JPH02264723A - antifungal agent - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to an antifungal agent, and more particularly to an antifungal agent in which the transdermal absorption of minonazole nitrate is enhanced.

PRIOR ART Mi':1nazole nitrate has been shown to be highly effective against candidiasis and candidiasis, and is therefore used in various countries as a therapeutic agent for these diseases. As a therapeutic preparation, it was necessary to improve the penetration of the drug into the stratum corneum, since it is necessary to kill the bacteria present in the horn 7i in the case of yamakari and candidiasis.

Conventionally, there have been products containing transdermal absorption enhancers to enhance the permeability of miconazole nitrate into the horn r↓, but the effects were not sufficient.

Problems to be Solved by the Invention An object of the present invention is to provide a formulation that further enhances the permeability of miconazole nitrate into the stratum corneum and provides an excellent feeling of use.

Means to Solve the Problem The present inventors have carried out intensive research to achieve the above object, and have found that by applying to the skin a preparation containing miconazole nitrate, an aliphatic hydroxy acid or its salt, and glycols. The present invention has been completed by discovering that the synergistic effect of aliphatic human [1-oxyacid or its salt and glycols] significantly improves the permeability of miconazole nitrate into the stratum corneum.

1. That is, the present invention is an antifungal agent containing miconazole nitrate, a salt of an aliphatic F-droxy acid, and glycols.

In the present invention, aliphatic hydroxy acids include lactic acid, citric acid, malic acid, tartaric acid, and glycolic acid. Moreover, the salt of an aliphatic hydroxy acid is a salt of an aliphatic hydroxy acid and an alkali metal such as sodium or potassium.

Glycols include propylene glycol, 1,3-butylene glycol, polyethylene glycol, and the like.

In the present invention, the amount of miconazole nitrate is 0.1 to 2.0% by weight of the total amount of the preparation, the amount of aliphatic hydroxy acid or its salt is 0.05 to 4.0% by weight of the total amount of the preparation, and the amount of glycols is 0.05 to 4.0% by weight of the total amount of the preparation. The blending amount is 2.0 to 20.0% by weight of the total amount of the preparation.
It is.

In addition, the antifungal agent of the present invention may include antihistamines (e.g., diphenhydramine hydrochloride, inthibenzyl hydrochloride, etc.), antipruritic agents (e.g., crotamiton, etc.),
Anti-inflammatory agents (e.g., guttyrrhetinic acid, dipotassium glycyrrhizinate, etc.), local anesthetics (e.g., dibucaine hydrochloride, lidocaine hydrochloride, etc.), keratolytic agents (e.g., urea, dipotassium glycyrrhizate, etc.), surfactants (e.g., propylene), glyconyl monooleate, polyoxyethylene sorbicun monostearate, sorbitan monostearate, glycerin monostearate, etc.), cooling agents (e.g.
menthol, camphor, etc.), gelling agents (carboxyvinyl polymers, etc.), neutralizing agents (diisopropanol, etc.), solvents (ethyl alcohol, etc.), oil components (liquid halafine, etc.), and polymers (e.g., polyacrylic acid J
-Stell, ethyl cellulose, etc.) may be blended within a range that does not impair the effects of the present invention.

The antifungal agent of the present invention can be prepared into various types of preparations such as lotions, creams, gels, and aerosols according to commonly used methods (for example, methods specified in the 11th edition of the Japanese Pharmacopoeia). .

Effects of the Invention As a result of the present invention, the permeability of miconazole nitrate into the stratum corneum has been increased, making it possible to provide an antifungal agent with significantly enhanced bactericidal activity.

Furthermore, as a result of the increased permeability of miconazole nitrate into the stratum corneum, it has become possible to reduce the amount of miconazole nitrate compounded than in the past, which also solves the problem of its skin-widening effect.

Furthermore, the transdermal absorption enhancer in conventional antifungal agents has a problem of not being soluble in water and giving a greasy feeling when used, but the antifungal agent of the present invention has a good feeling when used.

The effect of Test Example Unreleased +17I is achieved only when an aliphatic hydroxy acid or its salt and glycols are used together, due to their synergistic effect. This cannot be obtained when used alone.

This fact will be explained below using test examples.

[Measurement of the content of miconazole nitrate in the stratum corneum (1) Preparation of test samples Samples with formulations N011 to N017 shown in Table 1 were prepared in the following manner.

Mix and dissolve miconazole nitrate, glycols, and ethyl alcohol, and mix with this solution.
A solution prepared by dissolving a oxysalt salt in purified water was poured into the solution, and the solution was stirred and dissolved to obtain a uniform test sample solution.

The sample solution for Control 1 was prepared by mixing and dissolving miconazole nitrate, propylene glyfur, ethyl alcohol, and MN (J water).The sample solution for Control 2 was prepared by mixing and dissolving miconazole nitrate and ethyl alcohol. It was prepared by mixing a solution of an aliphatic hydroxy acid salt dissolved in purified water in advance and dissolving it with stirring.

(2) Test Animal A Wistar hairless rat (male, 7 weeks old) was used, and its abdomen was hair-removed with clippers and used for the test.

(2) Measurement of intrakeratin content Test samples 1 to 7 and control samples 1 and 2 were applied in an amount of 20 mg to an area of 1.8 x 2.5 cm on the abdomen of a rat from which hair had been removed.

After leaving it as it was for 24 hours, the test sample remaining on the skin surface at the application site was sampled with a rayon cloth soaked in a 70% alcohol aqueous solution containing 8% sodium lauryl sulfate and 1% phosphoric acid. Next, apply cellophane tape to the skin surface of the application site.1. After compression, the stratum corneum was peeled off. To this end, the exfoliation of the stratum corneum was repeated 12 times with a new seven-layer cycle to completely remove all the stratum corneum. Next, this section Uj /'i >
Collect the ``r---'' and extract it with methanol and alcohol, and extract the minonazole nitrate-containing 111 in the stratum corneum with high-speed liquid extraction. It has been decided.

The results are shown in Table 2.The results are the average value of 1L for each weapon (tests were conducted 5 times).

Table 2 J〆Example The present invention will be described in detail below with reference to Examples.

Example 1 (if'l N Me 1 Nazole 0.8 heavy I^ part, Crotamiton 5 + I-c fit part, Menthol 0.5 city!■
% parts, lidocaine hydrochloride 2j'rT, fit F'M
, TI' D Hillenku') 'J-le 10.0i (
-, ni ljJ, 1゛J゛l! Reulois double layer (1 part and: I-Tyl alcohol 59.55 + 17 (1 part)
; Dissolve part i with stirring, and add citric acid and 1-liu l to this separately.
, 0.15" parts by weight, 5 parts urea (stop part and purified water 15 parts)
A solution obtained by stirring and dissolving a certain amount of Tit was added to obtain a tincture.

Example 2 Glass 19 pieces 1 Nazole 10 heavy parts, Ri [7 pieces 10 pieces
rHl'il: 1 part by weight of lidocaine hydrochloride, 1 part by weight of glycyl chloride, 1 part by weight, poly, :x: y-tongri-
111 parts of Nord 5 and 60 parts of Ethyl Runor 1
Part N, stir and dissolve 17, and carboxyvinylborin-07 city! 4 parts of sodium lactate, 1 part of sodium lactate, and 1 part of 213 parts of purified water were added and mixed. , 0.7 parts by weight of diisopropanolamine and 11 parts were added to the solution of . ,
A gel was obtained by stirring and mixing.

Example 3 Mi''-1 Nazole nitrate 1.0 parts by weight 111' parts, Schiff hydrochloric acid:
0.5 parts by weight of hydramine, 5 parts by weight of 11 tamiton, 1-3 parts by weight of brobylene glycol monooleate, 1.4 parts by weight of oxyethylene sorbicun monooleate
Heavy! 1 part, 4 parts of sorbitan monosugar.

Stir 5 parts of liquid paraffin and 10 parts of glycerin mo7nosdaleate while heating 71:;i,,
Shinoko.

In advance, dipotassium glycyrrhizinate, 0.5Ti
jU part, malic acid dithorium 02 heavy fj 1 part, 1.3-
10 parts by weight of butylene glycol, 3 parts IA of Nisder polyacrylate (aqueous J-Mulsion), and 54 parts of purified water.
A solution obtained by stirring and dissolving 11 parts of 8-fold I was added to the above solution and emulsified using a homomixer to obtain a Knome agent.

Claims (1)

[Claims] (1) An antifungal agent containing miconazole nitrate, an aliphatic hydroxy acid or a salt thereof, and glycols.