JPS639543B2 - - Google Patents

Description

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

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 are flexible and unchanging,
Even if it comes into long-term contact with blood, it must not alter the quality of the blood or transfer foreign substances into the blood.

In addition, blood circuit tubes are transparent so that the blood passing through them can be observed from the outside, and are flexible enough to be deformed freely, allowing the tube to quickly return to its original shape when clamped or removed from the outside of the tube. Resilience that allows the tubes to recover and allow blood flow to stop or flow at any time by this operation, and a non-adhesive surface that prevents tubes from sticking to each other when wrapped or stacked. etc. are required.

By the way, blood bags and tubes for blood circuits have conventionally been made from compositions made by adding a large amount of dioctyl phthalate to vinyl chloride resin. Although this composition has excellent flexibility and transparency, the disadvantage is that dioctyl phthalate is slightly eluted, absorbed into the body through the blood, and accumulated. In addition, blood circuit tubes are sometimes brought into contact with ethylene oxide gas for sterilization, but in such cases, their tendency to absorb ethylene oxide has also been considered a drawback.

Therefore, there was a need to create a resin composition for constructing blood bags and tubes for blood circuits that does not have these drawbacks.

The present inventors focused on the fact that the above-mentioned vinyl chloride resin containing dioctyl phthalate is already in use, although it has some drawbacks, and has passed the test standards set forth in the Japanese Pharmacopoeia and the Ministry of Health and Welfare notification. attempted to overcome the above drawbacks by improving vinyl chloride resins and creating resin compositions that do not use dioctyl phthalate.

They have also discovered that a ternary copolymer of ethylene, carbon monoxide, and vinyl acetate is effective as a method for softening vinyl chloride resin without substantially using a plasticizer.

However, terpolymers of ethylene, carbon monoxide, and vinyl acetate tend to generate low-molecular-weight decomposition products when heated during molding or when left for long periods of time. As a result of further intensive studies, it was discovered that by incorporating a proton-donating organic compound, a composition that did not exhibit hemolysis or cytotoxicity could be obtained. The present invention has now been completed.

The gist of the present invention is (a) vinyl chloride resin, (b) ethylene/carbon monoxide/vinyl acetate copolymer, and (c)
A resin composition for medical equipment containing a proton-donating organic compound.

Next, the resin composition for medical equipment of the present invention will be explained in more detail.

The vinyl chloride resin used in the present invention is not limited to a vinyl chloride homopolymer, but may be a vinyl chloride copolymer. Copolymers of vinyl chloride include vinyl chloride and other monomers, such as α-olefins such as ethylene and propylene; vinyl esters such as vinyl acetate and vinyl stearate;
Acrylic acid, methacrylic acid and acrylic acid esters and methacrylic acid esters such as methyl acrylate, methyl methacrylate, butyl acrylate, butyl methacrylate, 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, stearyl acrylate, and stearyl methacrylate; methyl vinyl ether, cetyl vinyl ether unsaturated acids such as maleic acid, maleic anhydride, and fumaric acid, and their esters; styrene, acrylonitrile, vinylidene chloride, and the like.

Among the vinyl chloride resins mentioned above, particularly preferred are copolymers of vinyl chloride and ethylene, with an ethylene copolymerization content of 4 to 15% by weight, and a degree of polymerization in the range of 1000 to 3000. belongs to.

The ethylene carbon monoxide/vinyl acetate copolymer used in the present invention is commercially available, for example, "Elvaloy 741" manufactured by Dupont. Carbon monoxide and 0.1 to 0.9 parts by weight of vinyl acetate are copolymerized under high pressure using a radical polymerization catalyst. Ethylene/carbon monoxide/vinyl acetate copolymer is 5 parts per 100 parts by weight of vinyl chloride resin.
It is preferable to use it in a proportion of 200 parts by weight.
Excellent flexibility and transparency can be obtained as a resin composition for medical equipment. However, when ethylene/carbon monoxide/vinyl acetate copolymers are heated during molding or left for long periods of time, they tend to generate low molecular weight decomposition products, which can cause hemolysis and cell death. Since toxicity is likely to occur, a proton-donating organic compound is included in order to prevent hemolysis and cytotoxicity.

The proton-donating organic compound in the present invention is
When protons are exchanged between molecules, an organic compound having the property of giving protons is used, such as an organic compound having an alcoholic hydroxyl group or an organic compound having an amine group.

Examples of organic compounds having alcoholic hydroxyl groups include saturated higher aliphatic alcohols such as nonyl alcohol, decyl alcohol, myristyl alcohol, cetyl alcohol, and stearyl alcohol; glycerin monooleate, glycerin monostearate, polyglycerin monostearate, and pentaerythritol. Partial ester compounds of polyhydric alcohols such as monostearate, dipentaerythritol distearate, sorbitan laurate, sorbitan palmitate, sorbitan stearate, and sucrose aliphatic ester are used.

Examples of organic compounds having an amine group include saturated aliphatic amines such as nonylamine, decylamine, dodecylamine, and heptadecylamine; diamine monoamide compounds such as tetramethylene diamine monostearate and hexamethylene diamine monostearate; histidine, arginine, Basic amino acid compounds such as lysine and polymers thereof are used.

Among the proton-donating organic compounds mentioned above, particularly preferred are glycerin monostearate, hexamethylene diamine monostearate and polylysine.

The proton-donating organic compound is preferably added in an amount of 0.01 to 15 parts by weight per 100 parts by weight of the vinyl chloride resin and the ethylene/carbon monoxide/vinyl chloride copolymer. If the amount of the proton-donating organic compound used is less than 0.01 parts by weight, the effect of suppressing hemolytic properties and cytotoxicity of the composition will be insufficient, and conversely, if the amount used is more than 15 parts by weight, tends to have undesirable effects such as reducing the transparency and strength of the composition.

The proton donating organic compound renders the composition non-hemolytic and non-cytotoxic. this is,
The proton-donating organic compound forms hydrogen bonds with the carbonyl and carboxyl groups present in the ethylene/carbon monoxide/vinyl acetate copolymer, thereby eliminating acetic acid from the copolymer. and also by scavenging acetic acid present freely in the composition.

In the present invention, fine magnesium oxide powder and/or fine calcium oxide powder may be further added. It is desirable that both the magnesium oxide fine powder and the calcium oxide fine powder have a particle size of 50 μm or less.

Magnesium oxide fine powder and calcium oxide fine powder are based on 100 parts by weight of the vinyl chloride resin and the ethylene/carbon monoxide/vinyl acetate copolymer.
Preferably, it is added in a proportion ranging from 0.01 to 5 parts by weight.

Furthermore, in order to improve the thermal stability and aging resistance of the composition of the present invention, conventionally known stabilizers and plasticizers may be added to the composition within a range that does not have a harmful effect on blood etc. Can be blended. 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. As described above, the medical resin composition of the present invention contains a vinyl chloride resin, an ethylene/carbon monoxide/vinyl acetate copolymer, and a proton-donating organic compound, and therefore, the medical device obtained thereby can be used. has excellent flexibility and transparency, and exhibits no hemolytic or cytotoxic properties.

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 will be given below. The hemolysis test was conducted in accordance with the plastic container test method for infusions in the Japanese Pharmacopoeia "General Test Methods."

In addition, for the cytotoxicity test, the plastic to be tested is shredded, 1 g of this is taken, added to MEM medium, autoclaved at 121°C for 20 minutes, the extraction medium is diluted with control medium, and this is administered to the cells. The cells were cultured at 37° C. for 5 days at a CO ₂ concentration of 5%, and the number of cells and dead cells after 5 days were counted using a microscope, and toxicity was determined by comparing with a control solution. The amount of potassium permanganate consumed by the eluent was determined by adding ^1800cm2 of the plastic strips to be tested to 300ml of distilled water.
The test solution was boiled at 121℃ for 30 minutes and then cooled to room temperature.To 20ml of this test solution, 20ml of 0.01N potassium permanganate and 1.0ml of dilute sulfuric acid were added.
After boiling for 3 minutes and cooling, 0.1 g of potassium iodide was added and titrated with 0.01N sodium thiosulfate solution. Separately, 20 ml of a blank test solution was prepared, and the same procedure was performed to display the difference in the amount of potassium permanganate solution consumed between the two as a measured value.

Example 1 100 parts by weight of polyvinyl chloride (degree of polymerization 1050), ethylene/carbon monoxide/vinyl acetate copolymer (copolymerization content of ethylene 65% by weight, copolymerization content of carbon monoxide 10% by weight) 80 Parts by weight Glycerin monostearate 0.7 parts by weight, Calcium stearate 0.3 parts by weight
Parts by weight, 0.2 parts by weight of zinc stearate, and 5 parts by weight of epoxidized soybean oil were kneaded at 140°C using two rolls, and then kneaded using an inverted L-shaped calendar roll to form a sheet with a thickness of 0.4 mm.

This sheet had excellent transparency and flexibility, showed no hemolysis or cytotoxicity, and the amount of potassium permanganate consumed by the eluate was 0.7 ml, satisfying each item stipulated by medical standards.

Examples 2 to 5 In Example 1, instead of 0.7 parts by weight of glycerin monostearate, 0.7 parts by weight of tetraglycerin monostearate (Example 2), 0.7 parts by weight of pentaerythritol monostearate (Example 3), hexa Methylene diamine monostearate
A sheet was formed in exactly the same manner as in Example 1, except that 0.5 parts by weight (Example 4) and 0.3 parts by weight of polylysine (Example 5) were used, respectively, and then a cytotoxicity test and a hemolytic test were conducted. As a result, none of them showed any cytotoxicity or hemolytic properties.

In addition, the amount of potassium permanganate consumed by the eluate was 0.5 ml (Example 2), 0.6 ml (Example 3), and 0.3 ml.
(Example 4) and 0.4 ml (Example 5). The sheet thus obtained satisfied each item stipulated in the medical standards.

Examples 6 to 8 In Example 1, polyvinyl chloride (polymerization degree
1050) Instead of 100 parts by weight, a vinyl chloride/ethylene copolymer (degree of polymerization of 1800) with an ethylene copolymerization content of 9% was used, and 0.7 parts by weight of glycerin monostearate was replaced with pentaerythritol. The procedure was exactly the same as in Example 1, except that 0.5 parts by weight of monostearate (Example 6), 0.5 parts by weight of hexamethylene diamine monostearate (Example 7), and 0.3 parts by weight of polylysine (Example 8) were used. A sheet was formed, and then a cytotoxicity test and a hemolytic test were conducted.

As a result, none of them showed any cytotoxicity or hemolytic properties.

In addition, the amount of potassium permanganate consumed by the eluate
They were 0.5 ml (Example 6), 0.4 ml (Example 7), and 0.4 ml (Example 8). The sheet thus obtained is
It satisfied each item stipulated in the medical standards.

Comparative Example 1 Glycerin monostearate in Example 1
A sheet was formed in exactly the same manner as in Example 1, except that 0.7 parts by weight was not used, and then a cytotoxicity test and a hemolytic test were conducted, and this sheet showed cytotoxicity and hemolytic property. .

Furthermore, the amount of potassium permanganate consumed by the eluate was 1.5 ml, which was a high value. Therefore, this sheet was unsuitable for medical equipment.

Comparative Example 2 In Example 1, polyvinyl chloride (polymerization degree
1050) Instead of 100 parts by weight, a vinyl chloride/ethylene copolymer with an ethylene copolymerization content of 9% by weight (degree of polymerization 1080) is used, and 0.7 parts by weight of glycerin monostearate is not used. A sheet was formed in the same manner as in Example 1 except that
Next, a cytotoxicity test and a hemolytic test were conducted, but
This sheet showed cytotoxic and hemolytic properties.

Furthermore, the amount of potassium permanganate consumed by the eluate was 1.8 ml, which was a high value. Therefore, this sheet was unsuitable for medical equipment.

Claims (1)

[Scope of Claims] 1. A resin composition for medical equipment containing (a) a vinyl chloride resin, (b) an ethylene/carbon monoxide/vinyl acetate copolymer, and (c) a proton-donating organic compound. thing. 2. The resin composition for medical equipment according to claim 1, wherein the proton-donating organic compound is an organic compound having an alcoholic hydroxyl group. 3. The resin composition for medical equipment according to claim 1, wherein the proton-donating organic compound is an organic compound having an amine group.