JPH1129516A - Guaiacol derivative, beautifully whitening agent and skin agent for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide the subject new compound having a more excellent beautifully skin-whitening effect than that of hydroquinone and useful as an ingredient for beautifully whitening agents and stable and highly safe skin agents used for external uses and excellent in the beautifully whitening effect. SOLUTION: A compound of the formula (R is a 1-18C alkyl, a 3-8C cycloalkyl). For example, 1-(3-hydroxy-4-methoxyphenyl)-1-ethanol. The compound of the formula is obtained e.g. by reacting 3-hydroxy-4-methoxybenzaldehyde with a Grignard reagent of an arbitrary alkyl halide having a 1-18C alkyl or 3-8C cycloalkyl group in an ether solvent.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel guaiacol derivative having a skin lightening effect and a salt thereof, and to a skin external use containing these compounds as an active ingredient, which is excellent in skin lightening effect, stable and highly safe. Agent.

[0002]

2. Description of the Related Art Although there are some unclear factors about the mechanism of skin spots, freckles, and pigmentation on skin after sunburn, there are some unknown factors, but in general, hormonal abnormalities and irritation of ultraviolet rays from sunlight cause the problem. It is considered that melanin pigment is formed, and this is abnormally deposited in the skin.

[0003] In order to treat such spots, freckles, pigmentation on the skin after tanning, etc., a substance that suppresses the production of melanin, for example, a method of administering a large amount of vitamin C, or glutathione is injected. In addition, a method of applying kojic acid, cysteine, or the like to an ointment, a cream, a lotion, or the like, and applying the composition locally is used.

[0004] In Europe and the United States, hydroquinone preparations are used as pharmaceuticals. In addition, various other skin external preparations for the purpose of whitening, for example, alkyl catechol glycosides (JP-A-4-59718), tachyside (JP-A-5-310747), curcumin, capsaicin, 4- Hydroxy-3-methoxycinnamaldehyde (JP-A-6-227959), tetraacetylguthayacol β-D-glucoside (JP-A-6-2)
No. 56138) is known.

[0005]

However, these compounds, except for hydroquinone, exhibit very slow effects, so that the whitening effect is not sufficient. On the other hand, although the effects of hydroquinone have been recognized, However, this also has a problem in the safety (irritation and sensitization) of the substance itself, so that its use is generally restricted.

In view of the above circumstances, the present inventors have conducted intensive studies on a substance having a whitening effect, and as a result, it has been found that a novel guaiacol derivative having a specific structure and a salt thereof exhibit a whitening effect more than hydroquinone. They discovered that they had safety and completed the present invention.

An object of the present invention is to provide a novel guaiacol derivative and a salt thereof, a novel whitening agent containing the novel guaiacol derivative and / or a salt thereof as an active ingredient, and an external preparation for skin containing the same.

[0008]

That is, the present invention provides a guaiacol derivative represented by the following general formula (1) and a salt thereof.

Embedded image (In the formula, R represents a linear or branched alkyl group having 1 to 18 carbon atoms or a cycloalkyl group having 3 to 8 carbon atoms.)

The present invention also provides a whitening agent comprising the above guaiacol derivative and / or a salt thereof.

[0010] The present invention further provides a skin external preparation characterized by containing the guaiacol derivative and / or a salt thereof.

Further, the present invention provides the above external preparation for skin, wherein the amount of the guaiacol derivative and / or salt thereof is 0.001 to 20.0% by weight based on the total amount of the external preparation for skin. To provide.

[0012]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The configuration of the present invention will be described below in detail.

The guaiacol derivative and its salt according to the present invention are novel compounds and can be synthesized, for example, by the following method. That is, 3-hydroxy-4-methoxybenzaldehyde, which can be easily obtained as a commercial product, is converted into a linear or branched alkyl group having 1 to 18 carbon atoms or an arbitrary cycloalkyl group having 3 to 8 carbon atoms. It can be produced by performing a Grignard reaction in an ether solvent using a Grignard reagent of an alkyl halide.

The compound of the present invention produced as described above may be, if desired, an inorganic salt such as a sodium salt, a potassium salt, an ammonium salt, a magnesium salt or a calcium salt, or monoethanolamine, diethanolamine, triethanolamine, or the like. Organic salts such as dicyclohexylamine can be used.

Specifically, the substance names of the novel compound of the present invention are exemplified by 1- (3-hydroxy-4-methoxyphenyl) -1-ethanol, 1- (3-hydroxy-4-
Methoxyphenyl) -1-propanol, 1- (3-hydroxy-4-methoxyphenyl) -1-butanol,
1- (3-hydroxy-4-methoxyphenyl) -1-
Pentanol, 1- (3-hydroxy-4-methoxyphenyl) -1-hexanol, 1- (3-hydroxy-
4-methoxyphenyl) -1-heptanol, 1- (3
-Hydroxy-4-methoxyphenyl) -1-octanol, 1- (3-hydroxy-4-methoxyphenyl)
-1-nonanol, 1- (3-hydroxy-4-methoxyphenyl) -1-decanol, 1- (3-hydroxy-4-methoxyphenyl) -1-undecanol, 1-
(3-hydroxy-4-methoxyphenyl) -1-dodecanol, 1- (3-hydroxy-4-methoxyphenyl) -1-tetradecanol, 1- (3-hydroxy-
4-methoxyphenyl) -1-hexadecanol, 1-
(3-hydroxy-4-methoxyphenyl) -1-octadecanol, 1- (3-hydroxy-4-methoxyphenyl) -2-methyl-1-propanol, 1- (3-
(Hydroxy-4-methoxyphenyl) -2-methyl-1
-Butanol, 1- (3-hydroxy-4-methoxyphenyl) -3-methyl-1-butanol, 1- (3-hydroxy-4-methoxyphenyl) -2,2-dimethyl-1-propanol and the like. .

The above compound of the present invention has a skin whitening effect, and can provide a whitening agent containing the compound of the present invention substantially as an active ingredient and a skin external preparation containing the compound of the present invention.
The skin external preparation of the present invention contains at least one or more of the above guaiacol derivatives and / or salts thereof, and the compounding amount is 0.001 to 20.0% by weight based on the total amount of the skin external preparation.
Preferably it is 0.01 to 10.0% by weight, particularly preferably 0.1 to 7.0% by weight. If it is less than 0.001% by weight, the skin whitening effect is poor, and even if it exceeds 20.0% by weight, no increase in the effect can be expected.

The external preparation for skin of the present invention can be prepared into various forms by a conventional method, respectively. In general, cream, ointment, gel, lotion, emulsion, stick, pack, It is preferable to use a solution with an organic solvent.

The external preparation for skin of the present invention contains, in addition to the above-mentioned essential components, other components usually used in external preparations for skin such as cosmetics and pharmaceuticals, for example, powder components, liquid oils, solid oils, waxes, Hydrocarbons, higher fatty acids, higher alcohols,
Esters, silicone, anionic surfactant, cationic surfactant, amphoteric surfactant, nonionic surfactant,
Moisturizers, water-soluble polymer compounds, thickeners, coating agents, ultraviolet absorbers, sequestering agents, lower alcohols, polyhydric alcohols, sugars, amino acids, organic amines, synthetic resin emulsions, pH adjusters, skin Nutrients, vitamins, antioxidants, antioxidants, fragrances, water, etc. can be added as needed. Specific examples of components that can be blended are listed below. The external preparation for skin of the present invention can be produced by a conventional method by blending any one or more of these components with the above essential components.

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, fluoroapatite, hydroxyapatite, ceramic powder, metal soap (zinc myristate, calcium palmitate, aluminum stearate), inorganic powder such as boron nitride, 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, cellulo Organic powders scan powder such as titanium dioxide, inorganic white pigments such as zinc oxide, iron oxide (red iron oxide),
Inorganic red pigments such as iron titanate, inorganic brown pigments such as γ-iron oxide, yellow iron oxide, inorganic yellow pigments such as loess black iron oxide, carbon black, inorganic black pigments such as lower 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 ultramarine blue and dark blue; titanium oxide coated mica; titanium oxide coated bismuth oxychloride , Titanium oxide coated talc, colored titanium oxide coated mica, bismuth oxychloride, pearl pigments such as fish scale foil, aluminum powder,
Metal powder pigments such as copper powder, Red No. 201, Red No. 202, Red No. 204, Red No. 205, Red 220
No. Red 226, Red 228, Red 405, Orange 203, Orange 204, Yellow 205, Yellow 401
No. 3, and organic pigments such as Blue No. 404, Red No. 3, Red No. 104, Red No. 106, Red No. 227, Red No. 230
No. Red No. 401, Red No. 505, Orange No. 205, Yellow No. 4, Yellow No. 5, Yellow No. 202, Yellow No. 203, Green No. 3
Organic pigments such as zirconium, barium or aluminum lakes such as No. 1 and Blue No. 1, and natural pigments such as chlorophyll and β-carotene. However, the powder may be any powder that can be applied to general cosmetics, and is not limited to the above components.

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 mentioned.

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, mocro kernel oil, hardened kernel oil Oil, beef tallow, mocro, hardened castor oil and the like.

Examples of waxes include beeswax, candelilla wax, cotton wax, carnauba wax, bayberry wax, ibota wax, whale wax, montan wax, nuka wax, lanolin, kapok wax, lanolin acetate, liquid lanolin,
Sugar cane wax, isopropyl lanolin fatty acid, 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

Examples of the hydrocarbon oil include liquid paraffin, ozokerite, squalene, pristane, paraffin, ceresin, squalene, petrolatum, microcrystalline wax and the like.

The higher fatty acids include, for example, lauric acid, myristic acid, palmitic acid, stearic acid, behenic (behenic) acid, oleic acid, 12-hydroxystearic acid, undecylenic acid, tallic acid, isostearic acid, linoleic acid, linoleic acid Acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and the like.

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), and 2-decyltetradecyl. And branched-chain alcohols such as knol, lanolin alcohol, cholesterol, phytosterol, hexyldecanol, isostearyl alcohol, octyldodecanol, and the like.

Examples of synthetic ester oils include isopropyl myristate, cetyl octoate, octyl dodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, hexyl decyl dimethyl octanoate, Cetyl lactate, myristyl lactate, lanolin acetate, isocetyl stearate, isocetyl isostearate, cholesteryl 12-hydroxystearate, ethylene glycol di-2-ethylhexylate, fatty acid ester of dipentaerythritol, N-alkyl glycol monoisostearate, neodicaprate Pentyl glycol, diisostearyl malate, glycerin di-2-heptylundecanoate, trimethylol tri-2-ethylhexylate Bread, trimethylolpropane triisostearate, pentaneerythritol tetra-2-ethylhexylate, glycerin tri-2-ethylhexylate, trimethylolpropane triisostearate, cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, trimyristate Glycerin, 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.

Examples of the silicone include linear polysiloxanes such as dimethylpolysiloxane, methylphenylpolysiloxane and methylhydrogenpolysiloxane, and cyclic polysiloxanes such as decamethylpolysiloxane, dodecamethylpolysiloxane and tetramethyltetrahydrogenpolysiloxane. Examples include polysiloxane, silicone resin and silicone rubber forming a three-dimensional network structure.

Examples of the anionic surfactant include soap base, fatty acid soaps such as sodium laurate and sodium palmitate, higher alkyl sulfates such as sodium lauryl sulfate and lauryl sulfate K,
POE lauryl sulfate triethanolamine, alkyl ether sulfates such as POE lauryl sodium sulfate, N-acyl sarcosine acids such as lauroyl sarcosine sodium, N-myristoyl-N-methyltaurine sodium, coconut oil fatty acid methyltauride sodium,
Higher fatty acid amide sulfonates such as sodium lauryl methyl tauride, POE oleyl ether sodium phosphate, phosphate ester salts such as POE stearyl ether phosphoric acid, sodium di-2-ethylhexyl sulfosuccinate, monolauroyl monoethanolamide polyoxyethylene Sulfosuccinates such as sodium sulfosuccinate and sodium lauryl polypropylene glycol sulfosuccinate; alkylbenzene sulfonates such as sodium linear dodecylbenzenesulfonate, linear dodecylbenzenesulfonate triethanolamine and linear dodecylbenzenesulfonate; monosodium N-lauroylglutamate , N-stearoyl disodium glutamate, N-myristoyl-L-monosodium glutamate and the like. Acyl glutamate, higher fatty acid ester sulfate such as hydrogenated coconut oil fatty acid glycerin sodium sulfate, sulfated oil such as funnel oil, POE alkyl ether carboxylic acid, POE alkyl allyl ether carboxylate, α-olefin sulfonate, higher grade Fatty acid ester sulfonate, secondary alcohol sulfate, higher fatty acid alkylolamide sulfate,
Sodium lauroyl monoethanolamidosuccinate,
N-palmitoyl aspartate ditriethanolamine, sodium caseinate and the like.

Examples of the cationic surfactant include alkyltrimethylammonium salts such as stearyltrimethylammonium chloride and lauryltrimethylammonium chloride; distearyldimethylammonium dialkyldimethylammonium chloride; Alkylpyridinium salts such as 5-methylenepiperidinium) and cetylpyridinium chloride, alkyl quaternary ammonium salts, alkyldimethylbenzylammonium salts, alkylisoquinolinium salts, dialkylmorphonium salts, POE alkylamines, alkylamine salts, Examples thereof include polyamine fatty acid derivatives, amyl alcohol fatty acid derivatives, benzalkonium chloride, benzethonium chloride and the like.

Examples of the amphoteric surfactant include 2-undecyl-N, N, N- (hydroxyethylcarboxymethyl) -2-imidazoline sodium and 2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyl. Imidazoline amphoteric surfactants such as roxy disodium salt, 2-heptadecyl-N-carboxymethyl-
N-hydroxyethyl imidazolinium betaine, lauryl dimethylamino acetate betaine, alkyl betaine,
Betaine-based surfactants such as amidobetaine and sulfobetaine are exemplified.

Examples of the lipophilic nonionic surfactant include sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, Sorbitan fatty acid esters such as penta-2-ethylhexyl diglycerol sorbitan, tetra-2-ethylhexyl diglycerol sorbitan, mono-cottonseed oil fatty acid glycerin, glycerin monoerucate, glycerin sesquioleate, glyceryl monostearate, α,
Glycerin polyglycerin fatty acids such as glycerin α'-oleate pyroglutamate and glyceryl monostearate; propylene glycol fatty acid esters such as propylene glycol monostearate; hydrogenated castor oil derivatives; glycerin alkyl ether;

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-sorbitan. Sorbit Monolaurate, POE-Sorbit Monooleate, POE
-POE sorbitol fatty acid esters such as sorbit pentaoleate and POE-sorbit monostearate, POE glycerin fatty acid esters such as POE-glycerin monostearate, POE-glycerin monoisostearate and POE-glycerin triisostearate; POE monooleate, POE distearate,
POE fatty acid esters such as POE monodioleate and ethylene glycol cysteate, POE lauryl ether, POE oleyl ether, POE stearyl ether, POE behenyl ether, POE alkyl ethers such as 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 type such as bruronic;
POE / POP alkyl ethers such as POP cetyl ether, POE / POP2-decyltetradecyl ether, POE / POP monobutyl ether, POE / POP hydrogenated lanolin, POE / POP glycerin ether, and tetraPOE / tetraPOP ethylenediamine such as Tetronic Condensates, POE castor oil, POE hardened castor oil, POE hardened castor oil monoisostearate, P
OE hardened castor oil triisostearate, POE hardened castor oil monopyroglutamic acid monoisostearate diester, POE hardened castor oil, maleic acid, etc. POE castor oil hardened castor oil derivative, POE sorbitol bee wax, etc. POE beeswax lanolin derivative, coconut oil Alkanolamides such as fatty acid diethanolamide, lauric acid monoethanolamide, fatty acid isopropanolamide,
POE propylene glycol fatty acid ester, POE alkylamine, POE fatty acid amide, sucrose fatty acid ester, POE nonylphenylformaldehyde condensate,
Examples thereof include alkylethoxydimethylamine oxide and trioleyl phosphoric acid.

Examples of humectants include polyethylene glycol, propylene glycol, glycerin, 1,3
-Butylene glycol, xylitol, sorbitol,
Maltitol, chondroitin sulfate, hyaluronic acid, mucoitin sulfate, caronic acid, atelocollagen, cholesteryl-12-hydroxystearate, sodium lactate, bile salts, dl-pyrrolidone carboxylate, short-chain soluble collagen, diglycerin (EO) PO Examples include an adduct, a primrose extract, a Yarrow extract, and a melilot extract.

Examples of natural water-soluble polymers include, for example, gum arabic, tragacanth, galactan, guar gum, carob gum, karaya gum, carrageenan, pectin, agar, quince seed (quince), alge colloid (cassow extract), starch (rice, corn) , Potato, wheat), plant polymers such as glycyrrhizic acid, microbial polymers such as xanthan gum, dextran, succinoglucan, pullulan, collagen,
Animal-based polymers such as casein, albumin, and gelatin are exemplified.

As the semi-synthetic water-soluble polymer, for example,
Starch-based polymers such as carboxymethyl starch and methylhydroxypropyl starch, methylcellulose, nitrocellulose, ethylcellulose, methylhydroxypropylcellulose, hydroxyethylcellulose, cellulose sodium sulfate, hydroxypropylcellulose, sodium carboxymethylcellulose (CM
C), cellulosic polymers such as crystalline cellulose and cellulose powder, and alginic acid polymers such as sodium alginate and propylene glycol alginate.

Examples of the synthetic water-soluble polymer include vinyl polymers such as polyvinyl alcohol, polyvinyl methyl ether, polyvinylpyrrolidone and carboxyvinyl polymer (Carbopol), polyethylene glycol 20,000, 4,000,000, and the like. Polyoxyethylene polymer such as 600,000, polyoxyethylene polyoxypropylene copolymer copolymer polymer, acrylic polymer such as sodium polyacrylate, polyethyl acrylate, polyacrylamide, polyethyleneimine, cationic polymer And the like.

Examples of the inorganic water-soluble polymer include bentonite, A1Mg silicic acid (Vegum), laponite, hectorite, silicic anhydride and the like.

As the thickener, for example, gum arabic,
Carrageenan, karaya gum, tragacanth gum, carob gum, quince seed (quince), casein, dextrin, gelatin, sodium pectate, sodium alginate, methylcellulose, ethylcellulose,
CMC, hydroxyethylcellulose, hydroxypropylcellulose, PVA, PVM, PVP, sodium polyacrylate, carboxyvinyl polymer, locust bean gum, guar gum, tamarind gum, dialkyldimethylammonium cellulose sulfate, xanthan gum, aluminum magnesium silicate, bentonite,
Hectorite and the like.

As the ultraviolet absorber, for example, para-aminobenzoic 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
Benzoic acid ultraviolet absorbers such as -dimethyl PABA butyl ester and N, N-dimethyl PABA tyl ester; anthranilic acid ultraviolet absorbers such as homomenthyl-N-acetylanthranilate; amyl salicylate; menthyl salicylate; homomenthyl salicylate; octyl Salicylic acid type ultraviolet absorbers such as salicylate, phenyl salicylate, benzyl salicylate, p-isopropanol phenyl salicylate, octyl cinnamate,
Ethyl-4-isopropylcinnamate, methyl-2,
5-diisopropylcinnamate, ethyl-2,4-diisopropylcinnamate, methyl-2,4-diisopropylcinnamate, 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-cyano-β-phenylcinnamate, Cinnamic acid ultraviolet absorbers such as 2-ethylhexyl-α-cyano-β-phenylcinnamate, glyceryl mono-2-ethylhexanoyl-diparamethoxycinnamate, 2,4-dihydroxybenzophenone, 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,
-Ethylhexyl-4'-phenyl-benzophenone-
Benzophenone-based ultraviolet absorbers such as 2-carboxylate, 2-hydroxy-4-n-octoxybenzophenone, and 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'-t-octylphenyl) benzotriazole, 2- (2'-hydroxy-5'-methylphenylbenzotriazole, dibenzarazine, dianisoylmethane, 4-methoxy -4'-t-butyldibenzoylmethane, 5- (3,3-dimethyl-2-norbornylidene) -3-pentan-2-one, etc. These ultraviolet absorbers and various plants having an ultraviolet absorption action By adding various ultraviolet-absorbing substances such as extracts, a skin external preparation having both a preventive effect and a therapeutic effect on sunburn can be obtained.

As the sequestering agent, for example, 1-
Hydroxyethane-1,1-diphosphonic acid, 1-hydroxyethane-1,1-diphosphonic acid tetrasodium salt, disodium edetate, trisodium edetate, tetrasodium edetate, sodium citrate, sodium polyphosphate, metaphosphoric acid Examples include sodium, gluconic acid, phosphoric acid, citric acid, ascorbic acid, succinic acid, edetic acid and the like.

As the lower alcohol, for example, methanol, ethanol, propanol, isopropanol,
Isobutyl alcohol, t-butyl alcohol and the like.

Examples of the polyhydric alcohol include ethylene glycol, propylene glycol, trimethylene glycol, 1,2-butylene glycol, 1,3-butylene glycol, tetramethylene glycol, and 2,3-butylene glycol.
Butylene glycol, pentamethylene glycol, 2-
Dihydric alcohols such as butene-1,4-diol, hexylene glycol and octylene glycol; trihydric alcohols such as glycerin, trimethylolpropane and 1,2,6-hexanetriol; and tetrahydric alcohols such as pentaerythritol Pentahydric alcohols such as xylitol, sorbitol, hexahydric alcohols such as mannitol,
Polyhydric alcohol polymers such as diethylene glycol, dipropylene glycol, triethylene glycol, polypropylene glycol, tetraethylene glycol, diglycerin, polyethylene glycol, triglycerin, tetraglycerin, polyglycerin, ethylene glycol monomethyl ether, ethylene glycol monoethyl Ether, ethylene glycol monobutyl ether, ethylene glycol monophenyl ether, ethylene glycol monohexyl ether, ethylene glycol mono 2-methylhexyl ether, ethylene glycol isoamyl ether, ethylene glycol benzyl ether, ethylene glycol isopropyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl Ether, d Dihydric alcohol alkyl ethers such as lenglycol dibutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, diethylene glycol butyl ether, diethylene glycol methyl ethyl ether, triethylene glycol monomethyl ether, triethylene Glycol monoethyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monobutyl ether, propylene glycol isopropyl ether, dipropylene glycol methyl ether, dipropylene glycol ethyl ether Dihydric alcohol alkyl ethers such as dipropylene glycol butyl ether, ethylene glycol monomethyl ether acetate, ethylene glycol monoethyl ether acetate, ethylene glycol monobutyl ether acetate, ethylene glycol monophenyl ether acetate, ethylene glycol diadibate, ethylene glycol disuccinate Dihydric alcohol ethers such as diethylene glycol monoethyl ether acetate, diethylene glycol monobutyl ether acetate, propylene glycol monomethyl ether acetate, propylene glycol monoethyl ether acetate, propylene glycol monopropyl ether acetate, propylene glycol monophenyl ether acetate, etc. Glycerin monoalkyl ethers such as ter, xyl alcohol, serachyl alcohol, and batyl alcohol, sorbitol, maltitol, maltotriose, mannitol, sucrose, erythritol, glucose, fructose, starch-degrading sugar, maltose, xylitolose,
Sugar alcohols such as starch-decomposed sugar-reducing alcohol, glysolid, tetrahydrofurfuryl alcohol, PO
E Tetrahydrofurfuryl alcohol, POP butyl ether, POP / POE butyl ether, tripolyoxypropylene glycerin ether, POP glycerin ether, POP glycerin ether phosphoric acid, POP
POE pentane erythritol ether and the like.

Examples of the monosaccharide include tricarbonates such as D-glyceryl aldehyde and dihydroxyacetone, tetracarbons such as D-erythrose, D-erythrulose, D-threose and erythritol, L-arabinose, D-xylose, and the like. Pentoses such as L-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, D-tagatose, heptose such as aldoheptose and heppulose;
Octanose such as octulose, 2-deoxy-D-ribose, 6-deoxy-L-galactose, 6-deoxy-
Deoxy sugars such as L-mannose, D-glucosamine, D
-Amino sugars such as galactosamine, sialic acid, aminouronic acid and muramic acid, and uronic acids such as D-glucuronic acid, D-mannuronic acid, L-guluronic acid, D-galacturonic acid and L-iduronic acid.

Examples of the oligosaccharide include sucrose, guntianose, umbelliferose, lactose, planteose, isorikunoses, α, α-trehalose,
Raffinose, liqunoses, umbilicin, stachyose bell bath courses and the like.

Polysaccharides include, for example, 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. As amino acids, for example, glycine, alanine, valine, leucine, isoleucine, serine, threonine,
Tryptophan, cystine, cysteine, methionine,
Examples include neutral amino acids such as proline and hydroxyproline, acidic amino acids such as aspartic acid, glutamic acid, asparagine and glutamine, and basic amino acids such as arginine, histidine, lysine and hydroxylysine. Examples of amino acid derivatives include acyl sarcosine sodium (sodium lauroyl sarcosine), acyl glutamate, sodium acyl β-alanine, glutathione, and pyrrolidone carboxylic acid.

As the organic amine, for example, monoethanolamine, diethanolamine, triethanolamine, morpholine, triisopropanolamine, 2-amino-2-methyl-1,3-propanediol, 2-amino-2-methyl-1 -Propanol and the like.

As the synthetic resin emulsion, for example,
An acrylic resin emulsion, a polyethyl acrylate emulsion, an acrylic resin liquid, a polyacryl alkyl ester emulsion, a polyvinyl acetate resin emulsion, and the like are included.

Examples of the pH adjusting agent include buffers such as lactic acid-sodium lactate and citric acid-sodium citrate.

Examples of the vitamins include vitamins A, B1, B2, B6, E and derivatives thereof, pantothenic acid and derivatives thereof, and biotin.

Examples of the antioxidant include tocopherols, dibutylhydroxytoluene, butylhydroxyanisole, gallic esters and the like.

As the antioxidant aid, for example, phosphoric acid,
Examples thereof include citric acid, ascorbic acid, maleic acid, malonic acid, succinic acid, fumaric acid, kephalin, hexametaphosphate, phytic acid, and ethylenediaminetetraacetic acid.

The dosage form of the external preparation for skin of the present invention is optional.
With one or more of the above optional components, such as a solution system, a solubilizing system, an emulsifying system, an oil-liquid system, a gel system, a powder dispersion system, a water-oil two-layer system, a water-oil-powder three-layer system, etc. By blending the essential components of the present invention, a wide range of dosage forms can be obtained according to the desired product by a conventional method.

The external preparation for skin of the present invention refers to those applied to the outer skin (including the scalp) as cosmetics, pharmaceuticals, and quasi-drugs, and can be used for any purpose. , Creams, packs, and other facial cosmetics, foundations, makeup cosmetics such as lipsticks, eye shadows and the like, body cosmetics, aromatic cosmetics, scalp hair cosmetics, cleaning agents, ointments, and the like.

[0054]

Next, the present invention will be described in more detail by way of examples. The present invention is not limited by this.

First, a synthesis example of the guaiacol derivative and a salt thereof according to the present invention will be described in detail.

"Synthesis Example 1: 1- (3-hydroxy-4-
Synthesis of methoxyphenyl) -1-ethanol "Methylmagnesium bromide (3.0 M ether solution, 30 ml, 90 ml
A solution of 3-hydroxy-4-methoxybenzaldehyde (4.62 g, 30 mmole) in anhydrous tetrahydrofuran (50 ml) was added dropwise to the resulting solution under stirring at room temperature with a dropping funnel.
After stirring at room temperature for 3 hours, ether (200 ml) was added to the reaction system.
) And 1N-sulfuric acid (90 ml, 9 ml
0 mmole) was added dropwise with a dropping funnel. The reaction solution was transferred to a separatory funnel, and the ether layer was collected.
The residue was washed with an aqueous solution of sodium hydrogen sulfite to remove residual aldehyde, further washed with an aqueous solution of saturated sodium hydrogen carbonate and water, and dried over sodium sulfate. The ether layer was concentrated under reduced pressure, and the residue was crystallized from hexane to obtain 1- (3-hydroxy-4-methoxyphenyl) -1-ethanol as white crystals. The yield was 1.96 g (38% yield). ¹ H-NMR (400 MHz, CDCl ₃ , TMS, ppm) δ 1.45 (d, 3H, J = 6.4 Hz, CH ₃ ) δ 1.81 (bs, 1H, OH) δ 3.87 (S, 3H, OCH ₃ ) δ 4.79 (q, 1H, J = 6.4 Hz, CH) δ 5.68 (bs, 1H, phenol) δ 6.81 (d, 1H, J = 8.3 Hz, benzene ring H-5) δ 6.85 (dd, 1H, J = 2.0) 8.3 Hz, benzene ring H-6) δ 6.94 (d, 1H, J = 2.0 Hz, benzene ring H-2) ¹³ C-NMR (100 MHz, CDCl ₃ , TMS, ppm) δ 25.0 (CH ₃ ), δ 56.1 (OCH ₃ ), δ 70.1
(CH), δ 110.8, δ 112.0, δ 117.0, δ 139.4,
δ 145.8, δ 146.0 (benzene ring)

"Synthesis Example 2: 1- (3-hydroxy-4-
Synthesis of methoxyphenyl) -1-butanol "n-propylmagnesium bromide (2.0 M ether solution, 26 m
l, 52 mmole), a solution of 3-hydroxy-4-methoxybenzaldehyde (3.14 g, 20 mmole) in anhydrous tetrahydrofuran (40 ml) was added dropwise with stirring at room temperature with a dropping funnel. After stirring at room temperature for 3 hours, ether (1
00N), and 1N-sulfuric acid (52 m
l, 52 mmole) was added dropwise through a dropping funnel. The reaction solution was transferred to a separating funnel, and the ether layer was collected.
The remaining aldehyde was removed by washing with a 10% aqueous sodium hydrogen sulfite solution, and a saturated aqueous sodium hydrogen carbonate solution was further added.
After washing sequentially with water, it was dried with sodium sulfate. The ether layer was concentrated under reduced pressure, and the residue was separated and purified using a silica gel column (developing solvent: toluene: ethyl acetate = 2: 1 [V / V]).
1- (3-hydroxy-4-methoxyphenyl) -1-
Butanol was obtained as a colorless transparent oil. Yield 2.92 g
(74% yield). ¹ H-NMR (400 MHz, CDCl ₃ , TMS, ppm) δ 0.91 (t, 3H, J = 7.3 Hz, CH ₃ ) δ 1.20 to 1.50 (m, 2H, CH ₂ ) δ 1.58 to 1.90 (m, 3H) , CH ₂ , OH) δ 3.87 (S, 3H, OCH ₃ ) δ 4.56 (bdd, 1H, J = 6.4,6.8 Hz, CH) δ 5.67 (s, 1H, phenol) δ 6.81 (s, 2H, benzene ring ) Δ 6.92 (s, 1H, benzene ring) ¹³ C-NMR (100 MHz, CDCl ₃ , TMS, ppm) δ 13.9 (CH ₃ ), δ 19.1 (CH ₂ ), δ 41.1
(CH ₂ ), δ 56.1 (OCH ₃ ), δ 74.1 (C
H), δ 110.7, δ 112.4, δ 117.6, δ 138.5, δ 1
45.8, δ 146.0 (benzene ring)

Next, examples of whitening agents and skin external preparations will be described in detail. All amounts are by weight.

“Examples 1 to 6, Comparative Examples 1 to 6: External preparation for skin” Alcohol phase 95% ethyl alcohol 25.0% by weight Polyoxyethylene (25 mol) hydrogenated castor oil ether 2.0 Antioxidant / preservative Agent Suitable amount Perfume Suitable amount Whitening agent (Table 1) Amount shown in Table 1 Aqueous phase Glycerin 5.0 Sodium hexametaphosphate Appropriate amount Deionized water Residue (Preparation method) After preparing the aqueous phase and alcohol phase, solubilize.

[0060]

[Table 1] ---------------------------------------------- -------------------------- Whitening agent (compound name) Compounding amount ---------------- -------------------------------------------------- ----- Example 1 1- (3-hydroxy-4-methoxyphenyl) -1-ethanol 1.0 ----------------------- ------------------------------------------------ Example 21- (3-hydroxy-4-methoxyphenyl) -1-ethanol 0.01 ------------------------------ ----------------------------------------- Example 3 1- (3-hydroxy -4-methoxyphenyl) -1-ethanol 10.0 ------------------------------------- ---------------------------------- Example 4 1- (3-hydroxy-4-methoxyphenyl)- 1-butanol 1.0 -------------------------------------------- --------------------------- Example 5 1- (3-hydroxy-4-methoxyphenyl) -1-butanol 0.01- -------------------------------------------------- -------------------- Example 6 1- (3-hydroxy-4-methoxyphenyl) -1-butanol 10.0 ---------------------------- ------------------------------------------- Comparative Example 1 No blending- -------------------------------------------------- ------------------- Comparative Example 2 Hydroquinone 1.0 -------------------------- --------------------------------------------- Comparative Example 3 Curcumin 1.0 -------------------------------------------------- --------------------- Comparative Example 4 Tetraacetylguaiacol-β-D-glucoside 1.0 ---------------- -------------------------------------------------- ----- Comparative Example 5 Takioside 1.0 ---------------------------------------- ------------------------------- Comparative Example 6 4-t-butyl-2-β-D-glucopyranosyl Catechol 1.0 ---------------------------------------------- -------------------------

"(1) Whitening effect test 1" (Test method) The subject was exposed to sunlight in the upper arm of 120 subjects who were exposed to sunlight in summer for 4 hours (2 hours a day for 2 days). Each sample was applied once a day in the morning and evening for 5 weeks after 5 days on the day. Divide the panel into 10 groups and 12 groups
The test was performed on each sample of Examples 1 to 6 and Comparative Examples 1 to 6 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.

[0063]

[Table 2] ---------------------------------------------- -------------------- Working example Comparative example -------------------------- ---------------------------------------- 1 2 3 4 5 6 1 2 3 4 5 6 ------------------------------------------------ ------------------ Whitening effect: ◎ ○ ◎ ◎ ○ ◎ × △ △ △ △ △ ----------------- -------------------------------------------------

As is clear from Table 2, the whitening effect after exposure to sunlight was less in the example than in the comparative example, which prevented the deposition of excess melanin pigment and prevented the skin from turning black. This indicates that the compound of the present invention has an excellent whitening effect.

"(2) Whitening effect test 2" (Test method) Subject 12 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 10 groups and 12 groups
The test was performed on each sample of Examples 1 to 6 and Comparative Examples 1 to 6 as a group.

(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.

[0067]

[Table 3] ---------------------------------------------- -------------------- Working example Comparative example -------------------------- ---------------------------------------- 1 2 3 4 5 6 1 2 3 4 5 6 ------------------------------------------------ ------------------ Whitening effect ◎ ○ ◎ ◎ ○ ◎ × △ △ △ △ △ ------------------ ------------------------------------------------

As is clear from Table 3, the whitening effect on the black and white, spots, freckles and the like was found to be superior in the examples as compared with the comparative examples, and the compounds of the present invention showed excellent whitening. It can be seen that it has an effect.

Hereinafter, other examples of the whitening agent and the skin external preparation of the present invention will be described.

Example 7: Cream Stearic Acid 5.0% by Weight Stearyl Alcohol 4.0 Isopropyl Myristate 18.0 Glycerin Monostearate 3.0 Propylene Glycol 10.0 1- (3-hydroxy-4- Methoxyphenyl) -1-ethanol 20.0 caustic potash 0.2 sodium bisulfite 0.01 preservatives qs perfume qs Ion exchange water residue (production method) Add propylene glycol and caustic potash to ion exchange water, heat and dissolve. Keep at ° C (aqueous phase). The other components are mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase is gradually added to the water phase, and after the addition is completed, the temperature is maintained for a while to cause a reaction. Thereafter, the mixture was uniformly emulsified with a homomixer, cooled to 30 ° C. with good stirring, and manufactured.

Example 8: Cream Stearic acid 6.0% by weight Sorbitan monostearate 2.0 Polyoxyethylene (20 mol) Sorbitan monostearate 1.5 Propylene glycol 10.0 1- (3- (Hydroxy-4-methoxyphenyl) -1-butanol 7.0 Glycerin trioctanoate 10.0 Squalene 5.0 Sodium bisulfite 0.01 Ethyl paraben 0.3 Perfume Appropriate amount Ion exchange water Residue (Preparation method) Ion exchange Propylene glycol is added to water, dissolved and heated to 70 ° C. (aqueous phase). The other components are mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase was added to the aqueous phase, pre-emulsified, homogenized with a homomixer, and cooled to 30 ° C. while stirring well to produce.

Example 9: Cream Stearyl alcohol 7.0% by weight Stearic acid 2.0 Hydrogenated lanolin 2.0 Squalane 5.0 2-octyldodecyl alcohol 6.0 Polyoxyethylene (25 mol) cetyl alcohol ether 3.0 Glycerin monostearate 2.0 Propylene glycol 5.0 1- (3-Hydroxy-4-methoxyphenyl) -1-propanol 0.001 Fragrance Appropriate amount Sodium bisulfite 0.03 Ethylparaben 0.3 Ion-exchanged water residue (Preparation method) Add propylene glycol to ion-exchanged water, dissolve and heat to 70 ° C (aqueous phase). The other components are mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase was added to the water phase, pre-emulsified, homogenized uniformly with a homomixer, and cooled to 30 ° C. with good stirring to produce.

Example 10: Emulsion 2.5% by weight of stearic acid Cetyl alcohol 1.5 Vaseline 5.0 Liquid paraffin 10.0 Polyoxyethylene (10 mol) monooleate 2.0 Polyethylene glycol 1500 3.0 Triethanolamine 1.0 1- (3-Hydroxy-4-methoxyphenyl) -1-ethanol 10.0 Sodium bisulfite 0.01 Ethylparaben 0.3 Carboxyvinyl polymer 0.05 Fragrance Appropriate ion Exchange water residue (Preparation method) Dissolve the carboxyvinyl polymer in a small amount of ion exchange water (phase A). Polyethylene glycol 1500 and triethanolamine are added to the remaining ion-exchanged water, dissolved by heating, and maintained at 70 ° C. (aqueous phase). The other components are mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase was added to the water phase, preliminarily emulsified, the phase A was added, and the mixture was uniformly emulsified with a homomixer.

Example 11: Emulsion (oil phase) Stearyl alcohol 1.5% by weight squalene 2.0 Vaseline 2.5 Deodorized liquid lanolin 1.5 Evening primrose oil 2.0 Isopropyl myristate 5.0 Glycerin monooleate 2.0 Polyoxyethylene (60 mol) hydrogenated castor oil 2.0 Tocopherol acetate 0.05 Ethyl paraben 0.2 Butyl paraben 0.1 1- (3-Hydroxy-4-methoxyphenyl) -1-ethanol 1 1.0 1- (3-hydroxy-4-methoxyphenyl) -1-butanol 1.0 Perfume Appropriate amount (aqueous phase) Sodium bisulfite 0.01% by weight Glycerin 5.0 Sodium hyaluronate 0.01 Carboxyvinyl Polymer 0.2 Potassium hydroxide 0.2 Purified water Residue (Preparation method) Dissolve the oil phase at 70 ° C 70 ° C in the aqueous phase
, And the oil phase was mixed with the aqueous phase, emulsified by an emulsifier, and then cooled to 30 ° C. by a heat exchanger to produce.

Example 12: Jelly 95% ethyl alcohol 10.0% by weight dipropylene glycol 15.0 polyoxyethylene (50 mol) oleyl alcohol ether 2.0 carboxyvinyl polymer 1.0 caustic soda 0.15 L- Arginine 0.1 1- (3-hydroxy-4-methoxyphenyl) -1-ethanol 1.0 1- (3-hydroxy-4-methoxyphenyl) -1-butanol 1.0 methylparaben 0.2 Perfume Appropriate amount Ion-exchange water Residue (Preparation method) A carboxyvinyl polymer is uniformly dissolved in ion-exchange water, while 1- (3-hydroxy-4-methoxyphenyl) -1-ethanol, 95% ethanol is used.
-(3-Hydroxy-4-methoxyphenyl) -1-butanol, polyoxyethylene (50 mol) oleyl alcohol ether are dissolved and added to the aqueous phase. Next, after adding other components, the mixture was neutralized with caustic soda and L-arginine to increase the viscosity, and thus produced.

“Example 13: Beauty liquid” (Phase A) Ethanol (95%) 10.0% by weight Polyoxyethylene (20 mol) octyldodecanol 1.0 Methyl paraben 0.15 Pantothenyl ethyl ether 0.1 1 -(3-hydroxy-4-methoxyphenyl) -1-propanol 0.05 (B phase) Potassium hydroxide 0.1 (C phase) Glycerin 5.0 Dipropylene glycol 10.0 Sodium bisulfite 0.03 Carboxyvinyl polymer 0.2 Purified water residue (Preparation method) Dissolve A phase and C phase uniformly, and add A to C phase
Add phases and solubilize. Next, after the phase B was added, the mixture was filled and produced.

Example 14: Pack (Phase A) Dipropylene glycol 5.0% by weight Polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (Phase B) 1- (3-hydroxy-4-methoxyphenyl) ) -1-Ethanol 1.0 1- (3-hydroxy-4-methoxyphenyl) -1-butanol 1.0 Olive oil 5.0 Tocophenol acetate 0.2 Ethylparaben 0.2 Fragrance 0.2 (Phase C) Sodium bisulfite 0.03 Polyvinyl alcohol (degree of saponification 90, degree of polymerization 2000) 13.0 Ethanol 7.0 Purified water Residue (Preparation method) A phase, B phase, and C phase are uniformly dissolved, respectively. A
Add phase B to phase and solubilize. Subsequently, this was added to the phase C and then filled to produce.

Example 15 Ointment Polyoxyethylene (30 mol) cetyl ether 2.0% by weight 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 1- (3-Hydroxy-4-methoxyphenyl) -1-ethanol 5.0 Propylene glycol 10.0 Ion-exchanged water Residual perfume Appropriate amount (production method) To ion-exchanged water Add propylene glycol,
Dissolve and heat to maintain 70 ° C. (aqueous phase). 70 other ingredients
Mix and dissolve at ℃ (oil phase). The oil phase was added to the aqueous phase, uniformly emulsified by a homomixer, cooled, and filled to produce a product.

The skin external preparations obtained in Examples 7 to 15 were all effective in the same whitening effect test as in Examples 1 to 6.

[0080]

According to the present invention, a novel guaiacol derivative and a salt thereof having an excellent skin whitening effect, a whitening agent containing the novel compound of the present invention as an active ingredient, and a stable composition containing the novel compound of the present invention. And a highly safe skin external preparation having an excellent whitening effect.

Claims (4)

[Claims] 1. A guaiacol derivative represented by the following general formula (1) and a salt thereof. Embedded image (In the formula, R represents a linear or branched alkyl group having 1 to 18 carbon atoms or a cycloalkyl group having 3 to 8 carbon atoms.) 2. A whitening agent comprising the guaiacol derivative according to claim 1 and / or a salt thereof as an active ingredient. 3. An external preparation for skin, comprising the guaiacol derivative according to claim 1 and / or a salt thereof. 4. The amount of the guaiacol derivative and / or salt thereof is 0.001 to 2 with respect to the total amount of the external preparation for skin.
The skin external preparation according to claim 3, wherein the amount is 0.0% by weight.