Source: http://www.google.com/patents/US4987921?dq=6,757,710
Timestamp: 2015-03-27 10:19:13
Document Index: 503337874

Matched Legal Cases: ['art 52', 'art 54', 'arts 55', 'art 54', 'arts 59', 'art 59', 'art 60', 'art 83', 'arts 105', 'arts 105', 'arts 105']

Patent US4987921 - Method of fabricating frozen fine liver piece for artificial liver ... - Google PatentsSearch Images Maps Play YouTube News Gmail Drive More »Sign inAdvanced Patent SearchPatentsA method of fabricating frozen fine liver pieces for an artificial liver which comprises cutting a liver removed from a human being or an animal, from which blood is removed into fine pieces of square shape and freezing the liver pieces with helium gas. A freezing apparatus for an artificial liver which...http://www.google.com/patents/US4987921?utm_source=gb-gplus-sharePatent US4987921 - Method of fabricating frozen fine liver piece for artificial liver, apparatus for freezing the same and freezing vesselAdvanced Patent SearchPublication numberUS4987921 APublication typeGrantApplication numberUS 07/408,111Publication dateJan 29, 1991Filing dateSep 15, 1989Priority dateJan 17, 1984Fee statusLapsedAlso published asCA1245989A1, DE3479088D1, DE3484656D1, EP0150569A1, EP0150569B1, EP0292922A1, EP0292922B1, US4883452, US4984430Publication number07408111, 408111, US 4987921 A, US 4987921A, US-A-4987921, US4987921 A, US4987921AInventorsYoichi Kasai, deceased, Akio Kawamura, Yoshimi Nakanishi, Akira Kakita, Toshihiko Tsuburaya, Yasuo Kuraoka, Nobuo SakaoOriginal AssigneeHoxan CorporationExport CitationBiBTeX, EndNote, RefManPatent Citations (17), Non-Patent Citations (4), Referenced by (2), Classifications (11), Legal Events (5) External Links: USPTO, USPTO Assignment, EspacenetMethod of fabricating frozen fine liver piece for artificial liver, apparatus for freezing the same and freezing vessel
US 4987921 AAbstract
A method of fabricating frozen fine liver pieces for an artificial liver which comprises cutting a liver removed from a human being or an animal, from which blood is removed into fine pieces of square shape and freezing the liver pieces with helium gas. A freezing apparatus for an artificial liver which has gas phase pressurizing means for pressurizing liquid helium coupled to a chamber for storing the liquid helium, a helium gas conduit dipped in the liquid helium passed through the chamber to be closed and contained, in which the liver fine pieces are telescopically received and an exhaust conduit provided with a control valve coupled to the freezing chamber. And, a freezing vessel for an artificial liver which has a flow conduit capable of being coupled to an upper portion and a lower portion of a unit, an upper coupling port and a lower coupling port respectively formed therethrough with closing plugs, two or more mesh plates laterally laid elevationally in the unit, and exit opening in to a containing chamber thus formed.
1. A freezing vessel for fabricating frozen fine liver pieces for an artificial liver comprising:an essentially solid, unperforated cover unit formed of a ceiling plate and a peripheral side wall, the ceiling plate including an upper coupling port extending through the ceiling plate and capable of being selectively coupled with a first coolant flow conduit, or closed by a first plug for transport purposes, the cover unit also including a mesh plate for preventing movement of the fine liver pieces out of the vessel through the upper coupling port, and the peripheral side wall being formed with a lower coupling portion, at least one solid, unperforated hollow coupling cylinder unit including an upper coupling portion selectively detachable from or rigidly connectable to the lower coupling portion of said cover unit, and including a lower coupling portion, and an essentially solid, unperforated bottom unit formed of a bottom plate and a peripheral side wall, the bottom plate including a lower coupling port extending through the bottom plate and capable of being selectively coupled with a second coolant flow conduit, or closed by a second plug for transport purposes, and the peripheral side wall including an upper coupling portion selectively detachable from or rigidly connectable to the lower coupling portion of an adjacent one of the coupling cylinder units; and at least one of the coupling cylinder units or the bottom unit including a laterally positioned mesh plate for supporting the fine liver pieces in the vessel. 2. The freezing vessel as claimed in claim 1, wherein the upper and lower coupling ports are respectively protruded outwardly from the ceiling plate and the bottom plate, the coupling ports are screw-threaded, and the mesh plate in the cover unit is bonded to an inner surface of the ceiling plate laterally across the upper coupling port.
3. The freezing vessel as claimed in claim 1, wherein the lower coupling portion of the cover unit, the coupling portions of each coupling cylinder unit and the upper coupling portion of the bottom unit, are formed with respective mating screw threads so that the cover unit, each coupling cylinder unit and the bottom unit can be screwed together, and each mesh plate for supporting the fine liver pieces is bonded to a downwardly facing stepwise edge formed at a periphery of a peripheral edge wall inner surface of one of the coupling cylinder units or the bottom unit respectively.
4. A freezing vessel for fabricating frozen fine liver pieces for an artificial liver comprising:an essentially solid, unperforated cover unit formed of a ceiling plate and a peripheral side wall, the ceiling plate including an upper coupling port extending through the ceiling plate and being capable of being selectively coupled with a first coolant flow conduit, or closed by a first plug for transport purposes, the cover unit also including a mesh plate for preventing movement of the fine liver pieces out of the vessel through the upper coupling port, and the peripheral side wall being formed with a lower coupling portion, and an essentially solid, unperforated bottom unit formed of a bottom plate and a peripheral side wall, the bottom plate including a coupling port extending through the bottom plate and capable of being selectively coupled to a second coolant flow conduit, or closed by a second plug for transport purposes, the bottom unit also including a laterally positioned mesh plate for supporting the fine liver pieces in the vessel, and also including an upper coupling portion selectively detachable from or rigidly connectable to the lower coupling portion of the cover unit. 5. A freezing vessel for fabricating frozen fine liver pieces for an artificial liver comprising:housing means for receiving the frozen fine liver pieces, an upper coupling port and a lower coupling port on the housing means, each of the upper and lower coupling parts being adapted to be selectively connected to a respective coolant flow conduit, or closed by a respective plug for transport purposes; at least two mesh plates laterally positioned in the housing means in vertically spaced relationship, with at least one of the mesh plates being adapted to support the fine liver pieces for contact with a coolant flowing through the housing means, an opening in a sidewall of the housing means for positioning the fine liver pieces in the housing means, and a cover for opening and closing the opening in the sidewall of the housing means. 6. The freezing vessel as claimed in claim 5, wherein one of the mesh plates which is in an uppermost position is contacted fixedly with an inner surface of an upper part of the housing means for preventing movement of the frozen fine liver pieces out of the upper coupling port.
7. The freezing vessel as claimed in claim 5, wherein the housing means is of essentially solid, unperforated construction.
This is a divisional of application Ser. No. 245,925 filed Sept. 16, 1988, now U.S. Pat. No. 4,883,452, which is a continuation application of Ser. No. 661,469, filed Oct. 16, 1984, abandoned.
Therefore, it has been tried to employ an artificial liver used from a living liver excised externally from an animal. However, when the liver of a dog or a pig is used in this manner, the immunological difference between the liver of the dog or pig and a human being is desirable. A large result cannot be expected in this case. The liver of a baboon has less such problems, but the probability of obtaining the liver of the baboon is difficult.
To this end, the above-described artificial liver is frozen for the preservation, but this method includes removing blood, slicing the excised liver in the millimeter order of thickness, and freezing the sliced livers with liquid nitrogen. When the artificial livers thus obtained are thawed and used for the artificial auxiliary liver device, its urea producing function and glucose producing function as the liver of the artificial livers are extremely smaller than the case that fresh liver is used, finished in a short time, and cannot be expected for sufficient practical effects.
More particularly, the freezing vessel of the invention contemplates to eliminate the difficulties of inconvenience that a mere vessel cannot obtain a desirable result in the instantaneous freezing required particularly for the liver pieces, the quantity of liver pieces contained once in the vessel is limited, cannot be largely increased or decreased, cannot preserve the frozen liver nor be useful for the use after thawing time and another implement must be employed.
FIGS. 8 and 9 show different vessels used for the apparatus, wherein (a) 's illustrate exploded perspective views and (b) 's illustrate assembled perspective views;
FIG. 16 is a front longitudinal sectional view showing the upper portion of the vessel of different embodiment of the invention from FIGS. 13-15.
Then, the liver is dipped in electrolyte out of cells equivalent to the above Ringer's lactate solution simultaneously when the liver is excised, and the liver is then removed from the solution. Preferably, the liver is cut to squares having approx. 3 to 5 mm per side in the solution without removing from the solution, thereby producing a number of liver fine pieces.
In order to measure the function of the liver as the thawed artificial liver for the frozen liver fine pieces preserved as described above, a flask 2 containing 100 m. of 5%-fructose phosphoric acid buffer solution is introduced into a constant-temperature oven 4 for storing hot water 3 of 38� C. as shown in FIG. 1, 30 g. of frozen liver fine pieces 5 frozen by 100 m. of helium gas are filled in the buffer solution 1, 0.1 mg. of ammonium chloride per 1 g. of the liver is filled as a load, and oxygen gas O2 is applied into the solution in the flask 2 through a gas feed conduit 6.
The reasons why the frozen artificial liver provided according to the present invention results in excellent auxiliary liver functions as described above are because the liver is not merely sliced into large thin pieces as in FIG. 4 (a) by the conventional method, but the liver is finely cut into cubes, rectangular prisms or triangular pyramids shown in FIG. 4(b). Thus, only the outer periphery A' of the conventional liver in FIG. 4(a) serves to perform the liver functions, but the central portion A' which occupies the considerably proportion of the entirety shown by the hatched lines does not participate in the liver functions. On the other hand, slight corners of the central portion 5' of the square liver fine pieces of the present invention do not serve to perform the liver functions as shown in FIG. 4(b), and when the blood flow is executed by the artificial auxiliary liver device, the contacting area with the blood of the liver of the invention advantageously increases.
More specifically, a flange 33' of an adiabatic outer tank 33 is mounted on a flange 32 projected from the peripheral side of the freezing chamber 22, the helium gas conduit 24 is movably engaged with an outer tank conduit 34 fastened to the bottom opening of the tank 33, and the lower end of the conduit 34 is sealingly fastened to the helium gas conduit 24, thereby forming an adiabatic gap or chamber 35 around the freezing chamber 22 and the outer peripheral side of the conduit 24 exposed with the outer atmosphere. Then, a vacuum pump 38 is provided through a vacuum evacuating conduit 37 provided with a control valve 36 at the outer tank 33, thereby exhausting gas in the gap 35.
Further, in the embodiment exemplified in FIGS. 6 and 7, an opening 21" provided at the upper port 21' of the chamber 21 and a bottom plate of the tank 33 are coupled via a conduit 39 sheathed on the conduit 34, thereby communicating between a gap 40 between the conduit 39 and the conduit 34 and the gas phase unit A of the chamber 21, and a pressure gauge 41 for measuring the internal pressure of the gas phase unit A is coupled to the conduit 39.
To employ the freezing apparatus thus constructed, liver fine pieces a, a, . . thus finely divided are contained in the freezing chamber 22, and the chamber 22 is closed. In this case, the cover 28 with a packing 29 is used to close the freezing chamber 22. To fasten the cover 28, the cover 28 is clamped by a clamping chain 42 to the freezing chamber 22 as shown in FIGS. 6 and 7. Prior to this clamping, a hanger 45 of a freezing vessel 44 is engaged with a vertical hook rod 43 from an adiabatic insulator B fastened to the cover 28, the vessel 44 is contained in the freezing chamber 22, and the vessel 44 is placed on placing stable arm bases provided in predetermined number at a conical support 46 fastened to the bottom plate 23 of the freezing chamber 22.
Further, as apparent in FIG. 8(a), integral trays 53, 53, . . . of desired number are prepared. The tray 53 is provided integrally with a large-diameter portion 54 and a small-diameter portion 55. The threaded part 52 of the tray 51 is engaged with the threaded part 54' formed on the inner peripheral surface of the large-diameter portion 54, and the threaded parts 55' formed on the outer periphery of the small-diameter portions 55 of the trays 53, 53, . . . of required number are sequentially engaged with the threaded part 54' of the large-diameter portion 53 of next stage, thereby associating the vessels 44 in a manner capable of being disassembled as shown in FIG. 8(a). Then, middle mesh bottoms 56 are respectively extended also on the trays 53, 53, . . . and liver fine pieces a, a, . . . to be frozen are placed on the middle bottom 56 and the middle mesh bottom 49 of the tray 51 therein.
Next, the freezing vessel 44 exemplified in FIG. 9 will be described in detail. A mesh bottom board 58 is extended on the bottom of a vessel body 57 shown in FIG. 9(a), and the liver fine pieces a, a, . . . are contained in the vessel body. Threaded parts 59 and 60 are respectively formed on the upper and lower outer peripheries of the body 57, an upper cover 61 formed with the hanger 45 is engaged with the threaded part 59, and a lower cover 62 is engaged with the threaded part 60. Thus, the freezing vessel 44 shown in FIG. 9(b) is constructed. An outflow cylinder 63 and an inflow cylinder 64 are respectively protruded longitudinally from the centers of the upper and lower covers 61 and 62 to pass helium gas to the vessel 44 as will be described in detail.
As described above, the freezing vessel 44 which has readily contained liver fine pieces a, a,. . . cut in square of several mm in side is mounted in the freezing chamber 22, the chamber 22 is closed by the cover 28 as described above, the pressurizing means 26 is operated to raise the internal pressure of the chamber 21 to a predetermined pressure (e.g., approx. 600 mmAg), and the pressure is confirmed by the pressure gauge 41.
When the internal pressure of the chamber 21 is raised to a predetermined pressure as described above, the control valve 30 provided in the conduit 29 is manually or automatically opened, and the conduit 29 is opened with the outer atmosphere.
Thus, helium is gasified from the surface of the liquid helium in the conduit 24, and raised. After the freezing chamber 22 is filled with the helium gas, the helium gas is exhausted from the conduit 29 thus opened into the atmosphere. Then, the liver fine pieces a, a, . . . contained in the freezing chamber 22 are instantaneously frozen in contact with the helium gas in this case.
As exemplified by the above-described second embodiment of the apparatus of the invention, the gas phase pressurizing means 26 for pressurizing the liquid helium 20 is coupled to the chamber 21 for storing the liquid helium 20, the helium gas conduit 24 dipped in the liquid helium 20 is passed through the chamber 21 to allow the conduit 24 to communicate with the freezing chamber 22 to be closed and contained, in which the liver fine pieces a, a, . . . are telescopically received, and the exhaust conduit 29 provided with the control valve 30 is coupled to the freezing chamber 22. Therefore, the helium gas abruptly gasified from the liquid helium and incoming to the freezing chamber 22 for containing the liver fine pieces a, a, . . . is supplied to and passed through the freezing chamber 22. Thus, the helium gas can be rapidly and uniformly contacted with the liver fine pieces contained in the freezing chamber 22. Therefore, the liver fine pieces can be uniformly frozen instantaneously at the helium temperature, and are frozen with necessary and sufficient consumption amount of the helium gas. Consequently, a freezing apparatus which has no waste of helium gas can be provided.
A third embodiment as a freezing vessel used to execute the method of the first embodiment of the invention will now be described in detail with reference to FIGS. 10 to 12. The vessel is slightly similar to that in FIG. 9, but this vessel is composed at least of a cover unit 70 and a bottom unit 71, as well as one or more of coupling cylinder units 72, 72, . . associated between the cover unit 70 and the bottom unit 71, which may be preferably formed of members made of synthetic resin such as Teflon.
The cover unit 70 is of an essentially solid, unperforated construction being formed of a ceiling plate 73, and a peripheral side wall 74 in a tray shape, an upper coupling port 75 is passed at the center of the ceiling plate 73, and the port 75 is closed by a mesh plate 76 bonded to the inner surface of the ceiling plate 73.
A lower couping portion 79 is provided at the peripheral side wall 74. In the exemplified example in the drawings, the coupling portion 79 is formed of female threads, and the bottom unit 71 or the coupling cylinder units 72, 72 are detachably coupled thereto as will be described in detail.
Further, the bottom unit 71 also is of an essentially solid, unperforated construction, being formed of a bottom plate 80 and a peripheral side wall 81 as apparent in FIGS. 11 and 12, and a lower coupling port 82 is provided through the center of the bottom plate 80. In the embodiment exemplified in the drawings, the coupling port 82 is protruded downwardly similar to the coupling port 75, a coupling threaded part 83 is formed on the outer periphery thereof, and a plug 78' or a flow conduit may be coupled thereto.
The cylinder units 72, 72, . . . used as required are formed in a solid, unperforated, hollow cylindrical shape, a mesh plate 88 for placing is bonded to the lower stepwise edge 87 formed in the middle height in the same manner as the case of the bottom unit 71, is elevationally formed in the cylinder units 72, an upper coupling portion 89 of male threads is formed on the upper outer periphery reduced in diameter, and a lower coupling portion 90 of female threads is formed on the lower inner periphery of the same diameter as the coupling portion 89.
In case of FIG. 11, the cover unit 70 is not coupled directly to the bottom unit 71, but a lower coupling portion 90 of the cylinder unit 72 is threaded with an upper coupling portion 86, the liver fine pieces are contained also on the placing mesh plate 72 of the unit 72, and the coupling portion 90 of the other cylinder unit 72 is threaded with the upper coupling portion 89 of the cylinder unit 72, thereby coupling the two cylinder units 72 in double manner to thread the cover unit 70 with the cylinder unit 72 of the uppermost stage. In this case, four times the liver fine pieces of FIG. 12 may be simultaneously frozen.
When the frozen liver fine pieces thus preserved as described above are further to be used, the plugs 78, 78' are removed, the frozen liver fine pieces are thawed by predetermined means. Then, flow conduits in the artificial auxiliary liver device are respectively coupled to the upper and lower coupling ports 75, 82, and the auxiliary liver device is then operated to pass the patient's blood to the liver pieces and to then return the blood to the patient.
Further, the quantity of the liver fine pieces to be frozen once can be increased or decreased by coupling only the cover unit 70 and the bottom unit 71 or by interposing the coupling cylinder units 72 in the desired number. Particularly in case of using the liver fine pieces after thawing as described above, the flow of the blood can be controlled corresponding to whether the patient is adult or child who used the artificial auxiliary liver device as increased or decreased as described above. Further, for preservation or transportation, the vessel can be readily handled conveniently by the use of the plugs 78, 78'. The frozen liver fine pieces might not be unintentionally discharged from the vessel by arranging the mesh plate 76, and can be used by connecting the vessel to the artificial auxiliary liver device. Consequently, another vessel for this purpose need not be prepared.
A fourth embodiment of the freezing vessel according to the present invention will be described in detail with reference to FIGS. 13 to 16. A housing unit 100 formed in a cylinder and made of synthetic resin such as Teflon, is formed respectively with an upper coupling port 103 and a lower coupling port 104 at the centers of the upper and lower portions 101 and 102 therethrough.
In the embodiment exemplified in the drawings, the coupling ports 103 and 104 are not only protruded upwardly and downwardly, but coupling threaded parts 105 and 106 are respectively formed as male threads on the outer peripheries thereof. Thus, in case that blood is flowed to be described later, a flow conduit is coupled by threading to the coupling ports 103, 104 or plugs 107, 107' are engaged as designated by one-dotted chain lines in FIG. 14, and can be closed. In this case, it is noted that the coupling threaded parts 105, 106 are not formed, but a mere engagement means may be employed for coupling therebetween, or the threaded parts 105, 106 may be formed as female threads in the same manner as the third embodiment as described above.
In the unit 100, two or more mesh plates 108, 108, . . may be laid elevationally, thereby forming containing chambers 109 of predetermined number. In FIGS. 13, 14, a containing chamber 109 is formed of only two mesh plates 108, 108. However, in the embodiment in FIG. 15, five mesh plates 108, 108, . . . are laterally laid to form four containing chambers 109, 109, . . .
As laterally laying means of the mesh plates 108, 108, as exemplified in the drawings, the mesh plates 108, 108 are engaged with the supporting grooves 112 of the supporting projecting strips 111, 111, . . . projected on the inner surface of the peripheral side wall 110 of the unit 100. In this case, since the mesh plate 108 of the uppermost stage does not place the liver fine pieces a, a, . . . thereon as will be described later, the mesh plate 108 may employ, as shown in FIG. 16, a small mesh plate may be bonded fixedly on the upper inner surface of the unit 100 to close the upper coupling port 103.
Further, in this embodiment, exits 113 may be opened at the position corresponding to the containing chambers 109, 109, . . . , and a cover 114 openably closed on the exit 113 may be provided.
To use the freezing vessel of this embodiment, the cover 114 is opened, the liver fine pieces a, a, . . . to be frozen are introduced from the exit opening 113, which is in a sidewall of the housing unit 100, placed on the mesh plates 108, 108, . . . except the mesh plate of the uppermost stage, the cover 114 is then closed, and a refrigerant supply conduit, not shown, is coupled to the lower coupling port 104.
Thus, the refrigerant such as gaseous helium is introduced into the unit 100, and then discharge from the upper coupling port 103 externally. In this case, the liver fine pieces a, a, . . . on the mesh plates 108, 108, . . . are instantaneously frozen entirely in contact with the refrigerant.
In the fourth embodiment exemplified in the drawings, the flow conduit is capable of being coupled to the upper portion 101 and the lower portion 102 of the unit 100, the upper coupling port 103 and the lower coupling port 104 are respectively formed therethrough to close the plugs 107, 107', two or more mesh plates 108, 108', . . . are laterally laid elevationally in the unit 100, the exit 113 is opened corresponding to the containing chamber 109 thus formed, and the exit opening 113 is capable of being opened by the cover 114. Therefore, the refrigerant introduced from the lower coupling port 104 is discharged from the upper coupling port 103, thereby enabling to contact the refrigerant with the liver fine pieces on the mesh plates. Consequently, the liver fine pieces can be instantaneously frozen as desired.
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