JPS6045220B2 - hydrogel - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a hydrogel formed by swelling a polymeric material with water.

Polymers of hydroxyl group-containing methacrylic esters and acrylic esters (hereinafter collectively referred to as hydrophilic acrylic esters), such as hydroxyethyl methacrylate, hydroxyethyl acrylate, hydroxypropyl methacrylate, and hydroxypropyl acrylate, are hydrophilic. It has good biocompatibility when absorbing water, and is used in medical devices such as ophthalmology such as soft contact lenses, dental materials such as denture bases, catheters, and materials for implantation in living organisms.

However, since these hydrophilic acrylic acid ester polymers have relatively low mechanical strength when water is absorbed, caution is often required when using them, which has been a practical difficulty.

It has been known to copolymerize bifunctional monomers such as ethylene glycol dimethacrylate in order to improve mechanical strength when water is absorbed, but in this case, the water absorption rate decreases at the same time as the strength increases. This is undesirable because it significantly impairs the properties of the polymer as a hydrophilic resin, and improvements have been desired. The present inventors have conducted extensive studies with the aim of improving the mechanical strength of the hydrophilic resin when it absorbs water without sacrificing its properties of being flexible and having good affinity for living organisms. As a result, by adding a bisepoxide compound during the polymerization of hydrophilic acrylic acid esters, the water absorption rate is the same as when copolymerizing conventionally known bifunctional monomers. We have discovered that it is possible to obtain a hydrogel with significantly improved mechanical strength when hydrated, and have arrived at the present invention.

That is, the present invention relates to the general formula CH2-go--9-σ-R
2-0H [However, R1 is hydrogen or a methyl group, R2 is an alkylene group or 1" which can have a polar group as a substituent.
4""""1"""2""7" group (however, n is 1 or more)
? A hydrogel obtained by adding a bisepoxide compound to a compound represented by the above integer (R3 is hydrogen or a methyl group) and polymerizing the resulting copolymer, which contains 10% by weight or more of water. It is.

Examples of the hydrophilic acrylic esters represented by the above general formula used in the present invention include hydroxyethyl methacrylate, hydroxyethyl acrylate, hydroxypropyl methacrylate, hydroxypropyl acrylate, glyceryl methacrylate, glyceryl acrylate, polyethylene glycol methacrylate, and polyethylene Examples include glycol acrylate, polypropylene glycol methacrylate, polypropylene glycol acrylate, 2-aminohydroxypropyl methacrylate, and 2-aminohydroxypropyl acrylate.

Therefore, in the above general formula, the polar group of R2 includes a hydroxyl group, an amino group, etc.
The group n is often 1 to 30.

In the present invention, the bisepoxide compound is a compound having a polymerizable double bond at one or both ends by bonding with the hydroxyl group of the monomer through a ring-opening reaction of the epoxy group simultaneously with the polymerization of the hydrophilic acrylic ester. But at the same time,
It also reacts with the hydroxyl groups newly generated by the ring opening of the epoxy group, resulting in a three-dimensional epoxy resin type high molecular weight product.

At this time, the unpolymerized monomer of the hydrophilic acrylic acid ester plays the role of a swelling agent for this epoxy resin type high molecular weight product, and conversely, this unpolymerized monomer serves as a swelling agent for the epoxy resin type high molecular weight product. Since it polymerizes while being incorporated into the three-dimensional network structure, there is no phase separation. In particular, if a glycidyl ether type compound obtained by the reaction of a diol compound and epichlorohydrin is used as the bis-epoxide compound, this bis-epoxide compound will dissolve well in the hydrophilic acrylic acid ester monomer and will form a polymer. Since the compatibility after treatment is good, the polymerized product exhibits good transparency and a relatively small decrease in water absorption. However, adding a large amount of bis-epoxide leads to a decrease in water absorption and an increase in Young's modulus, so it must be used in an amount of 0.1 to 2 parts by weight per 10 parts of the hydrophilic acrylic ester. .
As mentioned above, the bisepoxide compound used in the present invention is particularly preferably glycidyl ether type 7, such as bisphenol A bisglycidyl ether, ethylene glycol bisglycidyl ether, polyethylene glycol bisglycidyl ether, glycerin bisglycidyl ether, etc. Ether, propylene glycol bisglycidyl ether, polypropylene glycol bisglycidyl ether, neopentyl glycol bisglycidyl ether, 1,6-hexanediol bisglycidyl ether, hydrogenated bisphenol A5'. Examples include currant cidyl ether.

However, bisepoxide compounds other than the glycidyl ether type, such as vinylcyclohexene dioxide and dicyclopentadiene dioxide, can also be used. As the polymerization initiator, common radical polymerization initiators such as azobisisobutyronitrile, diisopropyl peroxydicarbonate, t-butyl peroctoate, potassium persulfate, etc. are used.

Polymerization methods include placing these compounds in a mold and heating them to take out the molded product, or immersing the molded product in a mixture or solution of these compounds and then taking it out and polymerizing it by heating or irradiation to coat it. There are methods to create layers. The former method is suitable for manufacturing molded products such as soft contact lenses, and the latter method is suitable for coating the surfaces of catheters and the like. Note that a small amount of a bifunctional monomer such as ethylene glycol dimethacrylate may be added as a crosslinking agent during polymerization. In this case, if the amount added is too large, the effect of adding the bisepoxide compound will be diminished and the water absorption rate will be significantly lowered, so it is preferable to use 0.5 phr or less relative to the hydrophilic acrylic ester. Also,
As a ring-opening catalyst for epoxy groups, about 10 phr of tertiary amines may be added to the bisepoxide compound. The tertiary amines used at this time are preferably those having a tertiary amine group as a substituent for the polymerizable monomer, such as dimethylaminoethyl methacrylate, in order to prevent elution from the product after polymerization. As described above, the hydrogel of the present invention can be obtained by adding a bisepoxide compound to the hydrophilic acrylic ester represented by the above general formula and polymerizing the resulting copolymer, which is then swollen by water absorption.

By the way, is the hydrogel referred to here at equilibrium swelling? Water rate (
wet weight basis) is 10% by weight or more, preferably 2% by weight or more. Compared to the conventional case where a difunctional monomer such as ethylene glycol dimethacrylate is used as a crosslinking agent, the hydrogel of the present invention has almost the same water absorption rate and greatly improves the strength when water is absorbed. Furthermore, it is transparent when water is absorbed, and does not deteriorate or devitrify even when boiled. Therefore,
Since the drawbacks of conventional hydrogels made of hydrophilic acrylic resin have been greatly improved, soft contact lenses,
It is effective as a medical material such as catheters, ophthalmological or dental prostheses, intrauterine contraceptive devices, and in-vivo implant materials.
In the present invention, other hydrophilic monomers (for example, acrylamide, acrylic acid, methacrylamide, methacrylic acid, etc.), hydrophobic monomers ( For example, it is possible to obtain a hydrogel by copolymerizing alkyl methacrylates such as methyl methacrylate, propyl methacrylate, and lauryl methacrylate, acrylonitrile, and vinyl esters to an extent that does not impede biocompatibility. Of course, embodiments are also included in the present invention.

Examples will be described below, but these examples do not limit the scope of the present invention.

Example 1 0.0 parts of polyethylene glycol bisglycidyl ether (molecular weight 400) was added to 100 parts of hydroxyethyl methacrylate (containing 0.3 parts of ethylene glycol dimethacrylate). ♀ part, dimethylaminoethyl methacrylate 0.05 part, t-butyl peroctoate 0. W
Pour between glass plates and heat at 50°C.
The thickness is 0.37077 after polymerization in northern time! A transparent film was obtained.

After boiling this film in water for 2 days and reaching equilibrium swelling, its performance as a hydrogel was determined to be 42% water absorption.
, the underwater tensile strength was 62 kg/al. Furthermore, this film was transparent even when hydrated and had no optical distortion. 0 more
．． No devitrification or decrease in strength was observed even after repeating 200 cycles of boiling 4 times in 9% saline and cooling once for 2 hours. Comparative Example 1 A transparent film was prepared in the same manner as in Example 1 by adding 0.1 part of t-butyl peroctoate to 100 parts of hydroxyethyl methacrylate (containing 0.3 parts of ethylene glycol dimethacrylate). The tensile strength in water was 6 kg/Clt.

Comparative Example 2 100 parts of hydroxyethyl methacrylate (including 6.53 parts of ethylene glycol dimethacrylate) was mixed with 0.00 parts of t-butyl peroctoate. When a transparent film was made in the same manner as in Example 1 by adding W part, the water absorption rate was 42%,
The underwater tensile strength was 32k9/Crl.

As described above, the resin of the present invention was found to have significantly improved underwater tensile strength when used as a base material for hydrogels at the same water absorption rate, compared to when crosslinked with ethylene glycol dimethacrylate. It will be done.

Example 2 100 parts of hydroxyethyl methacrylate (including 0.34 parts of ethylene glycol dimethacrylate), 0.8 parts of bisphenol A bisglycidyl ether, and 70 parts of dimethylaminoethyl methacrylate.

By adding 0.08 parts of t-butyl peroctoate and 0.1 part of t-butyl peroctoate and polymerizing in the same manner as in Example 1, a film having a water absorption rate of 35% and an underwater tensile strength of 86 k9/d was obtained.

Example 3 A mixture having the same composition as in Example 1 was placed in a casting plate made of a Teflon plate with a thickness of 8 mm with a circular hole of 14 wL in diameter, and polymerized under the same conditions as in Example 1 to form a cylindrical shape. A polymer molded product was obtained.

This was cut using a lathe for contact lens manufacturing.
Swell with 9% saline solution, diameter 14Tmm, thickness 0.2?
, a soft contact lens with a base curve of 8.6z was created. The water absorption rate and underwater tensile strength of this soft contact lens are the same as those of Example 1, and the refractive index (n?0
) is 1.444, light transmittance is 98.7% (580 order)
, the oxygen permeability coefficient in water is 5.3×10-10cc (S
'IP)・C7TL/d・Sec●CTrLHg. Example 4 Hydroxyethyl methacrylate (ethylene glycol dimethacrylate 0
．． 27 parts), 1 part of poly(hydroxyethyl methacrylate), 2 parts of bisphenol A bisglycidyl ether, and 0.1 part of azobisisobutyronitrile were added and dissolved, and the surface was etched in advance with sodium naphthalene. A Teflon intravenous indwelling cannula was immersed in this, air-dried, and then heated at 800° C. for two hours to form a surface coating layer.

Claims (1)

[Claims] 1 General formula ▲ Numerical formula, chemical formula, table, etc. ▼ [However, R_1 is hydrogen or a methyl group, R_2 is an alkylene group that can have a polar group as a substituent, or ▲ Numerical formula, chemical formula,
There are tables, etc.▼Groups (where n is an integer greater than or equal to 1, R_
3 is hydrogen or a methyl group)] 0.0 parts by weight of the bisepoxide compound
A hydrogel obtained by adding 1 to 2 parts by weight and polymerizing a copolymer containing 10% by weight or more of water.