JPH10182458A - Indomethacin-containing preparation composition for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject composition capable of reducing skin irritation, which has been adverse side effects, low irritant, having high effects and useful for treating blows, etc., by formulating the composition indometacin and chlorpheniramine maleate therein. SOLUTION: This indomethacin-containing preparation composition for external use is obtained by formulating (A) 1 pt.wt. indomethacin with (B) 0.01-3.0 pts.wt. chlorpheniramine maleate. The amount of the formulated ingredient A is preferably 0.1-2.0wt.% and that of the formulated ingredient B is preferably 0.001-0.6wt.%. A lower alcohol, e.g. methanol, a dissolution auxiliary, e.g. diisopropyl adipate, a surfactant, etc., e.g. a sorbitan ester of a fatty acid may further be formulated.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an indomethacin-containing external preparation composition that causes little skin irritation when applied or affixed to the skin.

[0002]

2. Description of the Related Art An external preparation containing indomethacin, an anti-inflammatory drug, has been used as one of the remedies for pain caused by bruises, sprains, muscle fatigue, and pain associated with stiff shoulders. These were useful in terms of the potent anti-inflammatory action of indomethacin and reduction of side effects of systemic action by local administration. However, even if topical indomethacin is applied, if the percutaneous absorption of indomethacin is increased to a certain level or more by an absorption enhancer or the like, the effect is enhanced, but there is a problem in terms of skin irritation which is a side effect in external use. Could occur. In general, glycyrrhetinic acid and its salts have been incorporated into skin irritation caused by drugs, but it has been difficult to say that the effect is sufficient.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to solve the disadvantages of the prior art and to provide an indomethacin-containing external preparation which is less irritating and highly effective when applied or affixed to the skin. It is in.

[0004]

Means for Solving the Problems As a result of studies, the present inventors have found that by adding chlorpheniramine maleate to an external preparation containing indomethacin, skin irritation, which is a side effect of external application of indomethacin itself, can be prevented. The present inventors have found that this can be reduced and completed the present invention. That is,
The present invention is an external preparation composition containing indomethacin and chlorpheniramine maleate.

In the present invention, the amount of indomethacin compounded is 0.1 to 2 in the composition (in the case of an aerosol, in the undiluted solution).
0% by weight is preferred, and the blending amount of chlorpheniramine maleate is preferably 0.001 to 6.0% by weight. If the amount of indomethacin is less than 0.1% by weight, the medicinal properties of indomethacin itself cannot be expected, and if it exceeds 2.0% by weight, the yellow color of indomethacin increases,
It is not suitable for external application because it may contaminate clothes. When the amount of chlorpheniramine maleate is less than 0.001% by weight, the effect of the present invention is weakened,
When the content exceeds 6.0% by weight, side effects of chlorpheniramine maleate itself begin to appear.

Further, in the present invention, indomethacin and chlorpheniramine maleate are simultaneously formulated to exhibit an effect, so that the blending ratio thereof is important. That is, the mixing ratio is preferably in the range of 0.01 to 3.0 parts by weight of chlorpheniramine maleate with respect to 1 part by weight of indomethacin. Indomethacin 1
If the compounding ratio of chlorpheniramine maleate is less than 0.01 part by weight, the effect of the present invention is difficult to obtain, and if it exceeds 3.0 parts by weight, chlorpheniramine maleate is in excess. Therefore, it is uneconomical.

[0007] Dosage forms that can achieve the effects of the present invention include liquids, creams, ointments, gels, patches, aerosols, and the like. Absent.

In the external preparation composition of the present invention, water, lower alcohols (methanol, ethanol, denatured ethanol, isopropyl alcohol, etc.) and solubilizers (diisopropyl adipate, isopropyl myristate, 1,3-butylene) may be used, if necessary. Glycol, propylene glycol, polyethylene glycol, glycerin, medium-chain fatty acid triglycerides, fatty acid esters, various vegetable oils, various animal oils, polyhydric alcohol fatty acid esters, alkyl glyceryl ethers, hydrocarbons, lactic acid, sodium hydroxide, etc.), surfactants (Sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester,
Propylene glycol fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbite fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene alkyl ether,
Polyoxyethylene alkyl phenyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, polyoxyethylene beeswax derivative, polyoxyethylene lanolin derivative, polyoxyethylene alkylamide, polyoxyethylene alkylamine, lecithin derivative, polymer emulsifier Etc.), emulsion stabilizers (higher alcohols, etc.), gelling agents (polymers, etc.), adhesives, etc., and other commonly used base components for obtaining a desired dosage form can be compounded. Are vasodilators (carpronium chloride, benzyl nicotinate, assembly extract, panax ginseng extract, vitamin E acetate, pepper tincture, etc.), corticosteroids (hydrocortisone acetate, hydrocortisone butyrate propionate, etc.), keratolytic agents (urea, salicylic acid, etc.) Humectants (sodium hyaluronate, chondroitin sulfate, Cordyceps sinensis extract, saffron extract, etc.), fungicides (chlorhexidine gluconate, isopropylmethylphenol, quaternary ammonium salts, hinokitiol, etc.), antioxidants (dibutylhydroxytoluene, Isopropyl gallate, a refreshing agent (menthol, peppermint oil, camphor and the like), a fragrance, a pigment, and the like can be blended as long as the effects of the present invention are not impaired.

[0009]

Industrial Applicability According to the present invention, it has become possible to provide an indomethacin-containing external preparation which is less irritating and more effective even when applied to the skin.

[0010]

The present invention will be described more specifically with reference to the following examples and test examples.

Example 1 (External solution) (Components) (Blending amount W / v%) Indomethacin 0.75 Chlorpheniramine maleate 0.1 Diisopropyl adipate 5.00 Isopropyl myristate 3.00 Glycerin 2.00 Poly Oxyethylene alkyl ether 3.00 Denatured ethanol 45.00 Purified water Total 100 ml The above components were stirred and uniformly dissolved to obtain a liquid preparation for external use.

Example 2 (External Cream) (Components) (W%) Indomethacin 1.0 Chlorpheniramine maleate 0.5 Medium-chain fatty acid triglyceride 20.0 Diisopropyl adipate 5.0 Propylene glycol 12.0 Polyoxyethylene sorbitan monostearate 6.0 Sorbitan monostearate 3.0 Glycerin monostearate 8.0 Purified water Total 100 g Using the above components, an external cream was produced by a conventional method.

Example 3 (gel) (Components) (Blending amount W%) Indomethacin 0.5 Chlorpheniramine maleate 0.01 Polyethylene glycol monostearate 5.0 Diisopropyl adipate 3.0 1,3-butylene Glycol 8.0 Polyvinylpyrrolidone 0.5 Carboxyvinyl polymer 1.5 Diisopropanolamine Appropriate amount Denatured ethanol 30.0 Purified water Total 100 g Using the above components, a gel for external use was produced by a conventional method.

Example 4 (Patch) (Ingredient) (Blending amount W%) Indomethacin 0.5 Chlorpheniramine maleate 0.5 Polyoxyethylene sorbitan monooleate 1.0 Propylene glycol 5.0 Polyacrylic acid 7.0 Sodium polyacrylate 6.0 Silicic anhydride 1.0 Tartaric acid 0.5 Aluminum glycinate Suitable amount Aluminum hydroxide Suitable amount Purified water Total 100 g Using the above components, an external patch was produced by a conventional method.

Example 5 (Aerosol) (Component) (Blending amount W%) Indomethacin 0.4 Chlorpheniramine maleate 0.04 Polyoxyethylene sorbitan tristearate 1.2 Diisopropyl adipate 2.0 1,3 -Butylene glycol 1.2 Ethanol 20.0 Purified water 15.16 Isopentane 10.0 Liquefied petroleum gas 3.0 Dimethyl ether 47.0 Using the above components, an external aerosol was produced by a conventional method.

Comparative Example 1 (External solution) An external solution was prepared in the same manner as in Example 1 except that chlorpheniramine maleate was omitted from the formulation of Example 1. Comparative Example 2 (External solution): Chlorpheniramine maleate was removed from Example 1 and glycyrrhetinic acid was replaced by 0.3.
An external preparation was prepared in the same manner as in Example 1 except that w / v% was added. Comparative Example 3 (External solution): An external solution was prepared in the same manner as in Example 1 except that indomethacin and chlorpheniramine maleate were removed from Example 1.

[0017]

[Test Example] 10 µl of each of the external preparations prepared in Example 1 and Comparative Examples 1 to 3 was applied to a patch test patch (mini-size: Torii Pharmaceutical Co., Ltd .; hereinafter referred to as “Patch Bond”). Time, obstruction was applied. At this time, an uncoated patch bond as a blank was similarly closed and applied for 24 hours. Twenty-four hours later, peel off the patch bond and visually determine the stimulus,
Immediately after. After 1 hour, 3 hours, 5 hours,
After 24 hours, the same determination was made. The visual evaluation was scored as 0 for no reaction, 1 for faint erythema and 2 for clear erythema. The results are shown in Tables 1 to 7.

[0018]

[Table 1]

[0019]

[Table 2]

[0020]

[Table 3]

[0021]

[Table 4]

[0022]

[Table 5]

[0023]

[Table 6]

[0024]

[Table 7]

From the results shown in Tables 1 to 7, the external preparation prepared in Example 1 clearly reduced the skin irritation of indomethacin, and showed almost the same results as those of Comparative Example 3 and blank where no indomethacin was added. . Further, from Comparative Example 2 in which glycyrrhetinic acid, which is widely used as an inhibitor of skin irritation, was added, it was found that Example 1 had a high effect of suppressing indomethacin-derived irritation. Therefore, it was confirmed that the present invention is a hypoallergenic indomethacin-containing external composition.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 47/22 A61K 47/22 E

Claims (3)

[Claims] 1. An external preparation composition containing indomethacin and chlorpheniramine maleate. 2. The external preparation composition according to claim 1, wherein the compounding ratio of chlorpheniramine maleate is 0.01 to 3.0 parts by weight per 1 part by weight of indomethacin. 3. The compounding amount of indomethacin is 0.1-2.
0% by weight, and the compounding amount of chlorpheniramine maleate is 0.001 to 6.0% by weight.
The external preparation composition according to the above.