JP2006008630A - Skin preparation for external use - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a skin preparation for external use which is one containing a stably compounded proteolytic enzyme and having long-term storability and a high bleaching effect. <P>SOLUTION: The skin preparation for external use is prepared by formulating subtilisin or crosslinked subtilisin with a water-soluble polymer and an alkoxysalicylic acid or a salt thereof. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to an external preparation for skin, and more particularly to an external preparation for skin excellent in whitening effect, which stably contains a proteolytic enzyme.

  Skin pigmentation, freckles, and other pigmentations are caused by hormonal abnormalities and ultraviolet light stimulation, resulting in increased melanin production in epidermal pigment cells and excessive deposition of melanin in the epidermis. Therefore, in order to prevent spots and freckles, for example, L-ascorbic acid or a derivative thereof, glutathione, hydroquinone glycoside, tranexamic acid, alkoxysalicylic acid and a salt thereof, a whitening cosmetic containing a substance that suppresses the production of melanin. However, dullness due to accumulation of keratinocytes containing old melanin could not be improved only by suppressing melanin production. Therefore, cosmetics containing a proteolytic enzyme have been proposed in order to remove keratinocytes containing old melanin. For example, Patent Document 1 describes a cosmetic containing an ascorbic acid derivative and a proteolytic enzyme. However, the proteolytic enzyme is very unstable in a system in which water is blended, and rapidly decomposes or deactivates and cannot exert a sufficient effect at the time of use.

  Proteolytic enzyme removes protein-based dirt and old keratinocytes and other skin cells to improve skin dullness and texture, and to treat skin diseases. It has been conventionally used in various detergents such as products, but due to its instability in an aqueous medium, its dosage form has been limited to powders mainly containing no water.

  Methods for enhancing the stability of proteolytic enzymes in aqueous media include, for example, liquid cleaning compositions containing surfactants and detergent enzymes, combinations of triethanolamine and sodium chloride as a detergent builder, and ethanol or A method of blending polyhydric alcohol (Patent Document 2), a method of immobilizing serine protease on an insoluble carrier (Patent Document 3), a method of blending with a specific polymer copolymer (Patent Document 4), etc. It has been known.

However, all of these methods showed a certain effect on the stabilization of the enzyme, but could not provide a skin external preparation that can be stored for a long period of time and has a high whitening effect.
JP 2002-284665 A JP-A-4-54720 JP-A-8-38175 JP-A-11-246894

  In view of the circumstances as described above, the present invention provides a skin external preparation that can be stably stored for a long period of time by stably incorporating a proteolytic enzyme in a skin external preparation and has a high whitening effect. It is the purpose.

  The inventor of the present invention can stably maintain the enzyme activity for a long period of time in an aqueous medium by blending subtilisin or a subtilisin crosslinked product (hereinafter also referred to as subtilisin) as a proteolytic enzyme together with a water-soluble polymer. In addition, the topical skin preparation containing subtilisin has a very high exfoliating effect, and further, alkoxysalicylic acid or a salt thereof as a whitening agent is blended with subtilisin etc. It has been found that a high whitening effect that is synergistically superior to the case of using it can be achieved, and the present invention has been completed.

  The external preparation for skin of the present invention is characterized by containing subtilisin or a subtilisin cross-linked product, a water-soluble polymer, and alkoxysalicylic acid or a salt thereof.

  The water-soluble polymer used in the external preparation for skin of the present invention is preferably one or more selected from the group consisting of xanthan gum, carboxymethylcellulose and carboxyvinyl polymer. By blending these water-soluble polymers together with subtilisin or the like, subtilisin or the like can be particularly remarkably stabilized.

  Since the external preparation for skin of the present invention contains subtilisin or a subtilisin cross-linked product and a water-soluble polymer, the activity of subtilisin and the like is maintained very stably even in an aqueous medium, and can be stored for a long time. High dullness can be improved.

  Furthermore, since the skin external preparation of the present invention contains alkoxysalicylic acid or a salt thereof together with subtilisin or the like, it can provide a synergistically enhanced very whitening effect.

  Therefore, it is possible to provide a skin external preparation having a high whitening effect that can be stably stored for a long period of time in any dosage form in which a proteolytic enzyme could not be blended due to inactivation of enzyme activity. It is.

  As used herein, subtilisin is a serine protease produced by a bacterium of the genus Bacillus, for example, from subtilisin BPN 'from Bacillus amyloliquefaciens, Bacillus licheniformis. Subtilisin Carlsberg, Subtilisin DY from Bacillus DY, Subtilisin amylosacharticus from Bacillus amylosachariticus, and the like.

  Moreover, in this specification, a subtilisin cross-linked product means a polymer obtained by cross-linking subtilisin. As long as the enzyme activity of subtilisin is not impaired, the crosslinking method is not particularly limited, and examples thereof include those obtained by crosslinking subtilisin with glutaraldehyde.

  In the skin external preparation of the present invention, the above subtilisin or the subtilisin cross-linked product may be blended alone or in combination of two or more. You may mix | blend a subtilisin and a subtilisin crosslinked body combining.

  The amount of subtilisin and / or the subtilisin cross-linked product in the external preparation for skin of the present invention is appropriately determined depending on the form of the external preparation for skin, the activity of the enzyme used, and the like, but is not particularly limited. It is 0.01-10 mass% with respect to the total mass, More preferably, it is 0.05-5 mass%.

  The water-soluble polymer used in the present invention is not particularly limited, but is a plant polymer such as gum arabic, gum tragagant, galactan, guar gum, caraquinan, pectin, quince seed (quince) extract, brown alga powder, xanthan gum, dextran. , Microbial polymers such as pullulan, cellulose such as methyl cellulose, nitrocellulose, ethyl cellulose, methyl hydroxypropyl cellulose, hydroxyethyl cellulose, cellulose sulfate, hydroxypropyl cellulose, carboxymethyl cellulose, crystalline cellulose, cellulose powder, polyvinyl alcohol, polyvinyl methyl Ethers, polyvinyl pyrrolidone, vinyl polymers such as carboxyvinyl polymer, polyacrylic acid and its salts, polyacrylimide, etc. Acrylic polymers and the like. Among these, particularly when xanthan gum, carboxymethyl cellulose, or carboxyvinyl polymer is used, subtilisin and the like can be more remarkably stabilized, and carboxyvinyl polymer is most preferable.

  In the skin external preparation of the present invention, the above water-soluble polymer may be blended singly or in combination of two or more.

  The blending amount of the water-soluble polymer in the external preparation for skin of the present invention is appropriately determined depending on the form of the external preparation for skin and the like, and is not particularly limited, but is preferably 0.01 with respect to the total mass of the external preparation for skin. It is -5.0 mass%, More preferably, it is 0.1-1.0 mass%.

  Examples of the alkoxysalicylic acid used in the external preparation for skin of the present invention include 3-methoxysalicylic acid, 4-methoxysalicylic acid, 5-methoxysalicylic acid, and the salts thereof include, for example, sodium, potassium, magnesium, and triethanol. Examples of each salt include amines.

  In the skin external preparation of the present invention, the above alkoxysalicylic acid or a salt thereof may be blended singly or in combination of two or more. You may mix | blend alkoxy salicylic acid and its salt combining.

  The amount of the above-mentioned alkoxysalicylic acid and / or salt thereof in the external preparation for skin of the present invention is appropriately determined depending on the form of the external preparation for skin, etc., and is not particularly limited, but preferably, with respect to the total mass of the external preparation for skin And 0.01 to 20% by mass, more preferably 0.1 to 10% by mass.

  In the present specification, the “skin external preparation” is not particularly limited as long as it is applied to the outer skin, and includes cosmetics, pharmaceuticals, quasi drugs and the like. Moreover, the dosage form is also an aqueous solution system, a solubilization system, an emulsification system, an oil liquid system, a gel system, a paste system, an ointment system, a powder system, an aerosol system, a water-oil two-layer system, and a water-oil-powder three-layer system. Including any dosage form. Moreover, what was carry | supported by the sheet-like base is also included. In particular, the effect of the present invention is remarkable in a water-containing preparation.

  Moreover, the usage form is also arbitrary, for example, it can be used for skin care cosmetics such as lotion, milky lotion, cream and pack, makeup cosmetics such as foundation, aromatic cosmetics, bath preparations, cleaning agents, etc. Of course, it is not limited to.

  The external preparation for skin of the present invention contains, in addition to the above-described essential constituents, other optional components that are usually used in external preparations for skin, such as cosmetics and pharmaceuticals, as appropriate, depending on the intended dosage form. Can be produced by conventional methods. For example, the external preparation for skin of the present invention can be prepared by blending the above essential blending components and one or more of the following components.

  Examples of the ultraviolet absorber include paraaminobenzoic acid (hereinafter abbreviated as PABA), PABA monoglycerin ester, N, N-dipropoxy PABA ethyl ester, N, N-diethoxy PABA ethyl ester, N, N-dimethyl PABA ethyl ester, Benzoic acid UV absorbers such as N, N-dimethyl PABA butyl ester and N, N-dimethyl PABA methyl ester, anthranilic acid UV absorbers such as homomenthyl-N-acetylanthranilate, amyl salicylate, menthyl salicylate, homo Salicylic acid UV absorbers such as menthyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate, p-isopropanol phenyl salicylate, octyl cinnamate, ethyl-4-isopropylcinnamate, methyl-2,5-diisopropylcinnamate, ethyl-2 , 4-Diisopropylcin Mate, 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, 2-ethylhexyl-α-cyano-β-phenylcinnamate, Cinnamic acid UV absorbers such as glyceryl mono-2-ethylhexanoyl-diparamethoxycinnamate, methyl bis (trimethylsiloxane) silylisopentyl trimethoxycinnamate, 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'-methyl Phenylbenzotriazole, dibenzalazine, dianisoylmethane, 4-methoxy-4'-t-butyldibenzoylmethane, 5- (3,3-dimethyl-2-norbornylidene) -3-pentan-2-one, dimorpholinopyrida Dinone etc. are mentioned, Arbitrary 1 type, or 2 or more types can be used.

  Examples of the ultraviolet scattering agent include powders of titanium oxide, fine particle titanium oxide, zinc oxide, fine particle zinc oxide, iron oxide, fine particle iron oxide, cerium oxide, and the like.

  As these ultraviolet scattering agents, needle-like, spindle-like, spherical and granular powders are usually used. A fine particle powder having a particle size of 0.1 μm or less is preferred.

  Silicone treatment such as methyl hydrogen polysiloxane and silane coupling agent; metal soap treatment; UV scattering agent that has been hydrophobized by fluorine treatment such as perfluoroalkyl phosphate diethanolamine salt and perfluoroalkyl silane, dextrin fatty acid ester treatment, etc. Is also preferable.

  Examples of liquid 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, southern castor oil, castor oil, linseed oil , Safflower oil, cottonseed oil, eno oil, soybean oil, peanut oil, tea seed oil, kaya oil, rice bran oil, cinnagiri oil, Japanese kiri oil, jojoba oil, germ oil, triglycerin and the like.

  Examples of the solid fat include cacao butter, palm oil, horse fat, hydrogenated palm oil, palm oil, beef tallow, sheep fat, hydrogenated beef tallow, palm kernel oil, pork fat, beef bone fat, owl kernel oil, hydrogenated oil, cattle Leg fats, moles, hydrogenated 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, lanolin fatty acid isopropyl, hexyl laurate, and reduced lanolin. , Jojoballow, 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.

  Examples of the hydrocarbon oil include liquid paraffin, ozokerite, squalane, pristane, paraffin, ceresin, squalene, petrolatum, microcrystalline wax, polyethylene wax, and Fischer-Tropsch wax.

  Examples of higher fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, undecylenic acid, toluic acid, linoleic acid, linolenic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and the like. Is mentioned.

  Examples of higher alcohols include linear alcohols (eg, lauryl alcohol, cetyl alcohol, stearyl alcohol, behenyl alcohol, myristyl alcohol, oleyl alcohol, cetostearyl alcohol); branched chain alcohols (eg, monostearyl glycerin ether (batyl alcohol) ), 2-decyltetradecinol, lanolin alcohol, cholesterol, phytosterol, hexyldodecanol, octyldodecanol and the like.

  Synthetic ester oils include isopropyl myristate, cetyl octanoate, octyldodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, hexyl decyl dimethyloctanoate, cetyl lactate, myristyl lactate Lanolin acetate, isocetyl stearate, isocetyl isostearate, cholesteryl 12-hydroxystearate, ethylene glycol di-2-ethylhexanoate, dipentaerythritol fatty acid ester, monoisostearate N-alkyl glycol, neopentyl glycol dicaprate, apple Acid diisostearyl, di-2-heptylundecanoic acid glycerin, tri-2-ethylhexanoic acid trimethylolpropane, triisostearic acid trimethylo Propane, tetra-2-ethylhexanoate pentaerythritol, glycerol tri-2-ethylhexanoate, glycerol trioctanoate, glycerol triisopalmitate, trimethylolpropane triisostearate, cetyl 2-ethylhexanoate, 2-ethylhexyl palmi Tate, glyceryl trimyristate, glyceride tri-2-heptylundecanoate, castor oil fatty acid methyl ester, oleyl oleate, acetoglyceride, 2-heptylundecyl palmitate, 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 Le, 2-ethylhexyl succinate, triethyl citrate, polyoxyethylene-polyoxypropylene random polymer methyl ether.

  Examples of the silicone oil include linear polysiloxanes (for example, dimethylpolysiloxane, methylphenylpolysiloxane, diphenylpolysiloxane, etc.); cyclic polysiloxanes (for example, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexyl). And silicone resins that form a three-dimensional network structure, various modified polysiloxanes (amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxane, fluorine-modified polysiloxane, etc.) It is done.

  Other examples include humectants such as polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, and maltitol; lower alcohols such as ethanol; antioxidants such as butylhydroxytoluene, tocopherol, and phytin; Antibacterial agents such as benzoic acid, salicylic acid, sorbic acid, paraoxybenzoic acid alkyl ester, hexachlorophene; acyl sarcosine acid (eg, lauroyl sarcosine sodium), organic acids such as glutathione, citric acid, malic acid, tartaric acid, lactic acid; vitamin A and Derivatives, vitamin B6 hydrochloride, vitamin B6 tripalmitate, vitamin B6 dioctanoate, vitamin B2 and derivatives thereof, vitamin B such as vitamin B12, vitamin B15 and derivatives thereof, ascorbi Vitamin C such as acid, ascorbic acid sulfate (salt), ascorbic acid phosphate (salt), ascorbic acid dipalmitate, vitamin E such as α-tocopherol, β-tocopherol, δ-tocopherol, vitamin E acetate, Vitamins such as vitamin D, vitamin H, pantothenic acid, panthetin; nicotinamide, benzyl nicotinate, γ-oryzanol, allantoin, glycyrrhizic acid (salt), glycyrrhetinic acid and its derivatives, hinokitiol, bisabolol, eucarptone Saponins such as thymol, inositol, saikosaponin, carrot saponin, loofah saponin, muclodisaponin, various drugs such as pantothenyl ethyl ether, ethinyl estradiol, cephalanthin, placenta extract, Ghishi, Clara, Kouhone, Orange, Sage, Yarrow, Zeniahoi, Assembly, Thyme, Spruce, Spruce, Birch, Sugina, Loofah, Maronier, Yukinoshita, Arnica, Lily, Mugwort, Peonies, Aloe, Gardenia, Sawara, Hawthorn Extract Hypericum perforatum extract, Iris in extract, Acacia yak extract, Ginkgo biloba extract, Ichiki-jako extract, Fennel extract, Oolong tea extract, Water lily extract, Ages extract, Emperor extract, Ogon extract, Oat extract, Licorice extract, Licorice extract, Gardenia extract, black tea extract, sesame extract, tormentilla extract, rose extract, loofah extract, peppermint extract, rosemary extract, royal jelly extract, etc. Extract, pigment, sorbitan monolaurate, sorbitan monopalmitate, sorbitan sesquioleate, sorbitan trioleate, polyoxyethylene sorbitan monolaurate, polyoxethylene sorbitan monostearate, polyethylene glycol monooleate, polyoxyethylene alkyl Nonionic active agents such as ether, polyglycol diether, lauroyl diethanolamide, fatty acid isopropanol amide, maltitol hydroxy fatty acid ether, alkylated polysaccharide, alkyl glucoside, sugar ester, stearyltrimethylammonium chloride, benzalkonium chloride, laurylamine Cationic surfactants such as oxide, sodium palmitate, sodium laurate, sodium laurate Anionic surfactants such as potassium, lauryl sulfate, alkyl sulfate triethanolamine ether, funnel oil, linear dodecyl benzene sulfate, polyoxyethylene hydrogenated castor oil maleic acid, acylmethyl taurine, amphoteric surfactant, neutralizing agent, Examples include antioxidants such as δ-tocopherol and butylhydroxytoluene, and preservatives such as phenoxyethanol and paraben.

  Furthermore, the skin external preparation of this invention may contain the other arbitrary components which have a whitening effect other than the alkoxy salicylic acid or its salt. For example, hydroquinone glycosides, tranexamic acid or derivatives thereof, alkyl resorcinols such as resorcin, 4-n-butylresorcinol, and resorcins and derivatives thereof such as salts thereof, glutathione, kojic acid, ellag Examples include acids, and further, herbal medicines having a whitening effect.

  Examples of hydroquinone glycosides include hydroquinone α-D-glucose, hydroquinone β-D-glucose (also referred to as “arbutin”), hydroquinone α-L-glucose, hydroquinone β-L-glucose, hydroquinone α-D-galactose, Hexasaccharide glycosides such as hydroquinone β-D-galactose, hydroquinone α-L-galactose, hydroquinone β-L-galactose; hydroquinone α-D-ribose, hydroquinone β-D-ribose, hydroquinone α-L-ribose, Five-carbon sugar glycosides such as hydroquinone β-L-ribose, hydroquinone α-D-arabinose, hydroquinone β-D-arabinose, hydroquinone α-L-arabinose, hydroquinone β-L-arabinose; hydroquinone α-D-glucosami , Hydroquinone β-D-glucosamine, hydroquinone α-L-glucosamine, hydroquinone β-L-glucosamine, hydroquinone α-D-galactosamine, hydroquinone β-D-galactosamine, hydroquinone α-L-galactosamine, hydroquinone β-L-galactosamine Aminoquinoside glycosides such as hydroquinone α-D-glucuronic acid, hydroquinone β-D-glucuronic acid, hydroquinone α-L-glucuronic acid, hydroquinone β-L-glucuronic acid, hydroquinone α-D-galacturonic acid, hydroquinone β -D-galacturonic acid, hydroquinone α-L-galacturonic acid, uronic acid carbohydrate glycosides such as hydroquinone β-L-galacturonic acid and the like, further, ester forms such as acetylated products, ethers such as methylated products Na Like derivatives of.

  Examples of tranexamic acid or derivatives thereof include tranexamic acid, dimers of tranexamic acid [eg, trans-4- (trans-aminomethylcyclohexanecarbonyl) aminomethylcyclohexanecarboxylic acid, etc.], tranexamic acid and hydroquinone. Esters (eg, trans-4-aminomethylcyclohexanecarboxylic acid 4′-hydroxyphenyl ester, etc.), esters of tranexamic acid and gentisic acid [eg, 2- (trans-4-aminomethylcyclohexylcarbonyloxy) ) -5-hydroxybenzoic acid and its salts, etc.], an amide of tranexamic acid [for example, trans-4-aminomethylcyclohexanecarboxylic acid methylamide and its salt, trans-4- (p-methoxybenzoyl) a Roh methylcyclohexane carboxylic acid and its salts, trans-4-guanidinomethyl cyclohexane carboxylic acid and salts thereof, etc.] and the like.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated concretely, this invention is not limited to the following Example.

Examination of effect of water-soluble polymer on enzyme activity of subtilisin or subtilisin cross-linked product Each sample was prepared with the composition shown in Table 1. All compounding amounts are expressed in mass% based on the total amount of the sample:

Protease type VIII (Subtilisin Carlsberg) (manufactured by Sigma) was used as a subtilisin, and a subtilisin cross-linked body fluid (manufactured by COLETICA) was used as a subtilisin cross-linked product.

  Immediately after each sample was prepared and after each sample was stored in a thermostatic bath at 50 ° C. for 1 month, the enzyme activity was measured as follows.

<Measurement of enzyme activity>
2.6 ml of 0.046 M Tris-HCl buffer (pH 8.0) and 0.3 ml of 0.01 M TAME (Np-tosyl-arginine methyl ester) (T4626 Sigma) solution were placed in a test tube and stirred. Thus, a reaction solution containing a substrate for enzyme reaction was prepared. 0.1 ml of each sample (Test Examples 1 to 4 or Comparative Examples 1 to 5) immediately after preparation or after storage for 1 month was added to the reaction solution, stirred, and immediately afterwards with a spectrophotometer (reaction rate measurement type) at a wavelength of 247 nm. The absorbance was measured over time. The proteolytic enzyme (protease) activity (dA ₂₄₇ / min) was determined from the change in absorbance over time. The enzyme residual rate was calculated from the following formula:

  As is apparent from Table 1, the enzyme activity of subtilisin and the like was very stably maintained by blending the water-soluble polymer together with the subtilisin or the subtilisin cross-linked product.

Examination of whitening effect External preparation of the present invention (Example 1) containing subtilisin or a subtilisin cross-linked product, carboxyvinyl polymer as a water-soluble polymer, and 4-methoxysalicylic acid which is alkoxysalicylic acid, in the composition shown in Table 2. And 2), and comparative samples (Comparative Examples 1 to 3). All compounding amounts are expressed in mass% with respect to the total amount of the sample:

Protease type VIII (Subtilisin Carlsberg) (manufactured by Sigma) was used as a subtilisin, and a subtilisin cross-linked body fluid (manufactured by COLETICA) was used as a subtilisin cross-linked product. Each sample was evaluated for the whitening effect (improving the state of spots and freckles and the dullness of the skin) as follows.

<Evaluation method>
10 female panels suffering from spots, freckles, and dull skin, and samples of external preparations of the present invention (Examples 1 and 2) and comparative products (Comparative Examples 1 to 3) were used on the face for 2 months. The skin condition (stain / sobacus condition and skin dullness) after continuous use was evaluated according to the following criteria.

<Evaluation criteria for the status of stains and freckles>
◎: More than 8 out of 10 panelists said that spot and freckles were improved. ○: Panel that answered that spot and freckles were improved. 6 to 7 persons out of 10. Δ: Spots and freckles were improved. Panels that answered 3 to 5 out of 10 ×: Panels that answered that spot and freckles were improved were 2 or less out of 10

<Evaluation criteria for skin dullness>
◎: More than 8 out of 10 panelists answered that skin dullness was improved. ○: 6-7 out of 10 panel responded that skin dullness was improved. △: Dull skin was improved. Panels that answered 3 to 5 out of 10 ×: Panels that answered that skin dullness was improved was 2 or less of 10

  As is apparent from Table 2, the topical preparation of the present invention (Examples 1 and 2) containing subtilisin or a subtilisin cross-linked product, a water-soluble polymer, and 4-methoxysalicylic acid was used for the state and skin of stains and freckles. Both dullness could be improved significantly. On the other hand, in Comparative Examples 1 and 2 that do not contain subtilisin or the like, skin dullness could hardly be improved, and in Comparative Example 3 that did not contain 4-methoxysalicylic acid, the state of spots and freckles could hardly be improved. .

  Below, the other formulation example of the skin external preparation of this invention is shown as an Example. All compounding amounts are expressed in mass% with respect to the total amount of the external preparation.

Example 3: Pack cosmetic ingredients Blending amount (mass%)
Subtilisin cross-linked product 0.5
Carboxyvinyl polymer 0.15
Ethanol 5.0
Dynamite Glycerin 3.0
Arbutin 3.0
4-Methoxysalicylic acid 2.0
Citric acid 0.01
Sodium citrate 0.09
Edetate trisodium 0.1
Ion exchange water

Example 4: Ingredients for wiping lotion Ingredients (mass%)
Subtilisin cross-linked product 0.5
Xanthan gum 0.5
Ethanol 5.0
1,3-butylene glycol 1.0
Tranexamic acid 3.0
4-Methoxysalicylic acid 3.0
Citric acid 0.01
Sodium citrate 0.09
Edetate trisodium 0.1
Ion exchange water

  The external preparations for skin of Examples 3 and 4 had a very high whitening effect.

Claims (2)

A skin external preparation containing subtilisin or a subtilisin cross-linked product, a water-soluble polymer, and alkoxysalicylic acid or a salt thereof. The external preparation for skin according to claim 1, wherein the water-soluble polymer is one or more selected from the group consisting of xanthan gum, carboxymethylcellulose and carboxyvinyl polymer.