JP2014114234A - Skin external preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a skin external preparation suitable for prevention or improvement of pigmentation.SOLUTION: A skin external preparation contains 1) a compound represented by the following general formula (1), its optical isomer and/or their pharmacologically acceptable salts, and 2) a component having anti-inflammatory activity. In the formula, Ris an unsubstituted aromatic group or an aromatic group having a substituent, Ris a hydrogen atom, a 1-4C straight-chain or branched-chain alkyl group, or a 1-4C straight-chain or branched-chain acyl group having an alkyl chain, and Ris a hydrogen atom or a 1-4C straight-chain or branched-chain alkyl group.

Description

  The present invention relates to skin containing 1) a compound represented by the following general formula (1), an optical isomer thereof and / or a pharmacologically acceptable salt thereof, and 2) a component having an anti-inflammatory action. It relates to an external preparation.

（１）
[式中、Ｒ_１は、無置換又は置換基を有する芳香族基を表し、Ｒ_２は、水素原子、炭素数１〜４の直鎖又は分岐のアルキル基、炭素数１〜４の直鎖又は分岐のアルキル鎖を有するアシル基を表し、Ｒ_３は、水素原子、炭素数１〜４の直鎖又は分岐のアルキル基を表す。]

(1)
[Wherein, R ₁ represents an unsubstituted or substituted aromatic group, R ₂ represents a hydrogen atom, a linear or branched alkyl group having 1 to 4 carbon atoms, or a linear chain having 1 to 4 carbon atoms. Alternatively, it represents an acyl group having a branched alkyl chain, and R ₃ represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms. ]

  Long-term skin irritation such as exposure to ultraviolet rays can cause skin symptoms related to pigmentation such as spots, dullness and darkening of the skin, as well as the formation of wrinkles and sagging, spread of pores, dryness and rough skin. It is known to cause and deeply relate to the skin aging phenomenon. Such exacerbation of skin symptoms and manifestation of the skin aging phenomenon are easy for others to recognize and greatly affect the visual impression. For this reason, for those who are interested in maintaining the beautiful appearance of the skin, the deterioration of the skin symptoms and the manifestation of the skin aging phenomenon can be a big problem.

  For skin symptoms related to pigmentation such as sunburn, blotches and dullness, development of ingredients with pigmentation prevention or improvement has been promoted, and many whitening agents and pigmentation prevention or improvement agents are currently used. (For example, refer nonpatent literature 1). The cosmetics containing the above-mentioned components having a pigmentation preventing or improving action have a certain effect on skin symptoms related to pigmentation. However, it is difficult to say that the effect is expected and satisfied by the user. Therefore, a new chemical structure, a component having a new whitening mechanism, a pigmentation preventing or improving action, a natural material originating from plants, animals, etc., a natural product contained in the natural material, a synthetic compound Material search has been conducted on a wide range of resources such as. In addition, in the current situation where it is becoming difficult to search for new materials, improvement of the whitening effect by using a plurality of active ingredients in combination, improvement of the formulation to improve the whitening effect by improving skin retention and pharmacokinetics, etc. Various attempts are being made actively.

  Anti-inflammatory agents are widely used to suppress inflammatory reactions in the body and relieve skin symptoms such as itching and pain. As anti-inflammatory agents, in addition to plant extracts having an anti-inflammatory effect, components isolated from plant extracts and the like have been found and used for quasi-drugs, cosmetics and the like. As the component having such an anti-inflammatory action, “licorice (licorice)” which is a perennial plant of the leguminous family, and glycyrrhetic acid derivatives and glycyrrhizic acid derivatives which are active ingredients thereof are well known. Some components having anti-inflammatory activity are used as anti-inflammatory analgesics for the treatment of allergic rhinitis, rhinitis, and gastric ulcers (see, for example, Patent Document 1). In addition to the anti-inflammatory-related effects, the glycyrrhetinic acid derivatives have been reported to have antiviral effects (see, for example, Patent Document 2), melanin production inhibitory effects (for example, see Patent Document 3), cosmetics, It is blended in quasi drugs. However, it cannot be said that the effect of the external preparation for skin containing a component having an anti-inflammatory action such as a glycyrrhetinic acid derivative is sufficiently satisfactory. Furthermore, many components having anti-inflammatory effects have problems in stability and safety. For this reason, the technique which prevents or improves the skin symptom in which an inflammatory symptom is concerned was calculated | required by utilizing safely and effectively the biological activity of the component which has an anti-inflammatory action including a glycyrrhetic acid derivative.

On the other hand, there are naturally about 20 types of α-amino acids that constitute proteins of biologically functional molecules called essential amino acids. Essential amino acids are reported not only to be constituents of living organisms but also to have various biological activities. In general, amino acid derivatives having an essential amino acid as a basic skeleton are expected to have high biological activity and safety, and are actively researched and developed. Among the essential amino acids, in particular, serine has been reported to have biological activities such as a rough skin improving action (see, for example, Patent Document 4) and a whitening action (see, for example, Patent Document 5). Furthermore, serine derivatives having a serine as a basic skeleton, for example, N-methyl-L-serine, dermal hyaluronic acid production promoting action (for example, see Patent Document 6), whitening action (for example, Patent Document 7) O-acylserine has been reported to have biological activity such as deodorizing action. Among the serine derivatives, with respect to the N- (benzoyl) serine derivative represented by the general formula (1), pigmentation prevention or improvement action (for example, see Patent Document 8), rough skin prevention or improvement action Pharmacological actions such as wrinkle improving action (see, for example, Patent Document 10) are known (for example, see Patent Document 9).

JP-A-63-135351 JP 2009-511511 A JP 2004-300048 A Japanese Patent Laid-Open No. 06-279227 Japanese Patent Laid-Open No. 05-032533 Japanese Patent Application Laid-Open No. 2004-075646 JP 2000-297025 A WO20111074643 Publication JP 2006-327972 A WO2007034750 gazette

Usefulness of cosmetics Advances in evaluation technology and future prospects, Yakuji Nippo, Katsuyuki Takeda et al., Chapter 1 Usefulness of skincare cosmetics

  This invention is made | formed under such a condition, and makes it a subject to provide the skin external preparation suitable for the pigmentation prevention or improvement.

As a result of intensive efforts to find a skin external preparation suitable for preventing or improving pigmentation, the present inventor has 1) the compound represented by the general formula (1), its optical isomer and / or their drug. By containing both a physically acceptable salt and 2) a component having an anti-inflammatory action in a skin external preparation, the melanin production inhibitory action of the compound represented by the general formula (1) is effectively improved. As a result, the present invention has been completed. That is, the present invention is as follows.
<1> A skin external preparation containing a compound represented by the following general formula (1), an optical isomer thereof and / or a pharmacologically acceptable salt thereof, and 2) a component having an anti-inflammatory action.

（１）
[式中、Ｒ_１は、無置換又は置換基を有する芳香族基を表し、Ｒ_２は、水素原子、炭素数１〜４の直鎖又は分岐のアルキル基、炭素数１〜４の直鎖又は分岐のアルキル鎖を有するアシル基を表し、Ｒ_３は、水素原子、炭素数１〜４の直鎖又は分岐のアルキル基を表す。]

(1)
[Wherein, R ₁ represents an unsubstituted or substituted aromatic group, R ₂ represents a hydrogen atom, a linear or branched alkyl group having 1 to 4 carbon atoms, or a linear chain having 1 to 4 carbon atoms. Alternatively, it represents an acyl group having a branched alkyl chain, and R ₃ represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms. ]

<2> The compound represented by the general formula (1) is a compound represented by the following general formula (2), an optical isomer thereof and / or a pharmacologically acceptable salt thereof, <1 > The external preparation for skin described in>.

（２）
[式中、Ｒ_４は、無置換又は置換基を有する芳香族基を表し、Ｒ_５は、水素原子、炭素数１〜４の直鎖又は分岐のアルキル基、炭素数１〜４の直鎖又は分岐のアルキル鎖を有するアシル基を表す。]

(2)
[Wherein, R ₄ represents an unsubstituted or substituted aromatic group, R ₅ represents a hydrogen atom, a linear or branched alkyl group having 1 to 4 carbon atoms, or a linear chain having 1 to 4 carbon atoms. Alternatively, it represents an acyl group having a branched alkyl chain. ]

<3> The compound represented by the general formula (1) is a compound represented by the following general formula (3), an optical isomer thereof and / or a pharmacologically acceptable salt thereof, <1 > The external preparation for skin described in>.

（３）
[式中、Ｒ_６は、無置換又は置換基を有する芳香族基を表し、Ｒ_７は、水素原子、炭素数１〜４の直鎖又は分岐のアルキル基を表す。]

(3)
[Wherein R ₆ represents an unsubstituted or substituted aromatic group, and R ₇ represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms. ]

<4> The compound represented by the general formula (1) is a compound represented by the following general formula (4), an optical isomer thereof and / or a pharmacologically acceptable salt thereof, <1 > The external preparation for skin described in>.

（４）
[式中、Ｒ_８は、無置換又は置換基を有する芳香族基を表す。]

(4)
[Wherein R ₈ represents an unsubstituted or substituted aromatic group. ]

<5> The compound represented by the general formula (1) is N- (p-methylbenzoyl) serine (compound 1), N- (p-ethylbenzoyl) serine (compound 2), N- (p-methoxy). Benzoyl) serine (compound 3), N- (p-fluorobenzoyl) serine (compound 4), N- (p-trifluoromethylbenzoyl) serine (compound 5), N- (2-naphthoyl) serine (compound 6) N- (4-phenylbenzoyl) serine (compound 7), N- (benzoyl) serine (compound 8), N- (p-methylbenzoyl) serine methyl ester (compound 9), N- (2-naphthoyl) serine Methyl ester (compound 10), N-benzoyl-O-methylserine (compound 11), N- (p-methylbenzoyl) -O-methylserine (compound 12), N- (p-methylbenzoyl) -O- Skin external application according to <1>, which is cetylserine (compound 13), N- (2-naphthoyl) -O-methylserine (compound 14), an optical isomer thereof and / or a pharmacologically acceptable salt thereof. Agent.

N−（p−メチルベンゾイル）セリン（化合物１）

N- (p-methylbenzoyl) serine (Compound 1)

N−（p−エチルベンゾイル）セリン（化合物２）

N- (p-ethylbenzoyl) serine (compound 2)

N−（p−メトキシベンゾイル）セリン（化合物３）

N- (p-methoxybenzoyl) serine (compound 3)

N−（p−フルオロベンゾイル）セリン（化合物４）

N- (p-fluorobenzoyl) serine (compound 4)

N−（p−トリフルオロメチルベンゾイル）セリン（化合物５）

N- (p-trifluoromethylbenzoyl) serine (compound 5)

N−（２−ナフトイル）セリン（化合物６）

N- (2-naphthoyl) serine (Compound 6)

N−（４−フェニルベンゾイル）セリン（化合物７）

N- (4-Phenylbenzoyl) serine (Compound 7)

N−（ベンゾイル）セリン（化合物８）

N- (benzoyl) serine (compound 8)

N−（p−メチルベンゾイル）セリン メチルエステル（化合物９）

N- (p-methylbenzoyl) serine methyl ester (compound 9)

N−（２−ナフトイル）セリン メチルエステル（化合物１０）

N- (2-naphthoyl) serine methyl ester (compound 10)

N−ベンゾイル−O−メチルセリン（化合物１１）

N-benzoyl-O-methylserine (compound 11)

N−（p−メチルベンゾイル）−O−メチルセリン（化合物１２）

N- (p-methylbenzoyl) -O-methylserine (compound 12)

N−（p−メチルベンゾイル）−O−アセチルセリン（化合物１３）

N- (p-methylbenzoyl) -O-acetylserine (compound 13)

N−（２−ナフトイル）−O−メチルセリン（化合物１４）

N- (2-naphthoyl) -O-methylserine (Compound 14)

<6> 0.001% by mass to 10% by mass of the compound represented by the general formula (1), an optical isomer thereof and / or a pharmacologically acceptable salt thereof with respect to the total amount of the external preparation for skin. The external preparation for skin according to any one of <1> to <5>.
<7> The component having an anti-inflammatory action is obtained from a plant extract obtained from a plant belonging to the genus Camellia belonging to the family Asteraceae, a plant extract obtained from a plant belonging to the genus Asteraceae, or a plant belonging to the genus Clara family Plant extract, plant extract obtained from a plant belonging to the genus Birchaceae, plant extract obtained from a plant belonging to the walnut family, plant extract obtained from a plant belonging to the legume family, glycyrrhetinic acid derivative and / or The skin external preparation according to any one of <1> to <6>, which is one or more selected from the salt, the grabridine derivative and / or the salt thereof.
<8> A plant belonging to the genus Camellia belonging to the family Asteraceae, a plant belonging to the genus Burdaceae, a plant belonging to the genus Clara, a plant belonging to the birch family Birch, a plant belonging to the walnut family, and a plant belonging to the legume genus , Asteraceae chamomile genus chamomile (chamomile), asteraceae burdock burdock, leguminous clara kujin, birch family birch birch, walnut family colander, leguminous licorice Agent.
<9> The glycyrrhetinic acid derivative is one or more selected from glycyrrhetinic acid and salts thereof, alkyl glycyrrhetinate and salts thereof, glycyrrhizic acid and salts thereof, and any one of <1> to <8> The skin external preparation described in 1.
<10> The external skin preparation according to any one of <1> to <9>, wherein the component having an anti-inflammatory action is contained in an amount of 0.00001% by mass to 15% by mass with respect to the total amount of the external skin preparation.
<11> The external preparation for skin according to any one of <1> to <10>, which is a cosmetic (including quasi-drugs).
<12> The external preparation for skin according to any one of <1> to <11>, which is for preventing or improving pigmentation.

ADVANTAGE OF THE INVENTION According to this invention, the skin external preparation suitable for the pigmentation prevention or improvement can be provided.

  The skin external preparation of the present invention includes 1) a compound represented by the above general formula (1), an optical isomer thereof and / or a pharmacologically acceptable salt thereof, and 2) a component having an anti-inflammatory action. It is characterized by containing. Moreover, the skin external preparation of this invention is a skin external preparation suitable for the prevention or improvement of pigmentation. The effect of preventing or improving the pigmentation of the external preparation for skin of the present invention can be applied without particular limitation as long as it is an effect of preventing or improving the pigmentation symptoms in the skin. In addition to the effect of preventing or improving pigmentation caused by the usual sunburn that occurs, it also includes the effect of preventing or improving pigmentation symptoms accompanied by irritable spots, dullness, and mild inflammation or rough skin. Sunburn caused by exposure to ultraviolet rays or the like is a transient or reversible pigmentation symptom caused by increased melanin production of pigment cells (melanocytes). On the other hand, when skin irritation due to UV exposure is excessive, or when skin irritation is applied over a long period of time, melanin production of pigment cells is excessively and / or chronically enhanced. Eventually, pigmentation symptoms accompanied by incurable healing, dullness, inflammation and rough skin will be exhibited. The above-described excess of pigment cells and / or chronic increased melanin production induces phenomena such as excessive transport, accumulation or delayed discharge of produced melanin to keratinocytes (cells of keratinocytes). It causes a pigmentation abnormality due to functional deterioration and turnover delay. In the process in which such pigmentation abnormality occurs, various information transmission factors typified by cytokines are involved, and it is often accompanied by rough skin symptoms such as inflammation and / or delamination. The external preparation for skin of the present invention can be expected to have an excellent preventive or ameliorating effect on abnormal pigmentation accompanied by inflammation and rough skin in addition to the above-mentioned normal pigmentation symptoms. Moreover, the skin external preparation of this invention has the compound represented by the said General formula (1), its optical isomer and / or those pharmacologically acceptable salt, and the component which has an anti-inflammatory action. Biological activity can be expected to have an excellent moisturizing effect, an effect of preventing or improving wrinkle formation, and an effect of preventing or improving rough skin such as acne.

  The following are essential components of the external preparation for skin of the present invention: 1) the compound represented by the general formula (1), optical isomers thereof and / or pharmacologically acceptable salts thereof, and 2 ) A component having an anti-inflammatory action will be described.

<The compound represented by the general formula (1) of the present invention, its optical isomer and / or pharmacologically acceptable salt thereof>
The compound represented by the general formula (1) of the present invention, optical isomers thereof and / or pharmacologically acceptable salts thereof may be contained in a skin external preparation together with a component having an anti-inflammatory action described later. By this, the melanin production inhibitory action which the compound represented by the said General formula (1) has is effectively strengthened, and the outstanding pigmentation prevention or improvement effect is exhibited. The compound represented by the general formula (1) of the present invention, its optical isomer and / or pharmacologically acceptable salt thereof is a serine derivative containing serine which is an essential amino acid in the basic skeleton, and a dye. In addition to preventing or improving deposition, it has high safety. In particular, it is excellent in skin safety such as skin sensitization and skin irritation. Furthermore, the compound represented by the general formula (1), optical isomers thereof and / or pharmacologically acceptable salts thereof can be produced at a lower cost than serine and derivatives thereof. In addition, the compound represented by the general formula (1) is highly soluble in general-purpose bases used when producing a skin external preparation such as cosmetics, especially water, a lower alcohol, a polyvalent alcohol. Because of its high solubility in polar bases such as rutile, various forms of external skin preparations can be produced. In addition, the external preparation for skin of the present invention comprises both a compound represented by the general formula (1), an optical isomer thereof and / or a pharmacologically acceptable salt thereof, and a component having an anti-inflammatory action. Inclusion in an external preparation enables preferable pharmacological and pharmacokinetic behavior, and an additive or synergistic effect is enhanced as compared with the case where each component is contained alone.

  The compound represented by the general formula (1) of the present invention, optical isomers thereof and / or pharmacologically acceptable salts thereof are selected from one or more of these components for external use on the skin. It can be contained in the agent. Among the compounds represented by the general formula (1) of the present invention, optical isomers thereof and / or pharmacologically acceptable salts thereof, preferred are the general formulas (2) to (4). And the compounds represented by the formula (1), optical isomers thereof and / or pharmacologically acceptable salts thereof. Furthermore, among the compounds represented by the general formulas (1) to (4), specific examples of preferred compounds include N- (p-methylbenzoyl) serine (compound 1), N- (p-ethylbenzoyl). ) Serine (compound 2), N- (p-methoxybenzoyl) serine (compound 3), N- (p-fluorobenzoyl) serine (compound 4), N- (p-trifluoromethylbenzoyl) serine (compound 5) N- (2-naphthoyl) serine (compound 6), N- (4-phenylbenzoyl) serine (compound 7), N- (benzoyl) serine (compound 8), N- (p-methylbenzoyl) serine methyl ester (Compound 9), N- (2-naphthoyl) serine methyl ester (Compound 10), N-benzoyl-O-methylserine (Compound 11), N- (p-methylbenzoyl) -O-methylserine Compound 12), N- (p-methylbenzoyl) -O-acetylserine (compound 13), N- (2-naphthoyl) -O-methylserine (compound 14), its optical isomers and / or their pharmacological properties Suitable examples of the salts are acceptable. Among the compounds represented by the general formulas (1) to (4), optical isomers thereof and / or pharmacologically acceptable salts thereof, in particular, compounds 1 to 14, optical isomers thereof and / or These pharmacologically acceptable salts exhibit an excellent effect of preventing or improving pigmentation by being contained in an external preparation for skin together with a component having an anti-inflammatory action described later. The compound represented by the general formula (1) of the present invention is an optically active compound having an asymmetric carbon in its chemical structure. For this reason, in the compound represented by the general formula (1), the optically active form of L form or D form, racemic form of 1: 1 mixture of L form and D form, L form and D form are in any ratio. It is possible to exist in various forms such as a mixture mixed together. The compound represented by the general formula (1) of the present invention includes all possible forms such as the optically active form, the racemic form, and a mixture of optically active forms in any ratio. Further, the existence form of the compound represented by the general formula (1) of the present invention is not particularly limited, but from the viewpoint of expression of pharmacological action, safety, solubility, stability, and the like, the optically active substance Furthermore, it is preferable to select and use L-form.

The compound represented by the general formula (1) of the present invention will be described. In the formula, R ₁ represents an unsubstituted or substituted aromatic group, and R ₂ represents a hydrogen atom, a linear or branched alkyl group having 1 to 4 carbon atoms, a linear chain having 1 to 4 carbon atoms, or An acyl group having a branched alkyl chain is represented, and R ₃ represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms. R ₁ represents an unsubstituted or substituted aromatic group, and among the substituents on the aromatic ring in R ₁ , a linear or branched alkyl group having 1 to 4 carbon atoms is preferable. , An alkoxy group having a linear or branched alkyl chain having 1 to 4 carbon atoms, a hydroxyl group, an amino group, a mono or dialkylamino group having a linear or branched alkyl chain having 1 to 4 carbon atoms, a halogen atom, a carbon number Preferable examples include 1 to 4 halogenated alkyl groups, carboxyl groups, ester groups having a linear or branched alkyl chain having 1 to 4 carbon atoms, and unsubstituted or substituted phenyl groups. In addition, the number of substituents on the aromatic ring in R ₁ is not particularly limited, but the number of substituents is preferably 0 to 3, more preferably 0 or 1. Further, the substitution position of the substituent on the aromatic ring is not particularly limited, but it is particularly preferable that the substitution position exists in the para position with respect to the amide bond to which the serine structure on the aromatic ring is bonded. Further, the substituents can be present independently. As the aromatic ring in R ₁ , any aromatic hydrocarbon group or heteroaromatic hydrocarbon group can be applied without particular limitation, and in particular, a phenyl group, a naphthyl group, an imidazole group, a pyridyl group, a quinolyl group. A group etc. can be illustrated suitably. Specific examples of preferred R ₁ include phenyl, methylphenyl, ethylphenyl, propylphenyl, butylphenyl, methoxyphenyl, ethoxyphenyl, propyloxyphenyl, butyloxyphenyl, Hydroxyphenyl group, aminophenyl group, N- (methylamino) phenyl group, N- (ethylamino) phenyl group, N- (propylamino) phenyl group, N- (butylamino) phenyl group, N, N- (dimethyl) Amino) phenyl group, N, N- (diethylamino) phenyl group, N, N- (dipropylamino) phenyl group, N, N- (dibutylamino) phenyl group, acetylphenyl group, propionylphenyl group, butyrylphenyl group , Methoxycarbonylphenyl group, ethoxycarbonylphenyl group, propyloxy Sicarbonylphenyl group, butyloxycarbonylphenyl group, fluorophenyl group, chlorophenyl group, bromophenyl group, trifluoromethylphenyl group, pyridyl group, methylpyridyl group, ethylpyridyl group, propylpyridyl group, butylpyridyl group, methoxypyridyl group , Ethoxypyridyl group, propyloxypyridyl group, butyloxypyridyl group, hydroxypyridyl group, aminopyridyl group, N- (methylamino) pyridyl group, N- (ethylamino) pyridyl group, N- (propylamino) pyridyl group, N- (butylamino) pyridyl group, N, N- (dimethylamino) pyridyl group, N, N- (diethylamino) pyridyl group, N, N- (dipropylamino) pyridyl group, N, N- (dibutylamino) Pyridyl group, acetylpyridyl group, propionyl pyridi Group, butyrylpyridyl group, methoxycarbonylpyridyl group, ethoxycarbonylpyridyl group, propyloxycarbonylpyridyl group, butyloxycarbonylpyridyl group, fluoropyridyl group, chloropyridyl group, bromopyridyl group, trifluoromethylpyridyl group, naphthyl group, Methyl naphthyl group, ethyl naphthyl group, propyl naphthyl group, butyl naphthyl group, methoxy naphthyl group, ethoxy naphthyl group, propyloxy naphthyl group, butyloxy naphthyl group, N- (methylamino) naphthyl group, N- (ethylamino) naphthyl Group, N- (propylamino) naphthyl group, N- (butylamino) naphthyl group, N, N- (dimethylamino) naphthyl group, N, N- (diethylamino) naphthyl group, N, N- (dipropylamino) Naphthyl group, N, N- (dibutyl Mino) naphthyl, acetylnaphthyl, propionylnaphthyl, butyrylnaphthyl, methoxycarbonylnaphthyl, ethoxycarbonylnaphthyl, propyloxycarbonylnaphthyl, butyloxycarbonylnaphthyl, fluoronaphthyl, chloronaphthyl, bromonaphthyl Group, trifluoromethylnaphthyl group, hydroxynaphthyl group, aminonaphthyl group, biphenyl group, (toluyl) phenyl group, (ethylphenyl) phenyl group, (propylphenyl) phenyl group, (butylphenyl) phenyl group, (methoxyphenyl) Phenyl group, (ethoxyphenyl) phenyl group, (propyloxyphenyl) phenyl group, (butyloxyphenyl) phenyl group, (hydroxyphenyl) phenyl group, (aminophenyl) phenyl Group, [N- (methylamino) phenyl] phenyl group, [N- (ethylamino) phenyl] phenyl group, [N- (propylamino) phenyl] phenyl group, [N- (butylamino) phenyl] phenyl group, [N, N- (dimethylamino) phenyl] phenyl group, [N, N- (diethylamino) phenyl] phenyl group, [N, N- (dipropylamino) phenyl] phenyl group, [N, N- (dibutylamino) ) Phenyl] phenyl group, (acetylphenyl) phenyl group, (propionylphenyl) phenyl group, (butyrylphenyl) phenyl group, (methoxycarbonylphenyl) phenyl group, (ethoxycarbonylphenyl) phenyl group, (propyloxycarbonylphenyl) Phenyl group, (butyloxycarbonylphenyl) phenyl group, (fluorophenyl) phenyl group, (chlorophenyl) Phenyl), phenyl group, (bromophenyl) phenyl group, (trifluoromethylphenyl) phenyl group, and the like. Preferred examples include phenyl group, methylphenyl group, ethylphenyl group, methoxyphenyl group, and ethoxyphenyl. Group, fluorophenyl group, trifluoromethylphenyl group, naphthyl group, biphenyl group can be suitably exemplified, and more preferably, 4-methylphenyl group, 4-ethylphenyl group, 4-methoxyphenyl group, 4-fluorophenyl group , 4-trifluoromethylphenyl group, phenyl group, 2-naphthyl group, 4-biphenyl group. R ₂ represents a hydrogen atom, a linear or branched alkyl group having 1 to 4 carbon atoms, or an acyl group having a linear or branched alkyl chain having 1 to 4 carbon atoms. , Methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, acetyl group, propionyl group, butyryl group and the like can be suitably exemplified, and more preferably Can be preferably exemplified by a hydrogen atom, a methyl group, an ethyl group and an acetyl group. R ₃ represents a hydrogen atom, a linear or branched alkyl group having 1 to 4 carbon atoms, and specific examples include a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, an isobutyl group, and n-butyl. Group, isobutyl group, sec-butyl group, tert-butyl group and the like can be preferably exemplified, and more preferably, a hydrogen atom and a methyl group can be suitably exemplified.

The compound represented by the general formula (2) will be described. In the formula, R ₄ represents an unsubstituted or substituted aromatic group, and R ₅ represents a hydrogen atom, a linear or branched alkyl group having 1 to 4 carbon atoms, a linear chain having 1 to 4 carbon atoms, or An acyl group having a branched alkyl chain is represented. R ₄ represents an aromatic group having no substituent or a substituent, and the same substituent as R _{1 in the} compound represented by the general formula (1) can be preferably exemplified. Of these substituents, preferred are phenyl, methylphenyl, ethylphenyl, methoxyphenyl, ethoxyphenyl, fluorophenyl, trifluoromethylphenyl, naphthyl, and biphenyl. More preferably, a phenyl group, 4-methylphenyl group, 4-ethylphenyl group, 4-methoxyphenyl group, 4-fluorophenyl group, 4-trifluoromethylphenyl group, 2-naphthyl group, 4-biphenyl are more preferable. A group can be preferably exemplified. The R ₅ represents a hydrogen atom, a linear or branched alkyl group having 1 to 4 carbon atoms, or an acyl group having a linear or branched alkyl chain having 1 to 4 carbon atoms. , Methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, acetyl group, propionyl group, butyryl group and the like can be suitably exemplified, and more preferably Are preferably a hydrogen atom, a methyl group, or an acetyl group. Specific examples of the compound represented by the general formula (2) that are not included in the compound represented by the general formula (4) include N-benzoyl-O-methylserine, N- (methyl Benzoyl) -O-methylserine, N- (ethylbenzoyl) -O-methylserine, N- (propylbenzoyl) -O-methylserine, N- (methoxybenzoyl) -O-methylserine, N- (ethoxybenzoyl) -O-methylserine N- (propyloxybenzoyl) -O-methylserine, N- (hydroxybenzoyl) -O-methylserine, N- (aminobenzoyl) -O-methylserine, N- (bromobenzoyl) -O-methylserine, N- (chloro Benzoyl) -O-methylserine, N- (fluorobenzoyl) -O-methylserine, N- (trifluoromethylbenzoyl) -O-methylseri N- (pyridinecarbonyl) -O-methylserine, N- (methylpyridinecarbonyl) -O-methylserine, N- (ethylpyridinecarbonyl) -O-methylserine, N- (methoxypyridinecarbonyl) -O-methylserine, N- (Ethoxypyridinecarbonyl) -O-methylserine, N- (naphthoyl) -O-methylserine, N- (methylnaphthoyl) -O-methylserine, N- (ethylnaphthoyl) -O-methylserine, N- (methoxynaphthoyl) ) -O-methylserine, N- (ethoxynaphthoyl) -O-methylserine, N- (biphenylcarbonyl) -O-methylserine, N- (methylbiphenylcarbonyl) -O-methylserine, N- (ethylbiphenylcarbonyl) -O -Methylserine, N- (methoxybiphenylcarbonyl) -O-methylserine, N- (ethoxy Phenylcarbonyl) -O-methylserine, N-benzoyl-O-ethylserine, N- (methylbenzoyl) -O-ethylserine, N- (ethylbenzoyl) -O-ethylserine, N- (propylbenzoyl) -O-ethylserine, N -(Methoxybenzoyl) -O-ethylserine, N- (ethoxybenzoyl) -O-ethylserine, N- (propyloxybenzoyl) -O-ethylserine, N- (hydroxybenzoyl) -O-ethylserine, N- (aminobenzoyl) -O-ethylserine, N- (bromobenzoyl) -O-ethylserine, N- (chlorobenzoyl) -O-ethylserine, N- (fluorobenzoyl) -O-ethylserine, N- (trifluoromethylbenzoyl) -O-ethylserine N- (pyridinecarbonyl) -O-ethylserine, N- (methylpyridine cal Nyl) -O-ethylserine, N- (ethylpyridinecarbonyl) -O-ethylserine, N- (methoxypyridinecarbonyl) -O-ethylserine, N- (ethoxypyridinecarbonyl) -O-ethylserine, N- (naphthoyl) -O -Ethylserine, N- (methylnaphthoyl) -O-ethylserine, N- (ethylnaphthoyl) -O-ethylserine, N- (methoxynaphthoyl) -O-ethylserine, N- (ethoxynaphthoyl) -O-ethylserine N- (biphenylcarbonyl) -O-ethylserine, N- (methylbiphenylcarbonyl) -O-ethylserine, N- (ethylbiphenylcarbonyl) -O-ethylserine, N- (methoxybiphenylcarbonyl) -O-ethylserine, N- (Ethoxybiphenylcarbonyl) -O-ethylserine, N-benzoyl-O-acetylseri N- (methylbenzoyl) -O-acetylserine, N- (ethylbenzoyl) -O-acetylserine, N- (propylbenzoyl) -O-acetylserine, N- (methoxybenzoyl) -O-acetylserine, N -(Ethoxybenzoyl) -O-acetylserine, N- (propyloxybenzoyl) -O-acetylserine, N- (hydroxybenzoyl) -O-acetylserine, N- (aminobenzoyl) -O-acetylserine, N- (Bromobenzoyl) -O-acetylserine, N- (chlorobenzoyl) -O-acetylserine, N- (fluorobenzoyl) -O-acetylserine, N- (trifluoromethylbenzoyl) -O-acetylserine, N- (Pyridinecarbonyl) -O-acetylserine, N- (methylpyridinecarbonyl) -O-acetylserine, N- (ethylpyriline) Gincarbonyl) -O-acetylserine, N- (methoxypyridinecarbonyl) -O-acetylserine, N- (ethoxypyridinecarbonyl) -O-acetylserine, N- (naphthoyl) -O-acetylserine, N- (methyl Naphthoyl) -O-acetylserine, N- (ethylnaphthoyl) -O-acetylserine, N- (methoxynaphthoyl) -O-acetylserine, N- (ethoxynaphthoyl) -O-acetylserine, N- (Biphenylcarbonyl) -O-acetylserine, N- (methylbiphenylcarbonyl) -O-acetylserine, N- (ethylbiphenylcarbonyl) -O-acetylserine, N- (methoxybiphenylcarbonyl) -O-acetylserine, N -(Ethoxybiphenylcarbonyl) -O-acetylserine, N-benzoyl-O-propionylserine, N- (me Tylbenzoyl) -O-propionylserine, N- (ethylbenzoyl) -O-propionylserine, N- (propylbenzoyl) -O-propionylserine, N- (methoxybenzoyl) -O-propionylserine, N- (ethoxybenzoyl) ) -O-propionylserine, N- (propyloxybenzoyl) -O-propionylserine, N- (hydroxybenzoyl) -O-propionylserine, N- (aminobenzoyl) -O-propionylserine, N- (bromobenzoyl) -O-propionylserine, N- (chlorobenzoyl) -O-propionylserine, N- (fluorobenzoyl) -O-propionylserine, N- (trifluoromethylbenzoyl) -O-propionylserine, N- (pyridinecarbonyl) -O-propionylserine, N- (methylpyridine cal Nyl) -O-propionylserine, N- (ethylpyridinecarbonyl) -O-propionylserine, N- (methoxypyridinecarbonyl) -O-propionylserine, N- (ethoxypyridinecarbonyl) -O-propionylserine, N- ( Naphthoyl) -O-propionylserine, N- (methylnaphthoyl) -O-propionylserine, N- (ethylnaphthoyl) -O-propionylserine, N- (methoxynaphthoyl) -O-propionylserine, N- ( Ethoxynaphthoyl) -O-propionylserine, N- (biphenylcarbonyl) -O-propionylserine, N- (methylbiphenylcarbonyl) -O-propionylserine, N- (ethylbiphenylcarbonyl) -O-propionylserine, N- (Methoxybiphenylcarbonyl) -O-propionylserine, N- ( Butoxy biphenylcarbonyl) -O- propionyl serine, its optical isomers and / or their pharmacologically acceptable salts are suitably be exemplified. Among the compounds represented by the general formula (2), more preferable compounds include N- (methylbenzoyl) serine, N- (ethylbenzoyl) serine, N- (methoxybenzoyl) serine, N- (fluorobenzoyl). ) Serine, N- (trifluoromethylbenzoyl) serine, N- (naphthoyl) serine, N- (phenylbenzoyl) serine, N- (benzoyl) serine, N-benzoyl-O-methylserine, N- (methylbenzoyl)- Preferable examples include O-methylserine, N- (methylbenzoyl) -O-acetylserine, N- (naphthoyl) -O-methylserine, optical isomers thereof and / or pharmacologically acceptable salts thereof. Preferably, N- (p-methylbenzoyl) serine (compound 1), N- (p-ethylbenzoyl) serine (compound 2), N- (p-methoxy) Benzoyl) serine (compound 3), N- (p-fluorobenzoyl) serine (compound 4), N- (p-trifluoromethylbenzoyl) serine (compound 5), N- (2-naphthoyl) serine (compound 6) N- (4-phenylbenzoyl) serine (compound 7), N- (benzoyl) serine (compound 8), N-benzoyl-O-methylserine (compound 11), N- (p-methylbenzoyl) -O-methylserine (Compound 12), N- (p-methylbenzoyl) -O-acetylserine (Compound 13), N- (2-naphthoyl) -O-methylserine (Compound 14), its optical isomers and / or their pharmacology A particularly acceptable salt can be suitably exemplified. Such a compound exhibits an excellent effect of preventing or improving pigmentation by being contained in an external preparation for skin together with a component having an anti-inflammatory action described later.

The compound represented by the general formula (3) will be described. In the formula, R ₆ represents an unsubstituted or substituted aromatic group, and R ₇ represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms. R ₆ represents an aromatic group having no substituent or a substituent, and the same substituent as R ₁ in the compound represented by the general formula (1) can be preferably exemplified. Among these substituents, preferred examples include phenyl, methylphenyl, ethylphenyl, methoxyphenyl, ethoxyphenyl, fluorophenyl, trifluoromethylphenyl, naphthyl, and biphenyl. More preferably, a phenyl group, a 4-methylphenyl group, a 4-ethylphenyl group, a 4-methoxyphenyl group, a 4-fluorophenyl group, a 4-trifluoromethylphenyl group, a 2-naphthyl group, or a 4-biphenyl group. It can illustrate suitably. R ₇ represents a hydrogen atom, a linear or branched alkyl group having 1 to 4 carbon atoms, and specific examples include a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, and n-butyl. Group, isobutyl group, sec-butyl group, tert-butyl group and the like can be preferably exemplified, and more preferably, a hydrogen atom and a methyl group can be suitably exemplified. Specific examples of the compound represented by the general formula (3) that are not included in the compound represented by the general formula (4) include N- (benzoyl) serine methyl ester, N- ( Methyl benzoyl) serine methyl ester, N- (ethylbenzoyl) serine methyl ester, N- (propylbenzoyl) serine methyl ester, N- (methoxybenzoyl) serine methyl ester, N- (ethoxybenzoyl) serine methyl ester, N- ( Propyloxybenzoyl) serine methyl ester, N- (hydroxybenzoyl) serine methyl ester, N- (aminobenzoyl) serine methyl ester, N- (chlorobenzoyl) serine methyl ester, N- (fluorobenzoyl) serine methyl ester, N- (Trifluoromethylbenzoyl) serine Ester, N- (pyridinecarbonyl) serine methyl ester, N- (methylpyridinecarbonyl) serine methyl ester, N- (ethylpyridinecarbonyl) serine methyl ester, N- (methoxypyridinecarbonyl) serine methyl ester, N- (ethoxypyridine) Carbonyl) serine methyl ester, N- (naphthoyl) serine methyl ester, N- (methylnaphthoyl) serine methyl ester, N- (ethylnaphthoyl) serine methyl ester, N- (methoxynaphthoyl) serine methyl ester, N- (Ethoxynaphthoyl) serine methyl ester, N- (phenylbenzoyl) serine methyl ester, N- (methylphenylbenzoyl) serine methyl ester, N- (ethylphenylbenzoyl) serine methyl ester, N- (methoxy) Phenylbenzoyl) serine methyl ester, N- (ethoxyphenylbenzoyl) serine methyl ester, N- (benzoyl) serine ethyl ester, N- (methylbenzoyl) serine ethyl ester, N- (ethylbenzoyl) serine ethyl ester, N- ( Propylbenzoyl) serine ethyl ester, N- (methoxybenzoyl) serine ethyl ester, N- (ethoxybenzoyl) serine ethyl ester, N- (propyloxybenzoyl) serine ethyl ester, N- (hydroxybenzoyl) serine ethyl ester, N- (Aminobenzoyl) serine ethyl ester, N- (chlorobenzoyl) serine ethyl ester, N- (fluorobenzoyl) serine ethyl ester, N- (trifluoromethylbenzoyl) serine ethyl ester N- (pyridinecarbonyl) serine ethyl ester, N- (methylpyridinecarbonyl) serine ethyl ester, N- (ethylpyridinecarbonyl) serine ethyl ester, N- (methoxypyridinecarbonyl) serine ethyl ester, N- (ethoxypyridinecarbonyl) ) Serine ethyl ester, N- (naphthoyl) serine ethyl ester, N- (methylnaphthoyl) serine ethyl ester, N- (ethylnaphthoyl) serine ethyl ester, N- (methoxynaphthoyl) serine ethyl ester, N- ( Ethoxynaphthoyl) serine ethyl ester, N- (phenylbenzoyl) serine ethyl ester, N- (methylphenylbenzoyl) serine ethyl ester, N- (ethylphenylbenzoyl) serine ethyl ester, N- (methoxyphenyl) Nzoyl) serine ethyl ester, N- (ethoxyphenylbenzoyl) serine ethyl ester, N- (benzoyl) serine propyl ester, N- (methylbenzoyl) serine propyl ester, N- (ethylbenzoyl) serine propyl ester, N- (propyl) Benzoyl) serine propyl ester, N- (methoxybenzoyl) serine propyl ester, N- (ethoxybenzoyl) serine propyl ester, N- (propyloxybenzoyl) serine propyl ester, N- (hydroxybenzoyl) serine propyl ester, N- ( Aminobenzoyl) serine propyl ester, N- (chlorobenzoyl) serine propyl ester, N- (fluorobenzoyl) serine propyl ester, N- (trifluoromethylbenzoyl) serine Propyl ester, N- (pyridinecarbonyl) serine propyl ester, N- (methylpyridinecarbonyl) serine propyl ester, N- (ethylpyridinecarbonyl) serine propyl ester, N- (methoxypyridinecarbonyl) serine propyl ester, N- (ethoxypyridine) Carbonyl) serine propyl ester, N- (naphthoyl) serine propyl ester, N- (methylnaphthoyl) serine propyl ester, N- (ethylnaphthoyl) serine propyl ester, N- (methoxynaphthoyl) serine propyl ester, N- (Ethoxynaphthoyl) serine propyl ester, N- (phenylbenzoyl) serine propyl ester, N- (methylphenylbenzoyl) serine propyl ester, N- (ethylphenylbenzoyl) serine Ropiruesuteru, N- (methoxyphenyl benzoyl) serine propyl ester, N- (ethoxyphenyl benzoyl) serine propyl ester, its optical isomers and / or their pharmacologically acceptable salts are suitably be exemplified. Among these compounds represented by the general formula (3), N- (methylbenzoyl) serine, N- (ethylbenzoyl) serine, N- (methoxybenzoyl) serine, N- (fluoro Benzoyl) serine, N- (trifluoromethylbenzoyl) serine, N- (naphthoyl) serine, N- (phenylbenzoyl) serine, N- (benzoyl) serine, N- (methylbenzoyl) serine methyl ester, N- (naphthoyl) ) Serine methyl ester, its optical isomer and / or pharmacologically acceptable salt thereof can be preferably exemplified, and more preferably, N- (p-methylbenzoyl) serine (Compound 1), N- (p -Ethylbenzoyl) serine (compound 2), N- (p-methoxybenzoyl) serine (compound 3), N- (p-fluorobenzoyl) serine ( Compound 4), N- (p-trifluoromethylbenzoyl) serine (compound 5), N- (2-naphthoyl) serine (compound 6), N- (4-phenylbenzoyl) serine (compound 7), N- (Benzoyl) serine (compound 8), N- (p-methylbenzoyl) serine methyl ester (compound 9), N- (2-naphthoyl) serine methyl ester (compound 10), its optical isomers and / or their drugs Physiologically acceptable salts can be preferably exemplified. When such a compound is added to a skin external preparation together with a component having an anti-inflammatory action described below, it exhibits an excellent pigmentation preventing or improving action.

The compound represented by the general formula (4) will be described. In the formula, R ₈ represents an unsubstituted or substituted aromatic group. R ₈ represents an unsubstituted or substituted aromatic group, and the same substituents as R ₁ in the compound represented by the general formula (1) can be preferably exemplified. Among these substituents, preferred examples include phenyl, methylphenyl, ethylphenyl, methoxyphenyl, ethoxyphenyl, fluorophenyl, trifluoromethylphenyl, naphthyl, and biphenyl. More preferably, a phenyl group, a 4-methylphenyl group, a 4-ethylphenyl group, a 4-methoxyphenyl group, a 4-fluorophenyl group, a 4-trifluoromethylphenyl group, a 2-naphthyl group, or a 4-biphenyl group. It can illustrate suitably. Specific examples of preferred compounds among the compounds represented by the general formula (4) include N- (benzoyl) serine, N- (methylbenzoyl) serine, N- (ethylbenzoyl) serine, N- ( Propylbenzoyl) serine, N- (butylbenzoyl) serine, N- (methoxybenzoyl) serine, N- (ethoxybenzoyl) serine, N- (propyloxybenzoyl) serine, N- (butyloxybenzoyl) serine, N- ( Hydroxybenzoyl) serine, N- (aminobenzoyl) serine, N- (N′-methylaminobenzoyl) serine, N- (N′-ethylaminobenzoyl) serine, N- (N ′, N′-dimethylaminobenzoyl) Serine, N- (N ′, N′-diethylaminobenzoyl) serine, N- (chlorobenzoyl) serine, N- (fluorobenzoyl) serine, N- Trifluoromethylbenzoyl) serine, N- (pyridinecarbonyl) serine, N- (methylpyridinecarbonyl) serine, N- (ethylpyridinecarbonyl) serine, N- (propylpyridinecarbonyl) serine, N- (methoxypyridinecarbonyl) serine N- (ethoxypyridinecarbonyl) serine, N- (propyloxypyridinecarbonyl) serine, N- (hydroxypyridinecarbonyl) serine, N- (aminopyridinecarbonyl) serine, N- (chloropyridinecarbonyl) serine, N- ( Fluoropyridinecarbonyl) serine, N- (trifluoromethylpyridinecarbonyl) serine, N- (naphthoyl) serine, N- (methylnaphthoyl) serine, N- (ethylnaphthoyl) serine, N- (propylnaphthoyl) serine , N- (methoxynaphtho Yl) serine, N- (ethoxynaphthoyl) serine, N- (propyloxynaphthoyl) serine, N- (hydroxynaphthoyl) serine, N- (aminonaphthoyl) serine, N- (chloronaphthoyl) serine, N- (fluoronaphthoyl) serine, N- (trifluoromethylnaphthoyl) serine, N- (phenylbenzoyl) serine, N- (methylphenylbenzoyl) serine, N- (ethylphenylbenzoyl) serine, N- (propyl Phenylbenzoyl) serine, N- (methoxyphenylbenzoyl) serine, N- (ethoxyphenylbenzoyl) serine, N- (propyloxyphenylbenzoyl) serine, N- (hydroxyphenylbenzoyl) serine, N- (aminophenylbenzoyl) serine N- (chlorophenylbenzoyl) serine, N- (fluoro Phenylbenzoyl) serine, N- (trifluoromethylphenylbenzoyl) serine, its optical isomers and / or pharmacologically acceptable salts thereof can be suitably exemplified, and more preferably N- (methylbenzoyl) serine N- (ethylbenzoyl) serine, N- (methoxybenzoyl) serine, N- (fluorobenzoyl) serine, N- (trifluoromethylbenzoyl) serine, N- (naphthoyl) serine, N- (phenylbenzoyl) serine, N- (benzoyl) serine, optical isomers thereof and / or pharmacologically acceptable salts thereof can be preferably exemplified, and more preferably N- (p-methylbenzoyl) serine (compound 1), N- (P-ethylbenzoyl) serine (compound 2), N- (p-methoxybenzoyl) serine (compound 3), N- (p-fluoroben Zoyl) serine (compound 4), N- (p-trifluoromethylbenzoyl) serine (compound 5), N- (2-naphthoyl) serine (compound 6), N- (4-phenylbenzoyl) serine (compound 7) N- (benzoyl) serine (compound 8), optical isomers thereof and / or pharmacologically acceptable salts thereof can be suitably exemplified. When such a compound is added to a skin external preparation together with a component having an anti-inflammatory action described below, it exhibits an excellent pigmentation preventing or improving action.

  The compounds represented by the general formulas (1) to (4), optical isomers thereof and / or pharmacologically acceptable salts thereof start from commercially available serine or a serine derivative, for example, WO20111074643 It can also be produced according to the synthesis method described in No. 1, and further according to the synthesis method described in “Basics and Experiments of Peptide Synthesis (Maruzen)”. Such a compound can be used as it is by adding it to the external preparation for skin of the present invention, but it can also be treated with a pharmacologically acceptable acid or base, converted into a salt form, and used as a salt. . Examples of the pharmacologically acceptable salts of the compounds represented by the general formulas (1) to (4) include mineral salts such as hydrochloride, sulfate, nitrate, phosphate, carbonate, and maleate. Acid, fumarate, oxalate, citrate, lactate, tartrate, methanesulfonate, paratoluenesulfonate, benzenesulfonate, and other organic acid salts, sodium salts, potassium salts, etc. Basic amino acids such as alkaline earth metal salts such as metal salts, calcium salts and magnesium salts, organic amine salts such as triethylamine salts, triethanolamine salts, ammonium salts, monoethanolamine salts and piperidine salts, lysine salts and alginates A salt etc. can be illustrated suitably.

  The skin external preparation of the present invention is one or two selected from the compounds represented by the general formulas (1) to (4), optical isomers thereof and / or pharmacologically acceptable salts thereof. The above can be contained in a skin external preparation. In order for the skin external preparation of the present invention to have an effect of preventing or improving pigmentation, the compounds represented by the general formulas (1) to (4), optical isomers thereof and / or pharmacologically acceptable thereof. 1 to 2 or more types selected from the salts to be used are in a total amount of 0.0001% to 20% by weight, more preferably 0.001% to 10% by weight, based on the total amount of the external preparation for skin. Preferably, the content is 0.005 to 5% by mass. The content of the compound represented by the general formulas (1) to (4), optical isomers thereof and / or pharmacologically acceptable salts thereof with respect to the total amount of the external preparation for skin is 0.0001% by mass. This is because the expression of the pharmacological action tends to decrease if the amount is less, and even if the amount exceeds 20% by mass, the effect tends to reach its peak, and the degree of freedom of formulation may be reduced. Therefore, the content described above with respect to the total amount of the external preparation for skin is preferable.

<Ingredient having anti-inflammatory action of the present invention>
As the component having anti-inflammatory action contained in the external preparation for skin of the present invention, any substance having anti-inflammatory action can be applied without particular limitation. As the component having anti-inflammatory action of the present invention, a plant extract obtained from a plant belonging to the genus Camellia belonging to the family Asteraceae, a plant extract obtained from a plant belonging to the genus Asteraceae, obtained from a plant belonging to the genus Clara family Anti-inflammatory effects such as plant extracts, plant extracts obtained from plants belonging to the genus Birchaceae, plant extracts obtained from plants belonging to the walnut family, plant extracts obtained from plants belonging to the Leguminosae family In addition to plant extracts, clarinone, glabrizine, glycyrrhizic acid and salts thereof, glycyrrhetinic acid and salts thereof, glycyrrhetinic acid derivatives and salts thereof can be preferably exemplified. Among the components having such an anti-inflammatory action, preferred are a plant extract obtained from Camellia chamomile chamomile (chamomile), a plant extract obtained from Asteraceae burdock, and a leguminous clara kujin. Plant extract obtained, plant extract obtained from birch family birch genus birch, plant extract obtained from walnut family Koki, plant extract obtained from legume licorice licorice, glycyrrhizic acid and its salt, glycyrrhetinic acid and its Suitable examples include salts, glycyrrhetinic acid derivatives and salts thereof.

  The plant extract having an anti-inflammatory action of the present invention is added with 1 to 20 times the amount of a plant or a processed product thereof using a lower alcohol such as water or ethanol as a solvent, and if necessary, stirring is appropriately added. After immersion for several days at room temperature or several hours at a temperature near the boiling point, the insoluble matter is removed by filtration or the like, and then the solvent is removed by distillation under reduced pressure or the like. And the like can be fractionated and purified by column chromatography or the like and used. Preferred sites for preparing the plant extract having anti-inflammatory activity of the present invention include flower buds of Camellia genus Chamomile (camomile), roots of Compositae burdock burdock, and Clariaceae In the case of the genus Kujin, the rhizome part, the birch of the birch family Birch genus, the bark, the leaf part of the walnut family Koki, and the rhizome of the licorice licorice can be preferably exemplified. In addition, such plant extracts are commercially available, and can be purchased and used from, for example, Maruzen Pharmaceutical Co., Ltd. Among the glycyrrhetinic acid derivatives such as clarinone, glabrizine, glycyrrhizic acid and its salt, glycyrrhetinic acid and its salt, alkyl glycyrrhetinate and its salt, which are anti-inflammatory components of the present invention, preferred are glycyrrhizic acid and The salt, glycyrrhetinic acid and its salt, stearyl glycyrrhetic acid and its salt can be illustrated suitably, and the component which has such an anti-inflammatory action can be purchased from Wako Pure Chemical Industries Ltd. etc. Moreover, the component which has an anti-inflammatory action of this invention contains the component which has pharmacological effects, such as a whitening effect | action and a moisturizing effect, in addition to an anti-inflammatory effect. The component having such an anti-inflammatory action is excellent when it is contained in a skin external preparation together with the compound represented by the general formula (1), optical isomers thereof and / or pharmacologically acceptable salts thereof. Exhibits or prevents pigmentation. Furthermore, the anti-inflammatory component of this invention can select the 1 type (s) or 2 or more types of the component which has the said anti-inflammatory action, and can be made to contain in the skin external preparation of this invention.

  In general, in skin to which a skin external preparation containing a whitening agent is applied, there is a high possibility that inflammation is caused to some extent by stimulation such as exposure to ultraviolet rays. Melanin production is enhanced and pigmentation is promoted. Therefore, by containing a component having an anti-inflammatory action, in addition to suppressing melanin production enhancement and preventing or improving pigmentation symptoms, it is possible to reduce inflammation or suppress further inflammation. For this reason, when the topical skin preparation of the present invention is administered against skin inflammation observed immediately after sunburn, the pigmentation symptom is improved by suppressing melanin production and the skin barrier function is restored by suppressing inflammation more quickly. Prevent skin condition deterioration. That is, the pigmentation symptom due to skin irritation such as sunburn can be improved, the skin barrier function is lowered due to inflammation and the occurrence of rough skin can be suppressed, and the pigmentation and the accompanying skin symptom can be prevented from worsening. Further, the external preparation for skin of the present invention improves skin moisture and elasticity by improving skin barrier function in addition to skin aging symptoms such as stains and dullness caused by pigmentation symptoms, wrinkles, sagging, etc. Skin aging can be prevented or improved.

  Among the components having anti-inflammatory action contained in the external preparation for skin of the present invention, the plant extract having anti-inflammatory action has the effect of preventing or improving pigmentation. In a total amount of 0.00001% by mass to 15% by mass, more preferably 0.0001% by mass to 10% by mass, and more preferably 0.001% by mass to 5% by mass. This is because when the content of the plant extract having an anti-inflammatory action is too low, the above-mentioned action tends to decrease, and when it is too much, the effect tends to reach its peak, and the degree of freedom of the system is impaired. This is because there exists.

  Among the components having anti-inflammatory activity of the present invention, glycyrrhetinic acid derivatives and salts thereof are components used as active ingredients of quasi drugs. Among the anti-inflammatory components of the present invention, as glycyrrhetinic acid and salts thereof, alkyl glycyrrhetinate and salts thereof can be preferably exemplified, and more preferable examples include stearyl glycyrrhetinate and lauryl glycyrrhetinate, and glycyrrhizin. Preferred examples of the acid and its salt include glycyrrhizic acid, dipotassium glycyrrhizinate and ammonium glycyrrhizinate. Of the glycyrrhetinic acid derivatives and salts thereof and glycyrrhizic acid and salts thereof, particularly preferred are stearyl glycyrrhetinate and dipotassium glycyrrhizinate. Such ingredients have abundant track records of use in quasi-drugs and have been confirmed to be highly effective and safe. Glycyrrhetinic acid derivatives and salts thereof, glycyrrhizic acid and salts thereof, and the like can be purchased from Wako Pure Chemical Industries, Ltd. and used. The preferable content of such components is 0.01% by mass to 3% by mass, more preferably 0.03% by mass to 1% by mass, and still more preferably 0.05 to 0.5% by mass with respect to the total amount of the external preparation for skin. % By mass. This is because if the amount is too small, the effect of preventing or improving pigmentation tends to be reduced, while if too large, the effect tends to reach its peak, and the degree of freedom of this system may be impaired. Among such components, there is also a component that expresses a melanin production inhibitory effect when contained alone in a skin external preparation. In the external preparation for skin of the present invention, an anti-inflammatory component is contained together with the compound represented by the general formula (1), its optical isomer and / or pharmacologically acceptable salt thereof. Thus, compared with the case of single use, it exhibits an excellent effect of preventing or improving pigmentation.

  Among the components having anti-inflammatory activity of the present invention, the plant extract can be produced according to the method for producing a plant extract shown below, or a company handling plant extracts such as Maruzen Pharmaceutical Co., Ltd. You can purchase and use more.

<Production Example 1: Method 1 for producing plant extract having anti-inflammatory action of the present invention>
Rhizome 1 (kg) of leguminous clara genus rhizome was chopped, 10 (L) ethanol was added thereto, heated under reflux for 3 hours with stirring, cooled to room temperature, and concentrated under reduced pressure. . 2 (L) water and 2 (L) ethyl acetate were added to this product, solubilized, and liquid-liquid extraction was performed. The ethyl acetate phase was taken and concentrated to obtain 105 (g) of amorphous. Furthermore, the amorphous 1.2 (g) was dissolved in 8 (L) of 60% 1,3-butanediol aqueous solution to obtain an extract obtained from the leguminous cucumber of the present invention. Moreover, the plant extract which has the anti-inflammatory action of this invention can be manufactured according to the same method. In addition, such a plant extract (solid matter) can be dissolved in anhydrous or hydrous ethanol, anhydrous or hydrous 1,3-butanediol, etc., and used as the plant extract of the present invention.

<Production Example 2: Method 2 for producing plant extract having anti-inflammatory action of the present invention>
Add 5 (L) of 50% ethanol to 500 (g) of the above-ground legume licorice, heat and reflux for 3 hours, filter, concentrate under reduced pressure, freeze-dry, and then freeze-dried Obtained plant extract 124 (g) was obtained.

<Production Example 3: Method 3 for producing plant extract having anti-inflammatory action of the present invention>
Birch bark dry matter 1 (Kg) was chopped, water 10 (L) was added thereto, and the mixture was heated at 90 ° C. for 4 hours. Insoluble matter was removed by filtration and freeze-dried to obtain 1.1 (g) of amorphous plant extract obtained from birch birch genus birch.

<Production Example 4: Method 4 for producing plant extract having anti-inflammatory action of the present invention>
Shredded dried chamomile chamomile chamomile (500 g), added 5 (L) 50% ethanol aqueous solution, heated to reflux for 3 hours, allowed to cool, then filtered to insoluble matter Were removed, concentrated under reduced pressure, and lyophilized to obtain a plant extract obtained from the chamomile chamomile chamomile.

<Skin external preparation of the present invention>
The skin external preparation of the present invention includes 1) a compound represented by the above general formula (1), an optical isomer thereof and / or a pharmacologically acceptable salt thereof, and 2) a component having an anti-inflammatory action. It is characterized by doing. The skin external preparation of the present invention exhibits an excellent effect of preventing or improving pigmentation by containing the essential components. The pigmentation prevention or improvement action targeted by the topical skin preparation of the present invention can be applied without particular limitation as long as it is a pigmentation symptom in the skin. Such pigmentation symptom is usually caused by exposure to ultraviolet rays or the like. In addition to sunburn, etc., it also includes preventive or ameliorating effects on incurable spots, dullness, and pigmentation symptoms accompanied by mild inflammation or rough skin. Moreover, the skin external preparation of this invention can anticipate the prevention or improvement effect outstanding also with respect to the pigmentation abnormality which exhibits the skin symptom in which inflammation, rough skin, etc. are concerned. Furthermore, the pigmentation prevention or improvement action by the external preparation for skin of the present invention is a target based on the above-described pharmacological addition or synergistic effect of the essential ingredients, as well as the improvement of the skin permeability or retention of both ingredients. This is considered to be due to the effect of improving the delivery efficiency of the compound represented by the general formula (1) and / or their pharmacologically acceptable salts and / or anti-inflammatory components to the site. The method for producing a skin external preparation of the present invention comprises a compound represented by the general formula (1), an optical isomer thereof and / or a pharmacologically acceptable salt thereof, and 2) an anti-inflammatory component. If it contains, it will not specifically limit about content (blending amount) of both components, and another structure, and a preparation method is also not specifically limited.

  In formulating the external preparation for skin of the present invention, in addition to the above-mentioned essential components, optional components used in the formulation of ordinary pharmaceuticals, quasi drugs, cosmetics and the like can be contained. Further, when the compound represented by the general formula (1), its optical isomer and / or its pharmacologically acceptable salt, and a component having an anti-inflammatory action are continuously administered together, the effects and In consideration of safety, it is preferably administered transdermally. The external skin preparation of the present invention can be used without particular limitation as long as it is applied externally to the skin, for example, cosmetics, skin external medicine, skin external goods, etc. can be suitably exemplified, It is particularly preferable to apply it as a cosmetic. This is because the external preparation for skin of the present invention has an unparalleled feeling of use and is particularly suitable for cosmetics where the feeling of use is important. Examples of the external preparation for skin of the present invention include preferably lotions such as cosmetics, emulsions, essences, creams, pack cosmetics, facial cleansing cosmetics, cleansing cosmetics and the like. Furthermore, the dosage form is not particularly limited as long as it is known in the cosmetics field, and can be preferably exemplified by lotion preparations, oil-in-water emulsion preparations, water-in-oil emulsion preparations, composite emulsion emulsion preparations and the like.

  In the external preparation for skin of the present invention, in addition to the essential components described above, optional components that are usually used in external preparations for skin can be contained. Examples of such optional ingredients include macadamia nut oil, avocado oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower oil, cottonseed oil, jojoba oil, coconut oil, palm oil, liquid lanolin, and hardened coconut oil. Oil, wax, oils such as beeswax, molasses, hydrogenated castor oil, beeswax, candelilla wax, carnauba wax, ibotarou, lanolin, reduced lanolin, hard lanolin, jojoba wax; , Hydrocarbons such as microcrystalline wax; higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, undecylenic acid; cetyl alcohol, stearyl alcohol, isostearyl Higher alcohols such as alcohol, behenyl alcohol, octyldodecanol, myristyl alcohol, cetostearyl alcohol; cetyl isooctanoate, isopropyl myristate, hexyldecyl isostearate, diisopropyl adipate, di-2-ethylhexyl sebacate, cetyl lactate, malic acid Diisostearyl, di-2-ethylhexanoic acid ethylene glycol, dicaprate neopentyl glycol, di-2-heptylundecanoic acid glycerin, tri-2-ethylhexanoic acid glycerin, tri-2-ethylhexanoic acid trimethylolpropane, tri Synthetic ester oils such as trimethylolpropane isostearate and pentane erythritol tetra-2-ethylhexanoate; dimethylpolysiloxane, methylphenylpoly Linear polysiloxanes such as oxane and diphenylpolysiloxane; cyclic polysiloxanes such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, and dodecamethylcyclohexanesiloxane; amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxane, Oil agents such as silicone oils such as modified polysiloxanes such as fluorine-modified polysiloxanes; Anionic surfactants such as fatty acid soap (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, triethanolamine ether of alkyl sulfates; Cationic surfactants such as stearyltrimethylammonium, benzalkonium chloride, laurylamine oxide; imidazoline-based amphoteric surfactants (2-cocoyl-2-imida Zolinium hydroxide-1-carboxyethyloxy disodium salt, etc.), betaine surfactants (alkyl betaine, amide betaine, sulfobetaine, etc.), and amphoteric surfactants such as acylmethyltaurine; sorbitan fatty acid esters (sorbitan) Monostearate, sorbitan sesquioleate, etc.), glycerin fatty acids (glyceryl monostearate, etc.), propylene glycol fatty acid esters (propylene glycol monostearate, etc.), hardened castor oil derivatives, glycerin alkyl ethers, POE sorbitan fatty acid esters (POE sorbitan monooleate, polyoxyethylene sorbitan monostearate, etc.), POE sorbite fatty acid esters (POE-sorbitol monolaurate, etc.), POE glycerin fatty acid ester Tells (POE-glycerol monoisostearate, etc.), POE fatty acid esters (polyethylene glycol monooleate, POE distearate, etc.), POE alkyl ethers (POE2-octyldodecyl ether, etc.), POE alkylphenyl ethers (POE nonylphenyl) Ethers, etc.), Pluronic types, POE / POP alkyl ethers (POE / POP2-decyltetradecyl ether, etc.), Tetronics, POE castor oil / hardened castor oil derivatives (POE castor oil, POE hardened castor oil, etc.), Nonionic surfactants such as sucrose fatty acid esters and alkyl glucosides; moisturizing ingredients such as sodium pyrrolidonecarboxylate, lactic acid and sodium lactate; surface-treated mica, talc, kaolin, synthetic mica, Powders such as calcium oxide, magnesium carbonate, anhydrous silicic acid (silica), aluminum oxide, barium sulfate; surface may be treated, bengara, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, bitumen Inorganic pigments such as titanium oxide and zinc oxide; surfaces may be treated; pearling agents such as titanium mica, fish phosphorus foil, bismuth oxychloride; red 202 which may be laked , Red 228, Red 226, Yellow 4, Blue 404, Yellow 5, Red 505, Red 230, Red 223, Orange 201, Red 213, Yellow 204, Yellow 203, Blue Organic dyes such as No. 1, Green No. 201, Purple No. 201, Red No. 204; Organic powders such as polyethylene powder, polymethyl methacrylate, nylon powder, organopolysiloxane elastomer; Paraaminobenzoic acid UV absorbers; Anthranilic acid UV absorbers; Salicylic acid UV absorbers; Cinnamic acid UV absorbers; Benzophenone UV absorbers; Sugar UV absorbers; 2- (2'-hydroxy-5 ' UV absorbers such as -t-octylphenyl) benzotriazole and 4-methoxy-4'-t-butyldibenzoylmethane; lower alcohols such as ethanol and isopropanol; vitamin A or a derivative thereof, vitamin B6 hydrochloride, Vitamin B6 tripalmitate, vitamin B6 dioctanoate, vitamin B2 or derivatives thereof, vitamin B such as vitamin B12, vitamin B15 or derivatives thereof; vitamin E such as α-tocopherol, β-tocopherol, γ-tocopherol, vitamin E acetate , Vitamin D, vitamin H, Preferred examples include vitamins such as pantothenic acid, pantethine, pyrroloquinoline quinone, etc .; antibacterial agents such as phenoxyethanol; and organically modified clay minerals such as hectorite and dimethyl distearyl ammonium modified hectorite.

  The skin external preparation of the present invention is not particularly limited as long as it is a dosage form used in the cosmetic field, and a lotion preparation, an oil-in-water emulsion preparation, a water-in-oil emulsion preparation, a composite emulsion emulsion preparation, etc. are preferable examples. I can do it. The emulsifier form may be either a water-in-oil emulsifier form or an oil-in-water emulsifier form, but the water-in-oil emulsifier form is particularly preferred. Here, the water-in-oil emulsifier form is a term collectively referred to as an emulsifier form having an oil phase in the outer phase, and may contain an aqueous phase in the inner phase or may have an emulsion such as an oil-in-water emulsion. You may do it.

  The skin external preparation of the present invention includes 1) a compound represented by the above general formula (1), an optical isomer thereof and / or a pharmacologically acceptable salt thereof, and 2) a component having an anti-inflammatory action. By containing, it exhibits excellent “pigmentation prevention or improvement action (whitening action)”. In addition, when anti-wrinkle formation on skin is prevented or ameliorated, rough skin is prevented or improved, moisturizing action, acne and other preventive or ameliorating action, etc. Since the effect of the present invention is utilized when the above-described effect of preventing or improving pigmentation is exhibited, it belongs to the technical scope of the present invention.

  The external preparation for skin of the present invention can be produced by treating the above-mentioned optional components and essential components according to a conventional method.

Hereinafter, the present invention will be described in more detail with reference to examples.

<Manufacture example 5: Manufacturing method 1 of the skin external preparation of this invention>
According to the formulations shown in Table 1 and Table 2 below, external preparations for skin of the present invention (cosmetics: lotions 1 to 4) were prepared. That is, the prescription ingredients were heated to 80 ° C., stirred, dissolved, stirred and cooled, and then cosmetics (lotions 1 to 4) were obtained. Similarly, in the prescription ingredients of Table 1, “Compound represented by the general formula (1) of the present invention” was replaced with “Water”, Comparative Example 1, “Ingredient having anti-inflammatory action of the present invention” Comparative Example 2 substituted with “water”, and “Comparative Example 3 substituted with“ water ”for both“ the compound represented by the general formula (1) of the present invention ”and“ the component having anti-inflammatory action of the present invention ”were prepared. did. In addition, the content change in the external preparation for skin (cosmetics) of “the compound represented by the general formula (1) of the present invention” and “the component having anti-inflammatory action of the present invention” is the content of “water”. Was adjusted to 100% by mass as a whole.

<Test Example 1: Evaluation 1 of pigmentation inhibitory action of external preparation for skin of the present invention>
With respect to the external preparation for skin of the present invention (cosmetics: lotions 1 to 4) and Comparative Examples 1 to 3 produced according to the method described in Example 1, the pigmentation inhibitory action was evaluated according to the following procedure. A test site of 1.5 cm × 1.5 cm was provided on the first day (1st day) on the back of the panel that participated voluntarily, and the skin lightness (L * value) of the test site was measured using a color difference meter (CR-300 , Konica Minolta Co., Ltd.). After the skin brightness was measured on the first day of the test, the test site was irradiated with ultraviolet rays twice the minimum erythema amount (2 MED) once. 50 μL of each specimen (the lotions 1 to 4 or the cosmetics of Comparative Examples 1 to 3) was applied to each test site three times a day for 14 consecutive days immediately after the end of ultraviolet irradiation. 24 hours after the application (15th day), the skin lightness (L * value) of each test site was measured with a color difference meter (CR-300, Konica Minolta Co., Ltd.). ΔL * value for was calculated. The results are shown in Table 3. Since the L * value decreases as the degree of pigmentation increases, it can be determined that pigmentation is suppressed as the ΔL * value decreases (the absolute value of the ΔL * value). Thereby, it turns out that the skin external preparation (lotions 1-4) of this invention has the outstanding pigmentation inhibitory effect. Moreover, although the pigmentation inhibitory action was recognized also in the comparative example 1 and the comparative example 2, the effect was weak compared with cosmetics 1-4. Thereby, it turns out that the cosmetics 1-4 which are the skin external preparations of this invention show the outstanding pigmentation inhibitory effect.

<Production Example 6: Method 2 for producing skin external preparation of the present invention>
Table 4 shows “the compound represented by the general formula (1) of the present invention” and “the component having the anti-inflammatory action of the present invention” among the formulation components of the cosmetic (Lotion 1) described in Example 1. Cosmetics (Lotions 5 and 6) that were changed to the prescription ingredients were prepared.

<Test Example 2: Evaluation 2 of pigmentation inhibitory effect in humans of the external preparation for skin of the present invention>
Using the cosmetics (Lotions 5 and 6) of the present invention prepared according to the method described in Example 3 and Comparative Example 3, the pigmentation inhibitory effect was evaluated according to the test method described in Example 2. The results are shown in Table 5. It can be seen that the cosmetics (Lotions 5 and 6) of the present invention have a small ΔL * value as compared with Comparative Example 3, and show an excellent preventive or improving effect on pigmentation.

Skin external preparation of the present invention, that is, skin containing the compound represented by the general formula (1), optical isomers thereof and / or pharmacologically acceptable salts thereof, and a component having an anti-inflammatory action The external preparation exhibits an excellent effect of preventing or improving pigmentation.

  The present invention can be applied to cosmetics (however, including quasi drugs).

Claims (12)

A skin external preparation containing a compound represented by the following general formula (1), an optical isomer thereof and / or a pharmacologically acceptable salt thereof, and 2) a component having an anti-inflammatory action.

(1)
[Wherein, R ₁ represents an unsubstituted or substituted aromatic group, R ₂ represents a hydrogen atom, a linear or branched alkyl group having 1 to 4 carbon atoms, or a linear chain having 1 to 4 carbon atoms. Alternatively, it represents an acyl group having a branched alkyl chain, and R ₃ represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms. ] The compound represented by the general formula (1) is a compound represented by the following general formula (2), an optical isomer thereof and / or a pharmaceutically acceptable salt thereof. Topical skin preparation.

(2)
[Wherein, R ₄ represents an unsubstituted or substituted aromatic group, R ₅ represents a hydrogen atom, a linear or branched alkyl group having 1 to 4 carbon atoms, or a linear chain having 1 to 4 carbon atoms. Alternatively, it represents an acyl group having a branched alkyl chain. ] The compound represented by the general formula (1) is a compound represented by the following general formula (3), an optical isomer thereof, and / or a pharmaceutically acceptable salt thereof. Topical skin preparation.

(3)
[Wherein R ₆ represents an unsubstituted or substituted aromatic group, and R ₇ represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms. ] The compound represented by the general formula (1) is a compound represented by the following general formula (4), an optical isomer thereof and / or a pharmaceutically acceptable salt thereof. Topical skin preparation.

(4)
[Wherein R ₈ represents an unsubstituted or substituted aromatic group. ] The compound represented by the general formula (1) is N- (p-methylbenzoyl) serine (compound 1), N- (p-ethylbenzoyl) serine (compound 2), N- (p-methoxybenzoyl) serine. (Compound 3), N- (p-fluorobenzoyl) serine (Compound 4), N- (p-trifluoromethylbenzoyl) serine (Compound 5), N- (2-naphthoyl) serine (Compound 6), N- (4-phenylbenzoyl) serine (compound 7), N- (benzoyl) serine (compound 8), N- (p-methylbenzoyl) serine methyl ester (compound 9), N- (2-naphthoyl) serine methyl ester ( Compound 10), N-benzoyl-O-methylserine (compound 11), N- (p-methylbenzoyl) -O-methylserine (compound 12), N- (p-methylbenzoyl) -O-acetylse The skin external application according to claim 1, which is phosphorus (compound 13), N- (2-naphthoyl) -O-methylserine (compound 14), an optical isomer thereof and / or a pharmacologically acceptable salt thereof. Agent.

N- (p-methylbenzoyl) serine (Compound 1)

N- (p-ethylbenzoyl) serine (compound 2)

N- (p-methoxybenzoyl) serine (compound 3)

N- (p-fluorobenzoyl) serine (compound 4)

N- (p-trifluoromethylbenzoyl) serine (compound 5)

N- (2-naphthoyl) serine (Compound 6)

N- (4-Phenylbenzoyl) serine (Compound 7)

N- (benzoyl) serine (compound 8)

N- (p-methylbenzoyl) serine methyl ester (compound 9)

N- (2-naphthoyl) serine methyl ester (compound 10)

N-benzoyl-O-methylserine (compound 11)

N- (p-methylbenzoyl) -O-methylserine (compound 12)

N- (p-methylbenzoyl) -O-acetylserine (compound 13)

N- (2-naphthoyl) -O-methylserine (Compound 14) The compound represented by the general formula (1), optical isomers thereof and / or pharmacologically acceptable salts thereof are contained in an amount of 0.001% by mass to 10% by mass based on the total amount of the external preparation for skin. The skin external preparation as described in any one of claim | item 1 -5. The component having an anti-inflammatory action is a plant extract obtained from a plant belonging to the genus Camellia genus, a plant extract obtained from a plant belonging to the genus Asteraceae, a plant extract obtained from a plant belonging to the genus Clara , A plant extract obtained from a plant belonging to the genus Birchaceae, a plant extract obtained from a plant belonging to the family Walnut, a plant extract obtained from a plant belonging to the genus Leguminosae, a glycyrrhetinic acid derivative and / or a salt thereof, The skin external preparation as described in any one of Claims 1-6 which is 1 type (s) or 2 or more types selected from a glabrizine derivative and / or its salt. A plant belonging to the genus Camellia belonging to the family Asteraceae, a plant belonging to the genus Asteraceae, a plant belonging to the genus Clara, a plant belonging to the genus Birch, a plant belonging to the walnut family, a plant belonging to the genus Leguminosae, The topical skin preparation according to claim 7, which is a chamomile chamomile (chamomile), asteraceae burdock burdock, legume clara kujin, birch family birch birch, walnut koji, leguminous licorice. The said glycyrrhetic acid derivative is 1 type (s) or 2 or more types selected from glycyrrhetic acid and its salt, glycyrrhetinic acid alkyl and its salt, glycyrrhizic acid and its salt as described in any one of Claims 1-8. Skin external preparation. The skin external preparation as described in any one of Claims 1-9 which contains 0.00001 mass%-15 mass% of the component which has the said anti-inflammatory action with respect to skin external preparation whole quantity. The skin external preparation as described in any one of Claims 1-10 which is cosmetics (however, including a quasi-drug). The skin external preparation according to any one of claims 1 to 11, which is used for preventing or improving pigmentation.