WO1988003045A1 - Separation cryogenique amelioree de globuline - Google Patents
Separation cryogenique amelioree de globuline Download PDFInfo
- Publication number
- WO1988003045A1 WO1988003045A1 PCT/US1987/002899 US8702899W WO8803045A1 WO 1988003045 A1 WO1988003045 A1 WO 1988003045A1 US 8702899 W US8702899 W US 8702899W WO 8803045 A1 WO8803045 A1 WO 8803045A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- vessel
- plasma
- nipple
- cryoprecipitate
- body portion
- Prior art date
Links
- 238000000926 separation method Methods 0.000 title claims description 25
- 108010091326 Cryoglobulins Proteins 0.000 title description 8
- 210000002445 nipple Anatomy 0.000 claims abstract description 40
- 239000000463 material Substances 0.000 claims description 20
- 239000012530 fluid Substances 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 238000003032 molecular docking Methods 0.000 claims description 9
- 230000008014 freezing Effects 0.000 claims description 7
- 238000007710 freezing Methods 0.000 claims description 7
- 230000001413 cellular effect Effects 0.000 claims description 6
- 230000012953 feeding on blood of other organism Effects 0.000 claims description 6
- 238000010257 thawing Methods 0.000 claims description 6
- 238000012546 transfer Methods 0.000 claims description 6
- 238000001125 extrusion Methods 0.000 claims description 5
- 230000002209 hydrophobic effect Effects 0.000 claims description 5
- 239000010836 blood and blood product Substances 0.000 claims description 4
- 229940125691 blood product Drugs 0.000 claims description 4
- 238000013022 venting Methods 0.000 claims description 3
- 230000000717 retained effect Effects 0.000 claims description 2
- 238000004891 communication Methods 0.000 claims 2
- 210000000170 cell membrane Anatomy 0.000 claims 1
- 238000012864 cross contamination Methods 0.000 claims 1
- 238000002955 isolation Methods 0.000 abstract description 13
- 210000002381 plasma Anatomy 0.000 description 52
- 210000004369 blood Anatomy 0.000 description 17
- 239000008280 blood Substances 0.000 description 17
- 238000012545 processing Methods 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 6
- 239000012528 membrane Substances 0.000 description 4
- 238000007789 sealing Methods 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 3
- PYHRZPFZZDCOPH-QXGOIDDHSA-N (S)-amphetamine sulfate Chemical group [H+].[H+].[O-]S([O-])(=O)=O.C[C@H](N)CC1=CC=CC=C1.C[C@H](N)CC1=CC=CC=C1 PYHRZPFZZDCOPH-QXGOIDDHSA-N 0.000 description 2
- 108010080379 Fibrin Tissue Adhesive Proteins 0.000 description 2
- 208000031220 Hemophilia Diseases 0.000 description 2
- 208000009292 Hemophilia A Diseases 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000013011 mating Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004800 polyvinyl chloride Substances 0.000 description 2
- 229920000915 polyvinyl chloride Polymers 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000037029 cross reaction Effects 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940127554 medical product Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
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- 238000001556 precipitation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000000565 sealant Substances 0.000 description 1
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- 238000010561 standard procedure Methods 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
- B04B—CENTRIFUGES
- B04B5/00—Other centrifuges
- B04B5/04—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers
- B04B5/0407—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers for liquids contained in receptacles
- B04B5/0428—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers for liquids contained in receptacles with flexible receptacles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/02—Blood transfusion apparatus
- A61M1/0209—Multiple bag systems for separating or storing blood components
- A61M1/0218—Multiple bag systems for separating or storing blood components with filters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/02—Blood transfusion apparatus
- A61M1/0209—Multiple bag systems for separating or storing blood components
- A61M1/0231—Multiple bag systems for separating or storing blood components with gas separating means, e.g. air outlet through microporous membrane or gas bag
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3693—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits using separation based on different densities of components, e.g. centrifuging
Definitions
- This invention relates to blood separation methods and apparatus, and more particularly to the isolation of cryoprecipitate or cryoglobulin.
- Cryoprecipitate isolated from blood plasma, is rich in clotting factors. For this reason, it has long been used for the treatment of hemophilia. More recently, it has been proposed to make a "fibrin glue" for sealing surgical joins using a multi-part mixture of cryoprecipitate, thrombin and calcium chloride. Cryoprecipitate alone has also been reported as suitable for such use, especially as a natural clotting sealant around sutured joins of arterial or veinous tissue. Although of lesser tensile strength than a fibrin glue composition, approximately 2 to 3 percent of plasma may be isolated as cryoprecipitate, and the isolation may be performed in a hospital blood bank. Thus, autologous aliquots of "cryo" for surgical use may be prepared. This offers great promise in heart surgery, where suture bleeding, and patient cross reactions to blood-derived agents are both particularly grave problems.
- the standard procedure for isolating cryoprecipitate uses a conventional phlebotomy set.
- the blood is drawn and anticoagulated, and centrifuged to separate the plasma.
- the plasma is expressed to the plasma bag, which is then sealed.
- the plasma bag is then frozen and thawed, which results in the precipitation of cryoprecipitate as a whitish factor.
- the cryoprecipitate is then separated from the plasma. This may be done by centrifuging the plasma bag, and expressing the lighter cryo-poor fraction from the bag, leaving the cryoprecipitate fraction of 4 - 8 milliliters in the bag.
- the thawed plasma may be centrifuged in one or more centrifuge tubes, isolating the cryoprecipitate as a highly viscous plug in the bottom of each tube.
- the separated material may be used by daubing about a surgical site with a spatula, or may be refrozen and thawed to result in a thinner, injectable form of cryoprecipitate such as used for the aforementioned treatment of hemophilia.
- cryoprecipitate having a hollow cylindrical vessel with a first closed end, a second end and a longitudinal axis, the first end having a port with a sterile docking connector for transferring plasma between the vessel and a plasma bag, and the second end having a generally contoured face with a nipple extending from and closing the second end.
- the nipple has a generally cylindrical shape and encloses a volume of approximately 2 to 5 percent of the volume of the vessel.
- the vessel is formed of a semi-rigid material and the first end is closed by a cap containing a microporous filter for venting the vessel during transfer of plasma through the port.
- the nipple has a tip portion which may be sliced off to permit extrusion of the isolated cryoprecipitate by squeezing the vessel.
- the nipple has a twist-lockable connector, such as a Luer fitting, for attachment to a syringe or to an applicator tip.
- a presently preferred embodiment includes plural vessels, each with an end cap and a nipple, wherein all the end caps are connected to a common sterile docking connector. The total volume of the plural vessels is approximately 250 to 350 milliliters, for holding the plasma from one unit of whole blood.
- a port located above the nipple allows non-turbulent decanting of separated fluid
- a filter chamber located within the vessel may receive a charge of cellular fluid through an additional port. When its cells are frozen and thawed during processing, the released fluids are filtered through the chamber into the plasma contained in the vessel.
- a method for the isolation of cryoprecipitate according to the invention includes the steps of separating plasma from whole blood, transferring the plasma to the one or more vessels according to the invention, freezing and thawing the plasma, and centrifuging the vessels to isolate the cryoprecipitate in the nipple end of each vessel.
- the cryo-poor plasma is decanted from each vessel through its port, and the vessels, each with a plug of cryoprecipitate in its nipple end, are stored as sterile aliquots for surgical or medical use.
- the cryoprecipitate is applied directly to a surgical site by extruding it from the nipple.
- Figure 1 is a schematic illustration of the invention with a plasma bag of a phlebotomy set
- Figures 2A, 2B show a plan view from above, and a vertical section, respectively, of the set of Figure 1 in a support fixture for centrifuging;
- Figure 3 shows a schematic section of a preferred embodiment of a three-vessel sterile docking set
- Figure 4 shows a section of another embodiment of the invention
- FIG. 5 shows another embodiment of the invention with an integral extrusion mechanism
- Figure 6 shows a longitudinal cross-section of another embodiment of a cryoglobulin separation vessel
- Figure 7 shows a detail of a radial section of the vessel of Figure 6;
- Figure 8 shows a longitudinal cross-section of another separation vessel
- Figure 9 shows a flexible embodiment of a separation vessel.
- FIG. 1 shows a schematic illustration of a set 1 according to a basic embodiment of the invention.
- Set 1 includes a plurality of vessels 10 each having an inlet end 12 with a port 14.
- a branch tube 16 runs from each port 14 to a common tube 17 which connects to a plasma bag 18.
- the plasma bag 18 may be the plasma receiving bag of a conventional phlebotomy set, and tube 17 may connect in a conventional manner to such bag so as to form a sterile system.
- the entire set including bag 18 tubes 17, 16 and vessels 10 may be formed as a sterile sealed unit.
- tube 17 connects to plasma bag 18 via a spike or other fitting 20, which is preferably a sterile docking fitting.
- Each vessel 10 has a generally cylindrical body 20 which extends from an inlet cap 12 which closes one end to a collection end 22 with the shape of a small substantially cylindrical nipple which closes the other end of the cylinder.
- the nipple structure is located to receive the densest faction of plasma during centrifuging, and is dimensioned to accommodate the amount of cryoprecipitate yielded by the volume of plasma held by the vessel 10.
- FIGS 2A, 2B show a top perspective view and a section, respectively of a four vessel set according to Figure 1 held in a support fixture for centrifuging.
- Vessels 10 are each inserted in a cylindrical well 32 of the fixture 30, and tubes 16,
- FIG. 18 have been expressed into the vessels 10 and bag 18, which is empty, is rolled up and inserted in another recess 34 of fixture 30.
- Figure 2B is a vertical section along the planes indicated in Figure 2A, through the fixture 30 and passing through two of the recesses 32.
- the cylindrical wells 32 of the fixture 30 have solid walls defining a contour identical to that of the vessels 10 so that each vessel is rigidly supported about its entire outside surface.
- a cover plate 35 having slots for the passage of tubes 16, 17 therethrough may be fitted over the fixture in the centrifuge bucket so as to provide a complete pressure resisting housing around the set during centrifuging.
- the method of separating cryoprecipitate according to the invention proceeds as follows. First, after blood is drawn, anticoagulated and separated, the plasma is expressed off into a plasma bag 18. The plasma is then expressed into the vessels 10 which are dimensioned to receive the entire volume of plasma from one unit of whole blood. According to standard blood bank practice in the United States, a unit of whole blood has a blood volume of about 450 milliliters, and yields 200 - 300 or more milliliters of plasma. Thus, for example, there may be four vessels 10 each having a volume of approximately 60 milliliters, three vessels each having a volume in the range of 80 milliliters or even a single large 250 milliliter vessel.
- the plasma is frozen and then thawed to precipitate out the cryoprecipitate.
- a good yield is obtained by completely freezing to minus thirty degrees C, thawing in a refrigerator at two to six degrees C and centrifuging at two to five thousand g (RCF) for ten to thirty minutes.
- Vessels 10 and the empty plasma bag 18 are then placed in the fixture 30 described above and centrifuged at a speed and for a time sufficient to separate out the cryoprecipitate as a viscous mass in the nipple 22.
- the centrifuge is then stopped, the vessels 10 and bag 18 removed therefrom, and the cryo-poor plasma faction is decanted from each vessel back into the plasma bag 18, whence it may be returned to the donor or otherwise used.
- Each vessel 10 then contains one aliquot of cryoprecipitate from its corresponding volume of plasma.
- cryoprecipitate With a unitary set as shown in Figure 1, or a tubing and vessel set adapted for sterile docking, the units of cryoprecipitate thus isolated will be sterile and may be banked for surgical use.
- cryoprecipitate since the separation is accomplished using a normal blood bank centrifuge with the set 1 and fixture 30, cryoprecipitate may be prepared from a patient's own blood in preparation for a surgical procedure on the patient weeks in advance, substantially lessening the risks of infection or rejection reactions inherent in the use of pooled blood products or in the use of blood products from other donors.
- FIG. 3 shows a partial view and section of a preferred embodiment of a three vessel sterile docking set for the isolation of cryoprecipitate according to the invention.
- a capped bag spike 20 connects to tube 17 which communicates via a trifurcated adaptor manifold 19 to three tubes 16, which extend to respective collection vessels 40.
- a suitable adaptor manifold 19 is a Medex part no. B-1450-09.
- Each vessel 40 has a generally cylindrical body 45 with a cap 42 at one end and a nipple portion 50 at the other end.
- Body 45 is preferably formed of a semi-rigid material such as a thick walled polyvinyl chloride plastic, and has an interior volume in the range of 60 to 80 milliliters.
- End cap 42 is formed with an inlet port 44 and also a vent 46 which permits the displacement of air when plasma is transferred from a plasma bag to the vessel or vice versa.
- Vent 46 includes a hydrophobic microporous filter 48 having a pore size in the range of .45 microns for preventing the influx of contaminants while permitting gas to vent therethrough.
- a suitable filter is a membrane-type filter sold by the Burron Medical Products company of Pennsylvania as their filter membrane, part no. A-700 4020.
- Cap 42 is cemented or otherwise bonded to body 45 for sealing the end thereof.
- nipple end 50 which has a generally cylindrical or substantially tubular shape and is dimensioned so as to have an interior volume in the range 2 to 5 percent of the volume of the body 45.
- Nipple 50 extends to an outlet end which is adapted for connection to a separate device for transfer of the separated cryoprecipitate or for direct application of the separated precipitate to a surgical site.
- nipple 50 has an interior wall 51 at its extreme tip which is tapered as a female Luer lock so that a syringe may be directly attached to the tip to draw out the separated precipitate and to allow a surgeon to use a syringe as an applicator of the precipitate to a surgical site.
- Nipple 50 has an external wall 52 which is threaded as a male twist-lock connection, i.e., a male Luer fitting.
- Nipple 50 is thus also adapted for directly connecting to a twist lockable cannula or needle for directly extruding the cryoprecipitate onto a surgical site.
- a Luer lock cap 53 such as the Luer cap part no. B-1500-30 sold by the Medex company of Ohio having a twist-lock inner surface 54 closes the end of the nipple so that the entire set comprising vessel(s) 40 with spike and supply tubes 16, 17 constitutes a sterile closed system.
- FIG. 4 shows another embodiment of the invention having vessels 60, in a similar sectional view.
- Two vessels are shown connected to a common manifold 19 and supply tube 17. Although two vessels are shown, one, or any number (n) may be used.
- vessel 60 includes a cylindrical body 65 having a volume of approximately 250/n milliliters, and tapering at wall 67 to a nipple portion 70.
- Nipple portion 70 has a conically pointed nose 72 which may be sliced off, in the manner of caulking cartridge, so as to provide an outlet for the separated cryoprecipitate therein.
- Vessel 60 is formed of a semi-rigid but sufficiently flexible material, such as a .030 to .040 inch thick flexible PVC, so that with the inlet tube 16 sealed closed, the vessel 60 may be squeezed by hand to extrude the precipitate from the end 72 of the vessel.
- the conical end has a taper of approximately fifteen degrees, terminating in a tip having an inner spherical radius in the range of (.05) to (0.10) inches, thus providing both a high degree of operator visibility, and a fine extrusion filament of precipitate when so squeezed.
- vent structure is shown, although a vent similar to the structure 46, 48 of Figure 3, or a simple return breather tube extending from the vessel 60 to the plasma bag may be employed during the plasma filling and separating steps. Such tube or other vent is then sealed, clamped or capped prior to using the vessel 60 as a pressurized extruding device.
- FIG. 5 shows yet another embodiment of a vessel 80 according to the invention having a body 85 and a nipple portion 90.
- nipple 90 has an open tip with an inner surface 91 and an outer surface 92 configured for twist lockable connection to a mating Luer fitting.
- a cap 93 closes the end.
- the body of vessel 80 is formed of a substantially rigid material such as a polycarbonate plastic, and has an end cap 82 which includes, in addition to a vent 86 and an inlet port 84, a hermetically mounted piston structure 83.
- Piston structure 83 includes a soft rubber or similar piston 87a having a shank 87b which extends through the cap 82 and is hermetically sealed by a removable lock cap 84. Piston structure 83 is centered over the cylindrical nipple 90. A separate plunger 88 is provided, and after separation of the cryoprecipitate, the supply tube 16 may be severed and sealed so that the vessel 80, containing a sterile aliquot of cryoprecipitate, may be stored and used directly as a surgical applicator.
- Shank 87b may be fashioned as a break-away portion of the cap, or as a flexible stopper-like fitting which is driven through from a sealing position in a mating hole in the cap by plunger pressure.
- FIG. 6 shows a cross-sectional view of another embodiment of a vessel 100 for the separation of cryoglobulin according to applicant's invention.
- Vessel 100 has a cap portion 102, a body portion 104, and a nose portion 106.
- vessel 100 has a volume for accommodating the plasma from one unit of blood, or approximately 300 cc.
- the nose portion 106 encloses an interior volume 105 which serves as a cryoglobulin receiving sump of approximately ten cc, and the entire container is formed with substantially rigid or semi-rigid walls.
- the body portion 104 has a generally cylindrical wall portion 104a which defines a generally cylindrical plasma reservoir, and also has a generally conical wall portion 104b extending therefrom to the sump 105.
- sump 105 has a diameter of approximately .8 inches, and the tapered wall portion 104b assures that the interface, after centrifuging, between the separated cryoprecipitate and the plasma has a relatively small area. This helps prevent remixing during post processing operations such as decanting the plasma.
- Vessel 100 is equipped with three ports.
- a first port 108 is located at the tip of the nose portion, and is used in operation for access for the separated cryoglobulin after processing has been completed. This port may have a Luer fitting or other connector as described in relation to the previously described vessel embodiments.
- a second port 110 enters the vessel in the tapered wall portion 104b just above the receiving sump.
- a third port 112 is centrally located in the cap 102, and may serve as a vent during the filling and unfilling of the vessel. Port 112 contains a bacterial hydrophobic filter, and may be capped during centrifuging, as required.
- the embodiment of Figure 6 permits the plasma to be decanted from the central port 110 located just above the plasma/cryoprecipitate separation line after processing.
- the vessel need not be inverted (as is the case for the vessels 20 of Figure 1), so that air does not percolate through the fluid during any processing stage.
- vessel 100 is preferably formed with a longitudinally extending groove or trough 111 which extends between the upper edge of sump 105 and the lower inside edge of the opening to port 110. This groove or trough 111 is illustrated in cross-section in Figure 7.
- It serves as a drainage channel through which, when the vessel is slightly tilted toward port 110, the separated plasma near the sump interface can flow without introducing turbulence and remixing at the separation line. This permits the plasma to be substantially completely decanted after processing, resulting in a clear separation of product.
- FIG 8 shows a cross-sectional view, similar to that of Figure 7, of yet a further embodiment of a separation vessel 120 according to the invention.
- Parts of vessel 120 are numbered identically to corresponding parts of vessel 100.
- Vessel 120 contains, in addition, a hollow interior column 122 communicating with an outlet port 124 and preferably also a vent 126, with elements 122, 124 and 126 all mounted on the cap portion 102.
- Hollow column 122 has a plurality of apertures 130 at its lower end, and is filled with packing material 132 which provides a filtration matrix for fluids passing therethrough.
- a microporous filter element 133 may be used.
- a further vent 134 is provided in the cap 102.
- the vessel of Figure 8 permits the addition of biological material via port 124 into the column 122 for processing with the cryoglobulin.
- vessel 120 One specific application of vessel 120 which applicant envisages is that platelet rich blood products may be placed in column 122 and thus may be subjected to the freezing and thawing protocols described above for the isolation of cryoprecipitate. Such freezing is expected to rupture the platelet membranes so that upon subsequent centrifuging, cellular products contained within the platelets will pass through the filtration matrix 132 into the cryoprecipitate, while the cellular membrane material will be effectively filtered out and retained within the column by the filter. Thus, vessel 120 may be used to prepare cryoprecipitate enriched with platelet growth factor, to promote enhanced recovery in topical surgical applications of cryo-glue or the cryoprecipitate as described above.
- FIG. 9 shows a further embodiment of a separation vessel 140 which is similar in some respects to vessel 100 of Figure 6.
- Vessel 140 differs in being formed as a flat bag, rather than a rigid or semi-rigid container. Vessel 140 requires no hydrophobic filters or other provision for accommodating changes of volume.
- components corresponding to elements of vessel 100 are identically numbered.
- the harvesting outlet port 108 is shown in some detail, and includes an exit tube 141 adapted to connection with a applicator or transfer device, a membrane 142 sealing the exit port during processing, and a break-away cover 143 which maintains the exit tube sterile prior to use.
- Bag 140 is formed with RF welded seams 145 of sufficient strength and has apertures 146 at the top for hanging in a centrifuge bucket.
- a third port 148 which communicates with an inner bag 150 having matrix packing material 152 therein.
- Elements 148, 150, 152 are optional elements and are intended to serve the same function as described above for the platelet enrichment processing vessel 120 of Figure 8.
- vessel 140 is adapted for insertion into a centrifuge bucket having a substantially rigid liner forming a recess having the shape of vessel 100 or 120, and that vessel 140 is of a size tailored to assume that shape during centrifuging.
- the vessels 100, 120, 140 are preferably fabricated and sterilized together with one or more blood bags so as to form an integral phlebotomy set for drawing blood, and storing and processing the cryoprecipitate in an entirely closed and sterile environment.
- one or more auxiliary bags are preferably attached to one or more of the ports 110, 112, 148 for the initial drawing of blood and separation of plasma therefrom for provision to the vessel, and for drawing off the cryoprecipitate-depleted plasma from the vessel following the above described processing.
- Each of the above described embodiments thus preferably either includes a closed sterile phlebotomy set, or is adapted for docking with the plasma bag of a sterile set.
- the invention provides for the sterile isolation of cryoprecipitate in a form which may be stored. It also provides a vessel which may be used directly as an applicator in a surgical setting.
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- Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- External Artificial Organs (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Un assemblage (1) d'isolation d'un cryoprécipité comprend un récipient creux (10) ayant une première extrémité fermée (12), une deuxième extrémité et un axe longitudinal. Un embout (22) allongé ferme la deuxième extrémité et renferme environ 2 à 5 % du volume du récipient creux.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US925,318 | 1986-10-31 | ||
US06/925,318 US4917804A (en) | 1986-10-31 | 1986-10-31 | Method and vessel for separation of cryoglobin |
US07/081,484 US4915847A (en) | 1987-08-04 | 1987-08-04 | Cryoglobulin separation |
US081,484 | 1987-08-04 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1988003045A1 true WO1988003045A1 (fr) | 1988-05-05 |
Family
ID=26765623
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1987/002899 WO1988003045A1 (fr) | 1986-10-31 | 1987-10-30 | Separation cryogenique amelioree de globuline |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP0335882A4 (fr) |
JP (1) | JPH02501356A (fr) |
WO (1) | WO1988003045A1 (fr) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0499891A1 (fr) * | 1991-02-19 | 1992-08-26 | Pall Corporation | Système de filtrage du sang |
EP0509054A4 (en) * | 1990-01-03 | 1993-07-28 | Cryolife, Inc | Preparation of fibrinogen/factor xiii precipitate |
US5891327A (en) * | 1996-07-10 | 1999-04-06 | Axygen, Inc. | Centrifuge tube with rotational position index |
WO2003008012A3 (fr) * | 2001-07-18 | 2003-04-03 | Hiberna Ag | Procede et dispositif de preparation du sang |
EP3213802A3 (fr) * | 2016-03-02 | 2017-11-22 | The Boeing Company | Systeme rotatif pour enlever du gas d'un agent d'étanchéité |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4983204B2 (ja) * | 2006-10-27 | 2012-07-25 | ニプロ株式会社 | 遠心分離容器及び遠心分離方法 |
EP2174676B1 (fr) * | 2007-07-30 | 2016-01-27 | JMS Co., Ltd. | Appareil pour séparer et stocker des composants du sang |
US8721617B2 (en) | 2009-02-04 | 2014-05-13 | Jms Co., Ltd. | Liquid component collecting device |
JP5322790B2 (ja) * | 2009-06-15 | 2013-10-23 | 川澄化学工業株式会社 | 血液成分のサンプリングシステム及び血液成分のサンプリング方法並びに採血管 |
JP5955353B2 (ja) * | 2014-07-23 | 2016-07-20 | みゆき 山川 | 体液収容器 |
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US3481712A (en) * | 1959-11-20 | 1969-12-02 | Clay Adams Inc | Sediment container and cap and analysis technique |
US3897902A (en) * | 1974-02-01 | 1975-08-05 | Sindco Corp | Phase separating tube |
US3986506A (en) * | 1974-09-03 | 1976-10-19 | Baxter Travenol Laboratories, Inc. | Apparatus for separation of cryoprecipitate from blood plasma and method |
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US4483825A (en) * | 1982-07-09 | 1984-11-20 | Fatches Keith R | Pipette and filter combination |
US4698311A (en) * | 1985-10-30 | 1987-10-06 | Ortho Diagnostic Systems Inc. | Particle washing and separation method |
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DE1171178B (de) * | 1960-02-06 | 1964-05-27 | Martin Christ Fa | Zentrifugenzelle |
US4066414A (en) * | 1977-02-15 | 1978-01-03 | Donald Selby | One piece tube and microscope slide manipulative laboratory device |
DE3238471C1 (de) * | 1982-10-16 | 1983-10-20 | Holger A.G. Dr.med. 7300 Esslingen Müller | Küvette für Kapillarblut |
US4627879A (en) * | 1984-09-07 | 1986-12-09 | The Trustees Of Columbia University In The City Of New York | Fibrin adhesive prepared as a concentrate from single donor fresh frozen plasma |
-
1987
- 1987-10-30 EP EP19870907885 patent/EP0335882A4/en not_active Withdrawn
- 1987-10-30 WO PCT/US1987/002899 patent/WO1988003045A1/fr not_active Application Discontinuation
- 1987-10-30 JP JP63500161A patent/JPH02501356A/ja active Pending
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US3481712A (en) * | 1959-11-20 | 1969-12-02 | Clay Adams Inc | Sediment container and cap and analysis technique |
US3897902A (en) * | 1974-02-01 | 1975-08-05 | Sindco Corp | Phase separating tube |
US3986506A (en) * | 1974-09-03 | 1976-10-19 | Baxter Travenol Laboratories, Inc. | Apparatus for separation of cryoprecipitate from blood plasma and method |
US4364903A (en) * | 1981-04-02 | 1982-12-21 | Becton, Dickinson And Company | Contamination-free separation device |
US4483825A (en) * | 1982-07-09 | 1984-11-20 | Fatches Keith R | Pipette and filter combination |
US4698311A (en) * | 1985-10-30 | 1987-10-06 | Ortho Diagnostic Systems Inc. | Particle washing and separation method |
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Title |
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"Now the way is clear for you to Provide Leukopoor Platelets ... with the Cutter Leukotrap Platelet Pooling System", publication of Miles Laboratories C.B. -676 (1985). See the entire document. * |
See also references of EP0335882A4 * |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0509054A4 (en) * | 1990-01-03 | 1993-07-28 | Cryolife, Inc | Preparation of fibrinogen/factor xiii precipitate |
EP0499891A1 (fr) * | 1991-02-19 | 1992-08-26 | Pall Corporation | Système de filtrage du sang |
US5891327A (en) * | 1996-07-10 | 1999-04-06 | Axygen, Inc. | Centrifuge tube with rotational position index |
WO2003008012A3 (fr) * | 2001-07-18 | 2003-04-03 | Hiberna Ag | Procede et dispositif de preparation du sang |
EP3213802A3 (fr) * | 2016-03-02 | 2017-11-22 | The Boeing Company | Systeme rotatif pour enlever du gas d'un agent d'étanchéité |
US10080981B2 (en) | 2016-03-02 | 2018-09-25 | The Boeing Company | In-line centrifugal sealant debubbler |
Also Published As
Publication number | Publication date |
---|---|
JPH02501356A (ja) | 1990-05-17 |
EP0335882A4 (en) | 1990-09-26 |
EP0335882A1 (fr) | 1989-10-11 |
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