooth-shaped elevations point vertically upward. A type of increase of the cross section of this area is accomplished by the provision of the indentations, because of which increase the dampening agent can preferably flow into the cutouts arranged downstream of the indentations and is removed in this way, from the dampening doctor blade over the entire length of the latter.
[0026] Due to the large temperature difference between the dampening agent and the ambient air it would be prudent to configure the lines for the inflow and for the return flow of the dampening agent into or out of the dampening agent reservoir to be double-walled to achieve some sort of thermal disconnection between the lines conducting dampening agent and the ambient air. Without a thermal disconnection, any moisture contained in the air can condense on the lines charged with dampening agent. Drops of condensate are formed, which drops can settle, for example, in the area of the printing group and/or onto the web of material to be imprinted, which drops can also lead to interference with the printing operation.
[0027] The hollow space of the double-walled inflow and return flow lines is filled with an insulative foam.
[0028] To match the temperature of the new dampening agent supplied from the dampening agent reservoir, in particular in such a way that the dampening agent received on the dampening doctor blade over its entire length has substantially the same temperature, it would be beneficial for a temperature measuring device to be provided in the area of the dampening agent doctor blade in at least two locations. The temperature measuring device can be coupled with a control and/or with a regulating device, by the use of which, the temperature of the supplied dampening agent is regulated.
BRIEF DESCRIPTION OF THE DRAWINGS
[0029] Preferred embodiments of the present invention are represented in the drawings and will be described in what follows.
[0030] Shown are in:
[0031] FIG. 1 , a side elevation view, partly in cross-section, of a preferred embodiment of a dampening system with a dampening agent tank, a dampening ductor and devices for the inflow and return flow of dampening agent in accordance with the present invention, in
[0032] FIG. 2 , a front view, partly in cross-section, of a dampening system in accordance with FIG. 1 and taken in the sectional direction A shown in FIG. 1 , and without the comb-shaped component, and in
[0033] FIG. 3 , a front view, partly in cross-section of a dampening system in accordance with FIG. 1 in the sectional direction B shown in FIG. 1 and without the dampening ductor.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0034] A dampening system in accordance with the present invention, with devices for accomplishing the inflow and the return flow of a dampening agent 01 into or out of a dampening agent tank 02 , is represented in FIG. 1 . A dampening ductor or roller 03 is attached between an inflow device 04 , as seen in FIG. 2 , and a return flow device 06 . The inflow device 04 is arranged opposite the front side of the dampening ductor 03 .
[0035] For improved understanding it should be pointed out at this juncture that the inflow device 04 consists of at least one distributing tube 18 with several openings 07 . This is shown most clearly in FIG. 2 .
[0036] In the present preferred embodiment, the distributing tube 18 is provided as a separate component in the dampening agent tank 02 , as represented in FIG. 2 , and is preferably substantially located completely below the liquid level of the dampening agent 01 . Moreover, the distributing tube 18 is embodied as a hollow conductor 18 in the form of a round tube 18 and has an interior tube diameter of approximately 10 mm to 20 mm, and in particular has a diameter of 12 mm. A longitudinal axis of the distributing tube 18 extends parallel with a longitudinal axis of the dampening ductor 03 . The length of the distributing tube 18 extends substantially over the length of the dampening ductor 03 .
[0037] As can also be seen by referring to FIG. 2 , the dampening agent inflow locations 07 , which are embodied as circular cutouts 07 , are arranged over the entire length of the distributing tube 18 . These circular cutouts 07 point or face in a direction toward the dampening ductor 03 . By charging the distributing tube 18 with dampening agent 01 , this dampening agent 01 can then exit through the dampening agent inflow locations 07 , so that dampening agent 01 is supplied to the dampening agent tank 02 substantially over the entire length of the dampening ductor 03 . The distal ends of the distributing tube 18 are each closed, so that no dampening agent 01 can flow out of them. In the present preferred embodiment, the circular cutouts 07 are spaced at equal distances from each other and all have the same diameter. The diameter of each of the circular cutouts 07 lies, for example, within a range of from 1 mm to 5 mm, and is, in particular, 3 mm.
[0038] The cross section or area of each of the circular cutouts 07 corresponds to approximately 25% of the diameter of the round tube 18 .
[0039] The flow path of the dampening agent 01 between the distributing tube 18 and the dampening ductor 03 is identical over the entire length of the dampening ductor 03 because of the parallel orientation of the dampening ductor 03 and the distributing tube 18 . Because the plurality of dampening agent inflow locations 07 are arranged opposite the dampening ductor 03 over substantially its total length, it is possible to supply the dampening agent tank 02 uniformly with dampening agent 01 over substantially the entire length of the dampening ductor 03 .
[0040] The distributing tube 18 is provided with dampening agent 01 from a dampening agent reservoir, which is not specifically represented, through an inflow line 08 . To achieve a substantially uniform pressure of the newly supplied dampening agent 01 arriving at all of the dampening agent inflow locations 07 of the distributing tube 18 , embodied as a round tube 18 , and flowing into the dampening agent tank 02 to mix with the dampening agent 01 already in tank 02 the inflow line 08 is arranged centered along the length of the distributing tube 18 . In contrast to a one-sided inflow of the dampening agent 01 into the distributing tube 18 , with the length of the distributing tube 18 being the same, the dampening agent 01 travels over a substantially shorter flow path before exiting through the dampening agent inflow locations 07 . Moreover, with the inflow line 08 arranged in the center of the distributing tube 18 , and with an identical number of dampening agent inflow locations 07 , only approximately half as many of the dampening agent inflow locations 07 are arranged in series one behind the other in comparison to the orientation that would exist in a one-sided inflow. Because of this configuration, a considerably reduced pressure difference between dampening agent inflow locations 07 spaced far apart from each other, and thereby a substantially identical pressure of the outflowing dampening agent, can be achieved at all dampening agent inflow locations 07 .
[0041] In the present preferred embodiment, the dampening agent inflow line 08 is embodied in the form of a bent round tube 08 , which is either of one piece construction, or which can consist of several components, which are, for example screwed together, welded together or hard-soldered. The connection between the distributing tube 18 and the inflow line 08 can also be provided by a screw connection, a welded connection or a hard-soldered connection. The inflow line 08 at the same time takes on the function of a support for the distributing tube 18 , so that a separate frame for holding the distributing tube 18 in the dampening agent tank 02 can be omitted. In order not to negatively affect the essential function of the dampening system, which could be the case if, for example, the flow of the dampening agent 01 through the tubes of the inflow line 08 were interfered with, the inflow line 08 runs on the side of the dampening agent tank 02 adjacent the bottom of the dampening agent tank 02 .
[0042] In a further preferred embodiment, which is not specifically represented, several distributing tubes 18 can be assigned to the dampening ductor 03 . Each one of these several distributing tubes 18 has its own inflow line 08 .
[0043] At least one inflow line 08 of the distributing tube 18 is arranged between a last opening 07 of a first distal end and a last opening 07 of a second distal end of the distributing tube 18 . The inflow line 08 is, in particular centered along the length of the distributing tube 18 . In the case of several inflow lines 08 for a single distributing tube 18 , these several inflow lines 18 are arranged approximately uniformly distributed in relation to the longitudinal direction of the distributing tube 18 .
[0044] The two last openings 07 of the distal ends of the distributing tube 18 are spaced at a distance IO 1 from each other, as seen in FIG. 2 . A further distance 102 is defined between the last opening 07 and the inflow line 08 .
[0045] The following relationship applies: IO2= IO1 / N+1′ wherein N is the number of inflow lines 08 , and IO 1 is the spacing between the two last openings of the distributing tube 18 .
[0046] For a distance IO 3 between two inflow lines 08 the following applies: IO3≠ IO1 / N+1′ wherein N is the number of inflow lines 08 , and 101 is the spacing between the two last openings of the distributing tube 18 .
[0047] The openings 07 of the distributing tube 18 are arranged below the surface level of the dampening agent 01 in the dampening agent tank 01 , i.e. within the body of the dampening agent 01 . The inflow lines 08 are also arranged, from the side of the dampening agent tank 02 to the center of the distributing tube 18 , within the dampening agent 01 .
[0048] The inflow line 08 of the distributing tube 18 is arranged, at least in part, in the longitudinal direction of the dampening ductor 03 within the dampening agent. This may be seen most clearly in FIG. 2 .
[0049] The return flow device 06 has a double-walled collecting tank 16 . Collecting tank 16 is connected with the dampening agent tank 02 and extends in the longitudinal direction of the dampening ductor or roller 03 , as is seen in FIG. 1 . This longitudinal extension of the collecting tank 16 can also be seen in FIG. 3 .
[0050] The return flow device 06 is arranged in the dampening agent tank 02 opposite to the rear of the dampening ductor 03 . In the depicted embodiment, the return flow device 06 consists of two components, namely cutouts 09 which are located in the bottom of the dampening agent tank 02 for the return flow of the dampening agent 01 which was carried out of the area of the dampening ductor 03 , and a comb-shaped component 12 , which has been placed upstream of the cutouts 09 . The cutouts 09 , which may be formed as circles, have a diameter of from 10 mm to 30 mm, and in particular of 23 mm. The comb-shaped component 12 is oriented parallel with the longitudinal axis of the dampening ductor 03 and extends over the entire width of the dampening agent tank 02 . In the same way, the downstream located cutouts 09 , formed on the bottom of the dampening agent tank 02 , are also arranged parallel with the longitudinal axis of the dampening ductor 03 and extend substantially over the entire length of the dampening ductor 03 .
[0051] The dampening system, in the area of the return flow device 06 , is represented in FIG. 3 , in the cross-sectional direction B and without the dampening ductor 03 . The comb-shaped component 12 and the cutouts 09 arranged in the bottom of the dampening agent tank 02 can be seen in this cross-sectional front elevation view. The comb-shaped component 12 is mounted on the bottom of the dampening agent tank 02 and is oriented perpendicularly with respect to it. In the present preferred embodiment, the comb-shaped component 12 is embodied in the form of a comb plate 12 with tooth-shaped elevations 13 . The tooth-shaped elevations 13 each have a linear extension of from 100 mm to 300 mm, in particular of 200 mm. The elevations 13 , in the form of teeth, are formed so that dampening agent return flow locations 14 , which are substantially embodied by incisions 14 , formed in the top of the comb-shaped plate 12 , are open at the top of plate 12 and are extending parallel to each other, and with rectangular and/or triangular and/or curved bottom transitions. The incisions 14 , as well as the alternating tooth-shaped elevations 13 , are located below the liquid level of the dampening agent 01 in the dampening agent tank 02 . The dampening agent 01 coming from the dampening ductor 03 can flow out of the tank 02 over the entire length of the comb-shaped component 12 . However, a sort of a cross-sectional flow volume increase takes place in the area of each incision 14 , because of which flow volume increase, flowing off dampening agent 01 is conducted out of the area of the dampening ductor 03 preferably in the respective areas of the incisions 14 . A separate cut-out 09 in the bottom of the dampening agent tank 02 is assigned downstream of each incision 14 in the comb plate 12 , and through which cut-out 09 the dampening agent 01 is conducted out of the dampening agent tank 02 into a collecting tank 16 . It is assured by this that, in the area of each incision 14 , the dampening agent 01 can flow off unhindered. The dampening agent 01 that flows out of the dampening agent tank 02 , is returned from the collecting tank 16 to the dampening agent reservoir through a return line 11 . The collecting tank 16 extends in the longitudinal direction of the dampening ductor 03 , as seen in FIG. 3 , and extends, in the transverse direction of the tank 02 and the ductor 03 , at a fraction of the width of the dampening agent tank 02 . The collecting tank 16 has double walls defining a space which is filled with an insulative foam. The incisions 14 in the comb plate 12 , as well as the cutouts 09 in the bottom of the dampening agent tank 02 , are spaced apart from each other at equal distances and extend over the entire length of the dampening ductor 03 . The distance between the tooth-shaped elevations 13 is from 1 mm to 20 mm, and in particular is 5 mm. By the arrangement of the incisions 14 in the comb plate 12 and by the respectively arranged downstream cutouts 09 in the bottom of the dampening agent tank 02 , it is possible to remove dampening agent 01 from the area of the dampening ductor 03 substantially over the entire length of the dampening ductor 03 .
[0052] Analogous to the geometric conditions in the area of the inflow device 04 , the return flow path of the dampening agent 01 between the dampening ductor 03 and the return flow device 06 is also uniform over the entire length of the dampening ductor 03 . This is because of the parallel arrangement of the dampening ductor 03 and the return flow device 06 . Because the dampening agent return flow locations 09 , 14 are arranged opposite each other, over substantially the entire length of the dampening ductor 03 , dampening agent 01 , coming from the direction of the dampening ductor 03 , can be removed from the area of the dampening ductor 03 uniformly over the entire length of the dampening ductor 03 .
[0053] Since the longitudinal axes of the inflow device 04 and of the return flow device 06 extend substantially parallel with respect to the longitudinal axis of the dampening ductor 03 , and to each other, and because the dampening agent inflow locations 07 are arranged on the front and dampening agent return flow locations 09 , 14 are arranged on the back of, and substantially opposite the dampening ductor 03 , and extending over the entire length of the dampening ductor 03 , and further because of the substantially uniform charging with pressure of all of dampening agent inflow locations 07 , it is possible, in a simple way, in accordance with the present invention, to supply dampening agent 01 to the dampening ductor 03 over its entire length and to uniformly remove dampening agent 01 . This means that identical flow conditions prevail for both inflowing and oufflowing dampening agent 01 over the entire roller length, so that a uniform intermixing of freshly supplied, inflowing dampening agent 01 , with dampening agent 01 already present in the dampening agent tank 02 can take place over the entire roller length. A uniform exchange of dampening agent 01 is thus assured over the entire roller length. The uniform, equal exchange of dampening agent 01 is additionally aided by setting the direction of rotation 17 of the dampening ductor 03 to be the same as the flow direction of the dampening agent 01 , as seen in FIG. 1 . Because of the even intermixing of new, inflowing dampening agent with dampening agent 01 already present in the dampening agent tank 02 , the dampening agent 01 picked up by the dampening ductor 03 has identical physical and chemical properties over the entire length of the dampening ductor 03 .
[0054] In place of the cutouts 09 in the bottom of the dampening agent tank 02 , it is also possible to, for example, arrange an additional separating wall, with cutouts 09 , between the dampening agent tank 02 and the collecting tank 16 .
[0055] The size of the inflow and of the return flow at the respective dampening agent inflow locations 07 and at the dampening agent return flow locations 09 , 14 can be adjusted.
[0056] While preferred embodiments of dampening systems having a dampening agent feeding and return device, in accordance with the present invention, are set forth fully and completely hereinabove, it will be apparent to one of skill in the art that various changes in, for example, a drive source for the ductor, the specific constituency of the dampening fluid, and the like could be made without departing from the true spirit and scope of the present invention which is accordingly to be limited only by the following claims. | A dampening system has at least one dampening ductor or roller; a dampening agent bin or trough, which holds a dampening agent, a feeding device, and a return device. The feeding device includes at least one dampening agent distributing pipe that has a number of spaced openings. A number of these dampening agent distributing pipes are assigned to the dampening ductor or roller. | 1 |
FIELD OF THE INVENTION
[0001] The invention pertains to a towed implement with an undercarriage, at least one wheel suspension, a spring member and an adjusting device.
BACKGROUND OF THE INVENTION
[0002] DE-A-31 39 936 discloses a towed agricultural implement with an undercarriage, on the two lateral end regions of which one respective wheel suspension is arranged. Both wheel suspensions include a shaft in the region of their pivoting axis, and these shafts are connected such that they can be moved relative to one another by means of a spring-loaded, transverse swinging arm, namely on the ends that face one another. An adjusting device can be engaged with limit stops on the wheel suspensions in one direction in order to adjust the wheel suspensions in one direction.
[0003] EP-A1-0 149 870 discloses a towed mower in which an adjusting device and a spring member are connected in series. In one of the embodiments described in this publication, an adjusting cylinder acts upon a pivoted shaft that vertically pivots the wheel cranks on the respective end regions by means of braces in the form of gas springs formed by hydraulic cylinders coupled with gas accumulators.
[0004] The known suspension arrangements exhibit a problem which occurs when the mower encounters an obstacle, namely that the spring members need to absorb much energy and, after overcoming the obstacle, abruptly release the stored energy in case of low counter forces, for example when the wheel raises off the ground. This can lead to damage to the adjusting device, wherein the piston may, in particular, impact on the end of the cylinder housing or an inside shoulder and/or undergo damage to the sliding surface or the seals.
SUMMARY OF THE INVENTION
[0005] According to the present invention there is provided an improved suspension arrangement for a towed implement.
[0006] An object of the invention is to provide a suspension arrangement for a towed implement wherein provision is made for damping the rebound of the stored energy so as to prevent damage to the hydraulic or pneumatic actuators.
[0007] A more specific object of the invention is to provide a suspension for a towed implement including damping arrangements using coil or disc springs, gas pressure reservoirs or rubber-like elements.
[0008] Yet a more specific object is to provide a suspension, as set forth in the foregoing objects, wherein the damping arrangements may include devices that are relatively inexpensive and readily available on the market such as a coil spring or disk spring that is arranged around a piston rod in a cylinder housing, or a caoutachouc mass in the form of a ring or the like could be inserted between the end of the cylinder housing and the piston; and/or a gas pressure reservoir could be connected to a second piston chamber.
[0009] Yet another object of the invention is to provide a second embodiment wherein the wheel suspension includes a reversing link which operates when pivoted in a first direction to direct forces such that a gas spring accumulator that is coupled to a hydraulic cylinder connected to the reversing link acts so as to cushion loads caused when the wheel passes over an obstacle and, when pivoted in a second direction by the force of a suspended wheel returning to its operating position, also acts to cushion this movement of the wheel.
[0010] These and other objects will become apparent from a reading of the ensuing description together with the appended drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] [0011]FIG. 1 is a schematic left side elevational view of a towed implement equipped with a suspension constructed in accordance with a first embodiment of the present invention.
[0012] [0012]FIG. 2 is a schematic representation of an adjusting device with a spring member and a damping device constructed in accordance with the first embodiment of the invention.
[0013] [0013]FIGS. 3 through 6 are views of the adjusting device of FIG. 2 shown in respective first, second, third and fourth operating states.
[0014] [0014]FIG. 7 is a schematic representation of a second embodiment of the adjusting device incorporating a reversing link together with a spring member and a damping device.
DESCRIPTION OF THE PREFERRED EMBODIMENT
[0015] The towed implement 10 , shown in FIG. 1, includes an undercarriage 12 , wheels 14 , wheel suspensions 16 , a spring arrangement 18 , adjusting devices 20 and a working unit 24 .
[0016] The implement 10 is constructed in the form of a mower-conditioner that serves for cutting, processing and depositing stalk crops on the ground. While in operation, the implement 10 is towed over uneven terrain with a relatively high speed and constantly subjected to shocks that, in addition to the flexibility of the wheels 14 , need to be absorbed by the spring arrangement 18 . However, the invention is by no means limited to an implement of this type, but can also be used in other towed implements, e.g., balers, soil conditioning tools, saws, sprayers and the like.
[0017] The undercarriage 12 is essentially constructed in the form of a frame that has the shape of an upside-down “U” with vertical limbs 26 and a horizontal crossbeam 28 , in the intermediate space of which the working unit 24 is at least partially accommodated. The undercarriage 12 carries the working unit 24 in a fashion described in greater detail below, and together with the working unit can be adjusted to different elevations in reference to the ground.
[0018] A wheel 14 , that is conventionally provided with a pneumatic tire, is connected in the lower region of each limb 26 , such that it can be vertically pivoted, namely by means of the wheel suspension 16 , which includes a trailing link having its forward end pivotally coupled to the limb 26 and carrying at its rear end a spindle on which the wheel 14 is rotatably mounted. Thus, the undercarriage 12 is supported on the ground by the wheels 14 .
[0019] A holder or bracket 32 is situated in the upper region of each limb 26 . In addition, a bearing 36 located in a rear region of an upper longitudinally extending arm 38 forms part of a pivotal coupling of the arm 38 to the crossbeam 28 . Further, a bearing 40 forms part of a vertical pivotal axis about which a forward section of the tongue 22 is connected for pivoting horizontal relative to a rear section that is fixed to the cross beam 28 . Receivers 42 for springs 44 are also provided on each side of the crossbeam 28 .
[0020] Each wheel suspension 16 further includes a connection or bracket 46 located at the upper rear portion of the trailing link, and extending between the brackets 32 and 46 is an extensible and retractable motor 60 of the adjusting device 20 . The motor 60 , which is constructed in the form of a single-action hydraulic motor that is pressurized to effect its extension, can also be considered to form part of the wheel suspension 16 . A lower suspension link 52 cooperates with the upper link 38 to form a four-bar linkage and has its rear end coupled to the trailing link by a pivot pin 50 , and has its forward end coupled to a lower rear region of the working unit 24 .
[0021] The spring member arrangement 18 includes a gas pressure reservoir 56 that acts as a spring element. Although the gas pressure reservoir 56 is common to both motor operators 60 forming part of the adjusting device 20 in FIG. 2, it would also be conceivable to provide a gas pressure reservoir 56 for each of the motor operators 60 . The gas pressure reservoir 56 is connected to a shared supply line 30 for both motor operators 60 which ends in a generally known three position, three way hydraulic valve 34 and makes it possible to receive the pressure medium from a pump 62 or to release a pressure medium into a reservoir 64 by means of this hydraulic valve 34 . The hydraulic valve 34 , the pump 62 and the reservoir 64 are schematically shown in FIG. 2, for simplicity, with it to be understood that they replace a generally known hydraulic system that, however, is significantly more complicated to realize. The control of the motor operators 60 is accomplished remotely from the towing vehicle (not shown). The gas pressure reservoir 56 has such dimensions that its gas cushion is not compressed when the motor operator 60 is extended, and is subjected to the system pressure. The gas cushion is only compressed when the implement 10 more or less abruptly encounters an obstacle and the motor operators 60 are subjected to shocks.
[0022] Referring now also to FIGS. 3 - 6 , it can be seen that a damping device 48 is incorporated in each of the operators 60 . Specifically, each operator 60 includes a cylinder housing 66 and a piston 68 with a piston rod 70 which is able to slide in the cylinder housing 66 . One end of the cylinder housing 66 is closed and connected to a supply line 30 , wherein the other end of the cylinder housing is closed by a plate 72 , through which the piston rod 70 extends. The cylinder housing 66 is connected to the undercarriage 12 in a pivoted fashion by the holder 32 . Except for the supply line 30 , no other hydraulic fluid connections are provided.
[0023] The damping device 48 is constructed in the form of a simple helical compression spring that is situated in the piston rod chamber of the cylinder housing 66 between the piston 68 and the plate 72 and surrounds the piston rod 70 with a certain amount of play. An annular disc 74 is arranged on the damping device 48 , namely on its side that faces the piston 68 . This annular disk 74 serves for achieving a superior contact between the damping device 48 and the piston 68 and contains a not-shown seal on its outer circumference which decelerates its movement along the inner wall of the cylinder housing 66 and thus prevents the damping device 48 from moving freely and developing undesirable noises. However, the annular disk 74 is not absolutely imperative for the function of the damping device 48 and can also be omitted.
[0024] FIGS. 3 - 6 respectively illustrate different operating states of the implement. Specifically, in FIG. 3, the state shown is that which occurs in the mowing mode, i.e., the motor operators 60 are retracted, the gas pressure reservoir 56 assumes a neutral position and the damping device 48 is not stressed. FIG. 4 shows the state in which the motor operators 60 are extended in order to raise the implement 10 into its transport position. The piston 68 contacts the damping device 48 such that its stroke is stopped. In FIG. 5, the situation shown is that which occurs when the implement 10 moves over an obstacle and the wheel suspension 16 is subjected to a shock that cannot be absorbed solely by the pneumatic tires of the wheels 14 . In this case, the gas cushion in the gas pressure reservoir 56 is compressed and the piston 68 is able to move into the cylinder housing 66 . Although this is not imperative, the stress on the damping device 48 can be relieved. The pressure in the motor operator 60 significantly increases above the system pressure. Once the obstacle has been passed over, the state becomes that shown in FIG. 6 wherein the motor operator 60 is once again extended while being subjected to a less intense stress because the wheel 14 in question does not contact the ground. Since the gas pressure reservoir 56 is now able to abruptly release and may even generate an internal vacuum, the piston 68 impacts on the damping device 48 and is decelerated. This damping prevents the plate 72 from being damaged.
[0025] Referring now to FIG. 7, there is shown a second embodiment of the invention. Specifically, there is shown a damping device 48 ′ that includes a reversing element 76 , a brace or strut 78 and the gas pressure reservoir 56 . This damping device 48 ′ does not require a separate damping element, but rather is able to utilize the gas pressure reservoir 56 due to the change in direction caused by the reversing element 76 . The motor operator 60 in this embodiment is also constructed in the form of a single-acting hydraulic cylinder, wherein the arrangement in this embodiment is chosen such that the end of the cylinder housing 66 is situated on the bottom and the piston rod 70 extends upward. However, this is not absolutely imperative for the invention. The bracket 32 is situated in the lower end region of the limb 26 in this embodiment. Although only one motor operator 60 and only one bracket 32 are illustrated, these components are actually provided on both sides.
[0026] The reversing element 76 is constructed in the form of an essentially L-shaped or V-shaped, pivoted arm with two limbs, with an end of one limb containing a bearing 80 connected to the piston rod 70 , with the second limb having an end containing a bearing 82 connected to an upper end of the brace 78 , and with a bearing 84 located in the reversing element 76 between the bearings 80 and 82 and connecting the reversing element 76 to a holder or bracket 86 constructed of a single member or parallel, fork-like members fixed to the undercarriage 12 or its limb 26 , respectively. If a straight line is drawn through the bearings 80 and 82 , the bearing 84 is always situated laterally of this straight line, namely on the side that faces the motor operator 60 .
[0027] The brace or strut 78 extends between a bearing 88 on the bracket 46 in the upper rear region of the wheel suspension 16 and the bearing 82 on the reversing element 76 . The brace 78 may even be provided with a spring in order to additionally dampen shocks.
[0028] The function of the embodiment shown in FIG. 7 is as follows. Specifically, the undercarriage 12 is supported on the ground by the wheels 14 , wherein an essentially rigid connection that contains the motor operator 60 arranged in a pivoted fashion on the limb 26 , the reversing element 76 , the brace or strut 78 and the wheel suspension 16 counteracts a downward movement of the undercarriage.
[0029] Leaving aside the elasticity that is inherent to each component, only the gas pressure reservoir 56 performs a spring function. This means that the gas cushion of the gas pressure reservoir 56 is more or less compressed when the wheels 14 move over a rock or similar uneven terrain or obstacle. In such instances, the wheel suspension 16 , according to FIG. 7, is pivoted in the counterclockwise direction, the strut 78 is raised and the reversing element 76 is also pivoted about the bearing 84 in the counterclockwise direction. Due to this pivoting movement, the piston rod 70 presses into the cylinder housing 66 and compresses the gas cushion in the gas pressure reservoir 56 .
[0030] As soon as the obstacle is passed over and the force acting upon wheel suspension 16 decreases such that the gas pressure reservoir 56 is able to release, the compressed gas extends the piston rod 70 and the reversing element 76 is pivoted in the clockwise direction until the central longitudinal axis of the piston rod 70 and a line drawn through the bearings 80 , 84 are situated congruently or in alignment with each other. In this case, the piston 68 has not yet reached the plate 72 but is also prevented from additionally extending by being located on center with the pivot points established by the bearings 80 and 84 . If the wheel 14 and the wheel suspension 16 are able to additionally pivot in the clockwise direction, e.g., because the wheel 14 “hangs in the air”, the piston rod 70 with the bearing 80 is moved over center relative to the bearing 84 and now causes the piston rod 70 to be pressed inward against the pressure in the gas reservoir 56 . This means that an additional downward movement is counteracted by a spring action. The distance of the bearing 80 from the bearings 82 and 84 can be chosen differently in order to vary the power transmitting ratio.
[0031] 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 towed implement is provided with ground support wheels mounted to its chassis by trailing wheel support arms and respective suspensions including lift cylinders with which are associated damping devices that operate in such a way as to prevent damage to a respective cylinder from rebounding forces resulting when the suspension is being returned to its operating position by the release of energy stored in spring arrangements of the suspension after being loaded by an obstacle engaging the associated wheel. In one embodiment, the spring arrangement includes a damping spring located between an end of the associated cylinder and piston, and in another embodiment, the spring arrangement includes a gas pressure reservoir which, by virtue the operation of a reversing link in the suspension, is loaded both when the wheel is caused to move in a first direction by engaging an obstacle, and when the wheel is moved in the opposite direction by the airborne wheel once past the obstacle. | 1 |
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation-in-part of patent application Ser. No. 10/428,276 for METHOD AND APPARATUS FOR BLENDING LIQUIDS AND SOLIDS INCLUDING NOVEL AND IMPROVED IMPELLER ASSEMBLY by Jorge O. Arribau and Michael G. Dubic, incorporated by reference herein.
BACKGROUND AND FIELD OF INVENTION
[0002] This invention relates to blenders as well as pumping apparatus; and more particularly relates to a novel and improved method and apparatus for blending liquids with solid particulate materials, and still further relates to a novel and improved impeller assembly which is conformable for use with blenders as well as centrifugal pumps.
[0003] Numerous types of blenders have been devised for intermixing and pumping large volumes of liquid/solid slurries. For example, downhole operations in oil and gas fields, such as, fracturing and cementing operations utilize a blender in which liquids and solids are introduced into a housing, a rotor within the housing, upper and lower impeller portions for intermixing the materials and throwing or advancing the materials outwardly into an annulus surrounding the rotor from which the resultant intermixture or slurry can be discharged into the well. A representative blender is that set forth and described in U.S. Pat. No. 5,904,419 to Jorge O. Arribau, one of the inventors of this invention which patent is incorporated by reference herein (hereinafter referred to as the '419 patent). Other representative patents are U.S. Pat. No. 4,239,396 to Arribau; U.S. Pat. Nos. 3,256,181 and 3,326,536 to Zingg; U.S. Pat. No. 4,850,702 to Arribau and U.S. Pat. No. 4,460,276 to Arribau.
[0004] In the '419 patent, liquids were introduced through mixing apertures intermediately between the rotor and annulus for mixing with the solid particles prior to introduction into the relatively high pressure annulus.
[0005] There is a continuing but unmet need for a blender of simplified construction which can regulate the balance or mixing point between the solids and slurry in a region radially inwardly of the annulus and be capable of pumping the slurry under a substantially constant pressure over a wide range of mass flow rates. There is similarly a need for an impeller assembly in which impeller vanes are designed to regulate the slurry pressure as well as to prevent liquid or slurry leakage back into the central expeller area. Still further, to decrease the depth of vanes required for the upper impeller region by encouraging more immediate outward flow of sand to achieve the same capacity or mass flow rate as deeper vanes.
SUMMARY OF THE INVENTION
[0006] It is therefore an object of the present invention to provide for a novel and improved method and apparatus for blending liquids and solid particles by counterflow of the liquid with respect to the direction of solid flow through an impeller region.
[0007] It is another object of the present invention to establish a balance point between liquid and solid particle intermixture in an impeller for a blender and to control the pressure and velocity of liquid/solid flow by regulating the size, length and configuration of the impeller vanes.
[0008] It is a further object of the present invention to prevent backflow of liquids or solid particles around impeller zones of a blender apparatus.
[0009] It is a still further object of the present invention to provide in a pumping system for an impeller design capable of maintaining substantially constant pressure of a liquid/solid slurry over a wide range of mass flow rates.
[0010] In accordance with the present invention, there is provided in apparatus for blending liquids with solid particles in which a housing has an upper solid particle inlet and lower liquid inlet, a center drive shaft in said housing and outlet communicating with an annular space in outer spaced surrounding relation to the drive shaft, the invention characterized by having upper impeller vane means mounted for rotation on the shaft whereby to direct solid particles from the inlet toward the annular space, lower impeller vane means mounted for rotation on the drive shaft whereby to direct liquid from the liquid inlet through the annular space to intermix by counterflow of the liquid with the solid particles, and a plate interposed between the upper and lower impeller vane means. In the preferred form, the upper impeller means includes inner and outer concentric vanes, the inner vanes being operative to force the solid particles into the outer impeller vane region at a rate sufficient to substantially reduce the height of the outer vanes necessary to intermix the desired ratio of solid particles to liquids and prevent any tendency of the solid particles to back up into the center inlet region. In another preferred form of invention, the radial tips of the upper impeller vanes are lengthened to discourage return flow of the liquids or slurries toward the center of the impeller region.
[0011] The above and other objects, advantages and features of the present invention will become more readily appreciated and understood from the following description of preferred and modified forms of invention when taken together with the accompanying drawings in which:
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] [0012]FIG. 1 is a longitudinal section view of a preferred form of invention taken vertically through the apparatus.
[0013] [0013]FIG. 2 is a top plan view partially in section of the preferred form of invention shown in FIG. 1;
[0014] [0014]FIG. 3 is a view in detail of inner concentric impeller vanes employed on the upper impeller of the invention;
[0015] [0015]FIG. 4 is a cross-sectional view taken about lines 4 - 4 of FIG. 1;
[0016] [0016]FIG. 5 is a somewhat perspective view of the impeller vanes illustrated in FIG. 3;
[0017] [0017]FIG. 6 is a fragmentary side elevational view of the preferred form of invention mounted on a truck;
[0018] [0018]FIG. 7 is a longitudinal section view of a modified form of invention;
[0019] [0019]FIG. 8 is a cross-sectional view taken about lines 8 - 8 of FIG. 7;
[0020] [0020]FIG. 9 is a sectional view taken about lines 9 - 9 of FIG. 7;
[0021] [0021]FIG. 10 is a fragmentary view of another preferred form of invention illustrating modifications to the vanes of the impeller assembly; and
[0022] [0022]FIG. 11 is a cross-sectional view taken about lines 11 - 11 of FIG. 10.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0023] Referring in more detail to the drawings, a preferred form of blender apparatus is illustrated in FIGS. 1 to 5 , and FIG. 6 illustrates a typical mounting of a blender apparatus on a truck T whether the apparatus be of the preferred form of blender apparatus 10 illustrated in FIGS. 1 to 5 or the modified form of apparatus 10 ′ illustrated in FIGS. 7 to 9 . In oil and gas operations, such as, fracturing or cementing wells, the apparatus 10 or 10 ′ is mounted on a truck bed B including an engine E with a drive mechanism D to impart rotation via speed reducer mechanism M to a central drive shaft 12 . The solid particulate matter, such as, sand is delivered from a storage area S by means of an auger system represented at A to the upper end of a hopper 14 . There, the sand is permitted to advance by gravity into the apparatus 10 or 10 ′. The sand is thoroughly mixed with a liquid which is introduced through an inlet line L 2 into the inlet port 16 ; and the resultant slurry is discharged via outlet port 18 through a delivery line L 1 with sufficient pressure to be delivered to other trucks for delivery to a well head. The speed reducer M is a right angle drive as shown to enable the blender apparatus 10 to be oriented vertically in order to receive the sand and other dry chemicals under gravity flow through the hopper 14 . The sand screw assembly or auger A has the capability of introducing sand from the storage area S to a point at least 10″ above the inlet of the hopper 14 so that the mass flow rate of sand downwardly through the hopper is sufficient to produce the desired flow rate of sand through the discharge port. While the apparatus is described and shown as being truck-mounted, it will be appreciated that it can be as readily mounted on a fixed support and be oriented vertically or canted at an angle, such as, in the manner disclosed in hereinbefore referred to U.S. Pat. No. 5,904,419.
[0024] The apparatus 10 of the preferred form of invention is illustrated in more detail in FIGS. 1 to 5 and will be seen to be broadly comprised of a base mount 20 including a bearing to support the lower end of the drive shaft in journaled relation to the mount, a cylindrical wall or casing 22 extending upwardly from the base mount 20 into an enlarged housing area 24 for the speed reducer mechanism M, and an intermediate casing 26 includes a bearing 27 to which an intermediate portion of the drive shaft 12 is journaled. The upper end of the casing 26 terminates in a flange 28 which is attached by suitable fasteners 29 to a substantially flat underside 30 of an upper impeller housing 32 for an impeller assembly generally designated at 34 within the housing 32 . The underside 30 is of annular configuration and disposed in outer spaced concentric relation to the drive shaft 12 , the impeller assembly 34 being mounted for rotation on the drive shaft in a manner to be described.
[0025] The impeller housing 32 has a substantially flat top side 36 of annular configuration parallel to the underside 30 and joined to the underside 30 by an outer continuous wall 38 of generally convex or toroidal cross-sectional configuration. The hopper 14 converges downwardly through a central opening in the top side 36 and is centered with respect to the drive shaft 12 . An upper flat, annular connecting plate 40 is attached by suitable fasteners to the top side 36 and has an inner thickened ring-like portion 42 attached by suitable fasteners to the top side 36 and wedged against a necked down portion 44 of the hopper 14 . A butterfly valve 48 with suitable hand control arm 49 is mounted in the hopper to seal off the mixer when desired and can assist in regulating the flow rate of sand into the impeller housing 32 . The discharge port 18 extends tangentially away from the outer wall 38 of the housing 32 , and the inlet port 16 extends radially into the housing 26 immediately below the expeller housing 32 .
[0026] An important feature of the present invention resides in the impeller assembly 34 which is comprised of upper impeller vanes 50 and lower impeller vanes 52 interconnected by a common plate 54 which is centered for rotation on the upper end of the drive shaft 12 by means of a cup-shaped retainer 56 . The upper impeller vanes 50 are bounded by a cover plate 58 having radially extending, circumferentially spaced expeller vanes 60 . The plate 58 is of annular configuration and mounted in surrounding relation to the lower edge 44 of the hopper 14 . The top side 36 of the housing 32 has a downwardly projecting, circular rib 62 extending into a circular slot 64 in the cover plate 58 as well as the vanes 60 , as best seen from FIGS. 1 and 2. The rib or baffle plate or deflector 62 cooperates with the expeller vanes 60 in minimizing any return flow of slurry or liquids toward the center region of the impeller.
[0027] The lower vanes 52 are similarly bounded by a bottom cover plate 66 having spaced expeller vanes 68 to discourage return flow of slurry or liquids around the underside of the housing. A rib 30 ′ projects upwardly from the underside 30 of the housing 32 radially inwardly of the inner terminal edges of the plate 66 and vane 68 to cooperate in discouraging the return flow of slurry or liquids.
[0028] The upper vanes 50 are shown in detail in FIG. 4, each having an inner edge or tip 70 substantially tangent to the inner radial edge of the cover plate 58 and curving radially and outwardly in a trailing direction to define a generally arcuate or concavo convex curvature at 71 , then turning in a radial direction to terminate in outer tips 72 which are perpendicular to the direction of flow. The direction of curvature of the upper vanes 50 presupposes that the vanes are rotating in a clockwise direction when viewed upwardly. The vanes diverge gradually outwardly from one another and terminate in the tips 72 at the edge of the common plate 54 but inwardly of the outer edge of the cover plate 58 .
[0029] As further illustrated in FIGS. 3 to 5 , a plurality of expeller blades 80 are mounted on a base plate 81 which is affixed to the plate 54 at the eye of the impeller. The blades are keyed to the drive shaft 12 by a central fastener 82 threaded onto upper end portion of the shaft 12 . Each of the blades 80 includes a flat radial portion 84 extending vertically and upwardly from the plate 81 and terminates in an upper curved or rounded portion 85 having a top machined or flattened surface 86 . Preferably, the blades 80 correspond in number and spacing to the vanes 50 and are oriented or aligned with the entrances between the tips 70 of adjacent vanes 50 so as to redirect the incoming sand from the hopper 14 in a radial direction into the upper passages between the impeller vanes 50 . The upper curved ends 85 are curved in the direction of rotation of the shaft 12 so as to confine the flow of the sand in an outward radial direction.
[0030] The lower vanes 52 , as shown in FIG. 9, are of the same configuration as the upper vanes 50 including inner somewhat tangential tips 74 , arcuate portions 75 and outer radial tips 76 which also terminate at the outer edge of the common plate 54 and are rotating at the same rpm but will oppose the entrance of liquid into the upper impeller region. Nevertheless, the liquid is under sufficient pressure to undergo counterflow into the upper impeller region until it reaches a balanced pressure condition with the sand being driven outwardly between the upper impeller vanes 50 . As the upper vanes 50 approach the discharge port 18 the sand/water slurry will be driven outwardly under sufficient force by the vanes 50 as to overcome the counterflowing liquid and be discharged to the well head. The balance point or condition established between the sand and slurry is regulated to some extent by the relative length of the vanes 50 and 52 . For example, as illustrated in FIGS. 4 and 9 , the upper vanes 50 are substantially longer than the lower vanes 52 and in cooperation with the expeller blades 80 of sufficient velocity while maintaining the necessary high pressure condition to overcome the water pressure and be discharged through the port 18 . Further, the combined use of the expeller blades 80 with the longer impeller vanes 50 will create greater pressure to push the water back at a balance point beyond the midpoint of the upper impeller vanes 50 ; and at the same time the height of the upper vanes 50 may be reduced to obtain the same capacity or mass rate of flow as substantially higher vanes, for example, as shown and described in the modified form of FIGS. 7 to 9 . Maintaining the balance point at least beyond the midpoint of the upper vanes will help also to discourage leakage of water past the sand into the central inlet or eye of the impeller 34 .
[0031] The following working example is given for the purpose of illustration in the utilization of the blender method and apparatus of the preferred form of invention in mixing sand and water and delivering continuously to a well head: The inlet end of the impeller at the lower reduced end 44 of the hopper 14 is 12″ less the diameter of the center fastener 82 for the expeller blades 80 , and the sand is delivered at a constant rate through the auger A to a point no less than 10″ above the inlet in order to reach the design criteria of 30,000 lbs. of sand per minute through the opening. Again, in order to reach the design criteria of 30,000 lbs. of sand per minute through the outlet 18 , the expeller blades 80 and impeller vanes 50 and 52 are greater than 0.62″ in depth and are rotated at 1050 rpm. The water will enter the blender apparatus 10 through a 10″ to 12″ diameter inlet 16 and will not be accelerated until it reaches the vanes 52 whose inner tips are at a radius of 9″. The water is accelerated by the vanes 52 until it reaches the outer tips of the vanes at a radius of 14″ whereupon the liquid is driven into the annulus and energized to a pressure of approximately 100 psi. The liquid will then occupy the entire annulus and begin to invade the upper set of impeller vanes 50 which are rotating at the same rpm as the lower vanes and therefore opposing the entrance of the liquid into the upper section of the impeller. Once the liquid has reached a point 9″ from the center of the upper vanes 50 it will have dissipated its energy somewhat, and any tendency of the liquid to reach the eye of the impeller will be overcome by the length of the upper vanes 50 which will be on the order of 8″ compared to the lower vanes which are on the order of 5″. Accordingly, the eye of the upper impeller will be free of liquid so as not to interfere with the introduction of the sand from the auger A.
[0032] The expeller blades 80 will impart a velocity on the order of 660″ per second as a result of which it is not necessary to have a higher depth of sand expeller vane 50 than the depth of the lower water vanes 52 . Thus, the depth of the upper vanes 50 may be more on the order of 0.6″ to 1.0″ and therefore considerably more compact for the mass rate of flow of sand being handled. In addition, the expeller blades 80 reduce the area of the vanes which must be exposed to the pressurized liquid and therefore reduces the torque required to maintain the requisite rpm and correspondingly reduces the horsepower required on the engine. It will be evident that the size of the inlet may be reduced depending upon the amount or capacity of sand and water being discharged and therefore minimize the net positive suction head required.
[0033] Another preferred form of invention is illustrated in FIGS. 10 and 11 in which like parts are correspondingly enumerated. Specifically, the upper vanes 50 ″ have the same configuration as the vanes 50 and 50 ′ of the preferred and modified forms hereinbefore described, but outer radial tips 72 ″ are lengthened to extend to the outer peripheral edge of the common plate 54 in order to most effectively discourage the return flow of slurry or liquids toward the expeller blades 80 .
DETAILED DESCRIPTION OF MODIFIED FORM OF INVENTION
[0034] FIGS. 7 to 9 illustrate a modified form of blender apparatus 10 ′ in which like parts are correspondingly enumerated with prime numerals. As shown in FIGS. 8 and 9, the vanes 50 ′ and 52 ′ are separated by a common plate 54 ′ and are of corresponding configuration to the vanes 50 and 52 of the preferred form of invention. However, the upper vanes 50 ′ are substantially increased in depth to compensate for the absence of the expeller blades 80 rapidly discharging the sand from the eye into the impeller vanes 50 ′. Thus, as represented, the increased depth of the inlet area beneath the hopper 14 ′ as well as the increased depth and size of the upper impeller occupied by the vanes 50 ′ may be varied and will enable greater amounts of sand to be introduced but at a much lower rate of flow. Furthermore, referring to the working example given with respect to FIGS. 1 to 5 , in order to move a corresponding amount of sand would require an impeller vane 50 ′ of a depth six to eight times greater than that of the preferred form. Nevertheless, the modified form of invention is similarly capable of delivering the mixture or slurry under the same pressure over a wide range of mass flow rates.
[0035] The vane configuration devised for the preferred and modified forms of invention enable close control over the pressure of the solid and liquid materials in order to achieve optimum performance. For example, when the vanes are curved in the same direction as the direction of rotation, the pressure increases as the rate of flow of the materials increases and, in curving away from the direction of rotation, the pressure will decrease. However, any tendency to decrease can be overcome by adding the straight radial portions 72 or 76 to the radially outer ends of the vanes. FIGS. 10 and 11 illustrate the lengthening of the blade tips 72 ″ to be flush with the outer edges of the plate 54 . As seen from FIGS. 4 and 9, the degree of curvature of the portions 71 and 75 as well as the relative length of the tips 72 and 76 can be varied to achieve different flow and pressure characteristics for a given rpm or speed of rotation of the vanes. It is therefore to be appreciated that the preferred and modified forms of invention are readily conformable for use in mixing various solids and liquids. It will be further evident that the vane configuration of the impeller vanes 50 and 52 is conformable for use in numerous applications other than blender apparatus and for example are adaptable for use in centrifugal pumps or in virtually any application where it is desirable to control the pressure of liquid or solid particles by regulating the curvature of the impeller vanes.
[0036] It is therefore to be understood that while preferred and modified forms of invention have been herein set forth and described, various modifications and changes may be made therein without departing from the spirit and scope of the present invention as defined by the appended claims. | An impeller vane assembly for blending liquids with solid particulate matter in which a center drive shaft extends through a housing having a solid particle inlet and a liquid inlet together with an outlet, and upper and lower impeller vanes are aligned respectively with the particle inlet and liquid inlet to cause intermixing of the solids and liquids by counterflow of the liquid into the upper impeller region, the upper and lower vanes being separated by a common divider plate, and the vanes are characterized by being curved in the direction of rotation of the impeller and having outer radially extending tips which terminate at the outer peripheral edge of the common divider plate, the vanes being operative to balance the point at which the solids and liquid are intermixed between the solid particle inlet and annular space surrounding the impeller. In one embodiment, expeller blades are employed in inner concentric relation to the upper impeller vanes to accelerate the flow of solid particles into the upper impeller region, and baffle plates or deflector members are employed above and below the upper and lower impellers to prevent any leakage of liquid into the center of the impeller. In preferred and alternate forms, the impeller vanes are sized to balance the point at which the solids and liquid are intermixed. | 1 |
CROSS REFERENCE TO RELATED APPLICATIONS
This application is a continuation of U.S. application Ser. No. 10/211,748 filed Aug. 2, 2002, and now abandoned, which is a continuation of International Application PCT/US00/02907 with an international filing date of Feb. 4, 2000.
FIELD OF THE INVENTION
The present invention relates to air deodorizing devices for removing malodor from the air. Such devices are useful for example for storing and preserving food in closed compartments such as refrigerators.
BACKGROUND
Nowadays, refrigerators have become a common appliance in virtually every household and typically are used for storage and preservation of food, in particular of fresh food such as fruits, vegetables, dairy products, and the like. It is desirable to keep the food items fresh as long as possible in the refrigerator.
It is a well known problem that many food items tend to release malodors into the air which are then captured in the limited air space in a refrigerator. Not only are these malodors unpleasant and offensive to the user of the refrigerator, they can also have a negative impact on the quality of other foods in the refrigerator. For example, it is known that some foods emit strong odors (e.g. fish, boiled eggs, onions, etc.) and that,these odors can transfer to other nearby foods and hurt the taste and freshness of those foods. A common example is transfer of odors into an open container of orange juice or of milk resulting in a noticeable degradation in their taste. It is also well known that malodors from some vegetables (onions, garlic) can transfer to other foods stored within a vegetable drawer. This problem is aggravated when the vegetable drawer is sealed such that there is very little air exchange with the larger compartment of the refrigerator (herein referred to as the “fresh food compartment”) and when vegetables have been cut or are stored without any outer wrapping. This problem of odor transfer is particularly acute in the case of ice cubes where odors from the fresh food compartment of the refrigerator can be transferred to the ice in the freezer compartment of the refrigerator. This is especially true in the case of refrigerators in which there is air exchange between the fresh food and freezer compartments, and especially in the case of refrigerators with built-in ice-makers.
U.S. Pat. No. 5,403,548 discloses an activated carbon absorbent to be used for example in refrigerators, shoe boxes, closets, toilets, cars, cupboard, or the like. The activated carbon absorbent is applied in a gas treating apparatus comprising an air inlet, an air outlet, a cylinder housing the activated carbon honeycomb, and a fan aspiring malodor through the air inlet. Change of battery and withdrawal of the cylinder housing the activated carbon are achieved by dismounting the cover of the apparatus. The gas treating apparatus may further comprise an action member for alerting the user to the event that the useful life of the activated carbon adsorbent has run out. This gas treating apparatus has the disadvantages that exchange of batteries and withdrawal of the activated carbon require a multitude of steps including dismounting of the cover and that exchange of battery and activated carbon are carried out separate from each other.
It is therefore an object of the present invention to provide an air deodorizing device which overcomes the disadvantages of the prior art devices.
It is a further object of the present invention to provide an air deodorizing device comprising a replaceable cartridge member housing a filter member whereby the cartridge member is directly accessible from the outside.
It is a further object of the present invention to provide an air deodorizing device comprising a cartridge member housing a replaceable filter member whereby the cartridge member is directly accessible from the outside.
It is a further object of the present invention to provide an air deodorizing device comprising a replacement cartridge member housing a power supply and a filter member.
It is a further object of the present invention to provide an air deodorizing device having a replaceable power supply and a replaceable filter member, the lifetimes of the power supply and the filter member being of the same magnitude.
SUMMARY OF THE INVENTION
The present invention provides an air deodorizing device comprising a cartridge member, the air deodorizing device having an air flow path from an air inlet to an air outlet. The cartridge member comprises a filter member and is arranged with the filter element in interaction with the air flowing along the air flow path. The air deodorizing device further comprises an air moving member for moving air along the air flow path, and is characterized in that the cartridge member is detachable from the air deodorizing device.
DETAILED DESCRIPTION OF THE INVENTION
The device of the present invention is intended to deodorize air, in particular air in confined compartments such as refrigerators, trash bins, cars, closets, and the like.
The cartridge member of the present invention housing the filter member is detachable from the device. The term “detachable” as used herein refers to members which can be easily removed, in particular where no tools such as screw drivers are needed. Preferably, no excessive forces are need for detaching the cartridge means, the cartridge means is directly accessible from the outside, and the cartridge member can be removed by holding the device of the present invention in one hand and by removing the cartridge member with the other hand.
Deodorization of the air in the device of the present invention is achieved by adsorbing the molecules constituting a malodor onto a surface of a filter member. The term “adsorption” is well defined in the art and refers to the adherence of molecules to surfaces which effectively reduces the mobility of these molecules to the two dimensions of the surface. Those molecules remaining in the air will then diffuse so that further molecules come into contact with the surface and subsequently will be adsorbed. Consequently, most of the malodor molecules will travel into the proximity of one of the surfaces at some point in time so that finally most of the malodor will be removed from the air.
A suitable filter member comprises activated carbon for the adsorption. Activated carbon is known to be a very effective filter medium due to its high specific surface area. Whilst activated carbon is very effective as such, the filter member of the present invention may further comprise agents supported on the activated carbon to specifically attack certain malodors such as those comprising S atoms or N atoms. A wide variety of activated carbon based filter media is known in the art. Preferably, the filter members of the present invention comprise at least 2 grams, more preferably at least 5 grams, and most preferably at least 10 grams of activated carbon. Preferably, the filter members of the present invention comprise less than 100 grams, more preferably less than 50 grams, yet more preferably less than 40 grams, and most preferably less than 30 grams of activated carbon.
The filter member of the present invention comprises an air inlet, an air outlet, and an air flow path through the filter member from the air inlet to the air outlet. The filter medium is disposed in the filter member of the present invention such that it comes into contact with the air flowing along the air flow path. The filter medium may be arranged as a flow by filter or as a flow through filter. The filter member of the present invention may comprise a support for the filter medium for example in the form of a foam, a nonwoven material or a woven material. Preferably, the activated carbon is supported on a polyurethane foam having an activated carbon density of at least 0.01 grams per cm 3 , more preferably of at least 0.05 grams per cm 3 , and most preferably of at least 0.1 grams per cm 3 and having an activated carbon density of less than 0.3 grams per cm 3 .
The deodorization of the air in the device of the present invention is enhanced by increasing the air flow through the filter member by means of an air moving member. Preferably, the air moving means moves at least 100 ml of air per second through the air inlet into the device, more preferably at least 200 ml/s, most preferably at least 300 ml/s. There are known in the art a wide variety of suitable air moving members such as for example fans and blowers. A particularly suitable fan is a centrifugal fan. A suitable member for driving the fan is a small motor, for example a DC motor available from MABUCHI MOTOR CO.,LTD., Japan, under the designation of RF-330TK. The air moving members of the present invention may be powered electrically. Many electrical power sources could be imagined including domestic AC electrical power or power from a static power supply. Alternatively and preferably electrical power may be supplied by means of a battery, preferably a dry alkaline cell battery, or a rechargeable battery. The electrical power may also be received from a solar cell. Any replaceable power supply preferably is designed to last at least one month, more preferably at least two months, yet more preferably at least three months, most preferably at least four months.
To improve the malodor removal performance and to simplify the mechanical construction of the air deodorizing device of the present invention, the filter member and the air moving member are preferably arranged such that substantially all air aspired by the air moving member is forced to flow through the filter member before it penetrates the air inlet of the air moving member. In other words, the air inlet of the cartridge member is unitary with the air inlet of the air deodorizing device. In this setup, only one air path connection is needed between the filter member and the air member and hence complexity is decreased. Furthermore, withdrawal of the cartridge member is greatly simplified if only one connection has to be disengaged. Any disengageable air flow connection may of course comprise sealing members to improve air flow performance. Any such connection may further comprise a mechanical engaging members to stabilize the connection.
The filter member of the present invention may be replaced by detaching the cartridge member from the device of the present invention and inserting in a new one. It is to be understood in this context that the present invention includes embodiments in which the cartridge member as a whole comprising a filter member is replaced and further includes embodiments in which the cartridge is reused and contains a replaceable filter element.
Preferably, the cartridge member of the present invention is directly accessible from the outside of the device without the need to unmount any covers or the like. More preferably, the cartridge member can simply be lifted off from the device. For example, the cartridge member may simply be sitting on top of the air moving member only held in place by gravitational forces whereby the surface topology of the interfacing parts of the cartridge member and the air moving member match each other such as in a hemispherical design.
Optionally, the cartridge member of the present invention may further comprise the power supply for the air moving member. In this case, the interface between the cartridge member and the air moving member needs to comprise electrical contacts connecting the power supply with the drive member of the air moving member.
Preferably, the lifetime of the filter member and the lifetime of the power supply are substantially equal so that both members may be replaced at the same time intervals. In this case, an empty power supply would also signal that the filter element has to be replaced.
The air deodorizing device of the present invention may comprise a signal member to indicate if the life span of the filter member has run out. The signal member may be slaved to the time the filter member has been exposed to air or may be slaved to the overall runtime of the air moving member. In case the power supply for the air moving member is included in the filter member and accordingly is replaced with the filter member, the signal member may be slaved to the remaining charge of the power supply thus indicating that filter member and power supply needs to be replaced. | The present invention relates to air deodorizing devices for removing malodor from the air. Such devices are useful for example for storing and preserving food in closed compartments such as refrigerators. The air deodorizing device of the present invention comprises a cartridge member and an air moving member whereby the cartridge member is detachable from the device. | 0 |
ORIGIN OF THE INVENTION
The invention described herein was made in the performance of work under a NASA contract and is subject to the provisions of Section 305 of the National Aeronautics and Space Act of 1958, Public Law 85-568 (72 Stat. 435; 42 U.S.C. 2457).
This is a division of application Ser. No. 739,760, filed 5/31/85, which is a continuation of Ser. No. 561,702, 12/15/83, abandoned.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to novel aromatic amine terminated bisaspartimides which are useful as precursors for preparing novel, cross-linked, high temperature stable polymeric resins, and to a method for making the bisaspartimides. More particularly, the invention relates to novel 4,4'-bis{N 2 -[4-(4-aminophenoxy)phenyl]aspartimido}diphenylmethane, which may be thermally polymerized to produce a tough polymer. If further relates to a process for preparing these bisaspartimide compounds by a Michael-type reaction of an aromatic bismaleimide and an aromatic diamine in an aprotic solvent. It also relates to novel cloth laminates incorporating the polymers of this invention.
2. Description of the Prior Art
High temperature resistant polymers are used extensively in advanced aerospace structures in which structural integrity must be retained during continuous use at temperatures of 325 degrees C. and above. The stringent requirements of space technology and of other industrial applications for thermal protective materials have led to the development of several classes of heat- and flame-resistant heterocyclic polymers. Aromatic polyimides, developed during the 1960s, have met these requirements to a large extent. They are prepared by a condensation reaction. Loss of desirable mechanical properties and problems of reproducibility have been observed because of voids created by the elimination of water during their formation in situ, difficulty in the removal of high boiling point solvents, or both. As a result, the use of these polyimides as laminating resins or for adhesives has been limited. Such polyimides are disclosed, for example, in the following references: C. E. Sroog, J. Polym. Sci., 16, 1191 (1967); M. L. Wallach, J. Polym. Sci. A-2, 5, 653 (1967); R. Ikeda, J. Polym. Sci., B, 4, 353 (1966); C. E. Sroog, A. L. Endrey, S. V. Abramo, C. E. Bear, W. M. Edwards, and K. L. Oliver, J. Polym. Sci. A, 3, 1373 (1965); R. A. Dine-Hart and W. W. Wright, J. Appl. Polym. Sci., 11, 609 (1967).
Initial attempts to overcome these processability problems led to the development of addition polyimides based on short, preimidized segments which polymerize thermally through end groups without loss of volatiles, such as disclosed by F. Grundschober and J. Sambeth, U.S. Pat. Nos. 3,380,964; 3,523,996; French Pat. No. 1,455,514; Chem. Abstr., 65, 10746 (1966). However, these addition polyimides were found to be inherently brittle because of extensive cross-linking that occurs during polymerization.
P. Kovacic, U.S. Pat. No. 2,818,405; Chem. Abstr. 52, 5018e (1958), reported the reaction of amine capped liquid elastomeric prepolymers with bismaleimides to afford polymers. However, these elastomer based polymers were not heat resistant. M. Bargain et al, U.S. Pat. No. 3,562,223; Chem. Abstr. 72, 4047 (1970) disclose cross-linked resins obtained by the melt polymerization of bismaleimide and the addition of diamine to the melt in ratios of 1.2:1 to 50:1 with further polymerization. The prepolymers thus formed are used to prepare prepregs via their N-methylpyrrolidone solution to give laminates. However, these resins show a tendency to polymerize in solution, significantly increasing the solution viscosity and causing processing difficulties.
A wide variety of polyimide resins derived from bismaleimides and/or aromatic diamines, in combination with various other materials, are known in the art. Such resins are disclosed in, for example, the following U.S. Pat. Nos. 3,671,490; 3,740,378; 3,766,138; 3,855,239; 3,897,393; 4,020,303; 4,060,515; 4,075,171; 4,116,937; 4,280,946; 4,283,521; 4,316,843; 4,273,916; 4,346,206. See also J. V. Crivello, J. Polym. Sci., 11, 1185 (1973).
While the art pertaining to high temperature stable resins and precursors is a well developed one, there is a continuing need for a polyimide binder that can be used as a matrix for low void fiber reinforced composites that retain favorable properties and have thermooxidative stability. Such binders should also be capable of being used in rapid, high pressure, matched-die molding, as well as in lower pressure vacuum bag autoclave molding. It has not been found to be desirable to use a high molecular weight polymer in a solution as a binder because the solution is too viscous at a high solids content for handling. At low solids concentration, there is usually insufficient resin pick up in one pass in the prepregging operation.
Whereas other mixed bismaleimide-aromatic amine systems polymerize thermally by reaction of vinyl groups with either other vinyl groups or with free amino groups, depending on the stoichiometry of the system, the herein described materials, having all or substantially all their vinyl group previously prereacted with one amino group of an aromatic diamine, is believed to cure by an imide ring opening reaction to form amides. It is also known that an imide ring opening reaction occurs as a side reaction of an amino acid (proline) reacting with a substituted ester, as reported by J. Savrda, J. Org. Chem., 42, 3199 (1977).
SUMMARY OF THE INVENTION
A binder which meets these requirements is provided by the novel aromatic amine terminated bisaspartimides herein disclosed, which polymerize with cross-linking at moderate temperatures to provide rigid, tough, cured structures. The bisaspartimides of this invention have the formula: ##STR1## X in the above formula is a divalent organo radical, such as a hydrocarbon group containing from 1 to 4 carbon atoms, or other divalent radicals capable of linking two benzene rings, such as a --CH 2 -group a ##STR2## group, --O--, --S--, --CO-- or --SO 2 --. Y is a divalent organo radical, such as a hydrocarbon group containing from 1 to 4 carbon atoms, such as a --CH 2 -group, a ##STR3## group, or other divalent radicals capable of linking two benzene rings, such as --O-- or --S-- or --SO 2 -- or --CO-- or the like, and n is, independently in each case, an integer of 0 or 1.
The method for preparing an aromatic amine terminated bisaspartimide in accordance with this invention comprises reacting an aromatic diamine and an aromatic bismaleimide in a mol ratio of about 2:1 with an acid catalyst in an aprotic solvent. The method desirably employs an aromatic diamine having the formula: ##STR4## and an aromatic bismaleimide having the formula: ##STR5## In these formulas, X, Y and n have the meaning given previously. In an especially preferred embodiment, the acid catalyst is glacial acetic acid, the aprotic solvent is dimethylacetamide, and the reaction is carried out in an inert atmosphere, such as nitrogen.
The polymer prepared by thermally polymerizing the novel bisaspartimides of this invention is a cross-linked polymer having recurring structural units of the formula: ##STR6## in which X, Y and n have the meaning given previously. While applicants do not wish to be bound by any particular theory, it is believed that the cross-linked polymers of this invention are rigid and tough, rather than brittle as in the case of prior cross-linked polyimides, because larger structural units are available for internal molecular motion after cross-linking.
The attainment of the foregoing and related objects, advantages and features of the invention should be more readily apparent to those skilled in the art, after review of the following more detailed description of the invention.
DETAILED DESCRIPTION OF THE INVENTION
Suitable specific examples of aromatic bismaleimides for preparing the novel bisaspartimides of this invention include: 4,4'-bismaleimidodiphenylmethane; 4,4'-bismaleimidodiphenylether; 4,4'-bismaleimidobiphenyl; 4,4'-bismaleimidodiphenylsulfone; 4,4'-bismaleimidodiphenylthioether; 4,4'-bis-maleimidodiphenyldimethyl-silane; 1,4-phenylenebismaleimide; 1,3-phenylenebismaleimide and the like. These and similar bismaleimides may be prepared by the condensation of maleic anhydride with a required equivalent ratio of the corresponding aromatic diamines, in an acetone solvent, using the method disclosed by D. Kumar, Chem. Ind. London, 21, 189 (1981). Suitable specific examples of aromatic diamines that may be reacted with the above and similar bismaleimides to give the bisaspartimides of this invention include 4,4'-diaminodiphenylmethane; 4,4'-diaminodiphenylether; 4,4'-diaminodiphenyl sulphide; 4,4'-diaminodiphenylsulfone; 3,3'-diaminodiphenylsulfone; 4,4'-diaminobiphenyl; 4,4'-diaminodiphenyldimethylsilane; 4,4'-diaminodiphenyldiphenylsilane; 4,4'-diaminodiphenylpropane; benzidine; 4,4'-diaminophenoxyphenylene; 3,3'-diaminophenoxyphenylene; 2,2-bis(3-aminophenyl)hexafluoropropane; 3,2-bis(4-aminophenyl)hexafluoropropane.
In order to obtain amine terminated bisaspartimides in accordance with the above formula, it is important that a mol ratio of the aromatic diamine to bismaleimide of about 2:1 be employed. There is a competing reaction to produce a linear polyimide, which will occur at other mol ratios, as taught in U.S. Pat. No. 3,740,378.
Suitable specific examples of acid catalysts which may be employed in the practice of the process of this invention include, for example, organic carboxylic acids, such as acetic, propionic, chloroacetic, dichloroacetic, trichloroacetic, trifluoroacetic, cyanoacetic, formic acid, and the like; mineral acids, such as hydrochloric acid, hydrobromic acid, fluoroboric acid, and the like. These acid catalysts may be employed either singly or as mixtures. In many cases, they also serve as part of the solvent for the aromatic amines and bismaleimide reactants.
Suitable specific examples of aprotic solvents suitable for practice of the invention include benzonitrile, acetonitrile, dimethylacetamide, dimethylformamide, N-methylpyrrolidone, nitromethane, nitrobenzene, xylene, benzene, toluene, acetone, chloroform, methylene chloride, and the like. The organic solvents may be employed either singly or as mixtures.
In practice, the process of this invention is desirably carried out at an elevated temperature, such as refluxing temperature. For example, a temperature about 110 degrees to 120 degrees C. for six to seven hours will produce the desired polyimide precursor bispartimide compounds in good yield. Lower temperatures could be employed, but would require longer reaction times for comparable yields.
The following non-limiting examples describe preferred embodiments of the invention further, including a description of the high temperature resins obtained from polymerization of the novel bisaspartimides prepared in accordance with the novel process of this invention.
In the following examples, the reactions were carried out in a three-necked flask equipped with a nitrogen inlet and outlet. The reaction mixtures were stirred mechanically and heated in an oil bath. The reagents were added in the sequences and stoichiometries indicated below. The method described is that which gave the optimum yield of the compound in each case and does not represent the sole reaction conditions which produce the compounds in each case.
In the following examples the compounds listed in Table I below are utilized:
TABLE I______________________________________Compound Name______________________________________I 4,4'-diaminodiphenylmethaneII 4,4'-diaminodiphenyletherIII 4,4'-bismaleimidodiphenylmethaneIV 4,4'-bismaleimidodiphenyletherV 4,4'-bis{N.sub.2 --[4-4(-aminobenzyl)pheny1]- aspartimido}diphenylmethaneVI diacetylated derivative of compound V, used for polymer characterizationVII 4,4'-bis{N.sup.2 --[4-(4-aminophenoxy)asparti- mido}diphenyletherVIII diacetylated derivative of compound VIIIX 4,4'-bis{N.sup.2 --[4-(4-aminophenoxy)phenyl]- aspartimide}diphenylmethaneX 4,4'-bis{N.sup.2 --[4-(4-aminobenzyl)phenyl]- aspartimido}diphenyletherXI N--[4(4'-aminobenzyl)phenyl]- aspartimidobenzeneXII 4,4'-bis(N--phenyl)aspartimido]diphenylmethaneXIII polymer of compound IXXIV polymer of compound V______________________________________
EXAMPLE 1
The compound 4,4'-bis{N 2 -[4-(4-aminobenzyl)phenyl]aspartimido}diphenylmethane was prepared as follows: to a continuously stirred solution of 4,4'-diaminodiphenylmethane (I) (5.94 g, 0.03 mol) in dimethylacetamide (50 ml) under a nitrogen atmosphere, 4,4'-bismaleimidodiphenylmethane (III) (5.37 g, 0.015 mol) was added. To the resulting brown solution, glacial acetic acid (1-2 ml) was added and continuously stirred at 110 to 120 degrees for 6-7 hours, under nitrogen. After cooling, the solution was poured over crushed ice. The light brown solid obtained was filtered and washed with cold water. The brownish-yellow solid obtained after drying was macerated with dry warmed acetone. The soluble portion was filtered and concentrated. Addition of a few drops of petroleum ether to this cooled, viscous acetone solution gave a light yellow solid. The process of crystallization was repeated to give the desired compound (V) (7 g).
ANAL. for C 47 H 42 N 6 O 4 : C, 74.8%; H, 5.57%; N, 11.14%. Found: C, 74.5%; H, 5.3% N, 10.9%.
EXAMPLES 2-4
The procedure of Example 1 was repeated, utilizing the corresponding aromatic bismaleimides and aromatic diamines substituted for the aromatic bismaleimide and aromatic diamine used in Example 1 to give compound (VII), 4,4'-bis{N 2 -[4-(4-aminophenoxy)phenyl]aspartimido}diphenylether from II and IV; compound (IX), 4,4'-bis{N 2 -[4-(4-aminophenoxy)phenyl]aspartimido}-diphenylmethane from II and III; compound (X), 4,4'-bis{N 2 -[4-(4-aminobenzyl)phenyl]aspartimido}-diphenylether from I and IV. The results obtained and analysis of the resulting compounds are shown in Table II below.
TABLE II__________________________________________________________________________Preparation of (VII), (IX), and (X)Bismaleimide Diamine Amount Amount Microanalysis (%)Compound.sup.a Type (g) (mol) Type (g) (mol) C H N__________________________________________________________________________(VII) IV 5.40 0.015 II 6.00 0.03 Calcd: 69.47 4.73 11.05 Found: 69.20 4.40 10.60(IX) III 5.37 0.015 II 6.00 0.03 Calcd: 71.26 5.20 11.08 Found: 71.10 5.20 10.60(X) IV 5.40 0.015 I 5.94 0.03 Calcd: 73.02 5.29 11.11 Found: 72.60 5.10 10.80__________________________________________________________________________ .sup.a Compounds (VI) and (VIII), not listed above, were acetylated derivatives of (V) and (VII), respectively.
The identity of each compound was confirmed by NMR and IR spectroscopy. The presence of amino terminals in bisaspartimides is confirmed by their reaction with nadic anhydride, pyromellitic anhydride and acetic anhydride, respectively.
EXAMPLE 5
The compound N-[4-(4'-aminobenzyl)phenyl]aspartimidobenzene, compound (XI), was prepared as follows: to a vigorously stirred solution of 4,4'-diaminodiphenylmethane (29.7 g, 0.15 mol) in dimethylacetamide (200 ml) in a nitrogen atmosphere, N-phenylmaleimide (26.0 g, 0.15 mol) was added. To the resulting brown solution, glacial acetic acid (1-2 ml) was added and the reaction was heated with stirring at 110-120 degrees C. for 6-7 hours. On cooling, the reaction solution was poured over crushed ice. The light yellow solid obtained was filtered, washed with water, and dried (yield 40 g). Repeated crystallization of the yellow solid from methanol-acetone did not give a pure compound. Thin layer chromatography examination of the resulting product showed two spots different from the starting compounds. Preparative TLC was used for the separation of these two compounds. The lower major spot was characterized as the required compound, which was confirmed by NMR and infrared spectroscopy. The other spot was identified by NMR and IR spectroscopy as the compound 4,4'-bis[(N-phenyl)-aspartimido]-diphenylmethane, compound (XII).
EXAMPLE 6
Compounds (V), (VII), (IX) and (X) were tested for their melting points in a capillary tube, and did not show any sharp melting points. The curing behavior of compounds (V), (VII), (IX) and (X) was determined by differential scanning calorimetry (DSC) in nitrogen. The temperature of first energy release T i (start of polymerization), the exothermic peak position T max , and the temperature of termination of polymerization T f were determined from the DSC trace for compound (VII), and are presented below in Table III.
TABLE III______________________________________Characteristic DSC Temperatures for Bisaspartimide (VII)Sample T.sub.i (°C.) T.sub.max (°C.) T.sub.f (°C.)______________________________________(VII) 145 157,175 230______________________________________
EXAMPLE 7
Compounds (V), (VII), (IX) and (X) were polymerized to give tough transparent brown polymers. The relative thermal stability of the compound (IX) and (V) polymers (XIII) and (XIV) was investigated by dynamic thermogravometry in air and nitrogen atmospheres. These resins were stable in air and nitrogen atmospheres up to about 370 degrees C., but started losing weight above that temperature. A two-step decomposition reaction was observed with both polymers XIII and XIV, the first decomposition being comparatively shorter.
Similar polymerization studies were carried out using compounds (VII) and (X) but the resulting polymers were more brittle in nature than those of compounds (V) and (IX). These results indicate that the desired ratio of ether and methylene amine used in preparing compound (IX) provides the preferred properties.
EXAMPLE 8
Test laminates were prepared by coating graphite cloth (8 harness satin weave cloth, designated as a style 133 fabric), with a DMF/acetone solution of compound (IX) and drying the resulting prepregs in an oven at 110-115 degrees C. for ten minutes. The prepregs were assembled in 4 or 9 plies and pressed between aluminum plates covered with a teflon film release sheet in a press maintained at 170 degrees C. for thirty minutes. The temperature was then kept at 225 degrees C. for two hours, and then at 250 degrees C. for thirty minutes. The pressure during curing was maintained at about 100 psi. The curing may also be carried out in an autoclave, using a vacuum bag.
Laminates from compound (V) were prepared in a similar way. The resin content of the laminates was determined by boiling with concentrated nitric acid.
Table IV below shows the data from physical tests done on the graphite composites made with resins of compounds (V) and (IX). Comparative results are also provided for graphite laminates made with bismaleimide of 4,4'-diaminodiphenylmethane and with the commonly used Ciba Geigy MY-720 epoxy system, cured with diaminodiphenyl sulfone (DDS). The results obtained show that the resin of compound (IX) is comparable to the epoxy system and superior to the bismaleimide system. The mechanical property value may be altered somewhat by varying the processing conditions.
TABLE IV______________________________________Physical Properties of Graphite Cloth Laminates Bisaspartimides Resin Resin Bismal-Property tested (V) (IX) Epoxy.sup.a eimide.sup.b______________________________________Resin content (%) 18 18 25 34.3Density (g/cm.sup.3) 1.31 1.31 1.57 1.554LOI (ASTM D2863; 54.2 56.2 45 58.4% O.sub.2)Flammability Non- Non- Non- Non- burning burning burning burningFlexural strength (psi) 56,102 68,020 79,808 40,014(ASTM D790; 386 470 550 276MN/m.sup.2)Flexural modulus (psi) 7.03 × 9.12 × 6.8 × 7.03 × 10.sup.6 10.sup.6 10.sup.6 10.sup.6(MN/m.sup.2) 48,461 62,883 46,880 48,461Tensile strength (psi) 52,406 69,525 51,639 21,286(ASTM D638; 362 480 356 147MN/m.sup.2)Elongation at 4.33 4.89 2.09break (%)Tensile modulus (psi) 3.0 × 4.5 × 4.4 × 2.5 × 10.sup.6 10.sup.6 10.sup.6 10.sup.6ASTM D738; 20,682 31,023 30,330 17,235MN/m.sup.2)Short beam shear (psi) 4,280 5,892 7,749 3,567(ASTM D2344; 29.5 40.62 53.42 24.59MN/m.sup.2)______________________________________ .sup.a Compared to the commonly used epoxy, CibaGeigy MY720 (tetraglycidylamine of 4,4diaminodiphenylmethane) cured with 4.4diaminodiphenylsulfone (DDS). .sup.b Bismaleimide of 4,4diaminodiphenylmethane.
EXAMPLE 9
The structure of the polymer obtained from compound (IX) was determined from its IR and NMR spectra. Based on observation of these spectra, the following structure was assigned for the resin polymer (XIII) of compound (IX). ##STR7## It should now be readily apparent to those skilled in the art that novel amine terminated bisaspartimides, a process for preparation of these compounds, new polymers of these compounds and laminates in accordance with the invention has been provided. It should further be apparent to those skilled in the art that various changes in form and details of the invention as described above may be made. It is intended that such changes be included within the spirit and scope of the claims appended hereto. | Novel amine terminated bisaspartimides, especially 4,4'-bis{N 2 -[4-(4-aminophenoxy)phenyl]aspartimido}diphenylmethane are prepared by a Michael-type reaction of an aromatic bismaleimide and an aromatic diamine in an aprotic solvent. These bisaspartimides are thermally polymerized to yield tough, resinous polymers cross-linked through --NH-- groups. Such polymers are useful in applications requiring materials with resistance to change at elevated temperatures, e.g., as lightweight laminates with graphite cloth, molding material prepregs, adhesives and insulating material. | 1 |
TECHNICAL FIELD OF THE INVENTION
[0001] The present invention relates to the design of energy photoconverters acting in a continuous and closed manner for producing biofuels and other products of interest by means of the mass culturing of phytoplankton.
[0002] The invention is comprised within the technical field of the exploitation of renewable energy by means of the action of phytoplankton organisms that normally belong to the following taxonomic families: Chlorophyceae, Bacillariophyceae, Dinophyceae, Cryptophyceae, Chrysophyceae, Haptophyceae, Prasinophyceae, aphidophyceae . . . generally the taxonomic families comprising species of the chromophyte division, all of them characterized by being flagellated or nonflagellated single-celled organisms and with a strictly planktonic (holoplanktonic) life phase, or at least one of its phases being planktonic (meroplanktonic).
[0003] Particularly by means of the use of energy converters, products such as biofuels, byproducts such as naphthas, kerosene, thermal energy, electric energy, . . . are obtained.
STATE OF THE ART
[0004] Up until now, biofuels have been obtained from higher plant cultures, usually from the group of phanerogams or flowering plants (sunflowers, palm, European palm, . . . ), and usually on the terrestrial surface (land plants).
[0005] The obligation for the economic zones to comply with the objectives imposed by the Kyoto protocol on the reduction of CO 2 /SO 2 emissions and the emission of other gases causing the so-called greenhouse effect is forcing countries to search for alternative and renewable fuels to prevent possible penal taxes.
[0006] Although the production of solar and wind energy is increasing in some regions, these technologies are very expensive and are not viable in all climatic areas. In these conditions, biofuels have an important role as substitutes of fossil fuels, especially in transport and heating applications.
[0007] The production costs of biofuels from plants, such as palm and rapeseed oil have always been a reason for concern. Taking into account the low oil production indexes per hectare, enormous amounts of resources would be needed to reach commercial production. Land and water are two limited resources and it is preferable to use them to produce food products, which are furthermore more profitable for farmers. Intensive fertilization is furthermore a form of land and water pollution of the first order. Extensive single crop farming is also one of the main enemies of biodiversity.
[0008] Phytoplankton represents a viable solution to the previously discussed drawback given that about 50% of the dry mass of single-celled organisms is generally biofuel. In addition, the annual production per hectare of biofuel from phytoplankton is 40 times higher than with the second most cost-effective product, palm oil. A drawback is that the production of phytoplankton oil requires covering vast stretches of land with rather shallow water, as well as introducing large amounts of CO 2 , an essential element for phytoplankton to produce oil. Natural production systems such as phytoplankton ponds, have a relatively low cost but the harvesting process is very laborious and, therefore expensive. On the other hand, phytoplankton culturing is carried out in open systems, making it vulnerable to contamination and to problems for cultures, which may lead to total production loss. In this same sense, an advantage of the photoconverter described in the present invention is that the system is kept closed and in conditions such that the culture is not contaminated by bacteria, fungi, . . . because in addition to being closed, the culture is enriched by means of nutrients incorporating fungicides and antibiotics.
[0009] Within the field of the design of photoconverters for producing biofuels through photosynthetic microorganisms, two types of photoconverters could be clearly differentiated: open photoconverters, in which a direct exchange of matter between the culture and the air surrounding it is allowed, and closed photoconverters, in which this exchange is eliminated by means of the placement of a transparent physical medium allowing the passage of electromagnetic radiation but not the exchange of matter. The open photoconverters have many problems derived from the little control of the culturing conditions and possible contaminations, so their application is limited due to these drawbacks. However, closed photoconverters efficiently reduce these problems by means of greater control of the culturing conditions and possible contaminations and can reach a production rate that is 400 times higher than the production rate of sunflower.
[0010] Until now no systems similar to the photoconverter object of the present invention have been described which incorporate the advantages of being a closed system with a large volume and large diameters, which works continuously, which allows obtaining large amounts of biofuels or byproducts such as naphthas, glycerin, silicon-derived compounds, such as ferrosilicates, which may further obtain thermal and electric energy that does not contaminate given that all the possible residues, such as carbon dioxide, are recirculated in the system to be used as a nutrient for the phytoplankton, or which recirculates the water used as part of the culture medium so it can be reused . . . . The present invention therefore describes a novel system (photoconverter) including all these features which allows enormous versatility and is very environmental friendly.
[0011] Patent application WO 03/094598 A1 entitled “Photobioreactor and process for biomass production and mitigation of pollutants in flue gases” describes a generic photobioreactor model mainly focused on decontaminating COx, SOx and NOx type gases. It is basically a system working in a discontinuous manner (distinguishing between day/night photoperiod) and is open, its liquid medium not being axenic. It does not control nitrogen and carbon dioxide concentrations for the purpose of increasing biofuel production. It is not designed to work with monospecific or monoclonal algae strains. Its design does not contemplate biofuel production as the main objective, rather it is focused on gas purification. On the other hand, as regards the photosynthetic organisms it refers to, it does not demand conditions disabling the system and it has no controlled recirculation because the transport is done by a turbulent flow of bubbles.
[0012] Compared to the present invention object of the patent, a completely novel system is set forth which is based, in contrast, on the following features:
It is completely closed. It is completely axenic. It works continuously. It works with monospecific and monoclonal strains. It does not accept any photosynthetic organism, but rather it at least requires that they are not organisms forming biofouling on the inner surface of the photoconverter. It requires that the phytoplankton species do not form colonies. It requires that the phytoplankton species do not generate exo-mucilage. It requires that the cultured species contains at least 5% of fatty acids. It enhances the use of nonflagellated and floating phytoplankton species. It does not accept any type of liquids as culture medium, it focuses on freshwater, brackish water and sea water. Its main objective is to obtain metabolic synthesis compounds with energetic properties or with pre-energetic properties essentially aimed at obtaining biofuels.
DESCRIPTION
[0024] The present invention relates to an energy photoconverter for obtaining biofuels and other, though not less important, byproducts. Said photoconverter uses a Tichelmann-type flow control system which allows providing equal pressure in any part thereof and thus continuously controls the extraction.
[0025] A first aspect of the present invention consists of a photoconverter consisting at least of the following elements:
at least 50 decanting, extraction and flow control towers ( 1 ) per hectare of surface used. at least 15 tubes for conducting photosynthesis ( 2 ) for each decanting, extraction and flow control tower ( 1 ). at least 20 mixture and buffer tanks ( 3 ) per hectare of surface used. at least 15 recirculation pumps ( 4 ) per hectare of surface used. at least 15 heat exchangers ( 5 ) to maintain the temperature of the photoconverter per hectare of surface used. at least 15 desuperheaters ( 6 ) to reduce the inlet temperature of carbon dioxide ( 6 a ), hereinafter CO 2 , per hectare of surface used. at least 50 electromagnetic flow control valves ( 8 ) per hectare of surface used. at least 50 electromagnetic extraction valves ( 9 ) per hectare of surface. at least 50 control sensors ( 10 ) of the culture medium per hectare of surface. at least 50 oxygen extraction valves ( 11 ) per hectare of surface. at least 50 hydrogen extraction valves ( 12 ) per hectare of surface. at least 5 decanting tanks ( 14 ) per hectare of surface. 100% natural light inlets ( 15 ) of the useful surface. at least 100 artificial lighting lamps ( 16 ) per hectare of surface. at least 5 control panels ( 17 ) per hectare of surface. at least 5 recirculation systems ( 18 ) per hectare of surface. at least 2 cooling towers or condensers ( 19 ) per hectare of surface. at least 50 densimeters ( 20 ) per hectare of surface. at least 5 pumps ( 21 ) for reintroducing the liquid from ( 14 ) per hectare of surface.
[0045] The decanting, extraction and flow control towers ( 1 ) contain at least densimeters ( 20 ), oxygen extraction valves ( 11 ) located in the upper part thereof and hydrogen extraction valves ( 12 ) and they have gas sensors ( 13 ) coupled thereto, which gas sensors act such that they open at a higher gas concentration. They are transparent tubes having a diameter from 0.80 to 1.50 meters with a height from 3 to 5 meters. In addition, they are equipped with electromagnetic extraction valves ( 9 ) in the lower part thereof and with nutrient ionization injectors ( 7 ) next to them, gas extraction valves in the upper part ( 11 ) and motor-driven Tichelmann-type flow circulation valves.
[0046] The tubes for conducting photosynthesis ( 2 ) can be horizontally or vertically arranged and are arranged perpendicular to the decanting, extraction and flow control towers ( 1 ). In addition, photosynthesis is carried out therein by means of the phytoplankton present therein and therefore these tubes are preferably made of a transparent material so as to allow the passage of electromagnetic radiation during hours of sunlight. In this same sense they contain fiber-optic ( FIG. 2 , 22 ) acting as an interior artificial light diffuser. Other external elements of the tubes for conducting photosynthesis ( 2 ) are electromagnets ( FIG. 2 , 24 ) which accelerate the molecular electron exchange. These tubes have a diameter comprised within the range from 100 to 200 millimeters, a length comprised within the range from 6 to 12 meters, a useful lighting surface comprised within the range from 0.30 m 2 /m and 0.70 m 2 /m and an internal volume comprised within the range from 7 l/m to 18 l/m. There is a separation of at least 250 millimeters between these tubes so as to allow light diffusion.
[0047] The mixture and buffer tanks ( 3 ) contain nutrients necessary for the development and growth of the phytoplankton mainly contained in ( 1 ) and ( 2 ). They are cylindrical shaped, made of a transparent material and have an internal volume comprised within the range from 500 to 3000 m 3 . With respect to the mixture and buffer tanks ( 3 ), they are made of a transparent material, are cylindrical and are arranged vertically. They have a level and nutrient inlet control using pH, temperature and concentration sensors, etc.
[0048] The culturing conditions of the phytoplankton in the photoconverters are as follows:
Temperature: from 15 to 35° C., preferably from 20 to 30° C. Sunlight intensity: 600 to 800 watts/m 2 . Artificial light intensity: 4 to 30 watts/m 2 . Photoperiod: 12-24 hours. Salinity: 0 per thousand up to 50 per thousand. Phytoplankton concentration in the culture medium: from 1,000,000 of cells/ml up to 400,000,000 cells/ml. pH: from 7 to 8.4.
[0056] When referring to nutrients, these nutrients are carbon dioxide, hereinafter CO 2 , NOx, vitamins, antibiotics, fungicides, water, trace elements and orthophosphoric acid.
[0057] The antibiotics added to the culture are a mixture of penicillin and streptomycin at a concentration range from 100 to 300 mg/l each, preferably at a concentration range from 150 to 250 mg/l and more preferably at a concentration of 200 mg/l for each of the components of the mixture.
[0058] The fungicides added to the culture are a mixture of griseofulvin and nystatin at a concentration range from 100 to 300 mg/l each, preferably at a concentration range from 150 to 250 mg/l and more preferably at a concentration of 200 mg/l for each of the components of the mixture.
[0059] The water added for the phytoplankton culture can be freshwater, brackish water or salt water.
[0060] The recirculation pumps ( 4 ) are centrifugal-type pumps and allow a flow rate comprised within the range from 4 to 100 cm/sec.
[0061] The heat exchangers ( 5 ) are laminar flow plate-type exchangers, are controlled by temperature sensors and are used to maintain the temperature by means of water from the cooling towers or condenser ( 19 ) of the system.
[0062] The desuperheaters ( 6 ) are laminar flow plate-type desuperheaters and have the purpose of reducing the inlet temperature of CO 2 and NO x ( 6 a ) coming from a pyrolysis gasifier.
[0063] Pyrolysis gasifier is understood to be a combustion process occurring at a temperature ranging between 800 and 1200° C. and which allows using and recycling most of the available waste. The process allows treating segregated or mixed urban and industrial waste. It is also technically possible, without any additional difficulties, to treat toxic waste, hospital waste, tires in the same industrial plants, i.e. to propose an overall definitive solution to the problems set forth by waste. The different advantages include the fact that the process is economically viable and less expensive than any other process, and particularly, incineration, thermolysis, methanation processes, and the fact that the process is completely ecological, without any environmental impact and offers a definitive solution to the waste problem, i.e., a “zero dump” solution. The pyrolysis gasifier achieves that all the waste is transformed into synthesis gas, hydrochloric acid, hydrofluoric acid and hydrogen sulfide, the latter three being three products which can be relatively easily made inert.
[0064] A synthesis gas is understood as a gas formed by a mixture of carbon monoxide, hereinafter CO, and hydrogen, hereinafter H 2 , which is obtained from a mixture of methane, hereinafter CH 4 , and oxygen, hereinafter O 2 , obtained from the air and steam by means of a pyrolysis gasifier.
[0065] The photoconverter can additionally include at least 50 ion sprayers ( 7 ) per hectare of surface, such that the nutrients are ionized and better and more efficient assimilation of the nutrients by the phytoplankton contained in ( 1 ) and ( 2 ) is thus allowed. Ion sprayer is understood as any system known in the state of the art that is able to ionize molecules.
[0066] The electromagnetic flow control or extraction valves ( 9 ) are located at the base of the decanting, extraction and flow control towers ( 1 ) and depend on photovalves operating by the difference of the light intensity between two points (controlled opening).
[0067] The control sensors ( 10 ) control the temperature, pH, the carbon dioxide, oxygen, trace element, antibiotic and fungicide concentration.
[0068] The photoconverter can additionally contain at least 5 gas sensors ( 13 ) per hectare of surface.
[0069] The decanting tanks ( 14 ) separate the biomass produced by the phytoplankton of the water of the culture medium. These decanting tanks are static tanks. The separated biomass contains, among other products and in no limiting sense, lipids, carbohydrates and products derived from the secondary metabolism of the phytoplankton. A transesterification reaction is carried out in the lipids present in the biomass separated by ( 14 ) such that biofuels and other energetic products are produced.
[0070] The carbohydrates obtained from the biomass separated by ( 14 ) are subjected to catalysis such that naphthas, kerosenes, polymers and gases coming from the catalysis of carbohydrates are obtained.
[0071] Transesterification refers to the chemical reaction by means of which the alkoxy group of an ester is exchanged for another alcohol, as shown in the following reaction:
[0000]
[0072] To carry out transesterification of the lipids obtained as part of the biomass produced by the phytoplankton described in this process, ethanol and methanol from a Fischer Tropsch-type reactor are used, which reactor is in turn fed by means of synthesis gas, steam and heat from a pyrolysis gasifier for biomass or waste from dumps. On the other hand, the biomass pyrolysis gasifier produces CO 2 and NO x which are part of the nutrients used for the feeding and growing cultured phytoplankton present in ( 1 ) and ( 2 ). The excess gases of the pyrolysis gasifier are furthermore reused to obtain electric and thermal energy, the latter being reused for desalinization.
[0073] A greenhouse-type system allows light to pass through to the natural light inlets ( 15 ), which are covered with translucent plastic, to limit the light or electromagnetic radiation intensity depending on the season of the year. In this same sense, the electromagnetic energy supplied comprises wavelengths of the spectrum ranging from 430 to 690 nm.
[0074] In addition, the decanting, extraction and flow control towers ( 1 ) and tubes for conducting photosynthesis ( 2 ) contain fiber-optic ( FIG. 2 , 22 ), which is controlled by photosensors ( FIG. 2 , 23 ) which in turn allow measuring the interior luminous intensity.
[0075] The control panels ( 17 ) control the injection of the different nutrients of the culture medium flow.
[0076] The recirculation systems ( 18 ) cause a Venturi-type effect which consists of the pressure of the fluid in the current of a fluid inside a closed conduit being reduced as the velocity increases when it passes through an area having a smaller section. If at this point of the conduit the end of another conduit is introduced, the fluid contained in this second conduit is suctioned for recirculation to prevent the algae from being destroyed due to the pressure.
[0077] The pumps ( 21 ) for reintroducing liquid are connected to the decanting tanks ( 14 ), such that the water separated in ( 14 ) recirculates to ( 3 ) passing through ( 21 ).
[0078] Another aspect of the present invention are the products obtained by means of the photoconverter, such that mainly biofuels are obtained, in addition to pharmacopeial products such as fatty acids and lutein, among others, cosmetic products such as glycerin, pigments and emulsifying substances, industrial products with a high silica content such as borosilicates and ferrosilicates, fertilizing products, agricultural products, industrial products and livestock products, and thermal and electric energy.
BRIEF DESCRIPTION OF THE DRAWINGS
[0079] FIG. 1 shows a representative diagram of the photoconverter object of the present invention with each of its parts and fittings for the use of solar and artificial electromagnetic energy for the purpose of obtaining, among other products, biofuels.
[0080] FIG. 2 shows a representative diagram of a section of the tubes for conducting photosynthesis ( 2 ), with all its external and internal components.
EMBODIMENT
[0081] An inoculum of a phytoplankton strain is introduced in ( 3 ), culture medium and nutrients are added which are detected and regulated by means of ( 10 ) and ( 17 ). Circulation thus begins so as to establish a continuous flow within which the phytoplankton cells will travel, at the same time reproducing through ( 1 ) where they are insufflated with carbon dioxide ( 6 a ) coming from ( 6 ) which controls the temperature and are ionized in ( 7 ), and then they will move to ( 2 ), uptaking the electromagnetic energy by means of ( 15 ) and ( 16 ) and ( 22 ), in order to conduct photosynthesis.
[0082] This is where the luminous intensity is controlled by means of ( 23 ) and in ( 24 ) is where the electromagnetic field aids in polarizing the CO 2 molecules, thus aiding in their dissolution and thus increasing the biomass, rich in lipids and carbohydrates, among other products. Then it will go to the next ( 1 ), also with CO 2 , with turbulence being generated and to stabilize itself, the phytoplankton tries to float in the medium. For each turbulence step, O 2 is lost by means of ( 11 ) and is detected by ( 13 ), and the same occurs for H 2 by means of ( 12 ) and is detected by ( 13 ). A recirculation process ( 8 ) is carried out within a Tichelmann-type pressure equilibrium process until the phytoplankton biomass is sufficient and detected by ( 20 ) in order to begin the extraction of part of it through ( 9 ) and from there the extracted part goes to ( 14 ), in which the water is separated from the biomass and is again propelled by ( 21 ) to the Venturi-type recirculation systems ( 18 ), finally going to ( 3 ) and to ( 1 ). The part that is not extracted due to a lack of density and therefore not detected by ( 20 ) is reintroduced into the system by ( 4 ), passing through ( 5 ) to maintain its temperature. | The present invention relates to the design of energy photoconverters which act in a continuous and closed manner for producing biofuels and other products of interest by means of the mass culturing of phytoplankton. | 2 |
CROSS-REFERENCES TO RELATED APPLICATIONS
This application claims the benefit of application Ser. No. 60/106,827 filed Nov. 3, 1998.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
Not applicable.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to the blending of polymeric materials and fillers to form free flowing particles.
2. Description of the Related Art
U.S. Pat. No. 5,552,457 is directed to a process for making resin-composite particulates of syndiotactic-1,2-polybutadiene and carbon black without using a conventional mixer. The carbon black and resin are mixed in an aqueous medium at an elevated temperature above the melting point or softening point of the resin, the medium is cooled and the masterbatch powder is recovered.
U.S. Pat. No. 3,920,604 is directed to a process for producing pourable, filler-containing polymer particles in which the polymer is dissolved in a volatile organic solvent, carbon black is added to the dissolved polymer, and the solvent is flash evaporated.
U.S. Pat. No. 4,994,534 is directed to the formation of sticky polymers in which the polymerization is said to take place at a temperature in excess of the softening temperature of the polymer, and in the presence of a particulate material having a mean particle size of from about 0.01 to about 10 micron meters.
BRIEF SUMMARY OF THE INVENTION
In one aspect, the present invention relates to a method for the formation of a free flowing polymer/filler masterbatch powder, which method comprises intimately mixing a polymer and a filler for a time and under shear conditions sufficient to convert the components into a free flowing associated composition of polymer and filler.
In another aspect, the present invention relates to the product of the method set forth above.
In yet another aspect, the present invention relates to a molded or extruded article made from the product set forth above.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a means for forming a free flowing blend of a polymeric material and a filler. Suitable polymeric materials include both natural rubber and synthetic rubbers. Synthetic rubbers include, but are not limited to, for example, ethylene/alpha-olefin/non-conjugated polyene (EPDM) rubbers, ethylene/alpha-olefin (EPR) rubbers, styrene/butadiene rubbers, acrylonitrile/butadiene (NBR) rubbers, polychloroprene rubbers, polybutadiene rubbers, isobutylene-isoprene copolymers, etc. The polymeric component also includes mixtures of two or more different polymeric materials. In a preferred embodiment, the polymeric material, prior to blending, is substantially or completely free of filler material.
Suitable fillers include any filler conventionally used in polymer compounding, including carbon black, hydrated amorphous silica, diatomaceous earth, talc, calcium carbonate, etc., and may include mixtures of two or more different fillers.
The powders according to the present invention may have a weight ratio of polymer to filler from about 1:0.15 to about 1:10, preferably from about 1:0.15 to about 1:1.5, depending on the constituent materials and the application therefor.
The polymer/filler powders of the present invention may be processed by well known means into, e.g., various types of end product molded or extruded articles, including tires, hoses, roof sheeting, weatherstripping, belts, wire and cable covers, etc., and may contain other conventional additives such as processing aids, antioxidants, antiozonants, etc.
The powders of the present invention may be formed by subjecting the desired amounts of polymer and filler, preferably in a substantially dry state, to shear conditions in an internal mixer such as Brabenders, continuous screw extruders, Banburys, etc. and for a time sufficient to form the powder. For present purposes, a dry state is defined as free from polymerization medium solvents and/or water. In a preferred embodiment, the polymer and filler are blended in a mixer, preferably for about 1 to about 5 minutes. As will be demonstrated more fully below, the quality of the powder may be controlled by varying a number of parameters, including the volume loading of the mixer, mixing temperature, mixing time, mixing shear stress, and the blend ratio of the polymer and filler. In certain embodiments, the filler and/or polymer may additionally comprise an extender oil.
The following non-limiting examples are illustrative of the processes and products of the present invention.
TABLE 1. EXAMPLES 1-4
TABLE 1
Example
1
2
3
4
ROYALENE ® 3275:N-650
1:1.5
1:1.5
1:1.5
1:1.5
Volume Loading, %
71
66
62
57
Torque, m-gm
270
95
35
22
Sieve Size
Wt % of Particles Retained
#8
39
0
0
0
#20
32
25
6
7
#30
29
75
94
93
Non-Sintering Rating
2
2
1-2
1
In these examples, it is demonstrated that a free flowing particle that will not agglomerate under normal conditions may be formed from a blend of a polymer and carbon black. The polymer used was ROYALENE® 3275 (Uniroyal Chemical Co., Middlebury, Conn.) which is an EPDM having a Mooney viscosity (ML 1+4 @ 125° C.) of 60, an ethylene/propylene ratio of 57/43 and an ethylidene norbornene content of 2%. The carbon black was N-650 from Cabot Corp. The designated amounts of EPDM and N-650 were charged to a Brabender mixer with a mixing capacity of 65 cc. The carbon black was added first, followed by solid pieces of the EPDM polymer. The mixing unit is heated to 65° C., and the blend is mixed at 50 rpm for 5 minutes under a ram pressure of 40 psi. The temperature and the torque (m-gm) are recorded at the end of the 5 minute mix. The lower the final temperature and torque, the higher the amount of small particles which produce an excellent non-sintering rating.
The weight ratio of polymer to carbon black in Examples 1-4 is held constant at 1:1.5, and the volume loading was varied between 57 and 71 percent. Volume was calculated based on the EPDM density (0.86 g/cc) and the carbon black density (1.8 g/cc).
After mixing, the ingredients are removed from the mixer and the particle size distribution is determined by sieving through a series of U.S.A. Standard Sieves series (ASTM designation E11) of the following sizes:
#4 (0.187 inch), #5 (0.157 inch), #8 (0.094 inch), #20 (0.033 inch) and #30 (0.023 inch). The percentage of particles retained on each sieve size is calculated by weight. The results are presented in Table 1.
In examples 1-4 the particle size distribution shows that as the volume loading and mixing torque decreases, the amount of smaller size particles increases. At the start of the mix the temperature and torque value increases, but after several minutes both will decrease as the particles are formed. Examples 3 and 4 give the maximum percentage of small particles between a volume loading of 57% to 62%. Examples 1 and 2 at 66% and 71% volume loading give lower amounts of small particles. These examples clearly show that a specific volume loading is required to give the smallest rubber/carbon black particle.
The product produced in Example 4, which is comprised primarily of #30 size particles, was evaluated in a non-sintering test and was found to give an excellent rating of 1. Polypropylene and polyethylene commercial resins in pellet form were used as control samples, and they both had a rating of 2 under the same test conditions.
The sintering test is performed as follows. A piece of 2 inch×2 inch I.D. square tubing 4 inches long is capped off on one end to contain the sample. A weighted ram is a piece of 1-⅞ inch×1-⅞ inch O.D. square tubing capped off on one end and of sufficient length to contain the necessary weights, in this instance 1037 grams. Fifty grams of material to be tested is poured into the base of the first tube. The weighted ram is placed on the material, and the entire unit is placed in an oven for 5 days at 120° F. After the 5 days, the ram is removed, and the sample is evaluated according to the following ratings: 1=excellent (loose and free flowing); 2=good (slightly packed, flows out with slight probe); 3=fair (packed, but breaks up easily); 4=poor (packed, but breaks up with effort); and 5=bad (packed, will not break up except with extreme effort).
Table 2. Examples 5-7
TABLE 2
Example
5
6
7
ROYALENE ® 3275:N-650
1:1
1:1
1:1
Volume Loading, %
56
50
40
Torque, m-gm
300
25
11
Sieve Size
Wt % of Particles Retained
#8
6
1
#20
33
19
#30
61
80
Non-Sintering Rating
(a)
2
1
(a) Ingredients massed together; no particles formed.
In this series, the ratio of ROYALENE® 3275 EPDM and N-650 carbon black was held constant at 1:1 and the volume loading was varied between 40% and 56%. These were mixed under the same conditions used in examples 1-4. The results in Table 2 show that example 5, at a volume loading of 56%, had a high torque value of 300 m-gm and the blend massed together. Example 7, at the loading of 40%, produced the highest percentage of smaller particles (19% of #20 and 80% of #30) and it had a non-sintering rating of 1.
Table 3. Examples 8-10
TABLE 3
Example
8
9
10
ROYALENE ® 3275:N-650
1:0.5
1:0.5
1:0.5
Volume Loading, %
50
44
35
Torque, m-gm
170
40
12
Sieve Size
Wt % of Particles Retained
#8
68
10
#20
30
35
#30
2
55
Non-Sintering Rating
(a)
3
1, 2
(a) Ingredients massed together; no particles formed.
In this series, the ratio of ROYALENE® 3275 EPDM and N-650 carbon black was held constant at 1:0.5 and the volume loading varied between 35% and 50%. These were mixed under the same conditions used in examples 1-4. The results in Table 3 show that example 8, at a loading of 50%, massed together. Examples 9 and 10, at volume loading between 35% and 44%, yield the largest percentage of smaller particles. Example 10 was tested twice and had non-sintering ratings of 1 and 2.
Table 4. Examples 11-12
TABLE 4
Example
11
12
ROYALENE ® 3275:N-650
1:0.25
1:0.25
Volume Loading, %
39
32
Torque, m-gm
24
11
Wt % of
Sieve Size
Particles Retained
#8
45
10
#20
51
49
#30
4
41
Non-Sintering Rating
—
3
In this series, the ratio of ROYALENE® 3275 EPDM and N-650 carbon black was held constant at 1:0.25 and the volume loading varied between 32% and 39%. These were mixed under the same conditions used in examples 1-4. The results in Table 4 show that example 12, at 32% loading, has the largest percentage of smaller particles.
The data in examples 1-12 clearly show that the relationship between the blend ratio and volume loading to produce a small particle blend of EPDM and N-650 carbon black. As the EPDM:N-650 blend ratio decreases, a lower volume loading is required to produce the largest amount of the small particles.
Table 5. Examples 13-14
TABLE 5
Example
13
14
ROYALENE ® 3275:N-650
1:0.5
1:0.5
Volume Loading, %
49
34
Mixing Power, KW
0.5
0.1
Wt % of
Sieve Size
Particles Retained
#4
4
#5
4
#8
13
#20
34
#30
45
Non-Sintering Rating
(a)
1-2
(a) Ingredients massed together; no particles formed.
In this series, the blend ratio of ROYALENE® 3275 EPDM and N-650 carbon black was held constant at 1:0.5 and the volume loading varied between 34% and 49%. Mixing was done in a Farrel Banbury mixer, Model BR 1600 with a capacity of 1570 cc for comparison with data generated in examples 8-10 which were mixed in a 65 cc Brabender unit. The carbon black and polymer were added to the Banbury mixer which was preheated to 65° C. The ram was closed and the blend was mixed at a rotor speed of 100 rpm for 5 minutes. The kilowatts of power were recorded at the end of the mix. The resulting particles were removed, cooled to room temperature, and sieved. The data on these mixes are tabulated in Table 5. Example 13, at the loading of 49%, did not form a particulate product but massed together. Example 19 did form particles at the lower volume loading. Example 14 at a 34% volume loading had the maximum amount of smaller particle sizes. The results in example 10 using the smaller Brabender mixer indicated that the optimum loading was 35%. Since the volume loadings are similar in both the 65 cc and a 1570 cc mixer, it indicates that this process can be scaled up in larger mixing equipment with similar results.
To further illustrate the invention, the product from example 14 was sieved into particle sizes. Non-sintering results show that the larger particle sizes have poor ratings, whereas the smaller particles have good ratings as shown below:
Sieve Size
#4
#5
#8
#20
#30
Rating
5
5
3
2
2
Table 6. Examples 15-16
TABLE 6
Example
15
16
BJLT-M50:N-650
1:1.5
1:1.5
Volume Loading, %
65
50
Torque, m-gm
350
5
Wt % of
Sieve Size
Particles Retained
#4
1
0
#5
3
0
#8
7
0
#20
27
3
#30
62
97
Non-Sintering Rating
—
3
This series utilizes PARACRIL® BJLT-M50 (Uniroyal Chemical Company, Inc., Middlebury, Conn.), a nitrile polymer with a Mooney viscosity (ML 1+4 @ 125° C.) of 50, an acrylonitrile content of 32.6% and a density of 0.99 g/cc. The same mixing procedure of examples 1-4 is used. The blend ratio of BJLT-M50 and N-650 carbon black was held constant at 1:1.5 and the volume loading varied between 50% and 65%. The data in Table 6 show that the volume loading at 50% gives the largest percentage of smaller particle sizes. Example 16 had a non-sintering rating of 3 (fair).
Table 7. Examples 17-20
TABLE 7
Example
17
18
19
20
BJLT-M50:N-650
1:1
1:1
1:05
1:0.25
Volume Loading, %
50
40
30
25
Torque, m-gm
480
4
160
100
Sieve Size
Wt % of Particles Retained
#4
0
#5
0
#8
0
#20
21
#30
79
Non-Sintering Rating
(a)
3
(a)
(a)
(a) Ingredients massed together; no particles formed.
In examples 17 and 18, the blend ratio of BJLT and N-650 carbon black is held constant at 1:1 and the volume loading is varied between 40% and 50%. The same mixing procedure in examples 1-4 was used. The data in Table 7 show that Example 17 at the 50% volume loading did not produce any particulates and the ingredients massed together. Example 18 at the lower loading of 40% did produce a large percentage of small particles. Example 18 had a non-sintering rating of 3 (fair).
In examples 19-20, the blend ratios of BJLT-M50 and N-650 are held at 1:05 and 1:0.25. The same mixing procedure in examples 1-4 is used. The data in Table-7 show that both example 19 at a ratio of 1:0.5 and a volume loading of 30% and example 20 at a blend ratio of 1:0.25 at a volume loading of 25% massed together and did not form a particulate material.
The data in examples 15-20 show that the present invention can be used with an NBR polymer to produce a free flowing particulate material at an NBR:N-650 blend ratio higher than 1:0.5.
Table 8. Examples 21-22
TABLE 8
Example
21
22
SBR-1502:N-650
1:1.5
1:1.5
Volume Loading, %
70
55
Torque, m-gm
80
10
Wt % of
Sieve Size
Particles Retained
#4
0
0
#5
0
0
#8
0
0
#20
32
5
#30
68
95
Non-Sintering Rating
—
2
This series utilizes SBR-1502 (Copolymer Corp.), a styrene-butadiene polymer with a Mooney viscosity (ML 1+4 @ 100° C.) of 52, a bound styrene content of 23.5%, and a density of 0.93 g/cc. The same mixing procedure in examples 1-4 was used. The SBR-1502:N-650 carbon black blend ratio was held constant at 1:1.5 and the volume loading varied between 55% and 70%. The data in Table 8 show that the smaller particle sizes are maximized between 55% and 70% volume loading. Example 22 had a non-sintering rating of 2 (good).
Table 9. Examples 23-24
TABLE 9
Example
23
24
SBR-1502:N-650
1:1
1:1
Volume Loading, %
55
45
Torque, m-gm
120
2
Wt % of
Sieve Size
Particles Retained
#4
24
0
#5
6
0
#8
18
0
#20
28
17
#30
24
83
Non-Sintering Rating
—
2
In this series, the SBR-1502:N-650 blend ratio is held constant at 1:1 and the volume loading varied between 45% and 55%. The same mixing procedure in examples 1-4 was used. The data in Table 9 show that the smaller particles are maximized around a volume loading of 45%. Example 24 had a non-sintering rating of 2 (good).
Table 10. Examples 25-26
TABLE 10
Example
25
26
SBR-1502:N-650
1:0.5
1:0.5
Volume Loading, %
45
40
Torque, m-gm
190
nil
Wt % of
Sieve Size
Particles Retained
#4
0
#5
0
#8
10
#20
43
#30
47
Non-Sintering Rating
(a)
3
(a) Ingredients massed together; no particles formed.
In this series, the SBR-1502:N-650 blend ratio is held constant at 1:0.5 and the volume loading varied between 40% and 45%. The same mixing procedure in examples 1-4 was used. The data in Table 10 show that example 25 at a 45% volume loading masses together. Example 26 at a volume loading of 40% produces the highest percentage of smaller particles. Example 26 had a non-sintering rating of 3 (fair).
Table 11. Examples 27-28
TABLE 11
Example
27
28
SBR-1502:N-650
1:0.25
1:0.25
Volume Loading, %
45
40
Torque, m-gm
140
2
Sieve Size
Wt % of Particles Retained
#4
(a)
8
#5
(a)
12
#8
(a)
31
#20
(a)
30
#30
(a)
19
(a) Ingredients massed together; no particles formed.
In this series, the SBR-1502:N-650 blend ratio is held constant at 1:0.25 and the volume loading varied between 40% and 45%. The same mixing procedure in examples 1-4 was used. The data in Table 11 show that example 27 at a volume loading of 45% masses together. A volume loading of 40% gives the highest percentage of smaller particles (example 28).
Table 12. Examples 29-32
TABLE 12
Example
29
30
31
32
Butyl 065:N-650
1:1.5
1:1.5
1:1
1:1
Volume Loading, %
50
45
40
35
Torque, m-gm
160
1
180
5
Sieve Size
Wt % of Particles Retained
#4
0
0
#5
0
1
#8
2
14
#20
29
35
#30
69
50
Non-Sintering Rating
(a)
2
(a)
3
(a) Ingredients massed together; no particles formed.
Examples 29-30 utilize Butyl 065 (Exxon), an isobutylene-isoprene copolymer, with a Mooney viscosity (ML 1+8 @ 100° C.) of 45, an unsaturation of 0.8 mole percent, and a density of 0.92 g/cc. The same mixing procedure in examples 1-4 is used. The Butyl 065:N-650 blend ratio is evaluated at 1:1.5. The volume loading is varied between 45% and 50%. The data in Table 12 show that the highest percentage of particulate material is produced at a volume loading of 45%. Example 30 had a non-sintering rating of 2 (good).
Examples 31-32 utilize Butyl 065 and carbon black at a blend ratio of 1:1. The volume loading is varied between 35% and 40%. The data in Table 12 show that the highest percentage of particulate material is produced at a volume loading of 35%. Example 32 had a non-sintering rating of 3 (fair).
Table 13. Examples 33-36
TABLE 13
Example
33
34
35
36
Butyl 065:N-650
1:0.5
1:0.5
1:0.25
1:0.25
Volume Loading, %
45
40
50
45
Torque, m-gm
140
3
110
0
Sieve Size
Wt % of Particles Retained
#4
8
4
#5
7
3
#8
21
16
#20
28
37
#30
36
40
Non-Sintering Rating
(a)
3
(a)
4
(a) Ingredients massed together; no particles formed.
Examples 33-34 utilize Butyl 065 and carbon black at a blend ratio of 1:0.5. The volume loading is varied between 40% and 45%. The data in Table 13 show that the higher percentage of particulate material is produced at a loading of 40%. Example 34 had a non-sintering rating of 3 (fair).
Examples 35-36 utilize Butyl 065 and carbon black at a blend ratio of 1:0.25. The volume loading was varied between 45% and 50%. The data in Table 13 show that the higher percentage of particulate material is produced at a loading of 45%. Example 36 had a non-sintering rating of 4 (poor).
Table 14. Examples 37-38
TABLE 14
Example
37
38
Cisdene 1203:N-650
1:0.5
1:0.5
Volume Loading, %
60
50
Torque, m-gm
185
0
Wt % of
Sieve Size
Particles Retained
#4
0
#5
0
#8
5
#20
30
#30
65
Non-Sintering Rating
(a)
4
(a) Ingredients massed together; no particles formed.
This series utilizes Cisdene 1203 (American Synthetic Rubber), a cis-polybutadiene polymer with a Mooney viscosity (ML 1+4 @ 100° C.) of 45 and a specific gravity of 0.91 g/cc. The blends were mixed in the same procedure as in examples 1-4. The Cisdene 1203:N-650 carbon black ratio was held constant at 1:0.5 and the volume loading varied between 50% and 60%. The data in Table 14 show that example 37 at the higher volume loading of 60% massed together within the mixer. Example 38 at a loading of 50% gave the best distribution of particles.
Table 15. Examples 39-42
TABLE 15
Example
39
40
41
42
ROYALENE ® 3275:Austin Black
1:1.5
1:1.5
1:0.5
1:0.5
Volume Loading, %
50
35
40
25
Torque, m-gm
110
nil
22
nil
Sieve Size
Wt % of Particles Retained
#4
0
3
#5
2
5
#8
11
32
#20
31
37
#30
56
23
Non-Sintering Rating
(a)
2
(a)
3
(a) Ingredients massed together; no particles formed.
In examples 39 and 40, the ratio of ROYALENE® 3275 and Austin Black (ground coal) was held constant at 1:1.5 and the volume loading varied between 35% and 50%. These were mixed under the same conditions used in examples 1-4. The results in Table 15 show that example 39, at a volume loading of 50%, had a high torque value of 110 m-gm and the blend massed together. Example 40 at a volume loading of 35% had a non-sintering rating of 2.
In examples 41 and 42, the ratio of ROYALENE® 3275 and Austin Black (ground coal) was held constant at 1:0.5 and the volume loading varied between 25% and 40%. These were mixed under the same conditions used in examples 1-4. The results in Table 15 show that example 41, at a volume loading of 40%, massed together. Example 42 at a volume loading of 25% gave the largest percentage of smaller particles and it had a non-sintering rating of 3.
Table 16. Examples 43-46
TABLE 16
Example
43
44
45
46
ROYALENE ® 3275:Mistron Vapor
1:1
1:1
1:0.5
1:0.5
Volume Loading, %
30
25
30
25
Torque, m-gm
55
0
30
0
Sieve Size
Wt % of Particles Retained
#4
3
7
#5
7
8
#8
22
30
#20
30
33
#30
41
22
Non-Sintering Rating
(a)
2
(a)
2
(a) Ingredients massed together; no particles formed.
In examples 43 and 44, the blend ratio of ROYALENE® 3275 and Mistron Vapor (magnesium silicate) was held constant at 1:1 and the volume loading varied between 25% and 30%. These were mixed under the same conditions used in examples 1-4. The results in Table 16 show that example 43, at a volume loading of 30%, massed together. Example 44 at a volume loading of 25% gave a non-sintering rating of 2.
In examples 45 and 46, the blend ratio of ROYALENE® 3275 and Mistron Vapor (magnesium silicate) was held constant at 1:0.5 and the volume loading varied between 25% and 30%. These were mixed under the same conditions used in examples 1-4. The results in Table 16 show that example 45, at a 30% volume loading, masses together. Example 46 at a volume loading of 25% gave a non-sintering rating of 2.
Table 17. Examples 47-50
TABLE 17
Example
47
48
49
50
ROYALENE ® 3275:Paragon Clay
1:1.5
1:1.5
1:0.5
1:0.5
Volume Loading, %
35
30
35
25
Torque, m-gm
55
Nil
80
Nil
Sieve Size
Wt % of Particles Retained
#4
0
0
#5
0
2
#8
4
6
#20
28
36
#30
68
56
Non-Sintering Rating
(a)
2
(a)
3
(a) Ingredients massed together; no particles formed.
In examples 47 and 48, the blend ratio of ROYALENE® 3275 and Paragon Clay (hydrated aluminum silicate) was held constant at 1:1.5 and the volume loading varied between 30% and 35%. These were mixed under the same conditions used in examples 1-4. The results in Table 17 show that example 47, at a volume loading of 35%, massed together. Example 48 at a volume loading of 30% gave a non-sintering rating of 2.
In examples 49 and 50, the blend ratio of ROYALENE® 3275 and Paragon Clay (hydrated aluminum silicate) was held constant at 1:0.5 and the volume loading varied between 25% and 35%. These were mixed under the same conditions used in examples 1-4. The results in Table 17 show that example 49, at a volume loading of 35%, masses together. Example 50 at a volume loading of 25% gave a free flowing particulate with a non-sintering rating of 3.
Table 18. Examples 51-54
TABLE 18
Example
51
52
53
54
ROYALENE ® 3275:Atomite
1:1.5
1:1.5
1:0.5
1:0.5
Volume Loading, %
40
25
35
30
Torque, m-gm
100
nil
65
Nil
Sieve Size
Wt % of Particles Retained
#4
4
1
#5
5
1
#8
24
14
#20
23
55
#30
44
29
Non-Sintering Rating
(a)
2
(a)
3
(a) Ingredients massed together; no particles formed.
In examples 51 and 52, the blend ratio of ROYALENE® 3275 and Atomite (calcium carbonate) was held constant at 1:1.5 and the volume loading varied between 25% and 40%. These were mixed under the same conditions used in examples 1-4. The results in Table 18 show that example 51, at a volume loading of 40%, masses together. Example 52 at a volume loading of 25% gave a free flowing particulate with a non-sintering rating of 2.
In examples 53 and 54, the blend ratio of ROYALENE® 3275 and Atomite (calcium carbonate) was held constant at 1:0.5 and the volume loading varied between 30% and 35%. These were mixed under the same conditions used in examples 1-4. The results in Table 18 show that example 53, at a volume loading of 35%, masses together. Example 54 at a volume loading of 30% gave a free flowing particulate with a non-sintering rating of 3.
Table 19. Examples 55-58
TABLE 19
Example
55
56
57
58
ROYALENE ® 3275:HiSil 243
1:1.5
1:1.5
1:0.5
1:0.25
Volume Loading, %
60
55
25
25
Torque, m-gm
700
nil
nil
Nil
Sieve Size
Wt % of Particles Retained
#4
0
0
1
#5
0
1
2
#8
0
8
16
#20
9
36
44
#30
91
55
37
Non-Sintering Rating
(a)
1
2
2
(a) Ingredients massed together; no particles formed.
In examples 55 and 56, the blend ratio of ROYALENE® 3275 and HiSil 243 (precipitated, hydrated amorphous silica) was held constant at 1:1.5 and the volume loading varied between 55% and 60%. These were mixed under the same conditions used in examples 1-4. The results in Table 19 show that example 55 at a volume loading of 60% masses together. Example 56 at a volume loading of 55% gave a free flowing particulate with a non-sintering rating of 1.
In examples 57 and 58, the volume loading of ROYALENE® 3275 and HiSil 243 (precipitated, hydrated amorphous silica) was held constant at 25% and the blend ratio varied between 1:0.5 and 1:0.25. These were mixed under the same conditions used in examples 1-4. The results in Table 19 show that example 57 at a blend ratio of 1:0.5 gave a free flowing particle with a non-sintering rating of 2. Example 58 at a blend ratio of 1:0.25 gave a free flowing particulate with a non-sintering rating of 2.
Table 20. Examples 59-61
TABLE 20
Example
59
60
61
ROYALENE ® 3275:N-650
1:0.1
1:0.15
1:0.2
Volume Loading, %
30
30
30
Torque, m-gm
nil
nil
nil
Sieve Size
Wt % of Particles Retained
#4
1
1
1
#5
2
3
2
#8
26
21
17
#20
54
49
51
#30
17
26
29
Non-Sintering Rating
5
4
3
In this series, the volume loading of ROYALENE® 3275 and N-650 is held constant at 30% and the blend ratio is varied between 1:0.1 and 1:0.2. The same mixing procedure of examples 1-4 is used. The results in Table 20 show that example 59 at a blend ratio of 1:0.1 gives a particulate material, but it has a non-sintering rating of 5. Example 60 was prepared at a blend ratio of 1:0.15, and its particles have a non-sintering ratio of 4. Example 61 was prepared at a blend ratio of 1:0.2, and its particles have a non-sintering rating of 3.
TABLE 21
Non-Sintering
Example
ROYALENE ® :N-650
Rating
59
1:0.10
5
60
1:0.15
4
61
1:0.20
3
12
1:0.25
3
10
1:0.50
1, 2
The data in Table 21 clearly show that the lowest blend ratio limit of this invention that shows an improvement in the non-sintering rating is 1:0.15.
Table 22. Examples 62-64
TABLE 22
Example
62
63
64
ROYALENE ® 3275:N-650
1:0.5
1:0.5
1:0.5
Volume Loading, %
35
35
35
Mixing Temperature, ° C.
40
65
85
Torque, m-gm
35
12
0
Sieve Size
Wt % of Particles Retained
#4
51
0
0
#5
10
0
0
#8
24
10
9
#20
14
35
38
#30
1
55
53
Non-Sintering Rating
—
1, 2
2
In this series, the blend ratio of ROYALENE® 3275 and N-650 is held constant at 1:0.5, the volume loading is held constant at 35%, and the mixing temperature is varied at 40° C. and 85° C. The same mixing procedure in examples 1-4 is used. The data in Table 22 show that example 62 at 40° C. did produce a particulate material, but has the highest amount of larger size particles. Example 63 mixed at a temperature of 65° C. had a high level of smaller particle sizes with a non-sintering rating of 1-2. Example 64 was mixed at 85° C., and had a high level of smaller size particles and had a non-sintering rating of 2.
Table 23. Examples 65-69
TABLE 23
Example
65
66
67
68
69
ROYALENE ® 3275:N-650
1:1
1:1
1:1
40
1:1
Volume Loading, %
40
40
40
40
40
Mixing Time, minutes
0.75
1
2
3
4
Torque, m-gm
200
200
30
nil
nil
Sieve Size
Wt % of Particles Retained
#4
74
63
2
0
0
#5
4
5
2
0
0
#8
8
12
7
2
1
#20
9
14
32
20
19
#30
5
6
57
78
80
In this series, the blend ratio of ROYALENE® 3275 and N-650 is held constant at 1:1, the volume loading is held constant at 40%, and the mixing time is varied at 0.75, 1, 2, 3, and 4 minutes. The same mixing procedure in examples 1-4 was used. The data in Table 23 show that longer mixing times give a larger amount of smaller particle sizes. Example 67 takes 2 minutes to achieve a distribution of 32% of #20 size particles and 57% of #30 size particles.
Table 24. Examples 70-74
TABLE 24
Example
70
71
72
73
74
ROYALENE ® 3275:N-650
1:0.5
1:0.5
1:0.5
1:0.5
1:0.5
Volume Loading, %
35
35
35
35
35
Mixing Time, minutes
0.75
1
2
3
4
Torque, m-gm
100
100
12
Nil
nil
Sieve Size
Wt % of Particles Retained
#4
71
74
10
0
0
#5
3
3
3
1
1
#8
9
8
15
8
5
#20
11
11
38
38
34
#30
6
4
34
53
60
In this series, the blend ratio of ROYALENE® 3275 and N-650 is held constant at 1:0.5, the volume loading is held constant at 35%, and the mixing time is varied at 0.75, 1, 2, 3, and 4 minutes. The same mixing procedure in examples 1-4 was used. The data in Table 25 show that longer mixing times give a larger amount of smaller particle sizes. Example 73 takes 3 minutes to achieve a distribution of 38% of #20 size particles and 53% of #30 size particles.
The data in examples 70-74 show that longer mixing times are beneficial for producing a smaller size particulate. Blend ratios that are lower in carbon black content require more mixing time to produce a specific particle size distribution.
Table 25. Examples 75-76
TABLE 25
Example
75
76
ROYALENE ® 3275:Statex MRG-P
1:1.5
1:1.5
Volume Loading, %
35
30
Torque, m-gm
90
0
Wt % of
Sieve Size
Particles Retained
#4
(a)
0
#5
(a)
0
#8
(a)
10
#20
(a)
32
#30
(a)
52
(a) Ingredients massed together; no particles formed.
In this series, the blend ratio of ROYALENE® 3275 and Statex MRG-P is held constant at 1:1.5, and the mixer volume loading is varied between 30% and 35%. Statex MRG-P is composed of 100 phr N-650 carbon black and 50 phr of Sunpar 2280 oil. The same mixing procedure in examples 1-4 is used. The data in Table 25 show that example 75 at a volume loading of 35% did not form a free flowing particulate.
Example 76 at a volume loading of 30% did form a free flowing particulate composed of 32% of #20 size particles and 58% of #30 size particles.
These data show that oil is to a degree detrimental in this process but under the proper mixing conditions, a free flowing material could be possible.
Table 26. Examples 77-80
TABLE 26
Example
77
78
79
80
ROYALENE ® X4070:Filler Package A
1:1.5
1:1.5
—
—
ROYALENE ® X4234:Filler Package B
—
—
1:1.4
1:1.4
Volume Loading, %
60
50
55
50
Torque, m-gm
360
nil
320
Nil
Sieve Size
Wt % of Particles Retained
#4
0
0
#5
0
0
#8
0
0
#20
15
27
#30
85
73
Non-Sintering Rating
(a)
2
(a)
—
(a) Ingredients massed together; no particles formed.
In this series, ROYALENE® X70, an experimental EPDM having a Mooney viscosity of 62, an ethylene/propylene ratio of 70/30, and ENB of 2%, is mixed with a filler package that might be used in actual applications. Filler Package A is composed of 150 phr of the following ingredients (N-650, N-330, Austin Black, and Paragon Clay). Examples 77 and 78 are blends of ROYALENE® X70 and Filler Package A at a ratio of 1:1.5 mixed at a volume loading between 50% and 60%. Example 77 at a volume loading of 60% masses together. Example 78 at a volume loading of 50% gives a free flowing particle with a non-sintering rating of 2. Examples 79 and 80 are blends of ROYALENE® X34, an experimental EPDM having a Mooney viscosity (ML 1+4 @ 100° C.) of 65, an ethylene/propylene weight ratio of 60/40, and ENB % of 8.5, and Filler Package B at a ratio of 1:1.4 mixed at a volume loading between 50% and 55%. Filler Package B is composed of 140 phr of the following ingredients (N-660, N-550, and Whiting). Example 79 at a volume loading of 55% masses together. Example 80 at a volume loading of 50% gives a free flowing particulate with 73% of #30 size particles.
Table 27. Examples 81-83
TABLE 27
Example
81
82
83
SMR-CV60:N-650
1:1.5
1:1.5
1:1.5
Volume Loading, %
66
62
57
Torque, m-gm
114
74
79
Sieve Size
Wt % of Particles Retained
#4
0
0
0
#5
0
0
0
#8
1
1
1
#20
35
31
35
#30
64
68
64
Non-Sintering Rating
2
2
2
In this series, Natural Rubber, SMR-CV-60 with Mooney viscosity 60 was used. The ratio of SMR-CV-60 to Carbon Black N650 was kept constant 1:1.5, and the volume loading varied between 66% and 57%. The mixing procedure was the same as in examples 1-4. In all three cases, samples with non-sintering test rating of 2 were obtained.
Table 28. Example 84
TABLE 28
Example
84
TRILENE ® 77:N-650
1:1.5
Volume Loading, %
53
Torque, m-gm
11
Sieve Size
Wt % of Particles Retained
#4
0
#5
0
#8
1
#20
13
#30
86
Non-Sintering Rating
1
In this example, TRILENE® 77 was used which is an EPDM produced by Uniroyal Chemical. The nominal composition of TRILENE® 77 is: E/P weight ratio 75/25, % ENB 9.5, and its GPC weight average molecular weight is 40,000. The ratio of TRILENE® to Carbon Black N650 was 1:1.5 and the volume loading was 53%. The non-sintering test shows an excellent rating of 1. The mixing conditions were the standard, except that the temperature of the Brabender was 23° C. instead of 65° C.
Table 29. Examples 85-88
TABLE 29
Example
85
86
87
88
Solflex 1216:N-650
1:1.5
1:2.33
1:4
1:9
Volume Loading, %
57
57
45
33
Torque, m-gm
20
120
130
83
Sieve Size
Wt % of Particles Retained
#4
0
0
0
0
#5
0
0
0
0
#8
0
0
1
2
#20
3
4
12
19
#30
97
96
87
79
Non-Sintering Rating
2
1
2
2
In this case, Solflex 1216 (Goodyear Chemicals) a solution-SBR with a Mooney viscosity (ML 1+4 @ 100° C.) of 90 and a bound styrene content of 10% was used. The ratio of Sulflex 1216 to Carbon Black N650 was varied from 1:1.5 to 1:9, and the volume loading was adjusted in each case, as Table 23 shows. The mixing procedure was the same as in examples 1-4 of ROYALENE® 3275 with carbon black.
Table 30. Examples 89-91
TABLE 30
Example
89
90
91
SBR-1502:N-650
1:1.5
1:4
1:9
Volume Loading, %
57
45
33
Torque, m-gm
20
130
83
Sieve Size
Wt % of Particles Retained
#4
0
0
0
#5
0
0
0
#8
0
0
12
#20
5
9
13
#30
95
91
75
Non-Sintering Rating
2
1
1
In this series, the weight ratio of SBR-1502:N-650 was varied from 1:1.5 to 1:9, while the volume loading varied from 57% to 33%. The mixing procedure was the same as in examples 1-4. Example 91 shows that it is possible to use very high levels of carbon filler; i.e., 900 parts per 100 parts of SBR-1502, with excellent non-sintering rate of 1.
Example 92
In this case, blending trials were conducted with a ZSK-40 twin screw extruder, of Werner and Pfleiderer Co., with an experimental EPDM, ROYALENE® X70, having a Mooney viscosity (ML 4+1 @ 125° C.) of 62, an ethylene/propylene ratio of 70/30, and an ENB content of 2%, and N-650 carbon black to create a free flowing mixture.
The ROYALENE® X70 product was supplied as condensed bales which were cut into strips and granulated to feed the extruder via an Acrison feeder. The carbon black material was similarly fed to the extruder.
The extrusion process operating parameters varied in these trials included raw material feed rates and ratios, screw design, screw speed and barrel temperature, and screw profiles. The blend ratio of EPDM:carbon black was varied from 1:0.5 to 1:1.
Example 92, a typical case from these trials in a twin screw extruder, the free flowing associated composition of EPDM:N-650 ratio of 1:0.8, had a non-sintering rating of 3. This example demonstrates the ability to produce the products of this invention also in continuous screw extruders.
The present invention has been described in considerable detail with reference to the importance of the polymer:filler blend ratio and mixer volume loading, but other changes in the mixing procedure may impact on this invention. Anyone skilled in the art of rubber compounding can vary other parameters, such as, the type and size of the mixer, type of mixer rotors, mixing temperature, mixing time, type of grade of polymer, type of carbon black or other filler may also impact on the outcome of this invention. Therefore the spirit and scope of our claims should not be limited to the description of the preferred versions contained herein. | Disclosed are methods for the formation of a free flowing polymer/filler masterbatch powder, in which a polymer and filler are intimately mixed for a time and under shear conditions sufficient to convert the combination into a free flowing associated composition of polymer and filler. | 2 |
This is a continuation of Ser. No. 09/110,916 filed Jul. 6, 1998, now U.S. Pat. No. 6,082,608 which is a divisional of Ser. No. 08/716,687 filed Sep. 16, 1996 now U.S. Pat. No. 5,810,241.
1. FIELD OF THE INVENTION
The present invention, generally, relates to a method and apparatus for soldering small components automatically and, more particularly, to a new and improved component handling technique.
Prior U.S. Pat. No. 4,937,006 to Bickford et al. and assigned to the same Assignee as the present invention relates to a structure and method with which this invention is functional. Therefore, the description therein is incorporated by reference into the present description.
BACKGROUND OF THE INVENTION
Equipment and apparatus for handling microelectronic components during assembly, disassembly and rework phases must have an arrangement whereby the extremely small components are grasped for transporting and positioning accurately. In the past, such an arrangement has included a small nozzle-like structure with its larger end formed to fit the equipment or apparatus with which it is being used and its smaller end formed to receive the component to be handled.
In the microelectronic industry, there are dozens of these extremely small components varying in size from several millimeters down to a fraction of one millimeter, each requiring equipment with special tools in order to pick up, transport and position each component. The equipment to move and otherwise handle these extremely small components has been standardized with all adjustments needed to operate.
However, to avoid the necessity of making adjustments to this apparatus every time a different component is to be placed, it has become the standard practice to size the nozzle-like structure end to receive the component within the end surface, so that the apparatus can be adjusted to position the end surface accurately relative to that end. A component of a different size must have its own nozzle-like structure sized to receive it within that end, so it will not project out requiring another adjustment in order to place it accurately.
This practice has worked well for many years, but with the recent increase in technological advances, usage of this equipment has increased also, because of the increased need for building the circuits using smaller and smaller components. Requiring different component-receiving ends for each different component has become almost a nightmare, because of the need to correlate these ends and the components in a practical manner.
2. REVIEW OF THE PRIOR ART
U.S. Pat. No. 4,767,047 to Todd et al. describes a device for grasping a component by suction and heating the solder that holds it in place to soften the solder, whereby the component is removed from a substrate.
U.S. Pat. No. 4,844,325 to Nishiguchi et al. describes apparatus with a collet to grasp a semiconductor chip by the use of a vacuum pump and blowing an inert gas to heat the entire assembly.
U.S. Pat. No. 5,222,655 to Moretti et al. describes apparatus with an open-channeled member for holding an element by a vacuum and a heated gas system to heat the element for soldering.
It is well recognized that soldering involves the application of heat in order to melt the solder so that it adheres to surfaces for creating both electrical and physical connections. It is recognized also in the microelectronics industry particularly that all such applications of heat must be controlled to avoid damage.
OBJECTS AND SUMMARY OF THE INVENTION
It is a principal object of the present invention to provide a method and a device to permit an object to be grasped and retained for moving and positioning accurately in a cost effective manner.
Another object of the present invention is to provide a method and apparatus that avoids previous problems of having to correlate electrical objects with object-handling equipment.
Briefly, the present invention involves forming a nozzle that has a larger end and a smaller end, the larger end being to fit standard, object-handling equipment. The size and configuration of the smaller end is determined to receive a larger object. Forming an insert to be received within the smaller end opening of the nozzle. Forming the insert with an opening to receive a selected object to be handled. By changing inserts, objects of different sizes and configurations are handled readily.
These and other objects, features and advantages of the present invention will become more readily apparent from the following detailed description of the preferred embodiment.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a view in elevation illustrating the insert of the present invention in an operative relationship with a nozzle as an aid in describing the invention in more detail.
FIG. 2 is a plan view of the nozzle of FIG. 1 .
FIG. 3 is a plan view of one step in the process of fabricating an insert in accordance with the present invention.
FIG. 4 is a plan view of the insert fabricated according to the present invention with portions folded, as will be described in more detail hereinafter.
FIG. 5 is a view in elevation of the insert alone with portions folded as a further aid in the following description.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 of the drawings illustrates significant aspects of the invention, in that the numeral 10 identifies a nozzle having a larger end 11 and a smaller end 12 . The larger end 11 is formed to make the nozzle 10 readily attachable to a movable apparatus to position a component relative to a fixed-location, such as to position a chip for soldering to a circuit of a substrate.
The smaller end 12 of the nozzle 10 is larger than the size of a component that is to be handled, but an insert 13 is located over the smaller end 12 to make the opening appropriate for receiving a component. By “appropriate” is meant that such component must fit closely within the opening without binding.
It is the custom in the art to form the nozzle 10 with a small opening for the purpose of receiving a particular component closely without binding, and the component is received completely inside of the nozzle so that the equipment to which the nozzle 10 is attached need be adjusted only once for positioning the small end relative to its final location to deliver the component it carries. However, according to the present invention, it is the insert 13 that determines the opening size, which means that only one size of nozzle 10 is necessary for a range of component sizes.
The insert 13 is formed, according to the present invention, with a number of flaps 14 extending around the border and bent to fit the slope of the nozzle 10 . The friction between the flaps 14 against the slope of the nozzle is useful to retain the insert 13 over the opening in the smaller end 12 .
A negative pressure is created within the nozzle by a vacuum pump usually connected by means of a pipe 15 to draw and to retain a component within the small end of the nozzle. More details concerning the structure of the insert 13 , in accordance with the present invention, will be described presently hereinafter.
FIG. 2 of the drawings shows the nozzle 10 along the line 2 — 2 in FIG. 1 . The flaps 14 a and 14 b are visible since they are on the outside of the nozzle, and flaps 14 c and 14 d are illustrated in dotted lines since they are on the inside of the nozzle.
In accordance with the present invention, the insert 13 is formed from a single sheet, illustrated in FIG. 3 of the drawings, that is approximately 1.500 inches square. This dimension is only approximate because it may vary with different nozzle arrangement with which it is adapted to fit.
The important feature that the insert 13 represents is that the nozzle end 12 , seen in FIG. 2, is made with a larger opening than required for the smallest component, and the insert provides a way of obtaining the correct opening size, and shape, for each component to be picked up, transported and positioned correctly and accurately by equipment used for that purpose. Therefore, other and different ways may be provided by those skilled in this art for making this larger opening in a nozzle smaller as required for different sizes of components.
In FIG. 3, the four flaps are illustrated, and the opposite flaps 14 a and 14 b are identified more clearly, as are the opposite flaps 14 c and 14 d . While the length of the flaps 14 may vary and can be formed in accordance with various needs, it is found that a length of 1.5 inches from one edge 16 on the flap 14 a to the edge 17 on the flap 14 b is entirely satisfactory.
As described, supra, a central opening is formed in accordance with the dimensions of a particular component to be handled, such as a particular flip chip to be removed from a soldered position on a substrate and transported to a different location for reworking With the insert 10 of the invention, only the insert 13 is needed.
FIG. 4 of the drawings illustrates a view of the insert 13 alone as it is seen from the line 2 — 2 in FIG. 1 . That is, the two flaps 14 a and 14 b are extended over the outside surface of the nozzle while the two flaps 14 c and 14 d are on the inside of the nozzle and not visible.
FIG. 5 is a view of the insert 13 alone with the flaps 14 a , 14 b and 14 c being visible, and a view of the flap 14 d is blocked by the flap 14 c.
While the invention has been described in substantial detail with what is presently considered to be the most practical and the presently preferred embodiment, it is to be understood that the invention is not limited by the embodiment described, but rather, the invention is intended to include various modifications and the equivalent arrangements that are covered by the spirit and scope of the appended claims. Therefore, anyone skilled in this field should understand that all such alterations and changes are included within the scope of the following claims. | In an apparatus for soldering/desoldering components having a nozzle with larger and smaller ends, the larger end for attaching to an exhaust for drawing a vacuum and to a supply of heated gas for at least softening solder, an insert is attached at the smaller end of the nozzle to adjust the size of that opening for receiving each of a plurality of components, fitting different inserts to different sizes of components. | 1 |
TECHNICAL FIELD
[0001] The present invention is related to a product display for household fixtures and a method of merchandising, the display including a room mockup having various display elements representing the household fixtures included thereon.
BACKGROUND
[0002] Typically, household fixtures are sold in home improvement warehouses using full size models. The full size models simulate, for example, the appearance of bathrooms, kitchens, utility rooms, or wet bars to display the various household fixtures being sold. However, such full size models require relatively large amounts of retail space. Furthermore, alternate design features, such as choices for materials, colors, finishes, ornamentation, patterns, and textures, for the household fixtures are not readily displayed. Usually, the household fixtures included in a particular full size model are coordinated or aesthetically matched with one another. As such, to display household fixtures with alternate design features, it may be necessary to build other coordinated or aesthetically matched full size models.
[0003] As such, there is need for displaying various household fixtures in a relatively compact space while simultaneously displaying various alternate design features for the household fixtures.
SUMMARY
[0004] The present invention contemplates a product display provided to sell household fixtures including a display base, at least one wall provided adjacent the display base, and a room mockup provided on the display base adjacent the at least one wall, where the room mockup includes display elements representing the household fixtures.
BRIEF DESCRIPTION OF THE DRAWINGS
[0005] FIG. 1 is a perspective view of the product display according to the present invention.
[0006] FIG. 2 is a front elevational view of the product display depicted in FIG. 1 .
[0007] FIG. 3 is an enlarged view of a portion of FIG. 2 depicting a selection pallet.
DETAILED DESCRIPTION
[0008] The product display according to the present invention is generally indicated by the numeral 10 in the accompanying drawings. As discussed below, the product display 10 can be included in a retail setting to aid a consumer in selecting the configuration of household fixtures. The household fixtures can, for example, include cabinets including uppers, lowers, and cabinet hardware, countertops, crown molding, and flooring.
[0009] As shown in FIGS. 1 and 2 , the product display 10 includes three (3) room mockups generally indicated by the numerals 12 , 14 , and 16 . The room mockups 12 , 14 , and 16 include various display elements representing household fixtures that illustrate the available choices a consumer has when selecting the configuration of household fixtures to be installed in the consumer's home. As such, the room mockups 12 , 14 , and 16 serve as compact representations of, for example, bathrooms, kitchens, utility rooms, or wet bars, and illustrate the choices of design features (e.g., materials, colors, finishes, ornamentation, patterns, and textures) for the display elements available for selection by the consumer.
[0010] The product display 10 includes a platform 18 and an L-shaped wall 20 . The platform 18 includes a platform floor 22 and a riser 23 supporting the platform floor 22 , and the L-shaped wall 20 includes a first portion 24 and a second portion 25 . The platform 18 and the L-shaped wall 20 are constructed with enough structural rigidity to allow the product display 10 to be moved. As such, the product display 10 can be, as necessary, shipped to and repositioned in a retail setting without the need for significant onsite assembly.
[0011] The platform 18 and the L-shaped wall 20 define a display area 26 in which the room mockups 12 , 14 , and 16 are disposed. For example, each of the room mockups 12 , 14 , and 16 are positioned on the platform floor 22 adjacent the first wall portion 24 . As shown in FIGS. 1 and 2 , the room mockups 12 , 14 , and 16 can be canted at identical angles with respect to the first wall portion 24 .
[0012] The room mockups 12 , 14 , and 16 are framed by backboard walls 30 , 32 , and 34 , respectively. The backboard walls 30 , 32 , and 34 serve as a backdrop for the room mockups 12 , 14 , and 16 , respectively, and can be adorned with indicia and/or pictorials to enhance the visual appearance of the product display 10 . As shown best in FIG. 1 , the backboard walls 30 , 32 , and 34 can have concave shapes allowing the room mockups 12 , 14 , and 16 to be partially nested therein.
[0013] A cornice 36 can be provided adjacent the top of the product display 10 . As shown best in FIG. 1 , the cornice 36 extends from adjacent a vertical edge 38 of the first portion 24 to adjacent a vertical edge 39 of the second portion 25 of the L-shaped wall 20 . The cornice 36 serves to partially frame the display area 26 , and, like the backboard walls 30 , 32 , and 34 , can be adorned with indicia and/or pictorials to enhance the visual appearance of the product display 10 .
[0014] The cornice 36 can be used in concealing lighting fixtures (not shown) used to spotlight the room mockups 12 , 14 , and 16 . The lighting fixtures, like the above-discussed indicia and pictorials, can enhance the visual appearance of the product display 10 . The cornice 36 can also be used in supporting the room mockups 12 , 14 , and 16 . For example, horizontal support rods 27 extend from the cornice 36 to the L-shaped wall 20 . Furthermore, vertical support rods 28 extend from each of the room mockups 12 , 14 , and 16 to the horizontal support rods 27 . The horizontal support rods 27 and the vertical support rods 28 can be used to support the room mockups 12 , 14 , and 16 on the product display 10 .
[0015] As discussed above, each of the room mockups 12 , 14 , and 16 include various display elements representing various household fixtures. For example, as shown in FIGS. 1 and 2 , each of the room mockups 12 , 14 , and 16 include display elements such as flooring 40 , cabinet bases 42 , lower cabinet doors 44 , cabinet drawer facers 46 , countertops 48 , upper cabinet doors 50 , crown molding 52 , and cabinet hardware such as, for example, handles 54 and knobs 55 .
[0016] Each of the room mockups 12 , 14 , and 16 include various display elements having various alternate design features to illustrate the choices available to the consumer. The room mockups 12 , 14 , and 16 can each have different overall appearances, and include display elements with design features coordinated or aesthetically matched with one another. As discussed above, the various alternate design features include choices of materials, colors, finishes, ornamentation, patterns, and textures. As such, a consumer can select from the various alternate design features for the various display elements to determine the ultimate configuration of the household fixtures to be installed in the consumer's home.
[0017] For example, the choices of the design features associated with the flooring 40 include various materials, such as for example, woods, laminate, stone, tile, vinyl, and carpet, and the colors, the finishes, the patterns, and the textures associated therewith. The choices of the design features associated with the cabinet bases 42 , the lower cabinet doors 44 , the cabinet facers 46 , the upper cabinet doors 50 , and the crown molding 52 include various materials, such as for example, woods and laminates, and the colors, the finishes, the ornamentation, and the textures associated therewith. Furthermore, the choices of the design features associated with the countertops 48 include various materials, such as for example, composites, laminates, stone, and tile, and the colors, the finishes, the patterns, and the textures associated therewith. Also, the choices of the design features associated with the handles 54 and knobs 55 include various materials, such as for example, metals and woods, and the colors, the finishes, the ornamentation, and the textures associated therewith.
[0018] Various selection pallets 58 , 60 , and 62 are provided to further supplement the choices for the design features of the display elements included in the product display 10 . As shown in FIGS. 1 and 2 , the selection pallets 58 , 60 , and 62 are provided adjacent the room mockups 12 , 14 , and 16 , respectively, and can be attached to the upper cabinet doors 50 thereof.
[0019] The selection pallets 58 , 60 , and 62 include various placards attached thereto. For example, as best shown in FIG. 3 , indicia placards 64 and first, second, and third design placards 66 , 68 , and 70 can be provided on each of the selection pallets 58 , 60 , and 62 . The indicia placards 64 can include advertising copy and explanatory materials regarding the selection of various alternate design features for the display elements. Furthermore, the design placards 66 , 68 , and 70 can include samples providing additional alternate design features of the display elements.
[0020] The indicia placards 64 and the design placards 66 , 68 , and 70 can be permanently or removably attached to the selection pallets 58 , 60 , and 62 . For example, if removable, the design placards 66 , 68 , and 70 can be exchanged with other placards including further additional selections for the design features of the display elements.
[0021] The design placards 66 , 68 , and 70 can, for example, include samples 72 and 73 depicting additional alternate design features in the form of alternate material selections for the cabinet bases 42 , the lower cabinet doors 44 , the cabinet facers 46 , the upper cabinet doors 50 , and the crown molding 52 . The design placards 66 , 68 , and 70 can, for example, include samples 74 depicting additional alternate design features in the form of alternate material selections for the countertops 48 . Furthermore, the design placards 66 and 68 can, for example, include alternate handle selections 76 and alternate knob selections 77 for the handles 54 and knobs 55 , respectively.
[0022] Given the various alternate design features for the display elements included in the room mockups 12 , 14 , and 16 and the selection pallets 58 , 60 , and 62 , the consumer can conceptualize the appearance of alternate configurations for the household fixtures, and select the design features for the household fixtures that comport with his or her tastes.
[0023] While in accordance with the Patent Statutes, only the best mode and exemplary embodiments have been presented and described in detail, it is to be understood that the invention is not limited thereto or thereby. Furthermore, this Detailed Description merely describes exemplary embodiments and is not intended to limit the scope of the claims in any way. Indeed, the invention as described is broader than and unlimited by the described embodiments, and the terms used have their full ordinary meaning. | A product display for selling household fixtures includes a display base, at least one wall provided adjacent the base, and a room mockup provided on said display base adjacent said at least one wall. The room mockup includes various display elements representing the household fixtures, and at least one of the display elements included has a set of alternate design features associated therewith. A selection pallet can be provided adjacent the room mockup. The selection pallet includes samples of alternate design features for the display elements. | 0 |
CROSS-REFERENCE TO RELATED APPLICATION
This U.S. patent application claims the benefit of PCT application serial no. PCT/US2011/046992, filed on Aug. 9, 2011, which claims the benefit of U.S. provisional application Ser. No. 61/372,269, filed on Aug. 10, 2010. Each of these documents is hereby incorporated by reference in its entirety.
TECHNICAL FIELD OF THE INVENTION
The present invention provides novel methods for synthesizing PPARγ sparing compounds, e.g., thiazolidinediones, that are useful for preventing and/or treating metabolic disorders such as diabetes, obesity, hypertension, dyslipidemia, and inflammatory diseases.
BACKGROUND OF THE INVENTION
Over the past several decades, scientists have postulated that PPARγ is the generally accepted site of action for insulin sensitizing thiazolidinedione compounds.
Peroxisome Proliferator Activated Receptors (PPARs) are members of the nuclear hormone receptor super-family, which are ligand-activated transcription factors regulating gene expression. PPARs have been implicated in autoimmune diseases and other diseases, i.e., diabetes mellitus, cardiovascular and gastrointestinal disease, and Alzheimer's disease.
PPARγ is a key regulator of adipocyte differentiation and lipid metabolism. PPARγ is also found in other cell types including fibroblasts, myocytes, breast cells, human bone-marrow precursors, and macrophages/monocytes. In addition, PPARγ has been shown in macrophage foam cells in atherosclerotic plaques.
Thiazolidinediones, such as pioglitazone, developed originally for the treatment of type-2 diabetes, generally exhibit high affinity as PPARγ ligands. The finding that thiazolidinediones might mediate their therapeutic effects through direct interactions with PPARγ helped to establish the concept that PPARγ is a key regulator of glucose and lipid homeostasis. However, compounds that involve the activation of PPARγ, such as pioglitazone, also trigger sodium reabsorption and other unpleasant side effects.
SUMMARY OF THE INVENTION
In general, the invention relates to methods of synthesizing compounds that have reduced binding and activation of the nuclear transcription factor PPARγ when compared with high affinity PPARγ ligands such as pioglitazone and rosiglitazone. These novel methods are scalable for industrial production and employ safer, more stable, and/or less costly starting materials and process conditions.
Compounds exhibiting PPARγ activity induce transcription of genes that favor sodium reabsorption. Advantageously, the compounds produced by the syntheses of this invention have reduced binding or activation of the nuclear transcription factor PPARγ when compared with traditional high affinity PPARγ ligands (e.g., pioglitazone or rosiglitazone), and therefore produce fewer or diminished side effects (e.g., reduced augmentation of sodium reabsorption) that are associated with traditional high affinity PPARγ ligands, and are therefore more useful in treating hypertension, dyslipidemia, diabetes, and inflammatory diseases. Moreover, the reduced PPARγ binding and reduced activity exhibited by these compounds, as compared with traditional high affinity PPARγ ligands, are particularly useful for treating hypertension, diabetes, dyslipidemia, and inflammatory diseases both as single agents and in combination with other classes of antihypertensive agents. As hypertension and inflammatory diseases pose major risk factors in the onset of diabetes and pre-diabetes, these compounds are also useful for the treatment and prevention of diabetes and other inflammatory diseases. In fact, compounds synthesized by the present invention may induce remission of the symptoms of diabetes in a human patient.
One aspect of the present invention provides a novel synthesis for generating thiazolidine compounds that are useful for the treatment of metabolic disorders. This synthetic method is useful for preparing a compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein each of R 1 and R 2 is independently selected from H, halo, aliphatic (e.g., C 1-6 alkyl), or alkoxy (e.g., C 1-6 alkoxy), wherein the aliphatic or alkoxy is optionally substituted with 1-3 of halo; comprising the step of converting a compound of Formula 2A into a compound of Formula I
wherein R 3 is hydrogen or an optionally substituted C 1-6 alkyl. In some embodiments, the compound of Formula 2A undergoes hydrolysis to generate a compound of Formula I. In some examples, the compound of Formula 2A is treated with an acid to generate the compound of Formula I. In other examples, the compound of Formula 2A is treated with an acid and heat to generate a compound of Formula I.
In some embodiments, R 3 is methyl, ethyl, propyl, isopropyl, butyl, or tert-butyl, each of which is optionally substituted. In other embodiments, R 3 is methyl, ethyl, propyl, isopropyl, butyl, or tert-butyl, each of which is unsubstituted. And, in some embodiments, R 3 is hydrogen.
Some embodiments further comprise reacting a compound of Formula 3A with a compound of Formula 4A:
wherein X 1 is a leaving group, to generate the compound of Formula 2A. In some embodiments, the compound of Formula 4A comprises
In other embodiments, the compound of Formula 4A comprises
And in some embodiments, the compound of Formula 4A comprises
Some embodiments further comprise converting a compound of Formula 5A
wherein X 1 is a leaving group, to a compound of Formula 4A. In some embodiments, X 1 is a halo (e.g., Cl or Br) or triflyl group.
In some embodiments, the compound of Formula 5A comprises
wherein X 1 is Cl or Br.
Some embodiments further comprise converting a compound of Formula 6A
to a compound of Formula 5A. For example, the compound of Formula 6A undergoes halogenation to generate a compound of Formula 5A.
In some embodiments, the compound of Formula 6A comprises
wherein R 1 is selected from a C 1-6 alkyl or C 1-6 alkoxy, either of which is optionally substituted with 1-3 halo, and R 2 is —H or halo.
In some embodiments, R 1 is a C 1-6 alkyl optionally substituted with 1-3 halo. For example, R 1 is selected from methyl, ethyl, or propyl, any of which is optionally substituted with 1-3 halo.
In some embodiments, the compound of Formula 6A comprises
Some embodiments further comprise reacting the compound
with the compound
under condensation conditions to form a compound of Formula 3B
and reducing the compound of Formula 3B to generate the compound of Formula 3A.
Another aspect of the present invention provides compounds that are useful in the methods of the present invention. One embodiment provides a compound of Formula 10A, 10B, or 10C
wherein R 1 is halo, C 1-6 alkyl optionally substituted with 1-3 halo, or C 1-6 alkoxy optionally substituted with 1-3 halo; R 3 is hydrogen or unsubstituted C 1-6 alkyl (e.g., unsubstituted C 1-4 alkyl); and X A is a leaving group (e.g., halo or triflyl) or hydrogen.
Another aspect of the present invention provides a compound of Formula 10D, 10E, or 10F
wherein R 1 and X A are defined above.
In several embodiments, R 3 of Formula 10A, 10B, or 10C is hydrogen. In other embodiments, R 3 of Formula 10A, 10B, or 10C is methyl, ethyl, propyl, isopropyl, butyl, or tert-butyl, each of which is unsubstituted.
Another aspect of the present invention provides a compound Formula 11A-11M.
wherein X A is a leaving group or hydrogen and R 3 is hydrogen or C 1-3 unsubstituted alkyl.
In some embodiments, X A is a leaving group selected from —Br, —Cl, —I, —OMs, —OTs, —OTf, —OBs, —ONs, —O-tresylate, or —OPO(OR 4 ) 2 , wherein each R 4 is independently C 1-4 alkyl or two of R 4 together with the oxygen and phosphorous atoms to which they are attached form a 5-7 membered ring. In other embodiments, X A is hydrogen.
Another aspect of the present invention provides a compound of Formula 2A
wherein each of R 1 , R 2 , and R 3 is defined above. For example, in one embodiment, the compound of Formula 2A comprises
And, another aspect of the present invention provides a compound selected from
wherein R 3 is defined above.
DETAILED DESCRIPTION
The present invention provides novel methods for preparing thiazolidinedione compounds having reduced PPARγ activity and compounds useful in these methods.
As used herein, the following definitions shall apply unless otherwise indicated.
I. DEFINITIONS
For purposes of this invention, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75th Ed. Additionally, general principles of organic chemistry are described in “Organic Chemistry”, Thomas Sorrell, University Science Books, Sausalito: 1999, and “March's Advanced Organic Chemistry”, 5th Ed., Ed.: Smith, M. B. and March, J., John Wiley & Sons, New York: 2001, the entire contents of which are hereby incorporated by reference.
As described herein, “protecting group” refers to a moiety or functionality that is introduced into a molecule by chemical modification of a functional group in order to obtain chemoselectivity in a subsequent chemical reaction. Standard protecting groups are provided in Greene and Wuts: “Greene's Protective Groups in Organic Synthesis” 4th Ed, Wuts, P. G. M. and Greene, T. W., Wiley-Interscience, New York: 2006.
As described herein, compounds of the invention may optionally be substituted with one or more substituents, such as are illustrated generally above, or as exemplified by particular classes, subclasses, and species of the invention.
As used herein, the term “hydroxyl” or “hydroxy” refers to an —OH moiety.
As used herein the term “aliphatic” encompasses the terms alkyl, alkenyl, alkynyl, each of which being optionally substituted as set forth below.
As used herein, an “alkyl” group refers to a saturated aliphatic hydrocarbon group containing 1-12 (e.g., 1-8, 1-6, or 1-4) carbon atoms. An alkyl group can be straight or branched. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-heptyl, or 2-ethylhexyl. An alkyl group can be substituted (i.e., optionally substituted) with one or more substituents such as halo, phospho, cycloaliphatic [e.g., cycloalkyl or cycloalkenyl], heterocycloaliphatic [e.g., heterocycloalkyl or heterocycloalkenyl], aryl, heteroaryl, alkoxy, aroyl, heteroaroyl, acyl [e.g., (aliphatic)carbonyl, (cycloaliphatic)carbonyl, or (heterocycloaliphatic)carbonyl], nitro, cyano, amido [e.g., (cycloalkylalkyl)carbonylamino, arylcarbonylamino, aralkylcarbonylamino, (heterocycloalkyl)carbonylamino, (heterocycloalkylalkyl)carbonylamino, heteroarylcarbonylamino, heteroaralkylcarbonylamino alkylaminocarbonyl, cycloalkylaminocarbonyl, heterocycloalkylaminocarbonyl, arylaminocarbonyl, or heteroarylaminocarbonyl], amino [e.g., aliphaticamino, cycloaliphaticamino, or heterocycloaliphaticamino], sulfonyl [e.g., aliphatic-SO 2 —], sulfinyl, sulfanyl, sulfoxy, urea, thiourea, sulfamoyl, sulfamide, oxo, carboxy, carbamoyl, cycloaliphaticoxy, heterocycloaliphaticoxy, aryloxy, heteroaryloxy, aralkyloxy, heteroarylalkoxy, alkoxycarbonyl, alkylcarbonyloxy, or hydroxy. Without limitation, some examples of substituted alkyls include carboxyalkyl (such as HOOC-alkyl, alkoxycarbonylalkyl, and alkylcarbonyloxyalkyl), cyanoalkyl, hydroxyalkyl, alkoxyalkyl, acylalkyl, aralkyl, (alkoxyaryl)alkyl, (sulfonylamino)alkyl (such as (alkyl-SO 2 -amino)alkyl), aminoalkyl, amidoalkyl, (cycloaliphatic)alkyl, or haloalkyl.
As used herein, an “alkenyl” group refers to an aliphatic carbon group that contains 2-8 (e.g., 2-12, 2-6, or 2-4) carbon atoms and at least one double bond. Like an alkyl group, an alkenyl group can be straight or branched. Examples of an alkenyl group include, but are not limited to allyl, isoprenyl, 2-butenyl, and 2-hexenyl. An alkenyl group can be optionally substituted with one or more substituents such as halo, phospho, cycloaliphatic [e.g., cycloalkyl or cycloalkenyl], heterocycloaliphatic [e.g., heterocycloalkyl or heterocycloalkenyl], aryl, heteroaryl, alkoxy, aroyl, heteroaroyl, acyl [e.g., (aliphatic)carbonyl, (cycloaliphatic)carbonyl, or (heterocycloaliphatic)carbonyl], nitro, cyano, amido [e.g., (cycloalkylalkyl)carbonylamino, arylcarbonylamino, aralkylcarbonylamino, (heterocycloalkyl)carbonylamino, (heterocycloalkylalkyl)carbonylamino, heteroarylcarbonylamino, heteroaralkylcarbonylamino alkylaminocarbonyl, cycloalkylaminocarbonyl, heterocycloalkylaminocarbonyl, arylaminocarbonyl, or heteroarylaminocarbonyl], amino [e.g., aliphaticamino, cycloaliphaticamino, heterocycloaliphaticamino, or aliphaticsulfonylamino], sulfonyl [e.g., alkyl-SO 2 —, cycloaliphatic-SO 2 —, or aryl-SO 2 —], sulfinyl, sulfanyl, sulfoxy, urea, thiourea, sulfamoyl, sulfamide, oxo, carboxy, carbamoyl, cycloaliphaticoxy, heterocycloaliphaticoxy, aryloxy, heteroaryloxy, aralkyloxy, heteroaralkoxy, alkoxycarbonyl, alkylcarbonyloxy, or hydroxy. Without limitation, some examples of substituted alkenyls include cyanoalkenyl, alkoxyalkenyl, acylalkenyl, hydroxyalkenyl, aralkenyl, (alkoxyaryl)alkenyl, (sulfonylamino)alkenyl (such as (alkyl-SO 2 -amino)alkenyl), aminoalkenyl, amidoalkenyl, (cycloaliphatic)alkenyl, or haloalkenyl.
As used herein, an “alkynyl” group refers to an aliphatic carbon group that contains 2-8 (e.g., 2-12, 2-6, or 2-4) carbon atoms and has at least one triple bond. An alkynyl group can be straight or branched. Examples of an alkynyl group include, but are not limited to, propargyl and butynyl. An alkynyl group can be optionally substituted with one or more substituents such as aroyl, heteroaroyl, alkoxy, cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, aralkyloxy, nitro, carboxy, cyano, halo, hydroxy, sulfo, mercapto, sulfanyl [e.g., aliphaticsulfanyl or cycloaliphaticsulfanyl], sulfinyl [e.g., aliphaticsulfinyl or cycloaliphaticsulfinyl], sulfonyl [e.g., aliphatic-SO 2 —, aliphaticamino-SO 2 —, or cycloaliphatic-SO 2 —], amido [e.g., aminocarbonyl, alkylaminocarbonyl, alkylcarbonylamino, cycloalkylaminocarbonyl, heterocycloalkylaminocarbonyl, cycloalkylcarbonylamino, arylaminocarbonyl, arylcarbonylamino, aralkylcarbonylamino, (heterocycloalkyl)carbonylamino, (cycloalkylalkyl)carbonylamino, heteroaralkylcarbonylamino, heteroarylcarbonylamino or heteroarylaminocarbonyl], urea, thiourea, sulfamoyl, sulfamide, alkoxycarbonyl, alkylcarbonyloxy, cycloaliphatic, heterocycloaliphatic, aryl, heteroaryl, acyl [e.g., (cycloaliphatic)carbonyl or (heterocycloaliphatic)carbonyl], amino [e.g., aliphaticamino], sulfoxy, oxo, carboxy, carbamoyl, (cycloaliphatic)oxy, (heterocycloaliphatic)oxy, or (heteroaryl)alkoxy.
As used herein, an “amido” encompasses both “aminocarbonyl” and “carbonylamino”. These terms when used alone or in connection with another group refer to an amido group such as —N(R X )—C(O)—R Y or —C(O)—N(R X ) 2 , when used terminally, and —C(O)—N(R X )— or —N(R X )—C(O)— when used internally, wherein R X and R Y can be aliphatic, cycloaliphatic, aryl, araliphatic, heterocycloaliphatic, heteroaryl or heteroaraliphatic. Examples of amido groups include alkylamido (such as alkylcarbonylamino or alkylaminocarbonyl), (heterocycloaliphatic)amido, (heteroaralkyl)amido, (heteroaryl)amido, (heterocycloalkyl)alkylamido, arylamido, aralkylamido, (cycloalkyl)alkylamido, or cycloalkylamido.
As used herein, an “amino” group refers to —NR X R Y wherein each of R X and R Y is independently hydrogen, aliphatic, cycloaliphatic, (cycloaliphatic)aliphatic, aryl, araliphatic, heterocycloaliphatic, (heterocycloaliphatic)aliphatic, heteroaryl, carboxy, sulfanyl, sulfinyl, sulfonyl, (aliphatic)carbonyl, (cycloaliphatic)carbonyl, ((cycloaliphatic)aliphatic)carbonyl, arylcarbonyl, (araliphatic)carbonyl, (heterocycloaliphatic)carbonyl, ((heterocycloaliphatic)aliphatic)carbonyl, (heteroaryl)carbonyl, or (heteroaraliphatic)carbonyl, each of which being defined herein and being optionally substituted. Examples of amino groups include alkylamino, dialkylamino, or arylamino. When the term “amino” is not the terminal group (e.g., alkylcarbonylamino), it is represented by —NR X —, where R X has the same meaning as defined above.
As used herein, an “aryl” group used alone or as part of a larger moiety as in “aralkyl”, “aralkoxy”, or “aryloxyalkyl” refers to monocyclic (e.g., phenyl); bicyclic (e.g., indenyl, naphthalenyl, tetrahydronaphthyl, tetrahydroindenyl); and tricyclic (e.g., fluorenyl tetrahydrofluorenyl, or tetrahydroanthracenyl, anthracenyl) ring systems in which the monocyclic ring system is aromatic or at least one of the rings in a bicyclic or tricyclic ring system is aromatic. The bicyclic and tricyclic groups include benzofused 2-3 membered carbocyclic rings. For example, a benzofused group includes phenyl fused with two or more C 4-8 carbocyclic moieties. An aryl is optionally substituted with one or more substituents including aliphatic [e.g., alkyl, alkenyl, or alkynyl]; cycloaliphatic; (cycloaliphatic)aliphatic; heterocycloaliphatic; (heterocycloaliphatic)aliphatic; aryl; heteroaryl; alkoxy; (cycloaliphatic)oxy; (heterocycloaliphatic)oxy; aryloxy; heteroaryloxy; (araliphatic)oxy; (heteroaraliphatic)oxy; aroyl; heteroaroyl; amino; oxo (on a non-aromatic carbocyclic ring of a benzofused bicyclic or tricyclic aryl); nitro; carboxy; amido; acyl [e.g., (aliphatic)carbonyl; (cycloaliphatic)carbonyl; ((cycloaliphatic)aliphatic)carbonyl; (araliphatic)carbonyl; (heterocycloaliphatic)carbonyl; ((heterocycloaliphatic)aliphatic)carbonyl; or (heteroaraliphatic)carbonyl]; sulfonyl [e.g., aliphatic-SO 2 — or amino-SO 2 —]; sulfinyl [e.g., aliphatic-S(O)— or cycloaliphatic-S(O)—]; sulfanyl [e.g., aliphatic-S-]; cyano; halo; hydroxy; mercapto; sulfoxy; urea; thiourea; sulfamoyl; sulfamide; or carbamoyl. Alternatively, an aryl can be unsubstituted.
Non-limiting examples of substituted aryls include haloaryl [e.g., mono-, di (such as p,m-dihaloaryl), and (trihalo)aryl]; (carboxy)aryl [e.g., (alkoxycarbonyl)aryl, ((aralkyl)carbonyloxy)aryl, and (alkoxycarbonyl)aryl]; (amido)aryl [e.g., (aminocarbonyl)aryl, (((alkylamino)alkyl)aminocarbonyl)aryl, (alkylcarbonyl)aminoaryl, (arylaminocarbonyl)aryl, and (((heteroaryl)amino)carbonyl)aryl]; aminoaryl [e.g., ((alkylsulfonyl)amino)aryl or ((dialkyl)amino)aryl]; (cyanoalkyl)aryl; (alkoxy)aryl; (sulfamoyl)aryl [e.g., (aminosulfonyl)aryl]; (alkylsulfonyl)aryl; (cyano)aryl; (hydroxyalkyl)aryl; ((alkoxy)alkyl)aryl; (hydroxy)aryl, ((carboxy)alkyl)aryl; (((dialkyl)amino)alkyl)aryl; (nitroalkyl)aryl; (((alkylsulfonyl)amino)alkyl)aryl; ((heterocycloaliphatic)carbonyl)aryl; ((alkylsulfonyl)alkyl)aryl; (cyanoalkyl)aryl; (hydroxyalkyl)aryl; (alkylcarbonyl)aryl; alkylaryl; (trihaloalkyl)aryl; p-amino-m-alkoxycarbonylaryl; p-amino-m-cyanoaryl; p-halo-m-aminoaryl; or (m-(heterocycloaliphatic)-o-(alkyl))aryl.
As used herein, an “araliphatic” such as an “aralkyl” group refers to an aliphatic group (e.g., a C 1-4 alkyl group) that is substituted with an aryl group. “Aliphatic,” “alkyl,” and “aryl” are defined herein. An example of an araliphatic such as an aralkyl group is benzyl.
As used herein, an “aralkyl” group refers to an alkyl group (e.g., a C 1-4 alkyl group) that is substituted with an aryl group. Both “alkyl” and “aryl” have been defined above. An example of an aralkyl group is benzyl. An aralkyl is optionally substituted with one or more substituents such as aliphatic [e.g., alkyl, alkenyl, or alkynyl, including carboxyalkyl, hydroxyalkyl, or haloalkyl such as trifluoromethyl], cycloaliphatic [e.g., cycloalkyl or cycloalkenyl], (cycloalkyl)alkyl, heterocycloalkyl, (heterocycloalkyl)alkyl, aryl, heteroaryl, alkoxy, cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, aralkyloxy, heteroaralkyloxy, aroyl, heteroaroyl, nitro, carboxy, alkoxycarbonyl, alkylcarbonyloxy, amido [e.g., aminocarbonyl, alkylcarbonylamino, cycloalkylcarbonylamino, (cycloalkylalkyl)carbonylamino, arylcarbonylamino, aralkylcarbonylamino, (heterocycloalkyl)carbonylamino, (heterocycloalkylalkyl)carbonylamino, heteroarylcarbonylamino, or heteroaralkylcarbonylamino], cyano, halo, hydroxy, acyl, mercapto, alkylsulfanyl, sulfoxy, urea, thiourea, sulfamoyl, sulfamide, oxo, or carbamoyl.
As used herein, a “bicyclic ring system” includes 8-12 (e.g., 9, 10, or 11) membered structures that form two rings, wherein the two rings have at least one atom in common (e.g., 2 atoms in common). Bicyclic ring systems include bicycloaliphatics (e.g., bicycloalkyl or bicycloalkenyl), bicycloheteroaliphatics, bicyclic aryls, and bicyclic heteroaryls.
As used herein, a “cycloaliphatic” group encompasses a “cycloalkyl” group and a “cycloalkenyl” group, each of which being optionally substituted as set forth below.
As used herein, a “cycloalkyl” group refers to a saturated carbocyclic mono- or bicyclic (fused or bridged) ring of 3-10 (e.g., 5-10) carbon atoms. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, norbornyl, cubyl, octahydro-indenyl, decahydro-naphthyl, bicyclo[3.2.1]octyl, bicyclo[2.2.2]octyl, bicyclo[3.3.1]nonyl, bicyclo[3.3.2.]decyl, bicyclo[2.2.2]octyl, adamantyl, or ((aminocarbonyl)cycloalkyl)cycloalkyl.
A “cycloalkenyl” group, as used herein, refers to a non-aromatic carbocyclic ring of 3-10 (e.g., 4-8) carbon atoms having one or more double bonds. Examples of cycloalkenyl groups include cyclopentenyl, 1,4-cyclohexa-di-enyl, cycloheptenyl, cyclooctenyl, hexahydro-indenyl, octahydro-naphthyl, cyclohexenyl, cyclopentenyl, bicyclo[2.2.2]octenyl, or bicyclo[3.3.1]nonenyl.
A cycloalkyl or cycloalkenyl group can be optionally substituted with one or more substituents such as phosphor, aliphatic [e.g., alkyl, alkenyl, or alkynyl], cycloaliphatic, (cycloaliphatic) aliphatic, heterocycloaliphatic, (heterocycloaliphatic) aliphatic, aryl, heteroaryl, alkoxy, (cycloaliphatic)oxy, (heterocycloaliphatic)oxy, aryloxy, heteroaryloxy, (araliphatic)oxy, (heteroaraliphatic)oxy, aroyl, heteroaroyl, amino, amido [e.g., (aliphatic)carbonylamino, (cycloaliphatic)carbonylamino, ((cycloaliphatic)aliphatic)carbonylamino, (aryl)carbonylamino, (araliphatic)carbonylamino, (heterocycloaliphatic)carbonylamino, ((heterocycloaliphatic)aliphatic)carbonylamino, (heteroaryl)carbonylamino, or (heteroaraliphatic)carbonylamino], nitro, carboxy [e.g., HOOC—, alkoxycarbonyl, or alkylcarbonyloxy], acyl [e.g., (cycloaliphatic)carbonyl, ((cycloaliphatic) aliphatic)carbonyl, (araliphatic)carbonyl, (heterocycloaliphatic)carbonyl, ((heterocycloaliphatic)aliphatic)carbonyl, or (heteroaraliphatic)carbonyl], cyano, halo, hydroxy, mercapto, sulfonyl [e.g., alkyl-SO 2 — and aryl-SO 2 —], sulfinyl [e.g., alkyl-S(O)—], sulfanyl [e.g., alkyl-S—], sulfoxy, urea, thiourea, sulfamoyl, sulfamide, oxo, or carbamoyl.
As used herein, the term “heterocycloaliphatic” encompasses heterocycloalkyl groups and heterocycloalkenyl groups, each of which being optionally substituted as set forth below.
As used herein, a “heterocycloalkyl” group refers to a 3-10 membered mono- or bicylic (fused or bridged) (e.g., 5- to 10-membered mono- or bicyclic) saturated ring structure, in which one or more of the ring atoms is a heteroatom (e.g., N, O, S, or combinations thereof). Examples of a heterocycloalkyl group include piperidyl, piperazyl, tetrahydropyranyl, tetrahydrofuryl, 1,4-dioxolanyl, 1,4-dithianyl, 1,3-dioxolanyl, oxazolidyl, isoxazolidyl, morpholinyl, thiomorpholyl, octahydrobenzofuryl, octahydrochromenyl, octahydrothiochromenyl, octahydroindolyl, octahydropyrindinyl, decahydroquinolinyl, octahydrobenzo[b]thiopheneyl, 2-oxa-bicyclo[2.2.2]octyl, 1-aza-bicyclo[2.2.2]octyl, 3-aza-bicyclo[3.2.1]octyl, and 2,6-dioxa-tricyclo[3.3.1.0 3,7 ]nonyl. A monocyclic heterocycloalkyl group can be fused with a phenyl moiety to form structures, such as tetrahydroisoquinoline, which would be categorized as heteroaryls.
A “heterocycloalkenyl” group, as used herein, refers to a mono- or bicylic (e.g., 5- to 10-membered mono- or bicyclic) non-aromatic ring structure having one or more double bonds, and wherein one or more of the ring atoms is a heteroatom (e.g., N, O, or S). Monocyclic and bicyclic heterocycloaliphatics are numbered according to standard chemical nomenclature.
A heterocycloalkyl or heterocycloalkenyl group can be optionally substituted with one or more substituents such as phosphor, aliphatic [e.g., alkyl, alkenyl, or alkynyl], cycloaliphatic, (cycloaliphatic)aliphatic, heterocycloaliphatic, (heterocycloaliphatic)aliphatic, aryl, heteroaryl, alkoxy, (cycloaliphatic)oxy, (heterocycloaliphatic)oxy, aryloxy, heteroaryloxy, (araliphatic)oxy, (heteroaraliphatic)oxy, aroyl, heteroaroyl, amino, amido [e.g., (aliphatic)carbonylamino, (cycloaliphatic)carbonylamino, ((cycloaliphatic) aliphatic)carbonylamino, (aryl)carbonylamino, (araliphatic)carbonylamino, (heterocycloaliphatic)carbonylamino, ((heterocycloaliphatic) aliphatic)carbonylamino, (heteroaryl)carbonylamino, or (heteroaraliphatic)carbonylamino], nitro, carboxy [e.g., HOOC—, alkoxycarbonyl, or alkylcarbonyloxy], acyl [e.g., (cycloaliphatic)carbonyl, ((cycloaliphatic) aliphatic)carbonyl, (araliphatic)carbonyl, (heterocycloaliphatic)carbonyl, ((heterocycloaliphatic)aliphatic)carbonyl, or (heteroaraliphatic)carbonyl], nitro, cyano, halo, hydroxy, mercapto, sulfonyl [e.g., alkylsulfonyl or arylsulfonyl], sulfinyl [e.g., alkylsulfinyl], sulfanyl [e.g., alkylsulfanyl], sulfoxy, urea, thiourea, sulfamoyl, sulfamide, oxo, or carbamoyl.
A “heteroaryl” group, as used herein, refers to a monocyclic, bicyclic, or tricyclic ring system having 4 to 15 ring atoms wherein one or more of the ring atoms is a heteroatom (e.g., N, O, S, or combinations thereof) and in which the monocyclic ring system is aromatic or at least one of the rings in the bicyclic or tricyclic ring systems is aromatic. A heteroaryl group includes a benzofused ring system having 2 to 3 rings. For example, a benzofused group includes benzo fused with one or two 4 to 8 membered heterocycloaliphatic moieties (e.g., indolizyl, indolyl, isoindolyl, 3H-indolyl, indolinyl, benzo[b]furyl, benzo[b]thiophenyl, quinolinyl, or isoquinolinyl). Some examples of heteroaryl are pyridyl, 1H-indazolyl, furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, tetrazolyl, benzofuryl, isoquinolinyl, benzthiazolyl, xanthene, thioxanthene, phenothiazine, dihydroindole, benzo[1,3]dioxole, benzo[b]furyl, benzo[b]thiophenyl, indazolyl, benzimidazolyl, benzthiazolyl, puryl, cinnolyl, quinolyl, quinazolyl, cinnolyl, phthalazyl, quinazolyl, quinoxalyl, isoquinolyl, 4H-quinolizyl, benzo-1,2,5-thiadiazolyl, or 1,8-naphthyridyl.
Without limitation, monocyclic heteroaryls include furyl, thiophenyl, 2H-pyrrolyl, pyrrolyl, oxazolyl, thazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, 1,3,4-thiadiazolyl, 2H-pyranyl, 4-H-pranyl, pyridyl, pyridazyl, pyrimidyl, pyrazolyl, pyrazyl, or 1,3,5-triazyl. Monocyclic heteroaryls are numbered according to standard chemical nomenclature.
Without limitation, bicyclic heteroaryls include indolizyl, indolyl, isoindolyl, 3H-indolyl, indolinyl, benzo[b]furyl, benzo[b]thiophenyl, quinolinyl, isoquinolinyl, indolizyl, isoindolyl, indolyl, benzo[b]furyl, bexo[b]thiophenyl, indazolyl, benzimidazyl, benzthiazolyl, purinyl, 4H-quinolizyl, quinolyl, isoquinolyl, cinnolyl, phthalazyl, quinazolyl, quinoxalyl, 1,8-naphthyridyl, or pteridyl. Bicyclic heteroaryls are numbered according to standard chemical nomenclature.
A heteroaryl is optionally substituted with one or more substituents such as aliphatic [e.g., alkyl, alkenyl, or alkynyl]; cycloaliphatic; (cycloaliphatic)aliphatic; heterocycloaliphatic; (heterocycloaliphatic)aliphatic; aryl; heteroaryl; alkoxy; (cycloaliphatic)oxy; (heterocycloaliphatic)oxy; aryloxy; heteroaryloxy; (araliphatic)oxy; (heteroaraliphatic)oxy; aroyl; heteroaroyl; amino; oxo (on a non-aromatic carbocyclic or heterocyclic ring of a bicyclic or tricyclic heteroaryl); carboxy; amido; acyl [e.g., aliphaticcarbonyl; (cycloaliphatic)carbonyl; ((cycloaliphatic)aliphatic)carbonyl; (araliphatic)carbonyl; (heterocycloaliphatic)carbonyl; ((heterocycloaliphatic)aliphatic)carbonyl; or (heteroaraliphatic)carbonyl]; sulfonyl [e.g., aliphaticsulfonyl or aminosulfonyl]; sulfinyl [e.g., aliphaticsulfinyl]; sulfanyl [e.g., aliphaticsulfanyl]; nitro; cyano; halo; hydroxy; mercapto; sulfoxy; urea; thiourea; sulfamoyl; sulfamide; or carbamoyl. Alternatively, a heteroaryl can be unsubstituted.
Non-limiting examples of substituted heteroaryls include (halo)heteroaryl [e.g., mono- and di-(halo)heteroaryl]; (carboxy)heteroaryl [e.g., (alkoxycarbonyl)heteroaryl]; cyanoheteroaryl; aminoheteroaryl [e.g., ((alkylsulfonyl)amino)heteroaryl and ((dialkyl)amino)heteroaryl]; (amido)heteroaryl [e.g., aminocarbonylheteroaryl, ((alkylcarbonyl)amino)heteroaryl, ((((alkyl)amino)alkyl)aminocarbonyl)heteroaryl, (((heteroaryl)amino)carbonyl)heteroaryl, ((heterocycloaliphatic)carbonyl)heteroaryl, and ((alkylcarbonyl)amino)heteroaryl]; (cyanoalkyl)heteroaryl; (alkoxy)heteroaryl; (sulfamoyl)heteroaryl [e.g., (aminosulfonyl)heteroaryl]; (sulfonyl)heteroaryl [e.g., (alkylsulfonyl)heteroaryl]; (hydroxyalkyl)heteroaryl; (alkoxyalkyl)heteroaryl; (hydroxy)heteroaryl; ((carboxy)alkyl)heteroaryl; (((dialkyl)amino)alkyl]heteroaryl; (heterocycloaliphatic)heteroaryl; (cycloaliphatic)heteroaryl; (nitroalkyl)heteroaryl; (((alkylsulfonyl)amino)alkyl)heteroaryl; ((alkylsulfonyl)alkyl)heteroaryl; (cyanoalkyl)heteroaryl; (acyl)heteroaryl [e.g., (alkylcarbonyl)heteroaryl]; (alkyl)heteroaryl; or (haloalkyl)heteroaryl [e.g., trihaloalkylheteroaryl].
A “heteroaraliphatic” (such as a heteroaralkyl group) as used herein, refers to an aliphatic group (e.g., a C 1-4 alkyl group) that is substituted with a heteroaryl group. “Aliphatic”, “alkyl”, and “heteroaryl” have been defined above.
A “heteroaralkyl” group, as used herein, refers to an alkyl group (e.g., a C 1-4 alkyl group) that is substituted with a heteroaryl group. Both “alkyl” and “heteroaryl” have been defined above. A heteroaralkyl is optionally substituted with one or more substituents such as alkyl (including carboxyalkyl, hydroxyalkyl, and haloalkyl such as trifluoromethyl), alkenyl, alkynyl, cycloalkyl, (cycloalkyl)alkyl, heterocycloalkyl, (heterocycloalkyl)alkyl, aryl, heteroaryl, alkoxy, cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, aralkyloxy, heteroaralkyloxy, aroyl, heteroaroyl, nitro, carboxy, alkoxycarbonyl, alkylcarbonyloxy, aminocarbonyl, alkylcarbonylamino, cycloalkylcarbonylamino, (cycloalkylalkyl)carbonylamino, arylcarbonylamino, aralkylcarbonylamino, (heterocycloalkyl)carbonylamino, (heterocycloalkylalkyl)carbonylamino, heteroarylcarbonylamino, heteroaralkylcarbonylamino, cyano, halo, hydroxy, acyl, mercapto, alkylsulfanyl, sulfoxy, urea, thiourea, sulfamoyl, sulfamide, oxo, or carbamoyl.
As used herein, “cyclic moiety” and “cyclic group” refer to mono-, bi-, and tri-cyclic ring systems including cycloaliphatic, heterocycloaliphatic, aryl, or heteroaryl, each of which has been previously defined.
As used herein, a “bridged bicyclic ring system” refers to a bicyclic heterocyclicalipahtic ring system or bicyclic cycloaliphatic ring system in which the rings are bridged. Examples of bridged bicyclic ring systems include, but are not limited to, adamantanyl, norbornanyl, bicyclo[3.2.1]octyl, bicyclo[2.2.2]octyl, bicyclo[3.3.1]nonyl, bicyclo[3.3.2]decyl, 2-oxabicyclo[2.2.2]octyl, 1-azabicyclo[2.2.2]octyl, 3-azabicyclo[3.2.1]octyl, and 2,6-dioxa-tricyclo[3.3.1.0 3a ]nonyl. A bridged bicyclic ring system can be optionally substituted with one or more substituents such as alkyl (including carboxyalkyl, hydroxyalkyl, and haloalkyl such as trifluoromethyl), alkenyl, alkynyl, cycloalkyl, (cycloalkyl)alkyl, heterocycloalkyl, (heterocycloalkyl)alkyl, aryl, heteroaryl, alkoxy, cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, aralkyloxy, heteroaralkyloxy, aroyl, heteroaroyl, nitro, carboxy, alkoxycarbonyl, alkylcarbonyloxy, aminocarbonyl, alkylcarbonylamino, cycloalkylcarbonylamino, (cycloalkylalkyl)carbonylamino, arylcarbonylamino, aralkylcarbonylamino, (heterocycloalkyl)carbonylamino, (heterocycloalkylalkyl)carbonylamino, heteroarylcarbonylamino, heteroaralkylcarbonylamino, cyano, halo, hydroxy, acyl, mercapto, alkylsulfanyl, sulfoxy, urea, thiourea, sulfamoyl, sulfamide, oxo, or carbamoyl.
As used herein, an “acyl” group refers to a formyl group or R X —C(O)— (such as alkyl-C(O)—, also referred to as “alkylcarbonyl”) where R X and “alkyl” have been defined previously. Acetyl and pivaloyl are examples of acyl groups.
As used herein, an “aroyl” or “heteroaroyl” refers to an aryl-C(O)— or a heteroaryl-C(O)—. The aryl and heteroaryl portion of the aroyl or heteroaroyl is optionally substituted as previously defined.
As used herein, an “alkoxy” group refers to an alkyl-O— group where “alkyl” has been defined previously.
As used herein, a “carbamoyl” group refers to a group having the structure —O—CO—NR X R Y or —NR X —CO—O—R Z , wherein R X and R Y have been defined above and R Z can be aliphatic, aryl, araliphatic, heterocycloaliphatic, heteroaryl, or heteroaraliphatic.
As used herein, a “carboxy” group refers to —COOH, —COOR X , —OC(O)H, —OC(O)R X , when used as a terminal group; or —OC(O)— or —C(O)O— when used as an internal group.
As used herein, a “haloaliphatic” group refers to an aliphatic group substituted with 1-3 halogen. For instance, the term haloalkyl includes the group —CF 3 .
As used herein, a “mercapto” group refers to —SH.
As used herein, a “sulfo” group refers to —SO 3 H or —SO 3 R X when used terminally or —S(O) 3 — when used internally.
As used herein, a “sulfamide” group refers to the structure —NR X —S(O) 2 —NR Y R Z when used terminally and —NR X —S(O) 2 —NR Y — when used internally, wherein R X , R Y , and R Z have been defined above.
As used herein, a “sulfamoyl” group refers to the structure —O—S(O) 2 —NR Y R Z wherein R Y and R Z have been defined above.
As used herein, a “sulfonamide” group refers to the structure —S(O) 2 —NR X R Y or —NR X —S(O) 2 —R Z when used terminally; or —S(O) 2 —NR X — or —NR X —S(O) 2 — when used internally, wherein R X , R Y , and R Z are defined above.
As used herein a “sulfanyl” group refers to —S—R X when used terminally and —S— when used internally, wherein R X has been defined above. Examples of sulfanyls include aliphatic-S—, cycloaliphatic-S—, aryl-S—, or the like.
As used herein a “sulfinyl” group refers to —S(O)—R X when used terminally and —S(O)— when used internally, wherein R X has been defined above. Exemplary sulfinyl groups include aliphatic-S(O)—, aryl-S(O)—, (cycloaliphatic(aliphatic))-S(O)—, cycloalkyl-S(O)—, heterocycloaliphatic-S(O)—, heteroaryl-S(O)—, or the like.
As used herein, a “sulfonyl” group refers to —S(O) 2 —R X when used terminally and —S(O) 2 — when used internally, wherein R X has been defined above. Exemplary sulfonyl groups include aliphatic-S(O) 2 —, aryl-S(O) 2 —, (cycloaliphatic(aliphatic))-S(O) 2 —, cycloaliphatic-S(O) 2 —, heterocycloaliphatic-S(O) 2 —, heteroaryl-S(O) 2 —, (cycloaliphatic(amido(aliphatic)))-S(O) 2 — or the like.
As used herein, a “sulfoxy” group refers to —O—SO—R X or —SO—O—R X , when used terminally and —O—S(O)— or —S(O)—O— when used internally, where R X has been defined above.
As used herein, a “halogen” or “halo” group refers to fluorine, chlorine, bromine or iodine.
As used herein, an “alkoxycarbonyl,” which is encompassed by the term carboxy, used alone or in connection with another group refers to a group such as alkyl-O—C(O)—.
As used herein, an “alkoxyalkyl” refers to an alkyl group such as alkyl-O-alkyl-, wherein alkyl has been defined above.
As used herein, a “carbonyl” refer to —C(O)—.
As used herein, an “oxo” refers to ═O.
As used herein, the term “phospho” refers to phosphinates and phosphonates. Examples of phosphinates and phosphonates include —P(O)(R P ) 2 , wherein R P is aliphatic, alkoxy, aryloxy, heteroaryloxy, (cycloaliphatic)oxy, (heterocycloaliphatic)oxy aryl, heteroaryl, cycloaliphatic or amino.
As used herein, an “aminoalkyl” refers to the structure (R X ) 2 N-alkyl-.
As used herein, a “cyanoalkyl” refers to the structure (NC)-alkyl-.
As used herein, a “urea” group refers to the structure —NR X —CO—NR Y R Z and a “thiourea” group refers to the structure —NR X —CS—NR Y R Z when used terminally and —NR X —CO—NR Y — or —NR X —CS—NR Y — when used internally, wherein R X , R Y , and R Z have been defined above.
As used herein, a “guanidine” group refers to the structure —N═C(N(R X R Y ))N(R X R Y ) or —NR X —C(═NR X )NR X R Y wherein R X and R Y have been defined above.
As used herein, the term “amidino” group refers to the structure —C═(NR X )N(R X R Y ) wherein R X and R Y have been defined above.
In general, the term “vicinal” refers to the placement of substituents on a group that includes two or more carbon atoms, wherein the substituents are attached to adjacent carbon atoms.
In general, the term “geminal” refers to the placement of substituents on a group that includes two or more carbon atoms, wherein the substituents are attached to the same carbon atom.
The terms “terminally” and “internally” refer to the location of a group within a substituent. A group is terminal when the group is present at the end of the substituent not further bonded to the rest of the chemical structure. Carboxyalkyl, i.e., R X O(O)C-alkyl is an example of a carboxy group used terminally. A group is internal when the group is present in the middle of a substituent of the chemical structure. Alkylcarboxy (e.g., alkyl-C(O)O— or alkyl-OC(O)—) and alkylcarboxyaryl (e.g., alkyl-C(O)O-aryl- or alkyl-O(CO)-aryl-) are examples of carboxy groups used internally.
As used herein, an “aliphatic chain” refers to a branched or straight aliphatic group (e.g., alkyl groups, alkenyl groups, or alkynyl groups). A straight aliphatic chain has the structure —[CH 2 ] v —, where v is 1-12. A branched aliphatic chain is a straight aliphatic chain that is substituted with one or more aliphatic groups. A branched aliphatic chain has the structure —[CQQ] v — where Q is independently a hydrogen or an aliphatic group; however, Q shall be an aliphatic group in at least one instance. The term aliphatic chain includes alkyl chains, alkenyl chains, and alkynyl chains, where alkyl, alkenyl, and alkynyl are defined above.
The phrase “optionally substituted” is used interchangeably with the phrase “substituted or unsubstituted.” As described herein, compounds of the invention can optionally be substituted with one or more substituents, such as are illustrated generally above, or as exemplified by particular classes, subclasses, and species of the invention. As described herein, the variables R 1 , R 2 , R 3 , and other variables contained in Formulae described herein encompass specific groups, such as alkyl and aryl. Unless otherwise noted, each of the specific groups for the variables R 1 , R 2 , R 3 , and other variables contained therein can be optionally substituted with one or more substituents described herein. Each substituent of a specific group is further optionally substituted with one to three of halo, cyano, oxo, alkoxy, hydroxy, amino, nitro, aryl, cycloaliphatic, heterocycloaliphatic, heteroaryl, haloalkyl, and alkyl. For instance, an alkyl group can be substituted with alkylsulfanyl and the alkylsulfanyl can be optionally substituted with one to three of halo, cyano, oxo, alkoxy, hydroxy, amino, nitro, aryl, haloalkyl, and alkyl. As an additional example, the cycloalkyl portion of a (cycloalkyl)carbonylamino can be optionally substituted with one to three of halo, cyano, alkoxy, hydroxy, nitro, haloalkyl, and alkyl. When two alkoxy groups are bound to the same atom or adjacent atoms, the two alkxoy groups can form a ring together with the atom(s) to which they are bound.
In general, the term “substituted,” whether preceded by the term “optionally” or not, refers to the replacement of hydrogen radicals in a given structure with the radical of a specified substituent. Specific substituents are described above in the definitions and below in the description of compounds and examples thereof. Unless otherwise indicated, an optionally substituted group can have a substituent at each substitutable position of the group, and when more than one position in any given structure can be substituted with more than one substituent selected from a specified group, the substituent can be either the same or different at every position. A ring substituent, such as a heterocycloalkyl, can be bound to another ring, such as a cycloalkyl, to form a spiro-bicyclic ring system, e.g., both rings share one common atom. As one of ordinary skill in the art will recognize, combinations of substituents envisioned by this invention are those combinations that result in the formation of stable or chemically feasible compounds.
The phrase “stable or chemically feasible,” as used herein, refers to compounds that are not substantially altered when subjected to conditions to allow for their production, detection, and preferably their recovery, purification, and use for one or more of the purposes disclosed herein. In some embodiments, a stable compound or chemically feasible compound is one that is not substantially altered when kept at a temperature of 40° C. or less, in the absence of moisture or other chemically reactive conditions, for at least a week.
As used herein, an “effective amount” is defined as the amount required to confer a therapeutic effect on the treated patient, and is typically determined based on age, surface area, weight, and condition of the patient. The interrelationship of dosages for animals and humans (based on milligrams per meter squared of body surface) is described by Freireich et al., Cancer Chemother. Rep., 50: 219 (1966). Body surface area may be approximately determined from height and weight of the patient. See, e.g., Scientific Tables, Geigy Pharmaceuticals, Ardsley, N.Y., 537 (1970). As used herein, “patient” refers to a mammal, including a human.
Unless otherwise stated, structures depicted herein are also meant to include all isomeric (e.g., enantiomeric, diastereomeric, and geometric (or conformational)) forms of the structure; for example, the R and S configurations for each asymmetric center, (Z) and (E) double bond isomers, and (Z) and (E) conformational isomers. Therefore, single stereochemical isomers as well as enantiomeric, diastereomeric, and geometric (or conformational) mixtures of the present compounds are within the scope of the invention. Unless otherwise stated, all tautomeric forms of the compounds of the invention are within the scope of the invention. Additionally, unless otherwise stated, structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of hydrogen by deuterium or tritium, or the replacement of a carbon by a 13 C— or 14 C-enriched carbon are within the scope of this invention. Such compounds are useful, for example, as analytical tools or probes in biological assays, or as therapeutic agents.
Chemical structures and nomenclature are derived from ChemDraw, version 11.0.1, Cambridge, Mass.
II. COMMONLY USED ABBREVIATIONS
The following abbreviations are used:
PG protecting group LG leaving group DCM dichloromethane Ac acetyl DMF dimethylformamide EtOAc ethyl acetate DMSO dimethyl sulfoxide MeCN acetonitrile TCA trichloroacetic acid ATP adenosine triphosphate EtOH ethanol Ph phenyl Me methyl Et ethyl Bu butyl DEAD diethylazodicarboxylate HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid BSA bovine serum albumin DTT dithiothreitol MOPS 4-morpholinepropanesulfonic acid NMR nuclear magnetic resonance HPLC high performance liquid chromatography LCMS liquid chromatography-mass spectrometry TLC thin layer chromatography Rt retention time HOBt hydroxybenzotriazole Ms mesyl Ts tosyl Tf triflyl Bs besyl Ns nosyl Cbz carboxybenzyl Moz p-methoxybenzyl carbonyl Boc tert-butyloxycarbonyl Fmoc 9-fluorenylmethyloxycarbonyl Bz benzoyl Bn benzyl PMB p-methoxybenzyl DMPM 3,4-dimethoxybenzyl PMP p-methoxyphenyl
III. METHODS OF SYNTHESIZING COMPOUNDS OF FORMULA I
One aspect of the present invention provides a novel synthesis for generating thiazolidine compounds that are useful for the treatment of metabolic disorders. This synthetic method is useful for preparing a compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein each of R 1 and R 2 is independently selected from H, halo, aliphatic, and alkoxy, wherein the aliphatic or alkoxy is optionally substituted with 1-3 of halo; comprising the step of:
converting a compound of Formula 2A into a compound of Formula I
wherein R 3 is hydrogen or an optionally substituted C 1-6 alkyl. In some embodiments, the compound of Formula 2A undergoes hydrolysis to generate a compound of Formula I. For example, the compound of Formula 2A is treated with an acid to generate the compound of Formula I. In other examples, the compound of Formula 2A is treated with an acid and heat to generate a compound of Formula I.
In some embodiments, R 3 is methyl, ethyl, propyl, isopropyl, butyl, or tert-butyl, each of which is optionally substituted. In other embodiments, R 3 is methyl, ethyl, propyl, isopropyl, butyl, or tert-butyl, each of which is unsubstituted. And, in some embodiments, R 3 is hydrogen.
Some embodiments further comprise reacting a compound of Formula 3A with a compound of Formula 4A:
wherein X 1 is a leaving group (e.g., halo or triflyl), to generate the compound of Formula 2A.
In some embodiments, the compound of Formula 4A comprises
In some embodiments, the compound of Formula 4A comprises
In some embodiments, the compound of Formula 4A comprises
In some embodiments, the compound of Formula 4A comprises
Some embodiments further comprise converting a compound of Formula 5A
wherein X 1 is a leaving group, to a compound of Formula 4A.
In some embodiments, X 1 is a halo (e.g., Cl or Br) or triflyl group. In some embodiments, the compound of Formula 5A is treated with a reagent R 3 ONH 2 .Cl, wherein R 3 is defined above. In some examples, the reagent comprises HONH 2 .HCl, TMSNHOTMS, (H 2 NOH) 2 .H 2 SO 4 , CH 3 ONH 2 .HCl, or any combination thereof to generate a compound of Formula 4A.
In some embodiments, the compound of Formula 5A comprises
wherein X 1 is Cl or Br.
Some embodiments further comprise converting a compound of Formula 6A
to a compound of Formula 5A. For example, the compound of Formula 6A undergoes halogenation to generate a compound of Formula 5A.
In some embodiments, the compound of Formula 6A comprises
wherein R 1 is selected from a C 1-6 alkyl or C 1-6 alkoxy, either of which is optionally substituted with 1-3 halo, and R 2 is —H or halo.
In some embodiments, R 1 is a C 1-6 alkyl optionally substituted with 1-3 halo. For example, R 1 is selected from methyl, ethyl, or propyl, any of which is optionally substituted with 1-3 halo.
In other embodiments, the compound of Formula 6A comprises
Some embodiments further comprise reacting the compound
with the compound
under condensation conditions to form a compound of Formula 3B
Other embodiments further comprise reducing the compound of Formula 3B to generate a compound of Formula 3A
Another aspect of the present invention provides a novel synthesis for generating a compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein each of R 1 and R 2 is independently selected from H, halo, aliphatic, and alkoxy, wherein the aliphatic or alkoxy is optionally substituted with 1-3 of halo; comprising the step of:
converting a compound of Formula 2A into a compound of Formula I
wherein R 3 is hydrogen or an optionally substituted C 1-6 alkyl. In some embodiments, the compound of Formula 2A undergoes hydrolysis to generate a compound of Formula I. For example, the compound of Formula 2A is treated with an acid to generate the compound of Formula I. In other examples, the compound of Formula 2A is treated with an acid and heat to generate a compound of Formula I.
In some embodiments, R 3 is methyl, ethyl, propyl, isopropyl, butyl, or tert-butyl, each of which is optionally substituted. In other embodiments, R 3 is methyl, ethyl, propyl, isopropyl, butyl, or tert-butyl, each of which is unsubstituted. And, in some embodiments, R 3 is hydrogen.
Some embodiments further comprise converting a compound of Formula 7A into a compound of Formula 2A:
In some embodiments, the compound of Formula 7A is converted to a compound of Formula 2A under reduction conditions. For example, the compound of Formula 2A is generated by treating the compound of Formula 7A with a reducing reagent comprising NaBH 4 (e.g., NaBH 4 and CoCl 2 ).
In some embodiments, the compound of Formula 7A comprises
Some embodiments further comprise reacting a compound of Formula 8A
with the compound
to generate a compound of Formula 7A.
In some embodiments, the compound of Formula 8A is reacted with the compound
under condensation conditions. For example, the compound of Formula 8A is reacted with the compound
in the presence of an acid (e.g., benzoic acid) and heat.
In some embodiments, the compound of Formula 8A comprises
Some embodiments further comprise reacting a compound of Formula 4A, as defined above, with the compound
to generate a compound of Formula 8A.
Some embodiments further comprise converting a compound of Formula 5A
wherein X 1 is a leaving group, to a compound of Formula 4A.
In some embodiments, X 1 is a halo (e.g., Cl or Br) or triflyl group. In some embodiments, the compound of Formula 5A is treated with a reagent of the general formula R 3 ONH 2 .HCl or (R 3 ONH 2 ) 2 .H 2 SO 4 , wherein R 3 is defined above. In some instances, R 3 ONH 2 comprises HONH 2 , TMSNHOTMS, CH 3 ONH 2 , CH 3 CH 2 ONH 2 , or any combination thereof to generate a compound of Formula 4A.
In some embodiments, the compound of Formula 5A comprises
wherein X 1 is Cl or Br.
Some embodiments further comprise converting a compound of Formula 6A
to a compound of Formula 5A. For example, the compound of Formula 6A undergoes halogenation to generate a compound of Formula 5A.
In some embodiments, the compound of Formula 6A comprises
wherein R 1 is selected from a C 1-6 alkyl or C 1-6 alkoxy, either of which is optionally substituted with 1-3 halo, and R 2 is —H or halo.
In some embodiments, R 1 is a C 1-6 alkyl optionally substituted with 1-3 halo. For example, R 1 is selected from methyl, ethyl, or propyl, any of which is optionally substituted with 1-3 halo.
In other embodiments, the compound of Formula 6A comprises
IV. EXEMPLARY SYNTHESES
The following synthetic schemes illustrate some examples of methods for generating compounds of Formula I according to the present invention.
wherein R 1 , R 2 , R 3 , and X 1 are defined above.
A compound of Formula I can be synthesized according to Scheme 1, wherein a thiazolidine-2,4-dione of Formula 3A is alkylated by an alkoxylimine of Formula 4A to form a compound of Formula 2A, wherein X 1 is a leaving group such as halo, tosyl, mesyl, or trifluoromethane sulfonyl. The alkylation can be accomplished under basic conditions. Exemplary solvents are polor aprotic solvents such as DMSO or DMF, and the base can be a strong base, such as potassium tert-butoxide. The intermediate 2A is treated with an acid (e.g., 6M HCl in acetic acid) to generate a compound of Formula I. This transformation can also be performed under elevated temperatures.
In some embodiments, the compound of Formula 3A is generated according to Scheme 1A:
A compounds of Formula 3A can be synthesized according to Scheme 1A, wherein 4-hydroxybenzaldehyde is condensed with thiazolidine-2,4-dione under Knoevenagel conditions to produce (E)-5-(4-hydroxybenzylidene)thiazolidine-2,4-dione. This intermediate can then be reduced to the compound of Formula 3A by, for example, hydrogenation.
In several embodiments, the compound of Formula 4A is formed according to Scheme 1B:
The synthesis of intermediate 4A can be accomplished first by acetylation of a 2-pyridyl lithium species produced from contacting a 2-bromopyridine species with n-butyllithium, with an appropriate acetamide compound. The resulting acetyl compound, having another bromine substituent, can then be coupled with an unsubstituted C 1-3 alkyl substituent using a palladium catalyst to generate the intermediate compound 6A. Halogenation of the alpha position of intermediate 6A using a molecular halogen compound provides the halogenated intermediate compound 5A. Compound of Formula 4A can then be produced by exposure of 5A with the appropriate alkoxylamine compound under acidic alcoholic conditions. An example of the production of a compound of Formula 4A from a compound of Formula 5A is provided in Scheme 1C. As shown in the scheme, treatment of a compound of Formula 5A, wherein X is Br, with O-alkoxylamine hydrochloride in ethanol provides a compound of Formula 4A.
In other embodiments, the compound of Formula I is generated according to Scheme 2.
wherein R 1 , R 2 , R 3 , and X 1 are defined above.
4-hydroxybenzaldehyde is first alkylated by an alkoxylimine of Formula 4A to provide intermediate 8A. Enol condensation of a compound of Formula 4A with thiazolidine-2,4-dione under acidic conditions using pyrrolidine as the solvent provides a compound of Formula 7A. Further reduction of the olefin using cobalt chloride and sodium borohydride provides a compound of Formula 2A, which can be converted to the ketone using an acid such as glyoxylic acid or pyruvic acid at elevated temperatures.
V. NOVEL COMPOUNDS
Another aspect of the present invention provides a compound of Formula 10A, 10B, or 10C
wherein R 1 is halo, C 1-6 alkyl optionally substituted with 1-3 halo, or C 1-6 alkoxy optionally substituted with 1-3 halo; R 3 is hydrogen or unsubstituted C 1-6 alkyl; and X A is a leaving group or hydrogen.
In several embodiments, R 3 of Formula 10A, 10B, or 10C is hydrogen. In other embodiments, R 3 of Formula 10A, 10B, or 10C is methyl, ethyl, propyl, isopropyl, butyl, or tert-butyl, each of which is unsubstituted.
Another aspect of the present invention provides a compound of Formula 10D, 10E, or 10F
wherein R 1 and X A are defined above.
Another aspect of the present invention provides a compound Formula 11A-11M
wherein X A and R 3 are defined above.
In some embodiments, X A is a leaving group selected from —Br, —Cl, —I, —OMs, —OTs, —OTf, —OBs, —ONs, —O-tresylate, or —OPO(OR 4 ) 2 , wherein each R 4 is independently C 1-4 alkyl or two of R 4 together with the oxygen and phosphorous atoms to which they are attached form a 5-7 membered ring. In other embodiments, X A is hydrogen.
Another aspect of the present invention provides a compound of Formula 2A
wherein each of R 1 , R 2 , and R 3 is defined above. For example, in one embodiment, the compound of Formula 2A comprises
And, another aspect of the present invention provides a compound selected from
wherein R 3 is defined above.
VI. EXAMPLES
Example 1
Preparation of 1-(5-bromopyridin-2-yl)ethanone
In a 3-neck 1000 ml round bottom flask, 2,5-dibromopyridine (10.0 g, 42.2 mmol) was dissolved in toluene (400 ml) and cooled to −40° C. (CH 3 CN/dry ice). 1.6 M of n-butyllithium in tetrahydrofuran (26.38 mL, 42.21 mmol) was slowly added to the cooled solution to form a deep reddish solution, which was stirred at −40° C. for 40 minutes. N,N-Dimethylacetamide (7.14 mL, 76.8 mmol) was added with no discernable change. The mixture was allowed to slowly warm to room temperature. Then, the mixture was quenched by adding 25 ml sat'd ammonium chloride. Added 100 ml H 2 O and extracted with EtOAc (250 ml). The organic phase was washed with water (200 ml). The combined aqueous phases were extracted with EtOAc (100 ml). The combined organic extracts were washed with brine, dried (Na 2 SO 4 ), filtered and evaporated in vacuo to generate 6.31 g of a tan solid. 1 H-NMR (CDCl 3 ): δ 8.74 (d, J=1.9 Hz, 1H), 7.96 (m, 2H), 2.70 (s, 3H). HPLC: RT=3.237 min., 60 area % @ 210 nm; RT=3.238 min., 87 area % @254 nm. LCMS: MS (ESI—) for C 8 H 7 BrO m/z 201.0 (M+H) + .
Example 2
Preparation of (1-(5-ethylpyridin-2-yl)ethanone
A mixture of 1-(5-bromopyridin-2-yl)ethanone (6.30 g, 31.5 mmol; Supplier=Kalexsyn; Lot=90) and [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (560 mg, 0.76 mmol) in dioxane (120 ml) was degassed by sparging with N 2 for 10 minutes. Added a solution (15% w/w) of diethyl zinc in hexane (50 ml) slowly, dropwise and heated to 50° C. The orange mixture turned dark, ultimately generating a dark orange with yellow solids as it stirred at 50° C. for 30 minutes. Allowed to cool to room temperature. The reaction mixture was partitioned between EtOAc (200 ml) and water (200 ml), and the aqueous phase was extracted 2× with EtOAc. The combined organic phases were washed with brine (500 ml), dried (Na 2 SO 4 ), filtered and evaporated in vacuo to give 4.14 g brown oil. Distilled under high vac using short-path distillation apparatus. BP=55° C. @ 0.32 torr to give 2.249 g of slightly tinted oil. 1 H-NMR (CDCl 3 ): δ 8.50 (d, J=1.9 Hz, 1H), 7.96 (d, J=7.9 Hz, 1H), 7.63 (dd, J=8.0, 2.2 Hz, 1H), 2.71 (m, 2H), 2.69 (s, 3H), 1.27 (t, J=7.6 Hz, 3H). HPLC: 2.011 min., 57 area % @ 210 nm; 2.012 min., 75 area % @ 254 nm. LCMS: MS (ESI—) for C 10 H 12 O m/z 150.1 (M+H) + .
Example 3
Preparation of 22-bromo-1-(5-ethylpyridin-2-yl)ethanone hydrogen bromide
To a stirring solution of 1-(5-ethylpyridin-2-yl)ethanone (634 mg, 4.25 mmol; Supplier=Kalexsyn; Lot=1003-TTP-112) in 33% HBr/HOAc (w/w, 5 ml) at 10° C. (water bath with a little ice) was added 0.173 ml bromine dropwise. Stirred for 1 hour at room temperature at which time the reaction appeared complete by HPLC. Added ether (5 ml) and stirred for 15 minutes. The orange solids were collected by suction filtration, washed with ether, and dried under high vac. 1.042 g orange solid. 1 H-NMR (DMSO-d6): δ 9.65 (brs, 1H), 8.62 (d, J=1.9 Hz, 1H), 7.97 (m, 1H), 7.91 (d, J=2.1 Hz, 1H), 4.99 (s, 2H), 2.74 (q, J=7.5 Hz, 2H), 1.22 (t, J=7.6 Hz, 3H). HPLC: 3.747 min., 83 area % @ 2540 nm; 3.747 min., 95 area % @ 210 nm. MS (ESI—) for C 9 H 10 BrNO m/z 229.1 (M+H) + .
Example 4
Preparation of 2-bromo-1-(5-ethylpyridin-2-yl)ethanone O-methyl oxime
To a stirring solution of 2-bromo-1-(5-ethylpyridin-2-yl)ethanone hydrobromide (1.024 g, 3.314 mmol; Supplier=Kalexsyn; Lot=1003-TTP-185) in EtOH (10 ml) was added methoxylamine hydrochloride (553.5 mg, 6.628 mmol). Left to stir at RT overnight. The reaction mixture was evaporated in vacuo. The residue was dissolved in DCM and an equal volume of saturated NaHCO 3 was added and the biphasic mixture stirred for 30 minutes. The phases were separated and the aqueous phase was extracted with DCM. The combined organic phases were dried (Na 2 SO 4 ), filtered and evaporated in vacuo to afford a pale yellow oil which crystallized upon standing. 1 H-NMR (CDCl 3 ): δ 8.50 (s, 1H), 7.87 (d, J=8.3 Hz, 1H), 7.59 (m, 1H), 4.79 (s, 1H), 4.64 (s, 1H), 4.13 (d, J=4.4 Hz, 3H), 2.70 (q, J=7.7 Hz, 2H), 1.28 (t, J=7.7 Hz, 3H). HPLC: 3.429 min., 30 area % and 3.621 min., 31 area % @ 210 nm; 3.414 min., 36 area % and 3.618 min., 36 area % @ 210 nm. MS (ESI—) for C 10 H 13 BrN 2 O m/z 258.2 (M+H) + .
Example 5
Preparation of 5-(4-(2-(5-ethylpyridin-2-yl)-2-(methoxyimino)ethoxy)benzyl)thiazolidine-2,4-dione
To a stirring solution of 5-(4-hydroxybenzyl)thiazolidine-2,4-dione (210 mg, 0.941 mmol) in DMSO was added potassium tert-Butoxide (227 mg, 2.02 mmol) in a single portion. Stirred at RT for 15 minutes. Added a solution of (1Z)-2-bromo-1-(5-ethylpyridin-2-yl)ethanone O-methyloxime (242 mg, 0.941 mmol; Supplier=Kalexsyn; Lot=1003-TTP-186) in DMSO (2 ml). Added 1M HCl until pH of mixture was about 3. Extracted with EtOAc. The extract was washed with water, dried (Na 2 SO 4 ), filtered and evaporated in vacuo to give an off-white foam. 278 mg. 1 H-NMR (DMSO-d6): δ12.05 (brs, 1H), 8.47 (d, J=1.7 Hz, 1H), 7.77 (m, 1H), 7.70 m, 1H), 7.14 (d, J=8.5 Hz, 2H), 6.90 (d, J=8.5 Hz, 2H), 5.17 (s, 2H), 4.87 (dd, J=8.9, 4.4 Hz, 1H), 4.01 (s, 3H), 3.30 (dd, J=14.2, 4.5 Hz, 1H), 3.06 (dd, J=14.1, 9.1 Hz, 1H), 2.64 (q, J=7.7 Hz, 2H), 1.19 (t, J=7.6 Hz, 3H). HPLC: 3.103 min., 82 area % and 3.379 min., 18 area % @254 nm; 3.109 min., 91 area % and 3.379 min., 9 area % @ 254 nm. MS (ESI—) for C 20 H 21 N 3 O 4 S m/z 400.3 (M+H) + : m/z 398.3 (M−H) −
Example 6
Preparation of 5-(4-(2-(5-ethylpyridin-2-yl)-2-oxoethoxy)benzyl)thiazolidine-2,4-dione
A stirring solution of 5-(4-{[(2Z)-2-(5-ethylpyridin-2-yl)-2-(methoxyimino)ethyl]oxy}benzyl)-1,3-thiazolidine-2,4-dione (81 mg, 0.20 mmol; Supplier=Kalexsyn; Lot=1003-TTP-194) in 6M HCl (2 ml) and pyruvic acid (0.5 ml) was heated at 75° C. After 2 h at 75° C. HPLC showed reaction was complete. Neutralized with sat'd NaHCO 3 and extracted with EtOAc. Extract dried (Na 2 SO 4 ), filtered and evaporated in vacuo to give 45 mg (60%) pale yellow oil. 1 H-NMR (DMSO-d6): δ12.02 (brs, 1H), 8.64 (s, 1H), 7.91 (m, 1H), 7.14 (d, J=8.5 Hz, 2H), 6.88 (d, J=8.5 Hz, 2H), 5.66 (s, 2H), 4.87 (dd, J=9.2, 4.3 Hz, 1H), 3.31 (m, 1H), 3.05 (dd, J=14.1, 9.1 Hz, 1H), 2.74 (q, J=7.7 Hz, 2H), 1.23 (t, J=7.7 Hz, 3H). HPLC (3.860 min., 100 area % @ 210 and 254 nm. MS (ESI—) for C 19 H 18 N 2 O 4 S m/z 371.3 (M+H) + : m/z 369.4 (M−H) −
Example 7
Assays
Assays for Measuring Reduced PPARγ Receptor Activation
Whereas activation of the PPARγ receptor is generally believed to be a selection criteria to select for molecules that may have anti-diabetic and insulin sensitizing pharmacology, this invention finds that activation of this receptor should be a negative selection criterion. Molecules will be chosen from this chemical space because they have reduced, not just selective, activation of PPARγ. The optimal compounds have at least a 10-fold reduced potency as compared to pioglitazone and less than 50% of the full activation produced by rosiglitazone in assays conducted in vitro for transactivation of the PPARγ receptor. The assays are conducted by first evaluation of the direct interactions of the molecules with the ligand binding domain of PPARγ. This can be performed with a commercial interaction kit that measures the direct interaction by florescence using rosiglitazone as a positive control. Further assays can be conducted in a manner similar to that described by Lehmann et al. [Lehmann J M, Moore L B, Smith-Oliver T A: An Antidiabetic Thiazolidinedione is a High Affinity Ligand for Peroxisome Proliferator-activated Receptor (PPAR) J. Biol. Chem. (1995) 270: 12953] but will use luciferase as a reporter as in Vosper et al. [Vosper, H., Khoudoli, G A, Palmer, C N (2003) The peroxisome proliferators activated receptor d is required for the differentiation of THP-1 moncytic cells by phorbol ester. Nuclear Receptor 1:9]. Compound stocks will be dissolved in DMSO and added to the cell cultures at final concentrations of 0.1 to 100 μM and the relative activation will be calculated as induction of the reporter gene (luciferase) as corrected for by the expression of the control plasmid (coding for galactosidase). Pioglitazone and rosiglitazone will be used as reference compounds as described above.
In addition to showing the reduced activation of the PPARγ receptor in vitro, the compounds will not produce significant activation of the receptor in animals. Compounds dosed to full effect for insulin sensitizing actions in vivo (see below) will be not increase activation of PPARγ in the liver as measured by the expression of a P2, a biomarker for ectopic adipogenesis in the liver [Matsusue K, Haluzik M, Lambert G, Yim S-H, Oksana Gavrilova O, Ward J M, Brewer B, Reitman M L, Gonzalez F J. (2003) Liver-specific disruption of PPAR in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes. J. Clin. Invest.; 111: 737] in contrast to pioglitazone and rosiglitazone, which do increase a P2 expression under these conditions.
The insulin sensitizing and antidiabetic pharmacology are measured in the KKA Y mice as previously reported [Hofmann, C., Lornez, K., and Colca, J. R. (1991). Glucose transport deficiency corrected by treatment with the oral anti-hyperglycemic agent Pioglitazone. Endocrinology, 129:1915-1925]. Compounds are formulated in 1% sodium carboxy methylcellulose, and 0.01% tween 20 and dosed daily by oral gavage. After 4 days of once daily treatment, treatment blood samples are taken from the retro-orbital sinus and analyzed for glucose, triglycerides, and insulin as described in Hofmann et al. Doses of compounds that produce at least 80% of the maximum lowering of glucose, triglycerides, and insulin will not significantly increase the expression of a P2 in the liver of these mice.
Other Embodiments
It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims. | The present invention provides novel methods for synthesizing PPARγ sparing compounds, e.g., thiazolidinediones, that are useful for preventing and/or treating metabolic disorders such as diabetes, obesity, hypertension, and inflammatory diseases. | 2 |
FIELD OF THE INVENTION
This invention relates to shoe soles, and particularly to a novel shoe sole construction comprised of a leather-blank or blocker having an insert of thermoplastic material secured in a cut-out area in the forward portion of the leather blank to provide improved traction and wear.
BACKGROUND OF THE INVENTION
Various attempts have been made to provide a shoe sole construction that combines the look of leather with the durability and traction of rubber or other synthetic material. For example, in one such construction, a thermally moldable material is injected onto the entire top surface (i.e., shoe-side) of the leather sole, with a portion of the material extending into and through a cut-out region in the sole. However, this construction presents several disadvantages. First, the thermal material is visible at the sole edges between the midsole and the leather sole itself. Second, if the thermoplastic material is not evenly distributed, the heel of the shoe will not sit properly. Third, the construction is simply too heavy and too rigid, and delamination too often occurs at the shoe edges. Another construction utilizes a synthetic portion attached only on the street-side of the sole, but sole failure or separation has been a recurring problem in such a construction. Still another construction includes a thermoplastic insert molded into a cut-out region in the sole, but this construction has been unsatisfactory because the thermoplastic material has tended to shrink and to pull away from the edge of the cut-out region on the street-side of the sole, resulting in sole failure or separation.
It is therefore an object of the present invention to provide a sole construction comprised of leather and synthetic material in which the sole is lightweight and relatively flexible.
It is another object of this invention to provide such a sole construction having an aesthetically pleasing appearance with no thermal material visible at the edge of the sole.
It is a still further object of this invention to provide a sole construction in which the synthetic material is firmly secured to the leather so as to prevent its separation from the leather, particularly at the edge of the thermal insert, and in which the material does not shrink away from the sole.
SUMMARY OF THE INVENTION
The foregoing objects are achieved and the foregoing problems solved by one illustrative embodiment of the present invention in which a thermally-moldable material is secured in a cut-out region of a leather blank, the edge of the cut-out region being bevelled and the thermally-moldable material being shaped so as to cooperate with said bevelled edge to provide a mechanical "lock" between the leather and the material.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a typical shoe that includes the novel sole construction of the instant invention.
FIG. 2 is a plan view of a leather sole blank (shoe side) having a cut-out area in which a thermoplastic insert will be injected in accordance with the instant invention.
FIG. 3 is an enlarged cross-sectional view of the blank of FIG. 2, as seen along the line A--A, showing the edges of the cut-out area.
FIG. 4 is an enlarged cross-sectional view of the sole construction of the instant invention, after the thermoplastic insert has been injection molded into blank 22.
FIG. 5 is a cross-sectional view, along the line B--B of FIG. 2, of the portion of the mold that forms a lip in the thermoplastic insert on the street side of the blank.
FIG. 6 is a cross-sectional view of the portion of the mold that forms a tapered edge in the insert on the shoe side of the blank.
FIG. 7 is a plan view of the street-side of the sole construction of the preferred embodiment of the present invention.
FIG. 8 is a plan view of the upper (shoe) side of the sole of FIG. 7.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
FIG. 1 depicts a standard loafer 10 that includes the novel sole construction of the instant invention. Sole 20 is seen to include leather portion 22 and insert 30 of thermoplastic material. The specific construction of sole 20 will be described in conjunction with the remaining drawings.
Turning to FIG. 2, there is depicted a blank of leather 22 from which a portion has been removed, leaving cut-out area 24, defined by circumferential edge 26. As seen in FIGS. 2 through 6, edge 26 is bevelled on the shoe side of blank 22 around the perimeter of cut-out area 24. The cut-out area 24 and insert 30 extend over a major portion of the forward region of the sole 20 so that the insert 30 has lateral dimensions in the plane of sole 30 much greater than the thickness of insert 30. In particular, edge 26 is bevelled at 28 at an angle of at most 4 degrees from the plane of sole 20, the taper extending about one-half inch toward the outer edge of the sole. This bevel 28 is introduced by means of a reducing matrix, the amount of material to be removed depending on the thickness of the particular leather blank to be placed in the mold. Bevel 28 assists in providing proper flow of the thermoplastic material in order to form tapered edge 34.
After edge 26 is bevelled, urethane cement (for example, Upaco #3249) is applied on the bevelled (reduced) area 28 around the perimeter of cut-out area 24 on the shoe side of blank 22. When the cement has dried, blank 22 is placed in an injection mold, and the thermoplastic material is injected into the cut-out area as more fully described below.
FIG. 4 is an enlarged cross-sectional view of the sole construction of this invention in the area where insert 30 meets blank 22. Insert 30 preferably includes a lip 32 extending outwardly on the street side of blank 22, and a tapered edge 34 on the shoe side of blank 22, both lip 32 and tapered edge 34 extending around the entire periphery of the cut-out area 24. Lip 32 extends approximately 0.040 inches from the edge of cut-out area 24 toward the outer edge of blank 22, and is approximately 0.030 inch in height at its highest point. To ensure proper and complete molding of lip 32, the outer corner of lip 32 is tapered at 33 at an angle of approximately 5°. In FIG. 5 is depicted the portion of the mold that forms lip 32. Tapered edge 34 on the shoe side of blank 22 is formed so as to mate with bevelled area 28 (FIG. 3). As seen in FIG. 6, which depicts the portion of the mold that forms tapered edge 34, a 4° taper is provided by the mold, which, combined with the bevelled (reduced) area 28 of the leather blank, produces a tapered edge 34 of no more than 8°, depending on the amount of material removed from blank 22 at area 28 during the reducing step described above.
Lip 32 and tapered edge 34 cooperate with edge 26 to secure the injected insert 30 in place in cut-out area 24. Insert 30 is effectively prevented from detachment from blank 22 in the direction toward the street side of the sole by means of tapered edge 34, which is sandwiched between blank 22 and the midsole of the shoe. It is prevented from detachment or movement in a direction toward the shoe side of sole 20 by means of lip 32, which effectively provides a mechanical lock between the insert and edge 26 of blank 22. It should be noted that, during the molding process, corner 35 of edge 26 (see FIG. 4) may become somewhat compressed or rounded off due to the pressure of the molded material, but this circumstance has been found not to affect the utility or performance of the subject invention.
As previously indicated, tapered edge 34 preferably extends outwardly about one-half inch from edge 26 of cut-out area 24. Lip 32 extends outwardly about 0.0040 inch beyond edge 26 at the street side of sole 20. In a typical construction such as here depicted, leather blank 22 is approximately one iron (one-eighth inch) thick. Insert 30 is about 0.150 inch thick at its thickest point.
Because of the bevelled area 28 of blank 22 and the mating tapered edge 34 of insert 30, insert 30 presents a very low profile on the shoe side of sole 20. Consequently, sole 22 can mate with the midsole of the shoe without producing a bulge, since the bulk of the moldable material forming insert 30 occupies cut-out area 24. Moreover, the thermoplastic material will not be visible at the edge of the shoe, and delamination at the edge of the shoe will be minimized because this invention permits a leather-to-leather bond at the shoe edge.
FIGS. 7 and 8, respectively, depict the shoe-side and the street-side of the sole construction of the instant invention. In the preferred embodiment here depicted, the thermal insert 30 includes conventional tread 36 to provide improved traction.
In the structure here described, a special blend of polyvinyl chloride-urethane available from Gary Chemicals of Leominster, Mass., no. GTX85-091, was found to be best suited for insert 30. This compound will flow easily at 280° F. to 305° F., so that the leather blank will not be burned during the molding process. Use of a low pressure, slow injection molding machine such as United Shoe Machinery model F was found to produce satisfactory results.
It will be readily appreciated by those skilled in the art that the present invention in its broader aspects is not limited to the specific embodiments herein shown and described. Accordingly, variations may be made from the embodiments described herein which are within the scope of the accompanying claims, without departing from the principles of the invention and without sacrificing its chief advantages. | The shoe of the invention consists of a thermally-moldable material which is secured in a cut-out region of the shoe sole. | 0 |
RELATED APPLICATIONS
This application claims priority to U.S. Patent Application No. 60/439,624 filed Jan. 13, 2003, the disclosure of which is incorporated herein by reference in its entirety.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to methods and devices for the transportation of droplets or particles using an electric field gradient.
2. Background
The scaling down of chemical reactions, separations, and analysis processing using microfluidic devices may be useful in various areas of chemical engineering, pharmaceuticals, and biotechnology. Many of the microfluidic devices operate by microchannels inside plastic or glass, which can lead to surface fouling and other problems. The fluids of interest may be in direct contact with the plastic or glass. The liquid inside these channels generally flows in a continuous stream because high capillary pressures generated at any air-liquid boundaries in the microchannels may disrupt operation. Pumping and valving in such small channels may require a significant amount of energy because of high viscous dissipation. Therefore, many of these devices operate as continuous process devices.
Alternatives to continuous streams in microchannels include methods to move a liquid as a micro- or nano-droplet(s) using electric fields or gradients in interfacial tensions. The manipulation of microscopic droplets on a solid surface, however, may be technically difficult. For example, the contact angle hysteresis of the droplets can lead to strong capillary forces, which may increase losses of power and may pin the droplets onto surface contaminants and/or scratches. The open surface of the droplets, combined with the high capillary pressure in the droplets, may lead to rapid evaporation and/or surface fowling. In addition, molecular, particulate, or biological species inside the droplets can become adsorbed on the surface of the solid, which can lead to a loss of the component for which processing is desired, higher contact angle hysteresis and chip contamination that can be difficult to reverse.
The manipulation of microdroplets can also be based on the application of alternating current (“AC”) electric fields, called dielectrophoresis (“DEP”). DEP may be used for the manipulation, separation, and collection of cells, viruses, biomolecules and nanoparticles. AC voltages may be used to pull water droplets into a gap between liquid siphons, and similar techniques may be used to move water droplets on solid surfaces. T. B. Jones, M. Gunji, M. Washizu and M. J. Feldman, J. Appl. Physi. 89, 14A-F41-14A-F48 (2001) Dielectrophoretic liquid actuation and nanoddroplet formation .; T. B. Jones, Electrostat. 51, 290-299(2001) Liquid dielectrophoresis on the microscale .; M. Washizu, IEEE T. Ind Applic. 34, 732-737 (1998). Electrostatic actuation of liquid droplets for miroreactor applications .; M. G. Pollack, R. B. Fair, A. D. Shenderov, Appl. Phys. Lett. 77, 1725-1726 (2000) Electrowetting - based actuation of liquid droplets for microfluidic applications . Parallel electrodes can be used that operate directly on water droplets that are placed on a solid surface. The droplets can be drawn between the electrodes because of the high dielectric permittivity of water. Relatively high voltages and/or high frequencies may be required, which can lead to significant power dissipation, heating of the aqueous phase, and evaporation. In addition, the droplets are generally in direct contact with a solid surface, such as plastic or glass. Thus, many of the problems discussed above with respect to surface fouling, evaporation, chip contamination, etc. may also be present.
SUMMARY OF THE INVENTION
In some embodiments according to the present invention devices are provided for the manipulation of a suspended particle in an electric field gradient. A plurality of electrically isolated electrodes are positioned on a surface. A liquid composition is on the plurality of electrodes. The liquid composition covers the surface continuously between adjacent ones of the plurality of electrodes. The liquid composition has an exposed liquid surface for suspending a particle. The plurality of electrodes are configured to provide an electric field gradient for transporting the particle suspended in said liquid composition.
In this configuration, particles, such as droplets, can be transported without contacting solid surfaces. Surface fouling, evaporation, chip contamination, power dissipation, and heating can be reduced.
Further embodiments according to the present invention provide methods for the manipulation of a suspended particle in an electric field gradient. A plurality of electrodes are configured on a surface to provide an electric field gradient for transporting a particle. A liquid composition is applied on the plurality of electrodes. The liquid composition has an exposed liquid surface for suspending a particle. The particle is suspended in the liquid composition. A voltage is applied between selected ones of the plurality of electrodes to provide the electric field gradient. The electric field gradient defines a pathway for transporting the particle.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1A is a perspective schematic drawing of an electrode series for manipulating droplets on a substrate according to embodiments of the present invention.
FIGS. 1B-1C are side views of electric fields with gradients produced by electrodes submerged in a fluid having a droplet suspended therein according to embodiments of the present invention.
FIGS. 1D-1H are top views of electrode configurations according to embodiments of the present invention.
FIGS. 2A-2B are top views of equilibrium positions of 750 nL droplets on an electrode array according to embodiments of the present invention.
FIG. 2C is a colloidal crystal formed on the upper surface of a droplet according to embodiments of the present invention.
FIG. 2D is a confocal microscopy three-dimensional reconstruction of a droplet containing 0.2 wt. % fluorescent latex where nearly all of the particles are concentrated on the droplet top surface according to embodiments of the present invention.
FIGS. 3A-C are top views of two droplets ( FIG. 3A ) that are combined and mixed ( FIGS. 3B-C ) on a fluid-fluid electrode chip according to embodiments of the present invention.
FIG. 3D is a micrograph of the combined droplet that results after two droplets containing polystyrene (white) and magnetic (brown) latex have been mixed to temporarily form anisotropic polymer aggregate according to embodiments of the present invention.
FIG. 3E is a micrograph of a crystalline shell of calcium phosphate precipitated after mixing droplets containing solutions of Na 2 HPO 4 and CaCl 2 .
FIG. 3F is a micrograph of a water droplet containing 1.0 wt. % latex and 1.9 nM Na-dodecyl sulfate encapsulated inside a liquid dodecane shell.
FIG. 4 is a schematic drawing of an examplary design of electrodes and their connecting leads in a fluid-fluid chip according to embodiments of the present invention.
FIG. 5 is a graph of the droplet speed as a function of the squared field intensity for 750 nL aqueous droplets submersed in a 1.15 mm deep PFMD layer according to embodiments of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
The present invention now will be described more fully hereinafter with reference to the accompanying drawings, in which various embodiments of the invention are shown. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. In the drawings, the relative sizes of elements may be exaggerated for clarity. Like reference numerals in the drawings denote like members.
When an element is described as being formed “on” or “adjacent to” another layer or element, the element may be formed directly on the other layer or element, or other elements or layers may be interposed therebetween. In contrast, when an element is referred to as being “directly on” another element, there are no intervening elements present. The thicknesses of elements, layers or regions may be exaggerated for clarity.
Embodiments according to the present invention provide devices and methods for manipulating droplets. With reference to a device 10 shown in FIG. 1A , electrodes 14 A-F are positioned in series on a substrate 17 . A fluid 16 , such as oil, is applied on the electrodes 14 A-F, and droplets 12 are suspended in the fluid 16 . Electric leads 18 are connected to the electrodes 14 A-F and a power source (not shown) to provide a voltage to the electrodes 14 A-F. The fluid 16 has an exposed surface 16 A that is in open contact with the surrounding air. As illustrated, the droplet 12 is not in contact with any of the solid surfaces of the device 10 , such as the solid surfaces of the electrodes 14 A-F or the substrate 17 . In this configuration, surface fowling, evaporation, adsorption of the droplet 12 (or components carried by the droplet 12 ), and chip contamination may be reduced.
Various types of fluids can be used for the fluid 16 , such as perfluorinated oil, silicone oil, fluorocarbons, hydrocarbons, and/or combinations thereof. For example, perfluorinated hydrocarbons, or other inert, benign liquids with a low dielectric permittivity that is denser than water, can be used. The droplets 12 can be water droplets or hydrocarbon droplets. In some embodiments, the fluid 16 can be a hydrocarbon fluid and the droplets 12 can be formed of a perfluorinated oil suspended therein, i.e., an oil/oil suspension. The substrate 17 can be any solid material, and the substrate 17 does not require any particular surface treatment with respect to smoothness, wetting, etc. Although embodiments of the present invention are described herein with reference to droplets, it should be understood that solid particles can also be suspended in a fluid surface (e.g., fluid 16 ). Solid particles can result from precipitations of liquid droplets on the fluid surface, or solid particles can be deposited directly on the fluid surface. Liquid droplets of various viscosities can also be transported on a fluid surface. Moreover, the droplets can include other components, such as nanoparticles, microparticles, surfactants, protein, cells, viruses, polymers, polymerizable monomers, surfactants, silicone compounds, and/or combinations thereof. Such components can be included in the droplets 12 in any form by which the component can be carried, such as in solutions, suspensions, dispersions, micro-emulsions, emulsions, etc. The droplets 12 can be between about 0.01 μL and about 10 μL.
As shown in FIG. 1 , the suspended droplets 12 can be driven by alternating currents (AC) and/or direct currents (DC) applied to the electrodes 14 A-F. Alternating current can be provided at between about 50V and about 500 V at a frequency between about 50 Hz and about 500 Hz. Exemplary ranges of DC voltages are between about 20 V And about 500V. The electrodes 14 A-F are arranged in series and are electrically isolated from one another by the substrate 17 . The electric field patterns created by the electrodes 14 A-F allow controlled droplet motion along predetermined pathways. The electrodes 14 A-F can be individually addressable by a controller, and typically, the electrodes 14 A-F that are not switched to the high voltage source are grounded.
As described in more detail below, movement of multiple droplets can be controlled using electrodes, such as the electrodes 14 A-F in FIG. 1A , that provide an electric field gradient along one or more pathways. In some embodiments, the electrodes can be configured to provide two or more pathways that may intersect to combine droplets. Droplets can be combined on a single pathway by transporting droplets in opposite directions or in arbitrary directions on electrode arrays. Combined droplets can be used to provide various types of microassays, including assays known to those of skill in the art. For example, bioassays can be provided, which include microsphere agglutination or fluorescence assays for proteins DNA, RNA, viruses or other biologically specific markers. As another example, viability assays can be used to detect the viability status of cells, bacteria or viruses in droplets by mixing a droplet containing the cell, bacteria, or virus of interest with a droplet containing a toxin, virus, protein, or other disease-causing agent. Drug screening microassays may involve determining the viability status of cells, bacteria or viruses after mixing a droplet containing the cell, bacteria, or virus with a droplet(s) containing the drug and/or a disease-causing agent. Chemical microassays can be performed such that the status of a certain chemical reaction is expressed by a change in color, precipitation, opalescence, or fluorescence after two droplets are mixed. Assays according to embodiments of the present invention can be used to detect toxins, chemical agents, environmental contaminants, detergency actions, etc. Mixing, drying or polymerization reactions can lead to the synthesis of advanced materials in the form of anisotropic or otherwise organized particles. Examples of such preparation and application of droplets and/or particles are given in O. D. Velev, K Furusawa, K. Nagayama, Langmuir 12, 2374 (1996); O. D. Velev and K. Nagayama, Langmuir 13, 1856 (1997); O. D. Velev, A. M. Lenhoff, E. W. Kaler, Science 287, 2240-2243 (2000), the disclosures of which are hereby incorporated by reference in their entireties.
Electrodes according to embodiments of the present invention can be configured in various shapes and positioned in various arrays to provide a desired electric field to manipulate motion of a droplet. Without wishing to be bound by any particular theory, in some embodiments, the application of a spatially inhomogeneous AC on electrodes can provide a dielectrophoretic (DEP) force, F DEP , which acts in the direction of the gradient of the squared electric field, ΔE 2 , and which can be described by the following equation.
{right arrow over (F)} DEP =2πε 1 Re | K ( w ) | r 3 ΔE 2
where r is the radius of the particle (e.g., the droplet 12 in FIG. 1A ), ε 1 is the dielectric permittivity of the media (e.g., the fluid 16 ), and K is the Clausius-Mossotti factor. The direction and magnitude of the DEP force depend on the real part of K, which in the example given in FIG. 1A is the effective polarizability of the droplet 12 and is generally higher than droplets in a continuous liquid media, such as in microchannel devices. The droplets 12 can also be attracted and repelled by constant DC fields applied to the electrodes 14 A-f The forces operating in this case include common electrostatic (Coulombic) attraction and repulsion. These forces are possible because the droplets posses charge, and/or dipole moment.
The equilibrium position of one of the droplets 12 with respect to the electrodes depend on the pattern and/or frequency of the voltage on the electrodes 14 A-F. As shown in FIG. 1A , electrodes 14 A, 14 C, 14 D, and 14 F are grounded, and electrodes 14 B and 14 E are provided with AC power. Further examples of electrodes and electrode field gradients are shown in FIGS. 1B-1C , in which electrodes 24 A- 24 D, 34 A- 34 D are submerged in fluids 26 , 36 , respectively. The fluids 26 , 36 each have an exposed surface 26 A, 36 A in contact with surrounding air 20 , 30 . Droplets 22 , 32 are suspended in the fluids 26 , 36 and manipulated by the electric field gradients provided by the electrodes 24 A- 24 D, 34 A- 34 D. Electrodes 24 C, 24 D, 34 A, 34 C, and 34 E are grounded, and electrodes 24 A, 24 B, and 34 B are connected to an AC power source. In FIGS. 1A-C , the droplets 12 , 22 , 32 can be water droplets and the fluids 16 , 26 , 36 can be perfluorinated hydrocarbon oil (F-oil). Water droplets can be attracted along the electric field gradient produced by the electrodes 14 A-F, 24 A-D, 34 A-D to regions of high field intensities because water droplets have a higher dielectric permittivity and conductance than F-oil.
For example, as shown in FIG. 1B , the electrodes 24 A- 24 D are connected in sequences of two energized electrodes 24 A, 24 B and two grounded electrodes 24 C, 24 D. The droplet 22 migrates to the gap between the energized electrodes 24 A, 24 B and the non-energized electrodes 24 C, 24 D because the droplet position at this gap is in close proximity to the area of highest field intensity. On the other hand, if a single energized electrode is positioned between grounded electrodes, the electric field gradients can position the droplet substantially above the energized electrodes. As shown in FIG. 1A , the droplets 12 are positioned above the energized electrodes 14 B, 14 E, and in FIG. 1C , the droplet 32 is positioned above the energized electrode 34 B. The trapped droplets 12 , 32 can be moved by consecutively switching on and off the voltage to the various electrodes 14 A- 14 F, 34 A- 34 D.
Electrodes according to embodiments of the present invention can be shaped in various configurations. For example, the electrodes can be conductive rings having an interior void, such as the circular ring electrodes 40 shown in FIG. 1D or the square ring electrodes 42 shown in FIG. 1E . Pairs of electrodes can also be used to provide a desired electric field gradient, such as the “herringbone” configuration of electrode pairs 44 A, 44 B shown in FIG. 1F . The electrodes can be arranged in an array to provide pathways along which a droplet can be transported. For example, in FIG. 1G , electrodes 46 A define one pathway and electrodes 46 B define another pathway. Electrodes 46 D define still another pathway. The electrode pathways intersect at electrode 46 C. The configuration shown in FIG. 1G can be used to combine or divide one or more droplets. For example, droplets transported along electrodes 46 A from left to right and droplets transported along electrodes 46 B from left to right can be combined with one another at the intersection electrode 46 C. On the other hand, the voltages applied to the electrodes 46 A-D can be selected such that droplets can be transported along electrodes 46 from right to left and separated into two droplets at intersection electrode 46 C. One of the resulting droplets is transported away from electrode 46 C along electrodes 46 A, and the other droplet is transported away from electrode 46 C along electrodes 46 B. As another example of an electrode configuration that can be used to combine droplets with reference to FIG. H, electrode pairs 48 A, 48 B, 50 A, 50 B, 52 A, 52 B can be used to combine one droplet 54 A from electrode pair 48 A, 48 B with another droplet 54 B from electrode pair 50 A, 50 B. The combined droplet 54 C can be further transported by an additional electrode pair 52 A, 52 B. The electrodes can also be combined in a two-dimensional array so that a droplet can be moved in horizontal, vertical, or diagonal directions, depending on which of the surrounding electrodes are energized by the controller.
In some embodiments, the electrodes described in the examples above can have a length of between about 0.1 and about 1 mm and a distance between electrodes in a given array of between about 0.1 mm and about 1 mm.
The following non-limiting examples are provided to illustrate various embodiments according to the present invention in detail.
EXAMPLE 1
Fluid-Fluid Droplet Transport Devices
Electrodes and electrical leads were fabricated on two-sided printed circuit boards that have electrodes on one side and connecting leads on the other. An exemplary device 70 is shown in FIG. 4 . An array of electrodes 78 is arranged on a circuit board substrate (not shown). The electrodes 78 are connected to a controller 74 by leads 76 , 76 A, 76 B. As illustrated, the leads 76 A pass above the circuit board and leads 76 B (dashed lines) pass below the circuit board. A controller 74 that includes a power source 72 controls power to the electrodes 78 . The power source 72 can be an AC and/or a DC power source. The controller 74 can also include a computer controlled switch box, and amplifier, and/or a signal generator for controlling the signals to the electrodes 78 .
The electrode boards were immersed inside 50 mm Petri dishes filed with perfloromethyldecaline (PFMD). The electrode leads were connected through a computer controlled switch box to an amplifier a signal generator. Electrodes that were not switched to a high voltage amplifier output were grounded. The transition between AC to DC signals could be made gradually be varying the symmetry ratio of the AC waves, from full negative, to symmetric AC, to full positive voltage. Some droplets were formed from aqueous suspensions of polystyrene latex microspheres that were purchased from Interfacial Dynamics Corp. (OR). Other droplets contained gold nanoparticle suspensions that were synthesized by citrate reduction of auric acid in the presence of tannic acid.
As shown in FIGS. 2A-D and 3 A-D, droplets were suspended in the PFMD oil of a device as describe above and transported by AC and/or DC currents applied to the arrays of individually addressable electrodes. The droplets included water or dodecane droplets having a volume of about 500-100 nL, which were formed by micropipette and suspended at the oil/air interface without contact with the electrodes. Some of the water droplets used contained suspensions of micro- and nanoparticles as described above. The droplets were driven with AC or DC voltages in the range of 200-600 V. The AC frequencies were in the rang of 50-5000 Hz.
FIG. 2A illustrates the initial equilibrium positions of four droplets 50 A-D on an array of electrodes 52 . Every fourth electrode beginning from the left side of the picture is energized. The droplets 50 A-D contain fluorescent latex microparticles (droplet 50 A), gold nanoparticles (droplet 50 B), white latex (droplet 50 C), and magnetic latex (droplet 50 D). FIG. 2B illustrates another position of the droplets after three cycles of switching the electrodes 52 to the right. The scale bar 54 is 1 mm.
As illustrated, multiple droplets containing different nano-particles (or other components), can be transported on chips with a large number of individually addressable electrodes. The droplets can be directed along the desired track by switching electrodes, and electric field gradients can be configured to combine or separate the droplets. The two-dimensional matrixes of individually addressable electrodes can allow independent positioning, movement in a desired direction, mixing of droplets of various compositions, and/or the separation of a droplet into two droplets.
EXAMPLE 2
Parameter Effects
The effects of basic system parameters on droplet mobility in the devices described in Example 1 are summarized in Table 1 below.
TABLE 1
Effect of the experimental parameters on the responsiveness and mobility of the
suspended microdroplets.
Factor
Range studied
Effect on droplet responsiveness
AC field
Symmetric square waves
Moves water droplets towards areas of
highest field intensity (FIG. 1A-B).
DC bias
0-500 V
Attraction or repulsion, followed by recharging.
Moves both water and oil
droplets. Very strong, but erratic.
AC amplitude
0-600 V
Increases (↑) proportionally to E 2
AC frequency
50-5000 Hz
None
Droplet volume
500-1500 nL
↑
Distance between droplet bottom
0.01–0.5 mm
Decreases (↓)
and chip surface
Electrolyte in water droplets
None added - 0.1 M
(↑) Small
Fluorinated or non-fluorinated
0-0.1 wt. %
None
surfactant added in droplet
Full immersion of the droplets in
—
↓↓ Could lead to complete loss of
overlying dodecane layer
responsiveness
Electrode geometry
Square or circular
Square electrodes more effective at
shorter drop-electrode distance, circular
at larger
EXAMPLE 3
Particle Crystallization
Internal polarization of droplets, such as the droplets described in Example 1, may be evidenced by observing the vertical distribution of particles contained inside the droplets. Negatively charged latex microparticles inside a droplet can migrate and accumulate on the side of the droplet cap that protrudes above the fluid in which the droplet is suspended. Color diffraction from the concentrated particle phase directly below the droplet surface may be observed, which may indicate that the particles on top can become concentrated to the point of colloidal crystallization. FIG. 2C illustrates colloidal crystals formed on the upper surface of a droplet containing 20 wt. % of sulfate latex. The droplet is suspended in oil, and the upper surface of the droplet is exposed to air above the oil/air interface. The particles have crystallized because of attraction to the top surface. FIG. 2D is a confocal microscopy three-dimensional reconstruction from above the droplet in FIG. 2C illustrating that nearly all of the particles are concentrated at the top surface. The scale bar 56 is 500 μm.
The asymmetric dielectric environment can provide this polarization of particle distribution. In contrast, when a thick layer of dodecane was poured on top of the perfluorinated hydrocarbon oil so that the droplets were immersed in a media with uniform dielectric constant, the particles remained essentially uniformly dispersed. The concentration of particles at the upper surface of a droplet may be used in droplets that are carriers for micro- and nanoparticles and living cells because it allows their contents to be thus separated and clearly visible on the top side of the droplet.
EXAMPLE 4
Droplet Mixing
FIGS. 3A-C illustrate the mixing, precipitation, and encapsulation in aqueous microdroplets suspended on a matrix fluidic chip. An electrode array 68 A is submerged in oil as described in Example 1. A droplet 62 containing magnetic latex and a droplet 64 containing polystyrene are suspended in the oil in FIG. 3A . As shown in FIG. 3A , the droplets 62 , 64 are transported along two respective pathways and combined at an intersection between the pathways to form a combined droplet 66 . The combined droplet 66 can be further transported as shown in FIG. 3C .
A two-dimensional matrix electrode array 68 B having a droplet 62 B thereon is shown in FIG. 3D . The electrodes of the two-dimensional matrix array 68 B are spaced such that a droplet can be moved vertically, horizontally, and/or diagonally. The electrode array 68 B has been submerged in oil as described in Example 1. As illustrated, the droplet 62 B is the result of a combination of a droplet containing polystyrene (white) and another droplet containing magnetic (brown) to temporarily form an aniosotropic polymer aggregate. That is, when particles carried inside droplets were allowed to segregate to the top of the droplet prior to mixing, intermittent anisotropic clusters of particles formed on the surface of the newly combined particle 62 B, as shown in FIG. 3D . Because fluidic chips according to embodiments of the invention can provide massive parallelization, such chips can be used for automated fabrication of functional micro- and nano-assembiles, such as “supraparticles” with colloidal crystal structure. The scale bar 60 A is 1 mm.
EXAMPLE 5
Droplet Mixing and Precipitation
A variety of mixing and precipitation experiments were performed by controllably merging pairs of droplets of different compositions, such as those described with respect to FIGS. 3A-D on a chip as described in Example 1. The complex precipitation patters inside the mixed droplets can lead to the formation of crystal shell-like balls. These particles have a water core inside and could be further moved intact along the electrodes. Such shell-like crystalline particles may be used, e.g., as biomimetic capsules. FIG. 3E shows a crystalline shell of calcium phosphate precipitated after mixing droplets containing solutions of Na 2 HPO 4 and CaCl 2 . The scale bar 60 B is 1 mm.
Water and hydrocarbon droplets on the chips were combined in a 1:1 ratio. The droplets can be mixed as described with respect to droplets 62 , 64 in FIGS. 3A-C . When a surfactant, such as sodium dodecyl sulfate, was added to the water droplets, the interfacial tensions balance can favor the complete engulfment of the water droplet in the hydrocarbon droplet. The water droplets became symmetrically encapsulated inside a liquid hydrocarbon shell. FIG. 3F illustrates a water droplet containing 1.0 wt. % latex and 1.9 mM Na-dodecyl sulfate encapsulated inside a liquid dodecane shell. The scale bar 60 C is 1 mm.
EXAMPLE 6
Power Dissipation
The devices and methods described in Examples 1-5 were used to transport various droplets using various electrode patterns. The maximum speed at which droplets can be moved by switching AC power to the electrodes may be approximately proportional to E 2 , as provided by the above formula for F DEP , which was verified experimentally. Power dissipation (also verified experimentally) may be relatively low because the currents through the electrode may be smaller than the capacitance leaks in the circuit. It has been estimated that the energy needed to transport a suspended droplet in some embodiments of the invention can be on the order of 1 × 10 −9 J/cm for droplets having a volume of between about 500 and 1000 nL. In contrast, the energy required to move a similar droplet size on a solid surface or in microfluidic channels may be two orders of magnitude greater.
A liquid-liquid microfluidic chip as described in Example 1 was prepared. An estimate for the energy required to move a 500 nL water droplet 1 cm at 2 mm/s using the chip as described in Example 1 is compared to estimates for energies for transporting similar droplets by conventional microfluidics with channels in Table 2.
TABLE 2
Droplet moved in
Hemispherical droplet
Viscous flow in
F-oil
dragged on solid surface
microfluidic channel
Assumptions and
Stokes sphere
θ Advancing = 90 deg
Circular channel
approximations
in bulk liquid
θ Receding = 80 deg
of diameter 20 μm
No viscous
Poiseuille flow
dissipation
Type of estimation
Overestimate
Underestimate
Underestimate
Energy required/J
≦9.4 × 10 −10
≧1.6 × 10 −7
≧1.4 × 10 −4
Energy ratio
1
170
150000
EXAMPLE 7
Electric Fields and Energy
Various electric fields can be provided to obtain the desired movement of droplets. For example, AC power can be used as discussed above or droplets can also be transported using a DC power source to provide constant electrical voltages. Water droplets may respond strongly to DC fields by either moving rapidly away from an energized DC electrode, or by being strongly attracted towards it. The velocity of droplet motion and the range of the interactions may be larger than the AC-driven effects at the same voltage range. For example, the velocity can be twice as large and reach speeds of 2.0 mm/s or higher. This speed may be due to the water droplets having a significant charge and/or dipole moments that respond to Coulombic repulsion or attraction. The sign of the charge of a droplet made from various suspensions can vary from positive to negative. The droplets may be charged by collecting static charges from the interface of the fluid in which the droplet is suspended and/or from a charge transfer through the fluid phase. Furthermore, charging and/or re-charging effects may be observed at combined AC+DC voltages. The use of DC fields can be used to manipulate other droplets, such as hydrocarbon oil droplets. These droplets may not respond to symmetric AC fields due to a lack of polarizability because their dielectric permittivity is close to that of PFMD. However, hydrocarbon oil droplets may respond to a constant field in a manner similar to water droplets.
EXAMPLE 8
Droplet Velocity
The speed of a droplet placed on devices described in Example 1 was measured. The droplet was a 750 nL aqueous droplet submersed in a 1.15 mm deep PFMD layer. The speed was measured by the shortest time required for the droplet to traverse an automated eight electrode sequence in a forwards and backwards direction. The field was estimated by dividing the voltage applied by the electrode pitch, which was 1.54 mm. The AC frequency was 200 Hz. The droplet speed as a function of the field intensity squared is shown in FIG. 5 .
Embodiments of the present invention described herein can be combined with existing electrowetting and channel microfluidics techniques in larger integrated devices. This can be used for automatic droplet dispensing onto the fluorinated oil surface. For example, the existing techniques for droplet breakup and manipulation by electrowetting on solid surfaces [see, e.g., T. B. Jones, M. Gunji, M. Washizu and M. J. Feldman, J Appl. Physi. 89, 14A-F41-14A-F48 (2001) Dielectrophoretic liquid actuation and nanodroplet formation .] could be used to break up droplets from a larger volume of liquid at the edge of the chip. This can automate the procedure of droplet deposition on the surface of the liquid, which may also be done by a micropipette. Droplets can then be further manipulated as described herein. Similarly, common microfluidic channels can be used for liquid transport to a chip and droplet breakup. The removal of droplets from liquid surfaces and their collection and/or disposal can also be performed by using electrowetting or microfluidic channels.
In the drawings and specification, there have been disclosed typical embodiments of the invention and, although specific terms are employed, they are used in a generic and descriptive sense only and not for purposes of limitation, the scope of the invention being set forth in the following claims. | Devices for the manipulation of a suspended particle in an electric field gradient include a plurality of electrically isolated electrodes on a surface. A liquid composition is on the plurality of electrodes. The liquid composition covers the surface continuously between adjacent ones of the plurality of electrodes. The liquid composition has an exposed liquid surface for suspending a particle. The plurality of electrodes are configured to provide an electric field gradient for transporting the particle suspended in said liquid composition. | 1 |
The present invention relates to a sorting device for sorting products, comprising successive load carrying platforms having a front edge and a rear edge for supporting products to be sorted on a supporting surface thereof, conveying means for conveying the load carrying platforms in a conveying direction along a conveying path, sorting means comprising a plurality of pusher elements for pushing a product to be sorted sideways off at least one supporting surface at a desired sorting location using at least one pusher element which pusher elements each extend above at least part of said at least one load carrying platform and which are arranged for being jointly conveyed with said at least one load carrying platform in the conveying direction, and drive means for moving said at least one pusher element sideways at a desired sorting location.
BACKGROUND OF THE INVENTION
In 2007, a sorting system called BAXORTER, in particular for automated luggage handling, was put on the market by Vanderlande Industries Nederland B.V. Said known sorting system makes use of an endless train of rectangular load carrying platforms having a length of about 1.2 m, directly above which sorting beams are provided, which can be mechanically controlled at a sorting location to move from one longitudinal side to the other longitudinal side of the load carrying platform and push a product present on said load carrying platform, for example a piece of luggage, off the load carrying platform upon making said movement. Closing plates are provided between the load carrying platforms at both ends of each load carrying platform, the object of said closing plates being to fill the space between load carrying platforms so as to prevent objects getting between the load carrying platforms, which could lead to damage and malfunctions. The closing plates of adjacent load carrying platforms overlap and are provided with a curved outer edge oriented towards the respective adjacent load carrying platform, the curved outer edges of which overlapping closing plates cross one another. The aforesaid arcuate shape is necessary in order to be able to pass through bends. Because of the aforesaid arcuate shape, a triangular surface is present between the overlapping closing plates on the two opposite outer sides thereof, which surface is not screened by the closing plates themselves and which may need to be screened separately by further closing elements that are movable with respect to one or both closing plates. All in all, several measures need to be taken to realise a so-called closed deck as much as possible so as to reduce the risk of objects, for example straps of pieces of luggage, getting under or between the load carrying platforms. The object of the present invention is in any case to provide a constructionally relatively simple solution for realising a closed deck in sorting devices of the kind referred to in the introduction.
Since many years, Vanderlande Industries Nederland B.V. have furthermore marketed a sorting system under the name of POSISORTER. Said sorting system makes use of transversely oriented carriers arranged relatively close behind each other, along which pusher shoes are movable in the longitudinal direction of the carriers, so that products, such as packages, present on a number of successive carriers can thus be pushed off said carriers by the pusher shoes at a sorting location. The carriers follow an endless path in a vertical circuit. Only the upper half of said circuit can be utilised for sorting products. In said upper half, as in the lower half for that matter, the carriers follow a rectilinear conveying path. To increase the sorting capacity, EP-A1-782 966 discloses a comparable sorting system comprising carriers and pusher shoes movable along the carriers, with the endless circuit extending in the horizontal plane. So far it has not been possible, however, to be commercially successful on the market with such a system. The object of the invention is furthermore to provide an alternative to sorting systems such as the POSISORTER which has commercial possibilities, which alternative distinguishes itself in that the entire length of the conveying path can be utilised and wherein, in addition, the aforesaid closed deck principle is maintained not only in rectilinear parts of the conveying path but also in curved parts.
SUMMARY OF THE INVENTION
In order to accomplish the above objects, both the front edge of each load carrying platform and the rear edge of each load carrying platform are arcuate in shape, seen in top plan view, with the arcuate shape of the front edge of a load carrying platform abutting the arcuate shape of the rear edge of a next load carrying platform located at the front of the respective load carrying platform. Because of the aforesaid arcuate shape of the abutting edges of adjacent load carrying platforms, each load carrying platform can pivot with respect to an adjacent load carrying platform about a pivot axis that coincides with the centre of the arcuate shape in question without the closed nature of the transition between the respective load carrying platforms being lost. Add to this the fact that precisely because of the arcuate shape, the gap between the load carrying platforms, which is practically inevitable and which is logically arcuate in shape as well, reduces the risk of objects getting between the load carrying platforms in comparison with a rectilinear gap that would have the same width.
To simplify the drive of the pusher elements, the drive means preferably comprise at least one driver for each pusher element, which driver is connected to an associated pusher element via connecting means. Each pusher element can thus be driven via said at least one driver.
The aforesaid connecting means preferably extend through at least one through slot in the at least one associated load carrying platform. The pusher elements and the associated drivers can thus be arranged comparatively close together, thus making it possible to use connecting means of very simple design as well. The use of a through slot in a load carrying platform in principle involves the risk of objects getting jammed in the slot. Tests have shown, however, that in practice this risk is limited and, in addition, can be further reduced by taking additional measures, for example providing brushes which extend within the slot, along which the connecting means can move.
In particular if the sorting device according to the invention is designed for using only one pusher element for each product to be sorted, the pusher element in question needs to have dimensions approximately equal to the dimensions of the product to be sorted, seen in the conveying direction. As the dimensions in question increase, it will be advantageous if the sorting means comprise two drivers for each pusher element, which drivers are each connected at different positions to the associated pusher element via the connecting means, so that a single pusher element can push a product off an associated load carrying platform in a stable manner at a sorting location.
It is furthermore preferable in that connection if a slot is provided in said at least one associated load carrying platform for each of the two drivers, through which slot the associated connecting means extend.
The two slots in question are furthermore preferably provided in two different load carrying platforms. The dimensions of the load carrying platforms can thus remain limited, at least in the conveying direction, whilst nevertheless comparatively long pusher elements can be used, by means of which comparatively large products, such as packages or pieces of luggage, can be individually sorted. The advantage of using load carrying platforms having limited dimensions is that it is possible to pass through comparatively sharp bends.
The above positive effects can be further enhanced if at least one intermediate load carrying platform is provided between the two different load carrying platforms provided with the respective slots, which at least one intermediate load carrying platform is furthermore preferably free from slots, so that the intermediate load carrying platform is easier and thus cheaper to produce. In addition, the risk of objects getting jammed in the sorting device is thus further reduced.
To compensate for the change in the spacing between the two slots associated with a single pusher element when passing through bends, it is preferable if the pusher element comprises at least two pusher element parts which are telescopically movable relative to each other for the purpose of changing the length of the pusher element, and/or if the pusher element is connected to at least one of the associated pusher elements by the connecting means in such a manner as to be movable in a longitudinal direction of the pusher element.
Said at least one slot is preferably oriented perpendicular to the conveying direction, so that the slot takes up as little length of the associated load carrying platform as possible and the pusher element will furthermore not move in the conveying direction with respect to the load carrying platform during movement of the moving means.
A very suitable way of driving the pusher elements is obtained if the drive means comprise a stationary guide oriented at an angle relative to the conveying direction at the sorting location, with which stationary guide said at least one driver can be selectively caused to interact.
Alternatively it may also be very advantageous if the drive means comprise at least one driving motor for each pusher element, which driving motor is connected to a load carrying platform associated with the pusher element for joint transport in the conveying direction with the respective load carrying platform, thus providing a much greater degree of freedom with regard to the exact position where the drive means are operative, and rear the actual sorting process takes place, therefore.
According to a very important preferred embodiment, adjacent load carrying platforms are arranged in line with each other. Thus, one large joint supporting surface is created along the full length of the conveying path along which the sorting device moves.
In order to further reduce the risk of objects getting jammed in gaps formed between abutting front and rear edges of the adjacent load carrying platforms, it is preferable if adjacent load carrying platforms overlap at the location of the associated abutting front and rear edges, in which case adjacent load carrying platforms are arranged in line with each other, as described with reference to the preceding preferred embodiment.
From a practical point of view, said overlap can be realised in an advantageous manner if the abutting front and rear edges have a complementary stepped configuration, seen in vertical section parallel to the conveying direction and/or if the abutting front and rear edges have a parallel inclined configuration, seen in vertical section parallel to the conveying direction. An overlap realised in this way makes it possible in a relatively simple manner, in spite of the overlap, to remove a single load carrying platform from the train of load carrying platforms and replace it by another load carrying platform.
An alternative solution to the problem of the risk of objects getting between adjacent load carrying platforms is realised if successive load carrying platforms are provided with aligned grooves at their facing sides, in which a (preferably strip-shaped) closing element is provided. Such a closing element not only provides a closure, but it can also provide a correct vertical alignment of the adjacent load carrying platforms relative to each other.
A very suitable way of driving the sorting device as a whole is realised if the conveying means comprise an elongated flexible conveying element under the load carrying platforms, which conveying element is provided with links which can pivot about vertical pivot axes relative to each other, whilst each load carrying platform is connected to a link.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will now be explained in more detail by means of a description of two preferred embodiments of a sorting device according to the invention, in which reference is made to the following figures:
FIG. 1 is a perspective view of part of a sorting device according to a first preferred embodiment of the invention;
FIG. 2 is a top plan view, with transparent load carrying platforms, of part of the sorting device of FIG. 1 ;
FIG. 3 a is a top plan view of part of the sorting device of FIG. 1 during operation;
FIG. 3 b is a side view of part of the sorting device of FIG. 3 a;
FIG. 4 is a top plan view of a second preferred embodiment of the sorting device according to the invention;
FIG. 5 is a top plan view of the sorting device of FIG. 4 passing through a bend;
FIG. 6 a is a vertical sectional view along the line VI-VI in FIG. 4 at the transition between two successive load carrying platforms;
FIG. 6 b is a sectional view corresponding to FIG. 6 a of an alternative embodiment; and
FIG. 6 c is a sectional view corresponding to FIG. 6 a of another alternative embodiment.
FIG. 7 is a top plan view corresponding to FIG. 2 of an alternative embodiment.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1 shows part of a sorting device 1 according to a first preferred embodiment of the invention. The sorting device 1 comprises a chain 2 . The chain 2 comprises links 3 , which are pivotally connected about vertical pivot axles 4 . A guide wheel 5 is provided for each link 3 , the central axis of which guide wheel coincides with that of an associated pivot axles 4 . The guide wheels 5 run in a U-shaped guide (not shown), which extends in an endless conveying path. Provided at the upper side of each link 3 is furthermore a transversely oriented supporting arm 6 , with running wheels 7 mounted to two opposite ends thereof, the central axes of which running wheels are oriented transversely to the conveying direction 9 of the sorting device 1 and in line with each other. The running wheels 7 run on rails (not shown), which extend parallel to the conveying path defined by the U-shaped guides the guide wheels 5 .
Furthermore, a load carrying platform 10 is provided for each link. The successive load carrying platforms are in line with each other. Each load carrying platform 10 is more or less moon-shaped. The circumference thereof is defined by two at least substantially straight side edges 11 , an arcuate front edge 12 and a likewise arcuate rear edge 13 . The edges 12 , 13 have an angle of arc of about 95 degrees. Generally, said angle of arc preferably ranges between 70 and 120 degrees. At the tips 14 of the moon shape, each load carrying platform 10 is rigidly connected to a supporting arm 6 disposed thereunder, whilst each load carrying platform 10 is supported at the location of the main surface 15 by a supporting arm 6 associated with a next link 3 , which is located in front thereof, without being connected to said supporting arm 6 , so that relative movement between the load carrying platform 10 and the respective next supporting arm 6 is possible.
The radii of curvature of the front edge 12 and the rear page 13 correspond, so that the arcuate shape of the front edge of a load carrying platform matches the arcuate shape of the rear edge of a next load carrying platform 10 located at the front of the load carrying platform 10 in question. The successive load carrying platforms 10 thus form an at least substantially closed surface, or, in other words, a closed deck. This closed nature is maintained when passing through bends in the conveying path, as is shown on the right-hand side in FIG. 3 a . Upon passing through a bend, each load carrying platform 10 moves over the supporting arm 6 disposed thereunder at the location of its main surface 15 . The load carrying platforms 10 and the links 3 are so dimensioned and positioned relative to each other that the central axes of the radii of curvature of abutting front edges 12 and rear edges 13 coincide with a pivot axle 4 , as is shown in particular in FIG. 3 a.
In order to make it possible to push a product to be sorted, which is supported by one or a number of load carrying platforms 10 , off the load carrying platforms, the sorting device 1 further comprises a pusher beam 21 for every three load carrying platforms 10 . The load carrying platforms 10 provided at opposite ends of the pusher beam 21 are provided with a through slot 22 , unlike the load carrying platforms 10 located therebetween, which slot is oriented transversely to the conveying direction 9 . The slot 22 extends over substantially the entire width (this is the dimension of each load carrying platform 10 , seen in a direction perpendicular to the conveying direction 9 ) of the associated load carrying platform 10 . In an alternative embodiment, each load carrying platform might consist of two parts defining a through slot, such as the slot 22 , between them, which two parts are interconnected at the ends of the slot.
Via the slots 22 and vertical pivot axles 16 , each pusher beam 21 is pivotally connected, about the vertical pivot axles 16 , to a guide member disposed under the associated load carrying platform 10 , more specifically to a front guide member 23 and a rear guide member 24 (see FIG. 2 ). Said guide members 23 , 24 are arranged for cooperation with a guide system which is provided under the load carrying platforms 10 . For a more detailed description of said guide members 23 , 24 and the guide system, reference is made to Dutch patent application NL 1034156, the entire contents and disclosure of which are incorporated by reference herein.
Each guide member 23 , 24 comprises two guide wheels 25 , 26 , which are arranged side by side in pairs, a limited distance apart. The guide system under the load carrying platforms 10 comprises parallel rails 27 , 28 near the longitudinal sides of the load carrying platforms 10 , which rails 27 , 28 extend parallel to the conveying direction.
During normal use, when no sorting action is taking place, one of the rails 27 , 28 extends between the wheels 25 , 26 of the guide member 23 , 24 , so that the guide member 23 , 24 , and thus the associated pusher beam 21 , will move along the respective rails 27 , 28 . The rails 27 , 28 are interrupted at a sorting location 30 , at the location indicated by reference numerals 31 , 32 , so as to enable the guide members 23 , 24 to become detached from the respective rails 27 , 28 during a sorting action. In the example shown in FIG. 2 , the sorting location is arranged for pushing a product present on the load carrying platforms 10 beside a pusher beam 21 , which (initially) extends above the rail 27 , in the direction of the rail 28 . A sorting guide system 33 extends between the interruptions 31 , 32 , which system is likewise described in the aforesaid Dutch patent application NL 1034156.
It is furthermore noted that the sorting guide system 33 is interrupted halfway its length, at the location indicated at 34 , so as to enable the chain 2 to pass the sorting guide system 33 . It is furthermore worth mentioning that a switch 35 is provided in the rail 27 at the location of the interruption 31 , which switch can pivot forward and backward between two positions about a vertical pivot axle 36 . In the position shown in FIG. 2 , the switch 35 will force the guide members 23 , 24 in the direction of the sorting guide system 33 , causing the associated pusher beam 21 to cross from the side of the rail 27 to the side of the rail 28 and push a product adjacent thereto on the load carrying platforms 10 off said platforms during said transverse movement. At the location of the interruption 32 , the guide members 23 , 24 will resume their cooperation with the rail 28 again. In the position of the switch 35 that is illustrated in dotted lines, the pusher beam 21 will continue to follow the rail 27 past the switch 35 as well.
As shown in FIG. 3 a , the pusher beam 21 is telescopic, so that its length can change. This is necessary not only during the above-described sorting action when the spacing between two through slots 22 associated with a pusher beam 21 remains unchanged, but the length of the pusher beam 21 needs to change, because of the oblique orientation thereof between the slots 22 , if the guide members 23 , 24 are spaced by a fixed distance from the ends of the pusher beam 21 . Alternatively, it would also be possible to use a pusher beam 21 having a fixed length, in which case the pusher beam 21 could be slidably connected to one or both of the guide members 23 , 24 . The telescopic nature of the pusher beam 21 is also advantageous when passing through bends, as the spacing between the adjacent slots associated with a pusher beam 21 will change during said movement. For example, in the inside bend, said spacing will decrease, whereas said spacing will increase in the outside bend. This is shown in FIG. 3 a.
FIG. 4 shows a second preferred embodiment of a sorting device 41 according to the invention, which is very similar to the device 1 as described in the foregoing. The sorting device 41 comprises load carrying platforms 42 , which correspond to the load carrying platforms 10 of the sorting device 1 , at least insofar as slots 22 are present in said load carrying platforms 10 . Each of the load carrying platforms 42 of the sorting device 41 has a slot 43 that is quite similar to the slots 22 . The sorting device 41 uses a chain, such as the chain 2 , with supporting arms, such as the supporting arms 6 , for driving the load carrying platforms 42 in the conveying direction 44 . Furthermore, a guide system is provided under the load carrying platforms 42 , which guide system is quite similar to the guide system used in the sorting device 1 , i.e. comprising rails, such as the rails 27 , 28 , and a sorting guide system, such as the sorting guide system 33 .
The main difference between the sorting device 41 and the sorting device 1 is the length of the pusher beams 45 , which is significantly less than the length of the pusher beam 21 . The fact is that the length of the pusher beams 45 is nearly the same as the pitch distance of the links 3 disposed thereunder or, in other words, of the associated load carrying platforms 42 .
Only one guide member is provided for each pusher beam 45 under the associated load carrying platform 42 , which guide member is similar to one of the guide members 23 , 24 of the sorting device 1 . The guide member in question (not shown) is rigidly connected to the associated pusher beam 45 . Although it is possible in the sorting device 1 to push products off the common supporting surface defined by the load carrying platforms 42 by means of a single pusher beam 45 , the sorting device 41 is in particular suitable for pushing a product to be sorted off the load carrying platforms by means of a number of pusher beams 45 in a manner similar to the manner in which a number of pusher shoes simultaneously push products off the supporting surface in the aforesaid prior art POSISORTER.
In this embodiment, the ends of the pusher beams 45 are pointed, with inclined flanks 46 , which define a joint pushing surface 47 (indicated by a dashed line), at least during movement of the pusher beams 45 transversely to the conveying direction 44 . In addition to that, the pointed shape has the advantage that the points of adjacent pusher beams 45 will be positioned beside each other in an inside bend, as shown in FIG. 5 , thus giving each other sufficient space, in spite of the length of the pusher beams.
FIGS. 6 a and 6 b show the gap 51 that is present between two successive load carrying platforms 42 at the location of the front edge 12 and the rear edge 13 thereof. In principle said gap 51 involves a risk that objects, such as a buckle, for example, will get jammed therebetween, which may interfere with such a product being pushed off the load carrying platforms 42 . Said risk is limited precisely because of the arcuate shape of the gap 51 , to be true, but said risk can be further reduced by having the successive load carrying platforms 42 (or the load carrying platforms 10 in the sorting device 1 ) overlap at the location of the respective edges, which to that end have a complementary stepped configuration or which alternatively, as shown in FIG. 6 b , have a parallel inclined configuration.
According to another alternative embodiment, a closing or aligning element, such as the arcuate strip 61 , for example made of plastic or stainless steel, is used between two successive load carrying platforms 42 , which strip in any case extends with a limited amount of vertical clearance within aligned, facing grooves 62 in the facing short sides of the respective load carrying platforms 42 , which are for example made of wood. The function of the strip 61 is twofold, viz. preventing objects getting between the load carrying platforms 42 and aligning the two load carrying platforms relative to each other. In the present example, the grooves 62 are formed in the short sides, but alternatively they could also be created under the load carrying platforms by making use of curved angle sections, such as the angle section 63 , which is connected to the underside of a load carrying platform 42 , as is shown by way of illustration in dotted lines only for the left-hand load carrying platform 42 in FIG. 6 c , as a result of which the groove 64 could be formed. The strip 61 can be pushed into the grooves 64 from the side of the load carrying platforms 42 . Advantageously, the strips 61 are retained in the grooves 64 at their ends. Those skilled in the art will appreciate that the strips 61 do not impede the pivoting movement relative to each other.
The scope of the invention is not limited to the preferred embodiments described in the foregoing, but it is in the first place determined by the appended claims.
As an alternative to the use of a guide system disposed under the load carrying platforms, it is also possible, for example, to use one or two driving motors 70 for each pusher beam, as shown in FIG. 7 . The driving motors 70 being connected to one or two load carrying platforms. For further explanation, reference is made to Dutch patent application NL 1034940, the entire contents and disclosure of which are incorporated by reference herein. When using elongated pusher beams, such as the pusher beam 21 , with a guide member, such as the guide members 23 , 24 , at both ends, it may furthermore be decided by way of alternative to use two parallel, stationary guides for each sorting location, in which guides the respective guide members can move simultaneously and the pusher beam crosses from one longitudinal side to the other longitudinal side with its longitudinal direction parallel to the conveying direction, as is for example described in Dutch patent application NL 1033313, the entire contents and disclosure of which are incorporated by reference herein. Furthermore it might be decided to provide the two through slots, such as the slots 22 , associated with elongated pusher beams, such as the pusher beam 21 , in one and the same load carrying platform. In the latter case it is as a rule desirable to make the load carrying platforms longer. | A sorting device including successive load carrying platforms having a front edge and a rear edge for supporting products to be sorted on a supporting surface, a conveying mechanism conveying the load carrying platforms in a conveying direction along a conveying path, a sorting mechanism including plural pusher elements pushing a product to be sorted sideways off at least one supporting surface at a desired sorting location. The pusher elements each extend above at least one load carrying platform and are arranged for being jointly conveyed with the at least one load carrying platform in the conveying direction. A drive mechanism moves the at least one pusher element sideways at the desired sorting location. An arcuate shape of a front edge of a load carrying platform, as seen in top plan view, abuts an arcuate shape of a rear edge of a next load carrying platform. | 1 |
RELATED APPLICATIONS
This application claims the benefit under 35 U.S.C. 119 of European Application No. 071000054.1, filed on Jan. 3, 2007, the teachings and content of which are hereby incorporated by reference.
SEQUENCE LISTING
This application contains a sequence listing in paper format and in computer readable format, the teachings and content of which are hereby incorporated by reference. The sequence listing is identical with that incorporated in WO06/072065.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to the use of an immunogenic composition comprising a porcine circovirus type 2 (PCV2) antigen for the prevention and treatment of porcine respiratory disease complex (PRDC) in animals, preferably in pigs.
2. Description of the Prior Art
Porcine circovirus type 2 (PCV2) is a small (17-22 nm in diameter), icosahedral, non-enveloped DNA virus, which contains a single-stranded circular genome. PCV2 shares approximately 80% sequence identity with porcine circovirus type 1 (PCV1). However, in contrast with PCV1, which is generally non-virulent, infection of swine with PCV2 has recently associated with a number of disease syndromes which have been collectively named Porcine Circovirus Diseases (PCVD) (also known as Porcine Circovirus associated Diseases (PCVAD)) (Allan et al. 2006, IPVS Congress). Postweaning Multisystemic Wasting Syndrome (PMWS) is generally regarded to be the major clinical manifestation of PCVD (Harding et al., 1997, Swine Health Prod; 5: 201-203; Kennedy et al., 2000, J Comp Pathol; 122: 9-24). PMWS affects pigs between 5-18 weeks of age. PMWS is clinically characterized by wasting, paleness of the skin, unthriftiness, respiratory distress, diarrhea, icterus, and jaundice. In some affected swine, a combination of all symptoms will be apparent while other affected swine will only have one or two of these symptoms (Muirhead, 2002, Vet, Rec.; 150: 456). During necropsy, microscopic and macroscopic lesions also appear on multiple tissues and organs, with lymphoid organs being the most common site for lesions (Allan and Ellis, 2000; J Vet. Diagn. Invest., 12: 3-14). A strong correlation has been observed between the amount of PCV2 nucleic acid or antigen and the severity of microscopic lymphoid lesions. Mortality rates for swine infected with PCV2 can approach 80%.
The extent of the involvement of PCV2 in swine diseases other than PMWS is currently poorly understood (Chae, Veterinary J., 2003; 169: 326-336). There are several potentially related conditions reported in the literature including porcine respiratory disease complex (PRDC), porcine dermatopathy and nephropathy syndrome (PDNS), reproductive failure, granulomatous enteritis and potentially, congenital tremors (CT-AII) and perinatal myocarditis (Chae, Veterinary J., 2005; 169: 326-336). Among these, PRDC is considered to have the greatest economical impact in Europe due to its general high prevalence, high morbidity rate (30-70% on affected farms) and mortality rate (4-6% on affected farms) (Kim et al., Veterinary J., 2003; 166: 251-256). Pneumonia in pigs suffering from PRDC is due to a combination of both viral and bacterial agents such as PRRSV, Swine influenza virus (SIV), Mycoplasma hyopnumoniae, Actinobacillus pleuropneumoniae and Pasteurella multocida . Although the aetiology involves multiple pathogens and varies from farm to farm, PRRSV and Mycoplasma hyopneumoniae are the two most common pathogens isolated from PCV2 positive pigs exhibiting PRDC (Kim et al., Veterinary J., 2003; 166: 251-256). Whether PCV2 plays any role in the cause of PRDC or in the manifestation, severity, or prolongation of clinical signs of PRDC is yet not known.
Compared with other viral pathogens PCV2 was consistently diagnosed in lung lesions of pigs suffering from PRDC. Prospective studies have documented that pneumonia and often systemic illness, resulting from co-infection with PCV2 and PRRSV is more severe than that associated with infection by either agent alone. It can therefore be assumed that there is an apparent synergy between PCV2 and other pathogens that has been observed in respiratory disease cases in the field (Ellis et al., Veterinary Microbiol, 2004: 98: 159-163). However, it is yet not known whether PCV2, if present in pigs suffering from PRDC, has any influence on the clinical signs of PRDC in pigs. Due to the ubiquity of PCV2 with up to 100% seropositive animals at the end of fattening, it may similarly be possible that PCV2 has no influence at ad on the disease expression of PRDC but is just an unrelated co-infecting agent.
Whereas PMWS mostly affects young pigs, typically between 5 and 12 weeks of age, PRDC is predominantly seen in growing to finishing pigs, typically around 16 to 22 weeks of age. The morbidity ranges from 30-70% with an average mortality of 4-6% (Kim et al., Veterinary J., 2003; 166: 251-256). Clinically signs of PRDC are prolonged and unusually severe cough and dyspnea that is refractory to antibiotic therapy, slow growth, decreased feed efficiency, lethargy, anorexia, and a marked increase in mortality in the middle to late phase of fattening.
A hallmark of microscopic lesions PRDC is bronchointerstitial pneumonia with peribronchial and peribronchiolar fibrosis. Alveolar septa are markedly thickened by infiltrates of macrophages (Chae. Veterinary J., 2005; 169: 326-336).
Approaches to treat PCV2 infections based on a DNA vaccine are described in U.S. Pat. No. 6,703,023. In WO 03/049703, production of a live chimeric vaccine is described, comprising a PCV-1 backbone in which an immunogenic gene of a pathogenic PCV2 strain replaces a gene of the PCV-1 backbone. WO99/18214 has provided several PCV2 strains and procedures for the preparation of a killed PCV2 vaccine. However, no efficacy data has been reported. An effective ORF-2 based subunit vaccine has been reported in WO06/072065, the teachings and content of which are incorporated by reference herein. Any of such vaccines are intended to be used for the vaccination/treatment of swine or pigs older than 3 weeks of age. None of these vaccines have been described for the prophylaxis or treatment of pigs suffering from PRDC, in particular in PCV2 positive pigs, suffering from PRDC.
Moreover, such vaccines have not been described to confer protective immunity against PCV2 infection or reducing, lessening the severity of or curing any clinical symptoms associated therewith in pigs already having anti-PCV2 antibodies, preferably having maternal anti-PCV2 antibodies.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a graph illustrating body weight gain difference per week group; and
FIG. 2 is a graph illustrating development of the difference in body weight (IVP-CP) and mean virus load (log 10) over the course of the study.
DISCLOSURE OF THE INVENTION
PRDC is characterized by multiple clinical signs, including prolonged and unusually severe cough and dyspnea that is refractory to antibiotic therapy, slow growth, decreased feed efficiency, lethargy, anorexia, and a marked increase in mortality in the middle to late phase of fattening. Those clinical signs are associated with a large number of various pathogens. Involvement and, if any, the extent of involvement of PCV2 in PRDC was not known so far. It has been surprisingly found that among various pathogens, PCV2 also plays an important role in manifestation, severity and prolongation of clinical signs of PRDC. Thus among others, PCV2 is one of causative agents of PRDC in pigs.
In general, the impact of one causative agent on a multiple-cause disease (i.e., a multi-factorial disease) like PRDC is not predictable. A causative agent may have no effect but may also displace, repress, supersede, overlay or strengthen the effect of the others on the manifestation, severity and prolongation of clinical signs of a multi-factorial disease like PRDC. For example, reduction or elimination of one causative agent of a multi-factorial disease like PRDC may have no effect on the clinical appearance of that disease if at least one further causative agent is present, but it can also significantly reduce the clinical symptoms of that disease, even in the presence of any other causative agent. The higher the number of causative agents that are involved, the lower the expectation that a reduction or elimination of only one causative agent will have a positive influence on the duration of the manifestation, severity or prolongation of the disease, it has been surprisingly found now that manifestation, severity and prolongation of clinical signs of PRDC in pigs can be lessened or reduced by the prophylaxis or treatment, of threatened or affected animals with PCV2 antigen. In particular, the severity and prolongation of clinical signs of or associated with PRDC can strongly be lessened and reduced in pigs infected with PCV2 in combination with pathogens known to cause or be associated with PRDC in pigs, such as PRRSV, Mycoplasma hyopneumoniae, Bordetella bronchiseptica , Swine influenza virus, Mycoplasma hyorhinis and/or Pasteurella multocida . In other words, prophylaxis and treatment of pigs suffering from PRDC with PCV2 antigen has a positive impact on the overall health of the pigs. Furthermore, weight gain during fattening, and mortality in the middle to late phase of fattening of pigs are also positively impacted, which is a great benefit as these factors—overall health, weight gain, mortality—are known to be negatively affected by PRRSV, Mycoplasma hyopneumoniae, Bordetella bronchiseptica , Swine influenza virus, Mycoplasma hyorhinis and/of Pasteurella multocida.
Therefore, according to one aspect, the present invention provides a method for the prophylaxis and treatment of porcine respiratory disease complex (PRDC) and/or any clinical signs associated with PRDC in an animal, comprising the step of administering a therapeutically effective amount of PCV2 antigen or an immunogenic composition comprising a PCV2 antigen to an animal in need of such treatment.
The clinical signs associated with PRDC are selected front the group consisting of cough and dyspnea, slow growth, decreased feed efficiency, lethargy, anorexia, and/or a marked increase in mortality in the middle to late phase of fattening. Thus according to an other aspect, the present invention relates to a method for the prophylaxis and treatment of cough and dyspnea, slow growth, decreased feed efficiency, lethargy, anorexia, and/or a marked increase in mortality associated with PRDC in an animal, comprising the step of administering a therapeutically effective amount of PCV2 antigen or an immunogenic composition comprising a PCV2 antigen to an animal in need of such treatment. Preferably, the cough and dyspnea are refractory to antibiotic therapy.
The term “antigen” as used herein, refers to an amino acid sequence which elicits an immune response in a host. An antigen, as used herein, includes the full-length sequence of any PCV2 proteins, analogs thereof, or immunogenic fragments thereof. The term “immunogenic fragment” refers to a fragment of a protein which, includes one or more epitopes and thus elicits the immune response in a host. Such fragments can be identified using any number of epitope mapping techniques well known in the art. See, e.g. Epitope Mapping Protocols in Methods in Molecular Biology, Vol. 66 (Glenn E. Morris. Ed., 1996) Humana Press, Totowa, N.J. For example, linear epitopes may be determined by e.g., concurrently synthesizing large numbers of peptides on solid supports, the peptides corresponding to portions of the protein molecule, and reacting the peptides with antibodies while the peptides are still attached to the supports. Such techniques are known in the art and described in, e.g. U.S. Pat. No. 4,708,871. Geysen et al. (1984) Proc. Natl. Acad. Sci. USA 81.3998-4002; Geysen et al. (1986) Molec. Immunol 23:709-715. Similarly, conformational epitopes are readily identified by determining spatial conformation of ammo acids such as by, e.g., x-ray crystallography and 2-dimensional nuclear magnetic resonance. See, e.g., Epitope Mapping Protocols, supra.
Synthetic antigens are also included within the definition, for example, poly epitopes, flanking epitopes, and other recombinant or synthetically derived antigens. See, e.g. Bergmann et al. (1993) Eur. J. Immunol. 23:2777-2781; Bergmann et al. (1996), J. Immunol. 157:3242-3249; Suhrbier, A. (1997), Immunol, and Cell Biol. 75:402-408; Gardner et al., (1998) 12th World AIDS Conference, Geneva, Switzerland, Jun. 28-Jul. 3, 1998.
An “immune response” means, but is not limited to, the development in a host of a cellular and/or antibody-mediated immune response to an antigen, an immunogenic composition or vaccine of interest. Usually, an “immune response” includes but is not limited to one or more of the following effects: the production or activation of antibodies, B cells, helper T cells, suppressor T cells, and/or cytotoxic T cells, directed specifically to an antigen or antigens included in the composition or vaccine of interest. Preferably, the host will display either a therapeutic or a protective immunological (memory) response such that resistance to new infection will be enhanced and/or the clinical severity of the disease reduced. Such protection will be demonstrated by either a reduction in number or severity of, or lack of one or more of the symptoms associated with PCV2 infections, in delay of onset of viremia, in a reduced viral persistence, in a reduction of the overall viral load and/or a reduction of viral excretion.
The terms “immunogenic composition” or “vaccine” (both terms are used synonymously) as used herein refers to any pharmaceutical composition containing a PCV2 antigen, which composition can be used to prevent or treat a PCV2 infection-associated disease or condition in a subject. A preferred immunogenic composition can induce, stimulate or enhance the immune response against PCV2. The term thus encompasses both subunit immunogenic compositions, as described below, as well as compositions containing whole killed, or attenuated and/or inactivated PCV2.
Thus according to another aspect, the present invention relates to a method for the prophylaxis and treatment of porcine respiratory disease complex (PRDC) and/or any clinical signs associated with PRDC in an animal, comprising the step of administering an effective amount of PCV2 antigen or an immunogenic composition comprising an PCV2 antigen to that animal in need of such treatment, wherein the immunogenic composition is selected from the group consisting of a subunit immunogenic composition, a composition containing whole killed, or attenuated and/or inactivated PCV2, and combinations thereof.
The term “subunit immunogenic composition” as used herein refers to a composition containing at least one immunogenic polypeptide or antigen, but not all antigens, derived from or homologous to an antigen from PCV2. Such a composition is substantially free of intact PCV2. Thus, a “subunit immunogenic composition” is prepared from at least partially purified or fractionated (preferably substantially purified) immunogenic polypeptides from PCV2, or recombinant analogs thereof. A subunit immunogenic composition can comprise the subunit antigen or antigens of interest substantially free of other antigens or polypeptides from PCV2, or in fractionated from. A preferred immunogenic subunit composition comprises the PCV2 ORF-2 protein as described below. Most preferred are immunogenic subunit compositions, comprising any of the PCV2 antigens provided in WO06/072065, which are all incorporated herein by reference in their entirety.
According to further aspect, the immunogenic composition as used herein most preferably comprises the polypeptide, or a fragment thereof, expressed by ORF-2 of PCV2, PCV2 ORF-2 DNA and protein used herein for the preparation of the compositions and within the processes provided herein is a highly conserved domain, within PCV2 isolates and (hereby, any PCV2 ORF-2 would be effective as the source of the PCV ORF-2 DMA and/or polypeptide as used herein. A preferred PCV2 ORF-2 protein is that of SEQ ID NO: 11 herein and of WO06/072065. A further preferred PCV ORF-2 polypeptide is provided as SEQ ID NO: 5 herein and of WO06/072065. However, it is understood by those of skill in the art that this sequence could vary by as much as 6-10% in sequence homology and still retain the antigenic characteristics that render it useful in immunogenic compositions. The antigenic characteristics of an immunological composition can be, for example, estimated by the challenge experiment, as provided by Example 4 of WO06/072065. Moreover, the antigenic characteristic of a modified antigen is still retained, when the modified antigen confers at least 70%, preferably 80%, more preferably 90% of the protective immunity as compared to the PCV2 ORF-2 protein, encoded by the polynucleotide sequence of SEQ ID NO:3 or SEQ ID NO:4 herein and as provided in WO06/072065.
Thus according to a further aspect, the present invention provides a method for the prophylaxis and treatment of porcine respiratory disease complex (PRDC) and/or any clinical signs associated with PRDC in an animal, comprising the step of administering an effective amount of PCV2 antigen or an immunogenic composition comprising a PCV2 antigen to that animal in need of such treatment, wherein the PCV2 antigen is an antigen of PCV2 ORF-2 protein that has at least 70%, preferably, 80% even more preferably 90% of the protective immunity as compared to compared to the PCV2 ORF-2 protein, encoded by the polynucleotide sequence of SEQ ID NO:3 or SEQ ID NO:4 as provided herein and in WO067072065. Preferably said PCV2 ORF-2 will have the sequence of SEQ ID NO: 11 or SEQ ID NO: 5 herein and of WO06/072065.
In some forms, immunogenic portions of PCV2 ORF-2 protein are used as the antigenic component in the immunogenic composition, comprising PCV2 antigen. The term “immunogenic portion” as used herein refers to truncated and/or substituted forms, or fragments of PCV2 ORF-2 protein and/or polynucleotide, respectively. Preferably, such truncated and/or substituted forms, or fragments will comprise at least 6 contiguous amino acids from the full-length ORF-2 polypeptide. More preferably, the truncated or substituted forms, or fragments will have at least 10, more preferably at least 15, and still more preferably at least 19 contiguous amino acids from the full-length. PCV ORF-2 polypeptide. Two preferred sequences in this respect are provided as SEQ ID NO: 9 and SEQ ID NO:10 herein and of WO06/072065. It is further understood that such sequences may be a part of larger fragments or truncated forms.
As mentioned above, a further preferred PCV2 ORF-2 polypeptide is any one encoded by the nucleotide sequences of SEQ ID NO: 3 or SEQ ID NO: 4. However, it is understood by those of skill in the art that this sequence could vary by as much as 6-20% in sequence homology and still retain the antigenic characteristics that render it useful in immunogenic compositions. In some forms, a truncated or substituted form, or fragment of this PVC2 ORF-2 polypeptide is used as the antigenic component in the composition. Preferably, such truncated or substituted forms, or fragments will comprise at least 18 contiguous nucleotides from the lull-length PCV2 ORF-2 nucleotide sequence, e.g. of SEQ ID NO: 3 or SEQ ID NO: 4. More preferably, the truncated or substituted forms, or fragments, will have at least 30, more preferably as least 45, and still more preferably at least 57 contiguous nucleotides of the full-length PCV2 ORF-2 nucleotide sequence, e.g. SEQ ID NO: 3 or SEQ ID NO: 4.
“Sequence Identity” as it is known in the art refers to a relationship between two or more polypeptide sequences or two or more polynucleotide sequences, namely a reference sequence and a given sequence to be compared with the reference sequence. Sequence identity is determined by comparing the given sequence to the reference sequence after the sequences have been optimally aligned to produce the highest degree of sequence similarity, as determined by the match between strings of such sequences. Upon such alignment, sequence identity is ascertained on a position-by-position basis, e.g., the sequences are “identical” at a particular position, if at that position, the nucleotides or amino acid residues are identical. The total number of such position identities is then divided by the total number of nucleotides or residues in the reference sequence to give % sequence identity. Sequence identity can be readily calculated by known methods, including but not limited to, those described in Computational Molecular Biology, Lesk. A. N., ed. Oxford University Press, New York (1988), Biocomputing: Informatics and Genome Projects. Smith. D. W., ed. Academic Press, New York (1993); Computer Analysis of Sequence Data, Part I, Griffin, A. M., and Griffin, H. G., eds., Humana Press, New Jersey (1994); Sequence Analysis in Molecular Biology, von Heinge, G. Academic Press (1987); Sequence Analysis Primer, Gribskov, M. and Devereux, J., eds., M. Stockton Press, New York (1991); and Carillo, H., and Lipman, D., SIAM J. Applied Math. 48: 1073 (1988), the teachings of which are incorporated herein by reference. Preferred methods to determine the sequence identity are designed to give the largest match between the sequences tested. Methods to determine sequence identity are codified in publicly available computer programs which determine sequence identity between given sequences. Examples of such programs include, but are not limited to, the GCG program package (Devereux, J., et al., Nucleic Acids Research, 12(1):387 (1984)), BLASTP, BLASTN and FASTA (Altschul, S. F. et al., J. Molec. Biol., 215:403-410 (1990). The BLASTX program is publicly available from NCBI and other sources (BLAST Manual, Altschul, S. et al., NCVI NLM NIH Bethesda. MD 20894. Altschul, S. F. et al., J. Molec. Biol., 215:403-410 (1990), the teachings of which are incorporated herein by reference). These programs optimally align sequences using default gap weights in order to produce the highest level of sequence identity between the given and reference sequences. As an illustration, by a polynucleotide having a nucleotide sequence having at least, for example, 85%, preferably 90%, even more preferably 95% “sequence identity” to a reference nucleotide sequence, it is intended that the nucleotide sequence of the given polynucleotide is identical to the reference sequence except that the given polynucleotide sequence may include up to 15, preferably up to 10, even more preferably up to 5 point mutations per each 100 nucleotides of the reference nucleotide sequence. In other words, in a polynucleotide having a nucleotide sequence having at least 85%, preferably 90%, even more preferably 95% identity relative to the reference nucleotide sequence, up to 15%, preferably 10%, even more preferably 3% of the nucleotides in the reference sequence may be deleted or substituted with another nucleotide, or a number of nucleotides up to 15%, preferably 10%, even more preferably 5% of the total nucleotides in the reference sequence may be inserted into the reference sequence. These mutations of the reference sequence may occur at the 5′ or 3′ terminal positions of the reference nucleotide sequence or anywhere between those terminal positions, interspersed either individually among nucleotides in the reference sequence or in one or more contiguous groups within the reference sequence. Analogously, by a polypeptide having a given amino acid sequence having at least, for example, 85%, preferably 90%, even more preferably 95% sequence identity to a reference amino acid sequence, it is intended that the given amino acid sequence of the polypeptide is identical to the reference sequence except that the given polypeptide sequence may include up to 15, preferably up to 10, even more preferably up to 5 amino acid alterations per each 100 amino acids of the reference amino acid sequence. In other words, to obtain a given polypeptide sequence having at least 85%, preferably 90%, even more preferably 95% sequence identity with a reference amino acid sequence, up to 15%, preferably up to 10%, even more preferably up to 5% of the amino acid residues in the reference sequence may be deleted or substituted with another amino acid, or a number of amino acids up to 15%, preferably up to 10%, even more preferably up to 5% of the total number of amino acid residues in the reference sequence may be inserted into the reference sequence. These alterations of the reference sequence may occur at the amino or the carboxy terminal positions of the reference amino acid sequence or anywhere between those terminal positions, interspersed either individually among residues in the reference sequence or in the one or more contiguous groups within the reference sequence. Preferably, residue positions which are not identical differ by conservative amino acid substitutions. However, conservative substitutions are not included as a match when determining sequence identity.
“Sequence homology”, as used herein, refers to a method of determining the relatedness of two sequences. To determine sequence homology, two or more sequences are optimally aligned, and gaps are introduced if necessary. However, in contrast to “sequence identity”, conservative amino acid substitutions are counted as a match when determining sequence homology. In other words, to obtain a polypeptide or polynucleotide having 95% sequence homology with a reference sequence, 85%, preferably 90%, even more preferably 95% of the amino acid residues or nucleotides in the reference sequence must match or comprise a conservative substitution with another amino acid or nucleotide, or a number of amino acids or nucleotides up to 15%, preferably up to 10%, even more preferably up to 5% of the total amino acid residues or nucleotides, not including conservative substitutions, in the reference sequence may be inserted into the reference sequence. Preferably the homolog sequence comprises at least a stretch of 50, even more preferably at least 100, even more preferably at least 250, and even more preferably at least 500 nucleotides.
A “conservative substitution” refers to the substitution of an amino acid residue or nucleotide with another amino acid residue or nucleotide having similar characteristics or properties including size, hydrophobicity, etc., such that the overall functionality does not change significantly.
“Isolated” means altered “by the hand of man” from its natural state, i.e., if it occurs in nature, it has been changed or removed from its original environment, or both. For example, a polynucleotide or polypeptide naturally present in a living organism is not “isolated,” but the same polynucleotide or polypeptide separated from the coexisting materials of its natural state is “isolated”, as the term is employed herein.
Thus, according to a further aspect, the present invention provides a method for the prophylaxis and treatment of porcine respiratory disease complex (PRDC) and/or any clinical signs associated with PRDC in an animal, comprising the step of administering an effective amount of PCV2 antigen or an immunogenic composition comprising a PCV2 antigen to that animal in need of such treatment, wherein said PCV2 ORF-2 protein is any one of those, described above. Preferably, said PCV2 ORF-2 protein is
i) a polypeptide comprising the sequence of SEQ ID NO: 5, SEQ ID NO: 6. SEQ ID NO: 9, SEQ ID NO: 10 or SEQ ID NO: 11 herein and of WO06/07065; ii) any polypeptide that is at least 80% homologous to the polypeptide of i), iii) any immunogenic portion of the polypeptides of i) and/or ii) iv) the immunogenic portion of iii), comprising at least 10 contiguous amino acids included in the sequences of SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 9, SEQ ID NO: 10 or SEQ ID NO: 11 herein and of WO06/072065, v) a polypeptide that is encoded by a DNA comprising the sequence of SEQ ID NO: 3 or SEQ ID NO: 4 herein and of WO06/072065. vi) any polypeptide that is encoded by a polynucleotide that is at least 80% homologous to the polynucleotide of v). vii) any immunogenic portion of the polypeptides encoded by the polynucleotide of v) and/or vi) viii) the immunogenic portion of vii), wherein polynucleotide coding for said immunogenic portion comprises at least 30 contiguous nucleotides included in the sequences of SEQ ID NO: 3, or SEQ ID NO: 4 herein and of WO06/072065.
Preferably any of those immunogenic portions have the immunogenic characteristics of PCV2 ORF-2 protein that is encoded by the sequence of SEQ ID NO: 3 or SEQ ID NO: 4 herein and of WO06/07065.
According to a further aspect PCV2 ORF-2 protein is provided in the immunogenic composition at an antigen inclusion level effective for inducing the desired immune response, namely reducing the incidence of, lessening the seventy of, or preventing or reducing PRDC and/or any clinical symptoms associated with PRDC. Preferably, the PCV2 ORF-2 protein inclusion level is at least 0.2 μg antigen/ml of the final immunogenic composition (μg/ml), more preferably from about 0.2 to about 400 μg/ml, still more preferably from about 0.3 to about 200 μg/ml, even more preferably from about 0.35 to about 100 μg/ml, still more preferably from about 0.4 to about 50 μg/ml, still more preferably from about 0.45 to about 30 μg/ml, still more preferably from about 0.6 to about 15 μg/ml, even more preferably from about 0.75 to about 8 μg/ml, even more preferably from about 1.0 to about 6 μg/ml, still more preferably from about 1.3 to about 3.0 μg/ml, even more preferably from about 1.4 to about 2.5 μg/ml, even more preferably from about 1.5 to about 2.0 μg/ml, and most preferably about 1.6 μg/ml.
According to a further aspect, the PCV ORF-2 antigen inclusion level is at least 0.2 μg/PCV2 ORF-2 protein as described above per dose of the final antigenic composition (μg/dose), more preferably from about 0.2 to about 400 μg/dose, still more preferably from about 0.3 to about 200 μg/dose, even more preferably from about 0.35 to about 100 μg/dose, still more preferably from about 0.4 to about 50 μg/dose, still more preferably from about 0.45 to about 30 μg/dose, still more preferably from about 0.6 to about 15 μg/dose, even more preferably from about 0.73 to about 8 μg/dose, even more preferably from about 1.0 to about 6 μg/dose, still more preferably from about 1.3 to about 3.0 μg/dose, even more preferably from about 1.4 to about 2.5 μg/dose, even more preferably from about 1.5 to about 2.0 μg/dose, and most preferably about 1.6 μg/dose.
The PCV2 ORF-2 polypeptide used in the immunogenic composition in accordance with the present invention can be derived in any fashion including isolation and purification of PCV2 ORF2, standard protein synthesis, and recombinant methodology. Preferred methods for obtaining PCV2 ORF-2 polypeptide are provided in WO06/072065, the teachings and content of which are hereby incorporated by reference in its entirety. Briefly, susceptible cells are infected with a recombinant viral vector containing PCV2 ORF-2 DNA coding sequences, PCV2 ORF-2 polypeptide is expressed by the recombinant virus, and the expressed PCV2 ORF-2 polypeptide is recovered from the supernatant by filtration and inactivated by any conventional method, preferably using binary ethylenimine, which is then neutralized to stop the inactivation process.
The immunogenic composition as used herein also refers to a composition that comprises i) any of the PCV2 ORF-2 proteins described above, preferably in concentrations described above, and ii) at least, a portion, of the viral vector expressing said PCV2 ORF-2 protein, preferably of a recombinant baculovirus. Moreover, the immunogenic composition can comprise i) any of the PCV2 ORF-2 proteins described above, preferably in concentrations described above, ii) at least a portion of the viral vector expressing said PCV2 ORF-2 protein, preferably of a recombinant baculovirus, and iii) a portion of the cell culture supernatant.
Thus, according to a further aspect, the present invention provides a method for the prophylaxis and treatment of porcine respiratory disease complex (PRDC) and/or any clinical signs associated with PRDC in an animal, comprising the step of administering an effective amount of PCV2 antigen or an immunogenic composition comprising an PCV2 antigen to that animal in need of such treatment, wherein the PCV2 antigen is recombinant PCV2 ORF-2, and is preferably a baculovirus expressed PCV2 ORF-2. Preferably those recombinant or baculovirus expressed PCV2 ORF-2s have the sequence as described above.
The immunogenic composition as used herein also refers to a composition that comprises i) any of the PCV2 ORF-2 proteins described above, preferably in concentrations described above, ii) at least a portion of the viral vector expressing said PCV2 ORF-2 protein, preferably of a recombinant baculovirus, and iii) a portion of the cell culture; wherein about 90% of the components have a size smaller than 1 μm.
The immunogenic composition as used herein also refers to a composition that comprises i) any of the PCV2 ORF-2 proteins described above, preferably in concentrations described above, ii) at least a portion of the viral vector expressing said PCV2 ORF-2 protein, iii) a portion of the cell culture, iv) and inactivating agent to inactivate the recombinant viral vector preferably BEI, wherein about 90% of the components i) to iii) have a size smaller than 1 μm. Preferably, BEI is present in concentrations effective to inactivate the baculovirus, preferably in an amount of 2 to about 8 mM BEI, preferably of about 5 mM BEI.
The immunogenic composition as used herein also refers to a composition that comprises i) any of the PCV2 ORF-2 proteins described above, preferably in concentrations described above, ii) at least a portion of the viral vector expressing said PCV2 ORF-2 protein, iii) a portion of the cell culture, iv) an inactivating agent to inactivate the recombinant viral vector preferably BEI, and v) a neutralization agent to stop the inactivation mediated by the inactivating agent, wherein about 90% of the components i) to iii) have a size smaller than 1 μm. Preferably, if the inactivating agent is BEI, said composition comprises sodium thiosulfate in equivalent amounts to BEI.
The polypeptide is incorporated into a composition that can be administered to an animal susceptible to PCV2 infection. In preferred forms, the composition may also include additional components known to those of skill in the art (see also Remington's Pharmaceutical Sciences (1990). 18th ed. Mack Publ., Easton). Additionally, the composition may include one or more veterinary-acceptable carriers. As used herein, “a veterinary-acceptable carrier” includes any and all solvents, dispersion media, coatings, adjuvants, stabilizing agents, diluents, preservatives, antibacterial and antifungal agents, isotonic agents, adsorption delaying agents, and the like. In a preferred embodiment, the immunogenic composition comprises PCV2 ORF-2 protein as provided herewith, preferably in concentrations described above, which is mixed with an adjuvant, preferably Carbopol, and physiological saline.
Those of skill in the art will understand that the composition used herein may incorporate known injectable, physiologically acceptable sterile solutions. For preparing a ready-to-use solutions for parenteral injection or infusion, aqueous isotonic solutions, such as e.g., saline or corresponding plasma protein solutions, are readily available. In addition, the immunogenic and vaccine compositions of the present invention can include diluents, isotonic agents, stabilizers, or adjuvants. Diluents can include water, saline, dextrose, ethanol, glycerol and the like. Isotonic agents can include sodium chloride, dextrose, mannitol, sorbitol, and lactose, among others. Stabilizers include albumin and alkali salts of ethylendiamintetracetic acid, among others.
“Adjuvants” as used herein, can include aluminium hydroxide and aluminium phosphate, saponins e.g., Quil A, QS-21 (Cambridge Biotech Inc. Cambridge Mass.), GPI-0100 (Galenica Pharmaceuticals, Inc., Birmingham, Ala.), water-in-oil emulsion, oil-in-water emulsion, water-in-oil-in-water emulsion. The emulsion can be based in particular on light liquid paraffin oil (European Pharmacopea type); isoprenoid oil such as squalane or squalene oil resulting from theoligomerization of alkenes, in particular of isobutene or decene; esters of acids or of alcohols containing a linear alkyl group, more particularly plant oils, ethyl oleate, propylene glycol di-(caprylate/caprate), glyceryl tri-(caprylate/caprate) or propylene glycol dioleate; esters of branched fatty acids or alcohols, in particular isostearic acid esters. The oil is used in combination with emulsifiers to form the emulsion. The emulsifiers are preferably nonionic surfactants, in particular esters of sorbitan, of mannide (e.g. anhydromannitol oleate), of glycol, of poly glycerol, of propylene glycol and of oleic, isostearic, ricinoleic or hydroxystearic acid, which are optionally ethoxylated, and polyoxypropylene-polyoxyethylene copolymer blocks, in particular the Pluronic products, especially L121. See Hunter et al. The Theory and Practical Application of Adjuvants (Ed. Stewart-Tull, D. E. S.). John Wiley and Sons, NY, pp 51-94 (1995) and Todd et al. Vaccine 15:564-570 (1997).
For example, it is possible to use the SPT emulsion described on page 147 of “Vaccine Design, The Subunit and Adjuvant Approach” edited by M. Powell and M. Newman, Plenum Press, 1995, and the emulsion MF59 described on page 183 of this same book.
A further instance of an adjuvant is a compound chosen from the polymers of acrylic or methacrylic acid and the copolymers of maleic anhydride and alkenyl derivative. Advantageous adjuvant compounds are the polymers of acrylic or methacrylic acid which are cross-linked, especially with polyalkenyl ethers of sugars or poly alcohols. These compounds are known by the term carbomer (Phameuropa Vol. 8, No. 2, June 1996). Persons skilled in the art can also refer to U.S. Pat. No. 2,909,462 which describes such acrylic polymers cross-linked with a polyhydroxylated compound having at least 3 hydroxyl groups, preferably not more than 8, the hydrogen atoms of at least three hydroxyls being replaced by unsaturated aliphatic radicals having at least 2 carbon atoms. The preferred radicals are those containing from 2 to 4 carbon atoms, e.g. vinyls, allyls and other ethylenically unsaturated groups. The unsaturated radicals may themselves contain other substituents, such as methyl. The products sold under the name Carbopol; (BF Goodrich, Ohio. USA) are particularly appropriate. They are cross-linked with an allyl sucrose or with allyl pentaerythritol. Among them, there may be mentioned Carbopol 974P, 934P and 971P. Most preferred is the use of Carbopol, in particular the use of Carbopol 971P, preferably in amounts of about 500 μg to about 5 mg per dose, even more preferred in an amount of about 750 μg to about 2.5 mg per dose and most preferred in an amount of about 1 mg per dose.
Further suitable adjuvants include, but are not limited to, the RIBI adjuvant system (Ribi Inc.), Block co-polymer (CytRx, Atlanta Ga.). SAF-M (Chiron, Emeryville Calif.), monophosphoryl lipid A, Avridine lipid-amine adjuvant, heat-labile enterotoxin from E. coli (recombinant or otherwise), cholera toxin. IMS 1314, or muramyl dipeptide among many others.
Preferably, the adjuvant is added in an amount of about 100 μg to about 10 mg per dose. Even more preferably, the adjuvant is added in an amount of about 100 μg to about 10 mg per dose. Even more preferably, the adjuvant is added in an amount of about 500 μg to about 5 mg per dose. Even more preferably, the adjuvant is added in an amount of about 750 μg to about 2.5 mg per dose. Most preferably, the adjuvant is added in an amount of about 1 mg per dose.
Additionally, the composition can include one or more pharmaceutical-acceptable carriers. As used herein, “a pharmaceutical-acceptable carrier” includes any and all solvents, dispersion media, coatings, stabilizing agents, diluents, preservatives, antibacterial and antifungal agents, isotonic agents, adsorption delaying agents, and the like. Most preferably, the composition provided herewith, contains PCV2 ORF-2 protein recovered from the supernatant of in vitro cultured cells, wherein said cells were infected with a recombinant viral vector containing PCV2 ORF-2 DNA and expressing PCV2 ORF-2 protein, and wherein said cell culture was treated with about 2 to about 8 mM BEI, preferably with about 5 mM BEI to inactivate the viral vector, and an equivalent concentration of a neutralization agent, preferably sodium thiosulfate solution to a final concentration of about 2 so about 8 mM, preferably of about 5 mM.
The present invention also relates to the use of an immunogenic composition for the prophylaxis or treatment of PRDC or the reduction of any clinical signs associated with PRDC that comprises i) any of the PCV2 ORF-2 proteins described above, preferably in concentrations described above, ii) at least a portion of the viral vector expressing said PCV2 ORF-2 protein, iii) a portion of the cell culture, iv) an inactivating agent to inactivate the recombinant viral vector preferably BEI, and v) a neutralization agent to stop she inactivation mediated by the inactivating agent, preferably sodium thiosulfate, in equivalent amounts to BEI; and vi) a suitable adjuvant, preferably Carbopol 971 in amounts described above; wherein about 90% of the components i) to iii) have a size smaller than 1 μm. According to a further aspect, this immunogenic composition further comprises a pharmaceutical acceptable salt, preferably a phosphate salt in physiologically acceptable concentrations. Preferably, the pH of said immunogenic composition is adjusted to a physiological pH, meaning between about 6.5 and 7.5.
The immunogenic composition as used herein also refers to a composition that comprises per one ml i) at least 1.6 μg of PCV2 ORF-2 protein described above, ii) at least a portion of baculovirus expressing said PCV2 ORF-2 protein iii) a portion of the cell culture, iv) about 2 to 8 mM BEI, v) sodium thiosulfate in equivalent amounts to BEI; and vi) about 1 mg Carbopol 971, and vii) phosphate salt in a physiologically acceptable concentration; wherein about 90% of the components i) to iii) have a size smaller than 1 μm and the pH of said immunogenic composition is adjusted to about 6.5 to 7.5.
The immunogenic compositions can further include one or more other immuno-modulatory agents such as, e.g., interleukins, interferons, or other cytokines. The immunogenic compositions can also include Gentamicin and Merthiolate. While the amounts and concentrations of adjuvants and additives useful in the context of the present invention can readily be determined by the skilled artisan, the present invention contemplates compositions comprising from about 50 μg to about 2000 μg of adjuvant and preferably about 250 μg/ml dose of the vaccine composition. Thus, the immunogenic composition as used herein also refers to a composition that comprises from about 1 ug/ml to about 60 μg/ml of antibiotics, and more preferably less than about 30 μg/ml of antibiotics.
The immunogenic composition as used herein also refers to a composition that comprises i) any of the PCV2 ORF-2 proteins described above, preferably in concentrations described above, ii) at least, a portion of the viral vector expressing said PCV2 ORF-2 protein, iii) a portion of the cell culture, iv) an inactivating agent to inactivate the recombinant viral vector preferably BEI, and v) an neutralization agent to stop the inactivation mediated by the inactivating agent, preferably sodium thiosulfate in equivalent amounts to BEI; vi) a suitable adjuvant, preferably Carbopol 971 in amounts described above; vii) a pharmaceutical acceptable concentration of a saline buffer, preferably of a phosphate salt, and viii) an anti-microbiological active agent; wherein about 90% of the components i) to iii) have a size smaller than 1 μm.
The immunogenic composition as used herein also refers to Ingelvac® CircoFLEX™ (Boehringer Ingelheim Vetmedica Inc, St Joseph, Mo., USA), CircoVac® (Merial SAS, Lyon, France), Porcilis PCV (Intervet Inc., Millsboro, Del., USA), or Suvaxyn PCV-2 One Dose® (Fort Dodge Animal Health, Kansas City, Kans., USA). Thus, the present invention also provides a method for the prophylaxis and treatment of porcine respiratory disease complex (PRDC) and/or any clinical signs associated with PRDC in an animal, comprising the step of administering a therapeutically effective amount of PCV2 antigen or an immunogenic composition comprising an PCV2 antigen to an animal in need of such treatment, wherein wherein said immunogenic composition comprising an PCV2 antigen is Ingelvac® CircoFLEX™, CircoVac®, Porcilis PCV and/or Suvaxyn PCV-2 One Dose®, preferably it is Ingelvac® CircoFLEX™.
As described above, PCV2 has been identified to be one relevant causative agent of PRDC. Most of the pigs suffering from PRDC are positive for PCV2 (e.g. Kim et al. Veterinary Journal (2003) 166: 251-256). The treatment of pigs with PCV2 antigen results in the reduction of the respiratory symptoms of PRDC (see Example 3). Thus according to a further aspect, the present invention provides a method for the prophylaxis and treatment of porcine respiratory disease complex (PRDC) and/or any clinical signs associated with PRDC in an animal, comprising the step of administering a therapeutically effective amount of PCV2 antigen or an immunogenic composition comprising a PCV2 antigen to an animal in need of such treatment, wherein the PRDC or the clinical signs associated with PRDC is/are associated with or caused by PCV2. Moreover, the present invention also provides a method for the prophylaxis and treatment of porcine respiratory disease complex (PRDC) and/or any clinical signs associated with PRDC in an animal, comprising the step of administering a therapeutically effective amount of PCV2 antigen or an immunogenic composition comprising an PCV2 antigen to an animal in need of such treatment, wherein the PRDC or the clinical signs associated with PRDC is/are associated with or caused by PCV2 and PRRSV, Actinobacillus pleuropneumoniae, Mycoplasma hyopneumoniae, Bordetella bronchiseptica , Swine influenza virus, Mycoplasma hyorhinis, Streptococcus suis and/or Pasteurella multocida.
As PCV2 is one of the causative agents of PRDC, herds which are positive for PCV2 bear a higher risk of developing PRDC or of developing a more serious duration of PRDC with serious clinical symptoms than PCV2 free herds. The term “herd that is positive for PCV2” as used herein means that at least 1% preferably 10%, more preferably 30%, even more preferably 50%, most preferably 70% of the animals of a herd are infected or become infected to any time with PCV2. This does not necessarily mean, that any animal of the herd develops clinical symptoms known to be caused by PCV2, such as PMWS or PRDC. Thus according to a further aspect, the present invention also provides a method for the prophylaxis and treatment of porcine respiratory disease complex (PRDC) and/or any clinical signs associated with PRDC in an animal, comprising the step of administering a therapeutically effective amount of PCV2 antigen or an immunogenic composition comprising a PCV2 antigen to an animal in need of such treatment, wherein the animal belongs to a herd that is positive for PCV2. Preferably, the PRDC and/or any clinical signs associated with PRDC are caused by PCV2.
As PRDC and the clinical symptoms of PRDC can also be lessened or reduced in the in animals that are co-infected with other causative pathogens of PRDC, the present invention also provides a method for the prophylaxis and treatment of porcine respiratory disease complex (PRDC) and/or any clinical signs associated with PRDC in an animal comprising the step of administering a therapeutically effective amount of PCV2 antigen or an immunogenic composition comprising a PCV2 antigen to an animal in need of such treatment, wherein the animal belongs to a herd that is positive for PCV2 and one or more further pathogen(s) selected from the group consisting of PRRSV, Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Bordetella bronchiseptica , Swine influenza virus, Mycoplasma hyorhinis, Streptococcus suis and/or Pasteurella multocida . Preferably, the PRDC and/or any clinical signs associated with PRDC are caused by PCV2 and at least one other PRDC causing pathogen. The term “a herd that is positive for PCV 2 and one or more further pathogen(s) selected from the group consisting of PRRSV, Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Bordetella bronchiseptica , Swine influenza virus, Mycoplasma hyorhinis, Streptococcus suis and/or Pasteurella multocida ”, as used herein means, that at least 10%, preferably 30%, more preferably 50%, even more preferably 70% of the animals of a heal are infected or become infected at any lane with PCV2 and at least one of the further pathogens listed below. This does not necessarily mean, that any animal of the herd develops clinical symptoms known to be caused by PCV2 and at least one of the pathogens listed above, e.g. PRDC. Preferably, the PRDC and/or any clinical signs associated with PRDC are caused at least by PCV2.
PRDC does not only affect a defined number of animals, it normally affects all animals of herd (the whole herd). In other words, if at least one animal of a farm develops PRDC, the causative agents of PRDC are persistently present within the live stock of that farm. Thus according to a further aspect, the present invention also provides a method for the prophylaxis and treatment of porcine respiratory disease complex (PRDC) and/or any clinical signs associated with PRDC in an animal, comprising the step of administering a therapeutically effective amount of PCV2 antigen or an immunogenic composition comprising a PCV2 antigen to an animal in need of such treatment, wherein the animal belongs to a herd that is positive for PCV2. Preferably, the PRDC and/or any clinical signs associated with PRDC are caused by PCV2. The term “a herd that is positive for PCV2” as used herein means that at least 1% preferably 10%, more preferably 30%, even more preferably 50%, and most preferably 70% of the animals of a herd are infected or become infected to at any time with PCV2. This does not necessarily mean, that any animal of the farm develops clinical signs known to be caused by PCV2, such as PMWS or PRDC. Preferably, the PRDC and/or any clinical signs associated with PRDC are caused by PCV2.
As PRDC and the clinical symptoms of PRDC can also be lessened or reduced in animals that are co-infected with other causative pathogens of PRDC, the present invention also provides a method for the prophylaxis and treatment of porcine respiratory disease complex (PRDC) and/or any clinical signs associated with PRDC in an animal, comprising the step of administering a therapeutically effective amount of PCV2 antigen or an immunogenic composition comprising a PCV2 antigen to an animal in need of such treatment, wherein the animal belonging to a farm that is positive for PCV2 and one or more further pathogen(s) are selected from the group consisting of PRRSV, Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Bordetella bronchiseptica , Simian influenza virus, Mycoplasma hyorhinis, Streptococcus suis and/or Pasteurella multocida . Preferably, the PRDC and/or any clinical signs associated with PRDC are caused by PCV2 and at least one other PRDC causing pathogen. The term “a herd that is positive for PCV2 and one or more further pathogen(s) selected from the group consisting of PRRSV, Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Bordetella bronchiseptica . Swine influenza virus, Mycoplasma hyorhinis and/or Pasteurella multocida ”, as used herein means, that at least 10%, preferably 30%, more preferably 50%, even more preferably 70% of the animals of a herd are infected or become infected to at any time with PCV2 and at least one of the further pathogens listed below. This does not necessarily mean, that any animal of the herd develops clinical symptoms known to be caused by PCV2 and at least one of the pathogens listed above, e.g. PRDC.
Maternally derived immunity has been shown to confer a certain degree of protection against PCV2 infection and clinical diseases associated with PCV2 infections. This protection has been shown to be titer dependent: higher titers are generally protective whereas lower titers are not (McKeown et al., 2005; Clin. Diagn. Lab. Immunol; 12: 1347-1351). The mean antibody half-life in weanlings has been estimated to be 19.0 days and the window for PCV2-passive antibody decay within a population is relatively wide (Opriessnig et al. 2004, J. Swine Health Prod, 12:186-191). The presence of maternally derived antibodies not only may confer a certain degree of protection against viral infections, which however is not predictable, but may also be known to impair the efficacy of immunization. It has surprisingly been found, that the presence of anti-PCV2 antibodies, in particular of anti-PCV2 antibody titers of up to 1:20480, does not affect the efficacy of the PCV2 treatment. Thus according to a further aspect, the present invention provides a method for the prophylaxis and treatment of porcine respiratory disease complex (PRDC) and/or any clinical signs associated with PRDC in at) animal, comprising the step of administering a therapeutically effective amount of PCV2 antigen or an immunogenic composition comprising a PCV2 antigen to an animal in need of such treatment having anti-PCV2 antibodies, preferably wherein said animal has a detectable anti-PCV2 antibody titer of up to 1:100, preferably of more than 1:100, even more preferably of more than 1:250, even more preferably of more than 1:500, even more preferably of 1:640; even more preferably of more than 1:750, most preferably of more than 1:1000. Preferably, those anti-PCV2 antibody titers are detectable and quantifiable in a specific anti-PCV2 immune assay, preferably in the assay as described in Example 2.
Methods for the detection and quantification of anti-PCV2 antibodies are well known in the art. For example detection and quantification of PCV2 antibodies can be performed by indirect immunofluorescence as described in Magar et al., 2000, Can. J. Vet Res.; 64: 184-186 or Magar et al., 2000, J. Comp. Pathol; 123: 258-269. Further assays for quantification of anti-PCV2 antibodies are described in Opriessnig et al. 2006, 37 th Annual Meeting of the American Association of Swine Veterinarians. Moreover. Example 2 also describes an indirect immunofluorescence assay, that can be used by a person skilled in the art. In cases of controversial results and in any question of doubt, anti-PCV2 titers as mentioned herein, refer to those which are/can be estimated by the assay as described in Example 2.
According to a further, more general aspect, the present invention provides a method for the prophylaxis of PRDC, preferably associated with or caused by PCV2, or for reduction of clinical symptoms caused by or associated with PRDC in young animals, comprising the step of administering an effective amount of a PCV2 antigen to that young animal in need of such treatment.
The term “young animal” as used herein refers to an animal of 1 to 22 days of age. Preferably, by the term young animal, an animal of 1 to 20 days of age is meant. More preferably, the term young animal refers to an animal of 1 to 15 days of age, even more preferably of 1 day of age to 14 days of age, even more preferably of 1 to 12 days of age, even more preferably of 1 to 10 days of age, even more preferably of 1 to 8 days of age, even more preferably of 1 to 7 days of age, even more preferably of 1 to 6 days of age, even more preferably of 1 to 5 days of age, even more preferably of 1 to 4 days of age, even more preferably of 1 to 3 days of age, even more preferably of 1 or 2 day(s) of age, most preferably to an animal of 1 day of age. Thus according to a further aspect, the present invention provides a method for the prophylaxis of PRDC, preferably associated with or caused by PCV2, or for reduction of clinical symptoms caused by or associated with PRDC in young animals, comprising the step of administering an effective amount of a PCV2 antigen to an animal of 1 to 22 days of age, preferably of 1 to 20 days of age, more preferably of 1 to 15 days of age, even more preferably of 1 to 14 days of age, even more preferably of 1 to 12 days of age, even more preferably of 1 to 10 days of age, even more preferably of 1 to 8 days of age, even more preferably of 1 to 7 days of age, even more preferably of 1 to 6 days of age, even more preferably of 1 to 5 days of age, even more preferably of 1 to 4 days of age, even more preferably of 1 to 3 days of age, even more preferably of 1 or 2 day(s) of age, most preferably at 1 day of age in need of such treatment. For example evidence is given that vaccination/treatment on 19 to 22 days of age shows or provides high efficacy of vaccination. Moreover, vaccination/treatment at days 12 to 18 of age has also be shown to be very effective in reducing clinical symptoms associated with or caused by PRDC, reduction of overall viral load, reduction of duration of viremia, delay in onset of viremia, and weight gain.
Due to the ubiquity of PCV2 in the field, most of the young piglets are seropositive in respect to PCV2. Thus according so a further aspect, the present invention provides a method for the prophylaxis of PRDC, preferably associated with or caused by PCV2, or for the reduction of clinical symptoms caused by or associated with PRDC in young annuals having anti-PCV2 antibodies, preferably at the day of vaccination, comprising the step of administering an effective amount of a PCV2 antigen to an animal of 1 to 22 days of age, preferably of 1 to 20 days of age, more preferably of 1 to 15 days of age, even more preferably of 1 to 14 days of age, even more preferably of 1 to 12 days of age, even more preferably of 1 to 10 days of age, even more preferably of 1 to 8 days of age, even more preferably of 1 to 7 days of age, even more preferably of 1 to 6 days of age, even more preferably of 1 to 5 days of age, even more preferably of 1 to 4 days of age, even more preferably of 1 to 3 days of age, even more preferably at 1 or 2 day(s) of age, most preferably at 1 day of age in need of such treatment. Preferably, said young animals, at the day of vaccination/treatment, have a detectable anti-PCV2 antibody titer of up to 1:100, preferably of more than 1:100, even more preferably of more than 1:250, even more preferably of more than 1:500, even more preferably of more than 1:640, even more preferably of more than 1:750, and most preferably of more than 1:1000 at the day of vaccination/treatment.
As described above, vaccination/treatment of animals suffering from PRDC with PCV2 antigen resulted in a shortening of viremic phase as compared to non vaccinated control animals. The average shortening time was 15.4 days as compared to non vaccinated control animals of the same species. Therefore, according to a further aspect, the present invention also provides a method for the treatment or prophylaxis of PRDC, preferably associated with or caused by PCV2, or for reduction of clinical symptoms caused by or associated with PRDC in animals, comprising the step of administering an effective amount of a PCV2 antigen to that animal in need of such treatment, wherein the treatment or prophylaxis results in shortening of the viremia phase of 5 or more days, preferably 6 or more days, even more preferably of 7 or more days, even more preferably of 8 or more days, even more preferably of 9, even more preferably of 10, even more preferably of 12, even more preferably of 14, most preferably of more than 15 days as compared to animals of a non-treated control group of the same species.
In general, the vaccination of pigs suffering from PRDC resulted in a reduction in the loss of weight gain, reduction in clinical respiratory signs such, as cough and dyspnea, a shorter duration of viremia, an earlier end to viremia, and a lower virus load. Therefore, according to a further aspect, the present invention provides a method for the treatment or prophylaxis of PRDC, preferably associated with or caused by PCV2, or for reduction of clinical symptoms associated with or caused by PRDC in animals, comprising the step of administering an effective amount of PCV2 antigen to an animal in need of such treatment, wherein said treatment or prophylaxis results in an improvement in comparison to animals of a non-treated control group of the same species in a vaccine efficacy parameter selected from the group consisting of a reduction in the loss of weight gain, reduction in clinical respiratory signs such as cough and dyspnea, a shorter duration of viremia, an earlier end to viremia, a lower virus load, or combinations thereof.
The term “an effective amount” as used herein means but is not limited to an amount of antigen, that elicits or is able to elicit an immune response in an animal, to which said effective dose of PCV2 antigen is administered.
The amount that is effective depends on the ingredients of the vaccine and the schedule of administration. Typically, when an inactivated virus or a modified live virus preparation is used in the combination vaccine, an amount of the vaccine containing about 10 2.0 to about 10 9.0 TCID 50 per dose, preferably about 10 3.0 to about 10 8.0 TCID 50 per dose, more preferably, about 10 4.0 to about 10 8.0 TCID 50 per dose. In particular, when modified live PCV2 is used in the vaccines, the recommended dose to be administered to the susceptible animal is preferably about 10 3.0 TCID 50 (tissue culture infective dose 50% end point)/dose to about 10 6.0 TCID 50 /dose and more preferably about 10 4.0 TCID 50 /dose to about 10 5.0 TCID 50 /dose. In general, the quantity of antigen will be between 0.2 and 5000 micrograms, and between 10 2.0 and 10 9.0 TCID 50 , preferably between 10 3.0 and 10 6.0 TCID 50 , more preferably between 10 4.0 and 10 5.0 TCID 50 , when purified antigen is used.
Sub-unit vaccines are normally administered with an antigen inclusion level of at least 0.2 μg antigen per dose, preferably with about 0.2 to about 400 μg/dose, still more preferably with about 0.3 to about 200 μg/dose, even more preferably with about 0.35 to about 100 μg/dose, still more preferably with about 0.4 to about 50 μg/dose, still more preferably with about 0.45 to about 30 μg/dose, still more preferably with about 0.6 to about 16 μg/dose, even more preferably with about 0.75 to about 8 μg/dose, even more preferably with about 1.0 to about 6 μg/dose, still more preferably with about 1.3 to about 3.0 μg/dose.
Unexpectedly, it was found that the prophylactic use of the immunogenic compositions described supra, is affective for the reduction of clinical symptoms caused by or associated with PRDC, preferably caused at least by PCV2 in animals. Moreover, the antigenic composition described herein reduces the overall circovirus load including a later onset, a shorter duration, an earlier end of viremia, and a reduced viral load and its immunosuppressive impact in animals suffering from PRDC, and thereby resulting in a higher level of general disease resistance and a reduced incidence of PRDC.
The composition according to the invention may be applied intradermally, intratracheally, or intravaginally. The composition preferably may be applied intramuscularly or intranasally, most preferably intramuscularly. In an animal body, it can prove advantageous to apply the pharmaceutical compositions as described above via an intravenous or by direct injection into target tissues. For systemic application, the intravenous, intravascular, intramuscular, intranasal, intraarterial, intraperitoneal oral, or intrathecal routes are preferred. A more local application can be effected subcutaneously, intradermally, intracutaneously, intracardially, intralobally, intramedullary, intrapulmonarily or directly in or near the tissue to be treated (connective-, bone-, muscle-, nerve-, epithelial tissue). Depending on the desired duration and effectiveness of the treatment, the compositions according to the invention may be administered once or several times, also intermittently, for instance on a daily basis for several days, weeks or months and in different dosages.
Preferably, at least one dose of the immunogenic composition as described above is intramuscularly administered to the subject in need thereof. According to a further aspect, the PCV2 antigen or the immunogenic composition comprising any such PCV2 antigen as described herein is bottled in and administered at one (1) mL per dose. Thus, according to a fusilier aspect, the present invention also provides a 1 ml immunogenic composition, comprising PCV-2 antigen as described herein, for the treatment or prophylaxis of porcine respiratory disease complex (PRDC) and/or any clinical signs associated with PRDC, preferably caused by PCV2, in animals, comprising the step of administering an effective amount of a PCV2 antigen to that animal in need of such treatment.
According to a further aspect, at least one further administration of at least one dose of the immunogenic composition as described above is given to a subject in need thereof, wherein the second or any further administration is given at least 14 days beyond the initial or any former administrations. Preferably, the immunogenic composition is administered with an immune stimulant. Preferably, said immune stimulant is given at least twice. Preferably, at least 3 days, more preferably at least 5 days, even more preferably at least 7 days are in between the first and the second or any further administration of the immune stimulant. Preferably, the immune stimulant is given at least 10 days, preferably 15 days, even more preferably 20, even more preferably at least 2.2 days beyond the Initial administration of the immunogenic composition provided herein. A preferred immune stimulant is, for example, keyhole limpet hemocyanin (KLH), preferably emulsified with incomplete Freund's adjuvant (KLH/ICFA). However, it is herewith understood, that any other immune stimulant known to a person skilled in the art can also be used. The term “immune stimulant” as used herein, means any agent or composition that can trigger the immune response, preferably without initiating or increasing a specific immune response, for example the immune response against a specific pathogen. It is further instructed to administer the immune stimulant in a suitable dose.
The present invention also relates to the use of a PCV2 antigen or an immunogenic composition comprising PCV2 antigen for the preparation of a medicine for the prophylaxis and treatment of porcine respiratory disease complex (PRDC) and/or any clinical sign associated with PRDC in an animal. Preferably, the PRDC or the clinical signs associated with PRDC are caused at least PCV2, more preferably in combination with one or more further pathogens selected from the group consisting of PRRSV, Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Bordetella bronchiseptica , Simian influenza virus, Mycoplasma hyorhinis, Streptococcus suis and/or Pasteurella multocida . More preferably, the PCV2 antigen is a recombinant antigen, preferably PCV2 ORF-2, even more preferably Ingelvac® CircoFLEX™.
The “animal” as used herein means a swine, pig or piglet. Thus, according to a further aspect, the present invention provides a method for the prophylaxis and treatment of porcine respiratory disease complex (PRDC) and/or any clinical signs associated with PRDC in a pig, comprising the step of administering a therapeutically effective amount of PCV2 antigen or an immunogenic composition comprising an PCV2 antigen to an animal in need of such treatment. Preferably, the PRDC is caused at least by PCV2, preferably in combination with at least one further aetiologic agent known to cause PRDC, e.g. PRRSV, Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Bordetella bronchiseptica , Swine influenza virus, Mycoplasma hyorhinis, Streptococcus suis and/or Pasteurella multocida . Preferably, the PCV2 antigen or immunogenic composition comprising PCV 2 antigen is anyone of those described supra, most preferably the PCV2 antigen is Ingelvac® CircoFLEX™.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The following examples set forth preferred materials and procedures in accordance with the present invention. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods, devices, and materials are now described. It is to be understood, however, that these examples are provided by way of illustration only, and nothing therein should be deemed a limitation upon the overall scope of the invention.
Example 1
Preparation of PCV2 ORF-2 Antigen
Initial SF+ cell cultures from liquid nitrogen storage were grown in Excell 420 media (JRH Biosciences, Inc., Lenexa, Kans.) in suspension in sterile spinner flasks with constant agitation. The cultures were grown in 100 mL to 250 mL spinner flasks with 25 to 150 mL of Excell 420 serum-free media. When, the cells had multiplied to a cell density of 1.0-8.0×10 6 cells/mL, they were split to new vessels with a planting density of 0.5-1.5×10 6 cells/mL. Subsequent expansion cultures were grown in spinner flasks up to 36 liters in size or in stainless steel bioreactors of up to 300 liters for a period of 2-7 days at 25-29° C.
After seeding, the flasks were incubated at 27° C. for four hours. Subsequently, each flask was seeded with a recombinant baculovirus containing the PCV2 ORF-2 gene (SEQ ID NO: 4). The recombinant baculovirus containing the PCV2 ORF-2 gene was generated as described in WO06/072065. After being seeded with the baculovirus, the flasks were then, incubated at 27±2° C. for 7 days and were also agitated at 100 rpm during that time. The flasks used ventilated caps to allow for air flow.
After incubation, the resulting supernatant were harvested, filtered in order to remove cell debris, and inactivated. The supernatant was inactivated by bringing its temperature to 37±2° C. and binary ethylenimine (BEI) was added to the supernatant to a final concentration of 5 mM. The samples were then stirred continuously far 72 to 96 hrs. A 1.0 M sodium thiosulfate solution to give a final minimum concentration of 5 mM was added to neutralize any residual BEI. After inactivation, PCV2 ORF-2 buffered with phosphate buffer and Carbopol was added to about 0.5 to 2.5 mg/dose. The final dose comprises about 16 μg PCV2 ORF-2 antigen.
Example 2
Anti PCV-2 Immuno Assay
PK15 (e.g. ATCC CCL-33) or VIDO R1 cells described in WO 02/07721, are seeded onto a 96 well plate (about 20,000 to 60,000 cells per wells). Cells are infected with a PCV2 isolate, when monolayers are approximately 65 to 85% confluent. Infected cells are incubated for 48 hours. Medium is removed and wells are washed 2 times with PBS. The wash buffer is discarded and cells are treated with cold 50/50 methanol/acetone fixative (˜100 μl/well) for about 15 min at about −20° C. The fixative is discarded and the plates are air dried. Serial dilutions of porcine serum samples are prepared in PBS, added to the plates and incubated to allow antibodies to bind if present in the serum samples for about 1 hr at 36.5±1° C. In addition, serial dilutions of an anti-PCV2 positive and negative control sample (Positive Control and Negative Control Samples) are run in parallel. The plates are then washed three times with PBS. The PBS is discarded. Plates are then stained with a commercial Goat anti-Swine FITC conjugate diluted 1:100 in PBS and incubated for about 3 hr at 36.5±1° C., which allows detection of antibodies bound to infected cells. After incubation is complete, the microplates are removed from incubator, the conjugate is discarded and the plates are washed 2 times with PBS. The plates are read using UV microscopy and individual wells reported as positive or negative. The Positive Control and Negative Control samples are used to monitor the test system. If the controls are within expected ranges the test results are acceptable in regard to test method parameters. The serum antibody liters are calculated using the highest dilution showing specific IFA reactivity and the number of wells positive per dilution, or a 50% endpoint is calculated using the appropriate Reed-Muench formula.
Example 3
Efficacy of PCV2 ORF-2 (Ingelvac® CircoFLEX™) in Treatment of PRDC
Objective
The purpose of this study was the demonstration of the efficacy of Ingelvac® CircoFLEX in the control of PCV2-associated PRDC.
Study Performance
1542 conventional pigs belonging to three consecutive week groups, each comprising approximately 500 animals, were included into the study. The study animals were blocked by weight and litter assignment and randomly assigned to one group of vaccinates (n=769) and one control group (n=773).
Group 1: At study day 0 the pigs were vaccinated intramusculary at the age of approximately 20 days by a single dose of Ingelvac® CircoFLEX containing PCV2 ORF-2 protein as the active substance with an RP of 1 (per dose of 1 ml) and Carbopol® as adjuvant. Group 2: The control group received 1 ml of control article which contained PCV2 ORF-2 protein free cell culture supernatant and Carbopol® as adjuvant. Group 3; Untreated pigs.
The study was terminated at the end of fattening (study week 22).
Parameters Recorded
Parameters recorded were as follows:
Individual body weight (all animals) Frequency of ‘runts’ (all animals) Clinical signs (all animals) Mortality (all animals) PCV2 viremia in serum: onset, end, duration of viremia, virus load (17% of study animals) Necropsy (every dead or euthanized animal, if possible)
Disease Situation at the Farm
According to the disease history of the rearing and fattening farm, animals experienced respiratory symptoms related to the Porcine Respiratory Disease Complex (PRDC) from the middle of fattening onwards. These symptoms were accompanied by a reduced weight gain (ADWG 750-780 g) and an increased mortality fate (5.5-6.6%) during the fattening period. Pathogens that were considered to be involved in PRDC at that time were PCV2, PRRSV, Pasteurella multocida, Bordetella bronchiseptica and occasionally SIV. For the course of this study Mycoplasma hyopneumoniae and Mycoplasma hyorhinis were additionally found to be involved in this disease complex. Interestingly, results from this study give evidence for the fact that both the PRRSV and the Mycoplasma hyopneumoniae infection occurred approximately 4-6 weeks before onset of PCV2 viremia. However, as the number of dead animals over the course of the study and the frequency of respiratory symptoms before and after the onset of PCV2 viremia reveal, animals remained rather unaffected from these two infections pathogens.
Results
Body Weight, Weight Gain, Average Daily Weight Gain
Body weight of the two treatment groups was comparable at the time of study initiation. At study weeks 17 and 22, the body weight of the vaccinated group was significantly higher than the body weight of the placebo-treated group (p=0.0007 and p<0.0001, respectively).
From study initiation until study week 22, vaccinated animals had gained 2.8 kg more weight than placebo-treated animals. This corresponds to a 13 g/d higher ADWG in vaccinated animals from study initiation until study week 17 and an 18 g/d higher ADWG in vaccinated animals until study week 22. For the entire fattening period (study week 7-22), the ADWG could thus be increased from 777 g/d in placebo-treated animals (comparable to historical. 750-780 g/d ADWG) to 803 g/d in vaccinated animals (Table 1 and FIG. 1 ).
TABLE 1 Comparison of Body weight, Weight gain and ADWG (pooled data of all three week groups) Placebo- treated Vaccinated Study Group Group Difference week (LSMean) (LSMean) (IVP-CP) p-value 1) Live 0 6.45 kg 6.59 kg 0.14 kg 0.1289 ns Body 7 25.79 kg 26.18 kg 0.39 kg 0.3955 ns Weight 12 50.63 kg 51.01 kg 0.38 kg 0.9564 ns 17 78.29 kg 80.22 kg 1.93 kg 0.0007 *** 22 106.55 kg 109.77 kg 3.22 kg <0.0001 *** Weight 0-17 71.97 kg 73.51 kg 1.54 kg 0.0007 *** Gain 0-22 100.22 kg 103.02 kg 2.80 kg <0.0001 *** ADWG 0-17 603 g/d 616 g/d 13 g/d 0.0007 *** 0-22 649 g/d 667 g/d 18 g/d <0.0001 *** 7-22 777 g/d 803 g/d 26 g/d <0.0001 *** 1) p-value of t-test for comparison between groups, ns: not significant, *** significant, p ≦ 0.001
Viremia in Blood
Vaccinated animals showed a slightly later onset of viremia (1.5 days later), a significantly earlier end of viremia (p<0.0001), a significantly shorter duration of viremia (p<0.0001), a significantly lower number of positive sampling days per animal (p<0.0001) and a significant general reduction in the virus load (p<0.0001). The highest proportion of viremic animals was observed at study week 17 with 75% viremic animals in the placebo group and 28% viremic animals in the vaccinated group.
TABLE 2 Comparison of Viremia in Blood (pooled data of all three week groups) Placebo- treated Vaccinated Group Group Difference Study week (Mean) (Mean) (CP-IVP) p-value 2) Onset of viremia 104.4 days 105.9 days −1.5 days 0.3244 ns End of viremia 138.7 days 123.3 days 15.4 days <0.0001*** Duration of 34.3 days 17.4 days 16.9 days <0.0001*** viremia Number of 4.3 days 1.4 days 2.9 days <0.0001*** positive sampling days Mean Sum gE 1) 22.7 7.1 15.6 <0.0001*** (log 10) 1) gE: genomic equivalents per ml 2) p-value (of the Wilcoxon Mann-whitney test for comparison between groups), ns: not significant. ***significant, p ≦ 0.001
Correlation of Viremia in Blood with Body Weight
FIG. 2 illustrates the virus load in sample animals of both treatment groups over the course of the study compared to the difference in live body weight (CP-IVP) of all animals from both treatment groups on the respective weighing time points. When comparing the curves for body weight difference with the bars representing the virus load, it becomes obvious that the observed differences in body weight between both, treatment groups (study weeks 17 and 22) occur after the onset of viremia (study week 14-46). While the virus load is decreasing after a peak at study week 17, the difference in body weight between groups is further increasing until the end of fattening. Together these data give evidence for a correlation between the observed higher body weight gain development at study weeks 17 and 22 in the vaccinated group and the onset, duration and level of viremia.
Calculation of the Spearman rank coefficient confirmed the existence of a statistical significant correlation between viremia and the difference in weight gain development in placebo-treated animals at study weeks 17 and 22. A low body weight in placebo-treated animals was correlated with an early onset, a long duration of viremia and a high virus load. For vaccinated animals no such correlation could be found indicating that the higher body weight in the vaccinated animals was the result of a delayed onset and shorter duration of viremia as well as of a lower virus load in blood.
Frequency of Runts
No significant differences in the frequency of ‘runts’ could be observed between the vaccinated and the placebo-treated group on any of the respective weighing time points. After the onset of PCV2 viremia (study week 14-16), the frequency of ‘runts’ was generally low in both treatment groups (2.2-3.9%).
TABLE 3 Comparison of the frequency of ‘runts’ (pooled data of all three week groups) Before After Onset of viremia onset of viremia Study Week 0 7 12 17 22 CP 17.08% 11.16% 5.02% 3.57% 2.97% IVP 17.17% 11.03% 5.32% 3.99% 2.23% P 1.0000 0.6845 0.8147 0.6830 0.4082 P: p-value of t-test for comparison between groups; p > 0.05 no significant
Clinical Signs
Before onset of viremia predominant clinical signs were lamenesses, cough and diarrhea (in 8-12% of animals). They occurred with equal frequency in both treatment groups. Upon necropsy of dead animals and subsequent microbiological examination Streptococcus suis was identified as a possible infectious pathogen for lamenesses, Haemophilus parasuis and Bordetella bronchiseptica were identified as possible infectious pathogens for cough, and haemolytic E. coli was identified as a possible reason for diarrhea.
After the onset of viremia, the predominant clinical symptoms observed in animals of both treatment groups were cough and lamenesses. Serological periodic analyses for other infectious pathogens and microbiological findings upon necropsy revealed that PCV2 viremia was accompanied by a (preceding) PRRSV and Mycoplasma hyopneumoniae infection. Together with PCV2, these infectious pathogens form part of PRDC which is considered to be the cause for the increased frequency of coughing animals after the onset of viremia. Compared to the placebo-treated animals, the frequency of cough and dyspnea in vaccinated animals was reduced by 12.2% and 17.5%, respectively. These findings are however without any statistical significance. The increased frequency of lamenesses after the onset of viremia compared to the time before onset of viremia is most likely caused by chronic forms of Streptococcus suis , arthritis, or by weaknesses of the joint apparatus and these affected both treatment groups in the same way (p= 0.8323). Similarly, the frequency of other clinical findings (diarrhea, skin abnormalities, behaviour) after the onset of viremia was almost equal between the two treatment groups.
Mortality
Before onset of viremia the mortality rate was comparable in both treatment groups (vaccinated animals: 5.20%, placebo-treated animals: 5.17%). After the onset of viremia placebo-treated animals had a significant higher mortality rate than vaccinated animals (vaccinated animals: 1.51%, placebo-treated animals: 3.68%, p=0.0127). Compared to placebo-treated animals, the mortality rate in vaccinated animals was reduced by 59%.
CONCLUSION
The study has been conducted on a farm that showed typical symptoms of PRDC at the late phase of fattening. At the age of 17 to 19 weeks, pigs developed respiratory symptoms, an increased mortality rate, and a loss of weight gain. Upon serological and microbiological screening PCV2, PRRSV, Mycoplasma hyopneumoniae, Mycoplasma hyorhinis and Pasteurella multocida were identified as possible pathogens being involved in this disease complex.
Compared to the placebo-treated control group the following statistically significant findings were noted for the vaccinated group:
reduction of loss of weight gain reduction of mortality reduction of the duration of viremia and earlier end of viremia reduction of the virus load reduction of cough and dyspnea
As expected, no statistically significant differences could be observed with regard to the frequency of ‘runts’ since the occurrence of ‘runts’ is not a typical finding for PRDC.
Together these findings allow the following conclusions:
1. The study has been conducted in a herd that got affected with PRDC at the middle to late phase of fattening. PCV2 was clearly involved in this disease complex since respiratory symptoms, loss of weight gain and an increase in mortality was only observed after the onset of viremia. 2. Vaccination of animals with Ingelvac® CircoFLEX™ could reduce or even prevent clinically relevant parameters that are related to PCV2 associated PRDC. | The present invention relates to the use of an immunogenic composition comprising a porcine circovirus type 2 (PCV2) antigen for the prevention and treatment, including a reduction in the severity of, duration of, and manifestations of, porcine respiratory disease complex (PRDC) in animals, preferably in pigs. | 0 |
This is a continuation of application Ser. No. 07/810,908, filed Dec. 20, 1991, which is a divisional of application Ser. No. 07/752,368, filed Sep. 3, 1991, now abandoned, which is a divisional of application Ser. No. 07/013,477, filed Feb. 11, 1987, (now U.S. Pat. No. 5,079,342), which is a CIP of application Ser. No. 07/003,764, filed Jan. 16, 1987, (now U.S. Pat. No. 5,051,496), which is a CIP of application Ser. No. 06/933,184, filed Nov. 21, 1986, now abandoned, which is a CIP of application Ser. No. 06/916,080, filed Oct. 6, 1986, now abandoned, which is a CIP of application Ser. No. 06/835,228, filed Mar. 3, 1986, now U.S. Pat. No. 4,839,288.
BACKGROUND OF THE INVENTION
The disclosures of each of these predecessor applications are expressly incorporated herein by reference.
The invention relates to cloned DNA sequences analogous to the genomic RNA of a virus known as Lymphadenopathy-Associated Virus II ("LAV-II"), a process for the preparation of these cloned DNA sequences, and their use as probes in diagnostic kits. In one embodiment, the invention relates to a cloned DNA sequence analogous to the entire genomic RNA of HIV-2 and its use as a probe. The invention also relates to polypeptides with amino acid sequences encoded by these cloned DNA sequences and the use of these polypeptides in diagnostic kits.
According to recently adopted nomenclature, as reported in Nature, May 1986, a substantially-identical group of retroviruses which has been identified as one causative agent of AIDS are now referred to as Human Immunodeficiency viruses I (HIV-1). This previously-described group of retroviruses includes Lymphadenopathy-Associated Virus I (LAV-I), Human T-cell Lymphotropic Virus-III (HTLV-III), and AIDS-Related Virus (ARV).
Lymphadenopathy-Associated Virus II has been described in U.S. application Ser. No. 835,228, which was filed Mar. 3, 1986, and is specifically incorporated herein by reference. Because LAV-II is a second, distinct causative agent of AIDS, LAV-II properly is classifiable as a Human Immunodeficiency Virus II (HIV-2). Therefore, "LAV-II" as used hereinafter describes a particular genus of HIV-2 isolates.
While HIV-2 is related to HIV-1 by its morphology, its tropism and its in vitro cytopathic effect on CD4 (T4) positive cell lines and lymphocytes, HIV-2 differs from previously described human retroviruses known to be responsible for AIDS. Moreover, the proteins of HIV-1 and 2 have different sizes and their serological cross-reactivity is restricted mostly to the major core protein, as the envelope glycoproteins of HIV-2 are not immune precipitated by HIV-1-positive sera except in some cases where very faint cross-reactivity can be detected. Since a significant proportion of the HIV infected patients lack antibodies to the major core protein of their infecting virus, it is important to include antigens to both HIV-1 and HIV-2 in an effective serum test for the diagnosis of the infection by these viruses.
HIV-2 was first discovered in the course of serological research on patients native to Guinea-Bissau who exhibited clinical and immunological symptoms of AIDS and from whom sero-negative or weakly sero-positive reactions to tests using an HIV-1 lysate were obtained. Further clinical studies on these patients isolated viruses which were subsequently named "LAV-II."
One LAV-II isolate, subsequently referred to as LAV-II MIR, was deposited at the Collection Nationale des Cultures de Micro-Organismes (CNCM) at the Institut Pasteur in Paris, France on Dec. 19, 1985 under Accession No. I-502 and has also been deposited at the British ECA CC under No. 87.001.001 on Jan. 9, 1987. A second LAV-II isolate was deposited at CNCM on Feb. 21, 1986 under Accession No. I-532 and has also been deposited at the British ECA CC under No. 87.001.002 on Jan. 9, 1987. This second isolate has been subsequently referred to as LAV-II ROD. Other isolates deposited at the CNCM on Dec. 19, 1986 are HIV-2 IRMO (No. I-642) and HIV-2 EHO (No. I-643). Several additional isolates have been obtained from West African patients, some of whom have AIDS, others with AIDS-related conditions and others with no AIDS symptoms. All of these viruses have been isolated on normal human lymphocyte cultures and some of them were thereafter propagated on lymphoid tumor cell lines such as CEM and MOLT.
Due to the sero-negative or weak sero-positive results obtained when using kits designed to identify HIV-1 infections in the diagnosis of these new patients with HIV-2 disease, it has been necessary to devise a new diagnostic kit capable of detecting HIV-2 infection, either by itself or in combination with an HIV-1 infection. The present inventors have, through the development of cloned DNA sequences analogous to at least a portion of the genomic RNA of LAV-II ROD viruses, created the materials necessary for the development of such kits.
SUMMARY OF THE INVENTION
As noted previously, the present invention relates to the cloned nucleotide sequences homologous or identical to at least a portion of the genomic RNA of HIV-2 viruses and to polypeptides encoded by the same. the present invention also relates to kits capable of diagnosing an HIV-2 infection.
Thus, a main object of the present invention is to provide a kit capable of diagnosing an infection caused by the HIV-2 virus. This kit may operate by detecting at least a portion of the RNA genome of the HIV-2 virus or the provirus present in the infected cells through hybridization with a DNA probe or it may operate through the immunodiagnostic detection of polypeptides unique to the HIV-2 virus.
Additional objects and advantages of the present invention will be set forth in part in the description which follows, or may be learned from practice of the invention. The objects and advantages may be realized and attained by means of the instrumentalities and combinations particularly pointed out in the appended claims.
To achieve these objects and in accordance with the purposes of the present invention, cloned DNA sequences related to the entire genomic RNA of the LAV-II virus are set forth. These sequences are analogous specifically to the entire genome of the LAV-II ROD strain.
To further achieve the objects and in accordance with the purposes of the present invention, a kit capable of diagnosing an HIV-2 infection is described. This kit, in one embodiment, contains the cloned DNA sequences of this invention which are capable of hybridizing to viral RNA or analogous DNA sequences to dicate the presence of an HIV-2 infection. Different diagnostic techniques can be used which include, but are not limited to: (1) Southern blot procedures to identify viral DNA which may or may not be digested with restriction enzymes; (2) Northern blot techniques to identify viral RNA extracted from cells; and (3) dot blot techniques, i.e., direct filtration of the sample through an ad hoc membrane such as nitrocellulose or nylon without previous separation on agarose gel. Suitable material for dot blot technique could be obtained from body fluids including but not limited to, serum and plasma, supernatants from culture cells, or cytoplasmic extracts obtained after cell lysis and removal of membranes and nuclei of the cells by ultra-centrifugation as accomplished in the "CYTODOT" procedure as described in a booklet published by Schleicher and Schull.
In an alternate embodiment, the kit contains the polypeptides created using these cloned DNA sequences. These polypeptides are capable of reacting with antibodies to the HIV-2 virus present in sera of infected individuals, thus yielding an immunodiagnostic complex.
In accordance with a further object of the present invention, a peptide is provided as described above, either alone or conjugated to a carrier molecule, the peptide being capable of eliciting the production of an antibody to the peptide, and said antibody is capable of forming an effective immunocomplex with the entire HIV-2 retrovirus or with its corresponding proteins.
To further achieve the objects of the invention, a vaccinating agent is provided which comprises at least one peptide selected from the polypeptide expression products of the viral DNA in admixture with suitable carriers, adjuvents stabilizers.
It is understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention as claimed. The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate one embodiment of the invention and, together with the description, serve to explain the principles of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 generally depicts the nucleotide sequence of a cloned complementary DNA (cDNA) to the genomic RNA of HIV-2. FIG. 1A depicts the genetic organization of HIV-1, position of the HIV-1 HindIII fragment used as a probe to screen the cDNA library, and restriction map of the HIV-2 cDNA clone, E2. FIG. 1B depicts the nucleotide sequence of the 3' end of HIV-2. The corresponding region of the HIV-1 LTR was aligned using the Wilbur and Lipman algorithm (window: 10; K-tuple: 7; gap penalty: 3) as described by Wilbur and Lipman in Proc. Natl. Acad. Sci. USA 80: 726-730 (1983), specifically incorporated herein by reference. The U3-R junction in HIV-1 is indicated and the poly A addition signal and potential TATA promoter regions are boxed. In FIG. 1A, the symbols B, H, Ps and Pv refer to the restriction sites BamHI, HindIII, PstI and PvuII, respectively.
FIG. 2 generally depicts the HIV-2 specificity of the E2 clone. FIG. 2A and B are line drawings representing Southern Blots of DNA extracted from CEM cells infected with the following isolates: HIV-2 ROD (a,c), HIV-2 DUL (b,d), and HIV-1 BRU (e,f). DNA in lanes a,b,f was Pst I digested; in c,d,e DNA was undigested. FIG. 2C and D are line drawings representing blot hybridization of pelleted virions from CEM cells infected by the HIV-1 BRU (1), Simian Immunodeficiency Virus (SIV) isolate Mm 142-83 (3), HIV-2 DUL (4), HIV-2 ROD (5), and HIV-1 ELI (6). Dot 2 is a pellet from an equivalent volume of supernatant from uninfected CEM. Thus, FIG. 2A and C depict hybridization with the HIV-2 cDNA (E2) and FIG. 2B and D depict hybridization to an HIV-1 probe consisting of a 9 Kb SacI insert from HIV-1 BRU(clone lambda J 19).
FIG. 3 generally depicts a restriction map of the HIV-2 ROD genome and its homology to HIV-1. FIG. 3A specifically depicts the organization of three recombinant phage lambda clones, ROD 4, ROD 27, and ROD 35. In FIG. 3A, the open boxes represent viral sequences, the LTR are filled, and the dotted boxes represent cellular flanking sequences (not mapped). Only some characteristic restriction enzyme sites are indicated. λROD 27 and λROD 35 are derived from integrated proviruses while λROD 4 is derived from a circular viral DNA. The portion of the lambda clones that hybridzes to the cDNA E2 is indicated below the maps. A restriction map of the λROD isolate was reconstructed from these three lambda clones. In this map, the restriction sites are identified as follows: B: BamHI; E: EcoRI; H: HindIII; K: KpnI; PS: PstI; Pv: PvuII; S: SacI; X: XbaI. R and L are the right and left BamHI arms of the lambda L47.1 vector.
FIG. 3B specifically depicts dots 1-11 which correspond to the single-stranded DNA form of M13 subclones from the HIV-1 BRU cloned genome (λJ19). Their size and position on the HIV-1 genome, determined by sequencing is shown below the figure. Dot 12 is a control containing lambda phage DNA. The dot-blot was hybridized in low stringency conditions as described in Example 1 with the complete lambda λROD 4 clone as a probe, and successively washed in 2×SSC, 0.1% SDS at 25° C. (Tm -42° C.), 1×SSC, 0.1% SDS at 60°C. (Tm -20° C.), and 0.1×SSC, 0.1% SDS at 60° C. (Tm -3° C.) and exposed overnight. A duplicate dot blot was hybridized and washed in stringent conditions (as described in Example 2) with the labelled lambda J19 clone carrying the complete HIV-1 BRU genome. HIV-1 and HIV-2 probes were labelled the same specific activity (10 8 cpm/g.).
FIG. 4 generally depicts the restriction map polymorphism in different HIV-2 isolates and shows comparison of HIV-2 to SIV. FIG. 4A is a line drawing depicting DNA (20 ug per lane) from CEM cells infected by the isolate HIV-2 DUL (panel 1) or peripheral blood lymphocytes (PBL) infected by the isolates HIV-2 GOM (panel 2) and HIV-2 MIR (panel 3) digested with: EcoRI (a), PstI (b), and HindIII (c). Much less viral DNA was obtained with HIV-2 isolates propagated on PBL. Hybridization and washing were in stringent conditions, as described in Example 2, with 10 6 cpm/ml. of each of the E2 insert (cDNA) and the 5 kb. HindIII fragment of λROD 4, labelled to 10 9 cpm/g.
FIG. 4B is a line drawing depicting DNA from HUT 78 (a human T lymphoid cell line) cells infected with STLV3 MAC isolate Mm 142-83. The same amounts of DNA and enzymes were used as indicated in panel A. Hybridization was performed with the same probe as in A, but in non-stringent conditions. As described in Example 1 washing was for one hour in 2×SSC, 0.1% SDS at 40° C. (panel 1) and after exposure, the same filter was re-washed in 0.1×SSC, 0.1% SDS at 60° C. (panel 2). The autoradiographs were obtained after overnight exposition with intensifying screens.
FIG. 5 depicts the position of derived plasmids from λROD 27, λROD 35 and λROD 4.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Reference will now be made in detail to the presently preferred embodiments of the invention, which, together with the following examples, serve to explain the principles of the invention.
The genetic structure of the HIV-2 virus has been analyzed by molecular cloning according to the method set forth herein and in the Examples. A restriction map of the genome of this virus is included in FIG. 5. In addition, the partial sequence of a cDNA complementary to the genomic RNA of the virus has been determined. This cDNA sequence information is included in FIG. 1.
Also contained herein is data describing the molecular cloning of the complete 9.5 kb genome of HIV-2, data describing the observation of restriction map polymorphism between different isolates, and an analysis of the relationship between HIV-2 and other human and simian retroviruses. From the totality of these data, diagnostic probes can be discerned and prepared.
Generally, to practice one embodiment of the present invention, a series of filter hybridizations of the HIV-2 RNA genome with probes derived from the complete cloned HIV-1 genome and from the qaq and pol genes were conducted. These hybridizations yielded only extremely weak signals even in conditions of very low stringency of hybridization and washing. Thus, it was found to be difficult to assess the amount of HIV-2 viral and proviral DNA in infected cells by Southern blot techniques.
Therefore, a complementary DNA (cDNA) to the HIV-2 genomic RNA initially was cloned in order to provide a specific hybridization probe. To construct this cDNA, an oligo (dT) primed cDNA first-strand was made in a detergent-activated endogenous reaction using HIV-2 reverse transcriptase with virions purified from supernatants of infected CEM cells. The CEM cell line is a lymphoblastoid CD4+ cell line described by G. E. Foley et al. in Cancer 18: 522-529 (1965), specifically incorporated herein by reference. The CEM cells used were infected with the isolate ROD and were continuously producing high amounts of HIV-2.
After second-strand synthesis, the cDNAs were inserted into the M 13 tg 130 bacteriophage vector. A collection of 10 4 M13 recombinant phages was obtained and screened in situ with an HIV-1 probe spanning 1.5 kb. of the 3' end of the LAV BRU isolate (depicted in FIG. 1A). Some 50 positive plaques were detected, purified, and characterized by end sequencing and cross-hybridizing the inserts. This procedure is described in more detail in Example 1 and in FIG. 1.
The different clones were found to be complementary to the 3' end of a polyadenylated RNA having the AATAAA signal about 20 nucleotides upstream of the poly A tail, as found in the long terminal repeat (LTR) of HIV-1. The LTR region of HIV-1 has been described by S. Wain Hobson et al. in Cell 40: 9-17 (1985), specifically incorporated herein by reference. The portion of the HIV-2 LTR that was sequenced was related only distantly to the homologous domain in HIV-1 as demonstrated in FIG. 1B. Indeed, only about 50% of the nucleotides could be aligned and about a hundred insertions/deletions need to be introduced. In comparison, the homology of the corresponding domains in HIV-1 isolates from USA and Africa is greater than 95% and no insertions or deletions are seen.
The largest insert of this group of M13 clones was a 2 kb. clone designated E2. Clone E2 was used as a probe to demonstrate its HIV-2 specificity in a series of filter hybridization experiments. Firstly, this probe could detect the genomic RNA of HIV-2 but not HIV-1 in stringent conditions as shown in FIG. 2, C and D. Secondly, positive signals were detected in Southern blots of DNA from cells infected with the ROD isolate as well as other isolates of HIV-2 as shown in FIG. 2, A and FIG. 4, A. No signal was detected with DNA from uninfected cells or HIV-1 infected cells, confirming the exogenous nature of HIV-2. In undigested DNA from HIV-2 infected cells, an approximately 10 kb. species, probably corresponding to linear unintegrated viral DNA, was principally detected along with a species with an apparent size of 6 kb., likely to be the circular form of the viral DNA. Conversely, rehybridization of the same filter with an HIV-1 probe under stringent conditions showed hybridization to HIV-1 infected cells only as depicted in FIG. 2, B.
To isolate the remainder of the genome of HIV-2, a genomic library in lambda phage L47.1 was constructed. Lambda phage L47.1 has been described by W. A. M. Loenen et al. in Gene 10: 249-259 (1980), specifically incorporated herein by reference. The genomic library was constructed with a partial Sau3AI restriction digest of the DNA from the CEM cell line infected with HIV-2 ROD .
About 2×10 6 recombinant plaques were screened in situ with labelled insert from the E2 cDNA clone. Ten recombinant phages were detected and plaque purified. Of these phages, three were characterized by restriction mapping and Southern blot hybridization with the E2 insert and probes from its 3' end (LTR) or 5' end (envelope), as well as with HIV-1 subgenomic probes. In this instance, HIV-1 probes were used under non-stringent conditions.
A clone carrying a 9.5 kb. insert and derived from a circular viral DNA was identified as containing the complete genome and designated λROD 4. Two other clones, λROD 27 and λROD 35 were derived from integrated proviruses and found to carry an LTR and cellular flanking sequences and a portion of the viral coding sequences as shown in FIG. 3, A.
Fragments of the lambda clones were subcloned into a plasmid vector p UC 18.
Plasmid pROD 27-5' is derived from λROD 27 and contains the 5' 2 Kb of the HIV-2 genome and cellular flanking sequences (5' LTR and 5' viral coding sequences to the EcoRI site)
Plasmid p ROD 4-8 is dervied from λROD 4 and contains the about 5Kb HindIII fragment that is the central part of the HIV-2 genome.
Plasmid pROD 27-5' and p ROD 4.8 inserts overlap.
Plasmid pROD 4.7 contains a HindIII 1.8 Kb fragment from λROD 4. This fragment is located 3' to the fragment subcloned into pROD 4.8 and contains about 0.8 Kb of viral coding sequences and the part of the lambda phage (λL47.1) left arm located between the BamHI and HindIII cloning sites.
Plasmid pROD 35 contains all the HIV-2 coding sequences 3' to the EcoRI site, the 3' LTR and about 4 Kb of cellular flanking sequences.
Plasmid pROD 27-5' and pROD 35 in E. coli strain HB 101 are deposited respectively under No. I-626 and I-633 at the CNCM, and have also been deposited at the NCIB (British Collection). These plasmids are depicted in FIG. 5. Plasmids pROD 4-7 and pROD 4-8 in E. coli strain TGl are deposited respectively under No. I-627 and I-628 at the CNCM.
To reconstitute the complete HIV-2 ROD genome, pROD 35 is linearized with EcoRI and the EcoRI insert of pROD 27-5' is ligated in the correct orientation into this site.
The relationship of HIV-2 to other human and simian retroviruses was surmised from hybridization experiments. The relative homology of the different regions of the HIV-1 and 2 genomes was determined by hybridization of fragments of the cloned HIV-1 genome with the labelled λROD 4 expected to contain the complete HIV-2 genome (FIG. 3, B). Even in very low stringency conditions (Tm -42° C.), the hybridization of HIV-1 and 2 was restricted to a fraction of their genomes, principally the qaq gene (dots 1 and 2), the reverse transcriptase domain in pol (dot 3), the end of pol and the Q (or sor) genes (dot 5) and the F gene (or 3' orf) and 3' LTR (dot 11). The HIV-1 fragment used to detect the HIV-2 cDNA clones contained the dot 11 subclone, which hybridized well to HIV-2 under non-stringent conditions. Only the signal from dot 5 persisted after stringent washing. The envelope gene, the region of the tat gene and a part of pol thus seemed very divergent. These data, along with the LTR sequence obtained (FIG. 1, B), indicated that HIV-2 is not an envelope variant of HIV-1, as are African isolates from Zaire described by Alizon et al., Cell 40:63-74 (1986).
It was observed that HIV-2 is related more closely to the Simian Immunodeficiency Virus (SIV) than it is to HIV-1. This correlation has been described by F. Clavel et al. in C.R. Acad. Sci. (Paris) 302: 485-488 (1986) and F. Clavel et al. in Science 233: 343-346 (1986), both of which are specifically incorporated herein by reference. Simian Immunodeficiency Virus (also designated Simian T-cell Lymphotropic Virus Type 3, STLV-3) is a retrovirus first isolated from captive macaques with an AIDS-like disease in the USA. This simian virus has been described by M. D. Daniel et al. in Science 228: 1201-1204 (1985), specifically incorporated herein by reference.
All the SIV proteins, including the envelope, are immune precipitated by sera from HIV-2 infected patients, whereas the serological cross-reactivity of HIV-1 to 2 is restricted to the core proteins. However SIV and HIV-2 can be distinguished by slight differences in the apparent molecular weight of their proteins.
In terms of nucleotide sequence, it also appears that HIV-2 is closely related to SIV. The genomic RNA of SIV can be detected in stringent conditions as shown in FIG. 2, C by HIV-2 probes corresponding to the LTR and 3' end of the genome (E2) or to the qaq or pol genes. Under the same conditions, HIV-1derived probes do not detect the SIV genome as shown in FIG. 2, D.
In Southern blots of DNA from SIV-infected cells, a restriction pattern clearly different from HIV-2 ROD and other isolates is seen. All the bands persist after a stringent washing, even though the signal is considerably weakened, indicating a sequence homology throughout the genomes of HIV-2 and SIV. It has recently been shown that baboons and macaques could be infected experimentally by HIV-2, thereby providing an interesting animal model for the study of the HIV infection and its preventive therapy. Indeed, attempts to infect non-human primates with HIV-1 have been successful only in chimpanzees, which are not a convenient model.
From an initial survey of the restriction maps for certain of the HIV-2 isolates obtained according to the methods described herein, it is already apparent that HIV-2, like HIV-1, undergoes restriction site polymorphism. FIG. 4 A depicts examples of such differences for three isolates, all different one from another and from the cloned HIV-2 ROD . It is very likely that these differences at the nucleotide level are accompanied by variations in the amino-acid sequence of the viral proteins, as evidenced in the case of HIV-1 and described by M. Alizon et al. in Cell 46: 63-74 (1986), specifically incorporated herein by reference. It is also to be expected that the various isolates of HIV-2 will exhibit amino acid heterogeneities. See, for example, Clavel et al., Nature 324 (18):691-695 (1986), specifically incorporated herein by reference.
Further, the chacterization of HIV-2 will also delineate the domain of the envelope glycoprotein that is responsible for the binding of the surface of the target cells and the subsequent internalization of the virus. This interaction was shown to be mediated by the CD4 molecule itself in the case of HIV-1 and similar studies tend to indicate that HIV-2 uses the same receptor. Thus, although there is wide divergence between the env genes of HIV-1 and 2, small homologous domains of the envelopes of the two HIV could represent a candidate receptor binding site. This site could be used to raise a protective immune response against this group of retroviruses.
From the data discussed herein, certain nucleotide sequences have been identified which are capable of being used as probes in diagnostic methods to obtain the immunological reagents necessary to diagnose an HIV-2 infection. In particular, these sequences may be used as probes in hybridization reactions with the genetic material of infected patients to indicate whether the RNA of the HIV-2 virus is present in these patient's lymphocytes or whether an analogous DNA is present. In this embodiment, the test methods which may be utilized include Northern blots, Southern blots and dot blots. One particular nucleotide sequence which may be useful as a probe is the combination of the 5 kb. HindIII fragment of ROD 4 and the E2 cDNA used in FIG. 4.
In addition, the genetic sequences of the HIV-2 virus may be used to create the polypeptides encoded by these sequences. Specifically, these polypeptides may be created by expression of the cDNA obtained according to the teachings herein in hosts such as bacteria, yeast or animal cells. These polypeptides may be used in diagnostic tests such as immunofluorescence assays (IFA), radioimmunoassays (RIA) and Western Blot tests.
Moreover, it is also contemplated that additional diagnostic tests, including additional immunodiagnostic tests, may be developed in which the DNA probes or the polypeptides of this invention may serve as one of the diagnostic reagents. The invention described herein includes these additional test methods.
In addition, monoclonal antibodies to these polypeptides or fragments thereof may be created. The monoclonal antibodies may be used in immunodiagnostic tests in an analogous manner as the polypeptides described above.
The polypeptides of the present invention may also be used as immunogenic reagents to induce protection against infection by HIV-2 viruses. In this embodiment, the polypeptides produced recombinant-DNA techniques would function as vaccine agents. Also, the polypeptides of this invention may be used in competitive assays to test the ability of various antiviral agents to determine their ability to prevent the virus from fixing on its target.
Thus, it is to be understood that application of the teachings of the present invention to a specific problem or environment will be within the capabilities of one having ordinary skill in the art in light of the teachings contained herein. Examples of the products of the present invention and representative processes for their isolation and manufacture appear above and in the following examples.
EXAMPLES
Example 1
Cloning of a cDNA Complementary to Genomic RNA From HIV-2 Virions
HIV-2 virions were purified from 5 liters of supernatant from a culture of the CEM cell line infected with the ROD isolate and a cDNA first strand using oligo (dT) primer was synthesized in detergent activated endogenous reaction on pelleted virus, as described by M. Alizon et al. in Nature, 312: 757-760 (1984), specifically incorporated herein by reference. RNA-cDNA hybrids were purified by phenol-chloroform extraction and ethanol precipitation. The second-strand cDNA was created by the DNA polymerase I/RNAase H method of Gubler and Hoffman in Gene, 25: 263-269 (1983), specifically incorporated herein by reference, using a commercial cDNA synthesis kit obtained from Amersham. After attachment of EcoRI linkers (obtained from Pharmacia), EcoRI digestion, and ligation into EcoRI-digested dephosphorylated M13 tg 130 vector (obtained from Amersham), a cDNA library was obtained by transformation of the E. coli TGl strain. Recombinant plaques (10 4 ) were screened in situ on replica filters with the 1.5 kb. HindIII fragment from clone J19, corresponding to the 3' part of the genome of the LAV BRU isolate of HIV-1, 32 p labelled to a specific activity of 10 9 cpm/ug. The filters were prehybridized in 5×SSC, 5× Denhardt solution, 25% formamide, and denatured salmon sperm DNA (100 mg/ml) at 37° C. for 4 hours and hybridized for 16 hours in the same buffer (Tm -42° C.) plus 4×10 7 cpm of the labelled probe (10 6 cpm/ml. of hybridization buffer). The washing was done in 5×SSC, 0.1% SDS at 25° C. for 2 hours. 20×SSC is 3M NaCl, 0.3M Na citrate. Positive plaques were purified and single-stranded M13 DNA prepared and end-sequenced according to the method described in Proc. Nat'l. Acad. Sci. USA, 74: 5463-5467 (1977) of Sanger et al.
Example 2
Hybridization of DNA from HIV-1 and HIV-2 Infected Cells and RNA from HIV-1and 2 and SIV Virons With a Probe Derived From an HIV-2 Cloned cDNA
DNA was extracted from infected CEM cells continuously producing HIV-1 or 2. The DNA digested with 20 g of PstI or undigested, was electrophoresed on a 0.8% agarose gel, and Southern-transferred to nylon membrane. Virion dot-blots were prepared in duplicate, as described by F. Clavel et al. in Science 233: 343-346 (1986), specifically incorporated herein by reference, by pelleting volumes of supernatant corresponding to the same amount of reverse transcriptase activity. Prehybridization was done in 50% formamide, 5×SSC, 5× Denhardt solution, and 100 mg./ml. denatured salmon sperm DNA for 4 hours at 42° C. Hybridization was performed in the same buffer plus 10% Dextran sulphate, and 10 6 cpm/ml. of the labelled E2 insert (specific activity 10 9 cpmg) for 16 hours at 42° C. Washing was in 0.1×SSC, 0.1% SDS for 2×30 mn. After exposition for 16 hours with intensifying screens, the Southern blot was dehybridized in 0.4 N NaOH, neutralized, and rehybridized in the same conditions to the HIV-1 probe labelled to 10 9 cpmg.
Example 3
Cloning in Lambda Phage of the Complete Provirus DNA of HIV-2
DNA from the HIV-2 ROD infected CEM (FIG. 2, lanes a and c) was partially digested with Sau3AI. The 9-15 kb. fraction was selected on a 5-40% sucrose gradient and ligated to BamHI arms of the lambda L47.1 vector. Plaques (2×10 6 ) obtained after in vitro packaging and plating on E. coli LA 101 strain were screened in situ with the insert from the E2 cDNA clone. Approximately 10 positive clones were plaque purified and propagated on E. coli C600 recBC. The ROD 4, 27, and 35 clones were amplified and their DNA characterized by restriction mapping and Southern blotting with the HIV-2 cDNA clone under stringent conditions, and gag-pol probes from HIV-1 used under non stringent conditions.
Example 4
Complete Genomic Sequence of the ROD HIV-2 Isolate
Experimental analysis of the HIV-2 ROD isolate yielded the following sequence which represents the complete genome of this HIV-2 isolate. Genes and major expression products identified within the following sequence are indicated by nucleotides numbered below:
1) GAG gene (546-2111) expresses a protein product having a molecular weight of around 55 KD and is cleaved into the following proteins:
a) p 16 (546-950)
b) p 26 (951-1640)
c) p 12 (1701-2111)
2) polymerase (1829-4936)
3) Q protein (4869-5513)
4) R protein (5682-5996)
5) X protein (5344-5679)
6) Y protein (5682-5996)
7) Env protein (6147-8720)
8) F protein (8557-9324)
9) TAT gene (5845-6140 and 8307-8400) is expressed by two exons separated by introns.
10) ART protein (6071-6140 and 8307-8536) is similarly the expression product of two exons.
11) LTR:R (1-173 and 9498-9671)
12) U5 (174-299)
13) U3 (8942-9497)
It will be known to one of skill in the art that the absolute numbering which has been adopted is not essential. For example, the nucleotide within the LTR which is designated as "1" is a somewhat arbitrary choice. What is important is the sequence information provided. GGTCGCTCTGCGGAGAGGCTGGCAGATTGAGCCCTGGGAGGTTCTCTCCAGCACTAGCAG . . . . . . - GTAGAGCCTGGGTGTTCCCTGCTAGACTCTCACCAGCACTTGGCCGGTGCTGGGCAGACG . . . 100 . . - GCCCCACGCTTGCTTGCTTAAAAACCTC TTAATAAAGCTGCCAGTTAGAAGCAAGTTAAG . . . . . . - TGTGTGCTCCCATCTCTCCTAGTCGCCG CCTGGTCATTCGGTGTTCACCTGAGTAACAAG . 200 . . . . - ACCCTGGTCTGTTAGGACCCTTCTTGCT TTGGGAAACCGAGGCAGGAAAATCCCTAGCAG . . . . . 300 - GTTGGCGCCTGAACAGGGACTTGAAGAA GACTGAGAAGTCTTGGAACACGGCTGAGTGAA . . . . . . - GGCAGTAAGGGCGGCAGGAACAAACCAC GACGGAGTGCTCCTAGAAAGGCGCGGGCCGAG . . . 400 . . - GTACCAAAGGCAGCGTGTGGAGCGGGAG GAGAAGAGGCCTCCGGGTGAAGGTAAGTACCT . . . . . . - ACACCAAAAACTGTAGCCGAAAGGGCTT GCTATCCTACCTTTAGACAGGTAGAAGATTGT . 500 . . . . - MetGlyAlaArgAsnSerValLe uArgGlyLysLysAlaAspGluLeuGluArgIle GGGAGATGGGCGCGAGAAACTCCGTCTTGAGAGGGAAAAAAGCAGATGAATTAGAAAGAA . . . . . 600 - ArgLeuArgProGlyGlyLysLysLysTyrArgLeuLysHisIleValTrpAlaAlaAsn TCAGGTTACGGCCCGGCGGAAAGAAAAAGTA CAGGCTAAAACATATTGTGTGGGCAGCGA . . . . . . - LysLeuAspArgPheGlyLeuAlaGl uSerLeuLeuGluSerLysGluGlyCysGlnLys ATAAATTGGACAGATTCGGATTAGCAGAGAGCCTGTTGGAGTCAAAAGAGGGTTGTCAAA . . . 700 . . - IleLeuThrValLeuAspProMetValProThrGlySerGluAsnLeuLysSerLeuPhe AAATTCTTACAGTTTTAGATCCAATGGTACC GACAGGTTCAGAAAATTTAAAAAGTCTTT . . . . . . - AsnThrValCysValIleTrpCysIl eHisAlaGluGluLysValLysAspThrGluGly TTAATACTGTCTGCGTCATTTGGTGCATACACGCAGAAGAGAAAGTGAAAGATACTGAAG . 800 . . . . - AlaLysGlnIleValArgArgHisLeuValAlaGluThrGlyThrAlaGluLysMetPro GAGCAAAACAAATAGTGCGGAGACATCTAGT GGCAGAAACAGGAACTGCAGAGAAAATGC . . . . . 900 - SerThrSerArgProThrAlaProSe rSerGluLysGlyGlyAsnTyrProValGlnHis CAAGCACAAGTAGACCAACAGCACCATCTAGCGAGAAGGGAGGAAATTACCCAGTGCAAC . . . . . . - ValGlyGlyAsnTyrThrHisIleProLeuSerProArgThrLeuAsnAlaTrpValLys ATGTAGGCGGCAACTACACCCATATACCGCT GAGTCCCCGAACCCTAAATGCCTGGGTAA . . . 1000 . . - LeuValGluGluLysLysPheGlyAl aGluValValProGlyPheGlnAlaLeuSerGlu AATTAGTAGAGGAAAAAAAGTTCGGGGCAGAAGTAGTGCCAGGATTTCAGGCACTCTCAG . . . . . . - GlyCysThrProTyrAspIleAsnGlnMetLeuAsnCysValGlyAspHisGlnAlaAla AAGGCTGCACGCCCTATGATATCAACCAAAT GCTTAATTGTGTGGGCGACCATCAAGCAG . 1100 . . . . - MetGlnIleIleArgGluIleIleAs nGluGluAlaAlaGluTrpAspValGlnLisPro CCATGCAGATAATCAGGGAGATTATCAATGAGGAAGCAGCAGAATGGGATGTGCAACATC . . . . . 1200 - IleProGlyProLeuProAlaGlyGlnLeuArgGluProArgGlySerAspIleAlaGly CAATACCAGGCCCCTTACCAGCGGGGCAGCT TAGAGAGCCAAGGGGATCTGACATAGCAG . . . . . . - ThrThrSerThrValGluGluGlnIl eGlnTrpMetPheArgProGlnAsnProValPro GGACAACAAGCACAGTAGAAGAACAGATCCAGTGGATGTTTAGGCCACAAAATCCTGTAC . . . . 1300 . - ValGlyAsnIleTyrArgArgTrpIleGlnIleGlyLeuGlnLysCysValArgMetTyr CAGTAGGAAACATCTATAGAAGATGGATCCA GATAGGATTGCAGAAGTGTGTCAGGATGT . . . . . . - AsnProThrAsnIleLeuAspIleLy sGlnGlyProLysGluProPheGlnSerTyrVal ACAACCCGACCAACATCCTAGACATAAAACAGGGACCAAAGGAGCCGTTCCAAAGCTATG . 1400 . . . . - AspArgPheTyrLysSerLeuArgAlaGluGlnThrAspProAlaValLysAsnTrpMet TAGATAGATTCTACAAAAGCTTGAGGGCAGA ACAAACAGATCCAGCAGTGAAGAATTGGA . . . . . 1500 - ThrGlnThrLeuLeuValGlnAsnAl aAsnProAspCysLysLeuValLeuLysGlyLeu TGACCCAAACACTGCTAGTACAAAATGCCAACCCAGACTGTAAATTAGTGCTAAAAGGAC . . . . . . - GlyMetAsnProThrLeuGluGluMetLeuThrAlaCysGlnGlyValGlyGlyProGly TAGGGATGAACCCTACCTTAGAAGAGATGCT GACCGCCTGTCAGGGGGTAGGTGGGCCAG . . . 1600 . . - GlnLysAlaArgLeuMetAlaGluAl aLeuLysGluValIleGlyProAlaProIlePro GCCAGAAAGCTAGATTAATGGCAGAGGCCCTGAAAGAGGTCATAGGACCTGCCCCTATCC . . . . . . - PheAlaAlaAlaGlnGlnArgLysAlaPheLysCysTrpAsnCysGlyLysGluGlyHis CATTCGCAGCAGCCCAGCAGAGAAAGGCATT TAAATGCTGGAACTGTGGAAAGGAAGGGC . 1700 . . . . - SerAlaArgGlnCysArgAlaProAr gArgGlnGlyCysTrpLysCysGlyLysProGly ACTCGGCAAGACAATGCCGAGCACCTAGAAGGCAGGGCTGCTGGAAGTGTGGTAAGCCAG . . . . . 1800 - ThrGlyArgPhePheArgThrGlyProLeuGly HisIleMetThrAsnCysProAspArgG lnAlaGlyPheLeuGlyLeuGlyProTrpGly GACACATCATGACAAACTGCCCAGATAGACA GGCAGGTTTTTTAGGACTGGGCCCTTGGG . . . . . . - LysGluAlaProGlnLeuProArgGly ProSerSerAlaGlyAlaAspThrAsnSerThr LysLysProArgAsnPheProValAlaGlnValProGlnGlyLeuThrProThrAlaPro GAAAGAAGCCCCGCAACTTCCCCGTGGCCCA AGTTCCGCAGGGGCTGACACCAACAGCAC . . . 1900 . . - ProSerGlySerSerSerGlySerThr GlyGluIleTyrAlaAlaArgGluLysThrGlu ProValAspProAlaValAspLeuLeuGluLysTyrMetGlnGlnGlyLysArgGlnArg CCCCAGTGGATCCAGCAGTGGATCTACTGGA GAAATATATGCAGCAAGGGAAAAGACAGA . . . . . . - ArgAlaGluArgGluThrIleGlnGly SerAspArgGlyLeuThrAlaProArgAlaGly GluGlnArgGluArgProTyrLysGluValThrGluAspLeuLeuHisLeuGluGlnGly GAGAGCAGAGAGAGAGACCATACAAGGAAGT GACAGAGGACTTACTGCACCTCGAGCAGG . 2000 . . . . - GlyAspThrIleGlnGlyAlaThrAsn ArgGlyLeuAlaAlaProGlnPheSerLeuTrp GluThrProTyrArgGluProProThrGluAspLeuLeuHisLeuAsnSerLeuPheGly GGGAGACACCATACAGGGAGCCACCAACAGA GGACTTGCTGCACCTCAATTCTCTCTTTG . . . . . 2100 - LysArgProValValThrAlaTyrIle GluGlyGlnProValGluValLeuLeuAspThr LysAspGln GAAAAGACCAGTAGTCACAGCATACATTGAGGGTCAGCCAGTAGAAGTCTTGTTAGACAC . . . . . . - GlyAlaAspAspSerIleValAlaGlyIleGluLeuGlyAsnAsnTyrSerProLysIle AGGGGCTGACGACTCAATAGTAGCAGGAATA GAGTTAGGGAACAATTATAGCCCAAAAAT . . . 2200 . . - ValGlyGlyIleGlyGlyPheIleAsn ThrLysGluTyrLysAsnValGluIleGluVal AGTAGGGGGAATAGGGGGATTCATAAATACCAAGGAATATAAAAATGTAGAAATAGAAGT . . . . . . - LeuAsnLysLysValArgAlaThrIleMetThrGlyAspThrProIleAsnIlePheGly TCTAAATAAAAAGGTACGGGCCACCATAATG ACAGGCGACACCCCAATCAACATTTTTGG . 2300 . . . . - ArgAsnIleLeuThrAlaLeuGlyMet SerLeuAsnLeuProValAlaLysValGluPro CAGAAATATTCTGACAGCCTTAGGCATGTCATTAAATCTACCAGTCGCCAAAGTAGAGCC . . . . . 2400 - IleLysIleMetLeuLysProGlyLysAspGlyProLysLeuArgGlnTrpProLeuThr AATAAAAATAATGCTAAAGCCAGGGAAAGAT GGACCAAAACTGAGACAATGGCCCTTAAC . . . . . . - LysGluLysIleGluAlaLeuLysGlu IleCysGluLysMetGluLysGluGlyGlnLeu AAAAGAAAAAATAGAAGCACTAAAAGAAATCTGTGAAAAAATGGAAAAAGAAGGCCAGCT . . . 2500 . . - GluGluAlaProProThrAsnProTyrAsnThrProThrPheAlaIleLysLysLysAsp AGAGGAAGCACCTCCAACTAATCCTTATAAT ACCCCCACATTTGCAATCAAGAAAAAGGA . . . . . . - LysAsnLysTrpArgMetLeuIleAsp PheArgGluLeuAsnLysValThrGlnAspPhe CAAAAACAAATGGAGGATGCTAATAGATTTCAGAGAACTAAACAAGGTAACTCAAGATTT . 2600 . . . . - ThrGluIleGlnLeuGlyIleProHisProAlaGlyLeuAlaLysLysArgArgIleThr CACAGAAATTCAGTTAGGAATTCCACACCCA GCAGGGTTGGCCAAGAAGAGAAGAATTAC . . . . . 2700 - ValLeuAspValGlyAspAlaTyrPhe SerIleProLeuHisGluAspPheArgProTyr TGTACTAGATGTAGGGGATGCTTACTTTTCCATACCACTACATGAGGACTTTAGACCATA . . . . . . - ThrAlaPheThrLeuProSerValAsnAsnAlaGluProGlyLysArgTyrIleTyrLys TACTGCATTTACTCTACCATCAGTGAACAAT GCAGAACCAGGAAAAAGATACATATATAA . . . 2800 . . - ValLeuProGlnGlyTrpLysGlySer ProAlaIlePheGlnHisThrMetArgGlnVal AGTCTTGCCACAGGGATGGAAGGGATCACCAGCAATTTTTCAACACACAATGAGACAGGT . . . . . . - LeuGluProPheArgLysAlaAsnLysAspValIleIleIleGlnTyrMetAspAspIle ATTAGAACCATTCAGAAAAGCAAACAAGGAT GTCATTATCATTCAGTACATGGATGATAT . 2900 . . . . - LeuIleAlaSerAspArgThrAspLeu GluHisAspArgValValLeuGlnLeuLysGlu CTTAATAGCTAGTGACAGGACAGATTTAGAACATGATAGGGTAGTCCTGCAGCTCAAGGA . . . . . 3000 - LeuLeuAsnGlyLeuGlyPheSerThrProAspGluLysPheGlnLysAspProProTyr ACTTCTAAATGGCCTAGGATTTTCTACCCCA GATGAGAAGTTCCAAAAAGACCCTCCATA . . . . . . - HisTrpMetGlyTyrGluLeuTrpPro ThrLysTrpLysLeuGlnLysIleGlnLeuPro CCACTGGATGGGCTATGAACTATGGCCAACTAAATGGAAGTTGCAGAAAATACAGTTGCC . . . 3100 . . - GlnLysGluIleTrpThrValAsnAspIleGlnLysLeuValGlyValLeuAsnTrpAla CCAAAAAGAAATATGGACAGTCAATGACATC CAGAAGCTAGTGGGTGTCCTAAATTGGGC . . . . . . - AlaGlnLeuTyrProGlyIleLysThr LysHisLeuLysArgLeuIleArgGlyLysMet AGCACAACTCTACCCAGGGATAAAGACCAAACACTTATGTAGGTTAATCAGAGGAAAAAT . 3200 . . . . - ThrLeuThrGluGluValGlnTrpThrGluLeuAlaGluAlaGluLeuGluGluAsnArg GACACTCACAGAAGAAGTACAGTGGACAGAA TTACCAGAAGCAGAGCTAGAAGAAAACAG . . . . . 3300 - IleIleLeuSerGlnGluGlnGluGly HisTyrTyrGlnGluGluLysGluLeuGluAla AATTATCCTAAGCCAGGAACAAGAGGGACACTATTACCAAGAAGAAAAAGAGCTAGAAGC . . . . . . - ThrValGlnLysAspGlnGluAsnGlnTrpThrTyrLysIleHisGlnGluGluLysIle AACAGTCCAAAAGGATCAAGAGAATCAGTGG ACATATAAAATACACCAGGAAGAAAAAAT . . . 3400 . . - LeuLysValGlyLysTyrAlaLysVal LysAsnThrHisThrAsnGlyIleArgLeuLeu TCTAAAAGTAGGAAAATATGCAAAGGTGAAAAACACCCATACCAATGGAATCAGATTGTT . . . . . . - AlaGlnValValGlnLysIleGlyLysGluAlaLeuValIleTrpGlyArgIleProLys AGCACAGGTAGTTCAGAAAATAGGAAAAGAA GCACTAGTCATTTGGGGACGAATACCAAA . 3500 . . . . - PheHisLeuProValGluArgGluIle TrpGluGlnTrpTrpAspAsnTyrTrpGlnVal ATTTCACCTACCAGTAGAGAGAGAAATCTGGGAGCAGTGGTGGGATAACTACTGGCAAGT . . . . . 3600 - ThrTrpIleProAspTrpAspPheValSerThrProProLeuValArgLeuAlaPheAsn GACATGGATCCCAGACTGGGACTTCGTGTCT ACCCCACCACTGGTCAGGTTAGCGTTTAA . . . . . . - LeuValGlyAspProIleProGlyAla GluThrPheTyrThrAspGlySerCysAsnArg CCTGGTAGGGGATCCTATACCAGGTGCAGAGACCTTCTACACAGATGGATCCTGCAATAG . . . 3700 . . - GlnSerLysGluGlyLysAlaGlyTyrValThrAspArgGlyLysAspLysValLysLys GCAATCAAAAGAAGGAAAAGCAGGATATGTA ACAGATAGAGGGAAAGACAAGGTAAAGAA . . . . . . - LeuGluGlnThrThrAsnGlnGlnAla GluLeuGluAlaPheAlaMetAlaLeuThrAsp ACTAGAGCAAACTACCAATCAGCAAGCAGAACTAGAAGCCTTTGCGATGGCACTAACAGA . 3800 . . . . - SerGlyProLysValAsnIleIleValAspSerGlnTyrValMetGlyIleSerAlaSer CTCGGGTCCAAAAGTTAATATTATAGTAGAC TCACAGTATGTAATGGGGATCAGTGCAAG . . . . . 3900 - GlnProThrGluSerGluSerLysIle ValAsnGlnIleIleGluGluMetIleLysLys CCAACCAACAGAGTCAGAAAGTAAAATAGTGAACCAGATCATAGAAGAAATGATAAAAAA . . . . . . - GluAlaIleTyrValAlaTrpValProAlaHisLysGlyIleGlyGlyAsnGlnGluVal GGAAGCAATCTATGTTGCATGGGTCCCAGCC CACAAAGGCATAGGGGGAAACCAGGAAGT . . . 4000 . . - AspHisLeuValSerGlnGlyIleArg GlnValLeuPheLeuGluLysIleGluProAla AGATCATTTAGTGAGTCAGGGTATCAGACAAGTGTTGTTCCTGGAAAAAATAGAGCCCGC . . . . . . - GlnGluGluHisGluLysTyrHisSerAsnValLysGluLeuSerHisLysPheGlyIle TCAGGAAGAACATGAAAAATATCATAGCAAT GTAAAAGAACTGTCTCATAAATTTGGAAT . 4100 . . . . - ProAsnLeuValAlaArgGlnIleVal AsnSerCysAlaGlnCysGlnGlnLysGlyGlu ACCCAATTTAGTGGCAAGGCAAATAGTAAACTCATGTGCCCAATGTCAACAGAAAGGGGA . . . . . 4200 - AlaIleHisGlyGlnValAsnAlaGluLeuGlyThrTrpGlnMetAspCysThrHisLeu AGCTATACATGGGCAAGTAAATGCAGAACTA GGCACTTGGCAAATGGACTGCACACATTT . . . . . . - GluGlyLysIleIleIleValAlaVal HisValAlaSerGlyPheIleGluAlaGluVal AGAAGGAAAGATCATTATAGTAGCAGTACATGTTGCAAGTGGATTTATAGAAGCAGAAGT . . . 4300 . . - IleProGlnGluSerGlyArgGlnThrAlaLeuPheLeuLeuLysLeuAlaSerArgTrp CATCGCACAGGAATCAGGAAGACAAACAGCA CTCTTCCTATTGAAACTGGCAAGTAGGTG . . . . . . - ProIleThrHisLeuHisThrAspAsn GlyAlaAsnPheThrSerGlnGluValLysMet GCCAATAACACACTTGCATACAGATAATGGTGCCAACTTCACTTCACAGGAGGTGAAGAT . 4400 . . . . - ValAlaTrpTrpIleGlyIleGluGlnSerPheGlyValProTyrAsnProGlnSerGln GGTAGCATGGTGGATAGGTATAGAACAATCC TTTGGAGTACCTTACAATCCACAGAGCCA . . . . . 4500 - GlyValValGluAlaMetAsnHisHis LeuLysAsnGlnIleSerArgIleArgGluGln AGGAGTAGTAGAAGCAATGAATCACCATCTAAAAAACCAAATAAGTAGAATCAGAGAACA . . . . . . - AlaAsnThrIleGluThrIleValLeuMetAlaIleHisCysMetAsnPheLysArgArg GGCAAATACAATAGAAACAATAGTACTAATG GCAATTCATTGCATGAATTTTAAAAGAAG . . . 4600 . . - GlyGlyIleGlyAspMetThrProSerG luArgLeuIleAsnMetIleThrThrGluGln GGGGGGAATAGGGGATATGACTCCATCAGAA AGATTAATCAATATGATCACCACAGAACA . . . . . . - GluIleGlnPheLeuGlnAlaLysAsn SerLysLeuLysAspPheArgValTyrPheArg AGAGATACAATTCCTCCAAGCCAAAAATTCAAAATTAAAAGATTTTCGGGTCTATTTCAG . 4700 . . . . - GluGlyArgAspGlnLeuTrpLysGlyProGlyGluLeuLeuTrpLysGlyGluGlyAla AGAAGGCAGAGATCAGTTGTGGAAAGGACCT GGGGAACTACTGTGGAAAGGAGAAGGAGC . . . . . 4800 - ValLeuValLysValGlyThrAspIle LysIleIleProArgArgLysAlaLysIleIle AGTCCTAGTCAAGGTAGGAACAGACATAAAAATAATACCAAGAAGGAAAGCCAAGATCAT . . . . . . - ArgAspTyrGlyGlyArgGlnGluMetAspSerGlySerHisLeuGluGlyAlaArgGlu MetGluGluAspLysArgTrpIl eValValProThrTrpArgValProGlyArg CAGAGACTATGGAGGAAGACAAGAGATGGAT AGTGGTTCqCACCTGGAGGGTGCCAGGGA . . . 4900 . . - AspGlyGluMetAla MetGluLysTrpHisSerLeuValLysTyrLeuLysTyrLysThrLysAspLeuGluLys GGATGGAGAAATGGCATAGCCTTGTCAAGTA TCTAAAATACAAAACAAAGGATCTAGAAA . . . . . . - ValCysTyrValProHisHisLysVa lGlyTrpAlaTrpTrpThrCysSerArgValIle AGGTGTGCTATGTTCCCCACCATAAGGTGGGATGGGCATGGTGGACTTGCAGCAGGGTAA . 5000 . . . . - PheProLeuLysGlyAsnSerHisLeuGluIleGlnAlaTyrTrpAsnLeuThrProGlu TATTCCCATTAAAAGGAAACAGTCATCTAGA GATACAGGCATATTGGAACTTAACACCAC . . . . . 5100 - LysGlyTrpLeuSerSerTyrSerVa lArgIleThrTrpTyrThrGluLysPheTrpThr AAAAAGGATGGCTCTCCTCTTATTCAGTAAGAATAACTTGGTACACAGAAAAGTTCTGGA . . . . . . - AspValThrProAspCysAlaAspValLeuIleHisSerThrTyrPheProCysPheThr CAGATGTTACCCCAGACTGTGCAGATGTCCT AATACATAGCACTTATTTCCCTTGCTTTA . . . 5200 . . - AlaGlyGluValArgArgAlaIleAr gGlyGluLysLeuLeuSerCysCysAsnTyrPro CAGCAGGTGAAGTAAGAAGAGCCATCAGAGGGGAAAAGTTATTGTCCTGCTGCAATTATC . . . . . . - ArgAlaHisArgAlaGlnValProSerLeuGlnPheLeuAlaLeuValValValGlnGln CCCGAGCTCATAGAGCCCAGGTACCGTCACT TCAATTTCTGGCCTTAGTGGTAGTGCAAC . 5300 . . . . - MetThrAspProArgGluThrValP roProGlyAsnSerGlyGluGluThrIleGly AsnAspArgProGlnArgAspSerThrTh rArgLysGlnArgArgArgAspTyrArgArg AAAATGACAGACCCCAGAGAGACAGTACCAC CAGGAAACAGCGGCGAAGAGACTATCGGA . . . . . 5400 - GluAlaPheAlaTrpLeuAsnArgTh rValGluAlaIleAsnArgGluAlaValAsnHis GlyLeuArgLeuAlaLysGlnAspSerArgSerHisLysGlnArgSerSerGluSerPro GAGGCCTTCGCCTGGCTAAACAGGACAGTAG AAGCCATAAACAGAGAAGCAGTGAATCAC . . . . . . - LeuProArgGluLeuIlePheGlnValT rpGlnArgSerTrpArgTyrTrpHisAspGlu ThrProArgThrTyrPheProGlyValAl aGluValLeuGluIleLeuAla CTACCCCGAGAACTTATTTTCCAGGTGTGGCAGAGGTCCTGGAGATACTGGCATGATGAA . . . 5500 . . - GlnGlyMetSerGluSerTyrThrLysTyrArgTyrLeuCysIleIleGlnLysAlaVal CAAGGGATGTCAGAAAGTTACACAAAGTATA GATATTTGTGCATAATACAGAAAGCAGTG . . . . . . - TyrMetHisValArgLysGlyCysThrC ysLeuGlyArgGlyHisGlyProGlyGlyTrp TACATGCATGTTAGGAAAGGGTGTACTTGCC TGGGGAGGGGACATGGGCCAGGAGGGTGG . 5600 . . . . - ArgProGlyProProProProProProP roGlyLeuVal MetAlaGluAlaProThrGlu AGACCAGGGCCTCCTCCTCCTCCCCCTCCAG GTCTGGTCTAATGGCTGAAGCACCAACAG . . . . . 5700 - LeuProProValAspGlyThrProLe uArgGluProGlyAspGluTrpIleIleGluIle AGCTCCCCCCGGTGGATGGGACCCCACTGAGGGAGCCAGGGGATGAGTGGATAATAGAAA . . . . . . - LeuArgGluIleLysGluGluAlaLeuLysHisPheAspProArgLeuLeuIleAlaLeu TCTTGAGAGAAATAAAAGAAGAAGCTTTAAA GCATTTTGACCCTCGCTTGCTAATTGCTC . . . 5800 . . - MetGluThrProLeuLysAlaProGluSerSerL eu GlyLysTyrIleTyrThrArgHisGlyAspThrLeuGluGlyAlaArgGluLeuIleLys TTGGCAAATATATCTATACTAGACATGGAGA CACCCTTGAAGGCGCCAGAGAGCTCATTA . . . . . . - LysSerCysAsnGluProPheSerArgT hrSerGluGlnAspValAlaThrGlnGluLeu ValLeuGlnArgAlaLeuPheThrHisPh eArgAlaGlyCysGlyHisSerArgIleGly AAGTCCTGCAACGAGCCCTTTTCACGCACTT CAGAGCAGGATGTGGCCACTCAAGAATTG . 5900 . . . . - AlaArgGlnGlyGluGluIleLeuSerG lnLeuTyrArgProLeuGluThrCysAsnAsn GlnThrArgGlyGlyAsnProLeuSerAl aIleProThrProArgAsnMetGln GCCAGACAAGGGGAGGAAATCCTCTCTCAGC TATACCGACCCCTAGAAACATGCAATAAC . . . . . 6000 - SerCysTyrCysLysArgCysCysTyrH isCysGlnMetCysPheLeuAsnLysGlyLeu TCATGCTATTGTAAGCGATGCTGCTACCATT GTCAGATGTGTTTTCTAAACAAGGGGCTC . . . . . . - GlyIleCysTyrGluArgLysGlyArgA rgArgArgThrProLysLysThrLysThrHis MetAsnGluArgAlaAspGlu GluGlyLeuGlnArgLysLeuArgLeuIle GGGATATGTTATGAACGAAAGGGCAGACGAA GAAGGACTCCAAAGAAAACTAAGACTCAT . . . 6100 . . - ProSerProThrProAspLys ArgLeuLeuHisGlnThr MetMetAsnGlnLeuLeuIleAlaIleLeuLeuAla CCGTCTCCTACACCAGACAAGTGAGTATGAT GAATCAGCTGCTTATTGCCATTTTATTAG . . . . . . - SerAlaCysLeuValTyrCysThrGl nTyrValThrValPheTyrGlyValProThrTrp CTAGTGCTTGCTTAGTATATTGCACCCAATATGTAACTGTTTTCTATGGCGTACCCACGT . 6200 . . . . - LysAsnAlaThrIleProLeuPheCysAlaThrArgAsnArgAspThrTrpGlyThrIle GGAAAAACGCAACCATTCCCCTCTTTTGTGC AACCAGAAATAGGGATACTTGGGGAACCA . . . . . 6300 - GlnCysLeuProAspAsnAspAspTy rGlnGluIleThrLeuAsnValThrGluAlaPhe TACAGTGCTTGCCTGACAATGATGATTATCAGGAAATAACTTTGAATGTAACAGAGGCTT . . . . . . - AspAlaTrpAsnAsnThrValThrGluGlnAlaIleGluAspValTrpHisLeuPheGlu TTGATGCATGGAATAATACAGTAACAGAACA AGCAATAGAAGATGTCTGGCATCTATTCG . . . 6400 . . - ThrSerIleLysProCysValLysLe uThrProLeuCysValAlaMetLysCysSerSer AGACATCAATAAAACCATGTGTCAAACTAACACCTTTATGTGTAGCAATGAAATGCAGCA . . . . . . - ThrGluSerSerThrGlyAsnAsnThrThrSerLysSerThrSerThrThrThrThrThr GCACAGAGAGCAGCACAGGGAACAACACAAC CTCAAAGAGCACAAGCACAACCACAACCA . 6500 . . . . - ProThrAspGlnGluGlnGluIleSe rGluAspThrProCysAlaArgAlaAspAsnCys CACCCACAGACCAGGAGCAAGAGATAAGTGAGGATACTCCATGCGCACGCGCAGACAACT . . . . . 6600 - SerGlyLeuGlyGluGluGluThrIleAsnCysGlnPheAsnMetThrGlyLeuGluArg GCTCAGGATTGGGAGAGGAAGAAACGATCAA TTGCCAGTTCAATATGACAGGATTAGAAA . . . . . . - AspLysLysLysGlnTyrAsnGluTh rTrpTyrSerLysAspValValCysGluThrAsn GAGATAAGAAAAAACAGTATAATGAAACATGGTACTCAAAAGATGTGGTTTGTGAGACAA . . . 6700 . . - AsnSerThrAsnGlnThrGlnCysTyrMetAsnHisCysAsnThrSerValIleThrGlu ATAATAGCACAAATCAGACCCAGTGTTACAT GAACCATTGCAACACATCAGTCATCACAG . . . . . . - SerCysAspLysHisTyrTrpAspAl aIleArgPheArgTyrCysAlaProProGlyTyr AATCATGTGACAAGCACTATTGGGATGCTATAAGGTTTAGATACTGTGCACCACCGGGTT . 6800 . . . . - AlaLeuLeuArgCysAsnAspThrAsnTyrSerGlyPheAlaProAsnCysSerLysVal ATGCCCTATTAAGATGTAATGATACCAATTA TTCAGGCTTTGCACCCAACTGTTCTAAAG . . . . . 6900 - ValAlaSerThrCysThrArgMetMe tGluThrGlnThrSerThrTrpPheGlyPheAsn TAGTAGCTTCTACATGCACCAGGATGATGGAAACGCAAACTTCCACATGGTTTGGCTTTAA . . . . . . - GlyThrArgAlaGluAsnArgThrTy rIleTyrTrpHisGlyArgAspAsnArgThrIle ATGGCACTAGAGCAGAGAATAGAACATATATCTATTGGCATGGCAGAGATAATAGAACTA . . . 7000 . . - IleSerLeuAsnLysTyrTyrAsnLeuSerLeuHisCysLysArgProGlyAsnLysThr TCATCAGCTTAAACAAATATTATAATCTCAG TTTGCATTGTAAGAGGCCAGGGAATAAGA . . . . . . - ValLysGlnIleMetLeuMetSerGl yHisValPheHisSerHisTyrGlnProIleAsn CAGTGAAACAAATAATGCTTATGTCAGGACATGTGTTTCACTCCCACTACCAGCCGATCA . 7100 . . . . - LysArgProArgGlnAlaTrpCysTrpPheLysGlyLysTrpLysAspAlaMetGlnGlu ATAAAAGACCCAGACAAGCATGGTGCTGGTT CAAAGGCAAATGGAAAGACGCCATGCAGG . . . . . 7200 - ValLysGluThrLeuAlaLysHisPr oArgTyrArgGlyThrAsnAspThrArgAsnIle AGGTGAAGGAAACCCTTGCAAAACATCCCAGGTATAGAGGAACCAATGACACAAGGAATA . . . . . . - SerPheAlaAlaProGlyLysGlySerAspProGluValAlaTyrMetTrpThrAsnCys TTAGCTTTGCAGCGCCAGGAAAAGGCTCAGA CCCAGAAGTAGCATACATGTGGACTAACT . . . 7300 . . - ArgGlyGluPheLeuTyrCysAsnMe tThrTrpPheLeuAsnTrpIleGluAsnLysThr GCAGAGGAGAGTTTCTCTACTGCAACATGACTTGGTTCCTCAATTGGATAGAGAATAAGA . . . . . . - HisArgAsnTyrAlaProCysHisIleLysGlnIleIleAsnThrTrpHisLysValGly CACACCGCAATTATGCACCGTGCCATATAAA GCAAATAATTAACACATGGCATAAGGTAG . 7400 . . . . - ArgAsnValTyrLeuProProArgGl uGlyGluLeuSerCysAsnSerThrValThrSer GGAGAAATGTATATTTGCCTCCCAGGGAAGGGGAGCTGTCCTGCAACTCAACAGTAACCA . . . . . 7500 - IleIleHisAsnIleAspTrpGlnAsnAsnAsnGlnThrAsnIleThrPheSerAlaGlu GCATAATTGCTAACATTGACTGGCAAAACAA TAATCAGACAAACATTACCTTTAGTGCAG . . . . . . - ValAlaGluLeuTyrArgLeuGluLe uGlyAspTyrLysLeuValGluIleThrProIle AGGTGGCAGAACTATACAGATTGGAGTTGGGAGATTATAAATTGGTAGAAATAACACCAA . . . 7600 . . - GlyPheAlaProThrLysGluLysArgTyrSerSerAlaHisGlyArgHisThrArgGly TTGGCTTCGCACCTACAAAAGAAAAAGATAC TCCTCTGCTCACGGGAGACATACAAGAG . . . . . . - ValPheValLeuGlyPheLeuGlyPh eLeuAlaThrAlaGlySerAlaMetGlyAlaAla GTGTGTTCGTGCTAGGGTTCTTGGGTTTTCTCGCAACAGCAGGTTCTGCAATGGGCGCGG . 7700 . . . . - SerLeuThrValSerAlaGlnSerArgThrLeuLeuAlaGlyIleValGlnGlnGlnGln CGTCCCTGACCGTGTCGGCTCAGTCCCGGAC TTTACTGGCCGGGATAGTGCAGCAACAGC . . . . . 7800 - GlnLeuLeuAspValValLysArgGl nGlnGluLeuLeuArgLeuThrValTrpGlyThr AACAGCTGTTGGACGTGGTCAAGAGACAACAAGAACTGTTGCGACTGACCGTCTGGGGAA . . . . . . - LysAsnLeuGlnAlaArgValThrAlaIleGluLysTyrLeuGlnAspGlnAlaArgLeu CGAAAAACCTCCAGGCAAGAGTCACTGCTAT AGAGAAGTACCTACAGGACCAGGCGCGGC . . . 7900 . . - AsnSerTrpGlyCysAlaPheArgGl nValCysHisThrThrValProTrpValAsnAsp TAAATTCATGGGGATGTGCGTTTAGACAAGTCTGCCACACTACTGTACCATGGGTTAATG . . . . . . - SerLeuAlaProAspTrpAspAsnMetThrTrpGlnGluTrpGluLysGlnValArgTyr ATTCCTTAGCACCTGACTGGGACAATATGAC GTGGCAGGAATGGGAAAAACAAGTCCGCT . 8000 . . . . - LeuGluAlaAsnIleSerLysSerLe uGluGlnAlaGlnIleGlnGlnGluLysAsnMet ACCTGGAGGCAAATATCAGTAAAAGTTTAGAACAGGCACAAATTCAGCAAGAGAAAAATA . . . . . 8100 - TyrGluLeuGlnLysLeuAsnSerTrpAspIlePheGlyAsnTrpPheAspLeuThrSer TGTATGAACTACAAAAATTAAATAGCTGGGA TATTTTTGGCAATTGGTTTGACTTAACCT . . . . . . - TrpValLysTyrIleGlnTyrGlyVa lLeuIleIleValAlaValIleAlaLeuArgIle CCTGGGTCAAGTATATTCAATATGGAGTGCTTATAATAGTAGCAGTAATAGCTTTAAGAA . . . 8200 . . - ValIleTyrValValGlnMetLeuSerArgLeuArgLysGlyTyrArgProValPheSer TAGTGATATATGTAGTACAAATGTTAAGTAG GCTTAGAAAGGGCTATAGGCCTGTTTTCT . . . . . . - SerIleSerThrArgThrGlyAspSerGlnPro AsnProTyrProGlnGlyProGlyThrAlaSerGln SerProProGlyTyrIleGlnGlnIleHi sIleHisLysAspArgGlyGlnProAlaAsn CTTCCCCCCCCGGTTATATCCAACAGATCCA TATCCACAAGGACCGGGGACAGCCAGCCA . 8300 . . . . - ThrLysLysGlnLysLysThrValGluA laThrValGluThrAspThrGlyProGlyArg ArgArgAsnArgArgArgArgTrpLysGln ArgTrpArgGlnIleLeuAlaLeuAlaAsp GluGluThrGluGluAspGlyGlySerAs nGlyGlyAspArgTyrTrpProTrpProIle ACGAAGAAACAGAAGAAGACGGTGGAAGCAA CGGTGGAGACAGATACTGGCCCTGGCCGA . . . . . 8400 - SerIleTyrThrPheProAspProProA laAspSerProLeuAspGlnThrIleGlnHis AlaTyrIleHisPheLeuIleArgGlnLeu IleArgLeuLeuThrArgLeuTyrSerIle TAGCATATATACATTTCCTGATCCGCCAGCT GATTCGCCTCTTGACCAGACTATACAGCA . . . . . . - LeuGlnGlyLeuThrIleGlnGluLeu ProAspProProThrHisLeuProGluSerGln CysArgAspLeuLeuSerArgSerPheLeuThrLeuGlnLeuIleTyrGlnAsnLeuArg TCTGCAGGGACTTACTATCCAGGAGCTTCCT GACCCTCCAACTCATCTACCAGAATCTCA . . . 8500 . . - ArgLeuAlaGluThr MetGlyAlaSerGlySerLysLys AspTrpLeuArgLeuArgThrAlaPheLe uGlnTyrGlyCysGluTrpIleGlnGluAla GAGACTGGCTGAGACTTAGAACAGCCTTCTT GCAATATGGGTGCGAGTGGATCCAAGAAG . . . . . . - HisSerArgProProArgGlyLeuGlnG luArgLeuLeuArgAlaArgAlaGlyAlaCys PheGlnAlaAlaAlaArgAlaThrArgGl uThrLeuAlaGlyAlacysArgGlyLeuTrp CATTCCAGGCCGCCGCGAGGGCTACAAGAGA GACTCTTGCGGGCGCGTGCAGGGGCTTGT . 8600 . . . . - GlyGlyTyrTrpAsnGluSerGlyGlyG luTyrSerArgPheGlnGluGlySerAspArg ArgValLeuGluArgIleGlyArgGlyIl eLeuAlaValProArgArgIleArgGlnGly GCAGCGTATTGGAACGAATCGGGAGGGGAAT ACTCGCGGTTCCAAGAAGGATCACACAGG . . . . . 8700 - GluGlnLysSerProSerCysGluGlyA rgGlnTyrGlnGlnGlyAspPheMetAsnThr AlaGluIleAlaLeuLeu GAGCAGAAATCGCCCTCCTGTGAGGGACGGCAGTATCAGCAGGGAGACTTTATGAATACT . . . . . . - ProTrpLysAspProAlaAlaGluArgGluLysAsnLeuTyrArgGlnGlnAsnMetAsp CCATGGAAGGACCCAGCAGCAGAAAGGGAGA AAAATTTGTACAGGCAACAAAATATGGAT . . . 8800 . . - AspValAspSerAspAspAspAspGlnV alArgValSerValThrProLysValProLeu GATGTAGATTCAGATGATGATGACCAAGTAA GAGTTTCTGTCACACCAAAAGTACCACTA . . . . . . - ArgProMetThrHisArgLeuAlaIleA spMetSerHisLeuIleLysThrArgGlyGly AGACCAATGACACATAGATTGGCAATAGATA TGTCACATTTAATAAAAACAAGGGGGGGA . 8900 . . . . - LeuGluGlyMetPheTyrSerGluArgA rgHisLysIleLeuAsnIleTyrLeuGluLys CTGGAAGGGATGTTTTACAGTGAAAGAAGAG ATAAAATCTTAAATATATACTTAGAAAAG . . . . . 9000 - GluGluGlyIleIleAlaAspTrpGlnA snTyrThrHisGlyProGlyValArgTyrPro GAAGAAGGGATAATTGCAGATTGGCAGAACT ACACTCATGGGCCAGGAGTAAGATACCCA . . . . . . - MetPhePheGlyTrpLeuTrpLysLeuV alProValAspValProGlnGluGlyGluAsp ATGTTCTTTGGGTGGCTATGGAAGCTAGTAC CAGTAGATGTCCCACAAGAAGGGGAGGAC . . . 9100 . . - ThrGluThrHisCysLeuValHisProA laGlnThrSerLysPheAspAspProHisGly ACTGAGACTCACTGCTTAGTACATCCAGCAC AAACAAGCAAGTTTGATGACCCGCATGGG . . . . . . - GluThrLeuValTrpGluPheAspProL euLeuAlaTyrSerTyrGluAlaPheIleArg GAGACACTAGTCTGGGAGTTTGATCCCTTGC TGGCTTATAGTTACGAGGCTTTTATTCGG . 9200 . . . . - TyrProGluGluPheGlyHisLysSerG lyLeuProGluGluGluTrpLysAlaArgLeu TACCCAGAGGAATTTGGGCACAAGTCAGGCC TGCCAGAGGAAGAGTGGAAGGCGAGACTG . . . . . 9300 - LysAlaArgGlyIleProPheSer AAAGCAAGAGGAATACCATTTAGTTAAAGAC AGGAACAGCTATACTTGGTCAGGGCAGGA . . . . . . - AGTAACTAACAGAAACAGCTGAGACTGC AGGGACTTTCCAGAAGGGGCTGTAACCAAGGG . . . 9400 . . - AGGGACATGGGAGGAGCTGGTGGGGAAC GCCCTCATATTCTCTGTATAAATATACCCGCT . . . . . . - AGCTTGCATTGTACTTCGGTCGCTCTGC GGAGAGGCTGGCAGATTGAGCCCTGGGAGGTT . 9500 . . . . - CTCTCCAGCAGTAGCAGGTAGAGCCTGG GTGTTCCCTGCTAGACTCTCACCAGCACTTGG . . . . . 9600 - CCGGTGCTGGGCAGACGGCCCCACGCTT GCTTGCTTAAAAACCTCCTTAATAAAGCTGCC . . . . . . - AGTTAGAAGCA .
Example 5
Sequences of the Coding Regions for the Envelope Protein and GAG Product of the ROD HIV-2 Isolate
Through experimental analysis of the HIV-2 ROD isolate, the following sequences were identified for the, regions encoding the env and gag gene products. One of ordinary skill in the art will recognize that the numbering for both gene regions which follow begins for convenience with "1" rather than the corresponding number for its initial nucleotide as given in Example 4, above, in the context of the complete genomic sequence.
Envelope sequence - MetMetAsnGlnLeuLeuIleAlaIleLeuLeuAlaSerAlaCys ATGATGAATCAGCTGCTTATTGCCATTTTATTAGCTAGTGCTTGC . . . . - LeuValTyrCysThrGlnTyrValThrValPheTyrGlyValPro TTAGTATATTGCACCCAATATGTAACTGTTTTCTATGGCGTACCC . . . . . - ThrTrpLysAsnAlaThrIleProLeuPheCysAlaThrArgAsn ACGTGGAAAAATGCAACCATTCCCCTGTTTTGTGCAACCAGAAAT 100 . . . - ArgAspThrTrpGlyThrIleGlnCysLeuProAspAsnAspAsp AGGGATACTTGGGGAACCATACAGTGCTTGCCTGACAATGATGAT . . . . . - TyrGlnGluIleThrLeuAsnValThrGluAlaPheAspAlaTrp TATCAGGAAATAACTTTGAATGTAACAGAGGCTTTTGATGCATGG . 200 . . - AsnAsnThrValThrGluGlnAlaIleGluAspValTrpHisLeu AATAATACAGTAACAGAACAAGCAATAGAAGATGTCTGGCATCTA . . . . . - PheGluThrSerIleLysProCysValLysLeuThrProLeuCys TTCGAGACATCAATAAAACCATGTGTGAAACTAACACCTTTATGT . . 300 . - ValAlaMetLysCysSerSerThrGluSerSerThrGlyAsnAsn GTAGCAATGAAATGCAGCAGCACAGAGAGCAGCACAGGGAACAAC . . . . . - ThrThrSerLysSerThrSerThrThrThrThrThrProThrAsp ACAACCTCAAAGAGCACAAGCACAACCACAACCACACCCAGAGAC . . . 400 - GlnGluGlnGluIleSerGluAspThrProCysAlaArgAlaAsp CAGGAGCAAGAGATAAGTGAGGATACTCCATGCGCACGCGCAGAC . . . . . - AsnCysSerGlyLeuGlyGluGluGluThrIleAsnCysGlnPhe AACTGCTCAGGATTGGGAGAGGAAGAAACGATCAATTGCCAGTTC . . . . - AsnMetThrGlyLeuGluArgAspLysLysLysGlnTyrAsnGlu AATATGACAGGATTAGAAAGAGATAAGAAAAAACAGTATAATGAA 500 . . . . - ThrTrpTyrSerLysAspValValCysGluThrAsnAsnSerThr ACATGGTACTCAAAAGATGTGGTTTGTGAGACAAATAATAGCACA . . . . - AsnGlnThrGlnCysTyrMetAsnHisCysAsnThrSerValIle AATCAGACCCAGTGTTACATGAACCATTGCAACACATCAGTCATC . 600 . . . - ThrGluSerCysAspLysHisTyrTrpAspAlaIleArgPheArg ACAGAATCATGTGACAAGCACTATTGGGATGCTATAAGGTTTAGA . . . . - TyrCysAlaProProGlyTyrAlaLeuLeuArgCysAsnAspThr TACTGTGCACCACCGGGTTATGCCCTATTAAGATGTAATGATACC . . 700 . . - AsnTyrSerGlyPheAlaProAsnCyaSerLysValValAlsSer AATTATTCAGGCTTTGCACCCAACTGTTCTAAAGTAGTAGCTTCT . . . . - ThrCysThrArgMetMetGluThrGlnThrSerThrTrpPheGly ACATGCACCAGGATGATGGAAACGCAAACTTCCACATGGTTTGGC . . . 800 . - PheAsnGlyThrArgAlaGluAsnArgThrTyrIleTyrTrpHis TTTAATGGCACTAGAGCAGAGAATAGAACATATATCTATTGGCAT . . . . - GlyArgAspAsnArgThrIleIleSerLeuAsnLysTyrTyrAsn GGCAGAGATAATAGAACTATCATCAGCTTAAACAAATATTATAAT . . . . 900 - LeuSerLeuHisCysLysArgProGlyAsnLysThrValLysGln CTCAGTTTGCATTGTAAGAGGCCAGGGAATAAGACAGTGAAACAA . . . . - IleMetLeuMetSerGlyHisValPheHisSerHisTyrGlnPro ATAATGCTTATGTCAGGACATGTGTTTCACTCCCACTACCAGCCG . . . . . - IleAsnLysArgProArgGlnAlaTrpCysTrpPheLysGlyLys ATCAATAAAAGACCCAGACAAGCATGGTGCTGGTTCAAAGGCAAA 1000 . . . - TrpLysAspAlaMetGlnGluValLysThrLeuAlaLysHisPro TGGAAAGACGCCATGCAGGAGGTGAAGACCCTTGCAAAACATCCC . . . . . - ArgTyrArgGlyThrAsnAspThrArgAsaIleSerPheAlaAla AGGTATAGAGGAACCAATGACACAAGGAATATTAGCTTTGCAGCG . 1100 . . - ProGlyLysGlySerAspProGluValAlaTyrMetTrpThrAsn CCAGGAAAAGGCTCAGACCCAGAAGTAGCATACATGTGGACTAAC . . . . . - CysArgGlyGluPheLeuTyrCysAsnMetThrTrpPheLeuAsn TGCAGAGGAGAGTTTCTCTACTGCAACATGACTTGGTTCCTCAAT . . 1200 . - TrpIleGluAsnLysThrHisArgAsnTyrAlaProCysHisIle TGGATAGAGAATAAGACACACCGCAATTATGCACCGTGCCATATA . . . . . - LysGlnIleIleAsnThrTrpHisLysValGlyArgAsnValTyr AAGCAAATAATTAACACATGGCATAAGGTAGGGAGAAATGTATAT . . . 1300 - LeuProProArgGluGlyGluLeuSerCysAsnSerThrValThr TTGCCTCCCAGGGAAGGGGAGCTGTCCTGCAACTCAACAGTAACC . . . . . - SerIleIleAlaAsnIleAspTrpGlnAsnAsnAsnGlnThrAsn AGCATAATTGCTAACATTGACTGGCAAAACAATAATCAGACAAAC . . . . - IleThrPheSerAlaGluValAlaGluLeuTyrArgLeuGluLeu ATTACCTTTAGTGCAGAGGTGGCAGAACTATACAGATTGGAGTTG 1400 . . . . - GlyAspTyrLysLeuValGluIleThrProIleGlyPheAlaPro GGAGATTATAAATTGGTAGAAATAACACCAATTGGCTTCGCACCT . . . . ThrLysGluLysArgTyrSerSerAlaHisGlyArgHisThrArg ACAAAAGAAAAAAGATACTCCTCTGCTCAGGGGAGACATACAAGA . 1500 . . . - GlyValPheValLeuGlyPheLeuGlyPheLeuAlaThrAlaGly GGTGTGTTCGTGCTAGGGTTCTTGGGTTTTCTCGCAACAGCAGGT . . . . - SerAlaMetGlyAlaArgAlaSerLeuThrValSerAlaGlnSer TCTGCAATGGGCGCTCGAGCGTCCCTGACCGTGTCGGCTCAGTCC . . 1600 . . - ArgThrLeuLeuAlaGlyIleValGlnGlnGlnGlnGlnLeuLeu CGGACTTTACTGGCCGGGATAGTGCACCAACAGCAACAGCTGTTG . . . . AspValValLysArgGlnGlnGluLeuLeuArgLeuThrValTrp GACGTGGTCAAGAGACAACAAGAACTGTTGCGACTGACCGTCTGG . . . 1700 . - GlyThrLysAsnLeuGlnAlaArgValThrAlaIleGluLysTyr GGAACGAAAAACCTCCAGGCAAGAGTCACTGCTATAGAGAAGTAC . . . . - LeuGlnAspGlnAlaArgLeuAsnSerTrpGlyCysAlaPheArg CTACAGGACCAGGCGCGGCTAAATTCATGGGGATGTGCGTTTAGA . . . . 1800 - GlnValCysHisThrThrValProTrpValAsnAspSerLeuAla CAAGTCTGCCACACTACTGTACCATGGGTTAATGATTCCTTAGCA . . . . - ProAspTrpAspAsnMetThrTrpGlnGluTrpGluLysGlnVal CCTGACTGGGACAATATGACGTGGCAGGAATGGGAAAAACAAGTC . . . . . - ArgTyrLeuGluAlaAsnIleSerLysSerLeuGluGlnAlaGln CGCTACCTGGAGGCAAATATCAGTAAAAGTTTAGAACAGGCACAA 1900 . . . - IleGlnGlnGluLysAsnMetTyrGluLeuGlnLysLeuAsnSer ATTCAGCAAGAGAAAAATATGTATGAACTACAAAAATTAAATAGC . . . . . - TrpAspIlePheGlyAsnTrpPheAspLeuThrSerTrpValLys TGGGATATTTTTGGCAATTGGTTTGACTTAACCTCCTGGGTCAAG . 2000 . . - TyrIleGlnTyrGlyValLeuIleIleValAlaValIleAlaLeu TATATTCAATATGGAGTGCTTATAATAGTAGCAGTAATAGCTTTA . . . . . - ArgIleValIleTyrValValGlnMetLeuSerArgLeuArgLys AGAATAGTGATATATGTAGTACAAATGTTAAGTAGGCTTAGAAAG . . 2100 . GlyTyrArgProValPheSerSerProProGlyTyrIleGln*** GGCTATAGGCCTGTTTTCTCTTCCCCCCCCGGTTATATCCAATAG . . . . . - IleHisIleHisLysAspArgGlyGlnProAlaAsnGluGluThr ATCCATATCCACAAGGACCGGGGACAGCCAGCCAACGAAGAAACA . . . 2200 - GluGluAspGlyGlySerAsnGlyGlyAspArgTyrTrpProTrp GAAGAAGACGGTGGAAGCAACGGTGGAGACAGATACTGGCCCTGG . . . . . - ProIleAlaTyrIleHisPheLeuIleArgGlnLeuIleArgLeu GCGATAGCATATATACATTTCCTGATCCGCCAGCTGATTCGCCTC . . . . - LeuThrArgLeuTyrSerIleCysArgAspLeuLeuSerArgSer TTGACCAGACTATACAGCATCTGCAGGGACTTACTATCCAGGAGC 2300 . . . . - PheLeuThrLeuGlnLeuIleTyrGlnAsnLeuArgAspTrpLeu TTCCTGACCCTCCAACTCATCTACCAGAATCTCAGAGACTGGCTG . . . . - ArgLeuArgThrAlaPheLeuGlnTyrGlyCysGluTrpIleGln AGACTTAGAACAGCCTTCTTGCAATATGGGTGCGAGTGGATCCAA . 2400 . . . - GluAlaPheGlnAlaAlaAlaArgAlaThrArgGluThrLeuAla GAAGCATTCCAGGCCGCCGCGAGGGCTACAAGAGAGACTCTTGCG . . . . - GlyAlaCysArgGlyLeuTrpArgValLeuGluArgIleGlyArg GGCGCGTGCAGGGGCTTGTGGAGGGTATTGGAACGAATCGGGAGG . . 2500 . . - GlyIleLeuAlaValProArgArgIleArgGlnGlyAlaGluIle GGAATACTCGCGGTTCCAAGAAGGATCAGACAGGGAGCAGAAATC . . . . - AlaLeuLeu***GlyThrAlaValSerAlaGlyArgLeuTyrGlu GCCCTCCTGTGAGGGACGGCAGTATCAGCAGGGAGACTTTATGAA . . . 2600 . - TyrSerMetGluGlyProSerSerArgLysGlyGluLysPheVal TACTCCATGGAAGGACCCAGCAGCAGAAAGGGAGAAAAATTTGTA . . . . - GlnAlaThrLysTyrGly CAGGCAACAAAATATGGA . . - - MetGlyAlaArgAsnSerValLeuArgGlyLysLysAlaAspGlu ATGGGCGCGAGAAACTCCGTCTTGAGAGGGAAAAAAGCAGATGAA . . . . - LeuGluArgIleArgLeuArgProGlyGlyLysLysLysTyrArg TTAGAAAGAATCAGGTTACGGCCCGGGGGAAAGAAAAAGTACAGG . . . . . - LeuLysHisIleValTrpAlaAlaAsnLysLeuAspArgPheGly CTAAAACATATTGTGTGGGCAGCGAATAAATTGGACAGATTCGGA 100 . . . - LeuAlaGluSerLeuLeuGluSerLysGluGlyCysGluLysIle TTAGCAGAGAGCCTGTTGGAGTCAAAAGAGGGTTGTCAAAAAATT . . . . . - LeuThrValLeuAspProMetValProThrGlySerGluAsuLeu CTTACAGTTTTAGATCCAATGGTACCGACAGGTTCAGAAAATTTA . 200 . . - LysSerLeuPheAsnThrValCysValIleTrpCysIleHisAla AAAAGTCTTTTTAATACTGTCTGCGTCATTTGGTGCATACACGCA . . . . . - GluGluLysValLysAspThrGluGlyAlaLysGlnIleValArg GAAGAGAAAGTGAAAGATACTGAAGGAGCAAAACAAATAGTGCGG . . 300 . - ArgHisLeuValAlaGluThrGlyThrAlaGluLysMetProSer AGACATCTAGTGGCAGAAACAGGAACTGCAGAGAAAATGCCAACC . . . . . - ThrSerArgProThrAlaProSerSerGluLysGlyGlyAsnTyr ACAAGTAGACCAACAGCACCATCTAGCGAGAAGGGAGGAAATTAC . . . 400 - ProValGlnHisValGlyGlyAsnTyrThrHisIleProLeuSer CCAGTGCAACATGTAGGCGGCAACTACACCCATATACCGCTGAGT . . . . . - ProArgThrLeuAsnAlaTrpValLysLeuValGluGluLysLys CCCCGAACCCTAAATGCCTGGGTAAAATTAGTAGAGGAAAAAAAG . . . . - PheGlyAlaGluValValProGlyPheGlnAlaLeuSerGluGly TTCGGGGCAGAAGTAGTGCCAGGATTTCAGGCACTCTCAGAAGGC 500 . . . . - CysThrProTyrAspIleAsnGlnMetLeuAsnCysValGlyAsp TGCACGCCCTATGATATCAACCAAATGCTTAATTGTGTGGGCGAC . . . . - HisGlnAlaAlaMetGlnIleIleArgGluIleIleAsnGluGlu CATCAAGCAGCCATGCAGATAATCAGGGAGATTATCAATGAGGAA . 600 . . . - AlaAlaGluTrpAspValGlnHisProIleProGlyProLeuPro GCAGCAGAATGGGATGTGCAACATCCAATACCAGGCCCCTTACCA . . . . - AlaGlyGluLeuArgGluProArgGlySerAspIleAlaGlyThr GCGGGGCAGCTTAGAGAGCCAAGGGGATCTGACATAGCAGGGACA . . 700 . . - ThrSerThrValGluGluGlnIleGlnTrpMetPheArgProGln ACAAGCACAGTAGAAGAACAGATCCAGTGGATGTTTAGGCCACAA - AsnProValProValGlyAsnIleTyrArgArgTrpIleGlnIle AATCCTGTACCAGTAGGAAACATCTATAGAAGATGGATCCAGATA . . . 800 . - GlyLeuGlnLysCysValArgMetTyrAsnProThrAsnIleLeu GGATTGCAGAAGTGTGTCAGGATGTACAACCCGACCAACATCCTA . . . . - AspIleLysGlnGlyProLysGluProPheGlnSerTyrValAsp GACATAAAACAGGGACCAAAGGAGCCGTTCCAAAGCTATGTAGAT . . . . 900 - ArgPheTyrLysSerLeuArgAlaGluGlnThrAspProAlaVal AGATTCTACAAAAGCTTGAGGGCAGAACAAACAGATCCAGCAGTG . . . . - LysAsnTrpMetThrGlnThrLeuLeuValGlnAsnAlaAsnPro AAGAATTGGATGACCCAAACACTGCTAGTACAAAATGCCAACCCA . . . . . - AspCysLysLeuvalLeuLysGlyLeuGlyMetAsnProThrLeu GACTGTAAATTAGTGCTAAAAGGACTAGGGATGAACCCTACCTTA 1000 . . . - GluGluMetLeuThrAlaCysGlnGlyValGlyGlyProGlyGln GAAGAGATGCTGACCGCCTGTCAGGGGGTAGGTGGGCCAGGCCAG . . . . . - LysAlaArgLeuMetAlaGluAlaLeuLysGluValIleGlyPro AAAGCTAGATTAATGGCAGAGGCCCTGAAAGAGGTCATAGGACCT . 1100 . . - AlaProIleProPheAlaAlaAlaGlnGlnArgLysAlaPheLys GCCCCTATCCCATTCGCAGCAGCCCAGCAGAGAAAGGCATTTAAA . . . . . - CysTrpAsnCysGlyLysGluGlyHisSerAlaArgGlnCysArg TGCTGGAACTGTGGAAAGGAAGGGCACTCGGCAAGACAATGCCGA . . 1200 . - AlaProArgArgGlnGlyCysTrpLysCysGlyLysProGlyHis GCACCTAGAAGGCAGGGCTGCTGGAAGTGTGGTAAGCCAGGACAC . . . . . - IleMetThrAsnCysProAspArgGlnAlaGlyPheLeuGlyLeu ATCATGACAAACTGCCCAGATAGACAGGCAGGTTTTTTAGGACTG . . . 1300 - GlyProTrpGlyLysLysProArgAsnPheProValAlaGlnVal GGCCCTTGGGGAAAGAAGCCCCGCAACTTCCCCGTGGCCCAAGTT . . . . . - ProGlnGlyLeuThrProThrAlaProProValAspProAlaVal CCGCAGGGGCTGACACCAACAGCACCCCCAGTGGATCCAGCAGTG . . . . - AspLeuLeuGluLysTyrMetGlnGlnGlyLysArgGlnArgGlu GATCTACTGGAGAAATATATGCAGCAAGGGAAAAGACAGAGAGAG 1400 . . . . - GlnArgGluArgProTyrLysGluValThrGluAspLeuLeuHis CAGAGAGAGAGACCATACAAGGAAGTGACAGAGGACTTACTGCAC . . . . - LeuGluGlnGlyGluThrProTyrArgGluProProThrGluAsp CTCGAGCAGGGGGAGACACCATACAGGGAGCCACCAACAGAGGAC . 1500 . . . - LeuLeuHisLeuAsrSerLeuPheGlyLysAspGln TTGCTGCACCTCAATTCTCTCTTTGGAAAAGACCAG . . .
Example 6
Peptide Sequences Encoded By The ENV and GAG genes
The following coding regions for antigenic peptides, identified for convenience only by the nucleotide numbers of Example 5, within the env and gag gene regions are of particular interest. envl (1732-1809) - ArgValThrAlaIleGluLysTyr AGAGTCACTGCTATAGAGAAGTAC . . LeuGlnAspGlnAlaArgLeuAsnSerTrpGlyCysAlapheArg CTACAGGACCAGGCGCGGCTAAATTCATGGGGATGTGCGTTTAGA . . . 1800 GlnValCys CAAGTCTGC - env2 (1912-1983) - SerLysSerLeuGluGlnAlaGln AGTAAAAGTTTAGAACAGGCACAA . . IleGlnGlnGluLysAsnMetTyrGluLeuGlnLysLeuAsnSer ATTCAGCAAGAGAAAAATATGTATGAACTACAAAAATTAAATAGC 1940 . . . . Trp TGG - env3 (1482-1530) - ProThrLysGluLysArgTyrserserAlaHisGlyArgHisThrArg CCTACAAAAGAAAAAAGATACTCCTCTGCTCACGGGAGACATACAAGA . 1500 . . . - env4 (55-129) - CysThrGlnTyrvalThrvalPheTyrGlyvalPro TGCACCCAATATGTAACTGTTTTCTATGGCGTACCC . . . . ThrTrpLysAsnAlaThrlleproLeuPheCysAlaThr ACGTGGAAAAATGCAACCATTCCCCTGTTTTGTGCAACC 100 . . AspAsp GATGAT . TyrGlnGlulleThrLeuAsnValThrGluAlaPheAspAlaTrp TATCAGGAAATAACTTTGAATGTAACAGAGGCTTTTGATGCATGG . 200 . . AsnAsn AATAAT - env6 (274-330) - GluThrSerlleLysProCysValLysLeuThrproLeuCysGAGACATCAATAAAACCATGTGTGAAACTAACACCTTTATGT . 300 . ValAlaMetLysCys GTAGCAATGAAATGC - env7 (607-660) - AsnHisCysAsnThrSerVallle AACCATTGCAACACATCAGTCATQ 610 . . ThrGluSerCysAspLysHisTyrTrpAsp ACAGAATCATGTGACAAGCACTATTGGGAT . . . - env8 (661-720) - AlaIleArgPheArg GCTATAAGGTTTAGA TyrCysAlaProProGlyTyrAlaLeuLeuArgCysAsnAspThr TACTGTGCACCACCGGGTTATGCCCTATTAAGATGTAATGATACC . . 700 . . - env9 (997-1044) - LysArgProArgGlnAlaTrpCysTrpPheLysGlyLys AAAAGACCCAGACAAGCATGGTGCTGGTTCAAAGGCAAA 1000 . . . TrpLysAsp TGGAAAGAC - env10 (1132-1215) - LysGlySerAspProGluValAlaTyrMetTrpThrAsn AAAGGCTCAGACCCAGAAGTAGCATACATGTGGACTAAC . . . . CysArgGlyGluPheLeuTyrCysAsnMetThrTrpPheLeuAsn TGCAGAGGAGAGTTTCTCTACTGCAACATGACTTGGTTCCTCAAT . . 1200 . - envll (1237-1305) ArgAsnTyrAlaProCysHislle CGCAATTATGCACCGTGCCATATA . . . LysGlnllelleAsnThrTrpHisLysvalGlyArgAsnvalTyr AAGCAAATAATTAACACATGGCATAAGGTAGGGAGAAATGTATAT . . . 1300 - gagl (991-1053) - AspCysLysLeuValLeuLysGlyLeuGlyMetAsnproThrLeu GACTGTAAATTAGTGCTAAAAGGACTAGGGATGAACCCTACCTTA 1000 . . . GluGluMetLeuThrAla GAAGAGATGCTGACCGCC . .
Of the foregoing peptides, env1, env2, env3 and gag1 are particularly contemplated for diagnostic purposes, and env4, env5, env6, env7, env8, env9, env10 and env11 are particularly contemplated as protecting agents. These peptides have been selected in part because of their sequence homology to certain of the envelope and gag protein products of other of the retroviruses in the HIV group. For vaccinating purposes, the foregoing peptides may be coupled to a carrier protein by utilizing suitable and well known techniques to enhance the host's immune response. Adjuvants such as calcium phosphate or alum hydroxide may also be added. The foregoing peptides can be synthesized by conventional protein synthesis techniques, such as that of Merrifield.
It will be apparent to those skilled in the art that various modifications and variations can be made in the processes and products of the present invention. Thus, it is intended that the present application cover the modifications and variations of this invention provided they come within the scope of the appended claims and their equivalents. For convenience in interpreting the following claims, the following table sets forth the correspondence between codon codes and amino acids and the correspondence between three-letter and one-letter amino acid symbols. DNA COCON AMINO ACID 3 LET. AMINO ACID 1 LET.__________________________________________________________________________ : 1 \2: T C A G : T C A G : T C A G : : 1 : \3: : : : - : : T : TTT TCT TAT TGT : PRE SER TYR CYS : F S Y C : : T : C : TTC TCC TAC TGC : PRE SER TYR CYS : F S Y C : : : A : TTA TCA TAA TGA : LEU SER *** *** : L S * * : : : G : TTG TCG TAG TGG : LEU SER *** TRP : L S * W : - : : T : CTT CCT CAT CGT : LEU PRO HIS ARG : L P H R : : C : C : CTC CCC CAC CGC : LEU PRO HIS ARG : L P H R : : : A : CTA CCA CAA CGA : LEU PRO GLN ARG : L P Q R : : : G : CTG CCG CAG CGG : LEU PRG GLN ARG : L P Q R : - : : T : ATT ACT AAT AGT : ILE THR ASN SER : I T N S : : A : C : ATC ACC AAC AGC : ILE THR ASN SER : I T N S : : : A : ATA ACA AAA AGA : ILE THR LYS ARG : I T K R : : : G : ATG ACG AAG AGG : MET THR LYS ARG : M T K R : - : : T 1 GTT GCT GAT GGT : VAL ALA ASP GLY : V A D G : : G : C : GTC GCC GAC GGC : VAL ALA ASP GLY : V A D G : : : A : GTA GCA GAA GGA : VAL ALA GLU GLY : V A E G : : : G : GTG GCG GAG GGG : VAL ALA GLU GLY : V A E G__________________________________________________________________________ : -3 Letter 1 letter COOONS__________________________________________________________________________ ALAAGCT GCC GCA GCG ARGRCGT CGC CGA CGG AGA AGG ASNNAAT AAC ASPDGAT GAC CYSCTGT TGC GLNQCAA CAG GLUEGAA GAG GLYGGGT GGC CCA GGG HISHCAT CAC ILEIATT ATC ATA LEULCTT CTC CTA CTG TTA TTG LYSKAAA AAG METMATG PHEFTTT TTC PROPCCT CCC CCA CCG SERSTCT TCC TCA TCG AGT AGC THRTACT ACC ACA ACG TRPWTGG TYRYTAT TAC VALVGTT GTC GTA GTG ****TAA TAG TGA__________________________________________________________________________ | The molecular cloning and characterization of a novel human immunodeficiency virus type 2 (HIV-2), designated HIV-2 ROD , is described. A recombinant λ phage genomic library was screened with an HIV-2-specific probe to identify overlapping subgenomic clones. Fragments of these λ phage clones were subcloned into a suitable vector to reconstitute the complete HIV-2 ROD genome. The complete nucleotide sequence of this proviral clone was ascertained and the following genes and gene products identified: gag (including p16, p26, and p12), pol, vif, vpr, vpx, env, tat, rev, and nef. These gene products will be useful, inter alia, in in vitro diagnostic methods and kits for the detection of HIV-2-specific antisera. | 2 |
RELATED APPLICATIONS
This application is a divisional application of copending application Ser. No. 09/010,380, filed Jan. 21, 1998, now U.S. Pat. No. 6,129,707 incorporated herein by reference in its entirety.
BACKGROUND OF THE INVENTION
This invention generally relates to intravascular catheters, particularly catheters for use in percutaneous transluminal coronary angioplasty (PCTA) or stent delivery.
In a typical PTCA procedure a dilatation balloon catheter is advanced over a guidewire to a desired location within the patient's coronary anatomy where the balloon of the dilatation catheter is properly positioned within the stenosis to be dilated. The balloon is then inflated to a predetermined size with radiopaque liquid at relatively high pressures (generally 8-18 atmospheres) to dilate the stenosed region of the diseased artery. One or more inflations may be needed to effectively dilate the stenosis. The catheter may then be withdrawn from the stenosis or advanced further into the patient's coronary anatomy to dilate additional stenoses.
The distal tip of an intravascular catheter may be constructed to have non-traumatic characteristics to minimize damage when passing through a body lumen. A typical non-traumatic tip is formed from a short tubular member made of relatively soft polymeric material which is secured to the distal tip of the tubular distal extremity of the catheter. However, this construction does not always eliminate injury to the luminal lining. For example, the leading edge of the distal skirt of the balloon which extends radially outward can cause intimal injury even though it may be somewhat tapered. Moreover, securing a distal lip made from softer material or otherwise designed to collapse so as to avoid intimal injury, complicates the manufacturing procedure and increases its costs.
What has been needed and heretofore unavailable is a simple, inexpensive method for forming a nontraumatic distal tip. The present invention satisfies this and other needs.
SUMMARY OF THE INVENTION
This invention is directed to a distal tip construction for intraluminal catheters which has an improved non-traumatic characteristics and which is simple and inexpensive to produce.
The catheter of the invention generally has an elongated shaft with a proximal end, a distal end, a guidewire lumen extending through at least the distal portion of the catheter and a port in the distal end in fluid communication with the guidewire lumen. The elongated catheter has a tubular distal extremity which defines the guidewire lumen and which has an expanded portion with outer dimensions greater than a proximally adjacent unexpanded portion. Preferably, the tubular distal extremity tapers in the direction distal to the expanded portion to a smaller outer diameter at the distal end thereof which defines the port therein.
In one presently preferred embodiments of the invention, the catheter is a dilatation catheter having a balloon on a distal shaft section with an inner tubular member extending through and distal to the balloon which defines the guidewire lumen. The portion of the inner tubular member extending distal to the balloon is expanded in accordance with the present invention with the distal skirt of the balloon secured to an unexpanded portion of the inner tubular member proximally adjacent to the expanded portion. The distal skirt of the balloon is preferably sealingly bonded to the exterior of the unexpanded portion of the inner tubular member in a suitable manner such as by fusion or adhesive bonding. The expanded portion of the inner tubular member which extends distal to the distal skirt of the balloon preferably has outer dimensions which are essentially the same as or slightly larger than the outer dimensions of the distal skirt of the balloon so as to present a non-traumatic exterior to the interior of the body lumen in which the catheter is advanced.
The distal tubular extremity may be formed by placing it within a molding surface, such as a sheath, with interior dimensions the same as the desired dimensions of the expanded portion of the distal tubular extremity. The interior of the distal tubular extremity is then subjected to fluid pressure and the exterior to heat which causes the heated portion to soften or melt thereby expanding to the interior dimensions of the molding surface. The proximal portion of the distal tubular extremity, which is not to be expanded, may be supported exteriorly and not subjected to elevated temperatures so that it does not expand. The part of the distal tubular extremity distal to the expanded portion is likewise not expanded in a similar manner during the manufacturing procedure.
The expanded portion of the tubular distal extremity of the catheter ranges in length from about 0.1 to about 1.0 cm, preferably about 0.2 to about 0.5 cm. The overall length of the tubular distal extremity of the catheter which extends distal to the distal balloon skirt in the aforesaid presently preferred embodiment ranges from about 0.2 to about 1.5 cm, preferably about 0.3 to about 0.7 cm. The inner diameter or dimensions of the guidewire lumen extending through the expanded portion ranges from about 0.018 to about 0.035 inch (0.46-0.89 mm), preferably about 0.021 to about 0.025 inches (0.53-0.64 mm). The inner transverse dimensions of the guidewire lumen proximal to the expanded portion for a 3 mm balloon is about 0.013 to about 0.023 inches (0.33-0.58 mm), preferably about 0.016 to about 0.019 inch (0.41-0.48 mm) for a 0.014 inch (0.36 mm) guidewire. The guidewire lumen distal to the expanded portion is preferably tapered from the inner diameter of the expanded portion to transverse dimension slightly greater than the transverse dimensions of the guidewire to be passed therethrough. The wall thickness of the tubular distal extremity will vary depending upon the polymeric material from which the tubular member is made. The wall thickness of the expanded portion will usually be less than the unexpanded portion due to the expansion thereof by blowing unless the wall thickness of the portion to be expanded is initially greater than the portion which is not to be expanded.
The present invention provides an improved non-traumatic distal tip for intravascular catheters, which has gradual distal transitions in both profile and stiffness. This is particularly advantageous in balloon dilatation catheters where the distal skirt of the balloon can be secured to the unexpanded portion of the distal tubular extremity of the catheter proximal to the expanded portion so as to present a distal tip with a smooth, uniform exterior.
These and other advantages of the invention will become more apparent from the following detailed description of the invention when taken in conjunction with the accompanying exemplary drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an elevational schematic view, partially in section, of a dilatation catheter embodying features of the invention.
FIG. 2 is a transverse cross-sectional view of the catheter shown in FIG. 1 taken along the lines 2 — 2 .
FIG. 3 is an elevational schematic view of the distal portion of another alternative embodiment of the invention wherein the catheter is of a rapid exchange type dilatation catheter.
FIG. 4 schematically illustrates the forming of the distal tubular extremity of the catheter shown in FIG. 1 .
FIG. 5 illustrates the distal tip as formed in FIG. 4 .
FIG. 6 illustrates the distal tip as in FIG. 5 with the additional step of necking the most distal portion.
DETAILED DESCRIPTION OF THE INVENTION
Reference is made to FIGS. 1 and 2 which illustrate a balloon dilatation catheter 10 embodying features of the invention. Catheter 10 has an elongated shaft 11 with proximal and distal shaft sections 12 and 13 , an adapter 14 on the proximal end of the shaft and a dilatation balloon 15 on the distal shaft section spaced proximal to the distal end 16 . An inflation lumen 17 extends between the proximal end of shaft 11 and a location spaced proximal to the distal end 16 and is in fluid communication with the interior of the dilatation balloon 15 . The catheter shaft 11 is provided with an inner tubular member 18 and an outer tubular member or jacket 19 of suitable polymeric material. A guidewire receiving lumen 20 extends within both the proximal and distal shaft sections 12 and 13 . In the distal shaft section 13 , the guidewire receiving lumen 20 is defined at least in part by the inner tubular member 18 . Guidewire 21 is slidably disposed within the inner lumen 20 and extends out the port 22 in the distal end 16 .
The balloon 15 has a distal skirt 23 which is secured to an unexpanded portion of the distal extremity of the inner tubular member 18 and a proximal skirt 24 which is secured to distal end of the outer tubular member 19 . The distal portion of the inner tubular member 18 which extends beyond the distal end of the distal skirt 23 is expanded so as to have an outer diameter or dimension approximately the same as or slightly greater than the outer diameter or dimension of the distal skirt.
The outer tubular member or jacket 19 may be formed of suitable polymeric material such as high density polyethylene, a polyester such as Hytrel® (trademark of DuPont), polyetheretherketone (PEEK) or a variety other polymeric materials. For other suitable polymeric materials, see the discussions of high modulus polymeric materials for catheter shafts found in U.S. Pat. No. 5,554,121 which issued on Sep. 26, 1996 and which is incorporated herein by reference in its entirety. The balloon 15 may be formed of homopolymers or blends of nylon, polyethylene terephthalate (PET), polyethylene, ionomers such as Surlyn® (DuPont). The balloon material is usually compatible with the material of the inner tubular member 18 so that a fusion bond can be easily formed between the distal skirt of the balloon and the inner tubular member The first inner tubular member 18 may be formed of the same material as the outer tubular member 19 or a lubricious material such a fluoropolymer or a hydrophilic material, e.g. the ethylene ethyl acrylate copolymer described in copending application Ser. No. 08/279,239, filed on Jul. 22, 1994, which is incorporated herein by reference in entirety. The low friction surface of the first inner tubular member 18 defining the guidewire receiving lumen 20 facilitates the advancement of a guidewire 21 within the guidewire receiving lumen. The inner tubular member 18 may be a coextruded member so that the exterior is compatible for fusion bonding to the balloon skirt and the interior has a lubricious surface. The inner tubular member 18 typically has an outer diameter of about 0.025 inch (0.6 mm) an inner diameter of about 0.018 inch (0.46 mm).
FIG. 3 schematically illustrates another embodiment of the invention wherein the dilatation catheter 30 is provided with rapid exchange characteristics such as described in U.S. Pat. No. 5,040, (Yock), U.S. Pat. No. 4,748,982 (Horzewski et al), U.S. Pat. No. 5,496,275 (Sirhan et al) and U.S. application Ser. No. 08/183,574, filed on Jan. 18, 1994 which have been incorporated herein. The catheter 30 generally has an elongated catheter shaft 31 and an inflatable dilatation balloon 32 on the distal shaft section 33 . An inflation lumen 34 extends within the proximal shaft section 35 and the distal shaft section 33 to a location spaced proximal to the distal end of the catheter shaft 31 and is in fluid communication with the interior of the balloon 32 . A guidewire lumen 36 extends from the distal port 37 in the distal end of the catheter shaft 31 to a proximal port 38 spaced proximal, about 7 to about 45 cm, preferably about 15 to about 35 cm, from the distal end of the catheter shaft.
The distal shaft section 33 has a concentric construction with an inner tubular member 39 which defines the guidewire lumen 36 and an outer tubular member 40 which is disposed about the inner tubular member and which defines the inflation lumen 34 between the inner and outer tubular member. The proximal portion of the distal shaft section 33 is generally formed with the proximal extremity of the outer tubular member 40 which is disposed about and secured to the proximal extremity of the inner tubular member 39 and the distal extremity of the tubular member 41 which forms the proximal shaft section 35 . The proximal shaft section 35 is preferably formed of a hypotube 42 and an outer polymeric jacket 43 . The distal extremity of the hypotube 42 may be tapered as shown to facilitate entry into the interior of the interior of the outer tubular member 40 and to provide a flexible joint between the proximal and distal shaft sections. If desired the first inner tubular member 40 and the outer tubular member 42 may be bonded together and a slit (not shown) may be provided through the bonded portions of said walls to facilitate separation of the catheter 30 and a guidewire (not shown) in the manner described in U.S. Pat. No. 4,748,982 (Horzewski et al) which has been incorporated herein by reference. One or more proximal perfusion ports (not shown) can be provided in the distal section of the catheter shaft 31 proximal to the balloon 32 which are in fluid communication with the guidewire lumen 36 and one or more distal perfusion ports (not shown) can be provided in the first inner tubular member distal to the balloon which are also in fluid communication with the guidewire lumen defined by the inner tubular member to facilitate the perfusion of oxygenated blood distal to the catheter when the balloon is inflated to dilate a lesion within the arterial passageway. Such perfusion ports are disclosed in U.S. patent application Ser. No. 08/484,267, filed on Jun. 7, 1995, which is incorporated herein by reference in its entirety.
FIG. 4 schematically illustrates a method of forming the tubular distal extremity of the invention where the tubular member is indicated by reference number 50 , the distal skirt of a balloon by reference number 51 and a heating platen and molding member by reference number 52 . A mandrel 53 is fitted into the distal end of the inner tubular member 50 and a band or collar 54 is bound about the exterior of the distal end of the inner tubular member 50 so as to seal the distal end thereof. The interior of the tubular member 50 is subjected to high pressure fluid and the portion to be expanded to elevated temperature which causes the heated portion to expand outwardly, as shown in phantom, to the molding surface 55 . The most distal portion of the inner tubular member is not heated or expanded and so forms a smooth taper from the expanded portion to the smaller portion. The final distal extremity is shown in FIG. 5 . As shown in FIG. 6, the unexpanded part 56 forming the most distal portion may be necked prior to or after the expansion to form a smaller diameter port. If the materials of the tubular member 50 and the distal skirt 51 of the balloon are compatible, the distal skirt of the balloon can be bonded to the tubular member at the same time as the more distal portion of the inner tubular member is being expanded.
To the extent not described herein or in any of the U.S. patents or patent applications which have been incorporated herein by reference, the dimensions, structural details and materials of construction may follow conventional practice for intravascular catheters such as balloon dilatation catheters used in angioplasty procedures or for stent delivery and implacement.
Various changes and modification may be made to the present invention without departing from the scope of the invention. For example, the distal shaft section of the catheter proximal to the balloon could be of an extruded dual lumen construction. | An intravascular catheter of the invention has an improved distal tip with an expanded portion which has exterior transverse dimensions greater than an unexpanded portion proximally adjacent to the expanded portion. In one presently preferred embodiment the catheter has an inflatable balloon with a distal skirt which is secured to the unexpanded portion of the distal tip so as to provide an even exterior surface thereto. | 0 |
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional of co-pending application Ser. No. 09/947,491, filed on Sep. 6, 2001. This parent application is herein entirely incorporated by reference.
FIELD OF THE INVENTION
[0002] This invention relates to novel addition products of hydroxyl-protecting groups (such as isocyanates) with oxyalkylene-substituted intermediates, such as poly(oxyalkylenated) aniline compounds, for the eventual production of substituted, and substantially pure, colorants, particularly diazo and triphenylmethane derivatives, through the reaction of such intermediates with certain reactants. These new colorants exhibit improved wax and/or oil solubility and high purity, particularly due to the inability of certain impurities to deleteriously react with the protected hydroxyl groups of either the intermediate or the colorant during and/or after formation thereof. A method for producing such novel colorants through utilization of these novel substantially pure colorant intermediates is also provided.
BACKGROUND OF THE PRIOR ART
[0003] All U.S. patents cited within this specification are hereby incorporated by reference.
[0004] Wax-based and/or oil-based ink and ink-jet systems require compatible colorants therein to provide the most effective and reliable printing results. Derivatives of poly(oxyalkylenated) dyes and/or colorants are particularly desired for these end-uses because of their miscibility, high color strength characteristics, as well as ease in handling liquid colorants of this nature. The hydroxyl groups of such poly(oxyalkylenated) colorants and/or dyes are susceptible to adventitious attack by Lewis acids and bases present within the reaction medium. Unfortunately, such an attack renders the colorant unreactive, and incapable of modifications designed to tailor wax- and/or oil-solubility or compatibility. Such unreactive, residual species are generally present as impurities in the desired colorants. Such unwanted reaction products create undesirable possibilities of reduced colorant solubilities, viscosity modifications, weakening of color strengths, and other like problems, such as discussed within certain prior art references, including U.S. Pat. No. 5,782,966 to Bui et al., and U.S. Pat. No. 5,637,638 to Chandler et al., as well as European Patent Application 769,509 to Banning et al. Such references indicate the problems associated with typical prior art processes for manufacturing certain dyes (including wax-based ink types) and/or colorants. Thus, removal or, more importantly, avoidance of ways to generate these unreactive species is absolutely necessary for providing reliable and effective dyes and/or colorants for such end-use applications. These prior art references illustrate ways to tailor the desired physical properties via the reaction of isocyanate with the dyes and/or colorants themselves after formation of such compounds. Unfortunately, such a reaction modifies the colorants as long as they are reactive. It has no effect on colorants that have been rendered unreactive. Such a synthetic route would therefore always produce unwanted unreactive impurities that are detrimental to the performance of these products in the desired ink systems. A more reliable process and thus a more reliable dye and/or colorant compound is thus necessary to provide the industry with a high color strength, optimum viscosity, high purity dye and/or colorant, particularly within wax-based and/or oil-based ink applications. The prior art teachings have not provided a sufficiently consistent soluble wax-based dye and/or colorant due to these adventitious reaction problems. The costs involved in purification necessary to ensure the finished dye and/or colorant is viable and not off-quality have proven excessive enough to merit the need for even greater improvements within this technological field.
[0005] Examples of polyoxyalkylene substituted colorants include those taught within U.S. Pat. No. 5,919,839, and EP 0 896 038 A2 describe phase change, or hot melt inks utilizing the reaction product of an isocyanate (e.g., octadecyl isocyanate) and hydroxyl containing colorant to form a colored urethane wax. Other examples of such reactions include U.S. Pat. No. 5,919,846 and PCT patent Application WO 94/14902 (all describing the reaction of hydroxyl containing colorants with mono and diisocyanates). These colorants, in order to be utilized within such hot melt ink systems require high purity and complete compatibility within the wax-based ink system. The presence of electrophilic species, in this case, phthalates for example, in the urethane substituted xanthene colorants reduces the compatibility of these colorants in such wax based ink systems. U.S. Pat. No. 4,833,197 describes an offset ink using diluents, for example, mineral oils with a boiling range of 200°-350° C., and no more than 20% of aromatic components. Again, however, electrophilic phthalates present within the urethane-substituted xanthene colorants remain insoluble in these diluents, thus making these colorants unsuitable for use in these applications. Such a problem is inherent as well with other electrophiles.
[0006] Thus, even though poly(oxyalkylenated) dyes and/or colorants have only recently been made available to the wax-based ink market, the utilization of such colorants, particularly made from certain poly(oxyalkylenated) intermediates and other reactants, has still been limited due to the lack of complete compatibility in wax and/or oil based systems due to the formation of the aforementioned deleteroius electrophile-hydroxyl reaction products. There thus exists a need to improve upon this procedure and ultimately to produce a novel intermediate which provides the ability of forming highly desirable derivatized oxyalkylenated dyes and/or colorants but does not require a multi-step process in forming the intermediate alone which furthermore precludes the formation of deleterious phthalates. To date, the prior art has not accorded such an improvement within this specific area of colorant chemistry. Because of the lack of such a specific type of dye and/or colorant intermediate, the versatility and widespread use of such colorants in different types of inks and substrates has not been available. There is thus a need to provide wax-based and/or oil-based ink-jet colorants and compositions that are readily and consistently soluble due to reduction of electrophilic reaction products. To date, there have been no improvements for such wax-based dyes and/or colorants reducing the possible production of deleterious electrophile impurities thus permitting consistent use within, as one possible end-use, wax-based ink-jet inks.
OBJECTS OF THE INVENTION
[0007] Therefore, one of the objects of the invention is to provide a thoroughly wax- and/or oil-soluble urethane-substituted dye and/or colorant. Another object of this invention is to provide a synthetic route for such a dye and/or colorant wherein all reactive sites are substituted with hydroxyl-protecting groups, such as urethanes, ethers, diurethanes, and combinations thereof. Another object of the invention is to provide a specific urethane substituted aniline intermediate for the production of a urethane substituted dye and/or colorant. Still another object of the invention is to provide an intermediate that is an addition product of poly(oxyalkylene)aniline and an isocyanate for use in the manufacture of dyes and/or colorants, for instance poly(oxyalkylenated) diazo or triphenylmethane colorants. A further object of the invention is to provide an addition product of an isocyanate with a polyoxyalkylenated aniline intermediate which will alternatively form a dyestuff and/or colorant upon reaction with selected reactants and cannot be readily attacked by electrophilic groups and/or impurities within the reaction medium, and thus provides excellent yield of the desired colorant alone. Yet another object of this invention is to provide a relatively inexpensive method for producing such beneficial urethane-substituted dyes and/or colorants.
[0008] Accordingly, this invention encompasses an aniline derivative intermediate comprising at least one constituent selected from the group consisting of urethanes, ethers, diurethanes, and any combinations thereof, wherein said at least one constituent is a capped moiety further comprising from about 2 to about 200 moles oxyalkylene groups having from 2 to 18 carbon atoms, glycidol, glycidyl, and any combinations thereof, and wherein said constituent is solely bonded to any amine groups present on said aniline derivative intermediate. The term “aniline derivative” is intended to encompass any phenyl-based compound with at least one nitrogen atom bonded directly to the phenyl moiety and that does not also include a hydroxyl group bonded directly to the phenyl moiety (and thus is not an aminophenol).
[0009] Such hydroxyl-protecting groups include, but are not limited to reaction products of the terminal hydroxyls on the oxalkylene, glycidol, or glycidyl groups and compounds such as isocyanates, acid halides, acid anhydrides, diisocyanates (further reacted with an alcohol to form a diurethane), and the like, as well as mixtures thereof. Isocyanates are most preferred thereby forming urethane-based colorants after reaction between the hydroxyl and the isocyanate itself. The purpose for the presence of such groups is noted in greater detail below, but the term “hydroxyl-protecting group” or its plural form is intended to encompass any of such urethane, ether, or diurethane pendant groups present to prevent attack of the terminal hydroxyls by electrophilic species or other impurities within the reaction medium and which is not susceptible to attack itself (and thus removal from the hydroxyl moieties) by the same electrophiles and/or impurities. In such a manner, the desired colorants exhibit the characteristics desired of polymeric [poly(oxyalkylenated)] colorants without the potential problems associated with attack on such free hydroxyls.
[0010] Since the oxyalkylene groups as noted above, as well as any other potential hydroxyls present on the ring, are reactive, the reaction with a certain amount of such hydroxyl-protecting groups [e.g., isocyanates and diisocyanates (such as, without limitation, alkyl types, including octadecyl isocyanate, n-butyl isocyanate, and the like, and phenyl and/or subsituted phenyl types, including without limitation, toluene diisocyanate, and the like)] produces the desired protected pendant groups (e.g., urethane moieties) thereon. Most preferably, at least two hydroxyl-protecting groups (and thus, for example at least two urethane groups) are present. As one example, the most preferred intermediate compound encompassed within this invention conforms to the structure of Formula (I)
[0011] wherein R 1 , R 2 , R 3 , and R 4 are either the same or different and represent hydrogen, hydroxyl, halogen, such as Cl, Br, or F, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylsulfonyl, C 1 -C 4 alkylsulfamoyl, C 5 -C 6 cycloalkylsulfamoyl, nitro, cyano, carbomoyl, trifluoromethyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkanoyl, C 1 -C 4 alkylcarbamoyl, phenoxy, phen(C 1 -C 4 )alkoxy, phenylcarbamoyl, phenylsulfonyl, phenylsulfamoyl, benzoyl, or phenylazo groups, with each group optionally subsituted with halogens or C 1 -C 4 alkyl or C 1 -C 4 alkoxy groups; wherein x+y is greater than 0 and less than 4; wherein R′ is selected from the group consisting of hydrogen, C 1 -C 10 alkoxy, C 1 -C 10 polyoxyalkoxy, C 1 -C 10 alkylester, and C 1 -C 10 alkyl; wherein R″ is selected from the group consisting of hydrogen and C 1 -C 4 alkyl groups; and wherein R″′ is selected from the group selected from hydrogen, C 1 -C 24 alkyl groups, phenyl, substituted phenyl, and any combinations thereof. Preferably R′ is H, methyl, ethyl, Cl, Br or I, R″ is hydrogen, methyl, or ethyl, and R″′ is hydrogen, methyl, or ethyl. In a more preferred embodiment, the aniline derivative intermediate is substituted with methyl or ethyl, or is unsubstituted, i.e. R 1 , R 2 , R 3 , and R 4 are all H. The intermediate is prepared from aniline which is reacted with from 2 to 200 moles of at least one constituent selected from the group of oxyalkylenes having from 2 to 18 carbon atoms, glycidol, and glycidyl, and any combinations thereof, wherein said constituent is solely bonded to the amine. It should be evident to the ordinarily skilled polymeric colorant artisan that addition of specific chain lengths of such oxyalkylene monomers is imperfect and thus the number of moles present thereon such an aniline-based compound is indicative of the average number of moles added, and not the specific number. Preferably, R″′ is selected from C 1 -C 24 alkyl, more preferably from C 4 to C 18 .
[0012] Furthermore, the inventive colorants produced by the reaction of certain reactants with this specific type of intermediate include diazos, triphenylmethanes, and the like, preferably conforming with the following structures (II), (III), and (IV):
[0013] wherein for each of (II), (III), and (IV), above, R′ is selected from the group consisting of hydrogen, C 1 -C 10 alkoxy, and C 1 -C 20 alkyl; wherein R″ is selected from the group consisting of hydrogen, C 1 -C 10 alkoxy, and C 1 -C 20 alkyl; wherein R″′ is selected from the group consisting of hydrogen, C 1 -C 24 alkyl groups, phenyl, substituted phenyl, and any combinations thereof, and x is from 1 to 100; or any salts thereof (such as salts with inorganic or organic anions, including, without limitation, halides, sulfonates, hydrogen sulfonates, methylsulfates, and the like).
[0014] Such an aniline intermediate in Formula (I) is useful in producing the colorants of Formulae (II), (III), and (IV).
DETAILED DESCRIPTION OF THE INVENTION
[0015] The amino group of said aniline is di-substituted with an addition product of an isocyanate and a poly(oxyalkylene) substituent having a straight or branched polymer chain selected from oxyalkylene oxide, glycidyl, and glycidol. In one embodiment, at least one mole of the urethane-substituted aniline is reacted with phthalic anhydride or other aromatic compound having an aldehyde functionality available. A second mole of urethane substituted aniline may also be provided to form a triphenylmethane colorant. This novel intermediate has the advantage that colorants made from the intermediate is totally compatible in the wax-based and/or oil-based ink systems, and that colorants of various families, such as diazos, triphenylmethanes, methines, and the like, can be produced from this intermediate. Thus, reactants utilized to produce such novel colorants include, without limitation, diazonium salts, aminobenzaldehydes, diazotized compounds, and the like, which would be clearly appreciated by the ordinarily skilled artisan within the colorant industry (the term “colorant” is intended to encompass any compound which absorbs in the visible spectrum).
[0016] In particular, it is highly desirable to provide a method of forming an addition product of an isocyanate with a specific polyoxyalkylenated aniline intermediate. Furthermore, the aniline intermediate encompassed within this invention thus comprises from 2 to about 200 moles, preferably, from 3 to about 100, more preferably from about 3 to about 50, and most preferably from about 3 to about 10, of at least one constituent selected from the group of oxyalkylene groups having from 2 to 18 carbon atoms, alkoxy alkylester groups having from 2 to 18 carbon atoms, glycidol, and a glycidyl group wherein said constituent is solely bonded to the amine, and any free hydroxyls are reacted with isocyanate such as octadecyl isocyanate. Such a method of producing the addition product of an isocyanate with such a specific oxyalkylenated aniline intermediate is also contemplated within this invention as well. The amine constituent may reside in any position relative to other pendant groups (such as straight or branched alkyl chains, straight or branched alcohol chains, and the like) on the benzene ring (i.e., p-toluidine,, o-toluidine, m-toluidine, p-anisidine, o-anisidine, or m-anisidine); however, aniline and m-toluidine are preferred. Thus, the preferred aniline intermediate is also contemplated within this invention as is the method of making such a compound, as defined by the Formula (I), above. Such a method comprises the reaction of from 2 to 200 moles of at least one compound selected from the group consisting of an alkylene oxide having from 2 to 18 carbon atoms and glycidol with m-aniline at a temperature of from about 120 to about 250° F. The invention also covers the actual compound of Formula (I), above as well. Preferably R′ above (for both I and II) is hydrogen, C 1-4 alkoxy, or C 1-4 alkyl; most preferably R′ is hydrogen. Also, preferably R″ is methyl or ethyl (most preferably methyl), and R″ is preferably H. R″′ is selected from the group consisting of C 1 -C 24 alkyl, preferably R″ is C 12 -C 24 alkyl, most preferably R″′ is C 18 .
[0017] It is an advantage of the present invention that the urethane substituted dye and/or colorant can be design engineered to obtain desired properties for specific printing platforms and architectures. It is also an advantage, though not a requirement, of the present invention that the urethane substituted dye and/or colorant is very pure, being free of salts and other insoluble contaminants. It is another advantage of the present invention that the urethane substituted dye and/or colorant can be used in combination with other ink carrier materials to obtain ink compositions that possess excellent spectral strengths. It is still another advantage, though not a requirement, of the present invention that the urethane substituted dye and/or colorant is substantially transparent. These and other aspects, features, and advantages are obtained by the use of such inventive intermediates (such as urethane-substituted anilines) to form such substituted colorants that are suitable for use with waxes and/or oils in phase change ink jet inks and offset inks that may be employed in direct or indirect printing applications.
[0018] It has been found that the reaction of isocyanates with oxyalkylenated aniline compounds and other reactants (as discussed above), ultimately results in the formation of a dye and/or colorant substantially modified by the reaction of the nucleophilic hydroxyl groups of the intermediate and substantially free of unmodified, insoluble impurities, which are completely compatible in wax and/or oil systems. The structures (II), (III), and (IV) above are merely preferred embodiments of such a broad range of possible dyes and/or colorants.
[0019] As noted above, such novel intermediates permit production of colorants made therefrom that are substantially modified by the reaction of the nucleophilic hydroxyl groups with isocyanates. A low amount of such an unwanted electrophile-hydroxyl reaction product may be produced on the final colorant product; however, such an amount is drastically reduced in comparison with the previously followed production methods without isocyanate-capped hydroxyl moieties of the inventive intermediate. Thus, the amount of unwanted eletrophile-hydroxyl reaction product provided by the inventive method and thus found on the target dye and/or colorant is below about five to ten molar percent in total. Such an amount is thus the definition of the term “substantially pure” as well.
[0020] Such inventive substantially pure urethane-based colorants may be utilized in any number of coloring procedures, including ink, paint, print, dye, tint, and the like, applications. Thus, compositions utilized to provide colorations to various substrates, including, without limitation, cellulose-based substrates (paper, cotton fabrics, and the like), magazine-paper substrates, and the like, are preferred surfaces for coloring. Other surfaces, substrates, etc., may be contacted with the inventive colorants as well. Most preferably, however, such colorants are to be utilized in ink applications, most notably inkjet, lithographic, and offset ink operations. The offset printing process is used to print newsprint, magazines, signage, and like procedures and end-uses. In such operations, it is important to provide long-term solution stability of the colorant within the target ink solution and water resistance of the printed image from the ink composition. For inkjet inks, particularly wax-based types, heat stability of the entire ink system is of paramount importance, since the printing process comprises numerous periods of heating and cooling cycles in order for the inks to perform the desired print operation. Thus, such inks must be able to retain their color strength upon evaluation of exposure at 150° C. for prolonged and/or intermittent periods (e.g., 30 minutes or 5 minutes heated, 5 minutes cooled, 5 minutes heated, and so on, as merely examples). The color difference between an initial print and an oven-aged print is calculated using the following equation:
Δ E *=(( L* initial −L* aged ) 2 +( a* initial −a* aged ) 2 +( b* initial −b* aged ) 2 ) 1/2
[0021] wherein ΔE* represents the difference in color between the initial printed sample and the sample printed with oven aged ink. L*, a*, and b* are the color coordinates; wherein L* is a measure of the lightness and darkness of the print sample; a* is a measure of the redness or greenness of the print sample; and b* is a measure of the yellowness or blueness of the print sample. For a further discussion and explanation of this testing procedure, see Billmeyer, F. W., et al., Principles of Color Technology , 2nd Edition, pp. 62-64 and 101-04. Thus, the inks must exhibit a minimal change in color over such time (e.g., ΔE* of at most 1.5).
[0022] For offset inks, and particularly heat-set inks, generally, such compositions include alkyds as heat-set inks used primarily as pigment-wetting vehicles (although they may also improve the stability of the ink, improve the gloss of the ink on the target substrate, and affect water pick-up after contact with the desired surface). High boiling petroleum distillates are utilized as the diluent/solvent components therein within such heat-set offset ink formulations. Other additives commonly found within such offset inks are polyethylene (slip agent), organic aluminum compounds (rheology modifiers), and low molecular weight micronized hydrocarbon resins (to increase ink tack).
[0023] For lithographic inks (cold set), generally, such compositions function through penetration of the ink within the target substrate (e.g., paper, for example). Mineral oil or vegetable oils are utilized as carriers within such compositions with small amounts of varnish (typically gilsonite or hydrocarbon-based resins, as examples) added to control the lithographic properties of the ink composition, with components, such as bentonite, for example, added for rheology control.
[0024] Wax-based inkjet inks are generally solid at room temperature and subsequently heated to a temperature above its melting point and maintained at a temperature above about 150° C. wherein the composition must exhibit fluid physical properties required for inkjet printing methods. Thus, these inkjet ink composition generally comprise two component types: colorants and vehicles for the colorants. The vehicle often consists of a blend of polymers which function to control the viscosity temperature profile and balance the performance of the ink in the printhead with the performance of the ink on the target substrate surface (e.g., again, paper). Such polymers tend to be based upon fatty acids, urethanes, and natural and/or synthetic waxes.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0025] Without limiting the scope of the invention, the preferred features of the invention are hereinafter set forth.
[0026] Intermediate Synthesis
EXAMPLE 1
[0027] 100 parts of a polyoxyalkylene (with an average of 10 moles of ethylene oxide present thereon) substituted aniline intermediate were charged into a reactor vessel with 111 parts of octadecenyl isocyanate, and 2.0 parts of dibutyltindilaurate catalyst. The mixture was heated with stirring to 70° C. under a N 2 atmosphere. After 4.0 hours at 70 C an FT-IR spectrum of the product was obtained to insure all isocyanate functionality is consumed. The absence (disappearance) of a peak at about 2275 cm −1 (NCO) and the appearance (or increase in magnitude) of peaks at about 1740-1680 cm −1 and about 1540-1530 cm −1 corresponding to urethane frequencies, thereby confirm the conversion of the isocyanate to the urethane.
EXAMPLE 2
[0028] 100 parts of the polyoxyalkylene (having an ethylene oxide to propylene oxide ratio of about 1:1, and an average of about 5 moles of each alkylene oxide present thereon) substituted aniline intermediate were charged into a reactor vessel with 98 parts of octadecylisocyanate, and 2.0 parts of dibutyltindilaurate catalyst. The mixture was heated with stirring to 70° C. under a N 2 atmosphere. After 4.0 hours at 70 C an FT-IR spectrum of the product was obtained to insure all isocyanate functionality is consumed. The absence (disappearance) of a peak at about 2275 cm −1 (NCO) and the appearance (or increase in magnitude) of peaks at about 1740-1680 cm −1 and about 1540-1530 cm −1 corresponding to urethane frequencies, thereby confirm the conversion of the isocyanate to the urethane.
[0029] Colorant Production
[0030] The general methods of making the preferred inventive colorants are as follows:
EXAMPLE 3
[0031] (Diazo—Yellow)
[0032] 135 parts of 98% sulfuric acid was charged to a flask containing 452 parts of water followed by 111 parts of 3-chloroaniline and 12 parts of 2-ethylhexanol. This mixture was allowed to stir for 0.5 hr. Separately a mixture of 71.3 parts of sodium nitrite and 233 parts of water was prepared in a beaker. This was charged to the flask slowly, keeping the temperature of the contents in the flask between 0 and 5° C. After the addition is complete, the contents were allowed to stir for 2 hours while maintaining a temperature between 0 and 5° C. In a separate beaker, coupler was prepared by mixing 683 parts of the intermediate prepared in Example 1 with 683 parts of toluene. The diazonium salt in the flask is added to the coupler slowly maintaining a temperature <10° C. After the addition is complete, the mixture is allowed to stir for 1 hour. The acid is neutralized with a caustic solution, the product washed with water, and dried. A UV/VIS spectrum of the bright yellow product shows a lambda max absorbance at 425 nm in toluene, and a half height band width of 120 nm.
EXAMPLE 4
[0033] (Triphenylmethane—Blue)
[0034] 1000 parts of the intermediate from Example 1 was charged to a flask containing 66 parts of p-dimethylaminobenzaldehyde and 14 parts of urea. To this mixture was charged 90 parts of muriatic acid over a 5 minute period. This mixture was allowed to heat up to 95-105° C., and maintained at this temperature overnight. At the end of the hold period, the reaction mixture was allowed to cool to 75° C., and 120 parts of p-benzoquinone was added. The mixture was allowed to stir for 1.5 hrs maintaining a temperature of 75-85° C. The acid is neutralized with a caustic solution, the product washed with water, and dried. A UV/VIS spectrum of the bright mid range blue product shows a lambda max absorbances at 548 nm and 607 nm in toluene.
EXAMPLE 5
[0035] (Diazo—Red)
[0036] 160 parts of 98% sulfuric acid was charged to a flask containing 117 parts of water followed by 120 parts of acetic acid and 1 part of 2-ethylhexanol. 38 parts of 2-aminobenzothiazole was added slowly to allow complete mixing. This mixture was allowed to stir for 0.5 hr maintaining a temperature below 0° C. 95 parts of nitrosyl sulfuric acid was added slowly to this mixture slowly maintaining a temperature <0° C. This mixture was allowed to stir for 2.5 hours maintaining a temperature 0 and −5° C. At the end of the hold period, the diazotization is complete, and the diazo is added to a coupler prepared by mixing 167 parts of the intermediate from Example 2 and 167 parts of toluene maintaining temperature <10° C. After the addition is complete, the mixture is allowed to stir for 1 hour. The acid is neutralized with a caustic solution, the product washed with water, and dried. A UV/VIS spectrum of the the bright red product shows a lambda max absorbance at 489 nm in toluene, and a half height band width of 130 nm.
EXAMPLE 6
[0037] (Ink jet ink)
[0038] 20 parts of the yellow colorant produced in Example 3 was mixed with a color stick from Xerox for a Phaser™ 850 printer under heat (120-150° C.). The product was allowed to mix well while hot and poured into an aluminum dish. This mixture was subjected to several heating and cooling cycles to determine compatibility through these cycles. The product appeared to be completely compatible with the wax systems throughout the heating/cooling cycles.
EXAMPLE 7
[0039] (Offset based ink)
[0040] 5 parts of the blue colorant produced in Example 4 was mixed with a 98 parts of the black offset base 1K-01967 from CPS. The product was completely compatible. The final mixture was used as an ink and drawn down on paper. The image on paper is a toned black (b value of 2.89 vs 3.51 for untoned black base) and indicated that the individual components of the ink were completely compatible.
[0041] There are, of course, many alternate embodiments and modifications of the present invention which are intended to be included within the spirit and scope of the following claims. | Novel addition products of hydroxyl-protecting groups (such as isocyanates) with oxyalkylene-substituted intermediates, such as poly(oxyalkylenated) aniline compounds, for the eventual production of substituted, and substantially pure, colorants, particularly diazo and triphenylmethane derivatives, through the reaction of such intermediates with certain reactants are provided. These new colorants exhibit improved wax and/or oil solubility and high purity, particularly due to the inability of certain impurities to deleteriously react with the protected hydroxyl groups of either the intermediate or the colorant during and/or after formation thereof. A method for producing such novel colorants through utilization of these novel substantially pure colorant intermediates is also provided. | 2 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to thermal barrier coating systems for airfoils used in the turbine portions of gas turbine engines, and specifically to an improved coating arrangement for segments consisting of a plurality of airfoils.
2. Discussion of the Prior Art
Airfoils, typicallyAirfoil portions of at least some known blades and vanes, used in the turbine portions of gas turbine engines, such as jet engines, are typically made from superalloy materials. These materials are utilized because of their high temperature properties and the ability to withstand the corrosion and oxidation resulting from the combustion exhaust typically occurring in such engines. As the temperatures have been driven constantly higher, it has been necessary to not only modify the compositions of these materials, but also it has been necessary to add thermal barrier coatings and cooling channels to allow continued performance.
Typically, these airfoils operate under conditions of stress at very high temperatures, so that not only are oxidation and corrosion a concern, but fatigue, particularly low cycle fatigue, is also a concern. These stresses can be caused by the operating conditions experienced by the part, or may be inherent in the mechanical design and/or fabrication of the part and can shorten the operating life of an article. Fortunately, these conditions occur over an extended period of time and provide ample warning signs that a problem exists. Nevertheless, it is desirable to identify the sources of fatigue whenever possible, so that the problems due to fatigue can be reduced or eliminated. One effective way addressing the problem of fatigue is to reduce stresses in the part. If the stresses can be reduced below a critical threshold value, fatigue can be eliminated. However, even if the stresses cannot be reduced below the critical threshold value, any reduction in stresses can result in an increased life for the part.
Airfoils such as turbine bladesAt least some known airfoils in the hot turbine section of a jet engine have shown early signs of distress in a region near the tip of the airfoil. These blades are coated with a thermal barrier coating along the tip of the airfoil, in the region where the airfoil interfaces with the shroud assembly and along the leading edge of the airfoil from the tip of the airfoil to the base. The thermal barrier coating is applied to improve the thermal performance of the blade, allowing it to operate at higher temperatures. Because the high temperature environment and stresses resulting from it cannot be changed and will only be modified toward increasing temperatures, it would be advantageous to reduce the stresses encountered in this region of the blade to eliminate or to delay the onset of these early signs of distress.
Improvements in manufacturing technology and materials are the keys to increased performance and reduced costs for many articles. As an example, continuing and often interrelated improvements in processes and materials have resulted in major increases in the performance of aircraft gas turbine engines. The present invention is an improvement in manufacturing technology in the application of materials to bring about improved performance of airfoils in the turbine portion of a gas turbine engine.
BRIEF SUMMARY OF THE INVENTION
The present invention is an improved airfoil in which the thermal barrier coating system reduces stresses in a region of the airfoil near its tip, thereby at least extending the life of the airfoil. The thermal barrier system of the present invention can be applied to existing airfoils as a repair or it may be applied to new airfoils.
Airfoils typically, are hollow articles having outer surfaces over which flow the hot gases of combustion from the combuster combustor portion of the engine.
These outer or flow path surfaces include a leading edge, a trailing edge, a pressure side on a concave side of the airfoil extending from the leading edge to the trailing edge, and a convex side, opposite the concave side, side. The airfoil is formed integrally within a nozzle assembly that includes an outer band perimeter that includes an airfoil tip extending toward the shroud of the turbine section, and an airfoil outer band portion, and a fillet radius forming a smooth contour between the outer band portion of the perimeter and the leading edge, the trailing edge, the concave side of the airfoil and the convex side of the airfoil. High stresses exist in the region of the fillet radius due to a combination of mechanical and thermal stresses. The present invention reduces the concentration of stresses in the region of the fillet radius by extending the thermal barrier coating to include a preselected region of the flow path surface on at least one side of the airfoil surface between a trailing edge and about a midpoint between the trailing edge and the leading edge.
The thermal barrier coating is applied over at least the fillet radius and the outer band perimeter portion in this region. The thermal barrier coating extends onto the flow path surface for a sufficient distance below the fillet radius to reduce cumulative stresses resulting from a combination of mechanically-induced stresses from the fillet radius and the larger mass outer band and service-induced thermal stresses. The thermal barrier system includes a bond coat applied over the preselected region. An aluminide environmental coating is applied over the bond coat and a ceramic top coat is applied over the aluminide coating and the bond coat. This system reduces the overall stresses by reducing the thermal stresses in this region.
When the thermal barrier coating is applied as set forth by the present invention, the cumulative stresses are reduced in the area of the fillet radius, thereby providing an advantage of extending the life of the airfoil.
Another advantage of the present invention is that it may be applied to existing airfoils which are not coated in this region, without having to strip any pre-existing- thermal barrier coatings. The thermal barrier coatings may be applied to these regions of new airfoils as well. The fatigue life of either new or existing airfoils is thereby extended.
Other features and advantages of the present invention will be apparent from the following more detailed description of the preferred embodiment, taken in conjunction with the accompanying drawings which illustrate, by way of example, the principles of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is perspective of a nozzle segment in which the segment is a single casting having two airfoils;
FIG. 2 is a cross-section of a nozzle segment of FIG. 1 in which thermal barrier coating of the present invention is applied to supplement preexisting thermal barrier coating; and
FIG. 3 is a cross-section of a new nozzle segment of FIG. 1 that includes thermal barrier coating applied in accordance with the present invention.
DETAILED DESCRIPTION OF THE INVENTION
Airfoils used in the turbine portion of a jet engine are made from superalloy materials that are typically cast, and are generally hollow, the interior consisting of a labyrinth of passageways through which cooling air flows. The exterior of the airfoils generally are referred to as the flow path surfaces, since these surfaces are exposed to the hot gases of combustion which flow through the engine providing the energy for forward thrust and for powering the compression portion of the engine. Airfoils may be blades used with blade assemblies, which rotate, or vanes vane assemblies, which are fixed in position in relation to a gas turbine engine. Blades are attached to rotors through a base, thereby rotating with the rotor. The base is not considered part of the flow path surface.
Referring to FIG. 1 , which is a perspective of a nozzle segment 10 in which the segment is a single casting having two airfoils 12 . The casting may be made from any material and typically is made from a superalloy casting. The material will vary from engine to engine depending on the design and requirements, but for a high bypass turbofan (CF6) engines the high pressure turbine nozzle is typically constructed from Rene 80 , a well known superalloy. The outer band 14 has a relatively large mass compared to the airfoil body 16 .
Referring now to FIG. 2 , which is a cross-section of an existing nozzle segment of FIG. 1 that includes thermal barrier coating applied in accordance with the present invention, the airfoil body 16 is comprised of a leading edge 20 , a trailing edge 22 , a concave side (not shown) extending between the leading edge 20 and the trailing edge 22 on one side of the airfoil and a convex side 26 extending between the leading edge and the trailing edge. The outer band 14 that includes tips 28 is connected to the airfoil body 16 by a smooth fillet radius 30 . The base 32 of the nozzle segment is connected to airfoil body 16 opposite tips 28 . In prior art embodiments, a thermal barrier coating comprised of a bond coat was applied to tips 28 and outer band 14 and terminating in the vicinity of or on fillet radius 30 . The bond coat was also applied to the leading edge 20 from the outer band 14 to base 32 and to a line 34 approximately bisecting the airfoil as indicated by the hatched area of FIG. 2. A thermal barrier coating, typically yttrium-stabilized zirconia (YSZ) was applied over the bond coat to a thickness of 0.012-0.015 inches. Some overspray of the YSZ was permitted in the area between line lines 34 and 36 . However, the areas not requiring YSZ were usually masked, resulting in a sharp transition between the regions having the thermal barrier coating and adjacent regions.
Because of the differences in mass between outer band 14 and body 16 , a certain amount of stresses are introduced to blades airfoils at the juncture simply of the outer band and the airfoil body as a matter of thermal stresses resulting from heat transfer from a large mass to a much smaller mass. Additive to these stresses are the mechanical stresses due to the effects of the transition radius 30 . Finally, additional stresses resulted from the effects of the termination of the thermal barrier coating (TBC) in the region or the transition radius.
The present invention reduces these stresses from the effects of terminating the thermal coating in the region of the transition radius by extending the coating below radius 30 for a distance sufficient to reduce the thermal stresses in the region of radius 30 resulting from the abrupt termination of the TBC in the region of radius 30 , thereby reducing the overall accumulation of stresses in this region. This distance is indicated by d in FIG. 2 . It is preferred that this distance d extend from the fillet radius in the direction of the base such that at least about 20% of the span between the radius and the base is coated. It is preferred that d be at least about 0.5″ and preferably in the range of 0.5″ to 0.6″ for an airfoil such as the one found on the CF6 engine, but larger or smaller values are acceptable as long as the stresses resulting from the transition are lowered. Since nozzle segment 10 is comprised of two airfoils 12 , the application of the bond coat and TBC is limited by the ability of the spray nozzles used for their applications to effectively apply coating between the airfoils 12 . Thus, the TBC is applied to at least a portion of body 16 from line 36 bisecting the airfoil to the trailing edge for a distance d so that the thermal barrier coating applied to the body blends smoothly with the preexisting thermal barrier coating covering the leading edge region so that the TBC is extended from the line bisecting the airfoil toward the trailing edge. For airfoils such as those found in a CF6 application, this coating will extend from the leading edge region toward the trailing edge about at least another 0.9″. Preferably, the TBC is applied to both sides of each airfoil, but the ability of the nozzle to apply material may limit the application of material to the portions of the airfoils which face each other. The bond coat and the ceramic top coat are both applied using air plasma spray and line-of-sight application techniques. In addition, the portion of the trailing edge on the concave or pressure side includes cooling holes. Because it is unacceptable to have these holes adversely impacted by coating, it is necessary to mask these holes to prevent blockage by the TBC. This is an acceptable compromise since the cooling film resulting from the air flow assists in keeping this region cool.
While the airfoils may be masked so that a TBC may be applied to full thickness, it is preferred that the TBC be tapered from full thickness, 0.012-015″ 0.012-0.015″ at radius 30 to about 0.002-0.005 inches at a preferred distance d of 0.5-0.6″. Thus, assuming a linear taper, the preferred slope of the TBC thickness is in the range of about 0.020-0.150 in./in. and most preferably 0.021-0.140 in./in. This further reduces the possibility of thermally-induced stresses in the vicinity of the termination of the TBC.
The thermal barrier coating system of the present invention is also applied in a manner somewhat different than the prior art thermal barrier coating systems. First, the bond coat, a MCrAlY(X) where M is at least one element selected from the group consisting of Ni, Co and Fe and X is at least one element selected from the group consisting of Ti, Ta, Ru, Pt, Si, B, C, Hf, and Zr is applied by an air plasma spray process. The segment is then aluminided using a typical vapor phase aluminiding procedure. Finally, a the ceramic topcoat, 7% Yttria-Stabilized Zirconia (7YSZ) is applied over the bond coat in the region set forth above by air plasma spraying, which is an improvement over the low pressure plasma spray methods previously used to apply ceramic topcoats.
Referring now to FIGS. 2 and 3 , a cross-section of a new nozzle segment of FIG. 1 that includes thermal barrier coating applied in accordance with the present invention is depicted. All that has been said above for the nozzle segment of FIG. 2 is also applicable to the nozzle segment of FIG. 3 , except for the following. When the current invention is applied to a new nozzle segment, it is not necessary to apply the TBC to the leading edge from radius 30 to base 32 and back to line 34 bisecting airfoil body 16 . The present invention contemplates applying the TBC by the methods set forth above to the airfoil along a band from the leading edge 120 to at least about ⅔ of the distance to the trailing edge as indicated by line 150 spanning the airfoil on the concave side and to at least about ⅓ of the distance from the leading edge 120 as indicated by line 152 spanning the airfoil. , and for a distance d below radius 30 sufficient to reduce the cumulative stress below the fillet radius toward the base from a combination of mechanically-induced stresses resulting from geometric considerations and service-induced stresses. In a preferred embodiment, for airfoils such as found in a CF6 engine, the band from the leading edge to the training trailing edge extends for at least about 1.5 inches and preferably for at least about 1.8 inches. Once again, the preferred distance “d”, defining the width of the band for applications such as found in the CF6 is at least about 0.5″, an and most preferably about 0.5-0.6″, below radius 30 . , although this distance will vary among designs and service conditions encountered by such designs. This minimizes the amount of TBC that must be applied to the airfoils, providing the additional advantages of reduced weight, reduced processing time and reduces reduced cost.
The TBC wrap of the present invention is a new concept for high pressure turbine applications. The use of this wrap as set forth above, by extending the TBC below fillet region 30 and onto the flow path surfaces of the airfoil body will result in decreased metal temperatures, a more balanced thermal design and reduced peak stresses. Whereas the prior art airfoil design experienced a temperature gradient of about 80-100° F. over a distance of about ¼″, the present invention lowers the thermal gradient to about 50-80° F. over a distance of about ½″. This decrease is expected to result in at least a 50% improvement in LCF life, which is a conservative estimate. Along with lower stresses and lower temperatures in this region, there will be reduced incidents of cracking and burning.
Although the present invention has been described in connection with specific examples and embodiments, those skilled in the art will recognize that the present invention is capable of other variations and modifications within its scope. These examples and embodiments are intended as typical of. of, rather than in any way limiting on, the scope of the present invention as presented in the appended claims. | An airfoil having extended life due to reduction in stresses. The stresses are reduced by extending the thermal barrier coating below the radius between the outer band perimeter and the inner flow path surfaces and tapering the coating thickness. This additional tapered thermal barrier coating reduces the temperature gradient across a region already having high mechanical stresses resulting from geometric considerations thereby lowering thermally-induced stresses so that low cycle fatigue life is improved. | 2 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to surgical instruments and, more particularly, to endoscopic surgical instruments useful to perform endoscopic discectomy procedures and other minimally invasive spinal procedures.
2. Description of the Related Art
Back pain is a common affliction affecting millions of people. In many instances, back pain is caused by a herniated intervertebral disc. Intervertebral discs are generally cylindrical-shaped structures corresponding to the margins of the adjacent vertebrae. An outer ring known as the annulus fibrosus composed of concentric layers of fibrous tissue and fibrocartilage surrounds a cartilage-like core known as the nucleus pulposus. When an intervertebral disc is herniated, the softer nucleus projects through a torn portion of the annulus, creating a bulge which extends beyond the intervertebral foramen. As a result of the bulging disc, various spinal nerves may be compressed, causing pain or numbness.
Various procedures are used to treat herniated intervertebral discs. In mild disc herniation, pressure on adjacent nerves is lessened through non-surgical techniques. Such techniques include drugs (analgesics, anti-inflammatory drugs, muscle relaxants), physical therapy, and rest. If these non-surgical approaches are not successful, surgical intervention is necessary. Various surgical procedures have been developed to remove at least a portion of the herniated disc. Such procedures include laminotomies, laminectomies, and percutaneous discectomy.
In laminotomy (also referred to as interlaminar exploration), a posterior approach is used to access the spine through a longitudinal incision. Small amounts of the bony spinal lamina are removed, allowing access to, and removal of, portions of the herniated nucleus pulposus.
Laminectomy is a surgical procedure which, like laminotomy, uses a posterior approach to the herniated disc. In laminectomy, a larger portion of the spinal lamina or laminae are removed to access and remove portions of a herniated disc nucleus. Because both laminotomy and laminectomy require removal of bone and retraction of nerves and muscles, hospitalization and recuperation periods are lengthy. Additionally, removal of bone may lead to future spinal instability.
To minimize the need to remove portions of the vertebrae, other approaches to the herniated disc have been used. In particular, percutaneous discectomy employs a postero-lateral approach. Instruments are inserted through a cannula inserted through the patient's side. The disc annulus is pierced and the herniated nucleus is mechanically disintegrated, the pieces being removed through suction. This technique is shown for example in U.S. Pat. Nos. 4,545,374, 5,242,439 and RE 33,258.
Endoscopic surgery involves incising through body walls via small incisions, generally by use of a trocar having a obturator with a sharp tip removably positioned in a cannula. After penetration, the obturator is removed leaving the cannula positioned in the body for reception of a camera or endoscope to transmit images to a remote TV monitor. Specialized instruments such as forceps, cutters, and applicators are inserted through other trocar sites for performing the surgical procedure while being viewed by the surgeon on the monitor. With the advent of endoscopic surgery and the recognition of its advantages over open procedures in reducing costs by shortening the patient's hospital stay and time of recovery so the patient can resume normal activity sooner, the industry has been viewing endoscopic discectomy as an alternative to the techniques and surgical methods described above. However, to date, the need exists for endoscopic instrumentation to properly and atraumatically improve access to the disc to facilitate removal for successful performance of endoscopic discectomy. The need also exists for improved endoscopic instrumentation to clear a path for removal of the disc as well as to excise the disc.
U.S. Pat. No. 5,195,541 discloses a method for performing lumbar discectomy involving inserting a sleeve having an endoscope receiving means, a laser fiber receiving means and a suction and irrigation channel means. This device, however, is of relatively large diameter because it must accommodate a variety of surgical instruments and therefore may obstruct the surgeon's view (on the TV monitor) and provide limited access to the disc.
There is a need in the art for improved surgical instrumentation which facilitates minimally invasive surgical techniques for anteriorly accessing the herniated disc. The instrumentation and techniques should improve both access to and removal of the disc and permit the surgeon to endoscopically remove any desired amount of disc material with minimal interference to spinal nerves and adjacent back muscles. Such instrumentation and techniques would permit the surgical alleviation of back pain while providing the benefits attendant endoscopic/laparoscopic surgery, namely avoiding large incisions and long periods of hospital stay and patient recovery.
Such instrumentation could also advantageously be used for aiding other minimally invasive surgical spinal procedures such as spinal fusion.
SUMMARY OF THE INVENTION
The present invention provides endoscopic instrumentation and surgical techniques useful for accessing and removing at least a portion of an intervertebral disc. Instrumentation in accordance with the present invention include tissue spreaders and cutting instruments. In particular, the tissue spreading instruments include instruments for spreading pre-sacral tissue such as fascia. Other tissue spreading instruments are especially designed for spreading adjacent vertebrae to facilitate access to the intervertebral disc or for spreading the vertebrae for spinal fusion or other spinal procedures. Endoscopic cutting instruments deliver a cutting blade in a sheathed position to the site of the disc nucleus followed by deployment to remove portions of the disc nucleus.
More particularly an endoscopic surgical instrument for spreading vertebrae is provided which comprises a handle portion including an actuation member, an elongated endoscopic section extending distally from the handle portion and defining a longitudinal axis of the instrument, an actuation mechanism at least partially housed within the endoscopic section and movable in response to movement of the actuation member, and a vertebrae spreading mechanism operatively associated with a distal end portion of said endoscopic section and deployable between closed and open positions by the actuation mechanism in response to movement of the actuation member. The vertebrae spreading mechanism includes first and second vertebrae spreading arm members which are cammed by the actuation mechanism and deployable in a transverse direction with respect to the longitudinal axis of the instrument in response to movement of the actuation member such that said first and second arm members remain substantially parallel to the longitudinal axis of the instrument during deployment.
In an alternate embodiment, a drive chain is positioned between the actuation member and a threaded driving member for rotating the driving member to pivot the vertebrae spreading arm members between the open and closed positions.
The present invention may also provide an endoscopic surgical instrument for cutting tissue which comprises a handle portion including an actuation member and elongated endoscopic portion extending distally from the handle portion. An actuation rod is longitudinally reciprocable within the endoscopic portion and operatively associated with the actuation member. A cutting member is operatively associated with the actuation rod and is movable by the actuation member between a sheathed position within the endoscopic portion and a deployed position in which at least a portion of the cutting member extends distally from the endoscopic portion.
An endoscopic surgical instrument for spreading tissue may also be provided which comprises a handle portion and an elongated endoscopic section extending from the handle portion and having a proximal and distal portion and a longitudinal axis. A resilient tissue spreading mechanism extending from the distal portion of the endoscopic section and the tissue spreading mechanism is removably mounted to the endoscopic section and is spring biased in an open position.
A gaseous sealing member may be disposed within the endoscopic section of these instruments.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of an endoscopic surgical instrument for positioning a tissue spreading element according to the present invention.
FIG. 1A is a perspective view of the distal end of the instrument of FIG. 1 showing the spreading element in the deployed position.
FIG. 2 is a perspective view with parts separated of the surgical instrument of FIG. 1.
FIG. 3 is a side cross-sectional view taken along lines 3--3 of FIG. 1 illustrating the handle portion of the instrument before deployment of the spreading element.
FIG. 4 is a side cross-sectional view taken along lines 4--4 of FIG. 1 illustrating the spreading element within the distal end of the instrument.
FIG. 5 is a side cross-sectional view illustrating the handle portion of the instrument of FIG. 1 as the spreading element is deployed.
FIG. 6 is a side cross-sectional view illustrating the distal end of the instrument of FIG. 1 with the spreading element deployed.
FIG. 6A is a cross-sectional view taken along lines 6A--6A of FIG. 6 illustrating the spreading element spreading tissue.
FIG. 7 is a perspective view of a first embodiment of an endoscopic surgical instrument for spreading vertebrae according to the present invention.
FIG. 7A is a perspective view of the distal end of FIG. 7 illustrating the vertebrae spreading elements in a deployed position.
FIG. 8 is a side cross-sectional view taken along lines 8--8 of FIG. 7 illustrating the handle portion of the instrument before deployment of the vertebrae spreading elements.
FIG. 9 is a side cross-sectional view taken along lines 9--9 of FIG. 7 illustrating the vertebrae spreading elements in the non-deployed position.
FIG. 10 is a cross-sectional view taken along lines 10--10 of FIG. 9.
FIG. 11 is a side cross-sectional view taken along lines 11--11 of FIG. 7A illustrating the vertebrae spreading elements in the deployed position.
FIG. 12 is a cross-sectional view taken along lines 12--12 of FIG. 11.
FIG. 13 is a perspective view with parts separated of the vertebrae spreading portion of the instrument of FIG. 7.
FIG. 14 is a perspective view of an alternative embodiment of an endoscopic surgical instrument for spreading vertebrae according to the present invention.
FIG. 14A is a perspective view of the distal end of the instrument of FIG. 14 showing the vertebrae spreading arms in an open (deployed) position.
FIG. 15 is a side cross-sectional view of the surgical instrument taken along lines 15--15 of FIG. 14 with the vertebrae spreading arms in the non-deployed position.
FIG. 16 is a top plan cross-sectional view of the surgical instrument taken along lines 16--16 of FIG. 15 showing the vertebrae spreading arms in the non-deployed position.
FIG. 17 is a side cross-sectional view of the distal vertebrae spreading portion of the surgical instrument of FIG. 14 with the vertebrae spreading arms in an open (deployed) position.
FIG. 18 is a perspective view with parts separated of the vertebrae spreading portion of the surgical instrument of FIG. 14.
FIG. 19 is a perspective view of another alternate embodiment of an endoscopic surgical instrument for spreading vertebrae according to the present invention.
FIG. 19A is an enlarged perspective view of the distal end of the surgical instrument of FIG. 19 showing the vertebrae spreading elements in a deployed position.
FIG. 20 is a perspective view with the parts separated of the surgical instrument of FIG. 19.
FIG. 21 is a side cross-sectional view taken along lines 21--21 of FIG. 19 showing the handle portion of the surgical instrument.
FIG. 22 is a side cross-sectional view taken along lines 22--22 of FIG. 19 showing the vertebrae spreading elements in a closed (non-deployed) position.
FIG. 23 is a side cross-sectional view taken along lines 23--23 of FIG. 19A showing the vertebrae spreading elements of the surgical instrument in a deployed position.
FIG. 23A is a perspective view of an alternate structure for retaining the vertebrae spreading elements of FIG. 22.
FIG. 24 is a perspective view of an endoscopic surgical instrument for spreading tissue according to another embodiment of the present invention.
FIG. 24A is an enlarged perspective view of the distal end of the endoscopic surgical instrument of FIG. 24 showing the tissue spreading members in an open (deployed) position.
FIG. 25 is a side cross-sectional view taken along lines 25--25 of FIG. 24 illustrating the handle portion of the endoscopic surgical instrument.
FIG. 26 is a side cross-sectional view taken along lines 26--26 of FIG. 24 illustrating the tissue spreading portion of the endoscopic surgical instrument in the non-deployed position.
FIG. 26A is a cross-sectional view taken along lines 26A--26A of FIG. 26.
FIG. 27 is a perspective view with parts separated of the distal end of the endoscopic surgical instrument of FIG. 24.
FIG. 28 is a perspective view of an endoscopic surgical cutting instrument according to the present invention.
FIG. 28A is an enlarged perspective view of the distal end of the endoscopic surgical cutting instrument of FIG. 28 showing the knife blade in an extended position.
FIG. 29 is a perspective view with parts separated of the endoscopic surgical cutting instrument of FIG. 28.
FIG. 30 is an enlarged top plan view of the handle portion of the endoscopic surgical cutting instrument of FIG. 28.
FIG. 31 is a side cross-sectional view of the surgical instrument of FIG. 28 taken along lines 31--31 of FIG. 30.
FIG. 32 is a side cross-sectional view of the distal cutting portion of the endoscopic cutting instrument taken along lines 32--32 of FIG. 28A showing the knife blade in an extended position.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
A. Instrumentation
Turning now to the drawings in detail in which like reference numerals identify similar or identical elements throughout the several views, FIG. 1 depicts an endoscopic surgical instrument 10 which may be used as a tissue spreader and particularly as a fascia spreader during an endoscopic discectomy procedure. In describing the surgical instruments of the present invention, the term "proximal" refers to a direction of the instrument away from the patient and towards the user while the term "distal" refers to a direction of the instrument towards the patient and away from the user.
Surgical instrument 10 includes a handle portion 20 having an actuating member 32 at a proximal end and an elongated endoscopic portion 40 extending from a distal end. Supported at a distal end of endoscopic portion 40 is tissue spreading element housing member 60 which houses tissue spreading element 50, shown in FIG. 1A.
As seen in FIG. 2, the handle portion 20 of instrument 10 includes half-sections 22 and 24 having grip-enhancing knurled outer surfaces 23 and 25, respectively. Radially inwardly projecting pins 29 engage corresponding apertures 21 to ensure proper alignment of the handle half-sections 22, 24. When assembled, half sections 22 and 24 define a stepped axial bore 26 which houses the actuation assembly 30.
Referring now to FIGS. 2, 3, and 5, actuation assembly 30 includes a threadably advanceable driving member 36 and an actuating member 32 comprising a rotatable knob having a stepped cylindrical portion 33 extending into axial bore 26 of handle portion 20. Cylindrical portion 33 defines a bore 34 for receiving a stepped cylindrical threaded insert member 35. Rotation of actuating member 32 produces corresponding rotation of insert member 35.
The driving member 36 comprises an elongated threaded body portion 39 which engages threaded insert member 35. At its distal end, driving member 36 includes an axial bore which receives an actuation rod member 37 for positioning tissue spreading element 50. A pair of longitudinal guide slots 38 extend laterally along threaded body 39 of driving member 36. Guide slots 38 cooperatively engage guide pins 27 and 28 which project laterally inward from handle half-sections 22 and 24. The interaction of guide pins 27 and 28 with guide slots 38 permits axial reciprocal motion of driving member 36 and actuation rod 37 while prohibiting rotational motion.
Referring again to FIG. 2, to ensure proper axial alignment of actuation mechanism 30 within the handle and to ensure low friction rotary motion and ability to carry thrust loads, thrust bearing members 15 and bearing sleeve 17 are provided. Thrust bearing member 15 are positioned on both sides of alignment bearing sleeve 17 and the assembly is welded to the distal end of cylindrical portion 33.
The endoscopic portion 40 of surgical instrument 10 includes an elongated, substantially cylindrical member 42. Cylindrical member 42 houses actuation rod 37. A gaseous seal 43 is positioned within cylindrical member 42 to prevent passage of insufflation gas through the surgical instrument. The gaseous seal is provided with a central aperture to permit longitudinal reciprocal motion of actuating rod 37 therethrough. Although gaseous seal 43 is depicted as a gasket-like element which may be fabricated from, e.g., an elastomeric material, it will be appreciated by those skilled in the art that other gaseous seals, e.g., silicone grease, may be used.
A further alignment member or bushing 44 may be provided with the endoscopic portion 40 of the surgical instrument. Alignment member 44 ensures proper positioning and axial movement of the actuating rod 37 within cylindrical member 42.
Referring now to FIGS. 2, 4, and 6, extending from the distal end of cylindrical member 42 is housing 60. Housing 60 includes an elongated cylindrical section 62 which tapers to a narrowed region 64 at its proximal end. Region 64 is configured to provide an interference fit with the distal end of cylindrical member 42 for connecting housing 60 to the endoscopic section of the instrument. Within housing 60, actuating rod 37 terminates in a connector 66. Connector 66 includes bore 67 (FIG. 4) for receiving actuating rod 37 at its proximal end and cylindrical projection 68 at its distal end for removably engaging tissue spreading element 50. Alternatively, rod 37 and connector 66 with projection 68 can be formed as one piece.
Tissue spreading element 50 comprises a torsion spring having resilient tissue spreading arms 54 and 56 extending outwardly from coil portion 52 and terminating in curved hooks 55 and 57. The hooks 55 and 57 curve outwardly away from the respective arms 54 and 56 to facilitate spreading of tissue. Hooks 55 and 57 are offset from one another to prevent entanglement when in the closed position. Tissue spreading elements 54,56 are preferably composed of stainless steel and are biased to a normally open position, as shown in FIGS. 2 and 4. When positioned within housing 60, arms 54 and 56 are compressed radially inwardly as shown in FIG. 4, with hook 55 slightly rearward of hook 57. Arms 54 and 56 are bent radially inwardly in region 54a, 56a to prevent premature opening of the spring as it emerges from the housing. That is, as tissue spreading element 50 initially emerges from housing 60, tissue spreading arms 54 and 56 do not open as regions 54b, 56b are still in abutment with the inner wall of housing 60. When bent portions 54a and 56a (and regions 54b, 56b) are distal of housing 60, tissue spreading arms 54, 56 spread (spring) open to their normally open position. Tissue spreading element 54 also includes a bent portion 52a so that the remaining portions of element 54 lie in the same plane as element 56. This is more clearly shown in FIG. 6a. This symmetrical arrangement provides stability as well as facilitates forming a more uniform opening in the tissue as the tissue portions are spread apart by elements 54, 56.
Coil 52 of the tissue spreading element defines a cylindrical aperture 53 (FIG. 2) configured to releasably receive cylindrical projection 68 of connector 66. When tissue spreading element 50 is deployed, the user can slide connector 66 from within the coil interior and remove surgical instrument 10. Thus, arms 52 and 54 can be left in an open position in the patient's body. At a later time during the surgical procedure, the endoscopic portion can be re-inserted and projection 68 can be inserted into the opening in coil portion 52 to re-engage and retrieve tissue spreading element 50. Actuation member 32 can then be rotated to draw tissue spreading element 50 rearwardly into housing 60 so that arms 54 and 56 are cammed closed by the housing 60, and the entire instrument can be removed.
FIGS. 24-27 illustrates an alternate embodiment a surgical instrument 500 according to the present invention especially useful as a soft tissue spreader and, more particularly, as a fascia spreader. Instrument 500 includes handle portion 520, elongated endoscopic portion 540, and tissue spreading member 560.
As shown in FIG. 25, handle portion 520 includes rotatable portion 522 having threaded interior 523. A driving member 536 includes a threaded body portion 539 which, at its proximal end, engages interior 523. At its distal end, driving member 536 terminates in an actuation rod member 537 coaxially positioned within endoscopic portion 540. Extending laterally along threaded body portion 539 of driving member 536 is a pair of longitudinal guide slots 538 which cooperatively engage guide pin 527 laterally through the handle portion 520, crossing the longitudinal axis of the instrument. The interaction of guide pins 527 with guide slots 538 permits axial reciprocal motion of driving member 536 and actuation rod 537 while prohibiting rotational motion.
Referring to FIGS. 26 and 27, supported at a distal end of actuation rod 537 is tissue spreading member 560. Tissue spreading members 560 comprises two pairs of arms 562 formed by cutting a channel 563 in a sheet of resilient material. In one embodiment, the resilient material can be a shape memory alloy such as Tinel™, available from Raychem Corporation, Menlo Park, Calif. Clearly, other resilient materials can be utilized. The channel 563 in each spreading member 560 progressively decreases in width from the distal to the proximal end to enable the arms to be spread by pin 556 as described below. Each of the four tissue spreading arms 562 terminates in a blunt tip portion 565 configured and dimensioned to atraumatically engage tissue. Tissue spreading members 560 are affixed to the distal end of the actuation rod 537 through fastener 564 passing through apertures 570 and through aperture 535 formed in actuation rod extension 534, best seen in FIGS. 26 and 27.
To maintain axial alignment and ease of axial movement of tissue spreading member 560, insert 550 is provided at the distal end of endoscopic portion 540. Insert 550 is a cap having a narrow longitudinal axial aperture 552 for accommodating the tissue spreading member 560 and is positioned distal of guide pin 556. In use, rotation of handle portion 520 slides actuation rod member 537 and attached tissue spreading element 500 longitudinally. As tissue spreading element 560 slides distally, channel 563 passes over fixed guide pin 556 to spread arms 562 radially outwardly due to the decreasing width of the channel 563. To retract arms 562, handle portion is rotated in the opposite direction to slide arms 562 proximally within endoscopic portion 540. When deployed, the upper arms 562 spread upwardly and outwardly and the lower arms 562 spread downwardly and outwardly, thereby spreading the tissue in these directions to create a large opening. The opening created can be substantially rectangular in configuration as shown for example in FIG. 24a.
FIGS. 7-23 illustrate several embodiments of surgical instruments useful as a tissue spreader and, more particularly, as a vertebrae spreader according to the invention. The vertebrae spreading elements are composed of a substantially rigid material such as stainless steel or rigid polymer. These endoscopic vertebrae can include a gaseous seal such as an 0-ring or silicone grease to prevent the egress of gas through the instrument. Referring first to the embodiments of FIGS. 7-13 and more particularly to Figs. 7 and 7A, surgical instrument 100 includes a handle portion 120 having an actuating member 132 at a proximal end and an elongated, substantially cylindrical endoscopic portion 140 extending from a distal end. Surgical instrument 100 terminates in atraumatic tip 144. Proximal to tip 144 is vertebrae spreading mechanism 150. Vertebrae spreading mechanism 150 includes a pair of spreading members 152, shown in a deployed position in FIG. 7A, especially useful for spreading vertebrae during an endoscopic discectomy procedure.
As seen in FIG. 8, actuating member 132 comprises a rotatable knob member provided with a threaded axial interior bore 134. Threaded bore 134 engages a driving member 136 having an elongated threaded body portion 139. At its distal end, driving member 136 connects to driving rod member 137. Lateral longitudinal slots 138 in driving member 136 cooperate with through-pin 128 to permit axial translation of driving member 136 while prohibiting rotational movement.
Referring now to FIGS. 7 and 13, endoscopic section 140 includes a substantially cylindrical member 142 having slots 146 formed in a distal end thereof to accommodate the tissue spreading mechanism 150. Driving rod 137 coaxially traverses cylindrical member 142 to actuate the tissue spreading mechanism.
Vertebrae spreading mechanism 150 includes a pair of radially deployable serrated vertebrae spreading elements 152 linked together and biased to a non-deployed (closed) position through coil springs 160. Coil springs 160 are mounted by fasteners 162 within recesses 154 formed in the exterior of vertebrae spreading elements 152, best seen in FIGS. 10, 12, and 13.
As shown in FIG. 13, positioned at a distal end of driving rod 137 are a pair of camming elements 135 which deploy vertebrae spreading elements 152 through interaction with camming surfaces located on the inner surfaces 156 of the vertebrae spreading elements 152. Each camming element 135 includes a distal cylindrical portion 131 and a proximal frustoconical portion 133 tapering distally from the cylindrical portion.
When the vertebrae spreading elements 152 are in the retracted position, inner camming surfaces 156 create a stepped axial bore (see FIGS. 9, 11, and 13) defining a proximal frustoconical-shaped portion 157 adapted to engage proximal camming element 135 and tapering to a cylindrical bore 158 of diameter sufficient to accommodate driving rod 137. The diameter of cylindrical bore 158 stepwise increases (in distal direction) in region 159 to accommodate cylindrical portion 131 of distal camming element 135. From region 159, the bore tapers distally to define a frustoconical-shaped distal surface 155 which accommodates frustoconical portion 133 of distal camming element 135.
Atraumatic tip 144 is provided with a stepped axial bore 143 having a proximal frustoconical portion 147 and a cylindrical distal portion 148, best seen in FIG. 9. Stepped bore 143 provides a distal terminus for driving rod 137 and distal camming element 135 when vertebrae spreading elements 152 are in their deployed positions.
In use, rotation of actuating member 132 produces axial translation of driving member 136 and driving rod 137. Proximal camming element 135 moves distally through endoscopic member 142 as distal camming element 135 traverses cylindrical bore portion 159. During this initial motion, vertebrae spreading elements 152 remain stationary in their undeployed position as shown in FIG. 9. Vertebrae spreading elements 152 maintain the position shown in FIG. 9 until frustoconical portion 133 of proximal camming element 135 is positioned within proximal frustoconical bore portion 157 of vertebrae spreading elements 152 and frustoconical portion 133 of distal camming element 135 is positioned within distal frustoconical bore portion 155 of vertebrae spreading elements 152.
As frustoconical portion 133 of distal camming element 135 slides against distal frustoconical bore surface 155 and frustoconical portion 133 of proximal camming element 135 slides against proximal frustoconical bore surface 157, vertebrae spreading elements 152 are biased radially outwardly against the force of connector springs 160, as shown in FIGS. 11 and 12. The vertebrae spreading elements 152 continue moving radially outwardly until the are fully deployed. Full deployment corresponds to the position shown in FIG. 11 with the frustoconical portion 133 of distal camming element 135 fully engaged within frustoconical bore of elements 152. Thus, parallel movement, i.e. movement of vertebrae spreading elements in a direction transverse to the longitudinal axis of the instrument so the elements remain in planes substantially parallel to the longitudinal axis, is achieved. Rotation of actuating member 132 in the opposite direction retracts driving rod 137 and the vertebrae spreading elements 152 return to the original retracted position under the force of springs 160.
FIGS. 14-18 depict an alternative embodiment of a surgical instrument 200 useful as a tissue spreader and, more particularly, as a vertebrae spreader, according to the present invention. Vertebrae spreader 200 comprises a handle portion 220 housing an actuating member 232 and an elongated, substantially cylindrical endoscopic portion 240 extending from a distal end of the handle portion. A vertebrae spreading mechanism 250 is coupled to a distal end of the endoscopic portion. Vertebrae spreading mechanism 250 includes radially pivotal vertebrae spreading arms 252 mounted to endoscopic portion 240 through fasteners 245. Vertebrae spreading arms 252 extend through the distal end cap 247 of endoscopic portion 240. As best seen in FIG. 16, the vertebrae gripping surface 257 of each of vertebrae spreading arms 252 forms an acute angle of elevation, angle T, with the longitudinal axis towards the proximal end of instrument 200. This configuration aids in spreading vertebrae since the distalmost portion of the vertebrae spreading arms are narrower than the proximalmost portion, enabling insertion of the instrument within confined spaces.
As illustrated in FIGS. 15 and 16, handle portion 220 includes a chamber 222 for housing actuating member 232 and a through-bore 224 to engage portions of the driving mechanism. Actuating member 232 comprises a pair of rotatable toothed wheels 233 having central circular apertures 234 formed therein. Apertures 234 engage a drive sprocket 260 in an interference fit such that drive sprocket 260 rotates concurrently with wheels 233. Drive sprocket 260 traverses the width of handle portion 220, extending through handle bore 224 where it is fixed at each end by pivotal end caps 264.
Drive sprocket 260 engages a drive chain 270 through a circumferential array of hemispherical grooves 262 spaced to grip and drive adjacent spherical links 272 of drive chain 270. Drive chain 270 extends through endoscopic portion 240 of instrument 200 to a drive sprocket 280. Like drive sprocket 260, sprocket 280 includes a circumferential array of hemispherical grooves 282 which are engaged by spherical links 272 of drive chain 270.
Sprocket 280 circumscribes transverse threaded rod 290 for pivoting vertebrae spreading arms 252. Fasteners 245 are mounted through apertures 256 as pivot points, and vertebrae spreading arms 252 are spread radially outward by threaded rod 290 interengaging their threaded apertures 254. Threaded rod 290 is divided into right and left threaded half sections 292 and 294 respectively. As threaded rod 290 rotates, both arms 252 are pivoted radially outward through provision of rod half sections threaded in opposite directions.
In use, counterclockwise rotation of actuating member 232 produces a corresponding rotation of drive sprocket 260. Drive sprocket 260 drives chain 270 counterclockwise, resulting in counterclockwise rotation of sprocket 280 and threaded rod 290. Engagement of right and left threaded portions 292 and 294 of rod 290 with threaded apertures 254 of vertebrae spreading arms 252 pivots the arms 252 radially outward about pivot points 245, as shown in FIG. 17.
FIGS. 19-23 illustrate another alternative embodiment of a surgical instrument 400 useful as a tissue spreader, and, more particularly as a vertebrae spreader according to the present invention. Surgical instrument 400 comprises handle portion 420 having an actuating member 432 extending proximally therefrom. Elongated, substantially cylindrical endoscopic portion 440 extends distally from the handle portion 420. A vertebrae spreading mechanism 460 is coupled to a distal end of endoscopic portion 440. Vertebrae spreading mechanism 460 includes a housing 461 mounting a pair of vertebrae spreading arm members 462, shown in an open position in FIG. 19A.
As shown in FIG. 20, the handle portion 420 includes handle half-sections 422 and 424 having grip-enhancing knurled outer surfaces. Radially inwardly projecting pins 429 engage corresponding apertures 421 to ensure proper alignment of the half-sections 422, 424. When assembled, half sections 422 and 424 define an axial bore 426 which houses the actuation assembly 430.
Actuation assembly 430 includes a rotatable knob member 432 capped with an end cap 434 and having an externally threaded proximally-extending cylindrical portion 435 defining an interior bore 438. The cylindrical portion 435 is threadably engaged within internally threaded spool-shaped retainer 437 which interfits within the axial bore 426 of the handle portion 420 of the instrument. Retainer 437 maintains the axial alignment of rotatable knob member 432 and provides a distal end point for the knob member 432.
Received within interior bore 438 of knob member 432 is actuating link 439 having an internally threaded bore. Bolt 433 fixes actuating link 439 within bore 438. Longitudinally extending bolt 433 extends through a washer 436 into the cylindrical portion 435 of knob member 432 where it is threadably engaged within the actuating link 439. The relationship of bolt 433 within the knob 432 is such that the bolt does not rotate as the knob is turned, but translates distally along the longitudinal axis with the knob. Consequently, actuating link 439 is translated distally, without any rotational motion component.
Referring now to FIGS. 20, 22 and 23, actuating link 439 fixedly receives an actuating rod 442 within its distal bore. Actuating rod 442 coaxially extends through the endoscopic portion 440 of the instrument and terminates in a camming mechanism 450. Camming mechanism 450 includes a pair of wedge-shaped camming elements 452 for engaging camming surfaces 463 of vertebrae spreading arm members 462. Camming elements 452 include projections 453 to interfit with grooves 454 in the camming surfaces 463 of the vertebrae spreading arms 462. The system of grooves 454 and projections 453 ensure axial alignment of the vertebrae spreading arms 462 as they are deployed and serve as a return mechanism for the arms.
Vertebrae spreading arms 462 are connected to housing 461 and biased to a closed position by four tension coil springs 464. Each spring 464 is fastened at a first hook-shaped end to housing 461 and fastened at the opposite hook-shaped end to vertebrae spreading arm 462 through fasteners 465. To ensure axial alignment of the arms 462, groove and alignment pin system 469 is provided on the interior portion. When mounted to housing 461 in the closed position, FIGS. 19 and 22, knurled exterior portion 467 of arm 462 is flush with the edges of housing 462, while camming surfaces 463 are seated over camming elements 452 within the housing interior.
Distal wedge-shaped nose portions 466 of the vertebrae spreading arm 462 extend beyond the distal end of housing 461 to initially engage the tissue structure to be spread. This allows the instrument 400 to be placed within confined spaces, such as between vertebrae bodies, and gradually spread apart adjacent members.
When surgical instrument 400 is actuated through rotation of knob 432, the camming elements 452 of actuating rod 442 are driven distally, forcing the vertebrae spreading arms 462 radially outward against springs 464 as shown in FIG. 23. Rotation of knob 432 in the opposite direction pulls actuating rod 442 and its associated camming elements 452 in the opposite direction, allowing the vertebrae spreading arms 462 to return to their original retracted position under the force of coil springs 464.
In an alternate embodiment shown in FIG. 23A, which eliminates springs 464, camming elements 482 (only one is shown) of camming mechanism 450 includes a transverse guide pin 484 mounted via support 486 and extending into a elongated slot 488 formed in each of the vertebrae spreading arms. The slot 488 is dimensioned to loosely receive guide pin 486 so that during the movement of the arms to the open position, the guide pin 488 does not bear any load. However, during return of the arms to their closed position, the pin 488 rides in the bottom edge of slot 488 and partially bears the load.
FIGS. 28-32 illustrate a shielded endoscopic cutting implement 600 according to the present invention. Endoscopic cutting implement 600 is especially useful for cutting a herniated nucleus pulposus during an endoscopic discectomy procedure, although it can be used in other procedures. Endoscopic cutting implement 600 includes a handle portion 620, an elongated endoscopic portion 640, and a distal knife portion 660, shown in the deployed position in FIG. 28A.
As best seen in FIGS. 29-31, handle portion 620 comprises a stepped cylindrical actuation member 622 having an axial bore 623 with a longitudinally extending threaded fastener 632 received therein. Distal portion 621 of cylindrical actuation member 622 is received within a sleeve member 626 such that it is rotatable and axially translatable within the sleeve member. Sleeve member 626 includes a longitudinal slot 627 for engaging an actuation pin 625. The longitudinal slot 627 has transversely extending notch portions 628 and 629 respectively formed in its proximal and distal ends for engaging an actuation pin 625 in the closed and open positions of the instrument. Aperture 624, formed within narrowed distal portion 621 of actuation member 622, receives actuation pin 625.
Endoscopic section 640 includes an endoscopic tubular member 642 secured within the distal end of sleeve 626 and extending distally therefrom. The endoscopic section 640 further includes an actuation rod 630 having a threaded axial shaft at its proximal end. Actuation rod 630 coaxially extends through the endoscopic tubular member 642 and sleeve 626 to threadably engage threaded bore 632 of actuation member 622. Actuation rod 630 is provided with transverse bore 633 adjacent its proximal end for receiving actuation pin 625.
At its distal end, actuation rod 630 terminates in knife blade housing 650. As seen best seen in FIG. 32, blade housing 650 has a cylindrical proximal portion 652 having a bore 655 for receiving the distal end of actuation rod 630. Proximal portion 652 of housing 650 further includes a circumferential groove 657 to seat gaseous seal member 653. Although illustratively depicted as an O-ring, the gaseous seal may comprise silicone grease or other known gaseous seals.
At its distal end, blade housing 650 terminates in a narrow slit 654 which forms an oblique angle with respect to the longitudinal axis of the instrument. Housing slit 654 frictionally engages a knife blade 662. Knife blade 662 has cutting edge 663 and tapers distally to form pointed tip 664. It is understood by those skilled in the art that variously configured knife blades may be received within housing member 650 depending upon the type of surgical procedure to be performed.
In use, surgical instrument 600 is provided with the knife blade 662 retracted within endoscopic tubular member 642. This position corresponds to actuation pin 625 located within proximal notch 628 of longitudinal slot 627 of sleeve member 626. To extend knife blade 660, cylindrical actuation member 622 of handle portion 620 is rotated clockwise (as viewed from the proximal to distal end) to move actuation pin 625 into the longitudinal portion of slot 627. Actuation member 622 is then advanced distally within sleeve 626 and actuation pin 625 travels distally within slot 627. As actuation member 622 moves distally, actuation rod 630 extends housing 650 and knife blade 662 beyond the endoscopic tubular member 642. When actuation pin 625 reaches the distal end of longitudinal slot 627, the knife blade 662 is fully extended. To lock the knife blade 660 in its extended position, the handle portion cylindrical member 622 is first rotated clockwise to move actuation pin 625 into distal notch 629. To retract knife blade 660, actuation member 622 is rotated in the opposite direction so that actuation pin 625 is moved into the longitudinal portion of slot 627 and then pulled proximally. Rotation of pin 625 into proximal notch 628 will lock the knife blade 660 in the retracted position.
B. Surgical Method
Use of the surgical instruments of FIGS. 1-32 will be described in conjunction with an anterior endoscopic lumbar discectomy according to the present invention. While they have particular application in this procedure, it is recognized that the instruments of the present invention may be used to perform surgical spreading and cutting procedures anywhere in the body. In describing the procedure, the term "anterior" is broadly used to describe the ventral surface of a body opposite the back. This term includes, but is not limited to, the abdominal region of the body.
For performing an anterior endoscopic lumbar discectomy, the patient is placed in the supine position and entry is made through the abdomen, which is insufflated according to known procedures. Specific points of entry are determined by the particular intervertebral disc to be removed. For removal of intervertebral discs of the lumbar vertebrae, ports are established in the lower abdomen using standard trocars. One port is dedicated to viewing via an endoscope, while remaining ports are used for surgical instrument insertion and manipulation.
To access the intervertebral disc, soft tissue is dissected, providing a pathway through the abdominal region. Fascia and other soft tissue may be spread using the tissue spreader of FIG. 1 or FIG. 24. Organs such as the colon are retracted away from the operating site to increase exposure and facilitate observation of the spinal column.
Upon reaching the spinal column, blunt dissection is performed to expose the intervertebral disc. Fascia is removed from the disc area and spread using the tissue spreader of FIG. 24 to create an access opening or by placing a tissue spreading element in the fascia using the instrument of FIG. 1.
To further facilitate access to the intervertebral disc, the adjacent vertebrae are spread using any of the vertebrae spreaders of the present invention. The distal end of the selected instrument is placed between the vertebral bodies. Deployment of the vertebrae spreader causes the arms to expand against each adjacent vertebral body, relieving pressure on the disc to ease disc removal.
The herniated disc nucleus is accessed through the disc annulus. The disc annulus may be incised using the endoscopic cutting instrument of FIG. 28. A portion of the disc annulus may be removed to form an access channel or an incision may be created and the incision edges spread open through the tissue spreading element deployed by the instrument of FIG. 1. Alternatively, the disc annulus may be incised using a laser or an access port created using a trephine.
The endoscopic cutting instrument of FIG. 28 is inserted into the disc nucleus. Following insertion into the disc nucleus and extension of the knife blade, the cutting instrument slices away portions of the disc nucleus which may be removed using forceps, rongeurs, or suction instruments. Other instruments may be selected for disc removal including lasers, rongeurs, shavers, and the like. Using the anterior approach, as much or as little of the herniated nucleus may be removed as needed to alleviate compression of adjacent muscles and nerves. This surgical procedure permits the surgeon to directly monitor the disc removal process by means of an endoscope.
The instruments described above are preferably composed of relatively inexpensive materials so that they are single-use disposable instruments which can be discarded after use. However, it is also contemplated that they can be re-usable or semi-reusable in that a portion of the instrument is re-sterilized, e.g. the hand, and the remaining portion is disposable, e.g. the jaw structure.
Although the instrumentation of the present invention has been described for use in endoscopic discectomy procedures, the instruments can be used for facilitating other endoscopic (minimally invasive) surgical procedures. These include, for example, spreading the vertebrae to aid spinal fusion. Spinal fusion is used to stabilize spinal segments and is currently performed using fusion baskets, bone plugs or other internal fixation devices.
While the invention has been particularly shown and described with reference to the preferred embodiments, it will be understood by those skilled in the art that various modifications and changes in form and detail may be made without departing from the scope and spirit of the invention. Accordingly, modifications such as those suggested above, but not limited thereto, are to be considered within the scope of the invention. | The present invention provides endoscopic instrumentation and surgical techniques especially useful for accessing and removing at least a portion of an intervertebral disc. Instrumentation includes tissue spreaders and cutting instruments. In particular, the tissue spreading instruments include instruments for spreading pre-sacral tissue such as fascia and for spreading adjacent vertebrae to facilitate access to the intervertebral disc. Endoscopic cutting instruments deliver a cutting blade in a sheathed position to the site of the disc nucleus followed by deployment to remove portions of the disc nucleus. | 0 |
ORIGIN OF THE INVENTION
The invention described herein was jointly made by employees of the U.S. Government and an employee of BASF A.G., and may be manufactured and used by or for the Government for governmental purposes without the payment of any royalties thereon or therefor.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to the field of poly(1,3,4-oxadiazoles) and more particularly to poly(1,3,4-oxadiazoles) created via aromatic nucleophilic displacement reaction of di(hydroxyphenyl)-1,3,4-oxadiazoles with activated aromatic dihalides and activated aromatic dinitro compounds.
2. Description of the Prior Art
Poly(1,3,4-oxadiazoles) (POX) are heterocyclic polymers which were first synthesized by the reaction of bistetrazoles and diacid chlorides. [C. J. Abshire and C. S. Marvel, Makromolecular Chemistry, 44/46, 388 (1961)]. Since then several different reaction pathways have been developed to prepare these polymers. The most popular synthesis involves the preparation of a precursor polyhydrazide by the reaction of a diacid chloride or derivative with hydrazine or a dihydrazine compound. This precursor polyhydrazide is cyclized to the POX by heating to 200°-300° C. under vacuum or heating in a high boiling dehydrating solvent such as sulfuric or polyphosphoric acid. [A. H. Frazer and F. T. Wallenberger, Journal of Polymer Science, A-2, 1137, 1147, 1157 (1964)]. A different synthetic procedure produces POX in one step by the solution polymerization of a dicarboxylic acid or the corresponding nitrile, amide, or ester with hydrazine or its salt in polyphosphoric or sulfuric acid. [Y. Iwakura, K. Uno and S. Hara, A3, 45 Journal of Polymer Science (1965)]. Another method involves the self-polymerizing reaction of a dihydrazide in polyphosphoric or sulfuric acid. [Y. Iwakura, K. Uno and S. Hara, Makromol. Chem., 94, 103 (1966)]. The final preparation of POX is accomplished through the cyclodeammonation reaction of poly(N-acylhydrazidines), also referred to as poly(N-acylamidrazones), by heating in strong acids such as refluxing trifluoroacetic acid or polyphosphoric acid at 200° C. [P. M. Hergenrother, Macromolecules, 3(1), 10 (1970); see also M. Saga and T. Shono, Journal of Polymer Science, B-4, 869 ( 1966)]. For a general review of poly(1,3,4-oxadiazoles) see "Thermally Stable Polymers" by P. E. Cassidy, Marcel Dekker, Inc. New York, p. 179; see also P. E. Cassidy and N. C. Fawcett, Journal of Macromolecular Science Reviews, C17(2), 209 (1979).
SUMMARY OF THE INVENTION
The primary object of this invention constitutes new compositions of matter and a new process to prepare poly(1,3,4-oxadiazoles). It concerns new POX, novel monomers, and the process for preparing the same.
Another object of the present invention is to provide new POX that are useful as adhesives, coatings, films, membranes, moldings, and composite matrices.
Another object of the present invention is the composition of several new di(hydroxyphenyl)-1,3,4-oxadiazole monomers.
According to the present invention, the foregoing and additional objects were obtained by synthesizing POX by the nucleophilic displacement reaction of di(hydroxyphenyl)-1,3,4-oxadiazole monomers with activated aromatic dihalides. The inherent viscosities (η inh ) of the POX ranged from 1.02 to 1.71 dL/g and the glass transition temperatures (T g ) ranged from 182° to 242° C. Several of the polymers exhibited crystalline melting temperatures (T m ) by differential scanning calorimity (DSC) and wide angle X-ray diffraction. The T m s ranged from 265° to 390° C. Thermogravimetric analysis showed no weight loss occurring below 300° C. in air or nitrogen with a 5% weight loss occurring at approximately 500° C. in air and nitrogen.
The synthesis of the POX involved the use of di(hydroxyphenyl)-1,3,4-oxadiazoles of two different types. The first type was prepared from 4-hydroxybenzoic hydrazide and phenyl-4-hydroxybenzoate (see equation 1). The second type of di(hydroxyphenyl)-1,3,4-oxadiazole was prepared by reacting two moles of 4-hydroxybenzoic hydrazide with an aromatic diacid chloride (see equation 2). The substitution of the hydroxy groups in either type of monomer may be meta-meta, para-para, or para-meta. The general reaction sequence for the synthesis of POX is represented in equations (3) and (4). ##STR1##
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention comprehends synthesizing POX via aromatic nucleophilic displacement reaction of novel di(hydroxyphenyl)-1,3,4-oxadiazoles of two types with activated aromatic dihalides or activated aromatic dinitro compounds. The general reaction sequence is represented in equation (5). ##STR2## Y is a chloro, fluoro, or nitro group. X is a radical selected from the group consisting of: ##STR3## wherein Ar is selected from the group consisting of: ##STR4## where Ar' is selected from the group consisting of: ##STR5## and where n is an integer between 4 and 100. Substitution of the hydroxy radicals may be meta-meta, para-para, or para-meta. The reaction is carried out in a polar aprotic solvent selected from the group consisting of N,N-dimethylacetamide, N-methylpyrrolidone, sulfolane, diphenylsulfone, N-cyclohexylpyrrolidone, and dimethylsulfoxide, using an alkali metal base such as K 2 CO 3 , Na 2 CO 3 , KOH, and NaOH. The reaction is then carried out with the application of heat under nitrogen.
The first type of novel di(hydroxyphenyl)-1,3,4-oxadiazole monomer was prepared by reacting 4-hydroxybenzoic hydrazide and phenyl-4-hydroxy benzoate. The reaction is given by equation (1) above. The reaction is carried out with the application of heat under nitrogen.
The second type of novel di(hydroxyphenyl)-1,3,4-oxadiazole monomer was prepared by reacting two moles of 4-hydroxybenzoic hydrazide with an aromatic diacid chloride. The general reaction mechanism is given by equation (2). This reaction is carried out at approximately 0° C. The resulting product from the reaction is an intermediate dihydrazide which is collected and then placed in a vacuum oven and heated to a high temperature to achieve cyclodehydration to the oxadiazole.
Having generally described the invention, a more complete understanding thereof may be obtained by reference to the following examples which are provided herein for purposes of illustration only and do not limit the invention.
EXAMPLES
Example I
The following example illustrates the reaction sequence shown in equation 1 above for the preparation of the monomer and the reaction sequence shown in equation 3 above for the preparation of the polymer, where X is equal to a sulfone group and Y is Cl.
Monomer Synthesis
2,5-Bis(4-hydroxyphenyl)-1,3,4-Oxadiazole
Into a 250 ml three neck round bottem flask equipped with a magnetic stirbar, nitrogen inlet, glass stopper and distillation head is placed 4-hydroxybenzoic hydrazide (60.9 g, 0.4 mol) and phenyl-4-hydroxybenzoate (85.7 g, 0.4 mol). The mixture is heated to approximately 210° C. by use of a Wood's metal bath. The solids melt and phenol begins to evolve and is removed via the distillation head. The melt begins to solidify after about 15-20 minutes. The temperature is then increased to 300° C. and held for approximately one hour while under nitrogen. After cooling, the tan solid is pulverized and stirred with methanol (150-200 ml). The undissolved solid is collected and dried at 150° C. in a forced air oven. The white solid (approximately 56 g) is recrystallized from N,N-dimethylacetamide (DMAc, 225 ml) and water (105 ml) and after drying at 200° C. under vacuum (45.7 g, 45% yield), it exhibited a melting point of 347° C. by differential thermal analysis (DTA). [Y. Iwakura, U. Keikichi, Y. Imai, and Y. Takase, Die Makromoleculare Chemie, 95, 261 (1966) melting point 338° C.]. Elemental analysis for C 14 H 10 O 3 N 2 . Calculated: C, 66.13%; H, 3.96%; O, 18.88%; N, 11.02%. Found C, 66.17%; H, 4.05%; N, 11.12%.
Poly(1,3,4-oxadiazole) Synthesis
Into a 100 ml three neck round bottom flask equipped with a mechanical stirbar, thermometer, N 2 inlet an reflux condenser is placed 2,5-bis(4-hydroxyphenyl)-1,3,4-oxadiazole (2.5424 g, 0.01 mol), diphenylsulfone (20 g, 19% solids) and pulverized anhydrous potassium carbonate (3.2 g, 0.023 mol, 15% excess). The mixture is heated to approximately 180° C. under nitrogen. After about 20 minutes at this temperature 4,4'-dichlorodiphenylsulfone (2.8716 g, 0.01 mol) is added. The temperature is increased to about 210° C. for 16 hours under nitrogen. The viscous reaction mixture is diluted with N-methylpyrrolidone (NMP, 20 ml) at 200° C. and precipitated into methanol/acetic acid mixture in a high speed blender. The polymer is collected, washed successively with hot methanol, hot water and hot methanol and dried at 120° C. for 16 hours in a forced air oven. The polymer[yield 4.5 g (96%)] exhibited a glass transition temperature of 226° C. and an inherent viscosity (0.5% solution in m-cresol solution at 25° C.) of 1.02 dL/g. Thin films cast from m-cresol solution gave tensile strength, tensile modulus and elongation at 25° C. of 11.6 Ksi, 304.2 Ksi and 7.5% and at 150° C. of 7.7 Ksi, 274.0 Ksi and 4.3% respectively.
Example II
The following example illustrates the reaction sequence for the preparation of the POX as shown in equation 3 above where X equals an isophthaloyl group and Y equals F.
Into a 100 ml three neck round bottom flask equipped with a mechanical stirrer, thermometer, N 2 inlet, and reflux condenser is placed 2,5-bis(4-hydroxyphenyl)-1,3,4-oxadiazole (2.5424 g, 0.01 mol), diphenylsulfone (23 g, 19% solids), and pulverized anhydrous potassium carbonate (3.2 g, 0.023 mol, 15% excess). The mixture is heated to approximately 180° C. under nitrogen. After about 20 minutes at this temperature 1,3-bis(4-fluorobenzoyl)benzene (3.2230 g, 0.01 mol) is added. The temperature is increased to approximately 210° C. for 16 hours under nitrogen. The viscous reaction mixture is diluted with NMP (20 ml) at 200° C. and precipitated into methanol/acetic acid mixture in a high speed blender. The polymer is washed successively with hot methanol, hot water, and hot methanol and dried at 120° C. for 16 hours in a forced air oven. The polymer [yield 5.25 g (98%)] exhibited a glass transition temperature of 182° C. and a melting transition temperature of 265°. The inherent viscosity (0.5% solution in m-cresol at 25° C.) was 1.53 dL/g. Thin films cast from m-cresol solution gave tensile strength, tensile modulus and elongation at 25° C. of 15.0 Ksi, 414.3 Ksi, and 4.3% and at 150° C. of 7.4 Ksi and 10.7% respectively.
Example III
The following example illustrates the reaction sequence for the preparation of the monomer (1,3-isomer) as shown in equation 2 and for the preparation of the POX as shown in equation 4 above where X is an isophthaloyl group and y equals F.
Monomer Sythesis
2,2'-(1,3-Phenylene)bis[5-(4-hydroxyphenyl)-1,3,4-oxadiazole]
Into a 250 ml three neck round bottom flask equipped with a magnetic stirbar, thermometer, addition funnel, and glass stopper is placed 4-hydroxybenzoic hydrazide (6.0 g, 0.039 mol) and dry DMAc (90 ml). After the solid dissolves the solution is cooled to approximately 0° C. via an ice water bath. A solution of isophthaloyl chloride (4.0 g, 0.0195 mol) in dry DMAc (30 ml) is placed in the addition funnel. The isophthaloyl chloride solution is added dropwise over approximately one hour while maintaining the reaction temperature between 0° and 5° C. After the entire solution has been added, the ice bath is removed and the solution is allowed to warm to room temperature, stirring is continued for 16 hours. The DMAc solution is poured into ice/water to give a white precipitate which is collected by filtration and subsequently dried at 70° C. under vacuum. Yield 7.1 g (76%) of the intermediate dihydrazide, m.p. 298° C. (DTA). The intermediate dihydrazide (6.0 g) is placed in a vacuum oven and heated to 280° C. for approximately 4 hours to achieve cyclodehydration to the oxadiazole. The solid is pulverized and washed in hot ethanol to yield a yellow solid (4.3 g, 85%) m.p. greater than 400° C. The solid is used without further purification.
Polymer Synthesis
Into a 100 ml three neck round bottom flask equipped with a mechanical stirbar, thermometer, N 2 inlet, and reflux condenser is placed 2,2'-(1,3-phenylene)bis[5-(4-hydroxyphenyl)-1,3,4-oxadiazole] (3.9836 g, 0.01 mol), diphenylsulfone (28 g, 19% solids) and pulverized anhydrous potassium carbonate (3.2 g, 0.023 mol, 15% excess). The mixture is heated to approximately 180° C. under nitrogen. After about 20 minutes at this temperature, 1,3-bis(4-flourobenzoyl)benzene (3.2231 g, 0.01 mol) is added. The temperature is increased to 210°-220° C. and the mixture is stirred for 16 hours under nitrogen. The viscous reaction mixture is diluted with NMP (30 ml) at 200° C. and precipitated into methanol/acetic acid mixture in a high speed blender. The polymer is washed successively with hot methanol, hot water, and hot methanol and dried at about 120° C. for 16 hours in a forced air oven. The polymer [ yield 6.7 g (98%)] exhibited a glass transition temperature of 200° C. The inherent viscosity (0.5% solution in concentrated sulfuric acid at 25° C.) was 0.36 dL/g.
Polymer characterization data and thin film properties of particular polymers are set forth in the following Tables 1 and 2.
TABLE 1__________________________________________________________________________POLYMER CHARACTERIZATION ##STR6##POLYMER X η.sub.inh, dL/g T.sub.g, °C. T.sub.m, °C.__________________________________________________________________________P1 ##STR7## 1.38 242 --P2 SO.sub.2 1.02 226 --P3 ##STR8## 1.57 205 325P4 ##STR9## 1.71 201 390P5 ##STR10## 1.53 182 265__________________________________________________________________________
TABLE 2__________________________________________________________________________THIN FILM PROPERTIES TEST TENSILE TENSILEPOLYMER TEMP., °C. STRENGTH, KSI MODULUS, KSI ELONG., %__________________________________________________________________________P1 23 11.1 334.2 7.1 150 7.9 301.9 3.6P2 23 11.6 304.2 7.5 150 7.7 274.0 4.3P5 23 15.0 414.3 4.3 150 7.4 365.2 10.7__________________________________________________________________________ | Poly(1,3,4-oxadiazoles) (POX) are prepared by the aromatic nucleophilic displacement reaction of di(hydroxyphenyl)-1,3,4-oxadiazole monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The polymerizations are carried out in polar aprotic solvents such as sulfolane or diphenylsulfone using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. The di(hydroxyphenyl)-1,3,4-oxadiazole monomers are synthesized by reacting 4-hydroxybenzoic hydrazide with phenyl-4-hydrobenzoate in the melt and also by reacting aromatic dihydrazides with two moles of phenyl-4-hydroxybenzoate in the melt. This synthetic route has provided high molecular weight POX of new chemical structure, is economically and synthetically more favorable than other routes, and allows for facile chemical structure variation due to the large variety of activated aromatic dihalides which are available. | 2 |
BACKGROUND
Unlike the ethyl and higher trialkylaluminum compounds which can be made economically by reactions of aluminum, hydrogen, and an olefin, trimethylaluminum has been produced only by processes which begin with a methyl halide. These include the direct reaction of a methyl halide with aluminum metal to form the methylaluminum sesquihalide, followed by a reduction step generally utilizing sodium as the reducing agent. Thus, starting with methyl chloride as a source of the methyl group:
3CH.sub.3 Cl+2Al→(CH.sub.3).sub.3 Al.sub.2 Cl.sub.3
(CH.sub.3).sub.3 Al.sub.2 Cl.sub.3 +3Na→(CH.sub.3).sub.3 Al+3NaCl+Al
This process has been used on a commercial scale to produce trimethylaluminum. Processes of this type are described in an article by A. V. Grosse and J. M. Mavity, Journal of Organic Chemistry, 5, 106 (1940), and in U.S. Pat. Nos. 2,863,894 and 2,954,389.
U.S. Pat. No. 2,744,127 describes a related method involving the direct reaction of a 40Al/60Mg alloy with a methyl halide, according to the equation:
CH.sub.3 Cl+Al.sub.2 Mg.sub.3 →2(CH.sub.3).sub.3 Al+3MgCl.sub.2
A method described in U.S. Pat. No. 2,839,556 does not use a reducing metal but is based on formation of cryolite as a means of removing halogen from a methylaluminum halide. For example,
(CH.sub.3).sub.2 AlCl+NaF→(CH.sub.3).sub.2 AlF+NaCl
3(CH.sub.3).sub.2 AlF+3NaF→2(CH.sub.3).sub.3 Al+Na.sub.3 Al.sub.2 F.sub.6
All of the above-described methods have the disadvantage of forming very large amounts of inorganic metal halide by-products. These materials not only have very low value, but are also generally produced in forms which makes their recovery uneconomical. Hence they must be disposed of in a safe and ecologically acceptable manner, which adds further economic penalty to the trimethylaluminum synthesis.
Reviews of organoaluminum compound synthesis, e.g., in "Organoaluminum Compounds" by T. Mole and E. A. Jeffery (Elsevier, N.Y., 1972) describe other methods of trimethylaluminum synthesis generally not useful for economic commercial production. These include the initial preparation of a Grignard reagent, CH 3 MgX, and its reaction with an aluminum halide in an ether solvent,
3CH.sub.3 MgX+AlX.sub.3 →(CH.sub.3).sub.3 Al+3MgX.sub.2
which cannot be removed readily from the trimethylaluminum product. Another route, which has been of academic interest only, is initial synthesis of very toxic dimethylmercury (from a CH 3 MgX reagent), from which the mercury can be displaced by aluminum in a solvent-free reaction.
3(CH.sub.3).sub.2 Hg+2Al→2(CH.sub.3).sub.3 Al+3Hg
A recent patent, U.S. Pat No. 4,118,409, provides for jointly making trimethylaluminum and alkylaluminum bromides and iodides in an alkyl exchange process by mixing an aluminum trialkyl, such as triethylaluminum, and a methylaluminum bromide or iodide and then distilling from the mixture trimethylaluminum as a first fraction and then alkylaluminum bromides or iodides as a subsequent fraction.
Still more recently S. P. Diefenbach has described several methods for making trimethylaluminum from triethylaluminum. In U.S. Pat No. 4,364,872, triethylaluminum is reacted with a methyl halide in the presence of a catalyst formed from a bismuth compound, e.g. BiCl 3 . The reaction is conducted in an autoclave.
Diefenbach U.S. Pat No. 4,364,873 describes a similar process using a catalyst formed from a vanadium compound (e.g. VOCl 3 ), a trialkylaluminum (e.g. triethylaluminum) and an alkyl iodide.
Diefenbach U.S. Pat. No. 4,364,474 describes a trimethylaluminum process using a non-catalyzed alkyl exchange between a higher trialkylaluminum such as triethylaluminum and methyl iodide.
Of the foregoing alkyl exchange systems, the most cost-effective process appears to be that shown in U.S. Pat. No. 4,364,872. Although the process of U.S. Pat. No. '872 is very effective on a laboratory scale, certain problems are encountered in conducting the process on a commercial scale. In U.S. Pat. No. '872, all of the tri-C 2+ alkylaluminum and methyl halide is present together with the bismuth catalyst at the start of the reaction in a sealed autoclave. As the reaction proceeds, methyl halide is consumed and C 2+ alkyl halide forms so the ratio of alkyl halide to trialkylaluminum is always high during the process. Alkyl halide can react with trialkylaluminum to form various alkylaluminum halides which consumes either trimethylaluminum product or the higher trialkylaluminum used as a reactant forming alkylaluminum halide.
Of greater concern in reaction mixtures containing high ratios of alkyl halide to alkylaluminum compound, is the possibility of a thermal excursion in a large scale reactor which can lead to an explosive reaction between the alkylaluminum compounds and the alkyl halides.
SUMMARY
According to the present invention, an improvement is provided in the process of U.S. Pat No. 4,364,872 whereby methyl halide is fed to the reaction zone at a controlled rate while concurrently distilling C 2+ alkyl halide from the reaction zone thereby avoiding the presence of large amounts of both aluminum trialkyls and alkyl halides in the reaction zone at the same time.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
A preferred embodiment of the process resides in an improvement in a process for making trimethylaluminum by reacting a methyl halide with a trialkylaluminum which has at least two carbon atoms in its alkyl groups in the presence of a catalyst formed from a bismuth compound and recovering trimethylaluminum from the resultant reaction mixture. According to the improvement, methyl halide is added to a reaction mixture containing a tri-C 2+ aluminum alkyl and said catalyst formed from said bismuth compound at a controlled rate such that said methyl halide reacts as it is added to form trimethylaluminum and C 2+ alkyl halide while continuously distilling said C 2+ alkyl halide and any unreacted methyl halide from the reaction zone thereby avoiding accumulation of either methyl halide or C 2+ alkyl halide in the reaction mixture.
The basic process is described in detail in Diefenbach U.S. Pat. No. 4,364,872 which is incorporated herein in its entirety as if fully set forth.
Trialkylaluminum compounds in which the alkyl groups contain at least two carbon atoms include triethylaluminum, tri-n-propylaluminum, tri-n-butylaluminum, tri-isobutylaluminum, tri-n-pentylaluminum, trihexylaluminum, trioctylaluminum. By far the most preferred tri-C 2+ alkyl aluminum compound is triethylaluminum because it is readily available at reasonable cost.
Useful methyl halides include methyl chloride, methyl bromide and methyl iodide.
Any bismuth compound can be used to prepare the catalyst. It is believed that the bismuth compound reacts with the trialkylaluminum to form a compound which contains bismuth, aluminum and alkyl groups and possibly other groups. It is not necessary to know the structure of the active catalyst specie in order to obtain the benefits of the reaction.
Preferred bismuth compounds are bismuth halides and organobismuth compounds. Examples are bismuth trichloride, bismuth triiodide, bismuth tribromide, bismuth trifluoride, triphenylbismuth, pentaphenylbismuth, trimethylbismuth, diphenylbismuth chloride, triethylbismuth, triphenylbismuth dichloride, bismuth triethoxide, bismuth triacetate, diethylbismuth bromide and the like.
Any trialkylaluminum can be used to form the catalyst including trimethylaluminum. In a most preferred embodiment bismuth trichloride is reacted with triethylaluminum to form the catalyst.
The amount of bismuth compound used in the process can vary over a wide range. A useful range is about 1-25 mole percent based on the total amount of tri-C 2+ alkyl aluminum used in the reaction. A preferred range is about 2-10 mole percent and most preferably about 3-7 mole percent.
The process can be conducted in a solvent although this is not essential. Useful solvents include the inert liquid aliphatic hydrocarbons such as hexane, octane, decane, cyclohexane, cyclooctane. Aromatics such as benzene, toluene, xylene and the like can be used although this may lead to some nuclear alkylation.
Useful reaction temperatures are those that cause the exchange reaction to proceed at a reasonable rate but not so high as to cause the reactants or products to undergo undesired decomposition. A useful temperature range is about 50°-75° C. A more preferred temperature range is about 90°-125° C. Temperatures above 127° C. will require some pressure in the reactor so the trimethylaluminum does not vaporize.
In one mode of operation, the process can be carried out by placing all of the tri-C 2+ alkyl aluminum reactant and the bismuth compound in a reaction vessel under an inert atmosphere such as nitrogen which is stirred and heated to reaction temperature. Then the methyl halide is introduced into the liquid phase at a controlled rate such that an excessive amount of methyl halide does not collect in the reactor. Most of the methyl halide will react with the tri-C 2+ alkyl aluminum under these conditions to form C 2+ alkyl halide. The reaction temperature must be high enough such that this C 2+ alkyl halide will vaporize from the reaction mixture. For example ethyl chloride has a normal boiling point of 12.3° C., ethyl bromide 38.4° C. and n-butyl chloride 78.5° C.
The reaction is conducted at atmospheric pressure or close to atmospheric pressure so the lower C 2+ alkyl halide will readily vaporize. Part of the methyl halide will also escape the liquid reaction phase and be conducted from the reaction vessel together with the C 2+ alkyl halide. In practice about 4-5 moles of methyl halide will be injected into the liquid reaction phase per mole of tri-C 2+ alkyl aluminum to be converted to trimethylaluminum. The vented methyl halide and C 2+ alkyl halide can be condensed and separated by conventional means.
Progress of the reaction can be monitored by periodically withdrawing small samples and analyzing them. When the reaction is complete, trimethylaluminum can be recovered from the reaction mixture by fractionation. Trimethylaluminum has a normal boiling point of 127° C. so the distillation can be conducted at atmospheric pressure. If desired, the fractionation can be conducted at reduced pressure if the system is leak-proof.
Another mode of operation comprises:
(A) forming a catalyst mixture in a reaction zone by reacting a trialkylaluminum with a bismuth compound,
(B) continuously feeding to said reaction zone (i) trialkylaluminum wherein the alkyl groups contain at least two carbon atoms and (ii) at least a stoichiometric amount, based on the formation of trimethylaluminum, of a methyl halide whereby said trialkylaluminum feed and said methyl halide react to form trimethylaluminum and a C 2+ alkyl halide,
(C) continuously distilling said C 2+ alkyl halide and any unreacted methyl halide from said reaction zone and
(D) recovering trimethylaluminum from said reaction zone.
In this embodiment the reactants and catalysts are the same as in the previous embodiment. It differs in that both the methyl halide and tri-C 2+ alkyl aluminum are continuously fed to the reaction zone which contains the catalyst. The catalyst is preferably formed in the reaction zone by combining a trialkylaluminum and a bismuth compound in an aliphatic hydrocarbon solvent having at boiling point above the reaction temperature. Normal decane (b.p. 174° C.) is a preferred solvent. The mixture is stirred and heated to reaction temperature and then both tri-C 2+ alkyl aluminum, e.g. triethylaluminum, and methyl halide are concurrently fed to the reaction zone at a controlled rate. The methyl halide is preferably injected into the liquid phase. A preferred mole ratio of methyl halide to tri-C 2+ alkyl aluminum is about 3-6:1 and more preferably about 4-5:1.
The methyl halide will enter into an alkyl exchange reaction with the tri-C 2+ alkyl aluminum forming trimethylaluminum and C 2+ alkyl halide. The C 2+ alkyl halide will vaporize at the reaction temperature and be conducted out of the reaction zone. As before, a portion of the methyl halide will escape the liquid phase and pass out of the reactor together with the C 2+ alkyl halide. This is why a stoichiometric excess of methyl halide is used.
After the addition of the tri-C 2+ alkyl aluminum and methyl halide is complete, the mixture is stirred at reaction temperature and then analyzed to be sure most of the tri-C 2+ alkyl aluminum has been converted to trimethylaluminum. Trimethylaluminum can then be recovered from the reaction mixture by fractionation.
The process can also be conducted in a continuous manner comprising:
(A) forming a catalyst mixture in a reaction zone by reacting a trialkylaluminum with a bismuth compound,
(B) continuously feeding to said reaction zone (i) trialkylaluminum wherein the alkyl groups contain at least two carbon atoms and (ii) at least a stoichiometric amount, based on the formation of trimethylaluminum, of a methyl halide whereby said trialkylaluminum feed and said methyl halide react to form trimethylaluminum and a C 2+ alkyl halide,
(C) continuously distilling said trimethylaluminum, said C 2+ alkyl halide and any unreacted methyl halide from said reaction zone and,
(D) recovering trimethylaluminum from the distillate.
This embodiment of the process uses the same reactants and catalyst as the previous embodiment. It also uses the same concurrent addition of both methyl halide and tri-C 2+ alkyl aluminum to the reaction zone using a stoichiometric excess of methyl halide. It differs in that the reaction temperature and pressure are such that the trimethylaluminum formed in the reaction distills out together with the C 2+ alkyl halide and any unreacted methyl halide. Since trimethylaluminum has a normal boiling point of about 127° C. it is preferred to conduct this embodiment above 127° C., for example 130°-175° C., more preferably 135°-150° C. Optionally the process can be conducted at reduced pressure to lower the boiling point of trimethylaluminum. Reduced pressure operation is not preferred because of the hazards of any air leak into the reaction system which could lead to a violent reaction.
The continuous process can also be conducted with an inert solvent in the reaction zone which boils higher than trimethylaluminum. Aliphatic hydrocarbons such as n-decane are preferred.
The vapor removed is preferably condensed in two stages. The first condenser is operated at a temperature such that the trimethylaluminum condenses but not the alkyl halides. The alkyl halides are then condensed downstream in a second condenser operated at a lower temperature.
The following examples serve to show how the process is carried out.
EXAMPLE 1
A 250-ml three-necked round bottomed reaction flask which was equipped with a one-inch Teflon coated magnetic stirring bar, a quarter-inch Teflon dip tube, and a thermometer was fitted to an eight-inch Vigreax distillation column which in turn was fitted to a condenser and receiving flask. Under an atmosphere of dry nitrogen, the reaction flask was charged with BiCl 3 (1.6 g, 5.1 mmol) and n-decane (26 g) after which triethylaluminum (12.4 g, 109 mmol) was added dropwise while stirring. The temperature rose to 40° C. and a black precipitate formed. While stirring continuously, the mixture was heated to 120° C. and then gaseous methyl bromide (41.6 g, 438 mmol) was bubbled into the liquid phase through the dip tube over three hours. The black precipitate disappeared a few minutes after methyl bromide was first introduced. The reaction flask was cooled after all of the methyl bromide had been added. Distillate of 34 g, which collected in the receiving flask, was analyzed and found to contain 26 g ethylbromide and 8 g methyl bromide. The liquid in the reaction flask separated into two phases. The lower phase (2.2 g) was the catalyst. The upper phase was analyzed and contained 6.4 g trimethylaluminum and 0.90 g dimethylaluminum bromide; 83% of the upper phase was fractionally distilled to isolate 4.8 g trimethylaluminum (isolated yield=74%).
EXAMPLE 2
A reactor and distillation apparatus identical to that described in Example 1 was assembled. Under an atmosphere of dry nitrogen, the reaction flask was charged with BiCl 3 (1.6 g, 5.1 mmol) and n-decane (27 g) after which triethylaluminum (12.5 g, 109 mmol) was added over two minutes while stirring, whereupon a black precipitate formed. While stirring continuously, the mixture was heated to 120° C. and then, over the course of one hour, gaseous methyl bromide (42.1 g, 443 mmol) was bubbled into the liquid phase through the dip tube. The black precipitate disappeared a few minutes after methyl bromide was first introduced. The reaction flask was cooled after all of the methyl bromide had been added. The liquid in the reaction flask separated into two phases. The lower phase (3.0 g) was the catalyst. The upper phase was analyzed and contained triethylaluminum (2.8 g, 25 mmol), trimethylaluminum (4.5 g, 62 mmol) and dimethylaluminum bromide (0.63 g, 4.6 mmol).
EXAMPLE 3
A reactor and distillation apparatus identical to that described in Example 1 was assembled. Under an atmosphere of dry nitrogen, the reaction flask was charged with BiCl 3 (1.6 g, 5.1 mmol) and then triethylaluminum (12.3 g, 108 mmol) was added dropwise while stirring, whereupon a black precipitate formed. While stirring continuously, the mixture was heated to 120° C. and then, over the course of one hour, gaseous methyl bromide (40.7 g, 429 mmol) was bubbled into the liquid phase through the dip tube. The black precipitate disappeared a few minutes after methyl bromide was first introduced. The reaction flask was cooled after all of the methyl bromide had been added. The liquid in the reaction flask was analyzed and contained triethylaluminum (2.5 g, 22 mmol), trimethylaluminum (5.9 g, 82 mmol), and dimethylaluminum bromide (0.63 g, 4.6 mmol).
EXAMPLE 4
This example was conducted in a continuous manner without solvent and with distillation of both trimethylaluminum and ethyl bromide from the reaction flask. The reactor and distillation apparatus were similar to that used in Example 1 except for the following modifications: the reaction flask was fitted with a pressure-equalizing dropping funnel for adding triethylaluminum and the distillation head was fitted with an air-cooled condenser to condense trimethylaluminum and drain it to a collection flask maintained at about 50° C. to prevent alkyl bromide condensation. Non-condensed vapors then passed through the Vigreax column and into a second condenser where the alkyl bromides were condensed.
Under an atmosphere of dry nitrogen, the reaction flask was charged with triethylaluminum (12.0 g, 105 mmol) and then BiCl 3 (2.0 g, 6.3 mmol) was slowly added with stirring. Some "smoke" was observed, the temperature rose to about 55° C., and a black precipitate formed. The flask was heated to 120° C. and then slow feed of 116.8 g of methyl bromide vapor into the stirred liquid phase was commenced. Three minutes later, dropwise feed of 43.1 g (378 mmol) of triethylaluminum was commenced. After another ten minutes, the black precipitate had disappeared. After three hours, all of the triethylaluminum and methyl bromide had been added and the reactor was cooled. Total reactants were 55.1 g (483 mmol) of triethylaluminum and 116.8 g (1.23 mol) of methyl bromide.
The liquid in the reaction flask (51.6 g) separated into two phases. The lower phase (7.2 g) was the catalyst. The upper phase was analyzed and found to contain 22.4 g (197 mmol) of triethylaluminum, 13.6 g (189 mmol) of trimethylaluminum, 0.46 g (3.4 mmol) of dimethylaluminum bromide and other unidentified reaction products.
The liquid in the first receiving flask (7.9 g) was analyzed and found to contain 1.3 g (11.4 mmol) of triethylaluminum, 1.1 g (15 mmol) of trimethylaluminum, 0.077 g (0.56 mmol) of dimethylaluminum bromide, 2.9 g (27 mmol) of ethyl bromide, 0.42 g (3.0 mmol) of butyl bromide (from the butyl content of the triethylaluminum starting material) and other unidentified reaction products.
The liquid in the second receiving flask (73.0 g) was analyzed and found to contain 47 g (430 mmol) of ethylbromide, 26 g (277 mmol) of methyl bromide, and traces of triethylaluminum and trimethylaluminum.
The contents of the first receiving flask and the upper layer from the reaction flask were combined and 86% of the resulting mixture was fractionally distilled to isolate 11.1 g (154 mmol) of trimethylaluminum (isolated yield=71% based on triethylaluminum consumed).
EXAMPLE 5
This example is a continuous reaction similar to Example 4 except that a solvent was used.
Under an atmosphere of dry nitrogen, the reaction flask was charged with BiCl 3 (2.1 g, 6.6 mmol) and n-decane (27 g) after which triethylaluminum (12.6 g, 110 mmol) was added dropwise while stirring, whereupon the reaction temperature rose to about 40° C. and a black precipitate formed. The flask was heated to 120° C. and then slow feed of 132.5 g of methyl bromide vapor into the stirred liquid phase was commenced and the black precipitate began to disappear. Thirty seven minutes later, dropwise feed of 24.0 g (210 mmol) of triethylaluminum was commenced. After about three and one-half hours, all of the triethylaluminum and methyl bromide had been added and the reactor was cooled. Total reactants were 36.6 g (320 mmol) of triethylaluminum and 132.5 g (1.40 mol) of methyl bromide.
The liquid in the reaction flask (53.7 g) separated into two phases. The lower phase (3.6 g) was the catalyst. The upper phase was analyzed and found to contain 18.4 g (255 mmol) of trimethylaluminum, 0.64 g (4.7 mmol) of dimethylaluminum bromide and traces of other unidentified reaction products.
The liquid in the first receiving flask (20.6 g) was analyzed and found to contain 0.23 g (2.0 mmol) of triethylaluminum, 2.7 g (38 mmol) of trimethylaluminum, 0.13 g (0.95 mmol) of dimethylaluminum bromide, 14.8 g (136 mmol) of ethyl bromide, 2.2 g (16 mmol) of butyl bromide (from the butyl content of the triethylaluminum starting material) and traces of other unidentified reaction products.
The liquid in the second receiving flask (108 g) was analyzed and found to contain 65 g (594 mmol) of ethylbromide, 43 g (454 mmol) of methyl bromide, and traces of other unidentified reaction products. | Trimethylaluminum is made by gradually feeding a methyl halide to a reaction vessel containing a tri-C 2+ alkylaluminum (e.g. triethylaluminum) and a catalyst formed from a bismuth compound and an alkyl or aryl organoaluminum compound thereby forming trimethylaluminum and C 2+ alkyl halide and continuously distilling the C 2+ alkyl halide, and any methyl halide that fails to react, from the reaction vessel thereby avoiding the accumulation of trialkylaluminum and alkyl halide which not only tends to form alkylaluminum halides but can be very hazardous on a large scale if a temperature excursion should occur. | 2 |
[0001] This application claims the benefit of U.S. Provisional Patent Application Ser. No. 60/868,948 filed Dec. 7, 2006, the disclosure of which is incorporated herein by reference in its entirety.
BRIEF SUMMARY OF THE INVENTION
[0002] The present invention relates to a novel combination of Glucosamine, Devils' Claw, and S-adenosyl methionine (SAM sometimes calles SAM-e). The dosage form provides greater efficacy than previous combinations of products.
[0003] Glucosamine, the name commonly used for 2-amino-2-deoxyglucose, 2-amino-2-deoxy-beta-D-glucopyranose (C 6 H 13 NO 5 ) is an amino sugar that is an important precursor in the biochemical synthesis of glycosylated proteins and lipids. It has the following structure:
[0000]
[0004] Oral glucosamine is commonly used for the treatment of osteoarthritis. Since glucosamine is a precursor for glycosaminoglycans, and glycosaminoglycans are a major component of joint cartilage, supplemental glucosamine is used to help to rebuild cartilage and treat arthritis. Typical oral dosage is 1500 mg/day.
[0005] Devil's Claw is from the plant Harpagophytum procumbens, also called grapple plant, wood spider, a plant of the sesame family, native to South Africa. It got its name from the peculiar appearance of its hooked fruit. The plant's large tuberous roots are used medicinally to reduce pain and fever, and to stimulate digestion.
[0006] The two active ingredients in Devil's Claw are Harpagoside and Beta Sitosterol. The British Herbal Pharmacopoeia recognises Devil's Claw as having analgesic, sedative and diuretic properties. It has been generally recognized that 50-100 mg/day of Harpagoside as a suggested dosage.
[0007] S-adenosyl methionine C 15 H 24 N 6 O 5 S (SAM) is a biological compound involved in methyl group transfers, and is present in all living cells. SAM is required for cellular growth and repair. It is also involved in the biosynthesis of several hormones and neurotransmitters that affect mood, such as epinephrine.
[0008] It has the following structural formula:
[0000]
[0009] Because of structural instability, stable forms, as known in the art to be forms stable at room temerature over time, including molecular salt forms of SAM are required for its use as an oral drug. Although salt forms have been developed, SAM is still liable to degradation. Therapeutic doses, as practiced in the art, range from 800 mg/day to 1600 mg/day.
[0010] To combine these three substances, it would require a dosage form contining between 2350 mg-3200 mg of active ingredinets not including tableting excipients. This is an amount that would create a very large tablet size that would not be swallowable, or it would require formulation that would require ingesting multiple tablets to achieve the desired effect. It has been discovered that in certain combinations, the therapeutic amount of Glucosamine and SAM can be greatly reduced when certain ratios heretofore not recognized, of all three of these compounds combined into a single dosage form.
[0011] The present invention is a dosage form whereby Glucosamine, DC, and SAM (the ACTIVES)are combined into a single dosage form and the ratio between the ACTIVES create complimentary effects such that the threapeutic level of glucosamine and SAM are reduced.
[0012] This is advantageous because it becomes less expensive to provide the desired therapy and a single dosage form increases patient compliance with the therapy regimen.
[0013] In one embodiment the ratio of DC:Glucosamine:SAM is between 1:1-2:2-3. In a preferred embodiment, the ratio is 1:1.5:2.5. Still another preferred embodiment is 1:1.3:2.25. The increased amount of DC actuates the threrapeutic properties of both Glucosamine and SAM. When the ACTIVES are in combination, they provide for a single dosage form that allows threapy to ocurr at low dosage levels previously not recognized. There are many dosage forms known in the art, and detailed below. A preferred dosage form is a tablet. The amount of Glucosamine required is reduced 60 to 90% of the recognized therapeutic level. In one embodiment, the amount of Glucosamine in the dosage form is present at a level reduced by 75-90% of the recognized therapeutic level. In one embodiment, the amount of SAM is reduced 40 to 85% of the recognized therapeutic level. The reductions in these Glucosamine and SAM amounts allow the ACTIVES to be combined into a single dosage form while still providing the desired therapeutic effect.
[0014] In one embodiment the present invention comprises
[0015] An oral dosage form comprising or consisting of;
(a) Devils Claw; (b) Glucosamine; (c) SAM; in a ratio of (a):(b):(C) of 1:1-2:2-3.
[0020] More preferably the dosage form has ratio of 1:1-1.5:2-2.5. In a preferred embodiment, Glucosamine is present in salt form that may be Glucosamine hydrochloride, Glucosamine sulfate, Glucosamine potassium sulfate, N-acetyl-Glucosamine or other acceptable salts.
[0021] In a preferred embodiment SAM is present in a salt form that may be any sulfate, phosphate, carbonate or other acceptable salts. A preferred salt is the disulfate p-toluenesulfonate.
[0022] The dosage form may be any dosage form acceptable for delivery of a therapeutic substance to a patient. The compositions can be provided in the form of a minicapsule, a capsule, a tablet, an implant, a troche, a lozenge (minitablet), a temporary or permanent suspension, an ovule, a suppository, a wafer, a chewable tablet, a quick or fast dissolving tablet, an effervescent tablet, a buccal or sublingual solid, a granule, a film, a sprinkle, a pellet, a bead, a pill, a powder, a triturate, a platelet, a strip or a sachet. Compositions can also be administered as a “dry syrup”, where the finished dosage form is placed directly on the tongue and swallowed or followed with a drink or beverage. These forms are well known in the art and are packaged appropriately. The compositions can be formulated for oral, nasal, buccal, or transmucosal, delivery, although oral delivery is presently preferred.
[0023] Most preferred is a dosage form that is a tablet or capsule.
[0024] In a preferred embodiment, the dosage form further comprises an enteric coating.
[0025] It is also preferred that the dosage form be provided as a single dosage unit.
[0026] It is an object of the present invention of the present invention to provide therapeutic levels of Glucosamine, DC, and SAM in a single dosage form.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0027] The present invention provides for a dosage form delivering improved therapy of a combination of Glucosamine, DC, and SAM.
[0028] The compositions of the present invention can be processed by agglomeration, air suspension chilling, air suspension drying, balling, coacervation, coating, comminution, compression, cryopelletization, encapsulation, extrusion, wet granulation, dry granulation, homogenization, inclusion complexation, lyophilization, melting, microencapsulation, mixing, molding, pan coating, solvent dehydration, sonication, spheronization, spray chilling, spray congealing, spray drying, or other processes known in the art.
[0029] The composition can be coated with one or more enteric coatings, seal coatings, film coatings, barrier coatings, compress coatings, fast disintegrating coatings, or enzyme degradable coatings. Multiple coatings can be applied for desired performance. Further, the dosage form can be designed for immediate release, pulsatile release, controlled release, extended release, delayed release, targeted release, synchronized release, or targeted delayed release. For release/absorption control, solid carriers can be made of various component types and levels or thicknesses of coats, with or without an active ingredient. Such diverse solid carriers can be blended in a dosage form to achieve a desired performance. The definitions of these terms are known to those skilled in the art. In addition, the dosage form release profile can be affected by a polymeric matrix composition, a coated matrix composition, a multiparticulate composition, a coated multiparticulate composition, an ion-exchange resin-based composition, an osmosis-based composition, or a biodegradable polymeric composition.
[0030] The term “enteric coating” as used herein relates to a mixture of pharmaceutically acceptable excipients that is applied to, combined with, mixed with or otherwise added to the carrier or composition. The coating may be applied to a compressed or molded or extruded tablet, a gelatin capsule, and/or pellets, beads, granules or particles of the carrier or composition. The coating may be applied through an aqueous dispersion or after dissolving in appropriate solvent. Alternatively, an enteric coating may be applied in an aqueous/organic cosolvent system. Additional additives and their levels, and selection of a primary coating material or materials will depend on the following properties: 1. resistance to dissolution and disintegration in the stomach; 2. impermeability to gastric fluids and drug/carrier/enzyme while in the stomach; 3. ability to dissolve or disintegrate rapidly at the target intestine site; 4. physical and chemical stability during storage; 5. non-toxicity; 6. easy application as a coating (substrate friendly); and 7. economical practicality.
[0031] Cellulose Derivatives are a preferred enteric coat material. Examples of suitable cellulose derivatives are: ethyl cellulose; reaction mixtures of partial acetate esters of cellulose with phthalic anhydride.
[0032] A preferred coating is aqueous Ethylcellulose Dispersion. The dispersion is a combination of film-forming polymer; plasticizer and stabilizers. Designed for sustained release and taste masking applications, the dispersion provides the flexibility to adjust drug release rates with reproducible profiles that are relatively insensitive to pH.
[0033] The principal means of drug release is by diffusion through the dispersion membrane and is directly controlled by film thickness. Increasing or decreasing the quantity of dispersion applied can easily modify the rate of release.
[0034] Two well-known dispersions are Surelease (Colorcon, West Point, PA) and Aquacoat ECD (FMC).
[0035] The performance of a coating can vary based on the degree and type of substitution. Cellulose acetate phthalate (CAP) dissolves in pH>6. Aquateric (FMC) is an aqueous based system and is a spray dried CAP psuedolatex. Other components in Aquateric can include pluronics, Tweens, and acetylated monoglycerides; cellulose acetate trimellitate (Eastman); methylcellulose (Pharmacoat, Methocel); hydroxypropyl methyl cellulose phthalate (HPMCP). The performance can vary based on the degree and type of substitution. HP-50, HP-55, HP-55S, HP-55F grades are suitable; hydroxypropyl methyl cellulose succinate (HPMCS; AQOAT (Shin Etsu)).
[0036] The coating can, and usually does, contain a plasticizer and possibly other coating excipients such as colorants, talc, and/or magnesium stearate, which are well known in the art. Suitable plasticizers include: triethyl citrate (Citroflex 2), triacetin (glyceryl triacetate), acetyl triethyl citrate (Citroflec A2), Carbowax 400 (polyethylene glycol 400), diethyl phthalate, tributyl citrate, acetylated monoglycerides, glycerol, fatty acid esters, propylene glycol, and dibutyl phthalate. In particular, anionic carboxylic acrylic polymers usually will contain 10-25% by weight of a plasticizer, especially dibutyl phthalate, polyethylene glycol, triethyl citrate and triacetin. Conventional coating techniques such as spray or pan coating are employed to apply coatings. The coating thickness must be sufficient to ensure that the oral dosage form remains intact until the desired site of topical delivery in the lower intestinal tract is reached.
[0037] Colorants, detackifiers, surfactants, antifoaming agents, lubricants, stabilizers such as hydroxy propyl cellulose, acid/base may be added to the coatings besides plasticizers to solubilize or disperse the coating material, and to improve coating performance and the coated product.
[0038] A coating process frequently involves spraying a coating solution onto a substrate. The coating solution can be a molten solution of the encapsulation coat composition free of a dispersing, medium. The coating solution can also be prepared by solubilizing or suspending the composition of the encapsulation coat in an aqueous medium, an organic solvent, a supercritical fluid, or a mixture thereof. At the end of the coating process, the residual dispersing medium can be further removed to a desirable level utilizing appropriate drying processes, such as vacuum evaporation, heating, freeze drying, etc.
[0039] Solvent-based coating is when the components of the invention are solubilized and/or dispersed in a solvent. The solvent can be aqueous. When the solvent is aqueous-based, the components can be emulsified with an appropriate emulsifier, organic solvent, or a supercritical fluid. Solvents with a lower melting point than water and higher evaporation numbers are preferred. Solvent mixtures with other organic solvents or water are often employed to get appropriate viscosity and component solubilization. Typical solvents include ethanol, methanol, isopropanol, acetone, dichloromethane, trichloromethane and ethyl acetate. Appropriate polymers can also be added as needed. Cellulosic derivatives and polymethacrylates are particularly suitable additives for organic solvent coating. Dissolution and solubilization of the components is facilitated by rigorous stirring or heating. Plasticizers may be also be added to stimulate dissolution. Colorants and antisticking agents can be employed as needed.
[0040] The following are presented by way of example and are not intended to limit the scope of the invention.
[0041] One general formulation is as follows:
[0000]
Glucosamine
5-25%
DC
3-15%
SAM
10-40%
Filler
20-75%
Binder
1-20%
Disintegrant
up to 15%
Lubricant
up to 10%
Glident
up to 10%
EXAMPLE 1
[0042] In one embodiment a first blend comprising 100 g DC, 200 g Glucosamine, and 300 g of SAM are passed through a 25 mesh screen and blended until uniformly mixed. A second blend is prepared comprising 400 g microcrystalline cellulose (a common form sold as AVICELO by FMC, Philadelphia, Pa.),
[0043] 54 g stearic acid, and 8 g croscarmellose sodium are each passed through a 25 mesh screen. The first and second blends are combined in a v-blender and mixed 45 minutes or long enough to ensure content uniformity as is commonly known and practiced in the art. The blender is stopped and 15 mg of silicon dioxide and 15 mg of magnesium stearate are screened through a 25 mesh screen and added to the blender. The mixture is blended an additional five minutes. The tableting mixture is discharged from the blender. Capsule shaped tablets with a target weight of 1300 mg (±6%) are compressed with a target hardness of 10-15 kP.
[0044] Tablets prepared according to Example 1 may optionally be coated with a layer. Alternatively, the tablets may be coated with more than one layer. Any layer may be functional or non-functional and may include, but would not be limited to controlled release, delayed release, sustained release, color, taste masking, moisture barrier, or any other layer disposed on the surface as are commonly practices in the art. In a preferred embodiment, the tablets are coated with an enteric layer such that they do not dissolve in the gastric pH of approximately 1.2.
[0045] While the invention has been described in its preferred form or embodiment with some degree of particularity, it is understood that this description has been given only by way of example and that numerous changes in the details of construction, fabrication, and use, including the combination and arrangement of parts, may be made without departing from the spirit and scope of the invention. | The present invention is a composition delivering effective amounts of Glucosamine, Devils Claw, and SAM in a single dosage unit. | 0 |
OBJECT OF THE INVENTION
[0001] The present invention refers to a device for exercises, sports, gymnastics and various activities that join Eastern and Western techniques, concepts, and theories related to exercise, sports and health.
ANTECEDENTS OF THE INVENTION
[0002] At the present time western health culture is based, in large part, on the elimination of stress, the fulfilment of prevention exams, the maintenance of healthy nutrition, and actively, the practice of exercise and gymnastics.
[0003] Especially in the West, this kind of exercise or gymnastics practice is focused on three areas: muscular exercise, aerobic exercise (cardiovascular), and stretching.
[0004] On the other hand, eastern health culture gives equal significance to the body, mind, emotions and spirituality in addition to integrating all of them, the (body, mind, and soul), toward this end using concepts, theories, techniques and skills like traditional Chinese medicine, Tai Chi Chuan, Qigong or Yoga, in which the balance between body, mind and spirit, is intended with a sense of aesthetic and an energy interchange in order to achieve the balance between Ying and Yang which provides peace and health. These concepts, theories and arts are applicable to any kind of sport, exercise or daily activity.
[0005] The device of the present invention intends, therefore, to facilitate, improve and optimize the practice of exercises, sports, gymnastics or other activities (calligraphy, dance, and theatre, among others) by joining concepts and theories of both cultures and by providing the individual that uses the device with the advantages of both cultures, as it is not currently known that any other devices would serve the same purpose.
DESCRIPTION OF THE INVENTION
[0006] The device of the present invention is for the practice of exercises that joins techniques, concepts and theories of the West and of the East in relation to exercise, sports and health; that joins the western gymnastics technique that focuses on muscular exercise, aerobics, and stretching with the eastern technique which works properly with relaxation, concentration, breathing, and the corporal position, as well as biodynamic and energetic flow; combined with the stimulation of the acupunctural and energetic channels of the body and of the groin area, the meditation in motion and the promotion and development of the “Dan Tien” (energetic Centre developer of strength and gravity of the body situated beneath the navel).
[0007] The device is used by means of specific exercises, or during the development of any kind of activity, sport or exercise; achieving a greater training for muscular and aerobic strength, a better comprehension of the centre of gravity and the development of strength in the user situated at the lower abdomen, a coordination between the lower and higher parts of the body as well as of the upper and lower limbs and an integration of the whole body, physically and emotionally for better performance and use of training time, as well as the activation of energetic centres, channels and meridians. All of the above functions as facilitated by the device, improve the performance of the specific activity or sport engaged in as well as the health, well-being, and physical and psychological equilibrium of the user.
[0008] In addition, the device of the present invention can be used in conjunction with the practice of any kind of sport or activity of western or eastern inspiration. Examples of such sports and activities include aerobics, step, walking, jogging, golf, baseball, tennis, disco, weight, javelin, dance, aquatic, martial arts: Karate, Kung Fu, Tae Kwon Do, Judo, Tai Chi Chuan, Aikido, boxing and so forth.
[0009] According to the invention, the device comprises a belt that is firmly adjusted to the user's waist in the abdomen region, which helps to avoid inguinal hernia, protects the lumbar zone, and creates a consciousness of the middle torso area, which is indispensable to promote during the performance of the exercise or practice facilitating the development of inherent benefits, for example, greater strength, among other things.
[0010] The belt of the device comprises a component for the sliding passage of two straps at the center of gravity of the user, which is the strength-generating and energy-interchanging zone of the lower abdomen. The ends of the straps are fixed to the extremities of the user, preferably at the ankles and wrists, to facilitate coordinated movement.
[0011] The movement of the straps through the sliding component can be blocked to achieve the independent exercise of the user's extremities.
[0012] The straps are elastic and are adjustable in length in order to adapt to the size of the user or to the exercise or sport to be practiced. As a result, the stretching of the straps during exercise or the activity is possible regardless of whether the sliding component, situated at the belt, is blocked or not; consequently, the extremities can be either independent from or related to each other.
[0013] The straps will be fastened to the users extremities in a comfortable fashion. All the materials used that are in contact with the skin are hypoallergenic and preferably natural.
[0014] There are several functional possibilities of the device depending on different combinations in arrangement of the straps with regard to each of the extremities and depending on the different objectives and benefits to be achieved. One of these possibilities consists in crossing the straps relating the inferior left extremity (ankle) with the superior right one (wrist), and vice versa with the other strap. The device functions as well without crossing the straps by relating the superior and inferior extremity of the same side with each of the straps. Another possibility consists in connecting with one strap the inferior extremities and with the other strap the superior ones. Further, another possibility, as mentioned before, consists of immobilizing the straps in order to make the extremities independent during exercise. The preferred way of using the straps of the invention involves placing the sliding passage component at the front part of the body, although it can also be used on the back side of the body as well at the same height as the torso level previously mentioned, thereby with the strings passing through the back side of the body (behind the torso—back—and behind the and legs).
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] FIG. 1 shows a view of a preferred embodiment of assembly of the device of the present invention.
[0016] FIG. 2 shows the details of the casing for the sliding passage component of the straps for the device of the present invention.
[0017] FIG. 3 shows a schematic lateral view of the sliding passage component of the straps for the device of the present invention.
[0018] FIG. 4 shows a detailed view of the extremities of the straps, the curl and the hook to which a small cushion is fixed.
[0019] FIG. 5 shows a detail of one of the small cushions that are fixed to the limbs of the user.
[0020] FIG. 6 shows another preferred embodiment of assembly of the device of the present invention.
[0021] FIG. 7 shows a detail of the casing for the sliding passage component of the straps for the device of the present invention according to the assembly shown in FIG. 6 .
[0022] FIG. 8 shows a schematic lateral view of the casing of the sliding passage component for the straps of the device of the present invention according to the composition shown in FIG. 6 .
DESCRIPTION OF ACCOMPLISHED PRACTICES OF THE INVENTION
[0023] The device 1 of the invention comprises a belt 2 preferably around 4 cm wide, which is adjusted to the user's waist beneath the navel, and is provided with a belt buckle 3 and buttonholes 4 to be adjusted at a maximum. The belt is preferably composed of natural hypoallergenic materials, for instance leather.
[0024] On the belt, in the area of the lower abdomen, a piece 5 of sliding passage component which can be optionally blocked is fixed, for two elastic straps 6 that extend at their ends in curls 7 provided with hooks 8 for detachably fixing with the removable small cushion 9 which can be fastened to the ankles and wrists of the user. There is an economical way of producing the invention in which the hooks are not required when the cords are directly fixed to the small cushion.
[0025] The thickness of the straps 6 can vary, and can vary from approximately 7 to 12 millimetres, with a length of approximately 1.80 metres. The thickness of the straps will influence their elasticity and therefore the level of training, allowing for higher or lower muscular and aerobic training, as well as other characteristics of the invention
[0026] The length of the straps is adjustable so that the straps can adjust to the size of the user and also influence the training effort by a lengthening or shortening of the straps. The adjustment is made by means of buckles 10 which also define the ends of corresponding curl 7 .
[0027] On the other hand, the small cushions 9 are made up of natural and hypoallergenic materials, preferably incorporating a soft stuffing which minimizes the traction made by wrists and ankles. These small cushions integrate a belt 11 to be fixed to the joint by an adhesive (fastener) base, and a ring 12 on which is fixed the corresponding hook 8 , or directly the corresponding curl at the end of the cord.
[0028] Piece 5 is made up of a case 13 internally threaded with a blind bottom 5 a , projecting out perpendicularly of the external side 14 of the belt. This case is provided with holes 15 on the perimeter for an easy passageway for the straps 6 , which will be able to slide freely through them and on some channels 5 b inserted in the blind bottom of the case which assist in their movement. Threading till the end a threaded piston rod 16 , will strangulate the straps impeding their movement through the interior of the case, the straps will be immobilized, as they are trapped against the bottom of the channels 5 b ; or loosening the threaded piston rod a bit without removing it completely will permit the free movement of the straps for use with the various techniques previously mentioned.
[0029] The case will preferably have four holes on the same level with regard to its axis, situated close by pairs in a lower and upper sense and with the straps sliding in this instance in parallel through the interior of the case. In the situation they cross each other, they will do so at the upper exterior part of the case as shown in FIGS. 1 and 2 .
[0030] In another preferred embodiment of assembling the invention, the peripheral holes are situated in two levels with respect to the axis of the case, with two holes brought face to face diametrically in less depth and four holes brought face to face diametrically two against two, out of phase 90°, correspondingly with two of them projected against the other two situated in less depth as shown in FIGS. 6 and 7 . In this last instance the straps can cross each other at the interior of the case in a coplanar way or at different depths.
[0031] Having sufficiently described the nature of the invention, as well as the way to put it in to practice, it should be taken into account that the dispositions previously indicated and represented in the attached drawings are susceptible to modification of details on the condition that the fundamental principle will not be altered. | Device for practicing exercises, sports, gymnastics and different physical activities, which join various techniques and concepts of eastern and western theories related to exercise, sports, and health; such a device comprising of a belt adjustable to the abdomen region of the user, which incorporates a sliding component with an optional blocking system to be crossed by two elastic straps of adjustable length, each strap having at the end a removable fastening system for the extremities of the user. | 0 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a method of controlling the interfacial adhesion between a metal or alloy and an organic material, and to a structure produced thereby.
More particularly, this invention relates to a method of controlling the interfacial adhesion between one material, such as a metal or alloy, and another material, such as an organic material which has an affinity for absorbing water, water vapor or for absorbing or being degraded at the surface by any other fluid or solvent, and the coherent product formed thereby.
Most particularly, this invention relates to a method for improving the interfacial adhesion between a metal or alloy, particularly a film comprising chromium or chromium overlaid with copper, and a film comprising polyimide (PI). It also improves the polymer-to-polymer bond in a laminate structure. This invention relates also to the product formed as a result of the method, and the machine by which the product is produced.
The method, product and machine of the invention are particularly useful in the electronic packaging art, wherein polyimide films and coatings have potential as a flexible dielectric carrier, on which is disposed conductive circuitry, on which are in turn optionally disposed one or more of intergrated circuit chips and/or surface mounted components.
2. Background Art
Certain organic materials, particularly certain polyimides, are promising from many points of view for use as flexible film insulative carriers in electronic packaging applications such as, for example, in flexible and Tape Automated Bonding (TAB) configurations. Being flexible, polyimide is easy to handle and its coefficient of thermal expansion (CTE) is close to that of silicon, a fact which is convenient when connection is made between electronic chips and polyimide carriers. The coefficient of linear expansion of polyimide (2×10 -5 in/in degree C) is one of the best among polymers supplied in a roll format. Other properties of PI that make it useful for the electronics industry are its dielectric strength (5,400 volts/0.001 inch typical for 0.002 inch thick), its dissipation factor (0.0025 for 0.002 inch thick), its volume resistivity (8×10 15 ohm meters for 0.002 inch thick and 125 volts). However, the affinity of polyimide to absorb moisture creates a number of difficulties involved in its use, such as unreliable short and/or long-term adhesion between the polyimide and the conductive lines disposed thereon.
In the short term, additional processing steps subsequent to the initial deposition of metal-on-polyimide, such as steps related to additive electroplating, expose the polyimide to chemical solutions and solvents which are absorbed by the polyimide and provide a cause for lifting of the conductive lines. In the long term, a failure in the line adhesion due to temperature and humidity effects on a working device is intolerable in the high performance computer systems of the future, for which absolute reliability is necessary. Whereas the flexible film carrier with surface mounted chip or other device is a configuration which reduces problems due to thermal mismatch between the chip and the support on which the chip is mounted, the problem of adhesion between the metal and non-metal portions of the carrier has not been fully resolved.
It is known that polyimide absorbs about 3-4% by weight of water. However, exposure to water is unavoidable, as water is used in cleaning dust and debris as is caused by mechanical punching. Exposure to a humid working environment cannot always be avoided. In addition, the polyimide is exposed to water solutions of electrolytes in the additive plating process. When polyimide is exposed to an electrolyte, conductive ions from the solution are absorbed with solute, damaging the dielectric properties as well as the adhesive capability of the polyimide. In U.S. Pat. No. 4,863,808 issued Sep. 5, 1989 to Sallo, the vacuum deposition of chromium as a barrier layer between copper and polyimide is described as affording resistance to undercutting by subsequent gold and tin plating baths. Applicants have found that the use of a chromium layer is not alone sufficient protection for polyimide.
Studies have proposed the role of carbonyl formation on adhesion promotion between metal and polyimide. There are basically two interpretations of the interaction between polyimide and a metal atom.
In the first approach, described in the IBM Journal of Research and Development, 32,658 (1988), by Ho et al., the formation of a charge transfer complex between the incoming metal atoms and the aromatic ring of the PMDA portion of the molecule is proposed. Quantum mechanical calculations suggest that the interaction above described is more important than the chromium-carbonyl group interaction.
In the second proposed interaction, described by Gold berg et al. in the Journal of Vacuum Science Technology, A6,991 (1988), the authors describe the attack of the first Cr atoms on the PMDA portion of the polyimide structure. As a consequence of such an attack, the first Cr atoms become oxidized while the PMDA portion of the PI molecule becomes reduced to a mono-anion. Interaction of the carbonyl groups with the Cr ion induces formation of Cr-O bonds. The first interaction involves a Cr ion with two carbonyl groups from different chains. Additional Cr deposition leads to formation of more Cr-O and Cr-N bonds.
The latter explanation applies to other metal/PI interactions besides Cr/PI. With an increased population of carbonyl groups, much greater interaction and better adhesion strength is expected at the metal/PI interface. This is why carbonyl group enhancement via oxygen plasma treatment may be expected to affect the adhesive quality of material produced.
However, the art neither describes nor suggests that the problem of adhesion between chromium and polyimide is solved by control rather than elimination of the water content of the polyimide, and the art does not describe or suggest the process steps, structure or device of the present invention. The art does not account for the fact that adhesion between metal and organic material does not simply bear a directly proportional relationship to the amount of carbonyl exposure, but actually diminishes beyond an optimum time of exposure.
The present inventors have made the surprising discovery that the removal of all water from the polyimide is neither necessary nor desirable, and that a small residual amount of moisture can actually enhance adhesion between the metal and non-metal to an extent not heretofore seen or expected.
Sputter roll metallizers are known in the art. However, in the systems known in the art, the oxygen DC glow chamber is found at the chill drum section. The sputter roll metallizer of the present invention is set inline apart from the DC glow chamber, allowing increased oxygen pressure.
SUMMARY OF THE INVENTION
It is therefore an object of the invention to provide a flexible film carrier having a controlled degree of adhesion between the polyimide base and the circuitization layers.
It is a further object of the invention to provide a flexible film carrier having improved short and long-term adhesion between the polyimide base and the circuitization layers which is superior to that known in the art.
It is a further object of the invention to provide a flexible film carrier with improved imperviousness to moisture whether in gas or liquid form.
The foregoing and other objects and advantages are accomplished in the present invention by means of process steps which include partial outgassing of water from the polyimide carrier at an elevated temperature to a predetermined, near zero level prior to surface treatment with energetic oxygen atoms. The process is performed in situ, optionally either in a vacuum sputter, cooled-roll system or as a panel process. The process leaves detectable "footprints" in the product which can be detected by Rutherford Backscattering (RBS).
BRIEF DESCRIPTION OF THE DRAWINGS
Table I shows adhesion values in grams per millimeter for a 0.3 mil thick conductor line to polyimide for two sets of conditions, both by means of the present invention and by means known in the art.
Table II shows the effect of web speed on metal-to-polyimide adhesion in a roll system.
Table III shows the effect of web speed in the roll process on the adhesion to polyimide of a 0.3 mil thick copper line.
Table IV shows the effect of web speed in the roll process on the adhesion to Dupont 712 polyimide at 100 ft./hr. plasma of a 0.3 mil thick copper line as compared to on Dupont 713 polyimide at twice the speed.
FIG. 1 shows the carbon-1 spectrum (C1S) Electron Spectroscopy for Chemical Analysis (ESCA) from the downstream oxygen microwave plasma process.
FIG. 2 shows the C1S ESCA from a typical oxygen plasma. FIG. 3 is a flowchart of the sputter seed process of the invention, so called because the chromium-copper flash provides a continuous metallization for subsequent additive electroplating.
FIG. 4 is a schematic drawing of the sputter roll metallizer of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
In order to facilitate understanding of the present invention, reference is made to the following detailed description taken in conjunction with the above described tables and figures.
It has been thought that complete removal of water from polyimide is a requirement for providing adhesion between metal and for providing strong polymer-to-polymer bonding, and that once it is completely removed, keeping the water out is a requirement for maintaining adhesion over time. It has also been thought that high temperature treatment is required in order to obtain this result. The present invention includes a process, a device for carrying out the process, and a resulting metallized organic structure in which extremely high values of adhesion, the highest known, are exhibited between the non-metallic and metallic portions of the structure. In order to obtain the enhanced adhesion values it has been surprisingly discovered that it is neither necessary nor desirable to remove all absorbed water from the organic component, described herein as polyimide. In fact, thorough outgassing of all water at high temperature actually results in reduced adhesion over the present method and in heat creasing of the organic component during metallization. Under outgassing conditions which result in reduction of the water absorbed in the polyimide to a level estimated at about 1% to about 2% by weight and under conditions of moderate temperatures adhesion is enhanced. Furthermore, polyimide that is "bad" i.e. varies in its properties, can be made to form an adherent bond to metal reproducibly by means of the present invention.
The examples below are representative of the conditions for which the values in Table I were obtained.
EXAMPLE 1
The shiny side of a roll of Dupont Kapton H-film polyimide (a/k/a web) was passed through a vacuum interlock into the vacuum roll sputter system of FIG. 4 at a rate of 400 feet per hour and partially outgassed in vacuum at 250 degrees C. for 8 seconds. Unlike the roll metallizers which are commercially available, the roll metallizer of FIG. 4 does not have the oxygen DC glow chamber at the chill drum section. As seen in FIG. 4, the oxygen DC glow chamber of the present invention is characterized by being set similar to an inline configuration. This permits attainment of an oxygen pressure of 70×10 -3 torr. This pressure is about 10 times higher than that of a conventional roll metallizer in which the glow unit is located at the drum. Having the glow discharge at the drum places it in close proximity to the sputter targets which requires that the glow pressure be kept low for minimizing oxygen contamination of the sputtered metals. The 250 degrees C. temperature was maintained/monitored. Next the polyimide was sputter coated with a strike layer of about 250 Angstroms chromium followed by a layer of about 6,000 Angstroms sputtered copper. The vacuum was maintained throughout completion of all steps. The overall vacuum process is seen in the flow chart, FIG. 3. The web was electroplated in a commercially available copper electroplating bath up to a thickness of 0.3 mils. Lines were formed subtractively, i.e. by photolithographically coating copper in areas to be protected and dissolving the uncoated copper, and the adhesion of the lines was evaluated by use of the the standard 90 degree peel test in conjunction with accelerated environmental stressing in a temperature-and-humidity chamber for 1000 hours at 85 degrees C. and 80% relative degrees C. and 80% relative humidity, a test commonly used for evaluating adhesion which is deemed to equate to ten years' use in a computer. Five lines were tested in order to obtain the 5.6 g./mm adhesion-value seen in Table I, with a standard deviation of less than 5%.
EXAMPLE 2
The same procedure was followed as described in Example 1, except that subsequent to the step of partial outgassing of water from the polyimide web and prior to the step of chromium deposition, the surface of the polyimide web was subjected to energetic oxygen atom treatment at 200 ft./hr. This additional plasma step was performed in situ, without breaking vacuum either before or after the plasma step. The line adhesion measured 61.8 g./mm.
EXAMPLE 3
The same procedure was followed as described in Example 2, except that instead of 250 degrees C. the temperature of the heater was maintained at 150 degrees C. The resultant line adhesion measured 43.3 g./mm.
The experiments described in Examples 1-3 show that for a web speed of 400 ft./hr. an oxygen plasma of 200 ft./hr. in combination with a heater temperature above 150 degrees C., in fact at about 250 degrees C., results in greatly improved adhesion of the metal lines to the non-metal carrier which, in the three examples, was 0.3 mil electroplated copper lines over a chrome-copper strike layer on polyimide.
Besides the Kapton H polyimide in the 3 examples, other polyimides which can be used with substantially similar results include Kapton V, UBE Upilex `S` and `R`, Kanegafuchi Apical `AV` and Mitsubishi Novax. Dupont H Kapton in 0.005 in. and 002 in. thicknesses and VBE Upilex S in 0.002 inches were tested reproducibly.
The high oxygen atom energy treatment step can be performed by placing the web in an RF plasma, DC glow or Ion Beam for a short time, but the oxygen atoms must be of sufficient energy to effect the chrome-polyimide interaction.
As can be seen in Table II for microwave generated plasma, increasing the treatment time (slower web speed) has a deleterious effect on adhesion values, contrary to what would be expected. Whereas it is known that the downstream plasma process creates oxygen atoms, which cause the formation of carbonyls on the polyimide surface, the art theorized that the improvement in adhesion was was directly proportional to the concentration of carbonyls on the polyimide surface. The results in Table II indicate that the direct proportionality is not so beyond a certain point. In addition, the ESCA curves of FIGS. 1 and 2 indicate no difference. In other words, no difference is shown between the ESCA spectrum taken from the downstream microwave plasma process (FIG. 1) and that of the typical oxygen plasma (FIG. 2).
Table III shows the adhesion values in g./mm at various web speeds, i.e. exposure times, when the Dupont H 712 Kapton is treated with an oxygen DC glow rather than the downstream microwave plasma of Table II. As in Table II the temperature was 250 degrees C. and the metal lines 0.3 mils thick. Table III indicates that adhesion increases to a maximum at a specific oxygen treatment time, namely at or about 100 ft./hr., and then decreases. This result is in contrast to the teachings in the art, which would lead one skilled in the art further to increase treatment time in order to maximize adhesion, and supports the high energy specific, controlled dosage times of the present invention.
Table IV shows the adhesion values in g./mm at web speed of 100 ft./hr. for Dupont 712 polyimide and 200 ft./hr. for Dupont 713 polyimide, the temperature in both cases being 250 degrees C. and the metal lines 0.3 mils thick. A comparison with Table III indicates that the result for
Dupont 712 H polyimide is reproducible at 100 ft./hr. and that at 200 ft./hr. Dupont 712 polyimide exhibits adhesion superior to Dupont 713 polyimide at the same oxygen DC glow exposure.
In all the above examples it is necessary that once the outgassing and plasma steps are complete, Cr and Cu must be sputtered in situ. Breaking vacuum between the plasma and the Cr deposition steps resulted in poor adhesion between the metal and the polyimide; breaking vacuum between the Cr and Cu deposition steps resulted in Cr-to-Cu delamination. The vacuum system used must contain a heater section, a plasma section, and a metal deposition section.
It is not necessary that the polyimide be in roll form for the process of the invention to result in the improved adhesion. Likewise, the process is potentially applicable to organic materials other than polyimide and to metal layers other than Cr-Cu-Cu. It is understood that the invention may be embodied in modifications of the present invention forms without departing from the spirit or central characteristics thereof. The aforementioned examples and embodiments are therefore to be considered in all respects as illustrative rather than restrictive, and the invention is not to be limited to the details given herein.
TABLE I__________________________________________________________________________ADHESION VALUES FOR A 0.3 MIL THICK LINE, VALUES ING/MM, 5 LINES PER VALUE AND STANDARD DEVIATIONOF <5%, SHINY SIDE 400'/hr. WEB SPEED 400'/hr. WEB SPEED400'/hr. WEB SPEED 250 C HEATER TEMP. 150 C HEATER TEMP.250 C HEATER TEMP. 200'/hr. PLASMA 200'/hr. PLASMA__________________________________________________________________________5.6 61.8 43.3__________________________________________________________________________
TABLE II______________________________________MICROWAVE GENERATED PLASMA LOCATEDDOWNSTREAM FROM MATERIAL VALUES AREIN G/MM FROM A 0.3 MIL THICK Cu LINE25'/hrWEB 100'/hr. 200'/hr. 400'/hrSPEED WEB SPEED WEB SPEED WEB SPEED______________________________________0 4 13 21______________________________________
TABLE III______________________________________02 DC GLOW TREATMENTS WITH 400'/hr, 250° C.OUTGASSING PROCESS VALUES ARE IN G/MMFROM A 0.3 MIL THICK Cu LINE25'/hr 100'/hr. 200'/hr.WEB SPEED WEB SPEED WEB SPEED______________________________________18.2 67.4 61.8______________________________________
TABLE IV______________________________________02 DC GLOW TREATMENT WITH 400'/hr, 250° C.OUTGASSING PROCESS VALUES ARE IN G/MMFROM A 0.3 MIL THICK Cu LINEDuPont 712 DuPont 713100'/hr. Plasma 200'/hr. Plasma______________________________________67.4 43______________________________________ | The adhesion of chromium-copper layer to polyimide has been greatly improved by a method which provides controlled reduction, rather than total elimination, of water content in the polyimide. The electronic packaging device which incorporates the flexible circuit prepared by the method exhibits greatly improved reliability. It is believed that the invention can be used to improve the adhesion between other organic materials having moisture affinity and materials comprising in-organics or between two organic materials. | 1 |
BACKGROUND OF THE INVENTION
The present invention relates to a sheet feeding apparatus for a printing press, a punching machine or the like, for feeding sheets of paper one at a time from a stack of the sheets to a printing or punching unit, and more particularly to an automatic mechanism for loading a new stack of sheets.
A typical conventional paper sheet feeding apparatus comprises a main lift for elevating a pallet upon which is placed a stack of paper sheets to be fed to a printing press, a punching machine or the like. A sheet separator is installed over the stack of sheets which has been elevated to a predetermined position, to separate the uppermost sheet one by one. When the sheets of the stack have been fed considerably, a new stack of sheets must be loaded. In the known art, the loading of a new stack is carried out by manually inserting a plurality of parallel spits under the old stack of sheets, which has been consumed considerably, to support the old stack from below, and the main lift is lowered to receive the new stack of sheets thereon. The parallel spits are supported in cantilever fashion by an auxiliary lift.
The lowered main lift supporting the new stack of sheets thereon is then elevated until the uppermost sheet of the new stack is brought into abutment with the undersides of the spits. Thereafter, the spits are retracted so that the old stack which has been supported by the spits is placed on the new stack.
In the conventional paper sheet feeding apparatus described above, the spits extend and are advanced and retracted in the direction of feed of the sheets. When these spits are supporting the old stack, they deflect downwardly due to the load of the stack. It will be understood that the downward deflection of the spits is increased toward the tip ends thereof since the spits are supported by the auxiliary lift in cantilever fashion. This is undesirable because the stack of sheets supported by the spits are caused to have an upper surface inclined downwardly in the direction of feed of the sheets, as the surface extends from its position over the proximal ends of the spits to its position over the tip ends thereof, and because the sheet separator fixed at a predetermined position over the stack of sheets has different relative position relative to the uppermost sheet of the stack in the direction of feed the sheets. It will be apparent that this affects adversely to the sheet separating function of the sheet separator as well as to the sheet feeding operation, as will be described hereinafter in more detail, and that this necessitates readjustment of the position of the sheet separator as well as skill of the operator during the operation of the sheet feeding apparatus.
The present invention was made to solve the above and other problems encountered in the conventional sheet feeding apparatus and has for its object to provide an automatic sheet stack loading mechanism of a sheet feeding apparatus wherein the downward deflection of the stack of sheets does not adversely affect the sheet separating and feeding operation.
SUMMARY OF THE INVENTION
According to the present invention, the object stated above is attained by an automatic sheet stack loading mechanism of a sheet feeding apparatus, comprising a main lift for supporting thereon a stack of sheets to be fed, a sheet separator disposed over the main lift to act on the uppermost sheet of the stack of the sheets so as to separate the sheets one by one from the stack, said main lift being movable upwardly to bring the uppermost sheet of the stack thereon to a predetermined height position relative to the sheet separator, and horizontally extending parallel spits for insertion under the stack of sheets supported by the main lift to support the load of the stack from below thereby to enable the main lift to be lowered to receive a new stack of sheets thereon while the uppermost sheet of said first mentioned stack is held at said predetermined height position, said mechanism being characterized by comprising a pair of vertically movable carriage means disposed at both sides of the main lift with respect to the direction transverse to the direction of feed of the sheets from said first mentioned stack, each of said carriage means carrying thereon the parallel spits in such a manner that the spits extend in said transverse direction and are shiftable toward and away from the stack on the main lift, and motive means for shifting the spits toward and away from the stack on the main lift.
According to the present invention, downward deflection of the stack of sheets supported on the spits occurs along the central portion of the sheets in the direction of feed of the sheets, and the deflected central portion is not inclined and is held at a constant height with respect to the direction of the feed of the sheets. For this reason, it is not necessary to adjust the height of the sheet separator, and the feed of sheets is made in good order.
A preferred embodiment of the present invention will be described below with reference to the accompanying drawings.
BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS
FIG. 1 is a fragmentary front view, partly in section, of a preferred embodiment of a sheet stack loading mechanism of a sheet feeding apparatus in accordance with the present invention;
FIG. 2 is a front view illustrating the major component parts thereof;
FIG. 3 is a perspective view illustrating major component parts thereof;
FIG. 4 is a perspective view illustrating a sheet pressing device used in the preferred embodiment shown in FIGS. 1-3;
FIG. 5 is a schematic perspective view illustrating a general arrangement of the sheet feeding device used in the preferred embodiment of the present invention;
FIGS. 6A to 6J are diagrammatic views for explaining the successive steps of operation of the preferred embodiment;
FIG. 7 is a fragmentary sectional view, on an enlarged scale, illustrating exaggeratedly withdrawal of a spit for supporting a stack of sheets;
FIG. 8 is a schematic side view of a conventional sheet feeding apparatus;
FIG. 9 is a perspective view illustrating the manner of loading a new stack of sheets in the apparatus shown in FIG. 8; and
FIG. 10 is an exaggerated side view illustrating the state of supporting a stack of sheets by spits in the conventional apparatus shown in FIG. 8.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Prior to the detailed description of the present invention, a typical conventional paper sheet feeding apparatus will be described for better understanding of the advantageous features of the present invention in comparison with the conventional apparatus.
As shown in FIG. 8, the typical conventional paper sheet feeding apparatus for printing presses, punching machines or the like comprises a main lift 3 for vertically moving a drain-board-like pallet 2 (having multiple parallel grooves in the upper surface) upon which is placed a stack 1 of paper sheets; a sheet separator 4 including vacuum suction pads 4a and 4b and an air blowing pipe 4c for separating the uppermost paper sheet from the stack 1 of sheets and for feeding the separated paper sheet in the direction indicated by an arrow A; an elevator mechanism (not shown) for upwardly moving the main lift 3 in such a way that the uppermost paper sheet of the stack 1 of sheets is maintained at a predetermined height position with respect to the separator 4; a front plate 5 for controlling the position of the leading edge of the uppermost paper sheet; and a pair of feeding rollers 6 for feeding the uppermost paper sheet which has separated from the stack 1 of sheets in the manner described above. The separator 4 operates to separate only the uppermost sheet from the stack 1 of sheets and then feeds it in the direction indicated by the arrow A while the front plate 5 is retracted to the position indicated by the two-dot chain lines. The pair of feeding rollers 6 nips and feeds the uppermost paper sheet separated and fed in the manner described above while the main lift 3 is elevated to cause the second uppermost paper sheet of the stack of sheets to move to the above-mentioned predetermined height position with respect to the separator 4.
In the sheet feeding apparatus of the type described above, when the number of paper sheets 1 stacked on the pallet 2 reaches a predetermined number, the operator inserts a plurality of parallel spits 8 into respective parallel grooves formed in the upper surface of the pallet 2 in the direction of the feed of the sheets, and the spits 8 are maintained in their predetermined height positions by means of auxiliary lifts provided at the upstream and downstream sides of the sheet feeding apparatus. Under the above-described conditions, the main lift 3 is then lowered and the pallet 2 is removed. Thereafter, a new stack 1A of paper sheets is loaded on the main lift 3 as shown in FIG. 9. The stack 1 of paper sheets is now supported by the auxiliary lifts 9 through the spits 8 while the paper sheet feeding operation is carried out continuously by the separator. Supporting the new stack 1A of paper sheets, the main lift 3 is elevated until the uppermost paper sheet of the new stack 1A of sheets is brought into contact with the undersides of the spits 8. Thereafter, the spits 8 are withdrawn out of the feeding apparatus so that the old stack 1 of sheets is now placed on the new stack 1A of sheets thus loaded. Thus, the operation for loading a new stack of sheets is accomplished.
In the conventional paper sheet feeding apparatus described above, the operation of inserting and withdrawing the spits is carried out manually so that there arises a problem that at least one operator must engage solely in the sheet feeding operation.
Furthermore, as best shown in FIG. 10, the spits 8, which are inserted in the direction of the feed of the sheets so as to support the stack 1 of sheets, tend to deflect downwardly, so that the portion of the upper surface of the uppermost sheet 1 in opposing relationship with the separator 4 becomes lower than a reference position P at the midpoint between the ends of the leading edge of the uppermost sheet 1. As a result, in order to maintain the reference position P at a predetermined height, the adjustment of the position of the separator must be made. Moreover, during and after the piling of the old and new stacks 1 and 1A of sheets and the withdrawal of the spits, unless the amount of drop of the old stack 1 of sheets is made very small, the vacuum suction cups 4a and 4b and the air blowing pipe 4c of the separator 4 cannot take the correct height position relative to the uppermost sheet of the old stack 1 of sheets. As a result, there arise the problems that the sheets are fed with incorrect orientation into the printing press or punching machine and that in response to detection of incorrect sheet feeding by the printing press or punching machine, the operation of the latter is interrupted. Therefore, the operation of loading a new stack of sheets is greatly influenced by skillfulness and experience of the operator, and various incorrect feeding operations occur depending upon the difference in skill and experience among the operators. Consequently, the incorrect feeding operation is one of the factors which much adversely affects the productivity.
The above stated problems are solved by the present invention which will be described below.
FIG. 1 is a front sectional view of a preferred embodiment of the automatic sheet stack loading mechanism of a paper sheet feeding apparatus, according to the present invention. Reference numeral 11 represents a stack of paper sheets, which is supported by a drain-board-like pallet 12 having parallel grooves in the upper surface thereof. Reference numeral 13 represents a main lift upon which is mounted the stack 11 of paper sheets and the pallet 12. The main lift 13 is adapted to move upwardly or downwardly. Above the uppermost sheet of the stack 11 there is provided a sheet separator 14 for separating the uppermost paper sheet upwardly from the stack 11 of sheets to feed it to a predetermined position. The main lift 13 is coupled through main lift chains 15 (See FIG. 2) to an elevator mechanism (not shown), which causes the main lift 13 to move upwardly in such a way that as the uppermost sheet is separated from the stack 11 and is fed to a predetermined position, the next uppermost sheet of the stack 11 is brought to a predetermined height position with respect to the separator 14.
As best shown in FIG. 2, the main lift 13 has a bottom plate 18 which is supported by rollers 17 to be movable to the right or left as viewed, a motor 19 for moving the bottom plate 18 to the right or left, a pinion 20 on the driving shaft of the motor, and a rack 21 in mesh with the pinion 20. Therefore, the position of the stack 11 of paper sheets mounted on the plate 18 can be suitably adjusted with respect to the transverse direction as will be described in more detail hereinafter.
Referring back to FIG. 1, spit insertion mechanisms 23 (only one is shown in FIG. 1) are disposed at both sides of the stack 11 of sheets on the main lift 13. Each spit insertion mechanism 23 has a pedestal 24a erected upright on a floor, a stand 24b which is attached to a machine frame above the pedestal 24a, a vertical guide shaft 25 which is securely attached to the pedestal 24a and the stand 24b, a carriage 26 which is vertically movable along the guide shafts 25, and a balancer pneumatic cylinder 27 which supports the vertically movable carriage 26 in such a way that the carriage 26 may be lightly moved upwardly or downwardly, as well as the weight of various component parts mounted on the carriage 26.
As shown in FIG. 3, the vertically movable carriage 26 has a plurality of horizontal stack holding spits 29 each of which is supported by a slide bearing 28 (FIG. 1) for slidable movement in the horizontal direction. As shown in FIG. 1, there is provided a connecting member 30 to which are attached the proximal ends of the spits 29. There is further provided a sliding cylinder 31 for reciprocating the spits 29 through the connecting member 30 in the direction toward and away from the stack 11 of sheets. The sliding cylinder 31 constitutes a spit driving mechanism which reciprocates the sheet supporting spits 29 between their retracted positions spaced apart by a suitable distance from one side edge of the stack 11 of sheets and their advanced positions at which they support the load of the stack 11 of sheets from below.
FIGS. 2 and 4 show a plate-shaped sheet pressing device 34 which has sheet-detection limit switches 38 and 39 disposed at positions, respectively, above and below the spits 29 in such a way that their detecting members 38a and 39a project beyond the inner surface of the sheet pressing device 34. Pressing device 34 is moved by motive power means 36.
Referring to FIGS. 1 and 3, an auxiliary lift 41 is suspended in opposing relationship with each side face of the stack 11 of sheets, by means of chains 43 (See FIG. 3) passed within auxiliary hollow guides 42 (See FIG. 1). Each auxiliary lift 41 is disposed at a position at which it can abut against and support the undersurface 26a of an inward projection extending from the carriage 26 which supports the sheet supporting spits 29. The chains 43 are connected to a lifting motor mechanism (not shown), and, as best shown in FIG. 3, when the auxiliary lifts 41 support from below the stack 11 of sheets through the carriage 26 and the sheet supporting spits 29, the uppermost sheet of the stack 11 is successively brought to a position at a predetermined height with respect to the separator 14 due to successive incremental upward movement of the auxiliary lifts 41.
Referring to FIG. 1 again, a protrusion 45 is formed on the inner side surface of the carriage 26 in opposing and interfering relationship with the main lift 13 so that when the main lift 13 is upwardly moved to the position indicated in FIG. 1, the carriage 26 receives upward moving force through the protrusion 45. The position of the protrusion 45 is so selected that when the carriage 26 is supported through the protrusion 45 by the main lift 13, the sheet supporting spits 29 are in alignment with respective grooves of the pallet 12 for receiving the spits 29 into the grooves of the pallet.
FIG. 5 is a schematic perspective view illustrating the general arrangement of a device used to load a stack of sheets upon the main lift 13. The main lift 13 has roller conveyors 50 thereon. Reference numeral 51 indicates a traverser 51 with a roller conveyor; and 52, a stand upon which are place a plurality of stacks 11A of sheets. These stacks 11A of sheets are loaded one at a time from the stand 52 through the transverser 51 onto the main lift 13. The stack stand 52 is sequentially moved in the direction indicated by an arrow B as one stack is loaded on the main lift so that a plurality of stacks of sheets can be continuously loaded on the main lift one by one.
Next, referring to FIGS. 6A-6J, sequential steps of loading a stack of sheets by the mechanism with the above described construction will be explained.
In FIG. 6A, the main lift 13 upon which is supported the stack 11 of sheets 11 is upwardly moving, and the uppermost sheet of the stack 11 of paper sheets is separated one by one and fed to a predetermined position. In this condition, the stack supporting spits 29 are maintained in their retracted positions, at which they do not contact with the side faces of the stack 11. The auxiliary lifts 41 are also maintained at their inoperative positions.
Referring to FIG. 6B, when the main lift 13 is moved upwardly, it abuts against and raises the protrusions 45 as shown in FIG. 1 so that thereafter the carriages 26 are caused to move upwardly in unison with the upward movement of the main lift 13. When the main lift 13 reaches a predetermined height, a sensor (not shown) detects the main lift 13 raised to the predetermined height and energizes the sliding cylinders 31 so that the spits 29 are shifted in the transverse directions indicated by the arrows C to the both sides of the stack 11 of sheets and slidingly inserted into the grooves in the upper surface of the pallet 12 immediately below the lowermost sheet of the stack 11.
Thereafter, as shown in FIG. 6C, the auxiliary lifts 41 are moved upwardly to support the spits 29 through the carriages 26 (See also FIG. 3) so that the stack 11 of sheets are supported through the sheet supporting spits 29 by the auxiliary lifts 41. After that, the upward movement of the auxiliary lifts 41 is so controlled that the uppermost sheet of the stack 11 is brought to a predetermined height position with respect to the sheet separator 14. It therefore follows that the auxiliary lifts 41 are moved upwardly depending upon the number of sheets which have been separated from the stack 11 and fed to a predetermined position.
When the spits 29 support the stack 11 of sheets, they tend to deflect downwardly depending upon the weight of the stack. According to the present invention, the spits 29 are inserted from both sides of the stack 11 with respect to the direction transverse to the direction of feed of the sheets so that even when the spits are deflected downwardly with the result that the center portion of each sheet of the stack 11 becomes downwardly concave, the height of the center portion of each sheet is maintained at a predetermined height in the direction of feed of the sheet. As a result, unlike the conventional mechanism for loading a stack of sheets described before with reference to FIG. 10, it is not necessary to adjust the height of the sheet separator 14.
As shown in FIG. 6D, while the stack 11 of sheets is supported by the spits 29 which in turn are supported by the auxiliary lifts 41 and while each sheet of the stack 11 is separated and fed to a predetermined position, the main lift 13 with the empty pallet 12 thereon is moved downwardly.
As shown in FIGS. 6E and 6F, the main lift 13 is moved down to the lower end of its stroke, and the pallet 12 is removed in the direction indicated by an arrow D by a suitable device or manually.
Next, as shown in FIGS. 6G and 5, a new stack 11A of sheets is loaded on the main lift 13 by the traverser 51. It must be pointed out here that the side faces of the old and newly loaded stacks 11 and 11A are not necessarily aligned with each other.
Thereafter, as shown in FIG. 6H, the main lift 13 is moved upwardly until the uppermost sheet of the newly loaded stack 11A is slightly below the spits 29. Next, the sheet pressing devices 34 on both sides are advanced to abut against the side faces of the old and newly loaded stacks 11 and 11A, and the transverse positions of the new stack 11A are adjusted. Such adjustment is done in the following manner. That is, as shown in FIG. 2, the sheet pressing devices 34 are advanced in the directions indicated by an arrow E. Then, the detecting member 39a of the lower limit switch 39 is brought into contact with the side faces of the newly loaded stack 11A and the lower limit switch 39 generates a detection signal. In response to this signal, the motor 19 is energized so that the bottom plate 18 is displaced in the direction indicated by the arrow E. In unison with this displacement, the sheet pressing devices 34 are also displaced in the same direction E. When the position of the old stack 11 coincides with the position of the newly loaded stack 11A, the detecting member 38a of the upper limit switch 38 is brought into contacts with the side faces of the old stack 11 so that the upper limit switch 38 generates a detection signal. In response to the reception of both the detection signals, the motor 19 is de-energized. Thus, the transverse side faces of the newly loaded stack 11A are adjusted. In case the newly loaded stack 11A is deviated to the right as viewed in FIG. 2 with respect to the old stack 11, it is the upper limit switch 38 that first generates a detection signal. In this case, the motor 19 is energized to displace the bottom plate 18 in the direction opposite to the direction indicated by the arrow E. When both the upper and lower limits switches 38 and 39 are actuated, the motor 19 is de-energized, whereby the position of the newly loaded stack 11A is determined.
Thereafter, as shown in FIG. 6I, the main lift 13 is moved upwardly and the lowermost sheet of the old stack 11 is caused to rest through the spits 29 upon the uppermost sheet of the newly loaded stack 11A. Then, the upward movement of the main lift 13 is so adjusted that the uppermost sheet is brought to a predetermined position with respect to the separator 14. The auxiliary lifts 41 are moved then downwardly to their initial positions.
As shown in FIG. 6J, the sheet supporting spits 29 are thereafter withdrawn or retracted slowly in the right and left directions, respectively, so that the old stack 11 is mounted on the uppermost sheet of the newly loaded stack 11A. In this case, the sheet pressing devices 34 press both side faces of the stacks 11 and 11A so that there occurs no disorder of these stacks.
As shown in FIG. 7, when the left and right spits 29 are withdrawn to the left and right respectively, the central portion 11a of the sheet stack 11 immediately below the separator 14 drops slowly since the both side portion of the stack 11 supported by the spits 29 are released gradually from the support by the spits 29. When the speed of withdrawal of the spits 29 is suitably selected, the central portion 11a of the uppermost sheet will not be suddenly separated from the separator 14. As a result, the failure of right feed (the failure of feeding sheets one by one) can be avoided.
After the spits 29 are withdrawn to the right and left, the sheet pressing devices 34 are returned to their initial positions, respectively, and the pneumatic cylinder 27 is energized so that the carriage 26 upon which are mounted the spits 29 and the sheet pressing devices 34 is moved downwardly to its initial position. Thus, the loading of a new stack 11A of sheet is accomplished.
According to the preferred embodiment of the present invention, the auxiliary lifts 41 which support the spits 29 through the carriages 26 is caused to move upwardly, but it is to be understood that the auxiliary lifts 41 may be so designed and constructed that they directly support the sheet supporting spits 29. Furthermore, so far the sheet supporting spits 29 have been described as being horizontally slidable with respect to the carriage 26, but it is also to be understood that the spits 29 may be securely attached to the carriage 26 and the vertical guide shaft 25 supporting the carriage 26 may be horizontally displaced so that the spits 29 may be reciprocated in the horizontal direction.
Moreover, according to the preferred embodiment, as shown in FIG. 5, in order to load a new stack 11A of sheets, the roller conveyors 50 are mounted on the main lift 13 and the traverser 51 and the stack stand 52 for placing thereon a plurality of stacks of sheets are disposed on the upstream side of the main lift 13, but it is to be understood that any other suitable mechanism may be used or a manually operated hand-lift or the like may be used.
As described above, according to the automatic sheet stack loading mechanism of the present invention, the sheet supporting spits are inserted from both sides of the path of feed of sheets so that even when the spits are deflected, the adjustment of the position of the sheet separator is not needed. When the sheet supporting spits are withdrawn from the interface between the lowermost sheet of the old stack of sheets and the uppermost sheet of the newly loaded stack of sheets, sudden drop of the central portion of the uppermost sheet in opposing relationship with the separator can be prevented so that sudden increase in gap between the separator and the uppermost sheet can be prevented and consequently the sheet feeding failure is avoided. The sheet pressing devices which may be additionally installed are effective in that when the spits are withdrawn, the mis-alignment of the side faces of the sheet stacks can be avoided. According to the present invention, it becomes possible to automate the operation of loading a new stack of sheets on the main lift, which operation was hitherto carried out only by a skilled operator, so that a new stack of sheets can be always loaded on the main lift without causing the sheet feed failure. Thus, the present invention can attain the effects of saving labors and improving productivity. | An automatic sheet stack loading mechanism of a paper sheet feeding apparatus has a main lift for supporting a stack of sheets to be fed thereon. The main lift is incrementally moved upwardly to place the uppermost sheet of the stack at a predetermined height position with respect to a sheet separator disposed over the stack and operating to separate the sheets one by one from the stack. When the stack of sheets is consumed considerably, parallel horizontal spits are inserted under the stack from both transverse sides of the stack thereby to support the load of the stack and to enable the main lift to be lowered to receive a new stack of the sheets. The insertion of the spits in the transverse direction of the stack is advantageous in that the central portion of the sheets of the stack along the direction of feed of the sheets is maintained at constant height irrespective of downward deflection of the spits so that adjustment in position of the sheet separator is not required. | 1 |
[0001] The present invention relates to derivatives of the ecteinascidins, particularly ecteinascidin 736 (ET-736), pharmaceutical compositions containing them and their use as antitumoral compounds.
BACKGROUND OF THE INVENTION
[0002] The ecteinascidins are exceedingly potent antitumour agents isolated from the marine tunicate Ecteinascidia turbinata. Several ecteinascidins have been reported previously in the patent and scientific literature. See, for example:
[0003] U.S. Pat. No. 5,256,663, which describes pharmaceutical compositions comprising matter extracted from the tropical marine invertebrate, Ecteinascidia turbinata, and designated therein as ecteinascidins, and the use of such compositions as antibacterial, anti-viral, and/or antitumour agents in mammals.
[0004] U.S. Pat. No. 5,089,273, which describes novel compositions of matter extracted from the tropical marine invertebrate, Ecteinascidia turbinata, and designated therein as ecteinascidins 729, 743, 745, 759A, 759B and 770. These compounds are useful as antibacterial and/or antitumour agents in mammals.
[0005] U.S. Pat. No. 5,149,804 which describes Ecteinascidins 722 and 736 (Et's 722 and 736) isolated from the Caribbean tunicate Ecteinascidia turbinata and their structures. Et's 722 and 736 protect mice in vivo at very low concentrations against P388 lymphoma, B16 melanoma, and Lewis lung carcinoma.
[0006] U.S. Pat. No. 5,478,932, which describes ecteinascidins isolated from the Caribbean tunicate Ecteinascidia turbinata, which provide in vivo protection against P388 lymphoma, B16 melanoma, M5076 ovarian sarcoma, Lewis lung carcinoma, and the LX-1 human lung and MX-1 human mammary carcinoma xenografts.
[0007] U.S. Pat. No. 5,654,426, which describes several ecteinascidins isolated from the Caribbean tunicate Ecteinascidia turbinata, which provide in vivo protection against P388 lymphoma, B16 melanoma, M5076 ovarian sarcoma, Lewis lung carcinoma, and the LX-1 human lung and MX-1 human mammary carcinoma xenografts.
[0008] U.S. Pat. No. 5,721,362 which describes a synthetic process for the formation of ecteinascidin compounds and related structures.
[0009] U.S. Pat. No. 6,124,292 which describes a series of new ecteinascidin-like compounds.
[0010] WO 0177115, WO 0187894 and WO 0187895, which describe new synthetic compounds of the ecteinascidin series, their synthesis and biological properties.
[0011] See also: Corey, E. J., J. Am. Chem. Soc., 1996, 118 pp. 9202-9203; Rinehart, et al., Journal of Natural Products, 1990, “Bioactive Compounds from Aquatic and Terrestrial Sources”, vol. 53, pp. 771-792; Rinehart et al., Pure and Appl. Chem., 1990, “Biologically active natural products”, vol 62, pp. 1277-1280; Rinehart, et al., J. Org. Chem., 1990, “Ecteinascidins 729, 743, 745, 759A, 759B, and 770: potent Antitumour Agents from the Caribbean Tunicate Ecteinascidia turninata ”, vol. 55, pp. 4512-4515; Wright et al., J. Org. Chem., 1990, “Antitumour Tetrahydroisoquinoline Alkaloids from the Colonial ascidian Ecteinascidia turbinata ”, vol. 55, pp. 4508-4512; Sakai et al., Proc. Natl. Acad. Sci. USA 1992, “Additional anitumor ecteinascidins from a Caribbean tunicate: Crystal structures and activities in vivo”, vol. 89, 11456-11460; Science 1994, “Chemical Prospectors Scour the Seas for Promising Drugs”, vol. 266, pp. 1324; Koenig, K. E., “Asymmetric Synthesis”, ed. Morrison, Academic Press, Inc., Orlando, Fla., vol. 5, 1985, p. 71; Barton, et al., J. Chem Soc. Perkin Trans., 1, 1982, “Synthesis and Properties of a Series of Sterically Hindered Guanidine bases”, pp. 2085; Fukuyama et al., J. Am. Chem. Soc., 1982, “Stereocontrolled Total Synthesis of (+)-Saframycin B”, vol. 104, pp. 4957; Fukuyama et al., J. Am. Chem. Soc., 1990, “Total Synthesis of (+)—Saframycin A”, vol. 112, p. 3712; Saito, et al., J. Org. Chem., 1989, “Synthesis of Saframycins. Preparation of a Key tricyclic Lactam Intermediate to Saframycin A”, vol. 54, 5391; Still, et al., J. Org. Chem., 1978, “Rapid Chromatographic Technique for Preparative Separations with Moderate Resolution”, vol. 43, p. 2923; Kofron, W. G.; Baclawski, L. M., J. Org. Chem., 1976, vol. 41, 1879; Guan et al., J. Biomolec. Struc. & Dynam., vol. 10, pp. 793-817 (1993); Shamma et al., “Carbon-13 NMR Shift Assignments of Amines and Alkaloids”, p. 206 (1979); Lown et al., Biochemistry, 21, 419-428 (1982); Zmijewski et al., Chem. Biol. Interactions, 52, 361-375 (1985); Ito, CRC Crit. Rev. Anal. Chem., 17, 65-143 (1986); Rinehart et al., “Topics in Pharmaceutical Sciences 1989”, pp. 613-626, D. D. Breimer, D. J. A. Cromwelin, K. K. Midha, Eds., Amsterdam Medical Press B. V., Noordwijk, The Netherlands (1989); Rinehart et al., “Biological Mass Spectrometry”, 233-258 eds. Burlingame et al., Elsevier Amsterdam (1990); Guan et al., Jour. Biomolec. Struct. & Dynam., vol. 10 pp. 793-817, (1993); Nakagawa et al., J. Amer. Chem. Soc., 111: 2721-2722 (1989); Lichter et al., “Food and Drugs from the Sea Proceedings” (1972), Marine Technology Society, Washington, D.C. 1973, 117-127; Sakai et al., J. Amer. Chem. Soc., 1996, 118, 9017; Garcia-Rocha et al., Brit. J. Cancer, 1996, 73: 875-883; and pommier et al., Biochemistry, 1996, 35: 13303-13309;
[0012] In 2000, a hemisynthetic process for the formation of ecteinascidin compounds and related structures such as phthalascidin starting from natural bis(tetrahydroisoquinoline) alkaloids such as the saframycin and safracin antibiotics available from different culture broths was reported; See Manzanares et al., Org. Lett., 2000, “Synthesis of Ecteinascidin ET-743 and Phthalascidin Pt-650 from Cyanosafracin B”, Vol. 2, No 16, pp. 2545-2548; and International Patent Application WO 00 69862.
[0013] Ecteinascidin 736 was first discovered by Rinehart and features a tetrahydro-β-carboline unit in place of the tetrahydroisoquinoline unit more usually found in the ecteinascidin compounds isolated from natural sources; See for example Sakai et al., Proc. Natl. Acad. Sci. USA 1992, “Additional antitumor ecteinascidins from a Caribbean tunicate: Crystal structures and activities in vivo”, vol. 89, 11456-11460.
[0014] WO 9209607 claims ecteinascidin 736, as well as ecteinascidin 722 with hydrogen in place of methyl on the nitrogen common to rings C and D of ecteinascidin 736 and O-methylecteinascidin 736 with methoxy in place of hydroxy on ring C of ecteinascidin 736.
[0015] Despite the positive results obtained in clinical applications in chemotherapy, the search in the field of ecteinascidin compounds is still open to the identification of new compounds with optimal features of cytotoxicity and selectivity toward the tumour and with a reduced systemic toxicity and improved pharmacokinetic properties.
SUMMARY OF THE INVENTION
[0016] The present invention is directed to compounds of the general formula I:
wherein the substituent groups for R 1 , R 2 , R 3 , R 4 , and R 5 are each independently selected from the group consisting of H, OH, OR′, SH, SR′, SOR′, SO 2 R′, C(═O)R′, C(═O)OR′, NO 2 , NH 2 , NHR′, N(R′) 2 , NHC(O)R′, CN, halogen, ═O, substituted or unsubstituted C 1 -C 18 alkyl, substituted or unsubstituted C 2 -C 18 alkenyl, substituted or unsubstituted C 2 -C 18 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclic; wherein X is independently selected of OR′, CN, (═O), or H. wherein each of the R′ groups is independently selected from the group consisting of H, OH, NO 2 , NH 2 , SH, CN, halogen, ═O, C(═O)H, C(═O)CH 3 , CO 2 H, substituted or unsubstituted C 1 -C 18 alkyl, substituted or unsubstituted C 2 -C 18 alkenyl, substituted or unsubstituted C 2 -C 18 alkynyl, substituted or unsubstituted aryl; wherein m is 0, 1 or 2; and wherein n is 0, 1, 2, 3 or 4.
[0022] The present invention also relates to the synthesis of ecteinascidin 736 (where R 1 , R 3 , R 4 , R 5 =H, R 2 =CH3CO— and X=OH) and related compounds of the general formula I or Ia.
[0023] In another aspect, the invention relates to pharmaceutical compositions comprising a compound of formula I.
[0024] In another aspect, the invention relates to the use of compounds of general formula I or Ia in the treatment of cancer.
[0025] As one group, the invention provides compounds of formula I or Ia, wherein:
R 1 is hydrogen, hydroxy, halogen, alkoxy or aralkyl; R 2 and R 3 are independently selected from hydrogen, R′, C═OR′, or COOR′, where R′ is optionally substituted alkyl or alkenyl, the optional substituents being chosen from halo, amino including amino derived from amino acid, aryl or heterocyclic; R 4 is hydrogen, alkyl or C(═O)OR′, where R′ is alkylene. R 5 is hydrogen or alkyl; X is hydrogen, hydroxy, cyano or keto; m is 0 or 1; and n is 0 or 1.
[0033] Suitable halogen substituents in the compounds of the present invention include F, Cl, Br and I.
[0034] Alkyl groups preferably have from 1 to 24 carbon atoms. One more preferred class of alkyl groups has 1 to about 12 carbon atoms, yet more preferably 1 to about 8 carbon atoms, still more preferably 1 to about 6 carbon atoms, and most preferably 1, 2, 3 or 4 carbon atoms. Another more preferred class of alkyl groups has 12 to about 24 carbon atoms, yet more preferably 12 to about 18 carbon atoms, and most preferably 13, 15 or 17 carbon atoms. Methyl, ethyl and propyl including isopropyl are particularly preferred alkyl groups in the compounds of the present invention. As used herein, the term alkyl, unless otherwise modified, refers to both cyclic and noncyclic groups, although cyclic groups will comprise at least three carbon ring members.
[0035] Preferred alkenyl and alkynyl groups in the compounds of the present invention have one or more unsaturated linkages and from 2 to about 12 carbon atoms, more preferably 2 to about 8 carbon atoms, still more preferably 2 to about 6 carbon atoms, even more preferably 1, 2, 3 or 4 carbon atoms. The terms alkenyl and alkynyl as used herein refer to both cyclic and noncyclic groups, although straight or branched noncyclic groups are generally more preferred.
[0036] Preferred alkoxy groups in the compounds of the present invention include groups having one or more oxygen linkages and from 1 to about 12 carbon atoms, more preferably from 1 to about 8 carbon atoms, and still more preferably 1 to about 6 carbon atoms, and most preferably 1, 2, 3 or 4 carbon atoms.
[0037] Preferred alkylthio groups in the. compounds of the present invention have one or more thioether linkages and from 1 to about 12 carbon atoms, more preferably from 1 to about 8 carbon atoms, and still more preferably 1 to about 6 carbon atoms. Alkylthio groups having 1, 2, 3 or 4 carbon atoms are particularly preferred.
[0038] Preferred alkylsulphinyl groups in the compounds of the present invention include those groups having one or more sulphoxide (SO) groups and from 1 to about 12 carbon atoms, more preferably from 1 to about 8 carbon atoms, and still more preferebly 1 to about 6 carbon atoms. Alkylsulphinyl groups having 1, 2, 3 or 4 carbon atoms are particularly preferred.
[0039] Preferred alkylsulphonyl groups in the compounds of the present invention include those groups having one or more sulphonyl (SO 2 ) groups and from 1 to about 12 carbon atoms, more preferably from 1 to about 8 carbon atoms, and still more preferably 1 to about 6 carbon atoms. Alkylsulphonyl groups having 1, 2, 3 or 4 carbon atoms are particularly preferred.
[0040] Preferred aminoalkyl groups include those groups having one or more primary, secondary and/or tertiary amine groups, and from 1 to about 12 carbon atoms, more preferably 1 to about 8 carbon atoms, still more preferably 1 to about 6 carbon atoms, even more preferably 1, 2, 3 or 4 carbon atoms. Secondary and tertiary amine groups are generally more preferred than primary amine moieties.
[0041] Suitable heterocyclic groups include heteroaromatic and heteroalicyclic groups. Suitable heteroaromatic groups in the compounds of the present invention contain one, two or three heteroatoms selected from N, O or S atoms and include, e.g., coumarinyl including 8-coumarinyl, quinolinyl including 8-quinolinyl, pyridyl, pyrazinyl, pyrimidyl, furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, indolyl, benzofuranyl and benzothiazol. Suitable heteroalicyclic groups in the compounds of the present invention contain one, two or three heteroatoms selected from N, O or S atoms and include, e.g., tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholino and pyrrolindinyl groups.
[0042] Suitable carbocyclic aryl groups in the compounds of the present invention include single and multiple ring compounds, including multiple ring compounds that contain separate and/or fused aryl groups. Typical carbocyclic aryl groups contain 1 to 3 separate or fused rings and from 6 to about 18 carbon ring atoms. Specifically preferred carbocyclic aryl groups include phenyl including substituted phenyl such as 2-substituted phenyl, 3-substituted phenyl, 2.3-substituted phenyl, 2.5-substituted phenyl, 2.3.5-substituted and 2.4.5-substituted phenyl, including where one or more of the phenyl substituents is an electron-withdrawing group such as halogen, cyano, nitro, alkanoyl, sulphinyl, sulphonyl and the like; naphthyl including 1-naphthyl and 2-naphthyl; biphenyl; phenanthryl; and anthracyl.
[0043] References herein to substituted R′ groups in the compounds of the present invention refer to the specified moiety, typically alkyl or alkenyl, that may be substituted at one or more available positions by one or more suitable groups, e.g., halogen such as fluoro, chloro, bromo and iodo; cyano; hydroxyl; nitro; azido; alkanoyl such as a C1-6 alkanoyl group such as acyl and the like; carboxamido; alkyl groups including those groups having 1 to about 12 carbon atoms or from 1 to about 6 carbon atoms and more preferably 1-3 carbon atoms; alkenyl and alkynyl groups including groups having one or more unsaturated linkages and from 2 to about 12 carbon or from 2 to about 6 carbon atoms; alkoxy groups having those having one or more oxygen linkages and from 1 to about 12 carbon atoms or 1 to about 6 carbon atoms; aryloxy such as phenoxy; alkylthio groups including those moieties having one or more thioether linkages and from 1 to about 12 carbon atoms or from 1 to about 6 carbon atoms; alkylsulphinyl groups including those moieties having one or more sulphinyl linkages and from 1 to about 12 carbon atoms or from 1 to about 6 carbon atoms; alkylsulphonyl groups including those moieties having one or more sulphonyl linkages and from 1 to about 12 carbon atoms or from 1 to about 6 carbon atoms; aminoalkyl groups such as groups having one or more N atoms and from 1 to about 12 carbon atoms or from 1 to about 6 carbon atoms; carbocylic aryl having 6 or more carbons, particularly phenyl (e.g., R being a substituted or unsubstituted biphenyl moiety); and aralkyl such as benzyl; heterocyclic groups including heteroalicyclic and heteroaromatic groups, especially with 5 to 10 ring atoms of which 1 to 4 are heteroatoms, more preferably heterocyclic groups with 5 or 6 ring atoms and 1 or 2 heteratoms or with 10 ring atoms and 1 to 3 heteroatoms.
[0044] Preferred R′ groups are present in groups of formula R′, COR′ or OCOR′ and include alkyl or alkenyl, that may be substituted at one or more available positions by one or more suitable groups, e.g., halogen such as fluoro, chloro, bromo and iodo, especially (o-chloro or perfluoro; aminoalkyl groups such as groups having one or more N atoms and from 1 to about 12 carbon atoms or from 1 to about 6 carbon atoms, and especially including amino acid, notably glycine, alanine, arginine, asparagine, asparaginic acid, cystein, glutamine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine or valine, especially protected forms of such amino acids; carbocylic aryl having 6 or more carbons, particularly phenyl; and aralkyl such as benzyl; heterocyclic groups including heteroalicyclic and heteroaromatic groups, especially with 5 to 10 ring atoms of which 1 to 4 are heteroatoms, more preferably heterocyclic groups with 5 or 6 ring atoms and 1 or 2 heteratoms or with 10 ring atoms and 1 to 3 heteroatoms, the heterocyclic groups optionally being substituted with one or more of the subsitituents permitted for R′ and especially amino such as dimethylamino or with keto.
[0045] Without being exhaustive, preferred compounds of this invention have one or more of the following definitions:
[0046] R 1 is H; hydroxy; halogen, especially F, alkyoxy (alkyl being 1 to 7 carbon atoms), especially C 1 to C 3 alkyl and benzyloxy, most especially methoxy and benzyloxy. Particularly preferred are H, OH or OMe.
[0047] R 2 is H; or acetyl; alkyl-CO (alkyl being up to 25 carbon atoms, such as up to 17, 19 or 21 carbon atoms and preferably an odd number of carbon atoms corresponding to a fatty acid carboxylic acid of even number of carbon atoms or else a low number of carbon atoms such as 1 to 7) especially CH 3 —(CH 2 ) n —CO— where n is for example 1, 2, 4, 6, 12, 14 or 16; haloalkyl-CO—, especially trifluoromethylcarbonyl, heptafluorobutyrylcarbonyl or 3-chloropropionyl; arylalkyl-CO—; arylalkenyl-CO—, especially cinnamoyl-CO—; alkyl-O—CO—, especially t-butyl-O—CO— or alkenyl-O—CO—, especially allyl-O—CO— or vinyl-O—CO.
[0048] R 3 is preferably H; alkenyl, especially allyl; alkyl-CO_ (alkyl being up to 25 carbon atoms, such as up to 17, 19 or 21 carbon atoms and preferably an odd number of carbon atoms corresponding to a fatty acid carboxylic acid of even number of carbon atoms or else a low number of carbon atoms such as 1 to 6) especially CH 3 —(CH 2 ) n —CO— where n is for example 1, 2, 4, 6, 12, 14 or 16; alkyl-O—CO—, especially t-butyl-O—CO—; alkenyl-O—CO, especially allyl-O—CO-and vinyl-O—CO.
[0049] R 4 is preferably H, alkyl (alkyl being 1 to 6 carbon atoms) especially C 1 to C 3 alkyl; alkenyl especially allyl, alkenyl-O—CO— especially vinyl-O—CO and R 4 is most especially H.
[0050] R 5 is H or alkyl (alkyl being 1 to 6 carbon atoms) and R 5 is most especially H or Me.
[0051] X is a H, —CN or OH, most especially —OH or —CN.
[0052] m is 0 or 1.
[0053] n is 0 or 1.
[0054] Compounds where R1 is not hydrogen are one class of preferred compounds. See for example compounds 27 to 36. These compounds have higher activity, a wider therapeutic window and improved pharmacokinetic properties. Preferred substituents are methoxy, methyl, hydroxy, benzyloxy, fluoro.
[0055] Compounds wherein R 3 is an ester or an ether are among the preferred compounds. In general they have improved toxicology properties and thus give a wider therapeutic window. Of those, compounds with an ester or carbonate at this position are most preferred, and in particular carbonates. Esters with bulky groups (long aliphatic or aromatic residues) give better results. Among the carbonates, terButyloxycarbonyl (TBOC) and vinyloxycarbonyl (VOC) are the most preferred substituents for these positions.
[0056] Compounds where R 5 is not hydrogen are another class of preferred compounds. See for example compounds 37 to 44. These compounds tend to be less active (cytotoxic) but have lower toxicity and improved pharmacokinetic properties. When R 5 is not hydrogen a chiral center is generated, and we have found that there is difference in activity between the diastereoisomers.
[0057] Compounds wherein R 2 is an ester or an ether are also preferred compounds. In general they have improved toxicology properties and thus give a wider therapeutic window. Of those, compounds with an ester or carbonate at this position are most preferred, and in particular carbonates. Esters with bulky groups (long aliphatic or aromatic residues) give better results. Among the carbonates, terButyloxycarbonyl (TBOC) and vinyloxycarbonyl (VOC) are the most preferred substituents for these positions.
[0058] There are compounds that have good ADME properties (absorption-distribution-metabolism-excretion) which are good indicative of pharmacokinetics.
[0059] As mentioned above, compounds of the present invention, preferably those with bulky substituted groups, have a good therapeutic window and the estherification of the phenols with different acids and carbonates, results in a general enhancement of the pharmaceutical properties: there is a significant decrease in hepatocyte toxicity, and also a good profile on drug-drug interactions since these derivatives do not show cytochrome inhibition having moreover higher metabolic stability.
[0060] Several active antitumor compounds have been prepared and it is believed that many more compounds may be formed in accordance with the teachings of the present disclosure.
[0061] Antitumoural activities of these compounds include leukaemias, lung cancer, colon cancer, kidney cancer, prostate cancer, ovarian cancer, breast cancer, sarcomas and melanomas.
[0062] Another especially preferred embodiment of the present invention is pharmaceutical compositions useful as antitumour agents which contain as active ingredient a compound or compounds of the invention, as well as the processes for their preparation.
[0063] Examples of pharmaceutical compositions include any solid (tablets, pills, capsules, granules etc) or liquid (solutions, suspensions or emulsions) with suitable compositions or oral, topical or parenteral administration.
[0064] Administration of the compounds or compositions of the present invention may be any suitable method, such as intravenous infusion, oral preparation, intraperitoneal and intravenous preparation.
[0065] The compounds and compositions of this invention may be used with other drugs to provide a combination therapy. The other drugs may form part of the same composition, or be provided as a separate composition for administration at the same time or a different time. The identity of the other drug is not particularly limited, and suitable candidates include:
a) drugs with antimitotic effects, especially those which target cytoskeletal elements, including microtubule modulators such as taxane drugs (such as taxol, paclitaxel, taxotere, docetaxel), podophylotoxins or vinca alkaloids (vincristine, vinblastine); b) antimetabolite drugs such as 5-fluorouracil, cytarabine, gemcitabine, purine analogues such as pentostatin, methotrexate); c) alkylating agents such as nitrogen mustards (such as cyclophosphamide or ifosphamide); d) drugs which target DNA such as the antracycline drugs adriamycin, doxorubicin, pharmorubicin or epirubicin; e) drugs which target topoisomerases such as etoposide; f) hormones and hormone agonists or antagonists such as estrogens, antiestrogens (tamoxifen and related compounds) and androgens, flutamide, leuprorelin, goserelin, cyprotrone or octreotide; g) drugs which target signal transduction in tumour cells including antibody derivatives such as herceptin; h) alkylating drugs such as platinum drugs (cis-platin, carbonplatin, oxaliplatin, paraplatin) or nitrosoureas; i) drugs potentially affecting metastasis of tumours such as matrix metalloproteinase inhibitors; j) gene therapy and antisense agents; k) antibody therapeutics; l) other bioactive compounds of marine origin, notably the didemnins such as aplidine; m) steroid analogues, in particular dexamethasone; n) anti-inflammatory drugs, in particular dexamethasone; and o) anti-emetic drugs, in particular dexamethasone.
[0081] Yet another especially preferred embodiment of the present invention is the synthetic intermediates of the compounds of the present invention as described in detail below.
[0082] Finally, the present invention includes the synthetic processes described herein.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0083] One class of preferred compounds of this invention includes compounds of this invention which have one or more of the following substituents: R 1 is hydrogen, hydroxy, halogen especially flouro, alkoxy especially methoxy, or aralkyl especially benzyl;
[0084] R 2 is hydrogen;
[0085] alkyl, more preferably alkyl of 1 to 6 carbon atoms;
[0086] C(═O)R′, where R′ is alkyl, more preferably alkyl of 1 to 24 carbon atoms, especially 1 to 8 or 12 to 18 carbon atoms; haloalkyl, more preferably ω-chloro- or perfluoro-alkyl of 1 to 4 carbon atoms, especially ω-chloroethyl or perfluoromethyl, ethyl or propyl; heterocylicalkyl, more preferably an aylkyl of 1 to 6 carbon atoms with an ω-heterocyclic substituent suitably having 5 to 10 ring atoms and 1 to 4 heteroatoms, including fused heteroalicyclic with 3 hetero atoms, such as biotin; aminoalkyl, more preferably alkyl of 1 to 6 carbon atoms, especially 2 carbon atoms, with an ω-amino group optionally protected for example with alkoxycarbonyl such as (CH 3 ) 3 C—O—C═O— or other protecting group;
[0087] arylalkylene, especially cinnamoyl; alkylene, especially vinyl or allyl; aralkyl, such as benzyl; or
[0088] C(═O)OR′, where R′ is alkyl, more preferably alkyl of 1 to 6 carbon atoms, especially branched alkyl; alkenyl, more preferably allyl;
[0089] R 3 is hydrogen;
[0090] alkyl, more preferably alkyl of 1 to 6 carbon atoms;
[0091] (C═O)R′, where R′ is alkoxy, especially with an alkyl group of 1 to 6 carbon atoms; alkyl, more preferably alkyl of 1 to 24 carbon atoms, preferably 1 to 8 or 12 to 18 carbon atoms; haloalkyl, more preferably perfluoroalkyl of 1 to 4 carbon atoms, especially perfluoromethyl, ethyl or propyl; arylalkylene, especially cinnamoyl; heterocylicalkyl, more preferably an alkyl of 1 to 6 carbon atoms with an ω heterocyclic substituent suitably having 5 to 12 ring atoms and 1 to 4 heteroatoms, including fused heterocyclic with 3 ring atoms, such as biotin; heterocyclicalkyl, with preferably 1 carbon atom in the alkyl group, and more preferably heteroalicylicmethyl with 5 to 10 ring atoms and 1 to 4 ring atoms, especially fused heterocylic with 1 to 4 heteroatoms, such as dimethylaminocoumarin or coumarin; alkylene, especially allyl; aralkyl, such as benzyl;
[0092] (C═O)OR′, where R′ is alkyl, more preferably alkyl of 1 to 6 carbon atoms; alkylene, especially vinyl or allyl; aralkyl, such as benzyl.
[0093] R 4 is hydrogen;
[0094] alkyl, more preferably alkyl of 1 to 6 carbon atoms;
[0095] (C═O)OR′, where R′ is alkylene, especially vinyl.
[0096] R 5 is hydrogen or alkyl.
[0097] X is hydrogen, hydroxy, cyano or keto.
[0098] m is 0 or 1.
[0099] n is 0 or 1.
[0100] In a related aspect of this invention, the compounds have one or more of the following features:
[0101] R 2 is not acetyl. Preferably it has at least 4, 5 or 6 carbon atoms, for example up to 18 or 24 carbon atoms. Suitable substituents include esters COR′, where R′ is alkyl, alkenyl, often with one or more substituents. Alkyl, substituted alkyl, alkenyl and arylalkenyl are preferred, with suitable substituents including aryl, heterocyclic. Other defintions for R 2 include esters of formula COR′ derived from an amino acid, optionally a protected amino acid.
[0102] R 3 is not hydrogen. Preferably it is R′, COR′ or COOR′ where R′ is a substituent with some bulk. Such bulky substituents include those with branched chain groups, unsaturated groups or cyclic groups including aromatic groups. Thus, branched alkyl, cycloalkyl, branched alkenyl, aryl, heteroaromatic and related groups are preferred for inclusion within the structure of the substituent R 3 . Preferably the total number of carbon atoms in R 3 is 2 to 24, more preferably 6 to 18 carbon atoms. Typically R 3 is an ester, ether or carbonate, being of formula COR′, R′ or COOR′.
[0103] R 5 is not hydrogen. Preferably it is R′, COR′ or COOR′ where R′ is a substituent with some bulk. Such bulky substituents include those with branched chain groups, unsaturated groups or cyclic groups including aromatic groups. Thus, branched alkyl, cycloalkyl, branched alkenyl, aryl, heteroaromatic and related groups are preferred for inclusion within the structure of the substituent R 5 . Preferably the total number of carbon atoms in R 5 is 2 to 24, more preferably 6 to 18 carbon atoms. Typically R 4 is an ester, ether or carbonate, being of formula COR′, R′ or COOR′.
[0104] Examples of protecting groups for amino and other substituents are given in WO 0069862, and we expressly incorporate that disclosure.
[0105] This application claims priority of a British patent application. We expressly incorporate by reference any disclosure which is in the specification of that British priority application and which is not in the present application.
[0106] Furthermore, we expressly incorporate by reference each of WO 0069862, WO 0177115, WO 0187894 and WO 0187895 for their discussion of substituents which correspond to the substituents of the present invention. Any definitions given in any of these earlier applications for a particular substituent can be adopted for a substituent of a compound of this invention.
[0107] Furthermore, we do not claim any of the compounds disclosed in the earlier applications, including WO 9209607, and we expressly disclaim any such compounds. We expressly incorporate by reference each of the earlier applications for the wording of any disclaimer which might be necessary.
[0108] Disclosed in international patent application WO 0069862 is compound 36 (an intermediate in the conversion of cyanosafracin B to Ecteinascidin 743).
[0109] This hemi-synthetic intermediate has served as the starting material for the synthesis of ecteinascidin 736, a further member of the naturally occurring ecteinascidin family with potential antitumor therapeutic activity.
[0110] The preferred method of producing ecteinascidin 736 and related compounds with different substituents in the tetrahydro-β-carboline unit and in the position 18 (—OR 4 ) are described below in the following reaction scheme.
[0111] As illustrated in Scheme 1, intermediate 36 can be converted to ET-736 (or a substituted derivative) in two steps.
[0112] The first step for producing the preferred compounds type I of the present invention from compound 36 is the introduction of the tetrahydro-β-carboline unit by reaction with the corresponding primary or secondary amine.
[0113] The second step is the transformation of the CN group into an OH group by reaction with silver nitrate in ACN/H 2 O.
[0114] Also is possible to obtain new derivatives with different substituent groups (—OR 4 , position 18 and ═NR 5 ) trough a acylation or alkylation reaction from the preferred compounds I. In all theses cases R 1 and R 2 in the starting material is an hydrogen atom. From the same intermediate and through an alkylation reaction with allyl bromide or an acylation reaction with vinylchloroformiate it can be obtained N and O allylated and N and O vinyl derivatives. All these compounds by reaction with silver nitrate lead to the final products wherein the CN group is transformed into an OH group.
[0115] As the skilled artisan will readily appreciate, the reaction scheme described herein may be modified by use of a wide range of substituted primary amines to produce a series of substituted ecteinascidin 736 derivatives and the compounds generated therefore are to be considered as being part of this invention.
[0116] In particular the reaction conditions can be varied to suit other combinations of the substituent groups in the tetrahydro-β-carboline unit.
[0117] The preferred method of producing ecteinascidin 694 and related compounds with different substituents in the position 5 and 18 (—OR 6 and —OR 7 ) are described below in the following reaction scheme.
[0118] In Scheme 2 the hydrolisis of the acetyl group in C-5 in basic conditions allows to prepare the intermediate with the hydroxyl group in this position. From this compound and by an acylation reaction with anhydrides, acid chlorides or carboxylic acids are prepared new derivatives mono-O sustitued and mono and di-O sustitued (in C-5 and C-18). The reaction to tranform the CN group into the OH is performed in the classic conditions (silver nitrate in CH 3 CN/H 2 O). On the other hand Et-694 can be obtained from Et-736 through the hydrolisis of the acetyl group in C-5 with KOH/MeOH.
[0119] As the skilled artisan will readily appreciate, the reaction scheme described herein may be modified by use of a wide range of substituted primary amines to produce a series of substituted ecteinascidin 736-CN derivatives and the compounds generated therefore are to be considered as being part of this invention.
[0120] In particular the reaction conditions can be varied to suit other combinations of the substituent groups in the tetrahydro-β-carboline unit and in positions C-5 and C-18.
[0121] The present invention will be further illustrated with reference to the following examples which aid in the understanding, but which are not to be construed as limitations thereof.
Experimental Part
[0000] Scheme 1
[0122] Method 1.
[0123] To a solution of 1 equiv. of starting material in acetic acid (5.33 E-5M) under. argon at room temperature was added 3.5 equiv. of tryptamine. The reaction mixture was stirred during 24 h and then the acetic acid was evaporated. An aqueous saturated solution of NaHCO 3 was added and the mixture was extracted with CH 2 Cl 2 and the organic layers were dried over Na 2 SO 4 . Flash chromatography gives pure compounds.
[0124] Method 2
[0125] To a solution of 1 equiv. of compound 1 in CH 2 Cl 2 (0.032M) under Argon at room temperature were added 2 equiv. of Et3N and 2 equiv. of the butyiyl chloride or Boc anhydride (3 equiv.) or vinylchloroformiate. The reaction was followed by TLC and quenched with an aqueous saturated solution of NaHCO 3 , extracted with CH 2 Cl 2 and the organic layers dried over Na 2 SO 4 . Flash chromatography gives pure compound.
[0126] Method 3
[0127] To a solution of 1 equiv. of compound 1 in DMF (0.032M) under Argon at room temperature were added 3 equiv. of CS 2 CO 3 and 3 equiv. of the allyl bromide. The reaction was followed by TLC and quenched with an aqueous saturated solution of NaHCO 3 , extracted with CH 2 Cl 2 and the organic layers dried over Na 2 SO 4 . Flash chromatography gives a mixture of two pure compounds: compound 24 (ET-736-CN-All) and compound 25 (ET-736-CN-diAll).
[0128] Method 4
[0129] To a solution of 1 equiv. of starting material in CH 3 CN/H 2 O 3:2 (0.009M) were added 30 equiv. of AgNO 3 . After 24 h the reaction was quenched with a mixture 1:1 of saturated solutions of brine and NaHCO 3 , stirred for 10 min and diluted and extracted with CH 2 Cl 2 . The organic layer was dried with Na 2 SO 4 . Chromatography gives pure compounds.
Method 1:
[0130] Compound 1: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.74 (s, 1H); 7.38 (d, 1H); 7.25 (d, 1H); 7.08 (t, 1H); 7.00 (t, 1H); 6.66 (s, 1H); 6.22 (d, 1H); 6.02 (d, 1H); 5.79 (s, 1H); 5.08(d, 1H); 4.55(s, 1H); 4.32(s, 1H); 4.27(d, 1H); 4.21(s, 1H); 4.19(d, 1H); 3.81(s, 3H); 3.44-3.40(m, 2H); 3.18-2.78(m, 4H); 2.71-2.51(m, 3H); 2.37(s, 3H); 2.26(s, 3H); 2.21(s, 3H); 2.06 (s, 3H).
[0131] 13 C-NMR (75 MHz, CDCl 3 ): δ 171.7, 168.9, 148.2, 145.9, 143.2, 141.3, 140.5, 135.7, 130.8, 130.6, 129.5, 127.0, 122.2, 120.9, 120.8, 119.5, 118.6, 118.4, 113.8, 111.1, 110.5, 102.2, 62.5, 61.5, 60.8, 60.5, 59.7, 55.9, 54.8, 42.1, 41.7, 40.0, 39.5, 29.9, 24.0, 21.7, 20.8, 16.1, 9.9. ESI-MS m/z: Calcd. for C 41 H 41 N 5 O 8 S: 763.3 Found (M+H + ): 764.2.
[0132] Compound 2: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.64(s, 1H); 7.12 (d, 1H); 6.81 (d, 1H); 6.73 (dd, 1H); 6.65 (s, 1H); 6.19 (s, 1H); 6.00 (s, 1H); 5.79 (s, 1H); 5.0 (d, 1H); 4.54 (s, 1H); 4.30 (s, 1H); 4.27 (d, 1H); 4.20 (s, 1H); 4.18 (d, 1H); 3.80 (s, 3H); 3.78 (s, 3H); 3.43-3.40 (m, 2H); 3.18-2.77 (m, 4H); 2.66-2.49 (m, 3H); 2.37 (s, 3H); 2.34-2.20 (m, 1H); 2.26 (s, 3H); 2.21 (s, 3H); 2.05 (s, 3H).
[0133] 13 C-NMR (75 MHz, CDCl 3 ): δ 171.4, 168.6, 153.7, 148.0, 145.6, 142.9, 141.0, 140.2, 131.1, 130.6, 130.5, 129.2, 127.0, 120.6, 120.5, 118.2, 113.6, 111.9, 111.6, 110.0, 102.0, 100.3, 62.3, 61.2, 60.5, 60.2, 59.4, 55.7, 54.6, 54.5, 41.8, 41.4, 39.7, 39.2, 31.5, 29.6, 23.8, 22.6, 21.5, 20.5, 15.8, 14.4, 9.7. ESI-MS m/z: Calcd. for C 42 H 43 N 5 O 9 S: 793.3 Found (M+H + ): 794.7.
[0134] Compound 3: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.85(s, 1H); 7.45-7.36(m, 5H); 7.01(t, 1H); 6.91(t, 1H); 6.65-6.63(m, 2H); 5.87(s, 1H); 5.77(s, 1H); 5.63(s, 1H); 5.13(s, 2H); 5.05(d, 1H); 4.53(s, 1H); 4.27-4.19(m, 4H); 3.80(s, 3H); 3.46-3.39(m 2H); 3.06-2.79(m, 4H); 2.68-2.50(m 2H); 2.42-2.20(m, 1H); 2.36(s, 3H); 2.27(s, 3H); 2.20(s, 3H); 2.03(s, 3H).
[0135] ESI-MS m/z: Calcd. for C 48 H 47 N 5 O 9 S: 869.3 Found (M+H + ): 870.3.
[0136] Compound 4: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.36(s, 1H); 7.44-7.25(m 5H); 7.13(d, 1H); 6.91(d, 1H); 6.82(dd, 1H); 6.65(s, 1H); 6.21(d, 1H); 6.01(d, 1H); 5.80(s, 1H); 5.08(d, 1H); 5.03(s, 2H); 4.55(s, 1H); 4.31(s, 1H); 4.27(d, 1H); 4.20-4.10(m, 3H); 3.81(s, 3H); 3.44-3.40(m 2H); 3.18-2.77(m, 4H); 2.60-2.46(m, 2H); 2.37(s, 3H); 2.35-2.19(m, 1H); 2.26(s, 3H); 2.21(s, 3H); 2.06(s, 3H).
[0137] ESI-MS m/z: Calcd. for C 48 H 47 N 5 O 9 S: 869.3 Found (M+H + ): 870.3.
[0138] Compound 5: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.63(s, 1H); 7.15-7.11(m, 2H); 6.91(dd, 1H); 6.65(s, 1H); 6.21(d, 1H); 6.01(s, 1H); 5.78(s, 1H); 5.07(d, 1H); 4.54(s, 1H); 4.31(s, 1H); 4.27(d, 1H); 4.21-4.16(m, 2H); 3.81(s, 3H); 3.44-3.40(m,, 2H); 3.17-2.77(m, 4H); 2.66-2.46(m, 3H); 2.31(s, 6H); 2.26(s, 3H); 2.21(s, 3H); 2.06(s, 3H).
[0139] ESI-MS m/z: Calcd. for C 42 H 43 N 5 O 8 S: 777.3 Found (M+Na + ): 800.7.
[0140] Compound 6: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.66(s, 1H); 6.95(d, 1H); 6.64(s, 2H); 6.56(dd, 1H); 6.15(s, 1H); 5.97(s, 1H); 5.81(s, 1H); 5.06(d, 1H); 4.53(s, 1H); 4.29(s, 1H); 4.26(d, 1H); 4.19(s, 1H); 4.17(d, 1H); 3.80(s, 3H); 4.41-3.39(m, 2H); 3.12-2.73(m, 4H); 2.55-2.27(m, 3H); 2.36(s, 3H); 2.25(s, 3H); 2.20(s, 3H); 2.04(s, 3H).
[0141] ESI-MS m/z: Calcd. for C 41 H 41 N 5 O 9 S: 779.3 Found (M+H + ): 780.3.
[0142] Compound 7: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.75(s, 1H); 7.26(dd, 1H); 6.93(dd, 1H); 6.76(ddd, 1H); 6.65(s, 1H); 6.22(d, 1H); 6.01(d, 1H); 5.79(s, 1H); 5.08(d, 1H); 4.55(s, 1H); 4.31(s, 1H); 4.25(d, 1H); 4.20(s, 1H); 4.18(dd, 1H); 3.80(s, 3H); 3.43-3.40(m, 2H); 3.18-2.77(m, 4H); 2.64-2.50(m, 3H); 2.36(s, 3H); 2.26(s, 3H); 2.21(s, 3H); 2.06(s, 3H).
[0143] ESI-MS. m/z: Calcd. for C 41 H 40 FN 5 O 8 S: 781.3 Found (M+H + ): 782.3.
[0144] Compound 8: 1 H-NMR (300 MHz, CDCl 3 ): δ 6.93(d, 1H); 6.80(s, 1H); 6.73(s, 1H); 6.67(dd, 1H); 6.46(s, 1H); 6.20(s, 1H); 6.06(s, 1H); 5.72(s, 1H); 4.96(d, 1H); 4.45(s, 1H); 4.37(d, 1H); 4.25(d, 1H); 4.05-4.01(m, 2H); 3.79(s, 3H); 3.63(d, 1H); 3.39(d, 1H); 3.03-3.91(m, 2H); 2.76-2.34(m, 5H); 3.30(s, 3H); 2.28(s, 3H); 2.21(s, 3H); 2.18(s, 3H); 2.04(s, 3H).
[0145] ESI-MS m/z: Calcd. for C 42 H 43 N 5 O 9 S: 793.3 Found (M+H + ): 794.3.
[0146] Compound 9: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.63(s, 1H); 7.24(d, 1H); 6.75(d, 1H); 6.66(dd, 1H); 6.65(s, 1H); 6.20(s, 1H); 6.00(s, 1H); 5.79(s, 1H); 5.07(d, 1H); 4.54(s, 1H); 4.31(s, 1H); 4.27(d, 1H); 4.20(d, 1H); 4.17(dd, 1H); 3.80(s, 3H); 3.71(s, 3H); 3.43-3.40(m, 2H); 3.16-2.78(m, 4H); 2.64-2.49(m, 3H); 2.36(s, 3H); 2.25(s, .3H); 2.21(s, 3H); 2.06(s, 3H).
[0147] ESI-MS m/z: Calcd. for C 42 H 43 N 5 O 9 S: 793.3 Found (M+H + ): 794.3.
[0148] Compound 10: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.76 (s, 1H); 7.14 (dd, 1H); 7.00 (dd, 1H); 6.81 (ddd, 1H); 6.65 (s, 1H); 6.21 (d, 1H); 6.00 (d, 1H); 5.79 (s, 1H); 5.07 (d, 1H); 4.55 (s, 1H); 4.31 (s, 1H); 4.27 (dd, 1H); 4.20 (d, 1H); 4.18 (dd, 1H); 3.80(s, 3H); 3.44-3.40 (m, 2H); 3.16-2.77 (m, 4H); 2.64-2.44 (m, 3H); 2.37 (s, 3H); 2.26 (s, .3H); 2.21 (s, 3H); 2.05 (s, 3H).
[0149] ESI-MS m/z: Calcd. for C 41 H 40 FN 5 O 8 S: 781.3 Found (M+H + ): 782.1.
[0150] Compound 11: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.48 (s, 1H); 7.22 (d, 1H); 6.96-6.88 (m, 2H); 6.65 (s, 1H); 6.15 (d, 1H); 6.04 (d, 1H); 5.78 (s, 1H); 5.09 (d, 1H); 4.55 (s, 1H); 4.34 (s, 1H); 4.28-4.20 (m, 3H); 3.81 (s, 3H); 3.48 (d, 1H); 3.42 (d, 1H); 3.12-2.78 (m, 4H); 2.69-2.43 (m, 3H); 2.37 (s, 3H); 2.36 (s, 3H); 2.28 (s, .3H); 2.21 (s, 3H); 2.06 (s, 3H).
[0151] ESI-MS m/z: Calcd. for C 42 H 43 N 5 O 8 S: 777.3 Found (M+H + ): 778.3
[0152] Compound 12 (first isomer): 1 H-NMR (300 MHz, CDCl 3 ): δ 7.68 (s, 1H); 7.05 (d, 1H); 6.63-6.57 (m, 3H); 6.22 (d, 1H); 6.02 (d, 1H); 5.73 (s, 1H); 5.12 (d, 1H); 4.58 (s, 1H); 4.36 (s, 1H); 4.34-4.22 (m, 3H); 3.80 (s, 3H); 3.47-3.42 (m, 2H); 3.05-2.86 (m, 2H); 2.67-2.35 (m, 2H); 2.32-2.05 (m, 3H); 2.31 (s, 3H); 2.28 (s, 3H); 2.15 (s, 3H); 2.03 (s, 3H); 1.07 (d, 3H).
[0153] ESI-MS m/z: Calcd. for C 42 H 43 N 5 O 9 S: 793.2-Found (M+H + ): 794.2.
[0154] Compound 13 (second isomer): 1 H-NMR (300 MHz, CDCl 3 ): δ 7.54 (s, 1H); 7.08 (d, 1H); 6.73 (d, 1H); 6.63 (dd, 1H); 6.57 (s, 1H); 6.20 (d, 1H); 6.00 (d, 1H); 5.74 (s, 1H); 5.02 (d, 1H); 4.60 (s, 1H); 4.33 (s, 1H); 4.27 (d, 1H); 4.22 (d, 1H); 4.12 (dd, 1H); 3.80 (s, 3H); 3.44-3.32 (m, 3H); 3.05-2.89 (m, 2H); 2.49-2.03 (m, 4H); 2.32 (s, 3H); 2.24 (s, 3H); 2.18 (s, .3H); 2.07 (s, 3H); 1.21 (d, 3H).
[0155] ESI-MS m/z: Calcd. for C 42 H 43 N 5 O 9 S: 793.2 Found (M+H + ): 794.2.
[0156] Compound 14 (first isomer): 1 H-NMR (300 MHz, CDCl 3 ): δ 7.98 (s, 1H); 7.40 (dd, 1H); 6.18 (t, 1H); 7.04 (t, 1H); 6.82 (s, 1H); 6.16 (d, 1H); 6.01 (d, 1H); 5.74 (s, 1H); 4.95 (d, 1H); 4.64 (s, 1H); 4.40 (s, 1H); 4.30-4.24 (m, 3H); 3.62 (s, 3H); 3.56 (d, 1H); 3.50 (d, 1H); 3.12-2.89 (m, 4H); 2.75-2.51 (m, 3H); 2.43 (s, 3H); 2.38-2.30 (m, 2H); 2.26 (s, 3H); 2.19 (s, 3H); 2.08 (s, 3H); 2.00 (s, 3H).
[0157] ESI-MS m/z: Calcd. for C 42 H 43 N 5 O 8 S: 777.2 Found (M+H + ): 778.2.
[0158] Compound 15 (second isomer): 1 H-NMR (300 MHz, CDCl 3 ): δ 7.36 (d, 1H); 7.15-7.06 (m, 2H); 7.01 (ddd, 1H); 6.93 (s, 1H); 6.47 (s, 1H); 6.22 (d, 1H); 6.09 (d, 1H); 5.72 (s, 1H); 4.97 (d, 1H); 4.46 (s, 1H); 4.40 (d, 1H); 4.26 (dd, 1H); 4.03 (dd, 1H); 4.02 (s, 1H); 3.80 (s, 3H); 3.63 (d, 1H); 3.39 (d, 1H); 3.00-2.92 (m, 2H); 277-2.54 (m, 4H); 2.30 (s, 3H); 2.26-2.25 (m, 2H); 2.23 (s, 6H); 2.19 (s, 3H); 2.05 (s, 3H).
[0159] ESI-MS m/z: Calcd. for C 42 H 43 N 5 O 8 S: 777.2 Found (M+H + ): 778.2.
[0160] Compound 16 (first isomer): 1 H-NMR (300 MHz, CDCl 3 ): δ 7.82 (s, 1H); 7.14 (dd, 1H); 6.96 (dd, 1H); 6.82 (ddd, 1H); 6.61 (s, 1H); 6.23 (d, 1H); 6.02 (d, 1H); 5.72 (s, 1H); 5.12 (d, 1H); 4.59 (s, 1H); 4.37 (s, 1H); 4.32-4.25 (m, 3H); 3.80 (s, 3H); 3.48-3.43 (m, 2H); 3.05-2.86 (m, 4H); 2.78-2.70 (m, 1H); 2.60-2.34 (m, 3H); 2.31 (s, 3H); 2.27 (s, 3H); 2.16 (s, 3H); 2.03 (s, 3H); 1.12 (d, 3H).
[0161] ESI-MS m/z: Calcd. for C 42 H 42 FN 5 O 8 S: 795.3 Found (M+H + ): 796.2.
[0162] Compound 17 (second isomer): 1 H-NMR (300 MHz, CDCl 3 ): δ 7.65 (s, 1H); 7.18 (dd, 1H); 6.99 (dd, 1H); 6.83 (ddd, 1H); 6.58 (s, 1H); 6.22 (d, 1H); 6.01 (d, 1H); 5.74 (s, 1H); 5.03 (d, 1H); 4.61 (s, 1H); 4.34 (s, 1H); 4.27 (d, 1H); 4.22 (d, 1H); 4.14-4.10 (m, 1H); 3.80(s, 3H); 3.44 (d, 2H); 3.38-3.30 (m, 1H); 3.06-2.99 (m, 2H); 2.50 (dd, 1H); 2.43 (d, 1H); 2.32 (s, 3H); 2.24 (s, 3H); 2.18 (s, 3H); 2.16-2.11 (m, 2H); 2.08 (s, 3H); 1.20 (d, 3H).
[0163] ESI-MS m/z: Calcd. for C 42 H 42 FN 5 O 8 S: 795.3 Found (M+H + ): 796.2.
[0164] Compound 18 (first isomer): 1 H-NMR (300 MHz, CDCl 3 ): δ 7.83 (s, 1H); 7.34 (d, 1H); 7.24 (d, 1H); 7.09 (ddd, 1H); 7.00 (ddd, 1H); 6.62 (s, 1H); 6.24 (d, 1H); 6.03 (d, 1H); 5.73 (s, 1H); 5.13 (d, 1H); 4.59 (s, 1H); 4.38 (s, 1H); 4.33-4.27 (m, 3H); 3.80(s, 3H); 3.48-3.43 (m, 2H); 3.06-2.87 (m, 2H); 2.78-2.72 (m, 1H); 2.61-2.24 (m, 4H); 2.32 (s, 3H); 2.27 (s, .3H); 2.16 (s, 3H); 2.03 (s, 3H); 1.13 (d, 3H).
[0165] ESI-MS m/z: Calcd. for C 42 H 43 N 5 O 8 S: 777.2 Found (M+H + ): 778.2.
[0166] Compound 19 (second isomer): 1 H-NMR (300 MHz, CDCl 3 ): δ 7.66 (s, 1H); 7.37 (d, 1H); 7.28 (d, 1H); 7.10 (ddd, 1H); 7.00 (ddd, 1H); 6.58 (s, 1H); 6.24 (d, 1H); 6.02 (d, 1H); 5.75 (s, 1H); 5.03 (d, 1H); 4.61 (s, 1H); 4.35 (s, 1H); 4.28 (dd, 1H); 4.23 (d, 1H); 4.15-4.08 (m, 1H); 3.81 (s, 3H); 3.44 (d, 2H); 3.38-3.32 (m, 1H); 3.07-2.90 (m, 2H); 2.58 (dd, 1H); 2.45 (d, 1H); 2.33 (s, 3H); 2.27-2.12 (m, 2H); 2.24 (s, .3H); 2.19 (s, 3H); 2.08 (s, 3H); 1.20 (d, 3H).
[0167] ESI-MS m/z: Calcd. for C 42 H 43 N 5 O 8 S: 777.2 Found (M+H + ): 778.2.
[0168] Method 2:
[0169] Compound 20: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.70 (s, 1H); 7.38 (d, 1H); 7.25 (d, 1H); 7.10 (ddd, 1H); 7.02 (ddd, 1H); 7.01 (s, 1H); 6.24 (d, 1H); 6.03 (d, 1H); 5.09 (d, 1H); 4.44 (s, 1H); 4.33 (s, 1H); 4.22-4.18 (m, 2H)-3.81 (d, 1H); 3.77 (s, 3H); 3.48-3.44 (m, 2H); 3.19-2.81 (m, 4H); 2.70-2.48 (m, 3H); 2.62 (t, 2H); 2.37 (s, 3H); 2.34-2.15 (m, 2H); 2.29 (s, .3H); 2.18 (s, 3H); 2.04 (s, 3H); 1.95-1.82 (m, 2H); 1.10 (t, 3H).
[0170] ESI-MS m/z: Calcd. for C 45 H 47 N 5 O 9 S: 833.3 Found (M+H + ): 834.2.
[0171] Compound 21: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.70 (s, 1H); 7.38 (d, 1H); 7.24 (d, 1H); 7.09 (ddd, 1H); 7.00 (ddd, 1H); 6.99 (s, 1H); 6.22 (d, 1H); 6.02 (d, 1H); 5.08 (d, 1H); 4.48 (s, 1H); 4.32 (s, 1H); 4.25-4.21 (m, 2H) 3.81 (s, 3H); 3.46-3.44 (m, 2H); 3.18-2.79 (m, 4H); 2.72-2.43 (m, 3H); 2.36 (s, 3H); 2.31 (s, .3H); 2.20 (s, 3H); 2.08 (s, 3H); 1.54 (s, 9H).
[0172] ESI-MS m/z: Calcd. for C 46 H 49 N 5 O 10 S: 863.3 Found (M+H + ): 864.2.
[0173] Compound 22: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.70 (s, 1H); 7.38 (d, 1H); 7.26-6.99 (m, 5H); 6.24 (d, 1H); 6.03 (d, 1H); 5.09 (d, 1H); 5.00 (dd, 1H); 4.71 (dd, 1H); 4.48 (s, 1H); 4.33 (s, 1H); 4.24-4.21 (m, 2H) 3.95 (d, 1H); 3.81 (s, 3H); 3.48-3.45 (m, 2H); 3.18-2.81 (m, 4H); 2.72-2.45 (m, 3H); 2.38 (s, 3H); 2.34 (s, .3H); 2.30-2.11 (m, 2H); 2.20 (s, 3H); 2.08 (s, 3H).
[0174] ESI-MS m/z: Calcd. for C 44 H 43 N 5 O 10 S: 833.3 Found (M+H + ): 834.2.
[0175] Compound 23: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.38 (d, 1H); 7.20-7.13 (m, 3H); 7.07-6.98 (m, 2H); 6.88 (s, 1H); 6.66 (s, 1H); 6.18 (d, 1H); 6.12 (d, 1H); 4.95 (dd, 1H); 4.79-(d, 1H); 4.78 (dd, 1H); 4.68 (dd, 1H); 4.46 (dd, 1H); 4.40 (d, 1H); 4.34-4.18 (m, 3H) 3.97 (d, 1H); 3.89 (d, 1H); 3.85 (s, 3H); 3.61 (d, 1H); 3.41 (d, 1H); 3.17-2.98 (m, 3H); 2.76-2.42 (m, 4H); 2.37 (s, 3H); 2.32 (s, 3H); 2.18 (s, 3H); 2.13 (s, 3H).
[0176] ESI-MS m/z: Calcd. for C 47 H 45 N 5 O 12 S: 903.2 Found (M+Na + ): 926.1
[0177] Method 3:
[0178] Compound 24: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.71 (s, 1H); 7.38 (d, 1H); 7.24 (d, 1H); 7.09 (ddd, 1H); 7.00 (ddd, 1H); 6.86 (s, 1H); 6.22 (d, 1H); 6.16-6.04 (m, 1H); 6.02 (d, 1H); 5.47 (dd, 1H); 5.26 (dd, 1H); 5.09 (d, 1H); 4.83 (dd, 1H); 4.52 (s, 1H); 4.36 (dd, 1H); 4.32 (s, 1H); 4.24-4.19 (m, 3H); 3.84 (s, 3H); 3.45-3.41 (m, 2H); 3.18-2.79 (m, 4H); 2.73-2.47 (m, 3H); 2.33 (s, 3H); 2.31-2.26 (m, 1H); 2.24 (s, 3H); 2.21 (s, 3H); 2.06 (s, 3H); 2.03 (d, 1H).
[0179] ESI-MS m/z: Calcd. for CMH 45 N 5 O 8 S: 803.3 Found (M+H + ): 804.3
[0180] Compound 25: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.39 (d, 1H); 7.25-7.23 (m, 1H); 7.096.98 (m, 3H); 6.80 (s, 1H); 6.14-6.00 (m, 1H); 6.10 (d, 1H); 6.02 (d, 1H); 5.60-5.40 (m, 1H); 5.45 (dd, 1H); 5.25 (dd, 1H); 5.02-4.95 (m, 2H); 4.81 (dd, 1H); 4.73-4.62 (m, 1H); 4.55 (s, 1H); 4.37-4.16 (m, 6H); 3.84 (s, 3H); 3.51 (d, 1H); 3.45-3.38 (m, 2H); 3.05-2.89 (m, 3H); 2.70-2.50 (m, 3H); 2.33-2.16 (m, 2H); 2.31 (s, 3H); 2.23 (s, .3H); 2.21 (s, 3H); 2.03 (s, 3H).
[0181] ESI-MS m/z: Calcd. for C 47 H 49 N 5 O 8 S: 843.3 Found (M+H + ): 844.2
Method 4:
[0182] Compound 26: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.70 (s, 1H); 7.38 (d, 1H); 7.24 (d, 1H); 7.08 (t, 1H); 7.00 (t, 1H); 6.67 (s, 1H); 6.20 (d, 1H); 5.99 (d, 1H); 5.74 (s, 1H); 5.20 (d, 1H); 4.82 (s, 1H); 4.347-4.38 (m, 3H); 4.16-4.10 (m, 2H); 3.81 (s, 3H); 3.49 (d, 1H); 3.22-3.13 (m, 2H); 3.00 (d, 1H); 2.88-2.79 (m, 2H); 2.71-2.52 (m, 3H); 2.37 (s, 3H); 2.28-2.24 (m, 1H); 2.25 (s, 3H); 2.19 (s, 3H); 2.05 (s, 3H).
[0183] 13 C-NMR (75 MHz, CDCl 3 ): δ 171.4, 168.7, 147.8, 145.4, 142.8, 141.0, 140.6, 135.4, 131.2, 130.9, 129.0, 126.8, 121.8, 121.3, 120.9, 119.1, 118.3, 118.1, 115.5, 112.8, 110.8, 110.1, 101.7, 81.9, 62.3, 61.8, 60.2.57.6, 57.4, 55.8, 54.9, 42.1, 41.2, 39.7, 39.2, 31.5, 23.5, 22.6, 21.5, 20.5, 15.8, 14.0, 9.6.
[0184] ESI-MS m/z: Calcd. for C 40 H 42 N 4 O 9 S: 754.3 Found (M-H 2 O+H + ): 737.2.
[0185] Compound 27: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.59 (s, 1H); 7.13 (d, 1H); 6.81 (s, 1H); 6.73 (dd, 1H); 6.67 (s, 1H); 6.19 (d, 1H); 5.99 (d, 1H); 5.74 (s, 1H); 5.19 (d, 1 H); 4.82 (s, 1H); 4.49-4.47 (m, 2H); 4.16-4.09 (m, 2H); 3.81 (s, 3H); 3.79 (s, 3H); 3.50-3.45 (m, 2H); 3.24-3.13 (m, 2H); 3.02 (d, 1H); 2.88-2.79 (m, 2H); 2.67-2.48 (m, 3H); 2.37 (s, 3H); 2.30-2.24 (m, 1H); 2.25 (s, 3H); 2.19 (s, 3H); 2.04 (s, 3H).
[0186] 13 C-NMR (75 MHz, CDCl 3 ): δ 171.6, 154.0, 148.1, 145.6, 143.1, 141.3, 140.9, 131.9, 131.4, 130.8, 129.3, 127.4, 121.5, 121.2, 115.7, 113.1, 112.1, 111.8, 110.1, 102.0, 100.6, 82.1, 62.6, 62.0, 60.5, 57.9, 57.6, 56.1, 56.0, 55.2, 42.4, 41.5, 40.0, 39.4, 31.8, 29.9, 23.8, 22.8, 21.8, 20.8, 16.0, 14.6, 9.9.
[0187] ESI-MS m /z: Calcd. for C 40 H 42 N 4 O 9 S: 784.4 Found (M-H 2 O+H + ): 767.2.
[0188] Compound 28: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.81 (s, 1H); 7.43-7.36 (m, 5H); 7.01 (d, 1H); 6.91 (t, 1H); 6.66 (s, 1H); 6.63 (d, 1H); 5.84(s, 1H); 5.75 (s, 1H); 5.60 (s, 1H); 5.20-5.09 (m, 3H); 4.78 (s, 1H); 4.49 (d, 1H); 4.44 (s, 1H); 4.16 (s, 1H); 4.14-4.12 (m, 1H); 3.81 (s, 3H); 3.52 (d, 1H); 3.47 (s, 2H); 3.22-2.80 (m, 5H); 2.68-2.51 (m, 2H); 2.36 (s, 3H); 2.39-2.21 (m, 1H); 2.27 (s, 3H); 2.18 (s, 3H); 2.02 (s, 3H).
[0189] 13 C-NMR (75 MHz, CDCl 3 ): δ 171.4, 148.0, 145.6, 145.2, 143.1, 141.1, 140.8, 137.3, 131.6, 130.7, 129.3, 128.8, 128.5, 128.2, 128.0, 126.2, 121.4, 121.3, 119.8, 118.1, 115.5, 113.0, 111.8, 111.0, 103.8, 101.8, 82.1, 70.6, 62.9, 61.9, 60.5, 58.0, 57.7, 56.1, 55.1, 42.3, 41.5, 40.0, 39.5, 29.9, 23.9, 22.0, 20.7, 16.0, 9.8.
[0190] ESI-MS m/z: Calcd. for C 47 H 48 N 4 O 10 S: 860.3 Found (M-H 2 O+H + ): 843.3
[0191] Compound 29: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.59 (s, 1H); 7.44-7.25 (m, 5H); 7.13 (d, 1H); 6.91 (s, 1H); 6.82 (d, 1H); 6.66 (s, 1H); 6.19 (s, 1H); 5.98 (s, 1H); 5.75 (s, 1H); 5.19 (d, 1H); 5.03 (s, 2H); 4.82 (s, 1H); 4.49-4.47 (m, 2H); 4.17-4.09 (m, 2H); 3.81 (s, 3H); 3.49-3.47 (m, 2H); 3.24-2.80 (m, 5H); 2.64-2.50 (m, 3H); 2.37 (s, 3H); 2.25 (s, 3H); 2.19 (s, 3H); 2.05 (s, 3H).
[0192] 13 C-NMR (75 MHz, CDCl 3 ): δ 171.4, 168.6, 153.2, 148.1, 145.7, 143.1, 141.3, 140.9, 137.9, 131.0, 129.7, 128.6, 127.9, 127.8, 127.4, 121.2, 115.7, 112.8, 111.8, 110.2, 102.3, 102.0, 82.1, 71.1, 62.5, 62.0, 60.5, 58.0, 57.6, 56.1, 55.2, 42.4, 41.5, 40.0, 39.4, 32.1, 29.9, 29.5, 23.8, 22.9, 21.8, 20.8, 16.0, 14.6, 9.9.
[0193] ESI-MS m/z: Calcd. for C 47 H 48 N 4 O 10 S: 860.3 Found (M-H 2 O+H + ): 843.3
[0194] Compound 30: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.61 (s, 1H); 7.16-7.11 (m, 2H); 6.91 (d, 1H); 6.67 (s, 1H); 6.20 (d, 1H); 5.99 (d, 1H); 5.75 (s, 1H); 5.20 (d, 1H); 4.82 (s, 1H); 4.49 (d, 1H); 4.35 (s, 1H); 4.16 (d, 2H); 4.11 (dd, 1H); 3.81 (s, 3H); 3.48 (s, 1H); 3.23-2.79 (m, 5H); 2.67-2.47 (m, 3H); 2.37 (s, 6H); 2.25 (s, 3H); 2.19 (s, 3H); 2.05 (s, 3H).
[0195] 13 C-NMR (75 MHz, CDCl 3 ): δ 174.5, 171.6, 168.9, 148.1, 145.6, 143.1, 141.3, 140.9, 134.0, 131.2, 128.6, 127.3, 123.6, 121.5, 121.2, 118.3, 115.7, 109.9, 102.0, 82.1, 62.6, 62.0, 60.5, 57.9, 57.7, 56.1, 56.2, 42.4, 41.5, 40.0, 39.4, 29.9, 23.8, 21.7, 21.6, 20.8, 16.0, 9.9.
[0196] ESI-MS m/z: Calcd. for C 41 H 44 N 4 O 9 S: 768.3 Found (M-H 2 O+H + ): 751.3.
[0197] Compound 31: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.60 (s, 1H); 7.00 (d, 1H); 6.69 (d, 1H); 6.66 (s, 1H); 6.69 (dd, 1H); 6.16 (s, 1H); 5.96 (s, 1H); 5.78 (s, 1H); 5.19 (d, 1H); 4.82 (s, 1H); 4.49 (d, 1H); 4.46 (s, 1H); 4.17 (d, 1H); 4.10 (d, 1H); 3.81 (s, 3H); 3.72-3.59 (m, 2H); 3.64 (d, 2H); 3.50 (d, 1H); 3.23-2.76 (m, 4H); 2.55-2.29 (m, 3H); 2.37 (s, 3H); 2.25 (s, 3H); 2.19 (s, 3H); 2.03 (s. 3H).
[0198] 13 C-NMR (75 MHz, CDCl 3 ): δ 171.3, 166.9, 149.2, 147.9, 145.4, 142.9, 141.0, 140.7, 131.2, 130.7, 127.5, 121.2, 120.9, 115.5, 111.5, 103.1, 101.8, 81.9, 62.3, 61.8, 60.3, 57.7, 57.4, 55.8, 54.9, 42.1.41.2, 39.6, 39.1, 29.6, 23.5, 22.6, 21.4, 20.5, 15.8, 14.1, 9.6.
[0199] ESI-MS m/z: Calcd. for C 40 H 42 N 4 O 10 S: 770.3 Found (M-H 2 O+H + ): 753.3.
[0200] Compound 32: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.72 (s, 1H); 7.27 (dd, 1H); 6.94 (dd, 1H); 6.76 (ddd, 1H); 6.66 (s, 1H); 6.20 (s, 1H); 5.99 (s, 1H); 5.75 (s, 1H); 5.19 (d, 1H); 4.83 (s, 1H); 4.49 (d, 1H); 4.16-4.09 (m, 2H); 3.81 (s, 3H); 3.50-3.48 (m, 1H); 3.48 (s, 1H); 3.22-2.79 (m, 5H); 2.65-2.51 (m, 3H); 2.37 (s, 3H); 2.25 (s, 3H); 2.19 (s, 3H); 2.05 (s, 3H).
[0201] 13 C-NMR (75 MHz, CDCl 3 ): δ 171.5, 169.0, 148.1, 145.7, 143.1, 141.3, 140.9, 131.5, 129.3, 123.7, 121.5, 121.1, 119.3, 119.1, 118.3, 115.7, 110.4, 108.2, 107.8, 102.0, 97.8, 97.5, 82.1, 62.4, 62.1, 60.5, 57.9, 57.6, 56.1, 55.1, 42.4, 41.5, 39.9, 39.4, 29.9, 23.8, 21.7, 20.8, 16.0, 9.9.
[0202] ESI-MS m/z: Calcd. for C 40 H 41 FN 4 O 9 S: 772.3 Found (M-H 2 O+H + ): 755.3.
[0203] Compound 33: 1 H-NMR (300 MHz, CDCl 3 ): δ 6.85 (d, 1H); 6.80 (s, 1H); 6.71-6.64 (m, 2H); 6.48 (s, 1H); 6.18 (s, 1H); 6.02 (s, 1H); 5.74 (s, 1H); 5.03 (d, 1H); 4.88 (d, 1H); 4.39 (d, 1H); 4.36 (s, 1H); 4.16 (d, 1H); 3.98 (ddm 1H); 3.80 (s,3H); 3.71 (d, 1H); 3.48 (s, 1H); 3.22 (d, 1H); 2.93-2.83 (m, 2H); 2.73-2.39 (m, 4H); 2.29 (s, 3H); 2.28-2.05 (m, 1H); 2.26 (s, 3H); 2.22 (s, 3H); 2.18 (s, 3H); 2.03 (s, 3H).
[0204] 13 C-NMR (75 MHz, CDCl 3 ): δ 168.9, 149.3, 147.6, 145.5, 142.7, 141.6, 140.7, 131.3, 131.1, 129.3, 126.9, 121.2, 115.7, 111.9, 111.0, 110.7, 103.1, 102.0, 83.4, 69.8, 63.7, 60.2, 58.5, 57.7, 55.1, 54.7, 59.5, 43.1, 41.4, 40.6, 35.0, 29.6, 24.6, 22.6, 21.1, 20.2, 15.5, 9.7.
[0205] ESI-MS m/z: Calcd. for C 41 H 44 N 4 O 10 S: 784.3 Found (M-H 2 O+H + ): 767.3.
[0206] Compound 34: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.58 (s, 1 H); 7.23 (d, 1H); 6.76 (d, 1H); 6.67 (dd, 1 H); 6.66 (s, 1 H); 6.19 (d, 1H); 5.98 (d, 1H); 5.74 (s, 1H); 5.20 (d, 1H); 4.82 (s, 1H); 4.49 (d, 1H); 4.47 (s, 1H); 4.16 (d, 1H); 4.10 (dd, 1 H); 3.81 (s, 3H); 3.78 (s, 3H); 3.51-3.47 (m, 1H); 3.22-2.80 (m, 5H); 2.65.2.50 (m, 3H); 2.36 (s, 3H); 2.25 (s, 3H); 2.19 (s, 3H); 2.05 (s, 3H).
[0207] 13 C-NMR (75 MHz, CDCl 3 ): δ 171.7, 168.9, 156.5, 148.1, 145.6, 143.1, 141.3, 140.9, 136.5, 131.5, 129.8, 129.3, 121.6, 121.5, 121.2, 119.2, 115.8, 113.1, 110.3, 109.3, 102.2, 94.9, 82.2, 62.5, 62.0, 60.5, 57.9, 57.7, 56.1, 55.8, 55.2, 42.3, 41.5, 40.0, 39.5, 29.9, 23.8, 21.8, 20.8, 16.0, 9.9.
[0208] ESI-MS m/z: Calcd. for C 41 H 44 N 4 O 10 S: 784.3 Found (M-H 2 O+H + ): 767.3.
[0209] Compound 35: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.73 (s, 1H); 7.15 (dd, 1H); 7.00 (dd, 1H); 6.81 (ddd, 1H); 6.67 (s, 1H); 6.20 (d, 1H); 5.99 (d, 1H); 5.76(s, 1H); 5.19 (d, 1H); 4.83 (s, 1H); 4.49 (d, 2H); 4.17 (d, 1H); 4.12 (dd, 1H); 3.81(s, 3H); 3.65-3.64 (m, 1H); 3.50 (d, 1H); 3.24-2.12 (m, 2H); 3.00 (d, 1H); 2.89-2.80 (m, 2H); 2.66-2.45 (m, 3H); 2.37 (s, 3H); 2.25 (s, 3H); 2.20 (s, 3H); 2.05 (s, 3H).
[0210] 13 C-NMR (75 MHz, CDCl 3 ): δ 171.4, 169.0, 159.4, 156.3, 148.1, 145.7, 143.1, 141.3, 140.9, 138.0, 132.2, 129.4, 127.4, 127.3, 121.4, 121.4, 121.2, 118.2, 115.7, 113.1, 111.8, 111.7, 110.4, 110.1, 103.7, 103.4, 102.0, 82.1, 62.5, 62.1, 60.5, 57.9, 57.6, 56.1, 55.1, 42.3, 41.4, 39.9, 39.4, 29.9, 23.8, 21.7, 20.8, 16.0, 9.9.
[0211] ESI-MS m/z: Calcd. for C 40 H 41 FN 4 O 9 S: 772.2 Found (M-H 2 O+H + ): 755.2.
[0212] Compound 36: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.47 (s, 1H); 7.22 (d, 1H); 6.95-6.87 (m, 2H); 6.66 (s, 1H); 6.13 (d, 1H); 6.01 (d, 1H); 5.76 (s, 1H); 5.20 (d, 1H); 4.84 (s, 1H); 4.49 (d, 1H); 4.46 (s, 1H); 4.18-4.14 (m, 2H); 3.81 (s, 3H); 3.54 (d, 1H); 3.48(s, 1H); 3.22 (d, 1H); 3.20-2.80 (m, 4H); 2.70-2.42 (m, 3H); 2.36(s, 6H); 2.27 (s, 3H); 2.18 (s, 3H); 2.05 (s, 3H).
[0213] 13 C-NMR (75 MHz, CDCl 3 ): δ 171.3, 169.0, 148.0, 145.6, 143.1, 141.4, 140.9, 135.3, 131.5, 131.1, 130.7, 129.4, 126.6, 122.8, 121.8, 121.3, 119.9, 119.6, 118.1, 116.3, 115.8, 102.0, 82.1, 62.1, 60.5, 58.0, 57.8, 56.1, 55.1, 42.4, 41.5, 40.1, 39.6, 29.9, 23.9, 21.9, 20.7, 16.6, 16.0, 9.9.
[0214] ESI-MS m/z: Calcd. for C 41 H 44 N 4 O 9 S: 768.2 Found (M-H 2 O+H + ): 751.2.
[0215] Compound 37 (first isomer): 1 H-NMR ( 300 MHz, CDCl 3 ): δ 7.70 (s, 1H); 7.06 (d, 1H); 6.67-6.61 (m, 3H); 6.20 (d, 1H); 5.98 (d, 1H); 5.70 (s, 1H); 5.20 (d, 1H); 4.86 (s, 1H); 4.53 (d, 1H); 4.48 (s, 1H); 4.18(s, 1H); 3.80(s, 3H); 3.72-3.54 (m, 4H); 3.24-3.22 (m, 1H); 3.01-2.56 (m, 5H); 2.31 (s, 3H); 2.27 (s, 3H); 2.15 (s, 3H); 2.02 (s. 3H); 1.10 (d, 3H).
[0216] ESI-MS m/z: Calcd. for C 41 H 44 N 4 O 10 S: 784.3 Found (M-H 2 O+H + ): 767.3.
[0217] Compound 38 (second isomer): 1 H-NMR (300 MHz, CDCl 3 ): δ 7.51 (s, 1H); 7.10 (d, 1H); 6.75 (d, 1H); 6.64 (dd, 1H); 6.59 (s, 1H); 6.19 (d, 1H); 5.97 (d, 1H); 5.71 (s, 1H); 5.15 (d, 1H); 4.84 (s, 1H); 4.53-4.50 (m, 2H); 4.16 (s, 1H); 4.04 (dd, 1H); 3.80(s, 3H); 3.65-3.63 (m, 1H); 3.51-3.49 (m, 1H); 3.40-2.36 (m, 1H); 3.24-3.21 (m, 1H); 3.03-2.84 (m, 2H); 2.50-2.41 (m, 2H); 2.32 (s, 3H); 2.23 (s, 3H); 2.16 (s, 3H); 2.06 (s. 3H); 1.20 (d, 3H).
[0218] ESI-MS m/z: Calcd. for C 41 H 44 N 4 O 10 S: 784.3 Found (M-H 2 +H + ): 767.3.
[0219] Compound 39 (first isomer): 1 H-NMR (300 MHz, CDCl 3 ): δ 8.09 (s, 1H); 7.41 (d, 1H); 7.17 (t, 1H); 7.03 (t, 1H); 6.87 (d, 1H); 6.83 (s, 1H); 6.13 (d, 1H); 5.98 (d, 1H); 5.69 (s, 1H); 5.02 (d, 1H); 4.88 (s, 1H); 4.55-4.16 (m, 4H); 3.64-3.56 (m, 1H); 3.61 (s, 3H); 3.31-3.29 (m, 1H); 3.22-2.80 (m, 3H); 2.68-2.46 (m, 3H); 2.41 (s, 3H); 2.27 (s, 3H); 2.20 (s, 3H); 2.07 (s, 3H); 1.99 (s, 3H).
[0220] ESI-MS m/z: Calcd. for C 41 H 44 N 4 O 9 S: 768.2 Found (M-H 2 O+H + ): 751.2.
[0221] Compound 40 (second isomer): 1 H-NMR (300 MHz, CDCl 3 ): δ7.36 (d, 1H); 7.12-7.05 (m, 2H); 7.00 (ddd, 1H); 6.92 (s, 1H); 6.48 (s, 1H); 6.20 (d, 1H); 6.06 (d, 1H); 5.70 (s, 1H); 5.04 (d, 1H); 4.88 (s, 1H); 4.39-4.36 (m, 1H); 4.15 (d, 1H); 3.98 (dd, 1H); 3.80 (s, 3H); 3.72-3.64 (m, 2H); 3.21 (d, 1H); 2.95-2.84 (m, 2H); 2.73-2.55 (m, 4H); 2.29 (s, 3H); 2.26 (s, 3H); 2.23 (s, 3H); 2.18 (s, 3H); 2.03 (s, 3H).
[0222] 13 C-NMR (75 MHz, CDCl 3 ): δ 169.1, 167.5, 147.9, 145.7, 142.9, 141.9, 140.9, 136.0, 131.6, 129.4, 126.5, 122.5, 122.1, 121.5, 119.5, 118.7, 116.0, 111.5, 110.6, 102.2, 83.7, 63.9, 60.4, 58.8, 57.9, 55.4, 54.9, 49.7, 43.4, 41.7, 40.8, 32.1, 29.5, 24.9, 22.9, 21.5, 20.5, 15.8, 14.3, 9.9.
[0223] ESI-MS m/z: Calcd. for C 41 H 44 N 4 O 9 S: 768.2 Found (M-H 2 O+H + ): 751.2.
[0224] Compound 41 (first isomer): 1 H-NMR (300 MHz, CDCl 3 ): δ 7.84 (s, 1H); 7.13 (dd, 1H); 6.96 (dd, 1H); 6.81 (ddd, 1H); 6.62 (s, 1H); 6.20 (d, 1H); 5.99 (d, 1H); 5.70 (s, 1H); 5.19 (d, 1H); 4.86 (s, 1H); 4.52 (d, 1H); 4.50 (s, 1H); 4.16 (d, 1H); 3.80 (s, 3H); 3.53 (d, 1H); 3.49-3.48 (m, 1H); 3.23 (d, 1H); 3.00-2.71 (m, 3H); 2.62-2.41 (m, 2H); 2.31 (s, 3H); 2.27 (s, 3H); 2.14 (s, 3H); 2.02 (s, 3H); 1.13 (d, 3H).
[0225] 13 C-NMR (75 MHz, CDCl 3 ): δ 170.5, 168.9, 159.4, 156.2, 147.6, 145.8, 143.0, 141.2, 133.2, 132.2, 131.7, 131.1, 129.2, 129.0, 127.3, 121.7, 115.6, 111.7, 111.6, 110.3, 109.9, 103.7, 103.4, 102.0, 81.8, 64.0, 62.0, 60.5, 58.0, 56.1, 55.3, 44.0, 42.4, 41.5, 38.1, 32.1, 29.5, 24.0, 22.9, 21.7, 20.7, 16.2, 14.3, 9.9.
[0226] ESI-MS m/z: Calcd. for C 41 H 43 FN 4 O 9 S: 786.2 Found (M-H 2 O+H + ): 769.3.
[0227] Compound 42 (second isomer): 1 H-NMR (300 MHz, CDCl 3 ): δ 7.62 (s, 1H); 7.18 (dd, 1H); 6.99 (dd, 1H); 6.82 (ddd, 1H); 6.59 (s, 1H); 6.20 (d, 1H); 5.98 (d, 1H); 5.71 (s, 1H); 5.15 (d, 1H); 4.85 (s, 1H); 4.52(s, 1H); 4.50 (d, 1H); 4.16 (d, 1H); 4.05 (dd, 1H); 3.80 (s, 3H); 3.50-3.48 (m, 1H); 3.42-3.36 (m, 1H); 3.23 (d, 1H); 3.00-2.81 (m, 2H); 2.50 (dd, 1H); 2.44 (d, 1H); 2.32 (s, 3H); 2.24 (s, 3H); 2.16 (s, 3H); 2.07 (s, 3H); 1.23 (d, 3H).
[0228] 13 C-NMR (75 MHz, CDCl 3 ): δ 171.9, 168.7, 156.2, 147.8, 145.6, 143.3, 141.8, 140.9, 132.7, 131.4, 131.1, 129.4, 129.0, 121.8, 121.4, 115.8, 113.1, 111.9, 111.8, 110.4, 110.0, 103.7, 103.4, 102.0, 81.9, 63.4, 61.8, 60.6, 58.0, 56.2, 55.2, 46.6, 42.3, 41.5, 41.0, 32.1, 29.5, 23.9, 22.9, 21.9, 20.7, 16.1, 14.3, 9.9.
[0229] ESI-MS m/z: Calcd. for C 41 H 43 FN 4 O 9 S: 786.2 Found (M-H 2 O+H + ): 769.3.
[0230] Compound 43 (first isomer): 1 H-NMR (300 MHz, CDCl 3 ): δ 7.85 (s, 1H); 7.33 (d, 1H); 7.23 (d, 1H); 7.07 (t, 1H); 6.99 (t, 1H); 6.63 (s, 1H); 6.22 (d, 1H); 6.00 (d, 1H); 5.70 (s, 1H); 5.20 (d, 1H); 4.86 (s, 1H); 4.52 (d, 1H); 4.48 (s, 1H); 4.16 (d, 1H); 3.80 (s, 3H); 3.53 (d, 1H); 3.22 (d, 1H); 3.01-2.73 (m, 3H); 2.62-2.48 (m, 2H); 2.39-2.17 (m, 1H); 2.31 (s,3H); 2.27 (s, 3H); 2.14 (s, 3H); 2.02 (s, 3H); 1.14 (d, 3H).
[0231] 13 C-NMR (75 MHz, CDCl 3 ): δ 170.6, 168.8, 147.6, 145.7, 143.0, 141.2, 135.7, 131.8, 131.3, 129.2, 127.0, 122.0, 121.8, 121.7, 119.3, 118.5, 115.6, 111.0, 110.2, 102.0, 81.8, 64.0, 61.9, 60.5, 58.1, 58.0, 56.1, 55.3, 44.0, 42.4, 41.5, 38.1, 32.1, 29.5, 24.0, 22.9, 21.8, 20.7, 16.2, 14.3, 9.9.
[0232] ESI-MS m/z: Calcd. for C 41 H 44 N 4 O 9 S: 768.2 Found (M-H 2 O+H + ): 751.3.
[0233] Compound 44 (second isomer): 1 H-NMR (300 MHz, CDCl 3 ): δ 7.62 (s, 1H); 7.36 (d, 1H); 7.27 (d, 1H); 7.09 (t, 1H); 7.00 (t, 1H); 6.59 (s, 1H); 6.21 (d, 1H); 5.98 (d, 1H); 5.71 (s, 1H); 5.15 (d, 1H); 4.84 (s, 1H); 4.51 (d, 2H); 4.17-4.16 (m, 1H); 4.05 (dd, 1H); 3.80 (s, 3H); 3.49-3.48 (m, 1H); 3.42-3.38 (m, 1H); 3.24-3.22 (m, 1H); 3.03-2.81 (m, 2H); 2.57 (dd, 1H); 2.46 (d, 1H); 2.32 (s, 3H); 2.24 (s, 3H); 2.17-2.12 (m, 1H); 2.16 (s, 3H); 2.07 (s, 3H); 1.23 (d, 3H).
[0234] ESI-MS m/z: Calcd. for C 41 H 44 N 4 O 9 S: 768.2 Found (M-H20+H + ): 751.3.
[0235] Compound 45: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.69 (s, 1H); 7.38 (d, 1H); 7.24 (d, 1H); 7.09 (ddd, 1H); 7.03 (s, 1H); 7.00 (ddd, 1H); 6.22 (d, 1H); 6.00 (d, 1H); 5.20 (d, 1H); 4.83 (s, 1H); 4.50 (s, 1H); 4.38 (s, 1H); 4.33 (s, 1H); 4.12 (dd, 1H); 3.77 (s, 3H); 3.68-3.66 (m, 1H); 3.51-3.49 (m, 1H); 3.24-2.85 (m, 4H); 2.70-2.49 (m, 2H); 2.62 (t, 2H); 2.37 (s, 3H); 2.28 (s, 3H); 2.15 (s, 3H); 2.06 (s, 3H); 1.94-1.83 (m, 2H); 1.10 (t, 3H).
[0236] ESI-MS m/z: Calcd. for C 44 H 48 N 4 O 10 S: 824.3 Found (M-H 2 O+H + ): 807.2.
[0237] Compound 46: 1 H-NMR (300 MHz, CDCl 3 ): δ 0.67 (s, 1H); 7.38 (d, 1H); 7.24 (d, 1H); 7.09 (ddd, 1H); 7.00 (ddd, 1H); 7.00 (s, 1H); 6.21 (d, 1H); 6.00 (d, 1H); 5.20 (d, 1H); 4.83 (s, 1H); 4.51 (d, 1H); 4.39 (s, 1H); 4.15 (d, 1H); 3.81 (s, 3H); 3.52 (d, 1H); 3.26 (d, 1H); 3.19-3.11 (m, 1H); 3.06-2.81 (m, 3H); 2.72-2.44 (m, 3H); 2.36 ( s, 3H); 2.31 (s, 3H); 2.17 (s, 3H); 2.03 (s, 3H); 1.54 (s, 9H).
[0238] 13 C-NMR (75 MHz, CDCl 3 ): δ 171.5, 169.2, 151.4, 148.2, 145.7, 144.4, 141.3, 140.9, 135.7, 131.4, 131.1, 130.9, 127.4, 127.1, 124.4, 122.1, 121.5, 119.4, 118.7, 115.6, 111.1, 102.0, 83.3, 81.8, 62.8, 61.9, 60.2, 57.8, 56.3, 56.1, 42.3, 41.5, 39.8, 39.4, 29.9, 27.8, 23.6, 21.7, 20.5, 16.0, 14.3, 9.9.
[0239] ESI-MS m/z: Calcd. for C 45 H 50 N 4 O 11 S: 854.3 Found (M-H 2 O+H + ): 837.2.
[0240] Compound 47: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.68 (s, 1H); 7.38 (d, 1H); 7.24 (d, 1H); 7.19 (dd, 1H); 7.10 (ddd, 1H); 7.06 (s, 1H); 7.00 (ddd, 1H); 6.21 (d, 1H); 6.01 (d, 1H); 5.20 (d, 1H); 5.00 (dd, 1H); 4.83 (s, 1H); 4.70 (dd, 1H); 4.51 (s, 1H); 4.40 (d, 1H); 4.15 (dd, 1H); 3.83 (dd, 1H); 3.82 (s, 3H); 3.53 (d, 1H); 3.28-3.03 (m, 3H); 2.94-2.83 (m, 2H); 2.72-2.46 (m, 3H); 2.38 (s, 3H); 2.33 (s, 3H); 2.17 (s, 3H); 2.07 (s, 3H).
[0241] 13 C-NMR (75 MHz, CDCl 3 ): δ 171.5, 169.0, 150.8, 148.0,. 145.8, 144.0, 143.1, 141.3, 140.9, 135.7, 130.8, 128.2, 127.1, 122.2, 120.0, 119.5, 118.7, 115.5, 113.3, 111.1, 110.5, 102.1, 98.7, 81.9, 62.8, 62.0, 60.5, 57.7, 56.2,.56.0, 42.3, 41.8, 39.9, 39.5, 32.1, 29.5, 23.7, 21.8, 20.5, 16.0, 14.3, 9.9.
[0242] ESI-MS m/z: Calcd. for C 43 H 44 N 4 O 11 S: 824.2 Found (M-H 2 O+H + ): 807.2.
[0243] Compound 48: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.70 (s, 1H); 7.37 (d, 1H); 7.24 (d, 1H); 7.08 (ddd, 1H); 7.00 (ddd, 1H); 6.87 (s, 1H); 6.20 (d, 1H); 6.17-6.05 (m, 1H); 5.99 (d, 1H); 5.47 (dd, 1H); 5.25 (dd, 1H); 5.21 (d, 1H); 4.82 (s, 1H); 4.81 (dd, 1H); 4.50 (d, 1H); 4.44 (s, 1H); 4.36 (dd, 1H); 4.13 (dd, 1H); 4.11 (s, 1H); 3.84 (s, 3H); 3.51 (d, 1H); 3.24-3.00 (m, 3H); 2.89-2.80 (m, 2H); 2.73-2.48 (m, 3H); 2.33 ( s, 3H); 2.31-2.26 (m, 1H); 2.23 (s, 3H); 2.19 (s, 3H); 2.05 (s, 3H).
[0244] 13 C-NMR (75 MHz, CDCl 3 ): δ 171.3, 168.6, 150.5, 148.6, 145.3, 140.9, 140.6, 135.5, 134.6, 131.0, 130.7, 126.7, 124.7, 121.7, 121.3, 119.0, 118.3, 116.2, 118.4, 110.8, 109.9, 101.7, 81.6, 72.6, 62.4, 61.6, 59.3, 57.6, 57.5, 55.9, 55.1, 42.0, 41.3, 39.4, 39.0, 29.2, 23.5, 22.5, 21.4, 20.3, 15.7, 14.0, 9.
[0245] ESI-MS m/z: Calcd. for C 43 H 46 N 4 O 9 S: 794.3 Found (M-H 2 O+H + ): 777.2.
[0246] Compound 49: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.60 (s, 1H); 7.42-7.39 (m, 2H); 7.09-7.00 (m, 2H); 6.81 (s, 1H); 6.16-6.04 (m, 2H); 6.07 (s, 1H); 5.99 (s, 1H); 5.52-5.43 (m, 2H); 5.24 (d, 1H); 5.11 (d, 1H); 4.96 (d, 1H); 4.80-4.32 (m, 6H); 4.13-4.10 (m, 2H); 3.81 (s, 3H); 3.58-3.56 (m, 1H); 3.46-3.40 (m, 1H); 3.24-3.20 (m, 1H); 2.99-2.87 (m, 2H); 2.67-2.53 (m, 2H); 2.31 (s, 3H); 2.23 (s; 3H); 2.19 (s, 3H); 2.02 (s, 3H).
[0247] ESI-MS m/z: Calcd. for C 46 H 50 N 4 O 9 S: 834.3 Found (M-H 2 O+H + ): 817.2.
[0248] To a solution of ET-736-CN in THF/H 2 O 3:1 (0.027M) were added 15 equiv. of KOH. The reaction mixture was stirred at room temperature for 5 h. After this time the reaction was quenched with an aqueous saturated solution of NaCl, extracted with CH 2 Cl 2 . The organic layer was dried over Na 2 SO 4 . Chromatography gives pure compound 50.
[0249] 1 H-NMR (300 MHz, CDCl 3 ): δ 7.59 (s, 1H); 7.40 (d, 1H); 7.25 (d, 1H); 7.11 (ddd, 1H); 7.02 (ddd, 1H); 6.67 (s, 1H); 6.16 (d, 1H); 5.93 (d, 1H); 5.90 (s, 1H); 5.62 (s, 1H); 5.06 (d, 1H); 4.46 (d, 1H); 4.36 (s, 1H); 4.31 (dd, 1H); 4.19 (d, 1H); 4.12 (dd, 1H); 3.82 (s, 3H); 3.55 (d, 1H); 3.42 (d, 1H); 3.20-2.80 (m, 4H); 2.69-2.53 (m, 3H); 2.38 (s,. 3H); 2.21 (s, 3H); 2.18 (s, 3H).
[0250] ESI-MS m/z: Calcd. for C 39 H 39 N 5 O 7 S: 721.3 Found (M+H + ): 722.2.
[0000] Derivatives of Et-694:
[0251] Method 5: To a solution of 1 equiv. of ET-694-CN, compound 50 in CH 2 Cl 2 (0.032M) under argon at room temperature were added 2 equiv. of pyridine and 2 equiv. of acid chloride, chlorofomiate or anhydride. The reaction was followed by TLC and quenched with an aqueous saturated solution of NaHCO 3 , extracted with CH 2 Cl 2 and the organic layers dried over Na 2 SO 4 . Flash chromatography gives pure compounds.
[0252] Compound 51: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.65 (s, 1H); 7.40 (d, 1H); 7.26 (d, 1H); 7.12 (s, 1H); 7.11 (ddd, 1H); 7.04 (ddd, 1H); 6.30 (d, 1H); 6.19 (d, 1H); 5.10 (d, 1H); 4.40-4-30 (m, 2H); 4.23-4.16 (m, 1H); 3.76 (s, 3H); 3.50-3.44 (m, 2H); 3.19-3.13 (m, 2H); 3.03-2.83 (m, 2H); 2.66-2.47 (m, 3H); 2.40 (s, 3H); 3.36-2.22 (m, 2H); 2.16 (s, 3H); 2.07 (s, 3H).
[0253] ESI-MS m/z: Calcd. for C 43 H 38 F 7 N 5 O 8 S: 917.2 Found (M+H + ): 918.1.
[0254] Compound 52: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.72 (d, 1H), 7.38 (d, 1H), 7.26 (d, 1H), 7.10 (t, 1H). 7.00 (t, 1H), 6.65 (s, 1H), 6.24 (d, 1H), 6.02 (d, 1H), 5.74 (s, 1H), 5.08 (d, 1H), 4.54 (broad s, 1H), 4.33 (s, 1H), 4.27 (d, 1H), 4.21 (s, 1H), 4.20 (d, 1H), 3.80 (s, 3H), 3.43 (m, 2H), 3.20-2.81 (m, 4H), 2.64-2.58 (m, 3H), 2.53 (t, 2H), 2.37 (s, 3H), 2.26 (m, 1H), 2.21 (s, 3H), 2.05 (s, 3H), 1.74 (sext, 2H), 1.01 (t, 3H).
[0255] ESI-MS m/z: Calcd. for C 43 H 45 N 5 O 8 S: 791.3 Found (M+H + ): 792.2.
[0256] Compound 53: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.71 (s, 1H), 7.39 (d, 1H), 7.26 (d, 1H), 7.11 (t, 1H), 7.02 (t, 1H), 6.66 (s, 1H), 6.26 (s, 1H), 6.04 (s, 1H), 5.80 (s, 1H), 5.09 (d, 1H), 4.52 (broad s, 1H), 4.34 (s, 1H), 4.27 (d, 1H), 4.22 (d, 1H), 4.20 (m, 1H), 3.82 (s, 3H), 3.79 (m, 2H), 3.42 (m, 2H), 3.16 (m, 1H), 3.07-2.81 (m, 5H), 2.64-2.50 (m, 3H), 2.37 (s, 3H), 2.25 (m, 1H), 2.21 (s, 3H), 2.08 (s, 3H).
[0257] ESI-MS m/z: Calcd. for C 42 H 42 ClN 5 O 8 S: 811.2 Found (M+H + ): 812.2.
[0258] Compound 54: This product was obtained with 4 equiv. of cinnamoyl chloride and 4 equiv. of pyridine.
[0259] 1 H-NMR (300 MHz, CDCl 3 ): δ 7.83 (d, 1H), 7.75 (s, 1H), 7.58 (m, 2H), 7.46 (m, 3H), 7.39 (d, 1H), 7.27 (d, 1H), 7.11 (t, 1H), 7.02 (t, 1H), 6.61 (s, 1H) 6.58 (d, 1H), 6.26 (s, 1H), 6.05 (s, 1H), 5.52 (s, 1H), 5.09 (d, 1H), 4.60 (broad s, 1H), 4.37 (s, 1H), 4.27 (d, 1H), 4.25 (s, 1H), 4.23 (m, 1H), 3.47 (s, 3H), 3.45 (m, 2H), 3.15 (m, 1H), 3.04 (d, 1H), 2.96 (m, 1H), 2.84 (m, 1H), 2.70-2.53 (m, 3H), 2.33 (m, 1H), 2.29 (s, 3H), 2.21 (s, 3H), 2.12 (s, 3H).
[0260] ESI-MS m/z: Calcd. for C 48 H 45 N 5 O 8 S: 851.3 Found (M+H + ): 852.2.
[0261] Compound 55: This product was obtained with 6 equiv. of allylchloroformiate and 6 equiv. of pyridine.
[0262] 1 H-NMR (300 MHz, CDCl 3 ): δ 7.74 (s, 1H), 7.39 (d, 1H), 7.25 (d, 1H), 7.10 (t, 1H), 7.01 (t, 1H), 6.65 (s, 1H), 6.25 (s, 1H), 6.03 (s, 1H), 5.90 (ddd, 1H), 5.78 (s, 1H), 5.37 (d, 1H), 5.24 (d, 1H), 5.08 (d, 1H), 4.61 (m, 3H), 4.32 (s, 1H), 4.28 (d, 1H), 4.22 (s, 1H), 4.20 (d, 1H), 3.80 (s, 3H), 3.42 (m, 2H), 3.18 (m, 1H), 3.09-2.81 (m, 3H), 2.59 (m, 3H), 2.37 (s, 3H), 2.26 (m, 1H), 2.21 (s, 3H), 2.12 (s, 3H).
[0263] ESI-MS m/z: Calcd. for C 43 H 43 N 5 O 9 S: 805.3 Found (M+H + ): 806.3
[0264] Compound 56: This product was obtained with 3 equiv. of trifluoroacetic anhydride and 3 equiv. of pyridine
[0265] 1 H-NMR (300 MHz, CDCl 3 ): δ 7.66 (s, 1H), 7.40 (d, 1H), 7.26 (d, 1H), 7.11 (t, 1H), 7.02 (t, 1H), 6.65 (s, 1H), 6.31 (d, 1H), 6.08 (d, 1H), 5.74 (s, 1H), 5.11 (d, 1H), 4.55. (s, 1H), 4.36 (s, 1H), 4.28 (d, 1H), 4.25 (s, 1H), 4.23 (d, 1H), 3.79 (s, 3H), 3.46 (m, 2H), 3.15 (m, 1H), 3.09-2.46 (m, 6H), 2.36 (s, 3H), 2.23 (s, 3H), 2.20 (m, 1H), 2.01 (s, 3H).
[0266] ESI-MS m/z: Calcd. for C 41 H 38 F 3 N 5 O 8 S: 817.2 Found (M+H + ): 818.2
[0267] Compound 57: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.74 (s, 1H), 7.40 (d, 1H), 7.27 (d, 1H), 7.11 (t, 1H), 7.02 (t, 1H), 6.65 (s, 1H), 6.23 (s, 1H), 6.02 (s, 1H), 5.74 (s,. 1H), 5.09 (d, 1H), 4.66 (s, 1H), 4.32-4.21 (m, 4H), 3.81 (s, 3H), 3.40 (m, 2H), 3.21-2.86 (m, 3H), 2.80 (m, 1H), 2.64 (m, 3H), 2.37 (s, 3H), 2.29 (m, 1H), 2.21 (s, 3H), 2.11 (s, 3H), 1.45 (s, 9H).
[0268] ESI-MS m/z: Calcd. for C 44 H 47 N 5 O 9 S: 821.3 Found (M+H + ): 822.0.
[0269] Compound 58: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.72 (s, 1H), 7.39 (d, 1H), 7.26 (d, 1H); 7.11 (t, 1H), 7.02 (t, 1H), 6.99 (s, 1H), 6.24 (s, 1H), 6.03 (s, 1H), 5.09 (d, 1H), 4.61 (s, 1H), 4.30 (s, 1H), 4.20 (m, 2H), 3.98 (s, 1H), 3.83 (s, 3H), 3.45 (m, 2H), 3.21-2.90 (m, 3H), 2.80 (m, 1H), 2.59 (s, 3H), 2.36 (s, 3H), 2.31 (m, 1H), 2.20 (s, 3H), 2.12 (s, 3H), 1.54 (s, 9H), 1.45 (s, 9H).
[0270] ESI-MS m/z: Calcd. for C 49 H 55 N 5 O 11 S: 921.4 Found (M+H + ): 922.3.
[0271] The monoBoc derivative in C-5 was obtained with 6 equiv. of Boc anhydride and 6 equiv of pyridine. With these conditions traces of diBoc derivative in C-5 and C-18 was isolated as a secondary product. This last compound can be obtained as the major product when the reaction was performed with TEA as base.
[0272] Compound 59: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.71 (s, 1H), 7.39 (d, 1H), 7.26 (d, 1H), 7.10 (t, 1H), 7.04 (t, 1H), 6.95 (dd, 1H), 6.65 (s, 1H), 6.26 (s, 1H), 6.04 (s, 1H), 5.78 (s, 1H), 5.09 (d, 1H), 4.99 (dd, 1H), 4.63 (s, 1H), 4.60 (dd, 1H), 4.33 (s, 1H), 4.29 (d, 1H), 4.22 (s, 1H), 4.21 (d, 1H), 3.78 (s, 3H), 3.42 (m, 2H), 3.21-2.79 (m, 4H), 2.63 (m, 3H), 2.37 (s, 3H), 2.27 (m, 1H), 2.22 (s, 3H), 2.13 (s, 3H).
[0273] ESI-MS m/z: Calcd. for C 42 H 41 N 5 O 9 S: 791.3 Found (M+H + ): 792.1
[0274] Compound 60: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.70 (s, 1H), 7.40 (d, 1H), 7.26 (d, 1H), 7.18 Me (dd, 1H), 7.11 (t, 1H), 7.05 (s, 1H), 7.02 (t, 1H), 6.97 (dd, 1H), 6.27 (s, 1H), 6.05 (s, 1H), 5.10 (d, 1H), 5.09-5.00 (m, 1H), 5.05 (s, 1H), 4.72 (dd, 1H), 4.60 (dd, 1H), 4.56 (s, 1H), 4.33 (s, 1H), 4.22 (m, 2H), 3.97 (d, 1H), 3.78 (s, 3H), 3.46 (m, 2H), 3.18 (m, 1H), 3.11 (d, 1H), 2.97 (dd, 1H), 2.85 (m, 1H), 2.71-2.51 (m, 3H), 2.37 (s, 3H), 2.32 (m, 1H), 2.21 (s, 3H), 2.16 (s, 3H).
[0275] ESI-MS m/z: Calcd. for C 45 H 43 N 5 O 11 S: 861.3 Found (M+H + ): 862.7.
[0276] Method 6: To a solution of 1 equiv. of ET-694-CN, compound 50 in CH 2 Cl 2 (0.032M) under argon at room temperature were added 2 equiv. of acid, 2 equiv. of EDC.HCl and 2 equiv. of DMAP. The reaction was followed by TLC and quenched with an aqueous saturated solution of NaHCO 3 , extracted with CH 2 Cl 2 and the organic layers dried over Na 2 SO 4 . Flash chromatography gives pure compounds.
[0277] Compound 61: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.70 (s, 1H), 7.39 (d, 1H), 7.26 (d, 1H), 7.11 (t, 1H), 7.00 (t, 1H), 6.65 (s, 1H), 6.23 (s, 1H), 6.03 (s, 1H), 5.72 (s, 1H), 5.09 (d, 1H), 4.57 (broad s, 1H), 4.33 (s, 1H), 4.26 (d, 1H), 4.21 (s, 1H), 4.19 (d, 1H), 3.80 (s, 3H), 3.44 (m, 2H), 3.16 (m, 1H), 3.03 (d, 1H), 3.00-2.89 (m, 2H), 2.68-2.52 (m, 3H), 2.54 (t, 2H), 2.37 (s, 3H), 2.31 (m, 1H), 2.21 (s, 3H), 2.04 (s, 3H), 1.65 (m, 2H), 1.29 (m, 8H), 0.87 (m, 3H).
[0278] ESI-MS m/z: Calcd. for C 47 H 53 N 5 O 8 S: 847.4 Found (M+H + ): 848.3.
[0279] Method 4.
[0280] To a solution of 1 equiv. of starting material in CH 3 CN/H 2 O 3:2 (0.009M) were added 30 equiv. of AgNO 3 . After 24 h the reaction was quenched with a mixture 1:1 of saturated solutions of brine and NaHCO 3 , stirred for 10 min and diluted and extracted with CH 2 Cl 2 . The organic layer was dried with Na 2 SO 4 . Chromatography gives pure compounds.
[0281] Compound 62: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.65 (s, 1H); 7.40 (d, 1H); 7.25 (d, 1H); 7.10 (ddd, 1H); 7.01 (ddd, 1H); 6.66 (s, 1H); 6.27 (d, 1H); 6.04 (d, 1H); 5.69 (s, 1H); 5.23 (d, 1H); 4.85 (s, 1H); 4.51 (d, 1H); 4.47 (s, 1H); 4.19 (s, 1H); 4.15 (dd, 1H); 3.78 (s, 3H); 3.52-3.50 (m, 1H); 3.26-3.14 (m, 2H); 3.04-2.80 (m, 3H); 2.72-2.47 (m, 3H); 2.36 (s, 3H); 2.20 (s, 3H); 2.05 (s, 3H).
[0282] ESI-MS m/z: Calcd. for C 42 H 39 F 7 N 4 O 9 S: 908.3 Found (M+H + ): 909.2.
[0283] Compound 63: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.71 (d, 1H), 7.38 (d, 1H), 7.26 (d, 1H), 7.09 (t, 1H), 7.03 (t, 1H), 6.67 (s, 1H), 6.21 (d, 1H), 5.99 (d, 1H), 5.71 (broad s, 1H), 5.18 (d, 1H), 4.83 (s, 1H), 4.50 (d, 1H), 4.46 (broad s, 1H), 4.17 (d, 1H), 4.12 (d, 1H), 3.81 (s, 3H), 3.51 (d, 1H), 3.24-3.18 (m, 2H), 3.00 (d, 1H), 2.85 (m, 2H), 2.70-2.50 (m, 5H), 2.37 (s, 3H), 2.27 (m, 1H), 2.19 (s, 3H), 2.04 (s, 3H), 1.74 (sext, 2H), 1.01 (t, 3H).
[0284] ESI-MS m/z: Calcd. for C 42 H 46 N 4 O 9 S: 782.3 Found (M+H + ): 783.2.
[0285] Compound 64: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.71 (s, 1H), 7.39 (d, 1H), 7.25 (d, 1H), 7.10 (t, 1H), 7.01 (t, 1H), 6.66 (s, 1H), 6.22 (s, 1H), 6.00 (s, 1H), 5.90 (ddd, 1H), 5.74 (broad s, 1H), 5.37 (d, 1H), 5.22 (t, 1H), 4.83 (s, 1H), 4.59 (m, 2H), 4.49 (s, 1H), 4.29 (dd, 1H), 4.15 (m, 2H), 3.80 (s, 3H), 3.65 (m, 1H), 3.51 (m, 2H), 3.18 (m, 1H), 3.09-2.81 (m, 3H), 2.59 (m, 3H), 2.37 (s, 3H), 2.26 (m, 1H), 2.21 (s, 3H), 2.12 (s, 3H).
[0286] ESI-MS m/z: Calcd. for C 42 H 44 N 4 O 10 S: 796.3 Found (M+H + ): 797.0
[0287] Compound 65: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.74 (s, 1H), 7.40 (d, 1H), 7.27 (d, 1H), 7.11 (t, 1H), 7.02 (t, 1H), 6.65 (s, 1H), 6.23 (s, 1H), 6.02 (s, 1H), 5.74 (broad s, 1H), 5.20 (d, 1H), 4.82 (s, 1H), 4.58 (s, 1H), 4.49 (m, 1H), 4.13 (m, 2H), 3.81 (s, 3H), 3.49 (m, 1H), 3.21 (m, 2H), 3.02 (d, 1H), 2.80 (m, 3H), 2.64 (m, 2H), 2.37 (s, 3H), 2.29 (m, 1H), 2.21 (s, 3H), 2.11 (s, 3H), 1.45 (s, 9H).
[0288] ESI-MS m/z: Calcd. for C 43 H 48 N 4 O 10 S: 812.3 Found (M+H + ): 813.0.
[0289] Compound 66: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.71 (s, 1H), 7.39 (d, 1H), 7.26 (d, 1H); 7.11 (t, 1H), 7.02 (t, 1H), 6.99 (s, 1H), 6.21 (s, 1H), 6.00 (s, 1H), 5.19 (d, 1H), 4.80 (s, 1H), 4.51 (m, 2H), 4.16 (m, 2H), 3.83 (s, 3H), 3.54 (m, 1H), 3.28-3.04 (m, 3H), 2.92-2.78 (m, 2H), 2.59 (m, 3H), 2.36 (s, 3H), 2.31 (m, 1H), 2.18 (s, 3H), 2.11 (s, 3H), 1.54 (s, 9H), 1.45 (s, 9H).
[0290] ESI-MS m/z: Calcd. for C 48 H 56 N 4 O 12 S: 912.4 Found (M+H + ): 913.1.
[0291] Compound 67: 1 H-NMR (300 MHz, CDCl 3 ): δ 7.70 (s, 1H), 7.39 (d, 1H), 7.26 (d, 1H), 7.10 (t, 1H), 7.01 (t, 1H), 6.95 (dd, 1H), 6.66 (s, 1H), 6.24 (s, 1H), 6.01 (s, 1H), 5.75 (s, 1H), 5.21 (d, 1H), 4.99 (dd, 1H), 4.84 (s, 1H), 4.58 (dd, 1H), 4.55 (s, 1H), 4.51 (s, 1H), 4.20 (s, 1H), 4.15 (d, 1H), 3.78 (s, 3H), 3.49 (m, 1H), 3.21 (m, 2H), 3.00 (d, 1H), 2.86 (m, 2H), 2.59 (m, 3H), 2.37 (s, 3H), 2.27 (m, 1H), 2.20 (s, 3H), 2.12 (s, 3H).
[0292] ESI-MS m/z: Calcd. for C 41 H 42 N 4 O 10 S: 782.3 Found (M+H + ): 783.1
[0293] Compound 68: 1 H-NMR (300 MHz, CDCl 3 ): 7.67 (s, 1H), 7.39 (d, 1H), 7.24 (d, 1H), 7.17 (dd, 1H), 7.10 (t, 1H), 7.05 (s, 1H), 7.02 (t, 1H), 6.97 (dd, 1H), 6.24 (s, 1H), 6.02 (s, 1H), 5.21 (d, 1H), 5.06 (dd, 1H), 5.01 (dd, 1H), 4.83(s, 1H); 4.72 (dd, 1H), 4.60 (dd, 1H), 4.51 (s, 1H), 4.48 (s, 1H), 4.15 (dd, 1H), 3.86(d, 1H), 3.78 (s, 3H), 3.54 (d, 1H), 3.28-3.18 (m, 2H), 3.07 (d, 1H), 2.94-2.84(m, 2H), 2.67-2.52 (m, 3H), 2.37 (s, 3H), 2.32 (m, 1H), 2.18 (s, 3H), 2.14 (s, 3H).
[0294] ESI-MS m/z: Calcd. for C 44 H 44 N 4 O 12 S: 852.3 Found (M+H + ): 853.5
Bioassays for Antitumor Screening
[0295] The finality of these assays is to interrupt the growth of a “in vitro” tumor cell culture by means of a continued exhibition of the cells to the sample to be testing.
[0296] Cell Lines
Name N° ATCC Species Tissue Characteristics P-388 CCL-46 mouse ascites fluid lymphoid neoplasm K-562 CCL-243 human leukemia erythroleukemia (pleural effusion) A-549 CCL-185 human lung lung carcinoma “NSCL” SK-MEL-28 HTB-72 human melanoma malignant melanoma HT-29 HTB-38 human colon colon adenocarcinoma LoVo CCL-229 human colon colon adenocarcinoma LoVo-Dox human colon colon adenocarcinoma (MDR) SW620 CCL-228 human colon colon adenocarcinoma (lymph node metastasis) DU-145 HTB-81 human prostate prostate carcinoma, not androgen receptors LNCaP CRL-1740 human prostate prostate adenocarci- noma, with androgen receptors SK-BR-3 HTB-30 human breast breast adenocarci- noma, Her2/neu+, (pleural effusion) MCF-7 HTB-22 human breast breast adenocarci- noma, (pleural effusion) MDA-MB- HTB-26 human breast breast adenocarci- 231 noma, Her2/neu+, (pleural effusion) IGROV-1 human ovary ovary adenocarcinoma IGROV-ET human ovary ovary adenocarcinoma, characterized as ET- 743 resistant cells SK-OV-3 HTB-77 human ovary ovary adenocarcinoma (malignant ascites) OVCAR-3 HTB-161 human ovary ovary adenocarcinoma HeLa CCL-2 human cervix cervix epitheloid carcinoma HeLa-APL CCL-3 human cervix cervix epitheloid carcinoma, character- ized as aplidine resistant cells A-498 HTB-44 human kidney kidney carcinoma PANC-1 CRL-1469 human pancreas pancreatic epitheloid carcinoma HMEC1 human endothelium
Inhibition of Cells Growth by Colorimetric Assay
[0297] A colorimetric type of assay, using sulphorhodamine B (SRB) reaction has been adapted for a quantitative measurement of cell growth and viability [following the technique described by Philip Skehan, et al. (1990), New colorimetric cytotoxicity assay for anticancer drug screening, J. Natl. Cancer Inst., 82:1107-1112]
[0298] This form of the assay employs 96 well cell culture microplates of 9 mm diameter (Faircloth, 1988; Mosmann, 1983). Most of the cell lines are obtained from American Type Culture Collection (ATCC) derived from different human cancer types.
[0299] Cells are maintained in RPMI 1640 10% FBS, supplemented with 0.1 g/l penicillin and 0.1 g/l streptomycin sulphate and then incubated at 37° C., 5% CO 2 and 98% humidity. For the experiments, cells were harvested from subconfluent cultures using trypsin and resuspended in fresh medium before plating.
[0300] Cells are seeded in 96 well microtiter plates, at 5×10 3 cells per well in aliquots of 195 μl medium, and they are allowed to attach to the plate surface by growing in drug free medium for 18 hours. Afterward, samples are added in aliquots of 5 μl in a ranging from 10 to 10 −8 μg/ml, dissolved in DMSO/EtOH/PBS (0.5:0.5:99). After 48 hours exposure, the antitumor effect are measured by the SRB methodology: cells are fixed by adding 50 μl of cold 50% (wt/vol) trichloroacetic acid (TCA) and incubating for 60 minutes at 4° C. Plates are washed with deionized water and dried. One hundred μl of SRB solution (0.4% wt/vol in 1% acetic acid) is added to each microtiter well and incubated for 10 minutes at room temperature. Unbound SRB is removed by washing with 1% acetic acid. Plates are air dried and bound stain is solubilized with Tris buffer. Optical densities are read on a automated spectrophotometric plate reader at a single wavelength of 490 nm.
[0301] The values for mean +/− SD of data from triplicate wells are calculated. Some parameters for cellular responses can be calculated: GI=growth inhibition, TGI=total growth inhibition (cytostatic effect) and LC=cell killing (cytotoxic effect).
[0302] Obtained results may predict the usefulness of a certain drug as a potential cancer treatment. For this technique, compounds which show GI 50 values smaller than 10 μg/ml are selected to continue with further studies. GI 50 d ata allow to predict that not only could a drug be cystostatic, but also it could have a potential in terms of tumor reduction.
[0303] Activity Data (Molar).
Compound 1 A549 IC 50 1.31E − 09 HT29 1.31E − 09
[0304]
Compound 2
Compound 3
Compound 4
Compound 5
Compound 6
Compound 7
A549
GI 50
6.30E − 10
3.45E − 07
2.30E − 06
1.29E − 08
5.13E − 09
7.67E − 07
TGI
6.30E − 09
3.45E − 06
6.90E − 06
1.29E − 07
5.13E − 08
1.28E − 07
LC 50
6.30E − 05
5.75E − 05
1.15E − 05
1.29E − 05
1.28E − 05
1.28E − 06
HT29
GI 50
1.26E − 09
2.30E − 07
2.30E − 06
1.29E − 08
5.13E − 09
6.39E − 08
TGI
1.26E − 09
2.30E − 07
2.30E − 06
1.29E − 08
5.13E − 09
6.39E − 08
LC 50
6.30E − 05
5.75E − 05
1.15E − 05
5.14E − 06
5.13E − 06
1.28E − 06
H-MEC-1
GI 50
TGI
LC 50
[0305]
Compound 8
Compound 9
Compound 10
Compound 11
Compound 12
Compound 13
A549
GI 50
2.52E − 09
2.52E − 08
3.91E − 08
1.89E − 08
7.28E − 09
6.31E − 09
TGI
1.01E − 08
1.01E − 07
1.28E − 07
5.00E − 08
8.35E − 08
6.79E − 08
LC 50
1.26E − 05
8.82E − 06
1.28E − 05
1.29E − 07
1.26E − 05
1.26E − 05
HT29
GI 50
2.52E − 09
3.78E − 07
4.03E − 08
3.09E − 08
1.37E − 08
3.33E − 07
TGI
2.52E − 09
3.78E − 07
1.28E − 05
1.29E − 07
1.26E − 07
1.26E − 06
LC 50
5.04E − 06
1.26E − 05
1.28E − 05
1.29E − 05
1.26E − 05
1.26E − 05
H-MEC-1
GI 50
TGI
LC 50
[0306]
Compound 15
Compound 16
Compound 17
Compound 18
Compound 19
Compound 20
A549
GI 50
4.78E − 09
3.67E − 08
5.39E − 09
6.77E − 09
3.27E − 09
3.30E − 07
TGI
1.31E − 08
1.28E − 07
4.41E − 08
1.29E − 07
1.29E − 08
1.20E − 06
LC 50
1.27E − 06
4.44E − 06
6.67E − 06
1.29E − 05
1.29E − 05
6.77E − 06
HT29
GI 50
4.16E − 09
4.28E − 08
2.22E − 08
5.62E − 09
4.45E − 09
5.96E − 07
TGI
1.31E − 08
1.28E − 07
1.28E − 08
1.29E − 07
1.29E − 07
1.20E − 05
LC 50
1.31E − 05
1.28E − 05
1.28E − 05
1.29E − 05
1.29E − 05
1.20E − 05
H-MEC-1
GI 50
TGI
LC 50
[0307]
Compound 21
Compound 22
Compound 23
Compound 24
Compound 25
Compound 50
A549
GI 50
7.58E − 07
3.93E − 08
1.18E − 07
1.24E − 05
1.18E − 05
4.16E − 07
TGI
6.99E − 06
1.20E − 07
1.26E − 06
1.24E − 05
1.18E − 05
6.93E − 07
LC 50
1.16E − 05
1.20E − 05
1.11E − 05
1.24E − 05
1.18E − 05
1.39E − 06
HT29
GI 50
1.18E − 06
1.20E − 07
2.47E − 07
1.24E − 05
1.18E − 05
6.93E − 07
TGI
1.16E − 05
5.70E − 06
1.11E − 05
1.24E − 05
1.18E − 05
6.93E − 07
LC 50
1.16E − 05
1.20E − 05
1.11E − 05
1.24E − 05
1.18E − 05
6.93E − 06
H-MEC-1
GI 50
TGI
LC 50
[0308]
Compound 52
Compound 53
Compound 54
Compound 55
Compound 56
Compound 58
A549
GI 50
4.70E − 08
2.61E − 07
1.10E − 07
4.95E − 08
9.30E − 09
8.91E − 08
TGI
1.26E − 07
7.84E − 07
3.53E − 07
3.11E − 07
2.36E − 07
1.34E − 06
LC 50
9.43E − 04
1.22E − 05
1.10E − 06
1.10E − 05
3.79E − 06
1.08E − 05
HT29
GI 50
7.93E − 08
3.09E − 07
1.30E − 07
8.20E − 08
4.74E − 08
2.30E − 07
TGI
1.26E − 05
1.23E − 06
5.41E − 07
1.24E − 06
1.22E − 05
1.08E − 05
LC 50
1.26E − 05
1.23E − 05
3.37E − 06
1.24E − 05
1.22E − 05
1.08E − 05
H-MEC-1
GI 50
3.47E − 07
1.32E − 07
5.48E − 10
4.17E − 09
1.02E − 08
TGI
6.95E − 09
1.23E − 05
1.13E − 09
9.65E − 09
1.08E − 05
LC 50
1.26E − 08
1.23E − 05
6.68E − 09
3.78E − 07
1.08E − 05
[0309]
Compound 59
Compound 61
Compound 63
Compound 64
Compound 65
Compound 66
A549
GI 50
2.66E − 09
1.18E − 05
3.12E − 09
1.64E − 09
2.05E − 09
2.09E − 08
TGI
2.26E − 06
1.18E − 05
9.53E − 09
6.83E − 09
6.30E − 09
5.75E − 08
LC 50
4.98E − 06
1.18E − 05
3.03E − 06
1.10E − 07
4.79E − 08
3.76E − 07
HT29
GI 50
3.80E − 09
1.18E − 05
3.88E − 09
1.91E − 09
8.56E − 10
2.80E − 08
TGI
1.84E − 08
1.18E − 05
1.28E − 08
1.25E − 08
2.05E − 08
1.13E − 07
LC 50
1.26E − 05
1.18E − 05
1.28E − 05
1.25E − 05
1.23E − 05
1.10E − 05
H-MEC-1
GI 50
4.00E − 09
3.94E − 07
2.72E − 09
3.10E − 10
6.13E − 10
2.07E − 08
TGI
1.26E − 08
8.05E − 07
1.28E − 08
1.25E − 08
4.35E − 08
8.04E − 08
1,
1
LC 50
1.26E − 05
3.40E − 06
1.28E − 05
1.25E − 05
1.23E − 05
1.10E − 05
[0310]
Compound 67
A549
GI 50
4.55E − 10
TGI
2.86E − 09
LC 50
1.28E − 07
HT29
GI 50
1.90E − 09
TGI
1.28E − 07
LC 50
1.28E − 05
H-MEC-1
GI 50
5.21E − 10
TGI
1.28E − 07
LC 50
1.28E − 05
[0311]
Compound 14
Compound 26
Compound 27
Compound 28
Compound 29
Compound 30
A549
GI 50
2.64E − 07
2.65E − 09
2.55E − 10
3.48E − 09
2.32E − 08
3.90E − 11
TGI
8.25E − 07
3.97E − 09
8.92E − 10
4.65E − 08
3.48E − 08
2.60E − 10
LC 50
6.86E − 06
1.32E − 08
6.37E − 09
3.48E − 08
9.29E − 08
1.04E − 09
HT29
GI 50
4.18E − 07
3.97E − 09
2.55E − 10
1.16E − 08
2.32E − 08
1.04E − 10
TGI
1.59E − 06
7.95E − 09
7.64E − 10
6.97E − 08
6.97E − 08
3.90E − 10
LC 50
1.29E − 05
1.32E − 08
1.15E − 09
1.05E − 07
1.05E − 07
1.04E − 09
SW-620
GI 50
2.65E − 09
2.55E − 10
6.97E − 09
2.32E − 08
2.60E − 11
TGI
7.95E − 09
6.37E − 10
2.32E − 08
6.97E − 08
3.90E − 10
LC 50
7.95E − 08
1.15E − 09
9.29E − 08
1.05E − 07
1.30E − 09
MEL-28
GI 50
1.98E − 07
2.65E − 09
2.55E − 10
2.32E − 08
2.32E − 08
2.60E − 11
TGI
5.19E − 07
5.30E − 09
6.37E − 10
3.48E − 08
3.48E − 08
1.30E − 10
LC 50
2.37E − 06
1.06E − 08
1.27E − 09
8.13E − 08
8.13E − 08
6.50E − 10
OVCAR
GI 50
TGI
LC 50
A498
GI 50
2.65E − 09
2.55E − 10
3.48E − 09
3.48E − 09
1.30E − 10
TGI
6.62E − 09
5.10E − 10
1.16E − 08
1.16E − 08
5.20E − 10
LC 50
2.65E − 08
1.27E − 09
5.81E − 08
1.16E − 07
2.60E − 09
DU145
GI 50
9.46E − 08
2.65E − 09
2.55E − 11
2.32E − 09
2.32E − 08
1.30E − 11
TGI
1.39E − 06
3.97E − 09
8.92E − 11
3.48E − 09
3.48E − 08
3.90E − 11
LC 50
1.29E − 05
1.06E − 08
3.82E − 09
9.29E − 09
9.29E − 08
1.30E − 10
MCF
GI 50
2.65E − 09
2.55E − 10
5.81E − 09
2.32E − 08
2.60E − 10
TGI
5.30E − 09
1.27E − 09
2.32E − 08
3.48E − 08
3.90E − 10
LC 50
1.19E − 08
1.15E − 08
1.16E − 07
1.16E − 07
2.60E − 09
MB231
GI 50
2.65E − 09
2.55E − 10
3.48E − 09
2.32E − 08
2.60E − 12
TGI
5.30E − 09
6.37E − 09
9.29E − 09
4.65E − 08
1.30E − 10
LC 50
1.32E − 08
1.27E − 08
1.16E − 07
1.16E − 07
3.90E − 09
H-MEC-1
GI 50
TGI
LC 50
LNCAP
GI 50
6.12E − 08
TGI
1.77E − 07
LC 50
5.35E − 07
SK-OV3
GI 50
TGI
LC 50
IGROV
GI 50
2.26E − 07
TGI
7.44E − 07
LC 50
5.14E − 06
IGROV-ET
GI 50
5.69E − 07
TGI
1.30E − 06
LC 50
1.29E − 05
SK-BR3
GI 50
2.17E − 07
TGI
5.37E − 07
LC 50
1.62E − 06
K562
GI 50
4.47E − 08
TGI
1.74E − 07
LC 50
1.29E − 06
PANC-1
GI 50
2.76E − 07
TGI
8.25E − 07
LC 50
1.29E − 05
LOVO
GI 50
1.41E − 07
TGI
3.93E − 07
LC 50
1.10E − 06
LOVO-DOX
GI 50
5.84E − 07
TGI
3.84E − 06
LC 50
1.29E − 05
HELA
GI 50
1.14E − 07
TGI
3.10E − 07
LC 50
8.10E − 07
HELA-APL
GI 50
2.43E − 07
TGI
4.88E − 07
LC 50
9.80E − 07
[0312]
Compound 31
Compound 32
Compound 33
Compound 34
Compound 35
Compound 36
A549
GI 50
2.59E − 09
3.88E − 09
3.82E − 10
5.10E − 09
3.03E − 09
2.84E − 08
TGI
5.19E − 09
2.59E − 08
1.27E − 09
2.55E − 08
7.65E − 09
5.07E − 08
LC 50
3.89E − 08
9.06E − 08
5.10E − 09
8.92E − 08
4.09E − 06
9.09E − 08
HT29
GI 50
3.89E − 09
7.76E − 09
2.55E − 10
7.64E − 09
4.19E − 09
6.18E − 08
TGI
7.78E − 09
2.59E − 08
7.64E − 10
2.54E − 09
1.32E − 08
1.87E − 07
LC 50
1.30E − 08
1.03E − 07
1.15E − 09
1.15E − 08
1.29E − 05
1.30E − 05
SW-620
GI 50
2.59E − 09
5.17E − 09
2.55E − 10
1.02E − 08
TGI
3.89E − 09
2.59E − 08
1.15E − 09
3.82E − 08
LC 50
1.17E − 08
1.29E − 07
1.02E − 08
1.02E − 07
MEL-28
GI 50
2.59E − 09
2.59E − 09
2.55E − 10
3.82E − 09
2.78E − 09
2.16E − 09
TGI
3.89E − 09
1.03E − 08
6.37E − 10
1.27E − 08
7.16E − 09
5.23E − 09
LC 50
1.04E − 08
2.59E − 08
1.15E − 09
6.37E − 08
4.70E − 08
1.26E − 08
OVCAR
GI 50
TGI
LC 50
A498
GI 50
2.59E − 09
2.59E − 09
2.55E − 10
3.82E − 09
TGI
6.49E − 09
9.06E − 09
5.10E − 10
1.27E − 08
LC 50
1.30E − 08
5.17E − 08
1.27E − 09
6.37E − 08
DU145
GI 50
1.30E − 09
1.29E − 09
3.82E − 10
2.55E − 09
3.83E − 09
5.41E − 09
TGI
3.89E − 09
2.59E − 09
8.92E − 10
3.82E − 09
1.20E − 08
9.39E − 09
LC 50
9.08E − 09
3.88E − 09
3.82E − 09
1.02E − 08
1.29E − 05
1.30E − 05
MCF
GI 50
2.59E − 09
9.06E − 09
1.02E − 09
5.10E − 09
TGI
5.19E − 09
2.59E − 08
2.55E − 09
2.55E − 08
LC 50
1.17E − 08
1.29E − 07
1.15E − 08
1.27E − 07
MB231
GI 50
1.30E − 09
2.59E − 09
2.55E − 10
3.82E − 09
TGI
5.19E − 09
9.06E − 09
1.27E − 09
1.02E − 08
LC 50
1.30E − 08
9.06E − 08
1.27E − 08
1.27E − 07
H-MEC-1
GI 50
2.60E − 09
8.43E − 08
TGI
3.04E − 08
7.83E − 07
LC 50
1.29E − 05
1.30E − 05
LNCAP
GI 50
8.16E − 10
6.14E − 09
TGI
2.50E − 09
9.48E − 09
LC 50
7.48E − 09
2.51E − 08
SK-OV3
GI 50
4.37E − 09
5.07E − 08
TGI
1.46E − 08
2.05E − 07
LC 50
1.29E − 05
1.30E − 05
IGROV
GI 50
3.45E − 09
3.72E − 09
TGI
7.72E − 09
7.21E − 09
LC 50
3.38E − 06
2.71E − 08
IGROV-ET
GI 50
5.53E − 09
5.03E − 08
TGI
2.35E − 08
1.03E − 07
LC 50
1.29E − 05
1.30E − 07
SK-BR3
GI 50
2.21E − 09
1.18E − 08
TGI
6.55E − 09
3.20E − 08
LC 50
1.09E − 06
8.64E − 08
K562
GI 50
1.14E − 09
6.15E − 09
TGI
2.67E − 09
9.92E − 09
LC 50
1.02E − 08
1.09E − 07
PANC-1
GI 50
4.52E − 09
4.21E − 08
TGI
4.21E − 08
1.04E − 07
LC 50
1.29E − 05
1.30E − 05
LOVO
GI 50
2.26E − 09
2.73E − 08
TGI
5.68E − 09
5.46E − 08
LC 50
1.29E − 08
1.09E − 07
LOVO-DOX
GI 50
2.68E − 08
7.04E − 08
TGI
1.24E − 07
9.77E − 07
LC 50
1.29E − 05
1.30E − 05
HELA
GI 50
TGI
LC 50
HELA-APL
GI 50
TGI
LC 50
[0313]
Compound 37
Compound 38
Compound 39
Compound 40
Compound 41
Compound 42
A549
GI 50
4.23E − 09
2.38E − 09
4.67E − 08
2.41E − 09
1.98E − 08
2.20E − 08
TGI
2.17E − 08
5.24E − 09
8.74E − 08
4.11E − 09
4.68E − 08
4.09E − 08
LC 50
1.38E − 07
1.15E − 08
2.32E − 06
7.02E − 09
1.10E − 07
7.59E − 08
HT29
GI 50
3.71E − 09
4.20E − 09
4.85E − 08
3.26E − 09
5.66E − 09
3.41E − 08
TGI
1.40E − 08
1.69E − 08
1.73E − 05
1.06E − 08
6.07E − 08
1.42E − 07
LC 50
1.27E − 05
1.27E − 05
1.30E − 05
1.30E − 05
1.27E − 05
1.27E − 05
SW-620
GI 50
TGI
LC 50
MEL-28
GI 50
2.40E − 09
2.73E − 09
3.47E − 08
1.96E − 08
6.72E − 09
4.04E − 10
TGI
6.82E − 09
5.33E − 09
6.91E − 08
4.70E − 08
2.66E − 08
9.77E − 10
LC 50
3.35E − 08
1.04E − 08
1.81E − 07
1.12E − 07
1.02E − 07
6.19E − 09
OVCAR
GI 50
TGI
LC 50
A498
GI 50
TGI
LC 50
DU145
GI 50
4.60E − 09
2.04E − 09
5.59E − 08
2.35E − 09
3.49E − 09
3.51E − 09
TGI
1.06E − 08
6.80E − 09
2.03E − 06
6.41E − 09
8.37E − 09
7.97E − 09
LC 50
1.27E − 05
1.27E − 05
1.30E − 05
2.45E − 06
9.90E − 06
1.27E − 08
MCF
GI 50
TGI
LC 50
MB231
GI 50
TGI
LC 50
H-MEC-1
GI 50
2.22E − 09
3.06E − 09
5.81E − 08
2.45E − 09
4.68E − 09
4.04E − 08
TGI
3.58E − 08
8.93E − 09
1.46E − 06
5.31E − 09
4.08E − 08
2.47E − 07
LC 50
1.27E − 05
1.27E − 05
1.30E − 05
1.15E − 08
1.27E − 05
1.27E − 05
LNCAP
GI 50
2.60E − 10
2.00E − 10
2.05E − 08
1.02E − 09
2.62E − 09
3.74E − 09
TGI
8.56E − 10
7.21E − 10
4.41E − 08
2.48E − 09
5.17E − 09
6.61E − 09
LC 50
4.75E − 09
3.07E − 09
9.47E − 08
5.88E − 09
1.02E − 08
1.17E − 08
SK-OV3
GI 50
3.57E − 09
2.55E − 09
6.24E − 08
2.90E − 09
3.85E − 09
7.37E − 09
TGI
1.07E − 08
7.13E − 09
3.19E − 07
6.28E − 09
9.82E − 09
7.92E − 07
LC 50
1.27E − 05
1.27E − 05
1.30E − 05
1.30E − 08
1.27E − 05
1.27E − 05
IGROV
GI 50
2.82E − 09
7.57E − 10
4.30E − 08
1.96E − 09
1.94E − 09
2.44E − 09
TGI
7.06E − 09
2.89E − 09
8.15E − 08
4.17E − 09
4.14E − 09
5.12E − 09
LC 50
6.13E − 07
8.40E − 09
2.32E − 06
8.86E − 09
8.86E − 09
1.07E − 08
IGROV-ET
GI 50
3.76E − 08
1.57E − 08
8.25E − 08
2.42E − 09
3.14E − 09
4.32E − 08
TGI
1.19E − 07
6.59E − 08
4.04E − 06
8.66E − 09
2.00E − 08
9.42E − 08
LC 50
1.27E − 05
6.51E − 06
1.30E − 05
4.80E − 06
3.86E − 06
1.27E − 05
SK-BR3
GI 50
2.96E − 09
1.07E − 09
4.99E − 08
2.56E − 09
2.33E − 09
6.63E − 09
TGI
6.80E − 09
3.38E − 09
1.10E − 07
6.50E − 09
6.86E − 09
2.44E − 08
LC 50
1.41E − 07
9.54E − 09
9.44E − 07
2.80E − 08
3.63E − 08
8.73E − 08
K562
GI 50
4.92E − 10
4.22E − 10
2.51E − 08
8.43E − 10
1.10E − 10
4.77E − 09
TGI
1.36E − 09
8.18E − 10
4.46E − 08
6.87E − 09
2.19E − 09
9.15E − 09
LC 50
1.27E − 08
3.15E − 09
7.92E − 08
8.00E − 08
5.57E − 09
2.81E − 06
PANC-1
GI 50
3.12E − 09
3.22E − 09
6.01E − 08
2.82E − 09
1.08E − 08
1.69E − 08
TGI
1.18E − 08
8.37E − 09
9.22E − 07
7.17E − 09
4.89E − 08
8.25E − 08
LC 50
3.02E − 06
4.28E − 07
1.30E − 05
1.28E − 07
5.06E − 07
1.27E − 05
LOVO
GI 50
2.92E − 09
3.55E − 09
3.21E − 08
2.51E − 09
4.42E − 09
1.35E − 08
TGI
8.97E − 09
1.03E − 08
6.22E − 08
5.98E − 09
2.44E − 08
4.37E − 08
LC 50
1.27E − 05
1.27E − 05
1.20E − 07
2.38E − 08
4.10E − 07
1.27E − 07
LOVO-DOX
GI 50
6.17E − 08
5.53E − 08
2.34E − 07
3.04E − 08
3.05E − 08
4.59E − 08
TGI
4.10E − 07
8.42E − 07
9.94E − 07
9.12E − 08
9.99E − 08
2.05E − 07
LC 50
1.27E − 05
1.27E − 05
1.30E − 05
5.51E − 07
1.27E − 05
1.27E − 05
HELA
GI 50
TGI
LC 50
HELA-APL
GI 50
TGI
LC 50
[0314]
Compound 43
Compound 44
Compound 45
Compound 46
Compound 47
Compound 48
A549
GI 50
5.12E − 09
2.74E − 08
6.89E − 08
3.33E − 08
3.33E − 08
5.56E − 07
TGI
1.08E − 08
4.76E − 08
3.01E − 07
6.78E − 08
7.50E − 08
1.09E − 06
LC 50
3.28E − 08
8.23E − 08
4.47E − 06
3.35E − 07
1.33E − 06
1.26E − 05
HT29
GI 50
4.64E − 08
5.98E − 08
8.78E − 08
4.44E − 08
3.88E − 08
5.01E − 07
TGI
1.04E − 07
4.59E − 07
1.21E − 06
1.22E − 06
1.21E − 05
1.26E − 06
LC 50
1.30E − 05
1.30E − 05
1.21E − 05
1.17E − 05
1.21E − 05
1.26E − 05
SW-620
GI 50
TGI
LC 50
MEL-28
GI 50
3.08E − 07
2.63E − 09
3.07E − 08
1.24E − 08
4.26E − 09
3.59E − 07
TGI
5.81E − 07
5.22E − 09
7.03E − 08
4.07E − 08
1.00E − 08
7.12E − 07
LC 50
1.09E − 06
1.03E − 08
3.78E − 07
1.53E − 07
2.07E − 07
3.09E − 06
OVCAR
GI 50
TGI
LC 50
A498
GI 50
TGI
LC 50
DU145
GI 50
4.76E − 09
6.54E − 09
3.92E − 08
6.48E − 09
5.46E − 09
6.97E − 07
TGI
9.04E − 09
1.18E − 08
9.54E − 08
4.61E − 08
2.06E − 08
1.08E − 05
LC 50
1.30E − 08
1.30E − 05
1.21E − 05
1.17E − 05
1.21E − 05
1.26E − 05
MCF
GI 50
TGI
LC 50
MB231
GI 50
TGI
LC 50
H-MEC-1
GI 50
1.18E − 08
7.53E − 08
4.79E − 08
2.60E − 08
6.78E − 09
5.70E − 07
TGI
1.77E − 07
1.31E − 06
8.41E − 06
1.17E − 06
1.50E − 07
1.26E − 05
LC 50
1.30E − 05
1.30E − 05
1.21E − 05
1.17E − 05
1.21E − 05
1.26E − 05
LNCAP
GI 50
2.02E − 09
4.30E − 09
3.83E − 09
1.17E − 10
2.65E − 09
2.16E − 07
TGI
3.76E − 09
8.84E − 09
1.21E − 08
3.25E − 09
5.08E − 09
4.28E − 07
LC 50
7.00E − 09
3.11E − 08
4.82E − 08
1.75E − 08
9.76E − 09
8.45E − 07
SK-OV3
GI 50
3.39E − 09
3.75E − 08
4.06E − 08
3.06E − 08
8.98E − 09
5.50E − 07
TGI
7.17E − 09
1.31E − 07
1.24E − 07
2.00E − 06
2.88E − 07
1.12E − 06
LC 50
1.30E − 08
1.30E − 05
1.21E − 05
1.17E + 05
1.21E − 05
1.26E − 05
IGROV
GI 50
2.73E − 09
4.29E − 09
4.35E − 08
2.32E − 08
1.06E − 08
4.21E − 07
TGI
5.20E − 09
1.22E − 08
9.49E − 08
5.40E − 08
4.07E − 08
8.32E − 07
LC 50
9.88E − 09
9.30E − 08
2.24E − 06
1.92E − 07
9.09E − 07
5.62E − 06
IGROV-ET
GI 50
9.10E − 09
2.85E − 08
2.33E − 07
4.95E − 08
6.97E − 08
8.76E − 07
TGI
2.35E − 08
7.06E − 08
2.56E − 06
1.29E − 07
3.61E − 06
1.26E − 05
LC 50
1.30E − 05
1.30E − 07
1.21E − 05
7.35E − 06
1.21E − 05
1.26E − 05
SK-BR3
GI 50
3.77E − 09
1.27E − 08
6.68E − 08
1.63E − 08
7.56E − 09
6.11E − 07
TGI
8.65E − 09
4.27E − 08
2.50E − 07
5.84E − 08
3.47E ± 08
1.69E − 06
LC 50
4.11E − 08
1.77E − 07
1.21E − 06
4.12E − 07
6.93E − 07
1.15E − 05
K562
GI 50
2.51E − 09
3.94E − 09
2.13E − 08
1.22E − 06
1.31E − 08
5.01E − 07
TGI
4.88E − 09
9.38E − 09
5.45E − 08
2.02E − 06
2.11E − 06
1.76E − 06
LC 50
9.49E − 09
1.07E − 07
2.10E − 07
3.38E − 06
6.32E − 06
3.55E − 06
PANC-1
GI 50
5.28E − 09
5.67E − 08
2.86E − 08
4.11E − 08
4.24E − 08
7.06E − 07
TGI
1.15E − 08
1.55E − 07
1.15E − 06
2.58E − 07
1.70E − 06
1.21E − 05
LC 50
3.90E − 08
1.30E − 05
1.21E − 05
1.17E − 05
1.21E − 05
1.26E − 05
LOVO
GI 50
3.50E − 09
2.71E − 08
4.29E − 08
1.56E − 08
6.26E − 09
3.22E − 07
TGI
8.32E − 09
5.10E − 08
1.17E − 07
5.70E − 08
4.64E − 08
6.28E − 07
LC 50
3.89E − 08
9.61E − 08
1.21E − 05
1.17E − 05
1.21E − 05
1.22E − 06
LOVO-DOX
GI 50
3.98E − 08
9.10E − 08
3.49E − 07
3.82E − 08
4.07E − 08
1.35E − 06
TGI
1.06E − 07
8.53E − 07
1.03E − 06
2.41E − 07
1.17E − 07
6.21E − 06
LC 50
1.30E − 05
1.30E − 05
1.21E − 05
1.17E − 05
1.21E − 05
1.26E − 05
HELA
GI 50
TGI
LC 50
HELA-APL
GI 50
TGI
LC 50
[0315]
Compound 49
Compound 51
Compound 57
Compound 62
Compound 68
A549
GI 50
2.64E − 06
2.67E − 08
1.03E − 07
8.80E − 09
2.83E − 08
TGI
4.97E − 06
6.11E − 08
6.07E − 07
3.30E − 08
4.95E − 08
LC 50
9.37E − 06
1.29E − 06
1.22E − 05
7.70E − 08
1.01E − 07
HT29
GI 50
4.50E − 06
3.82E − 08
1.65E − 07
1.10E − 08
3.17E − 07
TGI
1.26E − 05
1.31E − 06
1.41E − 06
6.60E − 08
9.59E − 08
LC 50
1.26E − 05
1.11E − 05
1.22E − 05
9.90E − 08
1.17E − 05
SW-620
GI 50
2.20E − 08
TGI
5.50E − 08
LC 50
1.10E − 07
MEL-28
GI 50
2.84E − 08
6.47E − 08
3.30E − 09
7.52E − 09
TGI
5.03E − 08
2.09E − 07
1.10E − 09
2.24E − 08
LC 50
8.93E − 08
6.62E − 07
3.30E − 08
6.72E − 08
OVCAR
GI 50
TGI
LC 50
A498
GI 50
3.30E − 09
TGI
4.40E − 09
LC 50
1.10E − 08
DU145
GI 50
4.83E − 08
4.77E − 08
2.20E − 09
2.99E − 08
TGI
3.23E − 07
1.84E − 06
4.40E − 09
8.65E − 08
LC 50
1.12E − 05
1.22E − 05
9.90E − 09
1.03E − 05
MCF
GI 50
2.20E − 09
TGI
9.90E − 09
LC 50
1.10E − 07
MB231
GI 50
1.10E − 09
TGI
5.50E − 09
LC 50
3.30E − 08
H-MEC-1
GI 50
1.99E − 06
TGI
4.12E − 06
LC 50
8.54E − 06
LNCAP
GI 50
1.31E − 08
3.33E − 08
1.15E − 08
TGI
2.70E − 08
7.17E − 08
2.66E − 08
LC 50
5.48E − 08
2.32E − 08
6.13E − 08
SK-OV3
GI 50
TGI
LC 50
IGROV
GI 50
3.23E − 08
7.18E − 08
2.17E − 08
TGI
6.33E − 08
4.60E − 07
6.16E − 08
LC 50
3.55E − 06
7.43E − 06
1.09E − 06
IGROV-ET
GI 50
2.63E − 07
3.94E − 07
3.08E − 08
TGI
7.47E − 06
1.15E − 06
6.89E − 08
LC 50
1.12E − 05
1.22E − 05
2.06E − 07
SK-BR3
GI 50
3.98E − 08
6.76E − 08
2.90E − 08
TGI
9.93E − 08
3.13E − 07
6.09E − 08
LC 50
3.11E − 06
7.99E − 06
2.06E − 07
K562
GI 50
1.65E − 08
4.77E − 08
2.04E − 08
TGI
4.62E − 08
4.66E − 07
4.47E − 08
LC 50
1.14E − 07
1.22E − 05
9.75E − 08
PANC-1
GI 50
4.19E − 08
1.13E − 07
4.81E − 08
TGI
1.33E − 07
6.62E − 07
1.25E − 07
LC 50
2.00E − 06
1.22E − 05
1.17E − 05
LOVO
GI 50
2.11E − 08
7.30E − 08
2.71E − 08
TGI
3.88E − 08
2.57E − 07
4.97E − 08
LC 50
7.10E − 08
9.05E − 07
9.13E − 08
LOVO-DOX
GI 50
3.81E − 07
4.87E − 07
1.12E − 07
TGI
3.09E − 06
6.70E − 06
7.43E − 07
LC 50
1.12E − 05
1.22E − 05
1.17E − 05
HELA
GI 50
2.40E − 08
4.37E − 08
3.25E − 08
TGI
4.85E − 08
1.46E − 07
6.03E − 08
LC 50
9.80E − 08
6.52E − 07
1.12E − 07
HELA-APL
GI 50
2.91E − 08
6.14E − 08
3.70E − 08
TGI
4.97E − 08
2.03E − 07
6.19E − 08
LC 50
8.46E − 08
8.50E − 07
1.03E − 07
Toxicity Data
[0316] Toxicity was asssessed by the methods reported in Toxicology in Vitro, 15 (2001) 571-577, J. Luber Narod et al.: “Evaluation of the use of in vitro methodologies as tools for screening new compounds for potential in vivo toxicity”.
Methods
[0317] In order to assess the cytotoxicity of the drugs to normal cells, we used 96 well plates plated at a density of 5000 cells per well (except for the FDC-P1 which were plated at 12,000 cells per well) with normal cell lines (ATCC, Table 1) maintained as per the directions of the ATCC: AML-12, normal mouse liver cells; NRK-52E, normal rat kidney cells; L8, normal rat skeletal muscle cells; FDC-Pl, normal mouse myelogeous stem cells; and H9c2 (2-1), normal rat cardiac muscle cells. The cells in each plate were permitted to settle overnight before adding the test drug. In addition, primary neuronal cultures were prepared from embryonic (day e-17) whole brain (forebrain and brainstem) and spinal cord using established methods (Federoff and Richardson, 1997).
[0318] To each well (100 μl medium) 10 μl of drug in media was added at varying concentrations (1×10-10-0.01 mg/ml final concentration) and further incubated overnight at 37° C. with 5% CO2. After 24 h the following assays were performed. All experiments were repeated at least 3 times and were assayed in duplicate.
[0319] 1. MTS assay (CellTiter 96 aqueous) was performed according to the manufacturer's (Promega) directions (for all cell types). Cell viability (mitochondrial activity) is determined via enzymatic conversion of the formazan substrate.
Compound n° Liver Heart Myelo Skeletal Kidney 26 1.06E − 06 6.43E − 07 1.03E − 07 3.71E − 08 4.60E − 08 27 1.48E − 08 9.93E − 08 1.75E − 08 1.54E − 08 1.01E − 08 28 1.42E − 07 1.84E − 07 2.00E − 07 1.45E − 07 8.37E − 08 29 1.59E − 08 7.22E − 08 1.79E − 08 3.29E − 07 1.94E − 08 30 2.72E − 07 5.06E − 07 7.58E − 09 2.51E − 08 4.19E − 09 31 1.89E − 08 6.65E − 08 3.18E − 08 1.35E − 08 4.27E − 08 32 6.00E − 07 2.42E − 07 5.25E − 07 1.51E − 08 1.45E − 07 33 1.05E − 08 1.27E − 06 1.92E − 08 1.41E − 08 7.78E − 09 34 2.55E − 06 4.96E − 07 1.15E − 05 1.48E − 08 2.74E − 07 35 4.88E − 08 1.93E − 08 4.08E − 08 3.07E − 08 3.42E − 08 36 3.19E − 07 8.86E − 07 2.05E − 07 2.71E − 08 3.56E − 07 37 5.46E − 09 1.74E − 08 4.59E − 09 2.22E − 08 2.92E − 08 38 1.39E − 10 2.96E − 09 9.66E − 11 1.29E − 08 9.85E − 08 39 1.14E − 06 NT 4.10E − 07 4.58E − 07 9.88E − 05 40 3.86E − 08 NT 4.08E − 08 2.11E − 07 2.95E − 08 41 6.30E − 08 3.49E − 08 1.39E − 07 2.39E − 07 1.89E − 08 42 1.86E − 07 1.42E − 07 6.41E − 08 3.37E − 08 1.12E − 09 43 7.57E − 08 9.42E − 08 6.23E − 08 1.60E − 07 4.38E − 08 44 4.33E − 07 5.20E − 06 1.21E − 07 4.02E − 08 4.15E − 07 46 5.01E − 08 3.51E − 08 1.17E − 07 2.16E − 07 4.01E − 08 47 3.04E − 08 7.36E − 08 6.76E − 08 2.57E − 08 3.15E − 08
In Vitro Evaluation of the Compounds for ADME-TOX Profile
[0000] Partition Coefficient (Log D)
[0320] The partition coefficient of a chemical compound provides a thermodynamic measure of its hydrophilicity-lipophylicity balance. Lipophilicity is a major structural factor that influences the pharmacokinetic and pharmacodynamic behavior of compounds. The partition coefficient between water or buffer and 1-octanol is the most widely used measure of chemical compound lipophilicity.
[0321] The measurement of partition coefficient was evaluated based on a miniaturized shake-flask procedure. Buffer (Dulbecco's PBS, pH 7.40) was used as the aqueous phase. The tested compound was dissolved in DMSO, at the concentration of 100 μM. The final DMSO concentration (1%.) during the octanol-buffer partitioning are very low to avoid bias on the partitioning. The amount of compound in the buffer phase was determined by HPLC with photodiode array detection after an equilibration phase of 60 min. The amount of compound in the octanol phase is calculated by subtraction of the amount of compound in buffer from the total amount of compound, which is determined from a calibration sample.
[0322] Log D is calculated as the Log10 of the amount of compound in the octanol phase divided by the amount of compound in the buffer phase. The effective range of the log D microassay is approximately −0.5 to +4.5.
In Vitro Intestinal Absorption Assays
[0323] The intestinal epithelium permeability is a critical characteristic that determines the rate and extent of human absorption and ultimately the bioavailability of a drug candidate. Caco-2 permeability assay allows a rapid assessment of membrane permeability and thus helps to rank-order compounds in terms of their absorption potential.
[0324] The Caco-2 cell line is a human colon adenocarcinoma cell line that differentiates in culture and resembles the epithelial lining of the human small intestine. It has been widely used as an in vitro intestinal epithelial model for drug transport and permeability screening of discovery compounds.
[0325] The apparent permeability coefficients (P app ) was determined in the apical-to-basolateral (A-to-B) direction across the cell monolayers (TC-7 sub-clone of the Caco-2) cultured on polycarbonate membrane filters. Compounds were tested at 50 μM with at a final DMSO concentration of 1%. Samples were analyzed by HPLC-MS or HPLC-MS/MS.
[0326] The test compound was added to the apical side and the P app was determined based on the rate of appearance of the test compound in the basolateral side after 2h-incubation. Two reference compounds, propranolol (highly permeable) and ranitidine (poorly permeable), are tested in each assay as controls. Results from this assay can be used to rank-order compounds in terms of their absorption potential. Compounds with P app equals to or greater than 20×10-6 cm/s could be considered highly permeable and are likely to be “not permeability-limited”. Compounds with P app less than 5×10-6 cm/s are considered poorly permeable and are likely to be “permeability-limited”. Compounds with P app greater than 5×10-6 but less than 20×10-6 cm/s” are considered to have medium permeability.
Metabolism
[0327] Hepatic metabolism is a primary determinant of pharmacokinetic behavior, and rapid first-pass metabolism is a major cause of low bioavailability. Pooled liver microsomes and recombinant cytochrome P450's are used for the metabolic assessment of hits, leads, and new pharmaceutical compounds. The results of the metabolic screening studies are useful in:
Determining the initial rate at which compounds are metabolized Investigating the major pathways of drug metabolism Predicting in vivo pharmacokinetic behavior Investigating the potential for drug-drug interactions
[0332] The metabolic stability was determined used human liver S9 homogenate that including both microsomal and cytosolic enzyme activities. The test compound was diluted in methanol (0.625%) and acetonitrile (0.625%) at the concentration 1 μM and incubated in the human liver pool (protein=1 mg/mL) during 60 min at 37° C. Peak areas corresponding to all analytes (metabolic products) were determined by HPLC-MS/MS. Areas were recorded and ratios of peak areas of analytes to that of internal standard for each analyte were determined. The ratio of precursor compound remaining after 60 minutes and the amount remaining at time zero, expressed as percent, are reported as metabolic stability. Higher values mean higher metabolic stability.
Inhibition of Cytochromes P450 (CYP450)
[0333] The cytochromes P450 are a group of related enzymes primarily located in the liver and responsible of the metabolism of drugs. The inhibition of these CYP by drugs are related with drug-drug interactions and toxicities.
[0334] CYP3A4 is the most common form of the CYP3A enzymes found in adults and is the form implicated in most drug interactions. CYP2D6 metabolize more than 25% of the clinically useful medications.
[0335] For CYP2D6 inhibition assay, the compound are tested at 10 μM in duplicate with a 0.25% final concentration of both methanol and acetonitrile in presence of the fluorescent substrate AMMC (3-[2-N,N-diethyl-N-methylammonium)ethyl]-7-methoxy-4-methylcoumarin) at the concentration of 1.5 μM). The conversion of the AMMC in AHMC (3-[2-N,N-diethyl-N-methylammonium)ethyl]-7-hydroxy-4-methylcoumarin) is determined spectrofluorimetry after incubation with the enzyme during 450 min at 37° C.
[0336] For CYP3A4 inhibition assay, the compound were tested at 10 μM in duplicate with a 0.25% final concentration of both methanol and acetonitrile in presence of the fluorescent substrate BFC (50 μM). The conversion of the BFC (7-benzyloxy-4-trifluoromethylcoumarin) in HFC (7-hydroxy-4-trifluoromethylcoumarin) was determined spectro-fluormetry after incubation with the enzyme during 30 min at 37° C.
[0337] For both assays, the fluorescent intensity measured at t=0 is subtracted from that measured after the appropriate incubation time. The ratio of signal-to-noise is calculated by comparing the fluorescence in incubations containing the test compound to the control samples containing the same solvent vehicle. The percent of control activity is calculated and reported as percent inhibition.
In vitro Safety Assessment. Cell Viability
[0338] The toxic potential of compounds was investigated in vitro using primary human hepatocytes (HEPG2). The compounds were tested at 30 μM in duplicate with a final DMSO concentration of 1%. After incubation during 24 h at 37° C. the cell viability was determined by the conversion of oxided alarmarBlue (resazurin) to reduced alarmarBlue (resorufin). Chlorpromazine was used as reference compound. Results are expressed as a percent of inhibition of control values.
Results of the Studies ADME-TOX
[0339]
Relative
Perme-
Peak Area
ability
of Principal Peak
Solubility
log D
A to B
(Chromatographic
Dulbecco's
n-Octanol-
TC 7 Cells
Purity)
PBS pH 7.4
Dulbecco's
P app (10 −6
Compound
(%)
(μM)
PBS pH 7.4
cm/s)
31
97.4
18.28
3.61
<0.32
35
99.0
<1 est
>5.0
PD
26 (ET-736)
62.9
<1 est
>5.0
PD
27
84.9
2.99
>5.0
<1.18
34
98.6
17.65
>5.0
5.00
33
82.6
68.94
3.50
7.77
28
88.8
<1 est
>4.6
ND
29
97.5
1.59
>4.9
ND
30
100.0
2.24
>4.9
ND
32
92.8
14.28
>4.3
PD
36
98.4
26.03
>4.4
PD
43
96.0
5.85
>4.5
ND
44
97.4
20.69
>4.9
PD
41
92.9
<1 est
>4.5
ND
42
96.8
10.37
>4.8
PD
46
95.9
1.37
>5.0
PD
47
87.4
<1 est
>5.0
PD
[0340]
Human Liver S9
Cell
Metabolic
CYP2D6
CYP3A4
Viability
Stability
(%
(%
(%
Compound
(% remaining)
inhibition)
inhibition)
inhibition)
31
17
—
84
22
35
4
—
24
23
26 (ET-736)
3
12
45
—
27
7
13
53
—
34
24
28
80
45
33
10
28
84
32
28
33
34
79
17
29
9
27
55
29
30
6
—
25
—
32
9
12
83
39
36
2
15
78
33
43
3
—
15
—
44
4
16
72
73
41
7
16
22
16
42
5
19
78
67
46
7
16
60
33
47
5
10
38
18 | Derivatives of ecteinascidin 736 of general formula (I) wherein the groups R 1 , R 2 , R 3 , R 4 and R 5 are each independently selected from the group consisting of H, OH, OR′, SH, SR′, SOR′, SO 2 R′, C(═O)R′, C(═O)OR′, NO 2 , NH 2 , NHR′, N(R′) 2 , NHC(O)R′, CN, halogen, ═O, substituted or unsubstituted C 1 -C 25 alkyl, substituted or unsubstituted C 2 -C 18 alkenyl, substituted or unsubstituted C 2 -C 18 alkynyl, substituted or unsubstituted arly, substituted or unsubstituted heterocyclic; wherein X is independently selected of OR′, CN, (═O), or H; wherein each of the R′ groups is independently selected from the group consisting of H, OH, NO 2 , NH 2 , SH, CN, halogen, ═O, C(═O)H, C(═O)CH 3 , CO 2 H, substituted or unsubstituted C 1 -C 25 alkyl, substituted or unsubstituted C 1 -C 18 alkenyl, substituted or unsubstituted C 2 -C 18 alkynyl, substituted or unsubstituted aryl; wherein m is 0, 1 or 2; and wherein n is 0, 1, 2, 3, or 4, and their use as antitumoral agent. | 2 |
TECHNICAL FIELD
The present invention broadly relates to clamping mechanisms for holding a substrate such as a semi-conductor wafer during processing in a vacuum chamber, and deals more particularly with an improved clamp that reduces the tendency of the clamp to adhere to the substrate when the substrate is released for removal from the chamber, as well as to a related method of producing the clamp.
BACKGROUND ART
In the field of semi-conductor processing, various types of processing equipment are now in widespread use which provide for automated handling of wafers in the vacuum chambers where the processing is carried out. Common semi-conductor processes performed in vacuum environments include the deposition of metallic layers on the surface of the wafer, sometimes known as physical vapor deposition (PVD) or sputtering, selective epitaxial deposition, chemical vapor deposition (CVD), plasma etching, ion implantation, etc. These processes typically involve the use of one or more load-lock vacuum chambers in which the wafers are processed, following which they are removed from the chambers.
At a process station within the chamber, is often necessary to hold the wafer firmly against a support surface, typically a heating assembly, in order to maintain the position of the wafer relative to the processing equipment, or to maintain good thermal contact with the heating assembly. A common technique for maintaining the temperature of a wafer undergoing processing in a vacuum environment is to introduce a conductive gas in a narrow space at the back side of the wafer, thereby thermally coupling the wafer to a temperature control element. When using a backside gas, which is introduced at a pressure higher than the ambient pressure within the processing chamber, clamping means are required to ensure that the backside gas does not move the wafer off of the support surface.
In many cases, the particular process used in the process chamber may cause the clamp to adhere to a wafer after completion of a processing step, thus preventing the wafer from being picked up by a robot arm or other transport mechanism. This may occur, for example, when depositing a metal layer over a wafer which causes the wafer to stick to the clamp, or where a top layer of material on the wafer melts or becomes plastic at an elevated temperature used in a processing step, thus causing the top layer to adhere to the clamp. In some cases, repeatedly deposited film, such as a photoresist, accumulates on surfaces of the clamp, thus also tending to cause the wafer to adhere to the clamp.
When a wafer sticks to a clamp, the entire processing system typically must be shut down to free the stuck wafer. This remedial procedure requires the process chamber to be vented and partially disassembled so that the wafer can be manually dislodged from the clamp. This procedure can require several hours of time, and with the additional time required to evacuate and cleanse the chamber, a stuck wafer can result in down time of four to five hours. This naturally reduces wafer throughput of the entire processing system, and results in corresponding revenue losses.
Others in the past have attempted various solutions to the wafer sticking problem described above. For example, one approach involves providing a slightly beveled surface on the clamp so that only the outer most edge of the wafer is contacted, as far as from the deposition process as possible. An overhang or "hood" is formed by the projection of the beveled edge which tends to block sputtered material from reaching the area where the clamp makes physical contact with the wafer. This beveled surface or hood does not, however, completely eliminate the possibility of sticking, because after processing a series of batches, the deposited material tends to accumulate, eventually building up back into the area where the clamp contacts the wafer's edge. Even more serious are those instances where certain films have been deposited onto the entire surface of the wafer and the clamp is applied directly over the deposited film in a subsequent processing step, thus bringing the film and clamping surface into direct contact with each other.
Another attempt at solving the wafer sticking problem is described in U.S. Pat. No. 5,513,594 issued May 7, 1996 to McClanahan. The McClanahan patent discloses the use of a spring-loaded releasing mechanism which applies a biasing force tending to force the wafer away from the clamp upon the release of the clamp. This solution is not entirely satisfactory, however, because of the need to use small springs and mechanisms which add to the complexity for the clamp and potentially reduce reliability. Moreover, spring-loaded release of the wafer from the clamp can result in damage to the wafer or dislodgement of deposited particles that are dispersed into the chamber and can may interfere with subsequent processing steps.
It is therefore a primary object invention to provide a novel semi-conductor wafer clamp which resists adhering to a wafer, thus overcomes the shortcomings of the prior art.
Another object of the present invention is to provide a semi-conductor wafer clamp as described above which provides for ready release of wafers without the need for additional structure or complex mechanisms.
Another object of the present invention is to provide a semi-conductor wafer clamp which is effective in releasing wafers in spite of the fact that deposited films and materials come into mutual contact with both the wafer and the clamp.
A further object of the present invention is to provide a novel method for preventing a wafer clamp from adhering to deposited materials, while also preventing build-up on the clamp of a film formed from the deposited materials.
As a corollary of the foregoing object, another object of the invention is to provide a method of treating at least portions of the surfaces of a semi-conductor wafer clamp which substantially reduces the tendency of the clamp surfaces to stick to the wafer. These, and further objects and advantages of the invention will be made clear or will become apparent during the course of the following description of a preferred embodiment of the present invention.
SUMMARY OF THE INVENTION
In accordance with one aspect of the invention, a novel non-sticking semi-conductor wafer clamp is provided which exhibits markedly improved wafer release characteristics. These improved release characteristics are achieved by treating those surfaces of the clamp which engage or are in proximity to the wafer, so as to achieve a desired surface roughness. Generally, a surface roughness of at least 100 μm is preferred. The desired surface roughness may be achieved by ordinary machine operations such as surface grinding, or by using etching techniques.
According to another aspect of the invention, a method is provided for preventing a wafer clamp from adhering to a wafer, or materials deposited onto the wafer, which involves treated the surfaces of the clamp to achieve a desired surface roughness.
BRIEF DESCRIPTION OF THE DRAWINGS
In the drawings, which form an integral part of the specification and are to be read in conjunction therewith, and in which like reference numerals are employed to designate identical components in the various views:
FIG. 1 is a combined diagrammatic and sectional view of a target, a silicon wafer and a clamping ring in accordance with the preferred embodiment;
FIG. 2 is an enlarged, fragmentary view of a portion of the clamping ring shown in FIG. 1;
FIG. 3 is a view similar to FIG. 2, but showing a layer of photoresist clamped between the wafer and the clamping ring;
FIG. 4 is a top view of a portion of the clamping ring disposed over the wafer before etching of a photoresist;
FIG. 5 is a view similar to FIG. 4, but following etching of the photoresist and removal of the clamping ring.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring first to FIGS. 1 and 2, the present invention relates to an improved wafer clamp in the form of a clapming ring 16, and method for making the same, which is useful in clamping a semi-conductor wafer 10 onto a support, such as the heating element assembly 12 that is disposed within a vacuum chamber adapted to perform PVD, CVD, ion implantation or other similar processes. A target or sputter source 20 is positioned to face the wafer 10. Other major components of the processing chamber are well-known and need not be described here, although those skilled in the art will appreciate that these components will typically include a stainless steel, vacuum tight chamber equipped with a helium leak detector, a pump having the capacity to reduce the chamber pressure to a desired level, pressure gauges, a power supply and wafer holder, which is depicted in FIGS. 1 and 2 as forming a part of the heating assembly 12. In the case of a PVD process, inert gas particles in the chamber, such as argon, are first ionized in an electrical field producing a gas plasma and are attracted toward the target 20 where the energy of these gas particles physically dislodges atoms of the target material, The shape of the sputtered material distribution 22 depicted in FIG. 1 will depend upon the particular target material, In any event, the particles from the target 20 are deposited onto the wafer 10 and result in the build-up of a film layer 14 of the target material. Layer 14 wilt be generally uniform except for the outer edges which are tapered for reasons discussed below.
The wafer clamping ring 16 serves two purposes in the process chamber. The first purpose is to clamp the wafer 10 to the heating assembly 12. This holds the wafer 10 in place when a positive gas pressure is applied between the heater assembly 12 and a supporting pedestal 13, and thus allows the heat to be effectively conducted between the wafer 10 and heating assembly 12. The second purpose of the clamping ring 16 is to create a predetermined leak rate of the inert gas from beneath the wafer 10 into the process chamber.
The clamping ring 16 is generally ring-shaped, and has a cut-out in its center which is oriented to match the flat contour of the wafer 10. A bevel in the clamping ring is provided near its inner circumference to define a hood 18 which overhangs and covers the outer periphery of the wafer 10, around the latter's entire circumference. The hood 18 effectively shadows the outer periphery of the wafer 10 and tends to protect the outer clamping surface 26 of the clamping ring 16 from being coated by the deposited material. Without the hood 18, an inordinant amount of material would be deposited near the periphery of the wafer 10, which in turn would tend to weld the wafer 10 to the clamping ring 16. When welding occurs between the clamping ring 16 and the wafer 10, severe contamination by particles occurs when the wafer 10 is broken from the clamping ring 16, thereby leading to lower yields of wafer production.
Notwithstanding the use of the hood 18, some amounts of the deposited material, is shown by the numeral 28 and FIG. 2, may nevertheless occur, which are contiguous to and tend to bond the clamping ring 16 and the wafer 10.
The problem of the wafer sticking to the clamp is even more severe in certain types of processes where substantial amounts of deposited materials contact both the wafer and the clamp. For example, referring now to FIGS. 3-5, in the case of an ion implantation process, a layer of photoresist 30 is applied to the surface of a wafer 10, which is later etched away, leaving a ring-shaped layer 30 of photoresist which is clamped directly between the clamping surface of the clamping ring 16 and the wafer 10. In FIG. 4, it can be seen that the ring-shaped clamp 30 overlies the wafer 10, with the amount of overhang of the hood 18 being represented by the letter "A", and the width of the ring-shaped surface of the clamping ring 16 actually contacting and clamping the wafer 10 being indicated by the letter "B". As shown in FIG. 5, with the clamping ring 16 removed, there remains on the surface of the wafer 10, a ring-shaped layer of the photoresist 30. Because this layer 30 of photoresist comes into repeated contact with the clamping surface 26, a residual amount of the photoresist tends to stick to the surface of the clamping ring 16 and accumulates there until it begins to interfere with the release of the wafer 10 from the clamping ring 16.
It has been discovered that the adherence and build-up of deposited materials on the surfaces of the clamping ring 16 can be controlled by creating a desired surface finished on the affected clamping surfaces. Specifically, it has been found that surface roughnesses above a minimum value significantly reduce the tendency of the deposited materials to adhere to the clamping ring 16. The exact surface roughness will depend upon the material used as the clamping ring 16 and the materials being deposited, however, generally the surface roughness should be at least 100 μm and can be up to 1000 μm. The desired surface roughness can be achieved by any of several techniques, including surface grinding, or other machining techniques, or etching. In the case of semi-conductor processing where it is desired to avoid adherence of photoresist to the clamping ring 16, a surface roughness of at least 100 μm has been found to be effective.
From the foregoing description, it is apparent that the present invention not only provides for the accomplishment of the objects of the invention, but does so in a particularly simple and economical manner. It is recognized, of course, that those skilled in the art may make various modifications or additions to the preferred embodiments chosen to illustrate the invention without departing from the spirit and scope of the present contribution to the art. Accordingly, it is to be understood that the protection sought and to be forwarded hereby should be deemed to extend to the subject matter claimed and all equivalents thereof within the scope of the invention. | A clamp used in clamping semi-conductor wafers during processing operations permits ready release of the wafer and avoids adherence of the clamp to materials deposited onto the wafer which otherwise tend to stick the wafer to the clamp. Adhesion of the deposited materials to the clamp is avoided by providing the clamping surfaces of the clamp with a minimum surface roughness achieved by machining, grinding, etching or other techniques. | 2 |
RELATED APPLICATION DATA
This application is the U.S. national stage of PCT/US04/05163 filed on Feb. 19, 2004, which is based on and claims the benefit of U.S. Provisional Patent Application No. 60/449,167 filed on Feb. 20, 2003, which is incorporated herein in its entirety by this reference.
INTRODUCTION
Financial assistance for this invention was provided by the United States Government, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Department of Health and Human Services Outstanding Investigator Grant Numbers R01-CA9044-01 and CA44344-05-1-12; the Arizona Disease Control Research Commission; and private contributions. Thus, the United States Government has certain rights in this invention.
FIELD OF THE INVENTION
This invention relates to the isolation from natural sources, and elucidation of the structure of, a compound having antineoplastic, antibacterial and antifungal properties.
BACKGROUND OF THE INVENTION
Marine porifera have continued to be an increasingly important source of new nitrogen heterocyclic compounds with significant biological activities. Recent examples include the cytotoxic constituents pateomine ( Mycale sp.), a pyridine betaine ( Microcosmus vulgaris ), topsentin B2 ( Rhaphisia lacazei ), asmarine A ( Raspailia sp.), cyclic guanidines ( Monanchora sp.), the antiviral dragmacidin F ( Halicortex sp.) and the isolation and structure determination of cribrostatins 4 (1) and 5 (2) from the Republic of Maldives blue-colored sponge Cribrochalina sp. (West, L.; et al., J. Org. Chem. 2000, 65, 445-449; Aiello, A., et al., J. Nat. Prod. 2000, 63, 517-519; Casapullo, A., et al., J. Nat. Prod. 2000, 63, 447-451; Yosief, T., et al., J. Nat. Prod. 2000, 63, 299-304; Braekman, J., et al., J. Nat. Prod. 2000, 63, 193-196; Cutignano, A., et al., Tetrahedron 2000, 56, 3743-3748, Pettit, G., et al., J. Nat. Prod. 2000, 6, 793-798.)
SUMMARY OF THE INVENTION
The present invention relates to the elucidation of the molecular structure for a novel compound denominated Cribrostatin 6, as well as to a method for isolating the compound Cribrostatin 6 from the Marine organism Cribrochalina sp. Cribrostratin 6 exhibits antineoplastic, antibacterial and antifungal properties. Accordingly, the invention also relates to the use of Cribrostatin 6 as a pharmaceutical agent for the treatment of neoplastic disease, as well as for the treatment of bacterial and fungal infections.
DESCRIPTION OF THE DRAWINGS
FIG. 1 illustrates the solid-state structure of Cribrostatin 6.
FIG. 2 illustrates the chemical structures of Cribrostatins 1, 2, 3, 4, 5 and 6.
DETAILED DESCRIPTION OF THE INVENTION
Earlier we had observed a number of biologically active blue to black colored fractions arising during P388 lymphocytic leukemia guided separations of a 195 g dichloromethane-soluble portion of the extract obtained from 350 kg (wet wt.) of Cribrochalina sp. The cancer cell growth (P-388) inhibitory dark-colored fractions were finally separated by a successive series of gel permeation and partition chromatographic techniques on Sephadex LH-20. That sequence was followed by high-speed countercurrent distribution using an Ito Coil-Planet centrifuge to afford 88 mg of a dark-blue constituent (P388 ED 50 0.3 μg/ml), designated cribrostatin 6 (3). Owing to difficulties in unequivocally deducing the structure of this interesting substance based on spectral evidence, attempts were made at various times over a ten year period to reach a correct solution and/or to produce crystals suitable for X-ray structure determination. We were eventually pleased to find that cribrostatin 6 (3) would crystallize from acetone following long cold storage of the solution. To follow is a summary of the spectral and X-ray crystallographic interpretation that completed a correct structural assignment for cribrostatin 6 (3).
Results and Discussion
The molecular formula of cribrostatin 6 (3) was established as C 15 H 14 N 2 O 3 by HRMS, using an APCI inlet system. Inspection of the 1 H and APT NMR spectra indicated the presence of three methyls, one methylene, three methines and eight quaternary carbons. Protonated carbons were assigned using a HMQC experiment. The APT spectrum indicated that four of the carbons were oxygenated and suggested the presence of the quinone. An HMBC experiment allowed placement of the C-9 ethoxy (H-13 to C-9) and C-8 methyl (H-12 to C-7, 8, and 9) groups and established the positions of the quaternary carbons at C-8 and 9 as well as the carbonyl carbons at C-7 and 10, which were assigned by analogy with known isoquinolinequinones such as the Saframycins. (Cooper, R., et al., Antibiotics 1985, 38, 24-30). This accounted for five of the ten degrees of unsaturation determined from the molecular formula. The nature of the B ring was established by 1H-1H COSY, which indicated the presence of a double bond. The HMBC spectrum showed connectivities from the proton at H-6 to C-6a, 7 and 10a as well as establishing the position of the double bond at Δ, which was confirmed by HMBC correlations from H-5 to C-6 and 6a. (Braekman, J., et al., J. Nat. Prod. 2000, 63, 193-196; Cutignano, A., et al., Tetrahedron 2000, 56, 3743-3748.) The remaining three degrees of unsaturation and the fragment C 3 H 4 N 2 suggested an imidazo-partial structure for a C ring. The overall structure was determined by X-Ray diffraction on a small needle-shaped crystal. Although the overall connectivity could be readily established, the low observed data-to-parameter ratio did not permit a clear distinction between structures 3 and 4. Analogy to previous cribrostatin-related compounds (cf. 1, 2) gave the location of one of the N atoms at position 4 with reasonable certainty (Pettit, G., et al., J. Nat. Prod. 2000, 6, 793-798; Pettit, G., et al., Can. J. Chem. 1992, 70, 1170-1175), but conclusive structural assignment as 9-ethoxy-3,8-dimethyl-imidazo[5,1-a]isoquinoline-7, 10-dione (3) required further, more detailed analysis of earlier and new NMR data.
Examination of the HMBC spectrum showed correlations from H5 to C-3 and C10b and implied placement of a nitrogen at position 4. A strong correlation from the remaining methine proton to C-3 suggested position 1 with the remaining nitrogen at position 2. An additional correlation from H-11 to C-3 located the remaining methyl group (δ2.75p) at C-3. A DPFGSENOE (GOESY) experiment demonstrated NOE enhancement between H-5 and H-11 that would be consistent with either structure 3 or 4, but gave no indication of an enhancement between H-2 and H-11, that would be expected to exist in structure 4 (Stonehouse, J., et al., J. Amer. Chem. Soc. 1994, 116, 6037-6038). Measurement of 15 N- 1 H HMBC showed two strong 3-bond correlations from the methyl protons H11 to both nitrogens N2 and N4. HMBC correlations were observed H5 and H6 to N4, but not N2. H1 showed weak correlations to both N2 and N4. Only structure 3 is consistent with these results.
In addition to cancer cell growth inhibition of murine P388 lymphocytic leukemia and human cancer cell lines (see Table II), cribrostatin 6 exhibited antimicrobial activity against numerous antibiotic-resistant Gram-positive bacteria and patlhogenic fungi (see Table III). The only Gram-negative bacterium of those tested which was inhibited by cribrostatin 6 was Neisseria gonorrhoeae . Cribrostatin 2 has an antimicrobial profile similar to cribrostatin 6, while cribrostatins 1, 3, 4 and 5 have antibacterial but not antifungal activities. (Pettit, G., et al., J. Nat. Prod. 2000, 6, 793-798). Thus, the inventors believe that the cribrostatins, particularly cribrostatin 6, warrant further investigation as antibacterial and/or antifungal agents.
Recently, two phosphorylated sterol sulfates were isolated from a Cribrochalina sp. and found to be membrane-type metalloproteinase (MT1-MMP) inhibitors. (Fujita, M., et al., Tetrahedron 2001, 57, 3885-3890.) That advance extends the structural variety of Cribrochalina genus cell growth regulatory constituents that so far range from acetylenic alcohols to quinones (cf. 3) and peptides. (Hallock, Y., et al., J. Nat. Prod. 1995, 58, 1801-1807; Garcia, J., et al. Tetrahedron: Asymmetry 1999, 10, 2617-2626; Sharma, A.; et al., S. Tetrahedron: Asymmetry 1998, 9, 2635-2639; Pettit, G., et al., J. Nat. Prod. 2000, 6, 793-798; Pettit, G., et al., Can. J Chem. 1992, 70, 1170-1175; Yeung, B., et al., J. Org. Chem. 1996, 61, 7168-7173.)
Experimental Section
General Experimental Methods. Except as noted, the general experimental procedures employed in our original investigations of the Cribrochalina sp. were continued here. For discussion of these original investigations, see Pettit, G., et al., J. Nat. Prod. 2000, 6, 793-798; and Pettit, G., et al., Can. J Chem. 1992, 70, 1170-1175, which are incorporated herein by reference. NMR spectra were recorded using a Varian Inova system equipped with a 5 mm triple resonance triaxial PFG probe at 500 MHz for 1 H and 125 MHz for 13 C, and 50.65 MHz for 15 N. 15 N- 1 H gradient HMBC experiments were performed on 2.2 mg of sample dissolved in 100 μl CDCl 3 using a Shigemi 3 mm NMR tube susceptibility matched to CDCl 3 , a Nalorac 3 mm 1 H{ 15 N- 31 P} indirect-detection probe and delays optimized for coupling constants of 90 Hz (1-bond) and 5 Hz (multiple-bond). The 15 N spectra were referenced to formamide (112 pm downfield of liquid ammonia). (Martin, G. et al., J. Nat. Prod. 2000, 63, 543-585.) The 1 H NMR and 13 C NMR spectra were referenced to residual solvent signals at 7.25 and 77.0 ppm for CDCl 3 . HRMS data was obtained using a JEOL LCMate magnetic sector instrument in the APCI mode, calibrated using a polythylene glycol reference mixture. The X-Ray data collection was accomplished using a Bruker AXS 6000 diffractometer.
Isolation of Cribrostatin 6 (1). The blue marine sponge Cribrochalina sp. was collected and extracted as known to one of skill in the art, as described in Pettit, G., et al., J. Nat. Prod. 2000, 6, 793-798 and Pettit, G., et al., Can. J. Chem. 1992, 70, 1170-1175, which is incorporated herein by reference. Fractionation of the extract, guided by the blue color, and the screening results obtained using the murine P-388 lymphocytic leukemia cell line, was carried out on columns of Sephadex LH-20, eluted successively with a.) CH 3 OH; b.) CH 2 Cl 2 —CH 3 OH (3:2); c.) hexane-toluene-CH 3 OH (3:1:1); and d.) hexane/i-PrOH-CH 3 OH (8:1:1). In preparation for a separation using high-speed countercurrent distribution on an Ito Coil-Planet centrifuge, the blue fraction from the previous column was triturated with the upper (less polar) phase of the system hexane-EtOAc-CH 3 OH-water (700:300:150:60), and the solution was filtered. The sparingly-soluble material thus obtained (35.7 mg) proved to be the same as the solid isolated from the principal blue fraction from the countercurrent run (53 mg). The two were combined and recrystallized from acetone to afford dark-blue needles: mp 169-171° C.; P-388 ED 50 0.3 μg/ML; λ max 203 (26,758), 266 (24,432), 323 (5597), 552 (1479); IR v max 2920, 1660, 1620, 1605, 1522, 1170 cm −1 ; 1 H and 13 C-NMR, see Table I; LREIMS (m/z) 270, 242, 214, 185, 172, 157, 145, 116; HRMS (APCI + ) 271.10968 (calcd for (M+H) + ion C 15 H 15 N 2 O 3 , 271.10828 error 5.2 ppm).
Crystal Structure of Cribrostatin 6 (3). All data including atomic coordinates, thermal parameters, bond distances, angles, and observed and calculated structure factors have been deposited in the Cambridge Crystallographic Data Centre and can be obtained, free of charge, on application to the Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44-(0)1223-336003 or e-mail: [email protected]). A very small, dark-blue needle obtained via slow evaporation of an acetone solution, with approximate dimensions of (0.05×0.05×0.20 mm), was mounted on the tip of a glass fiber. An initial set of cell constants was calculated from reflections harvested from three sets of 60 frames at 298(2) K on a Bruker 6000 diffractometer. Cell parameters indicated an orthorhombic space group. Subsequent data collection, using 30 second scans/frame and 0.396° steps in Ω, was conducted in such a manner as to completely survey a complete hemisphere of reflections. This resulted in >93% coverage of the total reflections possible to a resolution of 0.83. A total of 10229 reflections were harvested from the total data collection and final cell constants were calculated from a set of 332 strong, unique reflections. Subsequent statistical analysis of the complete reflection data set using the XPREP program indicated the space group was Pca2 1 . The XPREP program is an automatic space determination program included in the SHELXTL-NT-Version 5.10 (1997), which an integrated suite of programs for the determination of crystal structures from diffraction data, that is available from Bruker AXS, Inc., Madison, Wis. 53719, USA. This package includes, among others, XPREP, SHELXS (a structure solution program via Patterson or direct methods), and SHELXL (structure refinement software).
Crystal data: C 15 H 14 N 2 O 3 , a=15.414(15), b=11.532(11), c=7.201(7) Å, V=1280(2) Å 3 , λ=(Cu Kα)=1.54178 Å, μ (Cu K)=0.817 mm −1 , ρc=1.403 g cm −3 for Z=4 and M r =270.28, F (000)=568. After data reduction, merging of equivalent reflections and rejection of systematic absences, 1885 unique reflections remained (R int =0.5248), of which 315 were considered observed (I o >2 (I o )) and were used in the subsequent structure solution and refinement. An absorption correction was applied to the data with SADBS. (Blessing, R., Acta Cryst., 1995, A51, 33-8.) Direct methods structure determination and refinement were accomplished with the SHELXTL NT ver.V5.10 suite of programs. All non-hydrogen atoms for cribrostatin 6 (3) were located using the default settings of that program. Although the overall connectivity of the non-hydrogen atoms in quinone 3 could be readily established from the X-ray data, the low observed data-to-parameter ratio did not allow a completely unambiguous assignment of the two nitrogen atoms. The location of one of the N atoms at position 9 ( FIG. 1 ; X-ray numbering system) was known with reasonable certainty (due to analogy to previous cribrostatin related compounds), the position of the second N atom was less certain, with positions 11 and 12 both being likely candidates. Refinement of each of these possible isomeric structures (i.e., structures 3 or 4) resulted in nearly identical residual R 1 values (0.0982 vs 0.1002, respectively). Although the former (3) was slightly favored by these results, the final, conclusive structural assignment was based on observed 15 N-NMR experiments. Since the quality of data precluded the direct determination of hydrogen atom positions, the remaining hydrogen atom coordinates were calculated at optimum positions using the program SHELXL. These latter atoms were assigned thermal parameters equal to either 1.2 or 1.5 (depending upon chemical type) of the Uiso value of the atom to which they were attached, then both coordinates and thermal values were forced to ride that atom during final cycles of refinement. All non-hydrogen atoms were refined anisotropically in a full-matrix least-squares refinement process. The final standard residual R 1 value for the model shown in FIG. 1 was 0.0982 (for observed data) and 0.3817 (for all data). The corresponding Sheldrick R values were wR 2 of 0.2174 and 0.2741, respectively. The difference Fourier map showed insignificant residual electron density; the largest difference peak and hole being +0.255 and −0.252 e/Å 3 , respectively. Final bond distances and angles were all within acceptable limits.
Cancer Cell Growth Inhibition
Compounds were screened against a panel of human cancer cell lines and mouse cell lines as is shown in Table II. Cribrostatin 6 exhibited cancer cell growth against all lines illustrated.
Antimicrobial Susceptibility Testing
Compounds were screened against bacteria and fungi according to established broth microdilution susceptibility assays, pursuant to the National Committee for Clinical Laboratory Standards, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically, Approved Standard M7-A4, Wayne, Pa.: NCCLS, 1997, and the National Conmnittee for Clinical Laboratory Standards, Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, Approved Standard M27-A, Wayne, Pa.: NCCLS, 1997. The results of such screening are shown in Table III. The minimum inhibitory concentration was defined as the lowest concentration of compound that inhibited all visible growth of the test organism (optically clear). Assays were repeated on separate days.
ADMINISTRATION
Dosages
The dosage of the presently disclosed compounds to be administered to humans and other animals requiring treatment will depend upon numerous factors, including the identity of the neoplastic disease or microbial infection; the type of host involved, including its age, health and weight; the kind of concurrent treatment, if any; the frequency of treatment and therapeutic ratio. Hereinafter are described various possible dosages and methods of administration, with the understanding that the following are intended to be illustrative only, and that the actual dosages to be administered, and methods of administration or delivery may vary therefrom. The proper dosages and administration forms and methods may be determined by one of skill in the art.
Illustratively, dosage levels of the administered active ingredients are: intravenous, 0.1 to about 20 mg/kg; intramuscular, 1 to about 50 mg/kg; orally, 5 to about 100 mg/kg; intranasal instillation, 5 to about 100 mg/kg; and aerosol, 5 to about 100 mg/k of host body weight.
Expressed in terms of concentration, an active ingredient can be present in the compositions of the present invention for localized use about the cutis, intranasally, pharyngolaryngeally, bronchially, intravaginally, rectally, or ocularly in concentration of from about 0.01 to about 50% w/w of the composition; preferably about 1 to about 20% w/w of the composition; and for parenteral use in a concentration of from about 0.05 to about 50% w/v of the composition and preferably from about 5 to about 20% w/v.
The compositions of the present invention are preferably presented for administration to humans and animals in unit dosage forms, such as tablets, capsules, pills, powders, granules, suppositories, sterile parenteral solutions or suspensions, sterile non-parenteral solutions of suspensions, and oral solutions or suspensions and the like, containing suitable quantities of an active ingredient. Other dosage forms known in the art may be used.
For oral administration either solid or fluid unit dosage forms can be prepared.
Powders are prepared quite simply by comminuting the active ingredient to a suitably fine size and mixing with a similarly comminuted diluent. The diluent can be an edible carbohydrate material such as lactose or starch. Advantageously, a sweetening agent or sugar is present as well as a flavoring oil.
Capsules are produced by preparing a powder mixture as hereinbefore described and filling into formed gelatin sheaths. Advantageously, as an adjuvant to the filling operation, a lubricant such as talc, magnesium stearate, calcium stearate and the like is added to the powder mixture before the filling operation.
Soft gelatin capsules are prepared by machine encapsulation of a slurry of active ingredients with an acceptable vegetable oil, light liquid petrolatum or other inert oil or triglyceride.
Tablets are made by preparing a powder mixture, granulating or slugging, adding a lubricant and pressing into tablets. The powder mixture is prepared by mixing an active ingredient, suitably comminuted, with a diluent or base such as starch, lactose, kaolin, dicalcium phosphate and the like. The powder mixture can be granulated by wetting with a binder such as corn syrup, gelatin solution, methylcellulose solution or acacia mucilage and forcing through a screen. As an alternative to granulating, the powder mixture can be slugged, i.e., run through the tablet machine and the resulting imperfectly formed tablets broken into pieces (slugs). The slugs can be lubricated to prevent sticking to the tablet-forming dies by means of the addition of stearic acid, a stearic salt, talc or mineral oil. The lubricated mixture is then compressed into tablets.
Advantageously, the tablet can be provided with a protective coating consisting of a sealing coat or enteric coat of shellac, a coating of sugar and methylcellulose and polish coating of carnauba wax.
Fluid unit dosage forms for oral administration such as in syrups, elixirs and suspensions can be prepared wherein each teaspoonful of composition contains a predetermined amount of an active ingredient for administration.
The water-soluble forms can be dissolved in an aqueous vehicle together with sugar, flavoring agents and preservatives to form a syrup. An elixir is prepared by using a hydroalcoholic vehicle with suitable sweeteners together with a flavoring agent. Suspensions can be prepared of the insoluble forms with a suitable vehicle with the aid of a suspending agent such as acacia, tragacanth, methylcellulose and the like.
For parenteral administration, fluid unit dosage forms are prepared utilizing an active ingredient and a sterile vehicle, water being preferred. The active ingredient, depending on the form and concentration used, can be either suspended or dissolved in the vehicle. In preparing solutions the water-soluble active ingredient can be dissolved in water for injection and filter sterilized before filling into a suitable vial or ampule and sealing. Advantageously, adjuvants such as a local anesthetic, preservative and buffering agents can be dissolved in the vehicle. Parenteral suspensions are prepared in substantially the same manner except that an active ingredient is suspended in the vehicle instead of being dissolved and sterilization cannot be accomplished by filtration. The active ingredient can be sterilized by exposure to ethylene oxide before suspending in the sterile vehicle. Advantageously, a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the active ingredient.
In addition to oral and parenteral administration, the rectal and vaginal routes can be utilized. An active ingredient can be administered by means of a suppository. A vehicle which has a melting point at about body temperature or one that is readily soluble can be utilized. For example, cocoa butter and various polyethylene glycols (Carbowaxes) can serve as the vehicle.
For intranasal installation, a fluid unit dosage form is prepared utilizing an active ingredient and a suitable pharmaceutical vehicle, preferably P.F. water, a dry powder, can be formulated when insulation is the administration of choice.
For use as aerosols, the active ingredients can be packaged in a pressurized aerosal container together with a gaseous or liquefied propellant, for example, dichlorodifluoromethane, carbon dioxide, nitrogen, propane, and the like, with the usual adjuvants such as cosolvents and wetting agents, as may be necessary or desirable. The term “unit dosage form” as used in the specification and claims refers to physically discrete units suitable as unitary dosages for human and animal subjects, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect in association with the required pharmaceutical diluent, carrier or vehicle. The specifications for the novel unit dosage forms of this invention are dictated by and are directly dependent on (a) the unique characteristics of the active material and the particular therapeutic effect to be achieved, and (b) the limitation inherent in the art of compounding such an active material for therapeutic use in humans, as disclosed in this specification, these being features of the present invention. Examples of suitable unit dosage forms in accord with this invention are tablets, capsules, troches, suppositories, powder packets, wafers, cachets, teaspoonfuls, tablespoonfuls, dropperfuls, ampules, vials, segregated multiples of any of the foregoing, and other forms as herein described.
The active ingredients to be employed as antineoplastic and/or antimicrobial agents can be easily prepared in such unit dosage form with the employment of pharmaceutical materials which themselves are available in the art and can be prepared by established procedures. The following preparations are illustrative of the preparation of the unit dosage forms of the present invention, and not as a limitation thereof. The following are examples of several dosage forms, in which the notation “active ingredient” signifies Cribrostatin 6.
COMPOSITION “A”
Hard-Gelatin Capsules
One thousand two-piece hard gelatin capsules for oral use, each capsule containing 200 mg of an active ingredient are prepared from the following types and amounts of ingredients:
Active ingredient, micronized
20 g
Corn Starch
20 g
Talc
20 g
Magnesium stearate
2 g
The active ingredient, finely divided by means of an air micronizer, is added to the other finely powdered ingredients, mixed thoroughly and then encapsulated in the usual manner.
The foregoing capsules are useful for treating a neoplastic disease by the oral administration of one or two capsules one to four times a day.
Using the procedure above, capsules are similarly prepared containing an active ingredient in 5, 25, and 50 mg amounts by substituting 5 g, 25 g and 50 g of an active ingredient for the 20 g used above.
COMPOSITION “B”
Soft Gelatin Capsules
One-piece soft gelatin capsules for oral use, each containing 20 mg of an active ingredient, finely divided by means of an air micronizer, are prepared by first suspending the compound in 0.5 ml of corn oil to render the material capsulatable and then encapsulating in the above manner.
The foregoing capsules are useful for treating a neoplastic disease by the oral administration of one or two capsules one to four times a day.
COMPOSITION “C”
Tablets
One thousand tablets, each containing 20 mg of an active ingredient, are prepared from the following types and amounts of ingredients:
Active ingredient, micronized
20
g
Lactose
300
g
Corn starch
50
g
Magnesium stearate
4
g
Light liquid petrolatum
5
g
The active ingredient, finely divided by means of an air micronizer, is added to the other ingredients and then thoroughly mixed and slugged. The slugs are broken down by forcing them through a Number Sixteen screen. The resulting granules are then compressed into tablets, each tablet containing 20 mg of the active ingredient.
The foregoing tablets are useful for treating a neoplastic disease by the oral administration of one or two tablets one to four times a day.
Using the procedure above, tablets are similarly prepared containing an active ingredient in 25 mg and 10 mg amounts by substituting 25 g and 10 g of an active ingredient for the 20 g used above.
COMPOSITION “D”
Oral Suspension
One liter of an aqueous suspension for oral use, containing in each teaspoonful (5 ml) dose, 50 mg of an active ingredient, is prepared from the following types and amounts of ingredients:
Active ingredient, micronized
1
g
Citric acid
2
g
Benzoic acid
1
g
Sucrose
790
g
Tragacanth
5
g
Lemon Oil
2
g
Deionized water, q.s.
1000
ml
The citric acid, benzoic acid, sucrose, tragacanth and lemon oil are dispersed in sufficient water to make 850 ml of suspension. The active ingredient, finely divided by means of an air micronizer, is stirred into the syrup unit uniformly distributed. Sufficient water is added to make 1000 ml.
The composition so prepared is useful for treating a neoplastic disease at a dose of 1 teaspoonful (15 ml) three times a day.
COMPOSITION “E”
Parenteral Product
A sterile aqueous suspension for parenteral injection, containing 3 mg of an active ingredient in each milliliter for treating a neoplastic disease, is prepared from the following types and amounts of ingredients:
Active ingredient, micronized
3
g
POLYSORBATE 80
5
g
Methylparaben
2.5
g
Propylparaben
0.17
g
Water for injection, q. s.
1000
ml.
All the ingredients, except the active ingredient, are dissolved in the water and the solution sterilized by filtration. To the sterile solution is added the sterilized active ingredient, finely divided by means of an air rnicronizer, and the final suspension is filled into sterile vials and the vials sealed.
The composition so prepared is useful for treating a neoplastic disease at a dose of 1 milliliter (1 ml) three times a day.
COMPOSITION “F”
Suppository, Rectal and Vaginal
One thousand suppositories, each weighing 2.5 g and containing 20 mg of an active ingredient are prepared from the following types and amounts of ingredients:
Active ingredient, micronized
1.5
g
Propylene glycol
150
g
Polyethylene glycol #4000, q.s.
2,500
g
The active ingredient is finely divided by means of an air micronizer and added to the propylene glycol and the mixture passed through a colloid mill until uniformly dispersed. The polyethylene glycol is melted and the propylene glycol dispersion is added slowly with stirring. The suspension is poured into unchilled molds at 40° C. The composition is allowed to cool and solidify and then removed from the mold and each suppository foil wrapped.
The foregoing suppositories are inserted rectally or vaginally for treating a neoplastic disease.
COMPOSITION “G”
Intranasal Suspension
One liter of a sterile aqueous suspension for intranasal instillation, containing 2 mg of an active ingredient in each milliliter, is prepared from the following types and amounts of ingredients:
Active ingredient, micronized
1.5
g
POLYSORBATE 80
5
g
Methylparaben
2.5
g
Propylparaben
0.17
g
Deionized water, q.s.
1000
ml.
All the ingredients, except the active ingredient, are dissolved in the water and the solution sterilized by filtration. To the sterile solution is added the sterilized active ingredient, finely divided by means of an air micronizer, and the final suspension is aseptically filled into sterile containers.
The composition so prepared is useful for treating a neoplastic disease, by intranasal instillation of 0.2 to 0.5 ml given one to four times per day.
An active ingredient can also be present in the undiluted pure form for use locally about the cutis, intranasally, pharyngolaryngeally, bronchially, or orally.
COMPOSITION “H”
Powder
Five grams of an active ingredient in bulk form is finely divided by means of an air micronizer. The micronized powder is placed in a shaker-type container.
The foregoing composition is useful for treating a neoplastic disease, at localized sites by applying a powder one to four times per day.
COMPOSITION “I”
Oral Powder
One hundred grams of an active ingredient in bulk form is finely divided by means of an air micronizer. The micronized powder is divided into individual doses of 20 mg and packaged.
The foregoing powders are useful for treating a neoplastic disease, by the oral administration of one or two powders suspended in a glass of water, one to four times per day.
COMPOSITION “J”
Insufflation
One hundred grams of an active ingredient in bulk form is finely divided by means of an air micronizer. The foregoing composition is useful for treating a neoplastic disease, by the inhalation of 30 mg one to four times a day. It is of course understood that such modifications, alterations and adaptations as will readily occur to the artisan confronted with this disclosure are intended within the spirit of the present invention.
TABLE I
High Field (500 MHz) NMR Assignments for Cribrostatin
6 (3), (3,8-dimethyl-9-ethoxy-imidazo[5,1-a]isoquinoline-7,10-dione)
in CDCl 3
1 H
HMBC
GOESY
δ(mult,
13 C
j1xh = 140,
mix =
Position
J, #H)
and 15 N
jnxh = 8
COSY
.3
1
8.29s, 1H
125.68
C-3
2
3
137.64
4
5
7.90d,
124.73
C-3, C-6,
H-6
H-6,
7.5Hz, 1H
C-6a
H-11
6
7.26d,
107.73
C-6a, C-7,
H-5
7.5Hz, 1H
C-10a
6a
125.00
7
184.86
8
130.06
9
156.16
10
180.58
10a
123.49
10b
123.87
11
2.75s, 3H
12.57
C-3
H-5
12
2.06s, 3H
9.15
C-7, C-8,
C-9
13
4.40q,
69.64
C-9, C-14
H-14
6.9Hz, 2H
14
1.41t,
15.97
C-13
H-13
6.8Hz, 3H
N-4
189.5
N-2
273.9
TABLE II
Cribrostatin 6 (3) Inhibitory Activity (GI 50 , μg/ml) Against
a Panel of Human Cancer Cell Lines and Mouse Leukemia
Cell Type
Cell Line
Cribrostatin-6
Pancreas-adenocarcinoma
BXPC-3
>1
Breast-adenocarcinoma
MCF-7
0.21
CNS Glioblastoma
SF-268
0.24
Lung-NSC
NCI-H460
>1
Colon-adenocarcinoma
KM20L2
>1
Prostate
DU-145
0.38
Mouse Leukemia
P388
0.29
TABLE III
Antimicrobial Activities of Cribrostatin 6.
Minimum Inhibitory
Concentration
Microorganism
(μg/ml)
Candida albicans (ATCC 90028)
64
Cryptococcus neoformans (ATCC 90112)
2
Micrococcus luteus (Presque Isle 456)
16
Staphylococcus aureus (ATCC 29213)
16
Methicillin-resistant S. aureus
16
(clinical isolate)
Enterococcus faecalis (ATCC 29212)
32
Vancomycin-resistant E. faecalis
32
(clinical isolate)
Bacillus subtilis (clinical isolate)
2
Streptococcus pneumoniae (ATCC 6303)
0.5
Penicillin-resistant S. pneumoniae
2
(clinical isolate)
Invasive S. pneumoniae (clinical isolate)
1
Group A Streptococcus (clinical isolate)
16
Stenotrophomonas maltophilia (ATCC 13637)
>64
Escherichia coli (ATCC 25922)
>64
Enterobacter cloacae (ATCC 13047)
>64
Neisseria gonorrhoeae (ATCC 49226)
0.0625 | Cribrostatin 6, a dark blue cancer cell growth inhibiting constituent of the Republic of Maldives marine sponge Cribrochalina sp. has been isolated, and its structure (shown below) elucidated, based on a combination of RMS, high field (500 MHz, HMBC, and GOESY experiments) 15N, 1 H- and 13C NMR, and X-ray crystal structure analyses. Cribrostatin 6 also was found to inhibit the growth of a number of pathogenic bacteria and fungi. | 2 |
RELATED APPLICATIONS
This application is a continuation in part of our copending application Ser. No. 984,227, filed Nov. 30, 1992, entitled ROTATION TOOL FOR MEDICAL GUIDEWIRE and now U.S. Pat. No. 5,219,332.
BACKGROUND
1. Field of the Invention
This invention relates to a knob like tool for attachment to a medical guidewire as used, for example, to guide a catheter into an artery or arterial branch to a stenosis or partial blockage position where vessel enlargement is performed with an angioplasty balloon.
2. The Prior State of the Art
The use of guidewires in catheterization and angioplasty procedures is well known, and is further described in issued patents such as U.S. Pat. No. 4,957,117.
The guidewire is long (typically six feet or more of stainless steel wire) and slender with a relatively limber and bendable distal tip which can be angled to assist the physician in negotiating arterial curves and junctions to the desired location by fluoroscopic monitoring.
The surface of the slender guidewire is smooth and slick, and some kind of auxiliary gripping surface is needed to enable the wire to be advanced into or retracted from the arterial vessels, and especially to enable twisting or torquing rotation of the wire as needed to reorient the angled distal tip. Existing partial solutions to this need include pin-vise grips.
A pin-vise is a device that is well known in the art and which comprises a structure like a small drill chuck with a cylindrical handle. The chuck is threaded over the proximal end of the long guidewire and advanced to a desired position. A chuck collet, a part of the pin-vise, can then be tightened onto the wire so that the pin vise is firmly attached to the guidewire, and thereafter serves as a grip to facilitate manual rotation of the guidewire and/or longitudinal advancement of the same.
One of the problems which has been experienced in the art using pin-vise type grips is that they must be threaded onto the guidewire at the proximal end. This is time consuming and inconvenient because of the length of the guidewire. Thus, other types of gripping devices have been devised which attempt to overcome this problem.
One such gripping device is illustrated, for example, in U.S. Pat. No. 4,829,999. This device is constructed with a cylindrical body which has a longitudinal slit and which is spring-actuated so that by pressing two handles together which are provided on the body of the device, the longitudinal slit can be opened and placed onto the guidewire. When the handles are released, the resilient or spring-action of the cylindrical body clamps the guidewire within the longitudinal slit, much like clamping a clothespin into a clothesline.
This device overcomes the problem of having to thread the device onto the proximal end of the guidewire, but suffers from other disadvantages. For example, the handles which are located on the side of the cylindrical body may get in the way of rotational manipulation of the device. Furthermore, it is typically necessary to reposition a gripping device on a guidewire as the guidewire is advanced further into the vessels. Thus, the side mount type gripping device as described for example in the above referenced patent requires that the device be taken off and repositioned on the guidewire. If the device is dropped while taking it off, it becomes unsterile and must be replaced.
Another device which has attempted to address the problems in the art is illustrated, for example, in U.S. Pat. No. 4,858,810. This device utilizes a pin-vise constructed from two parts assembled together to provide a gripping handle for a guidewire. The device has an elongated cylindrical body which is slotted along the length to receive the guidewire, and also has a sliding mechanism which fits within the slot and which, when pushed forward, tightens down upon the guidewire in order to secure the gripping device to the guidewire for purposes of manipulation. As in the case of the spring actuated type gripping device described above, this device is also a side-mount type device, which eliminates the need for threading the device onto the proximal end of the guidewire. However, the placement of the device onto the guidewire is somewhat cumbersome and if the cylindrical body member is inadvertently dropped before the slide mechanism is placed into the longitudinal slot, once again the device may become unsterile. Another example of a device that utilizes a slide mechanism is that described in U.S. Pat. No. 5,159,861.
Still a further device which is known in the art is a side loading type of gripping device which, once again, employs a longitudinal slot along the length of the device, and which includes two cylindrical members that are threaded together. The distal end of one of the cylindrical members is formed with a plurality of fingers so that as the two members are threaded together the fingers clamp down and grip the guidewire. This device, like the others, partially solves some of the problems experienced in the art, but is otherwise more complicated in its construction and cumbersome to operate than is desirable.
SUMMARY AND OBJECTS OF THE INVENTION
The rotation tool of this invention overcomes the above and other problems in the art, and enables quick and simple lateral or sideways attachment at any desired position along a guidewire. The tool further provides two gripping modes, one in which the guidewire is captive within the tool, so that the tool cannot fall off the guidewire, but the guidewire is otherwise not longitudinally or rotationally secured to the tool so that relative movement of the tool on the guidewire is permitted. The second gripping mode is one in which the guidewire is secured to the rotation tool, both longitudinally and rotationally so that the rotation tool can be used either to advance the guidewire or to rotationally orient the guidewire to effect steering of the distal end of the guidewire.
In one presently preferred embodiment of the invention, the rotation tool is comprised of a tubular housing that is formed from two cylindrical members that are adapted to fit together in a telescoping arrangement. The two members are provided with a passageway that runs through the length of each member. A slot also runs the length of each member and extends from an outer surface of each member to the passageway running therethrough. An elastomeric gripping and retention member has one end anchored in one of the cylindrical members and the other end anchored in the other cylindrical member at the ends of the passageways formed through the cylindrical members. An elongated body of the elastomeric member is situated in the passageway running between the two ends.
The guidewire is placed into the longitudinal slot and the two cylindrical members can then be rotated relative to each other to a first position which locks the guidewire within the device, but without securing the guidewire to the device. In this position, the rotation tool or device of the present invention is in the first gripping mode described above. The cylindrical members can then be rotated to a second position which causes the elastomeric member to twist around the guidewire, but without bending the guidewire. When locked in this second position, the rotation tool or device of the present invention is in the second gripping mode described above.
A groove and retention pin or locking ring serve to irreversibly secure the two cylindrical members together once they have been assembled with the elastomeric member. This prevents the cylindrical members from being pulled apart and rotated in the wrong direction with respect to each other, thus preventing the tool from becoming entangled with and stuck to the guidewire.
It is therefore an object of the present invention to provide a rotation tool for attachment to a guidewire which overcomes the above and other problems which have been experienced in the present state of the art.
More specifically, it is an object of the present invention to provide a rotation tool for attachment to a medical guidewire which is simple and inexpensive in its construction and assembly, and which can be positioned onto a guidewire at any point along the length of the guidewire so as to eliminate the necessity for threading the tool onto the proximal end of the guidewire.
Yet a further object of the present invention is to provide a rotation tool for attachment to a medical guidewire which provides for two gripping modes, one in which the device is locked onto the guidewire but can be moved relative to the guidewire so that the guidewire is not longitudinally or rotationally gripped by the device, but the device is nonetheless prevented from falling off of the guidewire, and a second gripping mode in which the device is locked to the guidewire both longitudinally and rotationally to permit the guidewire to be steered at its distal end by manipulation of the tool.
Still a further object of the present invention is to prevent improper rotation of a rotation tool relative to a guidewire, so as to prevent it from becoming entangled with and stuck to the guidewire.
These and other objects and features of the present invention will become more fully understood from reference to the accompanying drawings which are briefly summarized below and which are used to illustrate one presently preferred embodiment of the invention in its presently understood best mode for making and using the same.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1 and 2 are exploded pictorial views showing a pair of tubular members and an elastomeric retainer which comprise a preferred embodiment of this invention;
FIG. 3 is a side elevation of a first tubular member;
FIG. 4 is a top view of the first tubular member shown in FIG. 3;
FIG. 5 is an end view of one end of the first tubular member shown in FIG. 3;
FIG. 6 is an opposite end view of the first tubular member of FIG. 3;
FIG. 7 is a sectional side elevation on line 7--7 of FIG. 6;
FIG. 8 is a sectional side elevation on line 8--8 of FIG. 6;
FIG. 9 is an enlarged partial sectional view on line 9--9 of FIG. 6 and showing a detent seat;
FIG. 10 is a side elevation of a second tubular member;
FIG. 11 is an end view of one end of the second tubular member of FIG. 10;
FIG. 12 is an opposite end view of the second tubular member;
FIG. 13 is a sectional side elevation showing the first and second tubular members as assembled together;
FIG. 14 is a pictorial view of the engaged tubular members, and showing the elastomeric member in a stretched position ready for installation;
FIG. 15 shows the partially installed elastomeric member;
FIG. 16 shows the completely assembled tool with a guidewire in an initial position;
FIG. 17 shows the tubular members rotated to a first position which makes the guidewire captive, but longitudinally and rotationally free within the tool;
FIG. 18 is a longitudinal cross sectional view taken on line 18--18 of FIG. 17, and more particularly shows the relationship between the elastomeric member and the guidewire when the tubular members are rotated to the first position;
FIG. 19 is a cross sectional view taken on line 19--19 of FIG. 17 further showing the relationship between the elastomeric member and the guidewire when the tubular members are rotated into the first position;
FIG. 20 shows the tubular members from a different angle, and rotated to a locked position in which the guidewire is longitudinally and rotationally secured relative to the tool;
FIG. 21 is a sectional side elevation taken on line 21--21 of FIG. 20, and more particularly showing the relationship of the elastomeric member and the guidewire when the first and second tubular members are rotated to the second position;
FIG. 22 is a perspective view with portions broken away to further illustrate the relationship between the elastomeric member and guidewire when the first and second tubular members are rotated to the second position; and
FIG. 23 is a sectional view taken on line 23--23 of FIG. 20 which further illustrates the relationship between the guidewire and the elastomeric member when the first and second tubular members are rotated to the second position; and
FIGS. 24 and 25 are exploded perspective views illustrating alternative ways of securing the first and second tubular members together after assembly to prevent them from being pulled apart and rotated the wrong way relative to one another.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
The components of a rotation tool or gripping-knob assembly 10 are shown in exploded view in FIGS. 1 and 2. The components are a first tubular plug member generally designated at 11, a mating second tubular socket member generally designated at 12, and an elastomeric retainer generally designated at 13. The steps of assembling the tool are shown in FIG. 14-15, and the assembled tool is shown as placed over and engaged with a medical guidewire 14 in FIGS. 16-23. The details of each component will first be described, and subsequently the assembly and use of the tool.
Referring to FIGS. 1-9, a first tubular member 11 has a cylindrical head 16, a coaxial cylindrical shank 17 extending from the head, a head end surface 18, and a shank end surface 19. The shank has a slightly reduced diameter as compared to the head, and the respective diameters are typically about 0.455 inch and 0.352 inch. An annular shoulder 20 is defined at the junction of the head 16 and shank 17.
A rectangular-in-cross-section recess 22 extends into head 16 from end surface 18 part way toward shoulder 20. As shown best in FIGS. 3-6, a cylindrical bore or passageway 23 extends from a base 24 of recess 22 to shank end surface 19. Passageway 23 has a typical diameter of 0.12 inch, and an axial centerline which is parallel to, but offset by slightly less than the radius of the passageway 23 from the axial centerline of the head 16 and shank 17.
A slot 26 (shown best in FIGS. 1-2 and 5-6) extends from recess 22 and passageway 23 radially outwardly to the outer surfaces of the head 16 and shank 17, and extends the full length of member 11 between end surfaces 18 and 19. A semiconical recess 27 (FIGS. 3 and 5) is concentric with the head 16 and shank 17, and converges from end surface 19 to terminate at passageway 23 adjacent shoulder 20. Recess 27 is formed in only one inner side of the shank 17, and the nearly semicircular outer perimeter of the recess 27 extends from a sidewall of slot 26 to terminate at a point of tangency 21 with the lower (as seen in FIG. 5-6) perimeter of passageway 23.
An extension protrudes from shank end surface 19 to define a stop 29 with a shoulder 30 (see FIG. 3) extending from passageway 23 to the outer surface of cylindrical shank 17. As hereinafter more fully described, stop 29 helps to assure that rotation of first tubular member 11 relative to second tubular member 12 will occur in the proper direction indicated by arrows 36. The stop 29 has a chamfered surface 31 adjacent slot 26 as best seen in FIGS. 2 and 4. A teardrop-shaped detent seat 33 is formed as a depression in end surface 19 below shoulder 30 (as shown in FIGS. 2, 6 and 9) and adjacent the perimeter of shank 17. A preferred cross-sectional shape of seat 33 is shown in FIG. 9, and the blunt end of the seat 33 is positioned about 54 degrees counterclockwise from the six o'clock position in FIG. 6.
The outer surface of cylindrical head 16 has a knurled portion 34 (FIGS. 1-2) for secure gripping, and a smooth portion 35 surrounding recess 22. The smooth portion 35 is embossed with arrows 36 designating the proper rotation direction to turn plug member 11 to engage assembly 10 with guidewire 14 as explained below in greater detail.
Tubular socket member 12 is shown in detail in FIGS. 1-2 and 10-13, and is generally cylindrical in shape with first and second ends 39 and 47. A coaxial cylindrical bore 40 extends from first end 39 to a base surface 42 (see FIG. 10) axially spaced from the second end 47. Bore 40 is dimensioned to receive shank 17 of the tubular plug member 11 in rotatable engagement, and has a typical inside diameter of 0.356 inch for a shank outside diameter of 0.352 inch. An off-axis cylindrical bore or passageway 43 (FIGS. 10-11) extends from surface 42 to a rectangular recess 44 which is identical to recess 22. The recess 44 has a base 45, and extends axially to second end 47.
A slot 52 is formed in socket member 12 between ends 39 and 47, and extends from the outer surface of the member radially inward to bore 40, passageway 43 and recess 44. A detent pin 48 extends from base surface 42, and is positioned adjacent the inner surface of bore 40, passageway 43 and recess 44. The detent pin 48 is positioned adjacent the inner surface of bore 40 about 110 degrees counterclockwise from the twelve o'clock position in FIG. 11. The pin 48 is preferably integrally formed with member 12, and is slightly tapered for molding convenience, and for structural strength at the pin base.
Referring to FIGS. 1-2, the outer surface of member 12 has a knurled gripping portion 49, and a smooth portion 50 in which are embossed a pair of first and second position markers 51 and 57 (the latter is shown in FIG. 20). When members 11 and 12 are engaged, markers 51 and 57 are alternatively aligned with slot 26 of the plug member 11 in the several operational positions of the assembly as described below.
Elastomer retainer 13 is best seen in FIGS. 1-2 and 14-15, and is an integral member having enlarged circular heads 55 at its opposite ends. Heads 55 are dimensioned to seat securely in recesses 22 and 44 when assembled with plug and socket members 11 and 12. The heads 55 are connected by a body member 56 which is rectangular in cross section. The body member 56 is intended to fill a substantial portion of passageways 23 and 43 when assembled with the plug and socket members. For example, if the passageways 23 and 43 have matching diameters of about 0.12 inch, the cross-sectional dimensions of body member 56 are preferably about 0.10 and 0.15 inch.
Retainer 13 is preferably molded from neoprene or silicone rubber with a Shore A hardness of about 55. Plug and socket members 11 and 12 are preferably each integrally injection molded for economy and production convenience, and a suitable material is ABS plastic.
The assembly of the several components just described is shown in FIGS. 13 15. As shown best in FIG. 13, the shank 17 of plug member 11 is inserted into bore 40 of the socket member 12 until the end 19 of shank 17 abuts against pin 48. Radial slots 26 and 52 are in alignment as shown in FIG. 14.
Body member 56 is then tensioned to elongate retainer 13 as shown in FIG. 14, and the body member 56 is fitted into aligned slots 26 and 52 to seat one of retainer heads 55 in rectangular recess 22 of the plug member 11 (FIG. 15). The still-elongated body member 56 is then fully fitted through slots 26 and 52 into passages 23 and 43, and the second head 55 is seated in recess 44 of the socket member 12. In this fully assembled condition, body member 56 remains under substantial tension, and the resulting restoring force urges the plug and socket members 11 and 12 together.
Initial engagement of the device 10 over guidewire 14 is illustrated in FIG. 16. The device is simply moved laterally over the guidewire 14 which passes through aligned slots 26 and 52 to rest against retainer 13. Plug member 11 is then rotated about 25 degrees in the direction of arrows 36 to an intermediate position (FIGS. 17-19) in which detent pin 48 moves into seat 33. As noted above, stop 29 helps to assure that rotation will occur only in the direction of arrows 36, since stop 29 will prevent rotation in the other direction due to engagement of detent pin 48, when shank 17 is adequately seated in bore 40. Because of the tension exerted by retainer 13, the seating of the pin 48 into seat 33 occurs with a click so as to give an audible and a tactile signal that the intermediate position has been reached, and visual confirmation is also provided by the alignment of slot 26 with first position markers 51. As shown best in FIGS. 18-19, in the intermediate position, the guidewire 14 is captive within the shank 17 of socket member 11 by the misalignment of slots 26 and 52, but is not secured by the body member 56 of retainer 13, which is only slightly twisted in this position, thus device 10, permitting longitudinal repositioning of the device along the guidewire 14 without having to remove it from guidewire 14.
To lock the device 10 to the guidewire 14 both longitudinally and rotationally, the plug and socket members 11 and 12 are lightly separated against the force of the tensioned retainer 13 to move detent pin 48 out of seat 33. The plug member is then rotated in the direction of arrows 36 by about 225 degrees to the final position as shown in FIGS. 20-23. Pin 48 rides along shank end surface 19 during this rotational movement, and provides a tactile signal of reaching the final position, again due to the tension exerted by retainer 13, by dropping into the shank end of radial slot 26. Visual confirmation of this position is provided by the alignment of slot 26 with second position marker 52, and further rotation is discouraged by stop 29.
Relative rotation of the plug and socket members 11 and 12 to this position twists the retainer 13 within the passageways 23, 27 and 43, and the guidewire 14 is thus gripped and secured by the body member 56 as it twists about guidewire 14. The semiconical recess 27 (see FIGS. 3 and 6) provides space for the body member 56 of retainer 13 to be twisted up and around guidewire 14, without bending the guidewire. Importantly, guidewire 14 is not bent so that rotation of device 10 results in a corresponding rotation at the distal end of guidewire 14 in the vessel. The conical passageway 27 in shank 17 permits the body member 56 of retainer 13 to twist up and around guidewire 14 to securely grip it. This is shown best in FIGS. 21-23. Guidewire 14 is thus now secured by device 10 to permit both longitudinal and/or rotational manipulation of guidewire 14 by manipulating the tool or device 10.
The central axis of passageways 23 and 43 are intentionally spaced from the common rotation axis of the plug and socket members to insure that after body member 56 is seated in passageways 23 and 43, the guidewire will come to rest on body member 56 (see FIGS. 18 and 19) in substantial alignment with the common rotation axis. This feature avoids the undesirable result of the guidewire extending from the assembly at an angle or off-centered axis which would result in inconvenient operation.
The design of the device permits quick and simple lateral or sideways installation at any position along the guidewire 14, and the rotational alignment of the plug and socket members 11 and 12 is easily determined either visually or by tactile feel when the detent pin 48 moves into a partially or fully retained position. Should it be necessary to reposition the assembly during advancement of the guidewire 14 into an artery, the plug and socket members 11 and 12 are simply rotated from the final or locked position back to the intermediate position. When a new position along the guidewire is established, the members 11 and 12 are returned to the locked position in which the device provides secure gripping of the guidewire 14 for both longitudinal and rotational movement.
It has been found that in practice, not withstanding the tension exerted by the elastomeric retainer 13, it may be possible to pull the tubular members 11 and 12 far enough apart that the detent pin 48 may be pulled clear of the stop 29 thus permitting the tubular members 11 and 12 to be rotated in the wrong direction, in other words in the direction opposite to that shown by the arrows 36. When this happens, the guidewire 14 may become entangled in the elastomeric retainer 13 as the two tubular members 11 and 12 are rotated in the wrong direction so that the rotation tool 10 becomes completely entangled and stuck to the guidewire 14. This of course is an undesirable result. Accordingly, in another aspect of the invention, to assure that this cannot happen, the rotation tool 10 may be provided with a means for irreversibly securing the two tubular members 11 and 12 together after they are assembled so that they cannot be pulled far enough apart to permit the detent pin 48 to rotate past the stop 29 in the wrong direction.
By way of example, FIGS. 24 and 25 illustrate two ways in which this may be accomplished. In FIG. 24, tubular member 11 is illustrated as having a circular groove 60 which is formed in the shank 17. The tubular socket member 12 on the other hand is provided with a small bore 62 which extends through the tubular socket member 12. A retainer pin 64 is adapted to be inserted through the bore 62 after the rotation tool had been completely assembled as described above. When the retainer pin 64 is inserted through bore 62, the end of the retainer pin 64 engages the circular groove 60. This prevents the tubular socket member 12 from being able to be pulled far enough apart with respect to tubular member 11 that the detent pin 48 can be rotated in the wrong direction past the stop 29 on shank 17. However, the circular groove 60 is wide enough to allow a limited amount of separation between the two members 11 and 12, in order to permit the detent pin 48 to be easily disengaged from the teardrop shaped seat 33 when rotating the tool into the final position as previously described.
FIG. 25 illustrates an alternative way of irreversibly securing the two tubular members 11 and 12 together after assembly. In the embodiment of FIG. 25, the groove 60 is the same but instead of the retention pin 64, the tubular members 11 and 12 are irreversibly secured together by a snap ring 66 which is placed inside the bore 40 of the tubular socket member 12. The snap ring 66 is sized so that the tubular socket member 12 can be snapped on the shank 17 and once the snap ring 66 drops into the groove 60, the tubular members 11 and 12 will only be permitted to be pulled apart to a limited degree. This preventing the tubular members 11 and 12 from being rotated relative to one another in the wrong direction or in other words in the direction counter to arrows 36. The width of snap ring 66 is somewhat smaller than the width of the groove 60 to permit the tubular members 11 and 12 to be pulled apart slightly in order to permit the detent pin 48 to be easily unseated from the tear dropped shaped seat 33 in the same manner as described in connection with the embodiment of FIG. 24.
The invention may be embodied in other specific forms without departing from its spirit or essential characteristics. The described embodiments are to be considered in all respects only as illustrative and not restrictive. The scope of the invention is, therefore, 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 to be embraced within their scope. | A gripping-knob rotation tool for attachment to a medical guidewire as used in angioplasty and other medical procedures. The tool is installed laterally over the guidewire at any desired position along the length of the wire, and is secured thereto by a simple rotational or twisting motion. The tool provides a convenient gripping surface during rotation or translational movement of the guidewire, and is adjustable for repositioning along the length of the wire after initial engagement. | 0 |
FIELD OF THE INVENTION
[0001] The present invention generally relates to the field of article feed mechanisms and sorters and more particularly to inline vibratory parts feeders.
BACKGROUND OF THE INVENTION
[0002] Vibratory parts feeders are commonly known apparati for providing oriented parts from a mass of disoriented parts or for transporting parts along a processing path. In providing oriented parts, vibratory parts feeders typically include a vibratory bowl which is driven by a vibratory drive unit. The bowl is intregally configured typically with a helicon oriented path to transport the parts under vibratory action to a bowl exit location near the top of the bowl.
[0003] There are a number of problems with this conventional technology including limitation to the parts per minute that can be delivered by vibratory bowl apparati, part jams which often need to be cleared manually by an operator and typically high operating and installation costs of vibratory bowl feeders.
PRIOR ART
[0004] A number of prior patents have been issued by the United States Patent Office in regard to vibratory parts feeder, a good example of this is U.S. Pat. No. 5,630,497 by Graham patented May 20, 1997 entitled Vibratory Parts Feeder with Pivotal Top Confinement. This patent reviews the state of the art of vibratory bowl feeders and the problems encountered with them.
[0005] Due to the high capital cost required for the manufacture and purchase of vibratory bowl feeders, inherent jamming problems and requirement of constant supervision by an operator to clear jams as they occur and their low output or productivity despite the high cost of producing the machinery.
[0006] Therefore, this is a need for a new and improved method of providing oriented parts from a mass of disoriented parts which provides for a reliable low cost method for delivering oriented parts for subsequent operations.
SUMMARY OF THE INVENTION
[0007] The present invention an inline feeder for delivering oriented parts comprises:
[0008] a) a means for storing and transporting and also a means for presenting parts onto a vibratory linear feeder;
[0009] b) a means for sensing flow and orientation of said parts on said linear feeder; and
[0010] c) a means for rejecting misoriented or jammed parts from said linear feeder and allowing properly oriented parts to be delivered.
[0011] Preferably wherein said rejecting means includes a tooling plate having a part profile allowing only substantially correctly oriented parts to pass there through.
[0012] Preferably wherein said sensing means includes a second part sensor for sensing flow of parts along said linear feeder, said flow sensor operable and communicating with said rejecting means such that when flow is not satisfactory parts are rejected.
[0013] Preferably wherein said rejected parts are returned to said storing and transporting means.
[0014] Preferably wherein said sensing means includes a third part sensor for sensing proximity of parts passing through said tooling plate operably communicating with said second flow sensor for monitoring flow of parts through said tooling plate and further communicating with said rejecting means such that when flow is not satisfactory parts are rejected
[0015] Preferably wherein said sensing means includes a first part sensor for sensing the load of parts moving along said linear feeder, said first part sensor operatively communicating with said transporting means for increasing or decreasing part loading on said linear feeder as required to maintain a predetermined load.
[0016] Preferably wherein said second part sensor being disposed proximate a clearing station located just prior to parts entering the tooling plate.
[0017] Preferably wherein the rejecting means includes an air fitting/valve for applying a burst of compressed gas against a part for removing said part from said linear feeder, wherein said air valve operably in communication with said sensing means for triggering a part rejection.
[0018] Preferably wherein said transporting means includes a hopper section including a vibratory hopper for storing parts and transporting parts to said presenting means.
[0019] Preferably wherein said presenting means includes an elevator section including an inclined elevator for receiving parts from said vibratory hopper and depositing said parts onto said linear feeder.
[0020] Preferably wherein said sensing means includes a first part sensor for sensing the load of parts moving along said linear feeder, said first part sensor operatively communicating with said inclined elevator for increasing or decreasing part loading on said linear feeder by increasing or decreasing the number of parts delivered by said inclined elevator.
[0021] Preferably wherein the vibratory hopper and the linear feeder, urge or transport parts in opposing directions.
[0022] Preferably wherein said inline feeder further includes a means for clearing jams in said tooling plate operably in communication with said sensing means for.
[0023] Preferably wherein said clearing means includes a pneumatic slide for opening said tooling plate for clearing jams.
[0024] Preferably wherein said tooling plate includes an upper plate position above and adjacent to a lower plate wherein said upper and lower plate define a part profile wherein said tooling plate can be opened by separating said upper plate from said lower plate.
[0025] The present invention is also a method of operating an inline feeder used for delivering oriented parts comprising the steps of:
[0026] (a) storing parts in vibratory hopper;
[0027] (b) delivering said parts to an inclined elevator;
[0028] (c) elevating and delivering said parts to a linear feeder;
[0029] (d) sensing excessive part load on linear feeder;
[0030] (e) reducing part loading by reducing elevator stroke or frequency; and
[0031] (f) feeding parts through an intelligent tooling plate which allows only substantially correctly oriented parts to pass there through
[0032] Preferably a method of operating an inline feeder used for delivering oriented parts comprising the steps of:
[0033] (a) storing parts in a hopper;
[0034] (b) delivering said parts to an elevator;
[0035] (c) elevating and delivering said parts to a linear feeder;
[0036] (d) sensing and clearing misoriented or jammed parts from a linear feeder prior to entering tooling plate;
[0037] (e) feeding said parts through an intelligent tooling plate.
[0038] Preferably a method of operating an inline feeder used for delivering oriented parts comprising the steps of:
[0039] (a) storing parts in a hopper;
[0040] (b) delivering said parts to an elevator;
[0041] (c) elevating and delivering said parts to a linear feeder;
[0042] (d) sensing excessive part load on linear feeder;
[0043] (e) reducing part load by reducing elevator stroke or frequency;
[0044] (f) sensing misoriented parts at clearing station;
[0045] (g) clearing misoriented or jammed parts using compressed air from linear feeder at clearing station;
[0046] (h) feeding correctly oriented parts through an intelligent tooling plate.
BRIEF DESCRIPTION OF THE DRAWINGS
[0047] [0047]FIG. 1 is a schematic front perspective view of the current invention an Inline Feeder;
[0048] [0048]FIG. 2 is a schematic back perspective view of the current invention the Inline Feeder;
[0049] [0049]FIG. 3 is a schematic cross-sectional view of the tooling plate of the Inline Feeder;
[0050] [0050]FIG. 4 is a flow diagram showing the method of operating the Inline Feeder;
[0051] [0051]FIG. 5 is a flow diagram showing the method of operating the Inline Feeder;
[0052] [0052]FIG. 6 is a flow diagram showing the method of operation of the Inline Feeder;
[0053] [0053]FIG. 7 is a flow diagram showing the method of operating the Inline Feeder;
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0054] The present invention an Inline Feeder shown generally as 30 is comprised of the following major components, namely hopper section shown generally as 31 , elevator section shown generally as 35 and inline vibratory feeder section shown generally as 33 . These sections are all mounted onto base 50 as shown.
[0055] Hopper Section
[0056] Hopper section shown generally as 31 includes a vibratory hopper 32 which is a rectangularly box shaped receptacle for receiving parts 40 therein. Vibratory hopper 32 is mounted onto a hopper vibratory drive 34 which in turn is mounted onto base 50 . Hopper vibratory drive 34 is the type known in the industry which operates at a frequency of approximately 3,600 (three thousand, six hundred) vibrations per minute and vibratory hopper 32 is arranged in such a manner that parts 40 flow normally in direction 36 as shown in FIG. 1. Vibratory hopper 32 is charged with parts 40 via traditional charging methods and also receives rejected parts 42 which slide down ramp 44 . Parts 40 make their way to elevator accumulator 48 waiting to be moved by elevator section shown generally as 35 .
[0057] Elevator Section
[0058] Elevator Section 35 includes an inclined elevator which has a more or less rectangular cross section and is mounted slidably onto elevator guides 54 which are mounted on an inclined angle 60 relative to base 50 . Elevator pneumatic piston 56 operates functionally to move inclined pneumatic slide elevator 52 upwardly and downwardly in elevator direction shown as 58 . Parts 40 in elevator accumulator 48 are raised by inclined pneumatic slide elevator 52 moving in an upward direction 58 until parts 40 slide off of the top surface of inclined pneumatic slide elevator 52 and onto part receiving platform 64 . The stroke of incline pneumatic slide elevator 52 can be functionally controlled by first part sensor 66 which determines the load of parts 40 on linear feeder 70 . When first part sensor 66 detects a shortage of parts on linear feeder 70 as well on part receiving platform 64 , the stroke or frequency of incline pneumatic slide elevator 52 is increased to discharge more parts onto part receiving platform 64 . Conversely if too many parts are detected on part receiving platform 64 and linear feeder 70 , the stroke or frequency of incline pneumatic slide elevator 52 is decreased thereby depositing fewer parts onto part receiving platform 64 . Fist part sensor is preferably a background suppression type sensor available from Baumer Inc.
[0059] Parts 40 are continually being vibratorily fed by vibratory hopper 32 onto elevator accumulator portion 48 such that parts 40 are continuously available at elevator accumulator 48 for transport of parts 40 to part receiving platform 64 . First part sensor 66 control the stroke or frequency of incline pneumatic slide elevator 52 thereby controlling the number of parts on part receiving platform 64 and linear feeder 70 .
[0060] Inline Vibratory Feeder Section
[0061] Inline vibratory feeder section shown generally as 33 is comprised of a linear feeder 70 which is mounted onto an inline feeder vibratory drive 72 which in turn is mounted onto a base 50 . Inline feeder vibratory drive 72 is the type generally known in the industry which operate at approximately 3,600 (three thousand six hundred) vibrations per minute. These type of inline vibratory drives allow one to adjust the speed of parts moving along the inline feeder by for example adjusting the amplitude of the inline feeder. Parts 40 moving along linear feeder 70 come to clearing station 80 just prior to entering tooling plate 82 . At clearing station 80 , a second part sensor 84 senses the flow of parts at the clearing station including the dwell time of a part at the clearing station. Second part sensor 84 preferably is a flow sensor mounted adjacent or just above clearing station 80 . Flow sensor 84 can be of the background suppression type currently available through Baumer Inc., or any other sensor that may be suitable. Depending upon whether there is jam at clearing station 80 or there are too many parts, or parts are not travelling through the tooling plate 82 , second part sensor 84 may trigger air fitting/valve 86 which rejects parts and clears them from clearing station 80 . Rejected parts 42 under air pressure are pushed down ramp 44 and into vibratory hopper 32 to once again be fed through the cycle. Parts 40 oriented the right way will enter through tooling plate 82 . Only correctly oriented parts enter tooling plate 82 successfully. Should a part be misoriented or should double parts be present or should there be jams or misorientations of any kind, tooling plate 82 will not allow the parts to pass there through. In addition, a third part sensor behind tooling plate 82 determines the time a part 40 has taken to travel from clearing station 80 to third part sensor 90 . When a preset dwell time is exceeded, tooling plate 82 is completely opened up by a pneumatic cylinder thereby clearing any jams within tooling plate 82 . Parts that are correctly oriented and move through tooling plate 82 in a predetermined amount of time are discharged at part discharge 46 and moved onto subsequent assembly operations not included in this patent.
[0062] Tooling Plate
[0063] Referring now to FIG. 3 showing generally in cross sectional view a tooling plate as 82 . Tooling plate 82 includes upper plate 92 , lower plate 94 , a part profile 96 and a part 40 passing there through. By way of example only the part shown is coined shaped having bevelled edges. Therefore should the part lay on one side, the bevelled edges will conform to the part profile 96 and the part will pass through tooling plate 82 . On the other hand, if part 40 is reversely oriented (upside down), the bevelled edges will not register with part profile 96 thereby preventing parts 40 from passing through tooling plate 82 . In this manner misoriented parts are prevented from passing through tooling plate 82 . Only parts which pass through tooling plate 82 eventually become usable parts and are discharged at part discharge 46 and on the further assembly operations. Upper plate 92 can be pivotally moved away from lower plate 94 through pneumatic cylinders not shown. Pivoting upper plate 92 or opening tooling plate 82 may be necessary to clear jams. It is understood that part profile 96 is just one example of a myriad of part shapes that can be accommodated.
[0064] In addition to second part sensor 84 a third part sensor 90 which preferably is a proximity sensor is mounted adjacent or just above tooling plate 82 . Preferably third part sensor 90 sees through an aperture (not shown) in upper plate 92 in order to “see” or sense parts travelling through tooling plate 82 . Second part sensor 84 and third part sensor 90 communicate logically with each other to determine if any jam condition exists. In addition should a jam occur within tooling plate 82 itself for example if two parts are nested together and manage to enter into tooling plate 82 then second part sensor 84 together with third part sensor 90 will recognize this condition and open up tooling plate 82 by lifting off upper plate 92 from lower plate 94 . The second part sensor 84 together with the third part sensor 90 provide an intelligent clearing system which automatically clears almost all jams that could occur.
[0065] In Use
[0066] In use inline feeder 30 operates as follows:
[0067] Vibratory hopper 32 is charged with parts 40 , either from an external source not shown by means conventionally such as chutes, part hoppers, conveyor belts etc. Vibratory hopper 32 also receives parts that have been rejected from the linear feeder 70 section thereby finding there way back into vibratory hopper 32 . Vibratory hopper 32 is mounted onto hopper vibratory drive 34 which in turn is mounted to base 50 . Vibratory hopper 32 via vibratory drive 34 urges parts 40 along direction 36 until elevator accumulator 48 is filled with parts 40 . The size and shape of vibratory hopper 32 is can be altered to accommodate parts of different sizes and shapes. Normally speaking the larger the parts the larger the hopper required and in turn the entire unit would be scaled larger to accommodate a larger part. Parts 40 shown in the drawings are by way of example only. Parts 40 shown are a coined shaped part being relatively flat and having bevelled and/or chamfered ends.
[0068] Once parts 40 are delivered to elevator accumulator 48 , incline pneumatic slide elevator 52 is moved upwardly shown as direction 58 along elevator guides 54 thereby elevating parts up to part receiving platform 64 . Once inclined pneumatic slide elevator 52 has reached a high enough position, parts 40 will slide and/or tumble onto part receiving platform 64 under gravity. A first part sensor 66 senses the load on part receiving platform as well as linear feeder 70 and controls the frequency as well as the stroke of the inclined pneumatic slide elevator 52 . Inclined pneumatic slide elevator 52 is preferably operated by an elevator pneumatic piston 56 and is inclined at an angle of around 60 degrees shown as angle theta 60 in the diagram. When first part sensor 66 determines that more parts are required, it sends a single to increase the stroke or increase the frequency of inclined pneumatic slide elevator 52 such that more parts are delivered onto part receiving platform 64 . Should fewer parts be required such as when first part sensor 66 determines an overload of part receiving platform 64 the stroke and/or the frequency of inclined pneumatic slide elevator 52 is reduced thereby delivering fewer parts to part receiving platform 64 . Linear feeder 70 is mounted onto a separate inline feeder vibratory drive 72 which is mounted onto base 50 . Inline feeder vibratory drive 72 moves parts 40 along inline feeder in a linear fashion until they arrive at clearing station 80 . At clearing station 80 , second part sensor 84 determines the dwell time of part 40 at clearing station 80 , and also determines whether or not there is a build up or a jam of parts at clearing station 80 . Should parts 40 not be moving past clearing station 80 at a predetermined pass time, second parts sensor 84 will send a signal to air fitting/valve 86 thereby forcibly with air pressure rejecting parts 42 which are fed down ramp 44 and back into vibratory hopper 32 . Parts 40 which are properly oriented enter tooling plate 82 and are monitored by a third part sensor 90 which is logically interfaced with second parts sensor 84 to determine the rate at which parts move from clearing station 80 through tooling plate 82 .
[0069] By way of example only, if parts 40 are not passing through tooling plate 82 at a fast enough rate as measured by second part sensor 84 and third part sensor 90 , a signal is sent to open up tooling plate 82 which is done by a pneumatic slide not shown wherein upper plate 92 is pivoted away from lower plate 94 thereby clearing parts 40 out of tooling plate 82 .
[0070] Those skilled in the art will see that the linear feeder 70 section is totally automated and intelligent in that part loading is monitored, misoriented parts and/or jams are automatically cleared at clearing station 80 , and should some parts become jammed within tooling plate 82 itself, a third sensor is in place to detect that condition and clearing of tooling plate 82 will automatically take place normally by pivoting open upper plate 92 from lower plate 94 .
[0071] Correctly oriented parts arriving at clearing station 80 move easily and quickly through tooling plate 82 and outward through part discharge 46 where correctly oriented parts are then subsequently fed to other assembly operations.
[0072] A minimal amount of operator assistance is required with this set up in that, first part sensor 66 , second part sensor 84 and third part sensor 90 provide an intelligent clearing system which is able to detect almost all jams or misorientation of parts and automatically clear these misorientations and/or jams without operator interference.
[0073] Method of Operation
[0074] The inline feeder apparatus shown generally as 30 operates as follows:
[0075] (a) storing parts in hopper 32 ; delivering said parts to an elevator 52 ;
[0076] elevating and delivering said parts to a linear feeder 70 ;
[0077] sensing excessive part load on linear feeder;
[0078] reducing part loading by reducing elevator 52 stroke or frequency;
[0079] feeding parts through an intelligent tooling plate having second part sensor 84 and third part sensor 90 .
[0080] Alternate Method of Operation
[0081] (b) storing parts in a hopper;
[0082] delivering said parts to an elevator;
[0083] elevating and delivering said parts to a linear feeder;
[0084] sensing and clearing misoriented or jammed parts from a linear feeder prior to entering tooling plate;
[0085] feeding said parts through an intelligent tooling plate.
[0086] An Alternate Method of Operating Inline Feeder
[0087] (c) storing parts in a hopper;
[0088] delivering said parts to an elevator;
[0089] elevating and delivering said parts to a linear feeder;
[0090] sensing excessive part load on linear feeder;
[0091] reducing part load by reducing elevator stroke or frequency;
[0092] sensing misoriented parts at clearing station;
[0093] clearing misoriented or jammed parts using compressed air from linear feeder at clearing station;
[0094] feeding correctly oriented parts through an intelligent tooling plate.
[0095] An Alternate Method of Operating Inline Feeder
[0096] (d) storing parts in the hopper;
[0097] delivering said parts to an elevator;
[0098] elevating and delivering said parts to a linear feeder;
[0099] clearing misoriented or jammed parts from linear feeder;
[0100] feeding said parts to intelligent tooling plate;
[0101] sensing through put and jams through said tooling plate;
[0102] clearing tooling plate of jams.
[0103] Additionally the above described inline feeder provides a counter flow or opposing flow of parts namely parts flow in direction 36 along vibratory hopper 32 and flow in the opposite direction along linear feeder 70 .
[0104] It should be apparent to persons skilled in the arts that various modifications and adaptation of this structure described above are possible without departure from the spirit of the invention the scope of which defined in the appended claim. | An inline feeder for delivering oriented parts, said inline feeder including a hopper section including a vibratory hopper for storing parts and transporting parts to an elevator section including an inclined elevator for receiving parts from said vibratory hopper and depositing said parts onto a linear feeder. Said inline feeder further including a part sensor for sensing flow of parts along said linear feeder, said sensor sensing flow and orientation of said parts on said linear feeder; and a an air fitting/valve for applying a burst of compressed gas against a part for rejecting and removing said part from said linear feeder, wherein said air valve operably in communication with said part sensor means for triggering a part rejection due to misorientation or jammed parts from said linear feeder and allowing properly oriented parts to be delivered. | 1 |
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation-in-part of U.S. patent application, Ser. No. 06/367,262, filed Apr. 12, 1982.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to the refining of metals containing residual metals as impurities.
2. Description of the Prior Art
Many metals include small amounts of other metals, as residual metals, following smelting and preliminary refining operations. Scrap metals from various sources may also comprise residual metals.
The presence of residual metals often deleteriously affects the properties or workability of the contaminated metal, and removal of such residual metals is desirable.
It has previously been proposed to remove residual metals from molten steel by vacuum treatment. See, for example, Salomon-de Frieberg and Davenport, `Vacuum Removal of Copper from Melted Steel Scrap`, The Metallurgical Society of CIM, Annual Volume, 1977; Harris and Davenport, `Pilot Plant Scale Vacuum Distillation of Liquid Steel to Remove Copper`, Canadian Metallurgical Quarterly, Volume 18, 1979; Harris and Davenport, `Vacuum Distillation of Liquid Metals: Part 1, Theory and Experimental Study`, Metallurgical Transactions B, Volume 13B, December 1982, pages 581-591; and U.S. Pat. No. 4,227,922.
The work outlined in these prior references was particularly concerned with removal of residual metals from molten steel as distinct from other metals.
In U.S. patent application Ser. No. 367,262, the applicants disclosed the refining of steel containing residual metals and impurities and apparatus for this purpose. An essential feature of the described refining process is the subjection of the liquid steel containing metallic impurities in a bath, to a vacuum effective to cause emission from the liquid steel surface of the metallic impurities as a flow of rising gases. According to the invention, the surface of the molten steel is maintained substantially free of surface contamination and return of the residual metals into the molten steel is continuously prevented. Vacuum is maintained, throughout the treatment, at a level at which the emission is in the form of a bulk flow of rising gases which, in combination with the continual freeing of the surface of contamination and the continual prevention of the return of the impurities, reduces the time of the removal of impurities substantially to a minimum.
The applicants have also disclosed the use of a lifting gas, to lift liquid steel from a lower level in the bath to above the surface of the bath, and discharging the lifted steel to the surface of the bath to maintain it free of contamination. This latter expedient also has the advantage of exposing a large surface area of the lifted steel to the vacuum.
SUMMARY OF THE INVENTION
The applicants have now found that vacuum techniques are also applicable to the removal of metallic impurities from other molten metals, for example, aluminum, nickel, cobalt, titanium, and copper.
However, these metals all have their own special characteristics which must be taken into consideration when applying vacuum treatment. In operation a vacuum is maintained at a pressure lower than the vapor pressure of the molten metal. This may be practical in the case of molten steel, however, the group of metals comprising aluminum, nickel, copper, cobalt and titanium has such a low vapor pressure that it is difficult, if not impossible, to provide a lower vacuum pressure and this has discouraged researchers from attempting to remove metallic impurities from such metals by vacuum treatment.
In particular, liquid aluminum, copper, cobalt, nickel and titanium all have vapor pressures of less than about 1 pascal, whereas liquid steel has a vapor pressure of about 10 pascals.
The applicants have now found, however, that this problem can be overcome by combining the vacuum treatment with the injection of a lifting gas to supplement the emission of gas from the molten metal surface, and thus build up the bulk flow of rising gases to the point where effective removal of the metallic impurities or residual metals can be obtained at a rate sufficiently high as to make the process practical commercially.
The rate of emission of the impurity metals from the molten metal surface is controlled by three factors:
(a) transport of the metal to the molten metal surface from within the body of molten metal,
(b) evaporation of the metal at the molten metal surface, and
(c) transport of the evaporated metal away from the metal surface.
The factors which determine the rate of impurity removal when vacuum refining metals having low vapor pressure depends on the impurity being removed. Specifically, removal of impurities with high vapor pressure over the melt is controlled by factor (c), whereas removal of impurities with low vapor pressure will be controlled by factor (b). Removal of impurities with intermediate vapor pressure is controlled by both factors (b) and (c). The following Table lists for the low vapor pressure metals, the factor or factors which determine the rate of the particular impurity removal.
______________________________________ Low Pressure MetalImpurity Copper Aluminum Cobalt Nickel Titanium______________________________________Silver b -- b/c b/c --Arsenic b -- -- b/c --Bismuth c -- c c --Copper -- -- c b bIron -- b b -- bLithium -- c -- -- --Lead c c c c cMagnesium -- c -- -- --Sodium -- c -- -- --Tin -- b b b bZinc c -- c c --______________________________________
In accordance with the present invention, a lifting gas is continuously injected into the molten metal to provide a lifting gas which enhances the bulk flow, i.e. factor (c) and forms a metal fall, thereby increasing the surface area of molten metal and thus enhancing the evaporation, i.e. factor (b).
However, the present invention also comprises the additional feature of creating a high level of melt mixing. This aspect of the invention also minimizes the effect of factor (a) and results in rates of refining which are impossible to attain in existing vacuum refining apparatus, for example, electron beam type vacuum refining apparatus in which a calm shallow bath is exposed to very high vacuum.
In accordance with the invention, there is provided a method of vacuum refining a molten metal having a low vapor pressure comprising forming a mixture of rising lifting gas and metallic gases evaporating from the surface of the molten metal, and subjecting the surface of the molten metal to a vacuum effective, in the presence of the lifting gas, to cause a bulk flow of rising gases from the molten metal surface, said vacuum having a pressure higher than the pressure required to cause a bulk flow of rising gases in the absence of lifting gas.
In particular the mixture may be formed by injecting the lifting gas through the molten metal and discharging liquid metal entrained in the lifting gas above the molten metal surface to drop in a metal fall onto the molten metal surface.
In a particular embodiment of the invention, there is provided a process for removing metallic impurities from a metal having a low vapor pressure, for example, aluminum, copper, cobalt, nickel and titanium, particularly metals having vapor pressure of less than 5 pascals at 100 ° K above their melting point, comprising, selecting an apparatus with a receptacle containing a bath of a molten metal having a low vapor pressure in a vacuum chamber and at least one conduit extending from below the surface of the molten metal to a point above the molten metal to provide for a metal fall, condensing means in the upper reaches of the vacuum chamber for condensing rising metallic gases, continuously injecting a lifting gas into a lower part of said conduit whereby liquid metal is lifted therethrough and discharged in finely divided form to drop in a metal fall onto the surface of the molten metal in the receptacle and a mixture is formed of said lifting gas and gases evaporating from said molten metal, subjecting the vacuum chamber to a vacuum effective, in the presence of the lifting gas, to cause a bulk flow of rising gases between the molten metal surface and the condensing means, said vacuum being lower than that which would cause a bulk flow of rising gases in the absence of lifting gas, continuously condensing the metallic rising gases on the condensing means to prevent reflux of impurities into the molten metal, thereby to increase the speed of removal of metallic impurities, restoring the pressure to normal, and recovering the treated metal.
Bulk flow of evaporated vapor, from the liquid metal surface to the condensing surfaces, differs in kind from diffusion of the evaporated vapor through the gas phase between the metal surface and the condensing surfaces. With bulk flow, there is a high mean velocity (up to several hundreds of meters a second) of evaporated vapor from the molten metal surface towards the condenser surfaces, which the applicants have observed, optically, as a directional stream leading towards the condenser surfaces. This contrasts with diffusion which takes place when the chamber pressure is greater than the melt vapor pressure, no directional (negligible net velocity) stream was observed, only a relatively stationary cloud of metal vapor.
In the case of molten copper the applicants also observed, not only that bulk flow of vapor away from the liquid metal can be achieved by decreasing the pressure within the vacuum chamber, but that the onset of bulk flow corresponds to a chamber pressure equal to the melt surface vapor pressure, and decreasing chamber pressure further increases the velocity of this bulk flow and evaporation rate. The applicants have also observed, in the case of molten copper that the evaporation rate reaches a maximum when chamber pressure is at a level of 10% to 30% of the total vapor pressure of the molten copper, and that operating within this range maximizes evaporation rate, while, at the same time, minimizes the expense of producing higher vacuum with the resultant wear and tear on the system.
Surprisingly, therefore, in face of prior art findings that vacuum treatment is too slow to be practical, through the use of the invention, a user is now able to obtain a substantially maximum refining rate for any given heat of copper and other metals having a low vapor pressure, and a practical treatment time of not more than about one hour, or even less, where the required tolerance of impurities is higher.
In the embodiments in which a lifting gas is employed, particularly for the case in which the molten metal has a low vapor pressure, for example, aluminum, it is found to be appropriate to inject the lifting gas so as to establish a bulk gas velocity in the bulk flow of rising gases of about 1 to about 100, preferably about 5 to about 20, meters per second; the bulk gas velocity being calculated across a horizontal cross-section taken through the body of the rising gases between the surface of the molten metal and the condensing surfaces.
An important criterion in successful operation is the lift factor or the overflow to submergence ratio, which is suitably 0.01 to 3 and preferably 0.5 to 1.5.
The lift factor is defined as the ratio of the lift height, i.e. the vertical distance from the surface of the molten metal in the vacuum chamber to the upper end of the lift conduit, to the gas injection nozzle submergence, i.e. the vertical distance from the surface of the molten metal in the vacuum chamber to the outlet of the injection nozzle.
The lifting gas is injected into the molten metal by means of an injection nozzle having its outlet adjacent the lower end of a vertical lift conduit through which the lifting gas rises, the conduit terminating at its upper end above the surface of molten metal in the vacuum chamber.
The lifting gas is suitably injected through the nozzle at a rate of 1 to 500 kg per hour for a bath of molten metal mass commensurate with associate processing facilities. A surface area exposed to vacuum of about 5 to about 500, preferably 70 to 110 m 2 is created by the metal spray during the metal fall.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention is illustrated by reference to the drawings, in which:
FIG. 1 is a vertical cross-section through a vacuum treatment apparatus in which molten metal is lifted from the level of the bath, and the residual metals are collected in liquid form;
FIG. 2 is a horizontal cross-section along the line 2--2 of FIG. 1; and
FIGS. 3 and 4 show alternative embodiments of the apparatus in which residual metals are collected in solid form.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
With further reference to FIGS. 1 and 2, A designates a refractory lined ladle. B identifies a vacuum chamber as a whole. The unit B includes a conduit 17 leading to a vacuum pump (not shown). The vacuum chamber B has a refractory lined steel shell 14. The unit B includes a removably connected hood 16.
A vapor condensing arrangement C, made up of a number of plates 33 having extensive surfaces, is located in the chamber 15. The plates 33 have feet 34 resting in a condensate collection trough 35. At their upper ends, the plates abut to form a central joint 37. The condensate trough 35 extends right around the chamber B and leads to a barometric leg 36 at one side of chamber B. The leg 36 leads to a collection vessel 38.
In the hood 16 is mounted heat transfer element 26. The element 26 may serve either to supply heat to or remove heat from the plates 33, as required.
Hollow leg or conduit 21 leads from below the surface of the metal in the ladle A, to the bottom of the receptacle 19.
A second hollow leg 23 leads from the level of the liquid metal in ladle A to well above the level of the metal in the receptacle 19 and terminates in a gooseneck part or hood 25 having an outlet 27 above the surface of the molten metal.
The legs 21 and 23 are of refractory material, for example, alumina, silicon nitride or stabilized zirconia. A lance 29 leads from a source (not shown) of lifting gas to a bottom part of the leg 23 where it terminates in an inlet or nozzle 31.
The nozzle 31 is preferably designed to produce large bubbles to create plug flow within the conduit 23. Plug flow is the condition created by a series of spaced-apart bubbles, which each occupy the entire cross-section of the up-leg 23. To this end, the nozzle should have an orifice Reynolds number less than 500. In the event of injecting a reactive gas, the nozzle 31 may be provided with protective means against thermal and chemical degradation. For example, it may have means for simultaneously injecting cooling or endothermic shrouding gas annularly about a main nozzle.
In operation, the molten metal is lifted by the lifting gas to well above the level of the molten metal in the receptacle 19. As the molten metal passes through the gooseneck part 25, its path is inverted, and it is released in finely divided form through the outlet 27. The lifting gas and the gas from the distillation of metallic impurities expands violently, dispersing the liquid metal within the gooseneck 25. The resulting explosive mixture of molten metal, inert gas and gasified volatile metals is expelled downwards, so that the metal is sprayed from the outlet 27 in finely dispersed form of streams and drops and bombards the surface of the molten metal bath 41 in the receptacle 19, keeping it free of surface film. At the same time, the gaseous content of flow in leg 23 separates from the metal and leaves the outlet 27 whence it rises upward. The condensable gases (metallic impurities) are intercepted by the condensing surfaces 33 on which they condense as liquid. The non-condensable lifting gas flows out through the exhaust passage 17.
The liquid from the surfaces 33 runs to the receiving trough 35 and is led therefrom through the barometric leg 36 to the collecting vessel 38.
Placing the outlet 27 sufficiently far above the level of the surface of the molten metal in the receptacle 19 provides a fall to the molten metal surface effective to furnish good evaporation from the falling metal droplets and leave should be taken to place the condensing surfaces 33 as close as possible to the molten metal surface without being close enough to be splashed.
FIGS. 3 and 4 illustrate in vertical cross-section further forms of units which may be employed in the processes of the invention. Similar reference letters and numerals have been applied to the various parts except that the letters have been given a respective subscript 4 and 5 and the reference numerals are in the 400's and 500's. The arrangements of FIGS. 3 and 4 place the respective up-leg 423 and 523, respectively, in position where the sidewall of the vessel is employed as part of it and the leg is less exposed to temperature and other effects within the vacuum chamber.
In FIGS. 3 and 4, the metallic vapors are condensed to a solid and, therefore, the barometric leg and the collecting vessel are omitted. The operation is similar to that of the unit of FIG. 1, with the exception that the condensate is collected and disposed of as a solid, rather than a liquid.
The condensable gases (gasified metals) strike the surfaces of the plates 433 (533) and are condensed to a solid while the non-condensable gases are separated therefrom and withdrawn through the conduit 417 (517) by the vacuum pump. The temperature of the plates 433 (533) must be maintained within a range low enough to condense the metallic gases as a solid and yet high enough to prevent too great a heat loss from the chamber. The solid condensate is recovered by removing the condenser plates 433 (533) from the chamber and heating them to the condensate melting temperature in a furnace having a reducing atmosphere.
VARIABLE FACTORS
The process of the invention is subject to variable factors which will be discussed as follows:
Starting Materials
The nature of the starting material, which may be determined by analysis, will determine, to some extent, the optimum conditions employed, and these may be arrived at by experiment.
Condenser Temperature
There are two possible modes of condenser operation; one in which the gasified metallic vapors are condensed as liquid and the other in which it is condensed as solid. To this end, the temperature of the condenser controls in which mode the unit operates.
In the liquid condensing mode, the condenser temperature depends on the composition of the condensing vapors. At the commencement of refining the condensate has a lower melting point because there is a higher proportion of impurities in the vapor condensing compared to the latter stages when the proportion of the metal undergoing refining is greater.
In the solid condensing mode, the condenser temperature is adjusted so that at no time does the condensate liquify. As in the liquid condensing case, condenser temperature can increase throughout a treatment because the melting point of the condensate increases as the quantity of impurity decreases with respect to the amount of iron evaporating.
Liquid Metal Temperature
The temperature of the liquid metal is primarily determined by the tapping temperature of the prior operation less any temperature loss associated with the transfer of the ladle of liquid metal to beneath the distillation unit. Liquid metal temperature then continues to decrease (unless some corrective action is taken) due to further heat losses from both the ladle and distillation unit.
In starting up, the entire unit should be preheated to operating temperature and the proper differential between the temperature of the gas coming off and the temperature of the condenser.
Time
The processing time may range up to one hour. Processing time is affected by
(i) amount of refining desired: 0 to substantially 100% elimination of initial impurities (preferred, 75-90% elimination);
(ii) liquid metal temperature;
(iii) agitation: quiescent to violent turbulence (preferred, violent turbulence);
(iv) distillation unit interior pressure;
(v) injected gas flow rate.
Pressure
Distillation unit interior pressure varies from atmospheric, between cycles and when the unit is not in operation, to pressures which will normally be in the range from 100 to 500 pascals during treatment.
The chamber pressure should be reduced to the operating level as fast as possible. This increases the productivity of the process.
Mixing or Lifting Gas
The mixing or lifting gas may be any non-condensable gas comprising either pure gas or a mixture of gases where the gases may be either reactive or inert. Preferably, it is argon gas mixed with quantities of either oxidizing gases such as oxygen or carbon dioxide or reducing gases such as carbon monoxide or hydrocarbon gas. (Nitrogen could be used in the process to reduce cost in cases where it is non-reactive. Freon (trade mark of E.I. Du Pont de Nemours & Co. for a series of fluorocarbon products) could be used in conjunction with an inert gas when chlorination and/or fluorination is desired).
Characteristics of the Bath of Molten Metal
A bath of molten metal within the distillation unit (i.e. above the legs) acts as a collector for the liquid metal which has been lifted via the up-leg and as a site for elimination of impurities leaving the surface directly.
The bath depth may be in the range 0.01 to 1.0 m (preferred 0.2 to 0.5 m). Bath surface area may range from 0.06 m 2 to 0.033 m 2 per tonne of metal treated. Bath volume in the range 0.006 m 3 to 0.033 m 3 per tonne of metal treated.
Condenser
The condenser leads evaporated volatile metal vapor away from the liquid metal surface by virtue of placing a sink for the metal vapor at a location remote from the liquid metal surface. The area of the condensing surface is large enough so that the liquid condensate forms either a liquid film which will adhere to and flow down the surface and into the condensate trough without dripping off the surface back into the molten metal or a solid mass which will not interfere with the flow of non-condensable gas to the outlet.
The condenser has sufficient surface area to capture 100% of the condensable gases evolving in the distillation unit. Its surface area is in the range 3 m 2 to 0.3 m 2 per tonne of metal treated (preferred 0.60 m 2 to 0.35 m 2 per tonne of metal treated.
Process Reactions
The reactions occurring during treatment are as follows:
______________________________________(i) In the case of an inert lifting gas: ##STR1##condensed impurities(ii) In the case of an oxidizing lifting gas: ##STR2##condensed impurities(iii) In the case of a reducing lifting gas: ##STR3##condensed impurities______________________________________
Agitation
Agitation contributes to creating a clean surface area on the metal in the receptacle for exposure to the action of the vacuum, increases the surface area exposed to vacuum, and increases the liquid phase mass transfer. All these factors increase the refining rate.
In the distillation unit, agitation is caused by the rise of the gas bubbles through the liquid metal and their breaking through the liquid metal/vacuum interface.
Materials of Construction
The distillation unit has a demountable vacuum-tight steel casing which supports the inner refractory lining. The unit is designed to treat all grades of steel and iron alloys and therefore the lining material is resistant to both chemical and thermal degradation. The most common and readily available grades suitable for application in each area of the unit should be used having regard for the new more expensive, but more robust grades of refractories such as those manufactured from silicon nitride, zirconia or alumina based refractory ceramics.
EXAMPLE 1
The following is an example of treating copper. The copper treated was impure copper containing:
______________________________________ 0.0001-0.05-0.5-1.0% Bi 0.0001-0.05-3.0-5.0% As 0.0001-0.05-0.5-1.0% Sb 0.0001-0.05-3.0-5.0% Pb 0.0001-0.05-3.0-5.0% Sn 0.0001-0.002-0.08-0.2% Ag 0.0001-0.05-0.5-1.0% Cd 0.0001-0.05-0.5-1.0% Mg 0.0001-0.05-0.5-1.0% Mn______________________________________
The operating temperature was within the range from 1350° K to 1800° K (preferred range 1525° to 1600° K). The chamber pressure was from 1 to 1000 pascals (preferably 100 to 500 pascals and in particular 133 pascals).
In order to achieve 80% removal of bismuth within one hour from a 35 kg bath of copper, a surface area of about 0.3 square meters, was exposed to vacuum via the action of the lift-spray apparatus. This represents about a ten-fold increase in bath surface area compared to quiescent conditions. The bulk gas velocity was from 1 to 100 meters per second, 5 to 20 meters per second being preferred.
Lifting gas was injected at a flow rate of about 90 grams per hour. The lift height was about 0.1 to 0.3 meters.
EXAMPLE 2
The following is an example of treating 35 tons of molten aluminum. The operating temperature is within the range from 900° to 1300° Kelvin (1050° to 1150° Kelvin preferred). The chamber pressure is from 1 to 1000 pascals, 100 to 500 pascals being preferred. The starting aluminum has a composition containing 0.01 to 5.0% magnesium.
In order to obtain 80% removal of the magnesium, within 30 minutes, a surface area of molten metal, preferably 80 to 110 m 2 is exposed to vacuum, and bulk gas velocity of 5 to 20 meters per second of lifting gas.
The flow rate of the injected lifting gas was about 70 kilograms per hour.
The lift height was about 0.5 to 1.5 meters. | Molten metals having a low vapor pressure, such as aluminum, are vacuum refined to remove metallic impurities employing a lifting gas to form a metal fall above a liquid metal surface; a vacuum above the metal surface is effective in conjunction with the lifting gas, to develop a bulk flow of rising gases between the liquid metal surface and a condenser; the pressure is higher, i.e. lower effective vacuum, than that which would cause such bulk flow in the absence of the lifting gas; a molten metal such as copper may be vacuum refined by creating a vacuum effective to cause emission from the liquid copper surface of the metallic impurities as a bulk flow of rising gases, in particular lifting the liquid copper from a lower level to at least the metal surface creates a circulation within the mass of copper effective to promote transfer of metallic impurities to the metal surface. | 2 |
BACKGROUND
1. Field of the Invention
The present invention relates to a composition that helps reduce hooks or slices in golf shots, and more particularly a composition that is applied to the hitting face of a golf club.
2. Background of the Invention
One of the most frustrating aspects of golf is a tee shot that goes awry. Putting and short range chipping can also be problems for golfers, but if the first shot is not reasonable, the next several strokes may be recovery shots or shots from bad angles or lies, that is, if the golfer can even find the ball.
Typically, the hook or slice is caused by a poor grip. Sometimes, the swing is at fault. Regardless, unless the golfer has practiced and practiced, it is likely that many of the tee shots will either hook or slice. For the casual player or "hacker," driving the first shot into the woods or out of bounds limits the enjoyment of the game. Many people simply do not have the time or patience to practice grips or swings, and when given the opportunity to play, the occasional golfer may choose not to play to avoid either embarrassment or spending several hours "in the woods."
Even more seasoned players who only occasionally hook or slice sometimes need to consistently hit straight balls for practice. For example, when trying to judge distances that the golfer hits the ball with a particular club, slices and hooks only waste time or causes inaccurate measurements.
DETAILED DESCRIPTION
The present invention provides a composition for application to devices typically used to strike a moving or stationary object and project it at a distance. Most typically, the composition is applied to a golf club head/face, although other applications are within the scope of the invention. The composition substantially reduces spin on an impacted golf ball, resulting in a substantially straight-line pathway of the ball. The substantially straight-line pathway results regardless of the style or form of a golf swing. The composition is applied to, and adheres to the golf club face for the duration of the golf swing. After impact, the golf club face and the golf ball are substantially free of the composition.
Typically, sufficient impact between a golf club face and a golf ball will project the golf ball through the air in a forward direction. Due to friction between a golf club face and the golf ball during impact, a spin component may be imparted to the golf ball. Therefore, the golf ball may significantly diverge from a substantially straight-line pathway depending on the direction of the spin component. Removing the spin component from the golf ball would allow the impacted golf ball to follow a more substantially straight-line pathway.
In one aspect of the present invention, a composition includes a saturated oil, a water-soluble lubricant and an aqueous carbon dioxide solution. The present composition including the unsaturated oil reduces the friction between the golf club face and the golf ball, and substantially reduces the spin component on the golf ball after impact. "Saturated oil" as used herein refers to an oil in which a primary component molecule is free of double bonds. In one embodiment of this aspect of the invention, the saturated oil is a hydrocarbon having a formula C n H 2n +2. In another embodiment of the composition, the saturated oil is a "petrolatum," which as used herein, is defined as a purified colloidal mixture of non-straight-chain solid hydrocarbons and high-boiling liquid hydrocarbons. The petrolatum can be selected from the group consisting of petroleum jelly, paraffin jelly, vasoliment, and mixtures thereof. A commercially available petrolatum is White Protopet 1S.sup.®, available from Witco Corp., Greenwich, Conn. In another embodiment, the saturated oil is a silicone having a repeat unit of --[R 2 Si --O] n -- wherein the value "n" is an integer.
The composition has a viscosity sufficient to adhere to the golf club face for the duration of a golf swing. The adherence of the composition and the sufficiency of the viscosity of the composition, can be measured by a viscosity screening test. The test includes measuring and applying an amount of the composition to a golf club face, swinging the golf club with a standard golf swing, and measuring the amount of the composition remaining on the golf club face. The step of swinging the golf club does not involve actually impacting a golf ball, but does include the substeps of a standard golf swing having a rotation of at least 180°, with a back swing and a forward swing having sufficient force to project a golf ball. If the viscosity of the composition is too low, it will run down the golf club face immediately after application. A highly viscous composition will adhere to the golf ball after impact. Accordingly, another viscosity screening test involves applying the composition to the golf club face, impacting a golf ball to project the ball, allowing the ball to come to rest, and assessing whether the golf ball is substantially free of the composition.
The composition also has a volumetric shape upon applying the composition to the golf club face. The volumetric shape is typically spherical with a diameter of at least about 5 mm and is an important parameter in determining whether a sufficient amount of the composition is applied to the golf club face to contact the ball. The volumetric shape allows the composition to be used economically in that a large percentage is not wasted by spreading it over the entire golf club face, as would be necessary with a low viscosity compound that does not have a volumetric shape. The present composition has sufficient viscosity to maintain the volumetric shape for the duration of the golf club swing. The composition's volumetric shape can be evaluated by applying the composition of a particular volumetric shape to the golf club face, swinging the golf club with a standard golf swing, and assessing whether the volumetric shape after swinging resembles the volumetric shape before swinging. As with the viscosity screening test, the step of swinging the golf club does not involve actually impacting a golf ball.
To achieve the desired viscosity levels for the composition, the saturated oil has a desired viscosity range. The National Lubricating Grease Institute (NLGI) provides a standard to assess viscosity levels. For example, a lubricant having an NLGI grade of 1 has the viscosity of a semisolid liquid, whereas a lubricant having an NLGI grade of 3 has the viscosity of a thick paste. Preferably, the saturated oil has an NLGI grade of between about 1 and about 3; more preferably, the saturated oil has an NLGI grade of between about 1.5 and about 2.5, and more preferably still, the saturated oil has an NLGI grade of between about 1.75 and about 2.25.
In another embodiment, the saturated oil is a "liquid petrolatum," which as defined herein, is a mixture of liquid hydrocarbons derived from petroleum. Petroleum comprises a mixture of hydrocarbons obtained from crude oil, mineral oil, rock oil, coal oil or seneca oil. Petroleum may also contain small amounts of benzene hydrocarbons, sulfur and oxygenated compounds. The liquid petrolatum can be selected from the group consisting of liquid paraffin, mineral oil, white mineral oil, paraffin oil and mixtures thereof. In another embodiment, the saturated oil is a mixture of petrolatum and liquid petrolatum in a ratio of between about 1:1 to about 10:1. A preferred ratio of petrolatum and liquid petrolatum is 8:1. In a preferred embodiment, the saturated oil is a mixture of petroleum jelly and mineral oil. In this embodiment, the liquid petrolatum functions to improve the miscibility of the composition and fine tune the viscosity of the composition to a desired level.
The composition has a compressibility sufficient to allow a substantial amount of the composition to remain between the golf club face and the golf ball during impact. Unlike gases, liquids are generally noncompressible. Thus, applying a liquid to a golf club face and impacting a golf ball forces the liquid out from under the ball. The present composition includes a substance that allows the composition to become compressible. Moreover, the golf ball and golf club face is preferably substantially free of the substance after impact. In a preferred embodiment, the substance is an aqueous carbon dioxide solution. Because of carbon dioxide gas bubbles in the aqueous solution, the resulting composition is physically compressed during impact between the golf club face and the golf ball. The aqueous carbon dioxide solution can be prepared by methods known to those of ordinary skill in the art. For example, subjecting water to carbon dioxide under a pressure of 70 psi or even lower, will readily produce a saturated aqueous carbon dioxide solution.
Aqueous solutions, including aqueous carbon dioxide solutions, are immiscible with the saturated oil in the present composition. Thus, the present composition also includes a water-soluble lubricant. Preferably, the water-soluble lubricant is a cellulose gel, which is typically provided as a powder and commonly sold as a food additive and fluid thickener. In the present composition, the aqueous carbon dioxide solution is initially mixed with the water-soluble lubricant prior to the addition to the saturated oil. To keep the solution saturated with carbon dioxide, the initial mixing is performed in a carbon dioxide-rich environment. The mixing step is typically performed at room temperature and atmospheric pressure and is complete when the composition has a homogeneous texture and color.
Other desirable attributes of the present composition relate to product safety and stability issues. Each substance in the composition has low toxicity levels and is used in a number of cosmetic and health care products. Consequently, contacting the composition with the skin provides relatively low health risks. The composition does not degrade under ordinary conditions of use, and moreover, the composition does not degrade other substances. Golf clubs, notably the woods, are typically covered with a finish coating that will not be compromised by use of the present composition.
Having thus described various embodiments of the invention, numerous modifications within the scope of the invention will occur to those skilled in the art. Thus, this description is provided by way of example only and is not intended to be limiting. The function and advantage of these and other embodiments of the present invention will be more fully understood from the example below. The following example is intended to illustrate the benefits of the present invention, but does not exemplify the full scope of the invention.
EXAMPLE 1 PREPARATION OF THE COMPOSITION
The example provides one quart of the composition. Four units of a water soluble lubricant such as KY Jelly® lubricant, available from Johnson & Johnson, New Brunswick, N.J., were combined with 1 unit of cold soda water. One drop of vegetable dye was added. The mixture was whipped to an even consistency with a mixer under a carbon dioxide-rich environment until the mixture had a homogeneous consistency and color. Eight units of the protopet 1S®, available from, Witco Corp., Greenwich, Conn., and one unit of mineral oil were combined and mixed to an even consistency. The water soluble lubricant mixture and Proto pet mixture were then combined in a mixer supplied with a gas inlet. The atmosphere in the blender was replaced with carbon dioxide and the mixture was whipped for approximately five minutes or until the mixture achieved a homogeneous consistency and color.
Those skilled in the art would readily appreciate that all parameters listed herein are meant to be exemplary and that actual parameters will depend upon the specific application for which the methods and apparatus of the present invention are used. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, the invention may be practiced otherwise than as specifically described. | The present invention relates to a method for hitting an object in a substantially straight-line pathway. The method comprises the steps of applying a composition to a hitting surface and impacting the object. In particular, the composition can be applied to a golf club face to reduce hooks or slices. The composition is a product of a mixture comprising a saturated oil, a water soluble lubricant and an aqueous carbon dioxide solution. | 2 |
PRIORITY
[0001] The present patent application claims priority from U.S. Ser. No. 61/219,909 filed on Jun. 24, 2009, the entire contents of which are incorporated herein by reference.
FIELD
[0002] The present patent application relates to compositions that include copper and carbon and, more particularly, to copper-carbon compositions that do not phase separate when melted or re-melted.
BACKGROUND
[0003] Copper metal is commonly used in various electrical and mechanical applications due to its relatively high electrical and thermal conductivity. However, copper metal is very ductile, which limits its use in mechanical and structural applications. Furthermore, copper metal tends to corrode and oxidize over time, thereby limiting its application in various reactive environments.
[0004] Copper-carbon composites have been developed in an effort to improve upon the thermal, mechanical and chemical properties of copper metal. Copper-carbon composites are formed by mechanically introducing carbon to copper metal, thereby imparting the resulting copper-carbon composite material with certain advantages (e.g., improved thermal conductivity) over pure copper metal. For example, copper-carbon composites have been prepared using copper and carbon powder metallurgy techniques, as well as by heating and kneading copper and carbon together.
[0005] However, like copper metal, copper-carbon composites have physical properties that limit their usefulness in certain applications. For example, the carbon in copper-carbon composites phase separates from the copper metal when the composite is melted, thereby limiting the usefulness of copper-carbon composites in high temperature applications.
[0006] Accordingly, those skilled in the art continue to seek improvements in the properties of copper metal.
SUMMARY
[0007] In one aspect, the disclosed copper-carbon composition may include copper and carbon, wherein the copper and the carbon form a single phase material, and wherein the carbon does not phase separate from the copper when the material is heated to a melting temperature.
[0008] In another aspect, the disclosed copper-carbon composition may consist essentially of copper and carbon, wherein the copper and the carbon form a single phase material, and wherein the carbon does not phase separate from the copper when the material is heated to a melting temperature.
[0009] In yet another aspect, the disclosed copper-carbon composition may consist essentially of copper and carbon, wherein the copper and the carbon form a single phase material, the carbon comprising at least about 0.01 percent by weight of the material, and wherein the carbon does not phase separate from the copper when the material is heated to a melting temperature.
[0010] Other aspects of the disclosed copper-carbon composition will become apparent from the following description, the accompanying drawings and the appended claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIG. 1 is a scanning electron microscope image of the disclosed copper-carbon composition, the image showing a 30 μm wide portion of the composition;
[0012] FIG. 2 is a scanning electron microscope image of the disclosed copper-carbon composition, the image showing a 3 μm wide portion of the composition;
DETAILED DESCRIPTION
[0013] It has now been discovered that carbon can be incorporated into copper metal in substantial quantities to form a single phase material, and in such a way that the carbon does not phase separate from the copper when the material is melted.
[0014] Specifically, it has now been discovered that carbon can be incorporated into copper metal by melting the copper metal, mixing the carbon into the molten copper metal and, while mixing, applying a current of sufficient amperage to the molten mixture such that the carbon becomes incorporated into the copper metal, thereby forming a single phase copper-carbon material. The resulting single phase copper-carbon material does not phase separate when subsequently re-melted (i.e., raised to a temperature at or above the materials melting temperature).
[0015] The carbon in the disclosed copper-carbon composition may be obtained from any carbonaceous material capable of producing the disclosed copper-carbon composition. For example, high surface area carbons, such as activated carbons, and certain functionalized carbons have yielded desirable results. Another example of a useful carbonaceous material is an allotrope of carbon, such as diamond, graphite and Buckminster fullerenes. While those skilled in the art can appreciate that many different forms of carbon exist, without being limited to any particular theory, it is believed that certain forms of carbon yield the disclosed copper-carbon composition, while others do not.
[0016] The copper in the disclosed copper-carbon composition may be any copper or copper alloy capable of producing the disclosed copper-carbon composition. Those skilled in the art will appreciate that the selection of copper may be dictated by the intended application of the resulting copper-carbon composition. For example, when high electrical conductivity is desired, oxygen free, high purity copper metal may be used and the disclosed copper-carbon composition may be formed in a vacuum or under a blanket of oxygen-free and electrically non-conductive gas.
[0017] In one aspect, the disclosed copper-carbon composition may comprise at least about 0.01 percent by weight carbon. In another aspect, the disclosed copper-carbon composition may comprise at least about 0.1 percent by weight carbon. In another aspect, the disclosed copper-carbon composition may comprise at least about 1 percent by weight carbon. In another aspect, the disclosed copper-carbon composition may comprise at least about 5 percent by weight carbon. In another aspect, the disclosed copper-carbon composition may comprise at least about 10 percent by weight carbon. In another aspect, the disclosed copper-carbon composition may comprise at least about 20 percent by weight carbon. In yet another aspect, the disclosed copper-carbon composition may comprise at least about 53 percent by weight carbon.
[0018] As used herein, the terms “single phase” and “phase separate” refer to phases discernable by the naked eye or using only slight magnification (e.g., at most about 100 times magnification). Therefore, a material appearing as a single phase to the naked eye, but showing two distinct phases when viewed on the nano-scale should not be construed as having two phases.
[0019] While the exact chemical structure of the disclosed copper-carbon material is currently not known, without being limited to any particular theory, it is currently believed that the steps of mixing and applying electrical energy result in the formation of chemical bonds between the copper and carbon atoms, thereby rendering the disclosed copper-carbon compositions unique vis-à-vis known copper-carbon composites and solutions of copper and carbon. Furthermore, without being limited to any particular theory, it is believed that the disclosed copper-carbon material may be a nano-composite material. Still furthermore, without being limited to any particular theory, it is believed that the amount of electrical energy (e.g., the current) applied to form the disclosed copper-carbon composition should be sufficient to initiate an endothermic chemical reaction between the copper and the carbon.
[0020] The disclosed copper-carbon compositions will be better understood with reference to the following examples:
EXAMPLES
Example 1
[0021] A graphite crucible (electrically coupled to ground) was positioned in a gas heated furnace. The crucible was charged with 100.795 ounces of 99.999 percent pure oxygen free, high purity (“OFHP”) copper. The OFHP copper was cut from a rod obtained from ThyssenKrupp Materials NA of Southfield, Mich.
[0022] Once the copper in the crucible was melted, the agitator end of a rotary mixer was inserted into the molten copper and the rotary mixer was actuated to form a vortex in the molten copper. While mixing, 142 grams of powdered activated carbon was introduced to the molten copper. A small quantity of the carbon escaped as it was being added to the molten copper. The powdered activated carbon used was WPH®-M powdered activated carbon, available from Calgon Carbon Corporation of Pittsburgh, Pa. The temperature of the copper and carbon mixture was measured to be about 2335° F.
[0023] A carbon electrode affixed to an arc welder was inserted into the molten copper and carbon mixture. The arc welder was obtained from The Lincoln Electric Company of Cleveland, Ohio. While continuing to mix the carbon into the molten copper, the arc welder was actuated to supply a 135 amp current through the molten copper and carbon mixture. As a result of the current, the carbon was seen as being drawn into the copper and the resulting copper-carbon composition solidified almost instantly, suggesting an endothermic reaction had occurred. Specifically, the temperature of the resulting copper-carbon composition in the crucible quickly dropped from about 2335° F. to below about 1980° F.
[0024] After cooling, the copper-carbon composition was removed from the crucible and observed by the naked eye to exist in a single phase. The cooled copper-carbon composition was then re-melted in the crucible and no phase separation was observed (i.e., a separate carbon only or copper only phase did not occur).
[0025] While the copper-carbon composition was in a molten state, pin samples were taken. The pin samples were quickly and easily rolled out into thin sheets and no fractures were observed along the edges of the thin sheets.
Example 2
[0026] A graphite crucible (electrically coupled to ground) was positioned in an induction furnace. The induction furnace was obtained from the Pillar Induction Company of Brookfield, Wis. The crucible was charged with 20 pounds of C11000 copper obtained from ThyssenKrupp Materials NA.
[0027] Once the copper in the crucible was melted, the agitator end of a rotary mixer was inserted into the molten copper and the rotary mixer was actuated to form a vortex in the molten copper. While mixing, 154 grams of WPH®-M powdered activated carbon was introduced to the molten copper over a period of about 13 minutes. A small quantity of the carbon escaped as it was being added to the molten copper. The temperature of the copper and carbon mixture was measured to be about 2200° F.
[0028] A carbon electrode affixed to a Lincoln arc welder was inserted into the molten copper and carbon mixture. While continuing to mix the carbon into the molten copper, the arc welder was actuated to supply a 230 amp current through the molten copper and carbon mixture. As a result of the current, the carbon was seen as being drawn into the copper to form a copper-carbon composition. Additional heat was supplied during the current supplying step to avoid rapid solidification of the copper-carbon composition and resulting damage to the rotary mixer.
[0029] After cooling, the copper-carbon composition was removed from the crucible and observed by the naked eye to exist in a single phase. The cooled copper-carbon composition was then re-melted in the crucible and no phase separation was observed.
Example 3
Comparative Example
[0030] A graphite crucible (electrically coupled to ground) was positioned in a gas heated furnace. The crucible was charged with 100.2 ounces of 99.9 percent pure copper, which was obtained from ThyssenKrupp Materials NA.
[0031] Once the copper in the crucible was melted, the agitator end of a rotary mixer was inserted into the molten copper and the rotary mixer was actuated to form a vortex in the molten copper. While mixing, 14 grams of exfoliated graphite was introduced to the molten copper. The temperature of the copper and exfoliated graphite mixture was measured to be about 2247° F.
[0032] A carbon electrode affixed to a Lincoln arc welder was inserted into the molten copper and exfoliated graphite mixture. While continuing to mix the exfoliated graphite into the molten copper, the arc welder was actuated to supply a 240 amp current through the molten copper and exfoliated graphite mixture. No temperature drop was observed once the current was supplied.
[0033] After cooling, a copper phase and a carbon phase was observed in the crucible and, therefore, it was believed that the disclosed copper-carbon composition was not formed.
[0034] Accordingly, the disclosed copper-carbon compositions incorporate certain carbonaceous materials into copper metal in substantial quantities to form a single phase material, wherein the carbonaceous material does not phase separate from the copper when the material is cooled and subsequently re-melted.
[0035] Although various aspects of the disclosed copper-carbon composition have been shown and described, modifications may occur to those skilled in the art upon reading the specification. The present application includes such modifications and is limited only by the scope of the claims. | A copper-carbon composition including copper chemically bonded to carbon, wherein the copper and the carbon form a single phase material formed by mixing carbon into molten copper. The single phase material characterized in that it is meltable and that the carbon does not phase separate from the copper when the single phase material is heated to a temperature that melts the copper-carbon composition. | 2 |
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates to a cigar product, and more particularly to a bi-directional multiple-layer pull-in cigar holder.
[0003] 2. Description of the Prior Art
[0004] Referring to FIG. 1 , a conventional cigar holder 10 comprises a first tube 11 and a second tube 12 that are mounted on both ends of a receiving tube 13 . The first tube 11 and the second tube 12 can extend and retract relative to the receiving tube 13 . Each of two opposite ends of the receiving tube 13 is provided with an engaging portion 14 consisting of two half-circle plate 141 . Each of the half-circle plates 141 is formed on an inner surface thereof with a protrusion 142 to be engaged in a through hole in the receiving tube 13 . Each of the first tube 11 and the second tube 12 is provided with a bushing ring 15 at an end thereof for limiting the disengagement of the respective tubes 11 , 12 . However, the respective half-circle plates 141 of the engaging portion 14 are difficult to assemble, thus increasing the assembly time as well as the production cost.
[0005] Additionally, since the first tube 11 and the second tube 12 are mounted on the receiving tube 13 , there are seams on the cigar holder 10 , which will affect the appearance integrity of the cigar holder.
[0006] The present invention has arisen to mitigate and/or obviate the afore-described disadvantages.
SUMMARY OF THE INVENTION
[0007] The primary objective of the present invention is to provide a bi-directional multiple-layer pull-in cigar holder the length of which can be adjusted, increasing the applicability without affecting the appearance integrity.
[0008] To achieve the above objective, a bi-directional multiple-layer pull-in cigar holder in accordance with the present invention comprises:
[0009] two extension tubes;
[0010] at least two circular bases, a first end of each of the two circular bases being connected to a first end of each of the two circular bases, and a second end of each of the two circular bases being formed with plural through holes;
[0011] at least two elastic retaining rings being C-shaped elastic plates, each of the elastic retaining rings including plural protruding portions on an inner surface thereof, the elastic retaining rings being disposed on the respective circular bases, the protruding portions of the elastic retaining rings being engaged in the through holes of the ring grooves;
[0012] a receiving body being in the form of a hollow tube, the two extension tubes being received in the receiving body, the two circular bases being located adjacent to each other, a second end of each of the extension tubes extending out of each of two opposite ends of the receiving body;
[0013] a bottom storage unit being screwed to the second end of a first one of the extension tubes;
[0014] a medium connecting element being in the form of a ring and including a first inner threaded portion and a second inner threaded portion on both ends thereof, the medium connecting element being screwed on a second one of the two extension tube through the first inner threaded portion; and
[0015] a lighter includes an outer threaded portion on an outer surface thereof, the lighter being screwed into the inner threaded portion of the medium connecting element through the outer threaded portion.
[0016] Since the receiving body is mounted outside the two extension tubes, the extension tubes which are used to adjust the length are hid in the receiving body, achieve the objective of length adjustment without affecting the appearance integrity. In addition, the big-area elastic retaining rings can further improve the assembly convenience and reduce the assembly cost.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] FIG. 1 is an exploded view of a conventional cigar holder
[0018] FIG. 2 is an exploded view of a bi-directional multiple-layer pull-in cigar holder in accordance with the present invention;
[0019] FIG. 3 is an assembly view of the bi-directional multiple-layer pull-in cigar holder in accordance with the present invention;
[0020] FIG. 4 is a cross-sectional view showing that the lighter is disassembled from the bi-directional multiple-layer pull-in cigar holder in accordance with the present invention;
[0021] FIG. 5 is a partial enlarged view of FIG. 4 ;
[0022] FIG. 6 is another partial enlarged view of FIG. 4 ;
[0023] FIG. 7 is another partial enlarged view of FIG. 4 ;
[0024] FIG. 8 is a cross-sectional view showing the lighter is assembled on the bi-directional multiple-layer pull-in cigar holder in accordance with the present invention;
[0025] FIG. 9 is a partial enlarged view of FIG. 8 ;
[0026] FIG. 10 is a cross-sectional view showing the extending state of the bi-directional multiple-layer pull-in cigar holder in accordance with the present invention;
[0027] FIG. 11 is a perspective view showing another implementation state of the bi-directional multiple-layer pull-in cigar holder in accordance with the present invention;
[0028] FIG. 12 is another bi-directional multiple-layer pull-in cigar holder in accordance with the present invention;
[0029] FIG. 13 is a partial enlarged view of FIG. 12 ;
[0030] FIG. 14 is another partial enlarged view of FIG. 12 ;
[0031] FIG. 15 is another partial enlarged view of FIG. 12 ; and
[0032] FIG. 16 is a perspective view showing the respective components of the bi-directional multiple-layer pull-in cigar holder in accordance with the present invention are increased in diameter.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0033] The present invention will be clearer from the following description when viewed together with the accompanying drawings, which show, for purpose of illustrations only, the preferred embodiment in accordance with the present invention.
[0034] Referring to FIGS. 1-9 , a bi-directional multiple-layer pull-in cigar holder in accordance with a preferred embodiment of the present invention comprises two extension tubes 20 , at least two circular bases 30 , at least two elastic retaining rings 40 , a receiving body 50 , two end cap rings 60 , a bottom storage unit 70 , a medium connecting element 80 , and a lighter 90 .
[0035] Each of the two extension tubes 20 is formed with a first outer threaded portion 21 and a second outer threaded portion 22 on two opposite ends thereof.
[0036] In the present embodiment, the cigar holder comprises two circular bases 30 , and each of the circular bases 30 is formed in a first end thereof with an inner threaded portion 31 to be screwed on the first outer threaded portion 21 of the respective extension tubes 20 , and a second end of each of the circular bases 30 is formed with a ring groove 32 in an outer surface thereof. Each of the ring grooves 32 is formed with plural through holes 321 . The circular bases 30 are connected to the respective extension tubes 20 by screwing the first outer threaded portions 21 in the inner threaded portions 31 .
[0037] In the present embodiment, the cigar holder in accordance with the present invention comprises two elastic retaining rings 40 which are C-shaped elastic plates. Each of the elastic retaining rings 40 includes plural protruding portions 41 on an inner surface thereof. The elastic retaining rings 40 are received in the respective ring grooves 32 of the circular bases 30 in such a manner that the protruding portions 41 of the elastic retaining rings 40 are engaged in the through holes 321 of the ring grooves 32 .
[0038] The receiving body 50 is in the form of a hollow tube and provided with an outer threaded portion 51 on each of two opposite ends thereof. An extending direction of the receiving body 50 is defined as an axial direction X. The two extension tubes 20 are received in the receiving body 50 . The two circular bases 30 are located adjacent to each other, and the second outer threaded portions 22 of the two extension tubes 20 extend out of the two opposite ends of the receiving body 50 .
[0039] The two end cap rings 60 each include an inner threaded portion 61 on an inner surface of a first end thereof, and a second end of each of the two end cap rings 60 is formed with an inwards-protruding stopping flange 62 . The respective end cap rings 60 are mounted on a second end of the respective extension tubes 20 which extends out of the receiving body 50 in such a manner that the inner threaded portions 61 are screwed on the outer threaded portions 51 . The respective stopping flanges 62 extend in the receiving body 50 .
[0040] The bottom storage unit 70 includes a bottom cover 71 and a bottom storage element 72 . The bottom cover 71 is formed with a first inner threaded portion 711 and a second inner threaded portion 712 in both ends thereof. One of the inner threaded portions 711 , 712 is screwed to the second outer threaded portion of one of the extension tubes 20 , and in the present embodiment, the first inner threaded portion 711 of the bottom cover 71 is screwed on the second outer threaded portion 22 of one of the extension tubes 20 . The bottom storage element 72 has an open end and includes a storage space 721 . The bottom storage element 72 includes an outer threaded portion 722 on the open end thereof. The bottom storage element 72 is screwed to the second inner threaded portion 712 of the bottom cover 71 through the outer threaded portion 722 .
[0041] The medium connecting element 80 is in the form of a ring and includes a first inner threaded portion 81 and a second inner threaded portion 82 on both ends thereof. The medium connecting element 80 is screwed on the second outer threaded portion 22 of the other extension tube 20 through the first inner threaded portion 81 , and the second inner threaded portion 82 is screwed on the outer threaded portion 722 of the bottom storage element 72 .
[0042] The lighter 90 includes an outer threaded portion 91 on an outer surface thereof. The lighter 90 is screwed into the inner threaded portion 82 of the medium connecting element 80 through the outer threaded portion 91 .
[0043] The aforementioned is the summary of the positional and structural relationship of the respective components of the preferred embodiment in accordance with the present invention.
[0044] After the assembly of the above respective components is finished, the respective extension tubes 20 in the receiving body 50 can be used to hold and store the cigar A, and the lighter 90 and the bottom storage unit 70 seal the second ends of the respective extension tubes 20 . The lighter 90 can be taken out when necessary, and when the lighter 90 is taken out, an end of the receiving body 50 is opened to allow the user to take out or put in the cigar A. When the length of the cigar A is greater than a length of the receiving body 50 in the axial direction X, the user can pull the medium connecting element 80 or the bottom storage unit 70 which is screwed to the respective extension tubes 20 , so that the two extension tubes 20 can move away from each other to extend the length of the cigar holder in accordance with the present invention for holding longer cigar A, as shown in FIG. 10 . As known from this, the bi-directional multiple-layer pull-in cigar holder in accordance with the present invention can be adjusted in length by the user, improving its applicability. Since the bi-directional multiple-layer pull-in cigar holder in accordance with the present invention is assembled with the lighter 90 , the user doesn't need to additionally carry a lighter, improving the use convenience.
[0045] To assemble the respective extension tubes 20 , the respective elastic retaining rings 40 will be compressed first, so that the extension tubes 20 can be disposed in the receiving body 50 . When the respective extension tubes 20 are received in the receiving body 50 , the elastic retaining rings 40 will elastically abut against the inner surface of the receiving body 50 due to the fact that the respective elastic retaining rings 40 are fastened on the circular bases 30 , as a result of this, the respective elastic retaining rings 40 can offer a displacement resistance with respect to the receiving body 50 , synchronously avoiding the disengagement of the respective extension tubes 20 .
[0046] Since the elastic retaining rings 40 are C-shaped big-area plates, they can improve the convenience in assembly while offering a more stable resistance, thus ensuring a high operation stability of the cigar holder in accordance with the present invention.
[0047] Further, as shown in FIG. 11 , the lighter 90 can be disassembled for use. After the lighter 90 is disassembled, the bottom storage element 72 of the storage unit 70 can be disassembled from the bottom cover 71 and screwed to the second inner threaded portion 82 of the medium connecting element 80 through the outer threaded portion 722 , so that the bottom cover 71 and the bottom storage element 72 of the bottom storage unit 70 can seal both ends of the cigar holder in accordance with the present invention.
[0048] Furthermore, as shown in FIGS. 12-15 , in another embodiment, the cigar holder in accordance with the present invention can be further provided with an adjusting extension tubes 20 ′ outside each of the extension tubes 20 . The adjusting extension tubes 20 ′ are in structure similar to the extension tubes 20 . Each of the adjusting extension tubes 20 ′ includes a first outer threaded portion 21 ′ and a second outer threaded portion 22 ′ on both ends thereof. The first outer threaded portion 21 ′ of each of the adjusting extension tube 20 ′is screwed to one circular base 30 , and each of the circular bases 30 is also screwed with one elastic retaining ring 40 . The second outer threaded portion 22 ′ of each of the respective adjusting extension tubes 20 ′ is also screwed with one end cap ring 60 . The extension tubes 20 which are engaged to the respective adjusting extension tubes 20 ′ are located at the same end of the respective adjusting extension tubes 20 ′ as the respective circular bases 30 , and the receiving body 50 is mounted outside the respective extension tubes 20 and the respective adjusting extension tubes 20 ′ with the respective circular bases 30 being located adjacent to each other. By such arrangements, it can form a three-layer extension structure, increasing the extension length of the present invention while further improving the applicability of the present invention.
[0049] Moreover, as shown in FIG. 16 , the respective components of the present invention can be increased in diameter such that the cigar holder in accordance with the present invention can hold much more cigars A, further increasing the applicability of the present invention.
[0050] While we have shown and described various embodiments in accordance with the present invention, it is clear to those skilled in the art that further embodiments may be made without departing from the scope of the present invention. | A bi-directional multiple-layer pull-in cigar holder comprises a receiving body mounted on extension tubes which are adapted for adjusting the length of the holder, such that the cigar holder has an extension structure without affecting its appearance, improving the appearance integrity. In addition, with the arrangement of the big-area elastic retaining rings, a right resistance can be offered, improving the assembly convenience while reducing the assembly cost. | 1 |
FIELD OF THE INVENTION
The present invention relates to novel diorganopolysiloxane compositions and cured products therefrom, wherein aromatic polyimide polymer or polybenzobisoxazole polymer is an essential component. The invention further relates to methods for the preparation of the compositions.
BACKGROUND OF THE INVENTION
Fiber-reinforced composites are one example of the conversion of polymer materials into composites with the goal of application as structural materials that must exhibit high stiffness and high strength. Molecular composites have been proposed for the purpose of realizing the concept of macroscopic fiber-reinforced composites on the molecular level (see, for example, Motowo Takayanagi, Kobunshi, volume 33, page 615 (1984), and Rikio Yokota, Kino Zairyo (Functionand Materials), October issue, page 22 (1988)). Molecular composites consist of polymer with a rigid linear main chain that is molecularly dispersed in a flexible polymer matrix. Since the rigid linear polymer has a very large aspect ratio in the absence of aggregation, a reinforcing activity close to that of a fiber-reinforced composite can theoretically be obtained. Moreover, high-performance materials can be expected because, unlike fibers, there are also no defects at the level of the individual molecules.
Generally, however, the molecular dispersion of rigid linear polymers in flexible polymers is problematic. The various attempts at solving this problem have consisted of for example,
(i) the synthesis of a block copolymer of poly(p-phenylene terephthalamide) (=rigid linear polymer) and nylon 6 (=flexible polymer) followed by dispersion of this block copolymer in nylon 6 (Motowo Takayanagi et al J. Macromol. Sci.-Phys., volume B17, page 591 (1980)),
(ii) metalation of poly(p-phenylene terephthalamidei) (Motowo Takayanagi et al., J. Appl. Polym. Sci., volume 29, page 2547 (1984)),
(iii) polymerization of acrylamide by metalation-generated poly (p-phenylene-terephthalamide) anion with the simultaneous production of a nylon 3 matrix and nylon 3-grafted poly(p-phenylene terephthalamide) (D. R. Moore et al., J. Appl. Polym. Sci., volume 32, page 6299 (1986)),
(iv) blending the polyamic acid precursors of an wholly-aromatic rigid linear polyimide and a polyimide that contains flexible groups in its main chain and then thermally imidizing this blend (Itaru Mira, Kemikaru Enjiniyaringu [Chemical Engineering], August issue, page 69 (1990)),
(v) conducting polymerization to give rigid linear poller in a solution of matrix poller (Kohei Sanui et al, J. Polym.
Sci.: Part A: Polym. Chem., volume 31, page 597 (1993), and so forth), and
(vi) utilization of hygrogen bonds (J. C. Painter et al., ACS Polym. Prepr., volume 32, number 1, page 208 (1991)).
On the other hand, since polydimethylsiloxanes have a low intermolecular cohesive energy, the pure rubber has a low mechanical strength and is typically reinforced by filling with reinforcing silica (see Kunio Itoh (ed.), Shirikoon Handobukku [Silicone Handbook], Nikkan Kogyo Shinbunsha (1990), etc.).
The above-mentioned molecular composites are concerned mainly with plastics, and the use of silicone rubber as a matrix has not been reported up to now. If a rigid linear polymer could be dispersed in a diorganopolysiloxane matrix, it would be possible to provide a novel reinforcing method for silicone rubbers. However, rigid linear polymers and polysiloxanes are inherently incompatible.
SUMMARY OF THE INVENTION
An object of the present invention is to provide rigid linear polymers having compatibility with polysiloxanes and therefore to provide compositions that contain both types of polymers, as well as cured products therefrom. The aforesaid object is achieved by the disclosure of diorganopolysiloxane compositions comprising:
(i) 1 to 99.99 weight % of a diorganopolysiloxane
(ii) 0.01 to 99 weight % of a organopolysiloxane-grafted rigid linear aromatic polymer selected from the group consisting of organopolysiloxane-grafted polyimides and organopolysiloxane-grafted polybenzobisoxazoles.
The present invention also teaches a method for preparing the above compositions that contain polysiloxane and aromatic polyimide or polybenzobisoxazole (i.e., rigid linear polymers) and a method for preparing the cured products of such compositions.
The method of the present invention thus makes possible the preparation of molecular composites comprising the dispersion of rigid linear aromatic polymer in diorganopolysiloxane. This provides a novel reinforcing method for both crosslinked and uncrosslinked silicone materials.
The present invention has been described in Japanese Application for Patent Hei 5-210248 and Hei 5-210525, filed Aug. 25, 1993, the full disclosures of which are hereby incorporated by reference.
DETAILED DESCRIPTION OF THE INVENTION
Preferred organopolysiloxane-grafted aromatic polyimides suitable for use in the present invention comprise copolymers that are composed of units with formulas (I) and (II) ##STR1## wherein the unit (I)/unit (II) molar ratio is in the range of 100/0 to 1/99. In these formulas, A 1 denotes a tetravalent aromatic group and A 2 denotes a divalent aromatic group on which there is bonded one or two organopolysiloxanes with formula (III) per unit with formula (I). ##STR2## In the above formula, R 1 denotes a divalent organic group, R 2 through R 6 denote monovalent organic groups which may be the same or different, and n is an integer with a value of 1 or greater.
A 3 comprises at least 1 selection from reactive side chain-free divalent aromatic groups and reactive side chain-substituted divalent aromatic groups, wherein the molar ratio of reactive side chain-free divalent aromatic groups to reactive side chain-substituted divalent aromatic groups is in the range of 100/0 to 0/100.
This aromatic polyimide must have a degree of polymerization (DP) based on units (I) and (II) off at least 5. A reinforcing activity is not exhibited in the corresponding molecular composites when the DP is 4 or less.
The polyamic acid and derivatives thereof that are the precursor polymers for the subject polyimides comprise copolymers whose units can be expressed by formulas (IV) and (V) ##STR3## in which A 1 , A 2 , and A 3 are the same as described above, and R 7 denotes hydroxyl, alkoxy, dialkylamino, or trialkylsiloxy.
The tetravalent aromatic group denoted by A 1 in the above formulas is exemplified by C 6 to C 30 tetravalent groups such as ##STR4## and combinations of these skeletons; however, the present invention is not limited to these examples.
The divalent aromatic group moiety of A 2 (exclusive of the side chains) and the divalent aromatic group moiety of A 3 (exclusive of any reactive substituents) are exemplified by ##STR5## and by combinations of the preceding (groups having 6 to 60 carbon atoms are preferred). However, the present invention is not limited to these examples.
The divalent organic group indicated by R 1 in formula (III) is exemplified by alkylene, oxyalkylene, phenylenealkylene, phenyleneoxyaikylene, etc.; however, oxyalkylene is preferred from the standpoint of ease of acquisition. R 2 through R 6 indicate monovalent organic groups, and examples here include alkyl groups such as methyl, ethyl, propyl, octyl, etc.; substituted alkyl groups such as 2-phenylethyl, 2-phenylpropyl, 3,3,3-trifluoropropyl, etc.; aryl groups such as phenyl, etc.; and substituted aryl groups such as tolyl, etc. In regard to R 6 , methyl, n-butyl, sec-butyl, tert-butyl, and phenyl are desirable from the standpoint of ease of acquisition of starting material for the hydroorganopolysiloxane precursor with formula (VI) ##STR6## in which R 2 through R 6 have the same definitions as above and the subscript n is a positive integer, preferably 1 to 5,000.
The reactive side chain-containing divalent aromatic groups encompassed by A 3 contain one or more groups --R 8 Q bonded as substituents on aromatic groups as described above for reactive side chain-free A 3 . R 8 denotes a divalent organic group and is exemplified by alkylene, oxyalkylene, phenylenealkylene, phenyleneoxyalkylene, etc.; however, oxyalkylene is preferred from the standpoint of ease of acquisition. Q is exemplified by vinyl, acryloyl, methacryloyl, hydroxyl, amino, carboxyl, epoxy, SiH, SiOH, alkoxysilyl, etc. Vinyl, acryloyl, and methacryloyl, are preferred from the standpoint of ease of synthesis.
The polyamic acids and derivatives thereof with formulas (IV) and (V) can be prepared as follows. For example, the polyamic acid (R 7 =OH) is obtained by reacting equimolar amounts of aromatic tetracarboxylic dianhydride with formula (VII) ##STR7## wherein A 1 is defined as above, and aromatic diamino compounds with formulas (VIII) and (IX)
H.sub.2 N--A.sup.2 --NH.sub.2 (VIII)
H.sub.2 N--A.sup.3 --NH.sub.2 (IX)
where A 2 and A 3 are defined as above. Polyamic acid derivatives in which R 7 =trialkylsiloxy can be obtained by reacting tetracarboxylic dianhydride (VII) with compounds prepared by the trialkylsilylation of diamino compounds (VIII) and (IX). For R 7 =alkoxy, dialkylamino group, and so forth, the particular derivative is obtained by reacting the aromatic tetracarboxylic acid derivative with formula (X) ##STR8## where R 7 and A 1 are defined above, with aromatic diamino compounds with formulas (VIII) and (IX).
The compounds with formula (VIII), which are polysiloxane chain-containing macromonomers, can be synthesized, for example, by first synthesizing a dinitro compound-containing organopolysiloxane by running a catalyzed hydrosilylation reaction between hydrogen-terminated organopolysiloxane (VI) and a compound comprising the di-nitro-substituted aromatic moiety of A 2 on which one or two organic groups having terminal ethylenic unsaturation are bonded as substituents. The synthesis is concluded by reduction of the nitro groups.
Methods are known for the preparation of hydrogen-terminated organopolysiloxane (VI).
The substituents exhibiting terminal ethylenic unsaturation on the dinitro compound are exemplified by --CH═CH 2 , --CH 2 CH═CH 2 , --CH 2 CH 2 CH═CH 2 , --CH(CH 3 )CH═CH 2 , --(CH 2 ) 6 CH═CH 2 , --OCH═CH 2 , --OCH 2 CH═CH 2 , --OCH 2 CH 2 CH═CH 2 , --OCH(CH 3 )CH═CH 2 , --O(CH 2 ) 6 CH═CH 2 , and so forth. Preferred on the basis of ease of starting material acquisition are --OCH═CH 2 , --OCH 2 CH═CH 2 , --OCH 2 CH 2 CH═CH 2 , --OCH(CH 3 )CH═CH 2 , --O(CH 2 ) 6 CH═CH 2 , and so forth. These compounds are generally not available commercially, but they can be synthesized, for example, by the procedure provided below in the reference examples.
The subject hydrosilylation reaction is run in the presence of catalyst and is preferably run in solvent. A platinum catalyst is most commonly used as the catalyst, for example, chloroplatinic acid, platinum-divinyltetramethyldisiloxane complexes, Pt/C, and so forth, but transition metal catalysts such as (Ph 3 P) 3 RhCl (Ph=phenyl), (Ph 2 PH) 3 RhCl, (Ph 3 P) 3 (CO)RhH, and other transition metal catalysts containing Co(I), Pd(II), and Ru(II) may also be employed. Suitable catalyst additions generally correspond to approximately 1/10 4 to 1/10 2 moles per 1 mole carbon-carbon double bond. Usable solvents are exemplified by aromatic hydrocarbon solvents such as benzene, toluene, xylene, and so forth; aliphatic hydrocarbon solvents such as hexane, heptane, and so forth; ether solvents such as diethyl ether, tetrahydrofuran, and so forth; alcohol solvents such as methanol, ethanol, propanol, and so forth; ketone solvents such as acetone, methyl ethyl ketone, and so forth; ester solvents such as ethyl acetate, butyl acetate, and so forth; halohydrocarbon solvents such as chloroform, trichloroethylene, carbon tetrachloride, and so forth; and dimethylformamide, N,N-dimethylacetamide dimethyl sulfoxide, and so forth. The reaction is run at temperatures of 0° C. to 200° C., and preferably 40° C. to 110° C., in a dry inert atmosphere. However, the introduction of small quantities of oxygen may be advantageous depending on the particular catalyst used.
The nitro groups in the aforementioned dinitro compoun-dcontaining organopolysiloxane can be reduced to amino groups by, for example, catalytic reduction with hydrogen using a catalyst such as platinum, Raney nickel, platinum/carbon, palladium/carbon, rhodium/alumina, platinum sulfide/carbon sulfide, and so forth. The reaction is preferably run in a solvent, and usable solvents are exemplified by the various solvents listed above and by mixtures of said solvents. The reaction temperature is preferably in the range from room temperature to the reflux temperature of the solvent. The method of reduction is not limited to the method outlined above.
The organopolysiloxane chain of the aromatic diamino compound-containing macromonomer (VIII) may also carry a reactive group or groups capable of bonding with the matrix diorganopolysiloxane. For example, instead of using the hydrogen-terminated organopolysiloxane (VI), organopolysiloxane that has the hydrosilyl group at one terminal and a reactive group at the other terminal can be prepared by known methods and the synthesis can then be run using this organopolysiloxane. The reactive group must not participate in the hydrosilylation or nitro group reduction reactions described above or in any reaction in the polyamic acid polymerization process. An example of such groups is alkoxysilyl.
Among the aromatic diamino compounds (IX), compounds bearing reactive groups on A 3 are not generally commercially available. However, compounds of this type can be synthesized by, for example, first protecting the amino groups on an aromatic diaminohydroxy compound, introducing olefin through an ether synthesis between the hydroxy group and a halogenated olefin according to the procedure described in the reference examples below, and then deprotecting the amino groups.
The silylation of the aromatic diamino compounds with formulas (VIII) and (IX) is accomplished using a silylating agent. The silylating agent is exemplified by trialkylhalosilanes such as trimethylchlorosilane, triethylchlorosilane, triphenylchlorosilane, methyldiethylbromosilane, and so forth, and by nitrogenous silylating agents such as hexamethyldisilazane, N,N-diethylaminotrimethylsilane, N, O-bis (trimethylSilyl) carbamate, N-trimethylsilylimidazole, and so forth. If a trialkylhalosilane is used, the addition of a base is then preferred in order to neutralize the hydrogen halide produced as by-product. A catalyst such as trimethylchlorosilane, ammonium sulfate, and so forth, may be added when a nitrogenous silylating agent is used. The silylation reaction may be run, in the absence of solvent or in the various solvents listed above excluding alcohols. The reaction temperature is 0° C. to 200° C. and preferably 20° C. to 140° C.
The aromatic tetracarboxylic acid derivatives with formula (X) are obtained by reacting an aromatic tetracarboxylic dianhydride (VII) with an alkyl alcohol or dialkylamine, to give an aromatic tetracarboxylic acid derivative with formula (XI) ##STR9## wherein A 1 and R 7 have the same meaning as described above, and by then reacting (XI) with inorganic halide.
The inorganic halide is exemplified by phosphoryl chloride, thionyl chloride, phosphorus pentachloride, phosphorus trichloride, and so forth. Thionyl chloride is preferred because it has a low boiling point and because the corresponding by-products are gases or low-boiling compounds, which facilitate product recovery. The reaction with inorganic halide (preferably thionyl chloride) can be run without solvent or in the solvents listed above. Zinc chloride, pyridine, iodine, triethylamine, etc., can be used as catalyst, but the use of catalyst may be omitted. The reaction temperature is -50° C. to 140° C. and preferably -30° C. to 120° C.
The polyamic acids and derivatives thereof as described above are preferably synthesized in a dry inert gas atmosphere. The reaction may be run without a solvent, but is preferably carried out in a solvent. Usable solvents are exemplified by the various solvents listed above and by their mixtures. The reaction temperature is preferably -50° C. to 100° C., and is even more preferably in the range of 0° C. to 50° C.
With reference to general formulas (I) through (XI), highly suitable examples of aromatic polyimides for the present invention are as follows:
unit (I)/unit (II) molar ratio =100/0 to 30/70,
n=3 to 1,000,
R 1 =C 2 to C 20 oxyalkylene,
R 2 through R 5 =methyl or phenyl, and
R 6 =methyl, n-butyl, sec-butyl, tert-butyl, or phenyl.
The following may be cited as optimal examples of A 1 , A 2 , and A 3 from the standpoint of ease of acquisition: ##STR10## wherein Z is a monovalent polysiloxane with formula (III) and m is 0 or 1, ##STR11## where R 8 =oxyalkylene and Q=vinyl, and reactive side chain-free divalent aromatic group/reactive side chain-substituted divalent aromatic group molar ratio in A 3 =100/0 to 50/50.
Preferred organopolysiloxane-grafted aromatic polybenzobisoxazole used in the present invention comprise units with formulas (XII) and (XIII) ##STR12## wherein the unit (XII)/unit (XIII) molar ratio is 00/0 to 1/99 and A 1 , A 2 and A 3 have their previously defined meanings.
This aromatic polybenzobisoxazole must have a degree of polymerization based on units (XII) and (XIII) of at least 5. A reinforcing activity is not exhibited in the corresponding molecular composites when the DP is 4 or less.
The polyhydroxyamide and derivatives thereof that are precursor polymers for the subject aromatic polybenzobisoxazoles comprise copolymers whose units are expressed by formulas (XIV) and (XV) ##STR13## in which A 1 , A 2 , and A 3 are the same as described above, and R 9 indicates H or a trialkylsilyl group.
The silylated polyhydroxyamides (R 9 =trialkylsilyl) are obtained by reacting equimolar amounts of aromatic dicarboxylic acid halides with formulas (XVI) and (XVII)
XCO--A.sup.2 --COX (XVI)
XCO--A.sup.3 --COX (XVI)
wherein X denotes a halogen group, preferably the chlorine atom, and A 2 and A 3 have the same meanings as described above, and silylated aromatic diaminodihydroxy compounds with formula (XVIII) ##STR14## wherein R 10 denotes an alkyl group, and A 1 has the same meaning as described above. Polyhydroxyamides in which R 9 is H are obtained by hydrolyzing these silylated polyhydrbxyamides.
The compounds with formula (XVI), which are macromonomers that carry aromatic dicarboxylic acid halide, are prepared by first synthesizing the corresponding aromatic dicarboxylic acid-functionalized organopolysiloxane macromonomer by running a catalyzed hydrosilyiation reaction between hydrogen-terminated organopolysiloxane (VI) and a compound prepared by protecting the carboxyl groups on a compound comprising the di-carboxyl-substituted aromatic group moiety of A 2 on which one or two organic groups having terminal ethylenic unsaturation are bonded as substituents. This step concludes with deprotection of the carboxyl groups. The carboxyl groups are then silylated and the resulting compound is reacted with inorganic halide. If the carboxyl groups on the aromatic dicarboxylic acid carrying terminal ethylenically unsaturated organic groups (i. e., a starting compound) have been protected by silylation, the silyl dicarboxytate macromonomer produced by the hydrosilylation reaction with polysiloxane (VI) may be directly reacted with inorganic halide.
The thermal ethylenically unsaturated substituents on the above-mentioned aromatic dicarboxylic acid compounds are the same as those on the dinitro compounds used in the polyamic acid synthesis described above. These compounds are not generally commercially available, but they can be synthesized by, for example, the procedures described below in the reference examples.
The protection step of the carboxyl group that sets up the hydrosilylation reaction is exemplified by esterification with methyl, ethyl, methoxymethyl, tert-butyl, benzyl, beta-p-toluenesulfonylethyl, trialkylsilyl, and so forth. Trialkylsilyl esterification is preferred for the corresponding ease of removal of the protective groups from the product. This silylation reaction is run in the same manner as described above. The hydrosilylation reaction is also the same as described above. Furthermore, the silylation of the carboxyl groups on the aromatic dicarboxylic acid-functionalized organopolysiloxane macromonomer and the reaction with inorganic halide are also the same as described above. The reaction between inorganic halide and carboxylic acid ordinarily produces acid, which induces main chain scission reactions in polysiloxanes. However, if the reaction with inorganic halide is run after the carboxyl groups have been silylated, the by-products are trialkylhalosilanes, etc., and the acid halide can in this manner be synthesized without causing main chain scission reactions in the polysiloxane.
The organopolysiloxane chain in the aromatic dicarboxylic acid halide-functionalized macromer (XVI) may also carry reactive groups capable of bonding with the matrix diorganopolysiloxane. Synthesis can be accomplished in the same manner as described above through the use of organopolysiloxane that has a hydrosilyl group at one terminal and a reactive group at the other terminal. Said reactive group must not participate in the above-mentioned hydrosilylation reaction or in any reaction in the reaction sequence involving the aforementioned inorganic halide. Examples of such groups include alkoxysilyl groups, etc.
Among the aromatic dicarboxylic acid halides with formula (XVII), aromatic dicarboxylic acid halides that carry reactive groups on A 3 are not generally commercially available. However, as shown in the reference examples below, such compounds can be obtained, for example, by reacting a terminal olefin-substituted aromatic dicarboxylic acid with inorganic halide as described above. In this case, of course, silylation of the carboxyl groups is unnecessary.
Examples of the silylated aromatic diaminodihydroxy compounds (XVIII) include
1,5 -bis(trimethylsilylamino)-2,4-bis(trimethylsiloxy)benzene,
3,3'-bis(trimethylsilylamino)-4,4'-bis(trimethylsiloxy)biphenyl,
2,3'-bis(trimethylsilylamino)-3,4'-bis(trimethylsiloxy)biphenyl,
bis(3-trimethylsilylamino-4-trimethylsiloxyphenyl)methane,
bis(3-trimethylsilylamino-4-trimethylsitoxyphenyl)ether,
bis(3-trimethylsilylamino-4-trimethylsiloxyphenyl)ketone,
2,2-bis(3-trimethylsilylamino-4-trimethylsiloxyphenyl)propane,
2,2-bis(3-trimethylsilylamino-4-trimethylsiloxyphenyl)hexafluoro propane, bis(3-trimethylsilylamino-4-trimethylsiloxyphenyl) sulfone, 2,7-bis(trimethylsilylamino)-3,6-bis(trimethylsiloxy)naphthalene,1,6-bis(trimethylsilylamino)-2,5-bis(trimethylsiloxy)naphthalene, 1,4-bis(trimethylsilylamino)-5,8-bis(trimethylsiloxy)naphthalene, 2,7-bis(trimethylsilylamino) 3,6-bis(trimethylsiloxy)anthracene, 1,6-bis(trimethylsilylamino)-2,5-bis(trimethylsiloxy)anthracene, 3,10-bis(trimethylsilylamino)-4,9-bis(trimethylsiloxy)perylene, and
2,6-bis(trimethylsilylamino)-3,5-bis(trimethylsiloxy)pyrazine.
However, the present invention is not limited to these compounds, and mixtures of these compounds may also be used. These compounds are not generally commercially available; however, said compounds can be synthesized from the corresponding diaminodihydroxy compounds, as will be described later in the reference examples.
The silylated polyhydroxyamide is obtained by reacting equimolar amounts of dicarboxylic acid halide (XVI) and (XVII) with compound (XVIII) in a dry inert atmosphere. This reaction may be run without a solvent, but is preferably run in a solvent. Usable solvents are exemplified by the various solvents mentioned above (excluding alcohols) and their mixtures. The reaction temperature is preferably -70° C. to 100° C., and is even more preferably -40° C. to 40° C.
The silylated polyhydroxyamide can be hydrolyzed to give the polyhydroxyamide by pouring the reaction solution into an alcohol such as methanol, etc., or by stirring the solvent-free silylated polyhydroxyamide for several hours in an alcohol such as methanol.
With reference to formulas (XII) and (XIII), highly suitable examples of polybenzobisoxazoles for the present invention are as follows:
unit (XII)/unit (XIII) molar ratio =100/0 to 30/70,
n=3 to 1,000,
R 1 =C 2 to C 20 oxyalkylene,
R 2 through R 5 =methyl or phenyl,
R 6 =methyl, n-butyl, sec-butyl, tert-butyl, or phenyl, ##STR15## wherein, Z is monovalent polysiloxane with formula (III) and mis 1 or 2, ##STR16## where R 8 =oxyalkylene and Q=vinyl, and
reactive side chain-free divalent aromatic group/reactive side chain-substituted divalent aromatic group molar ratio in A 3 =100/0 to 50/50.
The diorganopolysiloxane of the present invention is expressed by the formula R a R' b SiO.sub.(4-a-b)/2 in which 1.9≦a+b≦2.2 and 0≦b≦0.2; R indicates a C 1 to C 5 alkyl group (optimally methyl), a substituted alkyl group (optimally 2-phenylethyl, 2-phenylpropyl, or 3,3,3-trifluoropropyl), an aryl group (optimally phenyl), or a substituted aryl group (optimally tolyl); and R' indicates an ethylenically unsaturated organic group (optimally vinyl) or a reactive group (optimally silanol, alkoxysilyl, hydroxyl, or mercapto). The viscosity of this compound is 20 to 5,000,000 cS at 25° C.
In order to form the compositions of the invention, the organopolysiloxane-grafted rigid linear aromatic polymer may be blended with the matrix organopolysiloxane, for example, by kneading or melt blending using a kneader, or by solution blending; the latter consists of removal of the solvent from a solution containing both components. Although pollers with highly linear conformations can be expected to exhibit comparatively stronger reinforcing activities even among the rigid linear aromatic polymers under consideration, such polymers may not have a solubility adequate to support solution blending even after the introduction of organopolysiloxane side chains. If in such cases a solvent-soluble precursor polymer exists for the rigid linear aromatic polymer, a blend can first be prepared by the solution method between the organopolysiloxane-grafted precursor polymer and the matrix organopolysiloxane and the matrix-dispersed precursor polymer can thereafter be converted into the rigid linear polymer.
The composition of the present invention is preferably obtained by preparing a homogeneous organic solvent solution of the diorganopolysiloxane plus precursor polymer as described above, removing the organic solvent, and then inducing thermal cyclization of the precursor polymer dispersed in the polysiloxane matrix. The organic solvent may be any solvent that is capable of dissolving both the organopolysiloxane-grafted precursor polymer and the diorganopolysiloxane. Examples of such organic solvents include tetrahydrofuran and mixtures of tetrahydrofuran with a polar solvent such as dimethylacetamide. The imidization of the polyamic acid and derivatives thereof is accomplished by heating to a temperature of 100° C. to 400° C. (preferably 150° C. to 350° C.). The thermally-induced cyclization of the polyhydroxamides and silylated polyhydroxyamides into polybenzobisoxazoles is accomplished by heating to a temperature of 100° C. to 400° C. (preferably 200° C. to 350° C.). In both cases, the atmosphere may be ordinary air or an inert gas, and the pressure may be reduced if desired. The composition should contain about 0.01 to about 99 weight % organopolysiloxane-grafted aromatic polyimide or organopolysiloxane-grafted polybenzobisoxazole. Little effect from filling is obtained at lower contents, while at larger contents the composition becomes indistinguishable from the organopolysiloxane-grafted aromatic polyimide or organopolysiloxane-grafted polybenzobisoxazole itself.
It is also contemplated herein that the organopolysiloxane side chains of the instant organopolysiloxane-grafted rigid linear aromatic polymers may contain functional groups capable of reacting with the diorganopolysiloxane matrix. That is, some of the groups R 2 through R 6 in formula (III) may be selected from groups such as vinyl, hydroxyl, alkoxysilyl and hydroxysilyl, inter alia. These reactive groups and/or those reactive groups present in above mentioned group A 3 allow the instant organopolysiloxane-grafted rigid linear aromatic polymers to be cured by methods well known in the art.
Rubbery elastic material can be obtained from the organopolysiloxane-grafted rigid linear aromatic polymer and diorganopolysiloxane of the present invention through the use of curing agents. Usable curing methods include organoperoxide-mediated crosslinking, condensation reaction-based crosslinking, addition reaction-based crosslinking, etc. The selection of desirable combinations of curing agent and/or curing catalyst and functional groups on the diorganopolysiloxane base polymer as a function of the curing mechanism is well known in the art (see Kunio Itoh (ed.), Shirik oon Handobukku (Silicone Handbook), Nikkan Kogyo Shinbunsha (1990), etc.). In addition to the reinforcing agent according to the present invention, the diorganopolysiloxane matrix may contain any other known reinforcing agent.
Cured diorganopolysiloxane products containing organopolysiloxane-grafted aromatic polyimide or organopolysiloxane-grafted polybenzobisoxazole are obtained by preparing a homogeneous organic solvent solution of the precursor polymer and diorganopolysiloxane in the same manner as described above, curing the matrix diorganopolysiloxane, either after removal of the organic solvent or in parallel with removal of the organic solvent, and then inducing cyclization of the precursor polymer by heating in the same manner as described above. For the same reasons as described above, subject cured products should contain about 0.01 to about 99 weight % organopolysiloxane-grafted aromatic polyimide or organopolysiloxane-grafted polybenzobisoxazole.
In the absence of the organopolysiloxane side chains, macroscopic phase separation will occur when the solvent is removed from the solution containing the diorganopolysiloxane, even if the precursor polymer is soluble in said solvent. However, use of the methods described above makes it possible to blend strongly reinforcing high-molecular-weight aromatic polyimide or polybenzobisoxazole with a diorganopolysiloxane and also makes possible dispersion of the former in the diorganopolysiloxane matrix at the molecular level. Moreover, even in those cases where curing of the matrix is impaired by the loss of composition fluidity that arises as a consequence of the use of the strongly reinforcing high-molecular-weight aromatic polyimide or polybenzobisoxazole, a crosslinked diorganopolysiloxane molecular composite, in which the aromatic polyimide or polybenzobisoxazole is dispersed at the molecular level, can still be obtained by conducting the cure in the solution and removing the solvent as curing proceeds.
EXAMPLES
The invention will be described in greater detail below using reference examples, working examples, and comparative examples. However, the present invention is in no way limited by these examples. All amounts and percentages are on a weight basis unless indicated to the contrary
Reference Example 1
Synthesis of 2-(3-butenyloxy)-4,4'-dinitrobiphenyl
A mixture of 15.0 mL water and 11.0 mL concentrated sulfuric acid was added to 13.0 g of 4,4'-dinitro-2-aminobiphenyl, and the resulting mixture was stirred for 2 hours while heating, whereupon 26.5 g of crushed ice was added. On an ice bath, an aqueous solution of 3.51 g of sodium nitrite was added dropwise to the aforementioned mixture; the resulting system was mixed for 10 minutes and subsequently allowed to stand at quiescence for several minutes. The reaction mixture was then added dropwise to a boiling solution that had been prepared by adding 33.4 mL concentrated sulfuric acid to 25 mL of water. Boiling was continued for 5 minutes, after which the mixture was poured into a beaker on an ice bath. The filter cake afforded by suction filtration was purified by column chromatography to give 10.9 g of 4,4'-dinitro-2-hydroxybiphenyl as a yellowish brown powder.
Next, 10.4 g of the 4,4'-dinitro-2-hydroxybiphenyl thus obtained was dissolved in 95 mL dry acetone. 5.52 g of potassium carbonate and 7.56 g of 4-bromo-1-butene were added, and the resulting mixture was heated under reflux for 71 hours. Workup by the usual methods gave 5.20 g of 2-(3-butenyloxy)-4,4'-dinitrobiphenyl as a light yellow powder.
Reference Example 2
Synthesis 1 of 4,4'-dinitrobiphenyl-containing polysiloxane
2.52 g of the 2-(3-butenyloxy)-4,4'-dinitrobiphenyl synthesized in Reference Example 1 was dissolved in 80 mL of dry toluene. To this was first added 100 microliters of a 3% chloroplatinic acid 2-propanol solution, and a solution in 20 mL dry toluene of 7.88 g of hydrogen-terminated polysiloxane (average value of n: 14.4) with the formula ##STR17## was then added dropwise. Heating was continued for 4 hours at 100° C. Purification by column chromatography yielded 8.68 g of the 4,4'-dinitrobiphenyl-terminated polysiloxane as a waxy light yellow solid.
Reference Example 3
Synthesis 2 of 4,4'-dinitrobimhenyl-containing polysiloxane
6.29 g of 4,4'-dinitrobiphenyl-terminated polysiloxane (average value of n: 46.2) was synthesized by the procedure of Reference Example 2.
Reference Example 4
Synthesis 1 of 4,4'-diaminobiphenyl-containing polysiloxane
270 mg of 5%-Pd/C was suspended in 14 mL of a 1:1 mixed solvent of ethanol and benzene. While passing hydrogen through the system, a solution was added that consisted of 3.21 g of the 4,4'-dinitrobiphenyl-containing polysiloxane (average value of n: 14.4) synthesized in Reference Example 2 dissolved in 14 mL of the same mixed solvent. Hydrogen was injected into the system for 3 hours while stirring. The catalyst was then filtered off and the solvent was distilled under reduced pressure to give 3.00 g of the 4,4'-diaminobiphenyl-terminated polysiloxane as a viscous yellow liquid.
Reference Example 5
Synthesis 2 of 4,4'-diaminobiphenyl-containing polysiloxane
2.25 g of 4,4'-diaminobiphenyl-terminated polysiloxane (average value of n: 46.2) was synthesized by the procedure of Reference Example 4 from the 4,4'-dinitrobiphenyl-containing polysiloxane synthesized in Reference Example 3.
Reference Example 6
Synthesis 1 of polysiloxane-grafted polyamic acid
1.79 g of the 4,4'-diaminobiphenyl-containing polysiloxane (average value of n: 46.2) synthesized in Reference Example 5 was dissolved in 9 mL dry tetrahydrofuran. 0.112 g of pyromellitic dianhydride was added, and the resulting mixture was stirred at room temperature. A glass plate was coated with the polyamic acid solution thus produced, and the solvent was then removed at 30° C. under reduced pressure to give a polyamic acid film.
Reference Example 7
Synthesis of polysiloxane-grafted polyimide
Operating in an argon atmosphere, the polyamic acid film produced in Reference Example 6 was heated for 20 minutes at 60° C., 20 minutes at 100° C., and 2 hours at 200° C. to give a polysiloxane-grafted polyimide film.
Reference Example 8
Synthesis 2 of polysiloxane-grafted polyamic acid
0,201 g of the 4,4'-diaminobiphenyl-containing polysiloxane (average value of n: 14.4) synthesized in Reference Example 4 and 0.496 g of the 4,4'-diaminobiphenyl-containing polysiloxane (average value of n: 46.2) synthesized in Reference Example 5 were dissolved in 5 mL dry tetrahydrofuran. 0.062 g of pyromellitic dianhydride was added, and the resulting mixture was stirred at room temperature. A glass plate was coated with the polyamic acid solution thus produced, and the solvent was removed at 30° C. under reduced pressure to give a polyamic acid copolymer film having two types of side chains with different lengths (ratio of the two types of units: 1:1).
Examples 1 through 14
Polysiloxane-grafted polyimide/polysiloxane blends
Polysiloxane-grafted polyamic acid synthesized according to Reference Example 6 or 8 and polydimethylsiloxane with an average degree of polymerization of 140 or 600 were dissolved in tetrahydrofuran, and the clear solution thus obtained was coated on a glass plate. The solvent was then removed at 30° C. under reduced pressure to give a blend of the polysiloxane-grafted polyamic acid and polydimethylsiloxane. The blend was heated in an argon atmosphere for 20 minutes at 60° C., 20 minutes at 100° C. and 2 hours at 200° C. to give a blend of polysiloxane-grafted polyimide and polydimethylsiloxane. The production of the polyimide was confirmed from the IR spectrum. The characteristic polyimide absorptions at 1780, 1730, 1380, and 725 cm -1 were observed, and the absorptions attributable to the amic acid had disappeared. The results are reported in Table 1.
Despite the fact that the polysiloxane-grafted polyimide prepared in Reference Example 7 was a rubber and the polydimethylsiloxanes used in the blends were liquids, the blends obtained in Examples 3, 4, 5, 9, and 10 were solids, and a reinforcement of the polydimethylsiloxanes was thus observed.
TABLE 1______________________________________ content of content of average grafted polyimideexample value of polyimide main chain compati-number n PDMS (weight %) (weight %) bility______________________________________1 46.2 A 10.4 1.0 good2 46.2 A 20.8 2.0 good3 46.2 A 37.5 3.6 good4 46.2 A 46.9 4.5 good5 46.2 A 69.8 6.7 good6 46.2 B 9.8 0.94 good7 46.2 B 17.7 1.7 good8 46.2 B 31.3 3.0 good9 46.2 B 46.9 4.5 good10 46.2 B 75.0 7.2 good11 14.4/46.2 A 56.6 7.7 good12 14.4/46.2 B 14.7 2.0 good13 14.4/46.2 B 28.7 3.9 good14 14.4/46.2 B 58.1 7.9 good______________________________________ PDMS = polydimethylsiloxane
In the preceding table, A denotes polydimethylsiloxane with an average degree of polymerization of 140, and B denotes polydimethylsiloxane with an average degree of polymerization of 600. An average value for n of 14.4/46.2 indicates the use of polyamic acid carrying side chains with respective degrees of polymerization of 14.4 and 46.2 at a ratio of 1:1.
Reference Example 9
Synthesis of side chain-free polyamic acid
1.00 g of 4,4'-diaminobiphenyl ether was dissolved in 17 mL of dry N,N-dimethylacetamide. 1.09 g of pyromellitic dianhydride was added, and the resulting mixture was stirred at room temperature. A glass plate was coated with the polyamic acid solution thus obtained, and the solvent was removed at 50° C. under reduced pressure to give a polyamic acid film.
Comparative Example 1
Side chain-free polyamic acid/polysiloxane blend
0.115 g of the polyamic acid obtained in Reference Example 9 and 0.268 g of polydimethylsiloxane with an average degree of polymerization of 600 were dissolved in a mixed solvent (7:3) of tetrahydrofuran and N,N-dimethylacetamide, and a glass plate was coated with the clear solution thus obtained. The polyamic acid and polydimethylsiloxane separated when the solvent was removed under reduced pressure.
Reference Example 10
Synthesis of 2-(3-butenyloxy) terephthalic acid
6.62 g of 1,8-diazabicyclo[5.4.0]undecene and 100 mL benzene were added to 3.76 g hydroxyterephthalic acid (synthesized from bromoterephthalic acid by a known method) and the mixture was heated. 6.76 g of bromoethane dissolved in 38 mL benzene was added dropwise in and the reaction mixture was heated under reflux for 19 hours. The salt product was filtered off, and purification by column chromatography then yielded 4.66 g diethyl hydroxyterephthalate.
3.55 g of this diethyl hydroxyterephthalate was dissolved in 100 mL dimethylformamide and combined with 640 mg of crushed sodium hydroxide. 4.03 g of 4-bromo-1-butene dissolved in 20 mL of dimethylformamide was added dropwise in while cooling on an ice bath. After stirring the reaction for 16 hours, purification by the usual methods gave 1.74 g of diethyl 2-(3-butenyloxy)terephthalate.
1.74 g of this diethyl 2-(3-butenyloxy) terephthalate was dissolved in 12 mL of ethanol, and this solution was added dropwise into an ethanol (17 mL) solution of 1.95 g of crushed potassium hydroxide on an ice bath. The precipitated white solid was recovered and dissolved in water. Neutralization with dilute hydrochloric acid gave 1.15 g of 2-(3-butenyloxy)terephthalic acid.
Reference Example 11
Synthesis of polysiloxane carrying terminal terephthaloyl chloride
1.00 g of 2-(3-butenyloxy) terephthalic acid synthesized according to Reference Example 10, 10 mg of ammonium sulfate, and 7.65 g of hexamethyldisilazane were combined and stirred at 60° C. for 24 hours. The ammonium sulfate was then removed and the excess hexamethyldisilazane was distilled off under reduced pressure to give 1.58 g of bistrimethylsilyl 2-(3-butenyloxy)terephthalate.
1.58 g of this bistrimethylsilyl 2-(3-butenyloxy)terephthalate product was dissolved in 29 mL of dry toluene and 70 microliters of a 3% chloroplatinic acid 2-propanol solution was added. This was followed by the dropwise addition of a toluene solution of 8.12 g of hydrogen-terminated polysiloxane as described in Reference Example 2 with an average value of 26.9 for n. After stirring at 60° C. for 4 hours, the silyl groups were eliminated by hydrolysis to yield 5.90 g of polysiloxane carrying terminal terephthalic acid.
2.70 g of this terephthalic acid-terminated polysiloxane product was stirred at 60° C. for 24 hours with 10 mg of ammonium sulfate and 7.65 g of hexamethyldisilazane. The product was polysiloxane carrying terminal bistrimethylsilyl terephthalate.
This product was stirred with 1.96 g of thionyl chloride at 80° C. for 3 hours. The excess thionyl chloride, etc., was removed under reduced pressure to give 2.70 g of polysiloxane carrying terminal terephthaloyl chloride.
Reference Example 12
Synthesis of 3,3'-bis(trimethylsiloxy)-4,4'-bis(trimethysiylamino)biphenyl
0.540 g of 3,3'-dihydroxy-4,4'-diaminobiphenyl (synthesized from 3,3'-dimethoxy-4,4'-diaminobiphenyl using hydrogen iodide by the known method) and 1.52 g of triethylamine were dissolved in 16 mL of dry tetrahydrofuran. 1.63 g of trimethylchlorosilane was then added dropwise followed by heating under reflux for 72 hours. Operating in an argon atmosphere, the salt was filtered off and the solvent, etc., was removed under reduced pressure to yield 3,3'-bis(trimethylsiloxy)-4,4'-bis(trimethylsilylamino)biphenyl.
Reference Example 13
Synthesis 1 of polysiloxane-grafted silylated polyhydroxyamide
Operating in an argon atmosphere, 0.347 g of the 3,3'-bis(trimethylsiloxy)-4,4'-bis(trimethylsilylamino)biphenyl synthesized in Reference Example 12 was dissolved in 10 mL of dry tetrahydrofuran. A solution prepared by dissolving 1.64 g of the terephthaloyl chloride-terminated polysiloxane synthesized in Reference Example 11 (average value of n=26.9) in 6 mL of dry tetrahydrofuran was then added dropwise over 30 minutes on a -20° C. to -15° C. bath. After stirring for 4 hours at the same temperature, stirring was continued at room temperature to give the polysiloxane-grafted silylated polyhydroxyamide.
Examples 15 through 17
Blends 1 of polysiloxane-grafted polybenzobisoxazole with polysiloxane
The polysiloxane-grafted silylated polyhydroxyamide synthesized in Reference Example 13 and polydimethylsiloxane with an average degree of polymerization of 600 were dissolved in tetrahydrofuran, and a glass plate was coated with the clear solution thus obtained. The solvent was then removed at 30° C. under reduced pressure to give a blend of the polysiloxane-grafted silylated polyhydroxyamide and the polydimethylsiloxane. This blend was subsequently heated for 19 hours at 300° C. in an argon atmosphere to give a blend of polysiloxane-grafted polybenzobisoxazole and polydimethylsiloxane. The production of the polybenzobisoxazole was confirmed in each case by the disappearance of absorptions attributable to NH (at 3300, 1645 and 1512 cm -1 ) in the IR spectrum. The results are reported in Table 2.
TABLE 2______________________________________ content of content of grafted polybenzobisoxazoleexample polybenzobisoxazole main chain compati-number (weight %) (weight %) bility______________________________________15 15.7 2.0 good16 31.0 4.0 good17 46.0 6.0 good______________________________________
Reference Example 14
Synthesis of polysiloxane-grafted polyhydroxyamide
A reaction solution as produced in Reference Example 13 was poured into a large quantity of methanol, and the precipitated polysiloxane-grafted polyhydroxyamide was recovered by filtration and drying.
Example 18
Blend 2 of polysiloxane-grafted polybenzobisoxazole with polysiloxane
A blend (content of polybenzobisoxazole main chain: 4.0 weight %) of polysiloxane-grafted polybenzobisoxazole and polydimethylsiloxane was prepared by the procedure of Example 15 through 17 using the polysiloxane-grafted polyhydroxyamide obtained in Reference Example 14 and polydimethylsiloxane with an average degree of polymerization of 600. The compatibility of this blend was good.
Reference Example 15
Synthesis of side chain-free silylated polyhydroxyamide
Operating in an argon atmosphere, 0.722 g of the 3,3'-bis(trimethylsiloxy)-4,4'-bis(trimethylsilylamino)biphenyl synthesized in Reference Example 12 was dissolved in 5 mL of dry N,N-dimethylacetamide, and the resulting solution was solidified on a dry ice/ethanol bath. The solution prepared by dissolving 0.290 g of terephthaloyl chloride in 2 mL of N,N-dimethylacetamide was then added. While stirring was continued, the bath was gradually warmed from 0° C. to room temperature, thus synthesizing the silylated polyhydroxyamide.
Comparative Example 2
Blend of side chain-free silylated polyhydroxyamide and polysiloxane
0.135 g of the silylated polyhydroxyamide synthesized in Reference Example 15 and 0.315 g of polydimethylsiloxane with an average degree of polymerization of 600 were dissolved in a mixed solvent (1:1) of tetrahydrofuran and N,N-dimethylacetamide, and a glass plate was coated with the clear solution thus obtained. The polyhydroxyamide and polydimethylsiloxane separated when the solvent was removed under reduced pressure.
Reference Example 16
Synthesis of 2-(3-butenyloxy) terephthaloyl chloride
0.100 g of the 2-(3-butenyloxy) terephthalic acid synthesized in Reference Example 10 was dissolved in 5 mL of benzene. 0.757 g of thionyl chloride was added, and this mixture was stirred for 3.5 hours at 80° C. The excess thionyl chloride and the solvent were removed under reduced pressure to give 2-(3-butenyloxy)terephthaloyl chloride quantitatively.
Reference Example 17
Synthesis 2 of polysiloxane-grafted silylated polyhydroxyamide
Using 0.620 g of the 3,3'-bis(trimethylsiloxy)-4,4'-bis(trimethylsilylamino)biphenyl synthesized in Reference Example 12, 2.70 g of the terephthaloyl chloride-terminated polysiloxane (average value of n =26.9) synthesized in Reference Example 11, and 33.6 mg of the 2-(3-butenyloxy)terephthaloyl chloride synthesized in Reference Example 16, a silylated polyhydroxyamide was synthesized by the procedure of Reference Example 13. This silylated polyhydroxyamide had a polysiloxane-grafted monomer unit/3-butenyloxy-substituted monomer unit molar ratio of 9:1.
Example 19
Polybenzobisoxazole/silicone rubber molecular composite 1
2.00 g of polydimethylsiloxane carrying the vinyl group at both terminals (vinyl group content: 0.12 weight %) and 50.0 mg of the silylated polyhydroxyamide synthesized in Reference Example 17 (polysiloxane-grafted monomer unit/3-butenyloxy-substituted monomer unit molar ratio =9:1) were dissolved in tetrahydrofuran. 10 microliters of a 0.034% tetrahydrofuran solution of a platinum-divinyltetramethyldisiloxane complex, 10 microliters of a 0.15% tetrahydrofuran solution of 2-methyl-3-butyn-2-ol, and 22 mg of crosslinker with the formula ##STR18## were added to this solution, and the resulting mixture was poured into a stainless steel casting mold. The polysiloxane was then cured while removing the solvent by heating the mixture for 1 hour at 60° C., 2 hours at 80° C., and 19 hours at 100° C., which gave a silicone rubber film that contained silylated polyhydroxyamide. This film was heated for 19 hours at 300° C. in an argon atmosphere, thus producing a film of a silicone rubber molecular composite that contained 0.3 weight % polybenzobisoxazole main chain. When this film was subjected to tensile testing, the tensile strength was 2.3 kg/cm 2 and the elongation at break was 320%.
Example 20
Polybenzobisoxazole/silicone rubber molecular composite 2
A terephthaloyl chloride-terminated polysiloxane with an average value for n of 6.9 was synthesized by the procedure of Reference Example 11. Using this polysiloxane, a silylated polyhydroxyamide was synthesized by the procedure of Reference Example 17. This silylated polyhydroxyamide had a polysiloxane-grafted monomer unit/3-butenyloxy-substituted monomer unit molar ratio of 9:1, and the average value of n for its side chains was 6.9. The procedure of Example 19 was used to prepare a film of a silicone rubber molecular composite that contained 0.3 weight % polybenzobisoxazole main chain. When this film was subjected to tensile testing, the tebsuke strength was 5.7 kg/cm 2 and the elongation at break was 450%.
Comparative Example 3
Unfilled silicone rubber
An unfilled silicone rubber was produced by the procedure of Example 19 using the same vinyl-endblocked polydimethylsiloxane, platinum-divinyltetramethyldisiloxane complex, 2-methyl-3-butyn-2-ol, and crosslinker as in Example 19. The rubber film produced by heating this unfilled silicone rubber for 19 hours at 300° C. in the same manner as in Example 19 was also subjected to tensile testing: the tensile strengths was 1.5 kg/cm 2 and the elongation at break was 320%. | Methods are disclosed for the blending of inherently incompatible polymer systems to provide compositions comprising (i) 1 to 99.99 percent by weight of a diorganopolysiloxane; and (ii) 0.01 to 99 percent by weight of an organopolysiloxane-grafted rigid linear aromatic polymer selected from the group consisting of organopolysiloxane-grafted polyimide and organopolysiloxane-grafted polybenzobisoxazole. | 2 |
This application claims the benefit of priority under 35 U.S.C. §119(e) of U.S. Provisional Patent Application No. 60/818,609 filed on Jul. 5, 2006.
This invention relates to an aqueous sodium borohydride mixture having increased stability, especially at high temperatures.
Aqueous borohydride solutions having relatively good stability are known. For example, solutions containing about 12% sodium borohydride and about 40% sodium hydroxide are sold commercially. In some applications, a stable borohydride-containing solution having less sodium hydroxide is desired, e.g., in hydrogen fuel cells. Such a solution is described in U.S. Pat. No. 6,866,689; it contains about 44% sodium borohydride and about 0.2% sodium hydroxide. However, this solution exhibits relatively high rates of borohydride decomposition at elevated temperatures.
The problem addressed by this invention is to find an aqueous formulation of borohydride that has improved stability at elevated temperatures.
STATEMENT OF INVENTION
The present invention provides an aqueous mixture comprising: (a) from 15% to 65% of at least one borohydride compound; (b) from 1% to 10% of at least one metal hydroxide; and (c) from 0.1% to 20% of at least one absorbent polymer or excipient. The invention is further directed to a method for stabilizing aqueous borohydride mixtures by adding at least one absorbent polymer or excipient.
DETAILED DESCRIPTION
Percentages are weight percentages and temperatures are in ° C., unless specified otherwise. A “borohydride compound” is a compound containing the borohydride anion, BH 4 − . An “absorbent polymer” is a polymer capable of absorbing water. Preferably, absorbent polymers are chosen from among water-soluble polymers (polymers having water solubility of at least 1%, alternatively at least 5%), cellulose and its derivatives, and cross-linked polymers. Cross-linked polymers preferably have carboxyl, amide, hydroxy, amino, or ether groups, or a combination thereof, to facilitate dispersion in water. “Excipients” are pharmaceutical excipients as defined, e.g., in Handbook of Pharmaceutical Excipients , A. Wade & P. J. Weller (1964). Especially preferred excipients are those used as tablet disintegrants, e.g., polyacrylic acids, angelic acid, calcium alginate, carboxymethylcellulose (e.g., calcium or sodium salt), chitosan, croscarmellose sodium, crospovidone, docusate sodium, guar gum, polacrilin potassium, povidone, sodium alginate, sodium starch glycolate, and starch. In one embodiment of the invention, excipients have a water solubility of at least 0.5%, alternatively at least 1%. In one embodiment of the invention, preferred absorbent polymers include polyacrylic acids, polyacrylamide co polyacrylic acid, copolymers of acrylic acid (e.g., polyacrylic acid co polyethylene oxide), polyvinylpyrrolidone, polyvinylpyridine, polyvinylpyridine N-oxide, polyvinylimidazole, ethoxylated polyethylenimine, cellulose esters (e.g., acetate, butyrate), hydroxyalkyl celluloses, and carboxymethyl cellulose. The aqueous mixture of the present invention may be a solution, slurry, gel, or any other fluid mixture at temperatures of at least 40° C.: Mixtures having higher concentrations of borohydride, e.g., at least 50%, typically are solids or thick slurries at ambient temperature of about 25° C., but become fluid at higher temperatures.
In one embodiment, the amount of borohydride compound(s) is at least 20%, alternatively at least 25%. In one embodiment, the amount of metal hydroxide(s) is no more than 8%, alternatively no more than 6%, alternatively no more than 4%. In one embodiment of the invention, the amount of metal hydroxide is at least 2%, alternatively at least 3%. In one embodiment, the amount of borohydride compound is no more than 55%, alternatively no more than 50%, alternatively no more than 45%, alternatively no more than 40%. Preferably, the borohydride compound is a metal salt which has a metal cation from groups 1, 2, 4, 5, 7, 11, 12 or 13 of the periodic table, or a mixture thereof. In one embodiment, the borohydride compound is an alkali metal borohydride or combination thereof, alternatively it comprises sodium borohydride (SBH) or potassium borohydride or a mixture thereof, alternatively sodium borohydride. Preferably, the metal hydroxide is an alkali metal hydroxide or combination thereof; alternatively sodium, lithium or potassium hydroxide, or a mixture thereof; alternatively sodium hydroxide or potassium hydroxide; alternatively sodium hydroxide. More than one alkali metal borohydride and more than one metal hydroxide may be present.
In one embodiment of the invention, the amount of absorbent polymer(s) and/or excipient(s) is at least 0.2%, alternatively at least 0.4%, alternatively at least 1%, alternatively at least 2%. In one embodiment of the invention, the amount of absorbent polymer(s) and/or excipient(s) is no more than 15%, alternatively no more than 12%, alternatively no more than 10%, alternatively no more than 8%. In one embodiment of the invention, extremely small amounts of absorbent polymer(s) and/or excipient(s) are required; at least 0.1%, but no more than 1%, alternatively no more than 0.5%. For example, partially neutralized polyacrylic acids, or copolymers containing at least 20% acrylic acid monomer units, alternatively at least 30%, alternatively at least 50%, alternatively at least 75%, may require only very small amounts of absorbent polymer(s) and/or excipient(s). The degree of neutralization of the polyacrylic acids added to the borohydride compound(s) is not critical because the aqueous mixture contains additional base, so that the acids typically will be completely neutralized in the aqueous mixture. For polymers used in this invention, a weight average molecular weight of at least 1500 is preferred, alternatively at least 3000, alternatively at least 5000.
In one embodiment of the invention, the aqueous mixture is substantially free of substances that catalyze hydrolysis of borohydride, e.g., salts of transition metals such as Co, Ru, Ni, Fe, Rh, Pd, Os, Ir, Pt, or mixtures thereof, and borides of Co and/or Ni.
The aqueous mixture of this invention also may be used in the fields of synthesis and metal recovery.
EXAMPLES
TABLE 1 Decomposition rate of solutions containing 25% SBH, 3% NaOH with additives at room temperature and 60° C. Rate of Rate of decomposition decomposition % decrease 25% SBH, 3% NaOH Wt % of At RT, at 60° C. in decomposition with Additive additive % SBH/day % SBH/day rate at 60° C. None, 25% NaBH 4 , N/A −0.12 −0.958 N/A 3% NaOH Poly acrylic acid 0.5 −0.05 −0.564 41 partial sodium salt, lightly cross linked (solid) CAS # 76774- 25-9 Poly acrylamide co 0.5 −0.074 −0.662 31 acrylic acid partial sodium salt (solid) M w = 15,000,000 Poly acrylic acid co 0.5 −0.012 −0.614 36 poly ethylene oxide (solid) CAS # 27599- 59-56-0 Poly vinyl 0.5 −0.004 −0.734 23 pyrrolidone (solid) M w = 10,000; CAS # 9003-39-0 Carboxy methyl 0.5 −0.032 −0.728 24 cellulose sodium salt (solid) M w = 70,000; CAS # 9004-39-4
The addition of poly acrylic acid partial cross linked partial sodium salt to higher-concentration sodium borohydride formulations also results in decreasing the hydrolysis rates of the 40 and 50 wt % formulations. An unexpected phenomenon has been observed when these formulations are heated for long periods of time. After an initial induction period, the rate of hydrolysis of the borohydride decreases to nearly zero.
TABLE 2
Decomposition rate (“DR”) of solutions containing 40% SBH,
5% NaOH with additives at room temperature and 50° C.
DR at 50° C.
DR at
%
% SBH/Day
40% SBH, 5%
Wt %
DR at
50° C.
decrease
After
NaOH with
of
RT %
% SBH/
in DR
induction
Additive
additive
SBH/day
Day
at 50° C.
period
None, 40%
N/A
0.0549
0.3604
N/A
N/A
NaBH 4 , 5%
NaOH
Poly acrylic
0.5
0.0333
0.1139
68
0.0547
acid partial
sodium salt,
lightly cross
linked (solid)
CAS # 76774-
25-9
Poly acrylic
4%
0.0339
0.1716
52
0.0084
acid partial
sodium salt
(Liquid) M w =
30,000; CAS #
9003-04-07
TABLE 3
Decomposition rate of solutions containing 50% SBH,
5% NaOH with additives at room temperature and 58° C.
DR at 58° C.
DR at
% SBH/day
50% SBH, 5%
Wt %
DR at
58° C.
%
after
NaOH with
of
RT %
% SBH/
decrease
induction
Additive
additive
SBH/day
day
in DR
period
None, 50%
N/A
0.0031
0.35
N/A
N/A
NaBH 4 , 5%
NaOH
Poly acrylic
0.5%
—
0.03121
91
0.01165
acid partial
sodium salt,
lightly cross
linked (solid)
CAS #
76774-25-9
Poly acrylic
4%
—
0.01715
95
0.01388
acid partial
sodium salt
(Liquid)
M w = 30,000;
CAS #
9003-04-07
TABLE 4
Decomposition rate of solutions containing 25% SBH, 5% NaOH with
different wt % of poly acrylic acid), partial sodium salt solid at 22° C.
Wt %
Rate of decomposition %
Temp ° C.
additive
SBH/Day
% Difference
22
0
0.026
N/A
22
0.5
0.011
57.7
22
1
0.0485
22
1.5
0.0473
22
2
0.0473
22
4
0.025
3.8
TABLE 5
Decomposition rate of solutions containing 25% SBH, 5% NaOH with
different wt % of poly acrylic acid), partial sodium salt solid at 60° C.
Wt %
Rate of decomposition %
Temp ° C.
additive
SBH/Day
% Difference
60
0
0.4334
N/A
60
0.5
0.3764
13.2
60
1
0.409
5.6
60
1.5
0.424
2.1
60
2
0.4114
5.1
60
4
0.4201
3.1
TABLE 6
Decomposition rate of solutions containing 25% SBH, 5% NaOH with
different wt % of poly (acrylic acid sodium salt 30% in water
M w = 15,000 at 22° C. (wt. % additive in this table,
and following tables based on total polymer/water formulation)
Rate of
Rate of decomposition
Wt %
decomposition,
of standard, %
%
Temp ° C.
additive
% SBH/Day
SBH/Day
Difference
22
0
22
10
0.1161
0.0114
22
5
0.0019
0.1029
98.1
22
1
0.046
0.0421
TABLE 7
Decomposition rate of solutions containing 25% SBH, 5% NaOH with
different wt % of polyacrylic acid sodium salt 30% in
water M w = 15,000 at 60° C.
Rate of
Rate of
decomposition of
Wt %
decomposition,
standard, %
Temp ° C.
additive
% SBH/Day
% SBH/Day
% Difference
60
0
60
10
0.3982
0.4993
20.2
60
5
0.4301
0.4964
13.3
60
1
0.4236
0.4399
3.7
TABLE 8
Decomposition rate of solutions containing 25% SBH, 5% NaOH with
15 wt % of polyethyleneimine 80% ethoxylated at 22° C.
Rate of
Wt %
decomposition %
%
Temp ° C.
additive
SBH/Day
Difference
Standard
0
0.0585
N/A
22
Polyethylenimine
15
0.0116
80.1
80%, ethoxylated
37% in water
M w = 50,000; CAS
# 26558-46-8
22
Polyethylenimine
15
0.0321
45.1
80% ethoxylated
15
35 to 40% in
water M w =
70,000; CAS #
26558-46-8
TABLE 9
Decomposition rate of solutions containing 25% SBH, 5% NaOH with
15 wt % of polyethyleneimine 80% ethoxylated at 60° C.
Rate of
Temp
Wt %
decomposition
%
° C.
additive
% SBH/Day
Difference
Standard
0
0.5782
N/A
60
Polyethyleneimine 80%
15
0.5096
11.8
ethoxylated, 37% in water
M w = 50,000; CAS #
26558-46-8
60
Polyethylenimine 80%
15
0.5052
12.6
ethoxylated, 35 to 40% in
water M w = 70,000; CAS #
26558-46-8
TABLE 10
Decomposition rate of solutions containing 25% SBH, 5% NaOH with
15 wt % different MW polyacrylic acid sodium salts at 22° C.
DR
Temp
Wt %
% SBH/
%
° C.
additive
Day
Difference
Standard
0
0.0585
N/A
22
Poly (acrylic acid sodium salt 45%
15
0.06493
Higher
in water M w = 1,200; CAS # 9003-
by 10
04-7
22
Poly (acrylic acid sodium salt 45%
15
0.0257
56.0
in water M w = 8,000; CAS # 9003-
04-7
22
Poly (acrylic acid sodium salt 40%
15
0.0091
84.4
in water M w = 30,000; CAS #
9003-04-7
TABLE 11
Decomposition rate of solutions containing 25% SBH, 5% NaOH with
15 wt % of different MW poly acrylic acid sodium salts at 60° C.
DR
Temp
Wt %
%SBH/
%
° C.
additive
Day
Difference
Standard
0
0.5782
N/A
60
Poly (acrylic acid sodium salt 45%
15
0.3812
34.0
in water M w = 1,200; CAS #
9003-04-7
60
Poly (acrylic acid sodium salt 45%
15
0.3607
37.6
in water M w = 8,000; CAS #
9003-04-7
60
Poly (acrylic acid sodium salt 40%
15
0.3736
35.38
in water M w = 30,000; CAS #
9003-04-7 | A stabilized aqueous mixture containing at least one borohydride compound and at least one metal hydroxide compound. The mixture has improved stability with regard to decomposition of borohydride, especially at elevated temperatures. | 2 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a shock wave sterilizer for sterilizing fluid or liquid food including various juices, cooling beverage, milk, yogurt, and so forth.
2. Description of Related Art
A thermal sterilization method and a high pressure sterilization method are known as means for sterilizing these kinds of food. In the thermal sterilization method, food is heated at a predetermined temperature through a thermal conduct so that the food can be sterilized. In the high pressure sterilization method, food is subjected to a high pressure, typically hundreds to thousands times atmospheric pressure to be sterilized.
However, the thermal sterilization method, results in degeneration of protein in food because of heating. In addition, thermally sterilized food sometimes emits a smell unique to thermal sterilization. On the other hand, a conventional apparatus for the high pressure sterilization method is large, and its sterilizing ability is poor since the apparatus is incapable of performing successive sterilization.
SUMMARY OF THE INVENTION
The present invention has been made to solve such problems. A principal object of the present invention is to provide an inexpensive shock wave sterilizer which efficiently sterilizes food by using a shock wave.
A shock wave sterilizer in accordance with the present invention is characterized in comprising an elastic container for containing food, a shock wave source which is disposed to face the elastic container and a pressure transfer medium which is interposed between the shock wave source and the elastic container.
A shock wave emitted from the shock wave source is transferred to the elastic container through the pressure transfer medium, thereby the shock wave is first applied onto food contained in the container and an expansion wave is next applied onto the food with little time delay. When the shock wave and the expansion wave are applied, differences in the shock impedance of materials constituting a cell of bacteria create differences in the pressure change within the cell. This in turn creates non-equilibrium force in the cell, and as a result, the cell is destroyed and the food is sterilized. The time required for radiating the shock wave is only a few hundred micro-seconds so that there will be no chemical change due to a high temperature or a change in the pressure such as thermal degeneration of protein or the like. Therefore, food can be sterilized at a normal temperature. Further, reliable sterilization is possible without any large scale complex apparatus.
In addition, by supplying food into the elastic container through a supply pipe and discharging processed food through a discharge pipe, food can be sterilized successively.
Still further, batch sterilization is realized when the elastic container is constructed so as to seal contained food inside.
The above and further objects and features of the invention will more fully be apparent from the following detailed description with accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic vertical cross sectional view showing a structure of a shock wave sterilizer according to a first embodiment of the present invention;
FIG. 2 is an enlarged cross sectional view of FIG. 1 taken along the line II--II;
FIG. 3 is an enlarged cross sectional view showing a structure of a shock wave sterilizer according to a second embodiment of the present invention;
FIG. 4 is an enlarged cross sectional view showing a structure of a shock wave sterilizer according to a third embodiment of the present invention; and
FIG. 5 is a schematic vertical cross sectional view showing a structure of a shock wave sterilizer according to a fourth embodiment of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
In the following, the present invention will be described in relation to preferred embodiments thereof while referring to the associated drawings.
Embodiment 1
FIG. 1 is a schematic vertical cross sectional view showing a structure of a shock wave sterilizer according to the first embodiment of the present invention, and FIG. 2 is an enlarged cross sectional view of FIG. 1 taken along the line II--II. In the drawings, numeral 1 denotes a container having the shape of a hollow rectangular box or a cylinder and made of shock resistant plastic or the like. The container 1 contains a holder 2, a pair of electrodes 3a and 3b, terminals 4a and 4b attached to the electrodes 3a and 3b respectively and disposed in alignment with each other, and a thin copper wire 5 stretched between the terminals 4a and 4b. Also contained in the container 1 is a pressure medium, e.g., water 6 filled to a certain depth so that the holder 2, the bottom section of the electrodes 3a and 3b, the terminals 4a and 4b and the thin copper wire 5 are immersed in the water 6. Alternatively, other types of liquid not harmful to human beings can be used instead of the water 6.
The holder 2 made of metal or synthetic resin is approximately rectangular. On the top surface of the holder 2, an approximately arcuate groove 2a is formed as shown in FIG. 2. On the circumferential wall of this groove 2a, a plurality of narrow grooves 2b each shaped approximately as an arc in cross section are formed approximately at equal intervals so as to be approximately parallel to an axis of the groove 2a. An elastic tube 7 is inserted with part of circumferential wall thereof inlaid in each arc groove 2b of the groove 2a.
The elastic tube 7 made of rubber or synthetic resin 7 is linked at its one end to a pipe 9 that supplies the material, such as food, to be sterilized which is disposed near one end portion of the holder 2, and is linked at its other end to a food discharge pipe 10. The food supply pipe 9 includes a check valve and a pump and penetrates the container 1 so as to be linked at its other end to an unprocessed food tank for containing unprocessed fluid food. The food discharge pipe 10 is also provided with a check valve and, penetrates the container 1 so as to be linked at its other end to a processed food tank for containing processed fluid food. Fluid food introduced into the elastic tubes 7 in the container 1 through the food supply pipe 9 from the unprocessed food tank is sterilized within the elastic tubes 7. Processed fluid food is ejected from the elastic tubes 7 into the processed food tank through the food discharge pipe 10.
The electrodes 3a and 3b are made of conductive material such as copper, and connected to a direct current source via lead wires A and B. A capacitor 8 is connected between the lead wires A and B. A switch C is installed on the lower end of either the lead wire A or B. In the vicinity of bottom ends of the electrodes 3a and 3b, the terminals 4a and 4b are disposed which are also made of conductive material and equipped with a chuck function. The thin copper wire 5 is stretched between the terminals 4a and 4b to fit with the center of curvature of the groove 2a. When the capacitor 8 intermittently discharges due to intermittent ON/OFF operations of the switch C, a current of about 80 kJ flows through the thin copper wire 5. When a current flows through the thin copper wire 5, the thin copper wire 5 is heated due to Joule heat, and is finally vaporized because of overheating. Because of the expansion in the volume of the thin copper wire 5 during vaporization, shock waves 11 are created. This takes about 30 microseconds from the start of application of the current. After the thin copper wire 5 was vaporized, a plasma is generated, through which an electric potential is created between the terminals 4a and 4b.
The shock waves 11 are transmitted into the groove 2a of the holder 2 and thence into the respective elastic tubes 7 in the groove 2a with the water 6 as a transfer medium as shown in FIG. 2. Hence, the shock waves are first applied onto fluid food which is contained in the elastic tubes 7 and the expansion waves are next applied onto the food with a little time delay. When the shock waves and the expansion waves are applied, differences in the shock impedance of materials constituting a cell of a bacteria create differences in pressure change within the cell. This in turn creates non-equilibrium force in the cell, and as a result, the cell is destroyed and the food is sterilized. The time required for radiating the shock waves is only a few hundred microseconds so that there will be no chemical change due to a high temperature or a change in the pressure. In the first embodiment, sterilization is performed while supplying fluid food into the elastic tubes 7 through the food supply pipe 9 and discharging processed food through the food discharge pipe 10. Therefore, successive sterilization can be easily realized.
Upon completion of one wire explosion, a new thin copper wire 5 is forwarded from one of the terminals 4a or 4b toward the other and held by the other, and the wire explosion as described above is then performed again. Thus, while food is passed through the elastic tubes 7 at a predetermined speed from the Food supply pipe 9 side, the shock waves can be applied on the food once or for a plurality of times.
A pressure applied to the Fluid food was calculated based on the speed of the shock waves which was estimated from photographs intermittently taken at a high speed by an image converter camera. That is, wire explosion under water was shot with the image converter camera, and a speed u c at the shock front was calculated. According to the calculation, the speed u c was 100 m/s.
From this value, an upward pressure ΔP was calculated in accordance with the equation (1) below.
ΔP=ρ.sub.0 U.sub.s u.sub.c (1)
U.sub.s =ρ.sub.1 (U.sub.s -u.sub.c)/ρ.sub.0
P.sub.1 =(P.sub.0 +B)(ρ.sub.1 /ρ.sub.0).sup.n
where
U s : speed behind the shock wave
u c : speed of the shock wave
ρ 0 : density of the water
ρ 1 : density of the water behind the shock wave
P 0 : pressure of the water
P 1 : pressure of the water behind the shock wave
n: 7.415
B: 2.963×10 8 Pa
As a result, it was confirmed that the upward pressure ΔP was about at 3000 times atmospheric pressure. (Theoretically, the speeds of the shock waves drastically decrease due to the expansion waves.) However, the actual decrease was less drastic than the theoretical one. This is assumed to be because there still is a continued supply of energy due to discharging between the terminals 4a and 4b even after the thin copper wire 5 was vaporized.
EXAMPLE OF EXPERIMENT
A description will be given next on an actual result of sterilization of elastic tubes 7 containing microorganisms. Shock waves were generated by discharging electrical energy of 8 kJ at a thin wire which has a thickness of 0.2 mm. The holder 2 used was made of soft polyethylene which has a characteristic close to a shock impedance of the water 6. This is to protect the container against destruction due to interference among the shock waves. In this experiment, a peak pressure of 1000 times atmospheric pressure was created. A yeast used in the experiment was Saccha romyces cerevisiae of a size of about 5 to 10 micro-m. The length of Brine shrimps used was 0.5 mm. The yeast was introduced in the elastic tubes 7 so that the optical density was 0.3, and impact was applied on the yeast once in one test and five times in other test. Several tens of Brine shrimps were contained in each elastic tube 7 and subjected to impact for one time.
According to observation through a scanning electron microscope, 20% of the yeast died due to one application of impact. On the other hand, five applications of impact killed a proportionally larger percentage of the yeast. Hence, it is believed that destruction due to impact occurs in accordance with a probability. With respect to the destructed state, the destruction is not like a shear fracture of a cell wall like sonicator, but is rather like spalling.
According to observation through an optical microscope, most of the brine shrimps were fractured into small pieces after application of the impact.
From the above, it is understood that one to a few applications of impact realizes sterilization.
With respect to the arc grooves 2b, they can be winding grooves.
Embodiment 2
FIG. 3 is an enlarged cross sectional view showing a structure of a shock wave sterilizer according to the second embodiment of the present invention. FIG. 3 corresponds to FIG. 2. Although the first embodiment requires that a plurality of the elastic tubes are disposed in the grooves 2a of the holder 2, in the second embodiment, a plurality of thin copper wires 5 are disposed around one elastic tube 7 so as to be parallel to each other. The structure of the second embodiment is otherwise the same as that of the first embodiment.
The plurality of the thin copper wires 5 are exploded at the same time to radially apply shock waves upon the elastic tube 7. As a result, fluid food is sterilized.
Embodiment 3
FIG. 4 is an enlarged cross sectional view showing a structure of a shock wave sterilizer according to the third embodiment of the present invention. FIG. 4 corresponds to FIG. 2. Although the first embodiment requires that the elastic tubes 7 are disposed in the groove 2a of the holder 2, in the third embodiment, the holder 2 is replaced with a cylindrical holder 12 which has a predetermined thickness. In the inner circumferential surface of the holder 12, a plurality of arc grooves 2b are formed to inlay elastic tubes 7. A thin copper wire 5 is disposed along a central line of the holder 12. The structure of the third embodiment is otherwise the same as that of the first embodiment.
By exploding the thin copper wire 5, shock waves are applied on the elastic tubes 7 which are disposed around the thin copper wire 5. As a result, fluid food is sterilized.
Embodiment 4
FIG. 5 is a schematic vertical cross sectional view showing a structure of a shock wave sterilizer according to the fourth embodiment of the present invention. FIG. 5 corresponds to FIG. 1. In the fourth embodiment, the elastic tubes 7 are replaced with elastic containers 17 each sealed at the both ends. Hence, the food supply pipe 9 and the food discharge pipe 10 are omitted. As in the first embodiment, the elastic containers 17 are inserted in the arc grooves 2b of the groove 2a which is formed in the holder 2.
In the fourth embodiment, by changing the elastic containers 17 to other elastic containers 17, batch sterilization can be performed.
Although the foregoing embodiments use the thin copper wire 5 as a shock wave source, any other conventional source can be used instead of the thin copper wire 5.
As this invention may be embodied in several forths without departing from the spirit of essential characteristics thereof, the present embodiment is therefore illustrative and not restrictive, since the scope of the invention is defined by the appended claims rather thin by the description preceding them, and all changes that fall within metes and bounds of the claims, or equivalence of such metes and bounds thereof are therefore intended to be embraced by the claims. | A shock wave sterilizer for sterilizing a fluid medium, such as food, by having the fluid medium in an elastic container impacted by shock waves and expansion waves emitted from a shock wave source formed by a source of electric current discharging through an electrical conductor to vaporize the electrical conductor to produce a shock wave that is transmitted through a pressure transfer medium to the container and the fluid medium therein. | 0 |
CROSS-REFERENCE
This application claims priority of German Application No. 199 21 092.6-23 filed Apr. 30, 1999, a copy of which is Attachment A hereto, the disclosure of which is incorporated fully herein by reference.
FIELD OF THE INVENTION
The invention relates to a method for standardizing the pane position of an external force actuated vehicle window lifter.
BACKGROUND OF THE INVENTION
Standardizing the pane position is of particular importance in the case of vehicle window lifters which are fitted with a device for detecting a jammed object. With these window lifters the drive is automatically switched off and where necessary reversed when the window pane during its upward movement strikes an obstruction which would otherwise be clamped between the upper edge of the pane and the window frame.
However there is a problem here in that the movement of the window pane into the upper pane seal could be interpreted as a jamming case on account of the resistance exerted by the pane seal against the displacement movement of the window pane. The window lifter would then be automatically switched off and the window pane could not then be moved completely into the upper pane seal. To solve this problem various proposals have been put forward in order to deactivate the anti-jam protection as the window pane enters into the upper pane seal, see here DE 196 28 203 C1. However in order to be able to do this it is necessary to determine accurately the relevant position of the window pane during its displacement movement.
For these reasons it is customary prior to initially operating an external force actuated window lifter or even after its repair to move the window pane once into its closed position in order to standardize the pane position. This upper end position of the window pane then serves as a zero or reference position for the window pane, in relation to which all individual displaced positions of the window pane can be determined along its displacement path.
In view of the importance of standardizing the pane position for a satisfactory functioning of an anti-jam protection system and furthermore in general for a reliable detection of the actual position of a displaceable window pane it is absolutely crucial to eliminate faults as far as possible when standardizing the pane position. For faults in the standardizing of the pane position can lead for example to a jamming case which occurs as the window pane is raised being misinterpreted by the anti-jam protection system as the window pane moving into the upper pane seal. The result of this would be that the drive of the window lifter is not switched off but rather is operated further with an increased current supply so that the resistance of the supposed pane seal can be overcome. This can lead to serious injury particularly in the case where part of the body is jammed.
SUMMARY OF THE INVENTION
The object of the invention is to provide a method for standardizing the pane position of a window lifter wherein a faulty standardizing of the pane position is reliably eliminated as far as possible.
According to this in order to check whether the window pane during standardizing has properly reached its upper end position (closed position), the change is evaluated in a value correlated with the dynamics of the window pane as the window pane enters into the seal area associated with the closed position.
The invention is based on the knowledge that the dynamics of the window pane when entering into the pane seal associated with the closed position is influenced in a characteristic way. Therefore by taking into account the dynamics of the window pane it can be readily checked whether the window pane has actually properly entered into the upper sealing area. More particularly it can be reliably established whether during standardizing of the pane position the entrance of the window pane into the closed position is prevented through a faulty fitting of the window lifter or through an object jammed between the window pane and the seal area. In the latter case the end position reached during standardizing the pane position is recognised as a position not corresponding to the actual closed position and therefore is not used consequently as the reference or zero point position of the window pane.
The failed standardizing can be indicated through an optical or acoustic signal. Furthermore after a failed standardizing the automatic function of the external force actuated window lifter is not activated, that is for as long as no proper standardizing of the pane position has been completed the window lifter cannot be moved automatically into its upper end position.
In particular the period length or speed of the drive (or of a displacement element connected with the drive, such as for example a gear part of the window lifter or the window pane itself), the current collection of the drive or the change of speed (acceleration) or change of current collection, can all be considered as values correlated with the dynamics of the window pane which can be used to check whether the window pane has reached its end position in the upper seal area. Basically when carrying out the method according to the invention any value can be used which reflects the influence of the upper pane seal on the dynamics of the window pane.
The entrance of the window pane into the seal area can be detected in particular from a local extremum of the value correlated with the dynamics, preferably the speed or period length, in dependence on the displacement site of the window pane. Thus when the window pane enters into the seal area there is normally at first a drop in the speed or an increase in the period length of the drive. After the window pane has moved by its leading upper edge a little further into the seal area however and has thereby overcome the resistance of the sealing lip of the seal area pressing against the window pane, a certain increase in the speed or decrease in the period length of the drive occurs again. A local minimum or local maximum respectively is hereby formed in the path of the speed or of the period length of the drive over the displacement path of the window pane. This is typical for the upper edge of the window pane entering into the seal area and can thus be used as a typical criterion for reaching the closed position of the window pane. If however the window pane during standardizing strikes an obstruction by its leading edge then the speed is decreased or the period length increased substantially continuously. It does not result in forming an extremum. The entrance into the seal area can thereby be clearly differentiated from striking an obstruction of another kind.
When evaluating the value correlated with the dynamics of the window pane not only should the actual displacement position of the window pane be used, but also where applicable some pre-values of the value correlated with the dynamics of the window pane. This prevents the result of the evaluation from being falsified by environmental factors, wear etc.
In a preferred embodiment of the invention the standardizing of the pane position is interrupted when after a predeterminable time span no path of the value correlated with the dynamics of the window pane has been observed which is characteristic of the entrance of the window pane into the seal area. This then signifies that during standardizing of the window pane no proper displacement movement of the window pane is taking place and thus a reliable standardizing of the pane position cannot be carried out.
Furthermore standardizing the pane position is preferably then only carried out when the window pane has moved at least along a path length which is greater than the extension of the pane seal in the direction of movement of the window pane. For only in such a case is it ensured that the characteristic behaviour of the value correlated with the dynamics of the window pane which appears as the leading edge of the window pane enters into the seal area can actually be observed. Advantageously the minimum displacement path of the window pane is thereby selected slightly larger than the extension of the seal area in order to ensure that the window pane when entering the seal area has already reached its usual displacement speed (swung-in system state).
BRIEF DESCRIPTION OF THE DRAWINGS
Further advantages of the invention will now be explained in further detail with reference to the embodiments shown in the drawings in which:
FIG. 1 a shows a window pane moved into its upper end position (closed position) for standardizing the pane position;
FIG. 1 b shows a window pane which has moved against an obstruction during standardizing of the pane position;
FIG. 2 a shows the leading edge of a window pane as it enters into the upper seal area;
FIG. 2 b shows the period length of the displacement drive of the window lifter in dependence on the displacement site, more particularly in the area of the upper pane seal;
FIG. 3 a shows the leading edge of the window pane running up against an obstruction during the raising of the window pane for the purpose of standardizing the pane position;
FIG. 3 b shows the path of the period length of the drive of the window lifter in dependence on the displacement site, more particularly when moving against an obstruction.
DETAILED DESCRIPTION
FIG. 1 a shows a window pane 1 which is adjustable by an external force actuated window lifter and which to standardize the pane position has been moved by its leading edge into a seal area 4 in its upper end position (closed position).
FIG. 1 b shows the same window pane 1 which here during lifting for the purpose of standardizing the pane position has moved against an obstruction 10 which has thus been jammed between the leading edge of the window pane 1 and the upper seal area 4 .
Since the entrance of the window pane 1 into the upper seal area 4 for the purpose of standardizing the pane position serves to establish a reference position of the window pane, to which during further operation of the window lifter each displaced position of the window pane 1 is related, in the embodiment according to FIG. 1 b the result is a faulty standardizing of the pane position. For the control or electronics unit of the window lifter serving to displace the window pane 1 the position illustrated in FIG. 1 b would be erroneously interpreted as the closed position of the window pane 1 . With a window lifter provided with an anti-jam protection system this means that in the automatic operation of the window lifter during raising of the window pane 1 the anti-jam protection system would be deactivated too early to ensure the proper entrance of the window pane 1 into the upper seal area. There is then the danger that a part of the body could be clamped between the leading edge of the window pane and the seal area 4 , thus resulting in injuries which are exactly to be eliminated by an anti-jam protection system.
FIG. 2 a shows the leading edge 2 of a window pane 1 which is about to move along its displacement direction z into the upper seal area 4 fixed on the vehicle body 3 . The window pane is hereby located at a distance d+s from its closed position which corresponds to the extension d of the seal area 4 along the displacement direction z of the window pane including a distance s. This distance s corresponds to the smallest possible extension of an obstruction along the displacement path z which can still cause a jamming case, thus for example the thickness of the finger of a small child.
If this window pane 1 is moved up further along the displacement direction z then its leading edge 2 passes into the seal area 4 where the sealing lips 5 , 6 of the seal area 4 press on both sides against the side faces of the window pane 1 so that the displacement speed of the window pane is reduced until it finally reaches its upper end position (closed position), which is shown in dotted lines in FIG. 2 a and is marked by reference number 1 ′.
Measurements have now shown that when the leading edge 2 of the window pane 1 enters the seal area 4 the result is not a continuous drop in the speed of the window pane. Rather at first a characteristic drop in the displacement speed of the window pane 1 is observed, and thus also in the speed of the drive motor of the window lifter, when the leading edge 2 of the window pane reaches the sealing lips 5 , 6 . After the resistance of these sealing lips 5 , 6 has been overcome the speed of the window pane then increases once again for a short while until it is completely braked on reaching its closed position.
This characteristic behaviour of the window pane as it enters into the seal is shown in FIG. 2 b where the period length of the drive is shown over the displacement site of the window pane. The displacement site z of the window pane is thereby defined so that the variable z is greater the further away the leading edge 2 of the window pane 1 is from the upper end position (closed position) of the window pane 1 . It can be clearly seen that as the window pane enters into the seal area an extremum E (additionally marked in FIG. 2 b by an arrow) is formed in the path of the period length T of the drive over the displacement site z of the window pane. From this extremum it is possible to establish that the window pane 1 has actually entered into the seal area 4 . Alternatively however a characteristic rise of the period length T immediately prior to reaching the extremum could be used here.
Obviously instead of the period length T it is also possible to enter the speed over the displacement site z. In this case instead of a local maximum (as can be seen in FIG. 2 b ) a local minimum would be formed in the path of the speed over the displacement site z. It would correspondingly result in a characteristic drop in the speed prior to reaching the local minimum.
FIG. 3 a shows the case where the leading edge 2 of the window pane 1 runs up against an obstruction 11 prior to reaching the pane seal 4 fixed on the vehicle body 3 and more particularly the sealing lips 5 , 6 thereof. In this case the window pane 1 can thus not reach its closed position which is shown in dotted lines in FIG. 3 a and is marked by the reference numeral 1 ′.
FIG. 3 b , in which the period length T of the drive is entered over the displacement site z of the window pane shows that in this case the change in the period length T takes a quite different course from that during the proper entrance of the window pane into the upper seal area as shown in FIGS. 2 a and 2 b.
From FIG. 3 b it can be seen in particular that the movement of the leading edge 2 of the window pane 1 against the obstruction 11 leads to a continuous sharp rise in the period length T (in FIG. 3 b marked by an arrow). A local extremum of the period length T is not hereby formed, and also the type of rise of the period length T is quite different from that when the pane enters the upper seal area. By evaluating the period length T of the drive of the window pane it is thus possible to reliably establish whether the window pane during standardizing of its pane position has actually reached its closed position in the upper seal area or whether it has moved against an obstruction during standardizing. In the latter case standardizing is interrupted as unsuccessful. An automatic raising of the window pane (e.g. by means of a single activation of a corresponding control element of the window lifter) is then prevented through a suitable programming of the control electronics of the window lifter. Only when a successful standardizing of the pane position has been carried out does the automatic raising of the window pane through the control electronics become possible.
With regard to the significance of this monitoring of the standardizing of the pane position for the reliable functioning of an anti-jam protection system, reference is made to the comments on this in the introductory discussion on the patent claims in order to avoid repetition here. | The invention relates to a method for standardizing the pane position of an external force actuated vehicle window lifter wherein the window pane is moved by means of the drive of the window lifter into a closed position provided with a seal and this closed position is used to standardize the pane position. According to the invention, in order to check whether the window pane has reached its closed position, the change is evaluated in a value (T) correlated with the dynamics of the window pane as the window pane enters into the seal area associated with the closed position. | 1 |
BACKGROUND AND SUMMARY OF THE INVENTION
The invention is directed to the field of optical multiplexing and more specifically to linear arrays of integrated quantum well lasers for wavelength division multiplexing.
In the prior art there has been described wavelength division (frequency) multiplexing using several different methods for obtaining a number of differing but closely spaced optical wavelengths. An article by Aiki, Nakamura and Umeda, "A Frequency Multiplexing Light Source with Monolithically Integrated Distributed-Feedback Diode Lasers" IEEE Jr. of Quan. Elect., Vol. QE-13, No. 4, April 1977, P220-223, describes a light source consisting of a plurality of GaAs-AlGaAs distributed-feedback (DFB) diode lasers with different wavelengths having a separation of about 20 Å. One major disadvantage to this approach is that the difference in the gratings causes many of the lasers to emit at wavelengths other than at the peak of their gain curve. Therefore, the lasing threshold current changes from laser-to-laser. An article by Alferov et al, "Wavelength Multiplexing DH AlGaAs Injection Laser Source with a Graded Composition Along the Active Layer", Jr. of Quan. Elect., vol. QE-17, No. 8, August 1981, P1530-33, describes the use of DH AlGaAs wafers with graded composition along the active layer for creation of multiwavelength laser source for wavelength division multiplexing. An article by Tsang, "CW Multiwavelength Transverse Junction Stripe Lasers Grown by Molecular Beam Epitaxy Operating Predominantly in Single-Longitudinal Modes", Appl. Phys. Letters 36(6), Mar. 15, 1980, P441-3, describes a new transverse junction stripe laser structure with multiple active layers each emitting a different wavelength. This is not true WDM because all wavelengths will contain the same data.
In the present invention an integrated quantum well laser array for wavelength division multiplexing is described having many lasers per output channel all grown on the same substrate and wherein a controlled variation of the active layer thickness from one of the plurality of lasers to the next is used to provide lasers of different wavelengths.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a diagrammatic end view of an array of integrated buried heterostructure lasers whose active regions are formed by microlayers with different thicknesses.
FIG. 2 is an edge view of a portion of FIG. 1.
FIG. 3 represents a full wafer with multiple identical arrays.
DESCRIPTION
The invention disclosed is directed to a large array of lasers for wavelength division multiplexing (WDM) in which perhaps 20 lasers are all grown on the same substrate. In a WDM operation with many lasers per output channel, a large wavelength range must be covered, for example about 100 Å. Each of these lasers must lase at a wavelength slightly different from the preceding laser (say by 5 Å or more), and it is desired that each laser will lase at a wavelength near the peak of its gain curve.
In FIG. 1 an abbreviated end view of an array of three such lasers is shown. For this example a buried heterostructure type laser is described. For these lasers an n-type GaAs substrate 10 has grown thereover by MOCVD (metal-organic chemical vapor deposition), or MBE (molecular beam epitaxy) a number of layers. A first cladding layer 11 covers the substrate surface in the initial process, the cladding layer may be Al x Ga 1-x As where x0.3≲x≲0.4.
FIG. 2 shows in more detail these layers. The quantum well active region 12 comprising a series of alternating thin layers of Al x Ga 1-x As (narrow band-gap well layers) and Al y Ga 1-y As (x≠y) (wide band-gap barrier layers) followed by a final Al x Ga 1-x As layer are grown over the entire layer. In the active region the Al x Ga 1-x As well layers, x may be ≅0 for example, and the Al y Ga 1-y As barrier layers, y may be 0.3. A controlled variation in the layer thickness of quantum well active region 12, at various locations of the wafer is used to provide lasers with different wavelengths. Such a method of thickness variation at various points on the wafer may be accomplished by either using a vapor growth (MOCVD) or MBE. The variation in layer thickness may be accomplished for example, by etching a pattern in the substrate to change the growth rate at various points on the wafer, or shadow masking the wafer during growth. Another cladding layer 13 is then grown over the active layers, followed by a GaAs layer 14 to which electrical contact can be made. Thus the grown layers 11, 12, 13, and 14 all cover the area of the substrate 10. The structure so far described must now be divided into multiple isolated lasers. For the buried heterostructure laser embodiment shown in FIG. 1, the isolation is accomplished by etching.
Locations for the multiple lasers are determined. The unwanted layer material between the individual buried heterostructure lasers (that is, in FIG. 1, between lasers 1, 2 and 3) is etched out leaving the lasers standing like mesas, and then the etched regions are refilled by growing cladding material 20 to fill the voids and thereby to provide isolation between the individual quantum well lasers.
Many identical arrays can be formed on a single substrate by repeating the pattern that produces the thickness variation as shown in FIG. 3. FIG. 3 represents a full wafer with multiple identical patterned areas 30 where multiple identical laser arrays will be grown. This is similar to producing multiple identical chips in integrated circuit design. The patterned areas 30 may be etched into the wafer surface. The multiple lasers are formed in each etched region as shown in FIG. 1.
There has been described herein the patterning of the wafer to produce many lasers of differing wavelength in a single growth process. The composition of the layers each of the many quantum well lasers on the wafer is the same. In quantum well lasers, the lasing wavelength is determined in part by the thicknesses of the microlayers in the active region. By changing the thickness of the microlayers in a controlled, known manner, then an array of lasers can be fabricated in which the emission wavelength separation between lasers is derived by fabricating lasers at the points where the known thickness of the quantum well layers produces the proper wavelengths. This structure will be useful for wavelength division multiplexing. In FIG. 1 it may be seen that the active region of laser 1 is thicker than the active region of laser 2 which in turn is thicker than the active region of laser 3. One advantage is that each of the integrated lasers is operating at a wavelength near the peak of its gain curve so that a low threshold current results for each laser. This simplifies the design of the integrated electronic circuit which drives the individual multiple quantum well lasers in the wavelength division multiplexing laser means.
Although the specification has described the array basically in terms of an AlGaAs--GaAs device, it is not intended to be so limited and the structure may be other than GaAs, such as InP and In x G 1-x As y P 1-y . | An integrated quantum well laser structure which has a plurality of quantum well lasers for providing a plurality of light beams each having a different wavelength for use in wavelength division multiplexing. | 1 |
CROSS REFERENCE TO RELATED APPLICATION
This is a utility application based upon the following provisional application which is incorporated herewith by reference and for which priority is claimed: U.S. Ser. No. 60/957,307 filed Aug. 22, 2007.
GOVERNMENT INTERESTS
Activities relating to the development of the subject matter of this invention were funded at least in part by United States Government, Naval Air Warfare Center Contract No. N68335-06-C-0339, and thus may be subject to license rights and other rights in the United States.
BACKGROUND OF THE INVENTION
In a principal aspect, the present invention relates to a high-performance carburized gear steel that can improve the performance of rotorcraft power transmissions, due to a unique and useful combination of surface hardness and core toughness. The U.S. Navy estimates that a 20% increase in gear durability would provide an annual cost saving of $17 million to the Defense Logistics Agency. However, the rotorcraft industry has not adopted a new gear steel for over twenty years, and instead focused on surface processing optimizations such as laser-peening, super-finishing, and directional forging. Such processes are providing diminishing returns in durability improvements. The subject invention provides a solution complementary to process enhancements and enables high-performance gears having reduced size and weight which are capable of transmitting more power at increased operating temperatures.
Carburized X53 (U.S. Pat. No. 4,157,258) is the incumbent material in rotorcraft transmissions. Compared to X53, the subject invention places an emphasis on increasing the case strength and the core fracture toughness, as well as increasing the thermal stability up to 450° C. to provide hot hardness in high-temperature excursions. U.S. Pat. No. 6,464,801 also discloses case-hardened steels. However, the embodiment A1 of U.S. Pat. No. 6,464,801 shows limited surface-hardness, i.e., Rockwell C scale hardness (HRC) of 60-62. Another embodiment of U.S. Pat. No. 6,464,801, steel C3, shows a greater surface hardness of 69 HRC, but the core of this steel lacks toughness. To be usable as a gear, the core fracture toughness of the steel must exceed 50 ksi√in. Thus, there has developed a need for a carburized gear steel with a surface hardness of HRC of at least about 62-64 at a usable core toughness exceeding 50 ksi√in.
SUMMARY OF THE INVENTION
Briefly, the present invention comprises a high-performance gear steel which is especially useful for rotorcraft transmissions. The steel exhibits an increase in surface hardness and core fracture toughness compared to conventional carburized gear steels. The steel is designed for a reasonable carbide solvus temperature, which, in turn, enables gas or vacuum carburization. Upon gas quenching from the solution heat treatment temperature, the steel transforms into a predominantly lath martensitic matrix. During tempering, an optimal strengthening dispersion of secondary M 2 C carbide precipitates, where M is Mo, Cr, W and/or V. The high tempering temperature of the steel enables higher operating temperatures in transmission components compared to conventional gear steels like X53 or 9310.
To achieve high core toughness, the matrix composition is carefully balanced to ensure the ductile-to-brittle transition is sufficiently below room temperature. The designed composition also effectively limits the thermodynamic driving force for precipitation of embrittling Topologically-Close-Packed (TCP) intermetallic phases such as σ and μ. Toughness of the invented steel is further enhanced by the distribution of a fine dispersion of grain-pinning particles that are stable during carburization and solution heat treatment cycles. The grain-pinning particles are MC carbides, where M=Ti, Nb, Zr, V with Ti preferred, that dissolve during homogenization and subsequently precipitate during forging.
TABLE I
wt %
Alloy
Fe
Cr
Co
Mo
Ni
V
W
C
Ti
Mn
Si
Cu
C64
Bal.
3.5
16.3
1.75
7.5
0.02
0.2
0.11
0.03
Al
Bal.
3.5
18.0
1.10
9.5
0.08
0.0
0.20
0.03
C2
Bal.
4.8
25.0
0.03
3.8
0.06
0.0
0.237
C3
Bal.
5.0
28.0
1.75-2.50
3.25-3.15
0.025
0.0
0.05-0.18
C69B
Bal.
4.5
16.1
1.80
4.3
0.10
0.1
0.12
0.02
X53
Bal.
1.0
0.0
3.25
2.00
0.10
0.0
0.10
0.35
1.00
2.00
9310
Bal.
1.2
0.115
3.25
0.145
0.55
0.25
The exemplary steel of the invention is designated as C64 in the above table. By virtue of inclusion of W, this steel is distinct from the steels disclosed in U.S. Pat. No. 6,464,801 (i.e. A1, C2, and C3). Inclusion of W increases the M 2 C driving force similar to Cr or Mo, and uniquely limits the thermodynamic driving force for precipitation of undesirable TCP phases. Whereas Mo and Cr preferentially promote σ-phase more than μ-phase, W provides a reverse effect. Thus, by adding W, the total driving force for σ- and μ-phases is balanced and precipitation of either TCP phase is avoided.
Alloy C69B is a counterexample. Although alloy C69B does include W and successfully tends to avoid the precipitation of TCP phases, insufficient Ni in the matrix places the ductile-to-brittle transition above room temperature. The Ni content is thus greater in alloys of the embodiment of the invention to place the ductile-to-brittle transition below room temperature and concurrently maximize the driving force for M 2 C, enabling the highest surface hardness at a usable toughness compared to any other known secondary-hardening steel.
Due to high surface hardness, good core toughness, and the high-temperature capability, the disclosed steel is considered especially utilitarian with respect to gears for helicopter transmissions. Other uses of the steel include vehicle gearing and armor. With respect to the constituents in the exemplary steel set forth above, the alloy preferably includes a variance in the constituents in the range of plus or minus five percent of the mean value.
BRIEF DESCRIPTION OF THE DRAWING
In the detailed description which follows, reference will be made to the drawing comprised of the following figures:
FIG. 1 is a systems design chart representing the interactions among the desired hierarchical microstructure, the required processing and the property objectives for the alloy of the invention.
FIG. 2 schematically illustrates the time-temperature processing steps for the subject alloy.
FIG. 3 is a graph plotting the maximum surface hardness and core fracture toughness of various steels possibly useful for power transmission gears. Typical embodiments of the claimed invention are also plotted and identified as alloy C64.
FIG. 4 is a graph plotting the Charpy V-Notch (CVN) impact energy of alloys C64 and C69B, in solid and open circles respectively, at various test temperatures.
FIG. 5 is a graph depicting the hardness profile achieved for the carburized sample of alloy C64 and the alloy A1 of U.S. Pat. No. 6,464,801, in solid and open circles, respectively.
DESCRIPTION OF THE PREFERRED EMBODIMENT
In general, the subject matter of the invention comprises a secondary-hardening carburized gear steel with surface hardness of HRC of at least about 62-64 and core fracture toughness greater than about 50 ksi√in. The interactions among the desired hierarchical microstructure, the processing and the property objectives are represented by the systems design chart in FIG. 1 . An ultimate goal of this invention was to optimize the whole system by controlling each subsystem and provide the most useful combination of surface hardness, core fracture toughness, and temperature resistance.
Failure modes in gears are generally grouped into three categories: bending fatigue, contact fatigue, and temperature-induced scoring. Bending fatigue as well as contact fatigue can be limited by a high surface-hardness. To achieve high surface-hardness, the steel of the invention employs efficient secondary hardening by coherent M 2 C carbides which precipitate during tempering. The high Co content of the steel retards dislocation recovery and reduces the density of dislocations in response to thermal exposure. M 2 C carbides precipitate coherently on these dislocations during tempering and provide a strong secondary hardening response, enabling a surface hardness of 62-64 HRC.
The steel alloy of the invention also limits temperature-induced scoring. Subsurface scoring results if the alloy's contact fatigue strength drops below the applied stress at any point below the surface. To provide adequate fatigue strength and avoid subsurface scoring, typically at least about a 1 mm-deep hardened case is preferred. The steel of the invention achieves this desirable case depth via a carbon content gradient achieved during carburization.
The steel comprises a predominantly lath martensitic matrix free of TCP-phases, and is strengthened by a fine-scale distribution of M 2 C carbides. In order to produce a predominantly lath martensitic matrix, the martensite-start temperature (M s ) must be higher than about 100° C. at the carburized surface. To this end, the invention has a carefully optimized the Ni content. While Ni is desirable for cleavage resistance, it also stabilizes austenite and thus, depresses M s . The Ni content is chosen to place the ductile-to-brittle transition of the steel sufficiently below room temperature, preferably below −20° C., while maintaining a sufficiently high M s . The Ductile-to-Brittle Transition Temperature (DBTT) of the steel can be characterized by measuring the CVN impact energy at varying temperatures. As shown in FIG. 3 , while earlier prototype alloy C69B shows susceptibility to cleavage up to 150° C., the optimized composition of alloy C64 of the invention successfully depresses the DBTT to about −20° C.
To further enhance toughness, the average grain diameter must be less than about 50μ. To prevent undesirable grain growth during solution treatment, the steel employs a grain-pinning dispersion of MC particles, where M may be Ti, Nb, Zr, or V, with Ti preferred. To improve the grain-pinning efficiency, the particle size of the grain-pinning dispersion should be refined. A refined size of the MC particles is achieved by designing a system wherein the particles dissolve during homogenization and subsequently precipitate during forging. The MC particles remain stable during subsequent carburization and solution heat treatment cycles.
The resulting lath martensitic matrix is free of undesirable TCP-phases. TCP-phase precipitation is to be avoided during tempering because such phases can reduce the alloy ductility and toughness. The thermodynamic driving force for precipitation of TCP phases is limited in the invention by the contents of Cr, Mo, and W.
Following are examples of the experiments relating to development of the alloy of the invention:
Example 1
A 3,000-lb vacuum induction melt of Fe-16.1Co-4.5Cr-4.3Ni-1.8Mo-0.12C-0.1V-0.1W-0.02Ti (wt %) was prepared from high purity materials. The melt was converted to a 1.5-inch-square bar. The optimum processing condition was to solutionize at 1050° 90 minutes, quench with oil, immerse in liquid nitrogen for 1 hour, warm in air to room temperature, temper at 468° C. for 56 hours, and cool in air. The DBTT in this condition was between 150° C. and 250° C.
Example 2
A 30-lb vacuum induction melt of Fe-17.0Co-7.0Ni-3.5Cr-1.5Mo-0.2W-0.12C-0.03Ti (wt %) was prepared from high purity materials. M s of the case material was measured as 162° C. from dilatometry, in agreement with model predictions. The carburization response of this prototype was determined from hardness measurements. The optimum processing condition was to carburize and concurrently solutionize the steel at 927° C. for 1 hour, quench with oil, and immerse in liquid nitrogen. A subsequent tempering at 482° C. for 16 hours resulted in a surface-hardness of 62.5 HRC. The case depth of the carburized sample was about 1 mm. An atom-probe tomography analysis of the steel verified the absence of TCP phases.
Example 3
A 300-lb vacuum induction melt of Fe-17.0Co-7.0Ni-3.5Cr-1.5Mo-0.2W-0.12C (wt %) was prepared from high purity materials. Because this prototype did not include Ti, the grain-pinning dispersion of TiC particles could not form. As a result, the average grain diameter was 83μ and toughness was very low. The CVN impact energy of the core material from this prototype was 5 ft-lb at an Ultimate Tensile Strength (UTS) of 238 ksi.
Example 4
A second 300-lb vacuum induction melt of Fe-17.0Co-7.0Ni-3.5Cr-1.5Mo-0.2W-0.12C-0.03Ti (wt %) was prepared from high purity materials. This composition did include Ti, and the average grain diameter was 35μ. Toughness improved substantially. The CVN impact energy of the core material from this prototype was 23 ft·lb at a UTS of 238 ksi. The corresponding processing condition was to carburize and concurrently solutionize the steel at 927° C. for 8 hours, quench with oil, immerse in liquid nitrogen for 1 hour, temper at 496° C. for 8 hours, and cool in air. The fracture toughness in this condition was 100 ksi√in. The DBTT in this condition was around room temperature.
Example 5
A 10,000-lb vacuum induction melt of Fe-16.3Co-7.5Ni-3.5Cr-1.75Mo-0.2W-0.11C-0.03Ti-0.02V (wt %) was prepared from high purity materials. Half of the melt was converted to a 6.5-inch-diameter barstock, while the other half was converted to a 4.5-inch-diameter barstock. The optimum processing condition was to carburize the steel at 927° C. for 3 hours, cool in air, solutionize at 1000° C. for 40 minutes, quench with oil, immerse in liquid nitrogen for 2 hours, warm in air to room temperature, temper at 496° C. for 8 hours, and cool in air. The average grain diameter in this condition was 27μ and the fracture toughness was 85 ksi√in at a UTS of 228 ksi.
TABLE II
1
2
3
4
5 (C64)
C
0.12
0.12
0.12
0.12
0.11
Co
16.1
17.0
17.0
17.0
16.3
Cr
4.5
3.5
3.5
3.5
3.5
Ni
4.3
7.0
7.0
7.0
7.5
Mo
1.8
1.5
1.5
1.5
1.75
V
0.1
0.02
W
0.1
0.2
0.2
0.2
0.2
Ti
0.02
0.03
0.03
0.03
Fe
Bal.
Bal.
Bal.
Bal.
Bal.
Average Grain
83
35
27
Diameter (μ)
TCP
Absent
Absent
Absent
Absent
Absent
Fracture
100
85
Toughness
ksi√in
UTS
238
238
228
HRC
62.5
DBTT (° C.)
150-250
25
Table II summarizes the information with respect to the examples set forth above and also indicates an embodiment of the invention (alloy C64). While an embodiment of the invention is disclosed, it is to be understood that the invention is to be limited only by the following claims and equivalents thereof. | A case hardened gear steel having enhanced core fracture toughness includes by weight percent about 16.3Co, 7.5Ni, 3.5Cr, 1.75Mo, 0.2W, 0.11C, 0.03Ti, and 0.02V and the balance Fe, characterized as a predominantly lath martensitic microstructure essentially free of topologically close-packed (TCP) phases and carburized to include fine M 2 C carbides to provide a case hardness of at least about 62 HRC and a core toughness of at least about 50 ksi√in. | 2 |
FIELD OF THE INVENTION
The present invention relates to a filter element to be used in a filtering apparatus for filtering a fluid.
DESCRIPTION OF THE RELATED ART
Conventionally, as a filter element to be attached to the filtering apparatus for filtering a fluid, various kinds of filter elements having various structures are known.
Filter elements as described above are, however, generally disposable type, and even though they are reusable by cleaning, much time and effort is required to recover them because it is hard to remove foreign materials deposited thereon, or sometimes they have to be soaked into a specific chemical agent for a long time to remove the same.
Therefore, it would be desirable if foreign materials deposited on a filter element can be easily removed and thus the filter element is easily recovered for reuse.
DISCLOSURE OF THE INVENTION
An object of the present invention is to provide filter elements with enhanced ease-of-handle features and excellent usability which can filter out foreign materials to be removed from a fluid satisfactorily and from which deposited foreign materials blocking the filtration gaps can be easily washed out in a short period of time.
In order to achieve above described challenge, according to the present invention, a filter element comprising a cylindrical filter medium and a holder for holding the filter medium is provided. The filter medium is constructed to be resiliently expandable in the direction of axis and to be subject to deformation of the filtration gaps in varying sizes in accordance with the expansion thereof. The filter medium includes a compression limiting means for providing required filtering gaps by limiting the amount of compression applied to the filter medium, and is held by the holder in such a manner that the amount of compression can be adjusted.
According to the present invention, the filter medium is made of a hard resilient material having no compressibility in itself.
According to a detailed embodiment of the present invention, the filter medium is formed by winding a resilient wire rod in a helical fashion including filtration gaps between adjacent wound portions and a plurality of notches for providing the filtration gaps between adjacent wound portions. The notches may be formed by bending parts of the resilient wire rod.
According to another detailed embodiment of the present invention, the filter medium is formed by stacking a plurality of annular resilient plates, and each plate has a plurality of spring portions for resiliently widening the space between adjacent plates and a plurality of projections for providing filtering gaps between adjacent plates when the filter medium is under compression. The spring portions and projections may be formed by making incisions on the plate and raising them up.
According to still another detailed embodiment of the present invention, the filter medium is formed by stacking a plurality of annular spring members and a plurality of annular gap forming members alternately in layers. The spring members are corrugated in the direction of their thickness to be resiliently deformed into the shape of flat plates when the filter medium is under compression. The gap forming members is provided with a plurality of radially extending filtration channels thereon. The filtration channels may be formed on both front and back surfaces of the gap forming members.
The filter element according to the present invention, having structure described so far, is provided with required filtration gaps in the state that the filter medium is compressed to ensure that a fluid is filtered through these filtration gaps. In order to release the compressed state of the filter medium for cleaning, the filtration gaps can be expanded sufficiently by manual operation, by means such as an actuator, or by resilience of a resilient wire rod and/or resilient plates which constitute the filter medium, so that foreign materials deposited on the filter element may be removed easily and satisfactory.
In other words, in the case where the filter medium is configured in the form of coil by a resilient wire rod, when it is under compression, the filtration gaps are provided by notches formed on the resilient wire rod, and when it is removed from the filtering apparatus, the resilient wire rod is expanded because the filter medium is released from compressed state and thus the filtration gaps widen more or less uniformly.
In the case where the filter medium is configured by annular resilient plates, when it is under compression, the filtration gaps in constant widths are provided by means of projections formed on the respective plates, and when it is released from the compressed state, the filtration gaps provided between adjacent plates is widened by spring portions formed on the respective plates.
In addition, in the case where the filter medium is configured by stacking spring members and gap forming members alternately, when the filter medium is under compression, the spring members are flattened into the shape of plates respectively and then filtration gaps of uniform width are provided by the filtration channels formed on the gap forming members. When compression is released, the filtration gaps are widened by restoration of spring members corrugated in the direction of the thickness.
Since the filtration gaps of the filter element can be easily widened as described above, foreign materials filtered out may easily be removed by cleaning. Especially when the filter medium is formed of separate resilient plates or spring members, or of the gap forming members etc., easier cleaning is ensured because they may be disassembled into pieces for cleaning. In addition, the above mentioned disassembled members may be reassembled with relative ease and thus foreign materials may be removed more easily. With such a structure, the filter element itself is readily recoverable and reusable.
BRIEF DESCRIPTION OF DRAWINGS
FIG. 1 is a sectional side elevation view of a filter element according to the first embodiment of the present invention;
FIG. 2 is a horizontal sectional view of the same filter element;
FIG. 3 is a side elevational view of a resilient wire rod under compression;
FIG. 4 is a side elevational view of the same resilient wire rod in the state where compression is released;
FIG. 5 is a sectional side elevational of a laminated body of plates according to the second embodiment illustrating the compressed state;
FIG. 6 is a plan view of the same laminated body of plates;
FIG. 7 is a sectional side elevational of the same laminated body of plates illustrating the state where compression is released;
FIG. 8 is a sectional side elevational view of a filter element according to the third embodiment;
FIG. 9 is a plan view of the same;
FIG. 10 is a side elevational view of the third embodiment illustrating the state where compression of the laminated body formed of spring members and gap forming members is released;
FIG. 11 is a plan view of the same gap forming member;
FIG. 12 is an enlarged end view of the gap forming member taken on line A—A of FIG. 11; and
FIG. 13 is a plan view of a spring member according to the third embodiment.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring now to the drawings, there are shown some preferred embodiments of a filter element according to the present invention in detail. FIGS. 1-4 show the first embodiment of a filter element of this invention.
A filter element 1 is to be mounted in the filtering apparatus for filtering a fluid, comprising, as shown in FIGS. 1 and 2, a cylindrical filter medium 3 which is resiliently expandable in the direction of axis, and a holder 5 for holding the filter medium 3 in the compressed state.
The filter medium 3 is, as shown in FIG. 2-4, formed by winding a hard resilient wire rod 3 a made of material having no compressibility in itself such as metal or ceramics in a helical fashion, and is provided with a designated number of notches 7 per unit turn formed by locally bending parts of the resilient wire rod 3 a nearly equidistantly. As clearly shown in FIG. 3, the formation of such notches 7 provides filtration gaps corresponding to the height of the notches 7 between adjacent parts of winding when the filter medium 3 is compressed. Therefore, the notches 7 constitute a compression limiting means for providing required filtration gaps by limiting the amount of compression applied to the filter medium 3 . The filter medium 3 is held by the holder 5 with its ends caught between an end plate 13 and a movable plate 15 of the holder 5 .
The holder 5 comprises, as shown in FIGS. 1 and 2, a plurality of guide bars 17 surrounding the filter medium 3 equidistantly, end plates 11 , 13 secured to the both ends of these guide bars, and a movable plate 15 mounted to the guide bars between these end plates 11 , 13 in inserted state and movable only in directions along these guide bars.
The end plate 11 is provided with a cylindrical guide cylinder portion 11 A extending through the center portion of the holder 5 toward the other end plate 13 , and within the guide cylinder portion 11 A, a rotating body 19 having a threaded portion 19 a on its periphery is rotatably received and retained by a C-frame retaining ring. The movable plate 15 is slidably fitted around the outer surface of the guide cylinder portion 11 A of the end plate 11 via a O-ring 23 and has a cylindrical portion 15 A extending toward the same direction as the guide cylinder portion 11 A, and on the inner surface of the end portion of the cylindrical portion 15 A, there is provided a threaded portion 15 a for screwing in the threaded portion 19 a prepared on the outer surface of the rotating body 19 . In this arrangement, by rotating the rotating body 19 , the movable plate 15 may be reciprocated along the guide bars 17 .
By placing the filter medium 3 between the end plate 13 and a movable plate 15 and moving the movable plate 15 toward end plate 13 while rotating the rotating body 19 , the filter medium 3 is compressed until the position where respective notches 7 come into pressing contact with adjacent wound portions, and thereby the filter medium 3 is held by a holder under compression with filtration gaps provided between adjacent wound portions by notches 7 .
Reference numbers 25 and 27 in FIG. 1 denote packings mounted on the outer surfaces of the end plates 11 and 13 , respectively.
In the filter element 1 of the first embodiment having above described structure, filtration gaps of the predetermined widths are provided on its side wall by means of notches 7 formed on a resilient wire rod 3 a (FIG. 3 ), and thereby a fluid flowing between the inside and the outside of a cylindrical filter medium 3 is filtered. When the filter medium 3 is resiliently expanded (FIG. 4) by moving the movable plate 15 away from the end plate 13 along the guide bar 17 while rotating the rotating body 19 in the holder, the filtration gaps may be sufficiently widened.
Therefore, when cleaning the filter element, foreign materials filtered out by the filter element 1 may be removed easily and satisfactory, and thereby the filter element 1 itself may be recovered and reused.
Referring now to FIGS. 5-7, there are shown the second embodiment of the filter element of the present invention. In the filter element of the second embodiment, a filter medium 33 to be held under compression by the holder 5 is formed by stacking a plurality of annular resilient plates 33 A in a cylindrical shape.
Respective plates 33 A are made of a hard material such as metal or ceramics as in the case of the resilient wire rod 3 a, and comprise a plurality of spring portions 33 a for resiliently widening gaps between adjacent plates 33 A and a plurality of projection 33 b as compression limiting means for providing required filtration gaps between adjacent plates 33 A when the filter medium 33 is compressed. These spring portions 33 a and projections 33 b are formed by making evenly spaced incisions on the plate 33 A in the same direction and raising them up. Respective plates 33 A are then stacked on top of each other with the positions of spring portion 33 a of adjacent plates 33 A staggered alternately by half a pitch to form the laminated body 33 .
Since the holder used in the second embodiment may employ the same structure as the first embodiment, FIGS. 1 and 2 may be referred to know the structure of the holder and thus it is not specifically shown in a figure here.
In the filter element of the second embodiment with the structure described above, the filter medium 33 formed by stacking annular plates 33 A is held by the holder 5 under compression as shown in FIG. 5 . At this time, the spring portions 33 a of respective plates 33 A are deformed to the extent where the projections 33 b come into contact with adjacent plates 33 A, and thereby between adjacent plates 33 A, 33 A, there are formed filtration gaps of a width provided by the height of the projections 33 b.
On the other hand, when compression applied to the filter medium 33 is released, as shown in FIG. 7, the filter medium 33 is expanded by resilient restoring force of the spring portions 33 a of respective plates 33 A, and consequently the filtration gaps between adjacent plates 33 A, 33 A are widened almost uniformly.
Accordingly, since the filtration gaps of the filter medium 33 in the filter element may be widened easily, foreign materials filtered out may be removed easily by cleaning.
Especially, the filter medium 33 of the second embodiment is formed of a plurality of plates 33 A which can be disassemble, cleaning may be performed for each individual plate 33 A after disassembling them into pieces, which makes removal of foreign materials by cleaning easier. Moreover, restacking of plates in this case is also easy.
Referring now to FIGS. 8-13, there are shown the third embodiment of the present invention. The filter element 61 of the third embodiment is configured in such a manner that the filter medium 63 to be held by the holder 65 under compression is formed in generally cylindrical shape by stacking a plurality of annular spring members 63 A and a plurality of annular gap forming members 63 B as compression limiting means alternately in layers.
The spring members 63 A are, as seen in FIG. 10 and FIG. 13, corrugated in the direction of thickness so that they may resiliently widen the gaps between adjacent gap forming members 63 B when the filter medium 63 is not compressed, and they may be resiliently deformed into flat plates to come into intimate contact with the gap forming members 63 B when the filter medium 63 is compressed. In FIG. 13, parts 63 c designate upwardly raising convex surfaces, and parts 63 d designates downwardly depressed concave surfaces.
The gap forming members 63 B are, as shown in FIGS. 11 and 12 , have a plurality of radially extending filtration channels 63 b on both front and back surfaces, and the filtration channels on the upper surface 63 b are displaced from the filtration channels on the lower surface 63 b by half a pitch.
On the other hand, the holder 65 is, as shown in FIGS. 8 and 9, comprises two end plates 71 , 73 for catching the filter medium 63 from both sides, a tension bolt 75 for adjusting the distance between these end plates 71 , 73 , and a plurality of guide bars 77 , 78 for supporting the filter medium 63 from inside.
On the inner surfaces of the end plates 71 , 73 , there are provided supporting members 71 A, 73 A. On one supporting member 71 A, one end of the tension bolt 75 is secured by means of nuts 74 a, 74 b, and on the other supporting member 73 A, the other end of the tension bolt 75 is secured by a butterfly nut 74 c, and the tension bolt 75 may be expanded and contracted by rotating the butterfly nut 74 c to adjust the distance between the end plates 71 and 73 .
The guide bars 77 , 78 have a length shorter than the axial length of the holder 65 but longer than a half the axial length thereof, and are mounted to respective end plates 71 , 73 . In other words, the end plate 71 located at the bottom of the holder is provided with guide bars 77 mounted in the direction of the axis of the holder 65 at equiangular intervals, and the upper end plate 73 is provided with other guide bars 78 mounted at equiangular intervals so as not to cause interference with the guide bars 77 . These guide bars 77 , 78 support spring members 63 A and gap forming members 63 B which constitute the filter medium 63 from the inside to maintain their stacked shape.
The filter medium 63 is disposed between the end plates 71 , 73 with the guide bars 77 , 78 inserted into the end plates 71 , 73 , and held between the end plates 71 , 73 under compression by tightening the butterfly nut 74 c and thereby contracting the tension bolt 75 .
In the filter element 61 of the third embodiment having above described structure, when the filter medium 63 formed by stacking annular spring members 63 A and annular gap forming members 63 B alternately is compressed by the holder 65 , the spring members 63 A are flattened and brought into intimate contact with the gap forming members 63 B so that a constant filtration gaps are formed by the filtration channels 63 b provided on both front and back surfaces of the gap forming members 63 B.
On the other hand, when compression applied by the holder 65 is released, the filtration gaps between adjacent gap forming members 63 B are expanded due to restoration of the spring members 63 A into corrugated shape.
The holder 5 of the first and second embodiments and the holder 65 of the third embodiment described above may be used respectively for holding filter medium of other embodiments as well. In other words, the holder 5 may be used also for holding the filter medium 63 of the third embodiment comprising spring members 63 A and gap forming members 63 B, while the holder 65 may be used for holding the filter medium 3 and 33 of the first and second embodiments as well.
Especially when the holder 65 of the third embodiment is used for holding the filter medium 33 of the second embodiment, as shown in FIG. 6, a plurality of recesses 33 c may be provided radially on the inner radius of the plate 33 A so that the guide bars 77 , 78 mounted on the holder 65 may be fitted into these recesses 33 c. In this case, the recesses 33 c are to be formed as many as the number of the guide bars 77 , 78 .
The structure of the holder is not limited to ones illustrated in respective embodiments, and other appropriate structures may be employed as far as they can hold the filter medium under compression.
As described so far, according to the present invention, the filter element which may filter out foreign materials to be removed contained in a fluid satisfactory, and may be cleaned easily in a short period of time for reuse is provided. | A filter medium, which is resiliently expandable in an axial direction and is able to deform the filtration gaps in size in accordance with its expansion, including a compression limiting member for providing required filtration gaps by limiting the amount of compression applied to the filter medium. The filter medium is held by a holder in such a manner that the amount of compression may be adjustable. | 1 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a continuation of U.S. patent application Ser. No. 13/231,586 filed Sep. 13, 2011, the entire contents of which is incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates generally to medical methods, devices, and systems. In particular, the present invention relates to methods, devices, and systems for the endovascular, percutaneous or minimally invasive surgical treatment of bodily tissues, such as tissue approximation or valve repair. More particularly, the present invention relates to repair of valves of the heart and venous valves.
[0004] Surgical repair of bodily tissues often involves tissue approximation and fastening of such tissues in the approximated arrangement. When repairing valves, tissue approximation includes coapting the leaflets of the valves in a therapeutic arrangement which may then be maintained by fastening or fixing the leaflets. Such coaptation can be used to treat regurgitation which most commonly occurs in the mitral valve.
[0005] Mitral valve regurgitation is characterized by retrograde flow from the left ventricle of a heart through an incompetent mitral valve into the left atrium. During a normal cycle of heart contraction (systole), the mitral valve acts as a check valve to prevent flow of oxygenated blood back into the left atrium. In this way, the oxygenated blood is pumped into the aorta through the aortic valve. Regurgitation of the valve can significantly decrease the pumping efficiency of the heart, placing the patient at risk of severe, progressive heart failure.
[0006] Mitral valve regurgitation can result from a number of different mechanical defects in the mitral valve or the left ventricular wall. The valve leaflets, the valve chordae which connect the leaflets to the papillary muscles, the papillary muscles or the left ventricular wall may be damaged or otherwise dysfunctional. Commonly, the valve annulus may be damaged, dilated, or weakened limiting the ability of the mitral valve to close adequately against the high pressures of the left ventricle.
[0007] The most common treatments for mitral valve regurgitation rely on valve replacement or repair including leaflet and annulus remodeling, the latter generally referred to as valve annuloplasty. A recent technique for mitral valve repair which relies on suturing adjacent segments of the opposed valve leaflets together is referred to as the “bow-tie” or “edge-to-edge” technique. While all these techniques can be very effective, they usually rely on open heart surgery where the patient's chest is opened, typically via a sternotomy, and the patient placed on cardiopulmonary bypass. The need to both open the chest and place the patient on bypass is traumatic and has associated high mortality and morbidity. More recently, minimally invasive catheter based procedures have been developed to deliver implantable clips to the incompetent valve. These clips are used to fasten a portion of the valve leaflets together, thereby reducing the regurgitation. While the clips appear to be promising, delivery and deployment of the clip can be challenging. In some situations, it may be challenging to visualize the clip and valve leaflets using techniques such as fluoroscopy and echocardiography. Therefore, improved attachment mechanisms and attachment evaluation methods would be desirable.
[0008] For these reasons, it would be desirable to provide improved methods, devices, and systems for performing the repair of mitral and other cardiac valves. Such methods, devices, and systems should preferably not require open chest access and be capable of being performed either endovascularly, i.e., using devices which are advanced to the heart from a point in the patient's vasculature remote from the heart or by a minimally invasive approach. Further, such devices and systems should provide features which allow easier delivery of fixation devices, as well as repositioning and optional removal of the fixation device prior to fixation to ensure optimal placement. Still more preferably, the methods, devices, and systems would be useful for repair of tissues in the body other than heart valves. At least some of these objectives will be met by the inventions described hereinbelow.
[0009] 2. Description of the Background Art
[0010] Minimally invasive and percutaneous techniques for coapting and modifying mitral valve leaflets to treat mitral valve regurgitation are described in PCT Publication Nos. WO 98/35638; WO 99/00059; WO 99/01377; and WO 00/03759.
[0011] Maisano et al. (1998) Eur. J. Cardiothorac. Surg. 13:240-246; Fucci et al. (1995) Eur. J. Cardiothorac. Surg. 9:621-627; and Umana et al. (1998) Ann. Thorac. Surg. 66:1640-1646, describe open surgical procedures for performing “edge-to-edge” or “bow-tie” mitral valve repair where edges of the opposed valve leaflets are sutured together to lessen regurgitation. Dec and Fuster (1994) N. Engl. J. Med. 331:1564-1575 and Alvarez et al. (1996) J. Thorac. Cardiovasc. Surg. 112:238-247 are review articles discussing the nature of and treatments for dilated cardiomyopathy.
[0012] Mitral valve annuloplasty is described in the following publications. Bach and Bolling (1996) Am. J. Cardiol. 78:966-969; Kameda et al. (1996) Ann. Thorac. Surg. 61:1829-1832; Bach and Bolling (1995) Am. Heart J. 129:1165-1170; and Bolling et al. (1995) 109:676-683. Linear segmental annuloplasty for mitral valve repair is described in Ricchi et al. (1997) Ann. Thorac. Surg. 63:1805-1806. Tricuspid valve annuloplasty is described in McCarthy and Cosgrove (1997) Ann. Thorac. Surg. 64:267-268; Tager et al. (1998) Am. J. Cardiol. 81:1013-1016; and Abe et al. (1989) Ann. Thorac. Surg. 48:670-676.
[0013] Percutaneous transluminal cardiac repair procedures are described in Park et al. (1978) Circulation 58:600-608; Uchida et al. (1991) Am. Heart J. 121: 1221-1224; and Ali Khan et al. (1991) Cathet. Cardiovasc. Diagn. 23:257-262.
[0014] Endovascular cardiac valve replacement is described in U.S. Pat. Nos. 5,840,081; 5,411,552; 5,554,185; 5,332,402; 4,994,077; and 4,056,854. See also U.S. Pat. No. 3,671,979 which describes a catheter for temporary placement of an artificial heart valve.
[0015] Other percutaneous and endovascular cardiac repair procedures are described in U.S. Pat. Nos. 4,917,089; 4,484,579; and 3,874,338; and PCT Publication No. WO 91/01689.
[0016] Thoracoscopic and other minimally invasive heart valve repair and replacement procedures are described in U.S. Pat. Nos. 5,855,614; 5,829,447; 5,823,956; 5,797,960; 5,769,812; and 5,718,725.
BRIEF SUMMARY OF THE INVENTION
[0017] The invention provides devices, systems and methods for tissue approximation and repair at treatment sites. The devices, systems and methods of the invention will find use in a variety of therapeutic procedures, including endovascular, minimally-invasive, and open surgical procedures, and can be used in various anatomical regions, including the abdomen, thorax, cardiovascular system, heart, intestinal tract, stomach, urinary tract, bladder, lung, and other organs, vessels, and tissues. The invention is particularly useful in those procedures requiring minimally-invasive or endovascular access to remote tissue locations, where the instruments utilized must negotiate long, narrow, and tortuous pathways to the treatment site. In addition, many of the devices and systems of the invention are adapted to be reversible and removable from the patient at any point without interference with or trauma to internal tissues.
[0018] In preferred embodiments, the devices, systems and methods of the invention are adapted for fixation of tissue at a treatment site. Exemplary tissue fixation applications include cardiac valve repair, septal defect repair, vascular ligation and clamping, laceration repair and wound closure, but the invention may find use in a wide variety of tissue approximation and repair procedures. In a particularly preferred embodiment, the devices, systems and methods of the invention are adapted for repair of cardiac valves, and particularly the mitral valve, as a therapy for regurgitation. The invention enables two or more valve leaflets to be coapted using an “edge-to-edge” or “bow-tie” technique to reduce regurgitation, yet does not require open surgery through the chest and heart wall as in conventional approaches. Using the devices, systems and methods of the invention, the mitral valve can be accessed from a remote surgical or vascular access point and the two valve leaflets may be coapted using endovascular or minimally invasive approaches. While less preferred, in some circumstances the invention may also find application in open surgical approaches as well. According to the invention, the mitral valve may be approached either from the atrial side (antegrade approach) or the ventricular side (retrograde approach), and either through blood vessels or through the heart wall.
[0019] The devices, systems and methods of the invention are centered on variety of devices which may be used individually or in a variety of combinations to form interventional systems. In preferred embodiments, the interventional system includes a multi-catheter guiding system, a delivery catheter and an interventional device. Each of these components will be discussed herein.
[0020] In a first aspect of the present invention, a system for fixing tissue comprises an implantable tissue fixation device comprising a pair of fixation elements each having a first end, a free end opposite the first end, and an engagement surface therebetween for engaging the tissue. The fixation device further comprises a pair of gripping elements. Each gripping element is moveable with respect to one of the fixation elements and is disposed in opposition to one of the engagement surfaces so as to capture tissue therebetween. The system also comprises a gripper pusher releasably coupled to the implantable fixation device adjacent the pair of gripping elements. The gripper pusher has an expanded configuration and a collapsed configuration. In the expanded configuration the gripper pusher engages the pair of gripping elements and advances the pair of gripping elements toward the engagement surfaces of the fixation elements. In the collapsed configuration the gripper pusher has a reduced radial profile relative to the gripper pusher radial profile in the expanded configuration thereby allowing the pair of gripping elements to move away from the engagement surfaces of the fixation elements.
[0021] The first ends of the fixation elements may be movably coupled together such that the fixation elements are moveable between a closed position and an inverted position. In the closed position, the engagement surfaces may face each other, and in the inverted position the engagement surfaces may face away from each other. Each fixation element may be at least partially concave such that each gripping element is separated from an opposing engagement surface in an undeployed configuration, and each gripping element may be at least partially recessed within a fixation element in a deployed configuration. The fixation elements may be further moveable to an open position between the closed position and the inverted position.
[0022] The gripping elements may be movable independently of the fixation elements. They may be biased toward the engagement surfaces. The gripping elements may be approximately parallel to each other in an undeployed configuration.
[0023] The gripper pusher may comprise a spring element that moves from the collapsed configuration to the expanded configuration when a compressive force is applied thereto. The spring element may comprise a longitudinal axis, and the compressive force may be applied in a direction substantially parallel thereto. The spring element may be resiliently biased to return to the collapsed configuration when the compressive force is released. The spring element may be resiliently biased to return to the expanded configuration. The gripper pusher may comprise two spring elements, or an elongate deflectable arm. The arm may comprise a plurality of peaks or bowed regions. The deflectable arm may be biased to return to the expanded configuration, and proximal retraction of the proximal elements may collapse the deflectable arm from the expanded configuration to the collapsed configuration.
[0024] The gripper pusher may comprise an attachment mechanism for releasably attaching a distal portion of the gripper pusher to the implantable fixation device. The attachment mechanism may comprise a notched region on a distal portion of the gripper pusher, and a boss adjacent a proximal end of the implantable fixation device. The notched region may be sized to accept the boss. The system may further comprise an elongate delivery shaft having a proximal portion and a distal portion. The distal portion of the elongate delivery shaft may be releasably coupled to a proximal portion of the gripper pusher. The gripper pusher may comprise an attachment ring or coupling ring that may be coupled to the proximal portion thereof, and the attachment ring may be slidably disposed over the delivery shaft.
[0025] The system may further comprise an actuation mechanism that may be coupled to the fixation elements, and that is adapted to move the fixation elements between the closed position and the inverted position. The system may also comprise a coupling member for detachably coupling the fixation device to an elongate delivery shaft. A covering may be disposed on the fixation elements that is adapted to promote tissue ingrowth. A coating may be disposed on the fixation elements that is adapted to deliver a therapeutic agent to the treatment tissue.
[0026] In another aspect of the invention, a system for fixing tissue may comprise an implantable tissue fixation device and a first gripper actuator. The implantable tissue fixation device comprises a pair of fixation elements and a pair of gripping elements. The pair of fixation elements comprises a first fixation element and a second fixation element. Each fixation element has a first end, a free end opposite the first end, and an engagement surface therebetween for engaging the tissue. The pair of gripping elements comprises a first gripping element and a second gripping element. The first gripping element is moveable with respect to the first fixation element. The first gripping element is also disposed in opposition to the engagement surface of the first fixation element so as to capture tissue therebetween. Similarly, the second gripping element is moveable with respect to the second fixation element and is disposed in opposition to the engagement surface of the second fixation element so as to capture tissue therebetween. The first gripper actuator is releasably coupled to the implantable fixation device adjacent to the first gripping element. The first gripper actuator has a first configuration and a second configuration. Actuating the first gripper actuator between the first configuration and the second configuration moves the first gripping element with respect to the first fixation element. Typically, the system further comprises a second gripper actuator. The second gripper actuator is releasably coupled to the implantable fixation device adjacent to the second gripping element. The second gripper actuator similarly has a first configuration and a second configuration. Actuating the second gripper actuator between the first configuration and the second configuration moves the second gripping element with respect to the second fixation element. The first gripper actuator and the second gripper actuator are actuatable between their first configurations and their second configurations independently of each other.
[0027] In many embodiments, the first ends are movably coupled together such that the fixation elements are moveable between a closed position and an inverted position. In the closed position, the first ends of the pair of fixation elements have their engagement surfaces facing each other. In the open position, the first ends of the pair of fixation elements have their engagement surfaces facing away from each other. The system may further comprise an actuation mechanism coupled to the fixation elements. The actuation mechanism is adapted to move the fixation elements between the closed position and the inverted position.
[0028] In many embodiments, each fixation element is at least partially concave. By being at least partially concave, each gripping element is separated from an opposing engagement surface in an undeployed configuration and may be at least partially recessed within the fixation element in a deployed configuration. The fixation elements may further be moveable to an open position between the closed position and the inverted position.
[0029] In addition to being independently moveable relative to one another, the gripping elements may be movable independently of the fixation elements. The gripping elements may be biased toward the engagement surfaces. The gripping elements may be approximately parallel to each other in an undeployed configuration.
[0030] In many embodiments, the system further comprises a gripper pusher as described above. The gripper pusher is releasably coupled to the implantable fixation device adjacent the pair of gripping elements. The gripper pusher has an expanded configuration and a collapsed configuration. In the expanded configuration, the gripper pusher engages one or more of the pair of gripping elements and advances one or more of the pair of gripping elements toward the engagement surfaces of the fixation elements. In the collapsed configuration, the gripper pusher has a reduced radial profile relative to the gripper pusher radial profile in the expanded configuration. This reduced radial profile allows the pair of gripping elements to move away from the engagement surfaces of the fixation elements.
[0031] In many embodiments, the first gripper actuator comprises a first wire and the second gripper actuator comprises a second wire. The first wire and the second wire may be substantially flat or have other profiles such as round, square, elliptical, etc. Preferably, the substantially flat sides of the first and second wire are positioned to engage the first and second gripping elements and are biased to bend or flex along the flat side. Thus, as the first and second wires are advanced, they will tend to deflect in the direction toward the first and second gripping elements.
[0032] In many embodiments, at least one of a distal end of the first gripper actuator or a distal end of the second gripper actuator is releasably coupled to the implantation fixation device by a suture knot.
[0033] In many embodiments, the system further comprises an elongate delivery shaft having a proximal portion and a distal portion. The distal portion of the elongate delivery shaft is releasably coupled to a proximal portion of the fixation device. Each of the first and second gripper actuators may comprise distal portions. The distal portions of the first and second gripper actuators may be releasably coupled to at least one of the distal portion of the elongate delivery shaft or the proximal portion of the fixation device. For example, the distal portions of the first gripper actuator and second gripper actuator may each comprise a closed loop or a coiled distal end disposed over at least one of the distal portion of the elongate delivery shaft or the proximal portion of the fixation device.
[0034] In many embodiments, the proximal portion of the fixation device comprises a channel having a pair of notches. The distal portion of the elongate delivery shaft comprises a pair of L-shaped ends resiliently biased to fit into the pair of notches. The distal portion of the elongate delivery shaft is releasably coupled to the proximal portion of the fixation device by placing the pair of L-shaped ends into channel of the fixation device and locking the pair of notches in the channel. The first and second gripper actuators each comprise distal ends. Placing the distal ends of the first and second gripper actuators and coupling the distal portion of the elongate delivery shaft to the proximal portion of the fixation device locks the distal ends of the first and second gripper actuators in place. The first and second gripper actuator may each comprise T-shaped distal ends. The system may further comprise a covering assembly coupled to and disposed over the distal portion of the elongate delivery shaft. The covering assembly comprises an outer slideable section and an inner section having a pair of T-shaped openings. The first and second gripper actuator are releasably coupled to the fixation device by sliding the T-shaped distal ends of the first and second gripper actuators into the pair of the T-shaped opening of the inner section of the covering assembly and sliding the outer slideable section to cover the T-shaped openings.
[0035] In many embodiments, the first and second gripper actuators are releasably coupled to the first and second gripping elements, respectively. The first and second gripping elements may each comprise portions extending radially outward. The system may further comprise first and second holding elements. The first holding element is coupled to the first gripper actuator and releasably coupled to the first gripping element at its portion extending radially outward. The second holding element is coupled to the second gripper actuator and releasably coupled to the second gripping element at its portion extending radially outward. The first and second holding element may comprises a first and second ring, respectively. The rings are disposed over the portions extending radially outward of their respective gripping elements. Alternatively, the first and second holding elements may comprise a first and second clip, respectively. The clips are releasably attached to the portion extending radially outward of their respective gripping elements. The first and second clips may each comprise a pair of legs disposed over the length of their respective gripping elements. The portions extending radially outward of the first and second gripping elements may each have apertures. The first and second gripper actuators may be threaded through the apertures of the radially outward portion of the first and second gripping elements, respectively. The first and second gripper actuators may each comprise an enlarged portion. The diameters of the enlarged portions of the first and second gripper actuator may be greater than that of the aperture of the portion extending radially outward of the first and second gripping elements, respectively, to facilitate moving the first and second gripping elements. The enlarged portions of the first and second gripper actuator may comprises a sleeve disposed over the first and second gripper actuators.
[0036] In many embodiments, the first and second gripper actuator and the second gripper actuator each comprise an actuation line and a release line. Each actuation line may comprise a loop while each release line may comprises a single release cable. The single release cable is threaded through the loop of the actuation line when a gripper actuator is coupled a gripping element. Pulling the single release cable out through the loop of the actuation line allows a gripper actuator to be released from a gripping element.
[0037] The system may further comprise a coupling member for detachably coupling the fixation device to an elongate delivery shaft, a covering on the fixation elements adapted for promoting tissue growth, and/or a coating on the fixation elements adapted for delivering a therapeutic agent.
[0038] Another aspect of the invention provides a method for fixing tissue. An implantable tissue fixation device is provided. The fixation device comprises a pair of fixation elements. Each fixation element has a first end, a free end opposite the first end, and an engagement surface therebetween for engaging the tissue. The fixation device further comprises a pair of gripping elements. Each gripping element is moveable with respect to one of the fixation elements and is disposed in apposition to one of the engagement surfaces so as to capture tissue therebetween. The fixation element is positioned relative to tissue so that the tissue is disposed between the pair of gripping elements and the engagement surfaces of the pair of fixation element. The pair of gripping elements is advanced toward the engagement surfaces of the fixation elements.
[0039] In many embodiments, a gripper pusher releasably coupled to the implantable fixation device adjacent the pair of gripping elements is provided, and the pair of gripping elements is advanced toward the engagement surfaces of the fixation elements by engaging the pair of gripping elements with the gripper pusher. Engaging the pair of gripping elements with the gripper pusher may comprise placing the gripper pusher into an expanded configuration from a collapsed configuration. The gripper pusher may comprise a spring element having a longitudinal axis, and the pair of gripping elements may be engaged with the gripper pusher by applying a compressive force to the spring element in a direction substantially parallel to the longitudinal axis to move the gripper pusher to the expanded configuration. The gripper pusher may be placed into the collapsed configuration from the expanded configuration to reduce the radial profile of the gripper pusher relative to the gripper pusher radial profile in the expanded configuration to allow the pair of gripping elements to move away from the engagement surfaces of the fixation elements.
[0040] In many embodiments, the first ends of the pair of the fixation elements is moved between a closed position to an inverted position. The engagement surfaces face each other when the fixation element is in the closed position and away from each other when the fixation element is in the inverted position. The fixation elements may be moved to an open position between the closed position and the inverted position.
[0041] Another aspect of the invention provides a method of fixing tissue. An implantable tissue fixation device is provided. The fixation device comprises a pair of fixation elements, which comprises a first fixation element and a second fixation element. Each fixation element has a first end, a free end opposite the first end, and an engagement surface therebetween for engaging the tissue. The fixation device further comprises a pair of gripping elements, which comprise a first gripping element and a second gripping element. The first gripping element is disposed in apposition to the engagement surface of the first fixation element. The second gripping element is likewise disposed in apposition to the engagement surface of the second fixation element. The fixation element is positioned relative to tissue so that the tissue is disposed between the first gripping element and the engagement surface of the first fixation element. The tissue is captured between the first gripping element and the engagement surface of the first fixation element by moving the first gripping element with respect to the first fixation element. The position of the second gripping element is maintained with respect to the second fixation element while the first gripping element is moved with respect to the first fixation element.
[0042] In many embodiments, a first gripping element actuator coupled to the first gripping element and a second gripping element actuator coupled to the second gripping element are provided. The tissue between the first gripping element and the engagement surface of the first fixation element may be captured by moving the first gripping element actuator to move the first gripping element. The position of the second gripping element with respect to the second fixation element may be maintained by holding the second gripping element actuator stationary relative to the second gripping element.
[0043] In many embodiments, the captured tissue between the first gripping element and the engagement surface of the first fixation element is released by moving the first gripping element away from the first fixation element. The fixation can then be repositioned relative to the tissue.
[0044] In many embodiments, the fixation element is positioned relative to tissue so that the tissue is disposed between the second gripping element and the engagement surface of the second fixation element. The tissue between the second gripping element and the engagement surface of the second fixation element may be captured by moving the second gripping element with respect to the second fixation element. In some embodiments, the captured tissue between the pair of gripping elements and the engagement surfaces of the pair of fixation elements can be released by moving the pair of gripping elements away from the engagement surfaces of the pair of fixation elements. The fixation can then be repositioned relative to the tissue.
[0045] Other aspects of the nature and advantages of the invention are set forth in the detailed description set forth below, taken in conjunction with the drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0046] FIG. 1 illustrates the left ventricle and left atrium of the heart during systole.
[0047] FIG. 2A illustrates free edges of leaflets in normal coaptation, and FIG. 2B illustrates the free edges in regurgitative coaptation.
[0048] FIGS. 3A-3C illustrate grasping of the leaflets with a fixation device, inversion of the distal elements of the fixation device and removal of the fixation device, respectively.
[0049] FIG. 4 illustrates the position of the fixation device in a desired orientation relative to the leaflets.
[0050] FIGS. 5A-5B and 6 A- 6 B illustrate exemplary embodiments of coupling mechanisms of the instant application.
[0051] FIG. 7 illustrates an embodiment of the fixation device of the present invention.
[0052] FIGS. 8A-8B , 9 A- 9 B, 10 A- 10 B, 11 A- 11 B, and 12 - 14 illustrate the fixation device of FIG. 7 in various possible positions during introduction and placement of the device within the body to perform a therapeutic procedure.
[0053] FIGS. 15A-15H illustrate the fixation device of FIG. 7 with a gripper pusher.
[0054] FIGS. 15I-15V illustrate the fixation device of FIG. 7 with independently actuatable proximal elements.
[0055] FIGS. 15 W 1 - 15 AB 7 illustrate various embodiments of coupling a proximal element line to a proximal element of the fixation device of FIG. 7 .
[0056] FIGS. 15 AC 1 - 15 AC 4 illustrate various control mechanisms of the independently actuatable proximal element lines of the fixation device of FIGS. 15I-15V .
[0057] FIGS. 16A-16C illustrate a covering on the fixation device wherein the device is in various positions.
[0058] FIG. 17 illustrates an embodiment of the fixation device including proximal elements and a locking mechanism.
[0059] FIG. 18 provides a cross-sectional view of the locking mechanism of FIG. 17 .
[0060] FIGS. 19-20 provide a cross-sectional view of the locking mechanism in the unlocked and locked positions respectively.
[0061] FIGS. 21 and 22 A- 22 B illustrate another embodiment of a locking mechanism.
[0062] FIGS. 23 and 24 A- 24 B illustrate yet another embodiment of a locking mechanism.
[0063] FIG. 25 is a perspective view of an embodiment of a delivery catheter for a fixation device.
[0064] FIG. 26 illustrates an embodiment of a fixation device coupled to the distal end of a delivery catheter.
[0065] FIG. 27 illustrates a portion of the shaft of a delivery catheter and a fixation device which is coupleable with the catheter.
[0066] FIGS. 28A-28B illustrate an exemplary embodiment of an actuator rod assembly.
[0067] FIGS. 29A-28B , 30 A- 30 B, 31 A- 31 B, and 32 A- 32 B illustrate layers of an exemplary cable used in the actuator rod of FIGS. 28A-28B .
[0068] FIGS. 33A-33B , 34 A- 34 B, 35 A- 35 B, 36 A- 36 B, and 37 A- 37 B illustrate layers in another exemplary cable used in the actuator rod of FIGS. 28A-28B .
[0069] FIGS. 38-40 are cross-sectional views of embodiments of the shaft of the delivery catheter.
[0070] FIGS. 40A-40B illustrate embodiments of the nose of the shaft of the delivery catheter.
[0071] FIG. 41A-41C illustrate various arrangements of lock lines engaging release harnesses of a locking mechanism.
[0072] FIGS. 42A-42B illustrate various arrangements of proximal element lines engaging proximal elements of a fixation device.
[0073] FIG. 43 illustrates an embodiment of the handle of the delivery catheter.
[0074] FIG. 44 is a cross-sectional view of the main body of the handle.
[0075] FIG. 45 illustrates an embodiment of a lock line handle.
[0076] FIG. 45A illustrates the lock line handle of FIG. 45 positioned within a semi-tube which is disposed within the sealed chamber.
[0077] FIGS. 46A-46B illustrate a mechanism for applying tension to lock lines.
[0078] FIGS. 47 and 47 A- 47 B illustrate features of the actuator rod control and handle.
[0079] FIG. 48 is a perspective view of an embodiment of a multi-catheter guiding system of the present invention, and an interventional catheter positioned therethrough.
[0080] FIG. 49A illustrates a primary curvature in an outer guide catheter.
[0081] FIG. 49B illustrates a secondary curvature in an inner guide catheter.
[0082] FIGS. 49C-49D illustrate example movement of an inner guide catheter through angle thetas.
[0083] FIG. 50A is a perspective side view of a multi-catheter guiding system having an additional curve in the outer guide catheter.
[0084] FIG. 50B illustrates lifting of the outer guide catheter due to the additional curve of FIG. 49A .
[0085] FIGS. 51A-51D illustrate a method of using the multi-catheter guiding system for accessing the mitral valve.
[0086] FIGS. 52A-52D illustrate curvature of a guide catheter of the present invention by the actuation of one or more pullwires.
[0087] FIG. 52E illustrates attachment of a pullwire to a tip ring.
[0088] FIGS. 53A-53I illustrate embodiments of the present invention comprising sections constructed with the inclusion of braiding or a coil.
[0089] FIGS. 54A-54C illustrate a keying feature of the present invention.
[0090] FIGS. 55A-55B are perspective views of a guide catheter including a series of articulating members.
[0091] FIG. 56 illustrates embodiments of the handles.
[0092] FIG. 57 illustrates the handles of FIG. 56 with a portion of the housing removed.
[0093] FIG. 58 illustrates steering mechanisms within a handle.
[0094] FIG. 59 illustrates attachment of a pullwire to a disk.
[0095] FIGS. 60A-60B illustrate a hard stop peg restricting rotation of a disk.
[0096] FIGS. 61A-61C illustrates a portion of a hard stop gear assembly.
[0097] FIGS. 62A-62F illustrate a ball restricting rotation of a disk.
[0098] FIG. 63 illustrates an embodiment of a friction assembly.
[0099] FIG. 64 illustrates an embodiment of an interventional system of the present invention.
[0100] FIG. 64A illustrates an embodiment of a hemostatic valve for use with the present invention.
[0101] FIG. 64B illustrates an embodiment of a fixation device introducer.
[0102] FIG. 65 illustrates another embodiment of an interventional system of the present invention.
[0103] FIGS. 66-68 illustrate an embodiment of a stabilizer base for use with the present invention.
[0104] FIG. 69 illustrates a kit constructed in accordance with the principles of the present invention.
[0105] FIG. 70 illustrates a handle in accordance with an exemplary embodiment.
DETAILED DESCRIPTION OF THE INVENTION
I. Cardiac Physiology
[0106] The left ventricle LV of a normal heart H in systole is illustrated in FIG. 1 . The left ventricle LV is contracting and blood flows outwardly through the tricuspid (aortic) valve AV in the direction of the arrows. Back flow of blood or “regurgitation” through the mitral valve MV is prevented since the mitral valve is configured as a “check valve” which prevents back flow when pressure in the left ventricle is higher than that in the left atrium LA. The mitral valve MV comprises a pair of leaflets having free edges FE which meet evenly to close, as illustrated in FIG. 1 . The opposite ends of the leaflets LF are attached to the surrounding heart structure along an annular region referred to as the annulus AN. The free edges FE of the leaflets LF are secured to the lower portions of the left ventricle LV through chordae tendinae CT (referred to hereinafter as the chordae) which include a plurality of branching tendons secured over the lower surfaces of each of the valve leaflets LF. The chordae CT in turn, are attached to the papillary muscles PM which extend upwardly from the lower portions of the left ventricle and intraventricular septum IVS.
[0107] A number of structural defects in the heart can cause mitral valve regurgitation. Regurgitation occurs when the valve leaflets do not close properly allowing leakage from the ventricle into the atrium. As shown in FIG. 2A , the free edges of the anterior and posterior leaflets normally meet along a line of coaptation C. An example of a defect causing regurgitation is shown in FIG. 2B . Here an enlargement of the heart causes the mitral annulus to become enlarged, making it impossible for the free edges FE to meet during systole. This results in a gap G which allows blood to leak through the valve during ventricular systole. Ruptured or elongated chordae can also cause a valve leaflet to prolapse since inadequate tension is transmitted to the leaflet via the chordae. While the other leaflet maintains a normal profile, the two valve leaflets do not properly meet and leakage from the left ventricle into the left atrium will occur. Such regurgitation can also occur in patients who have suffered ischemic heart disease where the left ventricle does not contract sufficiently to effect proper closure.
II. General Overview
[0108] The present invention provides methods and devices for grasping, approximating and fixating tissues such as valve leaflets to treat cardiac valve regurgitation, particularly mitral valve regurgitation. The present invention also provides features that allow repositioning and removal of the device if so desired, particularly in areas where removal may be hindered by anatomical features such as chordae CT. Such removal would allow the surgeon to reapproach the valve in a new manner if so desired.
[0109] Grasping will preferably be atraumatic providing a number of benefits. By atraumatic, it is meant that the devices and methods of the invention may be applied to the valve leaflets and then removed without causing any significant clinical impairment of leaflet structure or function. The leaflets and valve continue to function substantially the same as before the invention was applied. Thus, some minor penetration or denting of the leaflets may occur using the invention while still meeting the definition of “atraumatic.” This enables the devices of the invention to be applied to a diseased valve and, if desired, removed or repositioned without having negatively affected valve function. In addition, it will be understood that in some cases it may be necessary or desirable to pierce or otherwise permanently affect the leaflets during either grasping, fixing or both. In some of these cases, grasping and fixation may be accomplished by a single device. Although a number of embodiments are provided to achieve these results, a general overview of the basic features will be presented herein. Such features are not intended to limit the scope of the invention and are presented with the aim of providing a basis for descriptions of individual embodiments presented later in the application.
[0110] The devices and methods of the invention rely upon the use of an interventional tool that is positioned near a desired treatment site and used to grasp the target tissue. In endovascular applications, the interventional tool is typically an interventional catheter. In surgical applications, the interventional tool is typically an interventional instrument. In preferred embodiments, fixation of the grasped tissue is accomplished by maintaining grasping with a portion of the interventional tool which is left behind as an implant. While the invention may have a variety of applications for tissue approximation and fixation throughout the body, it is particularly well adapted for the repair of valves, especially cardiac valves such as the mitral valve. Referring to FIG. 3A , an interventional tool 10 , having a delivery device, such as a shaft 12 , and a fixation device 14 , is illustrated having approached the mitral valve MV from the atrial side and grasped the leaflets LF. The mitral valve may be accessed either surgically or by using endovascular techniques, and either by a retrograde approach through the ventricle or by an antegrade approach through the atrium, as described above. For illustration purposes, an antegrade approach is described.
[0111] The fixation device 14 is releasably attached to the shaft 12 of the interventional tool 10 at its distal end. When describing the devices of the invention herein, “proximal” shall mean the direction toward the end of the device to be manipulated by the user outside the patient's body, and “distal” shall mean the direction toward the working end of the device that is positioned at the treatment site and away from the user. With respect to the mitral valve, proximal shall refer to the atrial or upstream side of the valve leaflets and distal shall refer to the ventricular or downstream side of the valve leaflets.
[0112] The fixation device 14 typically comprises proximal elements 16 (or gripping elements) and distal elements 18 (or fixation elements) which protrude radially outward and are positionable on opposite sides of the leaflets LF as shown so as to capture or retain the leaflets therebetween. The proximal elements 16 are preferably comprised of cobalt chromium, nitinol or stainless steel, and the distal elements 18 are preferably comprised of cobalt chromium or stainless steel, however any suitable materials may be used. The fixation device 14 is coupleable to the shaft 12 by a coupling mechanism 17 . The coupling mechanism 17 allows the fixation device 14 to detach and be left behind as an implant to hold the leaflets together in the coapted position.
[0113] In some situations, it may be desired to reposition or remove the fixation device 14 after the proximal elements 16 , distal elements 18 , or both have been deployed to capture the leaflets LF. Such repositioning or removal may be desired for a variety of reasons, such as to reapproach the valve in an attempt to achieve better valve function, more optimal positioning of the device 14 on the leaflets, better purchase on the leaflets, to detangle the device 14 from surrounding tissue such as chordae, to exchange the device 14 with one having a different design, or to abort the fixation procedure, to name a few. To facilitate repositioning or removal of the fixation device 14 the distal elements 18 are releasable and optionally invertible to a configuration suitable for withdrawal of the device 14 from the valve without tangling or interfering with or damaging the chordae, leaflets or other tissue. FIG. 3B illustrates inversion wherein the distal elements 18 are moveable in the direction of arrows 40 to an inverted position. Likewise, the proximal elements 16 may be raised, if desired. In the inverted position, the device 14 may be repositioned to a desired orientation wherein the distal elements may then be reverted to a grasping position against the leaflets as in FIG. 3A . Alternatively, the fixation device 14 may be withdrawn (indicated by arrow 42 ) from the leaflets as shown in FIG. 3C . Such inversion reduces trauma to the leaflets and minimizes any entanglement of the device with surrounding tissues. Once the device 14 has been withdrawn through the valve leaflets, the proximal and distal elements may be moved to a closed position or configuration suitable for removal from the body or for reinsertion through the mitral valve.
[0114] FIG. 4 illustrates the position of the fixation device 14 in a desired orientation in relation to the leaflets LF. This is a short-axis view of the mitral valve MV from the atrial side, therefore, the proximal elements 16 are shown in solid line and the distal elements 18 are shown in dashed line. The proximal and distal elements 16 , 18 are positioned to be substantially perpendicular to the line of coaptation C. The device 14 may be moved roughly along the line of coaptation to the location of regurgitation. The leaflets LF are held in place so that during diastole, as shown in FIG. 4 , the leaflets LF remain in position between the elements 16 , 18 surrounded by openings O which result from the diastolic pressure gradient. Advantageously, leaflets LF are coapted such that their proximal or upstream surfaces are facing each other in a vertical orientation, parallel to the direction of blood flow through mitral valve MV. The upstream surfaces may be brought together so as to be in contact with one another or may be held slightly apart, but will preferably be maintained in the vertical orientation in which the upstream surfaces face each other at the point of coaptation. This simulates the double orifice geometry of a standard surgical bow-tie repair. Color Doppler echo will show if the regurgitation of the valve has been reduced. If the resulting mitral flow pattern is satisfactory, the leaflets may be fixed together in this orientation. If the resulting color Doppler image shows insufficient improvement in mitral regurgitation, the interventional tool 10 may be repositioned. This may be repeated until an optimal result is produced wherein the leaflets LF are held in place.
[0115] Once the leaflets are coapted in the desired arrangement, the fixation device 14 is then detached from the shaft 12 and left behind as an implant to hold the leaflets together in the coapted position. As mentioned previously, the fixation device 14 is coupled to the shaft 12 by a coupling mechanism 17 . FIGS. 5A-5B , 6 A- 6 B illustrate exemplary embodiments of such coupling mechanisms. FIG. 5A shows an upper shaft 20 and a detachable lower shaft 22 which are interlocked at a joining line or mating surface 24 . The mating surface 24 may have any shape or curvature which will allow or facilitate interlocking and later detachment. A snuggly fitting outer sheath 26 is positioned over the shafts 20 , 22 to cover the mating surface 24 as shown. FIG. 5B illustrates detachment of the lower shaft 22 from the upper shaft 20 . This is achieved by retracting the outer sheath 26 , so that the mating surface 24 is exposed, which allows the shafts 20 , 22 to separate.
[0116] Similarly, FIG. 6A illustrates a tubular upper shaft 28 and a detachable tubular lower shaft 30 which are interlocked at a mating surface 32 . Again, the mating surface 32 may have any shape or curvature which will allow or facilitate interlocking and later detachment. The tubular upper shaft 28 and tubular lower shaft 30 form an outer member having an axial channel. A snuggly fitting rod 34 or inner member is inserted through the tubular shafts 28 , 30 to bridge the mating surface 32 as shown. The rod 34 may also be used to actuate the fixation device, such as actuator rod 64 seen in FIG. 26 or actuator rod 64 a illustrated in FIGS. 28A-28B , described below. FIG. 6B illustrates detachment of the lower shaft 30 from the upper shaft 28 . This is achieved by retracting the rod 34 to a position above the mating surface 32 which in turn allows the shafts 28 , 30 to separate. Other examples of coupling mechanisms are described and illustrated in U.S. Pat. No. 6,752,813 (Attorney Docket No. 020489-000400), and U.S. Patent Publication No. 2009/0163934 (Attorney Docket No. 020489-001470US), the entire contents of each of which are incorporated herein by reference for all purposes.
[0117] In a preferred embodiment, mating surface 24 (or mating surface 32 ) is a sigmoid curve defining a male element and female element on upper shaft 20 (or upper shaft 28 ) which interlock respectively with corresponding female and male elements on lower shaft 22 (or lower shaft 30 ). Typically, the lower shaft is the coupling mechanism 17 of the fixation device 14 . Therefore, the shape of the mating surface selected will preferably provide at least some mating surfaces transverse to the axial axis of the a mechanism 19 to facilitate application of compressive and tensile forces through the coupling mechanism 17 to the fixation device 14 , yet causing minimal interference when the fixation device 14 is to be released from the upper shaft.
III. Fixation Device
[0118] A. Introduction and Placement of Fixation Device
[0119] The fixation device 14 is delivered to the valve or the desired tissues with the use of a delivery device. The delivery device may be rigid or flexible depending on the application. For endovascular applications, the delivery device comprises a flexible delivery catheter which will be described in later sections. Typically, however, such a catheter comprises a shaft, having a proximal end and a distal end, and a fixation device releasably attached to its distal end. The shaft is usually elongate and flexible, suitable for intravascular introduction. Alternatively, the delivery device may comprise a shorter and less flexible interventional instrument which may be used for trans-thoracic surgical introduction through the wall of the heart, although some flexibility and a minimal profile will generally be desirable. A fixation device is releasably coupleable with the delivery device as illustrated in FIG. 3A . The fixation device may have a variety of forms, a few embodiments of which will be described herein.
[0120] FIG. 7 illustrates another embodiment of a fixation device 14 . Here, the fixation device 14 is shown coupled to a shaft 12 to form an interventional tool 10 . The fixation device 14 includes a coupling member 19 and a pair of opposed distal elements 18 . The distal elements 18 comprise elongate arms 53 , each arm having a proximal end 52 rotatably connected to the coupling member 19 and a free end 54 . The free ends 54 have a rounded shape to minimize interference with and trauma to surrounding tissue structures. Preferably, each free end 54 defines a curvature about two axes, one being an axis 66 perpendicular to longitudinal axis of arms 53 . Thus, the engagement surfaces 50 have a cupped or concave shape to surface area in contact with tissue and to assist in grasping and holding the valve leaflets. This further allows arms 53 to nest around the shaft 12 in the closed position to minimize the profile of the device. Preferably, arms 53 are at least partially cupped or curved inwardly about their longitudinal axes 66 . Also, preferably, each free end 54 defines a curvature about an axis 67 perpendicular to axis 66 or the longitudinal axis of arms 53 . This curvature is a reverse curvature along the most distal portion of the free end 54 . Likewise, the longitudinal edges of the free ends 54 may flare outwardly. Both the reverse curvature and flaring minimize trauma to the tissue engaged therewith.
[0121] In a preferred embodiment suitable for mitral valve repair, the transverse width across engagement surfaces 50 (which determines the width of tissue engaged) is at least about 2 mm, usually 3-10 mm, and preferably about 4-6 mm. In some situations, a wider engagement is desired wherein the engagement surfaces 50 are larger, for example about 2 cm, or multiple fixation devices are used adjacent to each other. Arms 53 and engagement surfaces 50 are configured to engage a length of tissue of about 4-10 mm, and preferably about 6-8 mm along the longitudinal axis of arms 53 . Arms 53 further include a plurality of openings to enhance grip and to promote tissue ingrowth following implantation.
[0122] The valve leaflets are grasped between the distal elements 18 and proximal elements 16 . In some embodiments, the proximal elements 16 are flexible, resilient, and cantilevered from coupling member 19 . The proximal elements are preferably resiliently biased toward the distal elements. Each proximal element 16 is shaped and positioned to be at least partially recessed within the concavity of the distal element 18 when no tissue is present. When the fixation device 14 is in the open position, the proximal elements 16 are shaped such that each proximal element 16 is separated from the engagement surface 50 near the proximal end 52 of arm 53 and slopes toward the engagement surface 50 near the free end 54 with the free end of the proximal element contacting engagement surface 50 , as illustrated in FIG. 7 . This shape of the proximal elements 16 accommodates valve leaflets or other tissues of varying thicknesses.
[0123] Proximal elements 16 include a plurality of openings 63 and scalloped side edges 61 to increase grip on tissue. The proximal elements 16 optionally include frictional accessories, frictional features or grip-enhancing elements to assist in grasping and/or holding the leaflets. In preferred embodiments, the frictional accessories comprise barbs 60 having tapering pointed tips extending toward engagement surfaces 50 . It may be appreciated that any suitable frictional accessories may be used, such as prongs, windings, bands, barbs, grooves, channels, bumps, surface roughening, sintering, high-friction pads, coverings, coatings or a combination of these. Optionally, magnets may be present in the proximal and/or distal elements. It may be appreciated that the mating surfaces will be made from or will include material of opposite magnetic charge to cause attraction by magnetic force. For example, the proximal elements and distal elements may each include magnetic material of opposite charge so that tissue is held under constant compression between the proximal and distal elements to facilitate faster healing and ingrowth of tissue. Also, the magnetic force may be used to draw the proximal elements 16 toward the distal elements 18 , in addition to or alternatively to biasing of the proximal elements toward the distal elements. This may assist in deployment of the proximal elements 16 . In another example, the distal elements 18 each include magnetic material of opposite charge so that tissue positioned between the distal elements 18 is held therebetween by magnetic force. Actuation of the proximal elements may also be accomplished using one or more proximal element lines or actuators such as those described below.
[0124] The proximal elements 16 may be covered with a fabric or other flexible material as described below to enhance grip and tissue ingrowth following implantation. Preferably, when fabrics or coverings are used in combination with barbs or other frictional features, such features will protrude through such fabric or other covering so as to contact any tissue engaged by proximal elements 16 .
[0125] In an exemplary embodiment, proximal elements 16 are formed from metallic sheet of a spring-like material using a stamping operation which creates openings 63 , scalloped edges 61 and barbs 60 . Alternatively, proximal elements 16 could be comprised of a spring-like material or molded from a biocompatible polymer. It should be noted that while some types of frictional accessories that can be used in the present invention may permanently alter or cause some trauma to the tissue engaged thereby, in a preferred embodiment, the frictional accessories will be atraumatic and will not injure or otherwise affect the tissue in a clinically significant way. For example, in the case of barbs 60 , it has been demonstrated that following engagement of mitral valve leaflets by fixation device 14 , should the device later be removed during the procedure barbs 60 leave no significant permanent scarring or other impairment of the leaflet tissue and are thus considered atraumatic.
[0126] The fixation device 14 also includes an actuation mechanism 58 . In this embodiment, the actuation mechanism 58 comprises two link members or legs 68 , each leg 68 having a first end 70 which is rotatably joined with one of the distal elements 18 at a riveted joint 76 and a second end 72 which is rotatably joined with a stud 74 . The legs 68 are preferably comprised of a rigid or semi-rigid metal or polymer such as Elgiloy®, cobalt chromium or stainless steel, however any suitable material may be used. While in the embodiment illustrated both legs 68 are pinned to stud 74 by a single rivet 78 , it may be appreciated, however, that each leg 68 may be individually attached to the stud 74 by a separate rivet or pin. The stud 74 is joinable with an actuator rod 64 (not shown) which extends through the shaft 12 and is axially extendable and retractable to move the stud 74 and therefore the legs 68 which rotate the distal elements 18 between closed, open and inverted positions. Likewise, immobilization of the stud 74 holds the legs 68 in place and therefore holds the distal elements 18 in a desired position. The stud 74 may also be locked in place by a locking feature which will be further described in later sections.
[0127] In any of the embodiments of fixation device 14 disclosed herein, it may be desirable to provide some mobility or flexibility in distal elements 18 and/or proximal elements 16 in the closed position to enable these elements to move or flex with the opening or closing of the valve leaflets. This provides shock absorption and thereby reduces force on the leaflets and minimizes the possibility for tearing or other trauma to the leaflets. Such mobility or flexibility may be provided by using a flexible, resilient metal or polymer of appropriate thickness to construct the distal elements 18 . Also, the locking mechanism of the fixation device (described below) may be constructed of flexible materials to allow some slight movement of the proximal and distal elements even when locked. Further, the distal elements 18 can be connected to the coupling mechanism 19 or to actuation mechanism 58 by a mechanism that biases the distal element into the closed position (inwardly) but permits the arms to open slightly in response to forces exerted by the leaflets. For example, rather than being pinned at a single point, these components may be pinned through a slot that allowed a small amount of translation of the pin in response to forces against the arms. A spring is used to bias the pinned component toward one end of the slot.
[0128] FIGS. 8A-8B , 9 A- 9 B, 10 A- 10 B, 11 A- 11 B, and FIGS. 12-14 illustrate embodiments of the fixation device 14 of FIG. 7 in various possible positions during introduction and placement of the device 14 within the body to perform a therapeutic procedure. FIG. 8A illustrates an embodiment of an interventional tool 10 delivered through a catheter 86 . It may be appreciated that the interventional tool 10 may take the form of a catheter, and likewise, the catheter 86 may take the form of a guide catheter or sheath. However, in this example the terms interventional tool 10 and catheter 86 will be used. The interventional tool 10 comprises a fixation device 14 coupled to a shaft 12 and the fixation device 14 is shown in the closed position. FIG. 8B illustrates a similar embodiment of the fixation device of FIG. 8A in a larger view. In the closed position, the opposed pair of distal elements 18 are positioned so that the engagement surfaces 50 face each other. Each distal element 18 comprises an elongate arm 53 having a cupped or concave shape so that together the arms 53 surround the shaft 12 and optionally contact each other on opposite sides of the shaft. This provides a low profile for the fixation device 14 which is readily passable through the catheter 86 and through any anatomical structures, such as the mitral valve. In addition, FIG. 8B further includes an actuation mechanism 58 . In this embodiment, the actuation mechanism 58 comprises two legs 68 which are each movably coupled to a base 69 . The base 69 is joined with an actuator rod 64 which extends through the shaft 12 and is used to manipulate the fixation device 14 . In some embodiments, the actuator rod 64 attaches directly to the actuation mechanism 58 , particularly the base 69 . However, the actuator rod 64 may alternatively attach to a stud 74 which in turn is attached to the base 69 . In some embodiments, the stud 74 is threaded so that the actuator rod 64 attaches to the stud 74 by a screw-type action. However, the rod 64 and stud 74 may be joined by any mechanism which is releasable to allow the fixation device 14 to be detached from shaft 12 . Other aspects of the actuator rod and its coupling with the fixation device are disclosed below.
[0129] FIGS. 9A-9B illustrate the fixation device 14 in the open position. In the open position, the distal elements 18 are rotated so that the engagement surfaces 50 face a first direction. Distal advancement of the stud 74 relative to coupling member 19 by action of the actuator rod 64 applies force to the distal elements 18 which begin to rotate around joints 76 due to freedom of movement in this direction. Such rotation and movement of the distal elements 18 radially outward causes rotation of the legs 68 about joints 80 so that the legs 68 are directed slightly outwards. The stud 74 may be advanced to any desired distance correlating to a desired separation of the distal elements 18 . In the open position, engagement surfaces 50 are disposed at an acute angle relative to shaft 12 , and are preferably at an angle of between 90 and 180 degrees relative to each other. In one embodiment, in the open position the free ends 54 of arms 53 have a span therebetween of about 10-20 mm, usually about 12-18 mm, and preferably about 14-16 mm.
[0130] Proximal elements 16 are typically biased outwardly toward arms 53 . The proximal elements 16 may be moved inwardly toward the shaft 12 and held against the shaft 12 with the aid of proximal element lines 90 which can be in the form of sutures, wires, nitinol wire, rods, cables, polymeric lines, or other suitable structures. The proximal element lines 90 may be connected with the proximal elements 16 by threading the lines 90 in a variety of ways. When the proximal elements 16 have a loop shape, as shown in FIG. 9A , the line 90 may pass through the loop and double back. When the proximal elements 16 have an elongate solid shape, as shown in FIG. 9B , the line 90 may pass through one or more of the openings 63 in the element 16 . Further, a line loop 48 may be present on a proximal element 16 , also illustrated in FIG. 9B , through which a proximal element line 90 may pass and double back. Such a line loop 48 may be useful to reduce friction on proximal element line 90 or when the proximal elements 16 are solid or devoid of other loops or openings through which the proximal element lines 90 may attach. A proximal element line 90 may attach to the proximal elements 16 by detachable means which would allow a single line 90 to be attached to a proximal element 16 without doubling back and would allow the single line 90 to be detached directly from the proximal element 16 when desired. Examples of such detachable means include hooks, snares, clips or breakable couplings, to name a few. By applying sufficient tension to the proximal element line 90 , the detachable means may be detached from the proximal element 16 such as by breakage of the coupling. Other mechanisms for detachment may also be used. Similarly, a lock line 92 may be attached and detached from a locking mechanism by similar detachable means.
[0131] In the open position, the fixation device 14 can engage the tissue which is to be approximated or treated. The embodiment illustrated in FIGS. 7-9B is adapted for repair of the mitral valve using an antegrade approach from the left atrium. The interventional tool 10 is advanced through the mitral valve from the left atrium to the left ventricle. The distal elements 18 are oriented to be perpendicular to the line of coaptation and then positioned so that the engagement surfaces 50 contact the ventricular surface of the valve leaflets, thereby grasping the leaflets. The proximal elements 16 remain on the atrial side of the valve leaflets so that the leaflets lie between the proximal and distal elements. In this embodiment, the proximal elements 16 have frictional accessories, such as barbs 60 which are directed toward the distal elements 18 . However, neither the proximal elements 16 nor the barbs 60 contact the leaflets at this time.
[0132] The interventional tool 10 may be repeatedly manipulated to reposition the fixation device 14 so that the leaflets are properly contacted or grasped at a desired location. Repositioning is achieved with the fixation device in the open position. In some instances, regurgitation may also be checked while the device 14 is in the open position. If regurgitation is not satisfactorily reduced, the device may be repositioned and regurgitation checked again until the desired results are achieved.
[0133] It may also be desired to invert the fixation device 14 to aid in repositioning or removal of the fixation device 14 . FIGS. 10A-10B illustrate the fixation device 14 in the inverted position. By further advancement of stud 74 relative to coupling member 19 , the distal elements 18 are further rotated so that the engagement surfaces 50 face outwardly and free ends 54 point distally, with each arm 53 forming an obtuse angle relative to shaft 12 . The angle between arms 53 is preferably in the range of about 270 to 360 degrees. Further advancement of the stud 74 further rotates the distal elements 18 around joints 76 . This rotation and movement of the distal elements 18 radially outward causes rotation of the legs 68 about joints 80 so that the legs 68 are returned toward their initial position, generally parallel to each other. The stud 74 may be advanced to any desired distance correlating to a desired inversion of the distal elements 18 . Preferably, in the fully inverted position, the span between free ends 54 is no more than about 20 mm, usually less than about 16 mm, and preferably about 12-14 mm. In this illustration, the proximal elements 16 remain positioned against the shaft 12 by exerting tension on the proximal element lines 90 . Thus, a relatively large space may be created between the elements 16 , 18 for repositioning. In addition, the inverted position allows withdrawal of the fixation device 14 through the valve while minimizing trauma to the leaflets. Engagement surfaces 50 provide an atraumatic surface for deflecting tissue as the fixation device is retracted proximally. It should be further noted that barbs 60 are angled slightly in the distal direction (away from the free ends of the proximal elements 16 ), reducing the risk that the barbs will catch on or lacerate tissue as the fixation device is withdrawn.
[0134] Once the fixation device 14 has been positioned in a desired location against the valve leaflets, the leaflets may then be captured between the proximal elements 16 and the distal elements 18 . FIGS. 11A-11B illustrate the fixation device 14 in such a position. Here, the proximal elements 16 are lowered toward the engagement surfaces 50 so that the leaflets are held therebetween. In FIG. 11B , the proximal elements 16 are shown to include barbs 60 which may be used to provide atraumatic gripping of the leaflets. Alternatively, larger, more sharply pointed barbs or other penetration structures may be used to pierce the leaflets to more actively assist in holding them in place. This position is similar to the open position of FIGS. 9A-9B , however the proximal elements 16 are now lowered toward arms 53 by releasing tension on proximal element lines 90 to compress the leaflet tissue therebetween. At any time, the proximal elements 16 may be raised and the distal elements 18 adjusted or inverted to reposition the fixation device 14 , if regurgitation is not sufficiently reduced.
[0135] After the leaflets have been captured between the proximal and distal elements 16 , 18 in a desired arrangement, the distal elements 18 may be locked to hold the leaflets in this position or the fixation device 14 may be returned to or toward a closed position. Such locking will be described in a later section. FIG. 12 illustrates the fixation device 14 in the closed position wherein the leaflets (not shown) are captured and coapted. This is achieved by retraction of the stud 74 proximally relative to coupling member 19 so that the legs 68 of the actuation mechanism 58 apply an upwards force to the distal elements 18 which in turn rotate the distal elements 18 so that the engagement surfaces 50 again face one another. The released proximal elements 16 which are biased outwardly toward distal elements 18 are concurrently urged inwardly by the distal elements 18 . The fixation device 14 may then be locked to hold the leaflets in this closed position as described below.
[0136] As shown in FIG. 13 , the fixation device 14 may then be released from the shaft 12 . As mentioned, the fixation device 14 is releasably coupleable to the shaft 12 by coupling member 19 (best seen in FIG. 17 ). FIG. 13 illustrates the coupling structure, a portion of the shaft 12 to which the coupling member 19 of the fixation device 14 attaches. As shown, the proximal element lines 90 may remain attached to the proximal elements 16 following detachment from shaft 12 to function as a tether to keep the fixation device 14 connected with the catheter 86 . Optionally, a separate tether coupled between shaft 12 and fixation device 14 may be used expressly for this purpose while the proximal element lines 90 are removed. In any case, the repair of the leaflets or tissue may be observed by non-invasive visualization techniques, such as echocardiography, to ensure the desired outcome. If the repair is not desired, the fixation device 14 may be retrieved with the use of the tether or proximal element lines 90 so as to reconnect coupling member 19 with shaft 12 .
[0137] In an exemplary embodiments, proximal element lines 90 are elongated flexible threads, wire, cable, sutures or lines extending through shaft 12 , looped through proximal elements 16 , and extending back through shaft 12 to its proximal end. When detachment is desired, one end of each line may be released at the proximal end of the shaft 12 and the other end pulled to draw the free end of the line distally through shaft 12 and through proximal element 16 thereby releasing the fixation device.
[0138] FIG. 14 illustrates a released fixation device 14 in a closed position. As shown, the coupling member 19 remains separated from the shaft 12 of the interventional tool 10 and the proximal elements 16 are deployed so that tissue (not shown) may reside between the proximal elements 16 and distal elements 18 .
[0139] While the above described embodiments of the invention utilize a push-to-open, pull-to-close mechanism for opening and closing distal elements 18 , it should be understood that a pull-to-open, push-to-close mechanism is equally possible. For example, distal elements 18 may be coupled at their proximal ends to stud 74 rather than to coupling member 19 , and legs 68 may be coupled at their proximal ends to coupling member 19 rather than to stud 74 . In this example, when stud 74 is pushed distally relative to coupling member 19 , distal elements 18 would close, while pulling on stud 74 proximally toward coupling member 19 would open distal elements 18 .
[0140] In some situations, the valve leaflets may fully or partially detach from the fixation device due to poor leaflet insertion between the proximal and distal elements. Evaluation of valve leaflet insertion in the fixation device is therefore performed using standard imaging technology such as echocardiography and fluoroscopy. However, depending on the angle and/or position of the proximal and distal elements relative to the delivery catheter, it can be challenging to assess the depth of valve leaflet insertion into the fixation device, or to differentiate between the leaflets and the proximal and distal elements of the fixation device. Visualization is therefore preferably performed with the distal elements in a more open configuration with the distal elements displaced from one another. However, since many current embodiments of the fixation device only permit the proximal elements to open up to an included angle of about 85°, the distal elements therefore must be closed up to an included angle of between about 45° and preferably 60° in order securely grasp the valve leaflets between the proximal and distal elements. While this configuration helps an operator visualize and differentiate between the valve leaflets and the fixation device, it is preferable to further open up the distal elements to an included angle of greater than 90°, and more preferably to 120° or more. Thus, it would be desirable to modify the proximal elements to open up further.
[0141] FIGS. 15A-15H illustrate an embodiment of a fixation device similar to the device of FIGS. 7A-14 , with a major difference being that this embodiment includes a gripper pusher. FIG. 15A illustrates fixation device 14 that generally takes the same form as fixation device 14 previously described. In addition to the features previously described, fixation device 14 also includes a gripper pusher 81 . The gripper pusher 81 deflects radially outward resulting in a bowed region 83 that expands outward until the bowed region 83 engages a superior surface of the proximal elements 16 . As the bowed region 83 continues to deflect radially outward, it further pushes on the proximal elements 16 such that the proximal elements are deflected and rotated outward toward the engagement surface of the distal elements 18 . Thus, the proximal elements 16 may be deflected outward further than they normally would, and therefore the valve leaflets may be captured between the proximal and distal elements when the distal elements are disposed in a more open position with a larger included angle therebetween. In preferred embodiments, the included angle between the distal elements is greater than about 90°, preferably greater than about 110°, and more preferably greater than about 120°. In the embodiment of FIG. 15A , the gripper pusher 81 includes two arms formed from a metal, polymer or other wire-like material. Exemplary materials include cobalt chromium alloy, stainless steel, nitinol, and the like. Polymers may also be used to fabricate the gripper pusher. The gripper pusher 81 may be actuated to bow outwards upon application of an axially oriented compressive force that is generally parallel to the longitudinal axis of the gripper pusher arms. During compression, the gripper pusher bows outward forming bowed region 83 . In other embodiments, the gripper pusher may be a spring which is resiliently biased to bow outward forming bowed region 83 . However, when proximal element lines (not illustrated here) are tensioned to lift the proximal elements 16 , the gripper pusher springs will collapse to a reduced profile.
[0142] FIG. 15B illustrates the fixation device 14 having a covering for tissue ingrowth that is substantially the same as discussed in FIGS. 16A-16C below, and with the gripper pusher 81 expanded such that the proximal elements 16 (also referred to as gripping elements) are in engagement with the distal elements 18 (also referred to as fixation elements). The valve leaflets (not shown for convenience) are pinched therebetween. FIG. 15C illustrates the gripper pusher 81 in the collapsed configuration. The bowed region 83 collapses, allowing the proximal elements 16 to retract towards shaft 12 , allowing the valve leaflets (not shown) to be released from the fixation device 14 . The gripper pusher 83 is offset from the proximal elements 16 so that the proximal elements can retract without interfering with the gripper pusher 81 .
[0143] FIG. 15D highlights the gripper pusher 83 which preferably includes two spring arms 99 . Each arm 99 is formed from wire or machined from a sheet or other stock material and in this embodiment has a rectangular cross-section, although other cross-sections are also contemplated. A distal portion 91 of each arm 99 has a notched region 93 forming a pair of fingers that can engage with a boss or other attachment mechanism on the fixation device. The notch may be released from the boss when the fixation device 14 is detached from the delivery catheter shaft 12 . Additionally, each arm includes two bowed regions, or peaks, including a larger distal bowed region 83 , and a smaller proximal bowed region 95 . The larger bowed region 83 flares outwardly a greater distance so as to engage and push the proximal elements 16 into engagement with the distal elements 18 . When the distal bowed region 83 relaxes and collapses away from the proximal elements 16 , or when collapsed by retraction of the proximal elements, the smaller proximal bowed regions 95 expand radially outward. An attachment ring or coupling collar 97 is adjacent nose 318 (described in greater detail below) and is slidably disposed over the shaft 12 and allows coupling of the gripper arms 99 to the shaft 12 . FIG. 15E illustrates the distal bowed region 83 in engagement with the proximal elements 16 , and also illustrates engagement of the notch 93 on the distal portion of each arm 99 with a boss 94 on the fixation device 14 .
[0144] Additional components may be provided to facilitate maintaining the alignment of the gripper pushers 83 relative to the delivery catheter shaft 12 . FIG. 15 E 1 shows a cross-sectional view of the delivery catheter shaft 12 with the gripper pusher 83 and FIG. 15 E 2 shows a side view of the same. As shown in FIGS. 15 E 1 and 15 E 2 , each arm 99 may have a slot 8112 and the delivery catheter shaft 12 may have one or more protrusions 1281 which the slots 8112 straddle to maintain the alignment of the gripper pusher 83 relative to the delivery catheter shaft 12 . The region of the arm 99 having the slot 8112 is wider than the remainder of the arm 99 to accommodate the slot 8112 . The greater width may also allow the arm 99 to be pushed to the side without becoming misaligned relative to the delivery catheter shaft 12 . FIG. 15 E 3 shows a cross-sectional view of the delivery catheter shaft 12 and FIG. 15 E 4 shows a side view of the same. As shown in FIGS. 15 E 3 and 15 E 4 , each arm 99 may have one or more inwardly bowed regions 8212 and the delivery catheter shaft 12 may have one or more troughs 1282 which accommodate the inwardly bowed regions 8212 to maintain the alignment of the gripper pusher 83 relative to the delivery catheter shaft 12 .
[0145] FIG. 15F illustrates a top view of the gripper pusher 81 having two arms 99 . FIG. 15F illustrates that the two arms 99 are offset from one another such that in this exemplary embodiment, angle α is about 160° and angle θ is about 200°, as opposed to positioning the arms 180° apart from one another. Asymmetrically positioning the arms about the shaft creates a larger gap on one side, and allows the proximal elements 16 to avoid colliding with the gripper pusher arms 99 when the proximal elements retract against shaft 12 . FIG. 15G is a top view of collar 97 , and FIG. 15H is a side view of gripper pusher arm 99 . A cutout 98 on one side of arm 99 creates additional room between arms 99 , thereby also helping to prevent the proximal elements 16 from interfering with the gripper pusher 83 when the proximal elements 16 are retracted. The cutouts are on both arms 99 and face the larger gap represented by angle θ to maximize room for the proximal elements 16 .
[0146] As described above, for example, with reference to FIGS. 9A and 9B , actuation of the proximal elements 16 may be accomplished by using one or more proximal element lines or actuators 90 . Such actuation can be achieved in various ways. For example, as shown in FIG. 15I , the proximal element actuators 90 A and 90 B could be threaded through line loops 48 A and 48 B, which are disposed on the radially outward and proximal sides of the proximal elements 16 A and 16 B, respectively. The distal ends of proximal element actuators 90 A and 90 B may comprise closed loops 95 A and 95 B, which encircle the shaft 12 and the coupling member 19 shown in FIG. 15I as coupled together. As discussed above, the shaft 12 and the coupling member 19 can be releasably coupled together. To have the closed loops 95 A and 95 B surround shaft 12 and the coupling member 19 , the closed loops 95 A and 95 B are placed over the shaft 12 and/or the coupling member 19 prior to the coupling shaft 12 and the coupling member 19 together. When the closed loops 95 A and 95 B encircle the shaft 12 and the coupling member 19 , the closed loops 95 A and 95 B hold the distal ends of the proximal element actuators 90 A and 90 B in place relative to the shaft 12 and the coupling member 19 and restrict the degree to which the proximal element actuators 90 A and 90 B can be retracted. By being threaded through the line loops 48 A and 48 B, the proximal element actuators 90 A and 90 B are mechanically linked to the proximal elements 16 A and 16 B, respectively. Thus, as shown in FIG. 15J , when the proximal element actuators 90 A and 90 B are retracted proximally in a direction 96 , they move the proximal elements 16 A and 16 B away from the distal elements 18 A and 18 B, respectively. Similarly, pushing the proximal element actuators 90 A and 90 B distally moves the proximal elements 16 A and 16 B toward the distal elements 18 A and 18 B.
[0147] The proximal element actuators 90 A and 90 B may be moved so that the proximal elements 16 A and 16 B are moved at a variety of angles and distances from the distal elements 18 A and 18 B. And, the degree to which the proximal element actuators 90 A and 90 B are pushed or pulled can be maintained to keep the positions the proximal elements 16 A and 16 B have relative to the distal elements 18 . For example, as shown in FIG. 15K , the proximal element actuators 90 A and 90 B are pulled proximally and maintained in the position shown so as to maintain the proximal elements 16 A and 16 B in an intermediate position relative to the distal elements 18 . This intermediate position is between the position the proximal elements 16 A and 16 B are biased toward and that in which the proximal elements 16 A and 16 B are fully retracted as in FIG. 15J . As shown in FIG. 15N , once the proximal elements 16 A and 16 B are in a desired position, the shaft 12 and the coupling member 19 can be decoupled so that proximal retraction of the proximal element actuators 90 A and/or 90 B decouples the proximal element lines from the proximal elements 16 . Thus, the fixation device 14 can be left in place while the shaft 12 , the proximal element actuators 90 A and 90 B, and other parts can be removed from a site of operation. As shown in FIGS. 15O through 15O , the fixation device 14 typically includes a covering 100 substantially the same as discussed in FIGS. 16A-16C below.
[0148] It may be desirable to provide for independent actuation of the proximal elements 16 A and 16 B. For example, as shown in FIG. 15L , the proximal element actuator 90 A is proximally retracted and rotates the proximal element 16 A away from the distal element 18 A, while the proximal element actuator 90 B is pushed distally and rotates the proximal element 16 B toward the distal element 18 B. Similarly, as shown in FIG. 15M , the proximal element actuator 90 A is left alone, allowing the proximal element 16 A to maintain the position it is biased toward, while the proximal element actuator 90 B is proximally retracted, moving the proximal element 16 B away from the distal element 18 B. Providing for the independent actuation of the proximal elements 16 A and 16 B allows leaflets to be independently grasped by the proximal elements 16 A and 16 B and the distal elements 18 A and 18 B. Thus, the fixation device 14 can coapt leaflets more easily and at more optimal locations. For example, as opposed to grasping two leaflets simultaneously, a first leaflet can be grasped at a desired position and the fixation device 14 can then be repositioned so that a second leaflet can be grasped at a more optimal position. Alternatively, leaflets may be still be simultaneously grasped if desired as the independently actuatable proximal element actuators can still be moved simultaneously. Also, after leaflets are grasped, they can be released and the leaflets can be grasped again, for example, if the leaflets are malcoapted at the first grasp.
[0149] Embodiments of the fixation device similar to the devices described above may include both a gripper pusher 81 and independently actuatable proximal elements 16 A and 16 B, as shown for example in FIG. 15O . Having both a gripper pusher 81 and independently actuatable proximal elements 16 A and 16 B may allow the fixation device to have many of the advantages described above such as to more accurately and more strongly grasp leaflets.
[0150] FIG. 15P shows the distal end of a proximal element actuator 90 . The proximal element actuator 90 comprises a round section 90 R and a flat section 90 F distal of the round section 90 R. When this proximal element actuator 90 is threaded through a proximal element 16 and coupled to a fixation device 14 , the flatter portion of the flat section may be positioned so that it faces proximal element 16 . As the proximal element actuator 90 is proximally advanced, it will therefore tend to deflect it in the direction toward the proximal element 16 instead of in other directions and push the proximal element. The proximal element actuator 90 further comprises a looped end 95 . As shown in FIG. 15P , the looped end 95 may comprise a separate loop of wire attached with the distal end of the flat section 90 F at its distal end, for example, with solder 94 .
[0151] The proximal element actuator 90 may also be releasably coupled to the fixation device 14 in other ways. For example, as shown in FIGS. 15Q and 15R , the proximal element actuator 90 comprises a spiraled distal section 95 L which is releasably coupled to the fixation device 14 . The spiraled distal section 95 L is wrapped about the shaft 12 and/or the coupling mechanism 19 . Retracting the proximal element actuator 90 with sufficient force may deform the spiraled distal section 95 L so that it is released from the fixation device 14 . Alternatively or in combination, the spiraled distal section 95 L may comprise a shape memory material such that the spiraled distal section 95 L is straightened upon the application of a sufficient amount of heat, facilitating the proximal retraction of the proximal element actuator 90 away from the fixation device 14 .
[0152] The proximal element actuator 90 may be releasably coupled to the fixation device 14 by suture. As shown in FIGS. 15S and 15T , a proximal element actuator 90 is releasably coupled to the fixation device 14 via a suture knot 95 S. Each proximal actuator 90 may be coupled to the fixation device 14 by a separate suture knot 95 S. Alternatively, a pair of proximal actuators 90 may be coupled to the fixation device 14 by a single suture knot.
[0153] A proximal element actuator 90 may comprise an enlarged section 90 T as shown in FIGS. 15U and 15V . The diameter of the enlarged section 90 T exceeds the diameter of the opening of the loop line 48 . As the proximal element actuator 90 is retracted, the loop line 48 restricts the proximal movement of the enlarged section 90 T. Thus, a pulling force is exerted on the loop line 48 and proximal element 16 , which facilitates the actuation of a proximal element 16 . The enlarged section 90 T may be a sleeve attached over the proximal element actuator 90 .
[0154] The proximal element actuator 90 may be releasably coupled to the proximal element 16 at the radially outward ends of the proximal element 16 by an attachment device, for example, as shown in FIGS. 15 W 1 to 15 W 2 . The attachment device may comprise a ring 90 CR as shown in a perspective view in FIG. 15W 1 , a short clip 90 CC as shown in a perspective view in FIG. 15 W 2 , or a long clip 90 CL as shown in FIGS. 15 W 3 to FIG. 15 W 5 . FIG. 15 W 3 shows a perspective view of the long clip 90 CL attaching the proximal element actuator 90 to a proximal element 16 . FIGS. 15 W 4 and 15 W 5 show a front and side view of the same, respectively. The long clip 90 CL may comprise a pair of legs 90 CLL which traverse the length of the proximal element 16 . As shown in FIG. 15 W 5 , a leg 90 CLL is disposed between two rows of barbs 60 .
[0155] The above described attachment devices may be spring loaded to latch onto or sized to slip fit into the radially outward ends of the proximal element 16 . As the proximal element actuator 90 is retracted, the attachment device continues to be attached to the proximal element 16 . As the proximal element 16 is rotated to be substantially parallel to a shaft 19 , however, further proximal retraction of the proximal element actuator 90 can release the attachment device from the outer end of the proximal element 16 . A mechanical mechanism may be provided to limit the degree to which the proximal element actuator 90 can be proximally retracted so that the attachment device is not detached inadvertently. Instead, detachment will occur only upon retraction of the whole delivery device, including the proximal element actuators 90 , from the fixation device 14 .
[0156] The proximal element actuator 90 may comprise two lines: an actuation line 90 AA and a release line 90 RR, for example, as shown in FIGS. 15 X 1 to 15 X 3 . FIG. 15 X 1 shows a perspective view of an radially outer end of a proximal element 16 having an aperture 48 A. FIG. 15 X 2 shows a cross-sectional view of the same. The actuation line 90 AA has a looped end 90 AAL which is threaded through the aperture 48 A to cross through proximal element 16 . The release line 90 RR is threaded through the portion of the looped end 90 AAL. In FIG. 15 X 3 , the actuation line 90 AA and the release line 90 RR are similarly positioned through loop line 48 of proximal element 16 . While the actuation line 90 AA and the release line 90 RR are positioned in the arrangement shown in FIGS. 15 X 1 to 15 X 3 , retracting the actuation line 90 AA rotates the proximal element 16 relative to a distal element 18 similarly to the embodiments described above. Retracting the release line 90 RR so that it no longer is threaded through the looped end 90 AAL allows the actuation line to be retracted away from the proximal element 16 .
[0157] In many embodiments, the shaft 12 and the coupling member 19 are releasably coupled together via an L-locking mechanism. For example, as shown in FIG. 15 Y 1 , the proximal element actuator 90 may comprise a round T-shaped end 90 T distal of the flat section 90 F and the shaft 12 may comprise L-shaped ends 12 L. As shown in the perspective view of FIG. 15 Y 2 , the proximal element actuator 90 is releasably coupled to the coupling member 19 when it and shaft 12 are placed into the channel 19 C of the coupling member 19 . As the shaft 12 is placed through the channel 19 C, the L-shaped ends 12 L are forced inwardly until they reach apertures 19 A. At that point, the L-shaped ends 12 L expand outwardly to fit into the apertures 19 A, thereby locking the shaft 12 in place relative to the coupling member 19 , as shown in cross-sectional view of FIG. 15 Y 3 . The round T-shaped distal end 90 T will typically be placed in the channel 19 C prior to the shaft 12 . As shown in FIG. 15 Y 3 , the round T-shaped distal end 90 T then becomes trapped in the space 19 CA between the channel 19 C and a wider portion of the shaft 12 when the shaft is placed therein. Other L-locking or other locking mechanisms are described in commonly assigned U.S. patent application Ser. No. 12/393,452 entitled “Detachment Mechanism for Implantable Fixation Devices” and filed Feb. 26, 2009, the full contents of which are incorporated herein by reference.
[0158] The round T-shaped end 90 T of the proximal element actuator 90 may also be used to facilitate releasably coupling the proximal element line 90 to the shaft 12 and coupling member 19 is many other ways. For example, as shown in FIG. 15 Z 1 , the L-shaped end 12 L of the shaft 12 may comprise at least one proximal element line slot 12 S. As shown in FIGS. 15 Z 3 and 15 Z 4 , the T-shape end 90 T of the proximal element actuator 90 is slid into the proximal element line slot 12 L. Then, the shaft 12 is placed into the coupling member 19 , thereby also locking the proximal element line 90 in place. As shown in FIG. 15 Z 5 , removing the shaft 12 from the coupling member 19 allows the proximal element line 90 to be slid out of the proximal element line slot 12 S of L-shaped end 12 L, thereby decoupling the proximal element actuator 90 from both the shaft 12 and the coupling device 19 .
[0159] As shown in FIG. 15 AA 1 , the proximal element actuator 90 may comprise a flat T-shaped end 90 TF. The shaft 12 may further comprise an inner distal covering 1511 surrounding a distal portion of the shaft 12 and an outer distal covering 1521 surrounding the inner distal covering. The inner distal covering 1511 will typically be in a fixed position relative to the shaft 12 while the outer distal covering will be moveable relative to the shaft 12 at a range determined by tabs 1515 of inner distal covering 1511 placed through side channels 1525 of the outer distal covering 1521 . To releasably couple the proximal element actuator 90 to the shaft 12 and coupling line 19 , the T-shaped end 90 TF is fit into a T-shaped cutout 1513 of inner distal covering 1511 , and when the shaft 12 is placed into the coupling device 19 , the coupling device 19 pushes the outer distal covering 1521 over the inner distal covering 1511 to cover the T-shaped cutout 1513 as well as the T-shaped end 90 TF, as shown in FIG. 15 AA 2 . In some embodiments, the outer distal covering 1521 may be spring loaded against the inner distal cover 1523 so that tend to maintain their relative positions shown in FIG. 15 AA 1 .
[0160] Proximal element actuators 90 may be releasably coupled to the fixation device 14 in a variety of ways using variations of inner and outer distal collars over the distal portion of shaft 12 , for example, as shown in FIGS. 15 AB 1 to 15 AB 7 . FIG. 15 AB 1 shows an inner distal collar 1511 A having a pair of T-shaped cutouts 1513 and a tab 1514 . FIG. 15 AB 3 shows an outer distal collar 1521 A having a channel 1524 . The channel 1524 guides the inner distal collar 1511 A via its tab 1514 as the inner distal collar 1511 A is slid into the outer distal collar 1521 A, for example as shown in FIGS. 15 AB 3 through 15 AB 5 . As in the embodiment shown in FIGS. 15 AA 1 and 15 AA 2 , to releasably couple the proximal element actuators 90 to the shaft 12 and coupling member 19 , the T-shaped end 90 TF is fit into a T-shaped cutout 1513 of inner distal collar 1511 S. When the shaft 12 is placed into the coupling device 19 , the coupling member 19 pushes the outer distal collar 1521 S over the inner distal collar 1511 S to cover the T-shaped cutout 1513 as well as the T-shaped end 90 TF, as shown in FIGS. 15 AB 6 and 15 AB 7 .
[0161] As described below, a delivery device or delivery catheter 300 may be used to introduce and position fixation devices as described above. In embodiments of the invention with independently actuatable proximal element lines, the handle 304 of the delivery catheter will typically include control mechanisms for the independently actuable proximal element lines. For example, a control mechanism may comprise a pair of independently actuable proximal element line handles 393 A and 393 B placed in parallel, as shown in FIG. 15 AC 1 , or placed coaxially, as shown in FIG. 15 AC 2 . The proximal element line handles 393 A and 393 B are coupled to proximal element lines 90 A and 90 B and may share a common or interconnecting lumens in the delivery device. Stop may be provided to limit the degree to which the proximal element line handles 393 A and 393 B can be retracted or advanced, thereby limiting the degree to which the proximal element actuators 90 A and 90 B can be retracted or advanced. In some embodiments, for example, as shown by FIGS. 15 AC 3 and 15 AC 4 , a proximal element line handle 393 may be actuated by a rotatable switch 395 attached to it.
[0162] B. Covering on Fixation Device
[0163] The fixation device 14 may optionally include a covering. The covering may assist in grasping the tissue and may later provide a surface for tissue ingrowth. Ingrowth of the surrounding tissues, such as the valve leaflets, provides stability to the device 14 as it is further anchored in place and may cover the device with native tissue thus reducing the possibility of immunologic reactions. The covering may be comprised of any biocompatible material, such as polyethylene terepthalate, polyester, cotton, polyurethane, expanded polytetrafluoroethylene (ePTFE), silicon, or various polymers or fibers and have any suitable form, such as a fabric, mesh, textured weave, felt, looped or porous structure. Generally, the covering has a low profile so as not to interfere with delivery through an introducer sheath or with grasping and coapting of leaflets or tissue.
[0164] FIGS. 16A-16C illustrate a covering 100 on the fixation device 14 wherein the device 14 is in various positions. FIG. 16A shows the covering 100 encapsulating the distal elements 18 and the actuation mechanism 58 while the device 14 is in the open position. Thus, the engagement surfaces 50 are covered by the covering 100 which helps to minimize trauma on tissues and provides additional friction to assist in grasping and retaining tissues. FIG. 16B shows the device 14 of FIG. 16A in the inverted position. The covering 100 is loosely fitted and/or is flexible or elastic such that the device 14 can freely move to various positions and the covering 100 conforms to the contours of the device 14 and remains securely attached in all positions. FIG. 16C shows the device 14 in the closed position. Thus, when the fixation device 14 is left behind as an implant in the closed position, the exposed surfaces of the device 14 are substantially covered by the covering 100 . It may be appreciated that the covering 100 may cover specific parts of the fixation device 14 while leaving other parts exposed. For example, the covering 100 may comprise sleeves that fit over the distal elements 18 and not the actuation mechanism 58 , caps that fit over the distal ends 54 of the distal elements 18 or pads that cover the engagement surfaces 50 , to name a few. It may be appreciated that, the covering 100 may allow any frictional accessories, such as barbs, to be exposed. Also, the covering 100 may cover the proximal elements 16 and/or any other surfaces of the fixation device 14 . In any case, the covering 100 should be durable to withstand multiple introduction cycles and, when implanted within a heart, a lifetime of cardiac cycles.
[0165] The covering 100 may alternatively be comprised of a polymer or other suitable materials dipped, sprayed, coated or otherwise adhered to the surfaces of the fixation device 14 . Optionally, the polymer coating may include pores or contours to assist in grasping the tissue and/or to promote tissue ingrowth.
[0166] Any of the coverings 100 may optionally include drugs, antibiotics, anti-thrombosis agents, or anti-platelet agents such as heparin, COUMADIN® (Warfarin Sodium), to name a few. These agents may, for example, be impregnated in or coated on the coverings 100 . These agents may then be delivered to the grasped tissues surrounding tissues and/or bloodstream for therapeutic effects.
[0167] C. Fixation Device Locking Mechanisms
[0168] As mentioned previously, the fixation device 14 optionally includes a locking mechanism for locking the device 14 in a particular position, such as an open, closed or inverted position or any position therebetween. It may be appreciated that the locking mechanism includes an unlocking mechanism which allows the device to be both locked and unlocked. FIGS. 17-20 illustrate an embodiment of a locking mechanism 106 . Referring to FIG. 17 , in this embodiment, the locking mechanism 106 is disposed between the coupling member 19 and the base 69 of the actuation mechanism 58 . The base 69 is fixedly attached to the stud 74 which extends through the locking mechanism 106 . The stud 74 is releasably attached to the actuator rod 64 which passes through the coupling member 19 and the shaft 12 of the interventional tool 10 . The base 69 is also connected to the legs 68 of the actuation mechanism 58 which are in turn connected to the distal elements 18 .
[0169] FIG. 17 also illustrates the proximal elements 16 , which in this embodiment straddle the locking mechanism and join beneath the locking mechanism 106 . The proximal elements 16 are shown supported by proximal element lines 90 . The proximal elements 16 are raised and lowered by manipulation of the proximal element lines 90 . In addition, lock lines 92 are shown connected with a release harness 108 of the locking mechanism 106 . The lock lines 92 are used to lock and unlock the locking mechanism 106 as will be described below. The proximal element lines 90 and lock lines 92 may be comprised of any suitable material, typically wire, nitinol wire, cable, suture or thread, to name a few. In addition, the proximal element lines 90 and/or lock lines 92 may include a coating, such as parylene. Parylene is a vapor deposited pinhole free protective film which is conformal and biocompatible. It is inert and protects against moisture, chemicals, and electrical charge.
[0170] FIG. 18 provides a front view of the locking mechanism 106 of FIG. 17 . However, here the proximal elements 16 are supported by a single proximal element line 90 which is through both of the proximal elements 16 . In this arrangement both of the elements are raised and lowered simultaneously by action of a single proximal element line 90 . Whether the proximal elements 16 are manipulated individually by separate proximal element lines 90 or jointly by a single proximal element line 90 , the proximal element lines 90 may extend directly through openings in the proximal elements and/or through a layer or portion of a covering 100 on the proximal elements, or through a suture loop above or below a covering 100 .
[0171] FIGS. 19-20 illustrate the locking mechanism 106 showing the locking mechanism 106 in the unlocked and locked positions respectively. Referring to FIG. 19 , the locking mechanism 106 includes one or more wedging elements, such as rolling elements. In this embodiment, the rolling elements comprise a pair of barbells 110 disposed on opposite sides of the stud 74 , each barbell having a pair of generally cylindrical caps and a shaft therebetween. The barbells 110 and the stud 74 are preferably comprised of cobalt chromium or stainless steel, however any suitable material may be used. The barbells 110 are manipulated by hooked ends 112 of the release harness 108 . When an upwards force is applied to the harness 108 by the lock line 92 (illustrated in FIG. 17 ), the hooked ends 112 raise the barbells 110 against a spring 114 , as shown in FIG. 19 . This draws the barbells 110 up along a sidewall or sloping surface 116 which unwedges the barbells 110 from against the stud 74 . In this position, the stud 74 is free to move. Thus, when the lock line 92 raises or lifts the harness 108 , the locking mechanism 106 is in an unlocked position wherein the stud 74 is free to move the actuation mechanism 58 and therefore the distal elements 18 to any desired position. Release of the harness 108 by the lock line 92 transitions the locking mechanism 106 to a locked position, illustrated in FIG. 20 . By releasing the upwards force on the barbells 110 by the hooked ends 112 , the spring 114 forces the barbells 110 downwards and wedges the barbells 110 between the sloping surface 116 and the stud 74 . This restricts motion of the stud 74 , which in turn locks the actuation mechanism 58 and therefore distal elements 18 in place. In addition, the stud 74 may include one or more grooves 82 or indentations which receive the barbells 110 . This may provide more rapid and positive locking by causing the barbells 110 to settle in a definite position, increase the stability of the locking feature by further preventing movement of the barbells 110 , as well as tangible indication to the user that the barbell has reached a locking position. In addition, the grooves 82 may be used to indicate the relative position of the distal elements 18 , particularly the distance between the distal elements 18 . For example, each groove 82 may be positioned to correspond with a 0.5 or 1.0 mm decrease in distance between the distal elements 18 . As the stud 74 is moved, the barbells 110 will contact the grooves 82 ; by counting the number of grooves 82 that are felt as the stud 74 is moved, the user can determine the distance between the distal elements 18 and can provide the desired degree of coaptation based upon leaflet thickness, geometry, spacing, blood flow dynamics and other factors. Thus, the grooves 82 may provide tactile feedback to the user.
[0172] The locking mechanism 106 allows the fixation device 14 to remain in an unlocked position when attached to the interventional tool 10 during grasping and repositioning and then maintain a locked position when left behind as an implant. It may be appreciated, however, that the locking mechanism 106 may be repeatedly locked and unlocked throughout the placement of the fixation device 14 if desired. Once the final placement is determined, the lock line 92 and proximal element lines 90 are removed and the fixation device is left behind.
[0173] FIGS. 21 , 22 A- 22 B illustrate another embodiment of a locking mechanism 106 . Referring to FIG. 21 , in this embodiment, the locking mechanism 106 is again disposed between the coupling member 19 and the base 69 of the actuation mechanism 58 . The base 69 is connected to the stud 74 which extends through the locking mechanism 106 , and connects to an actuator rod which extends through the coupling member 19 and the shaft 12 of the interventional tool 10 . The base 69 is also connected to the legs 68 of the actuation mechanism 58 which are in turn connected to the distal elements 18 . FIG. 21 also illustrates the proximal elements 16 which manipulate the locking mechanism 106 in this embodiment. The locking mechanism 106 comprises folded leaf structures 124 having overlapping portions 124 a , 124 b , each folded structure 124 being attached to a proximal element 16 . In FIG. 21 and FIG. 22A , the folded structures 124 are shown without the remainder of the locking mechanism 106 for clarity. Proximal elements 16 are flexible and resilient and are biased outwardly. The folded leaf structures 124 include holes 125 ( FIG. 22B ) in each overlapping portion 124 a , 124 b so that the stud 74 passes through the holes 125 of the portions 124 a , 124 b as shown. The locking mechanism includes slots into which ends 123 of the folded leaf structures 124 are fixed. When the proximal elements 16 are in an undeployed position, as in FIG. 21 , the folded leaf structures 124 lie substantially perpendicular to the stud 74 so that the holes 125 in each overlapping portion are vertically aligned. This allows the stud 74 to pass freely through the holes and the locking mechanism 106 is considered to be in an unlocked position.
[0174] Deployment of the proximal elements 16 , as shown in FIG. 22A , tilts the folded leaf structures 124 so as to be disposed in a non-perpendicular orientation relative to the stud 74 and the holes 125 are no longer vertically aligned with one another. In this arrangement, the stud 74 is not free to move due to friction against the holes of the folded leaf structure 124 . FIG. 22B provides a larger perspective view of the folded structures 124 in this position. Thus, the locking mechanism 106 is considered to be in a locked position. This arrangement allows the fixation device 14 to maintain an unlocked position during grasping and repositioning and then maintain a locked position when the proximal elements 16 are deployed and the fixation device 14 is left behind as an implant. It may be appreciated, however, that the locking mechanism 106 may be repeatedly locked and unlocked throughout the placement of the fixation device 14 if desired.
[0175] FIGS. 23 , 24 A- 24 B illustrate another embodiment of a locking mechanism 106 . Referring to FIG. 22 , in this embodiment, the locking mechanism 106 is again disposed between the coupling member 19 and the base 69 of the actuation mechanism 58 . And, the base 69 is connected to the stud 74 which extends through the locking mechanism 106 and connects to an actuator rod which extends through the coupling member 19 and the shaft of the interventional tool 10 . FIG. 22 illustrates the proximal elements 16 which manipulate the locking mechanism 106 in this embodiment. The locking mechanism 106 comprises C-shaped structures 128 , each C-shaped structure 128 attached to a proximal element 16 . The C-shaped structures 128 hook around the stud 74 so that the stud 74 passes through the “C” of each structure 128 as shown in FIGS. 24A-24B . As shown, the structures 128 cross each other and the “C” of each structure 128 faces each other. A spring 130 biases the C-shaped structures into engagement with one another. When the proximal elements are in an undeployed position, as in FIG. 24A , the C-shaped structures 128 are urged into an orientation more orthogonal to the axial direction defined by stud 74 , thus bringing the “C” of each structure 128 into closer axial alignment. This allows the stud 74 to pass freely through the “C” of each structure 128 . Deployment of the proximal elements 16 outwardly urges the C-shaped structures into a more angular, non-orthogonal orientation relative to stud 74 causing the sidewalls of the “C” of each structure 128 to engage stud 74 more forcefully. In this arrangement, the stud 74 is not free to move due to friction against the “C” shaped structures 128 .
[0176] D. Additional Embodiments of Fixation Devices
[0177] In other embodiments, the proximal elements may be manipulated to enhance gripping. For example, the proximal elements may be lowered to grasp leaflets or tissue between the proximal and distal elements, and then the proximal elements may be moved to drag the leaflets or tissue into the fixation device. In another example, the proximal elements may be independently lowered to grasp the leaflets or tissue. This may be useful for sequential grasping. In sequential grasping, one proximal element is lowered to capture a leaflet or tissue portion between the proximal and distal elements. The fixation device is then moved, adjusted or maneuvered to a position for grasping another leaflet or tissue portion between another set of proximal and distal elements. In this position, the second proximal element is then lowered to grasp this other leaflet or tissue portion.
[0178] Other exemplary embodiments of fixation devices are disclosed in U.S. Pat. No. 7,563,267 (Attorney Docket No. 020489-001400US) and U.S. Pat. No. 7,226,467 (Attorney Docket No. 020489-001700US), the entire contents of each, fully incorporated herein by reference. One of skill in the art will appreciate that the various features of the disclosed fixation devices may be substituted with one another or used in combination with other disclosed features.
IV. Delivery Device
[0179] A. Overview of Delivery Device
[0180] FIG. 25 provides a perspective view of an embodiment of a delivery device or delivery catheter 300 which may be used to introduce and position a fixation device as described above. The delivery catheter 300 includes a shaft 302 , having a proximal end 322 and a distal end 324 , and a handle 304 attached to the proximal end 322 . A fixation device (not shown) is removably coupleable to the distal end 324 for delivery to a site within the body, typically for endovascular delivery to the mitral valve. Thus, extending from the distal end 324 is a coupling structure 320 for coupling with a fixation device. Also extending from the distal end 324 is an actuator rod 64 . The actuator rod 64 is connectable with the fixation device and acts to manipulate the fixation device, typically opening and closing the distal elements. Such coupling to a fixation device is illustrated in FIG. 26 .
[0181] FIG. 26 illustrates an embodiment of a fixation device 14 coupled to the distal end 324 of the delivery catheter 300 . The shaft 302 is shown having a nose 318 near its distal end 324 . In this embodiment, the nose 318 has a flanged shape. Such a flanged shape prevents the nose 318 from being retracted into a guiding catheter or introducer as will be discussed in later sections. However, it may be appreciated that the nose 318 may have any shape including bullet, rounded, blunt or pointed, to name a few. Extending from the nose 318 is a compression coil 326 through which the coupling structure 320 and actuator rod 64 pass. The actuator rod 64 is coupleable, as shown, with the stud 74 of the fixation device 14 . Such coupling is illustrated in FIG. 27 .
[0182] FIG. 27 illustrates a portion of the shaft 302 of the delivery catheter 300 and a fixation device 14 which is coupleable with the catheter 300 . Passing through the shaft 302 is the actuator rod 64 . In this embodiment, the actuator rod 64 comprises a proximal extremity 303 and a distal extremity 328 , the distal extremity 328 of which is surrounded by a coil 330 . The proximal extremity 303 is typically comprised of stainless steel, nitinol, or Elgiloy®, to name a few, and may have a diameter in the range of 0.010 in. to 0.040 in., preferably 0.020 in. to 0.030 in., more preferably 0.025 in., and a length in the range of 48 to 72 in. The distal extremity 328 may be tapered, is typically comprised of stainless steel, nitinol, or Elgiloy®, to name a few, and may have a diameter in the range of 0.011 to 0.025 in and a length in the range of 4 to 12 in. Such narrowing increases flexibility of the distal end 324 of the actuator rod 64 . The actuator rod 64 further comprises a joiner 332 which is attached to the distal extremity 328 . The joiner 332 is removably attachable with stud 74 of the fixation device 14 . In this embodiment, the joiner 332 has internal threads which mate with external threads on the stud 74 of the fixation device 14 . As described previously, the stud 74 is connected with the distal elements 18 so that advancement and retraction of the stud 74 , by means of the actuator rod 64 , manipulates the distal elements. Likewise, the coupling member 19 of the fixation device 14 mates with the coupling structure 320 of the catheter 300 . Thus, the coupling member 19 and coupling structure 320 function as previously described in relation to FIGS. 6A-6B .
[0183] Referring back to FIG. 26 , the fixation device 14 may also include a locking mechanism which includes a release harness 108 , as previously described in relation to FIGS. 17-20 . Lock lines 92 are connected with the release harness 108 to lock and unlock the locking mechanism 106 as previously described. The lock lines 92 extend through the shaft 302 of the delivery catheter 300 and may connect with the release harness 108 in various arrangements as will be illustrated in later sections. Similarly, proximal element lines 90 extend through the shaft 302 of the delivery catheter 300 and connect with the proximal elements 16 . The proximal elements 16 are raised and lowered by manipulation of the proximal element lines 90 as previously described. The proximal element lines 90 may connect with the proximal elements 16 in various arrangements as will be illustrated in later sections.
[0184] Referring back to FIG. 25 , the handle 304 attached to the proximal end 322 of the shaft 302 is used to manipulate the coupled fixation device 14 and to optionally decouple the fixation device 14 for permanent implantation. As described, the fixation device 14 is primarily manipulated by the actuator rod 64 , proximal element lines 90 and lock lines 92 . The actuator rod 64 manipulates the distal elements 18 , the proximal element lines 90 manipulate the proximal elements 16 and the lock lines 92 manipulate the locking mechanism. In this embodiment, the actuator rod 64 may be translated (extended or retracted) to manipulate the distal elements 18 . This is achieved with the use of the actuator rod control 314 which will be described in later sections. The actuator rod 64 may also be rotated to engage or disengage the threaded joiner with the threaded stud 74 . This is achieved with the use of the actuator rod handle 316 which will also be described in later sections. Further, the proximal element lines 90 may be extended, retracted, loaded with various amounts of tension or removed with the use of the proximal element line handle 312 . And, the lock lines 92 may be may be extended, retracted, loaded with various amounts of tension or removed with the use of the lock line handle 310 . Both of these handles 310 , 312 will be described in more detail in later sections. The actuator rod handle 316 , actuator rod control 314 , proximal element line handle 312 and lock line handle 310 are all joined with a main body 308 within which the actuator rod 64 , proximal element lines 90 and lock lines 92 are guided into the shaft 302 . The handle 304 further includes a support base 306 connected with the main body 308 . The main body 308 is slideable along the support base 306 to provide translation of the shaft 302 . Further, the main body 308 is rotateable around the support base 306 to rotate the shaft.
[0185] While the embodiment of FIG. 27 is promising, in certain situations, the actuator rod 64 may deform, especially along the thinner distal extremity region 328 , during delivery of fixation device 14 , thereby making it more challenging to properly deliver and attach the fixation device to the valve leaflets. For example, when tracking tortuous vessels, or when steering the distal portion of the delivery device through large angles, e.g. 90° or more, the distal tapered extremity 328 of the actuator rod 64 may take a permanent set and thus may fail to return to a substantially straight configuration after being deflected. FIGS. 28A-28B illustrate an alternative embodiment of the actuator rod illustrated in FIG. 27 . In this embodiment, the distal tapered extremity 328 has been replaced with a flexible cable. Actuator rod 64 a is a long shaft or mandrel that generally takes the same form as actuator rod 64 in FIG. 27 . A flexible cable 2702 is disposed between a distal end of the actuator rod 64 a , and a proximal end of coupler or joiner 2708 . The flexible cable 2702 allows torque, tension, and compression to be transmitted to the coupler 2708 , while allowing bending and flexing without resulting in the flexible cable taking a set. In this exemplary embodiment, a distal portion of actuator rod 64 a is joined to a proximal end of the flexible cable 2702 with a sleeve 2704 . The sleeve 2704 has a central channel 2718 extending therethrough for receiving the flexible cable and the actuator rod. The sleeve 2704 may then be crimped, swaged, or otherwise reduced in diameter in order to fixedly attach the two ends together. In alternative embodiments, adhesives, welds, soldering joints, etc. may also be used to join the two ends together. Similarly, a proximal end of the coupler 2708 may include a central channel 2718 that is sized to receive a distal portion of the flexible cable 2702 . In this exemplary embodiment, the coupler is cylindrically shaped with a proximal portion 2716 having a larger diameter than the distal portion 2710 . After the proximal portion 2716 has been crimped or swaged onto the flexible cable, the diameters of the proximal and distal portions of the coupler may be the same, as illustrated in FIG. 28B . The distal portion of the coupler may include a threaded channel 2712 which may be threadably attached to the fixation device 14 , such as previously described above in FIGS. 7 and 27 . FIG. 28B illustrates the actuator rod 64 a after it has been coupled with the flexible cable and the coupler by swaging.
[0186] The flexible cable is preferably resiliently biased to return to a substantially straight or linear configuration, even after being bent or deflected by 90° or more. In preferred embodiments, the flexible cable is 25 cm or shorter, preferably 10 cm to 20 cm long, and more preferably 15 to 20 cm long. The flexible cable also has an outer diameter preferably 0.015″ to 0.035″ and more preferably is 0.020″ to 0.030″ and nominally is 0.025″ although one of skill in the art will appreciate that other dimensions may also be used. The actuator rod 64 a generally takes the same form as actuator rod 64 in FIG. 27 . The actuator rod 64 a and flexible cable 2702 are configured to transmit at least 0.74 inch-ounces of torque with a substantially 1:1 torque transmission ratio from the proximal end of the actuator mandrel to the distal end of the flexible cable. This torque is required to threadably disengage the coupler 2708 from the fixation device after the valve has been satisfactorily repaired. Additionally, the actuator rod 64 a and the flexible cable 2702 are also designed to transmit at least 2.5 pounds of compressive force distally to the fixation device in order to actuate the distal elements thereof. Also, the actuator rod and flexible cable can withstand at least 14.7 pounds of tensile force without substantial stretching or elongation. This force is experienced when actuating the fixation device to close the distal elements. Various metals, polymers, and other materials may be used for the actuator rod, flexible cable, sleeve, and coupler. However, in preferred embodiments, the coupler is fabricated from 17-4 H1150 stainless steel, while the cable comprises 304V stainless steel, and the mandrel is 304 stainless steel with an ultraspring wire temper.
[0187] Various configurations of the flexible cable may be used, such as the cable illustrated in FIGS. 29A-32B . The flexible cable of FIG. 29A-32B is a stranded cable with a reverse wind designed to have a high torque transmission ratio in the counterclockwise direction. This cable includes four layers of wires. The innermost layer 2802 is seen in FIG. 29A and includes three wires 2802 a , 2802 b , 2802 c helically wound together. FIG. 29B illustrates a cross-section of cable 2802 taken along the line A-A. The next layer 2902 comprises nine additional strands of wire 2904 wrapped around the innermost layer 2802 as illustrated in FIG. 30A . FIG. 30B is a cross-section taken along the line B-B. The next layer 3002 is illustrated in FIG. 31A , and comprises ten additional strands of wire 3006 wrapped around layer 2902 , and a cross-section taken along line D-D is shown in FIG. 31B . Finally, the outermost layer 3102 comprises ten more wires 3108 wrapped around layer 3002 as seen in FIG. 32A , with cross-sectional taken along line D-D in FIG. 32B . One of skill in the art will appreciate the various strand material characteristics (e.g. diameter, tensile strength, etc.) and winding patterns that may be used.
[0188] An alternative embodiment is illustrated in FIGS. 33A-37B . This embodiment is similar to that previously described above, with the major difference being that after the cable has been wound, it is drawn thereby altering the surface finish and some of the mechanical characteristics. FIG. 33A illustrates the innermost layer 3202 which includes three wires 3204 wound together, as seen in the cross-section of FIG. 33B taken along the line A-A. FIG. 34A shows the next layer 3302 which includes nine wires 3304 wrapped around the innermost layer 3202 . FIG. 34B shows a cross-section taken along line B-B. The next layer 3402 of wires are shown in FIG. 35A having ten wires 3404 wrapped around the previous layer 3302 , as illustrated in the cross-section of FIG. 35B taken along line C-C. The outermost layer 3502 is shown in FIG. 36A and includes another ten wires 3504 wrapped around the previous layer 3402 , with cross-section taken along line D-D in FIG. 36B . The assembly of four layers of wire are then drawn in order to alter the surface finish of the cable and to alter material properties of the finished cable assembly to a desired value. FIG. 37A illustrates the finished cable assembly 3602 with cross-section taken along line E-E in FIG. 37B . One of skill in the art will appreciate that other cable configurations may be used, and that these are only exemplary embodiments.
[0189] B. Delivery Catheter Shaft
[0190] FIG. 38 illustrates a cross-sectional view of the delivery catheter shaft 302 of FIG. 25 . In this embodiment, the shaft 302 has a tubular shape with inner lumen 348 and is comprised of a material which provides hoop strength while maintaining flexibility and kink resistance, such as a braided laminated material. Such material may include stainless steel braided or coiled wire embedded in a polymer such as polyurethane, polyester, Pebax, Grilamid TR55, and AESNO to name a few. To provide further support and hoop strength, a support coil 346 is disposed within the lumen 348 of shaft 302 as illustrated in FIG. 38 .
[0191] Passing through the support coil 346 are a variety of elongated bodies, including tubular guides and cylindrical rods. For example, one type of tubular guide is a compression coil 326 extending through lumen 348 from the proximal end 322 to the distal end 324 of the shaft 302 , and the actuator rod 64 extends through the compression coil 326 . Therefore, the compression coil typically has a length in the range of 48 to 60 in. and an inner diameter in the range of 0.020 to 0.035 in. to allow passage of the actuator rod 64 therethrough. The actuator rod 64 is manipulable to rotate and translate within and relative to the compression coil 326 . The compression coil 326 allows lateral flexibility of the actuator rod 64 and therefore the shaft 302 while resisting buckling and providing column strength under compression. The compression coil may be comprised of 304V stainless steel to provide these properties.
[0192] To provide additional tensile strength for the shaft 302 and to minimize elongation, a tension cable 344 may also pass through the support coil 346 . The tension cable 344 extends through lumen 348 from the proximal end 322 to the distal end 324 of the shaft 302 . Therefore, the tension cable 344 typically has a diameter in the range of 0.005 in. to 0.010 in. and a length in the range of 48 to 60 in. In preferred embodiments, the tension cable 344 is comprised of 304V stainless steel.
[0193] In addition, at least one lock line shaft 341 having a tubular shape may be present having a lock line lumen 340 through which lock lines 92 pass between the lock line handle 310 and the locking mechanism 106 . The lock line shaft 341 extends through lumen 348 from the proximal end 322 to the distal end 324 of the shaft 302 . Therefore, the lock line shaft 341 typically has a length in the range of 48 to 60 in., an inner diameter in the range of 0.016 to 0.030 in., and an outer diameter in the range of 0.018 to 0.034 in. In preferred embodiments, the lock line shaft 341 is comprised of a 304V stainless steel coil however other structures or materials may be used which provide kink resistance and compression strength.
[0194] Similarly, at least one proximal element line shaft 343 having a tubular shape may be present having a proximal element line lumen 342 . Proximal element lines 90 pass through this lumen 342 between the proximal element line handle 312 and the proximal elements 16 . Thus, the proximal element line shaft 343 extends through lumen 348 from the proximal end 322 to the distal end 324 of the shaft 302 . Therefore, the proximal element line shaft 343 typically has a length in the range of 48 to 60 in., an inner diameter in the range of 0.016 to 0.030 in., and an outer diameter in the range of 0.018 to 0.034 in. In preferred embodiments, the proximal element line shaft 343 is comprised of a 304V stainless steel coil however other structures or materials may be used which provide kink resistance and compression strength.
[0195] In this embodiment, the elongated bodies (compression coil 326 enclosed actuator rod 64 , tension cable 344 , lock line shaft 342 , proximal element line shaft 343 ) each “float” freely in inner lumen 348 within the support coil 346 and are fixed only at the proximal end 322 and distal end 324 of shaft 302 . The lumen 348 is typically filled and flushed with heparinized saline during use. Alternatively or in addition, the lumen 348 may be filled with one or more fillers, such as flexible rods, beads, extruded sections, gels or other fluids. Preferably the fillers allow for some lateral movement or deflection of the elongated bodies within lumen 348 but in some cases may restrict such movement. Typically, the elongated bodies are fixed at the proximal and distal ends of the shaft and are free to move laterally and rotationally therebetween. Such freedom of movement of the elongated bodies provides the shaft 302 with an increased flexibility as the elongated bodies self-adjust and reposition during bending and/or torqueing of the shaft 302 . It may be appreciated that the elongated bodies may not be fixed at the proximal and distal ends. The elongated bodies are simply unconstrained relative to the shaft 302 in at least one location so as to be laterally moveable within the lumen 348 . Preferably the elongated bodies are unrestrained in at least a distal portion of the catheter, e.g. 5-15 cm from the distal end 324 , so as to provide maximum flexibility in the distal portion.
[0196] It may be appreciated, however, that alternate shaft 302 designs may also be used. For example, referring to FIG. 39 , in this embodiment the shaft 302 again has a tubular shape with an inner lumen 348 and a support coil 346 disposed within the lumen 348 of shaft 302 . Filling the inner lumen 348 within the support coil 346 is an extrusion 334 having lumens through which pass a variety of elongated bodies, including the compression coil 326 enclosed actuator rod 64 , tension cable 344 , lock line shafts 342 , and proximal element line shafts 343 , as shown. The support coil 346 and elongated bodies may have the same geometries and be comprised of the same materials as described above in relation to FIG. 38 .
[0197] Alternatively, as shown in FIG. 40 , the shaft 302 may include an internal partition 350 to create multiple lumens within the shaft 302 . For example, the partition 350 may have a central lumen 352 for passage of the actuator rod 64 , optionally surrounded by the compression coil 326 . In addition, the partition 350 may also create at least one lock line lumen 340 for passage of a lock line 92 and at least one proximal element line lumen 341 for passage of a proximal element line 90 . Optionally, each of the lumens defined by partition 350 may be lined with a kink-resistant element, such as a coil as in previous embodiments.
[0198] FIGS. 40A-40B illustrate embodiments of the nose 318 of the shaft 302 . In FIG. 40A , the nose 318 comprises a tip ring 280 and a lock ring 282 . In preferred embodiments, Epoxy and PEBAX are deposited between the tip ring 280 and the lock ring 282 to bond them together. The lock ring 282 has a geometry to mate with the tip ring 280 to maintain relative alignment between the two. FIG. 40B illustrates another embodiment of the nose 318 of the shaft 302 . Here, the tip ring 280 is covered by a soft tip 284 to provide a more atraumatic tip and a smoother transition to the shaft.
[0199] C. Lock Line Arrangements
[0200] As mentioned previously, when lock lines 92 are present, the lines 92 pass through at least one lock line lumen 340 between the lock line handle 310 and the locking mechanism 106 . The lock lines 92 engage the release harnesses 108 of the locking mechanism 106 to lock and unlock the locking mechanism 106 as previously described. The lock lines 92 may engage the release harnesses 108 in various arrangements, examples of which are illustrated in FIGS. 41A-41C . In each embodiment, two lock line lumens 340 are present within the shaft 302 of the delivery catheter 300 terminating at the nose 318 . The lumens 340 are disposed on alternate sides of the actuator rod 64 so that each lumen 340 is directed toward a release harness 108 .
[0201] FIG. 41A illustrates an embodiment wherein two lock lines 92 , 92 ′ pass through a single lock line lumen 340 and are threaded through a release harness 108 on one side of the actuator rod 64 (the actuator rod 64 is shown without surrounding housing such as coupling structure, for clarity). The lock lines 92 , 92 ′ are then separated so that each lock line passes on an opposite side of the actuator rod 64 . The lock lines 92 , 92 ′ then pass through the release harness 108 ′ on the opposite side of the actuator rod 64 and continue together passing through a another single lock line lumen 340 ′. This lock line arrangement is the same arrangement illustrated in FIG. 26 .
[0202] FIG. 41B illustrates an embodiment wherein one lock line 92 passes through a single lock line lumen 340 , is threaded through a release harness 108 on one side of the actuator rod 64 , and is returned to the lock line lumen 340 . Similarly, another lock line 92 ′ passes through another single lock line lumen 340 ′, is threaded through a different release harness 108 ′ located on the opposite side of the actuator rod 64 , and is returned to the another single lock line lumen 340 ′.
[0203] FIG. 41C illustrates an embodiment wherein both lock lines 92 , 92 ′ pass through a single lock line lumen 340 . One lock line 92 is threaded through a release harness 108 on one side of the actuator rod 64 and is then passed through another lock line lumen 340 ′ on the opposite side of the actuator rod 64 . The other lock line 92 ′ is threaded through another release harness 108 ′ on the other side of the actuator rod 64 ′ and is then passed through the another lock line lumen 340 ′ with the previous lock line 92 .
[0204] It may be appreciated that a variety of lock line arrangements may be used and are not limited to the arrangements illustrated and described above. The various arrangements allow the harnesses 108 to be manipulated independently or jointly, allow various amounts of tension to be applied and vary the force required for removal of the lock lines when the fixation device is to be left behind. For example, a single lock line passing through one or two lumens may be connected to both release harnesses for simultaneous application of tension.
[0205] D. Proximal Element Line Arrangements
[0206] As mentioned previously, when proximal element lines 90 are present, the lines 90 pass through at least one proximal element line lumen 342 between the proximal element line handle 312 and at least one proximal element 16 . The proximal element lines 90 engage the proximal elements 16 to raise or lower the element 16 as previously described. The proximal element lines 90 may engage the proximal elements 16 in various arrangements, examples of which are illustrated in FIGS. 42A-42B . In each embodiment, two proximal element line lumens 342 are present within the shaft 302 of the delivery catheter 300 terminating at the nose 318 . The lumens 342 are disposed on alternate sides of the actuator rod 64 (the actuator rod 64 is shown without surrounding housing such as coupling structure, for clarity) so that each lumen 342 is directed toward a proximal element 16 .
[0207] FIG. 42A illustrates an embodiment wherein one proximal element line 90 passes through a single proximal element line lumen 342 . The proximal element line 90 is threaded through an eyelet 360 of a proximal element 16 on one side of the actuator rod 64 , passes over the actuator rod 64 and is threaded through an eyelet 360 ′ of another proximal element 16 ′ on the other side of the actuator rod 64 . The proximal element line 90 then passes through another single proximal element line lumen 342 ′. This proximal element line arrangement is the same arrangement illustrated in FIG. 26 .
[0208] FIG. 42B illustrates an embodiment wherein one proximal element line 90 passes through a single proximal element line lumen 342 , is threaded through an eyelet 360 of a proximal element 16 on one side of the actuator rod 64 , and is returned to the proximal element line lumen 342 . Similarly, another proximal element line 90 ′ passes through another single proximal element line lumen 342 ′ on the opposite side of the actuator rod 64 , and is returned to the another single proximal element line lumen 342 ′.
[0209] It may be appreciated that a variety of proximal element line arrangements may be used and are not limited to the arrangements illustrated and described above. The various arrangements allow the proximal elements to be manipulated independently or jointly, allow various amounts of tension to be applied and vary the force required for removal of the proximal element lines when the fixation device is to be left behind. For example, a single proximal element line passing through one or two lumens in shaft 302 may be used for simultaneous actuation of both proximal elements.
[0210] E. Main Body of Handle
[0211] FIG. 43 illustrates an embodiment of the handle 304 of the delivery catheter 300 . As mentioned previously, the actuator rod handle 316 , actuator rod control 314 , proximal element line handle 312 and lock line handle 310 are all joined with the main body 318 . The handle 304 further includes a support base 306 connected with the main body 308 . The main body 308 is slideable along the support base 306 to provide translation of the shaft 302 and the main body 308 is rotateable around the support base 306 to rotate the shaft.
[0212] FIG. 44 provides a partial cross-sectional view of the main body 308 of the handle 304 depicted in FIG. 43 . As shown, the main body 308 includes a sealed chamber 370 within which the actuator rod 64 , proximal element lines 90 and lock lines 92 are guided into the shaft 302 . The sealed chamber 370 is in fluid communication with the inner lumen 348 of shaft 302 and is typically filled with saline and flushed with heparin or heparinized saline. The sealed chamber 370 has a seal 372 along its perimeter to prevent leakage and the introduction of air to the chamber 370 . Any air in the chamber 370 may be bled from the chamber 370 by one or more luers 374 which pass through the main body 308 into the chamber 370 as illustrated in FIG. 43 . In this embodiment, the handle 304 includes two such luers 374 , one on each side of the main body 308 (second luer symmetrically positioned on backside of main body 308 in FIG. 43 , hidden from view). Referring now to FIG. 44 , the sealed chamber 370 also has various additional seals, such as an actuator rod seal 376 which surrounds the actuator rod 64 where the actuator rod 64 enters the sealed chamber 370 , and a shaft seal 378 which surrounds the shaft 302 where the shaft 302 enters the sealed chamber 370 .
[0213] F. Lock Line Handle and Proximal Element Line Handle
[0214] As mentioned previously, the lock lines 92 may be may be extended, retracted, loaded with various amounts of tension or removed using the lock line handle 310 . Likewise, the proximal element lines 90 may be extended, retracted, loaded with various amounts of tension or removed using the proximal element line handle 312 . Both of these handles 310 , 312 may be similarly designed to manipulate the appropriate lines 90 , 92 passing therethrough.
[0215] FIG. 45 illustrates an embodiment of a lock line handle 310 having lock lines 92 passing therethrough. The lock line handle 310 has a distal end 384 , a proximal end 382 and an elongate shaft 383 therebetween. The distal end 382 is positionable within the sealed chamber 370 so that the proximal end 382 extends out of the chamber 370 , beyond the main body 308 . The free ends of the lock lines 92 are disposed near the proximal end 382 , passing through the wall of the handle 310 near a threaded nub 390 . The handle 310 further includes a cap 388 which is positionable on the nub 309 . Internal threading with the cap 388 mates with the threading on the threaded nub 390 so that the cap 388 holds the free ends of the lock lines 92 between the cap 388 and the nub 390 and/or other portions of the handle 310 by friction. The lock lines 92 pass through a central lumen (not shown) of the elongate shaft 383 , extend through the sealed chamber 370 (as shown in FIG. 44 ) and extend through the shaft 302 to the locking mechanism 106 .
[0216] Disposed near the distal end 384 of the handle 310 is at least one wing 392 . In the embodiment of FIG. 45 , two wings 392 are present, each wing 392 disposed on opposite sides of the elongate shaft 383 . The wings 392 extend radially outwardly and curve proximally so that a portion is parallel to the elongate shaft 383 , as shown. It may be appreciated that the wings 392 may alternatively have the shape of solid or continuous protrusions which extend radially and have a portion which is parallel to the elongate shaft 383 . The wings 392 are used to hold the lock line handle 310 in a desired position which in turn holds the lock under a desired load of tension, as will be described further below. The handle 310 also includes a finger grip 386 near the proximal end 382 which extends radially outwardly in alignment with the radial extension of the at least one wing 392 . Thus, the user may determine the orientation of the wings 392 within the sealed chamber 370 from the orientation of the finger grip 386 outside of the main body 308 . The finger grip 386 may also serve an ergonomic purpose to assist in manipulating the handle 310 .
[0217] The portion of the wings 392 parallel to the elongate shaft 383 have grooves or serrations 394 . The serrations 394 are used to apply tension to the lock lines 92 . As shown in FIG. 45A , the lock line handle 310 is positioned within a semi-tube 400 which is disposed within the sealed chamber 370 . The semi-tube 400 comprises a top half 402 and a bottom half 404 , each half 402 , 404 having grooves or serrations 406 which mate with the serrations 394 of the wings 392 . Thus, when the wings 392 are rotated to mate the serrations 394 , 406 , as shown in FIG. 46A , the elongate shaft 383 is held in place. Likewise, the wings 392 may be rotated, as shown in FIG. 46B , so that the wings 392 are disposed between the halves 402 , 404 and the serrations 394 , 406 are disengaged. In this position, the shaft 383 may be translated to apply or release tension in the lock lines 92 . Thus, tension in the lines 92 may be adjusted by rotating the shaft 383 to disengage the serrations 394 , 406 , translating the shaft 383 and then rotating the shaft 383 back to reengage the serrations 394 , 406 . Alternatively, the finger grip 386 may be pulled to apply tension to the lock lines 92 . Pulling the finger grip 386 translates the lock line handle 310 within the semi-tube 400 . Such translation is achievable due to angling of the serrations 394 , 406 and flexibility of wings 382 . However, the angling of the serrations 394 , 406 prevents translation in the opposite direction, i.e. by pushing the finger grip 386 . Therefore, to release tension from the lock lines 92 , the shaft 383 is rotated to disengage the serrations 394 , 406 , allowing translation of the shaft 383 , and then the shaft 383 is rotated back to reengage the serrations 394 , 406 .
[0218] To remove the lock lines 92 , the cap 388 is removed from the threaded nub 390 exposing the free ends of the lock lines 92 . If one lock line 92 is present having two free ends, continuous pulling on one of the free ends draws the entire length of lock line 92 out of the catheter 300 . If more than one lock line 92 is present, each lock line 92 will have two free ends. Continuous pulling on one of the free ends of each lock line 92 draws the entire length of each lock line 92 out of the catheter 300 .
[0219] It may be appreciated that the proximal element line handle 312 has corresponding features to the lock line handle 310 and operates in the same manner as illustrated in FIGS. 45A , 46 A- 46 B. It may also be appreciated that other mechanisms may be used for manipulating the lock lines 92 and proximal element lines 90 , such as including buttons, springs, levers and knobs.
[0220] G. Actuator Rod Control and Handle
[0221] The actuator rod 64 may be manipulated using the actuator rod control 314 and the actuator rod handle 316 . FIG. 47 provides a cross-sectional view of a portion of the handle 304 which includes the actuator rod control 314 and the actuator rod handle 316 . The actuator rod handle 316 is located at the proximal end of the handle 314 . The actuator rod handle 316 is fixedly attached to the proximal end of the actuator rod 64 . The actuator rod 64 is inserted through a collet 426 which is disposed within a holder 428 as shown. The holder 428 has external threads 434 which mate with internal threads 432 of the actuator rod control 314 . Thus, rotation of the actuator rod control 314 causes the holder 428 to translate along the actuator rod control 314 by action of the threading, as will be described in more detail below. The actuator rod control 314 is rotatably coupled with the main body 308 of the handle 304 and is held in place by a lip 430 .
[0222] Referring to FIG. 47A , the actuator rod control 314 may be manually rotated in a clockwise or counter clockwise direction, as indicated by arrow 436 . Rotation of the actuator rod control 314 translates (extends or retracts) the actuator rod 64 to manipulate the distal elements 18 of the fixation device 14 . Specifically, rotation of the actuator rod control 314 causes the external threads 434 of the adjacent holder 428 to translate along the mated internal threads 432 of the actuator rod control 314 . Rotation of the holder 428 itself is prevented by holding pins 424 which protrude from the holder 428 and nest into grooves 438 in the main body 308 of the handle 304 . As the holder 428 translates, each holding pin 424 translates along its corresponding groove 438 . Since the collet 426 is attached to the holder 428 , the collet 426 translates along with the holder 428 . To simultaneously translate the actuator rod 64 , the actuator rod 64 is removably attached to the collet 426 by a pin 422 . The pin 422 may have any suitable form, including a clip-shape which partially wraps around the collet 426 as illustrated in FIG. 47 . Thus, rotation of the actuator rod control 314 provides fine control of translation of the actuator rod 64 and therefore fine control of positioning the distal elements 18 .
[0223] Referring to FIG. 47B , removal of the pin 422 , as shown, allows disengagement of the actuator rod handle 316 and fixedly attached actuator rod 64 from the collet 426 . Once disengaged, the actuator rod 64 may be rotated, as indicated by arrow 440 , by manually rotating the actuator rod handle 316 . As described previously, rotation of the actuator rod 64 engages or disengages the threaded joiner 332 of the delivery catheter 300 from the threaded stud 74 of the fixation device 14 . This is used to attach or detach the fixation device 14 from the delivery catheter 300 . In addition, when the actuator rod 64 is in the disengaged state, the actuator rod 64 may optionally be retracted and optionally removed from the catheter 300 by pulling the actuator rod handle 316 and withdrawing the actuator rod 64 from the handle 304 .
[0224] Depending on the application, the location of the target site, and the approach selected, the devices of the invention may be modified in ways well known to those of skill in the art or used in conjunction with other devices that are known in the art. For example, the delivery catheter may be modified in length, stiffness, shape and steerability for a desired application. Likewise, the orientation of the fixation device relative to the delivery catheter may be reversed or otherwise changed. The actuation mechanisms may be changed to be driven in alternate directions (push to open, pull to close, or pull to open, push to close). Materials and designs may be changed to be, for example, more flexible or more rigid. And the fixation device components may be altered to those of different size or shape. Further, the delivery catheter of the present invention may be used to deliver other types of devices, particularly endovascular and minimally invasive surgical devices used in angioplasty, atherectomy, stent-delivery, embolic filtration and removal, septal defect repair, tissue approximation and repair, vascular clamping and ligation, suturing, aneurysm repair, vascular occlusion, and electrophysiological mapping and ablation, to name a few. Thus, the delivery catheter of the present invention may be used for applications in which a highly flexible, kink-resistant device is desirable with high compressive, tensile and torsional strength.
[0225] H. Pusher Handle Design
[0226] After engaging successfully grasping the leaflets, usually at an angle between 120 and 180 degrees, the actuator rod 64 is manually rotated to manipulate the distal elements of the fixation device. This moves the distal elements proximally to an angle, such as 60 degrees as shown in FIG. 11B . However, with reference to FIG. 15B , the gripper pusher 81 and the proximal element actuators 90 also need to be retracted as angle between the distal elements 18 is reduced. FIG. 70 shows an embodiment of a handle that coordinates these movements. As shown in the figure, the proximal element line handle 312 of FIG. 44 is fitted with a spring loaded pusher attachment 414 that is connected to a gripper pusher actuator 411 that extends to the gripper pusher 81 of the fixation device. This spring loaded pusher attachment 414 surrounds, but moves independently of the proximal element line 90 . The spring 413 functions to provide a tension on the proximal element line 90 by exerting a small force on the gripper pusher 81 relative to the gripper pusher actuator. Further, a gripper pusher actuator wire 412 is coupled to the actuator rod 64 so that when the actuator rod 64 is actuated to close the distal elements 18 , the gripper pusher 81 is retracted. As shown in FIG. 70 , the pusher actuator wire 412 interacts with the spring loaded pusher attachment 414 to retract the spring loaded pusher attachment 414 when the distal elements 18 are closed. On the other hand, the distal end of the pusher actuator wire 412 is configured to slide distally with respect to the spring loaded pusher attachment 414 so that the distal movement of the gripper pusher 81 is independent of the movement of the distal elements 18 . This permits separation between the proximal elements 16 and the distal elements 18 to aid in grasping leaflets. Lastly, due to the spring coupling between the spring loaded pusher attachment 414 and the proximal element line handle 312 , the proximal element actuator 90 is also retracted in combination with the retracting of the gripper pusher actuator 411 . Notably, due to the spring coupling via the spring 413 , the proximal element actuator 90 is permitted further travel than the gripper pusher actuator 411 . This additional travel is permitted via expansion of the spring 413 and functions to remove slack in the proximal element actuator as the angle between the proximal elements 16 and the distal elements 18 is reduced.
V. Multi-Catheter Guiding System
[0227] A. Overview of Guiding System
[0228] Referring to FIG. 48 , an embodiment of a multi-catheter guiding system 1 of the present invention is illustrated. The system 1 comprises an outer guide catheter 1000 , having a proximal end 1014 , a distal end 1016 , and a central lumen 1018 therethrough, and an inner guide catheter 1020 , having a proximal end 1024 , distal end 1026 and central lumen 1028 therethrough, wherein the inner guide catheter 1020 is positioned coaxially within the central lumen 1018 of the outer guide catheter 1000 , as shown. The distal ends 1016 , 1026 of catheters 1000 , 1020 , respectively, are sized to be passable to a body cavity, typically through a body lumen such as a vascular lumen. Thus, the distal end 1016 preferably has an outer diameter in the range of approximately 0.040 in. to 0.500 in., more preferably in the range of 0.130 in. to 0.320 in. The central lumen 1018 is sized for the passage of the inner guide catheter 1020 ; the distal end 1026 preferably has an outer diameter in the range of approximately 0.035 in. to 0.280 in., more preferably 0.120 in to 0.200 in. The central lumen 1028 is sized for the passage of a variety of devices therethrough. Therefore, the central lumen 1028 preferably has an inner diameter in the range of approximately 0.026 in. to 0.450 in., more preferably in the range of 0.100 in. to 0.180 in.
[0229] FIG. 48 illustrates an interventional catheter 1030 positioned within the inner guide catheter 1020 which may optionally be included in system 1 , however other interventional devices may be used. The interventional catheter 1030 has a proximal end 1034 and a distal end 1036 , wherein an interventional tool 1040 is positioned at the distal end 1036 . In this embodiment, the interventional tool 1040 comprises a detachable fixation device or clip. Optionally, the interventional catheter 1030 may also include a nosepiece 1042 having a stop 1043 , as shown. The stop 1043 prevents the interventional tool 1040 from entering the central lumen 1028 of the inner guide catheter 1020 . Thus, the interventional catheter 1030 may be advanced and retracted until the stop 1043 contacts the distal end 1026 of the inner guiding catheter 1020 preventing further retraction. This may provide certain advantages during some procedures. It may be appreciated that in embodiments which include such a stop 1043 , the interventional catheter 1030 would be pre-loaded within the inner guide catheter 1020 for advancement through the outer guiding catheter 1000 or both the interventional catheter 1030 and the inner guiding catheter 1020 would be pre-loaded into the outer guiding catheter 1000 for advancement to the target tissue. This is because the stop 1043 prevents advancement of the interventional catheter 1030 through the inner guiding catheter 1020 .
[0230] The outer guide catheter 1000 and/or the inner guide catheter 1020 are precurved and/or have steering mechanisms, embodiments of which will be described later in detail, to position the distal ends 1016 , 1026 in desired directions. Precurvature or steering of the outer guide catheter 1000 directs the distal end 1016 in a first direction to create a primary curve while precurvature and/or steering of the inner guide catheter 1020 directs distal end 1026 in a second direction, differing from the first, to create a secondary curve. Together, the primary and secondary curves form a compound curve. Advancement of the interventional catheter 1030 through the coaxial guide catheters 1000 , 1020 guides the interventional catheter 1030 through the compound curve toward a desired direction, usually in a direction which will allow the interventional catheter 1030 to reach its target.
[0231] Steering of the outer guide catheter 1000 and inner guide catheter 1020 may be achieved by actuation of one or more steering mechanisms. Actuation of the steering mechanisms is achieved with the use of actuators which are typically located on handles connected with each of the catheters 1000 , 1020 . As illustrated in FIG. 48 , handle 1056 is connected to the proximal end 1014 of the outer guide catheter 1000 and remains outside of the patient's body during use. Handle 1056 includes steering actuator 1050 which may be used to bend, arc or reshape the outer guide catheter 1000 , such as to form a primary curve. Handle 1057 is connected to the proximal end (not shown) of the inner guide catheter 1020 and may optionally join with handle 1056 to form one larger handle, as shown. Handle 1057 includes steering actuator 1052 which may be used to bend, arc or reshape the inner guide catheter 1020 , such as to form a secondary curve and move the distal end 1026 of the inner guide catheter 1020 through an angle theta, as will be described in a later section.
[0232] In addition, locking actuators 1058 , 1060 may be used to actuate locking mechanisms to lock the catheters 1000 , 1020 in a particular position. Actuators 1050 , 1052 , 1058 , 1060 are illustrated as buttons, however it may be appreciated that these and any additional actuators located on the handles 1056 , 1057 may have any suitable form including knobs, thumbwheels, levers, switches, toggles, sensors or other devices. Other embodiments of the handles will be described in detail in a later section.
[0233] In addition, the handle 1056 may include a numerical or graphical display 1061 of information such as data indicating the position the catheters 1000 , 1020 , or force on actuators. It may also be appreciated that actuators 1050 , 1052 , 1058 , 1060 and any other buttons or screens may be disposed on a single handle which connects with both the catheters 1000 , 1020 .
[0234] B. Example Positions
[0235] FIGS. 49A-49D illustrate examples of positions that the catheters 1000 , 1020 may hold. Referring to FIG. 49A , the outer guide catheter 1000 may be precurved and/or steered into a position which includes a primary curve 1100 . The primary curve 1100 typically has a radius of curvature 1102 in the range of approximately 0.125 in. to 1.000 in., preferably in the range of approximately 0.250 in. to 0.500 in. or forms a curve in the range of approximately 0° to 120°. As shown, when the position includes only a primary curve 1100 , the distal end 16 lies in a single plane X. An axis x, transversing through the center of the central lumen 18 at the distal end 16 , lies within plane X.
[0236] Referring to FIG. 49B , the inner guide catheter 1020 extends through the central lumen 1018 of the outer guide catheter 1000 . The inner guide catheter 1020 may be precurved and/or steered into a position which includes a secondary curve 1104 . The secondary curve 1104 typically has a radius of curvature 10600 in the range of approximately 0.050 in. to 0.750 in., preferably in the range of approximately 0.125 in. to 0.250 in. or forms a curve in the range of approximately 0° to 180°. The secondary curve 1104 can lie in the same plane as the primary curve 1100 , plane X, or it can lie in a different plane, such as plane Z as shown. In this example, plane Z is substantially orthogonal to plane X. Axis z, transversing through the center of the central lumen 1028 of the inner guide catheter 1020 at the distal end 1026 , lies within plane Z. In this example, axis x and axis z are at substantially 90 degree angles to each other; however, it may be appreciated that axis x and axis z may be at any angle in relation to each other. Also, although in this example the primary curve 1100 and the secondary curve 1104 lie in different planes, particularly in substantially orthogonal planes, the curves 1100 , 1104 may alternatively lie in the same plane.
[0237] Referring now to FIG. 49C , the inner guide catheter 1020 may be further manipulated to allow the distal end 1026 to move through an angle theta 1070 . The angle theta 1070 is in the range of approximately −180° to +180°, typically in the range of −90° to +90°, possibly in the range of −60° to +60°, −45° to +45°, −30° to +30° or less. As shown, the angle theta 1070 lies within a plane Y. In particular, axis y, which runs through the center of the central lumen 1028 at the distal end 1026 , forms the angle theta 1070 with axis z. In this example, plane Y is orthogonal to both plane X and plane Z. Axes x, y, z all intercept at a point within the central lumen 1028 which also coincides with the intersection of planes X, Y, Z.
[0238] Similarly, FIG. 49D illustrates movement of the distal end 1026 through an angle theta 1070 on the opposite side of axis z. Again, the angle theta 1070 is measured from the axis z to the axis y, which runs through the center of the central lumen 1016 at the distal end 1026 . As shown, the angle theta 1070 lies in plane Y. Thus, the primary curve 1100 , secondary curve 1104 , and angle theta 1070 can all lie in different planes, and optionally in orthogonal planes. However, it may be appreciated that the planes within which the primary curve 1100 , secondary curve 1104 and angle theta 1070 lie may be mutually dependent and therefore would allow the possibility that some of these lie within the same plane.
[0239] In addition, the outer guide catheter 1000 may be pre-formed and/or steerable to provide additional curves or shapes. For example, as illustrated in FIG. 50A , an additional curve 1110 may be formed by the outer guide catheter 1000 proximal to the primary curve 1100 . In this example, the curve 1110 provides lift or raises the distal end 1016 of the outer guide catheter 1000 , which in turn raises the distal end 1026 of the inner guide catheter 1020 . Such lifting is illustrated in FIG. 50B . Here, the system 1 is shown prior to lifting in dashed line wherein the axis y′ passes through the intersection of axis z and axis x′. After application of curve 1110 , the distal portion of the system 1 is lifted in the direction of axis z so that axis x′ is raised to axis x″ and axis y′ is raised to axis y″. This raises distal end 1026 to a desired height.
[0240] The articulated position of the multi-catheter guiding system 1 illustrated in FIGS. 49A-49D and FIGS. 50A-50B is particularly useful for accessing the mitral valve. FIGS. 51A-51D illustrate a method of using the system 1 for accessing the mitral valve MV. To gain access to the mitral valve, the outer guide catheter 1000 may be tracked over a dilator and guidewire from a puncture in the femoral vein, through the inferior vena cava and into the right atrium. As shown in FIG. 51A , the outer guide catheter 1000 may be punctured through a fossa F in the interatrial septum S. The outer guide catheter 1000 is then advanced through the fossa F and curved by the primary curve 1100 so that the distal end 1016 is directed over the mitral valve MV. Again, it may be appreciated that this approach serves merely as an example and other approaches may be used, such as through the jugular vein, femoral artery, port access or direct access, to name a few. Positioning of the distal end 1016 over the mitral valve MV may be accomplished by precurvature of the outer guide catheter 1000 , wherein the catheter 1000 assumes this position when the dilator and guidewire are retracted, and/or by steering of the outer guide catheter 1000 to the desired position. In this example, formation of the primary curve 1100 moves the distal end 1016 within a primary plane, corresponding to previous plane X, substantially parallel to the valve surface. This moves the distal end 1016 laterally along the short axis of the mitral valve MV, and allows the distal end 1016 to be centered over the opening O between the leaflets LF.
[0241] Referring to FIG. 51B , the inner guide catheter 1020 is advanced through the central lumen 1018 of the outer guide catheter 1000 and the distal end 1026 is positioned so that the central lumen 1028 is directed toward the target tissue, the mitral valve MV. In particular, the central lumen 1028 is to be directed toward a specific area of the mitral valve MV, such as toward the opening O between the valve leaflets LF, so that a particular interventional procedure may be performed. In FIG. 51B , the inner guide catheter 1020 is shown in a position which includes a secondary curve 1104 in a secondary plane, corresponding to previous plane Z. Formation of the secondary curve 1104 moves the distal end 1026 vertically and angularly between the commissures C, directing the central lumen 1028 toward the mitral valve MV. In this position an interventional device or catheter 1030 which is passed through the central lumen 1028 would be directed toward and/or through the opening O. Although the primary curve 1100 and the secondary curve 1104 may be varied to accommodate different anatomical variations of the valve MV and different surgical procedures, further adjustment may be desired beyond these two curvatures for proper positioning of the system 1 .
[0242] Referring to FIG. 51C , the distal end 1026 of the inner guide catheter 1020 may be positioned through an angle theta 1070 . This moves the distal end 1026 vertically and angularly through a theta plane, corresponding to previous plane Y. Movement of the distal end 1026 through the angle theta 1070 in either direction is shown in dashed line in FIG. 51C . Such movement can be achieved by precurvature and/or by steering of the catheter 1020 . Consequently, the central lumen 1028 can be directed toward the mitral valve MV within a plane which differs from the secondary plane. After such movements, the inner guide catheter 1020 will be in a position so that the opening of the central lumen 1028 at the end 1016 faces the desired direction. In this case, the desired direction is toward the center of and orthogonal to the mitral valve.
[0243] In some instances, it is desired to raise or lower the distal end 1026 so that it is at a desired height in relation to the mitral valve MV. This may be accomplished by precurvature and/or by steering of the outer guide catheter 1000 to form additional curve 1110 . Generally this is used to lift the distal end 1026 above the mitral MV wherein such lifting was illustrated in FIG. 50B .
[0244] When the curvatures in the catheters 1000 , 1020 are formed by steering mechanisms, the steering mechanisms may be locked in place by a locking feature. Locking can provide additional stiffness and stability in the guiding system 1 for the passage of interventional devices or catheters 1030 therethrough, as illustrated in FIG. 48 . The interventional catheter 1030 can be passed through the central lumen 1028 toward the target tissue, in this case the mitral valve MV. Positioning of the distal end 1026 over the opening O, as described above, allows the catheter 1030 to pass through the opening O between the leaflets LF if desired, as shown in FIG. 51D . At this point, any desired procedure may be applied to the mitral valve for correction of regurgitation or any other disorder.
[0245] C. Steering Mechanisms
[0246] As described previously, the curvatures may be formed in the catheters 1000 , 1020 by precurving, steering or any suitable means. Precurving involves setting a specific curvature in the catheter prior to usage, such as by heat setting a polymer or by utilizing a shape-memory alloy. Since the catheters are generally flexible, loading of the catheter on a guidewire, dilator obturator or other introductory device straightens the catheter throughout the curved region. Once the catheter is positioned in the anatomy, the introductory device is removed and the catheter is allowed to relax back into the precurved setting.
[0247] To provide a higher degree of control and variety of possible curvatures, steering mechanisms may be used to create the curvatures and position the catheters. In some embodiments, the steering mechanisms comprise cables or pullwires within the wall of the catheter. As shown in FIG. 52A , the outer guide catheter 1000 may include a pullwire 1120 slidably disposed in lumens within the wall of the catheter 1000 extending to the distal end 1016 . By applying tension to the pullwire 1120 in the proximal direction, the distal end 1016 curves in the direction of the pullwire 1120 as illustrated by arrow 1122 . Likewise, as shown in FIG. 52B , placement of the pullwire 1120 along the opposite side of the catheter 1000 will allow the distal end 1016 to curve in the opposite direction, as illustrated by arrow 1124 , when tension is applied to the pullwire 1120 . Thus, referring to FIG. 52C , diametrically opposing placement of pullwires 1120 within the walls of the catheter 1000 allows the distal end 1016 to be steered in opposite directions. This provides a means of correcting or adjusting a curvature. For example, if tension is applied to one pullwire to create a curvature, the curvature may be lessened by applying tension to the diametrically opposite pullwire. Referring now to FIG. 52D , an additional set of opposing pullwires 1120 ′ may extend within the wall of the catheter 1000 as shown. This combination of pullwires 1120 , 1120 ′ allows curvature of the distal end in at least four directions illustrated by arrows 1122 , 1124 , 1126 , 1128 . In this example, pullwires 1120 create the primary curve 1100 of the outer guide catheter 1000 and the pullwires 1120 ′ create the lift. It may be appreciated that FIGS. 52A-52D also pertain to the inner guide catheter 1020 . For example, in FIG. 52D , pullwires 1120 may create the secondary curve 1104 of the inner guide catheter 1020 and the pullwires 1120 ′ create the angle theta 1070 .
[0248] Such pullwires 1120 and/or pullwires 1120 ′ and associated lumens may be placed in any arrangement, singly or in pairs, symmetrically or nonsymmetrically and any number of pullwires may be present. This may allow curvature in any direction and about various axes. The pullwires 1120 , 1120 ′ may be fixed at any location along the length of the catheter by any suitable method, such as gluing, tying, soldering, or potting, to name a few. When tension is applied to the pullwire, the curvature forms from the point of attachment of the pullwire toward the proximal direction. Therefore, curvatures may be formed throughout the length of the catheter depending upon the locations of the points of attachment of the pullwires. Typically, however, the pullwires will be attached near the distal end of the catheter, optionally to an embedded tip ring 280 , illustrated in FIG. 52E . As shown, the pullwire 1120 passes through an orifice 286 in the tip ring 280 , forms a loop shape and then passes back through the orifice 286 and travels back up through the catheter wall (not shown). In addition, the lumens which house the pullwires may be straight, as shown in FIGS. 52A-52D , or may be curved.
[0249] D. Catheter Construction
[0250] The outer guide catheter 1000 and inner guide catheter 1020 may have the same or different construction which may include any suitable material or combination of materials to create the above described curvatures. For clarity, the examples provided will be in reference to the outer guide catheter 1000 , however it may be appreciated that such examples may also apply to the inner guide catheter 1020 .
[0251] In embodiments in which the catheter is precurved rather than steerable or in addition to being steerable, the catheter 1000 may be comprised of a polymer or copolymer which is able to be set in a desired curvature, such as by heat setting. Likewise, the catheter 1000 may be comprised of a shape-memory alloy.
[0252] In embodiments in which the catheter is steerable, the catheter 1000 may be comprised of one or more of a variety of materials, either along the length of the catheter 1000 or in various segments. Example materials include polyurethane, Pebax, nylon, polyester, polyethylene, polyimide, polyethylenetelephthalate (PET), polyetheretherketone (PEEK). In addition, the walls of the catheter 1000 may be reinforced with a variety of structures, such as metal braids or coils. Such reinforcements may be along the length of the catheter 1000 or in various segments.
[0253] For example, referring to FIG. 53A , the catheter 1000 may have a proximal braided segment 1150 , a coiled segment 1152 and distal braided segment 1154 . The proximal braided segment 1150 provides increased column strength and torque transmission. The coiled segment 1152 provides increased steerability. The distal braided segment 1154 provides a blend of steerability and torque/column strength. In another example, referring to FIG. 53B , the outer guiding catheter 1000 has a proximal double-layer braided segment 1151 and a distal braided segment 1154 . Thus, the proximal double-layer segment 1151 comprises a multi-lumen tube 1160 (having steering lumens 1162 for pullwires, distal ends of the steering lumens 1162 optionally embedded with stainless steel coils for reinforcement, and a central lumen 1163 ), an inner braided layer 1164 , and an outer braided layer 1166 , as illustrated in the cross-sectional view of FIG. 53C . Similarly, FIG. 53D provides a cross-sectional view of the distal braided segment 1154 comprising the multi-lumen tube 1160 and a single braided layer 1168 . In a further example, referring to FIG. 53E , the inner guiding catheter 1020 comprises a multi-lumen tube 1160 without reinforcement at its proximal end, a single braided layer middle segment 1170 and a single braided layer distal segment 1171 . Each of the single braided layer segments 1170 , 1171 have a multi-lumen tube 1160 and a single layer of braiding 1168 , as illustrated in cross-sectional view FIG. 53F . However, the segments 1170 , 1171 are comprised of polymers of differing durometers, typically decreasing toward the distal end.
[0254] FIG. 53G illustrates an other example of a cross-section of a distal section of an outer guiding catheter 1000 . Here, layer 1130 comprises 55D Pebax and has a thickness of approximately 0.0125 in. Layer 1131 comprises a 30 ppi braid and has a thickness of approximately 0.002 in. by 0.0065 in. Layer 1132 comprises 55D Pebax and has a thickness of approximately 0.006 in. Layer 1133 comprises 30 ppi braid and has a thickness of approximately 0.002 in by 0.0065 in. And finally, layer 1134 comprises Nylon 11 and includes steering lumens for approximately 0.0105 in. diameter pullwires 1120 . Central lumen 1163 is of sufficient size for passage of devices.
[0255] FIGS. 53H-53I illustrate additional examples of cross-sections of an inner guiding catheter 1020 , FIG. 53I illustrating a cross-section of a portion of the distal end and FIG. 53I illustrating a cross-section of a more distal portion of the distal end. Referring to FIG. 53H , layer 1135 comprises 40D polymer and has a thickness of approximately 0.0125 in. Layer 1136 comprises a 30 ppi braid and has a thickness of approximately 0.002 in. by 0.0065 in. Layer 1137 comprises 40D polymer and has a thickness of approximately 0.006 in. Layer 1138 comprises a 40D polymer layer and has a thickness of approximately 0.0035 in. And finally, layer 1139 comprises a 55D liner. In addition, coiled steering lumens are included for approximately 0.0105 in. diameter pullwires 1120 . And, central lumen 1163 is of sufficient size for passage of devices. Referring to FIG. 53I , layer 1140 comprises a 40D polymer, layer 1141 comprises a 35D polymer, layer 1142 comprises a braid and layer 1143 comprises a liner. In addition, coiled steering lumens 1144 are included for pullwires. And, central lumen 1163 is of sufficient size for passage of devices.
[0256] FIGS. 54A-54C illustrate an embodiment of a keying feature which may be incorporated into the catheter shafts. The keying feature is used to maintain relationship between the inner and outer guide catheters to assist in steering capabilities. As shown in FIG. 54A , the inner guide catheter 1020 includes one or more protrusions 1400 which extend radially outwardly. In this example, four protrusions 1400 are present, equally spaced around the exterior of the catheter 1020 . Likewise, the outer guide catheter 1000 includes corresponding notches 1402 which align with the protrusions 1400 . Thus, in this example, the catheter 1000 includes four notches equally spaced around its central lumen 1018 . Thus, the inner guide catheter 1020 is able to be translated within the outer guide catheter 1000 , however rotation of the inner guide catheter 1020 within the outer guide catheter 1000 is prevented by the keying feature, i.e. the interlocking protrusions 1400 and notches 1402 . Such keying helps maintain a known correlation of position between the inner guide catheter 1020 and outer guide catheter 1000 . Since the inner and outer guide catheters 1020 , 1000 form curvatures in different directions, such keying is beneficial to ensure that the compound curvature formed by the separate curvatures in the inner and outer guide catheters 1020 , 1000 is the compound curvature that is anticipated. Keying may also increase stability wherein the curvatures remain in position reducing the possibility of compensating for each other.
[0257] FIG. 54B illustrates a cross-sectional view of the outer guiding catheter 1000 of FIG. 54A . Here, the catheter 1000 includes a notched layer 1404 along the inner surface of central lumen 1018 . The notched layer 1404 includes notches 1402 in any size, shape, arrangement and number. Optionally, the notched layer 1404 may include lumens 1406 , typically for passage of pullwires 1120 . However, the lumens 1406 may alternatively or in addition be used for other uses. It may also be appreciated that the notched layer 1404 may be incorporated into the wall of the catheter 1000 , such as by extrusion, or may be a separate layer positioned within the catheter 1000 . Further, it may be appreciated that the notched layer 1404 may extend the entire length of the catheter 1000 or one or more portions of the length of the catheter 1000 , including simply a small strip at a designated location along the length of the catheter 1000 .
[0258] FIG. 54C illustrates a cross-sectional view of the inner guiding catheter 1020 of FIG. 54A . Here, the catheter 1020 includes protrusions 1400 along the outer surface of the catheter 1020 . The protrusions 1400 may be of any size, shape, arrangement and number. It may be appreciated that the protrusions 1400 may be incorporated into the wall of the catheter 1020 , such as by extrusion, may be included in a separate cylindrical layer on the outer surface of the catheter 1020 , or the protrusions 1400 may be individually adhered to the outer surface of the catheter 1020 . Further, it may be appreciated that the protrusions 1400 may extend the entire length of the catheter 1000 or one or more portions of the length of the catheter 1020 , including simply a small strip at a designated location along the length of the catheter 1020 .
[0259] Thus, the keying feature may be present along one or more specific portions of the catheters 1000 , 1020 or may extend along the entire length of the catheters 1000 , 1020 . Likewise, the notches 1402 may extend along the entire length of the outer guiding catheter 1020 while the protrusions 1400 extend along discrete portions of the inner guiding catheter 1000 and vice versa. It may further be appreciated that the protrusions 1400 may be present on the inner surface of the outer guiding catheter 1000 while the notches 1402 are present along the outer surface of the inner guiding catheter 1020 .
[0260] Alternatively or in addition, one or more steerable portions of the catheter 1000 may comprise a series of articulating members 1180 as illustrated in FIG. 55A . Exemplary embodiments of steerable portions of catheters comprising such articulating members 1180 are described in U.S. Pat. No. 7,682,319 (Attorney Docket No. 020489-001210US) incorporated herein by reference for all purposes. FIG. 55B illustrates the outer guide catheter 1000 having a steerable portion comprising articulating members 1180 at its distal end 1016 .
[0261] Briefly, referring to FIG. 55A , each articulating member 1180 may have any shape, particularly a shape which allows interfitting or nesting as shown. In addition, it is desired that each member 1180 have the capability of independently rotating against an adjacent articulating member 1180 . In this embodiment, the articulating members 1180 comprise interfitting domed rings 1184 . The domed rings 1184 each include a base 1188 and a dome 1186 . The base 1188 and dome 1186 have a hollow interior which, when the domed rings 1184 are interfit in a series, forms a central lumen 1190 . In addition, the dome 1186 allows each articulating member 1180 to mate against an inner surface of an adjacent domed ring 1184 .
[0262] The interfitting domed rings 1184 are connected by at least one pullwire 1120 . Such pullwires typically extend through the length of the catheter 1000 and at least one of the interfitting domed rings 1184 to a fixation point where the pullwire 1120 is fixedly attached. By applying tension to the pullwire 1120 , the pullwire 1120 arcs the series of interfitting domed rings 1184 proximal to the attachment point to form a curve. Thus, pulling or applying tension on at least one pullwire, steers or deflects the catheter 1000 in the direction of that pullwire 1120 . By positioning various pullwires 1120 throughout the circumference of the domed rings 1184 , the catheter 1000 may be directed in any number of directions.
[0263] Also shown in FIG. 55A , each interfitting domed ring 1184 may comprise one or more pullwire lumens 1182 through which the pullwires 1120 are threaded. Alternatively, the pullwires 1120 may be threaded through the central lumen 1190 . In any case, the pullwires are attached to the catheter 1000 at a position where a desired curve is to be formed. The pullwires 1120 may be fixed in place by any suitable method, such as soldering, gluing, tying, welding or potting, to name a few. Such fixation method is typically dependent upon the materials used. The articulating members 1180 may be comprised of any suitable material including stainless steel, various metals, various polymers or co-polymers. Likewise the pullwires 1120 may be comprised of any suitable material such as fibers, sutures, metal wires, metal braids, or polymer braids.
[0264] E. Handles
[0265] As mentioned previously, manipulation of the guide catheters 1000 , 1020 is achieved with the use of handles 1056 , 1057 attached to the proximal ends of the catheters 1000 , 1020 . FIG. 56 illustrates a preferred embodiment of handles 1056 , 1057 . As shown, handle 1056 is attached to the proximal end 1014 of outer guide catheter 1000 and handle 1057 is attached to the proximal end 1024 of inner guide catheter 1020 . Inner guide catheter 1020 is inserted through handle 1056 and is positioned coaxially within outer guide catheter 1000 . In this embodiment, the handles 1056 , 1057 are not linked together as shown in the embodiment illustrated in FIG. 48 . It may be appreciated that such handles 1056 , 1057 may alternatively be connected by external connecting rods, bars or plates or by an additional external stabilizing base. An embodiment of a stabilizing base will be described in a later section. Referring back to FIG. 56 , interventional catheter is inserted through handle 1057 and is positioned coaxially within inner guide catheter 1020 and outer guide catheter 1000 .
[0266] Each handle 1056 , 1057 includes two steering knobs 1300 a , 1300 b emerging from a handle housing 1302 for manipulation by a user. Steering knobs 1300 a are disposed on a side of the housing 1302 and steering knobs 1300 b are disposed on a face of the housing 1302 . However, it may be appreciated that such placement may vary based on a variety of factors including type of steering mechanism, size and shape of handle, type and arrangement of parts within handle, and ergonomics to name a few.
[0267] FIG. 57 illustrates the handles 1056 , 1057 of FIG. 56 with a portion of the housing 1302 removed to reveal the assemblies of the handles. Each knob 1300 a , 1300 b controls a steering mechanism which is used to form a curvature in the attached catheter. Each steering mechanism includes a hard stop gear assembly 1304 and a friction assembly 1306 . Tension is applied to one or more pullwires by action of the hard stop gear assembly to form a curve in a catheter. Tension is maintained by the friction assembly. When tension is released from the one or more pullwires the catheter returns to a straightened position.
[0268] FIG. 58 illustrates steering mechanisms within a handle wherein the housing 1302 is removed for clarity. Here, steering knob 1300 a is attached to a hard stop gear assembly 1304 and a friction assembly (not in view) and steering knob 1300 b is attached to a separate hard stop gear assembly 1304 and friction assembly 1306 . Steering knob 1300 a is attached to a knob post 1318 which passes through a base 1308 , terminating in a knob gear wheel 1310 . The knob gear wheel 1310 actuates the hard stop gear assembly 1304 , thereby applying tension to one or more pullwires 1120 .
[0269] The knob gear wheel 1310 is a toothed wheel that engages a disk gear wheel 1312 . Rotation of the steering knob 1300 a rotates the knob post 1318 and knob gear wheel 1310 which in turn rotates the disk gear wheel 1312 . Rotation of the disk gear wheel 1312 applies tension to one or more pullwires extending through the attached catheter, in this example the outer guiding catheter 1000 . As shown, the outer guiding catheter 1000 passes through the base 1308 , wherein one or more pullwires 1120 extending through the catheter 1000 are attached to the disk 1314 . Such attachment is schematically illustrated in FIG. 59 . Catheter 1000 is shown passing through base 1308 . A pullwire 1120 passing through a steering lumen 1162 in the catheter 1000 emerges from the wall of the catheter 1000 , passes through an aperture 1320 in the disk 1314 and is attached to an anchor peg 1316 on the disk 1314 . Rotation of the disk 1314 (indicated by arrow 1328 ) around disk post 1315 by action of the disk gear wheel 1312 , applies tension to the pullwire 1120 by drawing the pullwire 1120 through the aperture 1320 and wrapping the pullwire 1120 around the disk 1314 as it rotates. Additional rotation of the disk 1314 applies increasing tension to the pullwire 1120 . To limit the amount of tension applied to the pullwire 1120 , to limit curvature of the catheter and/or to avoid possible breakage of the pullwire 1120 , the rotation of the disk 1314 may be restricted by hard stop peg 1322 which is attached to the disk 1314 and extends into the base 1308 .
[0270] FIGS. 60A-60B illustrate how the hard stop peg 1322 is used to restrict rotation of disk 1314 . FIGS. 60A-59B provide a top view, wherein the disk 1314 is disposed on the base 1308 . The anchor peg 1316 is shown with the pullwire 1120 thereattached. A groove 1326 is formed in the base 1308 beneath the disk 1314 and forms an arc shape. The hard stop peg 1322 extends from the disk 1314 into the groove 1326 in the base 1308 . Referring now to FIG. 60B , rotation of the disk 1314 around knob post 1318 , indicated by arrow 1330 , draws the pullwire 1120 through the aperture 1320 as previously described, wrapping the pullwire 1120 around the disk 1314 . As the disk 1314 rotates, the hard stop peg 1322 follows along the groove 1326 , as shown. The disk 1314 continues rotating until the hard stop peg 1322 reaches a hard stop 1324 . The hard stop 1324 is positioned in the groove 1326 and prevents further passage of the hard stop peg 1322 . Thus, disk 1314 rotation may be restricted to any degree of rotation less than or equal to 360 degrees by positioning of the hard stop 1324 .
[0271] In some instances, it is desired to restrict rotation of the disk 1314 to a degree of rotation which is more than 360 degrees. This may be achieved with another embodiment of the hard stop gear assembly 1304 . Referring now to FIGS. 61A-61B , a portion of such a hard stop gear assembly 1304 is shown. FIG. 61A illustrates the base 1308 and the disk post 1315 positioned therethrough. Also shown in the base 1308 is an aperture 1334 through which the knob post 1318 , knob gear wheel 1310 and friction assembly 1306 pass, and a passageway 1336 through which the catheter 1000 passes. In this embodiment of the hard stop gear assembly 1304 , a groove 1326 is also present in an arc shape around the disk post 1315 , however a ball 1332 is positioned in the groove 1326 rather than a hard stop peg 1322 . Disk 1314 is positioned over the groove 1326 and the ball 1332 as shown in FIG. 61B . The disk 1314 , illustrated in FIG. 61C , has a groove 1356 in its surface which is positioned adjacent to the base 1308 , the groove 1356 having an arc shape similar to the groove 1326 in the base 1308 . The ball 1332 is not fixedly attached to the base 1308 or the disk 1314 and is therefore free to move along the channel formed by the groove 1326 in the base 1308 and the groove in the disk 1314 .
[0272] FIGS. 62A-62F illustrate how rotation of the disk 1314 may be restricted by the ball 1332 to a degree of rotation which is more than 360 degrees. FIGS. 62A-62F illustrate the groove 1326 in the base 1308 wherein the groove 1326 has an arc shape around disk post 1315 . The groove 1326 does not form a complete circle; a first groove end 1350 a and a second groove end 1350 b form a wall which prevent passage of the ball 1332 . It may be appreciated that the groove ends 1350 a , 1350 b may be any distance apart, shortening the length of the groove 1326 by any amount, and allowing the ball 1332 movement, and hence catheter deflection, to be adjusted to any desired amount. To begin, referring to FIG. 62A , the ball 1332 is positioned within the groove 1326 near the first groove end 1350 a . The disk 1314 has a matching groove 1352 (shape illustrated in dashed line) including a first groove end 1354 a and a second groove end 1354 b . The disk 1314 is positioned over the ball 1332 so that the ball 1332 is near the second groove end 1354 b.
[0273] Referring now to FIG. 62B , the disk 1314 may be rotated while the ball 1332 remains in place. Here, the disk 1314 has rotated 90 degrees, as indicated by arrow 36000 and the position of the groove ends 1354 a , 1354 b . Referring now to FIG. 62C , the disk 1314 may be further rotated while the ball 1332 remains in place. Here, the disk 1314 has rotated 270 degrees, as indicated by arrow 36000 and the position of the groove ends 1354 a , 1354 b . The disk 1314 may continue rotating to 360 degrees, as shown in FIG. 62D , indicated by arrow 36000 . Here, the first groove end 1354 a in the disk 1314 has contacted the ball 1332 and pushes the ball 1332 along groove 1326 in the base. Referring now to FIG. 62E , the disk 1314 may be further rotated while the ball 1332 is pushed along the groove 1326 in the base 1308 by the first groove end 1354 a in the disk 1314 . Here, the disk 1314 is shown to have rotated 540 degrees. Referring to FIG. 62F , the disk 1314 rotates until the ball 1332 reaches the second groove end 1350 b of the base 1308 , providing a hard stop. In this position, the ball 1332 is held between the first groove end 1354 a of the disk 1314 and the second groove end 1350 b of the base 1308 and further rotation of the disk 1314 is prevented. Thus, the disk 1314 was rotated approximately 660 degrees in this example. Any maximum degree of rotation may be set by positioning of groove ends 1350 a , 1350 b and/or groove ends 1354 a , 1354 b . Additionally, in some embodiments, rotation can be limited by adding more than one ball 1332 to the groove 1326 , for example, two, three, four, five, six, seven, eight, nine, ten or more balls may be used to limit travel and hence curvature.
[0274] It may be appreciated that one or more pullwires 1120 are attached to the disk 1314 in a manner similar to that illustrated in FIG. 59 . Therefore, as the disk 1314 rotates, around disk post 1315 by action of the disk gear wheel 1312 , tension is applied to the pullwire 1120 by drawing the pullwire 1120 through the aperture 1320 and wrapping the pullwire 1120 around the disk 1314 as it rotates. Additional rotation of the disk 1314 applies increasing tension to the pullwire 1120 . Restriction of rotation as described above limits the amount of tension applied to the pullwire 1120 , to limit curvature of the catheter and/or to avoid possible breakage of the pullwire 1120 .
[0275] As mentioned, each steering mechanism includes at least a hard stop gear assembly 1304 and a friction assembly 1306 . As described above, tension is applied to one or more pullwires by action of the hard stop gear assembly to form a curve in a catheter. Tension is maintained by the friction assembly. FIG. 63 illustrates an embodiment of a friction assembly 1306 . The friction assembly 1306 essentially holds a steering knob, in this example steering knob 1300 b , and the associated knob post 1318 in a rotated position. Here, rotation of the knob 1300 b and post 1318 rotates attached knob gear wheel 1310 . The knob gear wheel 1310 actuates the hard stop gear assembly 1304 , thereby applying tension to one or more pullwires 1120 . The knob gear wheel 1310 is a toothed wheel that engages a disk gear wheel 1312 . Rotation of the steering knob 1300 b rotates the knob post 1318 and knob gear wheel 1310 which in turn rotates the disk gear wheel 1312 . Rotation of the disk gear wheel 1312 applies tension to one or more pullwires extending through the attached catheter, in this example the outer guiding catheter 1000 .
[0276] The steering knob 1300 b and knob post 1318 are held in a rotated position by friction provided by a frictional pad 1370 . The frictional pad 1370 is positioned between ring 1372 attached to the knob post 1318 and a plate 1374 attached to the base 1308 . The knob post 1318 extends from the knob 1300 b through the ring 1372 , the frictional pad 1370 and then the plate 1374 . The plate 1374 has internal threads which mate with threads on the knob post 1318 . As the knob post 1318 rotates, the threads on the post 1318 advance through the threads on the plate 1374 . This draws the ring 1372 closer to the plate 1374 , compressing the frictional pad 1370 therebetween. Frictional pad 1370 may be comprised of any O-ring or sheet material with desirable frictional and compressibility characteristics, such as silicone rubber, natural rubber or synthetic rubbers, to name a few. In preferred embodiments, an EPDM rubber O-ring is used. Reverse rotation of the knob post 1318 is resisted by friction of the frictional pad 1370 against the ring 1372 . The higher the compression of the frictional pad 1370 the stronger the frictional hold. Therefore, as the steering knob 1300 b is rotated and increasing amounts of tension are applied to the pullwires 1120 , increasing amounts of friction are applied to the ring 1372 to hold the knob 1300 b in place.
[0277] Manual reverse rotation of the steering knob 1300 b releases tension on the pullwires 1120 and draws the ring 1372 away from the plate 1374 thereby reducing the frictional load. When tension is released from the pullwires 1120 the catheter 1000 returns toward a straightened position.
[0278] It may be appreciated that each handle 1056 , 1057 includes a steering mechanism for each curve to be formed in the attached catheter. Thus, as shown in FIG. 57 , handle 1056 includes a steering mechanism to form the primary curve 1100 in outer guiding catheter 1000 and a steering mechanism to form the additional curve 1110 . Likewise, handle 1057 includes a steering mechanism to form the secondary curve 1104 in inner guiding catheter 1020 and a steering mechanism to form the angle theta 1070 .
[0279] Some curves, such as the primary curve 1100 , secondary curve 1104 and additional curve 1110 each typically vary in curvature between a straight configuration and a curved configuration in a single direction. Such movement may be achieved with single set of a hard stop gear assembly 1304 and a friction assembly 1306 . However, other curves, such as the angle theta 1070 , may be formed in two directions as shown in FIGS. 49C-49D . Such movement is achieved with two sets of the hard stop gear assembly 1304 and the friction assembly 1306 , each set controlling curvature in a single direction.
[0280] FIG. 63 illustrates the presence of an additional set of the friction assembly 1306 ′. One or more pullwires 1120 ′, such as an opposing set as illustrated in FIG. 52D , extending within the wall of the catheter 1000 are attached to the disk 1314 ′ in the same manner as pullwires 1120 are attached to disk 1314 . The disks 1314 , 1314 ′ are arranged so that rotation of steering knob 1300 b in one direction applies tension to the pullwires 1120 via disk 1314 and rotation of steering knob 1300 b in the opposite direction applies tension to the pullwires 1120 ′ via disk 1314 ′. Likewise, the additional friction assembly 1306 ′ is shown having a ring 1372 ′ attached to the knob post 1318 and a frictional pad 1370 ′ disposed between the ring 1372 ′ and the opposite side of the plate 1374 . Therefore, as rotation of the steering knob 1300 b in the opposite direction applies tension to the pullwires 1120 ′ via disk 1314 ′, the frictional pad 1370 ′ applies tension to the ring 1372 ′ holding the knob post 1318 ′ in place.
[0281] It may be appreciated that various other mechanisms may be used for tensioning and holding pullwires 1120 in place. Example mechanisms that may alternatively be used include clutches, ratchets, levers, knobs, rack and pinions, and deformable handles, to name a few.
[0282] F. Interventional System
[0283] FIG. 64 illustrates an embodiment of an interventional system 3 of the present invention. An embodiment of the multi-catheter guiding system 1 of the present invention is shown comprising an outer guide catheter 1000 , having a proximal end 1014 and a distal end 1016 , and an inner guide catheter 1020 , having a proximal end 1024 and a distal end 1026 , wherein the inner guide catheter 1020 is positioned coaxially within the outer guide catheter 1000 , as shown. In addition, a hemostatic valve 1090 is disposed within handle 1056 or external to handle 1056 as shown to provide leak-free sealing with or without the inner guide catheter 1020 in place. The valve 1090 also prevents back bleeding and reduces the possibility of air introduction when inserting the inner guide catheter 1020 through the outer guide catheter 1000 . An example of a hemostatic valve 1090 is illustrated in FIG. 64A , however any suitable valve or hemostatic valve may be used to provide similar functions. In FIG. 64A , the valve 1090 has a first end 1091 , a second end 1092 and a lumen 1093 therethrough. The inner wall of lumen 1093 is preferably tapered toward end 1091 and may further include a plurality of tapered axial channels configured to receive the protrusions 1400 on the inner guide catheter 1020 . The first end 1091 is attached to the outer guide catheter 1000 and the second end 1092 is free. Referring now back to FIG. 64 , the distal ends 1016 , 1026 of catheters 1000 , 1020 , respectively, are sized to be passable to a body cavity, typically through a body lumen such as a vascular lumen.
[0284] To assist in inserting the fixation device 14 through a hemostatic valve 1090 , a fixation device introducer may be used. For example, when the fixation device 14 is loaded on a delivery catheter 300 and an inner guide catheter 1020 , insertion of the fixation device 14 , delivery catheter 300 and inner guide catheter 1020 through an outer guide catheter 1000 involves passing the fixation device 14 through a hemostatic valve 1090 on the outer guide catheter 1000 . To reduce any trauma to the fixation device 14 by the hemostatic valve 1090 , a fixation device introducer may be used. An embodiment of a fixation device introducer 1420 is illustrated in FIG. 64B . The introducer 1420 includes a loading body 1422 and an insertion endpiece 1424 . The fixation device 14 is loaded into the loading body 1422 and into the insertion endpiece 1424 to approximately the dashed line 1428 . The insertion endpiece 1424 has a split end creating individual split sections 1430 , in this embodiment, four split sections 1430 . By compressing the split sections 1430 , the endpiece 1424 forms a taper. Such a taper is then inserted through a hemostatic valve 1090 , so that the insertion endpiece 1424 creates a smooth passageway through the valve for the fixation device 14 . Once the insertion endpiece 1424 is inserted through the valve 1090 , the fixation device 14 , and attached delivery catheter 300 and inner guide catheter 1020 , may then be advanced through the fixation device introducer 1420 . The fixation device introducer 1420 also includes a hemostatic valve within the loading body 1422 to prevent any backbleeding or leakage through the introducer 1420 .
[0285] Manipulation of the guide catheters 1000 , 1020 is achieved with the use of handles 1056 , 1057 attached to the proximal ends of the catheters 1000 , 1020 . As shown, handle 1056 is attached to the proximal end 1014 of outer guide catheter 1000 and handle 1057 is attached to the proximal end 1024 of inner guide catheter 1020 . Inner guide catheter 1020 is inserted through handle 1056 and is positioned coaxially within outer guide catheter 1000 .
[0286] An embodiment of the delivery catheter 300 of the present invention is inserted through handle 1057 and is positioned coaxially within inner guide catheter 1020 and outer guide catheter 1000 . Therefore, a hemostatic valve 1090 is disposed within handle 1057 or external to handle 1057 as shown to provide leak-free sealing with or without the delivery catheter 300 in place. The valve 1090 functions as described above. The delivery catheter 300 includes a shaft 302 , having a proximal end 322 and a distal end 324 , and a handle 304 attached to the proximal end 322 . A fixation device 14 is removably coupled to the distal end 324 for delivery to a site within the body.
[0287] The outer guide catheter 1000 and/or the inner guide catheter 1020 are precurved and/or have steering mechanisms to position the distal ends 1016 , 1026 in desired directions. Precurvature or steering of the outer guide catheter 1000 directs the distal end 1016 in a first direction to create a primary curve while precurvature and/or steering of the inner guide catheter 1020 directs distal end 1026 in a second direction, differing from the first, to create a secondary curve. Together, the primary and secondary curves form a compound curve. Advancement of the delivery catheter 300 through the coaxial guide catheters 1000 , 1020 guides the delivery catheter 300 through the compound curve toward a desired direction, usually in a direction which will position the fixation device 14 in a desired location within the body.
[0288] FIG. 65 illustrates portions of another embodiment of an interventional system 3 of the present invention. Handles 1056 , 1057 of the multi-catheter guiding system 1 of the present invention are shown. Each handle 1056 , 1057 includes a set of steering knobs 1300 a , 1300 b , as shown. Manipulation of the guide catheters 1000 , 1020 is achieved with the use of the steering knobs 1300 a , 1300 b attached to the proximal ends of the catheters 1000 , 1020 . Handle 304 of the delivery catheter 300 is also shown, including the proximal element line handle 312 , the lock line handle 310 , the actuator rod control 314 and the actuator rod handle 316 , among other features. The handle 304 is supported by the support base 306 which is connected to the handle 1057 .
[0289] It may be appreciated the above described systems 3 are not intended to limit the scope of the present invention. The systems 3 may include any or all of the components of the described invention. In addition, the multi-catheter guiding system 1 of the present invention may be used to introduce other delivery catheters, interventional catheters or other devices. Likewise, the delivery catheter 300 may be introduced through other introducers or guiding systems. Also, the delivery catheter 300 may be used to deliver other types of devices to a target location within the body, including endoscopic staplers, devices for electrophysiology mapping or ablation, septal defect repair devices, heart valves, annuloplasty rings and others.
[0290] In addition, many of the components of the system 3 may include one or more hydrophilic coatings. Hydrophilic coatings become slippery when wet, eliminate the need for separate lubricants. Thus, such coatings may be present on the multi-catheter guiding system, delivery catheter, and fixation device, including the proximal elements and distal elements, to name a few.
[0291] Further, the system 3 may be supported by an external stabilizer base 1440 , an embodiment of which is illustrated in FIG. 66 . Stabilizer base 1440 maintains the relative positions of the outer guide, inner guide and delivery catheter during a procedure. In this embodiment, the base 1440 comprises a platform 1442 having a planar shape for positioning on or against a flat surface, such as a table or benchtop. The base 1440 further includes a pair of handle holders 1444 , 1448 , each attached to the platform 1442 and extending upwardly from the platform 1442 , either angularly or perpendicularly. Handle holder 1444 includes a notch 1446 for holding the outer guiding catheter 1000 , as illustrated in FIG. 67 , thereby supporting the handle 1056 . FIG. 67 shows the handle 1056 attached to the outer guiding catheter 1000 positioned so that the proximal end 1014 of the outer guiding catheter 1000 rests in the notch 1446 . Referring back to FIG. 66 , handle holder 1448 includes an elongate portion 1452 having a trough 1450 and a hooked end 1454 . As shown in FIG. 68 , handle 1057 rests on the elongate portion 1452 and the handle 304 rests on hooked end 1454 so that the inner guiding catheter 1020 extends from the handle 1057 to the handle 1056 and continues on within outer guiding catheter 1000 . The handle 304 is additionally supported by support base 306 , as shown.
[0292] It may be appreciated that the stabilizer base 1440 may take a variety of forms and may include differences in structural design to accommodate various types, shapes, arrangements and numbers of handles.
[0293] G. Kits
[0294] Referring now to FIG. 69 , kits 1500 according to the present invention comprise any of the components described in relation to the present invention. The kits 1500 may include any of the components described above, such as the outer guide catheter 1000 including handle 1056 , the inner guide catheter 1020 including handle 1057 , the delivery catheter 300 and the fixation device 14 and instructions for use IFU. Optionally, any of the kits may further include any other system components described above, such as various interventional tools 1040 , or components associated with positioning a device in a body lumen, such as a guidewire 1202 , dilator 1206 or needle 1204 . The instructions for use IFU will set forth any of the methods as described above, and all kit components will usually be packaged together in a pouch 1505 or other conventional medical device packaging. Usually, those kit components which will be used in performing the procedure on the patient will be sterilized and maintained within the kit. Optionally, separate pouches, bags, trays or other packaging may be provided within a larger package, where the smaller packs may be opened separately to separately maintain the components in a sterile fashion.
[0295] While the foregoing is a complete description of the preferred embodiments of the invention, various alternatives, substitutions, additions, modifications, and equivalents are possible without departing from the scope of the invention. For example, in many of the above-described embodiments, the invention is described in the context of approaching a valve structure from the upstream side—that is, the atrial side in the case of a mitral valve. It should be understood that any of the foregoing embodiments may be utilized in other approaches as well, including from the ventricular or downstream side of the valve, as well as using surgical approaches through a wall of the heart. Moreover, the invention may be used in the treatment of a variety of other tissue structures besides heart valves, and will find usefulness in a variety of tissue approximation, attachment, closure, clamping and ligation applications, some endovascular, some endoscopic, and some open surgical.
[0296] Again, although the foregoing invention has been described in some detail by way of illustration and example, for purposes of clarity of understanding, it will be obvious that various alternatives, modifications and equivalents may be used and the above description should not be taken as limiting in scope of the invention which is defined by the appended claims. | The invention provides devices, systems and methods for tissue approximation and repair at treatment sites. The devices, systems and methods of the invention will find use in a variety of therapeutic procedures, including endovascular, minimally-invasive, and open surgical procedures, and can be used in various anatomical regions, including the abdomen, thorax, cardiovascular system, heart, intestinal tract, stomach, urinary tract, bladder, lung, and other organs, vessels, and tissues. The invention is particularly useful in those procedures requiring minimally-invasive or endovascular access to remote tissue locations, where the instruments utilized must negotiate long, narrow, and tortuous pathways to the treatment site. In addition, many of the devices and systems of the invention are adapted to be reversible and removable from the patient at any point without interference with or trauma to internal tissues. | 0 |
REFERENCE TO RELATED APPLICATION
This application is a continuation-in-part of application Ser. No. 397,889, filed Sept. 17, 1973, now abandoned.
BACKGROUND OF THE INVENTION
This invention relates to apparatus for electrocoating. The apparatus, according to this invention, is particularly adapted to the electrocoating of nestable objects such as can ends. More specifically, the invention is particularly adapted for "post repair" of ends.
In the formation of container ends for packaging beer or other carbonated beverages, it is necessary to have the internal surfaces, which are exposed to the product, protected from environmental product attack. In the formation of such container ends, a blank flat sheet material is normally coated by applying a base coat with a roller or other device onto both surfaces of the metal stock prior to the fabrication of the container end. Flat blanks are then cut from the stock and converted into container ends which include a peripheral flange that is utilized for double seaming the end to a container body. In addition, for beer and carbonated beverage products, the container end also has a tear strip formed therein with a tab attached to the tear strip.
During the conversion of the flat blank into the finished end, it is virtually impossible to prevent the removal of some of the coating from certain areas, such as the areas where the frangible connection is produced between the tear strip and the remainder of the end panel. This may result in bare metal spots or uncoated surfaces, on the end, particularly the internal surface that is ultimately exposed to the product. Thus, manufacturers normally apply a subsequent coating to at least the exposed bare metal areas or surfaces of the container end, which is commonly termed "post repair" of the ends.
For years it has been customary to spray a top coat on the interior surface of the fabricated end to seal any scratches, breaks or discontinuities that are produced in the coating during the conversion from the flat blank to the finished end. While this has been found to be an acceptable practice, there are certain shortcomings in utilizing spray coating. One of these shortcomings is the fact that the entire surface must be recoated to insure that all bare spots are covered, which results in wasting coating material in areas where no additional coating is necessary. Another shortcoming is that the spray coating usually incorporates solvents which are dangerous to inhale and must be removed by heating the end.
While the electrodeposition of resinous materials on metal surfaces has been known and proposed for can bodies (see for example, U.S. Pat. Nos. 3,647,675; 3,694,336 and 3,801,485), to the best of applicant's knowledge a successful commercial process for coating can ends for use with beer and carbonated beverages has heretofore not been developed.
There are several problems inherent in any attempt to electrocoat such ends and particularly the "post repair" of coated ends. For example, in order to completely coat the ends, the electrolytic coating solution must be in contact with all surface areas to be coated. Therefore, a means must be devised to move the ends through the coating area which will allow for such full contact. Furthermore, substantial build-up of electrocoated resin on the metallic surfaces making electrical contact with the end should be avoided; otherwise, electrocoating must be interrupted periodically while such surfaces are cleaned. Another problem is encountered when can ends having an easy open end feature are to be electrocoated. These ends generally feature pull tabs that are held in place by a rivet integrally formed in the end, the exposed end of which is located in a recessed area in the bottom surface of the end. Achieving a uniform coating of a rivet-containing end with resin, therefore, has proven to be especially difficult.
A further problem in "post repair" coating of ends is the difficulty in producing metal-to-metal contact between the coated end and an energy source which is necessary for proper electrocoating.
SUMMARY OF THE INVENTION
Accordingly, these difficulties are minimized or eliminated by utilizing a hanger which, first, engages the can end only in areas thereof which are not to be electrocoated; secondly, does not interfere with the flow of electrolytic solution around the ends; thirdly, minimizes resin build-up on the hanger by breaking the electrical connection to the metallic end contact where no end is being held by the hanger; and fourthly, produces excellent electrical contact between the end and the supporting hanger. Furthermore, this hanger, when used in combination with other features of this invention, produces a uniformly coated easy open can end and permits the electrocoating operation itself to be substantially continuous.
Further details, features and advantages of this invention will become apparent from the following description thereof when read in conjunction with the accompanying drawings, in which:
FIG. 1 is a front elevation of the apparatus for electrocoating can ends constructed in accordance with this invention;
FIG. 2 is a partial front view facing into the portion of the apparatus into which the can ends are fed in stacked relation and individually introduced to the hanger;
FIG. 3 is a plan view of the apparatus shown in FIG. 2;
FIG. 4 is an axial cross-sectional view taken along line 4--4 of FIG. 2;
FIG. 5 is a detailed top view of an endless chain for conveying hangers with the hangers attached;
FIGS. 6a and 6b are front views of different embodiments of the hanger of this invention;
FIG. 7 is a front view of the cams effecting opening of the hanger for can end insertion;
FIG. 8 is a front view showing the path of the hanger conveyor just after insertion of the ends;
FIG. 9 is a plan view of the structure shown in FIG. 8;
FIG. 10 is a frontal view of the spraying station from which a stream of electrolytic solution is directed toward the area of the rivet head;
FIG. 11 is a view transverse to the direction of travel of the conveyor showing the spraying station of FIG. 10;
FIG. 12 is a vertical transverse section taken along line 12--12 of FIG. 1 showing the passage of the can ends through the electrolyte in the basin;
FIG. 13 is a front view, partially in section, of the basin showing means for maintaining an essentially level laminar flow of electrolyte;
FIG. 14 is a plan view of the basin;
FIG. 15 is a side elevation showing the mechanism for transferring the ends from the hangers to oven conveying screws;
FIG. 16 is an end view of the apparatus shown in FIG. 15;
FIG. 17 is a cross-sectional view of the mechanism for carrying ends from a guide wheel to a screw conveyor which conveys the ends through an oven;
FIG. 18 is a similar cross-sectional view illustrating the position of the mechanism immediately prior to feeding of an end into the screw conveyor;
FIG. 19 is a cross-sectional plan view showing the detent mechanism as it is attached to the chain in the position illustrated in FIG. 18;
FIG. 20 is an end view of the cam which positions the detent mechanism for end transporting;
FIG. 21 is a transverse sectional view illustrating ends as they are being conveyed by parallel screws;
FIG. 22 is a side view of the screw used to carry the ends through the oven.
FIG. 23 is a top plan view of a further modified form of hanger structure for supporting the can end;
FIG. 24 is a side elevation view of the hanger shown in FIG. 23;
FIG. 25 is an end view of the hanger shown in FIG. 23; and
FIG. 26 is an enlarged fragmentary sectional view as viewed along line 26--26 of FIG. 24.
DETAILED DESCRIPTION
Prior to a detailed description of the invention, a brief reference to FIG. 1 will provide a broad summary of the arrangement and operation of the parts employed.
Stacked can ends E are conveyed and inserted in the hangers 1 by means of end feeding and marrying mechanism 2 which is comprised of end feeding mechanism 20, studded chain 32 and cams 7. The hangers 1, attached to chain 34, are then conveyed into the electrocoating basin 11 where the electrocoating operation is performed. The coated ends are conveyed through a rinse tank 112 containing deionized water then past a hot air blower 114 and removed from the hanger 1 by cams 7. After removal the ends are loaded on an endless screw 130 for conveying through curing oven 200.
Having generally described the overall arrangement and operation of the apparatus, the specific parts which make up the apparatus will be described in detail.
The first part of the apparatus is the end feeding and marrying mechanism 2 illustrated in FIG. 1.
Can ends are initially placed in the feeding mechanism 20 by stacking them in the end feed tube 12 as illustrated in FIGS. 2, 3, and 4. The end feed tube 12 is held in place by attachment rings 14 which are bolted to back plate 28, the back plate being bolted to support members 10. The support members are attached to the frame 26 as shown in FIG. 2. Individual ends E are passed into contact with worm gear 24 by fingers 16 which are actuated by air cylinder 18. Vacuum means 22 are provided to urge the individual ends against the studded chain 32 shown in FIG. 1. As shown in FIG. 1, the ends are maintained in position by means of track guide 9 as they are raised by the studded chain 32 which is propelled by sprocket 17. The ends are propelled around the arc prescribed by sprocket 17 and are allowed to drop parallel to hangers 1 as the studded chain 32 completes its path around the sprocket 17.
The hanger and conveying apparatus 4, as represented in FIG. 1, includes the hanger 1 and its conveying means. The hanger 1 is attached to chain 34 by mounting piece 37. A series of sprockets 64 mounted on shafts 60 are supported by pillow blocks 62 which rest upon frame 100, as shown in detail in FIGS. 8 and 9, are used to direct and support the chains. As shown in FIG. 1, drive sprocket 63 is powered by motor means 110 which is used to move the chain and hanger combination through the path indicated. Chain guards 69, as illustrated in FIG. 9, are used to minimize transverse movement of the chain and are mounted upon the frame, spacedly, along the path of the chain 34.
Before continuing with the detailed description of the remainder of the apparatus, a detailed description of the hangers is provided.
FIG. 6a provides a view of one embodiment of the hanger. The hanger brushes or contact elements 36 are designed to be in electrically conductive contact with the cathode track 33 shown in FIG. 5. The springs 38 inside brushes 36 are in electrically conductive contact with the leaf contact spring 39 which is attached by screw 40 to the electrically conductive body 50. Nuts 44 engage headless screw 40 to mount the brushes 36 on the hanger body 50. When an end is present between body 50 and jaw 51, as illustrated in FIG. 6a, the release spring or bearing means 54 is depressed in spring cavity 41, and the electrically conductive jaw 51, having flange 53, is in contact with the contact spring 39 and, therefore, in electrically conductive contact with the brushes 36. Of course, it will be appreciated that the lower edge of the internal surface of jaw 53 is in direct contact with an uncoated edge of the end. This uncoated edge is developed when the flat blank is severed from the coated sheet stock. This arrangement produces excellent metal-to-metal contact between jaw 51 and end E.
When in the coating basin 11 the brushes are in electrically conductive contact with the cathode tracks 33 and current flows through the brushes 36, contact spring 39, jaw 51, and the uncoated cut edge to the end E.
The can end, when in place rests against positioning members 56 at its outer extremity and is maintained in position by position screw 58. The positioning members and position screw insure that only the lip of the can end will be gripped by the jaw. Wear plate 52 is provided for contact with the support cam. When an end is not held between the electrically conductive jaw 51 and the body extension 50 forming the support jaw, the release spring 54 pushes the jaw 51 around the pivot point 48 to a first position with respect to body 50 away from contact or in spaced relation with respect to contact leaf spring 39 as illustrated in FIG. 6b.
FIG. 6b shows an alternative configuration of the hanger. This figure illustrates an extension of the body 50 to form an extended jaw 57 of the same shape as the can end itself. The extended jaw has, affixed to its circumference, an O-ring sealing element 59 designed to abut the can end at its periphery and seal it from electrocoating. Depending upon the electrocoating conditions and the particular choice of resins, it may be desirable to prevent electrocoating of the top of the can end. If the top is coated, a film might form which, if an easy open end is used, could bind the tab to the surface of the top making the tab more difficult to remove. The configuration of the hanger shown in FIG. 6b is preferred in such circumstances.
FIGS. 23 through 26 show a further modified configuration for hanger 1. This particular hanger structure is more specifically adapted for post repair of ends which are formed from a stock material that is coated on both sides. The hanger structure shown in FIGS. 23 through 26 consists of a hanger body 200 which is connected to the endless chain 34 through a suitable bracket 202. Hanger body 200 has a jaw 204 pivotally supported by pin 206 and biased to a closed position by a spring 208 supported in a recess 210 on the body.
Hanger body 200 also has means intermediate opposite end for engaging cathode track 33. This means is most clearly shown in FIG. 23 and consists of a threaded screw 212 extending through the body and held in a fixed position with respect to body 200 by a pair of locked nuts 214. The respective outer ends of the threaded screw have links 216 pivotally supported thereon intermediate opposite ends by a bolt 218. A pair of rollers 220 are respectively rotatably supported on one end of the links 216 through further screws 222. The opposite ends of the links 216 are interconnected by a spring 224 so that the rollers and links are biased to a first position that will now be described.
The first position for links 216 and rollers 218 is defined by a plate 230 that has opposite ends 232 located in vertical alignment with links 216. Thus, when the rollers are free of engagement with cathode tracks 33, spring 224 will bias the links into engagement with the ends 232 of plate or stop 230. However, if rollers 220 are in engagement with cathode tracks 33, as shown in FIG. 23, the spring 224 aids in maintaining positive contact between rollers 220 and cathode tracks 33 to insure sufficient contact to produce a current flow from cathode tracks to rollers 220. Preferably, a bar 233, having a length greater than plate 230 is positioned next to the plate and extends between the respective pairs of links to guide the links during pivotal movement between positions. Plate 230 and bar 233 may be secured to body 200 by set screw 234.
Thus, when the hanger is between a pair of cathode tracks 33, a current flow will be developed through rollers 220, links 216, screw 212 and main body 200. To insure that there is sufficient current flow to fully energize all portions of the container end E, it is peferable that one screw 218 be directly connected to pivoted jaw 204 through a lead wire 240. The advantages of a direct connection between jaw 204 and links 216 will become more apparent hereafter.
The hanger shown in FIGS. 23-26 also has a cam engaging member 235 on body 200 and a cam engaging member 236 on jaw 204 to move the jaw to an open position. Preferably, cam engaging member 236 is in the form of a cam roller.
Applicant has determined that it is highly advantageous to provide direct metal-to-metal contact between the container ends and at least a portion of the hanger to insure proper electric current flow from cathode track 33 to end E. For this purpose, pivoted jaw 204 has an insert 242 at the lower end thereof which engages one surface of end E. The details of this insert are illustrated in FIG. 26. As shown, insert 242 is substantially U-shaped and has a web portion 244 connected to the lower edge of jaw 204 by a screw 246. A pair of legs 248 on opposite edges of web 244 are directed towards body portion 200. The respective legs have recesses or notches 250 formed therein and the recesses or notches are positioned so as to be in alignment with the peripheral edge 252 of container end E. As in the previous embodiments, positioning pins 260 are utilized to position the ends with respect to body 200.
Insert 242 is formed from a steel which is preferably hardened so that the Brinell hardness of the steel is substantially greater than the Brinell hardness of the metal utilized in forming the end E. Preferably, the insert 242 has a Brinell hardness number which is at least twice the Brinell hardness number of the metal alloy utilized in forming end E. Furthermore, it is desirable that the inner surface of groove 250 be rather sharp to insure that the edge of groove 250 will cut into the edge of container end E, particularly the edge of the peripheral flange thereon.
The use of the insert and the direct metal-to-metal contact between the edge of the insert and the peripheral edge of the end E has been found to greatly enhance the coating characteristics in the normal post repair of the end. Of course, it will be appreciated that the peripheral edge of the container end is devoid of any coating since the original roll coating that was applied to the flat metal stock is applied prior to the severing of the circular blank to form the end. Thus, the cut edge is devoid of any coating.
It has also been found that the above arrangement has an additional advantage in that any coating build-up on the insert 242 will be removed during the penetration of the sharp edge of groove 250 into the metal edge of the container end E which will improve the metal-to-metal contact resulting in greater current conducting capacity from the jaw 204 to the end E.
The above-described hangers are opened as shown in FIG. 7 by means of a set of cams 7 mounted on frame 100. Each cam set 7 consists of cam 31 that provides a cam surface for engaging hanger wear plate 52 or member 235, and a second cam 30 that provides a surface for engaging flange 53 of the electrically conductive jaw 51 or roller 236 of electrically conductive jaw 204. Cam surfaces on cams 30 and 31 are positioned so that conductive jaw 51 or 204 is pivoted to an open position for receiving an end E when the hangers are between the cams. The ends are inserted by means of the can insertion apparatus 2 which, as described above, orients the can ends parallel to and between the open jaws of the hangers as they pass through the cams. As illustrated in FIG. 1, a spring biased pusher plate 13 pushes the can ends firmly into the jaws just prior to the closing of the jaws as they leave the area of the cams 7.
FIGS. 8 and 9 further illustrate the wedding of the ends to the hangers, the path of the hanger and the relationship between the hanger, the cam just after insertion. After the ends are inserted they are carried by the hangers to basin 11.
If the can ends to be electrocoated are of the easy open end type, they are, prior to entering basin 11 preferably directed past a spraying station illustrated in FIGS. 10 and 11. A concentrated stream of electrolytic solution is directed by nozzles 66 at the rivet area R of the easy open ends under sufficient force to break surface tension and prevent air entrapment at the rivet bottom. As is shown in FIG. 11, the nozzles are held in place on the edge of the tank 74 by mounting plate 72 which is attached to the tank edge by bolt 76. Liquid is raised to the atomizer through tube 68 by creating a partial vacuum by means of air valve 70. When the liquid is in spray tube 67 air is forced in through the valve 70 to force the liquid through the atomizing nozzle 66 and wet a surface of the container ends. As is shown in FIG. 10, the atomizing nozzles are mounted in tandem.
The can ends are next conveyed to the electrocoating basin 11 as shown in FIG. 12. The brushes or contact elements 36 or 220 of hanger 1 are in contact with cathodic tracks 33 mounted on frame 100 as they are moved through the basin area. It should be noted that the level of electrolyte in the basin is such that it covers the can end only. The relationship of relative height of solution to the location of the can end is important and the particular one illustrated is preferred, as will be discussed in more detail below. The anodes 86 are attached to anode supports 75 which are mounted upon the basin 11. Separating the anode from the end is an anode guard 88 to prevent accidental contact between the anode and the end. Thumb screws 77 are provided for adjusting the spatial relationship between the anode and the ends as the latter are electrocoated.
If the electrolyte covers the hanger body, it can leave a sticky deposit on the body surface and interfere with the operation of its various parts. The level of electrolyte in the basin is maintained by use of a reservoir and sensing means 140 represented in FIG. 1 in combination with an adjustable weir 80 illustrated in FIGS. 13 and 14. As the hangers pass through the solution, electrolyte is carried out from the supply in the basin. The reservoir and sensing means 140 is designed to maintain the necessary minimum constant level, shown in FIG. 12, where only the ends and a very small portion of hangers 1 are immersed in the liquid solution. Excess solution is spilled out over weir 80 and recirculated through exit port 82 by pipe 83 into inlet tubes 78. As shown in FIG. 14, the inlet tubes 78 are slotted. Electrolyte leaves all the slots under essentially equal pressure to produce an essentially laminar flow which is highly desirable because it aids in producing a uniform continuous coating on the end.
As clearly shown in FIG. 12, there are two cathode tracks 33 for each conveyor 34 and the two cathode tracks, which define fixed cathode track means, are located on opposite sides of the path for hangers 1. Also, cathode tracks 33 are positioned to be between endless conveyors 34 and basin 11. The net effect is that each hanger is supported at one end on conveyor 34 and contact elements 36 or 220, located intermediate opposite ends of hanger body 50 or 200, engage fixed tracks 33, resulting in ends E being a substantially fixed distance from anode 86 as they move through basin 11.
As the hangers leave the basin or trough they pass through a second basin 112 where the ends are sprayed with deionized water to remove any excess solution. They are then subjected to the action of a hot air blower 114 to remove the deionized water and are carried to the hanger release area 6. The hangers are opened and the end released by means of the cam configuration 7 illustrated in FIG. 7 and discussed above in relation to the end insertion procedure. The only difference between the end releasing procedure and the end insertion procedure is that the hangers approach the unloading cams going in an upward, rather than a downward, direction.
As shown in FIG. 15, after the hangers are opened, the ends are engaged by guide wheel 90 turning about guide wheel shaft 91 and conveyed along track guide 94 where they are engaged by ball detents 96 which are carried along endless chain 99 and are turned by sprocket means identical to those used to position the endless chain to which the hangers are attached. This assembly, as also shown in FIG. 16, is supported by the support members 98 and support strut 97 which is affixed to the frame 100.
FIG. 17 shows the position of the ball detent as it initially engages the can ends. As the ends are conveyed upwardly the guide track turns 90 degrees to reorient the position of the ends as shown in FIG. 16. As the ends are raised over the top sprocket the ball detent assumes the position shown in FIG. 18. The ends are then dropped through the hinged area 95 of the track guide 94 onto endless screw 130. The endless screw 130 conveys the ends to and through a drying oven to fully cure the resin. A representation of the type of screw that is desirable for conveying the can ends is shown in FIGS. 21 and 22. FIG. 22 shows the initial pitch, width at the flat of the root and at the crest of the screw as the ends are released to it. It is desirable to correlate unloading the ends so that they are mated to one root width of the screw 130 while rapid curing indicates that the root width of the screw be decreased. As represented in FIG. 21, one more screw than the number of ends is needed to convey the ends through the oven 200.
Meanwhile, as shown in FIG. 20, the ball detents 96 are carried downwardly past the detent cam 102 bolted to support member 106, as illustrated in FIG. 20. This shifts the detents to the position shown in FIG. 17 so that they are able to engage the next group of ends as they are conveyed around the path of endless chain 99.
As can be appreciated from the above description, the present invention provides a unique method and apparatus for the post repair of ends to insure a uniform coating is produced on the surface which comes in contact with the packaged product, such as beer or carbonated beverages. It will be appreciated that, while the invention has been specifically described in connection with the repair of coated ends, the invention has equal applicability for initially coating a metal end that was preformed without any coating thereon. | Apparatus and method for supporting and conveying objects or articles, such as can ends, through an electrolytic solution is disclosed herein. The apparatus consists of an endless conveyor that has a plurality of hangers with the hangers being opened to receive objects and closed to grip the article. Each of the hangers has a fixed body with a jaw on the fixed body biased to a closed position. The hanger also has electrically conductive means for accommodating current flow from a fixed cathode track through the jaw to an object being gripped between the jaw and the body so that the articles are automatically coated when the energized articles are passed through a basin containing the solution and a fixed anode. | 1 |
This is a divisional of application(s) Ser. No. 09/195,512 filed on Nov. 19, 1998 now U.S. Pat. No. 6,069,245 which is a continuation of Ser. No. 08/832,253 filed Apr. 3, 1997 now U.S. Pat. No. 5,902,882.
TECHNICAL FIELD
The present invention is concerned with a novel process for the manufacture of azepines and with intermediates used in this process.
DETAILED DESCRIPTION
The present invention is concerned with a process for the manufacture of azepines of the formula
wherein R 1 and R 2 are independently an acyl residue of an aromatic carboxylic acid.
The compounds of formula I include known, pharmacologically active compounds, for example, balanol (see Int. Patent Application WO 93/03730) and other phosphokinase inhibitors, for example, the compounds described in European Patent Application A-0 663 393. The process in accordance with the invention enables such compounds to be manufactured in a simpler and more economical manner than has been possible with previously known processes.
In the scope of the present invention, acyl residues R 1 and R 2 are selected from the group consisting of benzoic acid; benzoic acid substituted by the group selected from hydroxy, halogen, preferably fluorine, lower-alkyl and lower-alkoxy; benzoyl; and benzoyl substituted by the group selected from fluorine, lower-alkyl and lower-alkoxy. The term “lower” denotes groups with 1-6 C atoms. Compounds of formula I in which R 2 is p-hydroxybenzoyl or p-(2-fluoro-6-hydroxy-3-methoxybenzoyl)benzoyl and R 1 is p-hydroxybenzoyl or 4-hydroxy-3,5-dimethylbenzoyl are preferred. R 4 is an amino protecting group, perferably tert.-butoxycarbonyl.
In one embodiment of the present invention, the novel process for the manufacture of compounds of formula I comprises the catalytic asymmetric hydrogenation of a compound of the formula
wherein R 3 is lower-alkyl and HX is an acid, to a compound of the formula
Examples of acids HX for the acid addition salts of formula II and formula IV are inorganic acids, such as mineral acids, for example HCl, and organic acids, such as sulphonic acids, for example, p-toluenesulphonic acid and methanesulphonic acid.
The catalyst for the asymmetric hydrogenation is a complex of an optically active, preferably atropisomeric, diphosphine ligand with a metal of Group VIII of the periodic system, especially ruthenium. Such catalysts are described, for example, in European Patent Publication A-0 643 052.
As catalysts there come into consideration rhodium-diphosphine complexes of the formulae
(RuL) 2+ (X 0 ) 2 III-a
(RuLX 2 ) 2+ (X 0 ) 2 III-b
(RuLX 1 X 2 ) + X 3 III-c and
RuL(X 4 ) 2 III-d
wherein
X 0 is selected from the group consisting of BF 4 − , ClO 4 − , B(phenyl) 4 − , SbF 6 − , PF 6 − , and Z 1 —SO 3 − ; X 1 is halide; X 2 is benzene, hexamethylbenzene or p-cymene; X 3 is selected from the group consisting of halide, ClO 4 − , B(phenyl) 4 − , SbF 6 − , PF 6 − , Z 1 —SO 3 − and BF 4 − ; X 4 is selected from the group consisting of Z 2 —COO—, Z 3 —SO 3 − , allyl and CH 3 COCH═C(CH 3 )O—; Z 1 is halogenated lower alkyl or halogenated phenyl; Z 2 is selected from the group consisting of lower alkyl, phenyl, halogenated lower alkyl and halogenated phenyl; Z 3 is lower alkyl or phenyl; and L is an optically active, preferably atropiso-meric, diphosphine ligand.
Especially preferred ligands L are
MeOBIPHEP (6,6′-Dimethoxybiphenyl-2,2′-diyl)bis-(diphenylphosphine); BIPHEMP (6,6′-Dimethylbiphenyl-2,2′-diyl)bis-(diphenylphosphine); BINAP ((1,1′-Binaphthyl)-2,2′-diyl)bis-(diphenylphosphin); pTol-BIPHEMP (6,6′-Dimethylbiphenyl-2,2′-diyl)bis(di-(p-tolyl)phosphine); pAn-MeOBIPHEP 6,6′-Dimethoxy-P,P,P′,P′-tetrakis-(4-methoxy-phenyl)-biphenyl-2,2′-bis-phosphine; pDMA-MeOBIPHEP 6,6′-Dimethoxy-P,P,P′,P′-tetrakis-(4-dimethylamino-phenyl)-biphenyl-2,2′-bis-phosphine; pPhenyl-MeOBIPHEP (6,6′-Dimethoxybiphenyl-2,2′-diyl)-bis(bis-(biphenyl)-phosphine); mTol-BIPHEMP (6,6′-Dimethylbiphenyl-2,2′-diyl)bis(di-(m-tolyl)phosphine); Cy 2 -MeOBIPHEP P2, P2-Dicyclohexyl-6,6′-dimethoxy-P2′,P2′-diphenyl-biphenyl-2,2′-bis-phosphine; 2-Furyl 2 -BIPHEMP P,P-Diphenyl-P′,P′-di-2-furyl-(6,6′-di methyl-biphenyl-2,2′-diyl)diphosphine; (3,5-Me,4-MeO)-MeOBIPHEP 6,6′-Dimethoxy-P,P,P′,P′-tetrakis-(dimethyl-4-methoxy-phenyl)-biphenyl-2,2′-bis-phosphine; DiMeOBIPHEP (5,5′,6,6′-Tetramethoxybiphenyl-2,2′-diyl)bis(diphenylphosphine); TriMeOBIPHEP (4,4′,5,5′,6,6′-Hexamethoxybiphenyl-2,2′-diyl)bis(diphenylphosphine); and 2-Furyl-MeOBIPHEP (6,6′-Dimethoxybiphenyl-2,2′-diyl)bis-(di-2-furylphosphine).
These ligands are described in Patent Publications EP 643 052, EP 647 648, EP 582 692, EP 580 336, EP 690 065, EP 643 065, JP 523 9076.
Diacetoxy-ruthenium-[(R)-6,6′-dimethoxybiphenyl-2,2′-diyl]bis(diphenylphosphine [Ru(OAc) 2 (R)-MeOBIPHEP] is an especially preferred catalyst.
The ratio of ruthenium to ligand L in the complexes of formulae II-a to III-d is from about 0.5 mol to about 2 mol, preferably at about 1 mol of ruthenium per mol of ligand. The substrate/catalyst ratio (S/C; mol/mol) is from about 20 to about 30000, preferably from about 100 to about 5000.
The hydrogenation is carried out with the exclusion of oxygen in ethanol under an elevated pressure, for example, at pressures of from about 1 bar to about 100 bar, preferably from about 5 bar to about 70 bar, and at temperatures of from about 0° C. to about 80° C., preferably from about 20° C. to about 50° C.
The compound of formula IV is converted into a carboxylic acid compound of the formula
wherein R 4 is a protecting group,
preferably a tert.-butoxycarbonyl group. The ester group R 3 of the compound of formula IV is saponified using aqueous alkali, for example, sodium hydroxide solution, at room temperature. The carboxylic acid of formula V is then converted by known methods into an acid azide or acid amide containing compound of the formula
wherein A is azide or amino.
Subsequent degradation according to Curtius or Hofmann, yields an oxazolidone compound of the formula.
The oxazolidone of formula VI is hydrolyzed to a compound having the formula
in a manner known per se, for example, using aqueous-alcoholic alkali while heating to 70-90° C.
The hydroxy group and the amino group in the compound of formula VII are then acylated in a manner known per se, for example, by reaction with a reactive derivative of a carboxylic acid R 1 COOH or R 2 COOH, such as a mixed anhydride. When these carboxylic acids contain acylatable groups, such as OH groups, these groups are conveniently intermediately protected. Compounds of formula I in which R 1 and R 2 are different from one another can be obtained, for example, by N-acylating the amino group in the compound of formula VII selectively with 1 equivalent of R 1 COOH and subsequently O-acylating with 1 equivalent of R 2 COOH.
The protecting group R 4 can be removed in a manner known per se from the compound of formula VII. For example, when R 4 is tert.-butoxycarbonyl group, R 4 can be removed by treatment with an acid, such as 2N HCl in a solvent such as ethyl acetate.
Another embodiment of the novel process for the manufacture of compounds of formula I, in accordance with the present invention, comprises microbially reducing a compound of the formula
wherein R 3 is lower alkyl and R 4 is a protecting group, to a compound having the formula
In principal, the reduction is not limited to a specific microorganism. Fungus strains (fungi), especially yeasts, are conveniently used as the microorganisms. An especially preferred microorganism is Hanseniaspora uvarum R 1052, especially the strain deposited on 16.1.1996 at the Deutschen Sammlung von Mikroorganismen und Zellkulturen (DSMZ) under No. DSM 10 496.
The reduction of a compound III to a compound of formula IV can be carried out using intact cell cultures or using enzymes obtained from the microorganisms. The preferred microorganism, Hanseniaspora uvarum R 1052, can be cultivated in aerobic aqueous submersed cultures on usual nutrient substrates which contain carbon and nitrogen sources, for example, glucose or starch, and, respectively, soya meal, yeast extract or peptone, as well as inorganic salts, such as ammonium sulphate, sodium chloride or sodium nitrate. The cultivation can be carried out at temperatures of about 20-35° C., preferably at 27° C., in a pH range of about 3-9, preferably at about pH 5-7.
The compound of formula III is added to the culture of the microorganism in an organic solvent, for example, ethyl acetate.
The course of the reduction can be followed by thin-layer chroma-tography of samples of the reaction medium. In general, the reaction takes about 8-12 hours. The reaction product, the compound of formula VIII, can be separated from the culture solution by extraction with a suitable organic solvent, for example, with ethyl acetate.
In the next reaction step, the compound of formula VIII is saponified, using aqueous alkali, for example, sodium hydroxide solution, at room temperature, to its corresponding carboxylic acid. The carboxylic acid is then converted using known methods into an acid azide or acid amide containing compound of the formula
Subsequent degradation according to Curtius or Hofmann yields an oxazolidone compound of the formula
By alkaline hydrolysis of the oxazolidone IX, for example by using aqueous-alcoholic alkali while heating to 70-90° C., there is obtained a compound of the formula
The hydroxy group and the amino group in the compound of formula X are then acylated in a manner known per se, for example, by reaction with a reactive derivative of a carboxylic acid R 1 COOH or R 2 COOH, such as a mixed anhydride. The compound of formula X is preferably N-acylated with an aromatic carboxylic acid of the formula R 1 COOH to a compound having the formula
The compound of formula XI is then acylated with an aromatic carboxylic acid or a reactive derivative thereof, of the formula R 2 OH, in the presence of triphenylphosphine and diethyl azo-dicarboxylate, to yield a compound having the formula
The protecting group R 4 can be removed in a manner known per se from the compound of formula XII. For example, when R 4 is tert.-butoxycarbonyl group, R 4 can be removed by treatment with an acid, such as 2N HCl in a solvent such as ethyl acetate.
The intermediate compounds of the formulae II, IV, V, VI, VIII, VIIIa, IX, X and XI as well as the compound prepared in Example 12a and, respectively, 17 are novel and are likewise objects of the present invention.
The invention is illustrated in more detail by the following Examples, however is in no manner limited thereby. In these Examples, the abbreviations used have the following significance: “ee” is “enantiomeric excess”, which is defined as percent of R-product minus percent of S-product; “dec.” is “decomposition”; HPLC is high performance liquid chromatography.
EXAMPLE 1
Preparation of Compounds of Formula II and Formula III.
a) A solution of 218.3 g of di-tert-butyl dicarbonate in 250 ml of dichloromethane was added at 20-25° C. while stirring, in the course of 1 hour, to 101.2 g of piperidin-3-ol in 750 ml of dichloromethane. The reaction mixture was stirred at room temperature for a further 2 hours. Thereafter, a solution of 33.6 g of sodium bicarbonate and 11.9 g of potassium bromide in 1000 ml of deionized water was added and the reaction mixture was cooled to −20 C. After the addition of 0.39 g of 2,2,6,6-tetramethyl-piperidine 1-oxide, 560 g of 13.3% aqueous sodium hypochlorite solution were added at 0-5° C. in the course of 80 minutes. After stirring at −2° C. for a further 30 minutes, the excess sodium hypochlorite solution was added at 0-5° C. in the course of 80 minutes. After stirring at −20° C. for a further 30 minutes, the excess sodium hypochlorite was destroyed by the addition of about 10 ml of 38% aqueous sodium bisulphite solution. The reaction mixture was then warmed to 20° C. and the aqueous layer was separated and extracted with 500 ml of dichloromethane. Both organic phases were washed with 500 ml of 10% sodium chloride solution, combined and dried over sodium sulphate. After filtration and removal of the solvent under reduced pressure the oily residue was purified by distillation under reduced pressure which yielded 191.2 g of tert-butyl 3-oxo-piperidine-1-carboxylate as a colourless oil, boiling point 80-82° C./0.01 mbar. b) 99.6 g of the compound obtained in paragraph a) were dissolved in 600 ml of diethyl ether. The solution was cooled to −70° C. and the white suspension was treated simultaneously and dropwise in the course of 1 hour with solutions of 62.0 ml of ethyl diazoacetate in 125 ml of diethyl ether and 69.0 ml of boron trifluoride etherate in 125 ml of diethyl ether, with the internal temperature being held at −70° C. After stirring at −70° C. for a further 1 hour the cooling bath was removed, the reaction mixture was warmed to 0° C. and treated with 375 ml of 10% sodium carbonate solution. The aqueous phase was separated and extracted with 250 ml of diethyl ether. The organic phases were washed with 250 ml of 10% sodium chloride solution, combined and dried over sodium sulphate. The solvent was removed under reduced pressure at 30° C. yielding ethyl 1-(tert-butoxycarbonyl)-4-oxo-azepan-3-carboxylate as a crude product in the form of a yellow oil, which was used in the next step without further purification. c) 147.2 g of the product obtained in paragraph b) were dissolved in 1250 ml of dioxan and seeded with 0.1 g of ethyl 4-oxo-azepan-3-carboxylate hydrobromide. Thereafter, 175 ml of 5.7M. HBr/ethyl acetate were added at room temperature, while stirring, in the course of 25 minutes. After further seeding with 0.1 g of ethyl 4-oxo-azepan-3-carboxylate hydrobromide, the suspension was stirred at room temperature for 5 hours. The crystals were filtered off, washed with ethyl acetate and dried at 50° C. and 25 mbar. The resulting 91.0 g of crude ethyl 4-oxo-azepan-3-carboxylate hydrobromide was dissolved in 1250 ml of 2-butanone while stirring and heating under reflux. The solution was cooled to 65° C. and seeded with 0.1 g of pure ethyl 4-oxo-azepan-3-carboxylate hydrochloride. After cooling to room temperature, the suspension was stirred at room temperature for 1 hour and at 0° C. for 3 hours. The crystals were filtered off, washed with 200 ml of 2-butanone (cooled to −10° C.) and dried at 50° C. and 25 mbar, yielding 68.2 g of white ethyl 4-oxo-azepan-3-carboxylate hydrobromide, melting point 127-130° C. (dec.). d) 59.4 g of the compound obtained in paragraph b) were dissolved in 1000 ml of 1M HCl in dioxan and stirred at room temperature for 24 hours. After a reaction period of 1.5 hours the solution was seeded with about 25 mg of ethyl 4-oxo-azepan-3-carboxylate hydrochloride. The white suspension was filtered, washed with dioxan and dried at 50° C. and 25 mbar, yielding 31.3 g of ethyl 4-oxo-azepan-3-carboxylate hydrochloride in the form of white crystals, which contained about 0.4 mol of dioxan per mol of hydrochloride according to the NMR spectrum. The hydrochloride was recrystallized for further purification and in order to remove the dioxan. 31.3 g of ethyl 4-oxo-azepan-3-carboxylate hydrochloride were dissolved in 600 ml of 2-butanol at 80° C. and the solution was cooled to −20° C. in the course of 2 hours and stirred at −20° C. for 3 hours. The white suspension was filtered, washed with 2-butanol (cooled to −20° C.) and dried at 50° C. and 25 mbar to yield 22.9 g of ethyl 4-oxo-azepan-3-carboxylate hydrochloride in the form of white crystals, melting point 145-148° C. (dec.).
EXAMPLE 2
75.0 g of ethyl 4-oxo-azepan-3-carboxylate hydrochloride and 800 ml of ethanol were introduced into an autoclave. The autoclave was closed and the air was removed therefrom by repeated evacuation to about 0.1 bar and pressurization with argon (7 bar) and hydrogen (40 bar) while stirring. Thereafter, a solution of 226 mg of diacetoxy-rhuthenium (R)-6,6′-dimethoxybiphenyl-2,2-diyl)-bis(diphenylphosphine) in 20 ml of ethanol was fed into the autoclave at 2 bar hydrogen pressure with the exclusion of oxygen. Thereafter, hydrogen pressure was increased to 40 bar and the reaction mixture was hydrogenated while stirring at 30° C. for 19 hours and at 50° C. for 3 hours. Thereafter, the content of the autoclave was washed out with 200 ml of ethanol and the combined solutions were evaporated at 50° C./100 mbar and the brown residue was dried for 2 hours. The residue (75.9 g, consisting of about 80% 3R,4R and 20% 3S,4R isomers) was triturated with 450 ml of tetrahydrofuran at 24° C. for 19 hours and at 16° C. for 1 hour. The crystals were filtered off under suction, washed with tetrahydrofuran and dried to constant weight at 50° C./20 mbar for 3.5 hours. There were obtained 56.3 g of light beige crystals, which were again triturated with 225 ml of tetrahydrofuran as previously described. The crystals were removed by suction filtration and dried, yielding 55.1 g of ethyl (3R,4R)-4-hydroxy-azepan-3-carboxylate hydrobromide in the form of white crystals, which were enantiomerically pure according to HPLC.
EXAMPLE 3
As in Example 2, 23.2 g of ethyl 4-oxo-azepan-3-carboxylate hydrochloride in 90 ml of ethanol were hydrogenated with a solution of 36.1 mg of the ruthenium catalyst in 10 ml of ethanol under 40 bar hydrogen pressure at 30° C. for 21 hours and at 50° C. for 3 hours. The residue, consisting of about 80% 3R,4R and 20% 3S,4R isomers, was triturated with tetrahydrofuran and ethanol at 50° C. for half an hour and at room temperature for 4 hours. The crystals were filtered off under suction, washed with a small amount of tetrahydrofuran/ethanol and dried to constant weight at 50° C./20 mbar, to yield 13.3 g of enantiomerically pure ethyl (3R,4R)-4-hydroxy-azepan-3-carboxylate hydrochloride in the form of white crystals.
EXAMPLE 4
As in Example 2, 0.44 g of ethyl 4-oxo-azepan-3-carboxylate hydrochloride in 9 ml of ethanol was hydrogenated with a solution of 3.2 mg of di(η 2 -acetato)(η 4 -cycloocta-1,5-diene)-ruthenium(II) and 5.8 mg (R)-MeOBIPHEP in 1 ml of diethyl ether/THF 3/1 under 40 bar hydrogen pressure at 25° C. for 23.5 hours. The yellow hydrogenation solution was evaporated on a rotary evaporator at 40°/20 mbar. With a conversion of 83%, the residue consisted, according to HPLC analysis, of 65% ethyl (3R,4R)-4-hydroxy-azepan-3-carboxylate hydrochloride with an ee>99%.
EXAMPLE 5
The hydrogenations set forth in Table 1 were carried out in an analogous manner to Examples 2-4.
TABLE 1
Asymmetric hydrogenation of ethyl 4-oxo-azepan-3-carboxylate.HX 1 )
Ex
T
Press.
Conv./
trans 3 )
cis
No
L
X
Solv.
° C.
bar
hr
%
ee
%
ee
5a
(S)-BINAP
Cl
2)
25
40
62/23
78
>99
22
73
5b
(R)-BIPHEMP
Cl
2)
25
40
90/23
66
94
34
38
5c
(R)-pTol-
Cl
2)
25
40
93/23
72
>99
28
62
BIPHEMP
5d
(R)-p-An-
Cl
2)
25
40
87/23
80
>99
20
77
MeOBIPHEP
5e
(R)-mTol-
Cl
2)
25
40
90/24
58
97
42
47
BIPHEMP
5f
(R)-pDMA-
Cl
2)
25
40
79/24
72
>99
28
95
MeOBIPHEP
5g
(R)-pPhenyl-
Cl
2)
25
40
54/23
82
>99
18
26
MeOBIPHEP
5h
(S)-3,5-Me,4-
Cl
2)
25
40
34/23
55
>99
45
61
MeO-MeOBIPHEP
5i
(R)-DiMeOBIPHEP
Cl
2)
25
40
99/23
66
>99
34
86
5j
(R)-MeOBIPHEP
Br
EtOH
40
100
99/21
76
>99
24
84
5k
″
Br
EtOH
60
100
100/21
69
>99
31
85
5l
(R)-2-Furyl-
Br
EtOH
40
100
76/29
64
98
36
95
MeOBIPHEP
5m
(R)-2-Furyl-2-
Br
EtOH
40
100
94/21
68
>99
32
69
Biphemp
5n
(R)-TriMeOBIPHEP
Br
EtOH
30
100
100/23
76
>99
24
95
5o
(R)-Cy2-
Cl
EtOH
80
20
100/22
38
>99
62
92
MeOBIPHEP
5p
(R)-MeOBIPHEP
Cl
MeOH
30
100
100/22
75
>99
25
88
5q
″
Cl
iPrOH
″
″
90/22
78
>99
22
84
5r
″
Cl
AcOH
25
40
97/23
5
>99
95
94
1) Catalyst preparation analogously to Example 2 and 3.
2) Catalyst preparation: in situ analogously to Example 4, solvent: ethanol-diethyl ether-tetrahydrofuran 9:0.65:0.35.
3) trans: compound IV or its enantiomer. Chiral diphosphine ligands with (R)-configuration give (3R,4R)-IV.
EXAMPLE 6
As in Example 3, 3.32 g of ethyl 4-oxo-azepan-3-carboxylate hydrochloride were hydrogenated in the presence of 6.3 mg of [RuCl((R)-MeOBIPHEP)(C6H6)]Cl under 40 bar hydrogen pressure at 30° C. for 19 hours and at 50° for 3 hours. The yellow hydrogenation solution was evaporated on a rotary evaporator at 40°/20 mbar. With a conversion of 95% the residue consisted, according to HPLC analysis, of 79% ethyl (3R,4R)-4-hydroxy-azepan-3-carboxylate with an ee>99%.
EXAMPLE 7
A catalyst solution was prepared in a glove box (O 2 content <1 ppm) by dissolving 1.3 ml of a 0.03 molar ethanolic HBr solution and 16.1 mg of Ru(OAc)2((R)-MeOBIPHEP) in 10 ml of ethanol and stirring for 0.5 hour. Then, 0.53 g of ethyl 4-oxo-azepan-3-carboxylate hydrobromide and 2 ml of the catalyst solution prepared above were placed in 4 ml of ethanol in an autoclave and hydrogenated at 20° C. under 100 bar hydrogen pressure for 21 hours. The yellow hydrogenation solution was evaporated on a rotary evaporator at 40°/20 mbar. With a conversion of 76%, the residue consisted, according to HPLC analysis, of 58% ethyl (3R,4R)-4-hydroxy-azepan-3-carboxylate hydrobromide with an ee>99%.
EXAMPLE 8
A catalyst solution was prepared in a glove box (O 2 content <1 ppm) by dissolving 1.0 ml of a 0.04 molar ethanolic HBF4 solution and 32.1 mg of Ru(OAc)2((R)-MeOBIPHEP) in 10 ml of ethanol and stirring for 0.5 hour. Then, 0.53 g of ethyl 4-oxo-azepan-3-carboxylate hydrobromide and 1 ml of the catalyst solution prepared above were placed in 9 ml of ethanol in an autoclave and hydrogenated at 20° C. under 100 bar hydrogen pressure for 21 hours. The yellow hydrogenation solution was evaporated on a rotary evaporator at 40°/20 mbar. With a conversion of 44% the residue consisted according to HPLC analysis of 37% ethyl (3R,4R)-4-hydroxy-azepan-3-carboxylate hydrobromide with an ee>99%.
EXAMPLE 9
67.0 g of ethyl (3R,4)-4-hydroxy-azepan-3-carboxylate hydrobromide were suspended in 500 ml of tert-butyl methyl ether and treated with 30.4 g of triethylamine. Thereafter, a solution of 54.6 g of di-tert-butyl dicarbonate in 25 ml of tert-butyl methyl ether was added at room temperature in the course of 20 minutes. Thereafter, the mixture was stirred at room temperature for a further 2 hours.
500 ml of 2N NaOH were added to the white suspension and the reaction mixture was stirred vigorously at room temperature for 2 hours. The reaction mixture was then acidified with 175 ml of 6N HCl and, after phase separation, the aqueous phase was extracted twice with 100 ml of tert-butyl methyl ether. All organic phases were washed with 150 ml of 10% sodium chloride solution, combined and dried over sodium sulphate. After removal of the solvent under reduced pressure at 40° C. the crude hydroxyacid was dissolved in 260 ml of butyl acetate at about 85° C. After seeding with pure product the suspension was cooled to −20° C. in the course of 2 hours and stirred at this temperature overnight. The suspension was filtered, washed with 100 ml of hexane and dried at 50° C. and 25 mbar, yielding 55.9 g of (3R,4R)-4-hydroxy-azepan-1,3-dicarboxylic acid 1-tert-butyl ester, melting point 121.5-122.5° C.
EXAMPLE 10
300 ml of ethyl acetate and 20.9 ml of triethylamine were added to 38.9 g of the compound prepared in Example 9. The solution was heated to reflux, then 32.4 ml of diphenylphosphoryl azide were added in the course of 30 minutes and the heating under reflux was continued for a further 2 hours. After cooling to room temperature the reaction mixture was treated with 300 ml of ethyl acetate and washed with 150 ml of 5% sodium hydrogen carbonate solution and twice with 150 ml of water. The aqueous phases were extracted twice with 300 ml of ethyl acetate. The combined organic phases were dried over sodium sulphate and evaporated at 45° C. under reduced pressure. The crude crystalline residue was dissolved in 300 ml of butyl acetate, seeded with pure product, cooled to −20° C. in the course of about 3 hours and stirred overnight. The suspension was filtered, washed with butyl acetate (pre-cooled to −20° C.) and dried at 60° C. and 25 mbar to yield 29.9 g of (3aR,8aR)-5-tert-butoxycarbonyl-2-oxo-octahydro-oxazolo[4,b-c]azepine, melting point 152.5-153.5° C.
EXAMPLE 11
25.6 g of the compound prepared in Example 10 were added to 250 ml of methanol and 250 ml of 2N NaOH. The reaction mixture was heated to reflux and held at this temperature for 3 hours. After cooling, 265 ml of solvent were distilled off at 50° C. and 150 mbar and the residue was extracted three times with 200 ml of ethyl acetate each time. The three organic phases were washed with 50 ml of 10% sodium chloride solution, combined and dried over sodium sulphate. After removal of the solvent the viscous oil obtained as the residue was dissolved in 100 ml of cyclohexane at 60° C., seeded with pure product, cooled to room temperature in the course of 2 hours and stirred overnight. The suspension was filtered, washed with 40 ml of cyclohexane and dried at 50° C. and 25 mbar, yielding 21.5 g of tert-butyl (3R,4R)-3-amino-4-hydroxy-azepan-1-carboxylate, melting point 99-100.5° C.
EXAMPLE 12
a) 4.58 g of p-toluenesulphonyl chloride dissolved in 24 ml of dichloromethane were added at room temperature in the course of 10 minutes to 4.66 g of 4-tert-butoxybenzoic acid and 6.11 g of 4-dimethylaminopyridine in 30 ml of dichloromethane. After stirring at room temperature for 2 hours, 2.30 g of the compound prepared in Example 6 in 6 ml of dichloromethane were added in the course of 10 minutes. Thereafter, the mixture was stirred at room temperature for 16 hours. The reaction mixture was washed twice with 20 ml of 1N NaOH each time and then with 40 ml of 1N HCl and 40 ml of water. All aqueous phases were extracted with 20 ml of dichloromethane. The combined organic phases were dried over sodium sulphate and the solvent was removed under reduced pressure. The residual white foam was chromatographed over 300 g of silica gel with 6.5 l of hexane-ethyl acetate (2:1). Fractions of 250 ml were collected. Fractions 8-25 were combined and the solvent was evaporated under reduced pressure, there being obtained 5.91 g of a white foam which was dissolved in 80 ml of heptane at 60° C. After stirring at −20° C. overnight the crystals were filtered off, washed with cold heptane and dried at 50° C. and 25 mbar to yield 5.34 g of tert-butyl (3R,4R)-3-(4-tert-butoxy-benzoylamino)-4-(4-tert-butoxy-benzoyloxy)-azepan-1-carboxylate, melting point 1 25.5-127.5° C.
b) 20.0 ml of 5M HCl in ethyl acetate were added at room temperature and while stirring to 5.83 g of the compound obtained in paragraph a) dissolved in 30 ml of ethyl acetate. The reaction mixture was stirred at room temperature overnight and the white precipitate was filtered off and washed three times with 5 ml of ethyl acetate each time and dried at 50° C./25 mbar for 16 hours. The white powder obtained was dissolved in 50 ml of water and stirred at 50° C. for 1 hour. The solution was then lyophilized and yielded 3.97 g of pure 3-(4-hydroxy-benzoylamino)-4-(4-hydroxy-benzoyloxy)-hexahydroazepine hydrochloride.
EXAMPLE 13
Hanseniaspora uvarum R 1052 was cultivated for 3 days at 27° C. in a Petri dish containing a solid nutrient substrate. After 3 days, 100 ml of liquid nutrient medium in a 500 ml shaking flask was seeded with a loop of this culture. This pre-culture was shaken at 27° C. for 18 hours. The cells grew to a density of 5×10 8 cells/ml (stationary phase). The entire pre-culture was used to inoculate a reactor which contained 7500 ml of nutrient medium (containing 1% yeast extract Difco: Bacto Yeast Extract # 0127-17-9, 1% Pepton Difco: Bacto Peptone # 0118-17-0 and 2% glucose in deionized water). After 18 hours, 750 ml of 50% glucose solution and immediately thereafter 29 g of the compound prepared in Example 1b dissolved in 20 ml of ethyl acetate were added in the course of 25 minutes. After 12 hours the culture solution was extracted twice with 2000 ml of ethyl acetate each time. The combined organic phases were dried over sodium sulphate. The solvent was removed under reduced pressure at 30° C. to yield 30.1 g of ethyl (3R,4S)-1-(tert-butoxycarbonyl)-4-hydroxy-azepan-3-carboxylate as a viscous orange oil.
EXAMPLE 14
a) A mixture of 28.7 g of the compound prepared in Example 13 in 200 ml of tert-butyl methyl ether and 200 ml of 2N NaOH was stirred vigorously at room temperature for 4 hours and then at 50° C. for 20 hours. After cooling, the aqueous phase was extracted twice with 100 ml of tert-butyl methyl ether each time. The organic phases were discarded. The aqueous phase was acidified cautiously with about 70 ml of 6N HCl and extracted once with 200 ml of tert-butyl methyl ether and twice with 100 ml of tert-butyl methyl ether each time. All three organic phases were washed once with 50 ml of 10% sodium chloride solution, combined and dried over sodium sulphate. After removal of the solvent under reduced pressure (40° C./25 mbar) the brown viscous oil was dissolved in 60 ml of isopropyl ether at 60° C. and left to crystallize at −20° C. for 16 hours. The crystals were filtered off, washed with a small amount of isopropyl ether, cooled to −20° C. and dried at 40° C. for 5 hours and 25 mbar, yielding 12.0 g of (3R,4S)-4-hydroxy-azepan-1,3-dicarboxylic acid 1-tert-butyl ester of melting point 98.5-101.5° C.
b) 140 ml of ethyl acetate, 9.8 ml of triethylamine and 15.9 ml of diphenylphosphoryl azide were added to 18.1 g of the compound obtained in paragraph a). The solution was heated to reflux for 2 hours, cooled, diluted with 140 ml of ethyl acetate and washed with 70 ml of 5% sodium hydrogen carbonate solution and twice with 70 ml of water each time. The three aqueous phases were separated and washed three times with 140 ml of ethyl acetate. The combined organic phases were dried over sodium sulphate and the solvent was removed at 45° C./25 mbar. The crude crystalline residue was dissolved in 140 ml of butyl acetate at about 80° C., seeded with pure product, cooled and stirred at −20° C. for 6 hours. The suspension was filtered, washed with butyl acetate (cooled to −20° C.) and dried at 60° C. and 25 mbar overnight, to yield 13.3 g of tert-butyl (3aR,8aS)-2-oxo-octahydro-oxazolo[4,b-c]azepine-5-carboxylate of melting point 158-159° C.
EXAMPLE 15
200 ml of methanol and 200 ml of 2N NaOH were added to 20.5 g of the compound prepared in Example 14b). The reaction mixture was heated to reflux and left at this temperature for 4 hours. After cooling, 200 ml of methanol were distilled off at 50° C. and 150 mbar and the residue was extracted three times with 160 ml of ethyl acetate each time. The organic phases were washed with 40 ml of 10% sodium chloride solution, combined and dried over sodium sulphate. After removal of the solvent, the viscous oil obtained as the residue was dissolved in 80 ml of methylcyclohexane at 50° C., seeded with pure product, cooled and stirred at 0° C. for 4 hours. The crystals were filtered off, washed with 20 ml of methylcyclohexane and dried at 50° C. and 25 mbar overnight, yielding 17.4 g of tert-butyl (3R,4S)-3-amino-4-hydroxy-azepan-1-carboxylate, melting point 64-67° C.
EXAMPLE 16
9.06 g of p-toluenesulphonyl chloride in 75 ml of dichloro-methane were added at room temperature to 11.5 g of 4-(tert-butoxy)-benzoic acid and 13.1 g of 4-dimethylaminopyridine in 100 ml of dichloromethane. The reaction mixture was stirred for a further 2 hours. The solution was then added in the course of 1 hour to 11.5 g of the compound prepared in Example 10 dissolved in 50 ml of dichloromethane. After stirring at room temperature for 1 hour, the reaction mixture was washed with 100 ml of 1N NaOH, 100 ml of 1N HCl and 100 ml of water. All aqueous phases were extracted with 50 ml of dichloromethane. The combined organic phases were dried over sodium sulphate and the solvent was separated under reduced pressure. The foam-like residue was dissolved in 400 ml of hot heptane and left to crystallize at room temperature overnight. The crystals were washed with 25 ml of heptane and dried at 50°/25 mbar to yield 17.3 g of tert-butyl (3R,4S)-3-(4-tert-butoxy-benzoylamino)-4-hydroxy-azepan-1-carboxylate of melting point 131.5-132.5° C.
EXAMPLE 17
262 mg of diethyl azadicarboxylate in 2 ml of tetrahydrofuran were added while stirring to 407 mg of the compound prepared in Example 16, 253 mg of 4-(tert-butoxy)-benzoic acid and 394 g of triphenylphosphine in 8 ml of tetrahydrofuran. After stirring at 50° C. for 4 hours, the solvent was removed under reduced pressure and the residue was taken up in 20 ml of cyclohexane and washed once with 20 ml of water and twice with 10 ml of 70% methanol/water each time. The aqueous-alcoholic phase was extracted twice with 10 ml of cyclohexane each time. The combined cyclohexane phases were dried over sodium sulphate and the solvent was removed under reduced pressure. The residual viscous oil was dissolved in 10 ml of hot heptane, seeded with pure end product and left to crystallize at room temperature for 18 hours and yielded 241 mg of tert-butyl (3R,4R)-3-(4-tert-butoxy-benzoylamino]-4-(4-tert-butoxy-benzoyloxy)-azepan-1-carboxylate of melting point 126-128° C. This compound can be reacted further as in Example 12b.
EXAMPLE 18
12.91 g of p-toluenesulphonyl chloride dissolved in 15 ml of dichloromethane were added at room temperature in the course of 15 minutes to 1.94 g of 4-(tert-butoxy)-benzoic acid and 2.63 g of 4-dimethylaminopyridine in 20 ml of dichloromethane. The reaction mixture was stirred for 2 hours and added in the course of 1 hour to 2.30 g of tert-butyl (3R,4R)-3-amino-4-hydroxy-azepan-1-carboxylate dissolved in 10 ml of dichloromethane. After stirring for 1 hour the reaction mixture was washed with 20 ml of 1N NaOH, 20 ml of 1N HCl and 20 ml of water. All aqueous phases were washed in succession with 10 ml of dichloromethane. The combined organic phases were dried over sodium sulphate, filtered and the solvent was evaporated. The foam-like residue obtained was dissolved in 80 ml of hot heptane and crystallized at room temperature overnight. The crystals were washed with 10 ml of heptane and dried to yield 3.23 g of tert-butyl (3R,4R)-3-(4-tert-butoxy-benzoylamino)-4-hydroxy-azepan-1-carboxylate, m.p. 134-135° C.
EXAMPLE 19
572 mg of p-toluenesulphonyl chloride in 3.5 ml of dichloromethane were added at room temperature in the course of 10 minutes to 679 mg of 4-benzoyl-benzoic acid and 764 mg of 4-dimethylaminopyridine in 5 ml of dichloromethane. After further stirring at room temperature for 2 hours 1016 mg of tert-butyl (3R,4R)-3-(4-tert-butoxy-benzoylamino)-4-hydroxy-azepan-1-carboxylate in 2.5 ml of dichloromethane were added in the course of 10 minutes while stirring. Thereafter, the reaction mixture was stirred at room temperature for a further 2.5 hours and washed with 6 ml of 1N NaOH, 6 ml of 1N HCl and 6 ml of water. All aqueous phases were extracted in succession with 6 ml of dichloromethane. The combined organic phases were dried over sodium sulphate and the solvent was evaporated. The crude product was chromatographed over 100 g of silica gel with 1.41 of hexane/ethyl acetate (2:1). Fractions of 100 ml were collected. Fractions 5-9 were combined and the solvent was evaporated. There were obtained 1.48 g of a white foam, which was crystallized from 50 ml of hot heptane, to yield 1.24 g of tert-butyl (3R,4R)-3-(4-tert-butoxy-benzoylamino)-4-(4-benzoyl-benzoyloxy)-azepan-1-carboxylate, m.p. 145-148° C., as a white powder.
EXAMPLE 20
3.0 ml of 5N HCl in ethyl acetate were added at room temperature while stirring to 922 mg of the azepine prepared in Example 19 in 4.0 ml of ethyl acetate. The reaction mixture was stirred at room temperature overnight and the precipitate was filtered off, washed three times with 2 ml of ethyl acetate and dried at 50° C./25 mbar for 16 hours yielding 0.70 g of 3-(4-hydroxy-benzoylamino)-4-(4-benzoyl-benzoyloxy)-hexahydroazepine hydrochloride. | A novel process for the manufacture of compounds of the formula
wherein R 1 and R 2 independently represent aroyl.
The present invention also concerns novel intermediates used in the novel process for making compounds of formula I. | 2 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a method of manufacturing glass in which raw material is fed as a batch to a continuous glass-melting tank furnace. The method comprises melting the batch in a melting tank and passing the melt to a refining tank via a submerged throat, heating the melt in the refining tank to de-gas it, delivering molten refined glass to a conditioning tank and there bringing it to a desired working temperature. The invention includes glass manufactured by such a method, and it extends to a continuous glass-melting tank furnace having a melting compartment comprising a tank and superstructure equipped with heating means defining a melting zone for receiving and melting raw batch material, a separate refining compartment also comprising a tank and superstructure equipped with heating means, means defining a throat allowing communication between the lower parts of the melting and refining tanks, and a conditioning tank for receiving melt from the refining tank.
In the manufacture of glass on an industial scale, various problems arise. Among these problems are that of economy regarding heating costs, and that of obtaining a properly refined, bubble-free glass.
It is of course well known that economies of scale are possible, and that a melting furnace of any given size will be most economical when run at its designed production rate. In the remainder of this specification it will be assumed that any furnace referred to is being run at a given, most economical production rate.
2. Discussion of the Prior Art
It is well known that the reactions which take place between the constituents of the raw batch during melting give rise to a considerable amount of surface foam on the melt, and bubbles of gas within the melt. It is also known that in order to refine the glass, that is to say, to ensure the substantially no bubbles remain in the melt which is drawn off for shaping, temperatures are required which are higher than those which are in fact necessary for melting the glass.
Classical glass-melting furnaces have a single tank in which melting and refining take place. Material in the tank is heated from above by burners, and the tank holds a molten mass which at the charging end of the tank is covered by unmelted or only partly melted batch material, and by foam. Somewhere close to the center of the tank there will be a point, the "hot spot" where the melt has its highest temperature and thus least density. Accordingly there will be a "spring zone" of rising currents within the melt. At the walls of the tank, the melt will be at its coolest, and there will be falling currents there. As a result, there will be a return surface current flowing from the spring zone to the charging end of the tank which tends to maintain unmelted batch and foam in the upstream portion or melting zone of the tank so that such batch and foam cannot be drawn off at the downstream end of the refining zone. Such currents will also tend to carry heat energy away to the walls of the tank where it becomes dissipated, and it is not possible to exercise any degree of independent control of the temperatures of the melt in the melting and refining zones of the tank.
In an effort to obtain greater heat economy, proposals have been made to divide the furnace into separate melting and refining tanks. By working in this way, it is possible to exercise a considerable degree of independence in control of the temperatures in the melting and refining tanks. As a result, the melting tank can be run at lower temperatures than are required in classical furnaces with consequent savings in heating costs.
An example of such a plural-tank melting furnace is described in French Patent Specification No. 2,550,523 (Saint-Gobain Vitrage SA). According to the proposals of that specification, glass feeds from the bottom of a melting tank through a throat into the base of a separate refining tank which is shaped as a chimney up which the melt flows in a uniform ascending current while being heated. The melt then passes directly to a conditioning tank where it is brought to a desired working temperature. In fact the principal source of heat both for melting and refining the glass is electric current, though optional burners over the refining chimney are shown.
The cost savings which can be realized using the previously proposed plural-tank melting furnaces are however attainable only at the expense of a lowering of the homogeneity of the glass leaving the furnace. There is also an occasional tendency for the glass to be incompletely degasified. The formation of the refining tank as a relatively deep chimney and the employment of submerged electrical heaters to maintain a strong ascending current of glass in this chimney as proposed in the above mentiioned French Patent Specification No. 2,550,523 would not avoid these disadvantages.
SUMMARY OF THE INVENTION
It is an object of this invention to provide a method of manufacturing glass which facilitates the economical production of glass of a given composition and quality.
According to the present invention, there is provided a method of manufacturing glass in which raw material is fed as a batch to a continuous glass-melting tank furnace, which method comprises melting the batch in a melting tank and passing the melt to a refining tank via a submerged throat, heating the melt in the refining tank to de-gas it, delivering molten refined glass to a conditioning tank and there bringing it to a desired working temperature, characterized in that the refining tank is divided into upstream and downstream refining cells by a transverse sill, and the melt in the upstream refining cell is heated to create a spring zone located towards the downstream end of that cell and a circulation of melt in that cell which feeds the spring zone.
The adoption of the present invention facilitates the economical production of glass of a given composition and quality.
By virtue of the presence of the spring zone in the upstream refining cell, there will he a better defined circulation of the melt within that cell. This promotes refining of the melt, and also, it promotes a good mixing of the melt in that region. Furthermore, it is likely that surface return currens will be created to flow in the upstream direction over part of the area of the melt in the upstream refining cell. Any such currents would act to constrain foam floating on the melt there from flowing in the downstream direction, over the transverse sill and towards the conditioning tank. Melt flowing in the downstream direction over the transverse sill will be close to the spring zone and thus close to the hottest part of the tank, and because of the relative shallowness of the melt over the sill, any residual bubbles in the melt can escape fairly easily there. Thus, for a given composition and quality of glass being produced, the method can be performed with the refining tank being run at a lower temperature than would otherwise be required, and thus more economically.
Furthermore, because of the pattern of current in the melt in the upstream portion of the refining tank, a greater bubble population can be tolerated in the melt feeding into the refining tank. Accordingly, the melting tank can also be run cololer for a given composition and quality of glass, thus affording further economies.
A further advantage of manufacturing glass by a method according to the present invention is that it facilitates switching over from the production of glass of one composition to glass of another. Because the furnace is divided up into separate melting and refining tanks, and because the refining tank sole is provided with a sill, distinct current circulation patterns are set up in the melt. The result is that when the batch composition is changed, for example from a batch for producing clear glass to one for producing colored glass, the change in composition in the melt tends to take place much more rapidly than it would otherwise, and the quantity of waste glass of an intermediate composition is reduced. It may be noted here that such waste glass of an intermediate composition is often difficult to make use of even as cullet for remelting. If such waste glass is to be used as cullet, the necessary care must be taken to adjust the other ingredients of the raw batch constantly depending on the varying composition of the cullet.
The shape of the volume occupied by the melt in the upstream refining cell has an important influence on the currents in that cell. In preferred embodiments, the level of the surface of the melt is so regulated that the length of the upstream refining cell is greater than the mean depth of melt in that cell. The adoption of this feature is conducive to the formation of a continuous pattern of circulating currents in the upstream part of that cell, and this further promotes refining and homogenization of the melt in that region.
Advantageously, the mean length of the upstream refining cell is at least equal to half of its mean width, and preferably, the transverse sill is spaced from the upstream end wall of the refining tank by a distance which is at least equal to the mean width of the upstream refining cell. When adopting one or both of these features, the angle subtended by the upstream end wall of the refining tank at the spring zone is less than it otherwise would be. As a result, any surface return currents flowing from the spring zone towards the upstream end wall of the refining tank make a more acute angle with the longitudinal direction of the furnace and they may thus have an improved restraining effect on any foam on the melt in the refining tank and tend to pin it against the upstream end wall of the refining tank so that it cannot flow to the conditioning tank.
It is preferred that the level of the surface of the melt is so regulated that the mean depth of melt above the transverse sill is at most two fifths of the mean depth of the melt in the downstream refining cell. In operation, there is likely to be a return current of molten glass which flows back from the downstream refining cell, over the transverse sill, and into the upstream refining cell. This return current, which may even flow from the conditioning tank, will consist of glass which cooler than that which forms a forward current flowing downstream from the upstream refining cell. As a result, the forward current flowing over the transverse sill will tend to be confined to a surface layer which, by the adoption of this preferred feature, will be rather less than two fifths of the depth of the melt in the downstream refining cell. Since the melt feeding that forward current must come fom the rather close spring zone at the hottest part of the refining tank, that forward current will itself be strongly heated, and strong heating of a rather thin surface layer is highly beneficial for refining of the melt.
The furnace may be heated electrically using electrodes immersed in the melt, and/or by burners, the choice being a matter of convenience and economy. In preferred embodiments of the invention, the refining tank is heated at least in part by heaters which heat the melt most strongly at a location towards the downstream end of the upstream refining cell. This is a very simple way of creating a spring zone in the melt close to the transverse sill, without unduly heating the wall structure which separates the melting and refining compartments, with consequent benefits to the resistance of that wall structure to erosion by the melt. The adoption of this feature also promotes heating of the melt flowing over the transverse sill.
It is also preferred that there is a heater located to heat the melt above said transverse sill. This promotes substantially complete refining of the melt.
Advantageously, the depth of the melt in at least a part of the melting tank is less than the depth of the melt in at least a part of the refining tank. By adopting this feature, the melting tank can be made shallower so that it will contain less melt, and as a result heating economies can be effected. It will be appreciated that most if not all of the melt in the melting tank will be covered by unmelted batch material or by foam. This tends to shield the sole of the melting tank from the heating effect of any burners in the melting compartment. The refining tank on the other hand should contain no unmelted material, and any foam there should be substantially confined to its upstream end. A certain depth of melt in the refining tank is therefore desirable, not only for allowing room for a beneficial circulation of the melt, but also for allowing a certain measure of shielding of the refining tank sole by the melt against the effect of burners over that tank, so as to reduce the tendency of the refining tank sole to be eroded by the melt.
Preferably, the melt flows from the melting tank into the refining tank via a rising passageway. This is effective in preventing return currents flowing upstream from the refining tank back into the melting tank, and is therefore beneficial for heat economy, and also for promoting a more rapid changeover between the manufacture of glasses of different compositions.
In some such embodiments, the melt is advantageously caused to flow from the melting tank into the refining tank through a throat located beneath the level of the sole of the upstream refining cell. Dropping the level of the throat in this way tends to give an increased cooling at the throat: the sole and end walls of the throat may project from the base of the tank furnace so that there will be increased heat radiation from the refractory parts making up the throat. As a result, the melt entering the refining tank will tend to be cooler, and it will therefore enter the refining tank as a forward flowing bottom current which is more viscous than the melt already in the refining tank. It will be apparent that the flow rates and the forces driving the forward and return currents in the refining tank upstream of the transverse sill must be in balance. Accordingly, because of the viscosity differences between the currents in the melt there, the cooler bottom current will take up more space and will constrict the return current to a relatively shallow surface layer. The surface return current will therefore be caused to flow faster. This is beneficial for stabilizing the current circulation and it promotes the confinement of any foam against the wall structure separating the melting and refining compartments, and effective refining of the melt.
Alternatively, or in addition the melt may with advantage be caused to flow over a second sill provided towards the upstream end of the upstream refining cell. Such a second sill can act as a barrier which restricts the volume of the space occupied by the surface return current, and accordingly also has the effect of increasing its speed. Again, current stabilisation, foam retention and effective refining are promoted. Care must be taken when adopting this feature however, because it has the consequence that the forward current flowing along the sole of the refining tank will be at an increased temperature. This increase in temperature should not be so high as to cause unacceptable erosion of the sole of the upstream refining cell.
Advantageously, the melt in the upstream refining cell is heated by at least one immersed electrode. The use of such an electrode will have an effect on the density of the melt in its immediate vicinity, and it accordingly enables very fine control of the pattern of flow currents in the melt. In particular, by locating such an electrode at or slightly upstream of the spring zone, the location of the spring zone can be better defined or stabilized, thereby promoting a beneficial circulation of the melt for refining and mixing it.
In some preferred embodiments of the invention, gas is injected into the melt at the spring zone in the upstream refining cell. It may seem somewhat contradictory to introduce gas into the melt in the refining tank, but it should be kept in mind that the purpose of refining is to remove the rather small gas bubbles in the melt due to melting reactions. Much larger gas bubbles can be introduced by injection. It will be appreciated that the forces causing bubbles in the melt to rise depend on the cube of the bubble radius while the forces hindering such rise depend on the square of their radius. Such injected bubbles will have the effect of stabilizing the position of the spring zone, constraining the rising currents there to flow in a more nearly vertical direction and more quickly, and this promotes a stable pattern of circulating currents in the melt and thus refining of the melt. Such gas injection is also beneficial in reducing the time required for changing the composition of the glass being produced.
In embodiments of the invention in which the melt is heated by one or more immersed electrodes and in which gas is injected as discussed above, it is especially preferred that the melt in the upstream refining cell is heated by atleast one immersed electrode at a location closer to the upstream end of that cell than a location where gas is injected into the melt. The adoption of this preferred feature has been found to promote a particularly favorable and stable pattern of flow currents within the melt in the upstream refining cell.
Advantageously, the melt is caused to flow from the refining tank to the conditioning tank via a neck. This provides a constraint on flow between the refining tank and the conditioning tank, in particular in reducing return currents from the conditioning tank to the refining tank, which is beneficial for the pattern of current flow in the furnace. Also such constraint is of advantage if it is desired to change from the production of glass of one composition to glass of another composition: such changeover can be effected more quickly with a consequent saving in waste glass of an intermediate composition.
Preferably, the melt is caused to flow from the refining tank to the conditioning tank beneath a floater provided at the downstream end of the refining tank. The presence of such a floater causes the melt entering the conditioning zone to do so from subsurface currents in the refining tank, and it provides an effective final safety barrier against the entry of surface foam into that conditioning zone.
In the most preferred embodiments of the invention, the maximum temperature of the glass in the refining tank is kept higher than the maximum temperature of the glass in the melting tank. This promotes fuel economy insofar as the melting tank is not heated to the high temperatures required for refining the glass.
Advantageously, the maximum temperature of the glass in the refining tank is maintained at a value which is at least 70° C. greater than the maximum temperature of the glass in the melting tank. This promotes rapid refining of the glass. In fact, the speed of refining is increased by increasing the temperature in the refining tank, so for the most rapid refining, the tank could be run at a temperature as hot as could be withstood by the refractory material of which it is formed. However in order to limit heat losses from the refining tank, such temperature differential is preferably not more than 300° C. It has been found that, when using any given furnace and for any given quality and composition of glass, the maintenance of such a temperature differential gives the greatest benefit in fuel economy.
The invention is applicable to the manufacture of many different types of glass. It will be appreciated that the optimum temperatures to be maintained in the melting and refining tanks will depend on the type of glass being produced. For example borosilicate glasses will in general require higher temperatures than soda-lime glasses to achieve a given quality. However general statements for all types of glass can be made by referring to the temperatures at which the logarithm (to base 10) of the viscosity of the glass in Poises (10 P equal 1 pascal second) has a given value, say N: this is denoted by the expression "the N temperature". In this description references to the N temperature will be followed by references in parenthesis to actual temperature values which are the corresponding temperatures for soda-lime glass.
It is preferred that the maximum temperature in the refining tank is maintained between the 2.08 temperature (1450° C.) and the 1.85 temperature (1525° C.). Alternatively, or in addition, it is preferred that the maximum temperature in the melting tank is maintained between the 2.42 temperature (1350° C.) and the 2.16 temperature (1425° C.) Within those ranges, the maximum temperature required in the refining tank is largely governed by the desired quality of the glass being produced, and the maximum temperature required in the melting tank is governed both by glass quality and by the presence or absence of melting accelerators such as sodium sulphate which may be included in the batch. Thus for example when melting glass for the production of float glass, it would be desirable to work towards the upper ends of the specified temperature ranges, but for the manufacture of for example bottle glass it would be sufficient to work at the lower ends of those temperature ranges, especially if melting accelerators were to be included in the batch material.
By way of comparison, it amy be noted that the maximum temperature in a conventional furnace in which glass for the production of float glass is melted and refined in a single tank is, for a particular batch composition, between the 1.85 temperature (1525° C.) and the 1.75 temperature (1550° C.). The present invention can be used for the production of float glass of the same quality from the same batch composition while working within the temperatures ranges referred to above. Accordingly, the maximum temperature in the refining zone can be lower, and that in the melting zone can also be lower, than when using a conventional process, and this reduced requirement for high temperatures leads to further economy in the use of fuel.
In preferred embodiments of the invention, substantially the whole surface of the melt in the melting tank is covered by unmelted and partially melted batch material. This ensures concentration of heat onto the batch material to be melted, and substantially avoids the presence of clear surface areas of the melt in the melting tank. If such areas were present, there would be a direct path for radiation from the tank superstructure to the refractory material forming the sole of the tank and this could cause overheating of that material. Such overheating would lead to increased heat loss through the melting tank sole, and would also shorten the useful working life of the refractory sole material.
Advantageously, the plan area of the refining tank is at least as great as that of the melting tank. The adoption of this feature has been found to be particularly beneficial for the economical manufacture of well refined glass.
In some preferred embodiments of the invention, melt is fed from the conditioning tank to a float chamber. The use of a float chamber is particularly advantageous for the manufacture of sheet glass of high quality. Alternatively or in addition, melt can be fed from the conditioning tank to a drawing machine. This is particularly appropriate for the manufacture of sheet glass which is too thin to be made conveniently by the float process.
The present invention includes glass manufactured by a method as hereinbefore defined.
The invention also extends to the furnace for the manufacture of glass. The invention provides a continuous glass-melting tank furnace having a melting compartment comprising a tank and superstructure equipped with heating means for receiving and melting raw batch material, a separate refining compartment also comprising a tank and superstructure equipped with heating means, means defining a throat allowing communication between the lower parts of the melting and refining tanks, and a conditioning tank for receiving melt from the refining tank, characterised in that the refining tank is divided into upstream and downstream refining cells by a transverse sill, and the heating means in the refining compartment is arranged to heat melt in the upstream refining cell to create a spring zone located towards the downstream end of that cell and a circulation of melt in that cell which feeds the spring zone.
Such a furnace facilitates the economical production of glass of a given composition and quality, for example by a process as hereinbefore defined. The furnace construction allows controlled circulation of melt contained in the upstream cell of the refining tank which is beneficial for refining the glass. Also, such a furnace is quite easy to build. For example in contrast to the furnace disclosed in French Patent Specification No. 2,550,523 (Saint-Gobain Vitrage, SA), substantially the whole furnace comprising the melting tank, the refining tank and the conditioning zone can be constructed with its sole at the same or nearly the same level. Because the furnace of French Patent Specification No. 2,550,523 requires a vertical refining chimney, it is necessary that the soles of the melting and conditioning zones be at very different levels, and this in turn involves substantial additional work in building the support structure for the conditioning zone (and any forming apparatus downstream of the conditioning zone) which is not required for the construction of a tank furnace according to the present invention.
Preferably, the mean depth of the upstream cell of the refining tank is less than the length of that cell. This promotes the formation of a continuous pattern of ciculating currents in a melt in the upstream part of that cell, and this further promotes refining and homogenization of the melt in that region.
Advantageously, the mean length of the upstream cell of the refining tank is at least equal to half of its mean width, and it is preferred that the transverse sill is spaced from the upstream end wall of the refining tank by a distance which is at least equal to the mean width of the upstream refining cell. The adoption of one or both of these features has a beneficial effect on the pattern of current flow in the melt in that region of the refining tank, and it also allows room for adequate heating of that melt without subjecting the wall structure separating the melting and refining compartments to such excessive heat as would unnecessarily shorten it working life due to erosion.
Preferably, the mean height of the transverse sill above the sole of the downstream cell of the refining tank is at least three fifths of the means depth of that downstream cell. A sill of such height is beneficial for stabilising current flow patterns and for promoting good refining of melt flowing over it.
Advantageously, the refining compartment is provided with heaters which, considered as a group, are located closer to said transverse sill than to the upstream end of that compartment. This is a very simple way of providing the heating means required. Of course such heaters may be supplemented with other heating means if required, for example with heating electrodes which project into the refining tank.
Preferably, there is a heater located to heat material flowing above the transverse sill. This is beneficial for ensuring heating and refining of a forward flowing surface current of the melt which flows across that sill.
Advantageously, the sole of at least a part of the melting tank is at a higher level than the sole of at least a part of the refining tank. This allows the use of a melting compartment of smaller capacity which can give useful savings in fuel consumption, while at the same time allowing a measure of protection to the sole of the upstream cell of the refining tank against overheating and erosion, due to the depth of melt which is above it in use.
Preferably, the throat communicates with the upstream refining cell via a rising passageway. This is effective in preventing return currents flowing upstream from the refining cell back into the melting tank, and is therefore beneficial for heat economy, and also for promoting a more rapid changeover from the manufacture of glass of one composition to glass of another.
In some such embodiments, it is preferred that the throat is beneath the level of the sole of the refining tank. It is quite simple to drop the level of the sole of the furnace over the rather small area necessary to define such a throat. In addition to having a beneficial effect on the flow pattern of the melt between the shadow wall and the transverse sill as has previously been adverted to, dropping the level of the throat in this way allows the refractory defining the throat to be maintained at a lower temperature, thus making that refractory less liable to erosion.
Alternatively, or in addition, a second sill may be provided towards the upstream end of the refining tank. Such a second sill is very easy to install, and can have a simiar beneficial effect on the flow pattern of the melt. This sill can also act to shade the region of the throat from the heaters in the refining zone, thus again prolonging the working life of the refractory defining the throat. It will be appreciated that that second sill will itself be exposed to quite strong heating in operation of the furnace, so it should be made of a rather high grade refractory material. Also, the use of such a sill can have the effect of increasing the temperature of the currents flowing along the bottom of the upstream refining cell between the two sills, and consideration should accordingly be given as to whether it is necessary to make that portion of the sole of a higher grade refractory than would otherwise be done.
Advantageously, at least one heating electrode is provided for immersion in the melt in the upstream refining cell. The use of such an electrode enables very fine control of the pattern of flow currents in the melt. In particular, by locating such an electrode at or slightly upstream of the spring zone, the location of the spring zone can be better defined or stabilized, thereby, so promoting a beneficial circulation of the melt for refining and mixing it.
In some preferred embodiments of the invention, a means is provided for injecting gas into the refining tank at the spring zone. This stabilizes the spring zone and has a beneficial effect on the current circulation pattern in the melt.
In embodiments of the invention in which the melt is heated by one or more immersed electrodes and in which gas is injected as discussed above, it is especially preferred that at least one heating electrode is provided at a location closer to the upstream end of that cell than the location of the gas injection means. The adoption of this preferred feature has been found to promote a particularly favorable and stable pattern of flow currents within the melt in the upstream refining cell.
The refining tank is preferably connected to the conditioning tank via a neck. Such a neck is very simple to construct, and its use has a favorable effect on the flow pattern in the melt, particularly in reducing return currents, and on the speed with which a change can be made from the production of glass of one composition to glass of another.
Advantageously, a floater is provided at the downstream end of the refining tank. Such a floater can prevent any material floating on top of the melt from flowing further downstream. If such a floater is provided located in a neck between the refining tank and the conditioning tank, it can be made shorter than if it is located in the refining tank itself.
Advantageously, the plan area of the refining tank is at least as great as that of the melting tank. The adoption of this feature has been found to be particularly beneficial for the economical manufacture of well refined glass.
The invention is particularly suitable for the production of a high quality melt which is suitable for forming into sheets, for example by the float process. In preferred embodiments, therefore, the conditioning tank is connected for feeding molten glass to a float chamber.
Alternatively, or in addition, it is preferred that the conditioning tank is connected for feeding molten glass to a drawing machine. Such embodiments are particularly suitable for the production of sheet glass which is thinner than can conveniently be made by the float process.
BRIEF DESCRIPTION OF THE DRAWINGS
The present invention will no be further described with reference to the accompanying diagrammatic drawings in which:
FIGS. 1 and 2 are respectively sectional plan and side views of a continuous glass-melting tank furnace according to the invention, which comprises a melting compartment, a refining compartment and a conditioning tank.
FIG. 3 is an enlarged cross sectional side view of the refining compartment of the tank furnace of FIG. 1, and
FIG. 4 is a cross sectional side view of the refining compartment of a first alternative embodiment of tank furnace.
FIGS. 5 and 6 are respectively cross sectional plan and side views of a second alternative embodiment of tank furnace,
FIG. 7 is a cross sectional side view of a third alternative embodiment of tank furnace,
FIGS. 8 and 9 are respectively cross sectional plan and side views of a fourth alternative embodiment of tank furnace,
FIGS. 10 and 11 are respectively cross sectional plan and side views of a fifth alternative embodiment of tank furnace,
FIGS. 12 and 13 are respectively cross sectional plan and side views of a sixth alternative embodiment of tank furnace, and
FIG. 14 is a cross sectional side view a seventh alternative embodiment of tank furnace,
DESCRIPTION OF THE PREFERRED EMBODIMENTS
In FIGS. 1 and 2, a continuous glass-melting tank furnace comprises a melting compartment 1 including a tank 2 which is in melt flow communication with a tank 3 of a refining compartment 4 via a submerged throat 5 beneath a wall structure 6 which constitutes the downstream end wall of the melting tank 2 and the upstream end wall of the refining tank 3. On the sole of the refining tank 3 is located a transverse sill 7 which divides the refining tank 3 into upstream and downstream refining cells 8 and 9. In the embodiment illustrated, the length of the upstream refining cell 8 is greater than its depth, and that length is also greater than the width of the upstream refining cell 8. At the downstream end of the refining tank 3 is provided a neck 10 giving communication with a conditioning tank 11 whence molten glass may be drawn off and fed to a glass shaping apparatus not shown. Such a glass shaping apparatus may, and preferably does, comprise a float chamber and/or a flat glass drawing machine. The outlet of the conditioning tank 11 illustrated is in fact designed for feeding to a float chamber. The shaping apparatus may alternatively, or in addition, take the form of one or more rolling machines for the production of figured glass, or molding machines for the production of glass bottles or other hollow ware. It will however be appreciated that quality requirements for figured glass and hollow ware are not usually so high as those for sheet glass.
A second optional sill 12 is provided a short distance downstream of the throat 5 to define a rising passageway 13 through which the melt enters the refining tank 3. For this purpose, the top of that second sill 12 is located at a level which is higher than the top of the throat 5.
The melt surface level is represented in FIG. 2 by the line 14. A floater 15 is positioned at the downstream end of the refining compartment 4 in the entrance of the neck 10.
In FIGS. 3 and 4, those parts which are also shown in FIG. 1 or 2 are allotted the same reference numerals. FIGS. 3 and 4 also show how the wall structure 6 separates the atmospheres contained by superstructures 16 and 17 respectively of the melting and refining compartments 1 and 4. Also shown is the downstream end burner 18 for each melting compartment 1, and three transverse burners 19, 20, 21 in each refining compartment 4, of which the downstream one 21 is located over the transverse sill 7. These burners 19, 20, 21 are located and adjusted to maintain a spring zone represented by arrow 22 in the upstream cell 8 of the refining tank 3 which is upstream of the transverse sill 7, but closer to that sill than to the wall structure 6.
In the embodiment shown in FIGS. 1, 2 and 3, the sole 23 of the melting tank 1 is at the same level as the sole 24 of the upstream cell 8 of the refining tank 3, upstream of the transverse sill 7, and this level is slightly higher, for example about 0.3 m, than the level of the sole 25 of the refining tank 3 downstream of that transverse sill 7 which continues to form the sole of the neck 10 and the conditioning zone 11.
In operation of the embodiment shown in FIG. 3, there will be a forward flow of melt through the throat 5 and up the rising passage 13. Because of the configuration of this rising passage, there can be substantially no return flow from the refining tank 3 to the melting tank 2, provided that the refining tank is maintained hotter than the melting tank so that the melt in the refining tank is less dense than that entering it. Melt flowing up the rising passage 13 will flow over the second sill 12 as a sub-surface current because it is cooler than the melt which has previously been exposed to the burners 19 to 21, and it will therefore also form a falling current on the downstream side of that second sill 12 feeding a forward flow of melt in the upstream refining cell 8 between the two sills, leading towards the spring zone 22. Because the melt there is at its hottest and least dense, it will form a rising current which will flow outwards in all directions across the surface of the melt. Part of that surface flow will be constituted by return surface currents flowing back towards the wall structure 6. The angle subtended by the wall structure 6 at the spring zone 22 will clearly be smaller as the spacing between them increase. As a result, the surface return currents directed back towards the wall structure in the embodiment illustrated can have a sufficient component in the longitudinal direction of the furnace to confine against the wall structure any bubbles which rise to the surface of the melt in the upstream refining cell 8 upstream of the spring zone. Surface return currents flowing to the wall structure will be cooled slightly by contact with that wall structure and/or by contact with melt entering the upstream refining cell from the melting tank, and they will therefore descend to join freshly introduced melt and circulate back down the second sill 12 and along the sole 24 to the spring zone 22. Surface currents flowing downstream from the spring zone 22 will flow over the transverse sill 7 into the downstream cell 9 of the refining compartment 4 and thence through the neck 10 to the conditioning tank 11. In the conditioning tank 11, (not shown in FIG. 3), melt coming into contact with the side and end walls will also be cooled to form sinking currents, and these will feed bottom return currents flowing aong the sole 25. Flow of these currents back into the refining tank 3 will be restricted by the presence of the neck 10, but nevertheless, there will be some melt in these currents which will flow to form a rising current at the downstream side of the transverse sill 7 and this will flow up over that sill and descend to feed the base of the spring zone 22 from the downstream end. The presence of this over sill return current forces a very shallow forward surface current over the sill so that melt in that forward current is well exposed to heat from the downstream burner 21 over the sill 7. This system of currents promotes good mixing and refining of the melt in the refining tank.
In the absence of the optional second sill 12, melt flowing through the throat 5 will tend to flow as a forward bottom curent directly to the base of the spring zone 22. Again return surface currents will be generated and maintained, but since these return currents will not be impeded by the presence of the second sill, they can descend to the base of the wall structure and then join the forward bottom current feeding the base of the spring zone. In this case, there might be a slight return current through the throat.
With the presence of the second sill 12, the sole 24 of the upstream refining cell 8 will tend to be hotter than when that sill is not present. This will of course lead to an increased rate of erosion of the sole 24, even to such an extent as to shorten its working life to an unacceptable degree. It may not always be possible to compensate for this adequately by reducing the heating of the upstream refining cell 8 having regard to the temperatures which are necessary to effect adequate degassing of the melt. One way of compensating would be to make the sole 24 of a higher grade refractory than would be required if the second sill were not present. Another way of compensating would be to drop the level of the sole 24 of the upstream refining cell 8, for example to the level of the sole 25 of the downstream refining cell 9. The additional depth of melt in the upstream refining cell 8 would than have an increased shielding effect on the sole 24 against radiant heat from the burners 19 to 21.
In the embodiment of FIG. 4, the sole 23 of the melting tank 2 slopes down at its downstream end as shown at 26 to form a sunken throat 5, below the level of the sole 24 of the upstream refining cell 8. That throat sole 27 is connected to the upstream refining cell sole 24 by a wall 28 which, with the wall structure 6 defines a rising passage 13 for the melt to enter the refining tank from the melting tank. A sill 29 is provided in the melting tank 2 at the junction between the horizontal and sloping portions 23 and 26 of the tank sole to encourage a rising flow of melt in the melting tank 2 and thus impede any direct forward bottom flow of partially melted material from the melting tank into the throat. In this embodiment, the flow pattern downstream of the immediate vicinity of the throat is very similar to that of the FIG. 3 embodiment without the optional second sill. It will be noted though that there will be very little, if any, possibility of glass forming a return current flowing back through the throat from the refining tank. It is to be noted that such a second sill could be provided in the embodiment shown in FIG. 4 if desired, for example above the throat end wall 28.
In the FIG. 4 embodiment, the soles 24, 25 of the upstream and downstream refining cells 8, 9 are at the same level, a level which is lower, for example 30 cm lower, than the level of the horizontal sole portion 23 of the melting tank.
A specific embodiment of continuous glass-melting tank furnace designed in accordance with FIGS. 1 to 3 for the production of glass at a rate of 50 tonnes per day has the following dimensions.
______________________________________Width of melting tank 2 4.0 mWidth of throat 5 0.7 mWidth of refining tank 3 4.0 mWidth of neck 10 1.2 mWidth of conditioning tank 11 3.6 mDepth of melting tank 2 0.9 mHeight of throat 5 0.3 mDepth of upstream refining cell 8 0.9 mDepth of downstream refining cell 9 1.2 mDepth of neck 10 1.2 mDepth of conditioning tank 11 1.2 mDepth of melt above transverse sill 7 0.3 mDepth of melt above second sill 12 0.3 mLength of melting tank 2 4.5 mLength of throat 5 1.2 mLength occupied by passageway 13 0.6 mLength occupied by tranverse sill 7 0.6 mLength between sills of upstream cell 8 3.5 mLength occupied by second sill 12 0.6 mLength of downstream refining cell 9 4.0 mLength of neck 10 3.0 mLength of conditioning tank 11 6.0 m______________________________________
For the production of highly refined soda-lime glass of ordinary composition, such a furnace may be run with a maximum melt temperature in the melting tank of about 1375° C. (the 2.33 temperature) while the maximum temperature of the melt in the refining tank is about 1475° C. (the 2.0 temperature).
In the embodiment shown in FIGS. 5 and 6, the melting compartment 1 is of the end-fired or horseshoe-flame type in which burner ports such as 30 are provided in the charging end wall 31. A plurality of electrodes 32 are immersed in the melt in the melting tank 2 to provide supplementary heat energy for melting the batch. The sole 23 of the melting tank 2 and the sole 24 of the upstream refining cell 8 are on the same level so the melt enters that refining cell through a straight throat 5. The sole 25 of the downstream refining cell 9, the neck 10 and the conditioning tank 11 are also at that same level.
The refining compartment 4 is cross-fired by using three burner ports 19, 20, 21 at each side. The downstream burner port 21 shown is located above transverse sill 7 separating the upstream and downstream refining cells 8 and 9. Additional heat energy is supplied to the upstream refining cell 8 using booster electrodes 33 projecting upwardly through the sole 24 of that cell, of which one electrode is located substantially in the center of the cell 8 and two are located towards the upstream end wall structure 6 of the refining compartment. The use of such booster electrodes 33 in the upstream refining cell 8 is beneficial for promoting a desirable and stable flow pattern of convection currents in the melt in that cell.
The length of the upstream refining cell 8, that is the distance between the transverse sill 7 and the upstream end wall 6, is greater than its width, and its width is in turn greater than the depth of melt in that cell. The melting tank 2 and the refining tank 3 have the same width. The depth of melt above the transverse sill 7 is about one quarter of the total depth of melt in the tank furnace.
Refined melt leaving the downstream refining cell 9 passes beneath floater 15 to enter the neck 10 and thence flows into the conditioning tank 11 to the outlet end of the furnace, here shown as a pouring spout 34 for supplying molten glass to a rolling machine or float chamber (not shown).
A specific embodiment of continuous glass-melting tank furnace designed in accordance with FIGS. 5 and 6 for the production of glass at a rate of 250 tonnes per day has a melting tank 2 which is 89 m 2 (8.5 m×10.5 m) in plan area, a refining tank 3 which is 148 m 2 (8.5 m×17.4 m) in plan area, and a conditioning tank 11 which is 120 m 2 in plan area.
In the furnace of FIG. 7, the melting compartment 1 is cross-fired, and electrodes 32 project up through the sole 23 to provide supplementary energy for melting the batch. The level of the melting tank sole 23 is dropped at its downstream end so that the throat 5 is beneath the level of the melting tank sole. The sole 24 of the upstream refining cell 8 is at the level of the sole of the throat as is the sole 25 of the downstream refining cell and the sole of the neck 10 and conditioning tank 11.
The refining compartment 4 of the furnace of FIG. 7 is a broadly similar design to that shown in FIGS. 5 and 6, except for the arrangement of booster electrodes 33 in the upstream refining cell. In FIG. 7, there is a row of four vertical electrodes 33 located closer to the sill 7 than to the upstream end wall 6. The electrodes 33 may for example be located substantially along the neutral line of the cell 8, that is, the transverse line passing through the spring zone (as compared to 22 in FIGS. 3 and 4). The use of such electrodes promotes upward flow of melt at the spring zone and gives a better definition of, or redefines, the location of that spring zone, thus promoting good mixing and refining of the melt.
On leaving the refining tank 3, the melt enters the neck 10 passing beneath a bridgewall 35 which is clear of the surface of the melt, and then passes to the conditioning tank 11 whence it may be fed to any desired glass shaping apparatus.
The length of the upstream refining cell 8, that is the distance between the transverse sill 7 and the upstream end wall 6, is greater than its width, and its width is in turn greater than the depth of melt in that cell. The melting tank 2 and the refining tank 3 have the same width. The depth of melt above the transverse sill 7 is about two-fifths of the total depth of melt in the upstream refining cell 8.
A specific embodiment of continuous glass-melting tank furnace designed in accordance with FIG. 7 for the production of glass at a rate of 500 tonnes per day has a melting tank 2 which is 141 m 2 (10 m×14.1 m) in plan area, a refining tank 3 which is 234 m 2 (10 m×23.4 m) in plan area, and a conditioning tank 11 which is 160 m 2 in plan area.
In the embodiment of FIGS. 8 and 9, the design of melting compartment 1 is substantially as described with reference to FIGS. 1 and 2. The sole of the entire furnace is at the same level and the melt enters the refining compartment 4 through a straight throat 5.
The refining compartment 4 is of broadly similar design to that described with reference to FIGS. 5 and 6, the main differences being the arrangement of booster electrodes 33 and the provision of gas injectors 36 in the upstream refining cell 8. Along the neutral line of that cell, a row of three gas injectors 36 projects upwardly through the sole 24. The central injector 36 is located to define the spring zone. Vertically spaced pairs 33a, 33b of booster electrodes project into the melt in refining cell 8 through its side walls. At each side of the refining cell, one pair 33a of booster electrodes is located spaced slightly upstream of the neutral line, and the other pair 33b is located spaced slightly downstream of that line. This arrangement of gas injectors and booster electrodes is highly beneficial for obtaining a well-defined spring zone and a stable flow pattern in the melt for good mixing and refining.
In a variant, the downstream pairs of booster electrodes 33b are omitted, and in another variant, additional upstream pairs of booster electrodes 33 are provided close to the indicated positions 33a. These arrangements are also highly beneficial for achieving good refining and mixing of the melt.
On leaving the refining tank 3, the melt enters a neck 10 which is narrower than the necks 10 of previously described embodiments. Accordingly, no floater 15 or bridgewall 35 is provided at the entrance to the neck 10 in this embodiment. From the neck 10, the melt passes into a conditioning tank 11 having twin outlets for feeding two glass shaping machines, for example drawing machines.
A specific embodiment of continuous glass-melting tank furnace designed in accordance with FIGS. 8 and 9 for the production of glass at a rate of 100 tonnes per day has a melting tank 2 which is 36 m 2 (6 m×6 m) in plan area, and a refining tank 3 which is 59 m 2 (6 m×9.8 m) in plan area.
FIGS. 10 and 11 illustrate an embodiment of a continuous glass-melting tank furnace which is particularly suitable for the manufacture of glass at rather high production rates, for example 600 tonnes per day. The entire furnace sole is at one level. The melting compartment 1 is of similar design to that described with reference to FIGS. 1 and 2, and the melt passes from the melting tank 2 into the refining tank 3 via a straight throat 5 which is wider than the throats 5 of previously described embodiments. The refining tank 3 is wider than the melting tank 2.
The refining compartment 4 is cross-fitted, and because of its high design capacity it is provided with four burner ports at each side. The downstream burner port 21 is located to heat melt downstream of the transverse sill 7 as well as melt flowing over that sill. The sill 7 occupies some two-thirds of the total depth of the melt, and it is located at a distance from the upstream end wall 6 of the refining tank which is about twice the depth of the melt, and approximately five-sixths of the width of the refining tank.
A row of four gas injectors 36 is arranged along the neutral line of the upstream refining cell 8. A staggered transverse row of three booster electrodes 33 projects upwardly through the sole of that cell at a location which is close to but upstream of the neutral line. A second row of booster electrodes 33c is preferably provided upstream of the first. If desired, such a second row of booster electrodes could be located downstream of the neutral line.
A specific embodiment of a continuous glass-melting tank furnace designed in accordance with FIGS. 10 and 11 for the production of glass at a rate of 600 tonnes per day has a melting tank 2 which is 150 m 2 in plan area, a refining tank 3 which is also 150 m 2 in plan area, and a conditioning tank 11 which is 160 m 2 in plan area.
FIGS. 12 and 13 illustrate a continuous glass-melting tank furnace in accordance with this invention.
In the melting compartment 1, batch material is melted by continuously operating side burners 118 whose flames are constrained to lick the surface of the material in the tank by virtue of a lowered portion 116 of the melting tank superstructure. The fuel fed to the burners may be oil or gas. Flames and fumes are then drawn up through chimney 117.
The flow of melt from the melting tank 2 to the refining tank 3 is controlled by a sill 29 in the melting tank and a dropped narrow throat 5 as described with reference to FIG. 4. The sole 23 of the melting tank is at the same level as the soles of the other compartments of the furnace.
In the refining compartment, continuously operating side burners 119, 120, 121 are provided at each side, and fumes and flames are drawn off from the refining compartment through a chimney 122. It is convenient to use gas burners in the refining compartment. The upstream end wall 6 of the refining compartment 4 is oblique. The transverse sill 7 is located so that the mean length of the upstream refining cell is greater than its width. The width of that cell is in turn greater than its depth. The sill occupies some four-fifths of the depth of the melt.
A transverse row of three booster electrodes 33 projects upwardly through the sole of the cell 8 at the neutral line. A second row of booster electrodes may be provided upstream of the first if desired.
Molten refined glass leaving the refining tank 3 passes through the neck 10, into a conditioning tank 11 and thence directly into the drawing tank 123 of a horizontal glass drawing machine.
A specific embodiment of a continuous glass-melting tank furnace designed in accordance with FIGS. 12 and 13 for the production of glass at a rate of 50 tonnes per day has a melting tank 2 which is 20 m 2 (4 m×5 m) in plan area, and a refining tank 3 which is 33 (4 m×8.3 m) m 2 in plan area.
FIG. 14 illustrates a further embodiment of a furnace for the continuous production of molten glass. In FIG. 14, the melting compartment is of the cupola type, in which melting is effected by means of a plurality of vertical electrodes 124 leading through the sole 23 of the melting tank 2 to provide heat energy for melting batch material 125 which is uniformly spread over the surface of the molten material in the tank 2. The melting tank 2 communicates with the refining tank 3 via a dropped throat 5 (compare FIG. 13, though no sill is provided in the melting tank). The design of the refining compartment 4, the neck 10 and conditioning tank is the same as that of the embodiment shown in FIGS. 12 and 13, though the outlet end of the furnace is shown as being provided with a pouring spout 34 for feeding a float chamber or casting machine. | A method for manufacturing glass wherein raw material is fed as a batch to a continuous glass-melting tank furnace, melted in a melting tank and passed to a refining tank via a submerged throat. The melt is heated in the refining tank to de-gas it, and then molten refined glass is delivered to a conditioning tank where it is brought to a desired working temperature. The refining tank is divided into upstream and downstream refining cells by a transverse sill. The melt in the upstream refining cell is heated to create a spring zone located towards the downstream end of that cell and a circulation of melt in that cell which feeds the spring zone. | 2 |
BACKGROUND OF THE INVENTION
[0001] This invention relates to an article of footwear, such as a sandal or other shoe, having a reversible upper system.
DESCRIPTION OF BACKGROUND ART
[0002] Most shoes include an upper and a sole. The upper is commonly fixedly attached to the sole to help retain the foot of the user to the shoe. Such shoe uppers commonly present only a single outward appearance. This limits the potential outward appearances of a shoe. Further, with a single upper presentation system, strains, scratches, and other blemishes may cause the shoe to have an unsightly appearance and render it inappropriate or undesirable for wear. A shoe having a reversible upper system is disclosed in U.S. Pat. No. 2,409,813. However, such a reversibility system has a significant drawback in that it inherently results in an undesirable fit, and exposes ground-contacting sole material directly to the foot of the user.
BRIEF SUMMARY OF THE INVENTION
[0003] The following presents a simplified summary of the invention in order to provide a better understanding of some aspects of the invention. It is not intended to be an extensive overview of the invention or aspects thereof. Nor is it intended to identify or define critical elements of the invention. This summary merely describes some aspects of the invention in a simplified manner as a prelude to the detailed description hereinafter.
[0004] It is an aspect of the invention to provide a pair of shoes having a set of uppers that are removably attachable to sole units. The uppers are reversible such that it will have a first appearance on one sole and a different appearance when inverted and coupled to the other sole. This provides the user with multiple fashion choices for the presentation of his or her shoes.
[0005] An aspect of the present invention is directed to a pair of shoes including a left sole, a right sole, and first and second reversible uppers. The uppers are removably detachable from the left and right soles. Each of the uppers is longitudinally asymmetric.
[0006] Another aspect of the present invention is directed to a pair of shoes including a left sole, a right sole, and first and second uppers each removably detachable from the left and right soles. The pair of shoes further includes a keyed upper-to-sole coupling system for coupling the uppers to the soles such that the first upper can be coupled to the left sole in a first exposed orientation and coupled to the right sole in a second exposed orientation opposite from the first exposed orientation, and wherein the second upper can be coupled to the right sole in a first exposed orientation and coupled to the left sole in a second exposed orientation opposite from the first exposed orientation.
[0007] Another aspect of the present invention is directed to a pair of uppers that are movably attachable to a pair of soles. The uppers include keyed mating coupling elements such that the first upper is attachable to a first sole only in a single exposed orientation and is attachable to the second sole only in a different exposed orientation, and the second upper is attachable to the second sole only in a single exposed orientation and is attachable to the first sole only in a different exposed orientation.
[0008] The various advantages and features of novelty that characterize the present invention are pointed out with particularity in the claims. To gain an improved understanding of the advantages and features of novelty that characterize the present invention, however, reference should be made to the enclosed detailed description and accompanying drawings which describe and illustrate various embodiments of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] FIG. 1 is a top view of a pair of shoes having upper portions being attached to the soles in a first configuration in accordance with the present invention.
[0010] FIG. 2 is a top view of the pair of shoes of FIG. 1 with the upper portions being removed.
[0011] FIGS. 3A and 3B are top and bottom views respectively of an exemplary upper in accordance with the present invention.
[0012] FIG. 4 is a top view of the pair of shoes of FIG. 1 with the upper portions being attached to the soles in a second configuration in accordance with the present invention.
[0013] FIGS. 5 and 6 are front-lateral and front-medial perspective views of the shoe of FIG. 1 with the upper portion being attached to the sole in the first configuration.
DETAILED DESCRIPTION OF THE INVENTION
[0014] In the following description of the various embodiments, reference is made to the accompanying drawings that depict illustrative arrangements in which the invention may be practiced. It is understood that other embodiments may be utilized and modifications may be made without departing from the scope of the present invention. Additionally, various terms used herein are defined below.
[0015] FIGS. 1-6 show an exemplary embodiment of a pair of articles of footwear generally designated with reference number 10 and referred to herein as a pair 10 of shoes 12 . The shoes 12 are preferably, but need not be, sandals such as shown in the figures. The pair 10 of the shoes is shown in FIGS. 1 and 4 and includes a left shoe 12 l and a right shoe 12 r.
[0016] Each shoe 12 l or 12 r in the pair 10 includes a sole 14 and an upper 20 . The sole 14 is intended to provide a wear resistant lower surface and preferably also a suitable amount of cushioning capabilities. The upper 20 holds the user's foot to the sole 14 and provides a fit for the user's foot. The upper 20 includes a back edge or otherwise open area to form a foot opening permitting the insertion of the user's foot into the shoe 12 and onto a footbed 17 . In an exemplary arrangement where the shoe 10 is a sandal, as depicted, the removable upper 20 is a strap system. As will be evident from the following description, each upper/strap system 20 is removably coupled to each sole 14 by an upper-to-sole attachment system that enables the upper 20 to be reversible when transferred from one shoe in the pair (e.g., the left shoe 12 l ) to the other shoe in the pair (e.g., the right shoe 12 r ).
[0017] Additionally, each shoe 12 , upper 20 , and sole 14 includes a medial side and a lateral side. The medial side is the side that faces toward the centerline of the user's body when worn. The lateral side is the side that faces away from the centerline of the user's body when worn. The lateral side of each shoe is designated by reference numeral 13 l , while the medial side of each shoe 12 is designated by reference numeral 13 m . Also, as can be seen in FIG. 2 , the lateral side of each sole 14 is designated by reference numeral 15 l , while the medial side of each sole 14 is designated by reference numeral 15 m . Similarly, the lateral side of each removable upper 20 is designated by reference numeral 21 l , while the medial side of each removable upper 20 is designated by reference numeral 21 m.
[0018] In an exemplary embodiment each sole 14 is formed of any conventional durable material to resist wearing during use, such as but not limited to, rubber and rubber compositions, including phylon. The soles 14 may be formed by a single unitary molded structure. Alternatively, each sole 14 may include a midsole material for cushioning and an outsole. If used, the composition of midsole may be of any desired structure or material, such as compression molded ethylene vinyl acetate (EVA), intended to provide cushioning for the user. Many variations of midsole structures that may be used in the present invention include but are not limited to full length molded designs and discrete portions of cushioning material. Further, if desired, the midsole can include one or more subcomponents such as gas, liquid, or fluid bladders encapsulated in midsole material, and/or vertical column structures. As described hereinafter, the sole 14 also includes coupling elements that form part of an upper-to-sole coupling system. In the depicted embodiment, each sole 14 includes a front medial coupling 52 , a rear medial coupling 54 , a front lateral coupling 56 , and a rear lateral coupling 58 .
[0019] Each upper 20 has two different presentable external surfaces, such as faces 22 i and 22 ii on a central body portion. Based on which sole 14 r or 14 l that upper is attached to, one of the faces 22 i or 22 ii will be exposed at a given time and the other of the faces 22 i and 22 ii will be facing inward toward the foot of the user. FIG. 3 a shows the upper 20 in a first exposed orientation such that first external face 22 i is exposed to provide a first appearance. FIG. 3 b shows the upper 20 in a second exposed orientation, inverted from the first orientation, such that second external face 22 ii is exposed to provide a second appearance. As can be understood, the first external face 22 i and the second external face 22 ii are on opposite sides of the upper. In an exemplary arrangement, as depicted, external faces 22 i and 22 ii have two different appearances. However, one alternative embodiment, not shown, includes the first external face 22 i and the second external face 22 ii having the same appearance.
[0020] The upper 20 may also include, as depicted, a rear trim 24 or covering and a front trim 26 or covering. If desired these sections 24 and 26 may be padded. These sections may serve to protect the main body portion 22 and add increased comfort to the pair of shoes 10 . The material for the upper 20 is not critical to the invention. However, in one configuration, the upper 20 may be made partially or entirely of synthetic materials. For example, the front and rear trim sections 26 and 24 may be made of a synthetic leather material, and the central body region 22 may be made of a woven synthetic material and may include a synthetic coating if desired. However, it is recognized that many other materials may be used in lieu of those described herein.
[0021] The upper 20 also includes extension sections that serve as straps and also extend to a coupling device. These extensions may be part of the central body portion 22 . In the depicted exemplary embodiment, there is a front medial extension 32 , a rear medial extension 34 , a front lateral extension 36 , and a rear lateral extension 38 . A coupling element 42 , 44 , 46 , and 48 is located at or near the end of each respective extension 32 , 34 , 36 , and 38 . As described hereinafter, the coupling elements 42 , 44 , 46 , and 48 of the upper 20 engagingly mate with the coupling elements 52 , 54 , 56 , and 58 of the sole 14 .
[0022] To enhance comfort, each upper 20 is not symmetric about a longitudinal center line of the shoe. That is, the uppers 20 are asymmetric. Specifically, they are longitudinally asymmetric in that the lateral and medial sides are not mirror images about a center line through the approximate center of the shoe. This enables the strap system 20 to better and more comfortably interface with the anatomy of the human foot to enhance the fit of the shoe 12 . While the drawings depict a first exemplary asymmetric strap system 20 , alternative asymmetric strap systems/uppers may be used in lieu of the depicted embodiment.
[0023] The upper-to-sole attachment system includes the removably mating or interfacing couplings on the upper 20 and on the sole 14 . In the illustrated embodiment, the coupling includes an anchor on the sole 14 and a mating hole on the upper 20 . More specifically, and as seen in FIG. 2 , each anchor on the sole 14 includes an outwardly protruding body portion or shank 50 and an enlarged end section or shoulder 51 disposed on the distal end of the body portion 50 . The anchor may be molded integrally with the sole 14 or a portion of the sole 14 . Alternatively, the anchors may be molded separately and be provided with a plug portion 53 that is an extension of the body portion 50 . This is schematically represented in the rear medial portion of the right sole 14 r of FIG. 2 . If the anchors are made separately, the sole 14 may include a channel sized complimentary to the plug portion 53 and the plug portion 53 may be inserted into and glued or otherwise fixed into the channel.
[0024] The mating coupling portion on the upper 20 includes a flange 60 that has a hole 62 therein. The hole is preferably shaped and sized to be slightly larger than, but substantially complimentary to, the body portion 50 of the anchor. The shoulder 51 is similarly shaped but slightly larger than the hole 62 . The shoulder 51 is somewhat flexible to permit the hole 62 to be worked over the shoulder 51 and onto the body portion 50 . Once positioned on the body portion 50 , the flange 60 will remain coupled to the anchor during normal footwear usage until the flange is manually worked back over the flexible shoulder 51 . It is recognized that other complimentary coupling arrangements may be used.
[0025] In the depicted embodiment, the upper-to-sole attachment system is a multiple point attachment system, and includes four attachment points wherein the strap system 20 and the sole 14 can be removably coupled. In the depicted arrangement, there is an attachment point at the front medial, rear medial, front lateral, and rear lateral portions of the shoe. Thus, this respectively corresponds to the coupling elements on the sole 52 , 54 , 56 , and 58 and the coupling elements on the upper 42 , 44 , 46 , and 48 . It is recognized that more or less than four couplings may be used, and they need not be located in each quadrant of the shoe.
[0026] Since the upper 20 is asymmetric, it is helpful to prevent the user from placing the upper 20 on the sole upside-down or angularly displaced. The coupling system is preferably “keyed” to achieve this goal. By keyed, and in the depicted arrangement, it means at least one coupling for the upper 20 does not normally fit or mate with at least one coupling for the sole 14 . Specifically this is achieved in the exemplary depicted embodiment by including two sets of differing couplings for the upper 20 and two sets of differing couplings for the sole 14 . Thus, there are some couplings wherein they will not properly mate with one another. In one arrangement, as shown, one coupling will not fit the remaining coupling. While this can be achieved in different manners, such as having a different size and/or shape, the rear lateral couplings on the sole and on the upper depicted embodiment is differently (e.g., sized larger) than the other three couplings. This will ensure that the user places the upper 20 in one orientation on one sole and in the opposite exposed orientation when attached to the other sole.
[0027] The larger size also serves as a visual indicator so that a user is not likely to attempt to forcibly assembly and possibly break a coupling device while trying to attach an upper to a sole. A second indicator to minimize the likelihood of an incorrect installation is that the spacing between the couplings is different on the medial and lateral sides. Thus for example, the distance between the two couplings on the lateral side D 1 may be smaller than the spacing on the medial side D 2 . This too will inherently aid the user in the proper assembly process.
[0028] As indicated above, the appearance of the upper 20 will preferably be different to give the user additional aesthetic flexibility in the use of the product. Thus, while the surfaces of 22 i and 22 ii are represented by a striped and a checkered pattern respectively, such representations are intended to depict generic different surfaces. For example, one exposed surface could be a solid color while the other surface could be a pattern. Thus, this would be helpful to wear the desired pattern based on the event/location and/or the clothes that the user is wearing. Alternatively, the exposed surfaces 22 i and 22 ii could be two different pastel colors and the user could install the uppers to best match the clothes that the user is wearing. Alternatively, one side could have a mascot or other indicia of a sports team where the opposing side could be a solid or pattern. If desired, both sides could be provided with the same pattern. This would provide the user with flexibility to change the appearance of the shoe if the shoe upper was worn, damaged, and/or blemished.
[0029] While the various features of shoe 12 work together to achieve the advantages previously described, it is recognized that individual features and sub-combinations of these features can be used to obtain some of the aforementioned advantages without the necessity to adopt all of these features. The present invention is disclosed above and in the accompanying drawings with reference to a variety of embodiments. The purpose served by disclosure of the embodiments, however, is to provide an example of the various aspects embodied in the invention, not to limit the scope of the invention. One skilled in the art will recognize that numerous variations and modifications may be made to the embodiments without departing from the scope of the present invention, as defined by the appended claims. | A shoe includes a reversible upper portion. Each shoe in the pair includes a sole and a reversible upper. An attachment system enables the uppers to be removably attachable to the soles in different exposure orientations. The coupling system may include a mating elements on the upper and the sole. The mating elements may be keyed such that one or more mating elements on the upper may only mate with selected respective elements on the sole. This system enables the reversal of the uppers to expose different aesthetic appearances if the uppers have different aesthetics on the top and bottom. As the uppers are preferably designed to be asymmetrical, reversing the uppers is accomplished by detaching and moving the upper from one sole to the other sole, inverting it to expose the other side, and attaching it to the other sole. This is particularly useful for a pair of sandals. | 0 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a novel process for preparing azidomethylthienylacetic acids and certain esters thereof useful in the synthesis of aminomethylthienylmethylpenicillins and aminomethylthienylmethylcephalosporins. The novel azidomethylthienylacetic acids are prepared by oxidative rearrangement of azidomethylthienylmethyl ketones by thallium (III) nitrate in the presence of methanol or ethanol and certain specified acids to provide the methyl azidomethylthienylacetates when methanol is employed or the corresponding ethyl esters when ethanol is used. The azidomethylthienylacetic acids are obtained by hydrolysis of the esters. The azidomethyl compounds provided by the process of the invention are useful intermediates in the preparation of aminomethylthienylmethylpenicillins and -cephalosporins by acylation of 6-APA, 7-ACA or their derivatives to obtain corresponding azidomethylthienylmethyl compounds which are then converted to the analogous aminomethyl compounds by well-known means. British Pat. No. 1,467,407 (Derwent No. 73775V) discloses a similar process employing amino-protected methyl 5-aminomethyl-2-thienyl ketones to provide the corresponding 2-thienylacetic acids. However, the use of methyl azidomethylthienyl ketones is novel and unexpected in view of the prior art which discloses that alkyl azides are unstable to acids such as those employed in the present process.
2. Description of the Prior Art
McKillop et al., J. Am. Chem. Soc., 93, 4919 (1971) has shown that thallium (III) nitrate in methanol containing perchloric acid converts acetophenones into methyl phenylacetates. However, in defining the limitations of this conversion the author points out that the reaction is unsuccessful when applied to compounds containing an amino group due to preferential complexation of the amino substituent with the thallium electrophile. The corresponding amides are stated to react normally. The above-mentioned British Pat. No. 1,467,407 discloses that amino protected 5-aminomethyl-2-thienylacetic acids may be prepared by reaction of amino protected 2-acetyl-5-aminomethylthiophenes with thallium (III) nitrate in the presence of lower alkanols such as methanol and perchloric acid followed by hydrolysis of the intermediate ester. The use of the amino protected 5-aminomethyl-2-thienylacetatic acids or a reactive functional derivative thereof to acylate certain 7-aminocephalosporanic acids and derivatives thereof followed by removal of the amino protecting group to provide the corresponding 7-(5-aminomethyl-2-thienylmethyl)cephalosporins is also described.
U.S. Pat. Nos. 3,966,710 and 3,997,527 disclose a series of aminomethylarylmethylpenicillins, particularly 6-(phenyl- and thienylacetamido)penicillanic acids and esters substituted in the phenyl and thienyl moieties with an aminomethyl substituent. The aminomethylarylacetic acid intermediates employed, including 2-aminomethyl-3-thienylacetic acid and 3-aminomethyl-2-thienylacetic acid were prepared by conventional synthetic methods. The former compound was prepared from 2-aminomethyl-3-methylthiophene by acetylation, free radical catalyzed bromination to obtain N-acetyl-2-aminomethyl-3-bromomethylthiophene; this intermediate was then converted to the 3-cyanomethyl analog which was hydrolyzed to the desired 3-thienylacetic acid. The isomeric 3-aminomethyl-2-thienylacetic acid was obtained from 2-thienylacetamide via the corresponding N-hydroxymethyl compound, cyclization to 3-aminomethyl-2-thienylacetic acid lactam and hydrolysis.
The amino moiety of the aminomethyl substituted arylacetic acids was protected, preferably by reaction with methyl acetoacetate as taught in U.S. Pat. No. 3,813,376, prior to acylation of 6-APA or its esters.
o-Azidomethylphenylacetic acid and methods for its preparation from o-bromomethylphenylacetate esters are disclosed in U.S. Pat. Nos. 3,766,175; 3,813,391; 3,814,755 and 3,840,535. However, the azidomethylthienylacetic acids and esters are not known in the art.
Abramovitch and Kyba in "The Chemistry of the Azido Group", S. Patai, Editor, Interscience Publishing Co., New York, 1971, Chapter 5, pp. 221-239, record that alkyl azides, including aralkyl azides, are unstable in the presence of protonic acids such as sulfuric, hydrochloric, perchloric and trifluoroacetic acids, especially upon warming. Such azides are also reported to be unstable to Lewis acids such as aluminum trichloride and antimony pentachloride.
SUMMARY OF THE INVENTION
It has now been found that novel compounds of the formula: ##STR1## wherein R is hydrogen or R O where R O is methyl or ethyl are obtained by a novel process which comprises the steps of:
(a) contacting approximately equimolar amounts of a ketone of the formula: ##STR2## and thallium (III) nitrate in the presence of at least a molar excess of an alcohol of the formula R O OH and from about 0.1 to 10 moles of acid per mole of said ketone, said acid being a member selected from the group consisting of perchloric, sulfuric, nitric, toluenesulfonic, methanesulfonic, fluosulfonic and fluoboric acids, at a temperature of from about 0° to 80° C. to obtain a product of formula (I) wherein R is said R O ; and
(b) hydrolyzing said product of step (a) under ester hydrolyzing conditions when a compound of formula (I) wherein R is hydrogen is desired.
The process of the invention is unexpected in view of the prior art which teaches that organic azides such as the above azidomethyl group containing reactants and products of the process are unstable to the strong acids employed. The products provided have advantages over aminomethylthienylacetic acids as intermediates in the synthesis of aminomethylthienylmethylpenicillins and -cephalosporins since the azido containing acids or certain carboxyl derivatives thereof known in the art for acylation of penicillins and cephalosporins may be employed directly without protection of the azido group to provide the corresponding azidomethylthienylmethylpenicillins and cephalosporins, and the azido group subsequently converted to an amino group by simple catalytic hydrogenation. The use of aminomethylthienylacetic acid, on the other hand, requires the use of an amino protecting group and subsequent removal thereof from the penicillin or cephalosporin precursor.
It is a further object of this invention to provide the novel compounds of formula (I), especially 2-azidomethyl-3-thienylacetic acid, 3-azidomethyl-2-thienylacetic acid, 5-azidomethyl-2-thienylacetic acid and the methyl and ethyl esters of each.
DETAILED DESCRIPTION OF THE INVENTION
The process of the present invention may be employed to prepare azidomethylarylacetic acids and derivatives thereof of the general formula ##STR3## wherein R is hydrogen or R o where R o is methyl or ethyl; R 1 is hydrogen, methyl or ethyl; R 2 is hydrogen or alkyl having from one to three carbon atoms; and Ar is ##STR4## wherein R 3 is a member selected from the group consisting of hydrogen, F, Cl, Br, hydroxy and alkoxy having from one to three carbon atoms; and R 4 is a member selected from the group consisting of hydrogen, F, Cl and Br; which comprises contacting approximately equimolar amounts of a ketone of the formula ##STR5## and thallium (III) nitrate in the presence of an alcohol, R o OH and in the presence of certain strong acids.
Particularly preferred, however, is the process for the production of the novel azidomethylthienylacetic acids and esters of the formula ##STR6## wherein R is as defined above.
In carrying out the preferred process the appropriate methyl azidomethylthienyl ketone and thallium (III) nitrate are contacted in the presence of methanol or ethanol which has been acidified with certain strong acids. By "strong acid" within the context of this invention is meant an organic or inorganic acid having a pKa of about 2 or lower. Suitable strong acids are those that allow the desired reaction to take place without substantial production of undesirable by-products. While many such suitable strong acids are available in the art, preferred such acids are perchloric, sulfuric, nitric, toluenesulfonic, methanesulfonic, fluosulfonic and fluoboric acids. An especially preferred acid is perchloric acid for reasons of economy and efficiency.
The above-mentioned ketone starting material and thallium (III) nitrate are preferably contacted in equimolar amounts. However, a molar excess of either reactant may be employed if desired. While the amount of alcohol theoretically required is also equimolar, it is preferable to use at least a molar excess of said alcohol, up to about 100 moles per mole of said ketone, such that the alcohol also serves as a solvent for the reaction.
The mole ratio of the preferred strong acid to said ketone may vary over a wide range from about 0.01 to 100 moles of such acid per mole of said ketone. A preferred range of such acid, however, is from about 0.1 to 10 moles per mole of ketone and an especially preferred range is from about 3 to 5 moles of such acid per mole of said ketone.
The preferred range of temperature for the process of Step (a) is from about 0° to 80° C. At temperatures substantially lower than 0° C. the reaction rate is exceedingly slow. Temperatures above about 80° C. for the reaction require the use of pressure equipment and such high temperatures cause excessive amounts of undesirable by-products to be formed. Of course, as one skilled in the art is aware, within the preferred range of temperature the reaction will proceed faster at higher temperatures and more slowly at lower temperatures. Within the preferred range of temperature the reaction ordinarily is substantially complete in from about 0.5 to 50 hours. A particularly preferred temperature is room temperature, i.e., from about 15° to 30° C., at which temperature the reaction is substantially complete within about 2 to 24 hours.
The process of the invention is illustrated by the following reaction sequence employing methyl 2-azidomethyl-3-thienyl ketone and methanol. ##STR7##
Thallium (I) nitrate precipitates from the reaction mixture as a white solid during the reaction. When the reaction of Step (a) is substantially complete the desired azidomethylthienylacetic acid ester is isolated by standard methods well known in the art. For example, the reaction mixture may be filtered to remove precipitated salt, the filtrate concentrated, diluted with water and concentrated again to ensure complete removal of alcohol. The residue is partitioned between water and a water immiscible solvent such as, for example, ethyl ether, chloroform or benzene, and the organic extracts are washed, dried and evaporated to dryness. The crude residual ester may be used in Step (b) or may be further purified, for example by recrystallization or by column chromatography.
The methyl and ethyl esters provided in Step (a) serve as intermediates which are converted to the desired azidomethylthienylacetic acids by hydrolysis in Step (b). The hydrolysis may be carried out under either alkaline or acidic conditions commonly used in the art for ester hydrolysis. When alkaline conditions are employed, the ester is contacted with aqueous base optionally in the presence of a water miscible organic solvent such as ethanol, methanol or acetone. Examples of bases which may be employed are sodium hydroxide, potassium carbonate and calcium hydroxide. The alkaline hydrolysis may be allowed to proceed at room temperature or may be heated at temperatures up to the reflux temperature. The resulting alkali metal or alkaline earth salt of the azidomethylthienylacetate is acidified and the acid isolated by standard means well known in the art.
When acid hydrolysis is employed, it is preferred that the ester obtained in Step (a) is dissolved in a water miscible organic solvent such as, for example ethanol, methanol, acetone, dimethoxyethane, diethylene glycol dimethyl ether or tetrahydrofuran. An especially preferred such solvent is tetrahydrofuran. To this solution is added an aqueous solution of an acid. While any of the acids ordinarily employed for ester hydrolysis will suffice, preferred such acids are sulfuric, phosphoric and hydrochloric acid. Hydrochloric acid is especially preferred for reasons of efficiency. The acidic hydrolysis is preferably carried out at a temperature in the range of from about room temperature up to the reflux temperature of the solvent. Reflux temperature is particularly preferred to shorten the time required for hydrolysis to about 2 to 8 hours.
When the acid hydrolysis is substantially complete, the reaction mixture is cooled and the desired acid isolated by standard methods well known in the art. For example, the reaction mixture is made alkaline with, e.g., sodium hydroxide or potassium carbonate, the alkaline mixture washed with ether to remove neutral organic material, the aqueous layer acidified and re-extracted with ether. The ether extracts are then evaporated to provide the desired azidomethylthienylacetic acid which is of suitable purity for use in acylation of penicillins or cephalosporins. If desired, however, the azidomethylthienylacetic acid may be further purified by standard means such as by column chromatography.
As will be obvious to one skilled in the art, the acidic reaction mixture from Step (a) may be used in Step (b), after separation of precipitated thallium (I) nitrate, without isolation of the ester. For example, the alcoholic filtrate from the Step (a) reaction mixture may be diluted with water and hydrolyzed as described above either with or without addition of one of the acids preferred for hydrolysis.
The azidomethylthienylacetic acids of the invention or the reactive functional carboxyl derivatives thereof may be used to acylate 6-aminopenicillanic acid (6-APA), its esters, including monosilyl and disilyl-6-APA and other derivatives of 6-aminopenam such as, for example, 6-amino-2,2-dimethyl-3-(tetrazol-5-yl)penam which is disclosed in U.S. Pat. No. 4,026,881 and Belgian Pat. No. 821,163. The acids of formula (I) can likewise be used to acylate 7-aminocephalosporanic acids such as, for example, those of British Pat. No. 1,467,407; U.S. Pat. Nos. 3,766,175; 3,766,176 and 3,814,755, as well as other 7-aminocephem derivatives, for example the 4-(tetrazol-5-yl)-3-cephems of U.S. Pat. No. 3,966,719.
The acylation methods which may be used to provide the above-mentioned azidomethylthienylacetamidopenams and -cephems are well known in the art. For example, the free acids of formula (I) may be employed directly for acylation of the above mentioned 6-aminopenams and 7-aminocephems, in which case a suitable condensing agent, e.g., N,N'-dicyclohexylcarbodiimide, is also employed; or the acid of formula (I) may first be converted into a reactive functional carboxyl derivative, e.g., the acid chloride, acid bromide or mixed anhydride with the ethyl half-ester of carbonic acid which is then condensed with the 6-aminopenam or 7-aminocephem. These and other well known acylation methods which may be employed are described in, e.g., U.S. Pat. Nos. 3,966,719; 4,024,249; Belgian Pat. No. 821,163; British Pat. No. 1,467,407 and Ekstrom et al., Acta. Chem. Scand., 19, 281-299 (1965).
While the azidomethylthienylacetamidopenicillins and corresponding cephalosporins are themselves valuable antibacterial agents, they preferably serve as intermediates to provide the more potent antibacterial aminomethylthienylacetamidopenicillins and cephalosporins such as, for example, those disclosed in U.S. Pat. No. 4,009,160 and British Pat. No. 1,467,407. The azido group is conveniently converted to an amino group by catalytic hydrogenation, while the hydrogenation may be carried out employing any of the catalysts and conditions known to those skilled in the art, it is preferred to employ a palladium catalyst. The palladium catalyst may be supported on, for example, activated carbon or calcium carbonate or may be unsupported palladium powder or palladium formed in situ by reaction of a palladium oxide or salt with hydrogen.
The hydrogenation may be carried out under a wide range of temperature and pressure conditions. However, temperatures in the range of about 0° to 100° C. and especially about 25° to 50° C. are preferred. Preferred pressures for the hydrogenation are from about atmospheric pressure to 5 atmospheres. The hydrogenation is carried out in the presence of a reaction-inert solvent such as, for example, water, ethanol, methanol, tetrahydrofuran, dioxane or mixtures thereof. Ordinarily, the azidomethyl group containing compound dissolved in said solvent is mixed with catalyst, adjusted to a pH of about 6-8 and hydrogenated in a suitable apparatus well known to those skilled in the art. When hydrogen uptake is substantially complete, the catalyst is removed by filtration and the desired aminomethylthienylacetamidopenicillin or -cephalosporin isolated by standard methods, such as, for example, precipitation at the isoelectric point or acidification and extraction into a suitable water immiscible solvent, for example, chloroform or ethyl ether. The isolated antibacterial compound may be purified, if desired, for example, by column chromatography.
Preparation of Starting Materials
2-Acetyl-3-methylthiophene and 2-acetyl-4-methylthiophene are prepared by acetylation of commercially-available 3-methylthiophene with acetic anhydride in the presence of phosphoric acid by the procedure of Hartough and Kosak, J. Am. Chem. Soc., 69, 3093 (1974). Using the same procedure with commercial 2-methylthiophene provides 2-acetyl-5-methylthiophene.
3-Acetyl-2-methylthiophene is obtained by acetylation of 2-thenyl-magnesium chloride by the method of Gaertner, J. Am. Chem. Soc., 73, 3934 (1951). 3-Acetyl-4-methylthiophene is provided by the following reaction sequence: ##STR8## The chlorination step is carried out by the method of Campaigne and LeSuer, J, Am. Chem. Soc., 71, 333 (1949). The acetylation step is carried out in a hydrocarbon solvent in an inert atmosphere. The dehalogenation to provide the desired intermediate is carried out employing a palladium-on-calcium carbonate catalyst by well-known means; see, for example, Freifelder, "Practical Catalytic Hydrogenation", John Wiley and Sons, Inc., New York, 1971.
4-Acetyl-2-methylthiophene is prepared by the reaction of 2-methylthiophene-4-carboxylic acid [Shvedov et al., Khim. Geterotsikl. Soedin., 1010 (1967); Chem. Abstr., 69, 51922j (1968)] with methyl lithium or by reacting the corresponding acid chloride with lithium dimethylcopper or dimethyl cadmium. The acetyl methylthiophenes are converted to the requisite azidomethylthienylmethyl ketones as outlined below for 3-azidomethyl-2-thienylmethyl ketone. ##STR9## The thienyl bromides are obtained by reacting equimolar amounts of the acetyl methylthiophene and N-bromosuccinimide (NBS) and a catalytic amount of α,α-azobisisobutyronitrile (AIBN) in carbon tetrachloride. The mixture is heated at reflux, typically for about 4 hours, and worked up by methods well known to those skilled in the art. The thenyl bromides obtained are reacted with an equimolar amount of sodium azide in aqueous acetone. This step is ordinarily carried out at room temperature for about 2 to 4 hours and the desired product isolated by standard procedures well known in the art.
The following examples are provided to further illustrate the invention. However, they are not to be construed as limitations of this invention, many variations of which are possible without departing from the spirit or scope thereof. In the examples the following abbreviations are used: 1 H NMR for Proton Nuclear Magnetic Resonance Spectra, s for singlet, d for doublet, q for quartet, IR for infrared.
EXAMPLE 1
Methyl 3-Azidomethyl-2-thienylacetate
To a solution of methyl 3-azidomethyl-2-thienyl ketone (20.5 g., 0.113 mole) in 230 ml. of methanol and 46 ml. of 70% aqeuous perchloric acid, was added 55.1 g. (0.124 mole) thallium (III) nitrate trihydrate. A white precipitate of thallium (I) salts soon formed. The resulting mixture was stirred at 20°-25° C. for 24 hours. Sodium chloride, 10.5 g., was added, the suspension stirred for 15 minutes and then filtered. The filtrate was evaporated in vacuo to about half volume, 150 ml. of water was added and the solution evaporated again to remove the remaining methanol. The resulting mixture was diluted with water and extracted three times with 200 ml. portions of diethyl ether. The combined extracts were washed with saturated sodium chloride solution, saturated sodium bicarbonate solution till basic, dried over magnesium sulfate and evaporated to dryness. The residue was filtered through a 1-inch layer of Florisil, washing with chloroform, and the filtrate evaporated to obtain the desired product as an oil, 17.2 g. (72% yield). 1 H--NMR (CDCl 3 ), ppm. (δ): 7.22 (d, J=5, aromatic-H), 7.0 (d, J=5, aromatic-H), 4.35 (s, CH 2 N 3 ), 3.8 (s, CH 2 ), 3.7 (s, OCH 3 ); IR spectrum (film), cm. -1 : 3100, 2100 (N 3 ), 1740 (CO 2 CH 3 ).
EXAMPLE 2
Ethyl 3-Azidomethyl-2-thienylacetate
When an equal volume of ethanol is employed to replace the methanol used in Example 1 and the reaction mixture is heated at reflux for 1 hour then worked up as described in Example 1, the title compound is obtained.
When the above reaction in ethanol is carried out at 0° C. for 3 days the results are substantially the same.
EXAMPLE 3
Methyl 5-Azidomethyl-2-thienylacetate
When the procedure of Example 1 was repeated but employing an equivalent amount of 5-azidomethyl-2-thienylmethyl ketone in place of the 3-azidomethyl isomer used therein, the title compound was obtained as an oil in 53% yield. 1 H--NMR (CDCl 3 ), ppm. (δ): 7.6-6.8 (m, aromatic-H), 4.50 (s, CH 2 ), 3.85 (s, CH 2 ), 3.75 (s, OCH 3 ); IR spectrum (film), cm. -1 : 2950, 2100, 1740, 1450.
EXAMPLE 4
Ethyl 2-Azidomethyl-3-thienylacetate
Methyl 2-azidomethyl-3-thienyl ketone (18.1 g., 0.10 mole) is dissolved in a mixture of 180 ml. of ethanol and 1.0 g. (0.01 mole) of concentrated sulfuric acid. Thallium (III) nitrate trihydrate (44.4 g., 0.10 mole) is added and the mixture is heated at reflux for three hours and allowed to stand overnight at room temperature. The precipitated salt is removed by filtration, the filtrate concentrated in vacuo to a small volume, 125 ml. of water added and the solution again evaporated to a small volume. The resulting residue is partitioned between water and ethyl ether, and the combined ether extracts washed with saturated brine, then saturated sodium bicarbonate solution and dried over magnesium sulfate. The crude title compound is obtained upon evaporation of solvent. Further purification, when desired, is obtained by chromatography on Florisil or Sephadex LH-20.
EXAMPLE 5
When the procedure of Example 4 is repeated, but employing the acid catalyst, reaction temperature and times indicated below, ethyl 2-azidomethyl-3-thienylacetate is similarly obtained.
______________________________________ Mole Ratio ReactionAcid Catalyst Acid Cat./ketone Temp. ° C. Time,Hrs.______________________________________H.sub.2 SO.sub.4 5 50 8HClO.sub.4 10 15 24p-Toluenesulfonicacid, hydrate 3 80 1CH.sub.3 SO.sub.3 H 10 80 0.5FSO.sub.3 H 1 25 30HBF.sub.4 0.1 30 50HNO.sub.3 5 0 50______________________________________
EXAMPLE 6
Methyl 2-Azidomethyl-4-thienylacetate
Methyl 2-azidomethyl-4-thienyl ketone (9.05 g., 0.05 mole), 150 ml. of methanol, 12.0 g. (0.15 mole) of 70% nitric acid and 22.2 g. (0.05 mole) of thallium (III) nitrate trihydrate is heated at reflux for 2 hours, cooled to room temperature, neutralized with dilute sodium hydroxide solution, filtered and the filtrate worked-up as described in Example 4 to obtain the title compound.
EXAMPLE 7
Methyl 4-Azidomethyl-2-thienylacetate
When the procedure of Example 1 is repeated, but employing methyl 4-azidomethyl-2-thienyl ketone as starting material in place of the methyl 3-azidomethyl-2-thienyl ketone used therein, the title compound is obtained in like manner.
EXAMPLE 8
Methyl 4-Azidomethyl-3-thienylacetate
When the procedure of Example 1 is repeated but employing methyl 4-azidomethyl-3-thienyl ketone as starting material in place of the methyl 3-azidomethyl-2-thienyl ketone used therein, the title compound is similarly obtained.
EXAMPLE 9
3-Azidomethyl-2-thienylacetic Acid
Methyl 3-azidomethyl-2-thienylacetate (15.6 g., 0.074 mole) was dissolved in 200 ml. of tetrahydrofuran and 30 ml. of 3M hydrochloric acid was added. The solution was heated at reflux for 5 hours, then cooled and adjusted to pH 10 with 10% (by weight) sodium hydroxide solution. The alkaline mixture was washed with 3 × 250 ml. of diethyl ether, the aqueous layer adjusted to pH 2 and extracted with 3 × 250 ml. of the same solvent. The combined ether extracts were dried and evaporated to dryness to obtain 10.5 g. (72% yield) of the desired acid as a solid. 1 H--NMR (CDCl 3 ), ppm. (δ): 9.35 (broad singlet, CO 2 H), 7.15 (d, J=5, 2 aromatic-H), 4.35 (s, CH 2 N 3 ), 3.85 (s, CH 2 CO 2 --); IR spectrum (CHCl 3 ), cm. -1 : 2100, 1700, 1400, 1250, 860, 700.
Hydrolysis of ethyl 3-azidomethyl-2-thienylacetate by the above procedure or by employing an equal volume of 6M sulfuric acid or 8M phosphoric acid in place of the 3M hydrochloric acid also affords the title compound.
When 0.05 mole of methyl 3-azidomethyl-2-thienylacetate is refluxed for two hours in a mixture of 200 ml. of methanol and 15 ml. of 5N sodium hydroxide, then 100 ml. of water added, the alcohol evaporated in vacuo, the residue acidified and extracted with ether, 3-azidomethyl-2-thienylacetic acid is similarly obtained.
EXAMPLE 10
5-Azidomethyl-2-thienylacetic Acid
Methyl 5-azidomethyl-2-thienylacetate (21.1 g., 0.10 mole) was dissolved in 300 ml. of tetrahydrofuran and 40 ml. of 3M hydrochloric acid was added. After heating at reflux for 6 hours the reaction mixture was cooled and the product isolated as described in Example 9 to obtain a 62% yield of oil. 1 H--NMR (CDCl 3 ), ppm. (δ): 9.0 (s, COOH), 6.85 (s, 2 aromatic-H), 4.4 (s, CH 2 N 3 ), 3.75 (s, CH 2 COO); IR spectrum (neat, cm. -1 : 3000 (broad), 2100 (N 3 ), 1710 (CO 2 H), 1680 and 1475.
EXAMPLE 11
Hydrolysis of the methyl and ethyl esters provided in Examples 4 to 8 under the conditions indicated below in each case similarly provides the following azidomethylthienylacetic acids.
__________________________________________________________________________ Acid Temp., Time, Product Solvent* Catalyst ° C. Hrs.__________________________________________________________________________ ##STR10## THF 6M HCl 50 8 ##STR11## ethanol 2M H.sub.2 SO.sub.4 78 4 ##STR12## CH.sub.3 OCH.sub.2 CH.sub.2 OCH.sub.3 5M H.sub.3 PO.sub.4 82 3 ##STR13## methanol 6M H.sub.2 SO.sub.4 50 18 ##STR14## THF 3M HCl 65 6 ##STR15## Diglyme 3M H.sub.2 SO.sub.4 100 2 ##STR16## THF 6M HCl 65 2__________________________________________________________________________ *THF is tetrahydrofuran; Diglyme is diethylene glycol dimethyl ether.
EXAMPLE 12
6-(3-Azidomethyl-2-thienylacetamido)penicillanic Acid
6-Aminopenicillanic acid (4.93 g., 0.023 mole) was dissolved in a mixture of 100 ml. each of water and tetrahydrofuran, adjusted to pH 7.5 with 10% aqueous sodium hydroxide solution and cooled to 0° C. At this temperature was added 3-azidomethyl-2-thienylacetic acid (4.5 g., 0.023 mole) followed by 4.4 g. (0.023 mole) of 1-ethyl-3-(3-diemthylaminopropyl)carbodiimide hydrochloride. The pH of the mixture was adjusted to 5.8 and maintained at 0° to 5° C., pH 6.0-6.1 for 3 hours, adding 3N hydrochloric acid as required. The tetrahydrofuran was removed by evaporation in vacuo, the aqueous residue adjusted to pH 8 and washed with ethyl acetate. The aqueous phase was acidified (pH 2.0) and extracted with 3 × 50 ml. of ethyl acetate. The combined extracts were dried over sodium sulfate and evaporated in vacuo to obtain 5.7 g. (63%) of the title compound as a foamed solid; 1 H--NMR (CDCl 3 ), ppm (δ): 7.8 (d, NH), 7.1 (q, 2 aromatic-H), 3.8 (s, CH 2 ), 1.5 [2s, C(CH 3 ) 2 ]; IR spectrum (KBr), cm -1 : 2105 (N 3 ), 1786 (β-lactam). The compound was found to have an in vitro minimum inhibitory concentration (MIC) vs. Step. pyogenes 1.56 μg./ml.
EXAMPLE 13
6-(3-Aminomethyl-2-thienylacetamido)penicillanic Acid
6-(3-Azidomethyl-2-thienylacetamido)penicillanic acid, 1.97 g., was dissolved in 3 ml. of dioxane and 100 ml. of water was added. To the resulting aqueous solution, 0.8 g. of 10% palladium on carbon catalyst was added, the mixture adjusted to pH 6 and hydrogenated with shaking at 45 p.s.i. (3.16 kg./cm 2 ). At 15 minute intervals the mixture was adjusted to pH 6 with 3N hydrochloric acid. When hydrogen uptake was complete the catalyst was removed by filtration, the filtrate adjusted to pH 5.5 and freeze-dried to obtain 1.48 g. (80%) of the desired product. A portion was purified by column chromatography on Sephadex LH-20, eluting with distilled water; M.P. 195°-215° C. (dec.); 1 H--NMR (D 2 O) 7.4 (q, 2-aromatic H), 5.5 (m, 2H, 5 and 6 position), 4.3 (s, CH 2 ), 4.0 (s, CH 2 ), 1.65 (s, CH 3 ), 1.5 (s, CH 3 ); IR spectrum (KBr),, cm -1 : 1786, 1666, 1600; in vitro minimum inhibitory concentration (MIC) vs. Strep. pyogenes ≦0.1 μg./ml.
PREPARATION A
Acetyl Thenylbromides
i. Methyl 3-Bromomethyl-2-thienyl ketone
A mixture of methyl 3-methyl-2-thienylketone (14 g., 0.10 mole), N-bromosuccinimide (18 g., 0.10 mole), α,α-azobisisobutyronitrile (AIBN, 0.3 g.), and carbon tetrachloride (300 ml.) was heated cautiously to reflux under a nitrogen atmosphere. After stirring 4 hours at reflux, the mixture was cooled, filtered to remove succinimide, washed first with sodium bicarbonate solution, then with saturated sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was evaporated at reduced pressure to obtain a pale yellow solid which was recrystallized from hexane to obtain 16 g. (73%) of the desired product as colorless crystals, M.P. 62°-64° C. 1 H--NMR (CDCl 3 ), ppm. (δ): 7.5 (d, J=5, aromatic-H), 7.2 (d, J=5, aromatic-H), 4.9 (s, CH 2 Br) and 2.55 (s, CH 3 ). This compound is a strong irritant.
ii. Methyl 5-Bromomethyl-2-thienyl ketone
Employing methyl 5-methyl-2-thienylketone as starting material in the above procedure provided the title compound in 70% yield, M.P. 58°-59° C. 1 H--NMR(CDCl 3 ), ppm (δ): 7.5 (d, J=4, aromatic-H), 7.1 (d, J=4, aromatic-H), 4.65 (s, CH 2 Br), 2.55 (s, CH 3 ).
iii.
Employing the appropriate acetylmethylthiophene in the above procedure the following compounds are similarly obtained:
methyl 2-bromomethyl-3-thienyl ketone
methyl 2-bromomethyl-4-thienyl ketone
methyl 4-bromomethyl-2-thienyl ketone
methyl 4-bromomethyl-3-thienyl ketone.
PREPARATION B
Methyl Azidomethylthienyl Ketones
i. Methyl 3-Azidomethyl-2-thienyl Ketone
To a solution of methyl 3-bromomethyl-2-thienyl ketone (5 g., 0.023 mole) in 42 ml. of acetone and 4 ml. of water was added sodium azide (1.56 g., 0.024 mole) with caution (exothermic!). The resulting solution was stirred at room temperature for 2.5 hours, the acetone evaporated, the residue diluted with water and extracted with diethyl ether. The combined extracts were washed with water, saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over magnesium sulfate and the dried extracts evaporated to dryness to obtain 4.0 g. (97%) of yellow oil. 1 H--NMR (CDCl 3 ), ppm. (δ): 7.5 (d, J=5, aromatic-H), 7.2 (d, J=5, aromatic-H), 4.75 (s, CH 2 N 3 ), 2.5 (s, CH 3 ); IR spectrum (film, cm. -1 : 3100, 2100 (N 3 ), 1660, 1525 and 1420.
ii. Methyl 5-Azidomethyl-2-thienyl Ketone
Employing methyl 5 -bromomethyl-2-thienyl ketone as starting material in the above procedure, the title compound was obtained in 94% yield as an amorphous solid. 1 H--NMR (CDCl 3 ), ppm. (δ): 7.6 (d, J=4, aromatic-H), 7.1 (d, J=4, aromatic-H), 4.6 (s, CH 2 ), 2.5 (s, CH 3 CO); IR spectrum (CHCl 3 ), (cm -1 ): 3000, 2975, 2870, 2100, 1675, 1460 and 1370.
iii.
Employing the appropriate methyl bromomethylthienyl ketone selected from those provided in Preparation A, part iii, the following compounds are obtained in a like manner:
methyl 2-azidomethyl-3-thienyl ketone
methyl 2-azidomethyl-4-thienyl ketone
methyl 4-azidomethyl-2-thienyl ketone
methyl 4-azidomethyl-3-thienyl ketone.
PREPARATION C
Methyl-4-methyl-3-thienyl Ketone
i. Methyl 2,5-Dichloro-4-methyl-3-thienyl Ketone
To a solution of 56.6 g. (0.315 mole) 2,5-dichloro-3-methylthiophene [prepared by the method of Campaigne and LeSeur, J. Am. Chem. Soc., 71, 333 (1949)] and 43.6 ml. (0.614 mole) of acetyl chloride in 165 ml. of petroleum ether under a nitrogen atmosphere was added 48 g. (0.36 mole) of anhydrous aluminum chloride. The mixture was stirred overnight at room temperature, then poured onto ice and extracted with ethyl ether. The combined organic layers were dried, evaporated to dryness and distilled at reduced pressure to yield 49 g. (74%) of the dichloroketone, boiling at 74°-78° C. (0.1 mm.); 1 H--NMR (CDCl 3 ), ppm. (δ): 2.6 (s, CH 3 ), 2.25 (s, CH 3 CO).
ii.
A solution of 26.4 g. (0.126 mole) of methyl 2,5-dichloro-4-methyl-3-thienyl ketone in 180 ml. of ethanol is mixed with 5 grams of 10% palladium-on-calcium carbonate and hydrogenated at 3-4 atmospheres hydrogen pressure in a Parr hydrogenation apparatus until hydrogen uptake is complete. The catalyst and salts are removed by filtration and the filtrate evaporated to dryness in vacuo to obtain the title compound.
PREPARATION D
Methyl 2-Methyl-4-thienyl Ketone
2-Methylthiophene-4-carboxylic acid (14.2 g., 0.1 mole) prepared by the method of Shvedov et al., Khim. Geterotsikl. Soedin. 1010 (1967); Chem. Abstrs., 69, 51922j (1968) in 250 ml. of ethyl ether is cooled to -10° to 0° C. and an ethereal solution of methyl lithium (4.4 g., 0.2 mole) is added dropwise while maintaining the reaction mixture below 0° C. After stirring for 1 hour at 0° C., a solution of 4 g. of water in 100 ml. of ethanol is added cautiously and the mixture allowed to warm to room temperature. The desired product is then isolated by partitioning the reaction mixture between ether and water and evaporation of the organic extracts. | Azidomethylarylacetic acids and derivatives thereof are prepared by oxidative rearrangement of the corresponding azidomethylarylmethyl ketones effected by thallium (III) nitrate in the presence of methanol or ethanol and certain acids to obtain methyl or ethyl esters of the desired azidomethylarylacetate. When desired, the acids are obtained by hydrolysis of said esters. The azidomethylarylacetic acids are valuable intermediates in the preparation of aminomethylarylmethylpenicillins and aminomethylarylmethylcephalosporins. | 2 |
CROSS-REFERENCE TO A RELATED APPLICATION
A more detailed explaination of the ground support system set forth herein will be found in my copending case, assigned to the same assignee, entitled "Ground Support System for a Grass Cutting Machine", U.S. Ser. No. 259,485, filed Apr. 30, 1981.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a rotary grass-cutting machine, capable of both cutting grass and trimming lawn edges, employing a flexible strip-like cutting blade carried by a disc, which can be deflected within the disc when the blade strikes a stone or hard object without deflecting the stone, or otherwise disturbing the machine. Also the flexible strip-like blade is angled to produce a vortex effect that aids in both cutting and removal of the blades of grass.
2. Description of the Prior Art
Conventional rotary grass-cutting machines use a fixed blade which is driven by a motor, the leading edge of which provides a cutting edge. When such a blade strikes a hard object, such as a stone, the hard object is deflected and may become mobile creating the possibility of damage to the operator, the blade, or the machine.
The feature of flexibility has been attempted in the prior art at various points and in various ways. Some of the prior art patents teach flexible blades, or flexible blade mountings and/or retractable blade mountings, but for one reason or another none of the prior art attempts have been completely satisfactory. Examples of the prior art attempts can be found in U.S. Pat. Nos. 3,104,510; 3,320,733; 3,343,351; 4,065,913; British Pat. No. 1,237,307; and German Patent Publication (Auslegeschrift) 1,657,039.
SUMMARY OF THE INVENTION
The invention employs a flexible strip-like cutting member supported by a disc within a housing of a rotary-type grass cutting machine. The strip-like member is wound vertically about the disc and the housing has a slope such that the strip-like member is rotated, or twisted, as it extends from the disc beyond the housing so that it has a horizontal leading cutting edge and an inclined trailing edge. This ensures that the strip-like member, as it is driven by a motor in the housing and rotates in the horizontal plane, not only cuts the grass, but creates a vortex which aids cutting by straightening the individual blades of grass.
The disc is indexed to permit the operator to withdraw measured lengths of the cutting strip. A recess is formed in the disc adapted to receive the cutting strip, which is a flexible plastic material, upon the strip being deflected by a heavy obstacle, such as a stone, or the like.
When the cutting blade becomes frayed, the operator withdraws a new piece of the strip from the disc and cuts the used portion. To replace a spent disc, a cover plate on the bottom of the machine is removed and a new disc having a wound strip thereon is mounted on the cover plate after the spent disc has been removed.
One object of the present invention is to provide an improved grass-cutting machine of the rotary type which overcomes the prior art disadvantages; which is simple, economical, and reliable; which uses a cutting blade that is flexible and can be deflected into a recess in the disc whenever the blade strikes a heavy obstacle; which blade is angled to create a vortex for aiding in the cutting and removal of the grass; which uses a flexible strip-like cutting blade having a stored portion and a cutting portion with only the cutting portion extending from the disc; which blade can be deflected if it strikes a hard object; and which cutting blade can be easily replaced when frayed or dull.
Other objects and advantages of the present invention will be apparent from the description of the following illustrative embodiment. The novel features of the invention are pointed out in the claims.
BRIEF DESCRIPTION OF THE DRAWINGS
An illustrative embodiment of the present invention will be described in connection with the accompanying drawings in which:
FIG. 1 is a side elevational view of a grass-cutting machine according to the present invention;
FIG. 2 is an elevational view of the disc, including carrying the strip-like cutting blade in relation to grass, graphically showing the effects of the vortex;
FIG. 3 is a bottom plan view of the disc;
FIG. 4 is a bottom plan view of the disc with the cover partially in section to show the hub carrying the wound storage of the strip-like cutting blade, and the deflection pocket of the cover;
FIG. 5 is an enlarged sectional view taken along lines 5--5 of FIG. 4, showing the indexing and blade storage;
FIG. 6 is a sectional view taken along lines 6--6 of FIG. 4, showing the twisting of the cutting portion of the blade;
FIG. 7 is an end view taken along the lines 7--7 of FIG. 6, showing the angle at which the blade extends from the slot of the cover.
DESCRIPTION OF THE PREFERRED EMBODIMENT
In the illustrated embodiment of the invention a grass cutting machine 10, of the rotary type, is shown in FIG. 1. The machine 10 has a housing 12 in which is mounted a suitable power source such as an electric motor 14, though an internal combustion engine could also have been used. The motor 14 drives a plastic strip-like cutting blade 16 carried on a disc 18 via a belt-drive including a belt 20 driven by a pulley 22 on shaft 24 of motor 14. Belt 20 drives a pulley 26 mounted on a shaft 28 which rotates the disc 18. The blade 16 prescribes a cutting circle 27 shown in dotted line representation in FIG. 3, which lies in a plane 29 shown in FIGS. 1 and 2.
The housing 12 has a deck 30 which extends outwardly from the bottom of a central motor portion 32 thereof in the form of a substantial rectangle having a stepped inset 34 at opposite rear corners thereof, and a arcuate edge 36 centrally disposed at the front end thereof in superposition to the disc 18. Rear wheels 38 are separately disposed to nest in the insets 34 of the deck 30 so as to provide a smooth side profile while extending slightly beyond the rear edge thereof. Each of the wheels 38 are journaled by an axle 40 affixed to the housing 12 inwardly of the inset 34 of the deck 30 and above the cutting plane 29. A handle 42 is connected to the rear of the motor portion 32 of the housing 12 above the deck 30 thereof and central to the wheels 38. The handle 42 will guide the machine 10 over the cutting surface and will be manipulated by the operator so as to cause either of the wheels 38 to act as pivot points in steering the machine 10.
A roller 44 is connected to the housing 12 and extends under the disc 18 at the front edge of the deck 30 for a length substantially corresponding to that of the arcuate edge 36. The roller 44 has a width which greatly exceeds its diameter. The roller 44 is journaled as shown in FIG. 1 by the free end of a support leg or bracket 48 which extends inwardly thereof from opposite ends. The roller 44 is mounted below the cutting plane 29 and within the cutting circle 27. The bracket 48 is substantially "L" shaped and may be in the form of a bent rod of substantially circular cross section, and which section is of small diameter so that only a very small surface area is present along its exposed length to prevent the build-up of grass clippings thereon. Each of the brackets 48 are secured to the housing 12 as shown in FIG. 1 by a bolt 52 threadedly received in a tapped hole in the housing 12. The brackets 48 will be secured to opposite front corners of the deck 30 of the housing 12.
Though the roller 44 is of a small diameter in comparison to the wheel 38, the extensive width of the roller 44 provides a wide foot path which will not interfere with the blades of grass to be cut in that it is completely within the cutting swath 27. The mounting of the roller 44 permits it to lie underneath the cutting blade 16 and disc 18 so as not to interfere with the normal cutting operation thereof. Also, this will permit the blade 16 to extend from both the front and opposite sides of the deck 30 to provide improved visibility of the cutting swath 27 at such locations. The ground support provided by the three point system of the front roller 44 and the two rear wheels 38 is very stable in that it keeps the machine 10 in contact with the ground to a level cut corresponding to the cutting plane 29 over a wide range of ground conditions.
The disc 18 includes a hub 54 and a cover 56 which is secured to the shaft 28 by a nut 58 as shown in FIGS. 1 and 3. Removal of the nut 58 permits the cover 56 to be removed in order to replace the hub 54 upon which has been wound one or more of the cutting strips 16 with two strips 16 being shown in the present embodiment as is best seen in FIG. 4. The cover 56 may be suitably slotted as at 60 as shown in FIGS. 2, 3 and 4 to permit egress of the cutting strip 16 as will be more fully explained hereinafter.
The cutting blade 16 has a cutting portion 62 which is the free end thereof extending from the stored portion 64 wound about the hub 54 and from which it extends outwardly from the disc 18 a short predetermined length to terminate at the cutting circle 27. In the preferred embodiment a pair of cutting blades 16 are used which are double wound upon the hub 54 to individually exit from diametrically formed slots 60. Since the pair of cutting blades 16 and associated disc 18 components such as slots 60 are the same each will be given the same reference character, but reference to either one will equal reference to the pair. As the cutting portion 62 of the blade 16 exits through slot 60 it is twisted as shown in FIGS. 2, 4, 6 and 7 so that the leading edge 66 is closest to the ground and the width is sloped rearwardly and upwardly to the trailing edge 68 at a predetermined angle set by the width of the blade 16 and the height of the slot 60. The twisted blade 16, as it rotates, produces a vortex or fan effect as shown in FIG. 2 urges the blades of grass to be more vertical for cutting thereof, thus the vortex effect aids in cutting and will also aid in removal of the cuttings.
FIGS. 3, 4 and 5 illustrate the arrangement of the cutting assembly 70 and includes the disc 18. The drive member 28 has a flange 72 formed inwardly of its reduced diameter threaded end 74. The disc 18 of the cutting assembly 70 is affixed to the drive member 28 between the flange 72 and a washer 76 by plastic nut 78 threadedly secured to the end 74. Also a "D" flat 80 is formed on the section of the drive member 28 between the flange 72 and the end 74 to engage a complementary surface of a central aperture 82 of the cover member 56 of the disc 18, thereby preventing relative rotation between the disc 18 of the cutting assembly 70 and drive member 28.
FIGS. 3, 4 and 5 also show the relationship of the cutting assembly 70, which includes the disc 18 and the components thereof including, a hub 54 containing the double-wrapped stored portion 64 of the resilient cutting blade 16, and indexing means 84. The top 86 of the hub 54 is flush with the disc's cover member 56 upper surface 88 as best seen in FIG. 6. A sliding clearance exists between the hub's lower surface 90 and the cover member 56. This aids in the operator releasing a predetermined length of the cutting portion 62 of the blade 16 and permits rotation of the hub 54 relative to the cover member 56. The indexing means 84 is connected to member 56 to normally prevent the hub 54 from relative rotation. The indexing means 84 shown in FIGS. 3 and 5 includes a curved spring flap 92 mounted within a lower recessed portion 94 and affixed therein by fasteners 96. A conical projection 98 is connected to the flap's free end and passes through an opening 100 in the cover member 56 to be engaged into one of a plurality of indexing openings 102 in the hub 54. A finger indentation 104 is formed in the recessed portion 94 as shown in FIG. 3, to assist the operator in grasping the indexing means 84 to release the same. The lower recessed portion 94 shelters the connecting means 58 and the indexing means 84.
The cutting blade 16 is constructed of super-tough fast-molding nylon thermoplastic having low notch sensitivity, one such material is sold by DUPONT under the trademark "ZYTEL" ST. The tape is approximately one millimeter thick and eight millimeters wide.
With particular attention to FIGS. 4 and 6, a periphery or circular exterior wall 106 and the circular interior wall 108 enclose an open-topped perimeter cavity 110 in the cover member 56 of the disc 18. This construction conserves material, thereby reducing weight and energy consumption. The base 112 of the disc 18 turns vertically upwardly to terminate at the periphery 106 thereof.
A guide chamber 114 is in communication with the slot 60. The guide chamber 114 is separated from the open chamber 110 by a radial wall 116 and a tangential wall 118. An opening 120 is formed at the base of chamber 114 adjacent the location from which the walls 116 and 118 diverge. The cutting portion 62 exits the hub 54 through the opening 120, the chamber 114 and the slot 60.
Referring to FIGS. 6 and 7, it will be seen that the height of the slot 60 being shorter than the width of the blade 62 acts to orientate the leading edge 66 of the cutting portion 62 of the blade 16 at an angle of attack with respect to the ground surface 18, preferrably within the range of 5° to 15° to provide a suitable vortex effect.
The arrow 122 shown in FIG. 4 indicates that the direction of rotation when viewing the machine 10 downwardly from a top plan view will be counterclockwise, and that the chamber 114 is formed behind the external cutting portion 62 of the blade 16. The cutting portion 62 is of predetermined length and will be set by manual or automatic cut off means (not shown) used by the operator or mounted in the housing 12 on the underside of the deck 30 thereof. The length of the slot is greater than the external length of the cutting portion 62. The blade 16 is flexible so that whenever a heavy obstacle is encountered the resulting impact with the blade 16 will cause the cutting portion 62 to be deflected as shown in phantom on the right side of FIG. 4 within the chamber 114 and slot 60. This will result in only the smooth circular periphery 106 of the disc 18 engaging such obstacle until the machine is either moved or shut-off.
The blade 16 will be supplied by the operator mounting a loaded hub 54 upon the cover member 56 and pulling a strip thereof through the opening 120, the chamber 114 and exiting the slot 60. This is done with the indexing means out of engagement with the openings 102 of the hub 54. Thereafter the conical projection 98 of the indexing means 84 will be snapped into one of the openings 102. Subsequently, the operator can insert the disc 18 upon the drive member 28 and secure the assembly by connecting the washer 76 and nut 78 to the end 74 of the member 28.
In operation, the cutting blade 16 rotates in the cutting circle 27 and is suitably twisted to create a "fan or vortex effect" so as to draw the blades of the grass into a vertical position for better cutting and removal thereof. Whenever a heavy obstacle is impacted by the cutting portion 62 of the blade 16 it will cause the cutting portion 62 to be deflected into the slot 60 and chamber 114. Otherwise during operation of the machine 10 the cutting portion 62 of the blade 16 will cut the grass along the cutting plane 29. Upon the cutting portion 62 becoming worn or frayed a new supply will be withdrawn from the storage portion 64 of the blade 16 and the old portion will be cut away. This process will be repeated until a fresh hub 54 having a new supply of the flexible blade 16 is required.
It will be understood that various changes in the details, materials, arrangements of parts and operating conditions which have been herein described and illustrated in order to explain the nature of the invention may be made by those skilled in the art within the principles and scope of the invention. | A machine for cutting grass and the like having a flexible strip-like cutting member supported by a disc within a housing. The strip-like member is mounted vertically and the housing has a slope such that the strip-like member is rotated to have a horizontal leading cutting edge extending beyond the housing and an inclined trailing edge which creates a vortex effect within the housing when the strip is driven by a motor to cause grass to assume a more vertical position for cutting thereof. If the cutting edge of the strip strikes an obstacle, it will be deflected into a recess in the housing rather than propelling the obstacle which might have resulted if the blade were rigid. A bottom cover plate is removably secured to the housing to permit the disc carrying the cutting member to store the same therein. Indexing of the cutting member permits measured amounts thereof to be fed from storage. | 0 |
BACKGROUND
The background of the invention will be discussed in two parts.
FIELD OF THE INVENTION
The invention relates generally to a child carrying device, and particularly to a single piece carrier worn by an adult that is generally contoured to the body of an adult for transporting the child in a natural manner upon the hip or abdomen of an adult person.
DESCRIPTION OF THE RELATED ART
Child carriers which permit a user to transport a child either on one's back or hip are well known. These carriers typically comprise a framework fabricated from pieces of aluminum tubing or PVC piping that includes a seat in which a child is placed. The seat is typically secured to the user by shoulder and waist straps. However, even though current art child carriers often are adjustable, by means of the shoulder and waist straps, to provide a more comfortable carrying position for different sized users, both the aluminum tubing and PVC piping frames are inadequate in providing sufficient comfort to prevent premature fatigue of the adult user. These frameworks also provide inadequate comfort for the child.
One such prior art child carrier is disclosed in U.S. Pat. No. 6,535,342 issued to Sundara, et al. on 10 Jun. 2003. Sundara et al. discloses a child carrier worn on the back of an adult, the carrier including a rigid frame having front and rear sections, the front section adjacent to the user's back and comprised of a pair of rigid columnar members. A restraint system includes shoulder, waist and crotch straps.
Another prior art child carrier is disclosed in U.S. Pat. No. 5,441,186 issued to Halligan on 15 Aug. 1995. Halligan discloses a child carrier comprising a basic framework fabricated from piping and a seat with removable seat back, both of a canvass material. The carrier is worn on the adult's hip and includes supporting shoulder and waist straps.
A further prior art child carrier is disclosed in U.S. Pat. No. 4,901,898 issued to Colombo, et al. on 20 Feb. 1990. Colombo et al. discloses a back-less child carrier attached to a waist belt whereby the weight of the child is distributed only about the wearer's waist and hip region. The back-less seat has a portion contoured to the hip region of the user and a portion contoured to receive and support the legs and buttocks of the child.
These patents are illustrative of the various approaches made to satisfy the existing need for improved child carriers; however, the related art concepts remain limited in this regard.
The present invention satisfies the existing need for improved child carriers by providing a unitary carrier seat contoured both to properly fit against the user's hip and abdomen and for the child to comfortably sit in an inward-facing position. The seat is contoured for comfortably positioning and supporting the child as well as contoured for the child's legs to comfortably straddle the user. An abruptly raised back portion is provided to limit any tendency of the child to slide backward on the seat. The raised back thus provides increased safety as well as a psychological feeling of safety for the child. A downward extending portion is provided for increased support and stability. The carrier has slits for attachment of adjustable shoulder and waist straps, the shoulder straps providing for distribution of the child's weight over the adults torso, thus relieving the user from uncomfortable “cutting” waist pressure of a belt-only child carrier. The straps further provide means for mounting storage pouches for such cleaning and nurturing items as may be needed when transporting a child.
It is thus an aspect of the present invention to provide a new and improved child carrier that provides comfortable and safe support for a child.
It is another aspect of the present invention to provide a new and improved child carrier that includes means for storage of child cleaning and nurturing items.
It is a further aspect of the present invention to provide a new and improved child carrier that may be mounted on the hip or stomach of an adult user and provides waist and shoulder strapping support for comfort and weight distribution of the weight of the child.
It is also an aspect of the invention to provide an improved unitary child carrier having contours configured and positioned for both user and child comfort.
It is yet another aspect of the present invention to provide an improved single piece generally child carrier having a seating platform contoured for comfortable placement of the child's buttocks and legs, an abruptly raised back for child physical and psychological security, and a downwardly extending portion providing child support and carrier position stability during use.
Other aspects, features and advantages of the invention will become apparent from a reading of the specification, when taken in conjunction with the drawings, in which like reference numerals refer to like elements in the several views.
SUMMARY
There is provided a child carrier having a child seating portion contoured for child comfort and safety, and a carrier portion contoured for stable placement of the child carrier against the user's body. The seat is designed for inward-facing of the child with the child's legs generally straddled around the user's torso and the child seating portion extending outward and upward from the user's body. The contoured carrier portion extends downward from the child seating portion to thereby provide a support brace for increased support, comfort and stability. The child carrier has slits appropriately positioned for attachment of adjustable shoulder and waist straps.
DRAWINGS
FIG. 1 illustrates the invention as worn by the user showing attachment of the shoulder and waist straps, along with accessory pouches.
FIG. 2 illustrates attachment of the waist and shoulder straps to the invention of FIG. 1 ;
FIG. 3 is a perspective view of the child carrier of FIG. 1 showing the seating portion, raised back, adult body contoured portion, and contoured left side of the seating portion;
FIG. 4 is a perspective view of the child carrier of FIG. 1 showing the bottom of the seating portion, back of the adult body contoured portion, and contoured right side of the seating portion; and
FIG. 5 is a right side view of the child carrier of FIG. 1 .
DESCRIPTION
Referring to the drawings in general there is illustrated and disclosed a unique unitary child carrier adapted to be worn on the hip or abdomen of the user and which is secured to the user's body by belt strapping about the user's waist and weight distribution strapping about a shoulder of the user. The child carrier is constructed to have sufficient strength to support the expected child weight. It can be molded of plastic, or the like, or by any other adequate process such as vacuum formed, stamped or lay up. The carrier includes contoured seating surfaces providing child and user comfort and safety, as well as a depending contoured surface providing stable positioning on the body of the user. The child carrier may be constructed of generally rigid plastic, pliable plastic, resin, rubber or other suitable material. It may be unitary and generally rigid or constructed of several parts and pliable to more aptly conform to the contour of the user. Accordingly, FIG. 1 illustrates the invention as may be worn by an adult user. The child carrier of the invention, generally designated 10 , is shown designed for inward-facing of the child with the child's legs generally straddled around the user's hip or upper leg. Although shown positioned on the user's left hip, it is understood that it can be worn on the user's right hip or in front on the user's abdomen as well.
The structure of the carrier 10 is shown in greater detail in FIGS. 2-5 where it may be seen to include a child seating portion 11 , an upturned back stop portion 11 a , buttress portion 12 , and left and right side portions 11 b and 11 c . The child seating portion 11 is laterally convexly contoured, extending backwardly and upwardly in a concave manner from buttress portion 12 and terminating in an upturned portion 11 a , the seating portion 11 thus sized and configured to minimize any tendency of the child to slide backwardly on the seating portion 11 . Thus, the seat 11 combination of lateral convexity, rearward concavity terminating in slightly upturned portion 11 a serve to position the child forwardly on the seat 11 and against the user, and therefore provide additional security for the child as well as aiding in child perceived security. This unique combination of lateral convexity and rearward concavity of seat 11 is best illustrated by FIGS. 3 and 5 .
Seating portion 11 further includes downwardly depending and contoured left and right side portions 11 b and 11 c , respectively, these side portions 11 b , 11 c designed and contoured for comfortably accepting the inward-facing child's thighs for straddling the adult user. Thus, the convex design of the seating portion 11 downward to the thigh contoured side portions 11 b and 11 c cooperate to limit the child's side-to-side movement by the natural downward position of the buttocks and thigh, thus adding comfort to the child and increasing control by the adult user. Likewise, the inward slope of the seating portion 11 forces the child to slide downward into the adult, thus limiting the child from pushing away and increasing the tendency for the child to straddle the user. Further, the thigh contoured side portions 11 b and 11 c allows the child's legs to rest in a natural position thus to decrease restriction of blood flow that would cause discomfort to the legs and thigh.
Elongated buttress portion 12 is depends downwardly from the seating portion 11 and is concavely contoured to abuttingly fit comfortably against the user's body, the elongation and contour in combination providing a stable “hugging” condition of the carrier 10 onto the body of the user. Buttress portion 12 thus sustains and distributes the weight of the child thereby providing additional comfort to the adult user by relieving stress about the waist and on the shoulder of the user. Outwardly curved portion 12 a may be included for added user comfort.
Child carrier 10 is secured to the user's body by flexible waist belt 13 which is fastened about the user's waist, and a weight distribution flexible shoulder harness 14 fastened which is about a shoulder of the user. Waist belt 13 and shoulder harness 14 are of customary planar belt-like configuration of a suitable material such as nylon strap and include auxiliary pouch means 15 and 16 , respectively. It is to be understood that pouches 15 and 16 are exemplary and other variously designed and positioned pouches may be included and/or substituted. For instance, a pouch 21 may be mounted to the underside of seating portion 11 or to the outside of depending carrier portion 12 , as indicated in FIG. 2 . Auxiliary pouches are useful for carrying child care products as well as user beverages or the like.
Both waist belt 13 and shoulder harness 14 are adjustable in length in the customary manner by means of adjustment buckles 17 , and padding such as padding 19 , may be included at selected weight bearing locations. Waist belt 13 and shoulder harness 14 have quick releasable fastener means 18 that include female portion 18 a and corresponding male portion 18 b ; it understood that other quick release fastening means that permit safe and easy mounting and dismounting of the child are acceptable. With the carrier 10 comfortably strapped to the body of the user as illustrated and described, the user has both hands free so that it is relatively easy to mount and dismount the child as may be desired.
From the foregoing, it may be appreciated that carrier 10 may be mounted to a user by first positioning shoulder harness 14 , including pouch means 16 , about a shoulder of the user and then connecting the corresponding fastener 18 . The waist belt 13 , including pouch means 15 is then placed around the waist of the user and likewise fastened with the corresponding fastener 18 . The carrier 10 and pouch means 15 , 16 are then adjusted as desired.
As best seen in FIGS. 2-4 , the carrier 10 has two arcuate slots 30 positioned in seating portion 11 proximate the arcuate intersection of seating portion 11 and depending buttress portion 12 for receiving planar shoulder harness 14 therethrough, and two rectangular slots 31 positioned in the upper area of buttress portion 12 for receiving waist belt 13 therethrough. The two slots 30 are coplanar and slightly separated for the harness 14 strap to enter through one slot and exit through the other such that the harness 14 lies flat on the inner side of buttress portion 12 as indicated in FIG. 4 . The two slots 31 are positioned in contoured buttress portion 12 diverging slightly downwardly at a slight acute angle to the vertical, one proximate the intersection of buttress section 12 and contoured side portion 11 b , and one proximate the intersection of buttress portion 12 and contoured side portion 11 c , the waist belt 13 fed through one slot and out through the other with the waist belt 13 lying flat on the inner side of buttress portion 12 as indicated in FIG. 4 .
In accordance with the above, there has been shown and described an improved child carrier. While the invention has been shown and described directed to an exemplary embodiment thereof, it is obvious that various modifications and changes may be made to the exemplary embodiment without departing from the inventive concepts contained herein. | A child carrier to be worn by a user for supporting and transporting a child including a child seating portion, a buttress support portion depending downwardly from the front end of the seating portion for abutting the body of the user supporting the child, and first and second sides downwardly depending from the seating portion to connect and brace the seating portion and the buttress support portion. The seating portion is configured for receiving a child in the user facing position, is laterally contoured generally convexly, and extends backwardly and upwardly in a generally concave manner from said buttress support portion. The carrier has slits appropriately positioned for attachment of adjustable shoulder and waist straps. | 0 |
BACKGROUND OF THE INVENTION
The invention relates to a hoisting hook assembly comprising a block with a hoisting element which consists of a shaft with attaching parts for the load ropes, which shaft is capable of rotation about a vertical axis and is supported in the block. Such an object is known in several variations and is used for hoisting large and medium large objects.
Very heavy and large-sized loads such as drilling platforms or their parts have as a rule a rectangular form. It is then usual to work with four load ropes, which ropes are fastened near the four angular points. Sometimes eight load ropes with attaching parts are used on the two long sides. Each rope ends in a loop or sling, and in the case of four ropes being used, around each of the four hooks of the hoisting element one of the slings is tied.
It is evident that the distribution of the load over the four load ropes depends entirely on the correct lengths of the four ropes. If the four taut ropes do not meet in one point, the load will, theoretically, be carried by two diagonally opposite load ropes. The elastic elongation of the ropes provides a very limited adaptation, but the latter is unreliable and, moreover, cannot be truly verified. Therefore, it is possible that that two load ropes might substantially carry the whole load. The strength and hence also the thickness of the load ropes should therefore be chosen carefully, which in the case of the very heavy loads referred to above leads to great difficulties.
SUMMARY OF THE INVENTION
The invention refers to a hoisting hook assembly aiming at obtaining a good and reliable distribution of the load with four or more load ropes.
A further object of the invention relates to the possibility of checking visually the degree of inequality of the individual rope loads in a simple way. According to the invention the shaft of the hoisting element is provided with at least two anchor-like devices capable of swinging about a central axis lying in a plane which is perpendicular to the shaft, the free ends of the anchor-like devices forming attaching parts. These features permit an additional degree of freedom, enabling the load distribution aimed at to be realized, in consequence of which it will as a rule suffice to reduce the dimensions of the load ropes to 1.2 times the nominal load calculated instead of twice, as is the case with the four-arm hoisting hook.
The invention enables more than two anchor-like devices (for instance three) to be pivotally connected to the shaft of the hoisting element in the case of hoisting a triangular or hexagonal object. Since most loads are formed by rectangular objects, the hoisting hook assembly according to the invention is preferably so constructed that the shaft of the hoisting element is provided with a central carrying element to which two swinging anchor-like devices are connected by way of mutually parallel hinge pins.
The invention further refers to a method for hoisting a load with the help of more than three load ropes, using a hoisting hook assembly indicated above. According to this method when picking up the load, one checks the angular position of the shafts of the anchor-like devices with respect to the direction of the corresponding load ropes, and one does not proceed to hoisting before the included angles are approximately equal. Consequently, this affords a visual check, which can further be facilitated if in the hoisting hook assembly according to the invention a bar is fixed at the bottom of each swinging anchor-like device in line with its axis.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side view, showing an embodiment with two swinging anchor-like devices, each with two hooks that can receive a loop or sling;
FIG. 2 is partially a view and partially the cross-section of the hoisting element in FIG. 1 according to the line II--II in that figure;
FIG. 3 is a view, similar to that of FIG. 1, of an embodiment comprising swinging anchor-like devices which receive the middle part of a continuous load rope;
FIG. 4 is partially a view and partially the cross-section of the hoisting element in FIG. 3 according to the line III-IV in that figure;
FIGS. 5 and 6 represent diagrammatically the top view and the side view of the arrangement of the load ropes and the forces involved;
FIG. 7 shows on an enlarged scale the middle part of FIG. 5, a possible small deviation from the ideal situation being represented exaggeratedly;
FIG. 8 is a variant of the hoisting element from FIG. 3, enabling hoisting processes with eight ropes by using four continuous ropes.
DETAILED DESCRIPTION
As shown in FIGS. 1 and 3, the hoisting hook assembly consists of a block 1 provided with a hoisting element 2 made up of a shaft 3 and attaching parts 4, for the load ropes 5. Shaft 3 is in the usual manner rotatable round a vertical axis supported in block 1. Further, the shaft is capable of turning slightly around a horizontal axis owing to the shaft being mounted in hinged piece 6 provided with two lateral pins 7. Block 1 is furthermore provided with two rope pulleys 8 and 9 accommodating the hoisting cable 10. Thus far the hoisting hook assembly largely corresponds to the prior art situation.
Whereas in a well-known hoisting hook assembly the attaching parts 4 for the ropes 5 are permanently fixed to shaft 3 of the hoisting element 2 and form one whole with it, the shaft of the hoisting element according to the invention is provided with at least two anchor-like devices 11 that are capable of swinging around a center line lying in a plane perpendicular to shaft 3. The free ends of these devices form the attaching parts 4 for the load ropes 5. To this end, shaft 3 of the hoisting element 2 is provided with a central carrying element 12 to which the two swinging devices 11 are connected by means of two interparallel hinged shafts 13.
In the embodiment according to FIGS. 1 and 2 each anchor-like device 11 consists of a shaft 14 having two hooks 15 for the sling 16 of a load rope 5. Each device 11 is rotatable round the centre line of its shaft 14. To this end, the shaft 14 of each device 11 is fixed to a head 18 by means of screw thread 17, the head 18 being hinged to hoisting element 2. Between the shaft 14 and the head 18 means of limiting to less than 90° the rotation of each shaft round its center line are present. Such means may, for instance, consist of a lateral pin-shaped projection 26 of the shaft 14, which projection may operate together with two stops 27 on the head 18.
There are a few remarkable points of difference between the hoisting hook assembly according to FIGS. 1 and 2 on the one hand and the embodiment according to FIGS. 3 and 4 on the other. One instance is that in the latter embodiment each attaching part 4 of a swinging anchor-like device 11 is designed as a doubly curved sliding saddle 19 in which a continuous load rope can slide. Another point of difference of the embodiment according to the FIGS. 3 and 4 with respect to the embodiment according to the FIGS. 1 and 2 is that in the latter design the shaft 3 of the hoisting element 2 is provided at its upper end, with screw thread in the usual manner, and onto this a nut 20 is screwed which rests on a rolling bearing 21. In the embodiment according to FIGS. 3 and 4 on the other hand, the central carrying element 12 is no longer whole with the shaft 3, but is an individual element provided with a hole with internal screw thread. The shaft 3 of the hoisting element 2 is designed as a bolt whose screw thread works together with the thread inside the carrying element. The head 22 of the bolt rests on the rolling bearing 21. This separation of the shaft 3 with respect to the central carrying element 12 enables the shaft to be designed as a bolt, which makes possible the manufacture from a high-alloy forged steel. This enables the diameter of the shaft 3 to be made smaller, which may produce a reduction of weight. As a consequence of this smaller thickness of the shaft 3 a smaller rolling bearing 21 can be applied, which brings about a saving of cost.
For hoisting with eight load ropes the embodiment according to the FIG. 8 is used. In it, each anchor-like device is provided with two hinged sliding saddles 19, the hinge pins 23 crossing the hinge shafts 13 perpendicularly. In each saddle 19 a continuous load rope is used. Each of the four "double" load ropes 5 then acts as attached individual ropes. The continuous rope 5 is capable of sliding through the saddle 19 as soon as the ratio of the forces in both parts of the rope exceeds the familiar ratio , where μ represents the friction coefficient and α the bearing arc length in radials. In actual practice this value will lie between 1.4 and 1.6. Consequently a large difference between the rope forces will automatically equalize in a great measure.
It is observed that the various types of swinging anchor-like devices 11 maybe screwed into the heads 18 so that the anchor like devices may be combined as desired. Thus a swinging anchor-like device with hooks may be used (FIG. 2) in combination with a swinging device, with sliding saddle (FIG. 4). Further it may be remarked that with reference to the system of forces to be discussed later with the help of FIGS. 5-7, the hinge pins 23 from the embodiment according to FIG. 8 are to be considered equivalent to the part of each sling 16 of FIG. 2, resting on the acting surface of the hook 15.
The operation of the hoisting hook assembly according to the invention is represented idealized in the FIGS. 5 and 6. In these Figures it is assumed that the center lines of two ropes attached to one anchor-like device intersect in the axis of the shaft of the device. In FIG. 5 the right hand ropes are exactly equal in length the left-hand ones differing a little in length. The hoisting hook assembly now rotates about its vertical axis until the resultant of the load-rope forces passes through the axis of the central carrying element 12. The ratio of the rope forces is now visible from the direction of the shaft 14 with respect to the load ropes 5. This is evident from the parallelogram of forces in FIG. 5. If there is a sliding saddle 19 instead of a double hook 15, then the continuous rope 5 will continue to slide until the ratio of forces equals e.sup.μα .
FIG. 7 represents the situation of the middle part of FIG. 5 on an enlarged scale, and shows in an exaggerated manner the direction of the forces when the center lines of the ropes 5 meet outside the axis of the shaft 14. The resultant of the rope forces then exerts a relatively small bending moment on the shaft of the anchor-like device and the hinge shafts 13. In addition, the shafts 14 will rotate about their axes until the center lines of the ropes attached to an anchor-like device lie in one plane. Finally, the line of intersection of the two rope planes passes through the point of intersection of the center lines of the two shafts 14. From a comparison between FIGS. 5 and 7 it appears that the actual situation (represented in FIG. 7 exaggeratedly) of the distribution of forces can be somewhat more unfavorable than the idealized situation of FIG. 5. It is noticed that in the situation of FIG. 5 the rotatability of the shafts 14 of the swinging anchor-like devices 11 with respect to the heads 18 is not necessary. Consequently, in cases in which the center lines of the ropes meet in the center lines of the shafts 14, this rotatability can be dispensed with.
In the FIGS. 5 and 6 the load is represented as a rectangular element 24. Further, in FIG. 7 a rod 25 is also shown which is also shown in FIG. 2. The center line of this rod is a continuation of the center line of the shaft 14 of the swinging anchor-like device 11. The presence of this rod facilitates the visual verification of the measure of inequality of the individual rope loads. It should be remembered that in the case of hoisting very heavy loads such as drilling platforms and the like, cranes with very large dimensions are concerned, in consequence of which the hoisting hook assembly may be situated at a considerable distance of the verifying person. The presence of the rod 25 now makes it possible, in the case of an unfavorable ratio of the rope forces, to take action in good time and perform the required correction of the length of the rope.
An important practical advantage of the invention is that the hoisting hook assembly can be mounted in a simple way in any existing conventional hoisting block. This makes possible a replacement of the conventional hoisting hook by the hoisting hook assembly according to the invention with comparatively little loss of time at little cost. | A hoisting hook for at least four ropes comprising a block, a shaft rotatably supported in said block and a plurality of anchor-like devices rotatably supported in said shaft, so that sufficient degrees of freedom are created for the ropes to divide the hoisting load equally over the ropes. | 1 |
FIELD OF THE INVENTION
This invention relates to a container having four side walls and a base, for collecting and keeping newspapers, periodicals and the like. The base is separated from the underside of the container itself, and between this underside and the base, there is provided at least one receiving compartment having an opening leading to the outside of the container.
BACKGROUND OF THE INVENTION
A container for this purpose is known from DE-GM (German Utility Model) 84 12 523. In that container, newspapers, periodicals, and the like are deposited in the container and are collected there until the container is full. Below the bottom of the container there are two receiving compartments, each of which contain a supply of string. The string is appropriately placed over the top sides of the container and, when the container is filled, all that has to be done is to knot the string, after which the newspapers and periodicals can be removed from the container in the form of tied-up stacks.
In this known state of the art, the two receiving compartments for the balls of string are formed of special slide-in parts that are fixed to the container. These special slide-in parts, which consist of wood or metal, make the container generally uneconomical to produce.
In contrast, the purpose of the invention at hand is to improve the known container to the effect that, coupled with simple storage and transportation conditions for the container, both the structure and ease of handling will be improved and the stability of the container will be increased.
SUMMARY OF THE INVENTION
To solve this problem, the invention provides a container made essentially of a folding cardboard box. The container, on its underside, has a second base spaced from the base provided. The second base is an intermediate base that can be removed form its required position. The base of the container carries a supporting structure which, in turn, carries the intermediate base spaced from the base of the container and which, at the same time, defines at least one receiving compartment between the base and the intermediate base.
A container according to the invention, in contrast to the known prior art, includes a double base, consisting of a lower base and an upper intermediate base, which simultaneously, in connection with the supporting structure carrying the upper intermediate base, defines a receiving compartment for balls of twine. The container according to the invention can be made, stored and transported as a folding cardboard box, at little cost, and is particularly stable and steady in terms of its shape because of the double base.
To insert a new ball of twine, it is not necessary to lift the container, as in the prior art. Instead, it is only necessary to take out the removable intermediate base and, after insertion of the new balls of twine, to replace the intermediate base in its proper position.
The supporting structure could be made as a part of the folding lower base of the container. Preferably, however, it is made of a separate part that is placed loosely upon the lower base of the container. In particular, the supporting structure is made as a cross-shaped cardboard support. The two bars of the cross-shaped support, which may be secured together, run inside the container diagonally from corner area to corner area; in other words, they are received in the container in such a manner that they cannot be moved around while, at the same time, they increase the stability of the container.
The intermediate base could likewise be a part of the folding cardboard box, especially when, according to another preferred feature of the invention, the container as a whole is made with double walls. Alternatively, the additional base may be a one-piece component of the folding cardboard box. The intermediate base can be inserted loosely into the container. Preferably, the intermediate base has at least one grasping opening or handle that facilitates lifting and removing the intermediate base.
Other advantageous features of the invention result from the claims as well as from the subsequent description in which several practical examples of the invention are described in greater detail, based on the drawings. The drawings illustrate the invention, partly in a semi-schematic or schematic fashion.
BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 is a perspective view of a container according to the invention;
FIG. 2 is a perspective view similar to FIG. 1, illustrating the path of the twine;
FIG. 3 is an exploded view showing assembly of the container of FIG. 1.
FIG. 4 is a top plan view of the individual parts of the container in the unfolded state; and
FIG. 5 is a cross-section through an alternative version of a container according to the invention.
DETAILED DESCRIPTION OF THE INVENTION
The box-like container according to FIGS. 1 to 4 has four side walls 10, 20, 30, and 40, a lower base 50 that closes off the underside of the container, a cross-shaped support 60 that rests on base 50, and an intermediate base 70 resting upon cross-shaped support 60. The dimension of intermediate base 70 essentially correspond to the inside dimensions of the container. Cross-shaped support 60 has two bars 62, 64, each of which runs diagonally between two side edges of the container and, in terms of its length, roughly corresponds to the diagonal. Cross-shaped support 60 subdivides the compartment between base 50 and intermediate base 70 into four receiving compartments, two of which, that is, receiving compartments 80, 82, serve as receiving compartments for a supply of twine, for example, balls of twine 84, 86. In the area of receiving compartment 80 or 82, side wall 10 or 20 includes a central aperture 88 or 90 through which twine 85 or 87 from ball of twine 84 or 86 is guided to the outside. The further guidance of the twine can be seen particularly from FIG. 2. On the upper edges 11, 21, 31, 41 of side walls 10, 20, 30, or 40, there are made, in each case, in the middle, wedge-shape cuts 12, 22, 32, or 42, that clamp the corresponding lengths of twine or ends of twine firmly. Twine 85 is guided from opening 88 upward to notch or cut 12, from there, downward to intermediate base 70, across intermediate base 70 centrally with respect to side wall 30, along side wall 30 upward to cut 32, and finally it is clamped firmly in place with its end across cut 32 with the end protruding outside. Correspondingly, string 87 is guided from opening 90 upward to cut 22, from there again downward to intermediate base 70, across intermediate base 70 to the opposite side wall 40, along side wall 40 upward to cut 42. The end of the string is clamped firmly so that it will protrude on the outside, as can be seen in FIG. 2.
When newspapers are placed in the container according to FIG. 2 and when the container is filled up, then it is only necessary to pull the strings or string ends to the corresponding length, whereby the balls of string will become unwound automatically. The strings are then cut off on one side and, finally, the strings are knotted together. The newspaper stack, thus made and tied up, can then be removed from the container. The string ends, protruding out of openings 88, 90, are then grasped and the strings are again moved into the position illustrated in FIG. 2 so that the container can be filled up again.
On upper edge 21, near side wall 10, there is another cut 92, to the base of which a knife 94 is attached. It is thus possible to sever strings 85, 87, without requiring a separate cutting tool, such as scissors or knife. If a new supply of string is to be inserted into receiving compartments 80, 82, then it is only necessary to grasp the intermediate base 70 by opening 72 therein and to lift it or to remove it from the container. After insertion of the new balls of twine and after the ends of the twine have been threaded through openings 88 or 90, intermediate base 70 is very simply again placed upon cross-shaped support 60.
The container as a whole is made of cardboard. Side walls 10, 20, 30, and 40, as well as base 50, are made in a one-piece blank for a folding cardboard box, as illustrated particularly in FIG. 4. The two bars 62, 64 of cross-shaped support 60 are separate parts, as is intermediate base 70.
The container may be made overall, in a double-wall fashion for its side walls and base. The folding cardboard blank for this purpose has a central fold 100. As illustrated in FIG. 4, side wall parts that are positioned adjacent each other are, in each case, formed above and below fold 100. When the container is assembled, fold 100 represents upper edge 11, 21, 31, 41. Side wall 10 is made up of side wall parts 10a, 10b, side wall 20 is made up of side wall parts 20a, 20b, side wall 30 is made up of wide wall parts 30a, 30b, and side wall 40 is made up of side wall parts 40a, 40b. Side wall parts 10a, 20a, 30a, and 40a form the parts which will be the outside when in the assembled state, while side wall parts 10b, 20b, 30b, and 40b form the particular parts that are located inside the container. Side wall part 10a is fastened to side wall part 40a by means of clips 14 that are formed on its vertical edge and inserted into corresponding slits between flap 44 of side wall part 40a and side wall part 40a.
Other folds run along the preformed fold lines 102, 104, that run parallel to fold 100 spaced at the height of the side walls. Base parts 50a, 50b, 50c and 50d, which adjoin side wall parts 10a, 20a, 30a and 40a, beyond fold line 104, form the underlying part of double-wall base 50. Base parts 50e, 50f, 50g and 50h, adjoining side wall parts 10b, 20b, 30b and 40b, beyond fold line 102, form the interior base of double-wall base 50. It should be noted that side wall parts 10b, 20b, 30b, and 40b, which lie inside the container, like the inside-lying parts 50e, 50f, 50g, and 50h, are spaced from each other, as can be seen in FIG. 4.
It can furthermore be seen in FIG. 4 that bars 62, 64 of cross-shaped support 60, likewise, in each case, consist of folding parts which, to increase stability, in each case are folded at a central fold line 62a, 64a. The two bars 62, 64 can be secured together centrally by securing slits 62b, 64b that run perpendicularly to fold lines 62a, 64a.
Containers according to the invention can be offered with varying dimensions in keeping with the particular customary newspaper or periodical sizes. The version according to FIG. 5 represents a development of the practical example according to FIGS. 1-4 to the extent that, in this case, the intermediate base is not made as a separate part but rather is incorporated in the one piece folding cardboard blank and is fashioned by two (possibly overlapping) intermediate base parts 74, 76 which are connected with side wall parts 20b, 40b by corresponding fold lines. These side wall parts 20b, 40b, are made correspondingly shorter when compared to the example shown in FIG. 4.
Likewise, in an alternative development of the invention, the support structure carrying the intermediate body could be incorporated in the one piece folding cardboard blank and, for example, could be connected with several of the interior base parts 10b, 20b, 30b, or 40b. | A container for collecting and storing newspapers and periodicals comprises a lower base, a cross-shaped support that rests on the lower base, and an intermediate base that rests on the cross-shaped support. Between the lower base, the cross-shaped support and the intermediate base, two receiving compartments for receiving balls of twine are defined. The container as a whole is made as a folding cardboard box and is distinguished by great stability as well as simple handling. | 1 |
RELATED APPLICATIONS
This application is a divisional of U.S. patent application Ser. No. 08/874,154 filed Jun. 13, 1997, now U.S. Pat. No. 5,827,330 which is a continuation-in-part of U.S. patent application Ser. No. 08/568,057 filed Dec. 6, 1995, now U.S. Pat. No. 5,686,084.
Attention is directed to concurrently filed U.S. patent application Ser. No. 08/568,056, now U.S. Pat. No. 5,702,712, filed Dec. 6, 1995, which describes melanin reaction products having properties similar to those of the products of this invention, but which are prepared from different starting materials.
BACKGROUND OF THE INVENTION
This invention relates to water soluble reaction products prepared by the oxidative polymerization of quaternized 5,6-dihydroxyindole-2-carboxylic acid amides or esters, to compositions containing such products, to methods of coloring hair or treating skin utilizing the compositions and to kits containing the compositions. More specifically, the invention relates to reaction products characterized by a quaternary nitrogen substituent and to intermediates useful for the preparation of the reaction products.
The reaction products of this invention are mixtures of many compounds formed by the oxidative polymerization of the aforementioned amide or ester derivatives of 5,6-dihydroxyindole-2-carboxylic acid (DHICA). The oxidative polymerization of DHICA and certain of its selected derivatives is described in commonly owned U.S. Pat. No. 5,346,509, the disclosure of which is incorporated herein by reference. The particular DHICA derivatives which are oxidatively polymerized to form the products of this invention are neither described nor suggested in the '509 patent.
To facilitate understanding of this invention, the following system will be employed in its description:
A: The oxidative polymerization products should be understood to be the reaction products of the invention. In addition to the term “reaction products of the invention”, they are sometimes referred to as hair colorants, hair dyes or skin treatment products and, often, melanin like products of the invention.
B: The quaternized products formed by reaction of DHICA with selected quaternary compounds to be described more fully hereinafter are referred to as “intermediates” or as “intermediates of the invention”.
C: Compositions of the invention may take several forms depending on their intended use. If the products of the invention are to be directly added to the hair, they will be formed on the hair by oxidative polymerization of intermediates of the invention in an aqueous media. If they are to be employed for skin care they may be aqueous, non-aqueous or they may be mixtures of polar or non-polar organic solvents and may be either free flowing or viscous.
Notwithstanding their melanin-like properties, the reaction products of this invention are not true melanin derivatives. The reaction products of the present invention are mixtures of many compounds and thus cannot be precisely defined by a chemical formula. Accordingly, they will be defined herein by their method of preparation. It is believed that the mixture of the compounds comprising the reaction products of this invention includes some dimers, trimers and tetramers of the intermediates. However, most species are oligomers and many are probably true polymers. Surprisingly, they have substantially similar hair coloring and other properties compared to the melanin derivates described in U.S. Ser. No. 568,056 (CP1141).
Naturally-occurring melanin is the pigment that gives hair its color. A general discussion of the properties and chemistry of melanins may be found in Prota, G., “Progress In The Chemistry of Melanins And Related Metabolites”, Mcd. Res. Reviews, 8:525-56 (1988) and Moncrieff, R. W., Manufacturing Chemist, 8, 330-34 (August 1950). The gradual reduction of melanin formation with age causes hair to become gray.
Naturally-occurring melanin pigment itself is unacceptable for use in a hair dye composition because it is easily removed by rinsing or rubbing and leaves the hair feeling rough. One present method for coloring gray hair involves the use of naturally-occurring melanin precursors such as DMI that when combined with an oxidant, form useful melanin like pigments. See, for example, U.S. Pat. No. 3,194,734 (Seemuller et al.), U.S. Pat. No. 4,808,190 (Grollier et al.), and U.S. Pat. No. 4,888,027 (Grollier et al.). See also U.S. Pat. No. 5,346,509 (Schultz et al.) which describes the conversion of DHICA to melanin like pigments.
The primary disadvantage is that the hair colors initially produced with melanin precursor dyes are undesirable achromatic colors (cold grays and blacks). Hair dyed with these colorants must undergo a second treatment step with an oxidant such as hydrogen peroxide to achieve natural chromatic colors (warm yellows, reds, and browns). See, for example, U.S. Pat. No. 3,194,734 (Seemuller et al.). In addition, melanin precursors are expensive and, because they are highly reactive, are difficult to work with. The use of melanin precursors also can result in undesirable scalp and skin staining.
Furthermore, because the pigments are formed from the melanin precursors in the hair shaft the hair colors produced using the melanin precursors are permanent. The hair color must grow out to return to its original color. Often, consumers prefer to use a temporary hair color that will wash out after one or two shampoos.
The compositions described in PCT patent application Ser. No. US93/11174 filed Nov. 17, 1993 are usefull as temporary hair colorants. These compositions contain melanin derivatives prepared by forming a complex between a water soluble anionic melanin with selected quaternary compounds, suitably alkyltrimonium halides, alkylalkonium halides or dialkyldimonium halides such as cetrimonium halide or stearalkonium halides. These complexes impart a temporary coloring to human hair when deposited thereon in aqueous compositions and thereafter dried. Although such compositions are acceptable to many consumers, they may not be acceptable to others because they wash off the hair too readily. Only rarely do they survive a single shampoo. In fact, normally they require a “leave on” treatment since they may be readily removed with even a water rinse.
The art has sought hair coloring compositions providing colors that are not as difficult to use as the melanin precursors or as permanent dyes, but are more permanent than the colors provided by the above described temporary hair colorants, i.e. dyes which will survive 4 to 6 shampoos or can be mixed with additional dyes in a shampoo base in order to freshen temporary hair colors. The hair colorants utilized in the compositions of this invention have these desirable properties. In that respect they are similar to the products of the above identified U.S. Ser. No. 568,056 (CP-1141), but are prepared differently.
The compositions of this invention produce in a single treatment step semi-permanent natural-looking hair color that resist fading in sunlight, resist rub off and resist bleeding in contact with water. The compositions are inexpensive and simple to work with. It has surprisingly been found that aqueous compositions containing the reaction products of this invention will, when applied to hair, impart a semi-permanent color to the hair which will survive more than three shampoos without substantial loss of color characteristics. A particular advantage of the reaction products of this invention is that they can be combined with other hair colorants in a shampoo base to freshen the existing hair color whereby the hair color is renewed and retained for an appreciably further period of time. Another is that the reaction products can be used for simultaneous coloring and conditioning of hair.
The products of this invention are also useful for skin care. They may be used alone or, preferably, in conventional skin care compositions. When so employed, they function both as skin colorants to impart a tanned appearance to the treated skin and as sun screen agents to protect the skin from harmfull infrared rays.
With both skin and hair, the products exhibit the other attributes of natural melanin, i.e., they are antioxidants and free radical scavengers and minimize hair damage caused by oxidants and free radicals often present in the hair after atmospheric exposure.
U.S. Pat. No. 5,006,331 (Gaskin) discloses the use of melanin compositions containing triethanolamine and ferric chloride. The resultant mixture of melanin, triethanolamine and ferric chloride is said to be useful for skin protections, for wound healing and for strengthening hair. An alternate composition contains trypsin in an alkaline medium. Melanin is present in the skin protectant compositions of Gaskin in an amount of from about 0.001 to about 0.09%, along with from about 0.0001% to about 0.27% ferric chloride, both being on a weight basis based on total weight. The skin protectant composition further contains up to about 5% by weight triethanolamine. While not providing a range of concentration for the amount of melanin hydrolysate for the hair protectant compositions according to her invention, Gaskin states at column 6, line 30 that it is present therein in an amount of only about 0.0015% by weight of the total composition. However, this level of Gaskin's melanin hydrolysate is wholly insufficient to impart a color to hair. Moreover, neither of Gaskin's methods provide a melanin material of a cationic character.
PCT Application WO 91/17738 discloses the use of soluble melanin derivatives in a process for producing lightly colored melanins that are aesthetically suitable for use in cosmetic compositions.
WO 94/25532 describes melanin linked to a lipid to form a lipomelanin and its use in a sunscreen product.
It is an object of this invention to provide an aqueous composition for semi-permanently coloring hair using water soluble melanin like products of the invention.
It is also an object of this invention to provide compositions that will produce a semi-permanent natural-looking hair color that resists fading in sunlight, will not rub off, and will not bleed when in contact with water.
It is further an object of this invention to provide inexpensive compositions for semi-permanently coloring hair using water soluble melanin like products of the invention.
It is also an object of this invention to provide compositions that are simple to work with for semi-permanently coloring hair using water soluble melanin like products of the invention.
It is also an object of this invention to provide a one-step process for semi-permanently coloring hair.
It is a further object of this invention to provide a composition for simultaneously coloring and conditioning hair.
It is a still further object of this invention to provide compositions which when used with appropriate shampoos are usefull for freshening hair colors.
It is a still further object of this invention to provide novel melanin like products of the invention and compositions thereof for skin care.
It is a still further object of this invention to provide novel intermediates useful for the production of melanin like products of the invention.
SUMMARY OF THE INVENTION
The presently preferred products of the invention are quaternary substituted esters or amides which may be obtained by oxidative polymerization of a novel intermediate of the invention represented by the formula:
wherein:
R is hydrogen or a substituent that is chemically non reactive in the polymerization reaction, typically an alkyl containing from about 1 to about 6 carbon atoms, and preferably methyl or ethyl.
R 1 , R 2 and R 3 are groups that in combination one with the other and with R 4 quaternize the nitrogen to which they and R 4 are bonded,
R 4 is a linking group as defined below, and
X is an anion.
The intermediates of this invention as will be recognized from the above formula are quaternary substituted esters or amides obtained by reacting DHICA or its N-substituted derivatives with a quaternary ammonium salt, N⊕R 4 (YH)R 1 R 2 R 3 X − . R 1 ,R 2 ,R 3 and R 4 (YH) maybe any chemical group suitable to quaternize the nitrogen to which they are bonded, and that does not prevent ester or amide formation when the DHICA species and the quaternary salt are reacted. The quaternized melanin amide or ester precursor compounds (I) of the invention may be prepared from any of a wide variety of quaternary compounds that react with DHICA or its N-substituted derivatives. The quaternized melanins of this invention are obtained by oxidative polymerization of the intermediate compound (I), and have cations that interact with hair and become attached to the hair by a cation/anion attraction of the cation for the anionic hair. It is this electronic attraction of the cation of the quaternary compound for the anionic charge of the hair which renders the hair colorants of this invention semipermanent rather than temporary as are the hair dyes of the above cited PCT patent application Ser. No. US93/11174 filed Nov. 17, 1993.
Suitably, R 4 may be an unsubstituted or substituted alkylene group having from 1 to 20 carbons, preferably a straight chain unsubstituted alkylene group having 6 to 15 carbons, and R 1 , R 2 or R 3 may be an unsubstituted or substituted alkyl group having from 1 to 22 carbons, preferably one of R 1 , R 2 or R 3 having from 12 to 16 carbons and two of R 1 , R 2 or R 3 having from 1 to 6 carbons. The alkylene and alkyl groups are preferably straight chained. Suitable substituent groups present in R 4 , R 1 , R 2 and R 3 may be hydroxy; mono- or polyhydroxyalkyl and alkyloxy, mono- or polyhydroxyalkyloxy, the alkyl group having from 1 to 6 carbons, preferably 1 to 4 carbons, especially 1 to 2 carbons, with typically up to about 3 hydroxy groups; amino and alkylamino with up to about 6 carbons, preferably 1 to 3 carbons; halo; cyano, and nitro. R 4 , R 1 , R 2 and R 3 may also be an unsubstituted or substituted alkylamino group having 1 to 6 carbons, preferably 1 to 3 carbons; an alkylene or dialkylene substituted alicyclic or aryl group, especially phenyl but also cyclohexenyl and naphthyl, the alkylene group(s) having from 1 to 6 carbons, or a heterocyclic such as pyrolle, morpholinyl or piperidinyl. Any of the aryl, alicyclic or heterocyclic groups may be further substituted as set forth above with respect to the alkyl (or alkylene) group. The selection of a substituent group is limited only with regard to whether ester or amide formation would be compromised, and whether the reaction product of the DHICA species and quaternary is sufficiently soluble to permit formulation in an aqueous-based hair dye product. The substituent groups should not impart instability to the molecule in view of steric hindrance or otherwise.
As previously mentioned the quaternary reactant has at least one amino or hydroxy group YH associated with R 4 that is available to form an amide or ester compound in accordance with this invention. However, R 4 may have two or more reactive hydroxy or amino groups associated with it. Similarly, any of R 1 , R 2 and R 3 may also have one or more additional hydroxy or amino groups. When multiple reaction sites are available for amide or ester formation, the reaction will take place at one of them. The other substituents present on R 4 , R 1 , R 2 and R 3 of the quaternary reactant are chemically compatible with respect to ester or amide formation but may be further reacted to produce desired colors.
The above identified products are especially preferred when they are prepared from quaternary compounds containing an unsubstituted amninoalkylene or hydroxyalkylene group together with at least one other long chain alkyl group attached to the positively charged nitrogen. The most preferred products of the invention are those which contain at least one long chain alkyl group and at least one short chain alkyl group containing from about 1 to 6 carbon atoms, suitably methyl or ethyl. Although the invention contemplates products in which all of the R 4 groups are long chain, these are not preferred because they are difficult to prepare due, principally, to steric hindrance.
Suitable quaternary materials that may be used in the practice of this invention are set forth, generally, in the CTFA Cosmetic Ingredient Handbook (1st Ed., 1988) at pages 40-42 (quaternary ammonium compounds). The entire disclosure of this citation is incorporated herein by reference. Suitability of specific compounds may be determined by one of ordinary skill in the hair dye art by simple experimentation. They are compounds which will react with DHICA to produce intermediates which can be oxidatively polymerized to form the positively charged products of the invention having at least one counterion which is an anionic moiety, e.g., a halide or methosulfate. Using the nomenclature of the CTFA Handbook, which is widely used and accepted by chemists in the cosmetic art, illustrative cationic materials are hydroxy or amino substituted alkyl trimonium halides, alkylalkonium halides and the dialkyldimonium halides, wherein the allyl groups have about 1 to about 22 carbons and the halide is Cl or Br. Useful quaternium compounds include for example, the quaternium series of compounds such as Quaternium 16, 22, 30, 36, 46, 78, 79, 80 and 82. Other suitable quaternary reactants will be readily apparent to the skilled artisan after the benefit of this disclosure.
It will be apparent from the foregoing that the quaternary compounds used to produce intermediates may contain a variety of functional groups both in the main chain or attached thereto.
The anion in the intermediates of this invention may be any of those normally associated with quaternary compounds. Typically they are halides, preferably chlorides or bromides.
DETAILED DESCRIPTION OF THE INVENTION
The intermediates of the invention may be formed by any of the usual methods of forming amides or esters.
For example, to form amides, DHICA may be reacted with an aminoalkyl substituted quaternary compound in an aqueous buffer at a pH of about 7 at ambient temperature in the presence of a carbodumide such as 1-ethyl-1,3-(3-dimethylaminopropyl)carbodiimide.
Esters may be prepared for example, by reacting equimolar quantities of the reactants in an aqueous buffer at pH 7.
The intermediates of this invention may be oxidatively polymerized by a number of procedures known to those skilled in the art. The melanin like products of the invention may be produced by treatment of the selected intermediate with an oxidizing agent such as, for example, hydrogen peroxide, potassium ferricyanide, potassium permanganate or ammonium persulfate. These procedures are well known and are described for example in U.S. Pat. Nos. 5,173,083; 5,346,509; 5,273,550 and 4,804,385, the entire disclosures of which are incorporated herein by reference.
The amount of quaternized melanin like hair colorant required in the aqueous hair dye compositions of this invention whether the hair colorant is preformed or formed on the hair will vary according to factors such as the carrier used, the initial hair color of the user prior to dyeing, the desired end hair color and other factors well known to those skilled in the art. A tinctorially effective amount of hair colorant should be used. In general, the amount required is at least about 0.1%, typically from about 0.1% up to its solubility limit in the composition, but generally up to about 5.0%, and preferably from about 0.2% to about 3.0%, all concentrations being on a weight basis based on the total weight of the composition.
Skin compositions employing the products of this invention are generally less concentrated than those used as hair colorants. Typically, they will contain from about 0.01% to 10%, preferably 0.05% to 1% of at least one product of the invention dissolved, emulsified or suspended in a pharmaceutically acceptable skin vehicle which may be aqueous or non-aqueous and may comprise water, inert oils, emollients, surfactants, buffers or other additives such as those illustrated in the examples.
Although the pH of the aqueous compositions of this invention may not be so low or high as to damage skin or hair, the compositions are useful at a wide range of pH values. The optimal pH for a particular composition may vary with the hair colorant employed. In general, however, the pH of the composition will be about 3 to about 10, preferably 5 to 10.
In addition to the selected hair colorant or mixture of hair colorants of the invention, it may be desirable to include cosmetically acceptable carriers in the hair colorant compositions of this invention. Acceptable carriers vary from simple solutions or dispersions with aqueous or alcoholic solvents to complex mixtures that contain thickening or other agents. The carriers that may be used in accordance with this invention must be compatible with the selected dye.
It may also be desirable to include in the compositions of this invention adjuvants or additives that are commonly found in such compositions, in amounts effective to provide their intended function. Such adjuvants or additives include, for example, solvents, solubilizing agents, surfactants, thickening agents, alkalizing agents, chelating agents, preservatives and fragrances.
The solvents that may be used include organic solvents or solvent systems that are compatible with the other components. A number of organic solvents are known in the art that are useful for such purposes. These organic solvents include alcohols, particularly alkyl alcohols of 1-6 carbons, especially ethanol and propanol; and glycols of up to about 10 carbons, especially diethyleneglycol; monobutyl ether; carbitols and benzyl alcohol.
The thickening agents that may be used include, polyvinylpyrrolidone, gum arabic, cellulose derivatives such as methylcellulose or hydroxyethylcellulose, and inorganic thickeners such as bentonite. The solubilizing agents that may be employed include for example, ethoxylated fatty alcohols. The preservatives that may be used include: methyl and propyl paraben, 2-phenoxyethanol, DMDMH and Kathon CG.
A special advantage of the hair colorants of this invention is that certain of them can be employed to both color and condition the hair at the same time. It is known that when long chain alkyl substituents containing certain quaternary ammonium salts are deposited on human hair, they improve combability, i.e., the relative ease with which hair can be combed, by imparting a certain lubricity to the hair as well as by providing an antistatic effect. Both of these effects combine to make the hair easier to manage so that the desired appearance of the hair can be more readily achieved. Compositions having these properties are called “hair conditioners”. See, for example, A. C. Lunn and R. E. Evans, The Electrostatic Properties of Human Hair, J. Soc. Cosmet, Chem., 28, 549 (1977).
Products of this invention formed by oxidative polymerization of intermediates having one substituted or unsubstituted alkyl groups containing from about 12 to about 16 carbon atoms are preferred for both colorant and conditioning properties. Quaternary reactants usefull for such concurrent activity include, for example, several of the Quaternium compounds mentioned above.
In another preferred aspect of the invention, the water soluble products of the invention are incorporated into a shampoo base which also contains auxiliary hair colorants to effect simultaneous coloring and cleaning of the hair. This feature of the invention is especially useful to freshen the color of previously dyed hair.
Shampoos are well known to those skilled in the art and need not be described with any particularity. In general, they are aqueous solutions containing from about 1% to about 50% by weight of a surfactant which may be cationic, anionic, non-ionic or amphoteric. Suitable surfactants include for example, behenealkonium chloride, dodecyldimonium chloride, sodium lauryl sulfate, sodium laureth sulfate, cocamidopropyl betaine and cocamidopropyl sultaine. Other useful surfactants may be identified by resort to McCutcheon's Emulsifiers and Detergents (North Amer. Edition 1987) which is incorporated herein by reference. In the compositions of this invention, the amount of surfactant is about the same as employed in conventional shampoos.
It will be appreciated that none of the various additives described above can be employed in the hair colorant compositions of the invention if they insolubilize the hair colorants of the invention at any concentration.
A further aspect of the present invention is the optional incorporation of one or more known hair color modifiers in the hair colorant compositions of the invention. These include for example, direct dyes, primary intermediates and couplers.
The concentration of hair color modifier is normally less than about 10 mg/ml, and preferably is present in the reaction medium at from about 0.01 to about 5 mg/ml, most preferably from about 0.05 to about 2 mg/ml. The amount of these components should not be so great as to cause precipitation of the hair colorants of the invention.
A wide variety of direct dyes, primary intermediates and couplers are known to the skilled artisan and can be employed in this invention.
The presently preferred primary intermediates and couplers with which they will react include:
Primary Intermediates:
p-phenylenediamine
p-aminophenol
o-aminophenol
N,N-bis(2-hydroxyethyl)-p-phenylenediamine
2,5-diaminopyridine
p-toluenediamine
Couplers:
resorcinol
m-aminophenol
α-naphthol
5-amino-o-cresol
2-methylresorcinol
4,6-di(hydroxyethoxy)-m-phenylenediamine
m-phenylenediamine
Suitable direct dyes include, for example nitro dyes, azo dyes and anthraquinone dyes.
This invention also provides a process for coloring hair, which comprises applying to the hair an aqueous composition comprising a product of the invention. The compositions may be applied to the hair by conventional techniques known in the art. For example, they can be poured over the hair or applied with an applicator. The amount of time for which the dye composition must be in contact with the hair is not critical. It may vary from about 2 minutes to about one hour, but is usually from about 5 minutes to about 30 minutes.
While the presently preferred method of utilizing the products of the invention as hair colorants is to apply the preformed oxidatively polymerized melanin like products directly to the hair in aqueous compositions, it is also possible to achieve hair coloration or to treat skin by mixing an oxidant with an intermediate of the invention just prior to application or during application so that a product of the invention is formed on the hair or skin.
The invention also includes kits containing a composition of this invention. A kit may comprise one container which contains a composition including all of the various components described above. Alternatively, there may be two or more containers each containing separate components which are mixed on the hair or just prior to application to the hair or skin, or after application thereto.
The hair coloring effects achieved with the products of this invention may be evaluated utilizing the standard Hunter Tristimulus values. In the Hunter method, the parameters a and b may be positive or negative and define the chromatic condition of the hair. Thus, the more positive the a value, the greater the redness of the hair, while a negative a value indicates greenness. Similarly, positive b values indicate yellowness, while negative b values indicate blueness. The L parameter is a measure of color intensity, and has a value of 0 for absolute black to 100 for absolute white.
The following non-limiting examples are given by way of illustration only. In the examples, the formation of a cationic, positively charged pigment was shown by electrophoretic measurements in 0.05M sodium borate buffer, pH 9 at 250 Volts.
EXAMPLES
Abbreviations used: MES buffer is morpholinoethylsulphonate. EDC is 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. DHICA is 5,6-dihydroxyindole-2-carboxylic acid.
Example 1
Reaction Product of Oxidatively Polymerized DHICA-Quaternium 22
A solution of DHICA (200 mg) in nitrogen flushed 0.1 M MES buffer, pH 7 (40 ml) is treated with 1.74 ml of Quaternium 22, maintaining pH at about 7. A few mg of sodium dithionite are added, followed by 150 mg of EDC under nitrogen. After 1 h, an additional 150 mg portion of EDC is added, and the resultant mixture is left at room temperature under stirring and under nitrogen until almost all the DHICA has been consumed (about 20 h). The crude mixture is then treated with potassium ferricyanide (1 g) in 0.1 M phosphate buffer (20 ml) at room temperature with continuing stirring. After 1.5 h, the solution is dialyzed against water over at least 10 h. The pigment which separates is collected by centrifugation and washed with water.
Example 2
A 1% solution of the product of Example 1 in pH 10 buffer was prepared and applied to bleached hair for 15 minutes. Afterwards, the hair was rinsed with water and dried.
Hunter
L
a
b
before treatment
66.4
1.4
18.7
after treatment
42.7
3.2
14.5
A noticeable color and conditioning effect is imparted to the hair. The hair was shampooed, rinsed and dried. A significant amount of hair colorant remained on the hair.
Hunter
L
a
b
shampooed hair
51.7
2.0
16.2
Example 3
A skin care composition is prepared by thoroughly mixing the following components:
Product of Example 1
0.1%
Methyl cellulose
0.5%
Glycerin
2.0%
Ethanol
11.0%
Water
85.5%
Fragrance
Q.S. 100%
When applied to the skin, the composition imparted a darker color.
Example 4
DHICA (1.5 g) is dissolved in DMF (4 ml) and is treated with a solution of 2-aminoethyltrimethyl ammonium chloride (4 g) in water (3 ml) followed by EDC (5.45 g) solubilized in a mixture of water (2 ml) and DMF (4.5 ml). After about 1 h, 3 g of EDC is added and the mixture is stirred for additional 45 min. Sodium periodate (2 g) in water (12 ml) is then added and the mixture is allowed to stand under stirring for 20 min. Oxidation is eventually stopped with a small amount of sodium bisulfite and the resulting pigment is dialyzed against water and lyophilized.
Example 5
A sunscreen composition is prepared by thoroughly mixing the following components:
Product of Example 1
0.1
Ethyl dihydroxypropyl PABA
2.0
Propylene Glycol
20.0
Oleth-20
4.7
Laneth-16
4.7
water
68.5
When applied to the skin the composition afforded protection against sun rays. | Water soluble, cationic compounds useful as hair colorants or for the treatment of skin which are esters or amides formed by reaction of 5,6-dihydroxyindole-2-carboxylic acid or its N-substituted derivatives and a quaternary salt containing a reactive amino or hydroxyl group, and polymers from such compounds obtained by oxidative polymerization. | 0 |
BACKGROUND OF INVENTION
[0001] This invention is directed to flat horizontal support members, namely, tables, and more specifically to a simple system by which a conventional table or table base may be quickly and easily provided with an alternative or interchangeable table top surface appearance or configuration, whether ornamental, or functional, such as display advertising, game boards, instructional work stations, and the like.
[0002] The prior art is exemplified by U.S. Pat. No. 4,841,878 granted Jun. 27, 1989 to Elliot Kreigsman, which is directed to a see-through table top and the prior art described therein, namely U.S. Pat. No. 1,850,420 granted on Mar. 22, 1932 to S. J. Schuldt for “Game Table”; U.S. Pat. No. 3,001,843 granted on Sep. 26, 1961 to S. D. Davis for “Convertible Table”; and U.S. Pat. No. 3,227,105 granted on Jan. 4, 1966 to R. Reisdorff et al for “Table”; all of whose tables are relatively complex in construction; U.S. Pat. No. 3,212,952 granted on Oct. 19, 1965 to J. Turner for “Decorative Table” which provides an aesthetically pleasing table top; but one which must remain as set up by the manufacturer; and U.S. Pat. No. 2,833,609 granted on May 6, 1958 to C. J. Lawless for “Table Construction With Reversible Top” which is not only relatively complex in construction but only provides either one of only two table top configurations.
OBJECTS AND SUMMARY OF INVENTION
[0003] Broadly stated, the interchangeable table top according to the present invention, in one form, comprises a frame of a size and shape to fit over the top surface and around the edges of the top of an existing, conventional table. In one embodiment, an upwardly facing horizontal shoulder is spaced downwardly from the top edge of the frame and extends inwardly around the inner perimeter of the frame. A backer board is supported on the shoulder and permanently secured to the frame. The backer board in turn supports a replaceable and interchangeable table top insert member, which serves as a substrate for whatever ornamental, promotional (e.g., for advertising), entertainment, or other imaging as may be desired, with the image being applied to a top surface of the insert member. The frame defines a recess of given dimensions, and the insert has equal dimensions so that it fits rather precisely into the accommodating recess. The replaceable imaged table top insert member is releasably secured, using suitable releasable attaching means, to the backing board. Favorably, the top surface of the replaceable table top insert member is substantially flush with the edge of the frame. The backer board is provided with means for releasing the insert member from the backer board when it is desired to change the insert member out for a different insert member. In a preferred embodiment this can be constituted by one or more finger holes in the backer board. This feature facilitates separation of the releasably secured imaged table top. In an alternative form of the invention, the backer board may replace the conventional table top and be permanently secured to the table base. In such case, the backer board would be of suitable thickness to serve as a table top, and the pedestal base or other leg members would be fastened directly to the bottom surface of the backer board.
[0004] The above and other features and embodiments of this invention will become apparent from the following description of a preferred embodiment, which is to be read in conjunction with the accompanying Drawing figures in which corresponding parts are identified by the same reference numerals.
BRIEF DESCRIPTION OF THE DRAWINGS
[0005] [0005]FIG. 1 is a perspective elevational view of a conventional pedestal table having an interchangeable table top according to the present invention, shown with parts broken away to reveal hidden structures;
[0006] [0006]FIG. 2 is a top plan view of the table top frame, shown with parts broken away to reveal hidden structure;
[0007] [0007]FIG. 3 is a bottom plan view of the replaceable table top; and
[0008] [0008]FIG. 4 is a fragmentary vertical isometric section showing details of construction;
[0009] [0009]FIG. 5 is a perspective view of a table top insert on which is imprinted a holiday theme design.
[0010] [0010]FIG. 6 is a perspective view of a table top insert on which is imprinted a game board design, i.e., a chess board.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0011] Referring now to the Drawing, and initially to FIG. 1, a conventional pedestal table 10 has a normal or standard permanently attached table top 11 , and an interchangeable table top 12 according to the present invention is installed on top of the aforementioned permanent table top 11 . The interchangeable table top 12 includes a rigid frame 14 of a size and shape to fit over the top surface and around the edges of the standard top 11 of a conventional table with a slide fit. The invention is adapted to use with virtually any table. Although the invention is illustrated with respect to a rectangular table top, which is the most common shape, the table top arrangement may take the form of a table of any other standard geometric shape, i.e., circular, oval, elliptical, hexagonal, or the like. Non-standard shapes, e.g., horseshoe, semi-circular, or other shapes, are also possible. Although shown as a pedestal base table, this invention is equally applicable to multi-legged tables.
[0012] With further reference to FIGS. 2, 3, and 4 , the frame 14 is shown to include an upwardly facing horizontal lip or shoulder 15 spaced downwardly from the top edge 16 of the frame and extending inwardly around the inner perimeter of the frame. In the assembled structure, the surface of lip or shoulder 15 lies in a common plane with the top surface of table top 11 . The bottommost portion 17 of frame 14 below lip or shoulder 15 functions as a drop or skirt surrounding and engaging the side edges of the normal table top 11 with a slide fit. Frame 14 may be fabricated from wood, or it may be made from a molded, extruded or machined synthetic resinous plastic material, or a lightweight metal, such as aluminum or the like.
[0013] A rigid backer board 18 is supported within frame 14 supported on lips or shoulders 15 and permanently secured to the frame by means of nails or screws and/or adhesive. The dimensions of the backer board are the dimensions of table top 11 plus the widths of two lips or shoulders 15 . The frame 14 and the backer board together define a recess 26 , which in this embodiment is rectangular in shape. The recess 26 is of specific dimensions and is intended to receive an insert which will be described shortly. In the illustrated embodiment of the invention, the backer board 18 is intended to rest on the normal table top 11 . Here, the lower part of the frame extends below the backer board 18 and defines a lower recess 27 that fits the permanent table top 11 . In an alternative form, backer board 18 replaces conventional table top 11 and is permanently secured directly to a table base. In both forms it supports an interchangeable rigid planar table top insert 19 whose exposed upper surface 20 functions as a substrate for any of innumerable types of images, and whose bottom surface 22 overlies the back board, space therefrom by releasable fastening means. The “image” may be as simple as a plain over all color, or it might be an erasable surface on which indicia may be drawn and then removed, and the like. The table top insert 19 has the same dimensions as the recess 26 , and fits snugly within the recess 26 , surrounded by the frame 14 .
[0014] There are first and second releasable attaching means disposed on the bottom of the insert 19 and on the upper surface of the backer board 18 , and these may be complementary strips or patches of an interlocking hook and loop type filamentary fastening material, such as that sold under the trademarks Velcro® and Scotchmate®. The releasable fastening means may be in the form of strips 22 and 23 attached, respectively to the top surface of backing board 18 and the bottom of surface 21 of table top 19 . The strips 22 and 23 are desirably attached adjacent all peripheral edges of the backing board and table top insert, desirably supplemented by centrally located filamentary fastening means, such as the X-patterns 24 and 25 on the respective backing board and the table top insert. In this embodiment, the releasable fastening means must be arranged on the respective surfaces in complementary mirror image patterns so that they engage when the parts are pressed together. The patterns may have two-way or four-way symmetry so that the user does not have to be concerned with the orientation of the insert relative to the frame and backer-board portion. At least one finger hole, and preferably a plurality of finger holes 27 are provided through backer board 18 to facilitate separation of the releasable fasteners when it is desired to replace or exchange an imaged table top insert 19 . Favorably, the table tops can each be provided with a set of several interchangeable inserts 19 . The variety of possible inserts is inexhaustible.
[0015] Instead of using complementary patterns of filamentary fastening strips on both the top side of backer board 18 and bottom side 21 of table top 19 , the strips on one of the surfaces may be eliminated and replaced by a napped textile fabric covering the surface. When the top of the backing board 18 has a smooth glossy surface, suction cups may be used as the fastening means. Other releasable fastening means may be employed, such as magnetic strips or releasable mechanical fasteners.
[0016] The depth of lip or shoulder 15 is such that the combined thicknesses of the backer board 18 , joined releasable fasteners 22 - 25 and imaged table top insert 19 cause the insert top surface 20 to be substantially flush with the top edge 16 of the frame 14 , as in a high quality piece of furniture, disguising any appearance of being temporary or interchangeable. The outer top edge 16 of frame 14 is desirably rounded, as shown.
[0017] The number of different images which may be applied to the top surface 20 of the interchangeable table top insert 19 is limitless. Examples include display advertising, abstract designs, holiday theme materials designs, such as Christmas theme images (See insert 19 ′—FIG. 5), play surfaces such as checker boards (See insert 19 ″—FIG. 6), or boards for such games as Parcheesi, Poker, Monopoly, etc., ornamental and decorative simulated wood and stone surfaces, sports schedules, etc. The table top of this invention is intended to be suited for commercial usage, such as food courts, lunchrooms, cafes, etc., but may be used in any environment where tables are used, such as game rooms, class rooms, or other environments. The principle of this invention provides a simple easy way of adapting the table tops to meet varying situational needs on a time sensitive and efficient basis. For example, the tables 10 can be arranged with holiday inserts 19 ′ for a holiday party, and then quickly changed over for another event by changing out the inserts, for example using the inserts 19 ″ for a chess tournament. The inserts 19 can be imprinted with designs that carry advertisements for local merchants, with the inserts 19 being changed over when the businesses change, or when advertising or promotional campaigns so dictate.
[0018] While the invention has been described with respect to a selected preferred embodiment, it should be recognized that the invention is not limited to that embodiment, and that many modifications and variations would be apparent to persons skilled in the art without departure from the scope and spirit of this invention, as defined in the appended claims. | An interchangeable table top arrangement has a frame and backer board that can fit over a pre-existing table top or can be attached to a pedestal and used as a main table top. The frame and backer board define a recess, and an interchangeable insert fits into this recess. A hook-and-eye material (i.e., Velcro®) or other suitable releasable attachment system hold the insert in place within the frame. Finger holes in the backer board facilitate separating the attachment system to change out the insert. The inserts may have designs imprinted on them, e.g., advertising, holiday theme material, or game boards. | 0 |
CROSS-REFERENCE TO RELATED APPLICATION(S)
[0001] This application is a continuation of U.S. patent application Ser. No. 13/207,489 filed on Aug. 11, 2011, which respectively claims priority to U.S. Provisional Patent Application No. 61/401,310 filed on Aug. 11, 2010; U.S. Provisional Patent Application No. 61/463,390 filed on Feb. 16, 2011; and China Patent Application No. 201110215584.0 filed on Jul. 29, 2011, which are incorporated herein by reference.
BACKGROUND
[0002] 1. Field of the Invention
[0003] The present invention relates to child holding accessories that may be suitable for use with play yards.
[0004] 2. Description of the Related Art
[0005] Play yards are used to contain and provide a safe environment for a child to sleep or play. Currently, most play yards are constructed to include a frame around which a fabric element is wrapped and stretched to form the boundaries of the play yard. Due to the wide spread use of play yards, efforts have been made to increase their versatility to caregivers. For example, some child holding accessories may be added to play yards, such as changing tables (also commonly called “changers”, bassinets, and child sleeping beds (also sometimes called “nappers”). While these different types of accessories may provide more versatility, it may be expensive to purchase a different accessory for each use. Moreover, it may also be cumbersome to store multiple child holding accessories, or to change the accessory for each different use.
[0006] Therefore, there is a need for an improved child holding accessory that may be more convenient in use, provide comfortable resting support and address at least the foregoing issues.
SUMMARY
[0007] The present application describes a child holding accessory that can be used in combination with a rigid support frame. The child holding accessory can be desirably installed on the rigid support frame, and integrate multiple regions adapted to receive the child in different configurations of use. Examples of construction for these holding regions can include, without limitation, a changing table and a child sleeping bed.
[0008] In one embodiment, the child holding accessory includes a reversible resting support and at least one fixture for attaching the resting support with a rigid support frame.
[0009] The reversible resting support has a first and a second bearing surface facing opposite directions, the first and second bearing surfaces respectively having different profiles, and each of the first and second regions being positionable to be upwardly facing to receive a child thereon.
[0010] Moreover, the present application also describes an infant support apparatus that includes a rigid support frame, a reversible resting support, and at least one fixture rotatably connected with the resting support. The reversible resting support has a first and a second bearing surface facing opposite directions, the first and second bearing surfaces respectively having different profiles, and each of the first and second regions being positionable to be upwardly facing to receive a child thereon. The fixture is configured to attach the resting support with the rigid support frame at an elevated position above a floor, and the resting support being rotatable relative to the fixture attached to the rigid support frame to position either of the first and second bearing surfaces upwardly facing.
[0011] At least one advantage of the structures described herein is the ability to provide a child holding accessory that can integrate two opposite regions adapted to receive the child in different configurations of use. The bearing surfaces associated with the two regions can deform differently when the child is placed thereon. Accordingly, the bearing surfaces of the two regions can be designed to provide differential firmness and bending curvature that suits the different functional uses of the two regions.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] FIG. 1 is a schematic view illustrating a play yard provided with a child holding accessory in a first configuration of use;
[0013] FIG. 2 is a schematic view illustrating the play yard of FIG. 1 with the child holding accessory in a second configuration of use;
[0014] FIG. 3 is a schematic view illustrating a first side of the child holding accessory;
[0015] FIG. 4 is a schematic view illustrating a second side of the child holding accessory opposite to the first side;
[0016] FIG. 4A is a schematic side view of the child holding accessory with the second region turned upward;
[0017] FIG. 5 is a schematic cross-sectional view illustrating the construction of a resting support in the child holding accessory;
[0018] FIG. 6 is a schematic view illustrating the construction of a support board that can be assembled in the resting support;
[0019] FIG. 7 is a partially enlarged view illustrating portion A of FIG. 6 ;
[0020] FIG. 8 is a schematic view illustrating another embodiment of a support board that can be assembled in the resting support;
[0021] FIG. 9 is a partially enlarged view illustrating portion B of FIG. 8 ; and
[0022] FIG. 10 is a schematic view illustrating yet another embodiment of a support board that can be assembled in the resting support of the child holding accessory.
DETAILED DESCRIPTION OF THE EMBODIMENTS
[0023] The present application describes a child holding accessory that can be used in combination with a play yard. The child holding accessory can integrate multiple regions adapted to receive the child in different configurations of use. Examples of construction for these holding regions can include, without limitation, a changing table and a child sleeping bed. Each of the holding regions can be designed to deform differently when the child is placed thereon so as to provide adequate resting support.
[0024] FIGS. 1 and 2 are schematic views illustrating an embodiment of a child holding accessory 102 suitable for use with a play yard 104 , and FIGS. 3 and 4 are schematic views respectively illustrating two opposite sides of the child holding accessory 102 . Referring to FIGS. 1 and 2 , the play yard 104 can include a rigid support frame 106 over which is held an enclosure 108 that defines an inner space 110 opened upward. In one embodiment, the enclosure 108 can be made of a flexible cloth material that is stretched around the support frame 106 to define multiple sidewalls surrounding the inner space 110 . The child holding accessory 102 can be detachably mounted at an upper side of the enclosure 108 above the inner space 110 . The child holding accessory 102 is thereby adapted to receive a child at an elevated position on the play yard 104 for facilitating the care of the child.
[0025] The child holding accessory 102 can be constructed as an adjustable module that includes a resting support 114 having multiple regions adapted to receive the child. Examples of these regions can include, without limitation, a first region R1 constructed as a changing table, and a second region R2 constructed as a child sleeping bed on a side opposite to the side of the first region R1. The child holding accessory 102 can be adjustable to turn the second region R2 downward and the first region R1 upward to be used as a changing table (as shown in FIG. 1 ), or to reversely turn the first region R1 downward and the second region R2 upward to be used as a child sleeping bed (as shown in
[0026] FIG. 2 ). This adjustment of the child holding accessory 102 can be permitted by using one or more adjustable fixtures 130 A, 130 B to attach the resting support 114 with the play yard 104 .
[0027] In one embodiment, the resting support 114 can include a surrounding frame 132 formed from multiple tubular segments connected together, and a bearing platform 134 affixed with the surrounding frame 132 . The adjustable fixtures 130 A and 130 B may be mounted with two opposite sides of the surrounding frame 132 , and are adapted to fasten the resting support 114 with two opposite handrails of the play yard 104 . In one embodiment, at least one of the two adjustable fixtures, for example adjustable fixture 130 A, can include a rotary mechanism that is operable to permit relative rotation of the resting support 114 . While the adjustable fixture 130 A is attached with the support frame 106 , the resting support 114 thus can be rotated relative to the play yard 104 to turn either of the first region R1 and the second region R2 upward. The other fixture 130 B can have an adjustable catch 136 that can bear on the associated handrail of the play yard 104 .
[0028] FIG. 3 shows the first region R1 of the child holding accessory 102 , and
[0029] FIG. 4 shows the second region R2 of the child holding accessory 102 . As shown in FIGS. 3 and 4 , the first region R1 used as a changing table can have a relatively flat bearing surface BS 1 . The first bearing surface BS 1 thus can provide a stable support to allow a parent to conveniently change the child's diaper. The second region R2 used as sleeping bed can have a second bearing surface BS 2 that has a raised head portion 138 that is higher than other regions of the second bearing surface BS 1 . According to one embodiment, the head portion 138 can be formed by a piece of fabric that has one edge sewed at a higher position, or that is securely held with the fixture 130 A via a strap. The child can be placed on the second bearing surface BS 2 with the head resting at a higher level on the head portion 138 so as to provide a more comfortable sleeping position.
[0030] The left and right sides of the surrounding frame 132 can also include side frame segments 132 A that have a curved shape. When the first region R1 is turned upward, the side frame segments 132 A can respectively have curved shapes that project/arch upward to gather and tighten a fabric material between the surrounding frame 132 and the first bearing surface BS 1 . Moreover, the side frame segments 132 A can increase the height of the left and right side edges of the changing table, which can prevent the child from accidentally falling down and provide safer use. When the second region R2 is turned upward, the curved shapes of the side frame segments 132 A are projecting/arching downward to facilitate downward bending of the second bearing surface BS 2 and provide comfortable sleeping support.
[0031] In conjunction with FIGS. 3 and 4 , FIG. 4A is a schematic side view illustrating the child holding accessory 102 with the second region R2 turned upward. The surrounding frame 132 can also include a head-side frame segment 132 B and a foot-side frame segment 132 C that are transversally connected between the side frame segments and respectively mounted with the fixtures 130 A and 130 B. The fixtures 130 A and 130 B can respectively define pivot points P1 and P2 through which a rotation axis a can pass. The head-side frame segment 132 B and the foot-side frame segment 132 C can be arranged at different distances H1 and H2 from the rotation axis α, such that the head-side frame segment 132 B can be higher than the foot-side frame segment 132 C.
[0032] According to one embodiment, the surrounding frame 132 can be entirely located at a same side of the rotation axis α, and the distance H1 between the head-side frame segment 132 B and the rotation axis α can be smaller than the distance H2 between the foot-side frame segment 132 C and the rotation axis α. When the first bearing surface BS 1 is turned upward, the surrounding frame 132 can be located above the rotation axis α and the foot-side frame segment 132 C can be at a position higher than the head-side frame segment 132 B to facilitate diaper changing. In contrast, when the second bearing surface BS 2 is turned upward to be used as a sleeping bed, the surrounding frame 132 can be located below the rotation axis α and the foot-side frame segment 132 C can be at a position lower than the head-side frame segment 132 B to provide comfortable sleeping support.
[0033] FIG. 5 is a schematic cross-sectional view illustrating the resting support 114 . The bearing platform 134 can include a flexible cushion element 140 and a support board 142 . The cushion element 140 can be assembled to enclose the support board 142 , and include a first layer 144 on the side of the first region R1, and a second layer 146 on the side of the second region R2. The first and second layers 144 and 146 can be joined together by sewing, bonding or other suitable techniques. In one embodiment, the first layer 144 used for the changing table can include a fabric that is water-proof and easy to wipe-off, like polyvinyl chloride (PVC)-based or ethylene vinyl acetate (EVA)-based polymer materials. The second layer 146 used for the sleeping bed can include soft and comfortable fabric, like cotton cloth or flannelette. It will be understood that the first and second layers 144 and 146 are not limited to the aforementioned examples, and other flexible/soft materials may be included, such as webbing materials, foamed polymer pad and the like.
[0034] The support board 142 can be placed between the first and second layers 144 and 146 , and have a first side 142 A and an opposite second side 142 B. Two opposite ends of the support board 142 can be connected with the surrounding frame 132 via connecting elements 148 , such as straps, cords, and the like. The support board 142 can provide a support sufficiently rigid for sustaining the weight of the child received in either of the first and second region R1 and R2. In the meantime, the support board 142 can also be designed to deform differently depending on whether the child is supported on the bearing surface BS 1 or BS 2 . For example, the support board 142 can bend freely when the child is placed on the bearing surface BS 2 to conform to the child's body and provide comfortable sleeping. On the other hand, when the child is placed on the bearing surface BS 1 , bending of the support board 142 is reduced or prevented to provide a flat and stable surface for better accessibility while changing the child's diaper. Exemplary embodiments of the support board 142 are described hereafter with reference to FIGS. 6 through 10 .
[0035] FIG. 6 is a schematic view illustrating one embodiment of a support board 202 that can be assembled in the bearing platform 134 and provide the aforementioned deformation capabilities, and FIG. 7 is a partially enlarged view illustrating portion A of FIG. 6 . The support board 202 can be integrally formed in a single piece from a plastics material. The support board 202 can have a first side 202 A and an opposite second side 202 B, and include an array of hollow cells 210 that are joined together. Each cell 210 can include a plurality of sidewalls 210 A, 210 B and 210 C that delimit an inner cavity 212 of the cell 210 . Adjacent cells 210 can have their respective sidewalls 210 B connected each other on the second side 202 B, such that that the cells 210 can be joined together at the second side 202 B of the support board 202 . On the other hand, the first side 202 A of the support board 202 can include a plurality of slits 216 that are respectively delimited between the sidewalls 210 C of each pair of adjacent cells 210 , and separate from one another the sidewalls 210 A of the cells 210 on the first side 202 A of the support board 202 .
[0036] The slits 216 can partly disconnect the cells 210 from one another so as to allow relative deflecting movements between the cells 210 . When the support board 202 is assembled with the cushion element 140 , the first side 202 A can lie adjacent to the first layer 144 (i.e., corresponding to the first region R1), and the second side 202 B adjacent to the second layer 146 (i.e., corresponding to the second region R2).
[0037] Referring to FIGS. 3 through 6 , when the child is supported on the second region R2, the weight of the child is applied from the second side 202 B of the support board 202 . This pressure can cause the cells 210 to pivot about their respective joining portions. As a result, the cells 210 can deflect relative to one another in a way that enlarges the slits 216 and splits the sidewalls 210 C of adjacent cells 210 away from each other. Accordingly, the support board 202 can freely bend in a first direction D1, which causes the bearing surface BS 2 to sink and suitably conform to the child's body for providing a comfortable resting position. Aside bending movements, the inner cavities 212 can also permit the cells 210 to deform to provide comfortable support of the child.
[0038] On the other hand, when the child is supported on the first region R1, the weight is applied from the first side 202 A of the support board 202 . This pressure can cause the sidewalls 210 C of adjacent cells 210 to contact against each other, which can substantially prevent bending of the support board 202 in a second direction D2 opposite to the first direction D1. As a result, the first bearing surface BS 1 can provide a flat and stable support for better accessibility while changing the child's diaper.
[0039] The support board 202 can therefore deform differently depending on whether the load of the child's weight is exerted from the first side 202 A or the second side 202 B of the support board 202 , which can result in different firmness of the first and second bearing surfaces BS 1 and BS 2 . The firmness of the first and second bearing surfaces BS 1 and BS 2 can be assessed by determining how each of the first and second bearing surfaces BS 1 and BS 2 bends and the depth to which it sinks upon application of a load pressure, i.e., the bend curvature and sinking depth of the support board 202 can be different depending on whether the child's weight is applied from the first side 202 A or second side 202 B For example, the second bearing surface BS 2 can bend and sink to a greater depth when the child is placed thereon, whereas the first bearing surface BS 1 can hardly sink when the child is placed thereon. Accordingly, the bearing platform 134 can provide adequate support curvatures respectively in accordance with the required use conditions, e.g., the changing table requires a flat surface for easy accessibility, and the sleeping bed requires a bent curvature for increased comfort.
[0040] FIG. 8 is a schematic view illustrating another support board 302 suitable for use with the bearing platform 134 described previously, and FIG. 9 is an enlarged view of portion B shown in FIG. 8 . The support board 302 can be similar to the support board 202 in construction, having a first side 302 A and an opposite second side 302 B, and including an array of hollow cells 310 that are joined together. Each cell 310 can include a plurality of sidewalls 310 A, 310 B, 310 C and 310 D that delimit an inner cavity 312 of the cell 310 . Adjacent cells 310 can have their respective sidewalls 310 B connected each other on the second side 302 B, such that the cells 310 can be joined together at the second side 302 B of the support board 302 . On the other hand, the first side 302 A of the support board 302 can include a plurality of slits 316 A and 316 B that respectively extend parallel to two intersecting directions X and Y. The slits 316 A can be delimited between the sidewalls 310 C of two adjacent cells 310 , and the slits 316 B can be delimited between the sidewalls 310 D of two adjacent cells 310 . As a result, the sidewalls 310 A of the cells 310 can be separated from one another, and the slits 316 A and 316 B can partly disconnect the cells 310 so as to allow relative deflecting movements between the cells 210 .
[0041] When the support board 302 is assembled with the cushion element 140 , the first side 302 A can lie adjacent to the first layer 144 (i.e., corresponding to the first region R1), and the second side 302 B adjacent to the second layer 146 (i.e., corresponding to the second region R2). Like previously described, when the child is supported on the second region R2, the weight of the child is applied from the second side 302 B of the support board 302 . This pressure can cause the cells 310 to pivot about their respective joining portions. Because the joining portions of the cells 310 extend along two directions X and Y, the support board 302 can bend in different planes of curvature. As a result, the capacity of the support board 302 to deform is increased to better fit the shape of the child's body. When the child is supported on the first region R1, the weight is applied from the first side 302 A of the support board 302 . This pressure can cause the sidewalls 310 C and 310 D of adjacent cells 310 to contact against each other, which can substantially prevent bending of the support board 302 in the second direction D2.
[0042] FIG. 10 is a schematic view illustrating the construction of another support board 402 . The support board 402 can include two board elements 404 , and a resilient joint element 408 . The board elements 404 can be made from any rigid materials, such as plastics, woods and the like. The joint element 408 can elastically deform to allow relative displacement between the board elements 404 . In one embodiment, the joint element 408 can have a flex structure similar to that of the support board 202 or 402 , having opposite first and second sides 408 A and 408 B and including a plurality of hollow cells 410 provided with inner cavities 412 . The cells 410 can be joined together on the second side 408 B of the joint element 408 , and disconnected on the first side 408 A via a plurality of slits 414 . The joint element 408 can thus freely deform when the load pressure is applied from the second side 408 B. In contrast, bending deformation of the joint element 408 can be substantially prevented when the load pressure is applied from the first side 408 A.
[0043] It is worth noting that the support board structures described herein may be advantageously used for any child holding devices in general. For example, seat modules in stroller, car seat, high chair and swing apparatuses may also use any of the support board structures illustrated above to provide increased comfort.
[0044] At least one advantage of the structures described herein is the ability to provide a child holding accessory that can integrate two opposite regions adapted to receive a child in different configurations of use. In particular, the child holding accessory can include a support board that can deform differently depending on the region where the child is placed. As a result, the bearing surfaces associated with the two regions can present different firmness to provide adequate resting of the child.
[0045] Realizations in accordance with the present invention therefore have been described only in the context of particular embodiments. These embodiments are meant to be illustrative and not limiting. Many variations, modifications, additions, and improvements are possible. Accordingly, plural instances may be provided for components described herein as a single instance. Structures and functionality presented as discrete components in the exemplary configurations may be implemented as a combined structure or component. These and other variations, modifications, additions, and improvements may fall within the scope of the invention as defined in the claims that follow. | A child holding accessory includes a reversible resting support and at least one fixture for attaching the resting support with a rigid support frame. The reversible resting support has a first and a second bearing surface facing opposite directions, the first and second bearing surfaces respectively having different profiles, and each of the first and second regions being positionable to be upwardly facing to receive a child thereon. | 0 |
BACKGROUND OF THE INVENTION
This application relates to an apparatus and method for transferring dry chemicals from a container, such as a railcar, and forming a solution or slurry of the chemical in a liquid carrier medium. The invention is particularly suitable for use with chemicals which form hydrates, in particular soda ash, and which therefore are difficult to handle using known transfer means.
Various means have been described for transferring dry materials out of containers. For example, U.S. Pat. No. 3,512,842 describes a method for unloading railcars in which a slurry is formed inside the railcar and then is pumped out. Such a process has numerous drawbacks, however, including the risk of overflowing or foaming within the car; the need for specialized railcars adapted for use in the slurrying process; the possibility of corrosive solutions being formed and damaging the railcar; problems with residual moisture causing caking in subsequent shipments; and the formation of hard, slowly dissolving lumps when liquid is added to a large quantity of solid. A similar approach is described in U.S. Pat. No. 4,189,262.
Eductors have been used and are still used to transfer dry chemicals as a slurry, solution or solid. For example, liquid driven eductors have been used to slurry dry polymers and activated carbon in the water treatment industry and to transfer fly ash in the electric power industry. Also air, steam, and liquid driven eductors have been used for transfer of solids. However, problems are known to exist with eductor-based handling systems.
For example, air driven eductors require a high power input and air flow per unit mass of solid conveyed resulting in high energy costs and higher capital cost for dust collection equipment. Steam driven eductors are used to create a vacuum for pneumatic conveying of dry solids to a solid-liquid mixing apparatus. The systems using steam driven eductors which are known to the inventors require a large amount of support equipment including a barometric leg for condensing the steam with modifications for solid-liquid mixing, and a large steam supply. Since the solid is conveyed by vacuum, the steam driven eductor system is limited by economics to installations where it can be located near, e.g. within a few hundred feet of, the container of dry chemical.
Liquid driven eductors do not require large volumes of air or steam and can be used to transfer dry chemicals from a container, such as a railcar, forming a solution or slurry of the chemical in the liquid carrier medium. Liquid driven eductors are known to be successfully used to prepare dilute solutions of polymer in water as well as to transfer insoluble materials, e.g. activated carbon, to storage as a slurry. However, the inventors are unaware of any liquid-driven eductor system used to transfer and dissolve or slurry dry hydratable solids when the motive liquid is a concentrated solution of the solid being transferred. In tests using concentrated solutions of a dry hydratable solid (i.e. soda ash) as the motive fluid to convey said solid, the throat of the eductor rapidly plugged with hydrates making frequent cleaning necessary. Also, tests using water as the motive fluid to convey a hydratable solid (e.g. soda ash) showed that plugging of the eductor occurred making cleaning necessary.
It is an object of the present invention to provide an apparatus and method for transferring solids, and particularly hydratable dry chemicals from a storage container, which avoids the plugging problems associated with known eductor systems. It is a further object of the invention to achieve this goal using a simple apparatus which is readily used in concert with conventional railcars.
SUMMARY OF THE INVENTION
According to the invention, an apparatus for the transfer of a dry chemical is formed having a sealed solvation hopper positioned between a liquid driven eductor and a fitting for connection to a storage container, e.g. a railcar. At the inlet end of the solvation hopper is a chemical inlet pipe which connects the interior to the exterior of the hopper. Surrounding the chemical inlet pipe are a plurality of nozzles for the introduction of solvation liquid into the hopper. The nozzles are disposed such that the solvation liquid washes the interior surface of the hopper to prevent plugging by hydrates (solvates) which may be formed. At the outlet end of the hopper, the hopper is connected to the suction opening of a liquid driven eductor.
In use, the exterior end of the chemical inlet pipe is connected to the dry chemical storage container. Liquid flowing through the eductor creates a suction and draws dry chemical out of the storage container and into the hopper. In the hopper, solvation liquid is supplied through the nozzles to wet the dry chemical and to wash the surfaces of the hopper, pushing the wetted material toward the outlet end of the hopper. At the outlet end of the hopper, the wetted material is sucked out into the eductor where it is combined with the flow of eductor liquid. The material leaving the eductor is recovered and sent either to storage or directly for processing.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an isometric drawing of an apparatus according to one embodiment of the invention.
FIG. 2 is an assembly drawing of the same apparatus shown without the eductor.
FIG. 3 is a piping diagram for an apparatus where the storage container is a railcar and the solution or slurry produced in the invention is sent to storage. In the example described by the piping diagram, solution of any concentration up to saturation and slurries of solid in saturated solutions of said solid may be prepared by using solution recycled from storage as the liquid for the eductor.
DETAILED DESCRIPTION OF THE INVENTION
Looking at FIG. 2, the apparatus of the invention comprises a solvation hopper formed from a wall member 9 and an inlet end member 6. The chemical inlet pipe 13 passes through the inlet end member 6 to provide a connection between the interior and the exterior of the hopper.
The portion of the dry chemical inlet pipe interior to the solvation hopper is not intentionally wetted with solvation liquid because it is difficult to prevent zones of quiescent liquid from forming on the pipe. For example, if the outer wall of said pipe is wetted, the liquid is relatively quiescent at the end of the pipe and on the inner wall where capillary action draws the liquid. Hydrates can accumulate in these quiescent zones causing plugging. The portion of the dry chemical inlet pipe interior to the solvation hopper may, however, be unintentionally wetted by spray from the hopper and eductor and for this reason is preferably coated with or constructed from a non-stick material having a low coefficient of friction such as polytetrafluoroethylene (i.e. Teflon® PTFE). The portion of the dry chemical inlet pipe exterior to the solvation hopper may be constructed of a material chosen for strength (e.g. metal) as this portion of the inlet pipe is not susceptible to plug formation, or it can be made of the same material as the interior portion. Thus, the solvation hopper formed from wall member 9 and inlet end member 6 and the exterior portion 1 of the chemical inlet pipe 13 are advantageously constructed from materials chosen for strength, e.g. metal, and the interior end 8 of the chemical inlet pipe 13 is preferably constructed from or coated with a material chosen for its low coefficient of friction, e.g. polytetrafluoroethylene.
The exterior end 1 of the chemical inlet pipe 13 has means for connecting the inlet pipe to a conduit for transporting solids to the apparatus of the invention. FIG. 2 shows the means for connecting the inlet pipe to said conduit as threaded but any type of connection, e.g. flanged, can be used.
Surrounding the interior end 8 of the chemical inlet pipe 13 at the inlet end of the hopper are a plurality of nozzles 7 comprising downspouts fitted with commercially available liquid spray nozzles, e.g. Spraying Systems Company Veejet. The nozzles 7 convert the pressure energy of the solvation liquid into kinetic energy and are disposed to direct the solvation liquid to wash the solvation hopper wall member 9. In a preferred embodiment of the invention, the nozzles 7 are oriented at an angle of 45° below the horizontal and feed the solvation liquid so that said liquid enters approximately tangential to the solvation hopper wall member 9. In this manner a swirling action is created in the solvation hopper which ensures that all surfaces of the solvation hopper wall member 9 are washed with solvation liquid. The nozzles 7 are connected to a means for supplying the solvation liquid, for example, to an annular manifold. In FIG. 2 such a manifold is formed from item 2, an annular top, item 3, an annular outer wall, item 4, an annular bottom, item 5, a solvation liquid inlet, and item 12, an annular inner wall. FIG. 1 clearly shows the location and appearance of the manifold. The outlet end 10 of the hopper is connected to the suction opening of a liquid driven eductor as shown in FIG. 1.
In a preferred embodiment, the same liquid is used as both the solvation liquid and to power the eductor. In this case, as shown in FIG. 3, a pipe connects the eductor's liquid inlet pipe to the manifold of items 2,3,4,5 and 12 of FIG. 2.
In use, the exterior end 1 of the chemical inlet pipe 13 is connected to one end of a conduit. The other end of said conduit terminates at a container of dry chemical in such a manner as to permit the dry chemical to enter the conduit. The conduit may be, for example, a flexible hose, formed from a material compatible with the chemical to be transported. Liquid is supplied through a pipe to an eductor which generates a vacuum in the hopper which draws dry chemical from a container, through the conduit, through the chemical inlet pipe 13 into the solvation hopper constructed of items 9 and 6, where it is mixed with solvation liquid from nozzles 7, and into the eductor. To obtain the most efficient utilization of the eductor, it should be located close to dry chemical storage container. In this manner, a high solid to air mass ratio, e.g. 100 can be obtained.
The solvation liquid is supplied through nozzles 7 from the annular manifold, which in the preferred embodiment of the invention receives liquid from the inlet side of the eductor. Nozzles 7 are chosen so that the volumetric flow rate of liquid entering the solvation hopper is controlled and is small compared to the suction capacity of the eductor chosen for use. FIG. 3 is a schematic diagram of the use just described.
As shown in FIG. 1, the solvation hopper may advantageously have a conical section tapering downward toward the outlet end. It may also be cylindrical, or have a curved section. Preferably, however, there will not be any ledges on the interior of the hopper which would impede movement of wetted material toward the outlet end of the hopper and which might promote plugging. Although it is particularly suited for use with hydratable materials such as soda ash or calcium chloride, the apparatus of the invention can advantageously be used to transport a wide variety of chemical materials, including nonhydratable chemicals such as sodium bicarbonate and insoluble materials such as sand.
It will be appreciated that the identity and flow rates of the solvation liquid and the eductor liquid, which can be the same of different, will be selected to optimize the transport process. Thus, the solvation liquid is preferably supplied at a rate sufficient to prevent plugging of the hopper, yet too high a rate is undesirable as this will reduce throughput of the transported chemical for any given flow rate of eductor liquid.
As part of the method of this invention empirical correlations are presented for proper sizing of the apparatus. These correlations are based on the suction capacity of the eductor chosen, expressed in actual cubic feet per minute, ACFM. Eductor manufacturers generally present suction capacity data in terms of standard cubic feet per minute, SCFM, of air. When expressed in this manner, the capacity of a given eductor is strongly related to the eductor inlet pressure, discharge pressure and vacuum. However, if the data supplied by manufacturers for capacity in SCFM are converted to ACFM, the eductor suction capacity is relatively independent of eductor vacuum. Selection of said eductor inlet pressure and a rough estimation of the required discharge head then establishes its suction capacity in ACFM. From this data, values for the transport rate of the dry solid, solvation liquid feed rate to the nozzles, and solvation hopper volume can be estimated.
Laboratory and field testing of example apparatuses indicate that the transport rate of solids can be expressed by Equation 1.
T=C×D×E (1)
Where:
T=Solid transport rate, lb/min
C=Volume of solid per volume of eductor suction capacity
D=Solid bulk density, lb/ft 3
E=Eductor suction capacity, ACFM.
The value of "C" in the apparatus of this invention is usually 0.02 to 0.20 and more usually 0.05 to 0.10, and depends on the physical properties of the solid being transported. For example, free-flowing fine grained solids such as dense soda ash have a value of 0.085 while coarse material such as flake calcium chloride have a value of 0.07 in an example apparatus of this invention.
The quantity of solvation liquid required to ensure smooth operation depends on the size of the solvation hopper, e.g., the larger the solvation hopper the more surface area available for accumulation of hydrates; the orientation of nozzles; and on the dry chemical being handled. For nonhydratable dry chemicals such as activated carbon and sodium bicarbonate, smooth operation may be obtained without solvation liquid being supplied from nozzles, although it is preferred that a small quantity be provided to keep the wall member 9 of the solvation hopper clean. For hydratable dry chemicals, e.g. soda ash, handled with the apparatus of this invention, Equation 2 provides a relation for the estimation of flow rate of solvation liquid required when the solvation hopper is sized as described below. ##EQU1##
The required flow rate of solvation liquid fed to nozzles 7 will be in the range of 0.10 to 4 times the quantity "Z" and preferably in the range of 0.5 to 2 times the quantity "Z". Equation 2 and Equation 1, therefore, together determine the flow rate of said liquid. In this regard, low pressure at nozzles 7, e.g. 60 PSIG or less, will require flow rates on the high side of the range and high pressure at nozzles 7, e.g. 140 PSIG or more, will require flow rates on the low side of the range.
The solvation hopper formed by wall member 9 and inlet end member 6 should have a volume such that the nominal residence time of the solvation liquid in the hopper, i.e. the volume of the hopper divided by the solvation liquid flow rate, is from 0.5 to 30 seconds and preferably in the range of 0.5 to 10 seconds.
The solvation liquid and the eductor liquid are selected for compatibility with the transported chemical and the intended use of the chemical. In many cases, just a solvent, for example water, can be used as both liquids. If a slurry of a soluble chemical is desired on the other hand, it may be advantageous to employ a saturated solution of the chemical as the solvation liquid, the eductor liquid, or both.
The conduit from the apparatus to the dry chemical container may be any diameter hose, pipe or tubing but is preferably of the same diameter as the eductor suction fitting.
The following examples demonstrate the utility of the invention for transporting soda ash and calcium chloride using water or saturated solutions. These examples illustrate the adjustment of various process parameters for a single system, and should not be considered to limit the scope of the invention to particular chemicals, solvation liquids, or eductor liquids.
EXAMPLE #1
A laboratory scale apparatus using a 1" eductor for vacuum development was used to pull soda ash from a storage hopper, pneumatically convey the soda ash to the solvation hopper of an apparatus according to the invention, hydrate the soda ash, and transfer the resulting solution and slurry to a storage tank. The apparatus used had a solvation hopper volume of 1/8 gallon and a one-inch diameter inlet pipe. Two nozzles were used to supply solvation liquid to the solvation hopper in a tangential manner.
Conditions of operation were as follows:
______________________________________Eductor Suction capacity 2.8 ACFM at conditions statedEductor Liquid Saturated Soda Ash SolutionMotive Pressure 60 PSIGApparatus Discharge Pressure 5 PSIGEductor Liquid Flow 9 gpmSolvation Liquid Flow 1.7 gpm (0.11 gal/lb solid)Soda Ash Handling Rate 15.2 lbs/min (0.45 ton/hour)Soda Ash Bulk Density 64 lbs/ft.sup.3______________________________________
The apparatus and operating conditions provided smooth operation without adverse hydration and plugging of the system.
EXAMPLE #2
The apparatus described in Example #1 was used to pull soda ash from a hopper, pneumatically convey the soda ash to the apparatus, hydrate the soda ash, and transfer the resulting solution and slurry to a storage tank. Conditions of operation were as follows:
______________________________________Eductor Suction Capacity 3.3-ACFM at conditions statedEductor Liquid Saturated Soda Ash SolutionMotive Pressure 60 PSIGApparatus Discharge Pressure 3 PSIGEductor Liquid Flow 9 gpmSolvation Liquid Flow < 1 gpmSoda Ash Handling Rate --Soda Ash Bulk Density 64 lbs/ft.sup.3______________________________________
In this example the low solvation liquid flow caused the apparatus to plug with hydrated soda ash. Cleaning of the apparatus made determination of the soda ash handling rate meaningless.
This example demonstrates the need for solvation liquid flow within the range of the invention.
EXAMPLE #3
A laboratory scale apparatus using a 11/2" eductor for vacuum development was used to pull soda ash from a storage hopper, pneumatically convey the soda ash to an apparatus according to the invention, hydrate and dissolve the soda ash, and transfer the resulting solution and slurry to a storage tank. The apparatus used had a solvation hopper volume of 1/4 gallon and a one-inch diameter inlet pipe. Two nozzles were used to supply solvation liquid to the solvation hopper in a tangential manner. Conditions of operation were as follows:
______________________________________Eductor Suction Capacity 7.0 ACFM at conditions statedEductor Liquid WaterMotive Pressure 40 PSIGApparatus Discharge Pressure 3 PSIGEductor Liquid Flow 23 gpmSolvation Liquid Flow 2 gpm (0.049 gal/lb solid)Soda Ash Handling Rate 41 lbs/min (1.23 tons/hour)Soda Ash Bulk Density 64 lbs/ft.sup.3______________________________________
The apparatus and operating conditions provided smooth operation without adverse hydration and plugging of the system. This example demonstrate that the apparatus can be operated with water as well as saturated solutions of the chemicals (demonstrated in Example #1).
EXAMPLE #4
The apparatus described in Example #3 was used to pull soda ash from a hopper, pneumatically convey the soda ash to the apparatus, hydrate the soda ash, and transfer the resulting solution and slurry to a storage tank. Conditions of operation were as follows:
______________________________________Eductor Suction Capacity 8.0 ACFM at conditions statedEductor Liquid Saturated Soda Ash SolutionMotive Pressure 49 PSIGApparatus Discharge Pressure 3 PSIGEductor Liquid Flow 24 gpmSolvation Liquid Flow 4 gpm (0.10 gal/lb solid)Soda Ash Handling Rate 38 lbs/min (1.1 tons/hour)Soda Ash Bulk Density 64 lbs/ft.sup.3______________________________________
The apparatus and operating conditions provided smooth operation without adverse hydration and plugging of the system.
EXAMPLE #5
A large scale apparatus using a 3 inch eductor for vacuum development was used to pull soda ash from a railcar, pneumatically convey the soda ash to an apparatus according to the invention, hydrate and dissolve the soda ash, and transfer the resulting solution and slurry to a holding pond. The apparatus used had a solvation hopper volume of 2 gallons and a three-inch diameter inlet pipe. Four nozzles, disposed at an angle of 45° below horizontal, were used to supply solvation liquid to the solvation hopper in a tangential manner.
Conditions of operation were as follows:
______________________________________Eductor Suction Capacity 65 ACFM at conditions statedMotive Liquid waterMotive Pressure 100 PSIGApparatus Discharge Pressure 10 PSIGEductor Liquid Flow 200 gpmSolvation Liquid Flow 20 gpm (0.05 gal/lb solid)Soda Ash Handling Rate 400 lbs/min (12 tons/hour)Soda Ash Bulk Density 64 lbs/ft.sup.3______________________________________
The apparatus and operating conditions provided smooth operation without adverse hydration and plugging of the system. This example demonstrates the feasibility of unloading railcars of hydratable chemicals and transferring slurries and/or solutions of said chemicals to storage.
EXAMPLE #6
The apparatus of Example #5 was used to pull flake calcium chloride from a railcar, pneumatically convey the calcium chloride to an apparatus according to the invention, hydrate and dissolve the calcium chloride and transfer the resulting solution through approximately 250 feet of 4 inch piping to a storage tank. Conditions of operation were as follows:
______________________________________Eductor Suction Capacity 71 ACFM at Conditions StatedMotive Liquid WaterMotive Pressure 140 PSIGApparatus Discharge Pressure 25 PSIGEductor Liquid Flow 230 gpmSolvation Liquid Flow 34 gpm (0.126 gal/lb solid)Calcium Chloride HandlingRate 270 lbs/min (8 tons/hour)Calcium Chloride BulkDensity 55 lbs/ft.sup.3______________________________________
The apparatus and operating conditions provided smooth operation without adverse hydration and plugging of the system. Samples taken at locations along the discharge piping indicated that complete dissolution of the flake occurred in five seconds or less after the solvation liquid and solids exited the apparatus. This example demonstrates the feasibility of unloading railcars of hydratable chemicals and of transferring solutions of said chemicals to storage.
The trial runs using pilot and full scale systems described in the Examples demonstrate the ability of the apparatus and method according to the invention to effectively transport and hydrate, slurry and/or dissolve a dry hydratable chemical without plugging problems. The simple nature of the apparatus facilitates easy and inexpensive installation. Furthermore, the apparatus can be used to remove dry material from essentially any storage container withut requiring more than a compatible connecting device. Thus, the method of the apparatus is substantially superior to existing methods for unloading railcars which may require the construction of special structures or the digging of a pit under the track.
In the course of the trial runs it was also found that not all of the surfaces within the hopper were readily washed by flow from the nozzles. In particular, the chemical inlet pipe proved difficult to adequately wash with solvation liquid, although it was wetted. For this reason, hydrates tended to build up on the inlet pipe and cause plugging.
To overcome this problem one could in principle incorporate more nozzles oriented in appropriate directions. We, however, have found that it is preferable to utilize a non-stick material, such as polytetrafluoroethylene, in fabricating at least the exposed surfaces of the inlet pipe. The use of similar materials in fabricating the remainder of the hopper does not appear to be economically justifiable, since the nozzles are effective and since the non-stick material may be prone to abrasion. | An apparatus for the transfer of a dry chemical is formed having a sealed solvation hopper positioned between a liquid driven eductor and a fitting for connection to a storage container, e.g. a railcar. At the inlet end of the solvation hopper is a chemical inlet pipe which connects the interior to the exterior of the hopper. Surrounding the chemical inlet pipe are a plurality of nozzles for the introduction of solvation liquid into the hopper. The nozzles are disposed such that the solvation liquid washes the interior surface of the hopper to prevent plugging by hydrates (solvates) which may be formed. At the outlet end of the hopper, the hopper is connected to the suction opening of a liquid eductor. In use, the exterior end of the chemical inlet pipe is connected to the dry chemical storage container. Liquid flowing through the liquid eductor creates a suction and draws dry chemical out of the storage container and into the hopper. In the hopper, solvation liquid is supplied through the nozzles to wet the dry chemical and to wash the surfaces of the hopper, pushing the wetted material toward the outlet end of the hopper. At the outlet end of the hopper, the wetted material is sucked out into the eductor where it is combined with the flow of eductor liquid. The material leaving the eductor is recovered and sent either to storage or directly for processing. | 1 |
BACKGROUND OF THE INVENTION
The instant invention relates to easy open end closure members for containers and the like. More particularly, it is concerned with providing a depressible tab for can end closures that includes a nose portion wherein an improved pressure relief means in the form of a unique vent notch is incorporated in the nose structure of the tab.
Significant problems involved in the construction and use of depressible or push button tabs for beer and effervescent beverage containers and the like concern the controlled relief of internal pressures and the venting of the individual container's contents to the atmosphere during initial opening of the can or container equipped with such tabs so as to avoid undesirable outward spraying and splattering, frothing and foaming of the container's contents.
In an attempt to avoid the aforesaid problems it has been proposed in the past to use a pair of differentially sized openings in a can top which are covered by depressible push buttons, the smaller opening and its associated push button comprising a pressure release and vent opening and the larger opening comprising the pouring opening. The smaller push button is adapted to be opened first because it requires less force. This type of prior art push button or depressible tab container end is illustrated, for example, in U.S. Pat. Nos. 3,902,627; 3,958,717; 3,972,445; 4,033,275; Design Pat. Nos. 226,171 and 233,137 and British Patent Specifications Nos. 1,357,468 of June 19, 1954, and 1,407,806 of Sept. 5, 1975.
It has also been suggested that such prior art small vent openings be incorporated in the principal or large depressible tab structure of an easy open can as evidenced, for example, by the teachings of U.S. Pat. Nos. 3,741,432 and 3,794,206 as well as German Offenlegungsschrift No. 2,421,314 published Nov. 14, 1974. In these instances the smaller depressible tab is adapted to be hingedly connected to the main or larger depressible tab of which it forms a part.
SUMMARY OF THE INVENTION
The instant depressible tab constitutes an improvement over the aforesaid prior art easy open tabs by utilizing a single depressible tab and providing the tab with a unique notched nose portion for controlably relieving the internal pressures generated by the contents of the can or container with which the tab is associated during the initial opening of the container so as to avoid the aforementioned undesirable and sometimes disasterous outward spraying, frothing, foaming and content loss.
The use of a single depressible tab provided with the improved venting arrangement proposed permits use of the same finger element to initiate and subsequently complete the uncovering of the container's pour opening. This is accomplished by the same finger firstly being pressed against the nose portion of the depressible tab to initiate tab and container separation and to expose the pressure release vent notch to the atmosphere. This action can then be followed by a shifting or transfer of force through the medium of the same finger to the main body portion of the tab to obtain full displacement of the tab and a complete uncovering of the pour opening.
In a preferred embodiment of the invention the notched nose portion of the depressible tab can be advantageously provided with ribbed embossments or the like so as to reinforce the notched nose and inhibit malfunctioning of the tab in the initial uncovering of the singular combination pressure release, air vent and pouring opening. In short, structuring of the tab nose portion in this manner helps to concentrate container opening forces in the area of the vent hole or notch during initial tab and container separation while at the same time simplifying the procedures for manufacturing such tabs. The instant tab design also avoids the problems of accidental damage to the small hinge element for the small depressible tabs mounted in or connected to main or large depressible tabs such as are proposed and illustrated in U.S. Pat. Nos. 3,741,432 and 3,794,206 and over which the instant development constitutes an improvement.
The depressible tab of the instant invention also constitutes an improvement over the single depressible tabs of U.S. Pat. Nos. 3,982,657; 3,980,034; 2,261,117; 3,905,513; 1,878,677; 3,881,437 and 3,843,011, as well as the other depressible tab developments of U.S. Pat. Nos. 3,410,436; 3,779,417; 3,760,752; 3,886,199; 3,334,775; 4,006,700; 3,286,874; 3,931,909; 4,018,178 and Design Pat. No. 208,591.
A preferred embodiment of the invention contemplates that during manufacture at least the nose portion of the depressible tab be completely severed from the end closure panel per se with which it is associated. This permits the nose portion which can comprise a small or large section of the tab to be advantageously overlapped and locked in position by the end closure panel either by virtue of flattening and expanding at least the nose part of the tab in the manner disclosed in U.S. Pat. No. 4,033,275 or by shrinking the end closure opening about at least the nose of the tab in the manner discussed in U.S. Pat. No. 3,931,909. After the desired selected overlapping of tab nose and panel has been completed the line of severance between the end closure panel and the tab nose portion is subsequently sealed by the application of an appropriate plastic sealant patching material in the manner noted, for example, in U.S. Pat. No. 3,931,909, such as by means of a plastisol material sold under the designation "Plastisol 911" by the Dewey and Almy Chemical Division of W. R. Grace and Company of San Leandro, California.
In the ensuing discussion it is to be understood that the terms "closure member" or "end closure" as used throughout the specification and claims are meant to include closures made from various types of appropriate material such as aluminum and its alloys, steel, tin plate, and other metals which are suitable for manufacturing the container closures as well as container closures made of these metals provided with relatively thin plastic films and coatings well known in the art and customarily used to protect the closure metal against the contents of the containers and vice versa and container closures of other than circular configurations.
BRIEF DESCRIPTION OF DRAWINGS
FIG. 1 is a top plan view of a container end closure provided with the improved depressible tab of the instant invention;
FIG. 2 is a partial cross-sectional view of the container end closure of FIG. 1 when taken along the line 2--2 thereof and with a modified form of nose reinforcement being shown;
FIG. 3 is an enlarged cross-sectional view of a portion of the container end closure of FIG. 1 when taken along line 3--3 thereof;
FIG. 4 is a fragmentary bottom plan view with parts removed and other parts added of the portion of the sealant covered underside of the container end closure of FIG. 1 that contains the depressible tab and with the severed and tab overlapping panel portions being shown in dotted lines, with the tab being somewhat reduced in size and provided with modified embossments from that shown in FIG. 1;
FIG. 5 is a fragmentary top plan view of another container end closure and discloses a further embodiment of the depressible tab of the instant invention;
FIG. 6 is a fragmentary cross-sectional view of the end closure of FIG. 5 when taken along line 6--6 thereof and illustrates a step that can be used, if desired, in the production process for the tab of FIG. 5 wherein the hinge portion of the tab is first bulged outward;
FIG. 6(a) is a view similar to FIG. 6 after the bulged tab hinge portion has been flattened to enhance the overlap between the nose portion of the tab and the panel area surrounding the tab opening;
FIG. 7 is a fragmentary bottom plan view of the portion of the sealant covered underside of the end closure of FIG. 5 that contains the depressible tab and illustrates how an endless ring of sealant material covers the line of demarkation or separation between the main panel of the end closure and the depressible tab per se as well as the tab hinge; and
FIG. 8 is a fragmentary perspective view of the reinforced and notched nose portion that can be used with the depressible tab of FIG. 1.
DETAILED DESCRIPTION
With further reference to the drawings and in particular FIGS. 1 through 4, one embodiment of the invention contemplates that the depressible tab 10 would be utilized with an end closure 12 made of a suitable aluminum alloy, e.g., 5182, the number designated for the same by the American Aluminum Association and of the proper temper and with an original thickness of about 0.013 inch. Each closure 12 is provided with the standard outer peripheral reinforcing rim 14 which is adapted to be lock-seamed in the usual fashion to the top of a container such as a beverage or beer container. Closure 12 further includes the usual reinforcing rib or counter sink 16 and a central or main panel or area 18.
Tab 10 can take various configurations or shapes such as the teardrop shape of the drawings, or it can be rectangular, oblong or elliptical, etc. Tab 10 includes the normal hinge section 20 that can be small as indicated in drawings or it can be larger. This hinge section can also be located in close proximity or adjacent to the counter sink 16. Hinge section 20 is formed integrally with the main panel 18 and serves to retain depressible tab in contact with the panel after it has been depressed the desired amount.
Score lines 22 eminate from opposite sides of the hinge 20 and these score lines may be simple score lines impressed on one side of the end closure 12 or they may take the form of the double scores shown in FIG. 3 wherein the scoring takes place on both sides of the end closure 12 and as shown in U.S. Pat. Nos. 3,902,627 and 3,982,657. Thus the tab is further delineated by a thinned and embrittled area or web 23 defined by the score lines 22 and bounded on each side by the stepped portion 24 of the tab and the stepped portion 26 of the main panel 18. Embrittled section 22 can be readily fractured to complete the final separation of tab 10 from the remainder of the panel 18 except for hinge portion 20 once the opening of the depressible tab is initiated as set out hereinafter. The weakened webs or scored areas 23 project for a preselected distance away from and on both sides of hinge 20 until they tend to converge such as adjacent the central axis of the panel 18 and merge with notched nose portion 19 of tab 10.
Nose portion 19 is formed in the sector A of the panel 18 of FIG. 1 by being first completely severed from panel 18 in this sector A and then being overlapped by the portions 25 of the panel 12 located adjacent to or defining the line of severance between the panel and nose portion. This overlapping can be effected by forming a bulge in the tab nose and then pushing the tab nose down into the opening and subsequently expanding the nose 19 in the manufacturing process in the manner described in U.S. Pat. No. 4,033,275; or by pushing the tab nose down into the opening 27 formed by severance of the nose from the panel 12 and then collapsing or stretching the overlapping portion 25 of the panel surrounding and defining opening 27 to shrink the size of opening 27 in the manner discussed in U.S. Pat. No. 3,931,909.
Nose 19 is provided with the unique venting notch or opening 30 and although only one such notch, which can be V-shaped, is shown it is obvious that other notch configurations or cuts may be employed as well as multiple notches. The nose 19 may be advantageously stiffened and reinforced by suitable embossments such as by means of the finger engaging button 31 of FIG. 2 or the Y-shaped ribbing 33 of FIGS. 1, 4 and 8.
After tab nose portion 19 is selectively overlapped by panel opening surround or free edge 28 of panel portions 25 to the point that the notch 30 is preferably fully covered by the overlapping metal of panel portions 25 it can be sealed in place. The underlying part of nose 19 is sealed to the end closure 12 by the application of a sufficient amount of plastisol sealant patching material 32 of the type previously described to the area of overlap and severance between nose 19 and panel 18 whereby a substantially complete seal is effected between tab and panel and with notch 30 being preferably completely filled with the sealant material to minimize accidental opening and venting of the end closure until the desired time.
If desired, the excess metal resulting from forming the thinned web 23 can be advantageously absorbed in a further reinforcing embossment 40 of the type shown in FIG. 1 or in an extension of the base leg of the Y-shaped embossment 33 shown in FIGS. 1, 4 and 8.
It is to be understood that the embossments 31, 33 and 40 should be of such an appropriate height that they still would be protected by the rim 14 of the end closure even when rim 14 is partially collapsed and seamed to a can. As further protection for tab 10 and the embossments thereof additional appropriate upstanding embossments 50 only two of which are shown in FIG. 1 can be formed in panel 18. These latter embossments 50 are used to protect the tab and prevent accidental opening of the same during the usual seaming of the end closure 12 to a metal container such as a beer or beverage can as well as during a further end closure mechanical handling and stacking operation.
A further advantageous embodiment of the invention is disclosed in FIGS. 5 through 7. In this instance prime numerals are used to identify parts similar to those of FIGS. 1 through 4. Thus the depressible tab 10' can likewise have a somewhat teardrop shape with the hinge portion 20' integral with panel 18' also being preferably located in close proximity to the counter sink 16'. Except for hinge portion 20' tab 10' is completely and continuously severed from panel 18' along the free surround edge 28° which merges with the hinge portion 20' at the opposing extremities thereof. The severed tab can then be pushed through the opening 27' formed by the severance of tab 10' from panel 18' and expanded or enlarged in the manner described in U.S. Pat. No. 4,033,275 to form the desired overlap between tab 10' and panel 18' along the periphery of the tab 10' and the overlapping panel portions 25' extending from hinge 20'. Alternatively the overlap of the tab 10' and panel 18' can be effected as in the case of the tab nose of FIG. 1 by the manufacturing steps described in U.S. Pat. No. 3,931,909 which includes the step of reducing the size of closure opening 27' by collapsing or stretching the overlapping panel portions 25' of panel 18' surrounding the opening 27'. In any event regardless of how the overlap of tab 10' and panel 18' is effected it should preferably be sufficient at nose portion 19' to substantially fully cover the vent notch 30' formed in the nose portion 19' during manufacture on one side of panel 18'.
As in the case of the tab 10' of FIG. 1, a line of sealant 32' is then applied to the other or underside of panel 18' and along the entire periphery of the tab 10' including, if desired and as indicated in FIG. 7, the hinge portion 20'. Thus the sealant can be applied as a full unbroken ring of sealant having the appropriate width and thickness. This sealant also preferably fills the notch 30' of nose 19' in the same fashion as with the tab of FIG. 1 to form a final positive seal between tab 10' and panel 18' until the tab is depressed by the application of pressure first to the nose portion 19' to effect initial fracture of the sealant in the area of the nose portion 19' along with the initial separation of panel 18' and tab 10' and a controlled release of the interior pressure of the container provided with the tab. If desired, the tab 10' of FIG. 5 can also have the same notch features and nose reinforcements as those of the tab 10 of FIG. 1.
In a further advantageous embodiment of the invention and as indicated particularly in FIGS. 6 and 6(a) in those instances where the tab 10' is fully severed from the panel 18' except in the hinge area 20' this hinge area on the panel 18' can be somewhat bulged in the manner indicated in U.S. Pat. No. 3,980,034 during the initial steps of tab and panel severance and notching of the nose portion in the manufacturing operation. Thereafter this bulged area of the panel 18' is flattened or collapsed into the final hinge 20" and upon flattening forces the notched nose 19' to be additionally selectively overlapped in the offset manner shown in FIG. 6(a) to obtain an extended overlap and seal between panel 18' and nose 19'.
While FIGS. 1, 4 and 8 disclose how the bifurcated nose portion 19 of the tabs of FIGS. 1 and 4 can be reinforced or stiffened to insure initial fracture of the sealant and controlled release of pressure in the area of the nose portion of a depressible tab by Y-shaped ribbing, it is to be understood that such ribbing could be extended to the edges of the nose 19 if desired. Finally, depending on the particular configuration adapted for the depressible tab and the results desired the tab can be so oriented on an end closure panel 18 or 18' such that the hinge portion 20 or 20" of the tab is located remote from the counter sink or rim portion of the end closure rather than adjacent thereto and the notched nose portion located adjacent the center of the panel 18 or the most neutral point on the panel should a can provided with the instant tab be tilted during opening.
In those instances where during tab manufacture only the nose portion of the tab is completely severed from the end closure panel while the remainder of the tab periphery exclusive of the tab hinge is defined by a score line as in the case of the tabs of FIGS. 1 and 4, care should be exercised to provide for the desired tab force advantage to initiate tab and sealed panel separation without great difficulty. Thus a preferred embodiment of the invention contemplates in the aforesaid instances that the full panel and tab severance line in the sector A comprise between about one-fourth and one-third of the overall outer periphery of the tab exclusive of the hinge portion thereof.
Advantageous embodiments of the invention have been shown and described. It is obvious that various changes may be made therein without departing from the spirit and scope thereof as defined by the appended claim wherein: | Improved depressible tab provided with a nose for easy open end closure members and the like, wherein an improved pressure relief means in the form of a unique vent arrangement is incorporated in the nose portion of the depressible tab. | 1 |
TECHNICAL FIELD
[0001] The present invention relates generally to fixation devices used in orthopedic surgery. This invention relates more particularly to devices used for cervical posterior fixation by means of a plate attached to a bone in the occipital region and secured to a rod which attaches to a cable, wire, plate, or screw fastened in the spinal region.
BACKGROUND
[0002] Fixation devices are used in orthopedic surgery to stabilize bones such as those in the spinal column. One type of fixation device includes a plate attachable to a portion of a bone. The plate may be connected to another bone or another portion of the same bone, directly or through other connecting devices. For example, posterior fixation devices can include a plate fastened to the skull, or occiput, one or more rods running longitudinally along the spine and connected to the plate, and plates, cables, wires, hooks, screws, or other connectors attached to a vertebra and connected to the rod.
[0003] A number of such mechanisms are known in the act. To accommodate the variation in patient size and anatomy, a plate often needs to be chosen from a set of plates of multiple sizes and/or varying geometry. This results in a higher cost of the device assembly and a need to maintain separate inventory of the various size and geometry devices. It also increases the surgical time because the surgeon must search for the device that best fits the patient. Accordingly, there is a need for an improved fixation plate.
SUMMARY
[0004] A fixation device for connecting a stabilization device to a bone comprises a first member comprising a first portion for attachment to a bone; a second member comprising a second portion for attachment to a bone and connected to the first member by a pivotal connection such that the first and second portions are spaced apart by an adjustable distance, at least one of the first and second members further comprising a portion for mounting a connector adapted to secure a stabilization device
[0005] A method of attaching a stabilization device to a bone comprises attaching a first plate to a bone at a first portion on the first plate; attaching a second plate, pivotally attached to the first plate, to a bone at a second portion on the second plate; pivotally adjusting the position of the second plate relative to the first plate to adjust the distance between the first portion and the second portion; and attaching a stabilization device to either the first plate or the second plate.
[0006] While multiple embodiments are disclosed, still other embodiments of the present invention will become apparent to those skilled in the art from the following detailed description, which shows and describes illustrative embodiments of the invention. As will be realized, the invention is capable of modifications in various obvious aspects, all without departing from the spirit and scope of the present invention. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not restrictive.
BRIEF DESCRIPTION OF THE DRAWINGS
[0007] FIG. 1 shows a variable geometry occipital device, according to one embodiment of the present invention.
[0008] FIG. 2 shows a perspective view of the variable geometry occipital fixation device of FIG. 1
[0009] FIG. 3 shows an exploded view of the variable geometry occipital fixation device of FIG. 1 .
[0010] FIG. 4 shows another exploded view of the variable geometry occipital fixation device of FIG. 1 after insertion of the attachment bosses.
[0011] FIG. 5A shows a top plan view of the variable geometry occipital fixation device of FIG. 1 in its narrowest configuration.
[0012] FIG. 5B shows a top plan view of the variable geometry occipital fixation device of FIG. 1 in its widest configuration.
[0013] FIG. 6 shows an exemplary method of using the variable geometry occipital fixation device of FIG. 1 .
[0014] While the invention is amenable to various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and are described in detail below. The intention, however, is not to limit the invention to the particular embodiments described. On the contrary, the invention is intended to cover all modifications, equivalents, and alternatives falling within the scope of the invention as defined by the appended claims.
DETAILED DESCRIPTION
[0015] FIG. 1 shows a variable geometry occipital device 10 in one embodiment of the present invention. The variable geometry occipital device 10 in this case is affixed to the occiput 2 of the patient 4 . One or more rods 6 are attached to the device 10 and run substantially along the spine column 8 and are attached to various segments of the spinal column 8 .
[0016] FIG. 2 shows a perspective view of the variable geometry occipital device 10 of FIG. 1 . The variable geometry occipital fixation device 10 includes a first lateral member 12 , a second lateral member 14 , and a midline member 16 . The first lateral member includes a proximal end 18 , a distal end 20 , and an attachment bore 22 located at the distal end 20 .
[0017] The second lateral member includes a proximal end 24 , a distal end 26 , and an attachment bore 28 located at the distal end 26 . The midline member includes a proximal end 30 and a distal end 32 . In the embodiment shown in FIG. 2 , the proximal ends 18 , 24 , and 30 are stacked on top of each other. Attachment bosses 34 are inserted into the attachment bores 22 and 28 . Each attachment boss 34 has a slot 35 for receiving a stabilization device such as a rod, a cable or a cord. The attachment boss 34 further has a threaded portion 76 for receiving a threaded fastener, such as a set screw, which can be tightened directly or indirectly (e.g., through a spacer) against the stabilization device to retain it in the slot 35 . Any other suitable connectors for securing stabilization devices can be used instead of the attachment bosses 34 to achieve the desired performance.
[0018] FIG. 3 shows an exploded view of the variable geometry occipital fixation device 10 of FIG. 1 . The first lateral member 12 includes the attachment bore 22 , a pivot bore 36 located at the proximal end 18 , and a fixation bore 38 interposed between the attachment bore 22 and the pivot bore 36 . A groove 40 is interposed between the proximal end 18 and the distal end 20 . The groove 40 facilitates bending of the first lateral member 12 so that it conforms to the occiput. In the embodiment shown in FIG. 3 , the groove 40 is located on a top surface 42 . The groove 40 could alternatively be located in any other suitable area. Alternatively, the first lateral member 12 could have more than one groove 40 , or no groove at all.
[0019] Similarly, the second lateral member 14 includes a pivot bore 44 located at the proximal end 24 , the attachment bore 28 located at the distal end 26 , and a fixation bore 46 interposed between the attachment bore 28 and the pivot bore 44 . A groove 48 is interposed between the proximal end 24 and the distal end 26 and is located on a top surface 50 . Alternatively, the groove 48 could be located in some other suitable area. The second lateral member 14 could include any appropriate number of grooves 48 .
[0020] The midline member 16 includes a proximal end 30 and a distal end 32 . A pivot bore 52 is located at the proximal end 30 and a fixation bore 54 is located at the distal end 32 . A groove 56 is interposed between the proximal end 30 and the distal end 32 and is located on a top surface 58 . The midline member 16 could include any appropriate number of grooves 56 located in any suitable area.
[0021] In the embodiment shown in FIGS. 1-3 , the pivot bores 36 , 44 , and 52 are aligned so that the first lateral member 12 and the second lateral member 14 rotate around a common axis 60 . The thickness 62 of the proximal end 18 of the first lateral member 12 is less than the thickness 64 of the distal end 20 . Similarly, the thickness 66 of the proximal end 24 of the second lateral member 14 is less than the thickness 68 of the distal end 26 . The thickness 70 of the proximal end 30 of the midline member 16 is also less than the thickness 72 of the distal end 32 . In this manner, when the three members 12 , 14 , and 16 are assembled together and installed in the patient 4 , the thickness of the occipital device 10 is substantially uniform across the members 12 , 14 , and 16 and the stacked portions of members 12 , 14 , and 16 . However, the invention is not limited to a device of such uniform thickness. The thicknesses 64 , 68 , and 72 need not be less than the thicknesses 66 , 70 , and 74 or be less by the same amounts as in this illustrative embodiment of the invention.
[0022] In the embodiment shown in FIGS. 1-3 , the fixation bore 38 in the first lateral member 12 is countersunk so that when a fastener (not shown) is inserted into fixation bore 38 , the height of the fastener protruding above the top surface 42 is minimized. The fixation bores 46 and 54 in the second lateral member 14 and the midline member 16 are also countersunk in a similar manner. Alternatively, some or all of the fixation bores 38 , 46 , and 54 need not be countersunk.
[0023] The three members 12 , 14 , and 16 can be attached to each other in a number of ways. In one embodiment of the invention, the members are swaged together so that they remain attached to each other while being handled but can be manipulated into different angular relationships to each other. Alternatively, the three members 12 , 14 , and 16 can remain separate until implantation into the patient 4 , when they become linked to one another by the insertion of a fastener (not shown) into the pivot bores 36 , 44 , and 52 . The fastener could be a rivet, screw, or any other suitable fastener.
[0024] FIG. 4 is a perspective and partially exploded view of the variable geometry occipital fixation device 10 of FIG. 1 after insertion of the attachment bosses 34 into attachment bores 22 and 28 . In the embodiment shown in FIG. 4 , the attachment bosses 34 are inserted into the attachment bores 22 and 28 . The attachment bosses 34 could be press-fit, riveted or swaged into the attachment bores 22 and 28 or inserted in any other suitable manner. The attachment bosses 34 preferably are free to rotate inside of the bores 22 and 28 so as to maintain the orientation of the stabilization device after the orientations of the lateral members 12 and 14 are adjusted.
[0025] FIG. 5A shows a top plan view of the variable geometry occipital fixation device 10 shown in a narrow configuration. As shown in FIG. 5A , the angle 78 between the lateral members 12 and 14 is relatively small, thereby reducing the distance 80 between the bosses 34 . The angle 78 can vary as needed achieve the desired distance 80 .
[0026] FIG. 5B shows a top plan view of the variable geometry occipital fixation device 10 shown in a wide configuration. As shown in FIG. 5B , the angle 78 between the lateral members 12 and 14 is larger than the angle 78 shown in FIG. 5A , thereby spanning a larger distance 80 between the bosses 34 than shown in FIG. 5A . In one embodiment of the present invention, the angle 78 is approximately 100 degrees when the distance 80 is minimized and is approximately 170 degrees when the distance 80 is maximized. The available range for angle 80 need not be limited to these angles, but instead can include any desirable range.
[0027] The first and second lateral members 12 and 14 and the midline member 16 can include any configuration of fixation bores, attachment bores, and pivot bores suitable for achieving the desired variability in the distance 78 between the attachment bores 24 and 38 . The number and the location of the fixation bores, attachment bores, and pivot bores can vary as needed.
[0028] FIG. 6 shows an exemplary method 200 of using the occipital fixation bracket 10 of the present invention. A first lateral member 12 and a first attachment boss 34 are provided (block 205 ). Then, a second lateral member 14 and a second attachment boss 34 are provided (block 210 ). The attachment bosses 34 are preferably inserted into the first and second lateral members 12 and 14 prior to surgery. A midline section 16 is also provided (block 215 ).
[0029] The second lateral member 14 is positioned in the desired location against the occiput (block 220 ). The first lateral member 12 is positioned against the occiput and overlying the second lateral member 14 so that the pivot bores 36 and 44 rotate around a common axis 60 (block 225 ). The midline member 16 is then positioned against the occiput and overlying the first lateral member 12 (block 230 ). The pivot bore 52 is aligned with the pivot bores 36 and 44 .
[0030] Next, fasteners are inserted through the pivot bore 52 and the fixation bore 54 of the midline member 16 and into the occiput, thereby attaching the midline member 16 to the occiput (block 235 ). The first lateral member 12 and the second lateral member 14 are rotated around the common axis 60 until the desired distance 80 between the attachment bosses 34 is achieved (block 240 ). The attachment bosses 34 are free to rotate in their bores 22 and 28 . The fasteners are then inserted into the fixation bores 38 and 46 of the first and second lateral members 12 and 14 , thereby fastening them to the occiput and fixing the position of the attachment bosses 34 (blocks 245 and 250 ). In this manner, the variable geometry occipital fixation device may be installed and adjusted to accommodate a variety of patient sizes and anatomy.
[0031] Various modifications and additions can be made to the exemplary embodiments discussed without departing from the scope of the present invention. Accordingly, the scope of the present invention is intended to embrace all such alternatives, modifications, and variations as fall within the scope of the claims, together with all equivalents thereof. | A fixation device for connecting a stabilization device to a bone comprises a first member comprising a first portion for attachment to a bone; a second member comprising a second portion for attachment to a bone and connected to the first member by a pivotal connection such that the first and second portions are spaced apart by an adjustable distance, at least one of the first and second members further comprising a portion for mounting a connector adapted to secure a stabilization device. | 0 |
BACKGROUND OF THE INVENTION
[0001] Large structures and machines are frequently made from many parts and components. These structures include but are not limited to aircraft, ships, machines and buildings. In many of these structures, there are large components subject to such vicissitudes of time as wear, fatigue, corrosion, stress, and strain. When such a component must be replaced, the process can be very costly and time-consuming. The structure has “worn-in,” and some of the components have become distorted from their as-manufactured or as-installed condition. These changes mean that a part from the manufacturer, as originally designed and manufactured, may no longer fit precisely into the structure. A user may have some difficulty using a replacement part from the manufacturer, even if it is forced into place.
[0002] The differences between similar parts may be small as a percentage of the length or girth of the part, but may be large enough to present difficulties upon assembly. The situation may then be exaggerated as structures “wear in” and absorb stress over time. Plastic deformation and strain may result in considerable differences between a part as installed and a part after several years' service. As a result, dimensional data or drawings from a manufacturer of the part may not be consistent with the needs of the end-item owner after several years. In other words, parts made by the manufacturer from design and manufacturing data may not fit into individual structures or end-items. These structures are not limited to aircraft, but may include ships, portions of buildings or other civil structures, submarines, large machines, and the like.
[0003] One way around this difficulty is to hand-fit a replacement part, tailor made to fit exactly into place. Such hand-fitting may be accomplished by custom manufacturing, using templates and detailed labor to replicate the actual needed fit. In one such hand-fitting, thin sheets of hard plastic are laid over the structure in need of repair, and marked, trimmed and drilled to replicate exactly the old part. Besides being very costly and time-consuming, such methods are prone to error. Thus, a feature not placed correctly or a hole placed too near an edge may result in a ruined replacement part. A feature may be any real or imaginary portion or location on a structure, such as a hole, a length, a boss, a rib, an edge or a datum.
BRIEF SUMMARY OF THE INVENTION
[0004] The invention is a method for repairing a structure or a portion of a structure. The method includes setting up a measuring device to measure the part or portion to be repaired. The device is desirably a multi-axis measuring machine, having linear axes or rotary axes of motion. In one sense, the measuring device may be very similar to a coordinate measuring machine (CMM) or a computer numerically-controlled (CNC) machining center, in that it desirably possesses a plurality of axes with which it may quickly and efficiently measure the desired features and contours of the device or portion requiring repair. The device is set-up and oriented so that the measuring device may measure and digitize data for the portion to be repaired with respect to the structure of which it is a part.
[0005] The device then measures the appropriate portion and stores the data in a convenient format. The data may be saved to an internal drive or storage medium, such as a hard drive or a disc, or it may be immediately transferred to an external drive or storage medium, or even another computer. The data is then used to program at least one machine tool and automatically manufacture the needed repair part. The method will work for parts in three dimensions, that is, parts requiring a length, width and depth, or parts in three dimensions that may be more conveniently measured in spherical or cylindrical coordinate systems rather than linear (Cartesian) systems. The part may then be installed.
[0006] In another method of practicing the invention, the portion of a structure requiring repair is a sheetmetal or two-dimensional part, such as a bulkhead of an aircraft or a ship. The measuring device is set up and oriented near the bulkhead. The device then measures the portion to be repaired and saves the data. The data is then used to automatically manufacture a sheetmetal repair part, the data driving one or more tools on a machine tool working the sheetmetal repair part. The repair part is then installed on the structure requiring repair.
BRIEF DESCRIPTION OF SEVERAL VIEWS OF THE DRAWINGS
[0007] [0007]FIG. 1 depicts an exemplary aircraft structure in need of repair.
[0008] [0008]FIG. 2 is a magnified view of an area where a bulkhead has been removed and must be replaced.
[0009] [0009]FIG. 3 is a mount suitable for use in measuring a structure.
[0010] [0010]FIG. 4 depicts a measuring machine suitable for measuring a structure.
[0011] [0011]FIG. 5 describes a process for repairing a structure
[0012] [0012]FIG. 6 depicts an operator using a measuring machine to orient the measuring machine with the area in need of repair.
[0013] [0013]FIG. 7 depicts an operator using a measuring machine to orient the measuring machine with the structure.
[0014] [0014]FIG. 8 depicts an operator using a measuring machine to measure the periphery of a portion in need of repair.
[0015] [0015]FIG. 9 depicts a nesting sequence of parts required for the repair.
[0016] [0016]FIG. 10 depicts a replacement part being machined in an operation on a CNC router.
[0017] [0017]FIG. 11 depicts a replacement part being formed in another operation.
DETAILED DESCRIPTION OF THE INVENTION
[0018] [0018]FIG. 1 depicts an aircraft 10 having a bulkhead 12 in need of repair. In this depiction, the bulkhead area is forward on the aircraft and a radome (not shown) has been removed so that repair technicians and mechanics may remove the bulkhead. It will be appreciated that in many cases, such parts bear similarity to parts on other aircraft, for instance other aircraft of the same type and model made by the same manufacturer. While the parts may be very similar, however, each individual aircraft's parts may be slightly different, especially in very large structures. In other words, there may be small differences on each particular aircraft, structure, machine, or building, the differences arising at their inception or later, even though each is nominally the same as all others of the same make, model, type or class.
[0019] [0019]FIG. 2 depicts an area of the aircraft where a replacement bulkhead is needed, and shows the underlying structure into which the bulkhead must fit. The bulkhead manufactured must match the periphery 14 and bolt up with horizontal members 16 such as stringers and T-bars, vertical members 18 , and reinforcing members 20 . In matching a part to these elements, it is also important to note the position of aircraft alignment holes 22 , features with a known location and orientation. It is this area into which the replacement part must fit, and whose dimensions may have changed over time and over use.
[0020] [0020]FIG. 3 depicts a mounting bracket useful for mounting a measuring device in proximity to the area where measurements are needed. The mounting bracket 30 has a vertical member 32 for mounting to the structure via pads 38 . Gussets 36 may support a horizontal member 34 in order to mount a measuring device. Such a measuring device is depicted in FIG. 4. The measuring device may be a multi-axis coordinate measuring machine 40 , having a base 42 and at least one linear axis 44 , and preferably having at least one rotary axis 46 , and a probe 48 . A preferred device, available from Faro Corp., Lake May, Fla., is a model Faro Gold Arm measuring device. It has 6 axes of motion, three linear and three rotary. The measuring device is mounted on the bracket and oriented with plumb lines in at least one plane. Plumb bobs are suitable for this orientation.
[0021] In accordance with the present invention, FIG. 5 describes a process for repairing a structure using a measuring device such as the Faro arm. In this embodiment, a user sets up a mounting bracket for the measuring device 100 , as near as convenient to the structure needing repair. The use then mounts the Faro arm on the bracket 110 . In one embodiment, the user then turns on the machine, installs the probe, and calibrates the machine and probe 120 . Probes may be tangible objects, such as a standard Renishaw probe for a coordinate measuring machine (CMM), or they may consist of laser probes, using a light beam rather than a physical touching of the object being measured. The user than aligns the machine and probe 130 with respect to the structure being repaired.
[0022] With the measuring device oriented with respect to the structure, the measuring process may be performed, measuring features and storing the data in a computer or peripheral memory. The user manipulates the probe to measure all features needed for reproducing the part needing repair, such as the center points of holes 140 , and their other necessary dimensions. It may be necessary to guide the probe around the periphery or boundaries of a part 150 if the part is not readily described in geometrical terms, or if the part has “settled in” sufficiently to require customizing. Once all measurements are taken, the user gathers the saved data and may perform sufficient tests to guarantee its integrity 160 . The file or data are then exported from the measuring machine 170 to begin manufacturing a part. In some cases, other data, such as features not requiring measuring, may be added 175 . The data is preferably available from one or more computer programs or files available to the user. In some cases, process planning for conventional manufacturing processes 180 will be necessary. Process plans or manufacturing instructions are prepared and the repair parts are manufactured 185 . The repair parts are then installed 190 .
[0023] In one embodiment of the process, reference features for orienting the measuring device are provided on the structure itself. For example, in the Boeing 737 , the station 178 bulkhead has two orienting rivet holes just forward of the bulkhead and on the bottom skin of the aircraft to orient the user. Other structures may use other data (datums) or points for orientation. In the case of a bulkhead in need of repair, the bulkhead having a largely planar structure, the plane of the bulkhead bottom may be defined by recording reference points with the measuring device. The subject of orientation of measuring devices is well known to those is mensuration arts and will not be repeated here.
[0024] It is not strictly necessary for the method to use a mount and a measuring machine mounted as shown in FIGS. 3 and 4. Any automatic measuring technique may be used; however, a relatively small and mobile measuring machine is convenient and quick. A user may also use variations of the method, however, such as moving the part or structure to a CMM or moving a CMM conveniently near the structure.
[0025] [0025]FIG. 6 depicts an operator manipulating the measuring device and its probe 48 to measure the alignment holes and record their location. FIG. 7 depicts a user manipulating an axis 42 of the measuring device and the probe 48 to take reference points establishing the plane of the bulkhead. Exemplary of probes are those made by Renishaw plc of Gloucestershire, United Kingdom.
[0026] Once the measuring device is oriented, a user may then begin the measuring process. FIG. 8 depicts an operator manipulating the measuring device to scan in the periphery of the bulkhead. Every other feature desired may also be measured and scanned in. Not every feature of the replacement part need be so measured or scanned. In the present example, the replacement bulkhead must have holes drilled to match every hole in the underlying structure where a fastener is desired. Other features may include, but are not limited to, cut-outs, pockets, slots, and chamfers. Even a relatively planar bulkhead may require fasteners, and thus holes, drilled at an angle. The measuring process may take all data in three dimensions using every axis available on the measuring device. For example, every hole may be measured using its diameter or radius, the angle desired with the surface of the bulkhead (if not perpendicular), and even the depth of the hole, such as for a blind hole that must be drilled and tapped later. Chamfers and lead-ins may also be measured if needed.
[0027] While a measuring arm and a probe are useful for measuring the structure and gathering data, other means may be used. Another apparatus that has been found useful is a laser scanner used with special software. With this device, dimensions are measured quickly and easily, and the data is recorded for later use. Equipment and software useful for this purpose is available from NVision, Inc., of Dallas, Tex. A laser scanner allows a user to take the application from a part requiring repair to a machine tool or other implement capable of making a repair part. Such machine tools may include multi-axis machining centers, including but not limited to, 3-, 4-, 5- and 6-axis machining centers. Laser scanners reduce the time needed to scan in the data from a part or a structure, particularly when the part requiring repair is large, or when the part is complex, especially in terms of dimensional complexities such as compound curvatures and the like. In some instances, a laser scanner may be able to access areas of structures better than a probe.
[0028] In using such a laser-scanning device, a process for repairing a structure includes mounting the device, preferably on a multi-axis coordinate measuring machine. The device is then oriented, and the part to be repaired is measured. The data is then saved and used to manufacture a repair part.
[0029] Preferably, data is taken with consideration of the processes to be used for manufacturing the repair parts. If the bulkhead has a flange or other portion in a third dimension, the flange must also be measured. While it is convenient to think of the measuring and subsequent machining processes in two dimensions, the method is not so limited. Parts may be manufactured in three dimensions using normal metal-working or other material-working machines to shape and form the parts as desired. Thus, a flange may be added to otherwise flat sheetmetal by designing in the required bend and using a press brake. Other forming processes may also be used, including machining techniques, or molding or forming techniques better suited to non-metallic materials, such as composites, reinforced composites, thermoplastics and thermoset plastic materials.
[0030] It is not necessary that the measuring device measure every feature of the repair part. In the example given, the bulkhead may be secured to the underlying structure by a number of fasteners through holes in the bulkhead. Because of dimensional change over time, these holes must be measured. However, other holes in the bulkhead may not need to be measured. For instance, reinforcing panels, doublers, and other components may be fastened to a main portion of the bulkhead with some fasteners but not to the aircraft by other fasteners. There is thus no reason to measure these particular holes precisely, since they were not subject to movement and may be placed wherever convenience and design rules allow, such as the holes placed in the original design and manufacture. Thus, another aspect of the method is adding additional manufacturing data to the measured data.
[0031] The situation may be as depicted in FIG. 9, in which a bulkhead repair is being planned. Manufacturing and installing the panels depicted in the figure will repair the bulkhead. The largest structure 80 may be smaller than the desired bulkhead because of material, machinery, or manufacturing limitations. Therefore, side panels 81 and 82 augment panel 80 . Several other doublers 83 , 84 , 85 and triplers 86 , 87 , 88 , 89 are also needed for the repair. In order to manufacture the parts, it may have been necessary to measure the periphery of the bulkhead, which periphery will include the edges of parts 80 , 81 , 82 , 83 and 84 in this example. Some of the circular cutouts may be stable and not require measurement, some may require measuring. If the placement of the cutouts is important for some function, then it may be prudent to include them in the measuring portion of the process.
[0032] Holes used by fasteners to secure the bulkhead to the underlying structure should be measured according to the process. Data for holes needed only to secure doublers or reinforcing panels may possibly be imported from the original equipment manufacturer or other source acceptable to any warrantor or regulator of the equipment. These may include the equipment manufacturer or builder, and may include regulatory authorities responsible for regulating the use of the equipment. If a portion or a feature of the structure is such that it did not require custom manufacturing or fitting, and its dimensions are known, it may not be necessary to measure the part before cutting its replacement. In such cases, data for these features may be imported from another source and used instead.
[0033] Note that the method may allow the measured bulkhead shown in FIG. 2 to be fabricated by directly making the detailed parts depicted in FIG. 9. The method will provide for the measuring and digitization of the feature data for the features shown in FIG. 2. If the part is small enough, if material is available, and if a single machine large enough to manufacture the part is available, then further process planning may not be needed. In many instances, however, it is the large size that gives rise to the difficulty of fitting up such a repair part, and a number of pieces will be needed, not merely one piece. In those instances, a process planning step allows for the transformation from the data gathering portion of the method to the manufacture of the parts.
[0034] In process planning, a user converts the measured data into a usable format. The user may also convert the data into several contiguous parts for ease of manufacturing and assembly, rather than a single part. The user may refer to the original equipment manufacturer's design as part of the repair process, for instance, to define parts and split the repairs into a number of parts, as shown in FIG. 9. Process planning may be performed automatically on some parts, but typically is done by process engineers or planners. After splitting a repair structure into a number of discrete pieces, the planner may then use the gathered and digitized data to generate process plans and programs for each part. If more than one manufacturing step is involved, each part may have a number of operations, set-ups, programs and machines for its manufacture.
[0035] Even for a simple part, process planning may be involved in order to speed-up manufacturing and make it more efficient. For instance, if the fastener holes to be drilled are of more than one size, each size may be placed on a different layer in a computer-aided manufacturing (CAM) program, such as AutoCAD® or Mastercam® or CATIA®. AutoCAD® is a product of AutoDesk®, Inc., San Rafael, Calif. Mastercam® is a product of CNC Software, Inc., Tolland Conn. CATIA® is a product of Dassault Systemes, Paris, France, and is represented in the United States by IBM. When the part is manufactured, a machine tool may then drill all holes having the same diameter in a single operation with a single tool before proceeding to another operation. Manufacturers will perform these and other process practices well known to those skilled in manufacturing arts.
[0036] [0036]FIG. 10 depicts a panel 92 being drilled on a CNC router according to information on the dimensions of the panel, the information gathered through the measuring process and other data available to the organization making the repair parts. FIG. 11 depicts a panel 94 being formed on a press brake by a punch 96 and die 98 . Whatever the repair part desired, the process must be governed by process engineering in order to achieve economical and timely repair parts, considering that most production under this method will be limited to a lot size of one. While drilling and forming processes have been depicted, the process is not limited to these, and other precision parts may also be made. Other processes may include, but are not limited to, forming, blanking, routing, tapping, turning, milling, and grinding.
[0037] A user may use a variety of technologies to capture the data from the part requiring repair. Any method suitable for use in a computer-aided design/computer-aided manufacturing (CAD/CAM) environment is acceptable. In one method of practicing the invention, a measuring device from Faro uses SAP software to capture the measuring data in the form of a solid model. Other measuring devices may use software from VDA or other source. It is convenient if the data, in whatever format, may be exported from the measuring device and its memory as an IGES (initial graphics exchange specification) file. In one embodiment, the measured data is imported as an IGES file into a Mastercam® program. A process engineer then programs one or more machines to manufacture the parts automatically. In another embodiment, the measuring device is programmed in AutoCAD® or other program directly suitable for CAM or for which a translator is available. The data may then be manipulated, for instance to check its integrity and its reasonableness, as well as to add other data as mentioned above. Any perceived errors may be corrected at this stage as well. Other data or features desired may be added here as well, whether by a programmer or designer, or by importing another data file.
[0038] The file or files may then be prepared for computer-aided manufacturing. The data may be split into separate parts, as shown for instance, in FIG. 9, deleting in a given file all sections not required for a given part. In the case of sheetmetal or other flat parts, it may also be convenient to nest the parts in order to conserve material. A program called TruNest™ has been found very useful for process planning in this step. TruNEST™ is a product of Magestic Systems, Inc., Old Tappan, N.J. Process engineering for flat or sheetmetal parts is fairly straightforward. Process planning for other parts calls for the normal process engineering functions. Once the operations have been broken down into setups and stations, machining or manufacturing may proceed automatically in a normal computer-aided manufacturing, NC or CNC environment. Once a file has been prepared for CAM, the file may be exported to an NC (numerical control) or CNC (computer numerical control) machine for manufacture of the part.
[0039] While this invention has been shown and described in connection with the preferred embodiments, it is apparent that certain changes and modifications, in addition to those mentioned above, may be made from the basic features of this invention. For example, aircraft parts have been featured, but the method is not limited to aircraft parts. The method may apply to any structure having parts or components in need of repair. These may include, but are not limited to, large machines or structures, for instance ships, buildings, locomotives, machinery, draglines, process-equipment vessels or reactors, large machine tools, bridges and dams. While measuring machines from Faro Technologies have been mentioned, any suitable digital measuring machine may be suitable, including those made by Boice, Brown & Sharp, Mitotoyo, Numerex, Sheffield, Zeiss and others.
[0040] Because of the importance of not causing damage to structures such as aircraft, it is prudent to use an operator to hand-guide a CMM axis as it approaches a measurement point; however, the invention will work with a conventional-coded CMM given multiple points to approach and inspect. The invention has been described in terms of a structure's strains and departures from its as-manufactured state; however, original manufacturing and inspection data may be used as a starting point for each feature that a user wishes to measure in using the method of the present invention. While the method is more advantageously used in large structures and large parts needing repair in those structures, it may be used to repair small structures and small portions as well, for instance, when such parts are out-of-stock or have very high prices. Accordingly, it is the intention of the applicants to protect all variations and modifications within the valid scope of the present invention. It is intended that the invention be defined by the following claims, including all equivalents. | A method for repairing structures uses an accurate measurement of the part to be repaired and the structure into which it fits. The method allows for a digital measurement of features of the part and the structure, and eliminates tedious and inaccurate hand-measurement methods previously used. The method is primarily applicable to one-of a-kind parts requiring exact measurements, because of the unique shape that a part may assume when it is subject to stress and strain over time and many cycles of use. | 1 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
A lawn sprinkler assembly and more particularly a wheeled support lawn sprinkler assembly for easily moving a lawn sprinkler around a large or small size yard which assembly contains a shut off valve, a collapsible wheel assembly and a collapsible support rod.
2. Description of Related Art
Proper irrigation of a lawn, garden or turf is a time consuming task requiring the constant movement of hoses and attached sprinklers. Each time the sprinkler is to be moved, the water line must be shut off at the shut off location, usually the house, the hose moved and then the water turned back on. This identical process may be undertaken several times a day depending upon the size of the area to be watered. While home owners desire a green lawn, the constant need to turn on and off the water supply and drag the hoses and sprinklers can become overwhelming and can, in certain circumstances, result in physical injury.
Water sprinkler systems of various designs, structure, configurations and materials of construction have been disclosed in the prior art. For example, U.S. Pat. No. 1,959,886 to Wadsworth discloses a portable sprinkler support that has a tripod supporting ring having non-extendable bamboo legs for use in watering and spraying of fruit trees. The water is passed through a central non-extendable pipe and a sprinkler head. This prior art patent does not disclose the particular structure and design of the water sprinkler system of the present invention.
U.S. Pat. No. 2,694,600 to Richey discloses a lawn sprinkler stand having a C-shaped configuration base supported by a tripod collar having braces that are non-extendable and connected to the C-shaped base. The water is passed through a central extendable pipe and a sprinkler head. This prior art patent does not disclose the particular structure and design of the water sprinkler system of the present invention.
U.S. Pat. No. 4,824,020 to Harward discloses a sprinkler stand having a central support hub with a plurality of at least five non-extendable legs, and the water is passed through a short central pipe and a sprinkler head. This prior art patent does not disclose the particular structure and design of the water sprinkler system of the present invention.
U.S. Pat. No. 5,439,176 to Bussiere discloses a lawn-garden sprinkler having a tripod support structure. The tripod support structure includes a spindle axis having non-extendable support rods which radiate outwardly from the central axis being connected to tie rods. The tie rods are welded to the support rods to provide a rigid tripod construction resistant to fracture or bending forces. The water passes through a short angled pipe and a sprinkler head. This prior art patent does not disclose the particular structure and design of the water sprinkler system of the present invention.
None of the prior art water sprinkler systems disclose the structure, configuration and functionality of the present invention.
Accordingly, it is the primary object of the present invention to provide a sprinkler assembly which can be easily moved from place to place, can be easily and conveniently stored, and is inexpensive and non-corrosive.
A further objective of this invention is to provide a sprinkler assembly which is easy to use and inexpensive for the consuming public.
It is a further object of the present invention to provide a sprinkler assembly of simple design, durability and sturdiness.
It is the further object of the present invention to provide a sprinkler assembly containing a valve for stopping the water from continuing to the sprinkler, thereby eliminating the need for the water to be turned off at its source each time the sprinkler assembly is to be moved.
It is the further object of the present invention to allow a variety of sprinkler heads to be attached to the sprinkler assembly to properly accommodate the area to be watered.
It is the further object of the present invention to provide a sprinkler assembly that is of simple structural configuration for easy setup for water spraying of lawns, gardens, arenas, flowers, shrubs, orchards, and trees.
It is a further object of the present invention to provide a sprinkler assembly that is foldable into a portable configuration for easy carrying and storage by the user without removing any bolts or nuts.
SUMMARY OF THE INVENTION
A lawn sprinkler assembly according to the present invention includes a single length of suitable piping having two open ends to which a shut-off valve and a sprinkler are attached. To easily maneuver the sprinkler assembly, the sprinkler assembly includes a wheel assembly which wheel assembly can be collapsed for easy storage of the sprinkler assembly.
The sprinkler assembly also contains a support assembly which allows the sprinkler assembly to be maintained above ground level so as to avoid the need for the user to bend over and lift the piping when moving the sprinkler assembly. The rod assembly can also be easily collapsed for easy storage of the sprinkler assembly.
These, and other, aspects and objects of the present invention will be better appreciated and understood when considered in conjunction with the following description and the accompanying drawings. It should be understood, however, that the following description, while indicating preferred embodiments of the present invention, is given by way of illustration and not of limitation. Many changes and modifications may be made within the scope of the present invention without departing from the spirit thereof, and the invention includes all such modifications.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side perspective view of the sprinkler assembly in accordance with the preferred embodiments of the present invention.
FIG. 2 is a side perspective view of the sprinkler assembly with an attached sprinkler head in accordance with the preferred embodiments of the present invention.
FIG. 3 is a side perspective view of the sprinkler assembly in a folded position in accordance with the preferred embodiments of the present invention.
FIG. 4 is a side perspective view of the sprinkler assembly's shut-off valve and supply hose in accordance with the preferred embodiments of the present invention.
FIG. 5 is a side perspective view of the plate and tubular receiver of the lock assembly in accordance with the preferred embodiments of the present invention.
FIG. 6 is a front perspective view of the plate of the lock assembly in accordance with the preferred embodiments of the present invention.
FIG. 7 is a side perspective view of the clamp, plate and tubular receiver of the lock assembly in accordance with the preferred embodiments of the present invention.
FIG. 8 is a side perspective view of the square tubing and the lock assembly's spring and tubular insert in accordance with the preferred embodiments of the present invention.
FIG. 9 is a side perspective view of the lock assembly in accordance with the preferred embodiments of the present invention.
FIG. 10 is a side perspective view of the lock assembly in accordance with the preferred embodiments of the present invention.
FIG. 11 is a side perspective view of the lock assembly with the square tubing in a vertical position in accordance with the preferred embodiments of the present invention.
FIG. 12 is a side perspective view of the lock assembly with the square tubing in a horizontal position in accordance with the preferred embodiments of the present invention.
FIG. 13 is a front perspective view of the wheel assembly in accordance with the preferred embodiments of the present invention.
FIG. 14 is a front perspective view of a wheel and wheel arm in accordance with the preferred embodiments of the present invention.
FIG. 15 is a front perspective view of the wheel assembly with the attached tubular insert in accordance with the preferred embodiments of the present invention.
FIG. 16 is a front perspective view of the support assembly in accordance with the preferred embodiments of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention and the various features and advantageous details thereof are explained more fully with reference to the non-limiting embodiments described in the following description.
FIGS. 1 through 16 show a device of the present invention which can be used for easily watering a lawn, garden, riding arena, flower bed and the like. The sprinkler assembly 20 is comprised of a section of suitable piping 22 , a wheel assembly, a support assembly 56 and a pair of lock assemblies 68 .
Referring to FIGS. 1 , 2 and 3 , the sprinkler assembly 20 consists of a single length of suitable piping 22 having a first open end 24 and a second open end 26 . Adjacent to the first open end 24 is a shut-off valve 28 which allows the user to turn off the water flowing into the piping 22 . The first open end 24 of the piping 22 is female threaded. The male end of a supply hose 30 is removable attached to the female threads of the first open end 24 of the piping 22 .
The second open end 26 of the piping 22 is a threaded male end. In the preferred embodiment, the female end of a sprinkler 32 is removably attached to the male threaded second open end 26 . In an alternative embodiment, the first female end of a ninety-degree elbow fitting 34 is removably attached to the male threaded second open end 26 . The male threaded end of a sprinkler head 36 is removably attached to the second female end of the ninety-degree elbow fitting 34 .
In an alternative embodiment of the present invention, multiple sprinklers can be utilized by attaching the female end of a “T” connector (not shown) to the male threaded second open end 26 of the piping 22 . The first ends of extension pipes (not shown) can then be removably attached to the open ends of the “T” connector with sprinklers attached to the second ends of the extension pipes.
Referring to FIGS. 13 , 14 and 15 , to easily move the sprinkler assembly 20 from point to point, a wheel assembly 38 is incorporated into the preferred embodiment. The wheel assembly 38 is comprised of a pair of wheels 40 , a first wheel arm 42 , a second wheel arm 44 , and a wheel assembly extension tube 46 . Each wheel arm 42 , 44 has a first arm end 48 and a second arm end 50 with the first arm ends 48 fixedly attached to the second end 47 b of the extension tube 46 . A portion of each second arm end 50 is bent 52 at an angle to the remaining portion of the second arm end 50 . Each of the bent portions 52 of the arms 42 , 44 is so bent that when each of the arms 42 , 44 is fastened to the extension tube 46 , the bent portions of each of the arms 42 , 44 are coaxial, and form axles 54 . Each wheel 40 is held rotatably secured to the axle 54 by means of a suitable quick-acting lock mechanism (not shown) which is easily released when the wheels 40 are to be removed.
To maintain the sprinkler assembly 20 in a horizontal position so the user can attach or detach the supply hose 30 , adjust the shut-off valve 28 or move the sprinkler assembly 20 without having to bend over, a support assembly 56 is provided. Referring to FIG. 16 , the support assembly 56 is comprised of a support assembly extension tube 58 having a first end 60 and a second end 62 . Fixedly attached to the extension tube's 58 second end 62 is an “O” shaped hook 64 . Attached to the hook 64 is a spike 66 which spike 66 can be pushed into the ground surface to maintain the sprinkler assembly 20 in its desired position.
Both the wheel assembly 38 and the support assembly 56 are rotatably maintained on the sprinkler pipe 22 through a pair of lock assemblies 68 . Referring to FIGS. 5 through 12 , each lock assembly 68 is comprised of a plate 70 , a tubular receiver 72 , a clamp 74 , a tubular insert 76 , a spring 78 , and a pin 80 . The plate 70 is rectangular shaped having a front side 82 , a back side 84 , a top end 86 and a bottom end 88 . Below the top end 86 are a pair of vertically spaced small diameter cylindrical openings 90 . Above the bottom end 88 is a large diameter cylindrical opening 92 .
The first open end 94 of the tubular receiver 72 is fixedly attached over the large diameter cylindrical opening 92 so that the second open end 96 of the tubular receiver 72 is at a right angle to the plate 70 . The second open end 96 of the tubular receiver 72 contains a plurality of notches 98 .
The clamp 74 , which is mountable to the plate 70 , is preferably “U” shaped which defines a diameter substantially equal to or greater than the diameter of the pipe 22 to be retained therein. In the preferred embodiment of the present invention, the clamp 74 has outwardly extending flanges 100 attached to the ends 102 of the generally horizontal leg sections 104 . The flanges 100 contain openings 106 which openings 106 are aligned with the small diameter openings 90 of the plate 70 . A bolt 108 is interested into the aligned openings 90 , 106 and maintained in place with a nut 110 so the clamp 74 and plate 70 are removably attached.
Referring to FIGS. 8 , 15 , 16 , fixedly attached near the first ends 47 a, 62 of the extension tubes 46 , 58 is the first end 112 of a tubular insert 76 . The tubular insert 76 is at a right angle to the extension tubes 46 , 58 . The diameter of the tubular insert 76 is slightly less than the diameter of the tubular receiver 72 so as to allow the tubular insert 76 to be rotatable within the tubular receiver 72 . Near the second end 114 of the tubular insert 76 is a cylindrical opening 116 . Maintained on the tubular insert 76 is a spring 78 .
The tubular insert 76 is rotatably inserted into the tubular receiver 72 with the plate 70 and extension tube 46 , 58 pressed together so that the second end 114 of the tubular insert 72 extends beyond the second end 96 of the tubular receiver 72 and a pin 80 inserted into the cylindrical opening 116 of the tubular insert 76 . Releasing the plate 70 and extension tube 46 , 58 causes the spring 78 to pull the extension tube 46 , 58 away from the plate 70 . The pin 80 , removably attached to the tubular insert 76 , is pulled into the notches 98 of the tubular receiver 72 thereby resulting in the tubular insert 76 being maintained within the tubular receiver 72 .
To collapse or otherwise adjust the wheel assembly 38 and/or support assembly 56 , a user need simply press the extension tube 46 , 58 and plate 70 together resulting in the pin 80 being dislodged from the notches 98 . With the pin 80 dislodged, the tubular insert 76 can be freely rotated within the tubular receiver 72 . Once the desired position of the wheel assembly 38 and/or support assembly 56 has been achieved, the user can release the extension tube 46 , 58 and plate 70 causing the pin 80 to become lodged within the notches 98 corresponding with the position desired.
Although the best mode contemplated by the inventor of carrying out the present invention is disclosed above, practice of the present invention is not limited thereto. It will be manifest that various additions, modifications and rearrangements of the features of the present invention may be made without deviating from the spirit and scope of the underlying inventive concept.
The individual components mentioned herein need not be fabricated from the disclosed materials, but could be fabricated from virtually any suitable and strong materials.
Moreover, the individual components need not be formed in the disclosed shapes, or assembled in the disclosed configuration, but could be provided in virtually any shape, and assembled in virtually any suitable configuration. It is intended that the appended claims cover all such additions, modifications and rearrangements. | A wheeled lawn sprinkler assembly for easily moving a lawn sprinkler around a large or small size yard which assembly contains a shut off valve, a collapsible wheel assembly and a collapsible support assembly. | 0 |
This application is a division of Ser. No. 08/848,781 filed May 1, 1997 now U.S. Pat. No. 5,902,306.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a surgical instrument for driving elongated pins or wires. In particular, the invention relates to a pin or wire driver having a collet mechanism which permits the pin or wire to be selectively released and engaged in order to be repositioned. The mechanism also permits automatic sizing of the collet to accept a range of pin/wire diameters. More particularly, the invention relates to a pin or wire driver collet adjustment mechanism suitable for one-handed operation.
2. Description of the Prior Art
Powered surgical instruments for driving elongated pins or wires are well known. While pins usually have larger diameters than wires, for purposes of this description, the terms "pins" and "wires" will be considered interchangeable. For simplicity, the term wire driver will be used to mean a driver for driving pins as well as wires or other similar, wire-like elongated devices (i.e. relatively rigid shafts which may or may not have pointed or drill tips and are usually, but not necessarily, made of metal such as stainless steel, nitinol, etc.) . Such instruments generally comprise a handpiece adapted to drive a cannulated drive shaft through which a wire may be passed. Since the wire to be driven may be relatively long, the drive shaft extends entirely through the handpiece from a proximal end to a distal end and is provided with a collet/chuck mechanism in order to selectively secure the wire to the drive shaft. The instrument is used to turn the drive shaft which, consequently, turns the wire in order to advance the wire extending from the distal end of the drive shaft into a bone or other structure at a surgical work site. Depending upon the desired penetration depth and other factors, the length of wire extending from the distal end of the drive shaft may need to be adjusted in order to optimize control of the wire. The wire's extended length is usually relatively short as the wire is first driven into the surgical work site and then, if additional penetration is desired, the grip on the wire is somehow overcome or released so the wire may be repositioned within the drive shaft and driven further into the surgical work site. Often, the collet mechanism is similar to a one-way clutch which permits the wire to be pulled out of the handpiece distally, but does not permit it to be pushed proximally. It will be noted that once the wire is sufficiently embedded at the surgical work site in a bone, for example, the distal end of the wire will be held in place by the bone. That is, in such a case there is no need for a surgeon to grasp the wire because the collet mechanism allows the wire to "slip" when the handpiece moves proximally along the wire (and the wire moves distally). The surgeon simply needs to move the handpiece relative to the wire until the desired length of wire extends from the drive shaft.
Some prior art wire drivers are provided with collet mechanisms which frictionally engage the wire at all times to a certain degree. This is necessary as a practical matter so that the wire does not simply fall out of the wire driver as the latter is manipulated during use. Other prior art wire drivers enable the wire to slide more freely. One example of such a prior art wire driver is described in U.S. Pat. No. 4,736,742 (Alexson et al.) which shows a wire driver attachment releasably attached to a gas operated handpiece having a pair of parallel output drive shafts, one of which is cannulated. The handpiece has a pistol-grip and a trigger for activating its drive shafts. The wire driver attachment fits on the handpiece in such a way as to align the cannulated output shaft with the wire being driven. A pivotable, spring-loaded lever is situated on the wire driver attachment and is movable between a release position, spaced away from the pistol-grip handle, and an engage position adjacent the handle. The action of the lever controls a cam surface in the attachment by moving it to selectively release or engage a plurality of locking balls circumferentially arranged around the wire being driven. The locking balls and associated cam surfaces are components of a threaded, cylindrical chuck which is adjustable by a user, using a second hand, so the wire can be frictionally held by the locking balls. However, this adjustment is usually made in practice just to size the collet for the wire. That is, in actual use the locking balls are adjusted close to but not simultaneously contacting the wire and cam surface. The wire may then be normally fully released so that it could fall out of the driver or the mechanism may be adjusted so the wire can be slid longitudinally through the chuck with the lever in the release position (i.e. its normally biased position). In either case, the wire would be tightly engaged by the locking balls when the lever is in the engage position. The handpiece is activated by a user pulling an activating trigger while moving the lever to the engage position. When pressure is removed from the lever, it returns to its release (i.e. lightly gripping or sliding) position in which the device allows longitudinal movement of the wire relative to the chuck. In any case, the wire driver shown in this patent requires a two-handed operation for any adjustment of the cylindrical part which sizes the mechanism to match the wire then in use.
Another known wire driver assembly utilizes a collet mechanism based on a plurality of gripper discs circumferentially arranged about a wire to be driven. Such a device is available from Zimmer, Inc., Warsaw, Ind. (an affiliate of the assignee of this invention) in the form of a lever-less pin driver assembly more particularly described below by reference to FIG. 6.
The aforementioned devices as well as other conventional wire drivers are designed and adjusted to hold wires in position so they will not move or fall out of the collet under their own weight. As mentioned, this is necessary as a practical matter to prevent the wires from falling out of the handpiece. However, this produces a disadvantage in that once the wire has been initially inserted into the driver, minor adjustments of the wire position in the collet are not easily achievable. The surgeon must either use his/her other hand or the assistance of another person in order to achieve the precise wire position desired. Since the surgeon's other hand may already be occupied, this is an obvious limitation which may adversely affect the efficiency of the surgical procedure.
It has been found that it would be desirable to enable a surgeon to simply rest the distal tip of the wire against a sterile surface (such as a surgical drape, etc.) and, with the hand holding the driver, release the wire so it can fall under its own weight. This would enable the surgeon to move the driver up or down the wire without the assistance of another person and without having to grasp the wire, while also having the driver normally maintain a light grip on the wire preventing it from falling out. The same mechanism enables the wire driver to automatically adjust its collet size to accept a wide range of wire diameters.
Accordingly, it is an object of this invention to produce a wire driver collet mechanism which enables the wire to be selectively repositioned or engaged.
It is a further object of this invention to produce a wire driver collet mechanism which enables the wire to be selectively repositioned under its own weight.
It is another object of this invention to produce a wire driver collet mechanism, for a wire driver handpiece, in which the wire may be selectively repositioned easily with a one-handed operation utilizing the same hand which holds the wire driver handpiece. That is, it is also an object of this invention to produce a wire driver which enables a user to selectively reposition the wire driver on the wire while using only one hand to hold the driver and control the collet holding the wire.
It is another object of this invention to enable this to be done with a lever-operated wire driver attachment since that is a structure commonly used in similar devices.
It is an additional object of this invention to produce a wire driver collet mechanism which automatically adjusts to accept a wide range of wire diameters.
SUMMARY OF THE INVENTION
These and other objects of this invention are achieved by the preferred embodiment disclosed herein which is a surgical instrument comprising a handpiece and a wire driver attachment for receiving and driving a wire-like member. The handpiece has a handle for being held by a hand and the wire driver attachment has a gripper means for selectively securing the wire-like member to a drive shaft in the handpiece. The gripper means is movable between a release position in which the wire-like member is movable under its own weight, and an engage position in which the wire-like member is frictionally retained sufficiently to be driven. An adjustment means is connected to the gripper means for selectively moving it between the enable and the release positions, the adjustment means being operable by the hand holding the handpiece. Once the wire is loaded into the driver, all further desired adjustments of exposed wire lengths are accomplished with the same hand which holds the handpiece. In the preferred embodiment the adjustment is done by a lever actuator situated in front of a pistol-grip handle, the lever being pivotable relative to the handle so it can be moved by the fingers of the hand holding the handpiece.
The invention also resides in the method of adjusting a wire-like member within a wire driver such as that described above. The method comprises the steps of providing a surgical wire driver, holding it in one hand, and placing a surgical wire within the cannulated drive shaft. The method further comprises the steps of providing a collet means for securing the wire to the drive shaft and providing an actuating member for selectively moving the collet means between a release and engage position. The actuating member is moved to the release position by a portion of the same hand in which the wire driver is held thus allowing the wire to move by its own weight relative to the driver until it reaches a selected position. The actuating member is then released so that it returns to its normally biased engage position.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side elevational schematic view partly in cross-section of a wire driver constructed in accordance with the principles of this invention.
FIG. 2 shows the wire driver attachment of FIG. 1 in the release position.
FIG. 3 is a sectional view of FIG. 2 taken along the line 3--3.
FIG. 4 is a view of FIG. 2 showing the wire driver attachment in an engage position.
FIG. 5 is a sectional view of FIG. 4 taken along the line 5--5.
FIG. 6 is a view of a prior art pin driver assembly showing the use of the gripper discs used in the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
As shown in FIG. 1, wire driver 10 comprises a handpiece 12 having a pistol-grip handle 14 and a top, transverse body portion 16. Body portion 16 has a distal end 18 and a proximal end 20 and it and handpiece 12 contain a conventional motor and cannulated drive shaft (not shown) for driving a wire inserted through bore 22 extending entirely through body portion 16 from proximal end 18 to distal end 20. The handpiece is also provided with a trigger 24 for activating the drive mechanism which may be either pneumatic or electric and forms no part of this invention.
Wire driver attachment 30 is secured, preferably releasably, (by means not shown) to distal end 18 of the top body portion 16 so as to engage its rotatable cannulated drive shaft 32 with the motor drive shaft (not shown) in handpiece 10. Attachment 30 comprises a collet mechanism 34 which selectively engages and releases wire 38 via a pivotable control lever 36, the operation of which will be best understood by reference to FIGS. 2 through 5. Drive shaft 32 has a hexagonally profiled outer surface at its proximal end 40 for engagement within a complementarily shaped motor drive shaft (not shown) and a cylindrical outer surface at its distal end 42 rotatably situated within bearings 44, 46 and 48. Collet mechanism 34 circumferentially surrounds wire 38 at the distal end of the wire driver attachment and comprises a plurality of circumferentially arranged gripper discs 50 retained within a gripper housing 52 at the distal end 54 of drive shaft 32. As will be understood below, all of the gripper discs operate in conjunction with a cylindrical cam assembly 60 which is longitudinally positioned to either place the gripper discs in an engage position or allow them to move into a release position.
Gripper discs such as those shown are conventional structures which are not themselves part of the invention. Nevertheless, some brief description of the operation of the gripper discs is helpful to understand the invention. In the preferred embodiment, three gripper discs 50 are positioned equiangularly about the axis 63 so that the planar bodies of the discs are rotatable within circumferentially spaced axial planes P1, P2 and P3, as best seen in FIG. 3. Each gripper disc 50 has an annular groove 62 designed to enhance the frictional engagement between the disc and an associated wire 38 which is to be gripped. Each disc is situated in a radial slot 68 formed in the exterior cylindrical surface of housing 52 at the distal end of drive shaft 32 and each slot has a transverse width sufficient to accommodate the cylindrical body of its associated disc. Each slot 68 is further provided with a pair of opposed slots 66 for receiving the ends of disc axle members 64 thereby enabling each gripper disc to rotate about its axis and to slide under its own weight radially inwardly and outwardly along this axis slot.
As shown in FIG. 6, gripper discs such as those described herein have been used in prior art wire driver assemblies although their use is considerably enhanced by the subject invention. A prior art wire driver assembly 200, in the form of an attachment for being secured to a handpiece similar to handpiece 10, comprises a throughbore 202 for receiving a wire to be driven. The assembly 200 is secured to an adapter 203 which may be one of several configurations adapted in order to fit the assembly to a particular handpiece (not shown). The adapter is threaded into the body of assembly 200 and secured by a set screw 205. A nose member 204 is secured to the distal end of a cannulated drive shaft 206 which carries at its mid-section a gripper housing 208 having a plurality of circumferentially arranged gripper discs 210 (only one of which is shown). A cylindrical cam assembly 212 is interposed between nose member 204 and drive shaft 206 so as to provide a conically tapered cam surface 214 adjacent the gripper discs. Spring 216 is retained between ring 218/washer 220 at its distal end and gripper housing 208 at its proximal end. The spring biases drive shaft 206 and gripper discs 210 proximally, thus urging the discs against cam surface 214 (the gripper discs would otherwise be loosely movable radially inwardly and outwardly as described above). Cylindrical cam assembly 212 is movable against the force of spring 216 between an engage position, as shown in FIG. 6, and a release position (not shown) in which gripper housing 208 is displaced to the left of the position shown in FIG. 6--out of engagement with cam surface 214. Such longitudinal movement of the cam assembly is controlled by nose member 204 and adjustment ring 222 threadably engaged with locking sleeve 224 concentrically situated about the proximal end of cylindrical cam assembly 212. Drive shaft 206 is restricted to be only longitudinally movable relative to cylindrical cam assembly 212 by a conventional pin and slot arrangement: diametrically opposed pins 230, 232 are attached to the drive shaft and received within a corresponding pair of longitudinal slots 234, 236, respectively, extending through the surface of cam assembly 212 to prevent relative rotation. A pair of transverse slots 238 (only one of which is shown) at the distal end of the longitudinal slots enables the nose member and drive shaft to be turned into an open and locked position to keep tension off the gripper discs to enable loading of a wire. Locking sleeve 224 is threadably adjustable between the position shown in FIG. 6, in which the sleeve abuts a proximally facing shoulder on the cam assembly and thereby permits the attachment to be placed into an open/load configuration in which the pins 230, 232 engage slots 238 to keep the device open to enable wire loading, and a locked position (not shown) in which the sleeve is spaced proximally from the shoulder as adjustment ring 222 is turned. The position of sleeve 224 is continuously variable between these two extremes and it is only at the locked position that the sleeve abuts pins 230, 232 and prevents any motion of the drive shaft relative to the cam assembly. In all but the open/load and locked positions a wire inserted through bore 202 will be gripped solely by spring tension urging housing 208 in a proximal direction against cam surface 214. By virtue of the relatively small angle of inclination of conical cam surface 214, the wire being driven will be tightly gripped as it is pushed distally into a bone and then, once sufficiently embedded into the bone to be tightly held by the bone, the wire driver may be pulled back, enabling the wire to roll along the gripper discs to a new position. In the open/load position the spring will be effectively disengaged from the discs and they will be free to move under their own weight, and in the locked position the threaded sleeve 224 will urge the cam surface 214 against the discs and add to the spring force, thus effectively limiting the ability of the discs to roll along the wire.
Returning now to FIG. 2, cylindrical cam assembly 60 comprises a conical cam surface 70 at the distal end of a cam body 71, a tubular body 72 interposed between the cylindrical drive shaft portion 42 and bearings 46 and 48, and a slidable, cylindrical block assembly 74 which actually receives bearings 46 and 48 at its opposing ends. Block assembly 74 is rotatably secured to cam assembly 60 by being retained between shoulder 75 on the exterior surface of the cam body 71 and a retaining ring 77. Block assembly 74 is provided with a central transverse aperture 76 surrounding tubular body 72 and within which is situated the proximal end 78 of lever 36. The lever is pivotably attached at pivot point 80 to the housing of wire driver attachment 30 so that movement of the distal portion 82 of lever 36 about pivot 80 will cause the proximal end 78 to move block assembly 74. Spring 84 is provided between bushings or end caps 86 and 88 and biases block assembly 74 in the distal direction. Thus, the position of the components shown in FIG. 4 represents the normal, i.e. engage position of the device in which the spring tension ultimately acts on gripper discs 50 to engage a wire. This spring tension also causes lever 36 to be pivoted counterclockwise about pivot 80. As shown in FIG. 2, lever 36 may be pushed in a direction 90 by a user. Such distal motion of lever 36--which may be done by the fingers of the same hand gripping handle 14--causes cam assembly 60 to move proximally against the spring tension into an open/load position, thereby allowing gripper discs 50 to be released from their engagement with the radially inner portion of cam surface 70. This is diagrammatically shown in FIG. 3 by representing the gripper discs as being at their radially outermost position, however, it will be understood that the gripper discs are not spring loaded so as to automatically cause all of them to move radially outwardly in all directions simultaneously. They will, nevertheless, individually move radially outwardly under the influence of gravity if the wire driver happens to be oriented to enable this. In any event, the frictional engagement between cam surface 70 and those discs that do not fall away will be reduced to such a level that the wire 38 may fall under its own weight through bore 22 in either the proximal or distal direction, assuming of course that the driver is held so as to orient the wire vertically.
Once the wire is positioned as desired, one simply needs to remove the outwardly directed force on the lever as shown in FIG. 4. This will enable the spring to return to its normally "closed" position in which the gripper discs move into engagement with the wire. In this position the wire is automatically gripped to keep it from falling out. An additional force 92 may then be exerted on lever 36 if the user simply grips lever 36 simultaneously with handle 14. This extra force enhances the grip on the wire by causing the upper end 78 of lever 36 to urge cam assembly 60 distally thereby bringing gripper discs 50 into progressively tighter engagement with cam surface 70 until the gripper discs tightly engage wire 38.
Spring 84 will ensure that the cam surface 70 is urged distally with sufficient force to properly grip the wire sizes for which the particular attachment is designed. While in the preferred embodiment the acceptable wire sizes range from 0.079 inches (2 mm) in diameter as shown in FIGS. 4 and 5 to 0.126 inches (3.2 mm) in diameter as shown in FIGS. 2 and 3, it will be understood that the invention is adaptable to all wire diameters by simply making dimensional changes accordingly.
While the preferred embodiment is described with gripper discs 50, it will be understood that locking balls or other rolling elements could also be adapted for use instead of the discs. In each case, the operation of the device between a normally closed (locked) position and an open/load position is under the control of the hand holding the wire driver and no further adjustment is necessary, regardless of wire size.
Similarly, while shown as a lever actuated, pistol-grip type of handpiece, the principles of this invention may be adapted to a variety of other configurations such as, for example, to a pencil-grip type of handpiece utilizing a slide actuated mechanism instead of a lever.
It will be understood by those skilled in the art that numerous improvements and modifications may be made to the preferred embodiment of the invention disclosed herein without departing from the spirit and scope thereof. | A wire driver collet mechanism for selectively enabling the repositioning of a wire within a wire driver. The adjustable collet mechanism enables the wire to be repositioned under its own weight so that a user is not required to grasp the wire, thereby enabling one-handed operation of the wire driver. A method of adjusting a wire within a wire driver utilizes the steps of positioning the tip of a wire against a surface and allowing the wire to move under its own weight while moving the wire driver to position the wire as desired. The release of the wire is under the control of the hand holding the wire driver. | 0 |
FIELD OF THE INVENTION
The present invention generally relates to a method of tightening a bolt or nut with a predetermined maximum torque by the use of a nut runner.
PRIOR ART
In tightening a bolt by the use of a nut runner, overtightening results if the speed of the runner is set to zero when the torque has reached a predetermined value. This is due to the inertia of the motor and to time delay before the speed command reaches the motor.
In order to prevent the excess torque from being applied to the bolt, the speed of the motor should be as close to zero as possible just before the torque applied to the bolt reaches a target value. However, decreased speeds result in increased time required for tightening the bolt and therefore decreasing speed is not practical. Setting the speed close to zero can cause the motor to stop before the torque reaches the target value if the friction is relatively large.
Conventionally, taking the past data and experiences into account, the programmer writes a control program that controllably drives the nut runner stepwise.
Writing a control program requires considerable experience and skill. Most of the users cannot write such a program and an experienced programmer must spend considerable amount of time in writing the control program.
SUMMARY OF THE INVENTION
The present invention is made in view of the aforementioned problems. An object of the invention is to provide a method of tightening a bolt in an optimum time length. Such method does not require an additional program for controlling speed once optimum internal parameters have been determined through several learning cycles.
In the present invention, a target torque is first preset and the nut runner undergoes several learning cycles so that the nut runner automatically determines such internal parameters so as to stop the motor immediately after the target torque is reached, thereby requiring a minimum amount of time for tightening the bolt.
BRIEF DESCRIPTION OF THE INVENTION
Features and other objects of the invention will become more apparent from the description of the preferred embodiments with reference to the accompanying drawings in which:
FIG. 1 is a block diagram of a constant torque bolt-tightening apparatus of the invention;
FIG. 2 is a flowchart showing the operation of the apparatus in FIG. 1;
FIG. 3 shows sample curves of torque T versus rotational speed S;
FIG. 4A shows Curve P8 of FIG. 3 and FIG. 4B shows Curve P2 of FIG. 3;
FIG. 5 shows a torque/speed table produced in accordance with Curve P(s) shown in FIG. 3; and
FIG. 6 illustrates the changes in torque, showing loss in torque after the target torque is reached.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The principle of an apparatus for tightening a bolt with an optimum time length according to the present invention will be described in detail. Kinetic energy of a rotating body is generally given by ##EQU1## where F is an input (target speed), I is a moment of inertia, D is a decaying constant, x is an angular velocity, and t is time.
Equation (1) implies that after the target speed F is changed stepwise, the operating condition of the nut runner is determined by the variables I, D and x, x being an angular velocity immediately after the target speed F is changed. The torque is proportional to the integration of x with respect to time after the nut runner has reached the work to be fastened by the bolt, i.e., after torque is generated.
If the nut runner is operated so that the nut runner runs slowly until the bolt head reaches the work and input speed F is set infinitely close to Dx after the work is reached, then the torque applied to the work slowly approaches the target torque. If the input speed F is set to zero when the target torque is reached, no overshoot results but there will be a very long time before the tightening is completed. In contrast, if the input speed F is set to a large value so that the target torque is reached in the input speed F is set to zero as soon as the target torque is reached, then the nut runner operates according to Equation 2; ##EQU2## with an overshoot given by Equation 3,
∫ωd t (3)
the overshoot existing till x=0.
FIG. 3 shows sample curves of torque T versus rotational speed S, rotational speed S being plotted in the vertical axis and torque T in the coordinate. It is assumed that the rotational speed S is a maximum value when the torque is zero, and the input speed F is set to zero when torque reaches the target torque. Operating the motor in accordance with Curve 8 allows tightening of the nut at a minimum period of time. If the motor fails to follow the Curve P8, then there will be an overshoot.
An embodiment of the present invention will now be described with reference to FIGS. 1 and 2. FIG. 1 is a block diagram of a constant torque bolt-tightening apparatus and FIG. 2 is a flowchart showing the operation of the apparatus. Reference numeral 1 denotes a CPU. A selector switch 2 is used to select one of the curves in FIG. 3 along which the bolt-tightening apparatus undergoes learning cycles. A memory 3 stores the table shown in FIG. 5 therein which shows the normalized values of the rotational speed and torque in FIG. 3. A torque sensor 5 is incorporated in a nut runner 4. Reference numeral 6 denotes an alarm.
At step S1, the switch 2 is operated to set an initial value of the rotational speed S based on the characteristics of the nut runner 4, target torque, and tolerant error E. At step S2, a plurality of curves are produced on the basis of the rotational speed S, target torque, and tolerable error E. At step S2A, Curve P(s) is arbitrarily selected, P(s) being in the relation of Pmin≦P(s)≦Pmax and s being 1, 2, 3, . . . , 8. Curve P(s) may be a curve used in the past. The CPU 1 reads values of T(0) and S(0) for j=0 from Curve P(s) and the value of target torque T(n) for j=n.
FIG. 3 shows curves representing relationships between speed and torque for different parameters, thereby, representing a required speed for a given torque.
FIG. 4A shows Curve P8 of FIG. 3 and FIG. 4B shows Curve P2, the curves P2 and P8 being shown in semi-log scale. Each curve represents a value S(j) of rotational speed S corresponding to a given value T(j) of torque T, where j=1, 2, 3, . . . , n. A larger value of n enables more precise control.
At step S3, a torque/speed table as shown in FIG. 5 is produced in accordance with Curve P(s) shown in FIG. 3, and proceeds to step S4 where the tightening operation is started.
Upon starting the tightening operation, the CPU 1 monitors the value of torque t by means of the torque sensor 5 incorporated in the nut runner 4. At step S6, the CPU 1 determines whether the torque t is equal to or greater than T(j). If the answer at step S6 is YES, then the program proceeds to Step S7 where a check is made to determine whether the torque T is equal to or greater than the target torque T.
If the answer at step S7, then the value of j is incremented by 1 at step S8 and the program returns to step S5. Steps S5-S8 are repeated until the torque reaches or exceeds the target value T(n). When the answer at step S7 is YES, then the program proceeds to step S9 where the motor is stopped.
At step S10, a logical test is made to determine whether a difference between the final detected torque t and the target torque T(n) is equal to or less than the tolerable error E. If the difference is greater than the tolerable error E, the program proceeds to step S15 where a logic test is made to determine whether the difference is less than the error resulted from the previously chosen curve. If the answer at step S10 is YES, then Curve P(s+1) is selected at step S11. A check is made to determine whether Curve P(s+1) is actually Pmax or a higher curve. If the answer is No at step S12, then the control proceeds to step S3 to repeat steps S3-S12 till Curve P(s+1) is actually Curve Pmax or a higher curve.
If the answer at step S12 is YES, then Curve Pmax is stored at step S14 and the learning cycle completes.
If the answer at step S15 is YES, the control jumps to S16 where the previously tested Curve is finally employed and stored at step S14.
If the answer at step S15 is NO, then Curve P(s-1) is selected at step S17 and the control proceeds to step S18 where a check is made to determine whether the curve is actually Curve Pmin or a lower curve. If the answer at step S18 is No, then the control jumps to S3 and steps S3-S10 and S15-S18 are carried out till the curve is actually Pmin or a lower curve. If the answer at step S18 is YES, then tightening operation failed and the control carries out the alarm operation. If the answer is YES at step S15, the program jumps to step S16.
In tightening the bolt in accordance with the optimum curve determined through the aforementioned learning cycle, insufficient tightening results as shown in FIG. 6 due to a loss in torque which occurs shortly after the target torque is reached. This is due to the fact that the work is squeezed and brought into intimate contact with the bolt or nut. Therefore, in the present invention, the output torque with the nut runner still attached to the work is used to provide additional rotations to compensate for the loss in torque.
That is, the motor current is allowed to continue to flow for a short time period 1 after the target torque is reached. This prevents the torque of the bolt from decreasing, thereby, ensuring that the bolt is tightened with the target torque.
While the invention has been particularly shown and described in reference to preferred embodiments thereof, it will be understood by those skilled in the art that changes in form and details may be made therein without departing from the spirit and scope of the invention. | A method of tightening a bolt in an optimum time length does not require an additional program for controlling speed once optimum internal parameters have been determined through several learning cycles. A target torque is first preset and the nut runner is subjected to several learning cycles so that the nut runner automatically determines such internal parameters as to stop the motor immediately after the target torque is reached, requiring a minimum time for tightening the bolt. | 1 |
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation of application Ser. No. 09/614,097, filed Jul. 11, 2000.
FIELD OF THE INVENTION
[0002] This invention relates generally to systems and apparatus used as an accessory for sporting games. More particularly, the invention relates to a portable package and system for picking up and dispensing golf balls. The present invention is particularly, though not exclusively, useful for gathering or retrieving golf balls and then dispensing the golf balls one by one so that the user may, for example, practice with or make some other use of the dispensed balls.
BACKGROUND OF THE INVENTION
[0003] Golf ball retrievers are well known devices in the prior art. Generally, such devices are intended for retrieving golf balls from such locations as fairways, practice greens, and the like. Retrievers generally comprise a hollow tube having an internal diameter slightly larger than a golf ball. The tube is connected at one end to an opening in the bottom wall of a container. The container is often referred to as a shag bag. The free end of the tube usually has means for capturing the golf ball within the tube so that when the free end of the tube is placed over a golf ball on the ground and pressure applied, the ball enters and is held in the tube so it does not exit through the free end. Once a golf ball is captured, the tube is ready to pick up the next ball. When inverted, the balls are transmitted through the tube and collected in the shag bag or other container for later use.
[0004] Devices for collecting and then dispensing golf balls one at a time are known, but have many disadvantages. Thus, Liu, et al., in U.S. Pat. No. 5,395,146, entitled Golf Ball Pick-Up Device, discloses a closed rigid container-like shag bag having a spiral pathway therein. The container is intended for receiving golf balls from the transmission tube. A horizontally disposed rotating disk-like slide is provided between the transmission tube, through the hole is the disk and into and the container. The slide has a hole in it. The bottom wall of the container has two holes. The slide has two positions. In the first position, a retrieved ball enters the first hole in the bottom wall from the transmission tube and into the container. To dispense a ball, the entire container must be inverted so that balls in the tube are sent through the first hole in the disk and collected in the container. The container is then returned to its upright position and the balls proceed down the spiral path to the second hole in the bottom wall of the container. To dispense the balls, the slide must be positioned so that the second hole of the container is in registry with the hole in the disk so that balls coming from the downward spiral of the container will enter the tube. In the wall of the tube, covering a dispensing hole in the side of the tube and adjacent the tube's free end, is a pivotally mounted cover. When the cover is opened, the cover blocks access from within the tube to its free or ball retrieving end and diverts dispensed balls out the cover. A disadvantage of this device is that it is highly cumbersome to use. The balls must traverse the tube when used as a retriever, enter the container, reach the top of the container, and, through physical inversion, be moved through the entire helical path within the container. To dispense requires positioning of the slide from the first to the second position in the proper sequence. If a ball is not in the proper position within the container, the process must be repeated. If not, all the balls are guided to the dispensing portion of the container, then more than one ball will be dispensed at a time.
[0005] Tiller, in U.S. Pat. No. 5,147,101 for Golf Ball Dispensing and Retrieving System, discloses a hollow tube for collecting and dispensing golf balls. The tube has a spring-loaded latch at one open end. Pressing the one open end against a golf ball causes the ball to pass the latch and enter the tube. The collected balls are held within the tube by the latch. To dispense a ball, the tube is placed at an angle to the ground with the open end at the ground. The latch is pressed to dispense a ball. One disadvantage of the Tiller device is that the amount of balls that may be stored is limited by the length of the tube. Another disadvantage is that dispensing a ball, using the latch, requires the user to bend to the ground to dispense a ball. Additionally, while dispensing will take place on perfectly level ground, such as an indoor surface, any uneven surface may block the opening the dispenser. The support taught by Tiller (a U-shaped stand) to hold the tube at angle is inherently unstable in uneven topographical settings such as out of doors.
[0006] Another device is disclosed by Fowler et al., in U.S. Pat. No. 2,962,321 for Device for Retrieving and Storing and Dispensing Golf Balls, in which the tube used to retrieve balls has a latch at the end so that the retrieved balls are retained and then may be dispensed by manipulating the latch. The disadvantage of this device is that the balls exit the same end of the tube through which they are retrieved. To dispense balls means that the entire tube, with the captured balls, must be elevated. This is can prove clumsy, particularly when the tube retains a great many balls. The device also requires a number of manipulative steps to work, including picking the tube up and holding it elevated while dispensing balls, then putting the device down so that the dispensed ball may be used.
SUMMARY OF THE INVENTION
[0007] It is an object of this invention to provide a golf retriever/dispenser to provide a device for efficiently retrieving and dispensing golf balls.
[0008] It is yet another object of this invention to provide a golf retriever/dispenser for reprieving golf balls through a first tube and dispensing the balls through a second tube.
[0009] It is still another object of this invention to provide a dispensing mechanism for selectively dispensing one ball at a time.
[0010] It is yet another object of this invention to provide a golf ball pick-up device that can be used as a golf ball dispenser.
[0011] In accordance with one of the teachings of this invention there is provided a golf ball collection and dispensing system of the type having a hollow container for receiving and dispensing therefrom golf balls for use upon a support or playing surface, the container has at least one hole in a wall thereof so dimensioned as to allow the collection or dispensing of golf balls. The system comprises first and second hollow transmission tube means being so dimensioned so as to receive therethrough golf balls. The first and second transmission tube means each have one end for being alternatively releasably connectable to the container and in communication with the container hole. The first transmission tube means having an opposed free end comprises means for receiving at least one golf ball at a time therein such that, upon a golf ball being inserted into the free end, the receiving means retains the golf ball and are capable of accepting therethrough and retaining therewithin the next golf ball. A second hollow transmission tube means is provided which comprises means for dispensing therefrom at least one golf ball at a time.
[0012] In yet another embodiment of this invention there is provided a dispensing means of the type which may be used to dispense rotatable objects such as, for example, balls having predetermined dimensions, in which the balls are passed through a tube or similar conduit. The dispensing means comprises the tube. There is also provided first and second blocking means for, in a first position, holding all balls from being dispensed from the free end of the tube and, in a second position, the blocking means selectively dispensing from the tube at least one ball at a time. There is further provided means for moving said first and second blocking means between said first position to said second position.
[0013] In still another novel aspect of this invention there is provided a device for dispensing balls of the type having a bag or container at one end for retaining balls and a conduit through which the balls are dispensed. The dispenser comprises a spike fixedly joined at one end of the dispenser for removably attaching the dispenser to a play surface to thereby provide stability for the dispenser.
[0014] The novel features of this invention, as well as the invention itself, both as to its structure and its operation, will be best understood from the accompanying drawing taken in conjunction with the accompanying description, in which similar reference characters refer to similar parts, and in which:
BRIEF DESCRIPTION OF THE DRAWING
[0015] In the drawing:
[0016] [0016]FIG. 1 is a perspective view of the ball retriever partially sectioned to show the retrieving of a golf ball and constructed in accordance with the teachings of the invention;
[0017] [0017]FIG. 2 is a side view of the ball retriever;
[0018] [0018]FIG. 3 is a side view of the ball dispenser mode of the invention;
[0019] [0019]FIG. 4 is a section taken along line 4 - 4 and looking in the direction of the arrows in FIG. 3;
[0020] [0020]FIG. 5 is a bottom view of the golf ball holder;
[0021] [0021]FIG. 6 is a section taken along line 6 - 6 in FIG. 5 and looking in the direction of the arrows;
[0022] [0022]FIG. 7 is a section through the ball dispenser with the release mechanism in a ball dispensing position; and
[0023] [0023]FIG. 8 is a section through the ball dispenser with the release mechanism preventing golf balls from being dispensed.
DETAILED DESCRIPTION OF THE INVENTION
[0024] In accordance with this invention there is provided a ball retriever/dispenser 10 (FIGS. 1 - 4 ) in which a golf shag bag 12 may comprise a generally cylindrical container 14 (FIGS. 1 - 4 ). The exterior wall 14 of the bag 12 may be made of a flexible fabric material, such as nylon or the like, or may be constructed of a rigid plastic. Integrally formed with the exterior cylindrical wall is a top wall 16 and bottom wall 18 of the same fabric or rigid material. These walls 14 , 16 , 18 form a container or shag bag for receiving golf balls. The shape of the bag 12 may be any desired shape and preferably cylindrical. The shape of the bag 12 may maintained by an upper and lower disks 20 and 22 , respectively (FIG. 4). The exterior top and bottom walls 16 and 18 are generally the same dimensions as the disks 20 and 22 . The disks 20 , 22 may be made of any rigid material, such as plastic. Generally C-shaped side bars 24 (only one is visible in FIG. 4) having an elongated linear center section 2 , 6 provides support for the side wall 14 so that the side wall 14 maintains its generally cylindrical shape. A generally U-shaped handle 28 , has screw threaded ends 30 which extend through apertures (not visible) in the top wall 16 of the bag 12 , and through holes (not visible) in registry in the top disk 20 and a hole (not visible) in the bent end 32 of the C-shaped bar 24 . Nuts 34 are used to secure the bolt ends 30 of each leg 36 and 38 of the top end 32 of the C-shaped bar 24 , the top disk 20 and top fabric wall 16 . In a similar fashion, threaded bolts 40 are inserted through apertures 42 , 44 (FIGS. 5, 6) in the bottom disk 22 and through apertures (not visible) in the bottom ends 46 of the generally C-shaped bars 24 . The two opposed C-shaped bars 24 , secured to the top and bottom disks 20 and 22 , maintain the cylindrical shape of the side wall 14 of the bag 12 . The bottom disk 22 (FIGS. 5 and 6) may have extending right angle triangularly shaped fin elements 48 to give strength and rigidity to the bottom disk 22 and forming a directional path from the outer wall 14 toward the disk center. The ends 46 of each C-shaped bar 24 fit within two substantially parallel arranged fins 50 (FIG. 5) which are intended to properly orient the bottom ends 46 of the C-shaped bars 24 .
[0025] The cylindrical outer wall 14 of the bag 12 may have there through an opening closed by a vertically disposed zipper 52 (FIGS. 1 and 3) to provide access to the interior 54 (FIG. 4) of the bag 12 . Attached to the outer wall 14 may be a container, such as, for example, a substantially rectangular net bag 62 secured thereto, as by stitching or the like, for receiving such articles as golf balls, Ts, or one of the tubes 68 or 74 (when such tube 68 or 74 is not in use), or the like (FIGS. 1 - 3 ). The bag 12 may also have attached thereto, as by stitching, an extending tang 64 with a hanging C-hook 66 . The tang 64 with its hook 66 may be attached at the juncture of the top wall 16 and side wall 14 , as is commonly known, for the purpose of hanging up the retriever/dispenser 10 .
[0026] The bottom disk 22 may have a centrally disposed circular aperture 56 sufficiently large enough to admit a golf ball. Integrally formed with the bottom disk and extending downwardly may be a golf ball dispensing and receiving collar 58 of sufficient diameter to permit the passage there through of one golf ball at a time. The exterior wall of the collar 58 may be threaded 60 (FIG. 6).
[0027] There is provided a golf ball retrieving tube 68 , having a golf ball retriever mechanism 70 of well-known configuration at one end, for retrieving golf balls 72 . The opposed end 74 may have an enlarged and internally threaded collar for being received by the threaded end 60 of the lower disk collar 58 .
[0028] A dispensing tube 74 (FIGS. 3, 4, 7 , and 8 ) may comprise a substantially L-shaped dispensing tube 76 . The vertical leg 78 and laterally extending leg 80 of the L-shape dispenser 76 (i.e, the first and second legs 78 , 80 ) may be joined as at an integrally formed elbow 82 . The interior of the hollow tube 74 is so dimensioned that golf balls 72 may pass easily between the bag 12 , past the elbow 82 and out the second or laterally extending dispensing leg 80 . The dispensing leg 80 may extend downwardly at an acute angle from the horizontal to aid in the dispensing of balls 72 . The vertical leg 78 may continue below the elbow 82 to form a dimensionally uniform vertical tube 84 . The end of the tube 84 may be fixedly terminated in a spike 86 which is secured to the free lower end of thee tube 84 by attachment means such as screws or the like (not shown).
[0029] The dispenser tube 74 is provided with a dispenser mechanism 88 . The mechanism 88 may comprise a slot 90 (FIG. 3) through the upper wall of the laterally extending second leg 80 . The slot 90 may be spaced from the elbow 82 and may extend to the dispensing free end 98 of the leg 80 . A substantially planar bar member 92 , which may be made of any rigid material, such as plastic, may have two downwardly blocking means such as extending prongs 94 and 96 . The prong 94 , positioned closest to the elbow 82 , is shorter than the prong 96 disposed closest to the dispensing end 98 . Integrally formed on opposed sides of the slot 90 and to the upper portion 78 of the L-shaped dispensing tube and the laterally extending dispensing leg 80 may be two parallel support brackets 100 . The bar 92 may be pivotally secured between the brackets 100 as by a pivot pin 102 which may be disposed between and substantially perpendicular to the prongs 94 , 96 . The rear most prong 94 extends into and adjacent the end of the slot 90 proximate the elbow 82 . A spring 104 may have one end disposed on the upper surface 106 of the dispensing leg 80 and its opposed end abutting the underside of the end 106 of the bar 94 adjacent the elbow 82 . The spring 104 may be held in position as by engaging bosses molded into the respective outer surface 106 of the leg 80 and the bar 94 . A lever arm 108 may be positioned above the bar 94 and pivotally secured to the brackets 100 as by a pivot pin 110 so that one end of the lever 108 engages the upper surface 112 of the bar 94 proximate th elbow 82 .
[0030] The free upper end 114 of the L-shaped dispensing tube 76 may be fitted with a collar which is internally threaded 116 for engaging the threaded end 60 of the collar 58 .
[0031] In operation, the golf ball retrieving tube 68 is releasably secured to the collar 58 by being threaded into position. Golf balls 72 are retrieved through the golf ball retrieving mechanism 70 in a manner well known in the art. Balls 72 are then stored in the bag 12 by inverting the tube and allowing the balls 72 to roll into the bag 12 . When a desired number of balls 72 have been collected in the bag 12 , the bag 12 is inverted and the retrieving tube 68 is unscrewed from the collar 58 and the dispensing tube 74 is screwed on in its place. The bag 12 is then set upright and the balls 72 fall through the central aperture 56 and are guided by the right angle fins 48 in the bottom disk 20 through the disk collar 58 and into the dispensing tube 76 . The spike 86 is pushed into the ground to provide a steady positioning and securing means for the dispenser 10 . The spike 86 also spaces the dispensing end 98 of the L-shaped dispenser from the ground. The balls 72 are prevented from leaving the L-shaped dispensing leg by the longer prong 96 of the pivotally mounted bar 92 . To dispense a ball 72 , the lever arm 108 is depressed at its forward end 116 in the direction of the arrow 118 (FIG. 7). This movement depresses the end 106 of the bar 94 adjacent the elbow 82 , compressing the spring 104 . The space between the prongs 94 , 96 is such as to admit one ball 72 at a time. If desired, the space may be so dimensioned as to allow more than one ball so that more than one ball will be dispensed each time. The shorter prong 94 enters the slot 90 in the dispensing downward tube 80 just behind the ball 72 ready to be dispensed, blocking the ball 118 immediately behind it. The shorter prong 94 , therefore, substantially simultaneously enters the interior of the second leg to hold the ball 118 back while the first ball 72 is dispensed because the longer prong 96 has been pivoted out of position. When the lever arm 108 is released, the spring 104 pushes up the end 106 of the bar 92 , dropping the longer prong 96 into the slot 90 to thereby block the next ball 118 from being dispensed. The process is repeated each time the golfer wishes to have a ball dispensed and, as preferably configured, only one ball can be dispensed at a time.
[0032] When the golfer finishes using the retriever/dispenser, the dispensing tube 74 and retrieving tube 68 may be conveniently stored in the bag 12 by means of the zipper opening 52 . Thus, the combination of all parts in the single dispenser 10 results in a self-contained and efficient retriever/dispenser.
[0033] While the particular golf ball dispensing and retrieving system, as well as the particular ball dispensing device, as herein shown and disclosed in detail is fully capable of obtaining the objects and advantages hereinbefore stated, it is to be understood that same is merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended to the details of the construction or design herein shown other than is defined in the appended claims. | A combination golf ball retriever and dispenser comprises a shag bag and two tubes. The first tube is a conventional golf ball retrieving tube which may be screwed into a collar at the base of the bag. Golf balls retrieved through the tube may be stored in the bag by inverting the retrieving tube. Stored golf balls may be dispensed by removing the retrieving tube and screwing into its place a dispensing tube on an extending collar which surrounds a hole at the bottom of the bag. A selective dispenser is secured to the end of the second leg and comprises a pivotally mounted spring loaded bar having two prongs. A pivotally secured lever arm may press down on the arm thereby compressing the spring and moving one prong out of the interior of the second leg and the second prong through the slot and into the interior of the second leg. | 0 |
BACKGROUND
[0001] 1. Technical Field
[0002] The present invention relates to a saddle for equestrian use and more particularly it relates to a design of saddle flap which allows the contours of the flap easily to be adjusted.
[0003] 2. Description of the Related Art
[0004] Conventionally, an equestrian saddle comprises a saddle flap extending downwardly from each side of the seat and overlying a saddle panel at that side. The outer surface of the flap may be profiled with padding in its forward part to overlie a block fixed to the panel beneath the flap and which contours the forward end portion of the flap for engagement by the leg of the rider. Ideally, a different contouring is needed for different uses of the saddle to provide grip by the part of the rider's leg appropriate to that usage. Accordingly, for example, the size and/or position and/or shape of a block of a saddle primarily intended for use in dressage will be different to that in a saddle primarily intended for use in jumping and both will be different to the block, if provided, in a general purpose saddle. Conventionally, this means that a different saddle may be produced for different primary uses. U.S. Pat. No. 5,740,665 proposes a design of saddle flap in which the contour at its forward end portion can be modified in order to change the saddle to suit a different primary use. In this previously proposed saddle, the flap is provided with a removable forward part which is contoured by means of a block to suit a specific usage, a range of different forward parts being provided each with a different contour with the user selecting whichever forward part best suits the intended use at that time and mounting that to the remainder of the flap panel. While this proposal provides a saddle which can be adjusted by the user to suit a number of different primary uses nevertheless it is quite an expensive solution as a range of different replaceable flap parts must be acquired and, moreover, it is not really practical for a saddle manufacturer to provide more than a small number of different configurations of contouring.
BRIEF SUMMARY
[0005] According to the present invention there is provided an equestrian saddle having flaps, and a block mounted to each flap for engagement by the leg of the rider, the block being mounted to the flap by a mounting system which permits the position of the block on the flap to be adjusted and which retains the block in its selected position on the flap by a clamping action between the block and the flap.
BRIEF DESCRIPTION OF THE DRAWINGS
[0006] An embodiment of the invention will now be described by way of example only with reference to the accompanying representations in which:
[0007] FIG. 1 shows a saddle flap of a saddle in accordance with a preferred embodiment, an adjustable block on the saddle flap being shown in a forward adjusted position;
[0008] FIG. 2 is a view similar to FIG. 1 but showing the block in a rear adjusted position;
[0009] FIG. 3 is a view of a substantially rigid clamping plate within the base of the block;
[0010] FIG. 4 is a view of the inner side of the flap;
[0011] FIG. 5 shows the saddle flap with the block removed to show elongate apertures within the flap to achieve the required adjustment;
[0012] FIG. 6 is a view similar to FIG. 5 of a modified form of flap with two sets of apertures to provide a greater range of adjustment;
[0013] FIG. 7 is a view showing the block removed from the flap;
[0014] FIG. 8 shows the saddle flap of FIG. 1 , diagrammatically depicting pivotal adjustment of the block on the saddle flap; and
[0015] FIG. 9 shows in detail alternative shapes of the apertures formed in the flap to achieve adjustability of the block position relative to the flap.
DETAILED DESCRIPTION
[0016] The representations show a saddle flap 2 in accordance with a preferred embodiment of the invention. The saddle flap 2 is attached to the seat of the saddle at one side to overlie the saddle panel at that side. A flap of corresponding, but mirror image, form to that shown is attached to the seat at the other side of the saddle. A block 4 for engagement by the leg of the rider is adjustably mounted to the outer side of the flap. The adjustable mounting system which will be described in detail shortly also enables the block to be removed for possible replacement by a block of different size and/or shape.
[0017] The block 4 which is shown in FIG. 7 is formed with a rigid or semi-rigid core which may be covered at least on its rearwardly facing surface with a layer of a resiliently compressible material such as an open cell plastics foam, with the block being enclosed within an outer covering to match the exterior of the saddle. This construction of the block provides a cushioning effect for the leg of the rider when applied against the rear face of the block. Advantageously, the rear face of the block is contoured into concave shape in the manner described in our U.S. Pat. No. 7,562,514 so as to better locate the leg of the rider. While this is particularly beneficial in a saddle being used for dressage, it is also of benefit in saddles for other uses. It is however to be understood that the foam layer which provides the cushioning effect is not essential and may be omitted as the concave shape enables the thigh of the rider to comfortably rest against it.
[0018] A substantially rigid plate 8 , preferably of metal (see FIG. 3 ), is incorporated within the base of the block 4 and includes internally-threaded sleeves 10 on its inner surface. The plate 8 is covered by an external covering 12 which forms the base surface of the block and is apertured to permit passage of clamping screws 14 into the threaded sleeves.
[0019] A rigid plate 16 (see FIG. 4 ), likewise preferably of metal is mounted at the inner side of the flap and carries the clamping screws 14 which pass through apertures in the flap into engagement within the threaded sleeves 10 in the plate 8 in the base of the block. When the screws 14 are tightened the flap is clamped tightly between the two plates 8 , 16 thereby securing the block firmly to the flap.
[0020] With reference to FIG. 5 , the apertures 18 in the saddle flap for passage of the screws 14 are of a size greater than the shank diameter of the screws to permit adjustment of the position of the block on the flap by lateral movement of the screws within the apertures. In the preferred embodiment, the apertures 18 are elongate in a forward/rear direction to permit adjustment of the position of the saddle block on the flap in a forward/rear direction. FIG. 1 shows the block in its forwardmost position of adjustment and FIG. 2 shows the block in its rearmost position of adjustment and it will be appreciated that the block can assume any intermediate position between these two positions. Although the apertures could also be configured to permit vertical adjustment if required, the forward/rear adjustment is the primary adjustment which will normally be required.
[0021] FIG. 6 shows a modification with two sets of apertures 18 a, 18 b to provide the possibility of positioning the block in a selected one of the two vertical positions on the flap depending on which set of apertures is used. These apertures are also shaped to allow the possibility of adjustment of the inclination of the block.
[0022] With reference to FIGS. 8 and 9 , the apertures 18 may be in the form of specially shaped slots to allow the block 4 to be angled over a substantial range to mirror the directional angle of the rider's leg, dictated by the length of leg/stirrup and individual riding position. In particular the top of the block 4 can be pivoted about a pivot point at the bottom of the block, or the bottom of the block can be pivoted about a pivot point at the top of the block, between forward and rearward positions. By appropriately configuring the angular extent of the slots, an angular range of adjustment of up to about 40° can be achieved and this dramatically changes the angle of the block 4 against the rider's leg. As shown in FIG. 8 , the block 4 may be angled by pivoting the block 4 between a forward (“standard”) angle 20 and a rearward angle 22 toward the rider's leg. The block 4 could also be pivoted forward from the “standard” angle 20 away from the rider's leg.
[0023] FIG. 9 shows the special shaping of the apertures with a wider rearward end and a narrower forward end, in a generally teardrop shape 18 . This shape is of particular benefit in enabling the angle of the block 4 to be adjusted without allowing any substantial change in the height of the block on the flap. This may be understood by pivoting the block about its lower end with the associated screw within, and located by, the narrower forward end of the lower aperture 18 and alternatively by pivoting the block about its upper end with the associated screw within, and located by, the narrower forward end of the upper aperture, in each case the width of the aperture at its forward end being substantially equivalent to the shank diameter of the associated screw. Even with a degree of backwards adjustment, no substantial height change will occur. This facility for adjustment, particularly angular adjustment, without any substantial height change is significant because it facilitates uniformity of setting of the blocks at the two sides of the saddle. However, in an alternative example, the apertures 18 may have other shapes such as, for example, a simple straight slot shape, with the loss of some of the benefits afforded by the teardrop shape.
[0024] The size of the base of the block in relation to the size of the apertures in all preferred embodiments is such that in any adjusted position of the block the entirety of the apertures will be concealed beneath the base of the block so that no part of the adjustment system is visible from the exterior of the saddle and therefore does not detract from the aesthetic appearance of the saddle.
[0025] A range of different sized/shaped blocks may be provided to enable a greater range of possible set-ups for the saddle in the zone engaged by the legs of the rider. For some uses it may even be preferred to remove the block so that the outer surface of the flap is substantially uncontoured.
[0026] The embodiment has been described by way of example only and modifications are possible within the scope of the invention.
[0027] The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavor to which this specification relates.
[0028] In the following claims, the terms used should not be construed to limit the claims to the specific embodiments disclosed in the specification and the claims, but should be construed to include all possible embodiments along with the full scope of equivalents to which such claims are entitled. Accordingly, the claims are not limited by the disclosure. | An equestrian saddle having flaps, and a block mounted to each flap for engagement by the leg of the rider, the block being mounted to the flap by a mounting system which permits the position of the block on the flap to be adjusted and which retains the block in its selected position on the flap by a clamping action between the block and the flap. | 1 |
FIELD OF THE INVENTION
[0001] This invention relates to methods of treating diseases with CD40/B7 antagonists.
BACKGROUND OF THE INVENTION
[0002] Activation of T cells
[0003] Activation of T cells is known to require multiple interactions with antigen presenting cells (“APC”). The TcR-CD3 complex has two functions in antigen-induced activation: a recognition function in which a specific antigen is recognised in the context of the appropriate MHC molecule, and a signalling function in which the recognition event is transmitted across the plasma membrane. However, to induce proliferation and maturation into effector cells, T cells need a second signal in addition to the one mediated by the TcR-CD3 complex. This costimulatory signal is normally provided by the cell surface of APC. Intercellular signalling after TcR/MHC-peptide interaction in the absence of the costimulatory signal results in T cell inactivation, which is known as T cell anergy or T cell unresponsiveness. Several accessory molecules present on the cell surface of T cells with known ligands on the APC have been implicated in providing the costimulatory signal in T cell activation.
[0004] The B7-CD29 costimulatory pathway
[0005] The best candidate costimulatory signal leading to full T cell activation, is generated by interaction of CD28 on the T cells with the B7 costimulatory molecules on APC. In vitro studies have demonstrated that signalling via the CD28 costimulatory pathway can prevent the induction of anergy.
[0006] To date, two members of the B7 family have been molecularly cloned and functionally characterized: B7.1 (CD80), originally named B7/BB1 and a second B7 molecule, named B70 or B7.2 (CD86). CD80 is a monomeric transmembrane glycoprotein with an apparent molecular mass of 45-65 kDa and is, like CD28, a member of the immunoglobulin superfamily (Freeman et al., J. Immunol. 143: 2714 (1989)). Initially it was reported that the expression of the CD80 molecule was restricted to activated B cells and monocytes stimulated with IFN-γ(Freedman et al., Cell Immunol. 137: 429 (1991)). More recently, CD80 expression has also been found on cultured peripheral blood dendritic cells (Young et al., J. Clin. Invest. 90:229 (1992)) and on in vitro activated T cells (Azuma et al., J. Ax Med. 177:845 (1993)). CD86 is a transmembrane glycoprotein with an apparent molecular mass of approximately 70 KDa and is also a member of the immunoglobulin superfamily (Freeman et al., Science 262:909 (1993)); Azuma et al., Nature 366:76 (1993)). The CD86 molecule seems to have a very similar distribution pattern to CD80, with the exception that induction of cell-surface expression seems to be faster and that it is present on freshly isolated monocytes.
[0007] It is clear from the literature that blocking CD80 exclusively only results in partial inhibition of T cell activation. Activation of T cells by alloantigen-expressing monocytes is predominantly dependent on CD86 costimulation. During an MLC with monocytes as stimulator cells, anti-CD86 Mab alone could strongly but not completely inhibit the proliferative response. However, only CTLA4-Ig (a soluble fusion protein consisting of the extra-cellular domain of human CTLA4 linked to human IgG [CH2 and CH3 domains], that can bind to both CD80 and CD86) or a combination of anti-CD80 plus anti-CD86 Mabs gave maximal inhibition.
[0008] CD40-CD40L costimulatory pathway:
[0009] From the above reviewed literature data it appears that other costimulatory molecules can be of crucial importance for the activation of T cells when costimulation via CD80/CD86-CD28 is blocked. One such an alternative costimulatory pathway is regulated by the interaction between CD40 on the APC and CD40L on the T cells. The CD40 molecule belongs to the TNF receptor family of type I transmembrane proteins. The members of this gene family, which include: the two receptors for TNF; the low-affinity nerve growth factor receptor; the T cell activation antigen CD27; CD30 and CD95, are characterized by sequence homology in their cysteine-rich extracellular domains (Armitage et al., Current Opinion in Immunology 6:407 (1994)). Interestingly, the known ligands for the members of the TNF receptor family are very homologous as well, forming another gene family named the TNF/CD40L gene family. Although TNF-α is a soluble cytokine, it is initially synthesized as a membrane associated molecule. Most of the members of the TNF/CD40L receptor family are type II transmembrane proteins.
[0010] CD40 is best known for its function in B cell activation. The molecule is constitutively expressed on all B cells. CD40L-CD40 interaction can stimulate the proliferation of purified B cells and, in combination with cytokines, mediate immunoglobulin production. Recent studies indicate that the distribution of the CD40 molecule is not so restricted as was originally postulated. Freshly isolated human monocytes express low levels of the CD40 molecule, which can be up-regulated by culturing in the presence of IFN-γ (Alderson et al., J. Ep. Med. 178:669 (1993)). Stimulation of monocytes via CD40 results in the secretion of pro-inflammatory cytokines such as IL-1 and TNF-α, toxic free radical intermediates such as nitric oxide, and up-regulation of the B7 costimulatory molecules. Human dendritic cells (DC) isolated from peripheral blood can also express the CD40 molecule (Caux et al., J. Exp. Med. 180:263 (1994)). Ligation of CD40 on DC results in enhanced survival of these cells when cultured in vitro. In addition, like with monocytes, stimulation of DC results in secretion of pro-inflammatory cytokines such as IL-1 and TNF-α and up-regulation of the CD80/86 co-stimulatory molecules.
[0011] All the above described observations clearly indicate that the CD40L molecule on activated T cells is an important effector molecule that mediates stimulatory effects via ligation of CD40 expressed on a variety of cell types involved in the immunoinflammatory response. However, there is also experimental evidence that the CD40L molecule can receive signals that result in the costimulation of the T cell itself. Using mouse P815 cells that can present anti-CD3 monoclonal antibody to human T cells via binding to Fc-receptors on its cell surface, it was demonstrated that CD40 transfected P815 cells could substantially induce proliferation and CTL activity of small resting human T cells (Cayabyab et al., J. Immunol. 152:1523 (1994)). This demonstrates that the CD40L-CD40 interactions is clearly bidirectional.
[0012] Prolonged transplant survival after blocking CD80/CD86-CD28:
[0013] Several recent in vivo models have shown that induction of prolonged graft acceptance is possible by interruption of the CD80/CD86-CD28 pathway. Treatment with CTLA-4 immediately after xenogeneic human pancreatic islet transplantation in mice resulted in long-term graft survival (Lenschow et al., Science 257:789 (1992)). However, 90% of fully mismatched rat cardiac allografts were rejected in rats treated intraperitoneally (IP) with CTLA4-Ig during 7 days (Turka et al., Proc. Natl. Acad. Sci. USA 89:11102 (1992)). CTLA4-Ig given intravenously (IV) at time of transplantation and then IP every other day on days 2 through 12, prolonged cardiac allograft survival in mice, but failed to prolong the survival of primary skin grafts (Pearson et al., Transplantation 57: 1701 (1994)). Blockage of the CD28-pathway with CTLA4-Ig resulted in significant prolongation of small bowel transplant survival in rats compared to controls, although all grafts were rejected after 15 days (Pescovitz et al., Transplant Proc. 26:1618 (1994)). Finally, treatment with CTLA4-Ig could reduce lethal murine GVHD in recipients of fully allogeneic bone marrow and significantly prolonged survival rates with up to 63% of mice surviving greater than 3 months post-transplantation (Blazar et al., Blood 83:3815 (1994)). The failure of CTLA4-Ig alone to induce anergy in vitro and in vivo, can most likely be explained by a persistent IL-2 production, induced by TCR triggering in combination with signalling from other accessory molecules on APC.
[0014] Prolonged transplant survival after blocking CD)40-CD40L:
[0015] Recent work has also demonstrated that blocking the CD40-CD40L pathway is strongly immunosuppressive in transplantation models. Combined treatment with allogeneic small lymphocytes or T cell-depleted small lymphocytes plus an antibody to mouse CD40L permitted indefinite pancreatic islet allograft survival in 37 out of 40 recipients that differed in major and minor histocompatibility loci (Parker et al., Proc. Nat. Acad. Sci. USA 92:9560 (1995)). From these experiments it was concluded that the effective blocking of the CD40L-CD40 interaction most likely had resulted in preventing the induction of costimulatory molecules on the small resting lymphocytes by the alloreactive host T cells. In another recent study, it was demonstrated that administration of a blocking Mab to mouse CD40L at the time of transplantation markedly prolonged survival of fully disparate murine cardiac allografts in both naive and sensitized hosts. However, when anti-CD40L therapy was delayed until postoperative day 5, anti-CD40L failed to prolong graft survival. From this study, it was concluded that anti-CD40L therapy inhibited allograft rejection primarily by interfering with T cell help for effector functions.
[0016] Long-term acceptance of allografts without signs of chronic rejection after blocking CD80/CD86-CD28 and CD 40-CD 40L:
[0017] Blocking either of the two major T cell costimulatory pathways, CD80/86-CD28 or CD40-CD40L, alone is not sufficient to permit indefinite engraftment of highly immunogenic allografts. However, it was recently shown that blocking the CD80/CD86-CD28 and CD40-CD40L pathways simultaneously effectively aborts T cell clonal expansion in vitro and in vivo, promotes long-term survival of fully allogeneic skin grafts, and inhibits the development of chronic vascular rejection of primarily vascularized cardiac allografts (Larsen et al., Nature 381:434 (1996)). In the vascularized murine cardiac allograft model, C3HJ recipients treated with CTLA4-Ig alone (Mean Survival Time (MST) 50d), anti-CD40L Mab alone (MST 70d), or the combination (MST>70d), all showed prolonged survival of BALB/c cardiac allografts compared with untreated controls (MST 12d). Interestingly, when examined histologically at day 58-62 posttransplantation, marked differences were apparent. Allografts from CTLA4-Ig-treated mice showed extensive lymphocytic infiltration, interstitial fibrosis, and severe coronary arterial intimal thickening and fibrosis, all clear signs of a chronic rejection process. Anti-CD40L-treated recipients had less lymphocytic infiltration and interstitial fibrosis, but also had coronary vasculopathy characteristic of chronic rejection. In contrast, the allografts from mice in which the CD80/86-CD28 and CD40-CD40L pathways were blocked simultaneously, the parenchyma and blood vessels were virtually indistinguishable from those found in normal BALB/c hearts.
[0018] Current concepts on immunological tolerance hold that anergy is the result of intercellular signalling after TcR/MHC-peptide interaction, in the absence of a so-called co-stimulatory signal. As described above, both the CD80/CD86-CD28 costimulatory pathway and the CD40L-CD40 costimulatory pathway are important for the activation of T cells and play a role in the prevention of anergy. Stimulation of T cells via the TcR/CD3 complex results in a low and transient expression of CD40L. It has previously been demonstrated that stimulation of T cells via TcR/CD3 and costimulation with CD80/CD86-CD28 results in a strong and prolonged expression of the CD40L molecule. Low levels of CD86 can be found constitutively on various APC populations. Furthermore, stimulation of APC via CD40 is one of the strongest signals to up-regulate CD80 and CD86. Likewise, low levels of CD40L are expressed on T cells after first encounter of antigen (TcR/CD3 activation), even without complete costimulation. This CD40L expression can not only receive a signal from the APC via CD40, but can also stimulate the APC to enhance the CD86 expression and most importantly up-regulate CD80 expression. At the same time, low levels of CD86 expression on professional APC can prevent the induction of T cell anergy and up-regulation of CD80 and CD86 expression strongly stimulates the T cells to secrete cytokines and to enhance CD40L expression. It is therefore concluded by the present inventors that these two interactions (CD40L-CD40 and CD80/CD86-CD28) are connected in the initiation and amplification of T cell mediated immune responses. Thus, only blocking the CD40L-CD40 interaction will not completely prevent activation of the T cells via CD80/CD86-CD28, and only blocking the CD80/CD86-CD28 interaction will n completely prevent the activation of the effector functions of the APC population. For optimal immunosuppression, the CD80/CD86-CD28 and CD40L-CD40 interaction need to be blocked simultaneously.
[0019] In the above described in vivo experiments a combination of a monoclonal antibody to mouse CD40L was used in combination with CTLA4-Ig to block both CD80 and CD86. However, the generation of a single pharmaceutical agent by combining the ligand binding domains of CTLA4-Ig and that of an anti-CD40L monoclonal antibody will result in the cross-linking of T cells and APC. This will undoubtedly result in the activation of the T cells, which is exactly the opposite of the desired effect. Furthermore, all of the above referenced publications clearly suggest that blocking both CD80 and CD86 results in a better immuno-suppression than blocking each of them separately. Also, it has been demonstrated that only blocking both CD80 and CD86 can result in T cell anergy. It was therefore surprising to find that in combination with an antagonistic anti-CD40 monoclonal antibody, blocking only CD86 resulted in T cell anergy despite the fact that CD80 was not blocked. This had led to the present invention that consists of pharmaceutical molecules that have the capacity to bind and block both the CD40 and the CD86 molecules.
SUMMARY OF THE INVENTION
[0020] The invention is based on the discovery that a molecular combination of an antagonistic molecule binding to CD40 and an antagonistic molecule binding to CD86, both expressed at low levels on professional APC, can inhibit the activation of T cells and result in T cell anergy. Accordingly, this combination can be used to prevent or treat diseases or conditions in which the activation of T cells is involved, including transplant rejection, multiple sclerosis, psoriasis, rheumatoid arthritis and systemic lupus erythematosus
[0021] One embodiment of this invention is a single soluble molecule or ligand capable of binding to the human CD40 and CD86 antigens located on the surface of antigen presenting cells. A preferred embodiment is a single protein encompassing a combination of a therapeutically active antagonistic monoclonal antibody to CD40 or fragments thereof and a therapeutically active antagonistic CD86 ligand, including a monoclonal antibody to CD86, the CTLA4-Ig molecule, or fragments thereof In a related embodiment, gene therapy techniques are used to produce such a single protein in vivo.
[0022] A more preferred embodiment is a single protein encompassing a combination of a therapeutically active antagonistic monoclonal antibody to CD40 or fragments thereof and the therapeutically active antagonistic anti-CD86 monoclonal antibody Fun-1 (Nozawa et al., J. Pathol. 169:309 (1993)) or a therapeutically active fragment thereof. Again, gene therapy can be used to produce such single protein in vivo.
DETAILED DESCRIPTION OF THE INVENTION
[0023] All publications and applications, cited previously or below are hereby incorporated by reference. One embodiment of the bispecific molecules of the invention is formed by conjugating two single chain antibodies, one derived from an antibody specific for CD40 and the other from an antibody specific for an CD86. Another embodiment is a fusion protein including a monoclonal antibody to CD40, or a fragment thereof, and an antibody to CD86, or a fragment thereof. In either case, a CTLA4-Ig molecule can be substituted for the antibody to CD86. The monoclonal antibodies used to form the bispecific molecules include, in whole or in part, as appropriate, chimeric antibodies, humanized antibodies, human antibodies, single-chain antibodies and fragments, including Fab, F(ab′) 2 , Fv and other fragments which retain the antigen binding function of the parent antibody. Single chain antibodies (“ScFv”) and the method of their construction are described in U.S. Pat. No. 4,946,778.
[0024] Chimeric antibodies are produced by recombinant processes well known in the art, and have an animal variable region and a human constant region. Humanized antibodies correspond more closely to the sequence of human antibodies than do chimeric antibodies. In a humanized antibody, only the complementarity determining regions (CDRs), which are responsible for antigen binding and specificity, are non-human derived and have an amino acid sequence corresponding to the non-human antibody, and substantially all of the remaining portions of the molecule (except, in some cases, small portions of the framework regions within the variable region) are human derived and have an amino acid sequence corresponding to a human antibody. See L. Riechmann et al., Nature; 332: 323-327 1988; U.S. Pat. No. 5,225,539 (Medical Research Council); U.S. Pat. Nos. 5,585,089; 5,693,761; 5,693,762 (Protein Design Labs, Inc.).
[0025] Human antibodies can be made by several different methods, including by use of human immunoglobulin expression libraries (Stratagene Corp., La Jolla, Calif.; Cambridge Antibody Technology Ltd., London, England) to produce fragments of human antibodies (V H , V L , Fv, Fd, Fab, or (Fab′) 2 ) and use of these fragments to construct whole human antibodies by fusion of the appropriate portion thereto, using techniques similar to those for producing chimeric antibodies. Human antibodies can also be produced in transgenic mice with a human immunoglobulin genome. Such mice are available from Abgenix, Inc., Fremont, Calif., and Medarex, Inc., Annandale, N.J. In addition to connecting the heavy and light chain Fv regions to form a single chain peptide, Fab can be constructed and expressed by similar means (M. J. Evans et al., J. Immunol. Meth., 184:123-138 1995).
[0026] All of the wholly and partially human antibodies described above are less immunogenic than wholly murine or non-human-derived antibodies, as are the fragments and single chain antibodies. All these molecules (or derivatives thereof) are therefore less likely to evoke an immune or allergic response. Consequently, they are better suited for in vivo administration in humans than wholly non-human antibodies, especially when repeated or long-term administration is necessary, as may be needed for treatment with the bispecific antibodies of the invention.
[0027] U.S. Pat. No. 5,534,254 (Creative Bimolecules, Inc.) describes several different embodiments of bispecific antibodies, including linking single chain Fv with peptide couplers, including Ser-Cys, (Gly) 4 -CyS, (His) 6 -(Gly) 4 -Cys, chelating agents, and chemical or disulfide couplings including bismaleimidohexane and bismaleimidocaproyl. Another embodiment is a dimer having single chain FvL 1 and FvH 2 linked and FvH 1 linked with FvL 2 . All such linkers and couplings can be used with the bispecific antibodies of the invention.
[0028] The bispecific molecules of the invention are administered as a pharmaceutical composition at a dosage effective to inhibit the activation of T cells. The effective dosage can be readily determined in routine human clinical trials or by extrapolation from animal models. The dosage and mode of administration will depend on the individual. Generally, the compositions are administered at a dose between 0.1 mg/kg and 10 mg/kg. Typically, the pharmaceutical composition is administered by injection, either intravenously, subcutaneously or intraperitoneally. It may also be possible to obtain compositions which may be topically or orally administered, or which may be capable of transmission across mucous membranes. If administered by continuous infusion, the infusion may proceed at a dose between 0.05 and 1 mg/kg/hour.
[0029] Before administration to patients, formulants and excipients, well known in the art, are preferably added to the pharmaceutical composition. Additionally, pharmaceutical compositions can be chemically modified by covalent conjugation to a polymer to increase there circulating half-life. Polymers, and methods to attach them to peptides, are shown in U.S. Pat. Nos. 4,766,106; 4,179,337; 4,495,285; and 4,609,546, and include polyoxyethylated polyols and PEG.
[0030] Monoclonal antibodies against human CD40 are described in U.S. Pat. No. 5,677,165. Antibodies against CD86 can be made by similar methods. The CTLA4-Ig molecule can be made by methods well known in the art. These peptides can be linked to a carrier, for example, keyhole limpet hemocyanin, to increase the immunogenicity and the production of antibodies to the immunogen.
[0031] The present invention will now be illustrated by reference to the following examples which set forth particularly advantageous embodiments. However, it should be noted that these embodiments are illustrative and are not to be construed as restricting the invention in any way.
BRIEF DESCRIPTION OF THE FIGURES
[0032] [0032]FIG. 1 shows a schematic drawing of the first step in the diabody construction, exchange of the V-regions.
[0033] [0033]FIG. 2 shows a schematic drawing of the exchange of the linker, the second step in the diabody construction.
[0034] [0034]FIG. 3 shows a schematic drawing of the strategy applied for cloning of the anti-CD40/anti-CD86 diabody.
[0035] [0035]FIG. 4 shows a BIAcore sensogram showing the capability of the diabody to bind the CD86-Ig and CD40-Ig antigen simultaneously. From the periplasmic fraction, injected at t=l110 (sec) on a surface containing 6537 Response Units (RU) CD86-Ig, 1300 RU diabody was captured at t=230 (see), as can be seen by the difference in response after the first wash and the normalized signal before injection. At t=360 (sec) CD40-Ig was injected during 120 sec. The diabody, arrested with one binding domain to the CD86-Ig, reacted with the other domain to CD40-Ig yielding 550 RU captured antigen (difference in signal between the second wash at t=480 (sec) and before the second injection at t=360 (sec)).
[0036] [0036]FIG. 5 shows the results of a T cell activation experiments in which T cells are stimulated with allogeneic monocytes. T cell activation is partially inhibited by blocking CD80 and CD86 with CTLA4-Ig or an antagonistic anti-CD40 monoclonal antibody M3 alone, but almost completely blocked when CTLA4-Ig and antagonistic anti-CD40 monoclonal antibody M3 are combined.
[0037] [0037]FIG. 6 shows the results of a T cell restimulation experiments in which T cells are stimulated with allogeneic monocytes in the presence of blocking agents during primary stimulation and analysed for proliferative capacity during restimulation in the absence of blocking agents. The presence of CTLA4-Ig alone only results in a slight alloantigen-specific hypo-responsiveness, whereas the combination of CTLA4-Ig with CsA or the antagonistic anti-CD40 monoclonal antibody M3 results in T cell unresponsiveness. T cell responses to the control third-party alloantigen-expressing monocytes is not affected. Closed bars are the T cell responses to the alloantigen used in the primary culture, open bars represent T cell responses to third-party alloantigen-expressing monocytes.
[0038] [0038]FIG. 7 shows the results of a T cell restimulation experiments in which T cells are stimulated with allogeneic PBMC in the presence of blocking agents during primary stimulation and analysed for proliferative capacity during restimulation in the absence of blocking agents. The presence of antagonistic monoclonal antibody to CD40 and antagonistic monoclonal antibody to CD86, with or without antagonistic monoclonal antibody to CD80 results in alloantigen-specific T cell unresponsiveness. The presence of antagonistic monoclonal antibody to CD40 alone or in combination with antagonistic monoclonal antibody to CD80 only results in partial inactivation of the T cells.
Examples
[0039] Materials and Methods:
[0040] p-CD40 and CD86 extracellular domain Ig fusion proteins
[0041] In several experiments fusion proteins of lymphocyte cell surface receptors and the Fc-region of human IgG were used. These extracellular domain (ED) fusion proteins (ED-Ig fusion proteins) have been generated by fusion of the nucleic acid sequence encoding the extracellular domain of the cell surface receptors generated by PCR amplification based on published cDNA sequences to the CH1/hinge-CH3 region (Fc) of human IgG1 based on the sequence by Ellison et al. ( NAR 10:4071 (1982)). ED-Ig fusion proteins were expressed in Sf9 insect cells and were used as conditioned medium or after purification by affinity chromatography using protein A.
[0042] Cell lines and culture conditions
[0043] The B-cell line JY was cultured in T75 culture flasks routinely (Costar, Cambridge, Mass., U.S.A.) in Iscove's modified Dulbecco's medium (IMDM) to which 50 μg/ml gentamycin and 10% foetal calf serum was added (FCS) (Hyclone, Logan, Utah U.S.A.). The cells were cultured in a humidified incubator at 37° C. and 5% CO 2 . Every week the cells were split ({fraction (1/20)} to {fraction (1/100)}). To store the cell line, ampoules were made containing 5-10×10 6 cells/ml Hank's balanced salt solution HBSS supplemented with 20% FCS and 10% DMSO and stored in the liquid nitrogen.
[0044] Lymphocyte isolation and stimulation
[0045] Peripheral blood mononuclear cells (PBMC) were isolated from heparinized blood from healthy donors by Ficoll-Hypaque density centrifugation and re-suspended in complete medium consisting of RPMI 1640 (Gibco, Paisley, UK) supplemented with 2 mM L-Glutamine, streptomycin (100 mg/ml), penicillin (100 U/ml) and 5% heat-inactivated autologous plasma. Enriched monocyte preparations were prepared by rosetting of PBMC with AET-treated sheep red blood cells and removal of E-rosetting cells on Ficoll-Hypaque density gradients, followed by cold aggregation of monocytes as essentially described by Zupo et al. ( Eur. J. Immunol. 21:351 (1991)). T cells were further purified from the PBMC preparations by depletion of monocytes, B cells and NK cells using Lympho-Kwik T (One Lambda, Los Angeles, Calif., U.S.A.) according to the manufacturers protocol.
[0046] For primary mixed lymphocyte cultures with enriched monocytes and purified T cells, 0.5-1×10 6 /ml purified T cells and 0.1-0.2×10 6 /ml monocytes were cultured in 200 ml complete culture medium in 96-well plates for 6 days in the presence or absence of blocking agents in concentrations ranging from 1-10 μg/ml. For the last 8 hours of the culture period, cells were pulsed with 1 mCi [3H]-thymidine (Amersham International, Amersham, UK). Cells were harvested on glass fiber filters by using a Skatron automatic cell harvester, and radioactivity on the paper was counted in a liquid scintillation counter. For re-stimulation experiments, the T cells (0.5-1×10 6 /ml) and monocytes from the same donor (0.1 to 0.2×10 6 /ml) were cultured for 6 days in 1 ml complete medium in 24-well plates in the presence or absence of blocking agents in concentrations ranging from 1-10 μg/ml and in the presence or absence of cyclosporin A (CsA) at a concentration of 400 ng/ml. After 6 days, the remaining cells were collected and cultured for an additional 2 days, before re-stimulation for 3 days in the absence of blocking agents. T cell proliferation was determined as described above for primary mixed lymphocyte cultures.
[0047] Mixed lymphocyte cultures were also performed with non-separated PBMC. In these experiments, fresh PBMC (1×10 6 /ml) as responder cells and PBMC that were pre-activated with human IL-4(20 μg/ml) and human GM-CSF (100 U/ml) (0.1×10 6 /ml) as stimulator cells were cultured for 6 days in 1 ml complete culture medium in 24-well plates in the presence or absence of blocking agents in concentrations ranging from 1-10 μg/ml. After 6 days the remaining cells were collected and cultured for an additional 3 days, before the allo-reactive T cells were re-stimulated with the same PBMC that were pre-activated with human IL-4 (20 μg/ml) and human GM-CSF (100 U/ml) (0.1×10 6 /ml) as stimulator cells for 3 days in the absence of blocking agents. T cell proliferation was assayed by [3H]-thymidine incorporation as described above.
[0048] Polymerase chain reaction
[0049] To amplify DNA fragments, polymerase chain reactions (PCR) were performed. A typical PCR reaction mix contained: 0-10 mM MgCl 2 , 50 mM KCl, 10 mM Tris-HCl pH 9.0, 1.0% Triton X-100, 0.25 mM dNTP each, 25 pmol primer/100 μl reactions mix, 1-1000 ng DNA/100 μl reaction mix and 2.5 U Taq polymerase. Reactions were run using a Perkin Elmer thermocycler (Perkin Elmer Corp, Norwalk Conn.). A stantard PCR scheme consisted of one step for 2-5 min at 95° C. to denature the DNA, followed by 20-40 cycles of 1 min at 95° C., 1 min at 55° C. and 1-4 min at 72° C. After the final step an extension step was performed for 7 min at 72° C.
[0050] Flow cytometric analysis (FACS)
[0051] Cells (0.1-0.2×10 6 /sample) were incubated for 20 min at 4° C. with the specific monoclonal antibody (0.1-1 mg/sample). After washing with FACS buffer (PBS pH 7.4 1% BSA 0.1% NaN 3 ), the cells were incubated for another 20 min at 4° C. with goat anti-mouse antibodies conjugated to fluorescein isothiocyanate (FITC) or phycoerythin (PE). The cells were washed with FACS buffer and finally suspended in FACS buffer containing 0.5% paraformaldehyde and analysed with a FACScan flow cytometer (Becton Dickinson). The specific binding of the monoclonal antibodies is expressed as the mean fluorescent intensity in arbitrary units. A similar protocol was used to test the single chain antibody expressing phage particles. In this case detection was done by using an un-conjugated sheep anti-M13 antibody (Pharmacia AB, Uppsala Sweden), followed after washing by incubation with donkey anti-sheep conjugated to FITC (Sigma Chemical Co. St. Louis, Mo., U.S.A.). Likewise a similar protocol was used to demonstrate the biological activity of the diabody and triabody constructs. In these experiments detection was done by incubation of the cells with the diabody or triabody constructs followed by incubation with one of the ED-Ig fusion proteins, followed by incubation with an FITC-conjugated anti-human IgG antiserum.
[0052] SDS-PAGE and Western blotting analysis
[0053] To analyse the expressed constructs SDS-PAGE and Western blot analysis was performed. Briefly, samples were boiled for 5 min in 0.8% sodium dodecyl sulfate (SDS) and 1 mM dithiothreitol (DTT). Subsequently the samples were run on a 15% SDS-polyacrylamide gel electrophoresis (SDS-PAGE; 2 h 100 V). After electrophoresis the gel was electroblotted to a nitrocellulose filter or stained with 0.1% coommassie blue in 10% methanol and 10% acetic acid. Electroblotting was done in 25 mM Tris-HCl, 192 mM glycine and 10% methanol pH 8.3 for 1 h at 100 V; 4° C. After blotting the nitrocellulose filter was blocked with 1% BSA in PBS-Tween (0.05%) for 1 hour at room temperature. Subsequently the blot was incubated at room temperature in PBS-Tween with a anti c-myc antibody for detection. After incubation with a second antibody (peroxidase labelled), the blots were stained by 4-chloro-naphtol.
[0054] BIACore analysis
[0055] Analysis were performed on the Pharnacia Biosensor 2000. The CM chip was activated with 0.2 M EDC/0.05 M NHS for 5 min. Subsequently coupling of ligand was done in 10 mM NaAc pH5.0 during 5 min (0.1 mg Ig construct/ml). This was followed by loading of the ScFv, Mab or dia/triabody constructs in various concentrations in PBS buffer. In case of the dia/triabody constructs the chip was washed followed by loading of the second Ig construct. The sensor surface was regenerated with 0.1 M NaOH.
Example 1
[0056] Single chain antibody fragments expressing phage from monoclonal antibodies to human CD40 and CD86 were generated as follows. For the generation of a single chain antibody fragment (ScFv) of the anti-CD40 monoclonal antibody 5D12 both the VH and VL region were amplified by PCR, followed by a second assembly PCR to connect both regions. For this purpose 4 primers were designed (SEQ ID NO: 1-4). SEQ ID NO: 1 contains a HindIII and SfiI restriction site for cloning purposes followed by a degenerated sequence annealing to the 5′ VH region of 5D12. SEQ ID NO: 2 contains a degenerate sequence for the 3′ part of the VH region followed by a sequence encoding a ((Gly) 4 Ser) 3 linker and the 5′ part of the VL regions. SEQ ID NO: 3 is a degenerated primer having homology with the 5′ part of the VL region, while the last primer (SEQ ID NO: 4) contains a NotI restriction site and anneals to the 3′ part of the VL region. Briefly, these primers were used to separately PCR amplify the VH and VL regions of monoclonal antibody 5D12. As template for this PCR reaction we used a plasmid containing the VH or VL regions of 5D12 (VH: SEQ ID NO: 5 and VL: SEQ ID NO: 6). The cDNA obtained in this PCR step was gel purified and used in an assembly PCR resulting in the linkage of the V region through the (Gly 4 Ser) 3 linker. Subsequently the obtained single chain 5D12 construct was digested with the restriction enzymes HindHIII and NotI, followed by ligation in pGEM-13Zf (Promega Madison U.S.A.). The ligation was transformed in DH5α and plated on LB plates. By sequencing of several clones, a correct 5D12 ScFv clone was found (SEQ ID NO: 7).
[0057] For the generation of ScFv's reactive with human CD86, the same primer set as for 5D12 was used. All the steps in the generation of the ScFv of the anti-CD86 monoclonal antibody Fun-1 were performed as described above for the 5D12 ScFv reactive with human CD40. The V regions of Fun-1 (VH: SEQ ID NO: 8; VL: SEQ ID NO: 9) were used as template to obtain the anti-CD86 ScFv construct (SEQ ID NO: 10).
Example 2
[0058] Construction of bi-specific diabody molecules capable of binding to human CD40 and human CD 86:
[0059] Bi-specific bivalent molecules were generated by shortening the flexible linker sequence in the anti-CD40 ScFv and in the anti-CD86 ScFv, from fifteen residues to five (Gly 4 Ser) and by cross-pairing the variable heavy and light chain domains from the two single chain Fv fragments with the different antigen recognition. The construction was performed in three steps. The light chain variable fragments were exchanged in the ScFv constructs from anti-CD86 (aCD86) and anti-CD40 (aCD40) by using restriction enzyme sites located in the 5′ end (SacI at nucleotide numbers 7 to 12 of VL) and just outside the 3′ part of the light chain variable gene (Notl) (see FIG. 1). In the following step the 15-residue linker of the chimeric constructs VH-aCD86/15AA-linker/VL-CD40 (coded 7.2/15/40) and VH-aCD40/15AA-linker/VL-aCD86 (coded 40/15/7.2) was replaced by the 5 residue linker (Gly4Ser) by using sites located in the 3′ part of VH (Bsu361 at nucleotide number 335 of the anti-CD40 VH or at 371 of the anti-CD86 VH to number +2 in the linker sequence) and the 5′ part of VL end (Sacl at nucleotide number 7 to 12 both VL's) (see FIG. 2). Finally, both chimeric cassettes were combined in the vector pUC 119-fabsol (a pUC 119 derivative similar to pUC 119His6mycXba (Low et al., J. Mol. Biol. 260:359 (1996)), but with all Apall-sites in the vector backbone deleted by in vitro mutagenesis) containing a bi-cistronic expression cassette. The subcloning was performed in two steps. First, the aCD86/5 AA-linker/aCD40-construct was cloned in pUC119-fabsol using the restriction sites SfiI and NotI. Subsequently the ScFv cassette of aCD40/5 AA-linker/aCD86 was amplified with the following oligonucleotide primers: 5′-TCT CAC AGT GCA CAG GTG CAG CTG CAG GAG TCT GG-3′ (SEQ ID NO: 11) and 5′-CGT GAG AAC ATA TGG CGC GCC TTA TTA CCG TTT GAT TTC CAG GTT GGT GCC-3′ (SEQ ID NO: 12). These primers contain an ApaLI-and an AscI-site respectively (underlined). The amplified PCR-fragment was digested with ApaLI and AscI, and ligated in the pUC119-fabsol plasmid containing the aCD86/5AA-linker/aCD40-construct. A diabody-producing clone containing both ScFv cassettes was identified and used for expression of the recombinant diabody molecule (pUC119-fabsol-CD40/CD86) (5D12VH+FUNVL: SEQ ID NO: 13; FUNVH+5D12VL: SEQ ID NO: 22).
[0060] The whole cloning strategy to obtain the bi-specific diabody molecule based on antagonistic anti-CD40 Mabs and antagonistic anti-CD86 Mab Fun-1, capable of binding to human CD40 and human CD86 molecule on antigen presenting cells, is summarized in FIG. 3. The same procedure is also used for the generation of a bi-specific diabody molecule based on antagonistic anti-CD40 Mabs and antagonistic Mabs reactive with both CD80 and CD86, capable of binding to human CD40, human CD80 and human CD86 molecule on antigen presenting cells.
Example 3
[0061] Expression, isolation and characterization of bi-specific diabody molecules capable of binding to human CD40 and human CD86:
[0062] For the production of the bi-specific diabody molecule capable of binding to human CD40 and human CD86, the plasmid containing the aCD86/aCD40-bicistronic expression cassette described in Example 2 above was used. Fifty ml of 2YT medium (100 μg/ml amp, 0.1% glucose) was inoculated (1 v/v %) with a saturated culture (16 hours grown at 30° C.). After 5 hours growth at 30° C. and with a culture having an optical density at 600 nm of 0.9, the diabody production was induced by adding IPTG to a concentration of 1 mM. Cultivation was continued for 4 hours at 20° C. and the cells from 15 ml culture were pelleted (10 minutes at 1100 g at room temperature). Supernatant and cells were stored at −20° C. until further processed. The remaining 35 ml culture was grown at 20° C. for another 16 hours. Cells were pelleted as described above. Periplasmic fractions were prepared by resuspending the cells in 0.53 ml cold TES-buffer (20 mM Tris-HCl; 0.5 mM EDTA; 0.5 M sucrose pH 8.0). The mixture was incubated for 2 minutes on ice, subsequently 0.59 ml cold three fold diluted TES was added and the incubation was prolonged for 30 minutes. The spheroplasts were centrifuged for 15 minutes at 1100 g at 4° C. and the supernatant containing the periplasmic proteins was collected. The pellet fraction was resuspended in 0.75 ml TES/MgSO 4 (TES-buffer; 15 mM MgSO 4 ) and incubated for 30 minutes on ice. Spheroplasts were pelleted for 15 minutes at 1100 g at 40° C. and the supernatant added to the first supernatant fraction. The total periplasmic fraction was cleared again (15 minutes at 1100 g at 4° C.) and dialyzed against PBS. All fractions were analyzed on PAGE and Western blot with the anti-c-myc antibody for detection. The highest concentration of ScFv was found in the periplasmic fraction prepared from the culture after 4 hours induction, and to some degree in the medium fraction of the culture induced for 20 hours. The functionality of the produced diabody was tested in BIAcore. Purified CD86-Ig was immobilized on the surface of a CM-hip, yielding 6500 RU (Response Units) of coupled protein. Injection of the periplasmic fraction for 120 sec with a flow rate of 10 μl/min resulted in the capture of approx. 1200 RU diabody. Subsequently CD40-Ig was injected under the same conditions as the diabody resulting in the binding of an additional 540 RU antigen. This experiment demonstrated the capability of the produced diabody molecule to bind CD40 and CD86 simultaneously (see FIG. 4).
Example 4
[0063] Construction of bi-specific and tri-specific triabody molecules capable of binding to human CD40 and CD86 or human CD40, CD80and CD86:
[0064] The construction of bi-specific and tri-specific triabody molecules is analogous to the scheme described above for the diabody, except that the linker has to be deleted (zero residue linker). This is accomplished by in vitro mutagenesis, using single stranded phagemid DNA and oligonucleotides encoding the mutation. Using ScFv constructs of antagonistic monoclonal antibodies to human CD40, CD80 and CD86 at least two gene constructs are possible: (i) VHαCD40/0/VLαCD80-VHαCD80/0/VLαCD86-VHαCD86/0/VLαCD40 and; (ii) VHαCD40/0/VLαCD86-VHαCD86/0/VLαCD80-VHαCD80/0/VLαCD40. All VH/VL-combinations are made by exchanging VH- and VL-domains in the constructs such as described above for bi-specific diabodies having the 5 amino acid linkers, applying the strategy described above using SfiI and Bsu36I to exchange VH regions, and SacI and NotI to exchange VL regions. Subsequently, the three ScFv-cassettes are cloned in a single expression module encoding a tricistronic mRNA. This DNA will serve as template for an oligo-directed in vitro mutagenesis procedure, to delete the 5 residue linker in one up to three VH-VL-pairs. The various triabodies that are made, may differ in binding characteristics due to other orientations of the ScFv domains and in linker length. Only one of the three ScFv cassettes is provided with the previously mentioned tag sequences. In order to drive triabody formation as well as to maintain stability, disulfide bridges can be introduced by adding cysteine residues at the carboxyterminus or within the V-regions.
Example 5
[0065] Construction of a fusion molecule consisting of an antagonistic anti-CD40 monoclonal antibody linked by its C-terminal residue to the extracellular domain of human CTLA4 capable of binding to CD40, CD80 and CD86 can be carried out as follows. The conceptual therapeutic agent is a fusion protein combining the high affinity and specificity of CTLA4 for both CD80 and CD86 with an antagonistic anti-CD40 monoclonal antibody. This fusion molecule is produced in stable, active form as a complete anti-CD40 monoclonal antibody to which the extracellular domain of human CTLA4 (CTLA4ED) is C-terminal linked by a flexible linker. The construction of the anti-CD40 antibody attached by its Fc part to the extracellular domain of CTLA4 is done by the following PCR and cloning steps. The VH and CH1 regions of anti-CD40 together with a leader sequence are amplified using the oligonucleotides 5′ GCG CGA ATT CAT GGA CAT GAG GGT CCC CGC 3′ (SEQ ID NO: 14) and 5′ AGA TTT GGG CTC AAC TTT CTT GTC CAC 3′ (SEQ ID NO: 15). This is followed by amplification of the CH2 and CH3 regions of human IgG using the oligonucleotides 5′ GTG GAC AAG AAA GTT GAG CCC AAA TCT 3′ (SEQ ID NO: 16) and 5′ GCGC GAA TTC TTA AGC GGC CGC AGA TCC GCC GCC ACC CGA CCC ACC TCC GCC CGA GCC ACC GCC ACC TTT ACC CGG AGA CAG 3′ (SEQ ID NO: 17). After removing of the primers a second PCR is done to assemble both PCR products to obtain a full-length 5D12 heavy chain. The obtained PCR product is gel purified and cloned in pCR Script using the Stratagene cloning kit. Briefly, the PCR product is incubated with plasmid together with T4 ligase and SrfI for 1 h at room temperature, after which the entire sample is transformed in Xl1Blue E. coli cells. The cells are plated on LB plates containing 100 μg ampiciline/ml, 20 μg IPTG/ ml and 20 μg Xgal/ml. After incubation o/n at 37° C. putative white clones are analyzed for having an insert. Clones containing inserts are analyzed by cycle sequencing using M13 and M13 reverse primers. After confirming the correct sequence, the anti-CD40 heavy chain is cloned using the EcoRI restriction site in the bicistronic baculovirus expression plasmid pAcUW51 (Pharmingen) after the p10 promoter. The in this way obtained construct already contains C-terminal a flexible (Gly 4 Ser) 3 linker after which the CTLA4ED part was cloned. Therefore the CTLA4ED part is amplified with the oligonucleotides 5′ GCGC GCG GCC GCA ATG CAC GTG GCC CAG CCT G 3′ (SEQ ID NO: 18) and 5′ GCGC GCG GCC GC CTA GTC AGA ATC TGG GCA CGG TTC 3′ (SEQ ID NO: 19) by PCR, gel purified and cloned after the heavy chain of 5D12 using the NotI cloning site. After confirmation by sequence analysis of this step the light chain is cloned. This is done by using a plasmid which already contained the VL region of 5D12 attached to a human CL region. So using the oligonucleotides 5′ GCGC GGATCC ATG GAC ATG AGG GTC CCC GC 3′ (SEQ ID NO: 20) and 5′ GCGC GGATCC CTA ACA CTC TCC CCT GTT GAA GC 3′ (SEQ ID NO: 21) the light chain of 5D12 is amplified and cloned in the constructed pAcUW51 expression plasmid using the BamHI cloning site after the polyhedrin promoter. After DNA sequence analysis a correct clone is obtained. After this confirmation, the expression plasmid containing the 5D12 CTLA4ED construct is introduced into Sf9 insect cells along with the viral AcNPV wild-type DNA using the BaculoGold transfection system of Pharmingen. Recombinant virus is plaque-purified and the integrity of the expression cassette is checked by PCR and cycle sequencing. For protein production, insect cells are used. These cells can grow in suspension in serum-free medium, and are the best known secretors of heterologous proteins. The fusion protein is purified from serum-free conditioned medium by S. aureus protein A affinity chromatography (Harlow and Lane, 1988). Purity is checked by SDS-PAGE and by western blotting under reducing and non-reducing conditions to assess the extent of dimerization.
Example 6
[0066] Effects of blocking the CD4L-CD40 and/or CD80/86-CD28 pathway on the activation of T cells:
[0067] It has been demonstrated extensively that blocking the CD80/86 pathway results in an inhibition of activation of T cells (reviewed in Van Gool et al., Res. in Immunol. 146:183 (1995)). However, under a number circumstances, blocking of the CD80/86 interaction does not result in complete prevention of T cell activation. This is exemplified by FIG. 5, in which purified human T cells are stimulated with allogeneic monocytes as detailed above under materials and methods. Addition of CTLA4-Ig (blocking both CD80 and CD86) only resulted in a partial inhibition of the alloantigen-specific T cells. Surprisingly, addition of the antagonistic anti-CD40 monoclonal antibody M3 also resulted in a partial inhibition of T cell activation to the same extend as CTLA4-Ig. Even more surprisingly, the combination of the antagonistic anti-CD40 monoclonal antibody M3 with CTLA4-Ig resulted in nearly complete blockade of T cell activation.
[0068] It has also been demonstrated that a blockade of CD80/86 in combination with CsA results in antigen-specific T cell unresponsiveness (reviewed in Van Gool et al., Res. in Immunol. 146:183 (1995)). This has been demonstrated in mixed lymphocyte cultures, in which blocking agents were added during a primary stimulation with the alloantigen, followed by a short rest period and subsequent restimulation with the same alloantigen in the absence of blocking agents. FIG. 6 indeed shows that addition of CTLA4-Ig plus CsA, but not CTLA4-Ig alone to purified human T cells that are stimulated with allogeneic monocytes results in alloantigen-specific T cell unresponsiveness (solid bars). The response to unrelated third party alloantigen-expressing monocytes in unchanged (open bars). FIG. 6 also shows that the addition of CTLA4-Ig plus anti-CD40 monoclonal antibody M3 alone to purified human T cells that are stimulated with allogeneic monocytes also results in alloantigen-specific T cell unresponsiveness (solid bars). Again, this unresponsiveness to the alloantigen of the first culture is specific, since the response to unrelated third party alloantigen-expressing monocytes in unchanged (open bars).
[0069] In another set of experiments (FIG. 7) it is shown that a combination of blocking CD40 with the antagonistic anti-CD40 monoclonal antibody 5D12 and blocking of CD80 and CD86 with antagonistic monoclonal antibodies, results in alloantigen-specific T cell unresponsiveness when tested in MLC experiments using PBMCs as detailed above in the materials and methods section. Surprisingly, alloantigen-specific T cell unresponsiveness was also induced when the anti-CD40 monoclonal antibody was combined with the antagonistic anti-CD86 monoclonal antibody without blocking the CD80 costimulatory receptor. In contrast, the combination of the anti-CD40 monoclonal antibody and the anti-CD80 monoclonal antibody, without blocking the CD86 receptor resulted only in T cell hypo-responsiveness to the same level as with the antagonistic anti-CD40 monoclonal antibody alone. This was surprising, since it has extensively been demonstrated that blocking of both CD80 and CD86 always results in more complete inhibition that with either alone. This demonstrates that blocking the CD86-CD28 costimulatory interaction together with blocking the CD40L-CD40 costimulatory interaction with one therapeutic molecule such as described in the above examples has a strong potential for immunotherapy of T cell mediated diseases.
Example 7
[0070] Gene Therapy to Produce the Proteins of the Invention
[0071] Another embodiment of the invention includes gene constructs that direct the expression in vivo of the diabodies of the invention which bind to the human CD40 and CD86 antigens (or the diabodies or triabodies which bind to human CD40, CD80 and CD86, or the fusion protein including anti-CD40 and CTLA4-Ig) located on the surface of antigen presenting cells. The gene constructs can be introduced by well-known methods using viral vectors, including a retrovirus, an adenovirus, a parvovirus or any other vector permitting cellular transfer of the gene constructs, or by incorporation of the gene construct into liposomes with or without the viral vector. The gene constructs can also be transfected into cells ex vivo, using known methods including electroporation, calcium phosphate transfection, micro-injection, or incorporation of the gene constructs into liposomes followed by transfection. The cells are then introduced into the patient for antibody expression in vivo.
[0072] The gene constructs are made by the cloning strategy as set forth above for construction of the diabodies and triabodies of the invention. The heavy and light chain genes can be placed in one plasmid construct either under separate promoter control or under one promoter in a dicistronic arrangement. The antibody gene fragments can also be placed under control of promoters that allow the turning on and off of the gene expression with appropriate exogeneous factors such as steroids or metal ions.
[0073] These gene constructs can be prepared as plasmids for direct DNA delivery into host cells or tissues. With additional manipulations using techniques known in the field of genetic therapy, the gene constructs can also be coupled with a suitable viral particle, including a retrovirus, an adenovirus, or a parvovirus which allow gene delivery through viral infection. Any of these gene constructs can also be used to transfect cells suitable for antibody expression ex vivo. Following transfection, the cells are introduced into the subject where the antibody is expressed.
[0074] To test whether these gene constructs can direct the expression of the desired antibody or antibody fragments, suitable gene constructs or viral particles are first used to transfect or infect appropriate host cells. Culture supernatants of the transfected/infected cells are collected an appropriate period post transfection/transfection and tested for antibody expression in ELISA to detect the presence of the antibody and its ability to bind CD40 and CD86, or CD40, CD80 and CD86, if applicable. Further testing can include the measurement of the antibody affinity and the ability to compete with the parent antibodies for binding to the antigens.
[0075] To test whether the gene constructs or the cells transfected/infected as above can direct the antibody expression in vivo, plasmid gene constructs (or the transfected/infected cells) can be administered to BALB/c mice intramuscularly, either formulated with phosphate buffered saline or with suitable liposome preparation, or in the case of viral vectors, using proper infection protocols. The treated animals are analyzed for expression of the diabodies, triabodies or fusion proteins, as applicable, either with tissue section staining, or by expression thereof in blood.
1
22
1
52
DNA
human
1
gcgcaggctt ggcccagccg gccatggccc aggtsmarct gcagsagtct gg 52
2
89
DNA
human
2
gtgagctcga tgtccgatcc gccaccgcca gagccacctc cgcctgaacc gcctccacct 60
gaggagacgg tgaccgtggt cccttggcc 89
3
24
DNA
Artificial Sequence
human
3
gacatcgagc tcacycagtc tcca 24
4
42
DNA
human
4
gcgcgcggcc gcccgtttka tttccagstt ggtgcctcca cc 42
5
339
DNA
human
5
caggtgcaac tcgtggagtc tggacctggc ctggtgaaac cctcacagag cctgtccatc 60
acatgcactg tctctgggtt ctcattatcc agatatagtg tatactgggt tcgccagcct 120
ccaggaaagg gtctggagtg gctgggaatg atgtggggtg gtggatccac agactataat 180
tcagctctca aatccagact gaccatcagc aaggacacct cgaagaacca ggtcttctta 240
aaaatgaaca gtctgcgagc tgaggacaca gccatgtact actgtgtcag aaccgatggg 300
gactactggg gtcaaggaac caccgtcacc gtctcctca 339
6
339
DNA
human
6
gacctccagc tgacccagtc tccactctcc ctgcctgtca gtcttggaga tcgagcctcc 60
atctcttgca gatctagtca gagccttgta aacagtaatg gaaacaccta tttacattgg 120
tacctgcaga agccaggcca gtctccaaag ctcctgatct acaaagtttc caaccgattt 180
tctggggtcc cagacaggtt cagtggcagt ggatcaggga cagatttcac actcaagatt 240
agcagagtgg aggctgagga tgtgggagtt tattactgct ctcaaagtac acatgttccg 300
tggacgttcg gtggaggcac caagctggaa atcaaacga 339
7
723
DNA
human
7
caggtgcagc tgcaggagtc tggacctggc ctggtgaaac cctcacagag cctgtccatc 60
acatgcactg tctctgggtt ctcattatcc agatatagtg tatactgggt tcgccagcct 120
ccaggaaagg gtctggagtg gctgggaatg atgtggggtg gtggatccac agactataat 180
tcagctctca aatccagact gaccatcagc aaggacacct cgaagaacca ggtcttctta 240
aaaatgaaca gtctgcgagc tgaggacaca gccatgtact actgtgtcag aaccgatggg 300
gactactggg gccaagggac cacggtcacc gtctcctcag gtggaggcgg ttcaggcgga 360
ggtggctctg gcggtggcgg atcggacatc gagctcactc agtctccact ctccctgcct 420
gtcagtcttg gagatcgagc ctccatctct tgcagatcta gtcagagcct tgtaaacagt 480
aatggaaaca cctatttaca ttggtacctg cagaagccag gccagtctcc aaagctcctg 540
atctacaaag tttccaaccg attttctggg gtcccagaca ggttcagtgg cagtggatca 600
gggacagatt tcacactcaa gattagcaga gtggaggctg aggatgtggg agtttattac 660
tgctctcaaa gtacacatgt tccgtggacg ttcggtggag gcaccaagct ggaaataaaa 720
cgg 723
8
375
DNA
human
8
gaggtccaac tgcagcagtc tggacctgag ctggagaagc ctggcgcttc agtgaagata 60
tcctgcaagg cttctggtta ctcattcact gactacaaca tgaactgggt gaagcagagc 120
aatggaaaga gccttgagtg gattggaaat attgatcctt actatggtgg tactagttac 180
aatcagaagt tcaagggcaa ggccacattg actgtagaca aatcctccag cacagcctac 240
atgcagctca acagcctgac atctgaagac tctgcagtct atttctgtgc aagatgggac 300
tataggtacg acgacgggag ggcttactat gttatggact tctggggtca aggaacctca 360
gtcaccgtct cctca 375
9
339
DNA
human
9
gagctccaga tgacccagtc tccatcatct ctggctgcgt ctgcaggaga aaaggtcact 60
atgagctgta agtccagtca aagtgtttta tacagttcaa atcagaagaa ctacttggcc 120
tggtaccagc agaaaccagg gcagtctcct aaactgctga tctactgggc atccactagg 180
gaatctggtg tccctgatcg cttcacaggc agtggatctg ggacacattt tactctgacc 240
gtcagcagtg tgcaagctga agacctggca gtttattact gtcatcaata cctctactcg 300
tggacgttcg gtggaggcac caacctggaa atcaaacgg 339
10
759
DNA
human
10
caggtccaac tgcagcagtc tggacctgag ctggagaagc ctggcgcttc agtgaagata 60
tcctgcaagg cttctggtta ctcattcact gactacaaca tgaactgggt gaagcagagc 120
aatggaaaga gccttgagtg gattggaaat attgatcctt actatggtgg tactagttac 180
aatcagaagt tcaagggcaa ggccacattg actgtagaca aatcctccag cacagcctac 240
atgcagctca acagcctgac atctgaagac tctgcagtct atttctgtgc aagatgggac 300
tataggtacg acgacgggag ggcttactat gttatggact tctggggcca agggaccacg 360
gtcaccgtct cctcaggtgg aggcggttca ggcggaggtg gctctggcgg tggcggatcg 420
gacatcgagc tcacccagtc tccatcatct ctggctgcgt ctgcaggaga aaaggtcact 480
atgagctgta agtccagtca aagtgtttta tacagttcaa atcagaagaa ctacttggcc 540
tggtaccagc agaaaccagg gcagtctcct aaactgctga tctactgggc atccactagg 600
gaatctggtg tccctgatcg cttcacaggc agtggatctg ggacacattt tactctgacc 660
gtcagcagtg tgcaagctga agacctggca gtttattact gtcatcaata cctctactcg 720
tggacgttcg gtggaggcac caacctggaa atcaaacgg 759
11
35
DNA
human
11
tctcacagtg cacaggtgca gctgcaggag tctgg 35
12
51
DNA
human
12
cgtgagaaca tatggcgcgc cttattaccg tttgatttcc aggttggtgc c 51
13
764
DNA
human
13
gtgaaaaaat tattattcgc aattccttta gttgttcctt tctattctca cagtgcacag 60
gtgcagctgc aggagtctgg acctggcctg gtgaaaccct cacagagcct gtccatcaca 120
tgcactgtct ctgggttctc attatccaga tatagtgtat actgggttcg ccagcctcca 180
ggaaagggtc tggagtggct gggaatgatg tggggtggtg gatccacaga ctataattca 240
gctctcaaat ccagactgac catcagcaag gacacctcga agaaccaggt cttcttaaaa 300
atgaacagtc tgcgagctga ggacacagcc atgtactact gtgtcagaac cgatggggac 360
tactggggcc aagggaccac ggtcaccgtc tcctcaggtg gaggcggttc agacattgag 420
ctcacccagt ctccatcatc tctggctgcg tctgcaggag aaaaggtcac tatgagctgt 480
aagtccagtc aaagtgtttt atacagttca aatcagaaga actacttggc ctggtaccag 540
cagaaaccag ggcagtctcc taaactgctg atctactggg catccactag ggaatctggt 600
gtccctgatc gcttcacagg cagtggatct gggacacatt ttactctgac cgtcagcagt 660
gtgcaagctg aagacctggc agtttattac tgtcatcaat acctctactc gtggacgttc 720
ggtggaggca ccaacctgga aatcaaacgg taataaggcg cgcc 764
14
30
DNA
human
14
gcgcgaattc atggacatga gggtccccgc 30
15
27
DNA
human
15
agatttgggc tcaactttct tgtccac 27
16
27
DNA
human
16
gtggacaaga aagttgagcc caaatct 27
17
82
DNA
human
17
gcgcgaattc ttaagcggcc gcagatccgc cgccacccga cccacctccg cccgagccac 60
cgccaccttt acccggagac ag 82
18
31
DNA
human
18
gcgcgcggcc gcaatgcacg tggcccagct t 31
19
36
DNA
human
19
gcgcgcggcc gcctagtcag aatctgggca cggttc 36
20
31
DNA
human
20
gcggcggatc catggacatg agggtccccg c 31
21
33
DNA
human
21
gcgcggatcc ctaacactct cccctgttga agc 33
22
879
DNA
human
22
atgaaatacc tattgcctac ggcagccgct ggattgttat tactcgcggc ccagccggcc 60
atggcccagg tccaactgca gcagtctgga cctgagctgg agaagcctgg cgcttcagtg 120
aagatatcct gcaaggcttc tggttactca ttcactgact acaacatgaa ctgggtgaag 180
cagagcaatg gaaagagcct tgagtggatt ggaaatattg atccttacta tggtggtact 240
agttacaatc agaagttcaa gggcaaggcc acattgactg tagacaaatc ctccagcaca 300
gcctacatgc agctcaacag cctgacatct gaagactctg cagtctattt ctgtgcaaga 360
tgggactata ggtacgacga cgggagggct tactatgtta tggacttctg gggccaaggg 420
accacggtca ccgtctcctc aggcggtggc ggatcggaca ttgagctcac tcagtctcca 480
ctctccctgc ctgtcagtct tggagatcga gcctccatct cttgcagatc tagtcagagc 540
cttgtaaaca gtaatggaaa cacctattta cattggtacc tgcagaagcc aggccagtct 600
ccaaagctcc tgatctacaa agtttccaac cgattttctg gggtcccaga caggttcagt 660
ggcagtggat cagggacaga tttcacactc aagattagca gagtggaggc tgaggatgtg 720
ggagtttatt actgctctca aagtacacat gttccgtgga cgttcggtgg aggcaccaag 780
ctggaaataa aacgggcggc cgcagaacaa aaactcatct cagaagagga tctgaatggg 840
gccgcacatc accatcatca ccattaataa gaatccbct 879 | The invention provides a ligand capable of binding to the human CD40 antigen and to the human CD86 antigen, and optionally to the CD80 antigen, said antigens being located on the surface of human lymphocytes, as well as vectors capable of producing the ligand and uses of the ligand in inducing T cell tolerance. Said ligand can be an antibody, which can be a trispecific diabody capable of binding to CD40 and to both CD80 and CD86, or a bispecific diabody capable of binding to human CD40 and to human CD86, or else a trispecific triabody capable of binding to CD40, CD80 and CD86. | 0 |
FIELD OF THE INVENTION
[0001] The present inventions apply generally to improved methods of wastewater treatment in treatment facilities employing an activated sludge process. More particularly, the inventions are directed to enhancing the secondary treatment process by selected reaeration, recirculation and nitrification techniques that result in improved volumetric loading, hydraulic capacity and nutrient removal over conventional activated sludge treatment techniques.
BACKGROUND OF THE INVENTION
[0002] Wastewater generated by municipalities and industries water is commonly collected and routed to a treatment facility for the removal of a variety of physical, chemical and biological pollutants prior to being discharged into a receiving body of water. To effect the necessary treatment, many public and private treatment facilities employ both physical and biological treatment methods. Physical methods—including screening, grinding and physical settling processes—are effective for the removal of larger and heavier solids in the wastewater. However, lighter, smaller solids and other soluble pollutants in the wastewater resist removal by physical methods. For these pollutants, biological treatment methods such as activated sludge and trickling filters are commonly employed.
[0003] In the activated sludge process, settled wastewater is introduced into a reactor where an aerobic microbial culture is maintained in suspension. The culture may include a variety of different strains of bacteria, protozoa and rotifers. The combination of this microbial culture and the wastewater is commonly referred to as mixed liquor. Aeration in the reactor creates an aerobic environment and maintains the mixed liquor in suspension. The microorganisms interact with the wastewater to create a biomass that is more amenable to physical settling. After a specified reaction period, mixed liquor is sent to a settling tank to separate and remove the accumulated solids. A portion of the settled solids is treated further and the remaining portion is returned to the reactor to maintain a specified microbial concentration in the mixed liquor.
[0004] A desirable microbial culture will decompose organic pollutants quickly and will form a floc to separate biosolids. Mean cell residence time (MCRT) is the average time the microbes are present to metabolize their food. For typical domestic waste water, the mean cell residence time generally falls within the range of five to fifteen days. Within these limits the beneficial treatment qualities of the floc generally improve with increased residence time. There is a direct relationship between mean cell residence time and effluent waste concentration.
[0005] Effluent discharges from wastewater treatment works must meet certain water quality limitations for selected pollutant parameters which are specified in discharge permits issued in accordance with the National Pollution Discharge Elimination System (NPDES). In order to meet the permitted effluent limits, wastewater treatment facilities are designed for a specified peak hydraulic capacity and a peak volumetric pollutant loading. The specified peak capacity and loading fix the size of the treatment facility. Still, in areas of residential or industrial growth, increased water use leads to increased wastewater production that, in turn, leads to increased hydraulic loading. Industrial processes may also produce occasional “shock” loadings of pollutants that may overwhelm the pollutant removal capabilities of the existing biological treatment facilities.
[0006] With the conventional activated sludge process, the maximum recommended volumetric pollutant loading rate is 0.6 (kg BOD 5 applied/m 3 -day). Some enhancements to the conventional activated sludge process can increase volumetric pollutant loading without compromising the quality of the effluent. The known processes include enhanced aeration techniques, contact stabilization and Kraus process systems. However, even with known enhancements, there is an upper limit for volumetric loading. For enhancement by the Kraus process, the upper limit is 1.6 (kg BOD 5 applied/m 3 -day) 1 . Modified aeration may raise the limit to 2.4 (kg BOD 5 applied/m 3 -day). Pure oxygen aeration systems may attain a volumetric loading of up to 3.3 (kg BOD 5 applied/m 3 -day), but are rarely used due to high implementation and maintenance costs.
[0007] When pollutant loading or hydraulic capacity limits are reached, treatment facilities face the risk of permit limit violations, the possibility of Federal or State enforcement action, and restrictions or prohibitions on domestic and industrial growth within the service area of the treatment works. Typically, wastewater treatment facilities undergo physical expansion to meet the needs of increased hydraulic loading. But, physical expansion is expensive and often requires additional land that may not be available adjacent to existing facilities.
[0008] Therefore, it is desirable to find a way to increase volumetric pollutant loading and hydraulic capacity without the need for physical plant expansion. A significant advantage of the present invention over prior art methods of enhanced activated sludge processes is that volumetric pollutant loading can be substantially increased with only minor modifications to existing physical facilities. In addition, it is also a feature and advantage of the present invention that the enhanced activated sludge process produces a sludge with improved settling characteristics. Improved settling characteristics allow increases in hydraulic loading without requiring an increase in the size of the physical elements of the activated sludge system. By the same token, new activated sludge treatment works can be constructed in smaller sizes and at lower costs than known systems. With the enhanced activated sludge process of the present invention, design parameters that reflect the increased hydraulic capacity and pollutant loading capability can be incorporated into the sizing of the required structural elements to reduce the construction cost of new treatment works.
[0009] Most operators of wastewater treatment facilities have little or no control over the quality of the influent coming to the treatment plant they operate. Variations in domestic and industrial water use necessarily give rise to hourly, daily and seasonal fluctuations in influent wastewater quality. In particular, certain industrial events can result in the discharge of a “shock” pollutant load into the wastewater collection system and ultimately into the treatment plant. Such shock loading can upset the balance of the microbial culture present in the activated sludge reactor with a resulting loss of wastewater treatment effectiveness. Shock loading events also raise the risk of violating NPDES permit limitations on effluent quality with corresponding potential penalties and fines. It is another advantage of the present invention that the enhanced activated sludge process offers improved resistance to upsets of the microbial culture. It is also a feature and an advantage of the present invention that operating conditions of the activated sludge reactor are maintained in a more uniform condition, more resistant to undesirable variation in influent water quality changes.
[0010] For the activated sludge process to function properly, certain nutrients must be available in adequate amounts. The principal nutrients are nitrogen and phosphorus. While these nutrients are necessary for wastewater treatment, they may cause problems for aquatic life in the receiving waters where the treated effluent is discharged. Accordingly, the concentration of these nutrients in wastewater effluent is often limited by the NPDES discharge permit of the treatment facility. In these situations wastewater treatment facilities must include nutrient removal as part of the overall treatment process. In some cases the influent is nutrient deficient, requiring both the addition of nutrients and their subsequent removal. It is known in the art that nutrients may be added into the activated sludge process by chemical addition or, if digesters are present at the treatment works, by the recycling of digester supernatant.
[0011] Nutrient removal may be accomplished by any one of many suspended growth and attached growth processes that are known in the art. However, these systems often require the construction and operation of additional reactors and clarifiers, adding substantially to the cost of wastewater treatment. Therefore, it is a feature of the present invention that the enhanced activated sludge process can provide effective nutrient removal without the construction of separate nutrient removal reactors.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] [0012]FIG. 1 is a process diagram of a common configuration for a conventional activated sludge treatment facility.
[0013] [0013]FIG. 2 is a process diagram for a conventional activated sludge treatment facility with a Kraus process modification.
[0014] [0014]FIG. 3 is a process diagram for an enhanced activated sludge process according to a preferred embodiment of the present invention.
[0015] [0015]FIG. 4 is a chart illustrating the relationship between influent and return activated sludge (RAS) versus time according to a preferred embodiment of the present invention.
[0016] [0016]FIG. 5 is a chart illustrating the relationship between mixed liquor suspended solids (MLSS) in the reaeration and general aeration zones versus time according to a preferred embodiment of the present invention.
[0017] [0017]FIG. 6 is a chart illustrating the relationship between respiration rate in the reaeration and general aeration zones versus time according to a preferred embodiment of the present invention.
[0018] [0018]FIG. 7 is a chart illustrating the relationship between dissolved oxygen concentrations in the Kraus and reaeration zones versus time according to a preferred embodiment of the invention.
[0019] [0019]FIG. 8 is an exemplary comparative table of plant performance factors for volumetric loading, hydraulic loading and nutrient removal during periods before and after implementation of the present invention
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0020] Set forth below is a description of what is currently believed to be the preferred embodiments or best examples of the claimed inventions. Future and present alternatives and modifications to the preferred embodiments are contemplated. Any alternatives or modifications which make insubstantial changes in function, in purpose, in structure or in result are intended to be covered by the claims of this patent.
[0021] Physical Characteristics
[0022] While it is within the understanding of the invention that the claimed treatment processes can be incorporated into the design and construction of new treatment facilities, the best mode of practicing the invention involves the retrofitting of existing treatment works. FIG. 1 depicts a process diagram of a conventional activated sludge treatment system. Commonly, the activated sludge treatment step will be preceded by a physical settling process and may be followed by supplemental treatment prior to discharge at the treatment plant outfall. Therefore the influent 10 refers to the influent stream entering the aeration reactor 12 and the effluent 11 refers to the effluent stream leaving the settling tanks 13 . The aeration reactor 12 may be a single basin or may be partitioned into multiple zones to facilitate operation and maintenance. The settling basin 13 may also consist of one or more operating units. Process piping 14 , 15 , 16 conveys the solids collected from the settling basin to one or more locations. For example, a process line 14 may return activated sludge to the upstream side of the aeration basin 12 . Other process lines 15 , 16 may route activated sludge to digesters 17 or to a waste process for thickening or disposal. The process lines 14 , 15 , 16 may include a combination of valves, pumps and automated controls as are known in the art to provide the treatment plant operator with the ability to control the volume of sludge drawn from the settling basin 13 and the portion of the withdrawn sludge that is directed through each process line.
[0023] [0023]FIG. 2 is a schematic illustrating an activated sludge treatment system that has been modified according to the Kraus process. The Kraus process involves adding one or more process lines 18 to return digester supernatant and, optionally, digested sludge from the digester 17 to the aeration basin 12 . The return flow from the digester passes through a reaeration basin 19 prior to being reintroduced to the reactor 12 for the general aeration of the activated sludge.
[0024] In order to employ the enhanced activated sludge treatment process of the present invention in an existing conventional activated sludge system, the general aeration reactor 12 should preferably be partitioned into subsets of the total reactor volume. The size and number of partitioned subsets may be dictated by operational convenience or other factors as it is not significant to the result obtained by the present invention. Alternatively, additional basins may be constructed adjacent to the existing aeration basin and hydraulicly connected with associated piping and channels. In this alternative, the collection of separately constructed basins comprise the aeration reactor 12 that is to be partitioned.
[0025] [0025]FIG. 3 shows the general aeration basin 12 of a conventional activated sludge treatment process that has been partitioned into sixteen discreet aeration zones 20 a - 20 p of generally equal volume. Aeration equipment, as is known in the art, is present in the aeration zones 20 a - 20 p to transfer oxygen to the mixed liquor. In the preferred embodiment, six of the sixteen aeration zones (37.5% by volume) are removed from the initial general aeration process and reserved for the receipt of return activated sludge (RAS). These six zones are the reaeration zones 22 a - 22 f of the present invention. RAS enters the reaeration zones 22 a - 22 f at the upstream end and exits at the downstream end into the general aeration zones 24 . Of the six reaeration zones 22 a - 22 f two (33% by volume) are reserved as Kraus zones 26 for operation according to the Kraus process. In the Kraus zones 26 digester supernatant is combined with the return activated sludge. The contents are reaerated prior to being returned to the general aeration zones 24 .
[0026] The preferred embodiment also includes a biological selector 30 upstream of the general aeration zones 24 that is normally operated in an anoxic state. When operated in this manner, the dissolved oxygen concentration is typically between 0.0 mg/l and 0.2 mg/l. The biological selector 30 can be operated in oxic, anoxic and anaerobic conditions as desired to stress the biological culture in the selector and promote a desirable sludge type in the aeration phase.
[0027] The control of return activated sludge rates, waste activated sludge rates and supernatant addition is regulated in the preferred embodiment by process automation. Readings from respirometers 25 , solids meters 31 , and on-line RedOx monitors 32 are calibrated against laboratory analyses. Once calibrated, the readings are combined with the results of settleable solids testing to dictate process variable set points (such as flow rates and dissolved oxygen) to achieve overall process control.
[0028] Operating Conditions
[0029] The enhanced activated sludge treatment method of the preferred embodiment involves controlling selected conditions in the aeration phase of the treatment process. First, the return flow rate of activated sludge from the settling basin 13 to the upstream side of the aeration phase is preferably maintained at approximately 30% of the influent 10 to the aeration phase as illustrated in FIG. 4. While the preferred return rate is 30%, the process remains effective for return rates in the range of 25% to 60% of the influent flow rate. The return rate has an inverse correlation to the total suspended solids (TSS) concentration of the RAS. At low sludge return rates, as employed in the preferred embodiment, the solids concentration of the RAS may be as high as 20,000 ppm.
[0030] The sludge volume index (SVI) of the mixed liquor in the general aeration phase, as measured from a sample drawn preferably at a point between the aeration phase and the settling phase is an indication of the settling characteristics of the sludge. Generally, the SVI for the present invention can be expected to fall within the range of 40-80. For the preferred embodiment, the expected range is 40-60. Activated sludge return rates on the higher end of the beneficial range are appropriate where the SVI is similarly high.
[0031] Limiting the volume of the return activated sludge as described above results in a heavier solids concentration in the return line 14 than in the influent line 10 . The additional solids are then retained in the reaeration zones 22 a - 22 f of the aeration phase so that the concentration of mixed liquor suspended solids (MLSS) in the reaeration zones 22 a - 22 f is typically 8,000-12,000 ppm as compared to the concentration of MLSS in the general aeration zones 24 which is typically 3,000-5,000 ppm. In cold weather conditions, the MLSS in the general aeration zones 24 is slightly higher with typical concentrations of 5,000-6,000 ppm. The relationship of solids concentrations in the general aeration zones 24 , reaeration zones 22 a - 22 f and return sludge are illustrated in FIG. 5.
[0032] The respiration rate of the biological culture varies between the selector 30 , reaeration zones 22 a - 22 f and the general aeration zones 24 as illustrated in FIG. 6. When operating according to the preferred embodiment, the respiration rate in the reaeration zones 22 is consistently lower than the respiration rate of the general aeration zones 24 . The respiration rate, also known as the specific oxygen uptake rate (SOUR) is used an indicator of sludge age. A high SOUR measured in the selector 30 indicates that the sludge age is too low and sludge wasting should be reduced. A low SOUR measured in the general aeration zones 24 indicates that the sludge age is too high and sludge wasting should be increased.
[0033] Process controls on the means of aeration, as are known in the art, allow the operator to selectively adjust the concentration of dissolved oxygen (DO) in the reaeration zones 22 . In the preferred embodiment, the DO concentration in the mixed liquor at the downstream end of the Kraus zones 26 is typically 1.5 mg/l-3.0 mg/l. If ammonia nitrogen is present in the effluent 12 of the aeration phase, the DO concentration in the Kraus zones 26 is increased. The non-Kraus reaeration zones 22 c - 22 f are operated with the least amount of aeration that is necessary to maintain the solids of the mixed liquor in suspension. Typically, the DO concentration at the downstream end of the reaeration zones 22 c - 22 f is 0.1 mg/l-0.3 mg/l.
[0034] The differential aeration between the Kraus zones 26 and the other reaeration zones 22 c - 22 f has the effect of enhancing nitrogen removal. Where conventional, single stage nitrification has a 70% nitrogen removal efficiency, the differential aeration of the preferred embodiment increases the nitrogen removal efficiency to 95%. The desired differential aeration can be expressed as a ratio between the DO concentrations, the downstream ends of the Kraus zones 26 and the other reaeration zones 22 c - 22 f . In the preferred embodiment, that ratio is typically greater than 5:1. Ratios as low as 2:1 are also known to achieve improved nitrogen removal efficiency.
[0035] The combination of aeration partitioning, return activated sludge rate control, and differential MLSS concentrations described above create an improved solids type with low and stable SVI. The high MLSS in the reaeration zones 22 provides buffering capacity for shock pollutant loadings that resists typical process upsets and increases the volumetric loading capacity to values as much as six times the maximum loading capacity reported for conventional activated sludge systems with Kraus process modifications. The low and stable SVI produces gains in hydraulic capacity of 50% in the preferred embodiment. The further operation of differential DO concentrations in the reaeration zones 22 c - 22 f and the Kraus zones 26 enhances nutrient removal efficiency. Resulting nutrient removal rates achieved by the enhanced process of the preferred embodiment are typically 0.005 lbs. N/lb. VSS as an annual average and 0.010 lbs. N/lb. VSS during warm weather seasons. The performance factors expected for typical municipal wastewater treatment plants before and after practicing the described method are reported in FIG. 8.
[0036] The above description is not intended to limit the meaning of the words used in the following claims that define the invention. Rather, it is contemplated that future modifications in structure, function or result will exist that are not substantial changes and that all such unsubstantial changes in what is claimed are intended to be covered by the claims. | An enhanced activated sludge wastewater treatment method increases volumetric pollutant loading, hydraulic loading capacity and nutrient removal efficiency at a conventional activated sludge wastewater treatment plant. The method describes the control of return activated sludge rates, and the operation of partitioned aeration and reaeration zones according to measured properties of the mixed liquor to achieve the claimed benefits. Operating an existing treatment plant according to the enhanced treatment method provides a more consistent treatment process that is resistant to shock loading and increases plant capacity without the need for costly construction and operation of additional reactors and clarifiers. | 2 |
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates in general to an air bag device that is mounted in a motor vehicle and expands an air bag to protect a vehicle passenger upon a vehicle collision, and more particularly to a curtain air bag device that is mounted on an inside side wall part of a vehicle cabin (or passenger room) and expands a curtain-like air bag to protect both front and rear seat passengers upon a vehicle collision.
[0003] 2. Description of the Related Art
[0004] In order to clarify the present invention, the background of the curtain air bag device will be briefly described in the following with the aid of published documents.
[0005] One of the curtain air bag devices hitherto proposed is shown in Japanese Laid-open Patent Application (Tokkai) 2003-291771, which has an elongate or curtain-like air bag that, when not in use, is compactly wound up and neatly received in an elongate holding space that extends from a front pillar to a rear pillar of the vehicle body along a roof side rail. When the vehicle encounters a vehicle collision, such as side-on collision or the like, the curtain like air bag is ejected from the elongate holding space while quickly expanding toward the interior of the vehicle cabin having an outside surface thereof pressed against inside surfaces of side windows (when closed) of the vehicle. With such expansion of the air bag, front and rear seat passengers, namely, side portions of their heads are safely protected.
[0006] More specifically, the curtain air bag device of the Japanese Laid-open Application comprises an elongate or curtain-like air bag (viz., air bag proper) that is sized to protect both a front seat passenger and a rear seat passenger, an inflator that feeds the air bag with an inflating gas, and a tension strap that is fixed to a front end of the air bag. Upon expansion of the air bag, the tension strap become tightened to retain the expanded air bag at a given right position.
[0007] The curtain like air bag is made of two (viz., inner and outer) base fabrics stitched up together and comprises a front expandable portion that protects the front seat passenger, a rear expandable portion that protects the rear seat passenger, a conduit portion that extends between respective upper parts of the front and rear expandable portions to fluidly connect the two expandable portions, and a non-expandable fabric portion that is not fed with the inflating gas.
[0008] The front and rear expandable portions are generally the same in size and shape.
[0009] The non-expandable portion is provided below the conduit portion and extends between the front and rear expandable portions. That is, upon expansion of the air bag, the non-expandable fabric portion serves as a retainer for retaining or keeping a given distance between the front and rear expandable portions. With such non-expandable fabric portion and the above-mentioned tension strap, the passenger head protection effect of the two expandable portions is assuredly carried out upon a vehicle collision.
[0010] In the curtain air bag device as mentioned hereinabove, it is very important to compactly and correctly wind up the air bag in a flattened condition before being set in the elongate holding space. More specifically, if the flattened air bag is not properly wound up, it becomes very difficult to properly set the wound up air bag in the given holding space. If the setting of the wound up air bag in the holding space is not made properly, effective and reliable expansion of the air bag is not expected upon a vehicle collision.
[0011] One measure for eliminating the above-mentioned difficulty is described in Japanese Laid-open Patent Application (Tokkai) 2004-175304, which is an automatic air bag folding device by which the flattened air bag is compactly wound up. Thus, the air bag thus compactly wound up can be easily put into a right position of the holding space.
[0012] The automatic air bag folding device of the publication will be briefly described in the following with the aid of FIGS. 8 to 11 of the accompanying drawings.
[0013] As is seen from the drawings, the automatic air bag folding device 100 generally comprises a table 111 that has an upper surface 110 on which a flattened air bag 101 is to be flatly placed. The table 111 has a pocket “P” whose bottom is denoted by numeral 121 .
[0014] The automatic air bag folding device 100 further comprises an air nozzle (not shown) that feeds the flattened air bag 101 with a pressurized air to expand the air bag 101 thereby separating inner and outer base fabrics 101 a and 101 b of the air bag 101 from each other as shown in FIG. 8 , and first and second pressing blocks 151 and 153 that, as is seen from FIG. 9 , are moved leftward to compress the expanded portion of the air bag 101 to produce first and second flattened portions 102 a and 102 b that extend in opposite directions. As shown in FIG. 8 , the table pocket “P” is so sized as to receive the expanded part of the air bag 101 , and as shown in FIG. 9 , the first flattened portion 102 a is sandwiched between the first pressing block 151 and an after-mentioned third pressing block 140 , and the second flattened portion 102 b is sandwiched between the second pressing block 153 and a side wall of the table pocket “P”.
[0015] The automatic air bag folding device 100 further comprises a bobbin rod (or saber member) 158 that winds therearound a remained flattened portion 103 of the air bag 101 to produce a wound up mass 104 of the flattened air bag 101 as is seen from FIG. 10 , and a pushing plate 155 that functions to push and place the first flattened portion 102 a onto the wound up mass 104 as is seen from FIG. 11 .
[0016] The automatic air bag folding device 100 further comprises a locating pin 131 that is projectable from the table 111 and the third pressing block 140 that receives the projected locating pin 131 to tightly put therebetween a given part of the flattened air bag 101 for assuring positioning of the flattened air bag 101 on the table 111 . As shown, for assuring the positioning of the air bag 101 , the given part is formed with an opening (no numeral) into which the locating pin 131 projects.
[0017] In the following, the process of winding up the flattened air bag by using the automatic air bag folding device 100 will described with the aid of the drawings.
[0018] First, a flattened air bag 101 is flatly placed on the surface 110 of the table 111 , and then the given part of the air bag 101 is retained by the locating pin 131 and the third pressing block 140 , as will be understood from FIG. 8 .
[0019] Then, as is seen from FIG. 8 , the first and second pressing blocks 151 and 153 are moved to a position near the pocket “P” where a first part of the flattened air bag 101 is tightly put between these two pressing blocks 151 and 153 and a second part of the flattened air bag 101 is placed in the pocket “P” without restraint. Then, as is seen from the drawing, by feeding the flattened air bag 101 with a compressed air, the second part of the air bag 101 is expanded and thus the inner and outer base fabrics 101 a and 101 b there of are separated from each other, as shown.
[0020] Then, as is understood from FIGS. 8 and 9 , the first and second pressing blocks 151 and 153 are moved leftward in the drawing to compress the expanded portion of the air bag 101 . With this, first and second flattened portions 102 a and 102 b of the air bag 101 are produced as is seen from FIG. 9 .
[0021] Then, as is understood from FIGS. 9 and 10 , the first and second pressing blocks 151 and 153 are moved away from the third pressing block 140 leaving the first and second flattened portions 102 a and 102 b therebetween.
[0022] Then, as is seen from FIG. 10 , the remained flattened portion 103 of the air bag 101 is wound up by the bobbin rod 158 to form the wound up mass 104 of the air bag 101 . As is seen from this drawing, by turning the bobbin rod 158 in a counterclockwise direction, the wound up mass 104 moves leftward, that is, toward the third pressing block 140 while enlarging the size thereof.
[0023] As is seen from FIG. 11 , when coming leftward on the table 111 , the wound up mass 104 finally falls into the pocket “P”. Then, the pushing plate 155 is moved in a given way indicated by an arrow “X” for placing the first flattened portion 102 a onto the wound up mass 104 , as shown.
[0024] Then, the bobbin rod 158 is pulled out from the wound up mass 104 .
[0025] It is to be noted that the wound up mass 104 thus produced has a cylindrical, long and narrow shape whose axis extends in a direction perpendicular to the surface of the drawing of FIG. 11 . As has been mentioned hereinabove, the wound up mass 104 , which is the wound air bag 101 , is received in the elongate holding space that is provided by the side upper limited area, viz., the side roof rail 9 (see FIG. 1 ) of the vehicle cabin.
SUMMARY OF THE INVENTION
[0026] However, due to the inherent construction, the automatic air bag folding device of the above-mentioned Japanese Laid-open Patent Application (Tokkai) 2004-175304 is applicable only to air bags of a type that, in a flattened condition, has substantially same front and rear expandable portions. More specifically, the air bags should be of a type in which, when it is flattened, the height of the front expandable portion is substantially same as that of the rear expandable portion. If air bags that are to be wound up are of a type that does not satisfy the above-mentioned shape, that is, if, for example, the front and rear expandable portions have different sizes, the work of winding up the flattened air bag by the bobbin rod 158 is not properly and readily made. That is, in such case, due to the size difference between the front and rear expandable portions, the bobbin rod 158 can't hold respective lower ends of such two expandable portions at the same time, as will be understood when referring to FIG. 10 . That is, when the front expandable portion is larger than the rear expandable portion, the lower end of the front expandable portion is placed much below that of the rear expandable portion, and thus, the bobbin rod 158 has to hold only the lower end of the larger front expandable portion. In this case, the lower end of the smaller rear expandable portion is left loosed. Many tries have revealed that a satisfied wound up mass of the air bag is obtained only when the bobbin rod 158 extending in parallel with an upper edge of the air bag holds the respective lower ends of the front and rear expandable portions at the same time.
[0027] However, in these days, various types of motor vehicles have made their debut. As is easily known, respective spaces provided in the vehicle cabin for permitting a smoothed expansion of the front and rear expandable portions of the air bag beside the front and rear seats vary according to the types of the motor vehicle. That is, for example, when the motor vehicle is of a coupe type, a relatively larger space is provided beside the front seat and a relatively smaller space is provided beside the rear seat.
[0028] Thus, if the above-mentioned known curtain like air bag device is simply mounted in the vehicle without taking any device, it inevitably occurs, upon a vehicle collision, that the front and rear expandable portions, which have the same size, are ejected into the larger and smaller spaces while being expanded. Of course, this is not desirable because of occurrence of a time difference between the time when the front expandable portion shows its best protection performance and the time when the rear expandable portion shows its best protection performance. In other words, due to difficulty in advancing in the smaller space, the rear expandable portion takes a much time to reach the head of the rear seat passage as compared with the front expandable portion.
[0029] Furthermore, if sizes of the front and rear expandable portions of the air bag are determined in accordance with sizes of the spaces respectively provided beside the front and rear seats of the coupe type motor vehicle, that is, if the rear expandable portion is made smaller than the front expandable portion, compact and proper winding of the flattened air bag around the bobbin rod 158 is not achieved.
[0030] It is therefore an object of the present invention to provide a curtain air bag device which is free of the above-mentioned drawbacks.
[0031] That is, according to the present invention, there is provided a curtain air bag device in which a front expandable portion and a rear expandable portion of an air bag are different in size and can exhibit their passenger protection performance in substantially the same manner without producing a time difference therebetween.
[0032] Furthermore, according to the present invention, there is provided a curtain air bag device in which even when the front and rear expandable portion of an air bag are different in size, the air bag in a flattened condition can be properly and compactly wound up around a bobbin rod.
[0033] That is, according to the present invention, there is provided a curtain air bag device whose curtain like air bag comprises a front expandable portion and a rear expandable portion which are different in size, and a non-expandable fabric portion which serves to allow the entire construction of the air bag in an flattened condition to take a generally rectangular shape which is suited for compactly winding up the flattened air bag and neatly putting the wound up mass of the air bag into an air bag holding space defined in the vehicle cabin.
[0034] In accordance with a first aspect of the present invention, there is provided a curtain air bag device for use in a motor vehicle to protect vehicle passengers upon a vehicle collision, which comprises an air bag that, when not in use, is wound up and put in a holding space provided in a side wall part of a passenger room of the vehicle, the air bag having a longitudinally extending upper edge that is to be fixed to the inside side wall part and a longitudinally extending lower edge that is spaced from the longitudinally extending upper edge by a given distance, the longitudinally extending upper and lower edges extending on and along first and second imaginary lines respectively; and an inflator that is installed in the motor vehicle for feeding the air bag with an inflating gas to expand the same upon the vehicle collision, wherein the air bag comprises a plurality of expandable portions that include a larger expandable portion that has upper and lower edges respectively extending on and along the first and second imaginary lines and a smaller expandable portion that has an upper edge extending on and along the first imaginary line and a lower edge spaced from said second imaginary line by a given distance; and a non-expandable portion having a size-compensating part that extends from the lower edge of the smaller expandable portion to said second imaginary line.
[0035] In accordance with a second aspect of the present invention, there is provided a curtain air bag device for use in a motor vehicle to protect front and rear seat passengers upon a vehicle collision, which comprises an air bag that, when not in use, is wound up and put in an elongate holding space provided by a roof side rail of the vehicle, the air bag having a longitudinally extending upper edge that is to be fixed to the roof side rail and a longitudinally extending lower edge that is spaced from the longitudinally extending upper edge by a given distance, the longitudinally extending upper and lower edges respectively extending on and along first and second imaginary lines which are substantially in parallel with each other; and an inflator that is installed in the motor vehicle for feeding the air bag with an inflating gas to expand the same upon the vehicle collision, wherein the air bag comprises a plurality of expandable portions that include a larger expandable portion that has upper and lower edges respectively extending on and along the first and second imaginary lines and a smaller expandable portion that has an upper edge extending on and along the first imaginary line and a lower edge spaced from the second imaginary line by a given distance; and a non-expandable portion having a size-compensating part that extends from the lower edge of the smaller expandable portion to the second imaginary line.
[0036] In accordance with a third aspect of the present invention, there is provided an air bag for use in a curtain air bag device, which comprises mutually overlapped inner and outer base fabrics that are connected to each other to form a plurality of expandable portions that include a larger expandable portion that has upper and lower edges respectively extending on and along first and second imaginary lines and a smaller expandable portion that has an upper edge extending on and along the first imaginary line and a lower edge spaced from the second imaginary line by a given distance; and a non-expandable fabric portion that is connected to at least one of the inner and outer base fabrics, the non-expandable fabric portion having a size-compensating part that extends from the lower edge of the smaller expandable portion to the second imaginary line.
BRIEF DESCRIPTION OF THE DRAWINGS
[0037] Other objects and advantages of the present invention will become apparent from the following description when taken in conjunction with the accompanying drawings, in which:
[0038] FIG. 1 is a schematic view of a curtain air bag device of a first embodiment of the present invention, showing a condition wherein an air bag which is in a flattened condition is loosely exposed to a vehicle cabin;
[0039] FIG. 2 is a schematic view of the air bag in a flattened condition, which is not wound up yet;
[0040] FIG. 3 is a sectional view taken along the line “III-III” of FIG. 2 ;
[0041] FIG. 4 is a view similar to FIG. 2 , but showing an air bag that is used in a curtain air bag device of a second embodiment of the present invention;
[0042] FIG. 5 is a sectional view taken along the line “V-V” of FIG. 4 ;
[0043] FIG. 6 is a view similar to FIG. 2 , but showing an air bag that is used in a curtain air bag device of a third embodiment of the present invention;
[0044] FIG. 7 is a view similar to FIG. 2 , but showing an air bag that is used in a curtain air bag device of a fourth embodiment of the present invention; and
[0045] FIGS. 8 to 11 are schematic views depicting a process for winding up a flattened air bag, which is a known process.
DETAILED DESCRIPTION OF THE EMBODIMENTS
[0046] In the following, four embodiments E- 1 , E- 2 , E- 3 and E- 4 of the present invention will be described in detail with reference to the accompanying drawings.
[0047] For ease of understanding, various directional terms, such as, right, left, upper, lower, rightward and the like are used in the following description. However, these terms are to be understood with respect to only a drawing or drawings on which a corresponding element or portion is shown.
[0048] Referring to FIGS. 1 to 3 , particularly FIG. 1 , there is shown a curtain air bag device E- 1 of a first embodiment of the present invention. As will be described hereinafter, the curtain air bag device E- 1 is constructed to be used in a coupe type motor vehicle.
[0049] FIG. 1 shows a motor vehicle in which the curtain air bag device E- 1 is mounted on a curved roof side rail 9 of a motor vehicle 1 having a flattened air bag 11 A of the device E- 1 put out from a given elongate holding space of the air bag device E- 1 and thus loosely exposed to a vehicle cabin (or passenger room).
[0050] It is to be noted that the motor vehicle 1 shown in the drawing is of a coupe type whose swelled roof has the highest part at a front portion and gradually lowers as a portion nears the end of the vehicle 1 . Due to the inevitable shape of the coupe type, the vehicle 1 has a larger front side window 4 and a smaller rear side window 5 that are partitioned by a center pillar 7 of the vehicle 1 . The larger front side window 4 is defined when a side door “SD” takes a closed position in a door opening of the vehicle body. The smaller rear side window 5 is formed in a rear side panel of the vehicle body. As shown, the height of the larger front side window 4 is greater that that of the smaller rear side window 5 .
[0051] Designated by numeral 2 is a backrest of a front seat which is placed beside a rear area of the larger front side window 4 , and designated by numeral 3 is a backrest of a rear seat which is placed beside a rear area of the smaller rear side window 5 , as shown.
[0052] Designated by numerals 6 and 8 are front and rear pillars of the vehicle body that put therebetween the center pillar 7 . The curved roof side rail 9 extends from a top of the front pillar 6 to that of the rear pillar 8 . The center pillar 7 has a top connected to a rear half part of the curved roof side rail 9 , as shown.
[0053] The curtain air bag device E- 1 comprises a curtain like air bag (viz., air bag proper) 11 A, an inflator (not shown) that feeds the air bag 11 A with an inflating gas, a tension strap 12 that has a rear end fixed to a front lower portion of the air bag 11 A and extends forward, and a plurality of connecting pieces 13 that connect an upper edge of the air bag 11 A to the curved roof side rail 9 . The inflator is placed at a lower part of the rear pillar 8 .
[0054] When the curtain air bag device E- 1 is properly assembled and mounted to a proper position of the vehicle cabin, the air bag 11 A, which has been wound up, is neatly and compactly received in an elongate holding space that is provided by the curved roof side rail 9 .
[0055] As will be described in detail hereinafter, before being put into the elongate holding space, the wound up air bag 11 A is received in a cylindrical sleeve (not shown) that is formed with a plurality of slits. That is, upon operation of the curtain air bag device E- 1 , the slits are broken by the expanding air bag 11 A permitting a rapid ejection of the expanding air bag 11 A into the vehicle cabin from the elongate holding space.
[0056] As shown the flattened air bag 11 A comprises a front expandable portion 21 , a rear expandable portion 22 , a conduit portion 23 that extends between respective upper portions of the front and rear expandable portions 21 and 22 to fluidly connect the two expandable portions 21 and 22 , a gas inlet portion 24 that is provided at a rear upper part of the rear expandable portion 22 , and a non-expandable fabric portion 25 A that integrally extends downward from respective parts of the front and rear expandable portions 21 and 22 and the conduit portion 23 . If desired, the front and rear expandable portions 21 and 22 may be provided with respective gas inlet portions. Of course, in this case, the conduit portion 23 is not needed.
[0057] The front and rear expandable portions 21 and 22 are hollow and have respective upper parts connected to front and rear ends of the conduit portion 23 . Within the gas inlet portion 24 , there is installed a cylindrical protective fabric 26 for protecting the air bag 11 A from a highly heated inflating gas discharged from the inflator.
[0058] As is seen from FIGS. 2 and 3 , the air bag 11 A is made of two basic fabrics that are stitched up to each other. That is, the two basic fabrics are an inner base fabric 14 that faces the interior of the vehicle cabin and an outer base fabric 15 that faces outside of the vehicle. These two base fabrics 14 and 15 are overlaid and stitched along a given path indicated by a broken line 16 of FIG. 2 .
[0059] As will be understood from FIGS. 2 and 3 , the inner base fabric 14 is generally rectangular in shape and participates in forming respective parts of the front and rear expandable portions 21 and 22 , the conduit portion 23 and the gas inlet portion 24 and an entire part of the non-expandable fabric portion 25 A.
[0060] While, the outer base fabric 15 is shaped to have a larger front portion, a smaller rear portion and a narrow middle portion that extends between the larger front and smaller rear portions. In other words, the outer base fabric 15 has a shape corresponding to the shape defined by the given path denoted by the broken line 16 in FIG. 2 . Thus, the outer base fabric 15 participates in forming respective parts of the front and rear expandable portions 21 and 22 , the conduit portion 23 and the gas inlet portion 24 .
[0061] It is to be noted that the outer base fabric 15 does not participate in forming the non-expandable fabric portion 25 A.
[0062] For example, the inner and outer base fabrics 14 and 15 are each made of a fabric that is woven from 66 Nylon (trade name) of 315 denier and has a mass per unit area of 200 g/m 2 . The fabric is coated with a rubber or silicone resin. Of course, the material of the inner and outer base fabrics 14 and 15 is not limited to the above-mentioned one. That is, various types of material may be used for the fabrics 14 and 15 as long as they exhibit a satisfied performance as the material for the air bag 11 A.
[0063] Furthermore, as is seen from FIGS. 2 and 3 , particularly FIG. 2 , the inner and outer base fabrics 14 and 15 at portions that constitute the front expandable portion 21 are stitched by a given length to constitute a gas flow controlling part 17 . With this gas flow controlling part 17 , the inflating gas directed into the front expandable portion 21 is separated to upper and lower gas flows. For strengthening the gas flow controlling part 17 , each end of the part 17 is stitched circularly, which is indicated by numeral 18 . If desired, such gas flow controlling parts may be provided at other portions for obtaining a desirable gas flow in the expanded air bag 11 A.
[0064] Denoted by numerals 19 , 19 are portions where the inner and outer base fabrics 14 and 15 are stitched. With such stitched portions 19 , 19 , the gas flow in the expanded air bag 11 A is suitably controlled.
[0065] As is seen from FIG. 2 , when the air bag 11 A is in a flattened condition, an upper edge of the front expandable portion 21 and that of the rear expandable portion 22 are aligned to constitute a straight upper edge 27 or a first imaginary line.
[0066] In the illustrated example of the air bag 11 A, the height of the rear expandable portion 22 is about a half of that of the front expandable portion 21 .
[0067] As is mentioned hereinabove, the non-expandable fabric portion 25 A has a front curved edge integral with a rear edge of the front expandable portion 21 , a highly raised upper edge integral with a lower edge of the conduit portion 23 , a curved middle edge integral with a front edge of the rear expandable portion 22 and a rear upper edge integral with a lower edge of the rear expandable portion 22 .
[0068] The non-expandable fabric portion 25 A has a straight lower edge that is aligned with a straight lower edge of the front expandable portion 21 to constitute a straight lower edge 28 or second imaginary line. As shown, the straight lower edge 28 and the above-mentioned straight upper edge 27 are in parallel with each other.
[0069] The straight lower edge 28 is formed with two cuts 28 a and 28 a. With such cuts 28 a and 28 a, projection of the wound up air bag 11 A from the elongate holding space is rapidly carried out upon operation of the curtain air bag device E- 1 .
[0070] As shown, a rear edge of the non-expandable fabric portion 25 A is aligned with a rear edge of the rear expandable portion 22 to constitute a rear edge 29 of the air bag 11 A.
[0071] A front edge 30 of the air bag 11 A is constituted by a front edge of the front expandable portion 21 . As shown, the front edge 30 and the above-mentioned rear edge 29 are substantially parallel to each other. Accordingly, when the air bag 11 A is not expanded and thus it is flattened and flatly placed on a table, the air bag 11 A is entirely rectangular in shape as is seen from FIG. 2 .
[0072] As will be understood from FIG. 1 , the tension strap 12 has a front end fixed to a lower portion of the front pillar 6 . Usually, the tension strap 12 is compactly received in the front pillar 6 . However, upon a vehicle collision, the tension strap 12 is pulled out from the front pillar 6 by the air bag 11 A under expanding and finally holds the front lower part of the expanded air bag 11 A, as is seen from FIG. 1 . Due to the holding work of the tension strap 12 , the expanded air bag 11 A can be held in a stable position.
[0073] As is seen from FIGS. 1 and 2 , the connecting pieces 13 are provided to spaced portions of the upper edge 27 of the air bag 11 A and fixed to the roof side rail 9 by means of connecting bolts or the like.
[0074] In the following, the process of compactly winding up the flattened air bag 11 A and neatly putting the compactly wound up air bag 11 A into the elongate holding space defined by the roof side rail 9 will be described in detail with reference to FIGS. 1 and 2 and FIGS. 8 to 11 .
[0075] First, as has been mentioned hereinabove with the aid of the drawings of FIGS. 8 to 11 , the flattened air bag 11 A (see FIG. 2 ) is wound up. It is now to be noted that due to the generally rectangular shape of the air bag 11 A in a flattened condition, winding of the flattened air bag 11 A around the bobbin rod 158 (see FIG. 10 ) is compactly and properly achieved. That is, when finally wound up, the straight lower edge 28 of the flattened air bag 11 A is placed at a center of the wound up mass of the air bag, like the leading end (see FIG. 10 ) of the remained flattened portion 103 that is pinched by the bobbin rod 158 . Furthermore, upper portions of the inner and outer base fabrics 14 and 15 , that extend along the straight upper edge 27 and are separated from each other, constitute two flattened portions that correspond to the first and second flattened portions 102 a and 102 b (see FIG. 11 ).
[0076] Then, the wound up air bag 11 A is received in a cylindrical sleeve (not shown) that has a plurality of slits. As has been mentioned hereinabove, such slits are provided for permitting a rapid ejection of the expanding air bag 11 A into the vehicle cabin. The cylindrical sleeve has a plurality of aligned openings for putting therethrough the connecting pieces 13 of the air bag 11 A.
[0077] Then, the cylindrical sleeve having therein the wound up air bag 11 A is put into the elongate holding space and the connecting pieces 13 are fixed to the roof side rail 9 . Then, the tension strap 12 is set in the right position of the front pillar 6 .
[0078] Although not shown in the drawings, a suitable decorative member is installed along the roof side rail 9 to conceal both the cylindrical sleeve and tension strap 12 from view.
[0079] In the following, operation of the curtain air bag device E- 1 will be described with reference to FIG. 1 .
[0080] For ease of understanding, the following description is directed to a case wherein front and rear seats ( 2 and 3 ) carry thereon respective passengers.
[0081] As is described hereinabove, in a normal condition, the wound up air bag 11 A is neatly received in the elongate holding space of the roof side rail 9 together with the cylindrical sleeve.
[0082] When the vehicle encounters a vehicle collision, such as side-on collision or the like, a collision sensor (not shown) operates the inflator, so that the inflator feeds the wound up air bag 11 A with an inflating gas through the gas inlet portion 24 . With this, the front and rear expandable portions 21 and 22 of the air bag 11 A are rapidly expanded while breaking the cylindrical sleeve and rushing out into the vehicle cabin. During this, the tension strap 12 is pulled out from the front pillar 6 and finally holds the front lower part of the expanding air bag 11 A.
[0083] Thus, the expanded front and rear expandable portions 21 and 22 protect heads of the front and sear seat passengers, more specifically, side portions of their heads respectively. As is seen from FIG. 1 , upon expansion of the air bag 11 A, the non-expandable fabric portion 25 A provided between the expanded front and rear expandable portions 21 and 22 functions to safely hold a right shoulder of the rear seat passenger.
[0084] In the following, advantages expected from the curtain air bag device “E- 1 ” of the first embodiment of the present invention will be described.
[0085] First, as is mentioned hereinabove, upon a vehicle collision, the front and rear expandable portions 21 and 22 of the air bag 21 assuredly protect the heads of the front and rear seat passengers. Furthermore, the non-expandable fabric portion 25 A can safely protect the right shoulder of the rear seat passenger.
[0086] Second, even when the front and rear expandable portions 21 and 22 have different sizes due to the inevitable style (viz., coupe style) of the motor vehicle, provision of the non-expandable fabric portion 25 A provides the flattened air bag 11 A with an entirely rectangular shape. This rectangular shape is quite advantageous when the flattened air bag 11 A is needed to be wound up for producing the wound up mass of the air bag 11 A that is to be neatly put in the elongate holding space of the roof side rail 9 . Actually, the lower edge of the flattened air bag 11 A that extends along the second imaginary line 28 (see FIG. 2 ) can be entirely pinched or held by the bobbin rod 158 (see FIG. 10 ), which assures production of the compactly wound up mass of the flattened air bag 11 A. That is, if such non-expandable fabric portion 25 A is not provided, the winding up action of the flattened air bag 11 A by the bobbin rod 158 is not properly carried out because the bobbin rod 158 can not hold the respective lower edges of the front and rear expandable portions 21 and 22 at the same time.
[0087] Third, because the front and rear expandable portions 21 and 22 of the air bag 21 are so sized as to suit to front and rear spaces that are respectively provided beside the front and rear seats ( 2 and 3 ) under the curved roof of the coupe style motor vehicle, expansion of such front and rear expandable portions 21 and 22 is smoothly and reliably made.
[0088] Fourth, even when a vehicle collision brings about breakage of the side window glasses, the expanded air bag 11 A that is rectangular in shape due to provision of the non-expandable fabric portion 25 A blocks bursting of the broken glass pieces into the vehicle cabin, which protects the vehicle passengers from the glass pieces.
[0089] Referring to FIGS. 4 and 5 , there is shown a flattened air bag 11 B that is used in a curtain air bag device “E- 2 ” of a second embodiment of the present invention.
[0090] As is seen from these drawings, in this embodiment “E- 2 ”, a non-expandable fabric portion 25 B has an extra part 15 ′ of the outer base fabric 15 , that extends downward from a lower edge of the rear expandable portion 22 to the lower edge of the inner base fabric 14 . Due to provision of such extra part 15 ′, the advantageous function of the non-expandable fabric portion 25 B is much assured.
[0091] Referring to FIG. 6 , there is shown a flattened air bag 11 C that is used in a curtain air bag device “E- 3 ” of a third embodiment of the present invention. This curtain air bag device “E- 3 ” is suitable for the motor vehicles of a type that has a smaller space beside the front seat and a larger space beside the rear seat.
[0092] As is seen from the drawing, the flattened air bag 11 C comprises front and rear expandable portions 41 and 42 which are fluidly connected by a shorter conduit portion 43 , and a non-expandable fabric portion 25 C. As shown, in this air bag 11 C, the height of the front expandable portion 41 is smaller than that of the rear expandable portion 42 , and the non-expandable fabric portion 25 C is constructed of only an extra part of the inner base fabric 14 . The non-expandable fabric portion 25 C has a straight upper edge integral with a lower edge of the front expandable portion 41 , a rear rounded upper edge integral with a lower edge of the shorter conduit portion 43 and a rear slanted edge integral with a front slanted edge of the rear expandable portion 42 .
[0093] Referring to FIG. 7 , there is shown a flattened air bag 11 D that is used in a curtain air bag device “E- 4 ” of a fourth embodiment of the present invention. This curtain air bag deice “E- 4 ” is suitable for the motor vehicles of a type that has a larger space beside the front seat, a smaller space beside a middle seat and another smaller space beside the rear seat.
[0094] As is seen from the drawing, the flattened air bag 11 D comprises a larger front expandable portion 51 , a smaller middle expandable portion 52 and a smaller rear expandable portion 53 which are fluidly connected by front and rear conduit portions 54 and 55 , and a non-expandable fabric portion 25 D. As shown, also in this air bag 11 D, the non-expandable fabric portion 25 D is constructed of only an extra part of the inner base fabric 14 . The non-expandable fabric portion 25 D has a front edge integral with a rear edge of the front expandable portion 51 , a front raised edge integral with a lower edge of the front conduit portion 54 , a front lowered edge integral with a lower edge of the middle expandable portion 52 , a rear raised edge integral with a lower edge of the rear conduit portion 55 and a rear lowered edge integral with a lower edge of the rear expandable portion 53 .
[0095] In the foregoing description, it is explained that stitching is used for constituting the air bag from two base fabrics 14 and 15 . Of course, besides the stitching, other known methods may be used for providing the air bag. One is a method of employing “Jacquard weaving” that automatically provides woven fabrics with bag portions during weaving.
[0096] The entire contents of Japanese Patent Application 2007-091886 filed Mar. 30, 2007 are incorporated herein by reference.
[0097] Although the invention has been described above with reference to the embodiments of the invention, the invention is not limited to such embodiments as described above. Various modifications and variations of such embodiments may be carried out by those skilled in the art, in light of the above description. | An air bag, when in a flattened condition, has a longitudinally extending upper edge and a longitudinally extending lower edge. The longitudinally extending upper and lower edges extend on and along first and second imaginary lines respectively. The air bag comprises a plurality of expandable portions that include a larger expandable portion that has upper and lower edges respectively extending on and along the first and second imaginary lines and a smaller expandable portion that has an upper edge extending on and along the first imaginary line and a lower edge spaced from the second imaginary line by a given distance; and a non-expandable portion having a size-compensating part that extends from the lower edge of the smaller expandable portion to the second imaginary line. | 1 |
PRIORITY CLAIM
[0001] This patent application is a U.S. National Phase of International Patent Application No. PCT/NL2008/050628, filed Oct. 2, 2008, which claims priority to co-pending European Patent Application No. 07118512.8, filed Oct. 15, 2007, and co-pending European Patent Application No. 07121454.8, filed Nov. 23, 2007, the disclosures of which are incorporated herein by reference in their entirety.
FIELD
[0002] The present disclosure relates to positioning in the eye and adjustment of an accommodating intraocular artificial lens, a lens with variable optical power, comprising two optical elements which are adapted to mutually move (by shift, rotation or combination thereof) in a direction perpendicular to the optical axis wherein the optical elements have such a shape that the optical elements exhibit, in combination, different optical powers at different relative positions.
BACKGROUND
[0003] For purposes of the present disclosure, the following abbreviations and definitions will be used.
[0004] “IOL” for intraocular lens, which is an artificial lens for the eye implanted by an eye surgeon, including, but not limited to, monofocal lenses, multifocal lenses, phakic and a-phakic lenses and accommodating intraocular lenses.
[0005] “MIOL” for monofocal intraocular lens, which is a traditional intraocular lens with one focus.
[0006] “AIOL” for accommodating intraocular lens, which is an artificial lens which changes diopter power to focus the eye, driven by the natural mechanism for focusing by the ciliary muscle.
[0007] “AAIOL” for adjustable accommodating intraocular lens, of which the basic power can be adjusted, generally to improve emmetropia of the eye during surgery or post-surgery.
[0008] “Ciliary body” refers to numerous muscle filaments interspersed in a tissue structure, alternatively referred to as “ciliary body” or “ciliary mass” or “ciliary process”. The term “ciliary body” is used throughout the present disclosure to refer to the combination of tissues in which the muscle filaments are interspersed.
[0009] The basic principles of an AIOL applied in the present disclosure with moving optical elements are disclosed in European Patent No. 1720489, International Patent Publication No. 2007/015640, International Patent Publication No. 2006/118452 and International Patent Publication No. 2007/027091. These prior art AIOLs comprise the two optical elements and driving means driving at least one of the optical elements to execute a movement relative to the other optical element. These driving means are adapted to be coupled with the ciliary body to restore accommodation. Note that the ciliary body can drive a lens in the eye via two mechanisms. Firstly, the ciliary body can drive a lens in the eye indirectly by changing the shape of the capsular bag, which bag subsequently changes the shape of the lens, similar to functioning of the natural human lens. Secondly, the ciliary body can drive a lens in the eye directly by changing the shape of a lens via changes in inter-ciliary body distance (and, to a lesser degree, inter-sulcus distance). The present disclosure concerns such AIOLs with haptics positioned in the sulcus of the eye and constructions to use ciliary body and sulcus movements to drive the AIOL. Note that the embodiments disclosed herein apply not only to AIOLs with optics moving perpendicular to the optical axis but also to other IOLs and AIOLs and, therefore, apply to various types of AIOLs.
[0010] An AIOL must adhere to a number of strict approval and surgical requirements: for example, have sufficient accommodating power to allow full accommodation in the majority of eyes, be safe, for example, be manufactured from biocompatible materials, be preferably foldable for proper implantation, implantation preferably by injection, and the like. In addition, such lens must also be adapted to be (a) positioned in a proper, firm, and predictable position in the eye and should (b) preferably have means to adapt the basic focal power of the AIOL, for example, prior to surgery, at the end of surgery or post-surgery (after some time of wearing the lens).
[0011] Note that especially AIOLs, will provide the patient with a spectacle-free life, and that correction of, for example, far-vision post-surgery, by, for example, spectacles, is limited. Other fixed corrections of basic optical power of the eye, for example, laser treatment of the cornea, are options, but this requires additional surgery and risk. Adjustability of the IOL or AIOL itself is highly preferable. Adaptations for (a) positioning of an AIOL and (b) post-implant adjustability of optical power of an IOL, including an AIOL resulting in an AAIOL, are the subjects of the present disclosure.
SUMMARY
[0012] The present disclosure describes several exemplary embodiments of the present invention.
[0013] One aspect of the present disclosure provides an accommodating intraocular artificial lens with variable optical power, comprising: two optical elements which are adapted to mutually move in a direction perpendicular to the optical axis wherein the optical elements are shaped such that the optical elements exhibit, in combination, different optical powers at different relative positions and haptics for positioning the optical elements, wherein at least one element of the lens is adapted to be positioned in the eye in a position anterior of the capsular bag and that the haptics are adapted to extend in the sulcus of the eye.
[0014] Another aspect of the present disclosure provides an accommodating intraocular lens system, comprising: two optical elements which are adapted to mutually move in a direction perpendicular to the optical axis, and an additional optical element wherein the optical elements are shaped such that the optical elements exhibit, in combination, different optical powers at different relative positions and haptics for positioning the optical elements, wherein at least one element of the lens is adapted to be positioned in the eye in a position anterior of the capsular bag and that the haptics are adapted to extend in the sulcus of the eye.
[0015] A further aspect of the present disclosure provides a method for inserting an adjustable accommodating intraocular lens system into an eye, the adjustable accommodating intraocular lens system comprising two optical elements which are adapted to mutually move in a direction perpendicular to the optical axis, and an additional optical element wherein the optical elements are shaped such that the optical elements exhibit, in combination, different optical powers at different relative positions and haptics for positioning the optical elements, wherein at least one element of the lens is adapted to be positioned in the eye in a position anterior of the capsular bag and that the haptics are adapted to extend in the sulcus of the eye, the method comprising (a) inserting two optical elements which are adapted to mutually move in a direction perpendicular to the optical axis, the optical elements have such a shape that the optical elements exhibit, in combination, different optical powers at different relative positions into the eye; and (b) inserting an additional optical element having a constant optical power into the eye, wherein the optical power of the adjustable accommodating intraocular lens system is adjusted by adjustment of at least one of the optical elements.
Positioning of AIOL Lens in the Sulcus
[0016] IOLs are nowadays generally implanted in the capsular bag after removal of the natural lens. However, AIOL function can be severely hampered by the natural shrinkage and hardening of the capsular bag, which hardly affects a monofocal, static IOL. It is an option to position an IOL or AIOL in the sulcus of the eye, a position outside of, preferably in front of, the capsular bag. Sulcus implant was common in the past for MIOLs for which it is now occasionally used, for example, when the capsular bag has been severely damaged and can not carry an IOL.
[0017] An AIOL in the sulcus is driven mainly by the ciliary body and, to a lesser degree, the sulcus itself. Preferably, the ciliary body has to connect to or contact the posterior part of the haptics, or a second flange on the posterior optical element.
[0018] Such accommodating intraocular artificial lens with variable optical power, comprising two optical elements which are adapted to mutually move in a direction perpendicular to the optical axis wherein the optical elements have such a shape that the optical elements exhibit, in combination, different optical powers at different relative positions and haptics for positioning the optical elements can be adapted to be positioned in the eye in a position anterior, in front of, the capsular bag by adapting at least one of the elements and its haptic for such a position. In particular, the haptics, which are directly connected to the optical elements, can be adapted to extend in the sulcus of the eye. Implants of intraocular lenses with haptics positioned in the sulcus were common in the past. These were all monofocal intraocular lenses which provided only one focal spot to the eye.
[0019] Accommodating intraocular lenses implanted in the sulcus have been described in U.S. Patent Publication No. 2007/0129799, which discloses a lens with (1) optical elements which move along the optical axis, which optical elements are separate from, not connected to, (2) a circular container, which is separate from, not connected to, (3) a circular haptics ring encompassing the ciliary body. International Patent Publication No. 2005/065600 and European Patent No. 1890650 describe an AIOL which provides accommodation due to ocular pressure and lens deformation along the optical axis rather than direct driving of the construction by the ciliary muscle. The haptics of this design are implanted separately from the rest of the construction and the haptics are designed for firm positioning of the construction in the sulcus and not for movement for driving optical mechanisms. The haptics of the AIOL described in the present disclosure are arranged to extend over only at least two sections of the circumference of the optical elements and do not circumferentially enclose the complete rim of the optical elements.
[0020] The haptics may comprise positioning means (for example, flanges, extending over, at least part, of the circumference of the haptics rim) which are adapted to be at least partially enclosed by the sulcus. It should be noted that the dimensions of the flanges should be chosen such that: (a) the flanges have a width such that the flanges fit into the sulcus and that (b) the flanges have a length such that the remaining rim of the accommodating lens construction touches against the ciliary body such that the compression force and compression distance of the ciliary muscle will translate through the remaining ciliary body in a shift of the optical elements and so provide accommodation to the eye. Consequently, this provides a kind of form locking between the sulcus as a whole and those parts of the lens functioning as haptics as a whole. Alternatively, at least one the flanges can be of such shape, or an additional flange can be added to the posterior optical element, so that the ciliary body directly engages, in combination, with the fit in the sulcus for positioning. This can be accomplished with, for example, haptics which comprise annular grooves, each enclosed by two protrusions adapted to enclose at least a section of the ciliary body thus located in the groove. Also, in this particular AIOL design, the base plate of the anterior optical element can be extended to form a flange for sulcus positioning and enclosure of the ciliary body anteriorly, and the base plate of the posterior element can be extended to enclose the ciliary body posteriorly (see also FIG. 4 ). For all above examples, shrinkage of the bag might even be beneficial because the shrunken capsular bag will support the lens construction at the posterior part.
[0021] The haptics need to fulfil two functions, i.e., the positioning of the lens and the haptics in the sulcus and the driving of the haptics by the ciliary body in the direction perpendicular to the optical axis. In a first exemplary embodiment, the haptics extend into the sulcus and are enclosed in the sulcus between the ciliary body and the iris, wherein the driving of the haptics takes place through a rim of the haptics located at the inner side of the sulcus. In a second exemplary embodiment, the haptics extend at both sides of the ciliary body, that is, one part of the haptics extend in the sulcus and the other side in the posterior side of the ciliary body. Also in this exemplary embodiment, the driving of the haptics takes place through a face of the haptics extending at the inner side of the ciliary body. It will be clear that the positioning of the lens requires that the haptics extend over such sections of lens that a proper positioning is obtained, whereas the driving of the haptics to drive the optical elements requires at least one, but preferably at least two, opposite sections.
[0022] Also, in case the drive of the optical elements is to be provided for by the sulcus as well, it is desirable when the haptics comprise positioning hooks or claws, providing a more permanent and sturdy positioning. This leads to a kind of form locking structure, however, not between the haptics and sulcus as a whole, but between the local parts thereof. The same counts when the haptic comprises pins, an even more permanent positioning or even fixation is achieved, as the form locking comprises a kind of form locking by enclosing. Yet another exemplary embodiment resides in the application of glue, possibly in combination with other positioning means, if only for initial positioning. As an alternative, yet another exemplary embodiment provides the feature that the flanges comprise a staggered part adapted to be partially enclosed by a part of the sulcus.
[0023] It should be noted that the dimensions of the flanges should be properly chosen such that: (a) the flanges have a thickness such that the flanges fit into the sulcus and that (b) the flanges protrude equally from two sides of the rim which, in turn, compresses the zonulae and touches against the ciliary body such that the compression force and compression distance of the ciliary muscle will translate through the remaining ciliary body in a shift of the optical elements. However, other means of positioning or ‘suturing’ are not excluded. Clearly, flange diameters should be chosen carefully to maximize ciliary body function on the AIOL in case additional flanges are added to enclose the ciliary body in a posterior and anterior plane.
Adjustability of Accommodating Intraocular Lens
[0024] All intraocular lenses, or lens systems, must have a basic optical power to correct the total refraction of the eye, resulting in an emmetropic eye, i.e., an eye which provides a sharp image at a distance. Standard fixed optical power intraocular lenses provide only this optical power, accommodating intraocular lenses can add variable power on top of this base power. However, in practice, emmetropia of eye is hardly ever reached despite modern refraction measuring equipment. The achieved refraction generally deviates by 0.5 to 1D from the desired refraction. Means to adjust any intraocular lens, including AIOLs, after implant are desirable. Note that for standard monofocal intraocular lenses the patient will have to wear spectacles anyway (generally, progressive spectacles) to which a minor correction for emmetropia can be easily added by the optician. However, true AIOLs promise a spectacle-free life, and such correction on spectacles is an option not preferred. In any case, pre-implant (prior to surgery), post-implant (at the end of surgery) or post-surgery (at any time after surgery) adjustability can benefit any IOL, including standard monofocal MIOLs.
[0025] In the AIOL design as disclosed, adjustability can be achieved by, for example, changing the size (shortening or lengthening) of at least one haptic which will shift the optical elements to a new resting position, as described in Dutch Patent Application No. 1028496 (FIG. 6) by application of a notches and grooves mechanical calibration system.
[0026] The optical power of an IOL or AIOL can be adapted or adjusted by, for example, the addition of at least one additional optical element, being a second optical element (in the case of, for example, monofocal, MIOL, or multifocal IOL) or being a third optical element (in the case of the AIOL designs as disclosed in this document which consist of two optical elements), which additional optical element can be integrated with the IOL or MIOL or AIOL, or the additional optical element can be separate from the IOL or MIOL or AIOL. The additional optical element has constant optical power, can be non-adjustable or adjustable (which is, when adjustable, only occasionally changed), can be added during surgery or added to the system after implantation (or, alternatively, adjustability by removal of an additional optical element). Addition of an additional optical element results in an adjustable AIOL system (“AAIOL system”), which additional optical element can be adapted to be positioned in the anterior or, alternatively, in the posterior chamber of the eye, in contact with or separate from the IOL or MIOL or AIOL.
[0027] With regard to the AIOL of the present disclosure, an additional optical element (in this case, a third optical element) can be an integral component of the adjustable AIOL system, i.e., physically connected to any component of the AIOL, for example, by a mechanical or chemical connection, which connection can be a rigid connection or an elastic connection. However, the third optical element can also be separate from the AIOL, for example, the third optical element be positioned in a different part of the eye. For example, an AAIOL system with the AIOL positioned in the sulcus and the additional third element positioned in the capsular bag. Firstly, the third element can be a lens fitted into an enclosure of the AIOL specifically adapted to enclose or be attached to the third optical element. Secondly, such lens can be positioned in the eye completely separate from the accommodating intraocular lens. For example, an AIOL positioned in the sulcus, as described hereinabove in combination with a lens in the capsular bag. Other combinations and positions are possible. Such lens can be a simple spherical lens of low optical value, for example, 0.5D, and additionally contain surfaces to correct for other aberrations of the eye, for example, astigmatism. Also, such third element lens can be of fixed optical power or of an adjustable optical power. Intraocular lenses adjustable for optical power have recently become available, such as those disclosed in International Patent Publication No. 03/058287.
[0028] Also, the third optical element can have at least one optical surface which forms a lens of variable optical power in combination with at least one additional optical surface on at least one of the optical elements of the AIOL of which the optical power varies with different positions of the additional surfaces relatively to each other. The power of the lens varies with lateral shift of the additional elements or, alternatively, a rotation of the additional element.
[0029] Various exemplary embodiments can be designed with a fixed-dioptric power lens (or, alternatively, a fixed-diopter adjustable power lens; the power is fixed in normal life, but only occasionally adjusted by an eye surgeon to ensure emmetropia of the un-accommodated eye) implanted in the capsular bag and a spatially separated accommodating optical element with flanges positioned in the sulcus of the eye. For example, in such a configuration the fixed-power lens, i.e., a standard monofocal IOL which replaces the natural lens, corrects for emmetropia, whereas the accommodative element, having a zero base refraction, delivers only the variable focusing power by the mutually shift in a direction perpendicular to the optical axis of the optical elements. Note that in all examples in the present disclosure, the surfaces of the optical elements which mutually shift in a direction perpendicular to the optical axis can be designed to either add or subtract optical power when moved in a certain direction. For the eye, however, an increase in diameter of the sulcus and ciliary body means a reduction in optical power of the natural lens. It is logical that an accommodating IOL adheres to those same principles. Also, note that for all examples in the present disclosure, the fixed optical power can be distributed over a fixed lens and the accommodative element. For example, the fixed element can have 20D to which 0-5D is added by the accommodative element or, for example, the fixed element can have 18D to which 2-7D is added by the accommodative element.
[0030] Several important advantages of uncoupled optics for refractive power and accommodation can be outlined: (i) the implantation of each optic can be accomplished by a standard IOL injector through a small incision reducing trauma to the patient eye; (ii) the constant power lens in the capsular bag limits shrinkage of the capsular bag and closes access to the anterior part of the posterior section of the capsular bag for floating cells which may cause PCO (posterior capsular opacification); and, (iii) the accommodative element positioned in the sulcus of the eye is not affected by the capsular bag shrinkage.
[0031] Accommodating IOL systems, with a component of shifting optical elements, can be comprised of a fixed lens, for example, a standard plate haptic or C-loop IOL, implanted in the capsular bag in its standard position in combination with a separate accommodating optical element with flanges positioned in the sulcus of the eye.
[0032] Other exemplary embodiments have an accommodative element for a presbyopic/phakic eye, i.e., an eye which still contains a transparent, non-cataracterous, but inelastic, non-accommodating, natural lens. Such separate accommodative element can restore accommodation and must be implanted outside the capsular bag in which the natural lens remains. Such implant can be positioned, for example, in the sulcus or in any other position in the eye where accommodative movement can be obtained to shift at least one optical element.
[0033] It is also possible to adapt the AAIOL with such a construction so that a shift can be provided of at least one optical element able to shift the basic refractive element along the optical axis. Such shift will also result in adjustment of the power of the AAIOL within the context of the optical system of the eye.
[0034] The adjustable accommodating optical lens system can be a complete unit inserted in one exemplary procedure by, for example, injection. However, a method for inserting an AAIOL system into an eye comprises the following steps: (a) inserting two optical elements which are adapted to mutually move in a direction perpendicular to the optical axis, the optical elements have such a shape that the optical elements exhibit, in combination, different optical powers at different relative positions into the eye and, (2) inserting a third, adjustable, optical element having a constant optical power into the eye. Adjustment can take place prior to surgery, during surgery (for example, just before the end of surgery, after the AAIOL is implanted in the eye) or after surgery (for example, several month after surgery when the eye is supposed to have healed and be stabilized, or, alternatively, years after surgery when the optical requirements of the eye can have changed due to aging). The optical power of the adjustable accommodating intraocular lens system is adjusted after implantation in the eye. The adjustment of the optical power can take place by amendment of the relative position of the optical element to the accommodating intraocular lens or the adjustment of the optical power takes can take place by insertion of the additional optical element to the accommodating intraocular lens.
BRIEF DESCRIPTION OF THE DRAWINGS
[0035] Various aspects of the present disclosure are described hereinbelow with reference to the accompanying figures.
[0036] FIG. 1 a is a schematic view of the natural eye;
[0037] FIG. 2 is a schematic view of the eye with an AIOL with flanges in the un-accommodated state according to one exemplary embodiment of the present invention;
[0038] FIG. 3 is a schematic view of the eye with an AIOL with flanges in the accommodated state according to one exemplary embodiment of the present invention;
[0039] FIG. 4 is a schematic view of the embodiment of FIG. 2 with an additional posterior flange forming a groove in combination with the anterior flange;
[0040] FIG. 5 is a schematic view of one exemplary embodiment of the eye with an AIOL (without basic refractive optics, only with accommodating optics) in combination with a separate fixed optical power or, alternatively, a fixed adjustable optical power lens, in this example, in the capsular bag;
[0041] FIG. 6 is a schematic view of a second exemplary embodiment of the eye with an AIOL with flanges and a posterior basic refractive optics in combination with a third optical element, in this example, an element with such a shape that movement of this element optical results in a variable lens in combination with an optical surface on any of the optical elements of the accommodative lens;
[0042] FIG. 7 is a schematic view of a third exemplary embodiment of the eye with an AIOL with flanges and a posterior basic refractive optics in combination with a third optical element, in this example, a fixed optical power or, alternatively, a fixed adjustable optical power lens, wherein this third optical element is a plano-convex lens fitted into an enclosure; and
[0043] FIG. 8 is a schematic view of the AIOL with flanges for positioning in the sulcus, seen from above, according to one exemplary embodiment.
DETAILED DESCRIPTION
[0044] FIG. 1 shows the basic schematics of the anterior part of the human eye. Note that in this particular example the eye is likely un-accommodated because the zonules are tense and the lens slightly flattened. Behind the cornea of the eye 1 is the anterior chamber 2 the iris 3 and the sclera 4 . The posterior chamber 5 is the space between the iris and the capsular bag 6 which contains the natural lens 7 . The sulcus 8 is positioned between the iris and the ciliary body 9 , wherein its width is indicated by the arrow 10 and is connected to several groups of zonules 11 and also includes the ciliary muscle. The arrow 12 indicates the distance over which the zonules can be collapsed.
[0045] FIGS. 2 and 3 show schematic views of the anterior part of the eye with an AIOL with flanges 13 positioned in the sulcus. The rim of the haptic of the accommodating intraocular lens 14 is in contact with the ciliary body. The haptic is connected via a connector 15 to either the posterior element 16 or the anterior optical element 17 . Note that complex surfaces which form a lens of variable optical power are schematically represented by two slanting surfaces on the inner side of each optical element. The capsular-rhexis 18 is the opening through which the natural lens is removed. The elastic connection spring which allows the optical element to shift has an opening 19 which is open when the lens is in an un-accommodated state of low dioptric power as shown in FIG. 2 and closed when the lens is in an accommodated state of high dioptric power as shown in FIG. 3 . In both figures, the rim of the haptics implanted anterior of the capsular bag has flanges 13 supporting the lens construction positioned in the sulcus. The length of the flanges is designed to position the rim of the optical elements of the AIOL construction at the ciliary body to allow the ciliary muscle to shift the optical elements.
[0046] FIG. 4 shows a schematic of the anterior part of the eye with an AIOL with additional posterior flanges 20 , additional to the anterior flanges illustrate in FIGS. 2 and 3 to support positioning and embracing the ciliary body.
[0047] FIG. 5 shows a schematic view of the anterior part of the eye with an AIOL as in earlier figures but without a basic refractive optics in combination with a basic refractive lens 21 implanted separately in the capsular bag. This lens can be either of fixed optical power or, alternatively, an adjustable lens. The relaxed state, or the un-accommodated, is shown; the accommodated state follows FIG. 3 .
[0048] FIG. 6 shows a schematic view of the eye with an AIOL with flanges and a posterior optical element which also carries basic refractive optics in combination with a third optical element 22 , in this exemplary embodiment, an element with such a shape that movement of this element (for example, shift or rotation) results in a variable lens, in combination with an optical surface on any of the other optical elements of the accommodative lens.
[0049] FIG. 7 shows a schematic view of the eye with an AIOL with flanges and a posterior basic refractive optics in combination with a third optical element 23 , in this exemplary embodiment, a lens of fixed optical power which can be adjustable. In this exemplary embodiment, a plano-convex lens is fitted into an enclosure with holding means 24 .
[0050] FIG. 8 shows a schematic outline of the AIOL with flanges for positioning in the sulcus, seen from above. Note that all accommodating lenses described hereinabove can also have the option to correct for aberrations of the overall optics of the eye, for example, astigmatism.
[0051] A number of exemplary embodiments for positioning as well as adjustability will be outlined hereinbelow. However, it will be clear to one of ordinary skill in the art that other embodiments for positioning in the sulcus of the eye of an AIOL as well as adjustability post-implant of any IOL, including any AIOL, within the scope of the appended claims may be devised.
Sulcus Positioning
[0052] One exemplary embodiment (shown in FIGS. 2 and 3 ) for positioning of the AIOL described in the sulcus has flanges 13 which extend from the base plate of the anterior element of the AIOL. The flanges have the appropriate width to ensure proper fit in the sulcus and have the appropriate length to ensure that the ciliary body is in contact with the rim 14 of the main body of the AIOL. At accommodation ( FIG. 3 ), the ciliary body and, to a degree, the sulcus, will move the optical elements of the AIOL to a position of higher optical diopter power compared to the relaxed state ( FIG. 2 ).
[0053] In a second exemplary embodiment ( FIG. 4 ), similar flanges extend from both the anterior element as well as the posterior element, with flanges 20 . In this exemplary embodiment, the ciliary body is enclosed by the four flanges and a transfer of force and movement of both ciliary body and the sulcus is ensured.
[0054] Both exemplary embodiments have already shown to be simply manufactured by a straightforward addition to the milling program to extend the base plate to form the flanges. Clearly, such lenses can comprise other constructions to extend the flanges, for example, extension of base plates by metal inserts, additional components, and so forth, but such additional components appear to be complex solutions to the same effect.
Adjustability
[0055] Firstly, one exemplary embodiment comprises the addition of an adjustable (for example, a light adjustable MIOL lens to the accommodative lens, resulting in an AAIOL system (see, for example, International Patent Publication No. WO 03/058287). FIG. 5 shows the addition of such an adjustable MIOL in the capsular bag. Clearly, the refractive power of the AIOL must be reduced in case of such addition and the power of the refractive unit.
[0056] Secondly, not illustrated, such an adjustable lens can be directly attached to the posterior or anterior element of the AIOL by gluing or by a number of mechanical means. Post-surgery adjustment of the adjustable lens provides an AAIOL which ensures emmetropia of the eye. Note that such adjustments are reversible and that such adjustments can be repeated several times.
[0057] The AIOL of the present disclosure changes the optical power of a lens formed by two optical elements which move perpendicular to the optical axis. Such a concept can be applied to add adjustability to the AIOL as well. A third optical element 22 ( FIG. 6 ) is added to the AIOL, of which at least one surface forms a variable lens in combination with an additional surface on any of the surfaces of the AIOL. The lens varies in optical power by either shift of the third element or, alternatively, by rotation over an axis, with the third element preferably connected to the AIOL by an elastic connection. Alternatively, such third element 23 can be added to the AIOL by holding means (in an enclosure) 24 . Such (occasional, adjusting) shift or rotation of the third element is most likely achieved by interference by an eye surgeon by moving the element in the eye by, for example, a surgical needle or forceps, through a small incision. However, electro-mechanical or magnetic or optical (by, for example, a surgical laser) options for such movement are possible with adaptations to the AIOL system.
[0058] Most simply, at least one holding means (in this example, partial enclosure) 24 ( FIG. 7 ) formed, in this example, by a rim or, alternatively, by at least two clamps can be designed to either partially enclose a low power MIOL or partially enclose an adjustable low power MIOL (or a third element with a complex optical surface which works in combination with an additional surface on the AIOL, as set forth hereinabove). Such MIOL or third element can be added before surgery (at the manufacturing stage), during surgery, or post-surgery (at any time). Such MIOL can be of a low positive or low negative power (for example, in the range of −2D to +2D), depending on requirements. Such MIOL can be thin (˜100-200 um thick) ensuring simple surgery through a small incision and hardly add to the thickness of the anterior optical element of the AAIOL (as shown in FIG. 7 ).
[0059] All patents, patent applications, publications and other documents referred to herein are incorporated by reference in their entirety. | An accommodating intraocular artificial lens with variable optical power, comprising two optical elements which are adapted to mutually shift in a direction perpendicular to the optical axis wherein the optical elements have such a shape that the optical elements exhibit, in combination, different optical powers at different relative positions. Flanges are adapted to position the anterior section of the haptics in the sulcus of the eye or, alternatively, the ciliary body is enclosed by a combination of anterior and posterior flanges. Also disclosed are methods to provide for an accommodating intraocular lens which is adjustable post-implant to ensure emmetropia of the eye. | 0 |
RELATED APPLICATIONS
[0001] This application is a continuation of U.S. application Ser. No. 11/047,920, filed Feb. 1, 2005, which is hereby incorporated by reference, and further claims priority to European Application No. EP 04 004 054.5, filed Feb. 23, 2004, which is hereby incorporated by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Technical Field
[0003] The invention relates to the use of meloxicam or a pharmaceutically acceptable salt thereof for preparing a pharmaceutical composition for the treatment or prevention of respiratory diseases in pigs.
[0004] 2. Background Information
[0005] Respiratory disease in pigs belongs to the most important health problems in swine production. Porcine respiratory disease is primarily caused by infectious agents, but environmental factors have a strong influence. The relevant pathogens include mycoplasmas, bacteria, and viruses (e.g., G. Christensen, V. Sorensen, and J. Mousing, Diseases of the Respiratory System, In: Diseases of Swine , B. E. Straw, S. D'Allaire, W. L. Mengeling, & D. J. Taylor (eds), Iowa State University Press, Ames, Iowa (1999) pp. 913-940).
[0006] The most important measures for the control of porcine respiratory disease are to improve herd management and housing conditions and introduce a vaccination program. However, if pigs have developed respiratory disease, they have to be treated.
[0007] Current therapy of porcine respiratory disease includes treatment with antibiotics. The successful use of various types of antibiotics is described, including β-lactams, quinolones, and tetracyclines (e.g., 1. Lang, M. Rose, E. Thomas, & E. Zschiesche, A Field Study of Cefquinome for the Treatment of Pigs with Respiratory Disease, Revue Med Vet 8-9, (2002) pp. 575-580).
[0008] It is known that cyclooxygenase-2 (COX-2) plays a relevant role in the pathophysiology of porcine pleuropneumonia caused by Actinobacillus pleuropneumoniae . Isolated porcine alveolar macrophages increase their COX-2 activity after exposure to Actinobacillus pleuropneumoniae (W. S. Cho & C. Chae, In vitro Effects of Actinobacillus pleuropneumoniae on Inducible Nitric Oxide Synthase and Cyclooxygenase-2 in Porcine Alveolar Macrophages, Am J Vet Res 64, (2003) pp. 1514-1518). Moreover, in situ hybridization (W. S. Cho & C. Chae, Expression of Cyclooxygenase-2 in Swine Naturally Infected with Actinobacillus pleuropneumoniae . Vet Pathol 40, (2003) pp. 25-31) and immunohistochemistry (W. S. Cho & C. Chae, Immunohistochemical Detection of Cyclooxygenase-2 in Lungs of Pigs Naturally Infected with Actinobacillus pleuropneumoniae , J Comp Pathol 127, (2002) pp. 274-279) showed increased COX-2 expression in lungs of pigs naturally infected with Actinobacillus pleuropneumoniae.
[0009] Moreover, it is well-known that acetylsalicylic acid (aspirin) can be used for the treatment of pigs with respiratory disease. However, little information on controlled clinical studies is available: for a review, see A. Laval, Utilisation des Anti-inflammatoires chez le Porc, Rec Méd Vét 168 (8/9) (1992) pp. 733-744. Ketoprofen, and, to a lesser extent, flunixin decrease fever induced by experimental infection with Actinobacillus pleuropneumoniae (J. M. Swinkels, A. Pijpers, J. C. Vernooy, A. Van Nes, & J. H. Verheijden, Effects of Ketoprofen and Flunixin in Pigs Experimentally Infected with Actinobacillus pleuropneumoniae , J Vet Pharmacol Ther 17, (1994) pp. 299-303). However, no effects on lung lesions were observed. Ketoprofen was further tested in a controlled, blinded clinical field study (M. F. De Jong, O, Sampimon, J. P. Arnaud, G. Theunissen, G. Groenland, & P. J. Werf, A Clinical Study with a Non Steroid Antiinflammatory Drug, 14, (1996) 659 IPVS). In this study, ketoprofen had no effect on clinical score, relapse, or cure rate.
[0010] Indomethacin alleviated experimental endotoxin-induced respiratory failure in pigs (N. C. Olson, T. T. Brown, J. R. Anderson, & D. L. Anderson, Dexamethasone and Indomethacin Modify Endotoxin-Induced Respiratory Failure in Pigs, J Appl Physiol 58, (1985) pp. 274-284).
[0011] Meloxicam is a non-steroidal anti-inflammatory compound that belongs to the oxicam class and exerts potent anti-inflammatory, anti-exudative, and anti-pyretic activity. The efficacy of meloxicam as an adjunctive therapy in the treatment of respiratory infections in cattle has been widely proven. Recently meloxicam was approved for the treatment of MMA (A. Hirsch et al., J Vet Pharmacol Therap 26 (2003) pp. 355-360) and locomotor disorders in pigs (G. Friton et al., Berl Münch Tierärztl Wschr 116 (2003) pp. 421-426).
[0012] A review article (P. Lees, The Pharmacokinetics of Drugs Used in the Treatment of Respiratory Diseases in Cattle and Pigs, (1991) pp. 67-74, Hatfield, U.K. Proc. Royal Vet. Coll.) focuses on pharmacokinetics used in the treatment of respiratory disease in cattle and pigs; however, non-steroidal anti-inflammatory drugs data for pigs was almost entirely lacking and only lists data for cattle including meloxicam.
[0013] The use of meloxicam in conjunction with antibiotics in bovine respiratory disease is well-established (H. Schmidt, H. Philipp, E. Salomon, & K. Okkinga, Effekte der zusätzlichen Gabe von Metacam (Meloxicam) auf den Krankheitsverlauf bei Rindern mit Atemwegserkrankungen, Der praktische Tierarzt 81 (2000) pp. 240-244) and registered in the EU. However, to date no information on the use of meloxicam in pigs with respiratory disease is publicly available.
[0014] Since the pharmacokinetics in pigs and cattle differ substantially for meloxicam (plasma half-time in cattle is 26 hours whereas it is 2.5 hours in pigs), there is no expectation that the successful use of meloxicam in cattle should also be beneficial for pigs. Moreover, the causative agents for bovine and porcine respiratory disease differ substantially.
[0015] The problem underlying the present invention was to provide a medication for the prevention or treatment of respiratory diseases in pigs, one of the most important health problems in swine production.
BRIEF DESCRIPTION OF THE INVENTION
[0016] It has been found surprisingly that meloxicam can be used for the treatment or prevention of respiratory diseases in pigs.
[0017] Accordingly, the invention relates to the use of meloxicam or a pharmaceutically acceptable salt thereof for preparing a pharmaceutical composition for the treatment or prevention of respiratory diseases in pigs.
[0018] Moreover, the invention relates to a method of treating or preventing respiratory diseases in pigs, which method comprises administering an effective amount of meloxicam to the pigs in need thereof.
[0019] Furthermore, the invention relates to veterinary preparation containing meloxicam as well as at least one antibiotic selected from the group consisting of β-lactams, quinolones, tetracyclines, sulfonamides, fenicoles, and macrolides.
[0020] Another aspect of the invention is a ready-to-use two-component system for the treatment of respiratory diseases in pigs, wherein:
(a) one component contains meloxicam and a pharmaceutically acceptable carrier; and (b) the other component contains at least one antibiotic selected from the group consisting of β-lactams, quinolones, tetracyclines, sulfonamides, fenicoles, and macrolides and a pharmaceutically acceptable carrier.
[0023] Still another aspect of the invention is an article of manufacture comprising packaging material contained within which is a composition consisting of meloxicam and a pharmaceutically acceptable carrier, and a label which indicates that the composition can be used to treat or prevent respiratory diseases in pigs.
BRIEF DESCRIPTION OF THE DRAWINGS
[0024] FIG. 1 shows the incidence of fever (rectal temperature≧40.56° C.) in percent following the first treatment in a group of pigs treated with oxytetracycline and meloxicam (♦), in a group of pigs treated with oxytetracycline alone (◯), and in the untreated control (Δ).
[0025] FIG. 2 shows the efficacy of meloxicam in drinking water in reducing lung lesions caused by experimental Swine Influenza Virus (SIV) infection on study days 7 and 14.
DETAILED DESCRIPTION OF THE INVENTION
[0026] Preferably the invention relates to the use of meloxicam or a pharmaceutically acceptable salt thereof for preparing a pharmaceutical composition in a form suitable for systemic or oral administration for the treatment or prevention of respiratory diseases in pigs. Meloxicam (4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide) of formula
[0000]
[0000] is an active substance which belongs to the group of NSAIDs (non-steroidal-anti-inflammatory drugs). Meloxicam and the sodium and meglumine salt thereof (N-methyl-D-glucamine salt) are described in EP-A-0 002 482 (corresponding to U.S. Pat. No. 4,233,299), each of which is hereby incorporated by reference.
[0027] Meloxicam may be used according to the invention in the form of a physiologically acceptable acid addition salt. By physiologically acceptable acid addition salts are meant, according to the invention, the meglumine, sodium, potassium, or ammonium salt, preferably the meloxicam meglumine salt.
[0028] In a further preferred embodiment, the pharmaceutical composition is administered corresponding to a daily dose of meloxicam ranging from 0.01 mg/kg to 5.0 mg/kg, preferably from 0.1 mg/kg to 3.5 mg/kg, in particular from 0.2 mg/kg to 2.0 mg/kg.
[0029] The pharmaceutical composition is preferably administered in a form suitable for injection, in particular for intramuscular injection, or in form of water soluble granules for administration via drinking water or as top dressing on feed.
[0030] A suitable injection formulation is disclosed, for example, in Example 25 of EP-A-0 002 482. Furthermore, such injection solutions may additionally contain excipients selected from among citric acid, lecithin, gluconic acid, tartaric acid, phosphoric acid and EDTA or the salts thereof as disclosed in the Examples 1 to 5 of the International Patent Application WO 01/97813 (corresponding to U.S. Patent App. Pub No. 2002/0035107), each of which is hereby incorporated by reference. Moreover, an injection solution of meloxicam for needleless injections is disclosed in the International Patent Application WO 03/049733 (corresponding to U.S. Patent App. Pub No. 2003/0119825), each of which is hereby incorporated by reference.
[0031] Suitable water soluble granules for administration via drinking water or as top dressing on feed are, for example, disclosed in the International Patent Application PCT/EP03/11802 (corresponding to U.S. Patent App. Pub No. 2004/0234596), each of which is hereby incorporated by reference.
[0032] In a preferred embodiment of the invention, the meloxicam granules contain a binder which may be selected from among hydroxypropylmethylcellulose, polyvinylpyrrolidone, gelatine, starch, and polyethylene glycol ether, preferably hydroxypropylmethylcellulose, polyvinylpyrrolidone, and polyethylene glycol ether, and most preferably hydroxypropylmethylcellulose and polyvinylpyrrolidone.
[0033] In another preferred embodiment of the invention, meloxicam granules contain a sweetener, which may be selected from among sodium saccharine, aspartame, and SUNETT® (acesulfame K), preferably sodium saccharine or aspartame.
[0034] Particularly preferred according to the invention are meloxicam granules containing a flavoring agent which may be selected from among vanilla, honey flavoring, apple flavoring, and contramarum, preferably honey flavoring and apple flavoring.
[0035] Also particularly preferred are meloxicam granules in which the carrier is selected from among lactose, glucose, mannitol, xylitol, sucrose, and sorbitol, preferably glucose, lactose, or sorbitol, more preferably glucose or lactose, and most preferably glucose.
[0036] Most preferred are the following granules of meloxicam recipes:
EXAMPLE A
0.6% Meloxicam Granules
[0037]
[0000]
g/100 g
Meloxicam
0.6
Meglumine
0.42
Hydroxypropylmethylcellulose
3.00
Povidone
2.00
Glucose monohydrate
93.98
EXAMPLE B
1.2% Meloxicam Granules
[0038]
[0000]
g/100 g
Meloxicam
1.2
Meglumine
0.84
Hydroxypropylmethylcellulose
3.00
Collidone 25
2.0
Glucose Monohydrate
92.96
EXAMPLE C
0.6% Meloxicam Granules
[0039]
[0000]
g/100 g
Meloxicam
0.6
Meglumine
0.42
Pharmacoat 606
4.0
Macrogol 6000
1.0
Acesulfame K
0.3
Lactose
93.68
EXAMPLE D
0.6% Meloxicam Granules
[0040]
[0000]
g/100 g
Meloxicam
0.6
Meglumine
0.42
Pharmacoat 606
4.75
Macrogol 6000
0.25
Acesulfame K
0.3
Liquid vanilla flavoring
0.05
Lactose
93.63
[0041] Particularly preferred are meloxicam granules in which the content of meloxicam is between 0.05% and 4%, preferably between 0.1% and 2%, preferably between 0.3% and 1.8%, more preferably between 0.4% and 1.5%, and most preferably 1.2%. Also particularly preferred are meloxicam granules which contain meglumine and meloxicam in a molar ratio of about 9:8 to 12:8, preferably 10:8.
[0042] Meloxicam can be used according to the invention to treat or prevent respiratory diseases in any breed of swines. Preferably pigs selected from the swine breeds American Landrace, American Yorkshire, Angeln Saddleback, Arapawa Island, Ba Xuyen, Bantu, Bazna, Beijing Black, Belarus Black Pied, Belgian Landrace, Bentheim Black Pied, Berkshire, Black Slavonian, British Landrace, British Lop, Bulgarian White, Cantonese, Chester White, Czech Improved White, Danish Landrace, Dermantsi Pied, Duroc, Dutch Landrace, Fengjing, Finnish Landrace, French Landrace, German Landrace, Gloucestershire Old Spots, Guinea Hog, Hampshire, Hereford, Hezuo, Iberian, Italian Landrace, Jinhua, Kele, Krskopolje, Kunekune, Lacombe, Large Black, Large Black-white, Large White, Lithuanian Native, Mangalitsa, Meishan, Middle White, Minzhu, Mong Cai, Mukota, Mora Romagnola, Moura, Mulefoot, Neijiang, Ningxiang, Norwegian Landrace, Ossabaw Island, Oxford Sandy and Black, Philippine Native, Pietrain, Poland China, Red Wattle, Saddleback, Spots, Swabian-Hall, Swedish Landrace, Tamworth, Thuoc Nhieu, Tibetan, Turopolje, Vietnamese Potbelly, Welsh, and Wuzhishan, in particular American Landrace, Belgian Landrace, British Landrace, Danish Landrace, Dutch Landrace Finnish Landrace, French Landrace, German Landrace, Italian Landrace, and Pietrain can be treated with meloxicam according to the present invention.
[0043] Furthermore preferred is the administration of meloxicam is in conjunction with an antibiotic, preferably selected from the group consisting of β-lactams, quinolones, tetracyclines, sulfonamides, fenicoles, and macrolides. Most preferred are amoxicillin, oxytetracycline, florfenicol, tylosin, tilmicosin, and sulfamethazine.
[0044] The dose of antibiotic is not critical per se and depends strongly on the different efficacies of the antibiotics used. As a rule up to 150.0 mg/kg, preferably from 0.1 mg/kg to 120 mg/kg, in particular from 10 mg/kg to 110 mg/kg of an antibiotic are co-administered together with meloxicam.
[0045] The following dose ranges are most preferred:
[0000]
Amoxicillin:
5 mg/kg to 30 mg/kg, in particular about 10 mg/kg;
Oxytetracycline:
20 mg/kg to 70 mg/kg, in particular about 30 mg/kg;
Florfenicol:
10 mg/kg to 20 mg/kg, in particular about 15 mg/kg;
Tylosin:
10 mg/kg to 25 mg/kg, in particular about 16 mg/kg;
Tilmicosin:
5 mg/kg to 30 mg/kg, in particular 10 mg/kg to
20 mg/kg; and
Sulfamethazine:
80 mg/kg to 150 mg/kg, in particular about 100 mg/kg.
[0046] The phrase “co-administration” (or “administration in conjunction with”), in defining use of meloxicam and an antibiotic, is intended to embrace administration of each agent in a sequential manner in a regimen that will provide beneficial effects, in particular, reduction of the symptoms of the respiratory disease in the affected pig of the drug combination. The phrase also is intended to embrace co-administration of these agents in a substantially simultaneous manner, such as in a single capsule or injection solution having a fixed ratio of these active agents or in multiple, separate capsules for each agent.
[0047] Accordingly, meloxicam and the antibiotic may be co-administered in a combined form, or separately or separately and sequentially wherein the sequential administration is preferably close in time.
[0048] Preferably the medicament according to this invention is used for the prevention or treatment of Porcine Respiratory Disease Complex in growing or fattening pigs; or for the prevention or treatment of respiratory diseases in pigs caused by mycoplasmas, in particular Mycoplasma hyopneumoniae, Mycoplasma hyorhinis , for the prevention or treatment of respiratory diseases in pigs caused by bacteria in particular Actinobacillus spp., in particular Actinobacillus pleuropneumoniae, Bordetella bronchiseptica, Pasteurella multocida, Arcanobacterium pyogenes, Streptococcus spp., and Staphylococcus spp., or for the prevention or treatment of respiratory diseases in pigs caused by viruses, in particular Swine Influenza Virus, Aujetzky's Virus, Porcine Reproductive and Respiratory Syndrome Virus, Porcine Circovirus, and Transmissible Gastroenteritis and Porcine Respiratory Coronavirus.
[0049] Most preferably the medicament according to this invention is used for the prevention or treatment of respiratory diseases in pigs caused by Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Bordetella bronchiseptica, Pasteurella multocida, Streptococcus suis , Swine Influenza Virus, and Porcine Reproductive and Respiratory Syndrome Virus.
[0050] The Examples that follow serve to illustrate the use of meloxicam according to the invention. They are intended solely as possible procedures described by way of example, without restricting the invention to their content.
EXAMPLE 1
Efficacy of Meloxicam in Pigs with Experimental Actinobacillus Pleuropneumoniae Infection
[0051] The study was a controlled, randomized, and blinded exploratory study under experimental conditions with a parallel group design.
[0052] Crossbred pigs of about 10 weeks of age were challenged with a single intranasal inoculation of Actinobacillus pleuropneumoniae . The next day, pigs were included in the study and treated if they fulfilled the following inclusion criteria: rectal temperature≧40° C. and clinical symptoms of acute or subacute infectious respiratory disease.
[0053] Twenty-four (12 castrated male and 12 female) pigs were included and randomly allocated to three treatment groups with 8 pigs per group. The treatment groups were:
[0000]
Group
Treatment
1
untreated
2
oxytetracycline
3
oxytetracycline and meloxicam
[0054] Meloxicam was administered as 0.5% solution, at 0.5 mg/kg daily on three consecutive days, oxytetracycline as 20% long-acting solution (OXYTET® 200) at 20 mg/kg as single injection.
[0055] Relevant criteria for the evaluation of efficacy were incidence of fever, clinical parameters of respiratory disease, deaths, and lung lesions at necropsy 10 days after first treatment or after spontaneous death. The percentage of affected lung tissue was calculated by lobe and averaged for the total lung.
[0056] Challenge with Actinobacillus pleuropneumoniae lead to severe pleuropneumonia within 12 hours.
[0057] The incidence of fever (rectal temperature≧40.56° C.) following the first treatment was lower in group 3 (♦) than in groups 1 (Δ), and 2 (◯) (cp. FIG. 1 ).
[0058] The best treatment response in clinical parameters was observed in group 3.
[0059] The number of pigs which died during the three days following first treatment is displayed below.
[0000]
Group (n = 8 per group)
Deaths
1
7
2
1
3
0
[0060] The mean extent of lung lesions was less severe in group 3 than in the other groups (see below).
[0000]
Group
Lung lesions (%)
1
60
2
35
3
14
[0061] Meloxicam in addition to antibiotic treatment effectively reduced fever, clinical symptoms of respiratory disease, deaths, and the extent of lung lesions in pigs with experimental Actinobacillus pleuropneumoniae -infection.
EXAMPLE 2
Efficacy of Meloxicam in Drinking Water in Experimental Swine Influenza Virus Infection
[0062] The aim of this study was to test the efficacy of meloxicam granules dissolved in drinking water in pigs experimentally infected with Swine Influenza Virus (SIV).
[0063] The study was an open, negative controlled randomized laboratory study carried out according to GCP at one site.
[0064] Meloxicam granules containing 6 mg meloxicam per gram were offered to the pigs in the treatment groups (A+B) via drinking water in a concentration of 1 g granules per liter drinking water ad libitum for 7 consecutive days. This resulted in an actual meloxicam uptake of 0.8 mg per kg body weight per day. The pigs in the control group (C) received municipal drinking water ad libitum.
[0065] 30 pigs were infected with SIV on study day 0.10 pigs were allocated to each of the three groups A, B, and C. Treatment (groups A and B) started after SIV challenge on the same day.
[0066] The study animals were clinically examined daily on study days 0 to 7 and 14. They were weighed on study days 7 and 14. All animals of group A and 5 animals of group C were euthanized and necropsied on study day 7; the remaining study animals, group B and 5 study animals of group C, on study day 14.
[0067] It is the major finding of this study that meloxicam granules administered continuously in the drinking water at an approximate daily dose of 0.8 mg/kg body weight significantly alleviated the development of lung lesions caused by experimental infection with SIV during the first week after challenge. FIG. 2 shows the quantity of lung lesions by lung lobe on study days 7 and 14.
[0068] On study day 7 the percentage of lung tissue affected with SIV-related lesions (median value) was 8.9% in meloxicam group A and 23.8% in the control group (5 study animals of group C).
[0069] Moreover, meloxicam-treated pigs reached significantly higher weight gains during the two weeks following infection than untreated controls. Mean daily weight gain in the interval study day 0 to 7 was 557 g in meloxicam group A and 257 g in the control (5 study animals of group C). In the interval study day 0 to 14, mean daily weight gain was 629 g in meloxicam group B and 486 g in the control (5 study animals of group C).
[0070] The area under the curve of the clinical index score (CIS), a sum of the relevant clinical parameters, over study days 0 to 7 was significantly smaller in groups A and B than in group C.
[0071] Thus oral treatment with meloxicam granules at a dose of 0.8 mg meloxicam per kg body weight per day for 7 consecutive was an efficacious treatment for SIV infection.
EXAMPLE 3
Field Trial Regarding the Effect of Meloxicam in the Porcine Respiratory Disease Complex (PRDC) in Growing/Fattening Pigs
Materials and Methods
[0072] A medium scale farm (560 sows) with a previous history of recurring PRDC episodes was selected. A double-blinded randomized study was carried out with the selection of 162 growing animals with a mean age of 90 days at the onset of PRDC clinical signs. Animals were randomly allocated to 8 pens and divided into two treatment groups, with respect to equal sex ratio, same housing and feeding conditions and genetic background. Group 1 (PC) received 800 ppm chlorotetracycline in the feed over 8 consecutive days plus a single IM injection of a placebo (isotonic saline) at d0 (start of the trial, n=82). Group 2 (M) received 800 ppm chlorotetracycline in the teed over 8 consecutive days plus a single IM injection of 0.4 mg/kg bodyweight meloxicam (METACAM® 2%, Boehringer Ingelheim GmbH) at d0 (n=80). Clinical parameters were assessed as the daily Respiratory Score (RS), using a 3 point score (0=absence of signs to 3=abdominal breathing and disordered general condition) over 8 consecutive days and the total number of additional required injectable medications (AIM). Growth performance data for each group included the Average Daily Gain (ADG) for the following trial periods: d90 to d117, d117 to d170 (slaughtering), and d90 to d170 of age. Mortality was also calculated for these time periods. Slaughterhouse records per group, included the percentage of each lung surface (LS) affected by chronic and acute respiratory lesions.
[0073] Student's t-Test and Pearson's Chi-Square Test were used for the consequent comparisons of means and frequencies between trial groups.
Results and Discussion
[0074] RS and AIM in the meloxicam group were significantly lower (p<0.05) compared to the control group. Same applies for LS affected by acute lesions (p<0.01), while no differences were observed for LS in chronic cases (Table 1).
[0000]
TABLE 1
RS, LS: Mean (SD); AIM number (%)
Treatment Group
PC
M
Significance
RS
0.70 (0.63) a
0.50 (0.51) b
p = 0.0289
AIM (%)
10/82 (12.2%) a
2/80 (2.5%) b
x 2 = 4.226
LS(chronic)
5.96 (2.28) a
5.91 (2.32) a
p = 0.893
LS (acute)
3.71 (1.81) a
2.64 (2.03) b
p = 0.0007
a,b Values in a row with different superscripts differ significantly
[0075] The analysis of growth performance data revealed significant differences between groups at d90 to d117 (p<0.05, Table 2).
[0000]
TABLE 2
ADG: Mean (SD)
Trial Period
Group
d90 to d117
d117 to d170
d90 to d170
PC
0.64 (0.09) a
0.89 (0.06) a
0.81 (0.03) a
M
0.67 (0.10) b
0.89 (0.06) a
0.82 (0.03) a
a,b Values in a column with different superscripts differ significantly (p < 0.05)
[0000]
TABLE 3
Mortality: Number of animals/group (%)
Trial Period
Group
d90 to d117
d117 to d170
d90 to d170
PC
6/82 (7.32%) a
1/76 (1.22%)
7/82 (8.54%)
M
0/80 (0.00%) b
1/80 (1.25%)
1/80 (1.25%)
a,b Values in a column with different superscripts differ significantly (p < 0.05)
[0076] Under the conditions of this study, the reduction of the prevalence of respiratory signs as well as the reduced overall number of required injectable antibiotic medications are indicative for the potent anti-inflammatory activity of meloxicam. The latter could become a valuable adjunctive measure, especially when respiratory distress is associated with remarkable reduction of the feed intake. The initial differences in growth performance and in mortality rate could be explained by the fact that meloxicam, when combined with proper antimicrobial medication, contributes to faster recovery from a respiratory inflammation and faster restoring of the distorted growth rate of affected animals. Further research on the evaluation of feed intake and the use of meloxicam in PRDC recurring episodes is required. | A method of treating or preventing a respiratory disease in a pig, the method comprising administering to the pig in need thereof an effective amount of meloxicam or a pharmaceutically acceptable salt thereof. | 0 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to absorbent products and, in particular, to absorbent products such as tampons and similar catamenial devices. More particularly, the present invention relates to tampons and other catamenial devices that reduce or inhibit the amount of bacteria within the vagina coming into contact with the catamenial device.
2. Description of the Prior Art
Menstrually occurring toxic shock syndrome (TSS), a multi-system disease associated with colonization by Staphylococcus aureus ( S. aureus ) bacteria, has been associated with the use of tampons during menstruation. It is believed that the disease is caused by toxic shock syndrome toxin-1 (TSST-1). This toxin has been found to have been produced by Staphylococcal strains isolated from menstrual TSS patients.
Staphylococci may be present in the vagina or in the nose or the throat or on the skin. The blood, desquamated tissue and other materials present in the vagina during menstruation are a culture medium for S. aureus and organisms symbiotic to Staphylococci. As the Staphylococci increase in number, toxins may be produced that are absorbed through the vaginal wall, potentially resulting in toxic shock syndrome.
There have been numerous attempts to address toxic shock syndrome through modifications to catamenial devices, and specifically, catamenial tampons.
U.S. Pat. No. 4,405,323 to Auerbach is directed to a tampon designed to eliminate the hazards of toxic shock syndrome and dysmenorrhea. The tampon has incorporated therein an antibacterial agent. The agent allegedly disperses on contact with body fluids and prevents development of the organisms that produce the toxins, which cause toxic shock syndrome. Among the antibacterial materials disclosed for use are povidone-iodine compound, mercury, zinc, penicillin, erythromycin and nitrofurazone.
Patent Cooperation Treaty Publication No. WO 86/05388 (published Sep. 25, 1986) to Kass provides that the inclusion of a salt of a nontoxic divalent cation in absorptive pads, e.g. catamenial tampons, inhibits production of toxic shock syndrome toxin-1 and other staphylococcal products during use of said absorptive pad. Suitable salts include those of magnesium, barium, calcium or strontium (preferred) or of other divalent cations such as zinc, manganese, copper, iron, nickel and the like.
In U.S. Pat. No. 4,374,522 to Olevsky, it is stated that patterns of use of catamenial tampons seem to indicate that high absorptive capacity with the concomitant extended period of use of certain tampons are factors that contribute to the formation of toxic shock syndrome. The patent provides a tampon made of conventional cellulosic materials, such as rayon fibers, which have been compressed into a bullet-shape with an open bottom surface sealed by a fluid impermeable sheet. The fluid impermeable bottom and the traditional bullet shaped pledget define a hollow core, central reservoir area, which serves as a reservoir for excess menstrual fluid.
U.S. Pat. No. 4,431,427 to Lefren et al. discloses menstrual tampons comprising physiologically safe, water-soluble acids in their monomeric, oligomeric or polymeric forms. Citric, glycolic, malic, tartaric and lactic acids are disclosed as being useful in the practice of the invention. The presence of one or more of the above-noted acids in a tampon is said to inhibit the growth of bacteria responsible for toxic shock. Where an acid is used in its polymeric form, the tampon may additionally include an enzyme to hydrolyze the polymeric acid to its monomeric form.
Canadian Patent No. 1,123,155 to Sipos discloses a catamenial tampon for preventing toxic shock syndrome during menstrual flow. The body of the tampon, which is open at the insertion end and is closed at the withdrawal end, is snugly surrounded in its expanded condition by a fluid proof, thin and flexible membrane. This membrane, which can be made of polyethylene sheet, is biased against the vaginal wall during use of the tampon, is neutral to the vaginal mucosa and is completely impermeable to bacteria, viruses and toxic decomposition products of the menstrual flow.
Canadian Patent No. 1,192,701 to Bardhan discloses a tampon for the absorption of menstrual flow. The tampon comprises an inner layer of liquid-absorbent material and an outer layer, which surrounds and encloses the inner layer. Menstrual discharge may flow inwardly to the inner layer, but the outer layer is impervious to the passage of menstrual fluid outwardly from the inner layer. A plurality of liquid absorbent wicks extending from the inner layer through apertures formed in the outer layer serve as conduits for the flow of menstrual discharge from outside the tampon to the inner layer thereof. The disclosed structure allegedly minimizes the availability of discharge outside the tampon with a resulting reduction in the likelihood of growth of S. aureus and consequently its production of toxin. This patent also discloses that an antimicrobial compound, which is bactericidal or bacteriostatic to S. aureus , may be included in the inner layer. The antimicrobial agent may take the form of an antibiotic (such as penicillin, erythromycin, tetracycline or neomycin), a chemotherapeutic agent (such as a sulfonamide) or a disinfectant (such as phenol).
U.S. Pat. No. 4,585,792 to Jacob et al. discloses that L-ascorbic acid when topically applied to the vaginal area of a human female during manses will inactivate toxins known to contribute to Toxic Shock Syndrome. The ascorbic acid compound may be carried by a vaginal tampon. The disclosure of U.S. Pat. No. 4,722,937 is to the same effect.
U.S. Pat. No. 4,413,986 to Jacobs discloses a sterilely-packaged tampon assembly for sterile insertion of a tampon into the vagina and having a guide tube telescoped around an insertion tube and a flexible sheath attached to the inner end of the guide tube and tucked into the inner end of the insertion tube. In use, as the insertion tube is pushed through the guide tube and into the vagina, the flexible sheath is pulled over the inner end of the insertion tube and extends along the exterior thereof. The portion of the insertion tube, which is inserted into the vagina, is at all times fully sheathed by the flexible sheath.
U.S. Pat. Nos. 5,389,374, 5,547,985, 5,641,503, 5,679,369, 5,705,503, and 5,753,252, all to Brown-Skrobot et al., each disclose an absorbent product having a compound for inhibiting toxins produced by Staphylococcus aureus bacteria. The compound is selected from the group consisting of (1) monoesters of a polyhydric aliphatic alcohol and a fatty acid containing from eight to eighteen carbon atoms, in which the monoester has at least one hydroxyl group associated with its aliphatic alcohol residue, (2) diesters of a polyhydric aliphatic alcohol and a fatty acid containing from eight to eighteen carbon atoms, in which the diester has at least one hydroxyl group associated with its aliphatic alcohol residue, and (3) mixtures of the monoesters and diesters.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide an absorbent catamenial device or product, such as a tampon, that reduces or inhibits bacterial growth and toxin formation within the vagina.
It is another object of the present invention to provide a tampon that maximizes the effect of a desired amount of antibacterial agent in a tampon to reduce or inhibit bacterial growth in the vagina.
It is a further object of the present invention to provide a tampon that maximizes the effect of a desired amount of one or more finishing agents in a tampon to neutralize toxin formed in the vagina.
It is still a further object of the present invention to provide a method of incorporating the one or more antibacterial agents and the one or more finishing agents into a tampon.
The above and other objects and advantages of the present invention are fulfilled by a tampon or other similar catamenial device or product in which there is disposed an effective amount of antibacterial agent and finishing agent, capable of significantly reducing or inhibiting bacterial growth and neutralizing toxin within the vagina. Briefly stated, a broad feature of the present invention can be defined as a fibrous absorbent article for absorbing body fluids made up of a fibrous material defining a structure suitable for absorbing the body fluids, and disposed within the structure an effective amount, so as to reduce Staphylococcus aureus bacterial growth and neutralize TSS toxin-1 within the vagina, of one or more antimicrobial agents and one or more finishing agents.
DETAILED DESCRIPTION OF THE INVENTION
As used herein, the term “absorbent material” includes natural or synthetic fibers, nonwovens, films, foams, wood pulp, peat moss, superabsorbent polymers and the like, which are capable, either inherently or by virtue of the manner in which they have been assembled, of absorbing liquids such as water, urine, menstrual fluids, blood, and wound exudates.
As used herein, the term “absorbent products” includes catamenial tampons, wound dressings, disposable diapers, sanitary napkins, other kinds of tampons, such as those intended for medical, surgical, dental and/or nasal use, and any other article or device for absorbing body fluids therein.
In accordance with the invention, the absorbent product contains an amount of one or more antibacterial agents effective to reduce or inhibit the growth of S. aureus bacteria, when exposed to the absorbent product. In addition, the absorbent product has an amount of one or more finishing agents effective to neutralize TSST-1, which may have formed within the vagina when exposed to the Staphylococci.
In a preferred embodiment of the present invention, an amount of antibacterial agent and finishing agent is disposed in an absorbent product. It has been found that by disposing both the one or more antibacterial agents and the one or more finishing agents in an absorbent product, S. aureus bacteria growth and TSST-1 are significantly reduced as a result of the synergy between the neutralization effect of the one or more finishing agents and the bactericidal or bacteriostatic effect of the one or more antibacterial agents.
Preferably, the absorbent product is a tampon. The tampon may be made of any material known in the art to be suitable for insertion into the body and/or the absorption of body fluids. Typically, the tampon may be made of a fibrous material, such as cotton or rayon, a superabsorbent, or mixtures thereof.
Suitable antibacterial agents that may be included in the tampon, which effectively reduce S. aureus bacteria growth, include, without limitation, one or more quaternary ammonium compounds, glyceryl monolaurate, 5-chloro-2-(2,4-dichlorophenoxy)-2,4,4′-trichloro-2′-hydroxy diphenyl ether (triclosan), p-chloro-m-xylenol, N-(4-chlorophenyl)-N′-(3,4-dichlorophenyl) urea (triclocarban), 2-N-octyl-4-isothiazolin-3-one, iodine-based compounds, such as, for example, PVP-iodine, iodopropynyl butyl carbamate (glycacil), or diiodomethyltolylsulfone (amical), and any mixtures thereof.
It has been found that an absorbent product, such as a tampon, having one or more antibacterial agents present in an amount from about 0.01 percentage by weight (wt. %) to about 5 wt. %, based on the total weight of the tampon, is effective at significantly reducing the growth of S. aureus bacteria that comes into contact with the tampon.
Preferably, the one or more antibacterial agents are quaternary ammonium compounds conforming to the chemical structure:
where X is selected from the group consisting of: a halogen and a saccharinate; R 1 and R 3 is a straight or branched C 1 -C 4 alkyl; R 2 is a straight or branched C 6 -C 22 alkyl; and R 4 is of the chemical structure:
where R 5 is selected from the group consisting of: H, a straight or branched C 1 -C 4 alkyl, and a halogen.
Preferably, the quaternary ammonium compound is, for example, alkyl dimethyl benzylammonium chloride, alkyl dimethyl ethylbenzylammonium chloride, myristyl dimethyl benzylammonium chloride, lauryl dimethyl ethylbenzylammonium chloride, alkyl dimethyl benzylammonium bromide, alkyl dimethyl benzylammonium cetyl phosphate, alkyl dimethyl benzylammonium saccharinate, or any mixtures thereof.
In a preferred embodiment of the present invention, a mixture of alkyl dimethyl benzylammonium chloride and alkyl dimethyl ethylbenzylammonium chloride, sold under the trade name BTC 2125®M by Stepan Company, is used. It is present in the tampon in an amount from about 0.01 wt. % to about 5 wt. %. More preferably, the BTC 2125®M is present in an amount from about 0.10 wt. % to about 2.5 wt. %. In the most preferred embodiment, BTC 2125®M is present in an amount from about 1.0 wt. % based on the total weight of the tampon.
Suitable finishing agents that may be included in the tampon that neutralize toxins, such as TSST-1, include, for example, one or more surfactants. Suitable surfactants that may be included in the tampon to neutralize TSST-1, may include, without limitation, one or more nonionic, anionic, cationic, amphoteric, or any mixtures thereof.
Preferably, the one or more surfactants are nonionic surfactants. Suitable nonionic surfactants may include, for example, one or more alcohol ethoxylates, alkylphenol ethoxylates, amine oxides, carboxylic acid esters, ethoxylated anhydrosorbital esters, glycerol esters, poly(oxyethylene-co-oxypropylene) based surfactants, polyoxyethylene fatty acid amines, polyoxyethylene fatty acid esters, polyethylene glycol, polyethylene glycol esters, or any mixtures thereof.
Suitable cationic surfactants for use in the tampon include, for example, cocamidopropyl PG dimonium chloride.
Suitable amphoteric surfactants for use in the tampon include, for example, cocamidopropyl betaine, oleamidopropyl betaines, coco-betaine, disodium cocoamphodiacetate, or any mixtures thereof.
It has been found that an absorbent product, such as a tampon, having one or more finishing agents present in an amount from about 0.01 wt. % to about 10 wt. %, based on the total weight of the tampon, is effective at significantly neutralizing toxins that come into contact with the tampon.
The preferred surfactants are a polyoxyethylene fatty acid ester, such as, for example, polysorbate-20 and an amine oxide, such as, for example, cocamidopropyl amine oxide. Most preferably, the surfactant is polysorbate-20 sold under the trade name Tween®-20. Preferably, Tween-20 is present in the tampon in an amount from about 0.01 wt. % to about 10 wt. %. More preferably, Tween®-20 is present in an amount from about 1 wt. % and about 5 wt. %. In the most preferred embodiment of the present invention, Tween®-20 is present at about 2.5 wt. % based on the total weight of the tampon.
The absorbent products of the present invention may also include one or more additional components. These components may be one or more preservatives, deodorants, lubricants, fragrances, malodor counteractant odor absorbing and neutralizing materials, humectants (moisturizers), or any combinations thereof.
Tampons were prepared with varying concentrations of BTC 2125®M and Tween®-20. S. aureus MN8 was incubated with these tampons, and also on tampons without antibacterial agent and surfactant. After a predetermined incubation time, the concentration of both S. aureus and TSST-1 on the tampons was measured. The results of this study are summarized in Table 1 below.
TABLE 1
Growth of S. Aureus MN8 and Production of TSST-1
When Incubated with Tampons having BTC 2125 ® M and Tween ®-20.
AIR
AVERAGE
APPLICATOR
VOLUME
INOCULUM
TSST-1
TSST-1
DESCRIPTION
(cc)
(cc)
FINAL pH
CFU/ml
AVERAGE
(ng/ml)
(ng/ml)
Tampon with 0.25% BTC
5.7
8.7
6.65
3.6 × 10 4
7.7 × 10 3
200.5
332.28
and 0.25% Tween 20
5.9
7.7
6.71
2.0 × 10 2
159.1
Std. = 206.29
5.6
8.0
6.86
<100
227.8
5.5
6.9
6.79
<100
725.0
5.4
8.3
6.80
2.3 × 10 3
349.0
Tampon with 0.25% BTC
4.8
10.7
6.81
2.3 × 10 5
3.2 × 10 5
43.1
47.1
and 2.5% Tween 20
5.4
12.5
6.82
5.5 × 10 5
52.7
Std. = 10 76
5.3
10.5
6.82
1.7 × 10 4
65.8
5.0
10.4
6.81
6 5 × 10 5
40.6
5.4
10.4
6.83
1.7 × 10 5
35.1
Tampon with 1.0% BTC
4.7
8.3
7.06
<100
<100
267.69
382.64
and 0.25% Tween 20
4.9
7.4
6.96
<100
787.2
Std. = 236.02
5.3
8.6
6.92
<100
177.26
5.0
8.3
6.92
<100
507.74
5.0
8.4
7.04
<100
173.32
Tampon with 1.0% BTC
5.4
12.9
7.05
<100
<100
0.97
17.18
and 2.5% Tween 20
5.3
11.5
6.94
<100
30.07
Std. = 18.23
4.9
11.1
6.99
<100
6.12
5.5
11.6
7.04
<100
1.96
6.0
11.4
6.97
<100
46.81
Innoculum Control
4.0
10.0
6.37
1.3 × 10 9
1.4 × 10 9
482.86
440.09
4.0
10.0
6.38
1.3 × 10 9
477.79
Std. = 60.62
4.0
10.0
6.39
1.6 × 10 9
480.07
4.0
10.0
6.37
1.5 × 10 9
323.88
4.0
10.0
6.37
1.4 × 10 9
435.96
Starting load of S. aureus MN8: 1.6 × 10 6 CFU/ml, incubated @35° C. ± 2C for 22 hours.
As demonstrated by this data, it has been found that tampons with 1.0 wt. % BTC 2125®M and 2.5 wt. % Tween®-20 significantly reduced the growth of S. aureus , as compared to the innoculum control, by greater than 7 logs from the average of 1.4×10 9 CFU/ml. The growth was reduced by greater than 4 logs from an initial bacterial load of 1.6×10 6 CFU/ml. In addition, the innoculum control average TSST-1 of 440.09 ng/ml was reduced by greater than 96% to an average of 17.18 ng/ml.
The antibacterial agent and/or the finishing agent may be incorporated in or on the surface of the absorbent article and/or fiber(s) of the present invention by any suitable process known in the art. Suitable processes may include, for example, spraying, rolling, saturating, extruding, printing, incorporating the antibacterial agent and/or finishing agent into a viscose solution prior to forming rayon fiber, applying the antibacterial agent and/or finishing agent to fibers prior to forming the absorbent article, or any combinations thereof.
Various modifications to the present invention may be made as will be apparent to those skilled in the art. Thus, it will be obvious to one of ordinary skill in the art that the foregoing description is merely illustrative of certain preferred embodiments of the present invention. | There is provided a fibrous absorbent article for absorbing body fluids made up of a fibrous material defining a structure suitable for absorbing the body fluids, and disposed within the structure an effective amount, so as to reduce Staphylococcus aureus bacterial growth and neutralize TSS toxin-1 within the vagina, of one or more antimicrobial agents and one or more finishing agents. | 0 |
FIELD OF THE INVENTION
The present invention relates to office equipment such as printers and copiers, and in particular relates to an apparatus for holding a stack of sheets, as would be used in a paper supply for such equipment.
BACKGROUND OF THE INVENTION AND DESCRIPTION OF THE PRIOR ART
U.S. Pat. No. 5,377,969 describes a feeding apparatus for drawing sheets from a stack of paper, as would be used in a printer or copier. A stack of sheets is held so that one side of the stack abuts a slanted surface, so that, viewed elevationally, the stack assumes a generally parallelogram shape. The slanted surface is exploited by rollers which engage the top sheet of the stack, to ensure that exactly one sheet is drawn at a time when the printer or copier is in use.
The present invention relates to a device for holding a stack of sheets in a parallelogram shape.
SUMMARY OF THE INVENTION
According to one aspect of the present invention, there is provided an apparatus useful in retaining a stack of sheets, comprising a plate for engaging an edge of the stack of sheets, and a mechanism for selectably positioning the plate in an upright position and a slanted position.
According to another aspect of the present invention there is provided a printing apparatus, comprising a paper tray for retaining a stack of sheets, a plate for engaging an edge of the stack of sheets and a mechanism for selectably positioning the plate in an upright position and a slanted position.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an elevational sectional view of a paper supply drawer, as used in a copier or printer, using the present invention.
FIG. 2 is a perspective view of a portion of the exterior of a printer, showing an embodiment of the present invention.
FIG. 3 is a perspective view of one embodiment of the present invention.
FIG. 4 is a perspective view of another embodiment of the present invention.
FIG. 5 is a perspective view of another embodiment of the present invention.
FIG. 6 is a perspective view showing an additional aspect of the present invention.
FIG. 7 is a simplified elevational view of a xerographic printer including the present invention.
In the above Figures, like numerals indicate functionally equivalent elements in various embodiments.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 is a sectional elevational view of a paper supply drawer, or tray, as would be found, for instance, in a printer, copier, or other office equipment, showing some essential features of the present invention. With most relevance to the present invention, the drawer 100 defines a slanted surface 102 , which is a generally flat surface disposed approximately 30 to 60 degrees from the vertical. As described above in the '969 patent, a certain type of paper feeding apparatus exploits such a slanted surface, and it is desirable that a paper stack, such as indicated in FIG. 1 as S, be disposed with one of its edges abutting such a slanted surface.
According to the illustrated embodiment, one edge of a paper stack S is caused to abut slanted surface 102 by the presence and action of a plate 10 in contact with an opposite side of the stack. When a stack S is initially placed in the drawer, with the typical vertical sides (such as when removed from a package), one side of the stack is in general contact with plate 10 , which is in a substantially vertical “upright position” as shown. After the stack S is loaded, the plate 10 is moved to a substantially slanted position as shown in phantom and indicated as 10 ′. When plate 10 ′ is in the second position, the opposite side of stack S is pushed against slanted surface 102 , and the stack S generally assumes a parallelogram shape, as shown.
Also shown in FIG. 1 is a lever 12 , which interacts with plate 10 , and is shown in a position which is consistent with plate 10 being in its upright position. Shown in phantom and indicated as 12 ′ is the lever in a position consistent with plate 10 ′ being in its second position. The various possible mechanical means by which lever 12 interacts with plate 10 will be discussed below.
FIG. 2 is a perspective view of a portion of some office equipment, such as a printer or copier, in which a paper supply drawer or tray such as 100 is used. As is familiar, such a drawer 100 can be slid in and out from the body of the machine so that paper can be re-supplied to the machine. According to this embodiment of the invention, lever 12 is shaped and located so that, when drawer 100 is pushed back into the machine, such as after loading a stack of paper therein, lever 12 contacts a “contact surface” of the machine and is thus pushed downward as the drawer 100 is closed. As the lever 12 is pushed down, through a mechanism of a type which will be described in detail below, plate 10 is caused to move from its upright position to its slanted position, as described above. In turn, a stack of paper placed in the drawer 100 assumes the desired parallelogram shape and is pressed against the slanted surface 102 . In brief, pushing the drawer 100 in causes the stack S to assume the parallelogram shape. According to this aspect of the invention, the contact surface of a machine for this purpose can be an outer surface of the machine, as shown in FIG. 2, or can be on a member internal to the machine. Alternately, lever 12 can be in effect attached to a member within the body of the machine.
In order to provide the desired interaction between lever 12 and plate 10 , any number of types of mechanisms can be used. Below, certain mechanisms will be basically described, but it will be apparent that many variations can be made to the described mechanisms within the spirit and language of the claims.
FIG. 3 is a perspective view of one embodiment of the present invention. In this embodiment, plate 10 is movable between and upright position and a slanted position, as shown. Plate 10 assumes its slanted position when lever 12 , which is pivotably mounted relative to a main portion 16 of a mechanism which supports plate 10 in a particular position, is in a down position (as opposed to the up position, such as shown in FIG. 2 ). The mechanism includes at least one camming surface, such as 18 , which in effect transfers the motion of the downward positioning of lever 12 to move the plate 10 to its slanted position. When the lever 12 is pulled up again, the plate 10 returns to an upright position, either through the action of another camming surface, or of springs associated with the mechanism (not shown).
FIG. 4 is a perspective view of an alternate embodiment of the present invention. In this case, the plate 10 is once again caused to change position by the action of a lever 12 , but the lever 12 slides relative to the basic mechanism instead of pivoting. The member forming lever 12 slides along a bar 20 while a surface thereof engages a camming surface 22 associated with plate 10 . In this particular embodiment, when lever 12 is slid to the right in the Figure, the plate 10 is moved to its slanted position; when the lever 12 is slid to the left, plate 10 returns to an upright position, aided by spring 24 . Although a very simple mechanism is illustrated, many practical variations on the design can be contemplated to allow the sliding action of lever 12 and resulting positioning of plate 10 .
In the FIG. 4 embodiment, the lever 12 can be attached to or otherwise contact other surfaces (not shown) of the rest of a machine, to achieve the principle of “automatic” positioning of plate 10 to its slanted position when a paper tray or drawer is closed. The lever 12 can contact the outside of a machine, as largely shown in FIG. 2 above, or contact or be attached to a member within the body of the machine. In the FIG. 4 view, if the drawer and the attached mechanism including lever 12 is pushed to the left, the lever 12 will contact a surface of the machine, be pushed to the right, and therefore place plate 10 in its slanted position.
FIG. 5 is a perspective view of another possible embodiment of the present invention. Here, the plate 10 is more or less directly moved, such as by a user's hand, into a slanted position as needed, and a lever 12 , pivotably mounted on a surface (such as a main portion 16 as shown, or even a bottom surface of a paper tray or drawer), functions mainly as a “stop” to hold plate 10 in its slanted position. In this case, the “mechanism” for positioning plate 10 basically comprises the hinge on which plate 10 is mounted.
As is well known in the art of office equipment, a paper tray or drawer is typically provided with adjustable parts so that the tray can accommodate paper stock of various sizes. Returning to FIG. 1 above, it is desirable that the position of plate 10 in terms of distance to slanted surface 102 be adjustable so that a stack S of a range of sizes can be placed properly in the tray. To this end, there is provided means for adjusting the position of plate 10 , and such means can include a track 14 , which can be defined by a set of teeth or other structure in the body of tray 100 . The plate 10 and its associated mechanism moves along track 14 as needed to conform to a stack S of a given size.
FIG. 6 is a perspective view of another aspect of the present invention, what can generally be called a slidable mount for adjusting a position of the plate 10 , particularly relative to slanted surface 102 such as shown in FIG. 1. A catch 30 , which can be of any design, engages the teeth of track 14 to retain the plate 10 in a selected position relative to slanted surface 102 . Any basic design of such a slidable mount, generally familiar in the art, can be provided, with or without the illustrated teeth in track 14 . Another aspect of the invention is disposing the catch 30 or equivalent element underneath lever 12 when lever 12 is in a position consistent with plate 10 being in a slanted second position. The position of lever 12 thus makes catch 30 largely inaccessible, so that the position of plate 10 cannot be changed when the plate is in its slanted position.
Although the illustrations show plate 10 as a substantially solid plate with a flat surface, it will be appreciated that the plate 10 can be of any practical configuration, such as including openings, fingers, ridges, etc. as required to enhance performance.
FIG. 7 is a simplified elevational view of an office machine, in this case a xerographic or electrostatographic printer 200 (which may also function as part of a copier or facsimile machine) embodying the present invention. Sheets from a tray 100 are stacked in a parallelogram-shaped stack S by the action of plate 10 . Sheets are individually drawn by feed head 202 from stack S in a manner such as shown in the '969 patent, and sent through paper path 204 . Each sheet receives marking material forming an image from charge receptor 206 , and the marking material is fused in fuser 208 and deposited in tray 210 or other finishing device. | Certain designs of paper feeding devices used in copiers and printers require that an edge of a stack of sheets be in close contact with a slanted surface. An apparatus engages an opposite edge of the stack to urge the stack against the slanted surface, so that the stack assumes a parallelogram shape. The apparatus includes a plate which is movable from a vertical, upright position to a slanted position. Means are provided to cause the plate to move to the slanted position in response to the closing of a paper tray of a printer or copier. | 1 |
BACKGROUND
[0001] The present invention relates generally to medical care devices, and more particularly to devices for accurately and precisely dividing predetermined dosages of substantially solid medicines, whether in a tablet or capsule form.
[0002] Modern oral medicines come in a variety of forms depending on the desired effect, manufacturing abilities, shelf life, personal preference, and the like. Examples include tablets, capsules, liquids, gels, gums, and dissolving strips. Of these, tablets and capsules are the most widely accepted forms. Tablets may be defined as generally small, usually soluble masses of medicine, often held together with a binder. Capsules are similar, except capsule are usually substantially cylindrical shaped and comprise an outer coating or layer to hold the medication together.
[0003] Medications typically are produced in a limited number of concentrations or dosages. For example, a tablet may be produced in dosages of 150 and 250 mg active ingredient. Dosage variations for a particular medication may be driven by financial, manufacturing, and/or effectiveness considerations.
[0004] As medications are produced and delivered in predetermined dosages, patients may sometimes need to divide a medication into smaller portions in order to achieve a proper dosage as prescribed by a medical professional.
[0005] Further, some patients have difficulty swallowing larger tablets and capsules. Thus, some patients find it easier to divide a tablet or capsule medication into smaller, more easily swallowed portions, even where the full-sized tablet or capsule is the proper dosage for the patient.
[0006] The prior art is ripe with examples of various tablet dividers. However, a greater number of medications are being produced in capsule form. The tablet dividers of the prior art generally cannot consistently, properly, and accurately divide a medication in capsule form into smaller dosages.
[0007] Further, many more tablets are being produced with an outer shell which makes prior art medication dividers more difficult to use properly, as the outer shell may be difficult to pierce in order to divide the tablet as desired.
[0008] Thus, what is desired is a device for properly and accurately dividing tablet and capsule medications into small dosages.
SUMMARY
[0009] The various exemplary embodiments of the present invention include a device for dividing medications into smaller dosages. The device is comprised of a housing having a top section and a bottom section. A backend of the top section is connected to a backend of the bottom section via one or more hinges such that an underside portion of the top section is substantially adjacent to an upper-side portion of the bottom section when the one or more hinges are closed, and the upper-side portion of the bottom section is a substantially negative profile of the underside portion of the top section. The top section has one or more capsule loading ports, a first cutting blade, and a second cutting blade. Each capsule loading port has a substantially circular cross-section and is located on sides of the top section between the backside and a front end of the top section. The first cutting blade is substantially parallel and equidistant to the sides of the top section and connected to the top section via two or more flexible retaining means, such that the first cutting blade is in a start position as capsules are loaded into the one or more capsule loading ports, and the first cutting blade is in a second position when the first cutting blade is moved towards the underside portion of the top section and divides the capsules in the one or more capsule loading ports. The second cutting blade fixedly connected to the underside of the top section. The bottom section has two or more pill stabilizers and a medication storage area. The two or more pill stabilizer being for retention of medications to be divided by the second cutting blade when the one or more hinges are closed.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] The various exemplary embodiments of the present invention, which will become more apparent as the description proceeds, are described in the following detailed description in conjunction with the accompanying drawings, in which:
[0011] FIG. 1 is an illustration of side-perspective of an exemplary embodiment of the present invention.
[0012] FIG. 2 is an illustration of front view of an exemplary embodiment of the present invention.
[0013] FIG. 3 is an illustration of a top view of an exemplary embodiment of the present invention wherein the one or more hinges are open.
DETAILED DESCRIPTION
[0014] Various exemplary embodiments of the present invention are described herein and in the associated figures.
[0015] As shown in FIG. 1 , the various exemplary embodiments of the present invention include a device 10 for dividing preformed solid medications into smaller dosages.
[0016] The device is comprised of a top section 20 and a bottom section 30 . A backend 22 of the top section is connected to the backend 32 of the bottom section via one or more hinges 40 . It is preferred that when the one or more hinges are closed, an underside portion 25 of the top section is substantially adjacent to an upper-side 35 portion of the bottom section. Preferably, the upper-side portion of the bottom section is a substantially negative profile of the underside portion of the top section.
[0017] In addition to having a backend, the top section also comprises a front end 21 and sides 23 connecting the front end to the backend. The top section may be of any geometric shape, but preferably is rectangular in shape.
[0018] Likewise, the bottom section is comprised of a backend, a front end 31 and sides 33 connecting the front end to the backend. The bottom section may be of any geometric shape, but preferably is rectangular in shape. It is also preferred that the shape and size of the bottom section be substantially similar to that of the top section.
[0019] The top section is comprised of one or more capsule loading ports 50 , a first cutting blade 55 , and a second cutting blade 60 .
[0020] The one or more capsule loading ports of the various exemplary embodiments have a substantially circular cross-sectional shape. That is, when viewing the one or more capsule loading ports from the sides of the top section, the one or more capsule loading ports appear as circular-shaped holes in the side of the top section.
[0021] It is preferred that the one or more capsule loading ports extend substantially through the top section such that each of the one or more capsule loading ports are visible on each side of the top section. Thus, the top section, at least in a region comprising the one or more capsule loading ports, should be no more than slightly greater than the length of a medicine capsule.
[0022] In the various exemplary embodiments, each of the one more capsule loading ports may retain a single medicine capsule. In a preferred embodiment, the one or more capsule loading ports are all of the substantially identical predetermined size, that is, for example, the cross-sectional of each capsule loading port is of the same diameter.
[0023] In a more preferred embodiment, where there are multiple capsule loading ports, each capsule loading ports is of a different size than each of the other capsule loading ports of the device. For example, the device may include three capsule loading ports, each of a cross-sectional diameter of about 9 mm, about 7 mm, and about 6 mm.
[0024] The first cutting blade of the various exemplary embodiments of the present invention is connected to the top section. It is preferred that the first cutting blade of the exemplary embodiments is connected to the top section via two or more flexible retaining means 56 . The flexible retaining means are preferably attached to at least each of the ends of the first cutting blade.
[0025] In the various exemplary embodiments, the first cutting blade is substantially parallel to the one or more capsule loading ports, and preferably the first cutting blade is substantially equidistant from each of the sides of the top section. The first cutting blade is in a start position as medicine capsules are loaded into the one or more capsule loading ports. The first cutting blade is in a second position when the first cutting blade is moved towards the underside portion of the top section and thereby divides each of the capsules loaded into the one or more capsule loading ports. It is preferred that the first cutting blade not extend below the underside portion of the top section.
[0026] As the first cutting blade divides each of the capsules loaded into the one or more capsule loading ports, it is preferred that the capsules be divided into two substantially equal pieces.
[0027] It is also preferred that when the first cutting blade is in the second position, it is held in the second position via a fastening means 58 . The fastening means may be comprised of, for example, a latch, a hook, and the like.
[0028] In an exemplary embodiment, a retaining means may extend around the top section to retain the capsules loaded into the one or more capsule loading ports in the one or more capsule loading ports when the first cutting blade divides the capsules. Examples of such retaining means may be a rubber band, fabric, and the like.
[0029] The first cutting blade may be of any size, so long as it fits in the device. In a preferred embodiment, a blade depth of the first cutting blade is about 2 cm to about 10 cm.
[0030] In the various exemplary embodiments, the second cutting blade is fixedly connected to the underside portion of the top section of the device. The second cutting blade has a blade depth of about 1 cm to about 10 cm.
[0031] The second cutting blade is substantially parallel to the one or more capsule loading ports, and preferably the first cutting blade is substantially equidistant from each of the sides of the top section.
[0032] In an exemplary embodiment, one or more blade guards 62 are located on the underside of the top section to surround the second cutting blade. The one or more blade guards may extend outward and away from the second cutting blade starting from an end of the second cutting blade nearest to the backend of the top section, may extend inward and towards the second cutting blade starting from an end of the second cutting blade nearest to the backend of the top section, or a combination thereof.
[0033] In the various exemplary embodiments, the bottom section includes two or more pill stabilizers 64 . The pill stabilizers are located on the upper side of the bottom section of the device. The pill stabilizers may extend outward and away from the second cutting blade on the top section starting from an end of the second cutting blade nearest to the backend of the top section, may extend inward and towards the second cutting blade on the top section starting from an end of the second cutting blade nearest to the backend of the top section, or a combination thereof.
[0034] In a preferred embodiment, the one or more blade guards and the pill stabilizers are substantially the same shape such that when the one or more hinges are closed, the one or more blade guards rest substantially outside of or inside of the one or more pill stabilizers. See for example, FIG. 2 .
[0035] Medicines, in the form of tablets and pills may be placed in the upper side of the bottom section of the device and positioned between the one or more pill stabilizers. As the one or more hinges are closed, the second cutting blade is moved closer to the upper side of the bottom section and substantially divides the medicines positioned between the one or more pill stabilizers. It is preferred that the capsules be divided into two substantially equal pieces.
[0036] Upon closing of the one or more hinges, the underside portion top section may be maintained substantially against the upper-side portion of the bottom section via a locking means 68 . The locking means may be a latch, hook, or the like.
[0037] In various exemplary embodiments, the uppers-side of the bottom section may further comprise a concave pill crushing section 70 . The concave pill crushing section is preferably located substantially towards the backend of the bottom section.
[0038] In the various exemplary embodiments in which the bottom section comprises a concave pill crushing section, the underside of the top section further comprises a convex pill crushing section 75 that corresponds to and is substantially adjacent to the concave pill crushing section when the one or more hinges are closed.
[0039] In various exemplary embodiments, the upper-side of the bottom section may further comprise a storage area 80 .
[0040] While the invention has been described in conjunction with specific embodiments, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art in light of the foregoing description and examples, and without deviating from the contemplated scope of the present invention. Accordingly, it is intended to embrace all such alternatives, modifications and variations which fall within the spirit and scope of the appended claims. | The present invention is a device for cutting solid medications, whether in the form of capsules, tablets or pills. When cutting capsules, the capsules are retained to be divided by a first blade. Tablets and other forms of the medication are retained by pill stabilizers and cut by a second blade. The device also may have a pill crusher and a section to hold whole or divided medications. | 0 |
RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent application Ser. No. 12/427,257 filed Apr. 21, 2009, which is a continuation of U.S. patent application Ser. No. 11/257,198 filed Oct. 24, 2005, now U.S. Pat. No. 7,522,955 which is a continuation-in-part of U.S. patent application Ser. No. 11/004,392 filed Dec. 3, 2004, which is a continuation-in-part of U.S. patent application Ser. No. 10/955,173 filed Sep. 30, 2004, which claims priority of U.S. Provisional Patent Application Ser. No. 60/508,824 filed Oct. 3, 2003, which is incorporated herein by reference. This application is also a continuation of U.S. patent application Ser. No. 12/724,306 filed Mar. 15, 2010.
FIELD OF THE INVENTION
[0002] This invention relates to methods and apparatus for the ultrasonic cleaning of bodily tissues coated with biofilm and more particularly, to such method and apparatus employing irrigation of the biofilm and the application of ultrasonic energy to the biofilm.
BACKGROUND OF THE INVENTION
[0003] Bacteria may exist within a fluid media in a planktonic state or may form on a surface bounding the fluid medium in a conglomerate of microbial organisms termed a biofilm. In the biofilm, the bacteria live at a lower metabolic state than when in planktonic form and exude a hydrated matrix of exopolymers, typically polysaccharides, and other macromolecules. Bacteria in the biofilm form strong chemical bonds with surface carbohydrate moieties. The exopolymers encase the bacteria in a manner that leaves tunnels or channels through which the overlying fluid medium can circulate. In this way, the bacteria are protected from the dangers of the fluid medium, can receive nutrients, and rid themselves of waste. The protective film formed as part of a biofilm shields the bacteria from the action of antimicrobials and like therapeutic agents at concentrations which would otherwise normally affect the bacteria.
[0004] The bacteria in this unique metabolic state affect other bacteria in the region to produce a coordinated lifestyle. This process is termed “quorum sensing.”
[0005] Biofilms may be formed on the surface of any living tissue, as well as foreign bodies, such as heart valves and the like, which are maintained in association with human tissues. When the biofilm is formed on living tissue, the biochemical products and toxic wastes it secretes may affect the tissue surface to produce an inflammatory state and areas of chronic infection, such as chronic ear disease, osteomyelitis, chronic tonsillitis, prostatitis, vaginitis, and calculi, as in the kidney. In many cases, chronic sinusitis appears to be an inflammatory disease of the lining mucosal, rather than the disease of bacteria-invading tissue. I have conducted electron microscopic studies that show biofilm exists on the mucosal blanket overlying the cilia extending from sinus tissue. Collateral damage from the immune interaction between the biofilm products and the associated tissue would be the basis of the inflammatory mucositis seen in chronic rhinosinusitis.
[0006] The biofilm insulates the embedded bacteria from biocides contained in the proximal fluid layer so that normal concentrations of antibiotics or the like, which would kill the bacteria if they were in a planktonic state, have little or no effect on the bacteria of a biofilm. Antibiotic concentrations of 1000 to 2000 times higher than possible with systemic applied antibiotics would be required to destroy the bacteria of a biofilm.
[0007] Past efforts to disrupt the biofilm by breaking it up or killing the bacteria have included treatment with chemical compounds such as antibiotics, chemical agents directed at dissolving or breaking up the polysaccharide binders such as surfactants, enzymes, denaturing agents, and the like. In the dental field, the most effective treatment has been found to be scraping and debriding with mechanical instruments. Efforts have also been made to use ultrasonic energy to either increase the metabolic rate of the underlying bacteria so that they better absorb antibiotics and the like, or to mechanically disrupt the biofilm encasement by the mechanical bursting of micro-bubbles induced by ultrasonic energy sources. It has also been suggested that electric fields imposed across the biofilms or the fluid layers in contact with the biofilm will enhance break-up or electrophoretically drive biocides into the bacteria encased in the layers.
SUMMARY OF THE INVENTION
[0008] The present invention is accordingly directed toward a method of removing biofilms in general, and particularly from living tissue, and more particularly from body cavities that are coated with biofilm, by flowing fluid containing various biofilm-active agents against the biofilm and suctioning the fluid from the area. Simultaneously ultrasonic energy is applied to the biofilm either by a probe inserted into the fluid layer or by application through body tissues from a remote location. The fluid irrigation is introduced under pressure and withdrawn by a suctioning action to introduce the disruptive materials to the biofilm and the ultrasound produces shear forces which tend to tear off portions of the film and withdraw them from the treatment area.
[0009] This irrigation-suction action creates a fluid film over the biofilm and the ultrasonic energy acts to mechanically drive the fluid into the film and produce micro-bubbles in the fluid which release energy upon bursting and mechanically disrupt the fluid. Alternatively, the ultrasonic energy may increase bacterial metabolism leading to susceptibility to deranging protein synthesis or cell division. In certain embodiments of the invention which will subsequently be described in detail, this irrigation/suction accompanied by the introduction of ultrasonic energy into the resulting film may be accompanied by electric fields imposed across the biofilm or the fluid interfacing the biofilm and/or mechanical scrubbing, to further enhance the breakup of the biofilm.
[0010] These actions to disrupt the biofilm are all designed in such a way as to neither destroy nor unduly stress the underlying tissue. In an in vitro experiment sinus tissues covered by a mucus blanket harboring a biofilm were treated by irrigation and suction and ultrasonic energy was introduced by a probe immersed in the fluid layer covering the tissue. In another experiment the ultrasonic energy was introduced through the wall of the fluid container. In both cases the ultrasonic energy and irrigation shattered and removed the biofilm and the cilia growing from the tissue remained intact.
[0011] A preferred embodiment of the apparatus for practicing the present invention, which will subsequently be described in detail, comprises an elongated tube or barrel, adapted to be introduced to the human body through the nasal passages or otherwise, so that its distal end is in proximity to a biofilm-lined sinus to be treated. The tube may be rigid or flexible, straight or bent, and includes a first lumen for introducing pressurized bio-treatment fluid at the proximal end so that it passes through the tube and exits at the distal end. The discharge may be through a nozzle to produce a high-velocity spray. A second lumen is connected to a vacuum source at the proximal end so as to create a suction at the distal end to remove excess fluid along with debris, including fragments from the biofilm and secretions from the sinuses. Both the irrigation of the bio-affecting fluid and its suctioned removal may be continuous or intermittent, controlled by valves. This allows the introduction of fluid pressure waves by the alternate introduction of pressured fluid and its suctioned removal.
[0012] The distal section of the tube may be manually deformable to allow the surgeon to conform the tube to particular applications. This distal section may be removable from the main section of the apparatus to allow replacement with a sanitary, unbent section.
[0013] In an alternative embodiment of the invention the ultrasonic energy is introduced to the distal end of the application tube by introducing the ultrasound into the proximal end of the irrigating lumen so that the fluid column in the tube carries the ultrasonic forces to the treatment area, eliminating the need for an ultrasound horn formed along the length of the apparatus.
[0014] In an alternative embodiment of the invention, the biofilm affected tissue may be encased in a chamber having open resilient edges which bear against the tissue at its boundaries; the bio-affecting fluid is then introduced and removed from the chamber and ultrasonic forces are imposed on the fluid contained within the chamber, and bearing against the biofilm, either by a ultrasonic horn projecting into the fluid-filled cavity, or by the application of ultrasonic forces to the wall of the chamber.
[0015] The biofilm encasing chamber may either be formed at the end of an elongated tube containing the fluid lumens and the ultrasonic horn, or as a separate device which may be applied to external body parts, such as skin burns.
[0016] In still another embodiment of the invention the ultrasonic energy is introduced to the biofilm through the surrounding body structure by applying energy from an ultrasound probe into a body surface proximal to the biofilm, through a bag of fluid bearing against that surface. In treating sinusitis the probe may be positioned on the patient's face nearest the sinus being irrigated. The ultrasonic vibrations pass through the facial bones and tissue and stimulate the biofilm.
[0017] Other objectives, advantages and applications of the present invention will be made apparent by the following detailed description of several embodiments of the invention. The descriptions make reference to the accompanying drawings in which:
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] FIG. 1 is a perspective view of a handheld instrument, formed in accordance with the present invention, for practice of the inventive method;
[0019] FIG. 2 is a cross-sectional view of the tube of the handheld tool of FIG. 1 , taken along line 2 - 2 of FIG. 1 ;
[0020] FIG. 3 is a cross-sectional view of the device of FIG. 1 inserted into a living body cavity, with sections broken away to show the construction of the tube;
[0021] FIG. 4 is a cross-sectional view of an alternative embodiment of the apparatus of the present invention inserted into a living body cavity, and partially broken away to exhibit the electrodes used to impose an electrical field across the biofilm;
[0022] FIG. 5 is a cross-sectional view of another alternative embodiment of the apparatus of the present invention which includes a biofilm abrading device for imparting mechanical energy to the biofilm, supported at the distal end of the tube;
[0023] FIG. 6 is a cross-sectional view of an alternative embodiment of the apparatus of the present invention wherein the ultrasonic generator is disposed at the distal end of the instrument;
[0024] FIG. 7 is a view, partly in section, of an alternative form of the apparatus of the present invention including a cavity adapted to surround the treatment area;
[0025] FIG. 8 is another alternative embodiment of the apparatus of the present invention including a cavity adapted to surround the treatment area and having inlet and outlet ports for the bio-reducing agent and means for introducing ultrasonic energy through the wall of the cavity; and
[0026] FIG. 9 illustrates a method of treatment of a sinus to remove a biofilm in the mucosal blanket, wherein ultrasonic energy is introduced through the head from a facial probe while the sinus cavity is subjected to irrigation and suction via a probe inserted into the cavity.
DETAILED DESCRIPTION OF THE INVENTION
[0027] The method of the present invention broadly involves treatment of a body tissue or bodily implant or prosthesis having a biofilm coating on its surface by irrigating the surface with a flow of fluid and suctioning the excess fluid off while imparting energy to the biofilm directly or through the fluid to reduce or change the biofilm. The irrigating fluid preferably contains a bio-reducing agent which will reduce or disrupt the biofilm by destroying its integrity or damaging the constituent bacterial cells. These agents may include surfactants, proteases, enzymes, denaturing agents, and the like. They may include biocides such as antibiotics and antifungal agents.
[0028] The chemical agents which may disrupt and destroy the biofilm include guaifenesin, dornase alfa and N-acetylcysteine. These materials are particularly advantageously used in a preferred embodiment of the invention in which the biofilm and mucus coats the sinuses. Guaifenesin is a mucolytic and is often used for the treatment of sinusitis and rhinitis. Dornase alfa (ymogen) is used to treat the thick mucus of cystic fibrosis and N-acetylcysteine is used for excess mucus in chronic bronchitis. They are known to break up mucus which is involved in biofilm infections and may act on the biofilm itself. Thus, the use of these chemicals in the method of the present invention performs a synergistic role in simultaneously treating the underlying mucosal tissues and reducing the integrity of the overlying biofilm.
[0029] Any other bio-reducing or biocide drugs or combinations thereof may be used in a particular application.
[0030] The ultrasonic energy imparted into the fluid film covering the biofilm, in the practice of the present invention, may be of a sinusoidal or pulsed character. The ultrasonic signal is generated by a unit that is external of the body. The generator may be of a fixed frequency or it may scan a range of frequencies continually to ensure optimum coupling of energy through the fluid layer into the biofilm. The exact manner in which ultrasonic forces enhance destruction of biofilm may involve the physical agitation of the minute bubbles produced by the ultrasound in the overlying fluid. Bursting of these bubbles produces forces that may cause tears in the biofilm. Alternatively, the ultrasonic energy may increase the metabolism of the bacteria in the biofilm, increasing its susceptibility to the biocides and bio-reducing agents in the irrigating fluid. The energy of the ultrasound must be limited to avoid damage to the underlying tissues, and values as high as 250 watts per square centimeter are apparently safe.
[0031] This device is not designed to destroy mucosal tissue. Relatively low frequencies have been found more effective than higher frequencies in ultrasonic treatment of biofilm and 10 kHz-100 kHz may be a reasonable range of application. In in vitro experiments I have used 35 kHz successfully.
[0032] In those embodiments of the invention in which an electric field is applied across either the microfilm or the fluid layer overlying the microfilm, either AC or DC may be applied. The DC may be pulsed so that rapid changes in the field gradient induce tearing forces in the biofilm.
[0033] A preferred embodiment of an instrument for use in practice of the present invention is illustrated in FIG. 1 . The instrument, generally indicated at 10 , has a handle section 12 for manual support and manipulation of the device and an elongated application tube or barrel 14 extending from the handle and terminating in a distal end 16 . The tube 14 may be rigid and may be straight or formed with a bend along its length. Alternatively, it may be made of a manually, deformable material and may be bent as needed for application into a body cavity. The distal end of the tube 14 may be removable from the handle 12 for replacement.
[0034] A pair of conduits 18 extend along the handle and connect at their proximal end to a source of the bio-affecting irrigating fluid and to a sink for the suctioned fluid (not shown). The fluid is pumped outwardly from the proximal end from a source in one conduit and is then carried by the other conduit back from the irrigated source to the proximal end.
[0035] The pump which feeds the irrigating fluid to the instrument 10 and the suction device that retrieves it from the irrigated area may feed from the same sump with an appropriate filter in the return line to remove solid matter contained in the fluid. Alternatively, the fluid may not be reused and the irrigated fluid may be discarded. The two conduits 18 feed to lumens in the tube section 14 . As is best seen in the cross section of FIG. 2 , the irrigating fluid may pass through a lumen 20 which is concentric about the tube 14 along its length and return through a larger lumen 22 . An ultrasound horn 24 carries energy from a generator 50 ( FIG. 4 ) at the proximal end to the distal end.
[0036] When used for the treatment of rhinitis, the tube 14 is applied through the nasal cavity so that its proximal end is adjacent to the sinus area coated with biofilm to be treated. Irrigating fluid is then supplied through lumen 20 and withdrawn through lumen 22 at a suitable rate to maintain a fluid layer over the biofilm area. Ultrasonic energy may be applied through horn 24 to the fluid layer so that forces are imposed on the biofilm. Alternatively, in the embodiment of the invention illustrated in FIG. 9 , the ultrasound may be applied separately from the instrument 10 through the patient's body.
[0037] The irrigation produces shear forces which tend to tear the protruding sections of the biofilm away and the mechanical agitation produced by the ultrasonic energy enhances this tearing action. The bio-affecting agents in the circulating fluid also act on the biofilm so as to reduce or remove it. The process may require application of combined irrigation and ultrasound for an intended period, such as thirty minutes.
[0038] FIG. 3 illustrates the application of a preferred embodiment of the method of the present invention to a body cavity 30 such as the sinuses. A biofilm coating 32 extends over an infected area, releasing materials which inflame the underlying tissue. Irrigating fluid containing biocides and/or bio-reducing agents are introduced through the lumen 20 from a fluid source 46 and withdrawn from the larger area lumen 22 to a fluid sink 48 . Ultrasonic energy is introduced into the fluid film which results from the irrigation via the ultrasonic horn 24 from a generator 44 . The biofilm is acted on by the physical shearing forces imposed by the irrigation and suction; by the mechanical forces generated in the overlying fluid film from the ultrasound: and chemical action takes place as a result of the agents contained within the irrigating fluid. These factors reduce or completely eliminate the biofilm so as to free the inflamed area for application of antibiotics and the like which may be contained in the irrigating fluid or may be introduced separately following treatment with the irrigating fluid and ultrasound. The ultrasonic generator 44 provides the energy to the horn either at a set frequency or a scanned frequency or in pulses.
[0039] FIG. 4 illustrates an alternative embodiment of apparatus capable of imposing an electric field across the biofilm encoating the infected area and/or the fluid layer overlying the biofilm. The structure of the application tube is identical to the device in FIG. 1 with the exception that a pair of electrodes 40 and 42 extend down diametrically opposed sides of the tube from the proximal end to the distal end. At the proximal end they are connected to an electrical source 50 which generates a potential difference across the electrodes 40 and 42 . The applied voltage may be either direct current, either constant or pulsed, or alternating current of a fixed or scanned frequency. The application device also connects to a fluid source 46 , a fluid sink 48 , and an ultrasound generator 44 .
[0040] The electric field imposes phoretic forces on the biofilm and may drive the irrigating fluid into the biofilm to enhance disruptive action.
[0041] An embodiment of the invention illustrated in FIG. 5 applies mechanical forces to the biofilm through a brush or abrading device 60 . The device is either rotated or oscillated through a flexible shaft 62 which extends through the center of the rod 14 . At the proximal end it is driven by a drive member 64 . Irrigating fluid is provided through a line 66 from a sump to the lumen 20 of the tube 14 and is returned through the lumen 22 to the sump 68 through a filter 70 . Ultrasonic forces may also be applied through an ultrasonic horn driven by the generator 72 .
[0042] Alternatively, the ultrasonic forces could be applied to the proximal end of the fluid column formed in the lumen 20 so that the ultrasonic energy is carried to the distal end 16 by that column, eliminating the need for an ultrasonic horn. The transmission of ultrasonic forces throughout a fluid column is described in ULTRASONICS, VOL. 26, No. 1, 1988 at pages 27-30. The electric field applying electrodes 40 and 42 of the embodiment of FIG. 4 could also be combined with this unit.
[0043] In another alternative version of the instrument 10 , illustrated in FIG. 6 , rather than generating the ultrasonic vibrations at the proximal end and transmitting them through the instrument to the distal end, in the manner of the previously described embodiments, a piezoelectric generator 120 is supported at the distal end. Electric signals for powering the generator 120 are provided by a power source 122 , located at the proximal end of the instrument 10 , and carried to the generator 120 by wires 124 extending through the length of the instrument. This arrangement lightens the weight of the instrument and eliminates the attenuation of the ultrasonic waves which occurs during transmission along the body of the instrument.
[0044] The method of the present invention may also be employed on living body tissues that are easily accessible, such as the outer body covered by skin or the mucous membranes of the oral areas. FIG. 7 illustrates an alternative embodiment of the apparatus of the present invention which can be used to treat biofilms formed on these accessible areas. A typical application is to treat a burned portion of the skin over which a biofilm has formed. The apparatus illustrated in FIG. 7 is substantially identical to the embodiment of FIG. 1 except for the provision of a semispherical cavity 80 which is attached to the rod 14 adjacent its distal end 20 . The cavity has a central hole through which the distal end of the rod 14 passes so that the open end of the cavity extends beyond the distal end 20 . A resilient gasket 82 is formed about the open edge of the cavity 80 . By proper manipulation of the tube 14 the gasket may be pressed against an area of the skin to be treated to produce a closed containment volume 84 .
[0045] The irrigating flow of fluid containing a biocide or other bio-affecting agent from the rod end 14 fills the volume 84 with fluid. As additional fluid is introduced the surplus is sucked off through the second lumen of the rod 14 . Ultrasonic energy is then introduced into the fluid through the horn end 16 , causing forces to be imposed on the treatment area 86 bounding the volume 84 .
[0046] A variant of the apparatus used for the treatment of biofilms formed on exterior or otherwise accessible body tissues is illustrated in FIG. 8 . A semispherical chamber 92 with a resilient gasket 94 supported on its edge is brought into contact with a region 90 of the body which is coated with biofilm so as to define an enclosed volume 96 .
[0047] The volume 96 is irrigated by fluid following from an input tube 98 and exiting the volume 96 from an outlet tube 100 . The irrigating fluid contains biofilm affecting agents. The resulting fluid in the volume 96 is agitated by ultrasonic waves generated by piezoelectric transducers 102 and 104 spaced on the wall of the enclosure 92 and energized by appropriate electrical signals.
[0048] As has been noted, the ultrasonic energy may be introduced into the biofilm by means independent of the fluid flow generated by the irrigation apparatus. In the embodiment of the invention illustrated in FIG. 9 , a tube 110 is illustrated as being inserted into the nasal cavity of a human head, generally indicated at 112 , so that its distal end is adjacent the frontal sinus 114 . The tube 110 contains a pair of lumens for introducing under pressure, and removing under suction, an irrigating fluid, preferably containing a biofilm active agent which is the bio-reducing or biocide drug previously described, onto the mucosal surface covering the exterior of the frontal sinus. The biofilm has the mucosal surface as its substrate and it may become embedded within the mucosal surface.
[0049] Simultaneous with the irrigation of the mucosal surface overlying the frontal sinus cavity through the tube 110 , ultrasonic energy is introduced into the exterior of the head, proximal to the location of the frontal sinus, through a probe 116 connected to a transducer 118 . The probe 116 has a flexible, fluid-filled bag 119 supported on its end. The bag may be filled with a gel, water, or other fluid transparent to ultrasonic energy. The bag prevents skin on the head 112 from being burned by ultrasonic energy. It is positioned in pressured contact with the head to provide an efficient interface.
[0050] The transducer 118 is powered by an ultrasonic generator 120 . The power levels of the ultrasonic energy are preferably somewhat higher than those provided through the tube 110 , because of the attenuation of the energy by the skull bones. The ultrasonic energy reaches the mucosal layer on top of the frontal sinus 114 through the skull and cooperates with the irrigating fluid in a manner similar to the previously described embodiments of the invention.
[0051] Alternatively, the ultrasonic energy could be introduced at other locations on the interior of a nasal cavity adjacent to the sinus 114 . In the treatment of other biofilms formed at other locations within the human body, similar techniques may be used to provide the ultrasonic energy independent of the irrigating fluid. | To treat body surfaces, such as the sinuses, which are coated with biofilms, the surface is irrigated and suctioned with a fluid which may contain a biocide or other chemical agent for disrupting the biofilm while ultrasonic energy is applied to either the fluid barrier formed over the biofilm or a body surface proximal to the biofilm. Action of the fluid enhanced by the ultrasonic energy tends to remove sections of biofilm which are suctioned out of the site. An electrical field may also be applied to the biofilm to enhance the disruptive action. Apparatus for practicing this method to treat chronic rhinosinusitis comprises an elongated tube adapted to be inserted into sinus cavities through the nose or mouth. The tube includes a first lumen which feeds an irrigating fluid containing biocides and/or biofilm-disruptive chemicals to the treatment site and a second lumen which suctions fluid from the site. An ultrasound horn extends through the tube and its distal end introduces ultrasonic energy into the fluid layer overlying the biofilm. Alternatively, an ultrasound probe may be applied to an adjacent body surface, such as the face over a sinus cavity. In an alternative embodiment, the tube includes a pair of electrodes which establish an electric field across the biofilm, accelerating degradation. | 0 |
FIELD OF THE INVENTION
The present invention generally relates to therapy by spinal cord stimulation and more particularly relates to spinal cord stimulation for the treatment of orgasmic dysfunction.
BACKGROUND
Orgasmic dysfunction is an inhibition of the orgasmic phase of the sexual response cycle. Orgasmic dysfunction is a serious disorder that plagues both women and men. Like all dysfunctions, orgasmic dysfunction may be life long or acquired. The condition is referred to as primary (life-long) when the patient has never experienced orgasm through any means of stimulation. The problem is considered secondary (acquired) if the patient has attained orgasm is the past but is currently non-orgasmic. Situational orgasmic dysfunction in women refers to a woman who can climax through some methods of stimulation, but not through others. The American Psychiatric Association describes the disorder as the “persistent or recurrent delay in, or absence of, orgasm following a normal sexual excitement phase during sexual activity.”
The general theory of normal sexual response cycle involves three phases: desire, excitement, and orgasm. Metaphorically, each phase of the normal sexual response may be thought to have a common generator but each phase also has its own circuitry. This separate neural circuitry creates the possibility for separate and discrete inhibition of the three phases. Certain kinds of trauma, if sufficiently intense, disturb the entire system, but often only one component is disrupted.
Orgasmic dysfunction should be distinguished from the excitement phase of the sexual response cycle. The excitement phase involves the arousal or erection of the sexual organs. There currently are several products, both drug-induced and mechanical, to stimulate and induce the excitement phase.
For example, to treat impotence (also called erectile dysfunction) it is known to implant electrical conductors to the surface of the pelvic splanchnic nerve. Stimulation of this nerve with low voltage electrical pulses is believed to causes arterioles dilation and initiate erection. Also, it is known that implantation of an electrode on the cavernous nerves of a male, adjacent to his prostate gland, may also achieve penile erection. Further, other electrical impulse devices exist that are not implanted but instead applied topically to the coccyx region to promote sexual excitation. Impotence, however, should not be confused with orgasmic dysfunction where satisfactory erection may be obtained but there is an absence of orgasm.
Current treatment of orgasmic dysfunction concentrates on the psychological components of the disorder rather than the physiological components. Orgasmic dysfunction is a physical malady that results in marked distress and interpersonal difficulty. The physical disorder causes psychological performance anxiety and pressure. Sexual desire and frequency usually decline. The patient's intimate relationships ultimately suffer from resentment and conflict.
Although psychological therapy may be required to rebuild confidence and regain the phases of desire and excitement, the orgasm phase requires a physiological solution. A basic tenet of most sex therapies is that an actual physical response will alleviate much of the anxiety associated with the disorder and initiate a positive mental response regarding the other two stages of the sexual cycle. Although it is important in treatment to improve communication and enhance relationships, an initial objective in therapy is the ability to obtain orgasm under any circumstances.
Within the neuromodulating community, there is anecdotal evidence of patients who have experienced mild sensation of the genitalia while undergoing spinal cord stimulation for pain relief.
Spinal cord stimulation, on the other hand, has been used as a treatment for chronic painful conditions for approximately thirty years. Commonly, spinal cord stimulation is used to alleviate pain after failed surgery, pain due to neuropathies, or pain due to inadequate blood flow. Neurostimulation systems have been found to relieve chronic, intractable pain in the limbs or trunk.
The basic concept of neurostimulation as it relates to pain relief involves the substitution of sensations that reach the thalamus of the brain. Rather than a pain message, the spinal cord stimulation closes the gate in the spinal cord and replaces the pain sensation with a tingling sensation. Electrodes are positioned effectively to create parathesia in the painful area.
Parathesia refers to a change in sensation in an area of the body. Usually parathesia is used to show change in neurologic function caused by damage to a nerve or nerves. Parathesia is usually not an absence of sensation but a decrease or alteration of sensation. Patients have described parathesia as a “buzzing sensation.”
Parathesia is accomplished through the implantation of stimulating electrodes within the spinal canal. The electrodes are inserted between the vertebrae in parallel with the spinal cord. Low-voltage electrical stimulation is precisely applied to the spinal cord. Through direct stimulation of the dorsal column or the targeted peripheral nerve, the sensation of pain is replaced by a more pleasant “tingling” sensation.
The sensation can be adjusted in terms of amplitude to control intensity, pulse width to control duration and frequency. Further, the neurostimulation system is implantable in its entirety. Medtronic Neurological, a division of Medtronic, Inc. of Minneapolis, Minn. sells a neurostimulator system used for pain relief. The device has been approved by the Federal Drug Administration for implantation in the spinal cord to effectively alleviate pain.
Heretofore, spinal cord stimulation has not been used to treat orgasmic dysfunction. There exists a need, however, to effectively treat orgasmic dysfunction through a physiological approach.
SUMMARY
The present invention for the first time, recognizes that carefully placed and controlled spinal cord stimulation may be used to treat orgasmic dysfunction. Stimulating electrodes are placed in the spinal canal via a needle inserted between the appropriate vertebrae in parallel with the spinal cord. The electrodes are connected to a power source. Through variable transmission of radio frequency waves a patient suffering from orgasmic dysfunction may once again achieve orgasm.
The stimulator may be entirely implanted within the patient's body. The device is controllable in a variety of ways. Current stimulators for pain have the ability to vary according to a 24-hour clock. The device may be equipped with a controller operable by the patient. It is possible to program the device to deliver an arbitrarily limited number of stimulations of predetermined length to prevent overstimulation.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of the spinal cord stimulator implanted in a patient with a cut out sectional of the spinal cord.
FIG. 2 is a cross sectional view of a spinal cord; and
FIGS. 3 a and 3 b are fluoroscopic views of single and dual leads, respectively, in a patient's epidural space.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
The implantation of spinal cord systems is generally known and has a standard clinical procedure to effectuate pain relief. For example, the Medtronic Itrel and X-trel neurostimulation system for spinal cord stimulation is indicated for the management of chronic pain of the trunk or limbs. Also from Medtronic, the X-Tel and Matrix Receiver Model 3272 systems are also indicated for peripheral nerve stimulation and pain relief. With regard to the present invention however, the procedure differs in the indications for the implantation procedure and the electrode level on the vertebrae. The following represents a description sufficient to allow one skilled in the art to practice the invention. If needed for reference, the standard implantation procedure of neurostimulation systems is described in greater detail in the Spinal Cord Stimulation: Percutaneous Lead Implantation Guide , Medtronic, Inc. 1997, a clinical guide published by Medtronic Neurological, the disclosure of which is here incorporated by reference.
FIG. 1 illustrates the spinal cord stimulator as implanted in a patient with a cross sectional view of a spinal cord as is known in the art. The preferred system employs an implantable pulse generator 12 with insulated extensions to produce independent stimulation pulses which are sent to the spinal cord 20 through at least one insulated lead 14 that is coupled to the spinal cord 20 through electrodes located at point A. After implantation, an external controller 15 transmits signals through the patient's skin to the pulse generator 12 . The pulse generator 12 receives either radio frequency or magnetic influence from the external controller 15 and sends electrical impulses to the spinal cord 20 to control the patient's orgasm.
As seen in FIG. 2, the spinal cord is divided into specific neurological segments. The cervical spinal cord is divided into eight levels and contributes to different functions in the neck and arms. In the thoracic region the nerves of the spinal cord supply muscles of the chest. This region also contains nerves in the sympathetic nervous system. The lumbosacral spinal cord and nerves supply legs, pelvis and bowel and bladder.
The range of electrode placement may range between about the eighth thoracic level (T-8) and the third sacral level (S-3), inclusive of the lumbar vertebra levels. The entry level for this preferred range would therefore be at about the third lumbar level (L-3). If necessary, a caudal approach may be taken.
A more preferred range of electrode placement lies between about the eleventh thoracic level (T-11) and the second lumbar level (L-2). An entry level of the third lumbar level (L-3) would be preferable for this range. The exact position of the electrodes, however, is variable and unique among patients and is determined more precisely at the time of implantation.
The present invention is indicated by orgasmic dysfunction in either men or women.
A stimulating, insulated lead 14 is implanted into a patient's epidural space. As seen in FIGS. 3 a and 3 b , either single or dual leads may be placed within the epidural space as warranted by the individual patient's needs. At the tip of the lead 14 there are four electrodes 16 to carry electrical impulses. As outlined above, an entry level of approximately L-3 and a lead tip level in the range from about T-8 through S-3 are preferred. A lead level of T-11 through L-2 upon entry from L-3 is most preferred.
Upon placement, electrical stimulation should be supplied in an effective amount to achieve genital stimulation and orgasm. As used herein “effective amount” is variable among patients but generally corresponds within a rate range of approximately 2.1 to 130 pulses per second, a pulse width range of approximately 60 to 450 milliseconds, and an amplitude range of approximately up to 10 volts.
The testing lead position is tested to match a stimulation pattern and effective amount to the patient's orgasmic nerve distribution. As stated, the exact effective position of the electrodes is variable and unique among patients. The lead 14 is secured for trial screening of the patient's response to stimulation. A percutaneous extension is connected to the implanted and secured to the lead 14 and external percutaneous wires are connected. A patient then goes through a trial-screening period where the patient is evaluated in an awake and active state for stimulation effectiveness. Should the trial screening period prove ineffective the leads may be repositioned. Should the patient not wish to proceed, the leads and percutaneous extension may be removed. Should the trial screening period be positive (at least 50% effective and patient demonstrates desire to proceed), the spinal cord stimulation system is internalized within the patient.
For internalization, the percutaneous extension is removed. A neurostimulator 12 and an extension 18 for connection of the neurostimulator and the lead are then implanted. Preferably the neurostimulator 12 is implanted in the patient's abdomen. Thereafter, the spinal cord stimulation system is operative to induce orgasm upon activation of the neurostimulator.
The following represent examples of genital stimulation through spinal cord stimulation. It must be emphasized, however, that the exact effective position of the electrodes is variable and unique among patients and is determined more precisely at the time of implantation. For instance, Example 2 occurred when the electrode was initially inserted at an effective level for pain relief but became displaced over time to a point that induced genital stimulation.
Lead
#1
#2
Pulse
Placement
Lead
Lead
Rate
Width
Amplitude
T-11
Positive
Negative
100 pps
250 ms
0.4 V
The patient vocalized intense genital stimulation without discomfort.
EXAMPLE 2
Displacement
A patient had a spinal cord stimulator implanted for relief of left hip pain. The lead had become displaced and relocated at the T-11 level. The patient experienced genital stimulation rather than pain relief.
EXAMPLE 3
Prophetic
As stated, the necessary specifications of lead placement, rate, pulse width, and amplitude are variable among patients. Each patient must be tested for individual response among the above-stated variables.
For example, a patient may respond positively to lead placement at the T-8 level. The rate is set for 130 pulses per second, the pulse width is set at 60 milliseconds and the amplitude is set to 0.1 volts. Additionally, the patient may respond positively to S-3 placement with a rate of 2.1 pulses per second, a pulse width of 60 milliseconds, and amplitude of 10 volts.
Once the lead is placed, the patient should be subjected to a range of variables to determine the most appropriate. Each patient should also undergo a trial screening period to determine sustained effectiveness once the variables are set.
As a hypothetical example consider a 65-year-old female who suffers from obesity and is further troubled by traumatic avulsion of both the anterior and posterior cruciate ligaments of the left knee. Because of her body habitus and knee injury, she is unable to engage in sexual relations with her husband nor increase her metabolic rate to lose weight. She does desire to experience sexual climax. An initial stimulation site at the L2-3 level with lead 1 positive and lead 2 negative, a pulsewidth of 200 and a rate of 100 PPS may be inserted. The initial voltage level would be zero but would be increased incrementally in 0.10 V steps. Again, due to individual variables, sustained effectiveness should be appropriately tested and adjusted as necessary.
While the invention has been particularly shown and described with reference to a preferred embodiment thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention. | The present invention provides a method for spinal cord stimulation to treat orgasmic dysfunction. Stimulating electrodes are placed in the spinal canal via a needle inserted between the appropriate vertebrae in parallel with the spinal cord. The electrodes are connected to a power source. Through variable transmission of electrical signals a patient suffering from orgasmic dysfunction may once again achieve orgasm. | 0 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a Continuation-in-Part of and claims priority to US. Continuation-in-Part patent application No. 13/891,830, filed May 10, 2013, which claims priority to U.S. patent application Ser. No. 13/567,850, filed Aug. 6, 2012, which claims priority to U.S. Provisional Patent Application No. 61/515,855, filed Aug. 6, 2011; U.S. Provisional Patent Application No. 61/515,967, filed Aug. 7, 2011; U.S. Provisional Patent Application No. 61/521,653, filed Aug. 9, 2011; and U.S. Provisional Patent Application No. 61/525,760, filed Aug. 20, 2011.
BACKGROUND
[0002] Appropriate mixing during biological water, wastewater, and waste treatment can disperse microorganisms within the reactor and make the entire reactor volume active. Existing mixing methods for anaerobic and anoxic biological reactors include mechanical mixers and conventional air (or gas) mixers. Mechanical mixers have mechanical energy loss, and need more maintenance because it uses a motor to drive the impeller or propeller. In case of anaerobic digesters that need completely sealed tanks for the reaction, using a mechanical mixer is troublesome because the motor has to be outside of the tank, and there is a leaking potential at the mixer entry point. In some cases, mechanical mixing method could shear the highly active granular sludge or other added media that is used to aid the reaction. Conventional air (or gas) mixers use air or gas to mix the tank, and air or gas is continuously released to the tank. Air mixing is relatively mild. In addition, conventional air mixers can not be used to mix anaerobic or anoxic reactors for biological nutrient removal processes because a sufficient amount of oxygen can be transferred to the liquid to inhibit the reaction.
[0003] As a result, a preferred method to mix biological reactors needs to (a) effectively prevent particle accumulation at the bottom and/or on the top of the reactor; (b) not adversely impact the reaction by damaging the granular sludge or added media through shearing or by introducing inhibiting components, etc.; and (c) be simple to use.
[0004] Mechanical mixers inevitably have mechanical energy loss and also need regular maintenance. It may also negatively impact the reaction process by shearing or breaking the granular sludge or added media that is used to enhance the performance. On the other hand, regular air or gas mixing, although simple to use, does not have enough strength to prevent particle accumulation in a tank. If air is used, it may introduce oxygen to the tank, to inhibit anaerobic or anoxic biological reactions if these reactions are conducted within the tank. A new type of hydraulic mixing that is induced by gas (including air or biogas, or other gases), as long as it can provide a strong hydraulic force to prevent particle accumulation within the tank, will be a preferred method for mixing during the treatment of water, wastewater, organic waste, and in other biological processes.
[0005] FIG. 1 shows a conventional bioreactor. A mechanical mixer is used to mix the reactor contents. Under anaerobic condition, biogas may be produced. In this case, the tank is normally sealed and the biogas is collected as an energy source. However, for biological phosphorus removal process, the anaerobic reactor is used to cultivate phosphorus accumulating organisms (PAOs). In this case, the fermentation ends before the biogas production, and the tank is normally open to air. Under anoxic condition, the reactor is used to reduce nitrate and nitrite to form nitrogen gas, to remove nitrogen nutrient. The anoxic bioreactor is normally open to air. Nevertheless, conventional air mixing is not used for anaerobic or anoxic reactors, because oxygen in the air can transfer to the liquid in an amount that inhibits the anaerobic or anoxic reactions. In addition, conventional air mixing is too mild to mix the tank content.
[0006] FIG. 2 shows a conventional pre-anoxic process for biological nutrient removal. It has a continuously mixed anoxic zone for denitrification followed by a continuously aerated aerobic zone for organic matter degradation and nitrification. Mixed liquor in the aerobic zone is returned to the anoxic zone to provide nitrate, which is reduced to nitrogen gas within the anoxic zone. The effluent from the aerobic zone flows to a secondary clarifier for solids-liquid separation, and settled sludge in the secondary clarifier is returned to the anoxic zone to provide biomass needed for biological functions. The anoxic zone is normally continuously mixed using mechanical mixing devices.
[0007] FIG. 3 shows an airlift pump such as that disclosed in U.S. Pat. No. 6,162,020. It is driven by air, and can provide a strong, periodic lifting force to transfer water. During operation, the air is injected to the air chamber, and the air-water interface within the air chamber is pushed down gradually. Once the air-water interface reaches the elbow that connects the riser tube, the entire air volume within the air chamber is drown to the riser tube, creating an air plug within the riser tube. This air plug provides a strong force to lift water within the riser tube. This lifting action repeats, resulting periodic pumping action. Apparently this device can also be used to mix liquid if the outlet of the pump is submerged within the tank content. Compared to conventional airlift pumps, this device provides a significantly stronger hydraulic lifting and mixing intensity. Compared to the mechanical mixers, this mixer employs no mechanical moving parts, therefore is more energy efficient. However, the elbow that connects the air chamber and the riser tube could be easily clogged by debris contained in the wastewater during operation. Once clogged, cleaning the tube is very difficult because the top of the elbow is hidden within the air chamber, which is not readily accessible.
SUMMARY
[0008] The claimed technology is set forth in the claims below, and the following is not in any way to limit, define or otherwise establish the scope of legal protection.
[0009] One embodiment of the disclosed invention is a bioreactor apparatus and method that comprises one or more mixers that is driven by air or gas, providing a strong and periodic lifting force to mix or lift the reactor content. For convenience, this type of hydraulic mixing device is termed as surge lifting device or surge mixer herein. Optionally the disclosed bioreactor can be a section or a zone within a larger tank, or can be a separate tank. Baffles can be integrated into the bioreactor to create a static zone on the upper portion of the tank, to facilitate sludge settling and retention.
[0010] The disclosed bioreactor can optionally be operated under aerobic condition (with an additional aeration device) to perform organic matter degradation and nitrification, and the surge mixer is used to supplement the mixing of the aeration device if needed. For example, it can optionally be used to mix membrane bioreactor to reduce particle accumulation or fouling on the membrane surface. It can also be optionally used to mix other bioreactors packed with fixed media or moving media to remove the biofilm grown on the surface of the media. The disclosed bioreactor can optionally be operated under anoxic condition to perform denitrification. The anoxic bioreactor can optionally be placed before an aerobic zone or tank in a pre-anoxic process, and receive both influent and return mixed liquor from an aerobic zone or tank. The anoxic bioreactor can also be optionally placed after an aerobic zone or tank in a post-anoxic process. Optionally, multiple anoxic bioreactors can also be optionally placed before and after the aerobic zone or tank, to achieve more complete denitrification.
[0011] One example of the disclosed bioreactor can also be optionally operated under an anaerobic condition, used in conjunction with a down-stream aerobic zone, to culture PAOs for biological phosphorus removal. Optionally the disclosed anaerobic bioreactor can also be optionally used in conjunction with down-stream anoxic and aerobic bioreactors, to biologically remove organic pollutants, nitrogen and phosphorus.
[0012] In another example the disclosed anaerobic bioreactor can be used independently, to digest organic pollutants and solids. For example, it can be used to digest organic sludge and food waste to produce low molecular weight organic acids (acid-production step). This low molecular weight organic acids can be a carbon source for other biological reactions, such as, to enhance denitrification and biological phosphorus removal. It can also be used to complete the entire anaerobic process and produce methane gas. The methane gas produced within the anaerobic bioreactor can be collected as an energy source, and the entire bioreactor should be sealed. A biogas outlet may be installed at the top of the tank or in some other suitable locations. The biogas generated under the surge mixer within the bioreactor could drive the mixer automatically in another example. If this mixing frequency if not sufficient, the produced biogas can be recycled from the top of the tank back to the surge mixer to enhance mixing.
[0013] In other examples the disclosed bioreactors can also be modified by adding means to increase the sludge retention. For example, baffles can optionally be added on the upper portion of the reactor, to create a static zone before the tank content flows out of the tank. In this case, the content in the lower portion of the tank is recycled and mixed, while the upper portion of the tank serves as a sludge blanket filter or a clarifier.
[0014] The designs as the aforementioned bioreactors can be used for other applications, and different media can optionally be added to the reactor to enhance treatment. For example, plastic media or activated carbon (granular or powdered) can be added to the reactor, serving as the carrier of microorganisms. Membrane filter can also be used to retain biomass within the reactor. The hydraulic mixing from the surge mixer does not shear the added media but can also provide enough mixing and prevent sludge or particle accumulation. Similarly, other media such as zero valent ion, and coagulants can be added to the reactor to perform desired physical-chemical reactions. Multiple media can also be used (for example, powered activated carbon+coagulants) to enhance the reactor performance. Through baffle installation, a clarification zone is integrated to the reactor, to perform reaction and clarification within the same tank.
[0015] Yet another embodiment of the disclosed invention is a surge lifting device. It is an apparatus to create large diameter gas bubbles within a riser tube to provide high lifting potential periodically. It includes a gas collection chamber and a means to transfer gas to the riser. The gas collection chamber collects gas to a certain volume before periodically discharging them into the riser tube. As a result, a large gas plug forms within the riser, forcing the liquid within the riser to move upward via the buoyant force. This surge lifting device can be used for mixing tank content (surge mixer) and transferring liquid or liquid-solid mixture (surge pump). It can also be used to dredge sediments in rivers or lakes, and for other pumping applications.
[0016] Further objects, embodiments, forms, benefits, aspects, features and advantages of the claimed technology may be obtained from the description, drawings, and claims provided herein.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] FIG. 1 is a flow diagram of a conventional anaerobic or anoxic bioreactor.
[0018] FIG. 2 is a flow diagram of a conventional pro-anoxic process.
[0019] FIG. 3 is a cross sectional view of an airlift pump from U.S. Pat. No. 6,162,020.
[0020] FIG. 4 is a cross sectional view of a bioreactor according to one embodiment of the disclosed invention.
[0021] FIG. 5 is a cross sectional view of a bioreactor according to one embodiment of the disclosed invention.
[0022] FIG. 6 is a cross sectional view of a bioreactor according to still another embodiment of the disclosed invention.
[0023] FIG. 7 is a cross sectional view of a bioreactor according to yet another embodiment of the disclosed invention.
[0024] FIG. 8 is a cross sectional view of a biological treatment method according to one embodiment of the disclosed invention.
[0025] FIG. 9 is a cross sectional view of a biological treatment method according to one embodiment of the disclosed invention.
[0026] FIG. 10 is a cross sectional view of a bioreactor according to another embodiment of the disclosed invention.
[0027] FIG. 11 is a cross sectional view of a biological treatment method according to another embodiment of the disclosed invention.
[0028] FIG. 12 is a cross sectional view of a reactor and lift device according to one embodiment of the disclosed invention.
[0029] FIG. 13 is a cross sectional view of a reactor and lift device according to one embodiment of the disclosed invention.
[0030] FIG. 14 is a cross sectional view of a reactor and lift device according to another embodiment of the disclosed invention.
[0031] FIG. 15 is a cross sectional view of a liquid lift device according to an embodiment of the disclosed invention.
[0032] FIG. 16 is a cross sectional view of a liquid lift device according to another embodiment of the disclosed invention.
[0033] FIG. 17 is a cross sectional view of a liquid lift device according to yet another embodiment of the disclosed invention.
[0034] FIG. 18 is a cross sectional view of a liquid lift device according to still another embodiment of the disclosed invention.
[0035] FIG. 19 is a cross sectional view of a liquid lift device according to a further embodiment of the disclosed invention.
DESCRIPTION
[0036] For the purposes of promoting an understanding of the principles of the claimed technology and presenting its currently understood best mode of operation, reference will now be made to the embodiments illustrated in the drawings and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the claimed technology is thereby intended, with such alterations and further modifications in the illustrated device and such further applications of the principles of the claimed technology as illustrated therein being contemplated as would normally occur to one skilled in the art to which the claimed technology relates.
[0037] Appropriate mixing is extremely important for biological treatment of water, wastewater, and waste. Conventional mixing methods, including mechanical mixing devices or air mixing devices, are continuously operated. Mechanical mixing devices need regular maintenance and could shear particulate matter that is formed or added during the treatment, and continuous-flow air mixing devices provide only mild local mixing. Instead, a hydraulic surge mixing device that is driven by air or gas can provide a periodic strong lifting action appropriate for mixing biological and some physical-chemical reactors. In one embodiment the disclosed device is nearly maintenance-free (like the regular airlift pumps), and can provide sufficient mixing, and is energy efficient (no mechanical energy wasting). The disclosed devices reduce shearing of particulate matter added or formed within the reactor, and optionally do not add meaningful amounts of oxygen to the reactor to inhibit anaerobic and anoxic reactions during application. Use of a hydraulic surge mixing device according to the disclosed invention benefits the existing treatment processes for water, wastewater, and organic wastes by reducing energy use, reducing maintenance requirements, and improving treatment performance.
[0038] FIG. 4 illustrates a cross-sectional side view of one embodiment of the disclosed invention. This example can be used for physical, chemical, and/or biological reactions. If used for biological reactions, the reactor is normally called bioreactor. The bioreactor of this example includes a tank ( 10 ) that contains one or more hydraulic surge mixers ( 20 ). The hydraulic surge mixers can optionally be driven by air or other gases. It can optionally be operated under aerobic, anoxic, or anaerobic conditions, depending on the needs. For example, the bioreactor can be operated under aerobic condition (with an additional aeration device), and the surge mixer provides supplemental mixing to the reactor. When membrane or other media is used to increase the biomass concentration and improve the reactor performance, this supplemental mixing can help to reduce particulate or biofilm accumulation. It can also be used before an aerobic reactor to perform denitrification under anoxic condition (pre-anoxic process). In this case the mixed liquor from the aerobic reactor should be returned to the anoxic bioreactor. It can also be used after an aerobic reactor, to perform denitrification under anoxic condition (post-anoxic process), with or without external carbon addition. Air is an example gas to drive the surge mixer, which has negligible adverse effect to the denitrification reaction because of the limited oxygen transfer within the surge mixer. A bioreactor according to the disclosed invention can also be used before and after an aerobic reactor to perform more complete denitrification. In addition, it can also be used independently to perform denitrification reaction as long as the influent has nitrate, and there is a carbon source in the influent or added externally. It can also be placed ahead of an aerobic or anoxic reactor in a biological phosphorus removal process, to culture PAOs under anaerobic condition. In this case air is also a gas used to drive the surge mixer without noticeable adverse effect on the bioreactor performance. Likewise, other gas can also be use. If the influent is rich in organic matter (high strength organic wastewater, algae, organic sludge such as in wastewater sludge, kitchen waste, human and animal waste, etc.), the reactor can be operated as an anaerobic digester to produce low molecular weight organic matter such as fatty acids (before methane formation step) which can be used as a carbon source for biological nutrient removal processes to remove nitrate and phosphorus. It can also be used to produce biogas (to complete the methane formation step), and serve as a biogas generator. For biogas production, it is preferred that the tank ( 10 ) should be sealed from the atmosphere, with one or more gas collection ports installed on top of the tank to collect the biogas. The biogas produced directly under the surge mixer is naturally collected by the surge mixer. Once the collected biogas within the surge mixer's gas chamber reaches a certain volume, the biogas drives the mixer, resulting a spontaneous and periodic mixing process without any external energy input. If more frequent mixing is needed, the produced biogas can be recycled back to the gas chamber of the surge mixer using a gas recycle pump.
[0039] Because the surge mixer reduces shearing of granular particles, the granular sludge may be formed within the reactor during the operation. This granular sludge is a concentrated form of highly active microorganisms. It also has high density. As a result, extremely high concentration of the highly active biomass can be maintained within the reactor, to significantly improve the bioreactor performance. Water and wastewater treatment media such as plastic media and other porous media (granular or powered activated carbon, for example) that can retain microorganisms (through attachment growth) can optionally be added to the reactor to enhance the biodegradation. The added media can be dispersed within the tank, and the surge mixer can effectively mix the media. The media can also be optionally packed above the surge mixer. In this case the surge flow can turn over the bed and mix the media, while reducing mechanical break up the media. Membrane filter(s) can also be used to retain microorganisms within the reactor, and the surge mixer can effectively remove the accumulated microorganisms on the membrane surface through strong surge action. The same or similar design in FIG. 4 can also be used for other purposes or in other industry. For example, it can be used in brewery industry to replace the existing reactors that use mechanical mixers. It can also be used in non-biological processes for water and wastewater treatment, by dispersing particulate reactants such as adsorbents (GAC, iron oxide, aluminum (hydr)oxide, etc.), oxidizing or reducing agents (such as zero valent ion), chemicals (such as alum), catalyzers (such as TiO 2 ), and the like within the tank. A combination of different media can also be used. For example, the coagulant and powered activated carbon combination can be used in some cases, to enhance the retention and biodegradation of some organic compounds that could be difficult to be removed otherwise.
[0040] FIG. 5 illustrates a cross-sectional side view of an alternative embodiment of the disclosed invention. Compared to FIG. 4 design, a baffle ( 18 ) is installed in the upper portion of the tank ( 16 ). When tank content is pumped out of the surge mixer ( 17 ) from the bottom of the reactor, it is re-directed back to the lower portion of the tank ( 16 ). Therefore, the upper portion of the tank ( 16 ), between the tank wall and the baffle, is under relatively static conditions. This static condition serves as a clarification zone for settling particles or thickening zone for sludge, which reduces the amount of sludge being washed out of the reactor, therefore retains more sludge within the reactor for needed reaction. In addition to the similar functions the FIG. 4 design can achieve, it can also be used as a solids-contact clarifier in some applications, to perform reaction and clarification within one tank. In addition, it can be used as an up-flow sludge blanket bed or filter to perform biodegradation and/or filtration, with improved influent distribution at the lower portion of the tank. For example, it can replace the primary clarifier in a biological nutrient removal process, to digest settled particles from the influent and produce low molecular weight soluble organic matter that is used as a carbon source needed for denitrification and/or biological phosphorus removal. This reactor can also be used to treat water or wastewater by adding activated carbon and/or other media, which forms a media blanket. The surge mixer improves the distribution of the water during its filtration through the media. This media blanket can retain both pollutants and microorganisms on the surface of the media, therefore enhances pollutant removal through adsorption, biodegradation, and other mechanisms.
[0041] FIG. 6 illustrates a cross-sectional side view of an alternative embodiment of the disclosed invention. Compared to FIG. 4 design, multiple 3-way conduits ( 23 ) are installed on top of the surge mixer ( 22 ), to redirect the flow from the top of the surge mixer ( 22 ) back to the lower portion of the tank ( 21 ). These conduits ( 23 ) function like the baffle ( 18 ) in FIG. 5 design. Other baffle design can be used, as long as it can maintain part of the tank static.
[0042] FIG. 7 illustrates a cross-sectional side view of another embodiment of the disclosed invention. The bioreactor of this invention has a mixing zone ( 123 ) that is mixed using one or more serge mixers ( 117 ), followed by an aeration zone ( 124 ), then by a static zone ( 125 ). The mixing zone ( 123 ), the aeration zone ( 124 ), and the static zone ( 125 ) can optionally be located in separate tanks. For mixing zone ( 123 ) shown in FIG. 7 , a baffle is installed to re-direct the surged liquid back to the lower portion of the mixing zone ( 123 ), and maintain a static condition at the upper portion of the mixing zone ( 123 ). This is used to retain as much biomass as possible for reaction, while making the lower portion of the mixing zone mixed. Highly active granular sludge may be formed in the mixing zone to further improve its performance. Other methods to retain biomass may be used (such as using three way pipes to maintain a static zone, and/or adding different types of media to improve solids retention). Influent flows into the lower portion of the mixing zone ( 123 ) where it mixes with established biomass within the mixing zone and/or that returned from the aeration zone ( 124 ) or static zone ( 125 ), to perform denitrification if the mixing zone is under an anoxic condition. If the mixing zone ( 123 ) is under partial or full anaerobic conditions, PAOs can also be cultured to uptake phosphorus in the following aeration zone ( 124 ).
[0043] The mixed liquor leaves the mixing zone ( 123 ) and enters the aeration zone ( 124 ) where organic matter is degraded and nitrification is performed if an appropriate sludge age is maintained. An aeration device ( 121 ) is used to impart oxygen to the aeration zone ( 124 ) for aerobic reactions. The aeration may optionally be controlled by the capacity of the aeration device, aerobic zone DO, ammonia concentration, or a combination thereof. If the aeration zone ( 124 ) is operated under a low DO, simultaneous nitrification and denitrification could occur within the aeration zone, to facilitate total nitrogen removal and oxygen recovery. In addition, the low DO and low nitrate in the return mixed liquor to the mixing zone ( 123 ) further enhances the denitrification performance of the mixing zone and may also make the mixing zone partially anaerobic, to cultivate phosphorus accumulating organisms (PAOs), therefore add biological phosphorus removal capability. As a result, low DO aeration results in less aeration energy use, and also improves nitrogen and phosphorus removal at the same time. An optional aerobic zone that is operated under a higher DO (>1 mg/L) can be added between the low-DO aeration zone ( 124 ) and static zone ( 125 ), to polish the low-DO mixed liquor by recharging oxygen before entering the static zone ( 125 ). This will facilitate the sludge settling within the static zone, and also further oxidize ammonia and improve biological phosphorus uptake. If this optional higher-DO aerobic zone is used, the sludge from the static zone ( 125 ) still return back to aeration zone ( 124 ) and/or mixing zone ( 123 ). If the sludge from the static zone ( 125 ) is directly returned to the mixing zone ( 123 ), the internal return of mixed liquor from the aeration zone ( 124 ) to the mixing zone ( 123 ) may be eliminated. No matter if the mixed liquor in the low-DO aeration zone ( 124 ) is returned to the mixing zone ( 123 ), this process has a no DO mixing stage, a low DO aeration stage, and high DO aeration stage, therefore can be termed as a 3-stage process.
[0044] The mixed liquor then flows to the static zone ( 125 ) through a conduit formed by a baffle group ( 119 ), or other conduits (such as pipes) that connect the aeration zone ( 124 ) and the static zone ( 125 ). The static zone ( 125 ) is used to settle biomass, and the settled biomass is returned back to aeration zone ( 124 ) or directly to the mixing zone ( 123 ) using mechanical or airlift pumps, shown as an airlift pump ( 120 ) in this particular embodiment due to its low head requirement. In particular, if a surge lifting device that could result in a pulsation action at the lower portion of the static zone ( 125 ) is used to return the settled sludge from the static zone ( 125 ), it could improve the sludge thickening within the static zone ( 125 ). If the sludge from the bottom of the static zone ( 125 ) is directly returned to the mixing zone ( 123 ), the mixed liquor return device ( 122 ) may be eliminated. If the bottom of the static zone ( 125 ) is open to the aeration zone ( 124 ) (in case both zones are in the same tank), settled sludge at the bottom of the static zone ( 125 ) can be automatically returned to the aeration zone ( 124 ) as a result of the air lifting force in the aeration zone ( 124 ), which creates a continuous return flow in the conduit connecting the aeration zone ( 124 ) to the lower portion of the static zone ( 125 ), to carry the settled biomass back to the aeration zone ( 124 ). In this case the sludge return device ( 120 ) may be eliminated. Sludge may be wasted from any zone.
[0045] A polishing clarifier can optionally be added after the static zone ( 125 ), to further remove solids carried out of the static zone ( 125 ). Normally, the solids carried out of the static zone ( 125 ) to the polishing clarifier have lower settling velocity. If part or all these lower-settling solids (e.g. lighter-weight solids) collected in the polishing clarifier are wasted, the static zone ( 125 ) and polishing clarifier combination can serve as a selector, to automatically retain heavier solid particles, including the granular sludge, within the bioreactor, and improve the reactor performance. Another aerobic zone can also be optionally added between the static zone ( 125 ) and the polishing clarifier, to recharge oxygen to the static zone effluent. This optional aerobic zone also breaks up any floating sludge carried out of the static zone ( 125 ), and facilitate sludge settling in the polishing clarifier. This aerobic zone may also facilitate biological phosphorus uptake and oxidation of residue ammonia if biomass is present. This optional aerobic zone can also be used to mix chemicals if chemicals are used to treat the static zone effluent. The settled solids from the polishing clarifier can also be optionally returned back to the mixing zone ( 123 ) and/or aeration zone ( 124 ).
[0046] If the static zone ( 125 ) is located in a separate tank, it is normally called a secondary clarifier. A sludge return device ( 120 ) should be used, to return settled sludge from the bottom of the static zone ( 125 ) to either the mixing zone ( 123 ) or the aeration zone ( 124 ). If the sludge is returned to the aeration zone ( 124 ), an internal mixed liquor return device ( 122 ) should not be eliminated. In this case the aeration zone ( 124 ) can also be called the aeration tank. The aeration zone ( 124 ) can be operated under a low DO, to improve energy efficiency and nutrient (nitrogen and phosphorus) removal. If low DO is maintained within the aeration zone ( 124 ), an aeration tank or zone that is operated under a higher DO (>1 mg/L) can optionally be added between the aeration zone ( 124 ) and the static zone ( 125 ), to polish the effluent from the aeration zone ( 124 ). The addition of this higher DO aeration tank or zone can facilitate secondary clarifier performance, ammonia oxidation, and phosphorus removal. No matter if this optional higher DO aeration tank or zone is used, the settled sludge from the static zone ( 125 ) should be returned back to the aeration zone ( 124 ) and/or mixing zone ( 123 ), using a pump device. Sludge may be wasted from any zones.
[0047] If the sludge from the static zone ( 125 ) is directly returned to the mixing zone ( 123 ), the internal return of mixed liquor from the aeration zone ( 124 ) to the mixing zone ( 123 ) may be eliminated. No matter if the mixed liquor in the low-DO aeration zone ( 124 ) is returned to the mixing zone ( 123 ), this process has a no DO mixing stage, a low DO aeration stage, and high DO aeration stage, therefore can be termed as a 3-stage process.
[0048] A polishing clarifier can optionally be added after the static zone ( 125 ), to further remove solids carried out of the static zone ( 125 ). Normally, the solids carried out of the static zone ( 125 ) to the polishing clarifier have lower settling velocity. If part or all these lower-settling solids (e.g. lighter-weight solids) collected in the polishing clarifier are wasted, the static zone ( 125 ) and polishing clarifier combination can serve as a selector, to automatically retain heavier solid particles, including the granular sludge, within the bioreactor, and improve the reactor performance. Another aerobic zone can also be optionally added between the static zone ( 125 ) and the polishing clarifier, to recharge oxygen to the static zone effluent. This optional aerobic zone also break up any floating sludge carried out of the static zone ( 125 ), and facilitate sludge settling in the polishing clarifier. This aerobic zone also facilitates biological phosphorus uptake and oxidation of residue ammonia. This optional aerobic zone can also be used to mix chemicals if chemicals are used to treat the static zone effluent. The settled solids from the polishing clarifier can also be optionally returned back to the mixing zone ( 123 ) and/or aeration zone ( 124 ).
[0049] Compared to other processes, bioreactors according to the disclosed invention use an energy-efficient surge mixer, driven by air and without any moving parts, to create periodic surge lifting action to mix the content within the mixing zone, therefore reduces the energy use and maintenance needs. It also create a condition that may form highly effective granular sludge to facilitate processes function. Moreover, if the optional baffle on the upper portion of the mixing zone is used, the baffle improves sludge retention within the mixing zone, therefore improves the anaerobic or anoxic reaction rate.
[0050] An additional mixing zone can optionally be placed ahead of the pre-anoxic mixing zone ( 123 ) to serve as an anaerobic mixing zone, and sludge from the static zone can be returned to either mixing zones or aerobic zone. Sludge return from the pre-anoxic mixing zone and from the aerobic zone may be needed, to allow the three reaction zones to be under anaerobic-anoxic-oxic conditions in series, and achieve both nitrogen removal and phosphorus removal. All mixings may be air-driven and can optionally perform surge lifting action. All return devices may also be air driven to simplify operation.
[0051] FIG. 8 illustrates a cross-sectional side view of another embodiment of the disclosed technology. Compared to FIG. 7 design, it adds mixing devices in the aerobic zone. Instead of maintaining continuous aerobic condition, the aeration device in zone ( 144 ) operates in a cycling on and off pattern, to create an alternating anoxic-oxic condition. Therefore, zone ( 144 ) is now called alternating aeration on/off zone. Influent enters the reactor mixing zone ( 143 ), and mixes with the content within the mixing zone and the return mixed liquor from the alternating aeration on/off zone ( 144 ) or static zone ( 145 ) by a surge mixer ( 137 ), which optionally uses 3-way conduits to maintain the upper portion of the mixing zone ( 143 ) static. Instead of using 3-way conduits, baffles can also be optionally used to maintain the upper portion of the mixing zone static. Other particular media may also be used to retain biomass within the mixing zone. The purpose of this front mixing zone is to enhance biological phosphorous removal and denitrification, and is operated under anaerobic and anoxic conditions, depending on the operation cycle of the aeration device ( 141 ). The tank content leaves the mixing zone ( 143 ) and enters the alternating aeration on/off zone ( 144 ), which is separated by a baffle ( 138 ). The mixing zone ( 143 ), alternating aeration on/off zone ( 144 ), and the static zone ( 145 ) could also be located in separate tanks for large flow applications.
[0052] The aeration device ( 141 ) in the alternating aeration on/off zone ( 144 ) is operated in a cycling on and off pattern for organic matter removal and nitrification when the aeration device is on, and for denitrification when the aeration device is off. The aeration can optionally be controlled by the capacity of the aeration device, DO and/or ammonia concentration within the aerobic zone. The mixing device ( 146 ) in the alternating aeration on/off zone ( 144 ) is operated at least during the aeration-off period to provide mixing. The mixing device ( 146 ) within the alternating aeration on/off zone shown in this design is a surge lifting device, but it can also be other types of mixing devices. When the alternating aeration on/off zone is under aerobic condition (the aeration device is on), the mixing zone ( 143 ) is likely under anoxic condition. When the alternating aeration on/off zone is operated in the anoxic condition (without aeration but with mixing), the mixing zone ( 143 ) may be under anaerobic condition because there is no dissolved oxygen in the return mixed liquor, and the nitrate concentration is also low due to the additional denitrification within the aeration on/off zone during the aeration off period. Therefore, this mixing zone ( 143 ) is operated under alternating anaerobic-anoxic condition, corresponding to the anoxic-oxic condition of the alternating aeration on/off zone ( 144 ). Through the mixing zone and the alternating aeration on/off zone combination, the reactor can achieve comprehensive nitrogen and phosphorus removal. The mixed liquor leaves the alternating aeration on/off zone ( 144 ) and enters the static zone ( 145 ). Sludge may be wasted from the alternating aeration on/off zone right before the aeration is stopped, to ensure the maximum phosphorus uptake by the sludge. An aerobic zone or tank that is continuously aerated can optionally be added between the alternating aeration on/off zone ( 144 ) and the static zone ( 145 ), to further improve the reactor performance. This aerobic zone can recharge oxygen to the mixed liquor exiting the alternating aeration on/off zone. This will help to improve the sludge settling characteristics within the static zone ( 145 ). In addition, some ammonia or organic nitrogen entering the alternating aeration on/off zone ( 144 ) during the aeration off period is not oxidized, therefore the added continuously aerated zone should be used to oxidize this fraction of ammonia or organic nitrogen before solid-liquid separation if low ammonia discharge limit is required. Moreover, during aeration off period, some phosphorus will release from the sludge. This continuously aerated zone is used to re-uptake the released phosphorus during the aeration off period. Sludge may be wasted from this continuous aeration zone, to ensure the maximum phosphorus uptake by the sludge.
[0053] Sludge solids settled to the bottom of the static zone ( 145 ) are returned to the alternating aeration on/off zone ( 144 ) through a pump ( 140 ), shown is an air lift pump (although other types of pumps may also be used). The sludge can also be optionally directly returned to the mixing zone ( 143 ). If the settled sludge in static zone ( 145 ) is directly returned to the mixing zone ( 143 ), the mixed liquor return device ( 142 ) may be limited. The sludge return pump ( 140 ) can also be a mechanical pump or a surge lift pump. Supernatant in the static zone ( 145 ) leaves the reactor as effluent, and an optional polishing clarifier can be used to treat the effluent from the static zone ( 145 ), to further remove solids carried out of the bioreactor. Normally, the solids carried out of the static zone ( 145 ) to the polishing clarifier have lower settling velocity. If part of all these lower-settling solids (e.g. lighter-weight solids) collected in the polishing clarifier are wasted, the static zone ( 145 ) and the polishing clarifier combination can serve as a selector, to automatically retain heavier solid particles, including the granular sludge, within the bioreactor, and improve the reactor performance. Another aerobic zone can also be optionally added between the static zone ( 145 ) and the polishing clarifier, to recharge oxygen to the static zone effluent. This optional aerobic zone can also break up any floating sludge carried out of the static zone ( 145 ), and facilitate sludge settling in the polishing clarifier. This optional aerobic zone also facilitates biological phosphorus uptake and oxidation of residue ammonia. This optional aerobic zone can also be used to mix chemicals if chemicals are used to treat the static zone effluent. The settled solids from the polishing clarifier can also be optionally wasted or returned back to the mixing zone or ( 143 ) and/or the alternating aeration on/off zone ( 144 ).
[0054] The mixing zone ( 143 ), alternating aeration on/off zone ( 144 ), and static zone ( 145 ) can also be optionally located in different tanks. A continuously aerated tank or zone can optionally be added between the alternating aeration on/off zone ( 144 ) and static zone ( 145 ), to facilitate sludge settling, ammonia and organic nitrogen oxidation, and phosphorus removal. Another polishing clarifier can optionally be added after the static zone ( 145 ) to further removal sludge, and sludge in this polishing clarifier can optionally be wasted, or be returned back to the mixing zone and/or alternating aeration on/off zone. An aerobic tank or zone can also be optionally added before this polishing clarifier, to improve the sludge settling performance within the polishing clarifier. This aerobic tank or zone also facilitates biological phosphorus uptake and oxidation of residue ammonia. This optional aerobic zone can also be used to mix chemicals if chemicals are used to treat the static zone effluent.
[0055] Compared to the embodiment shown in FIG. 7 , FIG. 8 has a cycling aeration on and off operation pattern in the alternating aeration on/off zone. The nitrate/nitrite in the alternating aeration on/off zone can be denitrified within the same zone during the aeration-off period. In addition, the preceding mixing zone ( 143 ) can be more easily maintained at an anaerobic condition during the aeration off period, as a result of the more complete denitrification of the mixed liquor within the alternating aeration on/off zone. Compared to conventional anaerobic-anoxic-oxic (A 2 O) process or the University of Cape Town (UCT) process that have three zones or tanks in the bioreactor, the present invention only has two zones or tanks and less return streams. Therefore, the present invention is easier to construct and operate. In addition, during the aeration-off period the entire alternating aeration on/off zone is under anoxic condition, therefore the nitrate/nitrite species can be completely denitrified, the final effluent should have a lower total nitrogen concentration than that from A 2 O and UCT processes. Ammonia and/or nitrate within the alternating aeration on/off zone ( 144 ) can optionally be used as an indicator to control the operation of the aeration device ( 141 ). Maintaining a low DO during the aeration period can save energy and promote sustainability for wastewater treatment.
[0056] FIG. 9 illustrates a cross-sectional side view of another embodiment in accordance with the disclosed technology. Compared to the FIG. 8 embodiment, it adds a continuously aerated aerobic zone ( 165 ) at the end of the alternating aeration on/off zone ( 164 ), to recharge oxygen to the mixed liquor, facilitating solid-liquid separation, complete nitrification, and biological phosphorus uptake. Sludge may be wasted from the aerobic zone ( 165 ). In addition, the solid-liquid separation is performed in a different tank, or a secondary clarifier ( 168 ). The settled sludge in the secondary clarifier is optionally returned to the mixing zone ( 163 ) through a sludge return pump ( 160 ), which could be any pump device including mechanical pump or airlift pump. In this case the mixed liquor return device ( 162 ) may be eliminated. The settled sludge can also be optionally returned to the alternating aeration on/off zone ( 164 ). Excess sludge can optionally be removed from the secondary clarifier ( 168 ) as shown in FIG. 9 .
[0057] An optional polishing clarifier can be added to further treat the effluent from the secondary clarifier ( 168 ). In this case the secondary clarifier ( 168 ) is used to maintain sludge mass in the reaction tank, and the polishing clarifier is used to collect light-weight solids, which are optionally wasted out of the process. This two clarifier combination will serve as a selector, to keep heavier particles, including the granular sludge, within the process, to improve the treatment performance. An aerobic tank or zone can also be optionally added between the secondary clarifier ( 168 ) and the polishing clarifier, to improve sludge removal, phosphorus removal, and ammonia removal. It can also be used to mix chemicals if chemicals are used to treat the effluent from the secondary clarifier ( 168 ).
[0058] FIG. 10 illustrates a cross-sectional side view of another embodiment in accordance with the disclosed technology. It comprises a sealed tank ( 191 ) and a surge mixer ( 193 ) that is designed to collect biogas under it. It also has an optional means to return biogas ( 192 ) from the top of the reactor vessel ( 191 ) to somewhere under the collar of the surge mixer ( 193 ), to increase the surge mixing frequency of the surge mixer ( 193 ). Side baffle(s) can also be optionally installed below the gas chamber of the surge mixer ( 193 ) to increase gas collection and improve the mixing. Baffle(s) can also be optionally installed on the upper portion of the tank, similar to that disclosed in FIG. 5 , to create a static zone and facilitate solids retention. In some cases the gas collection chamber of the surge mixer (also refers as gas collar of the surge mixer) is near the bottom of the reactor vessel ( 191 ), and the amount of gas automatically collected from the tank space below it is very minimal. Therefore, gas will should be returned from the top of the reactor vessel, to initiate the surge action for tank mixing.
[0059] FIG. 11 illustrates a cross-sectional side view of yet another embodiment in accordance with the disclosed technology. In addition to the components shown in FIG. 10 , FIG. 11 shows the side baffle ( 103 ) which is used to collect most gas generated bellow the gas collection collar. In addition, the surge mixer ( 102 ) is connected to the tank through a spring mechanism ( 104 ). This spring mechanism can also be optionally installed on the top of the surge mixer and against the top of the tank. Moreover, a force mitigation plate ( 105 ) is installed above the outlet of the surge lifting device ( 102 ), to reduce the impact of surge to the top of the reaction vessel ( 101 ). When the surge flow hit the mitigation plate ( 105 ), it will provide an impact to the entire surge mixer ( 102 ) and make it vibrate, enhancing the mixing.
[0060] FIG. 12 illustrates a cross-sectional side view of another embodiment in accordance with the disclosed technology. This particular embodiment shows an automatic surge mixing device ( 272 ) with a different design. Feed is introduced into the reactor via inlet ( 264 ). There it mixes with, and is consumed by, anaerobic bacteria which produce biogas. As gas bubbles generated under the gas collection collar they float upward, and are captured by the gas collection collar ( 268 ). The gas expands in volume until it reaches the bottom of the upper riser ( 272 ). At this point the gas flows through the gas conduit ( 274 ) created by the lower riser ( 276 ) extending over the upper riser ( 272 ), and into the upper riser ( 272 ). As the gas travels through the upper riser ( 272 ) it pulls solids from the bottom of the reactor and deposits them at the top, recycling the tank content therefore effectively mixing the reactor. Accumulated gas leaves the reactor via gas outlet ( 280 ). Effluent from the reactor leaves through the outlet ( 282 ), and the reactor can be drained through the drain ( 284 ). All of the optional components described in the discussion of FIGS. 10-11 may be included in this embodiment as well.
[0061] FIG. 13 illustrates a cross-sectional side view of one embodiment of an air- or gas-lift device to lift liquid and liquid mixtures (sludge, mud, oil, sediment, or particles in liquid). This embodiment collects and stores gas (could be air, biogas, or other gases) in the gas collection chamber ( 301 ) to a certain volume, then releases it through the T-shaped conduit ( 302 ) to the riser tube ( 300 ) at once, to form a large gas plug inside the riser tube ( 300 ) and create a strong lifting motion, pulling liquid content from the bottom to the top of the riser tube ( 300 ). If the gas is continuously supplied, this lifting motion repeats periodically. Therefore, this device is termed surge lifting device herein to differentiate it with conventional continuous flow airlift devices. It can also be called surge mixer if used for mixing, or surge pump if used for liquid transfer. Gas enters the gas collection chamber ( 301 ) through either an optional gas supply line ( 303 ) as shown or by rising from a source below the device (not shown). In some applications the housing of the gas collection chamber ( 301 ) or the bottom of the riser tube ( 300 ) can be further extended to other locations, to draw liquid from different places.
[0062] During operation, the gas is initially collected by and stored in the gas collection chamber ( 301 ). The volume of the gas expands and the gas-liquid interface moves downward. At some point the gas leaks to the riser tube through the conduit ( 302 ), shown as a T-shaped tube, causing an initial lift within the riser tube ( 300 ). This initial lift further pulls the entire volume of the gas within the gas collection chamber ( 301 ) into the riser tube ( 300 ) at once, creating a gas plug within the riser tube therefore a significant lifting action, e.g. surge lifting action. This surge lifting action pulls the tank content from the bottom of the riser tube and releases it to anywhere above the top. Therefore, this surge lifting device can optionally be used to transport liquid, liquid mixtures, sludge, particles in liquid, etc. from one location to another, and can also be used to perform tank mixing, or to simply generate large gas bubbles if desired.
[0063] Compared to a disclosed device shown in FIG. 3 , the embodiment shown in FIG. 13 employs a 3-way conduit rather than an elbow. This improvement significantly reduces the chance of clogging when it is used to mix or transport liquid that has debris. In case of clogging, FIG. 13 design is very easy to clean, because the top of the 3-way conduit is easily accessible. FIG. 14 illustrates a cross-sectional side view of an alternative embodiment of an air- or gas-lift type device to lift liquid and liquid mixtures (sludge, mud, oil, or particles in liquid). It has the same function as the FIG. 13 embodiment, but it has two 3-way conduits, which make it even less likely to be clogged. In case one of the conduit is clogged, the pump is still functional using the second 3-way conduit. Overtime, the clogged conduit will be gradually un-plugged either from the top or from the bottom of the clogged 3-way conduit through repeatedly pulling and pushing actions during the surge.
[0064] FIG. 15 illustrates a cross-sectional side view of an alternative embodiment of an air- or gas-lift type device to lift liquid and liquid mixtures (sludge, mud, oil, or particles in liquid). Compared to FIG. 14 embodiment, it uses baffles ( 332 ) to replace the 3-way conduits to achieve the same function. This design reduces the overall size of the device, and is easier to build. The low edge of the housing of the gas chamber ( 331 ) can be extended to other locations, to draw liquid from other places. The bottom of the riser tube ( 330 ) can also be extended to other locations.
[0065] FIG. 16 illustrates a cross-sectional side view of an alternative embodiment of an air- or gas-lift type device to lift liquid and liquid mixtures. Compared to FIG. 15 embodiment, a T-shaped pipe ( 344 ) is connected to the bottom of the riser tube. It is an example to extend the bottom of the riser tube, and can be used to increase the impact area when mixing function is used.
[0066] FIG. 17 illustrates a cross-sectional side view of another embodiment of an air- or gas-lift type device to lift liquid and liquid mixtures. Different from the early art disclosed in FIG. 3 , the riser tube in FIG. 17 design ( 350 ) has a closed bottom. It is actually connecting the riser tube with a U-shaped conduit at the bottom, therefore it is easy to build.
[0067] FIG. 18 illustrates a cross-sectional side view of another embodiment of an air- or gas-lift type device to lift liquid and liquid mixtures. It has the similar function as the embodiment shown in FIG. 17 . However, the housing of the air chamber ( 361 ) extends to a different direction. This is an example for how the housing can be extended to other places for all the surge lifting devices.
[0068] FIG. 19 illustrates a cross-sectional side view of another embodiment of an air- or gas-lift type device to lift liquid and liquid mixtures. It has the similar function as the embodiment shown in FIG. 13-18 . However, it uses a 3-way conduit ( 372 ) to transfer gas to the riser that has a closed bottom ( 370 ).
[0069] While the claimed technology has been illustrated and described in detail in the drawings and foregoing description, the same is to be considered as illustrative and not restrictive in character. It is understood that the embodiments have been shown and described in the foregoing specification in satisfaction of the best mode and enablement requirements. It is understood that one of ordinary skill in the art could readily make a nigh-infinite number of insubstantial changes and modifications to the above-described embodiments and that it would be impractical to attempt to describe all such embodiment variations in the present specification. Accordingly, it is understood that all changes and modifications that come within the spirit of the claimed technology are desired to be protected. | Described herein are methods and devices for treating water, wastewater, and organic wastes. The methods and devices are mixed by using hydraulic surge mixers. This surge mixer is driven by gas and can provide occasional surges of water using large bubbles which are able to move great volume of liquid while minimizing dissolved oxygen transfer to the surrounding liquid. Use of the devices and processes herein provides a simple, eloquent approach to water and wastewater treatment with less operation and maintenance costs than conventional devices and/or processes. The same surge lifting device can also be installed in other reactors to mix the tank content and enhance reaction with reduced energy use and maintenance needs. | 2 |
[0001] The present invention is in the field of medicinal chemistry. The invention relates specifically to compounds useful as opioid antagonists, methods of treatment, methods of using, and pharmaceutical compositions thereof.
BACKGROUND
[0002] Three types of opioid receptors, mu, kappa, and delta opioid receptors are generally reported. Recent evidence points to the interactions between receptor dimer combinations of mu, kappa and/or delta receptors (called heterodimers) as also contributing to opioid activity. Opiate receptors and their normal regulation or lack thereof, has been implicated in disease states including irritable bowel syndrome, nausea, vomiting, pruritic dermatoses, depression, smoking and alcohol addiction, sexual dysfunction, stroke and trauma in animals. Therefore it is not surprising that the ability to antagonistically bind opioid receptors has been shown to produce ameliorative, preventative and/or treatment effects in animals including humans afflicted with one or more of these disease states.
[0003] More recently, antagonists of the opioid receptors have been found to increase metabolic energy consumption, and reduction of weight in obese rats while maintaining muscle mass. These findings indicate that an effective opioid antagonist may be useful in preventing, treating and or ameliorating the effect of obesity. Considering the percentage of the population that is obese in Western societies and the indirect costs associated with treating the effects and symptoms of obesity and Related Diseases, the impact of these findings cannot be overstated.
[0004] Though many opioid antagonists have been disclosed, the search continues for alternative and/or improved or more effective antagonists having an overall benefit to the patient with little or no major side effects. U.S. Pat. No. 4,891,379 discloses phenylpiperidine opioid antagonists useful for the treatment of diabetes and obesity. Clinical development of a compound claimed in U.S. Pat. No. 4,191,771 was discontinued due to poor bioavalibility characteristics. Bicyclic analogs of phenyl piperidine have been prepared and reported as opioid antagonists by Wentland, et al., Biorganic and Medicinal Chemistry Letters 11 (2001) 623-626; see also Wentland, et al., Biorganic and Medicinal Chemistry Letters 11 (2001) 1717-1721. Finally, European Patent application number 1 072592A2 filed May 18, 2000, discloses phenylpiperidine compounds of formula I
wherein A, D, R 1 , R 2 , R 3 X, and n have meanings given in the description, which are useful in the prophylaxis and in the treatment of diseases mediated by opioid receptors such as pruritus.
[0006] Not withstanding these and other disclosures of compounds useful as opioid receptor antagonists, there remains an unmet medical need for safe, effective and/or alternate treatment or prophylaxis of diseases associated with opioid receptors, particularly obesity and Related Diseases.
SUMMARY OF THE INVENTION
[0007] The present invention relates to a compound of the formula (I)
or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomers or mixtures thereof.
[0008] The present invention also provides a method of using a compound of formula I for the prevention, treatment and/or amelioration of the symptoms of obesity and Related Diseases.
[0009] The present invention also provides a pharmaceutical formulation comprising a compound of formula I in association with a carrier, diluent and/or excipient.
[0010] The present invention provides a compound of formula I having improved efficacy and bio-availability compared to compounds disclosed in U.S. Pat. No. 4,891,379 and European Patent application EP 1,072,592 A2.
[0011] The present invention relates to the use of a compound of formula I for the treatment and/or prophylaxis of obesity and Related Diseases including eating disorders (bulima, anorexia nervosa, etc.), diabetes, diabetic complications, diabetic retinopathy, sexual/reproductive disorders, depression, anxiety, epileptic seizure, hypertension, cerebral hemorrhage, conjestive heart failure, sleeping disorders, atherosclerosis, rheumatoid arthritis, stroke, hyperlipidemia, hypertriglycemia, hyperglycemia, and hyperlipoproteinenamia, substance abuse, drug overdose, compulsive behavior disorders (such as paw licking in dog), addictive behaviors such as gambling.
[0012] The present invention provides a compound of formula (I) useful for the manufacture of a medicament for the treatment, prevention and/or amelioration of symptoms associated with obesity, Related Diseases.
[0013] The present invention provides a compound of formula I useful in the treatment of obesity and related diseases with reduced potential for inhibition of cytochrome P450 enzyme.
[0014] In another embodiment, the present invention provides a compound of formula I or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomers or mixtures thereof, useful as an appetite suppressant.
DETAILED DESCRIPTION OF THE INVENTION
[0015] The term “suitable solvent” refers to any solvent, or mixture of solvents, inert to the ongoing reaction that sufficiently solubilizes the reactants to afford a medium within which to effect the desired reaction.
[0016] The term “mutual solvent” means a solvent that is used to dissolve two or more components of a reaction or mixture separately prior to reaction or mixing, that is a solvent common to more than one reagents or components of a mixture.
[0017] As used herein, the term “patient” includes human and non-human animals such as companion animals (dogs and cats and the like) and livestock animals. Livestock animals are animals raised for food production. Ruminants or “cud-chewing” animals such as cows, bulls, heifers, steers, sheep, buffalo, bison, goats and antelopes are examples of livestock. Other examples of livestock include pigs and avians (poultry) such as chickens, ducks, turkeys and geese. Also included are exotic animals used in food production such as alligators, water buffalo and ratites (e.g., emu, rheas or ostriches).
[0018] The preferred patient of treatment or prevention is a human.
[0019] The terms “treating” and “treat”, as used herein, include their generally accepted meanings, i.e., preventing, prohibiting, restraining, alleviating, ameliorating, slowing, stopping, or reversing the progression or severity of a pathological condition, or sequela thereof, described herein.
[0020] The terms “preventing”, “prevention of”, “prophylaxis”, “prophylactic” and “prevent” are used herein interchangeably and refer to reducing the likelihood that the recipient of a compound of formula I will incur or develop any of the pathological conditions, or sequela thereof, described herein.
[0021] As used herein, the term “effective amount” means an amount of a compound of formula I that is sufficient for treating a condition, or detrimental effects thereof, herein described, or an amount of a compound of formula I that is sufficient for antagonizing the opioid receptors to achieve the objectives of the invention.
[0022] The term “pharmaceutically acceptable” is used herein as an adjective and means substantially non-deleterious to the recipient patient.
[0023] The term “formulation”, as in pharmaceutical formulation, or “pharmaceutical composition” is intended to encompass a product comprising the active ingredient (compound of formula I), and the inert ingredient(s) that make up the carrier, as well as any product which results, directly or indirectly, from combination, complexation or aggregation of any two or more of the ingredients, or from dissociation of one or more of the ingredients, or from other types of reactions or interactions of one or more of the ingredients. Accordingly, the pharmaceutical formulations of the present invention encompass any composition made by admixing a compound of the present invention and a pharmaceutical carrier, or a compound of the formula I and a pharmaceutically acceptable co-antagonist of opioid receptors useful for the treatment and/or prevention of obesity or Related Diseases where antagonism of opioid receptors may be beneficial.
[0024] The terms “obesity and Related Diseases” or “Related Diseases” as used herein refers to such symptoms, diseases or conditions caused by, exacerbated by, induced by or adjunct to the condition of being obese. Such diseases, conditions and/or symptoms include but are not limited to eating disorders (bulima, anorexia nervosa, etc.), diabetes, diabetic complications, diabetic retinopathy, sexual/reproductive disorders, depression, anxiety, epileptic seizure, hypertension, cerebral hemorrhage, congestive heart failure, sleeping disorders, atherosclerosis, rheumatoid arthritis, stroke, hyperlipidemia, hypertriglycemia, hyperglycemia, and hyperlipoproteinenamia.
[0025] The term “cytochrome P450 enzyme” as used herein refers to the family of enzymes comprised of the cytochrome P450 system often called cyotchrome P's. It has become increasingly clear that inhibition of an enzyme or enzymes from this family is associated with deleterious effects which could be life threatening. For example, inhibition of the enzyme Cyp2D6, a member of the cytochrome P450 family, may cause serious drug-drug interactions and/or overdoses particularly in cases where patients are taking multiple medications. Thus, the present invention also relates to the use of a compound of formula I for the treatment or prevention of obesity and Related Diseases while minimizing undesirable drug-drug interactions in a patient who is also under medication with other drug(s) comprising administering a therapeutically effective amount of a compound of formula I to said patient.
[0026] The compound of the invention as illustrated in formula I occurs as the trans stereochemical isomer by virtue of the substituents at the 3- and 4-positions. More specifically, the group CH 3 , at the 3-position is situated in a trans configuration relative to the CH 3 group at the 4-position. As such, the compound can exist as the trans (+) isomer of the formula
or the trans (−) isomer of the formula
[0027] The present invention comtemplates the individual trans (+) and (−) stereoisomers, as well as the mixture of the trans stereoisomers.
[0028] Also, for the group —CH 2 CH 2 C(OH)cyclohexyl there is the possibility of a chiral center, i.e. the carbon atom attached to the OH group is asymmetric. Therefore, the compound can further exist as the individual R or S stereoisomers, or the mixture of the isomers, and all are contemplated within the scope of the compounds of the present invention. A most preferred compound of the invention is trans(+)-1-[-3S-(3-hydroxy-3-cyclohexylpropyl)]-3(R),4(R)-dimethyl-4-(3-phenylcarboxamido) piperidine.
[0029] The compound of formula I forms pharmaceutically acceptable acid addition salts with a wide variety of inorganic and organic acids. The compound of formula I preferably exists as a pharmaceutically acceptable salt. More preferred is the hydrochloride, or the bisulfate salt of the compound of formula I.
[0030] In another embodiment, the compound(s) of the present invention has shown antiorexigenic effects, and is thus useful as an appetite suppressant. Reduction of food intake over a period of time has been observed with rats fed a diet containing a compound of the invention. Interestingly the reduction in food intake was found to be more significant at each point in time for the compound of the present invention than with the clinical trial compound disclosed in U.S. Pat. No. 4,891,379.
Preparing the Compound of the Invention
[0031] The compound of the present invention may be prepared by a variety of procedures known to one of skill in the art. The preferred procedure involves transforming the OH group at the 3-position of the phenyl group of 3-,4-dimethyl-4-(3-hydroxyphenyl)piperidine into a good leaving group for example, by triflate formation or mesylate formation followed by a subsequent nucleophilic attack by a carbonyl group or synthon thereof. The carbonyl group or synthon thereof is then converted to the amide compound of formula I. The starting material 3,4-dimethyl-4-(3-substituted phenyl)piperidine (1) is reacted with an appropriate acylating agent (2) to provide the corresponding intermediate (3) which is reduced to the intermediate (4) and then converted to the compound of the present invention (6) via a triflate intermediate (5) under standard conditions as shown in Scheme 1.
[0032] The first step of the above-described process wherein X is hydroxy, necessitates the use of coupling reagents commonly employed in the synthesis of peptides. Examples of such coupling reagents include the carbodiimides such as N,N′-dicyclohexylcarbodiimide, N,N′-diisopropylcarbodiimide, or N,N′-diethylcarbodiimide; the imidazoles such as carbonyldiimidazole; as well as reagents such as N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). The direct coupling of a substituted carboxylic acid and a 3-substituted-4-methyl-4-(3-substitutedphenyl)piperidine (1) is carried out by adding about an equimolar quantity of the piperidine starting material to a solution of the carboxylic acid in the presence of an equimolar quantity or slight excess of coupling reagent. The reaction generally is carried out in an unreactive organic solvent such as dichloromethane or N,N-dimethylformamide, and usually is complete within about twenty-four hours when conducted at a temperature of about 0° C. to about 30° C. The product is then typically isolated by filtration. The acylated product (3) thus formed may be further purified, if needed, by any of several routine methods, including crystallization from common solvents, chromatography over solid supports such as silica or alumina, and related purification techniques.
[0033] The reaction (as in Scheme 1) wherein X is other than hydroxy is conducted as follows. The preferred leaving group in this reaction is where X is halogen, especially chloro. The reaction can be carried out by combining the substituted carboxylic acid derivative with about an equimolar quantity of the 3-substituted-4-methyl-4-(3-substituted phenyl)piperidine in a solvent such tetrahydrofuran, diethyl ether, dichloromethane, dioxane, dimethylsulfoxide, N,N-dimethylformamide, benzene, toluene, and the like. If desired, a base can be utilized in the acylation reaction when X is halogen to act as an acid scavenger. Commonly used bases include sodium carbonate, potassium carbonate, pyridine, triethylamine and related bases. Bases such as pyridine act as their own solvent and need no additional solvent. The reaction generally is substantially complete after about two to about 200 hours when carried out at a temperature of about 20° C. to about 200° C., preferably from about 30° C. to about 100° C. The product of the reaction may be isolated by simply removing the reaction solvent, for instance by evaporation under reduced pressure. Also, the reaction mixture may be added to water, and the product collected by filtration or extracted into a water immiscible solvent. The compound (3) thus isolated can be further purified, if desired, by any of several well-known techniques. A suitable R 1 group for the above reaction is methyl, ethyl or the like.
[0034] The acylated intermediate (3) prepared as above is reduced according to standard procedures to provide the intermediate (4) useful in preparing the present compounds. Typical reducing agents suitable for use include the hydride reducing agents such as lithium aluminum hydride and sodium bis(2-methoxyethoxy)aluminum hydride, which is preferred. Typically, an excess of reducing agent is combined with the acylated intermediate in a mutual solvent. The reaction is substantially complete after about one to about 12 hours when conducted at a temperature in the range of about 20° C. to about 100° C. The desired intermediate (4) may then be isolated by procedures well known to those of ordinary skill in the art.
[0035] The intermediate (4) may also be prepared by the direct substitution of a halogen substituted compound with the 3,4-dimethyl-4-(3-substituted phenyl)piperidine intermediate. This reaction is represented by the following scheme (2) wherein R 1 is hydrogen, C 1 -C 4 alkyl, or benzyl; R 3 is cyclohexyl; Z is —CH(OH)—; and Y is halogen.
The above reaction (scheme 2) is conducted by combining approximately equimolar amounts of the two starting materials (compounds 1 and 2b) (salts, stereoisomers, and racemates thereof) in a mutual solvent. A slight excess of the halogen-substituted compound (2b) may be employed to ensure complete reaction. Typical mutual solvents suitable for use in this reaction include aprotic solvents such as N,N-dimethylformamide and the like. Further, the reaction is preferably conducted in the presence of a base, such as sodium bicarbonate, which acts as an acid scavenger for the hydrohalic acid, which is formed as a by-product of the reaction. The reaction is generally complete after about 30 minutes to 24 hours when conducted at a temperature in the range of about 40° C. to about 100° C. The product is isolated and purified, if needed, by standard procedures or isolation procedures described herein.
[0036] Other methods of preparing the intermediates (3) and/or (4) or analogs thereof, are disclosed in U.S. Pat. Nos. 4,081,450, and 4,191,771, European Patent application EP.1 072 592 A2 and references disclosed therein.
[0037] The intermediate (4) however prepared, is activated at the hydroxy group by reaction with a methane sulfonic anhydride, triflic anhydride, or other reagents known to one of skill in the art to convert the hydroxyl group to a good leaving group forming an isolatable intermediate triflate or mesylate. The intermediate triflate for example, is converted to the compound (5) by nucleophilic attack of a carbonyl group or synthon thereof followed by esterification. In a preferred mode of reaction, the carbonyl group is inserted by use of palladium reagents (carbonyl insertion reaction) often accompanied by in-situ esterification to afford the ester (5)(wherein R a is C 1 -C 4 alkyl or benzyl). The ester (5) is converted to the amide (6) by sealed tube ammonolysis conditions or other reaction conditions known to one of skill in the art. An alternate route involving direct conversion of a triflate intermediate to a carboxamide is illustrated in Wentland, et al., Biorganic and Medicinal Chemistry Letters 11 (2001) 623-626 and also in Wentland, et al., Biorganic and Medicinal Chemistry Letters 11 (2001) 1717-1721. For the compound of the present invention, the route involving converting the triflate to an isolable ester intermediate was found to be most workable and therefore preferred. Additional information for preparing the compound of formula I is available in the experimental section.
[0038] Salts of piperidines are prepared by methods commonly employed for the preparation of amine salts. In particular, acid addition salts of the piperidines are prepared by reaction of the piperidine with an appropriate acid of pKa less than about 4, generally in an unreactive organic solvent. Suitable acids include mineral acids such as hydrochloric, hydrobromic, hydriodic, sulfuric, phosphoric, and like acids. Organic acids are also used, for example acetic acid, p-toluenesulfonic acid, chloroacetic acid, and the like. The usual solvents used in the reaction include acetone, tetrahydrofuran, diethyl ether, ethyl acetate, and the like. Quaternary salts can be prepared in generally the same way by reaction of the piperidne with an alkylsulfate or alkyl halide, for example, methyl sulfate, methyl iodide, ethyl bromide, propyl iodide, and the like.
[0039] The 3,4-dimethyl-4-(3-hydroxy- or -alkanoyloxyphenyl)piperidine derivative (1) employed as starting material in the synthesis of the compound of the present invention is prepared by the general procedures taught by Zimmerman in U.S. Pat. Nos. 4,081,450, and 4,191,771 and references therein, and procedures disclosed in European Patent Application No. 1 072 592 A2 and known and applicable modifications thereof. The above references for the preparation of the starting material 3,4-dimethyl-4-(3-hydroxy- or -alkanoyloxyphenyl)piperidine derivative (1), are incorporated by reference in their entirety where applicable.
[0040] As noted above, the compounds of the present invention may exist as the resolved stereoisomers. The preferred procedure employed to prepare the resolved starting materials used in the synthesis of these compounds includes treating a 1,3-dialkyl-4-methyl-4-(3-alkoxyphenyl)piperidine with either (+)- or (−)-dibenzoyl tartaric acid to provide the resolved intermediate. This compound is dealkylated at the 1-position with vinyl chloroformate and finally converted to the desired 4-(3-hydroxyphenyl)piperidine isomer.
[0041] As will be understood by one skilled in the art, the individual trans stereoisomers of the compound of the present invention may also be isolated with either (+)- or (−)-dibenzoyl tartaric, or other resolving agents and/or techniques known to one of skill in the art, from the corresponding racemic mixture of the compound of the invention.
EXPERIMENTAL
[0042] The following Example illustrates a method for the preparation of the compound of the present invention.
EXAMPLE
Synthesis of 3-[1-(3-Cyclohexyl-3-hydroxy-propyl)-3,4-dimethyl-piperidin-4-yl]-benzamide
Synthesis of Trifluoro-methanesulfonic acid 3-[1-(3-cyclohexyl-3-hydroxy-propyl)-3,4-dimethyl-piperidin-4-yl]-phenyl ester
[0043]
A 250 mL round bottom flask equipped with an addition funnel and nitrogen inlet was charged with 2 g (5.8 mmol) of trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidine prepared following the procedure disclosed in U.S. Pat. No. 4,191,771. The flask was then charged with 3.2 mL (23.0 mmol) of triethylamine, and 35 mL of dichloromethane. While stirring at room temperature, 2.3 g (6.4 mmol) of N-phenyltrifluoromethanesulfonimide in 5 mL of dichloromethane was added to the reaction dropwise via an addition funnel. The reaction mixture was stirred at room temperature for four hours. The reaction mixture was concentrated on a rotary evaporator to yield 4.3 g of crude product. The crude product was purified by flash chromatography on silica gel eluting with 1% conc. ammonium hydroxide/10% ethanol in chloroform to yield 2.0 g (4.2 mmol) of trifluoro-methanesulfonic acid 3-[1-(3-cyclohexyl-3-hydroxy-propyl)-3,4-dimethyl-piperidin-4-yl]-phenyl ester. Electrospray MS M+1 ion=478.6, H 1 NMR.
Synthesis of 3-[1-(3-Cyclohexyl-3-hydroxy-propyl)-3,4-dimethyl-piperidin-4-yl]-benzoic acid methyl ester
[0044]
A 100 mL sealed tube was charged with 2 g (4.2 mmol) of trifluoro-methanesulfonic acid 3-[1-(3-cyclohexyl-3-hydroxy-propyl)-3,4-dimethyl-piperidin-4-yl]-phenyl ester, 94 mg (0.42 mmol) of palladium acetate, 465 mg (0.84 mmol) of dppf, 1.29 mL (9.2 mmol) of triethylamine, 20 mL of methanol, and 32 mL of dimethylsulfoxide (DMSO). Carbon monoxide was bubbled subsurface into the reaction for about ten minutes. The tube was sealed and heated at 65° C. for four hours. The reaction mixture was concentrated on a rotary evaporator to a residue. Water (approximately 100 mL) was added to the residue followed by extraction of the organic phase with ethyl acetate (3×100 mL). The organic extracts were dried over sodium chloride/sodium sulfate, filtered, and then concentrated to yield 2.4 g of crude product. The crude product was purified by flash chromatography on silica gel eluting with 1% conc. ammo nium hydroxide/10% ethanol in chloroform to yield 0.7 g (1.8 mmol) of 3-[1-(3-cyclohexyl-3-hydroxy-propyl)-3,4-dimethyl-piperidin-4-yl]-benzoic acid methyl ester. HPLC-MS=100% M+1 ion 388.23.
Synthesis of 3-[1-(3-Cyclohexyl-3-hydroxy-propyl)-3,4-dimethyl-piperidin-4-yl]-benzamide
[0045]
[0046] A reaction tube was charged with 0.7 g (1.8 mmol) of 3-[1-(3-cyclohexyl-3-hydroxy-propyl)-3,4-dimethyl-piperidin-4-yl]-benzoic acid methyl ester, 5 mg of sodium cyanide, and 30 mL of methanol. Ammonia was bubbled subsurface into the reaction for ten minutes then the tube was sealed at heated at 85° C. for sixteen hours. The reaction was driven to completion or substantial completion by daily addition of sodium cyanide and ammonia over a period of seven days or until the reaction was satisfactorily complete by HPLC analysis. Care is taken to cool the tube to between 0° C. and room temperature before addition of each new batch of sodium cyanide and ammonia. The reaction mixture is concentrated on a rotary evaporator to yield 0.6 g of crude product. The crude product is purified by flash column chromatography on silica gel eluting with 1% conc. ammonium hydroxide/10% ethanol in chloroform to yield 260 mg (0.7 mmol) of 3-[1-(3-Cyclohexyl-3-hydroxy-propyl)-3,4-dimethyl-piperidin-4-yl]-benzamide. HPLC=98%, Electrospray MS M+1 ion=373.1, H 1 NMR.
Method of Using the Invention
[0047] As noted above, the compound of the present invention is useful in blocking the effect of agonists at mu, kappa, and/or delta receptors. As such, the present invention also provides a method for blocking a mu, kappa, delta or receptor combination (heterodimer) thereof in mammals comprising administering to a mammal requiring blocking of a mu, kappa, delta or combinations of mu, kappa, and/or delta receptors, a receptor blocking dose of a compound of formula I.
[0048] The term “receptor blocking dose”, as used herein, means an amount of compound necessary to block a mu, kappa, or delta or receptor combination (heterodimer) thereof receptor following administration to a mammal requiring blocking of a mu, kappa, or delta or receptor combination (heterodimer) thereof receptor. The active compounds are effective over a wide dosage range. For example, dosages per day will normally fall within the range of about 0.05 to about 250 mg/kg of body weight. In the treatment of adult humans, the range of about 0.5 to about 100 mg/kg, in single or divided doses, is preferred. However, it will be understood that the amount of the compound actually administered will be determined by a physician in light of the relevant circumstances, including the condition to be treated, the choice of compound to be administered, the age, weight, and response of the individual patient, the severity of the patient's symptoms, and the chosen route of administration, and therefore the above dosage ranges are not intended to limit the scope of the invention in any way. The compounds may be administered by a variety of routes such as the oral, transdermal, subcutaneous, intranasal, intramuscular and intravenous routes.
[0049] A variety of physiologic functions have been shown to be subject to influence by mu, kappa, or delta or receptor combination (heterodimers) thereof in the brain. As such, the compound of the present invention is believed to have the ability to treat a variety of disorders in mammals associated with these receptors such as eating disorders, opioid overdose, depression, smoking, alcoholism, sexual dysfunction, shock, stroke, spinal damage and head trauma. As such, the present invention also provides methods of treating the above disorders at rates set forth above for blocking the effect of agonists at a mu, kappa, delta or receptor combination (heterodimer) thereof. The compound of the present invention has been found to display excellent activity in an opioid receptor binding assay which measures the ability of the compounds to block the mu, kappa, delta or receptor combination (heterodimer) thereof.
[0050] Futhermore, the compound of the present invention has been found to exhibit an unexpected and significant increase in efficacy compared to compounds disclosed in published European Patent application number 1 072592A2 (i.e. compound of example 2). The compound of the present invention is also unique because in addition to increased or comparable efficacy over disclosed compounds, it also provides significantly improved bioavailability characteristics. The increased efficacy and the superior bioavailability characteristics of the present compound were neither appreciated nor suggested by the prior art. Thus the compound of the present invention is believed to provide truly superior and unexpected advantages over the prior art (see Table (1) infra).
[0051] The assay for biological activity i.e. binding affinity was conducted using the following procedure.
[0000] GTPγS Binding Assay
[0052] An SPA-based GTPgS assay format was developed based on previous opioid (Emmerson et al., J. Pharm Exp Ther 278,1121,1996; Homg et al., Society for Neuroscience Abstracts, 434.6, 2000) and muscarinic (DeLapp et al., JPET 289, 946, 1999) assay formats. Membranes were resuspended in 20 mM HEPES, 100 mM NaCl, 5 mM MgCl2, 1 mM DTT, and 1 mM EDTA. Fifty mL of GTPγ[35S], compound, membrane suspension (20 microgram/well), and wheat germ agglutinin coated SPA beads (1 mg/well) were added to clear bottom 96 well assay plates. GDP (200 mM) was added to the membrane solution prior to addition to the assay plates. Plates were sealed and incubated for four hours at room temperature then placed in a refrigerator overnight to allow the beads to settle. Signal stability at 4° C. was determined to be >60 hours. Plates were warmed to room temperature and counted in a Wallac Microbeta scintillation counter. For antagonist assays, specific agonists were added at the following concentrations: (MOR) DAMGO 1 micromolar, (DOR) DPDPE 30 nM, (KOR) U69593 300 nM. Kb's were determined by Cheng-Prusoff equation (Cheng and Prusoff, 22,3099 1973).
[0053] Table 1 provides a summary of in vitro activity in a GTP-γ-S functional antagonist assay. This data shows that the compound of formula I is at least 2 fold more potent than the compound of formula (II) (the closest compound exemplified in European Patent application No. 1072592 A2), and comparable potency compared to compound (III), a previous clinical trial candidate discontinued for unacceptable bioavailability which is disclosed and claimed in U.S. Pat. No. 4,891,379.
TABLE 1 In Vitro GTPγ-S human opioid receptors expressed in Mu Kappa Delta Compound nM nM nM (I) 0.12 1.93 2.81 (II) 0.31 4.51 8.72 (III) 0.04 0.32 1.19
[0054] Table 2 provides data showing that the compound of formula (I) also shows better bioavailability than the compound of formula (III), a previous clinical trial candidate disclosed and claimed in U.S. Pat. No. 4,891,379.
TABLE 2 Meta- bolis Rat (I) 32 (II) 2.5
[0055] The compound of formula I, in addition to increased efficacy and bio-availability compared to previously disclosed compounds, also exhibits a significantly reduced potential for inhibiting the cytochrome P450 enzyme system, a surprising and unexpected finding that spells improved safety and reduced potential for drug-drug interactions etc. The reduced potential for inhibition of cytochrome P450 was discovered using a standard assay that monitors the compound's ability to inhibit Cyp2D6 a member of the cytochrome P450 family of enzymes. The protocol and comparative results are provided below.
[0000] Assay for Inhibition of CYP2D6 Activity
[0056] The inhibition of human Cytochrome 2D6 (CYP2D6) activity was studied using a validated high through-put screening assay. A 3 uL aliquot of an 8 mM stock solution of compound was delivered to 397 uL of pH 7.4 (50 mM) phosphate buffer resulting in an initial concentration of 60 uM. The compound dose solutions were prepared by serial dilutions to produce concentrations of 60, 19.4, 6.28, 2.03,0.66, 0.21, 0.069, and 1 uM. A 6 mM NaDPH stock solution was prepared by addition of 100 mg of NaDPH to 20 mL of pH 7.4 buffer. A 600 uL aliquot of Human liver Microsomes (HLM-20.0 mg/ml) was added to 20 ml of pH 7.4 phosphate buffer to produce a 0.6 mg/ml solution of HLM. To the HLM mixture was added 120 uL of a 10 mM bufurolol solution (CYP2D6 substrate) producing a final bufuralol concentration of 60 uM. To each assay plate was added 100 uL of the compound dose solutions, 25 uL NaDPH and 25 uL HLM/bufurolol solution. Samples were incubated at 37° C. for 10 minutes and the reaction was quenched with 25 uL of a 2% perchloric acid solution, followed by centrifugation at 3200 rpm for 30 min. The resulting supernatant was assayed for bufurolol concentrations using a Turbo Ion Spray API 150EX MS method. The calculated IC50 value represents the compound concentration that results in a 50% reduction in burfurolol consumption. Table 3 below provides a comparative data for inhibition of CyP2D6.
TABLE 3 Compound # Cyp2D6 IC 50 1 38.96 II 2.46 III 9.27
[0057] Table 3 shows that the compound of formula I is nearly 16 times less likely to cause inhibition of the cytochrome P450 enzyme compared to the prior clinical trial candidate compound (II) claimed in U.S. Pat. No. 4,891,379. Furthermore, the data shows that the compound of formula (I) is over 4 times less likely to inhibit the cytochrome P450 enzyme system compared to the compound of formula (III) which is disclosed as example 2 in European Patent application number 1072592 A2 published Jan. 31, 2001.
[0000] Antiorexigenic Effect
[0058] Compounds were tested for effects on food consumption in male Long-Evans rats which had been fasted for 18 hours prior to testing. The weight of food consumed was measured for groups of 6 rats treated with test substance and compared to the food consumed by an untreated control group of 6 animals. Oral administration of a 3 mg/kg dose of a compound of formula I resulted in a statistically significant inhibition of cumulative food consumed, as measured over 1 hour, 2 hour and 4 hour time periods. Oral administration of a 3 mg/kg dose of the previous clinical trial compound (II) disclosed in U.S. Pat. No. 4,891,379 did not produce statistically significant inhibition of food consumption over the same time periods.
Formulation
[0059] While it is possible to administer a compound of the invention directly without any formulation, the compounds are preferably employed in the form of a pharmaceutical formulation comprising a pharmaceutically acceptable carrier, diluent or excipient and a compound of the invention. Such compositions will contain from about 0.1 percent by weight to about 90.0 percent by weight of a present compound. As such, the present invention also provides pharmaceutical formulations comprising a compound of the invention and a pharmaceutically acceptable carrier, diluent or excipient therefor.
[0060] In making the compositions of the present invention, the active ingredient will usually be mixed with a carrier, or diluted by a carrier, or enclosed within a carrier which may be in the form of a capsule, sachet, paper or other container. When the carrier serves as a diluent, it may be a solid, semi-solid or liquid material that acts as a vehicle, excipient or medium for the active ingredient. Thus, the composition can be in the form of tablets, pills, powders, lozenges, sachets, cachets, elixirs, emulsions, solutions, syrups, suspensions, aerosols (as a solid or in a liquid medium, and soft and hard gelatin capsules.
[0061] Examples of suitable carriers, excipients, and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, starches, gum acacia, calcium phosphate, alginates, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, tragacanth, gelatin, syrup, methyl cellulose, methyl- and propylhydroxybenzoates, talc, magnesium stearate, water, and mineral oil. The formulations may also include wetting agents, emulsifying and suspending agents, preserving agents, sweetening agents or flavoring agents. The formulations of the invention may be formulated so as to provide quick, sustained, or delayed release of the active ingredient after administration to the patient by employing procedures well known in the art.
[0062] For oral administration, a compound of this invention ideally can be admixed with carriers and diluents and molded into tablets or enclosed in gelatin capsules.
[0063] The compositions are preferably formulated in a unit dosage form, each dosage containing from about 1 to about 500 mg, more usually about 5 to about 300 mg, of the active ingredient. The term “unit dosage form” refers to physically discrete units suitable as unitary dosages for human subjects and other mammals, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect, in association with a suitable pharmaceutical carrier.
[0064] In order to more fully illustrate the operation of this invention, the following formulation examples are provided. The examples are illustrative only, and are not intended to limit the scope of the invention. The formulations may employ as active compounds any of the compounds of the present invention.
[0000] Formulation 1
[0065] Hard gelatin capsules are prepared using the following ingredients:
Amount per Concentration Compound capsule (mg) by weight (%) Cyclohexyl-3-hydroxy- 250 55 propyl)-3,4-dimethyl- piperidin-4-yl]-benzamide Starch dried 200 43 Magnesium stearate 10 2
The above ingredients are mixed and filled into hard gelatin capsules in 460 mg quantities.
Formulation 2
[0066] Capsules each containing 20 mg of medicament are made as follows:
Amount per Concentration Compound capsule (mg) by weight (%) Cyclohexyl-3-hydroxy- 20 10 propyl)-3,4-dimethyl- piperidin-4-yl]-benzamide Starch 89 44.5 Microcrystalline 89 44.5 cellulose Magnesium stearate 2 1
The active ingredient, cellulose, starch and magnesium stearate are blended, passed through a No. 45 mesh U.S. sieve and filled into a hard gelatin capsule.
Formulation 3
[0067] Capsules each containing 100 mg of active ingredient are made as follows:
Amount per Concentration Compound capsule (mg) by weight (%) Cyclohexyl-3-hydroxy- 100 30 propyl)-3,4-dimethyl- piperidin-4-yl]-benzamide Polyoxyethylene 50 mcg 0.02 Sorbitan monooleate Starch powder 250 69.98
The above ingredients are thoroughly mixed and placed in an empty gelatin capsule.
Formulation 4
[0068] Tablets each containing 10 mg of active ingredient are prepared as follows:
Amount per Concentration Compound capsule (mg) by weight (%) Cyclohexyl-3-hydroxy- 10 10 propyl)-3,4-dimethyl- piperidin-4-yl]-benzamide Starch 45 45 Microcrystalline 35 35 cellulose Polyvinylpyrrolidone 4 4 (as 10% solution in water) Sodium carboxymethyl 4.5 4.5 starch Magnesium stearate 0.5 0.5 talc 1 1
The active ingredient, starch and cellulose are passed through a No. 45 mesh U.S. sieve and mixed thoroughly. The solution of polyvinylpyrrolidone is mixed with the resultant powders which are then passed through a No. 14 mesh U.S. sieve. The granule so produced is dried at 50-60° C. and passed through a No. 18 mesh U.S. sieve. The sodium carboxymethyl starch, magnesium stearate and talc, previously passed through a No. 60 mesh U.S. sieve, are then added to the granule which, after mixing, is compressed on a tablet machine to yield a tablet weighing 100 mg.
Formulation 5
[0069] A tablet formula may be prepared using the ingredients below:
Amount per Concentration Compound capsule (mg) by weight (%) Cyclohexyl-3-hydroxy- 250 38 propyl)-3,4-dimethyl- piperidin-4-yl]-benzamide Cellulose 400 60 microcrystalline Silicon dioxide fumed 10 1.5 Stearic acid 5 0.5
The components are blended and compressed to form tablets each weighing 665 mg.
Formulation 6
[0070] Suspensions each containing 5 mg of medicament per 5 ml dose are made as follows:
Amount per 5 mL Compound suspension (ml) Cyclohexyl-3-hydroxy- 5 propyl)-3,4-dimethyl- piperidin-4-yl]-benzamide Sodium carboxymethyl 50 cellulose Syrup 1.25 Benzole acid solution 0.10 Flavor q.v. Color q.v. Water q.s. to 5 mL
The medicament is passed through a No. 45 mesh U.S. sieve and mixed with the sodium carboxymethylcellulose and syrup to form a smooth paste. The benzoic acid solution, flavor and color is diluted with some of the water and added to the paste with stirring. Sufficient water is then added to produce the required volume.
Formulation 7
[0071] An aerosol solution is prepared containing the following components:
Concentration by weight Compound (percent) Cyclohexyl-3-hydroxy-propyl)-3,4- 0.25 dimethyl-piperidin-4-yl]-benzamide hydrochloride Ethanol 29.75 Propellant 22 70.0 (chlorodifluoromethane)
The active compound is mixed with ethanol and the mixture added to a portion of the Propellant 22, cooled to −30° C. and transferred to a filling device. The required amount is then fed to a stainless steel container and diluted further with the remaining amount of propellant. The valve units are then fitted to the container. | A compound of the formula (I): or a pharmaceutically acceptable salt, enantiomer, racemate, diastereomers or mixtures thereof, or a solvate thereof, formulations and methods of use thereof are disclosed. | 2 |
RELATED APPLICATIONS
This application claims priority to, and benefit of, U.S. Provisional Patent Application No. 61/848,437, filed Jan. 4, 2013, and U.S. Provisional Patent Application No. 61/702,856 filed Sep. 19, 2012, all of which are incorporated by reference herein for all purposes.
TECHNICAL FIELD
The invention relates generally to mechanical systems and, more particularly, the invention relates to a remote controlled personal robotic device.
DESCRIPTION OF THE RELATED ART
As computers have grown increasingly important in today's society, humans have created robotic devices to automate and enhance various activities that have traditionally been performed manually. Domesticated pets, livestock animals and wild animals maintained in a controlled environment rely in great measure on the care and attention of humans to remain mentally and physically healthy and alert. Items that are assistive in nature to help owners maintain the well being of their animals can provide some portion of such care and attention. Animal owners are often hampered in their attempts to properly care for their animals when the owner is required to be geographically distant from the place their animals are kept. In many cases, animal owners are required to contract with third-party providers to perform simple tasks related to feeding, watering and administering medications to animals when the animal owner is not physically present to do so. Indeed, each year, numerous animals die or are caused physical or emotional harm due to the lack of proper care by owners who are geographically removed from the animal or due to the inadvertent or purposeful oversight of third-party animal caregivers.
SUMMARY
A robotic system for remote care and maintenance of animals is presented. According to one embodiment of the present disclosure, the system includes a housing and a mobility portion coupled to the housing and operable to move the housing. The system further includes a wireless data communications system disposed with the housing and wirelessly communicatively coupled with an external data communications system and an electronic data processor disposed within the system and controlling the mobility portion. In addition, the system includes food, water and medicine storage portions disposed within the housing. Further, the system includes a removable tray coupled to the housing and disposed proximate to a lower portion of the housing, the tray having a food tray portion operable to receive food from the food storage portion, a water tray portion operable to receive water from the water storage portion and a medicine tray portion operable to receive medicine from the medicine storage portion and a docking portion fixedly coupled to the housing and disposed generally on a rear portion of the housing, and connectively coupled to the food, water and medicine storage portions. Also, the system includes an internal electronic fence transceiver in wireless communication with an external electronic fence transceiver, the internal electronic fence transceiver disposed generally within the housing and the external electronic fence transceiver disposed externally and remote from the housing, wherein the internal electronic fence transceiver activates the external electronic fence transceiver when the external electronic fence transceiver is at least a predetermined distance from the housing.
BRIEF DESCRIPTION OF THE DRAWINGS
A better understanding of the claimed subject matter can be obtained when the following detailed description of the disclosed embodiments is considered in conjunction with the following figures.
FIG. 1 is a diagram illustrating a front view of an animal care device 100 according to one embodiment of the present disclosure;
FIG. 2A is a side view of tray 118 according to one embodiment of device 100 according to one embodiment of the present disclosure;
FIG. 2B is a top view of tray 118 according to one embodiment of device 100 according to one embodiment of the present disclosure;
FIG. 3 is a rear view of device 100 according to one embodiment of the present disclosure;
FIG. 4 is a side view of device 100 according to one embodiment of the present disclosure; and
FIG. 5 is a block diagram of a docking station 500 for device 100 according to one embodiment of the present disclosure.
DESCRIPTION
Humans have been making use of animals for both productive purposes, such as food and labor, and as companions, such as domesticated dogs and cats, since the earliest days of recorded history. In order to make use of these animals, the animals are typically kept in controlled or semi-controlled environments, such as houses and fenced outdoor areas, in order to control the movements of the animals and to protect the animals from predators. As a result of placing the animals in such environments, the animal must rely upon human assistance and support in order to survive. For example, domestic dogs and cats rely upon their owners to provide food and water. In addition, humans often train the animals to behave in certain ways that require human assistance or support as the animals may be physically incapable of performing such actions directly. For example, a door may need to be opened for a dog to allow the dog to relieve itself outside and a cat litter box requires periodic cleaning by the owner. However, the time available to an owner to perform these activities may be limited or the owner may need to be in a physically distant location from the animal due to, for example, job responsibilities. A pet care robot may be used to perform various animal care tasks that normally are performed by humans. For example, a pet care robot may be capable of walking and playing with a domestic dog that lives in a residence, and providing food, water and medicine to the dog. In addition, the pet care robot may provide a video and audio link to allow the dog to see the dog's owner, even though the owner is physically distant from the dog.
FIG. 1 is a diagram illustrating a front view of an animal care device 100 according to one embodiment of the present disclosure. The animal care device 100 , in various embodiments, provides various capabilities useful for providing care to an animal. For example, the animal care device 100 may walk a dog, provide food, water and medicine, or provide a video display showing a real-time or prerecorded video or image of the dog's owner. The animal care device 100 comprises a main body 102 , an upper body 104 , a pair of front wheels 106 , a pair of rear wheels 108 , a wireless system 110 , a camera 112 , a playing device 114 , audio/video display 116 , a tray 118 , an arm 120 , a scent emitter 130 and a heat/cold emitter 132 .
Main body 102 comprises the main physical support structure for the animal care device 100 . In the disclosed embodiment, main body 102 is generally cylindrical in shape and provides mounting support for front wheels 106 , rear wheels 108 , tray 118 and display 116 . Enclosed within main body 102 may be various electronic, electro-mechanical and mechanical systems for operation of animal care device 100 as described in greater detail below. Main body 102 may be formed from any suitable material, such as steel, aluminum, plastic or other composites as desired. For example, an animal care device 100 for use with a horse may require use of stronger, heavier or more costly materials than one for use with domesticated house pets. Main body 102 may alternatively be of other suitable shapes. Front wheels 106 are coupled to main body 102 and may be used to move and/or steer animal care device 100 . Rear wheels 108 are coupled to main body 102 and may alternatively or in addition to front wheels 106 to move and/or steer animal care device 100 . The illustration of the pair of front wheels 106 and rear wheels 108 represent only a single embodiment of device 100 , alternatively, various other drive systems may be used in various suitable combinations for the use of device 100 . For example, a single rear wheel 108 may be used and rear and front wheels 108 and 106 may be combined or organized in some other suitable format, such as four wheels with a steering system similar to a passenger vehicle. Also, device 100 may be a tracked vehicle for operation outdoors or in hostile environments, such as snow. Device 100 may further comprise electronic data processing capabilities, such as using a central processing unit (CPU) coupled to memory (not shown), in order to store and execute computer programming instructions to control device 100 .
In one embodiment, upper body 104 comprises a generally dome shaped element removably or fixably coupled to main body 102 . More specifically, upper body 104 and main body 102 may be formed as a single physical element or may represent separate physical elements that are coupled together. For example, upper body 104 may be designed to be removed from main body 102 to allow access to the interior of main body 102 for maintenance purposes. Upper body 104 may also be of other suitable shapes in various embodiments. Upper body 104 provides support and mounting locations for wireless system 110 , camera 112 and toy 114 . Enclosed within upper body 104 may be electrical, electro-mechanical and/or mechanical elements in support of device 100 as described in greater detail below. For example, portions of wireless system 110 may be disposed within the interior of upper body 104 . Upper body 104 may further be operable to rotate around a vertical axis independently of main body 102 , for example, to allow camera 112 to be pointed in various directions without rotating main body 102 as well. In general, similar to main body 102 , upper body 104 may be of a suitable shape and be made of suitable materials for a particular embodiment of device 100 .
Wireless system 110 comprises one or more of a global positioning system (GPS) transmitter/receiver, a wireless audio and/or data communications transmitter/receiver, such as an IEEE 802.11a/b/g/n or cellular data connection, Bluetooth transmitter/receiver, and a wireless fence system and suitable associated hardware, such as an antenna.
Camera 112 comprises any suitable still and/or video camera for generating an image and communicating the image to the wireless system 110 .
Toy 114 comprises a ball at the end of cord that is operable to be ejected away from device 100 and retracted back to device 100 . For example, a rubber ball may be used that is thrown for a dog to chase so that an owner can play with their dog from a remote location. Alternatively, toy 114 may comprise an imitation mouse that may be used to entertain a cat. In general, toy 114 may comprise any suitable object that is tethered to device 100 and ejected away from, and returned to, device 100 for interaction with an animal.
Tray 118 comprises a tray that is detachable from and re-attachable to device 100 in order to serve food, water and/or medicines to an animal. In one embodiment, device 100 lowers itself so that the bottom of tray 118 is sitting upon the ground and then releases tray 118 . Device 100 would then raise itself back to a normal operating height and move away from tray 118 to allow an animal to eat and drink from the tray. Device 100 would later return to tray 118 , lower itself such that the bottom of main body 102 is generally in contact with the top of tray 118 , and reattach tray 118 to main body 102 . Tray 118 may alternatively be removably coupled to main body 102 in any suitable way. For example, tray 118 may slide into and out of a cavity in main body 102 , for example using a lip on tray 118 that engages with a track below main body 102 . Tray 118 is described in more detail in association with FIGS. 2 a and 2 b below.
Arm 120 comprises a movable arm operable to deliver a payload 122 to an animal. In one embodiment, payload 122 comprises a syringe for providing an injection to an animal and arm 120 is capable of articulation appropriate for providing an injection. For example, an animal may be diabetic and require an insulin injection. For another example, payload 122 may comprise an injectable or spray-based tick repellent.
Scent emitter 130 comprises a suitable system for emitting a predetermined scent. As many animals rely on scent, as opposed to visual or auditory cues, device 100 provides the caregiver the ability to provide one or more scents as appropriate for the animal under care. For example, in one embodiment, scent emitter 130 may simply comprise a cavity with a fan where an object, such as clothing worn by a caregiver, is placed to provide a familiar scent to an animal. Alternatively, scent emitter 130 may comprise more complex systems using chemicals or concentrated scents that may be sprayed or otherwise emitted from device 100 as desired by a caregiver. Scent emitter 130 may operate independently according to predetermined criteria, such as time of day, and/or may be under direct remote control by the caregiver.
According to one embodiment of the present invention, a heat/cold emitter 132 may be included with device 100 , such as on main body 102 . Heat/cold emitter comprises one or both of a heater and/or air conditioner operable to heat and/or cool an area around device 100 . For example, in harsh environments it may be necessary to provide environmental controls for an animal, such as a pregnant horse that lives outside during unexpected weather changes or a domestic pet in the event of a power failure at a house.
FIG. 2 a is a side view of tray 118 according to one embodiment of device 100 . FIG. 2 b is a top view of tray 118 according to one embodiment of device 100 . As shown in FIG. 2 a , in one embodiment, tray 118 may comprise a cutout in the rear portion to account for movement of rear wheels 108 . In one embodiment, tray 118 further comprises at least one post 212 engageable within main body 102 to hold and release tray 118 from main body 102 . For example, posts 212 may engage with a solenoid within main body 102 to couple tray 118 to main body 102 and retain tray 118 with device 100 . In this example, the solenoids may be activated to latch with posts 212 or may use friction to retain tray 118 , while the deactivation of the solenoids would allow tray 118 to be released from a lower portion of main body 102 . Alternatively, tray 118 may be releasably coupled to main body 102 using a magnetic retention and release system or other suitable electrical, electro-mechanical or mechanical systems. As shown in FIG. 2 b , tray 118 comprises a food portion 200 , a water portion 202 and a medicine portion 204 . Food portion 200 receives food from device 100 and contains the food for consumption by an animal. Water portion 202 receives water or other liquids from device 100 and contains the water for consumption by an animal. Medicine portion 204 receives medicine in solid or liquid form from device 100 and contains the medicine for consumption by an animal. For example, tray 118 may be a plastic tray with open-topped compartments acting as portions 200 , 202 and 204 .
In one embodiment, tray 118 may further comprise sensor 210 . Sensor 210 is operable to detect that one or more of portions 200 , 202 and/or 204 are in need of refilling and signaling to device 100 that tray 118 needs refilling.
FIG. 3 is a rear view of device 100 according to one embodiment of the present disclosure. FIG. 4 is a side view of device 100 according to one embodiment of the present disclosure. FIGS. 3 and 4 are described together for greater clarity. Device 100 further comprises a plurality of charging ports 300 , an electrical port 302 , a directional system 304 , a water bin 320 , a food bin 322 , a medicine bin 324 , a waste bin 326 , a cleaning nozzle 330 , a water suction nozzle 332 , a battery 340 and a motor 342 . Charging ports 300 comprise a food port 310 , a water port 312 , a medicine port 314 and a waste port 316 . Electrical port 302 comprises suitable electrical interfaces for recharging device 100 from a power source, such as an electrical grid tied receptacle, solar panels, wind power or other suitable electrical power sources.
Food port 310 comprises a receptacle operable to receive animal feed to refill device 100 with feed for dispensing to an animal on tray 118 . Food received from food port 310 is stored in food bin 320 . Food bin 320 comprises any suitable container for solid or liquid items, is disposed within main body 102 and is coupled to food port 310 via a suitable tube or pipe. In one embodiment, food bin 320 may be removed from main body 102 by opening upper body 104 . For example, food bin 320 may be removed for cleaning or manual refilling.
Water port 312 comprises a receptacle operable to receive water to refill device 100 for dispensing to an animal on tray 118 . Water received from water port 311 is stored in water bin 322 . Water bin 322 comprises any suitable container for liquid items, is disposed within main body 102 and is coupled to water port 312 via a suitable tube or pipe. In one embodiment, water bin 322 may be removed from main body 102 by opening upper body 104 .
Medicine port 314 comprises a receptacle operable to receive medicines to refill device 100 for dispensing to an animal on tray 118 . Medicine received from medicine port 314 is stored in medicine bin 324 . Medicine bin 324 comprises any suitable container for solid or liquid items, is disposed within main body 102 and is coupled to medicine port 314 via a suitable tube or pipe. In one embodiment, medicine bin 324 may be removed from main body 102 by opening upper body 104 . In another embodiment, medicine bin 324 may be coupled to or accessible by payload 122 to in order to refill a syringe, for example, via a tube through arm 120 .
In addition, one or more of bins 320 , 322 , 324 and/or 326 may be refrigerated or heated as needed. For example, medicine bin 324 may be required to be kept refrigerated to keep medicine from spoiling.
Waste bin 326 receives water and other debris from suction nozzle 332 for storage until the contents of waste bin 326 are removed from device 100 via waste port 316 . Waste port 316 is coupled to waste bin 326 via a suitable tube or pipe to allow extraction of the contents of waste bin 326 .
Cleaning nozzle 330 comprises a device operable to expel water at a suitable level of pressure to clean tray 118 . Cleaning nozzle 330 is coupled to water bin 322 via a suitable tube or pipe. For example, cleaning nozzle 330 may comprise a water-spraying device that sprays water under pressure onto tray 118 . In one embodiment, cleaning nozzle 330 is of a suitable size and located within main body 102 at a location such that cleaning nozzle 330 sprays water onto tray 118 . In another example, cleaning nozzle 330 may be operable to move within main body 102 in order to clean portions of tray 118 . In addition, cleaning nozzle 330 may represent multiple cleaning elements, such as multiple sprayers, for cleaning tray 118 in various embodiments. For example, nozzle 330 may comprise or include a heated air emitter to dry tray 118 or other surfaces. Further, in one embodiment, a bin for a cleaning solution may be further coupled between water bin 322 and cleaning nozzle 330 . In yet another embodiment, nozzle 330 may be used to clean areas under device 100 after tray 118 has been detached, for example, to clean a floor.
Suction nozzle 332 comprises a device operable to remove water and/or debris from tray 118 and deposit the removed water and/or debris in waste bin 328 via a suitable tube or pipe. For example, as cleaning nozzle 330 is spraying water to clean tray 118 , suction nozzle 332 is removing the used water from tray 118 . In general, suction nozzle 332 comprises any suitable device or devices operable to remove used water and used cleaning fluids from tray 118 . In various embodiments, cleaning nozzle 330 and suction nozzle 332 may require the use of pumps (not shown) to generate suitable levels of water pressure for cleaning tray 118 and suction force to remove liquid and/or solid debris. For example, in one embodiment, suction nozzle 332 and cleaning nozzle 330 may be used to clean surfaces other than tray 118 , such as debris or waste on a floor or other surface. This embodiment may require the release of tray 118 prior to performing such cleaning activities.
Battery 340 comprises any suitable battery technology, such as lead-acid, NiMH, Lithium-Ion and NiCad, operable to power motor 342 and device 100 generally. Battery 340 is electrically coupled to charging port 300 and is recharged when charging port 300 is connected to an external power source. Battery 340 is sized as suitable for the animal being cared for by device 100 and the related power demands of motor 342 and the various electronics associated with device 100 , such as wireless communications system 110 . For example, an animal care device for taking care of horses in an outdoor field may be larger and require a stronger motor 342 and battery 340 to deal with the relatively harsh environment. In contrast, an animal care device that is primarily designed for use with a household pet may require a less powerful motor 342 and battery 340 .
Motor 342 comprises a suitable motor for driving front wheels 106 and/or rear wheels 108 , depending on the embodiment of device 100 , to allow device 100 to move from place to place. In one embodiment, motor 342 comprises an electric motor powered by battery 340 .
Directional system 304 comprises a movable joint operable to turn rear wheels 108 and to lower device 100 . In one embodiment, rear wheels 108 provide directional control for device 100 , while front wheels 106 provide the driving force to move device 100 . In addition, to order to release tray 118 on the ground, device 100 may lower itself so that the bottom of tray 118 is on or near the ground before releasing tray 118 . In this embodiment, directional system 304 pivots the rear wheels 108 to lower device 100 closer to the ground.
FIG. 5 is a block diagram of a docking station 500 for device 100 according to one embodiment of the present disclosure. Docking station 500 interfaces with charging ports 300 and electrical ports 302 . Docking station 500 comprises a food recharger port 510 , a water recharger port 512 , a medicine recharger port 514 , a waste removal port 516 and an electrical recharging interface 502 .
Food recharger port 510 comprises a suitable system to couple and decouple to food port 310 in order to refill food bin 322 via food port 310 . For example, food recharger port 510 and food port 310 may comprise a pair of generally hollow cylinders where one cylinder is slightly larger than the other cylinder to allow the smaller cylinder to enter into the larger cylinder to create a connection where solid and/or liquid food can pass through from food recharger port 510 to food port 310 into food bin 322 .
Water recharger port 512 comprises a suitable system to couple and decouple to water port 312 in order to refill water bin 320 . For example, water recharger port 512 and water port 312 may operate similarly to ports 510 and 310 .
Medicine recharger port 514 comprises a suitable system to couple and decouple to medicine port 314 in order to refill medicine bin 324 . For example, medicine recharger port 514 and medicine port 314 may operate similarly to ports 510 and 310 .
Waste removal port 516 comprises a suitable system to couple and decouple to waste port 316 in order to allow the emptying of waste bin 326 . For example, waste bin 326 may become partially or completely filled with solid and/or liquid waste as a result of the cleaning of tray 118 . Waste removal port 516 and waste port 316 may operate similarly to ports 510 and 310 .
Electrical recharging interface 502 comprises a suitable electrical system for recharging battery 340 via port 302 . For example, interface 502 and port 302 may comprise a suitable male/female electrical connection system.
As illustrated in FIG. 5 , docking station 500 may be located at a suitable location, such as a laundry room or outdoor location, for recharging and refilling device 100 . In one embodiment, docking station 500 is located outdoors and uses equipment suitable for outdoor and/or harsh environment use. Device 100 may automatically detect that one or more of bins 320 , 322 , 324 and 326 need refilling or emptying and return to docking station 500 and/or notify the caregiver that one or more of bins 320 , 322 , 324 and 326 need refilling, or that battery 340 needs recharging. Alternatively, the caregiver may remotely command device 100 to return to docking station 500 and/or device 100 may return to docking station 500 on a predetermined schedule or in response to other inputs. Docking station 500 itself may also be operable to generate a notification to the caregiver that the docking station 500 requires refilling.
In operation, device 100 may be used by an animal caregiver to assist with the care of one or more animals, regardless of whether the caregiver is physically located near the animals or is physically distant. Device 100 may be directly controlled by the caregiver, such as via a remote control or via a network connection, such as via an application on a computer, smartphone, tablet or other electronic computing device, that communicates with device 100 over a global computer network, such as the Internet. In addition, device 100 may be pre-programmed to perform various activities independently. For example, device 100 may provide food, water and/or medicine on tray 118 at predetermined times. Device 100 may also be controlled via a combination of independent programming and remote control.
Initially, or after one or more uses of device 100 , device 100 is filled and charged, or refilled and recharged, at docking station 500 . For example, device 100 may be controlled by a remote control by a human user or may be capable of automatically finding docking station 500 , such by GPS location or a beacon of a suitable type that device 100 may navigate to. In one embodiment, device 100 rolls to docking station 500 and reverses into docking station 500 . Rear wheels 108 then articulate to allow device 100 to lower or raise itself and couple ports 300 and 302 with docking station 500 .
The animal caregiver may interact with the animal using display 116 and camera 112 . Camera 112 allows the caregiver to see the animal, and may provide a pan, tilt and/or zoom functionality to improve viewing of the animal from a remote location, such as over the Internet. Display 116 allows the animal to see an image, such as the caregiver. Display 116 comprises any suitable display system for video and audio and is capable of receiving video and audio via wireless system 110 . The audio capabilities of display 116 allow the animal to both see and hear the caregiver, and allow the caregiver to hear the animal. For example, the caregiver could program device 100 to generate familiar sounds, such as a normal pre-sleep ritual, associated with the caregiver at a certain time, such as when the animal is sleeping. In general, device 100 may play pre-recorded audio and/or video messages at pre-determined times, in response to predetermined situations and/or as commanded remotely by the caregiver, such as via an application on a smartphone used by the caregiver. In addition, toy 114 allows the caregiver to play with the animal. For another example, a veterinarian may use camera 112 to evaluate the medical condition of an animal under the care of device 100 .
As device 100 is mobile, device 100 can move around with the animal. In one embodiment, wireless system 110 generates a signal usable as an electronic fence system. Electronic fences are commonly used to keep an animal, such as a dog, within a predefined area without the use of physical barriers. For example, the electronic fence may be linked to a shock collar that indicates that the dog is not allowed to go beyond a certain point. Such an electronic fence system, when incorporated into device 100 , allows device 100 to walk an animal. For example, an animal that has been trained that the animal can only go a certain distance, such as 50 feet, away from device 100 by the electronic fence, allows device 100 to walk the animal. More specifically, since the animal knows that it must remain within a certain distance from device 100 , or be subject to appropriate corrective measure, such as an audible signal or an electronic shock from a shock collar, device 100 could, for example, move down a sidewalk along a predetermined route, or under the remote control of a care giver, and walk an animal even though the care giver is not physically present. In one embodiment, the electronic fence collar worn by the animal contains a water immersion detection capability to detect if the animal has entered or fallen into a body of water, such as a swimming pool, lake or pond. In this embodiment, the collar may alert device 100 that the animal has entered a body of water and the device 100 may generate an alert, such as to the remote care giver or an emergency response group, or take other predetermined actions in response thereto.
Device 100 may use a GPS or other location device associated with device 100 and/or the animal being cared for to provide location information of the animal and/or device 100 to the animal caregiver. The location information may be used by device 100 to generate an alert to the caregiver and/or other people based on one or more predetermined conditions. For example, an alert could be generated if the animal goes beyond a certain distance from device 100 . In one embodiment, device 100 communicates with a device that tracks an animal's vital signs and responds appropriately in the event of a medical emergency. For example, if it is known that an animal has a medical condition that requires medicine only under certain circumstances, device 100 could provide such medicine via tray 118 or payload 122 when the medical condition is detected by the vital signs monitoring device, such as in response to low blood sugar, elevated blood pressure or elevated heart rate.
In addition, device 100 may include special programming to automatically handle emergency situations. For example, device 100 may be capable of communicating with a smoke and fire detection system in a house, and use the electronic fence functionality to bring a house pet outside in the event of a fire, such as by decreasing the distance of the electronic fence to keep the animal close to device 100 until device 100 and the animal have reached a safe or predetermined location. In one embodiment, device 100 may itself be equipped with a carbon monoxide detector, smoke detector, fire detector and/or other sensors to detect toxic fumes, smoke, fire or other hazards. For example, device 100 may include a glass break sensor along with programming to know that device 100 and an animal under the care of device 100 are alone in a structure, and that a glass break represents a potential intruder. For another example, device 100 may include programming to generate an alert to an emergency service, such as a fire department, that includes images, description and count of the animals under the care of device 100 . Such an alert may be sent when device 100 detects a hazardous situation, such as a fire, so that emergency responders are aware of the number and identity of animals in a structure. In addition, such an alert may include medical information, such as drug allergies, handicaps or pregnancy, of animals under care of device 100 to assist medical personnel in an emergency. Further, such an alert may also include the planned emergency evacuation location that device 100 will lead animals to in the event of an emergency to assist first responders in locating the animals. In general, device 100 may be programmed to communicate current and/or historical data associated with one or more sensors associated with device 100 to the caregiver and/or may be commanded by the caregiver to provide such data.
Tray 118 allows device 100 to feed, water and provide medicine to animal. In one embodiment, when an animal is to be fed, such as device 100 being preprogrammed with feeding times, determining feeding is necessary according to predetermined criteria or is commanded to feed the animal by the caregiver, device 100 fills tray 118 with food, water and medicine (if needed). For example, food, water and medicine from bins 320 , 322 and 324 may be respectively deposited in tray portions 200 , 202 and 204 . Tray 118 may use portions 200 , 202 and/or 204 for uses other than food, water and medicine. For example, portion 200 may be used as a cat litter box instead of providing food.
Device 100 then lowers itself so that the bottom of tray 118 is generally in contact with the ground and releases tray 118 . For example, device 100 may use rear wheels 108 to pivot the front of device 100 generally downward and then reverse, while allowing tray 118 to slide out. Alternatively, after the bottom of tray 118 is generally in contact with the ground, device 100 may release tray 118 and raise itself back up to a normal operating height and leave tray 118 on the ground. In general, any suitable system for releasing and recovering tray 118 may be used by device 100 .
After the animal has finished eating and drinking, device 100 retrieves and cleans tray 118 . For example, device 100 may lower itself over tray 118 , reattach tray 118 to device 100 , and raise itself back to a normal operating height. Alternatively, device 100 may slide tray 118 back into device 100 . Device 100 then cleans tray 118 using cleaning nozzle 330 and suction nozzle 332 . In one embodiment, device 100 may also use cleaning nozzle 330 and suction nozzle 332 to clean up detected debris, such as animal excrement or soil from a flowerpot knocked over by an animal. For example, caregiver could notice such debris via camera 112 and remotely control device 100 to leave tray 118 at a suitable location to allow use of nozzles 330 and 332 to clean up such debris. Alternatively or in addition, device 100 may automatically detect such debris and perform an appropriate cleaning operation. In addition, in one embodiment, device 100 may include a heater and/or air blower device associated with nozzles 330 and/or 332 , to dry the area cleaned by nozzles 330 and 332 . Further, in another alternative embodiment, scent emitter 130 may include the additional ability to emit a scent designed to be pleasing to humans, such as a scent similar an air freshener, that is emitted on or near a recently cleaned area to lessen offensive odors that may remain after the cleaning process.
Device 100 may also communicate with a home automation system that allows device 100 to open and close doors in a structure. For example, device 100 could wirelessly lock and unlock doors equipped with appropriate devices and push open doors for the animal at appropriate times, such as to allow the animal outside to play at certain times. In addition, device 100 may use such control over doors to control which areas of a structure that an animal is allowed to enter or prohibited from entering. Device 100 may also use such a home automation system to control environmental conditions, such as a heater or air conditioner. In addition, in one embodiment, device 100 may also communicate with a security system to allow an animal to move about the house without activating the alarm. For example, many security systems use motion detectors to provide security for a structure, however, such motion detectors often generate false alarms when an animal triggers the motion detector. Device 100 may avoid such false alarms by deactivating the motion detector when location information associated with an animal indicates that an animal is near a motion detector controlled area. For another example, device 100 may detect than a dog has spent a significant amount of time in front of a door that the dog uses when the dog needs to relieve itself. Upon detecting that the dog has been in front of the door for an appropriate period of time, device 100 could unlock and/or open the door to let the dog out, and deactivate the alarm system on that door to prevent a false alarm, while still allowing the alarm system to be used with an animal in the house.
Device 100 may also record the location of itself and/or the animal and provide such information to the caregiver. For example, device 100 may use the GPS device to provide a map of movements over a period of time to the caregiver via a remote data connection.
Device 100 may also include programming to detect if the animal has remained stationary for an abnormally long period of time, such as by using GPS information communicated from a collar worn by the animal to device 100 . For example, if a normally active animal has not moved for several hours, this may indicate a medical problem or that the animal is deceased. The programming may take any suitable action in response thereto, such as generating an alert to the caregiver or an emergency response group, or by providing medicine to the animal, such as via arm 120 .
As will be appreciated by one skilled in the art, aspects of the present invention may be embodied as a system, method or computer program product. Accordingly, aspects of the present invention may take the form of an entirely hardware embodiment, an entirely software embodiment (including firmware, resident software, micro-code, etc.) or an embodiment combining software and hardware aspects that may all generally be referred to herein as a “circuit,” “module” or “system.” Furthermore, aspects of the present invention may take the form of a computer program product embodied in one or more computer readable medium(s) having computer readable program code embodied thereon.
Any combination of one or more computer readable medium(s) may be utilized. The computer readable medium may be a computer readable signal medium or a computer readable storage medium. A computer readable storage medium may be, for example, but not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any suitable combination of the foregoing. More specific examples (a non-exhaustive list) of the computer readable storage medium would include the following: an electrical connection having one or more wires, a portable computer diskette, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or Flash memory), an optical fiber, a portable compact disc read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the foregoing. In the context of this document, a computer readable storage medium may be any tangible medium that can contain, or store a program for use by or in connection with an instruction execution system, apparatus, or device.
A computer readable signal medium may include a propagated data signal with computer readable program code embodied therein, for example, in baseband or as part of a carrier wave. Such a propagated signal may take any of a variety of forms, including, but not limited to, electro-magnetic, optical, or any suitable combination thereof. A computer readable signal medium may be any computer readable medium that is not a computer readable storage medium and that can communicate, propagate, or transport a program for use by or in connection with an instruction execution system, apparatus, or device.
Program code embodied on a computer readable medium may be transmitted using any appropriate medium, including but not limited to wireless, wireline, optical fiber cable, RF, etc., or any suitable combination of the foregoing.
Computer program code for carrying out operations for aspects of the present invention may be written in any combination of one or more programming languages, including an object oriented programming language such as Java, Smalltalk, C++ or the like and conventional procedural programming languages, such as the “C” programming language or similar programming languages. The program code may execute entirely on the user's computer, partly on the user's computer, as a stand-alone software package, partly on the user's computer and partly on a remote computer or entirely on the remote computer or server. In the latter scenario, the remote computer may be connected to the user's computer through any type of network, including a local area network (LAN) or a wide area network (WAN), or the connection may be made to an external computer (for example, through the Internet using an Internet Service Provider).
Aspects of the present invention may be described with reference to flowchart illustrations and/or block diagrams of methods, apparatus (systems) and computer program products according to embodiments of the invention. It will be understood that each block of the flowchart illustrations and/or block diagrams, and combinations of blocks in the flowchart illustrations and/or block diagrams, can be implemented by computer program instructions. These computer program instructions may be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions/acts specified in the flowchart and/or block diagram block or blocks.
These computer program instructions may also be stored in a computer readable medium that can direct a computer, other programmable data processing apparatus, or other devices to function in a particular manner, such that the instructions stored in the computer readable medium produce an article of manufacture including instructions which implement the function/act specified in the flowchart and/or block diagram block or blocks.
The computer program instructions may also be loaded onto a computer, other programmable data processing apparatus, or other devices to cause a series of operational actions to be performed on the computer, other programmable apparatus or other devices to produce a computer implemented process such that the instructions which execute on the computer or other programmable apparatus provide processes for implementing the functions/acts specified in the flowchart and/or block diagram block or blocks.
The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof.
The corresponding structures, materials, acts, and equivalents of all means or step plus function elements in the claims below are intended to include any structure, material, or act for performing the function in combination with other claimed elements as specifically claimed. The description of the present invention has been presented for purposes of illustration and description, but is not intended to be exhaustive or limited to the invention in the form disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the invention. The embodiment was chosen and described in order to best explain the principles of the invention and the practical application, and to enable others of ordinary skill in the art to understand the invention for various embodiments with various modifications as are suited to the particular use contemplated.
The flowchart and block diagrams in the Figures illustrate the architecture, functionality, and operation of possible implementations of systems, methods and computer program products according to various embodiments of the present invention. In this regard, each block in the flowchart or block diagrams may represent a module, segment, or portion of code, which comprises one or more executable instructions for implementing the specified logical function(s). It should also be noted that, in some alternative implementations, the functions noted in the block may occur out of the order noted in the figures. For example, two blocks shown in succession may, in fact, be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved. It will also be noted that each block of the block diagrams and/or flowchart illustration, and combinations of blocks in the block diagrams and/or flowchart illustration, can be implemented by special purpose hardware-based systems that perform the specified functions or acts, or combinations of special purpose hardware and computer instructions. | A system for remote animal care is presented. The system includes a housing and a mobility portion coupled to the housing and operable to move the housing. The system further includes a wireless data communications system. In addition, the system includes food, water and medicine storage portions disposed within the housing. Further, the system includes a removable tray coupled to the housing, the tray having a food tray portion, a water tray portion and a medicine tray portion. Also, a docking portion is coupled to the housing and connectively coupled to the food, water and medicine storage portions. Also, the system includes an internal electronic fence transceiver in wireless communication with an external electronic fence, wherein the internal electronic fence transceiver activates the external electronic fence transceiver when the external electronic fence transceiver is at least a predetermined distance from the housing. | 0 |
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates to a method and an apparatus for generating magnetic resonance images, and in particular to a method and an apparatus for generating magnetic resonance perfusion images.
[0003] 2. Description of the Prior Art
[0004] Magnetic resonance technology has been increasingly used in recent years to generate angiographic images since, relative to other medical imaging modalities such as, for example, radioscopy with x-rays or computed tomography, it has among other things, the advantage that patient and medical personal are subjected to no radiation exposure.
[0005] Magnetic resonance (MR) technology is a known technology with which images of the inside of an examination subject can be generated. For this purpose, the examination subject is positioned in a strong, static, homogeneous basic magnetic field (field strengths of 0.2 Tesla to 7 Tesla and higher) in an MR apparatus so that the subject's nuclear spins become oriented along the basic magnetic field. Radio-frequency excitation pulses are radiated into the examination subject to excite nuclear magnetic resonances, the excited nuclear magnetic resonances being measured (detected and MR images being reconstructed based thereon. For spatial coding of the measurement data, rapidly switched magnetic gradient fields are superimposed on the basic magnetic field. The acquired measurement data are digitized and stored as complex numerical values in a k-space matrix. An associated MR image can be reconstructed from the k-space matrix populated with such values by means of a multi-dimensional Fourier transformation.
[0006] Magnetic resonance can be used to produce images representing tissue perfusion, which is the flow of fluid in tissue. Perfusion studies allow an assessment to be made of the functioning of organs in vivo. For this purpose, in some techniques a contrast agent, which generates a signal that is detectable by magnetic resonance imaging, is injected into a subject, and the magnetic resonance data are acquired at a time when the contrast agent has optimally flowed into the region or anatomy of interest. Since the contrast agent is injected into the vascular system of the subject, the appearance of the contrast agent in the magnetic resonance image is representative of blood flow in the region or anatomy of interest. Magnetic resonance perfusion techniques are particularly useful in the context of magnetic resonance images of the head, in particular the brain, wherein cerebral blood flow (CBF) is identified. In another magnetic resonance perfusion technique using known arterial spin labeling (ASL) methods (which do not require injection of a contrast agent), images are often acquired with a perfusion-sensitive preparation (tag images) in alternation with non-perfusion-sensitive images (control images). The perfusion information in the tag images represents only a small change in the image contrast due to the inflowing tagged, i.e. magnetic resonance-labeled, spins into the region of interest, in the magnetic resonance images that are acquired. Typically, the perfusion signal is on the order of only a few percent of the total magnetic resonance image intensity.
[0007] Therefore, the extraction and quantification of relative perfusion images and quantitative perfusion images is prone to artifacts. Due to the low magnitude of the perfusion signal, multiple image acquisitions in the time frame of minutes are necessary. This results in a time series of images being acquired, with tag and control images alternating with each other. These tag and control images are combined with each other in pairs, by subtraction, so that multiple subtraction images are then available, which can be combined to form a resultant perfusion image. By combining multiple perfusion images, the low magnitude perfusion signal is made more readily visible in the combined image.
[0008] Due to the length of time that is necessary to acquire such an image series the most series source of image artifacts is patient movement, either gross (muscular) movement or natural movement such as respiration and cardiac motion. The control image is intended to be a static, snapshot image that can be ideally subtracted from the tag image that contains a small signal modulation originating from the perfusion. As noted above, this signal difference between the tag image and the control image is on the order of only a few percent. Artifacts can easily occur due to instabilities in the signal contribution to the control image, thereby causing the control image to deviate from a truly static image. In addition to non-static signal contributions originating within the examination subject, instabilities in the scanner that is used to acquire the magnetic resonance data may also cause the control image not to be truly static. An error as small as on the order of one percent in the control image can result in an artifact of approximately 100% false changes being attributed to the perfusion image.
[0009] As noted above, the typical processing that is employed to minimize this problem is to generate multiple perfusion images that are each a difference of a tag image and a control image. The multiple perfusion images are then averaged. A scaling or calibration factor can be applied to obtain a perfusion-weighted or a quantitative perfusion image. More advanced techniques use temporal interpolation methods of the time series of perfusion images, in order to recover the temporal resolution in the difference images. A typical procedure is to correct the original image series for motion before undertaking the averaging. This is accomplished by registering the image volumes of repeated measurements to a reference volume. This can significantly reduce the subtraction artifacts as long as the subsequent volumes can be fully registered. If motion artifacts occur within the volume, however, such volume-based registration fails, and leaves to significant subtraction artifacts, resulting in false perfusion images.
SUMMARY OF THE INVENTION
[0010] It is an object of the present invention to provide a method and apparatus for acquiring magnetic resonance perfusion images wherein the effect of motion artifacts is reduced, thereby improving the accuracy and quality of the resulting perfusion images.
[0011] The above object is achieved in accordance with the present invention in a method and apparatus for magnetic resonance perfusion imaging wherein the initially processed perfusion images, that respectively result from a processed combination, such as subtraction, of a tag image and a control image, are subjected to a quality control analysis before the initially processed images are combined to form the resultant perfusion image. In the quality control analysis, any initially processed image that fails to satisfy predetermined quality control criteria is rejected, and is not used in the subsequent averaging, or combining procedure, that is used to generate the combined perfusion image. Initially processed images that exhibit excessive motion artifacts therefore do not make a contribution to the combined perfusion image, so that the overall quality of the combined perfusion image is significantly improved.
[0012] The quality control can take place fully automatically in computerized fashion, or can be conducted with user interaction, so that a user can make his or her own judgment as to the level of quality of the images that will enter into the combining procedure to produce the combined perfusion image. Even if the procedure is implemented automatically, a user or operator still can be informed by an alarm or some other type of indicator if an excessive number of initially processed perfusion images of unacceptable quality are habitually occurring, so that the user or operator can take corrective steps in the settings of the magnetic resonance data acquisition system that is being employed for generating the magnetic resonance data.
[0013] In order to permit the user or the operator to undertake such appropriate corrective steps, the quality control analysis can be implemented in real time as the initially processed perfusion images are being acquired (generated). Alternatively, it is possible to generate the entire set of initially processed perfusion images and to then conduct the quality control analysis offline. In this embodiment, however, the final, combined perfusion images are not immediately available while the patient is still in the magnetic resonance data acquisition chamber.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] FIG. 1 schematically illustrates the basic components of a magnetic resonance imaging system constructed and operating in accordance with the present invention.
[0015] FIG. 2 schematically illustrates the method for obtaining a combined perfusion image in accordance with the present invention, embodying a quality control review of the initially processed perfusion images.
[0016] FIG. 3 is a flowchart illustrating an embodiment for implementing the quality control review in the method and apparatus according to the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0017] FIG. 1 schematically shows the design of a magnetic resonance apparatus 1 with its basic components. In order to examine a body by means of magnetic resonance imaging, various magnetic fields tuned to one another as precisely as possible in terms of their temporal and spatial characteristics are applied.
[0018] A strong magnet (typically a cryomagnet 5 with a tunnel-shaped opening) arranged in a radio-frequency shielded measurement chamber 3 generates a static, strong basic magnetic field 7 that typically amounts to 0.2 Tesla to 3 Tesla and more. A body or a body part (not shown here) to be examined is borne on a patient bed 9 and positioned in the homogeneous region of the basic magnetic field 7 .
[0019] The excitation of the nuclear spins of the body ensues via magnetic radio-frequency excitation pulses that are radiated via a radio-frequency antenna (shown here as a body coil 13 ). The radio-frequency excitation pulses are generated by a pulse generation unit 15 that is controlled by a pulse sequence control unit 17 . After an amplification by a radio-frequency amplifier 19 they are relayed to the radio-frequency antenna. The radio-frequency system shown here is merely schematically indicated. Typically more than one pulse generation unit 15 , more than one radio-frequency amplifier 19 and multiple radio-frequency antennas are used in a magnetic resonance apparatus 1 .
[0020] Furthermore, the magnetic resonance apparatus 1 has gradient coils 21 with which magnetic gradient fields for selective slice excitation and for spatial coding of the measurement signal are radiated in a measurement. The gradient coils 21 are controlled by a gradient coil control unit 23 that, like the pulse generation unit 15 , is connected with the pulse sequence control unit 27 .
[0021] The signals emitted by the excited nuclear spins are acquired by the body coil 13 and/or by local coils 25 , amplified by associated radio-frequency preamplifiers 27 and processed further and digitized by an acquisition unit 29 .
[0022] Given a coil (such as, for example, the body coil 13 ) that can be operated both in transmission mode and in acquisition mode, the correct signal relaying is regulated by an upstream transmission-reception diplexer 39 .
[0023] An image processing unit 31 generates from the measurement data an image that is presented to a user via an operator console 33 or is stored in a memory unit 35 . A central computer 37 controls the individual system components. The computer 37 is thereby fashioned such that the method according to the invention can be implemented by appropriate programming of the computer 37 .
[0024] The basic steps of the method in accordance with the present invention, that are implemented by appropriate programming of the computer 37 of the apparatus 1 shown in FIG. 1 , are illustrated in FIG. 2 . In the exemplary embodiment shown in FIG. 2 , for conducting a perfusion study with ASL, a series of alternating tag T and control C images are generated. Other ASL acquisition schemes are possible, and are also encompassed with the scope of the present method and apparatus. F or example, multiple tag images T can be acquired with only a single control image, or respective control images can be “shared” by more than one tag image (T 1 -C 1 , C 1 -T 2 , T 2 -C 2 , C 2 -T 3 , etc.). The basic concept of the present method and apparatus is to implement a quality control for any type of initially processed perfusion images.
[0025] In the exemplary embodiment of FIG. 2 , the tag images T and control images C, in pairs, are subtracted from each other. If necessary or desired, appropriate scaling and/or weighting can be implemented on the subtraction image. This results in a number of initially processed images. Other ways, besides simple subtraction, are also possible for producing the initially processed images and are encompassed within the scope of the present method and apparatus.
[0026] In accordance with the present invention, the initially processed images are subjected to an automatic or user-interactive quality control. In the example shown in FIG. 2 , the center initially processed image is determined not to satisfy the applicable quality control standard, and therefore does not pass through the quality control. This results in four acceptable images being available, which are then combined to form the resultant perfusion image. The non-inclusion of the initially processed image that did not satisfy the quality control analysis results in the combined perfusion image having a high image quality, and not being afflicted with motion artifacts.
[0027] An exemplary embodiment based on the procedure illustrated in FIG. 2 is as follows. In a magnetic resonance image for a perfusion study using arterial spin labeling, multiple states of perfusion information-containing images (tag images) and control images are acquired in a 2D or 3D volume, and this procedure is repeated multiple times for averaging so as to increase the signal-to-noise and the contrast-to-noise ratios in the final perfusion image. The tag and control images are acquired interleaved using the arterial spin labeling method tag-control-tag-control-tag, etc. The pairs of tag and control images are subtracted from each other to obtain a subtraction image, which contains only perfusion information. This subtraction image may be afflicted with motion artifacts.
[0028] The initially processed images are then subjected to the quality control review described above, which results in a number of acceptable images passing through the quality control. Only the acceptable images are combined to form the resultant perfusion image.
[0029] An exemplary embodiment of the quality control is illustrated in the flowchart of FIG. 3 . The quality control procedure uses a metric comparison of the initially processed image being analyzed, with reference data. The reference data may be a reference image or a priori determined statistical data. If the comparison (Quality OK?) indicates that the appropriate quality level exists in the initially processed image, it is passed on as an acceptable image.
[0030] The reference data may be dynamically constructed and updated during the ongoing acquisition process, as shown in FIG. 3 .
[0031] The metric comparison between the reference data and the image being analyzed can be based on the mean and/or standard deviation of the intensity distribution, or may be based on an energy analysis such as the root mean square of the energy content of the initially processed image, or may be an edge detection technique employing a grad operator or a Laplace operator, or may be other mutual information contained in a stored image and the initially processed image.
[0032] The quality control procedure can be implemented in real time during the ongoing data acquisition of the image series, or can be done offline using the image series.
[0033] The quality control can be implemented fully automatically or with user interaction. If done with user interaction, the user can manually review each initially processed image in order to pass each image along for making a contribution to the combined perfusion image. Even if the quality control is undertaken in a computerized, automatic manner, without user interaction, it is still possible to notify the user if any, or if a predetermined number, of initially processed images fails to pass through the quality control. This may indicate to the user that adjustments in the image acquisition process need to be made.
[0034] In the quality control procedure, as also indicated in FIG. 3 , an initially processed image which is determined not to satisfy the requisite level of image quality may be analyzed to determine whether a correction by image processing can be undertaken that will result in the image still being suitable for use as an acceptable image for inclusion in the combined perfusion image. If no correction can be done, the initially processed image in question is rejected. If correction can be done, the correction is made and an acceptable image results.
[0035] Although modifications and changes may be suggested by those skilled in the art, it is the intention of the inventor to embody within the patent warranted hereon all changes and modifications as reasonably and properly come within the scope of his contribution to the art. | In a magnetic resonance method and apparatus for generating perfusion images, a perfusion series of magnetic resonance perfusion images is acquired that includes tag images and at least one control image, that are grouped in pairs. From each pair an initially processed perfusion image is obtained, such as by subtraction. Each initially processed image is subjected to a quality control review by analysis with respect to at least one image quality criterion. Any initially processed image that does not satisfy the quality criterion is rejected. Only initially processed images that satisfy the quality criterion are combined to form a resultant magnetic resonance perfusion image. Artifacts in the resultant perfusion image are thereby reduced or avoided. | 0 |
This application is a continuation of U.S. Ser. No. 07/979,592, filed Nov. 20, 1992 now abandoned.
FIELD OF THE INVENTION
The present invention relates to a shock absorber for buffering, by preventing the occurrence of a repulsive force, an impact force developed at the time of connection or disconnection between a chain and a carrier member in a compound trolley conveyor which is used, for example, in an automobile body coating and drying line.
BACKGROUND OF THE INVENTION
According to the prior art, a carrier member (e.g. a flatcar) of a compound trolley conveyor (not shown) is adapted to travel by being pulled with a drive chain through a trolley. The trolley and the drive chain are connected together by a connection means (not shown) which is capable of making engagement and disengagement.
To start the movement of the carrier member when it is at rest, it is necessary that the carrier member be connected to the drive chain which is traveling, using the connection means. Conversely, for stopping the movement of the carrier member when it is traveling, it is necessary to disconnect the carrier member from the drive chain, using the connection means. In the first case, however, since the drive chain which is traveling is suddenly connected to the carrier member which is at rest, the tractive force is sometimes exerted as an excessive impact force on the carrier member.
Therefore, with a view to buffering such impact force, for example the shock absorber (not shown) disclosed in Japanese Utility Model Laid Open No. 30773/1989 (Application No. 125635/1987) is disposed between a foremost trolley and a front trolley in a compound trolley conveyor. The shock absorber is composed of two piston-cylinder mechanisms disposed concentrically face to face with each other and springs which are compressed by the pistons, whereby an impact force is absorbed by compression of the air in each cylinder and compression of the springs.
In such conventional shock absorber, however, since the buffered energy is accumulated in the compressed air and springs and acts as a repulsive force on the pistons, the pistons repeat pulsations reciprocating in the traveling direction and thereafter stop. Consequently, the carrier member vibrates repeatedly in the traveling direction and this repeated vibration may cause damage to the article on the carrier member.
According to the present invention, in order to solve the above-mentioned problem, there is provided a shock absorber in a compound trolley conveyor, including two cylinders disposed between a foremost trolley and a front trolley of the compound trolley conveyor and connected together face to face with each other and two pistons inserted into the cylinders respectively and interconnected, wherein with movement of the pistons, the air in one of the cylinders is compressed and the air in the other cylinder is exhausted.
According to the shock absorber of the present invention, when an impact force is applied to the carrier member at the time of connection or disconnection between the trolley connected to the carrier member and a drive chain, one piston moves in a direction to compress the air in the associated cylinder, while the other piston moves in a direction to withdraw or exhaust air from the associated cylinder. By such air compressing and withdrawing actions, the impact energy is absorbed to buffer the impact force.
The compressed air in one cylinder slowly flows out to the exterior from the piston-cylinder gap, while the outside air slowly flows into the other cylinder through the piston-cylinder gap. Therefore, there is no fear of the impact energy acting as a repulsive force on the piston and hence the impact force is buffered without pulsation of the carrier member.
An embodiment of the present invention will be described below with reference to the drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a sectional view, broken away in the longitudinal direction, of a shock absorber embodying the present invention and shown in the state when a carrier member starts traveling.
FIG. 2 is a view like FIG. 1 but showing the shock absorber in the state when the carrier member is at rest.
FIG. 3 is a schematic front view of a compound trolley conveyor.
FIG. 4 is a plan view of a connecting pipe.
DETAILED DESCRIPTION
First, a compound trolley conveyor (see FIG. 3) in which a shock absorber embodying the invention is provided, will be described.
A carrier member formed as a flatcar 10 of the compound trolley conveyor C comprises a lower frame 12 framed in a square form and having swivel wheels (i.e. casters) 11 mounted to the underside at the four corners; an upper frame 14 also framed in a square shape and provided on the upper surface thereof with support means 13 which support an article carried on the flatcar 10, for example, an automobile body M to be coated; and connecting means 15, 15 for connection of the upper and lower frames 12, 14.
The swivel wheels 11 are required for the flatcar 10 to travel on guide rails (not shown) when moving within a line, e.g. a coating booth B, which requires a stable travel of the flatcar 10.
A chain rail 20 and a carrier rail 30 are laid with difference in height on the floor or the bottom G of a pit formed by cutting out the floor in a channel-like shape.
The chain rail 20 is for movably guiding a drive trolley 22 which moves integrally with a drive chain 21.
The carrier rail 30 is for guiding a foremost trolley 32 which is connected to the drive trolley 22 by a releasable connecting means 31, a front trolley 34 and a rear trolley 35 at the respective front and rear portions of the flatcar 10, and a rearmost trolley 37 which is connected to the rear trolley 35 by a connecting bar 36.
The foremost trolley 32 is connected through a first joint 40 to a connecting bar 41 which in turn is connected through a shock absorber 50 and a second joint 42, to the front trolley 34.
The front and rear trolleys 34, 35 are for the support and conveyance of the flatcar 10. On the rearmost trolley 37 there is provided a disengaging piece or cam 38 which, upon collision with the flatcar 10 by a following or succeeding flatcar (not shown), causes the connection means 31 of the succeeding flatcar to operate and release, thereby disengaging the foremost trolley of the succeeding flatcar from the drive chain 21.
The shock absorber 50 will now be described.
The shock absorber 50 (see FIG. 1) is mounted within the connecting bar 41 which is pipe-like. The connecting bar 41 at its front end is connected to the first joint 40.
The shock absorber 50 is composed of a first cylinder mechanism 60 and a second cylinder mechanism 70 which are formed concentrically and aligned so as to be face to face with each other. That is, the cylinder mechanisms 60 and 70 act in opposite directions.
The first and second cylinder mechanisms 60, 70 are respectively provided with two-stepped cylinders 63 and 73 having small inside diameter bore portions 61, 71 and large inside diameter bore portions 62, 72 and also provided with two-stepped pistons 66 and 76 having small outside diameter portions 64, 74 and large outside diameter portions 65, 75. The piston 76 of the second cylinder mechanism 70 is provided as part of the second joint 42. Between the cylinders 63, 73 and the pistons 66, 76 there are formed gaps (not shown) respectively to permit a limited air flow. These gaps, for example, are typically formed as small annular clearances as defined between the exterior piston wall and the surrounding interior cylinder wall.
The cylinders 63 and 73 are made of brass or bronze, for example.
Although the bores in the first and second cylinder mechanism 60, 70 are of two steps comprising the small diameter portions 64, 74 and the larger diameter portions 65, 75, they may be of only one step, either the small or the large diameter portions.
The two cylinders 63 and 73 are integrally formed concentrically face to face with each other and are connected to the connecting bar 41 and fixed so as not to move in the longitudinal direction of the bar 41 by means of a pin 80 extending through the bar 41.
The two pistons 66 and 76 are connected to a surrounding connecting pipe 82 by engagement of external threads and internal threads. This threaded engagement is prevented from becoming loose by means of four set-screws 81. Between the external and internal threads there usually is formed a gap which permits a limited air flow.
In the connecting pipe 82 there are formed elongated holes 83, 83 in the longitudinal direction of the connecting pipe 82 through which holes the pin 80 extends. The connecting pipe 82, which is formed of carbon steel for example, is interposed between the pistons 66, 76 and the connecting bar 41. The pin 80 is prevented from dislodgement by means of both a nut 84 and a locking pin 85 extending through the pin 80.
The following description is now provided about the operation.
The drive chain 21 moves leftward in FIG. 3 integrally with the drive trolley 22 and is connected through the connecting means 31 with the foremost trolley 32 which is at rest. The foremost trolley 32 then tows the flatcar 10 through the connecting bar 41 and the shock absorber 50, but the flatcar 10 cannot start movement immediately due to its own weight and the weight of the automobile body M.
Therefore, a large tractive force is required, and the cylinders 63, 73 move leftward in FIG. 1 with respect to the pistons 66 and 76 which are at rest, while being pulled by the connecting bar 41. With this movement of the cylinders 63 and 73, the spacing between the foremost trolley 32 and the front trolley 34 expands.
With the aforesaid movement of the cylinders 63 and 73, the internal volume of one cylinder 63 decreases, while that of the other cylinder 73 increases. When the air compression resistance based on such reduction in volume, the air withdrawing resistance based on such increase in volume, and the weight of the flatcar 10 and that of the automobile body M are balanced, the tractive force of the foremost trolley 32 is transmitted to the flatcar 10, so that the flatcar 10 starts moving.
At this time, in the shock absorber 50, the impact energy is absorbed by the air compression resistance and withdrawing resistance in the cylinders 63 and 73 to buffer the impact force exerted on the flatcar 10.
More specifically, the air in cylinder 63, as it is compressed, slowly flows into the connecting bar 41 through the gap between the cylinder 63 and the piston 66 and further through the gap in the threadedly engaged portion between the piston 66 and the connecting pipe 82, as indicated by arrows in FIG. 1. Since the internal volume of the connecting bar 41 is larger than that of the cylinder 63, the internal pressure of the connecting bar 41 will not rise even when the air in the cylinder 63 flows into the connecting bar 41, and so it will not become difficult for the air to flow into the bar 41.
With increase in volume of the other cylinder 73, the outside air slowly flows into the cylinder 73 through the gap in the threadedly engaged portion between the piston 76 and the connecting pipe 82 and the gap between the cylinder 73 and the piston 76, as also indicated by arrows in FIG. 1.
Thus, the air in the cylinder 63 slowly flows out and hence the interior of the cylinder 63 is not held at an increased pressure, whereby the impact energy absorbed by the compressed air will not act as a repulsive force on the pistons 66 and 76.
Consequently, the flatcar 10 starts traveling smoothly without reciprocating motions (pulsation) in the traveling direction.
Lastly, the piston 66 comes into abutment with the cylinder 63, whereby the flatcar 10 is towed by the connecting bar 41 and travels leftward in FIG. 3.
Upon storage or stoppage of a preceding flatcar during travel thereof, the connecting means 31 of a succeeding flatcar abuts the disengaging piece 38 of the preceding car, so that the foremost trolley 32 of the succeeding flatcar is disconnected from the drive chain 21. Thereafter, the foremost trolley 32 of the succeeding flatcar comes into contact in the state of a rear-end collision with the rearmost trolley 37 of the preceding flatcar which is at rest, and the succeeding flatcar stops.
At this time, the succeeding flatcar 10 cannot stop immediately due to its own weight and the weight of the automobile body M, but travels inertially, causing the pistons 66 and 76 to move leftward in FIG. 2 with respect to the stopped cylinders 63 and 73, whereby the spacing between the foremost trolley 32 and the front trolley 34 is narrowed.
With the movement of the pistons 66 and 76, moreover, the internal volume of cylinder 73 decreases, while that of the other cylinder 63 increases.
Due to the compressive resistance and withdrawing resistance of the air in the cylinders 63 and 73 based on such change in volume, the shock absorber 50 causes the flatcar 10 to decelerate and stop without imposing an impact force on the flatcar 10.
During this period, as the compression proceeds, the air in cylinder 73 slowly flows out to the exterior through the gap between the cylinder 73 and the piston 76 and the gap in the threadedly engaged portion between the piston 76 and the connecting pipe 82, as shown by arrows in FIG. 2. Into the other cylinder 63, as its internal volume increases, the air in the connecting bar 41 enters slowly through the gap in the threadedly engaged portion between the piston 66 and the connecting pipe 82 and the gap between the cylinder 63 and the piston 66, as also shown by arrows in FIG. 2.
Since the internal volume of the connecting bar 41 is larger than that of the cylinder 63, the internal pressure of the bar 41 will not significantly drop even when the air in the bar 41 flows into the cylinder 63, so that it will not become difficult for the air in the bar 41 to flow into the cylinder 63.
Thus, the air in the cylinder 73 flows out and therefore the interior of the cylinder 73 is not held in a state of increased pressure, so it is impossible that the impact energy which has been absorbed by the compressed air will act as a repulsive force on the pistons 66 and 76.
Consequently, the flatcar 10 begins to stop slowly without pulsation and stops completely upon abutment of the piston 76 with the cylinder 73 which is at rest.
Although in the above embodiment the two pistons 66 and 76 are connected by threaded engagement to the connecting pipe 82 and are prevented form becoming loose by the four set-screws 81, the threaded portions may be omitted and the two pistons may be merely inserted (not shown) into the two cylinders and connected to the connecting pipe 82 using set-screws. In this case, a gap which permits a limited air flow is formed between the pistons and the connecting pipe.
Further, in the case where the internal volume of the connecting bar 41 is small, small holes 86, 86 may be formed in the connecting bar 41, as indicated by broken lines in FIG. 1, to provide communication between the interior of the bar 41 and the exterior so as not to obstruct the flow of air to or from the cylinder 63.
Since the shock absorber of the present invention has two cylinders in a face-to-face relation (i.e., acting in opposite directions) with each other, the impact force can be buffered under substantially the same conditions in both the case where the carrier member is to be moved and the case where it is to be stopped.
Further, since the air in one cylinder which has been compressed slowly flows out to the exterior through the piston-cylinder gap, the impact energy absorbed by the compressed air will not act as a repulsive force on the piston and therefore it is possible to buffer the impact force without pulsating the carrier member.
In the shock absorber according to this invention, the piston-cylinder arrangements allow rapid pressure build up therein so as to absorb the energy caused by impact of starting or stopping traveling, and the gaps act as flow restrictions so as to allow for controlled flow of air to or from the cylinders so as to reduce the pressure in the cylinder and prevent pressure-induced pulsations in the system.
Additionally, since the oil which is usually employed in this type of shock absorbers is not used in the shock absorber of the present invention, the maintenance is easy and there is no fear of stain; it becomes possible to use the shock absorber even for the oven in the coating/drying line. | A shock absorber in a compound trolley conveyor, including two cylinders disposed between a foremost trolley and a front trolley of the compound trolley conveyor and connected together face to face with each other, and two pistons inserted into the cylinders respectively and interconnected. When an impact force is applied to a carrier member at the time of connection or disconnection between the trolley connected to the carrier member and a drive chain, one piston moves in a direction to compress the air in the associated cylinder, while the other piston moves in a direction to withdraw or exhaust air from the associated cylinder. By such air compressing and withdrawing actions, the impact energy is absorbed to buffer the impact force. The compressed air in one cylinder slowly flows out to the exterior from a piston-cylinder gap, while the outside air slowly flows into the other cylinder through a piston-cylinder gap. | 1 |
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