JPS5823410B2 - Hydrogel Youkizai - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a hydrogel made of a polymeric material that absorbs water and swells.

Specifically, the present invention relates to a hydrogel having a high equilibrium water content and excellent biocompatibility and mechanical properties, which is made of a crosslinked blend composition of a polyvinyl alcohol (hereinafter abbreviated as PVA) hydrophilic polymer and gelatin.

Conventionally, hydrophilic polymer materials such as hydroxyalkyl (meth)acrylate polymers such as poly-2-hydroxyethyl (meth)acrylate, cellulose, and collagen have been known and used as materials for medical equipment. They are selected and used as appropriate depending on the purpose, location, use, etc.

Medical devices using these hydrophilic polymer materials have excellent compatibility with living organisms because the materials are wet or contain water, and have the advantage of causing less discomfort, foreign body sensation, or pain when they come into contact with living tissue. have.

However, such hydrophilic polymers generally have poor mechanical properties when hydrated, and many have insufficient strength.

Furthermore, its compatibility with living organisms is not always sufficient depending on the application, and in particular, anticoagulability, which is one of the important indicators of biocompatibility for materials that come into contact with blood, is still not as good as natural materials. be.

One way to solve this problem is to use heparin, a natural anticoagulant, in combination with polymeric materials.
For example, Gott et al. [Science 142, p. 1297 (1963)] obtained an anticoagulant material by treating the surface of the material with graphite-benzalkonium chloride-heparin.

On the other hand, PVA, ethylene-vinyl alcohol copolymers, cellulose and cellulose derivatives such as hydroxyethyl cellulose, (co)polymers of hydroxyalkyl acrylates or methacrylates such as 2-hydroxyethyl methacrylate, etc. have hydroxyl groups. Polymers are often used in a swollen state with water, blood, or body fluids, and if heparin is simply absorbed or adsorbed to the surface, the heparin will dissolve into the blood in a short period of time, and during that time, it will not clot. Although it does not cause blood clots, it can easily cause blood clots after dissolution.

Therefore, in order to obtain a material that does not cause blood clots over a long period of time, this method requires that heparin be fixed to the material in some way.

On the other hand, as a method for improving anticoagulation that does not use heparin, a joint venture, No5e et al. [T, rans, Am, Soc, Ar
tificial Int, Org, Volume 17, Page 6 (19
71)] The present inventors have explored various ways to improve the anticoagulant properties of a biocompatible hydrogel system without using heparin. As a result, the cross-linked and insolubilized Brent discharge material obtained by blending PVA, a typical hydrophilic polymer, with gelatin was found to be mixed with an uncrosslinked blend composition or a cross-linked and insolubilized product of PVA alone or gelatin alone. The present invention was completed based on the discovery that this material exhibits excellent properties that cannot be avoided.

That is, by blending PVA and gelatin according to the method of the present invention and insolubilizing it by the method described below, it has a high water content and good mechanical properties, and when used in a water-containing state, the constituent components A transparent hydrogel with no elution and excellent biocompatibility can be obtained.

The hydrophilic polyvinyl alcohol polymer used in the present invention includes completely saponified and partially saponified vinyl ester homopolymers, as well as a small proportion of other vinyl monomers within the range that does not impair water solubility. Includes vinyl alcohol copolymers containing units.

In all cases, the polymerization degree used is 500 or more, and the saponification degree is 80% or more, preferably 98% or more.

Methods for crosslinking and insolubilization include (1) a method of mixing an appropriate amount of polyhydric aldehydes having two or more aldehyde groups in the molecule with a PVA polymerized motoseratin blend and treating with an acid; (2) a method of mixing gelatin and PVA dimethyl Crosslinking using a polyvalent aldehyde is preferred, such as a method in which aldehyde is blended in the presence of an acid without the coexistence of PVA.

As the polyhydric aldehyde used in (1) and (2), P
PV obtained by decomposing VA by periodic acid treatment etc.
In addition to dialdehyde A, for (1), dialdehydes such as glyoxal, glutaraldehyde, and terephthalaldehyde, oxidized starch, and polyvalent aldehydes such as acrolein polymers and copolymers are used.

When the crosslinked product thus obtained is immersed in water, it absorbs water and forms a transparent hydrogel without any elution of gelatin or PVA.

Hydrokel as used herein refers to a polymer material that has absorbed water and has a water content of 40% or more as expressed by the following equation at the time of equilibrium swelling.

The hydrogel of the present invention has good compatibility with living organisms and is used for molded products that come into contact with blood and living tissues, specifically dialysis membranes and hollow fibers in the fields of artificial blood vessels, artificial lungs, and artificial kidneys. It is used in (hollow fiber) type dialysis membranes, activated carbon coating materials for adsorption artificial kidneys, artificial skins, contact lenses, coating materials for tablets, microcapsules, carriers for therapeutic drugs or enzymes, etc.

In addition to medical use, it is also expected to be used as a separation membrane for industrial and analytical purposes.

EXAMPLES Hereinafter, the present invention will be specifically explained with reference to Examples, but these Examples are not intended to limit the present invention in any way.

Examples 1 to 3 A PVA (6% concentration) aqueous solution, a gelatin (3% concentration) aqueous solution, and a glutaraldehyde (25% concentration) aqueous solution were mixed at a predetermined ratio, and this solution was adjusted to pH 1 with an IN-hydrochloric acid aqueous solution.

This polymer solution was cast onto glass, air-dried at room temperature for 2 days, and then immersed in water and peeled off to obtain a hydrogel film made of a cross-linked PVA-gelatin blend.

The properties of this hydrogel film in a water-containing system at room temperature were as follows.

Examples 4 to 7 PVA (6% concentration) aqueous solution, commercially available PVA (polymerization degree 170
Molecular weight 66 obtained by treating 0) with sodium periodate
A PVA dialdehyde (4.5% concentration) aqueous solution and a gelatin (3% concentration) aqueous solution of No. 00 were mixed at a predetermined ratio, and a hydrogel film was obtained in the same manner as in Examples 1 to 3.

The properties of this film are shown in the table below.

Example 8 The hydrogel films obtained in Examples 1 to 3 and Comparative Example 4 were thoroughly washed with physiological saline and placed in a constant temperature bath at 37°C.
Dog ACD blood was placed on the plate at a rate of 0.25 r/'Ll, and 0.025 ml of 0.1M CaCl2 aqueous solution was added thereon to initiate clotting.

The weight of the clot taken out after 10 minutes was compared with the weight of clot on glass and medical silicone rubber sheets determined in the same manner, and the results were as shown in the following table.

Claims (1)

[Claims] 1. A medical hydrogel comprising a crosslinked product obtained by crosslinking a mixture of a polyvinyl alcohol-based hydrophilic polymer and gelatin using a polyvalent aldehyde and containing 40% by weight or more of water.