JP2005145925A - Skin care preparation for external use and skin torpent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a skin care preparation for external use uninfluential on the function and form of a drug preparation, enabling easy formulation, having excellent safety/stability and exhibiting sufficient irritation suppressing effect. <P>SOLUTION: The skin care preparation is compounded with a benzoylaminodicarboxylic acid or a benzenesulfonylaminodicarboxylic acid both expressed by formula (I) (X<SP>1</SP>, X<SP>2</SP>and X<SP>3</SP>are each independently hydrogen atom, a 1-4C alkyl, hydroxy group, a 1-4C alkoxy, amino, a 1-4C alkylamino, a 1-4C acyl, nitro, cyano, a halogen atom or trifluoromethyl group; Y is carbonyl group or sulfonyl group; and (n) is 1 or 2) or its salt. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a skin external preparation having skin irritation relieving properties containing benzoylaminodicarboxylic acid or benzenesulfonylaminodicarboxylic acid.

  Conventionally, skin external preparations usually have groups such as water, alcohols, salts, oils and fats, waxes, hydrocarbons, higher fatty acids, higher alcohols, silicone oils, powders, surfactants, emulsifiers, gelling agents and the like. In addition to the ingredients of the ingredients, whitening agents, anti-aging agents, acne agents, astringents, rough skin inhibitors, vitamins and other agents, preservatives and UV inhibitors, pigments, fragrances, stabilizers Various functional ingredients such as are blended.

  In order to guarantee the use of the external preparation for skin, the formulation is designed to ensure safety, and can be used safely without causing irritation to the majority of people. However, in spite of such a formulation design, there are people who feel irritation to the topical skin preparation. For example, patients with lower alcohol sensitivity may feel hypersensitivity to a specific component (lower alcohol), and patients with atopic disease may feel excessive stimulation with a specific drug due to the disease.

Furthermore, a person with a skin quality generally referred to as so-called sensitive skin may feel sensitive irritation that is not felt in normal use. There are also stimuli that occur due to use on areas where the skin is sensitive, such as around the eyes, and irritation that occurs due to usage methods such as rubbing a preparation containing powder into the skin. In addition, irritation may be caused not only by the ingredients but also by the formulation system. There are also stimuli caused by the use environment such as use under severe conditions such as under strong sunlight.
As described above, in the use of the external preparation for skin, there are various causes of irritation, and various methods for alleviating / preventing irritation to the skin have been studied.

  For example, various denatured alcohols were blended or used after aging for a certain period of time in order to alleviate the stimulation of lower alcohols. However, these methods were hardly effective. On the other hand, a topical skin preparation with a reduced amount of skin irritation of lower alcohol, in which a specific amount of a hydroquinone glycoside (such as arbutin) and a lower alcohol are blended, is disclosed (Patent Document 1).

  In addition, a method for suppressing / preventing irritant and / or erythematous skin symptoms using salicin (Patent Document 2) and a method for suppressing / preventing irritant and / or erythematous skin symptoms using ferulic acid glucoside ( Patent Document 3) is disclosed. Furthermore, an alcohol stimulus mitigating agent (Patent Document 4) containing a specific glucose derivative as an active ingredient has been disclosed as a method for reducing irritation particularly for lower alcohols. In addition, an irritation mitigation method using N-lauroyl-L-glutamic acid (Patent Document 5) is also disclosed.

  However, although the external preparation for skin shown in Patent Document 1 is excellent in the stimulating and mitigating effect of lower alcohol, the problem is that the preparation is colored over time, the problem that it is affected by the pH of the system at the time of blending, and the oxidation stability The salicin shown in Patent Document 2 has a hydroxyl group at the benzylic position of the glucose binding group, and therefore has stability such as oxidation stability, light stability, and thermal stability. There is a problem.

  Furthermore, the ferulic acid glucoside disclosed in Patent Document 3 is difficult and expensive to produce, and has a problem in terms of stability of the preparation. In addition, there is a problem that cis-trans conversion of the double bond occurs and the color changes to yellow. In addition, the glucose derivative shown in Patent Document 4 is often difficult to produce and is not easy to prepare. In addition, there are problems such that the preparation is colored over time, and the stimulus mitigation effect is not sufficient.

  The N-lauroyl-L-glutamic acid shown in Patent Document 5 is used as a surfactant in cosmetics and the like, and the effect of the formulation system on the emulsified formulation etc. is large due to its surfactant activity, and also the irritation mitigating effect. There is a problem that is not enough.

  Under such circumstances, there has been a strong demand for the development of a drug that does not affect the function and form of the preparation, is easy to formulate, is excellent in safety and stability, and has a sufficient stimulating effect.

  On the other hand, cosmetics containing acylamino acids are disclosed in Patent Document 6, for example.

In addition, N-long chain acylaminodicarboxylic acid represented by the aforementioned N-lauroyl-L-glutamic acid is widely used as a surfactant, but the use other than the surfactant is described in the aforementioned Patent Document 5. It is only what has been done. Further, as other acylaminodicarboxylic acids for cosmetics, N-acetylglutamic acid listed in the formulation standard for cosmetic varieties is known.
JP-A 61-227514 Japanese Patent Laid-Open No. 10-36238 JP 10-36239 A Japanese Patent No. 3308763 Special Table 2000-517335 JP 49-85244 A

However, there are no external preparations for skin containing benzoylaminodicarboxylic acid or benzenesulfonylaminodicarboxylic acid, and nothing is known about the irritation mitigating effect of this substance. In view of such circumstances, the present inventors have conducted extensive research, and as a result, certain benzoylaminodicarboxylic acids and benzenesulfonylaminodicarboxylic acids have sufficient stimulating and mitigating effects without affecting the function and form of the preparation. It was found to have
Accordingly, an object of the present invention is to provide a skin external preparation that does not affect the function and form of the preparation, is easy to formulate, is excellent in safety and stability, and has a sufficient irritation mitigating effect.

  The present invention is a skin external preparation characterized by containing a benzoylaminodicarboxylic acid, benzenesulfonylaminodicarboxylic acid represented by the following general formula (I), or a pharmaceutically acceptable salt adduct thereof.

(In the formula, X ¹ , X ² and X ³ are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, an amino group, and 1 to 1 carbon atoms. 4 represents an alkylamino group, an acyl group having 1 to 4 carbon atoms, a nitro group, a cyano group, a halogen atom or a trifluoromethyl group, Y represents a carbonyl group or a sulfonyl group, and n represents 1 or 2. )

  According to the present invention, there is also provided a skin irritation relieving agent comprising a compound represented by the following general formula (I) and / or a pharmaceutically acceptable salt adduct thereof.

(In the formula, X ¹ , X ² and X ³ are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, an amino group, and 1 to 1 carbon atoms. 4 represents an alkylamino group, an acyl group having 1 to 4 carbon atoms, a nitro group, a cyano group, a halogen atom or a trifluoromethyl group, Y represents a carbonyl group or a sulfonyl group, and n represents 1 or 2. )

  Here, the compound represented by the general formula (I) is preferably N-benzenesulfonylglutamic acid, N-benzoylglutamic acid, N-benzenesulfonylaspartic acid or N-benzoylaspartic acid.

  Furthermore, according to the present invention, there is provided a method for alleviating skin irritation characterized by using a compound represented by the following general formula (I) and / or a pharmaceutically acceptable salt adduct thereof.

(In the formula, X ¹ , X ² and X ³ are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, an amino group, and 1 to 1 carbon atoms. 4 represents an alkylamino group, an acyl group having 1 to 4 carbon atoms, a nitro group, a cyano group, a halogen atom or a trifluoromethyl group, Y represents a carbonyl group or a sulfonyl group, and n represents 1 or 2. )

ADVANTAGE OF THE INVENTION According to this invention, the skin external preparation by which the skin irritation resulting from the irritation | stimulation substance to skin, for example, a fat-soluble chemical | medical agent (especially ultraviolet absorber) was reduced can be provided.
Moreover, the skin irritation relieving agent of the present invention is excellent in relieving skin irritation caused by substances that cause irritation to the skin.
Furthermore, according to the present invention, it is possible to provide a skin irritation mitigation method that does not affect the function and form of the preparation, is easily formulated, is excellent in safety and stability, and has a sufficient irritation mitigation effect.

Hereinafter, the present invention will be described in detail.
The benzoylaminodicarboxylic acid, benzenesulfonylaminodicarboxylic acid and pharmaceutically acceptable salt adduct thereof used in the present invention are the compounds represented by the general formula (I), optical isomers and pharmaceutically acceptable salts thereof. It is an adduct.

In X ¹ , X ² , and X ³ , the alkyl group having 1 to 4 carbon atoms represents a chained or branched alkyl group, specifically, a methyl group, an ethyl group, a propyl group, a butyl group, or an isopropyl group. , Isobutyl group, sec-butyl group, tert-butyl group and the like. The alkoxy group having 1 to 4 carbon atoms represents a linear or branched alkoxy group, and specifically includes a methoxy group, an ethoxy group, a propoxy group, a butoxy group, an isopropoxy group, an isobutoxy group, a sec-butoxy group, a tert. -Butoxy group and the like.

  The alkylamino group having 1 to 4 carbon atoms represents a linear or branched monoalkyl or dialkylamino group. In the case of a dialkyl group, the two alkyl groups independently form an alkyl group having 1 to 4 carbon atoms. You can do it. Specifically, methylamino group, dimethylamino group, ethylamino group, diethylamino group, propylamino group, butylamino group, isopropylamino group, isobutylamino group, sec-butylamino group, tert-butylamino group, N-methyl -N-ethylamino group, N-methyl-N-propylamino group, N-methyl-N-butylamino group and the like can be mentioned. The acyl group having 1 to 4 carbon atoms represents a chain-like or branched acyl group, and specifically includes an acetyl group, a propanoyl group, a butyryl group, and the like.

  Examples of the halogen group include chloro, bromo and fluoro.

In the general formula (I), X ¹ , X ² , and X ³ are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, or a hydroxyl group. Preferred is a hydrogen atom. Y represents a carbonyl group or a sulfonyl group, and a sulfonyl group is preferred. N represents an integer of 1 or 2, and 2 is preferable.

  Examples of the compound represented by the general formula (I) used in the present invention include N-benzoyl aspartic acid, N-toluyl aspartic acid, N-anisoyl aspartic acid, N-chlorobenzoyl aspartic acid, N- Fluorobenzoylaspartic acid, N-dimethylaminobenzoylaspartic acid, N- (acetylbenzoyl) aspartic acid, N-benzenesulfonylaspartic acid, N-toluenesulfonylaspartic acid, N-methoxybenzenesulfonylaspartic acid, N-chlorobenzenesulfonylaspartic acid N-fluorobenzenesulfonylaspartic acid, N-dimethylaminobenzenesulfonylaspartic acid, N-benzoylglutamic acid, N-toluylglutamic acid, N-anisoylglutamic acid, N-chloro Benzoyl glutamic acid, N-fluorobenzoyl glutamic acid, N-dimethylaminobenzoyl glutamic acid, N- (acetylbenzoyl) glutamic acid, N-benzenesulfonyl glutamic acid, N-toluenesulfonyl glutamic acid, N-methoxybenzenesulfonyl glutamic acid, N-chlorobenzenesulfonyl glutamic acid, N -Fluorobenzenesulfonyl glutamic acid, N-dimethylaminobenzenesulfonyl glutamic acid and the like.

  Among these, N-benzenesulfonyl glutamic acid, N-benzoyl glutamic acid, N-benzenesulfonyl aspartic acid or N-benzoyl aspartic acid is particularly preferable for the general formula (I).

  The compounds represented by the above general formula (I) used in the present invention include racemates and optical isomers, and diastereomers may exist depending on the substituents. However, this does not impair the effects of the present invention. Accordingly, racemates, optical isomers and, in some cases, diastereomers and / or mixtures of diastereomers, respectively, of the compound represented by the above general formula (I) are also included in the present invention. Is included.

  In addition, the compound represented by the above general formula (I) used in the present invention can form a salt adduct with a pharmaceutically acceptable base, but between the above general formula (I) and the salt adduct thereof. There should be no difference in effectiveness, but rather it should be used according to the nature of the formulation used. Examples of the pharmaceutically acceptable salt that forms a salt adduct with the compound represented by the above general formula (I) include sodium salt, potassium salt, ammonium salt, triethylammonium salt, triethanolammonium salt and the like.

  There are two types of salt adducts formed with the compound represented by the general formula (I) and a pharmaceutically acceptable base, which are mono-salts and di-salts. It can be properly used depending on the pH of the preparation. In the present invention, the salt adduct formed from the compound represented by the general formula (I) and a pharmaceutically acceptable base may be prepared in advance.

  The compound represented by the general formula (I) used in the present invention is a known substance and can be easily synthesized by a commonly used method. For example, benzoylglutamic acid can be synthesized by reacting glutamic acid and benzoyl chloride in an aqueous sodium hydroxide solution, and benzenesulfonylglutamic acid can be synthesized by reacting glutamic acid and benzenesulfonyl chloride in an aqueous sodium hydroxide solution.

  In order to obtain the compound represented by the general formula (I) used in the present invention as an optically active substance, an optically active raw material, reagent, catalyst or the like may be used, and conformational isomers and geometric isomers may be used. In the case where a isomer exists, it can be obtained as a pure conformational isomer and geometric isomer by appropriately selecting raw materials and reaction conditions and performing a separation operation. Further, when a functional group is present in the molecule and this functional group interferes with the reaction or there is a fear of the reaction, it is preferable to proceed the reaction efficiently using an appropriate protecting group. The protecting group can be used according to, for example, Protective Groups in Organic Synthesis by Theodora W. Greene and Peter G. M. Wuts.

  Although the mechanism of action of the compound represented by the above general formula (I) according to the present invention is not clear, it can be used as a skin irritation substance contained in the skin external preparation by containing it in the skin external preparation. Caused irritation can be reduced or prevented. The irritation-causing substance is not particularly limited as long as it is a component that can be generally blended into an external preparation for skin, but in the present invention, a fat-soluble drug component and a preservative can be mentioned. Excellent. Examples of the fat-soluble drug component include an ultraviolet absorber.

  Therefore, the present invention contains one or two selected from N-benzenesulfonylglutamic acid, N-benzoylglutamic acid, N-benzenesulfonylaspartic acid and N-benzoylaspartic acid, and a substance that causes irritation to the skin. It contains the skin external preparation characterized by these.

Examples of fat-soluble drugs and preservatives are shown below.
1. Retinol and its derivatives Retinol (all trans type, 13-cis type), retinol acetate, retinol palmitate and the like.

2. Ultraviolet absorber Paraaminobenzoic acid (abbreviated as PABA) PABA monoglycerin ester, N, N-dipropyl PABA ethyl ester, N, N-diethyl PABA ethyl ester, N, N-dimethyl PABA ethyl ester, N, N-dimethyl PABA butyl Ester, homomenthyl-N-acetylanthranilate, amyl salicylate, menthyl salicylate, homomenthyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate, p-isopropanol phenyl salicylate, 2-methoxyhexyl paramethoxycinnamate, di-p-methoxycinnamic acid-glyceryl mono-2-ethylhexanoate, octylcinnamate, ethyl-4-isopropylcinnamate, methyl-2,5-diisopropylcinnamate, Ethyl-2,4-diisopropylcinnamate, methyl-2,4-diisopropylcinnamate, propyl-p-methoxycinnamate, isopropyl-p-methoxycinnamate, isoamyl-p-methoxycinnamate, 2-ethoxyethyl-p -Methoxycinnamate, cyclohexyl-p-methoxycinnamate, ethyl-α-cyano-β-phenylcinnamate, 2-ethylhexyl-α-cyano-β-phenylcinnamate, glyceryl mono-2-ethylhexanoyl diparamethoxy Cinnamate, 3,4,5-trimethoxycinnamic acid-3-methyl-4- [methylbis (trimethylsiloxy) silyl] butyl, 2,4-dihydroxybenzophenone, 2,2′-dihydroxy-4-methoxybenzophenone, 2, 2'-dihydroxy-4. '-Dimethoxybenzophenone, 2,2', 4,4'-tetrahydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonate, 3- (4'-methyl) Benzylidene) -dl-camphor, 3-benzylidene-dl-camphor, 2-phenyl-5-methylbenzoxazole, 2,2′-dihydroxy-5-methylphenylbenztriazole, 2- (2′-hydroxy-5′-) t-octylphenyl) benztriazole, 2- (2′-hydroxy-5′-methylphenylbenztriazole), dibenzalazine, dianisoylmethane, 4-t-butyl-4′-methoxydibenzoylmethane, 5- (3,3 -Dimethyl-2-norbornylidene) -3-pentan-2-one and the like.

3. Preservatives Phenoxyethanol, benzoic acid and its salts, salicylic acid and its salts, phenol, sorbic acid and its salts, dehydroacetic acid and its salts, p-hydroxybenzoates, chlorocresol, hexachlorophene, resorcinol, isopropylmethylphenol, orthophenylphenol Benzalkonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, alkylisoquinolium bromide, trichlorocarbanilide, halocarban, Photosensitizer 201, trichlorohydroxydiphenyl ether, methylchloroisothiazolinone. Methyl isothiazolinone solution, bisabolol, alkyldiaminoethylglycine hydrochloride, trichlorosalicylanilide, tribromosalicylanilide, etc.

Especially in this invention, it uses suitably for the irritation | stimulation relaxation of the following ultraviolet absorber which has irritation.
2-Ethylhexyl paramethoxycinnamate (trade name: Pulsol MCX)
4-t-butyl-4′-methoxydibenzoylmethane (trade name: Pulsol 1789)
Methylbis (trimethylsiloxy) silylisopentyl trimethoxycinnamate (trade name: Sun Shelter SP)
Methyl paradimethylaminobenzoate (trade name: ESCALOL 506)

In the present invention, the compounding amount of the compound represented by the above general formula (I) is appropriately determined according to the compounding amount of the stimulus-causing substance such as a fat-soluble drug component (retinol and its derivative, ultraviolet absorber, preservative, etc.). Is done.
The compound represented by the above general formula (I) to be blended in the present invention is preferably blended in the range of 0.1 to 20.0% by mass with respect to the total amount of the external preparation for skin, more preferably 0. The range is from 5 to 10.0% by mass. If the amount is less than this, the desired effect cannot be obtained, and if the amount is more than this, the effect of the external preparation for skin is impaired.

The external preparation for skin of the present invention has an effect of mitigating and preventing irritation of sensitive skin and atopic patients, and also has an effect of mitigating the irritation caused by active agents and preparations.
In the external preparation for skin according to the present invention, any component that can be generally blended in cosmetics and pharmaceuticals can be blended. Specifically, UV absorbers, moisturizers, vitamins, whitening agents, astringents, refreshing agents, various medicinal ingredients such as extracts, surfactants, liquid fats, solid fats, waxes, ester oils, hydrocarbons Examples include, but are not limited to, oils, silicones, sterols, water-soluble polymers, oil-soluble polymers, chelating agents, neutralizing agents, pH adjusters, antioxidants, antibacterial agents, powders, fragrances, and pigments. Is not to be done.

  The preparation form of the external preparation for skin of the present invention is not limited, and for example, any property such as liquid, gel, paste, emulsion, cream, powder, solid, solution system, solubilization Any type of dosage form such as a system, an emulsifying system, a powder dispersion system, a water-oil two-layer system, a water-oil-powder three-layer system, a gel, and an aerosol is applied.

In addition, the form of use is also arbitrary, and for example, it can be used for makeup cosmetics, aromatic cosmetics, bathing agents, etc. in addition to facial cosmetics and foundations such as lotion, milky lotion, cream, cosmetic liquid, pack, etc. It is not limited.
The external preparation for skin of the present invention is one in which the irritation caused by the stimulant or preparation in the external preparation for skin and the irritation generated at the time of application are reduced, alleviated or prevented.

  The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto. Unless otherwise specified, the amount is shown in mass%.

Examples 1 to 4, Comparative Examples 1 and 2
Samples having the compositions shown in Table 1 below were prepared by a conventional method and subjected to a stimulus relaxation test.

(Irritation relaxation test)
The stimulus relaxation property was evaluated by the test methods shown below for Examples 1 to 4 and Comparative Examples 1 and 2 described in Table 1. The results are shown in Table 2 below.

(Test method)
A patch test was performed by applying 0.05 ml of each sample containing a stimulus-causing substance and a stimulus-relaxing agent to the inner side of the upper arm of subjects (25 women and 25 men).

(Evaluation methods)
The condition of the skin of the coated area (skin reaction such as erythema, edema, crust) was visually determined, and the presence or absence of irritation was determined based on the following criteria based on the subject's self-report.

(Evaluation criteria)
A: No erythema or irritation.
○: Almost no erythema was observed, but slight irritation or slight skin roughness was observed.
Δ: Slight erythema was observed and there was a clear irritation.
X: Obvious erythema or edema, crust was observed, and there was a clear irritation.

As is clear from the results of Table 2, in Examples 1 to 4 in which benzoyl and / or benzenesulfonylaminodicarboxylic acid was blended as a stimulus relaxation agent, Comparative Example 1 in which no stimulus relaxation agent was blended and other stimulus relaxation agents were blended It turns out that it is excellent in the stimulus relaxation effect compared with any of the comparative examples 2 which were done.
The formulation example of the skin external preparation which mix | blended the irritation reducing agent of this invention is given to the following.

Example 5 (Sunscreen)
2-Ethylhexyl paramethoxycinnamate 7.5
4-t-butyl-4'-methoxydibenzoylmethane 0.1
Titanium dioxide 5.0
Decamethylcyclopentasiloxane 30.0
POE / methylpolysiloxane copolymer 3.0
Organically modified montmorillonite 0.8
1,3-butylene glycol 5.0
Arbutin 5.0
N-benzoyl-L-glutamic acid 3.0
Sodium hydroxide 0.48
Preservative appropriate amount Fragrance appropriate amount Purified water Residue

Example 6 (cream)
(A)
Squalane 6.0
Vaseline 5.0
Stearyl alcohol 3.0
Stearic acid 3.0
Glyceryl monostearate 3.0
Polyethyl acrylate 1.0
4-t-butyl-4′-methoxydibenzoylmethane 7.5
Polyamide resin powder 5.0
Ethanol 40.0
Preservative appropriate amount perfume appropriate amount (B)
1,3-butylene glycol 7.0
Edetate trisodium 0.05
Cationic thickener 3.0
Lactic acid 0.6
N-Benzenesulfonyl-L-glutamic acid 3.0
Sodium hydroxide 0.86
Purified water residue (production method)
The component (A) is heated and melted, and (B) is added with stirring. The mixture is processed with a homomixer to make the emulsified particles fine, and then rapidly cooled with stirring to obtain a cream.

Example 7 (skin lotion)
(A)
2-Ethylhexyl paramethoxycinnamate 2.0
Pentaerythrityl tetraoctanoate 1.0
Polyoxyethylene (20) oleyl alcohol ether 0.5
Ethanol 60.0
Perfume appropriate amount Preservative appropriate amount (B)
Sorbit 4.0
Dipropylene glycol 6.0
Lactic acid 0.1
Citric acid 0.1
Sodium citrate 0.05
N-benzoyl-L-glutamic acid 3.0
Sodium hydroxide 0.51
Sodium hydroxymethoxybenzophenone sulfonate appropriate amount Trisodium edetate appropriate amount Purified water Residue (Production method)
Adjust (B). Separately, other components of (A) are dissolved in ethanol to prepare (A), and this is added to (B) solubilized and filtered to obtain a lotion.

Example 8 (milky lotion)
(A)
Stearic acid 2.0
Cetyl alcohol 0.5
Liquid paraffin 10.0
Polyoxyethylene (10) oleate 1.0
Sorbitan triolate 1.0
2-Ethylhexyl paramethoxycinnamate 3.0
Pentaerythrityl tetraoctanoate 1.5
Isopropyl myristate 2.0
Silica 3.0
Preservative appropriate amount perfume appropriate amount (B)
Diprene glycol 5.0
Triethanolamine 1.0
Hectorite 1.0
Citric acid 0.2
Ethanol 55.0
N-Benzenesulfonyl-L-aspartic acid 3.0
Sodium hydroxide 0.88
Purified water residue (production method)
Adjust (B) and keep at 70 ° C. The component (A) is mixed, heated and melted and kept at 70 ° C. (A) is added to (B), and the mixture is uniformly emulsified with a homomixer and rapidly cooled with stirring to obtain an emulsion.

Example 9 (sunscreen hair gel)
(A)
Carbopol 940 0.6
(B)
N-benzoyl-L-glutamic acid 3.0
Sodium hydroxide 0.48
Purified water residue (C)
Triethanolamine 0.1
(D)
Ethanol 14.0
2-Ethylhexyl paramethoxycinnamate 7.5
Methoxyethyl acrylate / hydroxyethyl acrylate / butyl acrylate copolymer 1.0
Polyethylene glycol 1.0
Dimethicone copolymer 4.0
Methylparaben 0.25
Propylparaben 0.05
Perfume appropriate amount (production method)
(A) is dissolved in (B) with stirring, and after (C) is added, it is dispersed with a disperser. D is added to this and stirred to obtain the desired hair gel.

Example 10 (sunscreen emulsifying foundation)
(A)
Purified water residue N-benzenesulfonyl-L-glutamic acid 1.5
1,3-butylene glycol 5.0
Ethanol 7.0
(B)
Talc 7.0
Titanium dioxide 10.0
Zinc oxide 2.0
Silica anhydride 2.0
Nylon powder 4.0
Color pigment 2.0
(C)
2-Ethylhexyl paramethoxycinnamate 15.0
Octamethylcyclotetrasiloxane 10.0
Rosin pentaerythlit ester 1.5
Neopentyl glycol diisooctanoate 5.0
Glycerin triisooctanoate 2.0
Polyoxyethylene-modified dimethylpolysiloxane 1.5
Trimethylsiloxysilicate resin 5.0
(Manufacturing method)
After (A) is stirred, (B) sufficiently mixed and ground is added and homomixed. (C) is dissolved and then added to this and homomixed to obtain a sunscreen emulsified foundation.

Claims (10)

A skin external preparation characterized by containing a benzoylaminodicarboxylic acid, benzenesulfonylaminodicarboxylic acid represented by the following general formula (I), or a pharmaceutically acceptable salt adduct thereof.

(In the formula, X ¹ , X ² and X ³ are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, an amino group, and 1 to 1 carbon atoms. 4 represents an alkylamino group, an acyl group having 1 to 4 carbon atoms, a nitro group, a cyano group, a halogen atom or a trifluoromethyl group, Y represents a carbonyl group or a sulfonyl group, and n represents 1 or 2. ) In the general formula (I), X ¹ , X ² and X ³ are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, or a hydroxyl group. The external preparation for skin according to claim 1.   The external preparation for skin according to claim 1, wherein Y in the general formula (I) is a sulfonyl group.   The skin external preparation according to claim 1, wherein the compound represented by the general formula (I) is N-benzenesulfonylglutamic acid, N-benzoylglutamic acid, N-benzenesulfonylaspartic acid or N-benzoylaspartic acid. .   The skin external preparation according to claim 1, comprising a compound represented by the general formula (I) and a substance that causes irritation to the skin.   6. The external preparation for skin according to claim 5, wherein the substance that causes irritation to the skin is one or more selected from fat-soluble drug components and preservatives.   The skin external preparation according to claim 6, wherein the fat-soluble drug component is an ultraviolet absorber. A skin irritation relieving agent comprising a compound represented by the following general formula (I) or a pharmaceutically acceptable salt adduct thereof.

(In the formula, X ¹ , X ² and X ³ are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, an amino group, and 1 to 1 carbon atoms. 4 represents an alkylamino group, an acyl group having 1 to 4 carbon atoms, a nitro group, a cyano group, a halogen atom or a trifluoromethyl group, Y represents a carbonyl group or a sulfonyl group, and n represents 1 or 2. )   9. The skin irritation alleviation according to claim 8, wherein the compound represented by the general formula (I) is N-benzenesulfonylglutamic acid, N-benzoylglutamic acid, N-benzenesulfonylaspartic acid or N-benzoylaspartic acid. Agent. A method for alleviating skin irritation, comprising relieving skin irritation using a compound represented by the following general formula (I) or a pharmaceutically acceptable salt adduct thereof.

(In the formula, X ¹ , X ² and X ³ are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, an amino group, and 1 to 1 carbon atoms. 4 represents an alkylamino group, an acyl group having 1 to 4 carbon atoms, a nitro group, a cyano group, a halogen atom or a trifluoromethyl group, Y represents a carbonyl group or a sulfonyl group, and n represents 1 or 2. )