JP6222894B2 - Epidermis thickener - Google Patents

Description

  The present invention relates to an epidermis thickener and an external composition for skin containing an epidermis thickener.

  The skin is always exposed to external stimuli such as ultraviolet rays, and the internal tissue is protected by always maintaining a certain thickness.

  Conventionally, retinol has been reported to suppress keratinization by inhibiting cell differentiation on the skin. In particular, it has been shown that thickening in the epidermis, densification of the stratum corneum structure in the epidermis, activation of fibroblasts in the dermis, increase in the number of cells, increase in collagen in the dermis layer, etc. (See Non-Patent Document 1).

  However, since retinol is a substance that is easily oxidized, there is a problem that stability to an aqueous preparation (lotion, essence, aqueous cream, aqueous gel, sheet mask, spray, etc.) containing a large amount of water is poor. As a method for solving this problem, a retinoid is encapsulated in a lipid bilayer made of hydrogenated phospholipid, and a hydrophobic antioxidant such as vitamin E or a derivative thereof is allowed to coexist and dispersed or emulsified in an aqueous preparation. A method for preparing an aqueous preparation has been proposed (see Patent Document 1).

  Urea has been conventionally used as a component for external preparations for skin because of its excellent moisturizing action and expecting its effect. Patent Document 2 describes that retinol or a derivative thereof is used in combination in order to enhance the feeling of use of a moisturizing skin external preparation containing urea, and in order to further improve the moisturizing property and feeling of use, Or it describes that the derivative | guide_body is mix | blended. However, urea has long been known to have a keratolytic effect as well as a moisturizing effect, and has been used as an external preparation for the treatment of keratosis abnormalities such as ichthyosis, psoriasis, and senile xeroderma. (See Patent Documents 3 to 5).

JP 2009-256268 A JP 2008-31159 A Japanese Unexamined Patent Publication No. 60-89408 JP 61-130204 A JP-A-61-200904

Journal of the Japan Cosmetic Science Society 16 (3) 172-174 (1994)

  An object of this invention is to provide an epidermis thickening promoter. The present invention also provides an external preparation for skin containing the above-mentioned epidermal thickening promoter, in particular, imparts tension and elasticity to the skin to make fine lines inconspicuous and to make the skin smooth, etc., thereby preventing aging and rejuvenating the skin. Providing skin preparations that are effective on the skin, skin preparations that are effective in promoting wound healing of skin, or skin preparations that are effective in improving symptoms of skin diseases such as pore lichen (porosity keratosis) The purpose is to do.

  The inventors of the present invention have been diligently studying to achieve the above-mentioned object, and by using a retinoid in combination with tocopherol or a derivative thereof, it is possible to promote thickening of the epidermis, and in addition to these, urea or It has been found that thickening of the epidermis can be further promoted by using glycyrrhizic acid or a salt thereof together.

  The present invention has been completed based on these findings, and includes the following embodiments.

(I) Epidermal thickening promoter (I-1) (A) Retinoid and (B) Tocopherol or a derivative thereof as an active ingredient.
(I-2) The epidermal thickening promoter according to (I-1), further comprising (C) glycyrrhizic acid or a salt thereof and (D) at least one selected from urea.
(I-3) The epidermal thickening promoter according to (I-1) or (I-2), wherein the component (A) is retinol or a retinol fatty acid ester.
(I-4) The epidermal thickening promoter according to any one of (I-1) to (I-3), wherein the component (B) is tocopherol or a tocopherol organic acid ester.
(I-5) The component (C) is at least one selected from the group consisting of dipotassium glycyrrhizinate, disodium glycyrrhizinate, trisodium glycyrrhizinate, monoammonium glycyrrhizinate, and diammonium glycyrrhizinate ( The epidermal thickening promoter according to any one of (I-1) to (I-4).

(II) Skin external preparation (II-1) A skin external preparation containing the epidermal thickening promoter described in (I-1) or (I-2).
(II-2) (A) retinoid, (B) tocopherol or derivative thereof, and (C) glycyrrhizic acid or salt thereof; or (A) retinoid, (B) tocopherol or derivative thereof, (C) glycyrrhizic acid or salt thereof And (D) an external preparation for skin containing urea as an active ingredient.
(II-2) The external preparation for skin described in (II-1), wherein the external preparation for skin is a pharmaceutical composition, a quasi-drug composition, or a cosmetic composition.

  According to the skin thickening accelerator and external preparation for skin of the present invention, the thickening of the epidermis is promoted, the skin tension and elasticity are improved, fine lines are not noticeable, and the skin texture can be adjusted. It is. Therefore, it is effective in preventing skin aging and rejuvenating. Moreover, according to the skin thickening promoter and the external preparation for skin of the present invention, the proliferation of epidermal keratinocytes is promoted, which is effective for promoting wound healing of the skin. Moreover, according to the skin thickening promoter and external preparation for skin of the present invention, it can be expected to improve skin disease symptoms such as pore lichen (porosity keratosis) and acne (comedones).

(A) Stained image of mouse skin tissue to which the test sample of Example 3 was applied, (B) Stained image of mouse skin tissue to which the test sample of the control example was applied.

(1) Skin thickening promoter The skin thickening promoter of the present invention is characterized by containing (A) a retinoid and (B) tocopherol or a derivative thereof as active ingredients. Moreover, in addition to the said (A) and (B) component, the epidermal thickening promoter of this invention contains (C) glycyrrhizic acid or its salt, and (D) at least 1 type selected from urea. Features.

  Hereinafter, these components will be described.

(A) Retinoid In the present invention, retinoid is a general term for retinol (vitamin A) and compounds similar in structure and function to the retinol. Specifically, retinol; retinol acetate, retinol propionate, retinol butyrate, retinol octylate, retinol laurate, retinol palmitate, retinol stearate, retinol myristate, retinol oleate, retinol linolenate, retinol linoleate, etc. Retinol fatty acid esters of: retinol oxides such as retinal and retinoic acid; methyl retinoic acid, ethyl retinoic acid, retinol retinoic acid, tocopherol retinoic acid (tocopherol may be any of α, β, γ, δ) ) And the like; and salts thereof. These may be used alone or in any combination of two or more.

  The retinoid is preferably retinol or a retinol fatty acid ester, more preferably a retinol fatty acid ester. Among the retinol fatty acid esters, retinol palmitate, retinol linoleate, and retinol propionate are preferable, and retinol palmitate is more preferable.

  The retinoid salt is not particularly limited as long as it is a pharmaceutically acceptable salt. For example, depending on the type of retinoid, alkali metal salts such as sodium and potassium; alkaline earth metal salts such as calcium and magnesium; ammonium salts; inorganic acid salts such as hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid; citric acid, succinic acid Organic acid salts such as acid salts, acetates, tartrates or lactates; etc. can be appropriately selected and used.

  In addition, the origin and state (presence / absence of purification) of the retinoid used in the present invention are not limited. For example, it may be liver oil obtained by extraction and purification from animals or vitamin A oil described in the Japanese Pharmacopoeia (including 30,000 vitamin A units (IU) or more per gram).

  The content ratio of the retinoid in the epidermal thickening agent is not particularly limited as long as the epidermal thickening agent containing the retinoid and at least tocopherol or a derivative thereof described later exhibits the epidermal thickening promoting action. Usually, 1 to 30% by weight, preferably 2 to 25% by weight, more preferably 4 to 20% by weight.

(B) Tocopherol or derivative thereof In the present invention, the tocopherol may be any of α-tocopherol, β-tocopherol, γ-tocopherol, and δ-tocopherol. Α-tocopherol and δ-tocopherol are preferable, and α-tocopherol is more preferable. These tocopherols may be either d-form or dl-form.

  Examples of tocopherol derivatives include tocopherol organic acid esters such as tocopherol acetate, tocopherol succinate, tocopherol nicotinate, and tocopherol linolenate. Preferred are tocopherol acetate and tocopherol nicotinate, and more preferred is tocopherol acetate. The tocopherol organic acid ester may have a salt form when the organic acid is not a monocarboxylic acid, and examples of such a salt include calcium tocopherol succinate. These tocopherol derivatives may be either d-form or dl-form.

  The above-mentioned tocopherol and derivatives thereof may be used alone or in any combination of two or more.

  The content ratio of tocopherol or a derivative thereof in the epidermal thickening agent may be a ratio such that the epidermal thickening agent containing retinoid and tocopherol or a derivative thereof exerts an epidermal thickening promoting action, and in particular, as long as it is Although it does not restrict | limit, Usually, 5-99 weight%, Preferably it is 10-80 weight%, More preferably, 15-70 weight% can be mentioned.

(C) Glycyrrhizic acid or a salt thereof In addition to the above components (A) and (B), the glycyrrhizic acid or a salt thereof can be blended with the epidermal thickening promoter of the present invention. A highly effective epidermal thickening promoter can be obtained.

  Glycyrrhizic acid is a glycoside contained in the roots of licorice (Glycyrrhiza glabra L.), a perennial of the leguminous family, and is called glycyrrhizic acid because it has a carboxyl group in the molecule. Also called glycyrrhizin.

  The salt of glycyrrhizic acid is not particularly limited as long as it is a pharmaceutically acceptable salt. Alkali metal salts such as dipotassium glycyrrhizinate, disodium glycyrrhizinate, and trisodium glycyrrhizinate; glycyrrhizic acid Examples include ammonium salts such as monoammonium and diammonium glycyrrhizinate.

  In addition, the origin and state (presence / absence of purification) of glycyrrhizic acid or a salt thereof used in the present invention are not limited. For example, a crude drug, a crude drug extract or a crude drug extract containing glycyrrhizic acid or a salt thereof may be used. For example, licorice, licorice extract, kakkonto extract, maoyu extract, Shoseiryu extract, Koshiba Mention may be made of koto extract, saiko kei edu extract, kei edu extract and the like. Preferred are glycyrrhizic acid, dipotassium glycyrrhizinate, disodium glycyrrhizinate, trisodium glycyrrhizinate, licorice and licorice extract.

  The crude drug extract can be produced, for example, by extracting the crude drug with water or an organic solvent such as ethanol, removing insolubles and drying, and a commercially available product can also be used. Examples of commercially available products include, for example, licorice dry extract (dried licorice water extract, manufactured by Nippon Powdered Chemicals), licorice flow extract (alcoholic water / ethanol flow extract, manufactured by Alps Chemicals) ), “Starritin” (enzymatic degradation licorice, manufactured by Maruzen Pharmaceutical Co., Ltd.), “Glitimine W” (containing 17.5% glycyrrhizin, manufactured by Maruzen Pharmaceutical Co., Ltd.), “licorice dried extract E” (dried licorice water extract, Matsuura Yakuhin) For example).

  In the epidermal thickening promoter of the present invention, these glycyrrhizic acids or salts thereof described above may be used alone or in any combination of two or more.

  As the content ratio of glycyrrhizic acid or a salt thereof in the epidermal thickening promoter, in addition to the components (A) and (B), the epidermal thickening agent blended with glycyrrhizic acid or a salt thereof exhibits an epidermal thickening promoting action. Such a ratio, preferably a ratio such that the epidermal thickening promoting action is enhanced as compared with the epidermal thickening promoter before blending glycyrrhizic acid or a salt thereof, and is not particularly limited as long as it is usually 0.1 to 40 wt%, preferably 10 to 35 wt%, more preferably 20 to 35 wt%.

(D) Urea The epidermal thickening promoter of the present invention can contain (D) urea in addition to the above components (A) and (B), and thus an even more effective epidermal thickening promoter. Can be obtained. Moreover, in addition to (A), (B) and (C) component, (D) urea may be mix | blended with the epidermis thickening promoter of this invention.

  As the content ratio of urea in the epidermis thickening accelerator, in addition to the components (A) and (B), a ratio such that the epidermis thickener containing urea has an effect of promoting epidermis thickening, preferably urea. The ratio is such that the epidermal thickening promoting action is enhanced as compared with the epidermal thickening promoter before blending, and is not particularly limited as long as it is, but is usually 0.1 to 90% by weight, preferably 10 to 85% by weight, More preferably, 20 to 80% by weight can be mentioned.

  The epidermal thickening promoter of the present invention may be any as long as it contains at least one of (C) component and (D) component in addition to the above components (A) and (B), or (A) and (B) components. As an active ingredient of a skin external preparation described later, it is prepared and used in the form of a skin external preparation.

(2) External preparation for skin As described above, the epidermal thickening promoter of the present invention can be used as an active ingredient of an external preparation for skin. The external preparation for skin can be used effectively in various fields in which the effects of the present invention, that is, the effect of promoting epidermal thickening and the effects derived therefrom, such as external medicines applied to humans, quasi-drugs for external use, cosmetics, etc. It is possible to use in the field. As described above, the effects derived from the action to promote epidermal thickening include the effects of improving the firmness and elasticity of the skin to make wrinkles less noticeable, the effect of smoothing the skin, and preventing skin aging and rejuvenation. The effect to promote and the effect of promoting wound healing of the skin can be exemplified.

  For this reason, the epidermis thickening promoter of the present invention may be used as it is as an external medicine, an external medicine quasi-drug, or a cosmetic, but is usually acceptable in the field of external medicine, external quasi-drug, or cosmetic. It is mixed with carriers and additives and prepared as various skin external preparations according to the purpose and application.

The external preparation for skin of the present invention exerts an action of promoting epidermal thickening by adding at least one of the components (C) and (D) to the components (A) and (B) or the components (A) and (B). As long as it contains an effective amount, the content ratio of the components (A) to (D) is not particularly limited, but the following ranges are examples of the content ratio of each component in 100% by weight of the external preparation for skin. Can be illustrated.
Component (A): 0.001 to 5% by weight, preferably 0.01 to 3% by weight, more preferably 0.1 to 1% by weight
Component (B): 0.01 to 10% by weight, preferably 0.1 to 5% by weight, more preferably 1 to 3% by weight
Component (C): 0 to 20% by weight, preferably 8 to 15% by weight, more preferably 10 to 12% by weight
Component (D): 0 to 5% by weight, preferably 0.01 to 3% by weight, more preferably 0.1 to 1% by weight.

  In addition, the external preparation for skin of the present invention includes, as other components, active substances that exert physiological action on the skin, or carriers and additives that do not exhibit physiological activity on the skin, as long as the effects of the present invention are not impaired. An inactive substance can also be blended.

  Examples of the active substance include humectants, cell activators, anti-inflammatory agents, cell activators, wrinkle inhibitors and the like. These specific components are not particularly limited as long as they do not impair the effects of the present invention, and those used in skin external preparations (including pharmaceuticals, quasi drugs, and cosmetics) or those that will be used in the future. It can be arbitrarily selected from among them.

  Non-active substances (carriers or additives) include bases, solubilizers, dispersants, suspending agents, surfactants, thickeners, stabilizers (preservatives), pH adjusters, colorants, fragrances Etc. can be illustrated. One or more of these components can be appropriately selected and blended depending on the form (form) of the epidermal thickening agent described later.

  Here, as a base, water; hydrocarbons such as paraffin, liquid paraffin, gelled hydrocarbon, ozokerite, ceresin, petrolatum, hard fat, microcrystalline wax; glyceryl tri-2-ethylhexanoate (trioctanoin), etc. Trifatty acid glycerides; higher alcohols such as lauryl alcohol, cetyl alcohol, stearyl alcohol, cetostearyl alcohol, oleyl alcohol, isostearyl alcohol, 2-octyldodecanol, behenyl alcohol, 2-hexyldecanol; lauric acid, myristic acid, palmitic acid, stearin Fatty acids such as acids, behenic acid, isostearic acid, oleic acid, linoleic acid and their esters; highly polymerized methylpolysiloxane, dimethylpolysiloxane, dimethylsiloxane Chill (polyoxyethylene) siloxane / methyl (polyoxypropylene) siloxane copolymer, dimethylsiloxane / methyl (polyoxyethylene) siloxane copolymer, dimethylsiloxane / methyl (polyoxypropylene) siloxane copolymer, polyoxyethylene・ Methyl polysiloxane copolymer, poly (oxyethylene / oxypropylene) / methyl polysiloxane copolymer, dimethyl siloxane / methyl cetyloxy siloxane copolymer, dimethyl siloxane / methyl stearoxy siloxane copolymer, alkyl acrylate copolymer Polymer methylpolysiloxane ester, crosslinked methylpolysiloxane, crosslinked methylphenylpolysiloxane, crosslinked polyether-modified silicone, crosslinked alkylpolyether-modified silicone, crosslinked Polymerized silicones (silicone resins) such as alkylated silicones; ethylene glycol monoacetate, ethylene glycol diacetate, triethylene glycol diacetate, hexylene glycol diacetate, and 2-methyl-2-propene-1, Acetic acid glycol such as 1-diol diacetate; Triethylene glycol divalerate, 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate, 2,2,4-trimethyl-1,3-pentane Glycol esters such as diol diisobutyrate; ethylene glycol diacrylate, diethylene glycol diacrylate, propylene glycol monoacrylate, 2,2-dimethyl-trimethylene glycol diacrylate, 1,3-butylene glycol diacrylate, etc. Glycol acrylate; ethylene glycol Glycol dinitrates such as dinitrate, diethylene glycol dinitrate, triethylene glycol dinitrate, and propylene glycol dinitrate; 2,2 '-[1,4-phenylenedioxy] diethanol, dioxane, butylene glycol adipic acid polyester, etc. Can do. Preferably, it is an aqueous base for preparing an ointment, and examples thereof include water, paraline, liquid paraffin, silicone resin, cetyl alcohol, stearyl alcohol, and glycols, but are not limited thereto.

  Surfactants include glyceryl fatty acids such as glyceryl monostearate and glyceryl monostearate; polyglyceryl fatty acids such as polyglyceryl monoisostearate and polyglyceryl diisostearate; sorbitan monoisostearate, sorbitan monolaurate, sorbitan Sorbitan fatty acid esters such as monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexylate, diglycerol sorbitan tetra-2-ethylhexylate; propylene glycol fatty acid esters such as propylene glycol monostearate; polyoxy Ethylene hardened castor oil 40, polyoxyethylene hardened castor oil 50, polyoxyethylene hardened castor oil 60, polyoxyethylene hardened castor oil 80 Hardened castor oil derivatives: polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), polyoxyethylene (20) sorbitan monostearate (polysorbate 60), polyoxyethylene (20) sorbitan monooleate (polysorbate 80) Other examples include polyoxyethylene sorbitan fatty acid esters (polysorbates) such as polyoxyethylene monococonut oil fatty acid glyceryl, glycerin alkyl ether, alkyl glucoside, polyoxyethylene cetyl ether, stearylamine, and oleylamine. Preferably, surfactants used in the preparation of ointments, such as sorbitan monostearate, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene (20) sorbitan monostearate, etc. It can mention, but it is not limited to these.

  Examples of the thickener include celluloses such as methylcellulose, ethylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose; alginic acids such as sodium alginate and propylene glycol alginate; guar gum, locust bean gum, carrageenan , Gums such as xanthan gum; dextran, polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl methyl ether, carboxyvinyl polymer, alkyl acrylate copolymer, sodium polyacrylate, polyethylene glycol, bentonite, dextrin fatty acid ester, pectin, etc. Can be mentioned. Preferably, it is a thickener used for preparing an ointment.

  Stabilizers (preservatives) include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, butyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, paraoxybenzoate Examples thereof include benzyl acid, methyl paraoxybenzoate, phenoxyethanol, 1,2-hexanediol, and sodium edetate.

  pH adjusters include inorganic acids (hydrochloric acid, sulfuric acid, phosphoric acid, polyphosphoric acid, boric acid, etc.), organic acids (lactic acid, acetic acid, citric acid, tartaric acid, malic acid, succinic acid, sodium succinate, oxalic acid, glucone) Acid, fumaric acid, propionic acid, acetic acid, aspartic acid, epsilon-aminocaproic acid, glutamic acid, aminoethylsulfonic acid, etc.), gluconolactone, ammonium acetate, inorganic base (sodium bicarbonate, sodium carbonate, potassium hydroxide, hydroxide) Sodium, calcium hydroxide, magnesium hydroxide, etc.) and organic bases (monoethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, lysine, etc.).

  The external preparation for skin of the present invention can be prepared in various forms.

  For example, when the external preparation for skin is an external medicine or quasi-drug, it is a solution (lotion, suspension, emulsion, aerosol), ointment, cream, gel (gel), patch A form etc. can be illustrated. Ointments, creams and gels are preferred, and ointments are more preferred. The topical medicine or quasi-drug is a preparation that promotes skin wound healing by promoting the proliferation of keratinocytes in the epidermis and thickening the epidermis. It is effective as a therapeutic agent for keratosis) and a therapeutic agent for acne (comedo).

  Moreover, when skin external preparations are cosmetics or external quasi-drugs (medicinal cosmetics), but are not limited, for example, basic cosmetics such as lotions, emulsions, creams, lotions, oils and packs; foundations Makeup cosmetics such as blusher and white powder; skin cleansing agents such as facial cleansers, cleansing and body cleaning agents; massage agents, wiping agents; detergents;

  According to the cosmetics or quasi-drugs for external use (medicinal cosmetics), the proliferation of keratinocytes in the epidermis is promoted and the thickening of the epidermis is promoted, so that the skin tension and elasticity are improved and fine lines are noticeable. It can be expected to have an effect of refining the skin, preventing skin aging and preventing skin aging.

  The external preparation for skin of the present invention can be prepared in the various preparation forms described above according to the purpose and applied to the skin. The application amount can be appropriately set according to the age of the patient, the form of the preparation, the degree of skin symptoms, and the administration method (application or pack). For example, in terms of the amount of retinoid contained in the external preparation for skin, the amount applied once is usually about 0.003 to 15 mg, preferably about 0.03 to 9 mg, more preferably 0.3 to 3 mg. Degree. It can be applied once to several times a day.

  In addition, it is preferable to use the skin external preparation of this invention continuously in order to exhibit the effect effectively. For example, it is recommended to use it continuously for at least 1 week or more, more preferably for 2 weeks or more.

  Hereinafter, the configuration of the present invention and the effects thereof will be described using experimental examples. However, this invention is not restrict | limited at all by this Example.

Experimental example 1
1. experimental method
1-1. Preparation of test sample The ingredients described in Table 1 are mixed according to a conventional method to prepare an ointment ( Reference Examples 1 and 2, Examples, Control Examples), and this is used as a test sample for measuring the thickness of the epidermis described below. did.

1-2. Measurement of epidermal thickening The test samples prepared above ( Reference Examples 1 and 2, Examples, Control Examples) were placed on the back skin of hairless mice (HR-1) (n = 1) for 4 weeks (months). -Friday, once a day) After application, the skin tissue was peeled off, and the peel thickness was measured for the peeled skin tissue according to the following method.

  First, the collected mouse skin tissue was fixed in formalin and embedded in paraffin. Thereafter, a section was prepared by slicing the tissue to a thickness of 4 μm, and then stained with hematoxylin and eosin (HE staining). Subsequently, the stained tissue sections were observed and photographed using an optical microscope (BX51, OLYMPUS / AxioCam MRc, ZEISS). For the analysis of the epidermis thickening, the thickness of the epidermis was measured from the tissue-stained image taken at a magnification of 200 using image analysis software (AxioVision, ZEISS). The thickness of the epidermis was measured at three locations for each field of view (one image), and the operation was similarly performed in 10 fields of view. The average value of the thicknesses of a total of 30 locations measured from one tissue section was taken as the epidermis thickening degree (μm).

2. The experimental results are shown in Table 2. Table 2 shows the epidermis thickening degree (average value) obtained when the test samples of Reference Examples 1 and 2 and Examples are applied, and the average value (41.0 μm) of the epidermal thickening degree by the test sample of the control example. The value calculated as% (increase rate of epidermal thickening) is also shown. Moreover, the dyeing | staining image of the skin tissue which apply | coated the test sample of Example 3 and a control example is shown in FIG. 1 (A: Example, B: Control example).

From this result, by using retinol or a derivative thereof together with tocopherol or a derivative thereof, it is possible to promote the proliferation of epidermal keratinocytes and promote the thickening of the epidermis ( Reference Example 1), and the epidermis due to these components. It can be seen that the thickening promoting action is further enhanced by further using urea ( Reference Example 2) or glycyrrhizic acid or a salt thereof ( Example) . That is, this is because the combination of retinol or a derivative thereof and tocopherol or a derivative thereof is effective as an epidermal thickening promoter, and further, a combination of urea and / or glycyrrhizic acid or a salt thereof, particularly glycyrrhizin A combination of acids or salts thereof means that it is more effective as an epidermal thickening promoter.

Claims (4)

(A) retinoid, (B) tocopherol, or tocopherol organic acid ester or salt thereof (excluding tocopheryl retinoate), and (C) glycyrrhizic acid or salt thereof as an active ingredient An epidermal thickening promoter,
The epidermis thickening promoter is prepared as an external preparation for skin , the proportion of component (A) in the external preparation for skin is 0.001 to 5 wt%, the proportion of component (B) is 1 to 5 wt% , and component (C) Is an epidermis thickening promoter having a ratio of 0.1 to 12% by weight . (A) above acanthosis promoting agent according to claim 1 Symbol mounting a retinoid retinol fatty acid ester. The epidermal thickening promoter according to claim 1 or 2 , wherein the component (B) is a tocopherol organic acid ester (excluding tocopheryl retinoate). The ratio of the component (A) is 0.001 to 5% by weight, the ratio of the component (B) is 1 to 5% by weight , and the ratio of the component (C) is 0.1 to 12% by weight. A skin external preparation having an epidermal thickening promoting action, comprising the epidermal thickening promoter described in any one of 3 above.

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