JP2007332088A5 - - Google Patents

Description

In view of such a situation, the present inventors sought vesicle dispersion preparations capable of transdermal administration, and as a result of intensive research efforts, 1) α, ε-bis (γ-N- It has been found that such a system can be obtained by using (C10-C30) acylglutamyl) lysine and 2) a polymer or copolymer having a phosphorylcholine structure in combination, and the present invention has been completed. That is, the present invention is as follows.
(1) A skin external preparation containing 1) α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine and 2) a polymer or copolymer having a phosphorylcholine structure. (2) The acyl group having 10 to 30 carbon atoms constituting the α, ε-bis (γ-N- (10 to 30 carbon atoms) acylglutamyl) lysine is a lauroyl group. The skin external preparation as described in (1).
(3) polymers or copolymers having a phosphorylcholine structure, poly methacryloyloxyethyl phosphorylcholine, butyl methacrylate methacryloyloxyethyl phosphorylcholine Turkey lincomycin polymer, one or selected from stearyl methacrylate, methacryloyloxyethyl phosphorylcholine Turkey lincomycin polymers and salts thereof are 2 The external preparation for skin according to (1) or (2), characterized in that it is a species or more.
(4) The external preparation for skin according to any one of (1) to (3), further comprising ceramide and / or phospholipid.
(5) The external preparation for skin according to any one of (1) to (4) , which is a vesicle dispersion.
(6) The external preparation for skin according to (5), wherein one or more selected from the components shown in Group A below are contained in the dispersed vesicles.
(Group A) Ursolic acid and / or salt thereof, ester of ursolic acid, ester of N-acylated glutamic acid, ester of glycyrrhetinic acid, vitamin E, vitamin A, centrureidine and / or salt thereof, methyl ophio Pogonanone B and / or salt thereof, escin and / or salt thereof, betulinic acid and / or salt thereof, betulin, ubidecarenone, pyrroloquinoline quinone, α-lipoic acid and / or salt thereof

Formula 1 (wherein R 1 and R 2 each independently represents an alkyl group or alkenyl group having 9 to 29 carbon atoms)

Alpha by methods such as the, .epsilon.-bis (γ-N- (10~30 carbon atoms) acyl Guru Tamil) is lysine may be used to manufacture, alpha, .epsilon.-bis (γ-N- (10 carbon atoms ~ 30) Acylglutamyl) lysine already exists in the market, and such a commercial product can be purchased and used. As such a commercially available product, “Perisea L-30” (manufactured by Asahi Kasei Corporation) can be suitably exemplified. The α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine thus obtained has the property of easily forming a bilayer, and is strengthened by a bilayer such as ceramide described later. Along with the components, it has the property of forming a vesicle dispersion easily and stably. In order to exert such action, the skin external preparation is used in a total amount of one or more selected from α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine. It is preferable to contain 0.05% by mass, more preferably 0.1% by mass, and 10% by mass as an upper limit, and more preferably 5% by mass with respect to the total amount. This is because when the amount of such a component is too large, a vesicle dispersion system may not be formed. When the amount is too small, a bilayer film may not be formed, and a vesicle dispersion system may not be formed.

(3) The skin external preparation of this invention The skin external preparation of this invention contains the said essential component, It is characterized by the above-mentioned. The external preparation for skin of the present invention can be applied without particular limitation as long as it is administered externally to the skin. For example, cosmetics including quasi-drugs, pharmaceutical compositions for external use on skin, miscellaneous items for external use, etc. Can be suitably exemplified. In addition, the dosage form is not particularly limited and can be applied to lotions, emulsions, essences, creams, and the like. A vesicle dispersion system is preferable because the effects of the present invention can be enhanced. An oil-soluble active ingredient can also be carried inside the double membrane of such a vesicle. Examples of the active ingredient to be supported include ursolic acid and / or a salt thereof, an ester of ursolic acid, an ester of N-acylated glutamic acid, an ester of glycyrrhetinic acid, vitamin E, vitamin A, and center ureidine. And salts thereof, methylophiopogononone B and salts thereof, escin and salts thereof, betulinic acid and salts thereof, betulin, ubidecarenone, pyrroloquinoline quinone and α-lipoic acid and salts thereof The above can be suitably exemplified. The ursolic acid can also be extracted from a plant such as rosemary. Esterification should just follow a conventional method and can be obtained by making it react with an alkyl halide in presence of an alkali. Centaureidine can be obtained by extracting whole plant of Achillea millet with an organic solvent such as ethanol, liquid-liquid extraction of the extract with ethyl acetate and water, and fractionating the ethyl acetate layer. Methyl ophiopogononone B is obtained from Bacmondow in the same manner. In the same way, escin can be obtained from the fruits of horse chestnut. A similar procedure yields betulin from the bark of birch plants such as birch. Ubidecarenone, pyrroloquinoline quinone, commercially available as the cosmetics raw material for α- lipoic acid resides. These salts can be used without any particular limitation as long as they are used in skin external preparations, for example, alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as calcium salts and magnesium salts. Preferred examples include organic amine salts such as ammonium salt, triethylamine salt, triethanolamine salt, and monoethanolamine salt, and basic amino acid salts such as lysine salt and alginate. In order to load these onto a vesicle, it may be processed according to a conventional method. For example, it is dissolved in advance together with a phase containing α, ε-bis (γ-N- (10 to 30 carbon atoms) acylglutamyl) lysine, What is necessary is just to add to an aqueous support | carrier. The content of the oil-soluble active ingredient is preferably 1 to 100 μM, more preferably 2 to 20 μM. The percutaneous absorbability can be further enhanced by supporting the vesicle in the bilayer membrane. About the method of extracting an active ingredient from the said plant body, a manufacture example is shown below.

The external preparation for skin of the present invention can contain, in addition to such components, optional components that are usually used in external preparations for skin. Such optional ingredients include, for example, macadamia nut oil, avocado oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower oil, cottonseed oil, jojoba oil, coconut oil, palm oil, liquid lanolin, hydrogenated coconut oil Oil, wax, oil such as beeswax, canola wax, carnauba wax, ibotarou, lanolin, reduced lanolin, hard lanolin, jojoba wax, liquid paraffin, squalane, pristane, ozokerite, paraffin, ceresin, petrolatum , Hydrocarbons such as microcrystalline wax; higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, undecylenic acid; cetyl alcohol, stearyl alcohol, isostearyl Higher alcohols such as alcohol, behenyl alcohol, octyldodecanol, myristyl alcohol, cetostearyl alcohol; cetyl isooctanoate, isopropyl myristate, hexyldecyl isostearate, diisopropyl adipate, di-2-ethylhexyl sebacate, cetyl lactate, malic acid Diisostearyl, di-2-ethylhexanoic acid ethylene glycol, dicaprate neopentyl glycol, di-2-heptylundecanoic acid glycerin, tri-2-ethylhexanoic acid glycerin, tri-2-ethylhexanoic acid trimethylolpropane, tri Synthetic ester oils such as trimethylolpropane isostearate and pentane erythritol tetra-2-ethylhexanoate; dimethylpolysiloxane, methylphenylpoly Linear polysiloxanes such as oxane and diphenylpolysiloxane; cyclic polysiloxanes such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, and dodecamethylcyclohexanesiloxane; amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxane, Oil agents such as silicone oils such as modified polysiloxanes such as fluorine-modified polysiloxanes; Anionic surfactants such as fatty acid soap (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, triethanolamine ether of alkyl sulfates; Cationic surfactants such as stearyltrimethylammonium, benzalkonium chloride, laurylamine oxide; imidazoline-based amphoteric surfactants (2-cocoyl-2-imida Zolinium hydroxide-1-carboxyethyloxy disodium salt, etc.), betaine surfactants (alkyl betaine, amide betaine, sulfobetaine, etc.), and amphoteric surfactants such as acylmethyl taurine; sorbitan fatty acid esters (sorbitan) Monostearate, sorbitan sesquioleate, etc.), glycerin fatty acids (glyceryl monostearate, etc.), propylene glycol fatty acid esters (propylene glycol monostearate, etc.), hardened castor oil derivatives, glycerin alkyl ethers, POE sorbitan fatty acid esters (POE sorbitan monooleate, polyoxyethylene sorbitan monostearate, etc.), POE sorbite fatty acid esters (POE-
Sorbit monolaurate, etc.), POE glycerin fatty acid esters (POE-glycerol monoisostearate, etc.), POE fatty acid esters (polyethylene glycol monooleate, POE distearate, etc.), POE alkyl ethers (POE2-octyldodecyl ether, etc.) , POE alkylphenyl ethers (POE nonylphenyl ether, etc.), Pluronic types, POE / POP alkyl ethers (POE / POP2-decyltetradecyl ether, etc.), Tetronics, POE castor oil / hardened castor oil derivative (POE) Castor oil, POE hydrogenated castor oil, etc.), nonionic surfactants such as sucrose fatty acid ester, alkyl glucoside; moisturizing ingredients such as sodium pyrrolidone carboxylate, lactic acid, sodium lactate; surface treatment Mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, silicic anhydride (silica), aluminum oxide, barium sulfate and other powders; surface may be treated, bengara , Yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, bitumen, titanium oxide, zinc oxide inorganic pigments; surface treated pearlescent agents such as titanium mica, fish phosphorus foil, bismuth oxychloride Red 202, red 228, red 226, yellow 4, blue 404, yellow 5, red 505, red 230, red 223, orange 201, red 213 which may be raked No., Yellow No. 204, Yellow No. 203, Blue No. 1, Green No. 201, Purple No. 201, Red No. 204, etc .; polyethylene powder, polymethyl methacrylate, nylon End, organic powders such as organopolysiloxane elastomers; para-aminobenzoic acid UV absorbers; anthranilic acid UV absorbers; salicylic acid type ultraviolet absorbers; cinnamic acid-based ultraviolet absorbents; benzophenone ultraviolet absorbers; sugar-based ultraviolet Absorbers; UV absorbers such as 2- (2′-hydroxy-5′-t-octylphenyl) benzotriazole and 4-methoxy-4′-t-butyldibenzoylmethane; Lower alcohols such as ethanol and isopropanol Vitamin A or its derivatives, vitamin B ₆ hydrochloride, vitamin B ₆ tripalmitate, vitamin B ₆ dioctanoate, vitamin B ₂ or a derivative thereof, vitamin B ₁₂ such as vitamin B ₁₂ , vitamin B ₁₅ or a derivative thereof; vitamin H , Vitamins such as pantothenic acid, pantethine, etc .; phenoxyethanol, etc. Such as antimicrobial agents can be preferably exemplified.

Claims (6)

1) A skin external preparation containing α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine and 2) a polymer or copolymer having a phosphorylcholine structure. The said C10-30 acyl group which comprises the said (alpha), (epsilon) -bis ((gamma) -N- (C10-C30) acyl glutamyl) lysine is a lauroyl group, It is characterized by the above-mentioned. An external preparation for skin as described in 1. above. Polymers or copolymers having a phosphorylcholine structure, poly methacryloyloxyethyl phosphorylcholine, butyl methacrylate methacryloyloxyethyl phosphorylcholine Turkey lincomycin polymer, one selected from stearyl methacrylate, methacryloyloxyethyl phosphorylcholine Turkey lincomycin polymers and their salts or in two or more The external preparation for skin according to claim 1 or 2, wherein the preparation is external. Furthermore, ceramide and / or phospholipid are contained, The skin external preparation in any one of Claims 1-3 characterized by the above-mentioned. It is a vesicle dispersion system, The skin external preparation in any one of Claims 1-4 characterized by the above-mentioned. The skin external preparation according to claim 5, wherein the dispersed vesicle contains one or more selected from the components shown in Group A below.
(Group A) Ursolic acid and / or salt thereof, ester of ursolic acid, ester of N-acylated glutamic acid, ester of glycyrrhetinic acid, vitamin E, vitamin A, centrureidine and / or salt thereof, methyl ophio Pogonanone B and / or salt thereof, escin and / or salt thereof, betulinic acid and / or salt thereof, betulin, ubidecarenone, pyrroloquinoline quinone, α-lipoic acid and / or salt thereof