JPH0356739B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION BACKGROUND OF THE INVENTION Technical Field The present invention relates to a novel resin composition for blood storage containers. Specifically, the present invention relates to a vinyl chloride-based graft copolymer composition for blood storage containers that has good flexibility and heat resistance, is capable of high-frequency welding, and has excellent gas permeability. Prior Art As is well known, blood has a self-protective effect, and when blood comes into contact with a different interface other than the inner wall of a blood vessel, platelets adhere to the different interface, aggregation, and gelation of plasma, that is, formation of crosslinked fibrin. Formation occurs.
In conventional blood bags, platelets in the blood aggregate to the plastic interface that is the base material of the blood bag, and 6 hours after blood collection, the platelet aggregation ability decreases to about 60% of the time when blood was collected, and after another 24 hours, the platelet aggregation ability decreases to about 60%. It drops to 40%. On the other hand, from the point of view of the effective use of current platelet preparations, it is necessary to develop storage containers made of plastic that can store blood for longer periods of time, storage containers made of so-called blood-compatible plastic, or local medical devices. desired. Currently, plastic containers and other medical devices made of soft vinyl chloride resin are widely used due to their good processability, flexibility, transparency, low water vapor permeability, heat resistance, etc. ing. These soft vinyl chloride resins contain phthalate esters such as di-2-ethylhexyl phthalate (hereinafter referred to as DOP) as plasticizers.
Contains 60%. However, since phthalate esters have a high migration property, it is known that when a blood storage container is made from the above-mentioned soft vinyl chloride resin, the phthalate esters are eluted into blood plasma. For this reason, it has been reported that when phthalate esters dissolve into plasma containing platelet concentrates, they also reduce the aggregation ability, which is a function of platelets. [Japanese Journal of Blood Transfusion 28 , 282 (1982)]. In addition, the soft vinyl chloride resin containing the phthalate ester plasticizer has insufficient gas permeability, and the shelf life of blood bags made using this resin is usually only 6 hours, which is a short period of time. do not have. In other words, soft vinyl chloride resin has a carbon dioxide gas permeability coefficient of approximately 2.0×10 ³ ml・mm/m ²・atm・day,
In the blood bag using this, the expiration date of the platelet plasma concentrate was 6 hours. However, this permeability coefficient is 2.5×10 ³ to 9.0×10 ³ ml・mm/m ²・atm・day
More preferably 3.0×10 ³ to 8.0×10 ³ mlmm/m ² .
By using atm-day, the shelf life of platelets was improved, and a pH of 6 or higher, which is considered to be able to effectively preserve platelets, was maintained for more than 72 hours. 2.5
If it is below, the CO ₂ concentration generated by platelet metabolism will increase and the PH will decrease, making it impossible to expect long-term preservation of platelets. Also, if it is larger than 9.0,
Platelet metabolism is overactivated and platelet function is likely to be impaired in a short period of time. Note that by keeping the permeability coefficient within the above range, the preservation stability of other blood cells can also be improved. Therefore, if the amount of the plasticizer is increased, gas permeability will be improved, but if the amount is increased, practical mechanical strength will be lost. Therefore, the gas permeability that allows long-term storage of blood cells such as platelets, i.e. 2.5×10 ³ to 9.0
It is difficult to obtain ×10 ³ ml・mm/m ²・atm・day. On the other hand, polyester plasticizers are used as non-migratory plasticizers. Since this polyester plasticizer is generally composed mainly of fatty acid ester, it is well known that it is inferior to phthalate esters having a phenyl group as a skeleton in terms of water resistance, hydrolysis resistance, etc. On the other hand, as a blood bag material with relatively good gas permeability, 10 to 40% by weight of polypropylene and
A resin composition consisting of a blend with 40 to 85% by weight of a thermoplastic elastomer is known (Japanese Patent Application Laid-open No.
No. 55-60464), such polyolefin resins have poor adhesive properties, so high frequency fusion is difficult during secondary processing, and molding methods are limited. Additionally, it lacks the flexibility that occurs when soft polyvinyl chloride is used. OBJECT OF THE INVENTION Accordingly, an object of the present invention is to provide a novel resin composition for blood storage containers. Another object of the present invention is to provide a vinyl chloride-based graft copolymer composition for blood storage containers that has good flexibility and heat resistance, is capable of high-frequency welding, and has excellent gas permeability. These objectives are such that the amount of styrene-butadiene copolymer and/or its derivative is 20 to 100 parts by weight of the vinyl chloride portion obtained by reacting the styrene-butadiene copolymer and/or its derivative with vinyl chloride. This is achieved by a resin composition for blood storage containers comprising a graft copolymer and a stabilizer in a proportion of 200 parts by weight. The present invention also provides a resin composition for a blood storage container, in which the styrene-butadiene copolymer and/or its derivative portion is 30 to 120 parts by weight based on 100 parts by weight of the vinyl chloride portion. Furthermore, the present invention is a resin composition in which the derivative of the styrene-butadiene copolymer is an epoxidized product, a halide, or a maleated product of the styrene-butadiene copolymer. Also,
The present invention is a resin composition in which the stabilizer is contained in an amount of 0.05 to 5 parts by weight based on 100 parts by weight of the graft copolymer. DETAILED DESCRIPTION OF THE INVENTION The graft copolymer used in the present invention is a new compound, which is obtained by reacting a styrene-butadiene copolymer and/or a derivative thereof with vinyl chloride. The amount of the graft copolymer and/or its derivative portion is from 20 to 200 parts by weight, preferably from 30 to 120 parts by weight. This is because if the amount of the copolymer or its derivative is less than 20 parts by weight, the graft copolymer will have low flexibility, while if it exceeds 200 parts by weight, the mechanical strength will decrease and high frequency fusion will become difficult. It is from. Such a graft copolymer can be produced, for example, by charging vinyl chloride and a styrene-butadiene copolymer or a derivative thereof into a reactor in the above-mentioned proportions, and then subjecting the vinyl chloride to suspension polymerization in the presence of a radical polymerization catalyst. can get. The graft copolymer thus obtained is purified by washing with water or alcohol, if necessary. The styrene-butadiene copolymer used is
The molar ratio of styrene to butadiene is 1:1 to 1:
10, preferably a 1:2 to 1:6 random or block copolymer, the molecular weight of which is 50,000 to 50,000.
200,000, preferably 70,000 to 190,000. Examples include CALIFLEX TR-110 (Ciel Chemical Co., Ltd.), CALIFLEX TR-1107 (Ciel Chemical Co., Ltd.), Solprene (Asahi Kasei Co., Ltd., Philips Co., Ltd.), Tuffprene (Asahi Kasei Co., Ltd.), Clayton G (Ciel Chemical Co., Ltd.), etc. be. Examples of derivatives thereof include epoxides, halides, and maleates of the styrene-butadiene copolymer. Stabilizers blended into the resin composition of the present invention include metals such as calcium and zinc, stearic acid, lauric acid, ricinoleic acid, naphthenic acid,
There are metal soaps with fatty acids such as 2-ethylhexoic acid, and one or more of these are added to 100 parts by weight of the graft copolymer.
It is blended in an amount of 0.05 to 5 parts by weight, preferably 0.1 to 3 parts by weight. In addition to the above-mentioned stabilizers, epoxidized vegetable oils such as epoxidized soybean oil and epoxidized linseed oil may also be used as stabilizing aids, such as 30 parts by weight or less, preferably 5 to 20 parts by weight, per 100 parts by weight of the graft copolymer. Parts by weight can be blended. Furthermore, in the resin composition of the present invention, a polymer plasticizer can also be blended. Examples of polymeric plasticizers include ethylene copolymers, such as ethylene-
Vinyl acetate-ketone copolymers [e.g. Elvaloy 742.
Co., Ltd.], polyesters such as polycaprolactone-g-(polystyrene), polyε-caprolactone [e.g. PCL 300, PCL 700 (and above, Union
Carbide) polyester (e.g. Nuoplaz)
6187 (manufactured by Tenneco Chemicals), Paraplex G-
25, Paraplex G-54 (manufactured by Rohm & Haas), Admex 761 (manufactured by Ashland Chemicals), etc.]
etc. Among these, the above-mentioned ethylene copolymer (eg, Elvaloy 742) exhibits particularly excellent effects. These polymeric plasticizers are blended in an amount of 150 parts by weight or less, preferably 10 to 90 parts by weight, based on 100 parts by weight of the graft copolymer. Furthermore, lubricants and other additives can also be used as long as they do not exhibit toxicity. The resin composition according to the present invention can be molded using commonly used press molding machines, extrusion molding machines, injection molding machines, blow molding machines, inflation molding machines, calendar molding machines, and the like. A blood storage container can be obtained by assembling and processing these molded products using a high frequency fusion machine or the like. The resin composition obtained in this way has good transparency and flexibility, good heat resistance, allows high frequency fusion, and has a carbon dioxide permeability coefficient of 2.5 × 10 ³ to 9.0.
×10 ³ ml・mm/m ²・atm・day (30℃) preferably
3.0×10 ³ ~8.0×10 ³ ml・mm/m ²・atm・day (30℃)
It is. Next, a case in which a blood collection bag is manufactured using the resin composition of the present invention will be described with reference to the drawings. That is, the blood sample indicates a blood bag, and the blood collection bag 3 made of the resin composition of the present invention, which is equipped with a plurality of peel-tab-equipped discharge ports 1 and 2, is heated by high-frequency heating or other heating. A blood collection tube 6 made of the resin composition of the present invention is connected to the blood collection bag, which is heat-sealed and communicates with the internal space 5 of the blood collection bag. The internal space of this blood collection bag contains ACD-1 as an anticoagulant.
Solution A (e.g. 2.20 g of sodium citrate, 0.80 g of citric acid and 2.20 g of glucose in 100 ml of aqueous solution)
g), CPD solution (e.g. 0.327 g of citric acid, 2.63 g of sodium citrate, 0.251 g of sodium dihydrogen phosphate, dextrose in 100 ml of aqueous solution)
Contains 2.32g), etc. Further, a blood sampling needle 7 is attached to the tip of the blood sampling tube 6. A cap 8 is attached to this blood collection needle. In addition, when connecting a child bag in addition to the blood collection bag 3, the peripheral part 10 is heat-sealed and the internal space 11 is heat-sealed like the resin composition bag of the present invention equipped with a peel tab-equipped outlet 9. A first child bag 13 having a communicating tube 12 made of the resin composition of the present invention is connected to the connecting outlet 2 of the blood collection bag 3 via a branch pipe 14 by a connecting needle 15 at the tip of the connecting tube. 16. Further, a connecting tube 21 made of the resin composition of the present invention is provided with a discharge port 17 with a peel tab, has a peripheral edge 18 sealed with high frequency, and communicates with the internal space 19.
The connecting tube 21 of the child bag 22 is connected to the connecting tubes 12 and 16 via the branch pipe 14. The above was explained using blood bag as an example,
Other blood storage containers can also be used in the same manner. Next, the present invention will be explained in more detail by giving Examples. Examples 1 to 5 Epoxidized soybean oil (O -130P) and 1 part by weight of a Ca-Zn stabilizer (Mark 593) was extruded to 0.4 mm.
A thick sheet was obtained. The sheet was transparent and the hemolytic and cytotoxicity test results were similar to the control solution, showing no hemolytic or cytotoxic properties.
In addition, carbon dioxide permeability was tested and the results were as shown in Table 1. Among them, those of Examples 2 to 5 sometimes showed better carbon dioxide permeability than that of Comparative Example 1. Comparative Example 1 5 parts by weight of epoxidized soybean oil (O-130P) per 100 parts by weight of polyvinyl chloride with an average degree of polymerization of 1300,
A vinyl chloride resin composition obtained by blending 1 part by weight of a Ca-Zn stabilizer and 25 parts by weight of DOP was extrusion molded to obtain a sheet with a thickness of 0.4 mm. When this sheet was subjected to the same tests as in Examples 1 to 5, the results were as shown in Table 1. Comparative Example 2 The styrene-butadiene copolymers used in Examples 1 to 5 were blended in the same proportions as in Examples 1 to 5 to 100 parts by weight of polyvinyl chloride having an average degree of polymerization of 1300, and this mixture Epoxidized soybean oil and Ca--Zn stabilizer were mixed in the same proportions to parts by weight to obtain a sheet with a thickness of 0.4 mm. This sheet had low mechanical strength and was not suitable for practical use. Examples 6 to 10 Epoxidized soybean oil (O -130P) 5 parts by weight,
A resin composition containing 1 part by weight of Ca-Zn stabilizer (Mark 593) and 60 parts by weight of styrene-vinyl acetate-ketone copolymer (Elvaloy 742) was extruded to obtain a 0.4 mm thick sheet. Ta. This sheet was transparent and flexible, the hemolytic toxicity test and cytotoxicity test results were comparable to the control solution, and it did not exhibit hemolytic or cytotoxic properties, making it suitable as a sheet for blood bags. Further, when carbon dioxide gas permeability was tested, the results were as shown in Table 2. Among them, those of Examples 7 to 10 showed particularly superior carbon dioxide gas permeability than that of Comparative Example 3. Comparative Example 3 A sheet was obtained by blending in the same manner as in Comparative Example 1 except that the amount of DOP was increased to 50 parts by weight. When this sheet was subjected to the same tests as in Examples 6 to 10, the results were as shown in Table 2.

【table】

[Table] Example 11 In order to examine the effect of improving gas permeability of the resin composition according to the present invention, polyvinyl chloride and polyvinyl chloride were mixed so that the resin composition of Example 9 and the styrene-butadiene copolymer were in the same ratio. Styrene-butadiene copolymer was dissolved and mixed in tetrahydrofuran, reprecipitated with methanol, and epoxidized soybean oil, Ca-Zn stabilizer, and Elvaloy 742 were blended in the ratio shown in Table 3, and the mixture was mixed to a thickness of 0.4 mm. A sheet was prepared and the carbon dioxide permeability coefficient was measured, and the results were as shown in Table 3.

[Table] Example 12 Regarding the sheet of Example 8 and the sheet of Comparative Example 3, the number of platelets attached to the sheet surface and the separation of their morphology were measured, and the results were as shown in Table 4. Table 4 Example 8 Comparative Example 3 Total number of adherents 157 257 Number of molds in total number of adherents 66 113 Percentage of molds (%) 42 44 Experimental method 95,000/mm ³ platelet suspension was dropped onto the sample surface. The number of attached platelets and morphological changes of attached platelets were observed after leaving for 30 minutes. In addition, in the classification evaluation, the platelet type is one in which the platelets are expanded and formed on a flat plate. Example 13 Sheets each having a thickness of 0.4 mm were prepared from the resin composition of Example 8 and the resin composition of Comparative Example 3, and then high frequency welded to form bags. 3 ml of concentrated platelet plasma was added to this bag using ACD-A solution as a storage solution, and when the sheet was stored at 22°C for 72 hours, the carbon dioxide gas permeability and PH changes of the sheet were observed, and the results shown in Table 5 were obtained. Obtained.

[Table] Maintaining the PH during platelet storage has an important meaning for the platelet survival rate of transfused blood. It is clear that the decrease in the value was smaller than that of Comparative Example 3, and that the function was maintained well during platelet storage. Specific Effects of the Invention As described above, the resin composition for blood storage containers according to the present invention is characterized in that 100 parts by weight of vinyl chloride is obtained by reacting vinyl chloride with a styrene-butadiene copolymer and/or a derivative thereof. 20 to 200 parts by weight of the styrene-butadiene copolymer and/or its derivative, preferably 0 to 200 parts by weight.
Since it is composed of 120 parts by weight of a graft copolymer and a stabilizer, it has good flexibility and heat resistance, is capable of high frequency welding, and has excellent gas permeability, especially carbon dioxide gas permeability. There is. In addition, since the styrene-butadiene copolymer and/or its derivative portion is 20 to 200 parts by weight, preferably 30 to 120 parts by weight, per 100 parts by weight of the vinyl chloride portion, carbon dioxide gas permeability is particularly good. .
Further, the resin composition according to the present invention is free of hemolytic toxicity and cytotoxicity, has low platelet adhesion and morphological change, and has low PH change, and is therefore extremely useful as a material for medical devices such as blood bags. It is also useful as a packaging material for contents that undergo metabolism, such as vegetables.

[Brief explanation of drawings]

The drawing is a front view showing an example of a medical device using the resin composition according to the present invention. 3...Blood bug, 13,22...Child bug,
6, 16, 21...Tube.

Claims (1)

[Scope of Claims] 1. The styrene-butadiene copolymer and/or its derivative portion is based on 100 parts by weight of the vinyl chloride portion obtained by reacting the styrene-butadiene copolymer and/or its derivative with vinyl chloride.
A resin composition for a blood storage container comprising a graft copolymer and a stabilizer in a proportion of 20 to 200 parts by weight. 2. The resin composition for a blood storage container according to claim 1, wherein the derivative of the styrene-butadiene copolymer is an epoxidized product, a halide, or a maleated product of the styrene-butadiene copolymer. 3. The resin composition for a blood storage container according to claim 1 or 2, which contains 0.05 to 5 parts by weight of a stabilizer based on 100 parts by weight of the graft copolymer. 4 Carbon dioxide permeability coefficient is 2.5×10 ³ to 9.0×10 ³ ml・
The resin composition for a blood storage container according to any one of claims 1 to 3, which has a particle size of mm/m ² ·atm ·day.