JPS6023623B2 - Medical equipment resin composition - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a resin composition for medical equipment, particularly a resin composition suitable for constructing equipment for preserving blood, fluid, etc.

As medical equipment, for example, blood bags are used to transport and store blood, and blood circuit tubes are used when performing dialysis using an artificial kidney for patients with kidney failure.

Blood bags and tubes for blood circuits must not alter the blood in any way even if they come into contact with blood for a long time, and must not transfer foreign substances into the blood or absorb components in the blood. . In addition, the blood bag is transparent so that the blood inside it can be observed accurately from the outside, is flexible enough to be deformed freely, is suspended with blood in it, and is almost permanently stretched and distorted. None, must have cleave resistance. Blood circuit tubes are similarly required to have transparency, flexibility, and creep resistance. BACKGROUND ART Conventionally, a composition in which a large amount of dioctyl phthalate is added to vinyl chloride resin has been used as a molding material for blood bags and tubes for blood circuits.

Although this composition has excellent flexibility and transparency, the disadvantage is that the dioctyl phthalate contained in the composition elutes into the blood and is eventually absorbed and accumulated in the body. . In addition, blood bags made of compositions containing a large amount of dioctyl phthalate are sometimes sterilized using ethylene oxide gas, but in such cases, ethylene oxide has a tendency to absorb and retain ethylene oxide. However, it also had the disadvantage that ethylene oxide could not be easily removed after sterilization. The present inventors have improved the drawbacks of vinyl chloride resin compositions containing dioctyl phthalate, and have excellent flexibility and transparency, mechanical strength such as excellent creep resistance, and As a result of intensive research into a composition that is rich in polyethylene and suitable for use as a resin for molding medical devices, we have combined a graft copolymer obtained by graft polymerizing vinyl chloride onto an ethylene-vinyl acetate copolymer and a thermoplastic urethane elastomer. The present inventors have discovered that desired properties can be obtained by the following methods, and have completed the present invention. That is, the gist of the present invention is as follows: 1. A graft copolymer obtained by graft polymerizing vinyl chloride to an ethylene-vinyl acetate copolymer in which the copolymerization amount of vinyl acetate is 50 to 8% by weight, and a thermoplastic Resin composition for medical equipment 2 characterized by comprising urethane elastomer Copolymerization content of vinyl acetate is 5
0 to 8% by weight of ethylene-vinyl acetate copolymer, vinyl chloride and the general formula (wherein, X is a hydrogen atom or a methyl group, and Y is a hydrogen atom or an alkyl group having 1 to 18 carbon atoms) be.

) and a thermoplastic urethane elastomer. Next, the resin composition for medical equipment of the present invention will be explained in more detail.

Ethylene-vinyl acetate copolymer (hereinafter referred to as E) in the present invention
It is abbreviated as VA.

), the copolymerization content of vinyl acetate is set in the range of 50 to 80% (hereinafter % indicates weight %). This is because if the amount of vinyl acetate copolymerized is outside this range, the resulting resin composition will lack transparency and flexibility, or exhibit hemolysis and cytotoxicity, making it unsuitable for use as a resin composition for medical equipment. ,
This is because you will only get something unsuitable. EVA is usually
It is obtained by suspension polymerization, emulsion polymerization, and high pressure polymerization.
However, as it is, EVA lacks tear strength, tensile strength, etc., and is therefore brittle and cannot be used as a resin for molding medical equipment. Therefore, in the present invention, a graft copolymer obtained by graft polymerizing vinyl chloride to EVA, or a graft copolymer obtained by graft polymerizing vinyl chloride to EVA, or a general formula (where x is a hydrogen atom or a methyl group, and Y is a hydrogen atom or a carbon The number is 1 to 18 alkyl groups.

) is obtained by graft polymerization, which imparts mechanical strength suitable for use as a component of resin compositions for medical equipment, and further improves rebound resilience, transparency, flexibility, etc. Granted. As EVA, those obtained by suspension polymerization, particularly those obtained by aqueous suspension polymerization, are suitable.

When EVA obtained by suspension polymerization is used, a graft copolymer that is optimal as a component of a resin composition for medical equipment can be obtained, and one that does not exhibit hemolysis or cytotoxicity can be obtained. The graft copolymerization content of vinyl chloride in the graft copolymer is preferably 30 to 90%, and if the amount of vinyl chloride in the graft copolymer exceeds 90%,
Even if a medical device is molded using a composition containing the obtained graft copolymer as a component, the flexibility will be poor, and the composition containing the obtained graft copolymer as a component will be less than 30%. Even if a medical device is molded using the composition, the molded product tends to exhibit blocking and is likely to be inferior in strength.

To graft-polymerize vinyl chloride in the presence of EVA with a vinyl acetate content of 50 to 80%, for example, EVA, pinyl chloride, water, a dispersant, etc. are mixed to form an aqueous suspension.
React using a radical polymerization initiator. As the dispersant, for example, partially saponified polyvinyl acetate, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, sodium polyacrylate, polyvinylpyrrolidone, etc. with a degree of saponification of 70 to 90 mol % are used. As the radical polymerization initiator, lauroyl peroxide, benzoyl peroxide, azobisisobutyronitrile, t-butyl peroxide carbonate, etc. are used. These dispersants and polymerization initiators have been conventionally used in aqueous suspension polymerization of pinyl chloride, and in the present invention, those conventionally used in this technical field, including these, can be used as appropriate without particular restriction. .

In addition, during the above graft polymerization, the weight temperature is 55 to 700.
0 is preferred. In this way, pinyl chloride is graft-polymerized to EVA in an aqueous suspension, followed by sedimentation, dehydration,
A graft copolymer is obtained by drying, and the amount of dispersant contained in the graft copolymer is preferably 0.5% or less, preferably 0.1% or less. If the amount of dispersant in the graft copolymer exceeds 0.5%, when a medical device is molded using a composition containing the obtained graft copolymer as a constituent component, dispersion will occur from the molded product. The drug tends to elute and exhibit hemolytic and cytotoxic effects. The graft copolymer of the present invention may contain, in addition to vinyl chloride, other monomers that can be copolymerized with the vinyl chloride, such as ethylene, propylene, vinyl olefinic acid, vinyl acetate, vinyl stearate, etc. Vinyl esters, methyl vinyl ether, vinyl ethers such as cetyl vinyl ether, etc. may be contained as a graft polymerization component. These other monomers may be contained in a proportion of 20% or less so as not to impair the flexibility and transparency of the molded article obtained from the graft copolymer. Furthermore, in the present invention, EVA is combined with vinyl chloride and the general formula (wherein x is a hydrogen atom or a methyl group, and Y is a hydrogen atom or an alkyl group having 1 to 18 carbon atoms).

) may be used as a component of the composition.
Examples of the monomer represented by the above general formula include acrylic acid, methacrylic acid, methyl acrylate,
Methyl methacrylate t-butyl acrylate, butyl methacrylate, 2-ethylhexyl acrylate, 2-
These include acrylic esters and methacrylic esters such as ethylhexyl methacrylate, stearyl acrylate, and stearyl methacrylate.

The monomers are preferably used in a weight ratio of 0.01 to 1 to 1 part vinyl chloride. Further, the monomer may be added together with vinyl chloride all at once before the start of the graft polymerization, or may be added continuously during the weight, or may be added in portions.Similarly to the above, the monomer may be added to the graft polymerization by suspension polymerization in the presence of EVA. can be made to do so. Vinyl chloride and the monomer are randomly polymerized with EVA to form a graft copolymer.

When the monomer is graft-polymerized to EVA together with vinyl chloride, a product with much better transparency can be obtained than when only vinyl chloride is graft-polymerized to EVA. The above monomer is preferably contained in an amount of about 5% as a graft polymerization component in the graft copolymer, and vinyl chloride is preferably contained in an amount of about 40 to 45% as a graft polymerization component. A graft copolymer obtained by graft polymerizing vinyl chloride to EVA, and EV
The graft copolymers obtained by graft polymerizing A with vinyl chloride and the above monomers themselves have excellent transparency and flexibility, and do not exhibit soluble properties or cytotoxicity, making them suitable for use as medical devices. Although it is suitable as a resin for molding, it lacks the property of quickly returning to its original shape when deformed (i.e., anti-twill elasticity), and it also has the property of elongation under sustained load, i.e., creep. It has the disadvantage that it is prone to distortion (distortion).

Therefore, the present inventors conducted repeated studies to obtain a composition that is rich in rebound elasticity and does not cause creep distortion without impairing the advantages of the graft copolymer. It has been discovered that when used in combination with a graft copolymer, it has excellent rebound resilience and creep resistance.

The term "thermoplastic polyurethane elastomer" refers to a thermoplastic linear polymer having urethane bonds and having rubber-like elasticity at room temperature.

The thermoplastic polyurethane elastomer used in the present invention includes 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, 4,4-toluene diisocyanate, and the like.
'-diphenylmethane diisocyanate, 1,5 naphthalene diisocyanate, W, W, m-xylylene diisocyanate, w, w', p-xylylene diisocyanate, etc. are used, and compounds that react with isocyanate are used. Depending on the type, it is divided into two types: ether type and ester type.

As the ether thermoplastic polyurethane, polytetrahydrofuran, 1,4-butanediol, 1,4cis-butenediol, polypropylene glycol, polyoxypropylene glycol, etc. are used as diol components. As the ester thermoplastic polyurethane, polyesters made of adipic acid and ethylene glycol, polyesters made of adipic acid and ethylene glycol, polyesters made of caprolactone and butanediol, polycaprolactone, etc. are used as the ester thermoplastic polyurethane. As the thermoplastic polyurethane elastomer, both the ether type and ester type mentioned above can be used, but the ether type thermoplastic polyurethane elastomer is particularly suitable, as it is water resistant and stable over a wide range of pH values. A composition with excellent chemical resistance can be obtained.

The mixing ratio of the thermoplastic polyurethane elastomer to the graft copolymer is preferably in the range of 5 to 80 parts by weight based on the weight of the graft copolymer 10.

To mix the thermoplastic polyurethane elastomer with the graft copolymer, the thermoplastic polyurethane elastomer is melt-kneaded using a mixing roll, extrusion kneader, etc. to form the graft copolymer. Conventional methods for uniform mixing can be applied. In the present invention, in order to improve the thermal stability and aging resistance of the resulting composition, conventionally known stabilizers and plasticizers are added to the resin composition within the range that does not have a harmful effect on blood etc. It may be mixed inside. As the stabilizer, for example, calcium stearate, zinc stearate, barium stearate, etc. can be used, and as the plasticizer, epoxidized soybean oil, dioctyl phthalate, etc. can be used. Furthermore, the obtained graft copolymer may contain a vinyl chloride resin, a vinyl chloride-ethylene copolymer, an ethylene-carbon oxide-vinyl acetate copolymer, etc. that are compatible with the graft copolymer. These resins usually make up 20% or less of the graft copolymer. According to the present invention, it is possible to obtain a composition that not only has excellent flexibility and transparency, does not exhibit blood pressure or cytotoxicity, but also has excellent rebound and creep resistance, and is suitable for molding medical devices. be able to. Furthermore, in the resin composition for medical equipment of the present invention, like the conventional European vinyl chloride resin composition, a low-molecular plasticizer such as dioctyl phthalate, polyester, polyester, polyester, etc. are added to the vinyl chloride resin.
Since it is not necessary to add a large amount of a polymeric plasticizer such as urethane, the elution of the plasticizer from the molded product can be substantially eliminated, and problems in molding processing can be avoided.

Therefore, the resin composition of the present invention can be suitably used for molding medical equipment such as catheters, blood transfusion and infusion tubes, blood bags, and infusion bags.

Examples of the present invention are listed below.

In the examples, "parts" means parts by weight. Each test in the Examples was conducted as follows.

KMn04 consumption due to eluate: Tsumugi tube 30 minutes,
The test liquid was prepared by boiling 300% of distilled water at 121°C for 3 minutes and cooling it to room temperature.
20% of 1N KMn04 solution and 1.0% Z of dilute sulfuric acid were added, boiled for 3 minutes, and after cooling, KIO. Add 1 evening, 0.01
Bottle with N sodium thiosulfate solution.

Separately, using blank test liquid 20', perform the same operation to obtain both KM.
The difference in consumption of n04 liquid was taken as the measured value.

The standard value is 1.0 or less. Dish resistance test: Conducted in accordance with the test method for plastic containers for infusions in the Japanese Pharmacopoeia's "General Test Methods."

Deformation recovery of the clamped part: After the tube was attached vertically with a clamp from the outside for a certain period of time, the clamp was removed, and the time until the flattened tube returned to its original shape was measured.

The load when attaching the tube with the clamp was set so that a load of 2k9 was applied to a 7% width portion along the length of the tube. Examples 1-2 170 parts of pure water, 0.5 parts of hydroxypropyl methyl cellulose and 0.5 parts of methyl cellulose as a dispersion were added and dissolved in an autoclave equipped with a fly trawl machine, and then vinyl acetate obtained by suspension polymerization was added. After adding 45 parts of EVA with a content of 60% and purging the inside of the autoclave with nitrogen, 55 parts of vinyl chloride was added, and while shaking the autoclave, the temperature inside the autoclave was raised to 50 qC to dissolve EVA in the vinyl chloride.

Thereafter, 0.1 part of lauroyl peroxide was added to form a suspension, and the mixture was reacted at 70 qo for 6 hours. - After this, unreacted vinyl chloride was removed, the remaining suspension was dehydrated, and the graft copolymer was separated and dried. The thus obtained graft copolymer contained 50% vinyl chloride and 50% EVA. 1 part (Example 1), 20 parts (Example 2) of thermoplastic urethane elastomer to the above-mentioned graft copolymer 10
mixed in the ratio of As the thermoplastic urethane elastomer, a heavy body obtained by reacting 4, ediphenyl diisocyanate and polypropylene glycol was used.

Furthermore, 0.5 parts and 0.1 parts of calcium stearate and zinc stearate, respectively, and 5 parts of epoxidized soybean oil were added as heat stabilizers, and after kneading at 150 qo for 5 minutes using a mixing roll, the rolled sheet was mixed. Created ``I got a bellet from this.

For comparison, a beret containing only the graft copolymer and no thermoplastic urethane elastomer was prepared. Using these pellets, the outer diameter is 7.0m/m and the inner diameter is 4.6m/m.
A tube of m is formed by extrusion molding, and a tube of K is formed by extrusion.
Mn04 consumption and melting plate tests were conducted.

- Shore hardness at 000 and 20q0 was measured to further evaluate flexibility, and deformation recovery of the clamp tightening part was evaluated to evaluate anti-twill elasticity and creep resistance.

The above results are shown in the columns of Examples 1 and 2 in Table 1.

Separately, a test using the same machine was conducted on a tube formed from a pellet made of the graft copolymer alone, and the amount of KMn04 consumed by eluate was 0.4 cm, and there was no hemolysis in the hemolysis test.

In addition, the Shore hardness was 76 (000), 50 (20° C.), and the deformation recovery after vertical clamping was 3 minutes after leaving it for 1 hour and 120 minutes after 5 hours. Table 1 shows that by adding a thermoplastic urethane elastomer to the graft copolymer, there was almost no increase in the amount of KMn04 reducing substance in the eluate and hemolysis, making it suitable as a resin composition for medical equipment. This was recognized.

It has also been found that the addition of thermoplastic urethane elastomer provides sufficient flexibility and is extremely effective in shortening the time required for deformation recovery of the vertically attached portion of the clamp. Further, the tube molded from the above composition had extremely excellent transparency and no coloration was observed. Example 3~
4 Copolymerization amount of vinyl acetate obtained by suspension polymerization: 60
Graft polymerization was carried out in the same manner as in Examples 1 and 2, except that 5 parts of vinyl chloride and 5 parts of 2-ethylhexyl acrylate were added to 45 parts of % EVA. Ethylhexyl acrylate graft polymerization content: 5%, EVA copolymerization content: 50%
% of the graft copolymer was obtained.

To this graft copolymer, thermoplastic urethane elastomer 1 anchor (Example 3) and 2 foundation (Example 4) were added to the same machine as Examples 1 and 2, and after mixing with bran, a pellet was prepared. Chews were extruded using The obtained tubes were subjected to the same tests as in Examples 1 and 2, and the results are shown in the Examples 3 and 4 columns of Table 1. From the results of Examples 3 and 4 in Table 1, the graft copolymer obtained by graft polymerization of vinyl chloride and 2-ethylhexyl acrylate to which a thermoplastic urethane elastomer was added resulted in an increase in KMn04 reducing substances in the eluate and hemolysis.・Almost no plasticity was observed, and it was found to be suitable as a resin composition for molding medical equipment.

Claims (1)

[Scope of Claims] 1. A graft copolymer obtained by graft polymerizing vinyl chloride to an ethylene-vinyl acetate copolymer in which the copolymerization amount of vinyl acetate is 50 to 80% by weight, and a thermoplastic urethane elastomer. A resin composition for medical equipment, characterized by comprising: 2. The resin composition for medical equipment according to claim 1, wherein the ethylene-vinyl acetate copolymer is obtained by suspension polymerization. 3. Claim 1, wherein the graft polymerization content of vinyl chloride in the graft copolymer is 30 to 90% by weight.
The resin composition for medical equipment according to item 1 or 2. 4 Ethylene-vinyl acetate copolymer with vinyl acetate copolymerization content of 50 to 80% by weight has vinyl chloride and general formula ▲ mathematical formula, chemical formula, table, etc. ▼ (However, in the formula, X is a hydrogen atom or Methyl group, Y is a hydrogen atom or has 1 to 18 carbon atoms
number of alkyl groups. 1. A resin composition for medical equipment, comprising a graft copolymer obtained by graft polymerization of a monomer represented by the following formula, and a thermoplastic urethane elastomer. 5
The resin composition for medical equipment according to claim 4, wherein the ethylene-vinyl acetate copolymer is obtained by suspension polymerization. 6. Claim No. 6, which is a graft copolymer in which vinyl chloride and the monomer represented by the general formula ▲There are numerical formulas, chemical formulas, tables, etc.▼ are randomly polymerized to an ethylene-vinyl acetate copolymer. The resin composition for medical equipment according to item 4 or 5. 7. The resin composition for medical equipment according to any one of claims 4 to 6, wherein the thermoplastic polyurethane elastomer is an ether-based thermoplastic polyurethane elastomer.