JP2011241164A - Composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composition that exhibits an enhanced skin-beautifying action and is suitable, for example, for pharmaceuticals, cosmetics, foods, drinks and the like.SOLUTION: The composition contains (1) a compound represented by general formula, an isomer thereof and/or a pharmacologically acceptable salt thereof and (2) a skin-beautifying component. In the formula, Ris a hydrogen atom or a 1-8C linear or branched alkyl group; Ris a hydrogen atom, an unsubstituted or substituted aromatic group, or a 1-4C aliphatic hydrocarbon group substituted with an unsubstituted or substituted aromatic group; Ris an unsubstituted or substituted aromatic group; n is an integer of 1 or 2; and m is an integer of 0-3.

Description

  The present invention relates to a composition suitable for cosmetics (including quasi-drugs), foods, and the like. Specifically, 1) a compound represented by the following general formula (1), its isomers and / or them And 2) a whitening component, and a composition.

（１）
[式中、Ｒ１は、水素原子、炭素数１〜８の直鎖又は分岐のアルキル基を表し、Ｒ２は、水素原子、無置換又は置換基を有する芳香族基、無置換又は置換基を有する芳香族基により置換された炭素数１〜４の脂肪族炭化水素基を表し、Ｒ３は、無置換又は置換基を有する芳香族基を表し、ｎは、１又は２の整数、mは、０〜３の整数を表す。]

(1)
[Wherein, R1 represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, and R2 has a hydrogen atom, an aromatic group having no substituent or a substituent, an unsubstituted group or a substituent. Represents an aliphatic hydrocarbon group having 1 to 4 carbon atoms substituted by an aromatic group, R3 represents an unsubstituted or substituted aromatic group, n represents an integer of 1 or 2, and m represents 0. Represents an integer of ~ 3. ]

  Skin aging phenomena such as wrinkles, stains and sagging become apparent with aging due to genetic factors in addition to accumulation of physical stimuli such as temperature changes, ultraviolet rays and chemical exposure over many years. Such a skin aging phenomenon greatly affects the appearance of others, so it is an important concern for people to keep the beauty of the skin beautiful. Among the skin aging phenomena described above, it has been clarified that skin symptoms such as spots, freckles, and pigmentation after sunburn are caused by melanin production significantly increased by activation of pigment cells (melanocytes) present in the skin. ing. In addition, melanin overproduction in melanocytes is excessively transported to keratinocytes (keratinocytes) in addition to normal pigmentation symptoms, inactivating keratinocytes due to accumulation and discharge delay, etc., and worsening skin symptoms such as delamination cause. As described above, since melanin enhancement is deeply involved in skin phenomena caused by various pigmentation, various active ingredients including whitening agents are used to prevent or improve the deterioration of skin symptoms including abnormal pigmentation. R & D has been done. Examples of whitening agents found by such studies include ascorbic acid, hydrogen peroxide, colloidal sulfur, glutathione, hydroquinone, and catechols, and skin external preparations containing these as active ingredients are also known. Widely used (for example, see Non-Patent Document 1 and Non-Patent Document 2). Moreover, the mechanism of action of the whitening agents created up to now is wide-ranging, including melanin production inhibitors (for example, see Patent Document 1), tyrosinase enzyme inhibitors (for example, see Patent Document 2), A tyrosinase enzyme gene expression inhibitor, an α-MSH inhibitor (see, for example, Patent Document 3), an antioxidant and the like have been reported.

Moreover, aiming at a composition having a high whitening effect, in addition to the creation of a novel whitening active ingredient (for example, see Patent Document 4), a combination of a plurality of whitening active ingredients (for example, see Patent Document 5), Studies that enhance skin permeability or storage properties (for example, see Patent Document 6) by combining with specific prescription ingredients have been attempted. However, a certain whitening effect is recognized in attempts to enhance the whitening effect by combining a plurality of whitening components, and further, a combination of a whitening component and a specific prescription component, but until a satisfactory whitening effect is obtained. Has not reached. Furthermore, some external preparations for skin containing the above-mentioned whitening components have problems in stability and safety. On the other hand, as a result of extensive research on the whitening ingredients so far, material resources such as natural products or synthetic compounds have been extensively investigated, and the creation of new active ingredients has become difficult year by year. Attention has been focused more than ever on techniques for effectively exerting the whitening action of ingredients. In addition, although the above-mentioned whitening agent is expected to be effective for pigmentation abnormality due to normal melanin production, pigmentation abnormality accompanied by rough skin symptoms caused by excessive accumulation of melanin and delayed discharge in keratinocytes (keratinocytes), Or, there is almost no effect on pigmentation abnormalities such as incurable spots and dullness, and there has been a demand for the development of means for improving the darkness that exhibits such skin symptoms.

Various biological activities are known for 20 kinds of α-amino acids having different side chains including essential amino acids constituting a living body. Among the aforementioned α-amino acids, methionine, cysteine, and derivatives thereof are expected to have characteristic biological activities different from other α-amino acids due to the presence of a sulfur atom in the chemical structure, Attention has been paid. In fact, an acylated derivative of methionine is known to have an antioxidant effect (see, for example, Patent Document 7), and a dipeptide containing methionine has a whitening effect (see, for example, Patent Document 8). In addition, cysteic acid in which the sulfur atom of cysteine is oxidized and homocysteic acid, which is a derivative of cysteine, are attracting attention as metabolites in the living body. (See, for example, Patent Document 9). Furthermore, as for cysteic acid and homocysteic acid derivatives, skin peeling or epidermal renewal action on derivatives having a hydrogen atom, linear or branched alkyl or alkenyl group on the nitrogen atom (see, for example, Patent Document 10) Etc. are known. However, regarding compounds in which the nitrogen atom of cysteic acid and homocysteic acid is substituted by an aliphatic hydrocarbon group having an aromatic group, since the compound itself is a novel compound, its biological activity and structure-activity relationship are completely known. Not. In general, when organic compounds containing sulfur atoms in the molecular structure are applied to cosmetics, it is known that there are problems with the generation of off-flavors due to impurities and decomposition products, safety, and stability. ing. On the other hand, the compound represented by the general formula (1) can be stably blended in the composition together with the existing whitening component, and is excellent in the action of effectively enhancing the whitening action. Further, the compound represented by the general formula (1) has no off-flavor due to decomposition or the like even when blended in a composition such as a skin external preparation, and is soluble in a medium used for formulation, particularly a water-soluble medium. It is extremely good and is very stable in the compound and formulation form, so that it has excellent versatility for cosmetics and the like.

JP 2008-208073 A JP 2009-196895 A JP 2001-220347 A JP 2009-263258 A JP 2004-352630 A JP 2007-332115 A JP 2006-052152 A Japanese Patent Laid-Open No. 1993-032533 JP 2006-143649 A JP 09-110627 A

Supervised by Katsuyuki Takeda et al., “Usefulness of cosmetics, evaluation technology and future prospects”, published by Yakuji Nippo (2001). Noriyuki Omori, FRAGRANCE JOURNAL Special Issue, No. 14, 1995, 118-126.

  The present invention has been made under such circumstances, abnormal pigmentation due to ultraviolet exposure, especially, abnormal pigmentation due to increased melanin production, more specifically, the amount of melanin present in the collected horny layer cells. It is an object of the present invention to provide a composition such as an external preparation for skin, which is suitable for people who have a large amount of skin.

In view of such a situation, the present inventors, for the prevention or improvement of pigmentation abnormality due to UV exposure, further suitable for the prevention or improvement of pigmentation abnormality due to increased melanin production, etc. And 1) a compound represented by the following general formula (1), an isomer thereof and / or a pharmacologically acceptable salt thereof, and 2) a whitening component. The present invention has been completed by finding that such a characteristic is provided in a composition containing a bismuth. That is, the present invention is as follows.
<1> 1) A composition comprising a compound represented by the following general formula (1), an isomer thereof and / or a pharmacologically acceptable salt thereof, and 2) a whitening component. .

（１）
[式中、Ｒ１は、水素原子、炭素数１〜８の直鎖又は分岐のアルキル基を表し、Ｒ２は、水素原子、無置換又は置換基を有する芳香族基、無置換又は置換基を有する芳香族基により置換された炭素数１〜４の脂肪族炭化水素基を表し、Ｒ３は、無置換又は置換基を有する芳香族基を表し、ｎは、１又は２の整数、mは、０〜３の整数を表す。]

(1)
[Wherein, R1 represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, and R2 has a hydrogen atom, an aromatic group having no substituent or a substituent, an unsubstituted group or a substituent. Represents an aliphatic hydrocarbon group having 1 to 4 carbon atoms substituted by an aromatic group, R3 represents an unsubstituted or substituted aromatic group, n represents an integer of 1 or 2, and m represents 0. Represents an integer of ~ 3. ]

<2> The compound represented by the general formula (1) is a compound represented by the following general formula (2), an isomer thereof and / or a pharmacologically acceptable salt thereof. The composition according to <1>.

（２）
[式中、Ｒ４は、水素原子、炭素数１〜８の直鎖又は分岐のアルキル基を表し、Ｒ５は、無置換又は置換基を有する芳香族基を表し、nは、１又は２の整数、mは、０〜３の整数を表す。]

(2)
[Wherein, R4 represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, R5 represents an unsubstituted or substituted aromatic group, and n is an integer of 1 or 2. , M represents an integer of 0 to 3. ]

<3> The compound represented by the general formula (2) is a compound represented by the following general formula (3), an isomer thereof and / or a pharmacologically acceptable salt thereof. The composition according to <1> or <2>.

（３）
[式中、Ｒ６は、水素原子、炭素数１〜８の直鎖又は分岐のアルキル基を表し、Ｒ７は、無置換又は置換基を有する芳香族基を表し、nは、１又は２の整数を表す。]

(3)
[Wherein, R6 represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, R7 represents an unsubstituted or substituted aromatic group, and n is an integer of 1 or 2. Represents. ]

<4> The compound represented by the general formula (3) is a compound represented by the following general formula (4), an isomer thereof and / or a pharmacologically acceptable salt thereof. The composition according to any one of <1> to <3>.

（４）
[式中、Ｒ８は、水素原子、炭素数１〜８の直鎖又は分岐のアルキル基を表し、Ｒ９は、無置換又は置換基を有する芳香族基を表す。]

(4)
[Wherein, R8 represents a hydrogen atom or a linear or branched alkyl group having 1 to 8 carbon atoms, and R9 represents an unsubstituted or substituted aromatic group. ]

<5> The compounds represented by the general formulas (1) to (4) are N- (o-toluyl) cysteic acid (compound 1), N- (m-toluyl) cysteic acid (compound 2), N- (P-toluyl) cysteic acid (compound 3), N- (p-methoxybenzoyl) cysteic acid (compound 4), (N-biphenylcarbonyl) cysteic acid (compound 5), N- (p-toluyl) homocysteic acid <Compound 6>, isomers thereof and / or pharmacologically acceptable salts thereof, The composition according to any one of <1> to <4>.

N−（o−トルイル）システイン酸（化合物１）

N- (o-Toluyl) cysteic acid (Compound 1)

N−（m−トルイル）システイン酸（化合物２）

N- (m-Toluyl) cysteic acid (Compound 2)

N−（p−トルイル）システイン酸（化合物３）

N- (p-Toluyl) cysteic acid (Compound 3)

N−（p−メトキシベンゾイル）システイン酸（化合物４）

N- (p-methoxybenzoyl) cysteic acid (compound 4)

（N−ビフェニルカルボニル）システイン酸（化合物５）

(N-biphenylcarbonyl) cysteic acid (Compound 5)

N−（p−トルイル）ホモシステイン酸（化合物６）

N- (p-Toluyl) homocysteic acid (Compound 6)

<6> The compound represented by the general formula (1), its isomer and / or pharmacologically acceptable salt thereof is contained in an amount of 0.0001% by mass to 20% by mass with respect to the total amount of the composition. The composition according to any one of <1> to <5>, wherein
<7> The whitening component contains one or more selected from the group consisting of a melanin production inhibitor, an α-MSH inhibitor, a melanocyte dendriide elongation inhibitor, and a proton pump inhibitor. The composition according to any one of <1> to <6>.
<8> One selected from the group consisting of the melanin production inhibitor, α-MSH inhibitor, melanocyte dendrite elongation inhibitor, and proton pump inhibitor is any of the following: <1 > To <7>.
(Melanin production inhibitor): 4-alkylresorcinol and / or salt thereof, ascorbic acid derivative and / or salt thereof, hydroquinone and / or salt thereof, tranexamic acid derivative and / or salt thereof, Ursolic acid derivative and / or salt thereof, vitamin E and / or derivative thereof, pantethein-S-sulfonic acid and / or salt thereof (α-MSH inhibitor): plant extract obtained from legume Clara (Melanosite dendriide elongation inhibitor): Methyl ophiopogononone B, Sophoraflavanone A, Plant extract obtained from Asteraceae Achillea millefolium, Plant extract obtained from Liliaceae saccharum (proton pump inhibitor) Plant extract obtained from Musk genus Thyme, plant extract obtained from Clariaceae Clara , Plant extract obtained from ginger ginger genus ginger, plant extract obtained from taro family ginger genus ginger, plant extract obtained from cucurbitaceae genus gneiss, plant extract obtained from saxifragae hydrangea amacha, The plant extract obtained from the Sarcophagaceae matsuhodo fungus, the plant extract obtained from the leguminous genus Kihagi, the plant extract obtained from the leguminous genus Tokusahagi <9> The whitening component is based on the total amount of the composition It contains 0.000001 mass%-15 mass%, The composition as described in any one of <1>-<8> characterized by the above-mentioned.
<10> The composition according to any one of <1> to <9>, wherein the composition is a cosmetic (including a quasi-drug).
<11> The composition according to any one of <1> to <10>, wherein the composition is for whitening.
<12> The composition according to any one of <1> to <11>, which is used for prevention or improvement of pigmentation due to ultraviolet exposure.
<13> The composition according to <1> to <12>, which is used for prevention or improvement of pigmentation abnormality involving cell inactivation of keratinocytes caused by melanin overtransport.
<14> The composition according to any one of <1> to <13>, which is a skin external preparation.
<15> 1) A topical skin preparation comprising the compound represented by the general formula (1), an isomer thereof and / or a pharmacologically acceptable salt thereof, and 2) a whitening component. Agent.
<16> The compound represented by the general formula (1), its isomer and / or pharmacologically acceptable salt thereof is converted into the compound represented by the general formula (4), its isomer and / or Or it is a salt accept | permitted pharmacologically, The skin external preparation as described in <15> characterized by the above-mentioned.
<17> The compound represented by the general formula (1) is N- (o-toluyl) cysteic acid (compound 1), N- (m-toluyl) cysteic acid (compound 2), N- (p-toluyl). ) Cysteinic acid (compound 3), N- (p-methoxybenzoyl) cysteic acid (compound 4), (N-biphenylcarbonyl) cysteic acid (compound 5), N- (p-toluyl) homocysteic acid (compound 6) , An isomer thereof, and / or a pharmacologically acceptable salt thereof, The skin external preparation according to <15>.

N−（o−トルイル）システイン酸（化合物１）

N- (o-Toluyl) cysteic acid (Compound 1)

N−（m−トルイル）システイン酸（化合物２）

N- (m-Toluyl) cysteic acid (Compound 2)

N−（p−トルイル）システイン酸（化合物３）

N- (p-Toluyl) cysteic acid (Compound 3)

N−（p−メトキシベンゾイル）システイン酸（化合物４）

N- (p-methoxybenzoyl) cysteic acid (compound 4)

（N−ビフェニルカルボニル）システイン酸（化合物５）

(N-biphenylcarbonyl) cysteic acid (Compound 5)

N−（p−トルイル）ホモシステイン酸（化合物６）

N- (p-Toluyl) homocysteic acid (Compound 6)

<18> The whitening component contains one or more selected from the group consisting of a melanin production inhibitor, an α-MSH inhibitor, a melanocyte dendriide elongation inhibitor, and a proton pump inhibitor. The external preparation for skin according to any one of <15> to <17>.
<19> One selected from the group consisting of the melanin production inhibitor, the α-MSH inhibitor, the melanocyte dendrite elongation inhibitor, and the proton pump inhibitor is any one of the following: <15 The external preparation for skin according to any one of> to <18>.
(Melanin production inhibitor): 4-alkylresorcinol and / or salt thereof, ascorbic acid derivative and / or salt thereof, hydroquinone and / or salt thereof, tranexamic acid and / or derivative thereof, ursolic acid, Derivatives thereof and / or salts thereof, vitamin E and / or derivatives thereof, pantethein-S-sulfonic acid and / or salts thereof (α-MSH inhibitor): plant extracts obtained from the legume Clara genus Clara Dendride Elongation Inhibitor): Methyl ophiopogononone B, Sophoraflavanone A, Plant extract obtained from Asteraceae Achillea millefolium, Plant extract obtained from Liliaceae Aegypti (proton pump inhibitor): Lamiaceae Plant extract obtained from leguminous family Clara genus Clara, show Plant extract obtained from ginger family ginger, plant extract obtained from taro family ginger genus, plant extract obtained from cucurbitaceae ginkgo genus, plant extract obtained from saxifragae hydrangea amacha, sarnococcaceae matsuhod A plant extract obtained from Mycobacterium aeruginosa, a plant extract obtained from a leguminous genus Kihagi, a plant extract obtained from a leguminous genus Toxahahagi <20> characterized by being in a water-in-oil emulsifier form, < The external preparation for skin according to any one of 15> to <19>.
<21> The external preparation for skin according to any one of <15> to <20>, further comprising a preferable formulation component.

<The compound represented by the general formula (1) of the present invention, its isomer and / or pharmacologically acceptable salt thereof>
The composition of the present invention comprises 1) a compound represented by the general formula (1), an isomer thereof and / or a pharmacologically acceptable salt thereof, and 2) a whitening component. To do. The compound represented by the general formula (1) of the present invention, its isomer and / or pharmacologically acceptable salt thereof is a whitening component of the present invention described later, specifically, a melanin production inhibitor. , Α-MSH inhibitor, melanocyte dendrite elongation inhibitor, and one or two or more whitening components selected from the group consisting of proton pump inhibitors are included in the composition to enhance the whitening effect. To do. The whitening action in the present invention specifically refers to the prevention or improvement of pigmentation due to UV exposure, as well as the enhancement of melanin production in melanocytes by stimulating UV exposure, excessive transport of melanin to keratinocytes, accumulation and discharge delay, etc. It means the effect of preventing or improving pigmentation abnormalities such as abnormal skin pigmentation accompanied by rough skin such as delamination caused by cell inactivation of keratinocytes, irreparable stains, dullness and the like. The compound represented by the general formula (1), its isomer and / or pharmacologically acceptable salt thereof is a component that enhances the whitening effect by being contained in the composition together with the whitening component described later. If possible, it can be applied without any particular limitation, more preferably a component that enhances the prevention or improvement action of pigmentation abnormality caused by UV exposure, more preferably due to excessive production of melanin by stimulation such as UV exposure A component that enhances the effect of preventing or improving pigmentation can be suitably exemplified. In fact, in people with pigmentation abnormalities caused by UV exposure, excessive UV exposure causes melanin to be produced in the pigment cells (melanocytes) of the skin, and keratinization occurs due to excessive transport of melanin to keratinocytes (keratinocytes). Damages such as cell inactivation, turnover delay, etc. are given, and this is recognized as a rough skin phenomenon. In those who have abnormal pigmentation due to UV exposure, when the stratum corneum is prepared, the appearance rate of nucleated cells is higher than the average, and skin symptoms such as delamination of the skin are observed. Is done. Since the composition of the present invention is particularly preferably used for a person who exhibits the above-mentioned skin symptoms, symptoms due to observation of skin symptoms such as the appearance rate of nucleated cells by the preparation of a stratum corneum and skin delamination It is preferable to set a subject to be administered using as an index.

  Here, the compound represented by the general formula (1) will be described. In the formula, R1 represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, R2 represents a hydrogen atom, Represents an unsubstituted or substituted aromatic group, an unsubstituted or substituted aromatic group substituted with an aromatic group having 1 to 4 carbon atoms, and R3 represents an unsubstituted or substituted aromatic group Represents a group, n represents an integer of 1 or 2, and m represents an integer of 0 to 3. R1 represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, more preferably 1 to 4 carbon atoms, and specific examples include a hydrogen atom, a methyl group, an ethyl group, and propyl. A group, a butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, and the like can be preferably exemplified, and a hydrogen atom, a methyl group, and an ethyl group can be suitably exemplified. R2 represents a hydrogen atom, an unsubstituted or substituted aromatic group, or an unsubstituted or substituted aromatic group substituted with an aromatic group having 1 to 4 carbon atoms, and specific examples may be given. For example, hydrogen atom, phenyl group, methylphenyl group, ethylphenyl group, propylphenyl group, butylphenyl group, methoxyphenyl group, ethoxyphenyl group, propyloxyphenyl group, butyloxyphenyl group, hydroxyphenyl group, aminophenyl group, N-methylphenyl group, N-ethylphenyl group, N, N-dimethylaminophenyl group, N, N-diethylaminophenyl group, chlorophenyl group, bromophenyl group, fluorophenyl group, trifluoromethylphenyl group, pyridyl group, naphthyl Group, biphenyl group, benzyl group, methylbenzyl group, ethylbenzyl group, methoxy Cibenzyl group, ethoxybenzyl group, hydroxybenzyl group, aminobenzyl group, N-methylaminobenzyl group, N-ethylaminobenzyl group, chlorobenzyl group, fluorobenzyl group, trifluoromethylbenzyl group, naphthylmethyl group, biphenylmethyl group A phenylethyl group, a naphthylethyl group, a biphenylethyl group, a phenylpropyl group, a naphthylpropyl group, a biphenylpropyl group, a phenylbutyl group, a naphthylbutyl group, a biphenylbutyl group, and the like, more preferably a hydrogen atom, Preferred examples include a phenyl group and a benzyl group. R3 represents an unsubstituted or substituted aromatic group, and specific examples include a phenyl group, a methylphenyl group, an ethylphenyl group, a propylphenyl group, a butylphenyl group, a methoxyphenyl group, an ethoxyphenyl group, Propyloxyphenyl group, butyloxyphenyl group, hydroxyphenyl group, aminophenyl group, N-methylphenyl group, N-ethylphenyl group, N, N-dimethylaminophenyl group, N, N-diethylaminophenyl group, chlorophenyl group, Preferred examples include a bromophenyl group, a fluorophenyl group, a trifluoromethylphenyl group, a pyridyl group, a naphthyl group, and a biphenyl group, and more preferably a phenyl group, a methylphenyl group, a methoxyphenyl group, a naphthyl group, and a biphenyl group. It can illustrate suitably. The n represents an integer of 1 or 2, and more preferably, n = 1 can be suitably exemplified. The m represents an integer of 0 to 3, and more preferably m = 0. Among the compounds represented by the general formula (1), preferred are the compounds represented by the general formula (2), isomers thereof and / or pharmacologically acceptable salts thereof. More preferably, a compound represented by the general formula (3), an isomer thereof and / or a pharmacologically acceptable salt thereof can be preferably exemplified, and more preferably, the general formula (4) is exemplified. ), Its isomers and / or their pharmacologically acceptable salts. Specific examples of preferable compounds among the compounds represented by the general formula (1) include N-benzoylcysteic acid, N- (o-toluyl) cysteic acid (compound 1), N- (m -Toluyl) cysteic acid (compound 2), N- (p-toluyl) cysteic acid (compound 3), N- (p-methoxybenzoyl) cysteic acid (compound 4), (N-biphenylcarbonyl) cysteic acid (compound 5) ), N- (p-toluyl) homocysteic acid (Compound 6), its isomers and / or their pharmacologically acceptable salts. When such a compound is contained in the composition together with a whitening component to be described later, it exhibits an excellent effect of enhancing the preventive or improving action against pigmentation abnormality caused by exposure to ultraviolet rays. Further, such a compound is excellent in solubility in a medium used for formulation, in particular, in a polar medium, easily formulated into a skin external preparation, etc., and further excellent in stability and skin retention in the formulation, Excellent effect in preventing or improving pigmentation.

  Here, the compound represented by the general formula (2) will be described. In the formula, R4 represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, and R5 is unsubstituted or An aromatic group having a substituent is represented, n is an integer of 1 or 2, and m is an integer of 0 to 3. R4 represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, more preferably 1 to 4 carbon atoms, and specific examples include a hydrogen atom, a methyl group, an ethyl group, and a propyl group. A butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group and the like can be preferably exemplified, and a hydrogen atom, a methyl group and an ethyl group can be suitably exemplified. R5 represents an unsubstituted or substituted aromatic group. Specific examples include phenyl group, methylphenyl group, ethylphenyl group, propylphenyl group, butylphenyl group, methoxyphenyl group, ethoxyphenyl group, propyl group. Oxyphenyl group, butyloxyphenyl group, hydroxyphenyl group, aminophenyl group, N-methylphenyl group, N-ethylphenyl group, N, N-dimethylaminophenyl group, N, N-diethylaminophenyl group, chlorophenyl group, bromo A phenyl group, a fluorophenyl group, a trifluoromethylphenyl group, a pyridyl group, a naphthyl group, a biphenyl group and the like can be preferably exemplified, and more preferably, a hydrogen atom, a phenyl group and a benzyl group can be suitably exemplified. R5 represents an unsubstituted or substituted aromatic group, and specific examples include phenyl group, methylphenyl group, ethylphenyl group, propylphenyl group, butylphenyl group, methoxyphenyl group, ethoxyphenyl group, Propyloxyphenyl group, butyloxyphenyl group, hydroxyphenyl group, aminophenyl group, N-methylphenyl group, N-ethylphenyl group, N, N-dimethylaminophenyl group, N, N-diethylaminophenyl group, chlorophenyl group, Preferred examples include a bromophenyl group, a fluorophenyl group, a trifluoromethylphenyl group, a pyridyl group, a naphthyl group, and a biphenyl group, and more preferably a phenyl group, a methylphenyl group, a methoxyphenyl group, a naphthyl group, and a biphenyl group. It can illustrate suitably. The n represents an integer of 1 or 2, and more preferably, n = 1 can be suitably exemplified. The m represents an integer of 0 to 3, and more preferably m = 0. Specific examples of the compound represented by the general formula (2) that are not included in the compound represented by the general formula (3) or (4) include N- (benzylcarbonyl) cysteic acid. N- (methylbenzylcarbonyl) cysteic acid, N- (ethylbenzylcarbonyl) cysteic acid, N- (propylbenzylcarbonyl) cysteic acid, N- (butylbenzylcarbonyl) cysteic acid, N- (methoxybenzylcarbonyl) cysteic acid N- (ethoxybenzylcarbonyl) cysteic acid, N- (propyloxybezylcarbonyl) cysteic acid, N- (butyloxybenzylcarbonyl) cysteic acid, N- (hydroxybenzylcarbonyl) cysteic acid, N- (aminobenzylcarbonyl) ) Cysteinic acid, N- (N'-methylaminobenzylcarbonyl) ) Cysteic acid, N- (N′-ethylaminobenzylcarbonyl) cysteic acid, N- (N ′, N′-dimethylaminobenzylcarbonyl) cysteic acid, N- (N ′, N′-diethylaminobenzylcarbonyl) cysteic acid N- (chlorobenzylcarbonyl) cysteic acid, N- (fluorobenzylcarbonyl) cysteic acid, N- (difluorobenzylcarbonyl) cysteic acid, N- (trifluoromethylbenzylcarbonyl) cysteic acid, [N- (benzylcarbonyl) Cysteinic acid] ethyl ester, [N- (methylbenzylcarbonyl) cysteic acid] ethyl ester, [N- (ethylbenzylcarbonyl) cysteic acid] ethyl ester, [N- (propylbenzylcarbonyl) cysteic acid] ethyl ester, [N -(Butylbenzylcarbonyl) system Acid] ethyl ester, [N- (methoxybenzylcarbonyl) cysteic acid] ethyl ester, [N- (ethoxybenzylcarbonyl) cysteic acid] ethyl ester, [N- (propyloxybezylcarbonyl) cysteic acid] ethyl ester, [N- (butyloxybenzylcarbonyl) cysteic acid] ethyl ester, [N- (hydroxybenzylcarbonyl) cysteic acid] ethyl ester, [N- (aminobenzylcarbonyl) cysteic acid] ethyl ester, [N- (N′- Methylaminobenzylcarbonyl) cysteic acid] ethyl ester, [N- (N′-ethylaminobenzylcarbonyl) cysteic acid] ethyl ester, [N- (N ′, N′-dimethylaminobenzylcarbonyl) cysteic acid] ethyl ester, [N- (N ', N'-diethylaminobenzylcarbonyl ) Cysteinic acid] ethyl ester, [N- (chlorobenzylcarbonyl) cysteic acid] ethyl ester, [N- (fluorobenzylcarbonyl) cysteic acid] ethyl ester, [N- (difluorobenzylcarbonyl) cysteic acid] ethyl ester, [ N- (trifluoromethylbenzylcarbonyl) cysteic acid] ethyl ester, N- (benzylcarbonyl) homocysteic acid, N- (methylbenzylcarbonyl) homocysteic acid, N- (ethylbenzylcarbonyl) homocysteic acid, N- ( Propylbenzylcarbonyl) homocysteic acid, N- (butylbenzylcarbonyl) homocysteic acid, N- (methoxybenzylcarbonyl) homocysteic acid, N- (ethoxybenzylcarbonyl) homocysteic acid, N- (propyloxybezylcarbonyl) Mocysteic acid, N- (butyloxybenzylcarbonyl) homocysteic acid, N- (hydroxybenzylcarbonyl) homocysteic acid, N- (aminobenzylcarbonyl) homocysteic acid, N- (N′-methylaminobenzylcarbonyl) homo Cysteinic acid, N- (N′-ethylaminobenzylcarbonyl) homocysteic acid, N- (N ′, N′-dimethylaminobenzylcarbonyl) homocysteic acid, N- (N ′, N′-diethylaminobenzylcarbonyl) homo Cysteic acid, N- (chlorobenzylcarbonyl) homocysteic acid, N- (fluorobenzylcarbonyl) homocysteic acid, N- (difluorobenzylcarbonyl) homocysteic acid, N- (trifluoromethylbenzylcarbonyl) homocysteic acid, [ N- (benzylcarbonyl) homo [Stayic acid] ethyl ester, [N- (methylbenzylcarbonyl) homocysteine acid] ethyl ester, [N- (ethylbenzylcarbonyl) homocysteine acid] ethyl ester, [N- (propylbenzylcarbonyl) homocysteine acid] ethyl ester , [N- (butylbenzylcarbonyl) homocysteine acid] ethyl ester, [N- (methoxybenzylcarbonyl) homocysteine acid] ethyl ester, [N- (ethoxybenzylcarbonyl) homocysteine acid] ethyl ester, [N- ( Propyloxybezylcarbonyl) homocysteic acid] ethyl ester, [N- (butyloxybenzylcarbonyl) homocysteic acid] ethyl ester, [N- (hydroxybenzylcarbonyl) homocysteic acid] ethyl ester, [N- (aminobenzyl) Carbonyl) homosis Inic acid] ethyl ester, [N- (N′-methylaminobenzylcarbonyl) homocysteic acid] ethyl ester, [N- (N′-ethylaminobenzylcarbonyl) homocysteic acid] ethyl ester, [N- (N ′ , N′-dimethylaminobenzylcarbonyl) homocysteine acid] ethyl ester, [N- (N ′, N′-diethylaminobenzylcarbonyl) homocysteine acid] ethyl ester, [N- (chlorobenzylcarbonyl) homocysteine acid] ethyl Ester, [N- (fluorobenzylcarbonyl) homocysteic acid] ethyl ester, [N- (difluorobenzylcarbonyl) homocysteine acid] ethyl ester, [N- (trifluoromethylbenzylcarbonyl) homocysteine acid] ethyl ester, Isomers and / or their pharmacologically acceptable salts are preferred Illustration can be. Among the compounds represented by the general formula (2), preferred are N-benzoylcysteic acid, N- (o-toluyl) cysteic acid (compound 1), N- (m-toluyl) cysteic acid (compound 2), N- (p-toluyl) cysteic acid (compound 3), N- (p-methoxybenzoyl) cysteic acid (compound 4), (N-biphenylcarbonyl) cysteic acid (compound 5), N- (p- Toluyl) homocysteic acid (compound 6), isomers thereof and / or pharmacologically acceptable salts thereof can be suitably exemplified. When such a compound is contained in the composition together with a whitening component to be described later, it exhibits an excellent effect of enhancing the preventive or improving action against pigmentation abnormality caused by exposure to ultraviolet rays. Further, such a compound is excellent in solubility in a medium used for formulation, in particular, in a polar medium, easily formulated into a skin external preparation, etc., and further excellent in stability and skin retention in the formulation, Excellent effect in preventing or improving pigmentation.

Here, the compound represented by the general formula (3) will be described. In the formula, R6 represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, and R7 is unsubstituted or An aromatic group having a substituent is represented, and n represents an integer of 1 or 2. R6 represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, more preferably 1 to 4 carbon atoms, and specific examples include a hydrogen atom, a methyl group, an ethyl group, and a propyl group. A butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group and the like can be preferably exemplified, and a hydrogen atom, a methyl group and an ethyl group can be suitably exemplified. R7 represents an unsubstituted or substituted aromatic group, and specific examples include phenyl, methylphenyl, ethylphenyl, propylphenyl, butylphenyl, methoxyphenyl, ethoxyphenyl, and propyl. Oxyphenyl group, butyloxyphenyl group, hydroxyphenyl group, aminophenyl group, N-methylphenyl group, N-ethylphenyl group, N, N-dimethylaminophenyl group, N, N-diethylaminophenyl group, chlorophenyl group, bromo A phenyl group, a fluorophenyl group, a trifluoromethylphenyl group, a pyridyl group, a naphthyl group, a biphenyl group and the like can be preferably exemplified, and more preferably, a hydrogen atom, a phenyl group and a benzyl group can be suitably exemplified. R5 represents an unsubstituted or substituted aromatic group, and specific examples include phenyl group, methylphenyl group, ethylphenyl group, propylphenyl group, butylphenyl group, methoxyphenyl group, ethoxyphenyl group, Propyloxyphenyl group, butyloxyphenyl group, hydroxyphenyl group, aminophenyl group, N-methylphenyl group, N-ethylphenyl group, N, N-dimethylaminophenyl group, N, N-diethylaminophenyl group, chlorophenyl group, Preferred examples include a bromophenyl group, a fluorophenyl group, a trifluoromethylphenyl group, a pyridyl group, a naphthyl group, and a biphenyl group, and more preferably a phenyl group, a methylphenyl group, a methoxyphenyl group, a naphthyl group, and a biphenyl group. It can illustrate suitably. The n represents an integer of 1 or 2, and more preferably, n = 1 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) homocysteic acid, N- (methyl Benzoyl) homocysteic acid, N- (ethylbenzoyl) homocysteic acid, N- (propylbenzoyl) homocysteic acid, N- (butylbenzoyl) homocysteic acid, N- (methoxybenzoyl) homocysteic acid, N- (ethoxy Benzoyl) homocysteic acid, N- (propyloxybenzoyl) homocysteic acid, N- (butyloxybenzoyl) homocysteic acid, N- (hydroxybenzoyl) homocysteic acid, N- (aminobenzoyl) homocysteic acid, N- (N'-methylaminobenzoyl) homocysteic acid, N- (N'-ethylaminobenzoyl) homosis Inacid, N- (N ′, N′-dimethylaminobenzoyl) homocysteic acid, N- (N ′, N′-diethylaminobenzoyl) homocysteic acid, N- (chlorobenzoyl) homocysteic acid, N- (fluoro Benzoyl) homocysteic acid, N- (difluorobezoyl) homocysteic acid, N- (trifluoromethylbenzoyl) homocysteic acid, N- (naphthylcarbonyl) homocysteic acid, N- (biphenylcarbonyl) homocysteic acid, N -(Benzoyl) homocysteic acid methyl ester, N- (methylbenzoyl) homocysteic acid methyl ester, N- (ethylbenzoyl) homocysteic acid methyl ester, N- (propylbenzoyl) homocysteic acid methyl ester, N- (butyl Benzoyl) homocysteine acid methyl ester, N- ( Toxibenzoyl) homocysteine acid methyl ester, N- (ethoxybenzoyl) homocysteine acid methyl ester, N- (propyloxybenzoyl) homocysteine acid methyl ester, N- (butyloxybenzoyl) homocysteine acid methyl ester, N- ( Hydroxybenzoyl) homocysteic acid methyl ester, N- (aminobenzoyl) homocysteic acid methyl ester, N- (N'-methylaminobenzoyl) homocysteic acid methyl ester, N- (N'-ethylaminobenzoyl) homocysteic acid Methyl ester, N- (N ′, N′-dimethylaminobenzoyl) homocysteine acid methyl ester, N- (N ′, N′-diethylaminobenzoyl) homocysteine acid methyl ester, N- (chlorobenzoyl) homocysteine acid methyl ester Ter, N- (fluorobenzoyl) homocysteic acid methyl ester, N- (difluorobezoyl) homocysteic acid methyl ester, N- (trifluoromethylbenzoyl) homocysteic acid methyl ester, N- (naphthylcarbonyl) homocysteic acid Methyl ester, N- (biphenylcarbonyl) homocysteine acid methyl ester, N- (benzoyl) homocysteic acid ethyl ester, N- (methylbenzoyl) homocysteine acid ethyl ester, N- (ethylbenzoyl) homocysteine acid ethyl ester, N- (propylbenzoyl) homocysteine acid ethyl ester, N- (butylbenzoyl) homocysteine acid ethyl ester, N- (methoxybenzoyl) homocysteine acid ethyl ester, N- (ethoxybenzoyl) homocysteine Acid ethyl ester, N- (propyloxybenzoyl) homocysteine acid ethyl ester, N- (butyloxybenzoyl) homocysteine acid ethyl ester, N- (hydroxybenzoyl) homocysteine acid ethyl ester, N- (aminobenzoyl) homocysteine Acid ethyl ester, N- (N′-methylaminobenzoyl) homocysteine acid ethyl ester, N- (N′-ethylaminobenzoyl) homocysteine acid ethyl ester, N- (N ′, N′-dimethylaminobenzoyl) homo Cysteinic acid ethyl ester, N- (N ′, N′-diethylaminobenzoyl) homocysteic acid ethyl ester, N- (chlorobenzoyl) homocysteic acid ethyl ester, N- (fluorobenzoyl) homocysteic acid ethyl ester, N- ( Difluorobezoyl) Mocysteine acid ethyl ester, N- (trifluoromethylbenzoyl) homocysteine acid ethyl ester, N- (naphthylcarbonyl) homocysteine acid ethyl ester, N- (biphenylcarbonyl) homocysteine acid ethyl ester, its isomers and / or Those pharmacologically acceptable salts can be preferably exemplified. Among the compounds represented by the general formula (3), N-benzoylcysteic acid, N- (o-toluyl) cysteic acid (compound 1), N- (m-toluyl) cysteic acid (compounds) are preferable. 2), N- (p-toluyl) cysteic acid (compound 3), N- (p-methoxybenzoyl) cysteic acid (compound 4), (N-biphenylcarbonyl) cysteic acid (compound 5), N- (p- Toluyl) homocysteic acid (compound 6), isomers thereof and / or pharmacologically acceptable salts thereof can be suitably exemplified. When such a compound is contained in the composition together with a whitening component to be described later, it exhibits an excellent effect of enhancing the preventive or improving action against pigmentation abnormality caused by exposure to ultraviolet rays. Further, such a compound is excellent in solubility in a medium used for formulation, in particular, in a polar medium, easily formulated into a skin external preparation, etc., and further excellent in stability and skin retention in the formulation, Excellent effect in preventing or improving pigmentation.

  Here, the compound represented by the general formula (4) will be described. In the formula, R8 represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, and R9 is unsubstituted or An aromatic group having a substituent is represented. R8 represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, more preferably 1 to 4 carbon atoms, and specific examples include a hydrogen atom, a methyl group, an ethyl group, and a propyl group. A butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group and the like can be preferably exemplified, and a hydrogen atom, a methyl group and an ethyl group can be suitably exemplified. R9 represents an unsubstituted or substituted aromatic group, and specific examples include phenyl group, methylphenyl group, ethylphenyl group, propylphenyl group, butylphenyl group, methoxyphenyl group, ethoxyphenyl group, Propyloxyphenyl group, butyloxyphenyl group, hydroxyphenyl group, aminophenyl group, N-methylphenyl group, N-ethylphenyl group, N, N-dimethylaminophenyl group, N, N-diethylaminophenyl group, chlorophenyl group, A bromophenyl group, a fluorophenyl group, a trifluoromethylphenyl group, a pyridyl group, a naphthyl group, a biphenyl group and the like can be preferably exemplified, and a hydrogen atom, a phenyl group and a benzyl group can be suitably exemplified. Specific examples of preferable compounds among the compounds represented by the general formula (5) include N- (benzoyl) cysteic acid, N- (methylbenzoyl) cysteic acid, N- (ethylbenzoyl) cysteic acid, N- (propylbenzoyl) cysteic acid, N- (butylbenzoyl) cysteic acid, N- (methoxybenzoyl) cysteic acid, N- (ethoxybenzoyl) cysteic acid, N- (propyloxybenzoyl) cysteic acid, N- (butyl Oxybenzoyl) cysteic acid, N- (hydroxybenzoyl) cysteic acid, N- (aminobenzoyl) cysteic acid, N- (N′-methylaminobenzoyl) cysteic acid, N- (N′-ethylaminobenzoyl) cysteic acid, N- (N ′, N′-dimethylaminobenzoyl) cysteic acid, N- (N ′, N′-diethyla Nobenzoyl) cysteic acid, N- (chlorobenzoyl) cysteic acid, N- (fluorobenzoyl) cysteic acid, N- (difluorobezoyl) cysteic acid, N- (trifluoromethylbenzoyl) cysteic acid, N- (naphthylcarbonyl) ) Cysteic acid, N- (biphenylcarbonyl) cysteic acid, N- (benzoyl) cysteic acid methyl ester, N- (methylbenzoyl) cysteic acid methyl ester, N- (ethylbenzoyl) cysteic acid methyl ester, N- (propylbenzoyl) ) Cysteinic acid methyl ester, N- (butylbenzoyl) cysteic acid methyl ester, N- (methoxybenzoyl) cysteic acid methyl ester, N- (ethoxybenzoyl) cysteic acid methyl ester, N- (propyloxybenzoyl) cysteine Acid methyl ester, N- (butyloxybenzoyl) cysteic acid methyl ester, N- (hydroxybenzoyl) cysteic acid methyl ester, N- (aminobenzoyl) cysteic acid methyl ester, N- (N′-methylaminobenzoyl) cysteic acid Methyl ester, N- (N′-ethylaminobenzoyl) cysteic acid methyl ester, N- (N ′, N′-dimethylaminobenzoyl) cysteic acid methyl ester, N- (N ′, N′-diethylaminobenzoyl) cysteic acid Methyl ester, N- (chlorobenzoyl) cysteic acid methyl ester, N- (fluorobenzoyl) cysteic acid methyl ester, N- (difluorobezoyl) cysteic acid methyl ester, N- (trifluoromethylbenzoyl) cysteic acid methyl ester, N- (Naph L-carbonyl) cysteic acid methyl ester, N- (biphenylcarbonyl) cysteic acid methyl ester, N- (benzoyl) cysteic acid ethyl ester, N- (methylbenzoyl) cysteic acid ethyl ester, N- (ethylbenzoyl) cysteic acid ethyl ester N- (propylbenzoyl) cysteic acid ethyl ester, N- (butylbenzoyl) cysteic acid ethyl ester, N- (methoxybenzoyl) cysteic acid ethyl ester, N- (ethoxybenzoyl) cysteic acid ethyl ester, N- (propyloxy Benzoyl) cysteic acid ethyl ester, N- (butyloxybenzoyl) cysteic acid ethyl ester, N- (hydroxybenzoyl) cysteic acid ethyl ester, N- (aminobenzoyl) cysteic acid ethyl ester Ter, N- (N′-methylaminobenzoyl) cysteic acid ethyl ester, N- (N′-ethylaminobenzoyl) cysteic acid ethyl ester, N- (N ′, N′-dimethylaminobenzoyl) cysteic acid ethyl ester, N- (N ′, N′-diethylaminobenzoyl) cysteic acid ethyl ester, N- (chlorobenzoyl) cysteic acid ethyl ester, N- (fluorobenzoyl) cysteic acid ethyl ester, N- (difluorobezoyl) cysteic acid ethyl ester N- (trifluoromethylbenzoyl) cysteic acid ethyl ester, N- (naphthylcarbonyl) cysteic acid ethyl ester, N- (biphenylcarbonyl) cysteic acid ethyl ester, its isomers and / or their pharmacologically acceptable A suitable salt can be exemplified. Among the compounds represented by the general formula (4), preferred are N-benzoylcysteic acid, N- (o-toluyl) cysteic acid (compound 1), N- (m-toluyl) cysteic acid (compound 2), N- (p-toluyl) cysteic acid (compound 3), N- (p-methoxybenzoyl) cysteic acid (compound 4), (N-biphenylcarbonyl) cysteic acid (compound 5), its isomers and / or Alternatively, pharmacologically acceptable salts thereof can be preferably exemplified. Such a compound has an effect of enhancing the excellent pigmentation prevention or improvement action by being contained in the composition together with the whitening component described later. When such a compound is contained in the composition together with a whitening component to be described later, it exhibits an excellent effect of enhancing the preventive or improving action against pigmentation abnormality caused by exposure to ultraviolet rays. Further, such a compound is excellent in solubility in a medium used for formulation, in particular, in a polar medium, easily formulated into a skin external preparation, etc., and further excellent in stability and skin retention in the formulation, Excellent effect in preventing or improving pigmentation.

In addition, the compound represented by the general formula (1), its isomer and / or pharmacologically acceptable salt thereof, together with the whitening component described later, is contained in the composition, thereby providing an excellent whitening effect. It has a potentiating effect, especially an excellent enhancing effect on the prevention or improvement of pigmentation abnormalities caused by UV exposure. Such enhancement effect of preventing or improving pigmentation is caused by abnormal pigmentation between the compound represented by the general formula (1), its isomer and / or pharmacologically acceptable salt, and a whitening component. In addition to the preventive or improving action against the substance or in addition to the synergistic action, the action of improving the delivery efficiency of the active ingredient to the target site, and the whitening action of the compound represented by the general formula (1) it is conceivable that. In addition to the racemic compound (DL form), the compounds represented by the general formulas (1) to (4) include D and L isomers. These isomers, when included in the composition together with the whitening component described later, all exhibit an excellent enhancing effect on the prevention or improvement of pigmentation abnormality, but are safe for the living body and stable in the preparation. The L form can be suitably exemplified by the nature and the like.

  The compounds represented by the general formulas (1) to (4), isomers thereof and / or pharmacologically acceptable salts thereof are commercially available cysteic acid, homocysteic acid, and derivatives thereof. Can be produced by carrying out deprotection, coupling, and introduction of a protecting group according to the methods described in “Basics and Experiments of Peptide Synthesis (Maruzen)”, etc. It can also be produced by a method. When such a compound is contained in the composition together with a component having a whitening effect as described later, the effect of preventing or improving pigmentation due to UV exposure is enhanced, especially, due to excessive production of melanin due to stimulation such as UV exposure. It can also be used to enhance the effect of preventing or improving pigmentation, but it can also be treated with a pharmacologically acceptable acid or base, converted into a salt form, and used as a salt. For example, mineral salts such as hydrochloride, sulfate, nitrate, phosphate, carbonate, maleate, fumarate, oxalate, citrate, lactate, tartrate, methanesulfonate, para Organic acid salts such as toluene sulfonate and benzene sulfonate, alkali metals such as sodium salt and potassium salt, alkaline earth metals such as calcium salt and magnesium salt, triethylamine salt, triethanolamine salt, ammonium salt, monoethanol Preferred examples include organic amine salts such as ruamine salt and piperidine salt, and basic amino acid salts such as lysine salt and alginate.

  The compound represented by the general formula (1) of the present invention, its isomer and / or pharmacologically acceptable salt thereof works together with the whitening component described later, whitening action, particularly, pigmentation by exposure to ultraviolet rays. In order to exert an enhancing effect on the prevention or improvement of abnormalities, the total amount is 0.0001% by mass to 20% by mass, more preferably 0.001% by mass to 10% by mass, and still more preferably, with respect to the total amount of the composition. It is preferable to contain 0.01 mass%-5 mass%. This is because if the amount is too small, the above effect may not be achieved, and if the amount is too large, the effect may reach its peak and the degree of freedom of the system may be impaired.

N−（o−トルイル）−L−システイン酸（化合物１のL異性体）

N- (o-Toluyl) -L-cysteic acid (L isomer of Compound 1)

<Production Example 1: Synthesis of L isomer of Compound 1>
L-cysteic acid 3 (g) (17.7 mmol) (Tokyo Chemical Industry Co., Ltd.), tetrahydrofuran 18 (mL) (Wako Pure Chemical Industries, Ltd.) and water 18 (mL) are placed in a 100 (mL) eggplant-shaped flask. Then, it was cooled in an ice bath. After sufficiently cooling, 4.40 (g) (31.6 mmol) of potassium carbonate (Wako Pure Chemical Industries, Ltd.) was added. o-Toluoyl chloride 3.28 (g) (Tokyo Chemical Industry Co., Ltd.) was sequentially added so that the liquid temperature did not rise. After the addition, the ice bath was removed and the mixture was stirred at room temperature. After confirming the progress of the reaction by thin layer chromatography, tetrahydrofuran was distilled off under reduced pressure. The obtained residue was washed with ethyl acetate, and the pH was adjusted to 2 or less with hydrochloric acid. The filtrate was concentrated and water (20 ml) was added. The precipitated crystals were collected by filtration, and the crystals were washed with acetone. The crystal collected by filtration was dried at 60 ° C. to obtain 0.78 (g) (2,72 mmol) of the L isomer of Compound 1 having the above structure. Shown below are the values of the indications.
¹ H-NMR (D ₂ O): δ 2.31 (3H, s), 3.42 (2H, m), 4.86 (1H, m), 7.24 (2H, m), 7.35 (2H, m).
FAB-MS (negative ion mode): M / z = 286 ([M−H] ⁻ )

N−（m−トルイル）−Ｌ−システイン酸（化合物２のＬ異性体）

N- (m-Toluyl) -L-cysteic acid (L isomer of compound 2)

<Production Example 2: Synthesis of L isomer of Compound 2>
L-cysteic acid 3 (g) (17.7 mmol) (Tokyo Chemical Industry Co., Ltd.), tetrahydrofuran 18 (mL) (Wako Pure Chemical Industries, Ltd.), and water 18 (mL) in a 100 (mL) eggplant type flask And then cooled in an ice bath. After sufficiently cooling, the liquid temperature of potassium carbonate 4.40 (g) (31.6 mmol) (Wako Pure Chemical Industries, Ltd.), m-toluoyl chloride 2.19 (g) (Tokyo Chemical Industry Co., Ltd.) Sequentially added so as not to rise. After reacting in an ice bath for 1 hour, m-toluoyl chloride 1.09 (g) (Tokyo Chemical Industry Co., Ltd.) was added again. After the addition, the ice bath was removed and the mixture was stirred at room temperature. After confirming the progress of the reaction by thin layer chromatography, tetrahydrofuran was distilled off under reduced pressure. The obtained residue was washed with ethyl acetate, and the pH was adjusted to 2 or less with hydrochloric acid. The filtrate was concentrated and water (18 mL) was added. After aging at 4 ° C., the precipitated crystals were separated by filtration. The obtained crystals were washed with acetone and collected by filtration. The crystals collected by filtration were dried at 60 ° C. to obtain 1.65 (g) (5.74 mmol) of L isomer of compound 2 having the above structure. Shown below are the values of the indications.
¹ H-NMR (DMSO-d ₆ ): δ 2.36 (3H, s), 2.94 (2H, m), 4.41 (1H, m), 7.36 (2H, d), 7. 58 (2H, t), 8.84 (1H, d), 12.5 (1H, bs).
FAB-MS (negative ion mode): M / z = 286 ([M−H] ⁻ )

N−（p−トルイル）−Ｌ−システイン酸（化合物３のＬ異性体）

N- (p-Toluyl) -L-cysteic acid (L isomer of compound 3)

<Production Example 3: Synthesis of L isomer of Compound 3>
100 g of L-cysteic acid monohydrate 5 (g) (26.7 mmol) (Sigma Aldrich), 1,4-dioxane 20 (mL) (Wako Pure Chemical Industries, Ltd.), and water 10 (mL) (ML) After placing in an eggplant-shaped flask, it was cooled in an ice bath. After sufficiently cooling, 10.7 (mL) of 8 (N) sodium hydroxide aqueous solution and 3.36 (mL) of p-toluoyl chloride (Sigma Aldrich) were successively added dropwise so that the liquid temperature did not rise. After completion of dropping, the ice bath was removed and the mixture was stirred at room temperature. After confirming the progress of the reaction by thin layer chromatography, 1,4-dioxane was distilled off under reduced pressure. The obtained residue was washed with ethyl acetate, and the pH was adjusted to 2 or less with hydrochloric acid. The obtained aqueous solution was freeze-dried, and the target product was extracted with methanol. The methanol was distilled off under reduced pressure, crystallized and filtered. The crystal collected by filtration was dried to obtain 5.79 (g) (20.2 mmol) of L isomer of Compound 3 having the above structure. Indicative values are shown below.
¹ H-NMR (D ₂ O): δ 2.32 (3H, s), 3.46 (2H, m), 4.87 (1H, m), 7.25 (2H, d), 7.64 (2H, d).
FAB-MS (negative ion mode): M / z = 286 ([M−H] ⁻ ), 308 ([M + Na−H] ⁻ )

N−（p−メトキシベンゾイル）−Ｌ−システイン酸（化合物４のＬ異性体）

N- (p-methoxybenzoyl) -L-cysteic acid (L isomer of compound 4)

<Production Example 4: Synthesis of L isomer of compound 4>
L-cysteic acid 2 (g) (11.8 mmol) (Tokyo Chemical Industry Co., Ltd.), tetrahydrofuran 12 (mL) (Wako Pure Chemical Industries, Ltd.), and water 12 (mL) in 100 (mL) eggplant type flask And then cooled in an ice bath. After sufficiently cooling, the liquid temperature of potassium carbonate 2.94 (g) (21.3 mmol) (Wako Pure Chemical Industries, Ltd.), 4-methoxybenzoyl chloride 1.61 (g) (Tokyo Chemical Industry Co., Ltd.) Sequentially added so as not to rise. After reacting for 1 hour in an ice bath, 4-methoxybenzoyl chloride 0.81 (g) (Tokyo Chemical Industry Co., Ltd.) was added again. After the addition, the ice bath was removed and the mixture was stirred at room temperature. After confirming the progress of the reaction by thin layer chromatography, tetrahydrofuran was distilled off under reduced pressure. The obtained residue was washed with ethyl acetate, and the pH was adjusted to 2 or less with hydrochloric acid. The precipitated crystals were filtered and washed with water. The filtrate was concentrated and the precipitated crystals were filtered again. The obtained crystals were combined and then washed with acetone. After filtering the crystals, the collected crystals were dried at 60 ° C. to obtain L isomer 2.47 (g) (8.14 mmol) of Compound 4 having the above structure. Indicative values are shown below.
¹ H-NMR (D ₂ O): δ 3.45 (2H, m), 3.81 (3H, s), 4.85 (1H, m), 7.00 (2H, d), 7.72 (2H, d).
FAB-MS (negative ion mode): M / z = 302 ([M−H] ⁻ )

（Ｎ−ビフェニルカルボニル）−Ｌ−システイン酸（化合物５のＬ異性体）

(N-biphenylcarbonyl) -L-cysteic acid (L isomer of compound 5)

<Production Example 5: Synthesis of L isomer of compound 5>
L-cysteic acid 2 (g) (11.8 mmol) (Tokyo Chemical Industry Co., Ltd.), tetrahydrofuran 12 (mL) (Wako Pure Chemical Industries, Ltd.), and water 12 (mL) in 100 (mL) eggplant type flask And then cooled in an ice bath. After sufficiently cooling, the liquid temperature of potassium carbonate 2.94 (g) (21.3 mmol) (Wako Pure Chemical Industries, Ltd.), 4-phenylbenzoyl chloride 2.05 (g) (Tokyo Chemical Industry Co., Ltd.) Sequentially added so as not to rise. After reacting for 1.5 hours in an ice bath, 4-phenylbenzoyl chloride 1.02 (g) (Tokyo Chemical Industry Co., Ltd.) was added again. After the addition, the ice bath was removed and the mixture was stirred at room temperature. After confirming the progress of the reaction by thin layer chromatography, tetrahydrofuran was distilled off under reduced pressure. The obtained residue was washed with ethyl acetate, and the pH was adjusted to 2 or less with hydrochloric acid. The precipitated crystals were filtered and washed with water. The obtained crystals were washed with acetone and then filtered. The crystals collected by filtration were dried at 60 ° C. to obtain L isomer 2.37 (g) (6.78 mmol) of compound 5 having the above structure. Indicative values are shown below.
¹ H-NMR (DMSO-d ₆ ): δ 2.96 (2H, m), 4.54 (1H, q), 7.42 (1H, m), 7.51 (2H, m), 7. 74 (2H, d), 7.80 (2H, d), 7.90 (2H, d), 8.94 (1H, d).
FAB-MS (negative ion mode): M / z = 348 ([M−H] ⁻ )

N−（p−トルイル）ホモシステイン酸（化合物６）

N- (p-Toluyl) homocysteic acid (Compound 6)

<Production Example 6: Synthesis of Compound 6>
DL-homocysteic acid 2 (g) (10.9 mmol) (Sigma Aldrich), tetrahydrofuran 12 (mL) (Wako Pure Chemical Industries, Ltd.) and water 12 (mL) into a 100 (mL) eggplant type flask After putting, it was cooled in an ice bath. After sufficiently cooling, potassium carbonate 2.71 (g) (19.6 mmol) (Wako Pure Chemical Industries, Ltd.) was added. p-Toluoyl chloride 1.49 (g) (Sigma Aldrich) was sequentially added so that the liquid temperature did not increase. After reacting for 1 hour in an ice bath, p-toluoyl chloride 0.76 (g) (Sigma Aldrich) was added again. After the addition, the ice bath was removed and the mixture was stirred at room temperature. After confirming the progress of the reaction by thin layer chromatography, tetrahydrofuran was distilled off under reduced pressure. The obtained residue was washed with ethyl acetate, and the pH was adjusted to 2 or less with hydrochloric acid. After filtration of the solution, the filtrate was concentrated and methanol was added. The precipitated crystals were separated by filtration and washed with water. The crystals were filtered, and the collected crystals were dried at 60 ° C. to obtain compound 61.95 (g) (6.47 mmol) having the above structure. Indicative values are shown below.
¹ H-NMR (DMSO-d ₆ ): δ 2.12 (2H, m), 2.35 (3H, s), 2.57 (2H, t), 4.37 (1H, m), 7. 26 (2H, d), 7.79 (2H, d), 9.02 (1H, d).
FAB-MS (negative ion mode): M / z = 300 ([M−H] ⁻ )

<Whitening component which is an essential component of the composition of the present invention>
The composition of the present invention comprises 1) a compound represented by the general formula (1), an isomer thereof and / or a pharmacologically acceptable salt thereof, and 2) a whitening component. To do. The whitening component of the present invention can be applied without particular limitation as long as it has a whitening action, more preferably a melanin production inhibitor, an α-MSH inhibitor, a melanocyte dendrite elongation inhibitor, a proton pump. Inhibitors can be preferably exemplified. The whitening component of the present invention not only has a whitening effect in itself, but also in the composition together with the compound represented by the general formula (1), its isomer and / or pharmacologically acceptable salt thereof. By containing, it has the effect of enhancing the preventive or ameliorating action against abnormal pigmentation due to ultraviolet exposure, and in particular, the action of enhancing the preventive or improving action of pigmentation caused by excessive production of melanin by stimulation such as ultraviolet exposure. Suitable examples of the whitening component include simple chemical substances and plant-derived extracts containing the compound. Here, the plant-derived extract means a generic name of the plant extract itself, a fraction obtained by fractionating and purifying the plant extract, a plant extract or fraction, and a solvent-removed product of the purified product. When the whitening component is contained in the composition together with the compound represented by the general formula (1), its isomer and / or pharmacologically acceptable salt thereof, it is selected from the group consisting of the whitening component. It is possible to contain only one kind of whitening component, or two or more kinds may be contained in combination.

Among the whitening components in the present invention, the melanin production inhibitor will be described. The melanin production inhibitor of the present invention can be applied without particular limitation as long as it has a melanin production inhibitory action, and more preferably, for example, a melanin production inhibitory action test described in JP-A-2009-155236. In the above, a component exhibiting a melanin production inhibitory effect of 50% or more at a test substance addition concentration that does not exhibit cytotoxicity can be suitably exemplified. Specific examples of preferred melanin production inhibitors include 4-alkylresorcinol and / or their pharmacologically acceptable salts, ascorbic acid derivatives and / or their pharmacology. Pharmaceutically acceptable salts, hydroquinone derivatives and / or pharmacologically acceptable salts thereof, tranexamic acid derivatives and / or pharmacologically acceptable salts thereof, vitamin E, derivatives thereof and / or their Preferred examples include a pharmacologically acceptable salt, pantethein-S-sulfonic acid and / or a pharmacologically acceptable salt thereof. Other whitening components include 4-alkoxysalicylic acid such as 4-methoxysalicylic acid and / or pharmacologically acceptable salts thereof, 5,5′-dipropyl-biphenyl-2,2′-dio- Biphenyl derivatives such as ruthenium and / or their pharmacologically acceptable salts, nicotinic acid derivatives such as nicotinamide and / or their pharmacologically acceptable salts, unsaturated fatty acids such as linoleic acid And / or a pharmacologically acceptable salt thereof.

Among the melanin production inhibitors described above, 4-alkylresorcinol and / or pharmacologically acceptable salts thereof will be described. The 4-alkylresorcinol derivative of the present invention can be applied without particular limitation as long as it is a 4-alkylresorcinol having a melanin production inhibitory action and / or a pharmacologically acceptable salt thereof. More preferably, the 4-position alkyl group of 4-alkylresorcinol is a linear or branched alkyl group having 1 to 10 carbon atoms, more preferably 3 to 7 carbon atoms. The 4-alkylresorcinol having a linear or branched alkyl group and / or a pharmacologically acceptable salt thereof can be preferably exemplified. Specific examples of preferred 4-alkylresorcinol and / or pharmacologically acceptable salts thereof include 4-methylresorcinol, 4-ethylresorcinol, 4-propyl resorcinol. Solcinol, 4- (1-methylethyl) resorcinol, 4-n-butyl resorcinol, 4- (2-methylpropyl resorcinol), 4- (1-methylethyl resorcinol) 1) -ethylpropyl resorcinol, 1-ethyl-2-methylpropyl resorcinol, 1-isopropyl-2-methylpropyl resorcinol, 1-butylpentyl resorcinol 1-isopropyl-2-methylpropyl resorcinol, 1-butylpentyl resorcinol, 1-isobutyl-3-methylbutyl resorcinol, 4- (1-methylpropyl) ) Resorcinol, 4- (1-methylbutyl) resorcinol, 4-tert-butyl resorcinol and / or their pharmacologically acceptable salts, and the like, more preferably 4-n -Butyl resorcinol and / or a pharmacologically acceptable salt thereof can be preferably exemplified.

  The 4-alkylresorcinol and / or a pharmacologically acceptable salt thereof is a compound represented by the general formula (1), an isomer thereof and / or a pharmacologically acceptable salt thereof. In order to work together with the salt and enhance the effect of preventing or improving pigmentation abnormality, the compound is 0.0001% by mass to 5% by mass in total with respect to the total amount of the composition, more preferably, It is preferable to contain 0.001 mass%-3 mass%, More preferably, 0.01 mass%-2 mass%. This is because if the amount is too small, the above effect may not be achieved, and if the amount is too large, the effect may reach its peak and the degree of freedom of the system may be impaired.

The 4-alkylresorcinol is prepared by a method in which a carboxylic acid having a corresponding alkyl group and resorcin are condensed in the presence of zinc chloride and reduced with zinc amalgam / hydrochloric acid, or an alcohol having a corresponding alkyl group. -A known synthesis method such as a method of condensing ru and resorcin at a high temperature of 200 to 400 ° C (for example, Lille, J .; Bitter, LA; Peiner, V. Trudy-Nauchono- Issledovatel'skii Institut Slantsev (1969 No. 18, 127-134, Japanese Patent Application Laid-Open No. 2006-124358, Japanese Patent Application Laid-Open No. 2006-124357), or a commercially available reagent.

Among the melanin production inhibitors, ascorbic acid derivatives and / or pharmacologically acceptable salts thereof will be described. The ascorbic acid derivatives and their pharmacologically acceptable salts of the present invention are applicable without particular limitation as long as they are ascorbic acid derivatives having a melanin production inhibitory action and / or their pharmacologically acceptable salts. More preferably, water-soluble ascorbic acid derivatives and / or pharmacologically acceptable salts thereof can be preferably exemplified. Specific examples of the ascorbic acid derivatives and / or pharmacologically acceptable salts thereof include ascorbic acid, ascorbic acid phosphate, ascorbic acid-2-glycoside (simply referred to as ascorbic acid glucoside) And / or pharmacologically acceptable salts thereof can be suitably exemplified, and ascorbic acid, ascorbic acid-2-glucoside and / or pharmacologically acceptable salts thereof are more preferable. Can be illustrated.

  The ascorbic acid, derivative thereof and / or pharmacologically acceptable salt thereof is a compound represented by the general formula (1), isomer thereof and / or pharmacologically acceptable salt thereof. In order to work together with the enhancement effect on the prevention or improvement of pigmentation abnormality, the total amount is 0.1% by mass to 10% by mass, more preferably 0.5% by mass to 5% by mass with respect to the total amount of the composition. % Content is preferable. This is because if the amount is too small, the above effect may not be achieved, and if the amount is too large, the effect may reach its peak and the degree of freedom of the system may be impaired.

  Among the melanin production inhibitors, hydroquinone derivatives and / or pharmacologically acceptable salts thereof will be described. The hydroquinone derivatives and their pharmacologically acceptable salts of the present invention can be applied without particular limitation as long as they are hydroquinone derivatives having an inhibitory action on melanin production and their pharmacologically acceptable salt conductors. More preferably, a hydroquinone glycoside can be preferably exemplified. Examples of the sugar chain portion of the hydroquinone glycoside include L-arabinose, D-xylos, D-ribose, D-xylose, D-lyxose, D-ribose and the like. Pentose sugar, D-glucose, D-galactose, D-mannose, D-tagalose, D-fructose, L-sorbose, etc. Amino acid sugars such as D-galactosamine, sialic acid and muramic acid can be preferably exemplified. Furthermore, as uronic acid or its methyl compound and acetyl compound, uronic acids such as D-glucuronic acid, D-galacturonic acid, D-mannuronic acid, L-iduronic acid, or their methyl compounds and acetyl compounds can be preferably exemplified. . Among these compounds, arbutin having a chemical structure in which hydroquinone and glucose are combined and / or a pharmacologically acceptable salt thereof can be preferably exemplified.

  The hydroquinone derivative can be obtained by a conventional method from hydroquinone and a corresponding sugar. For example, arbutin can be synthesized in a solution composed of hydroquinone and glucose by an enzymatic reaction using β-glucosidase (for example, JP-A No. 05-176785).

  The hydroquinone derivative and / or a pharmacologically acceptable salt thereof together with the compound represented by the general formula (1), an isomer thereof and / or a pharmacologically acceptable salt thereof. In order to exert a potentiating effect on the action or prevention or improvement of pigmentation abnormality, the total amount is 0.001% by mass to 5% by mass, and more preferably 0.1% by mass to 3% by mass with respect to the total amount of the composition. It is preferable to contain. This is because if the amount is too small, the above effect may not be achieved, and if the amount is too large, the effect may reach its peak and the degree of freedom of the system may be impaired.

  Among the melanin production inhibitors, tranexamic acid, its derivatives and / or pharmacologically acceptable salts thereof will be described. The tranexamic acid derivative and / or pharmacologically acceptable salt thereof of the present invention is not particularly limited as long as it is a tranexamic acid derivative having a melanin production inhibitory action and / or a pharmacologically acceptable salt thereof. Can adapt. Specific examples of preferable tranexamic acid derivatives and pharmacologically acceptable salts thereof include tranexamic acid, tranexamic acid methylamide, and / or pharmacologically acceptable salts thereof. More preferable examples include tranexamic acid and / or a pharmacologically acceptable salt thereof.

  The tranexamic acid derivative and / or pharmacologically acceptable salt thereof is a compound represented by the general formula (1), an isomer thereof and / or a pharmacologically acceptable salt thereof. In order to work together and to enhance the effect of preventing or improving pigmentation abnormality due to UV exposure, the total amount is 0.01% by mass to 10% by mass, more preferably 0.05% by mass with respect to the total amount of the composition. -5% by mass, more preferably 0.1% by mass to 3% by mass. This is because if the amount is too small, the above effect may not be achieved, and if the amount is too large, the effect may reach its peak and the degree of freedom of the system may be impaired.

  Among the above melanin production inhibitors, ursolic acid derivatives and / or pharmacologically acceptable salts thereof will be described. The ursolic acid derivatives and their pharmacologically acceptable salts of the present invention are not particularly limited as long as they are ursolic acid derivatives having a melanin production inhibitory action and their pharmacologically acceptable salts. Can adapt without any problem. Specific examples of preferable ursolic acid derivatives and pharmacologically acceptable salts thereof include ursolic acid, ursolic acid phosphate ester (see, for example, WO2006132033), Preferable examples include ursolic acid benzyl ester (see, for example, RE-Table 2007-148474) and / or pharmacologically acceptable salts thereof.

  In addition, the ursolic acid derivative and / or a pharmacologically acceptable salt thereof is a compound represented by the general formula (1), an isomer thereof and / or a pharmacologically acceptable salt thereof. In order to work together with the salt and exert an enhancement effect on the prevention or improvement of pigmentation abnormality, the total amount is 0.001% by mass to 10% by mass, more preferably 0.01% by mass to It is preferable to contain 5 mass%, More preferably, 0.1 mass%-3 mass%. This is because if the amount is too small, the above effect may not be achieved, and if the amount is too large, the effect may reach its peak and the degree of freedom of the system may be impaired.

  Of the aforementioned melanin production inhibitors, vitamin E, its derivatives and / or pharmacologically acceptable salts thereof will be described. Vitamin E of the present invention, its derivatives and / or pharmacologically acceptable salts thereof are special if it is vitamin E having a melanin production inhibitory action, its derivatives and pharmacologically acceptable salts thereof. It can be applied without limitation. Specific examples of preferred vitamin E, derivatives thereof and pharmacologically acceptable salts thereof include vitamin E, vitamin E acetate, vitamin E nicotine, vitamin E oroate and / or Alternatively, pharmacologically acceptable salts thereof can be preferably exemplified, and more preferably, vitamin E and / or pharmacologically acceptable salts thereof can be suitably exemplified.

  In addition, the vitamin E, derivative thereof and / or pharmacologically acceptable salt thereof is a compound represented by the general formula (1), an isomer thereof and / or a pharmacologically acceptable salt thereof. In order to work together with the salt and exert an enhancement effect on the prevention or improvement of pigmentation abnormality, the total amount is 0.05% by mass to 10% by mass, more preferably 0.2% by mass to 5 mass%, More preferably, it is preferable to contain 0.5 mass%-3 mass%. This is because if the amount is too small, the above effect may not be achieved, and if the amount is too large, the effect may reach its peak and the degree of freedom of the system may be impaired.

  Among the melanin production inhibitors described above, pantethein-S-sulfonic acid and / or a pharmacologically acceptable salt thereof will be described. The pantethein-S-sulfonic acid of the present invention can be used not only in a free acid form but also in a salt form. The salt of pantethein-S-sulfonic acid can be used without particular limitation as long as it is a pharmacologically acceptable salt. For example, alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as calcium salt and magnesium salt, organic amine salts such as ammonium salt, triethylamine salt, triethanolamine salt, monoethanolamine salt, lysine salt, Preferred examples include basic amino acid salts such as alginates. Of these, alkaline earth metal salts are preferable, and calcium salts are particularly preferable. This is because the bioavailability is particularly high when used in the form of a skin external preparation. The pantethein-S-sulfonic acid has optical isomers, and both the D-form and DL-form can be used in the present invention, but the D-form is preferred. In addition, pantethein-S-sulfonic acid and its salts are known compounds, and there are those already marketed as cosmetic raw materials, and such commercial products can be purchased and used. As such a commercially available product, “pantethein S sulfonic acid CA-70” (Mutaku Pharmaceutical Co., Ltd.), which is a calcium salt of pantethine-S-sulfonic acid, can be preferably exemplified.

In addition, the pantethein-S-sulfonic acid and / or a pharmacologically acceptable salt thereof is a compound represented by the general formula (1), an isomer thereof and / or a pharmacologically acceptable salt thereof. In order to work together with the added salt and exert an enhancement effect on the prevention or improvement of abnormal pigmentation, the total amount is 0.001% by mass to 1.0% by mass, and more preferably 0.005%. It is preferable to contain from 0.01% by mass to 0.3% by mass, more preferably from 0.01% by mass to 0.8% by mass. This is because if the amount is too small, the above effect may not be achieved, and if the amount is too large, the effect may reach its peak and the degree of freedom of the system may be impaired.

  The α-MSH production inhibitor will be described. The α-MSH production inhibitor of the present invention can be applied without particular limitation as long as it is a component having an α-MSH production inhibitory action. Examples of the component having an α-MSH production inhibitory action include a component having an action of reducing the amount of c-AMP produced in cultured cells in the α-MSH production inhibitory action evaluation system described in JP-A-2009-0667804. Can be suitably exemplified. As such a component, a plant extract obtained from a plant belonging to the leguminous family Claraaceae can be preferably exemplified, and more preferably, a plant extract obtained from a leguminous family Clara genus Clara can be suitably exemplified. α-MSH production suppressor suppresses intracellular c-AMP production by inhibiting α-MSH production of an important signaling substance involved in melanin production in vivo, or inhibiting intercellular communication. And suppress melanin production.

The α-MSH production inhibitor works together with the compound represented by the general formula (1), isomers thereof and / or pharmacologically acceptable salts thereof, and prevents or improves pigmentation abnormality. In order to exert an enhancing effect, the total amount is 0.00001% by mass to 15% by mass, more preferably 0.0001% by mass to 10% by mass, and more preferably 0.01% by mass to the total amount of the composition. It is preferable to contain 5 mass%. This is because if the amount is too small, the above effect may not be achieved, and if the amount is too large, the effect may reach its peak and the degree of freedom of the system may be impaired.

  The melanocyte dendrite elongation inhibitor will be described. The melanocyte dendrite elongation inhibitor of the present invention can be applied without particular limitation as long as it is a component having a melanocyte elongation inhibitory action. As a component which has the dendrite extension inhibitory action of the melanocyte of this invention, the component which has a dendrite extension inhibitory action in the evaluation of the dendrite extension inhibitory action of the melanocyte of Unexamined-Japanese-Patent No. 2009-0465503 can be illustrated suitably. Specific examples of such ingredients include methyl ophiopogononone B, sophoraflavanone A, plant extracts obtained from Asteraceae Achillea millefolium, plant extracts obtained from Lily family Bakumondo, and the like. In addition to abnormal pigmentation due to increased melanin production, the melanocyte dendrite elongation inhibitor is also effective against abnormal pigmentation caused by increased migration of melanin granules from melanocyte dendrite, which does not contribute much to melanin production.

  The melanocyte dendrite elongation inhibitor works together with the compound represented by the general formula (1), isomers thereof and / or pharmacologically acceptable salts thereof to prevent or improve the pigmentation abnormality. In order to exert the enhancing effect, the total amount is preferably 0.01% by mass to 10% by mass, and more preferably 0.05% by mass to 5% by mass. This is because if the amount is too small, the above effect may not be achieved, and if the amount is too large, the effect may reach its peak and the degree of freedom of the system may be impaired.

The proton pump inhibitor will be described. The proton pump inhibitor of the present invention can be applied without particular limitation as long as it is a component having a proton pump inhibitory action. The proton pump inhibitor is a membrane H ⁺ -ATPase that is present in a biological membrane and actively transports protons, and / or Na ⁺ / H that works in conjunction with Na ⁺ / K ⁺ -ATPase of an ion pump and passively transports protons. ⁺ Acts on exchange transport systems, etc., acts on biological functional molecules that regulate proton concentration in cells or organelles, and excels in inducing acidification in cells or organelles by inhibiting proton transport . Acidification in a cell or organelle has a great influence on the biological activity or function of a biologically functional molecule such as an ion channel or enzyme (for example, tyrosinase) that works in a pH-dependent manner. The tyrosinase enzyme, which is a key enzyme for melanin production, is greatly affected by pH fluctuations, so that acidification reduces tyrosinase activity and suppresses melanin production. As a component which has the proton pump inhibitory action of this invention, the component which shows a proton pump inhibitory action in the proton pump inhibitory action evaluation of Japanese Patent Application No. 2009-219292 can be illustrated suitably, for example. Of the components having proton pump inhibitory activity of the present invention, preferred examples are specifically exemplified: plants belonging to the genus Lamiaceae, genus Clara, plants belonging to the genus Clariaceae, cucurbitaceae A plant extract obtained from a plant belonging to the genus Hechima, a plant belonging to the genus Hydrangeaceae, a plant belonging to the genus Sarcophagus matsuhodo, a plant belonging to the genus Leguminosae, can be preferably exemplified, more preferably, Obtained plant extract, plant extract obtained from leguminous clara genus clara, plant extract obtained from ginger family ginger genus ginger, plant extract obtained from taro family ginger genus ginger, obtained from cucurbitaceae Plant extract, plant extract obtained from Hydrangea hydrangea amacha, Sarnokoshika Plant extracts obtained from family Wolfiporia Extensa sclerotia Bukuryou, plant extract obtained from leguminous clover genus Kihagi, plant extract obtained from leguminous gores genus Toukusahagi be suitably be exemplified.

  The component having the proton pump inhibitory action works together with the compound represented by the general formula (1), isomers thereof and / or pharmacologically acceptable salts thereof, and prevents or improves the pigmentation abnormality. In order to exert an enhancing effect on the total amount of the composition, the total amount is 0.000001% by mass to 10% by mass, more preferably 0.00001% by mass to 5% by mass, and still more preferably 0.0001% by mass. It is preferable to contain -3 mass%. This is because if the amount is too small, the above effect may not be achieved, and if the amount is too large, the effect may reach its peak and the degree of freedom of the system may be impaired.

  In addition, among simple whitening agents such as melanin production inhibitors, α-MSH inhibitors, melanocyte dendrite elongation inhibitors, proton pump inhibitors and the like, which are essential components of the present invention, the compounds may be used as they are. It can be used as a pharmacologically acceptable salt form. These salts can be used without any particular limitation as long as they are used in skin external preparations, for example, alkali salts such as sodium salts and potassium salts, calcium salts, magnesium salts, etc. Preferred examples include alkaline earth metal salts, ammonium salts, triethylamine salts, triethanolamine salts, organic amine salts such as monoethanolamine salts, and basic amino acid salts such as lysine salts and alginates. Moreover, as long as it is a salt with an acid, mineral acid salts, such as hydrochloride, phosphate, sulfate, and nitrate, organic acid salts, such as carbonate, citrate, and tartrate, etc. can be illustrated suitably.

  Such a whitening component is included in the composition together with the compound represented by the general formula (1), its isomer and / or a pharmacologically acceptable salt thereof, thereby allowing excellent pigmentation by exposure to ultraviolet rays. This shows the effect of enhancing the prevention or improvement of pigmentation caused by excessive production of melanin by stimulation such as exposure to ultraviolet rays, and particularly, the prevention or improvement of prevention. Such an enhancement effect of preventing or improving pigmentation is caused by the pharmacological effect of the compound represented by the general formula (1), its isomer and / or pharmacologically acceptable salt, and a whitening component. This is considered to be due to the effect of improving the delivery efficiency of the whitening component to the target site, as well as the pharmacological activity of the compound represented by the general formula (1), in addition to the additive or synergistic effect.

<Composition of the present invention>
The composition of the present invention comprises 1) a compound represented by the general formula (1), an isomer thereof and / or a pharmacologically acceptable salt thereof, and 2) a whitening component. To do. The compound represented by the general formula (1) of the present invention, its isomers and / or pharmacologically acceptable salts thereof are contained in the composition together with the above-described whitening component, whereby a whitening action, specifically Specifically, it shows the effect of enhancing the effect of preventing or improving pigmentation by exposure to ultraviolet rays, particularly the effect of enhancing the effect of preventing or improving pigmentation caused by excessive production of melanin by stimulation such as exposure to ultraviolet rays. Such an enhancement effect of preventing or improving pigmentation is caused by the pharmacological effect of the compound represented by the general formula (1), its isomer and / or pharmacologically acceptable salt, and a whitening component. In addition to an additive or synergistic effect, the effect of improving the delivery efficiency of the whitening component to the target site, and further, the compound represented by the general formula (1), its isomer and / or their pharmacological properties It is thought to be due to pharmacological activity such as whitening effect of the acceptable salt. In addition, the above-mentioned ultraviolet ray exposure causes abnormal pigmentation, and at the same time, overproduction of melanin in melanocytes, and cell inactivation of keratinocytes such as excessive transport, accumulation and elimination of melanin to keratinocytes, It is observed that skin symptoms are aggravated by damage such as turnover delay. The composition of the present invention is preferably used for a person who exhibits rough skin symptoms caused by excessive production and transport of melanin in addition to preventing or ameliorating abnormal pigmentation. When a person with such skin symptoms is observed, phenomena such as an increase in nucleated cells and delamination are observed. Therefore, it is also effective to narrow down the target to be used using these as an index.

In addition, a preparation of a composition comprising 1) a compound represented by the general formula (1), an isomer thereof and / or a pharmacologically acceptable salt thereof, and 2) a whitening component. In preparation, it can contain optional components used in the preparation of ordinary foods, pharmaceuticals, cosmetics and the like. Examples of such optional components include oral excipients such as excipients such as lactose and white sugar, binders such as starch, cellulose, gum arabic, and hydroxypropyl cellulose, carboxymethyl cellulose, Disintegrants such as sodium and carboxymethylcellulose calcium, surfactants such as soy lecithin and sucrose fatty acid ester, sweeteners such as malt and sorbitol, sour agents such as citric acid, phosphates, etc. Buffering agents, film forming agents such as shellac and zein, lubricants such as talc and wax, glidants such as light anhydrous silicic acid and dry aluminum hydroxide gel, diluents such as physiological saline and aqueous glucose solution, Suitable examples include flavoring agents, coloring agents, bactericides, preservatives, and fragrances.

As the composition of the present invention, pharmaceuticals, cosmetics, foods, beverages and the like can be suitably exemplified, and since they can be taken on a daily basis, it is preferable to adapt to foods, cosmetics and the like. The administration route can be either oral administration or transdermal administration. For the purpose of detoxification (detox), oral administration with high efficiency in reaching the relevant organ is adopted, and forms of oral administration compositions such as foods Is preferably adopted. Moreover, when such a component is continuously administered, and further considering safety, it is preferably administered transdermally. As long as it can be applied to the skin for external use, it can be applied without particular limitation. For example, cosmetics including quasi-drugs, external preparations for skin, miscellaneous items for external use, etc. can be preferably exemplified. 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 and the like can be suitably exemplified, It is particularly preferable to apply to cosmetics. 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. The cosmetic is not particularly limited as long as the water-in-oil emulsifier form can be applied. For example, basic cosmetics such as essence, milky lotion, cream, under-makeup, foundation, -Makeup cosmetics such as kukara, mascara and eyeliner, hair cosmetics such as hair cream, etc. can be preferably exemplified.

The external preparation for skin of the present invention can contain, in addition to such components, optional components that are usually used in external preparations for skin. Such optional ingredients include, for example, macadamia nut oil, avocado oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower oil, cottonseed oil, jojoba oil, palm oil, palm oil, liquid Lanolin, hydrogenated coconut oil, hydrogenated oil, molasses, hydrogenated castor oil, beeswax, candelilla wax, carnauba wax, ibotarou, lanolin, reduced lanolin, hard lanolin, jojoba wax, oils, waxes; liquid paraffin, squalane, pristane, ozokerite, Hydrocarbons such as paraffin, ceresin, petrolatum, 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 -Le, Isosteari Higher alcohols such as alcohol, behenyl alcohol, octyldodecanol, myristyl alcohol, cetostearyl alcohol; cetyl isooctanoate, isopropyl myristate, hexyldecyl isostearate, diisopropyl adipate, sebacic acid Di-2-ethylhexyl, cetyl lactate, diisostearyl malate, ethylene glycol di-2-ethylhexanoate, neopentyl glycol dicaprate, glycerin di-2-heptylundecanoate, glycerin tri-2-ethylhexanoate Synthetic ester oils such as trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, pentane erythritol tetra-2-ethylhexanoate; dimethylpolysiloxane, methylphenylpoly Chain polysiloxanes such as Loxane and diphenylpolysiloxane; Cyclic polysiloxanes such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, and dodecamethylcyclohexanesiloxane; Amino-modified polysiloxane, polyether-modified polysiloxane, and alkyl-modified polysiloxane , Oil agents such as silicone oils such as modified polysiloxane such as fluorine-modified polysiloxane; anionic surfactants such as fatty acid soap (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, triethanolamine alkyl sulfate ; Cationic surfactants such as stearyltrimethylammonium chloride, 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 (such as glyceryl monostearate), propylene glycol fatty acid esters (such as propylene glycol monostearate), hardened castor oil derivatives, glycerin alkyl ether 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 ether, 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 ester, alkyl glucoside; moisturizing ingredients such as sodium pyrrolidone carboxylate, lactic acid, sodium lactate; surface treatment May be 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- UV absorbers such as 5′-t-octylphenyl) benzotriazole and 4-methoxy-4′-t-butyldibenzoylmethane; lower alcohols such as ethanol and isopropanol; vitamin A or a derivative thereof Vitamin B6 such as vitamin B6 hydrochloride, vitamin B6 tripalmitate, vitamin B6 dioctanoate, vitamin B2 or a derivative thereof, vitamin B12, vitamin B15 or a derivative thereof; α-tocopherol, β-tocopherol, Vitamin E such as γ-tocopherol, vitamin E acetate, vitamin D, vitamin H, punt Phosphate, pantethine, vitamins pyrroloquinoline quinone such like; phenoxyethanol - antibacterial agents such as Le; hectorite, and organic-modified clay minerals such as dimethyl distearyl ammonium modified hectorite may be preferably exemplified.

Among such optional components, organically modified clay minerals are particularly preferable. Here, organic modification means that a part or all of the properties of an organic compound is made into a clay mineral by causing a part of the organic compound to form a strong or loose bond via a covalent bond or an ionic bond. This means that it is imparted to minerals. Examples of such modifications include a method of binding a quaternary amine group and an anion portion of a clay mineral, and a method of binding a carboxyl group and a cation portion of a clay mineral. A method of combining the group and the anion portion of the clay mineral is particularly preferable. Although it does not necessarily limit as a compound which has a quaternary amino group which modifies a clay mineral, The compound called quaternium is illustrated. Quotanium is a low molecular weight substituted quaternary ammonium salt, and is preferably a cosmetic raw material registered in International Standard Cosmetic Ingredients (INCI). Furthermore, the compound having a quaternary amino group that modifies the clay mineral is preferably a quaternium compound contained in a conventional external skin preparation among quaternium compounds. Preferred examples of the quaternium compound used in conventional external preparations for skin include stearyl trimethyl ammonium chloride and dimethyl distearyl ammonium chloride. Among them, dimethyl distearyl ammonium chloride is particularly preferable. This is because two long-chain alkyl groups are contained in one molecule, so that it is easy to make a structure that sterically holds the oil phase. Stearyl trimethyl ammonium chloride, dimethyl distearyl ammonium chloride, and the like are preferable because they can form a stable aqueous oil-in-water component emulsion structure together with clay minerals. In particular, when the aqueous component is an oil-in-water emulsion, an emulsion having a continuous phase as an oil phase can be formed without significantly affecting the oil-in-water emulsion. preferable. On the other hand, as a clay mineral (unmodified clay mineral) modified with a compound having a quaternary amino group, any clay mineral contained in a conventional external preparation for skin can be used without particular limitation. Examples of clay minerals contained in conventional external preparations for skin include smectite-type hectorite, bentonite and montmorillonite; kaolinite; illite; marine clay mineral (sea mud); dezatroze clay mineral; Preferably mentioned. Among these, bentonite, hectorite, montmorillonite or kaolinite which can stabilize the water-in-oil emulsion structure is preferably exemplified. Among them, hectorite and montmorillonite are particularly preferable because they have a firm layer structure in minerals and can easily orient cation molecules. An example of a method for producing a clay mineral modified with a compound having a quaternary amino group contained in the external preparation for skin of the present invention will be described below. The unmodified clay mineral is dispersed in a dispersion medium. The dispersant is preferably an aqueous solvent, and may be water. A compound having a quaternary amino group is further added to the dispersion containing the dispersed unmodified clay mineral and stirred well. The compound having a quaternary amino group may be added after being dissolved in water. The amount of the compound having a quaternary amino group to be added is preferably 0.1 to 20% by mass, and more preferably 0.5 to 15% by mass with respect to the amount of the dispersed unmodified clay mineral. This is because by taking such a configuration, a preferable feeling of use is exhibited in the emulsification system. After stirring, the dispersoid is filtered, dehydrated and dried to obtain the modified clay mineral in the present invention. Or the modified clay mineral in this invention can also be obtained by removing a dispersing agent by concentrating under reduced pressure without filtering a dispersoid, and making it dry. The obtained modified clay mineral is preferably pulverized to a desired size (preferably having a particle size of 1 to 1000 μm) and contained in the skin external preparation of the present invention. The modified clay mineral in the present invention can be prepared and used as described above, but a commercially available one can also be used. Some modified clay minerals on the market are used as external preparations for skin such as cosmetics. Preferable examples of commercially available modified clay minerals include dimethyl distearyl ammonium modified hectorite sold under the name “Benton 38V” by Elementis. In the skin external preparation of this invention, this component is contained preferably 0.5 mass%-10 mass%, More preferably, 1 mass%-5 mass% are contained. In such a range, the compound represented by the general formula (1) or the whitening component can be stabilized and formulated into a water-in-oil emulsifier form. Here, the water-in-oil emulsifier form described in the present invention is a general term for an emulsifier form in which an oil phase is present in the outermost phase, a form in which water phase drops are dispersed in the oil phase, and an oil-in-water emulsified drop in the oil phase. Any form in which the is dispersed can be employed. In addition, when employ | adopting such a water-in-oil emulsifier form, it is preferable to contain 0.1-5 mass% of polyether modified methyl polysiloxane as an auxiliary | assistant surfactant. Such polyether-modified methylpolysiloxanes are commercially available, and such commercially available products can be purchased and used. As a preferable commercial product, “Silicon KF6017” manufactured by Shin-Etsu Chemical Co., Ltd. can be suitably exemplified. In the present invention, the water-in-oil emulsifier form means an emulsion in which the oil phase is present as a continuous phase in the outermost phase, and the emulsifier form in which water droplets are dispersed in the continuous phase is also dispersed in the oil-in-water emulsion. Also included are O / W / O emulsifiers present as drops.

When diglycerin monooleate and / or triglycerin diisostearate is contained as an emulsifier, a polyhydric alcohol such as a multi-toll or sorbitol having a mass of 0.5 to 2 times the mass of the emulsifier. -It is preferable to contain together. Preferred examples of the raw material for the diglycerin monooleate cosmetics include “Nikko DGMO-C” (manufactured by Nippon Surfactant Co., Ltd.), and triglycerin diisostearate for cosmetics. Preferred examples of the raw material include “Emerest 2452” (manufactured by Emery). The preferable content of this component is 1 to 10% by mass, more preferably 2 to 7% by mass, based on the total amount of the external preparation for skin. This is because if the amount is out of this range, emulsification may not be possible or the stability of the solution may be impaired.

In the external preparation for skin of the present invention, in addition to the above components, oily components and aqueous components are difficult to dissolve, especially non-polar components such as silicones such as dimethicone and hydrocarbons such as liquid paraffin. Preferable examples of the component that contains a hardly soluble component and is difficult to dissolve include phytosterol glycosides and glycosphingolipids. Such an ingredient is an active ingredient having preferable functions such as a photoaging prevention effect, a turnover adjusting effect, a moisturizing effect on the skin, and the phytosterol is a phytosterol. The plant-based sterols include stigmasterol, campesterol, sitosterol, and the like, and these are collectively referred to as phytosterol. A phytosterol glycoside is obtained by binding a sugar chain to this phytosterol. As the phytosterol glycoside, a sterol containing a plurality of phytosterol glycosides from a plant such as wheat germ is used. -Glucose glycoside fractions are often taken out and used, and cosmetic raw materials obtained by purifying only such fractions are also commercially available, and such commercial raw materials of the present invention can be purchased and used. Usually, such components often contain glycosphingolipids extracted at the same time. Examples of such commercially available materials include “Phytosteside” sold by Okayasu Shoten Co., Ltd. About 85% by mass of such “phytosteside” is a glycoside of phytosterol, and about 15% by mass is a glycosphingolipid. The preferable content of such an insoluble active ingredient, especially a solid component, is 0.05 to 0.5% by mass.

Since the external preparation for skin of the present invention takes the form of a water-in-oil emulsifier form, in order to compensate for the drawbacks of the feeling of use and finish of the water-in-oil emulsifier form, silicone, particularly preferably cyclomethicone and / or It is preferable to contain dimethicone having a viscosity of 1 mPa · s or less, and the content of the silicone is preferably 10 to 50% by mass, more preferably 20 to 40% with respect to the total amount of the cosmetic. The sum of the contents of cyclomethicone and dimethicone having a viscosity of 1 mPa · s or less is 50% by mass or more, more preferably 55% by mass or more, based on the total amount of the oil phase.

Since the external preparation for skin of the present invention takes the form of a water-in-oil emulsifier form, in order to compensate for the drawbacks of the feeling of use and finish of the water-in-oil emulsifier form, silicone, particularly preferably cyclomethicone and / or It is preferable to contain dimethicone having a viscosity of 1 mPa · s or less, and the content of the silicone is preferably 10 to 50% by mass, more preferably 20 to 40% with respect to the total amount of the cosmetic. The sum of the contents of cyclomethicone and dimethicone having a viscosity of 1 mPa · s or less is 50% by mass or more, more preferably 55% by mass or more, based on the total amount of the oil phase.

Moreover, in the skin external preparation of this invention, when using the said organic modified clay mineral as an emulsifier, in the meaning which assists the emulsification effect | action of the said organic modified clay mineral, POE modified methylpolysiloxane, POP modified methylpolysiloxane, POP · POE A suitable example is the inclusion of a polyether-modified methylpolysiloxane such as a modified methylpolysiloxane. The preferable content of such polyether-modified methylpolysiloxane is more preferably 0.5 to 5% by mass and 1 to 3% by mass.

When the organically modified clay mineral is used as an emulsifier, a preferred optional component other than the above-described components can be exemplified by a polyhydric alcohol that can stabilize the emulsified state. Particularly preferred are glycerin, diglycerin and dipropylene glycol. Such a component may contain only one species or may contain two or more species in combination. A preferable content is 5-30 mass% with respect to the total amount of skin external preparations in total, More preferably, it is 10-25 mass%. In addition, it may contain 3 to 7% by mass of one or more selected from 1,2-pentanediol, 1,2-hexanediol and 1,2-octanediol. It is preferable from the viewpoint of improving power.

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.

<Production Example 7: Method 1 for producing skin external preparation of the present invention>
A water-in-oil emulsifier type cosmetic (cream) was prepared according to the formulations described in Tables 1 and 2. That is, each of the components (a), (b), and (c) is heated to 80 ° C., and (d) is added and dissolved in (b), kneaded to form a gel, and added to (b), diluted, and gradually stirred with stirring. The mixture was emulsified with water, stirred and cooled to prepare cosmetics 1 to 11 in the form of a water-in-oil emulsifier, which is a skin external preparation of the present invention. In the same manner, Comparative Example 1 in which “the compound represented by the general formula (1) of the present invention” was replaced with “water” in the formulation component of the cosmetic 1, and “the whitening component of the present invention” was replaced with “water”. A comparative example 2 in which “the compound represented by the general formula (1) of the present invention” and “a whitening component of the present invention” were both replaced with “water” was prepared.

<Test Example 1: Evaluation 1 of pigmentation inhibitory effect of the external preparation for skin of the present invention>
The pigmentation inhibitory effect was investigated using the water-in-oil emulsifier type cosmetics (cosmetics 1-11) and the cosmetics of Comparative Examples 1-3. 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 (cosmetics 1-11 or 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. The skin lightness (L * value) of each test site was measured with a color difference meter (CR-300, Konica Minolta Co., Ltd.) 24 hours after the application was finished (15th day), and ΔL * value relative to the L value on the first day of the test. Was calculated. The results are shown in Table 3. Since the ΔL * value decreases as the degree of pigmentation increases, it can be determined that the pigmentation is suppressed as the ΔL * value increases. Thereby, it turns out that the cosmetics 1-11 which are the skin external preparations of this invention have 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 the cosmetics 1-11. Thereby, it turns out that the cosmetics 1-11 which are the skin external preparations of this invention show the outstanding pigmentation inhibitory effect.

<Production Example 8: Method 2 for producing external preparation for skin of the present invention>
Example 1 describes cosmetics in which the contents of the “compound represented by the general formula (1) of the present invention” and “whitening component of the present invention” contained in the cosmetics 1 to 3 are changed. The pigmentation inhibitory effect by ultraviolet exposure was examined. The content of the components is as described in Table 4. Moreover, the change of the mass% by the increase / decrease in the said component was adjusted by increasing / decreasing the mass% of water.

<Test Example 2: Evaluation 2 of pigmentation inhibitory effect of the external preparation for skin of the present invention>
The water-in-oil emulsifier type cosmetics 12 to 17 produced by the method described in Example 3, and further, Comparative Example 3 produced according to the method described in Example 1, and the pigment according to the test method described in Example 2 The deposition inhibitory action was evaluated. The results are shown in Table 5. From the results in Table 5, it can be seen that the cosmetics 12 to 17 which are the external preparation for skin of the present invention show an excellent pigmentation inhibitory effect.

<Test Example 3: Evaluation of pigmentation inhibitory effect 3 of the external preparation for skin of the present invention>
In the prescription ingredients of cosmetic 1 described in Example 1, cosmetic 18 in which “Benton 38V” is replaced with “silicon KF6017”, and “1,2-pentanediol” in “polyethylene glycol 400” A substituted cosmetic 19 was prepared. Furthermore, regarding the cosmetic 18, the cosmetic 19, and the comparative example 3, when the pigmentation inhibitory action by ultraviolet exposure was evaluated according to the method described in Example 2, the ΔL * value of the cosmetic 18 was −4.01, The ΔL * value of the cosmetic 19 is −4.03, and the ΔL * value of the comparative example 3 is −4.11. In any cosmetic, the pigmentation suppression effect by exposure to ultraviolet rays is almost the same. I was not able to admit.

<Test Example 4: Evaluation of inhibitory effect on pigmentation of skin external preparation of the present invention 4>
For cosmetics 1 to 3 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. When selecting a panel with a higher melanin content than the average, a sample of stratum corneum cells collected from the skin by adhesive tape stripping is visualized by melanin staining using an aqueous silver nitrate solution and observed under a microscope. It was judged by. In the determination, the determination was made by scoring around the average existence situation. Further, among the panelists, a person who has a higher nucleated cell appearance rate than the average using a stratum corneum specimen or has a higher degree of delamination than the average was selected by observation and designated as a paneler. The part of 1.5cm x 1.5cm is divided into two upper and lower tiers on the inner side of both upper arms of the panelists who participated voluntarily with the above-mentioned characteristics. Irradiation was performed once a day for 3 consecutive days. From 1 day after the completion of irradiation, 50 μL of sample was applied once a day for 28 consecutive days. One site was an untreated site. 24 hours after the completion of application, the skin lightness (L * value) of each test site was measured with a color difference meter (CR-300, Konica Minolta Co., Ltd.), and ΔL * value relative to the L value of the untreated site was calculated. The L * value decreases as the degree of pigmentation increases. Therefore, it can be determined that the greater the ΔL * value, the more pigmentation is suppressed. The results are shown in Table 6. Thereby, it turns out that the cosmetics 1-3 which are the skin external preparations of this invention show the outstanding pigmentation inhibitory effect.

<Production Example 9: Production of health food of the present invention>
According to the prescription shown in Table 7 and Table 8, health foods (health foods 1 to 11) were prepared. That is, the prescription ingredients were tumbled phase granulated with 10 parts by weight of water (“New Malmerizer” manufactured by Fuji Powder Co., Ltd.) and tableted to obtain a tablet-like health food. In addition, the unit of the numerical value in a table | surface represents a weight part. This health food had excellent pigmentation prevention or improvement action.

  The present invention can be applied to whitening cosmetics, foods and the like.

Claims (21)

A composition comprising 1) a compound represented by the following general formula (1), an isomer thereof and / or a pharmacologically acceptable salt thereof, and 2) a whitening component.

(1)
[Wherein, R1 represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, and R2 has a hydrogen atom, an aromatic group having no substituent or a substituent, an unsubstituted group or a substituent. Represents an aliphatic hydrocarbon group having 1 to 4 carbon atoms substituted by an aromatic group, R3 represents an unsubstituted or substituted aromatic group, n represents an integer of 1 or 2, and m represents 0. Represents an integer of ~ 3. ] The compound represented by the general formula (1) is a compound represented by the following general formula (2), an isomer thereof and / or a pharmacologically acceptable salt thereof, Item 2. The composition according to Item 1.

(2)
[Wherein, R4 represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, R5 represents an unsubstituted or substituted aromatic group, and n is an integer of 1 or 2. , M represents an integer of 0 to 3. ] The compound represented by the general formula (2) is a compound represented by the following general formula (3), an isomer thereof and / or a pharmacologically acceptable salt thereof, Item 3. The composition according to Item 1 or 2.

(3)
[Wherein, R6 represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, R7 represents an unsubstituted or substituted aromatic group, and n is an integer of 1 or 2. Represents. ] The compound represented by the general formula (3) is a compound represented by the following general formula (4), an isomer thereof and / or a pharmacologically acceptable salt thereof, Item 4. The composition according to any one of Items 1 to 3.

(4)
[Wherein, R8 represents a hydrogen atom or a linear or branched alkyl group having 1 to 8 carbon atoms, and R9 represents an unsubstituted or substituted aromatic group. ] The compounds represented by the general formulas (1) to (4) are N- (o-toluyl) cysteic acid (compound 1), N- (m-toluyl) cysteic acid (compound 2), N- (p- Toluyl) cysteic acid (compound 3), N- (p-methoxybenzoyl) cysteic acid (compound 4), (N-biphenylcarbonyl) cysteic acid (compound 5), N- (p-toluyl) homocysteic acid (compound 6) ), Isomers thereof and / or pharmacologically acceptable salts thereof, 5. The composition according to any one of claims 1 to 4.

N- (o-Toluyl) cysteic acid (Compound 1)

N- (m-Toluyl) cysteic acid (Compound 2)

N- (p-Toluyl) cysteic acid (Compound 3)

N- (p-methoxybenzoyl) cysteic acid (compound 4)

(N-biphenylcarbonyl) cysteic acid (Compound 5)

N- (p-Toluyl) homocysteic acid (Compound 6) The compound represented by the general formula (1), its isomer and / or pharmacologically acceptable salt thereof is contained in an amount of 0.0001% by mass to 20% by mass with respect to the total amount of the composition. The composition according to any one of claims 1 to 5. The whitening component contains one or more selected from the group consisting of a melanin production inhibitor, an α-MSH inhibitor, a melanocyte dendrite elongation inhibitor, and a proton pump inhibitor. Item 7. The composition according to any one of Items 1 to 6. The one selected from the group consisting of the melanin production inhibitor, α-MSH inhibitor, melanocyte dendrite elongation inhibitor and proton pump inhibitor is any of the following: A composition according to 1.
(Melanin production inhibitor): 4-alkylresorcinol and / or salt thereof, ascorbic acid derivative and / or salt thereof, hydroquinone and / or salt thereof, tranexamic acid derivative and / or salt thereof, Ursolic acid derivative and / or salt thereof, vitamin E and / or derivative thereof, pantethein-S-sulfonic acid and / or salt thereof (α-MSH inhibitor): plant extract obtained from legume Clara (Melanosite dendriide elongation inhibitor): Methyl ophiopogononone B, Sophoraflavanone A, Plant extract obtained from Asteraceae Achillea millefolium, Plant extract obtained from Liliaceae saccharum (proton pump inhibitor) Plant extract obtained from Musk genus Thyme, plant extract obtained from Clariaceae Clara , Plant extract obtained from ginger ginger genus ginger, plant extract obtained from taro family ginger genus ginger, plant extract obtained from cucurbitaceae genus gneiss, plant extract obtained from saxifragae hydrangea amacha, A plant extract obtained from the sorghum pine fungus nuclei, a plant extract obtained from the leguminous genus kihagi, a plant extract obtained from the leguminous sage The said whitening component contains 0.000001-15 mass% with respect to the composition whole quantity, The composition as described in any one of Claims 1-8 characterized by the above-mentioned. The composition according to any one of claims 1 to 9, wherein the composition is a cosmetic (however, including a quasi-drug). The composition according to any one of claims 1 to 10, wherein the composition is for whitening. The composition according to any one of claims 1 to 11, which is used for prevention or improvement of pigmentation due to ultraviolet exposure. The composition according to any one of claims 1 to 12, which is used for prevention or improvement of pigmentation abnormality involving cell inactivation of keratinocytes caused by melanin overtransport. It is a skin external preparation, The composition as described in any one of Claims 1-13 characterized by the above-mentioned. A skin external preparation characterized by comprising 1) a compound represented by the general formula (1), an isomer thereof and / or a pharmacologically acceptable salt thereof, and 2) a whitening component. The compound represented by the general formula (1), its isomer and / or pharmacologically acceptable salt thereof is converted into the compound represented by the general formula (4), its isomer and / or their isomer. The external preparation for skin according to claim 15, which is a pharmacologically acceptable salt. The compound represented by the general formula (1) is N- (o-toluyl) cysteic acid (compound 1), N- (m-toluyl) cysteic acid (compound 2), N- (p-toluyl) cysteic acid. (Compound 3), N- (p-methoxybenzoyl) cysteic acid (Compound 4), (N-biphenylcarbonyl) cysteic acid (Compound 5), N- (p-toluyl) homocysteic acid (Compound 6), isomers thereof The external preparation for skin according to claim 15, which is a body and / or a pharmacologically acceptable salt thereof.

N- (o-Toluyl) cysteic acid (Compound 1)

N- (m-Toluyl) cysteic acid (Compound 2)

N- (p-Toluyl) cysteic acid (Compound 3)

N- (p-methoxybenzoyl) cysteic acid (compound 4)

(N-biphenylcarbonyl) cysteic acid (Compound 5)

N- (p-Toluyl) homocysteic acid (Compound 6) The whitening component contains one or more selected from the group consisting of a melanin production inhibitor, an α-MSH inhibitor, a melanocyte dendrite elongation inhibitor, and a proton pump inhibitor. The skin external preparation according to any one of Items 15 to 17. The material selected from the group consisting of the melanin production inhibitor, an α-MSH inhibitor, a melanocyte dendrite elongation inhibitor and a proton pump inhibitor is any of the following: The skin external preparation as described in any one of these.
(Melanin production inhibitor): 4-alkylresorcinol and / or salt thereof, ascorbic acid derivative and / or salt thereof, hydroquinone and / or salt thereof, tranexamic acid and / or derivative thereof, ursolic acid, Derivatives thereof and / or salts thereof, vitamin E and / or derivatives thereof, pantethein-S-sulfonic acid and / or salts thereof (α-MSH inhibitor): plant extracts obtained from the legume Clara genus Clara Dendride Elongation Inhibitor): Methyl ophiopogononone B, Sophoraflavanone A, Plant extract obtained from Asteraceae Achillea millefolium, Plant extract obtained from Liliaceae Aegypti (proton pump inhibitor): Lamiaceae Plant extract obtained from leguminous family Clara genus Clara, show Plant extract obtained from ginger family ginger, plant extract obtained from taro family ginger genus, plant extract obtained from cucurbitaceae ginkgo genus, plant extract obtained from saxifragae hydrangea amacha, sarnococcaceae matsuhod Plant extract obtained from mycorrhizal nucleus, plant extract obtained from leguminous genus kihagi, plant extract obtained from legume genus genus The skin external preparation according to any one of claims 15 to 19, which is in the form of a water-in-oil emulsifier. Furthermore, the preferable preparation component is contained, The skin external preparation as described in any one of Claims 15-20 characterized by the above-mentioned.