JPH0611287B2 - Platelet storage bag and composite bag using the same - Google Patents

Description

TECHNICAL FIELD The present invention relates to a bag for preserving platelets and a composite bag using the same, and more specifically, it does not cause adhesion of platelets to the surface of the bag, and chemicals from the inner surface of the bag. The present invention relates to a bag for storing platelets that can be stored for a long time without exuding a substance, and a composite bag using the same.

[Conventional technology]

Conventionally, a polyvinyl chloride bag containing a plasticizer such as dioctyl phthalate is known as a platelet storage bag for safely storing collected platelets for a long period of time and supplying it when needed. The permeability was low, and the platelets were likely to adhere to the surface of the bag, and the platelet aggregating ability was lowered when the platelets were supplied. Further, the bag exhibits blocking properties during high-pressure steam sterilization, and the inner surfaces are in close contact with each other, making it difficult to supply platelets into the bag. Furthermore, since this bag contains a plasticizer in polyvinyl chloride, if the platelets are stored in the bag for a long period of time, the plasticizer will migrate into the platelets, and platelet function such as low osmotic shock recovery rate Had the drawback of decreasing

As a plastic composition for blood bags that has improved these drawbacks, a polymer composition obtained by mixing polypropylene and ethylene vinyl acetate copolymer (or polyethylene) with polyethylene butylene polystyrene block copolymer is introduced in Japanese Patent Publication No. Sho 62-19461. Has been done.

The platelet storage bag is also used as a composite bag that stores blood collected from a donor in a parent bag, separates blood components, and stores platelets in a child bag. As a composite bag using the polymer composition introduced in JP-A-55-60464
No. is known.

[Problems to be solved by the invention]

Since the bag made of this polymer composition does not contain a plasticizer, the disadvantage that the added substance exudes into the platelets was solved, but the elastic modulus in the high temperature region was low and the bag softened and deformed when sterilized under high pressure steam. I did it. In particular, a bag prepared by mixing an ethylene vinyl acetate copolymer in a polymer mixture generates acetic acid due to thermal decomposition during molding or hydrolysis during high-pressure steam sterilization, which is released and mixed into the platelet concentrate, resulting in platelet concentrate. There was a drawback to make the acid.

[Means for Solving the Problems]

The present inventor, as a result of diligent studies in order to improve these drawbacks of the prior art, formed from a polymer alloy obtained by mixing an ethylene acrylate copolymer in a polymer mixture of polyethylene butylene polystyrene block copolymer and polypropylene. By using the bag for storage of platelets, it was found that there is no exudation of chemical substances into platelets, little deformation at high or low temperatures, good gas permeability and a bag capable of storing platelets for a long period of time can be obtained. The present invention has been reached.

That is, the present invention is a polymer having a composition of (a) polyethylene butylene polystyrene block copolymer 25 to 60% by weight (b) polypropylene 20 to 40% by weight (c) ethylene acrylate copolymer 5 to 35% by weight. A mixture of at least two polystyrene segments of the block copolymer of (a), wherein
A bag for preserving platelets, which is formed from a polymer alloy in which molecular chains of the polymers (c) to (c) are entwined in a mesh.

Further, the present invention is for storing the blood of the donor and for transporting the separated blood components by connecting the parent bag for separating the blood components, the child bag for storing the separated blood components, and the parent bag and the child bag. Is a composite bag made of the above tube, and the child bag material is a composite bag made of the polymer alloy.

Furthermore, the present invention is the above composite bag, wherein the material of the parent bag is polyvinyl chloride containing dioctyl phthalate.

[Action]

The present invention, a mixture of polyethylene butylene polystyrene block copolymer and polypropylene of a specific mixing ratio, by adding an ethylene acrylic acid ester copolymer, ethylene acrylic acid ester copolymer, polyethylene butylene polystyrene block copolymer and It acts as a compatibilizer for polypropylene to form a polymer alloy. And a bag formed using this polymer alloy has little fluctuation in mechanical properties at high or low temperatures,
Since it is flexible and has excellent transparency, it is ideal for storing platelets.

〔Example〕

In the block copolymer used in the present invention, the hard segment has a structure of polystyrene or its copolymer, and the soft segment has a structure of ethylene butylene copolymer. The molecular weight of polystyrene or its copolymer used as a hard segment is 5,000 to 120,000. The ethylene butylene copolymer, which is a soft segment, has a molecular weight of 10,0.
It can be obtained by reacting 00 to 250,000 polybutadiene with polystyrene to form a poly (ethylene butylene) polystyrene block copolymer, and then hydrogenating the block copolymer.

The ethylene butylene copolymer, which is a soft segment, has a composition ratio of ethylene and butylene of 40 to 60/60 to 40 mol%, and the proportion of the soft segment in the block copolymer is 60 to 90% by weight. Excellent physical properties and flexibility can be obtained. The amount of the block copolymer used is in the range of 25 to 60% by weight in the polymer mixture, and if the amount is less than 25% by weight, the flexibility of the bag tends to be poor, and exceeds 60% by weight. And the moldability tends to deteriorate.

Next, the polypropylene used in the present invention is polypropylene alone or a copolymer composed mainly of polypropylene. Examples of the copolymer component include ethylene and butene-1, and the proportion thereof is 10% by weight or less. Polypropylene has the property of improving the strength when formed into a bag, and the strength is remarkably improved by mixing it with another polymer in a specific ratio to form a polymer alloy. The range of the amount of such polypropylene used is 20 to 40% by weight in the polymer mixture. If it is less than 20% by weight, the transparency and strength of the bag tend to deteriorate, and if it exceeds 40% by weight, the flexibility tends to deteriorate.

Next, the ethylene acrylic acid ester copolymer used in the present invention acts as a compatibilizing agent for the block copolymer and polypropylene and contributes to the formation of a polymer alloy. However, the acrylic acid ester used here is methyl acrylate. , Ethyl acrylate, butyl acrylate, etc., and their proportion in the copolymer component is 5 mol% or more. When the amount of acrylic ester is less than 5 mol%,
Transparency tends to be poor. The ethylene acrylic acid ester copolymer accounts for 5 to 35% by weight in the polymer mixture, but if it is less than 5% by weight, the dispersion of the polymer becomes poor,
Extrudability and transparency are also poor, especially the low temperature properties tend to be poor, and if it exceeds 35% by weight, the mechanical strength tends to be low.

To mold the bag, these polymers were put into a blender and mixed uniformly, and then the polymer mixture was melted and extruded into a medical bag-shaped mold and blow-molded or extruded into a sheet. After that, the ends are heat-sealed to manufacture a medical bag. The thickness of the sheet can be appropriately selected according to its application, for example, 200 to 450.
is μ. When the homogeneously mixed polymer mixture is melt extruded and molded, it has at least two portions where two or more polystyrene segments, which are hard segments of the block copolymer, are crystallized and arranged, and block copolymerization is performed. The soft segment of the coalescing, the crystallization of the block copolymer, the non-arranged hard segment, and the molecular chains of polypropylene and ethylene acrylate copolymer form a polymer alloy having a chemical structure in which they are entangled in a mesh. Since the polymer mixture has a polymer alloy structure, mechanical strength, especially at low temperature, the mechanical properties can be maintained while maintaining flexibility, and oxygen and carbon dioxide gas permeability can also be improved, making it a platelet storage bag. As a result, it has preferable characteristics.

Next, an example of using the platelet storage bag of the present invention as a child bag of a composite bag will be described with reference to FIG.

FIG. 3 is a schematic explanatory view of a composite bag, in which 1 is a 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, and 9 Indicates the second child bag.

Blood collected from the donor 1 is stored in the parent bag 3,
It is separated into blood cell components and plasma components by a centrifuge. As a material for the parent bag 3, a plastic containing a plasticizer is preferable, and polyvinyl chloride is particularly preferable. As the plasticizer, dioctyl phthalate is preferable because the hemoglobin content in the supernatant is small. The content of the plasticizer in the polymer can be appropriately selected depending on the type of the plasticizer and the combination with the polymer, but is, for example, 10 to 50% by weight.

The plasma component separated in the parent bag 3 passes through the tube 4,
Transfer from the tube 6 to the first child bag 5. The first child bag 5 is made of a material made of the polymer alloy. Further, the first child bag 5 is separated into platelets and other plasma components by a centrifugal separator, and the plasma components other than platelets are transferred from the tube 6 through the tube 8 to the second child bag 9. The platelets are then stored and stored in the first child bag 5.

Examples of the material of the second child bag 9 include the above-mentioned polymer alloy, polyvinyl chloride containing dioctyl phthalate, polyvinyl chloride containing 2-ethylhexyl trimellitate, and the like. The plasma components other than the platelets contained in the second child bag 9 are usually frozen and stored.

The present invention will be described below with reference to examples.

Example 1 40% by weight of polyethylene butylene polystyrene block copolymer (Kreton G-1650 manufactured by Shell Chemical Co., Ltd.), 30% by weight of polypropylene (FL-6711N manufactured by Sumitomo Chemical Co., Ltd.), ethylene ethyl acrylate copolymer (15 mol of ethyl acrylate) %, And 30 wt% of DPDJ6182 manufactured by Nippon Unicar Co., Ltd. were mixed by a mixer, melted at 200 ° C. and extruded into a sheet to produce a sheet having a thickness of 320 μ. This sheet is first
The test sample shown in the table was provided and compared with the sheet of Comparative Example 1.

Comparative Example 1 40% by weight of polyethylene butylene polystyrene block copolymer (Clayton G-1650 manufactured by Shell Chemical Co., Ltd.), 30% by weight of polypropylene (Sumitomo Chemical Co., Ltd.), 30% by weight of ethylene vinyl acetate copolymer (vinyl acetate content 15%) % Were mixed in the same manner as in Example 1, melt-extruded and cooled at 200 ° C. into a sheet (thickness: 320 μ). The test results of the sheet are shown in Table 1.

The test shown in Table 1 was conducted by the following method.

(1) Hydrolysis test 10 g of a sample and 30 g of water were added to a pressure vessel, heated at 130 ° C. for 2 hours, and the decomposition product in water was measured by gas chromatography.

(2) Dynamic elastic modulus It was measured by Vibron.

As is clear from Table 1, the sheet of Example 1 which is the bag material of the present invention has a superior dynamic elastic modulus in the high temperature region and the low temperature region as compared with the sheet of Comparative Example 1 and is softened and deformed at high temperature. It also indicates that the sheet of the present invention does not cure even at low temperature.

Further, acetic acid was detected in the sheet of Comparative Example 1 by hydrolysis at high temperature, but neither ethanol nor acetic acid was detected in the sheet of the present invention, indicating that the bag material of the present invention is suitable as a material for storing platelets. .

Example 2 and Comparative Example 2 54% by weight of polyethylene butylene polystyrene block copolymer (Clayton G-1650 manufactured by Shell Chemical Co., Ltd.), 23% by weight of polypropylene (FL-6711N manufactured by Sumitomo Chemical Co., Ltd.), ethylene ethyl acrylate copolymer (ethyl An amount of acrylate of 15 mol% and 23 wt% of DPDJ6182 manufactured by Nippon Unicar Co., Ltd. were mixed by a mixer, melted at 200 ° C. and extruded into a sheet to prepare a sheet having a thickness of 250 μ.

The ends of the two sheets and the ports were melted to form a medical bag. On the other hand, in the bag of Comparative Example 2, 40% by weight of dioctyl phthalate was mixed with polyvinyl chloride, melted at 130 ° C. and extruded into a sheet to form a sheet having a thickness of 250 μ.
A bag was manufactured in the same manner as in Example 2. Rabbit blood was placed in this bag at 1200 rpm for 10 minutes, and the platelet concentrate obtained by centrifugation was placed in the bag, and shaken horizontally at 22 ° C for about 2 days.
The time course of ADP and collagen aggregability are shown in FIGS. 1 and 2.

Each measurement method was carried out by using NKK Hemattracer 1 manufactured by Nikko Bioscience Co., Ltd., and adding reagents so that the final concentration was 40 μmol. / Ml for ADP and 10 μg / ml for collagen.

Comparing both bags at the time when the measured value of each agglutination capacity becomes half of the blank value, the bag of the present invention has an ADP agglutination capacity of about 1.6.
Approximately 2.0 times longer storage period was observed with collagen aggregation ability.

The bags produced in Example 2 were then tested for oxygen permeability, carbon dioxide permeability and water vapor permeability. Similarly, the same test was performed on the bag of Comparative Example 2. The results are shown in Table 2. The oxygen permeability and carbon dioxide gas permeability in Table 2 were measured according to ASTM-D-1434, and the water vapor permeability was measured according to JIS-Z-0208.

As is clear from Table 2, the bag of the present invention has a gas permeability of about 3.1 times in oxygen permeability and a carbon dioxide gas permeability of about 2.5 times in comparison with the bag of the comparative example, and has a water vapor permeability of about 1/100. Since it is 3.5, it is superior to the bag of Comparative Example 2 as a bag for storing platelets.

Into the bag produced in Example 2, the platelet concentrate of human obtained by using a blood collection device V-50 manufactured by Haemonetics Co.,
Platelets were stored at 22 ° C. with horizontal shaking and collected every 24 hours for aggregation test. The results are shown in Table 3.

In Table 3, ADP10 and ADP20 are each 10 times the final concentration of ADP reagent.
And 20 μmol. / Ml were added, CLG5 and CLG
10 is collagen reagent at final concentration of 5 and 10 μg / ml, respectively
The aggregating ability when added is shown. See also Table 3 [5 days / 0
[Day] is calculated by (aggregation ability on day 5) / (initial aggregation ability) × 100.

As is clear from Table 3, the bag of the present invention showed a smaller decrease in the aggregating ability of ADP and collagen after 5 days, as compared with the polyvinyl chloride bag of Comparative Example. It is shown to be excellent as a bag for storing platelets.

Examples 3 to 8 The weight ratios of the block copolymer, polypropylene and ethylene ethyl acrylate copolymer used in Example 1 were variously changed as shown in Table 4 to prepare polymer mixtures.
Sheets (thickness 250 μm) were produced by melt extrusion at 0 ° C.
The mechanical properties of this sheet were tested at each temperature and the results are shown in Table 4.

Among the measurement items shown in Table 4, the transparency was visually determined as follows.

○ Good transparency △ Slightly opaque × Opaque As is clear from Table 4, the sheets of Examples 3 to 6 of the present invention are superior in tensile strength and transparency as compared with the sheets of Examples 7 and 8 tested for comparison.

Example 9 The bag produced in Example 2 was subjected to an eluate test using three types of test methods. The results are shown in Table 5.

The bag of the present invention passed the test in any test method.

Example 10 In FIG. 3, dioctyl phthalate as a parent bag
The storage condition of blood was tested when polyvinyl chloride containing 35% was used. The results are shown in Table 6.

Example 11 In Example 10, the preservation state of blood was examined when polyvinyl chloride containing 40% of 2-ethylhexyl trimellitate was used as a parent bag. The results are shown in Table 6.

Comparative Example 3 In Example 10, the preservation state of blood was examined when the polymer alloy used in Example 1 was used as the parent bag. The results are shown in Table 6.

The measurement method in Table 6 is to collect 0.2 cc of blood in the parent bag before blood storage and after 3 weeks of blood storage, and use ATP in blood.
Content, 2,3-DPG content and supernatant hemoglobin were performed as follows. The carbon dioxide partial pressure was measured by collecting 0.5 cc of blood. The measuring methods in Table 6 are as follows.

ATP content (μmol. / GHb) Measured by the enzyme method of Boehringer's ATP measurement kit.

2,3-DPG content (μmol. / GHb) Measured by enzyme method using Boehringer DPG measurement kit.

Hemoglobin in supernatant (mg / dl) Measured by the azide hemoglobin method of the hemoglobin measurement kit of Nippon Shoji Co., Ltd.

As is clear from Table 6, the parent bags of Examples 10 and 11 in which the plasticizer was mixed with polyvinyl chloride had a large carbon dioxide partial pressure and a small ATP content and a 2,3-DPG content. Particularly, the bag of Example 10 using dioctyl phthalate as a plasticizer is preferable because the hemoglobin in the supernatant is small.

〔effect〕

By storing platelets in a bag made of the polymer alloy of the present invention, adhesion of platelets to the bag surface, little aggregation, no functional deterioration such as low osmotic shock recovery rate, and safe storage of platelets for a long period of time Became possible. In addition, this bag maintains its flexibility even at low temperatures,
It is also suitable for cryopreservation of platelets at -20 ° C or lower because its mechanical properties do not deteriorate. Further, this bag does not soften and deform even in a high temperature region, and decomposition products are not generated by thermal decomposition or hydrolysis, so that high-pressure steam sterilization is possible.

This bag has appropriate oxygen permeability and carbon dioxide gas permeability, and has desirable characteristics as a bag for storing platelets.

In addition, by using this platelet storage bag as a child bag of a composite bag, it has become possible to separate and store the blood collected from a donor in each component.

[Brief description of drawings]

1 and 2 show the time-dependent changes in the platelet aggregation ability of rabbit blood. FIG. 1 shows the ADP aggregation ability and FIG. 2 shows the collagen aggregation ability. FIG. 3 shows a schematic explanatory view of the composite bag. In the figure, 1 is a 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, and 9 is a second child bag.

Claims (3)

[Claims] 1. A polymer having a composition of (a) polyethylene butylene polystyrene block copolymer 25 to 60% by weight (b) polypropylene 20 to 40% by weight (c) ethylene acrylate copolymer 5 to 35% by weight. A mixture of at least two polystyrene segments of the block copolymer of (a), wherein
A bag for preserving platelets, which is formed from a polymer alloy in which the molecular chains of the polymer of (c) are intertwined in a mesh shape. 2. A parent bag that stores blood of a donor and separates blood components, a child bag that stores the separated blood components, and a parent bag and a child bag that communicate with each other to transport the separated blood components. A composite bag consisting of a tube for use, wherein the child bag is made of the material according to claim 1. 3. The composite bag according to claim 2, wherein the material of the parent bag is polyvinyl chloride containing dioctyl phthalate.