|Publication number||WO1984001292 A1|
|Publication date||12 Apr 1984|
|Filing date||22 Aug 1983|
|Priority date||27 Sep 1982|
|Also published as||CA1227432A, CA1227432A1, EP0120875A1, EP0120875A4|
|Publication number||PCT/1983/1290, PCT/US/1983/001290, PCT/US/1983/01290, PCT/US/83/001290, PCT/US/83/01290, PCT/US1983/001290, PCT/US1983/01290, PCT/US1983001290, PCT/US198301290, PCT/US83/001290, PCT/US83/01290, PCT/US83001290, PCT/US8301290, WO 1984/001292 A1, WO 1984001292 A1, WO 1984001292A1, WO 8401292 A1, WO 8401292A1, WO-A1-1984001292, WO-A1-8401292, WO1984/001292A1, WO1984001292 A1, WO1984001292A1, WO8401292 A1, WO8401292A1|
|Inventors||Gerald A Grode|
|Applicant||Baxter Travenol Lab|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (8), Non-Patent Citations (1), Referenced by (12), Classifications (12), Legal Events (5)|
|External Links: Patentscope, Espacenet|
METHOD AND CONTAINER FOR STORING PLATELETS
The present invention relates to the storage of blood components. More particularly, the present invention relates to the storage of platelets in concentrated form.
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 cells, plasma, platelets and cryoprecipitate, for example. The individual components may then be stored for a limited period of time and then utilized as desired. For example, platelet concentrates may be used in the treatment of thrombocytopenia. Since platelets are generally stored for a period of time before use, effective storage techniques are needed.
Generally, preferred storage conditions for platelet concentrates include storage in medical grade polyvinyl chloride (PYC) bags at about 22°C. 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 PVC include epoxidized soybean oil and epoxidized linseed oil. For example, such platelet storage bags are disclosed in U.S. Patent No. 4,280,497 to Warner et al. A unit of platelet concentrate (the amount of platelet concentrate obtained from a unit of blood) whould 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 90%, 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 be 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 of 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 that the following range is satisfied: 110 ≤ R ≤ 360 wherein
FT 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
In accordance with another aspect of the invention an improved platelet storage container for maintaining a unit of plaatelets at an acceptable level of viability is provided wherein the gas transfer rate (GTR) of the container satisfies the following range: 85 ≤ GTR ≤ 180
and wherein GTR is in units of (nanomoles)/(min.-cm
and C, SA and FT are the same variables as in
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
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:
85 ≤ GRT ≤ 180
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:
110 ≤ R ≤ 360
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: 85 ≤ GTR ≤ 180 wherein
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 storage container is manufactured for containing a number or number range of platelet cells in which the following range is satisfied: 110 ≤ R ≤ 360,
Usually, the container will be constructed of a flexible polymer film material of a suitable type. Suitable types of polymers include plastlcized polyvinyl chloride compositions, polyethylene materials and polyolefin materials. BRIEF DESCRIPTION OF THE 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.
Referring to Fig. 1, there is illustrated a platelet storage container in accordance with the present invention which is a platelet storage bag 10. 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 (not shown). Also, as illustrated, the container includes a number of normally sealed, selectively operable access ports 12. 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. 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 1011 platelet cells, a container having a GTR of 165 would have an R of 110 when 1.5 x 1011 platelets are stored therein and an R of 330 when 0.5 x 1011 platelets are stored therein. If the container was optimized for a narrower range of platelet cells, such as from 0.75 x 1011 to 1.25 x 1011, an R value could be provided within the more preferred R range of 120 ≤ R ≤ 270. For example, storage of platelet celIs 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 GTR is within the desired range. Other types of materials, polymers or nonpolymers, 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 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 antiblock 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, as the amount of plasticizer 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 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 resin 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 antiblock agent will be present in an amount sufficient to provide the desired antiblock effect, or stated otherwise, to prevent adhesion of films made from the composition. The amount of antiblock 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 antiblock agent is generally the minimum amount which will prevent adhesion of films made from the composition.
An especially preferred composition is, per 100 parts of PVC resin, 74 parts of tri(2-ethylhexyl) trimellitate, 0.3 parts of a calcium stearate and zinc stearate heat stabilizer sold by the trade designation "CZ-11-P" by the Interstab
Company and about 0.4 parts of a wax antiblock agent sold under the trade designation "Acrawax C" by Glyco Chemicals, Inc. Such a composition has a
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 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 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 PVC composition without calcium stearate is more likely to undesirably darken during processing than a PVC composition containing calcium stearate and zinc stearate.
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 B.F. Goodrich Chemical Co. under the trade designation "GEON 80X80." Another preferred resin is marketed by the Wacker Co. under the trade designation "VINNOL H70DF".
The plasticizer which may be utilized, tri(2-ethylhexyl) trimellitate, is commercially available. One source is the Hatco Chemical Corp. marketing the plasticizer under the trade designation "HATCOL 200".
As previously discussed, the heat stabilization system may be calcium stearate, zinc stearate or mixtures thereof. More generally, the heat stabilization system can be at least one salt of C10 to C26 saturated fatty acids. A 1:1 weight ratio of zinc stearate/calcium stearate is preferred. A suitable coπmercial source of the zinc stearate/calcium stearate combination is the Interstab Company which markets such a heat stabilizer under the trade designation "CZ-11-P". "CZ-11-P" formulation may also contain minor amounts of calcium palmitate, zinc palmitate and C18 fatty acids. The antiblock agent which may be present generally may be any material that provides the desired antiblock effect without an undesired degree of leaching and which is not otherwise objectionable. Preferred antiblock 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 antiblock agents may also be used. Reference is made to United States Patent Application Serial No. 424,679 filed September 27, 1982 for a more complete description of such PVC compositions. Other PVC compositions may contain an epoxidized vegetable oil or oils which function as a heat stabilizer. Such compositions are disclosed in U.S. Patent No.4,280,497 to Warner et al. 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 pH of the stored platelets since it is generally recognized that pH is the best indication of eventual in vivo platelet survival and function after infusion. Generally it is desired that the pH of stored platelets remain in the pH range of from about 6.5 to about 7.2 during storage.
The following types of materials and storage bags were utilized:
Bag Volume/Surface Area: 300 ml/365 cm2 1000 ml/644 cm2
300 ml bag: 0.03 cm
1000 ml bag: 0.045 cm
Type: Polyvinyl chloride
Bag Volume/Surface Area: 300 ml/280 cm2 600 ml/398 cm2
Thickness: 300 ml bag: 0.015 cm 600 ml bag: 0.015 cm
Type: Polyvinyl chloride
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:
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 pH 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 pH instability and pH 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 pH which was generally 6.5 and 7.2. Units not stored within that GTR range generally exhibited pH values outside of the range of 6.5 to 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 alteratins as fall within the scope of the appended claims.
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|US9315775||18 Jun 2014||19 Apr 2016||Mayo Foundation For Medical Education And Research||Methods and materials for prolonging useful storage of red blood cell preparations and platelet preparations|
|US9440011||5 Jul 2013||13 Sep 2016||Terumo Bct, Inc.||Hybrid blood component storage bag and method of making such bag|
|International Classification||A61M1/00, A61J1/10, A61J1/00, A01N1/02, A61J1/05|
|Cooperative Classification||A61J1/10, A01N1/02, A01N1/0263, A61M2202/0427|
|European Classification||A01N1/02, A61J1/10, A01N1/02M4|
|12 Apr 1984||AK||Designated states|
Designated state(s): AU BR JP
|12 Apr 1984||AL||Designated countries for regional patents|
Designated state(s): BE CH DE FR GB SE
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