CA1227432A - Method and container for storing platelets - Google Patents
Method and container for storing plateletsInfo
- Publication number
- CA1227432A CA1227432A CA000436747A CA436747A CA1227432A CA 1227432 A CA1227432 A CA 1227432A CA 000436747 A CA000436747 A CA 000436747A CA 436747 A CA436747 A CA 436747A CA 1227432 A CA1227432 A CA 1227432A
- Authority
- CA
- Canada
- Prior art keywords
- container
- platelet
- gtr
- range
- platelets
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
- A61J1/10—Bag-type containers
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0236—Mechanical aspects
- A01N1/0263—Non-refrigerated containers specially adapted for transporting or storing living parts whilst preserving, e.g. cool boxes, blood bags or "straws" for cryopreservation
-
- 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
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/04—Liquids
- A61M2202/0413—Blood
- A61M2202/0427—Platelets; Thrombocytes
Abstract
ABSTRACT
Methods and containers for storing platelet cells are provided. In accordance with one aspect of the invention, an improved container for storing a unit of platelet cells at an acceptable level of viability is provided wherein the container is made of polymer material and the container meets the following requirement for the gas transmission rate: 85 ? GTR
? 180;
wherein GTR= wherein GTR is in units of (nanomoles)/(min.-cm Hgco2);
C is a unit conversion constant of 2.68 x 10-4 in units of (nanomoles-sec.)/(cc min.);
Pco2 is the CO2 gas permeability constant for the container material in units of SA is the total surface area of the container in square centimeters; and FT is the thickness of the container material in centimeters.
In accordance with the invention containers and methods are provided which optimize the storage of a particular number or number range of platelet cells, so that viability and storage time are maximized.
Methods and containers for storing platelet cells are provided. In accordance with one aspect of the invention, an improved container for storing a unit of platelet cells at an acceptable level of viability is provided wherein the container is made of polymer material and the container meets the following requirement for the gas transmission rate: 85 ? GTR
? 180;
wherein GTR= wherein GTR is in units of (nanomoles)/(min.-cm Hgco2);
C is a unit conversion constant of 2.68 x 10-4 in units of (nanomoles-sec.)/(cc min.);
Pco2 is the CO2 gas permeability constant for the container material in units of SA is the total surface area of the container in square centimeters; and FT is the thickness of the container material in centimeters.
In accordance with the invention containers and methods are provided which optimize the storage of a particular number or number range of platelet cells, so that viability and storage time are maximized.
Description
METHOD AND CONTAINER FOR STORING PLATELETS
Technical Field _ The present invention relates Jo the storage of blood components. More particularly, the present invention relates to the storage of platelets in concentrated form.
Background An_ The use of blood components instead of whole blood is now widely accepted. Blood may be collected and processed under sterile conditions to obtain various blood components as may be desired, such as packed red culls, plasma, platelets and cryoprecipitate, for example. The individual components may then be stored for a limited period of time and then utile Ed as desired. For example, platelet concentrates may be used in the Truman of thrombocytopenia. Since platelets are generally stored for a period a time before use, effective storage techniques are needed.
Generally preferred storage conditions for platelet concentrates include storage in medical grade polyvinyl chloride (PVC) bags at about 22C. Several available storage bags for platelets contain polyvinyl chloride materials which are heat stabilized with epoxidized vegetable oils. Typical epoxidized vegetable oils which are used as heat stabilizers for PUKE include epoxidized soybean oil and epoxid kid linseed oil. For example, such platelet storage bags are disclosed in US. Pun No. 4,280,497 to Warner et at. A unit of platelet concentrate (the amount of platelet concentrate obtained from a unit of blood) would have at least 0.55 x 1011 viable platelets according to the American Association of Blood Banks. Generally, a unit of platelets will contain from about 0.55 x 1011 to about 1.5 x 1011 platelet cells. Thus, the amount of platelet cells obtained from a unit of blood can vary widely. As used herein, unless otherwise specified, a unit of platelet cells contains from about 0.55 x 1011 to about 1.5 x 1011. The absolute number of platelet cells present in a unit of normal human blood can be as high as about 2.0 x 1011. Currently available platelet cell harvesting techniques generally permit harvesting about 80%, or in some cases, about 90X, of the total number of platelets present in whole blood. It is anticipated that in the future, improved harvesting techniques may become available and such improved techniques will not affect the spirit or scope of the present invention and appended claims.
The number of platelets present in a container markedly affects the storage characteristics of the platelets.
Since the number of platelets collected from a unit of blood generally varies between about 0.55 x 1011 and 1.5 x 1011, it would be highly desirable to by able to provide a container and method for storing platelets which optimize storage conditions for this particular number or number range of platelet cells or some other number or number range of platelet cells in order to maximize the storage time and viability of the stored platelet cells Disclosure of the Invention In accordance with one aspect of the present invention, it has been discovered that certain types ox storage conditions are more conducive to platelet viability over storage periods of up to at least five days. More specifically, it has been discovered that improved platelet viability results when platelet cells are stored in a container which has a carbon dioxide gas permeability transfer rate through the container within a certain range relative to the number of platelet cells stored therein. Platelet viability of the stored cells diminishes when the carbon dioxide permeability transfer rate is not within the specified range.
thus, it has been discovered that either too little or too much carbon dioxide gas transfer through the container is deleterious to the viability of stored platelets.
Generally, to optimize platelet storage and to maintain an acceptable level of platelet viability, the container should be such thaw the following range is satisfied:
wherein R = (C)x(Pco?)x(SA) (1) (FT)x(number of platelet cells to be stored in the container x 10 11) and wherein R is in units of (nanomoles C02)x(min. x owe platelet cells-cm H9CO2);
C represents a unit conversion constant of 2.S8 x 10-4 in units ox (nanomoles-sec)/(cc-min);
Pco2 represents the C02 gas permeability constant for the container material in units of banner [ (Cm3)(Cm) lo-lo]
"
(Sec)tCm')tCmHgcO2) SPA represents the total surface area of the container in square centimeters; and FIT represents the thickness of the container material in centimeters.
Preferably, the container should meet the R value requirements for any number of platelet cells between 0.55 x 1011 and 1.5 x 1011. Preferably the number of platelet cells to be stored therein will be greater than about 0.75 x loll In accordance with another aspect of the invention an improved platelet storage container for maintaining a unit of platelets at an acceptable level of viability is provided wherein the gas transfer rate (GTR) of the container satisfies the following range: 85 GTR 180 . (C)x(Pco USA (2) wherein GTR = --- 2 FIT
and wherein GTR is in units of (nanomoles)/(min.-cm H9co2) ' and C, Pro SPA and FIT are the same variables as in equation (1).
In accordance with another aspect of the invention, a method of storing platelet cells is provided and includes containing the platelet cells in a container wherein the following range is satisfied: 110 R 360 wherein R = (C)x(Pco2)x(SA) (FT)x(number of platelet cells to be stored in the container x 10~
~27~32 R, C, Pro SPA and FIT being the sap variables as in equation (1) and generally, more than about 0.75 x 10 platelet cells are stored therein.
In accordance with still another aspect of the invention, a method of storing a unit of platelet cells is provided and includes containing the unit of platelet cells in a container wherein the following range is satisfied:
wherein GTR = USA
FIT
the variables being as previously defined with respect to equations (1) and (2).
In accordance with another aspect of the invention, a container suitable for storing platelets and having a concentrate of platelet cells stored therein is provided and includes a container which satisfies the following range:
whereon R = (c)x(pco2)x(sA) (FT)x(number of platelet cells to be stored in the container x 10 11) the variables being as previously defined. Preferably, the container will have at least about 0.75 x 1011 platelet cells stored therein.
In accordance with another aspect of the invention, a container having a concentrated unit of viable platelet cells stored therein which is suitable for intravenous use is provided and includes a container which satisfies the range:
or I
I ) ) the variables being as previously defined.
In each of the foregoing embodiments, the number of platelet cells to be stored in the container can be set forth as a number range so that an optimum storage container with a specific GTR is provided for the number range of platelet cells that will be encountered. Thus, optimized containers for storing a unit of platelet cells are provided.
In accordance with still another aspect of the invention, a method is provided for manufacturing a platelet storage container of the proper size, volume and thickness for storing a given number or range of platelet cells under improved conditions so that an acceptable level of platelet viability is maintained during storage. In accordance with the method, a platelet Syria container is manufactured for containing a number or number range of platelet cells in which the hollowing range is satisfied: 110 R 360, 2Q wherein R = _ (C)xlPco2)xlSA3 Fox (number of platelet cells to be stored in the container x 10~
the variables being as previously defined. Preferably, the number of platelet cells to be stored in the container will be greater than about 0.75 x 1011.
Usually, the container will be constructed of a flexible polymer film material of a suitable type. Suitable types of polymers include plasticized polyvinyl chloride compositions, polyethylene materials and polyolefin materials.
-pa-Other important aspects of -this invention are as follows:
A platelet storage container for storing from about 1.30 x 1011 to about 3.5 x 1011 platelets at an acceptable level of viability for a period of time comprising a container constructed of material wherein the container is within the range 200 GTR 420, wherein GTR = (C)x(Pco2)x(s~) o and wherein GTR is in units of nanomoles C02/min.-Cm kiwi;
C represents the constant 2.68 x 10 nanomoles-sec./cc-min.;
Pco2 represents the C02 gas permeability constant 15 . for the material in units of banner [ (Cm3)(Cm) lo-lo]
Succumb )(CmHgc02) SPA represents the total surface area of the container in square centimeters; and FIT represents the thickness of the material in centimeters.
The platelet storage container referred to hereinabove wherein the container is for storing frock about 3.5 x 1.0 -to about 9.4 x 10 platelets and the container is within the range of 538 GTR 1130.
or I
..~, -6b-A platelet storage container for storing more than 1.30 x 1011 platelets at an acceptable level of viability for a period of time comprising a container constructed of material wherein the container is within the range, per platelet cell stored therein, of So x 10 lo TRY
3.3 x 10 9.
wherein GTR = FIT
and wherein GTR is in units of nanomoles C02/min.-cm lo H9co2;
C represents the constant 2.68 x 10-4 nanomoles-sec./cc-min.;
Pco2 represents the C02 gas permeability constant for the material in units of banner _(Cm3~(Cm) lo-lo]
Succumb )(CmHgc02) SPA represents the total surface area of the container in square centimeters; and FIT represents the thickness of the material in centimeters-I.' I
I
BRIEF DESCRIPTION OF TOE DRAWING
The present invention can be more completely understood by reference to the following Detailed Description and the accompanying drawing in which:
Fig. 1 is a plan view of a platelet storage container in accordance with the invention.
DETAILED DESCRIPTION
Referring to Fig. 1, there is illustrated a platelet storage container in accordance with the present invention which is a platelet storage bag loo Platelet storage bag 10 may be of conventional construction, with the exception of the type of materials of which it is made and the size and thickness of the container. As illustrated, platelet storage bag 10 includes an inlet port 14 to which is connected a length of flexible tubing 16 to a donor bag (not shown), for example.
Alternately, tubing 16 may communicate with the interior of another container snot Sheehan Also, as illustrated, the container includes a number of normally sealed, selectively operable access ports 12.
I As previously discussed, the container satisfies the range 110 R 360. Preferably, R is greater than 120 and even more preferably R is greater than 140. Most preferably, R is greater than 160~ Preferably, R is less than 270 and most preferably, R is less than 210. For storing a unit of platelets in accordance with the methods and containers of the invention, the gas transfer rate, ~'GTR", as previously discussed, is within the range 85 GTR 180. Preferably GTR
is within the range 100 GTR 170 and more preferably 120 GTR 170. The most preferred range for GTR for storing a unit of platelet cells is from about 160 to about 170.
I
In accordance with the invention, a platelet storage container can be provided which is optimized for storing a number of platelet cells within a given range. A container is provided such that the GTR of the container preferably provides an R value within the range of 110 R 360 and more preferably 120 R 270 for the entire range of platelet cells which may be stored in the container. For example, if an optimum platelet container is desired for storage of a unit of platelet concentrate, which generally may contain from about 0.5 x 1011 to about 1.5 x 10~1 platelet cells, a container having a GTR of 165 would have an R of 110 when 1.5 x 10 platelets are stored therein and an R of 330 when 0.5 x 1011 platelets are stored wherein. If the container was optimized for a narrower range of platelet cells, such as from 0.7~ x owe to 1.25 x 10113 an R value could be provided within the more preferred R range of 120 R 270. For example storage of platelet cells in a container having a GTR of between about 150 and 180 would always result in an R value in the range of 120 R 240 when from 0.75 x 1011 to 1.25 x 1011 platelet cells are stored therein. Thus, the invention allows platelet storage containers to be optimized for storage of a wide range of platelet cells, such as the range encountered when units of platelet concentrate are obtained from units of blood.
Platelet storage bag 10 may be constructed of a material of a suitable type. For example, polymer material such as a plasticized polyvinyl chloride resin compositions, polyethylene material and polyolefin material may be used.
Such materials may be plasticized and heat stabilized as desired by any suitable material or materials known to those skilled in the art, as long as the resulting material is suitable for storing platelets and the value of R or TRY is within the desired range. Other types of materiels, polymers or non polymers, may be used, as long as the requirements for gas transfer are provided. Thus, combinations of materials could be used and materials having various thickness could also be used, as long as the overall gas transfer requirements are met. For example, a container could have a very thick, relatively non-porous portion or portions with other portions of the container being relatively porous, as long as the overall gas transfer requirements are met. Thus, the invention is not limited to containers of a certain material or design or to materials having a uniform thickness. Polymers and polymer films are generally useful in practicing the invention.
For example, one preferred type of polyvinyl chloride composition includes PVC resin, an effective amount of it tri-(2-ethylhexyl) trimellitate to plasticize the PVC, less than about one percent by weight of the total composition of the heat stabilization system and optionally an effective amount of an anti block agent.
As will be appreciated, the amount of plasticizer can be chosen such that the desired degree of flexibility is obtained. Compositions containing a relatively low quantity of plasticizer may be harder and less flexible than desired and those with a relatively high quantity of plasticizer may be softer and more flexible than desired. Generally, do the amount of plastic ken is increased, mixing becomes more difficult and plasticizer leaching will be increased and as the amount of plasticizer decreases, gas permeability generally decreases, which may not be desirable for platelet storage.
Generally, an effective amount of plasticizer for this type of .. . . . . . . . . .. . . . . , . . , .. , ,, . , . .. . .
I
composition will be from about 25 to 90 parts per 100 parts resin by weight. Preferably, the amount of plasticizer is from about 63 to 85 parts per 100 parts rosin by weight and most preferably about 74 parts.
The heat stabilization system should generally be present in an amount greater than about 0.15 percent by weight of the total composition and is preferably present in an amount of between about 0.26 and 0.35 parts per 100 parts resin by weight. Generally, as the amount of heat stabilizer is increased, increased leaching occurs and hazing may also result if the amount of heat stabilizer is high enough.
Generally, when utilized, the anti block agent will be present in an amount sufficient to provide the desired anti block effect, or stated otherwise, to prevent adhesion of films made from the composition. The amount of anti block agent will usually be from about 0.2 to about 0.6 parts per 100 parts resin by weight and preferably about 0.4 parts. Again, generally as the amount of wax increases, increased leaching also results. Thus, the preferred amount of ankiblock agent is generally the minimum amount which will prevent adhesion of films made prom the composition.
An especially preferred composition is, per 100 parts of PVC resin, 74 parts of tri(2-ethylhexyl) trimelli~ate, 0.3 parts of a calcium Stewart and zinc Stewart heat stabilizer sold by the trade designation "SHEA P" by the Inter stab Company and about 0.4 parts of a wax anti block agent sold under the trade designation "Acrawax C" by Glyco Chemicals, Inc.
Such a composition has a Pco2 at 25C of about 49 bar.
The ingredients of a composition can generally be suitably mixed by a blender, for example. A composition can be formed into sheets by conventional methods such as by calendaring or by extrusion to a desired thickness. A mixing :~22~'~3~
screw type apparatus may be used in extruding the material.
Generally, the materials are processed under suitable conditions so that unacceptable heat degradation or color change of the material does not occur. The type and amount of 5 heat stabilizer will affect the processing conditions to which the composition may be subjected without the occurrence of significant degradation or color change. For example, a PUKE
composition without calcium Stewart is more likely to undesirably darken during processing than a PVC composition lo containing calcium Stewart and zinc Stewart.
The polyvinyl chloride resin can be any suitable type. Those types of PVC resins which relatively easily absorb the plasticizer are preferred. Especially suitable resins are those known as "blotter" resins. One such preferred resin is marketed by the BY Goodrich Chemical Co. under the trade designation "GOON 80X80." Another preferred resin is marketed by the Weaker Co. under the trade mark "YINNOL H70DF".
The plasticizer which may be utilized, trit2-ethylhexyl) trimellitate, is commercially available. One zap source is the Hatch Chemical Corp. marketing the plasticizer under the trade mark "~ATCOL 200".
As previously discussed, the heat stabile ration system may be calcium Stewart, zinc Stewart or mixtures thereof.
More generally, the heat stabilization system can be at least on salt of C10 to C26 saturated fatty acids. A 1:,1 weight ratio of zinc stearate/calcium Stewart is preferred. A
suitable commercial source of the zinc stearate/calcium Stewart combination is the Inter stab Company which markets such a heat stabilizer under the trade designation "SHOP".
"CZ-ll-P" formulation may also contain minor amounts of calcium palpitate, zinc palpitate and C18 fatty acids.
'7~3~
~12-The anti block agent which may be present generally may be any material that provides the desired anti block effect without an undesired degree of leaching and which is not otherwise objectionable. Preferred anti block agents are low viscosity, high melting point waxes, such as wax marketed under the trade designation "Acrawax C" by Glycol Chemicals, Inc.
High viscosity oils may also be utilized. In general, oils will leach to a greater degree than waxes. Mixtures of anti block agents may also be used. Reference is made to-Canadian Patent Application Serial No. 434,993 filed August 19, 1983 for a more complete description of such PVC
compositions. Other PUKE compositions may contain an epoxidized vegetable oil or oils which function as a heat stabilizer.
Such compositions are disclosed in US. Patent No. 4,280,497 to Warner et at. and reference is made thereto for further descriptions thereof. However it should be kept in mind that the scope and spirit of the present invention is not limited to particular materials or compositions.
Generally, the thickness of the polymer material will be between about 0.01 centimeter and 0.05 centimeter.
Other platelet storage materials may be used including those previously described and other which are known to those skilled in the art.
The present invention can be further understood by reference to the following example.
Example A study was conducted with various types of platelet storage bats to demonstrate the effect of "R" and "GTR" on platelet viability during storage for three and five days. The effect on platelet viability was determined by the pi of the . _ . . . .
I
stored platelets since it is generally recognized that pi is the best indication of eventual in viva platelet survival and function after infusion. Generally it is desired that the pi of stored platelets remain in the pi range of from about 6.5 to about 7.2 during storage.
The following types of materials and storage bags were utilized:
. .. . _ .. .. .. . . . . . .. .. .
Material A
Type: Polyolefin Pco2 a 25C: 58 bar Bag Yolume/Surface Area:
300 ml/365 cam 1000 ml/644 cm2 Thickness:
300 ml bag. 0.03 cm 1000 ml bag: 0.045 cm Metro at B
Type: Polyvinyl chloride Pco2 at 25~C: 4g bar Bag Volume/Surface Area:
300 ml/280 cm2 600 ml/39B cm2 Thy ckness:
300 ml bag: 0.015 cm 600 ml bag: 0.015 cm Material C
Type: Polyvinyl chloride - Pco2 at 25~C 30 bar Bag Volume/Surface Area:
300 ml/280 cm2 Thickness:
0.038 cm .
Platelet concentrate was obtained from single units of blood or from a continuous centrifugation system in which blood was continuously withdrawn, centrifuged to remove platelets and returned to the donor. The platelets were stored at ambient temperature and the following results were obtained after storage for about three and five days:
. . .
Three and Five Day Sty a # Platelet pi pi Cells Bag wafter (after Material (x10 11) Size R GTR 3 days) 5 days) C 4.66 2000ml 45 208 5.88 C 1.29 300ml 46 59 5.76 5.79 C 4.40 2000ml 47 208 5.98 C 1.24 300ml 48 59 5.67 5.67 C 4.13 2000ml 50 208 6.09 C 3.86 2000ml 54 208 5.84 A 4.13 lamely 54 223 5.92 5.75 C 1.01 300ml 59 59 5.70 5.64 A 3.62 1000ml 62 223 6.24 5.89 C 3.35 2000ml 62 208 6.11 A 3.58 1000ml 62 223 6.24 5.92 A 3.18 1000ml 70 223 6.10 6.18 C 0.76 300ml 78 59 6.08 5.62 C 0.74 300ml 80 59 5.95 5.67 B 1.15 300ml 84 97 6.19 5.63 0 0.59 300ml 100 59 6.04 5.72 B 0.86 300lnl 113 97 6.57 6.69 C 0.51 300ml 116 59 6.70 6.38 B 1.00 600ml 137 137 7.05 6.94 B 0.69 300ml 140 97 7.11 6.89 C 0.42 300ml 141 59 7.30 7.23 B 0.62 300ml 156 97 7.12 6.88 B 0.81 600ml 170 137 7.07 go A 1.00 300ml 189 189 7~10 6.96 B 0.50 300ml 193 97 7.26 6.84 B 0067 600ml 206 137 7.06 6.92 Three and Five Day Storage # Platelet pi pi Cells Bag (after (after Material (lo 11) Size R GTR 3 days) 5 days A 0.85 300ml 227 189 7.42 7.26 A 0.65 300ml 291 189 7.45 7.36 A 0.55 300ml 344 189 7.29 7.23 A 0.46 300ml 411 - 189 7.65 7.80 A 0.42 300ml 450 189 7.91 7.91 10 A 0.17 300ml 1,112 189 7.71 8.03 I
Thus, the foregoing results indicate the critical nature of the R and GTR parameters. Platelets stored under conditions such that R was with the range 110 R 360 exhibited a relatively uniform pi which was generally with the range of from 6.5 to 7.2 after 3 and 5 days of storage. Platelets stored under conditions such that R was not within the range 110 R 360 exhibited more pi instability and pi values that were generally significantly higher or lower than the range of from 6.5 to 7.2. Platelet units between about 0.5 and 1.5 x 1011 platelet cells) stored under conditions such that GTR was within the range 85 GTR 180 for 3 and 5 days also exhibited a relatively uniform pi which was generally 6.5 and 7.2. Units not stored within that GTR range generally exhibited pi values outside of the range of 6.5 Jo 7.2.
While the invention has been described with respect to preferred embodiments, it is understood that the invention is capable of changes, modifications and alterations as fall within the scope of the appended claims.
Technical Field _ The present invention relates Jo the storage of blood components. More particularly, the present invention relates to the storage of platelets in concentrated form.
Background An_ The use of blood components instead of whole blood is now widely accepted. Blood may be collected and processed under sterile conditions to obtain various blood components as may be desired, such as packed red culls, plasma, platelets and cryoprecipitate, for example. The individual components may then be stored for a limited period of time and then utile Ed as desired. For example, platelet concentrates may be used in the Truman of thrombocytopenia. Since platelets are generally stored for a period a time before use, effective storage techniques are needed.
Generally preferred storage conditions for platelet concentrates include storage in medical grade polyvinyl chloride (PVC) bags at about 22C. Several available storage bags for platelets contain polyvinyl chloride materials which are heat stabilized with epoxidized vegetable oils. Typical epoxidized vegetable oils which are used as heat stabilizers for PUKE include epoxidized soybean oil and epoxid kid linseed oil. For example, such platelet storage bags are disclosed in US. Pun No. 4,280,497 to Warner et at. A unit of platelet concentrate (the amount of platelet concentrate obtained from a unit of blood) would have at least 0.55 x 1011 viable platelets according to the American Association of Blood Banks. Generally, a unit of platelets will contain from about 0.55 x 1011 to about 1.5 x 1011 platelet cells. Thus, the amount of platelet cells obtained from a unit of blood can vary widely. As used herein, unless otherwise specified, a unit of platelet cells contains from about 0.55 x 1011 to about 1.5 x 1011. The absolute number of platelet cells present in a unit of normal human blood can be as high as about 2.0 x 1011. Currently available platelet cell harvesting techniques generally permit harvesting about 80%, or in some cases, about 90X, of the total number of platelets present in whole blood. It is anticipated that in the future, improved harvesting techniques may become available and such improved techniques will not affect the spirit or scope of the present invention and appended claims.
The number of platelets present in a container markedly affects the storage characteristics of the platelets.
Since the number of platelets collected from a unit of blood generally varies between about 0.55 x 1011 and 1.5 x 1011, it would be highly desirable to by able to provide a container and method for storing platelets which optimize storage conditions for this particular number or number range of platelet cells or some other number or number range of platelet cells in order to maximize the storage time and viability of the stored platelet cells Disclosure of the Invention In accordance with one aspect of the present invention, it has been discovered that certain types ox storage conditions are more conducive to platelet viability over storage periods of up to at least five days. More specifically, it has been discovered that improved platelet viability results when platelet cells are stored in a container which has a carbon dioxide gas permeability transfer rate through the container within a certain range relative to the number of platelet cells stored therein. Platelet viability of the stored cells diminishes when the carbon dioxide permeability transfer rate is not within the specified range.
thus, it has been discovered that either too little or too much carbon dioxide gas transfer through the container is deleterious to the viability of stored platelets.
Generally, to optimize platelet storage and to maintain an acceptable level of platelet viability, the container should be such thaw the following range is satisfied:
wherein R = (C)x(Pco?)x(SA) (1) (FT)x(number of platelet cells to be stored in the container x 10 11) and wherein R is in units of (nanomoles C02)x(min. x owe platelet cells-cm H9CO2);
C represents a unit conversion constant of 2.S8 x 10-4 in units ox (nanomoles-sec)/(cc-min);
Pco2 represents the C02 gas permeability constant for the container material in units of banner [ (Cm3)(Cm) lo-lo]
"
(Sec)tCm')tCmHgcO2) SPA represents the total surface area of the container in square centimeters; and FIT represents the thickness of the container material in centimeters.
Preferably, the container should meet the R value requirements for any number of platelet cells between 0.55 x 1011 and 1.5 x 1011. Preferably the number of platelet cells to be stored therein will be greater than about 0.75 x loll In accordance with another aspect of the invention an improved platelet storage container for maintaining a unit of platelets at an acceptable level of viability is provided wherein the gas transfer rate (GTR) of the container satisfies the following range: 85 GTR 180 . (C)x(Pco USA (2) wherein GTR = --- 2 FIT
and wherein GTR is in units of (nanomoles)/(min.-cm H9co2) ' and C, Pro SPA and FIT are the same variables as in equation (1).
In accordance with another aspect of the invention, a method of storing platelet cells is provided and includes containing the platelet cells in a container wherein the following range is satisfied: 110 R 360 wherein R = (C)x(Pco2)x(SA) (FT)x(number of platelet cells to be stored in the container x 10~
~27~32 R, C, Pro SPA and FIT being the sap variables as in equation (1) and generally, more than about 0.75 x 10 platelet cells are stored therein.
In accordance with still another aspect of the invention, a method of storing a unit of platelet cells is provided and includes containing the unit of platelet cells in a container wherein the following range is satisfied:
wherein GTR = USA
FIT
the variables being as previously defined with respect to equations (1) and (2).
In accordance with another aspect of the invention, a container suitable for storing platelets and having a concentrate of platelet cells stored therein is provided and includes a container which satisfies the following range:
whereon R = (c)x(pco2)x(sA) (FT)x(number of platelet cells to be stored in the container x 10 11) the variables being as previously defined. Preferably, the container will have at least about 0.75 x 1011 platelet cells stored therein.
In accordance with another aspect of the invention, a container having a concentrated unit of viable platelet cells stored therein which is suitable for intravenous use is provided and includes a container which satisfies the range:
or I
I ) ) the variables being as previously defined.
In each of the foregoing embodiments, the number of platelet cells to be stored in the container can be set forth as a number range so that an optimum storage container with a specific GTR is provided for the number range of platelet cells that will be encountered. Thus, optimized containers for storing a unit of platelet cells are provided.
In accordance with still another aspect of the invention, a method is provided for manufacturing a platelet storage container of the proper size, volume and thickness for storing a given number or range of platelet cells under improved conditions so that an acceptable level of platelet viability is maintained during storage. In accordance with the method, a platelet Syria container is manufactured for containing a number or number range of platelet cells in which the hollowing range is satisfied: 110 R 360, 2Q wherein R = _ (C)xlPco2)xlSA3 Fox (number of platelet cells to be stored in the container x 10~
the variables being as previously defined. Preferably, the number of platelet cells to be stored in the container will be greater than about 0.75 x 1011.
Usually, the container will be constructed of a flexible polymer film material of a suitable type. Suitable types of polymers include plasticized polyvinyl chloride compositions, polyethylene materials and polyolefin materials.
-pa-Other important aspects of -this invention are as follows:
A platelet storage container for storing from about 1.30 x 1011 to about 3.5 x 1011 platelets at an acceptable level of viability for a period of time comprising a container constructed of material wherein the container is within the range 200 GTR 420, wherein GTR = (C)x(Pco2)x(s~) o and wherein GTR is in units of nanomoles C02/min.-Cm kiwi;
C represents the constant 2.68 x 10 nanomoles-sec./cc-min.;
Pco2 represents the C02 gas permeability constant 15 . for the material in units of banner [ (Cm3)(Cm) lo-lo]
Succumb )(CmHgc02) SPA represents the total surface area of the container in square centimeters; and FIT represents the thickness of the material in centimeters.
The platelet storage container referred to hereinabove wherein the container is for storing frock about 3.5 x 1.0 -to about 9.4 x 10 platelets and the container is within the range of 538 GTR 1130.
or I
..~, -6b-A platelet storage container for storing more than 1.30 x 1011 platelets at an acceptable level of viability for a period of time comprising a container constructed of material wherein the container is within the range, per platelet cell stored therein, of So x 10 lo TRY
3.3 x 10 9.
wherein GTR = FIT
and wherein GTR is in units of nanomoles C02/min.-cm lo H9co2;
C represents the constant 2.68 x 10-4 nanomoles-sec./cc-min.;
Pco2 represents the C02 gas permeability constant for the material in units of banner _(Cm3~(Cm) lo-lo]
Succumb )(CmHgc02) SPA represents the total surface area of the container in square centimeters; and FIT represents the thickness of the material in centimeters-I.' I
I
BRIEF DESCRIPTION OF TOE DRAWING
The present invention can be more completely understood by reference to the following Detailed Description and the accompanying drawing in which:
Fig. 1 is a plan view of a platelet storage container in accordance with the invention.
DETAILED DESCRIPTION
Referring to Fig. 1, there is illustrated a platelet storage container in accordance with the present invention which is a platelet storage bag loo Platelet storage bag 10 may be of conventional construction, with the exception of the type of materials of which it is made and the size and thickness of the container. As illustrated, platelet storage bag 10 includes an inlet port 14 to which is connected a length of flexible tubing 16 to a donor bag (not shown), for example.
Alternately, tubing 16 may communicate with the interior of another container snot Sheehan Also, as illustrated, the container includes a number of normally sealed, selectively operable access ports 12.
I As previously discussed, the container satisfies the range 110 R 360. Preferably, R is greater than 120 and even more preferably R is greater than 140. Most preferably, R is greater than 160~ Preferably, R is less than 270 and most preferably, R is less than 210. For storing a unit of platelets in accordance with the methods and containers of the invention, the gas transfer rate, ~'GTR", as previously discussed, is within the range 85 GTR 180. Preferably GTR
is within the range 100 GTR 170 and more preferably 120 GTR 170. The most preferred range for GTR for storing a unit of platelet cells is from about 160 to about 170.
I
In accordance with the invention, a platelet storage container can be provided which is optimized for storing a number of platelet cells within a given range. A container is provided such that the GTR of the container preferably provides an R value within the range of 110 R 360 and more preferably 120 R 270 for the entire range of platelet cells which may be stored in the container. For example, if an optimum platelet container is desired for storage of a unit of platelet concentrate, which generally may contain from about 0.5 x 1011 to about 1.5 x 10~1 platelet cells, a container having a GTR of 165 would have an R of 110 when 1.5 x 10 platelets are stored therein and an R of 330 when 0.5 x 1011 platelets are stored wherein. If the container was optimized for a narrower range of platelet cells, such as from 0.7~ x owe to 1.25 x 10113 an R value could be provided within the more preferred R range of 120 R 270. For example storage of platelet cells in a container having a GTR of between about 150 and 180 would always result in an R value in the range of 120 R 240 when from 0.75 x 1011 to 1.25 x 1011 platelet cells are stored therein. Thus, the invention allows platelet storage containers to be optimized for storage of a wide range of platelet cells, such as the range encountered when units of platelet concentrate are obtained from units of blood.
Platelet storage bag 10 may be constructed of a material of a suitable type. For example, polymer material such as a plasticized polyvinyl chloride resin compositions, polyethylene material and polyolefin material may be used.
Such materials may be plasticized and heat stabilized as desired by any suitable material or materials known to those skilled in the art, as long as the resulting material is suitable for storing platelets and the value of R or TRY is within the desired range. Other types of materiels, polymers or non polymers, may be used, as long as the requirements for gas transfer are provided. Thus, combinations of materials could be used and materials having various thickness could also be used, as long as the overall gas transfer requirements are met. For example, a container could have a very thick, relatively non-porous portion or portions with other portions of the container being relatively porous, as long as the overall gas transfer requirements are met. Thus, the invention is not limited to containers of a certain material or design or to materials having a uniform thickness. Polymers and polymer films are generally useful in practicing the invention.
For example, one preferred type of polyvinyl chloride composition includes PVC resin, an effective amount of it tri-(2-ethylhexyl) trimellitate to plasticize the PVC, less than about one percent by weight of the total composition of the heat stabilization system and optionally an effective amount of an anti block agent.
As will be appreciated, the amount of plasticizer can be chosen such that the desired degree of flexibility is obtained. Compositions containing a relatively low quantity of plasticizer may be harder and less flexible than desired and those with a relatively high quantity of plasticizer may be softer and more flexible than desired. Generally, do the amount of plastic ken is increased, mixing becomes more difficult and plasticizer leaching will be increased and as the amount of plasticizer decreases, gas permeability generally decreases, which may not be desirable for platelet storage.
Generally, an effective amount of plasticizer for this type of .. . . . . . . . . .. . . . . , . . , .. , ,, . , . .. . .
I
composition will be from about 25 to 90 parts per 100 parts resin by weight. Preferably, the amount of plasticizer is from about 63 to 85 parts per 100 parts rosin by weight and most preferably about 74 parts.
The heat stabilization system should generally be present in an amount greater than about 0.15 percent by weight of the total composition and is preferably present in an amount of between about 0.26 and 0.35 parts per 100 parts resin by weight. Generally, as the amount of heat stabilizer is increased, increased leaching occurs and hazing may also result if the amount of heat stabilizer is high enough.
Generally, when utilized, the anti block agent will be present in an amount sufficient to provide the desired anti block effect, or stated otherwise, to prevent adhesion of films made from the composition. The amount of anti block agent will usually be from about 0.2 to about 0.6 parts per 100 parts resin by weight and preferably about 0.4 parts. Again, generally as the amount of wax increases, increased leaching also results. Thus, the preferred amount of ankiblock agent is generally the minimum amount which will prevent adhesion of films made prom the composition.
An especially preferred composition is, per 100 parts of PVC resin, 74 parts of tri(2-ethylhexyl) trimelli~ate, 0.3 parts of a calcium Stewart and zinc Stewart heat stabilizer sold by the trade designation "SHEA P" by the Inter stab Company and about 0.4 parts of a wax anti block agent sold under the trade designation "Acrawax C" by Glyco Chemicals, Inc.
Such a composition has a Pco2 at 25C of about 49 bar.
The ingredients of a composition can generally be suitably mixed by a blender, for example. A composition can be formed into sheets by conventional methods such as by calendaring or by extrusion to a desired thickness. A mixing :~22~'~3~
screw type apparatus may be used in extruding the material.
Generally, the materials are processed under suitable conditions so that unacceptable heat degradation or color change of the material does not occur. The type and amount of 5 heat stabilizer will affect the processing conditions to which the composition may be subjected without the occurrence of significant degradation or color change. For example, a PUKE
composition without calcium Stewart is more likely to undesirably darken during processing than a PVC composition lo containing calcium Stewart and zinc Stewart.
The polyvinyl chloride resin can be any suitable type. Those types of PVC resins which relatively easily absorb the plasticizer are preferred. Especially suitable resins are those known as "blotter" resins. One such preferred resin is marketed by the BY Goodrich Chemical Co. under the trade designation "GOON 80X80." Another preferred resin is marketed by the Weaker Co. under the trade mark "YINNOL H70DF".
The plasticizer which may be utilized, trit2-ethylhexyl) trimellitate, is commercially available. One zap source is the Hatch Chemical Corp. marketing the plasticizer under the trade mark "~ATCOL 200".
As previously discussed, the heat stabile ration system may be calcium Stewart, zinc Stewart or mixtures thereof.
More generally, the heat stabilization system can be at least on salt of C10 to C26 saturated fatty acids. A 1:,1 weight ratio of zinc stearate/calcium Stewart is preferred. A
suitable commercial source of the zinc stearate/calcium Stewart combination is the Inter stab Company which markets such a heat stabilizer under the trade designation "SHOP".
"CZ-ll-P" formulation may also contain minor amounts of calcium palpitate, zinc palpitate and C18 fatty acids.
'7~3~
~12-The anti block agent which may be present generally may be any material that provides the desired anti block effect without an undesired degree of leaching and which is not otherwise objectionable. Preferred anti block agents are low viscosity, high melting point waxes, such as wax marketed under the trade designation "Acrawax C" by Glycol Chemicals, Inc.
High viscosity oils may also be utilized. In general, oils will leach to a greater degree than waxes. Mixtures of anti block agents may also be used. Reference is made to-Canadian Patent Application Serial No. 434,993 filed August 19, 1983 for a more complete description of such PVC
compositions. Other PUKE compositions may contain an epoxidized vegetable oil or oils which function as a heat stabilizer.
Such compositions are disclosed in US. Patent No. 4,280,497 to Warner et at. and reference is made thereto for further descriptions thereof. However it should be kept in mind that the scope and spirit of the present invention is not limited to particular materials or compositions.
Generally, the thickness of the polymer material will be between about 0.01 centimeter and 0.05 centimeter.
Other platelet storage materials may be used including those previously described and other which are known to those skilled in the art.
The present invention can be further understood by reference to the following example.
Example A study was conducted with various types of platelet storage bats to demonstrate the effect of "R" and "GTR" on platelet viability during storage for three and five days. The effect on platelet viability was determined by the pi of the . _ . . . .
I
stored platelets since it is generally recognized that pi is the best indication of eventual in viva platelet survival and function after infusion. Generally it is desired that the pi of stored platelets remain in the pi range of from about 6.5 to about 7.2 during storage.
The following types of materials and storage bags were utilized:
. .. . _ .. .. .. . . . . . .. .. .
Material A
Type: Polyolefin Pco2 a 25C: 58 bar Bag Yolume/Surface Area:
300 ml/365 cam 1000 ml/644 cm2 Thickness:
300 ml bag. 0.03 cm 1000 ml bag: 0.045 cm Metro at B
Type: Polyvinyl chloride Pco2 at 25~C: 4g bar Bag Volume/Surface Area:
300 ml/280 cm2 600 ml/39B cm2 Thy ckness:
300 ml bag: 0.015 cm 600 ml bag: 0.015 cm Material C
Type: Polyvinyl chloride - Pco2 at 25~C 30 bar Bag Volume/Surface Area:
300 ml/280 cm2 Thickness:
0.038 cm .
Platelet concentrate was obtained from single units of blood or from a continuous centrifugation system in which blood was continuously withdrawn, centrifuged to remove platelets and returned to the donor. The platelets were stored at ambient temperature and the following results were obtained after storage for about three and five days:
. . .
Three and Five Day Sty a # Platelet pi pi Cells Bag wafter (after Material (x10 11) Size R GTR 3 days) 5 days) C 4.66 2000ml 45 208 5.88 C 1.29 300ml 46 59 5.76 5.79 C 4.40 2000ml 47 208 5.98 C 1.24 300ml 48 59 5.67 5.67 C 4.13 2000ml 50 208 6.09 C 3.86 2000ml 54 208 5.84 A 4.13 lamely 54 223 5.92 5.75 C 1.01 300ml 59 59 5.70 5.64 A 3.62 1000ml 62 223 6.24 5.89 C 3.35 2000ml 62 208 6.11 A 3.58 1000ml 62 223 6.24 5.92 A 3.18 1000ml 70 223 6.10 6.18 C 0.76 300ml 78 59 6.08 5.62 C 0.74 300ml 80 59 5.95 5.67 B 1.15 300ml 84 97 6.19 5.63 0 0.59 300ml 100 59 6.04 5.72 B 0.86 300lnl 113 97 6.57 6.69 C 0.51 300ml 116 59 6.70 6.38 B 1.00 600ml 137 137 7.05 6.94 B 0.69 300ml 140 97 7.11 6.89 C 0.42 300ml 141 59 7.30 7.23 B 0.62 300ml 156 97 7.12 6.88 B 0.81 600ml 170 137 7.07 go A 1.00 300ml 189 189 7~10 6.96 B 0.50 300ml 193 97 7.26 6.84 B 0067 600ml 206 137 7.06 6.92 Three and Five Day Storage # Platelet pi pi Cells Bag (after (after Material (lo 11) Size R GTR 3 days) 5 days A 0.85 300ml 227 189 7.42 7.26 A 0.65 300ml 291 189 7.45 7.36 A 0.55 300ml 344 189 7.29 7.23 A 0.46 300ml 411 - 189 7.65 7.80 A 0.42 300ml 450 189 7.91 7.91 10 A 0.17 300ml 1,112 189 7.71 8.03 I
Thus, the foregoing results indicate the critical nature of the R and GTR parameters. Platelets stored under conditions such that R was with the range 110 R 360 exhibited a relatively uniform pi which was generally with the range of from 6.5 to 7.2 after 3 and 5 days of storage. Platelets stored under conditions such that R was not within the range 110 R 360 exhibited more pi instability and pi values that were generally significantly higher or lower than the range of from 6.5 to 7.2. Platelet units between about 0.5 and 1.5 x 1011 platelet cells) stored under conditions such that GTR was within the range 85 GTR 180 for 3 and 5 days also exhibited a relatively uniform pi which was generally 6.5 and 7.2. Units not stored within that GTR range generally exhibited pi values outside of the range of 6.5 Jo 7.2.
While the invention has been described with respect to preferred embodiments, it is understood that the invention is capable of changes, modifications and alterations as fall within the scope of the appended claims.
Claims (3)
1. A platelet storage container for storing from about 1.30 x 1011 to about 3.5 x 1011 platelets at an acceptable level of viability for a period of time comprising a container constructed of material wherein the container is within the range 200 ? GTR ? 420, wherein GTR = and wherein GTR is in units of nanomoles CO2/min.-cm Hgco2;
C represents the constant 2.68 x 10-4 nanomoles-sec./cc-min.;
Pco2 represents the CO2 gas permeability constant for the material in units of SA represents the total surface area of the container .
in square centimeters; and FT represents the thickness of the material in centimeters.
C represents the constant 2.68 x 10-4 nanomoles-sec./cc-min.;
Pco2 represents the CO2 gas permeability constant for the material in units of SA represents the total surface area of the container .
in square centimeters; and FT represents the thickness of the material in centimeters.
2. The platelet storage container of claim l wherein the container is for storing from about 3.5 x 1011 to about 9.4 x 1011 platelets and the container is within the range of 538 ? GTR ? 1130.
3. A platelet storage container for storing more than 1.30 x 1011 platelets at an acceptable level of viability for a period of time comprising a container constructed of material wherein the container is within the range, per platelet cell stored therein, of 8.5 x 10-10 ? GTR
? 3.3 x 10-9.
wherein GTR = and wherein GTR is in units of nanomoles CO2/min.-cm Hgco2;
C represents the constant 2.68 x 10-4 nanomoles-sec./cc-min.;
Pco2 represents the CO2 gas permeability constant for the material in units of SA represents the total surface area of the container in square centimeters; and FT represents the thickness of the material in centimeters.
? 3.3 x 10-9.
wherein GTR = and wherein GTR is in units of nanomoles CO2/min.-cm Hgco2;
C represents the constant 2.68 x 10-4 nanomoles-sec./cc-min.;
Pco2 represents the CO2 gas permeability constant for the material in units of SA represents the total surface area of the container in square centimeters; and FT represents the thickness of the material in centimeters.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US42467882A | 1982-09-27 | 1982-09-27 | |
| US424,678 | 1982-09-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1227432A true CA1227432A (en) | 1987-09-29 |
Family
ID=23683483
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000436747A Expired CA1227432A (en) | 1982-09-27 | 1983-09-15 | Method and container for storing platelets |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0120875A4 (en) |
| JP (1) | JPS59501733A (en) |
| CA (1) | CA1227432A (en) |
| WO (1) | WO1984001292A1 (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8427285D0 (en) * | 1984-10-29 | 1984-12-05 | Bellhouse Medical Products Ltd | Blood bag |
| JPH0435670A (en) * | 1990-05-31 | 1992-02-06 | Nissho Corp | Blood separating device |
| US5683768A (en) * | 1994-12-21 | 1997-11-04 | Baxter International Inc. | Plastic formulations for platelet storage containers and the like |
| EP1689228A2 (en) | 2003-10-22 | 2006-08-16 | Fred Hutchinson Cancer Research Center | Methods, compositions and devices for inducing stasis in cells |
| DE602008005349D1 (en) | 2008-12-29 | 2011-04-14 | Fiat Ricerche | Fuel injection system with high repeatability and stability for an internal combustion engine |
| CN103702557A (en) * | 2011-03-16 | 2014-04-02 | 梅奥医学教育和研究基金会 | Methods and materials for prolonging useful storage of red blood cell preparations and platelet preparations |
| WO2014011499A1 (en) | 2012-07-12 | 2014-01-16 | Terumo Bct, Inc. | Hybrid blood component storage bag and method of making such bag |
| CN114600872A (en) * | 2022-04-13 | 2022-06-10 | 西安北光医学生物技术有限公司 | Method and system for anti-damage preservation of cells, tissues or organs |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3928294A (en) * | 1972-02-22 | 1975-12-23 | Owens Illinois Inc | Biocompatible articles including polymeric membranes having high permeability to gases and uses thereof |
| US4132594A (en) * | 1976-06-28 | 1979-01-02 | The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration | Gas diffusion liquid storage bag and method of use for storing blood |
| US4082509A (en) * | 1976-08-05 | 1978-04-04 | Dow Corning Corporation | Method of storing blood and a blood storage bag therefor |
| AU489541B2 (en) * | 1976-08-24 | 1978-01-19 | Green Cross Corporation, The | Medical appliance made of plastic |
| JPS5841862B2 (en) * | 1977-01-08 | 1983-09-14 | テルモ株式会社 | medical equipment |
| US4228032A (en) * | 1978-11-06 | 1980-10-14 | Dow Corning Corporation | Method of storing blood and a blood storage bag therefore |
| JPS5676955A (en) * | 1979-11-27 | 1981-06-24 | Sekisui Chemical Co Ltd | Manufacture of medical resin molding |
| US4496361A (en) * | 1981-08-05 | 1985-01-29 | E. I. Du Pont De Nemours And Company | Platelet storage container |
-
1983
- 1983-08-22 WO PCT/US1983/001290 patent/WO1984001292A1/en not_active Application Discontinuation
- 1983-08-22 EP EP19830902868 patent/EP0120875A4/en active Pending
- 1983-08-22 JP JP50291883A patent/JPS59501733A/en active Pending
- 1983-09-15 CA CA000436747A patent/CA1227432A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| EP0120875A1 (en) | 1984-10-10 |
| JPS59501733A (en) | 1984-10-18 |
| WO1984001292A1 (en) | 1984-04-12 |
| EP0120875A4 (en) | 1985-12-05 |
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