JPH03258716A - Liquid agent containing azulene derivative - Google Patents

Abstract

PURPOSE:To obtain the subject liquid agent useful as an external drug such as eye drop in safe and clear state by adding glycyrrhizic acid and its salt to a system containing a specific cationic surfactant, chlorhexidines and azulene derivative. CONSTITUTION:The turbidity of a liquid agent is eliminated by adding glycyrrhizic acid and its salt to a system containing one or more substances selected from a quaternary ammonium-based cationic surfactant (e.g. benzalkonium chloride) and chlorhexidines and an azulene derivative. The amount of the quaternary ammonium-based cationic surfactant is 0.0025-0.02wt.% (based on the total liquid agent), that of the chlorhexidines is 0.001-0.02wt.% and that of glycyrrhizic acid and its salt is >=0.05wt.%, preferably >=0.1wt.%.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a liquid agent containing an azulene derivative, and more particularly, to a liquid agent containing an azulene derivative and one or more substances selected from quaternary ammonium cationic surfactants and chlorhexidines. The present invention relates to a method for eliminating cloudiness that occurs in a system containing the same, and a liquid preparation that eliminates the cloudiness.

Conventional technology Traditionally, azulene derivatives have been frequently used in cosmetics, pharmaceuticals, quasi-drugs, etc. as medicinal ingredients with anti-inflammatory, tissue-repairing, and anti-allergic effects. Cationic surfactants or chlorhexidines are frequently used as effective preservatives. However, when a quaternary ammonium cationic surfactant or chlorhexidine is added to a solution containing an azulene derivative, a cloudy phenomenon occurs.

In order to eliminate such cloudiness, a method of adding a nonionic surfactant (Japanese Patent Publication No. 1-27060) has been proposed.

Problems to be Solved by the Invention Nonionic surfactants used as solubilizing agents are generally substances with excellent solubilizing ability, but there are concerns about side effects such as hemolysis and mucosal irritation when used repeatedly. Ru.

Furthermore, it has the disadvantage of reducing the antibacterial activity of the preservative or rendering it inactive.

Means for Solving the Problems The present inventors have made intensive studies to eliminate the clouding phenomenon that occurs in systems containing azulene derivatives and quaternary ammonium cationic surfactants or chlorhexidines. They discovered that the system can be clarified by adding glycyrrhizic acid or its salt, and completed the present invention.

That is, the present invention provides a method for eliminating cloudiness in a liquid preparation, which is characterized by adding glycyrrhizic acid or a salt thereof to a system containing a 4R ammonium cationic surfactant, one or more substances selected from chlorhexidine, and an azulene derivative. The present invention also provides a liquid preparation containing one or more substances selected from a quaternary ammonium cationic surfactant and chlorhexidine, an azulene derivative, and glycyrrhizic acid or a salt thereof.

The present invention will be explained in detail below.

In the present invention, azulene derivatives include 1,4-dimethyl-7-ethyl azulene-3-sulfonic acid, 1,4-dimethyl-7-dimethyl azulene-3-sulfonic acid, 1,
4-dimethyl-7-itubrovir azulene-3-sulfonic acid and the like may be used, and salts thereof may also be used.

Further, as the quaternary ammonium cationic surfactant, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, etc. can be used.

Chlorhexidine may be a free base or a salt of chlorhexidine, and the salts include chlorhexidine gluconate, chlorhexidine gluconate,
Chlorhexidine hydrochloride and the like can be used.

As glycyrrhizic acid or its salt, glycyrrhizic acid, dipotassium glycyrrhizinate, disodium glycyrrhizinate, monoammonium glycyrrhizinate, etc. can be used.

Note that the azulene derivatives, chlorhexidines, and salts of glycyrrhizic acid may be any pharmaceutically acceptable water-soluble salts.

The amount of the quaternary ammonium cationic surfactant is 0.0025 to 0.02% by weight based on the total amount of the liquid, and the amount of chlorhexidine is 0.001 to 0.001% by weight based on the total amount of the liquid.
0.02% by weight, the amount of glycyrrhizic acid or its salt is 0.05% by weight or more based on the total amount of the liquid, preferably 0.
．． It is 1% by weight or more.

The liquid preparation of the present invention can be used as eye drops, mouth wash, armpit odor odor, etc.
Examples include external preparations such as anti-inflammatory agents, hair growth agents, and medicated cosmetics.

In the present invention, in addition to the above-mentioned essential ingredients, components normally used in the preparation of the above-mentioned preparations can be blended in the usual amounts.

For example, decongestants (naphazoline hydrochloride, tetrahydrozoline hydrochloride, phenylephrine hydrochloride, etc.), anti-inflammatory and astringent agents (
Neostigmine methyl sulfate, ε-aminocaproic acid, allantoin, berberine chloride, zinc sulfate, lysozyme chloride, etc.), antihistamines (diphenhydramine hydrochloride,
inthibenzyl hydrochloride, chlorpheniramine maleate, etc.), vitamins [vitamin A and its esters (e.g. acetate ester, valmitate ester), active vitamin Bu, vitamin B1, vitamin 13+z, vitamin E and its esters (e.g. acetate ester) ), amino acids (canium L-aspartate, magnesium L-aspartate, aminoethylsulfonic acid, sodium chondroitin sulfate, etc.), sulfa drugs, fungicides (
alcohols (glycerin, 1,3-butylene glycol, propylene glycol, ethanol, etc.), local anesthetics (lidocaine, lidocaine hydrochloride, propylene hydrochloride, dibucaine hydrochloride, etc.), Cooling agents (fl-menthol, borneol, camphor, pepper oil, etc.),
Isotonic agents (sodium chloride, potassium chloride, etc.), polymer additives (polyethylene glyco-L, polyvinyl alcohol, polyvinylpyrrolidone, hydroxyethylcellulose, hydroxybupyrmethylcellulose, etc.), stabilizers (ethylenediaminetetraacetate, etc.) , buffering agents (boric acid, housha, citric acid, sodium citrate, etc.)
, pigments (Blue No. 1, Yellow No. 5, etc.), fragrances (peppermint, etc.), and other quasi-drug ingredients that are approved in the above-mentioned preparations (e.g., 1989 Pharmaceutical Manufacturing Guidelines, edited by Japan Compendium Association). (described on pages 470 to 472) can be blended.

The liquid preparation of the present invention is prepared by dissolving each component in purified water (sterilized purified water if necessary). In addition, if the application is for eye drops, the prepared liquid must be sterilized (e.g., by sterilization or filtration). 6 Effects of the Invention The present invention eliminates the need to add a nonionic surfactant, which improves safety. It has become possible to provide clear liquid preparations.

EXAMPLES Hereinafter, the present invention will be explained in more detail with reference to Examples and Test Examples.

(Example 1) Ingredient blending amount (mg/100d) Sodium 1.4-dimethyl-7-itubrobil azulene-3-sulfonate Dipotassium glycyrrhizinate Sodium chloride Sodium boric acid Borate Benzalkonium chloride 0 50 00 000 Appropriate amount 0 Add and dissolve each of the above ingredients in sterilized purified water and dilute the total amount to 100-
and sterile filtered to prepare eye drops.

(Example 2) component Chlorpheniramine maleate Aminoethyl sulfonic acid Dipotassium glitinolate Blend amount (mg/100m5) 0 000 50 1,4-dimethyl-7-dimethyla Sodium threne-3-sulfonate Boric acid Housha sodium chloride benzethonium chloride 0 50 Appropriate amount 00 7.5 Eye drops were prepared in the same manner as in Example 1.

(Example 3) Ingredients Amount (mg/
100me) 1.4-Dimethyl-7-itubrovir azulene-3-sulfonate sodium 10 monoammonium glycyrrhizinate 150 boric acid
500 Hoshiya
Appropriate amount of sodium chloride
100 Sodium edetate
10 Chlorhexidine gluconate
5 (Example 4) Ingredients Amount (rng/
LQO-) 1.4-dimethyl-7-itubrovir azulene-3-sulfonic acid sodium 5-dipotassium glycyrrhizinate 100 ethyl alcohol 51-menthol
8゜'J Roux 1>Acid'Z Lorhexicine 1 Fragrance Trace amount Add each of the above ingredients to purified water and dissolve to make a total volume of 1o.

-, and an enemy-containing agent was prepared.

Claims (2)

[Claims] (1) A method for eliminating cloudiness in a liquid preparation, which comprises adding glycyrrhizic acid or a salt thereof to a system containing an azulene derivative and one or more substances selected from quaternary ammonium cationic surfactants and chlorhexidines. . (2) A liquid agent containing one or more substances selected from a quaternary ammonium cationic surfactant and chlorhexidine, an azulene derivative, and glycyrrhizic acid or a salt thereof.