JPS5967958A - Resin composition for medical device - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a resin composition suitable for constructing medical equipment, particularly infusion storage bags, blood storage containers, tubes for blood circuits of artificial kidneys, and the like.

BACKGROUND ART Conventionally, blood bags have been used as medical equipment, for example, to transport and store blood, and blood circuit tubes have been used when performing dialysis using an artificial kidney for patients with renal failure.

The properties required for these materials are that they must be flexible and not change in quality, and even if they come into contact with blood for a long time, they must not change the quality of the blood or transfer foreign substances into the blood. or,
Blood circuit tubes are transparent so that the blood passing through them can be observed from the outside, flexible enough to be deformed freely, and the tube quickly returns to its original shape when clamped or removed from the outside of the tube. However, it requires anti-elasticity that allows the blood flow to be stopped or allowed to flow at any time during this operation, and a non-adhesive surface that prevents the tubes from adhering to each other when they are wrapped or stacked. be done.

Conventionally, medical devices such as blood bags for transporting and storing blood, tubes for blood circuits for artificial dialysis, etc. have been molded from compositions made by adding dioctyl phthalate (hereinafter referred to as DOP) as a plasticizer to vinyl chloride resin. It has been obtained through processing.

However, in compositions in which DOP is added to vinyl chloride resin, there is a concern that DOP may be eluted into the blood and have an adverse effect on the human body. In order to eliminate such drawbacks, for example, as disclosed in JP-A-56-139519, 20 to 300 parts by weight of vinyl chloride is grafted to 100 parts by weight of an ethylene/vinyl acetate/hypogen oxide copolymer. By polymerizing, the various physical properties necessary for medical equipment as described above, such as recovery from tightening of the flanges, rebound resilience, and non-stickiness between tubes or sheets, are brought to a satisfactory level. .

However, when such graft copolymers are used to mold various medical devices, acetic acid and hydrochloric acid are likely to be eliminated, and therefore, when they come into contact with blood, they may have a harmful effect on blood cells and cause hemolysis. This made it unsuitable for medical equipment use.

As a result of repeated studies to solve the above-mentioned problems, the present inventors have found a composition that suppresses the desorption of acetic acid, hydrochloric acid, etc. and is suitable for use in medical equipment.

The gist of the present invention is to provide a graft copolymer obtained by graft polymerizing vinyl chloride to an ethylene-carbon oxide-vinyl acetate copolymer, and a graft copolymer obtained by graft polymerizing vinyl chloride to an ethylene-carbon oxide-vinyl acetate copolymer, Expression (a) or naka) or 0
It is an aliphatic carboxylic acid residue represented by →.

(a) -R, -C-C-R2 \1 HHHH 1111 (b) -Rs CCR4CCRs \/ \ 1 0 0 HHHHHH l 1 1 1 1.1 (
/i -Rs -C-C-R7C-C-Rs -C-C
-R*\/ \/ \1 0 0.

(However, each of R1 to R9 is a saturated hydrocarbon group or an unsaturated hydrocarbon group having a prime number of 1 to 25.) A resin composition for medical equipment, characterized by containing a glycerin ester represented by The graft copolymer -■- used in the present invention is
Vinyl chloride-111-11iisiwaws-■ in a fixed ratio of 1 to ethylene-carbon oxide-vinyl acetate copolymer
--@Fist--1 Obtained by graft polymerization. In that case, the terpolymer has 60% ethylene by weight.
Preferably, the composition contains 20 to 40 parts of vinyl acetate and 5 to 20 parts of carbon oxide, and has a weight average molecular weight of 20,000 to 1,000,000. Then, 20 to 500 weight parts of vinyl chloride is graft-polymerized to 100 parts by weight of the terpolymer. Furthermore, it contains other monomers that can be copolymerized with vinyl chloride, such as α-olefins such as ethylene and propylene, vinyl esters such as vinyl acetate and vinyl stearate, and vinyl ethers such as methyl vinyl ether and cetyl vinyl ether. You may do so. The monomer particularly preferably used together with vinyl chloride in the above graft polymerization is ethylene, in which case ethylene is preferably used in a ratio ranging from 2 to 25 parts by weight per 100 parts by weight of vinyl chloride. A composition with particularly excellent transparency and flexibility can be obtained.

In order to graft-polymerize vinyl chloride to the above terpolymer, for example, water, a dispersant, and the terpolymer are added to an autoclave equipped with a stirrer, and then vacuum suction is applied to remove oxygen present in the autoclave. do. Then, while stirring,
Add vinyl chloride and dissolve the terpolymer in the vinyl chloride over 0.5 to 3 hours. Thereafter, a polymerization initiator is added and the temperature is raised while stirring is continued. The pressure is raised so that the temperature inside the autoclave reaches 50 to 80°C, and this temperature is maintained for 5 to 15 hours to allow the graft polymerization reaction to proceed.

In order to assist in dispersing the vinyl chloride solution in which the terpolymer is dissolved, partially oxidized polyvinyl alcohols, cellulose derivatives such as methylcellulose, hydroxymethylcellulose, and carboxymethylcellulose are used as dispersants.
Polyvinylpyrrolidone and other surfactants can be used.

The type of polymerization initiator added differs depending on whether suspension polymerization or emulsion polymerization is performed. To carry out suspension polymerization, organic peroxides such as benzoyl/(-oxide, lafuroyl peroxide, di-2-ethylhexyl/<-oxydicarbonate, etc.) are used. Ammonium sulfate, potassium persulfate, etc. are used.These polymerization initiators are used in a proportion of 0.02 to 0.3% by weight based on vinyl chloride.

Vinyl chloride is preferably added in excess of 5 to 50% by weight over the amount of vinyl chloride to be graft polymerized.
The weight ratio of the total amount of the terpolymer and vinyl chloride used during polymerization to the aqueous medium is preferably 1:12 to 1:3.

The end point of the polymerization can be determined from the relationship between the internal pressure of the polymerization vessel and the amount of vinyl chloride grafted, which was previously obtained through experiments.

After polymerization, unreacted vinyl chloride is removed, and then
The suspension or emulsion in the autoclave is filtered to remove water to obtain polymer particles. The polymer particles are then washed with water and dried before use.

The graft copolymer obtained in the above manner has good transparency and flexibility, but does not exhibit hemolysis or cytotoxicity.
Cheap.

Therefore, in the present invention, as a result of various studies in order to improve hemolysis and cytotoxicity without impairing transparency and flexibility, we have found that by incorporating a glycerin ester represented by a specific chemical formula, hemolysis and cytotoxicity can be improved. The toxicity was improved.

The glycerin ester used in the present invention is represented by the following formula.

1 CHz-0-C-X 0 1 CH-0-C-Y 11 CH2-0-C-Z The above x, y, zVi are each represented by the following formula (a) or (b) or e→ It is an aliphatic carboxylic acid residue.

H 1 0 HHHHHH o 0 0 Above (
R1 to R9 in a), (b), and (/9) are all saturated hydrogenated hydrogen groups or unsaturated hydrogenated groups having 1 to 25 carbon atoms.

Examples of carboxylic acid residues corresponding to formula (A) above include 3-hexenoic acid, 4-hexenoic acid, 4-decenoic acid, 9-hexenoic acid, and 9-hexenoic acid.
-cundecenoic acid, 4-dodecenoic acid, 5-dodecenoic acid,
Examples include oleic acid, elaidin i, erucic acid, etc., which are epoxidized by oxidizing the double bond in the molecule.

Examples of carboxylic acid residues corresponding to formula (b) above include double bonds in molecules such as 9.12-hexadecadienoic acid, 9.12-octadecadienoic acid, icosadienoic acid, docosadienoic acid, and hexacosienic acid. Examples include those that have been oxidized and epoxidized.

Examples of carboxylic acid residues corresponding to the above formula (/→ Examples include those obtained by oxidizing and epoxidizing.

The oxirane oxygen content #-f in the chrycerin ester of 1iQE is 5 to 10% by weight, and the iodine number is 10.
The following are preferred.

It is the percentage by weight of one molecule of Ryarin ester. If it is less than 5% by weight, the improvement of hemolysis and cytotoxicity of the composition tends to be incomplete, and if the amount is as high as 10% by weight, blood It is easy to lose suitability for use as medical equipment due to elution into infusions and infusions.

The iodine value is the number of iodine absorbed in the glycerin ester Roof, and the glycerin ester is more susceptible to changes over time than IO.

Glycerin esters mentioned in IQ are those that do not have aromatic rings in their molecules, but this is because having aromatic rings makes it impossible to meet safety standards as medical equipment. be.

The composition obtained by containing the graft copolymer and a glycerin ester represented by a specific chemical formula does not exhibit hemolysis or cytotoxicity, and has desirable properties as a resin composition for medical equipment. be.

The amount of the glycerin ester used is preferably in the range of 3 to 20 parts by weight per 100 parts by weight of the graft copolymer.

If the amount of the glycerin ester is as small as 100 parts by weight of the graft copolymer and 3 parts by weight, hydrochloric acid, acetic acid, etc., which are harmful to blood components such as red blood cells, can be sufficiently eliminated from the graft copolymer. It tends to be difficult to suppress,
Furthermore, if the amount of the glycerin ester is greater than 20 parts by weight, surface tackiness increases and mechanical strength tends to decrease.

In order to improve the aging resistance of the composition of the present invention, stabilizers, plasticizers, etc. can be added within a range that does not have a harmful effect on the two-part composition.

As stabilizers, for example, calcium stearate, zinc stearate, magnesium oxide, solenite ester wood antioxidant shavings, phenol thread antioxidants, etc. are used, and as plasticizers, dioctyl heptatarate, dioctyl adipate, etc. are used. I can do it.

The above-mentioned composition is pre-kneaded using a conventional melt-mixing means, such as a mixing roll, a mixed-wire extruder, a Henschel-type suit mixer, etc., and then molded into a thermoplastic material such as daring, blow molding, vacuum forming, press molding, etc. This can be done by applying resin molding means.

According to the present invention, it has excellent transparency and flexibility, has almost no surface stickiness, has excellent elastic properties, and does not change the quality of body fluids such as blood when it comes in contact with them. The resin composition has no adverse effects and is suitable for medical device applications.

The resin composition for medical equipment of the present invention can be suitably used for molding medical equipment such as medical catheters, tubes for blood transfusions and infusions, blood bags, infusion bags, and tubes for blood circuits in artificial dialysis.

Examples of the present invention are described below. In the examples, parts are simply parts by weight.

Example 1 A terpolymer consisting of 55 parts of ethylene, 32 parts of vinyl acetate, and 18 parts of carbon oxide was used, and 110 parts of vinyl chloride were polymerized with 27 parts of vinyl chloride per 100 sK of the terpolymer. A graft copolymer was used.

As a glycerin ester, glycerin is esterified with a ratio of 50% 9.12-octadecadienoic acid, 45% oleic acid, and 596% lyric acid, and then epoxidized by an oxidation reaction.
% liquid material was used.

To 100 parts of the above graft copolymer, 10 parts of the above glycerin ester was added, and the mixture was mixed with two rolls.
The mixture was thoroughly kneaded at 150°C, and then formed into a sheet with a thickness of α4ms using an inverted calendar roll.

This sheet had excellent transparency, exhibited no hemolytic effect or cytotoxicity, and contained almost no eluate, and satisfied each item specified in the Test Method for Plastic Containers for Infusions. In addition, the stickiness on the plane was extremely slight.

Therefore, it was suitable as a sheet for infusion bags.

Example 2 For 100 parts of a terpolymer (55 parts of ethylene, 32 parts of vinyl acetate, 18 parts of -carbon oxide) as a graft copolymer, 103 parts of vinyl chloride, 15 parts of ethylene, 7
A sheet was prepared in exactly the same manner as in Example 1 except that a polymerized material was used.

This sheet has extremely excellent transparency and flexibility, exhibits no hemolytic action or cytotoxicity, and has very little eluate.
(April 6, 2016) It satisfied each item specified by K. In addition, the stickiness of the flat surface was extremely slight, and no damage was caused by autoclave sterilization treatment (121° C., 1 atm, steam heating for 20 minutes). Therefore, it was suitable as a sheet for blood bags.

Example 3 As a glycerin ester, glycerin was esterified with a ratio of 5096% of 9,12-octadecadienoic acid, 40% of oleic acid, and 1096% of lyric acid, and then jepoxidized by an oxidation reaction. A tube having an inner diameter of 4.5% and an outer diameter of 6.5% was produced by extrusion molding in the same manner as in Example 2, except that a liquid material having a value of 496 was used.

A blood circuit was created using this tube, and standards for artificial mice for dialysis (draft) (Japan Medical Glass Association, 1932)
As a result, it satisfied all the criteria stipulated in the standards, including dissolution and hemolytic properties, and was suitable as a tube for an artificial kidney blood circuit.

patent applicant Sekisui Chemical Co., Ltd.

Claims (1)

[Scope of Claims] L: A graft copolymer obtained by graft polymerizing vinyl chloride treated with an ethylene-carbon oxide-vinyl acetate copolymer, and a graft copolymer obtained by graft polymerizing vinyl chloride, and a graft copolymer obtained by graft polymerization of the following formula % [However, x, y, and z are each It is an aliphatic carboxylic acid residue represented by the following formula (a), (b), or (c). \ 1 HHHH \ / \ 1 0 0 HHHHHH o 0 0 (
However, R1 to R9 are all saturated hydrocarbon or unsaturated hydrocarbon groups having 1 to 25 carbon atoms. . z The resin composition for medical equipment according to claim 1, wherein the oxirane oxygen content in the glycerin ester is 5 to 10% by weight and the iodine value is 1O or less.