JPH0129765B2 - - Google Patents

Description

[Detailed description of the invention]

This invention relates to a cross-linked hydrogel used in a therapeutic system that is used for the purpose of removing or alleviating various disorders of the body by contacting it directly with the body surface or sealed in a container. More specifically, the purpose is to provide a crosslinked hydrogel that has good water retention properties and does not soften and deform due to increases in outside temperature in summer or body heat after being applied to the body, nor does it release water. Various water-containing materials are known as materials for treating symptoms such as bruises and sprains, and for relieving muscle stiffness. Examples include a mixture of kaolin, glycerin and an aqueous gelatin solution, or a mixture of a hygroscopic alkaline earth metal salt, polybutene, gum arabic or gelatin, polyhydric alcohol, water, kaolin and bentonite. However, since these water-containing materials have a low cohesive force and are muddy, they have various problems such as remaining on the body surface after use or becoming sticky due to plasticization due to perspiration. Recently, in order to improve such water-containing materials, crosslinkable polymers such as polyvinyl alcohol, polyacrylates, cellulose derivatives, etc. are added to the materials, and the polymers are combined with crosslinking components such as metal salts, borax, polyester, etc. Although a method of crosslinking the above-mentioned polymer using an isocyanate compound or the like has been proposed, there is still a problem that the adhesion to the skin is insufficient. The present invention solves these drawbacks and relates to a cross-linked hydrogel that has a water-retaining ability that provides a cooling or cooling effect and an adhesive property that adheres closely to the surface to which it is applied, and which is particularly effective in therapeutic systems. The present invention provides a hydrogel that exhibits the following properties. That is, this invention provides a polymer with an alkyl group having a functional group capable of reacting with an epoxy group having 4 carbon atoms.
A cross-linked product that contains the following (meth)acrylic acid alkyl ester copolymer, water, and a polyepoxide containing two or more glycidyl ether groups in its molecule as essential components, and is used in a pasted or covered state for therapeutic purposes. type hydrogel. The hydrogel of the present invention is characterized by holding a large amount of water, having good water retention and shape retention, having suitable adhesiveness, and not necessarily requiring a heating process during production. Furthermore, the feature of not requiring a heating process, for example, is that even if a hydrogel is manufactured by mixing each component so that the drug is uniformly dispersed or dissolved in the hydrogel, the drug does not decompose due to heat. It is possible to provide a crosslinked hydrogel that has an exceptional effect in that there is no loss of drug due to undesirable effects such as deterioration, volatilization, etc. Used in carrying out this invention (meta)
The acrylic ester copolymer is a water-soluble copolymer obtained by copolymerizing (meth)acrylic ester with a monomer having a functional group that can react with an epoxy group, such as a carboxyl group or a hydroxyl group, in the polymer. or a mixture of the copolymer with an optional component such as a water-soluble plasticizer having good compatibility with the copolymer and low volatility, such as a polyether polyol or a polyhydric alcohol. As a preferable example of the above (meth)acrylic acid ester copolymer, (meth)acrylic acid-(meth)
Acrylic ester copolymers and derivatives thereof,
Examples include (meth)acrylamide-acrylonitrile-(meth)acrylic acid ester copolymer and derivatives thereof. In addition, a graft polymer can also be used as the above-mentioned copolymer. It is desirable to use these (meth)acrylic acid ester copolymers in a solid content range of about 20 to 75% by weight, preferably 30 to 70% by weight of the crosslinked hydrogel. It lacks shape retention, and it is difficult to obtain sufficient adhesion or adhesion to ensure reliable application to the body surface, and if it exceeds 75% by weight, the cold retention and cooling effect will be insufficient, making it undesirable as a therapeutic system. It is. A polyepoxide as a crosslinking component that reacts with the epoxy groups in the substance to crosslink the substance is blended into the mixture of the (meth)acrylic acid ester copolymer and water to provide a crosslinked hydrogel. Examples of the polyepoxide include (poly)ethylene glycol diglycidyl ether, (poly)propylene glycol diglycidyl ether, triglycidyl isocyanurate, diglycerin triglycidyl ether, glycerin diglycidyl ether, trimethylolpropane polyglycidyl ether, and the like. One or more of these is based on the above (meth)acrylic acid ester copolymer.
It is added in a proportion of 0.05 to 5% by weight. The crosslinked hydrogel thus constituted is enclosed in a flexible bag-like material or formed on a carrier, and used in a therapeutic system for eliminating or alleviating physical disorders. In addition, when the hydrogel of this invention is used for disease treatment, which is one of the most suitable uses, a predetermined amount of active substances such as drugs according to the purpose is added at an appropriate stage of manufacturing the hydrogel. do. The crosslinked hydrogel of the present invention has excellent cold retention and cooling sensation effects, and also has good shape retention, and does not become plasticized and sticky or remain after being applied to the body. In addition, the system using drugs is
Due to the suitable properties of the hydrogel as described above, a therapeutic material is provided that ensures the delivery of the drug to the body and provides sufficient medicinal efficacy. Examples of this invention will be shown below. The words "part of the text" indicate parts by weight. Example 1 100 parts of ethyl acrylate and 30 parts of acrylic acid were polymerized in 195 parts of ethyl alcohol using 0.3 parts of potassium persulfate as a polymerization catalyst under an inert gas (polymerization temperature 60°C), and after the completion of the polymerization reaction. , and neutralized with an aqueous sodium chloride solution to obtain an ethyl acrylate-acrylic acid copolymer sodium salt as a water-soluble substance. Next, water is added to the sodium salt to make a 30% solution, and polyoxypropylated sorbitol as a water-soluble plasticizer is added to 100 parts of the solid content of this solution.
100 parts and 20 parts of triglycidyl isocyanurate
% aqueous solution is added and mixed, spread on the surface of a 100μ thick rayon nonwoven fabric to a thickness of about 1 mm, and crosslinked at room temperature to obtain a sheet-shaped crosslinked hydrogel. Example 2 90 parts of acrylic acid, 10 parts of butyl acrylate, 50 parts of polyoxypropylated sorbitol, and 2 parts of ammonium persulfate were dissolved in 350 parts of water, and polymerized at 60° C. for 8 hours in an inert gas stream. To 100 parts of the viscous solution thus obtained, 60 parts of polyoxypropylated sorbitol, 30 parts of 20% potassium hydroxide aqueous solution,
After adding 10 parts of a 10% triglycidyl isocyanurate aqueous solution and mixing uniformly, the mixture is spread on a 100 μm thick rayon nonwoven fabric to a thickness of about 1 mm to obtain a sheet-like crosslinked hydrogel. Table 1 shows the test results of Examples 1 and 2.

[Table] In Comparative Examples 1 and 2 in Table 1, the polyepoxide used as a crosslinking component used in the formulation of Examples 1 and 2 was not added. Reference example 1 includes 15 parts of gelatin, 4 parts of sodium polyacrylate (average degree of polymerization 30,000 to 66,000), 10 parts of glycerin, and water.
36 parts, methyl salicylate 2 parts, dl-camphor-2
It is a water-containing material consisting of 1 part of l-menthol and 2 parts of glycerin diglycidyl ether, and Reference Example 2 is made of sodium carboxymethyl cellulose.
4.8 parts methylcellulose 2.4 parts, sodium polyacrylate 3.8 parts, gelatin 5.9 parts, glycerin 35.6 parts.
47.5 parts of water, 1.3 parts of l-menthol, dl-camphor
It is a water-containing material consisting of 1 part of methyl salicylate, 2 parts of methyl salicylate, and 1.2 parts of thymol. Test method in Table 1 90 degree peel adhesive strength: Width 5 cm from the test gel sheet,
Take three test pieces approximately 20 cm in length, place the hydrous gel surface on a Bakelite plate whose surface has been thoroughly cleaned with ethyl alcohol, and roll an 850 g pressure roll 300 mm/
After crimping once at a speed of min. and leaving it for 30 minutes, attach the test plate to a 90 degree peeling jig. The jig was placed in the lower chuck, and one end of the test piece was placed in the upper chuck, and the pendulum of the chopper type tensile tester was set free, and the test pieces were continuously peeled off at a speed of 300 mm/min, a total of 4 times each time about 20 mm was peeled off. Read the load and find the average value. Then, the average value of the three test results is taken as the adhesive strength. Rheometer resistance value: Using the hydrogel compositions of Examples, Comparative Examples, and Reference Examples, a sheet-shaped hydrogel body having a size of approximately 6 cm square and a thickness of 10 mm is prepared for testing. This gel body was measured using a rheometer (manufactured by Fuji Rika Kogyo Co., Ltd.).
RUD-J type) placed on the lab jack installed on the test stand, and raised the lab jack so that the sample surface was in contact with the measurement terminal disk with a diameter of 10 mmφ and thickness of 3 mm attached to a rod that interlocked with the rheometer main body. Adjust the zero point. Next, after lowering the lab jack accurately by 5 mm, set the rheometer sample stage so that the rising distance is 10 mm. Next, set the recorder so that it works with the rheometer, and
The sample stage is raised at a speed of mm/min and the relationship between the stress applied to the compression ring and the measurement terminal is recorded. The stress when compressed by 5 mm on this recording paper is defined as the resistance value. Glue residue: After applying the test piece to the test subjects (10 people) for 6 hours, remove it and visually judge whether the gel remains on the skin surface. ○: No residue observed at all. △: Slight residue is observed. ×: There is a lot of residue. Warm water immersion test: Take a test piece approximately 2 cm square from the sample gel sheet, immerse it in 40°C warm water for 1 hour, and then visually judge the state of the gel. In the examples of this invention, methyl salicylate drugs are mainly shown, but other drugs include corticosteroids, antibiotics, anesthetics, antihistamines, antibacterial substances, other analgesic anti-inflammatory agents, antifungal agents, Applies to dermatological drugs such as emollients, vitamins, and antispasmodics, as well as systemic drugs such as sedatives, antimalarials, antipyretics, nerve stabilizers, antihypertensives, anticholinergic agents, and hypnotics. It is possible.

Claims (1)

[Scope of Claims] 1. A (meth) alkyl group having a functional group capable of reacting with an epoxy group in which the number of carbon atoms is 4 or less
A crosslinked hydrogel containing an acrylic acid alkyl ester copolymer, water, and a polyepoxide containing two or more glycidyl ether groups in its molecule as essential components, and is used in a patched or covered state for therapeutic purposes. 2. A cross-linked hydrogel according to claim 1, in which a drug is added to the hydrogel. 3. The crosslinked hydrogel according to any one of claims 1 to 2, which has a water content of about 15 to 80% by weight.