JPS5823411B2 - 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.

More specifically, the equilibrium water content obtained by crosslinking a composition of polyvinyl alcohol (hereinafter abbreviated as PVA)-based hydrophilic polymer and albumin is high (biocompatibility, particularly blood compatibility, and mechanical The present invention relates to a hydrogel with good mechanical strength and excellent transparency.

Conventionally, hydrophilic polymer materials such as hydroxyalkyl (meth)acrylate polymers such as poly-2-hydroxyethyl (meth)acrylate, cellulose, and Kolaken have been known as materials for medical equipment. is,
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.
It has the advantage of causing less discomfort, foreign body sensation, or pain when it comes into contact with living tissue.

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-penzalkonium chloride-heparin.

On the other hand, polymers having hydroxyl groups such as PVA, ethylene-vinyl alcohol copolymers, cellulose derivatives such as cellulose and hydroxyethylcellulose, and (co)polymers of hydroxyalkyl acrylates or methacrylates such as 2-hydroxyethyl methacrylate. Heparin is 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, causing blood clots. It doesn't, but once it's dissolved, blood clots easily.

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, a joint venture, No5e et al. (Trans, Ayn.

Soc, Artificial Int-Org, 1
There is a blend composition obtained by dispersing albumin or gelatin in natural rubber latex, Vol. 7, p. 6, 1971).

The present inventors have investigated various ways to improve the anticoagulant properties of hydrogel systems with good biocompatibility without using heparin, and as a result, we have developed a blend composition obtained by blending PVA, a typical hydrophilic polymer, with albumin. The present inventors have discovered that crosslinked and insolubilized products exhibit superior properties not seen in uncrosslinked blend compositions or crosslinked and insolubilized products of PVA or albumin alone, and have completed the present invention.

That is, by blending PVA and albumin 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 there is no elution of the constituent components when used in a water-containing state. Moreover, a transparent hydrogel with good 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 hydrophilicity. 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.

As a method for crosslinking and insolubilization, (1) a method in which a blend of PVA polymer and albumin is mixed with an appropriate amount of polyvalent aldehyde having two or more aldehyde groups in the molecule and treated with acid at the same time as film formation or after film formation; , (2) Albumin and PV
Crosslinking using a polyvalent aldehyde is preferred, such as a method in which a mixture consisting of dialdehyde A is treated with an acid at the same time as film formation or after film formation.

The polyvalent aldehyde used in (1) and 2) is PV.
PVA obtained by decomposing A by periodic acid treatment etc.
In addition to dialdehydes, for (1), dialdehydes such as glyoxal, glutaraldehyde, and terephthalaldehyde, and polyhydric aldehydes such as oxidized starch and 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 elution of either albumin or PVA.

The term "hydrogel" as used herein means a polymer material having a water content of 40% or more as expressed by the following equation in equilibrium swelling of a polymeric material that has absorbed water.

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 The present invention will be specifically explained below using Examples and Comparative Examples, but the present invention is not limited by these in any way.

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

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

The properties of the hydrogel film at room temperature and in a water-containing system were as shown in Table 1.

As is clear from this table, the hydrogel film of the present invention has a higher water content than poly-(2-hydroxyethyl methacrylate), which is well-known as a medical polymer, has excellent strength, and has good film transparency. It can be seen that it is.

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
00 PVA dialdehyde (4.5% concentration) aqueous solution and albumin (3% concentration) aqueous solution are mixed at a predetermined ratio,
Hydrogel membranes were obtained in the same manner as in Examples 1-3.

The properties of this film are shown in Table 2.

As is clear from the above table, PVA~PVA dialdehyde~
It can be seen that the albumin system has a much higher water content and strength than the PVA dialdehyde-albumin system.

Example 8 The hydrogel films obtained in Examples 1 to 3 and Comparative Examples 4 to 5 were thoroughly washed with physiological saline, and 0.25 rul of dog ACD blood was placed on them in a thermostatic bath at 37°C. 0.025 ml of CaCl2 aqueous solution with a concentration of 0.1 molar
was added to initiate blood clotting.

The weight of the clot taken out after 10 minutes was compared with the clot on glass and medical silicone rubber sheets determined in the same manner, and the results shown in Table 3 were obtained.

It is clear from this table that the hydrogel membrane obtained according to the present invention has excellent anticoagulant properties.

Claims (1)

[Claims] 1. A medical hydrogel obtained by crosslinking a composition of a polyvinyl alcohol-based hydrophilic polymer and albumin using a polyhydric aldehyde and containing 40% by weight or more of water.