JPS6158446B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to improvements in pharmaceutical compositions for external use, particularly for poultices and patches. External preparations, particularly anti-inflammatory and analgesic poultices and patches, generally contain active ingredients such as capsaicin, nonylic acid vanillylamide, methyl salicylate, monoethylene glycol salicylate, tocopherol, and diphenhydramine. These active ingredients are unstable because they contain phenolic hydroxyl groups, ester bonds, and/or amide bonds, and many commercially available anti-inflammatory and analgesic topical preparations lose their original efficacy after being stored for about 2 to 3 years. It is often not possible to obtain it. Furthermore, some of the above-mentioned active ingredients have a strong chemical odor, and it has been reported that patients are reluctant to use them. As a result of repeated research aimed at improving the stability of the above-mentioned active ingredients over time and making them odorless, the present inventors have found that when thiourea and urea are added to a pharmaceutical composition for skin application containing the above-mentioned active ingredients, We found that the problems were solved all at once. The present invention was completed based on this knowledge, and provides a dermatologically applied drug containing at least one selected from vanillylamide nonylate, monoethylene glycol salicylate, tocopherol, and diphenhydramine and a pharmaceutically acceptable base. The present invention relates to a pharmaceutical composition for external application by incorporating thiourea and urea in the composition. It is essential that the pharmaceutical composition of the present invention contains both thiourea and urea, and the mixing ratio of the two varies depending on the drug used, but in general, 0.1 to 10 parts by weight of urea to 1 part by weight of thiourea. , preferably 0.3~
It is 5 parts by weight. The total amount of thiourea and urea blended into the pharmaceutical composition of the present invention varies depending on the drug, but is 0.0005 to 50% by weight. The pharmaceutically acceptable base used in the present invention may be any base used in the production of skin-applying agents, and the following are listed as preferred examples. Poultice bases (eg carrion, bentonite, titanium oxide, zinc oxide, talc, wax, vaseline, boric acid, aluminum silicate, etc.). Adhesive water-containing patch base (for example, sodium alginate, polyacrylic resin, polyvinylpyrrolidone, polyvinyl alcohol, gum tragacanth, gum arabic, carboxymethyl cellulose, gelatin, etc.). Adhesive anhydrous patch base (for example, one mainly composed of rubber and/or synthetic resin (for example, silicone rubber, polyisobutylene rubber, acrylic copolymer, polyvinyl alkyl ether compound, etc.)) In the pharmaceutical composition of the present invention In addition, softeners such as liquid paraffin, animal oil, vegetable oil, and polybutene,
Moisturizing agents such as glycerin, propylene glycol, polyethylene glycol, sorbitol, and aluminum acetate, fillers such as red iron oxide and calcium carbonate, antioxidants, and the like may be added. The pharmaceutical composition of the present invention is prepared by kneading each component using, for example, a stirrer and crusher, a twin-screw kneader, an Ajihomo mixer, a high-torque stirrer, or a kneader, and is generally a poultice, Used as an adhesive patch. The temperature during kneading is 5°C to 130°C, preferably 10°C to 30°C for poultices, and 60°C to 120°C for adhesive patches. The preparation thus obtained may be applied to the affected area as it is, or may be spread on a known carrier (paper, woven fabric, nonwoven fabric, foamed sheet, rubber sheet, plastic film, etc.) and applied. Next, examples of the present invention will be shown, and % in the text refers to % by weight.
means. Example 1 Active ingredient composition 2.5% Monoethylene glycol salicylate 30% l-menthol 30% dl-camphor 35% α-dl-tocopherol 5% urea 8.0% thiourea 4.0% kaolin 10.0% talc 35.5% Water: 33.0% Glycerin: 7.0% The above ingredients were put into a stirrer and stirred for 40 minutes to form a paste, which was then taken out and a pharmaceutical composition for compresses was obtained. The thus obtained pharmaceutical composition for poultice has almost no chemical odor, and the poultice can be bottled for 40 minutes.
After storage for 3 months at ℃ and 60% humidity, the content of active ingredients decreased due to monoethylene glycol salicylate.
6.5%, and α-dl-tocopherol was 3.4%. On the other hand, the poultice obtained by removing urea and thiourea from the above formulation has a strong chemical odor, and after storing it under the same conditions as above, the content of active ingredients decreases by 17.9% for monoethylene glycol salicylate, α−
dl-tocopherol was 15.6%. Example 2 1 Active ingredient composition 8.5% Monoethylene glycol salicylate 63.6% l-menthol 26.4% α-dl-tocopherol 1.3% diphenhydramine 1.7% nonylic acid vanillylamide 0.2% Auronicum extract 6.8% 2 Urea, Thiourea mixture 11.5% Urea 55% Thiourea 45% 3 Styrene-isobutylene-styrene block copolymer 30% 4 Beeswax 3% 5 Olive oil 4% 6 Petroleum resin 38% 7 Water 4.5% 8 Sorbitan monoolein 0.5% Mixture numbers 3, 4, and 5 are melted and kneaded in a twin-screw kneader at 120°C. Next, add 2, 6, and 8 and keep at the same temperature for 20 minutes.
Knead for minutes, lower the temperature to 70℃, then add 1 and 5.
Add 7 and knead for 20 minutes to obtain a sticky pharmaceutical composition. This adhesive composition was spread and applied to a thickness of 0.2 mm on a nonwoven fabric at 75°C. This drug surface was covered with a polyester film. On the other hand, an adhesive pharmaceutical composition was obtained by removing urea and thiourea from the formulation of Example 2, and similarly spread on a nonwoven fabric and covered with a polyethylene film (comparative example). When applied to the skin, the formulation of Example 2 had almost no odor and its therapeutic effect was observed for 8 to 10 hours, whereas the formulation of Comparative Example had a strong chemical odor and its therapeutic effect was observed for only 4 to 5 hours. Nakatsuta. In addition, the plasters of Example 2 and Comparative Example were bottled for 40
Table 1 shows the decrease in the content of each active ingredient after storage for 3 months at ℃ and 60% humidity. 【table】

Claims (1)

[Claims] 1. A pharmaceutical composition for skin application containing at least one selected from nonylic acid vanillylamide, monoethylene glycol salicylate, tocopherol, and diphenhydramine and a pharmaceutically acceptable base, characterized in that thiourea and urea are blended. A pharmaceutical composition for external skin application.