JPH10168085A - Hydroquinone silane derivative and skin preparation for external use containing the same as active ingredient - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the new subject derivative that comprises a hydroquinone silane derivative, has melanin formation-inhibiting action, is excellent in skin- whitening effect that prevents skin pigmentation, stability and safety and is useful as a skin preparation for external use, a skin-whitening agent and a skin color-darkening inhibitor. SOLUTION: This novel compound is a hydroquinone silane derivative represented by formula I (R<1> is a divalent bridging group having at least two carbon atom; R<2> to R<4> are each a 1-8C organic group; X is H, a protecting group for a phenolic hydroxy group), has excellent melanin formation inhibitory action and skin-whitening action to prevent the formation of spots or freckles and skin pigmentation after sun burning with high stability and safety and is useful as a skin preparation for external use, 21 skin-whitening agent and a skin color-darkening inhibitor. This compound is prepared by hydrosilylation of monoalkenylhydroquinone of formula II (R<5> is an alkenyl of 2 or more carbon atoms) with a silane of' formula III.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention has an excellent melanin production inhibitory effect and is excellent in skin whitening effect for preventing skin pigmentation which occurs after spots, freckles or sunburn, etc., and has excellent stability and stability. A hydroquinone silane derivative which is excellent in safety and has good compatibility with the base component in a skin external preparation, and a skin external preparation which contains this as an active ingredient and is excellent in a melanin production inhibitory effect, a whitening effect, and a dullness preventing effect. Belongs to the technical field.

[0002]

2. Description of the Related Art In recent years, among skin care products, "whitening" has been particularly attracting attention. More specifically,
How to prevent the occurrence of skin spots, freckles and pigmentation on the skin after sunburn, etc., has become a major issue in current skin care. Furthermore, recently, great attention has been given to how to improve the "dullness" of the skin, which is said to be dull due to aging, fatigue, estrous cycle, and the like. First of all, there are some unclear points about the mechanism of occurrence of skin spots, freckles and pigmentation on the skin after sunburn, etc.
Generally, it is considered that a melanin pigment is formed in the skin due to hormonal abnormality or stimulation of ultraviolet rays from sunlight, and abnormal deposition in the skin is a major factor.

[0003] As a treatment or prevention method for such spots, freckles or pigmentation on the skin after sunburn, for example, substances that suppress the production of melanin (for example, vitamin C, etc.)
, A method of injecting glutathione or the like, and a method of topically applying kojic acid or cysteine as an active ingredient of a skin external preparation such as an ointment, cream or lotion. In the United States and Europe, hydroquinone preparations are used as pharmaceuticals. In addition, various skin external preparations for the purpose of whitening, such as resorcinol derivatives (JP-B-6-51619 and JP-A-6-56641), naphthoresorcinol (JP-A-5-92916) and An external preparation for skin containing a thioresorcin derivative (Japanese Patent Application Laid-Open No. Hei 6-329531) is known.

Although the cause of "dullness" is currently being studied intensely, skin aging due to aging and the like represented by poor subcutaneous blood circulation, melanin deposition, and a decrease in the turnover speed of the stratum corneum is generally observed. It has been clarified that the above factors seem to be complex, and it is particularly desired that a means for effectively preventing and treating this "dullness" be provided.

[0005]

As described above, "whitening" of the skin (in this application, "whitening"
Unless otherwise specified, the term "prevention and treatment of dullness" includes the concept of "melanin production" at least in the skin.
In other words, the provision of a means for effectively suppressing the production of melanin provides a significant step forward in skin care means for "whitening" the skin.

[0006] However, whitening means using a compound which is said to promote "whitening" tends to exhibit a very slow effect except for the case of using hydroquinone, and the whitening effect for these is not sufficient. I can not deny the missing side. On the other hand, although the whitening effect of hydroquinone has been recognized, there are many points to be considered in terms of the safety (irritation and sensitization) of hydroquinone itself,
In general, use is restricted (resorcinol derivatives, naphtoresorcinol and 4-thioresorcinol derivatives are also relatively irritating, and it is difficult to use them in large quantities to overcome the slowness of the effect. Is known to accompany it).

Further, the above compounds which can contribute to skin whitening tend to have poor compatibility with base components such as silicone oil used in external preparations for skin.
There is no denying that there are considerable restrictions on prescribing. The problem to be solved by the present invention is to find a new substance having properties overcoming the above-mentioned drawbacks and to provide an external preparation for skin containing the same.

[0008]

[Means for Solving the Problems] In view of such circumstances,
The present inventors have conducted intensive studies, and as a result, a specific hydroquinone silane derivative exerts a whitening effect by effectively suppressing melanin production more than hydroquinone, and has high safety, and is further used as a skin external preparation. The present inventors have found that they have excellent compatibility with the components used and can be blended in a large amount into a system containing a large amount of oily components such as an ultraviolet ray protective formulation, and have completed the present invention.

That is, the present inventor provides the following invention in the present application. In Claim 1, a hydroquinone silane derivative represented by the following formula (I) is provided.

Embedded image (Wherein, R ¹ represents a divalent linking group containing at least 2 carbon atoms, R ² , R ³ and R ⁴ may be the same or different, and an organic group having 1 or more and 8 or less carbon atoms) X represents a hydrogen atom or a protecting group for a phenolic hydroxyl group).

According to a second aspect of the present invention, there is provided a skin external preparation containing the hydroquinone silane derivative (I) according to the first aspect as an active ingredient.

In a third aspect, there is provided a whitening agent comprising the hydroquinone silane derivative (I) according to the first aspect as an active ingredient.

In a fourth aspect, there is provided a dulling inhibitor comprising the hydroquinone silane derivative (I) according to the first aspect as an active ingredient.

[0013]

Embodiments of the present invention will be described below. In the hydroquinone silane derivative (I) (hereinafter referred to as the derivative of the present invention) according to the present invention, “a divalent linking group containing at least two carbon atoms” R ¹ is
It is not particularly limited, specifically, not only an alkylene group,
An alkylene group containing an atom other than a carbon atom such as an oxygen atom, a nitrogen atom or a sulfur atom in the main chain, an alkylene group containing an arylene group such as a phenylene group in the main chain, a carbonyloxy group or a carbonyl group in the main chain. Alkylene group and the like. More specific examples of R ¹ include, for example, an ethylene group, a trimethylene group, a methylethylene group,
Tetramethylene group, 1-methyltrimethylene group, 2-methyltrimethylene group, 1,2-dimethylethylene group,
1,1-dimethylethylene group, ethylethylene group, pentamethylene group, 1-methyltetramethylene group, 2-methyltetramethylene group, 1,3-dimethyltrimethylene group, 1,2-dimethyltrimethylene group, 1-methylethylethylene group, 1-methyl-2-dimethylethylene group, 1-methyl-2-ethylethylene group, propylethylene group, isopropylethylene group, 2,2′-oxydiethylene group, 2,3′-oxy An ethylene trimethylene group, a 1'-methyl-2,2'-oxydiethylene group,
2′-methyl-2,2′-oxydiethylene group, 2,
4'-oxyethylenetetramethylene group, 2'-methyl-2,3'-oxyethylene trimethylene group, 1-methyl-2,3'-oxyethylene trimethylene group, 3'-
A methyl-2,3'-oxyethylene trimethylene group,
Examples include 1 ', 2'-dimethyl-2,2'-oxydiethylene group, 1', 1'-dimethyl-2,2'-oxydiethylene group, xylene group, cyclohexylene group, and decylene group. Of these divalent linking groups,
The derivative of the present invention, which is selected as R ¹ , has excellent whitening effect and has relatively few side reactions during its production. Group, trimethylene group, tetramethylene group, 1
-Methyltrimethylene group, 2-methyltrimethylene group,
A 2,3′-oxyethylene trimethylene group, 2′-methyl-2,3′-oxyethylene trimethylene group or the like is represented by R ¹
It is preferred to select

X represents a hydrogen atom or a protecting group. As the protecting group, a group generally used as a protecting group for a phenolic hydroxyl group can be selected, and it is not particularly limited, and a protecting group for a generally used phenolic hydroxyl group is shown. Examples of the protecting group for the phenolic hydroxyl group include alkyl groups such as methyl group, ethyl group, butyl group, isopropyl group, isobutyl group, tert-butyl group, cyclohexyl group and cyclopropylmethyl group;
Methoxymethyl group, benzyloxymethyl group, 2-trimethylsilylethoxymethyl group, 2-methoxyethoxymethyl group, methylthiomethyl group, phenylthiomethyl group, 2,2-dichloro-1,1-difluoroethyl group, tetrahydropyranyl group, Phenacyl group, p-bromophenacyl group, cyclopropylmethyl group, allyl group, benzyl group, o-nitrobenzyl group, 2,6-dimethylbenzyl group, 4-methoxybenzyl group, 2,6-dichlorobenzyl group, 4- ( Dimethylaminocarbonyl) ether groups such as benzyl group, 9-anthrylmethyl group, 4-picolyl group, heptafluoro-p-tolyl group and tetrafluoro-4-pyridyl group; silyl ethers such as trimethylsilyl group and tert-butyldimethylsilyl group Group; acetyl group, levroyl group, pivaloyl Groups, benzoyl groups, ester groups such as 9-florene carboxyl group; methoxycarboxyl group, 2,2,2-trichloroethoxy group, 2,2,2
Carbamates such as 2-trichloroethoxycarboxyl, vinylcarboxyl, benzylcarboxyl, allylcarboxyl; phosphinates such as dimethylphosphinyl, dimethylthiophosphinyl; methanesulfoxyl, p-toluenesulfur And sulfonates such as a foxyl group and a 2-formylbenzenesulfoxyl group.

When deprotection is carried out after a monoalkenylation reaction or a silylation reaction (described later) usually included in the derivative production process of the present invention, it is possible to sufficiently protect these reactions, X is, for example, a benzyl group, o
-Nitrobenzyl group, 2,6-dimethylbenzyl group, 4
-Methoxybenzyl group, 2,6-dichlorobenzyl group,
It is preferable to select a 4- (dimethylaminocarbonyl) benzyl group, a trichloroethyl group, or the like, but the protecting group that X can take is not limited thereto.

R ² , R ³ and R ⁴ each represent an organic group having 1 to 8 carbon atoms, such as a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group and a tert-butyl group. Alkyl groups such as pentyl group, hexyl group, heptyl group and octyl group; cycloalkyl groups such as cyclopentyl group, cyclohexyl group and cyclooctyl group; aryl groups such as phenyl group; aralkyl groups such as benzyl group; vinyl group and allyl An alkenyl group such as a group;
Examples thereof include, but are not limited to, alkyl fluoride groups such as 3,3,3-trifluoropropyl group. Among these organic groups, an organic group containing a phenyl group such as a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group or an aryl group or an aralkyl group can be selected. It is preferable because the whitening effect of the derivative is remarkable.

That is, an organosilyl group

Embedded image

[0018] Trimethylsilyl, dimethylethylsilyl, diethylmethylsilyl, diphenylmethylsilyl, dimethylphenylsilyl, dipropylmethylsilyl, diisopropylmethylsilyl, isopropyl-n-propylmethylsilyl, dimethylpropyl Silyl group, dimethylisopropylsilyl group, ethylmethylpropylsilyl group, ethylmethylisopropylsilyl group, dibutylmethylsilyl group, diisobutylmethylsilyl group, isobutyl-tert-butylmethylsilyl group,
n-butyl-tert-butylmethylsilyl group, n-butylisobutylmethylsilyl group, ditert-butylmethylsilyl group, dimethylbutylsilyl group, dimethylisobutylsilyl group, dimethyl-tert-butylsilyl group, butylethylmethylsilyl group, Isobutylethylmethylsilyl group,
tert-butylethylmethylsilyl group, butylmethylpropylsilyl group, isobutylmethylpropylsilyl group, isobutylmethylisopropylsilyl group, tert-butylmethylpropylsilyl group, tert-butylmethylisopropylsilyl group, ethylphenylmethylsilyl group, propylphenyl Examples thereof include a methylsilyl group, an isopropylphenylmethylsilyl group, a butylmethylphenylsilyl group, an isobutylmethylphenylsilyl group, and a tert-butylmethylphenylsilyl group.

The derivative of the present invention can be produced by the following means. That is, hydroquinone in which a protecting group is introduced into one of hydroquinone or a phenolic hydroxyl group is subjected to monoalkenylation by a method described below, whereby a monoalkenyl compound represented by the following formula (II):

[0020]

Embedded image [Wherein, R ⁵ represents a monovalent linking group containing at least 2 carbon atoms (corresponding to R ¹ which is a divalent linking group, and X is the same as described above)]

To obtain the monoalkenyl compound (II) and an organosilane represented by the following formula (III):

Embedded image (Wherein R ² , R ³ and R ⁴ are as defined above)

Can be produced by a hydrosilylation reaction. Examples of the monovalent bonding group R ⁵ include a vinyl group, an allyl group, an isopropenyl group,
-Butenyl group, 2-butenyl group, 3-butenyl group, 1-
Methyl-1-propenyl group, 1-methyl-2-propenyl group, 2-methyl-1-propenyl group, 2-methyl-3
-Propenyl group, 1-ethylethynyl group, 2-ethylethynyl group, 1-pentenyl group, 2-pentenyl group. 3-
Pentenyl group, 4-pentenyl group, 1-methyl-1-butenyl group, 1-methyl-2-butenyl group, 1-methyl-
3-butenyl group, 2-methyl-1-butenyl group, 2-methyl-2-butenyl group, 2-methyl-3-butenyl group,
3-methyl-1-butenyl group, 3-methyl-2-butenyl group, 3-methyl-3-butenyl group, 1,2-dimethyl-1-propenyl group, 1,1-dimethyl-2-propenyl group, 1 , 2-dimethyl-2-propenyl group, 1-ethyl-1-propenyl group, 1-ethyl-2-propenyl group, 1-propylvinyl group, 1-isopropylvinyl group, vinyloxyethyl group, allyloxyethyl group, 1
-Butynyloxyethyl group, 2-butynyloxyethyl group, 3-butynyloxyethyl group, 2-methyl-1-propynyloxyethyl group, 2-methyl-2-propynyloxyethyl group, 1-methyl-1 -Propynyloxyethyl group, 1-methyl-2-propynyloxyethyl group,
Examples include a hexynyl group, a cyclohexynyl group, and a decynyl group. The monovalent linking group R ⁵ is a group corresponding to the above-described divalent linking group R ^1, and a group suitable for selection also corresponds to the above-described divalent linking group R ¹ .

This monoalkenylation reaction can be selected from ordinary etherification reactions, for example, the synthesis method of Williamson et al. Using alkenyl halide,
Hurd et al. [J. Am. Chem. Soc, 52, 1700 (1930)
And a dehydration reaction with an alcohol using an acid or an alkali. Specifically, for example, the phenolic hydroxyl group of hydroquinone or one of hydroquinone is
Is a protecting group as described above, a hydroquinone derivative protected with the same protecting group (hereinafter sometimes referred to as hydroquinone, etc.) is converted to dimethylformamide, dimethylsulfoxide, dioxane, dimethylacetamide, N-methylpyrrolidone, N-acetylmorpholine, Dissolve or disperse in a polar solvent such as N-methylsuccinimide, HMPA, acetone, water, etc., a non-polar solvent dissolving hydroquinone or the like, or a mixture of these solvents, and add the compound represented by the formula R ⁵ -Y (where Y is fluorine, chlorine, bromine, halogen atom such as iodine; a halogen salt or hydroxyl trialkylammonium group such as bromide, R ⁵
Is the same as above)

Alkenyl derivative represented by the following formula, and adding a catalyst [for example, a mineral acid such as sulfuric acid and phosphoric acid; an organic acid such as p-toluenesulfonic acid; lithium hydroxide, sodium hydroxide, potassium hydroxide and sodium hydride Alkali such as;
Potassium carbonate, sodium carbonate, sodium bicarbonate,
A salt such as potassium hydrogencarbonate; a sodium alcoholate such as sodium methylate or sodium ethylate; an amine such as pyridine, DMPA, N-methylbenzylamine, etc.] under stirring at room temperature to 130 ° C under stirring. Can be

In this reaction, the molar ratio of the alkenyl derivative (R ⁵ -Y) to hydroquinone is 0.8: 1.
１ ： 1: 3 is preferable, and 0.9: 1 to 1: 2 is more preferable. The molar ratio of the alkenyl derivative to the hydroquinone derivative in which the phenolic hydroxyl group is protected by the protective group is preferably 1: 1 to 1: 3, and more preferably 1: 1 to 1: 3.
2.5 is more preferred.

When the molar ratio deviates from the above range, if the amount of hydroquinone or the like is small relative to the alkenyl derivative,
In the monoalkenylation reaction, impurities such as ether are liable to be generated. Conversely, if the amount of hydroquinone or the like is too large, a large amount of hydroquinone or the like remains after the reaction.

After the completion of the monoalkenylation reaction, an acid such as acetic acid, hydrochloric acid, sulfuric acid, phosphoric acid or the like, an alkali such as sodium hydroxide, lithium hydroxide or potassium hydroxide, or carbonic acid for neutralizing the catalyst of the reaction system. The reaction solvent can be distilled off by adding a salt such as sodium hydrogen, potassium hydrogen carbonate, sodium carbonate, potassium carbonate or the like, or the reaction solvent can be distilled off without neutralization.

The reaction product of the monoalkenylation reaction thus obtained contains a desired monoalkenyl compound (I
In addition to I), since there are salts at the time of monoalkenylation reaction and neutralization, as well as unreacted hydroquinone and dialkenyl compounds, a purification step for removing these by-products and the like can be performed. That is, for example, solvent extraction with a solvent that does not dissolve hydroquinone such as toluene and benzene or a non-polar solvent such as ethyl acetate, chloroform, dichloromethane, and methyl ethyl ketone, and further concentrating the extract, followed by methanol, ethanol, toluene, benzene, cyclohexane, etc. Can be used for recrystallization and the like.

In the above monoalkenylation reaction, when X is a protecting group instead of a hydrogen atom, and it is intended that the desired derivative of the present invention is deprotected (without deprotection, In addition, the derivative of the present invention exhibits a desired whitening effect, etc.), and the desired derivative of the present invention can be obtained by deprotecting the protecting group X by a generally known method. The timing of the deprotection may be before or after the hydrosilylation reaction. For this deprotection, a generally known method is used depending on the type of each protecting group.However, when deprotection is performed before the hydrosilylation reaction, an alkenyl group is used, and when deprotection is performed after this reaction, It is preferable to carry out the reaction under conditions that do not cause decomposition or conversion of the organosilyl group.

Next, the hydrosilylation reaction for producing the derivative of the present invention from the monoalkenyl compound (II) can be carried out by reacting the organosilane (III) with the monoalkenyl compound (II) in an organic solvent. it can. As the organic solvent used herein, an aromatic organic solvent such as toluene, benzene, or xylene is preferable, and the reaction is preferably performed at a high temperature, that is, at 70 ° C. to reflux temperature.
It is also possible to use a catalyst for promoting the hydrosilylation reaction, for example, a rhodium complex (Wilkin complex).
son complex), a ruthenium complex, a platinum complex, chloroplatinic acid, a platinum acid-based catalyst such as a vinylsiloxane platinum catalyst, or the like can be used as a catalyst. Among these catalysts,
In view of the availability, the yield, and the simplicity in the operation of the synthesis reaction, it is preferable to select a platinum acid catalyst such as chloroplatinic acid or a vinylsiloxane platinum catalyst.

The derivatives of the present invention thus produced may be oily to solid at room temperature. That is, in the derivative of the present invention, as the content of an aryl group such as a phenyl group in the substituent of the silyl group of R ² , R ³ and R ⁴ increases, the derivative tends to become solid. The derivative of the present invention thus produced not only has an excellent melanin production inhibitory effect, but also has excellent safety and stability, and has excellent compatibility with components used in external skin preparations such as silicone oil. ing.

That is, the skin external preparation containing the derivative of the present invention as an active ingredient can be prepared into various dosage forms and forms while having an excellent whitening effect. Larger quantities are also possible.
Therefore, an external preparation for skin containing the derivative of the present invention as an active ingredient will be described below.

As described later, the external preparation for skin containing the derivative of the present invention as an active ingredient is also expressed as a whitening agent or a dulling preventive agent in terms of its specific use. The “external preparation for skin of the present invention” includes all of the drugs in these specific categories. The external preparation for skin of the present invention contains at least one or more of the above-mentioned derivatives of the present invention.

The amount of the derivative of the present invention to be incorporated in the external preparation for skin of the present invention should be individually and specifically determined according to the specific use and other components, but is generally about 0.001% by weight of the external preparation for skin. % To 20.0% by weight, preferably 0.01% to 10.0% by weight, particularly preferably 0.1% to 7.0% by weight. If the amount of the external preparation for skin is less than 0.001% by weight, the whitening effect is poor, and if the amount exceeds 20.0% by weight, the increase in the whitening effect cannot be expected in proportion to the increase in the amount.

Thus, by incorporating the derivative of the present invention as an active ingredient, the skin external preparation of the present invention having an excellent whitening effect is provided. As described above, as a specific embodiment of the skin external preparation of the present invention, there can be firstly mentioned a "whitening agent" which directly utilizes its essential effect "melanin production inhibitory effect". This whitening agent aims to prevent and treat these skin phenomena by directly suppressing the production of melanin, which is one of the causes of spots, freckles, pigmentation after sunburn, etc. in the skin. It is a skin external preparation.

As the active ingredient in this whitening agent, the desired effect can be sufficiently exhibited only with the derivative of the present invention, but it is also possible to combine known active ingredients in combination with the derivative of the present invention. is there. For example, vitamin C, glutathione, hydroquinone, arbutin, kojic acid, magnesium phosphate ascorbate, glucoside ascorbate, caffeine, tannin, verapamil,
Known tranexamic acid or tranexamic acid derivatives, licorice extract, glabridine, hot water extract of fire thorn fruit, various crude drugs, tocopherol acetate, glycyrrhizic acid (including salts) or glycyrrhizic acid derivatives (including salts) It can be further combined with a whitening component to further improve the whitening effect.

Further, an ultraviolet absorbing agent can be added to the whitening agent of the present invention to impart an ultraviolet shielding effect. That is, for example, paraaminobenzoic acid (hereinafter abbreviated as PABA), PABA monoglycerin ester, N, N-dipropoxy PABA ethyl ester, N, N-diethoxy PABA ethyl ester, N, N-dimethyl PABA ethyl ester, N, N-dimethyl Paraaminobenzoic acid-based ultraviolet absorbers such as PABA butyl ester and N, N-dimethyl PABA tyl ester; anthranilic acid-based ultraviolet absorbers such as homomenthyl-N-acetylanthranilate; amyl salicylate, menthyl salicylate, homomenthyl salicylate, octyl salicylate , Phenyl salicylate, benzyl salicylate, p-isopropanol phenyl salicylate, etc .; salicylic acid ultraviolet absorbers; octylcinnamate, ethyl-4-isopropylcinnamate Methyl-2,5-diisopropyl cinnamate, ethyl-2,4-diisopropyl cinnamate, methyl-2,4-diisopropyl cinnamate,
Propyl-p-methoxycinnamate, isopropyl-
p-methoxycinnamate, isoamyl-p-methoxycinnamate, octyl-p-methoxycinnamate (2-ethylhexyl-p-methoxycinnamate),
2-ethoxyethyl-p-methoxycinnamate, cyclohexyl-p-methoxycinnamate, ethyl-α-
Cinnamic acid ultraviolet absorbers such as cyano-β-phenylcinnamate, 2-ethylhexyl-α-cyano-β-phenylcinnamate, glyceryl mono-2-ethylhexanoyl-diparamethoxycinnamate; 2,4-dihydroxy Benzophenone, 2,2′-dihydroxy-4-methoxybenzophenone, 2,2′-dihydroxy-4,
4'-dimethoxybenzophenone, 2,2 ', 4,4'
-Tetrahydroxybenzophenone, 2-hydroxy-
4-methoxybenzophenone, 2-hydroxy-4-methoxy-4′-methylbenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonate, 4
-Phenylbenzophenone, 2-ethylhexyl-4 '
-Phenyl-benzophenone-2-carboxylate,
2-hydroxy-4-n-octoxybenzophenone,
Benzophenone-based ultraviolet absorbers such as 4-hydroxy-3-carboxybenzophenone; 3- (4′-methylbenzylidene) -d, 1-camphor, 3-benzylidene-
d, 1-Camphor, urocanic acid, urocanic acid ethyl ester, 2-phenyl-5-methylbenzoxazole, 2,2'-hydroxy-5-methylphenylbenzotriazole, 2- (2'-hydroxy-5'- tert-
Octylphenyl) benzotriazole, 2- (2'-
Hydroxy-5'-methylphenylbenzotriazole, dibenzalazine, dianisoylmethane, 4-methoxy-4'-tert-butyldibenzoylmethane, 5-
UV absorbers such as (3,3-dimethyl-2-norbornylidene) -3-pentan-2-one; UV-blockers such as titanium dioxide powder; and plant extracts having a UV-shielding effect such as aloe extract. It can be incorporated into the whitening agent of the present invention.

Further, a humectant may be added to the whitening agent of the present invention to impart a moisturizing effect to the whitening agent of the present invention.
That is, as the humectant, for example, polyethylene glycol, propylene glycol, glycerin, 1,3-butylene glycol, xylitol, sorbitol, maltitol, chondroitin sulfate, hyaluronic acid, mucoitin sulfate, caronic acid, atelocollagen, cholesteryl-12-hydroxysteare Rate, sodium lactate,
Bile salts, dl-pyrrolidone carboxylate, short-chain soluble collagen, diglycerin (EO) PO adduct, Izayobara extract, Achillea millefolium extract, melilot extract, etc. are blended in the whitening agent of the present invention. A moisturizing effect can be imparted to the inventive whitening agent.

In addition, vitamin A, vitamin B ₁ , vitamin B ₂ , vitamin B ₆ , vitamin E or derivatives thereof, pantothenic acid or derivatives thereof, vitamins such as biotin and skin nutritional supplements, and amino acids such as glycine and alanine; Neutral amino acids such as valine, leucine, isoleucine, serine, threonine, tryptophan, cystine, cysteine, methionine, proline, and hydroxyproline; acidic amino acids such as aspartic acid, glutamic acid, asparagine, and glutamine; arginine, histidine, lysine, and hydroxylysine Can be added to the whitening agent of the present invention. Further, as amino acid derivatives, for example, acyl sarcosine sodium (lauroyl sarcosine sodium), acyl glutamate, a Le β- alanine sodium, glutathione, and pyrrolidone carboxylic acid can be incorporated into the present invention lightening agent.

Further, as another embodiment of the external preparation for skin of the present invention, it can be in the form of an "anti-dulling agent". This anti-dulling agent of the present invention is a skin external preparation capable of preventing and preventing “dullness” from the viewpoint of suppressing the deposition of melanin by blending the derivative of the present invention as an active ingredient. Therefore, in addition to the derivative of the present invention, other well-known medicinal components can be added to the dulling inhibitor of the present invention in accordance with the above-mentioned present mechanism of “dullness”.

In addition to these medicinal ingredients which are considered to be involved in the mechanism of the occurrence of "dullness", similar to the above-mentioned whitening agents (the above-mentioned components may be added to the dulling inhibitor of the present invention. There are no contraindicated components), for example, an ultraviolet absorber, a humectant, a vitamin, a skin nutrient, an amino acid, an amino acid derivative and the like can be appropriately incorporated into the dullness inhibitor of the present invention.

The skin external preparation of the present invention (including the whitening agent of the present invention and the dulling inhibitor of the present invention) is usually used in order to incorporate the derivative of the present invention having good compatibility with base components such as silicone oil. It can be easily prepared into various dosage forms and forms by the method. That is, the dosage form and form that the external preparation for skin of the present invention can take is not particularly limited, and the external preparation for skin of the present invention can be prepared into almost all dosage forms and forms that the external preparation for skin can take. is there. For example, it can be in the form of cream, ointment, gel, lotion, emulsion, stick, pack, solution with an organic solvent, and the like.

That is, in the external preparation for skin of the present invention, for example, powder components, liquid fats and oils, solid fats and oils, waxes, hydrocarbons, higher fatty acids, higher alcohols, esters, silicones,
Fluorinated oil, anionic surfactant, cationic surfactant,
Amphoteric surfactants, nonionic surfactants, water-soluble polymer compounds, thickeners, coating agents, sequestering agents, lower alcohols, polyhydric alcohols, sugars, amino acids, organic amines, synthetic resin emulsions, pH Regulators, antioxidants,
One or two or more antioxidant aids, fragrances, water and the like can be appropriately added as needed.

Specifically, examples of the powder component include talc, kaolin, mica, sericite (sericite), muscovite, phlogopite, synthetic mica, biotite, biotite, lithia mica,
Vermiculite, magnesium carbonate, calcium carbonate, aluminum silicate, barium silicate, calcium silicate, magnesium silicate, strontium silicate,
Metal tungstate, magnesium, silica, zeolite, barium sulfate, calcined calcium sulfate (baked gypsum), calcium phosphate, fluorapatite, hydroxyapatite, ceramic powder, metal soap (zinc myristate, calcium palmitate, aluminum stearate), nitriding Inorganic powders such as boron; polyamide resin powder (nylon powder), polyethylene powder, polymethyl methacrylate powder, polystyrene powder, copolymer resin powder of styrene and acrylic acid, benzoguanamine resin powder, polytetrafluoroethylene powder, cellulose powder Inorganic powders such as titanium dioxide and zinc oxide; inorganic red pigments such as iron oxide (iron oxide) and iron titanate;
Inorganic brown pigments such as iron oxide; inorganic yellow pigments such as yellow iron oxide and loess; inorganic black pigments such as black iron oxide, carbon black and low titanium oxide; inorganic purple pigments such as mango violet and cobalt violet. Inorganic green pigments such as chromium oxide, chromium hydroxide, and cobalt titanate;
Inorganic blue pigments such as navy blue and the like; pearl pigments such as titanium oxide coated mica, titanium oxide coated bismuth oxychloride, titanium oxide coated talc, colored titanium oxide coated mica, bismuth oxychloride, fish scale foil, and metals such as aluminum powder and copper powder. Powder pigments: Red 201, Red 202, Red 204, Red 205, Red 220, Red 226, Red 228
Organic pigments such as No. 4, Red No. 405, Orange No. 203, Orange No. 204, Yellow No. 205, Yellow No. 401, Blue No. 404; Red No. 3, Red No. 104, Red No. 106, Red No. 22
No. 7, Red No. 230, Red No. 401, Red No. 505, Orange No. 205, Yellow No. 4, Yellow No. 5, Yellow No. 202, Yellow No. 203, Green No. 3, Blue No. 1, etc., zirconium, barium or aluminum lake And other organic pigments. These powder components may be directly incorporated into the external preparation for skin of the present invention. However, silicone treatment with methyl hydrogen polysiloxane, a silane coupling agent, or the like; metal soap treatment; Hydrophobic treatment such as fluorine treatment of perfluoroalkylsilane may be performed. In addition, natural pigments such as chlorophyll and β-carotene may be incorporated into the external preparation for skin of the present invention.

Examples of liquid fats and oils include avocado oil, camellia oil, turtle oil, macadamia nut oil, corn oil, mink oil, olive oil, rapeseed oil, egg yolk oil, sesame oil, persic oil, wheat germ oil, sasanqua oil, castor oil, Linseed oil, safflower oil, cottonseed oil, eno oil, soybean oil, peanut oil, teaseed oil, kaya oil, rice bran oil, sinagiri oil, Japanese kiri oil, jojoba oil, germ oil, triglycerin,
Glycerin trioctanoate, glycerin triisopalmitate and the like can be incorporated into the skin external preparation of the present invention.

Examples of solid fats and oils include cocoa butter, coconut oil, horse fat, hardened coconut oil, palm oil, tallow, sheep butter, hardened tallow, palm kernel oil, lard, beef bone oil, mokuro kernel oil, hardened oil , Beef tallow, mocro, hardened castor oil, and the like can be incorporated into the skin external preparation of the present invention.

Examples of waxes include beeswax, candelilla wax, cotton wax, carnauba wax, bayberry wax,
Ibota wax, whale wax, montan wax, bran wax, lanolin, kapok wax, lanolin acetate, liquid lanolin, sugar cane wax, lanolin fatty acid isopropyl, hexyl laurate, reduced lanolin, jojoba wax, hard lanolin, shellac wax, POE lanolin alcohol ether, POE lanolin alcohol acetate , POE cholesterol ether, lanolin fatty acid polyethylene glycol, POE hydrogenated lanolin alcohol ether, and the like can be blended in the skin external preparation of the present invention.

As the hydrocarbon oil, for example, liquid paraffin, ozokerite, squalene, pristane, paraffin, ceresin, squalane, vaseline, microcrystalline wax, soft liquid paraffin, and the like can be added to the skin external preparation of the present invention.

As higher fatty acids, for example, lauric acid,
Myristic acid, palmitic acid, stearic acid, behenic (behenic) acid, oleic acid, 12-hydroxystearic acid, undecylenic acid, tolic acid, isostearic acid, linoleic acid, linoleic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) ) And the like can be incorporated into the skin external preparation of the present invention.

Examples of the higher alcohol include linear alcohols such as lauryl alcohol, cetyl alcohol, stearyl alcohol, behenyl alcohol, myristyl alcohol, oleyl alcohol, and cetostearyl alcohol; monostearyl glycerin ether (bacyl alcohol), 2-decyltetradecinol , Lanolin alcohol, cholesterol, phytosterol, hexyl decanol, isostearyl alcohol, branched chain alcohols such as octyl dodecanol and the like can be incorporated into the skin external preparation of the present invention.

Examples of synthetic ester oils include isopropyl myristate, cetyl octanoate, octyl dodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, hexyl decyl dimethyl octanoate, lactic acid Cetyl, myristyl lactate, lanolin acetate,
Isocetyl stearate, isocetyl isostearate, cholesteryl 12-hydroxystearate, di-
Ethylene glycol 2-ethylhexylate, dipentaerythritol fatty acid ester, monoisostearic acid N
Alkyl glycol, neopentyl glycol dicaprate, diisostearyl malate, glycerin di-2-heptylundecanoate, trimethylolpropane tri-2-ethylhexylate, trimethylolpropane triisostearate, pentaneerythritol tetra-2-ethylhexylate Glycerin tri-2-ethylhexylate, trimethylolpropane triisostearate, cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, glycerin trimyristate, tri-2-heptylundecanoic acid glyceride, castor oil fatty acid methyl ester, Oleic acid oil, cetostearyl alcohol, acetoglyceride, palmitic acid 2-
Heptylundecyl, diisobutyl adipate, N-lauroyl-L-glutamic acid-2-octyldodecyl ester, di-2-heptylundecyl adipate, ethyl laurate, di-2-ethylhexyl sebacate, 2-hexyldecyl myristate , 2-hexyldecyl palmitate, 2-hexyldecyl adipate, diisopropyl sebacate, 2-ethylhexyl succinate, ethyl acetate, butyl acetate, amyl acetate, triethyl citrate and the like may be compounded in the skin external preparation of the present invention. it can.

Examples of the silicone include dimethylpolysiloxane, methylphenylpolysiloxane, methylhydrogenpolysiloxane, fluorine-modified silicone, fluorine-modified methylphenylpolysiloxane, alkyl-modified silicone, polyether-modified silicone, amino-modified silicone, decamethylcyclopentane Polysiloxane,
Cyclic polysiloxane such as dodecamethylcyclohexapolysiloxane, tetramethyltetrahydrogencyclotetrapolysiloxane, silicone resin forming a three-dimensional network structure, high-molecular dimethylpolysiloxane,
Silicone rubber and the like such as high molecular weight methylphenylpolysiloxane can be incorporated into the skin external preparation of the present invention. Since the derivative of the present invention, which is an active ingredient of the external preparation for skin of the present invention, has particularly good compatibility with the silicone exemplified here, use the external preparation for skin of the present invention for the form and dosage form in which the silicone is compounded. Is particularly preferred.

Examples of the anionic surfactant include a soap base, a fatty acid soap such as sodium laurate and sodium palmitate, sodium lauryl sulfate,
Higher alkyl sulfates such as lauryl sulfate K, PO
Alkyl ether sulfates such as E-lauryl sulfate triethanolamine and POE sodium lauryl sulfate;
N-acyl sarcosine acids such as sodium lauroyl sarcosine, N-myristoyl-N-methyl taurine sodium, coconut oil fatty acid methyl tauride sodium, higher fatty acid amide sulfonates such as sodium lauryl methyl tauride, POE sodium oleyl ether phosphate, Phosphate ester salts such as POE stearyl ether phosphoric acid, sodium di-2-ethylhexyl sulfosuccinate, sodium monolauroyl monoethanolamide polyoxyethylene sodium sulfosuccinate, sulfosuccinates such as sodium lauryl polypropylene glycol sulfosuccinate, and linear dodecylbenzenesulfonic acid Sodium, alkyl benzene sulfonic acid salts such as addecyl benzene sulfonic acid triethanolamine, addecyl benzene sulfonic acid, - lauroyl monosodium glutamate, disodium N- stearoyl glutamate,
N-acyl glutamates such as monosodium N-myristoyl-L-glutamate; higher fatty acid ester sulfates such as hydrogenated coconut fatty acid sodium glycerin sulfate; sulfated oils such as funnel oil; POE alkyl ether carboxylic acid; POE alkyl allyl Ether carboxylate, α-olefin sulfonate, higher fatty acid ester sulfonate, secondary alcohol sulfate, higher fatty acid alkylolamide sulfate, sodium lauroyl monoethanolamidosuccinate, N-palmitoyl aspartate ditriethanol Amine, sodium caseinate and the like can be added to the skin external preparation of the present invention.

Examples of the cationic surfactant include alkyltrimethylammonium salts such as stearyltrimethylammonium chloride, cetyltrimethylammonium chloride and lauryltrimethylammonium chloride, distearyldimethylammonium dialkyldimethylammonium chloride, and poly (N, N′-chloride). Alkylpyridinium salts such as dimethyl-3,5-methylenepiperidinium) and cetylpyridinium chloride; alkyl quaternary ammonium salts; alkyldimethylbenzylammonium salts; alkylisoquinolinium salts; dialkylmorphonium salts;
OE alkylamines, alkylamine salts, polyamine fatty acid derivatives, amyl alcohol fatty acid derivatives, benzalkonium chloride, benzethonium chloride and the like can be incorporated into the skin external preparation of the present invention.

Examples of the amphoteric surfactant include 2-undecyl-N, N, N- (hydroxyethylcarboxymethyl) -2-imidazoline sodium and 2-cocoyl-
Imidazoline amphoteric surfactants such as 2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt; 2-heptadecyl-N-carboxymethyl-N
Betaine-based surfactants such as hydroxyethylimidazolinium betaine, lauryldimethylaminoacetate betaine, alkylbetaine, amidobetaine and sulfobetaine; lauryl dimethylamine oxide, stearyl dimethylamine oxide, 2-decyltetradecyl dimethylamine oxide and the like Amine oxide and the like can be incorporated into the skin external preparation of the present invention.

Examples of the lipophilic nonionic surfactant include sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, and pentane Diglycerol sorbitan-2-ethylhexylate,
Sorbitan fatty acid esters such as diglycerol sorbitan tetra-2-ethylhexylate, glycerin mono-cottonseed oil, glycerin monoerucate, glycerin sesquioleate, glyceryl monostearate, α, α ′
Glycerin polyglycerin fatty acids such as glycerin pyroglutamate oleate and glyceryl monostearate, propylene glycol fatty acid esters such as propylene glycol monostearate, hydrogenated castor oil derivatives, glycerin alkyl ether, etc. Can be blended.

Examples of the hydrophilic nonionic surfactant include POE sorbitan fatty acid esters such as POE sorbitan monooleate, POE-sorbitan monostearate, POE-sorbitan monooleate, POE-sorbitan tetraoleate; and POE-sorbit. Monolaurate, POE-Sorbit monooleate, POE
POE sorbitol fatty acid esters such as sorbit pentaoleate, POE-sorbitol monostearate; POE glycerin fatty acid esters such as POE-glycerin monostearate, POE-glycerin monoisostearate, POE-glycerin triisostearate; POE monooleate, POE distearate,
POE fatty acid esters such as POE monodioleate and ethylene glycol cysteate; POE alkyl ethers such as POE lauryl ether, POE oleyl ether, POE stearyl ether, POE behenyl ether, POE2-octyldodecyl ether, POE cholestanol ether; POE octyl POE alkyl phenyl ethers such as phenyl ether, POE nonyl phenyl ether and POE dinonyl phenyl ether; Pluronic types such as bruronic; POE · P
OP cetyl ether, POE.POP 2-decyltetradecyl ether, POE.POP monobutyl ether,
POE / POP hydrogenated lanolin, POE / POP alkyl ethers such as POE / POP glycerin ether; tetra-POE / tetra-POP ethylenediamine condensates such as tetronic; POE castor oil, POE-hardened castor oil, POE-hardened castor oil monoiso Stearate, POE
POE castor oil-hardened castor oil derivatives such as hydrogenated castor oil triisostearate, POE-hardened castor oil monopyroglutamic acid monoisostearate diester, POE-hardened castor oil-maleic acid; P such as POE sorbitol beeswax
OE beeswax lanolin derivatives; alkanolamides such as coconut oil fatty acid diethanolamide, lauric acid monoethanolamide, fatty acid isopropanolamide, PO
E Propylene glycol fatty acid ester, POE alkylamine, POE fatty acid amide, sucrose fatty acid ester, POE nonylphenylformaldehyde condensate, alkylethoxydimethylamine oxide, trioleyl phosphoric acid, etc. can be blended in the skin external preparation of the present invention. .

Examples of natural water-soluble polymers include gum arabic, tragacanth gum, galactan, guar gum,
Carob gum, karaya gum, carrageenan, pectin,
Plant-based polymers such as agar, quince seed (quince), alge colloid (gasso extract), starch (rice, corn, potato, wheat), glycyrrhizic acid; microbial polymers such as xanthan gum, dextran, succinoglucan, pullulan; Animal-based macromolecules such as collagen, casein, albumin, and gelatin can be incorporated into the skin external preparation of the present invention.

Examples of the semi-synthetic water-soluble polymer include starch-based polymers such as carboxymethyl starch and methylhydroxypropyl starch; methylcellulose, nitrocellulose, ethylcellulose, methylhydroxypropylcellulose, hydroxyethylcellulose, sodium cellulose sulfate, and hydroxypropylcellulose. ,
Cellulosic polymers such as sodium carboxymethylcellulose (CMC), crystalline cellulose, and cellulose powder;
Alginate polymers such as sodium alginate and propylene glycol alginate can be incorporated into the skin external preparation of the present invention.

Examples of the synthetic water-soluble polymer include vinyl polymers such as polyvinyl alcohol, polyvinyl methyl ether, polyvinyl pyrrolidone and carboxyvinyl polymer (Carbopol);
Polyoxyethylene polymers such as 0000, 4,000,000 and 600,000; polyoxyethylene polyoxypropylene copolymer copolymer polymers, sodium polyacrylate, polyethyl acrylate, polyacrylamide, etc. Acrylic polymer; polyethylene imine,
A cationic polymer or the like can be incorporated into the skin external preparation of the present invention.

As the inorganic water-soluble polymer, for example, bentonite, A1Mg silicic acid (Vegum), laponite, hectorite, silicic anhydride and the like can be incorporated into the skin external preparation of the present invention.

As the thickener, for example, dextrin, sodium pectate, locust bean gum, tamarind gum, dialkyldimethylammonium cellulose sulfate and the like can be blended in the skin external preparation of the present invention.

Examples of the sequestering agent include 1-hydroxyethane-1,1-diphosphonic acid, 1-hydroxyethane-1,1-diphosphonic acid tetrasodium salt,
Disodium edetate, trisodium edetate, tetrasodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, phosphoric acid,
Citric acid, ascorbic acid, succinic acid, edetic acid, and the like can be added to the skin external preparation of the present invention.

As the lower alcohol, for example, methanol, ethanol, propanol, isopropanol, isobutyl alcohol, tert-butyl alcohol and the like can be incorporated into the skin external preparation of the present invention.

The monosaccharides include, for example, tri-carbon sugars such as D-glyceryl aldehyde and dihydroxyacetone; tetra-carbon sugars such as D-erythrose, D-erythrulose, D-threose and erythritol; L-arabinose, D-xylose, L Pentoses such as lyxose, D-arabinose, D-ribose, D-ribulose, D-xylulose, L-xylulose; D-glucose, D-talose, D-
Bucose, D-galactose, D-fructose, L
Hexoses such as galactose, L-mannose and D-tagatose; heptose such as aldoheptose and heppulose;
Octanoses such as octulose; 2-deoxy-D-ribose, 6-deoxy-L-galactose, 6-deoxy-
Deoxy sugars such as L-mannose; D-glucosamine, D
-Uronic acids such as galactosamine, sialic acid, aminouronic acid, muramic acid, uronic acids such as D-glucuronic acid, D-mannuronic acid, L-guluronic acid, D-galacturonic acid, L-iduronic acid, etc. It can be incorporated into the composition.

As the oligosaccharide, for example, sucrose, guntianose, umbelliferose, lactose, planteose, isorikunoses, α, α-trehalose, raffinose, liqunoses, umbilisin, stachyose verbascose and the like can be used for the external skin of the present invention. It can be incorporated into the composition.

Examples of polysaccharides include cellulose, quince seed, chondroitin sulfate, starch, galactan, dermatan sulfate, glycogen, gum arabic, heparan sulfate, hyaluronic acid, tragacanth gum, keratan sulfate, chondroitin, xanthan gum, mucoitin sulfate, guar gum, dextran, Keratosulfuric acid, locust bean gum, succinoglucan, caronic acid and the like can be incorporated into the skin external preparation of the present invention.

Examples of the organic amine include monoethanolamine, diethanolamine, triethanolamine, morpholine, triisopropanolamine, 2-amino-2-methyl-1,3-propanediol, and 2-amino-2-methyl-1-methylamine. Propanol and the like can be incorporated into the skin external preparation of the present invention.

As the synthetic resin emulsion, for example, an acrylic resin emulsion, a polyethyl acrylate emulsion, an acrylic resin solution, a polyacryl alkyl ester emulsion, a polyvinyl acetate resin emulsion and the like can be blended in the skin external preparation of the present invention.

As the pH adjuster, for example, a buffer such as lactic acid-sodium lactate and citric acid-sodium citrate can be incorporated into the external preparation for skin of the present invention.

As antioxidants, for example, tocopherols, dibutylhydroxytoluene, butylhydroxyanisole, gallic esters and the like can be incorporated into the skin external preparation of the present invention.

Examples of the antioxidant aid include phosphoric acid, citric acid, ascorbic acid, maleic acid, malonic acid, succinic acid, fumaric acid, kephalin, hexametaphosphate, phytic acid, ethylenediaminetetraacetic acid, etc. It can be incorporated into an external preparation.

The specific form, dosage form and the like of the skin external preparation of the present invention will be described in the following examples.

[Synthesis Example 1]

[1] Synthesis of monoallyl hydroquinone 44 g of hydroquinone was dissolved in 500 ml of acetone.
58 g of potassium carbonate was added, and the mixture was heated under reflux. 48.4 g of allyl bromide was gradually added dropwise thereto, and the mixture was heated under reflux to cause a reaction. The mixture was extracted three times with 150 ml of benzene, and the organic phase was washed with water. It was dried over sodium sulfate, filtered off and concentrated under reduced pressure. The obtained residue (40.3 g) was purified by silica gel column chromatography [Wakogel C-200, hexane-hexane / toluene-MEK / toluene]. The desired monoallylhydroquinone was obtained in a yield of 22 g. The obtained monoallyl hydroquinone was analyzed by the methods (1) and (2).

(1) GC analysis method The obtained monoallylhydroquinone was adjusted to a 1% THF solution to prepare a sample solution, which was subjected to gas chromatography [column: HP-1, 0.2 mm × 25 mm, temperature rise;
The analysis was carried out under the conditions of C. to 260.degree. C., 8.degree. C./min, carrier gas and flow rate; helium, 50 ml / min., Detector: FID). The results are shown in FIG.

(2) GC / MS Analysis GC / MS analysis of 5890A gas chromatograph / MSD (Hullet Packard) was performed. GC under analytical conditions of gas chromatograph [column; HP-1, 0.2 mm × 25 mm, temperature rise; 100 ° C. to 260 ° C., 8 ° C./min, carrier gas and flow rate; helium, 1 ml / min, detector; FID) / MS analysis showed a retention time of 6.4.
Is the molecular ion peak (M + m / e)
Was confirmed to be 150. The results are shown in FIG. In addition, when hydroquinone was measured under the same conditions, a peak at a retention time of 5.1 minutes was observed, and it was confirmed that 110 had a molecular ion peak (M + m / e).

[2] Synthesis of 4- [3- (trimethylsilyl) propoxy] phenol 15 g of monoallyl hydroquinone obtained above
Was dissolved in 100 ml of toluene, 10 g of trimethylhydrosilane was added, and a chloroplatinic acid catalyst was added.
Reacted for minutes. After air cooling at room temperature, 3 g of activated carbon was added to adsorb the catalyst, the activated carbon was filtered off, and the residue obtained by concentration was purified by silica gel column chromatography [Wakogel C-200, toluene]. 15.2 g of hydroquinonesilane derivative (4- [3- (trimethylsilyl) propoxy] phenol) was obtained. The obtained silane derivative was analyzed by the following method.

(1) GC / MS analysis method GC / MS analysis of 5890A gas chromatograph / MSD (Hullet Packard) was performed. Gas chromatographic method [column: HP-1, 0.2 mm × 25 mm, temperature rise; 100 ° C. to 260 ° C., 8 ° C./min, carrier gas and flow rate; helium, 1 ml / min, detector; FID) GC / MS analysis showed a retention time of 8.9.
The observed peak at 208 is a molecular ion peak (M
⁺ m / e).

Synthesis Example 2 Synthesis of 4- [3- (dimethylethylsilyl) propoxy] phenol 15 g of monoallylhydroquinone obtained in Synthesis Example 1 was dissolved in 100 ml of toluene, and 12 g of dimethylethylhydrosilane was added thereto. Thereafter, a salt platinum acid catalyst was added, and 90
The reaction was carried out at 30 ° C for 30 minutes. After air cooling at room temperature, 3g of activated carbon
In addition, after adsorbing the catalyst, the mixture was filtered off and concentrated, and the resulting residue was subjected to silica gel column chromatography [Wakogel C.
-200, toluene] to give 16.1 g of the desired hydroquinonesilane derivative (4- [3- (dimethylethylsilyl) propoxy] phenol).

Synthesis Example 3 Synthesis of 4- {2- [3- (trimethylsilyl) propoxy] ethoxy} phenol 50 g of hydroquinone was dissolved in 500 ml of acetone.
30 g of potassium carbonate was added, and the mixture was heated under reflux. In addition, 2
After 60 g of-(2-propenoxy) ethyl bromide was gradually added dropwise and reacted, the mixture was air-cooled at room temperature and concentrated.
This was extracted with ethyl acetate, washed three times with purified water, and the organic phase was dried over magnesium sulfate. After filtration, the filtrate was concentrated, and the obtained residue was recrystallized from methanol to obtain 51 g of the desired monoalkynyl hydroquinone (4- [2- (2-propenoxy) ethoxy] phenol).

The obtained 4- [2- (2-propenoxy)
17 g of [ethoxy] phenol in 120 ml of toluene
After adding 13 g of trimethylhydroxysilane, a platinum salt catalyst was added, and the mixture was reacted at 90 ° C. for 30 minutes.
After air cooling at room temperature, 2 g of activated carbon was added, the catalyst was adsorbed, filtered off and concentrated, and the residue obtained was concentrated by silica gel column chromatography [Wakogel C-200, toluene].
And the desired hydroquinone silane derivative (4-
17.5 g of {2- [3- (trimethylsilyl) propoxy] ethoxy} phenol) was obtained.

[Synthesis Example 4] Synthesis of 4- [3- (dimethylphenylsilyl) propoxy] phenol 1 g of monoallylhydroquinone obtained in Synthesis Example 1 was dissolved in 3 ml of toluene.
After adding g, a salt platinic acid catalyst was added and reacted at 90 ° C. for 30 minutes. After air cooling at room temperature, the activated carbon is
The catalyst was adsorbed on activated carbon, filtered off, concentrated and the residue obtained was purified by silica gel column chromatography [Wakogel C-200, toluene] to give the desired hydroquinone silane derivative (4 [3- 1.2 g of (dimethylphenylsilyl) propoxy] phenol) were obtained.

Test Example A test was conducted to inhibit the activity of tyrosinase, an enzyme essential for melanin production, using the derivative of the present invention synthesized in the above synthesis example. (1) Tyrosinase activity inhibition test (Test method) [Preparation of reagent]

L-DOPA solution 10 mg of L-DOPA (special reagent grade) was dissolved at the time of use with 20 ml of 0.1 M phosphate buffer at the time of use, and 0.05% of L-DOPA was dissolved.
The solution was used. Tyrosinase solution mushroom tyrosinase (50,000 units / 1
1.7 mg protein (manufactured by SIGMA) 11.7 mg
Was dissolved in 25 ml of distilled water to give a 2,000 unit / ml solution. The pH was adjusted to 6.8 by a conventional 0.1 M phosphate buffer method.

[Preparation of Sample Solution] Each sample shown in Table 1 described below was diluted with ethanol to three levels of concentration to obtain a sample solution.

[Test Method] The activity of tyrosinase was measured using P
The method was carried out by slightly modifying the method of Omerantz, using L-DOPA (special reagent grade) as a substrate, and measuring the absorbance at 475 nm based on the reaction product dopachrome. That is, L-DOPA solution 1.0 ml
And 1.8 ml of phosphate buffer, and add 0.1 ml of sample solution
ml was added. Next, 0.1 ml of a tyrosinase solution was added and mixed, and reacted at room temperature for 1.5 minutes. About this, a spectrophotometer (Spectrophotot manufactured by Hitachi, Ltd.)
The absorbance at 475 nm was measured using an O.T. As a reagent blank, 1.0 ml of distilled water was used instead of the L-DOPA solution, and 1.8 ml of a phosphate buffer and 0.1 ml of a sample solution were used.
1 ml was added and mixed, and the same procedure was followed to measure the absorbance, and the value was defined as T '.

The control was L-DOPA solution 1.0
0.1 ml of ethanol instead of the sample solution was added to 1.8 ml of the phosphate buffer and 1.8 ml of the phosphate buffer. As a control reagent blank, 1.0 ml of distilled water was used instead of the L-DOPA solution, and 1.8 ml of a phosphate buffer and 0.1 ml of ethanol were added thereto. . The tyrosinase activity inhibition rate at each sample concentration was calculated by the following formula, and the horizontal axis of the semilogarithmic graph was the sample concentration (log), and the vertical axis was the activity inhibition rate. From this graph, the tyrosinase activity 50% inhibition concentration (IC
0) was determined. In addition, T, T ', C, and C' were measured three times, and the average value of each was used. Tyrosinase activity inhibition rate (%) = 100 × [1- (T−
T ') / (CC')]

[Evaluation Method] The IC 50 of each drug was determined, and the tyrosinase activity inhibitory effect of the derivative of the present invention was examined based on the following criteria. (Criterion criteria) A: IC 50 is less than 10 mM. ：: IC 50 is 10 mM or more and less than 100 mM. Δ: IC 50 is 100 mM or more and less than 1 M. X: IC50 is 1M or more or no inhibition.

Table 1 shows the results.

[Table 1]

As is evident from Table 1, the derivative of the present invention can be used at a very low concentration (existing whitening components such as hydroquinone, 4-n-butylresorcinol and 4- (methylthio)).
(In comparison to resorcinol and naphtrezosinol) were found to inhibit the activity of tyrosinase, a major factor in the production of melanin in the skin. In particular, it is extremely surprising that a superior tyrosinase activity inhibitory effect was recognized as compared with hydroquinone, which is known as an excellent whitening component.

The results show that the external preparation for skin containing the derivative of the present invention as an active ingredient is an extremely excellent whitening agent which prevents or treats spots, freckles, pigmentation after sunburn caused by the production of melanin in the skin. It has been found that it can be in the form of an agent. In addition, it has been found that even if the production of melanin in the skin is not favorable, it can take a form as a "dullness" inhibitor which is one of the factors.

Hereinafter, the skin external preparation of the present invention (solubilized cosmetic)
And the drug efficacy tests (whitening effect tests 1 and 2) on these external preparations for skin of the present invention were carried out. [Examples 1 to 5, Comparative Examples 1 to 5] 95% by weight alcohol phase 95% ethyl alcohol 25.0 Polyoxyethylene (25 mol) hydrogenated castor oil ether 2.0 Antioxidant / preservative proper amount Perfume proper amount 2 mg of) amount aqueous phase glycerin 5.0 sodium qs ion-exchanged water balance hexametaphosphate in this table <method> aqueous phase, after preparation the alcohol phase were solubilized by mixing them.

[0092]

[Table 2]

(2) Whitening Effect Test-1 (Test Method) 280 subjects who were exposed to sunlight in the summer for 4 hours (2 hours a day for 2 days) were exposed to sunlight. Five days after that day, each sample was applied once in the morning and evening for 8 weeks. Divide the panel into 20 groups and 14
The test was performed on each sample of Examples 1 to 5 and Comparative Examples 1 to 5 as a group. (Evaluation method) The lightening effect after use was determined based on the following criteria.

(Judgment Criteria) Significant effect: Pigmentation became almost inconspicuous. Effective: Pigmentation was very light. Somewhat effective: Pigmentation became light. Invalid: No change. (Judgment) ：: 80% or more of the test subjects showed excellent and effective. ：: The proportion of the test subjects showing excellent and effective was 50% or more and less than 80%. Δ: The proportion of the test subjects showing significant effect and effectiveness was 30% or more and less than 50%. ×: Less than 30% of the test subjects showed significant effect and effectiveness.

[0095]

[Table 3]

As is evident from Table 3, the whitening effect after exposure to sunlight is lower in the examples than in the comparative examples, which prevents the deposition of excessive melanin pigment and prevents the skin from turning black. It was recognized that. This indicates that, as described above, the skin external preparation of the present invention is extremely excellent as a whitening agent for directly preventing darkness, spots, and freckles caused by melanin pigmentation.

It is also known that dullness is at least due to the deposition of melanin pigment. Based on the results, the external preparation for skin of the present invention is a very effective anti-dulling agent that can prevent the occurrence of dullness from the viewpoint of melanin deposition. It shows that it is excellent.

(3) Whitening effect test-2 (Test method) Subject 28 suffering from darkness, spots, freckles, etc.
For 0 people, each sample was taken once in the morning and evening for 3 months.
It was applied to the face daily. Divide the panel into 20 groups and 14
As a group, tests were performed on the samples of Examples 1 to 9 and Comparative Examples 1 to 5 described above. (Evaluation method) The lightening effect after three months was determined based on the following criteria.

(Judgment criteria) Significant effect: Pigmentation became almost inconspicuous. Effective: Pigmentation was very light. Somewhat effective: Pigmentation became light. Invalid: No change. (Judgment) ：: 80% or more of the test subjects showed excellent and effective. ：: The proportion of the test subjects showing excellent and effective was 50% or more and less than 80%. Δ: The proportion of the test subjects showing significant effect and effectiveness was 30% or more and less than 50%. ×: Less than 30% of the test subjects showed significant effect and effectiveness.

[0100]

[Table 4]

As is evident from Table 4, black, spots,
It was recognized that the whitening effect against freckles and the like was better in the examples than in the comparative examples. This indicates that the skin external preparation of the present invention is extremely excellent as a whitening agent that directly improves darkness, spots, and freckles as described above. It also shows that the external preparation for skin of the present invention is extremely excellent as a dulling preventive agent which can improve dullness from the viewpoint of melanin deposition.

Next, examples of the formulations of the skin external preparation of the present invention in various dosage forms are shown. The skin external preparations of the present invention in these formulation examples were all evaluated in the whitening effect tests (-1 and 2).
Was obtained. That is, it has been clarified that the skin external preparations of the present invention in the following dosage forms are extremely excellent as the above-mentioned whitening agents or dulling inhibitors.

Example 4 Cream% by Weight Stearic Acid 5.0 Stearyl Alcohol 4.0 Isopropyl Myristate 18.0 4- [3- (Dimethylphenylsilyl) propoxy] phenol 5.0 Glycerin Monostearate 0 Propylene glycol 10.0 Caustic potash 0.2 Sodium bisulfite 0.01 Preservative proper amount Flavor proper amount Ion exchange water residue

<Production method> Propylene glycol and caustic potassium were added to ion-exchanged water, dissolved, heated and maintained at 70 ° C (aqueous phase). Further, other components were mixed, heated and melted, and kept at 70 ° C. (oil phase). Next, the oil phase was gradually added to the aqueous phase, and after the addition was completed, the temperature was maintained for a while to cause a reaction. Thereafter, the mixture was uniformly emulsified with a homomixer and cooled to 30 ° C. while stirring well to obtain a desired cream.

Example 5 Cream Weight% Stearic Acid 6.0 Sorbitan Monostearate 2.0 Polyoxyethylene (20 mol) Sorbitan Monostearate 1.5 Propylene Glycol 10.0 4- [3- ( Dimethylethylsilyl) propoxy] phenol 1.0 Glycerin trioctanoate 10.0 Squalene 5.0 Sodium bisulfite 0.01 Ethylparaben 0.3 Perfume Appropriate amount Ion-exchanged water residue

<Production method> Propylene glycol was added to ion-exchanged water, dissolved, heated and maintained at 70 ° C (aqueous phase). The other components were mixed, melted by heating, and kept at 70 ° C. (oil phase).
The oil phase was added to the aqueous phase, pre-emulsified, uniformly emulsified with a homomixer, and cooled to 30 ° C. with good stirring to obtain the desired cream.

Example 6 Cream% by weight Stearyl alcohol 7.0 Stearic acid 2.0 Hydrogenated lanolin 2.0 Squalane 5.0 2-Octyldodecyl alcohol 6.0 Polyoxyethylene (25 mol) cetyl alcohol ether 3 Glycerin monostearate 2.0 Propylene glycol 5.0 4- [3- (Triphenylsilyl) propoxy] phenol 0.5 Fragrance Appropriate amount Sodium bisulfite 0.03 Ethyl paraben 0.3 Ion exchange water Residue

<Production method> Propylene glycol was added to ion-exchanged water, dissolved, heated and maintained at 70 ° C (aqueous phase). The other components were mixed, melted by heating, and kept at 70 ° C. (oil phase).
The oil phase was added to the water phase to carry out preliminary emulsification, and after uniform emulsification with a homomixer, the mixture was cooled to 30 ° C. while stirring well to obtain a desired cream.

Example 7 Emulsion Weight% Stearic Acid 2.5 Cetyl Alcohol 1.5 Vaseline 5.0 Liquid Paraffin 10.0 Polyoxyethylene (10 mol) Monooleate 2.0 Polyethylene Glycol 1500 3 0.0 Triethanolamine 1.0 4- [3- (Trimethylsilyl) ethoxy] phenol 2.0 Sodium bisulfite 0.01 Ethylparaben 0.3 Carboxyvinyl polymer 0.05 Perfume Appropriate amount Deionized water residue

<Production Method> A carboxyvinyl polymer was dissolved in a small amount of ion-exchanged water (phase A). Next, polyethylene glycol 1500 and triethanolamine were added to the remaining ion-exchanged water, dissolved by heating, and kept at 70 ° C. (aqueous phase). In addition, the other components are mixed and melted by heating to 70 ° C.
(Oil phase). The oil phase was added to the aqueous phase to perform preliminary emulsification, the phase A was added, and the mixture was uniformly emulsified with a homomixer. After the emulsification, the mixture was cooled to 30 ° C. while stirring well to obtain a desired emulsion.

Example 8 Emulsion Weight% (Oil Phase) Stearyl Alcohol 1.5 Squalene 2.0 Vaseline 2.5 Deodorized Liquid Lanolin 1.5 Evening Primrose Oil 2.0 Isopropyl Myristate 5.0 Glycerin Monooleate 2 2.0 Polyoxyethylene (60 mol) hydrogenated castor oil 2.0 Tocopherol acetate 0.05 Ethylparaben 0.2 Butylparaben 0.1 4- [3- (Triethylsilyl) propoxyphenol 0.1 Perfume Appropriate ) Sodium bisulfite 0.01 Glycerin 5.0 Sodium hyaluronate 0.01 Carboxyvinyl polymer 0.2 Potassium hydroxide 0.2 Ion exchange water Residue

<Production method> The oil phase and the aqueous phase were each heated to 70 ° C.
, And the two were mixed, emulsified with an emulsifier, and then cooled to 30 ° C. with a heat exchanger to obtain a desired emulsion.

Example 9 Jelly wt% 95% ethyl alcohol 10.0 dipropylene glycol 15.0 polyoxyethylene (50 mol) oleyl alcohol ether 2.0 carboxyvinyl polymer 1.0 caustic soda 0.15 L-arginine 0.1 4- [3- (Dimethylethylsilyl) propoxy] phenol 3.0 Methylparaben 0.2 Perfume Appropriate amount Deionized water residue

<Production method> The carboxyvinyl polymer was uniformly dissolved in ion-exchanged water, while 4-
[3- (Dimethylethylsilyl) propoxy] phenol was dissolved and added to the aqueous phase. Next, other components were added thereto, then neutralized with caustic soda and L-arginine and thickened to obtain a desired jelly.

[Example 10] Beauty liquid weight% (phase A) 95% ethyl alcohol 10.0 polyoxyethylene (20 mol) octyldodecanol 1.0 methyl paraben 0.15 pantothenyl ethyl ether 0.1 4- [ 3- (Trimethylsilyl) propoxy] phenol 0.1 (B phase) Potassium hydroxide 0.1 (C phase) Glycerin 5.0 Dipropylene glycol 10.0 Sodium bisulfite 0.03 Carboxyvinyl polymer 0.2 Ion exchange water Residue

<Production Method> The phases A and C were uniformly dissolved, and the phase A was added to the phase C to solubilize it. Next, after adding the phase B to this solubilized material, filling was performed to obtain a desired beauty serum.

[Example 11] Pack weight% (phase A) dipropylene glycol 5.0 polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (phase B) 4- [3- (trimethylsilyl) propoxy] phenol 1 0.0 Olive oil 5.0 Tocophenol acetate 0.2 Ethyl paraben 0.2 Perfume 0.2 (Phase C) Sodium bisulfite 0.03 Polyvinyl alcohol (Saponification degree 90, polymerization degree 2000) 13.0 Ethanol 7.0 Ion exchange water residue

<Production Method> A phase, B phase, and C phase were uniformly dissolved, respectively, and first, B phase was added to A phase for solubilization. Next, after adding this solubilized substance to phase C, filling was performed to obtain a desired pack.

Example 12 Ointment% by weight Polyoxyethylene (30 mol) cetyl ether 2.0 Glycerin monostearate 10.0 Liquid paraffin 10.0 Vaseline 40.0 Cetanol 6.0 Methyl paraben 0.1 Butyl paraben 0 .1 Glycerin monostearate 2.0 4- [3- (dimethylethylsilyl) propoxy] phenol 1.0 Propylene glycol 10.0 Ion-exchanged water Residual perfume Appropriate amount

<Production Method> Propylene glycol was added to ion-exchanged water, dissolved, heated and maintained at 70 ° C. (aqueous phase). Then, other components were mixed and dissolved at 70 ° C. (oil phase). The oil phase was added to the aqueous phase, and the mixture was uniformly emulsified with a homomixer, cooled, and filled to obtain a desired ointment.

Example 13 Sunscreen Oil Weight% Decamethylcyclopentasiloxane 46.0 Dimethylpolysiloxane (10 cs / 25 ° C.) 20.0 Methylphenylpolysiloxane (10 cs / 25 ° C.) 18.0 Silicone resin 0 p-Dimethylaminobenzoic acid 2-ethylhexyl ester 3.0 Trimethoxycinnamic acid (bis (trimethylsiloxy) methylsilyl 2.0 isopentyl ester 4- [3- (trimethylsilyl) propoxy] phenol 1.0 Perfume Appropriate amount

<Production method> After mixing and dissolving the above ingredients at 70 ° C, the mixture was cooled and filled to obtain a desired sunscreen oil.

[Example 14] Emulsion (W / O type) wt% (oil phase part) Octamethylcyclotetrasiloxane 10.5 Dimethylpolysiloxane (100cs) 5.0 Dimethylpolysiloxane (2,500,000cs) 3 Liquid paraffin 15.0 polyether-modified silicone 6.0 p-dimethylaminobenzoic acid 2-ethylhexyl ester 5.0 trimethoxycinnamic acid (bis (trimethylsiloxy) methylsilyl 2.0 isopentyl ester 4- [3- (trimethylsilyl) ) Propoxy] phenol 5.0 perfume appropriate amount (aqueous phase) sodium L-glutamate 3.0 1,3-butylene glycol 5.0 preservative 0.2 ion-exchanged water residue

<Production> 1,3-butylene glycol was added to ion-exchanged water, dissolved, heated and maintained at 70 ° C. (aqueous phase). Other components were mixed and dissolved at 70 ° C. (oil phase). The aqueous phase was added to the oil phase, and the mixture was uniformly emulsified with a homomixer, cooled, and filled to obtain a desired emulsion.

Example 15 Emulsion (O / W type) wt% (oil phase) Decamethylcyclopentasiloxane 3.0 Isopropyl myristate 2.0 Vaseline 4.0 Liquid paraffin 8.0 Cetanol 4.0 Stearin Acid 3.0 p-Dimethylaminobenzoic acid 2-ethylhexyl ester 3.0 Trimethoxycinnamic acid (bis (trimethylsiloxy) methylsilyl 1.0 isopentyl ester 4- [3- (trimethylsilyl) propoxy] phenol 1.0 Perfume Appropriate preservative Agent 0.2 (aqueous phase) Glycerin 10.0 Propylene glycol 5.0 Hyaluronic acid 0.01 Potassium hydroxide 0.2 Deionized water Residue

<Production Method> The above-mentioned aqueous phase components were mixed, heated and maintained at 70 ° C. (aqueous phase). Other components were mixed and dissolved at 70 ° C. (oil phase). The oil phase was added to the aqueous phase, and the mixture was uniformly emulsified with a homomixer, cooled, and filled to obtain a desired emulsion.

[Example 16] Lotion% by weight (oil phase part) Dimethylpolysiloxane (5cs) 3.0 Methylphenylpolysiloxane (20cs) 17.0 Liquid paraffin 8.0 Stearic acid 1.0 p-Dimethylaminobenzoate Acid 2-ethylhexyl ester 5.0 trimethoxycinnamic acid (bis (trimethylsiloxy) methylsilyl 1.0 isopentyl ester 4- [3- (triethylsilyl) propoxy] phenol 1.0 fragrance appropriate amount preservative 0.2 (aqueous phase ) Glycerin 10.0 Montmorillonite 0.5 Potassium hydroxide 0.2 Deionized water Residue

<Production Method> The above-mentioned aqueous phase components were mixed and dissolved, and heated and maintained at 70 ° C. (aqueous phase). In addition, other components
To dissolve (oil phase). The oil phase was added to the aqueous phase, and the mixture was uniformly emulsified with a homomixer, cooled, and filled to obtain a desired lotion.

[Example 17] Dual use foundation weight% (part A) Silicone-treated titanium oxide 9.5 Silicone-treated mica 40.0 Silicone-treated talc 20.45 Silicone-treated iron oxide 7.5 Granular nylon powder 10.0 (B Part) p-dimethylaminobenzoic acid 2-ethylhexyl ester 0.1 trimethoxycinnamic acid (bis (trimethylsiloxy) methylsilyl 0.5 isopentyl ester trimethylolpropane triisostearate 5.0 squalane 3.0 beeswax 2.0 Sorbitan triolate 2.0 Vitamin E 0.05 4- [3- (Trimethylsilyl) propoxy] phenol 1.0 Perfume Appropriate amount Preservative 0.2 Glycerin 10.0 Montmorillonite 0.5 Potassium hydroxide 0.2 Ion exchange water Residue

<Production method> [0130] Part A was mixed with a fencial mixer, and a mixture obtained by heating and dissolving part B was added and mixed, followed by pulverization and molding into a middle plate to obtain a desired dual-use foundation. .

[Example 18] Stick cosmetics (% by weight) (part A) Titanium oxide 9.5 Zinc oxide 7.0 Mica 16.0 Red iron oxide 1.5 Yellow iron oxide 1.5 Black iron oxide 1.5 (Part B) Dimethylpolysiloxane (20cs) 29.4 2-Ethylhexyl p-dimethylaminobenzoate 0.1 Trimethoxycinnamic acid (bis (trimethylsiloxy) methylsilyl 0.5 Isopentyl ester Trimethylolpropanetri-2-ethylhexa Noate 8.0 Liquid paraffin 7.0 Sorbitan sesquiolate 1.0 4- [3- (Trimethylsilyl) propoxy] phenol 1.0 Liquid paraffin 7.0 Antioxidant 0.1 (C part) Microcrystalline wax 2. 0 solid paraffin 6.0 ceresin 1.0 perfume appropriate amount

<Production Method> Part A was mixed with a Henschel mixer, and a solution obtained by heating and dissolving Part B was added and mixed, followed by pulverization. Then, the desired stick-shaped cosmetic was obtained by molding.

[Example 19] Makeup base cream weight% (oil phase) Squalane 19.0 Glycerin triisostearate 10.0 Isopar G 5.0 Sorbitan sesquiolate 5.0 2-Ethylhexyl p-dimethylaminobenzoate Ester 5.0 Trimethoxycinnamic acid (bis (trimethylsiloxy) methylsilyl 1.0 isopentyl ester 4- [3- (trimethylsilyl) propoxy] phenol 1.0 Antioxidant Appropriate amount Flavor Appropriate amount Preservative 0.2 (aqueous phase) 1,3-butylene glycol 5.0 Fine particle titanium oxide 10.0 Preservative 0.2 Deionized water residue

<Production Method> The above-mentioned aqueous phase components were mixed and dissolved, and heated to 70 ° C. (aqueous phase). Also, the other components are 70
The mixture was mixed and dissolved at 90 ° C. (oil phase). The above aqueous phase was added to the oil phase, uniformly emulsified with a homomixer, cooled, and filled to obtain a desired cosmetic base cream.

The conventional whitening component is water-soluble or fat-soluble, but even if it is a fat-soluble whitening component, it is hardly soluble in silicone oil which is currently widely used for the purpose of imparting water repellency. Was. That is, the compatibility between the silicone component and the conventional whitening component is poor, and it has been difficult to formulate both of them. On the other hand, the derivative of the present invention is excellent in compatibility with silicone oil, and even if it is a skin external preparation containing a silicone component as described above, the desired skin external preparation can be easily produced by a conventional method. Is possible (for example,
The above Examples 16 to 18 etc.) became clear.

[0136]

Industrial Applicability According to the present invention, it has an excellent melanin production-inhibiting action, for example, is excellent in skin whitening effect for preventing skin pigmentation which occurs after spots, freckles or sunburn, etc., and is stable and safe. The present invention provides a hydroquinone silane derivative which is excellent in compatibility with a base component in a skin external preparation, and a whitening agent and a dulling inhibitor containing the hydroquinone silane derivative as an active ingredient.

[Brief description of the drawings]

FIG. 1 is a drawing showing the results of analysis of monoallyl hydroquinone by gas chromatography.

FIG. 2 is a view showing the results of analysis of monoallylhydroquinone by GC / MS analysis.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Rumiko Fujiwara 1050 Nippa-cho, Kohoku-ku, Yokohama-shi, Kanagawa Inside Shiseido First Research Center Co., Ltd.

Claims (4)

[Claims] 1. A hydroquinone silane derivative represented by the following formula (1): (Wherein, R ¹ represents a divalent linking group containing at least 2 carbon atoms, R ² , R ³ and R ⁴ may be the same or different, and an organic group having 1 or more and 8 or less carbon atoms) X represents a hydrogen atom or a protecting group for a phenolic hydroxyl group). 2. An external preparation for skin containing the hydroquinone silane derivative (I) according to claim 1 as an active ingredient. 3. A whitening agent comprising the hydroquinone silane derivative (I) according to claim 1 as an active ingredient. 4. A dulling inhibitor comprising the hydroquinone silane derivative (I) as an active ingredient.