JPH0634819B2 - Manufacturing method of molded products with excellent biocompatibility - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing a molded article having excellent biocompatibility.
More specifically, the present invention relates to a method for producing a molded article in which an ethylene-vinyl alcohol polymer (hereinafter abbreviated as EVA) layer having excellent biocompatibility is formed on the surface of the molded article.

[Prior Art] Many studies have been made on materials having excellent biocompatibility and are still vigorously advanced. For example, a thrombolytic agent such as heparin or a thrombolytic agent material such as urokinase is immobilized on a polymer, and heparin or urokinase or the like is gradually released to form no thrombus, or the formed thrombus is removed. Has been.
In polyurethane-based polymers, etc., hydrophobic and hydrophilic segments are also microphase-separated into lamellas of several hundred liters (Toshiyuki Uryu “Industrial Materials” 33 (10), 45 (1985)). ).

Furthermore, when an EVA hollow fiber membrane obtained by wet-molding a dimethyl sulfoxide solution of EVA consisting of a hydrophilic portion and a hydrophobic portion is used as an artificial kidney for extracorporeal blood circulation, heparin etc. in the blood is prevented. It has been found that dialysis can be performed smoothly without causing clogging due to thrombus formation without administration of a drug (Hidemune Naito et al., "Artificial Organs" 11
(1), 3 (1982)).

[Problems to be solved by the invention]

In the case of immobilizing heparin, urokinase, etc. on a polymer, unstable physiologically active substances must be dealt with in various respects, and the effective period for preventing thrombus is limited. Further, in the case of a polyurethane-based molded product having a lamellar microphase-separated structure, the synthesis of the polymer is complicated, and strict molding conditions must be taken to obtain the microphase-separated structure, and reproducibility is obtained. Is difficult.

The excellent antithrombogenicity of the hollow fiber membrane obtained by wet-molding a solution of EVA in dimethylsulfoxide is extremely surprising in that the polymer itself and the molding method are simple. However, as described above, the molding method is a wet molding method, and a very limited molded product can be obtained by the wet molding method. In addition, since a molded product made of EVA alone has a range of physical properties such as strength, elasticity, and flexibility,
Only practical for limited moldings.

As a method for improving the biocompatibility of various molded articles, a method of contacting a molded article with a solution of EVA dissolved in a polar solvent such as dimethylsulfoxide or N-methylpyrrolidone is also conceivable. Since it has a high boiling point, it takes a long time to evaporate at room temperature and atmospheric pressure, it is not practical, the molded product itself will be damaged when evaporating at high temperature, and uneven evaporation tends to occur when evaporating at reduced pressure The operation is also troublesome. Furthermore, since these polar solvents have high viscosities, it is difficult to perform uniform surface modification.

Therefore, an object of the present invention is to provide a method for producing a molded article having excellent biocompatibility without the above-mentioned problems.

[Means for solving problems]

Molded products that require excellent biocompatibility include, for example, catheters that require appropriate hardness and kink resistance, circuit tubes for extracorporeal circulation that require flexibility, artificial blood vessels that require the same rheological properties as blood vessels, and complex There are filters in a blood circuit having various shapes, and these are molded from materials having physical properties according to various purposes. Most of these are used in combination to form one system, and in this case, the biocompatibility of the whole system is dominated by the least biocompatible molding. Therefore, there is a need to increase the level of biocompatibility of all moldings.

In view of the above points, the inventors of the present invention mold each material by using the most rational method for the material most suitable for each purpose, and modify the surface in contact with body fluid so as to have excellent biocompatibility. Focusing on that it is possible to improve the biocompatibility of a molded product of any material and in any shape, and earnestly studied to make at least the body fluid contact surface of the molded product excellent in biocompatibility, and arrived at the present invention. . That is, the present invention is characterized in that a solution of EVA in hexafluoro-2-propanol is contacted with a molded article, and then hexafluoro-2-propanol is removed to form an EVA layer on the surface of the molded article. Is a method for producing a molded article having excellent biocompatibility.

The characteristic feature of the present invention is that a solvent that dissolves EVA having biocompatibility well and that is easily removed is found. Hexafluoro-2-propanol is a solvent that best expresses the above features. Is.

EVA used in the present invention is a copolymer of ethylene and vinyl alcohol, which has an extremely simple composition and has no problem in reproducibility and handleability. Most commonly, such a copolymer is produced by copolymerizing ethylene and vinyl acetate and then saponifying the obtained ethylene-vinyl acetate copolymer.
Copolymerization ratio of ethylene / vinyl alcohol is usually 90 / 10-1
The range of 0/90 (molar ratio) is preferable, and the range of 60/40 to 20/80 is more preferable because the antithrombotic property is further excellent. In addition to ethylene and vinyl alcohol, an ester unit such as vinyl acetate, an ionic unit such as itaconic acid or acrylic acid, vinylpyrrolidone or the like may be used as long as it does not exceed the antithrombotic property of EVA, for example, 20 mol% or less. It may contain a hydrophilic unit or the like.

As a molded product, it is less harmful to living organisms, and E on the surface
The material and shape are not particularly limited as long as the VA layer can be formed. For example, polyvinyl chloride, silicone rubber,
Endotracheal tube made of polyethylene, polypropylene, EVA, polyurethane, etc., circuit tube, artificial blood vessel, cannula, shunt, transfusion, blood transfusion tube,
Examples thereof include surgical sutures, artificial trachea, blood conduits, that is, blood circulation circuits such as artificial heart lungs and artificial kidneys, materials for auxiliary circulation devices of the heart, blood bags, artificial ureters, ligatures, and balloons.

In the method for producing a molded article of the present invention, the above EVA is dissolved in hexafluoro-2-propanol and the molded article is treated with the E
It may be brought into contact with the VA solution. The concentration of EVA solution is 0.1
It is practical to set the content to 20% by weight in order to carry out the method of the present invention, but it is preferably 1 to 10% by weight in order to more uniformly modify the surface of the molded product.

The method for bringing the molded product into contact with the solution is not particularly limited as long as the surface of the molded product can be sufficiently wetted with the above EVA solution, and an ordinary dipping method, spray method or the like can be used. In addition, an EVA layer may be formed inside a molded article such as a tube by a method of circulating the solution in the tube.

Next, it is necessary to remove the solvent hexafluoro-2-propanol as a solvent by contacting the molded product with an EVA solution to wet it, and the evaporation method is generally used as a solvent removal method. The evaporation may be carried out at a high temperature or under reduced pressure, but in the method of the present invention, a solvent that easily evaporates is used, and it is only necessary to simply perform natural drying or blast drying without using such a means. In addition, in order to make the amount of the solution adhered to be uniform before the evaporation, for example, it is free to perform centrifugal deliquoring by shaking or rotating.

The thickness of the EVA layer formed on the surface of the molded article is not particularly limited as long as the function as a medical material is not impaired, but 0.01 to 10 μm is suitable for practical use.

[Action]

According to the method of the present invention, the EVA layer can be extremely easily formed on the surface of the molded product. The reason for this is not clear, but hexafluoro-2-propanol is different from dimethylsulfoxide and the like in that it has a hydrogen donating property.
The solvent is a solvent that dissolves VA, and since the solvent has a low surface tension, the surface of the molded product is easily wetted when the molded product is brought into contact with a solution in which EVA is dissolved, and the solvent is easily evaporated. Therefore, it is considered that the EVA layer is likely to be efficiently formed on the surface of the molded product.

Hereinafter, the production method of the present invention will be specifically described with reference to Examples.

〔Example〕

Example 1 Eval F (manufactured by Kuraray Co., Ltd.) in which ethylene / vinyl alcohol was 33/67 (molar ratio) was dissolved in hexafluoro-2-propanol (manufactured by Central Glass Co., Ltd.) to prepare a 5 wt% solution. A PET mesh filter used for extracorporeal circulation of blood was dipped in this EVA solution, sufficiently wetted, lifted, gently shaken twice to drain, and then air-dried.

When the obtained mesh filter was observed with a magnifying glass, it was found that EVA was coated almost uniformly and transparently on all the portions.

In the hemodialysis of dogs that do not use an anticoagulant with EVA hollow fiber module, if a normal mesh filter is used, blood clots at the mesh filter part in the blood circuit, so that hemodialysis cannot be performed smoothly. By using the modified mesh filter obtained in the above step, hemodialysis could be performed smoothly without coagulation for 5 hours.

Comparative Example 1 A mesh filter was treated in the same manner as in Example 1 except that dimethyl sulfoxide was used as the solvent. When the obtained mesh filter was observed with a magnifying glass,
There was unevenness in the EVA adhesion amount and white spot-like abnormal parts were observed, and a good coat could not be obtained.

〔The invention's effect〕

By the method of the present invention, the surface of various molded articles for medical use is EVA.
Can be modified with. Therefore, it is possible to easily obtain a material having excellent biocompatibility that does not form a thrombus even if the antithrombotic agent is not used at all, or even if it is used less than half of the usual amount, and the industrial utility is extremely great.

Claims (1)

[Claims] 1. A solution of an ethylene-vinyl alcohol-based polymer dissolved in hexafluoro-2-propanol is brought into contact with a molded product, and then hexafluoro-2-propanol is removed to remove ethylene-vinyl alcohol on the surface of the molded product. A method for producing a molded article having excellent biocompatibility, which comprises forming a layer of a base polymer.