JPH03218770A - Bag for preserving platelet and composite bag formed by using this bag - Google Patents

Abstract

PURPOSE:To lessen the bleeding out of a plasticizer to a thick liquid of the platelet and to obviate the degradation in the function of the platelet by adding a specific ratio of the plasticizer to a specific polymer alloy. CONSTITUTION:This bag is a polymer mixture consisting of the compsn. comprising 25 to 60wt.% poly(ethylene butyrene) polystyrene block copolymer, 20 to 40wt.% polypropylene, and 5 to 35wt.% ethylene acrylate ester copolymer. This block copolymer has at least >=2 pieces of the parts where the polystyrene segments are crystallized and arranged. The bag consists of the resin formed by mixing 1 to 20wt.% trimellitic acid tri-n-octyl ester, tri-2-ethyl hexyl trimellitate or the mixture composed thereof with the polymer alloy in which the molecular chains of such polymer entangle with each other like network.

Description

[Detailed Description of the Invention] [Field of Industrial Application] The present invention relates to a platelet storage bag and a composite bag using the same. This invention relates to a platelet storage bag that can be stored for a long time without deforming even during separation operations, and a composite bag using the same. [Prior art] Conventionally, a bag material for platelet storage was developed in which the collected platelets were safely stored for a long period of time and supplied when needed.
19461, a polymer composition in which poly(ethylene butylene) polystyrene block copolymer is mixed with polypropylene and ethylene vinyl acetate copolymer (or polyethylene) is introduced as a plasticizer-free resin. JP-A-55-60464 discloses that this resin is used as a child bag in a composite bag system in which blood collected from a donor is stored in a parent bag, plasma components are separated, and platelets are stored in a child bag. is introduced in.

Since the platelet bag used as this child bag does not contain a desiccant agent, the drawback of additive substances leaching into the platelets has been resolved, but the bag has a low elastic modulus at high temperatures and becomes soft during high-pressure steam sterilization. It was deformed. In particular, bags containing ethylene vinyl acetate copolymer mixed into a polymer mixture generate acetic acid due to thermal decomposition during molding and hydrolysis during high-pressure steam sterilization, and acetic acid is released and mixed into the platelet concentrate. It had the disadvantage of being acidic.

One of the inventors of the present invention developed a polymer alloy in which an ethylene acrylate copolymer is mixed with a polymer mixture of poly(ethylene butylene) polystyrene block copolymer and polypropylene as a resin that improves the drawbacks of this polymer composition. By using this as a bag for platelet storage, there is no leaching of chemicals into the platelets, there is little deformation at high or low temperatures, and there is good gas permeability.
We have already applied for a patent after discovering that a bag that can store platelets for a long period of time can be obtained.

[Problem to be solved by the invention]

However, when plasma separated from blood is stored in a bag made of this polymer alloy and platelets are separated by strong centrifugation, the bag partially bends, wrinkles occur, and blood remains, which causes the bag to become stiffer. There was a drawback that caused a decline. [Means for Solving the Problems] As a result of various studies to improve these drawbacks, the present inventors have found that by adding a specific amount of a specific plasticity law to this polymer alloy, it is possible to improve the plasticity of the platelet concentrate. The present invention was achieved by discovering that the exudation of the agent is small and does not cause a decline in platelet function. That is, the present invention comprises (a) poly(ethylene butylene) polystyrene block copolymer 25 to 60% by weight (b) polypropylene
(c) ethylene acrylic acid ester copolymer 5-35% by weight; Tri-n-octyl trimellitic acid ester, tri-n-octyl trimellitic acid, tri-
This platelet storage bag is made of a resin containing 1 to 20% by weight of 2-ethylhexyl trimellitate or a mixture thereof.

Further, the present invention provides a parent bag for storing donor blood and separating blood components, a child bag for storing the separated blood components, and a communication between the parent bag and the child bag for transporting the separated blood components. In a composite bag consisting of tubes,
This is a composite bag that uses the platelet storage bag described above as a child bag. [Function] The present invention provides a mixture of poly(ethylene butylene) polystyrene block copolymer and polypropylene at a specific blending ratio,
By adding the ethylene acrylic ester copolymer, the ethylene acrylic ester copolymer acts as a compatibilizer for the poly(ethylene butylene) polystyrene block copolymer and polypropylene to form a polymer alloy. When a bag formed using a resin in which a specific amount of a specific plasticizer is added to this polymer alloy is used for platelet storage, the polymer alloy and plasticizer are mixed uniformly, and the plasticity does not ooze out from the inner surface of the bag. Few《
, ideal for platelet storage. [Example] The poly(ethylene butylene) polystyrene block copolymer used in the present invention has a structure in which the hard segment is a styrene polymer such as polystyrene or polymethylstyrene, and the soft segment is a polyethylene butylene copolymer. There is. The molecular weight of the polystyrene polymer used as the hard segment is 5,000 to 120,000. Polyethylene butylene copolymer, which is a soft segment, is produced by reacting polybutadiene with a molecular weight of 10,000 to 250,000 with polystyrene to produce a poly(ethylene butylene) polystyrene block copolymer, and then hydrogenating the block copolymer. You can get it by doing The soft segment polyethylene butylene copolymer has a composition ratio of ethylene and butylene of 4.
0 to 60/60 to 40 mol%, and the proportion of the soft segment in the block copolymer is 60 to 90% by weight.
If this is the case, excellent mechanical properties and flexibility can be obtained. The amount of block copolymer used ranges from 2 to 2 in the polymer mixture.
If the amount used is less than 25% by weight, the flexibility of the bag tends to deteriorate;
If it exceeds 0% by weight, moldability tends to deteriorate.

Next, the polypropylene used in the present invention is polypropylene alone or a copolymer mainly composed of polypropylene. Copolymer components other than propylene include ethylene, butene-1, etc., and the proportion thereof is 10% by weight or less. Polypropylene has the ability to improve the strength when molded into bags, and by mixing it with other polymers in a specific ratio to form a polymer alloy, the strength of the resulting bag can be significantly improved. The amount of such polypropylene used ranges from 20 to 40% by weight in the polymer mixture; less than 20% by weight tends to deteriorate the transparency and strength of the bag, and more than 40% by weight tends to reduce flexibility. It tends to get worse. Next, the ethylene acrylic ester copolymer used in the present invention acts as a compatibilizer for the block copolymer and polypropylene and contributes to the formation of a polymer alloy. , ethyl acrylate, butyl acrylate, etc., and the proportion thereof in the copolymer component is 5 to 90 mol%.
It is. When the amount of acrylic acid ester is less than 5 mol%, transparency tends to deteriorate, and when it exceeds 90 mol%, the elastic modulus in a high temperature region tends to decrease. The amount of the ethylene acrylic ester copolymer used ranges from 5 to 35% by weight in the polymer mixture;
If it is less than 35% by weight, polymer dispersion will be poor, extrusion processability and transparency will be poor, and especially low temperature properties will tend to be poor, and if it exceeds 35% by weight, mechanical strength will tend to be low. When the homogeneously mixed polymer mixture is melt-extruded and molded, two or more polystyrene segments, which are hard segments of the block copolymer, are gathered together to form a crystallized and aligned region, and this region is formed by at least a portion of the polymer mixture. A chemical in which the soft segment of the block copolymer, the hard segment of the block copolymer that is not crystallized, and the molecular chains of polypropylene and ethylene acrylate copolymer are entangled with each other in a network. Forms a structured polymer alloy. The polymer mixture has a polymer alloy structure that increases mechanical strength and
It has desirable properties as a platelet storage bag, such as good mechanical properties especially at low temperatures and good gas permeability such as oxygen permeability and carbon dioxide permeability. Plasticizers added to the polymer alloy include trimellitic acid tri101 octyl ester, tri-2-ethylhexyl trimellitate, or mixtures thereof. These plasticizers can be mixed uniformly with the polymer alloy.

The amount of plasticizer added is 1 to 20% by weight, preferably 2 to 10% by weight, based on the polymer alloy. If the amount of plasticizer added is less than 1% by weight, the bag tends to bend when plasma is subjected to high-speed centrifugation to separate platelets;
If it exceeds 100%, the plasticizer leached from the bag tends to reduce platelet function.

The bag is formed by uniformly mixing the polymer alloy with a plasticizer in a blender or mixer, then melting the mixture, melt extruding it into a mold shaped like a medical bag, blow molding it, or extruding it into a sheet. Afterwards, the ends are heat-sealed to produce a medical bag. The thickness of the sheet can be selected as appropriate depending on its use; for example, the thickness of the sheet is 2.
00~450μ. Next, an example in which the platelet storage bag of the present invention is used as a child bag of a composite bag will be explained based on FIG. 1.

FIG. 1 is a schematic explanatory diagram of a composite bag, in which 1 is a blood donor, 2, 4, 6, 8, and 10 are tubes, 3 is a parent bag, 5 is a first child bag, 7 is a switching valve, 9 indicates the second child bag. The blood collected from the blood donor 1 is stored in the parent bag 3,
It is separated into blood cell components and plasma components using a centrifuge. The material for the parent bag 3 is preferably a plastic containing a plasticizer, such as polyvinyl chloride, polyolefin, the above-mentioned polymer alloy, etc. In particular, a resin in which a plasticizer is added to the above-mentioned polymer alloy is preferable because it causes less hemolysis of red blood cells. The content of plasticizer in the polymer in the material used as the parent bag can be appropriately selected depending on the type of plasticizer and the combination with the polymer, but is used, for example, from 1 to 50% by weight. The plasma components separated in the parent bag 3 pass through the tube 4,
Transfer from the tube 6 to the first child bag 5. Such tubes are made of materials such as polyvinyl chloride and polyolefin. Further, the first child bag 5 is made of the above-mentioned material. Furthermore, the first child bag 5 is subjected to high centrifugation using a centrifuge to separate platelets and other plasma components, and the plasma components other than platelets are transferred from the tube 6 to the tube 8 to the second child bag 9. ．． And platelets are the first
It is stored and stored in the child bag 5. Examples of the material for the second child bag 9 include the aforementioned plasticizer-containing polymer alloy, dioctyl phthalate-containing polyvinyl chloride, 2-ethylhexyl trimellitate-containing polyvinyl chloride, and the like. Second
Plasma components other than platelets contained in the child bag 9 are normally stored frozen.

Next, the platelet storage bag of the present invention will be explained in detail based on Examples and Comparative Examples, but the present invention is not limited to these Examples. Examples 1 to 4 Poly(ethylene butylene) polystyrene blotter copolymer (Krayton G-165040% by Shell Chemical Co., Ltd., polypropylene (PL-6711N manufactured by Sumitomo Chemical Co., Ltd.)
) 30% by weight, ethylene ethyl acrylate copolymer (
Ethyl acrylate amount: 15 mol%, Nippon Unica Co., Ltd. Kano DJ6182) 30% by weight were mixed in a mixer,
Tri-2-ethylhexyl trimellitate (TO
A sheet with a thickness of 250 μm was produced by mixing the mixture (referred to as Ding M) in the proportions shown in Table 1 and extruding it into a sheet. This sheet was placed in a bag mold, and the sheet was thermally fused and made into a bag shape. Next, the two bag-shaped sheets are overlapped and the three edges around the bag are heat welded to form a bag. Thereafter, the tube, mixed spout, and TP case were welded to the end of the bag, one of which was open, to produce a bag with an attachment capacity of 150 d.

200 m of whole blood from healthy subjects was collected in a triple bag parent bag (diothylphthalate 35
The blood was collected into a bag made of polyvinyl chloride (polyvinyl chloride bag added with 5% by weight), centrifuged at a rotational speed of 2000 rpm, and separated into blood cell components and plasma components. Then, the first child bag containing the plasma components was subjected to strong centrifugation at a rotation speed of 380 rpm to separate the platelets, and the plasma components other than the platelets were transferred to the second child bag 9 (same resin as the first child bag). A bag consisting of At this time, the platelets remaining in the first child bag were used as one unit of platelet preparation. Next, 6 units of the same type of platelet preparation were pooled in a bag with a capacity of 1.02 made of the polymer alloy, and then dispensed into the 6 types of bags obtained in this example in 20 d portions, and stored with shaking at 22° C. and 5 Q rpm. After 72 hours, platelet aggregation ability and bag deformation were tested. The measurement method in the table is as follows.

■Platelet aggregation ability This is the maximum aggregation rate induced by adding 4mM of CaClg and then adding 20μM of ADP. ■ Deformed state of the bag When the first child bag containing plasma components was subjected to strong centrifugation, the surface condition of the first child bag was classified as follows. (+) No change in surface condition ○ (2) Convex horizontal stripes occur at the bottom of the bag Δ (3) Circular convex portions occur at the bottom of the bank × Comparative Example 1 TOTM was used as the first child bag of Example 1. The same polymer alloy used in Example 1 without additives was used. Table 1 shows the platelet aggregation ability and the deformation state of the bag when treated in the same manner as in Example 1.

Comparative Example 2 A polyvinyl chloride bag (sheet thickness 250 μm) containing 35% by weight of dioctyl phthalate was used as the first child bag of Example 1, and platelet aggregation and buffing were treated in the same manner as in Example 1. The deformation state of is shown in Table 1.

Table 1 As is clear from Table 1, 1 to 20% by weight of TOTM
The added Example of the present invention had a small amount of TOTM exuded into platelets, had platelet aggregation ability even after 72 hours, and no deformation of the bag was observed even after strong centrifugation. Next, the bags manufactured in Example 2 and Comparative Example 2 were tested for oxygen permeability, carbon dioxide gas permeability, and water vapor permeability using the methods shown below. The results are shown in Table 2. (1) Oxygen permeability measured according to ASTM-D-1434.

(2) Carbon dioxide gas permeability Measured according to AST 110-1434.

(3) Water vapor transmission rate Measured according to JIS-Z-0208.

As is clear from Table 2, the bag of the present invention exhibits a gas permeability that is approximately 3.5 times higher in oxygen permeability and approximately 2.7 times higher in carbon dioxide permeability than the bag of the comparative example, Approximately 1 in water smoke permeability
/3.6, it can be seen that this bag is superior to the bag of Comparative Example 2 as a platelet storage bag.

〔effect〕

By storing platelets in a bag made of the polymer alloy of the present invention, platelets can be safely stored for a long period of time with less adhesion and aggregation of platelets to the bag surface. This bag has appropriate oxygen permeability and carbon dioxide gas permeability, and has desirable properties as a platelet storage bag. In addition, by using this platelet storage bag as a child bag of a composite bag, the surface of the bag of the present invention will not be deformed even during high-speed rotation when separating platelets from plasma by strong centrifugation, and the bag will not be accidentally dropped. However, the bag will not be damaged from the deformed parts.

Further, even when the platelet storage bag of the present invention is used to accommodate whole blood preparations containing red blood cells, hemolysis is small and it can be used as a parent bag for a composite bag.

[Brief explanation of the drawings] Figure 1 shows a schematic diagram of the composite bag. In the figure, 1 is a blood donor, 2, 4, 6, 8, and 10 are tubes, 3 is a parent bathog, 5 is a first child bag, 7 is a switching valve, and 9 is a second child bag. 1. Case Description 1990 Patent Application No. 14506 2. Name of the invention: Platelet storage bag and composite bag using the same 3.
Relationship with the case of the person making the amendment

Claims (2)

[Claims] (1) (a) 25 to 60% by weight of poly(ethylene butylene) polystyrene block copolymer (b) 20 to 40% by weight of polypropylene (c) 5 to 35% by weight of ethylene acrylate copolymer A coalesced mixture having at least two or more portions in which the polystyrene segments of the block copolymer of (a) are crystallized and arranged,
1 to 20% by weight of trimellitic acid tri-n-octyl ester, tri-2-ethylhexyl trimellitate, or a mixture thereof is added to the polymer alloy in which the molecular chains of the polymers a) to (c) are entangled in a network. A platelet storage bag made of mixed resin. (2) A parent bag that accommodates donor blood and separates blood components, a child bag that stores the separated blood components, and a system for communicating the parent bag and the child bag to transport the separated blood components. A composite bag comprising a tube, wherein the child bag comprises the platelet storage bag according to claim 1.