JPH01299564A - Antithrombotic medical molded product and manufacture thereof - 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 [Field of Industrial Application] The present invention relates to a medical molded article having excellent antithrombotic properties and a method for producing the same. More specifically, the present invention relates to an antithrombotic medical molded article whose surface is coated with a polyvinyl alcohol polymer and a method for producing the same.

[Conventional technology]

Polyvinyl alcohol has long been known as a material with excellent antithrombotic properties, and various attempts and proposals have been made for its use in medical applications. Since polyvinyl alcohol does not have high mechanical strength as it is, the range in which it can be used alone is limited, and it is generally used by coating it on a base material made of another material. Furthermore, since polyvinyl alcohol is easily soluble in water, it is often heat-treated to increase the degree of crystallinity to make it soluble in water, or to be made insolubilized by introducing cross-linking bonds. Methods for introducing cross-linking include the use of cross-linking agents and radiation irradiation, but these methods are difficult to operate and have various restrictions on application, so they are rarely used. It's not a practical method.

[Problem to be solved by the invention]

The method of heat-treating polyvinyl alcohol to increase its crystallinity and make it less soluble in water is a highly practical method because it is easy to operate. Even after heat treatment at a temperature of 0.
It did not reach 25 or higher and could not be sufficiently insolubilized. Therefore, it has not been possible to obtain a material with sufficient insolubility for practical use by this method.

Furthermore, soft polyvinyl chloride is often used in devices that come into direct contact with blood, such as blood circuits used for extracorporeal blood circulation and catheters inserted into blood vessels, but it has problems with its antithrombotic properties, and improvements need to be made. desired. Therefore, it may be possible to coat the surface of polyvinyl chloride with polyvinyl alcohol, but since polyvinyl chloride and polyvinyl alcohol do not have good adhesion, is it better to use polyvinyl alcohol?
, II may be separated. In particular, soft polyvinyl chloride is often deformed during use and is therefore susceptible to peeling.

The present invention was made to solve these problems, and its common purpose is to provide a medical molded article in which the surface of a base material is coated with a polyvinyl alcohol polymer, and to improve practicality. Our goal is to provide superior products. More specifically, the first objective is to provide a molded article coated with a polyvinyl alcohol polymer that has a high degree of crystallinity, is practically insoluble, and has excellent antithrombotic properties.

The second object is to provide a medical molded article in which a base material made of a polyvinyl chloride molded article and a polyvinyl alcohol polymer coated on the surface thereof are firmly adhered.

[Means to solve the problem]

The above-mentioned first objective is to include glycerin when coating a polyvinyl alcohol polymer on a substrate, and further to heat-treat the polymer to have a crystallinity of 0.26 to 0.0.
This is achieved by controlling the range of 32. The second object is achieved by interposing a layer made of a resin composition containing a graft copolymer of polyvinyl alcohol and vinyl chloride between the polyvinyl chloride base material and the polyvinyl alcohol polymer coating. Ru.

That is, the present invention provides a molded article whose surface is coated with a polyvinyl alcohol polymer, the polyvinyl alcohol polymer having a crystallinity of 0.26 or more. 0.32 or less, and a polyvinyl alcohol-based polymer containing glycerin is coated on the surface of the molded article, dried, and then heat treated. This is a method for producing an antithrombotic medical molded article. In addition, the invention for achieving the second object includes a layer made of a resin composition containing a graft copolymer of polyvinyl alcohol and vinyl chloride on the surface of a base material made of a polyvinyl chloride polymer,
This is an antithrombotic medical molded article characterized by being coated with a polyvinyl alcohol polymer.

[Effect]

By adding glycerin to a polyvinyl alcohol-based polymer, it is possible to easily obtain a product with a high degree of crystallinity even when heat-treated at a relatively low temperature, and the degree of crystallinity is 0.2.
If it is 6 or more, it becomes practically insoluble. Moreover, if the degree of crystallinity is 0.32 or less, it has excellent antithrombotic properties.

Furthermore, since the graft copolymer of polyvinyl alcohol and vinyl chloride has excellent affinity for both polyvinyl chloride and polyvinyl alcohol-based polymers, by interposing it between the two, polyvinyl chloride and polyvinyl Adhesion with alcohol-based polymers can be improved.

〔Example〕

The polyvinyl alcohol polymer used in the present invention is a polymer composed entirely or mostly of vinyl alcohol units, and is produced by complete or partial saponification of polyvinyl acetate. The degree of polymerization of the polymer is
1,000 or more is preferably used, and other components may be copolymerized in small amounts.

There are no particular limitations on the base material for coating the polyvinyl alcohol polymer, and examples include polyvinyl chloride, polyurethane, polyethylene, polypropylene, polyester, polyamide, polymethyl methacrylate, polycarbonate, and polyacrylonitrile.

Examples include various polymeric materials such as cellulose, cellulose ester, and natural synthetic rubber, metals, and ceramics. Among these, polyvinyl chloride is softened by adding a plasticizer and is often used in applications that come into direct contact with blood, such as blood circuits and catheters.

The method of coating the surface of the base material with the polyvinyl alcohol polymer is to immerse the base material in a solution of the polyvinyl alcohol polymer, or to apply the solution to the surface by a method such as spraying, and then to dry it. method is the most common.

If glycerin is added to the polyvinyl alcohol polymer solution at this time, a polyvinyl alcohol polymer containing glycerin can be obtained. The content of glycerin is 10% of polyvinyl alcohol polymer.
1 to 100 parts by weight relative to 0 parts by weight, 5 to 5
A range of 0 parts by weight is preferred. As a solvent for dissolving the polyvinyl alcohol polymer, water or water-soluble 8! A mixed solution with a solvent can be preferably used, and the concentration of the polyvinyl alcohol polymer is preferably in the range of 3 to 30% by weight.

After coating with the polyvinyl alcohol polymer, the degree of crystallinity can be increased by performing heat treatment. The heat treatment is preferably performed at a temperature of 50 to 150°C, and the treatment time is adjusted so that the degree of crystallinity is 0.26 or more and 0.32 or less. If the crystallinity is less than 0.26, it will be easily dissolved, which is not preferred in practice. Further, if glycerin is used, the degree of crystallinity can be increased to about 0.5 degrees, but if the degree of crystallinity exceeds 0.32 degrees, the antithrombotic properties will decrease, which is not preferable. A particularly preferred range of crystallinity is 0.27 to 0.30. Note that the degree of crystallinity here is a value X calculated from the density d of the polyvinyl alcohol layer using the following formula.

1/d = x/1.34+(1-x)/1.2
7 When polyvinyl chloride is used as the base material, it is coated in advance with a resin composition containing a graft copolymer of polyvinyl alcohol and vinyl chloride before being coated with a polyvinyl alcohol polymer. The graft copolymer can be obtained by emulsion polymerization of vinyl chloride in the presence of polyvinyl alcohol. In order to coat a polyvinyl chloride substrate, the emulsion obtained by polymerization may be applied directly or diluted to the substrate and dried. At this time, a surfactant or a polyvinyl alcohol polymer may be added to the emulsion solution. In addition, it is preferable to wash the substrate with a surfactant solution or an organic solvent before coating in order to achieve uniform coating.

If the film produced by the above method is used as is, glycerin will be eluted, so it is preferable to immerse the film in an aqueous solution or a water-soluble organic solvent to extract and remove the glycerin before using it in a living body. Removal of glycerin after heat treatment does not reduce antithrombotic properties.

The present invention will be explained in more detail below with reference to specific examples. In addition, "parts" in the examples mean "parts by weight" unless otherwise specified.

Example 1 78 parts of a 40% aqueous solution of ethanol and polyvinyl alcohol (degree of polymerization 1,750, degree of saponification 99.5 mol%) 1
3 parts of glycerin and 8.7 parts of glycerin, 100-1
The polyvinyl alcohol was dissolved by heating in an autoclave at 20°C. Next, 10 parts of this solution, 0.094 part of sodium dodecyl sulfate, and polyvinyl alcohol were added.
6.14 parts of vinyl chloride graft copolymer emulsion (manufactured by Kodai Co., Ltd.) and 1 part of a 40% aqueous solution of ethanol
A solution was prepared by mixing 6.2 parts and heating to 70't'.

The solution prepared above is applied to a soft polyvinyl chloride film that has been subjected to ultrasonic cleaning with a surfactant solution and acetone cleaning, and is dried at room temperature to form a resin containing a polyvinyl alcohol-vinyl chloride graft copolymer on the surface. A polyvinyl chloride film having a layer formed of the composition was obtained.

Next, 8.0 parts of polyvinyl alcohol (IE degree of 1) 750 degrees, degree of saponification 99.5 mol%), 2.0 parts of glycerin.
4 parts were heated and dissolved in 89.6 parts of water, and this was applied to the film obtained above and dried at room temperature. Then, heat treated at 70°C for 5 minutes, immersed in methanol for 2 days, and dried.
A polyvinyl chloride film whose surface was coated with polyvinyl alcohol was obtained. The polyvinyl alcohol layer was firmly fixed to the obtained film, and did not peel off even when the film was bent in a dry or wet state. Further, the polyvinyl alcohol layer was insoluble in water at 37°C.

Bovine γ-globulin (IgG) was treated with chloramine T at 12J.
This was added to a phosphate buffer and brought into contact with the polyvinyl alcohol coated side of the film obtained above at 37° C. for 3 hours. After that, the film was gently washed with phosphate buffer and the amount of IgG adsorbed to the film was measured using a γ-ray scintillation counter, and the amount of IgG adsorbed was 0.1) °C g/crA.
Met.

In order to determine the degree of crystallinity of the polyvinyl alcohol in the film obtained above, a polyvinyl alcohol-glycerin solution was applied on the glass surface, dried and heat treated under the same conditions to obtain polyvinyl alcohol, and then the density was measured. did. As a result, the crystallinity was 0.27.

Example 2 A polyvinyl alcohol-vinyl chloride copolymer resin composition layer was formed on a polyvinyl chloride film in the same manner as in Example 1. Next, 8.0 parts of polyvinyl alcohol and 1.6 parts of glycerin were heated and dissolved in 90.4 parts of a 40% ethanol aqueous solution, and this was applied to the film obtained above and dried at room temperature. And finally. 1) When the amount of IgG adsorption was measured after heat treatment at 0°C for 5 minutes, it was found to be 0.12°C.
g/c++! Met.

Further, when the crystallinity of polyvinyl alcohol was measured in the same manner as in Example 1, it was found to be 0.28.

Comparative Example 1 Same as Example 1 except that glycerin was not used,
When a polyvinyl alcohol film was prepared using a glass surface and the crystallinity was measured, it was 0.14 and 37
It was easily soluble in water at ℃. So, one more
) Heat treatment was performed at 0°C for 30 minutes, but the crystallinity was 0.2.
It reached only up to 2, and still dissolved about 15% in water at 37°C. Therefore, it can be seen that if glycerin is not used, it is difficult to form an insoluble polyvinyl alcohol layer under practical conditions.

In addition, 1) When the adsorption amount of IgG was measured for the material heat-treated at 0°C, it was found to be 0.13°C g/co! Met. It is said that materials with excellent antithrombotic properties have less protein adsorption, so it can be seen that the material of Example 1 is also excellent in terms of antithrombotic properties.

Comparative Example 2 A polyvinyl alcohol solution was applied directly to a polyvinyl chloride resin film in the same manner as in Example 1 except that a resin composition layer containing a graft copolymer was not formed, but the liquid was repelled and the solution was not uniformly applied. I couldn't. Also,
When the non-uniformly coated material was heat-treated under the same conditions, the polyvinyl alcohol layer on the surface easily peeled off.

Comparative Example 3 8.0 parts of polyvinyl alcohol and 1.6 parts of glycerin were heated and dissolved in 90.4 parts of water to produce the polyvinyl chloride prepared in Example 1 with a graft copolymer layer formed on the surface. It was applied onto a film and dried at room temperature. Then, heat treatment was performed at 130°C for 30 minutes, and the amount of IgG adsorbed was measured, and it was found to be 0.18°C g/cal. In addition, the crystallinity of the polyvinyl alcohol layer at this time was determined in Example 1.
When measured in the same manner as above, it was 0.36. Comparing this result with the result of Example 1, it can be seen that the amount of IgG adsorbed is large and the antithrombotic property is inferior. Thus, the degree of crystallinity and antithrombotic properties have a close relationship, and when the degree of crystallinity exceeds 0.32, the antithrombotic properties decrease.

〔Effect of the invention〕

According to the present invention, a molded article coated with a polyvinyl alcohol polymer is provided which is insoluble under normal use conditions and has excellent antithrombotic properties. Further, even when polyvinyl chloride is used as the base material, a molded article in which the polyvinyl alcohol polymer layer and the base material are firmly adhered can be obtained.

In addition, since it can be manufactured with extremely simple operations, it can be easily applied to the inner surface of tubes, etc.
Blood circuit 2 Suitable for artificial blood vessels, catheters, etc.

Claims (3)

[Claims] (1) A molded article whose surface is coated with a polyvinyl alcohol polymer, the polyvinyl alcohol polymer having a high thrombotic property characterized by having a degree of crystallinity of 0.26 or more and 0.32 or less. Medical molded products. (2) A method for producing a highly thrombotic medical molded article, which comprises applying a polyvinyl alcohol-based polymer containing glycerin to the surface of the molded article, drying it, and then heat-treating it. (3) The surface of a molded article made of a polyvinyl chloride polymer is coated with a polyvinyl alcohol polymer via a layer made of a resin composition containing a graft copolymer of polyvinyl alcohol and vinyl chloride. A highly thrombotic medical molded article characterized by: