Skin penetration enhancer

Abstract

To provide a novel skin penetration enhancer capable of enhancing penetration of a physiologically active substance into skin.SOLUTION: A skin penetration enhancer for a physiologically active substance is provided which comprises a compound represented by chemical formula (1) in the figure. The physiologically active substance is selected from ascorbic acid, salts thereof and derivatives thereof, and can be used in cosmetics, quasi-drugs or drugs.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a skin penetration enhancer that can promote the penetration of bioactive substances into the skin.

Background Art

[0002] In pharmaceuticals, quasi-drugs, cosmetics, etc. containing bioactive substances for the skin such as whitening agents, anti-aging agents, blood circulation promoters, vitamins, amino acids, wound healing promoters, irritation relievers, analgesics, cell activators, enzyme components, etc., a skin penetration enhancer is usually formulated to promote the penetration of the formulated bioactive substances into the skin.

[0003] Examples of such skin penetration enhancers include, for example, the mixture of 1,2-octanediol described in Patent Document 1 and 1,2-pentanediol and / or 1,2-hexanediol, 3-methyl-1,3-butanediol described in Patent Document 2, the lipopeptide compound or its salt described in Patent Document 3, the sugar-modified linear silicone described in Patent Document 4, etc. However, even with these penetration enhancers, the effect of promoting the penetration of bioactive substances into the skin is not sufficient, and there has still been a demand for excellent skin penetration enhancers in the market.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Summary of the Invention

Problems to be Solved by the Invention

[0005] Accordingly, an object of the present invention is to provide a novel skin penetration enhancer that can promote the penetration of a physiologically active substance into the skin.

Means for Solving the Problems

[0006] Therefore, the present inventors have intensively studied and found that a specific compound can promote the penetration of a physiologically active substance into the skin, leading to the present invention. That is, the present invention is a skin penetration enhancer for a physiologically active substance, which comprises a compound represented by the following chemical formula (1).

[0007]

Chemical Formula

Effects of the Invention

[0008] According to the present invention, by using the compound represented by the chemical formula (1) in combination with a physiologically active substance, the penetration of the physiologically active substance into the skin can be promoted.

Modes for Carrying Out the Invention

[0009] Hereinafter, the present invention will be described in detail. The skin penetration enhancer of the present invention is a skin penetration enhancer for a physiologically active substance, which comprises a compound represented by the following chemical formula (1).

[0010]

Chemical Formula

[0011] The method for producing the compound represented by Chemical Formula (1) is not particularly limited, and any known method can be used. For example, a method of subjecting cycloalkanol and glycerin to a dehydration condensation reaction, a method of subjecting cyclohexyl chloride or cyclohexyl bromide and glycerin to a dehalogenation reaction, a method of subjecting cyclohexanol and 1-chloro-2,3-propanediol to a dehydrochlorination reaction, a method of reacting cyclohexanol and epichlorohydrin and then ring-opening the obtained cyclohexyl glycidyl ether, a method of reacting cyclohexanol and glycidol and then ring-opening the obtained cyclohexyl glycidyl ether, a method of subjecting cyclohexanol and allyl chloride to a dehydrochlorination reaction, oxidizing with hydrogen peroxide or the like, and then ring-opening the obtained cyclohexyl glycidyl ether, and the like can be mentioned. Further, in the reaction using glycerin, the above reaction can be carried out using a partially esterified product of glycerin with a lower fatty acid, and after the reaction is completed, saponification is carried out to remove the fatty acid, or the above reaction can be carried out using a partial ketalized product of glycerin, and after the reaction is completed, the ketal is removed, whereby a highly pure product can be obtained. Among these, from the viewpoints of low cost and easy industrial production, it is preferable to produce by a method of reacting cyclohexanol and epichlorohydrin and then ring-opening the obtained cyclohexyl glycidyl ether.

[0012] The physiologically active substance for which the skin penetration promoter of the present invention can promote penetration into the skin is not particularly limited as long as it is a substance having effective physiological activity against the skin, such as known whitening agents, anti-aging agents, blood circulation promoters, anti-inflammatory agents, wound healing promoters, analgesics, cell activators, vitamins, amino acids, enzyme components, etc. In the present invention, the skin is a concept that includes not only the body surface such as the face, head, neck, chest, abdomen, waist, back, buttocks, arms, legs, hands, etc., but also mucous membranes such as oral mucosa, nasal mucosa, and conjunctival mucosa.

[0013] In the present invention, the physiologically active substance specifically includes ascorbic acid, its salts or its derivatives (such as sodium ascorbyl phosphate, magnesium ascorbyl phosphate, ascorbic acid-2-glucoside, etc.), hydroquinone derivatives such as arbutin, tranexamic acid and its salts or derivatives, kojic acid and its salts or derivatives, placenta extract, whitening agents such as glutathione, coral grass extract, rice leaf extract, eggplant extract, catamenia extract, eelgrass extract, rice extract, germinated rice extract, germinated rice ferment, black soybean extract, gentiana extract, licorice extract, carrot extract, aloe extract, sea mustard extract, red algae extract, beech extract, aloe vera extract, mannen wax extract, ginkgo extract, Japanese pampas grass extract, safflower extract, ota nenjin extract, western maidenhair fern extract, hagoromo grass extract, lotus extract, mango extract, mangosteen extract, yeast extract, animal-derived collagen, fish-derived collagen, elastin, intercellular lipid, glycyrrhizic acid, t-cycloamino acid derivative, diisopropylamine dichloroacetate, γ-amino-β-hydroxybutyric acid, coenzyme Q-10, α-lipoic acid, ergothioneine, allantoin, diisopropylamine dichloroacetate, eggshell membrane extracted protein, potassium deoxyribonucleic acid salt, pollen load extract, and anti-aging agents such as their salts or derivatives, zingerone, cantharis tincture, ichthyol, tannic acid, α-borneol, inositol hexanicotinate, cyclandelate, cinnarizine, triazolamine, acetylcholine, verapamil, nonylic acid valeryl amide, assemblage extract, cephalanthin, oryzanol, capsicum tincture, ginger tincture, cantharis tincture, benzyl nicotinate, tocopherol nicotinate, β-butoxyethyl nicotinate and other blood circulation promoters, glycyrrhizic acid, glycyrrhetinic acid, allantoin, azulenes, salicylic acid, hinokitiol, indomethacin, felbinac, diclofenac sodium, loxoprofen sodium, tranexamic acid, thiotaurine, hypotaurine, their salts or their derivatives and other anti-inflammatory agents, retinol, fusidic acid, and their derivatives and other wound healing promoters, glycol salicylate, methyl salicylate, amino benzoate, camphor, pramoxine,Analgesics such as lidocaine, capsaicin, isobutyl propanoic phenolic acid, DNA, placenta extract, chlorella extract, bilberry leaf extract, aloe extract, kakkon extract, chlorella extract, placenta extract, maple sap, royal jelly, yeast extract, mucopolysaccharide body fluid, hawthorn extract, soybean extract, whey, photoreceptor, cell activators such as cholesterol derivatives, vitamins such as vitamin A, vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin B9, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, salts or derivatives thereof, aliphatic amino acids, branched-chain amino acids, hydroxy amino acids, sulfur-containing amino acids, amide-type amino acids, imino acids, aromatic amino acids, aspartic acid, glutamic acid, lysine, arginine, histidine, hydroxyproline, hydroxylysine, tranexamic acid, dihydroxyphenylalanine, theanine, γ-aminobutyric acid, β-alanine, sarcosine, citrulline, ornithine, ε-aminocaproic acid, salts or derivatives thereof, amino acids, enzyme components such as trypsin, lysozyme chloride, chymotrypsin, semi-alkali protease, serrapeptase, lipase, hyaluronidase, etc. are represented.

[0014] In the present invention, it is preferable that the physiologically active substance is selected from ascorbic acid, its salts or its derivatives, and it is more preferable to use ascorbyl phosphate salts such as sodium ascorbyl phosphate and magnesium ascorbyl phosphate. That is, in the present invention, the compound represented by the chemical formula (1) is preferably used as a skin penetration enhancer that promotes the penetration of ascorbic acid, its salts or its derivatives into the skin, and it is more preferable to use it as a skin penetration enhancer that promotes the penetration of ascorbyl phosphate salts such as sodium ascorbyl phosphate and magnesium ascorbyl phosphate into the skin.

[0015] The skin penetration enhancer of the present invention can be used, for example, by adding it to cosmetics, quasi-drugs, pharmaceuticals, etc. Here, "cosmetics", "quasi-drugs", and "drugs" shall be deemed to be those equivalent to "cosmetics", "quasi-drugs", and "drugs" as defined in Article 2 of the "Act on Securing Quality, Efficacy, and Safety of Pharmaceuticals, Medical Devices, etc." in Japan. Furthermore, the "quasi-drugs" and "drugs" of the present invention can also be used for humans and animals other than humans (such as dogs and cats).

[0016] At this time, the dosage forms of cosmetics, quasi-drugs, drugs, etc. are not particularly limited, and they can be used in dosage forms such as aqueous solution systems, solubilized systems, emulsified systems, powder systems, powder dispersion systems, oil liquid systems, gel systems, ointment systems, aerosol systems, etc. In the present invention, by adding a skin penetration enhancer composed of the compound represented by Chemical Formula (1) to a cosmetic, quasi-drug, or drug containing at least one physiologically active substance, the penetration of the physiologically active substance in the cosmetic, quasi-drug, or drug into the skin can be promoted. Among these, from the perspective of the effect of promoting the penetration of the physiologically active substance into the skin, it is preferable to add it to cosmetics, quasi-drugs, and drugs such as creams, lotions, gels, emulsions, liquids, patches, aerosols, ointments, packs, etc. At this time, from the perspective of the effect of the present invention, it is preferable to use a cosmetic, quasi-drug, or drug containing ascorbic acid and its salts or derivatives as the physiologically active substance, and it is preferable to use a cosmetic, quasi-drug, or drug containing ascorbyl phosphate salts such as sodium ascorbyl phosphate and magnesium ascorbyl phosphate as the physiologically active substance.

[0017] From the perspective of the effect of promoting the penetration of the physiologically active substance into the skin, it is preferable to add the compound represented by Chemical Formula (1) in an amount of 0.01 to 20% by mass, more preferably 0.02 to 10.0% by mass, and even more preferably 0.03 to 5.0% by mass, based on the total amount of the cosmetic, quasi-drug, and drug.

[0018] The cosmetic, quasi-drug, or pharmaceutical of the present invention is a cosmetic, quasi-drug, or pharmaceutical containing a skin penetration enhancer composed of a compound represented by chemical formula (1) and a physiologically active substance. Examples of the physiologically active substance at this time include the aforementioned physiologically active substances. From the viewpoint of the effect of promoting the penetration of the physiologically active substance into the skin by the skin penetration enhancer composed of the compound represented by chemical formula (1), the content of the skin penetration enhancer composed of the compound represented by chemical formula (1) in the cosmetic, quasi-drug, or pharmaceutical is 0.01% by mass to 20% by mass based on the total amount of the cosmetic, quasi-drug, or pharmaceutical, and the content of the physiologically active substance is preferably 0.001% by mass to 10% by mass based on the total amount of the cosmetic, quasi-drug, or pharmaceutical. At this time, when the cosmetic, quasi-drug, or pharmaceutical contains two or more kinds of physiologically active substances, the content of the physiologically active substance in the cosmetic, quasi-drug, or pharmaceutical represents the total amount of the contents of the respective physiologically active substances. The content of the skin penetration enhancer composed of the compound represented by chemical formula (1) in the cosmetic, quasi-drug, or pharmaceutical is more preferably 0.02 to 10.0% by mass, and even more preferably 0.03 to 5.0% by mass based on the total amount of the cosmetic, quasi-drug, or pharmaceutical. Further, the content of the physiologically active substance in the cosmetic, quasi-drug, or pharmaceutical is more preferably 0.01% by mass to 5% by mass, and even more preferably 0.1 to 3% by mass based on the total amount of the cosmetic, quasi-drug, or pharmaceutical.

[0019] The ratio of the content of the skin penetration enhancer composed of the compound represented by chemical formula (1) to the physiologically active substance in the cosmetic, quasi-drug, or pharmaceutical of the present invention is not limited and can be appropriately adjusted according to the purpose. However, from the viewpoint of the effect of promoting the penetration of the physiologically active substance into the skin by the skin penetration enhancer composed of the compound represented by chemical formula (1), the ratio of the content of the skin penetration enhancer composed of the compound represented by chemical formula (1) to the physiologically active substance (the total amount in the case of two or more kinds) in the cosmetic, quasi-drug, or pharmaceutical is preferably 1:99 to 99.9:0.1 by mass ratio, and more preferably 10:90 to 99:1.

[0020] In the present invention, it is preferable that the cosmetic, quasi-drug, or pharmaceutical of the present invention contains one or more selected from ascorbic acid, its salts, or its derivatives as a physiologically active substance. More preferably, it contains an ascorbyl phosphate salt such as sodium ascorbyl phosphate or magnesium ascorbyl phosphate as a physiologically active substance. Specifically, it is even more preferable that an ascorbyl phosphate salt such as sodium ascorbyl phosphate or magnesium ascorbyl phosphate is contained in an amount of 0.01% by mass to 5% by mass based on the total amount of the cosmetic, quasi-drug, or pharmaceutical, and particularly preferably, it is contained in an amount of 0.1% to 3% by mass. At this time, the ratio of the skin penetration enhancer composed of the compound represented by the chemical formula (1) in the cosmetic, quasi-drug, or pharmaceutical to the content of the ascorbyl phosphate salt such as sodium ascorbyl phosphate or magnesium ascorbyl phosphate as a physiologically active substance is preferably 1:99 to 99.9:0.1 by mass ratio, and more preferably 10:90 to 99:1.

[0021] The cosmetic, quasi-drug, or pharmaceutical of the present invention can further contain components used in each application in order to improve and modify various properties (solubility, dispersibility, stability, usability, spreadability, penetrability, moisturizing property, safety, design property, optical property, aromatic property, etc.) during storage, use, and after use according to the purpose of use and application. Examples of such components include solvents, cationic surfactants, anionic surfactants, amphoteric surfactants, nonionic surfactants, hydrocarbon oils, silicone oils, ester oils, higher alcohols, polyhydric alcohols, saccharides and their derivatives, moisturizing agents, preservatives, sequestering agents, pH adjusters, fragrances, etc., and one or more of these can be contained.

[0022] Examples of the solvent include ethanol, isopropyl alcohol, butanol, isobutyl alcohol, acetone, ethyl acetate, ethylene glycol monoethyl ether, water, etc., and one or more of these can be used. The content of the solvent in the cosmetics, quasi-drugs, or pharmaceuticals of the present invention is not particularly limited, but for example, it is preferably 10% by mass to 99% by mass, and more preferably 20% by mass to 95% by mass, based on the total amount of the cosmetics, quasi-drugs, or pharmaceuticals.

[0023] Examples of the cationic surfactant include lauryl trimethyl ammonium chloride, cetyl trimethyl ammonium chloride, stearyl trimethyl ammonium chloride, alkyl trimethyl ammonium chloride, distearyl dimethyl ammonium chloride, stearyl trimethyl ammonium saccharin, cetyl trimethyl ammonium saccharin, behenyl trimethyl ammonium methyl sulfate, behenyldimethylamine, diethylaminoethyl amide behenate, dimethylaminopropyl amide behenate, dimethylaminoethyl amide behenate, stearyldimethylamine, palmityloxypropyl dimethylamine, stearyloxypropyl dimethylamine, etc., and one or more of these can be used. The content of the cationic surfactant in the cosmetics, quasi-drugs, or pharmaceuticals of the present invention is not particularly limited, but for example, it is preferably 0.001% by mass to 10% by mass, and more preferably 0.01% by mass to 5% by mass, based on the total amount of the cosmetics, quasi-drugs, or pharmaceuticals.

[0024] Examples of anionic surfactants include alkyl ether sulfates, alkyl sulfates, alkyl ether sulfate esters, alkenyl ether sulfates, alkenyl sulfates, olefin sulfonates, alkane sulfonates, saturated or unsaturated fatty acid salts, alkyl or alkenyl ether carboxylates, α-sulfonated fatty acid salts, N-acyl amino acid type surfactants, phosphoric acid mono- or diester type surfactants, sulfosuccinic acid esters, N-alkyloyl methyl taurine salts, and their derivatives, etc. One or more of these can be used. Specific examples of counterions for anionic groups include, for example, sodium ions, potassium ions, triethanolamine, etc. One or more of these can be used. The content of the anionic surfactant in the cosmetics, quasi-drugs, or pharmaceuticals of the present invention is not particularly limited, but for example, it is preferably 0.001% by mass to 10% by mass, more preferably 0.01% by mass to 5% by mass, based on the total amount of the cosmetics, quasi-drugs, or pharmaceuticals.

[0025] Examples of amphoteric surfactants include betaine type amphoteric surfactants such as coconut oil fatty acid amide propyl dimethyl acetic acid betaine, lauryl dimethyl amino acid betaine, 2-alkyl-N-carboxymethyl-N-hydroxymethyl imidazolinium betaine, lauryl hydroxy sulfobetaine, lauroyl amide ethyl hydroxyethyl carboxymethyl betaine, and metal salts of hydroxypropyl phosphoric acid; amino acid type amphoteric surfactants such as metal salts of β-lauryl aminopropionic acid; sulfate ester type amphoteric surfactants; and sulfonate type amphoteric surfactants, etc. One or more of these can be used. The content of the amphoteric surfactant in the cosmetics, quasi-drugs, or pharmaceuticals of the present invention is not particularly limited, but for example, it is preferably 0.001% by mass to 10% by mass, more preferably 0.01% by mass to 5% by mass, based on the total amount of the cosmetics, quasi-drugs, or pharmaceuticals.

[0026] Examples of nonionic surfactants include POE cetyl ether (Ceteth), POE stearyl ether (Steareth), POE behenyl ether, POE oleyl ether (Oleth), POE lauryl ether (Laureth), POE octyldodecyl ether, POE hexyl decyl ether, POE isostearyl ether, POE nonyl phenyl ether, POE octyl phenyl ether, POE polyoxypropylene cetyl ether, POE polyoxypropylene decyl tetradecyl ether, POE sorbitan monooleate, POE sorbitan monostearate, POE sorbitan monopalmitate, POE sorbitan monolaurate, POE sorbitan trioleate, POE glycerin monostearate, POE glycerin monomyristate, POE sorbitol tetraoleate, POE sorbitol hexastearate, POE sorbitan monolaurate, POE sorbitol beeswax, polyethylene glycol monooleate, polyethylene glycol monostearate, polyethylene glycol monolaurate, lipophilic glycerin monooleate, lipophilic glycerin monostearate, self-emulsifying glycerin monostearate, sorbitan monooleate, sorbitan sesquioleate, sorbitan trioleate, sorbitan monostearate, sorbitan monopalmitate, sorbitan monolaurate, sucrose fatty acid ester, decaglyceryl monolaurate, decaglyceryl monostearate, decaglyceryl monooleate, decaglyceryl monomyristate, alkyl glucoside, POE methyl glucoside, POE methyl glucoside dioleate, etc. One or more of these can be used. The content of the nonionic surfactant in the cosmetics, quasi-drugs, or pharmaceuticals of the present invention is not particularly limited, but for example, it is preferably 0.001% by mass to 10% by mass, more preferably 0.01% by mass to 5% by mass, based on the total amount of the cosmetics, quasi-drugs, or pharmaceuticals.

[0027] Examples of hydrocarbon oils include liquid paraffin, squalane, pristane, ozokerite, paraffin, ceresin, petrolatum, polyisobutene, polyisoprene, isodecane, isododecane, isohexadecane, normal pentane, isopentane, normal hexane, isohexane, kerosene, decalin, tetralin, microcrystalline wax, etc. One or more of these can be used. The content of hydrocarbon oil in the cosmetics, quasi-drugs, or pharmaceuticals of the present invention is not particularly limited, but for example, it is preferably 0.1% by mass to 50% by mass, more preferably 0.5% by mass to 30% by mass, based on the total amount of the cosmetics, quasi-drugs, or pharmaceuticals.

[0028] Examples of silicone oils include chain silicone oils such as dimethylpolysiloxane, diphenylpolysiloxane, diphenylsiloxyphenyltrimethicone, octamethyltrisiloxane, etc., cyclic silicone oils such as decamethylcyclotetrasiloxane, dodecamethylcyclotetrasiloxane, octamethylcyclotetrasiloxane, cyclopentasiloxane, dodecamethylcyclopentasiloxane, octamethylcyclopentasiloxane, decamethylcyclohexasiloxane, dodecamethylcyclohexasiloxane, octamethylcyclohexasiloxane, etc., and modified silicone oils such as alkyl-modified dimethylpolysiloxane, polyether-modified dimethylpolysiloxane, fatty acid-modified polysiloxane, higher alcohol-modified polysiloxane, amino-modified polysiloxane, fluorine-modified polysiloxane, etc. One or more of these can be used. The content of silicone oil in the cosmetics, quasi-drugs, or pharmaceuticals of the present invention is not particularly limited, but for example, it is preferably 0.1% by mass to 50% by mass, more preferably 0.5% by mass to 30% by mass, based on the total amount of the cosmetics, quasi-drugs, or pharmaceuticals.

[0029] Examples of ester oils include ethyl acetate, butyl acetate, hexyl acetate, decyl acetate, butyl propionate, cetyl octanoate, hexyl decyl dimethyl octanoate, isononyl isononanoate, isononyl isononanoate, isotridecyl isononanoate, ethyl laurate, hexyl laurate, myristyl myristate, isopropyl myristate, isopropyl palmitate, 2-ethylhexyl palmitate, 2-hexyldecyl palmitate, 2-heptylundecyl palmitate, decyl oleate, oleyl oleate, octyldodecyl oleate, isocetyl stearate, glyceryl stearate, butyl stearate, 2-ethylhexyl hydroxystearate, ethylene glycol stearate, octyl oxystearate, diethyl phthalate, triethyl citrate, 2-ethylhexyl succinate, diisopropyl sebacate, di-2-ethylhexyl sebacate, cetyl lactate, myristyl lactate, diisobutyl adipate, 2-hexyldecyl adipate, di-2-heptylundecyl adipate, cetyl ethylhexanoate, triethyl hexanoin, polyglyceryl-2 triisostearate, neopentyl glycol dioctanoate, neopentyl glycol dicaprate, pentaerythrityl tetraisostearate and other synthetic ester oils; lanolin, mink oil, cocoa butter, coconut oil, palm kernel oil, camellia oil, sesame oil, castor oil, olive oil and other animal and vegetable ester oils. One or more of these can be used. The content of the ester oil in the cosmetics, quasi-drugs, or pharmaceuticals of the present invention is not particularly limited, but for example, it is preferably 0.1% by mass to 50% by mass, more preferably 0.5% by mass to 30% by mass, based on the total amount of the cosmetics, quasi-drugs, or pharmaceuticals.

[0030] Examples of the higher alcohols include cetyl alcohol, isostearyl alcohol, lauryl alcohol, hexadecyl alcohol, octyldodecanol, etc., and one or more of these can be used. The content of the higher alcohol in the cosmetics, quasi-drugs, or pharmaceuticals of the present invention is not particularly limited, but for example, it is preferably 0.1% by mass to 30% by mass, more preferably 0.5% by mass to 20% by mass, based on the total amount of the cosmetics, quasi-drugs, or pharmaceuticals.

[0031] Examples of the polyhydric alcohols include ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, highly polymerized polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, isoprene glycol, 1,3-butylene glycol, glycerin, diglycerin, polyglycerin, etc., and one or more of these can be used. The content of the polyhydric alcohol in the cosmetics, quasi-drugs, or pharmaceuticals of the present invention is not particularly limited, but for example, it is preferably 0.1% by mass to 30% by mass, more preferably 0.5% by mass to 20% by mass, based on the total amount of the cosmetics, quasi-drugs, or pharmaceuticals. However, the compound represented by the chemical formula (1) is excluded from the polyhydric alcohols.

[0032] Examples of the saccharides and their derivatives include xylose, D-glucose, sucrose, trehalose, fructose, maltose, mannose, cyclodextrin, β-glucan, chitin, chitosan, pectin, arabinogalactan, dextrin, dextran, glucosylethyl methacrylate polymer or copolymer, etc., and one or more of these can be used. The content of the saccharides and their derivatives in the cosmetics, quasi-drugs, or pharmaceuticals of the present invention is not particularly limited, but for example, it is preferably 0.001% by mass to 10% by mass, more preferably 0.01% by mass to 5% by mass, based on the total amount of the cosmetics, quasi-drugs, or pharmaceuticals.

[0033] Examples of the humectant include polyethylene glycol, xylitol, sorbitol, maltitol, chondroitin sulfate, hyaluronic acid, mucitin sulfate, caronic acid, atelocollagen, cholesteryl-12-hydroxystearate, sodium lactate, bile salt, dl-pyrrolidone carboxylate, short-chain soluble collagen, Rosa multiflora Thunb. extract, Viola arvensis Murray extract, Melilotus officinalis extract, and the like. The content of the humectant in the cosmetics, quasi-drugs, or pharmaceuticals of the present invention is not particularly limited, but for example, it is preferably 0.01% by mass to 30% by mass, more preferably 0.1% by mass to 20% by mass, based on the total amount of the cosmetics, quasi-drugs, or pharmaceuticals.

[0034] Examples of the preservative include benzoic acid, salicylic acid, phenol, sorbic acid, potassium sorbate, paraoxybenzoic acid ester, sodium benzoate, parachlorometacresol, hexachlorophene, benzalkonium chloride, chlorhexidine chloride, trichlorocarbanilide, photosensitizer, chlorphenesin, phenoxyethanol, methylparaben, ethylparaben, butylparaben, caprylyl glycol, resorcinol, triclosan, isopropylmethylphenol (IPMP), zinc bis(2-pyridylthio-1-oxide), alkyl diminoethyl glycine hydrochloride, piroctone olamine, hinokitiol, vitamin B6 hydrochloride (pyridoxine hydrochloride), phenol, lysozyme chloride, cetylpyridinium chloride (CPC), and the like. The content of the preservative in the cosmetics, quasi-drugs, or pharmaceuticals of the present invention is not particularly limited, but for example, it is preferably 0.01% by mass to 10% by mass, more preferably 0.1% by mass to 5% by mass, based on the total amount of the cosmetics, quasi-drugs, or pharmaceuticals.

[0035] Examples of the metal ion sequestering agent include 1-hydroxyethane-1,1-diphosphonic acid, tetrasodium 1-hydroxyethane-1,1-diphosphonate, disodium edetate, trisodium edetate, tetrasodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, phosphoric acid, citric acid, succinic acid, edetic acid, trisodium ethylenediaminehydroxyethyltriacetate, etc. The content of the metal ion sequestering agent in the cosmetic, quasi-drug, or pharmaceutical of the present invention is not particularly limited, but for example, it is preferably 0.001% by mass to 5% by mass, more preferably 0.01% by mass to 3% by mass, based on the total amount of the cosmetic, quasi-drug, or pharmaceutical.

[0036] Examples of the pH adjuster include citric acid, glycolic acid, succinic acid, tartaric acid, lactic acid, malic acid, levulinic acid, acetic acid, butyric acid, valeric acid, oxalic acid, maleic acid, fumaric acid, mandelic acid, phosphoric acid, pyrophosphoric acid, hydrochloric acid, sulfuric acid, nitric acid, etc., and one or more of these can be used. The pH adjuster in the cosmetic, quasi-drug, or pharmaceutical of the present invention is preferably added so that the pH of the cosmetic, quasi-drug, or pharmaceutical becomes 3.0 to 13.0.

[0037] Examples of the fragrance include acetyl cedrene, allyl amyl glycolate, β-ionone, isobutyl quinoline, iris oil, iron, indole, undecanal, undecenal, γ-undecalactone, estragole, eugenol, oakmoss, opoponax resinoid, orange oil, eugenol, aurantiol, galaxolide, carvacrol, camphor, carrot seed oil, clove oil, methyl caffeate, geraniol, geranyl nitrile, isobornyl acetate, geranyl acetate, dimethyl benzyl carbinyl acetate, styrallyl acetate, cedryl acetate, terpinyl acetate, vetiveryl acetate, benzyl acetate, linalyl acetate, isopentyl salicylate, benzyl salicylate, sandalwood oil, santalol, cyclamen aldehyde, cyclopentadecanolide, methyl dihydrojasmonate, dihydromyrcenol, jasmine absolute, jasmine lactone, citral, citronellol, citronellal, cinnamon bark oil, styrax resinoid, cedarwood oil, cedrene, cedrol, celery seed oil, thyme oil, damascone, damasconone, thymol, tuberose absolute, terpineol, γ-terpinene, triplal, vanilla absolute, vanillin, basil oil, patchouli oil, hydroxycitronellal, α-pinene, piperitone, Peru balsam, vetiver oil, vetiverol, peppermint oil, pepper oil, heliotropin, bergamot oil, benzyl benzoate, borneol, myrrh resinoid, musk ketone, methyl nonyl acetaldehyde, γ-methyl ionone, menthol, L-menthol, L-menthone, eucalyptus oil, β-ionone, lime oil, lavender oil, D-limonene, linalool, lilial, lilyal, lemon oil, rose absolute, rose oxide, rose oil, rosemary oil, etc. One or more of these can be used. The content of the fragrance in the cosmetics, quasi-drugs, or pharmaceuticals of the present invention is not particularly limited, but for example, it is preferably 0.001% by mass to 5% by mass, more preferably 0.01% by mass to 3% by mass, based on the total amount of the cosmetics, quasi-drugs, or pharmaceuticals.

Examples

[0038] The present invention will be specifically described below with reference to examples. In the following examples and the like, % is based on mass unless otherwise specified.

[0039] <Preparation of Test Solutions 1 to 3> As test solutions, a compound represented by chemical formula (1) as a skin penetration enhancer and magnesium ascorbyl phosphate as a whitening agent as a physiologically active substance were added to phosphate buffered saline so that the content of the compound represented by chemical formula (1) in the test solution was 2% by mass and the content of magnesium ascorbyl phosphate was 1% by mass, thereby preparing Test Solution 1. Similarly, 1,2 - hexanediol as a skin penetration enhancer of the comparative example and magnesium ascorbyl phosphate were added to phosphate buffered saline so that the content of 1,2 - hexanediol in the test solution was 2% by mass and the content of magnesium ascorbyl phosphate was 1% by mass, thereby preparing Test Solution 2. Similarly, magnesium ascorbyl phosphate was added to phosphate buffered saline so that the content of magnesium ascorbyl phosphate in the test solution was 1% by mass, thereby preparing Test Solution 3.

[0040] <Evaluation of Skin Penetration Promoting Effect> After adding 2 ml of phosphate buffered saline as a receptor to each well of the 12-well plate, a three-dimensional cultured epidermal model (manufactured by EPISKIN, EpiSkin (registered trademark)-LM) that had been acclimated overnight in the medium was placed. Subsequently, 0.15 ml of test solutions 1 to 3 were each dropped from the stratum corneum side of the epidermal model, and then left standing at 37°C. After 3 hours and 6 hours, 0.20 ml of the receiver solution was collected and 0.20 ml of phosphate buffered saline was replenished, respectively. Similarly, 0.20 ml of the receiver solution was collected after 9 hours, and the content of magnesium ascorbyl phosphate in each receiver solution was quantified by HPLC, respectively, to calculate the permeation amount (μg) of magnesium ascorbyl phosphate after standing for each time. The above test was performed 3 times each, and the average value of the content of magnesium ascorbyl phosphate in each receiver solution at each test solution and standing time was taken as the permeation amount of magnesium ascorbyl phosphate. The results of each test are shown in Table 1. In Table 1, the test example using test solution 1 is denoted as Example 1, the test example using test solution 2 is denoted as Comparative Example 1, and the test example using test solution 3 is denoted as Comparative Example 2.

[0041]

Table 1

[0042] From the above results, it was found that the compound represented by Chemical Formula (1) significantly promoted the penetration of magnesium ascorbyl phosphate into the skin. On the other hand, in the example using 1,2-hexanediol as a penetration enhancer, although the permeation amount of magnesium ascorbyl phosphate was slightly increased compared to the case where no skin penetration enhancer was added, no significant difference was observed in the permeation amount. Therefore, it can be seen that the skin penetration enhancer composed of the compound represented by Chemical Formula (1) can promote the penetration of physiologically active substances in cosmetics, quasi-drugs, or pharmaceuticals into the skin.

Claims

1. A skin penetration enhancer for ascorbic acid or a salt thereof, which consists of a compound represented by the following chemical formula (1) (however, excluding a composition for forming a lipid membrane structure containing a hydrogenated phospholipid having an acid value of 5 mg KOH / g or more). 【Chemical 1】

2. A cosmetic, quasi-drug, or pharmaceutical containing the skin penetration enhancer according to Claim 1 and ascorbic acid or a salt thereof (however, excluding cosmetics, quasi-drugs, and pharmaceuticals containing a hydrogenated phospholipid having an acid value of 5 mg KOH / g or more).

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