JPH09263511A - Preparation for external use for skin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject preparation capable of persisting an excellent flexibility-imparting effect to horny layers and an excellent skin wrinkle- improving effect for a long time and useful for skin-softening cosmetics, antiaging cosmetics, etc. SOLUTION: This preparation for external uses for skins contains a guanidine derivative of formula I (R<1> is a hydrocarbon group, an aromatic ring group, an aralkyl group, etc.; R<2> is H, a hydrocarbon group) or its acid adduct, a synthetic sphingosine derivative of formula II (R<4> is a 4-40C hydrocarbon group; R<5> , R<6> , R<7> , R<8> , R<9> are each H, a 1-10C hydrocarbon; X, Y are each H, a 1-6C alkyl which may have an oxygen atom), and an organic acid such as a dicarboxylic acid or its ester. The guanidine derivative, the synthetic sphingosine derivative, and the organic acid or its ester are preferably compounded in amounts of 0.001-50wt.%, 0.0001-10wt.% and 0.001-30wt.%, respectively, in the preparation.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an external preparation for skin which is excellent in imparting flexibility to the stratum corneum and suppressing and eliminating wrinkles.

[0002]

The stratum corneum, which is the outermost layer of the skin, becomes dry or rough due to weather conditions such as low temperature and low humidity in winter and the like, as well as excessive use of detergents and solvents. Such changes in the skin are due to the loss of the hygroscopic water-soluble component called NMF (Natural Moisturizing Factor) in the stratum corneum, which reduces the water content in the stratum corneum and reduces flexibility. Is believed to be. Therefore,
Conventional cosmetics for softening the skin include various moisturizers such as organic acids and amino acids which are natural moisturizing ingredients for the purpose of supplying a large amount of water to the stratum corneum and keeping it for a long time. It is compounded.

As such a skin softening cosmetic, for example, an organic acid in which α-oxy acid having a softening effect on the stratum corneum is blended with the cosmetic has been proposed (for example, JP-A-55). -19291). However, α-oxy acid has a transient effect, and has a low pH range (pH 2 to 4) that inhibits normal skin physiology.
There is a problem in that it only exerts its effect.

In order to solve this problem, there is also a cosmetic composition in which a strong alkali such as sodium hydroxide or potassium hydroxide or an amine such as triethanolamine is added to adjust to a neutral pH range. However, these strong alkalis
When blended in a large amount, stability is impaired and it is difficult to adjust to the pH range of the skin, so there is a problem that it is difficult to keep the quality of the cosmetic constant.
On the other hand, amines may cause an allergic reaction, which is not preferable in terms of safety.

In order to solve the problem in the case of blending α-oxy acid in this way, a combination of α-oxy acid and a basic amino acid has been proposed (for example, Japanese Patent Publication No. 30566/1990). Gazette), its skin softening effect is not fully satisfactory. In addition, cosmetics containing amino acids and their derivatives for the purpose of softening due to improvement of moisturizing effect, those containing protein degradation products such as yoquinin (for example, JP-B-58-8007) and various peptides are added. (For example, JP-A-48-2
3944, 62-99315 and JP-A-2-178207) have been proposed. But,
The skin softening effect of these amino acids and peptides,
After all it was not completely satisfactory.

On the other hand, maintaining healthy and beautiful skin is a problem of great concern, especially for women.
However, the condition of the skin is always affected by factors such as humidity, ultraviolet rays, cosmetics, aging, diseases, stress, and eating habits, and as a result, various skin problems such as deterioration of various functions of the skin and aging of the skin are caused. Occur. Of these, wrinkles are caused by aging of the skin due to aging and photoaging due to exposure to sunlight. That is, the cells that make up the dermis fibers become smaller and less with exposure to sunlight and age, and especially the collagen fibers are largely lost, the dermis degenerates, the subcutaneous adipose tissue decreases, and the skin ages. It causes wrinkles, relaxation and loss of elasticity.

Conventionally, various compositions and methods have been proposed in order to suppress or treat the aging effect such as wrinkles (Japanese Patent Laid-Open Nos. 62-185005 and 62-502546). JP-A-2-72157, JP-A-2-288822, JP-A-7-41419, and JP-A-6-510542). However, none of these was sufficiently satisfactory in the effect of improving wrinkles. Therefore, a skin external preparation having an excellent effect of improving wrinkles has been desired.

[0008]

Therefore, the present invention solves the above problems and can impart flexibility to the stratum corneum without impairing normal skin physiology and suppress wrinkles,
It is an object of the present invention to provide an external preparation for skin which is excellent in the effect of disappearing and has a good feeling in use.

[0009]

Under such circumstances, the inventors of the present invention have conducted extensive studies to achieve the above object, and as a result, when a guanidine derivative having a specific structure or an acid addition salt thereof was used for skin, a basic amino acid was obtained. The present invention has found that an excellent effect of imparting flexibility to the stratum corneum can be obtained as compared with the case of combining the amino acids alone or the basic amino acids and the α-oxyacids, and further excellent wrinkle improving effect can be obtained, and the present invention Has been completed.

That is, the present invention provides the following general formula (1);

[0011]

Embedded image

(In the formula, R ¹ represents a linear or branched hydrocarbon group, or an aromatic ring group, an aralkyl group, a cycloalkyl group or an oxacycloalkyl group which may have a substituent, and R 1 ² represents a hydrogen atom or a linear or branched hydrocarbon group), or a guanidine derivative represented by the formula or an acid addition salt thereof, to provide an external skin preparation.

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION The guanidine derivative or its acid addition salt used in the present invention is represented by the above general formula (1). In the formula, examples of the linear or branched hydrocarbon group represented by R ¹ include saturated or unsaturated linear or branched alkyl or alkenyl groups having 1 to 12 carbon atoms,
Preferably, an alkyl group having 1 to 8 carbon atoms is mentioned, and examples thereof include methyl, ethyl, n-propyl, isopropyl and n-.
Butyl, 2-methylpropyl, t-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, 2-
An ethylhexyl group may be mentioned. Of these, methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, n-pentyl and n-hexyl groups are particularly preferable.

The aromatic ring group has, for example, 6 to 14 carbon atoms.
And aromatic ring groups having 6 to 10 carbon atoms are particularly preferable. Specific examples of the aromatic ring group, phenyl, pentalenyl, indenyl, naphthyl, azulenyl, heptanenyl, biphenylenyl, indacenyl, acenaphthenyl, fluorenyl, pentalenyl, phenanthryl,
Examples thereof include anthryl group, and phenyl group is particularly preferable.

Examples of the aralkyl group include an aralkyl group having 7 to 12 carbon atoms, such as a benzyl group, a phenethyl group, a naphthylmethyl group and the like, and a benzyl group is particularly preferable.

The cycloalkyl group has 3 to 8 carbon atoms.
And cycloalkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,
Cycloheptyl, cyclooctyl, bicyclo [2.2.
1] heptyl, bicyclo [2.2.2] octyl group and the like, especially cyclopentyl, cyclohexyl,
A cycloheptyl group is preferred.

Examples of the oxacycloalkyl group include oxacycloalkyl groups having 2 to 7 carbon atoms, such as oxacyclopropyl, oxacyclobutyl, oxacyclopentyl, oxacyclohexyl and oxacycloheptyl groups, and particularly oxacyclopentyl group. An oxacyclohexyl group is preferred.

Further, these aromatic ring groups represented by R ¹
The aralkyl group, the cycloalkyl group or the oxacycloalkyl group may have a substituent, and examples of the substituent include a hydroxyl group, alkyl, hydroxyalkyl, -OR ³ ,
Examples thereof include -COOH, -COOR ³ , -OCOR ³ , oxoalkyl, carboxyalkyl group and the like (R ³ represents a linear or branched hydrocarbon group).

Here, examples of the alkyl group as a substituent include linear or branched alkyl groups having 1 to 8 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl and 1-. Methylpropyl, 2-methylpropyl, t-butyl, n-pentyl, 2,2-dimethylpropyl, n-hexyl, n-heptyl, n-octyl, 2-ethylhexyl group and the like, particularly methyl,
Ethyl and isopropyl groups are preferred.

The hydroxyalkyl group has 1 carbon atom.
To 8 hydroxyalkyl groups, especially 1 carbon atoms.
~ 6 hydroxyalkyl groups are more preferred. Specific examples of the hydroxyalkyl group include a hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl group and the like, and a hydroxymethyl, 2-hydroxyethyl and 3-hydroxypropyl group are particularly preferred.

The oxoalkyl group has 2 to 8 carbon atoms.
And an oxoalkyl group having 2 to 4 carbon atoms is particularly preferable. Specific examples of the oxoalkyl group include 1-oxoethyl (acetyl), 1-oxopropyl, 2-oxopropyl, 1-oxobutyl,
-Oxobutyl, 3-oxobutyl, 1-oxopentyl, 2-oxopentyl, 3-oxopentyl, 4-oxopentyl, 1-oxohexyl, 2-oxohexyl, 1-oxoheptyl, 1-oxooctyl and the like. And a 1-oxoethyl (acetyl) group is particularly preferred.

The carboxyalkyl group has 2 carbon atoms.
~ 7 carboxyalkyl groups, especially 2 carbon atoms
-5 carboxyalkyl groups are preferred. Specific examples of the carboxyalkyl group include a carboxymethyl, carboxyethyl, carboxypropyl, carboxybutyl group and the like, and a carboxyethyl and carboxybutyl group are particularly preferable.

Further, the hydrocarbon group represented by R ³ includes a linear or branched alkyl group having 1 to 6 carbon atoms, and an alkyl group having 1 to 5 carbon atoms is particularly preferable. Specific examples of the alkyl group include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, te
An rt-butyl group and the like can be mentioned, and a methyl, ethyl, n-propyl and isopropyl group are particularly preferable.

R ¹ is especially methyl, ethyl or n-
Propyl, isopropyl, n-butyl, n-pentyl,
n-hexyl, phenyl, benzyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-hydroxyphenyl, 2-methoxyphenyl, 2-ethoxyphenyl, 3-hydroxyphenyl, 3-methoxyphenyl, 3- Ethoxyphenyl, 4-hydroxyphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 2
-Carboxyphenyl, 2- (methoxycarboxy) phenyl, 3-carboxyphenyl, 3- (methoxycarboxy) phenyl, 4-carboxyphenyl, 4- (methoxycarboxy) phenyl, 4-acetylphenyl,
Preferred are 4-acetoxyphenyl, cyclopentyl, cyclohexyl, 4-carboxycyclohexyl, glucopyranosyl and the like.

Examples of the hydrocarbon group represented by R ² include those similar to those represented by R ¹ .
As the group represented by R ² , a hydrogen atom and a methyl group are particularly preferable.

Although some guanidine derivatives (1) have an asymmetric carbon atom, any of these stereoisomers and mixtures thereof can be used in the present invention.

Specific examples of the guanidine derivative (1) include methylguanidine, ethylguanidine, n-propylguanidine, isopropylguanidine, n-butylguanidine, 2-methylpropylguanidine, t-butylguanidine, n-pentylguanidine, n. -Hexylguanidine, n-heptylguanidine, n-octylguanidine, N, N-dimethylguanidine, N, N-diethylguanidine, phenylguanidine, N-methyl-N-
Phenylguanidine, 2-methylphenylguanidine,
3-methylphenylguanidine, 4-methylphenylguanidine, 2-hydroxyphenylguanidine, 3-hydroxyphenylguanidine, 4-hydroxyphenylguanidine, 2-methoxyphenylguanidine, 3-methoxyphenylguanidine, 4-methoxyphenylguanidine, 2- Ethoxyphenylguanidine, 3-ethoxyphenylguanidine, 4-ethoxyphenylguanidine, 2-guanidinobenzoic acid, 3-guanidinobenzoic acid, 4-guanidinobenzoic acid, 2- (1-methylguanidino) benzoic acid, 3- (1- Methylguanidino) benzoic acid, 4- (1-methylguanidino) benzoic acid, 2- (4
-Guanidinophenyl) acetic acid, 3- (4-guanidinophenyl) propanoic acid, 4- (4-guanidinophenyl)
Butanoic acid, 2,4,6-trimethylphenylguanidine, 2-methoxy-5-methylphenylguanidine, cyclohexylguanidine, cyclopentylguanidine,
Benzylguanidine, glucopyranosylguanidine, deoxyguanidinoinositol, 4-oxacyclohexylguanidine, 2-guanidinocyclohexanecarboxylic acid, 3-guanidinobenzoic acid 1-methylethyl ester, 4-acetylphenylguanidine, 4-guanidinophenyl acetate, etc. However, the present invention is not limited to these.

Of these guanidine derivatives (1),
Particularly, methylguanidine, ethylguanidine, n-propylguanidine, isopropylguanidine, n-butylguanidine, 2-methylpropylguanidine, t-butylguanidine, n-pentylguanidine, n-hexylguanidine, phenylguanidine, N-methyl-N. -Phenylguanidine, 4-hydroxyphenylguanidine, 4-methoxyphenylguanidine, 4-ethoxyphenylguanidine, 3- (4-guanidinophenyl) propanoic acid, 4- (4-guanidinophenyl) butanoic acid,
2-Methoxy-5-methylphenylguanidine, cyclohexylguanidine, benzylguanidine, glucopyranosylguanidine and 4-guanidinophenyl acetate are preferred.

The acid for forming the acid addition salt of the guanidine derivative may be either an organic acid or an inorganic acid such as formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, hexanoic acid, heptanoic acid, octane. Acid, nonanoic acid,
Decanoic acid, lauric acid, myristic acid, palmitic acid,
Monocarboxylic acids such as stearic acid, acrylic acid, methacrylic acid, crotonic acid, isocrotonic acid, phenylacetic acid, cinnamic acid, benzoic acid, sorbic acid, nicotinic acid, urocanic acid, and pyrrolidonecarboxylic acid; oxalic acid, malonic acid, amber Acid, glutaric acid, adipic acid, pimelic acid,
Dicarboxylic acids such as cork acid, azelaic acid, sebacic acid, maleic acid, fumaric acid, phthalic acid, terephthalic acid; glycolic acid, lactic acid, malic acid, tartaric acid, citric acid, o,
Hydroxy acids such as m or p-hydroxybenzoic acid; glycine, alanine, β-alanine, valine, leucine, phenylalanine, tyrosine, serine, threonine, methionine, cysteine, cystine, proline, hydroxyproline, pipecolic acid, tryptophan, aspartic acid. , Amino acids such as asparagine, glutamic acid, glutamine, lysine, histidine, ornithine, arginine and aminobenzoic acid; lower alkyl sulfonic acids such as methane sulfonic acid and trifluoromethane sulfonic acid; aryl sulfones such as benzene sulfonic acid and p-toluene sulfonic acid Acids; hydrohalic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid and hydroiodic acid; inorganic acids such as perchloric acid, sulfuric acid, nitric acid, phosphoric acid, carbonic acid and bicarbonate.

Of these, the guanidine derivative represented by the formula (1) or its acid addition salt can be obtained, for example, by the production method represented by the following reaction formula.

[0031]

Embedded image

(In the formula, R ¹ and R ² are the same as above)

That is, the guanidine derivative (1) or an acid addition salt thereof can be obtained by reacting the amine derivative (3) with a guanidylating reagent.

As the guanidylating reagent, known guanidylating reagents such as cyanamide, S-alkylisothiourea, O-alkylisourea, aminoiminomethanesulfonic acid, 3,5-dimethyl-1-guanylpyrazole,
1H-pyrazole-1-carbamidine and the like can be mentioned.

In the reaction, when S-alkylisothiourea, O-alkylisourea, 3,5-dimethyl-1-guanylpyrazole, 1H-pyrazole-1-carbamidine is used, barium hydroxide, calcium hydroxide, and hydroxide are used. Magnesium, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium hydrogen carbonate, sodium carbonate, aqueous ammonia; tertiary amines such as triethylamine, N, N-dimethylaniline, N, N-dimethylpiperazine and N-methylpiperazine; In the presence of a base such as pyridine,
It may be stirred at 25 ° C to 200 ° C for 1 hour to 72 hours.
When cyanamide is used, 0 ° C to 200 ° C,
Stir for 1 hour to 72 hours, or in the presence of the acid exemplified as the acid addition product of guanidine, 25 ° C to 150 ° C.
It suffices to stir at 1 ° C for 1 to 72 hours.

After completion of the reaction, if necessary, an acid can be added by a conventional method to isolate as an acid addition salt.

These guanidine derivatives or acid addition salts thereof can be used alone or in combination of two or more,
The compounding amount in the external preparation for skin is preferably 0.001 to 50% by weight, particularly 0.001 to 30% by weight, and further 0.1.
The blending amount of 01 to 20% by weight is preferable because the softening effect and wrinkle improving effect of the stratum corneum of the skin are further enhanced.

Further, in the external preparation for skin of the present invention, the following general formula (2);

[0039]

Embedded image

(In the formula, R ⁴ represents a linear, branched or cyclic saturated or unsaturated hydrocarbon group having 4 to 40 carbon atoms.
⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ each represent a hydrogen atom or a hydrocarbon group having 1 to 10 carbon atoms which may be substituted with one or more hydroxyl groups, and X and Y are hydrogen atoms or A synthetic sphingosine derivative represented by (indicating an alkyl group having 1 to 6 carbon atoms which may have an oxygen atom) can be blended.

In the general formula (3), the number of carbon atoms represented by R ⁴ is 4
As the linear, branched or cyclic saturated or unsaturated hydrocarbon group of -40, for example, n-butyl group, sec-butyl group, pentyl group, hexyl group, octyl group, 2-ethylhexyl group, decyl group, Dodecyl group, tetradecyl group,
Pentadecyl group, hexadecyl group, octadecyl group,
5,7,7-trimethyl-2- (1,3,3-trimethylbutyl) -octyl group, 2-heptylundecyl group,
Alkyl group such as methyl-branched isostearyl group; butenyl group, hexenyl group, oleyl group, 9-octadecyl group, 9,12-octadecadienyl group, 3,7-dimethylocta-2,6-dienyl group, 3, Examples thereof include alkenyl groups such as 7,11-trimethyl-2,6,10-dodecatrienyl group, cycloalkyl groups such as cyclopentyl group and cyclohexyl group; aryl groups such as phenyl group, tolyl group and naphthyl group. 4 carbon atoms in the present invention
A straight-chain or branched-chain saturated hydrocarbon group of -40 is more preferable, and among these, a tetradecyl group, an octadecyl group, and a methyl-branched isostearyl group are particularly preferable.

The hydrocarbon group having 1 to 10 carbon atoms which may be substituted by one or more hydroxyl groups of R ^{5 to} R ⁹ is:
Examples thereof include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, a hydroxymethyl group, a hydroxyethyl group, a 2-hydroxyethyl group, and a 3,3,3-trihydroxypropyl group. As R ^{5 to} R ⁹ , Is preferably a hydrogen atom or a methyl group.

Examples of the alkyl group having 1 to 6 carbon atoms which may have oxygen atoms of X and Y include glucosyl group, fructosyl group, galactosyl group, mannosyl group, methyl group, ethyl group, propyl group and hexyl group. , 2-hydroxyethyl group, 3-hydroxyethyl group, 4-hydroxypropyl group, 5-hydroxy-6-hydroxybutyl group, 2,3-dihydroxypropyl group, 2- (1,2,2
3-trihydroxypropyl) methyl group, 3- (2,3
-Dihydroxypropyloxy) -2-hydroxyethyl group may be mentioned, and as X and Y, a hydrogen atom, 2-
The hydroxyethyl group is particularly preferred.

These synthetic sphingosine derivatives can be used alone or in combination of two or more, and the compounding amount in the external preparation for skin is preferably 0.0001 to 10% by weight, particularly 0.001 to 2% by weight. It is preferable to mix it, because not only the effect of softening the stratum corneum of the skin and the effect of improving wrinkles but also the feeling of use are improved.

The external preparation for skin of the present invention may further contain an organic acid or an inorganic acid such as phosphoric acid, sulfuric acid or hydrochloric acid,
It is preferable to blend these, because the wrinkle improving effect can be further enhanced.

The organic acid is a guanidine derivative (A).
Is not particularly limited as long as it is not included in the above, and examples thereof include α- or β-hydroxycarboxylic acid, dicarboxylic acid, fatty acid and esters thereof, and these are 1
More than one species can be blended. Examples of these organic acids include the following formula (4) or (5);

[0047]

[Chemical 6]

[In the formula (4), R ¹⁰ and R ¹¹ each represent a hydrogen atom or a saturated or unsaturated linear, branched or cyclic alkyl group, aralkyl group or aryl group having 1 to 28 carbon atoms, and q Represents an integer of 1 to 9 and r represents an integer of 0 to 23. In the formula (5), s represents an integer of 0 to 9 and t is 0.
To an integer of 23] and esters thereof.

The fatty acids include linoleic acid and γ-
Linoleic acid, corumbic acid, nicosa- (η-6,9,
13) -trienoic acid, arachidonic acid, α-linolenic acid, thymmonodic acid, hexaenoic acid, isostearic acid,
Undecylenic acid, stearic acid, palmitic acid, behenic acid, myristic acid, coconut oil fatty acid, lauric acid, lanolinic acid, DHA, hydroxy fatty acids such as 12-hydroxystearic acid, monoalkyl phosphoric acids such as cetyl phosphoric acid, dialkyl phosphorus Acids and the like can be mentioned.

Specific examples of these organic acids include ascorbic acid, epsilon aminocaproic acid, erythorbic acid, citric acid, succinic acid, tartaric acid, sorbic acid, dehydroacetic acid, lactic acid, urocanic acid, edetic acid, oxybenzonesulfonic acid, orotic acid. , Capric acid, glycolic acid, cerotic acid, nicotinic acid, hydroxyethanediphosphonic acid, phytic acid, fumaric acid, malic acid, levulinic acid, acrylic acid and oligomers or polymers thereof.

In the present invention, among these organic acids and inorganic acids, the dicarboxylic acid represented by the formula (6) is preferable, and particularly succinic acid can further enhance the effect of softening the stratum corneum of the skin and the effect of improving wrinkles. Preferred for. The organic acid or the inorganic acid can be used alone or in combination of two or more, and the compounding amount in the external preparation for skin is 0.01 to.
It is preferably 30% by weight, and particularly preferably blended in an amount of 0.1 to 20% by weight because the effect of improving wrinkles as well as the effect of improving wrinkles can be further enhanced. The compounding ratio of these organic acid and inorganic acid to the guanidine derivative or its acid addition salt is 0.5: 99.5 to 99.5: 0.5 by weight.
Is preferable, and 5:95 to 95: 5 is particularly preferable because the effect of softening the stratum corneum of the skin and the effect of improving wrinkles can be further enhanced.

The external preparation for skin of the present invention may further contain an oil component. The oil content is not particularly limited, and examples thereof include hydrocarbons such as solid or liquid paraffin, crystal oil, ceresin, ozokerite, montan wax, squalane, squalene, olive oil, carnauba wax, lanolin, jojoba oil, glycerin monostearate ester. Ester oils such as glycerin distearate, glycerin monooleate, isopropyl stearate, neopentyl glycol dicaprate, cholesterol isostearate, higher fatty acids such as stearic acid and palmitic acid, higher alcohols such as cetanol and stearyl alcohol , Naturally extracted sphingosine derivatives and the like, and these can be used alone or in combination of two or more.

When these oils are blended, the external preparation for skin of the present invention is preferably blended in an amount of 0.001 to 50% by weight, more preferably 0.005 to 30% by weight.

The external preparation for skin of the present invention may further contain sterols. Examples of the sterols include cholesterol, provitamin D ₃ , campesterol, stegmasteranol, stegmasterol, 5-dihydrocholesterol, α-spinasterol, paristerol, clionasterol, γ-sitosterol, stegmasterol, salgasterol, Apenasterol, ergostanol, sitosterol,
Corbiterol, chondrilasterol, polyferrasterol, haliclonasterol, neosvongosterol, fucosterol, aptostanol, ergostadienol, ergosterol, 22-dihydroergomaterol, brassicasterol, 24-methylenecholesterol, 5-dihydro. Ergosterol, dehydroergosterol, fungisterol, cholestanol, coprostanol, dimosterol, 7-hetcholesterol, latosterol, 22-dehydrocholesterol, β-sitosterol, cholestatriene-3β.
-Ol, coprostanol, cholestanol, ergosterol, 7-dehydrocholesterol, 24-dehydrocholestraven-3 beta-ol, equilenin, equilin, estrone, 17 beta-estradiol, androst-4-en-3 beta, 17 beta-diol. , Dehydro shrimp androsterone, and the like, and one or more of them can be used.

When these sterols are blended, the external preparation for skin of the present invention is preferably blended in an amount of 0.001 to 50% by weight, particularly preferably 0.005 to 30% by weight.

A surfactant may be further added to the external preparation for skin of the present invention. Examples of the surfactant include polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbitol fatty acid ester, glycerin fatty acid ester, polyoxyethylene hydrogenated castor oil alkyl sulfate, polyoxyethylene. Examples thereof include ethylene alkyl sulfate ester, alkyl phosphate ester, polyoxyethylene alkyl phosphate ester, fatty acid alkali metal salt, sorbitan fatty acid ester, glycerin fatty acid ester, and alkyl glyceryl ether. These may be used alone or in combination. it can.

When these surfactants are blended,
The external preparation for skin of the present invention preferably contains 0.001 to 50% by weight, and more preferably 0.005 to 30% by weight.

The external preparation for skin of the present invention may further contain a water-soluble polyhydric alcohol. As the water-soluble polyhydric alcohol, one having two or more hydroxyl groups in the molecule, for example, ethylene glycol, propylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, dipropylene glycol, glycerin and diglycol Examples thereof include polyglycerin such as glycerin, triglycerin, and tetraglycerin, glucose, maltose, maltitol, sucrose, fructose, xylitol, sorbitol, maltotriose, threitol, erythritol, and starch-degrading sugar reducing alcohols. These are 1 More than one species can be used.

When these water-soluble polyhydric alcohols are blended, the blending amount in the external preparation for skin can be appropriately set according to the dosage form, but it is usually preferable to blend 0.001 to 75% by weight. It is particularly preferable to add 0.1 to 25% by weight.

A powder may be further added to the external preparation for skin of the present invention. Examples of this powder include mica,
Extenders such as talc, sericite, kaolin, nylon powder, polymethylsilsesquioxane, inorganic pigments such as pearl, Red No. 202, Red No. 226, Yellow No. 4,
Examples thereof include organic pigments such as aluminum lake, inorganic powders for protecting ultraviolet rays such as zinc oxide, titanium oxide, zirconium oxide and iron oxide. These powders are treated with silicone such as methylhydrogenmethylpolysiloxane, trimethylsiloxysilicic acid and methylpolysiloxane, fluorine treatment with perfluoroalkyl phosphate ester, perfluoroalcohol and the like, amino acid treatment with N-acylglutamic acid and the like, Those treated with lecithin, metal soap, fatty acid, alkyl phosphate, etc. can also be used.

When these powders are blended, the blending amount in the external preparation for skin can be appropriately set according to the dosage form, but it is usually preferable to blend 0.001 to 50% by weight, particularly 0 It is preferable to add 0.005 to 30% by weight.

The external preparation for skin of the present invention may further contain silicones. The silicones are not particularly limited as long as they are usually blended in cosmetics, for example, octamethylpolysiloxane,
In addition to tetradecamethylpolysiloxane, methylpolysiloxane, highly polymerized methylpolysiloxane, methylphenylpolysiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane and other methylpolycyclosiloxanes, trimethylsiloxysilicic acid, and poly Examples thereof include modified silicones such as ether / alkyl modified silicones and alkylglyceryl ether modified silicones.

When these silicones are blended, the blending amount in the external preparation for skin of the present invention can be appropriately set according to the dosage form, but usually 0.001 to 50% by weight is preferable. , Especially 0.005 to 30% by weight
It is preferable to mix them.

Further, the external preparation for skin of the present invention may contain various components which are usually contained in cosmetics, quasi-drugs, pharmaceuticals, etc. within a range not impairing the object of the present invention. Examples of such components include inorganic salts such as magnesium sulfate, potassium sulfate, sodium sulfate, magnesium chloride, sodium chloride; polyvinyl alcohol, carboxyvinyl polymer, carboxymethyl cellulose, gelatin, tragacanth gum, xanthan gum,
Examples thereof include viscosity adjusting agents such as hyaluronic acid, tuberose extract, agarose and sodium alginate; antiseptics such as parabens, pH adjusting agents, wetting agents, ultraviolet absorbers, dyes, medicinal ingredients, and fragrances.

The pH of the external preparation for skin of the present invention is preferably 2 to 11, and particularly preferably 3 to 8 because the normal physiological function of the skin can be maintained. The external preparation for skin of the present invention can be produced according to a usual method, and is an emulsion type,
It can be made into a desired dosage form such as dispersion type, two-layer type, solubilization type, gel, etc., and can be made into lotion, emulsion, cream, pack, foundation, etc. It can also be in the form of a pharmaceutical external preparation such as an agent, an ointment or a cream.

[0066]

The external preparation for skin of the present invention can exert an excellent effect of imparting flexibility to the stratum corneum for a long time, and can impart a good feeling of use without stickiness. , Useful as a skin softening cosmetic. Therefore, it is possible to continuously and safely protect the skin from dryness and roughness even in a low temperature or low humidity atmosphere, or even under conditions where a detergent or solvent is excessively used. Further, it is excellent in the effect of suppressing the generation of wrinkles and eliminating wrinkles, and has a good feeling in use, and is particularly useful as a wrinkle improving agent and an antiaging cosmetic.

[0067]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the invention is limited thereto.

Example 1 The following compounds (1) to (26) were used as the guanidine derivative or its acid addition salt, and the effect of improving wrinkles was evaluated.

[0069]

Embedded image

[0070]

Embedded image

[0071]

Embedded image

[0072]

Embedded image

[0073]

Embedded image

[Formation in hairless mice by UVB irradiation
The present skin cosmetic preparation (I) for shirred wrinkles]: (1) Hairless mouse (HR / ICR, 9 weeks from the start of the experiment)
Age, use 6 Toshiba Health Line lamps 20SE
VB light was irradiated 3 times a week. The amount of energy is TOKYO
UV-Radiometer made by OPTICAL
It was measured using UVR-305 / 365D. 1 time light
Irradiation is 1 MED or less, 0.28 mW / cm ^TwoEnergy of
-The amount was set to 65 mJ. Irradiation period is 20 weeks, hairless
After confirming that wrinkles are formed on the back of the mouse,
Guanidine derivative or its acid addition salt
Water / ethanol containing (concentration 4%) = 50 / 50vo
l% water-containing ethanol solution 100 μl each 5 times a week 6
Continued to apply for a week. Water / ethanol as control
= 100 / μl of 50/50 vol% hydrous ethanol
It was applied in the same manner as the sample. After application, wrinkle the meat
It was evaluated by eyes according to the following criteria (wrinkle index). The result
It shows in Table 1.

(Wrinkle index) 1: Wrinkles disappear completely 2: Do not know if there are wrinkles 3: There are some wrinkles 4: Very wrinkles

(2) Furthermore, in order to analyze the details of wrinkles,
For each mouse, a skin replica having a diameter of 14 mm was collected from one place by using Hydrophilic Exaflex hydrophilic vinyl silicone impression material. This replica was placed in a horizontal state and irradiated with light from the direction of 30 degrees, and the ratio of the shadow formed by wrinkles was obtained as an area ratio using an image analyzer. The results are shown in Table 1.

[0077]

[Table 1]

As is clear from Table 1, the wrinkles formed on the back of the hairless mouse show guanidine derivatives (1) to (2).
It can be eliminated by applying 6).

Example 2 [Action of skin cosmetics of the present invention on wrinkles formed in hairless mice by UVB irradiation (II)] As a guanidine derivative or an acid addition salt thereof, the same as in Example 1 (concentration 4%) The wrinkle index and the image analysis area ratio were determined in the same manner as in Example 1 except that the concentration of the synthetic sphingosine derivative shown in Table 2 was 0.5%. The results are shown in Table 3.

[0080]

[Table 2]

[0081]

[Table 3]

Example 3 A cream having the following formulation was produced by a conventional method.

[0083]

[Table 4] (Components) (% by weight) Stearic acid 2.0 Squalane 2.0 Cholesterol 3.0 Olive oil 1.0 Cetanol 7.0 Jojoba oil 2.0 2-Hexadecylphosphoric acid arginine salt 2.0 Polyoxy Ethylene (40EO) hydrogenated castor oil 0.5 glycerin 10.0 1,3-butylene glycol 5.0 2-guanidinocyclohexanecarboxylic acid 2.0 guanidine derivative (compound (7) in Example 1) 1.0 succinic acid 1.0 Purified water Balance meter 100.0

The cream of the above formulation was subjected to a sensory test by a specialized panelist, and as a result, it exhibited an excellent effect of imparting flexibility to the skin and an effect of improving wrinkles, and it was not sticky and had a good feeling in use.

Example 4 An emulsion having the following formulation was produced by a conventional method.

[0086]

[Table 5] (Components) (wt%) Palmitic acid 0.5 Olive oil 2.0 Cetanol 1.0 Jojoba oil 5.0 Monohexadecylphosphoric acid sodium salt 2.0 Sorbitan monostearate 0.5 Glycerin 15.0 Ethanol 5.0 Guanidine derivative (Compound (12) in Example 1) 4.0 Guanidin derivative (Compound (8) in Example 1) 2.0 Lactic acid 2.0 Purified water Balance meter 100.0

The emulsion of the above formulation was subjected to a sensory test by a specialized panelist, and as a result, it exhibited an excellent effect of imparting flexibility to the skin and an effect of improving wrinkles, and it was not sticky and had a good feeling in use.

Example 5 A lotion having the following formulation was produced by a conventional method.

[0089]

[Table 6] (Components) (wt%) Guanidine derivative (Compound (10) in Example 1) 7.0 Guanidine derivative (Compound (11) in Example 1) 5.0 Citric acid 1.0 86% Glycerin 15.0 Polyethylene glycol (PEG1500; Sanyo Chemical Co., Ltd.) 2.0 Hyaluronic acid 0.05 Dipropylene glycol 5.0 Purified water Balance meter 100.0

As a result of a sensory test conducted by a professional panelist on the lotion having the above-mentioned formulation, it showed an excellent effect of imparting flexibility to the skin and an effect of improving wrinkles, and it was not sticky and had a good feeling in use.

Example 6 A pack formulation having the following formulation was produced by a conventional method.

[0092]

[Table 7] (Components) (wt%) Polyvinyl alcohol 11.7 (Gothenol EG-30; manufactured by Nippon Synthetic Chemical Industry Co., Ltd.) 1,3-butylene glycol 2.5 glycerin 1.0 titanium oxide 1.5 guanidine derivative ( Compound (1) in Example 1 1.0 Guanidine derivative (Compound (4) in Example 1) 1.0 Guanidine derivative (Compound (16) in Example 1) 2.0 Tartaric acid 7.0 Purification Water balance meter 100.0

As a result of a sensory test conducted by a professional panelist on the packs having the above-mentioned formulation, the packs showed an excellent effect of imparting flexibility to the skin and an effect of improving wrinkles, and there was no stickiness and a good feeling in use.

Example 7 A gel having the following formulation was produced by a conventional method.

[0095]

[Table 8] (Components) (wt%) Polyacrylic acid (Carbopol; manufactured by Goodrich) 0.5 Potassium hydroxide 0.15 Glucum 10.0 10.0 86% Glycerin 10.0 Glycine betaine 3.0 Guanidine derivative ( Compound (3) in Example 1 0.5 Guanidine derivative (Compound (8) in Example 1) 1.0 Guanidine derivative (Compound (14) in Example 1) 0.5 Succinic acid 1.5 Purified water balance meter 100.0

The gel of the above formulation was subjected to a sensory test by a specialized panelist, and as a result, it exhibited an excellent effect of imparting flexibility to the skin and an effect of improving wrinkles, and it was not sticky and had a good feeling in use.

Example 8 A lotion having the following formulation was produced by a conventional method.

[0098]

Table 9 (Component) (wt%) Guanidine derivative (Compound (9) in Example 1) 3.0 Guanidine derivative (Compound (13) in Example 1) 2.0 Guanidine derivative (In Example 1) , Acetate of compound (7)) 2.0 86% glycerin 15.0 dipropylene glycol 5.0 purified water balance meter 100.0

As a result of a sensory test conducted by a professional panelist on the lotion having the above-mentioned formulation, it showed an excellent effect of imparting flexibility to the skin and an effect of improving wrinkles, and there was no stickiness and a good feeling in use.

Example 9 Cream A cream having the formulation shown below was produced by a conventional method.

[0101]

[Table 10] (Components) (wt%) Stearic acid 2.00 Squalane 2.00 Cholesterol 3.00 Olive oil 1.00 Cetanol 7.00 Jojoba oil 2.00 2-Hexadecylphosphoric acid Arginic acid 2.00 Polyoxy Ethylene (40EO) hydrogenated castor oil 0.50 glycerin 10.00 1,3-butylene glycol 5.00 guanidine derivative (compound (1) in Example 1) 5.00 guanidine derivative (compound (4 in Example 1) )) 5.00 Succinic acid 1.00 Purified water Balance meter 100.00

The cream of the above formulation was subjected to a sensory test by a professional panelist, and as a result, it exhibited an excellent effect of imparting flexibility to the skin and an effect of improving wrinkles, and it was not sticky and had a good feeling in use.

Example 10 Gel A gel having the following formulation was produced by a conventional method.

[0104]

Table 11 (Components) (wt%) Polyoxyethylene isocetyl ether (20EO) 1.00 Sodium polyoxyethylene trialkylphosphate (10EO) 1.00 Sorbitol 0.50 1,3-Propanediol 0.50 Xanthan gum 0.50 Tuberose polysaccharide 3.00 Carboxyvinyl polymer (Carbopol 940, Goodrich) 0.20 Potassium hydroxide 0.90 Allantoin 0.10 Zinc sulfocarbonate 0.20 Guanidine derivative (Example 1) Medium, compound (19)) 10.00 Guanidine derivative (Compound (21) in Example 1) 3.00 Ethanol 20.00 Preservative proper amount Perfume proper amount Purified water Balance meter 100.00

The gel of the above formulation was subjected to a sensory test by a professional panelist, and as a result, it exhibited an excellent effect of imparting flexibility to the skin and an effect of improving wrinkles, and it was not sticky and had a good feeling in use.

Example 11 Gel A gel having the following formulation was produced by a conventional method.

[0107]

[Table 12] (Components) (% by weight) Silicone composition (XSG-16, manufactured by Shin-Etsu Chemical Co., Ltd.) 5.00 Methyl polysiloxane (KF96A-6cs, manufactured by Shin-Etsu Chemical Co., Ltd.) 15.00 Methyl polysiloxane (SH244, Toray)・ Dow Corning Co., Ltd.) 5.00 Methyl polysiloxane methyl (polyoxyethylene) Siloxane Copolymer (SH3771C, Toray Dow Corning Co., Ltd.) 2.00 Methyl polysiloxane methyl (polyoxyethylene) Siloxane Copolymer (SH3775C, Toray Dow Corning Co., Ltd.) 1.00 Methylcellulose 0.20 Hydroxyethylcellulose Hydroxypropyltrimethylammonium chloride ether (Cathello H-60, Kao Corporation) 0.02 Acetic acid dl-α-tocopherol 0.05 Glycyrrhetinic acid iso Stearyl 0.10 Isopropylmethylphenol 0.10 Zinc flower (In Example 1, Compound (1)) .50 guanidine derivative 7.00 (in Example 2, Compound (27)) sphingosine derivative 0.50 Ethanol 5.00 Preservative qs Perfume qs Purified water Balance Total 100.00

The gel of the above formulation was subjected to a sensory test by a professional panelist, and as a result, it exhibited an excellent effect of imparting flexibility to the skin and an effect of improving wrinkles, and it was not sticky and had a good feeling in use.

Example 12 Lotion A lotion having the formulation shown below was produced by a conventional method.

[0110]

[Table 13] (Components) (% by weight) Arginine 0.40 Lysine 0.40 Polyoxyethylene hydrogenated castor oil (40EO) 1.50 Methyl polysiloxane methyl (polyoxyethylene) siloxane copolymer (SH3775C, Toray 0.60 Glycerin 5.00 Glycine betaine 0.20 Trisodium citrate 0.90 Citric acid 0.40 Urea 0.50 ε-Aminocaproic acid 0.10 Guanidine derivative (compound (in Example 1) 1)) 5.00 Sphingosine derivative (Compound (27) in Example 2) 0.50 Ethanol 5.00 Preservative proper amount Perfume proper amount Purified water Balance meter 100.00

As a result of a sensory test of a lotion having the above-mentioned formulation by a specialized panelist, it was found that the skin lotion exhibited an excellent effect of imparting flexibility to the skin and an effect of improving wrinkles, and there was no stickiness and a good feeling in use.

Example 13 Lotion A lotion having the formulation shown below was produced by a conventional method.

[0113]

[Table 14] (Components) (wt%) triethanolamine 0.40 potassium hydroxide 0.20 polyoxyethylene isocetyl ether (20EO) 0.30 polyoxyethylene oleyl ether sodium phosphate (8EO) 0.30 poly Sodium oxyethylene dialkyl phosphate (10EO) 0.10 Polyethylene glycol 1500 2.00 Polyoxyethylene methyl glucoside (10EO) 1.50 Dipropylene glycol 0.50 Disodium hydrogen phosphate 0.50 Succinic acid 0.30 Guanidine derivative (Compound (1) in Example 1) 7.00 Sphingosine derivative (Compound (30) in Example 2) 0.50 Ethanol 10.00 Preservative proper amount Perfume proper amount Purified water Balance meter 100.00

As a result of a sensory test conducted by a professional panelist on the lotion having the above-mentioned formulation, it showed an excellent effect of imparting flexibility to the skin and an effect of improving wrinkles, and there was no stickiness and a good feeling in use.

Example 14 Packing Agent A packing having the following formulation was produced by a conventional method.

[0116]

[Table 15] (Components) (% by weight) Polyvinyl alcohol (Gosenol EG-30, manufactured by Nippon Synthetic Chemical Industry) 15.00 Aqueous carboxymethyl chitin solution (chitin liquid HV-10, manufactured by Ichimaru Falcos) 5.00 Triglucopolysaccharide ( Pullulan PI-20, manufactured by Hayashibara) 0.50 Xanthan gum 0.50 Sodium carboxymethyl cellulose 0.50 Titanium oxide 15.00 Aluminum magnesium silicate 1.00 1-Isostearoyl-3-myristoyl-glycerol 1.00 Diglycerin 1. 50 Polyoxyethylene isocetyl ether (20EO) 1.00 Guanidine derivative (Compound (14) in Example 1, 7.00 Sphingosine derivative (Compound (27) 0.70, Ethanol 5.00 in Example 2) Preservative Suitable amount Fragrance Suitable amount Purified water Balance meter 100.00

As a result of a sensory test conducted by a professional panelist on the pack having the above-mentioned formulation, it was found to have an excellent effect of imparting flexibility to the skin and an effect of improving wrinkles, and there was no stickiness and a good usability.

Example 15 Emulsion An emulsion having the formulation shown below was produced by a conventional method.

[0119]

[Table 16] (Components) (% by weight) Palmitic acid 0.50 Olive oil 2.00 Cetanol 1.00 Jojoba oil 5.00 Monohexadecylphosphate sodium salt 2.00 Sorbitan monostearate 0.50 Glycerin 15.00 Ethanol 5.00 Guanidine derivative (Compound (2) in Example 1) 10.00 Sphingosine derivative (Compound (27) in Example 2) 0.30 Lactic acid 2.00 Purified water Balance meter 100.00

The emulsion of the above formulation was subjected to a sensory test by a specialized panelist, and as a result, it exhibited an excellent effect of imparting flexibility to the skin and an effect of improving wrinkles, and it was not sticky and had a good feeling in use.

Example 16 Emulsion An emulsion having the formulation shown below was produced by a conventional method.

[0122]

Table 17 (Components) (wt%) N- (3-hexadecyloxy-2-hydroxypropyl) -N-2-hydroxyethyl decanamide 0.50 N- (3-hexadecyloxy-2-hydroxy Propyl) -N-2-hydroxyethylhexadecanamide 1.00 N- (3-tetradecyloxy-2-hydroxypropyl) -N-2-hydroxyethyldecanamid 0.50 Polyoxyethylene hydrogenated castor oil ( 10EO) 1.00 Methyl polysiloxane / methyl (polyoxyethylene) siloxane copolymer (SH3775C, manufactured by Toray Dow Corning) 1.00 Sorbitan monostearate 0.20 Stearoylmethyl taurine sodium 0.50 Cholesterol 0.80 Cholesterol isostearate 0.20 Alkenyl succinate monocholesteryl 0.8 Stearic acid 0.20 Palmitic acid 0.30 Myristic acid 0.10 Pentyl glycol dicaprate 4.00 Methyl polysiloxane (KF96A-500cs, Shin-Etsu Chemical Co., Ltd.) 2.00 Isostearyl alcohol 1.20 Cetyl alcohol 1.00 Glycerin 3.50 Lactic acid 0.20 Sodium lactate 0.30 Guanidine derivative (Compound (5) in Example 1) 5.00 Sphingosine derivative (Compound (27) in Example 2) 0.30 Preservative Suitable amount Perfume Suitable amount Purification Water balance meter 100.00

The emulsion of the above formulation was subjected to a sensory test by a specialized panelist, and as a result, it exhibited an excellent effect of imparting flexibility to the skin and an effect of improving wrinkles, and it was not sticky and had a good feeling in use.

Example 17 A poultice of the formulation shown below was produced by a conventional method.

[0125]

Table 18 (Components) (wt%) α-monoisostearyl glycerether 1.00 Neocapric acid pentyl glycol methyl polysiloxane 4.00 Glycerin 35.00 Purified water 15.80 Sodium polyacrylate 5.50 Aluminum potassium sulfate 1.00 Polyacrylic acid aqueous solution (10%) 15.00 Light anhydrous silicic acid 2.00 Guanidine derivative (Compound (16) in Example 1) 10.00 Sphingosine derivative (Compound (27) in Example 2) 0.20 Purified water Balance meter 100.00

As a result of a sensory test of a poultice of the above-mentioned formulation by a specialized panelist, it showed an excellent effect of imparting flexibility to the skin and an effect of improving wrinkles, and there was no stickiness and a good feeling in use.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Reference number within the agency FI Technical display location C07H 5/04 C07H 5/04 (72) Inventor Yama ▲ saki ▼ Seiji Fumika Sumida-ku, Tokyo 2 -1-3 Inside Kao Institute of Stock Companies (72) Inventor Yuzo Kawada 2-1-3 Fumika, Sumida-ku, Tokyo 3-1-3 Inside Institute of Kao Corporation (72) Akira Yamamuro 2606 Kao, Kaiga-cho, Haga-gun, Tochigi Prefecture Kao In stock company research institute (72) Inventor Minoru Nagai 2606 Akabane, Kaicho, Haga-gun, Tochigi Prefecture Kao Stock Company research institute (72) Inventor Toshiya Ono 2606 Akabane, Kai-cho, Haga-gun, Tochigi Prefecture Kao Stock Company research institute

Claims (10)

[Claims] 1. The following general formula (1): (In the formula, R ¹ is a linear or branched hydrocarbon group, or an aromatic ring group which may have a substituent, an aralkyl group,
A guanidine derivative represented by a cycloalkyl group or an oxacycloalkyl group, and R ² represents a hydrogen atom or a linear or branched hydrocarbon group, or an acid addition salt thereof, for external skin use. Agent. 2. The external preparation for skin according to claim 1, which contains 0.001 to 50% by weight of a guanidine derivative or an acid addition salt thereof. 3. The following general formula (2): (In the formula, R ⁴ represents a straight-chain, branched-chain or cyclic saturated or unsaturated hydrocarbon group having 4 to 40 carbon atoms. R ⁵ , R ⁶ and R
⁷ , R ⁸ and R ⁹ are each a hydrogen atom or 1 or 2
The above hydroxyl group represents a hydrocarbon group having 1 to 10 carbon atoms which may be substituted, and X and Y represent an alkyl group having 1 to 6 carbon atoms which may have a hydrogen atom or an oxygen atom). The external skin preparation according to claim 1 or 2, which comprises the represented synthetic sphingosine derivative. 4. A synthetic sphingosine derivative of 0.000
The external preparation for skin according to claim 3, which contains 1 to 10% by weight. 5. The external preparation for skin according to claim 1, further comprising an organic acid or its ester. 6. An organic acid or its ester is added to 0.001
The external preparation for skin according to any one of claims 1 to 5, which comprises -30% by weight. 7. The external skin preparation according to claim 5, wherein the organic acid is a dicarboxylic acid. 8. The skin external preparation according to claim 1, which is a skin softening cosmetic. 9. The external preparation for skin according to claim 1, which is an antiaging cosmetic. 10. The external preparation for skin according to claim 1, which is a wrinkle improving agent.