JPS59183762A - New anti-thromolytic material - 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 novel antithrombotic materials, and more particularly to:
After activating the surface of a polymeric material such as nylon or polyester by plasma claw discharge treatment, mucopolysaccharide is bound to the surface.It has excellent antithrombotic properties and biocompatibility, and has good mechanical strength for medical use. It relates to polymeric phase materials.

In recent years, many polymeric materials have come into use as medical H materials, and these are used in medical materials that come into direct contact with blood, such as artificial blood vessels, vascular catheters, artificial kidney tubes, heart-lung machines, and blood. When used as bypass tubes, artificial heart pumping chambers, balloon pumping materials, etc., it not only has antithrombotic properties, but also
It is necessary to have excellent mechanical strength such as biocompatibility, elasticity, durability, and wet toughness.

Among the polymer materials currently used as medical materials, for example, nylon, polyester, polyethylene, polypropylene, and polyurethane do not have antithrombotic properties.
When these polymer materials are used in places where they come into direct contact with blood, the blood coagulates and thrombi are formed, so efforts have been made to make these polymeric materials have antithrombotic properties.

Conventionally, methods for imparting antithrombotic properties to the above-mentioned polymeric materials include methods of making the material itself less likely to cause thrombotic ligation, such as mixing a natural anticoagulant such as heparin into the material or chemically bonding it to the material. Furthermore, methods of coating the surface of collagen-containing materials with excellent biocompatibility are known.

Among the above-mentioned methods, examples of methods to make the material itself less likely to cause thrombus are to use a certain kind of polyrafukun compound with a structure in which hydrophobic and hydrophilic parts alternately appear on the surface, or Some include hydrogels or hydrophilic polymers attached to a base polymer. However, although these polymeric materials exhibit fairly high antithrombotic properties,
It is still insufficient for practical use, and nothing satisfactory has yet been obtained.

In addition, as an example of a method for chemically bonding a natural anticoagulant such as Heparin to a material, after polymerizing Kekraft, a vinyl compound with a tertiary amine group, in the base polymer, Methods are known in which amino groups are quaternized and then heparinized. however,
The polymeric material heparinized in this manner has the disadvantage that the desirable mechanical strength inherent in the base polymer is reduced, making it impossible to obtain the strength and durability required for practical use.

In addition, as an example of a method for coating the surface of collagen Kl material, the surface of polyethylene, polypropylene, polyester, etc. is made hydrophilic by polarization treatment such as chromic acid mixture treatment or alkali treatment, and then collagen is applied. Next, a method of coating the collagen by irradiating radiation (Japanese Patent Publication No. 4 F'i-3743
3), or a method in which the surface of a silicone rubber moon is made hydrophilic by polarization treatment such as plasma glow discharge treatment or chemical treatment, and then coated with collagen in the same manner as described above (% Kosho 49-4559) Public bulletin) has been proposed. However, although the polymer material coated with collagen in this manner does not reduce the desirable mechanical strength inherent to the base polymer, it is not necessarily satisfactory in terms of antithrombotic properties.

In view of these circumstances, the present inventors have overcome all the drawbacks of conventional antithrombotic polymer materials, and have developed a high-quality polymer material that has excellent pile thrombogenicity and biocompatibility, and has good mechanical strength. As a result of intensive research to provide all molecular materials, we focused on the fact that mucopolysaccharide has extremely excellent antithrombotic properties and biocompatibility. We have discovered that the object can be achieved by bonding to a polymeric material whose surface has been activated by plasma glow discharge treatment, and based on this knowledge, we have completed the present invention.

That is, the present invention provides an antithrombotic material in which mucopolysaccharide is fully bound to the surface of a polymeric material activated by plasma glow discharge treatment.

Examples of polymeric materials used in the present invention include nylon, polyester, polyethylene, polypropylene,
Preferred examples include hydrophobic polymer compounds with excellent mechanical properties such as polyurethane and silicone rubber.

Mucopolysaccharides used in the present invention include, for example, evachondroitin sulfate, hyaluronic acid, heparin, and chitosan, which have extremely excellent antithrombotic properties and biocompatibility. This is clear from the fact that the surface of blood vessels of living organisms containing these mucopolysaccharides has excellent antithrombotic properties and biocompatibility.

In the present invention, in order to firmly bond the mucopolysaccharide to the surface of the polymeric material, it is necessary to activate the surface by plasma glow discharge treatment. This plasma claw discharge treatment is carried out by cleaning the surface of the polymer phase material according to a conventional method, and then uniformly applying plasma generated by a plasma claw discharge generator to the surface of the polymer material. This treatment activates the surface of the polymer, giving it the property of strongly binding to negatively charged mucopolysaccharides.

As a method for fully bonding mucopolysaccharide to the surface of a polymeric material activated by such plasma glow discharge treatment, for example, a total mucopolysaccharide aqueous solution with a concentration of 01 to 10% by weight (the concentration depends on the molecular weight of the mucopolysaccharide) is used. When coating the surface of the polymeric material, immersing the entire polymeric material in an aqueous mucopolysaccharide solution, or bonding it to the inner surface of a container or tube, the aqueous mucopolysaccharide solution is applied to the surface of the polymeric material. After the mucopolysaccharide is bonded to the surface of the polymeric material by injecting and discharging the mucopolysaccharide, the free mucopolysaccharide is removed by washing with water or physiological saline, and then air-dried or vacuum-dried at room temperature. This method is used.

The antithrombotic material of the present invention thus obtained has excellent antithrombotic properties and biocompatibility, and has good mechanical performance, and is suitable for use in various devices used in areas that come into direct contact with blood. It is extremely valuable as a gift.

Next, the present invention will be explained in more detail with reference to Examples.

Example 1 The surface of a nylon sheet was washed with acetone, washed again with hot water, and then air-dried to clean the surface.

Plasma generated from a plasma claw discharge generator is applied to this cleaned surface. During the discharge, operate so that the plasma hits the entire surface as uniformly as possible]
Discharge was performed by an inductive coupling method using 3.56 MHz radio waves. The discharge voltage was 25W, and the plasma was lit. The surface of the nylon sheet was activated by this plasma glow discharge treatment, and became in a state where it could be strongly bonded to the mucopolysaccharide having a negative charge.

Next, 0, which contained 10 parts by weight of chondroitin sulfate,
In 1.5N normal saline solution (pH=7.3)
The material was soaked in water at 20° C. for 10 minutes, washed with water, and then air-dried to obtain an antithrombotic material.

In order to investigate the surface structure of the antithrombotic material thus obtained, an infrared difference spectrum was determined by internal multiple total reflection Fourier transform infrared absorption spectroscopy. The result is shown in Figure 1 f.

In Fig. 1, A is a nylon sheet treated with plasma glow discharge as described above, coated with collagen, pH adjusted and chondroitin sulfate added, and B is a nylon sheet treated with collagen as described above. This is an antithrombotic material obtained by As is clear from this figure, A and B basically have the same spectra, and it can be seen that the surface of the antithrombotic material of the present invention is coated with chondroitin sulfate.

Next, the antithrombotic material obtained above was added to a solution of plasma protein albumin dissolved in total physiological saline.
After immersing at ℃ for 10 minutes, it was air-dried, and the structure of the adsorbed albumin was investigated by obtaining an infrared difference spectrum in the same manner as above. (Table for comparison) Untreated nylon seams) K treated in the same way as above, infrared difference spectrum? I asked for it. These results are shown in FIG.

In FIG. 2, B is the antithrombotic material obtained in the example, and C is the treated nylon sheetra. As can be seen from this figure, the shapes of the peaks of amide ■ and amide ■, which are characteristic of proteins, are different in the case of the antithrombotic material of the present invention compared to the case of the untreated nylon sheet. This indicates that the structure of the adsorbed albumin is different.

Furthermore, in place of the albumin solution, a plasma protein fibrinogen solution was used, and the same procedures as above were performed to obtain an infrared difference spectrum.

The results are shown in Figure 3.

In FIG. 3, B and C are the same as above.

As is clear from this figure, the amount of fibrinogen adsorbed is large in the untreated nylon treated with Sheetke, and the structural change of fibrinogen is also large, but the amount of fibrinogen adsorbed is large in the untreated nylon sheet treated with the antithrombotic material of the present invention. It can be seen that there are few structural changes.

Next, in in vitro and in vitro experiments, the antithrombotic properties of the antithrombotic materials and untreated nylon sheets obtained in the examples were investigated using platelet-rich plasma from which red blood cells had been removed. Untreated nylon sheets are prone to formation of fibrin networks, deformation and adsorption of platelets, but the antithrombotic material of the present invention forms fibrin networks, causes less deformation of shattered platelets, and has a small amount of adsorption.

Example 2 A thread-like antithrombotic material was obtained in the same manner as in Example 1, except that a nylon sheet was used instead of the nylon sheet in Example 1.

In a j, n vi, vo (in vivo) experiment, the above thread-like antithrombotic material was suspended in the artery of a dog to examine its antithrombotic properties.

For comparison, antithrombotic properties of untreated nylon threads were also investigated in the same manner.

As a result, blood clots occurred with untreated nylon thread, whereas
The antithrombotic material of the present invention did not cause any thrombus formation.

[Brief explanation of the drawing]

Figures 1, 2, and 3 are infrared difference spectra obtained by internal multiple total reflection Fourier transform infrared absorption spectroscopy to investigate the surface structure of nylon sheets subjected to various treatments. Figures 2 and 3 show infrared difference spectra of the antithrombotic material of the present invention and an untreated nylon sheet treated with plasma glow discharge treatment and then sequentially coated with collagen and chondroitin sulfate. These are infrared difference spectra of albumin and fibrinogen adsorbed, respectively. -11- Fig. 1 fL 4L (cm-'> Fig. 2 Toga (cm) Fig. 3 Shokyo (C?f+-1)

Claims (1)

[Claims], 1. An antithrombotic material comprising mucopolysaccharide fully bound to the surface of a polymeric material activated by plasma glow discharge treatment. 2. The antithrombotic material according to claim 1, wherein the polymeric material is nylon, polyester, polyethylene, polypropylene, polyurethane, or silicone rubber.