JP5820572B2 - Composition - Google Patents

Description

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

AB (1)
[In the formula (1) , A represents a di- or triaromatic methyl group, and the aromatic is selected from the group consisting of an unsubstituted or substituted aryl group and an unsubstituted or substituted heteroaromatic ring. Each is chosen independently. In formula (1), B represents a hydrogen atom, a hydrogen atom, or a cyclic or non-cyclic aliphatic hydrocarbon group in which the carbon atom may be substituted with a hetero atom , or an aromatic Represents a group hydrocarbon group. ]

Skin symptoms such as wrinkles, spots and sagging are skin aging symptoms that manifest with aging due to accumulation of physicochemical stimuli such as temperature changes, ultraviolet rays and chemical exposure in addition to genetic factors. Such skin symptom greatly affects the appearance of others, so keeping the skin aesthetics is an important concern for people. Among these skin symptoms, it has been clarified that skin symptoms such as blotches, freckles, and pigmentation after sunburn are caused by increased melanin production by activation of pigment cells (melanocytes) present in the skin. . Excessive or chronically increased melanin production in melanocytes can be cured by inducing melanin excess transport to keratinocytes (keratinocytes), accumulation, and delayed discharge, and inactivating cell functions of keratinocytes. hard spots, dullness, cause pigmentation associated with the deterioration of the skin symptoms of layer separation, and the like. In order to prevent or improve pigmentation including deterioration of skin symptoms caused by such increased melanin production, various active ingredients including whitening agents have been researched and developed. In particular, development of components having a whitening effect are actively conducted, for example, ascorbic acid, hydrogen peroxide, colloidal sulfur, glutathione, hydroquinone and whitening agents such as catechol Lumpur such known, was blended the ingredients Skin external preparations are also widely used (see, for example, Non-Patent Document 1 and Non-Patent Document 2). In addition to research on whitening agents, detailed research on pigmentation mechanisms has also been conducted, and whitening agents having various mechanisms of action based on the results, such as melanin production inhibitors (see, for example, Patent Document 1), tyrosina over enzyme inhibitors (e.g., see Patent Document 2), tyrosinase over enzyme gene expression inhibitor, alpha-MSH inhibitor (e.g., see Patent Document 3), antioxidants (e.g., see Patent Document 4 ) Etc. have been reported.

  In addition, as an attempt to achieve a high whitening effect by including a whitening component in a composition containing a whitening agent, in particular, an external preparation for skin, creation of a new whitening active ingredient (see, for example, Patent Document 5) ) In addition to combining a plurality of whitening active ingredients (see, for example, Patent Document 6), and further improving the skin permeability or storage ability (see, for example, Patent Document 7) by devising prescription ingredients Etc. are done. However, in skin external preparations containing a whitening agent, skin external preparations containing a plurality of whitening agents, and skin external preparations designed to enhance the whitening effect, for normal pigmentation, Although a certain whitening effect is recognized, the effect is not always satisfactory. In particular, it is difficult to say that the whitening effect is sufficient for pigmentation in which a decrease in cell function of keratinocytes is involved. In fact, people with incurable skin or dullness that involve a decrease in cellular function of keratinocytes, or pigmentation with rough skin such as delamination, give the skin a dull impression and improve this dullness. Therefore, it has been desired to develop a means for improving the darkness of such a person. Moreover, the said whitening agent and the skin external preparation which mix | blended the said component existed that had a subject in stability and safety. Furthermore, through extensive research and research on whitening ingredients so far, material resources such as natural products or synthetic compounds have been extensively researched and it is predicted that the creation of new active ingredients will be more difficult than ever. Therefore, a technique for effectively exerting the whitening action of the conventional whitening component has attracted attention, and the development of the technique is further desired.

Steric bulky aromatic groups or heteroaromatic groups (particularly diphenylmethyl or triphenylmethyl groups) are widely known as effective protecting groups for hydroxyl groups or amino groups in organic low molecular weight compounds, peptides and nucleic acid synthesis. (For example, see Non-Patent Document 3 and Non-Patent Document 4). Reactions and intermediate compounds using these protecting groups (e.g., see Non-Patent Document 5 and Non-Patent Document 6) has been applied to the organic synthesis in wide scale Lumpur to industrial production from the laboratory. In addition, regarding the compound having such a sterically bulky substituent in its chemical structure, antitumor activity (see, for example, Non-Patent Document 5), antifungal action (see, for example, Patent Document 8) Exhibit pharmacological activities such as antihistamine action (see, for example, Non-Patent Document 6), dopamine uptake inhibitory action (see, for example, Non-Patent Document 7), calcium antagonism (see, for example, Non-Patent Document 8), etc. Has been reported. However, it has not been known at all that the effect of preventing or improving pigmentation is enhanced by including the compound represented by the general formula (1) in the composition together with the whitening component. In addition, such compositions are also known to be effective against pigmentation associated with incurable healing, dullness, and rough skin caused by phenomena such as excessive transport of melanin to keratinocytes due to increased melanin production, accumulation and delayed discharge. There wasn't.

JP 2008-208073 A JP 2009-196895 A JP 2001-220347 A JP 2010-037299 A JP 2009-263258 A JP 2004-352630 A JP 2007-332115 A JP 09-255634 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 Theodora W. Green, Protective Groups in Organic Synthesis, A Wiley-Interscience Publication .: 1981, P173-176 and P273-274 Nobuo Izumiya, Tetsuo Kato, Toshihiko Aoyagi, Michinori Waki, Basics and Experiments of Peptide Synthesis: Maruzen Co., Ltd., 1985, P38 Naohisa Ogo et. Al., Bioorganic & Medicinal Chemistry, 17 (4), 3921-3924 (2007) Sasse A., et. Al., Bioorganic & Medicinal Chemistry, 8 (5), 1139-1149 (2000) Dutta AK. Et. Al., Bioorganic & Medicinal Chemistry, 11 (17), 2337-2340 (2001) Shanklin JR Jr. et al., J. Med. Chem., 34 (10), 3011-3022 (1991)

  The present invention has been made under such circumstances, pigmentation due to ultraviolet exposure and the like, especially, abnormal pigmentation due to increased melanin production, more specifically, melanin abundance 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 the compound represented by the following general formula (1) and / or a pharmacologically acceptable salt thereof, and 2) a whitening component.

（１）
[式（１）中Aは、ジ又はトリ芳香族メチル基を表し、該芳香族は、無置換又は置換基を有するアリール基、及び無置換又は置換基を有する複素芳香族環よりなる群からそれぞれ独立に選ばれる。式（１）中Bは、Aとの結合部位が複素原子である、水素原子、水素原子若しくは炭素原子が複素原子により置換されていてもよい環状若しくは非環状の脂肪族炭化水素基、又は芳香族炭化水素基を表す。]

(1)
[In the formula (1) , A represents a di- or triaromatic methyl group, and the aromatic is selected from the group consisting of an unsubstituted or substituted aryl group and an unsubstituted or substituted heteroaromatic ring. Each is chosen independently. In formula (1), B represents a hydrogen atom, a hydrogen atom, or a cyclic or non-cyclic aliphatic hydrocarbon group in which the carbon atom may be substituted with a hetero atom , or an aromatic Represents a group hydrocarbon group. ]

<2>
The composition according to <1>, wherein in the general formula (1) , A is a di- or triarylmethyl group .

（２）

(2 )

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

（３）
[式（３）中、Xは、窒素原子又はNH基を表し、Ｒ ₁ は、水素原子又は、水素原子若しくは炭素原子が複素原子で置換されていてもよい炭素数３〜８の環状脂肪族炭化水素基を表し、前記の環状脂肪族炭化水素基の環は、Ｒ ₁ のもう一方の末端がＸに再び結合して形成される環も包含する。]

(3)
[In the formula (3) , X represents a nitrogen atom or an NH group, and R ₁ represents a hydrogen atom or a cyclic aliphatic group having 3 to 8 carbon atoms in which a hydrogen atom or a carbon atom may be substituted with a hetero atom. The ring of the cyclic aliphatic hydrocarbon group which represents a hydrocarbon group includes a ring formed by rebonding the other end of R ₁ to X. ]

<4> The compound represented by the general formula (1) is a compound represented by the following general formula (4) The composition according to <2>.

（４）
[式（４）中、Ｘは、酸素原子を表し、Ｒ ₂ は、水素原子又は水素原子若しくは炭素原子が複素原子に置換されていてもよい炭素数１〜８の脂肪族炭化水素基を表す。]

(4)
Wherein (4), X represents an oxygen atom, R ₂ represents a hydrogen atom or a hydrogen atom or aliphatic hydrocarbon group having 1 to 8 carbon atoms which may carbon atoms substituted by hetero atom . ]

<5> The compound represented by the general formula (1) is a compound represented by the following general formula (5), the skin external preparation as described in <2>.

（５）
[式（５）中、Ｘは、窒素原子を表し、Ｒ ₃ 及びＲ ₄ は、それぞれ独立に、水素原子、又は水素原子若しくは炭素原子が複素原子に置換されていてもよい炭素数１〜８の脂肪族炭化水素基を表す。]

(5)
[In Formula (5) , X represents a nitrogen atom, R < ₃ > and R < ₄ > are respectively independently C1- C8 in which the hydrogen atom or the hydrogen atom or the carbon atom may be substituted by the hetero atom. Represents an aliphatic hydrocarbon group . ]

<6> The compound represented by the general formula (1) is a compound represented by the following general formula (6) A composition according to <2>.

（６）
[式（６）中、Ｘは、窒素原子又はNH基を表し、Ｒ ₅ は、水素原子、又は水素原子若しくは炭素原子が複素原子で置換されていてもよい炭素数３〜８の芳香族炭化水素基を表し、前記の芳香族炭化水素基の環は、Ｒ ₅ のもう一方の末端がＸに再び結合して形成される環も包含する。]

(6)
[In the formula (6) , X represents a nitrogen atom or an NH group, and R ₅ represents a hydrogen atom, or an aromatic carbon atom having 3 to 8 carbon atoms in which the hydrogen atom or carbon atom may be substituted with a hetero atom. The ring of the aromatic hydrocarbon group which represents a hydrogen group includes a ring formed by bonding the other end of R ₅ to X again. ]

Compounds represented by <7> Formula (3) is 1 - (diphenylmethyl) pyrrolidine (Compound 9), 1- (triphenylmethyl) pyrrolidine (Compound 10), 1- (diphenylmethyl) piperidine (Compound 11) The composition as described in <3> containing 1 type, or 2 or more types chosen from 1- (triphenylmethyl) piperidine (compound 12 ) .

１−（ジフェニルメチル）イミダゾール（化合物１）

1- (diphenylmethyl) imidazole (Compound 1)

１−（トリフェニルメチル）イミダゾール（化合物２）、

1- (triphenylmethyl) imidazole (Compound 2),

２−[（ジフェニルメチル）オキシ]エタノール（化合物３）

2 - [(diphenylmethyl) oxy] ethanol (Compound 3)

２−[（トリフェニルメチル）オキシ]エタノール（化合物４）

2 - [(triphenylmethyl) oxy] ethanol (Compound 4)

２−[（ジフェニルメチル）アミノ]エタノール（化合物５）

2 - [(diphenylmethyl) amino] ethanol (Compound 5)

２−[（トリフェニルメチル）アミノ]エタノール（化合物６）

2 - [(triphenylmethyl) amino] ethanol (Compound 6)

２−[（ジフェニルメチル）オキシ]エチルアミン（化合物７）

2-[(Diphenylmethyl) oxy] ethylamine (Compound 7)

２−[（トリフェニルメチル）オキシ]エチルアミン（化合物８）

2-[(Triphenylmethyl) oxy] ethylamine (Compound 8)

１−（ジフェニルメチル）ピロリジン（化合物９）

1- (Diphenylmethyl) pyrrolidine (Compound 9)

１−（トリフェニルメチル）ピロリジン（化合物１０）

1- (Triphenylmethyl) pyrrolidine (Compound 10)

１−（ジフェニルメチル）ピペリジン（化合物１１）

1- (Diphenylmethyl) piperidine (Compound 11)

１−（トリフェニルメチル）ピペリジン（化合物１２）

1- (Triphenylmethyl) piperidine (Compound 12)

<8> The compound represented by the general formula (4) is 2-[(diphenylmethyl) oxy] ethanol (compound 3), 2-[(triphenylmethyl) oxy] ethanol (compound 4), 2- [ The compound according to <4>, comprising one or more selected from the group consisting of (diphenylmethyl) oxy] ethylamine (compound 7) and 2-[(triphenylmethyl) oxy] ethylamine (compound 8). Composition.
<9> The compound represented by the general formula (5) is 2-[(diphenylmethyl) amino] ethanol (compound 5) and 2-[(triphenylmethyl) amino] ethanol (compound 6).
The composition according to <5>, comprising one or two selected from the group consisting of:
<10> One compound selected from the group consisting of 1- (diphenylmethyl) imidazole (compound 1) and 1- (triphenylmethyl) imidazole (compound 2), wherein the compound represented by the general formula (6) Or the composition as described in <6> containing 2 types.
<11> 0.001% by mass to 10% by mass of the compound represented by the general formula (1) and / or a pharmacologically acceptable salt thereof with respect to the total amount of the composition, The composition according to any one of <1> to <10>.
<12> 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 composition according to any one of <1> to <11>.
<13> The melanin production inhibitor includes 4-alkylresorcinol and salts thereof, ascorbic acid derivatives and salts thereof, hydroquinone derivatives and salts thereof, tranexamic acid derivatives and derivatives thereof, vitamin E derivatives and salts thereof, and pantethein-S-. <12> The composition according to <12>, comprising at least one selected from sulfonic acids and salts thereof.
<14> The composition according to <12>, wherein the α-MSH inhibitor includes a plant extract obtained from a legume Clara genus Clara.
<15> The dendrite elongation inhibitor for melanocytes is at least 1 selected from methylophiopogononone B, sophoraflavanone A, a plant extract obtained from Asteraceae yarrow, and a plant extract obtained from Liliaceae. The composition according to <12>, comprising a seed.
<16> The proton pump inhibitor is a plant extract obtained from Lamiaceae genus Thymus, plant extract obtained from Leguminosae Clara, plant extract obtained from Ginger ginger ginger, Cytoaceae ginger From a plant extract obtained from the cucurbitaceae genus Hachima, a plant extract obtained from the genus Hydrangea hydrangea Achacha, a plant extract obtained from the pine fungus matsuhodo nuclei, from the leguminous genus kihagi <12> The composition according to <12>, comprising at least one selected from a plant extract obtained and a plant extract obtained from a leguminous genus Spodoptera.
<17> The composition according to any one of <1> to <16>, wherein the whitening component is contained in an amount of 0.000001% by mass to 15% by mass with respect to the total amount of the composition.
<18> The composition according to any one of <1> to <17>, which is an external preparation for skin.
<19> The composition according to any one of <1> to <18>, which is a cosmetic.
<20> The composition according to any one of <1> to <19>, which is for whitening.
<21> The composition according to any one of <1> to <20>, which is used for prevention or improvement of pigmentation due to ultraviolet exposure.
<22> The composition according to any one of <1> to <21>, wherein the composition is for prevention or improvement of pigmentation abnormality involving cell inactivation of keratinocytes caused by melanin overtransport. .
<23>
<18> The composition according to <18>, wherein the external preparation for skin is in the form of an oil-in-water emulsifier.

According to the present invention, pigmentation due to exposure to ultraviolet rays, particularly, abnormal pigmentation due to increased melanin production, and more specifically, a skin external preparation suitable for a person having a large amount of melanin in the collected horny layer cells, etc. The composition of can be provided.

<Compounds represented by the general formula (1) of the present invention and pharmacologically acceptable salts thereof>
The composition of the present invention comprises 1) the compound represented by the general formula (1) and / or a pharmacologically acceptable salt thereof, and 2) a whitening component. The compound represented by the general formula (1) of the present invention and / or a pharmacologically acceptable salt thereof is a whitening component described later, specifically, a melanin production inhibitor, an α-MSH inhibitor, It has the effect | action which enhances a whitening effect by making it contain in a composition with the 1 type, or 2 or more types of whitening component selected from the group which consists of a dendritic extension inhibitor of a melanocyte, and a proton pump inhibitor. The action of enhancing the whitening effect in the present invention specifically refers to an action of enhancing the prevention or improvement effect on pigmentation due to ultraviolet exposure or the like, and more preferably, to keratinocytes due to excessive and / or chronic enhancement of melanin production. It means an action to enhance the prevention or improvement effect on pigmentation accompanied by rough skin such as incurable blemishes or dullness caused by excessive transport of melanin, accumulation and discharge delay, and delamination. The compound represented by the general formula (1) of the present invention and / or a pharmacologically acceptable salt thereof may be a component that enhances the whitening effect by being included in the composition together with the whitening component described later. It can be applied without any particular limitation.

In skin where normal pigmentation occurs due to stimulation such as exposure to ultraviolet rays, melanin production is increased in melanocytes. Furthermore, when excessive stimulation is applied to the skin, excessive or chronic increase in melanin production, and further phenomena such as excessive transport of melanin to keratinocytes, accumulation and delayed discharge occur, and keratinocyte cell function is impaired. activation, Turn-down <br/> is bad over di delay such Oh over bar given, finally, hard heal spots, dullness, skin symptoms such as pigmentation with rough skin symptoms such as layer peeling Deterioration will be observed. In those people who have worsened skin symptoms due to pigmentation, which is associated with decreased cell function of keratinocytes, when the stratum corneum is prepared, the appearance rate of nucleated cells is higher than the average, and the skin Skin symptoms such as delamination of the skin are observed. 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.

Stated here about the compound represented by the general formula (1), wherein, A is a complex of the aromatics with ants Lumpur group and / or an unsubstituted or substituted radical having an unsubstituted or substituted group Represents a di- or tri-aromatic methyl group independently selected from the group consisting of aromatic rings, and B is a hetero atom at the bonding site to A, a hydrogen atom, a hydrogen atom or a carbon atom is substituted by a hetero atom Represents a cyclic or acyclic aliphatic or aromatic hydrocarbon group which may be present . Before Symbol A represents an ant Lumpur group and / or unsubstituted or di or tri aromatic methyl groups each independently selected from the group consisting of heteroaromatic ring having a substituent having a substituted or unsubstituted group, wherein As a specific example relates to heteroaromatic ring having ants Lumpur group and / or an unsubstituted or substituted radical having an unsubstituted or substituted group in a, a phenyl group, a naphthyl group, a biphenyl group, a pyridyl group, a furyl group, a thienyl group, a thiazolyl group, imidazole group, methylphenyl group, ethylphenyl group, propylphenyl group, methoxyphenyl group, ethoxyphenyl group, propyloxyphenyl group, hydroxyphenyl group, aminophenyl group, N- methylamino-phenyl group, N-ethylaminophenyl group, N-propylaminophenyl group, N, N-dimethylaminophenyl group, N, N-diethyla Nophenyl group, N, N-dipropylaminophenyl group, fluorophenyl group, difluorophenyl group, trifluoromethylphenyl group, chlorophenyl group, bromophenyl group, methylpyridyl group, ethylpyridyl group, propylpyridyl group, methoxypyridyl group, Ethoxypyridyl group, propyloxypyridyl group, hydroxypyridyl group, aminopyridyl group, N-methylaminopyridyl group, N-ethylaminopyridyl group, N-propylaminopyridyl group, N, N-dimethylaminopyridyl group, N, N -Diethylaminopyridyl group, N, N-dipropylaminopyridyl group, fluoropyridyl group, difluoropyridyl group, trifluoromethylpyridyl group, chloropyridyl group, bromopyridyl group, methylnaphthyl group, ethylnaphthyl group, propylnaphthyl group, methoxy Naphthyl group, ethoxynaphthyl group, propyloxynaphthyl group, hydroxynaphthyl group, aminonaphthyl group, N-methylaminonaphthyl group, N-ethylaminonaphthyl group, N-propylaminonaphthyl group, N, N-dimethylaminonaphthyl group, N, N-diethylamino-naphthyl group, N, N-dipropylamino naphthyl group, fluoro naphthyl group, difluoromethyl naphthyl group, a trifluoromethyl naphthyl group, chloronaphthyl group, bromonaphthyl group, imidazolinium group, methyl imidazolinium Le group , ethyl imidazolinium group, propyl imidazolium group, methoxy imidazolidone group, ethoxy imidazolinium group, propyloxy imidazolinium group, hydroxy imidazolinium group, amino imidazolinium Le group, N- methylamino imidazolinium Le group, N- ethylamino imidazolinium Le group, N- propylidene Amino imidazolinium group, N, N-dimethylamino imidazolinium group, N, N-diethylamino imidazolinium group, N, N-dipropylamino imidazolinium group, fluoro imidazolinium group, difluoromethyl imidazolinium Le group , trifluoromethyl imidazolinium group, chloro imidazolinium group, bromo imidazolinium Le group and the like can be preferably exemplified, more preferably a phenyl group, methylphenyl group, methoxyphenyl group, naphthyl group, biphenyl group suitably It can be illustrated.
B represents a cyclic atom or a non-cyclic aliphatic or aromatic hydrocarbon group in which the bonding site to A is a hetero atom, a hydrogen atom, a hydrogen atom or a carbon atom optionally substituted with a hetero atom; For example, a mono- or di-substituted amino group, a hydrogen atom or a carbon having a cyclic aliphatic hydrocarbon group having 3 to 8 carbon atoms in which a hydroxyl group, an amino group, a hydrogen atom or a carbon atom may be substituted by a hetero atom An alkyloxy group having a cyclic aliphatic hydrocarbon group having 3 to 8 carbon atoms in which an atom may be substituted by a hetero atom, a hydrogen atom or a carbon atom having 1 to 8 carbon atoms in which the carbon atom may be substituted by a hetero atom, More preferably, it is a mono- or di-substituted amino group having a C 1-4 aliphatic hydrocarbon group, a hydrogen atom or a carbon atom that may be substituted with a hetero atom, and more preferably carbon. A mono- or di-substituted amino group having an alkyloxy group having a C 1-4 aliphatic hydrocarbon group, a hydrogen atom or a C 3-8 aromatic hydrocarbon group in which a carbon atom may be substituted with a hetero atom Represents an alkyloxy group having an aromatic hydrocarbon group having 3 to 8 carbon atoms in which a hydrogen atom or a carbon atom may be substituted with a hetero atom. The B is a hydrogen atom or a disubstituted amino group having a cyclic aliphatic hydrocarbon group having 3 to 8 carbon atoms in which a carbon atom may be substituted with a heteroatom, or a hydrogen atom or a carbon atom is a heteroatom. In the case of representing a disubstituted amino group having an aromatic hydrocarbon group having 3 to 8 carbon atoms which may be substituted by, bonding of A and B to a ring of a cyclic aliphatic hydrocarbon group or an aromatic group The structure including the hetero atom of the site is also included.
Among the compounds represented by the general formula (1), more preferable examples include the compounds represented by the general formula (2) and / or pharmacologically acceptable salts thereof. More preferable examples include compounds represented by the general formulas (3) to (6) and / or pharmacologically acceptable salts thereof. Specific examples of the compounds represented by the general formula (1) that are not included in the compounds represented by the general formulas (2) to (6) include 1- [phenyl (pyridyl) methyl. ] imidazole, 1- (dipyridyl-methyl) imidazole, 1- [diphenyl (pyridyl) methyl] imidazole, 1 - [(dipyridyl) phenylmethyl] imidazole, 1- (tri-pyridylmethyl) imidazo over Le, 2 - {[phenyl (pyridyl) methyl] oxy} ethanol, 2 - [(dipyridyl) oxy] ethanol, 2 - {[diphenyl (pyridyl) methyl] oxy} ethanol, 2- { [dipyridyl (phenyl) methyl] oxy} ethanol, 2 - [(tri-pyridyl) oxy] ethanol, 2 - {[phenyl (pyridyl) methyl] amino} ethanol, 2 - [(dipyridyl methyl) Amino] eta Bruno Lumpur, 2 - {[diphenyl (pyridyl) methyl] amino} ethanol, 2 - {[dipyridyl (phenyl) methyl] amino} ethanol, 2 - [(tri-pyridyl methyl) amino] ethanol, 2-{[phenyl (pyridyl) methyl] oxy} ethylamine, 2-[(dipyridylmethyl) oxy] ethylamine, 2-{[diphenyl (pyridyl) methyl] oxy} ethylamine, 2-{[dipyridyl (phenyl) methyl] oxy } Ethylamine, 2-[(tripyridylmethyl) oxy] ethylamine, 1- [phenyl (pyridyl) methyl] pyrrolidine, 1-dipyridylmethylpyrrolidine, 1- [diphenyl (pyridyl) methyl] pyrrolidine, 1-[(dipyridyl) phenyl Methyl] pyrrolidine, 1- (tripyridylmethyl) pyrrolidine, 1- [phenyl (pyridyl) methyl] piperidine, 1-di Pyridylmethylpiperidine, 1- [diphenyl (pyridyl) methyl] piperidine, 1-[(dipyridyl) phenylmethyl] piperidine, 1- (tripyridylmethyl) piperidine and / or their pharmacologically acceptable salts are preferred. Can be illustrated. Among the compounds represented by the general formula (1), if specifically exemplified preferred, 1- (diphenylmethyl) imidazole (Compound 1), 1- (triphenylmethyl) imidazole (compound 2), 2 - [(diphenylmethyl) oxy] ethanol (compound 3), 2 - [(triphenylmethyl) oxy] ethanol (compound 4), 2 - [(diphenylmethyl) amino] ethanol Lumpur (compound 5), 2 - [(triphenylmethyl) amino] ethanol (compound 6), 2 - [(diphenylmethyl) oxy] ethylamine (compound 7), 2 - [(triphenylmethyl) oxy] Ethylamine (Compound 8), 1- (Diphenylmethyl) pyrrolidine (Compound 9), 1- (Triphenylmethyl) pyrrolidine (Compound 10), 1- (Diphenylmethyl) piperidine (Compound 1) ), 1- (triphenylmethyl) piperidine (Compound 12) and / or their pharmacologically acceptable salts are suitably be exemplified. By including such a compound in the composition together with the whitening component described later,
It enhances the effect of the whitening component and exhibits an excellent whitening effect. Further, such compounds and / or pharmacologically acceptable salts thereof have excellent safety and stability, and can be contained stably and safely in the composition.

Stated here about the compound represented by the general formula (2), wherein, A is di- or triaryl the aryl is selected independently from the group consisting of ants Lumpur group having unsubstituted or substituted group over Rumechiru represents a group, B is the binding site of a is a hetero atom, a hydrogen atom, a hydrogen atom or a carbon atom of the cyclic ring or acyclic be substituted with a hetero atom aliphatic or aromatic hydrocarbon Represents a group. Related to Ali Lumpur group having unsubstituted or substituted group in the A, to name preferred compounds are specific examples, a phenyl group, a naphthyl group, a biphenyl group, methylphenyl group, ethylphenyl group, propylphenyl group, a methoxyphenyl group , Ethoxyphenyl group, propyloxyphenyl group, hydroxyphenyl group, aminophenyl group, N-methylaminophenyl group, N-ethylaminophenyl group, N-propylaminophenyl group, N, N-dimethylaminophenyl group, N, N-diethylaminophenyl group, N, N-dipropylaminophenyl group, fluorophenyl group, difluorophenyl group, trifluoromethylphenyl group, chlorophenyl group, bromophenyl group, methylnaphthyl group, ethylnaphthyl group, propylnaphthyl group, methoxy Naphthyl group, ethoxynaphthyl group Propyloxynaphthyl group, hydroxynaphthyl group, aminonaphthyl group, N-methylaminonaphthyl group, N-ethylaminonaphthyl group, N-propylaminonaphthyl group, N, N-dimethylaminonaphthyl group, N, N-diethylaminonaphthyl Group, N, N-dipropylaminonaphthyl group, fluoronaphthyl group, difluoronaphthyl group, trifluoromethylnaphthyl group, chloronaphthyl group, bromonaphthyl group and the like can be suitably exemplified, more preferably phenyl group, methylphenyl group A methoxyphenyl group and a naphthyl group can be preferably exemplified. B represents a cyclic atom or a non-cyclic aliphatic or aromatic hydrocarbon group in which the bonding site to A is a hetero atom, a hydrogen atom, a hydrogen atom or a carbon atom optionally substituted with a hetero atom; For example, a mono- or di-substituted amino group, a hydrogen atom or a carbon having a cyclic aliphatic hydrocarbon group having 3 to 8 carbon atoms in which a hydroxyl group, an amino group, a hydrogen atom or a carbon atom may be substituted by a hetero atom An alkyloxy group having a cyclic aliphatic hydrocarbon group having 3 to 8 carbon atoms in which an atom may be substituted by a hetero atom, a hydrogen atom or a carbon atom having 1 to 8 carbon atoms in which the carbon atom may be substituted by a hetero atom, More preferably, it is a mono- or di-substituted amino group having a C 1-4 aliphatic hydrocarbon group, a hydrogen atom or a carbon atom that may be substituted with a hetero atom, and more preferably carbon. A mono- or di-substituted amino group having an alkyloxy group having a C 1-4 aliphatic hydrocarbon group, a hydrogen atom or a C 3-8 aromatic hydrocarbon group in which a carbon atom may be substituted with a hetero atom Represents an alkyloxy group having an aromatic hydrocarbon group having 3 to 8 carbon atoms in which a hydrogen atom or a carbon atom may be substituted with a hetero atom. The B is a hydrogen atom or a disubstituted amino group having a cyclic aliphatic hydrocarbon group having 3 to 8 carbon atoms in which a carbon atom may be substituted with a heteroatom, or a hydrogen atom or a carbon atom is a heteroatom. In the case of representing a disubstituted amino group having an aromatic hydrocarbon group having 3 to 8 carbon atoms which may be substituted by, bonding of A and B to a ring of a cyclic aliphatic hydrocarbon group or an aromatic group The structure including the hetero atom of the site is also included. Of the compounds represented by the general formula (2), more preferred are the compounds represented by the general formulas (3) to (6) and / or pharmacologically acceptable salts thereof. illustration can, if specific examples of the more preferred compound, 1- (diphenylmethyl) imidazole (compound 1), 1- (triphenylmethyl) imidazole (compound 2), 2 - [(diphenylmethyl ) oxy] ethanol (compound 3), 2 - [(triphenylmethyl) oxy] ethanol (compound 4), 2 - [(diphenylmethyl) amino] ethanol (compound 5), 2 - [( triphenylmethyl) amino] ethanol (compound 6), 2 - [(diphenylmethyl) oxy] ethylamine (compound 7), 2 - [(triphenylmethyl) oxy] ethylamine (compound 8), l- (diphenylmethyl main L) pyrrolidine (compound 9), 1- (triphenylmethyl) pyrrolidine (compound 10), 1- (diphenylmethyl) piperidine (compound 11), 1- (triphenylmethyl) piperidine (compound 12) and / or their Preferred examples include pharmacologically acceptable salts. When such a compound is contained in the composition together with the whitening component described later, the effect of the whitening component is enhanced and an excellent whitening action is exhibited. Further, such compounds and / or pharmacologically acceptable salts thereof have excellent safety and stability, and can be contained stably and safely in the composition.

Stated here with the compound represented by the general formula (3), wherein, A is di- or triaryl the aryl is selected independently from the group consisting of ants Lumpur group having unsubstituted or substituted group represents an over Rumechiru group, X represents a nitrogen atom or an NH group, R ₁ is a hydrogen atom, a hydrogen atom or a cyclic aliphatic hydrocarbon of carbon atoms carbon atoms which may be substituted with a hetero atom 3-8 The ring of the above cyclic aliphatic hydrocarbon group also includes a ring formed by bonding the other end of R ₁ to X again. Related to Ali Lumpur group having unsubstituted or substituted group in the A, if specifically exemplified preferred, a phenyl group, a naphthyl group, a biphenyl group, methylphenyl group, ethylphenyl group, propylphenyl group, methoxyphenyl Group, ethoxyphenyl group, propyloxyphenyl group, hydroxyphenyl group, aminophenyl group, N-methylaminophenyl group, N-ethylaminophenyl group, N-propylaminophenyl group, N, N-dimethylaminophenyl group, N , N-diethylaminophenyl group, N, N-dipropylaminophenyl group, fluorophenyl group, difluorophenyl group, trifluoromethylphenyl group, chlorophenyl group, bromophenyl group, methylnaphthyl group, ethylnaphthyl group, propylnaphthyl group, Methoxynaphthyl group, ethoxynaphthyl Group, propyloxynaphthyl group, hydroxynaphthyl group, aminonaphthyl group, N-methylaminonaphthyl group, N-ethylaminonaphthyl group, N-propylaminonaphthyl group, N, N-dimethylaminonaphthyl group, N, N-diethylamino A naphthyl group, an N, N-dipropylaminonaphthyl group, a fluoronaphthyl group, a difluoronaphthyl group, a trifluoromethylnaphthyl group, a chloronaphthyl group, a bromonaphthyl group, and the like can be preferably exemplified, and more preferably, a phenyl group, methylphenyl A group, a methoxyphenyl group, a naphthyl group and the like can be preferably exemplified. X represents a nitrogen atom or an NH group.
R ₁ represents a C 3-8 cyclic aliphatic hydrocarbon group in which a hydrogen atom, a hydrogen atom, or a carbon atom may be substituted with a hetero atom, and the ring of the cyclic aliphatic hydrocarbon group is R Also included is a ring formed by bonding the other end of ₁ to X again. Specific examples of preferred R ₁ include N-cyclopropyl group, N-cyclobutyl group, N-cyclopentyl group, N-cyclohexyl group, N-cycloheptyl group, N-cyclooctyl group, and succinimide group. Can be suitably exemplified. Examples of the substituent having a ring structure in which the ring of the cyclic aliphatic hydrocarbon group is formed by rebonding the other end of R ₁ to X (including the X moiety) include a pyrrolidino group, methylpyrrolidino Group, ethylpyrrolidino group, propylpyrrolidino group, methoxypyrrolidino group, ethoxypyrrolidino group, propyloxypyrrolidino group, hydroxypyrrolidino group, aminopyrrolidino group, N-methylpyrrolidino group, N-ethylpyrrolidino group Group, N-propylpyrrolidino group, N, N-dimethylpyrrolidino group, N, N-diethylpyrrolidino group, N, N-dipropylpyrrolidino group, fluoropyrrolidino group, difluoropyrrolidino group, trifluoromethyl pyrrolidino group, chloro pyrrolidinopyridine group, piperidyl amino group, Mechirupiperiji amino group, Echirupiperiji amino group, a propyl piperidinocarbonyl group, Metokishipiperiji Group, Etokishipiperiji amino group, propyloxy piperidinocarbonyl group, hydroxypiperidino group, Aminopiperiji amino group, N- Mechirupiperiji amino group, N- Echirupiperiji amino group, N- propyl piperidinocarbonyl group, N, N- Jimechirupiperiji cyano group , N, N-Jiechirupiperiji amino group, N, N-dipropyl-piperidinophenyl group, Furuoropiperiji amino group, difluoromethyl piperidinocarbonyl group, trifluoromethyl piperidinophenyl group, Kuroropiperiji amino group, piperazino group, a methylpiperazino group, ethylpiperazino group Propylpiperazino group, methoxypiperazino group, ethoxypiperazino group, propyloxypiperazino group, hydroxypiperazino group, aminopiperazino group, N-methylpiperazino group, N-ethylpiperazino group, N-propylpiperazi group Group, N, N-dimethylpiperazino group, N, N-diethylpiperazino group N, N-dipropylpiperazino group, fluoropiperazino group, difluoropiperazino group, trifluoromethylpiperazino group, chloropiperazino group, morpholino group, methylmorpholino group, ethylmorpholino group, propylmorpholino group, methoxy Morpholino group, ethoxymorpholino group, propyloxymorpholino group, hydroxymorpholino group, aminomorpholino group, N-methylmorpholino group, N-ethylmorpholino group, N-propylmorpholino group, N, N-dimethylmorpholino group, N, N- diethyl morpholino group, N, N-dipropyl morpholino group, fluoro morpholino group, difluoromethyl morpholino group, trifluoromethyl morpholino group, Kuroromoruhorino group and the like can be preferably exemplified, and more preferably, pyrrolidine amino group, piperidyl amino group, piperazine Roh group, a morpholino group, and the like are good Can exemplified, more preferably, piperidino group suitably be exemplified. Specific examples of preferable compounds among the compounds represented by the general formula (3) include N- (diphenylmethyl) succinimide, N-[(methylphenyl) phenylmethyl] succinimide, and N- [bis (methyl Phenyl) methyl] succinimide, N-[(ethylphenyl) phenylmethyl] succinimide, N- [bis (ethylphenyl) methyl] succinimide, N-[(methoxyphenyl) phenylmethyl] succinimide, N- [bis (methoxyphenyl) Methyl] succinimide, N-[(ethoxyphenyl) phenylmethyl] succinimide, N- [bis (ethoxyphenyl) methyl] succinimide, N-[(fluorophenyl) phenylmethyl] succinimide, N- [bis (fluorophenyl) methyl] Succinimide, N- (triphenylmethyl) succinimide, N- [ Diphenyl (methylphenyl) methyl] succinimide, N- [bis (methylphenyl) phenylmethyl] succinimide, N- [tris (methylphenyl) methyl] succinimide, N- [diphenyl (ethylphenyl) methyl] succinimide, N- [bis (Ethylphenyl) phenylmethyl] succinimide, N- [tris (ethylphenyl) methyl] succinimide, N- [diphenyl (methoxyphenyl) methyl] succinimide, N- [bis (methoxyphenyl) phenylmethyl] succinimide, N- [tris (Methoxyphenyl) methyl] succinimide, N- [diphenyl (ethoxyphenyl) methyl] succinimide, N- [bis (ethoxyphenyl) phenylmethyl] succinimide, N- [tris (ethoxyphenyl) methyl] succinimide, N- [diphenyl ( F Olophenyl) methyl] succinimide, N- [bis (fluorophenyl) phenylmethyl] succinimide, N- [tris (fluorophenyl) methyl] succinimide, 1- (diphenylmethyl) pyrrolidine (compound 9), 1-[(methylphenyl) Phenylmethyl] pyrrolidine, 1- [bis (methylphenyl) methyl] pyrrolidine, 1-[(ethylphenyl) phenylmethyl] pyrrolidine, 1- [bis (ethylphenyl) methyl] pyrrolidine, 1-[(methoxyphenyl) phenylmethyl ] Pyrrolidine, 1- [bis (methoxyphenyl) methyl] pyrrolidine, 1-[(ethylphenyl) phenylmethyl] pyrrolidine, 1- [bis (ethylphenyl) methyl] pyrrolidine, 1-[(hydroxyphenyl) phenylmethyl] pyrrolidine , 1- [bis (hydroxyphenyl) methyl Ru] pyrrolidine, 1-[(aminophenyl) phenylmethyl] pyrrolidine, 1- [bis (aminophenyl) methyl] pyrrolidine, 1-[(fluorophenyl) phenylmethyl] pyrrolidine, 1- [bis (fluorophenyl) methyl] Pyrrolidine, 1-[(chlorophenyl) phenylmethyl] pyrrolidine, 1- [bis (chlorophenyl) methyl] pyrrolidine, 1- (triphenylmethyl) pyrrolidine (compound 10), 1- [diphenyl (methylphenyl) methyl] pyrrolidine, 1 -[Bis (methylphenyl) phenylmethyl] pyrrolidine, 1- [tris (methylphenyl) methyl] pyrrolidine, 1- [diphenyl (ethylphenyl) methyl] pyrrolidine, 1- [bis (ethylphenyl) phenylmethyl] pyrrolidine, 1 -[Tris (ethylphenyl) methyl] pyrrolidine, 1- [di Phenyl (methoxyphenyl) methyl] pyrrolidine, 1- [bis (methoxyphenyl) phenylmethyl] pyrrolidine, 1- [tris (methoxyphenyl) methyl] pyrrolidine, 1- [diphenyl (ethoxyphenyl) methyl] pyrrolidine, 1- [bis (Ethoxyphenyl) phenylmethyl] pyrrolidine, 1- [tris (ethoxyphenyl) methyl] pyrrolidine, 1- [diphenyl (hydroxyphenyl) methyl] pyrrolidine, 1- [bis (hydroxyphenyl) phenylmethyl] pyrrolidine, 1- [tris (Hydroxyphenyl) methyl] pyrrolidine, 1-[(aminophenyl) diphenylmethyl] pyrrolidine, 1- [bis (aminophenyl) phenylmethyl] pyrrolidine, 1- [tris (aminophenyl) methyl] pyrrolidine, 1- [diphenyl ( Fluorophenyl) methyl] Loridine, 1- [bis (fluorophenyl) phenylmethyl] pyrrolidine, 1- [tris (fluorophenyl) methyl] pyrrolidine, 1- (diphenylmethyl) piperidine (compound 11), 1-[(methylphenyl) phenylmethyl] pi Peridine, 1- [bis (methylphenyl) methyl] piperidine, 1-[(ethylphenyl) phenylmethyl] piperidine, 1- [bis (ethylphenyl) methyl] piperidine, 1-[(methoxy Phenyl) phenylmethyl] piperidine, 1- [bis (methoxyphenyl) methyl] piperidine, 1-[(ethylphenyl) phenylmethyl] piperidine, 1- [bis (ethylphenyl) methyl] piperidine 1-[(hydroxyphenyl) phenylmethyl] piperidine, 1- [bis (hydroxyphenyl) methyl] piperidine, 1-[(aminophenyl) Nyl) phenylmethyl] piperidine, 1- [bis (aminophenyl) methyl] piperidine, 1-[(fluorophenyl) phenylmethyl] piperidine, 1- [bis (fluorophenyl) methyl] piperidine, 1-[(chlorophenyl) phenyl Methyl] piperidine, 1- [bis (chlorophenyl) methyl] piperidine, 1- (triphenylmethyl) piperidine (compound 12), 1- [diphenyl (methylphenyl) methyl] piperidine, 1- [bis (methylphenyl) phenylmethyl ] Piperidine, 1- [tris (methylphenyl) methyl] piperidine, 1- [diphenyl (ethylphenyl) methyl] piperidine, 1- [bis (ethylphenyl) phenylmethyl] piperidine, 1- [tris (ethylphenyl) methyl] Piperidine, 1- [diphenyl (methoxyphenyl) methyl L] piperidine, 1- [bis (methoxyphenyl) phenylmethyl] piperidine, 1- [tris (methoxyphenyl) methyl] piperidine, 1- [diphenyl (ethoxyphenyl) methyl] piperidine, 1- [bis (ethoxyphenyl) phenyl Methyl] piperidine, 1- [tris (ethoxyphenyl) methyl] piperidine, 1- [diphenyl (hydroxyphenyl) methyl] piperidine, 1- [bis (hydroxyphenyl) phenylmethyl] piperidine, 1- [tris (hydroxyphenyl) methyl ] Piperidine, 1-[(aminophenyl) diphenylmethyl] piperidine, 1- [bis (aminophenyl) phenylmethyl] piperidine, 1- [tris (aminophenyl) methyl] piperidine, 1- [diphenyl (fluorophenyl) methyl] Piperidine, 1- [bis (fluoro Enyl) phenylmethyl] piperidine, 1- [tris (fluorophenyl) methyl] piperidine, 1- (diphenylmethyl) morpholine, 1-[(methylphenyl) phenylmethyl] morpholine, 1- [bis (methylphenyl) methyl] morpholine 1-[(ethylphenyl) phenylmethyl] morpholine, 1- [bis (ethylphenyl) methyl] morpholine, 1-[(methoxyphenyl) phenylmethyl] morpholine, 1- [bis (methoxyphenyl) methyl] morpholine, -[(Ethylphenyl) phenylmethyl] morpholine, 1- [bis (ethylphenyl) methyl] morpholine, 1-[(hydroxyphenyl) phenylmethyl] morpholine, 1- [bis (hydroxyphenyl) methyl] morpholine, 1- [ (Aminophenyl) phenylmethyl] morpholine, 1- [bis ( Minophenyl) methyl] morpholine, 1-[(fluorophenyl) phenylmethyl] morpholine, 1- [bis (fluorophenyl) methyl] morpholine, 1-[(chlorophenyl) phenylmethyl] morpholine, 1- [bis (chlorophenyl) methyl] Morpholine, 1- (triphenylmethyl) morpholine, 1- [diphenyl (methylphenyl) methyl] morpholine, 1- [bis (methylphenyl) phenylmethyl] morpholine, 1- [tris (methylphenyl) methyl] morpholine, [Diphenyl (ethylphenyl) methyl] morpholine, 1- [bis (ethylphenyl) phenylmethyl] morpholine, 1- [tris (ethylphenyl) methyl] morpholine, 1- [diphenyl (methoxyphenyl) methyl] morpholine, 1- [ Bis (methoxyphenyl) phenylmethyl] Ruphorin, 1- [tris (methoxyphenyl) methyl] morpholine, 1- [diphenyl (ethoxyphenyl) methyl] morpholine, 1- [bis (ethoxyphenyl) phenylmethyl] morpholine, 1- [tris (ethoxyphenyl) methyl] morpholine 1- [diphenyl (hydroxyphenyl) methyl] morpholine, 1- [bis (hydroxyphenyl) phenylmethyl] morpholine, 1- [tris (hydroxyphenyl) methyl] morpholine, 1-[(aminophenyl) diphenylmethyl] morpholine, 1- [bis (aminophenyl) phenylmethyl] morpholine, 1- [tris (aminophenyl) methyl] morpholine, 1- [diphenyl (fluorophenyl) methyl] morpholine, 1- [bis (fluorophenyl) phenylmethyl] morpholine, 1- [Tris (fluoroph Yl) methyl] morpholine and / or salts thereof pharmacologically acceptable can preferably exemplified,
More preferable examples include 1- (diphenylmethyl) pyrrolidine (compound 9), 1- (triphenylmethyl) pyrrolidine (compound 10), 1- (diphenylmethyl) piperidine (compound 11), 1- (triphenylmethyl) Preferred examples include piperidine (Compound 12) and / or pharmacologically acceptable salts thereof. When such a compound is contained in the composition together with the whitening component described later, the effect of the whitening component is enhanced and an excellent whitening action is exhibited. Further, such compounds and / or pharmacologically acceptable salts thereof have excellent safety and stability, and can be contained stably and safely in the composition.

Stated here with the compound represented by general formula (4), wherein, A is di- or triaryl the aryl is selected independently from the group consisting of ants Lumpur group having unsubstituted or substituted group represents Lumpur group, X represents an oxygen atom, R ₂ represents a hydrogen atom, a hydrogen atom or an aliphatic hydrocarbon group having 1 to 8 carbon atoms which may be substituted carbon atom by a heteroatom. Related to Ali Lumpur group having unsubstituted or substituted group in the A, if specifically exemplified preferred, a phenyl group, a naphthyl group, a biphenyl group, methylphenyl group, ethylphenyl group, propylphenyl group, methoxyphenyl Group, ethoxyphenyl group, propyloxyphenyl group, hydroxyphenyl group, aminophenyl group, N-methylaminophenyl group, N-ethylaminophenyl group, N-propylaminophenyl group, N, N-dimethylaminophenyl group, N , N-diethylaminophenyl group, N, N-dipropylaminophenyl group, fluorophenyl group, difluorophenyl group, trifluoromethylphenyl group, chlorophenyl group, bromophenyl group, methylnaphthyl group, ethylnaphthyl group, propylnaphthyl group, Methoxynaphthyl group, ethoxynaphthyl Group, propyloxynaphthyl group, hydroxynaphthyl group, aminonaphthyl group, N-methylaminonaphthyl group, N-ethylaminonaphthyl group, N-propylaminonaphthyl group, N, N-dimethylaminonaphthyl group, N, N-diethylamino A naphthyl group, an N, N-dipropylaminonaphthyl group, a fluoronaphthyl group, a difluoronaphthyl group, a trifluoromethylnaphthyl group, a chloronaphthyl group, a bromonaphthyl group, and the like can be suitably exemplified, and more preferably a phenyl group, a naphthyl group , Methylphenyl group, methoxyphenyl group and the like can be preferably exemplified. X represents an oxygen atom. R ₂ represents an aliphatic hydrocarbon group having 1 to 8 carbon atoms, more preferably 1 to 4 carbon atoms in which a hydrogen atom or a carbon atom may be substituted with a hetero atom. Hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, hydroxyheptyl, hydroxyoctyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl Group, methoxyhexyl group, methoxyheptyl group, methoxyoctyl group, dihydroxymethyl group, dihydroxyethyl group, dihydroxypropyl group, dihydroxybutyl group, dihydroxypentyl group, dihydroxyhexyl group, dihydroxyheptyl group, dihydroxyoctyl group, a Nomechiru group, aminoethyl group, aminopropyl group, aminobutyl group, aminopentyl group, an aminohexyl group, an amino heptyl group, an amino octyl be preferably exemplified, and more preferably, Hirokishiechiru group, aminoethyl group, methoxyethyl A group can be preferably exemplified. Among the compounds represented by the general formula (4), if Specific examples of the preferred compounds, 1- (diphenylmethyl oxy) methanol, 3- (diphenylmethyl oxy) propanol Lumpur, 4- (diphenyl methyloxy) butanol, 5- (diphenylmethyl oxy) pentanol Lumpur, 6- (diphenylmethyl oxy) hexanol Lumpur, 7- (diphenylmethyl oxy) Heputano Lumpur, 8- (diphenylmethyl oxy) octanol Lumpur 1- (triphenylmethyl oxy) methanol, 3- (triphenylmethyl oxy) propanol Lumpur, 4- (triphenylmethyl oxy) butanol, 5- (triphenylmethyl oxy) pentanol Lumpur, 6 - (triphenylmethyl oxy) hexanol Lumpur, 7- (triphenylmethyl oxy) Heputano Lumpur, 8- (triphenyl Methyloxy) octanol Lumpur, 1- (diphenylmethyl) methyl amine, 3- (diphenylmethyl) propyl amine amine, 4- (diphenylmethyl oxy) butylamine, 5- (diphenylmethyl oxy) pentylamine, 6- ( Diphenylmethyloxy) hexylamine, 7- (diphenylmethyloxy) heptylamine, 8- (diphenylmethyloxy) octylamine, 1- (triphenylmethyloxy) methylamine, 3- (triphenylmethyloxy) propylamine, 4 -(Triphenylmethyloxy) butylamine, 5- (triphenylmethyloxy) pentylamine, 6- (triphenylmethyloxy) hexylamine, 7- (triphenylmethyloxy) heptylamine, 8- (triphenylmethyloxy) ) Octylamine, 1- (diphenylmethyl amino) methanol, 3- (diphenylmethylamino) propanol Lumpur, 4- (diphenylmethyl amino) butanol, 5- (diphenylmethyl amino) pentanol Lumpur, 6- (diphenylmethylamino) hexanol Lumpur, 7- (diphenylmethyl amino) Heputano Lumpur, 8- (diphenylmethyl amino) octanol Lumpur, 1- (triphenylmethyl amino) methanol, 3- (triphenylmethyl amino ) propanol Lumpur, 4- (triphenylmethyl amino) butanol, 5- (triphenylmethyl amino) pentanol Lumpur, 6- (triphenylmethyl amino) hexanol Lumpur, 7- (triphenylmethyl amino) Heputano Lumpur, 8- (triphenylmethyl amino) octanol Lumpur, 2 - [(diphenylmethyl) Carboxymethyl] ethanol (Compound 3), 2 - [(methylphenyl) phenyl methyloxy] ethanol, 2- [bis (methylphenyl) methyl oxy] ethanol, 2 - [(ethylphenyl) phenylmethyloxy ] ethanol, 2 - [(bis (ethylphenyl) methyl oxy] ethanol, 2 - [(methoxyphenyl) phenyl methyloxy] ethanol, 2 - [(bis (methoxyphenyl) methyl oxy] ethanol over Le, 2 - [(ethoxy) phenylmethyl oxy] ethanol, 2 - [(bis (ethoxyphenyl) methyloxy] ethanol, 2 - [(hydroxyphenyl) phenyl methyloxy] ethanol, 2- [(bis (hydroxyphenyl) methyloxy] ethanol, 2 - [(amino) phenylmethyl oxy] ethanol, 2 - [(bis (Aminofeni Le) methyloxy] ethanol, 2 - [(fluorophenyl) phenylmethyl oxy] ethanol, 2 - [(bis (fluorophenyl) methyloxy] ethanol, 2 - [(triphenylmethyl) oxy] ethanol (compound 4) 2- [diphenyl (methyl phenyl) methyloxy] ethanol, 2- [bis (methylphenyl) phenyl methyloxy] ethanol, 2- [tris (methylphenyl) methyloxy] ethanol, 2- [diphenyl (ethyl phenyl) methyloxy] ethanol, 2- [bis (ethylphenyl) phenyl methyloxy] ethanol, 2- [tris (ethylphenyl) methyl oxy] ethanol, 2- [diphenyl (methoxyphenyl) methyloxy] ethanol, 2- [bis (methoxyphenyl) phenyl methyloxy] ethanol, 2- [DOO Scan (methoxyphenyl) methyloxy] ethanol, 2- [diphenyl (ethoxy) methyl oxy] ethanol, 2- [bis (ethoxy) phenylmethyl oxy] ethanol, 2- [tris (ethoxyphenyl ) methyloxy] ethanol, 2- [diphenyl (hydroxyphenyl) methyloxy] ethanol, 2- [bis (hydroxyphenyl) phenyl methyloxy] ethanol, 2- [tris (hydroxyphenyl) methyloxy] ethanol, 2 - [(aminophenyl) diphenylmethyl oxy] ethanol, 2- [bis (aminophenyl) phenyl methyloxy] ethanol, 2- [tris (aminophenyl) methyloxy] ethanol, 2- [diphenyl (fluorophenyl) methyloxy] ethanol, 2- [bis (fluorophenyl) off Sulfonyl methyloxy] ethanol, 2- [tris (fluorophenyl) methyloxy] ethanol, 2 - [(diphenylmethyl) oxy] ethylamine (Compound 7), 2 - [(methylphenyl) phenyl methyloxy] ethylamine 2- [bis (methylphenyl) methyloxy] ethylamine, 2-[(ethylphenyl) phenylmethyloxy] ethylamine, 2-[(bis (ethylphenyl) methyloxy] ethylamine, 2-[(methoxyphenyl) phenylmethyl Oxy] ethylamine, 2-[(bis (methoxyphenyl) methyloxy] ethylamine, 2-[(ethoxyphenyl) phenylmethyloxy] ethylamine, 2-[(bis (ethoxyphenyl) methyloxy] ethylamine, 2-[(hydroxy Phenyl) phenylmethyloxy] ethylamine, 2- [ Bis (hydroxyphenyl) methyloxy] ethylamine, 2-[(aminophenyl) phenylmethyloxy] ethylamine, 2-[(bis (aminophenyl) methyloxy] ethylamine, 2-[(fluorophenyl) phenylmethyloxyethylamine, 2 -[(Bis (fluorophenyl) methyloxy] ethylamine, 2-[(triphenylmethyl) oxy] ethylamine (compound 8), 2- [diphenyl (methylphenyl) methyloxy] ethylamine, 2- [bis (methylphenyl) Phenylmethyloxy] ethylamine, 2- [tris (methylphenyl) methyloxy] ethylamine, 2- [diphenyl (ethylphenyl) methyloxy] ethylamine, 2- [bis (ethylphenyl) phenylmethyloxy] ethylamine, 2- [tris (Ethylphenyl) Methyloxy] ethylamine, 2- [diphenyl (methoxyphenyl) methyloxy] ethylamine, 2- [bis (methoxyphenyl) phenylmethyloxy] ethylamine, 2- [tris (methoxyphenyl) methyloxy] ethylamine, 2- [diphenyl ( Ethoxyphenyl) methyloxy] ethylamine, 2- [bis (ethoxyphenyl) phenylmethyloxy] ethylamine, 2- [tris (ethoxyphenyl) methyloxy] ethylamine, 2- [diphenyl (hydroxyphenyl) methyloxy] ethylamine, 2- [Bis (hydroxyphenyl) phenylmethyloxy] ethylamine, 2- [tris (hydroxyphenyl) methyloxy] ethylamine, 2-[(aminophenyl) diphenylmethyloxy] ethylamine, 2- [bis (aminophenyl) phenyl Phenylmethyloxy] ethylamine, 2- [tris (aminophenyl) methyloxy] ethylamine, 2- [diphenyl (fluorophenyl) methyloxy] ethylamine, 2- [bis (fluorophenyl) phenylmethyloxy] ethylamine, 2- [tris (fluorophenyl) methyloxy] ethylamine and / or a pharmaceutically acceptable salt thereof pharmacologically can be preferably exemplified, and more preferably, 2 - [(diphenylmethyl) oxy] ethanol (compound 3), 2- [(triphenylmethyl) oxy] ethanol (compound 4), 2 - [(diphenylmethyl) oxy] ethylamine (compound 7), 2 - [(triphenylmethyl) oxy] ethylamine (compound 8) and / or their The pharmacologically acceptable salt of can be illustrated suitably. When such a compound is contained in the composition together with the whitening component described later, the effect of the whitening component is enhanced and an excellent whitening action is exhibited. Further, such compounds and / or pharmacologically acceptable salts thereof have excellent safety and stability, and can be contained stably and safely in the composition.

Stated here with the compound represented by general formula (5), wherein, A is di- or triaryl the aryl is selected independently from the group consisting of ants Lumpur group having unsubstituted or substituted group represents an over Rumechiru group, X represents a nitrogen atom, R ₃ and R ₄ are each independently a hydrogen atom, a hydrogen atom or a carbon atom which may have been a good C1-8 substituted heteroatom fat Represents a group hydrocarbon group . If Specific examples of the preferred relates to ant Lumpur group having unsubstituted or substituted group in the A, a phenyl group, a naphthyl group, a biphenyl group, methylphenyl group, ethylphenyl group, propylphenyl group, a methoxyphenyl group , Ethoxyphenyl group, propyloxyphenyl group, hydroxyphenyl group, aminophenyl group, N-methylaminophenyl group, N-ethylaminophenyl group, N-propylaminophenyl group, N, N-dimethylaminophenyl group, N, N-diethylaminophenyl group, N, N-dipropylaminophenyl group, fluorophenyl group, difluorophenyl group, trifluoromethylphenyl group, chlorophenyl group, bromophenyl group, methylnaphthyl group, ethylnaphthyl group, propylnaphthyl group, methoxy Naphthyl group, ethoxynaphthyl group Propyloxynaphthyl group, hydroxynaphthyl group, aminonaphthyl group, N-methylaminonaphthyl group, N-ethylaminonaphthyl group, N-propylaminonaphthyl group, N, N-dimethylaminonaphthyl group, N, N-diethylaminonaphthyl Group, N, N-dipropylaminonaphthyl group, fluoronaphthyl group, difluoronaphthyl group, trifluoromethylnaphthyl group, chloronaphthyl group, bromonaphthyl group and the like can be suitably exemplified, more preferably phenyl group, naphthyl group, A methylphenyl group, a methoxyphenyl group, etc. can be illustrated suitably. X represents a nitrogen atom. R ₃ and R ₄ each independently represent a hydrogen atom, a hydrogen atom or an aliphatic hydrocarbon group having 1 to 8 carbon atoms in which a carbon atom may be substituted with a hetero atom, and R ₃ and R ₄ are preferred. Specific examples are hydrogen atom, hydroxymethyl group, hydroxyethyl group, hydroxypropyl group, hydroxybutyl group, hydroxypentyl group, hydroxyhexyl group, hydroxyheptyl group, hydroxyoctyl group, methoxymethyl group, methoxyethyl. Group, methoxypropyl group, methoxybutyl group, methoxypentyl group, methoxyhexyl group, methoxyheptyl group, methoxyoctyl group, dihydroxymethyl group, dihydroxyethyl group, dihydroxypropyl group, dihydroxybutyl group, dihydroxypentyl group, dihydroxyhexyl group, Dihydroxy Heptyl group, dihydroxy-octyl group, aminomethyl group, aminoethyl group, aminopropyl group, aminobutyl group, aminopentyl group, an aminohexyl group, an amino heptyl group, an amino octyl be preferably exemplified, and more preferably, hydroxy Preferred examples are an ethyl group, an aminoethyl group, and a methoxyethyl group. Among the compounds represented by the general formula (5), if Specific examples of the preferred compounds, 2 - [(diphenylmethyl) amino] ethanol (Compound 5), 2 - [(methylphenyl) phenylmethyl amino] ethanol, 2- [bis (methylphenyl) methylamino] ethanol, 2 - [(ethylphenyl) phenyl-methylamino] ethanol, 2 - [(bis (ethylphenyl) methyl amino] ethanol over Le, 2 - [(methoxyphenyl) phenylmethyl amino] ethanol, 2 - [(bis (methoxyphenyl) methylamino] ethanol, 2 - [(ethoxy) phenylmethyl amino] ethanol, 2- [(bis (ethoxyphenyl) methylamino] ethanol, 2 - [(hydroxyphenyl) phenyl-methylamino] ethanol, 2 - [(bis (hydroxyphenyl) methylcarbamoyl Amino] ethanol, 2 - [(amino) phenylmethyl amino] ethanol, 2 - [(bis (aminophenyl) methylamino] ethanol, 2 - [(fluorophenyl) phenylmethyl amino] ethanol over Le, 2 - [(bis (fluorophenyl) methylamino] ethanol, 2 - [(triphenylmethyl) amino] ethanol (compound 6), 2- [diphenyl (methyl phenyl) methylamino] ethanol , 2- [bis (methylphenyl) phenyl methyl amino] ethanol, 2- [tris (methylphenyl) methylamino] ethanol, 2- [diphenyl (ethylphenyl) methylamino] ethanol, 2- [ bis (ethylphenyl) phenyl-methylamino] ethanol, 2- [tris (ethylphenyl) methylamino] ethanol, 2- [diphenyl (Metokishifu Yl) methylamino] ethanol, 2- [bis (methoxyphenyl) phenylmethyl amino] ethanol, 2- [tris (methoxyphenyl) methylamino] ethanol, 2- [diphenyl (ethoxyphenyl) methylamino ] ethanol, 2- [bis (ethoxy) phenylmethyl amino] ethanol, 2- [tris (ethoxyphenyl) methylamino] ethanol, 2- [diphenyl (hydroxyphenyl) methylamino] ethanol , 2- [bis (hydroxyphenyl) phenyl-methylamino] ethanol, 2- [tris (hydroxymethyl) methyl amino] ethanol, 2 - [(aminophenyl) diphenylmethylamino] ethanol, 2- [ bis (aminophenyl) phenyl-methylamino] ethanol, 2- [tris (aminophenyl) methylamino] et Bruno Lumpur, 2- [diphenyl (fluorophenyl) methylamino] ethanol, 2- [bis (fluorophenyl) phenyl methylamino] ethanol, 2- [tris (fluorophenyl) methylamino] ethanol and / or salts thereof pharmacologically acceptable can preferably exemplified, more preferably, 2 - [(diphenylmethyl) amino] ethanol (compound 5), 2 - [(triphenylmethyl) amino] ethanol A preferred example is diol (compound 6) and / or a pharmacologically acceptable salt thereof. When such a compound is contained in the composition together with the whitening component described later, the effect of the whitening component is enhanced and an excellent whitening action is exhibited. Further, such compounds and / or pharmacologically acceptable salts thereof have excellent safety and stability, and can be contained stably and safely in the composition.

Stated here with the compound represented by general formula (6), wherein, A is di- or triaryl the aryl is selected independently from the group consisting of ants Lumpur group having unsubstituted or substituted group represents an over Rumechiru group, X represents a nitrogen atom or an NH group, R ₅ represents a hydrogen atom or an aromatic hydrocarbon group having a carbon atom carbon atoms which may be substituted with a hetero atom 3-8, The aromatic hydrocarbon group also includes a group in which X is present in the ring. In the A, to name a specific example related to ants Lumpur group having unsubstituted or substituted group, a phenyl group, a naphthyl group, a biphenyl group, methylphenyl group, ethylphenyl group, propylphenyl group, methoxyphenyl group, ethoxyphenyl Group, propyloxyphenyl group, hydroxyphenyl group, aminophenyl group, N-methylaminophenyl group, N-ethylaminophenyl group, N-propylaminophenyl group, N, N-dimethylaminophenyl group, N, N-diethylamino Phenyl group, N, N-dipropylaminophenyl group, fluorophenyl group, difluorophenyl group, trifluoromethylphenyl group, chlorophenyl group, bromophenyl group, methylnaphthyl group, ethylnaphthyl group, propylnaphthyl group, methoxynaphthyl group, Ethoxynaphthyl group, propyloxy Synaptyl group, hydroxy naphthyl group, amino naphthyl group, N-methylamino naphthyl group, N-ethylamino naphthyl group, N-propylamino naphthyl group, N, N-dimethylamino naphthyl group, N, N-diethylamino naphthyl group, N , N-dipropylaminonaphthyl group, fluoronaphthyl group, difluoronaphthyl group, trifluoromethylnaphthyl group, chloronaphthyl group, bromonaphthyl group and the like can be suitably exemplified, more preferably phenyl group, naphthyl group, methylphenyl group A methoxyphenyl group can be preferably exemplified. X represents a nitrogen atom or an NH group. R ₅ represents a hydrogen atom or an aromatic hydrocarbon group having 3 to 8 carbon atoms in which a carbon atom may be substituted with a hetero atom, and the aromatic hydrocarbon group is a group in which X is present in the ring. Represents a group which also includes As a specific example relates to the aromatic hydrocarbon group, a phenyl group, further, the group X is present in the ring, a pyridyl group, imidazolinium group, a furyl group, a thienyl group and the like can be preferably exemplified, and more preferably, imidazolinium Le group suitably be exemplified. As a specific example relates to a compound represented by the general formula (6), 1- (diphenylmethyl) imidazole (Compound 1), 1 - [(methylphenyl) methyl] imidazole, 1- [bis ( methylphenyl) methyl] imidazole, 1 - [(ethylphenyl) methyl] imidazole, 1- [bis (ethylphenyl) methyl] imidazole, 1 - [(methoxyphenyl) methyl] imidazole, 1 - [bis (methoxyphenyl) methyl] imidazole, 1 - [(ethoxy) methyl] imidazole, 1- [bis (ethoxyphenyl) methyl] imidazole, 1 - [(hydroxyphenyl) methyl] imidazo Lumpur, 1- [bis (hydroxyphenyl) methyl] imidazole, 1 - [(amino) methyl] imidazole, 1- [bis (aminophenyl) methyl] imidazole, - [(fluorophenyl) methyl] imidazole, 1- [bis (fluorophenyl) methyl] imidazole, 1- (triphenylmethyl) imidazole (Compound 2), 1- [diphenyl (methyl phenyl) methyl ] imidazole, 1- [bis (methylphenyl) phenylmethyl] imidazole, 1- [tris (methylphenyl) methyl] imidazole, 1- [diphenyl (ethylphenyl) methyl] imidazole, 1- [bis (ethylphenyl) phenylmethyl] imidazole, 1- [tris (ethylphenyl) methyl] imidazole, 1- [diphenyl (methoxyphenyl) methyl] imidazole, 1- [bis (methoxyphenyl) phenyl methyl] imidazole, 1- [tris (methoxyphenyl) methyl] imidazole, 1- [diphenyl (ethoxy) methyl ] Imidazole, 1- [bis (methoxyphenyl) phenylmethyl] imidazole, 1- [tris (ethoxy) methyl] imidazole, 1- [diphenyl (hydroxyphenyl) methyl] imidazole, 1- [bis (hydroxyphenyl) phenylmethyl] imidazole, 1- [tris (hydroxymethyl) methyl] imidazole, 1 - [(aminophenyl) diphenylmethyl] imidazole, 1- [bis (aminophenyl) phenyl methyl] imidazole, 1- [tris (aminophenyl) methyl] imidazole, 1- [diphenyl (fluorophenyl) methyl] imidazole, 1- [bis (fluorophenyl) phenylmethyl] imidazole, 1 - [tris (fluorophenyl) methyl] imidazole and / or a pharmaceutically acceptable salt thereof pharmacologically be suitably exemplified Years, more preferably, 1- (diphenylmethyl) imidazole (Compound 1), 1- (triphenylmethyl) imidazole (Compound 2) and / or their pharmacologically acceptable salts are suitably It can be illustrated. When such a compound is contained in the composition together with the whitening component described later, the effect of the whitening component is enhanced and an excellent whitening action is exhibited. Further, such compounds and / or pharmacologically acceptable salts thereof have excellent safety and stability, and can be contained stably and safely in the composition.

  In addition, the compound represented by the general formula (1) and / or a pharmacologically acceptable salt thereof is included in the composition together with a whitening component described later, thereby preventing pigmentation due to excellent ultraviolet exposure. It exerts an effect of enhancing the preventive or ameliorating effect, particularly, the effect of preventing or ameliorating pigmentation accompanied by symptoms of incurable, dull, and rough skin caused by a decrease in cell function of keratinocytes. Such enhancement of the effect of preventing or improving pigmentation is achieved by pharmacological addition or whitening of the compound represented by the general formula (1) and / or a pharmacologically acceptable salt and a whitening component. In addition to the synergistic action, the compound represented by the general formula (1) and / or the pharmacologically acceptable salt thereof has a melanin production inhibitory action (see, for example, PCT / JP2009 / 071279), Is considered to be due to the effect of improving the delivery efficiency of the whitening component to the target site due to the effect of improving skin permeability or storage.

The compound represented by the general formula (1) and / or a pharmacologically acceptable salt thereof can be synthesized according to the method shown below or with reference, using commercially available corresponding reagents as starting materials. Furthermore, regarding a method for synthesizing a compound represented by the general formula (1) and / or a pharmacologically acceptable salt thereof not described below, the PCT filed by the present applicant is applied. / JP2009 / 071279 can be produced according to the synthesis method described in the publication . Or hunt compounds, by incorporating it in the composition with the whitening component to be described later, potentiation of preventing or ameliorating effect against pigmentation by ultraviolet rays exposure, especially, heal difficult stains caused by decreased keratinocyte cell function, dullness, It can be used to enhance the effect of preventing or improving pigmentation accompanied by rough skin symptoms, but it can be treated with a pharmacologically acceptable acid or base and converted into a salt form and used as a salt It is also possible to do. For example, mineral salts such as hydrochloride, sulfate, nitrate, phosphate, carbonate, maleate, fumarate, oxalate, citrate, lactate, tartrate, methanesulfonate, para toluenesulfonate, organic acid salts such as benzenesulfonate, sodium salt, alkali metal, calcium salts, alkaline earth metals such as magnesium salt metal, triethylamine salt and potassium salt, triethanolamine over triethanolamine salts, ammonium salts, monoethanolamine over Preferred examples include organic amine salts such as ruamine salt and piperidine salt, and basic amino acid salts such as lysine salt and arginine salt.

  The compound represented by the general formula (1) of the present invention and / or a pharmacologically acceptable salt thereof works together with a whitening component to be described later, and enhances the effect of preventing or improving pigmentation due to ultraviolet exposure or the like. In particular, pigmentation involving a decrease in keratinocyte cellular function caused by excessive accumulation and efflux of melanin, specifically, an action that enhances the prevention or improvement effect on pigmentation accompanied by irritable spots, dullness, and rough skin To achieve the above, the total amount of the composition is 0.001% to 10% by mass, more preferably 0.01% to 5% by mass, and still more preferably 0.1% to 3% by mass. % 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.

<Production Example 1: Method for producing Compound 1 and Compound 2>
Compound 1 and Compound 2 were synthesized according to the method described in JP-A-53-16879. Compound 2 can also be purchased as a reagent from Wako Pure Chemical Industries, Ltd.

１−（ジフェニルメチル）イミダゾール（化合物１）

1- (diphenylmethyl) imidazole (Compound 1)

１−（トリフェニルメチル）イミダゾール（化合物２）

1- (triphenylmethyl) imidazole (Compound 2)

<Production Example 2: Production Method of Compound 3 and Compound 4>
Ethylene glycol (3.10 g, 49.9 mmol) (Wako Pure Chemical Industries, Ltd.) and triphenyl chloromethane (1.39 g, 49.9 mmol) (Wako Pure Chemical Industries, Ltd.) in pyridine (6 mL) (OR The solution was dissolved in Kojunkaku Kogyo Co., Ltd. ), heated to 45 ° C., and stirred for 2 hours. To the reaction mixture was poured the water (50mL), and extracted with toluene (Wako Pure Chemical Industries, Ltd.). The organic layer was dried over anhydrous sulfate sodium U beam (Wako Pure Chemical Industries, Ltd.), and the solvent was evaporated under reduced pressure. The resulting crude was purified by silica gel column chromatography (chloroform (Wako Pure Chemical Industries, Ltd.): methanol (Wako Pure Chemical Industries, Ltd.) = 9: 1) to give compound 4 (yield 0.37 g, Yield 24%). Moreover, the compound 3 can be obtained by performing the same operation using diphenyl chloromethane instead of triphenyl chloromethane.

<Physical constant of compound 4>
mp. 103-106 ° C
¹ H- N MR (CDCl ₃ ): δ 3.26 (t, J = 4.5 Hz, 2H), 3.75 (t, J = 4.5 Hz, 2H), 7.23-7.54 (m, 15H).
IR (cm ⁻¹ ): 3337, 1448, 1093, 1061.

２−[（ジフェニルメチル）オキシ]エタノール（化合物３）

2 - [(diphenylmethyl) oxy] ethanol (Compound 3)

２−[（トリフェニルメチル）オキシ]エタノール（化合物４）

2 - [(triphenylmethyl) oxy] ethanol (Compound 4)

<Production Example 3: Production Method of Compound 5 and Compound 6>
Triphenylchloromethane (1.00 g, 3.58 mmol) (Wako Pure Chemical Industries) and aminoethanol (2.00 g, 32.7 mmol) were dissolved in acetonitrile (5 mL) and stirred at room temperature overnight. Water (100 mL) was poured into the reaction solution, and the precipitate was suction filtered and dried. The solid was recrystallized with ethanol (Wako Pure Chemical Industries) and water mixed solvent system to obtain compound 6 (yield 0.43 g, yield 39%). Moreover, the compound 5 can be obtained by performing the same operation using diphenylchloromethane instead of triphenylchloromethane.

<Physical constant of compound 6>
mp. 94-97 ° C
¹ H-NMR (d ₆ -DMSO): δ 2.07 (t, J = 6.0 Hz, 2H), 3.51 (t, J = 6.0 Hz, 2H), 7.15-7.42 (m , 15H).
IR (cm ⁻¹ ): 3244, 1488, 1442, 1025.

２−[（ジフェニルメチル）アミノ]エタノール（化合物５）

2 - [(diphenylmethyl) amino] ethanol (Compound 5)

２−[（トリフェニルメチル）アミノ]エタノール（化合物６）

2 - [(triphenylmethyl) amino] ethanol (Compound 6)

<Production Example 4: Production Method of Compound 7 and Compound 8>
Triphenylchloromethane (1.00 g, 3.58 mmol) dissolved in (Wako Pure Chemical Industries, Ltd.) and hydrochloric acid ethanol over triethanolamine (1.00 g, 10.3 mmol) (Wako Pure Chemical Industries, Ltd.) in pyridine (4 mL) And stirred at room temperature for 3 days. Water (200 mL) was poured into the reaction solution, and the precipitate was filtered with suction. It was suspended solids in diethyl chromatography ether, 3 (N) hydrochloric acid (Wako Pure Chemical Industries, Ltd.) was added and after stirring for 15 minutes at room temperature and suction filtered insolubles. Insoluble material was dissolved in a mixed solution of ethyl acetate (Wako Pure Chemical Industries, Ltd.) and saturated sodium hydrogen carbonate (Wako Pure Chemical Industries, Ltd.) aqueous solution, after shaking the organic layer was separated. The organic layer was dried over anhydrous sodium sulfate (Wako Pure Chemical Industries, Ltd.), suction filtered, and concentrated under reduced pressure to give the compound 8 (yield 0.31 g, 28% yield). Moreover, the compound 7 can be obtained by performing the same operation using diphenyl chloromethane instead of triphenyl chloromethane.

<Physical constant of compound 8>
mp. 87-89 ° C.
¹ H-NMR (CDCl ₃ ): δ 2.88 (t, J = 5.1 Hz, 2H), 3.14 (t, J = 5.1 Hz, 2H), 7.24-7.51 (m, 15H ).
IR (cm ⁻¹ ): 3378, 1594, 1448, 1054.

２−[（ジフェニルメチル）オキシ]エチルアミン（化合物７）

2-[(Diphenylmethyl) oxy] ethylamine (Compound 7)

２−[（トリフェニルメチル）オキシ]エチルアミン（化合物８）

2-[(Triphenylmethyl) oxy] ethylamine (Compound 8)

<Production Example 5: Method for producing Compound 9>
Chlorodiphenylmethane (0.50 g, 2.47 mmol) (Wako Pure Chemical Industries, Ltd.), pyrrolidine (0.53 g, 7.45 mmol) (TCI) and potassium iodide (0.10 g, 0.60 mmol) (Wako pure Chemical Industries, Ltd.) were added to acetonitrile (20mL) (Wako pure Chemical Industries, Ltd.), and the mixture was refluxed for 2 hours. After Ho却to room temperature, saturated sodium hydrogen carbonate (Wako Pure Chemical Industries, Ltd.) solution was added to the reaction solution, followed by extraction with ethyl acetate (Wako Pure Chemical Industries, Ltd.). The organic layer was dried over anhydrous sodium sulfate (Wako Pure Chemical Industries, Ltd.), and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent, chloroform (Wako Pure Chemical Industries, Ltd.): methanol (Wako Pure Chemical Industries, Ltd.) = 99: 1) to give compound 9 (yield 0.36 g, yield 61 %).

<Physical constant of compound 9>
mp. 69-72 ° C
¹ H-NMR (CDCl ₃ ): δ 1.73-1.79 (m, 4H), 2.40-2.44 (m, 4H), 4.15 (s, 1H), 7.12-7. 47 (m, 10H).
IR (cm ⁻¹ ): 2793, 1452, 703.

１−（ジフェニルメチル）ピロリジン（化合物９）

1- (Diphenylmethyl) pyrrolidine (Compound 9)

<Production Example 6: Method for producing Compound 10>
Pyrrolidine (0.26 g, 3.66 mmol) (Wako Pure Chemical Industries, Ltd.), triphenylchloromethane (1.02 g, 3.66 mmol) (Wako Pure Chemical Industries, Ltd.) and potassium carbonate (0.51 g, 3. 66 mmol) (Wako pure Chemical Industries, Ltd.) was added in acetonitrile (30 mL) (Wako pure Chemical Industries, Ltd.), and refluxed for 5 hours. To the reaction solution, a saturated sodium hydrogen carbonate (Wako Pure Chemical Industries, Ltd.) aqueous solution was added, and extracted with ethyl acetate (Wako Pure Chemical Industries, Ltd.). The organic layer was dried over anhydrous sodium sulfate (Wako Pure Chemical Industries, Ltd.), and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent n- hexane (Wako Pure Chemical Industries, Ltd.): ethyl acetate (Wako Pure Chemical Industries, Ltd.) = 9: 1) to give Compound 10 (Yield 0.45 g, yield 80%).

<Physical constant of compound 10>
mp. 127-129 ° C
¹ H-NMR (CDCl ₃ ): δ 1.53-1.65 (m, 4H), 2.00-2.30 (m, 4H), 7.11-7.28 (m, 5H), 7. 48-7.52 (m, 10H).
IR (cm ^-1 ): 2961, 2819, 1486, 1448, 711.

１−（トリフェニルメチル）ピロリジン（化合物１０）

1- (Triphenylmethyl) pyrrolidine (Compound 10)

<Production Example 7: Production Method of Compound 11 and Compound 12>
Piperidine (1.50 g, 17.6 mmol) (Wako Pure Chemicals), triphenylchloromethane (5.40 g, 19.4 mmol) (Wako Pure Chemicals) and potassium carbonate (2.68 g, 19.4 mmol) (Wako Pure Chemicals) ) Was added to acetonitrile (30 mL) (Wako Pure Chemical Industries, Ltd.) and refluxed for 5 hours. A saturated aqueous solution of sodium bicarbonate (Wako Pure Chemical Industries) was added to the reaction liquid, and the mixture was extracted with ethyl acetate (Wako Pure Chemical Industries). The organic layer was dried over anhydrous sodium sulfate (Wako Pure Chemical Industries), and the solvent was distilled off under reduced pressure. The obtained crude product was recrystallized using a mixed solvent of chloroform (Wako Pure Chemicals) and n-hexane (Wako Pure Chemicals) to obtain Compound 12 (yield 1.80 g, yield 31%). Moreover, the compound 11 can be obtained by performing the same operation using diphenyl chloromethane instead of triphenyl chloromethane.

<Physical constant of compound 12>
mp. 156-158 ° C
¹ H-NMR (CDCl ₃ ): δ 0.70-3.50 (m, 10H), 7.14-7.80 (m, 15H).
IR (cm < ^-1 >): 2923, 1485, 1448, 708.

１−（ジフェニルメチル）ピペリジン（化合物１１）

1- (Diphenylmethyl) piperidine (Compound 11)

１−（トリフェニルメチル）ピペリジン（化合物１２）

1- (Triphenylmethyl) piperidine (Compound 12)

<Whitening component of the present invention>
The composition of the present invention comprises 1) a compound represented by the general formula (1) and / or a pharmacologically acceptable salt thereof, and 2) a whitening component. The whitening component of the present invention can be applied without particular limitation as long as it has a whitening action. Specific examples include a melanin production inhibitor, an α-MSH inhibitor, a melanocyte dendrite elongation inhibitor, Proton pump inhibitors and the like can be suitably exemplified. The whitening component of the present invention not only has a whitening effect itself, but also is contained in the composition together with the compound represented by the general formula (1) and / or a pharmacologically acceptable salt thereof. In addition, the effect of enhancing the preventive or ameliorating effect on pigmentation by exposure to ultraviolet rays, and in particular, the enhancing effect on the preventing or improving effect on pigmentation accompanied by irritable blemishes, dullness, and rough skin caused by keratinocyte cell function decrease. In those people who have worsened skin symptoms due to pigmentation, which is associated with decreased cell function of keratinocytes, when the stratum corneum is prepared, the appearance rate of nucleated cells is higher than the average, and the skin Skin symptoms such as delamination of the skin are observed. The composition of the present invention is particularly preferably used for a person exhibiting the above-mentioned skin symptoms. It is preferable to set a subject to be administered using symptoms as an index. Moreover, as said whitening component, forms, such as a simple chemical substance or the plant-derived extract containing the said compound, can be illustrated suitably. 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 such a whitening component is contained in the composition together with the compound represented by the general formula (1) and / or a pharmacologically acceptable salt thereof, a whitening component selected from the group consisting of the whitening component is used. Only one kind can be contained, or two or more kinds can be contained in combination.

Of whitening component of the present invention, it describes a melanin production inhibitor. 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. Among such melanin production inhibitors, if specifically exemplified preferred, 4-alkyl-les sols Sino Lumpur and / or their pharmacologically acceptable salts, ascorbic acid derivatives and / or their pharmacologically 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 pharmacologically acceptable salts, pantethein-S-sulfonic acid and / or pharmacologically acceptable salts thereof . In addition to the melanin production inhibitor, 4-alkoxysalicylic acid such as 4-methoxysalicylic acid and / or pharmacologically acceptable salts thereof, 5,5′-dipropyl-biphenyl-2,2′-dio over biphenyl derivative and / or a pharmaceutically acceptable salt thereof pharmacologically include Le, not such as nicotinic acid amide derivatives and / or their pharmacologically acceptable salts, Reno Lumpur acids such as nicotinic acid amide Saturated fatty acids and / or pharmacologically acceptable salts thereof can also be suitably exemplified.

It describes the 4-alkyl-les sols Sino Lumpur and / or a pharmaceutically acceptable salt thereof pharmacologically. 4-alkyl-les sols Sino Lumpur derivatives of the present invention may, if melanin production inhibitory effect of a 4-alkyl-les sols Sino Lumpur and / or their pharmacologically acceptable salts, no particular limitation without adaptation it is possible to, more preferably, the carbon number of 4-position alkyl group of 4-alkyl-les sols Sino Lumpur is a linear or branched alkyl group having 1 to 10 carbon atoms, more preferably a carbon number 3-7 linear or a branched alkyl group of 4-alkyl-les sols Sino Lumpur and / or their pharmacologically acceptable salts are suitably be exemplified. If Specific examples of the preferable relates to the aforementioned 4-alkyl-les sols Sino Lumpur and / or a pharmaceutically acceptable salt thereof pharmacologically, 4 Mechirurezorushino Lumpur, 4 Echirurezorushino Lumpur, 4- n- propyl les sols Sino Lumpur, 4- (1-methylethyl) resorcinol Lumpur, 4-n-Buchirurezorushino Lumpur,
4- (2-methylpropyl) resorcinol Lumpur, 4- (1-ethylpropyl) resorcinol Lumpur, 4- (1-ethyl-2-methylpropyl) resorcinol Lumpur, 4- (1-isopropyl-2-methyl propyl) resorcinol Lumpur, 1 - isopropyl-2-methylpropyl les sols Sino Lumpur, 4 - (1-methylpropyl) resorcinol Lumpur, 4- (1-methylbutyl) resorcinol Lumpur, 4-tert Buchirurezorushino Lumpur and / or their pharmacologically acceptable salts, and can be preferably exemplified, and more preferably, 4-n-Buchirurezorushino Lumpur and / or a pharmacologically acceptable salt thereof suitably be exemplified.

The 4-alkyl-les sols Sino Lumpur and / or their pharmacologically acceptable salts, the compounds represented by the general formula (1), its isomers and / or their pharmacologically acceptable It works together with the added salt to prevent or improve pigmentation caused by exposure to ultraviolet rays, etc., and in particular, it has the effect of preventing or improving pigmentation accompanied by symptoms of incurable, dull, and rough skin caused by decreased cellular function of keratinocytes. Therefore, the total amount is 0.0001% to 5% by mass, more preferably 0.001% to 3% by mass, and still more preferably 0.01% to 2% by mass with respect to the total amount of the composition. It is preferable to do. 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-alkyl-les sols Shino Lumpur, the presence of zinc chloride carboxylic acid and resorcinol with the corresponding alkyl group, fused, a method of reducing the zinc amalgam / hydrochloric acid, or alcohol with the corresponding alkyl group known synthetic methods such as the condensation of Lumpur and resorcinol at high temperature of 200 to 400 ° C. (e.g., 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.

The ascorbic acid, it describes its derivatives and / or their pharmacologically acceptable salts. The ascorbic acid , derivative thereof and pharmacologically acceptable salt thereof of the present invention are special if it is ascorbic acid having a melanin production inhibitory effect, derivative thereof and / or pharmacologically acceptable salt thereof. It can be applied without limitation, and more preferably, water-soluble ascorbic acid derivatives and / or pharmacologically acceptable salts thereof can be preferably exemplified. Relates acceptable salts wherein the ascorbic acid derivative and / or their pharmacologically, to name preferred ones specifically, ascorbic acid, ascorbic acid phosphate ester, ascorbic acid-2-grayed Le Koshido (simply, ascorbic And / or pharmacologically acceptable salts thereof, and more preferably, ascorbic acid, ascorbic acid-2-glucoside and / or their pharmacologically acceptable salts. An acceptable salt can be preferably exemplified. Such ascorbic acid, ascorbic acid-2-glucoside and / or their pharmacologically acceptable salts are excellent in melanin production inhibitory action and have high water solubility, and thus are highly versatile in formulation.

  The ascorbic acid, derivative thereof and / or pharmacologically acceptable salt thereof works together with the compound represented by the general formula (1) and / or pharmacologically acceptable salt thereof, and ultraviolet rays. In order to exert an effect of enhancing the prevention or improvement effect against pigmentation accompanied by symptoms of incurable, dullness, and rough skin caused by the decrease in cell function of keratinocytes, especially the enhancement effect of prevention or improvement effect on pigmentation by exposure It is preferable to contain 0.01% by mass to 10% by mass, and more preferably 0.05% by mass to 5% by mass with respect to the total amount of the object. 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.

It describes the hydroquinone derivative and / or a pharmaceutically acceptable salt thereof pharmacologically said. The hydroquinone derivatives of the present invention and their pharmacologically acceptable salts are applicable without particular limitation as long as they are hydroquinone derivatives having a melanin production inhibitory action and / or their pharmacologically acceptable salt conductors. If a preferable thing is specifically illustrated, a hydroquinone glycoside can be illustrated suitably. The carbohydrate portion of the hydroquinone glycosides, L- arabinose, D- xylose, D- ribose, D- Kishiruro over scan, D- lyxo over scan, D- Libro fifth over scan, etc. carbon sugar, D- glucose, D- galactose, D- mannose, D- Tagaro over scan, D- fructose, hexose such as L- Sorbo over the scan, D- glucosamine, D- Amino acid sugars such as 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, and L-iduronic acid or their methyl compounds and acetyl compounds can be preferably exemplified. . Wherein among the hydroquinone derivatives, and more preferred are salts arbutin and / or a pharmacologically acceptable has the chemical structure hydroquinone and glucose is bonded suitably be exemplified.

The hydroquinone derivative can be obtained by a conventional method from hydroquinone and a corresponding sugar. For example, arbutin, a solution consisting of hydroquinone and glucose, beta-glucosidase peptidase enzymatic reaction by can be synthesized using (e.g., JP-A-05-176785).

  Further, the hydroquinone derivative and / or pharmacologically acceptable salt thereof works together with the compound represented by the general formula (1) and / or pharmacologically acceptable salt thereof, and is exposed to ultraviolet rays. In order to exert an effect of enhancing the prevention or improvement effect on pigmentation accompanied by symptom of incurable, dull, and rough skin caused by reduced keratinocyte cell function The total amount is preferably 0.001% to 5% by mass, more preferably 0.1% 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.

The tranexamic acid, it describes its derivatives and / or their pharmacologically acceptable salts. The tranexamic acid of the present invention, a derivative thereof and / or a pharmacologically acceptable salt thereof is tranexamic acid having a melanin production inhibitory effect, a derivative thereof and / or a pharmacologically acceptable salt thereof. It can be applied without any particular limitation. Specific examples of the tranexamic acid derivatives and pharmacologically acceptable salts thereof include tranexamic acid, tranexamic acid methylamide and / or pharmacologically acceptable salts thereof. More preferably, tranexamic acid and / or a pharmacologically acceptable salt thereof can be preferably exemplified.

The tranexamic acid , derivative thereof and / or pharmacologically acceptable salt thereof works together with the compound represented by the general formula (1) and / or pharmacologically acceptable salt thereof. To enhance the prevention or improvement of pigmentation caused by UV exposure, especially for the prevention or improvement of pigmentation accompanied by incurable, dull, and rough skin symptoms caused by decreased cell function of keratinocytes The total amount of the composition is 0.01% by mass to 10% by mass, more preferably 0.05% by mass to 5% by mass, and more preferably 0.1% by mass to 3% by mass. 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.

The vitamin E, it describes its derivatives and / or their pharmacologically acceptable salts. 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. The the vitamin E, if specifically mentioned as preferred relates derivatives and pharmaceutically acceptable salts thereof pharmacologically, vitamin E, vitamin E Asete over preparative, vitamin E Nikochine over preparative, vitamin E Orote over DOO and / Alternatively, pharmacologically acceptable salts thereof can be preferably exemplified, and more preferably, vitamin E and / or pharmacologically acceptable salts thereof can be suitably exemplified.

  Further, the vitamin E, derivative thereof and / or pharmacologically acceptable salt thereof works together with the compound represented by the general formula (1) and / or pharmacologically acceptable salt thereof. In order to exert an effect of preventing or improving pigmentation caused by ultraviolet ray exposure, especially for preventing or improving pigmentation accompanied by symptoms of intractable blemishes, dullness, and rough skin caused by decreased cellular function of keratinocytes. It is preferable to contain 0.05 mass%-10 mass% with respect to the whole quantity, More preferably, 0.2 mass%-5 mass%, More preferably, it contains 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.

It describes the of pantetheine -S- sulfonic acid and / or a pharmacologically acceptable salt thereof. 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, sodium salts, alkali metal salts such as potassium salts, calcium salts, alkaline earth metal salts such as magnesium salt, ammonium salt, triethylamine salt, triethanolamine over triethanolamine salts, organic amine salts such as monoethanolamine over triethanolamine salts, lysine salts, Preferred examples include basic amino acid salts such as arginine salts. 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 an external preparation for skin. 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, pantethine-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, “pantethine 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 pharmacologically acceptable salt thereof together with the compound represented by the general formula (1) and / or pharmacologically acceptable salt thereof In order to exert an enhancement effect on the prevention or improvement effect on pigmentation accompanied by symptoms of irritable skin, dullness, and rough skin caused by reduced cell function of keratinocytes Is 0.001% by mass to 1.0% by mass, more preferably 0.005% by mass to 0.8% by mass, and more preferably 0.01% by mass to 0.00% by mass relative to the total amount of the composition. 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.

It explains to the α-MSH production inhibitor of the. 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. As the component having an α-MSH production inhibitory action of the present invention, for example, it has 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. A component can be illustrated suitably. As the component having an α-MSH production inhibitory action, a plant extract obtained from a plant belonging to the leguminous family Clara can be preferably exemplified, and more preferably, a plant extract obtained from the leguminous family Clara is suitably used. It can be illustrated. 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) and / or a pharmacologically acceptable salt thereof, and enhances the effect of preventing or improving pigmentation due to UV exposure. In order to exert an effect of preventing or improving pigmentation accompanied by symptoms of incurable skin, dullness, and rough skin caused by keratinocyte cell function decrease, the total amount of the composition is 0.00001% by mass. ˜15% by mass, more preferably 0.0001% by mass to 10% by mass, and more preferably 0.01% 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.

It describes the dendrite elongation inhibitor of the melanocytes. 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 pigmentation due to increased melanin production, the melanocyte dendrite elongation inhibitor is also effective for pigmentation caused by increased movement 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) and / or a pharmacologically acceptable salt thereof, and enhances the effect of preventing or improving pigmentation by exposure to ultraviolet rays. In order to exert an effect of preventing or improving the pigmentation accompanied by symptoms of incurable skin, dullness, and rough skin caused by a decrease in cell function of keratinocytes, the total amount of the composition is 0.01% by mass. -10% by mass, 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.

It describes the proton pump inhibitor. 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 effect in a cell or organelle provides ion channel that acts pH-dependent, enzymes (e.g., tyrosinase over Ze, etc.) a major effect on the biological activity or function of a biological functional molecules such as. Tyrosinase over enzyme is a key enzyme in melanin production, since significantly affected by pH variations, melanin reduces the tyrosinase over peptidase activity by acidification is suppressed. 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 Hetchima, a plant belonging to the genus Hydrangeaceae, a plant belonging to the genus Sarcophagus matsuhodo, a plant belonging to the genus Leguminosae can be suitably exemplified, more preferably from the genus Thymus resulting plant extraction, plant extracts obtained from leguminous Clara genus Clara, a plant extract obtained from the ginger family ginger genus ginger, a plant extract obtained from Araceae iris genus calamus, obtained from Cucurbitaceae gourd genus loofah Plant extract, plant extract obtained from Hydrangea hydrangea amacha, Sarnokoshi Ke family Wolfiporia Extensa sclerotia plant extract obtained from Bukuryou, plant extract obtained from leguminous clover genus Kihagi, plant extract obtained from leguminous gores genus Toukusahagi be suitably be exemplified.

  In order for the component having the proton pump inhibitory action to work together with the compound represented by the general formula (1) and / or a pharmacologically acceptable salt thereof, On the other hand, the total amount is preferably 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 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.

Of the whitening components such as melanin production inhibitor, α-MSH inhibitor, melanocyte dendrite elongation inhibitor, proton pump inhibitor, etc., which are essential components of the present invention, the compound may be used as it is. It can be used as a pharmacologically acceptable salt form. These salts can be used without particular limitation as long as they are used in foods, cosmetics (external preparations for skin), pharmaceuticals, and the like. For example, alkali salts such as sodium salts and potassium salts can be used. metal salts, calcium salts, alkaline earth metal salts such as magnesium salt, ammonium salt, triethylamine salt, triethanolamine over triethanolamine salts, organic amine salts such as monoethanolamine over triethanolamine salts, lysine salts, basic amino acid salts such as arginine salt It can illustrate suitably. 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 contained in the composition together with the compound represented by the general formula (1) and / or a pharmacologically acceptable salt thereof, thereby preventing or improving pigmentation due to excellent UV exposure. It exhibits the effect of enhancing or preventing or improving the pigmentation accompanied by symptoms of incurable, dull, and rough skin, which are related to the decrease in cellular function of keratinocytes due to the enhanced effect of action, in particular, excessive transport of melanin, accumulation and delayed discharge. Such an effect of enhancing the prevention or improvement of pigmentation is in addition to the prevention or improvement of pigmentation possessed by the whitening component as well as the compound represented by the general formula (1) and / or pharmacologically acceptable. This is considered to be due to the pharmacological addition or synergistic action between the salt to be used and the whitening component, and further the effect of improving the delivery efficiency of the whitening component to the target site.

<Composition of the present invention>
The composition of the present invention comprises 1) a compound represented by the general formula (1) and / or a pharmacologically acceptable salt thereof, and 2) a whitening component. The compound represented by the general formula (1) of the present invention, its isomer and / or pharmacologically acceptable salt thereof is contained in the composition together with the above-described whitening component, whereby a dye by exposure to ultraviolet rays. Enhancement of prevention or improvement of deposition prevention, especially, enhancement of prevention or improvement of pigmentation associated with irritable stagnation, dullness, and rough skin due to decreased cellular function of keratinocytes due to excessive transport, accumulation and elimination of melanin Demonstrate the effect. Such an enhancement effect of the prevention or improvement of pigmentation has a pharmacological effect in the whitening action of the compound represented by the general formula (1) and / or a pharmacologically acceptable salt and a whitening component. In addition to the additive or synergistic action, the effect of improving the delivery efficiency of the whitening component to the target site, skin retention or permeability, and the compound represented by the general formula (1) and / or their pharmacology This is considered to be due to the pharmacological activity possessed by the chemically acceptable salt or whitening component. Also, in human pigmentation occurs by the ultraviolet exposure, at the same time, overproduction of melanin in melanocytes, as well as, cellular inactivation of keratinocytes due to excessive transfer of melanin to the keratinocytes, te oleate over bar delay deterioration of skin symptoms due to bad over di is often it is observed that has arisen and the like. The composition of the present invention is used for a person who exhibits intractable blemishes, dullness, and rough skin caused by phenomena such as excessive transport, accumulation and discharge delay of melanin in addition to preventing or improving pigmentation. Is preferred. 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 preparation of a composition comprising 1) a compound represented by the general formula (1) and / or a pharmacologically acceptable salt thereof, and 2) a whitening component, It can contain optional ingredients used in the formulation of normal foods, pharmaceuticals, cosmetics and the like. Examples of such optional ingredients, if oral dosage composition, for example, excipients such as lactose, white sugar, starch, cellulose chromatography scan, acacia, binders such as hydroxypropylcellulose over scan, carboxymethylcellulose over scan sodium, disintegrating agents such as carboxymethylcellulose over scan calcium, soy lecithin, surfactants such as sucrose fatty acid esters, sweetening agents such as multitrack Lumpur and sorbitol Lumpur, acidulant such as citric acid, phosphates such as 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 cosmetics, as long as it can apply an oil-in-water emulsifier type, no particular limitation, for example, essences, milks, basic cosmetics such as creams, under-over menu over up, van Activation, Ji chromatography Kukara over, mascara, make-up cosmetics such as eyeliner over, such as hair cosmetics such as Heakuri over-time can be suitably 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. Examples of such optional components, e.g., macadamia nut oil, Abou transient oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower over <br/> oil, cottonseed oil, jojoba oil, coconut oil, palm oil, liquid lanolin, hydrogenated coconut oil, hydrogenated oil, Japan wax, hydrogenated castor oil, beeswax, candelilla wax, carnauba wax, insect wax, lanolin, reduced lanolin, hard lanolin, oils such jojoba wax, waxes; liquid paraffin, Hydrocarbons such as squalane, pristane, ozokerite, 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; Sechiruaruko Lumpur, stearyl alcohol, Isosute Riruaruko Lumpur, behenyl alcohol, octyl dodecanoate Lumpur, myristyl alcohol, higher alcohols such as cetostearyl alcohol; isooctane cetyl, isopropyl myristate, isostearate hexyl decyl, diisopropyl adipate, sebacic acid di-2-ethylhexyl, cetyl lactate, diisostearyl malate, di-2-ethyl hexanoate of ethylene glycol, neopentyl glycol dicaprate, glyceryl di-2-heptylundecanoate, tri-2-ethylhexanoate glycerin , tri-2-ethylhexanoate trimethylol over trimethylolpropane triisostearate trimethylol over trimethylolpropane, synthetic ester oils such as tetra-2-ethylhexanoate pentane pentaerythritol; dimethyl polysiloxane, methylphenyl Polysiloxane, linear polysiloxanes such as diphenyl polysiloxane; octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, cyclic polysiloxanes such as dodeca methylcyclohexane siloxane; amino-modified polysiloxane, polyether chromatography ether-modified polysiloxane, alkyl-modified poly siloxanes, oils such silicone over emissions oils of modified polysiloxanes and fluorine-modified polysiloxane; fatty acid soap (sodium laurate, sodium palmitate), potassium lauryl sulfate, an anionic surface such as alkyl sulfate triethanol over Ruamin'e over ether Activating agents; cationic surfactants such as stearyltrimethylammonium chloride, benzalkonium chloride, laurylamine oxide; imidazoline-based amphoteric surfactants (2-cocoyl-2-yl) Amphoteric surfactants such as midazolinium hydroxide-1-carboxyethyloxy disodium salt), betaine surfactants (alkyl betaine, amide betaine, sulfobetaine, etc.), acylmethyl taurine; sorbitan fatty acid esters ( sorbitan monostearate over preparative, sorbitan sesquioleate etc.), glycerol fatty acids (glycerol monostearate, etc.), propylene glycol fatty acid esters (monostearate propylene glycol, etc.), hardened castor oil derivatives, glycerin alkyl error over ether, POE sorbitan fatty acid esters (POE sorbitan monooleate over preparative, polio monostearate key sorbitan, etc.), POE sorbitol fatty acid esters (POE- sorbit monolaurate over preparative etc.), POE glycerin fatty Esters (POE- glyceryl monoisostearyl array over preparative etc.), POE fatty acid esters (polyethylene glycol Rumonoore over preparative, POE Jisuteare over preparative etc.), POE alkyl ether over ethers (POE2- octyldodecyl error over ether, etc.), POE alkylphenyl et chromatography ethers (POE nonylphenyl error over ether, etc.), Pluronic type compound, POE-POP alkyl ether over ethers (POE-POP2- decyltetradecyl et chromatography ether, etc.), Tetronic compounds, 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 clouds , Calcium carbonate, magnesium carbonate, silicic anhydride (silica), aluminum oxide powder such as barium sulfate; surface may be treated with, red iron oxide, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, iron blue, titanium oxide, inorganic pigments zinc oxide; may be surface treated mica titanium, Sakanarinhaku, Pas Lumpur agent such as bismuth oxychloride; which may be les over key of red 202 No., Red 228, Red 226, Yellow No. 4, Blue No. 404, Yellow No. 5, Red No. 505, Red No. 230, Red No. 223, Orange No. 201, Red No. 213, Yellow No. 204, Yellow No. 203, blue No. 1, green No. 201, purple No. 201, organic dyes red No. 204, etc., polyethylene powder, polymethyl methacrylate, nylon powder, organic powders such organopolysiloxane elastomers Paraaminobenzoic acid UV absorbers; Anthranilic acid UV absorbers; Salicylic acid UV absorbers; Cinnamic acid UV absorbers; Benzophenone UV absorbers; Sugar UV absorbers; 2- (2′-hydroxy- 5'-t-octylphenyl) benzotriazole, 4-methoxy-4'-t-butyl-dibenzo yl ultraviolet absorbers such as methane; ethanol, lower alcohols such as isopropanol Lumpur; vitamin a or a derivative thereof , vitamin B ₆ hydrochloride, vitamin B ₆ Toriparumite over preparative, vitamin B ₆ Jiokutanoe over preparative, vitamin B ₂ or derivatives thereof, vitamin B _12, vitamin B such as vitamin B ₁₅ or a derivative thereof; alpha-tocopherol Lumpur, β- tocopherol Lumpur, .gamma. tocopherol Lumpur, vitamin E such as vitamin E Asete over preparative, vitamin D, vitamin H, punt Ten acid, pantethine, vitamins such as pyrroloquinoline quinone and the like; antibacterial agents such as phenoxyethanol Lumpur; hectorite, and organic-modified clay minerals such as dimethyl distearyl ammonium modified hectorite may be preferably exemplified.

The skin external preparation of the present invention contains the essential components described above, and preferably takes the form of an emulsifier. The form of the emulsifier form may be either the water-in-oil emulsifier form or the oil-in-water emulsifier form, but the oil-in-water emulsifier form is particularly preferred. Here, the water-in-oil emulsifier type is a word called comprehensively the emulsifier shape with the oil phase to the Foreign Minister, may also contain an aqueous phase to the internal phase, have the emulsion, such as oil-in-water emulsions You may do it. Similarly, the oil-in-water emulsifier form is a general term for an emulsion having an aqueous phase in the outer phase, and may have an oil phase in the inner phase or an emulsion such as a water-in-oil emulsion. Good .

The skin external preparation of the present invention can contain a non-surfactant used in skin external preparations such as ordinary cosmetics. Furthermore, it is also preferable to contain an alkyl-modified carboxyvinyl polymer and / or a salt thereof in the sense of keeping the emulsified state stable. The preferred content of such components, relative to the total amount of the skin treatment composition is from 0.01 wt% to 0.5 wt%, more preferably from 0.05 wt% to 0.3 wt%. Such a component is preferably contained also in that sense because it forms a composite film with the essential ingredient amodimethicone after administration to the skin and enhances the effect of amodimethicone. Such alkyl-modified carboxyvinyl polymers include commercially available products, which can be purchased and used. Preferable commercial products are “Pemuren (registered trademark) TR-1” and “Pemuren (registered trademark)” which are commercially available from Nippon Surfactant Co., Ltd. and are alkyl-modified with an alkyl group having 10 to 30 carbon atoms. TR-2 "," Carbopol (registered trademark) 1382 "commercially available from BF Goodrich (USA), etc., and carboxyvinyl polymers that are not alkyl-modified include BF Goodrich (USA) “Carbopol (registered trademark) Ultrez 10”, “Carbopol (registered trademark) 940”, and the like. Such hydrophilic polymers may be used alone or in combination of two or more. The oil-in-water emulsion composition of the present invention preferably contains 0.05 % by mass to 1% by mass of such a hydrophilic polymer, and preferably contains 0.08 % by mass to 0.5% by mass. More preferred. When less than this, an emulsification system will become unstable, and when more than this, the viscosity of a system will become high too much and applicability | paintability will worsen. In addition, when such an alkyl-modified carboxyvinyl polymer and / or a salt thereof is contained, it is preferable to contain a glyceryl alkyl ether or a glyceryl alkenyl ether in order to reinforce the emulsion structure produced by the polymer. The glyceryl alkyl ethers, Bachiruaruko Lumpur, as the glyceryl alkenyl ether, selachyl alcohol suitably be exemplified. Such ethers are preferably contained in an amount of 0.1% by mass to 1% by mass, and the content is preferably equivalent to or 5 times the content of the alkyl-modified carboxyvinyl polymer. This is because this amount range is suitable for strengthening the emulsifier form.

Further, among the above optional components, nonionic surfactants are particularly preferable, and among them, lipophilic surfactants that are excellent in structure formation in an emulsified state are preferable. As the ionic surfactant, sorbitan stearate, glycerin monostearate and the like can be particularly preferably exemplified. The preferable content of such a component is 0.1 % by mass to 5% by mass, and more preferably 0.2 % by mass to 3% by mass. By adding such a component, the adhesiveness with the skin becomes excellent.

  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 8: Production 1 of composition of the present invention (skin external preparation)>
According to the formulations shown in Tables 1 and 2, the composition of the present invention (external preparation for skin) was prepared. That is, b, heating the components b) and (c to 80 ° C., was slowly added neutralized with stirring Ha to B, Lee gradually while stirring was added, homogenized emulsified particles by homomixer over emulsions ( Cosmetics 1-14) were obtained. 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 prescription components of the cosmetic 5 and “whitening component of the present invention” was replaced with “water”. Comparative Example 2 in which “the compound represented by the general formula (1) of the present invention” and “Whitening component of the present invention” were both replaced with “water” were produced.

<Test Example 1: Evaluation 1 of pigmentation inhibitory action of the composition of the present invention (external preparation for skin)>
Using the oil-in-water emulsifier type cosmetics (cosmetics 1 to 14) and the cosmetics of Comparative Examples 1 to 3, the pigmentation inhibitory effect was examined. The panelists over the back who participated voluntarily, providing a test site of 1.5cm × 1.5cm to test the first day (day 1), skin brightness (L * value) of the color difference meter of the test site (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 to 14 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 1-14 which are the skin external preparations of this invention have the outstanding pigmentation inhibitory effect. Although even pigmentation inhibition Comparative Example 1 and Comparative Example 2 was observed, the effect was weaker as compared with the cosmetic 1-14.

<Production Example 9: Production 2 of composition of the present invention (skin external preparation)>
Cosmetics in which the contents of the “compound represented by the general formula (1) of the present invention (compound 12)” and “whitening component of the present invention” contained in the cosmetic 5 are changed (cosmetics 15 to 24) was prepared according to the production method described in Example 1, and the pigmentation inhibitory action by UV exposure was examined. The contents of the components are as shown in Table 4. Moreover, the change of the mass% by the increase / decrease in the said component was adjusted by changing the mass% of water.

<Test Example 2: Evaluation 2 for inhibiting pigmentation of composition of the present invention (external preparation for skin)>
The oil-in-water emulsifier type cosmetics 15 to 24 produced by the method described in Example 3 and further Comparative Example 3 produced according to the method described in Example 1 were applied according to the test method described in Example 2. The pigmentation inhibitory effect of Samples 15 to 24 and Comparative Example 3 was evaluated. The results are shown in Table 5.

<Manufacture example 10: Composition 3 of this invention (skin external preparation) manufacture>
An attempt was made to prepare cosmetic 25 in which “Pemlen TR-2” was replaced with POE (25) stearic acid in the formulation components of cosmetic 5 described in Example 1, and the cosmetic 25 was separated immediately after production. Thus, an emulsion was not obtained.

< Test Example 3> Evaluation of inhibitory effect on pigmentation of composition (external preparation for skin) of the present invention 3>
The cosmetics 2, cosmetics 5-9, and comparative examples 1-3 manufactured according to the method described in Example 1 were evaluated for pigmentation inhibitory action according to the following procedure. When selecting panelists with more than the average melanin, the sample of stratum corneum cells collected from the skin by adhesive tape stripping was visualized by melanin staining using an aqueous silver nitrate solution, and this was determined by observing under a microscope. did. In the determination, the determination was made by scoring around the average existence situation. Furthermore, among the panelists, a person who has a nucleated cell appearance rate higher than the average or has a higher degree of delamination than the average using a stratum corneum sample was selected by observation and used as a paneler. Panels who participated voluntarily with the above characteristics were divided into 1.5 cm x 1.5 cm parts on the upper and lower dorsum of the upper arms, and a measurement part was provided. Ultraviolet irradiation with a minimum amount of erythema (1 MED) was performed once a day. Irradiated 3 times for 3 consecutive days. From 1 day after the end 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 the 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 2 and the cosmetics 5-9 which are the skin external preparations of this invention show the outstanding pigmentation inhibitory effect.

<Production Example 12: Production 1 of Composition (Health Food) of the Present Invention>
According to the prescription shown in Table 7 and Table 8, health foods (health foods 1 to 8) were prepared. That is, the formulation components rolling phase granulated with 10 parts by weight of water (manufactured by Fuji Paudal Co., Ltd., "New over Marumerizer over"), to give a tablet form of the health food and then pressed into tablets. In addition, the unit of the numerical value in a table | surface represents a weight part. This health food was found to have an excellent pigmentation prevention or improvement effect.

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

Claims (20)

1) A compound represented by any one of the following general formulas (3) to (6) and / or a pharmacologically acceptable salt thereof, 2) a whitening component, and the content of the whitening component is A skin external preparation , characterized by being 0.000001% by mass to 15% by mass based on the total amount of the external preparation for skin.

[In Formula (3), A represents a diphenylmethyl group or a triphenylmethyl group,
X represents a ChissoHara child,
R ₁ has 3 carbon atoms in which a hydrogen atom or a carbon atom may be substituted with a nitrogen atom or an oxygen atom.
Represents 8 cyclic aliphatic hydrocarbon group, the ring of the cyclic aliphatic hydrocarbon group, the other terminal of R ₁ is Ru is formed by combining again to X. ]

[In Formula (4), A represents a diphenylmethyl group or a triphenylmethyl group,
X represents an oxygen atom,
R ₂ has 1 carbon atom in which a hydrogen atom or a carbon atom may be substituted with a nitrogen atom or an oxygen atom.
Represents an aliphatic hydrocarbon group of ~ 4. ]

[In Formula (5), A represents a diphenylmethyl group or a triphenylmethyl group,
X represents a nitrogen atom,
R ₃ and R ₄ each independently represent a hydrogen atom or a C 1-8 aliphatic hydrocarbon group in which a hydrogen atom or a carbon atom may be substituted with a nitrogen atom or an oxygen atom. ]

[In Formula (6), A represents a diphenylmethyl group or a triphenylmethyl group,
X represents a ChissoHara child,
R ₅ has ₃ carbon atoms in which a hydrogen atom or a carbon atom may be substituted with a nitrogen atom or an oxygen atom.
Represents 8 aromatic hydrocarbon group, the ring of the aromatic hydrocarbon group above, other end of R ₅ is Ru is formed by combining again to X. ] In the compound represented by the general formula (3), R ₁ is a pyrrolidino group, piperidino group, piperazino group, or morpholino group, and the other end of R ₁ is bonded again to X to form a ring. The skin external preparation of Claim 1 containing the 1 type (s) or 2 or more types chosen from a compound. In the compound represented by the general formula (4), R ₂ is a hydroxyethyl group, an aminoethyl group,
Or the skin external preparation of Claim 1 containing the 1 type (s) or 2 or more types chosen from the compound which is a methoxyethyl group. The compound represented by the general formula (5) is one or two selected from compounds in which R ₃ and R ₄ are each independently a hydrogen atom, a hydroxyethyl group, an aminoethyl group, or a methoxyethyl group. The skin external preparation of Claim 1 containing the above. Compound represented by the general formula (6), an R ₅ Gapi lysyl group, or an imidazolyl group, selected from compounds other end of R ₅ are bonded again to X to form a ring 1 The skin external preparation of Claim 1 containing a seed | species or 2 or more types.   The compound represented by the general formula (3) is 1- (diphenylmethyl) pyrrolidine (compound 9), 1- (triphenylmethyl) pyrrolidine (compound 10), 1- (diphenylmethyl) piperidine (compound 11), The skin external preparation of Claim 2 containing the 1 type (s) or 2 or more types chosen from 1- (triphenylmethyl) piperidine (compound 12). The compound represented by the general formula (4) is 2-[(diphenylmethyl) oxy] ethanol (compound 3), 2-[(triphenylmethyl) oxy] ethanol (compound 4), 2-[(
The skin according to claim 3, comprising one or more selected from the group consisting of diphenylmethyl) oxy] ethylamine (compound 7) and 2-[(triphenylmethyl) oxy] ethylamine (compound 8). Topical agent.   The compound represented by the general formula (5) is selected from the group consisting of 2-[(diphenylmethyl) amino] ethanol (compound 5) and 2-[(triphenylmethyl) amino] ethanol (compound 6). The skin external preparation of Claim 4 containing 1 type or 2 types.   The compound represented by the general formula (6) is one or two selected from the group consisting of 1- (diphenylmethyl) imidazole (compound 1) and 1- (triphenylmethyl) imidazole (compound 2). The skin external preparation of Claim 5 containing this.   0.001% by mass to 10% by mass of the compound represented by any one of the general formulas (3) to (6) and / or a pharmacologically acceptable salt thereof with respect to the total amount of the external preparation for skin The skin external preparation as described in any one of Claims 1-9 characterized by the above-mentioned. 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 as described in any one of Claims 1-10.   The melanin production inhibitor includes 4-alkylresorcinol and salts thereof, ascorbic acid derivatives and salts thereof, hydroquinone derivatives and salts thereof, tranexamic acid derivatives and salts thereof, vitamin E derivatives and salts thereof, and pantethein-S-sulfonic acid and The skin external preparation of Claim 11 containing at least 1 sort (s) selected from the salt.   The said external preparation for skin of Claim 11 containing the plant extract obtained from the leguminous Clara genus Clara, the said alpha-MSH inhibitor.   The melanocyte dendrite elongation inhibitor includes at least one selected from methylophiopogononone B, sophoraflavanone A, a plant extract obtained from Asteraceae and a plant extract obtained from Asteraceae. The skin external preparation of Claim 11.   The proton pump inhibitor is a plant extract obtained from Lamiaceae genus Thymus, plant extract obtained from Leguminosae Clara, plant extract obtained from Ginger ginger ginger, Cytoaceae ginger From a plant extract obtained from the cucurbitaceae genus Hachima, a plant extract obtained from the genus Hydrangea hydrangea Achacha, a plant extract obtained from the pine fungus matsuhodo nuclei, from the leguminous genus kihagi The skin external preparation of Claim 11 containing at least 1 sort (s) selected from the plant extract obtained, and the plant extract obtained from the leguminous genus Scorpus. The skin external preparation according to any one of claims 1 to 15 , which is a cosmetic. The skin external preparation according to any one of claims 1 to 16 , which is for whitening. The skin external preparation according to any one of claims 1 to 17 , which is used for prevention or improvement of pigmentation due to exposure to ultraviolet rays. The skin external preparation according to any one of claims 1 to 18 , which is used for prevention or improvement of pigmentation abnormality involving cell inactivation of keratinocytes caused by melanin overtransport. The skin external preparation according to any one of claims 1 to 19 , which is in the form of an oil-in-water emulsifier.