JP5014592B2 - Inadequate keratinization inhibitor, pore reducing agent, rough skin prevention / improving agent - Google Patents

Description

  The present invention provides a keratinization inhibitor that suppresses keratinization caused by sebum, suppresses keratinization due to a stimulating component in sebum around pores, keeps the skin around pores normal, and a mortar-like structure of pores The present invention relates to a pore-reducing agent that suppresses the noticeability of skin, and an agent that prevents and improves rough skin caused by unsaturated fatty acids.

  In recent years, especially for young women, worries about the conspicuous pores have been increasing, and a composition for external application to the skin has been required. However, the mechanism by which pores are conspicuous is not clear, and countermeasures by removing astringent lotion and square plugs are common. Or they often improve the appearance with a foundation. However, for example, astringent lotion is intended to tighten the skin, and is due to the action of temporarily lowering the skin surface temperature with alcohol or coagulating proteins with organic acid or the like. Therefore, since the skin is temporarily tightened, the load on the skin is large, and it is not a fundamental solution for conspicuous pores, and the effect is not sufficient.

  On the other hand, although there are reports that glycolic acid and ascorbic acid derivatives have a pore-reducing effect (for example, see Non-Patent Document 1), there are many unclear points such as the mechanism of action and the degree of effect.

  In addition, horn plug removal is a method of physically removing horn plugs clogged in pores. For example, horn plug removal agent containing a polymer compound having a salt-forming group (see, for example, Patent Document 1), water. Cosmetics containing insoluble cyclodextrin polymer (for example, see Patent Document 2), cosmetics for removing horn plugs containing 50% by mass or more of oil having a viscosity of 5 to 80 mPa · s / 25 ° C. (for example, Patent Document 3) For example). In such a method of removing the horn plug, the physical force may damage the skin, and the side effect on the skin sometimes becomes a problem. In addition, the effect is temporary, and the plug is immediately regenerated, and when the plug is removed, the pores become conversely large, and the effect is not necessarily sufficient.

In order to develop a composition for external use on the skin that improves the conspicuousness of pores, the present inventors have conducted intensive studies on the conspicuous mechanism of pores,
(1) The concavity around the pores is recognizable as a pore, and this part is conspicuous if it is wide,
(2) Furthermore, the stratum corneum of this mortar-like part is in a keratinized state (the nucleus that should have disappeared remains),
(3) People with conspicuous pores have a large amount of sebum, especially unsaturated fatty acids,
(4) This unsaturated fatty acid can cause keratinization,
(5) The conspicuous pores were found to be likely due to the unsaturated fatty acids in the sebum, and were announced at the 102nd Annual Meeting of the Japanese Dermatological Association (see Non-Patent Document 2).

  From the above, it has been clarified that the keratinization caused by sebum is partly responsible for the conspicuous mechanism of pores. Furthermore, it was clarified that the conspicuousness of pores is improved by improving the keratinization.

  Furthermore, as a result of searching for a drug having the effect of inhibiting keratinization and reducing pores, it was found that an excitatory cell receptor antagonist or an inhibitory cell receptor agonist has these functions (Patent Literature). As a representative example of these, the former antagonists include D-glutamic acid and TNP-ATP. Examples of the latter agonist include glycine, β-alanine, GABA, serine, taurine and the like.

  However, conventional compounds are insufficient in effect such as keratinization suppression effect, pore reduction effect, skin roughness prevention / improvement effect, etc., and have sensory irritation, and the composition is limited when applied to an external composition for skin, etc. None of them are sufficiently satisfactory as a keratinization inhibitor, a pore-reducing agent, or a rough skin prevention / improving agent, and the development of a more excellent compound has been desired.

Japanese Patent Laid-Open No. 5-97627 JP-A-5-105619 Japanese Patent Laid-Open No. 2002-241260 Japanese Patent Application No. 2002-153457 Yazawa et al., Fragrance Journal, 2002, Volume 30, Issue 2, p54-58 Iida et al., 102nd Annual Meeting of the Japanese Dermatological Association, Abstract, 2003, 103, p846

  The present invention has been made in view of the above circumstances, and its purpose is to have functions such as suppression of keratinization, reduction of pores, prevention and improvement of rough skin, and no safety problems such as sensory stimulation. It is to provide an agent for suppressing keratinization, a pore reducing agent, or a rough skin preventing / improving agent. The external composition for skin containing the compound having the function is excellent in the function, has no safety problems such as sensory stimulation, and has high safety.

  In order to solve the above-mentioned problems, the present inventors have conducted a search for a compound having an inhibitory effect on keratinization by unsaturated fatty acids based on the above findings, and as a result, specific α-amino acid derivatives and salts thereof have the above-mentioned action. The present invention has been completed by finding that the above-mentioned problems can be solved by having high safety without sensory stimulation.

  That is, the present invention provides an keratinization inhibitor, pore reducing agent, or rough skin prevention comprising one or more compounds selected from the group consisting of α-amino acid derivatives represented by the following general formula (1) and salts thereof.・ Improvement agent.

(In General Formula (1), R ₁ represents a hydrogen atom or a CH ₃ group, and R ₂ represents a hydrogen atom, a CH ₃ group, or a CH ₂ OH group. However, when R ₁ is a CH ₃ group, R ₂ Represents a hydrogen atom or a CH ₃ group, wherein R ₃ and R ₄ are each independently a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, an allyl group, a carbobenzyloxy group, an acetyl group, represented by the following general formula (2). Or a group represented by the following general formula (3), provided that when one of R ₃ and R ₄ is a carbobenzyloxy group, each of R ₁ and R ₂ is a hydrogen atom or Each of them is a CH ₃ group, and when R ₁ and R ₂ are both hydrogen atoms and one of R ₃ and R ₄ is a hydrogen atom, one (the other) is a carbobenzyloxy group or a group represented by the formula (2) .R ₁ and one _{R 2} If If is or _{R 1} whereas a hydrogen atom (other) is CH ₃ groups are _{R 2} is hydrogen atom is a _CH 2 OH group, one of _{R 3} and _{R 4} are acetyl group, the following general formula (2 Or a group represented by the following general formula (3).)

(In General Formula (2), X ₁ , X ₂ and X ₃ are each independently an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a hydroxyl group, an amino group, or 1 to 4 carbon atoms. Represents any one of an alkylamino group, a fluorine atom and a trifluoromethyl group, n, m and p each independently represents an integer of 0 to 3, and k and q each independently represents an integer of 0 to 2)

(In general formula (3), X ₁ , X ₂ , X ₃ , k, n, m, and p are the same as in general formula (2).)

In the general formula (1), R ₁ and R ₂ are preferably both hydrogen atoms.

In the general formula (1), R ₁ is preferably a hydrogen atom and R ₂ is preferably a CH ₂ OH group.

In the general formula (1), it is preferable that _one of R ₁ and R ₂ is a hydrogen atom and the other is a CH ₃ group.

In the general formula (1), it is preferable that R ₁ and R ₂ are both CH ₃ groups.

In the general formula (1), it is preferable that R ₁ and R ₂ are both hydrogen atoms or CH ₃ groups, and one of R ₃ and R ₄ is a carbobenzyloxy group.

In the general formula (1), at _{least one} of R ₁ and R ₂ is a CH ₃ group or R ₁ is a hydrogen atom and R ₂ is a CH ₂ OH group, and one of R ₃ and R ₄ is acetyl. It is preferably a group.

In the general formula (1), it is preferable that one of R ₃ and R ₄ is a cyclohexanecarbonyl group.

In the general formula (1), it is preferable that R ₁ and R ₂ are both hydrogen atoms, one of R ₃ and R ₄ is a methyl group, and one (the other) is a benzoyl group. In the general formula (1), at _{least one} of R ₁ and R ₂ is a CH ₃ group, or R ₁ is a hydrogen atom and R ₂ is a CH ₂ OH group, and either one of R ₃ and R ₄ is A benzoyl group or a phenylacetyl group is preferred. In the general formula (1), it is preferable that R ₁ and R ₂ are both hydrogen atoms or CH ₃ groups, and any one of R ₃ and R ₄ is a hydrogen atom or a methyl group, The other is preferably a carbobenzyloxy group.

In the general formula (1), either one or both of R ₁ and R ₂ is a CH ₃ group, or R ₁ is a hydrogen atom and R ₂ is a CH ₂ OH group, and any one of R ₃ and R ₄ One is preferably a hydrogen atom or a methyl group, and the other (the other) is preferably an acetyl group, a cyclohexanecarbonyl group, a benzoyl group or a phenylacetyl group.

  The α-amino acid derivative represented by the general formula (1) is (N-methyl) methylalanine, N-carbobenzyloxyglycine, N-carbobenzyloxysarcosine, N-carbobenzyloxymethylalanine, N-acetyl-L. -Alanine, N-acetyl-DL-alanine, N-acetyl-D-alanine, N-acetyl-L-serine, N-acetyl-DL-serine, N-acetyl-D-serine, N-acetylsarcosine, N- Acetylmethylalanine, N-cyclohexanecarbonylglycine, N-cyclohexanecarbonylsarcosine, N-cyclohexanecarbonyl-L-alanine, N-cyclohexanecarbonyl-DL-alanine, N-cyclohexanecarbonyl-D-alanine, N-cyclohexanecarbonylmethylalanine, N- Chrohexanecarbonyl-L-serine, N-cyclohexanecarbonyl-DL-serine, N-cyclohexanecarbonyl-D-serine, N-benzoyl-L-serine, N-benzoyl-DL-serine, N-benzoyl-L-serine, N-benzoyl-L-alanine, N-benzoyl-DL-alanine, N-benzoyl-D-alanine, N-benzoylmethylalanine, N-benzoylsarcosine, N-phenylacetyl-L-serine, N-phenylacetyl-DL -Serine, N-phenylacetyl-D-serine, N-phenylacetyl-L-alanine, N-phenylacetyl-DL-alanine, N-phenylacetyl-D-alanine, N-phenylacetylmethylalanine, N-phenylacetyl Preferably any of sarcosine .

  The keratinization inhibitor, pore reducing agent or rough skin preventing / improving agent of the present invention can be applied to an external preparation for skin.

  According to the present invention, a highly safe, keratinization inhibitor that suppresses keratinization caused by sebum, suppresses keratinization due to stimulating components in sebum around pores, and normalizes skin around pores. A pore-reducing agent that maintains and suppresses the conspicuousness of the mortar-like structure of pores, and an agent for preventing and improving rough skin that prevents and improves rough skin caused by unsaturated fatty acids. In addition, these keratinization suppression, pore reduction, skin roughening prevention / improving agents can be applied to external preparations for skin. A composition for external use with skin is obtained.

  Hereinafter, the present invention will be described in detail.

  In the present invention, one or more compounds selected from the group consisting of α-amino acid derivatives represented by the following general formula (1) and salts thereof are used.

(In General Formula (1), R ₁ represents a hydrogen atom or a CH ₃ group, and R ₂ represents a hydrogen atom, a CH ₃ group, or a CH ₂ OH group. However, when R ₁ is a CH ₃ group, R ₂ Represents a hydrogen atom or a CH ₃ group, wherein R ₃ and R ₄ are each independently a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, an allyl group, a carbobenzyloxy group, an acetyl group, represented by the following general formula (2). Or a group represented by the following general formula (3), provided that when one of R ₃ and R ₄ is a carbobenzyloxy group, each of R ₁ and R ₂ is a hydrogen atom or Each of them is a CH ₃ group, and when R ₁ and R ₂ are both hydrogen atoms and one of R ₃ and R ₄ is a hydrogen atom, one (the other) is a carbobenzyloxy group or a group represented by the formula (2) .R ₁ and one _{R 2} If If is or _{R 1} whereas a hydrogen atom (other) is CH ₃ groups are _{R 2} is hydrogen atom is a _CH 2 OH group, one of _{R 3} and _{R 4} are acetyl group, the following general formula (2 Or a group represented by the following general formula (3).)

(In General Formula (2), X ₁ , X ₂ and X ₃ are each independently an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a hydroxyl group, an amino group, or 1 to 4 carbon atoms. Represents any one of an alkylamino group, a fluorine atom and a trifluoromethyl group, n, m and p each independently represents an integer of 0 to 3, and k and q each independently represents an integer of 0 to 2)

(In general formula (3), X ₁ , X ₂ , X ₃ , k, n, m, and p are the same as in general formula (2).)

  Hereinafter, the α-amino acid derivative represented by the general formula (1) according to the present invention will be described.

In General Formula (1), R ₁ represents a hydrogen atom or a CH ₃ group, and R ₂ represents a hydrogen atom, a CH ₃ group, or a CH ₂ OH group. However, when R ₁ is a CH ₃ group, R ₂ represents a hydrogen atom or a CH ₃ group. The present invention is when _{R 1} and _{R 2} are each a hydrogen atom, it is glycine derivatives corresponding to _{R 1} or _{R 2,} either _{R 1} or _{R 2} in CH ₃ group, whereas (other) is When it is a hydrogen atom, it becomes a corresponding alanine derivative, when R ₁ is a hydrogen atom and R ₂ is a CH ₂ OH group, it becomes a corresponding serine derivative, and when both R ₁ and R ₂ are CH ₃ groups, The corresponding methylalanine derivative is obtained. Since all the effects of the alanine derivative are good, any of D-form, L-form, and DL-form (DL mixture) may be used, and the mixing ratio of the DL-form (DL mixture) is not limited. Since the effects of the serine derivative are all good, any of D-form, L-form and DL-form (DL mixture) may be used, and the DL-form (DL mixture) may be mixed at any ratio.

R ₃ and R ₄ are each independently a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, an allyl group, a carbobenzyloxy group, an acetyl group, a group represented by the general formula (2), or the general formula (3). Any one of the groups represented by

Further, when R ₁ and R ₂ are both hydrogen atoms (glycine derivatives) and one of R ₃ and R ₄ is a hydrogen atom, one (the other) of R ₃ and R ₄ is a carbobenzyloxy group or It is group represented by the said General formula (2). In this case, any combination of R ₃ and R ₄ can be used as long as both are other than hydrogen atoms.

When R ₁ and R ₂ are both hydrogen atoms (glycine derivatives) and both are CH ₃ groups (methylalanine derivatives), one of R ₃ and R ₄ can be a carbobenzyloxy group. When _one of R ₁ and R ₂ is a hydrogen atom and one (the other) is a CH ₃ group (alanine derivative) and when R ₁ is a hydrogen atom and R ₂ is a CH ₂ OH group (serine derivative), R ₃ And one of R ₄ is not a carbobenzyloxy group.

Further, when _one of R ₁ and R ₂ is a hydrogen atom and one (the other) is a CH ₃ group (alanine derivative), or R ₁ is a hydrogen atom and R ₂ is a CH ₂ OH group (serine derivative), One of R ₃ and R ₄ is an acetyl group, a group represented by the general formula (2), or a group represented by the general formula (3) (N-acyl-α-amino acid derivative). .

When R ₁ and R ₂ are both CH ₃ groups (methylalanine derivatives), any combination can be taken.

In the α-amino acid derivative of the present invention, since the effect of the present invention is good, one of R ₃ and R _{4 is} any one of a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, and an allyl group. preferable. Furthermore, since an effect is favorable, it is most preferable that they are a hydrogen atom or a methyl group.

When one of R ₃ and R ₄ is an alkyl group having 1 to 3 carbon atoms, specific examples include a methyl group, an ethyl group, an n-propyl group, and an iso-propyl group. In the α-amino acid derivative of the present invention, a methyl group is preferable because of good effects.

When one of R ₃ and R ₄ is an alkyl group having 1 to 3 carbon atoms, as described above, one (the other) is preferable because the effect is good in any case within the scope of the present invention. When both R ₁ and R ₂ are CH ₃ groups (methylalanine derivatives), it is most preferable that one (the other) of R ₃ and R ₄ is a hydrogen atom.

  A preferable α-amino acid derivative corresponding to this is (N-methyl) methylalanine.

When one of R ₃ and R ₄ is an allyl group, either one (the other) is within the scope of the present invention as described above, and thus any case is preferable because the effect is good.

When one of R ₃ and R ₄ is a carbobenzyloxy group, as described above, R ₁ and R ₂ are both hydrogen atoms (glycine derivatives) or both are CH ₃ groups (methylalanine derivatives). In that case, either one of R ₃ and R ₄ (the other) may be within the scope of the present invention, but since the effects of the present invention are good, a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, allyl It is preferably a group. Furthermore, since an effect is favorable, it is preferable that they are a hydrogen atom or a methyl group.

  Specific preferred α-amino acid derivatives corresponding thereto include N-carbobenzyloxyglycine, N-carbobenzyloxysarcosine, (N-carbobenzyloxy) methylalanine, and (N-carbobenzyloxy-N-methyl). ) Methyl alanine.

When one of R ₃ and R ₄ is an acetyl group, when both R ₁ and R ₂ are hydrogen atoms (glycine derivatives), one (the other) is an alkyl group or an allyl group having 1 to 3 carbon atoms. As described above, it is not a hydrogen atom. In that case, one (the other) is preferably a methyl group because the effect is good.

  Specific examples of the preferable α-amino acid derivative corresponding to this include N-acetylsarcosine (N-acetyl-N-methylglycine).

When one of R ₃ and R ₄ is an acetyl group, one or both of R ₁ and R ₂ are CH ₃ groups (alanine derivatives and methylalanine derivatives) or R ₁ is a hydrogen atom and R ₂ is a CH ₂ OH group ( In the case of a serine derivative), one (the other) is a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or an allyl group. Since the effect of this invention is favorable, it is preferable that they are a hydrogen atom or a methyl group. Most preferred is a hydrogen atom.

  Specific preferred α-amino acid derivatives corresponding thereto include N-acetylalanine, N-acetyl-N-methylalanine, (N-acetyl) methylalanine, (N-acetyl-N-methyl) methylalanine, Examples include N-acetylserine and N-acetyl-N-methylserine. Most preferred are N-acetylalanine, (N-acetyl) methylalanine, and N-acetylserine.

In the general formula (2), X ₁ , X ₂ and X ₃ are each independently an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a hydroxyl group, an amino group, or 1 to 4 carbon atoms. It represents either a mono- or dialkylamino group, a fluorine atom, or a trifluoromethyl group. Specific examples of the alkyl group having 1 to 4 carbon atoms include methyl group, ethyl group, n-propyl group, iso-propyl group, n-butyl group, iso-butyl group, tert-butyl group, and 1-methyl group. A propyl group is mentioned. Specific examples of the alkoxy group having 1 to 4 carbon atoms include methoxy group, ethoxy group, n-propyloxy group, iso-propyloxy group, n-butoxy group, iso-butoxy group, tert-butoxy group, 2-methylpropoxy group. A loxy group is mentioned.

  Examples of the mono- or dialkylamino group having 1 to 4 carbon atoms include N-methylamino group, N-ethylamino group, Nn-propylamino group, N-iso-propylamino group, Nn-butylamino group, N-iso-butylamino group, N-tert-butylamino group, N- (1-methylpropyl) amino group, N, N-dimethylamino group, N-ethyl-N-methylamino group, N-methyl-N -N-propylamino group, N-methyl-N-iso-propylamino group, Nn-butyl-N-methylamino group, N-iso-butyl-N-methylamino group, N-tert-butyl-N -Methylamino group, N- (1-methylpropyl) -N-methylamino group, N-ethyl-N-methylamino group, N, N-diethylamino group, N-ethyl-Nn-propylamino group, N Ethyl-N-iso-propylamino group, Nn-butyl-N-ethylamino group, N-iso-butyl-N-ethylamino group, N-tert-butyl-N-ethylamino group, N-ethyl- N- (1-methylpropyl) amino group, N-methyl-Nn-propylamino group, N-ethyl-Nn-propylamino group, N, N-di (n-propyl) amino group, N- n-propyl-N-iso-propylamino group, Nn-butyl-Nn-propylamino group, N-iso-butyl-Nn-propylamino group, N-tert-butyl-Nn- Propylamino group, N- (1-methylpropyl) -Nn-propylamino group,

  N-methyl-N-iso-propylamino group, N-ethyl-N-iso-propylamino group, N-iso-propyl-Nn-propylamino group, N, N-di (iso-propyl) amino group N-butyl-N-iso-propylamino group, N-iso-butyl-N-iso-propylamino group, N-tert-butyl-N-iso-propylamino group, N- (1-methylpropyl) ) -N-iso-propylamino group, Nn-butyl-N-methylamino group, Nn-butyl-N-ethylamino group, Nn-butyl-Nn-propylamino group, N- n-butyl-N-iso-propylamino group, N, N-di (n-butylamino) group, Nn-butyl-N-iso-butylamino group, Nn-butyl-N-tert-butyl Amino group, N- -Butyl-N- (1-methylpropyl) amino group, N-iso-butyl-N-methylamino group, N-iso-butyl-N-ethylamino group, N-iso-butyl-Nn-propylamino group Group, Nn-butyl-N-iso-propylamino group, N, N-di (iso-butylamino) group, N-iso-butyl-N-ter-butylamino group,

  N-iso-butyl-N-tert-butylamino group, N-iso-butyl-N-1-methylpropylamino group, N-ter-butyl-N-methylamino group, N-ter-butyl-N-ethyl Amino group, N-ter-butyl-Nn-propylamino group, N-ter-butyl-N-iso-propylamino group, N, N-di (ter-butylamino) group, N-ter-butyl- N-iso-butylamino group, Nn-butyl-N-tert-butylamino group, N-ter-butyl-N- (1-methylpropyl) amino group, N-methyl-N- (1-methylpropyl) ) Amino group, N-ethyl-N- (1-methylpropyl) amino group, N- (1-methylpropyl) -Nn-propylamino group, N- (1-methylpropyl) -N-iso-propyla Group, Nn-butyl 1-methylpropylamino group, N-iso-butyl-N- (1-methylpropyl) amino group, N-tert-butyl-N- (1-methylpropyl) amino group, N , N-di (1-methylpropyl) amino group, and the like.

Since the effects of the present invention is good, X ₁ to X ₃ is an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, preferably a hydroxyl group. Furthermore, since solubility is favorable, it is preferable that they are any of a methyl group, an ethyl group, a methoxy group, an ethoxy group, and a hydroxyl group.

In General formula (2), n, m, and p represent the integer of 0-3 each independently. These represent the number of substitutions of X _{1 to} X ₃ , and the substitution positions are arbitrary. n, m and p are preferably n + m + p <4 from the effect and solubility of the present invention, and most preferably n = m = p = 0.

In General formula (2), k and q represent the integer of 0-2 each independently. When q is 0, the cyclic alkyl part of the general formula (2) is a cyclopentyl part corresponding to X _{1 to} X ₃ , n, m and p, and when q is 1, it is a corresponding cyclohexyl part, Is a corresponding cycloheptyl moiety. In the general formula (2), k represents the number of methylene groups up to the cyclic alkyl part corresponding to X _{1 to} X ₃ , n, m and p and the carbonyl group.

In the α-amino acid derivative of the present invention, it is preferable that the general formula (2) has a cyclohexyl part (q = 1) because the effect is good. That is, a cyclohexanecarbonyl group corresponding to X _{1 to} X ₃ , n, m, and p, a corresponding cyclohexylacetyl group, and a corresponding 3-cyclohexylpropionyl group are preferable. Furthermore, since the solubility is good and the effect is good, cyclohexanecarbonyl group (n = m = p = k = 0, q = 1), cyclohexylacetyl group (n = m = p = 0, k = 1) Q = 1) or 3-cyclohexylpropionyl group (n = m = p = 0, k = 2, q = 1), and most preferred is a cyclohexanecarbonyl group (n = m = p). = K = 0, q = 1).

In the general formula (1), when one of R ₃ and R ₄ is a group represented by the general formula (2), as described above, one (the other) is a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, Any one of allyl groups is preferable because the effect is good. Furthermore, since the effect is favorable, it is preferably any of a hydrogen atom, a methyl group, and an ethyl group, and most preferably a hydrogen atom or a methyl group.

  Specific examples of preferable α-amino acid derivatives corresponding to these include N-cyclohexanecarbonylglycine, N-cyclohexanecarbonylsarcosine, N-cyclohexanecarbonyl-L-alanine, N-cyclohexanecarbonyl-DL-alanine, and N-cyclohexane. Carbonyl-D-alanine, (N-cyclohexanecarbonyl) methylalanine, N-cyclohexanecarbonyl-L-serine, N-cyclohexanecarbonyl-DL-serine, N-cyclohexanecarbonyl-D-serine, N-cyclohexylacetylglycine, N- Cyclohexylacetylsarcosine, N-cyclohexylacetyl-L-alanine, N-cyclohexylacetyl-DL-alanine, N-cyclohexylacetyl-D-alanine, (N-cyclo Hexyl acetyl) methyl alanine, N- cyclohexyl-acetyl -L- serine, N- cyclohexyl-acetyl -DL- serine, N- cyclohexyl-acetyl -D- serine.

  More preferably, N-cyclohexanecarbonylglycine, N-cyclohexanecarbonylsarcosine, N-cyclohexanecarbonyl-L-alanine, N-cyclohexanecarbonyl-DL-alanine, N-cyclohexanecarbonyl-D-alanine, (N-cyclohexanecarbonyl) Methylalanine, N-cyclohexanecarbonyl-L-serine, N-cyclohexanecarbonyl-DL-serine N-cyclohexanecarbonyl-D-serine.

In the general formula (3), X _{1 to} X ₃ , k, n, m, and p are the same as those in the general formula (2). When k is 0, the group represented by the general formula (3) is a benzoyl group corresponding to X _{1 to} X ₃ , n, m and p, and when k is 1, it is a phenylacetyl group corresponding to these. , K is 2, it becomes a phenylpropionyl group corresponding to these. X _{1 to} X ₃ are preferably any one of a hydroxyl group, a methyl group, an ethyl group, a propyl group, a methoxy group, an ethoxy group, and a propyloxy group because the effects and solubility of the present invention are good. Most preferred is a methoxy group. n, m and p are preferably n + m + p <4 because the effect of the present invention is good, and more preferably n + m + p <2 because the solubility is good. Therefore, n = m = p = 0 is most preferable. k is preferably 0 or 1 because the effect is good.

  Specific examples of the group represented by the general formula (3) include benzoyl group, p-anisoyl (4-methoxybenzoyl) group, m-anisoyl (3-methoxybenzoyl) group, o-anisoyl (2- Methoxybenzoyl) group, 4-ethoxybenzoyl group, 3-ethoxybenzoyl group, 2-ethoxybenzoyl group, 4-propoxybenzoyl group, 3-propoxybenzoyl group, 2-propoxybenzoyl group, 2,4-dimethoxybenzoyl group, 3 , 4-dimethoxybenzoyl group, 3,4,5-trimethoxybenzoyl group, 2,3,4-trimethoxybenzoyl group, 2-hydroxybenzoyl (salicyl) group, 3-hydroxybenzoyl group, 4-hydroxybenzoyl group, 2,4-dihydroxybenzoyl group, 3,4-dihydroxybenzoyl 3,4,5-trihydroxybenzoyl (galloyl) group, 2-hydroxy-4-methoxybenzoyl group, 3-hydroxy-4-methoxybenzoyl group, 4-hydroxy-3-methoxybenzoyl group, 2-methylbenzoyl ( o-toluyl) group, 3-methylbenzoyl (m-toluyl) group, 4-methylbenzoyl (p-toluyl) group, 2-ethylbenzoyl group, 3-ethylbenzoyl group, 4-ethylbenzoyl group, 2-propylbenzoyl Group, 3-propylbenzoyl group, 4-propylbenzoyl group,

  Phenylacetyl group, 4-methoxyphenylacetyl group, 3-methoxyphenylacetyl group, 2-methoxyphenylacetyl group, 4-ethoxyphenylacetyl group, 3-ethoxyphenylacetyl group, 2-ethoxyphenylacetyl group, 4-propoxyphenyl Acetyl group, 3-propoxyphenylacetyl group, 2-propoxyphenylacetyl group, 2,4-dimethoxyphenylacetyl group, 3,4-dimethoxyphenylacetyl group, 3,4,5-trimethoxyphenylacetyl group, 2-hydroxy Phenylacetyl group, 3-hydroxyphenylacetyl group, 4-hydroxyphenylacetyl group, N-2,4-dihydroxyphenylacetyl group, N-3,4-dihydroxyphenylacetyl group, N-3,4,5-trihydroxy Phenylacetate Group, 2-hydroxy-4-methoxyphenylacetyl group, 3-hydroxy-4-methoxyphenylacetyl group, 4-hydroxy-3-methoxyphenylacetyl group, 2-methylphenylacetyl group, 3-methylphenylacetyl group, 4-methylphenylacetyl group, 2-ethylphenylacetyl group, 3-ethylphenylacetyl group, 4-ethylphenylacetyl group, 2-propylphenylacetyl group, 3-propylphenylacetyl group, 4-propylphenylacetyl group,

  Phenylpropionyl group, 4-methoxyphenylpropionyl group, 3-methoxyphenylpropionyl group, 2-methoxyphenylpropionyl group, 4-ethoxyphenylpropionyl group, 3-ethoxyphenylpropionyl group, 2-ethoxyphenylpropionyl group, 4-propoxyphenyl Propionyl group, 3-propoxyphenylpropionyl group, 2-propoxyphenylpropionyl group, 2,4-dimethoxyphenylpropionyl group, 3,4-dimethoxyphenylpropionyl group, 3,4,5-trimethoxyphenylpropionyl group, 2-hydroxy Phenylpropionyl group, 3-hydroxyphenylpropionyl group, 4-hydroxyphenylpropionyl group, N-2,4-dihydroxyphenylpropionyl group, N-3,4-dihydride Xiphenylpropionyl group, N-3,4,5-trihydroxyphenylpropionyl group, 2-hydroxy-4-methoxyphenylpropionyl group, 3-hydroxy-4-methoxyphenylpropionyl group, 4-hydroxy-3-methoxyphenylpropionyl group Group, 2-methylphenylpropionyl group, 3-methylphenylpropionyl group, 4-methylphenylpropionyl group, 2-ethylphenylpropionyl group, 3-ethylphenylpropionyl group, 4-ethylphenylpropionyl group, 2-propylphenylpropionyl group , 3-propylphenylpropionyl group, 4-propylphenylpropionyl group and the like.

  More preferred groups represented by the general formula (3) are a benzoyl group, a p-anisoyl (4-methoxybenzoyl) group, an m-anisoyl (3-methoxybenzoyl) group, an o-anisoyl (2-methoxybenzoyl) group, A phenylacetyl group, a 4-methoxyphenylacetyl group, a 3-methoxyphenylacetyl group, and a 2-methoxyphenylacetyl group; Most preferred is a benzoyl group or a phenylacetyl group.

When one of R ₃ and R ₄ in the general formula (1) is a group represented by the general formula (3), as described above, when both R ₁ and R ₂ are hydrogen atoms (glycine derivatives) , One of R ₃ and R ₄ is an alkyl group or an allyl group having 1 to 3 carbon atoms, and is not a hydrogen atom. Any value within this range may be used, but a methyl group is preferable since the effect is good. In addition, when one or both of R ₁ and R ₂ are CH ₃ groups (alanine derivatives and methylalanine derivatives), or R ₁ is a hydrogen atom and R ₂ is a CH ₂ OH group (serine derivative), R ₃ And one of R ₄ is a group represented by the general formula (3), one (the other) may be any as long as it is a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or an allyl group. Since the effect of this invention is favorable, it is preferable that they are a hydrogen atom or a methyl group. Most preferred is a hydrogen atom.

  Preferred equivalent α-amino acid derivatives include N-benzoylsarcosine, N-phenylacetylsarcosine, N-benzoyl-L-alanine, N-benzoyl-DL-alanine, N-benzoyl-D-alanine, (N- Benzoyl) methylalanine, N-benzoyl-L-serine, N-benzoyl-DL-serine, N-benzoyl-D-serine, N-phenylacetyl-L-alanine, N-phenylacetyl-DL-alanine, N-phenyl Examples include acetyl-D-alanine, (N-phenylacetyl) methylalanine, N-phenylacetyl-L-serine, N-phenylacetylserine, and N-phenylacetylserine.

  In the present invention, any of the α-amino acid derivatives represented by the general formula (1) may be a salt, and any combination of salts may be used. Examples of the salt combinations include alkali metal ions such as sodium, potassium, calcium, zinc and magnesium, and alkaline earth metal ions, ammonium ions, amine ions such as methylamine, pyridine, trimethylamine and triethanolamine, hydrochloric acid, sulfuric acid and phosphorus Acids, hydrobromic acid, alkyl sulfuric acid such as methyl sulfuric acid and p-toluenesulfonic acid, acetic acid, lactic acid, maleic acid, fumaric acid, oxalic acid, succinic acid, tartaric acid, citric acid and other acids, betaine, glycine, serine, Examples include amino acids such as taurine, but the present invention is not limited thereto.

  In the present invention, the α-amino acid derivative is (N-methyl) methylalanine, N-carbobenzyloxyglycine, N-carbobenzyloxysarcosine, (N-carbobenzyloxy) methylalanine, N-acetyl-L-alanine. N-acetyl-DL-alanine, N-acetyl-D-alanine, N-acetyl-L-serine, N-acetyl-DL-serine, N-acetyl-D-serine, N-acetylsarcosine, (N-acetyl) ) Methylalanine, N-cyclohexanecarbonylglycine, N-cyclohexanecarbonylsarcosine, N-cyclohexanecarbonyl-L-alanine, N-cyclohexanecarbonyl-DL-alanine, N-cyclohexanecarbonyl-D-alanine, (N-cyclohexanecarbonyl) methyl Alanine, -Cyclohexanecarbonyl-L-serine, N-cyclohexanecarbonyl-DL-serine, N-cyclohexanecarbonyl-D-serine, N-benzoyl-L-serine, N-benzoyl-DL-serine, N-benzoyl-L-serine, N-benzoyl-L-alanine, N-benzoyl-DL-alanine, N-benzoyl-D-alanine, (N-benzoyl) methylalanine, N-benzoylsarcosine, N-phenylacetyl-L-serine, N-phenylacetyl -DL-serine, N-phenylacetyl-D-serine, N-phenylacetyl-L-alanine, N-phenylacetyl-DL-alanine, N-phenylacetyl-D-alanine, (N-phenylacetyl) methylalanine, N-phenylacetylsarcosine and their salts In the case of a compound selected from the group consisting of the above, it has the best effects of inhibiting keratinization, shrinking pores, preventing and improving rough skin, good solubility in preparations, and safety issues such as sensory stimulation. It is excellent in that it has high safety and solves the object of the present invention.

  It is novel that the α-amino acid derivative represented by the general formula (1) and the salt thereof according to the present invention have an effect of inhibiting keratinization, reducing pores, and preventing and improving rough skin.

  When the α-amino acid derivative represented by the general formula (1) according to the present invention has any of an alkyl group having 1 to 3 carbon atoms, an allyl group, and a carbobenzyloxy group, any of the corresponding α-amino acids or corresponding It can be easily obtained by introduction of an N-alkyl group, an N-allyl group, an N-carbobenzyloxy group, etc., corresponding to the analogs respectively.

  In addition, when the α-amino acid derivative represented by the general formula (1) according to the present invention has a group represented by the general formula (2), the general formula (2) corresponding to the corresponding α-amino acid or analog, respectively. It can be easily obtained by introduction of a group represented by In addition, the deprotection after introduction of the protected group represented by the general formula (2), and the introduction to the general formula (2) after introduction of the group corresponding to the general formula (2) It is possible to get to.

  Moreover, when the α-amino acid derivative represented by the general formula (1) according to the present invention has a group represented by the general formula (3), any of the general formulas corresponding to the corresponding α-amino acid or analog ( It can be easily obtained by introduction of the group represented by 3). Further, deprotection after the introduction of the protected group represented by the general formula (3), and the introduction of the group represented by the general formula (3) to the alkyl on the aromatic ring by Friedel Crafts etc. It can be obtained by an easy method such as introduction of a group or selective alkylation of a phenolic hydroxyl group to lead to a group represented by the general formula (3).

  Although the typical synthesis example of the alpha-amino acid derivative based on this invention is given to the following, this invention is not limited to these.

(Synthesis example)

(1) N-benzoyl-DL-alanine 6.4 g of DL-alanine and 4.5 g of sodium hydroxide were dissolved in 100 mL of purified water, and 7.9 g of benzoyl chloride was added dropwise under ice cooling. After stirring for 6 hours, hydrochloric acid was added to adjust the pH to 2 or lower. The precipitated crude product was collected by filtration and recrystallized with ethanol water to obtain 8.7 g of the desired product.

(2) N-benzoyl-sarcosine By synthesizing DL-alanine in Synthesis Example (1) in place of sarcosine, the target product was obtained.

(3) N-benzoyl-DL-serine The target product was obtained by synthesizing DL-alanine in Synthesis Example (1) instead of DL-serine.

(4) (N-benzoyl) methylalanine The target product was obtained by synthesizing DL-alanine in Synthesis Example (1) instead of methylalanine.

(5) N-phenylacetyl-DL-alanine The target product was obtained by synthesizing benzoyl chloride of Synthesis Example (1) in place of phenylacetyl chloride.

(6) N-phenylacetyl-DL-serine The target product was obtained by synthesizing DL-alanine in Synthesis Example (5) instead of DL-serine.

(7) N-Phenylacetylsarcosine The target product was obtained by synthesizing DL-alanine in Synthesis Example (5) instead of sarcosine.

(8) (N-Phenylacetyl) methylalanine The target product was obtained by synthesizing DL-alanine in Synthesis Example (5) instead of methylalanine.

(9) N-cyclohexanecarbonyl-L-alanine 10 g of L-alanine and 9 g of sodium hydroxide were dissolved in 100 mL of purified water, and 14.9 g of cyclohexanecarbonyl chloride was added dropwise under ice cooling. After stirring for 5 hours, hydrochloric acid was added to adjust the pH to 2 or lower. After extraction with 500 mL of ethyl acetate, drying over magnesium sulfate and filtration, the filtrate was concentrated under reduced pressure, and the resulting residue was recrystallized from ethanol water to obtain 17.2 g of the desired product.

(10) N-cyclohexanecarbonyl sarcosine The target product was obtained by synthesizing L-alanine in Synthesis Example (9) instead of sarcosine.

(11) N-cyclohexanecarbonyl-DL-serine The target product was obtained by synthesizing L-alanine in Synthesis Example (9) in place of DL-serine.

(12) (N-Cyclohexanecarbonyl) methylalanine By synthesizing L-alanine in Synthesis Example (9) instead of methylalanine, the desired product was obtained.

(13) N-acetyl-L-alanine The target product was obtained by synthesizing cyclohexanecarbonyl chloride of Synthesis Example (9) in place of acetyl chloride.

(14) N-acetyl-L-serine The target product was obtained by synthesizing L-alanine in Synthesis Example (13) instead of L-serine.

(15) N-acetylsarcosine The target product was obtained by synthesizing L-alanine in Synthesis Example (13) instead of sarcosine.

(16) (N-acetyl) methylalanine The target product was obtained by synthesizing L-alanine in Synthesis Example (13) in place of methylalanine.

  As will be proved later, the α-amino acid derivative represented by the general formula (1) and the salt thereof according to the present invention have an excellent function of suppressing keratinization, a function of reducing pores, and preventing and improving rough skin. It has the function to do. Accordingly, one or more compounds selected from the group consisting of the α-amino acid derivative represented by the general formula (1) and a salt thereof according to the present invention are a keratinization inhibitor, a pore reducing agent, and a rough skin prevention. -Useful as an improving agent.

  The α-amino acid derivative represented by the general formula (1) and a salt thereof are contained as active ingredients, and are useful as a keratinization inhibitor, a pore reducing agent, and a rough skin prevention / improving agent. This keratinization inhibitor, pore-reducing agent, and rough skin prevention / improving agent are preferably applied in a form that is applied externally to the skin, for example, improving the conspicuousness of pores on the nose, cheeks, etc. for the face, and preventing rough skin・ Improves and improves the conspicuousness of pores after body hair removal treatment for body, etc. to prevent and improve rough skin.

  The keratinization inhibitor, pore-reducing agent, and rough skin prevention / improving agent are novel and useful based on the discovery of the novel function of the α-amino acid derivative represented by the general formula (1) and a salt thereof according to the present invention. Application.

  Since the above-mentioned keratinization inhibitor, pore reducing agent and rough skin prevention / improving agent according to the present invention are highly safe, they have a very wide application range and can be applied to various fields. Examples of the field include cosmetics including quasi-drugs, pharmaceuticals, and foods, which are suitable.

  In addition, the α-amino acid derivative represented by the general formula (1) and the salt thereof, which is a keratinization inhibitor, a pore reducing agent, or a rough skin preventing / improving agent according to the present invention, have no sensory irritation. It is blended in the composition for external use, and is prepared as a composition for external use on the skin having functions such as a function for suppressing keratinization, a function for reducing pores, and a function for preventing and improving rough skin.

  The α-amino acid derivative represented by the general formula (1) and a salt thereof include a pore-reducing agent, a facial cosmetic that improves the conspicuousness of pores such as the nose and cheeks, and prevents and improves rough skin, especially for the face. It can be suitably used for a skin external preparation for body and the like for improving the conspicuousness of pores after hair removal treatment of cosmetics, feet and the like.

  When the α-amino acid derivative represented by the general formula (1) and a salt thereof according to the present invention are contained in a composition such as a keratinization inhibitor, a pore-reducing agent, a rough skin prevention / improving agent, and a composition for external use on the skin. The α-amino acid derivative represented by the general formula (1) and a salt thereof are contained in an amount effective for exerting the function, and the content thereof is 0.001 to 20% in the total amount of the composition. 0 mass% is preferable, More preferably, it is 0.01-10.0 mass%, Most preferably, it is 0.2-5.0 mass%. In addition, when the α-amino acid derivative represented by the general formula (1) and a salt thereof are mixed and used, the upper limit of their total content is preferably 20.0% by mass or less, more preferably It is 10.0 mass% or less, and 5.0 mass% or less is particularly preferable.

  The composition for external use containing the keratinization inhibitor, pore reducing agent, rough skin prevention / improving agent according to the present invention is a component usually used for external preparations for skin such as cosmetics and pharmaceuticals, such as oil, surfactant, powder. , Coloring materials, water, alcohols, thickeners, chelating agents, silicones, antioxidants (antioxidants), UV absorbers, moisturizers, fragrances, various medicinal ingredients, preservatives, neutralizing agents, pH adjustment It can mix | blend suitably as needed, such as an agent.

  Of the above optional ingredients, specific examples of the oil include, for example, avocado oil, camellia oil, turtle oil, macadamia nut oil, corn oil, mink oil, olive oil, rapeseed oil, egg yolk oil, sesame oil, persic oil, wheat Germ oil, sasanqua oil, castor oil, flaxseed oil, safflower oil, cottonseed oil, evening primrose oil, eno oil, soybean oil, peanut oil, tea seed oil, kaya oil, rice bran oil, cinnagiri oil, Japanese kiri oil, jojoba oil, Liquid oils such as germ oil, triglycerin, glycerin trioctanoate, glycerin triisopalmitate, cocoa butter, coconut oil, horse fat, hydrogenated coconut oil, palm oil, beef tallow, sheep fat, hardened beef tallow, palm kernel oil, pork tallow , Solid oils such as molasses kernel oil, hydrogenated oil, molasses, hydrogenated castor oil, beeswax, candelilla wax, carnauba wax, lanolin, lanolin acetate, liquid lanoli Sugarcane wax, lanolin fatty acid isopropyl, hexyl laurate, reduced lanolin, jojoba wax, hard lanolin, polyoxyethylene (hereinafter referred to as POE) lanolin alcohol ether, POE lanolin alcohol acetate, lanolin fatty acid polyethylene glycol, POE hydrogenated lanolin alcohol ether Hydrocarbons such as waxes, liquid paraffin, ozokerite, squalene, paraffin, ceresin, squalane, petrolatum, microcrystalline wax, etc.

  Isopropyl myristate, cetyl octanoate, octyldodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, hexyl decyl dimethyloctanoate, cetyl lactate, myristyl lactate, lanolin acetate, stearic acid Isocetyl, isocetyl isostearate, cholesteryl 12-hydroxystearylate, ethylene glycol di-2-ethylhexylate, dipentaerythritol fatty acid ester, N-alkyl glycol monoisostearate, neopentyl glycol dicaprate, diisostearyl malate, di-2- Glyceryl heptyl undecanoate, trimethylolpropane tri-2-ethylhexylate, trimethylolpropane triisostearate Pentaerythritol tetra-2-ethylhexylate, glyceryl tri-2-ethylhexylate, trimethylolpropane triisostearate, cetyl-2-ethylhexanoate, 2-ethylhexyl palmitate, glyceryl trimyristate, glyceride tri-2-heptylundecanoate, Castor oil fatty acid methyl ester, oleic oil, acetoglyceride, 2-heptylundecyl palmitate,

  Diisopropyl adipate, N-lauroyl-L-glutamic acid-2-octyldodecyl ester, di-2-heptylundecyl adipate, di-2-ethylhexyl sebacate, 2-hexyldecyl myristate, 2-hexyldecyl palmitate, Ester oils such as adipic acid-2-hexyldecyl, diisopropyl sebacate, succinic acid-2-ethylhexyl, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, 12-hydroxystearic acid, undecylenic acid, Lanolin fatty acid, isostearic acid, linoleic acid, linolenic acid, eicosapentaenoic acid and other higher fatty acids, lauryl alcohol, cetyl alcohol, stearyl alcohol, behenyl alcohol, myristyl alcohol, oleyl alcohol Linear, branched higher alcohols such as cetostearyl alcohol, monostearyl glycerin ether (batyl alcohol), 2-decyltetradecinol, lanolin alcohol, cholesterol, phytosterol, hexyldodecanol, isostearyl alcohol, octyldodecanol, dimethylpolysiloxane And silicone oils such as methylphenylpolysiloxane, perfluorocarbons such as perfluorohexane and triperfluoro-n-butylamine, and perfluoropolyethers.

  Examples of the surfactant include soap bases, fatty acid soaps such as sodium laurate and sodium palmitate, higher alkyl sulfates such as sodium lauryl sulfate and potassium lauryl sulfate, POE lauryl sulfate triethanolamine, and POE lauryl. Alkyl ether sulfate such as sodium sulfate, N-acyl sarcosine acid such as sodium lauroyl sarcosine, N-myristoyl-N-methyl taurate sodium, higher fatty acid amide sulfonic acid such as coconut oil fatty acid methyl tauride sodium, POE stearyl ether phosphorus Phosphate salts such as acids, sulfosuccinates such as sodium monolauroyl monoethanolamide POE sulfosuccinate, sodium lauryl polypropylene glycol sulfosuccinate, Sodium near dodecylbenzenesulfonate, alkyl benzene sulfonates such as linear dodecylbenzenesulfonate, triethanolamine,

  N-acyl glutamates such as disodium N-stearoyl glutamate, monosodium N-stearoyl glutamate, higher fatty acid ester sulfates such as hydrogenated coconut oil fatty acid sodium glycerol sulfate, sulfated oils such as funnel oil, POE alkyl ether carboxylic acid Anionic surfactants such as POE alkyl allyl ether carboxylate, higher fatty acid ester sulfonate, secondary alcohol sulfate, higher fatty acid alkylolamide sulfate, sodium lauroyl monoethanolamide succinate, sodium caseinate; Dialkyldimethylammonium salts such as stearyltrimethylammonium chloride, alkyltrimethylammonium salts such as lauryltrimethylammonium chloride, and distearyldimethylammonium chloride Umum salts, alkyl pyridinium salts such as cetyl pyridinium chloride, alkyl quaternary ammonium salts, alkyl dimethyl benzyl ammonium salts, alkyl isoquinolinium salts, dialkyl morphonium salts, POE alkyl amines, alkyl amine salts, polyamine fatty acid derivatives, amyl Cationic surfactants such as alcohol fatty acid derivatives and benzalkonium chloride;

  Amphoteric surfactants such as imidazoline-based amphoteric surfactants such as 2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt, and betaine-based surfactants such as amide betaine and sulfobetaine;

  Sorbitan fatty acid esters such as sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan trioleate, mono cottonseed oil fatty acid glycerin, glyceryl monostearate, glyceryl sesquioleate, glyceryl monostearate Lipophilic nonionic surface activity such as glycerin polyglycerin fatty acids such as malate, propylene glycol fatty acid esters such as propylene glycol monostearate, hardened castor oil derivative, glycerin alkyl ether, POE / methylpolysiloxane copolymer Agent;

  POE sorbitan monooleate, POE sorbitan fatty acid esters such as POE sorbitan monostearate, POE sorbite monolaurate, POE sorbite monooleate such as POE sorbit monooleate, POE glycerin monooleate, POE glycerol fatty acid esters such as POE glycerol distearate, POE monooleate, POE distearate, POE fatty acid esters such as POE monodiolate, POE alkyl ethers such as POE lauryl ether, POE oleyl ether, POE cholestanol ester, POE octylphenyl POE alkyl phenyl ethers such as ether and POE nonyl phenyl ether,

  POE / polyoxypropylene (hereinafter referred to as POP) monobutyl ether, POE / POP cetyl ether, POE / POP alkyl ethers such as POE / POP glycerin ether, POE castor oil, POE hydrogenated castor oil, POE hydrogenated castor oil monoiso Stearates, POE castor oil hardened castor oil derivatives such as POE hardened castor oil maleic acid, POE beeswax and lanolin derivatives such as POE sorbit beeswax, alkanolamides such as coconut oil fatty acid diethanolamide, fatty acid isopropanolamide, POE propylene glycol fatty acid ester, Examples thereof include hydrophilic nonionic surfactants such as POE fatty acid amide, POE alkylamine, sucrose fatty acid ester, and alkylethoxydimethylamine oxide.

  Examples of the powder include mica, talc, kaolin, sericite (sericite), muscovite, phlogopite, synthetic mica, saucite, biotite, lithia mica, synthetic mica, calcium carbonate, magnesium carbonate, anhydrous silica. Acid (silica), aluminum silicate, barium silicate, calcium silicate, magnesium silicate, strontium silicate, aluminum oxide, barium sulfate, bengara, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, bitumen, titanium oxide , Zinc oxide, mica titanium (titanium oxide coated mica), fish phosphorus foil, bismuth oxychloride, boron nitride, red 228, red 226, blue 404, polyethylene powder, polymethyl methacrylate powder, polyamide resin powder (nylon Powder), cellulose powder, organopolysiloxane elastomer, aluminum Umm powder, mention may be made of copper powder and the like.

  Examples of alcohols include lower alcohols such as methanol, ethanol, propanol, and isopropanol; cholesterol, sitosterol, lanosterol, and the like.

  Examples of thickeners include plant polymers such as gum arabic, tragacanth cam, galactan, carop gum, guar gum, carrageenan, pectin, agar, starch (corn, wheat, potato, rice), and microorganisms such as dextran and pullulan. Polymers, starch polymers such as carboxymethyl starch and methylhydroxypropyl starch, animal polymers such as collagen, casein, gelatin, methylcellulose, nitrocellulose, ethylcellulose, hydroxyethylcellulose, sodium cellulose sulfate, hydroxypropylcellulose, carboxy Cellulose polymers such as methyl cellulose and crystalline cellulose, alginic acid polymers such as sodium alginate and propylene glycol alginate, polyvinyl Vinyl polymers such as ethers and carboxyvinyl polymers, POE polymers, POE polyoxypropylene copolymer polymers, acrylic polymers such as sodium polyacrylate and polyacrylamide, polyethyleneimine, cationic polymers, bentonite And water-soluble polymers such as inorganic water-soluble polymers such as magnesium aluminum silicate, laponite, hectorite, and silicic anhydride.

  Examples of chelating agents include citramalic acid, agaric acid, glyceric acid, shikimic acid, hinokitiol, gallic acid, tannic acid, caffeic acid, ethylenediaminetetraacetic acid, ethyleneglycoldiaminetetraacetic acid, diethylenetriaminepentaacetic acid, phytic acid, polyphosphoric acid. Examples thereof include acids, metaphosphoric acids, analogs thereof, and alkali metal salts and carboxylic acid esters thereof.

  Examples of the ultraviolet absorber include benzoic acid ultraviolet absorbers such as paraaminobenzoic acid; anthranilic acid ultraviolet absorbers such as methyl anthranilate; salicylic acid ultraviolet absorbers such as octyl salicylate; isopropyl paramethoxycinnamate. And cinnamic acid UV absorbers such as octyl paramethoxycinnamate; and UV absorbers such as urocanic acid and ethyl urocanate.

  Examples of the humectant include polyethylene glycol (hereinafter referred to as PEG), propylene glycol, dipropylene glycol, 1,3-butylene glycol, glycerin, diglycerin, xylitol, maltitol, maltose, D-mannitol, Examples thereof include glucose, fructose, sodium chondroitin sulfate, sodium hyaluronate, sodium lactate, glucosamine, and cyclodextrin.

  Examples of medicinal ingredients include vitamin A oil, retinol, retinol palmitate, pyridoxine hydrochloride, benzyl nicotinate, nicotinamide, nicotinic acid dl-α-tocopherol, ascorbic acid magnesium phosphate, vitamin D2, dl-α -Vitamins such as tocopherol, pantothenic acid and biotin; anti-inflammatory agents such as azulene and glycyrrhizin; whitening agents such as arbutin; hormones such as estradiol; astringents such as zinc oxide and tannic acid; L-menthol and camphor Coolant; Other lysozyme chloride, pyridoxine hydrochloride, sulfur and the like can be blended. Furthermore, various extracts showing various medicinal effects can be blended. That is, there can be mentioned, for example, dokudami extract, apricot extract, licorice extract, peony extract, button pi extract, loofah extract, cypress extract, eucalyptus extract, clove extract, maronier extract, cornflower extract, seaweed extract, thyme extract and the like.

  Examples of preservatives include benzoic acid, salicylic acid, paraoxybenzoic acid esters (methyl paraben, ethyl paraben, butyl paraben, etc.), sorbic acid, parachlorometacresol, hexachlorophene, benzalkonium chloride, chlorhexidine chloride, trichlorocarba Nilide, photosensitizer, phenoxyethanol and the like can be mentioned.

  Other neutralizing agents such as 2-amino-2-methyl-1-propanol, 2-amino-2-methyl-1,3-propanediol, potassium hydroxide, potassium hydroxide, triethanolamine, sodium carbonate, etc. PH adjusters such as lactic acid, citric acid, glycolic acid, succinic acid, tartaric acid, malic acid, sodium hydrogen carbonate ammonium hydrogen carbonate; antioxidants such as ascorbic acid, α-tocopherol, carotenoids, etc. are incorporated into the preparation of the present invention. be able to.

  The said component is an illustration and is not limited to these. Further, these components can be appropriately combined and blended in accordance with a prescription according to a desired form.

  Compositions of the present invention, such as keratinization inhibitor, pore-reducing agent, rough skin prevention / improving agent, and composition for external application to skin, include pharmaceuticals, quasi-drugs (ointments, dentifrices, etc.) and cosmetics [face wash, milky lotion. , Creams, gels, essences (beauty liquids), packs, masks and other basic cosmetics; foundations, makeup products such as lipsticks, oral cosmetics, aromatic cosmetics, hair cosmetics, body cosmetics, etc.]. Note that these forms are not limited to the forms that the composition of the present invention, such as the keratinization inhibitor, pore reducing agent, rough skin prevention / improving agent, and external composition for skin, can take.

  The dosage form includes a wide range of dosage forms such as aqueous solution, solubilization system, emulsification system, oil liquid system, gel system, ointment system, aerosol system, water-oil two-layer system, water-oil-powder three-layer system, etc. Can take.

  By using the keratinization inhibitor, pore reducing agent, and rough skin prevention / improving agent of the present invention, the keratinization is suppressed, the skin condition is maintained in a good state, and further improved, and the pores are further reduced. Thus, it is possible to provide a youthful and fresh skin with reduced pores.

  Hereinafter, the present invention will be specifically described with reference to examples. The blending amount is mass% unless otherwise specified.

“Example 1” Test for inhibiting keratinization The sample for evaluating α-amino acid derivatives and salts thereof was mainly prepared by 3 mass% aqueous solution (including 30 mass% ethanol). In addition, it adjusted with hydrochloric acid or sodium hydroxide so that pH might be set to 7.0-7.5. Moreover, when the solubility of the sample was low, a solution was prepared accordingly.

  100 μl of 10% by mass oleic acid (solvent: ethanol) was applied to the back of a hairless mouse (HR-1; Hoshino experimental animal). Thereafter, 100 μl of a sample solution (α-amino acid derivative or the like) was applied. This was continued for 3 days. The next day, the skin condition of the back was observed with a CCD camera, and rough skin conditions (stratum exfoliation and erythema) were evaluated. The skin condition of the control (control aqueous solution) application was set to 2.0, the condition without any rough skin was set to 0.0, and the visual evaluation was made at intervals of 0.25 points according to the skin condition. At the same time, the horny layer on the back of the hairless mouse is peeled off with tape, the nucleus is stained with hematoxylin, the degree of keratinization is observed, and the keratin angle in the range of 1.0 to 3.0 (in increments of 0.25). The chemical value was evaluated. In addition, it shows that there are many nucleated stratum corneum cells, ie, the keratinization progresses, so that a value is large. The results are shown in Table 1.

  As is apparent from Table 1, (N-methyl) methylalanine, N-carbobenzyloxyglycine, N-carbobenzyloxysarcosine, (N-carbobenzyloxy) methylalanine, N-acetyl-L-alanine, N- Acetyl-DL-alanine, N-acetyl-D-alanine, N-acetyl-L-serine, N-acetyl-DL-serine, N-acetyl-D-serine, N-acetylsarcosine, (N-acetyl) methylalanine N-cyclohexanecarbonylglycine, N-cyclohexanecarbonylsarcosine, N-cyclohexanecarbonyl-L-alanine, N-cyclohexanecarbonyl-DL-alanine, N-cyclohexanecarbonyl-D-alanine, (N-cyclohexanecarbonyl) methylalanine, N -Cyclohexa Carbonyl-L-serine, N-cyclohexanecarbonyl-DL-serine, N-cyclohexanecarbonyl-D-serine, N-benzoyl-L-serine, N-benzoyl-DL-serine, N-benzoyl-L-serine, N- Benzoyl-L-alanine, N-benzoyl-DL-alanine, N-benzoyl-D-alanine, (N-benzoyl) methylalanine, N-benzoylsarcosine, N-phenylacetyl-L-serine, N-phenylacetyl-DL -Serine, N-phenylacetyl-D-serine, N-phenylacetyl-L-alanine, N-phenylacetyl-DL-alanine, N-phenylacetyl-D-alanine, (N-phenylacetyl) methylalanine, N- Rough skin due to stratum corneum peeling and erythema on phenylacetylsarcosine Keep effect was observed. Moreover, the keratinization value was reduced. As mentioned above, the inhibitory effect of the keratinization was recognized by the said compound. On the other hand, N-acetylglycine, phosphonomethylglycine, and hippuric acid outside the scope of the present invention were not effective.

[Example 2] Human pore reduction effect An experiment in which a sample was applied twice a day for one month using a cheek part of a healthy male was carried out by five people in each group. A 3% by mass aqueous solution (including 15% by mass ethanol) of an α-amino acid derivative and a salt thereof was mainly prepared. In addition, it adjusted with hydrochloric acid or sodium hydroxide so that pH might be set to 7.0-7.5. When the solubility was low, a solution was prepared accordingly. As a control, a 15% by mass ethanol aqueous solution was used, and the sample aqueous solution and the control aqueous solution were applied on each side.

  Replicas were collected before and after continuous application, and changes in the shape of pores at the same site were observed with a three-dimensional laser scanning microscope. The size of the pores is evaluated by visual evaluation in 13 levels 1 to 13 (the larger the number, the larger the pores), and the difference between the scores before and after application (after application-before application) is calculated. The effectiveness of each sample was examined as a replica judgment value. The results are shown in Table 2.

  As is apparent from Table 2, (N-methyl) methylalanine, N-carbobenzyloxyglycine, N-carbobenzyloxysarcosine, (N-carbobenzyloxy) methylalanine, N-acetyl-L-alanine, N- Acetyl-DL-alanine, N-acetyl-D-alanine, N-acetyl-L-serine, N-acetyl-DL-serine, N-acetyl-D-serine, N-acetylsarcosine, (N-acetyl) methylalanine N-cyclohexanecarbonylglycine, N-cyclohexanecarbonylsarcosine, N-cyclohexanecarbonyl-L-alanine, N-cyclohexanecarbonyl-DL-alanine, N-cyclohexanecarbonyl-D-alanine, (N-cyclohexanecarbonyl) methylalanine, N -Cyclohexa Carbonyl-L-serine, N-cyclohexanecarbonyl-DL-serine, N-cyclohexanecarbonyl-D-serine, N-benzoyl-L-serine, N-benzoyl-DL-serine, N-benzoyl-L-serine, N- Benzoyl-L-alanine, N-benzoyl-DL-alanine, N-benzoyl-D-alanine, (N-benzoyl) methylalanine, N-benzoylsarcosine, N-phenylacetyl-L-serine, N-phenylacetyl-DL -Serine, N-phenylacetyl-D-serine, N-phenylacetyl-L-alanine, N-phenylacetyl-DL-alanine, N-phenylacetyl-D-alanine, (N-phenylacetyl) methylalanine, N- The effect of reducing pores was observed in phenylacetylsarcosine.

"Example 3" The inhibitory effect with respect to rough skin by oleic acid application.
In order to investigate the inhibitory effect of α-amino acid derivatives and their salts on rough skin caused by oleic acid application, the amount of water transpiration (TEWL value) before and after application was measured, and the difference was compared with the control (control aqueous solution). And examined the effect. The sample preparation and application method followed Example 1. TEWL was measured using a TEWA meter TM210 (Courage + Khazaka).

  100 μl of 10% by mass oleic acid (solvent: ethanol) was applied to the back of hairless mice (HR-1, 4 mice in each group). Thereafter, 100 μl of a sample solution (α-amino acid derivative or the like) was applied. This was continued for 3 days. The next day, the TEWL value of the back was measured and the values of 4 animals were averaged. The results are shown in Table 3. The larger the ΔTEWL value, the worse the rough skin.

  As is clear from Table 3, (N-methyl) methylalanine, N-carbobenzyloxyglycine, N-carbobenzyloxysarcosine, (N-carbobenzyloxy) methylalanine, N-acetyl-L-alanine, N- Acetyl-DL-alanine, N-acetyl-D-alanine, N-acetyl-L-serine, N-acetyl-DL-serine, N-acetyl-D-serine, N-acetylsarcosine, (N-acetyl) methylalanine N-cyclohexanecarbonylglycine, N-cyclohexanecarbonylsarcosine, N-cyclohexanecarbonyl-L-alanine, N-cyclohexanecarbonyl-DL-alanine, N-cyclohexanecarbonyl-D-alanine, (N-cyclohexanecarbonyl) methylalanine, N -Cyclohexa Carbonyl-L-serine, N-cyclohexanecarbonyl-DL-serine, N-cyclohexanecarbonyl-D-serine, N-benzoyl-L-serine, N-benzoyl-DL-serine, N-benzoyl-L-serine, N- Benzoyl-L-alanine, N-benzoyl-DL-alanine, N-benzoyl-D-alanine, (N-benzoyl) methylalanine, N-benzoylsarcosine, N-phenylacetyl-L-serine, N-phenylacetyl-DL -Serine, N-phenylacetyl-D-serine, N-phenylacetyl-L-alanine, N-phenylacetyl-DL-alanine, N-phenylacetyl-D-alanine, (N-phenylacetyl) methylalanine, N- By applying phenylacetyl sarcosine, ΔTEWL value Was significantly lower than the control aqueous solution, and an effect of preventing and improving rough skin was observed. On the other hand, N-acetylglycine, phosphonomethylglycine, and hippuric acid other than the scope of the present invention were not effective.

"Example 4" Sensory stimulation test.
20 female panels were each applied 1 mL each of the control aqueous solution and the sample aqueous solution prepared in Example 1 to each of the left and right cheeks with a cotton swab. Was evaluated, and the final evaluation was reported. Evaluation of irritation was evaluated based on the following four-point evaluation criteria, and the average of the evaluation scores was calculated and classified into the following criteria.

(Evaluation criteria)
3: Extremely strong irritation such as tingling, burning, tingling, and kayumi, cannot be continued.
2: Strong irritation such as tingling, burning, tingling, kayumi, and unacceptable.
1: Slight tingling, burning, tingling, sensation of sensation, etc., but slightly acceptable.
0: No particular irritation is felt.

(Evaluation criteria)
A: Evaluation point average less than 0.2 B: Evaluation point average 0.2 to less than 1.0 C: Evaluation point average 1.0 to less than 2.0 D: Evaluation point average 2.0 or more

  The results are shown in Table 4.

  As is clear from Table 4, (N-methyl) methylalanine, N-carbobenzyloxyglycine, N-carbobenzyloxysarcosine, (N-carbobenzyloxy) methylalanine, N-acetyl-L-alanine, N- Acetyl-DL-alanine, N-acetyl-D-alanine, N-acetyl-L-serine, N-acetyl-DL-serine, N-acetyl-D-serine, N-acetylsarcosine, (N-acetyl) methylalanine N-cyclohexanecarbonylglycine, N-cyclohexanecarbonylsarcosine, N-cyclohexanecarbonyl-L-alanine, N-cyclohexanecarbonyl-DL-alanine, N-cyclohexanecarbonyl-D-alanine, (N-cyclohexanecarbonyl) methylalanine, N -Cyclohexa Carbonyl-L-serine, N-cyclohexanecarbonyl-DL-serine, N-cyclohexanecarbonyl-D-serine, N-benzoyl-L-serine, N-benzoyl-DL-serine, N-benzoyl-L-serine, N- Benzoyl-L-alanine, N-benzoyl-DL-alanine, N-benzoyl-D-alanine, (N-benzoyl) methylalanine, N-benzoylsarcosine, N-phenylacetyl-L-serine, N-phenylacetyl-DL -Serine, N-phenylacetyl-D-serine, N-phenylacetyl-L-alanine, N-phenylacetyl-DL-alanine, N-phenylacetyl-D-alanine, (N-phenylacetyl) methylalanine, N- Phenylacetylsarcosine has no sensory irritation problems and is safe High it was confirmed. On the other hand, β-alanine disclosed as a conventional effect substance has a strong sensory stimulation at 3%, and many female panels cannot continue the stimulation test.

  Hereinafter, an external composition for skin is shown as an example of the preparation according to the present invention. All the compositions had excellent effects such as suppression of keratinization, reduction of pores, prevention and improvement of rough skin, and the like.

Formulation Example 1 Skin lotion component Amount (% by mass)
(1) 1,3-butylene glycol 6.0
(2) Glycerin 4.0
(3) Oleyl alcohol 0.1
(4) POE (20) sorbitan monolaurate 0.5
(5) POE (15) lauryl alcohol ester 0.5
(6) Ethanol 10.0
(7) (N-methyl) methylalanine 3.0
(8) Purified water residue

(Manufacturing method)
(8) (1) and (2) were dissolved in purified water at room temperature to obtain an aqueous phase. (6) (3), (4) and (5) were dissolved in ethanol and mixed and solubilized in the previous aqueous phase. Then (7) (N-methyl) methylalanine was added. Thereafter, it was filtered and filled to obtain a lotion.

Formulation Examples 2-38 Lotion Toner lotion of Formulation Examples 2-38 was replaced with 3.0% by mass of (N-methyl) methylalanine in the ingredients of Formulation Example 1, and the components of the following blending amounts were blended. Prepared in the same manner as in Formulation Example 1. In addition, the compounding quantity of purified water was adjusted so that the total compounding quantity might be 100 mass% in any formulation example. N-carbobenzyloxyglycine 3.0 mass% (formulation example 2), N-carbobenzyloxysarcosine 3.0 mass% (formulation example 3), (N-carbobenzyloxy) methylalanine 3.0 mass% (formulation Example 4), N-acetyl-L-alanine 3.0 mass% (formulation example 5), N-acetyl-DL-alanine 3.0 mass% (formulation example 6), N-acetyl-D-alanine 3.0 % By mass (Formulation Example 7), 3.0% by mass of N-acetyl-L-serine (Formulation Example 8), 3.0% by mass of N-acetyl-DL-serine (Formulation Example 9), N-acetyl-D- Serine 3.0 mass% (Formulation Example 10), N-acetylsarcosine 3.0 mass% (Formulation Example 11), (N-acetyl) methylalanine 3.0 mass% (Formulation Example 12), N-cyclohexanecarbonylglycine 3.0% by mass (Formulation Example 13 N-cyclohexanecarbonylsarcosine 3.0 mass% (Formulation Example 14), N-cyclohexanecarbonyl-L-alanine 3.0 mass% (Formulation Example 15), N-cyclohexanecarbonyl-DL-alanine 3.0 mass% ( Formulation Example 16), N-cyclohexanecarbonyl-D-alanine 3.0 mass% (Formulation Example 17), (N-cyclohexanecarbonyl) methylalanine 3.0 mass% (Formulation Example 18), N-cyclohexanecarbonyl-L- Serine 3.0 mass% (Formulation Example 19), N-cyclohexanecarbonyl-DL-serine 3.0 mass% (Formulation Example 20), N-cyclohexanecarbonyl-D-serine 3.0 mass% (Formulation Example 21), N-benzoyl-L-serine 3.0 mass% (formulation example 22), N-benzoyl-DL-serine 3.0 mass% (formulation example 2) ), N-benzoyl-L-serine 3.0 mass% (formulation example 24), N-benzoyl-L-alanine 3.0 mass% (formulation example 25), N-benzoyl-DL-alanine 3.0 mass% (Formulation Example 26), N-benzoyl-D-alanine 3.0 mass% (Formulation Example 27), (N-benzoyl) methylalanine 3.0 mass% (Formulation Example 28), N-benzoylsarcosine 3.0 mass % (Formulation example 29), N-phenylacetyl-L-serine 3.0 mass% (formulation example 30), N-phenylacetyl-DL-serine 3.0 mass% (formulation example 31), N-phenylacetyl- D-serine 3.0 mass% (Formulation Example 32), N-phenylacetyl-L-alanine 3.0 mass% (Formulation Example 33), N-phenylacetyl-DL-alanine 3.0 mass% (Formulation Example 34) ), N-phenylacetyl Ru-D-alanine 3.0 mass% (Formulation Example 35), (N-phenylacetyl) methylalanine 3.0 mass% (Formulation Example 36), N-phenylacetylsarcosine 3.0 mass% (Formulation Example 37) N-benzoyl-L-serine 1.0% by mass and (N-cyclohexyl) methylalanine 1.0% by mass (Formulation Example 38).

Formulation Example 39 Lotion lotion amount (mass%)
(Alcohol phase)
(1) Ethanol 10.0
(2) Oleyl alcohol 0.1
(3) POE (20) sorbitan monolaurate 0.5
(4) POE (15) lauryl ether 0.5
(5) Preservative appropriate amount (6) Fragrance appropriate amount (aqueous phase)
(7) N-benzoyl-DL-serine 3.0
(8) 1,3-butylene glycol 6.0
(9) Glycerin 4.0
(10) Ion exchange water remaining

(Manufacturing method)
An aqueous phase and an alcohol phase were prepared and mixed.

Formulation Examples 40-76 Lotion Toner lotion of Formulation Examples 40-76 was replaced with 3.0% by mass of N-benzoyl-DL-serine in the ingredients of Formulation Example 39, and the components of the following blending amounts were blended. Prepared in the same manner as in Formulation Example 39. In addition, the compounding quantity of purified water was adjusted so that the total compounding quantity might be 100 mass% in any formulation example. (N-methyl) methylalanine 3.0 mass% (formulation example 40), N-carbobenzyloxyglycine 3.0 mass% (formulation example 41), N-carbobenzyloxysarcosine 3.0 mass% (formulation example 42) ), (N-carbobenzyloxy) methylalanine 3.0 mass% (Formulation Example 43), N-acetyl-L-alanine 3.0 mass% (Formulation Example 44), N-acetyl-DL-alanine 3.0 Mass% (Formulation Example 45), N-acetyl-D-alanine 3.0 mass% (Formulation Example 46), N-acetyl-L-serine 3.0 mass% (Formulation Example 47), N-acetyl-DL- Serine 3.0 mass% (Formulation Example 48), N-acetyl-D-serine 3.0 mass% (Formulation Example 49), N-acetylsarcosine 3.0 mass% (Formulation Example 50), (N-acetyl) Methylalanine 3.0% by mass (made Example 51), N-cyclohexanecarbonylglycine 3.0 mass% (formulation example 52), N-cyclohexanecarbonyl sarcosine 3.0 mass% (formulation example 53), N-cyclohexanecarbonyl-L-alanine 3.0 mass% ( Formulation Example 54), N-cyclohexanecarbonyl-DL-alanine 3.0 mass% (Formulation Example 55), N-cyclohexanecarbonyl-D-alanine 3.0 mass% (Formulation Example 56), (N-cyclohexanecarbonyl) methyl Alanine 3.0% by mass (Formulation Example 57), N-cyclohexanecarbonyl-L-serine 3.0% by mass (Formulation Example 58), N-cyclohexanecarbonyl-DL-serine 3.0% by mass (Formulation Example 59), N-cyclohexanecarbonyl-D-serine 3.0% by mass (Formulation Example 60), N-benzoyl-L-serine 3.0 % (Formulation example 61), N-benzoyl-L-serine 3.0% by mass (formulation example 62), N-benzoyl-L-alanine 3.0% by mass (formulation example 63), N-benzoyl-DL- Alanine 3.0 mass% (Formulation Example 64), N-benzoyl-D-alanine 3.0 mass% (Formulation Example 65), (N-benzoyl) methylalanine 1.0 mass% (Formulation Example 66), N- Benzoyl sarcosine 1.0 mass% (formulation example 67), N-phenylacetyl-L-serine 3.0 mass% (formulation example 68), N-phenylacetyl-DL-serine 3.0 mass% (formulation example 69) N-phenylacetyl-D-serine 3.0% by mass (Formulation Example 70), N-phenylacetyl-L-alanine 3.0% by mass (Formulation Example 71), N-phenylacetyl-DL-alanine 3.0 % By mass (Formulation Example 72), N -Phenylacetyl-D-alanine 3.0 mass% (Formulation Example 73), (N-phenylacetyl) methylalanine 3.0 mass% (Formulation Example 74), N-phenylacetylsarcosine 3.0 mass% (Formulation Example) 75), N-benzoyl-DL-serine 1.0% by mass and N-cyclohexanecarbonylsarcosine 1.0% by mass (Formulation Example 76).

Formulation Example 77 Cream Ingredient Amount (% by mass)
(1) Stearyl alcohol 6.0
(2) Stearic acid 2.0
(3) Hydrogenated lanolin 4.0
(4) Squalane 9.0
(5) Octyldodecanol 10.0
(6) 1,3-butylene glycol 6.0
(7) PEG 1500 4.0
(8) POE (25) cetyl alcohol ester 3.0
(9) Glycerin monostearate 2.0
(10) N-benzoyl-DL-alanine 3.0
(11) Glycylglycine 3.0
(12) Tocopherol 0.1
(13) Purified water residue

(Manufacturing method)
(13) (6) and (7) were added to purified water and heated to 70 ° C. After (1) to (5) were heated and dissolved, (8) to (9) and (12) were added and adjusted to 70 ° C. (10) and (11) were added here. This was added to the previous aqueous phase, the emulsified particles were homogenized with a homomixer, and deaerated, filtered, and cooled to obtain a grease.

Formulation Examples 78 to 114 Cream Formulations containing the following blending amounts of ingredients in place of the lotions of Formulation Examples 78 to 114 in place of 3.0% by mass of N-benzoyl-DL-alanine in the ingredients of Formulation Example 77 Prepared similarly to Example 77. In addition, the compounding quantity of purified water was adjusted so that the total compounding quantity might be 100 mass% in any formulation example. (N-methyl) methylalanine 3.0 mass% (Formulation Example 78), N-carbobenzyloxyglycine 3.0 mass% (Formulation Example 79), N-carbobenzyloxysarcosine 3.0 mass% (Formulation Example 80) ), (N-carbobenzyloxy) methylalanine 3.0 mass% (Formulation Example 81), N-acetyl-L-alanine 3.0 mass% (Formulation Example 82), N-acetyl-DL-alanine 3.0 Mass% (Formulation Example 83), N-acetyl-D-alanine 3.0 mass% (Formulation Example 84), N-acetyl-L-serine 3.0 mass% (Formulation Example 85), N-acetyl-DL- Serine 3.0 mass% (formulation example 86), N-acetyl-D-serine 3.0 mass% (formulation example 87), N-acetyl sarcosine 3.0 mass% (formulation example 88), (N-acetyl) Methylalanine 3.0% by mass (made Example 89), N-cyclohexanecarbonylglycine 3.0% by mass (formulation example 90), N-cyclohexanecarbonylsarcosine 3.0% by mass (formulation example 91), N-cyclohexanecarbonyl-L-alanine 3.0% by mass ( Formulation Example 92), N-cyclohexanecarbonyl-DL-alanine 3.0 mass% (Formulation Example 93), N-cyclohexanecarbonyl-D-alanine 3.0 mass% (Formulation Example 94), (N-cyclohexanecarbonyl) methyl Alanine 3.0 mass% (Formulation Example 95), N-cyclohexanecarbonyl-L-serine 3.0 mass% (Formulation Example 96), N-cyclohexanecarbonyl-DL-serine 3.0 mass% (Formulation Example 97), N-cyclohexanecarbonyl-D-serine 3.0 mass% (formulation example 98), N-benzoyl-L-serine 3.0 % (Formulation example 99), N-benzoyl-DL-serine 3.0 mass% (formulation example 100), N-benzoyl-L-serine 3.0 mass% (formulation example 101), N-benzoyl-L- Alanine 3.0 mass% (Formulation Example 102), N-benzoyl-D-alanine 3.0 mass% (Formulation Example 103), (N-benzoyl) methylalanine 1.0 mass% (Formulation Example 104), N- Benzoyl sarcosine 1.0 mass% (Formulation Example 105), N-phenylacetyl-L-serine 3.0 mass% (Formulation Example 106), N-phenylacetyl-DL-serine 3.0 mass% (Formulation Example 107) N-phenylacetyl-D-serine 3.0% by mass (Formulation Example 108), N-phenylacetyl-L-alanine 3.0% by mass (Formulation Example 109), N-phenylacetyl-DL-alanine 3.0 mass% (Formulation Example 110), N-phenylacetyl-D-alanine 3.0 mass% (Formulation Example 111), (N-phenylacetyl) methylalanine 3.0 mass% (Formulation Example 112), N-phenylacetylsarcosine 3 0.0% by mass (Formulation Example 113), N-benzoyl-DL-alanine 1.0% by mass and N-benzoylsarcosine 1.0% by mass (Formulation Example 114).

Formulation Example 115 Cream component blending amount (% by mass)
(1) Stearic acid 5.0
(2) Stearyl alcohol 4.0
(3) Isopropyl myristate 18.0
(4) Glycerol monostearate 3.0
(5) Propylene glycol 10.0
(6) N-phenylacetyl-L-serine 2.0
(7) ACES 2.0
(8) Potassium hydroxide 0.2
(9) Sodium bisulfite 0.01
(10) Preservative appropriate amount (11) perfume appropriate amount (12) ion-exchanged water remaining

(Manufacturing method)
Propylene glycol, N-phenylacetyl-L-serine and potassium hydroxide were added to ion-exchanged water and dissolved, and heated to 70 ° C. (aqueous phase). The other components were mixed, heated and melted and kept at 70 ° C. (oil phase). The oil phase was gradually added to the aqueous phase to pre-emulsify it, and the mixture was uniformly emulsified with a homomixer, and then cooled to 30 ° C. while stirring well.

Formulation Example 116 Cosmetic liquid ingredient content (mass%)
(Phase A)
(1) Ethyl alcohol (95%) 10.0
(2) POE (20) Octyldodecanol 1.0
(3) Pantothenyl ethyl ether 0.1
(4) ASDA 4Na 1.5
(5) Methylparaben 0.15
(6) Ethanol 10.0
(Phase B)
(7) Potassium hydroxide 0.1
(Phase C)
(8) Glycerin 5.0
(9) Dipropylene glycol 10.0
(10) N-benzoyl-DL-alanine 2.0
(11) Carboxyvinyl polymer 0.2
(12) Purified water residue

(Manufacturing method)
The A phase and the C phase were uniformly dissolved, and the A phase was added to the C phase and solubilized. Then phase B was added and mixed.

Formulation Example 117 Emulsion component content (% by mass)
(1) Stearic acid 2.5
(2) Cetyl alcohol 1.5
(3) Vaseline 5.0
(4) Liquid paraffin 10.0
(5) POE (10) monooleate 2.0
(6) PEG 1500 3.0
(7) Triethanolamine 1.0
(8) Cyclohexanecarbonyl-L-serine 0.5
(9) Sodium bisulfite 0.01
(10) Ethylparaben 0.3
(11) Carboxyvinyl polymer 0.05
(12) Appropriate amount of fragrance (13) Ion exchange water

(Manufacturing method)
Carboxyvinyl polymer was dissolved in a small amount of ion-exchanged water (A phase). PEG 1500, cyclohexanecarbonyl-L-serine, and triethanolamine were added to the remainder of the ion exchange water, dissolved by heating and kept at 70 ° C. (aqueous phase). The other components were mixed, heated and melted and kept at 70 ° C. (oil phase). The oil phase was added to the aqueous phase for pre-emulsification, and the A phase was added and uniformly emulsified with a homomixer, and then cooled to 30 ° C. while stirring well.

Formulation Example 118 Gel component amount (% by mass)
(1) 95% ethanol 10.0
(2) Dipropylene glycol 15.0
(3) POE (15) oleyl alcohol ale 2.0
(4) N-carbobenzyloxysarcosine 1.0
(5) Sodium bisulfite 0.03
(6) Carboxyvinyl polymer (“Carbopol 941”) 1.0
(7) Caustic potash 0.15
(8) L-arginine 0.1
(9) Perfume appropriate amount (10) Preservative appropriate amount (11) Purified water remainder

(Manufacturing method)
(11) (4) and (6) were uniformly dissolved in purified water (aqueous phase). On the other hand, (2), (3), and (5), (9), (10) were dissolved in (1) and added to the aqueous phase. Next, the gel was neutralized and thickened with (7) and (8) to obtain a gel.

Formulation Example 119 Pack component Compounding amount (% by mass)
(Phase A)
Dipropylene glycol 5.0
POE (60) hydrogenated castor oil 5.0
(Phase B)
Olive oil 5.0
Tocopherol acetate 0.2
Ethylparaben 0.2
Fragrance 0.2
(Phase C)
(N-phenylacetyl) methylalanine 1.0
Sodium bisulfite 0.03
Polyvinyl alcohol (degree of saponification 90, degree of polymerization 2000) 13.0
Ethanol 7.0
Ion exchange water

(Manufacturing method)
A phase, B phase, and C phase were uniformly dissolved, and B phase was added to A phase to solubilize. This was then added to Phase C and mixed.

Formulation Example 120 Peel-off type pack component Amount (% by mass)
(Alcohol phase)
95% ethanol 10.0
POE (15) oleyl alcohol ether 2.0
Preservative Appropriate amount Fragrance Appropriate amount (water phase)
N-benzoyl-L-serine 3.0
Glutathione 3.0
Arbutin 3.0
Polyvinyl alcohol 12.0
PEG 1500 1.0
Ion exchange water

(Manufacturing method)
An aqueous phase was prepared at 80 ° C and cooled to 50 ° C. Subsequently, after adding the alcohol phase prepared at room temperature, it mixed uniformly and allowed to cool.

Formulation Example 121 Powdered pack ingredients Blending amount (% by mass)
(Alcohol phase)
95% ethanol 2.0
Preservative Appropriate amount of perfume Appropriate amount of colorant Appropriate amount
(N-Carbobenzyloxy) methylalanine 3.0
Propylene glycol 7.0
Zinc flower 25.0
Kaolin 20.0
Ion exchange water

(Manufacturing method)
The aqueous phase was uniformly prepared at room temperature. Subsequently, the alcohol phase prepared at room temperature was added and mixed uniformly.

Formulation Example 122 Solid powdery foundation component Amount (% by mass)
(1) Talc 15.0
(2) Sericite 10.0
(3) Spherical nylon powder 10.0
(4) Porous silicic acid powder 15.0
(5) Boron nitride 5.0
(6) Titanium dioxide 5.0
(7) Iron oxide 3.0
(8) Zinc stearate 5.0
(9) (N-phenylacetyl) methylalanine 3.0
(10) Liquid paraffin Residue (11) Triisooctanoic acid glycerin 15.0
(12) Sorbitan sesquioleate 1.5
(13) Preservative appropriate amount (14) Perfume appropriate amount

(Manufacturing method)
To each of the components (1) to (8) mixed and pulverized, a mixture of the components (9) to (14) was added, stirred and mixed, and molded into a container to obtain a solid powdery foundation.

Formulation Example 123 Water-in-oil type emulsified foundation component Amount (% by mass)
(1) Spherical nylon 10.0
(2) Porous silicic acid powder 8.0
(3) Mica titanium 2.0
(4) Silicone-treated sericite 2.0
(5) Silicone-treated mica 12.0
(6) Silicone-treated titanium dioxide 5.0
(7) Silicone-treated iron oxide 2.0
(8) Ion exchange water Residue (9) N-benzoyl-D-alanine 3.0
(10) Decamethylcyclopentanesiloxane 18.0
(11) Dimethylpolysiloxane 5.0
(12) Squalane 1.0
(13) POE-modified dimethylpolysiloxane 2.0
(14) Preservative appropriate amount (15) Fragrance appropriate amount

(Manufacturing method)
The components (9) to (15) were uniformly mixed and dissolved, and then mixed and ground (1) to (7) were added and dispersed. (8) was added to this dispersion and emulsified, and filled into a container to obtain a water-in-oil emulsion foundation.

Claims (7)

A deficiency keratinization inhibitor, a pore reducing agent, or a rough skin prevention / improving agent comprising one or more compounds selected from the group consisting of α-amino acid derivatives represented by the following general formula (1) and salts thereof.

(In General Formula (1), R ₁ and R ₂ are both hydrogen atoms or CH ₃ groups. R ₃ and R ₄ are each independently a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, allyl. Represents a group, a carbobenzyloxy group, an acetyl group, a group represented by the following general formula (2), or a group represented by the following general formula (3), and R ₁ and R ₂ are both hydrogen. When it is an atom and one of R ₃ and R ₄ is a hydrogen atom, one (the other) is a carbobenzyloxy group or a group represented by the following general formula (2).)

(In General Formula (2), X ₁ , X ₂ and X ₃ are each independently an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a hydroxyl group, an amino group, or 1 to 4 carbon atoms. Represents any one of an alkylamino group, a fluorine atom and a trifluoromethyl group, n, m and p each independently represents an integer of 0 to 3, and k and q each independently represents an integer of 0 to 2)

(In general formula (3), X ₁ , X ₂ , X ₃ , k, n, m, and p are the same as in general formula (2).) A deficiency keratinization inhibitor, a pore reducing agent, or a rough skin prevention / improving agent comprising one or more compounds selected from the group consisting of α-amino acid derivatives represented by the following general formula (1) and salts thereof.

(In General Formula (1), R ₁ represents a hydrogen atom or a CH ₃ group, and R ₂ represents a hydrogen atom, a CH ₃ group, or a CH ₂ OH group. However, when R ₁ is a CH ₃ group, R ₂ Represents a hydrogen atom or a CH ₃ group, wherein R ₃ and R ₄ are each independently a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, an allyl group, a carbobenzyloxy group, an acetyl group, represented by the following general formula (2). Any one of R ₃ and R ₄ is a carbobenzyloxy group, a cyclohexanecarbonyl group, a benzoyl group, or a phenylacetyl group. In addition, when one of R ₃ and R ₄ is a carbobenzyloxy group, R ₁ and R ₂ are both hydrogen atoms or both are CH ₃ groups, and R ₁ and R ₂ are both hydrogen. An atom, R ₃ And one of R ₄ is a hydrogen atom, the other (the other) is a carbobenzyloxy group or a group represented by the following general formula (2): _one of R ₁ and R ₂ is a hydrogen atom and the other ( When the other) is a CH ₃ group or when R ₁ is a hydrogen atom and R ₂ is a CH ₂ OH group, one of R ₃ and R ₄ is a group represented by the following general formula (2) or It is a group represented by the formula (3).)

(In General Formula (2), X ₁ , X ₂ and X ₃ are each independently an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a hydroxyl group, an amino group, or 1 to 4 carbon atoms. Represents any one of an alkylamino group, a fluorine atom and a trifluoromethyl group, n, m and p each independently represents an integer of 0 to 3, and k and q each independently represents an integer of 0 to 2)

(In general formula (3), X ₁ , X ₂ , X ₃ , k, n, m, and p are the same as in general formula (2).) The parakeratosis inhibitor, pore-reducing agent, or rough skin preventing / improving agent according to claim 2, wherein in the general formula (1) according to claim 2, either R ₃ or R ₄ is a carbobenzyloxy group. The parakeratosis inhibitor, pore reducing agent, or rough skin preventing / improving agent according to claim 2, wherein either one of R ₃ and R ₄ in the general formula (1) according to claim 2 is a cyclohexanecarbonyl group. _{3. The} keratinization inhibitor, pore reducing agent, or rough skin preventing / improving agent according to claim 2, wherein any one of R ₃ and R ₄ in the general formula (1) according to claim 2 is a benzoyl group. The keratinization inhibitor, pore reducing agent, or rough skin preventing / improving agent according to claim 2, wherein in the general formula (1) according to claim 2, one of R ₃ and R ₄ is a phenylacetyl group. The α-amino acid derivative represented by the general formula (1) is (N-methyl) methylalanine, N-carbobenzyloxyglycine, N-carbobenzyloxysarcosine, (N-carbobenzyloxy) methylalanine, N-acetylsarcosine. (N-acetyl) methylalanine, N-cyclohexanecarbonylglycine, N-cyclohexanecarbonylsarcosine, N-cyclohexanecarbonyl-L-alanine, N-cyclohexanecarbonyl-DL-alanine, N-cyclohexanecarbonyl-D-alanine, (N -Cyclohexanecarbonyl) methylalanine, N-cyclohexanecarbonyl-L-serine, N-cyclohexanecarbonyl-DL-serine, N-cyclohexanecarbonyl-D-serine, N-benzoyl-L-serine, N-be Zoyl-DL-serine, N-benzoyl-L-serine, N-benzoyl-L-alanine, N-benzoyl-DL-alanine, N-benzoyl-D-alanine, (N-benzoyl) methylalanine, N-benzoylsarcosine N-phenylacetyl-L-serine, N-phenylacetyl-DL-serine, N-phenylacetyl-D-serine, N-phenylacetyl-L-alanine, N-phenylacetyl-DL-alanine, N-phenylacetyl The keratinization inhibitor, pore reducing agent, or rough skin preventing / improving agent according to claim 1 or 2, which is any one of -D-alanine, (N-phenylacetyl) methylalanine, and N-phenylacetylsarcosine.