JPH07173024A - Skin external preparation - Google Patents

Abstract

PURPOSE:To obtain a skin external preparation enhanced in whitening effect of an alkoxysalicyclic acid (salt) which is a whitening active ingredient and having excellent whitening effect and high safety. CONSTITUTION:This skin external preparation contains one or two or more kinds of placenta extract and an alkoxysalicylic acid of the formula (R is an alkoxy) and/or its salt. The compound of the formula is preferably blended in an amount of 0.001-20wt.%, especially 0.01-10wt.% and the placenta extract is preferably blended in an amount of 0.001-5wt.%, especially 0.01-3wt.% based on total amount of the skin external preparation. As the placenta extract, dried powder, a carbonized material, a hydrolyzate or a heat extract of an animal placenta or a human placenta, or an animal placenta extract or a human placenta extract, etc., is used. When the skin external preparation is further blended with acidic mucopoly-saccharides, vitamin E esters, p-oxybenzoic acid esters or an alkylenediamine carboxylic acid derivative, its whitening effect is enhanced.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an external preparation for skin, and more particularly to improvement of a whitening active ingredient.

[0002]

2. Description of the Related Art There are various types of skin pigment abnormalities from cosmetic ones such as spots and freckles to those found in skin diseases such as liver spots and freckles. Although there are many unclear points about the mechanism of action of these pigment abnormalities, in general, melanin pigments are formed due to hormonal abnormalities and ultraviolet rays from sunlight, etc., which are abnormally deposited in the skin. It is believed that. Melanin production inhibitors have been used as symptomatic treatments for the treatment of such pigmentary abnormalities. For example, a method of orally administering a large amount of vitamin C, a method of injecting glutathione or the like, or kojic acid, vitamin C and its A method of locally applying a derivative, cysteine or the like in the form of an ointment, cream, lotion or the like is used. However, the fact is that these methods have not yet been sufficiently effective. On the other hand, in Europe and America, hydroquinone, which is a melanin production inhibitor, is used as a drug for the purpose of depigmenting pigment spots.

[0003]

However, the effect of hydroquinone is extremely slow, and its whitening effect is not sufficient. Although hydroquinone itself has a whitening effect, its use is restricted because of its safety problem. Derivatives that reduce the side effects of this hydroquinone and are excellent in the whitening effect have been investigated, but those having both sufficient effect and safety have not been obtained yet. The present invention has been made in view of the above technical problems, and an object thereof is to provide a skin external preparation having an excellent whitening effect and high safety.

[0004]

As a result of intensive studies to solve the above-mentioned problems of the prior art, the present inventors have found that certain alkoxysalicylic acid has a melanin production-inhibiting action and, together with a placenta extract, It is found that the whitening effect when applied to the skin is significantly improved by using it,
The present invention has been completed.

That is, the external preparation for skin according to claim 1 of the present invention contains a placenta extract and one or more kinds of alkoxysalicylic acid and / or a salt thereof represented by the following general formula (A). It is characterized by General formula (A):

[Chemical 2] (In the formula, R represents an alkoxy group.) The external skin preparation according to claim 2 of the present invention is characterized in that, in the general formula (A), the alkoxy group is a methoxy group. The external preparation for skin according to claim 3 of the present invention is characterized in that, in the general formula (A), the alkoxy group is an ethoxy group. The external preparation for skin according to claim 4 of the present invention is characterized by further containing one or more acidic mucopolysaccharides. The external preparation for skin according to claim 5 of the present invention is characterized by further containing one or more vitamin E esters. The external skin preparation according to claim 6 of the present invention is characterized by further containing one or more paraoxybenzoic acid esters. The external preparation for skin according to claim 7 of the present invention is characterized by further containing an alkylenediamine carboxylic derivative.

The structure of the present invention will be described in detail below. Alkoxysalicylic acid used in the external preparation for skin of the present invention is a known substance, for example, 5-methoxysalicylic acid is Be.
il, 10,227,4-methoxysalicylic acid is Bei
It can be easily synthesized by the method described in No. 1, 10379. Further, it is commercially available as a reagent from Aldrich (Germany) or the like, and it is also possible to use this.

The alkoxysalicylic acid used in the present invention is a salicylic acid in which the hydrogen atom at the 3-position, 4-position or 5-position is substituted with an alkoxy group,
The alkoxy group which is a substituent is preferably a methoxy group,
It is any one of an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group and an isobutoxy group, more preferably a methoxy group or an ethoxy group. A specific example of the compound name is 3-hydroxysalicylic acid (2-hydroxy-3-methoxybenzoic acid).
acid) 3-Ethoxysalicylic acid (2-hydroxy-3-ethoxybenzoic
acid) 4-methoxy-4-methoxybenzoic acid
acid) 4-ethoxy-4-ethoxybenzoic acid
acid) 4-propoxysalicylic acid (2-hydroxy-4-propoxybenzo
ic acid) 4-isopropoxysalicylic acid (2-hydroxy-4-isopropo
xybenzoic acid) 2-butoxysalicylic acid
acid) 5-methoxysalicylic acid
acid) 5-ethoxy-5-ethoxybenzoic acid
acid) 5-propoxysalicylic acid (2-hydroxy-5-propoxybenzo
ic acid) and the like.

The above-mentioned alkoxysalicylic acid can be made into a salt by a known method, but the external preparation for skin of the present invention may contain alkoxysalicylic acid in the form of a salt. Such salts are not particularly limited, for example,
In addition to alkali metal salts or alkaline earth metal salts such as sodium salts, potassium salts and calcium salts, ammonium salts, amino acid salts and the like salts can be mentioned. Although the above-mentioned alkoxysalicylic acid or its salt is an existing substance, its whitening effect is not known at all, and it has been clarified for the first time by the present inventors.It was once incorporated into a skin external preparation for the purpose of whitening. There is no example.

In order to obtain an effective whitening effect in the external preparation for skin of the present invention, the content of alkoxysalicylic acid and / or its salt is preferably 0.001 to 20% by weight based on the total amount of the external preparation for skin. Preferably 0.
It is from 01 to 10% by weight. If the blending amount is less than 0.001% by weight, the whitening effect is poor, and if the blending amount exceeds 20% by weight, the whitening effect reaches a peak and the effect corresponding to the increase in the blending amount cannot be expected to increase. Furthermore, the present inventors have found that the placenta extract is extremely effective for enhancing the whitening effect of the alkoxysalicylic acid and / or its salt. The placenta extract used in the present invention is a dry powder of animal placenta or human placenta,
Examples thereof include a charcoal-based material, a hydrolyzate and a warm extract, an animal placenta extract and a placenta extract.

The extraction method of the extract as referred to herein is not particularly limited, but it will be described by way of example. For example, bovine placenta is thoroughly washed with water, finely crushed, and bleeding well. Purified water is added to this to homogenize at low temperature. And an extract obtained by continuously extracting. Examples of commercially available products include placenta liquid (KURT RICHTER-Shou Chemical), which is an animal placenta extract, and placenta V (Ichimaru Boeki), which is a human placenta extract, and Placenta AF (Sansho Pharmaceutical).

In the present invention, one or more of the above placenta extracts are used. The amount of the placenta extract used in the present invention is 0.001 in the external preparation for skin.
To 5% by weight, more preferably 0.01 to 3% by weight
Is. If it is less than 0.001% by weight, a sufficient effect of promoting percutaneous absorption may not be observed, and if it exceeds 5% by weight, no further effect may be expected.
By the way, the present inventors, while advancing research on the above-mentioned external preparation for skin, provided acidic mucopolysaccharides, vitamin E esters, paraoxybenzoic acid esters, alkylenediaminecarboxylic acid derivatives with the alkoxysalicylic acid or salts thereof of the present invention and It has been found that when added to a skin external preparation containing a placenta extract, its whitening effect is enhanced. These are known to have their effects as moisturizers, blood flow promoters, antiseptics, and bactericides, and are incorporated into cosmetics, etc., but their whitening effect enhancing action has not been known until now. .

The acidic mucopolysaccharides used in the present invention to further enhance the whitening effect include, for example:
Sodium hyaluronate, sodium chondroitin sulfate and the like can be mentioned, and the blending amount thereof is preferably 0.01 to 10% by weight, more preferably 0.0
It is 1 to 3% by weight. In addition, vitamin E used in the present invention
Examples of the esters include α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol,
Examples thereof include tocopherol acetate, tocopherol nicotinate, and the like, and examples of the paraoxybenzoic acid include methylparaben, ethylparaben, butylparaben, and the like. As the alkylenediaminecarboxylic acid derivative, ethylenediaminetetraacetic acid or a salt thereof is preferable. Examples of the alkylenediaminecarboxylate include alkali metal salts such as sodium salt, potassium salt, magnesium salt and the like, alkaline earth metal salts, ammonium salt, alkanol salt and the like, and sodium salt is preferable.

The amount of these vitamin E esters and / or paraoxybenzoic acid esters and / or alkylenediaminecarboxylic acid derivatives blended is preferably 0.01 to 3% by weight, and more preferably 0, relative to the skin external preparation. 0.05 to 0.3% by weight. The dosage form of the external preparation for skin of the present invention can be arbitrarily selected as long as its effect can be sufficiently exerted, and for example, a lotion, a solubilizing system such as a liquid agent,
In addition to emulsion systems such as emulsions and creams and dispersion systems such as makeup cosmetics, packs, jellies, ointments and the like can be mentioned. In addition to the above-mentioned essential components, the external preparation for skin of the present invention includes components that are usually used in external preparations for skin such as cosmetics and pharmaceuticals, for example, other whitening agents, moisturizers, antioxidants, and other oily components. , UV absorber, surfactant, moisturizer, thickener,
Alcohols, powder components, coloring materials, aqueous components, water, various skin nutrients and the like can be appropriately blended as necessary.

Examples of the oily component include camellia oil, macadamia nut oil, olive oil, castor oil, safflower oil, soybean oil, tea seed oil, cacao butter, coconut oil, hardened coconut oil,
Palm oil, Mokurou, hydrogenated castor oil, beeswax, candelilla wax, carnauba wax, lanolin, liquid lanolin,
Jojoba wax, hard lanolin, natural oils and fats such as polyoxyethylene lanolin alcohol ether, polyoxyethylene cholesterol ether, liquid paraffin, ozokerite, squalene, paraffin, ceresin, petrolatum, hydrocarbon oils such as microcrystalline wax, myristic acid Isopropyl, octyldodecyl myristate, isopropyl palmitate, cholesteryl 12-hydroxystearate, ethylene glycol di-2-ethylhexylate, dipentaerythritol fatty acid ester, tetra-2-ethylhexyl pentaerythritol, tri-2-ethylhexyl glycerin,
Synthetic oil components such as trimethylolpropane triisostearate, cetyl-2-ethylhexanoate, castor oil fatty acid methyl ester, chain polysiloxanes such as dimethylpolysiloxane, methylphenylpolysiloxane, methylhydrogenpolysiloxane, decamethyl Examples thereof include cyclic polysiloxanes such as polysiloxane, dodecamethylpolysiloxane, and tetramethyltetrahydrogenpolysiloxane, silicone resins capable of forming a three-dimensional network structure, and silicones such as silicone rubber.

Examples of the ultraviolet absorber include benzoic acid type ultraviolet rays such as paraaminobenzoic acid, paraaminobenzoic acid monoglycerin ester, N, N-dipropoxyparaaminobenzoic acid ethyl ester and N, N-dimethylparaaminobenzoic acid ethyl ester. Absorbent, homomenthyl-N
Anthranilic acid type ultraviolet absorber such as acetylanthranilate, amyl salicylate, homomenthyl salicylate, octyl salicylate, phenyl salicylate,
Salicylic acid UV absorbers such as benzyl salicylate and p-isopropanol phenyl salicylate, octyl cinnamate, ethyl-4-isopropyl cinnamate, methyl-2,5-diisopropyl cinnamate, ethyl-2,4-diisopropyl cinnamate, propyl- p-methoxycinnamate, isoamyl-p-methoxycinnamate, octyl-p-methoxycinnamate (2-ethylhexyl-p-methoxycinnamate),
2-ethoxyethyl-p-methoxycinnamate, 2-
Ethylhexyl-α-cyano-β-phenylcinnamate, glyceryl mono-2-ethylhexanoyl-di-p
-Cinnamic acid-based UV absorbers such as methoxycinnamate,
2,4-dihydroxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, 2,2 ',
4,4′-tetrahydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonate, 4
-Phenylbenzophenone, 2-ethylhexyl-4 '
Benzophenone-based UV absorbers such as phenylbenzophenone-2-carboxylate, 3- (4'-methylbenzylidene) -d, l-camphor, 3-benzylidene-d, l-camphor, urocanic acid, urocanic acid ethyl ester, 2,2'-hydroxy-5-methylphenylbenzotriazole, 2- (2'-hydroxy-
5'-t-octylphenyl) benzotriazole, dibenzalazine, dianisoylmethane, 4-methoxy-
4'-t-butyldibenzoylmethane, 5- (3,3-
Dimethyl-2-norbornylidene) -3-pentane-2
-ON and the like.

Examples of lipophilic nonionic surfactants include sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate and penta-2. Sorbitan fatty acid esters such as diglycerol sorbitan ethylhexylate, glyceryl monostearate, glycerin α, α'-oleic acid pyroglutamate, glycerin monostearate glycerin or esters of polyglycerin such as malate ester, propylene monostearate Propylene glycol fatty acid esters such as glycol, hydrogenated castor oil derivative, glycerin alkyl ether and the like can be mentioned.

Examples of hydrophilic nonionic surfactants include polyoxyethylene sorbitan monooleate,
Polyoxyethylene sorbitan monostearate and other polyoxyethylene sorbitan fatty acid esters, polyoxyethylene sorbit monolaurate, polyoxyethylene sorbit monooleate, polyoxyethylene sorbit monostearate and other polyoxyethylene sorbit fatty acid esters, Polyoxyethylene glycerin monostearate, polyoxyethylene glycerin monoisostearate, polyoxyethylene glycerin triisostearate, etc., polyoxyethylene glycerin fatty acid ester, polyoxyethylene monooleate, polyoxyethylene distearate, etc. Polyoxyethylene fatty acid esters, polyoxyethylene lauryl ether, polyoxyethylene oleyl ether,
Polyoxyethylene stearyl ether, polyoxyethylene-2-octyldodecyl ether, polyoxyethylene cholestanol ether, and other polyoxyethylene alkyl ethers, polyoxyethylene octylphenyl ether, polyoxyethylene nonylphenyl ether, polyoxyethylene dinonyl Phenyl ether,
Polyoxyethylene alkyl phenyl ethers such as
Pluronic type surfactants such as Pluronic, polyoxyethylene polyoxypropylene cetyl ether, polyoxyethylene polyoxypropylene-2-decyl tetradecyl ether, polyoxyethylene polyoxypropylene monobutyl ether, polyoxyethylene polyoxypropylene, hydrogenation Lanolin, polyoxyethylene polyoxypropylene glycerin ether and other polyoxyethylene polyoxypropylene alkyl ethers, Tetronic and other tetrapolyoxyethylene / tetrapolyoxypropylene ethylenediamine condensates, polyoxyethylene castor oil, polyoxyethylene curing Castor oil, polyoxyethylene hydrogenated castor oil monoisostearate, polyoxyethylene hydrogenated castor oil triisostearate, polyoxy Styrene hydrogenated castor oil mono-pyroglutamic acid monoisostearate diester, polyoxyethylene castor oil derivative or a polyoxyethylene hydrogenated castor oil derivatives such as polyoxyethylene hydrogenated castor oil maleic acid ester, coconut oil fatty acid diethanolamide,
Lauric acid monoethanolamide, alkanolamides such as fatty acid isopropanolamide, polyoxyethylene propylene glycol fatty acid esters, polyoxyethylene alkylamines, polyoxyethylene fatty acid amide, sucrose fatty acid ester, polyoxyethylene nonylphenyl formaldehyde condensate, Alkyl ethoxy dimethyl amine oxide, trioleyl phosphoric acid, etc. are mentioned.

As the anionic surfactant, for example,
Fatty acid soaps such as sodium laurate and sodium palmitate, higher alkyl sulfate ester salts such as sodium lauryl sulfate and potassium lauryl sulfate, polyoxyethylene lauryl sulfate triethanolamine, alkyl ether sulfate salts such as polyoxyethylene sodium lauryl sulfate, N-acyl sarcosinic acid such as sodium lauroyl sarcosine, N-myristoyl-N-methyl taurine sodium, coconut oil fatty acid methyl tauride sodium, higher fatty acid amide sulfonate such as sodium lauryl methyl tauride, polyoxyethylene oleyl ether phosphate Sodium, phosphate ester salts such as sodium polyoxyethylene stearyl ether phosphate, sodium di-2-ethylhexyl sulfosuccinate, monolauroyl Monoethanolamide sodium polyoxyethylene sulfosuccinate, sulfosuccinates such as sodium lauryl polypropylene glycol sulfosuccinate, sodium linear dodecylbenzenesulfonate, alkylbenzenesulfonates such as triethanolamine linear dodecylbenzenesulfonate, N-lauroylglutamate mono Sodium, N-acyl glutamic acid such as disodium N-stearoyl glutamate, higher fatty acid ester sulfate ester salt such as hydrogenated coconut oil fatty acid glycerin sulfate sodium salt, polyoxyethylene alkyl ether carboxylate salt, α-olefin sulfonate salt, higher fatty acid ester Sulfonate, secondary alcohol sulfate ester salt, higher fatty acid alkylolamide sulfate ester salt, lauroyl monoethano Sodium Amidokohaku acid, N- palmitoyl aspartate, ditriethanolamine, coconut oil fatty acid collagen hydrolyzate alkali salts.

Examples of the cationic surfactant include alkyl trimethyl ammonium salts such as stearyl trimethyl ammonium chloride and lauryl trimethyl ammonium chloride, dialkyl dimethyl ammonium salts such as distearyl dimethyl ammonium chloride, and poly (N, N ').
-Dimethyl-3,5, -methylenepiperidinium), an alkylpyridinium salt such as cetylpyridinium chloride, an alkyl quaternary ammonium salt, an alkyldimethylbenzylammonium salt, an alkylisoquinolinium salt, a dialkylmorphonium salt, polyoxy Ethylene alkyl amine, alkyl amine salt, polyamine fatty acid derivative, amyl alcohol fatty acid derivative, benzalkonium chloride, benzethonium chloride, cationic polymer, acrylic acid β-
Examples thereof include NN-dimethyl-N-ethylammonioethyl vinylpyrrolidone chloride copolymer.

Examples of the amphoteric surfactant include 2-undecyl-N, N, N,-(hydroxyethylcarboxymethyl) -2-imidazoline sodium and 2-cocoyl-2-imidazolinium hydroxide-1-carboxy. Imidazoline-based amphoteric surfactants such as ethyloxy disodium salt, betaine-based such as 2-heptadecyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine, lauryldimethylaminoacetic acid betaine, alkyl betaine, amidobetaine, sulfobetaine Examples include amphoteric surfactants.

Examples of moisturizers include cholesteryl-
12-hydroxystearate, sodium lactate, dl
-Pyrrolidone carboxylate, urea, diglycerin ethylene oxide / propylene oxide adduct, and the like, and particularly when an acidic mucopolysaccharide such as chondroitin sulfate or hyaluronic acid is added, a whitening effect of alkoxysalicylic acid and / or a salt thereof. Has a potentiating effect on.

Examples of the thickener include gum arabic,
Carrageenan, tragacanth gum, quince seed (quince), casein, sodium caseinate, dextrin, gelatin, sodium alginate, methylcellulose, ethylcellulose, carboxymethylcellulose,
Examples thereof include hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer, guar gum, xanthan gum, magnesium aluminum silicate, bentonite, and hectorite.

Examples of the polyhydric alcohol include ethylene glycol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, glycerin,
Examples thereof include erythritol, trimethylolpropane, pentaerythritol, sorbitol, maltitol, diglycerin and polyethylene glycol. Examples of higher alcohols include lauryl alcohol, stearyl alcohol, behenyl alcohol, myristyl alcohol, oleyl alcohol, cetostearyl alcohol, monostearyl glycerin ether (batyl alcohol), lanolin alcohol, cholesterol, phytosterols, isostearyl alcohol, octyldodecanol and the like. Can be mentioned.

Examples of powder components include talc, kaolin, mica, sericite, phlogopite, synthetic mica, magnesium carbonate, calcium carbonate, aluminum silicate, silica, zeolite, barium sulfate, and calcined calcium sulfate ( Burnt gypsum), calcium phosphate, fluoroapatite, hydroxyapatite, ceramic powder, metal soap (zinc myristate, calcium palmitate, aluminum stearate, etc.), inorganic powder such as boron nitride, polyamide resin powder (nylon powder), polyethylene powder, Polymethylmethacrylate powder, polystyrene powder, copolymer resin powder of styrene and acrylic acid,
Polymethicylsesquioxane powder, organic powder such as cellulose powder, titanium dioxide, zinc oxide, iron oxide (red iron oxide), iron titanate, yellow iron oxide, black iron oxide, carbon black, low order titanium oxide, mango violet, Inorganic pigments such as cobalt violet, chromium oxide, ultramarine blue, navy blue,
Titanium oxide coated mica, titanium oxide coated bismuth oxychloride, colored titanium oxide coated mica, bismuth oxychloride, pearl pigments such as fish scale, metal powder pigments such as aluminum powder, red 201,
Red No. 202, Orange No. 203, Yellow No. 205, Yellow 40
Organic pigments such as No. 1, Blue No. 404, Red No. 3, Yellow 4
No. 3, Green No. 3, Blue No. 1, etc. zirconium, barium,
Organic pigments such as aluminum lake, chlorophyll, β-
Examples include natural pigments such as carotene. Examples of synthetic resin emulsions include acrylic resin emulsions,
Examples thereof include polyvinyl acetate resin emulsion.

As amino acids, glycine, leucine,
Examples thereof include phenylalanine, tyrosine, aspartic acid, glutamic acid, sodium glutamate, arginine, histidine, lysine, cystine, cysteine, sodium acylsarcosine (sodium lauroylsarcosine), acylglutamate, glutathione, and pyrrolidonecarboxylic acid.

Examples of the organic amine include monoethanolamine, diethanolamine, triethanolamine, morpholine, triisopropanolamine, 2-amino-2-methyl-1,3-propanediol, 2-amino-2-methyl-1. -Propanol and the like.

Besides, sequestering agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, caffeine, tannin, verapamil, tranexamic acid and its derivatives, licorice extraction Substance, glabridin, hot water extract of fruits of fire thorns, various crude drugs, tocopherol acetate,
Drugs such as glycyrrhizic acid and its derivatives or salts thereof, vitamin C, magnesium ascorbate phosphate,
Other whitening agents such as ascorbic acid glucoside, arbutin, kojic acid, glucose, fructose, mannose,
Sugars such as sucrose and trehalose can be appropriately added, and particularly when vitamin E esters such as tocopherol acetate are added, alkoxysalicylic acid and / or a salt thereof has a whitening effect enhancing effect.

[0028]

[Preparation of reagents]

1) L-DOPA solution 10 mg of L-DOPA (special grade reagent) was dissolved in 20 ml of the phosphate buffer solution of 3) at the time of use to prepare a 0.05% L-DOPA solution. 2) Tyrosinase solution Mushroom tyrosinase (50,000 units / 1
1.7 mg protein, manufactured by SIGMA) 11.7
Dissolve mg in 25 ml of distilled water, 2000 units / m
1 solution. 3) 0.1M phosphate buffer The pH was adjusted to 6.8 by a conventional method. [Preparation of Sample Solution] Each sample shown in Table 1 was diluted with ethanol to 3 levels of concentration to prepare a sample solution. [Test method] The activity of tyrosinase was measured by Pomeran.
tz method was slightly modified to use L-DOP as a substrate.
A (special grade of reagent) was used to measure the absorbance at 475 nm based on the reaction product dopachrome.

That is, 1.0 ml of the L-DOPA solution and 1.8 ml of the phosphate buffer were taken, and 0.1 ml of the sample solution was added thereto.
ml was added. Then 0.1 ml of tyrosinase solution
The mixture was added and mixed and reacted at room temperature for 1.5 minutes. Spectrophotometer (Spectrophotometer manufactured by Hitachi Ltd.)
220A type), the absorbance at 475 nm was measured, and the value was designated as T. As a reagent blank, L-
1.0 ml of distilled water was used in place of the DOPA solution, 1.8 ml of phosphate buffer solution and 0.1 ml of sample solution were added to and mixed with it, and the same operation was followed to measure the absorbance. And

The control is L-DOPA solution 1.0.
Instead of the sample solution, 0.1 ml of ethanol was added to ml and 1.8 ml of phosphate buffer, and the value was designated as C in the same manner. Control reagent blank is L-DOP
1.0 ml of distilled water was used instead of the solution A, and 1.8 ml of phosphate buffer and 0.1 ml of ethanol were added to this.
In the same manner, the value is set as C '. The tyrosinase activity inhibition rate at each sample concentration was calculated by the following formula, and the horizontal axis of the semilogarithmic graph shows the sample concentration (logarithm) and the vertical axis shows the activity inhibition rate. From this graph, the tyrosinase activity 50% inhibition concentration (ID 50) I asked. In addition, T, T ', C, C'was measured 3 times and the average value of each was used.

## EQU1 ## Inhibition rate of tyrosinase activity (%) = 100 × [1
-(TT ') / (CC')]

(2) Whitening effect test [Preparation of samples] Using each sample, a cream was prepared according to the following formulation. The preparation method was in accordance with a conventional method. That is, A
The ingredients are heated to 70 ° C. to dissolve. After the B component is heated and dissolved at 70 ° C., the A component is added thereto and emulsified. Then, heat exchange was performed to obtain a cream. A. Cetanol 4.0 wt% Vaseline 5.0 Liquid paraffin 8.0 Squalane 5.0 Isopropyl myristate 3.0 POE (25) Cetyl ether 2.0 Placental extract (0.5) Preservative Suitable amount B. Whitening agent 0.3 Glycerin 5.0 Propylene glycol 5.0 Purified water Remainder [Test method] One group of 10 subjects was exposed to sunlight in summer for 4 hours (2 hours per day for 2 days). From 5 days after the day of exposure to light, each cream was applied to the skin of the inner part of the upper arm once a morning and evening for 2 weeks. After the application, it was examined whether or not there was an inhibitory effect on the pigmentation induced by UV irradiation, and the degree thereof was evaluated based on the following criteria. ⊚: Eight or more panelists (80% or more) were markedly effective or effective
Above: 5: 5 to 7 panelists (50%) who are markedly effective or effective
Or more and less than 70%) Δ: 3 to 4 panelists (30%) who are markedly effective or effective
Or more and less than 50%) x: 2 or less panelists who are markedly effective or effective (30%
Less than)

Examples 1 to 4 and Comparative Examples a to d (Thiroshi
Nase activity inhibitory action and whitening effect) First, in order to alkoxysalicylic acid of the present invention inhibit the activity of essential tyrosinase melanogenesis, to make sure that actually have a whitening effect on human skin, Table 1
Using the sample shown in (1), a tyrosinase activity inhibition test and a whitening effect test using a human body panel were performed. As a result, as is clear from Table 1, all of the alkoxysalicylic acid of the present invention have a tyrosinase inhibitory action, and particularly 4-
It was confirmed that methoxysalicylic acid and 5-methoxysalicylic acid inhibit the activity even at extremely low concentrations of 1.0 mM and 4.5 mM, respectively.

On the other hand, in the whitening effect test, in all the creams of Examples 1 to 4, 80% or more of the panelists said that the effect was markedly effective or effective, and any of Comparative Examples a to e. The whitening effect was clearly superior to that of the above cream. Then, the comparative example e in which the placenta extract was not added by the addition of only 4-methoxysalicylic acid had a higher whitening effect than the case of using other whitening agents, but the whitening effect was insufficient as compared with the coexisting system of both. Met. Further, with ascorbic acid of Comparative Example c, the tyrosinase activity inhibitory action was extremely high, but since it was water-soluble, it was difficult to be absorbed into the skin, and the whitening effect on the human body panel tended to be rather low.

Further, the hydroquinone of Comparative Example a or the gentisic acid of Comparative Example b is known to have side effects, which is a safety problem. On the other hand, Examples 1 to 1
Alkoxysalicylic acid of No. 4 showed very high safety in any of the groups, with no skin abnormalities such as erythema, eczema and swelling and no side effects such as pain and itch. Although data are omitted, the coexistence system of the alkoxysalicylic acid and / or its salt and the placenta extract of the present invention other than those used in this Example also showed similar tyrosinase activity inhibitory action and excellent whitening effect. , Safety was very high. For example, in the cream containing potassium 4-methoxysalicylate and the placenta extract, 80% or more of the panelists were markedly effective or effective in the whitening effect test.

From the above, the external preparation for skin of the present invention prevents the deposition of melanin pigment by the tyrosinase activity inhibitory action and exerts a remarkable whitening effect, and the whitening effect is enhanced by coexistence with the placenta extract. it is conceivable that.

[Table 1] ───────────────────────────────── Sample ID 50 (mM) Whitening effect Safety ── ─────────────────────────────── Example 1 3-Methoxysalicylic acid 21.0 ◎ ○ Example 2 4-Methoxysalicylic acid 1.0 ◎ ○ Example 3 5-methoxysalicylic acid 4.5 ◎ ○ Example 4 4-ethoxysalicylic acid 2.0 ◎ ○ ───────────────────────────── Comparative Example a Hydroquinone 4.2 △ × Comparative Example b Genticic Acid 13.6 △ △ Comparative Example c Ascorbic acid 0.3 △ ○ Comparative Example d Whitening agent-free − × − Comparative Example e Placental extract 1.0 ○ ○ (As a whitening agent 4-methoxysalicylic acid) ───────────────────────────────────

Examples 5 to 13 and Comparative Example e (whitening effect
(Enhancement action) Next, the enhancement action of various additives on the whitening effect of the alkoxysalicylic acid and / or its salt of the present invention was examined. First, a whitening effect test was conducted using 4-methoxysalicylic acid as the alkoxysalicylic acid and sodium hyaluronate as the acidic mucopolysaccharide. The test cream, in the prescription of the whitening effect test cream,
4-methoxysalicylic acid was added as a sample to the aqueous phase in an amount of 0.3% by weight, a placenta extract of 0.5% by weight, and sodium hyaluronate so as to have the concentrations shown in Table 2, and the sample was prepared for use in the test.

As a result, as is clear from Table 2, 4-
When 0.01% or more of sodium hyaluronate was added to 0.3% of methoxysalicylic acid, the whitening effect was obviously improved as compared with the case of no addition. However, when sodium hyaluronate is added in an amount of 10% or more, the lotion becomes sticky and the sensory properties at the time of use deteriorate, and also the handling becomes poor during preparation of the lotion. Therefore, the blending amount of sodium hyaluronate is
It is preferably 0.01 to 10% by weight, more preferably 0.01 to 3% by weight, based on the total amount of the skin external preparation. Although 4-methoxysalicylic acid was used in this example, sodium hyaluronate also has a whitening effect-enhancing effect on other alkoxysalicylic acids and / or salts thereof according to the present invention, and chondroitin. As for other acidic mucopolysaccharides such as sodium sulfate, a whitening effect-enhancing effect was observed as in the case of sodium hyaluronate.

[Table 2] ──────────────────────────────────── Content of the sample lotion (% by weight) Comparative Example f Example 5 Example 6 Example 6 Example 7 Example 8 Example 9 ──────────────────────────────── ───── 4-Methoxysalicylic acid 0.3 0.3 0.3 0.3 0.3 0.3 Placental extract 0.5 0.5 0.5 0.5 0.5 0.5 Sodium hyaluronate 0.0 0.01 0.1 0.5 3.0 10.0 ───────────────── ─────────────────── [Effect] Whitening effect ○ ◎ ◎ ◎ ◎ ◎ ◎ Sensory and usability ◎ ◎ ◎ ◎ ◎ ○ × ────────── ──────────────────────────

Further, tocopherol acetate, methylparaben, ethylparaben, and disodium salt of ethylenediaminetetraacetic acid shown in Examples 10 to 13 of Table 3 were examined. As a result, a remarkable whitening effect-enhancing action was observed in all Examples. Was given. In addition, vitamin E esters other than Examples 10 to 13, para-aminobenzoic acid esters,
The alkylenediaminecarboxylic acid derivative also had a whitening enhancing effect on the alkoxysalicylic acid and / or its salt of the present invention. The amount of these vitamin E esters and / or para-aminobenzoic acid esters and / or alkylenediaminecarboxylic acid derivative is preferably 0.01 to 100 parts by weight based on the total amount of the skin external preparation.
It was 3% by weight, more preferably 0.05 to 0.3% by weight. When the content was 0.01% by weight or less, the whitening effect was not enhanced, and even when it was added in excess of 3% by weight, the enhancement of whitening effect commensurate with the increased amount was not observed.

[Table 3] ──────────────────────────────────── Content of the sample (% by weight) Comparative Example f Example 10 Example 11 Example 12 Example 12 Example 13 ─────────────────────────────────── ── 4-methoxysalicylic acid 0.3 0.3 0.3 0.3 0.3 placental extract 0.5 0.5 0.5 0.5 0.5 tocopherol acetate 0.0 0.5 0.0 0.0 0.0 methylparaben 0.0 0.0 0.5 0.0 0.0 ethylparaben 0.0 0.0 0.0 0.5 0.0 ethylenediaminetetraacetic acid 0.0 0.0 0.0 0.0 0.5 disodium salt ──────────────────────────────────── Whitening effect ○ ◎ ◎ ◎ ◎ ◎ ─────── ─────────────────────────────

The skin external preparations of Examples 14 to 27 below were prepared by the respective methods, and the whitening effect test was carried out in the same manner as in Examples 1 to 4. All of the skin external preparations showed excellent whitening effect. Moreover, no abnormalities were observed on the skin, and the external preparation for skin was highly safe. In addition, in the following prescriptions, the compounding amounts are all% by weight.

Example 14 Cream A cream was prepared according to the following formulation. The preparation method was as follows: placenta extract, 4-methoxysalicylic acid potassium salt, propylene glycol, caustic potash and ethylenediaminetetraacetic acid tetrasodium salt were added to ion-exchanged water and dissolved.
It was kept at ℃ (water phase). Other ingredients are mixed and dissolved by heating and kept at 70 ° C (oil phase), the oil phase is gradually added to the aqueous phase, preliminarily emulsified at 70 ° C, homogenized with a homomixer, and then well mixed. While cooling to 30 ° C. Stearic acid 6.0 Cetostearyl alcohol 3.0 Isopropyl myristate 18.0 Glycerine monostearate 3.0 Propylene glycol 10.0 4-Methoxy salicylate potassium salt 15.0 Caustic potassium 0.2 Ethylenediaminetetraacetic acid tetrasodium salt 0 .01 Tocopherol acetate 0.1 Placenta extract 2.0 Butylparaben Appropriate amount Fragrance Appropriate amount Ion-exchanged water Residual

Example 15 Cream A cream was prepared according to the following formulation. As a preparation method, propylene glycol, ethylenediaminetetraacetic acid disodium salt and a placenta extract were added to ion-exchanged water and dissolved, and the mixture was kept at 70 ° C (aqueous phase). Other ingredients are mixed and dissolved by heating and kept at 70 ° C (oil phase), the oil phase is gradually added to the aqueous phase, preliminarily emulsified at 70 ° C, homogenized with a homomixer, and then well mixed. While cooling to 30 ° C. Stearic acid 5.0 Sorbitan monostearate 2.5 Polyoxyethylene (20 mol) sorbitan monostearate 1.5 Propylene glycol 10.0 3-Isobutoxysalicylic acid 4.0 Glycerin trioctanoate 10.0 Squalene 5.0 Octyl paradimethylaminobenzoate 3.0 Disodium salt of ethylenediaminetetraacetic acid 0.01 Ethylparaben 0.3 Placental extract 0.5 Perfume proper amount Ion-exchanged water residual

Example 16 Cream A cream was prepared in the same manner as in Example 15 according to the following formulation. Stearyl alcohol 7.5 Stearic acid 1.5 Hydrogenated lanolin 2.0 Squalane 5.0 2-Octyldodecyl alcohol 6.0 Polyoxyethylene (25 mol) cetyl ether 3.0 Glycerin monostearate 2.0 Propylene glycol 5.0 Sodium hyaluronate 0.1 Octyl cinnamate 4.0 4-Methoxysalicylic acid 3.0 Ethylenediaminetetraacetic acid disodium salt 0.03 Ethylparaben 0.3 Placental extract 0.7 Perfume proper amount Ion-exchanged water residue

Example 17 Cream A cream was prepared in the same manner as in Example 15 according to the following formulation. Stearic acid 6.5 Sorbitan monostearate 2.0 Polyoxyethylene (20 mol) sorbitan monostearate 1.5 Propylene glycol 10.0 5-Ethoxysalicylic acid 8.5 Glycerin trioctanoate 10.0 Squalene 5 0.0 Sodium hyaluronate 1.0 Ethylenediaminetetraacetic acid trisodium salt 0.01 Glucose 0.5 Ethylparaben 0.3 Placental extract 3.0 Fragrance Suitable amount Ion-exchanged water Residual

Example 18 Cream A cream was prepared in the same manner as in Example 15 according to the following formulation. Stearyl alcohol 5.5 Stearic acid 2.5 Hydrogenated lanolin 2.0 Squalane 5.0 2-Octyldodecyl alcohol 6.0 Polyoxyethylene (25 mol) cetyl ether 3.0 Glycerin monostearate 2.0 Propylene glycol 5.0 4-methoxysalicylic acid 4.0 Glycerin 5.0 Sodium bisulfite 0.03 Ethylparaben 0.3 Placental extract 0.5 Perfume proper amount Ion-exchanged water residual

Example 19 Cream A cream was prepared in the same manner as in Example 15 according to the following formulation. Stearyl alcohol 5.0 Stearic acid 2.5 Hydrogenated lanolin 2.5 Squalane 5.0 2-Octyldodecyl alcohol 6.0 Polyoxyethylene (25 mol) cetyl ether 3.0 Glycerin monostearate 2.0 Propylene glycol 7.0 Sodium L-ascorbate 0.5 3-Methoxysalicylic acid 0.8 Sodium bisulfite 0.03 Ethylparaben 0.3 Placental extract 0.3 Perfume proper amount Ion-exchanged water residual

Example 20 Cream A cream was prepared in the same manner as in Example 15 according to the following formulation. Stearyl alcohol 6.0 Stearic acid 3.0 Hydrogenated lanolin 2.0 Squalane 5.0 2-Octyldodecyl alcohol 6.0 Polyoxyethylene (25 mol) cetyl ether 3.0 Glycerin monostearate 2.0 Propylene glycol 5.0 5-propoxysalicylic acid 0.05 Vitamin A palmitate 0.3 Sodium bisulfite 0.03 Ethylparaben 0.3 Placental extract 0.1 Perfume proper amount Ion-exchanged water balance

Example 21 Emulsion An emulsion was prepared according to the following formulation. The preparation method is to dissolve the carboxyvinyl polymer in a small amount of ion-exchanged water (A
Phase), polyethylene glycol in the remaining ion-exchanged water 1
500, triethanolamine and sodium sulfite were added, dissolved by heating and kept at 70 ° C. (aqueous phase). Other ingredients are mixed, heated and melted and kept at 70 ° C (oil phase), the oil phase is added to the aqueous phase for preliminary emulsification, phase A is added and the mixture is homogenized with a homomixer, while stirring well. Cooled to 30 ° C. Stearic acid 2.0 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 Sodium hyaluronate 05 4-methoxysalicylic acid 2.0 Carboxyvinyl polymer 0.05 (Brand name: Carbopol 941, BF Goodrich Chemical company) Sodium bisulfite 0.01 Ethylparaben 0.3 Placental extract 1.0 Perfume proper amount Ion exchange water Remnant

Example 22 Emulsion An emulsion was prepared in the same manner as in Example 21 with the following formulation. Stearic acid 2.5 Cetyl alcohol 1.0 Vaseline 5.0 Liquid paraffin 10.0 Polyoxyethylene (10 mol) monooleate 2.0 Polyethylene glycol 1500 3.0 Triethanolamine 1.0 3-Methoxysalicylic acid 5 .0 Glycyrrhizic acid 0.5 Amino acid 0.3 Carboxyvinyl polymer 0.05 (trade name: Carbopol 941, BF Goodrich Chemical company) Sodium bisulfite 0.01 Ethylparaben 0.3 Placental extract 2.0 Perfume suitable amount Ion-exchanged water residue

Example 23 Emulsion An emulsion was prepared according to the following formulation. As for the preparation method, the oil phase part and the water phase part were each melted at 70 ° C., the water phase part was mixed with the oil phase part, the mixture was emulsified with an emulsifier, and then cooled to 30 ° C. with a heat exchanger. [Oil phase part] Stearyl alcohol 2.0 Squalene 2.0 Vaseline 2.5 Deodorizing liquid lanolin 1.5 Evening primrose oil 2.0 Isopropyl myristate 5.0 Glycerin monooleate 2.0 Polyoxyethylene (60 mol) Curing Castor oil 2.0 Tocopherol acetate 0.05 4-Butoxysalicylic acid 2.0 Ethylparaben 0.2 Butylparaben 0.1 Perfume Suitable amount [Aqueous phase part] Glycerin 5.0 Sodium hyaluronate 0.01 Carboxyvinyl polymer 0. 2 (Brand name: Carbopol 941, BF Goodrich Chemical company) Potassium hydroxide 0.2 Sodium bisulfite 0.01 Placenta extract 0.5 Purified water Residual

Example 24 Emulsion An emulsion was prepared in the same manner as in Example 23 with the following formulation. [Oil phase part] Stearyl alcohol 1.4 Squalene 2.0 Vaseline 2.5 Deodorizing liquid lanolin 1.5 Evening primrose oil 2.0 Isopropyl myristate 5.5 Glycerin monooleate 2.0 Polyoxyethylene (60 mol) Curing Castor oil 1.5 Tocopherol acetate 0.05 5-Methoxysalicylic acid 0.5 Ethylparaben 0.2 Butylparaben 0.1 Perfume Suitable amount [Aqueous phase part] Glycerin 5.0 Sodium chondroitin sulfate 0.01 Carboxyvinyl polymer 0. 2 (Brand name: Carbopol 941, BF Goodrich Chemical company) Potassium hydroxide 0.2 Citric acid 0.01 Sodium citrate 0.1 Placental extract 0.5 Purified water Residual

Example 25 Jelly A jelly was prepared according to the following formulation. As for the preparation method, Carbopol 940 was uniformly dissolved in ion-exchanged water (aqueous phase). Polyoxyethylene (50 mol) oleyl ether was dissolved in 95% ethanol and added to the aqueous phase. Further, other components were added, and finally, caustic soda and L-arginine were added to neutralize and thicken. [Formulation] 95% ethanol 10.0 Dipropylene glycol 12.5 Polyoxyethylene (50 mol) oleyl ether 2.0 Carboxyvinyl polymer 1.0 (trade name: Carbopol 940, BF Goodrich Chemical company) 4-propoxysalicylic acid 0.05 Caustic soda 0.15 L-Arginine 0.1 2-Hydroxy-4-methoxybenzophenone 0.05 Sodium sulfonate Methylparaben 0.2 Ethylenediaminetetraacetate ・ 3 sodium ・ 2 water 0.05 Placental extract 0.5 Perfume Appropriate amount Ion-exchanged water Residual

Example 26 Beauty Serum A beauty essence was prepared according to the following formulation. As for the preparation method, phase A and phase C were uniformly dissolved, and phase A was added to phase C to solubilize it. Then, phase B was added and dissolved. [Phase A] 95% ethanol 10.0 Polyoxyethylene (20 mol) octyldodecanol 1.1 Methylparaben 0.2 Pantotenyl ethyl ether 0.1 4-Methoxysalicylic acid 0.05 [Phase B] Potassium hydroxide 0. 1 [Phase C] Glycerin 5.0 Dipropylene glycol 10.0 Sodium bisulfite 0.03 Carboxyvinyl polymer 0.2 (trade name: Carbopol 940, BF Goodrich Chemical company) Placenta extract 0.5 Purified water Residue

Example 27 Pack A pack was prepared according to the following formulation. The preparation method is A
Phase B, Phase B, and Phase C were uniformly dissolved, and Phase B was added to Phase A to solubilize it, and then Phase C was added to fill it. [Phase A] Dipropylene glycol 6.0 Polyoxyethylene (60 mol) hydrogenated castor oil 5.0 [Phase B] 3-methoxysalicylic acid 1.3 4-methoxysalicylic acid 1.5 5-methoxysalicylic acid 0.7 Olive oil 5 0.0 Tocopherol acetate 0.2 Ethylparaben 0.2 Perfume Suitable amount [Phase C] Polyvinyl alcohol (saponification degree 90, polymerization degree 2,000) 13.0 Ethanol 7.0 Placental extract 0.5 Sodium hydrogen sulfite 0.03 Purified water residue

Example 28 Powder-containing pack A powder-containing pack was prepared according to the following formulation. The preparation method is to uniformly dissolve the water phase and the alcohol phase at room temperature,
The alcohol phase was added to the aqueous phase and mixed uniformly. [Alcohol phase] 95% Ethanol 10.0 Propylene glycol 5.0 4-Methoxysalicylic acid 5.0 4-Ethoxysalicylic acid 5.0 Fragrance Suitable amount Coloring material Suitable amount [Water phase] Zinc white 25.0 Kaolin 20.0 Glycerin 5.0 Methylparaben 0.2 Placental extract 0.1 Ion-exchanged water Residual

Example 29 The emulsion A component is heated to 70 ° C. and dissolved. After the B component is heated and dissolved at 70 ° C., the A component is added thereto and emulsified. Then, the C component was added and uniformly mixed, and then heat exchanged to obtain an emulsion. This emulsion was excellent in anti-pigmentation effect, safety, and feeling in use. A. Cetanol 1.5 Stearic acid 1.0 Palmitic acid 1.2 Lanolin 3.0 Squalane 4.0 Olive oil 2.0 Oleyloylate 2.0 Dimethylpolysiloxane (6cs) 3.0 Glyceryl monooleate 2.0 POE (50) Oleyl ether 1.0 Preservative Amount Perfume Amount B. Propylene glycol 5.0 Glycerin 2.0 PEG1500 2.0 Potassium hydroxide 0.08 Sodium cetyl sulfate 0.05 Placental extract 5.0 Carboxyvinyl polymer 0.15 Ethanol 3.0 Purified water balance C. 4-Methoxysalicylic acid sodium salt 20.0

Example 30 Lotion A lotion was obtained by stirring and mixing the following ingredients. This lotion was excellent in anti-pigmentation effect, safety, and feeling in use. 4-Methoxysalicylic acid 10.0% Hydroquinone-β-D- (N-acetylglucosamine) 0.1 Placenta extract 0.01 Ethanol 9.0 POE (20) oleyl ether 1.0 Preservative proper amount Perfume proper amount Purification Water balance

Example 31 Emulsion A component is heated and dissolved at 70 ° C. After the B component is heated and dissolved at 70 ° C., the A component is added thereto and emulsified. C was added to the mixture to uniformly mix it, and then heat exchange was performed to obtain an emulsion. This emulsion was excellent in anti-pigmentation effect, safety, and feeling in use. A. Cetanol 1.5 Stearyl acid 1.0 Palmitic acid 1.2 Lanolin 3.0 Squalane 4.0 Olive oil 2.0 Oleyloylate 2.0 Dimethylpolysiloxane (6cs) 3.0 Glyceryl monooleate 2.0 POE (50) Oleyl ether 1.0 Preservative Amount Perfume Amount B. Propylene glycol 5.0 Glycerin 2.0 PEG1500 2.0 Potassium hydroxide 0.08 Sodium cetyl sulfate 0.05 Placental extract 5.0 Carboxyvinyl polymer 0.15 Ethanol 3.0 Purified water balance C. 5-methoxysalicylic acid calcium salt 0.01

[0058]

The external preparation for skin of the present invention prevents or ameliorate abnormal deposition of melanin pigment on the epidermis by the action of suppressing the production of melanin based on the inhibition of tyrosinase activity of alkoxysalicylic acid and / or its salt, and extracts the placenta. It is a skin external preparation that enhances the whitening effect of the alkoxysalicylic acid by a substance and is highly safe for the skin. The whitening effect of the external preparation for skin of the present invention is acidic mucopolysaccharide,
It is further enhanced by vitamin E esters, para-aminobenzoic acid esters and alkylenediaminecarboxylic acid derivatives.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Reference number within the agency FI technical display location // (A61K 31/60 35:50) (72) Inventor Minoru Fukuda Shinba, Kohoku-ku, Yokohama-shi, Kanagawa Town 1050 Shiseido Daiichi Research Center (72) Inventor Rumiko Kai 1050 Shinbacho, Kohoku-ku, Yokohama-shi Kanagawa Shiseido Daiichi Research Center

Claims (7)

[Claims] 1. An external skin preparation containing a placenta extract and one or more of alkoxysalicylic acid represented by the general formula (A) and / or a salt thereof. General formula (A): (In the formula, R represents an alkoxy group.) 2. The external skin preparation according to claim 1, wherein the alkoxy group is a methoxy group. 3. The external preparation for skin according to claim 1, wherein the alkoxy group is an ethoxy group. 4. The external preparation for skin according to any one of claims 1 to 3, which contains one or more acidic mucopolysaccharides. 5. The external skin preparation according to any one of claims 1 to 4, wherein one or more vitamin E esters are blended. 6. The external preparation for skin according to any one of claims 1 to 5, which contains one or more paraoxybenzoic acid esters. 7. The external skin preparation according to any one of claims 1 to 6, further comprising an alkylenediaminecarboxylic acid derivative.