CS241266B1 - Material for the production of medical aids - Google Patents

Abstract

Material for the production of medical devices and equipment intended especially for single use, characterized in that it contains terpolymers of ethylene with vinyl alcohol (I) and/or with vinyl alcohol derivatives of the general formula (II) and (III) where the groups Rj and Ró are hydrogen or alkyl of 1 to 12 carbon atoms, and the ethylene content is in the range of 40 to 99.8 wt. percent, with suitable comonomers being, in addition to (I), in particular vinyl formal, vinyl butyrate, vinyl acetate and vinyl etherate.

Description

The invention relates to the use of copolymers of ethylene with vinyl alcohol and its derivatives for the production of medical devices and equipment, implants, and parts that come into long-term contact with blood or physiological fluids.

The materials known so far used in healthcare are subject to increased demands for health safety and specific physical and mechanical properties corresponding to the conditions of use. In particular, emphasis is placed on strength, toughness, elasticity, transparency, resistance to degradation, etc. Among the commercially available polymer materials used for the production of disposable devices and devices, for example, polyvinyl chloride PVC, polyethylene PE, polypropylene PP, polymethyl methacrylate PMMA, polycarbonate PC, ethylene-acrylonitrile copolymers SAN, acrylonitrile-butadiene-styrene ABS, etc. Silicones and Teflon are used for some demanding long-term implants. Styrene polymers and copolymers can be applied only in those places of medical devices where the residual content of monomeric styrene is not a problem, which is usually around 0.1 to 0.2% for acrylonitrile-butadiene-styrene and styrene-acrylonitrile. It has been proven that only low-molecular polymers and copolymers derived from highly toxic monomers, such as acrylonitrile and eth-cyanoacrylic acid esters, have harmful effects, and can be applied without difficulty even for devices and appliances that come into contact with living tissues and blood, provided that a sufficient reduction in the content of low-molecular components in the polymer material is ensured.

A disadvantage of vinyl chloride-based polymers is that they require a significant addition of plasticizers for processing. For example, a soft polyvinyl chloride blend used for the manufacture of hoses and plastic bags for storing blood for transfusion services and other uses contains 25 to 50 percent by weight of dioctyl phthalate (DOP) as a plasticizer. It has been shown that a certain proportion of the PPE elutes into the cellular components of the blood. Furthermore, these blends must be very carefully

- 2,241,266 to monitor the residual content of monomeric vinyl chloride, because it has been shown that a concentration of more than 10 ppm of vinyl chloride is dangerous due to the formation of cancer. It is also known to use gels based on polyvinyl alcohol and hydraethyl methacrylates for the production of breast prostheses. However, this application had to be abandoned due to the gradual deterioration in the subsequent changes in the mechanical properties of the implants. Polyethylene and its copolymers with vinyl acetate have been used for the construction of intrauterine bodies, or as long-term drug dispensers. Also known are the claims according to US patents 4,016,251 and 4,052,505, where polyethylene and copolymers of ethylene with vinyl acetate are used either for the construction of intrauterine bodies, or as long-term drug dispensers. However, these applications are limited by the relatively low concentration of vinyl acetate in the copolymer, which has satisfactory mechanical properties and allows diffusion transport of the aforementioned drugs through the polymer layer. For example, according to US Patent No. 4,016,251, an EVA copolymer containing 22% by weight of VAC was used as a carrier for the hormone diethylstilbesterol.

Further, according to US Patent No. 4,052,505, the hormone progesterone is placed in a tube with a diameter of approximately 4 bh and further 1.5 om, which is made of an EVA copolymer containing 28 weight percent VAC.

It has now been found that the above-mentioned shortcomings are eliminated by a material for the production of medical devices and apparatus intended in particular for single-use, the essence of which lies in the fact that it is a copolymer of ethylene with vinyl alcohol (i) and/or with vinyl alcohol derivatives. of the general formula II and III

I - ... ^CH 2 - CH 1 OH * · · · II - CH ₂ - CH ~ · · · m - ... - CH ₂ - CH - ... 0 OH " ^R 1 0 - CO - R^ 0 from where groups R^ and R^ are hydrogen, or alkyl and 1 up to 12 carbon atoms.

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Particularly suitable comonomers are vinyl alcohol, vinyl formal, vinyl butyral, vinyl acetate and vinyl ethereal. The ethylene content in the copolymer is in the range of 40 to 99.8 weight percent.

The copolymers of the present invention are formed by the triad "( ^A )x-( ^B )y"(c) _w - or by the multicomponents -(á) _x (B) _y -(C) _w -.

However, it is essential that one of the components of the copolymer is ethylene (for example monomer a) and its proportion in the polymer product is within the described limits of 40 to 99.8 percent by weight. Polar components (for example monomers B, C to I) are contained in the copolymer in weight fractions, the sum of which is 0.2 to 60 percent by weight. The ethylene copolymers mentioned can be used for medical applications individually or as mixtures and composites, with the average content of the copolymer components corresponding to the described values.

The main advantage of using copolymers of ethylene with polar vinyl monomers according to the definition given in this invention is that, depending on the content of the polar monomer, it is possible to vary the elongation and elasticity of the products within a wide range and at the same time those surface characteristics that affect the clotting or non-coagulation of blood and/or the absorption of specific proteins from physiological fluids at the interphase interface of the polymer product and thus optimally control the conditions of application of the product.

When choosing the content and composition of the comonomer with a higher content of -OH and -O-CH3 -O- groups (in the range of up to 10 weight percent), the products have good surface wettability and improved blood compatibility (antithrombogenic properties).

The technology of material processing by injection molding, extrusion, rolling or pressing allows the formation of the above-mentioned ethylene copolymers into the shape of hoses, films and the production of complex shapes of moldings, which can be further connected by gluing or high-frequency or ultrasonic welding. It is of great importance that the monomer residues, possibly contained in trace amounts in commercially available semi-finished products (in granules and the like), are non-toxic and can only exceptionally and to a small extent cause a pyrogenic reaction in the organism.

The following are examples of embodiments of the invention:

- 4 Example 1:

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The terpolymer containing 70% by weight of ethyl alcohol, 0.2% by weight of vinyl alcohol and 29.0% by weight of vinyl acetate was processed by extrusion at temperatures of 150 to 220°C into tubes and films with a thickness of 0.8 mm. By welding, bags for continuous peritoneal dialysis CAPD, for infusion solutions and the like were made from the above products.

Example 2:

A copolymer containing 40% by weight of vinyl alcohol, 5% by weight of vinyl acetate and 55% by weight of ethylene was obtained by saponification of the commercially available material Lewapren (which is an ethylene-vinyl acetate copolymer containing 45% by weight of vinyl acetate, a product of BASF, NSR) in a mixture of methanol and 4-methyl acetate under the catalysis of potassium methanolate. By processing the granulate containing 0.2% of the stabilizer Nonox VDS (which is a tetraalkyl-methylene-bisphenol, a product of ICI, England) and 0.1% of a paraffinic lubricant with a relative molecular weight of 350 daltons, hoses and films suitable especially for pumping, blood storage and transfusion services are prepared.

Example 3>:

The bodies were pressed from a mixture of:

copolymer ethylene + methacrylic acid + magnesium acrylate (in molar ratio 99.5:3:2 75 wt.

copolymer ethylene + vinyl butyral + vinyl stearate (in the molar ratio 142:78:1 25 wt.

paraffin oil 0.1 wt.

stabilizer 0.1 wt.%

In the implantation experiments, the samples were placed in the subcutaneous tissue of the abdominal and thoracic parts of rabbits and rats. All test results showed positive histological evaluation of the tissue surrounding the implanted bodies after 1 month.

The material's technical properties were suitable for the construction of moving parts of the blood pump and for replacing cardiac activity.

Claims (1)

SUBJECT OF THE INVENTION Material for the manufacture of disposable medical devices and devices, characterized in that it contains terpolymers of ethylene and wool alcohol (i) and / or wool wool alcohol derivatives of the general formula (II) and (U1) ...- CH ₂ - CH ₂ ... (I) ² t OH CH, - · · · CH - R _x (II) ...- ^CH 2 - CH (m) O - CO wherein R ^ and R ^ are hydrogen or alkyl of 1 to 12 carbon atoms and the ethylene content lies between 40 and 99-8% by weight, suitable comonomers in addition to (i) being in particular vinyl formal, vinyl butyral, vinyl acetate and vinyl stearate.